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ADVANCES IN

Otolaryngology—Head
and Neck Surgery®
VOLUME 12
ADVANCES IN
Otolaryngology—Head
and Neck Surgery®
VOLUME 12

Editor-in-Chief
Eugene N. Myers, M.D.
Professor and Chairman, Department of Otolaryngology, University of
Pittsburgh School of Medicine, Pittsburgh, Pennsylvania

Associate Editor
Charles D. Bluestone, M.D.
Eberly Professor of Pediatric Otolaryngology, University of Pittsburgh
School of Medicine; Director, Department of Pediatric Otolaryngology,
Children's Hospital of Pittsburgh. Pittsburgh, Pennsylvania

Editorial Board
Derald E. Brackmann, M.D.
Clinical Professor of Otolaryngology and Neurosurgery, University of
Southern California School of Medicine; President, House Ear Clinic;
Board of Directors, House Ear Institute, Los Angeles, California

Charles J. Krause, M.D.


Professor, Department of Otolaryngology, University of Michigan School
of Medicine, Ann Arbor, Michigan

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Preface

T h e E d i t o r i a l B o a r d o f Advances in Otolaryngology—Head and


Neck Surgery i s v e r y p r o u d o f t h e g r e a t b r e a d t h a n d d e p t h o f
the content of this v o l u m e , w h i c h has b e e n p r e p a r e d by a very dis-
tinguished group of authors. This v o l u m e is certainly an example
of a p u b l i c a t i o n in w h i c h there is s o m e t h i n g for everybody.
Those interested in pediatric otolaryngology w i l l be pleased
w i t h t h e c l u s t e r o f c h a p t e r s d e a l i n g w i t h t o p i c s s u c h as: " S e p t o -
plasty and Rhinoplasty in the Pediatric Age G r o u p " by Drs. Charles
W. Gross a n d S t e p h e n S. Park, a n d " A n e s t h e s i a for the Pediatric
O t o l a r y n g i c P a t i e n t " by Drs. J. Scott H i l l a n d Peter J. Davis. T h e
provocative socioeconomic p r o b l e m of "Guidelines for Inpatient
Versus O u t p a t i e n t A d e n o t o n s i l l e c t o m y in C h i l d r e n " is presented
i n a v e r y b a l a n c e d w a y b y Dr. M i c h a e l C u n n i n g h a m . Dr. N . W e n -
dall T o d d has chosen the very p r o v o c a t i v e title of " T h e Special
Child's A i r w a y From Nose to Larynx," w h i c h is filled w i t h some
v e r y g o o d w a y s t o stay o u t o f t r o u b l e . Dr. F r a n k l i n L . R i m e l l u p -
dates u s o n " W h a t ' s N e w i n t h e M a n a g e m e n t o f R e s p i r a t o r y P a p i l -
l o m a t o s i s " i n c h i l d r e n , a n d Dr. Y v o n n e S i n i n g e r presents u s w i t h
w h e r e w e n o w stand i n " S c r e e n i n g for H e a r i n g Loss i n Neonates."
T h o s e i n t e r e s t e d i n p l a s t i c s u r g e r y w i l l f i n d a great d e a l o f i n -
f o r m a t i o n p r e s e n t e d i n a n i m a g i n a t i v e w a y b y Dr. S h a n B a k e r i n
"Contemporary Aspects of Nasal Reconstruction."
For the otologists in the g r o u p , Dr. Charles B l u e s t o n e , one of
the p i o n e e r s in t h i s area a n d a m e m b e r of o u r E d i t o r i a l B o a r d , has
written a chapter entitled "Management of the A b n o r m a l l y Patu-
lous Eustachian Tube," w h i c h is an u n u s u a l but vexing problem
for otolaryngologists. Dr. L o m e Parnés has p r o v i d e d u s w i t h the
chapter " I n t r a t y m p a n i c P h a r m a c o t h e r a p y for I n n e r Ear D i s o r d e r s , "
w h i c h is very w e l l w r i t t e n and full of i n f o r m a t i o n about the ad-
v a n c e s m a d e i n t h e t r e a t m e n t o f v a r i o u s d i s o r d e r s o f t h e i n n e r ear.
T h e r e is also a cluster of papers for those interested in h e a d
a n d n e c k surgery. Dr. Jeffrey N . M y e r s tells u s a b o u t the r e m a r k -
able advances m a d e i n h i s chapter e n t i t l e d " T h e Use o f B i o l o g i c a l
Therapy in Cancer of the Head and Neck." We have added an i n -
ternational flavor to this v o l u m e of Advances as Drs. Jean-Louis
Lefebvre a n d D o m i n i q u e Chevalier discuss " S u p r a c r i c o i d Partial

xi
xii Preface

L a r y n g e c t o m y , " (the F r e n c h o p e r a t i o n ) . Dr. H e i n r i c h R u d e r t f r o m


Germany presents his experience w i t h "Laser Surgery in the M a n -
agement of Carcinoma of the Supraglottic L a r y n x and Hypophar-
y n x , " (the G e r m a n o p e r a t i o n ) . Last b u t b y n o m e a n s least, Profes-
sor W i l l i a m W e i o f H o n g K o n g has w r i t t e n a chapter based u p o n
his v o l u m i n o u s experience on "Carcinoma of the Nasopharynx,"
(the Chinese cancer).
Drs. Charles Bluestone, Derald B r a c k m a n n , Charles Krause,
and I all have w o r k e d diligently to organize this v o l u m e together
w i t h M a r y Jo T u t c h k o , o u r e d i t o r i a l assistant. M o s b y , Inc. has been
a t t e n t i v e t o o u r n e e d s , a n d w e are v e r y p r o u d o f V o l u m e 12.
Eugene N. Myers, M.D.
Editor-in-Chief
Contents

Contributors vii
Preface xi

1. Supracricoid Partial Laryngectomy


By fean-Louis Lefebvre and Dominique Chevalier 1
History 1
Anatomical, Pathologic, and Physiologic Background 3
Surgical Techniques 4
SCPL with CHP (Fig 3) 4
SCPL with CHEP (Fig 4) 7
Postoperative Care 9
Summary of M a j o r Technical Key Points 9
Indications 9
SCPL with CHP 9
SCPL with CHEP 10
Results 11
Glottic Cancers 11
Supraglottic Cancers 13
Conclusion 14

2. Intratympanic Pharmacotherapy for Inner Ear Disorders


By Lome S. Parnes 17
Tinnitus 18
Meniere's Disease 18
Current Gentamicin Administration Technique
and Protocol 20
Results 22
Discussion 24
Inflammatory Inner Ear Disorders 24
Intratympanic Corticosteroid Experience 25
Discussion 34

xiii
xiv Contents

3. Guidelines for Inpatient Versus Outpatient


Adenotonsillectomy in Children
By Michael J. Cunningham 41
Procedure Complications 41
Inpatient/Outpatient Adenotonsillectomy Studies 43
Identification of High-Risk Subgroups 50
Ages Younger Than Or Equal to 3 Years 50
Obstructive Sleep Disorder (Obstructive Apnea) 53
Concomitant Systemic Disorders 55
Concomitant A i r w a y Problems 55
Concomitant Bleeding Disorder 56
W h e n the Procedure is Being Done for Acute Peritonsillar
Abscess 56
Clinical intangibles 57
Conclusion 57

4. Laser Surgery in the Management of Carcinoma of the


Supraglottic Larynx and Hypopharynx
By Heinrich H. Budert 61
Anatomical Preliminary Remarks and Conformity of Tumor
Growth 63
Anesthesia 65
Instruments and Laser Systems 65
Resection Techniques 68
Resection of Tumors of the Suprahyoid Epiglottis 68
Resection of Tumors of the Infrahyoid Epiglottis 70
Resection of False Cord Tumors 72
Resection of Tumors of the Aryepiglottic Folds 72
Resection of Tumors of the Posterior W a l l
of the Hypopharynx 72
Resection of Tumors of the Lateral W a l l
of the Hypopharynx 72
Resection of Tumors of the Piriform Sinus Walls 73
Treatment of the Regional Lymphatic Drainage 73
Oncologic Results 74
Functional Results 76
Conclusion 77
Contents xv

5. The Special Child's Airway From Nose to Larynx


By N. Wendell Todd 81
Nomenclatures 83
Patient Assessments 83
History 83
Physical Examination 84
Endoscopy 85
Imaging 86
Polysomnography 87
Differential Diagnosis 88
Therapeutic Interventions 88
Ethics 88
Management 90
Positive Intraluminal A i r w a y Pressure 92
Growth Considerations 92
Interactions of Multiple Obstructions 93
Emergent Calls about the Airways of Special Children 93
Illustrative Patient Vignettes 94
Bad A i r w a y ; Difficult Ethics 94
Challenging Airway, Worsened by Closure of Cleft
Palate 94
Gravitational Glossoptosis 95
Misdiagnosis, Peculiar Constellation, Satisfying Result 96
"Routine" Tonsillectomy and Adenomectomy; Special
M a y Not Be Obvious 96

6. What's New in the Management of Respiratory


Papillomatosis?
By Frank L. Bimell 101
Pathologic Characteristics of RRP 101
Juvenile and Adult Disease 102
Benign and Aggressive Disease 103
Viral Transmission 103
Surgical Management 104
Anesthesia and A i r w a y Management 104
Evaluation and Staging 105
Laser Surgery 105
Tracheotomy 107
Medical Management 107
xvi Contents

Interferon 107
lndol-3-Carbinol 109
Acyclovir 1 10
Isotretinoin 1 11
Methotrexate 1 11
Ribavirin 112
Disease Complications 112
Treatment Complications 113
Summary 1 14

7. Carcinoma of the Nasopharynx


By William Ignace Wei 1 19
Diagnosis 120
CT 120
MRI 120
Treatment 121
Radiotherapy 121
Surgery 122
Cervical Lymph N o d e Metastases 123
Primary Nasopharyngeal Tumor 1 25
Brachytherapy 125
Surgical Resection 125

8. T h e Use of Biological T h e r a p y in Cancer of the H e a d


and Neck
By Jeffrey N. Myers 133
Tumor Evolution A n d Multistep Models of Carcinogenesis 1 34
Gene Therapy For Cancer of The Head A n d Neck 1 35
Background 135
History 136
Methods of Gene Delivery 1 36
Gene Therapy Strategies 140
Immunotherapy for Cancer of the Head and Neck 148
Evidence for the Theory of Immunosurveillance 149
Cellular Cancer Immunotherapy 150
Immunotherapy with IL-2 150
IL-2 Immunotherapy for Cancer of the Head and Neck 151
Other Cytokines Used in Immunotherapy for Cancer
of the Head and Neck 152
Contents xvii

Antigen Presenting Cells in Immunotherapy 153


Summary 154

9. Septoplasty and Rhinoplasty in the Pediatric Age Group


By Stephen S. Park and Charles W. Gross 165
Embryology and Anatomy 165
Pathophysiology 166
Pediatric Considerations 167
Technique 171
Representative Case 175
Conclusion 175

1 0 . Screening for Hearing Loss in Neonates: Where Do We


Stand?
By Yvonne S. Sininger 1 81
History 183
Crib-o-Gram 183
Joint Committee on Infant Hearing and High Risk
Register 183
ABR 186
Federal Activity and NIH-Funded Screening Project 186
N I H Consensus Development Conference 1 87
Principles of Screening 1 89
Target Disorder 1 89
Operating Characteristics 190
OAEs in Infant Screening 192
ABR 195
Combined ABR-OAE Protocols 197
Auditory Neuropathy 197
Personnel and Cost Issues 198
Parental Concerns 198
Current Status of N e w b o r n Screening in the United States 199

1 1 . Management of the Abnormally Patulous Eustachian Tube


By Charles D. Bluestone 205
Epidemiology 206
xviii Contents

Physiology and Pathophysiology of the Eustachian Tube 207


Pressure Regulation ("Ventilatory Function") 208
Protective Function 208
Patulous Eustachian Tube 21 1
Etiology and Pathogenesis 213
Clinical Presentation 214
Diagnostic Tests 215
Tympanometry 215
Manometry 217
Other Tests 21 8
Management 218
Nonsurgical Methods 218
Surgical Methods 220
Catheter Obstruction of the Eustachian Tube 221

12. C o n t e m p o r a r y Aspects of N a s a l Reconstruction


By Shan Baker 235
Historical Approaches 236
Contemporary Approaches 237
Facial Aesthetic Regions 238
Lining Flaps 240
Framework 245
Covering Flaps 247
Melolabial Interpolation Flap 249
Paramedian Forehead Flap 250
Defect Classification 256
Reconstruction of Columella 257
Reconstruction of Lobule 258
Reconstruction of the Ala 258
Reconstruction of the Nasal Dorsum 259
Reconstruction of the Sidewall of the Nose 260
Summary 260

13. Anesthesia for the Pediatric Otolaryngic Patient


By Jimmy Scott Hill and Peter J. Davis 263
General Preoperative Evaluation 264
Preoperative Evaluation 264
Psychological 264
Pharmacology 265
Contents xix

Regarding Fasting 267


Blood Transfusion 267
Surgical Risk 268
History 268
Anesthetic Induction 269
A i r w a y Management 270
Maintenance Anesthesia 271
Special Problems in Preoperative Evaluation of Otolaryngic
Patients 273
Pulmonary 273
Cardiovascular Disorders 282
Hematologic/Oncologic/lmmunologic Disorders 284
Neurologic 292
Miscellaneous Disorders 294
Summary 296
Index 309
CHAPTER 1
Supracricoid Partial
Laryngectomy
Jean-Louis Lefebvre, M.D.
Professor of ENT, Head and Neck Surgery, Deputy Director and Chief,
Head and Neck Department, Centre Oscar Lambret (Northern France
Comprehensive Cancer Center), Lille, France
Dominique Chevalier, M.D.
Professor of ENT, Head and Neck Surgery, Lille University Medical
School; ENT, Head and Neck Surgery Science, Hôpital Claude Huriez
(University Medical Center), Lille, France

S u p r a c r i c o i d p a r t i a l l a r y n g e c t o m i e s (SCPL) are f u n c t i o n a l p r o -
cedures suitable for the treatment of m o d e r a t e l y advanced la-
ryngeal cancers. T h e y p r o v i d e a surgical alternative to the c o n v e n -
tional partial laryngectomies (either horizontal or vertical) a n d the
classic total l a r y n g e c t o m y . A c t u a l l y , there w a s a gap for some bor-
d e r l i n e cases ( f o r e x a m p l e , a t u m o r o f t h e i n f r a h y o i d e p i g l o t t i s
reaching or slightly involving, d o w n w a r d , the anterior commis-
sure; or a t u m o r of an entire v o c a l c o r d o v e r l a p p i n g the anterior
commissure and i n v o l v i n g the anterior part of the contralateral
c o r d ) . I n fact, t h e r e are t w o d i f f e r e n t t y p e s o f S C P L . U s u a l l y , S C P L
w i t h c r i c o h y o i d o e p i g l o t t o p e x y (CHEP) is indicated for the surgi-
cal treatment of glottic cancer, a n d SCPL w i t h c r i c o h y o i d o p e x y
(CHP) is i n d i c a t e d for supraglottic cancer or glottic cancer w i t h su-
praglottic extension. These t e c h n i q u e s p r o v i d e a large resection of
the laryngeal structures. T h e y do n o t n e e d any k i n d of flap for clo-
sure because the laryngeal r e c o n s t r u c t i o n is p e r f o r m e d w i t h the la-
r y n g e a l s t r u c t u r e s left i n p l a c e (Fig 1). I n b o t h p r o c e d u r e s , i t i s nec-
essary t o preserve a t least o n e a r y t e n o i d cartilage, t h e h y o i d b o n e ,
t h e c r i c o i d cartilage a n d , i n t h e case o f CHEP, t h e e p i g l o t t i s t o a l -
l o w speech, s w a l l o w i n g , and decannulation.

HISTORY
T h e p r i n c i p l e s of a s u p r a c r i c o i d l a r y n g e c t o m y w e r e first described
1
i n 1959 b y Majer a n d Rieder i n V i e n n a . Their f i r s t experience was
9
Advances in Otolaryngology-Head and Neck Surgery , vol. 12
«1998, Mosby, Inc.
J.-L. Lefebvre and D. Chevalier

FIGURE 1.
Sketches of supracricoid partial laryngectomies. Left, preoperative sketch;
upper right, cricohyoidopexy; lower right, cricohyoidoepiglottopexy.

based on six patients w i t h glottic or supraglottic laryngeal cancers.


At that time, the procedure was called "cricohyoidopexy," a n d the
m a i n conclusions of their paper focused on the selection of patients
w i t h b u l k y tumors and w i t h o u t subglottic extension.
2
I n 1 9 7 0 , A r s l a n a n d S e r a f i n i p u b l i s h e d f o u r cases o f l a r y n g e a l
cancers treated w i t h a similar technique, b u t the c r i c o i d cartilage
w a s also r e m o v e d . As a result, t h e y r e c o n s t r u c t e d the r e m a i n i n g
3
larynx w i t h a tracheohyoidoepiglottopexy. In 1971, Labayle pub-
lished a technique of near total laryngectomy, keeping in place the
h y o i d b o n e a n d r e m o v i n g o n l y t h e s u p e r i o r p a r t o f t h e c r i c o i d car-
tilage t h r o u g h a horizontal resection. T h e laryngeal reconstruction
was achieved by a cricohyoidopexy.
4
In 1974, Piquet p u b l i s h e d a technique of SCPL w i t h CHER
T h i s w a s t h e first r e p o r t , a n d t h i s a u t h o r r e p o r t e d a series of 23
patients w i t h glottic carcinomas. Piquet stressed that the preserva-
tion of the superior t w o thirds of the epiglottis had i m p r o v e d the
functional result w i t h o u t having jeopardized the local control
Supracricoid Partial Laryngectomy 3

a c h i e v e d i n a l l t h e cases, w h e r e a s t w o p a t i e n t s r e l a p s e d i n t h e
5
neck. In 1976, Piquet redefined b o t h the techniques a n d the i n d i -
cations o f S C P L w i t h C H P a n d C H E P i n a series o f 6 1 p a t i e n t s .
This surgery became very p o p u l a r in France and several reports
confirmed, in terms of oncologic a n d functional results, the reli-
6 - 1 3
ability of S C P L . T h i s surgery has been w r i t t e n about u n d e r v a r i -
ous names, i n c l u d i n g " s u b t o t a l l a r y n g e c t o m i e s , " " r e c o n s t r u c t i v e
laryngectomies," "supracricoid laryngectomies," or "cricos."

ANATOMICAL, PATHOLOGIC, A N D PHYSIOLOGIC BACKGROUND


T h e concept of this surgery is based on three key issues:

1. The cricoid ring must be preserved to calibrate the remaining


larynx a n d to ensure satisfactory breathing.
2. At least o n e a r y t e n o i d m u s t be p r e s e r v e d to p r o d u c e a v i b r a -
t i o n against t h e base o f t h e t o n g u e a n d t o a l l o w satisfactory
phonation.
3. The r e m a i n i n g larynx ( w i t h or w i t h o u t the upper part of the
epiglottis) m u s t b e able t o m o v e u p w a r d a n d f o r w a r d , b e l o w
t h e base of t o n g u e , to a l l o w a satisfactory d e g l u t i t i o n w i t h o u t
aspiration.

T h e identification of the laryngeal structures to be removed is


based on the k n o w l e d g e of the routes of extension of cancer of the
l a r y n x . T u m o r s o f t h e l a r y n g e a l surface o f t h e e p i g l o t t i s m a y ex-
tend superficially in all directions (and possibly to the anterior part
of the glottis). T h e y also m a y e x t e n d d e e p l y i n t o the pre-epiglottic
space by three routes: t h r o u g h the n a t u r a l holes traversing the e p i -
glottic cartilage; t h r o u g h the cartilage w h e n i n v a d e d ; or inferiorly,
just above t h e a n t e r i o r c o m m i s s u r e after d i s i n s e r t i o n o f the i n f e -
rior thyroepiglottic ligament at the level of the petiole. Tumors of
the false v o c a l c o r d s also m a y e x t e n d i n a l l d i r e c t i o n s a n d t o the
v e n t r i c l e o r t h e a r y t e n o i d . T u m o r s o f t h e t r u e v o c a l cords m a y ex-
t e n d superficially t o w a r d the ventricle, the vocal process a n d the
a r y t e n o i d itself, the subglottic area, a n d the anterior c o m m i s s u r e .
T h e y m a y e x t e n d d e e p l y to the paraglottic space w h e r e the exten-
sion is contained, as long as the conus elasticus is preserved. T u -
mors of the anterior commissure quickly involve the thyroid carti-
lage (there i s n o p e r i c h o n d r i u m a t t h i s level) a n d m a y e x t e n d
through the cricothyroid membrane.
The evaluation of the t u m o r extension requires thorough study.
A classic l a r y n g o s c o p y is necessary to get a p a n o r a m i c v i e w of t h e
larynx morphology and mobility, a panendoscopy w i t h rigid
4 J.-L. Lefebvre and D. Chevalier

30-degree a n d 70-degree telescope e x p l o r a t i o n , a n d appropriate i m -


aging (CT scan a n d / o r M R I ) . A t t e n t i o n m u s t be p a i d to the patient's
p e r f o r m a n c e status, especially to his p u l m o n a r y f u n c t i o n , inas-
m u c h as some aspiration may occur during the postoperative
course w h e n n o r m a l s w a l l o w i n g r e s t o r a t i o n i s a t t e m p t e d . A s far
as e v a l u a t i o n of local extension is concerned, an i m p o r t a n t differ-
entiation must be made between vocal cord i m m o b i l i t y due either
to paraglottic space i n v a s i o n or c r i c o a r y t e n o i d j o i n t i n v o l v e m e n t
(two different T3), a n d b e t w e e n t h y r o i d cartilage i n v a s i o n that can
be detected clinically or only on imaging (two different T4).

SURGICAL TECHNIQUES
S u p r a c r i c o i d l a r y n g e c t o m i e s w i t h C H P o r C H E P are b a s e d o n t h e
same p r i n c i p l e s , b u t t h e p r o c e d u r e s are q u i t e d i f f e r e n t (Fig 2 ) a n d
m u s t be described separately.

SCPL WITH CHP (FIG 3)


1. Preparation. T h e p r o c e d u r e is c o n d u c t e d u n d e r general anes-
thesia. T h e patient is i n t u b a t e d , a nasogastric feeding tube is
inserted, a n d a shoulder roll is placed.
2. Exposure of the larynx. T h e skin is incised using a " U - t y p e "
incision along the anterior border of the sternocleidomastoid
muscles. A subplatysmal s k i n flap is elevated superiorly above

FIGURE 2.
Larynx resection in supracricoid partial laryngectomies. Left, cricohyoi-
doepiglottopexy. Right, cricohyoidopexy.
Supracricoid Partial Laryngectomy 5

FIGURE 3.
Surgical specimen of SCPL with CHP. Tumor of the infrahyoid epiglottis
involving the left ventricle and the anterior commissure mucosa with se-
vere dysplasia on the right true vocal cord.

the level of the h y o i d bone on the m i d l i n e and at the level of


the m a s t o i d process laterally. At that t i m e , according to the p r i -
m a r y site a n d t h e size o f t h e largest p a l p a b l e l y m p h n o d e , i f
any, a bilateral n e c k dissection ( m o d i f i e d or not) is p e r f o r m e d .
T h e s t e r n o h y o i d , s t e r n o t h y r o i d , a n d t h y r o h y o i d m u s c l e s are
transected. The larynx is rotated using a hook, and the constric-
tor m u s c l e s are t r a n s e c t e d a l o n g t h e p o s t e r i o r b o r d e r o f t h e t h y -
r o i d cartilage l a m i n a b e g i n n i n g at the superior c o r n u . T h e ex-
ternal t h y r o i d p e r i c h o n d r i u m is elevated a n d the p i r i f o r m si-
nus is released. T h e superior laryngeal neurovascular pedicle
i s i d e n t i f i e d . T h e a r t e r y a n d t h e v e i n are l i g a t e d , s p a r i n g t h e
superior laryngeal nerve. The procedure is similar on both
sides of the larynx.
f . - L . Lefebvre and D. Chevalier

Inferiorly, the resection is prepared. The cricothyroid muscles


are c a r e f u l l y t r a n s e c t e d a n t e r i o r l y t o e x p o s e t h e c r i c o t h y r o i d m e m -
brane. T h e i n f e r i o r c o r n u is transected at its base if t h e a r y t e n o i d
cartilage is preserved to a v o i d recurrent laryngeal nerve injury. T h e
c r i c o t h y r o i d j o i n t s c a n also be d i s a r t i c u l a t e d c a r e f u l l y for the same
reason. T h e n the isthmus of the t h y r o i d gland is transected and l i -
gated. A l o w tracheotomy is performed (fourth or fifth tracheal
ring), because at closure the trachea w i l l m o v e up w i t h the cricoid
cartilage.
Superiorly, the h y o i d bone is exposed. The periosteum of the
h y o i d b o n e i s i n c i s e d a n t e r i o r l y a n d t h e fat o f t h e p r e - e p i g l o t t i c
space is dissected i n f e r i o r l y f r o m the posterior surface of the h y -
oid bone. This is carefully performed to avoid opening the
p r e - e p i g l o t t i c s p a c e , p a r t i c u l a r l y i n case o f s u p r a g l o t t i c c a n c e r .

3. Excision. Once the exposure is completed, the larynx is opened


f r o m above, w h i c h allows good t u m o r exposure. The h y o i d
bone is elevated a n d the t h y r o i d cartilage is p u l l e d inferiorly
w i t h the pre-epiglottic space. T h e l a r y n x is entered by a clean
c u t u s i n g a b l a d e or scissors, a n d v a l l e c u l a e are t r a n s e c t e d . T h e
epiglottis is grasped w i t h a c l a m p to expose the supraglottis
and the tumor. The resection is performed under direct vision
starting on the site o p p o s i t e the t u m o r . A cut is m a d e anterior
to the arytenoid beginning at the level of the aryepiglottic fold
a n d is c o n t i n u e d inferiorly, preserving the vocal process. Dur-
ing that time, the p i r i f o r m sinus is spared a n d reflected poste-
riorly. The cricothyroid membrane is incised at the superior
b o r d e r o f t h e c r i c o i d cartilage. T h e n t h e scissors are p l a c e d
horizontally and the superior incision (aryepiglottic fold, vo-
cal cord) joins the inferior i n c i s i o n (cricothyroid membrane).
At that time, it is i m p o r t a n t to avoid i n j u r y of the lateral crico-
t h y r o i d m u s c l e , because i t w i l l assist t h e a n t e r i o r m o t i o n o f t h e
a r y t e n o i d . I f b o t h a r y t e n o i d s are s p a r e d , t h e r e s e c t i o n i s c o n -
ducted w i t h the same technique. If one arytenoid is resected
on the side of the tumor, mucosa is cut over the arytenoid con-
serving the posterior mucosa, then is continued vertically in
the posterior subglottis through the interarytenoid muscle. A n -
teriorly, this incision joins the incision in the cricothyroid
membrane.
4. Closure. A f t e r c a r e f u l h e m o s t a s i s , t h e p i r i f o r m sinuses are
checked to ensure that there have been no accidental perfora-
tions. If necessary, the r e m a i n i n g a r y t e n o i d m u c o s a is s e w n
over the d e n u d e d c r i c o i d cartilage (3-0 V i c r y l ) o n t h e s i d e o f
Supracricoid Partial Laryngectomy 7

the arytenoid resection so that the b u l k of the m u c o s a forms a


p s e u d o a r y t e n o i d . T h e l a r y n x i s c l o s e d u s i n g t h r e e stitches (2-0
Vicryl), one on the m i d l i n e a n d t w o lateral. These stitches en-
circle t h e c r i c o i d , cross t h e base o f t h e t o n g u e , a n d e n c i r c l e t h e
h y o i d bone. A f t e r the k n o t s are t i e d , the c r i c o i d comes i n t o c o n -
tact w i t h t h e base o f t h e t o n g u e , a n d t h e t r a c h e o t o m y site
s h o u l d c o m e t o t h e rest o f t h e s k i n i n c i s i o n . T h e a n t e r i o r bor-
ders o f the h y o i d b o n e a n d c r i c o i d cartilage m u s t b e c a r e f u l l y
aligned.

SCPL WITH CHEP (FIG 4)


T h i s p r o c e d u r e i s d e s i g n e d f o r t h e s u r g i c a l t r e a t m e n t o f g l o t t i c car-
cinoma. T h e surgical technique differs f r o m SCPL w i t h C H P in that
the epiglottis is preserved. O t h e r w i s e the preparation is similar.

1. Exposure of the larynx. T h e s k i n is incised using a " U - t y p e "


incision along the anterior border of the sternocleidomastoid
muscles. A subplatysmal s k i n flap is elevated superiorly above
the level of the h y o i d bone on the m i d l i n e . At that time, an
ipsilateral functional neck dissection is performed if indicated.
T h e n t h e s t e r n o h y o i d m u s c l e s are d i v i d e d i n t h e m i d l i n e a n d

FIGURE 4.
Surgical specimen of SCPL with CHEP. Tumor of the right true vocal cord
involving the anterior commissure (plus thyroid cartilage), the right ven-
tricle, and the right arytenoid (resected).
f.-L. Lefebvre and D. Chevalier

r e t r a c t e d laterally. T h e s t e r n o t h y r o i d m u s c l e s are t r a n s e c t e d
a n d the prelaryngeal fibrofatty tissue is dissected along w i t h
the Delphian l y m p h node. The larynx is rotated using a hook,
a n d t h e c o n s t r i c t o r m u s c l e s are t r a n s e c t e d a l o n g t h e p o s t e r i o r
border of the t h y r o i d cartilage l a m i n a b e g i n n i n g at the supe-
rior cornu. The external thyroid p e r i c h o n d r i u m is elevated, and
the p i r i f o r m sinus is released. The superior laryngeal neuro-
v a s c u l a r p e d i c l e i s i d e n t i f i e d . T h e artery a n d t h e v e i n are l i -
gated, sparing the superior laryngeal nerve. The procedure is
s i m i l a r on b o t h sides of the l a r y n x . T h e surgeon's a t t e n t i o n is
t h e n d i r e c t e d i n f e r i o r l y w h e r e the c r i c o t h y r o i d m u s c l e s are
carefully transected anteriorly to expose the cricothyroid m e m -
brane. T h e subglottic mucosa overlying the cricoid cartilage is
elevated on the side of the glottic t u m o r using a s m a l l elevator,
to achieve w i d e r resection on the tumor-bearing side. T h e
i n f e r i o r c o r n u is t r a n s e c t e d at its base on t h e side o p p o s i t e to
the t u m o r to avoid injuring the recurrent laryngeal nerve dur-
i n g the excision of the t h y r o i d cartilage. T h e inferior c o r n u on
the side of the t u m o r is disarticulated to a l l o w the paraglottic
space to be c o m p l e t e l y r e m o v e d . T h e n the i s t h m u s of the
t h y r o i d gland is transected and ligated. A l o w tracheotomy is
performed.
2. Excision. Once the exposure is completed, the larynx is
opened. The t h y r o h y o i d membrane is incised and the epiglot-
tis is t r a n s e c t e d at its base by a c l e a n c u t u s i n g a b l a d e at the
base of the petiole. T h i s step is i m p o r t a n t , because m a i n t a i n -
i n g the integrity of the epiglottis guarantees an o p e n i n g for the
reconstructed larynx. T h e larynx is opened f r o m above just su-
p e r i o r t o the false v o c a l cords, t h u s a l l o w i n g g o o d t u m o r e x p o -
sure. On the side opposite the tumor, a cut is m a d e anterior to
the arytenoid, thus preserving the vocal process, a n d is con-
t i n u e d i n f e r i o r l y t o the s u p e r i o r b o r d e r o f the c r i c o i d . T h e lat-
eral c r i c o a r y t e n o i d m u s c l e is spared on this side because it w i l l
assist t h e a n t e r i o r m o t i o n o f t h e r e m a i n i n g a r y t e n o i d . O n the
s i d e o f t h e t u m o r , t h e e x c i s i o n i s w i d e r ; cuts are m a d e o v e r t h e
arytenoid, conserving the posterior mucosa, then continued
vertically in the posterior subglottis through the interarytenoid
muscle. Anteriorly, this incision joins the incision in the cri-
cothyroid membrane by making a right-angle turn from medial
to lateral. T h e excision of the t u m o r w i t h the t h y r o i d cartilage
i s p e r f o r m e d a n d removes t h e entire paraglottic space w i t h the
specimen.
3. C l o s u r e . A f t e r c a r e f u l hemostasis, the p i r i f o r m sinuses are
checked. A probe is inserted in the ventricle to verify that it
Supracricoid Partial Laryngectomy 9

has been c o m p l e t e l y r e m o v e d , as a r e m a i n i n g p o r t i o n of v e n -
tricle m u c o s a s h o u l d d e v e l o p i n t o a cyst. If necessary, t h e re-
m a i n i n g arytenoid mucosa is s e w n over the d e n u d e d cricoid
c a r t i l a g e (3-0 V i c r y l ) o n t h e s i d e o f t h e a r y t e n o i d r e s e c t i o n s o
t h a t t h e b u l k o f t h e m u c o s a f o r m s a p s e u d o a r y t e n o i d . T h e lar-
y n x i s c l o s e d u s i n g t h r e e s t i t c h e s (2-0 V i c r y l ) , o n e m i d l i n e a n d
t w o lateral. These stitches e n c i r c l e t h e c r i c o i d , cross t h e e p i -
glottis a n d the base o f the t o n g u e , a n d t h e n encircle the h y o i d
b o n e . A f t e r t h e k n o t s are t i e d , t h e c r i c o i d c o m e s i n t o c o n t a c t
w i t h t h e b a s e o f t h e t o n g u e a n d t h e h y o i d b o n e . A s i s t h e case
after S C P L w i t h CHP, t h e t r a c h e o t o m y site s h o u l d c o m e t o rest
in the skin incision, and the anterior borders of the h y o i d bone
a n d cricoid cartilage m u s t be carefully aligned.

POSTOPERATIVE CARE
Intravenous antibiotic treatment is a d m i n i s t e r e d for 10 days. A na-
sogastric t u b e r e m a i n s i n place. T h e t r a c h e o t o m y tube i s p l u g g e d
as soon as can be tolerated by the patient, usually a r o u n d the eighth
day, a n d t h e n c a n be r e m o v e d . O r a l f e e d i n g begins as s o o n as t h e
p a t i e n t c a n s w a l l o w saliva, u s u a l l y a r o u n d t h e t e n t h day. D u r i n g
the p o s t o p e r a t i v e course, the p a t i e n t is asked to p h o n a t e early, a n d
the speech therapist m u s t be i n v o l v e d in the rehabilitation of the
patient. It is important to motivate the patient so that the postop-
erative course is quicker and smoother.

SUMMARY OF MAJOR TECHNICAL KEY POINTS


SCPL w i t h CHP: The dissection of the inner p e r i c h o n d r i u m at the
posterior face o f the h y o i d b o n e m u s t b e c a r e f u l l y p e r f o r m e d t o e n -
sure a c o m p l e t e r e m o v a l of the p r e - e p i g l o t t i c space.
SCPL w i t h CHEP: T h e opening of the larynx m u s t be performed
exactly at the level of the petiole of the epiglottis. The subglottic
mucosa overlying the cricoid cartilage is elevated w i t h the inner
p e r i c h o n d r i u m on the side of the t u m o r a n d is t h e n resected.
S C P L w i t h e i t h e r C H P o r C H E P : T w o p o i n t s are o f i m p o r t a n c e :
one is to preserve the recurrent laryngeal nerve w i t h the remain-
ing arytenoid(s). T h e second is, at t i m e of closure, the p e x y m u s t
i m p a c t h y o i d bone a n d c r i c o i d cartilage at the same level.

INDICATIONS
SCPL WITH CHP
Supraglottic carcinoma: SCPL w i t h CHP is indicated w h e n supra-
glottic c a r c i n o m a s are n o l o n g e r s u i t a b l e for h o r i z o n t a l s u p r a g l o t -
tic l a r y n g e c t o m y a n d w h e n a total l a r y n g e c t o m y seems too ex-
tensive.
J.-L. Lefebvre and D. Chevalier

T h e i n d i c a t i o n s are:

• Supraglottic tumors extending to the ventricle and/or the poste-


r i o r t h i r d o f t h e false v o c a l c o r d
• Supraglottic t u m o r s extending to the glottis, i n c l u d i n g the ante-
rior commissure w i t h or w i t h o u t i m p a i r e d m o b i l i t y of the true
vocal cord
• S e l e c t e d cases o f i n f r a h y o i d e p i g l o t t i c c a r c i n o m a s p r e s e n t i n g
w i t h pre-epiglottic space i n v a s i o n
• S e l e c t e d cases o f s u p r a g l o t t i c t u m o r p r e s e n t i n g w i t h l i m i t e d t h y -
r o i d cartilage i n v a s i o n

7
Those t w o particular indications were presented by Chevalier
and Laccourreye" and need a precise preoperative imaging
evaluation.
G l o t t i c c a r c i n o m a s : A n y case w i t h s u p r a g l o t t i c e x t e n s i o n .

• T u m o r of the anterior c o m m i s s u r e w i t h a deep i n v a s i o n at the


level of the petiole of the epiglottis
• Tumor of the true vocal cord w i t h invasion of the ventricle, the
false v o c a l c o r d , or the epiglottis

W h a t e v e r t h e p r i m a r y site, c o n t r a i n d i c a t i o n s are:

• A r y t e n o i d cartilage fixation due to c r i c o t h y r o i d joint i n v a s i o n


• M a s s i v e i n v a s i o n of the pre-epiglottic space
• Massive invasion of the t h y r o i d cartilage and/or extralaryngeal
invasion
• Subglottic extension more than 7 mm anteriorly or more than
5 m m p o s t e r i o r l y , a s t h e s e cases t e n d t o i n v o l v e t h e c r i c o i d
cartilage
• Invasion of the s u p r a h y o i d epiglottis or of the vallecula
• Preoperative respiratory function impairment

SCPL WITH CHEP


This surgery is o n l y indicated for glottic carcinomas, particularly
w h e n there is a h i g h risk of deep invasion.
I n d i c a t i o n s are:

• Tumor of the anterior t w o thirds of the true vocal cord extend-


ing to the anterior commissure and/or w i t h limited extension to
the floor of the ventricle
Supracricoid Partial Laryngectomy 11

• T u m o r i n v o l v i n g both true vocal cords


• T l o r T 2 t u m o r s w i t h a d j a c e n t areas o f d y s p l a s i a o r i n s i t u car-
cinoma
• T u m o r of the entire true vocal cord w i t h l i m i t e d m o b i l i t y (T3)

C o n t r a i n d i c a t i o n s are:

• A r y t e n o i d cartilage fixation
• Anterior commissure t u m o r w i t h deep invasion
• Subglottic extension more than 7 mm anteriorly and 5 mm pos-
teriorly, as these t e n d to i n v o l v e the c r i c o i d cartilage
• Preoperative respiratory function i m p a i r m e n t

RESULTS
T h e m e d i c a l charts a n d operative files o f 318 patients w h o h a d u n -
dergone SCPL w i t h C H P o r C H E P b e t w e e n 1972 a n d 1995 w e r e ret-
r o s p e c t i v e l y r e v i e w e d . T h e p r i m a r y site w a s the glottis i n 238 a n d
the supraglottic larynx in 80 patients.

GLOTTIC CANCERS
P o p u l a t i o n : In t h i s series, 207 patients u n d e r w e n t a C H E P a n d 31
p a t i e n t s a C H P . T h e m e a n age w a s 5 6 y e a r s ( r a n g e : 37—77). T h e r e
w e r e 2 3 0 m a l e s a n d e i g h t f e m a l e s . D e t a i l s o n t u m o r e x t e n s i o n are
presented in Table 1.
Postoperative courses: O n e patient d i e d of a cervical hemor-
rhage d u r i n g the postoperative p e r i o d (CHEP). For the other
patients, the nasogastric tubes w e r e r e m o v e d , on average, on day
15 (range: 9-38) for the CHEPs a n d day 19 (range: 1 1 - 4 0 ) for the
CHPs. T h e t r a c h e o s t o m y tubes w e r e left in place, on average, 19
days (range: 8-38) for the CHEPs a n d 27 days (range: 2 0 - 9 0 ) for
the CHPs.
Disease c o n t r o l a n d s u r v i v a l : I n the C H E P g r o u p , local recur-
rences o c c u r r e d in 10 patients (4.8%). Surgical salvage w a s
attempted in seven patients a n d was successful in three. Cervical
recurrences occurred in 14 patients (6.7%) a n d were successfully
managed by neck dissection followed by radiotherapy in 11 of 14
patients. The most frequent type of failure was metachronous can-
cers, w h i c h o c c u r r e d i n 2 5 p a t i e n t s . T h e o v e r a l l 5-year s u r v i v a l rate
was 7 6 . 8 % . Causes o f d e a t h w e r e local recurrences i n seven pa-
tients, cervical metastasis in three patients, metachronous cancer
in 17 patients, a n d i n t e r c u r r e n t disease in 18 patients. F o u r patients
w e r e lost to f o l l o w - u p . H e n c e the adjusted s u r v i v a l rate w a s as h i g h
as 8 5 . 4 % .
J.-L. Lefebvre and D. Chevalier

TABLE 1.
Clinical Data of Patients W i t h Glottic Carcinoma

CHEP CHP
n = 207 n = 31
Site of o r i g i n
True vocal cord 193 23
Anterior commissure 13 8
Posterior commissure 1 —
T-stage
Tla 2 0
Tib 25 1
T2 164 29
T3 16 1
N-stage
N0 204 30
N1 30 1
Specific site involved
Anterior commissure 128 18
False vocal cord 2 14
Floor of the ventricle 98 7
Petiole of the epiglottis 2 2
Anterior aspect of arytenoid 102 10
Lateral subglottis 30 1
True vocal cord motion
Normal 82 23
Impaired 85 7
Fixed 15 1
Abbreviations: CHEP, cricohyoidoepiglottopexy; CHP,
c:rk:ohyoidopexy.

In the CHP group, a local recurrence occurred in one patient


(3.2%) a n d c o u l d n o t b e s a l v a g e d . C e r v i c a l r e c u r r e n c e s o c c u r r e d
i n t w o p a t i e n t s (6.4%); o n e i n s t a n c e w a s s u c c e s s f u l l y m a n a g e d
by neck dissection followed by radiotherapy. Metachronous can-
cers o c c u r r e d i n f i v e p a t i e n t s a n d w e r e t h e c a u s e s o f d e a t h i n a l l
cases.
F u n c t i o n a l f a i l u r e s : In t h e C H E P g r o u p , 17 p a t i e n t s h a d a ste-
n o s i s d e v e l o p . T e n cases w e r e d e f i n i t i v e l y c o n t r o l l e d b y C 0 l a s e r
2

and seven required a permanent tracheotomy. In the CHP group,


Supracricoid Partial Laryngectomy 13

t w o patients had persistent aspiration and required closure of the


cricoid cartilage w i t h a shunt a n d permanent tracheostomy. There
w e r e n i n e f u n c t i o n a l f a i l u r e s i n a l l (3.7 % ) .

SUPRAGLOTTIC CANCERS
Population: A l l the patients u n d e r w e n t a SCPL w i t h C H P T h e
m e a n age w a s 5 3 y e a r s ( r a n g e : 29—68). T h e r e w e r e 7 5 m a l e s a n d
f i v e females. D e t a i l s o f t u m o r e x t e n s i o n are p r e s e n t e d i n Table 2 .
Postoperative courses: No patient d i e d d u r i n g the postopera-
tive p e r i o d . T h e nasogastric tubes w e r e r e m o v e d , o n average, o n
day 25 (range: 6 - 8 0 ) . In 56 patients, the t r a c h e o s t o m y t u b e w a s re-

TABLE 2.
Clinical Data of Patients W i t h
Supraglottic Carcinoma

CHP
n = 80
Site of o r i g i n
False v o c a l c o r d 31
Infrahyoid epiglottis 23
Ventricle 16
Petiole of the epiglottis 10
T-stage
Tl 2
T2 52
T3 22
T4 4
N-stage
N0 67
N1 12
N2a 1
Specific site i n v o l v e d
True vocal cord 25
A r y t e n o i d cartilage 28
True vocal cord m o t i o n
Normal 66
Impaired 12
Fixed 2

Abbreviation: CHP, cricohyoidopexy.


14 J.-L. Lefebvre and D. Chevalier

m o v e d before the 4 0 t h day ( 7 0 % ) , whereas 16 patients were de-


c a n n u l a t e d later o n .
Disease c o n t r o l a n d s u r v i v a l : L o c a l recurrences o c c u r r e d i n
three patients ( 3 . 7 % ) a n d w e r e successfully m a n a g e d b y salvage
s u r g e r y i n t w o cases. C e r v i c a l r e c u r r e n c e s a l s o o c c u r r e d i n t h r e e
p a t i e n t s ( 3 . 7 % ) . O n e case w a s s u c c e s s f u l l y m a n a g e d b y r a d i o -
t h e r a p y ; c h e m o t h e r a p y w a s u s e d i n o n e case. D i s t a n t metastases
o c c u r r e d in three patients (liver, lung); n o n e c o u l d be cured. A g a i n
the m o s t frequent t y p e o f failure w a s m e t a c h r o n o u s cancer, w h i c h
o c c u r r e d in 16 patients a n d w a s the cause of death in six.
Functional failures: Six patients required closure of the cricoid
cartilage w i t h a shunt. T w o u n d e r w e n t a total laryngectomy w i t h -
out s h u n t because of persistent aspirations. In total, f u n c t i o n a l fail-
ures o c c u r r e d in 8 patients ( 1 0 % ) .

CONCLUSION
The rationale supporting this n e w surgical approach, w h e n it was
d i s c u s s e d i n t h e e a r l y 70s w a s , o n o n e h a n d , t h e g a p b e t w e e n c o n -
v e n t i o n a l h o r i z o n t a l a n d total laryngectomies a n d , on the other, the
r i s k o f l o c a l recurrences after s o m e v e r t i c a l l a r y n g e c t o m i e s i n the
case o f p a r a g l o t t i c s p a c e i n v a s i o n . T o d a t e , t h e v a r i o u s F r e n c h e x -
periences p r o v i d e c o n v e r g i n g data. Local c o n t r o l w a s achieved i n
a b o u t 9 5 % o f t h e c a s e s ; f u n c t i o n a l f a i l u r e s o c c u r r e d i n less t h a n
1 0 % , w h e r e a s 5-year s u r v i v a l r a n g e d f r o m 8 0 % after C H P t o 8 5 %
after CHEP.
T h i s surgery appears to be suitable for patients free of notable
p u l m o n a r y d y s f u n c t i o n , w h o h a v e m o d e r a t e l y a d v a n c e d diseases
for w h i c h other partial procedures c o u l d be insufficient. In this re-
spect, SCPL a l l o w s the surgeon to a v o i d h a v i n g to p e r f o r m a total
laryngectomy, w h i l e p r o v i d i n g satisfactory surgical margins. T h i s
surgery m u s t be considered as one of the tools we have at our dis-
posal for n o n m u t i l a t i n g m a n a g e m e n t of laryngeal cancers a n d ,
therefore, for l a r y n x f u n c t i o n preservation. Nevertheless, it m u s t
be underscored that this surgery requires t h o r o u g h evaluation for
a p p r o p r i a t e selection of patients regarding t u m o r e x t e n s i o n , per-
f o r m a n c e status, a n d m o t i v a t i o n . Finally, an early re-education dur-
ing the postoperative p e r i o d is, in a d d i t i o n to the attention p a i d to
major technical key points during resection and pexy, the w a y to
i m p r o v e t h e f u n c t i o n a l r e s u l t s a n d t o r e d u c e t h e p o s t o p e r a t i v e stay.

REFERENCES
1. Majer E, Rieder W: Technique de laryngectomie permettant de con-
server la perméabilité respiratoire. Ann Otolaryngol 7 6 : 6 7 7 - 6 8 1 , 1 9 5 9 .
Supracricoid Partial Laryngectomy 15

2. Arslan M, Serafini I: La laryngectomie totale avec rétablissement de


la phonation et de la respiration naturelles. Premiers résultats (4 cas).
Ann Otolaryngol 8 7 : 5 0 9 - 5 1 8 , 1970.
3. Labayle J, Bismuth R: La laryngectomie totale avec reconstruction.
Ann Otolaryngol 8 8 : 2 1 9 - 2 2 8 , 1 9 7 1 .
4. Piquet JJ, Desaulty A, Decroix G: La crico-hyoido-epiglotto-pexie.
Technique opératoire et résultats fonctionnels. Ann Otolaryngol
9 1 : 6 8 1 - 6 8 6 , 1974.
5. Piquet JJ: Functional laryngectomy (cricohyoidopexy). Clin Otolaryn-
gol 1:7-16, 1 9 7 6 .
6. Guerrier B, Lallemant JG, Balmigere G, et al: Notre experience de la
chirurgie reconstructive dans les cancers glottiques. Ann Otolaryngol
1 0 4 : 1 7 5 - 1 7 9 , 1987.
7. Chevalier D, Thill C, Darras JA, et al: Laryngectomie sub-totale fonc-
tionnelle avec crico-hyoido-pexie dans le traitement des tumeurs éten-
dues du larynx. Ann Otolaryngol 1 0 8 : 3 7 8 - 3 8 1 , 1 9 9 1 .
8. Laccourreye O, Brasnu D, Merite-Drancy A, et al: Cricohyoidopexy in
selected infrahyoid epiglottic carcinomas presenting with pathologi-
cal preepiglottic space invasion. Arch Otolaryngol 1 1 9 : 8 8 1 - 8 8 6 , 1 9 9 3 .
9. Laccourreye H, Laccourreye O, Weinstein G, et al: Supracricoid lar-
yngectomy with cricohyoidoepiglottopexy: A partial procedure for
glottic carcinoma. Ann Otol Rhinol Laryngol 9 9 : 4 2 1 - 4 2 6 , 1990.
10. Piquet JJ, Chevalier D: Subtotal laryngectomy with crico-hyoido-
epiglotto-pexie for the treatment of extended glottic carcinomas. Am J
Surg 1 6 : 3 5 7 - 3 6 1 , 1 9 9 1 .
1 1 . Chevalier D, Piquet JJ: Subtotal laryngectomy with cricohyoidopexy
for supraglottic carcinoma: Review of 61 cases. Am J Surg 1 6 8 : 4 7 2 -
473, 1994.
12. Maurice N, Crampette L, Mondain M, et al: Laryngectomie sub-totale
reconstructive avec cricohyoidopexie. Resultats carcinologiques et
suites fonctionnelles précoces A propos de 43 cas. Ann Otolaryngol
1 1 1 : 4 3 5 - 4 4 2 , 1994.
13. Naudo P, Laccourreye O, Weinstein G, Hans S, et al: Functional out-
come and prognosis factors after supracricoid partial laryngectomy
with cricohyoidopexy. Ann Otol Rhinol Laryngol 1 0 6 : 2 9 1 - 2 9 6 , 1997.
CHAPTER 2
Intratympanic
Pharmacotherapy for Inner
Ear Disorders
L o m e S. Parries, M.D., F.R.C.S.C.
Professor, Department of Otolaryngology, The University of Western
Ontario; Associate Chair/Chief, London Health Sciences Centre, London,
Ontario, Canada

T o p i c a l i n s t i l l a t i o n o f i n t r a t y m p a n i c (IT) m e d i c a t i o n s t o treat
i n n e r ear d i s o r d e r s o f f e r s d i s t i n c t a d v a n t a g e s o v e r t h e m o r e
c o n v e n t i o n a l m e t h o d s of systemic p h a r m a c o t h e r a p y or surgery. As
c o m p a r e d w i t h systemic m e d i c a t i o n s , it offers a m o r e direct ap-
p r o a c h t o t h e i n n e r ear w h i l e a v o i d i n g s y s t e m i c d o s i n g a n d its i n -
herent complications. The technique is simpler and m u c h more
c o s t e f f e c t i v e t h a n s u r g e r y , a n d a r g u a b l y m u c h safer. B l a k l e y
recently published an excellent comprehensive review of the
1
subject.
To date, this t e c h n i q u e has been used for three m a i n types of
i n n e r ear d i s o r d e r s : t i n n i t u s , w h i c h has r e c e i v e d v e r y l i t t l e a t t e n -
t i o n i n the literature; M e n i e r e ' s disease, w h i c h has received the
m o s t a t t e n t i o n ; a n d i n f l a m m a t o r y i n n e r ear d i s o r d e r s , c u r r e n t l y t h e
most topical of the three.
T h r e e g e n e r a l classes of d r u g s are u s e d for IT i n j e c t i o n . It
s h o u l d be noted that none of these drugs was specifically devel-
o p e d n o r m a r k e t e d f o r d i r e c t t r a n s t y m p a n i c t r e a t m e n t o f i n n e r ear
d i s o r d e r s . O n e i s the a m i n o g l y c o s i d e class o f a n t i b i o t i c s , w h i c h has
been u s e d extensively for the treatment of M e n i e r e ' s disease, b o t h
transtympanically and systemically. Here, what is normally an u n -
t o w a r d side effect of t h e d r u g , its o t o t o x i c i t y , is c h a n g e d i n t o a
t h e r a p e u t i c c l i n i c a l a p p l i c a t i o n . T h e s e c o n d class o f d r u g s i s l o c a l
anesthetics, w h i c h have also been used b o t h systemically a n d trans-
t y m p a n i c a l l y t o treat t i n n i t u s . F i n a l l y , t h e class that has r e c e i v e d
the most attention recently is the corticosteroids. To date their pre-
Advances in Otolaryngology-Head and Neck Surgery'", vol. 12
«1998, Mosby, Inc. 1'
18 L.S. Parnes

d o m i n a n t use has been systemic, for the management of various


i n f l a m m a t o r y i n n e r ear d i s o r d e r s . H o w e v e r , s o m e r e c e n t r e p o r t s
have described the use of t r a n s t y m p a n i c corticosteroids for the
t r e a t m e n t o f M e n i e r e ' s disease a n d t i n n i t u s .

TINNITUS
A l t h o u g h m u c h has been w r i t t e n o n the i n t r a v e n o u s a d m i n i s t r a -
t i o n of lignocaine a n d lidocaine for the treatment of t i n n i t u s , most
c i t a t i o n s a d d r e s s i n g its I T a p p l i c a t i o n appear i n t h e Japanese lit-
erature. There is no d o u b t i n g the efficacy of the intravenous route,
2
w i t h marked tinnitus suppression in most individuals. H o w -
ever, t h e t r e a t m e n t poses a great r i s k to t h e c a r d i o v a s c u l a r a n d c e n -
tral neurologic systems a n d as such, m u s t be performed in a
h o s p i t a l - t y p e setting w i t h close m o n i t o r i n g . F u r t h e r m o r e the effect
is s h o r t - l i v e d . For these reasons, it has n o t b e e n a c l i n i c a l l y u s e f u l
modality.
I n t r a t y m p a n i c a d m i n i s t r a t i o n w o u l d s e e m t o b e a n a t u r a l off-
shoot of this technique, w i t h the advantage of avoiding the trouble-
some systemic side effects. H o w e v e r , it s t i l l does n o t a v o i d the
p r o b l e m o f the l i m i t e d d u r a t i o n o f efficacy. F u r t h e r m o r e , the ves-
t i b u l a r side effect o f severe a n d p r o l o n g e d vertigo w i t h nausea a n d
v o m i t i n g renders the technique completely impractical.
3
Sakata a n d c o l l e a g u e s h a v e b y far t h e w o r l d ' s largest e x p e r i -
ence u s i n g IT corticosteroids to treat t i n n i t u s . T h e i r i n i t i a l report
of t h e b e n e f i t s of d e x a m e t h a s o n e a p p e a r e d s o m e 15 years ago b u t
4
has never b e e n substantiated in a c o n t r o l l e d study. Coles et a l .
f o u n d l i t t l e if a n y benefit in a s m a l l scale t r i a l of six p a t i e n t s . Sakata
et a l / recently reported their experience using IT dexamethasone
t o t r e a t s o - c a l l e d c o c h l e a r t i n n i t u s i n 1,466 ears o f 1,214 p a t i e n t s
d u r i n g a 2-year p e r i o d . A s s u m i n g , therefore, that t h e y h a v e treated
several t h o u s a n d patients over the years seems reasonable. T h e y
c l a i m to have an overall efficacy rate of 7 2 % , w i t h several differ-
e n t v a r i a b l e s a f f e c t i n g o u t c o m e s . T h e s e i n c l u d e t h e age o f t h e p a -
tient, t h e u n d e r l y i n g cause o f t h e t i n n i t u s , its d u r a t i o n , p i t c h a n d
l o u d n e s s , a n d t h e h e a r i n g l e v e l i n t h e a f f e c t e d ear. S i l v e r s t e i n
5
e t a l . r e p o r t e d t i n n i t u s i m p r o v e m e n t i n 4 7 % o f treated ears, m o s t l y
i n patients w i t h M e n i e r e ' s disease, u s i n g various I T corticosteroid
preparations. A g a i n , theirs was an u n c o n t r o l l e d study. Clearly a
d o u b l e - b l i n d e d , c o n t r o l l e d , c r o s s o v e r t r i a l i s n e e d e d t o assess p r o p -
erly the efficacy of IT steroids for tinnitus.

MENIERE'S DISEASE
M o s t patients w i t h M e n i e r e ' s disease c a n g a i n s y m p t o m a t i c c o n -
trol of their vertigo through conservative medical management. For
Intratympanic Pharmacotherapy 19

those w h o fail, m o r e invasive treatment is indicated. Labyrinthec-


t o m y , a l t h o u g h h i g h l y effective, results i n c o m p l e t e loss o f b o t h a u -
d i t o r y a n d v e s t i b u l a r f u n c t i o n i n t h e o p e r a t i v e ear. C o n s e q u e n t l y ,
t h i s t r e a t m e n t i s o n l y u s e f u l i n n o n s e r v i c e a b l e h e a r i n g ears. E n -
d o l y m p h a t i c sac s u r g e r y ' s g r e a t e s t a d v a n t a g e o v e r o t h e r i n v a s i v e
p r o c e d u r e s i s that, w h e n s u c c e s s f u l , there i s n o loss o f either a u -
ditory or vestibular function. H o w e v e r it remains a controversial
p r o c e d u r e , a n d d e s p i t e success rates t h a t v a r y w i d e l y f r o m center
to center, its o v e r a l l l o n g - t e r m success rate in c o n t r o l l i n g vertigo is
p r o b a b l y 6 0 % t o 7 0 % a t best. Selective v e s t i b u l a r n e u r e c t o m y i s
the gold standard surgical procedure to w h i c h we need to compare
results of p a r t i a l l y d e s t r u c t i v e p r o c e d u r e s , s u c h as selective or par-
tial chemical labyrinthectomy. Vertigo control in vestibular neurec-
t o m y approaches 9 0 % t o 9 5 % i n m o s t series, w i t h o n l y a l o w r i s k
to hearing. H o w e v e r , there is often considerable m o r b i d i t y associ-
ated w i t h t h e c r a n i o t o m y a n d a s u b s t a n t i a l m o n e t a r y cost to the
p a t i e n t or h e a l t h care p r o v i d e r .
I n a n a t t e m p t t o c o n t r o l v e r t i g o w h i l e m i n i m i z i n g h e a r i n g loss
a n d other m o r b i d i t y associated w i t h the invasive treatments, c l i n i -
cians have exploited the k n o w n ototoxicity of aminoglycoside an-
tibiotics. T h e p r o c e d u r e has b e e n called b o t h c h e m i c a l vestibular
ablation (CVA) a n d c h e m i c a l l a b y r i n t h e c t o m y , a l t h o u g h the latter
implies complete destruction of auditory and vestibular function.
C h e m i c a l v e s t i b u l a r a b l a t i o n c a n be t r a c e d as far b a c k as 1948 w h e n
6
F o w l e r prescribed systemic s t r e p t o m y c i n t o treat patients w i t h b i -
7
lateral M e n i e r e ' s disease. S c h u k n e c h t w a s the first to describe IT
injections of aminoglycosides. Using streptomycin, his patients ob-
tained excellent vertigo control but incurred a high incidence of
sensorineural h e a r i n g loss. A l t h o u g h the t e c h n i q u e i n i t i a l l y w e n t
out of favor, E u r o p e a n c l i n i c i a n s w e r e the first to r e i n t r o d u c e it us-
1
i n g I T g e n t a m i c i n i n v a r y i n g dosage s c h e d u l e s .
T h r e e essential m a j o r concepts u n d e r l i e the use of IT a m i n o g l y -
cosides for treating M e n i e r e ' s disease. First, a l t h o u g h a l l a m i n o g l y -
cosides are o t o t o x i c s o m e s u c h a s n e o m y c i n , are m o r e c o c h l e o -
t o x i c , w h e r e a s o t h e r s , s u c h a s s t r e p t o m y c i n a n d g e n t a m i c i n , are
m o r e v e s t i b u l o t o x i c . S e c o n d , g i v e n e n o u g h o f e a c h , t h e y are a l l
b o t h c o c h l e o t o x i c a n d v e s t i b u l o t o x i c . F i n a l l y , t h e r e are t w o o t o -
t o x i c m e c h a n i s m s that seem to a c c o u n t for the treatment's success.
The first and more important is the direct toxic, and most often
8
p e r m a n e n t , effect o n t h e sensory h a i r c e l l s . T h e s e c o n d i s t h e t o x i c
9
effect o n t h e v e s t i b u l a r d a r k c e l l s . T h e s e cells are r e s p o n s i b l e for
e n d o l y m p h p r o d u c t i o n in the vestibular part of the labyrinth.
M a n y clinicians have tried to maximize toxicity to the
vestibular end organ by administering m u l t i p l e g e n t a m i c i n injec-
L.S. Parnés
1 0 - 1 4
tions over consecutive d a y s . A l t h o u g h the results have been
quite good in terms of vertigo control using w h a t I call the "shot
g u n " approach, there is an unacceptably high incidence of hearing
loss ( 2 4 % t o 5 7 % ) . I n a n a t t e m p t t o m i n i m i z e t h i s r i s k t o h e a r i n g ,
1 5 1 6
we, and Hirsch and Kamerer, introduced a weekly "titration"
protocol. T h e concept is that by a l l o w i n g a longer interval between
t r e a t m e n t s i n c o n j u n c t i o n w i t h w e e k l y a u d i o m e t r i c a n d c l i n i c a l as-
sessments earlier a n d potentially reversible detection of hearing
loss m a y be a c h i e v e d . It also a l l o w s for m o r e precise d e t e c t i o n of
the t i m e of onset of vestibular toxicity. W i t h h o l d i n g further treat-
m e n t s a t the first sign o f v e s t i b u l a r t o x i c i t y w o u l d p r e v e n t g e n t a m i -
c i n cochlear toxicity before it ever started.

CURRENT GENTAMICIN ADMINISTRATION TECHNIQUE


A N D PROTOCOL
T h e indications for IT g e n t a m i c i n i n c l u d e all of the f o l l o w i n g : i n -
tractable vertigo spells; a definite diagnosis of unilateral Meniere's
disease a c c o r d i n g t o the criteria o u t l i n e d b y the A m e r i c a n A c a d -
1 7
emy of O p h t h a l m o l o g y - H e a d and Neck Surgery ( A A O - H N S ) ; and
p o o r or no response to s t a n d a r d m e d i c a l measures. T h e degree of
r e s i d u a l h e a r i n g o r v e s t i b u l a r f u n c t i o n i n t h e t r e a t m e n t ear i s n o t a
factor in d e t e r m i n i n g eligibility for g e n t a m i c i n therapy. However,
contralateral deafness or vestibular d y s f u n c t i o n m a y be a contra-
indication, d e p e n d i n g on the specific circumstances.
A l l subjects are m a n a g e d as o u t p a t i e n t s . T h e y r e c e i v e a s i n g l e
0.5-ml to 1-ml dose of buffered g e n t a m i c i n s o l u t i o n weekly, i n i -
t i a l l y for a m a x i m u m o f 4 w e e k s . T h e s o l u t i o n consists o f 0.65 m l
o f s t a n d a r d - s t o c k g e n t a m i c i n s u l p h a t e I.V. ( 4 0 m g / m L ) c o m b i n e d
w i t h 0.35 m L o f 8 . 4 % s o d i u m b i c a r b o n a t e . T h i s m i x t u r e r e s u l t s i n
a g e n t a m i c i n c o n c e n t r a t i o n of 26 m g / m L . Patients are p l a c e d in a
supine position under an operating microscope w i t h their head
t u r n e d a t a n a n g l e o f 4 5 d e g r e e s a w a y f r o m t h e t r e a t m e n t ear, a n d
w i t h the neck fully extended. No sedation is required. The t y m -
panic membrane is anesthetized using a topical application of 1 5 %
p h e n o l at a site just p o s t e r i o r to t h e u m b o t h r o u g h w h i c h a m y r i n -
g o t o m y is d o n e . O t h e r m e t h o d s of t o p i c a l anaesthesia m a y also be
used. A l t h o u g h not absolutely necessary, a 2 . 4 - m m , 30-degree e n -
d o s c o p e i s p a s s e d t h r o u g h t h e o p e n i n g t o v i s u a l i z e t h e m i d d l e ear
s t r u c t u r e s . T h e m a i n i n t e n t i s t o e n s u r e t h a t t h e r e are n o m u c o s a l
folds over the r o u n d w i n d o w niche that m a y impede the contact
of the g e n t a m i c i n in the r o u n d w i n d o w m e m b r a n e . I use a 26-gg,
3.5-inch needle w i t h the sharp end cut off to the 2-inch m a r k on a
1-cc t u b e r c u l i n s y r i n g e f o r t h e i n j e c t i o n .
Intratympanic Pharmacotherapy 21

Initially, the injection was made through a simple needle punc-


ture of the tympanic membrane. Filling the middle ear in the ab-
sence of an escape vent for the air was extremely difficult. It was
impossible to tell, except for inference through a translucent tym-
panic membrane, whether the solution initially or subsequently re-
mained pooled in the round window niche.
The injection proceeds slowly through the myringotomy with
the intent of filling as much of the middle ear space as possible.
Although filling the middle ear during the initial injection is fairly
easy, it is very difficult to ensure that the solution remains in the
target region. It is imperative that the solution pools in the round
window niche so that it remains in contact with the round win-
dow membrane. The volume of solution injected into the middle
ear is relatively unimportant, as very little of the gentamicin will
permeate into the inner ear. The more important factors relating to
inner ear absorption are the concentration of the drug in the solu-
tion and the duration of its contact with the round window
membrane. In most cases, 0 . 3 mL to 0 . 5 mL of solution can be in-
jected into the middle ear space before it extravasates back through
the myringotomy. Patients are left in the supine position with the
head turned for 10 minutes, and the ear is examined again
microscopically.
Despite asking patients to keep the head perfectly still and to
swallow as little as possible, more often than not the fluid disperses
from where it is initially placed. Some of the fluid likely settles
into the more dependent air cells or down the eustachian tube and,
in many cases, it extravasates out of the middle ear into the ear
canal. If required, the middle ear is "topped up" with more solu-
tion and left for another 10 minutes, after which a Baxter beveled
button tube (Xomed) is inserted for the duration of the therapy. The
patient is instructed to protect the ear from water contamination.
All subsequent injections are done similarly to the first, except the
needle is inserted directly through the lumen of the tube into the
middle ear. The Baxter button is preferred because of its bevel
shape, which allows for easy placement of the needle tip into, and
excellent visualization of the middle ear through, its lumen. It is
also made of very soft Silastic, making it easy and almost painless
to remove at the end of the treatments. At the completion of the
treatment, the tube is removed and the tympanic membrane is al-
lowed to heal.
Patients are initially scheduled for four treatments, 1 week
apart. All patients must have an audiogram and ENG within 1
month of the first treatment. Patients are then scheduled for an
audiogram immediately before each subsequent treatment. The end
L.S. Parnés

p o i n t s f o r t h e t r e a t m e n t s are a s f o l l o w s : (1) a s i g n i f i c a n t r e d u c t i o n
in hearing (a drop in pure tone acuity [PTA] of more than 15 dB or
a d r o p in speech d i s c r i m i n a t i o n score [SDS] of m o r e t h a n 1 5 % ) per-
s i s t i n g f o r m o r e t h a n 2 c o n s e c u t i v e w e e k s ; (2) o n s e t o f c o n s t a n t v e s -
tibular symptoms such as dysequilibrium or m o t i o n sensitivity,
v e r y d i f f e r e n t f r o m t h e i r M e n i e r e ' s a t t a c k s ; (3) o n s e t o f a s p o n t a n e -
ous paralytic nystagmus or f l o r i d post-headshake nystagmus that
w a s n o t p r e s e n t b e f o r e t r e a t m e n t ; o r (4) t h e f o u r s c h e d u l e d t r e a t -
m e n t s . If, a f t e r t h e c o m p l e t i o n o f t h i s f i r s t c o u r s e o f t r e a t m e n t , t h e
patient continues to have troublesome vertigo spells, another
course of treatment m a y be considered. However, if the first course
d i d not result in any significant reduction in the caloric response,
and if there were no obvious anatomical or technical problems dur-
ing the i n i t i a l injections, I w o u l d t h e n offer surgical i n t e r v e n t i o n
rather than more IT gentamicin.

RESULTS
To date, I have treated 83 patients using this titration p r o t o c o l , of
w h o m 68 have been available for detailed f o l l o w - u p assessments.
T h e r e w e r e 3 5 w o m e n a n d 3 3 m e n , w i t h a n a v e r a g e age o f 5 4 . 6
y e a r s ( r a n g e 3 2 - 8 3 y e a r s ) . T h e s u b j e c t s r e c e i v e d a n a v e r a g e o f 3.6
i n j e c t i o n s ( r a n g e 1—8).

Vertigo
1 7
The A A O - H N S r e c o m m e n d e d formula for calculating vertigo
control was used. The formula is as follows:

Vertigo Control = (X/Y) X 100,

w h e r e X is the average n u m b e r of d e f i n i t i v e spells per m o n t h for


the 6 - m o n t h p e r i o d o c c u r r i n g 1 8 t o 2 4 m o n t h s after g e n t a m i c i n
therapy, a n d Y is the average n u m b e r of d e f i n i t i v e spells per m o n t h
for the 6 months before treatment. Six patients d i d not gain
adequate vertigo control f r o m the gentamicin treatment and under-
w e n t labyrinthectomy or vestibular neurectomy before 24 m o n t h s
h a d elapsed. For these i n d i v i d u a l s , vertigo c o n t r o l was calculated
u s i n g the average n u m b e r of vertigo attacks they e x p e r i e n c e d per
m o n t h f r o m t h e i r last g e n t a m i c i n i n j e c t i o n u n t i l surgery. Fifty-
seven of t h e 68 patients ( 8 4 % ) w e r e c o m p l e t e l y free of attacks
( A A O - H N S class A ) a n d f o u r p a t i e n t s ( 6 % ) h a d s u b s t a n t i a l c o n t r o l
o f t h e i r v e r t i g o (class B ) . O n e o f t h e 6 8 p a t i e n t s c o n t i n u e d t o h a v e
vertigo at a p p r o x i m a t e l y the same frequency as before the gentami-
c i n t r e a t m e n t (class D ) ; h o w e v e r , she e l e c t e d n o t t o h a v e a n y fur-
ther invasive treatments. As already noted, six patients (9%) h a d
Intratympanic Pharmacotherapy 23

poor vertigo control after gentamicin therapy and required second-


ary surgical treatment (class F).
Hearing
A deterioration in PTA (500 Hz, 1000 Hz, 2000 Hz, 3 0 0 0 Hz) of
more than 10 dB was considered a clinically significant hearing
loss. A pure tone average (PTA) decrease of more than 30 dB was
classified as an extreme hearing loss. A change of less than 10 dB
was considered clinically insignificant. A deterioration or improve-
ment of more than 1 5 % in SDS was considered clinically sig-
nificant.
A 6-month follow up audiogram is likely a true indicator of
induced ototoxicity from the gentamicin. The 6-month audiogram
was not available for three of the 68 patients. Of the remaining 65
patients, 51 ( 7 8 % ) had no change in their PTA and nine patients
( 1 4 % ) had a clinically significant improvement in their PTA. In
comparison, only five patients ( 8 % ) experienced a deterioration in
their PTA during this period. Moreover, none of the patients expe-
rienced an extreme hearing loss (more than 30 dB) during this in-
terval. Of the 60 patients ( 9 2 % ) with either no change or an im-
provement in PTA, 57 ( 9 5 % ) also had either an improved or un-
changed SDS, whereas three subjects ( 5 % ) had a reduction in SDS.

Caloric Responses
Sixty-two of the 68 patients had both pre- and post-gentamicin ENG
assessments. The mean caloric response before therapy in the
treated ears was 24 7s (range 5 - 5 0 7 s ) . After gentamicin treatment,
the average response decreased to 7 7s (range 0 - 4 0 7 s ) . In com-
paring caloric function from before and after the gentamicin injec-
tions, patients were classified into four groups. Twelve of the 62
subjects displayed posttreatment caloric responses between 5 0 %
to 1 0 0 % of their pretreatment score (group 1). Twelve patients dem-
onstrated posttreatment responses between 1 0 % and 5 0 % of their
pretreatment value (group 2). Ten subjects ( 1 6 % ) displayed less
than 1 0 % of their pretreatment caloric responses on posttreatment
assessment (group 3). This group also included those subjects who
responded to ice water stimulus only. Twenty-eight patients ( 4 5 % )
displayed a completely absent ice water caloric response after gen-
tamicin therapy (group 4).
Overall, there was a significant association (P < .05) between
reduction in caloric response and improvement in vertigo control.
Of the seven patients who did not obtain either complete or sub-
stantial vertigo control, four were in group 1, one was in group 2,
and one was in group 3. In one case, the continued severity of the
24 L.S. Parnes
Meniere's attacks w a r r a n t e d t i m e l y surgical i n t e r v e n t i o n , a n d c o n -
sequently no follow-up E N G testing was possible.

DISCUSSION
Using the titration protocol, 8 4 % of patients were completely
relieved of their Meniere's vertigo attacks, whereas an a d d i t i o n a l
6 % o b t a i n e d substantial c o n t r o l . T h i s 9 0 % success rate c o m p a r e s
1 0 , 1 4
favorably w i t h the results of the shot-gun protocol s t u d i e s .
T h i s v a l u e also compares favorably w i t h the results f r o m vestib-
1 8 1 9
ular n e u r e c t o m y . ' As for the hearing results, at the 6 - m o n t h
f o l l o w - u p , only five patients (8%) h a d a hearing drop, whereas a
larger n u m b e r (nine patients) h a d actually s h o w n a n i m p r o v e -
m e n t . These results far e x c e e d those of t h e s h o t - g u n studies.
Perhaps most important, using the titration protocol, there were
n o cases o f e x t r e m e h e a r i n g l o s s ( m o r e t h a n 3 0 d B ) , a s c o m p a r e d
w i t h the 1 0 % t o 2 4 % incidence associated w i t h the shot-gun
1 0 1 4
technique. "
W h e t h e r t h e results w i t h s t a n d t h e test o f t i m e r e m a i n s t o b e
seen. Because t h e rate of h e a r i n g loss is so l o w , no bridges w i l l h a v e
been b u r n e d for the treatment failures. M o r e g e n t a m i c i n can always
b e i n j e c t e d ; c o n v e r s e l y , a l l t h r e e t y p e s o f s u r g e r y (sac s u r g e r y ,
neurectomy, labyrinthectomy) remain viable options depending on
the degree of r e s i d u a l hearing a n d vestibular f u n c t i o n . U n d o u b t -
edly, a p a t i e n t e v e n t u a l l y m a y r e s p o n d w i t h an i d i o s y n c r a t i c reac-
t i o n to gentamicin, as others have described (personal c o m m u n i -
cation). T h a t is, a n i r r e v e r s i b l e e x t r e m e h e a r i n g loss m i g h t o c c u r
after one o r t w o I T i n j e c t i o n s . Based o n m y e x p e r i e n c e t o date, the
chances o f t h i s o c c u r r i n g w i t h t h e t i t r a t i o n p r o t o c o l are e x t r e m e l y
s m a l l , a n d p r o b a b l y n o greater t h a n the e x t r e m e h e a r i n g loss that
might occur w i t h vestibular neurectomy, the gold standard com-
parative treatment. As such, I strongly r e c o m m e n d IT gentamicin
t i t r a t i o n injections as the first l i n e i n t e r v e n t i o n a l treatment for i n -
tractable M e n i e r e ' s disease.

INFLAMMATORY INNER EAR DISORDERS


A u t o i m m u n e (e.g., C o g a n ' s s y n d r o m e ) a n d o t h e r i n f l a m m a t o r y i n -
n e r ear diseases m a y ravage t h e l a b y r i n t h i f n o t treated aggressively
w i t h a n t i - i n f l a m m a t o r y m e d i c a t i o n . C o r t i c o s t e r o i d s are t h e m a i n -
stay of treatment, yet p a r t l y because of the existence of the b l o o d -
l a b y r i n t h i n e barrier, the ideal drug, dose, a n d route of administra-
2 0
t i o n are c u r r e n t l y u n k n o w n . I n a r e c e n t s t u d y , cochlear fluid
pharmacokinetic profiles of hydrocortisone, methylprednisolone,
a n d d e x a m e t h a s o n e w e r e established i n the g u i n e a p i g after oral,
intravenous, and IT administration. High-performance liquid chro-
Intratympanic Pharmacotherapy 25

matography was used to determine the drug concentrations, and


comparisons were made w i t h simultaneous pharmacokinetic pro-
files f r o m b l o o d a n d c e r e b r o s p i n a l f l u i d . T h e f i n d i n g s d e m o n s t r a t e d
a m u c h higher penetration of all three drugs into the cochlear flu-
ids after I T a p p l i c a t i o n a s c o m p a r e d w i t h systemic a d m i n i s t r a t i o n ,
w i t h m e t h y l p r e d n i s o l o n e s h o w i n g t h e best p r o f i l e . T h e results sug-
gest t h a t I T a d m i n i s t r a t i o n o f c o r t i c o s t e r o i d s m i g h t b e m o r e e f f i c a -
cious, w h i l e a v o i d i n g h i g h b l o o d levels, a n d therefore the delete-
r i o u s side effects of s y s t e m i c use.
I n t r a t y m p a n i c a p p l i c a t i o n of corticosteroids for the manage-
m e n t o f i n f l a m m a t o r y i n n e r ear d i s o r d e r s i s t r u l y a b u r g e o n i n g
2 1
field. Shea a n d G e recently p u b l i s h e d favorable results using
c o m b i n e d systemic a n d I T d e x a m e t h a s o n e for M e n i e r e ' s disease.
Conversely, Silverstein (H. Silverstein, personal communication)
h a s h a d less f a v o r a b l e r e s u l t s . I n t h a t M e n i e r e ' s d i s e a s e i s b o t h a
chronic and recurrent disorder, w i t h an allergic/inflammatory
p a t h o p h y s i o l o g y a c c o u n t i n g f o r o n l y a m i n o r i t y o f cases, t o t h i s
author, treatment w i t h corticosteroids seems i n a p p r o p r i a t e . A
double-blind controlled study comparing IT corticosteroids w i t h a
placebo w o u l d help to validate or dispel the idea.
I n n e r ear g l u c o c o r t i c o i d r e c e p t o r s h a v e b e e n i d e n t i f i e d i n d i f -
2 2 , 2 3 2 4
ferent a n i m a l m o d e l s . Rarey a n d C u r t i s substantiated this
finding in h u m a n cadaveric temporal bones. T h e y identified recep-
tors in b o t h the cochlear a n d vestibular tissues, w i t h the highest
concentration of receptors f o u n d in the spiral ligament. These f i n d -
ings l e n d credence to the v e r y n o t i o n of u s i n g steroids to treat i n -
f l a m m a t o r y i n n e r ear d i s o r d e r s , w h e t h e r s y s t e m i c a l l y o r i n t r a t y m -
p a n i c a l l y . T h a t t r a n s t y m p a n i c a p p l i c a t i o n a l l o w s f o r a h i g h e r or-
d e r o f m a g n i t u d e o f i n n e r ear d r u g c o n c e n t r a t i o n , a s d e m o n s t r a t e d
i n o u r p r e v i o u s a n i m a l study, o n l y strengthens its p o t e n t i a l s a l u -
tary clinical application.

INTRATYMPANIC CORTICOSTEROID EXPERIENCE


S i n c e 1 9 9 2 , I h a v e t r e a t e d 3 7 p a t i e n t s w i t h v a r i o u s i n n e r ear d i s -
orders using IT corticosteroids. T h e first 20 patients were treated
w i t h dexamethasone, three of w h o m were eventually crossed over
to m e t h y l p r e d n i s o l o n e . Because of the a n i m a l study findings, the
17 more recent patients were treated w i t h methylprednisolone.
Treatments to date have been directed o n l y at the sensory hearing
loss r e s u l t i n g f r o m t h e d i s o r d e r s . Patients h a v e p r e s e n t e d w i t h
variable levels of acute or subacute, unilateral or bilateral sensori-
n e u r a l h e a r i n g l o s s e s , s o m e w i t h p r e - e x i s t i n g i n n e r ear d i s e a s e s .
Vertigo a n d t i n n i t u s , w h i c h w e r e seen i n m a n y o f these patients,
w e r e n o t t h e target s y m p t o m s o f this treatment.
L.S. Parnés

T h e m a i n i n d i c a t i o n for treatment was a relatively n e w onset


u n i l a t e r a l , o r i n o n e case b i l a t e r a l , s e n s o r i n e u r a l h e a r i n g l o s s f r o m
a disorder k n o w n to r e s p o n d to systemic corticosteroids, or other-
wise not k n o w n to respond to conventional treatment. Patients
w i t h clinical cochlear e n d o l y m p h a t i c hydrops were treated c o m -
pletely by speculation. A l l patients, particularly those early in this
series, w e r e i n f o r m e d that this w a s a n e w treatment. T e c h n i c a l l y ,
the m e t h o d of injection was identical to a standard clinical tech-
n i q u e ( I T g e n t a m i c i n f o r M e n i e r e ' s d i s e a s e ) , u s i n g safe s t a n d a r d
medications (corticosteroids) not k n o w n to be ototoxic.
Clinical Material
As s h o w n in Table 1, the treated disorders were g r o u p e d into eight
general categories. S o m e disorders clearly r e s p o n d e d to treatment
more favorably than others.
Six patients underwent IT corticosteroid injections in only
h e a r i n g e a r s , t w o o f w h o m a r e d e t a i l e d i n t h e f o l l o w i n g case r e -
ports. T h e reports serve to h i g h l i g h t b o t h the safety a n d efficacy of
the technique.

TABLE 1.
B r e a k d o w n of Patients Undergoing
Intratympanic Corticosteroid Treatments

N u m b e r of Number
Disorders Patients Improved
S u d d e n deafness 13 7
Cochlear hydrops 8 0
Sudden drop in 7 0
pre-existing
h e a r i n g loss
Surgically induced 3 3
Cogan's s y n d r o m e 2 2
Delayed 2 0
postmeningitis
A u t o i m m u n e inner 1 1
ear d i s e a s e
Ramsay H u n t 1 0
syndrome
Totals 37 13
Intratympanic Pharmacotherapy 27
CASE REPORT 1 . — A 2 6 - y e a r - o l d w o m a n p r e s e n t e d i n A u g u s t o f 1 9 9 0
w i t h a l e f t - s i d e d s e n s o r i n e u r a l h e a r i n g loss [ s p e e c h r e c e p t i o n
t h r e s h o l d (SRT) 60 d B ; SDS 5 2 % ] w h i c h progressed over several
week s . She w a s also n o t e d to h a v e an isolated h i g h f r e q u e n c y
( > 3 k H z ) s e n s o r i n e u r a l l o s s i n t h e r i g h t ear. S h e c o m p l a i n e d o f v e r -
tigo, a n d vestibular testing s h o w e d an absent caloric response in
t h e l e f t ear. A c o m p l e t e w o r k u p f o r r e t r o c o c h l e a r a n d s y s t e m i c d i s -
ease w a s n e g a t i v e , a n d s h e w a s s t a r t e d o n p r e d n i s o n e , 6 0 m g d a i l y .
A l t h o u g h there was no i m p r o v e m e n t , d u r i n g the next m o n t h her
h e a r i n g r e m a i n e d stable a n d her p r e d n i s o n e w a s s l o w l y tapered t o
30 mg/day.
S o o n after, p o l y a r t h r i t i s d e v e l o p e d w i t h a h i g h l y e l e v a t e d
e r y t h r o c y t e s e d i m e n t a t i o n rate (ESR). T h e 3 0 m g / d a y dose o f p r e d -
n i s o n e w a s m a i n t a i n e d . O n e m o n t h later, t h e p a t i e n t h a d a s p l e n i c
i n f a r c t d e v e l o p i n c o n j u n c t i o n w i t h a f u r t h e r d e c l i n e i n h e r hear-
i n g i n b o t h ears. T h e l e f t ear b o t t o m e d o u t t o t h e p r o f o u n d l e v e l ,
w h e r e a s t h e r i g h t ear d r o p p e d t o a 4 5 - d B l e v e l i n t h e l o w f r e q u e n -
cies w h i l e m a i n t a i n i n g a 1 0 0 % SDS. She also b e c a m e e x t r e m e l y
vertiginous.
T h e presumptive diagnosis of systemic vasculitis was treated
by increasing her p r e d n i s o n e dose to 80 m g / d a y a n d starting her
o n m o n t h l y pulse treatments o f c y c l o p h o s p h a m i d e , 750 m g . O n
t h i s r e g i m e n , h e r h e a r i n g i n t h e r i g h t ear g r a d u a l l y i m p r o v e d o v e r
1 m o n t h to the original level, except for an isolated but persistent
h i g h f r e q u e n c y loss. T h e left p r o f o u n d h e a r i n g loss n e v e r recov-
ered. W h i l e o n t h e h i g h dose o f p r e d n i s o n e , she h a d b i l a t e r a l o c u -
lar i n f l a m m a t i o n develop. T h e ophthalmologists i d e n t i f i e d a bilat-
eral n o n s y p h i l i t i c interstitial keratitis a n d the diagnosis of Cogan's
s y n d r o m e was made w i t h certainty.
D u r i n g the next 3 months, the patient's prednisone was s l o w l y
tapered to 25 mg/day w h i l e her hearing was closely monitored. In
M a r c h 1 9 9 1 , she presented w i t h another p r e c i p i t o u s 30-dB d r o p i n
h e r b o n e l e v e l s i n h e r r i g h t ear, a s w e l l a s a n i n c r e a s e i n t h e d i z z i -
ness. T h e p r e d n i s o n e w a s i n c r e a s e d t o 5 0 m g / d a y a n d h e r h e a r i n g
i m p r o v e d to the baseline level during the next m o n t h . Her keratitis
flared up at this p o i n t a n d she was g i v e n azathioprine, 100 mg/day.
On this n e w regimen, the systemic component seemed w e l l
c o n t r o l l e d . Other t h a n persistent b u t u n e x p l a i n e d left otalgia, there
were no n e w problems. Gradually, during a 6-month period, the
p r e d n i s o n e was tapered to a m a i n t e n a n c e dose of 12 m g / d a y a n d
the azathioprine was m a i n t a i n e d at 100 mg/day.
I n June o f 1992, the p a t i e n t presented w i t h severe a b d o m i n a l
d i s c o m f o r t that, after i n v e s t i g a t i o n , w e n t u n d i a g n o s e d . H e r p r e d -
L.S. Parries

nisone dose w a s s l o w l y l o w e r e d so that by July of 1993, she was


receiving 7 m g / d a y . A l l the w h i l e , her hearing r e m a i n e d stable. In
January 1994, w h i l e t a k i n g the same dose of p r e d n i s o n e , her hear-
i n g d r o p p e d s u d d e n l y b y 2 5 d B . A l t h o u g h she n o w h a d severe
c u s h i n g o i d features, m a r k e d osteoporosis a n d early signs o f cata-
racts, the p r e d n i s o n e dose was increased to 30 mg/day. D u r i n g the
next week her hearing i m p r o v e d by 15 dB, at w h i c h point the pred-
nisone dose was decreased to 20 mg/day.
Understandably, the patient was extremely concerned about
the systemic manifestations of the prednisone. In that hearing fluc-
t u a t i o n w a s her o n l y o n g o i n g p r o b l e m , she c o n s i d e r e d s t o p p i n g the
p r e d n i s o n e , aware o f the fact that i t m i g h t result i n p r o f o u n d bilat-
eral deafness. It w a s at t h i s p o i n t t h a t I first c o n s i d e r e d u s i n g IT cor-
ticosteroid injections. N o t h i n g h a d appeared yet in the literature on
t h e use o f I T c o r t i c o s t e r o i d s for i n f l a m m a t o r y i n n e r ear d i s o r d e r s ,
and using an u n p r o v e n technique w i t h possible u n k n o w n detri-
m e n t a l effects i n a n o n l y h e a r i n g ear s e e m e d e x t r e m e l y r i s k y . H o w -
ever, after a l e n g t h y d i s c u s s i o n a b o u t the p o t e n t i a l risks a n d b e n -
efits of t h e t r e a t m e n t , she e l e c t e d to p r o c e e d . I a r b i t r a r i l y c h o s e
dexamethasone as the corticosteroid for injection. Because the
standard-stock s o l u t i o n of 4 m g / m L was too viscous for injecting
i n t o t h e m i d d l e ear, i t w a s d i l u t e d b y o n e h a l f u s i n g n o r m a l s a l i n e .
Arbitrarily, treatments co m m enced weekly. A Baxter beveled
b u t t o n t y m p a n o s t o m y t u b e ( X o m e d ) w a s p l a c e d i n t h e p o s t e r i o r as-
pect of the t y m p a n i c m e m b r a n e to serve as a c o n d u i t for d r u g i n -
stillation. T h e p r e d n i s o n e dose was r a p i d l y decreased to the m a i n -
tenance level of 7 mg/day. After three treatments, hearing acuity
returned to the original baseline. Weekly treatments d u r i n g the next
2 m o n t h s stabilized her hearing. A t t e m p t s to increase the interval
b e t w e e n treatments b e y o n d 10 days i n v a r i a b l y resulted in a sig-
n i f i c a n t d r o p i n h e a r i n g . W h e n s h e r e t u r n e d 2 w e e k s a f t e r t h e sec-
o n d 2-week interval dose, her hearing h a d d r o p p e d by 10 dB. Af-
ter another treatment, her h e a r i n g recovered to baseline, a n d three
more 10-day interval treatments were given. Another attempt was
m a d e to stretch the interval to 2 weeks, but again her hearing
d r o p p e d , t h i s t i m e b y 2 0 d B , the day before the s c h e d u l e d treat-
ment. Ten-day interval treatments c o m m e n c e d again, a n d by the
t h i r d treatment, her hearing had returned to baseline.
Because of unanticipated scheduling difficulties in the s u m m e r
of 1994, one treatment i n t e r v a l w a s as l o n g as 27 days. On that oc-
casion her h e a r i n g acuity (SRT) d r o p p e d by 35 d B . In an attempt
t o r e c o v e r l o s t h e a r i n g , m o r e a g g r e s s i v e d o s i n g w a s b e g u n , a s of-
ten as twice weekly. In spite of this change, thresholds continued
Intratympanic Pharmacotherapy 29

to fluctuate at the 35-dB to 40-dB level for the n e x t 4 m o n t h s . Co-


i n c i d e n t l y she h a d a flare-up of her interstitial keratitis. T h i s was
m a n a g e d w i t h t o p i c a l corticosteroid eye drops. In a d d i t i o n , a n e w
p r o b l e m arose, that b e i n g severe a b d o m i n a l p a i n w h i c h , d e s p i t e ex-
tensive investigation, remained undiagnosed. As a result, the oral
prednisone dose was briefly increased, w h i c h in t u r n seemed to
h e l p stabilize her hearing. By December her hearing h a d again re-
covered to the baseline level. In February 1995, the interstitial kera-
titis flared up again as d i d the a b d o m i n a l p a i n . T h e r e w a s also an-
other precipitous drop in her hearing by 40 dB. The IT dexameth-
asone injections, w h i c h w e r e c o n t i n u i n g at w e e k l y intervals, were
increased to twice weekly treatments and her oral prednisone was
again b u m p e d up to 40 m g / d a y for a s h o r t 2 - w e e k burst. H e r hear-
ing gradually returned to baseline. There was a similar recurrence
i n A u g u s t / S e p t e m b e r , this t i m e associated w i t h severe h y p e r t e n -
sion. T h e oral p r e d n i s o n e dose was t e m p o r a r i l y increased again.
By January 1996, her systemic disease seemed quiescent
despite a c o n t i n u a l l y m a r k e d l y elevated ESR, a n d her hearing re-
m a i n e d at baseline. T h e p r e d n i s o n e m a i n t e n a n c e dose was n o w 11
m g / d a y a n d she w a s a t t e n d i n g w e e k l y for IT dexamethasone injec-
t i o n s . B a s e d o n t h e r e s u l t s f r o m o u r a n i m a l s t u d y , a n d i n a n at-
tempt to reduce the n u m b e r of clinic visits, we elected to change
the injection drug f r o m dexamethasone to methylprednisolone. I
used the M e d r o l intravenous solution, 40 m g / m L , w h i c h is the low-
est c o n c e n t r a t i o n o f t h e s t a n d a r d - s t o c k m e t h y l p r e d n i s o l o n e s o l u -
tions. Unfortunately, unlike the dexamethasone w h i c h caused little
discomfort, this preparation i n d u c e d significant b u r n i n g otalgia
that lasted several hours f r o m the t i m e of injection. T h e a d d i t i o n
o f 0.1 m L o f 1 % p l a i n l i d o c a i n e t o 0 . 9 m L o f t h e m e t h y l p r e d -
nisolone s o l u t i o n h e l p e d to lessen the discomfort significantly. I
have since used the same m i x t u r e for all subsequent injections in
this, and all other patients. Since starting w i t h the methylpred-
n i s o l o n e , the patient has h a d no further m a j o r drops in hearing.
S h e n o w a t t e n d s c l i n i c e v e r y 2 t o 2V2 w e e k s f o r t r e a t m e n t s , a n d
her hearing, as of M a y 1997, is still at the SRT level of 10 dB w i t h
9 6 % SDS. In June of 1997, she u n d e r w e n t e x t r a c t i o n of a r i g h t cata-
ract resulting f r o m her p r o l o n g e d course of systemic corticoste-
r o i d s . She is c u r r e n t l y u n d e r t h e care of o u r o r t h o p e d i c surgeons
w i t h p r o v e n avascular necrosis of b o t h hips. Her ESR remains
m a r k e d l y elevated.
CASE REPORT 2 . — A 3 6 - y e a r - o l d w o m a n , w h o l i v e d a c o n s i d e r a b l e
distance f r o m o u r center, presented i n M a r c h 1994 w i t h bilateral
L.S. Parnés

sensorineural hearing loss. The right hearing loss, which occurred


in 1 9 9 1 , was sudden, profound, and permanent. The left hearing
loss began 2 months before presentation and was mild and gradual.
Vertigo was not a feature of her disorder. Her medical history was
otherwise unremarkable. The physical examination was negative
other than for the hearing loss. The audiogram showed a profound
sensorineural loss in the right ear. On the left, there was a 30-dB
sensorineural loss, SDS of 9 6 % and absent acoustic reflexes. Tem-
poral bone and brain imaging was negative, as was the workup for
systemic immune disease, including syphilis serology.
A trial of systemic corticosteroids was recommended. The great
distance from her home to our center initially precluded the IT ste-
roid injections. After a course of oral prednisone, 40 mg/day for 2
weeks then 20 mg/day for 2 weeks, her left hearing loss completely
recovered, but the profound right loss persisted. The prednisone
was then decreased to 10 mg/day for 2 weeks, at which time her
hearing dropped by 10 dB. Her local otolaryngologist advised her
to increase the dose again by at least 20 mg/day, but she was re-
luctant to do so, due to the unpleasant side effects. She claimed
that the drug induced troublesome hair loss.
She was referred to me again, and I initiated a trial of IT dexa-
methasone injections. Four injections of 2 mg/mL were given, each
spaced by 1 week. The oral prednisone was initially increased to
20 mg/day for 1 week, then tapered by 5 mg weekly. The left ear
responded, and gradually her auditory thresholds returned to nor-
mal. The injections were then assumed by her local otolaryngolo-
gist. Weekly, and eventually biweekly, injections were given with
her hearing remaining stable. The injections allowed for complete
cessation of the oral prednisone.
The injection interval was increased to 1 month. Three weeks
after the second injection, her hearing abruptly dropped by 40 dB.
After resumption of weekly injections and restarting her pred-
nisone at 40 mg/day, the hearing loss slowly recovered. Another
attempt to increase the interval between injections resulted in an-
other 40-dB hearing loss. The hearing recovered with another boost
of prednisone and twice weekly middle ear injections. Once the
hearing stabilized, the prednisone was withdrawn. For the next 8
months, the patient received IT dexamethasone injections every 3
weeks, alternating between her own hometown otolaryngologist
and myself. Because her hearing remained completely normal,
when her tube finally extruded in January 1996, treatment was dis-
continued. Two weeks later, her hearing worsened by 40 dB. This
time she was treated only with IT dexamethasone.
Intratympanic Pharmacotherapy 31
Treatments commenced weekly for a month, then every 2
weeks for 2 months, and her hearing returned to normal. At this
point, the patient requested that the treatments be stopped. During
the next 2 months, the hearing dropped again by 40 dB. Biweekly
IT injections were reinstituted, this time using methylpred-
nisolone. After two treatments, her hearing returned to normal.
Gradually the treatment intervals were lengthened to as long
as 6 weeks. Because her hearing remained stable, the treatments
were stopped in January 1997. Two months later, her hearing
dropped by 50 dB. Treatment with IT dexamethasone was initiated
at the patient's request because of the discomfort induced by meth-
ylprednisolone. After four weekly and then two biweekly treat-
ments, the hearing returned to its current level of an S R T of 10 dB
and SDS of 9 6 % . Again, prednisone was not used.

Results
Table 2 details the 13 patients who were treated for sudden senso-
rineural deafness, one of whom had bilateral involvement and
treatment. S i x patients showed a significant improvement in audi-
tory thresholds, five progressing from a severe/profound loss to
relatively normal hearing thresholds.
One patient (RB.) presented 3 weeks after a bilateral sudden
hearing loss, with associated vertigo. He had been initially man-
aged elsewhere with conventional medical measures, yet his hear-
ing continued to deteriorate. Intratympanic methylprednisolone
abruptly halted the progression of his hearing loss and eventually,
over the long term, led to a slight hearing improvement, especially
in his S D S ' s . As seen in Table 2, his treatments were notably more
numerous than the other patients in this group. On repeated occa-
sions, after stopping the treatments, his auditory thresholds
dropped slightly, along with a significant subjective drop in hear-
ing. When the treatments resumed, there would be objective and
subjective improvement. Eventually the problem burned itself out,
allowing for cessation of therapy. At no time did this patient re-
ceive systemic corticosteroids.
Most of the patients in this group received treatment early af-
ter the onset of hearing loss. Although the numbers are small, there
seemed to be no correlation between the time of treatment after the
onset of hearing loss, the drug used, the number of treatments, and
the final hearing result.
Unlike the sudden idiopathic hearing loss group, the seven
patients with subacute unilateral deterioration of a pre-existing bi-
lateral sensorineural loss all did uniformly poorly. Although none
TABLE 2.
Sudden Hearing Loss Group [n = 13]

Interval Between Hearing Before


Onset of Hearing Vestibular N u m b e r of Treatments SRT; Hearing after
Patient Age/Sex Loss a n d Treatment Symptoms Drug Treatments SDS Treatments

JP 47 F 1 Wk Yes Dex 8 80 dB; 1 2 % NC


AF 56 M 3 Wks after CABG No Dex 4 100 dB; 0 % 5 dB; 9 6 %
HN 45 F 4 WkS No Dex 5 55 dB; 5 6 % NC
TF 25 F 2 Days No Dex 4 85 dB; 1 2 % 0 dB; 1 0 0 %
WP 57 M 1 Wk No Meth 6 85 dB; 0 % NC
AL 44 F 1 Wk Mild Meth 6 60 dB; 2 0 % 5dB; 9 6 %
JZ 49 M 6 Wks No Meth 2 75 dB; 0 % NC
GH 65 F 2 Wks No Meth 6 30 dB; 8 4 % NC
VM 53 F 1 Wk No Meth 2 NR 30 dB; 1 0 0 %
HM 70 M 1.5 Wks No Meth 6 NR 45 dB; 5 4 %
RS 50 M 1 Wk Yes Meth 6 NR NC
HB 21 F 3 Days Yes Meth 7 NR 25 dB; 8 8 %
PB 29 M 3 Wks Yes Meth 29 AU AS 80 dB; 2 0 % AS 85 dB; 6 8 %
AD 70 dB; 3 6 % AD 55 dB; 7 6 %
Abbreviations: SRT, speech reception threshold; SDS, speech discrimination score; Dex, dexamethasone; Meth, methylprednisolone;
CABG, coronary artery bypass graft; NR, no response; JVC, no change.
Intratympanic Pharmacotherapy 33

s h o w e d a n y h e a r i n g i m p r o v e m e n t , neither d i d they s h o w a n y sig-


nificant worsening in auditory thresholds directly attributed to the
treatments.
Of the eight patients w i t h cochlear hydrops, none s h o w e d any
significant h e a r i n g i m p r o v e m e n t d u r i n g o r i m m e d i a t e l y after t h e
treatments. One patient realized a hearing improvement, but this
o c c u r r e d 3 m o n t h s after t h e cessation o f t r e a t m e n t . A l l patients h a d
a relatively n e w onset, low-frequency, u p - s l o p i n g sensorineural
h e a r i n g l o s s i n t h e t r e a t m e n t ear. F o u r h a d e v i d e n c e o f u n i l a t e r a l
involvement, whereas four had bilateral findings w i t h a pré-
e x i s t e n t h e a r i n g l o s s i n t h e c o n t r a l a t e r a l ear. N o p a t i e n t s h a d e v e r
h a d v e r t i g o s p e l l s a r i s i n g f r o m t h e t r e a t m e n t ear b e f o r e t h e o n s e t
of treatment. I used o n l y unilateral treatments for all patients in
this group. T w o patients h a d their first spells of vertigo d u r i n g the
IT treatments. T w o others began h a v i n g vertigo attacks afterward,
o n e p a t i e n t , 2 m o n t h s later a n d t h e other, 1 year later.
T h e three p a t i e n t s w i t h p o s t o p e r a t i v e h e a r i n g loss h a d a l l u n -
dergone posterior semicircular canal occlusion for intractable be-
nign paroxysmal positional vertigo. A l l three had persisting 20 dB
to 30 dB s e n s o r i n e u r a l h e a r i n g losses 6 to 8 w e e k s after t h e i r sur-
gery. I n m o s t p a t i e n t s , t h i s a n t i c i p a t e d h e a r i n g loss, w h i c h l i k e l y
results f r o m a surgically i n d u c e d aseptic labyrinthitis, resolves
w i t h i n 3 to 4 w e e k s after surgery. These three patients each h a d
c o m p l e t e h e a r i n g r e c o v e r y after three d e x a m e t h a s o n e treatments
spaced over a 1-week interval.
T h e t w o patients w i t h l o n g d e l a y e d p o s t m e n i n g i t i c h e a r i n g loss
f a i l e d t o r e s p o n d t o t r e a t m e n t s . T h e ear s u f f e r i n g f r o m R a m s a y -
H u n t s y n d r o m e also s h o w e d n o response t o treatment. I n fact, de-
spite h a v i n g u n d e r g o n e t w o d e x a m e t h a s o n e t r e a t m e n t s , the hear-
i n g loss c o n t i n u e d to progress f r o m a m o d e r a t e to a p r o f o u n d loss
over the subsequent 6 weeks.
A l t h o u g h representing a very small p r o p o r t i o n of the treatment
p o p u l a t i o n , the t w o patients w i t h Cogan's s y n d r o m e a n d the one
w i t h c l i n i c a l a u t o i m m u n e i n n e r ear d i s e a s e s h o w e d t h e b e s t o v e r -
a l l r e s p o n s e t o I T c o r t i c o s t e r o i d i n j e c t i o n s . T w o o f t h e s e cases a r e
d e t a i l e d i n t h e p r e v i o u s case r e p o r t s .
O v e r a l l t h e r e h a v e b e e n n o serious l o n g - t e r m adverse effects
f r o m t r e a t m e n t . T h e r e w e r e n o cases o f t r e a t m e n t - i n d u c e d s e n s o r i -
n e u r a l h e a r i n g l o s s . I n a l l u n s u c c e s s f u l cases, t h e a u d i t o r y t h r e s h -
olds at least r e m a i n e d stable. No patients suffered f r o m persistent
vestibular dysfunction. Some complained of temporary vertigo at
the t i m e o f t h e i n j e c t i o n d u e t o t h e c a l o r i c effect o n t h e lateral s e m i -
c i r c u l a r canal. S o m e also c o m p l a i n e d of a b u r n i n g d i s c o m f o r t in
L.S. Parnes
t h e i r ear a n d s o m e t i m e s i n t h e i r t h r o a t . T h i s w a s g e n e r a l l y a s s o c i -
ated w i t h m e t h y l p r e d n i s o l o n e . T h e d i s c o m f o r t has lasted as l o n g
as 6 h o u r s after t r e a t m e n t , b u t the a d d i t i o n of l i d o c a i n e to t h e i n -
j e c t i o n s o l u t i o n h a s h e l p e d c o n s i d e r a b l y . T h e r e h a v e b e e n n o cases
of prolonged, lidocaine-induced vertigo. Three patients developed
otitis m e d i a d u r i n g t h e t r e a t m e n t course that necessitated a n alter-
a t i o n i n the t r e a t m e n t s c h e d u l e . A l l r e c o v e r e d after a p p r o p r i a t e a n -
tibiotic treatment. There have been no permanent tympanic m e m -
brane perforations.

Current Treatment Regimen


This treatment is offered to patients w i t h s u d d e n idiopathic sen-
s o r i n e u r a l h e a r i n g loss ( w h e n seen w i t h i n t h e first m o n t h after o n -
s e t ) , i m m u n e - r e l a t e d h e a r i n g l o s s a n d i n n e r ear s u r g e r y - r e l a t e d
h e a r i n g loss. For those patients c o n s e n t i n g t o t r e a t m e n t , w e d e s i g n
a schedule of t w i c e w e e k l y treatments d u r i n g a 3-week interval.
M e t h y l p r e d n i s o l o n e is the current preferred corticosteroid, but for
those w h o cannot tolerate the discomfort even w h e n a d d i n g the
l i d o c a i n e (there have been t w o patients), dexamethasone is a suit-
a b l e a l t e r n a t i v e . T h e i n j e c t i o n s o l u t i o n c o n s i s t s o f 0.9 m L o f t h e
standard intravenous methylprednisolone solution, 40 m g / m L
c o m b i n e d w i t h 0.1 m L o f 1 % l i d o c a i n e .
T h e treatments take place in the outpatient clinic u n d e r m i -
croscopic control in a similar fashion to the gentamicin injections.
In this setting, rigid endoscopy not only confirms the r o u n d w i n -
d o w l o c a t i o n a n d identifies a n y m u c o s a l adhesions, i t also a l l o w s
for the potential identification of a p e r i l y m p h fistula, w h i c h forms
part o f the differential diagnosis i n some patients w i t h s u d d e n hear-
i n g loss.
The first injection is done through the m y r i n g o t o m y using a
26-gg n e e d l e on a t u b e r c u l i n syringe, w i t h subsequent i n j e c t i o n s
proceeding through the Baxter tube. A u d i o m e t r i c testing, both dur-
i n g a n d after the t r e a t m e n t course, is i n d i v i d u a l i z e d for each p a -
tient d e p e n d i n g on their u n d e r l y i n g disorder, degree of h e a r i n g
loss, a n d subjective response to treatment. If the treatments y i e l d a
positive result, a further treatment schedule m a y be customized.

DISCUSSION
2 0
In our prior animal study, transtympanic corticosteroid adminis-
tration p r o d u c e d very h i g h drug levels in b o t h e n d o l y m p h a n d
p e r i l y m p h . Therefore, if the i n f l a m m a t o r y process is w i t h i n the
membranous or bony labyrinth, transtympanic delivery should be
e f f e c t i v e . If, h o w e v e r , t h e d i s e a s e p r o c e s s i s o u t s i d e t h e l a b y r i n t h ,
Intratympanic Pharmacotherapy 35

as occurs in cochlear or vestibular neuronitis, little benefit would


be expected from transtympanic administration. Systemic applica-
tion would be necessary in this situation.
It is not surprising that the hearing loss in the patient with Ram-
say Hunt syndrome continued to deteriorate during transtympanic
treatments, as this condition results from a viral infection of the
nerve itself. Conversely, Cogan's syndrome produces secondary ret-
rograde neuronal degeneration, with the primary pathologic fea-
25
tures localized to the inner e a r . Therefore, it is not surprising that
the two patients with Cogan's syndrome benefited greatly from
transtympanic corticosteroids.
The underlying pathology of sudden sensorineural deafness,
defined as 30 dB or more sensorineural hearing loss over at least
three contiguous audiometric frequencies occurring within 3 days
or less, remains controversial. A definitive cause can be found in
26
only 1 0 % to 1 5 % of c a s e s . Three pathophysiologic theories pre-
27
vail for the remaining "idiopathic" c a s e s . One ascribes to an in-
tralabyrinthine membrane rupture, whereas another postulates an
ischemic process. The third theory, which may have the most rel-
evance in IT corticosteroid treatment, is the viral theory.
The inflammation resulting from a viral infection of the inner
ear may be amenable to the effects of corticosteroids. However, as
previously stated, a viral infection localized to the eighth nerve
would resist this form of treatment. Schuknecht's temporal bone
study of eleven cases of sudden idiopathic hearing loss suggests
28
an underlying viral etiology in m o s t . The principal pathologic
changes involved the organ of Corti in six cases, a combination of
the organ of Corti and tectorial membrane in two, the tectorial
membrane only in two, and the cochlear neurons only in one. Not
only were the changes usually limited to the inner ear, they were
also very similar to those found in known cases of viral labyrinthi-
tis such as mumps, measles, and rubella.
Unquestionably, many cases of sudden deafness show sponta-
27
neous recovery without any treatment. The prognosis is best with
a mild hearing loss, an upward sloping audiogram, an absence of
26
vertigo, and when recovery begins within 2 weeks of o n s e t . Al-
though many treatments have been advocated for these cases of sud-
den hearing loss, none have been shown to be effective in a double-
blind placebo study. Unfortunately from a research standpoint, the
rarity of this disorder makes it virtually impossible for one center
to recruit enough patients for a meaningful controlled study.
I recruited only 14 sudden idiopathic hearing loss ears in 13
patients during a 2.5-year period of study. This included all pa-
L.S. Parnes
tients referred during this interval, excluding those who presented
more than 6 weeks from onset. Of the 12 ears that presented ini-
tially with a severe to profound loss, five recovered to normal hear-
ing thresholds, with one other restored to the serviceable range.
The progressive severe hearing loss in the patient who presented
initially with sudden bilateral deafness stabilized over time so that
he is now a successful bilateral hearing aid user. The small sample
size is, without a doubt, a shortcoming of this series. It is also pos-
sible that the ears in which hearing recovered may have done so
spontaneously without any therapy. However, given the severity of
the hearing losses, the chances of spontaneous improvement would
have been small.
More recently, some investigators have suggested an autoim-
mune etiology as an underlying cause of sudden deafness. Harris
29
and S h a r p studied 54 patients with rapidly progressive sensori-
neural hearing loss. Nineteen ( 3 5 % ) showed evidence of a specific
anticochlear antibody in their serum as compared with 7% of con-
trols. They used the Western blot analysis, which is currently the
best marker for immune inner ear disease.
3 0
Veldman et a l . also used the Western blot test to analyze the
sera from 71 patients with various types of hearing loss. Of the 15
patients with a rapidly progressive loss, 11 had a positive blot as-
say. However, patients from both the positive and negative assay
groups responded favorably to immunosuppressive therapy. Ste-
roid treatment alone was as effective as the combination of steroids
with cytostatic agents, with the overall response rate at 5 0 % . In
the sudden deafness group (n = 31), 6 5 % had a positive Western
blot assay. Steroid therapy was more effective than no therapy, re-
gardless of a positive or negative Western blot profile.
31
Shirwany et a l . assessed several effects of transtympanic in-
jection of dexamethasone in guinea pigs. These investigators dem-
onstrated an initial increase in cochlear blood flow that persisted
for at least 1 hour. They found no change in the auditory brain stem
responses. Also, there was no change in cochlear histology, but this
was an acute study that did not address the potential long-term ef-
fects of dexamethasone.
To date, there have been no long-term negative effects of IT cor-
ticosteroids in the patients followed up in this present study. Two
ears alone (case reports 1 and 2) have undergone a total of more
than 250 treatments during a 7-year interval. Both ears continue to
show normal auditory responses with no other evidence of adverse
effects.
Intratympanic Pharmacotherapy 37

T h e potential risks of systemic corticosteroids, in particular


the r i s k of avascular necrosis of the f e m o r a l h e a d , c a n n o t be over-
3 2
s t a t e d . I n t h a t f i r s t , t h e r e i s s t i l l n o h i g h l y s p e c i f i c m a r k e r t o se-
l e c t o u t t h o s e cases o f s u d d e n d e a f n e s s t h a t m i g h t h a v e a n u n d e r -
l y i n g i m m u n e - m e d i a t e d cause, a n d second, the efficacy of systemic
corticosteroids for s u d d e n deafness has n o t been substantiated in
clinical trials, r e c o m m e n d i n g a trial of IT methylprednisolone i n -
j e c t i o n s f o r a l l a c u t e cases o f s u d d e n i d i o p a t h i c d e a f n e s s t h e r e f o r e
seems reasonable. F u r t h e r m o r e , based on the c u r r e n t f i n d i n g s , IT
m e t h y l p r e d n i s o l o n e s h o u l d be the treatment of choice for verified
i m m u n e - m e d i a t e d i n n e r ear d i s e a s e .

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749.1993.
12. Kaasinen S, Pyykko I, Ishizaki H, et al: Effect of intratympanically ad-
ministered gentamicin on hearing and tinnitus in Meniere's disease.
Acta Otolaryngol (Stockh) 520:184-185,1995.
13. Rauch SD, Oas JG: Intratympanic gentamicin for treatment of intrac-
L.S. Parnés
table Meniere's disease: A preliminary report. Laryngoscope
107:49-55 1997.
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Intratympanic Pharmacotherapy 39

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CHAPTER3

Guidelines for Inpatient


Versus Outpatient
Adenotonsillectomy
in Children
Michael J. Cunningham, M.D.
Surgeon, Department of Otolaryngology, Massachusetts Eye and Ear
Infirmary; Associate Professor, Department of Otology and Laryngology
Harvard Medical School, Boston, Massachusetts

S o c i o e c o n o m i c a t t e m p t s to s t e m t h e r i s i n g cost of h e a l t h care
have r e s u l t e d in a significant e m p h a s i s on o u t p a t i e n t surgery.
Most otolaryngologists have readily accepted this trend, as evi-
denced by statistics s h o w i n g otolaryngology to be the t h i r d most
1
c o m m o n specialty using ambulatory surgical centers. The most
frequent otolaryngologic operations p e r f o r m e d on an outpatient ba-
sis are t h o s e t h a t i n v o l v e c h i l d r e n , s p e c i f i c a l l y b i l a t e r a l m y r i n g o t -
omy w i t h ventilation tube placement and adenotonsillar proce-
2
dures.
T h e substantial financial savings resulting f r o m the e l i m i n a t i o n
of o v e r n i g h t h o s p i t a l i z a t i o n has u n f o r t u n a t e l y led to insurance
c o m p a n y mandates that m a n y otolaryngologic procedures, i n c l u d -
i n g a d e n o t o n s i l l e c t o m y , b e p e r f o r m e d o n a n o u t p a t i e n t basis except
3
under extenuating circumstances. The appropriateness of outpa-
tient a d e n o t o n s i l l e c t o m y in specific patient p o p u l a t i o n s is debat-
able. Concerns also r e m a i n as to the p r o p e r d u r a t i o n of postopera-
tive m o n i t o r i n g to ensure patient safety relative to the p o t e n t i a l for
serious a n d even life-threatening postoperative complications.

PROCEDURE COMPLICATIONS
A n y discussion of inpatient vs. outpatient surgery needs to i n c l u d e
t h e r i s k s a s s o c i a t e d w i t h t h e p r o c e d u r e i t s e l f , a s w e l l a s t h o s e as-
sociated w i t h the patient p o p u l a t i o n on w h i c h it is performed. T h e
Advances in Otolaryngohgy-Head and Neck Surgery®, vol. 12
4 1
»1998, Mosby, Inc.
M.J. Cunningham

t e r m " o u t p a t i e n t " i n this chapter w i l l refer t o a n a m b u l a t o r y p r o -


cedure, whereas the term "inpatient" w i l l include both same day
a d m i t as w e l l as observation status patients. Relative to the proce-
dure, questions to be asked include the incidence and severity of
potential postoperative complications, the time frame during
w h i c h s u c h c o m p l i c a t i o n s occur, a n d w h a t factors associated w i t h
these c o m p l i c a t i o n s c o u l d be i d e n t i f i e d preoperatively to p r e d i c t
w h i c h patients s h o u l d be a d m i t t e d or observed for a longer t i m e
after surgery.
The most life-threatening complication of adenotonsillectomy
is hemorrhage. Postoperative hemorrhage is typically defined as
primary or immediate if it occurs w i t h i n the first 24 hours; it is
r e f e r r e d to as s e c o n d a r y or d e l a y e d if it occurs at a n y t i m e after
the f i r s t postoperative day. T h e i n c i d e n c e o f p r i m a r y h e m o r r h a g e
is of particular i m p o r t a n c e in the discussion of outpatient vs. i n -
patient adenotonsillectomy. Estimates of the incidence of p r i m a r y
postadenotonsillectomy hemorrhage in the pediatric population
range b e t w e e n 0 % a n d 5.4%, w i t h the m a j o r i t y o f studies d e m o n -
s t r a t i n g t h i s a s a v e r y i n f r e q u e n t p r o b l e m (see P r o c e d u r e C o m p l i -
4 1 9
cations i n Tables 1 , 2 , a n d 3 ) . " Differences i n i n c i d e n c e f i g u r e s
b e t w e e n s t u d i e s are d u e i n p a r t t o v a r i a t i o n s i n t h e d e f i n i t i o n o f
h e m o r r h a g e ; f o r e x a m p l e , f e w s t u d i e s d i s t i n g u i s h t h e g r a d e o r se-
verity of postoperative bleeding. One of the better grading systems
uses a f o u r - p o i n t n u m e r i c a l scale t h a t differentiates b e t w e e n no
b l e e d i n g , m i l d b l e e d i n g that stops spontaneously, moderate bleed-
i n g t h a t r e q u i r e s c a u t e r i z a t i o n , t o n s i l l a r fossa i n j e c t i o n o r i n t r a n a -
sal decongestant d r o p s , a n d severe b l e e d i n g necessitating place-
ment of posterior nasal packing and/or the patient's return to the
7
operating r o o m for hemostatic c o n t r o l .
T h e v o l u m e o f i n t r a o p e r a t i v e b l o o d loss i s also o f p o t e n t i a l i m -
portance, particularly in the young child. Total blood v o l u m e is
b e s t e s t i m a t e d a t 7.5 c c p e r 1 0 0 g o f b o d y w e i g h t . I n t r a o p e r a t i v e
b l o o d loss e x c e e d i n g 1 0 % o f t o t a l b l o o d v o l u m e has b e e n s i g n i f i -
2 0
cantly associated w i t h a c o m p l i c a t e d postoperative course.
Two of the more c o m m o n postoperative problems in children
a f t e r a d e n o t o n s i l l e c t o m y a r e e m e s i s a n d p o o r f l u i d i n t a k e . A cer-
t a i n degree of emesis is expected d u e to the anesthesia. Recurrent
or protracted emesis is, however, a significant concern because of
the risk of d e h y d r a t i o n . Estimates of the i n c i d e n c e of severe post-
adenotonsillectomy emesis in the pediatric p o p u l a t i o n range f r o m
0 . 7 % t o 7 . 5 % , w i t h r e p o r t e d d e h y d r a t i o n rates o f 0 . 3 % t o 1.9%
4 , 5 | 7 9 a 1 1 3 1 7
(see P r o c e d u r e C o m p l i c a t i o n s i n T a b l e s 1 , 2 , a n d 3 ) . ' ' - '
Perioperative protocols incorporating metaclopramide and newer
Guidelines for Adenotonsillectomy in Children 43

a n t i e m e t i c agents s u c h as o n d a n s e t r o n appear to be decreasing the


2 1 , 2 2
severity of this p r o b l e m .
T h e r o l e o f r e q u i r e d oral f l u i d i n t a k e after a d e n o t o n s i l l e c t o m y
is being reconsidered. Whereas offering s m a l l amounts of clear l i q -
uids to ensure that the c h i l d is able a n d w i l l i n g to d r i n k is appro-
priate, forcing fluids to establish r e s u m p t i o n of n o r m a l oral fluid
2 3
intake does n o t appear to be b e n e f i c i a l . T h e alternative a d m i n i s -
tration of adequate intraoperative a n d postoperative intravenous
fluids is crucial. Delayed oral intake necessitating prolonged intra-
v e n o u s h y d r a t i o n i s r e p o r t e d i n u p t o 9 % t o 1 6 % o f c h i l d r e n after
8 , 1 5
adenotonsillectomy S u c h i n t r a v e n o u s h y d r a t i o n s h o u l d re-
place cumulative f l u i d deficits related to the length of preopera-
tive N P O status, the v o l u m e of intraoperative b l o o d loss, a n d an-
ticipated deficits based on the d u r a t i o n of l i m i t e d postoperative
fluid intake. Some authors advocate that the v o l u m e of intravenous
fluids administered postoperatively should be equal to that child's
2 4 - h o u r r e q u i r e m e n t i n a n t i c i p a t i o n o f l i m i t e d o r a l f l u i d i n t a k e sec-
1 7
ondary to oropharyngeal discomfort. Intraoperative and postop-
erative intravenous h y d r a t i o n s h o u l d always be w i t h isotonic
2 4
solutions.
Another complication of particular significance in children u n -
dergoing adenotonsillectomy for obstructive airway indications is
postoperative respiratory compromise. This complication w i l l be
discussed in greater detail later in this chapter.

INPATIENT/OUTPATIENT ADENOTONSILLECTOMY STUDIES


N u m e r o u s studies have b e e n p u b l i s h e d assessing a d e n o t o n s i l -
4 9 2 0
l e c t o m y surgery f r o m a n i n p a t i e n t (Table i ) - - ; outpatient
1 0 1 5 1 6 1 9
(Table 2 ) , " a n d c o m p a r a t i v e i n p a t i e n t / o u t p a t i e n t (Table 3 ) "
p e r s p e c t i v e . T h e vast m a j o r i t y o f these s t u d i e s are r e t r o s p e c t i v e
case s e r i e s t h a t v a r y g r e a t l y i n t e r m s o f p a t i e n t d e m o g r a p h i c s a n d
p r o c e d u r e c o m p l i c a t i o n s assessed.
M a n y of the outpatient studies indicating ambulatory surgery
1 0 - 1 2
t o b e safe a n d e f f e c t i v e e i t h e r f a i l t o d e f i n e i n c l u s i o n c r i t e r i a
or specifically exclude certain patient populations from outpatient
1 3 1 5
s u r g e r y . " A m o n g t h o s e g r o u p s c o m m o n l y e x c l u d e d are c h i l d r e n
w i t h a i r w a y o b s t r u c t i o n i n d i c a t i o n s for surgery. T h i s observation
i s o f p a r t i c u l a r i m p o r t a n c e b e c a u s e u p p e r a i r w a y o b s t r u c t i o n sec-
ondary to l y m p h o i d hyperplasia is currently the most frequent i n -
2 5
dication for adenotonsillectomy in the pediatric p o p u l a t i o n .
Review of the comparative inpatient/outpatient studies reveals
that the preoperative application of outpatient exclusion criteria
TABLE 1.
Inpatient Adenotonsillectomy Studies

Study Outpatient Study Observations and/or


Author(s) Study Type Study Demographics Exclusion Criteria Procedure Complications Conclusions

Crysdale and Retrospective 7,707 TA Not applicable; • Primary hemorrhage 2 . 1 5 % Children younger than 4 yrs
Russell 4
case series 267 T all inpatients ( 7 6 % episodes within 6 hrs) had a lower relative frequency
1,435 A ( 8 7 % episodes within 9 hrs) of bleeding but a higher
Age < 1 7 yrs • Severe emesis 3 . 1 % incidence of fever, inadequate
oral intake, and respiratory
distress
Carithers, Retrospective 2 3 8 0 TA Not applicable; Primary hemorrhage 1.2% Using a definition of less than a
Gebhart and, case series 183 T all inpatients ( 4 1 % episodes within 4 hrs) 1 0 % risk of complications,
Williams 5
381 A ( 7 4 % episodes within 8 hrs) adenotonsillectomy patients
Age 1-23 yrs Severe emesis 7 . 5 % should be observed at least 8
hrs, and possibly 10 hrs,
postoperatively
Richmond, Retrospective 6 3 0 TA Not applicable; Primary hemorrhage 0 . 2 6 % 5 0 % of children with known
Wetmore case series 61 T all inpatients Emesis 5 5 % (severity not hematologic disorders had
and, B a r a n a k 6
93 A defined) postoperative bleeding
Age 9 m o s - 1 9 yrs Prolonged hospitalization 8 0 % o f children with
Airway obstruction 7 2 % or readmission due to poor postoperative airway
Recurrent infection 1 7 % oral intake 2 . 9 % complications had other
Both indications 1 4 % Major airway complications significant medical problems
1.3% 2 7 % of of children with Down
syndrome and other types of
congenital disorders had major
respiratory complications

Guida and Prospective 1,000 TA, T, A


7
Not applicable; 0-6 6-24 • Outpatient adenotonsillectomy
Mattucci case series Aee 2 - 3 5 vrs . , 1 1 ;„—u— „
1
congenital disorders had major
respiratory complications

Guida and Prospective 1,000 TA, T, A • Not applicable; 0-6 6-24 Outpatient adenotonsillectomy
7
Mattucci case series Age 2 - 3 5 yrs all inpatients hrs hrs is safe, provided a minimum of
( 8 0 % < 1 2 yrs) • Primary 6 hrs of postoperative
hemorrhage 0.7% 0.7% observation
• Severe
emesis 0.7% 0.7%
Berkowitz and Retrospective 1 9 0 TA, T • Not applicable; • Average blood loss 5 . 4 % Complications necessitating
Zalzal 20
case series Age <3 yrs all inpatients total blood volume prolonged hospital stay or
Airway obstruction 8 5 % • Loss of 1 0 % or more of readmission in 1 0 . 5 % patients;
Recurrent infection 1 5 % blood volume in 8% significant association with
greater than 1 0 % intraoperative
patients
blood volume loss
Rothschild, Retrospective 153 TA, T • Not applicable; • Primary hemorrhage 0% T h e most frequent
Catalano, case series Age 1-18 yrs all inpatients • Delayed oral intake 1 6 % postoperative problem was
8
and B i l l e r • Respiratory compromise delay in adequate oral
7% hydration. Airway problems
were less common, although of
greater concern
Two "at risk" subgroups
identified: patients S 3 yrs o f
age and patients with
obstruction
9
Tom et a l . Retrospective 223 TA, T • Not applicable; • Primary hemorrhage 0% Notably low incidence of
case series Age <3 yrs. all inpatients • Emesis 3 2 . 3 % (severity not postoperative bleeding and
Airway obstruction defined) dehydration
70.5% • Dehydration 1.8% High incidence of postoperative
Recurrent infection • Postoperative PICU care respiratory complications in
8.5% 7.6% this young patient population
Both indications 2 1 % • Management beyond
standard care 5 2 . 5 %

Abbreviations: TA, tonsillectomy and adenoidectomy; T, tonsillectomy; A, noidectomy.


TABLE 2.
Outpatient Adenotonsillectomy Studies
Duration of
Study Study Outpatient Exclusion Postoperative Procedure Study Observations
Author(s) Study Type Demographics Criteria Monitoring Complications and/or Conclusions

Maniglia, Retrospective 1,290 TA, T, A Not specified Not specified Primary Outpatient
Kushner and case series Age < 1 8 yrs hemorrhage 0 . 1 4 % adenotonsillectomy is
Cozzi 10
safe
Colclasure and Retrospective 3,340 TA, T, A Not specified 1.5-5.5 hrs Primary (tonsillar) Major complication
Graham 11
case series Age 1 - 3 9 yrs Mean 2.25 hrs hemorrhage 0 . 3 5 % rate of only 1.4%
(92% £ 1 6 Dehydration 0 . 3 % Less than 1% patients
yrs) required hospital
admission
Five of 7 patients who
bled were older than
16 yrs
Haberman, Retrospective 5 0 0 TA, T Not specified Not specified Primary Outpatient
Shattuck and case series Age range? hemorrhage 0 . 6 % adenotonsillectomy
Dion 12
(58% £ 1 2 Dehydration 0 . 6 % safe in a private
yrs) practice, community
hospital setting
Nicklaus, Retrospective 2 3 3 TA, T Age less than 3 yrs Average 2 hr Primary Short duration
Herzon, and case series Age £ 1 8 yrs Bleeding diathesis 16 mins hemorrhage 1.4% monitoring of
Steinle 13
Comorbid disease {e.\ Mean duration Severe emesis 2 . 5 % postadenotonsillectomy
asthma) 1 3 6 ± 48 mins patients is safe

Gabalski, Prospective 534 TA, T Obstructive sleep 5 - 6 hrs Complication rate Absence of
Steinle 13
• Comorbid disease (e.g., • Mean duration Severe emesis 2 . 5 % postadenotonsillectomy
asthma) 1 3 6 ± 48 mins patients is safe

Gabalski, Prospective 534 TA, T Obstructive sleep 5 - 6 hrs Complication rate Absence of
Mattucci, case series Age < 1 5 yrs apnea for first 4 complications in 5th
Setzen, et al. Morbid obesity postoperative hrs and 6th postoperative
Pickwickian syndrome not reported hrs. suggests that a 4-hr
Mucopolysaccharidoses Complication rate postadenotonsillectomy
Craniofacial anomaly for 5th and 6th monitoring period is
Congenital heart postoperative hrs safely appropriate
disease 0 . 1 9 % combined
Mental retardation
Known coagulopathy
Previous anesthesia
complication
Traveling distance
greater than 30 mins
from hospital
Poor parental care
situation
Mitchell, Retrospective 102 TA Obstructive sleep Minimum 4 hrs No reported Outpatient
Pereira, case series Age 1.5- 3 yrs apnea primary adenotonsillectomy is a
Friedman, Chronic illness hemorrhage safe procedure in
1 5
et a l . Previous anesthesia No reported children younger than
complications respiratory 3 yrs who are carefully
Bleeding diathesis complications selected
Living distance more 9 % hospital
than 1 hr from hospital admission rate
Unavailable personal from ambulatory
transport unit due to poor
No adult companion in oral intake
attendance

Abbreviations: TA, tonsillectomy and adenoidectomy; T, tonsillectomy; A, adenoidectomy


TABLE 3.
Inpatient/Outpatient Adenotonsillectomy Comparative Studies

Duration of
Study Study Outpatient Exclusion Postoperative Procedure Study Observations and/or
Author(s) Study Type Demographics Criteria Monitoring Complications Conclusions

Lee 1
Retrospective 3,240 TA Significant systemic Outpatients Primary 3 . 4 % children planned as
case series Age < 1 4 yrs disease 6 hrs hemorrhage 0 . 7 % outpatients admitted to
Planned inpatient Negative parental Inpatients hospital
32% attitude overnight 1 6 . 6 % children planned as
Planned Unfavorable inpatients discharged home
outpatient 6 8 % logistics same day
(distance/transport)
Intractable patient
(age/mentation)
Shott, Myer, Prospective 4 2 1 TA, T Age less than 3 yrs Outpatients Primary 1 1 % children planned a s
and C o t t o n 17
case series Age < 1 6 yrs Obstructive sleep 6 hrs hemorrhage 2 . 1 % outpatients admitted to
Planned inpatient apnea Inpatients Dehydration 1.9% hospital
22% Coexisting medical overnight
Planned problem
outpatient 7 8 % Living distance
over 1 hr from
hospital
Inadequate social
circumstances
Peritonsillar
abscess

Schloss, Tan, Retrospective 5 5 5 TA, T


Age younger than • Outpatients • Primary 1 6 . 2 % children r>l
n l f l n n p H
• Peritonsillar
abscess

Schloss, Tan, Retrospective 5 5 5 TA, T Age younger than Outpatients Primary 1 6 . 2 % children planned as
Schloss, case series Age not specified, 3 yrs not specified hemorrhage 5 . 4 % outpatients admitted to
1 8
et a l . but all children Living distance Inpatients ( 1 . 9 % required hospital
and adolescents more than 1 hr overnight operative Upper respiratory tract
Planned inpatient from hospital management) infection within 3 wks of
19% Obstructive sleep operation associated
Planned apnea significantly with
outpatient 8 1 % Coexisting medical postoperative hemorrhage
problem and aerodigestive tract
complications
Reiner, Retrospective 1,000 TA, T, A Associated cardiac Outpatients Primary Lower complication rates
Sawyer, case series Age 1-57 yrs or pulmonary 6 - 8 hrs hemorrhage in outpatient cases
Clark, et a l . 1
Planned disease Inpatients Inpatients 3 . 3 % attributed in part to
inpatients 4 0 % Central apnea or overnight Outpatients 1.2% selection of higher risk
Planned obstructive Poor oral intake patients for inpatient
outpatients 6 0 % episodes requiring Inpatients 4 . 8 % surgery
hospitalization Outpatients 1.2% No significant difference in
Abnormal complication rates between
coagulation indices operative diagnoses of
or bleeding history chronic infection and
Adverse upper airway obstruction
transportation, No significant difference in
distance from complication rates between
hospital inpatients and outpatients
Adverse social younger than 3 yrs of age,
situation regardless of procedure
performed or the surgical
indication

Abbreviations: TA, tonsillectomy and adenoidectomy; T, tonsillectomy; A, adenoidectomy.


50 M.J. Cunningham

limits ambulatory surgery to 6 0 % to 8 0 % of the patient popula-


16-19
tion originally a s s e s s e d . A postoperative outpatient-to-
inpatient conversion rate between 3% and 1 6 % is also docu-
1 6 - 1 8
mented. Alternatively, a certain percentage of patients initially
planned as inpatients do well enough to be discharged home as
outpatients. Many centers perform adenotonsillectomy surgery on
a so-called " 2 3 - h o u r " observation basis to account for this possi-
bility.
Many of these studies make recommendations as to the
appropriate duration of postoperative monitoring after adenoton-
5
sillectomy. Carithers et a l . attempted to define a subset of
adenotonsillectomy patients who could be discharged in fewer
than 24 hours. They established a postoperative complication rate
of 1 0 % as the ceiling below which discharge home would be
acceptable. They included bleeding, emesis, and dehydration
within their complication criteria, and estimated that adenoton-
sillectomy patients could be discharged safely after 8 to 10 hours
7
of postoperative observation. Guida and Mattucci documented
that the incidence of postadenotonsillectomy bleeding, emesis,
and fever changed very little between the first 6 hours and
subsequent 6 to 24 hours postoperatively, leading to a recom-
mended 6-hour postoperative monitoring stay. A total complica-
tion rate of only 0 . 1 9 % for the fifth and sixth postoperative hours
prompted Gabalski et a l . to suggest that a 4-hour postadenoton-
14

sillectomy monitoring period was safe and appropriate. Colcla-


11 13
sure and G r a h a m and Nicklaus et a l . have advocated periods
of postoperative monitoring as brief as 2 hours without significant
adverse sequelae.

IDENTIFICATION OF HIGH-RISK SUBGROUPS


Given the economic pressures pushing for the outpatient care of
adenotonsillectomy patients, otolaryngologists need to define more
accurately which groups of children require prolonged monitoring
and overnight monitoring in a hospital setting. The American
Academy of Otolaryngology—Head and Neck Surgery has made spe-
cific recommendations (Table 4) in terms of the identification of
such high-risk subgroups.

AGES YOUNGER THAN OR EQUAL TO 3 YEARS


An age of 3 years or younger has been shown to be significantly
associated with a higher risk of postadenotonsillectomy complica-
tions in many studies.
Guidelines for Adenotonsillectomy in Children 51

TABLE 4.
Tonsillectomy and Adenoidectomy Inpatient Guidelines:
Recommendations of the AAO-HNS Pediatric Otolaryngology
Committee (1996)*

Condition 1 Age 3 Years or Younger


Condition 2 Abnormal coagulation values with or without an
identified bleeding disorder in the patient or family
Condition 3 Evidence of obstructive sleep disorder or apnea due to
tonsil and/or adenoidal hypertrophy
Condition 4 Systemic disorders that put the patient at increased
preoperative cardiopulmonary, metabolic, or general
medical risk
Condition 5 Child with craniofacial and/or other airway
abnormalities including, but not limited to, syndromic
disorders such as Treacher Collins syndrome,
Crouzon's disease, Goldenhar's syndrome, Pierre Robin
anomalad, C.H.A.R.G.E. association, achondroplasia,
and most prominently, Down syndrome, as well as
isolated airway abnormalities such as choanal atresia
and laryngotracheal stenosis.
Condition 6 When the procedure is being done for acute
peritonsillar abscess
Condition 7 When extended travel time, weather conditions, and
home social conditions are not consistent with close
observation, cooperativeness, and ability to return to
the hospital quickly at the discretion of the attending
physician

Abbreviation: C.H.A.R.G.E., coloboma, heart disease, atresia choanae, retarded growth and
retarded development, genital hypoplasia, and ear anomalies or deafness.
'Reprinted with permission from the American A c a d e m y of Otolaryngology-Head and
Neck Surgery Bulletin, September 1 9 9 6 , pp. 1 3 - 1 5 .

4
Crysdale and Russell noted a higher incidence of postopera-
tive fever, inadequate oral intake, and respiratory distress in pa-
tients younger than age 4.
20
Berkowitz and Z a l z a l documented that a significant percent-
age ( 1 0 . 5 % ) of children younger than 3 years of age who undergo
adenotonsillectomy experience complications necessitating pro-
longation of their hospitalization beyond a planned single over-
52 M.J. Cunningham
n i g h t stay. T h e c o m p l i c a t i o n r a t e w a s p a r t i c u l a r l y h i g h i n t h o s e
c h i l d r e n w h o s e i n t r a o p e r a t i v e b l o o d loss e q u a l e d o r exceeded 1 0 %
of their total blood volume.
9
T o m e t a l . r e t r o s p e c t i v e l y r e v i e w e d 2 2 3 c h i l d r e n age 3 o r
younger w h o underwent adenotonsillectomy. The majority of this
patient p o p u l a t i o n u n d e r w e n t operative i n t e r v e n t i o n for obstruc-
tive airway indications alone (70.5%) or in association w i t h chronic
recurrent p h a r y n g o t o n s i l l i t i s episodes (21%). O n l y 8.5% of these
y o u n g c h i l d r e n h a d solely infectious i n d i c a t i o n s for surgery. A p -
proximately 8% of the children in this study required an intensive
care u n i t stay p o s t o p e r a t i v e l y , a n d m o r e t h a n 5 0 % n e e d e d s u p p l e -
mental therapy such as oxygen support, intravenous steroids, or i n -
travenous antiemetics. T h e incidence of postoperative emesis was
p a r t i c u l a r l y h i g h (32.5%), w i t h secondary i n t r a v e n o u s h y d r a t i o n re-
quirements to avoid dehydration in this young population.
8
R o t h s c h i l d , Catalano, a n d B i l l e r r e t r o s p e c t i v e l y r e v i e w e d 153
p a t i e n t s 1 8 y e a r s o f age o r y o u n g e r w h o u n d e r w e n t a d e n o t o n s i l -
lectomy. T w e n t y - t w o percent of the patients w e r e 3 years o l d or
younger; w i t h i n this subgroup, airway obstruction was the surgi-
cal i n d i c a t i o n for 8 1 % of these c h i l d r e n . T h e authors d o c u m e n t e d
a statistically significant difference in the time-to-oral-intake in pa-
t i e n t s y o u n g e r t h a n 4 y e a r s o f age c o m p a r e d t o t h o s e 4 y e a r s o f age
a n d o l d e r ; t h e y o u n g e r age g r o u p a l s o t o o k s i g n i f i c a n t l y l o n g e r t o
be discharged, p r i m a r i l y for this reason. A m o n g those c h i l d r e n u n -
dergoing adenotonsillectomy for relief of u p p e r a i r w a y obstruction,
7% experienced respiratory compromise in the immediate postop-
e r a t i v e p e r i o d . T h i s p e r c e n t a g e w a s h i g h e r ( 1 1 % ) i n t h e age g r o u p
y o u n g e r t h a n 4 years of age.
2 6
Gerber et a l . d o c u m e n t e d an even higher percentage (38%)
o f c h i l d r e n y o u n g e r t h a n 3 y e a r s o f age u n d e r g o i n g a d e n o t o n s i l -
lectomy for a i r w a y obstruction indications w h o developed postop-
erative respiratory c o m p r o m i s e . T h e relative risk of postoperative
respiratory c o m p r o m i s e w a s five t i m e s greater for patients y o u n g e r
t h a n 3 y e a r s o f age i n t h i s s t u d y .
N o t a l l s t u d i e s , h o w e v e r , h a v e i n d i c a t e d t h a t age a l o n e i s a s i g -
nificant risk factor for postadenotonsillectomy complications.
1 9
R e i n e r e t a l . f o u n d n o s i g n i f i c a n t d i f f e r e n c e i n c o m p l i c a t i o n rates
b e t w e e n i n p a t i e n t s a n d o u t p a t i e n t s y o u n g e r t h a n 3 years o f age,
regardless of the procedure p e r f o r m e d or the surgical i n d i c a t i o n .
1 5
M i t c h e l l et a l . , i n a r e v i e w o f 1 0 2 c h i l d r e n 3 y e a r s o f age o r
younger undergoing outpatient adenotonsillectomy, h a d a 10% ad-
m i s s i o n rate d u e to p o o r oral intake b u t r e p o r t e d no respiratory
compromise in this patient group postoperatively. They concluded
Guidelines for Adenotonsillectomy in Children 53

that ambulatory adenotonsillectomy was a safe procedure in


younger children who are carefully preoperatively selected. Nota-
bly, their operative group did not include children with airway ob-
struction.

OBSTRUCTIVE SLEEP DISORDER (OBSTRUCTIVE APNEA)


The majority of young children who undergo adenotonsillectomy
6, 9 2 0 , 25
do so for obstructive airway indications. ' Included in this
clinical spectrum are children with polysomnography-confirmed
obstructive sleep apnea as well as children with various combina-
tions of open mouth positioning, snoring, breathing pauses, rest-
less sleep, nocturnal enuresis, daytime somnolence, and morning
cephalgia suggestive of obstructive sleep disorder. Such children
are at risk for postoperative respiratory compromise for several rea-
sons. Surgical removal of hypertrophied tonsils and adenoid is as-
sociated with the postoperative development of tissue edema,
which itself causes oronasopharyngeal narrowing and increases
airway resistance. Anesthetic agents further promote upper airway
27
collapse by decreasing pharyngeal muscle dilator activity. Chil-
dren with chronic preoperative upper airway obstruction may ad-
ditionally have impaired central nervous system ventilatory re-
sponses to hypoxemia and hypercapnia, as well as adverse cardio-
28
pulmonary s e q u e l a . The latter may be identified preoperatively
by electrocardiographic evidence of right ventricular hypertrophy
29
and/or radiographic evidence of cardiomegaly. Postoperative pul-
monary edema has been reported after the operative relief of air-
30
way obstruction in such c h i l d r e n .
31
McColley et a l . documented a greater risk of postadeno-
tonsillectomy respiratory compromise in children with poly-
somnography-confirmed obstructive sleep apnea. In this study, the
severity of obstructive apnea was expressed as an obstructive event
index (OEI), reflective of the number of episodes of obstructive ap-
nea and obstructive hypoventilation per hour of sleep; an OEI
greater than 10 gave the highest probability of postoperative respi-
ratory compromise. Young age was also found to be a striking risk
factor, with the incidence of respiratory compromise in children
younger than 3 years of age being 5 2 % in this study. The combi-
nation of a high OEI and age below 3 years increased the risk of
postoperative respiratory compromise dramatically.
Obtaining a sleep study on every child with symptoms sugges-
tive of obstructive sleep disorder is neither practical nor cost ef-
fective. The performance of polysomnography is typically reserved
for those children in whom the diagnosis is in doubt, those whose
54 M.f. Cunningham

physical findings do not correlate w i t h the history of obstructed


b r e a t h i n g (e.g., t h e c h i l d w i t h o u t s i g n i f i c a n t a d e n o t o n s i l l a r h y p e r -
t r o p h y ) , those suspected of b e i n g at higher risk for postoperative
r e s p i r a t o r y c o m p r o m i s e (e.g., m o r b i d l y o b e s e c h i l d r e n ) , a n d t h o s e
c h i l d r e n w i t h o b s t r u c t i v e sleep d i s o r d e r w h o are p o o r s u r g i c a l r i s k s
b e c a u s e o f c o m p l i c a t i n g m e d i c a l f a c t o r s (e.g., b l e e d i n g d i a t h e s e s
or c o n g e n i t a l heart disease). P o l y s o m n o g r a p h y is also u s e d to dif-
ferentiate o b s t r u c t i v e f r o m central causes o f sleep apnea i n c h i l -
dren w i t h cerebral palsy, intractable seizures, a n d other n e u r o m u s -
cular disorders.
2 6
Gerber et a l . performed a prospective study to determine
w h i c h preoperative clinical criteria based on parental history c o u l d
accurately i d e n t i f y those pediatric patients at risk for postopera-
t i v e r e s p i r a t o r y c o m p r o m i s e after a d e n o t o n s i l l e c t o m y . T h e y s t u d -
i e d 2 9 2 c h i l d r e n a n d a d o l e s c e n t s b e t w e e n t h e ages o f 1 7 m o n t h s
a n d 19 years. F o r t y - f o u r of these 292 patients e x p e r i e n c e d postop-
erative r e s p i r a t o r y c o m p r o m i s e d e f i n e d as at least one of t h e f o l -
l o w i n g o c c u r r i n g m o r e t h a n 2 h o u r s a f t e r s u r g e r y : (1) a n o x y g e n
s a t u r a t i o n l e v e l l e s s t h a n 9 0 % f o r a t l e a s t 1 0 s e c o n d s ; (2) a n o b -
s t r u c t i v e b r e a t h i n g p a t t e r n ; o r (3) r e s p i r a t o r y d i s t r e s s r e q u i r i n g i n -
tervention. A l l 44 of these patients w e r e a d m i t t e d for overnight ob-
servation, a n d 20 c h i l d r e n required hospitalization for longer than
2 days. Preoperative clinical criteria associated w i t h an increased
risk of postoperative respiratory compromise i n c l u d e d a history of
restless sleep p a t t e r n , n o c t u r n a l d i f f i c u l t y i n b r e a t h i n g , o r l o u d
s n o r i n g w i t h b r e a t h h o l d i n g o f 1 0 s e c o n d s o r l o n g e r . P a t i e n t age
y o u n g e r t h a n 3 years a n d c o n c o m i t a n t significant m e d i c a l c o n d i -
tions w e r e also s h o w n t o correlate clearly w i t h a n increased r i s k
of postoperative respiratory compromise. The authors concluded
that a l t h o u g h sleep p o l y s o m n o g r a p h y w i l l c o n t i n u e t o b e t h e best
predictor of postoperative airway complications, an accurate pa-
r e n t a l h i s t o r y c a n also assist i n t h e i d e n t i f i c a t i o n o f those c h i l d r e n
w h o may require prolonged overnight observation.
3 2
Price, H a w k i n s , a n d K a h l s t r o m retrospectively r e v i e w e d 160
c h i l d r e n b e t w e e n 8 m o n t h s a n d 1 3 y e a r s o f age w h o u n d e r w e n t
adenotonsillectomy for obstructive airway indications. O n e h u n -
d r e d fifteen of these patients were discharged on the first postop-
erative day; 45 patients r e m a i n e d in the hospital for periods rang-
i n g f r o m 2 to 20 days. T h i r t y of these 45 patients e x p e r i e n c e d re-
spiratory c o m p l i c a t i o n s postoperatively. T h e m a j o r i t y of these
children had significant preoperative obstructive airway symp-
t o m s ; those w i t h o b s t r u c t i v e a i r w a y manifestations severe e n o u g h
Guidelines for Adenotonsillectomy in Children 55

to warrant urgent adenotonsillectomy were at particular risk for


postoperative difficulties.
33
Biavati, Manning, and P h i l l i p s retrospectively assessed, in
historical cohort fashion, 355 children and adolescents younger
than 18 years of age who underwent adenotonsillectomy for ob-
structed breathing during sleep (OBS). They defined OBS as a his-
tory of increasing snoring punctuated by apneic or hypopneic epi-
sodes with arousals. Using stepwise logistic regression analysis,
five associated medical conditions were identified as important
predictors of a complicated postoperative course: cerebral palsy,
seizures, age younger than or equal to 3 years, congenital heart dis-
ease, and prematurity. Complications included airway obstruction,
apnea with oxygen desaturations less than 9 0 % , and interventions
such as the administration of supplemental oxygen, placement of
a nasopharyngeal airway, or endotracheal intubation. Their conclu-
sion was that children with one or more of these preoperative risk
factors should be considered candidates for postoperative inpatient
observation.

CONCOMITANT SYSTEMIC DISORDERS


An additional underlying medical condition of insufficient sever-
ity to warrant inpatient status may, when combined with the other
aspects of postadenotonsillectomy recovery, argue in behalf of an
6
overnight stay. Richmond et a l . observed that 8 0 % of postadeno-
tonsillectomy airway complications occurred in children with
2 8
other systemic medical problems. Gerber et a l . found that the risk
of postoperative airway compromise was five times greater, for ex-
ample, in patients with underlying neuromuscular disorders. Bia-
33
vatie et a l . also found an increased risk of postoperative respira-
tory compromise in children with the following complicating
medical conditions: cerebral palsy, seizure disorder, prematurity,
34
and congenital heart disease. McGowan et a l . also noted an in-
creased risk of postadenotonsillectomy complications in children
with a history of prematurity, particularly those who required prior
intubation or who had bronchopulmoary dysplasia.

CONCOMITANT AIRWAY PROBLEMS


Children with craniofacial disorders characterized by reduced ana-
tomical dimensions of the upper airway such as mandibular hyp-
oplasia, Treacher Collins syndrome, Crouzon's disease, Golden-
har's syndrome, Pierre Robin anomalad, C.H.A.R.G.E. (coloboma,
heart disease, atresia choanae, retarded growth, genital hypoplasia,
56 M.J. Cunningham

a n d ear a n o m a l i e s ) a s s o c i a t i o n , a c h o n d r o p l a s i a , a n d D o w n s y n -
d r o m e are p r o n e t o a i r w a y o b s t r u c t i o n f r o m a d e n o t o n s i l l a r h y p e r -
6
trophy. In such children, even physiologically normal amounts of
oropharyngeal a n d nasopharyngeal l y m p h o i d tissue m a y result in
a i r w a y c o m p r o m i s e . S u c h c h i l d r e n are s i m i l a r l y a t h i g h e r r i s k for
2 6
postoperative a i r w a y c o m p r o m i s e . Gerber et a l . d o c u m e n t e d the
risk of postoperative respiratory c o m p r o m i s e to be nearly eight
times greater if the patient h a d an u n d e r l y i n g c h r o m o s o m a l
3 1
anomaly. McColley et a l . likewise observed an increased risk of
severe obstructive apnea i n c h i l d r e n w i t h craniofacial s y n d r o m e s ,
particularly those associated w i t h midface hypoplasia.
2 6
I n t h e r e a l m o f associated a i r w a y p r o b l e m s , Gerber e t a l . also
established that postoperative respiratory c o m p r o m i s e was three
times more likely to develop in patients w h o had an upper respi-
ratory tract i n f e c t i o n w i t h i n 4 weeks of their adenotonsillectomy.
This increased risk of postadenotonsillectomy complications in
c h i l d r e n w i t h recent respiratory tract i n f e c t i o n has been d o c u -
1 8
m e n t e d by other authors as w e l l , strongly suggesting that a his-
tory of recent respiratory tract illness warrants overnight observa-
t i o n , if not delay of surgery.

CONCOMITANT BLEEDING DISORDER


I n the m a j o r i t y o f studies assessing p o s t a d e n o t o n s i l l e c t o m y c o m -
plications in children, the risk of bleeding in otherwise healthy
children in the immediate postoperative period is quite m i n i m a l .
T h e use o f a s p i r i n a n d n o n s t e r o i d a l a n t i i n f l a m m a t o r y agents
s h o u l d o b v i o u s l y be a v o i d e d for at least 2 w e e k s before surgery.
T h e risk o f postoperative h e m o r r h a g e is, h o w e v e r , s i g n i f i c a n t l y i n -
creased if there is an i d e n t i f i e d b l e e d i n g disorder in the patient or
family. In one retrospective review of pediatric adenotonsillectomy
patients, 5 0 % of the c h i l d r e n w i t h k n o w n hematologic disorders
6
experienced postoperative bleeding. Specific management proto-
cols are a v a i l a b l e for p a t i e n t s w i t h c o a g u l o p a t h i e s s u c h a s v o n W i l -
3 5 3 6 3 7
lebrand's disease a n d h e m o p h i l i a ' as w e l l as for patients w i t h
3 6
various hemoglobinopathies such as sickle cell disease. A l l such
protocols require inpatient management.

W H E N THE PROCEDURE IS BEING DONE FOR ACUTE


PERITONSILLAR ABSCESS
T h e indications for the performance of acute (quinsy) tonsillectomy
i n t h e t r e a t m e n t o f p e r i t o n s i l l a r abscess a r e w e l l o u t l i n e d i n t h e
3 0 4 1
l i t e r a t u r e . " T h e average n u m b e r of h o s p i t a l days for patients u n -
dergoing quinsy tonsillectomy in the adult population is approxi-
Guidelines for Adenotonsillectomy in Children 57
4 2
m a t e l y 3 d a y s . T h e d r a i n a g e o f p e r i t o n s i l l a r abscess b y i m m e d i -
ate t o n s i l l e c t o m y i n y o u n g c h i l d r e n appears t o b e s i m i l a r l y p r o b -
4 3
lematic, w i t h an average h o s p i t a l stay of 72 h o u r s .

CLINICAL INTANGIBLES
T h e d i s t a n c e o f t h e f a m i l y ' s h o m e f r o m t h e site o f s u r g i c a l care,
extended travel time due to weather conditions or transportation
issues, a n d i n a d e q u a t e h o m e s u p e r v i s i o n m a y create a s i t u a t i o n
that is not consistent w i t h appropriate h o m e m o n i t o r i n g and the
ability to return the c h i l d to the hospital quickly. Parental c o m p l i -
a n c e , l a n g u a g e i s s u e s , a n d a c c e s s t o a c a r o r t e l e p h o n e are a l l i m -
p o r t a n t variables that i n f l u e n c e the safety o f h o m e discharge a n d
warrant consideration of overnight observation.

CONCLUSION
T h e d e c i s i o n t o p e r f o r m o u t p a t i e n t vs. i n p a t i e n t adenotonsillec-
t o m y d e p e n d s o n t h e s u r g i c a l i n d i c a t i o n ( s ) , t h e age a n d m e d i c a l
background of the patient, the family's social situation, and the pro-
fessional j u d g e m e n t of the operating surgeon. In general, it appears
t h a t o t h e r w i s e h e a l t h y c h i l d r e n 3 y e a r s o f age a n d o l d e r c a n s a f e l y
undergo adenotonsillectomy for either infectious or obstructive i n -
dications on an outpatient, a m b u l a t o r y basis. P r o l o n g e d i n p a t i e n t
o b s e r v a t i o n s h o u l d be c o n s i d e r e d for c h i l d r e n y o u n g e r t h a n 3 years
o f age, e s p e c i a l l y t h o s e u n d e r g o i n g a d e n o t o n s i l l e c t o m y f o r treat-
m e n t o f o b s t r u c t i v e s l e e p d i s o r d e r , a n d f o r p a t i e n t s o f a n y age w h o
are i d e n t i f i e d a s h a v i n g a s i g n i f i c a n t r i s k f a c t o r f o r a c o m p l i c a t e d
p o s t o p e r a t i v e c o u r s e . W h e n m u l t i p l e r i s k f a c t o r s are p r e s e n t , o v e r -
night hospitalization is required, and observation in an intensive
care u n i t o r s i m i l a r m o n i t o r e d setting m a y a c t u a l l y b e the m o s t p r u -
dent postoperative course.

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29. Goldenberg JD, Portugal LG, Wenig BL, et al. Negative-pressure pul-
monary edema in the otolaryngology patient. Otolaryngol Head Neck
Surg 117:62-66, 1997.
30. Feinberg AN, Shabino CL. Acute pulmonary edema complicating ton-
sillectomy and adenoidectomy. Pediatrics 75:112-114, 1985.
31. McColley SA, April MM, Carroll JL, et al. Respiratory compromise af-
ter adenotonsillectomy in children with obstructive sleep apnea. Arch
Otolaryngol Head Neck Surg 118:940-943, 1992.
32. Price SD, Hawkins DB, Kahlstrom EJ. Tonsil and adenoid surgery for
airway obstruction: Perioperative respiratory morbidity. Ent J 72:526-
531, 1993.
33. Biavati MJ, Manning SC, Phillips DL. Predictive factors for respira-
tory complications after tonsillectomy and adenoidectomy in chil-
dren. Arch Otolaryngol Head Neck Surg 123:517-521, 1997.
34. McGowan FX, Kenna MA, Fleming JA, et al. Adenotonsillectomy for
upper airway obstruction carries increased risk in children with a his-
tory of prematurity. Pediatr Pulmonol 13:222-226, 1992.
35. Gumprecht TF, Cichon JV. Otolaryngology and von Willebrand's dis-
ease. Arch Otolaryngol Head Neck Surg 107:481-493, 1981.
36. Lekas MD, DiBenodetto J, Smith PS, et al. Surgery on patients with
hemostatic disorders. Laryngoscope 92:873-877, 1982.
37. Scott TA, Jackler RK, Koerper MA. Management of hemophilia in oto-
laryngologic surgery: A contemporary protocol. Arch Otolaryngol
Head Neck Surg 114:1445-1448, 1988.
38. Halvorson DJ, McKie V, McKie K, et al. Sickle cell disease and tonsil-
lectomy: Preoperative management and postoperative complications.
Arch Otolaryngol Head Neck Surg 123:689-692, 1997.
39. Herzon FS. Peritonsillar abscess: Incidence, current management prac-
tices, and a proposal for treatment guidelines. Laryngoscope 1 0 5 : S l -
17, 1995.
40. Wolf M, Kronenberg J, Kessler A, et al. Peritonsillar abscess in chil-
dren and its indication for tonsillectomy. Int f Pediatr Otorhinolaryn-
gol 16:113-117, 1988.
41. Wolf M, Erven-Chen I, Talmi YP, et al. The indication for tonsillec-
tomy in children following peritonsillar abscess. Int J Pediatr Otorhi-
nolaryngol 31:43-46, 1995.
60 M.J. Cunningham
42. Lockhart R, Parker GS, Tami TA. Role of quinsy tonsillectomy and the
management of peritonsillar abscess. Ann Otol Rhinol Laryngol
100:569-571, 1991.
43. Friedman NR, Mitchell RB, Pereira KD, et al. Peritonsillar abscess in
early childhood: Presentation and management. Arch Otolaryngol
Head Neck Surg 123:630-632, 1997.
CHAPTER 4
Laser Surgery in the
Management of Carcinoma
of the Supraglottic Larynx
and Hypopharynx
Heinrich H. Rudert, M.D.
Professor of Otolaryngology and Chairman, Department of
Otorhinolaryngology, Head and Neck Surgery, University of Kiel, Kiel,
Germany

S upraglottic partial laryngectomy was first described by Alonso

3
1
in 1 9 4 7 and later modified by Leroux Robert, Sanchez Ro-
4 5 r>
driguez, B o c c a , Banfai in Europe, and Ogura and S o m in the
2

United States. It is an accepted method for the surgical treatment


of T to T supraglottic carcinomas and selected T supraglottic car-
a 2 3

cinomas. The risk for a local recurrence is low if the cases are care-
fully chosen. The oncologic outcome depends much more on the
metastases to local lymph nodes and to distant sites and on the
8, 9
occurrence of secondary malignancies.
Despite the good oncologic results, the acceptance of open su-
praglottic partial resections is distinctly limited because of its post-
operative morbidity. The high tendency of aspiration combined
with swallowing difficulties must be mentioned. A permanent tra-
cheostomy or a percutaneous gastric feeding tube is often required.
10 11
In many cases, a secondary laryngectomy cannot be a v o i d e d . '
The nondecannulation rate after open supraglottic partial resec-
tions amounts to about 2 5 % in supraglottic tumors and to about
1 2
5 0 % in tongue-base tumors according to Suarez et a l . The
12
completion laryngectomy rate rises after the age of 65 y e a r s . Af-
ter additional radiation therapy, the morbidity rate is higher than
10
after surgery a l o n e .
Prior to the introduction of the C O laser, endoscopic transoral
z
13-15
resections of supraglottic tumors were only done s p o r a d i c a l l y ,
Advances in Otolaryngology-Head and Neck Surgery®, vol. 12 „ .
e
1 9 9 8 , Mosby, Inc.
H.H. Rudert

because the appropriate instruments for the removal of larger


pieces of the larynx were not available. This changed after the
16
introduction by Jako and Strong of the C 0 laser. In 1978,
2

Vaughan was the first to resect supraglottic carcinomas with the


17 1 8 , 1 9
C 0 laser. In the following period, Davis et a l . ,
2 Zeitels
2 0 2 2 2 3 2 4 25 26
et a l . , " Steiner, ' Eckel and Thumfart, Rudert, and
2 7 - 2 9
Rudert and W e r n e r reported their experiences with this
method. Despite these reports about successful endoscopic resec-
tions, transoral laser surgical resections of supraglottic carcino-
mas with the C 0 laser have not yet found a permanent place
2

among surgical partial resections. One could get the impression


that the history of very gradual acceptance of open supraglottic
partial resections is repeating itself with transoral resections.
Good experiences in the endoscopic palliative laser debulking
of extensive supraglottic carcinomas were the reason for us to ex-
pand the transoral techniques. We went ahead step by step. First,
we performed transoral laser surgical debulking of large tumors
blocking the airways, to avoid tracheotomy. In these cases, laryn-
gectomy could then be performed as an elective procedure and
without impairment by the tracheostoma. We observed that post-
operative functional problems occurred only rarely, even after ex-
tensive tumor reduction with the C 0 laser.
2

After these good experiences, we used laser surgical treatments


in patients with inoperable cervical lymph node metastases and in
patients who refused a laryngectomy. Because many of these pa-
tients had no recurrence in the area of the primary tumor, we be-
gan to transorally resect suitable supraglottic carcinomas with a
curative intention. Treatment of the regional lymph nodes was usu-
ally carried out by bilateral neck dissection, even on a No-neck,
unless the general condition of the patient did not permit a pro-
longed operation.
Repeatedly we were surprised by the low postoperative mor-
bidity. Temporary aspiration and swallowing difficulties arose
when an arytenoid cartilage had to be removed, or when the su-
praglottic portion was removed down to the anterior commissure.
Because of these good functional results, we no longer observe an
age limit. Also, more patients with cardiopulmonary and liver dis-
eases are being treated by laser surgery than before, when the
method of choice was the external approach. Because of this, our
statistics show a relatively high number of patients who died
during follow-up from causes unrelated to the tumor. The advan-
tage for them was that they no longer suffered from their larynx
impairments.
Laser Surgery for Supraglottic Larynx and Hypopharynx Carcinoma 63

Our next step was to apply these resection techniques to carci-


22, 30
noma of the hypopharynx. In the beginning, carcinomas of the
pharyngeal sides of the aryepiglottic fold and the posterior and lat-
eral walls of the pharynx were resected. Among these patients, too,
the low rate of postoperative morbidity was remarkable. The next-
to-last step was to treat cancers of the piriform sinus with laser sur-
gery. As with the resections of cancers in the other locations of the
hypopharynx, the good functional results were surprising. The pa-
tients did not, as a rule, have to undergo tracheostomy because
there was no tendency toward aspiration. This low rate of morbid-
ity and the lack, in most cases, of surgical alternatives to a laryngec-
tomy urges us to give top priority to transoral laser surgical partial
hypopharyngeal resections with the goal of preserving the larynx.
The prerequisite, of course, is the proof that the oncologic results
are comparable to those of classic methods of treatment.

ANATOMICAL PRELIMINARY REMARKS AND CONFORMITY


OF TUMOR GROWTH
The study of the anatomy of the larynx shows that supraglottic tu-
mors are more suitable for a transoral laser surgical operation than
tumors at the level of the vocal folds. The suprahyoid epiglottis is
positioned completely above the laryngeal skeleton and can be ap-
proached from all sides through a supraglottiscope for endoscopic
laser resection. The infrahyoid epiglottis also is not completely
confined by the laryngeal skeleton. In tumors of this subsite of the
supraglottis, it is important to include the pre-epiglottic space in
the resection. This is facilitated by the existence of a pseudocap-
3 1 , 3 2
sule, which tumors push into the pre-epiglottic s p a c e . Tumors
of the aryepiglottical folds and the arytenoid region can also be
transorally removed if they have not invaded the paraglottic space.
The same is true for tumors of the false cord.
The theoretical foundation for supraglottic partial resections is
4
based on the clinical observations of B o c e a , which are supported
33
by the histologic observations of K i r c h n e r , that some sort of
growth barrier exists between the supraglottic and the glottic space,
but the morphologic substrate has never been proved. Their as-
sumption has, however, heavily influenced the acceptance of the
34
supraglottic partial resections. Recent studies by Sato et a l . and
35 36
Martina R e i d e n b a c h ' of the pre-epiglottic and the paraglottic
space have shown that a continuous separation of these spaces does
not exist and that tumors that have invaded one of these spaces can
also grow into the other one. This is especially true for the lateral
64 H.H. Rudert

appendages of the pre-epiglottic or the periepiglottic space, whose


border to the paraglottic space along the thyreoglottic ligament
shows gaps. Also, a separation of the lymphatic drainage of the su-
praglottis and the glottis, assumed on the grounds of injection ex-
37
periments by Pressman et a l . , could not be verified by new experi-
38
ments by Werner et a l . After renewed examination of Tucker's
39
collection and considering the works of Olofsson and Nostrand
40 41
and of McDonald et a l . , Weinstein et a l . suspect that the prob-
ability of an invasion of supraglottic carcinomas into the glottic
level is between 2 0 % and 5 0 % , if all tumor stages are taken as a ba-
41
sis. Weinstein et a l . discovered that involvement of the vocal
folds could always be observed when the ventricular side of the
false cord was affected or if there was an impairment of the mobil-
ity of a vocal fold. In the material examined by the authors, the
growth of the supraglottic tumors occurred in most cases through
the paraglottic space. The growth occurred on the surface of the vo-
cal fold in continuity only in tumors of Morgagni's ventricle. It can
be concluded from these observations that the decision for a supra-
glottic partial resection must be made very critically with regard to
surface growth and the mobility of the vocal folds. This is also valid
for extralaryngeal and endolaryngeal techniques.
The transoral laser resection of hypopharyngeal carcinoma is,
like those of the supraglottic carcinomas, not hampered by the la-
ryngeal skeleton, if one disregards postcricoid carcinoma and the
carcinoma of the medial wall of the piriform sinus. Therefore, even
extensive tumors of the posterior wall of the hypopharynx reach-
ing into the oropharynx can be resected, as long as these have not
invaded the prevertebral longitudinal ligament. In the area of the
lateral walls of the hypopharynx, the tube of the pharyngeal con-
strictor muscles often forms the border of the tumor growth. For
this reason, tumors with a relatively great linear expansion but with
a shallow depth of penetration can be transorally resected. Tumors
of the walls of the piriform sinus can only be resected if they have
not grown into the thyroid cartilage or the cricoid cartilage. It can
also be observed that the paraglottic space borders posterolaterally
on the medial wall of the piriform sinus, so that tumors of the me-
dial piriform sinus growing infiltratively can spread into the pos-
terior part of the paraglottic space. The surface infiltration of an
arytenoid region does not pose a contraindication to laser surgical
resection, although the resection must then include the arytenoid
cartilage. Postcricoid tumors are not suitable for laser surgical re-
section because they are difficult to reach endoscopically and have
generally invaded the cricoid cartilage. The scar formation, which
Laser Surgery for Supraglottic Larynx and Hypopharynx Carcinoma 65

leads to stenosis, causes swallowing difficulties and aspirations.


The method of choice for these tumors, often growing circularly,
is a laryngectomy with successive reconstruction by a jejunum free-
tissue transfer.

ANESTHESIA
The operations are always performed under orotracheal intubation.
Tubeless operations under jet ventilation or with the apneic tech-
nique are not helpful since the tracheal tubes remain outside the
operational area anyway. For beginners, the use of so-called laser-
resistant endotracheal tubes is recommended. They are, however,
42
very costly and not absolutely safe from the risk of tube fires. We
use normal thin-walled polyvinyl tubes with the smallest possible
diameter, the cuff of which is filled with Ringer's solution. The
tubes are protected with moist neurosurgical cottonoid. It is impor-
4 2
tant that the O content of the gas mixture does not exceed 4 0 % .
z

In 19 years, we have not seen a single tube fire.


After extensive resections, we observe the patients for 1 day in
intensive care, because there have been isolated incidences of post-
operative bleeding, especially from the tongue base. Respiratory
problems with edema of the mucosa only occurred occasionally if
a bilateral neck dissection was performed. A temporary tracheos-
tomy was performed on these patients.

INSTRUMENTS AND LASER SYSTEMS


For operations on the supraglottis, the closed laryngoscopes
according to Kleinsasser, Dedo, Lindholm, and others are not suit-
able. Endoscopes are needed that can be applied like an anesthe-
siologist's intubate spatula into the valleculae and that will, in ad-
dition, keep the intubation tube back and the tongue to one side.
Bivalved laryngoscopes are suitable for this. We have developed a
43
supraglottiscope out of a spreadable laryngoscope of Weerda, in
which the side plates of the two spatulas are placed just so that
the edges of the tongue, even in the spread position, cannot come
into the field of vision and operation (Fig 1A, I B ) . The bivalved
44 45
endoscope, developed by S t e i n e r and modified by Z e i t e l s , is
also suitable. The endoscopes are provided with suction tubes to
evacuate the laser smoke.
Suction tubes and small forceps, which are suitable for
monopolar coagulation, are important instruments. They are elec-
trically insulated in the area of the shaft. The shafts of the forceps,
according to Kleinsasser, had suction channels added that reached
66 H.H. Rudert

FIGURE 1.
A, bivalved supraglottiscope (STORZ Comp., Tuttlingen); B, view of the supra-
glottic larynx exposed with the supraglottiscope.

to the mouth of the instruments (Fig 2), because the suction tubes
of the laryngoscopes do not have adequate suction power because
46
of their small diameter and the great distance to the o b j e c t .
The majority of the C 0 lasers on the market are suitable for
2

laser surgery of the larynx, if they can be coupled to an operating


microscope with a focus of 4 0 0 mm. Lasers with an output of 25
W are sufficient. We use the continuous wave (cw) mode almost
exclusively, with which one can cut and dissect as though with a
scalpel, with low energy use ( 1 - 2 W). We recommend using a mod-
ern micromanipulator, which generates a spot size of 0.25 mm at
4 0 0 mm. The C 0 laser is used exclusively as a cutting instrument,
2

never for vaporization. With modern micromanipulators, one can


2
reach a power density of 2 0 0 0 to 4 0 0 0 watts/cm at only 1-2 W.
This produces a vastly smoother and finer cut than conventional
micromanipulators, which need 1 0 - 1 3 W for the same power den-
sity. T h e irreversibly damaged zone of coagulation amounts to only
0.5 mm. The pathologist can thus judge the resection margins as
well as after resection with a scalpel.
Laser Surgery for Supraglottic Larynx and Hypopharynx Carcinoma 67

FIGURE 2.
Instruments for laser surgery.
68 H.H. Rudert

One great advantage of the C O laser is that the capillary blood


z

vessels remain closed during the incision through the tissue. Under
the microscope, the targeted hemostasis allows good recognition of
the border between healthy and tumorous tissue on the surface of
17
the incision. As early as 1 9 7 8 , Vaughan used these characteristics
to undertake a staging of advanced tumors. It is our opinion that,
contrary to conventional oncosurgical rules, even tumors that can-
not be endoscopically removed in one piece can be divided and re-
sected in two or three pieces, due to the sealing of the capillary
blood vessels and lymphatic vessels. Of course, the final margin of
the resected piece of the remaining laryngeal stump must be free of
tumor cells. This can best be achieved by taking edge slices from
the remaining laryngeal stump after the resection of the tumorous
area of the supraglottis and examining them histologically. If it is
not possible to obtain adequate tumor-free margins, the operation
should be stopped. The great advantage of transoral laser surgery is
that the option for all other methods of treatment remains open.

RESECTION TECHNIQUES
Laser surgical resection techniques and open supraglottic partial
resections both represent operation methods, which must be
learned and practiced systematically. This can best be done on
larynges of cadavers.

RESECTION OF TUMORS OF THE SUPRAHYOID EPIGLOTTIS


Small carcinomas of the suprahyoid epiglottis, especially of the
epiglottis edge, are removed in one piece after they have been ex-
posed by the laryngoscope (excisional biopsy). One grasps the epi-
glottis with alligator forceps and cuts around the tumor with a se-
curity margin of about 1 cm (Fig 3). The healthy part of the epi-
glottis remains. A tracheostomy or the insertion of a feeding tube
is rarely necessary because the patients have no problems with as-
piration or swallowing after the transoral resection.
The resection of more extensive tumors is greatly facilitated by
splitting the epiglottis (Figs 4 and 5). The first vertical incision di-
vides the epiglottis in the midline or, depending on the location of
the tumor, paramedially. The incision reaches into the valleculae.
Due to the hemostasis generated by the C 0 laser beam, one can,
2

under the microscope, easily recognize on the surface of the cut


when healthy tissue has been reached again. The next incision
slices bilaterally through the healthy tissue into the valleculae un-
til the pharyngoepiglottic fold has been reached. After the separa-
tion, the next incision divides the aryepiglottic fold and runs me-
FIGURE 3.
Resection of small carcinoma of the epiglottis edge.

FIGURE 4.
Resection lines for partial resection of the supraglottis. T h e epiglottis is split
in the midline. Depending on the extent of the tumor, the vestibular fold and
the aryregion can be included into the resection. (From Rudert H: Technique
and results of transoral laser surgery of supraglottic carcinoma. Adv Otorhi-
70 H.H. Rudert

FIGURE 5.
A, B, C, several resection types, depending on the extent of the supraglottic tu-
mors. Because of the characteristics of the CO;, laser, it is possible to resect the
tumor in parts. (From Rudert H, Werner JA: Endoskopische Teilresektionen mit
dem CO^-Laser bei Larynxkarzinomen. Laryngorhinootologie [Stuttgart, Thieme]
7 3 : 7 1 - 7 7 , 1 9 9 4 . Used with permission.)

dially to unite with the first vertical incision. The position and
course of the third incision line is determined by the extent of the
tumor. In this way, the tumor can be excised and removed well into
the healthy tissue.

RESECTION OF TUMORS OF THE INFRAHYOID EPIGLOTTIS


The resection of tumors of the infrahyoid epiglottis requires the in-
clusion of the pre-epiglottic space in the resected piece (Fig 6). This
can be achieved by cutting from the valleculae along the hyoepi-
Laser Surgery for Supraglottic Larynx and Hypopharynx Carcinoma 71

glottic membrane to the hyoid. From the hyoid bone, the incision
continues caudally, along the hyothyroid membrane, until the su-
perior edge of the thyroid cartilage is reached. From here, the en-
tire contents of the pre-epiglottic space, up to the anterior commis-
sure of the vocal cords, along the inside surface of the laminae of
the thyroid cartilage are removed with the laser. Separating the su-
prahyoid part of the epiglottis from the infrahyoid part after the
exposure of the hyoid is recommended to facilitate the resection
before the caudal dissection along the hyothyroid membrane and

FIGURE 6.
Resection lines marked in a median sagittal section of the larynx. T h e up-
per line marks the resection of a suprahyoid tumor, the other includes the
pre-epiglottic space in case of an infrahyoidal tumor. In case of a ventricu-
lar fold tumor, the inferior cut runs through the ventricle.
72 H.H. Rudert

the inner surface of the laminae of the thyroid cartilage. The dis-
section is then stopped either in the area of the vestibular folds or
of the ventricle, depending on the caudal extension of the tumor.

RESECTION OF FALSE CORD TUMORS


Tumors of the false cord can be better resected transorally than from
an external approach, if suitable resection techniques are applied.
The paraglottic space bordering on the thyroid cartilage must be
included in the resection as well as the pre-epiglottic space up to
the thyrohyoid membrane and the hyoepiglottic membrane. This
is only possible by using the same technique as in the resection of
tumors of the infrahyoid epiglottis, splitting the epiglottis from
above, exposing the hyoid and the upper rim of the thyroid carti-
lage from the vallecula, and resecting the entire false cord along
the inner perichondrium of the thyroid cartilage down to the Mor-
gagni ventricle. If needed, the resection could include the aryte-
noid cartilage as well (Figure 4 and Figure 6 ) . A block resection is
thereby achieved, which previously could only be achieved from
outside with great difficulty and a higher rate of morbidity.

RESECTION OF TUMORS OF THE ARYEPIGLOTTIC FOLDS


Tumors confined to an aryepiglottic fold can be removed in one
piece as an excisional biopsy. Depending on the cranial or caudal
extension, parts of the epiglottis and the arytenoid region may also
be removed.

RESECTION OF TUMORS OF THE POSTERIOR WALL


OF THE HYPOPHARYNX
These tumors, often difficult to reach by conventional external sur-
gical approaches, can be transorally resected very easily, if the pre-
vertebral ligament has not been invaded. The dissection in the
space between the tube of the pharynx muscles and the prevert-
rebral fascia is achieved in the cw mode with 2 W, just as if scal-
pel or scissors had been used. In this way, we have resected very
long tumors that had grown from the oropharynx down to the open-
ing into the esophagus, without having to have performed a tra-
cheotomy. Use of a feeding tube postoperatively is recommended
for a few days in these cases.

RESECTION OF TUMORS OF THE LATERAL WALL


OF THE HYPOPHARYNX
Only those tumors that have not penetrated through the tube of the
pharynx into the parapharyngeal space are suitable for transoral la-
Laser Surgery for Supraglottic Larynx and Hypopharynx Carcinoma 73

ser resection. First, the line of resection is marked on the mucosa


with the laser. The lateral wall of the hypopharynx is displaced
toward the midline with grasping forceps and then separated from
the parapharyngeal space with the laser beam (2 W), like using a
scalpel. One muscle fiber after another can be divided under the
microscope. Branches of the superior thyroid artery can be easily
recognized and coagulated before they are separated. The large pro-
cess of the hyoid bone must often be exposed when dealing with
tumors situated somewhat more anteriorly. It is not necessary to
cover the resulting defect. A feeding tube is inserted for a few days
for larger defects, more to prevent a collar mediastinitis than be-
cause of swallowing difficulties.

RESECTION OF TUMORS OF THE PIRIFORM SINUS WALLS


Tumors that have infiltrated the medial and anterior walls of the
piriform sinus can be resected most safely by partial resection of
the epiglottis on the tumor-involved side, coming down from above
as in supraglottic carcinomas. The large process of the hyoid bone
is used as a guide for the dissection along the hyothyroid mem-
brane to the superior rim of the thyroid cartilage and into the in-
ner perichondrium of the thyroid cartilage. The incision passes me-
dially from the aryepiglottic fold, including the resection of the ary-
tenoid region if necessary, and along the outer surface of the cricoid
cartilage. The dissection of the lateral wall of the piriform sinus is
performed like that of the lateral wall of the hypopharynx. In this
manner, the piriform sinus is lifted from its bed from all sides. The
resected part is grasped with large grasping forceps and extracted
cranially. The tip of the piriform sinus is extracted as well from
the wound surface and separated from its surroundings. In most
cases, the resection of the carcinoma in one piece is possible. At
the end of the operation, a feeding tube is inserted for a few days.

TREATMENT OF THE REGIONAL LYMPHATIC DRAINAGE


Of course the lymphatics must be cleared as part of a prophylactic
or therapeutic neck dissection, both in supraglottic carcinoma and
in hypopharyngeal carcinoma, if the condition of the patient al-
lows it. Unilateral carcinoma is treated with a contralateral neck
dissection if positive lymph nodes are found on the ipsilateral side.
Postoperative radiation is performed on supraglottic carcinomas if
more than one positive lymph node was found or in case of extra-
capsular spread. So far, we have applied postoperative radiation
therapy in all hypopharyngeal carcinoma if the general condition
of the patient allowed it.
74 H.H. Rudert

TABLE 1.
Results of Laser Surgery of 27 Supraglottic Carcinomas
1981-1993

Death Tu. Death Sec. Death Tu. Alive


T-Class. Pat. Rec. Unrel. Tu. Rel. NED

4 0 1 0 0 3
10 3 1 2 2 5
6 2 2 1 1 2
7 4 2 0 3 1
Total 27 9 6 3 6 11

NO: 14; Nl: 4; N2: 8; N3: 1


Follow-up minimum 40 months, mean 59 months. Completion of the study
31.12.96.

ONCOLOGIC RESULTS
A total of 30 patients with supraglottic carcinoma has been treated
between 1981 and 1993 with laser surgery in curative intention. A
follow-up was available in 27 patients (Table 1). Six of these pa-
tients died of causes unrelated to the carcinoma: four of advanced
cardiopulmonary disease, one of esophageal bleeding, and one of
liver failure. T h e statistics clearly show the risk factors of the pa-
tients, who were to a great percentage smokers and drinkers. They
also show that the transoral technique can be applied to multimor-
bid patients. The patients did not die of their carcinomas or of the
effects of the operation, but because of their other, mostly medical
problems, without the carcinoma affecting their quality of life.
Three patients died of a secondary carcinoma, six of their tumor,
of which the majority (four) died of the metastases and only two
of recurrence of the primary tumor. One patient is still alive with
his carcinoma, and 11 patients have been living without evidence
of disease for more than 3 years.
Most favorable are the results of the T and T carcinomas. Of
1 2

14 patients, two T cases died due to the carcinoma. The evalua-


2

tion of T and T carcinomas is difficult, because there are many


3 4

patients among them who have refused a laryngectomy or in whom


the treatment of the lymphatics remained incomplete due to other
medical problems. The number of recurrences and deaths due to
tumor causes is twice as high as in the T / T group. 1 2

2 3 , 2 4 4 7 25
In Europe, S t e i n e r , ' and Eckel and Thumfart have,
26 27, 28
along with R u d e r t and Rudert and W e r n e r reported transoral
Laser Surgery for Supraglottic Larynx and Hypopharynx Carcinoma 75

partial resections of supraglottic carcinomas; in the United States,


48
similar reports have come from Davis and H a y e s and Zeitels and
21 22
D a v i s . In 1994 Zeitels et a l . reported about 24 cases treated col-
48
lectively in Boston and Utah; in 1 9 9 5 , Davis and H a y e s reported
about 24 cases in Utah. Only once was a local recurrence diagnosed
in the cases treated in Utah; 21 of the 24 lived free of tumors for at
25
least 4 years. In 1 9 9 5 , Eckel and T h u m f a r t reported about 15
cases, none of which developed a primary tumor recurrence. In
47
1994, Steiner and A m b r o s c h reported about 79 patients ( T 12; a

T 42; T 13; T 12); local recurrences developed in 15. A salvage


2 3 4

laryngectomy was performed on five. S i x ( 8 % ) died of their tumors.


The 5-year overall survival rate according to Kaplan Meier was
6 7 % for T j and T carcinomas and 5 3 % for T and T carcinomas.
2 3 4

Results of laser surgery on hypopharyngeal carcinomas has as


49
yet only been reported by Steiner and A m b r o s c h . Our own to-
date unpublished results are based on a distinctly smaller group
49
of patients. In 1 9 9 4 , Steiner and A m b r o s c h described the course
of 73 therapeutically treated patients ( T 15; T 46; T 10; T 2); 71
a 2 3 4

remained locally free of tumors, two developed local recurrences,


10 metastases of the lymph nodes, nine distant metastases, 10 sec-
ondary carcinomas. Ten patients ( 1 4 % ) died of tumor-related
causes, 11 ( 1 5 % ) of secondary carcinomas or distant metastases,
16 ( 2 2 % ) of tumor-unrelated causes. The 3-year overall survival
rate was 7 2 % ; the 5-year overall survival, 5 9 % .
From 1991 to 1 9 9 4 , we treated 13 hypopharyngeal carcinomas
therapeutically with laser surgery (Table 2). Of these, nine were

TABLE 2.
Result s of Laser Surgery of 13 Hypopharyngeal Carcinomas
1981-1994

Alive with
Death Tu. Death Tu. Distant Alive
T-Class. Pat. Unrel. Rel. Metastesis NED

T a
2 0 0 0 2
T 2
9 2 2 2 3
T 3
2 0 2 0 0
Total 13 2 4 2 5
N0: 4; N1: 2; N2: 5; N3: 2.
Follow-up minimum 23 months, mean 33 months. Completion of the study
31.12.96.
76 H.H. Rudert

stage T and two each were stages T and T . Two patients died of
2 a 3

cardiopulmonary disease and hepatic coma, respectively, unrelated


to the tumor. Four patients died of tumor-related causes (three of
metastasis, only one of the primary tumor). Two patients are living
free of local tumors but with distant metastases; five patients are
living without a sign of any tumor, three of these longer than 2
years. These results cannot prove, of course, that limited hypopha-
ryngeal carcinomas show better oncologic results after laser surgery
than after laryngectomies, partial laryngectomies, and radiation.
But it can be carefully concluded that they are not worse than af-
ter laryngectomies and postoperative radiation.

FUNCTIONAL RESULTS
The main advantage of transoral resection techniques is the low
rate of morbidity according to the discussion in the literature. To
the patients, the laser surgical operation is not more invasive than
a microlaryngoscopy. They have no impairment of swallowing
functions and do not aspirate unless an arytenoid cartilage or the
entire supraglottic larynx up to the anterior commissure is re-
moved. Postoperative edema is minimal so that the airway is not
compromised. Because the superior laryngeal nerves are not dam-
aged by the transoral resections, the sensitivity of the pharynx re-
mains intact. The sphincter of the supraglottis during swallowing
remains functional. There is a certain tendency toward aspiration,
but only after the resection of an arytenoid cartilage, similar to what
occurs after an arytenoidectomy with bilateral recurrent nerve pa-
ralysis. We only performed a prophylactic temporary tracheostomy
on patients with poor pulmonary function, and occasionally after
bilateral neck resection in very old patients or those with a very
short neck. In 1994, a retrospective comparative examination of 20
5
patients " who had been operated on through an external approach
and 26 patients who had been treated by laser microsurgery,
showed that only five patients from the laser group, but 17 of the
conventionally operated group required tracheotomy. Twenty pa-
tients of the conventionally operated patients had aspiration pneu-
monia develop, but only three of the laser group. Eight of the
twenty conventionally operated patients had to be fed through a
nasogastric tube for longer than 2 weeks, compared to only four of
the laser group. These good functional results in patients after trans-
oral supraglottic laryngectomy were also observed by us in patients
after treatment of hypopharyngeal carcinoma. Only those patients
in whom an arytenoid cartilage had to be removed along with a
carcinoma of the piriform sinus needed a great amount of time un-
til they could swallow clear fluids without aspiration.
Laser Surgery for Supraglottic Larynx and Hypopharynx Carcinoma 77

CONCLUSION
Transoral laser surgery is a safe method for removal of T and T a 2

carcinoma of the supraglottis. The oncologic results are comparable


to the results after open partial larnygeal resections. The swallow-
ing and breathing functions are markedly better and the rate of mor-
bidity much lower, so that a tracheostomy is rarely necessary. We
also no longer observe an age limit.
The same statement applies to smaller hypopharyngeal carci-
noma, the laser surgical treatment of which in combination with
postoperative radiation seems to show comparable results with par-
tial laryngopharyngectomies. Given the low postoperative morbid-
ity and the lack of surgical alternatives to the laryngectomy, the
transoral laser surgical partial hypopharyngeal resection with the
goal of preserving the larynx should gain more importance.
Suitable instruments are the prerequisite for the performance
of transoral operations. Above all, a bivalved supraglottiscope must
be available, which can be inserted into the valleculae like an an-
aesthesiologic larynx spatula. A modern micromanipulator, which
allows dissection at the smallest focus of 0.25 mm with the low
wattage of 1-2 W in cw modus, is also helpful.
The resection techniques are best learned on the larynges of
cadavers.

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CHAPTER 5
The Special Child's
Airway From Nose
to Larynx
N. Wendell Todd, M.D.
Professor of Otolaryngology and Pediatrics, Departments of
Otolaryngology and Pediatrics, Emory University School of Medicine;
Chief of Otorhinolaryngology, Egleston Children's Hospital at Emory
University, Atlanta, Georgia

A irway compromise rostrad from the larynx typically mani-


fests as inhalatory low-pitched "snoring" stridor (stertor) dur-
ing sleep and/or obstructive apnea during sleep or the induction
of general anesthesia. The airway compromise is often relieved by
breathing through the mouth or by awakening. Many items can con-
tribute to the airway obstruction (Table 1). For the special child,
the list of obstructing items is longer, the obstructions are more of-
ten multiple, the obstructing site(s) are more challenging to iden-
tify and ameliorate, ethical dilemmas are more likely, the anatomi-
cal positions are more skewed from the adult "normal," and lumi-
nal calibers are smaller.
This chapter addresses both the common and uncommon life-
threatening "upper" airway conditions of special children. No eco-
nomic analysis (e.g., in terms of cost per disability-adjusted life
year, or mortality rate) is available. Instead, the approach is that of
a subspecialty physician attempting to minimize the suffering of
each individual special child. Randomized clinical trials are the
best method to advance evidence-based medicine but are not fea-
sible for special children's airway problems because they are un-
common and diverse, and often involve ethical issues. Cook book
or symptom-based treatment is not usually beneficial to these pa-
tients. Rather, the specific identification of obstructed site(s) and
recognition of etiologic item(s) more often lead to beneficial
therapy.
Advances in Otolaryngology-Head and Neck Surgery®, vol. 12
B 1
®1998, Mosby, Inc.
82 N.W. Todd

TABLE 1.
Obstructions of the Airway Rostrad from the Larynx

Allergic rhinitis
Midface hypoplasia
3 0
Deviated nasal septum, especially prevalent in cleft l i p and palate
patients
31
Intranasal stenosis (e.g., after nasal C P A P )
Foreign body
Nasolacrimal duct mucocele
Choanal atresia, stenosis
Adenoids
Cyst, polyp
Encephalocele
Teratoma, ectopic brain
Glossoptosis
Tonsils
Hypotonia of pharyngeal and tongue musculature
Thickened, poorly compliant soft tissues (e.g., mucopolysaccharidoses,
myxedema)
Small craniofacial dimensions
Tongue cysts, tumors, lingual thyroid gland
Neuromuscular dysfunction/incoordination
Inflammation, due to: mechanical trauma (e.g., suction catheter),viral or
bacterial infection, inhalant pollutants, chemical irritation (e.g., from
gastroesophageal reflux)

Airway patency during sleep is determined by three general


factors: airway size, neuromuscular activity, and neuromuscular
1
coordination. In infants, and to variable extents in older special
children, airway patency is more problematic because of small air-
way dimensions, high respiratory rates, nose breathing (so-called
obligate nose breathing, but probably better considered preferen-
2
tial or predominant nasal breathing ), and differences in sleep/
3
wake patterns and respiratory physiology.
Special children's airway problems are not limited to the
spaces laryngad from the nose. Multiple caudal sites may be com-
promised. Indeed, rare is the special child whose airway problem
can be rigorously deduced as being exclusively rostrad from the
4
larynx. Experience endorses the perspective of Friedman, et al,
that most children with airway compromise warranting endoscopy
The Special Child's Airway From Nose to Larynx 83

should have endoscopic assessment from the tip of the nose con-
tiguously into the bronchi: 1 1 . 5 % have lesions in more than one
anatomical site.

NOMENCLATURES
Universally meaningful terms are necessary. A "special child" is
one born extremely small (less than 1,500 g), is syndromic or dys-
morphic, or has neuromuscular impairment. The term "airway ros-
trad from the larynx" is preferable to "upper airway," because the
latter is neither precise nor unanimously defined. For example,
"upper airway" sometimes includes the larynx and even the bron-
chi (Table 2). Eponyms, often historic and honorable (e.g., Pierre
Robin), are no substitute for specific descriptive terms. Topo-
graphic and directional terms must be relative to a person, not nec-
essarily standing or supine. Hence, terms such as superior and in-
ferior, and above and below, are to be used cautiously.
Similar problems exist with the terms "normal" and "abnor-
mal." Is the special child "abnormal"? What is normal growth for
a child with Down's syndrome? This author prefers to avoid such
terms, electing instead to interpret tests and goals that are appli-
cable for each special child.

PATIENT ASSESSMENTS
HISTORY
What is the concern? Is it the cardiologist's worry that the pulmo-
nary arterial hypertension is disproportionate for the heart disease?
Does the family fear that the child will not be able to get another
breath during sleep? Is the endocrinologist wondering that chronic
airway compromise during sleep may explain the nonprogression
along the "normal" age/height graph?
What has the family noticed? During sleep, does the child
struggle to inhale, but no air flows (obstructive apnea)? Or, during
sleep, does the child sometimes make no motion whatever to
breathe? Can the child breathe normally when awake? When
awake, but supine? Does feeding or swallowing exacerbate the
breathing problem? Choking? Is the sleep breathing problem
present nightly? Is the problem inhaling, or exhaling, or both? Are
there birth marks—hemangioma? Cafe au lait? What does the fam-
ily wish? Is the family's depiction of the problem consistent or
vague? What other practitioners have been sought? Did the chiro-
practor manipulate the neck of a child with stigmata of Klippel-
Feil syndrome? Are there neurologic problems—seizures, a weak
hand, arm, or leg, bed-wetting, encopresis?
84 N.W. Todd

TABLE 2.
Nomenclatures

Term Meaning
Upper airway The supraglottic airway, i.e., the velopharynx,
32 33
oropharynx and h y p o p h a r y n x '
"from the nares or mouth to and including the
26 3 4 3 5
larynx" ' '
28 3 6 , 3 7
the trachea and a b o v e '
38
the bronchi and a b o v e
"special child" ex-premie ( < 1 . 5 g), syndromic, dysmorphic, or
neuromuscularly impaired
stridor noisy breathing, sufficiently intense to be heard at
the bedside
retrognathia posterior displacement of the chin; a more accurate
39
and inclusive term than micrognathia
macroglossia large tongue, either absolutely or relatively
glossoptosis tongue falling backward in the throat
sleep apnea lack of air movement for at least 10 seconds
Muller maneuver deep inspiration with partial occlusion of the nares
and mouth
obstructive sleep cessation of airflow for at least 10 seconds, despite
apnea continuing ventilatory effort, five or more
episodes per hour, usually associated with a
lowering of S a 0 of at least 4%
2

CPAP Continuous positive airway pressure


BiPAP Bi-level positive airway pressure: To a
spontaneously breathing patient, the delivery of
positive pressure via a mask during both
inhalation and exhalation cycles. Both the
inhalation and exhalation pressures can be preset.

PHYSICAL EXAMINATION
Both a general and airway-focused physical examination are ap-
propriate. What is the child's general status? Frail? Small for age?
Of short stature but obese? Ambulatory? Wheelchair bound? A bas-
ket case? That is literally, being carried about, unable to even roll
over? Measure the patient's length (height), weight, and head cir-
cumference, and plot these data on a normative growth chart and,
with prior data, check the progression.
Is the midface hypoplastic? Is there air flow through each
nostril, at the cotton wisp test? Is the mandible small? Is the
The Special Child's Airway From Nose to Larynx 85

tongue confined within the arch of the mandible? Is the floor of


the mouth elevated? Are the faucial tonsils large or small? Is the
velum intact or cleft? Although many physicians diligently note
velar motion when the patient is gagged, velar motility is better
assessed by fiberoptic endoscopy of the dorsum of the velum.
Tongue fasciculations? Tongue motility? If there is a question of
abnormal mobility, digitally palpate the mouth and pharynx
(including the posterior wall of the oropharynx). Are there neck
masses, congenital dimples, tags, or fistulae? Are the neck mo-
tions intact? Can the neck be flexed so that the chin touches the
sternum? Can the neck be rotated so that the face presents at least
60 degrees to each side of neutral? Can the head be tilted? Can the
head and neck be positioned so as to sniff a rose (also described
as the neck position of a barking dog)? Also, take time observing
and feeding the child.

ENDOSCOPY
Just as the parents' description and the clinical physical examina-
tion provide information about the child's breathing problem, so
does visualizing the interior of the breathing passages. Note, how-
ever, the obvious: endoscopy reveals the interior perspective and
does not provide information about subjacent tissues. For example,
endoscopy may reveal that the nasal vestibule is narrowed but only
hint at the fact that the narrowing is due to bony stenosis of the
pyriform aperture. Careful palpation, CT, and surgical exploration
identify the correct diagnosis.
Flexible fiberoptic scopes have revolutionized endoscopic as-
sessment of the airways. Steerable scopes smaller than 1 mm in
diameter are available. In general, the smaller the diameter of the
scope, the poorer the resolution, the more graininess, the less steer-
able (operator-controlled off-axis bending), the dimmer the illumi-
nation, the less the suction capability, and the greater fragility and
higher cost of the instrument. Notwithstanding these marvelous in-
struments, user training and experience are challenging. Few en-
doscopists have a practical working knowledge of (1) the periph-
eral distortion of the optical image, (2) the imprecision of estimat-
ing the size of items viewed, and (3) that "what you see, depends
on where you stand," that is, the image is determined by the posi-
tion of the tip of the scope. Change the angular orientation of the
tip of the scope, its depth in the lumen, or its position within the
lumen and a very different view is appreciated. A snapshot is not
sufficient; rather, multiple contiguous images are demanded.
The endoscopic appearance of the interior of the nose is not
affected by neck or mandible position or by swallowing or phonat-
86 N.W. Todd

ing or the Miiller maneuver. In contrast, the velum and entire phar-
ynx and tongue are greatly affected, and endoscopy should include
the evaluation of these effects on the airway lumen. Also, fiberop-
tic endoscopy may include assessing the effects of sedation or an-
esthesia; to our diagnostic advantage, sites that intermittently ob-
struct may thus be recognized. Using these techniques, faucial ton-
sils that were unimpressively small at intraoral inspection may be
appreciated to be important obstructions.
The cervical spine may be at risk during endoscopic and
other procedures in "special" children. Patients at extra risk
include those with Down's and Hurler's syndromes, as well as
those with skeletal dysplasia syndromes (e.g., Morquio's, spondy-
loepiphyseal dysplasia, pseudoachondroplastic dysplasia,
Klippel-Feil). Although hyperextension of the neck is sometimes
advocated for both rigid bronchoscopy and endotracheal intuba-
tion, the sniff position is generally preferable, particularly in
special children, for two reasons. The genioglossus muscle, which
helps keep the tongue from falling posteriorly, is laxed by neck
extension, and by anesthesia and sedatives ("Neck flexion reflexly
5
activates genioglossal discharge. . . , " ) A second reason to use
the sniff position is safety. Laxness of the cervical spine, espe-
cially recognized in patients with Down's syndrome, may result
in the odontoid process not only being aimed at the medulla
oblongata, but damaging it.

IMAGING
Traditional plain radiographs, fluoroscopy, CT (including three-
dimensional reconstruction), and MR studies all have roles in as-
sessing the airway of the special child. The role typically to con-
firm a diagnostic impression (from the aggregate of history, physi-
cal, and endoscopy), and helping to plan a therapeutic maneuver
(e.g., whether to approach choanal atresia transpalatally or trans-
nasally). Conferring with the radiologist is the optimal means of
deciding the appropriate study for a particular patient.
When a diagnostic impression is formed before imaging is ob-
tained, consider other pertinent information that imaging may pro-
vide. For example, if the diagnostic impression is nasal pyriform
aperture stenosis, then obtaining images that include the midface
and skull is reasonable, because the nasal deformity is associated
8
with absence of the anterior pituitary gland.
A false positive study, especially common in young infants im-
aged during exhalation with the neck flexed, is prominent retro-
pharyngeal soft tissues. Imaged during inhalation with the neck ex-
The Special Child's Airway From Nose to Larynx 87

tended, normal prevertebral soft tissue (cephal to the larynx) can


be up to 1.5 times the anterior-posterior diameter of the adjacent
7
vertebral body. Fluoroscopy, CT, or MRI may sometimes be needed
to assess retropharyngeal soft tissues in special children.

POLYSOMNOGRAPHY
Most clinicians consider partial airway obstructions to have the
same consequences (hypoxemia and sleep disturbance) as com-
plete airway obstructions during sleep. Decreases in hemoglobin
oxygen saturation ( S a 0 ) below 9 0 % may be clinically significant,
2
8
and below 8 0 % are significant.
Concerns about polysomnography in children, not only special
children, include (1) no universal agreement on definitive stan-
dards for normal and abnormal respirations in different stages of
sleep; (2) the assumption that sleep in the laboratory is represen-
3
tative of the patient's usual sleep; and, (3) expense. There are no
first-night second-night polysomnography repeatability studies in
a pediatric population. The assumption is that the sensitivity of
polysomnography on a single night's study is sufficient to identify
9
the patient who suffers from frequent sleep apnea.
Interpreting the polysomnograms of children requires extra
considerations. The respiratory physiology of premature and term
infants, and probably of special children beyond infancy, differs
from adults in four ways. First, brain neural networks that initiate
and control breathing are incomplete even in term infants. Second,
there are differences in chemoreceptor sensitivity and brain activ-
ity, with age-dependent differences in response to hypoxia. Third,
respiration can be depressed by afferent impulses originating in the
upper airway. Fourth, the coordination between posterior cricoary-
3
tenoid muscles and diaphragm is incomplete. Normal infants tend
to enter rapid-eye-movement (REM) sleep directly, rather than pro-
10
gressing first through non-REM s l e e p .
Notwithstanding the concerns about test-retest agreement, nor-
mative data, and differences in respiratory physiology of infants
and adults, the general classification of sleep apneas seems appro-
priate to all ages of patients. The central apneas involve two sub-
types: (1) true central neurologic abnormalities with insensitivity
or adaptation to hypercapnia and/or hypoxia; and, (2) the neuro-
muscular disorders that include bulbar palsy, the muscular dystro-
phies, and so on. The obstructive apneas involve congenital or de-
velopmental airway obstructions (Table 1). Confusingly, even at
polysomnography, the distinction between central and obstructive
apnea is not always straightforward.
88 N.W. Todd

DIFFERENTIAL DIAGNOSIS
Table 1 shows an approach to the various diagnostic considerations
for airway compromise rostrad from the larynx. Multiple site of in-
volvement may exist rostrad from, within, and caudal to the lar-
ynx. Some obstructions are more assuredly addressed than others.
The cross-check principle, that all data from various sources
(history, physical, endoscopy, imaging, polysomnography) as-
semble into a meaningful whole, is especially applicable to the di-
agnosis of airway problems in special children. The data in these
special children often are inexact, accurate diagnoses are elusive,
and therapeutic endeavors are risky and ethically problematic. In
these regards, the challenges are daunting—just as daunting as ap-
plying the cross-check principle to a battery of audiologic data, or
for the aircraft pilot integrating continuously updating information.
If the history is variable and/or inconsistent with the other data,
then consideration should be given to a disordered parent-child re-
lation (e.g., Munchausen syndrome by proxy, child abuse).
Hundreds of syndromes involving the nose and throat are rec-
11
ognized. About 44 are associated with short or small nose and/or
anteverted nostrils; about 15 with cleft nose or bifid tip of nose;
about 12 with hypoplastic, small, flared nostrils or coloboma of
nostrils; and, about 12 with choanal atresia or stenosis. About 191
syndromes are associated with congenital anomalies of mouth, pal-
ate, and pharynx. Table 3 depicts some of the syndromes.

THERAPEUTIC INTERVENTIONS
ETHICS
Is it appropriate to consider a rigorously defined nonnormal
polysomnogram as "OK" for a now-tracheostomy-decannulated
CHARGE association child, whose family refuses the only remain-
ing therapy (another tracheostomy)? Or, considering management
options, what was the wisdom of obtaining that polysomnogram?
Why prolong the suffering of the child? Considering quality of life
issues for the special child with a tracheostomy, and the family's
quality of life, when is it "right" to perform a tracheostomy, and
when is it "right" to not perform a tracheostomy? For a child with
Down's syndrome, is it appropriate to use a standard growth chart,
or a growth chart based on Down's syndrome children of a genera-
tion ago? For each of these questions, the author's only answer is
to carefully and repeatedly work with the patient, family, pediatri-
cian, and others appropriately involved, to arrive at a consensus
with which all are comfortable.
TABLE 3.
Some Syndromes That Have Obstructive Apne a as a Finding, and Contributors to the Obstruction
Choanal Cranial
Hypoplastic atresia/ base Hypotonic Macro-
Syndrome Retrognathia maxilla stenosis anomaly pharynx glossia Other anomalies
Achondroplasia + + + Foramen magnum
Apert's + + + Trachea
Beckwith-Wiedemann +
Camptomelic + Trachea, bronchi, CNS
CHARGE + + CNS, ear, eye
Crouzon's + + + Trachea
de Lange + + CNS
Down's + + + + Lax cervical spine
Fetal alcohol + + Microcephaly
Fetal hydantoin + CNS
Hallermann-Streiff + +
Hemifacial microsomia + + Pharyngeal asymmetry
Holo-prosencephaly + + + + CNS
Larsen's + Dislocations, cleft velum
Marshall-Smith + + + + + CNS
Nager's + + + +
Otopalatodigital + + Cleft palate
Pfeiffer's + + + Trachea
Prader-Willi + Marked obesity, CNS
Robin sequence (isolated) +
Rubinstein-Taybi + + + + CNS
Shprintzen + + + Cardiac (conotruncal)
Stickler + + + Eye
Treacher Collins' + + + +
11
About 275 syndromes involve the nose and throat.
40
(Adapted from Shprintzen in Sher. By permission).
90 N.W. Todd

MANAGEMENT

Remove Obstruction
The most gratifying management of airway obstruction is to remove
the obstruction, e.g., obstructing adenoids and tonsils, foreign bod-
ies, choanal atresia, pyriform bony aperture stenosis, large naso-
lacrimal duct mucoceles, or nasopharyngeal teratoma. Notwith-
standing the gratifying results, the postoperative course can be
stormy. For example, patients with cerebral palsy undergoing ton-
sillectomy and adenoidectomy often have postoperative breathing
and feeding problems, so that hospitalization for them averages
12
nearly 1 w e e k .
The most difficult obstructions of the airway laryngrad from
the nose are those related to chronic inflammation or neuromus-
cular dysfunction. Mucosal inflammations attributable to viral or
bacterial infections, allergic response, mechanical trauma (e.g.,
repeated suctioning of the nose and pharynx with a catheter),
gastroesophageal reflux all the way into the choanae, inhalant
pollutants, and the edema of hypothyroidism are often sneaky
and may involve more than one etiology. Anecdotally, patency of
the inflamed nasal airway may be helped by injecting the inferior
turbinates with depot triamcinolone (10 mg/mL) after thoroughly
shrinking the turbinates with sympathomimetics, so that the risk
of vascular embolization of particles to the brain and eyes is
13
supposedly r e d u c e d .
For patients with Down's syndrome with obstructive sleep ap-
14
nea, Lefaivre et a l . report that "an aggressive surgical approach
aimed at correcting all anatomic abnormalities associated with up-
per airway obstruction was applied successfully" to seven chil-
dren. At a single operation for each patient, combined soft-tissue
and skeletal alterations included tonsillectomy (5), adenoidectomy
(6), tongue reduction (6), tongue hyoid suspension (4), septoplasty
(1), uvulopalatopharyngoplasty (7), inferior turbinectomy (6), max-
illary or midface advancement (2), and genioplasty (2). The patients
had intensive care for a mean of 10.3 days.
Numerous surgical maneuvers for positioning the glossoptotic
tongue to achieve airway patency have been made. In a consecu-
tive series of 53 infants with Robin sequence (micrognathia, wide
U-shaped cleft palate, and upper airway obstruction), nine got tra-
cheotomy and 24 got glossopexy. Twenty had "definitive" manage-
ment with a nasopharyngeal tube (stabilized with tape). The single
most successful procedure, at least short term, was nasopharyngeal
15
intubation.
The Special Child's Airway From Nose to Larynx 91

Bypass With Tube Through Obstructed Site


This maneuver can afford dramatic relief of airway compromise.
The problems relate to accurate diagnosis, optimal positioning of
the tube(s), and stabilizing the tube(s) to avoid displacement and
local inflammation. Fiberoptic endoscopy through the tube is nec-
essary to determine optimal positioning in special children. Even
in standard adults, rote placement of nasopharyngeal airways was
16
too caudal or too rostrad in three fourths of patients.
In highly selected patients, several months of a hard-wired na-
sopharyngeal breathing tube can be quite useful. The tubes are seg-
ments of "endotracheal tubes" that extend from the pharynx to the
posterior extent of each nasal vestibule (Fig 1). Stabilization is with
a loop of cardiac pacemaker wire routed posterior to the nasal sep-

FIGURE 1.
Plain lateral radiograph of the head of a 7-month-old child with Apert's
syndrome. (See Challenging Airway, Worsened by Closure of Cleft Palate.)
Note the hard-wired nasopharyngeal airway tubes, the intracranial shunt
hardware, and the hardware from the craniofacial procedure.
92 N.W. Todd

turn, where the wire penetrates the wall of each tube, thence rout-
ing through each tube's lumen anteriorly, where each wire is in-
serted through the floor of the vestibule, to be tied "under" the up-
per lip, immediately anterior and caudal to the anterior nasal spine.
The patients can be fed by mouth. Cleansing of the tube lumen is
with saline drops, and gently suctioning with a catheter (just the
length of the tube), or gently puffing air with a bulb syringe. Con-
trary to the admonition that choking and vomiting are induced if
the tube is caudal to the epiglottis, at least some "special" children
tolerate such position.
Bypass With Tracheostomy
Although tracheostomy involves many practical and quality-of-life
issues for special children, it is necessary for some patients.

POSITIVE INTRALUMINAL AIRWAY PRESSURE


The long-term compliance with nasal continuous positive airway
pressure (CPAP) in special children is unknown. Of 125 adults with
obstructive sleep apnea, only three fifths were known to be con-
1 7
tinued users (mean follow-up 14.5 months; range 2 - 3 8 ) .

GROWTH CONSIDERATIONS
18
Children with obstructed airways are usually small in stature.
Such a statement is reminiscent of an old adage: a child who is
growing well but snores some, is doing OK. That is, do not worry
about sleep apnea in such a child. Sleep disturbances are associ-
ated with abnormalities in growth hormone secretion, which is
closely linked to the first period of slow-wave sleep (i.e., stages 3
19
and 4 of non-REM s l e e p ) . Presumably, the child who has such
troubled breathing that slow-wave sleep is not attained does not
secrete the normal spikes of growth hormone. Hence, the child's
height does not track typically with age.
The larynx of Homo sapiens is more caudal in adults than in
newborns. The laryngeal descent is a feature that distinguishes man
20
from monkeys and other m a m m a l s . The larynx descends one half
vertebral body from the seventh to ninth months of gestation. Nev-
ertheless, in the term newborn, the tip of the epiglottis is posterior
to the soft palate (in the so-called intranarial position), and the true
vocal cords are at the level of the junction of C1-C2. The larynx
descends nearly two vertebral bodies by age 2 years. In adults, the
true vocal cords are at the level of the junction of vertebral bodies
21
C4-C5.
Newborns with a small mandible do not necessarily have
growth catch-up with resolution of either the airway obstruction
The Special Child's Airway From Nose to Larynx 93
22
or the micrognathia. In normal individuals, the angle joining the
posterior/caudal borders of the mandibular ramus and body
changes from 130 degrees to 100 degrees from the newborn to the
23
adult.
In adults with vocal disturbances, a peculiar orientation of the
hyoid bone to the thyroid cartilage, in which the larynx is enclosed
in the concavity of the hyoid, may represent persistence of an em-
24
bryonal relation. Noted in some "special" children, such laryn-
geal enclosure may be exaggerated by long-term orotracheal intu-
bation. Other than a contributor to consternation in the care of
some children, the clinical significance of laryngeal enclosure by
the hyoid is unknown.

INTERACTIONS OF MULTIPLE OBSTRUCTIONS


Interactions of airway obstructions have a superadditive detrimen-
tal effect. Nasal obstruction may cause a reflex change in the tone
25
of the pharyngeal musculature, in addition to activating the "na-
sopulmonary reflex" resulting in hypoxemia. Lung surfactant and
mucociliary clearance are altered. Humidification of inhaled air
may reverse the hypoxemia and decreased lung compliance seen
26
in clinical and experimental nasal obstruction.
Pulmonary arterial hypertension can occur in the setting of
chronic airway obstruction. The mechanism is obstruction-induced
hypoxemia and hypercarpnia, with resultant pulmonary vasocon-
striction and increased pulmonary arterial resistance, further ex-
acerbated by sympathetic activity prompted by hypoxemia and
27
hypercarpnia. Children with Down's syndrome are especially
28
susceptible to pulmonary hypertension. Unfortunately, the elec-
trocardiogram is neither sensitive nor specific for indicating
elevated pulmonary arterial pressure. A high index of clinical sus-
picion prompting echocardiography is the key to timely diagnosis.
High pulmonary arterial pressure unresponsive to increased F I 0 , 2

is a problem that cannot be fixed.

EMERGENT CALLS ABOUT THE AIRWAYS OF SPECIAL CHILDREN


When the anesthesiologist or intensivist summons emergency help,
controlling a special child's difficult airway is a tremendous chal-
lenge. Acutely bypassing with a tracheostomy may be the only fea-
sible option. However, this author has been gratified with some ba-
sic maneuvers. One, applicable in the child with a normally mo-
bile cervical spine, is exaggerating the sniff position and displacing
the tongue laterally, then performing endotracheal intubation
through a straight laryngoscope. Two, is placing a tube through the
94 N.W. Todd

nose and pharynx, so that the tip of the tube is adjacently rostrad
from the arytenoids. Rather than relying on "rules of thumb" to es-
timate the length of such a tube, use a fiberoptic scope to assess
tube position. Another maneuver is the combination of adequately
decongesting the nasal mucosa and suctioning secretions, then in-
tubating the trachea "over" a flexible fiberoptic scope. Until a tra-
cheostomy can be placed, a colleague can digitally stabilize the tip
of an "endotracheal" tube in the introitus of the larynx, so that the
patient is ventilated.
Most, but certainly not all, of these emergency summons can
be avoided by a thoughtful preoperative assessment. The three
more subtle problems are limited cervical spine mobility, "high and
anterior" larynx, and limited mouth-opening mobility (e.g., due to
ankylosis of the temporomandibular joints, or faucial stenosis], A
combination of two (or more) of these snakes may well make oro-
tracheal intubation impossible. Difficult intubations have an ana-
tomical abnormality, even if that abnormality is not obviously rec-
ognizable.

ILLUSTRATIVE PATIENT V I G N E T T E S
BAD AIRWAY; DIFFICULT ETHICS
The fetal ultrasound study revealed multiple abnormalities, includ-
ing absent corpus callosum. The mother (a nurse) disagreed with
the father's admonition to have a "therapeutic abortion," or else
he would leave the home. Delivered after 33 weeks' gestation, the
baby had features of Opitz-Frias syndrome, the most desperate
problem being a glossoptotic airway. Trials of positioning and na-
sopharyngeal positive pressure did not relieve the intermittent "dy-
ing spells." After soul-searching, deliberate discussions with the
neonatologist, family, and ethicist, the child was taken to the op-
erating room for airway endoscopy and airway improvement, rec-
ognizing that tracheostomy may be required. A severely glossop-
totic airway, made more difficult by the small mandible, was found.
A tracheostomy was placed, while the child was ventilated through
a rigid bronchoscope.
Recall the initial meaning of the term patient: "one who suf-
fers, endures, or is victimized."

CHALLENGING AIRWAY, WORSENED BY CLOSURE OF CLEFT


PALATE
A term newborn, the seventh child in the family, had findings of
Apert's syndrome: small flat midface, hypertelorism with bulging
eyes, craniosynostosis of the coronal sutures resulting in
The Special Child's Airway From Nose to Larynx 95

brachycephaly, cleft palate, and "mitten" syndactyly of all four ex-


tremities. He had intermittently obstructed breathing, most impres-
sive during feeding. Bilateral nasopharyngeal tubes were placed at
age 1 month. (See "Bypass with Tube through Obstructed S i t e " for
technique of hard-wiring nasopharyngeal tubes.) He could then
feed satisfactorily and went home. At age 6 months, the infant had
a craniofacial procedure and placement of a ventriculo-peritoneal
shunt (Figure 1). The next month, the nasopharyngeal tubes were
removed. These had to be replaced at age 12 months when he had
persisting nose and pharyngeal obstruction, which initially seemed
to be a routine "viral respiratory infection." At age 19 months, with
the child exhibiting good growth and neurologic status, the sec-
ond set of nasopharyngeal tubes were removed.
At age 30 months, the cleft palate was closed. Airway difficul-
ties gradually worsened, and he failed to gain additional weight.
At age 3 years, he had pneumonia, was identified as having severe
tracheomalacia, and got a tracheostomy. In the subsequent year, he
had acute intestinal obstruction related to malrotation, and he un-
derwent a LeFort III midface advancement procedure. At age 6V2
years, the tracheomalacia resolved, and he tolerated tracheostomy
decannulation. The family regards the tracheostomy years as the
most arduous.

GRAVITATIONAL GLOSSOPTOSIS
A 7-week-old boy was emergently hospitalized because of troubled
breathing so frightening that the parents, pediatrician, and cardi-
ologist feared that he would not get another breath. A twin, the in-
fant had been delivered after 33 weeks' gestation, weighing 1.4 kg.
Tetralogy of Fallot had prompted Blalock-Taussig shunting at age
4 weeks. The child was discharged home on the eighth postopera-
tive day. Among the instructions for home care was the precaution
that he sleep supine (because the risk of "sudden infant death syn-
29
drome" is increased in prone-sleeping infants). He was given
medicines for presumptive gastroesophageal reflux.
Otolaryngic emergency consultation at age 7 weeks, when the
child had been transported by ambulance from the cardiologist's
office to the hospital, revealed inhalatory low-pitched stridor (ster-
tor) with frequent total airway obstruction during inhalation. When
placed prone, or into a lateral decubitus position, the child
breathed comfortably. When he held his mouth open, the breath-
ing was fine. He had dysmorphic features reminiscent of Noonan's
syndrome. His weight was 3.0 kg. Flexible fiberoptic nasopharyn-
goscopy revealed the tongue to be too posterior, so as to touch the
96 N.W. Todd

posterior wall of the pharynx and occlude the airway, but only
when the infant was supine. The pharyngeal airway was patent
when the baby was positioned into a lateral decubitus position. The
larynx appeared normal.
After verifying that the child did satisfactorily for 2 nights in
the hospital, he was sent home. The instructions were to avoid the
supine position, and to use the lateral decubitus position. In the
subsequent 5 weeks, he did well, became stronger, gained an addi-
tional 1.0 kg, and became able to sleep supine.

MISDIAGNOSIS, PECULIAR CONSTELLATION, SATISFYING RESULT


Consultation was requested on a 16-month-old boy because of
troubled breathing, especially during sleep. He was much worse
in the couple of weeks after repair of cleft palate (wide, of the en-
tire secondary palate). He had been born at term. Other malforma-
tions included minimally cyanotic conotruncal heart disease, low-
set ears, and a short, webbed neck. In the operating room, the sur-
prise findings were bilateral choanal atresia, corrugated vomer of
6-mm thickness, plus glossoptosis. After opening of the choanal
atresia and placement of a nasopharyngeal stent tube, he was much
better. The stents were removed 2 months later. Respiratory dis-
tress after cardiac surgeries prompted airway endoscopies (includ-
ing bronchoscopy) at ages 22 and 34 months. Choanal narrowing
prompted repeat surgery (without stent placement) at age 45
months. By age 5.5 years, he had had three sets of tympanostomy
tubes.
Just prior to his sixth birthday, persistent infection in a negli-
gibly ventilated but perfused left lung prompted hospitalization for
assisted ventilation. Repeated attempts at discontinuing the endo-
tracheal tube failed. Endoscopies again suggested elements of na-
sal and glossoptotic obstruction; a nasopharyngeal tube was placed.
He then tolerated removal of the endotracheal tube, and subse-
quently was "the healthiest that he's ever been" after pneumonec-
tomy. Four months later, the family reluctantly agreed to removal
of the beloved nasopharyngeal tube. This active child is an enthu-
siastic special education student.

"ROUTINE" TONSILLECTOMY AND ADENOIDECTOMY; SPECIAL MAY


NOT BE OBVIOUS
A 4V2-year-old boy was referred because of polysomnogram-
documented obstructed sleep apnea, so severe that bi-level posi-
tive airway pressure (BiPAP) was required nightly. Four months
earlier, he had had a routine tonsillectomy and adenoidectomy, re-
The Special Child's Airway From Nose to Larynx 97

suiting in several weeks' respite from all troubled breathing but


with velopharyngeal insufficiency speech. He had a somewhat
coarse facial appearance, slightly low-set pinnae, and pectus exca-
vatum. He could voluntarily open his mouth only about 2.5 cm;
when gagged, the right and left "lateral pharyngeal bands" met in
the midline. Additional physical findings, corroborated during ex-
amination with a general anesthetic, included bilateral faucial ste-
nosis so that both the tongue and velum were tethered, prominent
adenoid tissue filling the lateral one half of each choana, and hy-
poplasia of the musculus uvulae. Triamcinolone (10 mg/mL) was
injected into cicatricial tissues.
Two months later, the child could nap comfortably, but he con-
tinued to require BiPAP during nighttime sleep. The velopharyn-
geal insufficiency speech had resolved, and he could fully open
his mouth. An additional triamcinolone injection was done of the
scarred faucies. At his fourth birthday, the pharyngeal stenosis ap-
peared mild, and the polysomnogram showed central apnea, not
obstructive apnea as had been noted previously. Magnetic reso-
nance imaging revealed Arnold-Chiari type I malformation, for
which the child underwent decompression of the foramen mag-
num. Central apnea continued 18 months later, and comfortable
sleep was afforded only with BiPAP.

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30. Josephson GD, Levine J, Cutting CB: Septoplasty for obstructive sleep
apnea in infants after cleft lip repair. Cleft Palate Craniofac J 33:473-
476, 1996.
31. Loftus BC, Ahn J, Haddad J Jr: Neonatal nasal deformities secondary
to nasal continuous positive airway pressure. Laryngoscope 104:1019—
1022, 1 9 9 4 .
32. Strallo PJ Jr, Rogers RM: Obstructive sleep apnea. N Engl J Med
334:99-104, 1996.
33. Strohl KP: Upper airway diseases, in Bennett JC and Plum F (eds):
Cecil Textbook of Medicine. Philadelphia, WB Saunders, 1996, pp
449-502.
34. Spraycar M (ed): Stedman's Medical Dictionary, 26th ed. Baltimore,
Williams & Wilkins, 1 9 9 5 , p 40.
35. Finucane BT, Santora AH: Principles of Airway Management, ed 2. St.
Louis, Mosby-Year Book, 1996, pp 302-303.
36. ICD-9CM (International Classification of Diseases, 9th Revision, Clini-
cal Modification, Fifth Revision). Los Angeles, Practice Management
Information Corporation, 1997, pp 219-224.
37. Pransky SM, Grundfast KM: Differentiating upper from lower airway
compromise in neonates. Ann Otol Rhinol Laryngol 94:509-515, 1985.
38. Thomas CL (ed): Taber's Cyclopedic Medical Dictionary, ed 18. Phila-
delphia, FA Davis, 1997, p 2 0 3 1 .
39. Norton ML: Micrognathia, cervical spine, and other bony consider-
ations in the difficult airway, in Norton ML, Brown ACD (eds): Atlas
of the Difficult Airway. St. Louis, Mosby-Year Book, 1991, pp 89-103.
40. Sher AE: Obstructive sleep apnea syndrome: A complex disorder of
the upper airway. Otolaryngol Clin North Am 23:593-608, 1990.
CHAPTER 6
What's New in the
Management of
Respiratory
Papillomatosis?
Frank L. Rimell, M.D.
Assistant Professor, Otolaryngology - Head and Neck Surgery and
Pediatrics, University of Minnesota School of Medicine, Minneapolis

R ecurrent respiratory papillomatosis (RRP) is primarily a dis-


ease of early c h i l d h o o d — 7 5 % of diagnoses are made in chil-
dren younger than 5 years of age. The annual incidence of RRP is
estimated at 1 , 5 0 0 to 2 , 5 0 0 new cases per year in the United States.
Few diseases in the field of head and neck medicine are as frus-
trating to treat as RRP, because management of this disease has
changed so little during the last 50 years. Treatment still consists
essentially of operative debulking and waiting for viral remission.
Nevertheless, some progress has been made in techniques for
anesthesia and operative debulking and in understanding the ba-
sic disease process. Furthermore, recent interest and funding by the
Centers for Disease Control and Prevention (CDC) and the RRP Task
Force have resulted in studies that should enhance our knowledge
1
of RRP and improve treatment of this disease.

PATHOLOGIC CHARACTERISTICS OF RRP


Recurrent respiratory papillomatosis is caused by the human pap-
illoma virus (HPV), which is a double-stranded DNA virus consist-
ing of 8 , 0 0 0 base pairs. The viral DNA is believed to be organized
into eight open reading frames, six early regions designated by the
letter " E , " and two late domains designated by the letter " L . " The
" E " regions are involved in viral DNA replication. The " L " regions
encode the capsid protein that is involved in epithelial penetra-
tion (infection), which allows the " E " regions to replicate and pro-
Advances in Otohiryngology-Head and Neck Surgery®, vol. 12
®1998, Mosby, Inc.
102 F.L. Rimmell

duce more virus particles. This process results in the epithelial


changes seen clinically as a papillomatous growth.
More than 90 types of HPV are known, designated by numbers
such as HPV 16, HPV 3 1 , etc. Those HPV types with closer num-
bers are more closely related. Thus, for example, HPV 16 and HPV
18 are quite similar to each other and dissimilar to HPV 3 1 .
Human papilloma virus 6 and HPV 1 1 , which are in the same
grouping, are known to be responsible for the majority of RRP in-
2-7
fections. In addition, we have demonstrated that HPV 16,
8
although very rarely, can be a cause of RRP.
Studies in the field of gynecology show that the type of HPV
infecting the genital tract affects the clinical course of infection,
and that HPV types 16 and 18 are associated with the highest risk
9
of squamous metaplasia and malignancy. Human papilloma virus
types 16, 18, and those in the 30 group have been found in signifi-
10
cant proportions of laryngeal carcinoma c a s e s . However, HPV has
11
also been found in the normal larynx of cadavers. Because HPV
only grows in squamous epithelium, spread of the virus down the
tracheobronchial tree depends on squamous metaplasia.
Recurrent respiratory papillomatosis typically goes into re-
mission, but the time to remission is unpredictable. The finding
that RRP can also cause squamous metaplasia and progression to
7
squamous cell carcinoma has lead to the belief that subclinical
RRP disease may be responsible for some cases of laryngeal carci-
12
n o m a . It has been our clinical experience that progression of RRP
in adults may lead to squamous cell carcinoma in the larynx or
lung, whereas progression in children usually leads to squamous
cell carcinoma in the lung.

JUVENILE AND ADULT DISEASE


Recurrent respiratory papillomatosis has been traditionally classi-
fied into juvenile and adult types, with juvenile being highly pre-
dominant. We have noted two peaks for presentation of the dis-
ease in adults: in younger adulthood (the 20s) and in older adult-
hood (the 40s). Some adults with RRP actually have juvenile
disease that persisted into adulthood. Others who present with RRP
in the third or fourth decade of life have juvenile disease that went
into remission during puberty and is now recurring—a course that
10
has been well documented. In fact, it has been shown that when
RRP is in remission (the patient has no visible lesions), the HPV
can still be found in the airway when specimens are analyzed by
13
polymerase chain reaction (PCR) t e c h n i q u e s . It is rare for adult
disease to result in airway obstruction but it does occur.
Management of Respiratory Papillomatosis 103

BENIGN AND AGGRESSIVE DISEASE


Some patients will die of RRP. Based on our experience, we have
further classified RRP as benign or aggressive depending on its
course. Benign disease goes into remission by puberty in the case
of juvenile presentation, or is limited to the larynx and subglottis
in the adult or child, and does not require a tracheotomy. Aggres-
sive disease is characterized by one or more of the following:
spread to the carina or beyond, treatment with more than 50 sur-
gical procedures, need for tracheotomy, persistence into adulthood,
or metaplasia to carcinoma in situ or squamous cell carcinoma. Pa-
tients with aggressive disease have a poor prognosis and are more
7
likely to die of disease.
Factors in addition to aggressive disease that complicate man-
agement of RRP or lead to a poor prognosis include age of onset
and infecting HPV type. Chipps et al. reported on four children
who presented with disease before 6 months of age, and all four
14
children died of d i s e a s e . Mounts and Kashima demonstrated that
in a mixed group of patients, some with juvenile and some with
adult disease, those whose RRP was due to HPV 6C (believed to be
the same type as that currently designated as HPV 11) required
15
more frequent operations and needed tracheotomy more often.
Our studies have shown that patients with RRP due to HPV 11 are
much more likely to have airway obstruction and need tracheotomy
16
than those whose infection is caused by HPV 6 a l o n e . However,
the final outcome was not affected by whether RRP was caused by
HPV 11 or HPV 6, and disease was just as likely to go into remis-
R
sion in those infected by HPV 11 as in those infected by HPV.
An additional risk factor may be infection by HPV 16 in the
larynx. Human papilloma virus 16 has been found in laryngeal car-
cinoma and in one case, we found HPV 16 in a laryngeal papil-
10
loma that later degenerated to squamous cell c a r c i n o m a .

VIRAL TRANSMISSION
It has been theorized for some time that juvenile disease is acquired
during birth by passage through an infected birth canal, and adult
disease is acquired by sexual contact. However, neither of these
theories has been well substantiated, and there is evidence for other
forms of transmission. For example, the database maintained by the
Recurrent Respiratory Papilloma Foundation reports the occur-
rence of RRP in 13 of 220 newborns delivered by cesarean section.
It is possible that the virus is present in amniotic fluid, and it is
also possible that the adult presentation is a latent infection
acquired perinatally rather than by sexual contact.
104 F.L. Rimmell

The majority of children with HPV infection are the firstborns


of young mothers (younger than age 25 at parturition). Additional
children born to the same mother and father seem to be immune
from infection. In a recent case, we diagnosed RRP in the fourth-
born child of a young mother; however, this child is the first born
to this mother from its father.
It is estimated that approximately 5 0 % of women in North
America have an HPV genital infection, and this proportion might
be even higher if specimens were analyzed using a PCR technique.
Currently the only condition in which cesarian section is recom-
mended to decrease the risk of perinatal newborn infection with
HPV is gross evidence of genital disease in the mother during preg-
nancy.

SURGICAL MANAGEMENT
ANESTHESIA AND AIRWAY MANAGEMENT
Many techniques have been proposed for management of the air-
way during surgery to treat RRP. The more common technique is
probably intubation with a laser-protected endotracheal tube. Our
preferred method is Venturi ventilation with a ventilating needle
attached to the laryngoscope placed above the larynx. Patients are
given propofol and fentanyl intravenously and lidocaine topically
over the laryngeal inlet and allowed to breath spontaneously. Once
the airway is secured, they are given a neuromuscular blocking
agent to maintain muscle paralysis throughout the remainder of the
procedure.
A difficult situation that may arise during use of the Venturi
technique is obstruction of the larynx, which can lead to pneumo-
thorax. In such cases we quickly debulk the larynx manually (us-
ing cup forceps) while the patient is apneic and then open the air-
way sufficiently to allow for ventilation.
Others avoid using Venturi ventilation during surgical manage-
ment of RRP because it is believed to lead to spread of the virus to
the distal trachea. We have used Venturi ventilation during opera-
tions to treat laryngeal or tracheal papillomas in more than 70 pa-
7, 1 0 , 1 6 1 7
tients, ' and distal tracheal spread is rare in our patients.
In addition, many of our patients have been referred to us after tra-
cheal spread occurred after treatment at institutions where Venturi
ventilation was never used.
Other techniques for ventilation during surgery to debulk pap-
illomas in the larynx and trachea include the apneic technique
with multiple intubations and transtracheal jet ventilation. In this
Management of Respiratory Papillomatosis 105

author's opinion, although the trauma of each individual intuba-


tion may be minor, the cumulative trauma of multiple intubations
is more likely to spread papillomatous disease distally than Ven-
turi ventilation.

EVALUATION AND STAGING


The most widely used system to stage RRP is that reported by
1B
Kashima. This system involves evaluation of the degree of
involvement at each of nine sites. One point is given for each ana-
tomical site harboring papillomata. Another point is added for any
site with more than one third involvement. Finally, an additional
point is scored when airway lumen encroachment is greater than
one third at any given site. A maximum score of 27 is possible,
and the stage of disease is categorized based on the total score as
mild (1 to 5 points), moderate (6 to 11 points), or severe (more than
12 points) (Table 1 ) . Other staging systems have been developed,
19
such as that described by Lusk et a l .

LASER SURGERY
The advent of laser surgery has not altered the goal of surgical man-
agement of RRP: to debulk as much as possible while maintaining
the airway and doing no harm.
The carbon dioxide laser greatly enhances the surgeon's abil-
ity to debulk disease. However, overzealous application of laser en-

TABLE 1.
18
The K a s h i m a Respiratory Papilloma Staging System

Location
Epiglottis 1 1 1
False vocal cord 1 1 1
Ventricle 1 1 1
True vocal cord 1 1 1
Subglottis 1 1 1
Tracheotomy site 1 1 1
Trachea 1 1 1
Carina 1 1 1
Mainstem bronchi 1 1 1

Total possible score = 27. Total score of 1-5 = mild; 6-11 = moderate;
> 1 2 = severe.
106 F.L. Rimmell

ergy can lead to significant scarring that can result in residual air-
way or vocal cord dysfunction, even after the disease goes into re-
20 21
m i s s i o n . ' In addition, a patient will not be cured of RRP disease
by vaporization of visible papillomata.
It is best to leave disease in the anterior and posterior commis-
sure, because most complications that occur after remission are re-
lated to damage and scar tissue in these areas. In an adult or older
child who has minimal disease and for whom preservation of voice
is more important than increasing airway diameter, we will care-
fully debulk the free edge of the vocal fold and the anterior com-
missure region, removing papillomata by hand, under the operat-
ing microscope.
Three other lasers are in common use for surgery: the argon
laser, neodymium yttrium-aluminum-garnet (Nd-YAG) laser, and
the potassium titanyl phosphate (KTP) laser. These lasers offer no
major advantages over the carbon dioxide laser in terms of achiev-
ing remission of RRP. However, energy from these lasers can be
transmitted by fiberoptic cable, which is an advantage in treating
disease in the distal airway. For example, the fiberoptic cable can
be passed alongside a Hopkins rod telescope or through the suc-
tion channel of a flexible bronchoscope for superior visualization
and control of disease in the distal trachea and bronchi of small
22
children.
Another surgical laser technique that has been studied for treat-
ment of RRP involves photodynamic therapy. Abramson et al.
found a statistically significant decrease in the rate of papilloma
23
growth after photodynamic t h e r a p y in a study in which they ad-
ministered 2.5 mg/kg of a dihematoporphyrin agent intravenously
48 to 72 hours before photoactivation using a tunable argon pump
dye laser emitting red light (630 nm) through a 4 0 0 m flexible fi-
ber. Duration of photoactivation varied from 100 to 200 seconds at
2
a light dose of 50 J / c m with no additional benefit found when this
2 2 4
dose was increased to 80 J / c m . Although the results are encour-
aging, there was no control group for comparison (each patient
served as his or her own control), and many of these patients might
have improved without treatment over the natural history of the
disease.
An additional problem with the method described by Abram-
son et al. is that argon pump dye lasers are expensive, not widely
available, and currently have few clinical uses. During the last 5
years, however, various pulse dye lasers have become relatively in-
expensive and more widely available. Often such lasers may be
found in the offices of local dermatologists and facial plastic sur-
geons. Reports in the dermatology literature indicate that use of
Management of Respiratory Papillomatosis 107

pulse dye lasers alone can lead to remission of cutaneous HPV, and
studies are underway in which these lasers are being used to treat
RRP in the larynx.

TRACHEOTOMY
Performing tracheotomy on a patient with laryngeal papillomato-
sis is frowned upon and thought to cause distal tracheal papillo-
matosis. However, from our experience, we have come to believe
that patients with tracheal papillomatosis have a more aggressive
form of the disease and thus require different management than the
17
majority of patients with R R P .
In our series of 35 children, 13 required tracheotomy, in six
cases as an emergency procedure to manage airway obstruction.
The more aggressive disease in these 13 patients was usually
1 6
caused by HPV l l . They presented to us at an earlier age (21.4
months vs. 52.3 months) and required more surgery before trache-
otomy (an average of 0.95 procedures per month vs. 0.62). Ten of
the 13 children have been decannulated, usually when the disease
went into remission, at an average age of 6 years and 4 months.
Distal tracheal disease developed in 2 patients who did not
undergo tracheotomy.
Our current recommendation is that if a child is presenting
more frequently than every 6 weeks for a procedure due to airway
obstruction, tracheotomy should be considered. Although papillo-
mas will grow around the tracheotomy site due to squamous meta-
plasia at the site, these lesions will typically disappear when the
disease goes into remission.

MEDICAL MANAGEMENT
A number of adjunctive medical therapies have been tried for pa-
tients with RRP. To date only interferon has been studied in large,
controlled clinical trials, and the benefits of this drug are still in
question.

INTERFERON
Interferons are polypeptides produced by cells in response to vari-
ous protein stimuli, particularly viral particles. Interferons are clas-
sified by cell of origin and type of inducer. Type 1 interferons are
induced by viruses and include leukocyte (alpha) and fibroblast
(beta) interferons; type 2 interferons include immune gamma in-
terferon, which is secreted by lymphocytes.
The first report of interferon therapy for RRP was published
in 1981 and showed improvement in two children with tracheal-
108 F.L. Rimmell

bronchial spread to whom an interferon inducer was adminis-


25
tered.
Two years later, McCabe and Clark reported some benefit from
administering human alpha-interferon to 19 patients in an uncon-
26
trolled study. Treatment doses of 3 million to 10 million units,
depending on the child's size, were administered three times a
week for 3 months; doses were reduced by one third every 3
months until a maintenance dose of one third the treatment dose
was reached, and this dose was administered for 1 year.
Five years later, Leventhal and Kashima reported benefits from
administering alpha-nl, a purified preparation of alpha-interferons
produced by virus stimulation of a human lymphoblastoid cell
line, to 66 patients who served as their own controls in a cross-
2 7 2 8
over study of surgery plus alpha-nl or surgery a l o n e . ' The dose
2
of alpha-nl was 5 M U / m daily for 28 days, followed by the same
dose thrice weekly for 5 months. When patients received alpha-nl
in addition to surgery they had a significant decrease in the amount
of physical disease present. Discontinuation of drug therapy
showed a significant rise in scores within 4 months. Mulooly et al.
29
also reported good results with alpha-interferon.
On the other hand, Healy, et al reported no long-term benefits
of administering human leukocyte interferon to 1 1 8 patients ran-
domly assigned to undergo surgery plus interferon or surgery alone
30 2
( c o n t r o l ) . Interferon dosages were 2 X 1 0 6 I U / m daily for 1 week,
and then three times a week for 12 months. Findings revealed a
significant decrease in the growth rate of papillomata in the first 6
months in patients receiving adjunct interferon therapy, becoming
nonsignificant in the second 6 months of the study. Laryngeal ob-
struction increased less in the interferon group than in the control
group during a 9-month follow-up period.
In this study, one of the reasons for lack of a statistically sig-
nificant difference between the control group and the interferon
group during follow-up is that the rate of papillomatous growth
slowed in the control group during the 12-month study, which il-
lustrates the difficulty of detecting any real difference in the results
of treatments when the natural history of the disease involves ex-
acerbations and remissions. The natural history of RRP probably
also accounts for the lack of response to interferon in two children
with more severe laryngotracheal disease who were given the drug
31
in uncontrolled fashion in one small case s t u d y and, in fact, in
all studies reported to date in the literature.
Intralesional injection of interferon has been tried for RRP, and
Heberhold and Walther reported excellent results in 11 patients
Management of Respiratory Papillomatosis 109

who received intralesional injections of alpha-2a-interferon after


32
laser surgery. However, all studies reported to date have been un-
controlled and limited to patients with laryngeal disease.
What are current recommendations for interferon use? If pa-
tients are being operated on every 2 months or less, then they
2
should receive alpha-nl interferon, 2 M U / m body surface area per
2
day or 4 M U / m every other day, for 6 months. If there is no re-
33
sponse at the end of this time, treatment should be discontinued.
We reserve the use of interferon for our most severely ill patients,
for whom we are contemplating tracheotomy or whose disease has
spread beyond the carina. Our goal is to reduce the number of le-
sions temporarily and prolong the period between operations. The
fact that there often appears to be some initial effect from interferon
supports the theory of immune regulation in lesion production.
However, our severely ill patients have not typically responded as
well to interferon as patients in reported studies.
A note of caution regarding the use of interferon: there can be
brisk rebound of lesional growth after withdrawal of the drug. Cli-
nicians are advised to read cited studies and other pertinent litera-
ture before initiating interferon therapy for RRP. Currently, new
studies are underway to evaluate a second generation of interferon
agents.

INDOL-3-CARBINOL
Indol-3-carbinol is a vitamin supplement. Initial reports of the re-
sults of administering this agent in uncontrolled fashion to patients
with RRP patients showed a substantial slowing in the visible
growth of lesions. Multi-institutional controlled studies are cur-
rently being carried out.
Although the exact mechanism by which indol-3-carbinol
might reduce papillomatous growth is unclear, the substance is
known to induce 2-hydroxylation of estradiol resulting in
2-methoxy-estrone. This effect on estrogen metabolism may be
related to the observation that RRP will typically go into remission
at about the time of puberty.
Alternatively, 16 hydroxylation of estradiol forms estriol,
which is thought to enhance papilloma proliferation. Newfield et
34
a l . demonstrated in tissue culture that 16 hydroxylation was sub-
stantial in the normal larynx, which is rich in estrogen receptors.
It was further demonstrated in culture that 2 hydroxylation
induced by indole-3-carbinol abrogates the proliferative effects of
34
estriol.
110 F.L. Rimmell

The recommended dosage of indol-3-carbinol for adults is 200


to 400 mg per day and for children weighing less than 20 kg it is
100 to 200 mg per day. The product can be obtained at many health
food stores. Although we are unaware of any adverse effects of us-
ing indol-3-carbinol, we leave the decision to take this substance
to the discretion of our patients and hope that the results of con-
trolled studies will soon be available.

ACYCLOVIR
A report of an uncontrolled study in three patients showed an im-
35
pressive response of RRP lesions to acyclovir. The first patient re-
ported on was a 5-year-old child whose lesions disappeared after
she received 300 mg per day of acyclovir intravenously for 5 days.
Two additional children received between 500 and 600 mg a day for
35
6 months with resolution of visible lesions in both c h i l d r e n .
The rationale for the use of acyclovir to treat RRP is that it pre-
vents replication of DNA viruses. However, acyclovir is a purine
nucleoside recognized by the enzyme thymidine kinase, which
converts it to a triphosphate form and incorporates it into replicat-
ing DNA where it causes breaks in the replication cycle. Because
HPV does not use acyclovir-sensitive thymidine kinase for viral
replication, there is no explanation at present for any effects acy-
clovir may have against disease due to HPV.
Morrison and Evans used acyclovir to treat four children with
31
R R P . The first child suffered from severe laryngotracheal disease
that failed to respond to 6 months of treatment with both acyclo-
vir (500 mg per day) and interferon. The second child, a 3-year-old
also with laryngotracheal disease, showed some decrease in the
number of lesions after 2 months of treatment with 500 mg per day
of acyclovir; however, the evaluations were subjective and the de-
crease in lesions could have been due to the variation in lesion bur-
den over the natural history of the disease. The other two children
in this series showed no response to acyclovir.
Endres studied the effects of acyclovir in six patients, two of
36
whom stopped taking interferon to begin acyclovir. They admin-
istered doses of 10 mg/kg five times a day for 10 days, then 10
mg/kg twice a day for 6 weeks. There were no control subjects.
18
Evaluation of change in disease grade using both the K a s h i m a and
19
L u s k scoring systems showed statistically significantly more im-
provement in the four patients who had not received interferon
first, probably because the two children withdrawn from interferon
had such a strong rebound in papillomatous disease after with-
drawal.
Management of Respiratory Papillomatosis 111

The studies of acyclovir just reviewed point out two major


problems in evaluating the effectiveness of medical therapy for RRP
from reported studies: the studies involve small numbers of
patients and no control group. A further problem with acyclovir is
the lack of any rationale for its effectiveness, based on current un-
derstanding of the drug's actions on viruses. Although acyclovir is
a relatively safe drug, we do not administer it to our patients with
HPV infection unless they have evidence of a coexisting herpes
8
simplex infection.

ISOTRETINOIN
Isotretinoin is a retinoid and therefore an analogue of vitamin A.
Retinoids inhibit the proliferation of both normal and neoplastic
cells. They can also modulate the differentiation of epithelial tis-
sue, including the human laryngeal keratinocyte. These actions
make it reasonable that isotretinoin would help to control RRP by
stabilizing squamous epithelium.
Reppucci et al. studied the effects of retinoic acid on epithe-
lial cells in culture infected by HPV and found that the epithelium
changed from squamous epithelium to columnar and that the con-
37
tent of HPV DNA decreased.
Alberts et al. treated five patients with doses of between 0.5
mg and 2.0 mg/kg per day for between 5 and 24 months; within 9
months of the start of therapy, two patients experienced complete
38
remission and one responded partially.
Bell enrolled six patients in a randomized study of high dose
2
isotretinoin (100 m g / m ) vs. no drug and noted no clinical
39
improvement in those receiving isotretinoin.
Lippman et al. treated three patients with severe resistant dis-
ease with a combination of interferon alpha-2a (Roferon) at a dose
of 3 X 106 U per day and isotretinoin at a dose of 1 mg/kg per day.
The combined therapy greatly increased the time until the next sur-
40
gery compared to interferon a l o n e .
When we prescribe isotretinoin for our patients we follow liver
enzymes closely. We have obtained mixed results with this drug
and possibly would have had similar results if the disease were
allowed to follow its natural history. The combination of interferon
and isotretinoin seems promising; multidrug therapy with agents
that attack the virus in various ways may be necessary to keep rep-
lication of the virus in check.

METHOTREXATE
Avidano and Singleton reported treating three patients with meth-
41
otrexate with good results. Two patients received an oral dose of
112 F.L. Rimmell

1 mg/kg per week and one patient received one dose intravenously
followed by leucovorin rescue every other week. Although the
amount of disease was decreased, no patient achieved a complete
remission.
We have used methotrexate to treat a few of our patients with
severe disease, with mixed results.

RIBAVIRIN
Ribavirin is a synthetic nucleoside with low toxicity that is active
in the inhibition of both viral DNA and RNA synthesis. Ostrow, et
al studied rabbits infected by the Shope papilloma virus and found
a significant, dose-dependent reduction in wart production in those
42 4
receiving ribavirin. In an initial study in four patients, ' two
adults had complete remission and one adult and one infant had a
partial response to a ribavirin loading dose of 23 mg/kg adminis-
tered intravenously, followed by 23 mg/kg per day taken orally in
four divided doses. The goal was to achieve a blood level of 20 to
30 umiol/L of ribavirin. From these preliminary data, a full random-
ized blinded study was started and is near completion. Results
from the study at the University of Minnesota are encouraging;
however, the Shope papilloma virus is not the same as HPV, so the
effects of ribavirin for RRP remain in question.

DISEASE COMPLICATIONS
Pulmonary metastasis of HPV is one of the most feared complica-
tions of RRP. Metastasis occurs during the active stage of HPV rep-
lication and currently may be diagnosed by changes on the chest
x-ray and confirmed by finding lesions on a computed tomography
44
(CT) scan of the c h e s t . These lesions may be either solid or cavi-
tated, single or multiple (Figure 1 ) .
Metastasis of RRP is thought to result from surgical manipula-
tions in the airway during Venturi ventilation, jet ventilation, or
tracheotomy. However, we believe the metastasis is more likely due
to pathogenic spread of a more virulent form of the virus, prob-
ably in combination with decreased host immune response to the
HPV infection.
Pulmonary metastasis is difficult to manage and in most cases
results in death of the patient. Often, especially in patients whose
disease has persisted from early childhood, metastatic papillomas
45
contain evidence of squamous cell c a r c i n o m a . It is therefore our
policy to take an aggressive approach once the diagnosis of pul-
monary spread is made. If the disease is resectable, i.e., only a few
lesions are found, we refer the patient to a cardiothoracic surgeon
Management of Respiratory Papillomatosis 113

FIGURE 1.
Computed tomography (axial plane) scan through the chest of a 3-year-
old girl with metastasis of recurrent respiratory papillomatosis to both dis-
tal lung fields. Metastatic lesions appear as multiple high-density solid
masses (white arrow).

for removal. A recent report describes removal of three pulmonary


46
carcinoma lesions due to R R P .
For patients with multiple nodules, we recently began to use a
combination of interferon, ribavirin, and methotrexate to control
the virus and induce remission. Follow-up periods are as yet too
short to determine the effects of this regimen.

TREATMENT COMPLICATIONS
Many complications can arise as the result of surgical or nonsur-
gical treatment of patients with RRP, including damage due to a
laser fire during surgery, laryngeal web, laryngeal stenosis, subglot-
tic stenosis, posterior glottic stenosis, and pneumothorax.
Webs and stenosis are not uncommon problems in the treat-
ment of patients with RRP. They are usually due to aggressive sur-
gical technique but may also represent residual effects of the dis-
ease process that appear during remission. It has been our policy
114 F.L. Rimmell

not to consider repair of a web or stenosis until the disease has


remained in remission for 12 continuous months. The virus, how-
ever, is always present, even in remission, and repair of a glottic
web or stenosis may result in a flare-up of disease.

SUMMARY
Overall, the treatment of HPV infection has changed little over the
last 50 years. The fundamentals of treatment continue to be debulk-
ing grossly visible lesions, maintaining an adequate airway, and
managing symptoms until remission occurs. Significant progress
has been made, however, in our ability to maintain an airway.
We have also gained in our understanding of virus behavior.
We now know that once the squamous epithelium of the airway is
infected by HPV, it is infected for life. Although infection is
chronic, changes in virus activity lead to periods of remission.
Human papilloma virus spreads by squamous metaplasia down
the airway. Laryngeal infection can be controlled by carbon diox-
ide laser surgery, and distal visible lesions can be removed with a
fiberoptic laser in a flexible bronchoscope. Patients may be offered
a trial of one or more adjunctive medications to induce remission
or control aggressive disease. Interferon has been the most exten-
sively studied, but its effectiveness is still in question. Interferon
should be reserved for those who require surgery at less than
8-week intervals or who have aggressive disease. To date, acyclo-
vir, indol-3-carbinol, methotrexate, cis-retinoic acid, and ribavirin
have all failed to show any great benefit for RRP. The cure for this
disease may involve multidrug therapy with a number of antiviral
agents; it is still over the horizon.

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of pulmonary carcinoma secondary to recurrent respiratory papillo-
matosis. Ann Thorac Surg 60:1806-1807, 1995.
CHAPTER 7
Carcinoma of the
Nasopharynx
William Ignace Wei, M.S., F.R.C.S.E., D.L.O.
Professor of Otorhinolaryngology, Division of Head & Neck/ENT/Plastic
Surgery, Department of Surgery, The University of Hong Kong, Queen
Mary Hospital, Hong Kong

N asopharyngeal carcinoma (NPC) is the most frequent malig-


nancy of the nasopharynx; histologically, it is nonglandular,
nonlymphomatous, squamous cell carcinoma. It is unusual in that
its incidence varies widely among ethnic groups. It is a common
malignant disease affecting Southern Chinese people, especially
1
the Cantonese, i.e., people from the Kwangtung Province. In
Hong Kong, it is the third most common cancer in males and the
fifth in female patients with an incidence of 27.5 and 1 1 . 2 per
2
1 0 0 , 0 0 0 , respectively. Despite population movements in the past
century, the incidence of NPC has remained high among ethnic
3
Chinese.
The high incidence in the southeastern Chinese and their de-
scendants suggests that genetic abnormalities may be etiologic fac-
tors. Other possible agents are the consumption of salt fish and in-
fection with the Epstein-Barr virus (EBV). It has been shown that
the frequent consumption of large quantities of salt fish before the
age of 10 years is associated with an increased risk of developing
4
NPC. This may be related to nitrosamine compounds contained
5
in salt fish. The geometric mean titer of antibodies, particularly
the IgA class, in response to Epstein-Barr viral capsid antigen in
patients suffering from NPC was found to be higher than in con-
trol groups of patients with other head and neck cancers and also
6 7
normal s u b j e c t s . ' The E B V genome and EBV-associated antigens
B 9
have consistently been found in NPC cells, ' and EBV receptors
10
were reported to be present on NPC c e l l s . However, the causal
relationship between the virus and NPC has not been substantiated.
This is because EBV infection is common all over the world,
whereas the incidence of NPC has a marked geographical variation.
9
Advances in Otolaryngology-Head and Neck Surgery , vol. 12
e
1 9 9 8 , Mosby, Inc.
120 W.I. Wei

The etiology of NPC, as in other malignancies, is probably mul-


tifactorial. The factors that may be involved are heredity, carcino-
gens, and viral infection.

DIAGNOSIS
The most common symptom at initial diagnosis is enlarged cervi-
cal lymph nodes. Other common nasal symptoms are epistaxis, na-
sal obstruction, or blood-stained postnasal drip. Otologic symp-
toms such as otalgia, tinnitus, and deafness are also frequently evi-
dent. Less often, the patient's chief complaint is of headache, or
symptoms and signs of cranial nerve palsies are present.
Examination of the nasopharynx is difficult with the postnaso-
pharyngeal mirror. Endoscopes, either flexible or rigid, can be used
for thorough examination of the nasopharynx, and biopsies of sus-
picious areas in the nasopharynx may be carried out under direct
vision. The extent of tumor on the mucosal surface can be ascer-
tained by endoscopic examination, whereas the extent of deep in-
filtration may only be determined by radiologic examination such
as computed tomography (CT) or magnetic resonance imaging
(MRI).

CT
Plain X rays of the skull base and conventional tomography for the
examination of the nasopharynx for assessment of bony erosion
around the nasopharynx have now been replaced by CT. When ad-
justed to visualize osseus outlines, CT reveals unequivocal evi-
dence as to whether there is bony erosion. Computed tomography
with contrast gives superior images of soft tissues and provides in-
formation on the deep extension of the primary tumor and its lat-
eral extent. Enlarged paranasopharyngeal lymph nodes more than
1 cm in diameter may also be detected. A CT examination of the
neck can detect enlarged cervical lymph nodes and provide infor-
mation concerning the lymphatic spread of the disease.
The exact extension of the tumor is important in the staging of
11
the disease and in the planning of radiotherapy. Computed to-
mography is now considered essential in the assessment of patients
who have NPC.

MRI
Computed tomography can reveal the lateral and deep extension
of a tumor; however, differentiation of tumor from the surround-
ing mucosal and submucosal inflammation of the nasal cavity and
sinuses is sometimes not possible. Assessment of the vertical ex-
Carcinoma of the Nasopharynx 121

tent of the tumor by direct coronal imaging at CT is necessary, with


patients being requested to extend the neck during the examina-
tion. Elderly patients and those with cervical pathology may not
be able to comply with requirements. An MRI with gadolinium en-
hancement can provide additional information to enable identifi-
12
cation of tumor from inflamed t i s s u e . During MRI, the patient has
to remain in the supine position only, and images in three dimen-
sions can be obtained. In addition to the two views provided by
CT, MRI's sagittal images give information regarding vertical tumor
extent that is useful in the planning of therapy. The limitations of
MRI are that it does not yield information on bony involvement by
tumor, and it cannot be done for claustrophobic patients or those
with metallic implants.
Magnetic resonance imaging provides findings that comple-
ment CT examination but cannot show bony erosions. It is usually
only performed when considered essential to allow better planning
of therapy.

TREATMENT
RADIOTHERAPY
Because NPC is radiosensitive, the primary treatment modality is
external radiotherapy. The irradiation field covers the tumor in the
nasopharynx with its infiltration of surrounding tissue as deter-
mined by CT or MRI and enlarged metastatic lymph nodes in the
neck. The usual radiation dose delivered to the nasopharynx ranges
from 66 to 70 Gy and approximately 60 Gy to the neck. This dos-
age is usually given in 1.8 to 2 . 0 Gy daily fractions through two
13
lateral opposing fields with or without an anterior field. Because
there is a high propensity for metastasis of NPC to cervical lymph
nodes, the neck is always included in the irradiation field even
though there may be no clinically positive neck nodes. With the
delivery of 50 Gy to the clinically negative neck, improvement in
14
survival has been demonstrated. Current radiation treatment
gives an overall survival of 5 0 % in patients with NPC. The 5-year
survival rates for early stages range from 5 0 % to 9 0 % and that of
1 5 > 16
stages III and IV from 7% to 6 0 % .
In recent years, improved tumor control has been possible with
the modification of radiotherapy treatment plans. As an alternative
to conventional fractionation, accelerated hyperfractionation of ra-
17
diation dosage was shown to be beneficial. The development of
conformal radiation treatment after accurate delineation of the pri-
mary tumor by CT and MRI has also contributed to better tumor
122 W.I. Wei

control, while at the same time minimizing the irradiation damage


18
to normal t i s s u e s .
As the nasopharynx is in the center of the head, radiation de-
livered to the nasopharynx will invariably affect surrounding nor-
mal structures. Early complications include mucositis, swelling of
salivary glands, and altered sensation of taste. Some late compli-
cations may prove more troublesome. These include neuritis of the
cranial nerves IX—XII, decreased production of saliva, fibrosis of
pterygoid muscles leading to trismus, and panhypopituitarism.
Most morbidity is unavoidable and is part of the sequelae of the
radiotherapy. Recently, shielding of the pituitary gland was per-
formed during radiotherapy; this was found to be effective in re-
ducing neuroendocrine complications without compromising
19
therapeutic o u t c o m e . Other significant long-term complications
of radiation include sensorineural hearing loss (SNHL), temporal
lobe necrosis and, very rarely, radiation-induced sarcoma of the
maxilla.
A prospective study of SNHL in 132 patients who received
radical dosage radiation treatment for NPC documented that at a
median follow-up of 30 months, SNHL was transient in 1 9 % of pa-
tients and persistent in 2 2 % . The degree of hearing loss was greater
in the high-frequency range.
Multivariate analysis identified female sex, age 50 years, and
the development of postradiation serous otitis media as significant
20
factors associated with persistent S N H L .
A more serious complication of radiotherapy is temporal lobe
necrosis. Mild symptoms can be controlled with steroids and con-
servative treatment. Extensive necrosis with severe symptoms may
21
require surgical intervention, although outcome remains poor.
The rare occurrence of radiation-induced sarcoma of the maxilla
or neck tissue, however, might be salvaged with surgical extirpa-
22
tion.

SURGERY
In the management of NPC, surgery is reserved for the treatment of
recurrent or residual disease after external radiotherapy. Surgical
salvage may be considered when recurrent or residual tumor is ei-
ther in the nasopharynx or in the neck. When tumor is present both
at the primary site and in the cervical region, extensive disease is
probable and at present, surgery with curative intent should be con-
sidered with caution.
Carcinoma of the Nasopharynx 123

CERVICAL LYMPH NODE METASTASES


The incidence of localized residual or recurrent NPC in cervical
lymph nodes after external radical radiotherapy with or without
2 3 2 4
chemotherapy has been reported to range from 3% to 1 0 % . '
Further external radiotherapy can be given, and the salvage dosage
has to exceed that of the initial treatment. Despite the expected
higher complication rate associated with a second course of radio-
therapy, local tumor control in those nodes smaller than 4 cm was
achieved in only 5 1 % , and the overall survival rate of this group of
2 5
patients was 1 9 . 7 % . Radical neck dissection carried out as a sal-
vage procedure has been shown to control disease in the neck
2 6
nodes in 6 6 % of patients, with a 5-year actuarial survival of 3 8 % .
Cervical lymph node involvement by NPC is usually more ex-
tensive than is clinically evident. This was confirmed by step-serial
27
sectioning study of 43 radical neck dissection s p e c i m e n s . In 7 3 %
of patients, there were more tumor-bearing lymph nodes detected
pathologically than was clinically apparent or identified at the time
of surgery (Figure 1). In 7 0 % of patients, lymph nodes examined
showed extracapsular spread of tumor; in 3 5 % , isolated clusters
of tumor were seen in the soft tissues of the neck. When lymph
nodes around the spinal accessory nerve were examined, 2 7 . 5 %
harbored tumor in lymph nodes lying close to the nerve, either ex-
hibiting perineural involvement or infiltrating the fibrous tissue
that encased the nerve.
Based on pathologic findings of the extensive nature of neck
disease in NPC, excision of clinically enlarged nodes alone is in-
adequate, because tumor-bearing lymph nodes could be left in situ.

FIGURE 1.
Histologic slide of neck dissection specimen showing more tumor-bearing
lymph nodes pathologically (arrows) than are clinically evident (hema-
toxylin and eosin x 4 0 ) .
124 W.I. Wei

FIGURE 2.
Left, hollow nylon tubes placed accurately in the tumor bed after radical neck
dissection. Right, deltopectoral flap was used for resurfacing, covering the
irridium wires placed in the nylon tubes for brachytherapy.

Even a modified radical neck dissection is considered insufficient,


as tumor-bearing lymph nodes are in close proximity to various
structures such as the sternomastoid muscle, internal jugular vein,
and accessory nerve. Radical neck dissection, removing all tumor-
bearing tissue in the neck, is advocated for salvage.
When tumor-bearing lymph nodes extend to involve the skin,
this overlying skin should be removed to achieve macroscopic
clearance. The defect may be adequately covered with a regional
flap such as the deltopectoral flap. If tumor in the lymph nodes
spreads outside the capsule to infiltrate the muscular floor of the
neck or adventitia of the carotid vessels, then surgical macroscopic
clearance is still possible. The margin of resection, however, would
be minimal. To improve prospects of salvage, hollow nylon tubes
may be positioned in the tumor bed accurately at the time of radi-
cal neck dissection and postoperative brachytherapy instituted
by insertion of iridium wires through the nylon tubes. As overly-
ing skin is irradiated during the initial treatment phase, it may
not tolerate brachytherapy. When postoperative brachytherapy is
planned, overlying skin is removed and replaced with pedicle
flaps, such as deltopectoral or pectoralis major myocutaneous flap
that have not been irradiated (Figure 2 ) .
This approach was undertaken in 14 patients in the Head and
Neck Division at the Department of Surgery, The University of
Carcinoma of the Nasopharynx 125

Hong Kong, at Queen Mary Hospital. Pathologic specimens in all


patients showed a minimal tumor resection margin. All patients
tolerated the procedures well, with no mortality and minimal mor-
bidity. At median follow-up of 12 months, the local tumor control
rate was 7 7 % and actuarial survival was 5 5 % . Our surgical strat-
egy is thus considered useful for selected NPC patients who suffer
from extensive regional disease.

PRIMARY NASOPHARYNGEAL TUMOR


BRACHYTHERAPY
Although NPC is radiosensitive, in some patients the tumor per-
sists or recurs in the nasopharynx despite radical doses of external
28
radiotherapy. To eradicate the disease, a further course of exter-
nal radiation at a dosage greater than the original therapeutic dose
is required for a favorable outcome. The resulting radiation effects
on normal surrounding tissues are not without morbidity. Late
complications related to neuroendocrine injury, poor nonverbal
memory recall, severe trismus, and even temporal lobe necrosis
may occur.
To circumvent these problems, brachytherapy may be used to
treat small persistent or recurrent tumors in the nasopharynx.
Brachytherapy using cesium intubation may not achieve the de-
sired dosimetry because of limitations of nasopharyngeal anatomy
and tumor location. We have used the split palate approach to in-
1 9 8
sert radioactive gold grains ( A u ) into the tumor under direct vi-
30
sion to act as the brachytherapy s o u r c e . In 43 patients in Hong
Kong, the control of tumor in the nasopharynx at 5 years was 8 0 % .
These were selected patients with recurrent or persistent tumor less
than 1 cm in diameter, localized in the nasopharynx, with no dis-
31
ease elsewhere.

SURGICAL RESECTION
Recurrent or persistent tumor in the nasopharynx may be too ex-
tensive locally for gold grain implantation to be useful. Occasion-
ally, the tumor may have extended into the paranasopharyngeal
space, and brachytherapy is not applicable. In these circumstances
surgical resection offers the only option for salvage.
Because the nasopharynx is located in the center of the head,
32
it is not easy to gain exposure to allow oncologic resection. Vari-
ous transantral and transnasal approaches to the nasopharynx en-
able visualization of the tumor but are inadequate for an oncologic
33
surgical procedure to be carried out. Whereas the inferior
approach through the palate can expose the entire tumor to allow
126 W.I. Wei

the insertion of radioactive gold grains, it does not permit exten-


sive resection of a large tumor with an adequate margin. This is
particularly true if the tumor has extended into the paranasopha-
ryngeal space.
Wider exposure of the nasopharynx may be achieved with
34
downward fracture of the entire hard palate. The transcervical
combined with transpalatal approach provides greater access to the
nasopharynx for tumor extirpation. The ability to control the ca-
35
rotid artery in the neck is certainly an added advantage. Trans-
cervical and transmandibular approaches expose the lower naso-
30
pharynx further for resection of a low-lying tumor.
Recurrent or persistent nasopharyngeal carcinoma is frequently
located in the fossa of Rosenmiiller, situated in the upper part of
the nasopharynx. Thus, adequate exposure of this region is impor-
tant. The paranasopharyngeal space located lateral to the eusta-
chian tube also has to be exposed before radical resection can be
performed. Paranasopharyngeal lymph node enlargement is often
part of the clinical picture and direct tumor extension to this re-
gion is not uncommon. A technique that gains access to the upper
part of the nasopharynx, the adjacent skull base, and the parana-
sopharyngeal space is essential for an oncologic resection to be car-
ried out. We have used the anterolateral approach to the nasophar-
ynx for resection of recurrent or residual tumor in the nasophar-
ynx after radiotherapy. After appropriate osteotomies, the maxilla
attached to the anterior cheek flap can be turned laterally as one
osteocutaneous complex facilitating wide exposure of the whole
nasopharynx, including the eustachian tube orifice and the para-
37
nasopharyngeal a r e a . (Figure 3). Tumors in this region can be re-
38
sected with adequate deep and surrounding margins. (Figure 4).
After resection, the maxilla attached to the anterior cheek flap, from
which it obtains its blood supply, can be swung back to its origi-
nal position and fixed to the facial skeleton with miniplates.
Between 1989 and 1997, at The University of Hong Kong, we
have used this maxillary swing approach for resection of recurrent
or residual primary NPC after radiotherapy in a total of 48 patients.
Curative resection was achieved in 43 of them. All patients sur-
vived and were followed up from 6 to 90 months (median 28
months). Every patient had some trismus soon after surgery, but
this usually improved with time and passive stretching. Palatal fis-
tulae developed in nine patients and this was managed conserva-
tively with a dental plate. Two patients developed a sinus tract in
the facial wound related to an underlying infected miniplate with
healing after removal of the plate. Eight patients developed recur-
Carcinoma of the Nasopharynx 127

rence of local tumor, three were found to have regional recurrence,


and 32 were free of disease. The local tumor control rate was 4 3 %
at 5 years, and the 5-year actuarial survival rate was 5 2 % .
Wide exposure of the nasopharynx is essential for an oncologic
resection of persistent or recurrent tumor localized to the nasophar-
ynx. This approach is supported by pathologic studies undertaken

FIGURE 3.
Schematic CT. Upper, planned osteotomies of the maxilla (dotted line) and
posterior part of nasal septum. Lower, the maxilla is swung laterally while
remaining attached to the anterior cheek flap. The posterior part of the sep-
tum is removed to gain exposure.
128 W.I. Wei

FIGURE 4.
Nasopharyngectomy specimen delivered en bloc. Eustachian tube marked
by plastic tube (arrow).

for nasopharyngectomy specimens. After delivery, the specimen is


stretched and pinned onto a foam board. The whole specimen is
then immersed in formaldehyde for fixation. Subsequently, step-
serial whole-organ sectioning is carried out at 5-mm intervals. His-
tologic sections stained with hematoxylin and eosin were exam-
ined to determine the pathologic behavior of the tumor. Nineteen
specimens were evaluated: 13 comprised only the nasopharynx,
whereas six also included paranasopharyngeal tissue. The median
number of sections carried out for each specimen was six, ranging
from 4 to 12 with a total of 123 histologic sections.
Although macroscopically the tumor may appear localized, on
histologic examination there was a tendency of the tumor to have
infiltrated beyond the mucosa. In 17 of the 19 specimens, tumor
was found to extend into the submucosal region with isolated clus-
ters of tumor cells. The distance between the edge of the macro-
scopic tumor and the furthest tumor island measured in the 19
Carcinoma of the Nasopharynx 129

specimens ranged from 5 mm to 24 mm, median 15 mm. In 18


specimens, tumor was found to be located close to the cartilage of
the eustachian tube crura (Figure 5). Of the six specimens that in-
cluded paranasopharyngeal tissue in the resection, tumor aggre-
gates were present in four. Tumor was present in the form of sheets
or islands of tumor clusters, the paranasopharyngeal tissue not be-
ing completely replaced by tumor.
Persistent or recurrent primary NPC after radiotherapy exhib-
its wide local extension. Excision of the tumor with an adequate

FIGURE 5.
Histologic slide of nasopharyngeal carcinoma. Upper, tumor (T) encroach-
ing onto the eustachian tube crura (arrow) (hematoxylin & eosin X 4 0 ) .
Lower, high-power view showing tumor cells close to the crural cartilage
(hematoxylin & eosin X 1 8 0 ) .
130 W.I. Wei

mucosal margin including the cartilaginous portion of the eusta-


chian tube is mandatory for successful salvage. Paranasopharyn-
geal tissues should be included in the resection whenever tumor
involvement is suspected. T h e anterolateral approach to the naso-
pharynx provides adequate exposure required for an oncologic re-
section. Associated morbidity is low, and this approach is recom-
mended for resection of persistent or recurrent primary NPC after
radiotherapy.

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14. Lee AW, Sham JS, Poon YF, et al: Treatment of stage I nasopharyngeal
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3 6 . Morton RP, Liavaag PG, McLean M, et al: Transcervico-mandibulo-
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37. Wei WI, Lam KH, Sham JST: New approach to the nasopharynx: The
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tion of tumors in and around the nasopharynx. Arch Otolaryngol Head
Neck Surg 1 2 1 : 6 3 8 - 6 4 2 , 1995.
CHAPTER 8
The Use of Biological
Therapy in Cancer of the
Head and Neck
Jeffrey N. Myers, M.D., Ph.D.
Assistant Professor of Head and Neck Surgery, T h e University of Texas
M.D. Anderson Cancer Center, Houston, Texas

T he rapid progress made in molecular biology and immunol-


ogy during the past several decades is finally being "trans-
lated" into technologic advances that are being applied in the
treatment of human illnesses. Better understanding of the molecu-
lar and cellular pathogenesis of neoplastic diseases has allowed a
more rational approach to the treatment of human cancer, in
which specific molecules important in the development or main-
tenance of the malignant phenotype are targeted for treatment.
Growth factors and their receptors, genes encoding proteins
important for mediating programmed cell death, and cells and
molecules important in regulating the antitumor immune re-
sponse are some of the targets for novel forms of biological
therapy for cancer. Research in these areas has resulted in
exciting preclinical data that have led to the inclusion of patients
with head and neck cancer in clinical trials of various biological
therapeutic strategies.
In this chapter, a brief review of the molecular alterations
that appear to be important for the development of head and
neck cancers is presented. It is followed by a discussion of
several different biological treatment modalities, including gene
therapy, antibody-mediated therapies, and immunotherapy. A
general background discussion of each of these treatment
strategies will precede a summary of current investigations in
each of these areas as they pertain to head and neck neo-
plasms.

Advances in Otoknyngology-Head and Neck Surgery*, vol. 12


'1998, Mosby, Inc. 133
134 J.N. Myers

TUMOR EVOLUTION AND MULTISTEP MODELS


OF CARCINOGENESIS
Current models of tumor development and progression are based
on the theory of natural selection. This theory states that cancer
cells that develop strategies to survive a hostile host environment
and that use host resources to grow and proliferate indefinitely will
have a survival advantage. As our understanding of the molecular
mechanisms of a variety of normal cellular processes increases, we
can see how "clever" cancer cells can exploit these mechanisms to
gain a selective growth advantage over other cancer cells.
In the tumor evolution model, a series of molecular events oc-
curs within a normal cell, transforming it to a neoplastic pheno-
type and providing the cell with a selective growth advantage over
1
neighboring c e l l s . As this cell proliferates, mutant progeny arise
as a result of genomic instability. Most of the offspring die owing
to immunologic selection, apoptosis, or metabolic derangement,
and a dominant cell expands clonally. With subsequent cell divi-
sions, new clones result that have acquired additional characteris-
tics that enable the tumor cell to continue to expand and spread
within the host.
The specific molecular events involved in a cell's evolution to
the malignant state have been elucidated through cytogenetic and
2
molecular genetic studies in colon cancer. These studies have
shown that tumors arise as a result of multiple accumulated ge-
netic alterations, some of which are inherited through the germ-
line, and the remainder of which result from repeated exposure to
DNA-damaging molecules in tobacco and alcohol.' It is thought
that through quantitative and qualitative alterations of genes im-
portant for the regulation of cellular growth and cell death, the nor-
mally exquisite control of cellular proliferation and cell death is
lost. Cells become immortalized, and their growth becomes un-
checked, leading to tumor formation. Additional molecular events
make tumors more aggressive in terms of invasion and metastasis.
The specific molecular events that lead to carcinogenesis in
mucosal sites in the head and neck are just beginning to be iden-
tified through cytogenetic studies as well as microsatellite and loss-
3
of-heterozygosity molecular genetic analysis. The cascade of mo-
lecular events has been assembled into an ordered series of events
that are believed to be important in the development of squamous
4
cell carcinomas. Alterations at loci at chromosomal regions 9p21
and 3 p l 4 are believed to be important early alterations involved
4, 5
in the development of dysplasia. Inactivation of the p53 protein
Biological Therapy in Cancer of the Head and Neck 135

is an event that tends to occur relatively late in tumor progression,


6
which also occurs frequently in squamous cell cancers. Gene am-
plification or overexpression of oncogene products or cell-cycle
regulatory molecules encoded at l l q l 3 is also thought to have a
7
role in disease progression as are other chromosomal events.
The occurrence of tumors in younger patients without a his-
tory of exposure to tobacco or alcohol supports the concept that
inherited germline defects play a role in the pathogenesis of oral
cavity squamous cell tumors, although the specific molecular al-
8-10
terations in these cases have not been clearly d e f i n e d . The de-
tection of human papilloma virus DNA in tongue tumor specimens
suggests that viral proteins known to interact with molecules im-
portant for the regulation of cell proliferation may also contribute
11,12
to tumor d e v e l o p m e n t .
As our understanding of the molecular and cellular defects that
lend tumor cells a survival advantage improves, we are better able
to identify potential targets for biological therapy and to apply
novel strategies to the preclinical study and clinical treatment of
head and neck cancers.
Current avenues of preclinical research, as well as clinical
studies evaluating the efficacy of biological strategies for the treat-
ment of head and neck cancer, including gene replacement strate-
gies, antibody directed therapies, and immunologic approaches,
are discussed in the following pages.

GENE THERAPY FOR CANCER OF THE HEAD AND NECK


BACKGROUND
The idea that treatment of human disease through the replacement
of defective genes might be possible arose shortly after the deter-
mination of the tertiary structure of DNA and the isolation of en-
zymes important for the replication, cutting, and splicing of DNA
fragments. However, it was not until this decade that the promise
of gene therapy began to be realized in preclinical investigations
and, more recently, clinical trials. The application of gene therapy
to cancer has a number of appealing aspects, particularly in those
tumors in which specific genetic defects have been shown to be
important and for which other, more conventional modalities have
been largely unsuccessful.
Many techniques have been developed for delivering genes to
the tumor or to the tumor-bearing host and a number of strategies
13
for using gene transfer technology are currently being evaluated.
A brief history of the development of gene therapy is followed
by a discussion of some available methods for gene delivery. Fi-
136 J.N. Myers

nally, some of the strategies for using gene therapy for the treat-
ment of neoplastic diseases will be addressed.

HISTORY
The ability to stably transfer or transfect DNA fragments into eu-
karyotic cells growing in vitro in tissue culture and to demonstrate
the expression of the transferred genes in the recipient cells
evolved as a research tool. It has led to tremendous advances in
identifying proteins important for the regulation of cell growth.
Subsequently, investigators have tried to adapt this technology to
the treatment of diseases in vivo. However, many issues needed to
be resolved to make this leap.
A group of scientists working at the National Institutes of
Health in the late 1980s and early 1990s were the first investiga-
tors to treat a patient using gene transfer methodology. In Septem-
ber of 1 9 9 0 , Drs. Michael Blaese, William French Anderson, and
Steven Rosenberg carried out the retrovirally mediated replace-
ment of the adenosine deaminase gene, the specific defect in a com-
bined immunodeficiency disorder known as adenosine deaminase
14
deficiency, in a patient with this disease. These same investiga-
tors were the first to use gene therapy to treat human cancers. They
initially treated two melanoma patients using the ex vivo admin-
istration of the gene encoding tumor necrosis factor (TNF) to the
patients' lymphocytes, followed by readministration of the lym-
phocytes to target the patients' cancer.
The use of gene therapy in these patients paved the way, in
terms of technology and overcoming ethical and regulatory issues,
for further developments in this area to take place.

METHODS OF GENE DELIVERY


Several methods have been developed for in vivo gene transfer, and
each method has strengths as well as shortcomings. The require-
ments for successful gene transfer include: (1) entry or uptake of
the DNA encoding the protein of interest into the target cell; (2)
replication of the transfected gene; (3) transcription and translation
of the gene of interest at suitable levels; (4) proper posttranslational
modifications of the resultant gene product; and (5) correct subcel-
15-15
lular localization or secretion of the gene p r o d u c t .
The major categories of gene delivery include physical or
15
chemical methods, and virally mediated gene transduction. This
last method takes advantage of the host cellular mechanisms that
viruses have exploited to gain entry into cells, take over the host
Biological Therapy in Cancer of the Head and Neck 137

cells' replicative functions, and produce proteins required for vi-


ral propagation. Both DNA and RNA viruses have been used as vec-
tors for this purpose. The major viral systems currently under scru-
tiny for their efficacy and safety as gene delivery systems in hu-
mans will be discussed in the following sections.

Retroviruses
Retroviruses were the first viruses used for the transduction of
genes into the cells of higher organisms, and their biology has been
1 1
extensively characterized and optimized for this purpose. ' Retro-
viruses are RNA viruses that attach to cells and deliver their ge-
nome to the host, where it becomes "reverse transcribed," yielding
a double-stranded DNA intermediate known as a proviral genome.
The proviral genome can in turn become integrated into the host
chromosome, which enables the virus' genetic material to be effi-
ciently replicated as the cell proliferates. This stable integration of
the foreign gene into the host genome allows for long-term expres-
sion, which may be particularly beneficial in the treatment of cer-
tain chronic conditions.
To prevent these viruses from infecting new target cells, sev-
eral genes encoding proteins essential for production of the virus
are deleted. The result is that once the virus enters the cell, its ge-
nome can be replicated and the desired gene of interest can be ex-
pressed, but the virus cannot produce future generations of retro-
1(>
virus. Retroviruses have been proven to be safe in preclinical
studies and in several human clinical trials. However, the random
nature of viral DNA integration means there is a risk of viral inte-
gration that would disrupt the qualitative or quantitative expres-
sion of proteins important for maintaining cellular homeostasis or
preventing oncogenesis thereby promoting rather than inhibiting
tumor progression.
Other problems that have been encountered with practical
evaluation of retroviral vectors is their inherently low infectivity
rate and the loss of viral expression over time. Recent research
into retroviruses has focused on targeting specific receptors on the
recipient cells of interest to increase the infectivity of these
viruses and to improve the therapeutic ratio of virally mediated
17
therapies.
Another area that remains to be resolved is the optimization of
delivering a replication-defective retrovirus to an entire tumor. Be-
cause tumors are believed to arise from a single cell, it is believed
that the most successful strategies will be those that can target all
of the cells within a tumor. Because retroviral vectors used in gene
138 J.N. Myers

therapy are replication defective, delivery of the gene to all areas


of a tumor (or tumors in the case of metastatic disease) remains a
problem. Local injection has been used primarily, but ex vivo meth-
ods and ligand- or antibody-mediated targeting schemes have been
devised and are being evaluated for efficacy.
One final limitation of retroviruses is the size of the gene that
can be inserted for expression in host cells. Genes up to 8 kb in
size can be inserted in retroviral vectors, but the use of these vi-
ruses for larger genes is limited.

Adenoviruses
Adenoviruses, double-stranded DNA viruses, have become another
appealing system for gene delivery. Vectors based on the A d 5 vi-
rus have been particularly useful because of their ability to effi-
ciently transduce a wide variety of cell types, independent of their
13 15
mitotic s t a t u s . "
Like retroviral vectors, adenoviral vectors are constructed by
replacing host genes important for viral replication with the gene
of therapeutic interest. Generation of recombinant adenovirus
through homologous recombination at the El or E3 regions,
followed by passage through a packaging cell line that provides the
requisite El gene product in trans leads to a replication-defective
virus. In contrast to retroviral vectors, recombinant adenoviruses
can be produced at high titers. An additional advantage of these
recombinant viruses is their high level of transduction efficiency,
which results in excellent gene expression in a wide range of host
cells.
Naturally, the adenovirus system is not without disadvantages.
A humoral immune response to viral proteins, including the E2a
gene product, makes repeated administration of recombinant virus
potentially less effective. Strategies to overcome this problem have
been developed, including temperature-sensitive E 2 a mutations
and other viral gene deletions. Cytokines and immunosuppressant
medications have also been used to decrease the humoral as well
as the cell-mediated immune response to viral proteins.
The cellular toxicity of other viral proteins that may be
expressed in host cells can lead to cell death, which can make long-
term expression difficult to achieve. Long-term expression is also
inhibited by the lack of integration of adenoviral sequences into
the host genome. There is also a limitation on the length of DNA
that adenoviruses can accept. As with retroviral systems, issues of
specific delivery of adenovirus to the target cells of interest still
must be resolved.
Biological Therapy in Cancer of the Head and Neck 139

Efforts to increase the specificity and efficiency of adenovirus-


mediated gene transfer include genetically engineering specific li-
gand domains onto viral capsid proteins to enhance viral binding
18
to cognate receptors.
Other Viral Methods of Gene Delivery
Another promising candidate vector for clinical gene therapy ap-
plications is the adeno-associated virus (AAV), a nonpathogenic
linear, single-stranded DNA virus that can integrate at a specific
1 9
locus on chromosome 1 9 . The AAV can infect a wide range of
targets, including replicating as well as nonreplicating cells. In this
system, the transfected gene of interest can be integrated into the
host genome. A major limitation of the AAV has been its small ge-
nome, which necessitates the use of a helper virus, such as adeno-
virus, which can contaminate viral preparations. In addition, inef-
ficient viral packaging has led to low viral titers that have thus far
limited the use of this system in treating human diseases.
Another viral system of interest to those pursuing human gene
20
therapy is the herpesviruses. Herpes simplex virus (HSV) is a
large double-stranded DNA virus that infects nonreplicating cells
and has thus been touted as a useful vector for neural gene deliv-
ery. The pathogenicity and large genome of HSV have limited the
clinical utility of this vector system in the treatment of head and
neck neoplasms.
Several other viral systems, including poxviruses, vaccinia vi-
rus, and the insect baculovirus, are being evaluated for use as gene
15
therapy v e c t o r s . Elegant genetic engineering of the aforemen-
tioned viral systems is likely to advance these methodologies to
the point where their use in clinical medicine will be widespread.
Physical Methods of Gene Delivery
In addition to the various virally mediated gene delivery methods,
there are several physical methods for transferring genes of inter-
est into cells.
NAKED D N A . — U s i n g mechanical methods, a DNA sequence of par-
ticular interest can be directly administered to cells or tissues with-
out this "naked DNA" using viral vectors. Direct injection of DNA
into muscle has been shown to direct in vivo gene expression; how-
ever, like other methods, it is limited by a lack of control of deliv-
21
ery. This method is being evaluated clinically in several cancer
vaccination trials.
Another physical method, known as the "gene gun," uses gold
beads coated with a solution containing DNA for the gene of inter-
22
est to bombard the target t i s s u e . This method has been shown to
140 J.N. Myers

yield expression of the desired genes but is also hampered by a


lack of specificity and efficiency in delivery.
LIPOSOMES.—Cationic liposomes represent an alternative method for
gene delivery that takes advantage of the negatively charged back-
2
bone of all DNA s e q u e n c e s . ' The positively charged liposomes
coat the DNA through charge interactions, thereby protecting the
nucleic acid sequences from degradation and chaperoning them
through the negatively charged cell membrane. This leads to rela-
tively efficient though nonspecific transfection of the target cells.
Cationic liposomes are advantageous when transient rather
than long-term gene expression is needed, and their lack of immu-
nogenicity makes them ideally suited for repeated injection. Pre-
clinical studies and clinical trials have examined the efficiency and
efficacy of cationic liposome-mediated gene transfer by direct in-
tratumoral injection, aerosolized administration to diseased air-
23
ways, and systemic intravenous delivery.
Promising results have been obtained using liposome-mediated
gene delivery, and efforts are underway to improve the specificity
and efficiency of this method using antibody or ligand DNA com-
plexes. Viral components that prolong transgene expression or pro-
mote gene integration into the host genome are being genetically
engineered into the DNA-liposome in an attempt to improve the
longevity of specific gene expression.
ANTIBODY/LIGAND COUPLING.—Nonviral vector systems have also been
developed using DNA-protein complexes that deliver DNA to re-
cipient cells without using viral constructs. When DNA is com-
plexed with proteins that bind to cell surface receptors, cell speci-
ficity can be enhanced. For example, DNA complexed with the epi-
dermal growth factor (EGF) can be specifically taken up by cancer
24
cells that overexpress the EGF receptor ( E G F - R ) . Similarly, DNA
complexed with the vitamin folate can be taken up by ovarian can-
25
cer cells that overexpress the folate receptor. A major drawback
of this approach when compared with virally mediated gene de-
livery is the receptor-mediated targeting of the DNA to lysosomes,
which leads to degradation of the DNA after cell uptake.

GENE THERAPY STRATEGIES


Just as there are several methods available for the delivery of spe-
cific DNA sequences to cancer cells, there is also a variety of strat-
egies for using gene therapy to treat cancer. Some of the more com-
monly used strategies in preclinical studies and clinical trials will
be discussed, with a specific focus on the treatment of squamous
13 26 27
cell cancers of head and neck ( S C C H N J . - '
Biological Therapy in Cancer of the Head and Neck 141

Tumor Suppressor Gene Replacement


One of the most widely used strategies for cancer gene therapy is
the replacement of altered tumor suppressor genes with a normal
copy of the gene. Tumor suppresser genes encode products that are
28 30
capable of inhibiting unchecked neoplastic cell proliferation. "
However, qualitative structural alterations or a quantitative de-
crease in suppresser gene expression prevents these proteins from
carrying out their vital function in certain types of cancers. Conse-
quently, it has been thought that replacement of the underex-
pressed or mutated gene products with the wild-type tumor-
suppressor gene product at higher levels of expression could re-
13 15
verse the malignant p h e n o t y p e . '
In preclinical and clinical studies of SCCHN, this approach has
been used to target cancer cells that express mutant forms of the
3 1
tumor suppresser gene product, p 5 3 . This gene product has been
studied extensively and has been found to be among the most com-
monly altered growth regulatory genes in head and neck as well as
other cancers. Numerous studies have documented the overexpres-
sion and point mutations in p53 genes from SCCHN cell lines and
fresh tumors from various sites within the head and neck; the fre-
( , i 2 4 1
quency of mutations ranges from 2 0 % to 8 4 % . " ~
Using an adenoviral vector system, Ad5CMV-p53, Clayman and
colleagues at The University of Texas M.D. Anderson Cancer Cen-
ter were the first to introduce wild-type p53 to human head and
neck cancer cell lines that expressed mutant p53. Having first op-
timized viral transduction efficiency to maximize the uptake and
expression of wild-type p53 by the cancer cells, these investiga-
tors demonstrated wild-type p53 expression at the mRNA and pro-
31
tein l e v e l . Analysis of the resultant wild-type p53 transduced
cells grown in tissue culture and as tumors in nude mice showed
that the addition of wild-type p53 significantly inhibited cell
growth, compared with cells infected with adenovirus alone.
Mechanistic studies revealed that the addition of wild-type p53 to
these cells induced cell death, both in cells growing in culture and
in tumors implanted in nude mice. Furthermore, nonmalignant
cells infected with the Ad5CMV-p53 vector expressed wild-type
p53 at high levels but were not altered in terms of cell growth or
morphology.
In another series of studies, the same group of investigators
demonstrated that the adenovirally delivered wild-type p53 was ef-
fective in preventing tumor establishment in animals implanted
subcutaneously with SCCHN tumor cells, suggesting that p53 gene
therapy might be effective, not only in treating established tumors
142 J.N. Myers

but also in treating minimal residual disease, which is a frequent


42
source of recurrence in head and neck tumors. Curiously, adeno-
virally delivered p53 was effective in inhibiting tumor establish-
ment in SCCHN cell lines that expressed wild-type p53 as well as
those that expressed mutant p53.
The encouraging results of these preclinical studies served as
a basis for a phase I clinical trial at The University of Texas M.D.
Anderson Cancer Center of adenovirally delivered wild type p53
in patients with advanced, recurrent SCCHN. In this trial, doses as
1 1
high as 1 0 plaque forming units (PFU) were administered to pa-
tients without dose-limiting toxic effects being observed (G. Clay-
man, personal communication). Evidence of clinical activity was
also noted. Furthermore, the clinical courses of patients with re-
sectable disease who received preoperative, intraoperative, and
postoperative Ad5CMV-p53 suggest prolonged survival when com-
pared with the survival of historical control groups. The safety of
this agent and its promising antitumor activity has enabled the
principle investigators to design and implement a multi-
institutional phase II clinical trial to establish the efficacy of lo-
cally administered p53 gene therapy in the treatment of advanced,
recurrent SCCHN.

Drug Sensitivity Genes


Another promising approach to treating cancers with gene therapy
is the transfer of genes that intracellularly metabolize a relatively
13,15
nontoxic prodrug to a lethal m e t a b o l i t e . The herpes simplex
virus-encoded thymidine kinase (HSVtk) gene can be transferred
to a variety of cell types with different vector systems. Once ex-
pressed, the HSVtk protein can catalyze the conversion of ganci-
clovir to acyclovir, which is toxic to the host cell. This "suicide
gene" system has already been evaluated for antitumor efficacy and
safety in the preclinical treatment of SCCHN. O'Malley and
coworkers have used an adenoviral expression system to transfect
the HSVtk gene into SCCHN cell lines and have successfully dem-
onstrated significant tumor regression of established tumors in
nude mice after HSVtk gene delivery and ganciclovir administra-
43
t i o n . Similar results were obtained by Gluckman and colleagues
4 4 - 4 5
and another group at the University of I o w a .
Another interesting aspect of this method of gene therapy is a
now well-documented "bystander effect," in which cells adjacent
46
to the ganciclovir-treated, HSVtk-expressing cells are also killed.
This phenomenon was observed in Wilson, et al's study of head
44
and neck cell lines grown in m i c e . Scientific evidence supports
Biological Therapy in Cancer of the Head and Neck 143

several potential mechanisms for this bystander killing. Gap junc-


tions have been shown to transmit the therapeutically active me-
tabolites of ganciclovir to neighboring cells, and apoptotic vesicles
released by dying cells can be phagocytosed by adjacent cells,
47
thereby mediating cell death. Finally, an antitumor immune re-
sponse to the cells responding to therapy can ultimately lead to
immune-mediated killing of surrounding cells.

Immunomodulatory Gene Therapy


Some of the pioneering studies in clinical gene therapy were car-
ried out by investigators interested in using the immune system to
recognize and destroy malignant cells. The major area of interest
in the modulation of the immune system to treat cancers using gene
therapy is the expression of immunostimulatory cytokines at high
levels in immune effector cells, fibroblasts, or the tumors them-
48
s e l v e s . In the initial investigations, tumor-infiltrating lympho-
cytes (TIL) were extracted from tumors, transfected with retroviral
vectors bearing the genes encoding interleukin-2 (IL-2) or tumor ne-
crosis factor (TNF-a), and were then expanded prior to readmin-
49
stration to the patients.
More recently isolated cytokines have been evaluated in pre-
clinical and clinical studies: autologous fibroblasts or tumor cells
are transduced and the irradiated cytokine-expressing cells are ad-
50 51
ministered back to the t u m o r s . " Myers and Lotze have evalu-
ated the antitumor efficacy of retrovirally mediated IL-12 delivery
52
to a murine squamous cell cancer cell l i n e . Local expression of
this immunostimulatory cytokine after injection of irradiated tu-
mor cells carrying the genes for the two subunits of IL-12 expressed
under retroviral control led to inhibition of tumor establishment,
regression of established tumors, and induction of lasting antitu-
mor immunity. The promising results obtained in this study have
led to the inclusion of patients with SCCHN in a phase I IL-12 gene
therapy trial at the University of Pittsburgh Cancer Institute.
Exciting data showing synergism between suicide gene therapy
and immunomodulatory gene therapy in the treatment of squamous
53
cell cancer have been obtained by O'Malley and colleagues. In
their studies using syngeneic squamous cell carcinomas implanted
in the floor of the mouths of C3H mice, these investigators found
that gene therapy with adenovirus-HSVtk plus ganciclovir along
with adenovirus-IL-2 was much more effective than either of these
types of gene therapy alone in inducing the regression of estab-
lished tumors. It is possible that the suicide gene therapy leads to
increased release of antigens that enhance the immune response
to the tumor.
144 J.N. Myers

In some nonsquamous tumors, genes encoding costimulatory


molecules such as B 7 . 1 and B7.2 have been administered to en-
hance tumor immunogenicity. An alternative approach uses genes
encoding tumor-specific antigens to augment the immune response
to cells expressing these antigens. Although there have been more
than 50 clinical trials of gene therapy for enhancing antitumor im-
mune response, the role for immunomodulatory gene therapy in
the treatment of human cancers remains to be clearly defined.

Antisense Strategies
During the past decade, antisense oligonucleotides and antisense
gene therapy vectors for the treatment of cancer have been areas of
54
intensive research activity. These novel technologies provide very
specific means of decreasing the expression of gene products es-
sential for the maintenance of the cancerous state. Antisense thera-
peutics take advantage of the specific base pairing of nucleic acids:
a short oligonucleotide or an antisense RNA transcript complemen-
tary to a gene of interest can bind to the gene's sense transcript and
prevent translation of functional protein by several mechanisms.
Through steric hindrance, the oligonucleotide can inhibit ribosome
assembly, message capping, splicing, and polyadenylation. In ad-
dition, oligonucleotide DNA/RNA hybrids can serve as substrates
for cellular RNAse H, which degrades the mRNA. An additional
mechanism through which some antisense reagents can decrease
gene expression is through nucleotide-mediated catalytic cleavage.
If designed properly, antisense therapeutics not only can recognize
a target gene of interest, it can also acquire a tertiary structure that
enables them to cleave the target message. These oligonucleotides
are known as hammerhead ribozymes, and their potential therapeu-
tic value is under investigation in preclinical studies.
Several qualities are requisite to the success of antisense nucle-
otides as therapeutic agents. A successful oligonucleotide must be
stable in serum and cells, must be readily taken up by cells, must
have only limited interactions with other cellular components, and
must have very specific base pair binding to cellular nucleic acid
54
targets. Because the normal phosphodiester backbone of nucleic
acid is readily degraded by a variety of serum and cellular nucle-
ases, chemically modified oligonucleotides have been designed to
resist nuclease destruction. However, certain chemically altered
oligonucleotides have nonspecific cellular toxicity. To enhance the
uptake of oligonucleotides by cells, oligonucleotides may be com-
plexed with cationic liposomes, polylysine, or other cationic com-
pounds.
Biological Therapy in Cancer of the Head and Neck 145

There have been encouraging preclinical studies with antisense


therapeutics, and some clinical data suggest that these may be
safely administered. However, to date there have been no reported
clinical trials of antisense treatment of head and neck cancer.
Antibody-Mediated Therapies
The search for tumor-specific antigens that can be targeted for di-
agnostic and therapeutic purposes is an active area of investiga-
tion in the field of head and neck oncology. Monoclonal antibody
technology and the search for autologous antibodies have been
fruitful methods for identifying SCCHN antigens. Several years ago,
Vlock and Carey and their colleagues tested the sera of patients
with SCCHN against a panel of SCCHN cell lines and other cell
types and found that 23 of 41 patients studied had autologous an-
tibody reactivity to SCCHN that could be augmented by acidifica-
5 5 , 56
tion and ultrafiltration of the s e r a . Western blot analysis with
these sera revealed a 60-kD SCCHN-associated glycoprotein that
r 7
had been purified by column chromatography. ' However, further
structural and functional analysis of this antigen will be required
to determine its utility as a target for biological therapies.
Several groups of investigators have attempted to identify SC-
CHN antigens by preparing monoclonal antibodies. A general strat-
egy for developing such antibodies is the immunization of mice
with human SCCHN cells and fusion of spleens from the immu-
5 8 - 6 0
nized mice with mouse myeloma c e l l s . After limiting dilution,
resulting hybridoma clones are selected for specific binding to SC-
CHN cells relative to normal squamous mucosa and other cell
types, and positive clones are expanded for further analysis. Using
this approach, van Waes and Carey identified an SCCHN antigen,
A 9 , that was found to be expressed by squamous cell carcinomas,
adenocarcinomas, and transitional cell carcinomas but only at the
61
basal surface of normal keratinocytes. Further characterization re-
vealed that this antigen was identical to the extracellular matrix
binding protein a6b4 integrin and that this receptor mediated cell
62
attachment to l a m i n i n . Additional studies have shown that pat-
terns of A9 staining on frozen tumor sections correlate with clini-
cal outcome and that patients with more intense, nonpolarized A9
61
staining have a higher rate of early relapse. These findings and
the results of studies using SCCHN tumor xenografts in mice indi-
cate that antibodies to A9 may also have a role in immunolocaliz-
ing tumors in patients using radiolabeled antibody conjugates and
63
nuclear medicine s c a n s . The therapeutic potential of these anti-
bodies has yet to be realized, but studies along these lines have
been quite promising.
146 J.N. Myers

Using a similar approach to identify SCCHN antigens, a group


led by Snow and van Dongen has developed several monoclonal
antibodies that appear to have tremendous potential in the staging
64
and treatment of head and neck c a n c e r . The E48 and U36 mono-
clonal antibodies have been coupled to radiolabels, Iodine-131,
rhenium-186, and technetium-99, and have been shown to bind
normal squamous and transitional epithelia, as well as a number of
65 66
SCCHN cell lines and tumors in s i t u . ' Radioimmunoscintigra-
phy with technetium-99-labeled monoclonal antibody E48 IgG or
Fab portion of the antibody effectively localized cervical lymph
86
node metastases in patients with SCCHN in a recent clinical trial.
131
Studies with I - l a b e l e d monoclonal antibody U36 indicate that
this antibody may be even more effective for tumor localization
67 186
studies. Studies of R e - l a b e l e d monoclonal antibody E48 to
treat human SCCHN xenografts in nude mice have shown dose-
dependent regression of tumor, suggesting that radioimmuno-
186
therapy of SCCHN with R e - l a b e l e d monoclonal antibody E48
68
may be a useful approach for the treatment of this d i s e a s e .
More recently, a chimeric form of the E48 antibody has been
developed that incorporates human antibody domains. This new
antibody design should increase immunologically mediated killing
of tumor cell targets and decrease the immunogenicity of the agent
69
itself.
Another promising area of investigation is the use of the E48
and U36 antibodies to induce antibody-dependent cellular cytox-
icity. In vitro assays performed with SCCHN cell lines and mouse/
human chimeric antibodies derived by the van Dongen group have
shown that arming of human peripheral blood mononuclear or hu-
man purified IL-2 activated natural killer (NK) cells with anti-
SCCHN monoclonal antibodies leads to effective tumor cell kill-
70
i n g . Further studies are in progress to determine if these antibod-
ies will effectively mediate the killing of SCCHN tumor cells in
vivo in immunosuppressed nude mice. The therapeutic potential
of arming IL-2-activated effector cells with chimeric anti-SCCHN
monoclonal antibodies for more effective delivery of these cells to
the tumor is being evaluated.
C225 is another promising, potentially therapeutic antibody
currently being evaluated for its safety and antitumor efficacy in
71
patients with advanced SCCHN. C225 is a humanized murine
72
monoclonal antibody that binds to E G F - R . This drug may be par-
ticularly useful for treatment of SCCHN, because there are abun-
dant data to suggest that aberrant expression of EGF-R may play a
73
role in the pathogenesis of S C C H N .
Biological Therapy in Cancer of the Head and Neck 147

Most studies of EGF and EGF-R in SCCHN have involved the


evaluation of the amount of growth factor or receptor expression at
the DNA, RNA, or protein level in cell lines or fresh tissues and the
3 5 7 4 - 8 2
correlation of these findings to clinical p a r a m e t e r s . ' Al-
though conflicting data have been obtained, some general trends
have been noted. In an immunohistochemical analysis of 18 fresh
specimens of SCCHN of the tongue base, EGF-R and transforming
growth factor alpha (TGF-a) were routinely seen in normal squa-
mous mucosa adjacent to the tumors. Overexpression of the EGF-R
35
and TGF-a was seen in 6 0 % and 3 5 % of tumors, respectively.
However, overexpression appeared to have no impact on survival.
Similar results were seen in an analysis of tumors of the nasal cav-
79
ity and paranasal s i n u s e s . In a study of 103 laryngeal tumors,
EGF-R expression was elevated in tumors, particularly those that
81
were poorly differentiated, when compared with normal m u c o s a .
In addition, the 2-year survival of patients with EGF-R-positive tu-
mors was 5 8 % , compared with 8 2 % for patients with EGF-R-
negative lesions.
To investigate further the role that expression of TGF-a and
EGF-R may be playing in the pathogenesis of SCCHN, Grandis and
Tweardy systematically evaluated the level of mRNA encoding
these two proteins in tumors and normal mucosa from patients
with tumors, as well as in normal mucosa from patients without a
82
history of tobacco or alcohol u s e . In their analysis, 9 5 % of histo-
logically normal samples in patients with SCCHN and 8 7 . 5 % of
tumors had fivefold higher TGF-a mRNA levels compared with lev-
els in normal mucosa. Levels of mRNA for the EGF-R were elevated
by 29-fold in 9 1 % of histologically normal tissue from tumor-
bearing patients, and 69-fold in 9 2 % of tumors compared with lev-
els in normal mucosa. The high levels of both the ligand and re-
ceptor in tumors and normal mucosa from patients with head and
neck cancer suggest that environmental influences, such as tobacco
and alcohol use, lead to upregulation of growth factor production
and receptor expression that may play a role in tumor develop-
ment, possibly through autocrine stimulation of cell proliferation
through normal cellular growth pathways.
Some functional data to support this hypothesis come from a
study of two SCCHN cell lines that were examined for levels of
EGF-R expression by immunoprecipitation of metabolically labeled
83
cells with specific anti-EGF-R antibodies. In this study, the cell
line that grew more efficiently in plating assays was found to have
fivefold higher levels of EGF-R. The immunoprecipitated receptors
were also analyzed for intrinsic tyrosine kinase activity, which is
148 J.N. Myers

indispensable for EGF-R signal transduction, using an in vitro ki-


nase assay with radiolabeled adenosine triphosphate. The more
rapidly proliferating cell line was found to possess greater kinase
activity. Furthermore, kinase activity was increased in immunopre-
cipitates from both cell lines by the addition of exogenous EGF.
The identification of the overexpression of EGF-R and its ligand
T G F - a in a large number of SCCHN makes this receptor system a
potential target for various biological therapies. In exploring this
target, Sturgis and colleagues evaluated the effects of a murine
monoclonal antibody, Mab 5 2 8 , specific for the extracellular do-
main of EGF-R on the proliferation and differentiation of three head
84
and neck cell lines grown as monolayers and as tumor spheroids.
These three tumor lines were found to express high levels of EGF-R
and were inhibited in their proliferation by antibody treatment.
Two of the cell lines were also induced to differentiate by this anti-
body, as evaluated by the expression of involucrin as well as corni-
fied envelope production.
The Mab 528 and C225, a humanized chimeric form of a mu-
rine monoclonal antibody, were developed and characterized in Dr.
72
John Mendelsohn's laboratory. The C225 antibody binds to EGF-R
and inhibits specific ligand binding and, therefore, the ligand-
induced receptor autophosphorylation and downstream stimula-
tory effects on cell proliferation. As mentioned previously, these
antibodies can inhibit the growth of human cancer cells in vitro
and the growth of tumor cells implanted subcutaneously in nude
72
m i c e . In addition, C225 has been shown to act synergistically
with cisplatin to inhibit tumor growth and cure nude mice with
established tumor xenografts.
Several clinical trials of the anti-EGF-R antibody C225 in dif-
ferent types of human cancers, including SCCHN, have shown this
85
to be a safe agent. A phase I trial evaluating the toxicity and tu-
mor saturation by the C225 antibody administered in combination
with cisplatin is currently underway at the University of Texas
M.D. Anderson Cancer Center.

IMMUNOTHERAPY FOR CANCER OF THE HEAD AND NECK


The theory of immunosurveillance, which is based on the work of
Paul Ehrlich and other investigators dating back to the early 1900s,
holds that specific effector molecules and cells of the immune sys-
tem recognize and eradicate neoplastic cells, thereby preventing tu-
86 87
mor f o r m a t i o n . ' By extension, the theory predicts that immu-
nomodulation can be an effective means of anticancer therapy. This
Biological Therapy in Cancer of the Head and Neck 149

section will briefly review the evidence in support of the theory of


immunosurveillance and discuss some of the immunomodulatory
agents studied to date and their applicability to cancer of the head
and neck.

EVIDENCE FOR THE THEORY OF IMMUNOSURVEILLANCE


Evidence in support of control of tumor growth through immuno-
surveillance includes the spontaneous regression of tumors in in-
dividuals with very advanced or widely metastatic disease; the in-
creased frequency of malignancies in patients who are immuno-
suppressed by a genetic defect, systemic disease, or iatrogenic
means; the augmented antitumor response of patients treated with
immunostimulatory agents; and the presence of activated immune
88,89
effector cells in tumor i n f i l t r a t e s .
There have been a number of reports in the literature of pa-
tients with a variety of tumor types whose tumors regressed spon-
taneously with no or minimal therapeutic intervention. With re-
gard to head and neck cancer, Levine and colleagues reported a lack
of detectable tumor at autopsy in the case of a patient who had an
incompletely resected laryngeal squamous cell carcinoma and died
90
of other causes 12 years later.
Further support for the validity of the theory of immunosur-
veillance comes from patients with primary immunodeficiencies,
who have been found to have up to a 100-fold increased risk of
9 1 , 9 2
developing c a n c e r . The most common types of cancer seen
in patients with immunodeficiency diseases such as Wiskott-
Aldrich syndrome, ataxia-telangiectasia, common variable im-
mune deficiency, or severe combined immunodeficiency include
non-Hodgkin's lymphoma, leukemia, gastric carcinoma, and
93, 94
Hodgkin's d i s e a s e . Patients infected with the human immu-
nodeficiency virus have been noted to have an increased inci-
dence of Kaposi's sarcoma and non-Hodgkin's lymphoma. In
addition, squamous cell carcinoma of the oral cavity and larynx
9 5 9 7
has been reported in patients with A I D S . Patients immuno-
suppressed with cyclosporin A, tacrolimus, prednisone, azathio-
prine, or other means to prevent rejection of allogeneic organs or
tissues have also been reported to have an increased incidence
of several tumor types including Kaposi's sarcoma, non-Hodgkin's
91
lymphoma, and various c a r c i n o m a s . Bradford and colleagues
reported on three renal transplant recipients without tradition-
al risk factors for developing SCCHN who subsequently devel-
oped this type of tumor receiving systemic immunosuppressant
98
therapy.
150 J.N. Myers

CELLULAR CANCER IMMUNOTHERAPY


The identification of immune effector cells capable of destroying
human cancer cells has propelled the development of the field of
cancer cellular immunotherapy. Studies by Gross and then Prehn
and Main dating back to the 1940s demonstrated that inbred mice
could be immunized to tumors that had arisen in mice of the same
19,100
strain.' The Hellstroms and colleagues identified lymphocytes
from cancer patients that inhibited the growth of cancer cells in
101
vitro. Further work along these lines demonstrated that periph-
eral blood cells, later termed natural killer or NK cells, are capable
of killing a variety of types of human cancer cells in culture in a non-
102
major histocompatibility complex (MHC)-restricted m a n n e r .
These cells were also shown to be able to eliminate tumor cells in
the circulation of experimental animals.

IMMUNOTHERAPY WITH IL-2


Several significant advances in the field of cellular cancer immu-
notherapy have resulted from the discovery of IL-2, which facili-
1 0 5 1 0 4
tates the in vitro expansion and cloning of T c e l l s . ' Rosen-
berg and colleagues at the Surgery Branch of the National Cancer
Institute have used IL-2 to expand peripheral blood mononuclear
cells in culture and have shown that the resulting lymphokine ac-
tivated killer (LAK) cells have activity against tumor cells in vitro
and in vivo in animal models, as well as against disseminated mela-
noma and renal cell carcinoma in patients treated in clinical tri-
1 0 5
a l s . The evidence that LAK activity is composed of NK activity
as well as cytotoxic T cell responses has led to the search for spe-
cific epitopes on tumor cells recognized by T cells and to the in
vitro expansion and therapeutic administration of IL-2-activated
106
TIL to cancer patients by Rosenberg's g r o u p . The premise upon
which these studies were based and which still persists today is
that lymphocytes isolated from tumors are more likely to be reac-
tive to specific tumor antigens than are cells isolated from the pe-
ripheral blood or spleen.
Treatment of cyclophosphamide-treated nude mice bearing
human SCCHN xenografts with human LAK cells and IL-2 com-
pletely inhibited the growth of implanted tumors, suggesting that
this type of treatment may be effective for treating patients with
1 0 7 1 0 8
SCCHN. ' A clinical phase I trial of IL-2/LAK therapy in pa-
tients with SCCHN by Squadrelli-Saraceno and colleagues demon-
strated six partial or minimal responses in 14 patients with tumors
larger than 20 cm in diameter. Patients in this trial received 10 lo-
6
cal injections of recombinant IL-2 from 2 4 , 0 0 0 U/day to 1.8 X 10
109
U / d a y . Iwaka and colleagues administered autologous LAK to
Biological Therapy in Cancer of the Head and Neck 151

four patients with carcinoma of the maxillary sinus by direct arte-


rial infusion and documented a decrease in tumor volume as well
110
as an increase in lymphocytic infiltration of the t u m o r .
The anticancer efficacy of adoptive transfer of IL-2-activated
NK cells (A-NK) has been evaluated by adding A-NK cells to SC-
CHN tumor spheroids in vitro and to immunosuppressed nude
mice bearing established 7-day SCCHN xenografts in vivo. Treat-
ment with these cells induced complete tumor regression, as did
the treatment of SCCHN xenograft-bearing mice with A-NK culture
supernatants, which have been shown to contain a mixture of cy-
1 1 1 1 1 2
tokines. ' These encouraging results indicate that clinical tri-
als of adoptive immunotherapy with A-NK cells are warranted.
Squamous cell cancer of the head and neck lends itself to locore-
gional treatment with biological agents, because it tends to grow
and recur locally, is readily accessible, and is well infiltrated with
lymphocytes.
Preclinical and clinical evaluations of adoptive therapy with
TIL have not been extensively carried out in SCCHN because TIL
isolated from SCCHN have had impaired proliferative responses to
a variety of mitogens and depressed cytotoxicity against different
target cells when compared with peripheral blood lymphocytes.
Furthermore, multiple attempts at sensitization of TIL with autolo-
gous tumor cells in an effort to generate SCCHN-specific cytotoxic
113
T lymphocytes have been u n s u c c e s s f u l . However, Dr. Theresa
Whiteside's group has recently established human cytotoxic T cell
lines specific for autologous SCCHN from the peripheral blood of
113
a patient with a primary lesion of the oral t o n g u e . These cells
are CD3 + C D 8 + C D l l b - H L A - D R + T C R a / 0 + and were found to lyse
labeled autologous and three allogeneic SCCHN tumor lines but not
normal keratinocytes or a variety of other tumor cell targets in stan-
dard cytotoxicity assays. This lysis was inhibited by antibodies to
TCR, CD3, and MHC class I antigens, indicating that the cytolytic
T cells recognize a shared antigen expressed on SCCHN and that
the recognition is MHC class I restricted. Studies are underway to
identify the SCCHN-specific antigen recognized by these cytotoxic
T lymphocytes (T. L. Whiteside and S. Yasumura, unpublished ob-
servations).

IL-2 IMMUNOTHERAPY FOR CANCER OF THE HEAD AND NECK


Interleukin-2 is the biological agent that has been most thoroughly
evaluated for the treatment of head and neck cancer. Preclinical
modeling of the potential of this agent for treating SCCHN in mu-
rine xenograft models has been performed by several groups and
has indicated the potential utility of treating patients with SCCHN.
152 J.N. Myers

Forni and colleagues treated patients with recurrent SCCHN


6
with daily regional injections of 200 to 5 X 1 0 U/day of natural IL-2
for 10 days and achieved three complete responses, three partial re-
114
sponses and seven minimal responses in 20 patients t r e a t e d . All
patients eventually had recurrence of their disease, and no effects
on NK or LAK activity were noted.
In a phase II trial performed by the same group, IL-2 was given
preoperatively by daily injections of 100 U intratumorally, and 100
U into level II of the neck for 10 days. Although the tumors and
regional lymph nodes excised at the time of surgery had increased
lymphocytic and eosinophilic infiltration on histologic analysis
when compared with non-IL-2 treated patients, the clinical benefit
115
of this treatment was l i m i t e d .
In a phase lb study performed at the University of Pittsburgh
Medical Center, 36 patients with unresectable SCCHN were treated
with peritumoral injections of recombinant IL-2 ranging from 200
6
to 4 x 1 0 U/day for 5 of 7 days for a 2-week period, and toxic ef-
116
fects and immunologic parameters were m o n i t o r e d . Analysis of
paired pretherapy and posttherapy biopsy specimens demonstrated
an increase in the number of T cells and NK cells infiltrating the
tumor stroma and parenchyma after IL-2 treatment, with a much
larger increase in the number of NK cells. Functional analyses in-
dicated increases in LAK, NK, and autologous tumor cytolytic ac-
tivity as determined by chromium-51 release assays with labeled
Daudi cells, K 5 6 2 , and in some cases, autologous tumor targets.
Analysis of peripheral blood lymphocytes as well as fresh TIL in-
dicated systemic immune activation by local IL-2 administration.
Several groups have attempted to treat patients with SCCHN
with combination therapy including systemically administered re-
combinant IL-2. In a trial of IL-2, cisplatin, and 5-fluorouracil, two
of 11 patients had complete responses and four had partial re-
117
s p o n s e s . When this same regimen was used to treat 25 patients,
one complete response and six partial responses were seen. These
results, however, were not significantly better than those seen with
118
chemotherapy a l o n e . A trial of systemic recombinant IL-2 (3 X
8 2 6 2
1 0 U/m /day) and interferon-a (5 X 1 0 U/m /day) was discontin-
ued despite partial responses in two of 11 patients because of toxic
119
effects.

OTHER CYTOKINES USED IN IMMUNOTHERAPY FOR CANCER


OF THE HEAD AND NECK
The use of IFN to treat SCCHN has been evaluated by several
groups. In a study at the University of Pittsburgh Medical Center,
Biological Therapy in Cancer of the Head and Neck 153

the relative efficacies of high-dose and low-dose systemic recombi-


6
nant IFN-a were studied. One of 28 patients treated with 6 X 1 0
U/day of IFN-7 for 3 days had a complete response and one of 31
7
patients treated with 12 X 1 0 U/day had a complete response;
whereas nine other patients treated with this regimen had stable
120
d i s e a s e . One of fourteen patients treated with systemic recombi-
7
nant IFN-a at 1 x 1 0 U/day for 3 days every 28 days for a minimum
of 3 months had a complete response, and another two had stable
121
d i s e a s e . Comparable response rates were seen earlier in several
122
other trials of IFN-a in head and neck c a n c e r .
In a trial of intravenously administered IFN-7, Richtsmeier and
2
colleagues treated eight patients with SCCHN with 50 u.g/m IFN-7
over 24 hours once a week for 4 weeks. One patient had a com-
plete response as well as histologic evidence of tumor differentia-
123
tion and n e c r o s i s . Whereas preclinical models support the anti-
tumor effects of IFN-7 on SCCHN in cell culture and in murine xe-
nografts, further clinical evaluation of this cytokine is needed to
111
determine its therapeutic potential for patients with S C C H N .
Another cytokine that appears to be a promising agent for the
treatment of human tumors is I L - 1 2 . This heterodimeric cytokine
is produced by antigen-presenting cells (APCs), and it stimulates
the generation of a T cellular immune response. Preclinical stud-
H 1

ies with this cytokine have shown it to have potent antitumor ef-
124
fects when administered either locally or s y s t e m i c a l l y . In addi-
tion, transduction of syngeneic fibroblasts with the IL-12 gene pro-
vides a cellular vehicle for IL-12 gene therapy that has also been
effective in preventing tumor establishment and inducing the re-
50
gression of established tumors in tumor m o d e l s . Initial studies
of systemic recombinant IL-12 in the treatment of immunocompe-
tent mice implanted with SCCVII squamous cell carcinoma cells
using systemic recombinant IL-12 and IL-12 gene therapy indicate
52
that this might be a useful agent in the treatment of SCCHN. Cur-
rently, phase I and II trials of recombinant IL-12 and IL-12 gene
therapy are underway.

ANTIGEN PRESENTING CELLS IN IMMUNOTHERAPY


Whereas studies of immunotherapy using cytokines or cytokine
gene therapy for the treatment of cancer have been promising, some
recent studies indicate that the antitumor immune response can be
improved upon by optimizing the "presentation" of tumor antigens
1 2 5 1 2 0
to the immune s y s t e m . ' It has been understood for some time
that the cellular immune system recognizes tumor-specific pep-
tides complex with MHC proteins on the surface of APCs. In addi-
154 f.N. Myers

tion, data accumulated during the past several years indicate that
the presence of a sufficient number of costimulatory molecules ex-
pressed on the surface of the APCs can enhance the immune re-
sponse to the tumor. The cell-surface proteins CD40, B 7 - 1 , and B7-2
in particular have been shown to be important for costimulating
1 2 6 1 2 7
the activation of antigen-specific T c e l l s . '
Dendritic cells are bone marrow-derived cells that express
CD40, B 7 - 1 , and B7-2 abundantly. They also express MHC antigens
and DEC-205, another antigen-presenting molecule and are be-
1 2 5 1 2 6
lieved to be the most potent APCs characterized to d a t e .
Studies have shown a more favorable prognosis in patients with
SCCHN whose tumors had more infiltration with dendritic cells on
1 2 8 , 1 2 9
immunohistochemical e v a l u a t i o n . This observation suggests
that the presence of dendritic cells in head and neck tumors may
more effectively stimulate the immunosurveillance and therefore
improve the patient's prognosis. Cancer immunobiologists are cur-
rently trying to exploit the potent APC activity of dendritic cells
to therapeutic benefit. Preclinical data using murine dendritic cells
pulsed in vitro with known tumor-specific peptides have been
shown to be an effective antitumor agent when the antigen-pulsed
1 1 3 1
cells are administered to tumor-bearing syngeneic m i c e . ' " ' ' Ad-
ditional work has shown that human dendritic cells pulsed with
specific tumor antigens are capable of inducing tumor specific
T-cells in tissue culture. The goal of current clinical investigations
at the University of Pittsburgh Cancer Center under the direction
of Dr. Michael Lotze and Dr. Walter Storkus is to generate tumor
reactive T cells in vivo by administering autologous dendritic cells
pulsed with tumor-derived peptides to enhance the antitumor im-
mune response.

SUMMARY
Exciting progress in the molecular and cell biology of head and
neck cancer has provided us with new ways to target cancer cells
more specifically. The possibility now exists with gene therapy of
targeting specific genetic defects found in certain tumor types us-
ing any one of a number of possible gene delivery systems.
Although specific problems with currently existing gene therapy
strategies remain to be addressed, encouraging preclinical and
clinical data indicate that this is a very promising area. In addi-
tion, the exquisite sensitivity of antibodies directed at tumor-
specific targets should make antibody-conjugated toxins, radioim-
munoconjugates, and antibodies alone viable therapeutic options.
Biological Therapy in Cancer of the Head and Neck 155

Finally, increased understanding of the antitumor immune re-


sponse has yielded more rationally designed cytokine as well as
cellular-based immunologic treatments for cancer.
During the next several years, physicians and scientists alike
will need to critically appraise the results of clinical trials of some
of these novel treatment approaches and determine how they will
fit in with the existing options for the treatment of patients with
head and neck cancer. Given that these tumors arise from a num-
ber of molecular aberrations that occur during the immune
response, it is likely that biological therapies will be used in com-
bination with other biological approaches or more conventional
treatment modalities.

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head and neck squamous carcinoma. Cancer 71:2326-2331, 1993.
120. Agarwala S, Vlock D, Johnson JT, et al: Phase II trial of interferon-alpha
in locally recurrent or metastatic head and neck cancer: Results of
ECOG trial P-Z386. Proceedings of the American Society of Clinical
Oncology :684, 1991.
121. Vlock D, Johnson JT, Myers E, et al: Preliminary trial of non-
recombinant interferon-alpha in recurrent squamous cell carcinoma
of the head and neck. Head Neck 13:15-21, 1991.
122. Medenica R: Cyclic therapy schedule of human leukocyte interferon
in advanced head and neck squamous cell carcinoma. Proceedings of
the International Conference on Head and Neck Cancer :77, 1984.
123. Richtsmeier WJ, Koch WM, McGuire WP, et al: Phase I-II study of ad-
vanced head and neck squamous cell carcinoma patients treated with
recombinant human interferon gamma. Arch Otolaryngol Head Neck
Surg 116:1271-1277, 1990.
124. Nastala CL, Edington H, Storkus WJ, et al: Recombinant interleukin-12
administration induces tumor regression and high levels of interferon-
gamma. / Immunol 153:1697-1706, 1994.
125. Austyn J: The dendritic cells system and anti-tumor immunity. In vivo
7:271-296, 1993.
126. Steinman R: Dendritic cells and immune-based therapies. Exp Hema-
tol 24:859-862, 1996.
127. Zitvogel L, Robbins PD, Storkus WJ, et al: Interleukin-12 and B7.1 co-
stimulation cooperate in the induction of effective antitumor immu-
nity and therapy of established tumors. Eur ] Immunol 26:1335-1341,
1996.
128. Gallo O, Libonati GA, Gallina E, et al: Langerhans cells related to prog-
nosis in patients with laryngeal carcinoma. Arch Otolaryngol Head
Neck Surg 117:1007-1010, 1991.
129. Kerrebijn JD, Balm AJ, Knegt PP, et al: Macrophage and dendritic cell
infiltration in head and neck squamous-cell carcinoma: An immuno-
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dritic cells induce antigen-specific CTL-mediated protective tumor
immunity. / Exp Med 183:283-287, 1996.
CHAPTER 9
Septoplasty and
Rhinoplasty in the
Pediatric Age Group
Stephen S. Park, M.D.
Assistant Professor, Department of Otolaryngology-Head and Neck
Surgery; Director, Division of Facial Plastic and Reconstructive Surgery,
University of Virginia Medical Center, Charlottesville, Virginia

Charles W. Gross, M.D.


Professor, Department of Otolaryngology-Head and Neck Surgery and
Pediatrics; Director, Division of Pediatric/Otolaryngology, University of
Virginia Medical Center, Charlottesville, Virginia

S eptoplasty and rhinoplasty remain some of the most common


procedures performed by the otolaryngologist - head and neck
surgeon, and yet there remains active discussion on the ideal tech-
niques, particularly as they pertain to the pediatric age group. Sep-
tal surgery has a long history in the field of otolaryngology, dating
back to 1875 when Adams reported the repair of the traumatized
1
nose through fracturing and splinting the nasal septum. The year
1899 marked the beginning of a formal septoplasty, with Asch de-
scribing techniques for altering the spring of the deflected cartilage
2
through full-thickness cruciate incisions. At the turn of the cen-
tury, Freer and Killian described the methods of a submucous re-
section for surgical repair of the deviated septum, and their gen-
3
eral methods remain in use by some otolaryngologists today. Cottle
first introduced the concept of a conservative septoplasty in 1947,
and he elaborated on the disadvantages associated with the tradi-
tional submucous resection. Although Cottle's techniques remain
the standard for contemporary septoplasty, newer modifications
4 5
and innovations continue to surface. '

EMBRYOLOGY AND ANATOMY


Understanding the embryologic development of the nose explains
some of the anatomical distinctions between the pediatric and
Advances in Otolaryngology-Head and Neck Surgery®, vol. 12
e
1 9 9 8 , Mosby, Inc. 1°"*
166 S.S. Park and C.W. Gross

adult groups. T h e nose begins in the third week of gestation with


the development of paired olfactory p l a c o d e s . D e e p e n i n g of both
nasal pits slowly gives rise to a central frontonasal process that rep-
resents the primitive nasal septum. Septal development continues
by virtue of anterior palatal growth as well as posterior extension
through the bucconasal membrane. During this period, the fetal
septum is composed entirely of cartilage that forms via mesenchy-
mal condensation originating from the sphenoid. The perpendicu-
lar plate of the ethmoid begins ossification from the sphenoid area
and proceeds anteriorly and dorsally throughout childhood and
into adolescent life. The final anterior limit of this ossification re-
mains variable and can come to rest immediately under the nasal
spine of the frontal bone or extend to the caudal-most aspect of
the nasal bones. The vomer, on the other hand, does not undergo
direct ossification but becomes bone from the paired connective tis-
sue lamellae found on either side of the primitive cartilaginous
vomer. This cartilage progressively resorbs while the vomerine
plates fuse and grow toward the perpendicular plate superiorly and
the quadrilateral cartilaginous septum anteriorly. Similarly, the fi-
nal resting point is variable with continued development after
birth.
In children, the quadrilateral cartilaginous septum comprises
a greater proportion of septum than found in adults because the
ossification process continues beyond birth and into the early years
of life. The attachment of the cartilaginous septum to the maxil-
lary crest and vomer is primarily fibrous and more loosely fixed in
the pediatric group. This loose articulation allows for easy subluxa-
tion at the bony-cartilaginous junction, thus serving as a "shock
absorber" against blunt anterior forces. The external nasal skeleton
is also proportionally more cartilaginous than bony in the earlier
years; a child's nasal bones are relatively short as compared with
adults. Pediatric nasal bones are not fused completely in the dor-
sal midline and thus resemble the "open roof" deformity seen dur-
ing a reduction rhinoplasty. This lack of fusion allows for subtle
mobility between the bones in response to trauma but can also re-
semble a telescope-type injury to the unsuspecting physician. The
lack of nasal projection with respect to the prominent forehead is
another distinguishing feature. These developmental characteris-
tics all contribute to the paucity of nasal fractures seen in young
children.

PATHOPHYSIOLOGY
Whereas the etiology of external nasal deformities is generally self-
evident and often discussed, the pathophysiology of septal deflec-
Septoplasty and Rhinoplasty in Pediatric Group 167

tions remains poorly understood. Fractures of the septum and sub-


sequent spurs probably arise from absorbing the forces translated
from external blunt trauma. Location of the septal fracture can be
anticipated by the supporting mechanisms found around the nasal
septum. Vertical caudal fractures arise from oblique forces to the
nasal tip, where the midseptum is reinforced by its attachments to
the upper lateral cartilages. When upper lateral cartilages are par-
ticularly short, these vertical fractures may run a more oblique
course. Forces transmitted to the bony cartilaginous junction will
cause oblique fractures if the cartilage is securely seated in the pos-
terior bony septum or if a subluxation is poorly fixated. Forces
transmitted inferiorly at the maxillary crest will typically cause a
cartilaginous dislocation with the septum resting on one side of
the floor of the nose.
The general bowing or gradual deflection of the cartilaginous
septum is less clearly defined. More subtle forces to the external
nose may leave partial thickness fractures that disrupt the intrin-
sic stability of the native cartilage. Although insufficient to cause
obvious fractures or subluxations, the intrinsic forces may be al-
tered enough that septal development continues with progressive
bowing. The contribution of these intrinsic forces of cartilage is
witnessed during partial thickness incisions, where these dynam-
ics are used during septoplasty techniques.

PEDIATRIC CONSIDERATIONS
Uncorrected facial trauma in the growing child can impair growth
of the midface. Periosteal elevation of the maxilla and miniplate
fixation of craniotomies have both been shown to stunt normal
7 9
growth in the animal m o d e l . " Canady, et al used the frontonasal
suture of weanling rabbits to show a continuum of restricted
growth from the sham operation, to semirigid fixation (analogous
10
to resorbable plates), to standard rigid fixation. It is our feeling
that significant maldevelopment can occur from displaced facial
fractures that are left unrepaired. Although exposure and perios-
teal elevation may compromise bony viability and potential
growth, displaced or distracted fragments probably have a greater
impact on facial maldevelopment. Accurate closed reduction usu-
ally represents the method of choice for managing craniofacial frac-
tures in the pediatric age group.
These observations of impaired development after significant
early facial trauma have led authors to extrapolate to the care of
nasal fractures as well as elective nasal and septal surgery. Studies
have attempted to identify those areas of the nasal septum that are
168 S.S. Park and C.W. Gross

most critical in growth of the midface. Resection of specific areas


of the septum have been correlated with impeded nasal growth us-
1 1 , 1 2
ing the animal m o d e l . Other areas of the cartilaginous septum
have correlated with increased metabolic activities, suggesting a
more active role in growth function and greater need for its pres-
1,1
ervation. There are clinical reports of septoplasty performed in
children that, after sufficient follow-up, have suggested a shorten-
14
ing of the dorsal length of the n o s e .
This concern over jeopardizing potential growth of the nose has
led surgeons to more conservative approaches with nasal and sep-
tal pathology, including watchful waiting in anticipation of spon-
taneous correction. Gray has shown, however, that a deviated sep-
tum in young children will not spontaneously improve with nor-
15
mal growth and development. Furthermore, it has been suggested
that chronic mouth breathing from nasal obstruction can cause cra-
16
niofacial dysmorphology in young c h i l d r e n . Otolaryngologists
are familiar with the characteristic "adenoid facies" seen in chil-
dren with adenoid hypertrophy and chronic nasal obstruction. And
finally, nasal deformity left untreated can also bring about a sig-
nificant psychosocial impact; in some circumstances, the nasal dys-
morphology can have a lasting effect on general self-esteem and
self-image. Collectively, these factors have led people to revisit the
dogma that nasal surgery in the pediatric age group should be taboo.
Aggressive resection of the entire nasal septum clearly impacts
normal nasal development, but certain areas of the nasal septum ap-
pear more vulnerable than others. "Growth centers" are located
along the posterior dorsal septum, around the bony cartilaginous
1 7
junction, and along the anterior caudal septum (Fig l ) . More re-
cent studies have attempted to determine how aggressive one can be
with septal surgery while ensuring normal facial development. Uni-
lateral or bilateral elevation of the mucoperichondrium alone has
11
permitted normal facial growth. Resection of the posterior carti-
laginous septum with an intact perichondrium (submucous resec-
18-20
tion) also has been well t o l e r a t e d . Even aggressive approaches
to the nasal skeleton, including the sublabial and open, degloving
approaches with resection and replacement of the cartilaginous
2 1 - 2 3
septum have been reported without long-term s e q u e l a e .
Our opinion on septoplasty in the pediatric age group is that
the modern techniques of conservative septoplasty, in distinction
to the more aggressive submucous resection, is well tolerated and
normal nasal and midface development can be expected. The al-
ternative of continued observation in the face of nasal obstruction
Septoplasty and Rhinoplasty in Pediatric Group 169

FIGURE 1.
The nasal septum with growth centers shaded.

is associated with unacceptable aberrant growth patterns as well


as unnecessary discomfort for the patient.
More specifically, our indication for septoplasty in the child is
whenever complete nasal obstruction exists, regardless of age. Ev-
ery effort is made to use cartilage-sparing techniques, including re-
shaping rather than resecting. We believe that chronic and com-
plete nasal obstruction can lead to midface growth retardation and
therefore, we restore a functional nasal airway before the onset of
pubertal growth. Every attempt is made to avoid resection of carti-
laginous septum but when such maneuvers are needed, the carti-
lage is reshaped and returned as a free graft. This is the most ag-
gressive septal surgery that we perform on young children and it
may have subtle effects on facial morphology. When incomplete
nasal obstruction exists, we use more conservative algorithms, in-
cluding a delay in intervention until after puberty. Newer endo-
scopic techniques have allowed mild to moderate deviations to be
S.S. Park and C.W. Gross

addressed in this age group. These techniques are particularly


suited for the isolated septal spur.
Rhinoplasty in the pediatric age group falls into two different
groups: either repair of the acutely traumatized nose or elective sur-
gery requiring primary intervention through previously unviolated
tissues. Regardless of age, the acutely displaced nasal bones require
an accurate closed reduction, recognizing that this may require gen-
eral anesthesia or completion osteotomies if a "greenstick" fracture
exists and full mobilization is hindered. In these circumstances,
2-mm percutaneous osteotomies are ideally suited to complete the
fracture with minimal soft tissue disruption.
Cosmetic rhinoplasty has a lesser role in the pediatric age
group, although some circumstances warrant surgery for the over-
all benefit of the child. Psychological considerations have a major
impact during this assessment. Eighty-seven percent of the adult
nasal growth is achieved by the age of 12 for girls and age 15 for
24
b o y s . Permitting this pubertal growth to be completed before sur-
gery will allow more confidence during intervention and with the
final outcome. General concepts include extreme conservatism
with preference toward reorienting cartilages rather than reshap-
ing, with resecting remaining as a last resort. The twisted nose oc-
casionally can be repaired with lateral osteotomies alone, avoid-
ing medial osteotomies and minimizing dorsal nasal trauma. Ex-
treme caution is exercised with any profile reduction, particularly
because the dorsal cartilaginous septum represents an active
growth center.
Our timing for tip rhinoplasty or dorsal modification is a mini-
mum of age 12 years for girls and 15 years for boys. Additionally,
other variables can be factored in, such as overall body develop-
ment and growth relative to their parents. Narrowing or refinement
of the nasal tip and reduction of a prominent bony/cartilaginous
dorsum are common requests from pediatric patients and their par-
ents but are best delayed until the appropriate age. Common ma-
neuvers such as the complete strip or vertical dome division are
avoided until complete nasal growth has occurred. Cartilage spar-
ing techniques such as interdomal suturing and camouflage graft-
ing can be performed at an earlier time. All nasal, septal, and si-
nus surgeries in the pediatric age group should include thorough
preoperative counseling that includes a discussion on potential
growth disturbances as well as progressive changes during the
child's maturation. The usual concerns pertaining to psychosocial
motivations in adult cosmetic surgery patients are amplified in
children in whom motivations are intimately tied with peer pres-
Septoplasty and Rhinoplasty in Pediatric Group 171

sures. Not infrequently, parents will appear to be rational and prac-


tical; however, their perception and expectations are seen through
their child's verbal complaints. The parents' emotional investment
and lability should not be underestimated.
Congenital malformations are an exception, when obvious de-
formity is expected to continue into adult life. The cleft lip nasal
deformity is an example in which we aggressively modify lower
lateral cartilage position during the initial lip repair (age 2 to 3
25
m o n t h s ] . The goal is to reorient the intermediate and lateral crura
and attempt to guide its future growth toward improved tip sym-
metry.
There is more flexibility with conservative maneuvers that do
not involve resection of nasal structural skeleton. Small changes
such as straightening the nose or smoothing subtle bony irregulari-
ties can be performed more liberally. The endoscopic rhinoplasty
drill is ideally suited for such minor modifications of the bony
pyramid while avoiding osteotomies.

TECHNIQUE
There is an array of techniques for septoplasty in the pediatric age
group that maximize preservation of tissues. The closed reduction
of a septal fracture is performed in the acute setting whenever ap-
propriate. Silastic septal splints may be necessary to maintain
structural support to the fractured septum. The "septal swing" is
another technique of improving nasal airway while avoiding ex-
cessive resection of the quadrilateral cartilage. In this technique,
the mucoperichondrial flap is elevated on one side and the bony
cartilaginous junction is disarticulated posteriorly and inferiorly.
At times, a "boomerang" strip of cartilage is excised from the pos-
terior and inferior borders to allow more complete mobilization of
the cartilaginous septum. This is always necessary when a dislo-
cation and subluxation of cartilage over bone has occurred. The
septal cartilage remains hinged along its dorsal aspect to the up-
per lateral cartilages and the nasal bones. The septum will now
come to rest in the midline and can be sewn in place with fixation
to the periosteum of the nasal spine. Septal spurs and longitudinal
fractures require resection and are usually done under direct vi-
sion with bilateral flap elevation. When the cartilage has intrinsic
deviations and a bowed configuration, we prefer to alter the shape
rather than resect. Partial-thickness or full-thickness incisions on
the concave side of the cartilage will alter the intrinsic forces and
allow the cartilage to straighten. This scoring serves as relaxing in-
172 S.S. Park and C.W. Gross

cisions, allowing the concavity to spring back. It is important to


leave the contralateral mucoperichondrial flap attached to the car-
tilage, particularly when performing full-thickness incisions; oth-
erwise, the small islands of cartilage will become devitalized and
risk subsequent resorption. Furthermore, the perichondrium at-
tached to the convex side will, itself, tend to straighten the carti-
laginous deformity. The need for cartilaginous incisions must be
anticipated prior to flap elevation. On occasion, a sufficient dis-
crepancy in flap size will contribute to the septal deflection. Un-
der these circumstances, bilateral flap elevation alone may allow
the cartilage to straighten.
Advances in biomedical engineering technology have made
significant contributions to nasal surgery, particularly through the
fiberoptic cable and the tremendous illumination and detail that
are now available. Simultaneously, powered instrumentation has
supplemented the concept of minimal access surgery by allowing
aggressive yet precise removal of tissues. Minimizing soft tissue
disruption is the essence in pediatric nasal surgery. The endoscopic
drill and soft tissue shaver have allowed a target-specific approach
to nasal pathology.
Endoscopic septoplasty is ideally suited for focal areas that re-
quire resection, such as an obstructing spur hindering endoscopic
sinus surgery. A standard, vertical, mucoperichondrial incision is
made 2 cm anterior to the spur. The hemitransfixion incision and
elevation of perichondrium along the caudal septal strut are no
longer necessary. Elevation is done around the spur with direct vi-
sualization through the O-degree and 30-degree endoscopes. The
endoscopic burr has been developed to allow removal of cartilage

FIGURE 2.
Endoscopic burr [Linvatec, 1 1 3 1 1 Concept Boulevard, Largo, FL 33773).
Burrs are 4 mm in outer diameter and the distal tip is circumferentially
protected by the outer sheath.
Septoplasty and Rhinoplasty in Pediatric Group 173

FIGURE 3.
A, lateral view of endoscopic burr position to reduce a septal spur. B, an-
terior view demonstrating retained septal cartilage continuity.

and bone while protecting the surrounding soft tissues from the
cutting surfaces (Fig 2). The drill is inserted under the flap and used
to reduce the cartilaginous or bony septal spur under direct vision
(Fig 3). Usually a partial reduction is needed before one can safely
dissect the flap off the posterior surface of the spur. The end point
is when the spur is reduced and access achieved. The contralat-
eral mucoperichondrium and a thin strut of cartilage in the area of
the spur remain, maintaining septal continuity.
Rhinoplasty in the pediatric age group is performed selectively,
and only rarely is native tissue resected. Aggressive changes such
as a dome division or a dorsal hump reduction through osteoto-
mies are not performed until pubertal growth is completed. Once
that has occurred, a standard intercartilaginous incision provides
the usual access to the nasal dorsum, and the profile is modified
with a Rubin osteotome, followed by a sharp resection of the car-
tilaginous dorsum, and finally lateral osteotomies. More subtle
asymmetries and contoured deformities can be addressed at an ear-
lier age with the endoscopic rhinoplasty drill (Fig 4). Access is
174 S.S. Park and C.W. Gross

FIGURE 4.
Lateral view of endoscopic burr used to modify the nasal bony dorsum.

achieved through a conventional endonasal approach; however,


sufficient undermining is performed to accommodate the 4-mm
outer diameter drill. Once the drill is situated under the perios-
teum of the nasal bones, it is lightly applied to the bony promi-
nence. Completion osteotomies are rarely necessary. Aggressive
modifications are not suited for the endoscopic technique because
the change in shape is limited to the thickness of the bones. Re-
cently, the burr has been routinely used to round bony edges after
a standard osteotomy. Instead of the shearing forces of the rasp and
the risk of inadvertent bony avulsion, the burr is gently applied to
smooth the bony edges. One should irrigate under the soft tissue
envelope to remove the bone dust that remains.
Refinement of the nasal tip in the pediatric age group requires
an even more conservative approach than conventional tip surgery.
Subtle changes can be achieved with the endonasal cartilage-
splitting approach, with a resection of the cephalic margin of the
lateral crura. The effects of this maneuver continue beyond 1 year
and deliberate patience by the family and surgeon are paramount.
Refinement of the wide or trapezoidal tip is achieved through the
horizontal transdomal mattress sutures, rather than the more ag-
Septoplasty and Rhinoplasty in Pediatric Group 175

26
gressive dome divisions and cartilage resections. These sutures
can be placed through the delivery or open approaches. A 4.0 clear
PDS (Ethicon, Somerville, New Jersey) suture is used for this, al-
though permanent nylon or polypropylene sutures can be used as
well. The intention is to reorient and reshape the tip cartilages
rather than remove them, which will allow continued growth and
development.
For closure, the mucoperichondrial flaps from the septoplasty
are reapposed with a through-and-through "quilting" technique
with an absorbable catgut suture. Sufficient flap apposition and
septal support can be achieved through this technique, obviating
the need for septal splints or intranasal packing. Only with rare
exception is intranasal packing used for the pediatric septoplasty.
The cartilage splitting incision is closed with 5.0 gut sutures in
simple stitches. Care is taken to use extremely small bites and avoid
grasping the lateral crura. Aggressive sutures here will cause some
distortion, particularly along the alar rim. When closing the open
rhinoplasty, 6.0 fast-absorbing gut sutures are used along the mar-
ginal incision with the same attention to placing small bites. The
columellar flap is similarly closed with simple stitches at each of
the corners. The rhinoplasty dressing is with V2-inch brown paper
tape alone. It serves to apply diffuse pressure over the nose and
minimize edema and hematoma formation. The nasal cast is usu-
ally not necessary unless bilateral osteotomies have been created.

REPRESENTATIVE CASE
A 19-year-old man was interested in a rhinoplasty that would re-
duce his nasal "hump" (Fig 5). Examination revealed a mild bony
prominence but with a subtle supratip depression and marked
blunting of the nasal frontal angle. Resection of the bony dorsum
alone would result in complete loss of the root of the nose and an
unnatural profile. We elected to augment the supratip area with a
septal cartilage onlay graft and only minimally reduce the bony na-
sal dorsum. This subtle contouring of the nasal bones and nasion
was achieved with the endoscopic rhinoplasty burr. The bony dor-
sum was lowered only slightly to match the augmented cartilagi-
nous dorsum, leaving the illusion that the hump had been resected
while preserving the nasal frontal angle (Fig 6).

CONCLUSION
Advances in septoplasty and rhinoplasty in the pediatric age group
have allowed us to revisit the concept that nasal surgery in chil-
176 S.S. Park and C.W. Gross

FIGURE 5.
Preoperative view of a 19-year-old man requesting resection of dorsal
hump. A, anterior view. B, lateral view.
Septoplasty and Rhinoplasty in Pediatric Group

FIGURE 6.
S i x months postoperatively after supratip augmentation and slight reduc-
tion of bony dorsum with the rhinoplasty burr. A, anterior view. B, lateral
view.
178 S.S. Park and C.W. Gross

dren is to be avoided at all costs. Powered instrumentation has al-


lowed a target-specific approach through minimal access and mini-
mal soft tissue disruption.

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ing, and technique, in Sykes JM, Senders CW (eds): Facial-Plastic Sur-
gery Clinics 4 ( 3 ) : 3 4 3 - 3 5 0 , Philadelphia, WB Saunders, 1996.
26. Tardy ME, Heinrich JA, Lindbeck EO: Refinement of the nasal tip in
Simons RL (ed): Facial Plastic Surgery Clinics 2 ( 4 ) : 4 5 9 - 4 7 6 , Philadel-
phia, WB Saunders, 1 9 9 4 .
C H A P T E R 10
Screening for Hearing
Loss in Neonates: Where
Do We Stand?
Yvonne S. Sininger, Ph.D.
Director, Children's Auditory Research and Evaluation Center, House Ear
Institute, Los Angeles, California

T he topic of this chapter is the current status of screening for


hearing loss in newborns. Information currently available that
has led to the consensus that universal newborn hearing screening
(NHS) is appropriate and timely will be discussed. This topic has
a long and complicated history that will be detailed. Next the is-
sues and principles of epidemiology surrounding this topic will be
highlighted. The pros, cons, and details of using auditory brain
stem response (ABR) and otoacoustic emissions (OAE) as screen-
ing tools will be discussed, along with combination protocols and
principles of screening tool selection. Finally, the status of infant
hearing screening in the individual states and the current political
motion in the United States federal government as of this writing
(October 1997) will be outlined.
Accurate, objective, physiologic measures of hearing that can
be applied to neonates have been available for more than 20 years.
1
In 1 9 7 0 , the ABR was first described, and the obvious use of this
technique for assessment of hearing in newborns was soon
2-5 6 7
explored and found to be v i a b l e . Later, otoacoustic emissions '
were described, and the clinical and scientific community had the
same reaction: as soon as the technique was found to be valid, the
potential for use of this objective measure of auditory function in
8,9
assessment of newborns was explored and found fruitful.
Despite the existence of two very good assessment tools, universal
identification of hearing impairment in newborns is a reality in
only a handful of states. The average age of identification of hear-
ing loss in children, depending on severity, is still between 12 and
9
Advances in Otolaryngology-Head and Neck Surgery , vol.12
c
1 9 9 8 , Mosby, Inc.
182 Y.S. Sininger

24 months. Unilateral and mild losses may not be identified until


children reach school age.
Children with hearing loss who receive early intervention can
achieve near-normal communication skills. Some groups of profes-
sionals and individuals have been reluctant to endorse universal
NHS without more scientific evidence that early intervention for
infants with hearing loss leads to significantly better outcomes for
these children. Controversy over whether the screening tools avail-
able had adequate sensitivity and specificity and were inexpensive
10
also dampened enthusiasm in some s k e p t i c s . The irony is that it
is virtually impossible to identify hearing impairment very early
in a significant number of infants without early detection programs.
It follows that, without a significant number of infants with early
identification and remediation, it has been impossible to demon-
strate the benefits of such early intervention on language and com-
munication skills. This cycle may have been broken finally because
of the hard work and dedication of Marion Downs and her
colleagues in Colorado, which has led to recent legislation for the
adoption of a state-wide universal hearing screening program.
Along with that program came the long-awaited research compar-
ing infants who receive early intervention with those for whom in-
tervention is delayed. Dr. Christine Yoshinaga-Itano, chair of the
Speech, Language, and Hearing Sciences Department of the Uni-
versity of Colorado at Boulder, working in conjunction with the
Marion Downs National Center for Infant Hearing, with assistance
from the National Institutes of Health and Maternal and Child
Health, has studied and followed up newborns with hearing loss.
Dr. Yoshinaga-Itano's data are submitted for publication, but a pre-
liminary report has compared 72 children whose treatment (hear-
ing aids and appropriate educational intervention) began before 6
months of age with those (n = 78) whose intervention, for a vari-
11
ety of reasons, began after 6 months of a g e . The children were
followed past 3 years of life. Those with intervention before 6
months have an average language quotient of 8 5 . 5 , meaning that
they fall in the 85th percentile for language compared to normally
hearing children. Those identified later have language ability sig-
nificantly below the early-identified children. Furthermore, this re-
sult is found regardless of age at data collection. That is, the posi-
tive benefits on language and communication gained through early
remediation remain past 3 years of age. Another way of saying this
is that the detriment to language and communication imposed by
late (even just 6 months) remediation remains for an indefinite pe-
riod. Positive effects of early remediation are found regardless of
Screening for Hearing Loss in Neonates 183

until degree of hearing loss (near-normal language is found in children


with profound as well as mild loss), cognitive delay or multiple
handicap, gender, level of parent education, financial status, or
mode (manual or oral) of communication. Finally, the information
that many of us have had in anecdotal form is available as a con-
trolled scientific study, and the real data are more convincing than
we could have imagined. Early identification of hearing loss with
appropriate intervention will achieve greatly improved communi-
cation outcomes for children.
Perhaps due to the release of the above data and to more evi-
dence of the feasibility (see later sections), enthusiasm for such uni-
versal screening programs has recently escalated, and it appears
that the dam is about to break. To understand how and why this is
happening, it is important to understand the history of NHS in the
corn- United States.

HISTORY
More than 30 years has passed since the first report of a program for
12
newborn hearing assessment. Earliest techniques used loud
noisemakers and systematic observation of infant startle or arousal.
These initial, valiant efforts to identify hearing loss in the newborn
period were flawed by poor stimulus control, lack of specificity (ear
or hearing level), and the subjectivity in detection of an infant "re-
sponse." In addition, these programs were time and labor intensive.

CRIB-O-GRAM
loss. In the 70s, the Crib-o-Gram was developed by Simmons and col-
13
l e a g u e s in an attempt to automate the detection of startle with
motion sensors attached to the infant's crib. Sounds were presented
to the sleeping infant via loud speakers and movement on the part
of the baby that was coincident with the sound was assumed to be
response to the sound. All activity was recorded and stored in a
computer. Crib-o-Gram assessments could take between 1 and 24
hours to complete and although attempts had been made to address
the issue of objectivity, problems with time, cost, response habitu-
ation, and false positive identification of hearing loss as high as
3 2 % using the Crib-o-Gram made this technology infeasible for
1 4 , 1 5
widespread use.

JOINT COMMITTEE ON INFANT HEARING AND HIGH RISK


REGISTER
In 1 9 6 9 , a committee was formed to make recommendations regard-
ing screening for hearing loss in newborns. This group, which has
Y.S. Sininger

become known as the Joint Committee on Infant Hearing (JCIH),


was composed of representatives from the American Speech and
Hearing Association (now the American Speech-Language-Hearing
Association), the Academy of Pediatrics, and the Academy of Oph-
thalmology and Otolaryngology (now the American Academy of
Otolaryngology, Head and Neck Surgery [AAOHNS]). In 1972, this
committee published the first list of neonatal factors that were as-
sociated with increased risk of hearing loss. This high-risk register
(HRR) for hearing loss in infants contained five factors, including
(1) family history of hearing loss; (2) rubella or other nonbacterial
intrauterine fetal infection (e.g., cytomegalovirus, herpes); (3) de-
fects of the ear, nose, or throat; (4) low birth weight (< 1,500 g);
and (5) bilirubin greater than 20 mg/100 mL serum. The commit-
tee recommended that screening for hearing loss would be more
efficient if limited to infants with these factors.
By definition, any procedure that effectively reduces the num-
ber of infants who need a full audiologic evaluation can be con-
sidered screening. Consequently, just determining which infants
are at risk is a type of screening procedure. The rationale for using
the HRR was to reduce the number of infants for screening, thus
decreasing cost. The prevalence of hearing loss (including mild to
moderate and unilateral loss) in the newborn population as a whole
is 3 to 6 in 1,000, whereas the prevalence of hearing loss among
16
those with high-risk factors is approximately 30 to 50 in 1 , 0 0 0 .
The rationale for the use of the HRR is that the number of infants
who require screening is dramatically reduced, assuming only
17
about 1 0 % of all newborns have risk factors.
In 1 9 7 2 , when no rapid, accurate, objective assessment tools
were available, reducing the number of infants in the pool for au-
diologic screening was wise and prudent. Time, however, has
shown that, even as the list of factors on the HRR has been
expanded and refined, close to half of all neonates with significant
hearing loss have no risk factors and will be missed by a screening
1 8 - 2 0
mechanism that concentrates on the HRR a l o n e . This fact has
led to a call for screening of all infants, or "universal NHS." Be-
fore universal NHS can be feasible, however, screening techniques
must be shown to be fast and accurate.
Until universal hearing loss detection in the neonatal period is
achieved, identification of risk factors for hearing loss will still be
important. The JCIH, which currently includes the original mem-
bers as well as the American Academy of Audiology, the Council
for Education of the Deaf (including Alexander Graham Bell Asso-
ciation for the Deaf), and the Directors of Speech and Hearing Pro-
TABLE 1.
Risk Factors for Hearing Loss: 1 9 9 4 Position Statement of the Joint
Committee on Infant Hearing

Infants
Neonates Infants Requiring Periodic
(Birth to 28 days) (29 days-3 years) Monitoring
Family history of Concern regarding Family history of
hereditary childhood hearing, speech, hereditary childhood
sensorineural hearing language, or sensorineural hearing
loss developmental delay loss
In utero infection Bacterial meningitis In utero infection
(cytomegalovirus, and/or other (cytomegalovirus,
rubella, syphilis, herpes, infections associated rubella, syphilis,
and toxoplasmosis) with sensorineural herpes, and
hearing loss toxoplasmosis)
Craniofacial anomalies Head trauma (loss of Neurofibromatosis type
including pinna and ear consciousness) or II and
canal skull fracture neuro-degenerative
disorders
Birth weight < 1 , 5 0 0 g Stigmata of syndromes Recurrent or persistent
known to include otitis media with
sensorineural or effusion
conductive hearing
loss
Hyperbilirubinemia at Ototoxic medications Anatomic deformities
serum levels requiring used in multiple and other disorders
exchange transfusion courses or in that affect eustacian
combination with tube function
loop diuretics
Ototoxic medications Recurrent or persistent Neurodegenerative
used in multiple courses otitis media with disorders
or in combination with effusion for at least 3
loop diuretics months
Bacterial meningitis
APGAR scores of 0 - 1 (1
minute) or 0 - 6 (5
minutes).
Mechanical ventilation >
10 days
Stigma associated with
syndromes known to
include sensorineural
hearing loss
186 Y.S. Sininger

grams in State Health and Welfare Agencies, has issued subsequent


position statements in 1982, 1 9 9 0 , and 1 9 9 4 . The most recent state-
2 1
ment, published in 1 9 9 4 , continues to recognize the importance
of the HRR but this statement also "endorses the concept of uni-
versal hearing screening." The 1994 statement updates the list of
indicators associated with hearing loss in neonates to 10 (Table 1)
and adds a list appropriate for infants (29 days to 3 years of age).

ABR
The 1980s brought about a flurry of activity from scientists and cli-
nicians on the use of ABR in the newborn nursery, usually within
the newborn intensive care unit (NICU), with infants having some
or many of the high-risk factors. Automatic detection of ABR had
not yet been introduced; standard ABR measures were evaluated
visually for response detection by audiologists, physicians, and sci-
entists. Comparisons with behavioral observation audiometry
(BOA) found the ABR to be much more sensitive to hearing disor-
14
ders and more specific (fewer false positives). Visual reinforce-
ment audiometry (VRA) is far superior to BOA for detection of hear-
ing loss but cannot reveal accurate hearing estimates in nonrisk in-
fants younger than about 6 months of age and in NICU graduates
2 2 , 23
until about 8 months of a g e .
A summary of ABR studies from the early to mid-1980s of in-
fants from high risk populations found that the technique would
fail about 1 5 % of the infants, whereas follow-up of these infants
24
determined that 3 . 5 % had sensorineural hearing l o s s . This con-
stituted a significant improvement over behavioral assessment, but
the general impression was that ABR was still too time consuming
and costly to perform on all newborns.

FEDERAL ACTIVITY AND NIH-FUNDED SCREENING PROJECT


Among the first recognitions at the national level of the importance
of early identification of hearing loss came with the 1 9 9 0 Healthy
People 2000 initiative, which included in its goals the reduction
of the average age at which children with hearing loss were iden-
2 5
tified to under 12 months by the year 20 0 0 . This was an impor-
tant milestone in the history of the movement toward universal
NHS in that it set attainable goals and drew attention to the issue.
The National Institute on Deafness and Other Communication
Disorders (NIDCD) was established in 1988. For the first time, the
term "deafness" was a part of the NIH. One of the officers of that
institute, Dr. Maureen Hannley, now director of research with the
AAO-HNS, began working on a proposal to call for research in the
Screening for Hearing Loss in Neonates 187

area of newborn screening, specifically a project to compare and


evaluate ABR and OAE as techniques for NHS. In April of 1 9 9 3 ,
the NIDCD awarded a 5-year project entitled "Identification of Neo-
natal Hearing Impairment" to Dr. Susan Norton of the University
of Washington, Seattle. This multicenter consortium project col-
laborated with laboratories and coinvestigators (Pis) from Boys-
town National Research Hospital, University of Kansas Medical
Center, Women's and Infants' Hospital in Rhode Island, University
of Southern California, and House Ear Institute. The study evalu-
ated 4,800 infants from the NICU and 2,400 from the normal well-
baby nursery using two types of OAE: distortion-product evoked
and transient-evoked, as well as automated ABR measures in both
ears. A significant subset of the NICU infants were reassessed for
hearing thresholds by behavioral means at 6 to 8 months of age,
regardless of outcome of the neonatal screening to evaluate the true
sensitivity and specificity of the screening tools.
Data collection on this project will be completed in October
1997. Some preliminary findings will be reviewed in the section
of techniques. This project represented an important investment by
the NIDCD under Dr. James Snow, in the information necessary to
promote NHS, namely the exact operating characteristics of the two
most viable and appropriate screening tools, ABR and OAE. These
data will be available within the next year.

NIH CONSENSUS DEVELOPMENT CONFERENCE


The NIH uses a mechanism called the "Consensus Development
Conference" to help bring clarity to important health-related issues,
especially when controversy exists. The conference enlists speak-
ers knowledgeable in a health-related area to give presentations and
appoints a panel of experts with a broad base of interest related to
the area to summarize the input and form a consensus on major
issues. In March 1 9 9 3 , the NIDCD convened such a conference on
the topic of "Early Identification of Hearing Impairment in Infants
and Young Children." The panel concluded the following: (1) in-
fants in NICUs should be screened for hearing loss before discharge
from the hospital; (2) all infants should be screened before 3
months of age; (3) a recommended model for screening would have
two stages, beginning with an OAE with failures on stage one fol-
lowed by an ABR; (4) comprehensive intervention and manage-
ment must be included in any screening program; (5) surveillance
of hearing should continue throughout childhood; (6) primary care-
givers and health care providers should receive education regard-
ing early signs of hearing loss.
188 Y.S. Sininger

Although the panel recommended screening before 3 months


of age, they state that in the most efficient model, infants would be
screened before leaving the birth hospital. They also state that other
models for screening, such as a primary screening with ABR, are
acceptable especially where such screening programs are already
in existence. In addition, the panel called for continued research
on the efficacy of early identification and intervention and on com-
parison of screening techniques. The recommendations of this
panel have had a significant impact upon the movement toward
universal NHS. This was the first national endorsement of screen-
ing of all infants. Also, several large scale studies addressing the
research questions mentioned have subsequently been funded by
the NIDCD. However, there has also been severe questioning of uni-
versal infant screening that was inspired by the Consensus Confer-
10
ence. The most vocal opposition came from Bess and P a r a d i s e in
an editorial published soon after the Consensus Conference in the
journal Pediatrics.
Bess and Paradise recognized the profound effects of early hear-
ing loss on communication ability of children. However, they op-
pose universal newborn screening and argued that the recommen-
dations of the NIH Consensus Conference were ill advised and in
their words, universal screening is "not simple, not risk free, not
necessarily beneficial and not presently justified." They argued that
the OAE technique would overidentify hearing loss in newborns
and consequently lead to expensive follow-up testing in a large
number of infants if applied universally. They further argued that
no convincing empirical evidence exists to prove that early inter-
vention leads to improved outcomes such as improved communi-
cation ability or academic performance.
The article by Bess and Paradise was a setback in the forward
motion of the efforts to implement universal NHS programs in the
United States. Northern and Hayes are two prominent pediatric au-
diologists with many years of experience with early identification.
They argued convincingly that Bess and Paradise's conclusions on
the number of false positives that would be incurred by the NIH's
recommended protocol were based on inappropriate numbers of
the percentage of failures that could be expected, as well as a ba-
sic underestimation of the percentage of infants who will actually
demonstrate hearing loss when mild and moderate losses are in-
16
cluded.
Other data needed to refute the arguments of Bess and Para-
dise, for example that of Yoshinaga-Itano, have become available
subsequent to their publication. More accurate estimates of the fail-
Screening for Hearing Loss in Neonates 189

ure rates of ABR and OAE testing will be given in subsequent sec-
tions of this manuscript. Although the publication of their argu-
ments in Pediatrics may have done a great deal to convince pedia-
tricians against the need for universal screening, it has led to a
flurry of publication of important data and perhaps helped to unify
and intensify the efforts of groups who endorse universal NHS.

PRINCIPLES OF SCREENING
The World Health Organization has established a set of principles
for screening for any disease process that can be used to justify the
effort. These principles include the following: (1) Is the burden cre-
ated by the problem (disease) significant? (2) Is effective treatment
for the problem available? (3) Is the performance of the screening
device(s) adequate? (4) Is there evidence that early identification
and treatment improve outcomes over the alternative of waiting?
(5) Have costs been considered and evaluated? (6) Are there suffi-
cient resources and appropriate strategies to implement screening?
This section will discuss the ways in which the third principle
can be evaluated. Much of the controversy surrounding the imple-
mentation of NHS involves the adequacy of our screening tools.
However, based on current studies and application of basic prin-
ciples used to evaluate performance, it can be shown that adequate
screening tools are available for NHS.

TARGET DISORDER
Screening for a disorder first requires an exact specification of the
target disorder. Hearing thresholds lie on a continuum from nor-
mal to profound loss. In addition, hearing loss can differ by fre-
quency regions, can be conductive, sensory, or neural, and can be
different in the two ears. The type, degree, and configuration of
hearing loss that is targeted will influence the incidence of the dis-
order. Mild, unilateral conductive loss, for example, is much more
common than profound, bilateral sensory loss. The performance of
the screening tests relative to detection of the disease will also be
influenced by the defined target disorder. For example, it is much
easier and takes less time to screen for hearing loss using a high-
level ABR stimulus that will be sensitive to a moderate or severe
loss than to use a low-level stimulus in an effort to detect a mild
hearing loss.
A basic consensus on the target disorder for NHS has been
reached with surprisingly little controversy. The target designated
in the NIDCD-funded study is mild (30 to 40 dB), unilateral, or bi-
lateral hearing loss within the speech frequencies (500-4,000 Hz)
190 Y.S. Sininger

regardless of type (conductive or sensorineural). Many publica-


tions regarding screening fail to state the exact target disorder but,
when not explicitly stated, this definition is generally assumed.
This definition of mild and even unilateral loss as a target makes an
important statement in that it recognizes the negative educational
26
consequences that can accompany transient c o n d u c t i v e and uni-
27
l a t e r a l hearing loss.

OPERATING CHARACTERISTICS
Once the target disorder is defined, the true presence or absence of
the disorder needs to be determined in some acceptable way. In
the case of hearing loss, the "gold standard" is usually a behav-
ioral measure of hearing that is administered sometime after the
newborn period, inasmuch as such tests are not accurate in infants
younger than 6 to 8 months of age. In some instances, a new test
will be compared to a more established procedure as a gold stan-
dard. This was the case in initial evaluations of OAE as a screener,
using ABR as a gold standard. There are four possible combina-
tions of results of the screening test and gold standard. The out-
comes are true positive (screening test positive and disorder is
present), false positive (screening test positive and disorder is ab-
sent), false negative (screening test negative and disorder is
present), and true negative (screening test negative and disorder is
absent).
Operating characteristics essentially compare the outcome of
the screening device and the gold standard test in some meaning-
ful way. Sensitivity defines the ability of the test to correctly
identify the disorder. In this case, sensitivity of a screening test
for newborn hearing loss is defined as the percentage of infants
with hearing loss who have a positive test. Sensitivity is com-
puted as the true positive divided by true positive plus false
negative.
It is important to note that to determine false negative rate, all
screened individuals must have the gold standard test. For
example, all infants screened, whether they pass or fail the screen-
ing test, would need to have a behavioral evaluation of hearing.
Because of the enormous cost of following up with a large number
of infants for 6 to 8 months or more, most studies merely assume
that all infants who pass the initial screen do not have hearing loss.
This assumption is invalid, and test sensitivity cannot be stated
explicitly unless the appropriate follow-up is done. Because of a
lack of follow-up on all infants, many studies do not report test
sensitivity.
Screening for Hearing Loss in Neonates 191

Specificity is the ability of a screening test to properly rule out


the disorder. In this case, specificity is the percentage of infants
with normal hearing who pass the test (have a negative finding on
the screening test). Specificity is computed as the true negative di-
vided by true negative plus false positive.
Finally, the positive predictive value of a test looks at how well
a test can predict the disease. This is the percentage of infants who
test positive and have hearing loss. This is computed as the true
positive divided by true positive plus false positive.
Determining the sensitivity, specificity, and predictive value of
a screening test requires specification of the exact testing protocol.
For example, if a response is judged as present or absent based on
some criterion, such as a minimum amplitude of the ABR or signal-
to-noise ratio (SNR) on the OAE, the exact criterion must be speci-
fied before performance criteria can be computed. These perfor-
mance criteria change with response criteria. For example, if one
demanded a very high SNR as criterion for presence of an OAE
(e.g., 1 0 - d B SNR overall), then sensitivity would be very high be-
cause every infant with hearing loss would fail. However, specific-
ity would go down because many infants with normal hearing
would also fail this strict criterion. The number of times a test is
performed or the number of stages of testing must also be taken
into consideration when evaluating performance characteristics.
Almost any test will show improved performance by repeating the
test in infants who fail the first stage. The trade-off comes in in-
creased test time and cost for multistaged test protocols. When
comparing screening methodologies, one must take all of these
variables into consideration. There will not be one set of perfor-
mance characteristics for ABR and one for OAE because of the
number of variables that can be manipulated to come up with the
performance. For a complete overview of development of test strat-
2 8
egy, see Hyde et a l .
One of the major costs of an NHS program is the cost of
follow-up on an infant who failed the initial screening. If a test de-
vice has a high false positive rate, high cost will be incurred from
follow-up on infants who do not have hearing loss. Other draw-
backs of high false positive rate include the unnecessary alarm
caused to the families of those who fail, as well as the destruction
of confidence, especially of other professionals, in the screening
process. This is akin to crying "wolf" too often. Because true sen-
sitivity and specificity rates are often not available, many use the
"pass rate" of a screening test as the next best indicator of test per-
formance. Because we know that about 3% of high-risk and 0 . 3 %
192 Y.S. Sininger

of all infants should fail a screening test because they have hear-
ing loss, the more that failure rates exceed this number, the less
value the test is seen as having. In other words, a test that can pass
only 7 0 % or 8 0 % of newborns will have an excessive false posi-
tive rate. Adequate screening tests today should have a pass rate
of more than 9 0 % to 9 5 % .

OAES IN INFANT SCREENING


Otoacoustic emissions are low-amplitude acoustic events that can
be recorded in the ear canal a few milliseconds after the presenta-
tion of a sound and the processing of that sound by the cochlea
29
(see S i n i n g e r for an overview of OAEs). Otoacoustic emissions
are thought to be reflections of the active mechanical action of the
outer hair cell (OHC) that is initiated by basilar membrane deflec-
3 0 , 31
tions in response to soft s o u n d s . The energy produced at the
OHC transmitted to the basilar membrane, aiding in detection of
soft sounds, is transmitted to the cochlear fluids and, in turn, drives
the stapes, ossicular chain, and tympanic membrane in reverse,
leading to a production of sound in the ear canal that is detected
as an OAE by sensitive microphones. This active process is also
nonlinear and produces harmonic distortion. When two pure tones
are presented to the ear, the cochlea will produce energy at several
other frequencies that are harmonically related to the first two. The
most prominent of these is a tone with a frequency equal to two
times the first tone minus the second (2fl - f2). This is known as
a distortion-product OAE, or DPOAE, and can also be measured
with ear canal microphones.
Otoacoustic emissions are preneural events that exist in the ab-
32
sence of any innervation. Although the amplitude of the emis-
33
sion can be altered by stimulation of the olivo-cochlear b u n d l e ,
this innervation is not a prerequisite for the presence of an OAE.
Otoacoustic emissions that are most commonly used are either
DPOAEs or transient-evoked OAEs (TEOAEs). The latter are elic-
ited by short-duration sounds (transients), usually a click, and the
microphone-sampled OAE is measured a few milliseconds later.
Because a click contains a broad range of frequencies, a frequency
(spectral) analysis of the OAE can reveal normal and abnormal ar-
eas of cochlear processing. Unlike the click-evoked ABR, the
TEOAE response itself can contain frequency-specific information.
The DPOAE can be measured eliciting tones to sample processing
in different frequency regions of the cochlea. Both TEOAEs and
DPOAEs in neonates suffer from severe noise contamination for re-
Screening for Hearing Loss in Neonates 193

sponses below about 1 , 5 0 0 Hz or 1 , 0 0 0 Hz, and assessment of those


frequency regions in newborns is not yet feasible with OAEs.
Cochlear amplification by means of the OHC is only necessary
for processing of soft sounds, and true OAEs are only present for
sounds under about 50 dB hearing level (or 8 0 - 8 5 dB sound pres-
sure level [SPL]). Consequently, the presence of an OAE generally
indicates that the cochlea is processing soft sounds and that a hear-
ing loss, if present, is less than 30 dB to 40 dB. This makes the
OAE well qualified as a screening device for mild hearing loss but
not as an indicator of hearing level for moderate or severe loss. Be-
8 9 34
cause OAEs can be recorded in the vast majority of n e w b o r n s , ' '
they have received much attention as a potential screening tool for
29
neonatal hearing l o s s .
Amplitude of the infant OAE varies considerably across sub-
jects. Signal processing, such as averaging and estimates of record-
ing noise versus signal strength, allow the detection of OAEs with
amplitudes as small as about —10 dB SPL. Amplitude of infant
35 36
OAEs are generally larger than those of adults, ' and transient
OAEs can reach an amplitude of 30 dB SPL or more. However, the
response must be transmitted through the middle ear to be
recorded. This can be a limitation in the newborn population that
may have unresolved mesenchyme or amniotic fluid in the middle
ear, or early otitis media or residual debris from the birth process
in the ear canal. Several studies have found reduced OAE ampli-
tude and a higher rate of screening failure in infants tested fewer
37, 38
than 48 hours after b i r t h , when these complications are most
likely to occur. Others have shown a clear correspondence between
39,40
tympanic membrane mobility and OAE response a m p l i t u d e .
Contamination from room and breathing noise can also interfere
with OAE recordings from newborns. Even though the probe mi-
crophone that records the response is sealed into the ear canal, ex-
ternal sound can often reach the microphone because of the acous-
tic transparency of the ear canal in newborns. Consequently, a cov-
ered isolet or infant sound-attenuating test chamber can improve
the success of infant OAE testing.
An advantage of the use of OAEs for infant hearing screening
is the relative ease and speed of test administration. No electrode
application is required, but a tiny probe must be carefully fit and
sealed into the infant's ear canal. Testing in a cooperative infant
can be completed in a few minutes, but crying and even breathing
noise can dramatically increase the amount of averaging that must
be accomplished to distinguish a small OAE response from the
background noise.
194 Y.S. Sininger

Reviewing results on this topic is complicated by the lack of


consensus on the exact pass-fail criteria to use. A survey of Euro-
41
pean applications of TEOAEs to infant screening found more than
21 different scoring criteria, and the percentage of infants who
could pass such criteria ranged from 6 1 % to 9 0 % . Consequently,
results of sensitivity and specificity of OAE as a screening device
for newborns are mixed. Several studies have found that failure
rates, and consequently false positives, of TEOAE screening proto-
4 2 4 3 4 4 , 4 5
cols are unacceptably h i g h . ' Other s t u d i e s claim much bet-
ter results, but the sensitivity and specificity results must be care-
fully examined. For example, White et al. claim sensitivity of 1 0 0 %
and specificity of 8 2 % using TEOAEs in a mixed population of
45
high-risk and normal-nursery infants. However, the infants who
passed initial screening were not followed up for actual hearing
status; rather, White et al. assumed that they were normal. In ad-
dition, a two-stage screening process for the OAEs was used, which
can artificially inflate the positive characteristics of the screening
process. In fact, 2 7 % of the infants failed the initial stage of screen-
ing and had to be reevaluated at 6 weeks.
There also is some confusion over the actual passing criterion.
White et al. state that they have three categories of response: a pass,
a fail, and a partial pass. A pass is an OAE with 3 dB SNR in the
three test bands between 1 and 4 kHz. A partial pass is when a 3 dB
SNR is found in fewer than 3 bands, and a fail is when none of these
frequency bands meet the 3-dB criterion. Infants with partial pass
are referred for rescreen at 6 weeks, but it is not clear how they are
considered relative to pass-fail at the 6-week rescreen. It is also im-
portant to note that a significant number of infants ( 1 8 % of those
scheduled to return) who demonstrated partial passes or fails at ini-
tial test were not seen at 6 weeks due to loss of family contact, bro-
ken appointments, or refusal to participate. The use of a delayed
second-stage screening induces this type of loss to follow-up. Al-
though this problem exists at all stages of screening, it may be exac-
erbated by a high fail rate of a test at initial screening.
Kennedy et al. compared automated and conventional ABR
with TEOAE in a group of newborns from high-risk and normal
44
nurseries. They found that the initial failure rate using a
moderate-level click for OAE was around 5 % , but this excluded the
infants with craniofacial anomalies and family history, on which
more than 2 0 % of the infants failed. All infants were extensively
followed up in the British study. Ten infants in this study were
found to be hearing impaired and three of those had passed the neo-
natal screening. These three, however, were infants with persistent
Screening for Hearing Loss in Neonates 195

otitis media. Because this condition may not have been present at
birth, it is unclear if these constitute a false negative on the new-
born screening. This issue will need to be addressed in all studies
in which a follow-up behavioral test of hearing, say at 6 months or
later, is used as a gold standard to validate the newborn test.
The most current findings with TEOAE show that it is very im-
portant to clear the ear canal of debris before testing and to ma-
nipulate the ear canal to ensure against occlusion. When this is
done, and when evaluations are delayed until more than 24 hours
after birth, a much more acceptable pass rate (> 9 0 % ) can be ob-
tained for TEOAE universal newborn screening.

The ABR occurs during the first 10 to 20 ms after the stimulus and,
as the name implies, is generated in the auditory nerve and brain
46,47
stem auditory p a t h w a y . This evoked potential is present as
4
early as 25 weeks' gestational age and can be reliably recorded
regardless of sleep state. Consequently, the ABR is the most com-
monly used measure of auditory function, especially hearing sen-
sitivity, in newborns and young children.
Unlike the OAE, which does not depend on neural input, the
ABR is a representation of the neural impulses generated in the co-
chlea and transmitted via the auditory nerve to the brain stem. For
that reason, the ABR is sensitive to cochlear damage and sensory
hearing loss but will also be affected by neural disorders. This can
be both a strength and a weakness of this technique.
The ABR is generally divided into two categories for the pur-
poses of newborn screening. The ABR is referred to as "automated"
or conventional ABR. The test procedure is similar for both; how-
ever, the decision regarding the presence or absence of response is
made by computer algorithm in the automated version and by an
examiner via visual inspection of waveforms in the other. (For a
detailed description of automated objective analysis of ABR, see
48
Hyde, Sininger, and D o n . ) The distinction between automated
and standard ABR is an important one for several reasons. Auto-
mated detection should give fairly consistent results that reflect the
character of the population tested, whereas subjective detection
may show large variability across studies due to differences in judg-
ments across examiners. Automated detection also takes advantage
of optimizing the number of averages or sweeps needed to reach
an acceptable response in a given infant, rather than assuming that
a fixed number of sweeps is necessary, as is common with conven-
196 Y.S. Sininger

tional ABR. Consequently, although automated ABR may take more


time on difficult infants or those that will ultimately fail the test,
it will require much less test time on average to test an infant who
is normal. Because the majority of newborns will be normal and
44
pass, the automated ABR will take less time per infant.
The most widely used brand of automated ABR is the ALGO,
of which there are several models. It should be noted that although
some use automated ABR and ALGO synonymously, there are in
fact many manufacturers and types of automated ABR. The NIH-
funded project, for example, used a detection algorithm known as
4 9
F s p , which estimates the SNR in the ABR. This technique has
4 4 , 50
also been applied to detection with T E O A E s .
One recent criticism of ABR for screening has been cost. In fact,
there are manufacturer-specific costs, related to disposable sup-
plies that are not inherent to ABR testing. Cost and time for prepa-
ration and electrode application, however, must be considered
when evaluating test time for ABR. However, the averaging pro-
cess itself, once an infant is calmed, can take less than a few min-
utes to perform.
One study of ABR for infant screening stands out because of
the completeness of the data. The United States' health care sys-
tem makes long-term follow-up for validation of early screening
very difficult, because after infants leave the hospital, if they re-
ceive pediatric care, they do so at a variety of settings. However,
in the Canadian health care system, pediatric follow-up is more
51
consistent. Hyde et a l . were able to evaluate at-risk infants using
an ABR with a series of stimulus levels, between 3 and 12 months
of age when the auditory response was felt to be stable. These au-
thors then compared the initial ABR results of 713 infants (1,367
ears) with pure-tone audiometry obtained at 3 to 8 years of age.
The nature of this data allowed them to vary the target disease by
level and by type, as well as to choose among stimulus levels used
during screening and compute the sensitivity and specificity in
these various conditions. The best performance came when the
ABR was used to predict sensorineural loss alone. Using a 40-dB
screening stimulus and a 40-dB + target hearing loss level, the sen-
sitivity of the test was 0.98 and the specificity was 0.96. With a
30-dB screening level, the sensitivity rises to 1.0 and specificity
falls slightly to 0 . 9 1 .
51
Hyde et al. used conventional ABR testing with the infants.
Herrmann et al. have summarized results comparing the ALGO-I
to conventional A B R and found that sensitivity ranged from 80%
5 2
to 1 0 0 % and specificity from 9 6 % to 9 8 % . In other words, in
Screening for Hearing Loss in Neonates 197

terms of pass/fail performance, it is reasonable to expect an auto-


mated detection algorithm-based A B R screening device will work
as well as a conventional screener. Automated ABR has been in
place in many large-scale NHS programs and has been shown to
be fast and accurate. Finitzo has screened more than 3,000 infants
in Texas, using automated ABR, and has a pass rate of 9 4 . 7 % at
one hospital and 9 8 . 6 % at another (personal communication). Sta-
tistics from the state of Colorado in 1 9 9 6 , using an automated ABR
screening 50,627 infants, had a pass rate of 9 3 % (Vickie Thomp-
son, personal communication).

COMBINED ABR-OAE PROTOCOLS


The NIH Consensus Statement recommends that the two screen-
ing devices be combined in a two-stage screening that takes advan-
tage of the strengths and downplays the weaknesses of each. Ac-
cording to the statement, the ABR seems to take more time than
the OAE but has better specificity. Consequently, the faster OAE
test should be used as a first-stage screening allowing many infants
to be quickly passed. By this logic, infants who pass stage one
would require no further follow-up. Because the OAE tends to fail
many more infants than truly have hearing loss, a second stage of
screening using the more specific ABR would immediately follow
for all infants who fail the OAE. Thus, the "more expensive" and
"slower" ABR test will be used for only a small subset of the origi-
nal group, cutting down on cost but increasing specificity.
Very little data exist now on the actual performance of such a
two-stage protocol. When it has been applied, the performance
characteristics of the screening have improved. Many of the
assumptions on which the two-stage screening was based have
been challenged. It remains to be seen how these combined proce-
dures will work in practice, but in theory and in the laboratory, a
combined test approach seems reasonable. However, as more in-
formation becomes available, recommended protocols will and
should change.

AUDITORY NEUROPATHY
Screening for auditory disorders has assumed that the nature of the
hearing loss to be detected was either sensory (cochlear hair cell)
or conductive in nature. In that case, we would expect similar but
not exact results from ABR and OAE. However, as the OAE and
ABR techniques have been more readily applied and refined, so
has the ability to distinguish cochlear and neural function. A sig-
198 Y.S. Sininger

nificant group of patients has been identified in whom cochlear


function appears normal, yet function of the primary auditory
53-55
nerve is severely c o m p r o m i s e d . These children have no ABR
with any stimulus and clearly present often robust OAEs. Children
with this disorder are found to have hearing loss, significant diffi-
culty with speech perception, and appear to receive very little help
from conventional intervention such as hearing aids. It is reason-
able to expect that children with auditory neuropathy will be found
primarily in the NICU. Stein, et al have found a significant increase
in infants with this disorder among those with hyperbilirubinemia
55
who require exchange transfusion. It remains to be seen what the
incidence of this disorder may be. However, the two-stage proto-
col that calls for first-stage OAE would certainly pass and miss
these children. As we learn more about the incidence of this dis-
order, we can make better predictions on the need for modifica-
tion of infant screening protocols.

PERSONNEL AND COST ISSUES


The level of training needed to carry out universal NHS will be an
important factor in the cost and acceptance of such programs. The
NIDCD multicenter study used personnel with a wide range of ex-
pertise to carry out the screening, and those data will cast light on
the consequences of training on the actual execution of the test-
ing. However, both ABR and OAE are well suited to automation
and consequently to being performed by trained technicians. All
levels of expertise will be needed in some capacity for a well-
executed universal NHS program. However, program costs will be
contained best if the expertise of each professional is used at the
appropriate level. Cost estimates for universal hearing screening
programs vary greatly. However, current estimates range from about
$15 to $35 per infant screened, with $25 as a reasonable estimate
assuming technicians are used as screeners.

PARENTAL CONCERNS
Among the arguments against NHS is the feeling that early identi-
fication of hearing loss may destroy the bond between infant and
parent. Other than concern, no real evidence of this happening
has been published. In my experience, parents bond as well with
their children with hearing loss as they do with children who have
normal hearing sensitivity, but in many instances, they are frus-
trated by the breakdown in communication. Dramatic advances in
language abilities of early-identified children with hearing loss
Screening for Hearing Loss in Neonates 199

should, in fact, lead to closer communication between these infants


and their parents than was possible before early identification.
When questioned specifically, a majority of parents of children
with hearing loss said they were dissatisfied with the age at which
their child's hearing loss was identified and that they would have
56
welcomed an early identification program.
Another advantage of early identification for parents and fami-
lies is the possibility of early genetic counseling. More than 5 0 %
57
of congenital hearing loss is due to genetic c a u s e s . Parents have
the right to know, for family planning, what the chances are for
recurrence of hearing loss among siblings, as well as any impor-
tant complications that may arise, such as progressive blindness
due to retinitis pigmentosa in the case of Usher's syndrome, in their
children with hearing loss.

CURRENT STATUS OF NEWBORN SCREENING IN THE UNITED


STATES
At the time of this writing, six states have legislated universal NHS
programs. These include Hawaii, Rhode Island, Mississippi, Colo-
rado, Louisiana, and Connecticut. Several other states, including
Pennsylvania and California have legislation that is pending. Sev-
enteen other states have some form of recommended or mandated
NHS based on a high-risk register. In addition, the New York De-
partment of Health funded a pilot project in 1995 that evaluated
universal NHS in seven hospitals.
There is also significant activity related to NHS on the part of
the Federal government. The department of Maternal and Child
Health has funded Dr. Yoshinaga-Itano and colleagues in Colorado
to provide guidance and technical support to other states on the
implementation of NHS programs. The Center for Disease Control
sponsors a monthly national conference call to discuss issues sur-
rounding universal newborn screening. On November 1 1 , 1997,
Representative James Walsh from New York introduced a bill, H.R.
2 9 2 3 , "Early Hearing Loss Detection Diagnosis and Intervention
Act of 1 9 9 7 , " that will provide funding for development of state-
wide early detection and intervention networks, provide technical
assistance, and promote further research on NHS. Finally, it is ex-
pected that among national health care objectives, Secretary of
Health and Human Services Donna Shalala will specifically
include an initiative for universal newborn hearing screening.
Although many questions are left unanswered, much progress
has been made toward adoption of universal newborn screening
200 Y.S. Sininger

for hearing loss. It remains for individual states to adopt legisla-


tion that makes identification of significant hearing impairment
during the newborn period a standard of practice. Perhaps no other
event or technical advancement will do more to improve the out-
come of the communication ability of children with hearing loss.

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CHAPTER 11
Management of the
Abnormally Patulous
Eustachian Tube
Charles D. Bluestone, M.D.
Eberly Professor of Pediatric Otolaryngology, University of Pittsburgh
School of Medicine; Director, Department of Pediatric Otolaryngology,
Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania

S election of the safest and most effective management options


for patients who have a patulous eustachian tube depends
upon many factors. Some individuals have a patulous tube and
rarely, if ever, have complaints referable to this condition. Others
have an abnormally patulous tube that is associated with debili-
tating symptoms that may, when bilateral, even lead to distur-
bance of speech or cause significant psychologic impairment. At
rest, the normal eustachian tube is closed. It actively opens
during swallowing but is considered patulous if it is open at rest.
During periods when the tube is patulous, there are air flow and
sound pressures from the nasopharynx to the middle ear, and the
patient may experience autophony, that is, the awareness of
1
hearing one's own v o i c e . Autophony may also be described as
a roaring sound in the ear synchronous with respiration, fluctu-
ating fullness and "blockage" in the ear, a feeling of talking into
a barrel, or such loud perception of one's voice that normal
2 3
conversation is i m p o s s i b l e . '
The first description of the patulous eustachian tube was by
Schwartze in 1864 when he reported the presence of a scarred atro-
4
phic eardrum moving synchronously with respiration. In 1867,
5
Jago reported having this affliction himself. Zollner and Sham-
baugh noted that patients with abnormally patulous eustachian
6 7
tubes complained of autophony. ' Despite more than a century
having passed since these early reports, management of this disor-
der has remained a difficult problem.
Advances in Otolaryngology-Head and Neck Surgery, vol. 12 nnrz
® 1 9 9 8 , Mosby, Inc. 205
206 CD. Bluestone

Before describing the nonsurgical and surgical methods of


management that are currently available, I will review the epide-
miology of the patulous tube condition, the physiology and patho-
physiology of the eustachian tube, and the etiology, clinical pre-
sentation, and methods of diagnosis of the patulous tube that are
currently available in the clinician's office.

EPIDEMIOLOGY
The patulous eustachian tube is a common occurrence inasmuch
as the tube has been found to be patulous in otherwise normal in-
dividuals. This condition has been identified in a small percent-
age of asymptomatic subjects when eustachian tube function is
tested. Zollner cited an incidence of 0 . 3 % in the general popula-
6
tion. Munker diagnosed a patulous eustachian tube in 6 . 6 % of 100
6
women who had a normal otoscopic examination. Elner and col-
leagues assessed eustachian tube function in a group of 102 adults
who had a negative history for middle ear disease and a normal
9
otologic examination, in a pressure chamber in Malmo, Sweden.
Of these 102 subjects, four ( 4 % ) were found to have patulous eu-
stachian tubes. It is likely that a small number of individuals who
have no symptoms of a patulous tube have a tube that is closed at
rest but its response to applied positive and negative pressure re-
veals a patulous tube; probably the tube is semipatulous.
Although the abnormally patulous eustachian tube that is
symptomatic is relatively uncommon, it is not rare. At the Mayo
Clinic, the diagnosis was made in 41 patients between 1940 and
1959 and in 95 patients during the 7-year period from 1960 to
1 0
1 9 6 6 . Chen and Luxford reported that 46 patients at the Oto-
logic Medical Group in Los Angeles had the diagnosis of a
1 1
symptomatic patulous eustachian tube from 1974 to 1 9 8 1 .
Pregnancy may be associated with symptoms of eustachian
tube dysfunction in which the tube may either be obstructed or pa-
tulous. The definitive study of this problem was conducted by
12
Derkay. He assessed eustachian tube function using the nine-step
tympanometric test and sonotubometry in three groups of women:
(1) 20 pregnant volunteers who had symptoms of eustachian tube
dysfunction; (2) 20 asymptomatic trimester-matched pregnant sub-
jects; and (3) 20 aged-matched women with no otologic symptoms
who acted as controls. Of the 20 symptomatic women, 16 (80%)
had eustachian tube dysfunction, whereas only nine ( 4 5 % ) of the
asymptomatic pregnant subjects and six ( 3 0 % ) of the control sub-
jects had dysfunction, a significant difference. Of these 60 women,
Abnormally Patulous Eustachian Tube 207

seven had a diagnosis of a patulous eustachian tube: of the 20 con-


trol subjects, one ( 5 % ) had a patulous tube, and three women in
each of the two groups of pregnant women also had patulous tubes.
When the three symptomatic pregnant subjects were retested in the
postpartum period, all three were asymptomatic and no longer had
patulous tubes. The conclusion from this study is that symptoms
related to the patulous tube condition associated with pregnancy
are relieved after childbirth.
As early as 1 8 7 3 , Rumbolt, and later Bull, commented that the
13,14
diagnosis requires constant awareness and clinical v i g i l a n c e .
Heightened awareness is an important component to the increased
frequency of the diagnosis.

PHYSIOLOGY AND PATHOPHYSIOLOGY OF THE EUSTACHIAN TUBE


The eustachian tube is part of a system of contiguous organs includ-
ing the nose, pharynx, middle ear, and mastoid gas cells (Fig 1).
The eustachian tube is not just a tube; it is an organ consisting of
a lumen with its mucosa, cartilage, surrounding soft tissue,
peritubal muscles (i.e., tensor veli palatini, levator veli palatini,

FIGURE 1.
T h e eustachian tube is part of a system that includes the palate, nose, and
nasopharynx at its proximal end and the middle ear and mastoid gas cells
at its distal end.
208 CD. Bluestone

salpingopharyngeus, and tensor tympani), and its superior bony


15
support, the sphenoid s u l c u s . The structure of the tube is
closely associated with function. The eustachian tube has at least
three physiologic functions with respect to the middle ear: (1)
pressure regulation (i.e., ventilatory function) of the middle ear to
equilibrate gas pressure in the middle ear with atmospheric
pressure; (2) protection from nasopharyngeal sound pressure and
secretions; and (3) clearance (and drainage) of secretions pro-
duced within the middle ear into the nasopharynx (Fig 2). A basic
understanding of the physiologic function of pressure regulation
and the protective function will be helpful in comprehending the
patulous eustachian tube.

PRESSURE REGULATION ("VENTILATORY FUNCTION")


Regulation of pressure within the middle ear is the most impor-
tant function of the eustachian tube. Hearing is optimum when the
middle ear gas pressure is relatively the same as the air pressure
in the external auditory canal, that is, tympanic membrane and
middle ear compliance is physiologic. In normal tubal function, in-
termittent active opening of the eustachian tube, due only to con-
1e 19
traction of the tensor veli palatini muscle during swallowing, ~
maintains nearly ambient pressures in the middle ear (Fig 3). Open-
ing of the eustachian tube permits gas exchange and equalization
of pressures between the environment and the middle ear. Under
physiologic conditions, the fluctuations in ambient pressure are bi-
directional (either to or from the middle ear), relatively small in
20
magnitude, and not readily appreciated. These fluctuations
reflect the rise and fall in barometric pressures associated with
changing weather conditions and elevation, or both.

PROTECTIVE FUNCTION
The eustachian tube normally protects the middle ear from
unwanted sound pressure (breathing and speech-produced) and
foreign substances (secretions) from the nasopharynx when the
tube is physiologically closed, and from nasopharyngeal secretions
during active opening due to its anatomical structure, which also
depends on an intact middle ear and mastoid so that a middle ear
and mastoid gas cushion is present. In the healthy individual, dur-
ing swallowing activity the nasopharynx is separated from the me-
sopharynx and hypopharynx and oral cavity due to velopharyn-
geal closure. Thus the nasopharynx—and eustachian tube-middle
ear—is protected from normal (saliva and food) and abnormal ma-
Abnormally Patulous Eustachian Tube 209

Pressure Regulation

Protection
Mucociliary
activity

Clearance
FIGURE 2.
Three physiologic functions of the eustachian tube (ET) related to middle
ear (ME). Abbreviations: NP, nasopharynx; TVP, tensor veli palatini
muscle; TM, tympanic membrane; Mast, mastoid gas cells; EC, external au-
ditory canal.
210 CD. Bluestone

FIGURE 3.
Physiologic active opening of the eustachian tube (ET) during swallowing
activity at which time the tensor veli palatini muscle (TVP) contracts and
dilates the tubal lumen. Abbreviations: NP, nasopharynx; ME, middle ear;
Mast, mastoid gas cells; EC, external auditory canal.

terial. Also, during swallowing there is cessation of breathing and


speech.
The anatomy of the tubal lumen favors protection. The lumen
is shaped like two cones joined at their apices. The juncture of
the cones is the narrowest point of the lumen and has been called
the isthmus, and its position is usually described as at or near
the juncture of the osseous and cartilaginous portions of the tube.
The lumen at this point is approximately two mm high and one
21
mm w i d e . From the isthmus, the lumen expands to approxi-
mately 8 mm to 10 mm in height and 1 to 2 mm in diameter at
22
the pharyngeal orifice. The isthmus portion of the tube most
likely aids in protection of unwanted secretions from the naso-
pharynx entering the middle ear. This anatomical structure has
Abnormally Patulous Eustachian Tube 211

b e e n l i k e n e d t o a flask w i t h a n a r r o w n e c k , i n w h i c h l i q u i d i n t h e
n e c k (or t h e l u m e n o f t h e e u s t a c h i a n t u b e ) i s i m p e d e d from
e n t e r i n g t h e b u l b o u s p o r t i o n o f t h e flask (or t h e m i d d l e ear-
m a s t o i d gas c e l l s ) d u e t o t h e r e l a t i v e p o s i t i v e p r e s s u r e ( t h e m i d d l e
2 3
e a r "gas c u s h i o n " ) t h a t d e v e l o p s i n t h e b o d y o f t h e f l a s k .

PATULOUS EUSTACHIAN TUBE


W h e n the e u s t a c h i a n tube is patulous, there is a failure of passive
closing. T h e pressure regulatory function is not only unaffected, it
is e n h a n c e d , b e c a u s e the m i d d l e ear is open to the n a s o p h a r y n x
even during rest (Fig 4 ) . However, protective function is impaired

FIGURE 4.
Ventilatory function in the normal and patulous eustachian tube (ET). In
the normal condition, the tube is closed at rest (A) and actively opens,
due to contraction of tensor veli palatini muscle (TVP) during swallow-
ing, which allows pressure regulation (i.e., ventilation) of gas between na-
sopharynx (NP) and middle ear (ME) (B). When the tube is patulous, the
ET lumen is open at rest (C), as well as during active opening (D). Abbre-
viations: TM, tympanic membrane; Mast, mastoid gas cells; EC, external
auditory canal.
212 CD. Bluestone

in the patulous condition. Sound pressures, such as those pro-


duced by breathing and speech, developed in the nasopharynx
are transmitted to the middle ear, because the tube is open at rest
(Fig 5). However, the middle ear can still be protected from naso-
pharyngeal secretions due to the anatomy of the tubal lumen and
the middle ear gas cushion. On the other hand, certain special
populations that have a high incidence of middle ear infection,
24
such as Native A m e r i c a n s , and patients who have Down syn-
25
d r o m e , have been identified as having abnormally patent eusta-
chian tubes, that is, either patulous or semipatulous, which is most
likely causally associated with their rate of middle ear infection. It
is also important to note that the tube may not be patulous at all
times, nor totally hyperpatent—the tube may be semipatulous—at
all times, which may explain the reported success of tympanos-
tomy tube insertion in some patients (see below).

Sound p r e s s u r e

C e s s a t i o n of C e s s a t i o n of
breathing & s p e e c h breathing & speech

N O R M A L EUSTACHIAN T U B E PROTECTIVE PATULOUS EUSTACHIAN T U B E


F U N C T I O N FOR S O U N D P R E S S U R E

FIGURE 5.
Effect of nasopharyngeal (NP) sound pressure on the middle ear (ME) in
the normal and patulous eustachian tube (ET). In the normal ear, the ET
is closed at rest, which protects the ME from sound pressures produced
in the NP by breathing and speech (i.e., protective function of ET) (A).
During swallowing—and active opening of the tube—breathing and pho-
nation ceases (B). When the tube is patulous, NP sound pressures are trans-
mitted to the ME, inasmuch as the ET is open at rest (C), but sound pres-
sures are not transmitted during swallowing (D). Abbreviations: TVP, ten-
sor veli palatini muscle; Mast, mastoid gas cells; EC, external auditory
canal.
Abnormally Patulous Eustachian Tube 213

The patulous eustachian tube can be included in the spectrum


of conditions termed "closing failure of the eustachian tube,"
which has been identified in normal individuals, but also associ-
ated with middle ear effusion, atelectasis, retraction pockets, and
26
cholesteatoma.

ETIOLOGY AND PATHOGENESIS


In most cases, the etiology of the patulous tube remains obscure;
however, there are known causes of this condition. Weight loss is
1 0 , 2 7
one of the most common known c a u s e s . Atrophy and scarring
of the nasopharyngeal muscles secondary to a cerebral vascular ac-
cident, poliomyelitis, multiple sclerosis, radiotherapy, and iatro-
genic and traumatic injuries to the fifth cranial nerve may result in
7 , 2 8 - 3 0
a functionally patulous eustachian t u b e . Muscular dysfunc-
tion secondary to direct damage to the tensor veli palatini muscle
during cleft palate surgery, combined with postoperative nasopha-
1
ryngeal adhesions and fibrosis, may cause a patulous tube. Sham-
baugh and Pulec proposed that repeated tonsil and pharyngeal in-
fections can alter pharyngeal function to the point of causing a pa-
7 , 3 1
tulous eustachian t u b e . Palatal myoclonus has also been
3 2 , 33
associated with a patulous eustachian t u b e . Using endoscopy,
Yamaguchi and associates have described the pharyngeal orifice of
the patulous tube in some patients as being atrophic, having en-
larged fossa of Rosenmuller, and having the floor of the pharyn-
34
geal orifice that fails to elevate during swallowing.
Increase in compliance of the eustachian tube has been
reported to be an important factor in the pathogenesis of eustachian
tube dysfunction and the pathogenesis of middle ear disease in cer-
3 5 , 36
tain high-risk populations, such as infants and young c h i l d r e n .
However, Sakakihara and associates assessed eustachian tube com-
pliance and ventilatory function in 14 teenagers and adults with
37
patulous eustachian t u b e s . These authors reported that the patu-
lous eustachian tubes had decreased compliance, or increased stiff-
ness, compared to a group of 19 normal control subjects.
Pregnancy (as described above) and supplemental estrogen are
2 9 , 3 1 , 3 8 , 39
implicated in the etiology of a patulous eustachian t u b e .
High levels of estrogen may lead to thinning of intraluminal eusta-
chian tube secretions or an increase in relaxin, a hormone known
40
to increase ligamentous relaxation in the p e l v i s . Estrogen also af-
fects prostaglandin E levels, with a subsequent effect on surfactant
41
l e v e l s . Elevated surfactant levels may decrease the intraluminal
surface tension with the development of a more patulous eusta-
214 CD. Bluestone

chian tube. Less common conditions associated with a patulous eu-


stachian tube are chronic gum chewing, dental malocclusion, con-
tinued voluntary or involuntary subluxation of the temporoman-
dibular joint, and skull dysmorphology such as brachycephaly.

CLINICAL PRESENTATION
It is important to understand that the eustachian tube may be pa-
tulous periodically in normal individuals who are relatively
asymptomatic. Some patients will describe activities, such as vig-
orous exercise, that precipitate the condition, but the associated
symptoms are self limited and not troublesome. It is not uncom-
mon for women to have a short interval of symptoms of a patulous
tube during the menstrual cycle, which rarely comes to the atten-
tion of the clinician. But on the other hand, some patients have a
chronic problem with the condition. T h e most frequent symptom
associated with an abnormally patulous eustachian tube is auto-
phony, which is usually fluctuating and does not become apparent
until the patient has been erect for several minutes. Relief comes
from assuming a supine position or by placing one's head between
42
the k n e e s . These maneuvers effectively increase venous conges-
tion in the peritubal area. Acute rhinitis or any increase in edema
of the nasal mucosa and postnasal space usually is associated with
1
an improvement in symptoms. Symptoms may be exacerbated by
2
topical or systemic decongestants, fatigue, or nervousness.
Patients may present with an apparent psychoneurotic condi-
3 , 4 3
tion. Manipulation of the mandible as a means to close off the
eustachian tube may give the appearance of a tic or manifestation
of neurotic behavior. I have seen one young woman, who had a
long-standing unilateral patulous eustachian tube, turn her head
to the opposite side every 1 to 2 minutes as if she had a tic. In
reality, she was closing her tube with this maneuver, which allevi-
ated her symptoms. This aberration disappeared after successful
management (see "Catheter Obstruction of the Eustachian Tube,"
below).
Hyponasality and hyporhinolalia secondary to the attempt to
close the eustachian tube is a less common presentation of a patu-
1 , 4 4
lous eustachian t u b e . Ringing tinnitus, conductive hearing loss,
and vestibular symptoms are uncommon characteristics of a patu-
lous eustachian tube. Robinson reported an association between
45
patulous eustachian tubes and sensorineural hearing l o s s .
An important aspect of the failure of the tube to adequately
2b
close has been emphasized recently by Falk and Magnusin, who
Abnormally Patulous Eustachian Tube 215

have identified a large number of adults who habitually sniff in an


effort to close the tube. These investigators have found patients
who develop middle ear underpressures as the result of the sniff-
ing, with subsequent effusion or atelectasis of the middle ear.

DIAGNOSTIC TESTS
When a diagnosis of an abnormally patulous eustachian tube is sus-
pected from the clinical presentation, an intensive search for an
etiology is necessary, because a serious underlying disease may be
present. The diagnostic evaluation of the patient suspected of hav-
ing a patulous eustachian tube starts with a comprehensive history.
Symptoms of autophony as previously described are the hallmark
of the patulous eustachian tube. Autophony improves when the pa-
tient is supine or the head is in a dependent position, with the on-
set of symptoms developing within minutes or hours of assuming
42
an upright position. Otoscopy may be normal; however, tympanic
membrane findings may include atrophic changes. Synchronous
movement of the tympanic membrane with respiration has been
4 4 6 4 7
documented by Schwartze, Hartman, and V o l t o l i n i . ' - Oto-
scopy should be performed using a microscope with the patient in
the upright position, because engorgement of the eustachian tube
45
while in the recumbent position relieves the c o n d i t i o n . Move-
ment of the tympanic membrane is enhanced by occlusion of one
nares and closure of the mouth during forced inspiration and ex-
piration, or by using the Toynbee or Valsalva maneuvers. Gentle
pneumatic pressure in the external auditory canal may give the ap-
pearance of a flail tympanic membrane. Rarely, respiration and
speech may be heard with a microphone placed in the external au-
ditory canal. Video documentation of a flail tympanic membrane
can also identify a patulous eustachian tube.

TYMPANOMETRY
If a patulous eustachian tube is suspected and the tympanic mem-
brane is intact, the diagnosis can be confirmed by tympanometry.
The first report of using acoustic impedance in the diagnosis of a
4 8
patulous tube was by Metz in 1 9 5 3 . We have described a tympa-
n o m e t r y patulous eustachian tube test that is conducted with the
49 50
patient in the sitting position. ' One tympanogram is obtained
while the patient holds his or her breath and a second is obtained
while the patient is breathing normally. The fluctuation in the tym-
panometric line should coincide with breathing (Fig 6). The fluc-
tuation can be exaggerated by asking the patient to occlude one nos-
tril with the mouth closed during forced inspiration and expira-
216 CD. Bluestone

Normal Ear

Breath-Holding

Breathing

Forced Respirations

Breath-Holding

Breathing

Forced Respirations

TIME ( s e c o n d s )

FIGURE 6.
Examples of tympanometric patulous eustachian tube test. Upper panel
shows a normal test procedure of an ear of an asymptomatic individual.
Trace is relatively unchanged when breath-holding, during quiet breath-
ing, and even during forced respirations with one nostril closed. No naso-
pharyngeal pressure is transmitted to the middle ear: the eustachian tube
is not patulous. In contrast, the lower panel is a typical outcome when
the eustachian tube is patulous. T h e trace is unchanged during breath-
holding, but when breathing, the trace shows synchronous changes that
are exaggerated during forced respirations.

tion or by the Toynbee test. Others have subsequently described


34 51
their experiences using similar impedance t e s t s . '
When the tympanic membrane and the "nine-step" tympano-
metric test is performed to determine if the patient's eustachian
tube can equilibrate applied positive and negative pressure, neither
pressure will be possible because the tube is patulous. These test
results may lead to the erroneous diagnosis of eustachian tube ob-
Abnormally Patulous Eustachian Tube 217

struction. The patulous eustachian tube tympanometric test is re-


quired to make the diagnosis (Fig 6). Virtanen is a proponent of
sonotubometry in diagnosing the abnormally patulous eustachian
52
tube, but this instrument is not available in most clinical settings.

MANOMETRY
A more precise characterization of a patulous eustachian tube is
possible with determination of the passive eustachian tube open-
ing pressure when the tympanic membrane has a tympanostomy
tube or a perforation present. The patulous eustachian tube and
middle ear will not maintain applied positive middle ear pressure,
or the opening pressure is extremely low, such as 50 to 1 0 0 mm
4 9
H 0 , or there is no opening pressure (Fig 7 ) . In the clinical set-
2

FIGURE 7.
Manometric assessment when the tympanic membrane is not intact (i.e.,
tympanostomy tube or perforation present). When positive pressure is ap-
plied to the middle ear in which the eustachian tube is normal, a normal
opening pressure, such as 3 0 0 mm to 4 0 0 mm H 0 , is present (A). In con-
2

trast, when the eustachian tube is patulous, the middle ear will not main-
tain any positive pressure, that is, no opening pressure (B).
218 CD. Bluestone

ting, this accurate method of assessing eustachian tube function


can be accomplished with the use of the manometry system of the
immittance audiometer, or a simple water manometer.

OTHER TESTS
An audiogram should be obtained as part of the evaluation, as hear-
ing loss is often a part of the constellation of complaints associ-
ated with a patulous eustachian tube. Although some reports de-
scribe a unilateral sensorineural hearing loss of unknown etiology
on the same side as a patulous eustachian tube, no clear associa-
tion has been established between a patulous eustachian tube and
45
sensorineural hearing l o s s . Also, all patients should have an au-
diogram before any nonsurgical or surgical procedure to manage
the disorder.
Because a recent history of a patulous eustachian tube may be
present in patients with a central nervous system etiology such as
multiple sclerosis, a magnetic resonance imaging (MRI) scan of the
brain may be diagnostic, and a computed tomographic (CT) scan
of the base of the skull may be of benefit if a neoplasm of the na-
sopharynx was radiated in the past. Tolley and Phelps reported on
the usefulness of CT scans in diagnosing a patulous tube, with ex-
53
amples that included patients with hemifacial m i c r o s o m i a .

MANAGEMENT
Management of the patulous eustachian tube is related to the se-
verity of the condition and the patient's ability to deal with the
symptoms. However, all patients who have an underlying cause, if
found, should be managed appropriately. When a clear etiology is
not apparent, medical and surgical therapy is instituted, which is
aimed at ultimately decreasing patency of the eustachian tube lu-
men. The severity of symptoms will dictate the urgency with which
treatment is implemented.

NONSURGICAL METHODS
Children and adolescents rarely present with a patulous eustachian
tube. In this population, therapy is usually not indicated as the
symptoms are self-limited. An occasional, otherwise healthy child,
usually early in puberty, will have symptoms of autophony with-
out evidence of middle ear effusion, in whom the diagnosis of a
patulous eustachian tube is made by tympanometry. Autophony in
young school-aged children may not be described as such, but they
complain of vague symptoms that are referable to the ear, such as
Abnormally Patulous Eustachian Tube 219

mild otalgia. An explanation of the condition to the patient (and


parent/caretaker) and reassurance that it is an age-related condi-
tion that improves with time is appropriate management. Minimal
symptoms of a patulous tube that occur in any age group may ini-
tially be managed with reassurance and an explanation of the be-
10
nign nature of the affliction. Weight loss is the most obvious eti-
ology in many patients and most responsive to nonsurgical man-
agement. In these patients, it is usually self-limited, and in those
individuals who comply, is responsive to a return to a more desir-
able weight. As little as 6 pounds of weight loss may lead to suffi-
cient atrophy of soft tissue in the peritubal area to result in a pa-
1 0 , 27
tulous t u b e . Weight gain usually results in resolution of symp-
toms.
Elevated estrogen levels may lead to a patulous condition as
previously described. Pregnant women are assured that completion
of the pregnancy will lead to stabilization of estrogen fluxes and a
29, 31 3 8 39
return to normal eustachian tube function. • ' Before the in-
troduction of low-dose estrogen birth control pills, patients com-
plained more frequently of patulous symptoms. Nonetheless, birth
control pills may still be responsible for abnormal eustachian tube
function.
When an etiology for the patulous eustachian tube condition
is not found, or when the contributing condition cannot be effec-
tively treated, for example, from emaciation due to terminal can-
cer, nonsurgical or surgical therapy is indicated.
Medical therapy intended to decrease eustachian tube patency
may be started as an initial course of therapy for patients with mod-
erate symptoms. Dyer and McElveen reported success in alleviat-
ing symptoms in some patients with oral administration of a satu-
rated solution of potassium iodide (SSKI, 10 drops in a glass of
54
juice, three times a d a y ) . This may be combined with the use of
Premarin nasal spray (25 mg in 30 cc normal saline solution, three
drops three times per day). The combination of potassium iodide
and Premarin drops, with the addition of reserpine chlorothiazide
also has been useful but may be associated with lightheadedness.
If this side effect occurs, the medications are discontinued (writ-
ten communication from D.E. Brackmann, M.D., October 1997).
Medical therapy may be tried for 1 month in patients with moder-
ate symptoms before surgical interventions are recommended. Ex-
perimentally, atropine has been shown to reduce the inflation pres-
55
sure and initial opening pressure of a patulous eustachian t u b e .
Medical therapy may not be a plausible first line of management
220 CD. Bluestone

for patients with grossly abnormal otoscopic examinations and de-


bilitating symptoms, and it is rarely successful in the long term
when the condition is chronic.
Procedures intended to cause irritation and inflammation of the
eustachian tube orifice provide transient relief from patulous symp-
toms. Although not widely used in contemporary practice, several
means of creating eustachian inflammation are available: eusta-
chian tube catheterization and insufflation with a salicylic acid/
56 45,57
boric acid solution in a 1:4 r a t i o ; eustachian tube d i a t h e r m y ;
1, 58
silver nitrate cautery, and the application of nitric acid and phe-
59
n o l . Yamaguchi and colleagues swabbed the eustachian tube lu-
men with a 2% solution of silver protein and Bezold powder with
34
short-term s u c c e s s . No long-term success was noted. In my ex-
perience, these procedures are of uncertain benefit, and when suc-
cessful, must be repeated periodically, because they have limited
long-term efficacy.

SURGICAL METHODS
Surgical therapy is an alternative when less invasive methods of
treatment have failed. Although the middle ear should be ad-
equately ventilated when the eustachian tube is abnormally patu-
lous, myringotomy and tympanostomy tube insertion may be help-
11, 3 1 , 6 0
ful. It is likely that these patients have a tubal dysfunction
in which the tube is semipatulous, that is, the patulous condition
alternates with degrees of tubal obstruction. In my experience, myr-
ingotomy with tube placement is an appropriate first surgical thera-
peutic step for this condition. Chen and Luxford reported that of
the 60 ears of 46 patients with a diagnosis of a patulous tube, 32
ears ( 5 3 % ) were successfully treated with tympanostomy tube in-
11
sertion. Also, a more accurate assessment of eustachian tube
function—using manometry, the eustachian tube has either a very
low opening pressure when positive pressure is applied or the
middle ear will not maintain any positive pressure—can be
obtained when a patent tympanostomy tube is in place, rather than
using tympanometry (or sonotubometry) when the tympanic mem-
brane is intact.
Surgical reconstruction of the eustachian tube orifice has been
proposed as a management option to correct a patulous eustachian
tube. Simonton recommended closure of the eustachian tube ori-
81
fice in which a portion of the cartilage is inserted. This proce-
dure had either been unsuccessful in alleviating the symptoms or
led to complete stenosis of the eustachian tube and refractory
middle ear effusion, and is not advised today. Stroud and col-
Abnormally Patulous Eustachian Tube 221
42 62
leagues, and later Virtanen and P a l v a advocated a surgical pro-
cedure on the soft palate that involved transposition of the tendon
of the tensor veli palatini muscle with or without hamulotomy.
With limited follow-up, this procedure was reported to be success-
ful in approximately 7 0 % of cases; long-term follow-up of patients
treated with this method has not been reported. When we
performed this procedure in the monkey model, the animals did
indeed develop negative middle ear underpressures, or effusion,
63
or both, but these outcomes resolved with t i m e . It is highly un-
likely that this surgical procedure is effective for control of the pa-
tient's symptoms for the long term and is not recommended.
Various methods of blocking the pharyngeal opening of the eu-
stachian tube have been reported. Zollner infiltrated paraffin
around the eustachian tube orifice with transient improvement in
6
patulous symptoms. Ogawara and associates infused an absorb-
able Gelfoam glycerin mixture into the eustachian tube with a high
64
recurrence rate within 1 month of the procedure. O'Connor and
Shea injected polytetrafluoroethylene—Teflon paste—into the eu-
1
stachian tube orifice with transient relief. Pulec succeeded in re-
solving patulous symptoms in 19 of 26 patients with an injection
of Teflon paste at the anterior inferior margin of the pharyngeal eu-
10
stachian tube orifice. In my experience, it is difficult to obtain a
desired result using this procedure, even when the amount of Te-
flon injected is controlled by simultaneous monitoring of eusta-
chian tube function. More importantly today, Teflon injection in
the nasopharynx is contraindicated, because serious complications
1
have been reported, such as cerebral thrombosis and death. Most
likely this complication was the result of injection of the Teflon
directly into a blood vessel, inasmuch as initial aspiration to de-
termine if the needle was in a vessel is not possible with the metal
syringe used for this type of injection.

CATHETER OBSTRUCTION OF THE EUSTACHIAN TUBE


Because I have had limited success with the nonsurgical or other
surgical methods reported in the past, I prefer a surgical procedure
we have previously described for managing the chronically abnor-
65
mal patulous eustachian t u b e . This method involves the insertion
of an indwelling catheter into the protympanic (bony or middle
ear orifice) portion of the eustachian tube. The ultimate surgical
method to correct the eustachian tube that does not prevent un-
wanted nasopharyngeal sound pressures (and secretions) from en-
tering the middle ear is to totally obstruct the middle ear orifice of
the tube. This procedure is traditionally used to prevent trouble-
222 CD. Bluestone

some and difficult-to-control otorrhea after radical mastoidectomy.


I have previously described a surgical procedure that is usually suc-
66
cessful in controlling otorrhea when patients have this problem,
but they invariably have had poor hearing and a poor prognosis
for future reconstruction of the middle ear. (The procedure involves
curettage, packing muscle and bone pate into the bony portion of
the eustachian tube, and covering that area of the middle ear with
fascia.) T h e most appropriate candidates are those patients who
have had a radical mastoidectomy, persistent postoperative otor-
rhea, and anacusis. This method of closure would be the last re-
sort for a typical patient with an abnormally patulous eustachian
tube, because their hearing is usually good, and a permanent tym-
panostomy tube or perforation is necessary to ventilate the ear.
Also, complete surgical closure of the eustachian tube is perma-
nent, and the patulous condition may not be a lifelong problem.
By inserting an indwelling catheter, the eustachian tube obstruc-
tion can be reversed by removing the catheter if, on a rare occa*]
sion, the patient desires it to be removed, or if there are postopera-
tive complications or sequelae.

Anesthetic Considerations and Preparation


T h e surgical procedure may be performed with local anesthesia
supplemented with systemic analgesia or under general anesthe-
sia. The type of anesthetic is based on patient preference. Advan-
tages of local anesthesia include the safety of the anesthetic and a
reduced recovery time. Local anesthetic infiltration is used whether
the procedure is performed under mild intravenous sedation or]
general anesthesia. A standard four-quadrant injection is made at
the bony-cartilaginous junction of the external auditory canal us-
ing a solution of 1% lidocaine and 1 : 1 0 0 , 0 0 0 epinephrine using a
25-gauge needle. A significant blanching of the anterior canal wall
may not be possible because of the thinness of skin in this area.
After injection of the ear canal, the ear is prepped with a
providone-iodine solution. If a tympanostomy tube is present, a
piece of cotton is placed in the external auditory canal to prevent
flow of the solution through the tube. The ear canal is irrigated with
a sterile saline solution before the surgical procedure is begun.
Perioperative antibiotics are not used. Any sign or symptom of
infection in the external auditory canal or middle ear is a contra-
indication to performing surgery until the condition is resolved.
Surgical Procedure
The surgical approach to the anterior middle ear and orifice of
the eustachian tube can be achieved in most cases with a trans-
Abnormally Patulous Eustachian Tube 223

meatal anterior tympanotomy, but if the external auditory canal is


too stenotic, or the anterior canal wall overhang obscures ad-
equate exposure, an endaural incision is an alternate method.
Dyer and McElveen have made a modification of my method of
using an indwelling catheter to obstruct the bony portion of the
54
eustachian t u b e . Their modification involves using a large
anterior myringotomy for access to the middle ear as an alterna-
tive to the anterior tympanomeatal flap approach to the middle
ear. Their modified procedure was reported as being successful in
a small series of patients, but it is not preferred by the author,
because there is limited exposure to the orifice of the eustachian
tube.
An anterior tympanotomy is similar to a posterior tympano-
tomy, but the tympanomeatal flap is created on the anterior canal
wall instead of the posterior wall. Using a Rosen knife or "round
knife," an anterior circumferential incision is made 8 mm from
the annulus extending from 12 o'clock to 6 o'clock (Fig 8). The
initial elevation of the anterior tympanomeatal flap is done with
the aid of a Moon elevator. A 3 Fr suction is positioned behind the
elevator to prevent trauma to the flap. If the patient has a large

FIGURE 8.
Incision for anterior tympanomeatal flap (i.e., anterior tympanotomy) in a
right external auditory canal; if the anterior canal wall obscures adequate
visualization of operative site, a microdrill is used for anterior canalplasty,
or endaural approach is used.
224 CD. Bluestone

anterior bony overhang, it may require drilling with a microdrill


to provide adequate exposure. Once the level of the anterior annu-
lus is reached, a cotton pledget soaked with 1 : 1 , 0 0 0 adrenaline
may be placed between the flap and anterior canal wall to prevent
bleeding before entering the middle ear. The anterior annulus is
dissected out of the sulcus with a Rosen needle or "gently curved
instrument." Once the middle ear is entered, the flap is further el-
evated with an annulus elevator or "gimmick." The flap is elevated
to the malleus (Fig 9 ) .
The eustachian tube orifice is identified with direct vision or
with a piece of No. 90 polyethylene tubing (Fig 1 0 ) . The polyeth-
ylene tubing is helpful in assessing the orientation of the eusta-
chian tube lumen. The eustachian tube catheter is fashioned using
an 18-gauge Medicut angiocath (Argyle Medicut, Sherwood Medi-
cal Industries, St. Louis, MO 6 3 1 0 3 ) . The narrowed end of the cath-
eter is cut to leave a total catheter length of approximately 2 cm
(Fig 1 1 ) . The flared end of the catheter is occluded with bone wax
(Fig 1 2 ) . The narrowed end of the catheter is introduced into the
eustachian tube orifice using an alligator forceps (Fig 1 3 ) . Sufficient
pressure is used to obtain a tight fit.

FIGURE 9.
Anterior tympanomeatal flap elevated and orifice of eustachian tube iden-
tified.
Abnormally Patulous Eustachian Tube 225

FIGURE 10.
Small-bore polyethylene catheter (e.g., No. 90) introduced into orifice of
eustachian tube to determine site, direction, and approximate length of 18-
gauge Medicut angiocath (Argyle Medicut, Sherwood Medical Industries,
St. Louis, Mo. 6 3 1 0 3 ) to be inserted.

FIGURE 11.
Small length of Medicut catheter cut to maintain a portion of flared tip.
226 CD. Bluestone

FIGURE 12.
Bone wax inserted into lumen of catheter.

FIGURE 13.
Narrow end of Medicut catheter inserted into orifice of eustachian tube
until tightly in place; flared end is in middle ear but not touching mal-
leus.
Abnormally Patulous Eustachian Tube 227

Once the catheter is secured, a manometer or tympanometer is


used to assess the degree of occlusion of the eustachian tube. With
the tympanomeatal flap still elevated, a sterile olive tip probe is
inserted into the external auditory canal (Fig 14). Using either a
manometer or tympanometer, the pressure is slowly elevated to 4 0 0
mm to 600 mm of water. Obtaining an opening pressure before in-
serting the Medicut catheter is helpful in assessing if the opening
pressure is significantly higher after the catheter has been inserted.
Ideally, there will be no opening pressure and the middle ear and
the obstructed eustachian tube will hold air pressure to the limit
of the manometer/tympanometer. It should be noted that when the
patient is in the supine position, there will be an opening pres-
sure, albeit lower than normal, before inserting the Medicut cath-
eter, because the eustachian tube is engorged in this position. Any
significant leak of air below this level is considered an inadequate
seal and catheter placement is reassessed. If the Medicut catheter
appears to be in place and there is still a leak of air, bone pate (taken
from the anterior auditory canal) can be placed around the edges
of the catheter (Fig 15). After completing the pressure test, the tym-
panomeatal flap is replaced into its anatomical position. At this

M a n o m e t e r or
Tympanometer

FIGURE 14.
Pressure manometer tests if eustachian tube is obstructed at this stage.
228 CD. Bluestone

FIGURE 15.
If the manometric assessment reveals a persistent low tubal opening pres-
sure, a small portion of tissue, such as fat, fascia, or pate can be inserted
laterally between the catheter and the middle ear end (i.e., bony or pro-
tympanic portion) of the eustachian tube.

point, a radial myringotomy is performed in the anteroinferior


quadrant of the tympanic membrane and a tympanostomy tube in-
serted (Fig 16). The ear canal is filled with an antibiotic ointment
to secure the flap. A cotton ball is then placed in the external me-
atus, serving as the only necessary dressing.

Postoperative Care
The tympanostomy tube should be left in place until it spontane-
ously extrudes. Some patients will not require replacement of the
tympanostomy tube if their middle ear remains aerated and they
are without middle ear symptoms of a patulous tube or middle ear
negative pressure/effusion. Apparently there is sufficient gas pass-
ing from the nasopharynx around the catheter and into the middle
ear, but their eustachian tube is no longer patulous. Presumably,
there is enough gas exchange from the nasopharynx into the middle
ear to effectively ventilate the middle ear. However, if middle ear
negative pressure or effusion develops, then a tympanostomy tube
Abnormally Patulous Eustachian Tube 229

FIGURE 16.
Tympanomeatal flap is replaced and a tympanostomy tube is inserted into
anteroinferior portion of tympanic membrane.

must be reinserted. If there is any postoperative problem with the


catheter, such as otorrhea, it can be removed, but this should be
carried out by elevating the anterior tympanomeatal flap as an op-
erative procedure.
The patient is instructed to limit physical activity for a few
weeks to allow for healing of the tympanomeatal flap. Postopera-
tive antibiotics are not routinely used. Patients are instructed to
keep water out of the ear by inserting cotton in the external audi-
tory meatus, with a small amount of petroleum jelly on the out-
side of the cotton, when they are taking a shower, washing their
hair, or swimming. The head should not be submerged during
swimming during the postoperative period and whenever there is
a tympanostomy tube in place. Ear plugs are not recommended un-
til the patient is seen at the postoperative visit to assure that the
canal incisions are well healed.
Patients should be seen at least twice a year to assess the sta-
tus of their symptoms and that of the tympanostomy tube. If there
is some doubt as to the success of the operative procedure during
the postoperative period, a repeat eustachian tube function test can
be performed. The most accurate assessment can be accomplished
230 CD. Bluestone

when a tympanostomy tube is in place and manometry performed


as described above. A tympanometric test is used when the tym-
panic membrane is intact.

Outcome
Of the 12 patients in whom relatively long-term follow-up (2 to 17
years) has been possible, half have had significant, long-lasting re-
lief of their symptoms and have not had complications related to
the tympanostomy tubes. Two patients have extruded their eusta-
chian tube catheters and tympanostomy tubes with continued re-
lief from their patulous tube symptoms. It is felt that these patients
developed adequate scarring of the eustachian tube lumen to ef-
fectively eliminate the patulous condition. Two patients with cath-
eters in place and extruded tympanostomy tubes with intact tym-
panic membranes have not experienced any episodes of middle ear
effusion. This finding supports the concept that in some patients,
there is gas exchange around the Medicut catheter. Because of the
tympanostomy tube, patients have not complained of aural fullness
after catheter placement. One patient who complained of postop-
erative tinnitus wanted the catheter removed, which was done
without any complication. However, that patient still has symp-
toms of a patulous tube bilaterally and has persistent tinnitus in
the previously operated ear, as well as in the unoperated one.
The success of the operation has improved greatly since the ad-
dition of the intraoperative assessment of eustachian tube function
to determine the degree of occlusion of the eustachian tube by the
catheter. Patients operated on early in this series had variable out-
comes.

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C H A P T E R 12
Contemporary Aspects of
Nasal Reconstruction
Shan Baker, M.D.
Professor and Chief, Section of Facial Plastic and Reconstructive
Surgery, Department of Otolaryngology; Director, Center for Facial
Cosmetic Surgery, University of Michigan Medical Center, Ann Arbor,
Michigan

S kin cancer is the most common form of malignancy in


humans, and the skin of the nose is the most common site of
occurrence. This area is also one of the most difficult to cure. A
review of 2,600 patients with cancer of the skin of the head and
neck revealed that basal cell carcinoma was the predominant
histologic type ( 6 9 % ) . Approximately 1 2 % of the patients had
1
cancer of the skin of the nose. Of the 305 patients with cancer of
the skin of the nose, only 6 4 % of occurrences were confined
strictly to the skin of the nose. The remaining 3 6 % extended
intranasally or into the skin of the cheek or upper lip. Approxi-
mately 4 0 % of all recurrent basal cell carcinomas of the head and
2
neck involve the skin of the nose. This is probably related to the
multiple junctions of embryonic fusion planes located in the
central face. Each plane offers a potential site for tumor extension,
often subclinical extension that may not be appreciated on
examination. Specific examples of this phenomenon include
extension of tumor along the periosteum of the nasal bones and
the perichondrium of nasal cartilages, along the columella and
nasal septum, and the junction of the base of the nose with the
melolabial fold.
Small primary basal cell carcinomas occurring on the skin of
the nose may be treated successfully by a number of methods in-
cluding simple excision, electrodesiccation, and curettage. How-
ever, basal cell carcinoma in the alar facial sulcus, along the nasal
columella, and tumors larger than 2 cm should be resected using
3
complete microscopic-controlled margins (Mohs' surgery). Tu-
mors that have morpheaform or basosquamous histology, that are
Advances in Otolaryngology-Head and Neck Surgery®, vol.12 o o c
® 1 9 9 8 , Mosby, Inc. "5)
236 S. Baker

multicentric in origin, or that have other features of aggressive


4, 5
growth should be treated in a similar manner.
With the rising incidence of cancer of the skin of the nose, a
greater number of these tumors are being managed surgically, as
more physicians are being trained in the techniques of Mohs' sur-
gery. This fact accounts for the increasing number of patients who
require nasal reconstruction. This chapter will outline the histori-
cal approaches to nasal reconstruction and discuss contemporary
methods that have resulted in a significant improvement in form
and function.

HISTORICAL APPROACHES
Previous methods of reconstructing full-thickness nasal defects
started with unlined flaps of the forehead, limited in length by the
hairline. The external contour of the nose and the airway became
distorted by scar contraction on the raw undersurface of the flap.
This led surgeons to provide a lining by folding the distal portion
of the covering flap on itself, thereby creating an internal and ex-
ternal surface with the same flap. Although this eliminated the raw
surfaces, a normal hairline position limited the availability of tis-
sue for infolding unless hair was transferred to the nose. Some sur-
geons attempted to modify the classic midline Indian forehead flap
to gain length and provide more tissue for nasal repair, often re-
sulting in unsatisfactory scarring of the forehead. Other surgeons
attempted to provide nasal lining by seeking sources other than
forehead skin. Residual skin from the nose was turned down as a
hinged flap based on scar tissue at the margin of the defect. Local
cutaneous flaps in the form of melolabial flaps were rolled over to
line the ala and columella. Split-thickness and full-thickness skin
grafts were also used for lining, either in a delayed fashion, plac-
ing them on the raw surface of the flap during a preliminary op-
eration, or placed at the time of the flap transposition. In the
former instance, the prelaminated flap was transferred to the nose
a few weeks later. Similarly, free mucosal or composite septal
mucoperichondrial-cartilage grafts were placed beneath the fore-
head flap and then the compound flap was transferred a few weeks
later. Each of these techniques provided both internal and external
epithelial surfaces for full-thickness nasal defects. However, each
method invariably provided a thick, stiff, and often contracted
mass of tissue with compromised vascularity. These methods of
providing nasal lining distorted the shape of the nose and often
contracted, causing obstruction of the airway.
Contemporary Nasal Reconstruction 237

As surgeons attempted to refine techniques for nasal recon-


struction, it became evident that a skeletal framework was neces-
sary to prevent the surface skin and nasal lining from contracting,
which would cause a restriction of the airways, limiting nasal pro-
jection. A rigid support system is necessary to counteract the con-
traction of scar tissue, thus maintaining the shape and projection of
the nose. However, the lining flaps did not provide adequate vascu-
larity for skeletal grafts to survive when used at the time of the flap
transfer. Insertion of skeletal support was usually delayed until the
covering and lining tissues had been transferred to the nose and
had healed. Skeletal support was then added using bone or carti-
lage placed as cantilevered grafts to elevate the dorsum and tip. Un-
fortunately, scar contraction during the healing process often pre-
vented restoration of the normal contour. These techniques limited
the opportunity to shape the nose because of the contracted scar tis-
sue. As a result, reconstruction of large nasal defects often ended
with a blob of amorphic tissue attached to the midface with a di-
minutive airway and only a slight resemblance to the human nose.
In summary, primary bone and cartilage grafts were not used
routinely during the reconstruction of the nose because the avail-
able lining tissue was not sufficiently vascularized to support such
grafts. In addition, the airway was immediately compromised be-
cause of the inherent thickness of lining flaps. Traditionally, skel-
etal support was provided secondarily after the soft tissue portion
of the reconstruction had healed and contracted. This resulted in
bulky, inadequate, and unaesthetic reconstruction.

CONTEMPORARY APPROACHES
During the last decade, reconstructive rhinoplasty has been raised
to a higher level of sophistication, with enhancement of aesthetic
6 8
results thanks to the contributions of Burget and M e n i c k . " These
surgeons have perfected sophisticated methods of nasal repair.
They emphasize replacing surgically ablated tissue with like tis-
sue. Skin is replaced with skin that matches in color and texture
as closely as possible. Cartilage and bone are replaced and mucosa
is used to replace any loss of the nasal lining. The concept of na-
sal aesthetic units has emerged, with an emphasis on reconstruct-
ing an entire unit, even if only a portion of the unit is missing.
Another important concept that has led to enhancement in the re-
sults of restorative surgery has been the emphasis on the placement
of incisions for local flaps along borders of aesthetic regions or
units to maximize camouflage of scars. Whenever possible, local
238 S. Baker

flaps are designed so that they are not transferred across the bor-
ders of aesthetic regions, particularly if the border has a concave
topography. An example of such a border is the alar facial sulcus,
which represents a concave border between three aesthetic facial
regions: the nose, the cheek, and the upper lip.

FACIAL AESTHETIC REGIONS


The face can be divided into topographic regions, each with its own
characteristic skin color and texture, configuration, contour, and
hair growth. Each has an individual shape created by the underly-
ing facial skeleton. The nose is one of the aesthetic regions of the
face and can be divided into several aesthetic units (Fig 1). Each
unit may be overdeveloped or underdeveloped in the individual
nose, but there is a consistent general configuration of the nose
from person to person. There are nine aesthetic units of the nose
identified by distinctive convex or concave surfaces, including the
lobule, dorsum, paired sidewalls, paired ala, paired soft triangles,
and the columella. The lobule shape is determined by the size and
contour of the lower lateral nasal cartilages and is covered by rela-
tively thick sebaceous skin. Each lower lateral cartilage has a dome

FIGURE 1.
A, topographic aesthetic nasal units; B, topographic aesthetic nasal units.
Contemporary Nasal Reconstruction 239

that causes a point of reflected light. Above the lobule is a supratip


depression that separates the lobule from the dorsum. The skin of
the dorsum tends to be less thick and sebaceous than the lobule,
becoming progressively thinner as it ascends to the rhinion and
thickens again as it approaches the glabella. The nasal bones, to-
gether with the upper lateral cartilages and cartilaginous septum
provide skeletal support for the dorsum. The lateral borders of the
dorsum are defined by ridges that represent the lateral shoulders
of the upper lateral cartilages and the junction of the nasal bones
with the frontal processes of the maxilla. These ridges separate the
dorsum from the sidewalls. Each lateral shoulder reflects a line of
light and shadows that separates the lateral walls from the dorsum.
The nasal sidewalls are most often a combination of convex and
concave elements extending laterally from the dorsum to the junc-
tion of the nose with the cheek. Structurally, the sidewalls are sup-
ported by the lateral extensions of the nasal bones and upper lat-
eral cartilages and the medial extension of the frontal processes of
the maxilla. The skin of the sidewalls is thin and less sebaceous
than that of the dorsum and lobule and is separated from the ala
by the alar nasal crease, which is the deepest contour line of the
nose. This crease is continuous laterally with the alar facial sulcus
and together, they circle the alae, delineating them from the lob-
ule, sidewalls, and cheeks. The alar unit itself is a smooth bulge
reflecting a single spot of light and is covered with thick sebaceous
skin similar in texture and porosity to the lobule. The structural
support of the ala is provided by thick fibrofatty tissue that does
not contain cartilage.
The soft triangles are subunits that fill in the span between the
intermediate and lateral crura of each lower lateral cartilage, mak-
ing up a portion of the nostril margins. These triangles are covered
by thin, nonsebaceous skin and have only a small amount of fi-
brous connective tissue for structural support. They are separated
as distinct units by the shadow of the lobule.
The columella, like the lobule and dorsum, is a nonpaired es-
thetic unit extending from the caudal aspect of the lobule to the
upper lip. It is covered by the thinnest of nasal skin and structur-
ally is supported by the medial crura.
The lining for each of the nine esthetic units of the nose is also
distinctive. Thin non—hair-bearing skin lines the lobule, whereas
the soft triangles and ala are lined by thicker skin, the caudal as-
pect of which is hair-bearing. The columella is backed by the mem-
branous septum, which is skin lined. At the piriform aperture, the
240 S. Baker

lining transitions to mucosa, which lines the dorsum and sidewall


units.
Menick has stressed that the goal of restorative nasal surgery
7
is not simply to fill a defect. Wounds should be altered in size,
configuration, and depth to allow reconstruction of an entire unit.
If more than 5 0 % of the surface area of a unit is lost, resurfacing
the entire unit is preferable. This is accomplished by discarding
the remaining skin of the unit and designing the surface flap so it
will cover the entire unit. This positions the scars in the junction
between units where they will lie in depressions or along ridges,
maximizing scar camouflage. By placing the scars in these junc-
tions, they will blend with the normal contour lines of the nose
and will not distract the viewing eye. Resurfacing the entire unit
also takes advantage of the mild trapdoor scar contraction phenom-
enon, which causes the entire unit to bulge slightly, simulating the
7
normal convexity of the lobule, dorsum, and ala.
The surface area and pattern of each unit should be replaced
in such a way as to exactly duplicate it whenever possible. Because
a fresh wound is always enlarged by retraction of the margins, the
contralateral units should be used for designing covering flaps. If
the contralateral counterpart is missing, or if a unit does not have
a matching pair, a template recreating the ideal unit size for that
specific patient is used. Because the nose is a three-dimensional
structure, each unit must duplicate the normal contour. This is ac-
complished by integrating structural support in each step of the
repair. The structural support must be attached to a stable founda-
tion, such as the bone of the maxilla, to prevent it from collapsing
7
or becoming distorted during the healing process. Within the de-
fect, all reconstructed skeletal structures must completely span the
defect. This should be accomplished before wound healing to pre-
vent distortion from scar contraction during the healing process.
Application of the aesthetic unit principles provides a logical
cognitive approach to nasal reconstruction. Missing tissue must be
replaced with like tissue in a quantity and quality that exactly rep-
licate the pattern, surface area, and contour of the absent unit.

LINING FLAPS
Burget and Menick have studied the vascularity of the septal mu-
cosa and have discovered that the entire ipsilateral septal muco-
perichondrium can be transferred with a narrow pedicle contain-
6
ing the septal branch of the superior labial artery. Likewise, the
entire contralateral mucoperichondrium can be turned laterally as
a dorsally based hinge flap to line the sidewall of the nose based
Contemporary Nasal Reconstruction 241
fi
on the anterior and posterior ethmoid arteries (Fig 2). Burget and
Menick have also shown that if both right and left septal branches
are included in the pedicle, the entire septum can be rotated out
of the nasal passage as a composite flap containing a sandwich of
(l
cartilage between the two mucoperichondrial leaves (Fig 3). Such
flaps, whether they be composite or simple mucoperichondrial
hinge flaps, can be designed to extend from the floor of the nose to
within 1 cm of the junction of the upper lateral cartilage and car-
tilaginous septum. The flaps may extend posteriorly well beyond
the bony-cartilaginous junction of the septum, producing a hinged
0
mucosal flap measuring as much as 3 cm wide and 5 cm long.
These authors have also described a bipedicle flap of vestibular
skin and mucosa based medially on the septum and laterally on
the floor of the nasal vestibule. Such a flap is elevated off the un-
dersurface of the lateral c m s and mobilized inferiorly to reline alar
defects (Fig 4 and Fig 6, C). All of these lining flaps have a reliable
vascularity and are thin, providing natural physiologic material for

FIGURE 2.
A, the septal branch of the superior labial artery can supply a large ipsilateral
mucoperichondrial flap hinged on the caudal septum; B, exposed septal cartilage
is removed, maintaining an adequate dorsal and caudal strut; (Continued.)
242 S. Baker

FIGURE 2.
C, contralateral mucoperichondrial flap hinged on the dorsum can be turned lat-
erally to line the cephalic portion of the sidewall; D, a contralateral mucoperi-
chondrial flap hinged on the dorsum can be turned laterally to line the cephalic
portion of the sidewall; E, the ipsilateral flap is used to line the caudal portion of
nasal sidewall and ala.
Contemporary Nasal Reconstruction 243

FIGURE 3.
A, composite flap based on the dual blood supply of the septal branches of the
superior labial artery. A wedge of cartilage is removed to allow flap to be turned
outward; B, composite flap turned outward; C, bilateral hinged mucoperichon-
drial flaps are turned downward to provide lining for the reconstructed nasal ves-
tibule.
244 S. Baker

FIGURE 4.
A, full-thickness defects of the ala that do not extend cephalically more than 1.5
cm may be lined by a bipedicle vestibular mucosal flap based medially on the
septum and laterally on the floor of the nasal vestibule; B, the donor site for the
bipedicle flap is covered with a thin full-thickness skin graft; C, any remaining
skin of the ala is discarded. Auricular cartilage provides structural support to the
nostril margin.
Contemporary Nasal Reconstruction 245

the interior of the nasal passage. Because these flaps are thin and
supple, they do not distort the external shape of the nose nor do
they compromise the airway. Importantly, these well-vascularized
lining flaps allow the primary placement of cartilage grafts for
framework that, when properly fashioned, prevents excessive scar
contraction and nasal distortion.

FRAMEWORK
The dorsum of the nose is supported by the nasal bones and carti-
laginous septum: the sidewalls by the frontal processes of the max-
illae and upper lateral cartilages, the lobule by the intermediate and
lateral crura of the alar cartilages, the columella by the medial
crura, and the ala and soft triangles by stiff fibrofatty connective
tissue. If missing, the nasal framework of each unit must be com-
pletely replaced. Cartilage grafts can be used to replace the miss-
ing framework of the dorsum, lobule, and sidewalls. Additionally,
a strip of cartilage must be placed along the reconstructed nostril
margin whenever the connective tissue framework is missing. In
instances of alar reconstruction, this usually means placing a car-
tilaginous strip that spans the distance from the alar junction with
the cheek to the region of the soft triangle, even though these areas
do not normally contain cartilage. This is required to support the
nostril rim to prevent upward contraction of the nostril margin dur-
ing wound healing.
The function of the framework is to provide contour and main-
tain a patent airway. Framework grafts must be placed at the time
of initial reconstruction and should consist of grafts that, as nearly
as possible, replicate the exact size, shape, and contour of the miss-
ing framework. When covered by a thin, conforming cutaneous
flap, the contour of the framework is distinctively manifested and
produces a normal-appearing restoration of the missing part. The
framework grafts fix in place the soft tissues used in nasal repair
by virtue of providing a skeletal support of both lining and cover.
Bone and cartilage are the tissue grafting materials available to
the surgeon for replacing the framework of the nose. The frame-
work of the nasal dorsum may be replaced with bone or cartilage.
Cranial bone is the preferred material anchored to the frontal bone
with microplates. Limited inferior dorsal defects are best replaced
with septal or auricular cartilage when available. The dorsal frame-
work prevents cephalic contraction and subsequent shortening of
the nose. It also provides shape and projection to the bridge.
The framework of the sidewall can be replaced with septal
bone and cartilage or cranial bone formed into a trapezoid shape
246 S. Baker

and fixed to the dorsum and maxilla. It supports the middle vault
and prevents collapse. It also serves as a foundation for attaching
the lower framework of the nose, specifically the alar cartilages or
their replacements.
The lobule is shaped by the alar cartilages and the preferred
replacement framework is conchal cartilage grafts. By coincidence,
when turned upside down, the contralateral conchal cymba often
closely resembles the shape of the dome cartilage (intermediate
crura), and the conchal cavum resembles the shape of the lateral
crus. Grafts 5 mm wide from this area can be scored and bent to
replace the entire lower lateral cartilages. These grafts can be
placed bilaterally or unilaterally as needed and are fixed to any re-
sidual stumps of the medial and lateral crura. They support the
dome and recreate the contour of the nasal lobule. Additional pro-
jection and shape of the tip can be accomplished with Peck-type
4 X 9 mm cartilage grafts anchored on top of the reconstructed alar
7
cartilages or the fabrication of shield-shaped tip grafts placed cau-
dal to the cartilages.
Structural support for the columella can be provided by con-
chal cartilage grafts described for the lobule, but placed in such a
way as to span the gap in the medial crus or extend all the way to
the nasal spine if the entire medial c m s is absent. Septal cartilage
grafts are very effective for this purpose as well. Grafts must be
scored and bent so they replicate the diverging angle that naturally
occurs at the junction of the medial and intermediate crura.
An alar batten of septal or conchal cartilage 5 mm wide can be
used for the framework of the ala and soft triangles. The natural
curvature of the conchal cartilage makes this material preferable
to septal cartilage when available. A graft should be placed along
the proposed margin of the missing nostril from the alar base to
the nostril apex (Fig 4, C). It is inserted into a deep tissue pocket
in the alar facial sulcus and is attached medially to the framework
of the dome. Similar to the grafts used for the framework of the
dome, grafts must be thinned, scored, and bent to replicate the
bulging contour of the ala. If the nasal defect extends into the soft
triangle, the batten should extend beneath the diverging angles of
the intermediate and lateral crura to span any gap present (Fig 7,
C). The batten fixes the reconstructed alar rim in position, prevent-
ing upward migration and notching of the rim.
In summary, the surgeon must determine what part of the na-
sal framework is missing and replace it completely. Each replace-
ment part must be carefully shaped, thinned, scored, bent, and
fixed with regard to nasal projection, contour, alar rim position, and
Contemporary Nasal Reconstruction 247

symmetry so that it exactly replicates the contralateral counterpart


or the ideal if both components of the framework are missing. The
more able the surgeon is at achieving this goal, the better the aes-
thetic and functional results.

COVERING FLAPS
Small defects of the nasal skin 2 cm or less can sometimes be re-
paired with local flaps harvested from the remaining nasal skin, if
there is sufficient redundancy of skin. Most notable of the local
9
flaps is the bilobe flap as modified by Zitelli. The bilobe flap was
originally designed for repair of nasal tip defects. Each lobe and
the defect were separated by 90 degrees for a total transposition
over a 180-degree arc. Although this recruited tissue for repair at
some distance from the defect, it also maximized the standing cu-
taneous deformities and the likelihood of development of a trap-
door deformity or pincushioning of both the primary and second-
ary flaps. Zitelli has emphasized the use of narrow angles of trans-
fer, such as 45-degree angles between lobes, so that the total arc of
tissue transferred occurs over no more than 90 to 100 degrees.
9
(Fig 5 ) . This reduces the standing cutaneous deformity and pin-
cushioning effects. Bilobe flaps are double transposition flaps that
transfer the wound closure tension from the initial defect through

FIGURE 5.
Bilobe flap designed so that each lobe has a linear axis 45 degrees from
the other. Each lobe is designed around one arc through the center of the
defect and another through the peripheral border of the defect.
248 S. Baker

a 90-degree arc to the donor site areas. A major disadvantage of this


flap is the extensive amount of linear scar that is created on the nasal
dorsum. An alternative design using rhombic-shaped lobes can be
used. With this modification, however, resulting scars do not fall
along nasal topographic borders, and postoperative dermabrasion is
very helpful in obscuring the scars. The bilobe flap is the most com-
monly used local flap harvested within the confines of the nose it-
self. It is best limited to repairing defects of the skin of the lower
third of the nose. It is not well suited for repair of defects of the up-
per dorsum, because the donor site for the secondary flap, by ne-
cessity, lies in the area of the medial canthus where the skin is im-
mobile, making wound closure difficult.
Skin adjacent to the defect is used as the primary lobe of a bi-
lobe flap, thus allowing for an excellent color and skin texture
match. The flap is designed as nearly as large as the defect so little
wound closure tension is exerted on the primary flap. The donor
site for the secondary flap is closed primarily because the second-
ary flap is recruited from the lax skin of the upper dorsum and na-
sal sidewalk The base of the bilobe flap is usually positioned lat-
erally, and the transverse nasalis muscle is included in the sub-
stance of the flap to enhance vascularity.
The bilobe flap is ideal for a small nasal defect (less than 1.5 cm)
located on the nasal tip or sidewall and at least 5 mm from the
margin of the nostril. Preferably the flap is based laterally and is
designed so that the standing cutaneous deformity resulting from
pivoting the flap is removed parallel to, or in, the alar nasal crease
with its apex pointing laterally. The base of the standing deformity
is positioned at the lateral border of the defect, and its base is ap-
proximately one half to two thirds of the diameter of the defect.
The apex of the cone-shaped excision serves as the pivot point for
the flap. Each donor lobe is designed around one arc through the
center of the defect and another through the peripheral border of
the defect (Fig 5). Each flap's linear axis is positioned at approxi-
mately 45 degrees from each other. The primary lobe is positioned
45 degrees from the axis of the defect. The flap is elevated just
above the perichondrium and periosteum of the underlying nasal
framework. If the primary lobe is transferred into a recipient area
with thin skin, the distal flap may require thinning to the level of
the dermis to match the thickness of the skin at the recipient site.
After elevation of the flap, wide undermining of essentially all of
the remaining skin of the nose is important to reduce wound clo-
sure tension, facilitate flap transfer, and minimize trapdoor defor-
mity. The primary lobe of the flap is transposed into the defect and
Contemporary Nasal Reconstruction 249

secured with sutures, and the donor site of the secondary flap is
closed primarily. Lastly, the secondary lobe is transposed and
trimmed appropriately to fit without redundancy the donor defect
of the primary lobe.
The bilobe flap is most useful in patients with thin nasal skin
and laxity of skin along the nasal sidewall. The surgeon can esti-
mate the laxity by pinching the lateral nasal skin between the
thumb and index finger. Patients with thick sebaceous skin have a
higher risk of flap necrosis and development of trapdoor deformity.
Dermabrasion, 6 weeks after flap transfer, is recommended for most
patients reconstructed with a bilobe flap.
Although local nasal flaps can be used to repair defects 2 cm
or less on the nose, the majority of surface defects are best repaired
with skin from the forehead or cheek.

MELOLABIAL INTERPOLATION FLAP


The ala is best resurfaced with cheek skin in the area of the melo-
labial fold. The porous and sebaceous skin of the fold closely re-
sembles the skin of the ala. Menick has noted that as melolabial
flaps contract they become rounded, resembling the contour of the
7
normal ala. Skin of the melolabial fold is limited. Its use can flat-
ten the fold, causing marked asymmetry of the face, and it cannot
be transferred easily to the nasal lobule or dorsum. Skin from this
fold should be transferred to the ala as an interpolated flap, the
pedicle of which crosses over, but not through, the alar facial sul-
cus. The pedicle is superiorly based and may consist of skin and
subcutaneous fat or subcutaneous fat only and is detached from
the cheek 3 weeks after the initial transfer to the nose. Although 3
weeks is a lengthy period for the patient to endure the deformity
caused by the flap, this interval allows the surgeon to aggressively
defat and sculpture the distal flap, both at the time of the flap trans-
fer and at the time of pedicle detachment and flap inset.
For resurfacing the ala, the remaining skin of the ala is removed
and a template is fashioned to represent exactly the shape and sur-
face area of the ala. The contralateral ala can be used for the tem-
plate when present. The template is used to design a flap that is
positioned so that the center of the flap is on a horizontal plane
with the lateral commissure of the lip. The medial border of the
flap should lie in the melolabial sulcus. The flap is designed as an
interpolation flap in which the donor site scar will lie exactly in
the melolabial sulcus (Fig 6). The flap is based on perforating ves-
sels from the facial artery that penetrate just superior and inferior
to the zygomatic major muscle. Incorporating these perforators
250 S. Baker

FIGURE 6.
A, full thickness defect of ala. Vertical height of defect is 1.5 cm; B, base view
shows loss of internal lining of ala. Vertical height of defect is 1.5 cm. (Continued.)

gives the flap an axial nature with an excellent blood supply. The
base is tapered superiorly to facilitate transposition and to reduce
the loss of skin from the upper portion of the melolabial fold where
the fold is more prominently manifested. A standing cutaneous de-
formity is marked distally so that the scar resulting from its exci-
sion will follow the line of the melolabial sulcus. The distal one
third of the flap is thinned, leaving 1 mm to 2 mm of subcutane-
ous fat in place. The donor site is closed primarily through
advancement. The pedicle is then divided 3 weeks later, at which
time the flap inset is partially elevated to allow for removal of ex-
cessive subcutaneous fat and scar from the proximal two thirds of
the covering flap. The flap is then trimmed of its tail of skin (car-
ried with it from the superior melolabial fold at the time of the ini-
tial transfer] and inset into the ala by joining it to the cheek skin
in the alar facial sulcus and to the nasal sill.

PARAMEDIAN FOREHEAD FLAP


A number of studies of the vascular anatomy of the forehead have
10
been reviewed by Baker and Alford. These studies confirm that
the supratrochlear artery is the primary axial blood supply of mid-
forehead flaps, which include the median and paramedian verti-
Contemporary Nasal Reconstruction 251

FIGURE 6. (cont.)
C, bipedicle vestibular mucosal flap is mobilized to provide lining to the defect.
A superiorly based subcutaneous pedicled interpolation flap is designed as a cov-
ering flap. T h e standing cutaneous deformity is excised distally in such a way
that the scar follows the melolabial and labiomandibular skin creases; D, flap in
position. Subcutaneous pedicle is visible at inferior border of flap. The pedicle is
divided 3 weeks after initial transfer. (Continued.)

cally oriented flaps. Additionally, the studies have shown that in


the medial canthal region, a rich anastomotic network exists be-
tween the supratrochlear, supraorbital, and angular arteries. Iden-
tification of this vascular network and the surgical techniques of
flap harvest that preserve this regional blood flow have allowed sur-
geons to harvest paramedian forehead flaps based on pedicles nar-
rower than those used for median forehead flaps. The narrower
pedicle gives the flap more freedom of transposition about its pivot
point, thereby providing more effective length. At the same time,
this design reduces the donor site deformity in the glabellar area
that results from transposition of the flap (Fig 7, D). Based on the
252 S. Baker

FIGURE 6. (cont.)
E, three months after surgery. Note normal contour of alar facial sulcus; F, auricu-
lar cartilage graft placed at time of reconstruction provides structural support,
maintaining a normal contour to the nostril.

supratrochlear artery and its anatomoses to surrounding vessels,


the paramedian forehead flap is an axial pivotal interpolation flap
with an outstanding blood supply that allows transfer without de-
lay. This highly vascular flap also allows primary incorporation of
cartilage or tissue grafts, which can then act as supporting struc-
tures.
Paramedian forehead flaps are the preferred local flap for re-
surfacing most large nasal defects. The flap can be dissected under
either local or general anesthesia. The base of the pedicle is placed
in the glabellar region centered over the supratrochlear artery on
the same side as the majority of the nasal defect. The origin of the
supratrochlear artery is consistently found to be 1.7 cm to 2.2 cm
lateral to the midline and corresponds usually to a vertical tangent
of the medial border of the brow. The vessel exits the orbit by pierc-
ing the orbital septum and passing under the orbicularis oculi and
over the corrugator supercilii muscle. At the level of the brow, the
artery passes through orbicularis and frontalis muscles and con-
tinues upward in a vertical direction in a subcutaneous plane. Be-
cause of this, the flap above the level of the brow all the way to
the hairline can be trimmed of its frontalis muscle and much of
the subcutaneous fat without harming the blood supply to the skin
of the covering flap. Because it is an axial flap based on a single
Contemporary Nasal Reconstruction 253

FIGURE 7.
A, full-thickness loss of ala and hemitip. Defect extends into medial cheek.
(Continued.)

supratrochlear artery, the pedicle of the flap may be as narrow as


1 1
1.2 c m . With such a narrow pedicle, there is a minimal standing
cutaneous deformity as the flap pivots. An exact template of the
defect is used to design the paramedian forehead flap, which is cen-
tered over the vertical axis of the supratrochlear artery. The length
of the flap is determined by measurement. If obtaining adequate
length necessitates extending the flap into the hair-bearing scalp,
the author prefers turning the flap obliquely along the hairline to
prevent transfer of hair-bearing skin to the nose. The flap is elevated
254 S. Baker

FIGURE 7. (cont.)
B, ipsilateral mucosal flap hinged on caudal septum provides internal lining to
ala and hemi-tip. This flap is detached from septum 3 weeks after initial transfer;
C, auricular cartilage grafts replace missing lateral crus and provides structural
support to ala. Septal cartilage graft (arrows) provides structural support to soft
triangle; D, paramedian forehead flap is used to provide covering flap. Cheek ad-
vancement flap repairs the cheek and lip defect. (Continued.)
Contemporary Nasal Reconstruction 255

FIGURE 7. (cont.)
E, one year after surgery; F, note restoration of alar-facial sulcus and nasoalar
crease.

in a subfascial plane just superficial to the periosteum of the fron-


tal bone. To avoid injury to the arterial pedicle, blunt dissection is
used near the brow to separate the corrugator muscle from the flap
and facilitate mobility. Incisions can be extended below the brow
if necessary to enhance the length of the flap. Adequate flap mobi-
lization usually requires complete sectioning of the corrugator su-
percilii muscle to achieve free movement. Prior to inset, the flap is
sculptured and contoured to fit the depth of the defect perfectly
by removal of all or some of the muscle and subcutaneous tissue
from the distal portion of the flap. When necessary, all but 1 mm
of fat beneath the dermis may be removed. It is sometimes even
necessary to resect a portion of the dermis along the edge of the
flap so that the thickness of the skin of the flap matches the adja-
cent nasal skin in instances where the adjoining nasal skin is quite
thin. Only the distal three quarters of the flap required for recon-
struction is sculptured; the proximal one quarter is left thick and
is debulked at the time of pedicle detachment 3 weeks later. Do-
nor site closure is accomplished by undermining the skin of the
256 S. Baker

forehead in the subfascial plane from the anterior border of one


temporalis muscle to the other. Several parallel vertical fascioto-
mies 2 cm to 3 cm apart may be helpful to achieve primary wound
closure. However, one must take care not to injure the supraorbital
nerves when initiating this maneuver. Any portion of the donor site
that cannot be closed primarily should be left to heal by second
intention, keeping the open wound moist at all times. Healing by
second intention usually results in an acceptable scar but may take
as long as 6 weeks for complete healing.
Three weeks after the initial flap transfer, the pedicle is divided
under local anesthesia. The nasal skin superiorly surrounding the
defect is undermined for approximately 1 cm. The portion of the
skin flap to remain attached to the recipient site, and not thinned
at the time of transposition, is now thinned appropriately. In the
case of reconstruction of skin-only nasal defects that extend to the
rhinion, the flap must be aggressively thinned to the level of the
dermis to duplicate the thin skin that is normally found in this area.
Deep-layer closure is not necessary, as the wound should not be
under any tension. The base of the pedicle is returned to the do-
nor site in such a way as to restore the normal anatomical and spa-
tial relationship of the two eyebrows. Care should be taken to main-
tain the muscular component of the proximal pedicle that is re-
turned so that a depression between the brows does not occur. Any
excess pedicle should be discarded rather than returned to the fore-
head above the level of the brow.

DEFECT CLASSIFICATION
Defects of the nose may be classified according to location, depth,
and size. The skin of the upper two thirds of the nose, columella,
and soft triangles is thin, nonsebaceous, and mobile. In contrast,
the lobule and ala are covered with immobile, thick, sebaceous
skin. Single-lobe transposition flaps may be satisfactory for smaller
defects of the upper nose because of the redundancy and mobility
of the skin covering the sidewall of the nose where the donor site
is located. They work less well for the nasal tip and poorly for the
ala because of secondary movement of adjacent free margins from
excessive wound closure tension. Full thickness skin grafts har-
vested from the preauricular area or forehead along the hairline
match the thickness and texture of the upper nose and if derm-
abraded postoperatively, often produce a satisfactory result. A skin
graft is also useful for limited defects of the columella and soft tri-
angles. Skin grafts are less favorable for the lobule and ala where
Contemporary Nasal Reconstruction 257

they may appear as an island or patch rather than blend in. If a


local flap is to be used for the inferior aspect of the nose, a bilobe
flap as modified by Zitelli is preferred for defects 2 cm or smaller
9
on the lobule or ala. This technique transfers adjacent skin into
the defect while repairing the secondary defect with a second lobe
harvested from the upper nasal sidewall in the area of slight skin
excess.
If the depth of a nasal defect extends through the supporting
framework, it must be restored with primary cartilage grafts, and a
covering flap harvested from the nose itself is no longer advisable
because contraction of such flaps often obscures the delicate topog-
raphy of the replacement framework. In such instances, a cheek or
forehead flap is the preferred covering flap. This approach replaces
the missing skin rather than borrowing it from another area of the
nose, keeping contracting forces of healing at a minimum. Full
thickness defects of the nose require replacement of the missing
lining with flaps harvested from the interior of the nose whenever
possible. These defects always require replacement of the missing
skeletal framework, and thus should be resurfaced with a parame-
dian forehead or melolabial interpolation flap.
The size of the nasal defect determines the source of the cov-
ering flap. In the case of defects larger than 2 cm in greatest di-
mension, there is rarely sufficient residual nasal skin for closure
by a local flap without creating undue wound closure tension.
Thus, the forehead or cheek should be used as a donor site.

RECONSTRUCTION OF COLUMELLA
The columella is the most difficult region of the nose to reconstruct.
Small defects limited to 1.5 cm in greatest dimension can occasion-
ally be repaired with composite grafts from the auricle in nonsmok-
ers. The grafts should be chilled for 3 days after transfer, and sys-
temic steroids should be administered for 1 week. Preferably, al-
low the initial defect to heal by second intention and then perform
the composite graft after preparing a fresh recipient site by remov-
ing all scar and neoepithelialization. The graft should be oversized
by 2 mm to accommodate wound contraction.
Larger defects of the columella are best repaired, depending on
the extent of the tissue loss, with unilateral or bilateral, superiorly
based, interpolated melolabial flaps. Septal cartilage grafts should
be used for the framework. The initial flap transfer will produce a
thick columella that will require secondary thinning. Defects that
extend into the lobule from the columella require structural sup-
port with cartilage grafts and a paramedian forehead flap for cover.
258 S. Baker

By extending the incision for the forehead flap into or below the
brow, the flap can be made to reach the upper lip without exces-
sive wound closure tension.
Full-thickness defects of the columella and lobule are best re-
constructed with a tilt-out, hinged composite nasal septal flap (Fig
3). Mucosa of the flap is peeled downward bilaterally to provide
internal lining. Auricular cartilage grafts are attached to the com-
posite flap to replace structural support laterally. A paramedian
forehead flap provides an exterior covering.

RECONSTRUCTION OF LOBULE
Small, skin-only superficial defects of the nasal tip, may be cov-
ered with a local bilobe flap or full-thickness skin graft. However,
a paramedian forehead flap will usually give a more natural result,
because the entire esthetic unit is covered by the flap, placing scars
in aesthetic unit boundaries. Cartilage grafts should be used rou-
tinely along the margin of the nostril when the defect extends from
the lobule into the soft triangle. This is in addition to any missing
lower lateral cartilage that must be replaced as well.
Bilateral full-thickness defects of the lobule should be repaired
with a tilt-out, hinged composite septal flap as discussed (Fig 3).
Unilateral full-thickness defects, however, can be nicely recon-
structed with an ipsilateral intranasal hinge mucosal flap (Fig 7).
This flap spans the nasal passage on the affected side to provide
internal lining to the hemitip. After restoration of the absent carti-
laginous framework, a paramedian forehead flap provides surface
replacement. In instances of a hemitip defect, I usually only resur-
face the hemidome rather than the entire lobule (Fig 7 ) . Concomi-
tant with detachment of the forehead flap 3 weeks after transfer,
the hinged mucosal flap is released from the septum, restoring pa-
tency of the nasal airway.

RECONSTRUCTION OF THE ALA


Defects confined to the ala with or without limited extension into
the lobule or sidewall are best resurfaced with an interpolated su-
periorly based melolabial flap (Fig 6). I routinely resurface the en-
tire ala regardless of the size of the alar defect. The melolabial flap
based on a subcutaneous pedicle is preferred, because this design
minimizes the amount of skin that must be removed from the up-
per melolabial fold. Preserving the upper fold is paramount in
maintaining symmetry of the cheeks after reconstruction of the ala
with a cheek flap. Cartilage grafts are used in the majority of alar
defects. This is because most lesions involving resection of skin
Contemporary Nasal Reconstruction 259

also require removal of the underlying thick subdermal tissue that


gives the ala form and structural support. This must be replaced
by cartilage to prevent upward migration of the ala and notching
of the margin of the nostril. Internal lining for full-thickness alar
defects is provided by bipedicle vestibular skin flaps or unilateral
hinged septal mucosal flaps. Occasionally, an additional contralat-
eral hinged mucosal flap, as discussed in the earlier portion of this
chapter, may be necessary if the vertical height of the defect is such
that a single hinged mucosal flap will not provide sufficient tissue
to replace the entire missing lining.

RECONSTRUCTION OF THE NASAL DORSUM


The nasal dorsum is perhaps the least complex portion of the nose
to reconstruct. The forehead flap is usually preferred to resurface
skin-only defects of the lower dorsum; however, bilobe flaps or full-
thickness skin grafts may also be used. Likewise, skin defects of
the upper dorsum can be repaired with glabellar flaps, such as the
dorsal nasal flap or full thickness skin grafts, but paramedian fore-
head flaps are preferred. Small defects of the framework of the dor-
sum can be replaced with septal cartilage grafts. More extensive
defects of the nasal skeleton extending from the frontal bone to the
lobule are best replaced with calverial bone grafts secured to the
frontal bone or remaining nasal bony root with plate-and-screw
fixation.
To prevent medialization of the nasal sidewall after wound
healing, structural defects that extend into the nasal sidewall re-
quire replacement concurrent with replacement of the dorsal
framework. Septal cartilage or additional cranial bone grafts se-
cured to the dorsal graft work well for this purpose. Internal lining
for full thickness dorsal defects can usually be provided by muco-
sal hinge flaps reflected laterally from the dorsum, as long as there
is sufficient height to the remaining septum. Unilateral or bilateral
hinge septal mucosal flaps based on the caudal septum and includ-
ing the septal branch of the labial artery can also be used sometimes
for lining when there is considerable loss of the dorsal septum. A
tilt-out composite septal flap, as discussed earlier in this chapter,
should be used to provide lining and structural support for the dor-
sum in extensive bilateral full thickness dorsal nasal defects. In in-
stances when this approach will not provide sufficient tissue, bilat-
eral paramedian forehead flaps are recommended. One flap pro-
vides internal lining and the other provides external coverage. A
cranial bone graft is placed between the flaps for structural support.
260 S. Baker

RECONSTRUCTION OF THE SIDEWALL OF THE NOSE


Reconstruction of the sidewall of the nose is relatively uncompli-
cated. Small, skin-only defects may be repaired with a bilobe flap
harvested from the remaining nasal sidewall skin. Full-thickness
skin grafts harvested from the preauricular area of the cheek also
provide a reasonable option for covering defects located in the su-
perior portion of the sidewall, because of the thin skin in this lo-
cation. Larger surface defects are best covered with a paramedian
forehead flap. When structural support is absent from the upper
one third of the sidewall of the nose, it should be replaced with a
calverial bone graft, whereas the lower two thirds of the sidewall
skeleton is best replaced with septal cartilage grafts. Unilateral de-
fects of the sidewall of the nose can be lined using contralateral
hinged septal mucosal flaps based on the nasal dorsum and deliv-
ered through a superiorly positioned nasal septal fenestrum. For
more inferiorly located defects, a unilateral mucosal flap hinged
on the caudal septum may provide sufficient lining. This arrange-
ment, however, requires subsequent detachment of the pedicle. It
is usually necessary to use both the contralateral, dorsally based
flap and the ipsilateral, caudal septal-based hinged mucosal flap
to provide lining for full-thickness defects that extend the entire
length of the nasal sidewall.

SUMMARY
Reconstruction of the nose has progressed during the last decade
to a new level of finesse that allows the surgeon to restore near-
normal form and function to all but the most extensive defects of
the nose. These advances are based on the contemporary concepts
of respecting the borders of aesthetic units of the nose. The nose is
reconstructed separately from any extension of nasal defects onto
the cheek or lip, which in turn are repaired by tissue within their
respective aesthetic regions. The other concept that has contributed
to this higher level of surgical achievement is the replacement of
missing tissue with like tissue. Internal lining is replaced with na-
sal mucosal flaps that, because of their nature, provide adequate
vascularity to nourish and sustain the cartilage and bone grafts
used in skeletal replacement. Missing bone and cartilage are
replaced with similar tissue, which is carefully crafted to replicate
the exact size, configuration, and contour of the missing nasal skel-
eton. Surface defects are covered with cheek or forehead skin trans-
ferred by interpolation so as not to violate the aesthetic boundary
between the nose and the other regions of the face. This surgical
Contemporary Nasal Reconstruction 261

approach provides natural building material precisely fitted to al-


low nasal deficits to be reconstructed to a condition as nearly nor-
mal as possible.

REFERENCES
1. Goepfert H, Arredondo R, McNeese MD: Cancers of the skin of the
nose. Otolaryngol Head Neck Surg 9 0 : 2 3 4 - 2 4 0 , 1982.
2. Barton FE Jr, Cottel WI, Walker B: The principle of chemosurgery and
delayed primary reconstruction in the management of difficult basal
cell carcinomas. Plast Reconstr Surg 6 8 : 7 4 6 - 7 5 2 , 1 9 8 1 .
3. Baker SR, Swanson NA: Management of nasal cutaneous malignant
neoplasms: An interdisciplinary approach. Arch Otolaryngol 1 0 9 : 4 7 3 -
4 7 9 , 1983.
4. Baker SR, Swanson NA: Reconstruction of midfacial defects follow-
ing surgical management of skin cancer: The role of tissue expansion.
J Dermatol Surg Oncol 2 0 : 1 3 3 - 1 4 0 , 1994.
5. Baker SR, Swanson NA, Grekin RC: Mohs surgical treatment and re-
construction of cutaneous malignancies of the nose. Facial Plast Surg
5:29-47, 1987.
6. Burget GC, Menick FJ: Nasal support and lining: The marriage of
beauty and blood supply. Plast Surg 8 4 : 1 8 9 - 2 0 3 , 1989.
7. Menick FJ: Reconstruction of the nose, in Baker SR, Swanson NA
(eds): Local Flaps in Facial Reconstruction. St. Louis, Mosby, 1995,
pp 3 0 5 - 3 3 7 .
8. Burget GC, Menick FJ: Aesthetic Reconstruction of the Nose. St. Louis,
Mosby, 1 9 9 3 .
9. Zitelli JA: Bilobe flaps, in Baker SR, Swanson NA (eds): Local Flaps
in Facial Reconstruction. St. Louis, Mosby, 1995, pp 1 6 5 - 1 8 0 .
10. Baker SR, Alford EL: Mid-forehead flaps: Operative techniques. Oto-
laryngol Head Neck Surg 4 : 2 4 - 3 0 , 1993.
1 1 . Menick FJ: Aesthetic refinements in use of the forehead flap for nasal
reconstruction: The paramedian forehead flap. Clin Plast Surg 1 7 : 6 0 7 -
622, 1990.
CHAPTER 13
Anesthesia for the
Pediatric Otolaryngic
Patient
Jimmy Scott Hill, M.D
Fellow, Department of Pediatric Otolaryngology, University of Pittsburgh
School of Medicine and Children's Hospital of Pittsburgh, Pittsburgh,
Pennsylvania

Peter J. Davis, M.D.


Professor of Anesthesiology and Pediatrics, University of Pittsburgh
School of Medicine and Children's Hospital of Pittsburgh, Pittsburgh,
Pennsylvania

A s surgical procedures advance the frontiers of medicine, the


practice of pediatric anesthesiology also has become complex
and highly specialized. The role of the pediatric anesthesiologist
cannot be understated. Studies reporting anesthesia morbidity and
mortality have consistently demonstrated that infants and small
children have a significant risk of anesthesia-related complications.
In the 1950s to 1960s, the mortality rate for infants and children
1 4
was reported to be 6.3 to 16.2 per 10,000 pediatric patients. " More
recent data suggest that the incidence of cardiac arrest in children
5
is less than 2.5 per 10,000 patients, but the incidence of adverse
anesthesia-related events is still significantly greater than the rate
for adults. Although the age of the patient and the severity of the
patient's illness are key factors, the role of specialized training in
6-8
pediatric anesthesia appears to be equally i m p o r t a n t .
The anesthetic management of children requires a thorough
preoperative evaluation and formulation of an anesthetic plan. For
the child having an otolaryngic procedure, the patient's airway is
frequently shared between the surgeon and anesthesiologist. Thus,
communication between surgeon and anesthesiologist is essential
for good clinical care. In this chapter, we discuss the anesthetic
concerns for children undergoing otolaryngic procedures. We also
Advances in Otolaryngology-Head and Neck Surgery", vol.12
b
° 1 9 9 8 , Mosby, Inc. ^ *>
264 J.S. Hill and P.J. Davis

address specific disorders frequently encountered by the otolaryn-


gologist.

GENERAL PREOPERATIVE EVALUATION


The preoperative evaluation of the pediatric patient requires the
cooperation of the primary care physician, surgeon, and anesthe-
siologist. The preoperative assessment usually begins with the pri-
mary care physician and should include a general physical exami-
nation and a statement about the child's medical condition. For
those children with underlying disorders such as asthma or cystic
fibrosis, comments should be made as to whether the patient's
medical condition has been optimized. Although the role of the pri-
mary care physician is paramount in the preparation of the patient,
it should not be relied on alone. It is the role of the surgeon and
anesthesiologist to coordinate and complete the patient's preopera-
tive evaluation. With trends toward outpatient surgery, it is increas-
ingly important for the surgeon to assess accurately a child's likely
operative and postoperative course.

PREOPERATIVE EVALUATION
PSYCHOLOGICAL
The preoperative period is an extremely stressful time for both the
9
child and the parent. During this time, the anesthesiologist and/or
otolaryngologist must be able to address the child's otolaryngic dis-
order and other preexisting medical conditions, as well as the
child's and family's psychological and emotional needs. The goals
of the preoperative evaluation are, first, to alleviate the anxiety of
the parent and child, and second, to obtain an adequate medical
history and do a good physical examination. Preparation before ad-
mission to the hospital varies with the age of the child. Psychologi-
cal preparation of the child is paramount and must be tailored to
the individual according to his or her age. It is important that pri-
mary health care providers participate in the medical evaluation
10
and psychological preparation for a procedure. The psychological
11
reaction of the child can be separated into five basic fears : the fear
of separation from parent, the fear of physical harm or pain, the fear
of the unknown, the uncertainty of expectations or fear of punish-
ment, and the fear of loss of control, privacy, or autonomy.
Not every child will experience every reaction, but age groups
tend to exhibit fairly typical reactions. Clinically, the young infant
probably represents the greatest challenge to the physician. Be-
cause these children do not yet exhibit anxiety about strangers, the
Anesthesia for Pediatric Otolaryngic Patient 265

psychological problems in this age group are probably minimal, al-


12
though some authors dispute t h i s . It is important to minimize the
disruption to the young infant's normal feeding pattern. Premedi-
cation is generally not necessary in this age group. Older infants
and children between the ages of 6 months and 4 years are par-
ticularly vulnerable to the psychological stresses of surgery. They
frequently experience fears of the unknown, harm, and separation
anxiety. They often make predictions (such as anticipating pain)
from prior experiences, but unfortunately, children of this age are
generally incapable of reason. They may have postoperative diffi-
culties related to these fears. The school-aged child and teenager
tend to be more anxious about the loss of control and fear of bodily
harm or disfigurement. They are frequently very concerned about
self image.
Honesty is of utmost importance in order not to undermine
credibility and trust with the patient. Discussions should take
place close to the time of the surgical procedure and should be
appropriately broad and general. These discussions should be
geared to eliminate the fear of the unknown. Many centers have
videos or tours to familiarize the child with the operating room
and to make the child more comfortable. This helps to establish
the patient-doctor relationship. One should always focus on the
child in conversations with the family to gain access to the
child's "inner circle." The process should be discussed in child-
friendly terms, avoiding language with negative connotations
such as "put to sleep." Descriptions of the postoperative course
should be emphasized and concerns about postprocedure pain
should be addressed. Within reason, attempts should be made to
give the child choices. It is important in the care of children to
remain flexible. It is imperative that the pediatric anesthesiologist
and otolaryngologist be able to answer intelligently the questions
of the parents.

PHARMACOLOGY
Even with appropriate psychological preparation, a large number
of children will need preanesthetic medication to allay their anxi-
ety. For children, there are numerous options, as well as a vast ar-
ray of methods to administer these preanesthetic medications. In
some ways, the route of drug administration is just as important as
the drug itself. The different routes of administering preanesthetic
medications to children include intravenous (IV), intramuscular
(IM), oral (ingested), and transmucosal (nasal, rectal, or buccal)
(Table 1).
TABLE 1.
Dosage of Common Premedicant Drugs

Route of Administration

Oral
Class Drug per kg Oral IM Nasal Rectal Transmucosal Sublingual IV
ANTICHOLINERGICS Atropine mg .02-.04 .02-.03 — — — .02-03 .01-02
Glycopyrolate mg — 0.01 — — — — 0.005
Scopolamine mg — 0.01 — — — — 0.01
OPIOIDS Fentanyl M-g — 1-2 — — 10-15 — 1-2
Meperidine mg 2-3 1-2 — — — — .5-1
Morphine mg .1-.2 .1-.2 — .1-2 — — .05-1
Sufentanil M-g — ,2-.6 1.5-3.0 — — — —
BARBITURATES Methohexital mg — 7-10 — 20-30 — — .25-1
Pentobarbital mg 2-6 3-5 — 3.5 — — —
Secobarbital mg 2-6 3-5 — 4-5 — — —
Thiopental mg — — — 30 — — 1-2
SEDATIVE-HYPNOTICS Chloral hydrate mg 30-50 — — — — — —
Diazepam mg .1-2 — — .5-.75 — — .05-.1
Ketamine mg 3-6 2-3 3-6 5-10 — — .2-.3
Midazolam mg .5-1 .1-.2 .2-. 3 .3-1 — .1-.2 .07-.1
Propofol mg — — — — — — .3-. 6
Triazolam mg 0.02 — — — — — —
Triclofos mg 70 — — — — — —
ALPHA 2 AGONISTS Clonidine mg 4 — — — — — —

Abbreviations: kg, kilogram; mg, milligram; \xg, microgram; IM, intramuscular; IV, intravenous.
Anesthesia for Pediatric Otolaryngic Patient 267

Although the pharmacologic types, combinations, and routes


of administration of preanesthetic medications are vast, there are
four main principles that need to be remembered when one con-
siders the use of preanesthetic medication in children:

1. Children fear needles and intensely dislike injections.


2. It is essential that the anesthesiologist deal openly and hon-
estly with the child's fears and concerns.
3. Timing of the preanesthetic medication is essential. Adminis-
tering a fast-acting agent for a procedure that will not take place
for hours makes little sense. Conversely, administering a slow-
onset drug for a procedure that will begin immediately offers
no benefit to the child.
4. Children remember past experiences and know what they do
and do not like. All one has to do is take the time to ask them.
Thus, preanesthetic medications and their routes of adminis-
tration need to be individualized to the patient. However, fre-
quently it is institutional preference that determines what pre-
anesthetic medication and what route of administration will be
used in children.

REGARDING FASTING
Questions regarding fasting requirements occur frequently with pe-
diatric patients. Recently, guidelines for preoperative oral intake
have undergone extensive changes. Studies have shown that intake
of a clear liquid up to 2 to 3 hours before anesthesia does not sig-
nificantly change the volume in the stomach or alter the pH of gas-
1 3 - 1 5
tric c o n t e n t s . Clear fluids 3 hours before surgery do not affect
1 6 , 1 7
the gastric fluid contents of c h i l d r e n . We currently recommend
that children be allowed to have clear liquids freely until 3 hours
before induction. The fasting period after ingestion of solids is 6
hours. Each hospital will have its own policy, and the physician
involved should know the hospital policy when discussing fasting
requirements with the family.

BLOOD TRANSFUSION
A frequent question regards the risk to the child who requires a
blood transfusion. Each situation should be handled according to
the type of procedure to be performed and the surgeon's or anes-
thesiologist's experience in frequency of transfusion. Although au-
tologous donation is an option for children, this is frequently not
possible because of body size. Other alternatives, such as the use
of directed donor blood, are controversial because of the associ-
268 J.S. Hill and P.J. Davis

ated risk factors. Although assurances may be made, a surgeon or


anesthesiologist should never promise the parent that blood trans-
fusions will not be given. Special situations, such as those involv-
ing Jehovah's Witnesses should be contemplated before schedul-
ing the surgery.
Jehovah's Witness (JW) patients are not willing to accept blood
products even at risk of death. Most state laws respect this right to
refuse blood transfusion in the adult, but this is a very controver-
sial issue in children. The interpretation of the law in the case of
children is often confusing or contradictory. Most state laws sup-
port the use of blood products in Jehovah's Witness children as a
life-saving measure, but they are less clear about their use in other
situations. Because of this, the surgeon should be extremely cau-
tious about performing elective procedures in JWs when there are
alternative treatment methods. There is no surgery that is free of
risk of life-threatening hemorrhage. In the case of hemorrhage in
the JW patient, measures such as l-deamino-8-D-arginine vasopres-
sin (DDAVP), erythropoetin, cell saver, maximization of oxygen uti-
lization, or use of blood substitutes may be useful.

SURGICAL RISK
It is the primary task of the anesthesiologist to speak in detail to
the parent about risk directly related to the anesthesia (e.g., dental
trauma, postoperative apnea, drug reaction, aspiration pneumonia,
hypoxemia, malignant hyperthermia, cardiac arrest, death, and
10
brain i n j u r y ) . The discussion of potential complications specifi-
cally related to the procedure itself should be discussed by the
surgeon.

HISTORY
The history of the child's present illness is usually the first por-
tion of the interview. The medical evaluation should include a
survey of the patient's general health, as well as specific health
problems, including previous surgical procedures. A history of pre-
vious anesthetic experiences and problems such as nausea, vomit-
ing, or muscle weakness should be noted. It is also important to
note a family history of such problems. Any medical problems
should be noted, especially cardiac and respiratory disease. Aller-
gic history, both drug and environmental, should be sought.
Patients at increased risk for untoward reactions should be duly
noted. One example of this is the increased incidence of latex
allergy in patients with meningomyeloceles or in those who self
18
catheterize.
Anesthesia for Pediatric Otolaryngic Patient 269

Pertinent laboratory tests to assess the hematologic, renal,


metabolic or pulmonary status should be individualized for each
patient. The role of pregnancy tests for adolescents is controversial.
Hemoglobin and coagulation studies should be obtained when ei-
ther the history or medical condition suggest a possible hemostatic
defect, when the surgical procedure may induce a hemostatic disor-
der, or when the coagulation system is particularly necessary for
hemostasis (e.g., tonsillectomy). There is considerable debate re-
garding the need and reliability of coagulation studies in predicting
19 21
intraoperative or postoperative b l e e d i n g . " The need for hemato-
22 25
logic studies in most patients has likewise been c h a l l e n g e d . "
Medications that the patient is or has been taking, as well as their
possible interactions, should be documented. The patient's compli-
ance with medications should be noted. The presence or suspicion
of a syndrome is important because of the risk of multiple anoma-
lies. The nulla per os (NPO) status should be noted. A comprehen-
sive review of systems should be performed along with an appro-
priate physical examination. The key to the successful administra-
tion of anesthesia begins with an appropriate patient assessment
and the anticipation of potential perioperative problems.

ANESTHETIC INDUCTION
The anesthesiologist should discuss various methods of adminis-
tering the anesthetic with each family, and the patient should
participate in the choice as much as possible. For children,
induction of anesthesia is accomplished with inhaled or intrave-
nous anesthetic agents. Inhaled inductions obviate the need for
needles and catheters being placed in awake patients. Although
intravenous access in an awake child can be traumatic, the role of
EMLA cream (Astra, USA, Inc; Westborough, MA) has signifi-
cantly removed the pain but not the fear of needle injections.
EMLA cream, a eutectic mixture of lidocaine and prilocaine, can
penetrate intact skin to provide topical analgesia when applied to
the site and covered with an occlusive dressing for at least 60
minutes.
In children, inhaled inductions are accomplished with nitrous
oxide along with either halothane or sevoflurane in a scented mask.
In clinical trials, sevoflurane, with its low solubility, allows for
26-28
faster induction than h a l o t h a n e . In addition, it has fewer nox-
ious airway properties and provides less myocardial depression
29
than halothane.
270 J.S. Hill and P.J. Davis

In children who undergo intravenous induction, an intrave-


nous catheter is inserted. However, the first requirement of intra-
venous anesthesia is having a functioning IV. The most common
intravenous induction agents include propofol and thiopental.
Thiopental is a water-soluble barbiturate and can induce uncon-
sciousness in less than a minute. Propofol is a water-insoluble drug
and it, too, produces unconsciousness in less than a minute. Be-
cause of its redistribution and elimination properties, recovery
from propofol anesthesia tends to be fast. Propofol is also thought
to have antiemetic properties. Propofol's major disadvantage is the
pain it induces when administered into small vessels.
Intramuscular injections for anesthetic induction are rarely
used. The one exception is the belligerent child. In the physically
abusive and uncooperative child, intramuscular ketamine can fa-
cilitate an inhalation induction in low doses (3 mg/kg), or induce
anesthesia in high doses (6—10 mg/kg). The disadvantages of keta-
mine are that, upon administration it can produce copious secre-
tions, and in the postoperative period, it can produce hallucina-
tions and bad dreams.
The role of parents in pediatric anesthesia induction is contro-
versial. Although more than 3 decades ago Schulman noted that
surgical patients aged 2 to 6 years who were accompanied into the
30
operating room by a parent appeared to be c a l m e r , Bevan et al.
noted that parental presence at induction of anesthesia may not be
helpful to all children. In this study, Bevan noted that calm par-
31
ents created calm c h i l d r e n . The most upset children at induction
were those with anxious parents. Each institution has its own prac-
tices. If parents are allowed to participate in their child's induc-
32 34
tion, it is essential that they be prepared for the e v e n t . "

AIRWAY MANAGEMENT
For all but the shortest procedures, intubation of the patient's tra-
chea is usually performed for otolaryngic procedures. For routine
procedures, the trachea is intubated with the aid of a nondepolar-
izing muscle relaxant (vecuronium, cisatracurium, mivacurium,
pancuronium). If muscle relaxants are to be avoided, the patient is
deeply anesthetized and the vocal cords are sprayed with 1% xy-
locaine. T h e endotracheal tube size is selected based on the
patient's age and weight (Table 2).
Because many otolaryngic patients are anesthetized to further
evaluate the airway, a different approach to the airway and the ad-
ministration of the anesthetic agents must be used. Because the air-
way is shared between the anesthesiologist and otolaryngologist,
Anesthesia for Pediatric Otolaryngic Patient 271

TABLE 2.
Endotracheal Tube Size

Inner diameter
Age Weight (kg) (mm)
Premature 0.7--1.0 2 5
Premature 1.0--2.5 3 0
Newborn 2.5--3.5 3 5
3 months 3.5--5.0 3 5
3—9 months 5.0--8.0 3 5-4.0
9 - 1 8 months 8.0--11.0 4 0-4.5
1.5—3 years 11.0--15.0 4 5--5.0
4—5 years 15.0--18.0 5 0--5.5
6—7 years 19.0--23.0 5 5--6.0
8—10 years 24.0--30.0 6 0--6.5
1 0 - 1 1 years 30.0--35.0 6 0--6.5*
1 2 - 1 3 years 35.0--40.0 6 5--7.0*
1 4 - 1 6 years 45.0--55.0 7 0--7.5*
* Cuffed tube

communication of both the anesthetic plan and the surgical plan


is essential. This communication must occur before the onset of
anesthesia. (It is of no use to have a patient paralyzed with a non-
depolarizing muscle relaxant if vocal cord mobility is to be
assessed.)
In patients with acquired or congenital anatomical airway ab-
normalities, the induction of anesthesia can exacerbate any under-
lying airway compromise. If airway obstruction occurs with severe
compromise to the patient's ability to be oxygenated and venti-
lated, the preoperatively constructed algorithm of the surgeon and
anesthesiologist needs to be instituted. Because airway problems
in otolaryngic patients are common and frequently life threaten-
ing, it is imperative that the surgeon be present for the anesthetic
induction in these patients. In those children with a tracheostomy
tube already in place, anesthesia is usually induced with inhaled
anesthetic agents.

MAINTENANCE ANESTHESIA
Like induction, the maintenance of anesthesia can be achieved
with the use of either inhaled or intravenous anesthetic agents. Ni-
trous oxide is the most frequently used inhaled anesthetic agent.
272 J.S. Hill and P.J. Davis

Its low potency limits its use as a sole anesthetic agent. Conse-
quently, nitrous oxide is used in combination with more potent in-
haled anesthetic agents, such as sevoflurane, halothane, isoflurane,
or desflurane. Nitrous oxide is relatively insoluble and has no car-
diovascular depressant effects. In contrast, the more potent inhaled
anesthetic agents have significant cardiovascular depressant ef-
fects. Thus, the addition of nitrous oxide to the administration of
the other agents attenuates the cardiovascular depressant effects of
the more potent inhaled anesthetic agents while adding to the an-
esthetic potency of the administered drugs. Generally, the choice
of anesthetic agents relates to their relative cardiovascular depres-
sant effects, their affects on airway irritability, and their ability to
readily induce anesthesia and hasten the emergence and recovery
from anesthesia (Table 3).
The choice of intravenous agents for maintenance of anesthe-
sia includes the nonbarbiturate hypnotic agents such as propofol
and the opioids. Propofol is an alkyl phenol whose rapid redistri-
bution and elimination produce a short duration of action and al-
low the drug to be administered by repeat injections or continu-
ous infusion. In addition to its anesthetic properties, propofol also
has antiemetic properties in pediatric patients undergoing otolar-
35
yngic procedures.

TABLE 3.
Comparative Effects of the Inhaled Anesthetic Agents in Children

Property Halothane Isoflurane Desflurane Sevoflurane


Induction ++ + 0 +++
characteristics
Hemodynamic + +++ ++ +++
stability
Respiratory stability +++ ++ ++ +++
Ability to titrate + ++ +++ +++
Emergence, rate of 0 + +++ ++
recovery
Postoperative side + + ++ ++
effects
Potential 0 ++ +++ +
toxicity/
metabolism
Scale: 0, worst; + + + , best
Anesthesia for Pediatric Otolaryngic Patient 273

The opioids are an interesting class of drugs that provide in-


traoperative anesthesia and postoperative analgesia. The classic
drugs used in anesthesia include morphine, meperidine, and fen-
tanyl. All of these agents are metabolized in the liver and have a
half-life of 2 to 4 hours.
Remifentanil is a new opioid that has become available for
clinical use. Remifentanil has the same potency as fentanyl, but
unlike the other opioids, remifentanil undergoes tissue and plasma
esterase metabolism. It has a half-life of 7 to 10 minutes; conse-
38 37
quently, it must be administered by continuous i n f u s i o n . ' Be-
cause of its short half-life and its mode of metabolism, remifentanil,
unlike other opioids, does not accumulate with repeat bolus injec-
tions or prolonged continuous infusions. However, as with other
opioids, remifentanil has a similar incidence of postoperative nau-
sea and vomiting. Although remifentanil's short half-life makes it
a very predictable drug to administer and lessens the chance of
postoperative respiratory depression, its short half-life precludes
its use as a postoperative analgesic. Thus, for patients in whom
postoperative analgesia will be necessary, additional opioids or
nonsteroidal anti-inflammatory drugs must be given.

SPECIAL PROBLEMS IN PREOPERATIVE EVALUATION OF


OTOLARYNGIC PATIENTS
Otolaryngologists are frequently confronted with patients who
have either a chronic illness or medical condition requiring spe-
cial evaluation and preparation from both the surgical and anes-
thetic perspective. In addition, probably no other specialty has
more patients present for surgical procedures on an elective basis
that have acute infectious or active medical problems. Because of
this, it is imperative that both the otolaryngologist and the anes-
thesiologist be well versed in the potential complications and
safety issues surrounding these acute and chronic disorders. In the
following discussion, some of the disorders most commonly seen
in conjunction with otolaryngic surgical procedures will be dis-
cussed. An attempt will be made to address the most important
concerns, allowing the otolaryngologist to be educated regarding
these disorders and their anesthetic risk.

PULMONARY
Upper Respiratory Infection
Otolaryngologists are frequently confronted with the dilemma of
proceeding with an elective surgical procedure on a child with an
274 J.S. Hill and P.J. Davis

upper respiratory infection (URI). Most children have between


58
three and eight URIs per y e a r . It has been a common practice to
cancel surgical procedures in patients with an active upper respi-
ratory infection because of the associated increased risk of intra-
operative complications and perioperative morbidity. Cancellation
of procedures is very upsetting for parents and children. It also is
costly in terms of money and time for both the physicians and fami-
lies involved. However, it is imperative that the anesthesiologist
and surgeon make the appropriate decision for the safety of the
9
c h i l d . ' Studies have shown that anesthesiologists who have been
in practice for more than 10 years are significantly more likely to
cancel a surgical procedure for upper respiratory tract infection
39
than those practicing fewer than 10 y e a r s . For many anesthesi-
ologists, it is standard practice to avoid general anesthesia for elec-
tive surgery in children with a URI because of multiple anecdotal
40-44
reports of respiratory c o m p l i c a t i o n s . Evaluation by others sug-
gests that there is no difference in risk for certain procedures in
4 0 4 2 4 5 - 4 8
children with a U R I . ' '
Patients with a URI have been shown to have increased alveo-
40
lar arterial gradient; increased incidence of postoperative hypox-
45 48,49
e m i a ; an increased risk for b r o n c h o s p a s m ; and an increased
42,50
incidence of l a r y n g o s p a s m . In evaluating the patient with a re-
spiratory infection, it is essential to differentiate a URI from a lower
respiratory infection. It has been suggested that there is no increase
in the anesthetic complication rate in patients with URI, as
opposed to patients with active lower respiratory infection, or
46
those with a recent U R I . However, other studies suggest that pa-
tients with either upper respiratory or lower respiratory infections
are at increased risk of bronchospasm, stridor secondary to sub-
40-44
glottic edema, hypoxia, and a t e l e c t a s i s . Rolf and Cote sug-
gested that complications associated with mild URIs were easily
48
treated and did not cause any significant long-term morbidity. Co-
hen and Cameron also showed that age was a factor associated with
complications in children with URIs. In children younger than 2
years of age, bronchospasm and laryngospasm were common in
42
those with U R I s .
It is obvious from the literature that there is no definite answer
to URI and the cancellation of general anesthesia. The decision
making for the administration of general anesthesia in children
with upper respiratory infection should be a team effort. The pri-
mary concern should always be for the child's safety, and only af-
ter this safety is ensured can secondary concerns such as inconve-
nience and cost be entertained. If the surgery is nonelective, then
Anesthesia for Pediatric Otolaryngic Patient 275

FIGURE 1.
Algorithm for clinical decision making in URI. (From Martin LD: Anes-
thetic implications of an upper respiratory infection in children. In Wet-
zel RC, editor: Pediatr Clin North Am 4 1 : 1 2 1 , 1994.)

the goal of the anesthetic evaluation is to recognize potential com-


plications before proceeding with the anesthetic and to be prepared
should they occur. For patients undergoing elective procedures, the
anesthesiologist and surgeon should be ready to deal with signifi-
cant pressure from the parents. Parents often have taken time from
work for the procedure. The distance that the parents have trav-
eled and a fear of litigation may influence physicians involved;
however, those factors should have no role in the decision-making
process. Although the attitude of the family regarding cancellation
of the procedure plays a vital role in the final decision, it should
never supersede the child's welfare. Fig 1 is a recommended algo-
rithm for clinical decision making in children with a URI. Systemic
signs and symptoms include high-grade fever, productive cough,
or abnormal pulmonary examination. However, short procedures
such as myringotomy and tympanostomy tube insertion are usu-
276 J.S. Hill and P.J. Davis

ally well tolerated in the patient with localized upper respiratory


46
symptoms.
If the procedure is canceled, when should it be rescheduled?
There are no good studies to show how long one should wait after
a respiratory infection before administering an anesthetic. The
usual approach is to postpone the surgery for 1 to 2 weeks after
symptoms of the URI have resolved. However, Empey has shown
that patients with a recent URI have altered airway reactivity for
51
up to 6 weeks after the infection. The mechanism for this may
be increased leukotriene, bradykinin, or histamine release. Tait
has shown that patients who have just recovered from URIs may
be at slightly increased risk compared with those with actual
46
active risk for infection. A more conservative approach may be
to postpone elective procedures for 4 to 6 weeks after resolution
of symptoms.

Asthma
Asthma and cystic fibrosis are the most common chronic pulmo-
nary diseases of childhood. It appears that the incidence of asthma
52 54
is i n c r e a s i n g . " It is known that various environmental factors
precipitate airway hyperactivity and trigger asthma. Familial pre-
52 55
disposition appears to be the strongest such factor. ' Some of
the environmental factors that may trigger the development of air-
56
way hyperactivity are viral lower respiratory i n f e c t i o n s , chronic
mechanical ventilation, and congenital diaphragmatic hernia re-
5 7 - 6 0
pair. Other factors include prematurity, gastroesophageal re-
6 1 - 6 3
flux, and parental or patient s m o k i n g . Although most children
are not routinely symptomatic from asthma, URIs or another ill-
ness can exacerbate their underlying airway hyperreactivity.
The pathophysiology of asthma can be described as a chronic
inflammation of the airway secondary to mast cell and eosinophilic
release of cytokines, lipid mediators, and preformed substances
64
of inflammation. The release of these inflammatory mediators re-
sults in increased airway inflammation with mucosal edema and
hypersecretion of mucous. This increased mucous may result in
focal atelectasis and air trapping. The subsequent ventilation-
perfusion inequality may result in hypoxemia and hypercapnia and
in the worst situations may cause respiratory failure. Signs and
symptoms include bronchospasm responsive to bronchodilator
therapy, expiratory wheezes, decreased air movement, cyanosis
65
and/or hypoxemia, and pulses paradoxes. Symptoms of asthma
range from none to wheezing, coughing, dyspnea, and respiratory
distress.
Anesthesia for Pediatric Otolaryngic Patient 277

Five classes of drugs may be used in medical therapy for


asthma. The first class, and the mainstay of treatment, are the beta
2 agonists. These compounds act on the airway smooth muscle by
increasing adenylate cyclase activity. This increases cyclic adeno-
sine monophosphate (AMP) and consequently promotes smooth
muscle relaxation and bronchial dilation.
The second category of medicines is the methylxanthines.
These compounds work by blocking the phosphodiesterases
from breaking down cyclic AMP (cAMP). In the past, the methyl-
xanthines were the most common asthmatic therapy. They have
fallen somewhat into disfavor in recent years because more
efficacious and safer medicines with fewer side effects are avail-
53 6 6 - 6 9
able. ' Methylxanthines have a synergistic effect with the
70
beta 2 agonists.
The third group of drugs is the anticholinergics, including
ipratropium bromide. Ipratropium can be used as either an inhaler
or a nebulizer. It has a slower onset of action than the beta 2 ago-
nist drugs, but ipratropium has a longer duration of action. Cro-
molyn sodium is a fourth group of medicines for treatment of
asthma. Cromolyn is a mast cell stabilizer and thus is useful in a
preventative or prophylactic manner. Sodium cromolyn must be
taken daily. Cromolyn results in mast cell stabilization and reduces
71
the release of IgE antibody-mediated compounds.
The fifth group of medicines is corticosteroids. These should
be reserved for the most severe asthmatics; however, it is reason-
able to give any patient with asthma with recent exacerbation or
current active disease a pre-operative dose of intravenous steroids.
If the patient takes systemic steroids chronically, he or she should
receive a stress dose of steroids. Hydrocortisone hemisuccinate
(Solucortef), given 2 mg/kg intravenously immediately preopera-
tively, is currently the recommended coverage for adrenal insuffi-
ciency secondary to prolonged steroid use. A dose should also be
given every 6 hours on the day of the surgery, with continuing
doses postoperatively throughout the period of increased physi-
ologic stress. Other regimens include the preinduction dose of
2
25 m g / m of hydrocortisone followed by continuous infusion of
2
50 m g / m during the anesthetic, as well as 24 hours postopera-
tively. The effects of inhaled steroids on the adrenal-pituitary axis
are controversial. Most physicians do not feel that a stress dose of
steroids is mandatory in patients using steroid inhalers. Most
would administer intravenous steroids to these asthmatic patients
to assist in management of their asthma, so the issue is probably
moot. Inhaled corticosteroids have an anti-inflammatory effect and
278 J.S. Hill and P.J. Davis

result in decreased airway inflammation, secretion, and reactivity


7 2 - 7 4
and may be helpful if used in the perioperative p e r i o d .
Asthmatic patients have been reported to have significant
7 5 7 6
perioperative complications, ranging from as high as 3 0 % ' to
77
as low as 1 . 7 % . The history for the asthmatic child should in-
clude any potential medical factors that can influence asthma, such
as bronchopulmonary dysplasia or prematurity. One should in-
quire as to the nature and frequency of symptoms, as well as the
severity and precipitating factors. T h e nature and severity of the
last episode should be noted. Any previous and current drug
therapy, including type and duration, should be noted. This is par-
ticularly true for the use of steroids.
Precipitating factors for bronchospasm are cold air, viral infec-
tion, nonhumidified anesthetic gases or oxygen, stress, anxiety, in-
51 61 6 2 7 8 - 8 0
haled allergens, and gastroesophageal r e f l u x . ' ' ' If the pa-
tient is having any exacerbation of their asthma or has a potentially
prolonged or complicated surgical procedure, a formal pulmonary
consultation and evaluation with pulmonary function testing is
81 82
usually r e q u i r e d . ' Asthmatic patients with viral infections
should have their surgery postponed. Outpatient surgery can still
be performed on the well-managed asthmatic patient. All patients
should continue to take their medications up until the time of sur-
gery. Children with reactive airway disease undergoing prolonged
procedures or in whom tracheal intubation is expected should also
receive a beta 2 agonist via an inhaler just prior to surgery.
Patients should be adequately prepared preoperatively to mini-
mize their stress. The patient should be premedicated if there is
any anxiety or excessive excitement, as this may cause increased
risk of bronchospasm. Any allergic component to their asthma
should be maximally treated before the procedure. In patients with
gastroesophageal reflux, antireflux medications should be admin-
istered on the morning of surgery. It is advantageous in the asth-
83
matic patient to avoid intubation if p o s s i b l e . Agents that promote
the release of histamine, such as morphine sulfate or atracurium,
should be avoided. Care should be taken that the anesthetic gases
are humidified and warmed, because nonhumidified cool gases can
84
dry the mucosa and produce bronchospasm. The patient's pre-
operative oxygen saturation and physical examination, including
chest auscultation, should be prominently noted.
Intravenous induction is desirable if preoperative venous ac-
cess can be achieved without undue stress. Propofol is probably
the best intravenous agent because of its rapid onset and increased
85
suppression of airway reflexes. It is important to give an adequate
Anesthesia for Pediatric Otolaryngic Patient 279

dose and ensure the child is well anesthetized before intubation.


For those patients in whom venous access is difficult, inhaled in-
duction of anesthesia can be safely done. Halothane or sevoflurane,
along with nitrous oxide, are the common inhaled anesthetic agents
used in children. Sevoflurane has been found to cause less cough-
ing and airway irritation during induction. Both drugs have bron-
chodilating properties. Topical lidocaine helps prepare the airway
before manipulation with a bronchoscope or endotracheal tube.
The lidocaine is administered as 2 mg/kg of lidocaine topically as
a spray. Albuterol, 5 |xg/kg can be added to the lidocaine laryngo-
tracheal anesthesia. Laryngeal mask airway may be a good alterna-
65
tive to endotracheal intubation in some patients. For the mainte-
nance of anesthesia, the use of the volatile agents halothane and
sevoflurane is preferable to the use of anesthesia with opioids and
nitrous oxide because of the bronchodilator effects of the volatile
86
agents.
Intraoperatively, wheezing has multiple causes. The most com-
mon is light anesthesia. Endotracheal tube irritation, bronchial in-
tubation, airway foreign body, secretions, pulmonary edema, pul-
monary emboli, or aspiration are other causes of intraoperative
wheezing. Each possibility must be investigated and ruled out. De-
pending on the cause, various intraoperative measures can be un-
dertaken to treat the bronchospasm, including deepening of the an-
esthesia or administering neuromuscular paralysis and intravenous
lidocaine. Medications for treatment include administering an in-
haled beta 2 agonist via mixing chamber or intravenous steroids.
Steroids may also be given intraoperatively via mixing chamber as
an aerosol. Any extubation technique can be planned, as asthmatic
patients generally do well with either deep or awake extubation if
the intraoperative course has been free of bronchospasm.

Cystic Fibrosis
Cystic fibrosis is the most common, fatal, congenital disease of
whites. There is a 4 . 5 % incidence of the heterozygous genotype in
the general population. This gives a gene frequency of 1 in 25
whites. It has been reported to occur in 1 of 3 , 0 0 0 live births and
8 7 8 8
is inherited as an autosomal recessive g e n e . ' The basic defect
in cystic fibrosis is abnormal epithelial chloride and sodium trans-
port resulting in an increase of electrolyte content of secretions,
89, 90
with altered transluminal potential difference. This results in
a dehydration and a thickening of mucous and in abnormal muco-
91
ciliary c l e a r a n c e . The patients are chronically colonized with
Haemophilus influenzae and Staphylococcus aureus and eventu-
280 J.S. Hill and P.J. Davis

ally by a mucoid variant of Pseudomonas. They have a chronic in-


fection of the tracheobronchial tree that results in bronchiolitis
with airway hyperresponsiveness, bronchiectasis, lobar segmental
atelectasis, occasional pneumothorax with eventual cor pulmonale
92
and respiratory failure. These changes result in distal airway ob-
struction and hyperinflation with subsequent ventilation perfusion
inequalities. On pulmonary function testing the forced expiratory
flow ( F E F ) _ , F E F , and F E F are all decreased. There is an in-
2 5 7 5 5 0 7 5

crease in the residual volume to total lung capacity ratio. Airway


hyperreactivity is frequently present; responses to bronchodilators
often are inconsistent, even within the same patient who may have
previously responded. Occasionally, bronchodilators can even
worsen ventilation secondary to relaxation of bronchial smooth
9 3 , 9 4
muscle and subsequent increased collapse of the a i r w a y .
It is important to realize that there are wide spectrums of dis-
ease severity and patterns of organ involvement. There are very few
studies concerning anesthesia and cystic fibrosis. In 1 9 6 4 , Salani-
tre reviewed 133 anesthetics in 93 patients with cystic fibrosis dur-
ing the previous 18 years. The perioperative mortality in the series
95
was 2 7 % with a 4 2 % incidence of pulmonary c o m p l i c a t i o n s . Do-
ershuk et al. reviewed 144 anesthetics during the previous 11 years
96
and showed a 4% perioperative mortality r a t e . In 1 9 8 5 , Lamberty
and Rubin examined 126 anesthetics and showed a 9% complica-
87
tion rate with no deaths in the perioperative p e r i o d .
Both the family and the patient are usually extremely knowl-
edgeable about their disease. It is better not to undermine their trust
in you by appearing poorly prepared or having inadequate knowl-
edge of this disorder. Often death is pre-eminent in their mind be-
cause of the known mortality of this disease. They are often highly
anxious patients and preoperative sedation with a benzodiazapine
may be required. However, because the patients have little pulmo-
nary reserve, they should be carefully monitored while being se-
dated.
Pulmonary function is usually markedly abnormal with ob-
struction and air trapping resulting in ventilation/perfusion (VQJ
inequalities, hypoxemia, and hypercapnia. They usually have in-
creased pulmonary secretions. Pulmonary assessment is often dif-
ficult at bedside, and clinical chest signs can be misleading as to
the degree of pulmonary dysfunction. Chest radiograph in these pa-
tients is often helpful for evaluation of infection and to give a base-
97
line lung status. It is extremely important to exclude an active
infection. Chest symptoms and fever may be helpful but are often
absent in these patients. The gold standard for documentation of a
Anesthesia for Pediatric Otolaryngic Patient 281

new infection is a change in the flora of the patient's sputum cul-


tures. If possible, any active infection should be treated before ad-
98
ministration of an anesthetic. Care should be taken in the preop-
erative evaluation to search for nasal polyposis. Increased nasal se-
cretions and airway secretions can irritate the larynx and result in
laryngospasm. Some investigators have used C-reactive protein to
99
look for acute exacerbation of cystic fibrosis.
Probably the most important testing for these patients is pre-
operative pulmonary function testing. The best predictive value is
the forced expiratory volume in 1 second ( F E V J . Values of 3 0 % or
less of predicted are associated with a poor risk for general anes-
100
t h e s i a . Arterial blood gases are also good indicators of disease
severity; however, it is often not possible to obtain an arterial blood
gas preoperatively in these patients. An increased partial pressure
of carbon dioxide (PC0 ) indicates severe pulmonary disease. A
2

low arterial partial pressure of oxygen ( P 0 ) is frequently associ-


2

ated with cor pulmonale. Cor pulmonale should be evaluated with


echocardiogram and electrocardiogram. Cardiac function should be
fully evaluated before administering anesthesia. Electrocardiogram
may show a right axis deviation, but this is unreliable. Clinical ex-
amination and echocardiography are more reliable indicators of cor
101
pulmonale. Preoperative preparations should include vigorous
physiotherapy until immediately before induction. It should in-
clude judicious use of antibiotics to treat any existing infection. It
should be noted that the most effective treatment for cor pulmo-
102
nale is improved pulmonary f u n c t i o n .
During the preoperative evaluation, the anesthesiologist and
surgeon should be aware that cystic fibrosis is a multisystem dis-
ease, and the patient may have gastrointestinal and hepatobiliary
abnormalities resulting in decreased serum albumin. This can re-
sult in decreased drug protein binding with an increase in drug po-
tency. Electrolyte abnormalities can occur in patients with cystic
fibrosis as a result of diuretic use or syndrome of inappropriate an-
1 0 3 , 1 0 4
tidiuretic h o r m o n e . Diabetes and glucose intolerance with
subsequent hyperglycemia and acidosis are common. It has been
shown that some patients with cystic fibrosis can develop amyloid-
105
osis with subsequent renal i m p a i r m e n t . Other causes of renal
damage in these patients may be the deposition of immune com-
100
p l e x e s . They may also have coagulopathies related to vitamin K
malabsorption and liver failure.
Premedication should be used judiciously. If it is used, benzo-
87
diazapines are the drug of c h o i c e . The use of atropine in these
patients is debated because of questionable drying effects on mu-
282 J.S. Hill and P.J. Davis

cous that may result in decreased sputum clearance. The published


9 5 , 1 0 7
series does not support t h i s . However, the risk of hypoxemic
bradycardia induction is very real, so a compromise is usually to
87
give atropine at the time of induction.
Intravenous inductions of anesthesia are preferred because of
the prolonged inductions associated with inhaled anesthesia in pa-
tients with ventilation-perfusion abnormalities. Cystic fibrosis pa-
tients rely on a hypoxic drive to breathe, so assisted ventilation is
often required. Propofol and thiopental are the most common in-
duction agents. Ketamine should be avoided in cystic fibrosis pa-
tients because it increases secretions and predisposes to laryngo-
87
s p a s m . If venous access cannot be obtained before induction, in-
halation anesthesia may be the only choice for induction. However,
the anesthesiologist should be prepared for a prolonged induction
with potential complications of coughing, bronchospasm, and la-
ryngospasm. Tracheal intubation is required for all but the short-
est procedures. Tracheal intubation can also allow for intraopera-
tive pulmonary lavage.
Nasal intubation should be avoided if nasal polyposis is
present because of the risk of introducing a polyp as a foreign body
into the airway. Nasal polyposis in these patients increases until
the patients reach puberty, but usually in the late teens the inci-
1 0 8 - 1 1 0
dence d e c l i n e s . Intraoperatively, these patients require fre-
quent suctioning and monitoring of chest movement. Airway pres-
sures must be closely monitored and humidification of oxygen and
gases is required. Nitrous oxide is probably a poor choice for these
patients because of the increased risk of pneumothorax. It is better
to use an air oxygen mixture. Halothane, sevoflurane, and isoflur-
ane are the commonly administered inhaled anesthetic agents.
Nondepolarizing neuromuscular blocking agents are frequently
used. It must be remembered that aminoglycosides, which are fre-
quently administered to these patients, can prolong the action of
111
nondepolarizing neuromuscular b l o c k e r s .

CARDIOVASCULAR DISORDERS
Murmurs
Heart murmurs are the findings that necessitate a cardiac consul-
tation most frequently. At least 5 0 % of children will demonstrate a
murmur at some point in their childhood. The vast majority of these
murmurs are "innocent" and not associated with subsequent car-
112
diovascular d i s e a s e . Innocent murmurs are simply flow mur-
113
murs arising from normal cardiovascular f l o w . Congenital heart
Anesthesia for Pediatric Otolaryngic Patient 283
1 1 4 - 1 1 6
disease is present in less than 0 . 0 8 % . A history of cyanosis,
decreased exercise tolerance, poor weight gain, diaphoresis, abnor-
mal peripheral pulses, or the presence of a precordial heave are sug-
gestive of congenital heart disease. If the child is normally growing,
112
it is less likely that it is a physiologically significant m u r m u r . In-
nocent murmurs tend to decline with age because the normal flow
vibrations become more difficult to hear as the chest wall becomes
thicker.

Congenital Heart Disease


Congenital heart disease in children can be challenging for both
the surgeon and anesthesiologist. Preoperative evaluation may in-
clude hematocrit, electrocardiogram, and chest radiograph. A base-
line oxygen saturation should be obtained. Cardiology consult
should be obtained if the child has an undefined cardiac disease
or a known cardiac lesion with worsening symptoms. Patients who
have either an unrepaired cardiac anomaly or have undergone pal-
liative procedures require the expertise of a pediatric anesthesiolo-
gist experienced in anesthetic management of the cardiac patient.
Anesthetic agents affect cardiac preload, afterload, contractil-
ity, and conduction. They also affect the pulmonary vasculature
and influence ventilation perfusion mismatching. Both inhalation
and intravenous anesthetic agents can have significant effects in
children with congenital heart disease. The presence of these un-
derlying heart defects magnify greatly the risk of anesthesia. It is
imperative that adequate preoperative planning is performed for
these children.
In patients with worsening signs and symptoms of their car-
diac disease, cardiology consultation and possible cardiac catheter-
ization may be required to fully evaluate or re-evaluate the under-
lying disorder. It is important that the anesthesiologist and surgeon
have an adequate understanding of the patient's cardiovascular
physiology. Patients with right-to-left shunts who are cyanotic can-
not withstand long NPO times. Adequate hydration is essential for
these patients to avoid sludging, thrombosis, and shunt occlusion.
In addition, the inhaled induction of anesthesia is prolonged, and
reversing the cardiac depressant effects of the inhaled anesthetic
agents is difficult. Conversely, for those patients with left-to-right
shunts, prolonged NPO periods are well tolerated and induction
times with inhaled anesthetic agents are unaffected by the shunt.
It is also important for the anesthesiologist to know the child's
room air saturation ( P S 0 ) . This is especially true for patients with
2

single ventricle physiology in whom small changes in P S O imply z


284 J.S. Hill and P.J. Davis

significant changes in the pulmonary-to-systemic blood flow ratios.


Care must be taken to avoid any intravenous bubbles in patients
with intracardiac communications.

Subacute Bacterial Endocarditis


Prophylaxis for bacterial endocarditis should be according to the
117
regimen recommended by the American Heart A s s o c i a t i o n . Sub-
acute bacterial endocarditis prophylaxis (SBE) is indicated for any
procedure in which the child is at risk for transient bacteremia. Ex-
amples of such procedures in otolaryngology are sinus or airway
manipulation and any procedure involving aerodigestive tract or
chronic ear surgery. Any procedure in which the surgical site is
contaminated, such as a neck abscess, should receive prophylaxis
as well. Any patient who has undergone palliative or corrective car-
diac procedures requires prophylaxis. One exception is children
who have had ligation of a patent ductus arteriosis or who had pri-
mary closure of a secundum atrial septal defect without the use of
a prosthetic patch. They require prophylaxis only in the 6 months
immediately after surgery. It is important to give the prophylactic
antibiotic prior to the beginning of the procedure. Table 4 shows
the current recommendations from the American Heart Association
for prophylaxis. Prophylaxis is required in patients even if their
heart lesions are not hemodynamically significant. Any patient
with a prosthetic device or foreign body implant should receive
appropriate prophylaxis.

HEMATOLOGIC/ONCOLOGIC/IMMUNOLOGIC DISORDERS
The most important pieces of information in the preoperative
evaluation for bleeding disorders are the past history and the fam-
ily history. These items will help to direct further testing. Unfor-
tunately, pediatric patients often have not had their clotting cas-
cade challenged in a way that would demonstrate a subtle bleed-
ing disorder. Because of significant family histories and a high
incidence of spontaneous bleeding, the majority of patients with
classic hemophilia (hemophilia A) or Christmas disease (hemo-
philia B) are known to have disease at the time of presentation.
However, patients with von Willebrand disease (vWd) and other
mild hereditary coagulopathies are often undiagnosed at presenta-
tion for routine otolaryngic procedures.
von Willebrand disease encompasses a family of molecular de-
fects with multiple subtypes affecting 0 . 8 % to 2% of the popula-
118
t i o n . Clinical problems arise from either a quantitative or quali-
tative defect in von Willebrand factor. This results in a hybrid he-
TABLE 4.
Regimen for Dental, Oral, Upper Respiratory Tract, or Esophageal
Procedures—All Patients

INITIAL DOSE: 1 hour before procedure ORALLY, or 30 minutes before


procedure intramuscularly (IM) or intravenously (IV).
A FOLLOW-UP DOSE IS NO LONGER RECOMMENDED.
1. Standard dosages—Not allergic to penicillin

Route < 40 kg (88 lbs) > 40 kg (88 lbs)


Amoxicillin Oral 50 mg/kg 2 gm
Ampicillin IV or IM 50 mg/kg 2 gm

2. Penicillin allergy or patients on daily rheumatic fever prophylaxis;


or patients receiving penicillin/amoxicillin:
A FOLLOW-UP DOSE IS NO LONGER RECOMMENDED:

Route < 30 kg (66 lbs) > 30 kg (66 lbs)


Clindamycin Oral or IV 20 mg/kg 6 0 0 mg
Regimen for Gastrointestinal/Genitourinary Procedures (excluding
esophageal)

1. High-risk patients (prosthetic valve, previous subacute bacterial


endocarditis, complex cyanotic heart disease, systemic to pulmonary
shunts or conduits)
A. Standard
Initial dose (IM or IV only): Ampicillin 50 mg/kg (maximum 2 g)
plus gentamicin 1.5 mg/kg (maximum 120 mg)
Follow-up dose (6 hrs later): Amoxicillin 25 mg/kg (maximum
1 g) orally or ampicillin 25 mg/kg (maximum 1 g)
B. Patients with penicillin allergy
Initial Dose: Vancomycin 20 mg/kg (maximum 1 g) IV during 1-2
hours plus gentamicin 1.5 mg/kg (maximum 20 mg)
Complete infusion within 30 minutes of starting the procedure
2. All other patients
A. Standard (not allergic to penicillin): Follow recommendations
above for dental procedures
B. Allergic to penicillin: Vancomycin 20 mg/kg (maximum 1 g) in
1-2 hours, complete infusion within 30 minutes of starting the
procedure.
Abbreviations: kg, kilogram; g, grams; mg, milligram; 76s, pounds
Adapted from Dajani AJ, et al: Prevention of bacterial endocarditis. Recommendations by
the American Heart Association. JAMA 277:1794-1801, 1997. Copyright 1997, American
Medical Association. Used by permission.
286 J.S. Hill and P.J. Davis

mostatic defect of abnormal platelet aggregation and decreased


levels of factor VIII coagulant activity (VIII:C), leading to a
prolonged bleeding time and activated partial thromboplastin time
119
(aPTT), respectively. Evaluation of the child with a suspected
bleeding disorder includes a preoperative history and physical
with emphasis on any past bleeding episodes and the family his-
tory of bleeding. Laboratory screening should include hemoglobin,
hematocrit, prothrombin time (PT), and aPTT. Bleeding time is only
obtained if the patient's past medical history, family history, or
laboratory results warrant it. Patients with abnormalities undergo
further coagulation testing to determine the presence of a heredi-
tary or acquired coagulopathy. Patients with vWd have von Will-
ebrand (vW) antigen multimer electrophoresis and ristocetin plate-
let stimulation performed to further exclude vWd type IIB and
platelet-type vWd. If this form of vWd is excluded, a DDAVP chal-
1 2 9 , 1 2 1
lenge test is p e r f o r m e d . Patients are administered 0.3 u.g/kg
of DDAVP in 50 mL of normal saline intravenously; bleeding time
and coagulation studies are performed both before and 30 minutes
after the DDAVP infusion. If an acceptable response to DDAVP chal-
lenge is demonstrated, the patient is administered DDAVP (0.3 u,g/
kg) 30 to 40 minutes before surgery. The use of DDAVP is not with-
out complications. Because of its antidiuretic effect, significant hy-
1 2 2 - 1 2 5
ponatremia and seizure activity can o c c u r . Not all patients
with vWd are responsive to DDAVP. It is typically useful in patients
with types I and IIA disease. When DDAVP is not indicated, or
when it is not effective in controlling postoperative bleeding,
plasma-derived factor VIII concentrate (Humate-P, Armour Pharma-
ceutical) can be used. Humate-P is a pasteurized, intermediate-
purity factor VIII concentrate that contains not only high levels of
factor VIII but also a full range of hemostatically active vWf mul-
timers. Although used widely for patients with vWd in the past,
cryoprecipitate is not recommended because of the risk of trans-
mitting viral agents. Studies have reported the safety of single doses
of DDAVP used in an outpatient setting without serum sodium
1 2 2 - 1 2 5
monitoring. However, even single doses may lead to signifi-
cant hyponatremia if accompanied by aggressive intravenous hy-
dration and poor oral intake. Thus, patients in the postoperative
period should be carefully monitored with serum sodium determi-
nations.

Sickle Cell Disease


Every anesthetic preoperative evaluation should include questions
about hematologic disorders in both the child and the child's fam-
Anesthesia for Pediatric Otolaryngic Patient 287

ily. This is particularly important for children at risk for hemoglo-


binopathies. Sickle cell disease (Hb S S ) is an autosomal recessive
hemoglobinopathy derived from a single nucleotide mutation on
chromosome 11 in the black population. This results in the substi-
tution of valine for glutamate in the hemoglobin molecule. This
substitution disrupts the normal intramolecular interactions within
the hemoglobin molecule. Under normal conditions, the Hb S mol-
ecule is similar to the normal hemoglobin molecule (Hb A). When
the hemoglobin S is subjected to conditions of hypoxia, dehydra-
tion, hypothermia, and acidosis, abnormal polymerization of the
hemoglobin S occurs and the red blood cells sickle. This results in
anemia and vaso-occlusive events. Although the parents of these
patients are usually aware of the many problems and risks their
child's sickle cell disease may pose, they may not be aware of the
potential complications that can be precipitated by general anes-
thesia. Therefore, it is the responsibility of the surgeon and anes-
thesiologist to elicit the history of sickle cell disease and plan the
anesthetic and procedure to minimize risk to the patient. Other he-
moglobinopathies that can result in anesthetic difficulties include
hemoglobin C (Hb C) disease and sickle-beta thalassemia (Hb S/T
thai). These disorders may need to be managed similarly as are
those in patients with sickle cell disease.
Sickle cell disease has been associated with increased inci-
dence of perioperative complications in patients undergoing vari-
ous procedures. Otolaryngic procedures are usually classified as
low risk for patients with sickle cell disease. However, some air-
way cases may pose particular risk because of the potential for dif-
ficulties with oxygenation associated with these procedures. Thus,
in the past, aggressive preoperative transfusion regimens were used
to minimize these risks. At present there is controversy over the
optimal preoperative management of the pediatric patient with
sickle cell disease. The 1 9 9 4 cooperative study of sickle cell dis-
ease noted that 7% of all deaths in patients with sickle cell dis-
126
ease were related to surgery. In a recent study by Vichinsky and
others, these investigators noted a perioperative mortality rate of
1 2 7
1.1%. In this cooperative study, where patients were random-
ized to either an aggressive preoperative transfusion group (hemo-
globin S level less than 3 0 % ) or a conservative regimen designed
to increase the hemoglobin level to 10 g/dL, Vichinsky and others
noted no difference between the two groups with respect to perio-
127
perative c o m p l i c a t i o n s . However, the conservative group had
significantly fewer transfusion-related complications than the pa-
tients in the aggressive group.
288 J.S. Hill and P.J. Davis

Sickle cell trait (heterozygous form) is generally a benign con-


dition and usually does not involve anemia, although hyposthe-
nuria is frequent and splenic infarction and sequestration of blood
128
have been reported in people at high a l t i t u d e s .
The anesthetic management of patients with sickle cell trait is
somewhat controversial. Because it is qualitatively similar to sickle
cell disease, some believe that the anesthetic management should
129
be s i m i l a r . Although numerous series and case reports cite an-
esthetic morbidity in patients with sickle cell trait, most studies or
130-134
reports have significant design flaws. In a matched-pair
study of patients with sickle cell trait and normal HbA, Atlas noted
no difference with respect to length of hospitalization or periop-
135
erative c o m p l i c a t i o n s .
For patients with sickle cell trait, adequate measures to avoid
hypoxia, hypotension, and dehydration should be undertaken so
that any reasonable anesthetic technique is acceptable. Periopera-
tive blood transfusion is unwarranted in these patients.

Oncologic Diseases
Children with oncologic diseases frequently present to the otolar-
yngologic surgeon for surgical resection of tumor or tissue biopsy
for diagnosis or management of opportunistic infections of the head
and neck. Often, the treatment of their malignant disease will di-
rectly affect their anesthetic and surgical management.
In preparation for a procedure, a summary of their disease pro-
cess and all chemotherapeutic agents they have received should
be obtained before administration of any anesthetic. Historical
questions should include inquiries about dyspnea, orthopnea,
cough, fainting, cyanosis, or other physical signs of compromise.
Children who have a mass in the mediastinum, especially of the
anterior mediastinum, may have special risk during the induction
1 3 6 , 1 3 7
of a n e s t h e s i a . Care should be taken to note any anesthetics
that are known to produce cardiac or pulmonary toxicity. Areas of
radiation therapy should be duly noted, especially when these in-
volve areas of the airway or thoracic cavity. A chest radiograph and
complete blood count with appropriate white cell evaluation
should be obtained before any procedure is begun. Chest x-rays are
particularly important in children who may have thoracic involve-
10
ment with their malignancy.
Various chemotherapeutic agents such as cisplatinum, metho-
trexate, and cyclophosphamide have documented nephrotoxicity.
These patients may also receive antimicrobials such as aminogly-
cosides and amphotericin that may further damage their kidneys.
Anesthesia for Pediatric Otolaryngic Patient 289

Preoperative electrolytes, blood urea nitrogen, and creatinine are


required in these patients. Correction of any electrolyte abnormali-
ties and possible preoperative or postoperative hemodialysis may
be required. Hypercalcemia may be present with osseous tumors
or with bony erosion by other malignancies. The dosage of drugs
must be appropriately altered, depending on the patient's renal
clearance. This is especially true with certain muscle relaxants. In
patients with known liver dysfunction from either their malig-
nancy or chemotherapeutic agents, alterations of the anesthetic
regimen to minimize the risk of further hepatocellular damage may
138
be r e q u i r e d .
Children who have received bleomycin or mitomycin C require
a thorough evaluation of their pulmonary function, including pul-
monary function testing. These may reveal a restrictive pattern or
139
diffusion abnormality. Chest x-ray is often not helpful unless
there is suspicion for an acute pneumonic process. Exposure to in-
creased oxygen concentration increases the risk of pulmonary tox-
140
icity after b l e o m y c i n . These patients should be monitored in the
immediate preoperative period with a pulse oximeter. Limiting
perioperative oxygen concentration in these patients to 2 5 % to
2 8 % has been recommended, unless one is unable to maintain ad-
141
equate or arterial oxygenation.
Cardiac evaluation is especially important in patients who
have received anthracycline, Adriamycin, or cyclophosphamide, or
in those who have a known cardiomyopathy. Patients with a his-
tory of mediastinal irradiation are at increased risk for a restrictive
cardiomyopathy. Echocardiogram will assist in determining the
1 4 2 , 1 4 3
myocardial reserve in these p a t i e n t s . Beta-adrenergic agents
may be ineffective in increasing cardiac output in these patients,
144
secondary to a prolonged increase in sympathetic hyperactivity.
Agents such as amrinone may be helpful. Anesthetic agents that
are negative inotropic agents (e.g., halothane, isoflurane, ketamine)
should be avoided or used in very low concentrations. The
patient's fluid status should be optimized prior to induction of an-
esthesia.
Children with malignancies may have decreased liver function
and abnormal coagulation times. They also may be thrombocyto-
138
penic or have platelet dysfunction. Hemoglobin determination
is also frequently indicated in patients who have had chemo-
therapy radiation or bone marrow infiltration or hemorrhage.
Thrombocytopenia may arise secondary to marrow infiltration or
suppression. Coagulation defects may result from certain chemo-
therapeutic agents such as actinomycin D and the anthracyclines.
290 J.S. Hill and P.J. Davis

Patients who are receiving chemotherapeutic agents are immune


suppressed and consequently are at risk for a disseminated intra-
vascular coagulopathy associated with septicemia or end-stage dis-
ease. Patients with acute promyelocytic leukemia, hepatic tumors,
malnutrition secondary to their tumors, or vitamin K deficiencies
all may have increased risks for bleeding. For any major surgical
procedure, the platelet count should be above 5 0 , 0 0 0 per microli-
138 1 4 5
ter. -
Adequate intravenous access may be necessary for fluid resus-
citation or blood product transfusion. There is significant risk as-
sociated with blood transfusion in these patients. Often they have
had prior transfusions and reactions are common. These trans-
fusion reactions are often subclinical but can be lethal. There is
also a real risk of the transmission of HIV, hepatitis, and cytomeg-
alovirus disease. Graft-versus-host disease is another potential
complication, especially for allogenic bone marrow transplant pa-
138
t i e n t s . With all these problems in mind, it is in the patient's best
interest to minimize transfusion when possible. Any cellular blood
products should be irradiated to decrease the risk of graft-versus-
host disease and should be leukocyte free to minimize the risk of
1 4 6 - 1 5 1
other c o m p l i c a t i o n s . Patients with a history of transfusion
reaction should be premedicated with steroids and Benadryl. They
also may receive premedication with acetaminophen. If the patient
has a severe allergic reaction to a transfusion, then epinephrine
may be required. Patients with leukocytosis and acute leukemia are
at risk for complications similar to those of sickle cell patients, in-
cluding sludging and hemorrhage, with increased risk of pulmo-
nary or cerebral vascular events. Before surgery, the leukemic pa-
tient's white blood cell count should be lowered to below 1 0 0 , 0 0 0
per microliter via leukophoresis or by a partial exchange transfu-
152 1 5 3
sion. '
The patient with a malignancy also may be septic. The septic
patient will require fluid resuscitation prior to induction. These
children will deteriorate rapidly if they are not fluid resuscitated
adequately. Because inhaled anesthetic agents are myocardial de-
pressants, they should be administered judiciously. Both chrono-
tropic and inotropic support may be required to support the admin-
istration of anesthetic agents. In hemodynamically compromised
individuals, intravenous agents are preferable. Propofol, along with
opioids, is easily titrated and allows for rapid induction and emer-
1 5 4 1 5 5
gence with minimal hemodynamic c o n s e q u e n c e . ' However,
each patient's anesthetic management must be individualized.
Anesthesia for Pediatric Otolaryngic Patient 291

Transplanted Patients
There has been a significant increase in the number of organ trans-
plantation programs in the country. Survival statistics have im-
proved significantly with the advent of improved immunosuppres-
sive regimens. These increased survival rates have resulted in a
growing number of patients presenting for surgical procedures un-
related to their transplant, as well as those related to transplanta-
tion. Chronic sinusitis, especially with fungal agents, neck ab-
scesses, and ear disease are the most frequent otolaryngologic pre-
sentations. It is important that the anesthesiologist understand the
implications of transplantation in these children and how it will
affect the administration of anesthesia. Often the transplantation
will directly impact the efficacy of a drug. One example is the lack
of effect that atropine has on the denervated transplanted heart.
Other aspects of general anesthesia are the same for the trans-
planted child as in the normal child; however, there are specific
problems unique to the transplanted patient. The old chart must
be available for review, as these patients have usually had multiple
admissions as well as anesthetics. Often they have other associated
congenital anomalies. These are very complex patients, and it is a
difficult task to balance the physiologic, psychological, and func-
tional needs of the child during the perioperative period. The main
risks in a transplanted patient are potential for infection and rejec-
tion, as well as the side effects of chronic immunosuppressive
158
therapy.
Immunosuppression protocols vary widely among hospitals, as
well as among types of transplant patients. The patient may
receive a myriad of drugs including azathioprine, cyclosporine A,
antilymphocyte globulin and monoclonal antibodies, FK-506, and
corticosteroids. These immunosuppressive drugs can influence
the type of anesthesia administered, as well as interact with
various anesthetic medications. Examples of this include the
prolongation of neuromuscular blockade with atracurium and
1 5 7 1 5 8
vecuronium with c y c l o s p o r i n e . ' In addition, cyclosporine
can be hepatotoxic and nephrotoxic. Drugs that may have addi-
tive renal toxic effects, such as nonsteroidal anti-inflammatory
medications, are contraindicated. In addition, drugs such as
morphine which are renally excreted may have to be modified in
their administration. Steroids are often given in high doses and
can result in a cushingoid appearance, electrolyte and glucose
abnormalities, hypertension, and diabetes. Chronic immunosup-
pression with steroids places the patient at an increased risk
292 J.S. Hill and P.J. Davis

of lymphoproliferative disease and malignancies such as lym-


156
phoma. Children who have been receiving prolonged steroid
immunosuppression require a steroid replacement regimen as
previously described.
The other significant risk involved with transplant patients is
the concern of bacterial, viral, fungal, or protozoan infection. Cy-
tomegalovirus infection can be lethal in these cases. It is impera-
tive that a sterile technique be used with any invasive procedures,
and prophylactic antibiotics should be given before the procedure.
Any blood product used should be screened for cytomegalovirus.
Blood products should be white-cell filtered to prevent transmis-
sion of cytomegalovirus in white blood cells. Blood to be given to
transplant patients should also be irradiated to destroy any T cells,
156
as these may cause graft-versus-host d i s e a s e . Because these pa-
tients have frequent procedures, a thorough preoperative assess-
ment with an emphasis on their psychological well-being cannot
be overstated.

NEUROLOGIC

Down Syndrome
Down syndrome is a relatively common disorder with an incidence
159
of approximately one in 800 b i r t h s . It is the most common con-
genital chromosomal anomaly. Often these patients have multiple
disorders and anomalies related to their Down syndrome. In the
past, their life expectancy was short, with very few patients living
until adulthood. Now these patients enjoy a much greater life ex-
pectancy. Yet they often have multiple congenital anomalies that
160
may have great implications on the administration of a n e s t h e t i c .
It is generally believed that these patients have a higher risk than
1 6 0 , 1 6 1
otherwise healthy p a t i e n t s . Kobel reviewed 100 patients
1 6 2
with trisomy 2 1 . His findings showed a very low incidence of
complications when optimal anesthetic care was given.
Preoperative evaluation should include the usual history and
physical examination, as well as laboratory studies. In addition,
there are multiple systemic areas that need special attention.
Twenty-three percent of children with Down syndrome have been
shown to have respiratory infection in the immediate preoperative
period. Individuals with Down syndrome tend to have immune de-
163
ficiency. Although there is an increase in susceptibility to all in-
fections, they are particularly predisposed to upper respiratory in-
164
f e c t i o n s and hepatitis B infection. Patients with Down syndrome
Anesthesia for Pediatric Otolaryngic Patient 293

also appear to have an increased incidence of leukemia and poly-


165
cythemia.
Upper airway obstruction and obstructive sleep apnea are
1 6 1 1 8 2 1 6 6
extremely common in patients with Down s y n d r o m e .
The airway obstruction is secondary to large tongue and relatively
crowded midfacial structures. They have a high-arched narrow pal-
ate and micrognathia. Further compromising their already small
airway, these patients have a high incidence of tonsil and adenoid
hypertrophy, coupled with relative pharyngeal hypotonia. Patients
with Down syndrome have short, broad, thick necks, making air-
way manipulation and maintaining a patent airway difficult. Chil-
dren with Down syndrome have been reported to have an increased
incidence of subglottic stenosis and consequently require a smaller
endotracheal tube than predicted for age. However, Down syn-
drome patients are frequently small for their age and this factor also
1 6 2 , 1 6 7
may account for the smaller endotracheal tube s i z e . Patients
with Down syndrome also may have poor ventilatory drive mecha-
nisms. Consequently, spontaneous ventilation during anesthesia
168
may result in hypercapnia and h y p o x e m i a . Thirty percent to
4 0 % of children with Down syndrome intubated for a prolonged
period have postextubation stridor compared with 2% in children
who do not have Down syndrome.
Down syndrome is frequently associated with cardiac anoma-
lies. Forty to 5 0 % of children with Down syndrome have known
169 171
cardiac a n o m a l i e s . " The most common lesions include ven-
tricular septal defect, atrial ventricular canal defect, atrial septal
defect, and endocardial cushion defect. In addition, patent ductus
arteriosis and mitral valvular stenosis or insufficiency are common.
1 6 2 , 1 7 1
Tetralogy of Fallot is also s e e n . Children with Down syn-
drome may have an unusually high pulmonary vascular resistance
172
and are more prone to early onset pulmonary hypertension.
Gastrointestinal abnormalities also are common. Duodenal
atresia, Hirschsprung's disease, and gastroesophageal reflux are
173 175
commonplace. " Children with Down syndrome have been
176 177
shown to have increased incidence of h y p o t h y r o i d i s m , ' of-
ten with minimal associated signs and symptoms present.
One of the biggest anesthetic concerns in patients with Down
178-180
syndrome is atlantoaxial i n s t a b i l i t y . The reported incidence
1 6 0 1 8 1
varies between 9% and 3 2 % . ' The instability is thought to be
secondary to laxity of the transverse atlantal ligament, which usu-
ally holds the odontoid process in approximation to the arch of the
atlas. With laxity of this ligament, there is predisposition to spinal
cord injury. Because of this relationship, many of these patients
294 J.S. Hill and P.J. Davis

will have had a radiologic examination of the spine. A thorough


symptom history should be taken, including specific questions re-
garding any history of neck pain or torticollis. A thorough neuro-
logic examination should be performed to designate any neurologic
abnormalities including reflexes, clonus, or Babinski's sign. Pa-
tients should be thoroughly evaluated by either their pediatrician
or neurologist before any surgical procedure. There is controversy
as to whether repeat films are needed if there has been an interval
since previously normal films. Care should be taken to minimize
cervical spine manipulation during the procedure. However, a
study of Down syndrome patients showed that the x-ray criteria of
182
instability were not predictive of a tendency to d i s l o c a t i o n . This
was corroborated by Cremers in 1 9 9 3 , who showed that x-ray evi-
dence of instability does not correlate with a risk of a dislocation
183
and cord i n j u r y . Procedures that are particularly prone to caus-
ing atlantoaxial instability are laryngoscopy, internal jugular vein
160
cannulation, and ear p r o c e d u r e s . Because of these various find-
ings, it is still controversial as to whether cervical spine films
should be obtained in all children with Down syndrome before ad-
ministration of anesthesia. If neurologic symptoms or signs are
present, preoperative x-rays, including flexion, extension, and lat-
eral cervical spine films, should be obtained. Orthopedic or neuro-
surgical referrals are mandatory in these cases. If such symptoms
are not present, routine screening is probably not necessary.
Sedation in patients with Down syndrome should be used ju-
diciously because of the predisposition to airway obstruction. Oral
or nasal midazolam is frequently well tolerated as a preanesthetic
medication. The anesthetic induction is often a function of the
child's behavioral disposition. In combative, agitated children, in-
tramuscular inductions with ketamine are frequently performed. In
cooperative patients, inhaled inductions can be safely performed.
Extubation of the patient's trachea should be performed with the
patient as awake as possible. Down syndrome patients have been
noted to have an atropine sensitivity. This includes increased myd-
1 8 4 - 1 8 6
riatic response and increased response of heart r a t e . How-
ever, subsequent studies have not demonstrated this increased car-
1 8 7 1 8 8
diac s e n s i t i v i t y .

MISCELLANEOUS DISORDERS
Malignant Hyperthermia
Malignant hyperthermia (MH) is a rare autosomal-dominant trait
with incomplete penetrance that induces susceptible individuals
Anesthesia for Pediatric Otolaryngic Patient 295

to a hypermetabolic state when they are exposed to anesthetic trig-


gering agents (e.g., halothane, sevoflurane, desflurane, isoflurane,
and succinylcholine). Recently, a mutation in the ryanodine recep-
tor gene on chromosome 19 was linked to malignant hyperthermia
189
s y n d r o m e . When MH-susceptible patients are exposed to trig-
gering agents, there is a rapid accumulation of calcium within stri-
ated muscle myoplasm that results in muscle contracture, rhab-
domyolysis, and intense heat production. Mortality from MH has
1 9 0 - 1 9 2
been reported to range from 1 0 % to 5 0 % . Once an MH cri-
sis is initiated, it is treated with dantrolene, a nonspecific muscle
relaxant, and supportive measures (cardiovascular and respiratory
support as well as aggressive patient cooling). Although susceptible
patients are otherwise in apparent good health, some patients do
have underlying or subclinical myopathies (e.g., Duchenne's mus-
193
cular dystrophy). The in vitro caffeine halothane contraction test
has been widely used to diagnose MH. However, this test is often
neither accurate nor specific. Diagnostic tests that detect mutations
in the ryanodine receptor gene are now available. However, these
194
may not detect all patients at r i s k .
The anesthetic preparation for the possibility of MH reaction
is more important than screening. Any individual known or sus-
pected to have MH syndrome should be fully evaluated, and elec-
tive procedures should be done only in centers with experience in
dealing with these disorders. Outpatient surgery is safe in these pa-
tients as long as postoperative monitoring is continued for at least
193
4 hours. Preoperative evaluation should include an anesthetic
consultation and baseline creatine phosphokinase levels. Most an-
esthesiologists do not pretreat known MH patients with dantrolene.
The administration of anesthesia should be as stress free as pos-
sible. Patients with MH should be premedicated with benzodiaza-
pines and/or opioids. Local regional anesthesia is advisable. One
should avoid phenothiazines because of the possible association
between MH and neurolyptic malignant syndrome. All volatile
agents such as halothane, desflurane, sevoflurane, or depolarizing
relaxants must be avoided. It appears that propofol and thiopental
1 9 5
are safe in patients with M H . Ketamine can be safely adminis-
tered to patients with MH; however, its sympathomimetic effects
(tachycardia and hypertension) may mask MH's hypermetabolic ef-
fects. Nitrous oxide is considered safe, although there has been one
case report of its triggering effects. Because of MH's life-threatening
effects, it is important that patients be educated regarding its po-
tential risk and the interactive effects of volatile anesthetic agents
and depolarizing muscle relaxants.
296 J.S. Hill and P.J. Davis

Human Immunodeficiency Virus


The patient infected with HIV presents some special anesthetic
management problems. The two main issues in the care of
HIV-infected children are the interaction of the disease with the
anesthetic agents and the risk of infection to medical personnel.
Patients who are HIV positive are at increased risk for periopera-
tive infection and multiorgan system involvement (renal, cardiac,
pulmonary, metabolic, neurologic, gastrointestinal, and/or hemato-
logic). Careful history and physical examination with focus on or-
gan system involvement are important in the evaluation of these
patients so that an anesthetic can be administered safely. Standard
precautions, formally called universal precautions, should be used
for all patients undergoing surgical procedures. Standard precau-
tions as defined by the Center for Disease Control refer to a set of
practices designed to prevent the transmission of HIV, hepatitis,
and other blood-borne or body fluid pathogens in the health care
setting. Universal precautions include the use of protective barri-
ers such as gloves, gowns, aprons, masks or protective eyeware, and
hand washing between each patient contact to reduce the health
care worker's and patient's risk to infective materials. In addition,
it is recommended that health care workers take appropriate pre-
196
cautions to prevent injuries by sharp instruments or d e v i c e s .

SUMMARY
The opportunities for operative intervention in treating various
childhood illnesses have grown exponentially in recent years. The
physician involved in the care of the child in the perioperative pe-
riod must not become complacent with the status quo. The anes-
thesiologist and otolaryngic surgeon must accept full responsibil-
ity for planning the safest and best-tolerated anesthetic and proce-
dure possible in every patient.

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