International Journal of Pediatric Otorhinolaryngology (2007) 71, 937—941

www.elsevier.com/locate/ijporl

The use of ketamine or ketamine—midazolam

for adenotonsillectomy
Gülcan Erk *, Dilşen Örnek, Nezihe F. Dönmez, Vildan Taşpınar

Department of Anaesthesiology and Reanimation, Ankara Numune Training and Research

State Hospital, Turkey

Received 29 September 2006; received in revised form 2 March 2007; accepted 3 March 2007

KEYWORDS Summary
Anaesthetic;
Ketamine; Background: Ketamin’s role in clinical anaesthesia is developing as a result of the
Midazolam; evolving concepts of its mechanism of action and the advantages of its alternative
Complications; routes of administration. In this study, we aimed to investigate the frequency and
Emergence reactions; severity of adverse effects, specifically emergence phenomena and vomiting, when
Vomiting ketamine with or without midazolam used as a sole anaesthetic.
Methods: One hundred children, aged between 3 and 10 years, scheduled for
adenotonsillectomy were studied. Fifty ASA physical status I—II patients were admi-
nistered ketamine and atropine intramuscularly (group K, n = 50). The remaining 50
children were given ketamine, atropine and midazolam by as the same route (group
KM, n = 50). Noninvasive hemodynamic and oxygenation variables were monitored.
Operative conditions and recovery profiles such as hallucinations, nightmares, awa-
kening by crying agitation and retching—vomiting were investigated in 1st, 2nd, 15th,
30th and 60th days after the operation.
Results: A significant reduction in emergence reactions was demonstrated especially
in group KM during the early postoperative period ( p < 0.05). Retching—vomiting also
reduced significantly in the group KM during the same time ( p < 0.05).
Conclusion: As a sole anaesthetic ketamine with or without midazolam provided a
calm and safe anaesthesia for paediatric patients in short term procedures. In
addition, it must be noted that, a better postoperative early period was achieved
by ketamine with midazolam.
# 2007 Elsevier Ireland Ltd. All rights reserved.

1. Introduction

Ketamine is an old anaesthetic. It has been used for

* Corresponding author at: Ziya Bey Cad. 2. Sok., Yonca sit. B bl.
D.4, 06520 Balgat, Ankara, Turkey. Tel.: +90 312 287 00 06;
fax: +90 312 427 04 67.
E-mail address: gulcanerk@hotmail.com (G. Erk).
premedication, sedation, induction and mainte-
nance of general anaesthesia since the second part
of the 20th century. It has been used especially for

0165-5876/$ — see front matter # 2007 Elsevier Ireland Ltd. All rights reserved.
doi:10.1016/j.ijporl.2007.03.004
938
trauma victims, patients with hypovolemic and sep-
tic shock, patients with pulmonary disease, and
paediatric patients who have behavioural disorders.
However, its usage as a sole anaesthetic agent was
restricted because of the emergence phenomena
resulted with psychological disorientation, halluci-
nations and nightmares, which are named emer-
gence reactions in the postoperative period [1—3].
Ketamin’s clinical usage has become more wide-
spread with the increased understanding of its
mechanism of action [2]. It has been recommended
for use in a variety of areas including controlling
pain, therapy of asthma, intracranial procedures,
hemorrhagic or septic shocks [4].
Ketamine is often used with or without benzo-
diazepines or opioids for preventing preoperative or
separation anxiety in paediatric patients [5—11].
There are few studies in which ketamine has been
used as the sole anaesthetic [12,13]. Hypersaliva-
tion, induction of sympathetic activity, postopera-
tive nausea vomiting are the classical adverse
effects of ketamine which limits its usage [1—3,14].
As far as the adverse effects of use of ketamine are
concerned; use of pharmaceutics such as benzodia-
zepines, physostigmine, droperidol [15], pentozosin
[16] and dexmetadomidin [17] are recommended.
Among them; midazolam, a commonly used benzo-
diazepine are claimed to be the most effective one
[14,18—21]. It is the aim of this study to show whether
or not midazolam is effective in preventing the
adverse effects of ketamine in paediatric patients.
2. Methods
After ethical committee approval and informed con-
sent we studied 100 ASA I—II patients (3—10 years
old) undergoing adenotonsillectomy under general
anaesthesia. Patients with psychiatric disorders,
congenital or anatomical abnormalities, systemic
diseases (hypertension, increased intracranial pres-
sure, glaucoma) and allergic reactions to ketamine
were excluded. The patients were randomly allo-
cated to two groups. Group K received ketamine
7 mg kg 1—atropine 0.015 mg kg 1. Group KM
received ketamine 7 mg kg 1—atropine 0.015
7 mg kg 1—midazolam 0.1 mg kg 1 intramuscularly.
Following intramuscularly injection, the time period
till the patient became unconscious was recorded
and expressed as induction time. The patients were
taken to the operation room immediately following
their separation from their parents. Non-invasive
blood pressure, heart rate and peripheral oxygen
saturation were monitored throughout the study. In
the operation room while they were breathing 100%
O2 spontaneously with a face mask, an i.v. cannula
G. Erk et al.
was inserted. Ringer lactate solution was infused at
a rate of as determines by the 4:2:1 formula [22].
Intubation of the trachea was facilitated with vecur-
onium 0.01 mg kg 1. Patients were ventilated with
65% N2O/O2 mixture using a pressure controlled
mode to maintain an ETCO2 between 30 and
35 mmHg.
Hypertension and tachycardia were defined as an
>30% increase from the baseline values of blood
pressure and heart rate. In case of additional anaes-
thetic requirement; ketamine 1 mg kg 1 i.v. was
given to patients suffering from hypertension or
tachycardia. Before tracheal extubation neuromus-
cular blockage was reversed by neostigmine
0.02 mg kg 1 and 0.015 mg kg 1g atropine intrave-
nously at the end of the surgery.
Finally, all patients received rectal paracetamol
at the end of the surgery.
Assessment for emergence reactions at early
postoperative period was performed for the first
4 h in a silent and dark room. Assessment of the
severity of emergence reactions was scored as
patient silent, sleepy, reactive for verbal stimuli
(none), crying at intervals (mild), anxious and agi-
tated, delirious at intervals (moderate), screaming
with shrieks and cries, uncooperative (severe) by
blind assessors.
Assessment for delayed emergence reactions was
performed at 1st (face to face), 2nd, 15th and 30th
days (contacted with their parents by phone). Four
levels of reactions were graded. Patients who had
silent and quiet sleep at night (none), who awaked
but did not emphasize their anxieties and fears
(mild), who waked up once or twice nightly, crying
and screaming (moderate), who waked up similarly
but cannot be able to sleep again because of night-
mares (severe). Sixty days after ketamine adminis-
tration we invited the patients with their parents to
the hospital to evaluate the possible potential
adverse effects of ketamine on patients during
these periods such as whether or not they had night-
mares, etc.
Assessment of vomiting was started at extubation
and was performed for the first 4 h in a dark and
silent room and then the patients were evaluated on
the ward if they had retching—vomiting. They were
assessed on a 2-point ordinal scale (1) none, (2)
vomiting or two retching or more events. As children
may find it difficult to describe nausea; no distinc-
tion was made between nausea and retching.
Ondansetron 0.1 mg kg 1 i.v. was given when vomit-
ing and retching occured.
Statistical analysis was performed using the Stu-
dent’s t-test; for age, weight and height and chi-
square test for emergence reactions and vomiting. A
p-value less than 0.05 was considered significant.
The use of ketamine or ketamine—midazolam for adenotonsillectomy 939

3. Results Table 3 Postoperative vomiting data

The demographic data, induction and operation
data are presented in Table 1. There were no sig-
nificant differences between groups with respect to
age, weight, gender, time of induction, duration of
surgery and intraoperative fluids. Duration of induc-
tion was shorter in group KM ( p < 0.05).
We did not observe any episodes of apnea, lar-
yngospasm or oxygen desaturation (<87) during the
induction or after the extubation.
Although there was slight and transient hyperten-
sion or tachycardia, we did not encounter any sig-
nificant increase which needs medical therapy
peroperatively.
The incidence of immediate and delayed emer-
gence reactions between the groups as shown in
Table 2. Nursing staff on a dark—silent room
observed the agitation as none 7.1%, mild 67.9%,
moderate 2.5% in group K. In group KM, immediate
agitation was observed as none 10.7%, mild 85.7%,
moderate 3,6%. Immediate agitation which was
described as moderate was significantly decreased
in group KM ( p < 0.05). There was no severe agita-
tion in either the groups during the first 4 h. There
were no differences in delayed emergence phenom-
ena (which was defined as none, mild or severe)
reported by parents in postoperative 1st, 2nd, 30th
and 60th days. Delayed emergence phenomena
Group K Group KM
(n = 50) (n = 50)
Early period (0—4 h) 67.9% * 32.1%
Delayed period (4—24 h) 17.9% 42.9% *
*
p < 0.05.
which was defined as moderate was significantly
decreased on the 15th postoperative day in group
KM.
The incidence of retching—vomiting within the
first 4 h and 4—24 h after surgery were summarized
in Table 3. Group K had statistically significant
increased incidence of retching—vomiting and the
number of needing antiemetic rescue within the
first 4 h after surgery ( p < 0.05). During the 4—
24 h follow-up period group KM had a significantly
increased incidence of retching—vomiting and the
need for antiemetic rescue ( p < 0.05).
4. Discussion
Within 5 min following intramuscularly injection of
ketamine; completing of induction or loss of con-
scious was expected [23]. However; the induction
time lasted long in our study. It was 6.8  1.9 min for
group K and 5.6  1.6 min for group KM. It should be

Table 1 Demographic data and times to induction—operation

Group K (n = 50) Group KM (n = 50) P değerleri
Average age (years) 6.3  2.1 6.1  1.7 0.7
Average weight (kg) 27  13 26  17 0.6
Sex (M/F) 32/18 28/22
Mean time of induction (min) 6.8  1.9 5.6  1.6 0.02 *
Mean duration of operation (min) 22  12 23  18 0.67
Intraoperative fluids (ml) 150  25 145  68 0.69
*
p < 0.05, mean  S.D.

Table 2 Postoperative emergence reaction data

Group K (n = 50) Group KM (n = 50)
None Mild Moderate Severe None Mild Moderate Severe
(%) (%) (%) (%) (%) (%) (%) (%)
Early emergence reaction 7.1 67.9 25 — 10.7 85.7 3.6 * —

Delayed emergence reaction

Postoperative 1st day — 57.1 35.7 7.1 3.6 64.3 32.1 —
Postoperative 2nd day 10 71.4 17.9 — 75 * 3.6 21.4 —
Postoperative 15th day 50 10.7 39.3 — 39.3 57.1 3.6 * —
Postoperative 30th day 35.5 62.5 — — 39.3 60.7 — —
Postoperative 60th day 79.5 20.5 — — 83.7 16.3 — —
*
p < 0.05.
940
emphasized that the older the age, the longer the
time of induction in paediatrics [24]. The time of
induction was faster in the ketamine—midazolam
group probably because of the effects of midazolam
in producing muscle relaxation, anxiolysis and cen-
tral sedation [15].
It is found that induction of anaesthesia with
ketamine; with or without midazolam was unevent-
ful, cardiovascularly stable and no signs of upper
airway irritation. Many writers expressed that the
salivation increases after ketamine [1,2]. Salivation
could have been a serious matter for the surgeon
during the operation. In our study, salivation was
prevented by additional use of atropine.
It is known that; recovery agitation or emergence
reactions are bound to dosage of ketamine and that
complications are rarely seen in children [13]. How-
ever, there were many conflicting data which
claimed that emergence reactions of patients varied
between 5 and 100%. In general, following ketamine
administration emergence reactions were shown to
prolonged 2—3 weeks [18,25]. However, in two chil-
dren the adverse effects of ketamine lasting 2—9
months had been reported previously [26]. It is our
opinion that these long lasting adverse effects may
be emerged as a result of several visual-operations
based psychological problems of patients; not by
ketamine.
The effects of midazolam on the emergence
reactions after ketamine are controversial. Studies
have claimed that adjunctive midazolam does not
reduce recovery agitation after ketamine [20,27];
our study showed that midazolam can partly dimin-
ish recovery agitation after ketamine anaesthesia.
Interestingly we noticed that in these studies
[20,27]; ketamine were given in low dosage and
for premedication. On the other hand, a study in
which ketamine—midazolam were used as a sole
anaesthetic for prolonged abdominal surgery
claimed that ketamine—midazolam anaesthesia
provided better recovery and hemodynamic condi-
tions without emergency reactions [12].
The aetiology of postoperative vomiting is multi-
factorial. In theory, patients undergoing tonsillect-
omy or adenotonsillectomy may be at increased risk
of bleeding and thus vomiting. The reported inci-
dence of vomiting after tonsillectomy in children is
as high as 75% [28]. In our study, the incidence of
retching or vomiting is 67.9% in group K and 32.1% in
group KM. Similar to study in which claimed that the
administration of benzodiazepines has been asso-
ciated with a decrease in nausea vomiting among
the paediatric patients who have been performed
ophthalmic surgery [29]; our results show that giving
ketamine with midazolam reduced retching and
vomiting during the first 4 h after extubation. The
G. Erk et al.
significantly higher incidence of retching and vomit-
ing 4 h after extubation in group K could be because
of a direct emetic effect of ketamine or because of
emetic effects of tonsillectomy.
Taking into consideration that the reported inci-
dence of postoperative vomiting after tonsillectomy
without ketamine is as high as 75%, it could be
thought that emetic effects of ketamine need to
be investigated in another study.
Some studies demonstrated that midazolam had
antidopaminergic activity at clinical dosage and
reduces postoperative nausea vomiting after keta-
mine anaesthesia [10,20,30]. It can be thought that
antiemetic effects of midazolam having a reason for
the decrease of retching and vomiting in group KM,
in the first 4 h after extubation. All of the patients
who had retching and vomiting were given antie-
metic therapy in the first 4 h after extubation in our
study, retching and vomiting were significantly
lower in group K (32.1%) then group KM (42.9%) in
the 4—24 h after extubation.
In conclusion, we have demonstrated that
emergence reactions were partly diminished
by adjunctive midazolam and vomiting—retching
was decreased after ketamine anaesthesia by
midazolam.
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