CLINICAL MYTHS AND EVIDENCE-BASED MEDICINE
Bronchoscopy in Uremic Patients
Irtaza Khan, MD,* Christina Bellinger, MD,* Carla Lamb, MD,† Robert Chin, MD,* and John Conforti, DO*
Abstract: Uremia is associated with an increased risk of bleeding by virtue
of alteration in platelet adhesion. Pulmonologists are frequently called upon
to perform flexible bronchoscopy in patients with chronic renal insufficiency.
The high blood urea nitrogen levels may predispose these patients to a high
risk of bleeding complications with bronchoscopic procedures. We carried
out a literature review to evaluate the myth that bronchoscopy is unsafe in
uremic patients.
Key Words: flexible bronchoscopy, uremia, hemorrhage, safety
(Clin Pulm Med 2010;17: 146 –148)
MYTH
Uremia increases the risk of bleeding in patients undergoing
bronchoscopy.
Flexible bronchoscopy is relatively a safe procedure but does
carry a risk of potential complications including hemorrhage. This
risk can potentially increase by coexisting medical conditions.
Bleeding is a potentially serious complication in patients with
renal failure and results from abnormalities in interactions between
platelets themselves and with the vessel wall.1 This risk increases
with the type of procedure performed and the severity of renal
failure. However, not all clinicians perform bleeding time before
performing invasive procedures in this population nor has this test
been shown to be helpful in surgical procedures. Though commonly
used in patients with renal disease, the risks of bronchoscopy
induced hemorrhage in these patients has rarely been investigated.
In 1987, the American Thoracic Society published guide-
lines2 listing conditions that can result in an increase in complica-
tions associated with bronchoscopy.
In this article we review the available literature regarding the
risk of bronchoscopy in uremic patients.
DATA
Wahidi et al3 in 2005 published a survey of the beliefs and
clinical practices among pulmonologists regarding the safety of
bronchoscopy. Of the 158 pulmonologists surveyed at the ACCP
meeting in Philadelphia in 2001, 55% of responders did not consider
elevated creatinine a potential contraindication for transbronchial
lung biopsy with 22.6% performing the procedure in patients with
creatinine levels of more than 3.0. Only 37.6% pulmonologists gave
1-deamino-8-D-arginine-vasopressin (DDAVP) before transbron-
chial lung biopsy in uremic patients with a majority (55.6%) choos-
ing not to intervene. However, the rate of hemorrhage in these
patients was not surveyed.
In 1977, Cunningham et al4 reviewed their experience of
transbronchial forceps biopsy.
Eleven of the 31 immunosuppressed patients undergoing trans-
bronchial forceps biopsy had elevated blood urea nitrogen (BUN)
From the *Pulmonary and Critical Care Medicine, Wake Forest University,
Baptist Medical Center, Winston Salem, NC; and †Tufts University School of
Medicine, MA.
Address correspondence to: John Conforti, DO, Department of Pulmonary and
Critical Care Medicine, Wake Forest University, Baptist Medical Center, Medical
Center Blvd, Winston Salen, NC 27157. E-mail: jconfort@wfubmc.edu.
Copyright © 2010 by Lippincott Williams & Wilkins
ISSN: 1068-0640/10/1703-0146
DOI: 10.1097/CPM.0b013e3181da8a0e
146 | www.clinpulm.com
ranging from 31 to 147 mg/100 mL. Bleeding in uremic patients was 3
times more than in the nonuremic population (45% vs. 15%).
Although the authors defined hemorrhage as mild (⬍20 mL)
or explosive (⬎100 mL), the quantity of bleeding and its conse-
quences were not clear in this uremic population.
Two of the above patients had initial platelet counts of 2000
and 38,000, respectively, and were treated with platelet infusions
before the procedure. The platelet count at the time of biopsy ranged
from 90,000 to 797,000. The authors made no conclusions regarding
the safety of bronchoscopy. (Category C; Table 1).5
Cordasco et al6 in 1991 published a retrospective review on
bronchoscopies performed at the Cleveland Clinic from January
1981 to December 1989. BUN of less than 25 mg/dL and creatinine
of less than 1.5 mg/dL were considered normal. Bleeding was
categorized as minimal (⬍50 mL of blood mixed with lavage fluid),
moderate (50 mL to 100 mL of bloody lavage fluid), and profuse
(⬎100 mL). Clinically significant bleeding was seen in 58 cases.
Coagulation abnormalities were seen in 3 patients. Eleven episodes
of bleeding occurred in immunosuppressed patients. Of the 58
patients who bled, 2 had renal insufficiency (BUN 29 and 40 mg/dL
and serum creatinine 2.5 and 2.3 mg/dL, respectively) and 2 patients
had end stage renal disease (ESRD). Minimal to moderate bleeding
was seen in 2 of the 4 patients with renal insufficiency (one with
chronic renal insufficiency and the other with ESRD). The other 2
(one patient with chronic renal insufficiency and one with ESRD)
had profuse bleeding. Patients with renal insufficiency who bled had
normal coagulation parameters and platelet counts, however, a
bleeding time was not performed.
The authors concluded that the degree of bleeding was related
to the type of bronchoscopy performed. Transbronchial biopsies
were associated with an increased incidence of bleeding (34 total
with 25 minimal to moderate and 9 episodes of profuse bleeding).
Bronchial brushings and endobronchial biopsies were associated
with 17 episodes of bleeding respectively (14 episodes associated
with mild to moderate and 3 with profuse bleeding in each case).
There overall risk of bleeding was low with no deaths reported.
(Category C; Table 1).5
Diette et al in 19997 performed a prospective cohort study of
all adult patients undergoing flexible bronchoscopy over a 1-year
period. A total of 720 procedures were performed including 38 in
lung transplant patients.
Although the degree of renal dysfunction was not mentioned,
6 patients were reported to have renal failure. None of the broncho-
scopies were done in the immediate postoperative period and were
performed for surveillance for rejection, airway inspection, solitary
nodule, pleural effusion, and evaluation of focal or diffuse infiltrates.
None of the patients with renal failure had hemorrhagic
complications in this study though the lung transplant patients were
5 times more likely to have the procedure terminated prematurely
for bleeding and had significantly more blood loss (928 vs. 13 mL,
P ⬍ 0.0001) at the end of the procedure. However, severity of
bleeding was not related to the degree of renal dysfunction, coagu-
lation parameters, and platelet counts.
Increase in bleeding tendencies was explained by possible
increase in inflammation and altered local hemodynamic factors
seen in lung transplant patients. (Category C; Table 1).5
Clinical Pulmonary Medicine • Volume 17, Number 3, May 2010
Clinical Pulmonary Medicine • Volume 17, Number 3, May 2010 Bronchoscopy in Uremic Patients

TABLE 1. Description of Levels of Evidence

Evidence Category Sources of Evidence
A RCTs. Rich body of data.
B RCTs. Limited body of
data.
C Nonrandomized trials.
Observational studies.
D Panel consensus judgment.
Reprinted with permission from Am J Respir Crit Care Med.5
RCT indicates randomized controlled trial.
Definition
Evidence is from endpoints of well-designed RCTs that provide a consistent pattern of
findings in the population for which the recommendation is made. category A requires
substantial numbers of studies involving substantial numbers of participants.
Evidence is from endpoints of intervention studies that include only a limited number of
patients, post hoc or subgroup analysis of RCTs, or meta-analysis of RCTs. In
general, category B pertains when few randomized trials exist, they are small in size,
or they were undertaken in a population that differs from the target population of the
recommendation, or the results are somewhat inconsistent.
Evidence is from outcomes of uncontrolled or nonrandomized trials or from
observational studies.
This category is used only in cases where the provision of some guidance was deemed
valuable but the clinical literature addressing the subject was deemed insufficient to
justify placement in one of the other categories. The Panel Consensus is based on
clinical experience or knowledge that does not meet the above-listed criteria.

TABLE 2. Grades of Recommendation and Estimates of Net Benefit*

Grades Description
†
Recommendation
A The panel strongly recommends that clinicians routinely provide (the service) to eligible patients. An “A” recommendation
indicates good evidence that (the service) improves important health outcomes and that benefits substantially outweigh harms.
B The panel recommends that clinicians routinely provide (the service) to eligible patients. A “B” recommendation indicates at
least fair evidence that (the service) improves important health outcomes and concludes that benefits outweigh harms.
C The panel recommends that clinicians routinely provide (the service) to eligible patients. A “C” recommendation indicates that
there was consensus among the panel to recommend (the service) but that the evidence that (the service) is effective is
lacking, of poor quality, or conflicting, or the balance of benefits and harms cannot be reliably determined from available
evidence.
D The panel recommends against clinicians routinely providing (the service). A “D” recommendation indicates at least fair
evidence that (the service) is ineffective or that harm outweighs benefit.
I The panel concludes that the evidence is insufficient to recommend for or against (the service). An “I” recommendation
indicates that evidence that (the service) is effective is lacking, of poor quality, or conflicting, and the balance of benefits and
harms cannot be determined, and that the panel lacked a consensus to recommend it.
Net benefit‡
Substantial Benefit greatly outweighs harm
Moderate Benefit outweighs harm
Small/weak Benefit outweighs harm to a minimally clinically important degree
None/negative Harms equal or outweigh benefit, less than clinically important
Reprinted with permission from Chest 2003;123(suppl 1):3S– 6S.
*Adapted from Am Rev Respir Dis. 1987;136:1066.2
†
The grade of the strength of recommendations is based on both the quality of the evidence and the net benefit of the service (ie, test, procedure).
‡
These levels of net benefit are based on clinical assessment. Estimated net benefit may be downgraded based on uncertainty in estimates of benefits and harms.

Kallay et al8 in 2001 published a series of 34 patients with
renal insufficiency who underwent bronchoscopy for hemoptysis.
They defined renal insufficiency as creatinine of ⬎1.5 mg/dL. Of
these patients, the etiology of bleeding was not indentified in 41% of
cases. Infections and pulmonary renal syndromes were seen 29%
and 15%, with airway injury and pulmonary embolism seen in 9%
and 6% cases, respectively.
Though a bleeding site was not identified, bronchoscopy did
lateralize the bleeding in 24% of cases. Most of the procedures
performed were bronchoalveolar lavages, but 2 patients underwent
transbronchial forceps lung biopsy. Sixteen patients were discharged
alive from the hospital and were followed up. Ten patients required
a total of 15 admissions over a period of 6 months, however, though
not specified, none of the admissions were secondary to bronchos-
copy induced bleeding. The authors did not comment on the inci-
dence of procedure induced bleeding in these patients. (Category C;
Table 1).5
In 2003, Chhajed at al9 prospectively studied 69 lung trans-
plant patients who underwent 363 transbronchial lung biopsies done
over a 2-year period. The risk factors for bleeding analyzed were
infections, number of biopsies obtained, postoperative day since
transplantation, bronchiolitis obliterans syndrome, acute rejection
and the serum creatinine level. All patients had normal platelets but
coagulation parameters were not routinely checked before each
procedure. Bleeding was classified as 0 to 25 mL or more than 25
mL (volume of mixed lavage fluid and blood at the end of the
bronchoscopy). A total of 89 (25%) procedures were associated with
a blood loss of more than 25 mL with maximum blood loss of 400
mL. Sixty-five (18%) procedures had blood loss between 50 mL and
99 mL and 13 (4%) were associated with a blood loss of more than

© 2010 Lippincott Williams & Wilkins www.clinpulm.com | 147

Khan et al
100 mL. Patients with blood loss of less than 25 mL had a mean
creatinine of 0.11 ⫾ 0.03 versus 0.10 ⫾ 0.03 in patients with more
than 25 mL blood loss. BUN values for these patients were not
mentioned. None of the analyzed factors had significant associations
with the risk and amount of bleeding. (Category C; Table 1).5
In 2005 Mehta et al10 published a 5-year retrospective review
on the rate of hemorrhage post bronchoscopy in patients with BUN
⬎30 mg/dL and/or creatinine ⬎2 mg/dL (measured within 48 hours
of the procedure). They report data on 25 patients, 7 of whom had
ESRD requiring hemodialysis. This group of patients underwent
flexible bronchoscopy within 24 hours of hemodialysis and received
DDAVP 30 minutes before bronchoscopy. Six patients had bron-
choscopic biopsy (BUN 31– 65 mg/dL, creatinine 5.2–18.7 mg/dL),
and 1 had transbronchial needle aspiration (TBNA) performed
(BUN 32 mg/dL and creatinine 4.3 mg/dL). There were no reports
of bronchoscopy induced bleeding in this group.
The other 18 patients were uremic with 12 undergoing bron-
chial biopsies, (BUN 20 – 69 mg/dL and creatinine 0.9 –2.5 mg/dL),
4 patients had TBNA (BUN 20 – 62 mg/dL and creatinine 1.1– 4.5
mg/dL), and 2 had both performed. One patient with previously
unknown coagulopathy in this group had more than 200 mL post
biopsy hemorrhage requiring intubation. This patient expired but the
exact cause of death was not given.
Another case of bleeding (50 mL) was seen post TBNA that
resolved with topical epinephrine and wedge suctioning. The authors
report an overall hemorrhage rate of 8% with a 4% rate of major
bleeding and a 4% rate of minor bleeding seen in patients not
receiving DDAVP and not undergoing hemodialysis prebronchos-
copy. This was significantly higher when compared with no hem-
orrhagic complications seen in the cohort of patients getting
DDAVP and hemodialysis prebronchoscopy. It should be noted that
the patient who had massive hemorrhage post biopsy had undiag-
nosed, pre-existing coagulopathy. It is difficult to know whether it
was the coagulopathy or uremia that was the cause of the life
threatening bleed in this patient. The authors concluded that renal
insufficiency may not increase the risk of bleeding with bronchos-
copy. (Category C; Table 1).5
CONCLUSION
Bronchoscopy plays a major role in diagnosis of pulmonary
pathologies, both in immunocompromized and immunocompetent
individuals. Uremic patients carry the perception of being higher
risk for adverse outcomes during bronchoscopy.
The risk of bleeding increases with the invasiveness of the
procedure performed with minimal bleeding seen with bronchoal-
veolar lavages and the majority of excessive blood loss seen with
transbronchial lung biopsy. The risk of bleeding also increases if the
bronchoscope is inserted nasally. Traditional approach is to use the
oral approach for bronchoscopy in patients who are deemed high
risk for bleeding to avoid epistaxis. Our review of literature
showed the paucity of data on the safety of bronchoscopy in
uremic patients. The studies we reviewed fail to come to a
conclusion regarding the contribution of uremia in bronchoscopi-
cally induced bleeding. As shown by Wahidi et al,3 the clinical
practice varies widely among pulmonologists performing bron-
choscopies in patients with renal failure.
DDAVP is the most common agent used in the uremic patient
before invasive procedures although its actual mechanism of action
148 | www.clinpulm.com
Clinical Pulmonary Medicine • Volume 17, Number 3, May 2010
is not fully understood. It does appear to provide hemostatic benefit
by the release of factor VIII and reducing the impact of the
dysfunctional von Willebrand factor. It is important to note that the
recommended dosage is 0.3 to 0.4 ␮g/kg intravenously as a single
injection. There is less evidence to support utilizing DDAVP beyond
this single dosage.11
Evidence-based recommendation in the available literature
for treatment recommendations for uremic bleeding prevention and
treatment in general are limited with small number of patients,
limitations with study design, and application of assessing platelet
function that may not be applicable today. The multifactorial com-
ponents of platelet function induced by uremia make complete
prevention of procedural related bleeding a challenge; however,
there is evidence that suggests benefits in reducing these risks can be
obtained with preprocedural dialysis and the use of DDAVP.
Based on our literature review and the lack of hemorrhagic
complications seen in patients undergoing dialysis and getting
DDAVP before bronchoscopy,10 we recommend considering pre-
bronchoscopy dialysis and DDAVP to help alleviate the risk of
bleeding in this population.
The authors conclude that there is surprisingly insufficient
evidence to guide the bronchoscopist with regards to patients with
uremia. (Grade I; Table 2).12
Randomized controlled trials to look at the safety of bron-
choscopy in patients with renal failure are warranted.
REFERENCES
1. Lohr JW, Schwab SJ. Minimizing hemorrhagic complications in dialysis
patients. J Am Soc Nephrol. 1991;2:961–975.
2. Guidelines for fiberoptic bronchoscopy in adults. American Thoracic Society.
Medical section of the American Lung Association. Am Rev Respir Dis.
1987;136:1066.
3. Wahidi M, Rocha A, Hollingsworth J, et al. Contraindications and safety of
transbronchial lung biopsy via flexible bronchoscopy: a survey of pulmonolo-
gists and review of the literature. Respiration. 2005;72:285–295.
4. Cunningham JH, Zavala DC, Corry RJ, et al. Trephine air drill, bronchial
brush, and fiberoptic transbronchial lung biopsies in immunosuppressed
patients. Am Rev Respir Dis. 1977;115:213–220.
5. Pauwels RA, Buist AS, Calverley PM, et al. Global strategy for the diagnosis,
management, and prevention of chronic obstructive pulmonary disease.
NHLBI/WHO global initiative for chronic obstructive lung disease (GOLD)
workshop summary. Am J Respir Crit Care Med. 2001;163:1256 –1276.
6. Cordasco EM, Mehta AC, Ahmad M. Bronchoscopically induced bleeding. A
summary of nine years’ Cleveland clinic experience and review of literature.
Chest. 1991;100:1141–1147.
7. Diette G, Weiner C, White P. The higher risk of bleeding in lung transplant
recipients from bronchoscopy is independent of traditional bleeding risks.
Chest. 1999;115:397– 402.
8. Kallay N, Dungan D, Adair N, et al. Hemoptysis in patients with renal
insufficiency. Chest. 2001;119:788 –794.
9. Chhajed P, Aboyoun C, Malouf M, et al. Risk factors and management of
bleeding associated with transbronchial lung biopsy in lung transplant recip-
ients. J Heart Lung Transplant. 2003;22:195–197.
10. Mehta N, Harkin T, Rom W, et al. Should renal insufficiency be a relative
contraindication to bronchoscopic biopsy? J Bronchol. 2005;12:81– 83.
11. Hedge SJ, Dehoney SB, Hooper JS, et al. Evidence based treatment recom-
mendations for uremic bleeding. Nat Clin Pract Nephrol. 2007;3:138 –153.
12. McCrory DC, Colice GL, Lewis SZ, et al. Overview of methodology for lung
cancer evidence review and guideline development. Chest. 2003;123(suppl
1):3S– 6S.
© 2010 Lippincott Williams & Wilkins