Published online: 10.05.

2019

Original Article 381

Postoperative Nausea and Vomiting Following

Craniotomy: Risk Factors and Complications in Context of
Perioperative High-dose Dexamethasone Application
Till Burkhardt1,2,
Patrick Czorlich1,
Klaus Christian Mende1 Annika Treitz1 Rainer Kiefmann3
Manfred Westphal1 Nils Ole Schmidt1

1 Department of Neurosurgery, University Medical Center Hamburg-
Eppendorf, Hamburg, Germany
2 Department of Neurosurgery, Friedrich-Ebert-Hospital,
Neumünster, Germany
3 Department of Anaesthesiology, University Medical Center
Hamburg-Eppendorf, Hamburg, Germany
Address for correspondence Patrick Czorlich, MD, Department of
Neurosurgery, University Medical Center Hamburg-Eppendorf,
Martinistrasse 52, 20246 Hamburg, Germany
(e-mail: p.czorlich@uke.de).

J Neurol Surg A 2019;80:381–386.

Abstract Introduction Postoperative nausea and vomiting (PONV) is common in patients after

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craniotomy and may lead to severe postoperative complications. The aim of this study
was to identify risk factors and postoperative complications associated with PONV in
the context of perioperative high-dose dexamethasone administration.
Patients and Methods In this prospective single-center study, all patients planned for
elective craniotomy for supra- and infratentorial lesions were eligible to be included.
Any PONV in a 24-hour period after craniotomy was recorded and analyzed with regard
to time to postoperative complications and the administration of perioperatively
administered high-dose dexamethasone.
Results The overall PONV rate of 421 patients during a 9-month period was 18.1% (76
patients). Multivariate analysis revealed a significant association of PONV with female
sex, infratentorial localization, age, and history of PONV. There was no association
between PONV and postoperative complications such as intracranial hemorrhage,
cerebrospinal fluid (CSF) leaks, or pneumonia. Perioperative administration of high-
dose dexamethasone for prophylactic prevention of edema was the only significant risk
factor for postoperative complications (odds ratio [OR]: 3.34; confidence interval [CI],
Keywords 1.39–8.05; p < 0.01) with a highly significant association with the occurrence of CSF
► PONV leaks (OR: 6.85; CI, 1.62–29.05; p < 0.01).
► craniotomy Conclusion The low PONV rate of 18.1% in this study may be the result of the frequent
► complications perioperative administration of high-dose dexamethasone for the prevention of
► dexamethasone edema. Our data indicate that perioperative high-dose dexamethasone is significantly
► CSF leaks associated with CSF leaks and can therefore not be recommended on a regular basis.

Introduction
Postoperative nausea and vomiting (PONV) is a common side
effect of general anesthesia and is reported in 20 to 30% of all


Till Burkhardt and Patrick Czorlich contributed equally.
patients1 and in up to 49% following neurosurgical cranial
procedures.2,3 The overall rate of PONV is related to many
factors such as patient age (with a negative correlation and
therefore a higher risk of PONV in children), sex (with a
higher risk in female patients), a positive correlation with

received © 2019 Georg Thieme Verlag KG DOI https://doi.org/

July 27, 2018 Stuttgart · New York 10.1055/s-0039-1685194.
accepted ISSN 2193-6315.
October 17, 2018
published online
May 10, 2019
382 Postoperative Nausea and Vomiting Following Craniotomy
obesity, positive history of PONV or motion sickness, and
nonsmoking status.4,5 In addition, other treatment-related
factors were identified as the type of anesthetic drug, with a
significantly lower risk to develop PONV with total intrave-
nous anesthesia (TIVA),6 type of surgical procedure, and
duration of the surgical procedure/anesthesia.4,7,8
Most studies regarding PONV focus on its prevention or
treatment because it is regarded as a fundamental part of pre-
and postoperative care. Thus several drugs were evaluated for
this purpose.9–13 Although nausea may lead to less severe
consequences such as decreased well-being of the patient,
delayed mobilization, and possibly prolonged duration of
hospital stay,14 the physical act of vomiting has the potential
for deleterious consequences because it elevates the risk for
postoperative aspiration-associated pneumonia, and it also, if
prolonged, leads to dehydration and electrolyte imbalance.5
The consequences of PONV in the neurosurgical setting have
yet to be evaluated. It may, in the short term, increase intra-
cranial pressure or cerebral intravascular pressure and there-
fore put patients at risk for infections due to suture
insufficiency with cerebrospinal fluid (CSF) leakage and for
intracranial hemorrhage (ICH).15 Due to the very limited intra-
cranial space and the high mortality of postoperative ICH of
 30%,16 these have to be avoided under any circumstances.
One reason for the limited intracranial space is a cerebral
edema that already exists before the craniotomy or even
extends intra- and postoperatively. To prevent the increase
of such edema, the perioperative administration of high-dose-
dexamethasone is feasible as described previously.3 Therefore
we investigated the incidence of PONV in a cohort of 421
patients as well as specific neurosurgical risks following PONV
in patients who underwent elective craniotomy in the context
of perioperative high-dose dexamethasone administration.
Patients and Methods
Inclusion and Exclusion Criteria
All adult patients who underwent elective cranial neurosur-
gery from September 2013 to May 2014 were screened pro-
spectively for inclusion in this study. Patients were
subclassified into different groups by the underlying pathol-
ogy and location such as supratentorial or infratentorial
lesions, surgery for seizure control, surgery on the cerebello-
pontine angle (CPA), and neurovascular surgery. Patients who
underwent transsphenoidal surgery were excluded, as were
patients undergoing ventriculoperitoneal or ventriculoatrial
shunting and patients undergoing deep brain stimulation.
Patients who were deemed as emergent cases were also
excluded from the study, as were patients in which anesthesia
could not be discontinued within 24 hours after the operation.
Anesthesiological Procedures
All patients were assessed preoperatively according to the
Apfel score.17 General anesthesia was induced with 0.2 to 0.3
mg/kg sufentanil intravenously, followed by 2 to 3 mg/kg
propofol intravenously or 0.2–0.3 mg/kg etomidate. Intrave-
nous atracurium (0.5 mg/kg) or succinylcholine (1–1.5 mg/
kg) was used to facilitate tracheal intubation. Anesthesia was
Journal of Neurological Surgery—Part A Vol. 80 No. A5/2019
Burkhardt et al.
maintained with propofol (5–8 mg/kg/hour) as TIVA. Gran-
isetron (1 mg) and/or dexamethasone (4–8 mg) were admi-
nistered for the prevention of PONV if deemed necessary by
the attending anesthesiologist.
For the prevention of cerebral edema, 40 mg dexametha-
sone was administered perioperatively, if found necessary by
the neurosurgeon in charge. Analgesic management con-
sisted of intermittent boluses of sufentanil or an infusion
of remifentanil (0.05–0.5 mg/kg/minute). All patients were
transferred to a specialized neurosurgical intensive care unit
(ICU) and were extubated after discontinuation of general
anesthesia.
Outcome Measures
PONV in this study was defined as both nausea as well as the
urge to vomit and vomiting itself and was screened for
24 hours after extubation by the ICU staff and documented
in an electronic patient chart (Integrated Care Management
[ICM], Dräger Medical Deutschland GmbH, Lübeck, Ger-
many) in case of PONV. All patients were screened for
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mobilization (leaving their hospital bed) and duration of
hospital stay. Postoperative complications were recorded
and classified as epicutaneous CSF leaks (with epicutaneous
loss of CSF), subcutaneous CSF leaks (with subcutaneous
collection of CSF only without any epicutaneous loss of CSF),
clinically relevant ICH, and pneumonia.
The decision to administer a medical PONV prophylaxis
and the decision to treat nausea or vomiting in the post-
operative setting was not part of the study design but part of
the routine clinical decision making of the attending physi-
cian or nurse in charge.
Statistical analysis was performed using IBM SPSS v.22
and v.23. Chi-square tests in combination with cross tables
were used for data evaluation. Backward and forward binary
logistic regression analysis was performed to identify vari-
ables of significant impact on PONV and the incidence of
complications. A 95% confidence interval (CI) was deemed
significant in all statistic-testing modalities.
This study was in accordance with local, institutional, and
general ethical guidelines and was approved by the local
ethics committee. All patients gave written informed consent
about the use of all patient- and treatment-related data.
Results
Patient Characteristics
A total of 546 patients from September 2013 to May 2014
were screened for inclusion, and 421 patients with 239
females (56.8%) and 182 males (43.2%), with a median age
of 57 years (range: 18–90 years) met the inclusion criteria.
The median duration of in-hospital stay was 9 days (range:
1–143 days). ►Table 1 presents the details of the underlying
diagnosis and localization of the pathologies.
PONV, Risk Factors, and Medication
Overall, 53 patients had a positive history for PONV (12.6%),
18 patients reported episodes of motion sickness (4.3%), and
98 patients were smokers (23.3%). A total of 110 patients
 Postoperative Nausea and Vomiting Following Craniotomy Burkhardt et al. 383

Table 1 Patient characteristics

Characteristic Overall PONV No PONV

Patients, n (%) 421 76 (18.1) 345 (81.9)
Female sex (%) 239 (56.8) 59 (77.6) 180 (52.2)
Age, y (range) 55.4 (18–90) 51.3 (18–90) 56.3 (18–85)
Mobilization, d (range) 1.54 (0–28) 1.62 (1–10) 1.53 (0–28)
Hospitalization, d (range) 12.0 (2–143) 11.4 (5–62) 12.1 (2–143)
Pathology localization, n (%)
Supratentorial 333 (79.1) 50 (65.8) 283 (82.0)
Infratentorial 88 (20.9) 26 (34.2) 62 (18.0)
Type of surgery, n (%)
Supratentorial lesion 255 (60.6) 38 (50.0) 217 (62.9)
Infratentorial lesion 70 (16.6) 17 (22.4) 53 (15.4)
Lesions of the CPA 18 (4.3) 9 (11.8) 9 (4.6)
Vascular surgery 49 (11.6) 6 (7.9) 43 (12.5)
Surgery for epilepsia 29 (6.9) 6 (7.9) 23 (6.7)

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Complications, n (%)
Subcutaneous CSF leaka 34 (8.1) 5 (6.6) 29 (8.4)
b
Epicutaneous CSF leak 12 (2.9) 1 (1.3) 11 (3.2)
Hemorrhage 17 (4) 4 (5.3) 13 (3.8)
Pneumonia 4 (1) 1 (1.3) 3 (0.9)

Abbreviations: CPA, cerebellopontine angle; CSF, cerebrospinal fluid; PONV, postoperative nausea and vomiting.
a
With subcutaneous CSF collection only.
b
With epicutaneous loss of CSF.

(26.1%) received medical prophylaxis with 4 mg dexametha- PONV and Complications

sone or granisetron preoperatively to prevent PONV.
The overall PONV rate in our study cohort was 18.1%
(n ¼ 76) (►Table 1) with a significant increase to 29.5%
(n ¼ 26 of 88; p ¼ 0.002) in patients undergoing infratentor-
ial surgery including surgery of pathologies in the CPA.
Univariate analysis revealed that surgery in the CPA was
significantly associated with PONV (odds ratio [OR]: 3.12;
p < 0.05) (►Table 2). As part of patient-related items of the
Apfel score, a history of PONV or of female sex were sig-
nificantly associated with PONV but not smoking or a history
of motion sickness. Multivariate analysis confirmed the
significant association of female sex, infratentorial localiza-
tion, history of PONV, and age with PONV.
In the overall study cohort, only 26.1% of patients received
a PONV prophylaxis with 4 mg dexamethasone or granise-
tron. The rate of PONV was not significantly different
between those patients with or without a PONV prophylaxis,
most likely because independently of a PONV prophylaxis,
most patients (n ¼ 303) received a dose of 40 mg dexa-
methasone perioperatively for edema prevention. Patients
receiving 40 mg dexamethasone had a lower risk of experi-
encing PONV compared with patients not receiving any high-
dose steroids (15.8% with PONV, n ¼ 48/303 patients with
40 mg dexamethasone versus 23.5% with PONV, n ¼ 28/118
patients without 40 mg dexamethasone), but this did not
reach statistical significance (►Table 2).
To assess the potential role of PONV for postoperative
surgical morbidity, complications were classified as subcu-
taneous or epicutaneous CSF leaks, clinically relevant ICH,
and pneumonia. In our cohort of 421 patients, the overall
complication rate as defined by our criteria was 12.4%
(n ¼ 52) (►Table 1). The occurrence of PONV was not asso-
ciated with the postoperative complication rate in our study
cohort (►Table 3). Pneumonia due to aspiration occurred in
only 4 cases (1%), and 17 patients (4.0%) had a clinically
relevant postoperative hemorrhage. Both complications
were not associated with PONV. Furthermore, neither the
time to mobilization after surgery was affected by PONV
compared with patients without PONV (1.5  1.9 versus
1.6  1.3 days, respectively; p ¼ 0.61) nor the duration of
in-hospital stay (12.1  9.8 versus 11.4  7.7 days, respec-
tively; p ¼ 0.49).
A total of 34 patients (8.1%) showed signs of a CSF leak
with subcutaneous collection only, and 12 patients (2.9%)
developed a postoperative CSF leak with epicutaneous loss of
CSF (►Table 1). The risk of developing a CSF leak (sub- and
epicutaneous) was not significantly associated with PONV
(►Table 2) but occurred more often after infratentorial
procedures with a significantly associated risk for CSF leak
with an epicutaneous loss of CSF (OR: 3.99; 95% CI, 1.25–
12.69; p < 0.05). In addition, univariate analysis identified
smoking (OR: 2.32; 95% CI, 1.06–5.10; p < 0.05) and

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384 Postoperative Nausea and Vomiting Following Craniotomy Burkhardt et al.

Table 2 Risk factors of PONV, complications, and CSF leaks

PONV
Univariate
OR Lower CI Upper CI p
Infratentorial localization 2.37 1.37 4.11 < 0.01
Lesions of the CPA 3.12 1.07 9.12 < 0.05
Dexamethasone 40 mg 0.61 0.36 1.02 0.059
Smoking 0.66 0.35 1.24 0.20
Motion sickness 1.58 0.54 4.61 0.40
History of PONV 3.02 1.61 5.66 < 0.01
Female sex 3.12 1.78 5.68 < 0.01
Multivariate
Female sex 3.02 1.65 5.50 < 0.01
Infratentorial approach 2.14 1.20 3.80 < 0.01
History of PONV 2.37 1.23 4.57 ¼ 0.01
Years of age 0.98 0.96 0.99 ¼ 0.01

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Complications
Univariate
PONV 0.94 0.44 2.03 ¼ 0.88
Infratentorial approach 0.66 0.30 1.45 ¼ 0.30
Smoking 1.52 0.78 2.96 ¼ 0.22
Dexamethasone 40 mg 2.86 1.19 6.92 < 0.05
Female sex 0.87 0.49 1.57 ¼ 0.65
Multivariate
Dexamethasone 40 mg 3.34 1.39 8.05 p < 0.01
CSF leaks
Univariate
a
Infratentorial approach 0.98 0.41 2.33 ¼ 0.96
b
Infratentorial approach 3.99 1.25 12.69 < 0.05
Smoking 2.32 1.06 5.10 < 0.05
Dexamethasone 40 mg 5.90 1.39 25.09 < 0.01
PONV 0.41 0.05 3.18 ¼ 0.37
Multivariate
Smoking 2.36 1.06 5.24 < 0.05
Dexamethasone 40 mg 11.00 1.47 82.26 ¼ 0.02

Abbreviations: CI, confidence interval; CPA, cerebellopontine angle; CSF, cerebrospinal fluid; OR, odds ratio; PONV, postoperative nausea and vomiting.
a
All CSF leaks.
b
Only CSF leaks with epicutaneous loss of CSF.
Note: Boldface denotes statistically significant.

perioperative administration of 40 mg dexamethasone (OR:
5.90; 95% CI, 1.39–25.09; p < 0.01) as risk factors for the
occurrence of CSF leak, which was confirmed in the multi-
variate analysis.
Postoperative Complications and High-Dose
Dexamethasone
Although in our study cohort PONV was not associated with
an increased risk of postoperative complications, we found a
significant increased overall risk for complications by 3.34
(95% CI, 1.39–8.05; p < 0.01) after perioperative adminis-
tration of 40 mg dexamethasone for the prevention of intra-
or postoperative swelling/edema (►Table 3). The periopera-
tive administration of high-dose dexamethasone was the
only significant factor for postoperative complications with a
highly significant association with the occurrence of CSF
leaks (OR: 5.90; 95% CI, 1.39–25.09; p < 0.01; OR: 6.85;
95% CI, 1.62–29.05; p < 0.01, respectively) (►Tables 2 and 3).

Journal of Neurological Surgery—Part A Vol. 80 No. A5/2019

 Postoperative Nausea and Vomiting Following Craniotomy
Table 3 Impact of 40 mg dexamethasone
40 mg dexamethasone
Univariate
OR Lower CI Upper CI
Overall 3.34 1.39 8.05
complications
CSF leaks overall 6.85 1.62 29.05
Epicutaneous 4.41 0.56 34.5
Subcutaneous 10.07 1.35 75.27
Hemorrhage 3.02 0.68 13.42
Pneumonia 1.17 0.12 11.36
Abbreviations: CI, confidence interval; CSF, cerebrospinal fluid; OR, odds
ratio.
Note: Boldface denotes statistically significant.
Discussion
PONV is a known problem in patients undergoing craniot-
omy2,3 with potentially dangerous consequences in neuro-
surgical patients because elevated blood pressure and
elevated intracranial pressure during vomiting may cause
hemorrhage and CSF leakage. The aim of this study was to
identify whether and to what degree PONV is hazardous in
neurosurgical patients undergoing craniotomy in the context
of perioperative high-dose dexamethasone administration.
In summary, we found a lower rate of 18% of PONV compared
with previously reported data2,3 and no association between
the occurrence of PONV and major complications such as
postoperative ICH, suture insufficiencies with CSF leaks, or
pneumonia. Furthermore, the time to mobilization after
surgery was not extended in PONV patients, and the length
of hospital stay was not prolonged by PONV.
We found a positive correlation of infratentorial surgery
and an elevated PONV rate in our cohort that is in line with
the results of Fabling et al, Manninen et al, and Kurita
et al,18–20 who found an increased risk of PONV in patients
undergoing infratentorial surgery. However, these studies
were all performed retrospectively. Furthermore, Manninen
et al19 compared awake craniotomies, which are not per-
formed in infratentorial surgery, with general anesthesia,
making the results prone to overinterpretation. Another
study did not find any correlation of surgical site and
PONV rate,3 although the authors indicated the possibility
of little power to substantiate their findings, which is not the
case in our study.
In this study, PONV did not carry a higher risk of compli-
cations such as hemorrhage, CSF leaks, or nonsurgical issues.
However, due to the low incidence of PONV in our study
cohort, the data have limited power to rule out PONV
completely as dangerous to neurosurgical patients. The low
incidence of PONV in our study might be related to the result
of the frequent perioperative administration of high-dose
dexamethasone for the prevention of edema and swelling,
despite the fact that this effect failed to reach a statistical
level of significance. A single low dose of 4 mg dexametha-
Burkhardt et al. 385
sone is a well-established prophylactic regimen for the
prevention of PONV,13 which was shown in numerous
trials.13,15,21–23 The single shot of high-dose dexamethasone
to prevent perioperative edema and swelling is a common
p practice at our department and seems to be common prac-
tice with variants in other neurosurgical departments as
< 0.01
well.3,24–26 However, our analysis revealed a highly signifi-
cant correlation between the administration of high-dose
< 0.01
dexamethasone and postoperative complications such as CSF
¼ 0.12 leaks. Our data extend the findings of a recent report of
< 0.01 significantly higher rates of wound infections after admin-
¼ 0.13 istration of high-dose dexamethasone during instrumented
surgery for cervical myelopathy.24
¼ 0.89
Steroids, with dexamethasone as its most potent version,
have a well-established, swift immunodepressive effect that
may explain insufficiencies in wound healing,27–31 and they
may further explain the higher rate of CSF leaks in neurosur-
gical patients receiving dexamethasone. Postoperative hemor-
rhages were linked to intraoperative administration of
dexamethasone as well,32,33 although its underlying mechan-
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ism is not fully understood. Animal studies clearly showed the
interference of dexamethasone with platelet function,34 but
human trials failed to show a suppressive effect of steroids
(prednisolone) on bleeding time and platelet function.35 The
potential role of dexamethasone in this regard is unknown. A
reasonable speculation for an elevated risk for postoperative
hemorrhage is the inhibition of repair processes in wounds, a
common side effect of glucosteroids.36
In the light of these findings, a highly significant correla-
tion of steroid administration at high dosages and post-
operative complications, we have since changed our modus
operandi and dispensed with high doses of dexamethasone
as common practice for the prevention of perioperative
edema and swelling. Instead, administration of high-dose
dexamethasone is now limited only to patients in whom
severe life-threatening swelling is observed or highly antici-
pated by the surgeon in charge.
Conclusion
We found a low rate of 18% of PONV after craniotomy and no
association of PONV with major postoperative complica-
tions, time to mobilization after surgery, or length of hospital
stay. The true incidence of PONV in our study cohort may be
masked by the frequent perioperative administration of
high-dose dexamethasone for the prevention of edema and
swelling, and therefore the risk of hazardous consequences
due to PONV after craniotomy cannot be fully excluded.
However, our data clearly indicate adverse effects of perio-
perative high-dose dexamethasone in a neurosurgical set-
ting with a significant risk to develop CSF leaks. We therefore
recommend avoiding the administration of perioperative
high-dose dexamethasone for the routine prophylactic pre-
vention of edema, especially because no prospective data of
its benefit during neurosurgical procedures exist.
Conflict of Interest
None.
Journal of Neurological Surgery—Part A Vol. 80 No. A5/2019
386 Postoperative Nausea and Vomiting Following Craniotomy
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