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336 Original article

Comparison between different atropine doses as an

antisialagogue for patients receiving ketamine-midazolam
undergoing gamma knife radiosurgery
Hesham M. Elazzazi, Adham A. Saleh

Department of Anesthesiology, Intensive Care, Objectives

and Pain Management, Faculty of Medicine,
Comparing different atropine doses to detect the least effective dose as an antisialagogue, in
Ain-Shams University, Cairo, Egypt
patients receiving ketamine-midazolam sedation for gamma knife radiosurgery.
Correspondence to Adham A. Saleh, MD, Patients and methods
Department of Anesthesiology, Intensive Care,
The study included 120 American Society of Anesthesiologists Physical Status I, II patients
and Pain Management, Faculty of Medicine,
Ain-Shams University, Cairo, Egypt (age range 1860 years) undergoing gamma knife radiosurgery. The patients were randomly
e-mail: [email protected] divided into three equal groups. Patients in group A received atropine 0.5 mg intravenously,
atropine 0.3 mg intravenously in group B, whereas patients in group C received 0.1 mg
Received 21 May 2014
Accepted 20 June 2014 atropine intravenously. All patients received intravenous ketamine 0.5 mg/kg, plus intravenous
midazolam 1 mg. Baseline heart rate and blood pressure, change in heart rate, and occurrence
Ain-Shams Journal of Anesthesiology
of increased secretions were recorded.
2014, 07:336339
Results
A total of 120 patients undergoing gamma knife radiosurgery were included in the study. Only
one patient in group A and two patients in group B showed increased secretions (2.5 and
5%, respectively), whereas in group C 15 patients experienced increased secretions (37.5%).
None of the patients who experienced increased secretions required suctioning of secretions.
With regard to the change in heart rate, group A patients had significant increase in heart rate,
whereas the changes in heart rate in group B and C were not significant.
Conclusion
The dose of 0.3 mg atropine used in group B showed the same efficacy as an antisialagogue
as the dose of 0.5 mg atropine that was used in group A, and was significantly more efficient
than the dose of 0.1 mg atropine used in group C patients, who experienced significant increase
of secretions. In addition, group B patients did not experience the significant increase in heart
rate that was experienced by group A patients.

Keywords:
gamma knife, ketamine, midazolam

Ain-Shams J Anesthesiol 07:336339

2014 Department of Anesthesiology, Intensive Care and Pain Managment,
Faculty of Medicine, Ain-Shams University, Cairo, Egypt
1687-7934

centers from perceiving visual, auditory, or painful

Introduction
stimuli. It is characterized by rapid onset of action and
Gamma knife radiosurgery is a very unique form
profound sedation and analgesia. Fortunately, laryngeal
of therapeutic radiology performed using the
reflexes are maintained and respiratory depression is
gamma knife, which is a noninvasive neurosurgical
tool, depending on gamma radiation. This type of rare. That is why ketamine has become a very popular
radiation therapy can shrink small brain tumors or agent for procedural sedation and analgesia [2].
block abnormal blood vessels, for example, cavernous
Side effects of ketamine include vomiting and
hemangioma. Many beams of gamma radiation join
unpleasant emergence phenomenon. Ketamine also
together just to focus on the lesion, providing a very
intense dose of radiation, without a surgical incision. leads to hypersalivation and increased tracheobronchial
secretions. The most feared complication of ketamine
Procedural sedation and analgesia is a technique of sedation necessitating advanced airway management
administering sedatives (e.g. midazolam, propofol) or is laryngospasm, which occurs more commonly in the
dissociative agents (e.g. ketamine), with or without presence of increased secretions [3].
opioid analgesics (e.g. fentanyl), to help patients
tolerate procedures such as gamma knife radiosurgery, Therefore, antisialagogues have been recommended
without impairing cardiorespiratory function [1]. as a routine adjunct, a view particularly favored by
anesthetists. Atropine with its antimuscarinic effects
Ketamine is a phencyclidine derivative that dissociates is most commonly used, with glycopyrrolate being an
the cortex from the limbic system, preventing the higher alternative drug [4].
1687-7934 2014 Department of Anesthesiology, Intensive Care and Pain Management,
Faculty of Medicine, Ain-Shams University, Cairo, Egypt DOI: 10.4103/1687-7934.139560
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Atropine in gamma knife radiosurgery Elazzazi and Saleh 337

from the nose or mouth, gargling sounds, the need for

Aim of the work
suctioning, or stridor.
The aim of the study was to compare between
different atropine doses as an antisialagogue agent, Demographic features (age, sex, body weight) and
with the least effect on heart rate for patients duration of treatment were recorded. Heart rate was
receiving ketamine-midazolam sedation for gamma recorded just before start of the injection of intravenous
knife radiosurgery. ketamine and atropine, and 1, 5, 10, and 20 min after
injection. With regard to the occurrence of increased
secretions, the aforementioned events were considered
Patients and methods as increased secretions, if happened.
This study was conducted at Gamma Knife Center,
Nasser Institute (Cairo, Egypt), in collaboration with Statistical analysis
Ain Shams University. After getting an informed Sample size was calculated using Epilnfo version 6.0,
patient consent, 120 patients of either sex, with setting the type-1 error () at 0.05 and the power
the American Society of Anesthesiologists (ASA) (1-B) at 0.8. Calculation produced a minimal sample
IorII physical status classification, aged 1860 years, size of 40 cases in each group.
scheduled for gamma knife treatment for brain tumors,
were randomly divided into three groups using simple Data were analyzed using statistical program for
randomization tables and sealed envelopes: group A social science (SPSS version 18.0; SPSS Inc., Chicago,
included 40 patients who received 0.5 mg atropine Illinois, USA). Quantitative data were expressed
intravenously, group B patients received 0.3 mg as mean SD. Qualitative data were expressed as
atropine intravenously, and patients of group C received frequency and percentage.
0.1 mg atropine intravenously. All patients received
intravenous ketamine 0.5 mg/kg plus intravenous The following tests were conducted: a one-way analysis
midazolam 1 mg. of variance when comparing between more than two
means; and 2-test of significance was used to compare
Exclusion criteria for both groups included patients proportions between two qualitative parameters.
with ASA III or IV physical status classification, P-value of less than 0.05 was considered significant,
patients with compromised cardiac, respiratory, renal, P-value of 0.01 was considered as highly significant,
or hepatic disease, patients with increased ICT, or and P-value of more than 0.05 was considered
patients with known hypersensitivity to ketamine or insignificant.
midazolam.

Methods Results
Patients had fasted for at least 8 h before the The study included 120 patients (75 male and 45
procedure. Baseline vital data were recorded (heart female), who were randomly divided into three equal
rate, blood pressure, and respiratory rate). After groups according to the atropine dose (0.5, 0.3, and 0.1
intravenous cannulation, patients of the three groups mg, respectively). All patients underwent gamma knife
received ketamine 0.5 mg/kg intravenously (Ketamine, radiosurgery for brain tumors.
50 mg/ml; Sigma Pharmaceuticals, Egypt) plus
midazolam 1 mg intravenously (Midathetic, 5 mg/ml; With regard to age, sex, body weight of patients,
Amoun pharmaceuticals, Egypt). Group A patients baseline hemodynamic data, and duration of
received atropine 0.5 mg intravenously (Atropine, treatment, no statistically significant differences
1 mg/ml; Misr Pharmaceuticals, Egypt), patients were found among the three groups (P > 0.05)
of group B received atropine 0.3 mg intravenously, (Table 1).
and patients of group C received 0.1 mg atropine
intravenously. Only one patient (2.5%) in group A (who received
atropine 0.5 mg), and two patients (5%) in group B
The patients were observed visually during the (who received atropine 0.3 mg), had increased
treatment inside the treatment room through a closed secretions, whereas 15 patients (37.5%) had increased
audio video circuit. All patients were monitored secretions in group C (who received atropine 0.1 mg).
by pulse oximetry (Homedics Px-100 Deluxe) for Comparison between the three groups showed that
arterial oxygen saturation and pulse rate throughout the incidence of increased secretions was significantly
the treatment. The patients were observed for lower in groups A and B than in group C (P < 0.05)
hypersalivation manifested by drooping of secretions (Table 2) (Fig. 1).
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338 Ain-Shams Journal of Anesthesiology

Table 1 Patients age, sex, body weight, baseline heart rate, blood pressure, respiratory rate, and duration of treatment
Parameters Mean SD ANOVA
Group A Group B Group C F P-value
Age (years) 37.75 11.76 41.00 11.61 39.88 10.47 0.854 0.428
Sex [N (%)]
Female 19 (47.5) 14 (35) 12 (30) 2 = 2.772 0.250
Male 21 (52.5) 26 (65) 28 (70)
Body weight (kg) 76.50 11.56 80.13 9.90 79.38 13.12 1.088 0.340
Baseline HR/min 79.75 6.40 80.13 4.73 77.25 10.06 1.781 0.173
Systolic BP 126.38 7.76 129.88 13.28 125.63 11.78 1.646 0.197
Diastolic BP 75.00 6.41 78.13 6.86 76.75 9.37 1.673 0.192
Baseline RR/min 15.53 1.57 16.55 2.14 15.90 2.18 2.739 0.089
Duration of treatment (min) 34.83 8.75 39.10 7.78 37.28 7.64 2.825 0.073
ANOVA, analysis of variance; BP, blood pressure; HR, heart rate.

Table 2 Relation among groups with regard to the number Figure 1

of cases with increased secretions
Secretions N (%) A and A and B and
B C C
Group A Group B Group C
Yes 1 (2.50) 2 (5.00) 15 (37.50) >0.05 0.003 0.001
No 39 (97.50) 38 (95.00) 25 (62.50)
Total 40 (100.00) 40 (100.00) 40 (100.00)
2 23.922
P-value <0.01

After administration of the medications, group A

patients had significant increase in heart rate (P<0.05),
whereas patients of groups B and C had statistically
nonsignificant increase in heart rate (P > 0.05)
(Table3).
Relation among groups with regard to the number of cases with
increased secretions.

Discussion
Administration of atropine as an antisialagogue to in all cases, and the use of atropine as an adjunct
patients receiving ketamine sedation for gamma knife for intramuscular ketamine sedation in children
radiosurgery was an effective technique to reduce significantly reduces hypersalivation.
hypersalivation induced by ketamine. The doses of 0.5
and 0.3 mg of atropine showed nearly the same efficiency Brown et al. [6] conducted a prospective observational
in decreasing secretions, but the dose of 0.1mg atropine study over 3 years on 1090 pediatric patients who
did not prevent the increase in secretions in 15 patients received ketamine sedation in the emergency
in group C (37.5% of patients). Atropine dose 0.3 mg department, and they used 100-mm visual analogue
also caused significantly lower incidence of tachycardia scale to rate excessive salivation. Of the 1090
than the dose of 0.5 mg, which was used in group A ketamine sedations, 947 were administered without
patients. adjunctive atropine, and surprisingly, their results
showed that 92% of these subjects had salivation
Heinz et al. [5] conducted a prospective, randomized, score of 0 mm.
double-blind study, including a total of 83 patients, aged
13 months14.5 years, who required ketamine procedural Green et al. [7] published a secondary analysis of an
sedation in a tertiary emergency department. Patients observational database of 8282 ED ketamine sedations
were randomized to receive 0.01 mg/kg of atropine assembled from 32 studies. They compared the relative
or placebo. All received 4 mg/kg of intramuscular incidence of adverse events including airway adverse
ketamine. Hypersalivation occurred in 11.4% of events and laryngospasm (most probably owing
patients administered atropine compared with 30.8% increased secretions) between children who received
of patients administered placebo. They concluded that atropine, glycopyrrolate, or no anticholinergic. Their
ketamine sedation was successful and well tolerated results showed that glycopyrrolate was associated
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Atropine in gamma knife radiosurgery Elazzazi and Saleh 339

Table 3 Comparison between three groups with regard to changes in heart rate
Groups Mean SD P-value
Baseline 1 min 5 min 10 min 20 min
Group A 79.75 6.40 86.72 11.40 94.63 14.18 86.11 10.36 80.60 7.86 <0.01
Group B 80.13 4.73 83.01 7.78 83.93 11.96 82.09 9.86 80.90 7.01 >0.05
Group C 77.25 10.06 81.00 11.86 79.11 9.92 80.63 7.06 78.30 5.61 >0.05
P-value of group A was highly significant with regard to the increase in heart rate and is indicated in bold.

with significantly more airway and respiratory adverse significantly less tachycardia. More studies are needed
events than either atropine or no anticholinergic. to confirm this finding.

Another clinical study was conducted by Islam

et al. [8] to evaluate the effect of different atropine
doses on heart rate during reversal of nondepolarizing Acknowledgments
neuromuscular blockade. They divided the patients Conflicts of interest
None declared.
into three groups (A, B, and C) according to the dose
of atropine administered (0.02, 0.015, and 0.01 mg/kg,
respectively). They recommended the use of atropine
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