|Year : 2014 | Volume
| Issue : 3 | Page : 336-339
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, and Pain Management, Faculty of Medicine, Ain-Shams University, Cairo, Egypt
|Date of Submission||21-May-2014|
|Date of Acceptance||20-Jun-2014|
|Date of Web Publication||27-Aug-2014|
Adham A Saleh
Department of Anesthesiology, Intensive Care, and Pain Management, Faculty of Medicine, Ain-Shams University, Cairo
Source of Support: None, Conflict of Interest: None
Comparing different atropine doses to detect the least effective dose as an antisialagogue, in patients receiving ketamine-midazolam sedation for gamma knife radiosurgery.
Patients and methods
The study included 120 American Society of Anesthesiologists Physical Status I, II patients (age range 1860 years) undergoing gamma knife radiosurgery. The patients were randomly 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 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 of increased secretions were recorded.
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.
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
|How to cite this article:|
Elazzazi HM, Saleh AA. Comparison between different atropine doses as an antisialagogue for patients receiving ketamine-midazolam undergoing gamma knife radiosurgery. Ain-Shams J Anaesthesiol 2014;7:336-9
|How to cite this URL:|
Elazzazi HM, Saleh AA. Comparison between different atropine doses as an antisialagogue for patients receiving ketamine-midazolam undergoing gamma knife radiosurgery. Ain-Shams J Anaesthesiol [serial online] 2014 [cited 2019 May 23];7:336-9. Available from: http://www.asja.eg.net/text.asp?2014/7/3/336/139560
| Introduction|| |
Gamma knife radiosurgery is a very unique form of therapeutic radiology performed using the gamma knife, which is a noninvasive neurosurgical tool, depending on gamma radiation. This type of radiation therapy can shrink small brain tumors or block abnormal blood vessels, for example, cavernous hemangioma. Many beams of gamma radiation join together just to focus on the lesion, providing a very intense dose of radiation, without a surgical incision.
Procedural sedation and analgesia is a technique of administering sedatives (e.g. midazolam, propofol) or dissociative agents (e.g. ketamine), with or without opioid analgesics (e.g. fentanyl), to help patients tolerate procedures such as gamma knife radiosurgery, without impairing cardiorespiratory function .
Ketamine is a phencyclidine derivative that dissociates the cortex from the limbic system, preventing the higher centers from perceiving visual, auditory, or painful stimuli. It is characterized by rapid onset of action and profound sedation and analgesia. Fortunately, laryngeal reflexes are maintained and respiratory depression is rare. That is why ketamine has become a very popular agent for procedural sedation and analgesia .
Side effects of ketamine include vomiting and unpleasant emergence phenomenon. Ketamine also leads to hypersalivation and increased tracheobronchial secretions. The most feared complication of ketamine sedation necessitating advanced airway management is laryngospasm, which occurs more commonly in the presence of increased secretions .
Therefore, antisialagogues have been recommended as a routine adjunct, a view particularly favored by anesthetists. Atropine with its antimuscarinic effects is most commonly used, with glycopyrrolate being an alternative drug .
Aim of the work
The aim of the study was to compare between different atropine doses as an antisialagogue agent, with the least effect on heart rate for patients receiving ketamine-midazolam sedation for gamma knife radiosurgery.
| Patients and methods|| |
This study was conducted at Gamma Knife Center, Nasser Institute (Cairo, Egypt), in collaboration with Ain Shams University. After getting an informed patient consent, 120 patients of either sex, with the American Society of Anesthesiologists (ASA) I or II physical status classification, aged 18-60 years, scheduled for gamma knife treatment for brain tumors, were randomly divided into three groups using simple randomization tables and sealed envelopes: group A included 40 patients who received 0.5 mg atropine intravenously, group B patients received 0.3 mg atropine intravenously, and patients of group C received 0.1 mg atropine intravenously. All patients received intravenous ketamine 0.5 mg/kg plus intravenous midazolam 1 mg.
Exclusion criteria for both groups included patients with ASA III or IV physical status classification, patients with compromised cardiac, respiratory, renal, or hepatic disease, patients with increased ICT, or patients with known hypersensitivity to ketamine or midazolam.
Patients had fasted for at least 8 h before the procedure. Baseline vital data were recorded (heart rate, blood pressure, and respiratory rate). After intravenous cannulation, patients of the three groups received ketamine 0.5 mg/kg intravenously (Ketamine, 50 mg/ml; Sigma Pharmaceuticals, Egypt) plus midazolam 1 mg intravenously (Midathetic, 5 mg/ml; Amoun pharmaceuticals, Egypt). Group A patients received atropine 0.5 mg intravenously (Atropine, 1 mg/ml; Misr Pharmaceuticals, Egypt), patients of group B received atropine 0.3 mg intravenously, and patients of group C received 0.1 mg atropine intravenously.
The patients were observed visually during the treatment inside the treatment room through a closed audio video circuit. All patients were monitored by pulse oximetry (Homedics Px-100 Deluxe) for arterial oxygen saturation and pulse rate throughout the treatment. The patients were observed for hypersalivation manifested by drooping of secretions from the nose or mouth, gargling sounds, the need for suctioning, or stridor.
Demographic features (age, sex, body weight) and duration of treatment were recorded. Heart rate was recorded just before start of the injection of intravenous 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 as increased secretions, if happened.
Sample size was calculated using Epilnfo version 6.0, setting the type-1 error (͵) at 0.05 and the power (1-B) at 0.8. Calculation produced a minimal sample size of 40 cases in each group.
Data were analyzed using statistical program for social science (SPSS version 18.0; SPSS Inc., Chicago, Illinois, USA). Quantitative data were expressed as mean ± SD. Qualitative data were expressed as frequency and percentage.
The following tests were conducted: a one-way analysis of variance when comparing between more than two means; and χ2 -test of significance was used to compare proportions between two qualitative parameters. P-value of less than 0.05 was considered significant, P-value of 0.01 was considered as highly significant, and P-value of more than 0.05 was considered insignificant.
| Results|| |
The study included 120 patients (75 male and 45 female), who were randomly divided into three equal groups according to the atropine dose (0.5, 0.3, and 0.1 mg, respectively). All patients underwent gamma knife radiosurgery for brain tumors.
With regard to age, sex, body weight of patients, baseline hemodynamic data, and duration of treatment, no statistically significant differences were found among the three groups (P > 0.05) [Table 1].
|Table 1 Patients' age, sex, body weight, baseline heart rate, blood pressure, respiratory rate, and duration of treatment|
Click here to view
Only one patient (2.5%) in group A (who received atropine 0.5 mg), and two patients (5%) in group B (who received atropine 0.3 mg), had increased secretions, whereas 15 patients (37.5%) had increased secretions in group C (who received atropine 0.1 mg). Comparison between the three groups showed that the incidence of increased secretions was significantly lower in groups A and B than in group C (P < 0.05) [Table 2] [Figure 1].
|Figure 1: Relation among groups with regard to the number of cases with increased secretions|
Click here to view
|Table 2 Relation among groups with regard to the number of cases with increased secretions|
Click here to view
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) [Table 3].
|Table 3 Comparison between three groups with regard to changes in heart rate|
Click here to view
| Discussion|| |
Administration of atropine as an antisialagogue to patients receiving ketamine sedation for gamma knife radiosurgery was an effective technique to reduce hypersalivation induced by ketamine. The doses of 0.5 and 0.3 mg of atropine showed nearly the same efficiency in decreasing secretions, but the dose of 0.1 mg atropine did not prevent the increase in secretions in 15 patients in group C (37.5% of patients). Atropine dose 0.3 mg also caused significantly lower incidence of tachycardia than the dose of 0.5 mg, which was used in group A patients.
Heinz et al.  conducted a prospective, randomized, double-blind study, including a total of 83 patients, aged 13 months14.5 years, who required ketamine procedural sedation in a tertiary emergency department. Patients were randomized to receive 0.01 mg/kg of atropine or placebo. All received 4 mg/kg of intramuscular ketamine. Hypersalivation occurred in 11.4% of patients administered atropine compared with 30.8% of patients administered placebo. They concluded that ketamine sedation was successful and well tolerated in all cases, and the use of atropine as an adjunct for intramuscular ketamine sedation in children significantly reduces hypersalivation.
Brown et al.  conducted a prospective observational study over 3 years on 1090 pediatric patients who received ketamine sedation in the emergency department, and they used 100-mm visual analogue scale to rate excessive salivation. Of the 1090 ketamine sedations, 947 were administered without adjunctive atropine, and surprisingly, their results showed that 92% of these subjects had salivation score of 0 mm.
Green et al.  published a secondary analysis of an observational database of 8282 ED ketamine sedations assembled from 32 studies. They compared the relative incidence of adverse events including airway adverse events and laryngospasm (most probably owing increased secretions) between children who received atropine, glycopyrrolate, or no anticholinergic. Their results showed that glycopyrrolate was associated with significantly more airway and respiratory adverse events than either atropine or no anticholinergic.
Another clinical study was conducted by Islam et al.  to evaluate the effect of different atropine doses on heart rate during reversal of nondepolarizing neuromuscular blockade. They divided the patients 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 0.015 mg/kg during reversal of neuromuscular blockade, because group B patients who received this dose had significantly less tachycardia than group A, and less secretions than group C.
To the best of our knowledge, this is the first clinical study on different atropine dose as an antisialagogue, as adjunct to ketamine sedation in adults undergoing gamma knife radiosurgery.
| Conclusion|| |
Atropine 0.3 mg was the least effective dose that significantly reduced hypersalivation in patients receiving ketamine sedation for gamma knife radiosurgery. This dose was significantly much more effective in decreasing secretions than the dose of 0.1 mg, and as efficient as the dose of 0.5 mg, but with significantly less tachycardia. More studies are needed to confirm this finding.
| Acknowledgments|| |
| References|| |
|1.||American College of Emergency Physicians. Clinical policy: procedural sedation and analgesia in the emergency department. Ann Emerg Med 2005; 45:177-196. |
|2.||Green SM, Rothrock SG, Lynch EL, et al. Intramuscular ketamine for pediatric sedation in the ED: safety profile in 1022 cases. Ann Emerg Med 1998; 31:688-697. |
|3.||Green SM, Krauss B. Clinical practice guideline for emergency department ketamine dissociative sedation in children. Ann Emerg Med 2004; 44:460-471. |
|4.||Holloway VJ, Husain HM, Saetta JP, et al. Accident and emergency department led implementation of ketamine sedation in paediatric practice and parental response. J Accid Emerg Med 2000; 17:25-28. |
|5.||Heinz P, Geelhoed GC, Wee C, Pascoe EM. Is atropine needed with ketamine sedation? A prospective, randomised, double blind study. Emerg Med J 2006; 23:206-209. |
|6.||Brown L, Christian-Kopp S, Sherwin TS, et al. Adjunctive atropine is unnecessary during ketamine sedation in children. Acad Emerg Med 2008; 15:314-318. |
|7.||Green SM, Roback GM, Krauss B. Anticholinergics and ketamine sedation in children: a secondary analysis of atropine versus glycopyrrolate. Acad Emerg Med 2010; 17:157-162. |
|8.||Islam MA, Shahida SM, Islam MR, Haque MM, Rashid MH, Rashid MH. Different doses of atropine on heart rate during reversal of neuromuscular blockade. Mymensingh Med J 2011; 20:595-599. |
[Table 1], [Table 2], [Table 3]