Comparative study of hyoscine doses as antisialagogue for patients receiving ketofol sedation undergoing colonoscopy procedures.

OBJECTIVE: To compare the effects of different regimens of hyoscine as antisialagogue in patients undergoing ketofol sedation for colonoscopy procedures. PATIENTS AND METHODS: In this prospective double-blind randomized controlled trial 200 American Society of Anesthesiologists I-II aged 20-60-year-old undergoing colonoscopy were randomly assigned into four equal groups, group A received 5 mg hyoscine intravenous, group B received 10 mg, group C received 20 mg intravenous, and control group (D) that was received saline. All patients were sedated using ketofol titrated to achieve Ramsey Sedation Score 4, hemodynamic variables and occurrence of increased secretions were evaluated and recorded.
RESULTS: Hyoscine in a dose of 10 mg was the optimum dose to achieve least salivation with the least side effect while hyoscine 5 mg was not efficient to achieve dry field or good surgical conditions. However, hyoscine 20 mg achieved dry field and fair surgical conditions in expenses of tachycardia.
CONCLUSION: Hyoscine 10 mg was the least effective dose that significantly reduced hypersalivation in patients receiving ketofol sedation for colonoscopy procedures, this dose was as effective as 20 mg in draying secretion but with significantly less tachycardia.

RCT Entities:   Population Interventions Outcomes

INTRODUCTION

A colonoscopy is an outpatient procedure in which the large intestine (colon and rectum) is examined; colonoscopy is a short procedure that is usually done under sedation by giving sedative agents like propofol or dissociative drugs like ketamine with or without opioids, to help these patients to tolerate colonoscopy procedures without impairing cardiac or respiratory functions.[1234]

Hyoscine butylbromide is an anticholinergic agent with affinity to muscarinic receptors located on the gastrointestinal tract smooth muscles and has an antispasmodic effect, drying secretion, and less tachycardia effects.[5]

Antisialagogues have been recommended to counteract the increased tracheobronchial secretions and hypersalivation caused by ketamine. Hyoscine has an antimuscarinic effect; atropine and glycopyrrolate may be used.[6]

In this study, hyoscine has been examined in different doses as an antisialagogue and antispasmodic that will counteract ketamine effect on salivary glands and will improve surgical conditions.

PATIENTS AND METHODS

This study is a double-blinded randomized, parallel study that was conducted in Cairo University Teaching Hospital between January 2014 and January 2015. This study was conducted after approval of Scientific and Ethical Committee of Anesthesiology Department in Kasr El Aini Hospital, Cairo University. A written informed consent was taken from each patient in this trial. 200 patients of (American Society of Anesthesiologists) physical status I-II patients of both sexes aged 20–60 years scheduled for therapeutic or diagnostic colonoscopy under ketofol sedation were included in this study. Patients with allergy to study drugs, cardiovascular disease (uncontrolled hypertension, tachycardia, congestive heart failure, and coronary artery disease), and decompensated hepatic or renal failure, glaucoma, and prostatic patients were excluded.

Patients were randomly assigned into one of four groups 50 patients in each group. The allocation sequence was done using a randomized computer-generated sequence done by an investigator not involved in the clinical management or data collection.

Preprocedural evaluation included history taking, physical examination, and laboratory investigations (complete blood count, kidney and liver function tests, and coagulation profile).

Before sedation, the study drugs were prepared as follow: Ketamine and propofol mixture (ketofol) is 5 mg/mL ketamine (ketamine 50mg/ml Sigma Pharmaceuticals, Egypt) and 5 mg/mL propofol (diprivan, 10% astrazeneca), 1:1 mixture. Hyoscine N-butylbromide 20 mg/ml (Buscupan®, 20 mg/ml Boehringer Inglheim), 10 min before sedation hyoscine given very slowly either 5 mg (group A), 10 mg (group B), 20 mg (group C) and saline (group D). All the syringes were prepared and diluted in 20 ml syringe by an investigator who did not share in the assessment or the anesthesia, while another anesthetist or technician, who was blinded to syringes, documented all patients' parameters including salivation (double blinded to patient and follow-up investigator).

Baseline heart rate, blood pressure, and oxygen saturation were continuously monitored and recorded, oxygen mask was applied then ketofol was titrated very slowly to reach Ramsey Sedation Score 4 or 5 and the patients were observed visually for increased salivation using Thomas-Stonell and Greenberg classification which consists of a 5-point scale for severity: 1 - dry, 2 - mild (wet lips), 3 - moderate (wet lips and chin), 4 - severe (clothing damp), and 5 - profuse (clothing, hands, and objects).[7]

Heart rate, blood pressure, and oxygen saturation at 1, 5, 10, 15, 20, 25, 30, 40, 50, and 60 min after sedation were recorded.

Surgical condition will be recorded by asking the surgeon to identify either good relaxation or bad conditions (either happy or not happy).

The sample size was calculated by setting α error of 0.05 and power of 0.8, calculation produced a minimal sample size of 45 patients in each arm.

Data were coded and entered using the statistical package IBM Corp. Released 2013. IBM SPSS Statistics for Windows, Version 22.0. (Armonk, NY: IBM Corp). Data were summarized using mean and standard deviation for quantitative variables and frequencies (number of cases) and relative frequencies (percentages) for categorical variables. Comparisons between quantitative variables were done using ANOVA with the post-hoc test. Comparisons between the values measured at baseline, after 15 min, 30 min, 45 min, and 60 min in each group were done using repeated measure ANOVA (general linear model). For comparing categorical data, Chi-square (c2) test was performed. The exact test was used instead when the expected frequency is <5. P < 0.05 was considered as statistically significant.

RESULTS

Over the period of the study in endoscopy unit in Kasr El Aini Hospital 356 patients were admitted to do colonoscopy with 286 patients were fulfilling study inclusion criteria, 200 of them agreed and signed consent to be included in the study. Each patient signed was randomly allocated to one of the four groups [Figure 1].

Figure 1

Participant flow diagram

Regarding the demographic data (age, sex, and body mass index) and duration of the procedure, there was no statistical difference among groups [Tables 1 and 2].

Table 1

Demographic data among four groups

Table 2

Gender among the four groups

Hyoscine with a dose of 5 mg in group A showed neither improvement of salivation score nor increase in heart rate or blood pressure in comparison to group D (control group). On the other hand, hyoscine with both doses of 10 and 20 mg (group B and C respectively) showed improvement of salivation score as the score was maintained at the level I (P < 0.05).

Diagram in Figure 2 illustrates the salivation score in all the four groups over the follow-up time (60 min) which clearly demonstrates the significant effect on salivation that was occurred in both groups B and C. on the other hand, it shows the weak effect of hyoscine 5 mg on salivation which always coincided with control group D.

Figure 2

Salivation versus time in the four groups

Likewise, there was an increase in the heart rate with statistical significance in group C (P < 0.05) to reach its peak after 15 min and then to return back to the baseline after 30 min. Meanwhile, there was no recorded complication such as arrhythmia, hypotension, or hypertension.

Also, the diagram in Figure 3 illustrates the sudden climbing of the heart rate at min 15 in group C in comparison to the rest of groups that showed almost a stationary line.

Figure 3

Heart rate versus time in the four groups

Mean arterial blood pressure in all the four groups show very minimal or even no increase at all over the procedure.

Surgeon satisfaction (surgical conditions): All surgeons were certified as a specialist by Cairo University Credential and Privilege Committee. In this study, surgeon was asked only one question to specify their satisfaction collectively; are you happy with this surgical condition or not? Yes considered as 1, and no considered as 0, there was a clinical and statistical significant in both groups B and C with hyoscine 10 and 20 mg, respectively regarding surgeon satisfaction. On the other hand, surgeons were not happy by surgical conditions in both groups A and D (hyoscine 5 mg and placebo) this dissatisfaction was great in group D (placebo) and with clinical significance but not statistical one [Table 3].

Table 3

Surgical satisfaction and surgical conditions among four groups

DISCUSSION

In the current study, it was found that administration of hyoscine as an antisialagogue to patients receiving ketofol sedation for colonoscopy procedures was an effective method to reduce hypersalivation induced by ketamine. The doses 20 mg and 10 mg of hyoscine nearly as effective as each other in drying secretions but the dose of 20 mg hyoscine was associated with significant tachycardia, so the dose of 10 mg is recommended as a premedication drug of choice in colonoscopy procedures as it also relieved abdominal discomfort and pain.

Hyoscine butylbromide with its affinity to muscarinic receptors gave both benefits to the surgeon and the patient in the form of its antispasmodic effect and antisialagogue effect respectively.

Mato et al.,[6] conducted a study for management of drooling in disabled patients using scopolamine skin patches and concluded that it is an effective and safe method, although it requires appropriate patient selection and is not free from adverse effects. Lewis et al.,[8] found that drooling was completely resolved in one-third of cases in a group of 11 children with mental disability and moderate to severe drooling. Elazzazi and Saleh[9] conducted a study to compare the effects of different doses of the anticholinergic atropine as an antisialagogue for patients receiving ketamine-midazolam undergoing gamma knife radiosurgery and concluded that atropine 0.3 mg was the least effective dose that significantly reduced hypersalivation in patients receiving ketamine sedation. In contrast to the present study Diamant and Feinmesser[10] found that hyoscine butylbromide 20 mg had slight antisialagogue effect with marked effect on pulse rate which made it unsuitable for premedication but this may be due to the use of large dose of hyoscine and limited number of patients (4 patients only).

CONCLUSION

Hyoscine 10 mg was the least effective dose that significantly reduced hypersalivation in patients receiving ketofol sedation for colonoscopy procedures, this dose was as effective as 20 mg in draying secretion but with significantly less tachycardia.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest