|Year : 2021 | Volume
| Issue : 1 | Page : 58-62
Comparison of Ketamine, Lignocaine, and Fentanyl on Dose Requirement of Propofol in Patients Undergoing ERCP: A Randomized Controlled Trial
Preeti Dhahiya, Neha Garg, Mahesh Arora, Deepak Tempe
Institute of Liver and Biliary Sciences, Vasant Kunj, New Delhi, India
|Date of Submission||10-Feb-2021|
|Date of Decision||10-Feb-2021|
|Date of Acceptance||16-Feb-2021|
|Date of Web Publication||28-Apr-2021|
MD Neha Garg
Department of Anaesthesia, Institute of Liver and Biliary Sciences, Vasant Kunj, New Delhi, 110070
Source of Support: None, Conflict of Interest: None
Introduction: Propofol is the most common drug used for providing sedation due to its short duration of action and early recovery. However, it may be associated with hypotension, desaturations, and bradycardia and does not provide analgesia, due to which various adjuncts are used along with it. Lignocaine decreases the doses of propofol and inhalational agent when used for visceral surgeries. Thus, we conducted a study to compare the dose of propofol along with lignocaine, ketamine, and fentanyl for sedation in endoscopic retrograde cholangiopancreatography (ERCP) procedure. Methods: A total of 105 patients were randomized into three groups. Sedation was provided by intravenous bolus injection of propofol 1 mg/kg in all patients followed by infusion of 0.5 mg/kg/hour. In group K bolus dose of intravenous ketamine was 0.5 mg/kg followed by infusion of 0.3 mg/kg/hour, in group L patients were given intravenous bolus of lignocaine 1.5 mg/kg followed by a infusion of 2 mg/kg/hour, in group F the matched volume of saline and 1 μ/kg fentanyl were administered. Intermittent boluses of propofol were given in all three groups in response to patients’ discomfort evidenced by grimaces, movement, or increase in heart rate or mean arterial pressure by >20% of baseline. The total dose of propofol consumed in the three groups was noted. Results: The total dose of propofol consumed and post-procedure abdominal pain was significantly higher in the fentanyl group but was comparable in lignocaine and ketamine groups. Conclusion: Lignocaine and ketamine were equally effective in deceasing propofol requirement and in preventing post-ERCP abdominal pain.
Keywords: Endoscopic retrograde cholangiopancreatography, fentanyl, ketamine, lignocaine, pain
|How to cite this article:|
Dhahiya P, Garg N, Arora M, Tempe D. Comparison of Ketamine, Lignocaine, and Fentanyl on Dose Requirement of Propofol in Patients Undergoing ERCP: A Randomized Controlled Trial. MAMC J Med Sci 2021;7:58-62
|How to cite this URL:|
Dhahiya P, Garg N, Arora M, Tempe D. Comparison of Ketamine, Lignocaine, and Fentanyl on Dose Requirement of Propofol in Patients Undergoing ERCP: A Randomized Controlled Trial. MAMC J Med Sci [serial online] 2021 [cited 2021 Jun 13];7:58-62. Available from: https://www.mamcjms.in/text.asp?2021/7/1/58/314873
| Introduction|| |
Endoscopic retrograde cholangiopancreatography (ERCP) is done under sedation in view of its long duration of action and pain during the procedure. A variety of drugs are used for sedation in ERCP room such as propofol, fentanyl, ketamine, dexmedetomidine, and midazolam. Propofol is the most popular of these drugs due to its short duration of action, faster onset, and faster recovery, but it may lead to side effects such as apnea, desaturation, hypotension, and bradycardia. Thus, a number of adjuncts are often used along with propofol to decrease these side effects by decreasing the dose of propofol. In addition, since propofol does not provide analgesia some drugs are given to provide analgesia during the procedure. Ketamine has long been used with propofol to provide analgesia and sedation. However, use of ketamine is associated with side effects such as nausea, vomiting, dizziness, and hallucinations. These psychomimetic side effects can be decreased by simultaneous use of propofol, midazolam but may not be completely eliminated.
There are various stages during the ERCP procedure which may necessitate usage of additional propofol, such as during scope insertion, during duodenal papilla dilation, esophageal dilatation, etc., which may lead to additional doses of propofol and thus may lead to side effects mentioned above. Thus midazolam, fentanyl, and ketamine are used in adjunct to propofol. Recently lignocaine has been used in a few studies to provide sedation during endoscopic removal of gastric papilloma with better outcomes than propofol alone. Lignocaine has been found to decrease the dose of opioids and a reduction in pain intensity in many studies on patients undergoing abdominal surgeries., It has been shown to decrease the intensity of visceral pain in animal models. It decreases the need of volatile anesthetic agent by 30% to 40% and of propofol during surgeries., This analgesic effect of lignocaine may be due to its action both at central and peripheral receptors., It may be because of blockage of sodium channels, N-methyl-D-aspartate receptor, glycinergic systems, or certain potassium and calcium channels., Thus using lignocaine infusion as an adjunct to propofol may decrease the propofol requirement and lessen the risk of desaturations and hypotension due to propofol with no additional side effects. Thus we conducted a prospective randomized controlled trail to see if adding lignocaine infusion during ERCP helps to decrease the propofol requirement and thus the side effects incurred due to its usage and provides adequate analgesia such as that provided by ketamine and fentanyl during the procedure for providing sedation to these patients.
| Methodology|| |
After approval by the ethical committee and written informed consent by the patients, a prospective, double-blind, randomized controlled trial was conducted. All patients undergoing ERCP between 18 and 65 years of age at Institute of Liver and Biliary Sciences between July 2019 and November 2019 were included in the study. Patients with renal failure, liver failure/cirrhosis, epilepsy/seizure disorder, cardiac arrhythmias, known allergy to lignocaine/ketamine/propofol, failure to give consent, psychosis, raised intracranial pressure or raised intraocular pressure, raised intragastric pressure, porphyria, ischemic heart disease, or vascular aneurysm were excluded from the study.
Patients were divided into three groups by computer generated random numbers and sequentially numbered opaque sealed envelope technique before the start of procedure. Sedation was provided by intravenous bolus injection of propofol 1 mg/kg in all patients followed by infusion of 0.5 mg/kg/hour. In addition, in group K bolus dose of ketamine 0.5 mg/kg was administered by intravenous route followed by infusion of 0.3 mg/kg/hour during the procedure. In group L patients were given an intravenous bolus of lignocaine 1.5 mg/kg followed by a continuous infusion of 2 mg/kg/hour. In group F the matched volume of saline was given and 1 μ/kg fentanyl was administered just before endoscope insertion. Intravenous boluses of propofol 20 to 30 mg was given in all three groups in response to patients discomfort evidenced by grimaces, movement, or hemodynamic changes (increase in heart rate [HR] >20% or in mean arterial pressure [MAP] >20% of baseline).
Baseline blood pressure and HR was noted for patients before the start of procedure in the recovery room. The HR and MAP were noted at 5 minute intervals for all patients during the procedure. The total dose of propofol consumed during the procedure was noted in all the three groups. Post-procedure pain score was noted once the patient was shifted in the recovery room at 5, 15, 30, and 45 minutes. Post-procedure throat pain was also noted once the patient was shifted in recovery. Also nausea, vomiting, hallucinations, and urinary retention were noted till 4 hours after procedure in all three groups.
The primary objective of the study was to see if there was any difference in the total propofol consumed in the three groups. The secondary objective was to see if there was any difference in the hemodynamics (HR and MAP) during the procedure, desaturation episodes during procedure, post-procedure throat pain, or post-procedure abdominal pain between the three groups.
| Statistical analysis|| |
The data will be entered in Microsoft Excel format and will be analyzed using SPSS software version 22 (IBM SPSS Statistics for Windows, Version 22.0. Armonk, NY: IBM Corp). The techniques applied were chi square or Fischer exact test whichever applicable. The continuous data was compared by applying student t test or Mann–Whitney U test whichever applicable. Data was analyzed by using repeated measures, analysis of variance (ANOVA) test followed by post hoc comparison by Bonferroni method. Besides this, the repeated measure analysis was also carried out to find out the changes over the period of time. Followed by post hoc comparison by fisher least significant difference (LSD) method. Significance was seen at 5% level.
Assuming that in standard treatment dose requirement of propofol without any adjuvant drug is 300 ± 128 mg, with ketamine it is 200 ± 109 mg with alpha error 5% (0.17 for each group) and power 90% with 1:1 ratio. We enrolled 105 cases, 30 in each group with additional 5 assuming 15% dropout; we enrolled 35 in each group. Thus total sample size was 105. The allocation of treatment was done randomly by computer generated random number and sealed envelope technique.
| Results|| |
A total of 105 patients who underwent ERCP at Institute of Liver and Biliary Sciences were enrolled in our study. All the three groups were comparable in age, sex, BMI, duration of procedure, diagnosis, type of procedure, and ASA grading [Table 1].
Total amount of propofol required to maintain sedation was significantly higher in the fentanyl group than in the other two groups (P < 0.001). It was comparable for ketamine and lignocaine group (P = 0.726) but was significant between ketamine and fentanyl (P < 0.0001) and between lignocaine and fentanyl group (P < 0.001). Only two patients in fentanyl group had desaturation below 96% and were corrected by giving jaw thrust. There were no episodes of hypotension in any of the groups. Only one patient in lignocaine and two patients each in ketamine and fentanyl group had movements during scope manipulation which was not significant (P > 0.05). There was no difference in the MAP or HR of the three groups during the procedure [Figure 1] and [Figure 2].
|Figure 1 Comparison of MAP at different time points between the three groups during ERCP. ERCP, endoscopic retrograde cholangiopancreatography; MAP, mean arterial pressure.|
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|Figure 2 Comparison of HR at different time points between the three groups during ERCP. ERCP, endoscopic retrograde cholangiopancreatography; HR, heart rate.|
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The incidence of post-procedure throat pain was not significantly different in either of the groups (P = 0.760) [Table 2].
|Table 2 Total propofol consumed and incidence of throat pain in the three groups|
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There was a significant difference in the post-procedure pain in the groups at all times (P < 0.05). On further analysis, there was a significant difference between the post-procedure pain in between ketamine and fentanyl groups (P < 0.05) and between the fentanyl and lignocaine groups (P < 0.05) but there was not much difference between the ketamine and lignocaine groups (P > 0.05) [Table 3]. A number of patients had post-procedure hallucinations, dizziness, diplopia, and urinary retention. Only one patient in ketamine group had vomiting.
| Discussion|| |
The major finding of the study was propofol requirement was significantly decreased by using intravenous lignocaine or ketamine, but not by using fentanyl. Also the incidence of post-procedure pain was significantly less in lignocaine and ketamine group. Though fentanyl and ketamine have been compared in many studies and administration of lignocaine has been tried in a few studies as an adjunct to sedation but the three drugs have never been compared together for sedation procedures.
Forster et al. reported a 50% decrease in propofol requirement for sedation in colonoscopy by using lignocaine and ketamine. In addition they also found a significant decrease in the post-colonoscopy pain by using lignocaine infusion similar to our study.
Kim et al. also reported similar finding as ours but their study was conducted in endoscopic submucosal resection of early gastric neoplasm which may have pain due to traction of gastric mucosa than simple dilatation of viscera in ERCP. They compared lignocaine with placebo and found a significant decrease in amount of fentanyl consumed, involuntary movements, post-procedure pain, and throat pain in lidocaine group than placebo.
In another study conducted by Akhondzadeh et al. in patients undergoing ERCP, they found a significant decrease in the post-procedure pain after 1 hour in patients who had been given ketamine and propofol than patients who had been given fentanyl and propofol which is similar to our study. However, they found an increased incidence of apnea following 1 μ/kg fentanyl with 0.5 mg/kg of propofol which was not found in our study despite using the same doses of drugs. Addition of propofol to ketamine decreases the incidence of hallucinations, nausea, and vomiting caused by ketamine and thus none of the patients in our study developed any psychomimetic side effects.
Lignocaine has been found to decrease visceral pain in some animal studies., It has been found to have analgesic and opioid sparing effect in many studies., Owing to its local anesthetic effect, lignocaine is found to decrease the conduction of unmyelinated C-type fibers which are also responsible for conduction of nociceptive pain. Lignocaine has also been found to decrease the postsurgery opioid requirement and in decrease in the incidence of postoperative ileus indirectly decreasing the side effect of opioid on the gut in many abdominal surgeries and laparoscopic surgeries.,,
There are few limitations of this study. We did not assess the preoperative pain in the patients that may be present due to the disease physiology, making the patients more prone to pain and requiring more drug amount for sedation and analgesic drugs. Though pain following ERCP is minimal, we did not follow for visceral pain in the post-procedure period.
Thus we conclude that lignocaine and propofol is as effective as ketamine and propofol for sedation in patient undergoing ERCP and using fentanyl as adjunct to propofol is not as effective as lignocaine or ketamine for providing sedation and for post-procedure pain.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2]
[Table 1], [Table 2], [Table 3]