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ORIGINAL ARTICLE
Year : 2021  |  Volume : 7  |  Issue : 1  |  Page : 58-62

Comparison of Ketamine, Lignocaine, and Fentanyl on Dose Requirement of Propofol in Patients Undergoing ERCP: A Randomized Controlled Trial


Institute of Liver and Biliary Sciences, Vasant Kunj, New Delhi, India

Date of Submission10-Feb-2021
Date of Decision10-Feb-2021
Date of Acceptance16-Feb-2021
Date of Web Publication28-Apr-2021

Correspondence Address:
MD Neha Garg
Department of Anaesthesia, Institute of Liver and Biliary Sciences, Vasant Kunj, New Delhi, 110070
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/mamcjms.mamcjms_11_21

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  Abstract 


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 Oct 24];7:58-62. Available from: https://www.mamcjms.in/text.asp?2021/7/1/58/314873




  Introduction Top


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.[1] 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.[2],[3] 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.[4],[5] This analgesic effect of lignocaine may be due to its action both at central and peripheral receptors.[6],[7] It may be because of blockage of sodium channels, N-methyl-D-aspartate receptor, glycinergic systems, or certain potassium and calcium channels.[8],[9] 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 Top


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 Top


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,[4] 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.[10]


  Results Top


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].
Table 1 Demographics and intra-procedure detail of the three groups

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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.
Table 3 Comparison of pain scores of the three groups

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  Discussion Top


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.[10] 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.[10]

Kim et al.[11] 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.[11]

In another study conducted by Akhondzadeh et al.[12] 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.[12] 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.[12]

Lignocaine has been found to decrease visceral pain in some animal studies.[13],[14] It has been found to have analgesic and opioid sparing effect in many studies.[15],[16] 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.[17] 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.[18],[19],[20]

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

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Joo JD, In JH, Kim DW et al. The comparison of sedation quality, side effect and recovery profiles on different dosage of remifentanil patient-controlled sedation during breast biopsy surgery. Korean J Anesthesiol 2012;63:431-5.  Back to cited text no. 1
    
2.
Li J, Wang G, Xu W, Ding M, Yu W. Efficacy of intravenous lidocaine on pain relief in patients undergoing laparoscopic cholecystectomy: a meta-analysis from randomized controlled trials. Int J Surg 2018;50:137-45.  Back to cited text no. 2
    
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Zhao JB, Li YL, Wang YM et al. Intravenous lidocaine infusion for pain control after laparoscopic cholecystectomy: a meta-analysis of randomized controlled trials. Medicine (Baltimore) 2018;97:e9771.  Back to cited text no. 3
    
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Kaba A, Laurent SR, Detroz BJ et al. Intravenous lidocaine infusion facilitates acute rehabilitation after laparoscopic colectomy. Anesthesiology 2007;106:11-8.  Back to cited text no. 4
    
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Altermatt FR, Bugedo DA, Delfino AE et al. Evaluation of the effect of intravenous lidocaine on propofol requirements during total intravenous anaesthesia as measured by bispectral index. Br J Anaesth 2012;108:979-83.  Back to cited text no. 5
    
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Devor M, Wall PD, Catalan N. Systemic lidocaine silences ectopic neuroma and DRG discharge without blocking nerve conduction. Pain 1992;48:261-8.  Back to cited text no. 6
    
7.
Hodgson PS, Liu SS. Epidural lidocaine decreases sevoflurane requirement for adequate depth of anesthesia as measured by the Bispectral Index monitor. Anesthesiology 2001;94:799-803.  Back to cited text no. 7
    
8.
Lauretti GR. Mechanisms of analgesia of intravenous lidocaine. Rev Bras Anestesiol 2008;58:280-6.  Back to cited text no. 8
    
9.
Fassoulaki A, Melemeni A, Zotou M, Sarantopoulos C. Systemic ondansetron antagonizes the sensory block produced by intrathecal lidocaine. Anesth Analg 2005;100:1817-21.  Back to cited text no. 9
    
10.
Forster C, Vanhaudenhuyse A, Gast P et al. Intravenous infusion of lidocaine significantly reduces propofol dose for colonoscopy: a randomised placebo-controlled study. Br J Anesth 2018;121:1059-64.  Back to cited text no. 10
    
11.
Kim JE, Choi JB, Koo BN, Jeong HW, Lee BH, Kim SY. Efficacy of intravenous lidocaine during endoscopic submucosal dissection for gastric neoplasm: a randomized, double-blind, controlled study. Medicine 2016;95:e3593.  Back to cited text no. 11
    
12.
Akhondzadeh R, Ghomeishi A, Nesioonpour S, Nourizade S. A comparison between the effects of propofol-fentanyl with propofol-ketamine for sedation in patients undergoing endoscopic retrograde cholangiopancreatography outside the operating room. Biomed J 2016;39:145-9.  Back to cited text no. 12
    
13.
Ness TJ. Intravenous lidocaine inhibits visceral nociceptive reflexes and spinal neurons in the rat. Anesthesiology 2000;92:1685-91.  Back to cited text no. 13
    
14.
Ness TJ, Randich A. Which spinal cutaneous nociceptive neurons are inhibited by intravenous lidocaine in the rat? Reg Anesth Pain Med 2006;31:248-53.  Back to cited text no. 14
    
15.
Kuo CP, Jao SW, Chen KM et al. Comparison of the effects of thoracic epidural analgesia and iv infusion with lidocaine on cytokine response, postoperative pain and bowel function in patients undergoing colonic surgery. Br J Anaesth 2006;97:640-6.  Back to cited text no. 15
    
16.
Herroeder S, Pecher S, Schönherr ME et al. Systemic lidocaine shortens length of hospital stay after colorectal surgery: a double-blinded, randomized, placebo-controlled trial. Ann Surg 2007;246:192-200.  Back to cited text no. 16
    
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Yam MF, Loh YC, Tan CS, Khadijah Adam S, Abdul Manan N, Basir R. General pathways of pain sensation and the major neurotransmitters involved in pain regulation. Int J Mol Sci 2018;19:2164.  Back to cited text no. 17
    
18.
Marret E, Rolin M, Beaussier M, Bonnet F. Meta-analysis of intravenous lidocaine and postoperative recovery after abdominal surgery. Br J Surg 2008;95:1331-8.  Back to cited text no. 18
    
19.
Wu CT, Borel CO, Lee MS et al. The interaction effect of perioperative cotreatment with dextromethorphan and intravenous lidocaine on pain relief and recovery of bowel function after laparoscopic cholecystectomy. Anesth Analg 2005;100:448-53.  Back to cited text no. 19
    
20.
Lauwick S, Kim DJ, Michelagnoli G et al. Intraoperative infusion of lidocaine reduces postoperative fentanyl requirements in patients undergoing laparoscopic cholecystectomy. Can J Anaesth 2008;55:754-60.  Back to cited text no. 20
    


    Figures

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    Tables

  [Table 1], [Table 2], [Table 3]



 

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