|Year : 2022 | Volume
| Issue : 1 | Page : 50-56
Influence of intraoperative lignocaine infusion on analgesia, stress response, and recovery profile in laparoscopic cholecystectomy: A randomized control study
Reena R Kadni1, G Prasanna Kumar1, Chakravarthy Joel1, Varghese K Zachariah1, Priya Pushpavathi1, Anil Kumar Narasimha2
1 Department of Anaesthesia, Bangalore Baptist Hospital, Bengaluru, Karnataka, India
2 Department of Surgery, Bangalore Baptist Hospital, Bengaluru, Karnataka, India
|Date of Submission||27-May-2021|
|Date of Decision||24-Oct-2021|
|Date of Acceptance||01-Dec-2021|
|Date of Web Publication||24-Jan-2022|
Dr. Reena R Kadni
Department of Anaesthesia, Bangalore Baptist Hospital, Bengaluru - 560 024, Karnataka
Source of Support: None, Conflict of Interest: None
INTRODUCTION: Laparoscopic cholecystectomies are performed as daycare procedures. Postoperative pain associated with it may need multimodal opioid-free approaches to fast track the recovery. Intraoperative intravenous lignocaine infusion was employed in this study to observe it effect on analgesia, hemodynamic stress response, and recovery profile in patients undergoing laparoscopic cholecystectomies.
METHODOLOGY AND RESULTS: This was a randomized placebo-controlled study with enrollment of 64 participants. The “L” group received preservative-free intravenous lignocaine 2% at 1.5 mg/kg bolus followed by continuous infusion at a rate of 1.5 mg/kg/h till skin closure. The “C” group received equal amounts of normal saline. No significant statistical difference was observed between the two groups with time to first analgesic, total analgesic consumption, and visual analog scale scores. No significant difference was seen with sedation, time to achieve modified Aldrete score, and time to return of bowel activity. Only significant difference in heart rate was observed in lignocaine group after intubation with no effects on mean arterial pressure.
CONCLUSION: Lignocaine infusion did not prove any added benefits in terms of postoperative analgesia, opioid requirements, and functional recovery after laparoscopic cholecystectomy. Hemodynamic stress response were better maintained in lignocaine group. Bolus dose of lignocaine may prove beneficial and equipotent as fentanyl.
Keywords: Analgesia, hemodynamic response, laparoscopic cholecystectomy, lignocaine, recovery
|How to cite this article:|
Kadni RR, Kumar G P, Joel C, Zachariah VK, Pushpavathi P, Narasimha AK. Influence of intraoperative lignocaine infusion on analgesia, stress response, and recovery profile in laparoscopic cholecystectomy: A randomized control study. Indian J Health Sci Biomed Res 2022;15:50-6
|How to cite this URL:|
Kadni RR, Kumar G P, Joel C, Zachariah VK, Pushpavathi P, Narasimha AK. Influence of intraoperative lignocaine infusion on analgesia, stress response, and recovery profile in laparoscopic cholecystectomy: A randomized control study. Indian J Health Sci Biomed Res [serial online] 2022 [cited 2022 May 22];15:50-6. Available from: https://www.ijournalhs.org/text.asp?2022/15/1/50/336292
| Introduction|| |
Laparoscopic surgeries are performed as daycare owing to the feasibility, safety, and reduced expenses for the patients., The postoperative pain in the first 24 h after laparoscopic procedure is of complex nature and high intensity.,, Growing evidence directs toward multimodal approaches and opioid-sparing drugs to accelerate recovery. Intravenous (IV) lidocaine has been shown to have analgesic, antihyperalgesic, and anti-inflammatory properties.,, Safety in the perioperative period and clear advantages, such as decreased intraoperative anesthetic requirements, lower pain scores, reduced postoperative analgesic requirements as well as faster return of bowel function and decreased length of hospital stay has been described.,,
In this study, we assessed the efficacy of intraoperative IV lignocaine infusion in patients undergoing laparoscopic cholecystectomy under general anesthesia. The primary objective was to measure the effect of lignocaine infusion on analgesia and hemodynamic stress response during intubation, incision, and extubation. Secondary objectives were to assess recovery profile in terms of emergence, time to achieve modified Aldrete score, sedation, return of bowel activity, and side effects in the perioperative period.
| Methodology|| |
This study was conducted in a tertiary multispecialty teaching hospital. It was a prospective, double-blind, randomized, placebo-controlled study. Ethical clearance was obtained from Bangalore Baptist Hospital's institutional ethical committee with reference no. ANA/125/2016 dated 19 24/05/2016. The study adheres to the applicable CONSORT guidelines [Figure 1].
Patients underwent a preoperative assessment and those fulfilling the inclusion criteria were included in the study after obtaining an informed written consent. Inclusion criteria were patients of both sex, aged 18–65 years, American Society of Anesthesiologists (ASA) status 1 and 2. Exclusion criteria were patients with body mass index (BMI) >35, uncontrolled hypertension or diabetes, on beta-blockers, cardiac concerns, hepatic or renal insufficiency, pregnant, breastfeeding or menstruating woman, alcohol or drug abuse, patients with chronic pain, and long-term use of analgesics or opioids, psychiatric disease with inability to comprehend pain assessment and allergic to local anesthetics. Study endpoint was conversion to open cholecystectomy due to any reason.
A fasting period of 6 h before surgery was advised. Premedication with tablets ranitidine 150 mg, metoclopramide 10 mg, and diazepam 10 mg were given 2 h before surgery. Patients were randomly divided into 2 groups, lignocaine group (L) and control group (C) by computer generated block randomization and allocation concealment method in sequentially numbered sealed envelopes. Total sample size was 64, with 32 in each group. The drug-filled syringes were prepared by an anesthetist not involved in the study. The patient, anesthetist conducting the case, and the observer were blinded to the study drugs.
Standard ASA monitoring with continuous electrocardiogram, pulse oximetry, capnography, noninvasive blood pressure, and temperature was done (Philips). Baseline parameters were recorded. The “L” group received preservative-free IV lignocaine 2% at 1.5 mg/kg bolus followed by continuous infusion at a rate of 1.5 mg/kg/h till skin closure. Using an infusion pump (Fresenius Kabi), the drug was given as 10 ml bolus and continuous infusion at a rate of 10 ml/h which constitutes the desired concentration during the preoxygenation. The “C” group received equal amounts of normal saline.
Patients were premedicated with IV dexamethasone 0.1 mg/kg and fentanyl 2 μg/kg. Anesthetic induction was done with IV propofol 1.5 mg/kg and atracurium 0.5 mg/kg for facilitating tracheal intubation. Anesthesia was maintained using isoflurane to maintain minimal alveolar concentration of 1 and O2:Air (50:50). Adequate muscle relaxation was achieved with 0.1 mg/kg atracurium given at appropriate intervals. Heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure, and mean blood pressure (MAP) will be recorded every 3 min in the first 15 min and later every 5 min throughout the surgery. Both groups received 1 g IV paracetamol at the time of skin incision. Tachycardia (HR >20% baseline) and hypertension (MAP > 20% of baseline) were treated with fentanyl 0.5 μg/kg to a maximum of total 5 μg/kg. IV esmolol 10 mg increments were planned for persistent tachycardia and hypertension once the maximum dose of fentanyl is reached intraoperatively. Bradycardia (HR <60 bpm) was to be treated with IV atropine (0.6 mg) and hypotension (defined as MAP <20% of baseline) with IV ephedrine 6 mg.
Local infiltration of port sites was done by the surgeon with 10 ml of 0.25% plain bupivacaine before skin closure. Once the skin closure was completed, the lignocaine or saline infusion will be stopped and inhalational agent was discontinued. Neuromuscular reversal (neostigmine 0.05 mg/kg and glycopyrrolate 0.01 mg/kg) was administered after confirming the return of spontaneous breathing. The patients were undisturbed except for continued verbal commands to open their eyes. Extubation was performed on return of protective reflexes with patient's ability to respond to simple verbal commands.
Time to first analgesic consumption, total analgesics consumed perioperatively, and visual analog scores were recorded to measure the analgesic role of the study drug.
All patients were evaluated for emergence agitation at extubation, using Richmond agitation sedation scale (RASS) 1-minimal or no response to noxious stimuli, 2-Arouse to physical stimuli but does not communicate, 3-difficult to arouse but awakens to verbal stimuli or gentle shaking, 4-calm and follow commands, 5-anxious or physically agitated and calms to verbal instructions, 6-requiring restraint and frequent verbal reminding of limits, 7-pulling at tracheal tube, trying to remove catheters or striking at staff. Emergence agitation will be defined as any score on the sedation agitation scale ≥5. Patients with agitation score of ≥6 were treated with IV midazolam 1 mg boluses.
After extubation, patients were transferred to the postanesthesia care unit (PACU). Postoperatively, pain was assessed using a visual analog scale (VAS) at 15 min, 30 min, 1, 2, 6, 12, and 24 h interval. Transfer to surgical ward was done when the patient achieves a modified Aldrete score ≥9. VAS score >3 in the PACU was treated with IV fentanyl 0.5 μg/kg up to a maximum of total 5 μg/kg and later with IV diclofenac 75 mg as 12th hourly interval. Intramuscular pethidine 50 mg was given as additional if required.
In the PACU Ramsay sedation score (RSS) (1-Awake, anxious, agitated or restless, 2-Awake, cooperative, oriented, tranquil, 3-Awake, responsive to commands only, 4-Asleep, brisk response to light glabellar tap or loud auditory stimulus, 5-Asleep, sluggish response to light glabellar tap or loud auditory stimulus, 6-Asleep, no response to light glabellar tap or loud auditory stimulus) will be assessed at 15 min, 30 min, 1 h, and 2 h postextubation. Time to discharge from recovery room in terms of modified Aldrete score was noted.
Return of bowel activity indicated by the time of passing of flatus as said by the patient will be recorded in the ward. Nausea and vomiting were monitored and treated with IV ondansetron 4 mg.
Quality control was done by entering data in excel sheets every week and 5% of data were rechecked every week to make it error free. The monitoring equipment used for monitoring patient's vital signs is frequently calibrated and checked by the hospital's maintenance department. The continuous variables were represented as means and standard deviations and categorical data as proportions. Student's t-test and Chi-square test were used to test statistically significant differences between two independent samples. Statistical software SSPC Inc. Released 2007. SPSS for Windows, Version 16.0. (Chicago, SPSS Inc.) was used for analysis. The level of statistical significance was set at P < 0.05 for all analyses.
| Results|| |
Patients demographics in terms of age, height, weight, BMI, and ASA status were comparable in both the groups [Table 1]. However, in terms of sex distribution, females were in significant numbers in the study and it was attributable to the fact that cholelithiasis most commonly affects female population. Operative durations were comparable in both groups and there was no conversion to open cholecystectomy.
The duration of the infusion was comparable in both the groups. The mean duration of lignocaine infusion was 134 min and that of saline infusion was 125 min with a P = 0.369.
The time duration for extubation after stopping lignocaine infusion was 7.5 min and after stopping saline infusion was 7.59 min with P = 0.9388.
The mean duration for first analgesic request was 246 min and after stopping saline infusion was 240 min with a P = 0.8902, with nil statistical significance [Figure 2].
Mean fentanyl consumption in the lignocaine group was 2.96 μg/kg and that in the saline group is 3.01 μg/kg with a P = 0.842. Mean doses of diclofenac consumed in the lignocaine group were 1.96 while in the saline group was 2.03 with a P = 0.162. Mean doses of pethidine consumed in lignocaine group were 0.31 and in saline group was 0.40 with a P = 0.471. The mean analgesics consumed in lignocaine group was less when compared to saline group, however, statistical difference was not attained [Table 2].
The VAS score did not show any statistical difference at any time intervals among the study groups up to 24 h postoperatively. The mean scores in the lignocaine group were lower than that in the saline group [Figure 3].
The mean HR at 5 min after intubation was 75 bpm in L group and 84 bpm in C group and was statistically significant with P = 0.002. At 1 min after incision, the mean HR was 75 bpm in L group and 83 bpm in C group which was statistically significant with a P value of 0.038. HR did not show any significance during the period of pneumoperitoneum in both groups. The mean HR in L group 1 min after extubation (HR23) was 97 bpm and that in C group was 105 bpm and a statistical difference of 0.044. Other HR variables did not show any statistically significant difference though there was a lesser mean HR in lignocaine group.
The mean arterial pressure did not show any statistical difference in the measured time intervals. However, the mean MAP among lignocaine group was lower than in the saline group [Table 3].
The mean RASS score in the L group was 4 ± 0.67 and that for C group was 4.28 ± 0.52 and with a P value of 0.066. RSAS score did not show any statistical difference among the two groups.
The RSS showed no statistical difference among the two groups up to 2 h after extubation. The mean value of RSS score in L group was higher than that in C group clinically.
No statistical difference was noted among time duration to reach modified Aldrete score and time to return of bowel activity.
Two incidences of nausea and vomiting were noted in patients among the L group which was treated with IV ondansetron 4 mg after which it subsided without any recurrence.
| Discussion|| |
The fact that pain after laparoscopic cholecystectomy is highly variable and characteristically involves several pain components with different pathophysiologic mechanisms. Perioperative side effects with the use of opioids may delay recovery and discharge or cause unanticipated readmission. Intraoperative use of opioids is associated with postoperative hyperalgesia and increased analgesic consumption.
It is therefore of great significance to relieve the pain and emotional stress and with reduced incidence of perioperative cardiovascular adverse reactions to allow early ambulation.
Mechanism of action of lignocaine centrally is by modifying neuronal responses in the spinal dorsal horn and peripherally by decreasing the inflammatory mediators. Sodium channel blockade and inhibition of G-protein coupled receptors and N-methyl-D-aspartate receptors are the mechanisms for lignocaine to achieve its analgesic action.,
Bisgaard et al. concluded that the overall intensity of pain after laparoscopic cholecystectomy is maximal within the first 4–8 h postoperatively with a rapid decline in the following 2–4 days. Groudine et al. studied IV lidocaine administration (3 mg/kg/h) in patients undergoing radical retropubic prostatectomy and concluded that lidocaine reduced the neural response to pain by blocking or inhibiting nerve conduction. The practical advantages of IV technique and clinical advantages of fewer opioid-related side effects and reduced opioid requirements in the perioperative period are the favorable points for the conduct of this study.
Yon et al. conclude that intraoperative lignocaine infusion was a good pre-emptive analgesic in patients undergoing subtotal gastrectomy. Lidocaine toxicity following IV infusion is more likely to manifest when its plasma concentration reaches 5 μg/mL. Doses between 1 and 2 mg/kg, administered as bolus followed by continuous infusion of 1.5 mg/kg/h correspond to plasma concentrations of 2 μg/ml. Our study was designed to give IV lidocaine intraoperatively with a bolus dose of 1.5 mg/kg followed by continuous infusion of 1.5 mg/kg/h in laparoscopic cholecystectomy taking into consideration to limit toxicity. The surgical procedure was standardized by the surgical team using the same technical principles and 4-trocar technique.
The mean first analgesic requirement time for the lignocaine group was 246.8 ± 187.2 min and that for the saline group was 240.2 ± 189.1 min with a P value-0.89. It was not statistically significant though the average time taken for the first analgesic request was slightly higher in lignocaine group. The postoperative pain was measured by a VAS and did not show any statistical difference between the two groups at any time intervals up to 24 h after extubation.
The mean total fentanyl, diclofenac, and pethidine requirement doses were not statistically significant in both groups. Frederic Martin et al. did not find any significant impact of lignocaine infusion on postoperative analgesia in patients undergoing total hip arthroplasty. Similarly, Insler et al. and Cepeda et al. did not observe opioid-sparing effect of lignocaine., In contrast, Lauwick et al. observed 36% reduction in postoperative fentanyl requirement in laparoscopic cholecystectomy patients. Groudine et al. and Kopper et al. noted opioid-sparing effect of lignocaine infusion in their studies.,
Baseline values of HR and SBP were comparable between the groups. HR at 5 min after intubation, 1 min after incision, and 1 min after extubation were statistically significant in the lignocaine group. These were comparable with study conducted by Dogan et al. who observed that lignocaine infusion suppressed the hemodynamics responses to painful stimulations as in our study. However, mean arterial pressure did not show any statistical difference in our study though the mean values at these intervals were lesser in the lignocaine group when compared to the saline group. Out of 64 patients, 5 developed hypotension, defined as two consecutive values <20% of baseline MAP, which was effectively treated with ephedrine.
Furthermore, RASS (P = 0.06), RSS (P > 0.05 at all measured intervals) and time to return of bowel activity (P = 0.49) showed no statistical difference. Ram et al. found a significant early return in bowel activity with IV lignocaine than with intraperitoneal instillation. There was no difference to attain a modified Aldrete score in our study among both groups. Dogan et al. observed delay with lignocaine group when compared to esmolol group.
Two patients in the lignocaine group developed nausea in the recovery room. None of the patients in the study group developed lignocaine toxicity. A meta-analysis from six randomized controlled trials concluded significant reduction in the incidence of nausea and vomiting, ileus and pruritus along with decreased pain scores and opioid consumption in lignocaine group.
We did not find any significant impact of IV lidocaine on postoperative analgesia or functional recovery after laparoscopic cholecystectomy. However, for this type of surgery, leading to moderate analgesic consumption and possibly limited central sensitization a larger sample size could point out significant opioid-sparing and antihyperalgesic effects of systemic lidocaine. Our results on analgesia could have been different if the infusion had been prolonged into the postoperative period. Lidocaine's analgesic properties might depend on lidocaine dose infused too, as demonstrated in animal study. It was shown that small doses suppress ectopic impulse generation in chronically injured peripheral nerve, whereas moderate doses suppress central sensitization and central neuronal hyperexcitability. However, large doses have general analgesic effect but can induce systemic toxicity. Lidocaine toxicity is correlated with its plasma concentration and the side effects become more likely at a plasma level of 5 μg/ml.
We monitored multiple parameters, which gives more information of the study drug.
In addition, laparoscopic surgeries are associated with raise intraocular pressures (IOPs), which can be hazardous in patients with glaucoma. IV lignocaine can play an significant role in reducing IOP by reducing the stress response to these surgeries and intubation/extubation procedures.
Limitations with our study were that we did not measure the plasma concentration of lidocaine which could contribute to the understanding of the pharmacokinetics of lidocaine and its systemic effects. The disease course, in duration, was not taken into account which could make a difference in pain perception due to central sensitization. Ocular manifestations we not a part of this study, monitoring the same could have been beneficial. Study on the effects of intermittent boluses of lignocaine than infusion could have added insight into the study. IV paracetamol and local infiltrations could have added to postoperative analgesia.
| Conclusion|| |
IV lignocaine infusion did not prove any added benefits in terms of postoperative analgesia, opioid requirements, and functional recovery after laparoscopic cholecystectomy. The hemodynamic stress response during intubation, incision, pneumoperitoneum, and extubation, were better maintained in patients who received lignocaine infusion. Lignocaine given as bolus dose was equipotent in action with bolus dose of fentanyl, as intraoperative requirement of fentanyl remained same in both groups.
- Department of Surgery, Bangalore Baptist Hospital, for their co-operation and teamwork
- Department of Community Health, Bangalore Baptist Hospital for their guidance and support.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3]
[Table 1], [Table 2], [Table 3]