|Year : 2016 | Volume
| Issue : 1 | Page : 29-33
Postoperative analgesia after laparoscopic cholecystectomy by preemptive use of intravenous paracetamol or ketorolac: A comparative study
Bhawana Rastogi, VP Singh, Kumkum Gupta, Manish Jain, Meetu Singh, Ivesh Singh
Department of Anaesthesiology and Critical Care, Subharti Medical College, Meerut, Uttar Pradesh, India
|Date of Web Publication||7-Jan-2016|
Dr. Bhawana Rastogi
Department of Anaesthesiology and Critical Care, Subharti Medical College, Meerut, Uttar Pradesh
Source of Support: None, Conflict of Interest: None
Background: Laparoscopic cholecystectomy is associated with postoperative pain due operative ports site and residual intraperitoneal gas CO 2 . Preemptive analgesia is one of the promising strategies of postoperative pain relief. The present study is undertaken to compare the efficacy of preemptive intravenous paracetamol versus ketorolac for post operative analgesia after laparoscopic cholecystectomy. Method: Ninety adult consented patients 18-58 yr of age, of either sex, of ASA grade I/II were randomized into two equal groups of 45 patients each. Patients of group I received infusion of paracetamol 1 g and group II received infusion of ketorolac 30 mg, 30 minutes before the induction of general anaesthesia. Postoperative pain was evaluated by standard 10 cm linear visual analogue scale at different time intervals. When VAS was more than 3 rescue analgesic 50 mg tramadol intravenously stat was given. Intraoperative hemodynamic and any side effects were also recorded for statistical analysis. Results: Demographic profile and hemodynamic parameters i.e intraoperative heart rate and mean arterial blood pressure were comparable in both the groups. Post operative VAS scores were persistently higher in paracetamol group with statistically significant difference (P value < 0.05). All 45 patients in paracetamol group and 8 patients in ketorolac group required rescue analgesic within 6 hrs of study time. Total tramadol consumption was much higher (2250 mg) in paracetamol group as compared to 400 mg in ketorolac group. Conclusion: Preemptive use of ketorolac exerted superior postoperative analgesia after laparoscopic cholecystectomy in comparison to paracetamol without any significant side effect.
Keywords: Intravenous ketorolac, intravenous paracetamol, laparoscopic cholecystectomy, postoperative analgesia, preemptive analgesia
|How to cite this article:|
Rastogi B, Singh V P, Gupta K, Jain M, Singh M, Singh I. Postoperative analgesia after laparoscopic cholecystectomy by preemptive use of intravenous paracetamol or ketorolac: A comparative study. Indian J Pain 2016;30:29-33
|How to cite this URL:|
Rastogi B, Singh V P, Gupta K, Jain M, Singh M, Singh I. Postoperative analgesia after laparoscopic cholecystectomy by preemptive use of intravenous paracetamol or ketorolac: A comparative study. Indian J Pain [serial online] 2016 [cited 2022 Dec 8];30:29-33. Available from: https://www.indianjpain.org/text.asp?2016/30/1/29/173460
| Introduction|| |
Laparoscopic cholecystectomy causes less postoperative pain and require lesser analgesic treatment as compared with open cholecystectomy. ,, As postoperative pain may be moderate to severe in some patient, they may require extensive analgesic treatment after laparoscopic cholecystectomy.
Incisions of the operative ports are the main cause of pain after laparoscopic cholecystectomy. Upper abdominal and shoulder tip pain after laparoscopy are probably caused by gas retained in the peritoneal cavity. Carbon dioxide is usually used to expand the abdomen to allow surgical visualization. Carbon dioxide may even take 2 days to get totally absorbed from the peritoneal cavity though it is more soluble than oxygen and nitrogen.
Preemptive analgesia is one of the upcoming strategies of pain management.  The definition of preemptive analgesia is controversial. It means an analgesic intervention before the surgical noxious stimulus arises, which has beneficial effects on the occurrence and intensity of postoperative pain.  The physical injury generates a complex stress response that contributes to the experience of postoperative pain. To cope the injury, the release of neurotransmitters, peptides, endocannabinoids, cytokines, and hormones occur, all of which operate interdependently through various nervous, endocrine, and immune processes.  Hence, preemptive analgesia partially decreases these influencing factors, which in turn, prevents the sensitizing effects of the surgical noxious stimuli.
Paracetamol is one of the most widely used drugs for the treatment of fever and pain. It is used perioperatively in oral, rectal, and parenteral formulations. It is still not confirm whether it acts peripherally and/or centrally and it acts on which analgesic pathway. Because of its efficacy, safety, lack of clinically significant drug interactions, and lack of the adverse effects associated with other analgesics, intravenous (IV) paracetamol is an important component of a multimodal analgesic treatment plan. 
Nonsteroidal anti-inflammatory (NSAIDs) drugs act by inhibiting the cyclooxygenase enzymes, and by decreasing the peripheral and central prostaglandin production. They not only reduce the inflammation that occurs due to tissue injury and decrease prostaglandin production but also attenuate the response of the peripheral and central components of the nervous system to noxious stimuli, leading to lesser peripheral, and central sensitization. These properties seem to make NSAIDs ideal drugs to use in a preemptive fashion.  Ketorolac acts by inhibiting both cyclooxygenase and lipooxygenase enzyme hence prevents synthesis of both prostaglandin and leukotrienes, and may enhance endogenous opioids release. Because of these properties of ketorolac is more potent than any other NSAIDs.
Pain after laparoscopic cholecystectomy is treated optimally with local anesthetic, paracetamol, NSAIDs, and opioids if required.  This study was performed to compare the efficacy and safety of preemptive use of IV paracetamol, and ketorolac for management of postoperative pain after laparoscopic cholecystectomy.
| Materials and Methods|| |
After approval from Institution Ethical Committee and written informed consent from all patients this prospective randomized double-blind clinical study was done on 90 patients of The American Society of Anesthesiologists grade I and II, aged 18-58 years with body weight of 50-60 kg of either sex, scheduled for elective laparoscopic cholecystectomy under general anesthesia. Patients with a history of allergy to study drugs, bleeding diathesis, chronic pulmonary disease, cardiovascular, renal disorder, and psychological disorder were excluded from the study after preoperative assessment.
Randomization was done by card method where a total of 90 cards, 45 in each group were prepared by another person who was blinded about the study. After recruitment, every patient was allowed to draw one card and grouped accordingly. Group I received IV paracetamol (1 g) and Group II received IV ketorolac (30 mg). A day before surgery all the patients were explained details of visual analogue scale (VAS) score. Tab.alprazolam 0.25 mg and tab.pantoprazol 40 mg were given orally night before surgery.
In the preoperative room, standard monitoring of heart rate, blood pressure, peripheral oxygen saturation, and electrocardiogram was commenced and an IV line was established and ringer lactate solution was started at the rate of 60-80 ml/h. All the study drugs were diluted in 100 ml normal saline and were infused over the period of 15 min, 30 min before induction of general anesthesia. After shifting to operation theater patients were premedicated intravenously with glycopyrrolate (0.004 mg/kg), midazolam (0.02 mg/kg) and fentanyl (2 μg/kg), and ondansetron 4 mg. After preoxygenation with 100% oxygen for 3 min, patients were induced with IV propofol (1%) in dose of 2 mg/kg followed by vecuronium 0.1 mg/kg to facilitate the laryngoscopy and tracheal intubation. Anesthesia was maintained with isoflurane, nitrous oxide 60% in oxygen, and vecuronium in incremental dosages of 0.02 mg/kg when train-of-four returned to 25%. The mean arterial blood pressure, heart rate, and SpO2 were recorded prior to induction, after induction and monitoring were continued at 15 min interval till the end of surgery and extubation. Extubation was done after a reversal of residual neuromuscular block with neostigmine (0.05 mg/kg) and glycopyrrolate (0.005 mg/kg) at the end of the surgery.
Patients were transferred to postanesthesia care unit to monitor hemodynamic parameters, postoperative pain, and any other adverse events such as nausea vomiting bleeding and abdominal pain for every 15 min till first 1 h, then every 1 hr till 6 h. Patients were evaluated for pain postoperatively using a standard 10 cm linear VAS. When VAS score was above 3 rescue analgesia of tramadol 50 mg IV was given to the patients. At the end of 6 h, the total amount of rescue analgesic, that is, tramadol required in each group was calculated.
Standard computer program computed that 90 patients were necessary for study keeping a dropout rate of 5%. This sample size would permit a type I error of alpha = 0.05, and type II error of beta = 0.2 (i.e. power of 80%).
On completion of the study, the data obtained were compiled in a tabulated manner as a mean ± standard deviation and analyzed by using Chi-square test and one-way ANOVA test. These statistical methods were applied with the help of Windows Excel 2007, Stat graphics Centurion 16 (Statpoint Technologies Inc, Warrenton, Virginia). P < 0.05 was taken as statistically significant.
| Results|| |
The study was successfully conducted on all 90 patients and there was no perioperative protocol deviation. All patients were cooperative with subsequent assessment of pain. The two treatment groups were comparable in regard to demographic profile and surgery time [Table 1].
Preoperatively, the baseline heart rate and mean blood pressure were comparable between the two treatment groups with no statistically significant difference. The heart rate and mean blood pressure did not show any significant difference between the groups after intubation, at 5 min, 15 min, 45 min, and 60 min, intraoperatively and at the end of surgical procedures [Table 2].
All patients were monitored for VAS scoring starting after arrival at PACU at every 15 min for 1 st h and hourly thereafter for 6 h. VAS scores were persistently high in paracetamol group till 6 h as compared ketorolac group. The VAS scores on the intergroup comparison at each time interval showed a significant difference as P < 0.05 at each point of time [Table 3].
|Table 3: Comparison of mean VAS scores of patients at each time interval|
Click here to view
The total number of patients requiring rescue analgesia were 45 (100%) in paracetamol group and 8 (17.7%) in ketorolac group within 6 h postoperatively (period of the study). This infer that majority of the patients (82.3%) in ketorolac group were pain free. Total tramadol consumption in paracetamol group was 2250 mg, while it was 400 mg in ketorolac group. Time to the first dose of analgesia was calculated from arrival to PACU to the time of requirement of rescue analgesia for the first time. The rescue analgesia was used much earlier in paracetamol group (91.88 ± 35.93) as compared to the ketorolac (240 ± 48.93) group [Table 4]. This duration of analgesia is highly significant statistically as P < 0.000. This also means that the duration of analgesia was longer with a single preemptive dose of ketorolac than paracetamol. Three patients in paracetamol group experienced nausea (6.66%), and seven patients (15.5%) had vomiting [Table 5].
| Discussion|| |
NSAIDS are helpful in management of the postoperative pain after laparoscopic cholecystectomy which is mainly visceral experienced due to rapid distension of peritoneum because of CO 2 insufflation which leads to traumatic traction of nerves and causes release of inflammatory mediators which cause pain.  This visceral pain occurs early in the postoperative period and its intensity decreases after first 24 h. NSAIDS are the best agents for pain relief after laparoscopic cholecystectomy may be because the pain in this surgery is mostly dependent on the release of inflammatory mediators.  Preemptive analgesia prevents the onset of the noxious stimulus and prevents central sensitization. Therefore, the concept of preemptive analgesia may have a role in reducing not only acute postoperative pain but also the chronic pain.
In the present prospective randomized double-blind study preemptive use of IV ketorolac was effective in reducing postoperative pain scores and amount of rescue analgesic in immediate postoperative period after laparoscopic cholecystectomy whereas IV paracetamol was not much effective in doing so. The difference in results in comparison to other studies may due to a different route, nature of surgery, or methodology problems.
Clinically, paracetamol has analgesic efficacy comparable to aspirin but it is less effective than other NSAIDs.  Md. Khan et al. studied the effect of preemptive dose of ketorolac, diclofenac and tramadol in laparoscopic cholecystectomy patients for postoperative pain and hemodynamic changes. They concluded that postoperative pain can be managed by preemptive use of diclofenac, ketorolac, and tramadol for the first 24 h with little or no supplementation of low dose IV pethidine. The analgesic efficacy of ketorolac and tramadol is same and better than diclofenac. There was no significant complication in using the drugs. 
Boccara et al. compared preemptive use of proparacetamol and ketoprofen for providing analgesia after laparoscopic cholecystectomy and concluded that preoperative administration of NSAIDS such as ketoprofen has better postoperative analgesia after laparoscopic cholecystectomy as compared to proparacetamol and postoperative use of both these drugs.  In another study Borisov et al. assessed the effect of single-dose of paracetamol for preemptive analgesia after abdominal surgery with perioperative epidural analgesia (epidural 0.75% ropivacaine) on 50 patients who underwent surgery for abdominal cancer lesions. They concluded that the use of 1 g of paracetamol as a single IV preemptive dose in abdominal surgery with perioperative epidural analgesia does not reduce the analgesic consumption and the intensity of pain in the postoperative period. 
Watcha et al. in their study summarized that the preoperative administration of oral ketorolac provides better postoperative analgesia than acetaminophen or placebo in children undergoing bilateral myringotomy. 
Hyllested et al. in qualitative review stated that NSAIDs were superior to paracetamol in two assay sensitive trials in orthopedic surgeries and in dental surgeries both in respect of pain scores and remedications. They also concluded that though the existing direct comparative studies shows NSAIDs are better than paracetamol in some surgeries ,e.g., dental but it is not same with other surgeries. According to them, paracetamol is a good alternative in high-risk patients as its side effects are negligible and it is more appropriate to combine both NSAIDs and paracetamol to get better analgesia. 
Arslan et al. conducted a study to determine the postoperative analgesic effects of preemptive IV paracetamol and the amount of reduction in tramadol consumption in 300 patients who received IV paracetamol 1 g 10 min before skin incision or IV paracetamol 1 g at the end of the operation and Group III (placebo) received 100 ml of saline solution 10 min before surgery. They concluded that preemptive IV paracetamol provided effective and reliable pain control after cholecystectomy surgeries and reduced postoperative pain scores, the need for and use of supplementary opioids, and increased the time to first request of analgesics. 
| Conclusion|| |
In summary preemptive use of single-dose of IV ketorolac can provide effective analgesia in early postoperative period with reduced consumption of rescue analgesic whereas single-dose of preemptive IV paracetamol alone could not produce effective analgesia in patients with laparoscopic cholecystectomy.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Dubois F, Icard P, Berthelot G, Levard H. Coelioscopic cholecystectomy. Preliminary report of 36 cases. Ann Surg 1990;211:60-2.
Joris J, Cigarini I, Legrand M, Jacquet N, De Groote D, Franchimont P, et al.
Metabolic and respiratory changes after cholecystectomy performed via laparotomy or laparoscopy. Br J Anaesth 1992;69:341-5.
Putensen-Himmer G, Putensen C, Lammer H, Lingnau W, Aigner F, Benzer H. Comparison of postoperative respiratory function after laparoscopy or open laparotomy for cholecystectomy. Anesthesiology 1992;77:675-80.
Grape S, Tramèr MR. Do we need preemptive analgesia for the treatment of postoperative pain? Best Pract Res Clin Anaesthesiol 2007;21:51-63.
Chapman CR, Tuckett RP, Song CW. Pain and stress in a systems perspective: Reciprocal neural, endocrine, and immune interactions. J Pain 2008;9:122-45.
Groudine S, Fossum S. Use of intravenous acetaminophen in the treatment of postoperative pain. J Perianesth Nurs 2011;26:74-80.
Dahl JB, Møiniche S. Pre-emptive analgesia. Br Med Bull 2004;71:13-27.
Aitkenhead AR, Smith G, Rowbotham DJ. Textbook of Anaesthesia: Churchill Livingstone; 2001.
Alexander JI. Pain after laparoscopy. Br J Anaesth 1997;79:369-78.
Graham GG, Davies MJ, Day RO, Mohamudally A, Scott KF. The modern pharmacology of paracetamol: Therapeutic actions, mechanism of action, metabolism, toxicity and recent pharmacological findings. Inflammopharmacology 2013;21:201-32.
Khan MR, Islam MZ, Hossain MS, Aziz L, Choudhury SS. Comparison of Pre-emptive use of diclofenac, ketorolac and tramadol for post-operative pain in laparoscopic cholecystectomy. J Bangladesh Soc Anaesthesiol 2007;20:24-9.
Boccara G, Chaumeron A, Pouzeratte Y, Mann C. The preoperative administration of ketoprofen improves analgesia after laparoscopic cholecystectomy in comparison with propacetamol or postoperative ketoprofen. Br J Anaesth 2005;94:347-51.
Borisov D, Levin A, Uvarov D, Sokolov A, Nedashkovsky E. An effect of non-opioid analgesics in addition to continuous thoracic epidural analgesia on postoperative pain in abdominal surgery: 14AP4-2. Eur J Anaesthesiol 2007;24:177.
Watcha MF, Ramirez-Ruiz M, White PF, Jones MB, Lagueruela RG, Terkonda RP. Perioperative effects of oral ketorolac and acetaminophen in children undergoing bilateral myringotomy. Can J Anaesth 1992;39:649-54.
Hyllested M, Jones S, Pedersen JL, Kehlet H. Comparative effect of paracetamol, NSAIDs or their combination in postoperative pain management: A qualitative review. Br J Anaesth 2002;88:199-214.
Arslan M, Celep B, Ciçek R, Kalender HÜ, Yilmaz H. Comparing the efficacy of preemptive intravenous paracetamol on the reducing effect of opioid usage in cholecystectomy. J Res Med Sci 2013;18:172-7.
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5]