|Year : 2014 | Volume
| Issue : 1 | Page : 45-50
Pregabalin/celecoxib versus midazolam/celecoxib as pre-emptive analgesia for minor day-case surgery
Sameh Mohamed Osman Abdelghany, Sherif Samir Wahba
Department of Anesthesiology, Intensive Care and Pain Management, Faculty of Medicine, Ain Shams University, Cairo, Egypt
|Date of Submission||28-May-2013|
|Date of Acceptance||01-Sep-2013|
|Date of Web Publication||31-May-2014|
Sameh Mohamed Osman Abdelghany
MD, Department of Anesthesiology, Intensive Care and Pain Management, Faculty of Medicine, Ain Shams University, Cairo
Source of Support: None, Conflict of Interest: None
Surgical stress is one of the most common causes of perioperative anxiety and postoperative pain. Pregabalin and celecoxib (P/C) have different mechanisms of analgesia demonstrated after a variety of surgical procedures. This study was designed to evaluate the efficacy, sedation, and postoperative pain control using combination of P/C as against midazolam and celecoxib (M/C) as a premedication.
Patients and methods
Sixty adult patients (20-60 years of age), ASA physical status I and II, of either sex scheduled to undergo elective minor day-case surgeries were randomly allocated into two groups of 30 patients each in this prospective study. Group I (P/C) received oral pregabalin (150 mg) and celecoxib (200 mg) 1 h before surgery, whereas group II (M/C) received oral midazolam (7.5 mg) and celecoxib (200 mg) 1 h before surgery. Preoperative sedation level was assessed using the Ramsay sedation scale. Intraoperative and postoperative analgesic consumption, the time to first analgesic requirement, and postoperative pain were recorded using visual analog scale. Adverse events were also recorded.
Preoperative sedation level and intraoperative hemodynamic parameters were significantly higher in the M/C group compared with the P/C group. Intraoperative and postoperative analgesic consumption were significantly higher in the M/C group, whereas the time for first analgesic requirement was significantly higher in the P/C group compared with the M/C group.
Premedication using combination of P/C in day-case surgery decreased analgesic consumption and had a good sedative level with limited adverse effects.
Keywords: Celecoxib, day-case surgery, pre-emptive analgesia, pregabalin
|How to cite this article:|
Abdelghany SM, Wahba SS. Pregabalin/celecoxib versus midazolam/celecoxib as pre-emptive analgesia for minor day-case surgery. Ain-Shams J Anaesthesiol 2014;7:45-50
|How to cite this URL:|
Abdelghany SM, Wahba SS. Pregabalin/celecoxib versus midazolam/celecoxib as pre-emptive analgesia for minor day-case surgery. Ain-Shams J Anaesthesiol [serial online] 2014 [cited 2019 Jul 15];7:45-50. Available from: http://www.asja.eg.net/text.asp?2014/7/1/45/128406
| Introduction|| |
Pain control after day-case surgery is still a major challenge . Although opioids play an important role in postoperative pain management, they are associated with many side effects . Pregabalin is a gabapentinoid compound that has been alleged to possess anxiolytic, analgesic, and anticonvulsant properties . Its usefulness has been established in the treatment of neuropathic pain . Therefore, it is claimed to be effective in preventing neuropathic component of acute nociceptive pain of surgery with opioid sparing and perioperative anxiety ameliorating effects . Although benzodiazepines are effective in reducing perioperative anxiety in the ambulatory setting, the anxiolytic effect is frequently accompanied by undesirable sedation. Furthermore, opioid-related postoperative nausea and vomiting, delayed recovery of bowel function, and adverse effect on other organ systems are well known .
Multimodal pain management is a well-known strategy to improve postoperative analgesic quality. For instance, cyclooxygenase-2-specific inhibitor and α2δ subunit of calcium channel ligands are two mechanistically different types of analgesics that has been proven efficient after a variety of surgical procedures ,. Although the effect of pregabalin on morphine consumption has been reported , its effect in combination with celecoxib is not clear.
Therefore, the overall objective of this study was to compare the combination of pregabalin and celecoxib (P/C) as against combination of midazolam and celecoxib (M/C) for pre-emptive analgesia and sedation in day-case surgery.
| Patients and methods|| |
After approval from our scientific and research committee (Ministry of Health of Kuwait Hospitals), written informed consent was obtained from 60 ASA physical status I-II patients (aged 20-60 years) undergoing elective day-case surgery between August 2011 and December 2012.
Exclusion criteria included known allergy to any of the study drugs, renal insufficiency, hepatic insufficiency, respiratory insufficiency, patients with sleep apnea syndrome, history of peptic ulcer, history of neurological disorders, pregnant patients, and patients receiving concomitant therapy with opioids or NSAIDs.
The patients were randomly allocated according to computer generated sequence into two equal groups (30 patients each): The P/C group and the M/C group. The patients were premedicated as follows:
Group I (P/C) received oral pregabalin (150 mg) capsule and oral celecoxib (200 mg) capsule 1 h before surgery.
Group II (M/C) received oral midazolam (7.5 mg) tablet and oral celecoxib (200 mg) capsule 1 h before surgery.
In the preoperative holding area, the sedation level was assessed using the Ramsay sedation scale: 1, patient is anxious and agitated or restless or both; 2, patient is cooperative, oriented, and tranquil; 3, patient responds to commands only; 4, patient exhibits brisk response to light glabellar tap or loud auditory stimulus; 5, patient exhibits a sluggish response to light glabellar tap or loud auditory stimulus; and 6, patient exhibits no response .
Before induction of anesthesia, all patients received standard monitoring (Datex-Ohmeda, USA) including noninvasive blood pressure, three-lead ECG, pulse oximetry, and capnography. Anesthesia was induced using fentanyl (1.5 μg/kg intravenously), propofol (2 mg/kg intravenously), and atracurium (0.5 mg/kg) to facilitate endotracheal intubation. Balanced anesthesia was maintained with an end-tidal sevoflurane (1.5-2%) and nitrous oxide (60%) in oxygen. Ventilatory parameters were adjusted to keep the EtCO 2 at a level of 32-35 mmHg.
Intraoperative analgesia was maintained by incremental doses of fentanyl (25 μg intravenously) and total intraoperative consumption was recorded. After recovery from anesthesia, residual neuromuscular block was reversed using neostigmine (40 μg/kg) with glycopyrrolate (5 μg/kg intravenously), and patients were extubated smoothly and transferred to the postanesthesia care unit. The level of postoperative pain was assessed using the visual analog scale (VAS), which is a 10-cm scale with 0 (no pain) and 10 (the worst pain). Postoperative analgesia was maintained by incremental doses of fentanyl (25 μg intravenously), if VAS was greater than 3.
Heart rate and mean arterial blood pressure (MAP) were recorded before induction of anesthesia (baseline) and every 10 min until the end of surgery. Intraoperative and total postoperative fentanyl consumption were recorded in addition to the time to first required analgesic dose. Patients' satisfaction was assessed 12 h postoperatively using four-point satisfaction scale: 1, poor; 2, fair; 3, good; and 4, excellent.
The primary outcome was to measure fentanyl consumption and the time to first request for fentanyl. The secondary outcome was to measure the level of sedation and hemodynamic response. Undesired effects were also recorded, such as nausea, vomiting, dizziness, somnolence, headache, and pruritus.
The required sample size was calculated using IBM© SPSS© SamplePower© (IBM© Corp., Armonk, New York, USA).
The primary outcome measure was fentanyl consumption. It was estimated that a sample size of 28 patients in each study group would have a power of 85% to detect a reduction in fentanyl consumption by one-third.
Data were revised for its completeness and consistency. Double data entry on SPSS program version 15 (Chicago, Illinois, USA) was performed. Quantitative data were summarized by mean value and SD or median value and interquartile range, whereas qualitative data were summarized by frequencies and percentages. Independent samples t-test, the Mann-Whitney U-test, and the χ2 -tests were used in the analysis of this study. A 'P value' of less than 0.05 was considered statistically significant.
| Results|| |
All patients completed the study successfully. Both groups, 30 patients each, were comparable with respect to patient's characteristics and duration of surgery as shown in [Table 1].
|Table 1: Patient's characteristics and duration of surgery in both groups|
Click here to view
The Ramsay sedation scale was significantly higher in the M/C group than in the P/C group [3 (2.7-4) vs. 1 (1-1.25), respectively, P < 0.01] as shown in [Table 2].
|Table 2: Comparison between the two studied groups with respect to the sedation score (Ramsay sedation scale) 1 h after medication|
Click here to view
At baseline evaluation, no significant statistical difference between the two groups was recorded with respect to the MAP, but subsequent readings at 10, 20, 30, 40, 50, and 60 min were significantly higher in the M/C group compared with the P/C group. The mean difference of the MAP in group P/C was 13.4, whereas the mean difference of MAP in the M/C group was only 2.8; hence, the effect of M/C combination is only 20% of the total effect of P/C combination (0.2) as shown in [Table 3].
|Table 3: Comparison between the two studied groups with respect to the mean arterial pressure preoperative and intraoperative|
Click here to view
The result showed no statistically significant difference between the two groups with respect to the mean pulse rate [Table 4] at baseline evaluation (preoperatively). However, there was a higher mean pulse rate at 10, 20, 30, 40, 50, and 60 min in the M/C group compared with the P/C group and the difference was highly significant statistically.
|Table 4: Comparison between the two studied groups with respect to the mean pulse rate preoperative and intraoperative|
Click here to view
The mean difference in the P/C group was 13.6, whereas the mean difference in the M/C group was 7.8; hence, the effect of M/C combination on the pulse rate is only 50% of the effect of P/C combination (0.5).
With respect to the VAS score [Table 5], there was a higher median VAS score among patients in the M/C group compared with the P/C group and the difference was highly significant statistically (P < 0.01).
|Table 5: Comparison between the two studied groups with respect to the visual analog scale scores at baseline, immediate postoperative, and at 1, 2, 4, 6, 8, 10, and 12 h postoperatively|
Click here to view
Intraoperative fentanyl consumption was significantly higher in the M/C group compared with the P/C group [160.8 (45.3) vs. 122 (26.4), respectively, P < 0.01] as shown in [Table 6] (1.3 times higher dosage). Higher mean time until first analgesic dose was achieved among patients in the P/C group and the difference was highly significant statistically [361 (37.9) vs. 67.7 (13), respectively, P < 0.01]. Meanwhile, a higher mean dosage of postoperative analgesic consumption was achieved among the M/C group compared with the P/C group [218.3 (55.8) vs. 125 (24.8), respectively] and the difference was highly significant statistically (1.7 times higher the mean dosage, P < 0.01) as shown in [Table 6].
|Table 6: Comparison between the two studied groups withrespect to the analgesics consumption of fentanyl injection doses intraoperatively, time to first analgesic dose postoperatively, and postoperative analgesic administration dose|
Click here to view
The two groups were comparable with respect to the occurrence of undesirable side effects (P > 0.05) as shown in [Table 7]. None of the patients in the two groups had urinary retention, vertigo, or visual disturbances as an adverse event.
|Table 7: Comparison between the occurrences of adverse events between the two studied groups|
Click here to view
In comparison between the two studied groups with respect to patients satisfaction [Table 8], there was a higher percentage of excellent evaluation in the P/C group, 63.3% compared with 33.3% among the M/C group. In addition, a higher percentage of fair and poor satisfactions were achieved among the M/C group compared with the P/C group and the difference was significant statistically.
|Table 8: Comparison between the two groups with respect to patient's satisfaction of the drug|
Click here to view
| Discussion|| |
Preoperative anxiety and postoperative pain control are common anesthetic challenges. Managing preoperative anxiety and postoperative pain inadequately is reflected directly on the stress response of surgery, which is directly proportional to patients' hemodynamics and reflected negatively on the perioperative course. Drugs with anxiolytic and analgesic properties that suits day-case surgery are scarce.
The present study evaluated two groups of patients undergoing minor elective day-case surgery who were orally premedicated with either P/C or M/C. The study showed that oral premedication with a single dose of P/C was effective in reducing preoperative anxiety and intraoperative and postoperative analgesic consumption.
Pregabalin as well has been successfully used to improve pain control, and the efficacy of gabapentin combination with morphine has been evaluated for neuropathic pain control .
In this study, a desirable sedation level was achieved in the P/C group, whereas a deep sedation level with profound somnolence was found among the M/C group. In support to this finding, Rickels et al.  found that the use of pregabalin in patients with generalized anxiety was significantly more effective than the use of benzodiazepine in improving anxiety symptoms.
The current study showed that the intraoperative hemodynamic variables were significantly higher in the M/C group compared with the P/C group and the mean difference of MAP (compared with preoperative baseline) in the P/C group was 13.4, whereas the mean difference in the M/C group was only 2.8; hence, the effect of M/C combination on the blood pressure values was only 20% of the total effect of P/C combination.
In agreement with this study, which revealed increase in the time to first analgesic dosage and decreased analgesic consumption in the P/C group compared with the M/C group, White et al.  administered pregabalin twice daily and found superior analgesia and lower opioid consumption throughout the study.
Another study conducted by Reuben et al.  evaluated the analgesic efficacy of P/C before and after spinal fusion surgery and concluded that P/C reduced postoperative opioid usage compared with a placebo.
This combination seems essential to obtain a satisfactory result when dealing with pain control of surgical origin. For instance, in one trial , a single preoperative dose of pregabalin did not result in any analgesic benefit.
In addition, Peach et al.  reported that pregabalin in a single preoperative dose (100 mg) was ineffective in reduction of postoperative pain or improving the recovery after minor surgery involving only the uterus.
In another recent study, Peng et al.  studied pregabalin preoperatively at a dose of 50 and 75 mg and concluded that perioperative administration of pregabalin (75 mg) provided limited analgesic benefit during the postoperative period.
This result may be contributed to the smaller dose used compared with the dose used in the current study (150 mg). Furthermore, pregabalin is rapidly and extensively absorbed after oral dose, with maximal plasma concentration occurring 1 h after oral intake . Other factors that improve the outcome include choice of multimodal analgesic regimen and time of drug administration.
The results of the current study were in agreement with those achieved by Gupta et al. , who studied the preoperative administration of pregabalin (150 mg) as against clonidine (200 μg); their results showed that pregabalin and clonidine proved to have sedative and anxiolytic effects as oral premedicants and decreased the need of intraoperative analgesic drug requirement. In another study , two different doses of oral pregabalin (75 and 150 mg) were evaluated with respect to pressor response of airway instrumentation. It was concluded that pregabalin as a premedication has an adequate sedative effect and attenuated the hemodynamic pressor to intubation response in a dose-related manner.
The present study showed no statistically significant difference between the two studied groups with respect to the adverse events; however, a higher number of patients had dizziness in the P/C group, whereas a higher number of patients had somnolence and headache in the M/C group. Similarly, pregabalin in combination with celecoxib was studied by Romano et al.  and reported that five of the 36 patients had nausea and dizziness but did not require treatment discontinuation. In contrast, the clinical trial conducted by Jokela et al.  observed a decrease in oxycodone consumption with perioperative administration of pregabalin (300 mg) before and after laparoscopic hysterectomy, but it was associated with an increased incidence of adverse effects. This may be attributed to the higher dose of pregabalin used in comparison with the dose of pregabalin used in the current study.
There are some limitations in our study. First, pregabalin was given only 1 h before induction of anesthesia, which did not allow adequate assessment of its anxiolytic action. However, its absorption takes less than 1 h and its bioavailability exceeds 90% fortunately ,,. Second, a small and single dose of pregabalin (150 mg) was given, but, as the study was conducted on day-case surgery, authors were aiming to reduce the side effects of the drug.
| Conclusion|| |
The use of pregabalin (150 mg) in combination with celecoxib (200 mg) as a premedication for minor day-case surgeries improved preoperative sedative level and decreased intraoperative and postoperative analgesic consumption with limited adverse effects.
| Acknowledgements|| |
Conflicts of interest
| References|| |
|1.||Apfelbaum JL, Chen C, Mehta SS, Gan TJ. Postoperative pain experience: Results from a national survey suggest postoperative pain continues to be undermanaged. Anesth Analg 2003; 97:534-540. |
|2.||Kehlet H, Wilmore DW. Multimodal strategies to improve surgical outcome. Am J Surg 2002; 183:630-641. |
|3.||Paul F, Burcu T, Jimmie T, Kevin K. The effect of pregabalin on preoperative anxiety and sedation levels: A dose-ranging study. Anesth Analg 2009; 108:1140-1145. |
|4.||Lesser H, Sharma U, LaMoreaux L, Poole RM. Pregabalin relieves symptoms of painful diabetic neuropathy - a randomized controlled trial. Neurology 2004; 63:2104-2110. |
|5.||Pande AC, Feltner DE, Jefferson JW, Davidson JR, Pollack M, Stein MB et al. Efficacy of the novel anxiolytic pregabalin in social anxiety disorder: A placebo-controlled, multicenter study. J Clin Psychopharmacol 2004; 24:141-149. |
|6.||White PF, Kehlet H. Improving pain management: Are we jumping from the frying pain into the fire? Anesth Analg 2007; 105:10-12. |
|7.||Gilron I, Orr E, Tu D, O′Neill JP, Zamora JE, Bell AC. A placebo-controlled randomized clinical trial of perioperative administration of gabapentin, rofecoxib and their combination for spontaneous and movement evoked pain after abdominal hysterectomy. Pain 2005; 113:191-200. |
|8.||Dahl JB, Mathiesen O, Moniche S. Protective premedication: An option with gabapentin and related drugs? A review of gabapentin and pregabalin in the treatment of postoperative pain. Acta Anaesthesiol Scand 2004; 48:1130-1136. |
|9.||Ittichaikulthol W, Virankabutra T, Kunopart M, Khamhom W, Putarawuthichai P, Rungphet S. Effects of pregabalin on postoperative morphine consumption and pain after abdominal hysterectomy with/without salpingo-oophorectomy: A randomized, double-blind trial. J Med Assoc Thai 2009; 92:1318-1323. |
|10.||Ramsay MA, Savege TM, Simpson BR, Goodwin R. Controlled sedation with alphaxalone-alphadolone. Br Med J 1974; 2:656-659. |
|11.||Gilron I, Bailey JM, Tu D, Holden RR, Weaver DF, Houlden RL. Morphine, gabapentin, or their combination for neuropathic pain. N Engl J Med 2005; 352:1324-1334. |
|12.||Rickels K, Pollack MH, Feltner DE, Lydiard RB, Zimbroff DL, Bielski RJ, et al. Pregabalin for treatment of generalized anxiety disorder: A 4-week, multicenter, double-blind, placebo-controlled trial of pregabalin and alprazolam. Arch Gen Psychiatry 2005; 62:1022-1030. |
|13.||White PF, Tufanogullari B, Taylor J, Klein K. The effect of pregabalin on preoperative anxiety and sedation levels: A dose-ranging study. Anesth Analg 2009; 108:1140-1145. |
|14.||Reuben SS, Buvanendran A, Kroin JS, Raghunathan K. The analgesic efficacy of celecoxib, pregabalin, and their combination for spinal fusion surgery. Anesth Analg 2006; 103:1271-1277. |
|15.||Jokela R, Ahonen J, Tallgren M, Haanpää M, Korttila K. Premedication with pregabalin 75 or 150 mg with ibuprofen to control pain after day-case gynaecological laparoscopic surgery. Br J Anaesth 2008; 100:834-840. |
|16.||Paech MJ, Goy R, Chua S, Scott K, Christmas T, Doherty DA. A randomized, placebo-controlled trial of preoperative oral pregabalin for postoperative pain relief after minor gynecological surgery. Anesth Analg 2007; 105:1449-1453. |
|17.||Peng PWH, Li C, Farcos E, Haley A, Wrong W, et al. Use of low dose pregabalin in patients undergoing laparoscopic cholecystectomy. Br J Anaesth 2010; 105:155-161. |
|18.||Ben-Menachem E. Pregabalin pharmacology and its relevance to clinical practice. Epilepsia 2004; 45:13-18. |
|19.||Gupta K, Sharma D, Gupta PK. Oral premedication with pregabalin or clonidine for hemodynamic stability during laryngoscopy and laparoscopic cholecystectomy: A comparative evaluation. Saudi J Anaesth 2011; 5:179-184. |
|20.||Rastogi B, Gupta K, Gupta PK, Agarwal S, Jain M, Chauhan H. Oral pregabalin premedication for attenuation of hemodynamic pressor response of airway instrumentation during general anesthesia: A dose response study. Indian J Anaesth 2012; 56:49-54. |
|21.||Romanò CL, Romanò D, Bonora C, Mineo G. Pregabalin, celecoxib, and their combination for treatment of chronic low back pain. J Orthop Traumatol 2009; 10:185-191. |
|22.||Jokela R, Ahonen J, Tallgren M, Haanpää M, Korttila K. A randomized controlled trial of perioperative administration of pregabalin for pain after laparoscopic hysterectomy. Pain 2008; 134:106-112. |
|23.||Randinitis EJ, Posvar EL, Alvey CW, Sedman AJ, Cook JA, Bockbrader HN. Pharmacokinetics of pregabalin in subjects with various degrees of renal function. J Clin Pharmacol 2003; 43:277-283. |
|24.||Gajraj NM. Pregabalin: Its pharmacology and use in pain management. Anesth Analg 2007; 105:1805-1815. |
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6], [Table 7], [Table 8]