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 Table of Contents  
ORIGINAL ARTICLE
Year : 2016  |  Volume : 3  |  Issue : 3  |  Page : 109-115

Combined gabapentin–celecoxib premedication as a part of multimodal analgesia for liposuction under monitored anesthesia care


1 Department of Anaesthesia and Intensive Care, Faculty of Medicine, Zagazig University, Zagazig, Egypt
2 Department of General Surgery, Faculty of Medicine, Zagazig University, Zagazig, Egypt

Date of Submission28-Sep-2015
Date of Acceptance19-Mar-2016
Date of Web Publication4-Nov-2016

Correspondence Address:
Ali M Elnabtity
Elnabtity, MD in Anesthesia and Intensive Care, Faculty of Medicine, Zagazig University, Saudi Arabia, Jeddah, Palesteen Street, PO Box: 2537, Jeddah, 21461
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/2356-9115.193409

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  Abstract 

Aim
The aim of this study was to evaluate the analgesic effect of gabapentin when combined with celecoxib on tumescent anesthesia during liposuction,aided by conscious i.v. sedation/analgesia.
Background
Multimodal analgesia is an essential part of monitored anesthesia care during liposuction. This prospective r andomized double-blinded controlled trial was designed to investigate the hypothesis that premedication with gabapentin and celecoxib can increase the analgesic efficacy of tumescent anesthesia and decrease the i.v. sedative/analgesic requirements during and after monitored anesthesia care for liposuction procedures.
Methods
Sixty-four patients (American Society of Anesthesiologist I and II) aged 18–50 years and undergoing liposuction were studied. The patients were randomly allocated into two groups: group I (control group, n = 31) and group II (gabapentin–celecoxib group, n = 33). Two hours before the procedure, patients of group I received oral placebo, and those of group II received oral gabapentin 1200 mg and celecoxib 400 mg. After standard premedication, sedation was maintained by a continuous infusion of propofol adjusted to achieve a Ramsay sedation scale score of 2–3. Intraoperative analgesia was maintained by incremental doses of i.v. ketamine 25–50 mg along with tumescent anesthesia at the operative site. Postoperative pain was managed by i.v. paracetamol at 1g/6 h. Meperidine 25–100 mg i.v. was administered as rescue analgesia. Intraoperative verbal rating scale scores for pain were assessed at 5 and 15 min and then every 15 min until the end of surgery. The total amount of intraoperative propofol and ketamine consumed was recorded. Postoperative visual analog scale for pain and Ramsay sedation score were assessed every 2 h and their worst values at intervals of 0–4, 4–8, and 8–12 h were considered for analysis. The total amount of meperidine consumed 12 h postoperatively and the time to first rescue analgesia request were recorded.
Results
Intraoperative pain scores at 90 and 120 min as well as the worst postoperative pain scores at intervals of 0–4 and 8–12 h were significantly lower in the gabapentin–celecoxib group. Ketamine (1.733 ± 0.398 vs. 01.996 ± 0.56mg/kg; P < 0.05) and meperidine (22.73 ± 33.29 vs. 83.87 ± 29.96mg; P < 0.001) consumptions were smaller and the time to first rescue analgesia (11.7 ± 1.13 vs. 8.18 ± 1.14 h; P < 0.001) was longer in the gabapentin–celecoxib group.
Conclusion
The current study concluded that premedication with gabapentin 1200 mg and celecoxib 400 mg augmented the analgesic effect of tumescent anesthesia during liposuction, aided by conscious i.v. sedation/analgesia.

Keywords: analgesia, celecoxib, gabapentin, liposuction, sedation, tumescent anesthesia


How to cite this article:
Abdelbaky Elnakera AM, Elnabtity AM, Elsadek AN. Combined gabapentin–celecoxib premedication as a part of multimodal analgesia for liposuction under monitored anesthesia care. Res Opin Anesth Intensive Care 2016;3:109-15

How to cite this URL:
Abdelbaky Elnakera AM, Elnabtity AM, Elsadek AN. Combined gabapentin–celecoxib premedication as a part of multimodal analgesia for liposuction under monitored anesthesia care. Res Opin Anesth Intensive Care [serial online] 2016 [cited 2020 Jun 4];3:109-15. Available from: http://www.roaic.eg.net/text.asp?2016/3/3/109/193409


  Introduction Top


Liposuction is considered one of the most common plastic surgeries performed nowadays [1]. Proper anesthetic management is essential for the success and safety of the procedure [2]. Conscious sedation and analgesia, as a part of monitored anesthesia care (MAC), along with tumescent anesthesia, can improve patient safety and satisfaction during the procedure as it eliminates the patient's anxiety and pain, avoids liposuction-related mortalities and complications reported under general anesthesia, and shortens the operative time, which is a risk factor for deep vein thrombosis formation, especially in this patient population. This approach can also enhance the surgeon's performance as it allows optimal tissue shaping [3]. Tumescent anesthesia is a mega-dose local anesthetic field block with lidocaine; it is ultra-dilute and epinephrinized, infiltrating the subcutaneous and periadipose tissue under hyperhydrostatic pressure [4]. Propofol–ketamine combination has been used as a balanced sedation/analgesia regimen, as when the two agents are combined they potentiate each other and attenuate their side effects [5],[6],[7]. Multimodal analgesia can be used to alleviate the pain during injection of the tumescent anesthesia and increase its analgesic efficacy as well [8]. Many clinical trials have evaluated the multimodal potential roles of gabapentin as a perioperative analgesic and anxiolytic drug [9],[10],[11],[12],[13],[14],[15],[16],[17],[18]. Multiple studies have shown the effectiveness of celecoxib in the management of postoperative pain whether given before or after surgery [19],[20],[21]. Preoperative combined administration of gabapentin 1200 mg and celecoxib 400 mg was recommended before subpectoral breast augmentation to decrease postoperative opioid requirements [22]. This prospective randomized double-blinded controlled trial aimed to test the hypothesis that patient premedication with gabapentin 1200 mg and celecoxib 400 mg can increase the analgesic efficacy of tumescent anesthesia and decrease the i.v. sedative/analgesic requirements during and after MAC for liposuction procedures.


  Patients and methods Top


After obtaining approval from the hospital board and informed consent from patients, this study was conducted at Altaiser International Hospital, Zagazig, from March to November 2009. Patients of American Society of Anesthesiologist class I–II undergoing liposuction were studied. Exclusion criteria were the following: age more than 50 years or less than 18 years; BMI greater than or equal to 40 kg/m2; operative time more than 120 min; smoking, or history of drug or alcohol abuse; presence of chronic pain syndromes; presence of clinically significant systemic (pulmonary, cardiac, diabetic, hypertensive, hepatic, and renal) diseases, uncontrolled thyroid disease, or coagulopathy; being on analgesic medications 48 h before surgery; concurrently taking anxiolytic or antidepressant medications; or known contraindication to any of the study's medications or techniques. Patients were instructed about the study plan, verbal rating scale (VRS), visual analog scale (VAS) for pain, Ramsay sedation score (RSS), and intraoperative and postoperative management protocols for pain during the preoperative visit. Patients were randomly assigned to two groups: group I and group II. Two hours before the procedure, patients of group I (control group) received oral placebo and patients of group II (gabapentin–celecoxib group) received oral gabapentin 1200 mg (Gabapentin; gaptin, 400 mg, Delta pharma, Egypt, gaptin; Delta Pharma) and celecoxib 400 mg (Celecoxib, Celebrex 200 mg , Pfizer, Cairo, Egypt) [12],[13],[14],[15],[16],[17],[18],[19],[20],[21],[22]. The study drugs were given to the patients by a supervising ward physician; all of the study procedures were performed by the same anesthetist and surgeon who were blinded to the patients’ group assignment. On arrival at the operating room, a 20 G i.v. line was inserted and continuous noninvasive monitoring of mean arterial pressure, heart rate, respiratory rate, and SpO2 was initiated (UT4000F Pro., Merlino, Italy; Samed Elettromedicali S.R.L.).

All patients were premedicated with 1 mg atropine and 2–4 mg midazolam i.v. They were given omeprazole 40 mg diluted in 100 ml saline 0.9% i.v. infusion over 15 min and ondansetron 8 mg i.v. over 5 min. Oxygen was administered at 4 l/min by means of a nasal cannula. After patient preparation, positioning, and draping under surgical antiseptic conditions, 2 ml of lidocaine 1% was given i.v., followed by i.v. infusion of propofol (10 mg/ml), which was started at 2.7 ml/kg/h (targeted to achieve 450 μg/kg/min) until the patient showed delayed response to verbal command (open your mouth; raise your right hand). At this point, ketamine 50 mg i.v. was administered and propofol infusion was reduced to 0.3 ml/kg/h (targeted to achieve 50 μg/kg/min) and manipulated (0.15–1 ml/kg/h) to achieve RSS level of 2–3 to allow patient's self-repositioning as indicated for the scheduled areas for liposuction (RSS 1 = anxious and/or agitated; RSS 2 = cooperative, oriented, and tranquil; RSS 3 = responds to commands only; RSS 4 = brisk response to light, glabellar tap, or loud auditory stimulus; RSS 5 = sluggish response to light, glabellar tap, or loud auditory stimulus; RSS 6 = no response) [23].

Local anesthetic was injected 2–3 min after ketamine administration into the subcutaneous tissue under high pressure of 300 mmHg at 250–400 ml/min. The tumescent anesthetic solution consisted of warm lactated Ringer's solution. Each liter contained 400 mg lidocaine (0.04%), 1 mg epinephrine (1: 1000 000), and sodium bicarbonate 10 mEq. The infused volume of tumescent anesthetic solution was 3–4 ml for each planned 1 ml of tissue aspirate. The maximum allowed dose of lidocaine is 35 mg/kg body weight [24]. After detumescence, liposuction was performed using special metal cannulas attached to a mechanical closed suction apparatus. Intraoperative assessment of pain was done using the five-point VRS (0 = no pain; 1 = mild pain; 2 = moderate pain; 3 = severe pain; and 4 = intolerable pain). Further supplemental i.v. ketamine 50 mg was administered only if two additional local anesthetic injections to the field failed to eliminate the patient's pain (VRS ≥2) [25],[26]. Patients were assessed for pain during the procedure using VRS at 5 and 15 min and then every 15 min until the end of the procedure. Total intraoperative propofol and ketamine consumptions during the procedure were recorded as mg/kg and considered for statistical analysis.

Episodes of unintentional deep sedation (RSS ≥5) with airway obstruction were recorded and treated by opening the airway by means of neck extension and lateral rotation, jaw thrust, oral airway insertion, or endotracheal intubation if indicated. During incidences of deep sedation, VRS was considered 0 until the patient's RSS returned to 2–3. Any incidence of hypoxemia (oxygen saturation ≤92%) was recorded and treated by increasing the FiO2, opening the airway, and through positive pressure ventilation as indicated. Hypotension, which was defined as a decrease in mean arterial pressure by ≥30%, was recorded and treated with i.v. fluids. Bradycardia was defined as heart rate less than 60 beats/min, and any such incidences were recorded and treated by supporting the airway/ventilation using i.v. atropine 0.5 mg, or i.v. ephedrine 3 mg increments if associated with hypotension. After the procedure, patients were nursed and monitored for symptoms and signs of fluid overload or lidocaine toxicity in the ward overnight. Postoperative assessment of pain was done using VAS, where VAS = 0 indicated no pain and VAS = 10 indicated the worst imaginable pain. Postoperative pain was managed using i.v. paracetamol (perfalgan) 1 g/6 h, and if the patient complained of pain (VAS≥4) i.v. meperidine 50 mg was administered as rescue analgesia. Patients’ RSS and VAS for pain at rest were recorded by a blinded observer nurse every 2 h, and their worst values during time intervals of 0–4, 4–8, and 8–12 h were considered for statistical analysis. The total meperidine consumption during the first postoperative 12 h and the time to the first postoperative rescue analgesic dose, measured from the time of administration of the study's drugs, were recorded. The incidence of postoperative nausea and vomiting (PONV) was noted and treated with i.v. ondansetron 8 mg (vomiting>2 episodes). Also the incidence of hallucination and shivering was recorded. On discharge, the patient's satisfaction with perioperative pain management was evaluated by means of a numerical rating score (NRS) where 0 = poor and 10 = excellent.

For a power of 80%, at 95% confidence interval and a difference in intraoperative ketamine dose of 0.3 mg/kg revealed in a previous pilot study, the calculated sample size was 30 for each group.

Statistical analysis

Qualitative variables were expressed as number and percentage, and comparison between two groups was carried out using the χ2-test and with the Fisher exact test when expected cells were less than five. Quantitative variables were expressed as mean and SD when data were parametric, and comparison between groups was done using the t-test. Nonparametric data were expressed as median and compared using the Mann–Whitney U-test. P values less than 0.05 were considered significant.


  Results Top


From 71 consecutive patients scheduled for liposuction during the study period, five patients were excluded either because they had a BMI greater than 40 kg/m2 or they were undergoing treatment with antidepressant drugs. Thus, 66 patients were enrolled in the study. Two patients, both in the gabapentin–celecoxib group, were subsequently excluded from the study because of an operative time greater than 120 min. Thus, data from 64 patients, 31 patients in the control group and 33 patients in the gabapentin–celecoxib group, were included and considered for analysis [Figure 1].
Figure 1: Flow diagram for patient distribution.

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There was no significant difference between the studied groups as regards age, sex, BMI, injected tumescent anesthetic volume, aspirated volume, operative time, and area to be subjected to liposuction (P > 0.05) [Table 1].
Table 1: Patient characteristics in the studied groups

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The median intraoperative VRS was similar in both groups for most of the measuring points except at 90 and 120 min intervals, at which it was significantly lower in the gabapentin–celecoxib group compared with the control group (P < 0.05) [Figure 2].
Figure 2: Intraoperative VAS in both groups.

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The worst postoperative median VAS was highly significantly lower in the gabapentin–celecoxib group compared with the control group at intervals of 0–4 and 8–12 h (P < 0.001), with no difference at 4–8 h [Figure 3]. The worst median RSS was similar in both groups at the intervals of 0–4 (median 2, range 2–3) and 4–8 h (median 2), but at 8–12 h it was significantly higher in the gabapentin–celecoxib group (median 2, range 2–3) than in the control group (median 2) (P < 0.05).
Figure 3: Postoperative VAS values in both groups.

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The average dose of administered intraoperative i.v. ketamine was significantly lower in the gabapentin–celecoxib group than in the control group (P < 0.05). However, the average intraoperative i.v. propofol dose showed no significant differences between the studied groups (P > 0.05). In the postoperative period, the average i.v. meperidine dose consumed by patients in the gabapentin–celecoxib group was highly statistically significantly lower compared with that of the control group (P < 0.001). Also, the time to first postoperative analgesic administration was highly significantly prolonged in the gabapentin–celecoxib group compared with the control group (P < 0.001). The average NRS for patient satisfaction with pain management was highly significantly higher in the gabapentin–celecoxib group than in the control group (P < 0.001) [Table 2].
Table 2: Intraoperative and postoperative analgesic requirements, time to first postoperative analgesia, and patients' NRS for satisfaction with pain management

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As regards complications, no statistical difference was found between the studied groups in terms of the incidence of episodes of unintentional deep sedation, PONV, hallucination, and shivering (P > 0.05) [Table 3]. The airway opening during deep sedation episodes, which were transient, was achieved by simple maneuvers without further need for endotracheal intubation.
Table 3: Intraoperative and postoperative complications

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  Discussion Top


The current study revealed that patient's premedication with gabapentin 1200 mg and celecoxib 400 mg, when given 2 h before liposuction performed under tumescent anesthesia aided by conscious sedation/analgesia under MAC, significantly reduced the intraoperative and 12 h postoperative i.v. analgesic requirements with significant prolongation in the time to first postoperative rescue analgesia. In the combination group, the intraoperative VRS values showed nonsignificant difference but the postoperative VAS values were significantly reduced when compared with those of the control group. These findings of improved analgesia were supported by the highly significant increase in NRS for patient satisfaction of pain management in the gabapentin–celecoxib group compared with the control group.

As acute postoperative pain has nociceptive, inflammatory, neurogenic, and visceral components, multimodal analgesic techniques using a number of analgesic drugs with different mechanisms of action are needed for adequate perioperative pain management [10].

Gabapentin is a structural analog of γ-aminobutyric acid. The nociceptive effect of gabapentin is a result of binding to the α2δ subunit of voltage-gated calcium channels, reducing the release of excitatory amino acids [12]. Gabapentin also is an antihyperalgesic that is thought to inhibit the dorsal horn N-methyl-d-aspartic acid receptors, reducing their hyperexcitability in response to tissue damage [9],[22]. In many clinical trials, preoperative gabapentin 1200 mg reduced preoperative anxiety, postoperative pain scores, and analgesic requirements [27],[28].

Celecoxib is a selective COX-2 inhibitor. When preoperatively administered it inhibits COX-2-mediated prostaglandin synthesis reducing nociceptive pain and preventing inflammation-induced hyperalgesia. Celecoxib is an effective alternative to both opioids and NSAIDs in the perioperative period. It offers analgesia without significant gastrointestinal toxicity or any adverse effects on platelet aggregation [19],[22]. Zemmel [29] concluded, in her systematic review, that perioperative administration of COX-2 inhibitors, as a part of multimodal pain management, improved postoperative analgesia in selected patients. Huang et al.[30] showed similar results after total knee arthroplasty.

Gilron et al.[31] demonstrated that postoperative administration of gabapentin–rofecoxib combination (1800/50 mg/day) improved pain associated with movement and decreased postoperative morphine consumption after abdominal hysterectomy. Parsa et al.[22] showed a reduction in postoperative pain and opioid requirements after subpectoral breast augmentation when using combined gabapentin 1200 mg and celecoxib 400 mg as premedication 30–60 min before the procedure. In agreement with the above results, our study demonstrated the beneficial effect of gabapentin–celecoxib combination in reducing the intraoperative and postoperative i.v. analgesic requirements. Similar findings were also demonstrated by Turan et al.[9], who investigated gabapentin 1200 mg given 1 h before nasal surgery as a part of multimodal analgesia including intraoperative local anesthetic infiltration and i.v. sedation analgesia with MAC, and by Turan et al.[32], who investigated gabapentin 1200 mg given 1 h before hand surgery to decrease the tourniquet-associated pain during i.v. regional anesthesia. Our study demonstrated similar VRS scores for pain in both groups at most of the intraoperative measuring points. However, Turan and colleagues[9],[32] showed significantly lower intraoperative VAS scores with gabapentin 1200 mg compared with controls. The difference may be due to the intraoperative use of VRS for pain assessment in the current study instead of VAS in Turan's studies.

Recart et al.[20] investigated celecoxib (400 mg) given 30–40 min before nasal surgery under general anesthesia. A slight reduction in intraoperative anesthetic/analgesic requirements and significant reductions in postoperative VAS for pain and i.v. opioid analgesic requirements were revealed, but unlike our finding the time to first postoperative rescue analgesia was unchanged. This may reflect the augmented analgesic effect of gabapentin–celecoxib combination in the current study.

The timing of gabapentin–celecoxib premedication 2 h before the procedure in the current study was to allow a maximal plasma concentration of the studied drugs on the start of surgical procedure [20],[33].

In the current study, no patient in any of the studied groups presented with hypotension and/or bradycardia and no difference was noted between groups regarding the incidence of intraoperative deep sedation episodes, PONV, shivering, and hallucination. Gilron et al.[31] revealed no increase in the incidence of postoperative complications on using gabapentin–rofecoxib combination. Most of the studies investigating the analgesic effect of gabapentin have reported no increase in the incidence of adverse effects, but a meta-analysis by Hurley and colleagues [12],[34] including 12 randomized controlled trials reported an increased incidence of postoperative sedation with gabapentin administration. Postoperative RSS in our study was higher in the gabapentin–celecoxib group at 8–12-h time interval without excessive sedation (RSS≥5).

One limitation of the current study was the use of RSS for guiding the intraoperative sedation instead of the more accurate bispectral index monitoring due to the unavailability of equipment. Other limitations were the small number of included patients and the short study period. Thus, further studies are needed to investigate the efficacy and safety of gabapentin–celecoxib combination in perioperative pain management.

The current study concluded that premedication with gabapentin 1200 and celecoxib 400 mg, given 2 h preoperatively, augmented the perioperative analgesic efficacy of tumescent anesthesia used during liposuction procedure, aided by conscious i.v. sedation/analgesia under MAC.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
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