|Year : 2019 | Volume
| Issue : 2 | Page : 228-233
Intraperitoneal instillation of lornoxicam–levobupivacaine versus tramadol–levobupivacaine in patients undergoing laparoscopic cholecystectomy under general anesthesia
Salwa M.S Hayes1, Emad El Hefnawy1, Waleed A Askar2, Lucy A.M Suliman3
1 Department of Anesthesia and Intensive Care, Faculty of Medicine, Mansoura University, Mansoura, Egypt
2 Department of Surgery, Faculty of Medicine, Mansoura University, Mansoura, Egypt
3 Department of Chest Medicine, Faculty of Medicine, Mansoura University, Mansoura, Egypt
|Date of Submission||31-Jan-2019|
|Date of Acceptance||02-Feb-2019|
|Date of Web Publication||12-Jun-2019|
Salwa M.S Hayes
Source of Support: None, Conflict of Interest: None
Background Intraperitoneal local anesthetic administration is used for reducing postoperative pain after laparoscopic surgery, this study aimed to compare intraperitoneal instillation of lornoxicam–levobupivacaine versus tramadol–levobupivacaine on the quality of postoperative analgesia for elective laparoscopic cholecystectomy.
Patients and methods After ethical approval, 90 (30/group) patients scheduled for elective laparoscopic cholecystectomy were randomly allocated to receive intraperitoneal instillation of either 25 ml of normal saline for patients in group S, 20 ml of levobupivacaine 0.5% combined with 5 ml of lornoxicam (16 mg) for patients in group L or to receive 20 ml of levobupivacaine 0.5% combined with 5 ml of tramadol (100 mg) for patients in group T. Postoperative pain-free period, visual analog pain scores, pulmonary functions and cumulative fentanyl consumption were recorded.
Results Postoperative pain-free period showed significantly longer duration in group L and group T in comparison to group S with 6.86 h in group L and 6.90 h in group T versus 1.33 h in group S at 95% confidence interval, also total fentanyl consumption decreased in group L and group T in comparison to group S. Pulmonary functions were decreased in all groups but with less decrease in group L and group T in comparison to group S.
Conclusion Addition of either lornoxicam or tramadol provided safe, effective, less affection of pulmonary functions and good quality of analgesia when added to levobupivacaine without any significant differences between both groups for intraperitoneal administration.
Keywords: intraperitoneal instillation, laparoscopic cholecystectomy, levobupivacaine, lornoxicam
|How to cite this article:|
Hayes SM, El Hefnawy E, Askar WA, Suliman LA. Intraperitoneal instillation of lornoxicam–levobupivacaine versus tramadol–levobupivacaine in patients undergoing laparoscopic cholecystectomy under general anesthesia. Res Opin Anesth Intensive Care 2019;6:228-33
|How to cite this URL:|
Hayes SM, El Hefnawy E, Askar WA, Suliman LA. Intraperitoneal instillation of lornoxicam–levobupivacaine versus tramadol–levobupivacaine in patients undergoing laparoscopic cholecystectomy under general anesthesia. Res Opin Anesth Intensive Care [serial online] 2019 [cited 2019 Oct 14];6:228-33. Available from: http://www.roaic.eg.net/text.asp?2019/6/2/228/260138
| Introduction|| |
Laparoscopic cholecystectomy considered the more common surgical procedure than the conventional laparotomy surgery for cholecystectomy because it has the advantages of more rapid return to normal activity, with early discharge and minimal effects on pulmonary functions, however, the most common disadvantage is the presence of pain during the first postoperative day that may predispose to chronic pain .
Intraperitoneal administration of local anesthetic may be used during or after laparoscopic cholecystectomy surgery for reducing postoperative pain . Different drugs may be added as an adjuvant to the local anesthetic to improve the quality of analgesia ,.
Tramadol was used as an adjuvant to local anesthetic, it is characterized by its central analgesic effects due to affinity for m-opioid, monoaminergic receptors agonistic activities and inhibition of serotonin and norepinephrine neuronal reuptake, also it is characterized by its limited adverse effects when added to local anesthetic for nerve blocks, subcutaneously or intra-articularly ,,.
Lornoxicam is considered as a potent NSAIDs drug that having potent anti-inflammatory and analgesic effects. Lornoxicam has been shown to be at least as effective as comparative NSAIDs and more effective than 10 mg morphine when used at doses more than or equal to 8 mg to control pain also lornoxicam combines the high therapeutic potency of oxicams with an improved gastrointestinal toxicity profile ,. It is safe and effective for reducing postoperative analgesic consumption, intravenous lornoxicam has a similar analgesic effect and less adverse effects in comparison to tramadol for postoperative pain management , this benefit could be used to achieve analgesia after laparoscopic cholecystectomy.
We hypothesized that intraperitoneal administration of lornoxicam with local anesthetic could be used in improving postoperative pain after laparoscopic cholecystectomy under general anesthesia. We evaluated the efficacy of intraperitoneal instillation of lornoxicam–levobupivacaine in comparison to tramadol–levobupivacaine on the postoperative pain-free period as a primary outcome, quality of analgesia, total postoperative opioid consumption and pulmonary functions as a secondary outcome following laparoscopic cholecystectomy under general anesthesia.
| Patients and methods|| |
After approval of Local Ethical Committee of Mansoura University, Faculty of Medicine (with referral number R/15.05.30), this prospective, randomized clinical trial was performed at Mansoura University Gastroenterology Center after taking written informed consent on 90 patients aged from 20 to 60 years of either sex of American Society of Anesthesiologist physical status grade I or II, and scheduled for elective laparoscopic cholecystectomy surgery under general anesthesia.
Exclusion criteria included patients with allergy to any of drugs used, cardiac, pulmonary, hepatic, renal patient, with contraindication for NSAIDs, clotting or bleeding disorders, diabetes mellitus, morbid obesity, pregnancy, and those receiving other NSAIDs a day before surgery.
Preoperative instructions to patients for visual analog scale (VAS) was done by an investigator who was not involved in the study to assess the severity of postoperative pain where 0 mm for no pain while 100 mm for worst imaginable pain. Before induction of anesthesia, the syringes containing study solutions were prepared and were masked by identical opaque cover sheets by one anesthesiologist not involved in the study protocol. Anesthetic management was standardized and anesthesia was induced by another anesthesiologist not involved in the study with instructions to avoid using local anesthetics, induction was done with fentanyl 2 μg/kg, propofol 2 mg/kg and atracurium 0.5 mg/kg for endotracheal tube insertion, maintenance of anesthesia was achieved with one minimum alveolar concentration isoflurane in 50% oxygen in air. Atracurium 0.2 mg/kg was given according to the decision of anesthesiologist with adjustment of ventilation to keep end-tidal carbon dioxide (ETCO2) around 35 mmHg. the minimum alveolar concentration of isoflurane was increased and additional intraoperative fentanyl 1 μg/kg was given if the heart rate increased or mean blood pressure increased within 20% of their baseline values. Patient monitoring included heart rate, noninvasive blood pressure, and oxygen saturation before induction of anesthesia (baseline) and every 10 min up to the end of surgery. ETCO2 was recorded every 10 min after intubation until the end of surgery. Intra-abdominal pressure was maintained between 10 and 12 mmHg. At the end of surgery allocation of patients were done randomly into three groups (30 patients for each) using numbered closed sealed envelopes containing randomization code in which group S received intraperitoneal instillation of 25 ml of normal saline while group L received intraperitoneal instillation 20 ml of levobupivacaine 0.5% combined with 5 ml of lornoxicam (16 mg) and group T received intraperitoneal instillation 20 ml of levobupivacaine 0.5% combined with 5 ml of tramadol (100 mg). Intraperitoneal instillation was done in the Trendelenburg position, the study or saline solutions were intraperitoneally instilled at the site of surgery by the surgeon through a catheter under the direct laparoscopic vision and allow them to diffuse through the hepatodiaphragmatic space.
Isoflurane was discontinued and intravenous antiemetic prophylaxis with ondansetron 0.1 mg/kg was given and the residual neuromuscular block was antagonized using neostigmine 40 μg/kg and atropine 20 μg/kg and after removal of endotracheal tube, patients were shifted to the postanesthesia care unit. Duration of surgical procedure and anesthesia time were recorded.
In the postanesthesia care unit, patients were continued for monitoring of the heart rate, oxygen saturation and noninvasive blood pressure for 1 h postoperative. Patients were discharged to the surgical ward if they achieved a score of 10 at the modified Aldrete score. Postoperative pain assessment was done using VAS which was used for evaluation of pain at rest and during movement (rising from supine to the sitting position) at 0.5, 1, 2, 4, 12, 24 h postoperatively.
Postoperative analgesia was achieved using intravenous ketorolac 30 mg/dose every 8 h. After 30 min of ketorolac injection, intravenous fentanyl 0.5 μg/kg was available as rescue analgesia if VAS continued to be more than 30 mm. Fentanyl injection could be repeated. The cumulative fentanyl consumption during the first 24 h postoperatively and time for the first request of analgesia were recorded.
Spirometric values included forced expiratory volume in 1 s (FEV1) and Forced vital capacity (FVC) were recorded via portable spirometry (MIR; Spirolab II, Italy) preoperatively, 4 and 12 h postoperative, the presence of complications as nausea, vomiting, gastritis, reflux esophagitis, headache, or bronchospasm were recorded. Data collection and patients monitoring were done by an independent investigator.
Analysis of data was done by using excel program for figures and SPSS (for IBM) program statistical package for the social sciences, version 22. Description of the data expressed as mean±SD for quantitative data while for qualitative data the frequency and proportion were used. Normality of distribution was tested by Kolmogorov–Smirnov test and Shapiro–Walk test and all continuous data revealed to be parametric and normally distributed, data analysis was done to test statistical significant difference between groups. One way analysis of variance was used for a quantitative date to compare between more than two groups followed by post-hoc test and for comparison between two groups independent sample t-test was used. χ2-Test was used for qualitative variables. A P value of less than 0.05 was considered significant.
In this clinical trial the G Power (3.0.10) analysis program was used with time to take first analgesic request as the primary variant and assuming 0.05 type I error protection with effect size convention of 0.80 so the total sample size will be 84 patients and to protect against drop out cases we added six cases, so the total number was 90 cases with 30 patients in each group.
| Results|| |
Ninety patients of both sex aged between 20 and 60 years completed this randomized clinical trial with 30 patients in each group. As regards the demographic data, the studied groups were comparable and the surgical duration and duration of anesthesia among the studied groups showed the insignificant difference ([Table 1]). As regards the perioperative hemodynamic changes the studied groups showed insignificant differences throughout the study, similarly, perioperative oxygen saturation and ETCO2 showed insignificant differences among the studied groups.
|Table 1 Patient characteristics, duration of surgery (min), and duration of anesthesia (min)|
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Meanwhile, according to postoperative pain assessment using VAS, the 95% confidence interval (CI) for mean difference for VAS at rest and during movement showed significantly decreased in group L and group T in comparison to group S throughout the study period (with P=0.000) while there were no significant differences between group L and group T ([Figure 1] and [Figure 2]). As regard the duration to take the first postoperative rescue analgesic request, CI for mean difference showed significantly longer duration of effective analgesia in group L 6.86 and 6.90 h in group T versus 1.33 h in group S while there were no significant differences between group L and group T as shown in ([Table 2]), also total fentanyl consumption decreased in group L and group T in comparison to group S (149.83 μg in group S vs. 45.00 μg in group L and 44.66 μg in group T) with P value was 0.000 while there were no significant differences between group L and group T ([Table 2]).
|Figure 1 Visual analog score (VAS) at rest at 0.5, 1, 2, 4, 12 and 24 h postoperative at 95% confidence interval (CI). Significant lower pain score in group L and group T in comparison to group S. No significant difference between group L and group T.|
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|Figure 2 Visual analogue score (VAS) during movement at 1/2, 1, 2, 4, 12 and 24 h postoperative at confidence interval 95% (CI). Significant lower pain score in group L and group T in comparison to group S. No significant difference between group L and group T.|
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|Table 2 95% confidence interval of mean difference of the first analgesic request (h) and total postoperative fentanyl consumption (μg)|
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Pulmonary functions including FEV1 and FVC were decreased in all groups at 4 and 12 h postoperatively but CI for mean difference showed that there was a statistically significant less decrease in group L and group T in comparison to group S while there were no significant differences between group L and group T ([Table 3]).
|Table 3 95% confidence interval of mean difference for forced expiratory volume in 1 s, forced vital capacity|
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No statistically significant difference was found between the studied groups according to the occurrence of side effects.
| Discussion|| |
This study evaluated the analgesic efficacy of intraperitoneal administration of lornoxicam combined with levobupivacaine in comparison to tramadol combined with levobupivacaine in patients undergoing elective laparoscopic cholecystectomy surgery under general anesthesia. The findings of this clinical study demonstrated that addition of either lornoxicam or tramadol provided safe, effective and good quality of analgesia when added to levobupivacaine without any significant differences between both groups for intraperitoneal administration without causing adverse effects.
Different mechanisms produced postoperative pain after laparoscopic cholecystectomy including injury to the abdominal wall, intra-abdominal trauma due to gallbladder removal and abdominal distension due to pneumoperitoneum which affected by the volume, type of residual gas, pressure caused by pneumoperitoneum, rate of insufflation and temperature of the gas that used for pneumoperitoneum . So, a multimodal regimen must be used for achieving optimal pain management .
Good quality of postoperative opioid-sparing analgesic regimens may be considered as an advantage to the outpatient laparoscopic cholecystectomy. Intraperitoneal instillation of local anesthetic at the site of operation is commonly used for better relief of postoperative pain and reducing the referred pain at the shoulder region ,.
Several studies considered that postoperative pain and diaphragmatic dysfunction after both laparoscopic and open cholecystectomy were the major predisposing cause of postoperative pulmonary complications ,. Carbon dioxide insufflated during laparoscopic cholecystectomy may cause diaphragmatic irritation with overstretching of the diaphragmatic muscle fibers and phrenic nerve resulting in shoulder pain ,. Tramadol inhibits nociceptive transmission at the spinal level through its monoaminergic activity which inhibits the descending pain pathways .
Lornoxicam besides its analgesic effect it has cyclooxygenase 1 and cyclooxygenase 2 inhibitor effect leading to reduction of the release of pain mediators at the areas of surgical manipulation, lornoxicam is more potent than many other nonopioid analgesics and is well tolerated by patients, it is rapidly eliminated, having a short plasma elimination half-life of 3–5 h so it is suitable for use in the management of acute postoperative pain .
Lornoxicam has been used for improving the quality of postoperative pain in gynecological surgeries , lornoxicam is also as effective as morphine with better tolerated when administered intravenously by patient-controlled analgesia in the treatment of postoperative pain after laminectomy or discectomy .
Sen et al.  reported that lornoxicam and lidocaine combination during intravenous regional anesthesia resulting in a reduction of the onset time of sensory and motor block, reduce pain induced by application of the tourniquet, increased the duration of analgesia and decreased total postoperative analgesic requirements.
This study recorded the prolonged duration of postoperative analgesia, reduction of pain scores and analgesic requirements with significant improvements of the pulmonary functions including FEV1 and FVC postoperatively in the groups that received intraperitoneal instillation of either lornoxicam combined with levobupivacaine or tramadol combined with levobupivacaine than the placebo that received intraperitoneal instillation of saline. In agreement with current study Memedov et al.  found that reduction of postoperative pain in patients who received intraperitoneal instillation of ropivacaine and lornoxicam during laparoscopic cholecystectomy.
In correlation to this study results of the effect of pain management on the pulmonary functions, Spence and Smith  documented that continuous extradural nerve block in patients undergoing vagotomy with gastroenterostomy or pyloroplasty had less effect on the postoperative pulmonary function (FEV1/FVC ratio) and arterial oxygenation than intravenous morphine as the result of better pain control.
Moreover reduction of postoperative pulmonary function may be caused by reflex diaphragmatic inhibition caused by manipulation and local stimulation of the gallbladder and its bed during laparoscopic cholecystectomy .
| Conclusion|| |
Addition of either lornoxicam or tramadol provided safe, effective, less affection of the pulmonary functions and good quality of analgesia when added to levobupivacaine without any significant differences between both groups for intraperitoneal administration.
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Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2]
[Table 1], [Table 2], [Table 3]