Preemptive Analgesia with Intravenous Tramadol for Postoperative Pain Management in Patients Undergoing Inguinal Hernioplasty: A Randomized Controlled Trial Muhammad Fahim 1, Sadia Ijaz Abbasi 2, Naveed Akhtar Malik 3, Jahangir Sarwar Khan 4, Hamid Hassan 5, Muhammad Mussadiq Khan 5 A u t h o r ` s A f f i l i a t i o n 1 Postgraduate Resident, Dept. of Surgery, Surgical Unit I, Holy Family Hospital Rawalpindi 2 Final Year Medical Student, Rawalpindi Medical College Rawalpindi 3 Assistant Professor of Surgery, Holy Family Hospital Rawalpindi 4 Associate Professor of Surgery, Holy Family Hospital Rawalpindi 5 Professor of Surgery, Rawalpindi Medical College Rawalpindi A u t h o r ` s C o n t r i b u t i o n 1 Conceived the topic of research and designed the study, revised manuscript and supervised the project 2 Data collection, Literature review and manuscript writing 3-4 Helped in study design, data analysis and literature review 5 Supervision and discussion A r t i c l e I n f o Received: Aug 11,2016 Accepted: Nov 25,2016 H o w t o C i t e t h i s M a n u s c r i p t Fahim M, Abbasi SI, Malik NA, Khan JS, Hassan H, Khan MM. Preemptive Analgesia with Intravenous Tramadol for Postoperative Pain Management in Patients Undergoing Inguinal Hernioplasty: A Randomized Controlled Trial. Ann. Pak. Inst. Med. Sci. 2016; 12(3):146-150. Funding Source: Nil Conflict of Interest: Nil Address of Correspondence Muhammad Fahim muhammadfahim92@gmail.com Introduction Generally, inguinal hernias are repaired under spinal anesthesia in the day-surgical department electively ORIGINAL ARTICLE A B S T R A C T Objective: To assess the effectiveness of preemptive analgesia using tramadol in reducing post-operative pain following inguinal hernioplasty. The objective of the study was to compare the post-operativepain with and without administration of pre-emptive intravenous tramadol in patients undergoing inguinal hernioplasty. Study Design: Prospective, randomized, placebo-controlled trial Place and Duration: This study was conducted at Surgical Unit I of Holy Family Hospital Rawalpindi from January 2011 to December 2012. Materials and Methods: Randomization was done by lottery method and patients were divided into two groups. Group I patients received 100mg of tramadol intravenously while group II patients received 4ml of normal saline (placebo) before start of surgical procedure. VAS ratings of pain 6 hours following inguinal hernioplasty was measured in both groups. Results: A total of 248 patients, 124 patients in each group were studied. All patients were male and were in ASA class I and II. Mean age was 37.02 (SD=12.66) in group I, while it was 38.24(SD=13.87) in Group II. VAS scores 6 hours after surgery range from 0 to 10. Mean VAS score 6 hours after surgery was 3.48, (SD=1.67) in patients who received Tramadol (Group I), while it was 6.40, (SD=1.68) in patients who received placebo i.e. normal Saline (Group II) and a p-value of <.0001. Conclusion: This implies that the administration of tramadol before the start of the surgical procedures can produce effective postoperative analgesia. Key words: Pre-emptive analgesia, tramadol, inguinal hernioplasty, postoperative pain. although other types of anesthesia like general, regional or local anesthesia may be used in selective patients. Ann. Pak. Inst. Med. Sci. 2016 146
After recovery from anesthesia, the area of hernioplasty senses mild discomfort in the groin. The post-operative pain thus experienced increases slowly and steadily persisting for longer time. 1 This post-operative pain slows recovery and is known to be one of the important causes of post-operative morbidity. 2 Postoperative pain is experienced maximum in the early post-operative hours and needs meticulous analgesic therapy as inadequate management can lead to several pathophysiological changes in pulmonary and cardiovascular systems. 3 This can delay early ambulation, delay the return of bowel functions and cause delay in acceptance of early discharge by patients. That s why the attenuation of postoperative pain remains an important concern for every surgeon. 4 A variety of post-operative pain management strategies has been sought. They can range from simple oral analgesic agents to epidural catheters and nerve blocks to combat postoperative pain 5. Among them, a simpler strategy of preemptive analgesic agent may be more acceptable for both surgeons and patients as a 2, 3, 6 reliable pain relief technique. The fact that a painful stimulus can sensitize the central somatosensory pathway has led to the suggestion that post-operative pain can be reduced by blocking the original painful stimulus to sensitization of pain pathway. This interrupts the transmission of noxious perioperative inputs to the spinal cord and alleviates pain intensity, reduces analgesic consumption and delay time to first analgesic requirement after surgery. 2,7 Preemptive analgesia is an effective approach to achieve pain-free state in postoperative period by administration of pharmacological agents. This technique alters the processing of painful stimuli resulting from tissue trauma in the central nervous system thereby reducing postoperative pain. 8-12 There are various pharmacological agents that have been used with variable analgesic activity. Among them are the NSAIDs, opioids and local anesthetic agents. Tramadol is a synthetic, centrally acting opioid analgesic with a potent opioid metabolite. It is considered to produce less respiratory depression and has no significant cardiac effects as compared to other opioids. 1,13 It can help in accelerated recovery by providing prolonged postoperative pain relief. 13,14 In keeping with an evidence based approach to patient care it is important to understand the effect of timing of administration of the drug in controlling post-operative pain. The purpose of this study was to evaluate the effectiveness of preemptive analgesia using tramadol in reducing post-operative pain following inguinal hernioplasty. Materials and Methods It was a randomized, double-blinded, placebo-controlled study conducted in Surgical Unit-I of Holy Family Hospital, Rawalpindi from January, 2011 to December, 2012.Non probability consecutive sampling was done. All patients scheduled for hernioplasty for inguinal hernia between age 20-70 years and American Society of Anesthesiologists (ASA) I or II physical status were included in this study. Patients with known allergy to tramadol and analgesics abuse were excluded from study. Similarly, the patients in whom operative complication necessitated any procedure more than hernioplasty or any physical or psychological problem that may influence pain response or ability to comply study were also excluded. This trial was approved by the Research Ethics Committee of Holy Family Hospital and written informed consent was obtained in all cases. The patients scheduled for inguinal hernioplasty meeting inclusion criteria were enrolled in the study. They were explained to understand visual analogue scale for pain assessment where one end of the scale represent no impact of pain at all and the other end is representative of extreme or severe impact of it that the patient had ever experienced. The VAS ratings of pain was measured 6 hours post operatively with the 10-cm gauge as the primary outcome, i.e. subjective pain intensity score was established based on a 0 10 cm linear VAS (0 = no pain; 10 = worst pain imaginable). All patients were kept blinded to the group allocated throughout the study. Each individual was randomly assigned to one of two groups by lottery method. The envelope was opened in the operating room by the anesthetist 15minutes before induction of anesthesia to indicate which patient is to receive intravenous tramadol, 4ml equivalent to 100mg (Group I) or 4ml of 0.9% NaCl (Group II, placebo). Severity of pain was assessed in post anesthesia care unit (PACU) by trainee doctor at 6hours after surgery by using VAS. Standard post-operative regimen for all patients was a tablet containing a mixture of paracetamol with dextroproxyphene given on as required basis. All the data was recorded in the specially designed Performa. Data was analyzed on SPSS version 12. Categorical variables such as gender and ASA class were expressed as frequencies. Pain scores and age were expressed as mean and standard deviation. Independent sample t- test Ann. Pak. Inst. Med. Sci. 2016 147
was used to compare pain scores between two groups. P value <0.05 was considered significant. Results From January 2011 to December 2012, 248 consecutive outpatients matching the inclusion and exclusion criteria were enrolled on a convenient sampling bases; 124 patients received preemptive analgesia with intravenous tramadol 100mg (Group I), and 124 patients received 4ml of Normal saline intravenously (Group II). None of the patients was lost to follow up or needed any surgical procedure other than Hernioplasty as planned. Our study population was in age group of 20 to 70 years. Mean age of patients in our study was 37.65 years. Mean age was 37.02 (SD=12.66) in group I, while it was 38.24(SD=13.87) in Group II. In this study, all 248 patients were male and none of the patients was female, in either of the group. There were 184(74.2%) patients who were in ASA Class I, while there were 64(25.8%) patients who were included in ASA Class II.VAS score 6 hours after surgery range from 0 to 6 with mean of 3.48 (SD=1.67) in patients who received Tramadol (Group I), while it range from 4 to 10 and a mean of 6.40 (SD=1.68) in patients who received placebo i.e. normal Saline (Group II). P-value = 0.000. These results are shown in Table. Table 1: Characteristics of study population Group I (Tramadol) Group II (Plcebo) No. of Patients 124 124 Lost to follow up 0 0 Mean age (years) 37.02 3824 VAS Mean 3.48 6.40 Standard deviation 1.670 1.682 P value 0.000 Discussion Currently a wide variety of literature exists on the treatment of postoperative pain. A debate is going on within the literature on the best analgesic agent, timing and route of administration etc. despite the availability of various treatment regimens. Without adequate guidelines the patient is placed at risk of too much or too little and inappropriate analgesic therapy to control pain. Current clinical practice is designed to minimize pain in the perioperative period based on the scientific evidence from peer-reviewed medical literature. Woolf in 1983 paved the concept of preemptive analgesia to reduce the magnitude and duration of postoperative pain. He showed the evidence for a central component of post-injury pain hypersensitivity in experimental studies. 15 Later on, the experimental data demonstrated that various anti-nociceptive techniques were more effective in reducing the post-injury central sensitization phenomena when applied before injury as compared with their administration after injury. 16 Eventually, these findings were taken into clinical testing of the hypothesis. 17 The topic of preemptive analgesia remains controversial; there have been reports in favor as well those against the use of preemptive analgesia. 13 In general, it is considered that preemptive analgesia is more effective than the preventive one. The main reasons for such recognition is based on the theories that preoperative medications could block the nociceptive input and increase the threshold for nociception, thereby leading to decreased noci-ceptor receptor activation before the tissue injury. 18 On the other hand, the intraoperative medication could not totally interrupt the ongoing nociceptive input and merely produce limited analgesic effect. 19 Because of this effect, it is sometimes used as an adjunct to anesthesia to control postoperative pain. 19 Although such contrasting viewpoints appeared, our data strongly advised that preemptive administration of analgesics was an effective way of treating pain originating from groin incision in patients with inguinal hernioplasty. There are conflicting results concerning preemptive and preventive administration of different groups of analgesics. Certain groups of analgesics have shown the positive results in various clinical trials in humans. These analgesic agents include NSAIDs (non-steroidal antiinflammatory drugs) like diclofenac, lornoxicam, ketorolac, tramadol, local anesthetic agents and nerve blocks etc. 20-22 The analgesics effects of these agents in controlling postoperative pain and analgesic demand is variable. These effects depend upon various factors and include the dose, route and timings of their administration in relation to surgery. Ketamine has been used previously in laparoscopic cholecystectomy patients to achieve an effective pain-free state post-operatively. It also increased the analgesic effects of tramadol when used preemptively. 23 Similarly, meloxicam has also produced better results when used as premedication in cases of abdominal hysterectomy. 24 A meta-analysis by Ong et al assessed the ability of preemptive analgesic interventions to attenuate postoperative pain, decrease postoperative analgesic requirements, and delay the time to first rescue Ann. Pak. Inst. Med. Sci. 2016 148
analgesia. 25 This meta-analysis demonstrated an overall beneficial effect in selected analgesic regimens that was most pronounced after epidural analgesia, local wound infiltrations, and systemic NSAID administration. 25 In addition, investigations of the effect of preemptive tramadol on postoperative pain were evaluated and showed interesting and meaningful results, no matter which delivery manner was used, either intramuscular, intra-articular or intravenous, the premedication of tramadol produced effective pain relief. 26-29 The data of this study demonstrated that intravenous preemptive analgesia with tramadol (100 mg) prior to inguinal hernioplasty produced superior analgesic effects when compared with the placebo group. The analgesic effect of preoperatively administered tramadol emanates before the hurtful stimulus of incision and continues adequately in the post-operative period as well. In few other studies, the analgesic effects of tramadol has been studied when given as premedication along with patient controlled analgesia continued postoperatively. 30 In comparison, this trial has focused on analgesic effects of tramadol administered as single bolus preoperatively. The present data is expectedly interesting because it shows that it is an effective procedure in producing pain relief effect postoperatively. LIMITATIONS: Time to first rescue analgesia and total amount of analgesic agents were not studied in this controlled trial. Further studies are needed to fill this gap in knowledge. Conclusion Pre-emptive delivery of tramadol expressed effective analgesia 6 hours after inguinal hernioplasty. VAS score was high in group who did not received preemptive tramadol. This implies that the administration of tramadol before the start of the surgical procedures can produce effective postoperative analgesia in the context of inguinal hernioplasty. References 1. 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