Preemptive analgesic efficacy of intravenous diclofenac versus IV paracetamol in orthopedic surgeries: A prospective randomized, double blind, controlled study.

The relief of post-operative pain represents one of the clinical areas on which precise standardization does not exist despite the enormous data published in the literature, that is, it is still inadequately relieved despite substantial improvements in the knowledge of mechanisms and treatment of pain. Different treatments have been proposed to relieve pain after orthopedic surgery. Administration of analgesics prior to the start of surgery is used by many as a method of reducing postoperative pain. Preemptive analgesia is an antinociceptive treatment that prevents the establishment of lateral processing of afferent input which amplifies postoperative pain.[1] So it is important to start analgesia before incision and cover both periods of surgery and initial postoperative period. Studies have shown that it not just relieve the pain but also decreases length of intensive care or hospital stay and morbidity*.[2,3] Multimodal analgesic regimen including opioids, acetaminophen or non-steroidal anti-inflammatory drugs (NSAIDs)and the local anesthetics can be administered either alone or in combination has been administered to achieve adequate analgesia without untoward side effects.*[4] The  American society of anesthesiologists (ASA) acute pain management practice guidelines  state  that   clinicians  should  use  multimodal  analgesia  whenever possible  in  the  perioperative  setting. The ASA recommends that all surgical patients receive an around-the-clock regimen of acetaminophen and a NSAID unless contraindicated,  and  that   the  dosages  and  duration of therapy should be  individualized,  balancing  efficacy  with  the  risk of   adverse  events.[5] For this reason, it was decided to compare efficacy of preemptively used intravenous (IV) diclofenac with IV paracetamol for the postoperative pain relief in patients undergoing orthopedic surgery.

The study would be conducted in 100 ASA physical status grade I and II, of either sex, between the age group of 18-65 years scheduled for elective upper limb orthopedic surgeries under general anesthesia (GA) in the year 2012-2013. Patients would be admitted at least 24 hours before surgery. Detailed history, examination and relevant investigations like complete blood count, renal/liver function tests, coagulation profile, X-ray chest and ECG will be carried out. Patients posted for unilateral or bilateral upper limb surgery e.g., shoulder, humerus and elbow surgery were included while those allergic reaction to study drugs, gastric ulcer complaints for last 6 months, coagulopathy, alcohol or drug addicts, neurological or psychiatric illness and clinically significant major organ disease were excluded from the study. Before enrolling to the study, all patients were informed about the aims, methods, anticipated benefits and potential hazards of the study. An informed written consent from the patients and approval from the local ethics committee would be obtained. Patients were prepared by 8 hours of preoperative fasting. Tab alprazolam 0.25mg and pantoprazole 40mg per orally were given at bed time as premedication. Intravenous infusion line will be  started with ringer lactate 60 minutes before the commencement of anaesthesia. In the preoperative holding area patients were randomly assigned to one study group using random no. table (n=50 in each). The involved anesthesiologist kept unaware of group allocated and medication administered to them as per study protocol. Group P patients were given intravenous 1g paracetamol in 100ml preparation wrapped by opaque sheet, 30 min before surgery where as group D patients were given intravenous 75 mg diclofenac (inj. Dynapar AQTM) diluted in 100 ml 0.9% NS also wrapped by opaque sheet, 30 min before surgery. In Operation Theater, routine monitors (ECG, NIBP and Pulse oximeter) were attached. After preoxygenation with 100% oxygen for 3-5 minutes, all patients were induced with fentanyl 2mcg/kg, sodium thiopentone 5 mg/kg and succinylcholine 2mg/kg intravenously to facilitate endotracheal intubation. Neuromuscular relaxation will be achieved with non-depolarizing muscle relaxant atracurium besylate 0.5mg/kg and top up dose will be 1/4th of the loading dose. Anaesthesia will be maintained with oxygen and nitrous oxide mixture (40:60) and isoflurane (0.5-1%) delivered by IPPV using circle absorber system. Residual neuromuscular block will be reversed with neostigmine 0.05mg/kg and glycopyrrolate 0.01 mg/kg at the end of surgery. Pulse rate, blood pressure, and oxygen saturation were recorded 5 minutes before induction and every 10 minutes intraoperatively and after extubation.

Intraoperative pain would be assessed by hemodynamic parameters (inadvertent rise in HR, BP) while postoperative pain assessment using visual analog score (VAS) ranging from 0-100 mm will be done at 15 min, 30min, 1 hr, 2hrs, 4hrs and 6hrs and rescue analgesia will be given in the form of fentanyl 1mcg/kg or usually 50 mcg IV, if VAS score >3. Also, any postoperative complication will be noted and treated accordingly.

The sample size was calculated on the assumption of a standard deviation (SD) of 0.6 of the expected difference from a previous study[6] with a power of >80% to detect this difference, using the student t-test with type I error (α) of <5%. The calculated sample size came out as 44 in each group. A total of 50 patients in each of the two groups including 10% drop outs were included to complete the study. Comparative evaluation between groups D and P will be done using 2x2 contingency table with student t-test, Chi-square test or Fisher’s exact test by GraphPad Prism version 7.00 for Windows, GraphPad Software, La Jolla California USA, www.graphpad.com.