Effectiveness of ondansetron as an adjunct to lidocaine intravenous regional anesthesia on tourniquet pain and postoperative pain in patients undergoing elective hand surgery: a systematic review protocol.

REVIEW QUESTION/OBJECTIVE: The objective of this quantitative systematic review is to determine the effects of ondansetron as an adjunct to lidocaine on the tourniquet pain and postoperative pain of American Society of Anesthesiologists (ASA) class 1 or 2 adult patients undergoing elective hand surgery with intravenous regional anesthesia.

BACKGROUND: Both injury and deformity of the upper extremity can result in dysfunction to nerves, tendons and bones which can lead to disability and pain. Hand injuries and deformities encompass an area of upper extremity surgery, wherein isolation and accessibility to peripheral nerves allows for a wide range of anesthesia techniques. Common hand surgeries include carpal tunnel or trigger finger release, Dupuytren's contracture fasciectomy, tendon repair, and ganglion cyst removal. According to the extent of injury or deformity, a general anesthetic, regional anesthetic, monitored anesthetic care (MAC) or local anesthetic may be used for these hand surgeries. Depending on the injury or deformity, local anesthesia may not provide sufficient anesthesia, but a general anesthesia may not be completely warranted either. Typical elective hand surgeries performed under regional anesthesia and MAC may be the ideal anesthetic plan that balances adequate sedation and analgesia. Intravenous regional anesthesia (IVRA), commonly known as a bier block, is a safe and effective anesthetic and is typically utilized in uncomplicated hand or forearm surgeries lasting less than an hour. Intravenous regional anesthesia was first developed by August Bier in 1908 for anesthesia of the hand and forearm. It is a regional anesthetic technique that is easy to perform, with success rates up to 98%. Intravenous regional anesthesia is a simple, reliable and cost-effective anesthesia technique for short ambulatory hand surgery. The IVRA technique is ideal for American Society of Anesthesiologists (ASA) class 1 or 2 patients, which according to ASA classification, are individuals who are healthy with well controlled to no comorbidities.The IVRA technique consists of inserting an intravenous catheter into a peripheral vein of the affected extremity. A double pneumatic tourniquet is applied to the same arm. The extremity is lifted and exsanguinated from distal to proximal with an Esmarch bandage. The proximal cuff of the tourniquet is then inflated to the appropriate pressure; standard 250mmHg for an upper extremity followed by the distal cuff. Insufflation times are limited to a maximum of one and a half to two hours, whereas the total insufflation time should never be less than 20 minutes. The Esmarch bandage is removed, and the local anesthetic is injected via the intravenous catheter to promote anesthesia in the operative area. In addition to the advantages of IVRA, there are disadvantages as well. These disadvantages include, but are not limited to, local anesthetic (LA) toxicity, delayed onset of action, poor muscle relaxation, tourniquet pain, and minimal postoperative analgesia. A method for improving analgesia and IVRA is to add medications to the IVRA solution. The ideal IVRA should include rapid onset of sensory and motor block, reduced LA dose, reduced intraoperative and tourniquet pain, prolonged postoperative analgesia, and minimal side effects.Adjuncts to LA can help offset some of the disadvantages mentioned above. In a systematic review of adjuncts for intravenous regional anesthesia conducted by Choyce and Peng, 29 studies were systematically reviewed to include various adjuncts to LA in IVRA. Adjuncts studied in this review included opioids, tramadol, non-steroidal anti-inflammatory drugs (NSAIDs), clonidine, muscle relaxants, sodium bicarbonate and potassium. The results of this systematic review suggest that NSAIDs have the most potential to offer as adjuncts to IVRA, while opioid adjuncts to IVRA proved to be disappointing as a form of postoperative analgesia. The search for the optimal IVRA adjunct that improves analgesia but has limited side effects is ongoing. More recent studies on adjuncts to IVRA have included medications such as neostigmine, dexmetomidine, nitroglycerin, and ondansetron.Ondansetron is a specific 5-hydroxytryptamine-3 (5-HT3 or serotonin) antagonist, commonly used as an antiemetic drug for prevention or treatment of postoperative nausea and vomiting. Used in the recommended dose range, there are minimal reported side effects, with constipation, dizziness and headache being the most common. 5-HT3 antagonists such as ondansetron possess anti-inflammatory, anesthetic, and analgesic properties which may have a potential role in decreasing pain. 5-HT3 antagonists participate in the pathway of nociception by interfering with peripheral effects of serotonin on nociception. By binding to opioid mu receptors and acting as a potential opioid agonist, the result is a peripheral nociceptive analgesic effect. A study by Deegan shows that there are 5-HT3 receptors on the central spinal terminal, which suggests that ondansetron could have both peripheral and central nociceptive effects. Ambesh et al. found that pain during injection of propofol can be successfully prevented by the administration of 4 mg of ondansetron. In a study performed by Reddy et al., it was shown that 4 mg of ondansetron could significantly reduce pain during the intravenous (IV) injection of rocuronium and propofol.Ondansetron may be useful for its potential anti-in-ammatory effect as an adjunct to medication to reduce acute inflammation. Ondansetron can block sodium channels similar to local anesthetics and produce a local anesthetic effect. It has been shown to be approximately fifteen times more potent than lidocaine. A study by Farouk suggests the addition of ondansetron to lidocaine may improve the quality of IVRA and prolong postoperative analgesia in patients undergoing hand surgery. A study conducted by Honarmand, concluded that the addition of ondansetron to lidocaine for IVRA reduced intraoperative and postoperative analgesic use.Tourniquet pain, which is described as a dull and aching pain sensation, is caused by the nerve compression from the tourniquet. Neuropathic pain produced by nerve compression plays an important role in the etiology of this discomfort. Tourniquet pain is thought to be mediated by impulse propagation via small, unmyelinated, slow-conducting C fibers. The duration of the tourniquet time is directly proportional to the onset of tourniquet pain. In a study by Asik, onset of tourniquet pain ranged from eight to fifteen minutes. Tourniquet pain is a well-known limitation of IVRA and is a factor that can limit the number of times which IVRA can be used for extremity surgery. Lidocaine is one of the most frequently used LAs for IVRA. It has a relatively brief duration of action which may limit the postoperative analgesia. Duration of postoperative analgesia, measured as time to first analgesic requirement ranged from 34 to 45 minutes (median) with LA alone.Outcome measures will include pain assessment for intraoperative tourniquet pain and postoperative pain measured by first analgesic requirement time (the time elapsed after tourniquet release to the first request by the patient for analgesic). Pain will be assessed with a visual analog scale (VAS) (0 = no pain and 10 = worst pain imaginable). A VAS score of more than three would indicate pain threshold has been exceeded.A preliminary search of the Joanna Briggs Database of Systematic Reviews and Implementation Reports, the Cochrane Library, CINAHL, PubMed and PROSPERO has revealed that there are currently no systematic reviews (either published or underway) on the topic of ondansetron as an adjunct to lidocaine intravenous regional anesthesia. Search terms included Zofran, ondansetron, intravenous regional anesthesia, and IVRA. Outcomes of this review will determine if ondansetron, admixed with lidocaine, has an effect on tourniquet pain, and secondly to determine if ondansetron, admixed with lidocaine, has an effect on the duration of postoperative analgesia.