PCA Ketamine-Morphine Versus PCA Morphine as Post-Operative Analgesia in Colorectal Surgery.

INTRODUCTION

Patient-controlled analgesia (PCA) has been an established efficient and safe technique for providing postoperative analgesia [1-3]. It is a delivery system with which patients self-administer predetermined doses of analgesic medication to relieve their pain [1]. A reviewed meta-analysis conducted by McNicol et al (2015) provided evidence that PCA opioids provide superior analgesia in comparison to conventional intravenous opioids analgesia [2]. PCA has been associated with better pain relief and patient satisfaction with less postoperative complications and side effects [1-3].

Despite years of advances in pain management, opioids have been the mainstay for the treatment of postoperative pain particularly in moderate to severe pain [1-3]. A variety of opioids have been used for PCA, namely morphine, fentanyl, pethidine and oxycodone. Of all the opioids, morphine is the most studied drug and remained the drug of choice for PCA including in Malaysian hospitals' settings [1,4]. However, it is also associated with known side effects such as respiratory depression, sedation, nausea and vomiting, pruritus, constipation and urinary retention [2,4]. The concept of multimodal analgesia hence was introduced to reduce opioid-related side effects. Adjuvants such as acetaminophen and non-steroidal anti-inflammatory drugs are commonly used nowadays in combination with opioids as opioid-sparing agents [5, 6].

Ketamine, an N-methyl-D-aspartate (NMDA) antagonist, has undergone a recent resurgence of interest among acute care providers as an adjunct in acute pain management [5-7]. Ketamine at sub-anaesthetic dose (0.2-0.5 mg/kg) produces intense analgesia [5-9]. The analgesic effects of ketamine are primarily due to its activity in the thalamic and limbic systems which are responsible for interpretation of painful signals and modulation of pain [9]. Activation of NMDA receptors located at the dorsal horns, by excitatory neurotransmitters particularly glutamate, induced by peripheral nociceptive stimuli results in hyperexcitability of the dorsal root neurones, which is the pathophysiology of acute pain. It has also been reported that μ receptor activation by opioids leads to a sustained increase in glutamate synaptic effectiveness at the level of NMDA receptors [8]. The combination of ketamine, a non-competitive antagonist at the NMDA receptor with morphine hence will have a synergistic effect and this may allow a reduction in doses of both drugs and potentially reduce the side effects related to both [8-18].

Since its development in 1962, various studies have been conducted to prove the efficacy of ketamine as postoperative analgesia and as an opioid-sparing agent [7]. A review by Laskowski et al. (2010) described IV ketamine improved the quality of pain control, in addition to decreased opioid consumption with particular benefits observed in painful procedures, including upper abdominal, thoracic, and major orthopaedic surgeries [7]. Carstensen et al. (2010) in a qualitative review comparing PCA ketamine-morphine with PCA morphine alone also described the superior efficacy of ketamine-morphine in providing pain control with a significantly higher incidence of opioid-related side effects including sedation, nausea, vomiting, pruritus, urinary retention and desaturation in the morphine group [10]. In comparison to opioids, ketamine's lack of respiratory depressant effects also favours its use as an opioid adjunct in patients with airway and respiratory compromise, such as morbid obesity and post-thoracotomy patients [7,10-13].