Most Effective Opioid Analgesia in Ambulatory Surgeries: a Randomized Control, Investigator Blinded, Parallel Group With Superiority Design Study of Morphine Versus Hydromorphone

There has been an exponential increase in the number of day case surgical procedures also called as ambulatory surgeries (AS), over the last 2 years.(1) Currently around 70% of procedures are being done as AS, with known benefits to patients and hospitals.(2) Its efficiency and cost effectiveness depends upon its organization and delivery of services. Pain and PONV are recognized as the leading factors affecting the quality of services delivered under AS,(1,3) and they affect the recovery, discharge, and overall satisfaction of patients.(4,5) According to literature, postsurgical pain could be inadequately treated in 30%-60% of patients and 30%-40% of AS patients suffer from significant PONV.(3,6,7) It is estimated that a single episode of PONV can prolong the PACU stay by 25 mins,(8) and patients rate PONV to be the most undesirable outcome associated with anesthesia.(4) Despite the increasing use of non-opioid analgesics, opioid analgesics have remained the primary modality in moderate to severe pain.(7) They cause several side effects such as drowsiness, sedation, PONV, itching and respiratory depression. Appropriate selection of opioid medications becomes significantly important to deliver safe and effective analgesia with minimal side effects. Although M has been the most commonly used medication, HM is also being increasingly used.(9) We do not yet know whether HM is more effective than M in AS patients. Both M and HM exert no ceiling effect for their analgesia, and by this nature incomplete or inadequate analgesia is related to the appearance of side effects.(10) Hence clinical effectiveness of opioids, relative to each other, is reflected not just by satisfactory analgesia, but by a combination of 'satisfactory analgesia with limited side effects'. Clinical observation suggests that HM is clinically better by providing superior or equivalent analgesia with decreased side effects.(9) HM is a semi-synthetic morphine derivative that differs from M in its position 6 of the benzol ring, where it has a keto-group instead of a hydroxy group, making it 5-10 times more potent and enhances its distribution to cerebral tissues, making for easier titration.(9) The t1/2 Ke0 (transfer life from plasma to effect site) is 1.6hr - 4 hr for M, compared to 18-38 min for HM.(9,10) It is observed that health care providers may be willing to provide higher dose of HM compared to M in EMU, as its actual quantity of drug is much smaller and therefore appears to cause less concern.(12, 13) Our literature review showed that there are no previous studies comparing these 2 medications in AS patients. The lone systematic review compared various acute and chronic pain studies, in various routes of drug administration.(9) Of the 11 studies identified; only 4 were done in acute pain settings.(13-16) Two of them were done by the same author in ER settings. Chang et al noted that HM reduced the mean pain scores by 1.3 units [95% CI= (-2.2 to -0.5)] compared to M in 198 adults treated in ER.(12,13). However it did not show much difference in geriatric population.14 In perioperative settings, Hong et al studied the difference in nausea between the 2 medications in 50 patients using PCA and found no difference.(15) Rapp et al studied various effects between the 2 medications in 61 surgical patients using PCA. There is not much clarity about their primary outcome; however they found the effects to be similar.(16) Both these studies had smaller sample sizes. The meta-analysis performed demonstrated that the HM does provide better analgesia than M, with a small effect size; Cohen's d=0.266 (p=0.012).(9) Looked at acute pain alone it was statistically significant (p=0.006), compared to chronic pain (p=0.889). It was noted that that there is a definite lack of comparative studies between them in surgical settings.