BACKGROUND
•Intrathecal (IT) opioids are an efficacious and widely used modality to treat postoperative pain after colorectal surgery
•(IT) opioids confer superior postoperative analgesia to systemic opioids as they deliver analgesia directly to their site of action while curtailing the undesired side effects of the parenteral route.
•While morphine has been established as the “gold” standard, hydromorphone has gained popularity as an alternative
•A prospective trial in women undergoing Cesarean delivery showed optimal dose doses to be 150 mcg for IT morphine and 75 mcg for IT hydromorphone
In colorectal surgery, clinical dosing of neither IT morphine nor hydromorphone is based on anecdotal evidence and retrospective studies and the optimal dose for neither agent has been established in a randomized prospective trial.
OBJECTIVES
ØDetermine the optimal dose expressed as ED90 for IT morphine and hydromorphone in patients undergoing minimally invasive colorectal surgery
ØAssess overall quality of recovery and presence of opioid side effects across the entire` dose range for both agents
METHODS
•Double-blinded prospective trial (NCT04752033)
•Patients who met the inclusion criteriarandomized into either morphine or hydromorphone arm
•ED90 was defined a dose needed to achieve pain numerical rating scale (NRS) score ≤4 with postoperative opioid requirements ≤15 opioid morphine equivalent (OME) 12 hours after medication administration in 90% patients
•ED90 for both drugs determined by a sequential up-and-down method using a biased coin design
•Dose range examined:
Morphine: 25 - 50 - 100 (starting dose) - 150 - 200 - 250 - 300 - 350 - 400 mcg
Hydromorphone: 10 - 25 - 50 (starting dose) - 75 - 100 - 125 - 150 - 175 - 200 mcg
•Secondary outcomes included NRS pain scores, Overall Benefits of Analgesia (OBAS), Quality of Recovery (QoR) 15, opioid consumption and side effects, presence of adverse events, and patient satisfaction for up to 48 hours
•All patients received a standardized regimen of multimodal analgesics and antiemetics`
RESULTS
•ED50 was calculated instead and was 100 mcg (95% CI was below the lowest dose) for morphine and 75 mcg (95% CI 50–200 mcg) for hydromorphone.
•While the failures resulted in an increase in the dose of both medications, most patients (65% for morphine and 55% for hydromorphone) met the criteria for success in terms of both NRS scores and OME requirements across the entire dose range (Figure 2).
•As the dose of hydromorphone increased, moderate to severe pruritus increased (P=0.009; Table 2)
DISCUSSION
First double-blinded, prospective, dose-finding trial of IT opioids in patients undergoing colorectal surgery
Inability to determine ED90 attributed to:
ED90 outside of the dose range
Procedure or population heterogeneity
Small magnitude of effect in the setting of multimodal analgesia
Inconsistent pattern of administration of PRN opioids
Pruritus noted for both agents, with a statistically significant difference noted with dose escalation of hydromorphone
CONCLUSIONS
ED50 determined for both IT morphine and hydromorphone, and was 100 mcg and 75 mcg, respectively)
High satisfaction for both agents across the entire dosing regimen with no observed serious adverse events
