Efficacy and safety of intrathecal morphine for analgesia after lower joint arthroplasty: a systematic review and meta‐analysis with meta‐regression and trial sequential analysis

Abstract

Widespread adoption of intrathecal morphine into clinical practice is hampered by concerns about its potential side-effects. We undertook a systematic review, meta-analysis and trial sequential analysis with the primary objective of determining the efficacy and safety of intrathecal morphine. Our secondary objective was to determine the dose associated with greatest efficacy and safety. We also assessed the impact of intrathecal morphine on respiratory depression. We systematically searched the literature for trials comparing intrathecal morphine with a control group in patients undergoing hip or knee arthroplasty under spinal anaesthesia. Our primary efficacy outcome was rest pain score (0-10) at 8-12 hours; our primary safety outcome was the rate of postoperative nausea and vomiting within 24 hours. Twenty-nine trials including 1814 patients were identified.Rest pain score at 8-12 hours was significantly reduced in the intrathecal morphine group, with a mean difference (95%CI) of À1.7 (À2.0 to À1.3), p < 0.0001 (19 trials; 1420 patients; high-quality evidence), without sub-group differences between doses (p = 0.35). Intrathecal morphine increased postoperative nausea and vomiting, with a risk ratio (95%CI) of 1.4 (1.3-1.6), p < 0.0001 (24 trials; 1603 patients; high-quality evidence). However, a sub-group analysis by dose revealed that rates of postoperative nausea and vomiting within 24 hours were similar between groups at a dose of 100 µg, while the risk significantly increased with larger doses (p value for sub-group difference = 0.02). Patients receiving intrathecal morphine were no more likely to have respiratory depression, the risk ratio (95%CI) being 0.9 (0.5-1.7), p = 0.78 (16 trials; 1173 patients; highquality evidence). In conclusion, there is good evidence that intrathecal morphine provides effective analgesia after lower limb arthroplasty, without an increased risk of respiratory depression, but at the expense of an increased rate of postoperative nausea and vomiting. A dose of 100 µg is a 'ceiling' dose for analgesia and a threshold dose for increased rate of postoperative nausea and vomiting.

Impact of low-dose intrathecal morphine on orthopedic surgery: a protocol of a systematic review and meta-analysis of randomized controlled trials

“…If the corresponding author failed to reply, we will take the median (IQR) as approximations of the mean (SD), by estimating the mean as equivalent to the median, and the SD as the IQR divided by 1.35, or the range divided by 4 as Gonver et, al. did [6].…”

“…Intrathecal morphine (ITM) has been proven to be an ideal solution, firstly induced to clinical application in 1979, as the drug is administered directly into the cerebrospinal fluid, where the opioid acts close to the central nervous system, is effectively performed at dosage of typically no more than 1 mg of morphine [3, 4]. However, previous evidence has shown that both efficacy and side-effects are dose-dependent in various surgical scenarios[4-6]. Therefore, weighing the benefits and potential side effects should be a primary concern when determining the dosage of ITM in clinical use.…”

“…Therefore, weighing the benefits and potential side effects should be a primary concern when determining the dosage of ITM in clinical use. Compared with a higher dosage, administration of low-dose morphine (<100 μg) intrathecally has been validated as the optimal dosage by previous studies, for its effectiveness with minimal side-effects [6, 7]. In recent decades, multiple randomized controlled trials have emerged, proving the efficacy and safety of systematic use of low-dose ITM on patients undergoing orthopedic surgeries, and therefore an updated synthesis of the literature is needed.…”

The Relationship Between Postoperative Opioid Analgesia and Sleep Apnea Severity in Patients Undergoing Hip Arthroplasty: A Randomized, Controlled, Triple-Blinded Trial

“… 4 Likewise, we have also studied the impact of low dose of intrathecal morphine, 5 which is commonly administered in anesthesia to provide effective postoperative analgesia. 6 The administration of short-acting anesthetic agents or low dose intrathecal morphine did not worsen sleep apnea severity. 4 , 5 …”

Regional anesthesia and enhanced recovery: we need more data

“…The relevance of these data is uncertain. The evidence published to support a lower dose of opioids in lower limb surgery remains applicable in terms of adverse effects, as these are independent of surgery but rather dependent on the intrathecal morphine dose itself 6. Given that there remains a dearth of evidence to support any dose ranges in colorectal surgery and the side-effect profile is not procedure specific, we respectfully disagree with the suggestion of high doses until robust safety and efficacy data support it.…”