Measurement of drug concentration and bacterial contamination after diluting morphine for intrathecal administration: an experimental study.

BACKGROUND: Low concentrations of morphine are required for safe dosing for intrathecal injections. Sometimes, manual dilution of morphine is performed to achieve these low concentrations, but risks dilution errors and bacterial contamination. The primary goal was to compare the concentrations of morphine and bupivacaine between four groups of syringes. The secondary goal was to investigate the difference in contamination rate between these groups. METHODS: Twenty-five experienced anesthesia providers were asked to prepare a mixture of bupivacaine 2.0 mg/ml and morphine 60 µg/ml using 3 different methods as clean and precise as possible. The fourth method used was the aspiration of ampoules prepared by the pharmacy. The concentrations of morphine and bupivacaine were measured by High-Pressure Liquid Chromatography (HPLC). The medication was cultured for bacterial contamination. RESULTS: Group 1 (median 60 µg/ml; 95% CI: 59-110 µg/ml) yielded 3 outliers above 180 µg/ml morphine concentration. Group 2 (76 µg/ml; 95% CI: 72-80 µg/ml) and 3 (69 µg/ml; 95% CI: 66-71 µg/ml) were consistently higher than the target concentration of 60 µg. The group "pharmacy" was precise and accurate (59 µg/ml; 95% CI: 59-59 µg/ml). Group 2 and "pharmacy" had one contaminated sample with a spore-forming aerobic gram-positive rod. CONCLUSION: Manually diluted morphine is at risk for deviating concentrations, which could lead to increased side-effects. Medication produced by the hospital pharmacy was highly accurate. Furthermore, even when precautions are undertaken, contamination of the medication is a serious risk and appeared to be unrelated to the dilution process.

A double-blind, randomised, placebo-controlled trial comparing intrathecal bupivacaine with bupivacaine plus morphine to reduce delirium in patients with hip fractures-Salmon-Mind trial study protocol.

Background: Surgical treatment of proximal femur fractures is complicated by postoperative delirium in about one-third of patients. Pain and opioid consumption are modifiable factors that may influence the incidence of delirium.1 An intrathecal injection of morphine may lead to a reduction in postoperative pain and reduced systemic opioid consumption. In current practice, the addition of morphine to intrathecal anaesthesia is commonly used but depends on the anaesthesiologist's preference. Recently, a retrospective study found that intrathecal morphine was independently associated with a lower incidence of delirium. However, this has to be confirmed in a prospective, randomised study. We hypothesise that using intrathecal morphine reduces postoperative pain and opioid consumption during the first 48 h after surgery and reduces the incidence of delirium during hospital admission. We also seek additional evidence of the association between neuronal injury (delirium) and neurofilament light in serum of patients with proximal femur fractures. Objective: The primary objective is to compare the incidence of delirium. The secondary objectives are to compare pain scores, systemic opioid consumption, and (opioid-related) side-effects. The tertiary objective is to test the association between intrathecal morphine and neurofilament light as a marker of neuronal injury. Study design: A double-blind, randomised, placebo-controlled intervention study is proposed. Study population: All patients with a proximal femur fracture who are scheduled for surgery under spinal anaesthesia. Intervention: The intervention is the addition of morphine 100 µg to the intrathecal injection for spinal anaesthesia. The intervention group will receive a mixture of bupivacaine 10 mg and morphine 100 µg. The control group will receive bupivacaine 10 mg. Clinical trial registration: EU Clinical Trials Register: EudraCT number 2020-002143-27.