Daily Anesthesiology Research Analysis

INTRODUCTION: Phenylephrine infusion is widely endorsed by guidelines as the preferred prophylactic drug for spinal hypotension in patients undergoing caesarean delivery; however, clinical practice continues to show marked variability in the selection of vasopressor drugs. To address this, we aimed to synthesise current evidence from randomised controlled trials comparing vasopressor infusions for various feto-maternal outcomes in normotensive adult patients undergoing caesarean delivery. METHODS: Randomised controlled trials evaluating maternal and fetal outcomes associated with prophylactic vasopressor infusion were identified through comprehensive database searches. Primary outcomes were the incidence of maternal hypotension and umbilical artery base excess. Secondary outcomes comprised maternal and fetal parameters including: umbilical artery and vein pH; umbilical vein base excess; Apgar scores at 1 min and 5 min; and incidence of maternal intra-operative nausea and vomiting, bradycardia, tachycardia and hypertension. RESULTS: Fifty-five trials involving 5487 patients undergoing caesarean delivery under spinal or combined spinal and epidural anaesthesia using a variety of vasopressor infusions were included in the final analysis. Four drugs-metaraminol, noradrenaline, phenylephrine and adrenaline-were judged to be 'definitely superior' to control (no active vasopressor infusion) for the prevention of hypotension. Umbilical vessel analyses indicated that mephentermine and metaraminol provided superior preservation of both umbilical arterial and venous acid-base balance. DISCUSSION: Current evidence suggests that continuous infusions of α-agonists with mild β-activity (e.g. noradrenaline, metaraminol) are preferable to mixed adrenergic agonists such as ephedrine for preventing maternal hypotension. While these findings reinforce existing recommendations for maternal haemodynamic management, the evidence base for fetal outcomes remains limited. WHAT WE DID: We looked at many research studies where doctors gave medicines to stop low blood pressure during caesarean births. These medicines help keep the mother's blood pressure steady after a spinal anaesthetic. We compared different medicines to see how they affected: mothers' blood pressure and side effects, and babies' health at birth (using blood tests and Apgar scores). In total, we studied results from over 5000 women in 55 research trials. WHY DID WE DO IT: Low blood pressure is common during caesarean births with spinal anaesthetic and can make mothers feel sick and unwell. Doctors use medicines to prevent this, but different hospitals use different drugs. We wanted to find out which medicines work best and are safest for both mothers and babies. WHAT WE FOUND: We found that four medicines worked well to stop low blood pressure: phenylephrine, noradrenaline, metaraminol and adrenaline. Some medicines (especially metaraminol and mephentermine) were better at keeping babies' blood tests healthy. Medicines like noradrenaline and metaraminol worked better overall than older drugs such as ephedrine. These better medicines helped keep mothers' blood pressure steady and reduced sickness and vomiting. This means that using certain modern medicines is likely safer and more effective for mothers during caesarean birth and may also help protect babies—although more research is still needed for babies' outcomes.

BACKGROUND: Remimazolam tosylate, a novel short-acting benzodiazepine, has shown effective and safe sedation in mechanically ventilated patients in intensive care units (ICU) in a phase 2 trial. We conducted a multicenter, randomized, single-blind, actively controlled, phase 3 trial (NCT06222294) for further evaluation. METHODS: Mechanically ventilated patients, requiring sedation for ≥6 h with a target Richmond Agitation-Sedation Scale (RASS) of -2 to 1, were randomized (1:1) to receive intravenous remimazolam tosylate (loading dose, 0.08 mg/kg; maintenance, 0-2.0 mg/kg/h) or propofol (loading dose, 0.3-0.5 mg/kg; maintenance, 0.3-4.0 mg/kg/h). Both allowed for adjusted infusion rates or additional doses to maintain target RASS. Maximum treatment duration was 24 h. Primary endpoint was proportion of patients achieving sedation success, defined as maintaining target sedation range for ≥70% of drug administration time without rescue sedation. Non-inferiority margin was -8%. RESULTS: Between Mar. 12, 2024 and Sep. 24, 2024, 211 patients (mean age, 61.1 years; 63.5% male; 99.1% postoperative) received remimazolam tosylate (n=106) or propofol (n=105). Mean (SD) treatment duration was 11.5±3.6 h for remimazolam tosylate and 11.1±3.1 h for propofol; mean (SD) total dose was 187.1±134.4 mg and 593.7±530.9 mg, respectively. Sedation success rate was 98.1% with remimazolam tosylate and 96.2% with propofol (difference 1.9%, 95% CI -3.3% to 7.8%); mean (SD) percentage of time in RASS target range was 95.1±13.8% vs 95.0±12.9%, and proportion of patients receiving rescue sedation was 0.0% (0/106) vs 1.0% (1/105). Mean (SD) additional doses required was 0.03±0.17 for remimazolam tosylate and 0.18±0.77 for propofol. Adverse event occurred in 81 (76.4%) patients with remimazolam tosylate and 77 (73.3%) with propofol; all were mild-moderate, except one severe with propofol. Mean terminal half-life (SD) of remimazolam tosylate was 1.97±1.62 h. CONCLUSIONS: Remimazolam tosylate demonstrated non-inferior efficacy and good tolerability compared with propofol for short-term sedation in postoperative mechanically ventilated ICU patients.

BACKGROUND AND OBJECTIVES: The popliteal plexus block is a motor-sparing regional anesthetic technique used as an adjunct to multimodal analgesia after total knee arthroplasty. Clinical studies have used varying local anesthetic volumes for the block, reflecting uncertainty regarding the optimal volume. This randomized clinical trial aimed to determine whether using 20 mL of local anesthetic for the popliteal plexus block provides superior analgesic efficacy and early functional outcomes compared with 10 mL after total knee arthroplasty. METHODS: In this single-center, blinded, randomized controlled trial, 120 adults undergoing primary unilateral total knee arthroplasty under spinal anesthesia were randomized to receive a popliteal plexus block with either 10 mL or 20 mL of bupivacaine 5 mg/mL, in addition to a standardized multimodal analgesic regimen including a femoral triangle block. The primary outcome was 24-hour postoperative opioid consumption. Secondary outcomes included the proportion of patients achieving opioid-free analgesia, pain scores, early functional outcomes and patient-reported Quality of Recovery-15. RESULTS: No statistically significant or clinically relevant differences were observed between the two groups in 24-hour postoperative opioid consumption (median 15 (IQR 3.75-30) vs 15 mg (IQR 0-30) oral morphine milligram equivalents; median difference 0 mg, 95% CI -10 to 5; p=0.6), the proportion of patients achieving opioid-free analgesia, pain at rest or during ambulation, ability to ambulate with crutches, motor impairment, or patient-reported quality of recovery. CONCLUSIONS: Use of 20 mL of local anesthetic for the popliteal plexus block as part of a multimodal analgesic regimen after total knee arthroplasty does not provide superior analgesic efficacy or improved functional outcomes compared with 10 mL. Consistent with the principle of using the lowest effective dose and minimizing cumulative local anesthetic exposure, these findings support the use of 10 mL of local anesthetic for popliteal plexus block in clinical practice and in future research. TRIAL REGISTRATION NUMBER: EUCT number: 2024-520204-26-00.