Opioid-free versus opioid-sparing anaesthesia in ambulatory total hip arthroplasty: a randomised controlled trial.

BACKGROUND: Enhanced recovery after surgery pathways are essential for ambulatory surgery. They usually recommend lower intraoperative opioid use to avoid opioid-related adverse effects. This has led to opioid-sparing anaesthesia (OSA) techniques, with the extreme approach of opioid-free anaesthesia (OFA) mostly with dexmedetomidine. As evidence is lacking in day-case primary total hip arthroplasty, this study was performed to assess the potential benefits in postoperative analgesia of OFA over OSA. METHODS: In this single-centre, prospective, triple blind study, we randomly allocated 80 patients undergoing day-case primary THA under general anaesthesia. Patients received a total intravenous anaesthesia with a laryngeal mask and multimodal analgesic regimen with non-opioid analgesics. The OSA group received low dose of sufentanil, and the OFA group received dexmedetomidine The primary outcome was the opioid consumption in the first 24 h in oral morphine equivalents (OME). RESULTS: There was no difference in median cumulative OME consumption at 24 h between the OSA and OFA groups (12 [0-25] mg vs 16 [0-30] mg, respectively; P=0.7). Pain scores were similar and low in both groups with comparable walking recovery time. Adverse events were sparse and equivalent in both groups except for dizziness, which was more frequent in the OSA group (P<0.05). CONCLUSIONS: In day-case total hip arthoplasty under general anaesthesia, opioid-free anaesthesia and opioid-sparing anaesthesia both provide early recovery and effective postoperative pain relief. When compared with opioid-sparing anaesthesia, opioid-free anaesthesia does not decrease opioid consumption in the first 24 h. These findings do not suggest any significant benefit from complete intraoperative avoidance of opioids. CLINICAL TRIAL REGISTRATION: NCT0507270.

Combined proximal or distal nerve blocks for postoperative analgesia after total knee arthroplasty: a randomised controlled trial.

BACKGROUND: Many regional anaesthetic techniques have been proposed to manage pain after total knee arthroplasty, but the best approach is unclear. We compared opioid consumption in the first 48 h between two different regional anaesthesia strategies in patients undergoing total knee arthroplasty. METHODS: In this single-centre, prospective study, we randomly allocated 90 patients to a combination of IPACK (interspace between popliteal artery and capsule of the posterior knee), triangle femoral and obturator nerve blocks (distal group), or a combination of sciatic, femoral, obturator, and lateral femoral cutaneous nerve blocks (proximal group). All patients received an opioid-sparing general anaesthesia regimen. The primary outcome was opioid consumption in the first 48 h. Secondary outcomes included opioid consumption in the first 24 h and verbal rating pain scores in the first 48 h. RESULTS: There was no difference in median cumulative oral morphine equivalent consumption at 48 h between the distal and the proximal block groups (33 [18-78] mg vs 30 [22-51] mg, respectively; P=0.29). Median oral morphine equivalent consumption at 24 h was higher in the distal group compared with the proximal group (30 [13-59] vs 15 [0-18], respectively; P<0.001). Verbal rating pain scores were lower in the proximal group compared with the distal group on arrival to the postanaesthesia care unit and at 6 and 12 h. CONCLUSIONS: In patients undergoing total knee arthroplasty under total intravenous general anaesthesia with a multimodal analgesia regimen, proximal nerve blocks resulted in improved pain scores in the first 12 h and reduced opioid consumption in the first 24 h when compared with distal nerve blocks. No difference in pain scores or opioid consumption was seen at 48 h. CLINICAL TRIAL REGISTRATION: NCT04499716.

Total knee arthroplasty under quadruple nerve block with ropivacaine 0.32%: effect of addition of intravenous dexmedetomidine to intravenous dexamethasone on analgesic duration.

BACKGROUND AND OBJECTIVES: Peripheral nerve blocks reduce postoperative pain and enhance recovery after total knee arthroplasty (TKA). This study aims to assess the benefits of addition of intravenous dexmedetomidine (DexM) to intravenous dexamethasone on the analgesic duration of quadruple nerve blocks. METHODS: This double-blind, randomized, controlled trial prospectively enrolled 90 patients scheduled for TKA under quadruple nerve blocks (sciatic, femoral, obturator, and lateral femoral cutaneous nerves blocks) with 70 mL, 0.32% ropivacaine. All patients received systemic dexamethasone 10 mg. Patients were randomized to receive DexM (2 µg/kg, intravenous) or placebo (1:1 ratio). The primary endpoint was the duration of analgesia defined as the time to first request for rescue analgesia (oxycodone). RESULTS: Kaplan-Meier curves for the first analgesic request were similar between groups (log-rank test; p=0.27). Median (IQR) duration of analgesia was similar between placebo (1575 min (1211-1952)) and DexM (1470 min (1263-1700)) groups (p=0.56). Cumulative consumption of oxycodone at the 48th hour was 20 mg (10-30) and 30 mg (20-40) in placebo and DexM groups, respectively (p=0.14). The day after surgery, 93% and 89% of patients were able to walk in placebo and DexM groups, respectively (p=0.46). Intravenous DexM was associated with bradycardia, hypotension and longer recovery room stay (p<0.05 for all comparisons). CONCLUSIONS: In a multimodal analgesic regimen, addition of systemic DexM (2 µg/kg) to systemic dexamethasone does not prolong the analgesic duration of quadruple nerve block with ropivacaine 0.32% after TKA. TRIAL REGISTRATION NUMBER: NCT03834129.

Ciprofloxacin use in critically ill patients: pharmacokinetic and pharmacodynamic approaches.

The objective of this study was to evaluate the properties of ciprofloxacin in intensive care patients using a population approach. Seventy patients received ciprofloxacin. On Day 1, three to eight blood samples were taken over a 12-h period. Peak drug concentration (Cmax) and 24-h area under the concentration-time curve (AUC) were compared with the French breakpoint defining antibiotic susceptibility. A population pharmacokinetic modelling approach was then carried out. A two-compartment open model with a proportional error model best fitted the data. A relationship between the elimination constant rate and the Cockcroft creatinine clearance was found. Ciprofloxacin clearance was 13.6+/-5.8L/h, the volume of distribution was 62.0+/-10.7 L and the ciprofloxacin half-life was 3.7+/-1.8h. When the minimum inhibitory concentration (MIC) was equal to 1mg/L the inhibitory ratio (IR) was > or = 8 in only 10.8% of cases, and the AUC/MIC ratio (AUIC) was 42.0+/-36. In conclusion, this study highlights that the Cockcroft clearance significantly influences ciprofloxacin elimination. Target plasma concentrations for ciprofloxacin, the IR and AUIC were rarely reached with a standard dosing regimen. In critically ill patients, the observed pharmacokinetic variability is mainly responsible for the overly frequent low concentrations of ciprofloxacin, emphasising the need for therapeutic monitoring.