Daily Anesthesiology Research Analysis
A large pragmatic randomized trial found that adding ketamine to established ERAS pathways for major abdominal surgery did not improve outcomes and increased adverse effects, challenging routine use. A double-blind RCT showed remimazolam rapidly and safely controlled emergence agitation in the PACU. A multicenter cohort linking perioperative processes with claims data identified modifiable in-hospital opioid prescribing as a contributor to persistent postoperative opioid use.
Summary
A large pragmatic randomized trial found that adding ketamine to established ERAS pathways for major abdominal surgery did not improve outcomes and increased adverse effects, challenging routine use. A double-blind RCT showed remimazolam rapidly and safely controlled emergence agitation in the PACU. A multicenter cohort linking perioperative processes with claims data identified modifiable in-hospital opioid prescribing as a contributor to persistent postoperative opioid use.
Research Themes
- ERAS optimization and reconsideration of perioperative ketamine
- Management of emergence agitation with remimazolam
- Opioid stewardship to reduce persistent postoperative opioid use
Selected Articles
1. IMpact of PerioperAtive KeTamine on Enhanced Recovery After abdominal Surgery (IMPAKT ERAS): a pragmatic randomised single-cluster trial.
In a pragmatic double-blind randomized trial of 1,522 ERAS abdominal surgery patients, ketamine did not shorten hospital stay or reduce opioid use compared with placebo. Ketamine increased ICU transfers, hindered early discharge milestones, and led to more severe neuropsychiatric side effects. These data challenge routine ketamine use within ERAS pathways.
Impact: This large, well-conducted pragmatic RCT provides definitive evidence against routine perioperative ketamine in ERAS protocols and highlights harm signals.
Clinical Implications: Avoid routine ketamine in ERAS abdominal surgery pathways; prioritize multimodal regimens without ketamine and monitor for neuropsychiatric adverse effects if used.
Key Findings
- No reduction in hospital length of stay with ketamine versus placebo (adjusted OR 1.21; 95% CI 1.00–1.47).
- No significant reduction in opioid consumption (OR 0.85; 95% CI 0.71–1.01).
- Increased ICU transfers with ketamine (OR 2.03; 95% CI 1.14–3.63).
- Lower odds of meeting early discharge milestones with ketamine (OR 0.68; 95% CI 0.50–0.93).
- Higher rates of debilitating dizziness (OR 6.05) and hallucinations (OR 2.69) with ketamine.
Methodological Strengths
- Pragmatic, double-blind, placebo-controlled randomized design within an established ERAS program.
- Large sample size (n=1,522) with prespecified outcomes and adjusted analyses.
Limitations
- Single-cluster design may limit generalizability across diverse institutions.
- Trial tested a specific dosing and infusion strategy; other regimens were not evaluated.
Future Directions: Head-to-head trials of alternative multimodal analgesia without ketamine, subgroup analyses to identify patients at risk of ketamine adverse effects, and mechanistic studies on neuropsychiatric toxicity.
BACKGROUND: Despite widespread adoption of ketamine into enhanced recovery after surgery (ERAS) protocols, research regarding its specific impact on perioperative outcomes is limited. This pragmatic, randomised, double-blind, placebo-controlled, single-cluster trial evaluated the impact of ketamine on postoperative outcomes in patients undergoing major abdominal surgery within an established ERAS protocol. METHODS: Male and female patients, aged ≥18 yr, were randomised to ketamine or saline placebo bolus at induction of general anaesthesia, followed by an intraoperative and postoperative infusion for 48 h. The primary outcome was hospital length of stay. Secondary outcomes included total opioid consumption and the incidences of side-effects and adverse events. RESULTS: A total of 1522 patients were included. In covariate adjusted analyses, ketamine administration did not decrease length of stay (odds ratio [OR] 1.21; 95% confidence interval [CI] 1.00-1.47) or opioid consumption (OR 0.85; 95% CI 0.71-1.01) compared with placebo. Patients receiving ketamine experienced higher odds of ICU transfer (OR 2.03; 95% CI 1.14-3.63) and lower odds of meeting early discharge milestones (OR 0.68; 95% CI 0.50-0.93). Rapid response activation (OR 1.51; 95% CI 0.85-2.68) and ileus requiring nasogastric decompression (OR 1.26; 95% CI 0.87-1.84) were similar between groups. Patients receiving ketamine experienced higher rates of debilitating dizziness (OR 6.05; 95% CI 3.02-12.11), debilitating hallucinations (OR 2.69; 95% CI 1.09-6.65), and other severe side-effects (OR 1.94; 95% CI 1.27-2.96). CONCLUSIONS: The addition of ketamine to a multimodal abdominal ERAS protocol provided no significant benefits and was associated with worse perioperative outcomes. CLINICAL TRIAL REGISTRATION: NCT04625283.
2. The efficacy and safety of remimazolam for the management of emergence agitation: a randomized, double-blind, placebo-controlled study.
In adults with PACU emergence agitation after otolaryngological surgery, remimazolam 2.5 mg or 5.0 mg significantly improved treatment success versus placebo within 15 minutes. The 2.5 mg dose offered an efficacy–safety balance, while 5.0 mg may be preferable for dangerous agitation.
Impact: Provides randomized, blinded evidence for a fast-acting benzodiazepine option to control emergence agitation, a common and hazardous PACU problem.
Clinical Implications: Consider low-dose remimazolam (2.5 mg) as first-line pharmacologic management for PACU emergence agitation, with 5.0 mg reserved for severe agitation; monitor recovery profile and hemodynamics.
Key Findings
- Treatment success within 15 minutes was higher with remimazolam 2.5 mg (77.5%) and 5.0 mg (85.9%) than placebo (44.3%).
- Secondary outcomes indicated reduced need for rescue propofol and shorter EA duration with remimazolam (details per study).
- The 2.5 mg dose balanced efficacy and safety; 5.0 mg favored in dangerous agitation.
Methodological Strengths
- Randomized, double-blind, placebo-controlled design with objective SAS-based endpoint.
- Dose–response assessment enabling clinical dosing guidance.
Limitations
- Single surgical specialty (otolaryngology) limits generalizability across procedures.
- Short-term PACU outcomes; no long-term neurocognitive follow-up.
Future Directions: Multicenter trials across diverse surgeries, head-to-head comparisons with standard agents, and evaluation of impacts on PACU throughput and safety.
INTRODUCTION: Emergence agitation (EA) is a common postoperative complication characterized by confusion, disorientation, and restless behavior that can lead to self-harm, the removal of medical devices, and other adverse events. This randomized, double-blind, placebo-controlled study was designed to assess the efficacy and safety of a novel benzodiazepine, remimazolam, in the management of EA. METHODS: A total of 219 adults experienced EA (Riker Sedation-Agitation Scale SAS score ≥5) after otolaryngological surgery were randomly assigned (1:1:1 ratio) to receive one of the following three treatments: 2.5 mg remimazolam, 5.0 mg remimazolam, or placebo. The primary endpoint was the treatment success rate of EA, which was defined as an SAS score of <5 within 15 min after administration without the need for rescue sedation and no recurrence after 15 min. Secondary outcomes included rescue propofol dosage, EA duration, and the post-anesthesia care unit (PACU) discharge time. Adverse events were also monitored. RESULTS: Both remimazolam groups (77.5% for 2.5 mg and 85.9% for 5.0 mg) had significantly higher treatment success rates compared to the placebo group (44.3%) (both DISCUSSION: Our findings suggest that remimazolam is a promising option for managing EA in the PACU. For the entire study population, the 2.5 mg dose strikes an optimal balance between efficacy and safety. In patients with dangerous agitation, a 5.0 mg dose of remimazolam may offer potential benefits. These findings hold significant implications for guiding future therapeutic strategies for EA. CLINICAL TRIAL REGISTRATION: https://www.chictr.org.cn/, identifier ChiCTR2400085903.
3. How perioperative processes and patient-reported outcomes contribute to persistent postoperative opioid use: A cohort study linking clinical and health claims data.
Linking a national pain registry with claims data across 31 hospitals, PPOU occurred in 7.8% of surgical patients. In-hospital opioid administration, especially on the ward, increased the adjusted absolute risk by 4%, while higher day-1 pain scores increased and postoperative nausea decreased risk. Preadmission opioid use and depression were dominant patient-level risks.
Impact: Identifies modifiable, clinician-controlled drivers of PPOU using real-world linked data, informing immediate changes in perioperative opioid stewardship.
Clinical Implications: Minimize routine ward opioid prescribing, prioritize multimodal non-opioid analgesia, and proactively manage high pain scores while screening for depression and preadmission opioid use.
Key Findings
- Persistent postoperative opioid use occurred in 7.8% of patients across 31 hospitals.
- In-hospital opioid administration increased adjusted absolute PPOU risk by 4%, especially opioids prescribed on the ward.
- Preadmission opioid use (aOR 20.8) and depression (aOR 1.85) were strong patient-level risk factors.
- Higher day-1 maximal pain increased absolute PPOU risk (0.5% per NRS point), while postoperative nausea decreased it (−2.6%).
Methodological Strengths
- Prospective multicenter cohort linking detailed perioperative data with objective claims outcomes.
- Use of patient-reported outcomes and adjusted models to quantify absolute risk changes.
Limitations
- Observational design susceptible to residual confounding despite adjustments.
- Findings from German hospitals and insurance data may limit generalizability.
Future Directions: Interventional studies testing ward-level opioid minimization strategies and integration of PRO-guided pain management to reduce PPOU.
BACKGROUND: Opioid analgesics play a major role in perioperative pain management, yet their use can lead to persistent postoperative opioid use (PPOU), with significant societal and health costs. Patient-specific risk factors of PPOU are well described but little is known about factors that can be controlled by clinicians. OBJECTIVES: To find PPOU risk factors among perioperative processes and pain-related patient-reported outcomes (PROs) on the first postoperative day. DESIGN: Prospective cohort study linking perioperative data from Quality Improvement in Postoperative Pain Treatment (QUIPS) pain registry with health claims data from BARMER insurance. SETTING: Thirty-one German hospitals in 2021. PATIENTS: We analysed 1849 of 1994 patients undergoing surgery (mean age = 61.6 years ± 17.3, 60.7% women). Exclusion criteria: under 18 years, unable to communicate, not consenting, failed data linkage. MAIN OUTCOME MEASURE: Persistent postoperative opioid use (PPOU), defined as at least one opioid prescription within 90 days postdischarge and another one between days 91 and 180. RESULTS: Overall, 7.8% of patients showed PPOU. In logistic regression models, preadmission opioid use, adjusted odds ratio (aOR) = 20.8, P < 0.001, and depression, aOR = 1.85, P = 0.006, were patient-specific risk factors. Opioid administration during the hospital stay was associated with 4% increase in adjusted absolute PPOU risk ( P = 0.001), with opioids on the ward standing out. Among PROs on the first postoperative day, higher maximal pain intensity (0.5% per point on 11-point Numeric Rating Scale, P = 0.023) was associated with an increased absolute PPOU risk while postoperative nausea (2.6% if yes, P = 0.034) was associated with a decreased absolute risk. CONCLUSIONS: Perioperative opioids significantly contributed to the risk of PPOU, emphasising the need for careful opioid management postsurgery. Addressing pain effectively and promptly, while minimising opioid prescriptions on the ward, may reduce PPOU. Further research is needed to refine pain management and optimise patient outcomes.