Low-Dose Esketamine Preserves Discharge Readiness and Reduces Propofol Consumption in Outpatient Bronchoscopy
核心洞察
Adding low-dose esketamine (0.1 or 0.2 mg/kg) to propofol sedation met non-inferiority criteria for discharge readiness within 30 minutes in a 246-patient randomized trial.
Both esketamine doses significantly reduced total propofol consumption by 20% and 28%, respectively, and lowered intraoperative cough severity.
Esketamine at 0.2 mg/kg was associated with significantly lower rates of hypotension (12% vs 51%) and hypoxemia (4% vs 21%) compared with propofol alone.
A randomized, double-blind, non-inferiority trial conducted at Fujian Provincial Hospital in China has demonstrated that supplementing propofol with low-dose esketamine preserves timely discharge readiness while reducing propofol requirements and improving cardiorespiratory stability during outpatient flexible bronchoscopy. The findings, published in Drug Design, Development and Therapy, address a key operational concern: whether esketamine, an NMDA receptor (搜索) antagonist with analgesic and sympathomimetic properties, would delay recovery in time-sensitive ambulatory settings.
The trial enrolled 246 adults aged 18 to 75 years with ASA physical status I–III who were scheduled for elective outpatient flexible bronchoscopy. Participants were randomly assigned in a 1:1:1 ratio to receive propofol plus 0.9% saline (propofol-alone group), propofol plus esketamine at 0.1 mg/kg, or propofol plus esketamine at 0.2 mg/kg.
Non-Inferiority Met for Discharge Readiness
The primary endpoint was the proportion of participants achieving discharge readiness within 30 minutes of procedure completion, defined as a Modified Post-Anesthetic Discharge Scoring System (MPADSS) score of 9 or higher. Both esketamine doses met the prespecified non-inferiority criterion with a margin of −18 percentage points.
In the intention-to-treat analysis, the risk difference compared with propofol alone was −3.0 percentage points (95% CI, −13.8 to 7.8; Pnon-inferiority = 0.003) for the 0.1 mg/kg dose and −5.1 percentage points (95% CI, −16.2 to 6.1; Pnon-inferiority = 0.012) for the 0.2 mg/kg dose. Per-protocol analyses were consistent, and all 232 per-protocol participants met discharge criteria within 40 minutes. Kaplan–Meier analysis showed comparable time-to-discharge curves across groups, with Cox hazard ratios of 0.93 (95% CI, 0.69–1.27) and 0.84 (95% CI, 0.62–1.14) for the 0.1 and 0.2 mg/kg doses, respectively.
Reduced Propofol Consumption and Improved Hemodynamics
Total propofol consumption was significantly lower in both esketamine groups: 200 mg (IQR 160–240) with 0.1 mg/kg and 180 mg (IQR 150–210) with 0.2 mg/kg, compared with 250 mg (IQR 215–300) in the propofol-alone group (both P < 0.001), representing relative reductions of 20% and 28%, respectively.
Hypotension occurred in 42 participants (51%) in the propofol-alone group, compared with 24 (29%) in the 0.1 mg/kg group (P = 0.007) and 10 (12%) in the 0.2 mg/kg group (P < 0.001). The incidence of hypoxemia was significantly lower with esketamine 0.2 mg/kg: 3 participants (4%) versus 17 (21%) in the propofol-alone group (P = 0.002). The 0.1 mg/kg group showed an intermediate hypoxemia rate of 10 participants (12%; P = 0.206 versus propofol alone).
Cough Severity and Patient Experience
Intraoperative cough severity was reduced in both esketamine groups compared with propofol alone (P = 0.005 and P = 0.002, respectively). Injection-site pain scores were also lower with both esketamine doses. Patient satisfaction was significantly higher in the 0.2 mg/kg group (P = 0.014). No significant differences were observed in emergence time, bronchoscopist satisfaction, or willingness to undergo repeat bronchoscopy.
Recovery Quality and Safety
Recovery quality, assessed using the Postoperative Quality of Recovery Scale (PostopQRS) across five domains at 30 minutes, 24 hours, and 72 hours, showed no significant group-by-time interactions, indicating comparable recovery trajectories. Rates of hypertension, bradycardia, tachycardia, postoperative nausea and vomiting, and neuropsychiatric effects did not differ significantly between groups.
Clinical Implications and Limitations
The authors note that these results contrast with earlier studies using racemic ketamine at higher doses, which reported prolonged recovery. Esketamine's approximately twofold greater NMDA receptor (搜索) affinity allows effective analgesia at lower doses while minimizing psychomimetic and sedative effects that delay discharge.
The single-center design and exclusion of patients with obstructive sleep apnea–hypopnea syndrome, significant neurological disease, or ASA physical status IV or higher limit generalizability. The sample size was calculated for the primary endpoint, potentially leaving the study underpowered for some secondary outcomes. P values for secondary endpoints were not adjusted for multiple comparisons, and the authors emphasize that findings beyond discharge readiness should be regarded as hypothesis-generating.
Future research should examine esketamine–propofol combinations during more complex bronchoscopic procedures and include head-to-head comparisons with other adjuncts such as remifentanil or dexmedetomidine, with adequate power for safety endpoints and longer-term neurocognitive follow-up.