Evidence in Focus: Clinical Advances in Anesthesiology
Rafai Babar, MBBS
Robina Matyal, MD
Issue 3 | Volume 2 | August 2026
KEY TAKEAWAYS
- Emergency Intubation: Ketamine offered no survival advantage over etomidate and was associated with more cardiovascular collapse during intubation.
- Double Lumen intubation: Videolaryngoscopy improved first-pass success and reduced initial tube malposition without prolonging intubation time.
- Cancer Surgery: Propofol-based anesthesia did not improve survival or disease-free survival compared with volatile anesthesia, challenging a long-standing oncologic hypothesis.
- TAP blocks: Neither plain nor liposomal bupivicaine provided a significant analgesic advantage over saline, questioning routine use of this single-shot TAP-block strategy
Ketamine or Etomidate for Tracheal Intubation of Critically Ill Adults
doi:10.1056/NEJMoa2511420.
Ketamine and etomidate are commonly used for induction during emergency tracheal intubation, particularly when hemodynamic instability is a concern. Etomidate has traditionally been favored for cardiovascular stability but remains controversial because of adrenal suppression and concern that this might adversely affect outcomes in critically ill patients. Ketamine is frequently considered an alternative, in part because its sympathomimetic effects are thought to provide greater hemodynamic stability. This multicenter randomized trial directly compared the two agents in 2,365 critically ill adults undergoing emergency tracheal intubation across 14 emergency departments and intensive care units in the United States.
In-hospital mortality by day 28 (the primary outcome) did not differ significantly between ketamine and etomidate (28.1% vs. 29.1%; 95% CI, -4.5 to 2.9; P=0.65). Cardiovascular collapse during intubation, however, occurred more frequently with ketamine (22.1% vs. 17.0%; 95% CI, 1.9-8.3). Cardiovascular collapse was defined as systolic blood pressure <65 mmHg, initiation or escalation of vasopressor therapy, or cardiac arrest during the peri-intubation period.
The trial provides no evidence that choosing ketamine instead of etomidate improves survival in critically ill adults and challenges the assumption that ketamine is necessarily the more hemodynamically stable induction agent. The findings do not establish etomidate as the appropriate agent for every critically ill patient, but they provide strong randomized evidence against selecting ketamine solely on the expectation of superior cardiovascular stability during emergency intubation.
Commentary
This is the largest randomized comparison of ketamine and etomidate for emergency intubation and helps resolve uncertainty left by earlier trials. Matchett and colleagues randomized 801 critically ill patients at a single center and reported higher 7-day survival with ketamine than with etomidate (85.1% vs 77.3%; P=0.005), although the difference was no longer significant by day 28.¹ The present trial, nearly three times larger and conducted across 14 sites, found no mortality advantage with ketamine.
The cardiovascular-collapse signal may be more clinically informative. Ketamine’s sympathomimetic effects can support blood pressure, but this benefit may be less predictable in patients with severe physiologic stress or depleted catecholamine reserve. The current trial does not establish a specific mechanism for the higher collapse rate, and induction dose, baseline shock severity, vasopressor use, and pre-intubation optimization remain important potential modifiers. The practical message is therefore not that etomidate is universally preferable, but that ketamine should not be assumed to provide superior hemodynamic protection simply because the patient is critically ill. Recent pooled randomized evidence has reached a similar conclusion, showing comparable mortality but greater peri-intubation hemodynamic instability with ketamine.²
Videolaryngoscopy versus direct laryngoscopy for double-lumen tube intubation: the DOuble-Lumen intubation with VIdeolaryngoscopy (DOLVI) multicentre randomised trial
doi:10.1016/j.bja.2026.02.048.
The DOLVI trial compared videolaryngoscopy with direct laryngoscopy for double-lumen tube placement in 916 adults undergoing surgery requiring lung isolation at four hospitals. First-attempt intubation success (the primary outcome) was 84.7% with videolaryngoscopy compared with 76.9% with direct laryngoscopy, an absolute difference of 7.9 percentage points. Videolaryngoscopy also provided better glottic views and reduced airway manipulation, esophageal intubation, and initial tube malposition, without increasing intubation time.
These findings provide multicenter randomized evidence supporting videolaryngoscopy for double-lumen tube placement. The reduction in tube malposition is particularly relevant because it suggests that the advantage extends beyond improved visualization of the glottis to successful passage and positioning of a technically challenging airway device. The study was necessarily unblinded and was performed in centers experienced with videolaryngoscopy, and it was not powered to detect differences in uncommon complications such as airway injury or severe hypoxemia. Nevertheless, the improvement in first-pass success and multiple procedural outcomes supports videolaryngoscopy as a preferred initial approach to double-lumen intubation.
Commentary
The main challenge with videolaryngoscopy for double-lumen tubes is not obtaining a good view, but advancing and positioning a large, relatively rigid tube. DOLVI is therefore clinically useful because videolaryngoscopy reduced loss of glottic view during tube passage and initial tube malposition, suggesting an advantage beyond visualization alone. Airway trauma remains an important concern with double-lumen tubes, particularly after difficult or repeated manipulation.3,4 Although DOLVI was not powered to detect rare injuries such as tracheobronchial rupture, fewer attempts and fewer malpositions are directionally reassuring. Videolaryngoscopy also offers a practical teaching advantage by allowing the trainee and supervisor to share the same airway view.
Anesthesia Type during Cancer Surgery: Results of the GA-CARES Randomized, Multicenter Trial
doi:10.1097/ALN.0000000000005769.
GA-CARES tested whether propofol-based total intravenous anesthesia improves long-term oncologic outcomes compared with volatile anesthesia. The hypothesis had been supported by laboratory and observational studies suggesting that propofol might better preserve antitumor immunity. Patients undergoing resection of malignancies at relatively high risk of recurrence were randomized to propofol-based or volatile general anesthesia. In the intention-to-treat population of 1,763 patients, mortality was 26.1% with propofol and 22.9% with volatile anesthesia (HR, 1.16; 95% CI, 0.96-1.41; P=0.115). Disease-free survival was also not significantly different (HR, 1.10; 95% CI, 0.90-1.36). The trial therefore does not support choosing propofol-based anesthesia specifically to improve cancer survival or reduce recurrence. Mortality was higher with propofol in a secondary per-protocol analysis, but this should not be interpreted as evidence that propofol causes harm because exclusions occurring after randomization compromise the causal protection provided by randomization. GA-CARES is important because it subjects a biologically plausible hypothesis, previously supported predominantly by mechanistic and observational evidence, to a large randomized comparison and finds no oncologic advantage from propofol.
Commentary
This study builds on two previous randomized trials that found no oncologic advantage from propofol-based anesthesia. Sessler et al found no reduction in breast cancer recurrence with propofol-paravertebral anesthesia compared with sevoflurane-opioid anesthesia, while the CAN study found no difference in 5-year overall survival between propofol and sevoflurane.5,6 Both studies, however, involved breast cancer populations with relatively favorable prognoses and consequently low rates of recurrence and death.
GA-CARES addressed this limitation by enrolling patients with malignancies at higher risk of recurrence and mortality, providing more outcome events with which to detect a clinically meaningful difference. Despite this higher-risk population, propofol again provided no survival or disease-free survival benefit. Taken together, these randomized trials provide increasingly consistent evidence that anesthetic technique should not be selected on the expectation that propofol will reduce cancer recurrence or improve survival.
Liposomal Bupivacaine, Plain Bupivacaine, and Saline for Transversus Abdominis Plane Blocks: The CLEVELAND Randomized Trial
doi:10.1097/ALN.0000000000005869.
The CLEVELAND trial tested whether transversus abdominis plane (TAP) blocks provide meaningful analgesia after abdominal surgery and whether liposomal bupivacaine offers an advantage over conventional bupivacaine. Patients undergoing open and laparoscopic abdominal surgery were randomized to pre-incision bilateral four-quadrant TAP blocks with liposomal bupivacaine, plain bupivacaine, or saline. Among 261 patients in the modified intention-to-treat analysis, median opioid consumption during the first 24 hours was 26, 33, and 31 morphine milligram equivalents, respectively. Neither treatment significantly reduced opioid consumption compared with saline. Pain scores and opioid requirements during subsequent postoperative assessments were also similar.
The findings question the routine use of pre-incision, single-shot four-quadrant TAP blocks in a heterogeneous abdominal surgical population and provide no evidence of additional benefit from liposomal bupivacaine in this setting. The results should not be generalized to every application of TAP blockade: the surgical population was heterogeneous, all patients received multimodal analgesia, and the study did not evaluate continuous catheter techniques or procedure-specific approaches. Nevertheless, the inclusion of a saline control makes this an important reassessment of an intervention whose efficacy has often been inferred from comparisons between different local anesthetic formulations rather than against placebo.
Commentary
One question raised by CLEVELAND is whether block adjuvants might have produced a different result. Perineural dexamethasone and dexmedetomidine can prolong analgesia after peripheral nerve blocks, although most supporting evidence comes from conventional peripheral nerve blocks rather than fascial-plane techniques. Perineural dexamethasone provides only a modest prolongation compared with intravenous administration, while dexmedetomidine can extend analgesia but is associated with increased bradycardia and hypotension.
Whether either would improve the results of a TAP block remains uncertain. Adjuvants primarily prolong an effective block; CLEVELAND found no significant analgesic advantage of the underlying single-shot four-quadrant TAP technique over saline. The more important question raised by the trial is therefore not how to prolong the block, but whether this particular TAP-block strategy provides sufficient analgesic benefit to justify its routine use.
REFERENCES
- Matchett G, Gasanova I, Riccio CA, et al. Etomidate versus ketamine for emergency endotracheal intubation: a randomized clinical trial. Intensive Care Med. 2022;48(1):78-91. doi:10.1007/s00134-021-06577-x
- Zampieri FG, Schmidt RC, Besen BAMP, et al. Induction agents for emergency tracheal intubation in critically ill adults: a systematic review and network meta-analysis. Crit Care. 2026;30(1):296. Published 2026 May 12. doi:10.1186/s13054-026-06067-w
- Knoll H, Ziegeler S, Schreiber JU, et al. Airway injuries after one-lung ventilation: a comparison between double-lumen tube and endobronchial blocker: a randomized, prospective, controlled trial. Anesthesiology. 2006;105(3):471-477. doi:10.1097/00000542-200609000- 00009
- Liu S, Mao Y, Qiu P, Faridovich KA, Dong Y. Airway Rupture Caused by Double-Lumen Tubes: A Review of 187 Cases. Anesth Analg. 2020;131(5):1485-1490. doi:10.1213/ANE.0000000000004669
- Sessler DI, Pei L, Huang Y, et al. Recurrence of breast cancer after regional or general anaesthesia: a randomised controlled trial. Lancet. 2019;394(10211):1807-1815. doi:10.1016/S0140-6736(19)32313-X
- Enlund M, Berglund A, Enlund A, et al. Impact of general anaesthesia on breast cancer survival: a 5-year follow up of a pragmatic, randomised, controlled trial, the CAN-study, comparing propofol and sevoflurane. EClinicalMedicine. 2023;60:102037. Published 2023 Jun 9. doi:10.1016/j.eclinm.2023.102037
- Tan ESJ, Tan YR, Liu CWY. Efficacy of perineural versus intravenous dexamethasone in prolonging the duration of analgesia when administered with peripheral nerve blocks: a systematic review and meta-analysis. Korean J Anesthesiol. 2022;75(3):255-265. doi:10.4097/ kja.21390
- Vorobeichik L, Brull R, Abdallah FW. Evidence basis for using perineural dexmedetomidine to enhance the quality of brachial plexus nerve blocks: a systematic review and meta-analysis of randomized controlled trials. Br J Anaesth. 2017;118(2):167-181. doi:10.1093/bja/ aew41