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Meta-Analysis
. 2024 Dec 30;28(1):439.
doi: 10.1186/s13054-024-05212-7.

Non-adrenergic vasopressors for vasodilatory shock or perioperative vasoplegia: a meta-analysis of randomized controlled trials

Yuki Kotani  1 , Alessandro Belletti  2 , Filippo D'Amico  2 , Alessandra Bonaccorso  2 , Patrick M Wieruszewski  3   4 , Tomoko Fujii  5 , Ashish K Khanna  6   7 , Giovanni Landoni  2   8 , Rinaldo Bellomo  9   10   11   12   13   14
Affiliations
Meta-Analysis

Non-adrenergic vasopressors for vasodilatory shock or perioperative vasoplegia: a meta-analysis of randomized controlled trials

Yuki Kotani et al. Crit Care. .

Abstract

Background: Excessive exposure to adrenergic vasopressors may be harmful. Non-adrenergic vasopressors may spare adrenergic agents and potentially improve outcomes. We aimed to conduct a systematic review and meta-analysis of randomized controlled trials (RCTs) to evaluate the efficacy of non-adrenergic vasopressors in adult patients receiving vasopressor therapy for vasodilatory shock or perioperative vasoplegia.

Methods: We searched PubMed, Embase, and Cochrane Library for RCTs comparing non-adrenergic vasopressors with adrenergic vasopressors alone or placebo in critically ill or perioperative patients. Each eligible study was categorized into septic shock, cardiac surgery, or non-cardiac surgery. Non-adrenergic vasopressors included vasopressin, terlipressin, selepressin, angiotensin II, methylene blue, and hydroxocobalamin. The primary outcome was mortality at longest follow-up. We conducted a random-effects meta-analysis. We registered the protocol in PROSPERO International Prospective Register of Systematic Reviews (CRD42024505039).

Results: Among 51 eligible RCTs totaling 5715 patients, the predominant population was septic shock in 30 studies, cardiac surgery in 11 studies, and non-cardiac surgery in 10 studies. Cochrane risk-of-bias tool for randomized trials version 2 identified 17 studies as low risk of bias. In septic shock, mortality was significantly lower in the non-adrenergic group (960/2232 [43%] vs. 898/1890 [48%]; risk ratio [RR], 0.92; 95% confidence interval [95% CI], 0.86-0.97; P = 0.03; I2 = 0%), with none of the individual non-adrenergic vasopressors showing significant survival benefits. No significant mortality difference was observed in patients undergoing cardiac surgery (34/410 [8.3%] vs. 47/412 [11%]; RR, 0.82; 95% CI, 0.55-1.22; P = 0.32; I2 = 12%) or those undergoing non-cardiac surgery (9/388 [2.3%] vs. 18/383 [4.7%]; RR, 0.66; 95% CI, 0.31-1.41; P = 0.28; I2 = 0%).

Conclusions: Administration of non-adrenergic vasopressors was significantly associated with reduced mortality in patients with septic shock. However, no single agent achieved statistical significance in separate analyses. Although the pooled effects of non-adrenergic vasopressors on survival did not reach statistical significance in patients undergoing cardiac or non-cardiac surgery, the confidence intervals included the possibility of both no effect and a clinically important benefit from non-adrenergic agents. These findings justify the conduct of further RCTs comparing non-adrenergic vasopressors to usual care based on noradrenaline alone.

Keywords: Angiotensin II; Arginine vasopressin; Catecholamines; Meta-analysis; Methylene blue; Mortality.

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Conflict of interest statement

Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: Not applicable. Competing interests: YK has received consultancy fees from Viatris. PMW previously received consultant fees from Viatris. AKK received consulting fees from Medtronic, Edwards Life Sciences, Philips Research North America, Hillrom, GE Healthcare, Potrero Medical, Viatris Pharma, Trevena Pharma, Fifth Eye Inc., Pharmazz Inc., Retia Medical and Caretaker Medical. He is also funded with a Wake Forest Clinical and Translational Science Institute (CTSI) grant on renin dysfunction in septic shock. GL has received speaker fees from Medis, Paion, and Viatris and consultancy fees from Paion and Viatris. RB has received grants and consultancy fees from La Jolla Pharmaceuticals, Paion AG, and Viatris. The other authors have no competing interests.

Figures

Fig. 1
Fig. 1
Flow chart of study selection
Fig. 2
Fig. 2
Forest plot for mortality. A Septic shock. B Cardiac surgery. C Non-cardiac surgery
See this image and copyright information in PMC

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