Each 1-hour delay in mechanical ventilation initiation is associated with an increased risk of 30-day mortality.
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van Diepen S, Hochman JS, Stebbins A, Alviar CL, Alexander JH, Lopes RD. Association Between Delays in Mechanical Ventilation Initiation and Mortality in Patients With Refractory Cardiogenic Shock. JAMA Cardiol. 2020;5(8):965–967. doi:10.1001/jamacardio.2020.1274
Acute myocardial infarction (MI) is complicated by cardiogenic shock (CS) in 4% to 10% of patients, and contemporary mortality rates range from 31% to 51%.1 A common sequela of CS is an elevated end-diastolic pressure leading to pulmonary congestion, and mechanical ventilatory (MV) support is required in up to 88% of patients.2 Positive end-expiratory pressure (PEEP) imparts favorable cardiovascular hemodynamic changes in patients with CS and reduced left ventricular (LV) function. Positive end expiratory pressure lowers pulmonary wedge pressure, LV afterload, myocardial oxygen demand, work of breathing, and improves cardiac index and oxygenation.3 Consequently, the timely initiation of MV in this population could theoretically attenuate physiologic deterioration or the ischemic cascade and improve outcomes; however, to our knowledge, the association between timing of MV initiation and mortality in patients with CS has not been described.
The Tilarginine Acetate Injection in a Randomized International Study in Unstable MI Patients With Cardiogenic Shock (TRIUMPH) trial randomized patients with an MI with refractory CS to a nitric oxide synthase inhibitor or placebo.2 The study defined refractory CS as a systolic pressure less than 100 mm Hg despite moderate inopressor doses and hypoperfusion for at least 1 hour after revascularization. We used the time-stamped onsets of CS and invasive MV initiation to explore the association between timing of MV initiation relative to CS onset and 30-day mortality. Given the trial’s refractory CS definition, the analysis examined the association in the 24-hour window before and after CS. The adjusted odds ratio (OR) for mortality was determined by adjusting for available CARDSHOCK score variables (age, prior coronary artery bypass grafting, MI, LV ejection fraction, and systolic blood pressure) and baseline patient differences (body mass index). Ethics committees at all sites approved the study and written consent was obtained for all patients.2 All statistical tests were 2-sided, and a P value of less than .05 was considered statistically significant.
Among the 398 TRIUMPH trial participants, the study included 262 patients (65.8%) who received MV; 244 (93.1%) had MV initiated a median of 8.1 hours before the onset of refractory CS, and 18 (6.9%) had MV initiated a median of 17.8 hours after CS. Thirty-day mortality was 51.5%. Baseline differences were generally balanced (Table). Figure, A, shows each 1-hour delay in MV initiation was associated with higher 30-day morality (OR, 1.03; 95% CI, 1.00-1.06; P = .03), with a similar trend after multivariable adjustment (OR, 1.03; 95% CI, 1.00-1.06; P = .09). In a sensitivity analysis, each 1-hour delay in MV initiation from the time of MI onset (Figure, B) was independently associated with mortality (OR, 1.04; 95% CI, 1.01-1.06; P < .001).
Little is known about the optimal timing, modes, or ventilatory strategies in patients with CS, and this has been identified as a research need.1,3 When pulmonary edema is associated with reduced LV systolic function, PEEP has a number of theoretical cardiovascular benefits. Positive end-expiratory pressure can improve congestion by reducing venous return, increasing transmural pressure, and decreasing LV afterload; all of which can improve oxygenation, hypercapnia, and acidosis.3-5 Moreover, MV can reduce work of breathing and improve tissue perfusion, which, in conjunction with PEEP, can reduce myocardial oxygen consumption. We hypothesize these mechanisms may mediate the observed association with reduced mortality in patients with CS, and these physiological benefits could be augmented in an MI with CS prior to revascularization. We acknowledge the potential for confounding, the modest size, lack of hemodynamics, cardiac arrest, lactate, neurologic variables, or ventilation data in the study and that mechanical circulatory support with isolated LV dysfunction may obviate these benefits. Nevertheless, in a cohort of patients with refractory CS despite revascularization, we observed modest associations between mortality and delays in MV initiation from CS onset and from the time of MI. The potential physiologic and hemodynamic benefits of MV in patients with reduced LV systolic function and CS highlight the need for larger randomized studies into the optimal use of MV in this high-risk population.
Accepted for Publication: March 11, 2020.
Corresponding Author: Sean van Diepen, MD, MSc, 2C2 Cardiology Walter MacKenzie Center, University of Alberta Hospital; 8440-11 St, Edmonton, AB T6G 2B7, Canada (email@example.com).
Published Online: May 20, 2020. doi:10.1001/jamacardio.2020.1274
Author Contributions: Drs van Diepen and Lopes had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.
Concept and design: van Diepen, Hochman, Alviar, Alexander, Lopes.
Acquisition, analysis, or interpretation of data: van Diepen, Stebbins, Alexander, Lopes.
Drafting of the manuscript: van Diepen, Stebbins, Alviar, Lopes.
Critical revision of the manuscript for important intellectual content: Hochman, Alviar, Alexander, Lopes.
Statistical analysis: van Diepen, Stebbins.
Obtained funding: Alexander.
Administrative, technical, or material support: van Diepen, Hochman, Alexander.
Supervision: Hochman, Alviar, Alexander, Lopes.
Conflict of Interest Disclosures: Drs Alexander and Hochman are Principal Investigators for the ISCHEMIA trial for which, in addition to support by a National Heart, Lung, and Blood Institute grant, there were in-kind donations for participating sites from Abbott Vascular; Medtronic Inc; St. Jude Medical Inc; Volcano Corporation; Arbor Pharmaceuticals LLC; AstraZeneca Pharmaceuticals LP; Merck Sharp & Dohme Corp; Omron Healthcare Inc; and Amgen Inc and financial donations from Arbor Pharmaceuticals LLC and AstraZeneca Pharmaceuticals LP. Dr Alexander reported grants from VoluMetrix and Tenax outside the submitted work. Dr Lopes reported other support from Bayer and Boehringer Ingelheim, Merck, Daiichi Sankyo, and Portola and grants and other support from Bristol-Myers Squibb, GlaxoSmithKline, Medtronic, Pfizer, and Sanofi during the conduct of the study. No other disclosures were reported..
Funding/Support: This analysis was funded by the Duke Clinical Research Institute.
Role of the Funder/Sponsor: The funding source had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.
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