Fellow physician University of Louisville Louiville, Kentucky, United States
Disclosure(s):
Angela khidhir, DO, MSc: No financial relationships to disclose
Background: Shock in the intensive care unit is traditionally classified by a single presumed cause, yet patients frequently exhibit overlapping physiology. These mixed distributive and cardiogenic shock states remain poorly characterized. We aimed to define the prevalence, physiologic severity, and outcomes of mixed shock using a large real-world multicenter dataset.
Methods: We conducted a retrospective cohort study using the TriNetX Global Collaborative Network that included adult ICU patients receiving vasopressor therapy. Patients were classified into three mutually exclusive shock phenotypes: sustained vasoplegic shock (vasopressor use without inotropes), mixed shock (concurrent vasopressor and inotrope use), and refractory shock (≥2 vasopressors required). Postcardiotomy patients were excluded. Propensity score matching (1:1 nearest-neighbor) was performed to compare mixed shock and sustained vasoplegic shock, balancing for age, sex, heart failure, ischemic heart disease, chronic kidney disease, acute kidney injury, and serum lactate. The primary outcome was ICU mortality. Secondary outcomes included physiologic severity, initiation of continuous renal replacement therapy, and utilization of mechanical circulatory support. Refractory shock was analyzed as a severity anchor rather than a post-index exposure.
Outcome: Among 138,518 ICU patients with shock, sustained vasoplegic shock accounted for 31,109 (22%), mixed shock for 106,409 (77%), and refractory shock for 1,298 (1%). After propensity score matching, 32,010 patients remained in each of the mixed- and vasoplegic-shock cohorts, with excellent covariate balance. Mixed shock was associated with significantly higher serum lactate compared with sustained vasoplegic shock (2.49 ± 3.22 vs 1.70 ± 2.10 mmol/L, p < 0.001), reflecting greater physiologic derangement. ICU mortality was significantly higher in mixed shock than vasoplegic shock (36.9% vs 31.3%; absolute risk difference 5.6%; risk ratio [RR] 1.18, 95% CI 1.15–1.20; p < 0.001). Continuous renal replacement therapy was initiated more frequently in mixed shock compared with vasoplegic shock (1.3% vs 0.9%; RR 1.38, 95% CI 1.19–1.60; p < 0.001). Use of mechanical circulatory support was infrequent and did not differ significantly between phenotypes (0.09% vs 0.12%; RR 0.81, 95% CI 0.50–1.31; p = 0.39). Refractory shock demonstrated the highest mortality, consistent with progressive shock severity.
Conclusion: Mixed shock dominates contemporary ICU practice and carries higher mortality, greater physiologic severity, and increased renal support needs versus vasoplegic shock. These findings reveal limitations of single-etiology classifications and highlight the need for earlier recognition and targeted management of mixed shock states.
