The role of inotropes in cardiogenic shock: to help, to harm or do nothing at all?
Bibliographic record
Abstract
Cardiogenic shock (CS) is characterized by low cardiac output, resulting in end-organ hypoperfusion. Despite therapeutic advances, mortality remains high at upwards of 40%.1 Current guidelines recommend consideration of inotropes in patients with CS, with purported benefits of augmented cardiac output and contractility, improved lusitropy, and reduced afterload through vasodilation of the systemic and pulmonary circulations.1 In the first head-to-head comparison of inotrope therapy in CS, our research group demonstrated no difference in clinical outcomes between milrinone and dobutamine.2 While inotropes are widely used, uncertainties remain regarding their safety and efficacy in CS. A recent network meta-analysis evaluating the relative efficacy of inotropes in CS showed that milrinone and dobutamine may have no effect on mortality compared with placebo; however, the low certainty evidence does not rule out the possibility of benefit or harm.3 Trials to date have been limited by the enrolment of patients with pre-shock, predominantly SCAI class A and/or B, limiting generalizability.3,4 Moreover, inotrope therapy has been associated with a concerning signal of harm, including prolonged intensive care unit and hospital stays and increased in-hospital mortality among decompensated heart failure patients.5 Finally, no randomized trials have yet investigated the efficacy of single-agent inotrope therapy against placebo in the initial resuscitation of patients with CS, a significant gap in the current literature. The CAPITAL DOREMI2 trial is a multi-centre, randomized controlled trial comparing single-agent inotrope therapy against placebo in patients with SCAI class C–D CS. This trial will be the first of its kind to establish the safety and efficacy of inotrope therapy during the initial resuscitation of patients with CS, carrying the potential to change the standard care. A total of 346 participants will be randomized to single inotrope or placebo therapy for up to 12 h. Participants will then continue open-label therapies at the discretion of the treating team and be followed for the duration of their index hospitalization. Primary and secondary outcomes are detailed in Table 1. Study recruitment commenced in March 2022, and we have successfully enrolled 159 patients (46% of the total study cohort). The trial is anticipated to recruit participants over a 3-year period, with additional sites across North America currently in the process of starting recruitment. Primary and secondary outcomes in CAPITAL DOREMI2 In summary, little evidence exists to support the use of inotrope therapy in CS. The CAPITAL DOREMI2 trial aims to establish the safety and efficacy of inotrope therapy compared to placebo in patients with CS, holding the potential to reshape the standard care provided to this population. The data underlying this article will be shared on reasonable request to the corresponding author. Conflict of interest: The authors have no conflict of interest to declare.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.004 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.000 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".