Serious Adverse Events Associated With Vasopressin and Norepinephrine Infusion in Septic Shock*
Bibliographic record
Abstract
OBJECTIVE: The frequency, risk factors, and mortality rates of serious adverse events associated with the use of vasopressin and norepinephrine are not clear. The objectives of this study were to determine frequency, risk factors (including candidate gene polymorphisms), and outcomes of serious adverse events in septic shock patients. DESIGN: Retrospective cohort study using multicenter discovery and single-center validation cohorts. SETTING: ICUs at academic teaching centers. PATIENTS: Five hundred ninety-seven patients with septic shock in discovery (Vasopressin and Septic Shock trial) and 533 patients in validation (St. Paul's Hospital) cohorts. INTERVENTION: Vasopressin and norepinephrine for septic shock. MEASUREMENTS AND MAIN RESULTS: The primary outcome variable was 90-day mortality rates of patients with and without serious adverse events. Secondary outcome variables were the association between vasopressor genotype pathway polymorphisms, plasma vasopressin levels, and serious adverse events. Plasma vasopressin concentrations were measured at baseline, 6 hours, 24 hours, 72 hours, and 7 days after vasopressor infusion. Patients with septic shock were genotyped for 268 vasopressor pathway tag single-nucleotide polymorphisms. Serious adverse events occurred in 10.5% and 9.7% of patients in Vasopressin and Septic Shock trial and St. Paul's Hospital cohorts, respectively. Patients who had serious adverse events had higher mortality (p < 0.01) than patients without serious adverse events (adjusted for age, serum lactate, Acute Physiology and Chronic Health Evaluation II, and maximum dose of norepinephrine day 1) (hazard ratio, 2.97; 95% CI, 2.20-4.00; p < 0.001 and hazard ratio, 1.89; 95% CI, 1.26-2.85; p = 0.002 in Vasopressin and Septic Shock trial and St. Paul's Hospital, respectively). There was no difference in the area under the plasma vasopressin concentration curve between patients with and without serious adverse events (p = 0.1). The AA genotype of rs28418396 single-nucleotide polymorphism (near the arginine vasopressin receptor 1b gene) was significantly associated with serious adverse events in discovery and validation cohorts (p = 0.001 and p = 0.04, respectively). CONCLUSION: Serious adverse events associated with vasopressin and norepinephrine in patients who have septic shock are associated with increased mortality and morbidity. AA genotype of rs28418396 single-nucleotide polymorphism near the arginine vasopressin receptor 1b gene is associated with serious adverse events. The mechanism of this association requires investigation.
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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 | 0.000 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
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".