Early versus deferred intravenous calcium in patients with sepsis and ionized hypocalcemia: a target-trial emulation
Authors' conclusion
Early intravenous calcium was associated with a higher probability of 24-h hemodynamic recovery than the deferred strategy, whose observed pathway involved no calcium through 24 h. Estimated effects were larger at higher vasopressor doses. Early calcium was associated with a modestly higher observed risk of hypercalcemia. These findings support randomized evaluation in vasopressor-treated patients. Baseline iCa modification remains exploratory.
Study context
- Population
- Adults with sepsis, final or corrected iCa of 0.90–1.10 mmol/L, and no emergency indication, Zigong Fourth People's Hospital electronic health records 2016–2025initiated calcium within 2 h 1,538 · initiated at 2-6 h 147 · received none through 6 h 4,308
- Participants
- 5,993 patients
- Exposure
- Calcium initiation within 2 h of a non-emergency low-ionized calcium (iCa) result and no calcium initiation during the first 6 h after the result
- Early calciumn = 1,538
- Deferraln = 4,308reference
- Outcome
- Being alive and vasopressor-free (24-h hemodynamic recovery)
- Follow-up
- 24 h
Methodological detailsclone-censor weighting, overlap tilting, 2,000 patient-level bootstrap samples with model refitting
- Clone-censor weighting
- Overlap tilting
- 2,000 patient-level bootstrap samples with model refitting
Main finding
As reported in the abstract
- Early calcium
- risk difference + 8.69 percentage points (95% percentile interval CI + 4.66 to + 12.84)
Observational data: associations, not effects.
Further findings
Effect modification by baseline norepinephrine-equivalent dose (subgroup)
- Effect modification by baseline norepinephrine-equivalent dose: The estimated association varied with baseline norepinephrine-equivalent dose
- Holm-adjusted P = 2.00 × 10⁻⁶
Effect modification by iCa (subgroup)
- Effect modification by iCa: the iCa interaction did not remain statistically supported after adjustment
- P = 0.097
Safety
| Outcome | Risk difference (higher with early calcium) (percentage points) (95% percentile interval CI) | |
|---|---|---|
| Hypercalcemia (observed risk) | 1.29 (+ 0.64 to + 2.05) | |
| −10123Difference, percentage points (linear scale) |
Severe arrhythmia, new renal replacement therapy, hospital mortality
- Intervals included the null
Original publication
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