Dysregulated serum chloride and clinical outcomes in critically ill adults: A systematic review and meta-analysis
Bibliographic record
Abstract
Dysregulated serum chloride levels are prevalent in critically ill patients. However, their clinical impact remains unclear. This first systematic review and meta-analysis quantified the prevalence of hypochloremia and hyperchloremia, and their associations with mortality and acute kidney injury (AKI) in critically ill populations. We searched PubMed, Embase, Web of Science, and the Cochrane Library for studies reporting hyperchloremia prevalence or outcomes in adult ICU patients until August 2025. Statistical analyses were conducted using Stata v16.0, and study quality was assessed using the Newcastle-Ottawa Scale. 34 studies (n = 175,021 patients) were included. The aggregated prevalence of hyperchloremia was 34% (95% CI [26%-43%]) and hypochloremia was 14% (95% CI [1%-28%]). Meta-analysis demonstrated that both hyperchloremia and hypochloremia were significantly associated with increased mortality, conferring a 28% (OR = 1.28, 95% CI [1.08-1.52]) and 55% (OR = 1.55%, 95% CI [1.33-1.81]) elevated risk for mortality, respectively. Crucially, a dose-response analysis revealed a non-linear relationship between serum chloride levels and mortality, confirming that the risk is independently elevated at both extremes. Furthermore, hyperchloremia was linked to an increased risk of AKI (OR = 1.40, 95% CI [1.07-1.85]). These findings establish dysregulated serum chloride as a common and clinically significant biomarker, underscoring the necessity of monitoring and managing both high and low chloride levels in critically ill patients. Future large-scale studies are warranted to validate these results and elucidate the mechanistic pathways linking chloride dysregulation to such adverse outcomes.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.009 | 0.021 |
| Meta-epidemiology (narrow) | 0.003 | 0.001 |
| Meta-epidemiology (broad) | 0.017 | 0.034 |
| Bibliometrics | 0.005 | 0.007 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.003 | 0.001 |
| Open science | 0.002 | 0.001 |
| Research integrity | 0.002 | 0.002 |
| Insufficient payload (model declined to judge) | 0.003 | 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 source (direct Gemma or distilled Codex), 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".