Background: Hypocalcemia is prevalent among critically ill patients requiring intensive care. Several epidemiological studies highlight a direct association between hypocalcemia and mortality. These data provide the impetus for current guidelines recommending parenteral calcium administration to normalize serum calcium. However, in light of the considerable variation in the threshold for calcium replacement, the lack of evidence to support a causal role of hypocalcemia in mortality, and animal studies illustrating that calcium supplementation may worsen outcomes, a systematic review is essential to evaluate whether or not the practice of calcium supplementation for intensive care unit (ICU) patients provides any benefit.
Objectives: To assess the effects of parenteral calcium administration in ICU patients on the following outcomes: mortality, multiple organ dysfunction, ICU and hospital length of stay, costs, serum ionized calcium concentration, and complications of parenteral calcium administration.
Search strategy: We searched The Cochrane Library, MEDLINE, EMBASE, Current Controlled Trials, and the National Research Register. We hand-searched conference abstracts from the Society of Critical Care Medicine, the European Society of Intensive Care Medicine, the American Thoracic Surgery, the American College of Surgeons, the American College of Chest Physicians, the American College of Physicians, and the International Consensus Conference in Intensive Care Medicine. We checked references of publications and attempted to contact authors to identify additional published or unpublished data.
Selection criteria: Randomised controlled and controlled clinical trials of ICU patients comparing parenteral calcium chloride or calcium gluconate administration with no treatment or placebo.
Data collection and analysis: Two reviewers independently applied eligibility criteria to trial reports for inclusion and extracted data.
Main results: There are no identifiable studies that have evaluated the association between parenteral calcium supplementation in critically ill ICU patients and the following outcomes: mortality, multiple organ dysfunction, ICU and hospital length of stay, costs, and complications of calcium administration. Serum ionized calcium concentration was reported in 5 studies (12 trial arms, 159 participants). These trials showed a small but significant increase in serum ionized calcium concentration after calcium administration. These trials showed considerable statistical heterogeneity and differed extensively in the population studied (adult versus neonate), the indication (hypocalcemia versus prophylaxis) and threshold of hypocalcemia for which parenteral calcium was administered, and the timing of subsequent measurement of serum ionized calcium concentration to the extent that we consider a pooled estimate almost inappropriate.
Authors' conclusions: There is no clear evidence that parenteral calcium supplementation impacts the outcome of critically ill patients.