Assessment and clinical course of hypocalcemia in critical illness

Abstract

IntroductionHypocalcemia is common in critically ill patients. However, its clinical course during the early days of admission and the role of calcium supplementation remain uncertain, and the assessment of calcium status is inconsistent. We aimed to establish the course of hypocalcemia during the early days of critical illness in relation to mortality and to assess the impact of calcium supplementation on calcium normalization and mortality.MethodsData were collected on 1,038 admissions to the critical care units of a tertiary care hospital. One gram of calcium gluconate was administered intravenously once daily to patients with adjusted calcium (AdjCa) <2.2 mmol/L. Demographic and outcome data were compared in normocalcemic (ionized calcium, iCa, 1.1-1.3 mmol/L) and mildly and severely hypocalcemic patients (iCa 0.9-1.1 mmol/L and <0.9 mmol/L, respectively). The change in iCa concentrations was monitored during the first four days of admission and comparisons between groups were made using Repeated Measures ANOVA. Comparisons of normalization and outcome were made between hypocalcemic patients who did and did not receive calcium replacement according to the local protocol. The suitability of AdjCa to predict low iCa was determined by analyzing sensitivity, specificity and receiver operating characteristic (ROC) curves. Multivariate logistic regression was performed to determine associations of other electrolyte derangements with hypocalcemia.Results55.2% of patients were hypocalcemic on admission; 6.2% severely so. Severely hypocalcemic patients required critical care for longer (P = 0.001) compared to normocalcemic or mildly hypocalcemic patients, but there was no difference in mortality between groups (P = 0.48). iCa levels normalized within four days in most, with no difference in normalization between those who died and survived (P = 0.35). Severely hypocalcemic patients who failed to normalize their iCa by day 4 had double the mortality (38% vs. 19%, P = 0.15). Neither iCa normalization nor survival were superior in hypocalcemic patients receiving supplementation on admission. AdjCa <2.2 mmol/L had a sensitivity of 78.2% and specificity of 63.3% for predicting iCa <1.1 mmol/L. Low magnesium, sodium and albumin were independently associated with hypocalcemia on admission.ConclusionsHypocalcemia usually normalizes within the first four days after admission to ICU and failure to normalize in severely hypocalcemic patients may be associated with increased mortality. Calcium replacement appears not to improve normalization or mortality. AdjCa is not a good surrogate of iCa in an ICU setting.

Implementation of Clinical Decision Support Rules to Reduce Repeat Measurement of Serum Ionized Calcium, Serum Magnesium, and N-Terminal Pro-B-Type Natriuretic Peptide in Intensive Care Unit Inpatients

“…Although hypocalcemia is common in septic and critically ill patients, it may result from a shift of calcium to the intracellular compartment and indicate disease severity without directly contributing to patient outcome (7 ). Furthermore, in critically ill patients with iCa values over 4.0 mg/dL (1.0 mmol/L), supplementation has not been shown to improve outcome (8 ).…”

Abnormal serum calcium levels are associated with clinical response to maximization of heart failure therapy

“…4 During the hyperadrenergic state, the calcium influx into cells is driven by catecholamines, aldosterone, and parathormone excess causing organellar dysfunction on one hand, and serum ionized hypocalcemia on the other. 5 The presence of hypocalcemia in acute hyperadrenergic conditions is a prognostically ominous sign, 6 while its correction with intravenous calcium was shown to be ineffective or even harmful. 6,7 According to the current guidelines, the hyperadrenergic state in HF should be inhibited by means of angiotensin-converting enzyme inhibitors (ACEIs), β-blockers, and aldosterone antagonists.…”

“…5 The presence of hypocalcemia in acute hyperadrenergic conditions is a prognostically ominous sign, 6 while its correction with intravenous calcium was shown to be ineffective or even harmful. 6,7 According to the current guidelines, the hyperadrenergic state in HF should be inhibited by means of angiotensin-converting enzyme inhibitors (ACEIs), β-blockers, and aldosterone antagonists. 8 These drugs have anticatabolic effects, and thereby may influence serum calcium levels.…”

Hypoparathyroidism in the Differential Diagnosis of Hypocalcemia

“…1 True hypocalcemia, defined by a low ionized serum calcium concentration, is far less common in patients than is a depressed serum total Ca ++ due to alterations in serum albumin or acid-base status. [2][3][4][5][6] For practical purposes, serum total Ca ++ can be used to assess for hypocalcemia in outpatients as long as serum albumin is concomitantly measured to allow for calculating albumin-adjusted serum total Ca ++ by the formulas in Table 47.1. 1,2 Serum total Ca ++ includes: ionized (45-50%); protein bound (45-50%); and anion-complexed (5-10%) fractions.…”