Parenteral calcium for intensive care unit patients

 

Abstract

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 methods

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 We checked references of publications and attempted to contact authors to identify additional published or unpublished data.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.

 

Plain language summary

Parenteral calcium for intensive care unit patients

Several epidemiological studies of critically ill patients highlight a direct association between low levels of calcium (hypocalcemia) and mortality, though whether this association is causal is unknown. On the other hand, despite prior studies detailing associations between hypocalcemia and poor outcome, there is evidence to suggest that calcium supplementation in critical illness may be deleterious. Five randomized controlled trials with 159 participants were detected. All of the five included studies were conducted in the USA. No trial evaluated the association between parenteral calcium supplementation in critically ill intensive care unit patients and the following outcomes: mortality, multiple organ dysfunction, intensive care unit and hospital length of stay, costs, and complications of calcium administration. Some data on laboratory measurements (serum calcium) could be extracted. Nonetheless, these data provide little to guide the care of intensive care unit patients. The question of greater importance, "Does correcting hypocalcemia in critically ill patients provide any benefit in reducing mortality, the development of organ dysfunction, or the allocation of resources ?" remains to be answered. At present, the evidence base for guidelines regarding calcium administration in intensive care unit patients is poor.

 

摘要

背景

以注射補充加護病房患者之鈣離子

低鈣血症對加護病房照護的重症病人來說是普遍的問題。一些流行病學研究強調低鈣血症和死亡率間的直接相關性。這些資料促使現行臨床指引建議使用注射鈣(parenteral calcium)來矯正低血鈣。然而，鑑於應補充血鈣之閾值相當分歧、缺乏證據支持低鈣血症與死亡之因果關係、以及動物實驗發現補充鈣可能有害，以系統性回顧評估補充加護病房患者之血鈣是否對患者有益是有必要的。

目標

以下列結果評估鈣之補充對加護病房患者之治療成效：死亡率，多重器官功能不全(dysfunction)，加護病房及住院天數，醫療費用，血清離子鈣的濃度，以及鈣離子注射之併發症。

搜尋策略

我們搜尋了The Cochrane Library，MEDLINE，EMBASE，Current Controlled Trials和the National Research Register。我們也以人工搜尋急重症醫學會(Society of Critical Care Medicine),歐洲加護醫學會(the European Society of Intensive Care Medicine), 美國胸腔外科學會(the American Thoracic Surgery), 美國外科學會(the American College of Surgeons), 美國胸腔內科學會(the American College of Chest Physicians), 美國醫師學會(the American College of Physicians), 和國際重症加護醫學共識會議(the International Consensus Conference in Intensive Care Medicine) 之會議摘要。我們也搜尋已出版資料之參考文獻，聯繫其作者，以確定是否有其他更多已出版或未出版的數據。

選擇標準

比較加護病房病人接受注射氯化鈣或葡萄糖酸鈣、和沒有治療或給安慰劑之臨床效果的隨機對照實驗(Randomised controlled trials)以及臨床對照實驗(controlled clinical trials)。

資料收集與分析

兩個審查者對研究報告各自獨立判斷是否選入及擷取此報告之研究數據

主要結論

沒有研究評估以注射方式補充鈣和加護病房患者的結果指標的相關性，包括以下：死亡率、多器官功能不全、加護病房及總住院天數、醫療費用、以及給予鈣離子的併發症。有五篇研究有血清離子鈣濃度之報告(12研究分項，159受試者)。這些試驗顯示在注射鈣之後血清離子鈣濃度有小幅度但可明顯發現之增加。但這些試驗在統計資料上顯示相當之異質性，包括受試者組成(成人與新生兒)、對於鈣離子補充之目的(治療低鈣血症或是預防低血鈣)、注射鈣離子之低血鈣閾值以及隨後測量血清離子鈣濃度之時間都相當不一致，因此我們認為將這些結果放在一起評估是不恰當的。

作者結論

沒有明確的證據證明以注射方式補充鈣會影響急重症患者之治療結果。

翻譯人

本摘要由慈濟醫院謝至鎠翻譯。

此翻譯計畫由臺灣國家衛生研究院(National Health Research Institutes, Taiwan)統籌。

總結

注射鈣對加護病房患者之療效：數個流行病學研究強調加護病房患者低鈣血症和死亡率間有直接相關性，但此關聯性是否有因果關係則不能確定。另一方面，儘管先前的研究顯示低鈣血症和預後不佳之關聯，仍然有證據證明，鈣之補充對重症患者可能有害。我們找到5個隨機對照試驗共159人參與。五個研究都是在美國進行。沒有研究評估以注射補充鈣對加護病房患者之死亡率，多器官功能不全，加護病房及總住院天數，醫療費用，以及鈣離子注射補充併發症之影響。其中一些血清鈣數據可以提供參考，但這些數據在照顧重症加護病房患者時幾無用處。對於〝重症之患者，矯正其低血鈣是否能夠在降低死亡率、減少器官功能不佳或醫療資源之分配上有任何助益？〞這個重要的問題仍然無法回答。現行醫療準則建議在加護病房患者低血鈣時需補充鈣之實證基礎不佳。