Calcium Administration Is Associated with Adverse Outcomes in Critically Ill Patients Receiving Parenteral Nutrition: Results from a Natural Experiment Created by a Calcium Gluconate Shortage

Dotson, Bryan; Larabell, Patrick; Patel, Jasmine; Wong, Kristoffer; Qasem, Lina; Arthur, William; Leiberman, Chaim; Whittaker, Peter; Tennenberg, Steven D.

doi:10.1002/phar.1849

Cited by 20 publications

(19 citation statements)

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“…However, a systematic review of adult literature found no evidence to support treating hypocalcemia of critical illness [350]. Calcium supplementation may actually worsen organ dysfunction and is correlated with adverse outcomes in critically ill adult patients receiving PN [351]. Although the prevalence of hypocalcemia in critically ill children has been reported to be up to 75% and is associated with organ dysfunction [352], no studies in children with septic shock have investigated the effect of calcium supplementation to treat hypocalcemia.…”

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confidence: 99%

Surviving sepsis campaign international guidelines for the management of septic shock and sepsis-associated organ dysfunction in children

et al. 2020

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Objectives: To develop evidence-based recommendations for clinicians caring for children (including infants, school-aged children, and adolescents) with septic shock and other sepsis-associated organ dysfunction.Design: A panel of 49 international experts, representing 12 international organizations, as well as three methodologists and three public members was convened. Panel members assembled at key international meetings (for those The Society of Critical Care Medicine guidelines are intended for general information only, are not medical advice, and do not replace professional advice, which should be sought for any medical condition. The full disclaimer for guidelines can be accessed at https ://www.sccm.org/Resea rch/Guide lines /Guide lines . panel members attending the conference), and a stand-alone meeting was held for all panel members in November 2018. A formal conflict-of-interest policy was developed at the onset of the process and enforced throughout. Teleconferences and electronic-based discussion among the chairs, co-chairs, methodologists, and group heads, as well as within subgroups, served as an integral part of the guideline development process. Methods:The panel consisted of six subgroups: recognition and management of infection, hemodynamics and resuscitation, ventilation, endocrine and metabolic therapies, adjunctive therapies, and research priorities. We conducted a systematic review for each Population, Intervention, Control, and Outcomes question to identify the best available evidence, statistically summarized the evidence, and then assessed the quality of evidence using the Grading of Recommendations Assessment, Development, and Evaluation approach. We used the evidence-to-decision framework to formulate recommendations as strong or weak, or as a best practice statement. In addition, "in our practice" statements were included when evidence was inconclusive to issue a recommendation, but the panel felt that some guidance based on practice patterns may be appropriate. Results:The panel provided 77 statements on the management and resuscitation of children with septic shock and other sepsis-associated organ dysfunction. Overall, six were strong recommendations, 49 were weak recommendations, and nine were best-practice statements. For 13 questions, no recommendations could be made; but, for 10 of these, "in our practice" statements were provided. In addition, 52 research priorities were identified. Conclusions:A large cohort of international experts was able to achieve consensus regarding many recommendations for the best care of children with sepsis, acknowledging that most aspects of care had relatively low quality of evidence resulting in the frequent issuance of weak recommendations. Despite this challenge, these recommendations regarding the management of children with septic shock and other sepsis-associated organ dysfunction provide a foundation for consistent care to improve outcomes and inform future research. S14 the group heads, panel members, and methodologists. Searches utilized ...

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confidence: 99%

Surviving sepsis campaign international guidelines for the management of septic shock and sepsis-associated organ dysfunction in children

et al. 2020

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“…Parenteral Ca administration to critically ill patients has been reported to more than double the mortality risk and the risk of acute respiratory failure (12) . These observations are in line with animal studies and may be related to pro-inflammatory actions by Ca (29) .…”

Section: Discussionmentioning

confidence: 99%

“…However, metaanalyses of both interventional and observational studies have failed to demonstrate this association (10,11) . To our knowledge, the relationship between Ca supplements and respiratory mortality has not been investigated in adults, although parenteral Ca administration to critically ill patients has been associated with an increased risk of acute respiratory failure (12) . In line with supplementation, evidence on the association between milk consumption with disease risk and mortality has produced conflicting results.…”

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Association of supplemental calcium and dairy milk intake with all-cause and cause-specific mortality in the UK Biobank: a prospective cohort study

2019

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Excessive Ca intakes have been proposed to associate with vascular calcification and a higher risk of prostate cancer. We investigated the associations of supplemental and dietary Ca intake with mortality using data from 497 828 UK Biobank participants. The average follow-up was 4·2 years and 14 255 participants died, 8297 from cancer, 2959 from CVD and 572 from respiratory disease. The use of Ca supplements and milk consumption were associated with differences in mortality in younger (≤65 years) but not in older participants (>65 years, Pinteraction ≤ 0·04 for all comparisons). Among participants <65 years, there was an inverse association between Ca supplementation (OR 0·91, 95 % CI 0·83, 0·99) and milk consumption (OR 0·93, 95 % CI 0·86, 1·00) with respect to all-cause mortality. In the same age group, milk drinkers had lower odds of cancer mortality (OR 0·89, 95 % CI 0·80, 0·98) but Ca supplement use was associated with increased odds of respiratory mortality (OR 1·69, 95 % CI 1·16, 2·74). All associations in participants aged ≥65 years were null after full adjustment. In sensitivity analyses stratified by hormone replacement therapy, Ca supplement use was associated with decreased odds of cancer mortality in users but increased risk in other women (OR 0·81, 95 % CI 0·69, 0·94 v. OR 1·17, 95 % CI 1·01, 1·35, respectively). To conclude, we saw little evidence for harm with dietary or supplemental Ca. Further studies are required to confirm the proposed interaction with hormone replacement therapy and to exclude reverse causation as a determinant in the association between Ca supplements and increased risk of respiratory diseases.

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“…Therefore, the intersection of the mortality curves was calculated, and we found that patients with calcium supplementation tended to have a higher hospital mortality when their iCa on first ICU admission was approximately 0.94 ~ 1.16 mmol/L, suggesting that attempted blood calcium correction at this interval would be harmful. Because the majority of septic patients' iCa on the first ICU admission was located at this iCa interval, this may explain why some studies revealed that calcium supplementation has an adverse effect on the prognosis of septic patients [16,20] and septic model [21,22]. However, on the contrary, there is a trend showing that calcium supplementation decreased mortality when iCa on the first ICU admission was lower than 0.9 mmol/L and higher than 1.20 mmol/L, although we would not confirm this finding in the survival analysis, probably due to the small number of patients in those subgroups.…”

Section: Calcium Supplementation Had a Double Effect On The Mortalitymentioning

confidence: 99%

“…One large retrospective study showed that calcium supplementation can improve the 28-day and 90-day survival in ICU patients [14]. However, several clinical observation studies have shown that calcium supplementation in critically ill patients provides no benefit or even worsen outcomes [15,16]; moreover, experiments using an animal model of sepsis showed that calcium administration increases mortality [17].…”

Section: Introductionmentioning

confidence: 99%

Calcium supplementation prolongs the time of hospitalization and has a double effect on mortality in septic patients: A retrospective study from MIMIC-III

He¹,

An²,

Huang³

et al. 2020

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Background Hypocalcemia is a common electrolyte disturbance in sepsis, calcium administration in those patients remains a controversial issue. The aim of this study was to assess the association of calcium supplementation with the time of hospitalization and mortality in septic patients. Method 5761 eligible septic patients, including 2689 with calcium supplementation and 3072 without calcium supplementation, were extracted from the MIMIC-III database. A total of 1463 pair patients were included in the analysis after propensity score matching according to the age, sex, SOFA score and lactate on first ICU admission. We compared the length of stay (LOS) in the intensive care unit (ICU) and hospital, as well as the 28-day and hospital mortality, which stratified the analysis according to the Sequential Organ Failure Assessment (SOFA) score, and the iCa on the first ICU admission between the matched groups. Results The results showed that either a too-low or a too-high iCa increased the risk for septic patients, but the minimum of the mortality curve in the non-calcium supplement group was locally in the mild hypocalcemia range. Regardless of the SOFA score and iCa, the LOS in both the ICU and hospital were higher in the calcium supplement group than in the non-calcium supplement group. Overall, the 28-day and hospital mortality were greater but not statistically significant in the calcium supplement group than in the non-calcium supplement group (14.83% vs 13.39%, p=0.416; 16.20% vs 13.88%, p=0.079, respectively). However, the survival analysis stratified by SOFA score showed that calcium supplementation reduced mortality when the patient’s SOFA score was >8 (p=0.028), while it worsen the outcome when the SOFA score was ≤4 (p<0.001) and had no significant effect with SOFA scores from 5~8 (p=0.556). Conclusion Our findings suggest that mild hypocalcemia may be protective in septic patients and that calcium supplementation may prolong hospitalization and have a double effect on mortality. The SOFA score may be a valuable clinical index for calcium administration decision making.

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Calcium Administration Is Associated with Adverse Outcomes in Critically Ill Patients Receiving Parenteral Nutrition: Results from a Natural Experiment Created by a Calcium Gluconate Shortage

Abstract: Calcium administration correlated with adverse outcomes in critically ill patients receiving PN. The data suggest that administration of parenteral calcium to critically ill patients may be harmful.

Cited by 20 publications

References 13 publications

Surviving sepsis campaign international guidelines for the management of septic shock and sepsis-associated organ dysfunction in children

Surviving sepsis campaign international guidelines for the management of septic shock and sepsis-associated organ dysfunction in children

Association of supplemental calcium and dairy milk intake with all-cause and cause-specific mortality in the UK Biobank: a prospective cohort study

Calcium supplementation prolongs the time of hospitalization and has a double effect on mortality in septic patients: A retrospective study from MIMIC-III

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