Study Finds No Benefit of Parenteral Calcium for ICU Patients with Hypocalcemia, Raises Concerns Over Potential Harm

"Intravenous calcium administration showed no significant impact on 180-day mortality (aHR: 1.18) or time to shock resolution (aOR: 0.81). Moreover, in patients with sepsis and mild hypocalcemia, calcium treatment was associated with increased 90-day (aHR: 1.88) and 180-day (aHR: 1.79) mortality risks," the researchers reported in the Journal of Intensive Medicine.

Hypocalcemia is a frequent condition among ICU patients. Still, the use of calcium therapy in critically ill individuals remains controversial due to conflicting outcome data and a lack of detailed subgroup analyses. To address this gap, Max Melchers, Department of Intensive Care Medicine, Gelderse Vallei Hospital, The Netherlands, and colleagues aimed to explore the relationship between parenteral calcium administration and clinical outcomes in critically ill patients with hypocalcemia, both with and without sepsis.

For this purpose, the researchers conducted a retrospective cohort study involving patients who developed hypocalcemia within the first seven days of admission to a mixed medical-surgical adult ICU at a university-affiliated teaching hospital. The study included patients admitted for at least 48 hours between October 1, 2015, and September 1, 2020, who were not receiving renal replacement therapy.

Primary outcomes assessed were all-cause 180-day mortality and time to shock resolution. Subgroup analyses were performed for patients with sepsis and non-sepsis, categorized by mild or moderate hypocalcemia based on median splits. Proportional hazard regression analyses were utilized to examine the relationship between parenteral calcium administration and clinical outcomes.

The following were the key findings of the study:

Study Population:

• Out of 1100 included patients:
  • 427 (38.8%) were admitted for sepsis.
  • 576 (52.4%) received parenteral calcium.

Primary Findings:

1. Overall 180-Day Mortality:
   • There were no significant difference between patients who received and did not receive parenteral calcium (aHR: 1.18).
2. Time to Shock Resolution:
   • Intravenous calcium reduced the probability of a shorter time to shock resolution (adjusted odds ratio: 0.81).

Subgroup Analyses:

1. Sepsis vs. Non-Sepsis Patients:
   • There were no significant association between calcium administration and 180-day mortality in patients with sepsis (aHR: 1.63) or without sepsis (aHR: 1.06).
2. Sepsis and Mild Hypocalcemia:
   • Parenteral calcium was associated with increased risks of:
     • 90-day mortality (aHR: 1.88).
     • 180-day mortality (aHR: 1.79).

The study showed that hypocalcemia and subsequent parenteral calcium administration (PCA) were prevalent in this large cohort of critically ill patients. However, PCA did not improve clinical outcomes; instead, it was linked to delayed shock resolution and reduced long-term survival in patients with sepsis.

"These findings highlight the importance of exercising caution when administering calcium routinely to critically ill patients with hypocalcemia. A randomized controlled trial (RCT) is needed to validate these results, investigate the underlying mechanisms, and develop evidence-based treatment guidelines," the researchers concluded.

Reference:

Melchers, M., Moonen, H. P. F. X., Breeman, T. M., Van Bree, S. H. W., & Van Zanten, A. R. H. (2024). Parenteral calcium administration and outcomes in critically ill patients with hypocalcemia: A retrospective cohort study. Journal of Intensive Medicine. https://doi.org/10.1016/j.jointm.2024.08.003