In this episode I’ll:
1. Discuss an article about the adverse outcomes of calcium administration in critically ill patients.
2. Answer the drug information question “What dose of sulfamethoxazole/trimethoprim should be used to treat stenotrophomonas in a super-morbidly obese patient?”
3. Share a resource I’ve used to convert heparin protocols to anti-Xa monitoring.
Article
Lead author: Bryan Dotson
Published in Pharmacotherapy Early Access October 2016
Background
In episode 73, I discussed a review article in CHEST that argued against the routine replacement of calcium in critically ill patients. The crux of the argument was the lack of benefit for routine calcium replacement. But what if routine calcium replacement is harmful? This would provide a stronger argument for de-adoption of routine calcium replacement. The routine nature of calcium replacement makes it difficult to study interventions that lead to no calcium replacement. However, the IV calcium shortage of 2013 provided an opportunity for researchers to examine differences in outcomes with and without liberal replacement of calcium.
Objectives
The authors sought to determine the association between calcium administration and adverse outcomes in adult critically ill patients receiving parenteral nutrition (PN).
Methods
The study was a retrospective cohort of patients before and during a calcium gluconate shortage in three teaching hospitals. During the period of the shortage, calcium was removed from parenteral nutrition. IV calcium supplementation outside of parenteral nutrition was allowed.
Results
Based on the amount of calcium received, patients were divided into quartiles. The authors measured in-hospital mortality, acute respiratory failure, new-onset shock, and a composite of any one of these endpoints.
For the group of patients not on mechanical ventilation or vasoactive support when PN started, calcium administration was significantly associated with an increase in the odds of mortality, respiratory failure, new-onset shock, and the composite endpoint.
Importantly, the authors found that there was a dose-response relationship; as the dose of calcium increased so did the likelihood of an adverse event.
Conclusion
The authors concluded:
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.
Discussion
Although the study had a limited sample size and was retrospective in nature, the dose-response relationship does provide added weight to the conclusion that calcium replacement correlates with patient harm. Whenever I evaluate a potential therapy for a patient, I consider the following factors:
Efficacy
Safety
Cost
It would appear that routine calcium replacement is ineffective, potentially unsafe, and although it is not expensive it is certainly not free.
Drug information question
Q: What dose of sulfamethoxazole/trimethoprim should be used to treat stenotrophomonas infection in a super-morbidly obese patient?
A: No one knows…
In general, sulfamethoxazole/trimethoprim should be dosed based on actual body weight. The dose of trimethoprim to treat stenotrophomonas is 5mg/kg every 8 hours. In a morbidly obese patient weighing 200 kg, this would result in a massive amount of sulfamethoxazole/trimethoprim – the equivalent of almost 20 Bactrim DS tablets daily! Unfortunately, very limited data is available on the impact of critical illness on the Vd of sulfamethoxazole or trimethoprim. For this reason, a general dose recommendation in morbid obesity cannot be made. Instead, a patient-specific decision on the dose of sulfamethoxazole/trimethoprim must be made, and the response to treatment should be closely monitored.
Resource
ASHP’s Safety and Quality Pearls II is a book that I have recently used to help transition heparin protocols from PTT to anti-Xa. The book provides information on very specific initiatives that other facilities have implemented with a measure of success.
If you like this post, check out my book – A Pharmacist’s Guide to Inpatient Medical Emergencies: How to respond to code blue, rapid response calls, and other medical emergencies.
Hi Joe. I really enjoy your website, thank you for creating such a nice forum to discuss critical care pharmacology. I am a Pulm/CCM physician. I read your summary of the article on calcium replacement and I am a bit confused. Unfortunately, I only have access to the abstract and not the whole article. It appears that this is a retrospective study that tried to make conclusions regarding calcium therapy. Would it be a safe assumption to say that the patients that are on the sicker end of the spectrum tend to be the ones who get calcium replaced? If so, are the quartiles they describe simply a reflection of how ill those patients were and had nothing to do with whether they received calcium or not? Thanks.
Thank you for the kind words and for the great question!
The authors mention that most patient characteristics, including APACHE II score, were similar between the calcium quartiles. They believe that confounding by indication was minimized because the addition of calcium to parenteral nutrition was dictated by the shortage rather than chosen by clinicians.
You had mentioned in episode 73 that you were going to discuss the article by Aberegg at your next critical care meeting. Have you changed your practice with calcium monitoring/replacement based on these two articles? We use an electrolyte replacement protocol at my facility and I am looking into presenting to our intensivists to see about removing it from our standing protocol. Thanks.
Yes, based on that article in CHEST referenced in Episode 73, we removed calcium from our electrolyte replacement protocol.