In this episode I’ll:
1. Discuss an article about levosimendan in sepsis.
2. Answer the drug information question “Should catecholamines be started before intubating a patient with severe pulmonary hypertension?”
3. Share a resource about how to become a peer-reviewer for a medical journal.
The Critical Care Pharmacy Academy Beta Program is entering it’s 3rd month. I look forward to opening the Academy up to everyone in December 2016! To sign up to be notified immediately when the Academy opens go to pharmacyjoe.com/academy.
Article
Levosimendan for the Prevention of Acute Organ Dysfunction in Sepsis
Lead author: Anthony C. Gordon
Published in New England Journal of Medicine October 2016
Background
Levosimendan is a calcium sensitizer used internationally for acute decompensated heart failure. It enhances myocardial contractility (without increasing oxygen requirements), and causes coronary and systemic vasodilation. In a small 2015 meta-analysis, Levosimendan demonstrated reduced mortality in septic shock patients when compared to dobutamine. The authors of this study sought to determine whether the addition of levosimendan to standard care affected outcomes in patients with sepsis.
Methods
In this double-blind, randomized, placebo-controlled trial patients received placebo or levosimendan (at a dose of 0.05 – 0.2 μg / kg /min) for 24 hours. The primary outcome was the mean daily Sequential Organ Failure Assessment (SOFA) score in the intensive care unit up to day 28. Secondary outcomes were 28-day mortality, time to weaning from mechanical ventilation, and adverse events.
Results
516 patients were enrolled and divided into the placebo and levosimendan groups. There was no significant difference in mean SOFA score between the levosimendan and placebo groups. Likewise, mortality at 28 days did not differ between groups. In the subset of patients that required mechanical ventilation at baseline, those in the levosimendan group were significantly less likely vs. placebo to be successfully weaned from mechanical ventilation over the period of 28 days (hazard ratio, 0.77). The absolute incidence of supraventricular tachyarrhythmia was 2.7% higher in the levosimendan group. This resulted in a number needed to harm of 37.
Conclusion
The authors concluded:
The addition of levosimendan to standard treatment in adults with sepsis was not associated with less severe organ dysfunction or lower mortality. Levosimendan was associated with a lower likelihood of successful weaning from mechanical ventilation and a higher risk of supraventricular tachyarrhythmia.
Discussion
In this study, levosimendan was started on average 15 hours after sepsis was diagnosed. I’m not clear why it was employed vs placebo in patients with sepsis rather than compared to dobutamine in a subset of septic shock patients likely to benefit. Although this was not a positive study, there is still the possibility that a subset of septic patients might still be proven to benefit from levosimendan therapy.
Drug information question
Q: Should catecholamines be started before intubating a patient with severe pulmonary hypertension?
A: Yes!
Intubating a patient with severe pulmonary hypertension carries a high risk of losing right ventricular contraction and cardiovascular collapse. For this reason, every attempt should be made to avoid intubation. A sedative with minimal effect on cardiac function such as etomidate should be chosen, and catecholamines such as dobutamine or norepinephrine should be started in advance of intubation.
Resource
The Wiley Online Library lists different ways that you can become a reviewer for a peer-reviewed journal. They advise:
There is no one way to become a reviewer, but there are some common routes. These include:
• Asking a colleague who already reviews for a journal to recommend you
• Networking with editors at professional conferences
• Becoming a member of a learned society and then networking with other members in your area
• Contacting journals directly to inquire if they are seeking new reviewers
• Seeking mentorship from senior colleagues
• Working for senior researchers who may then delegate peer review duties to you
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.
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