In this episode I’ll:
1. Discuss an article analyzing higher versus lower blood pressure targets for vasopressor therapy septic and vasodilatory shock.
2. Answer the drug information question “Should a higher dose of heparin be used for VTE prophylaxis in obese patients?”
3. Share a resource for patient education materials on sepsis.
Lead author: François Lamontagne
Published in Intensive Care Medicine December 2017
Until the 2016 update of the Surviving Sepsis Guidelines, patients in shock who had underlying chronic hypertension were thought to benefit from higher MAP targets. The authors of this study conducted an individual patient-data meta-analysis of recent trials to determine if chronic hypertension or other patient variables modify the effect of different MAP targets.
The authors looked at randomized controlled trials of higher versus lower blood pressure targets for vasopressor therapy in adult patients in shock. A modified version of the Cochrane Collaboration’s instrument was used to assess the risk of bias of included trials. The primary outcome of this study was 28-day mortality.
A total of 894 patients across the trials that met inclusion criteria were analyzed. The odds ratio for 28-day mortality for the higher versus lower MAP targets was 1.15 (95% confidence interval 0.87–1.52). The risk of death increased in higher MAP groups among patients on vasopressors > 6 hours before randomization (odds ratio 3.00, 95% confidence interval 1.33–6.74).
The authors concluded:
Targeting higher blood pressure targets may increase mortality in patients who have been treated with vasopressors for more than 6 h. Lower blood pressure targets were not associated with patient-important adverse events in any subgroup, including chronically hypertensive patients.
The 2016 Surviving Sepsis Guidelines now give a strong recommendation favoring an initial MAP target of 65 mm Hg over higher MAP targets. The guidelines go on to state:
When a better understanding of any patient’s condition is obtained, this target should be individualized to the pertaining circumstances.
With this meta-analysis, it seems clear that a history of chronic hypertension is no longer sufficient to recommend a higher MAP target.
Drug information question
Q: Should a higher dose of unfractionated heparin be used for VTE prophylaxis in obese patients?
A: Increasing the dose beyond 5000 units subcutaneously every 8 hours may increase the risk of bleeding without preventing more VTE.
The optimal dose of unfractionated heparin for prophylaxis in obese patients is unknown. In August 2016 a single-center retrospective observational cohort study attempted to answer the question. 1335 patients weighing more than 100 kg on admission received either subcutaneous UFH 7500 units every 8 hours (high-dose group) or 5000 units every 8 hours (low-dose group) for VTE prophylaxis.
The incidence of VTE was similar between groups. When the patients were stratified according to obesity class, the incidence of VTE was still similar between the high and low dose groups. Bleeding complications, however, were significantly higher for patients in the high-dose UFH group. The proportion of patients with a 2 g/dL or greater hemoglobin drop from admission was higher in patients in the high-dose groups in obese classes II and III (30% vs. 18% p<0.01). Furthermore, the proportion of patients who received at least 2 units of packed red blood cell transfusion were significantly higher in patients in the high-dose group who were in obese class III (11% vs 5% p<0.01).
Recommendations for higher VTE prophylaxis dosing should remain on a case-by-case basis, where the evidence points to greater efficacy with acceptable risks, such as in bariatric surgery patients.
The resource for this episode is the Sepsis Alliance. Sepsis Alliance is the largest sepsis advocacy organization in the U.S. working in all 50 states to save lives and reduce suffering from sepsis. Sepsis Alliance is a charitable organization run by a dedicated team who share a strong commitment to battling sepsis. The Sepsis Alliance has many resources for patients, family members, and for medical professionals. The resources include posters, infographics, videos, and information guides.
Vasopressor choice in sepsis
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.