Kencee K. Graves, MD

Clinical question: Does hydrocortisone therapy prevent progression to septic shock in patients with severe sepsis without shock?

Background: Current sepsis management guidelines recommend use of hydrocortisone in patients with septic shock who are unable to restore hemodynamic stability with IV fluids and pressors; current guidelines also recommend against use of corticosteroids without shock. However, these recommendations are based on two RCTs and remain controversial.

Study design: Multicenter, placebo-controlled, double-blind RCT.

Setting: Thirty-four intermediate or intensive care units in German university and community hospitals.

Synopsis: Investigators randomly assigned 380 patients to hydrocortisone or placebo. Patients were included if they had clinical evidence of infection, evidence of SIRS (systemic inflammatory response syndrome), and evidence of organ dysfunction. Patients were excluded if they had any of the following: sepsis-induced hypotension, separate indication for systemic steroid use, or hypersensitivity to steroids. Primary outcome was the occurrence of septic shock within 14 days. Secondary outcomes included time to septic shock or death, death in the ICU or hospital, organ dysfunction, ventilator therapy, renal replacement therapy, and secondary infection.

Study results showed no significant difference in the primary outcome between groups, or in any of the secondary outcomes. In a post-hoc analysis, there was more hyperglycemia and less delirium in the study group.

Study limitations are inclusion of patients only after consent, potentially missing early septic shock, and the fact that many analyses were done post-hoc.

Bottom line: Steroids should be avoided in severe sepsis without shock.

Citation: Keh D, Trips E, Marx G, et al. Effect of hydrocortisone on development of shock among patients with severe sepsis. JAMA. 2016;316(17):1775-85.
 

Dr. Graves is an assistant professor at the University of Utah School of Medicine and associate program director of quality and patient safety for the University of Utah Internal Medicine residency training program.

Clinical question: Does hydrocortisone therapy prevent progression to septic shock in patients with severe sepsis without shock?

Background: Current sepsis management guidelines recommend use of hydrocortisone in patients with septic shock who are unable to restore hemodynamic stability with IV fluids and pressors; current guidelines also recommend against use of corticosteroids without shock. However, these recommendations are based on two RCTs and remain controversial.

Study design: Multicenter, placebo-controlled, double-blind RCT.

Setting: Thirty-four intermediate or intensive care units in German university and community hospitals.

Synopsis: Investigators randomly assigned 380 patients to hydrocortisone or placebo. Patients were included if they had clinical evidence of infection, evidence of SIRS (systemic inflammatory response syndrome), and evidence of organ dysfunction. Patients were excluded if they had any of the following: sepsis-induced hypotension, separate indication for systemic steroid use, or hypersensitivity to steroids. Primary outcome was the occurrence of septic shock within 14 days. Secondary outcomes included time to septic shock or death, death in the ICU or hospital, organ dysfunction, ventilator therapy, renal replacement therapy, and secondary infection.

Study results showed no significant difference in the primary outcome between groups, or in any of the secondary outcomes. In a post-hoc analysis, there was more hyperglycemia and less delirium in the study group.

Study limitations are inclusion of patients only after consent, potentially missing early septic shock, and the fact that many analyses were done post-hoc.

Bottom line: Steroids should be avoided in severe sepsis without shock.

Citation: Keh D, Trips E, Marx G, et al. Effect of hydrocortisone on development of shock among patients with severe sepsis. JAMA. 2016;316(17):1775-85.
 

Dr. Graves is an assistant professor at the University of Utah School of Medicine and associate program director of quality and patient safety for the University of Utah Internal Medicine residency training program.

Clinical question: Does hydrocortisone therapy prevent progression to septic shock in patients with severe sepsis without shock?

Background: Current sepsis management guidelines recommend use of hydrocortisone in patients with septic shock who are unable to restore hemodynamic stability with IV fluids and pressors; current guidelines also recommend against use of corticosteroids without shock. However, these recommendations are based on two RCTs and remain controversial.

Study design: Multicenter, placebo-controlled, double-blind RCT.

Setting: Thirty-four intermediate or intensive care units in German university and community hospitals.

Synopsis: Investigators randomly assigned 380 patients to hydrocortisone or placebo. Patients were included if they had clinical evidence of infection, evidence of SIRS (systemic inflammatory response syndrome), and evidence of organ dysfunction. Patients were excluded if they had any of the following: sepsis-induced hypotension, separate indication for systemic steroid use, or hypersensitivity to steroids. Primary outcome was the occurrence of septic shock within 14 days. Secondary outcomes included time to septic shock or death, death in the ICU or hospital, organ dysfunction, ventilator therapy, renal replacement therapy, and secondary infection.

Study results showed no significant difference in the primary outcome between groups, or in any of the secondary outcomes. In a post-hoc analysis, there was more hyperglycemia and less delirium in the study group.

Study limitations are inclusion of patients only after consent, potentially missing early septic shock, and the fact that many analyses were done post-hoc.

Bottom line: Steroids should be avoided in severe sepsis without shock.

Citation: Keh D, Trips E, Marx G, et al. Effect of hydrocortisone on development of shock among patients with severe sepsis. JAMA. 2016;316(17):1775-85.
 

Dr. Graves is an assistant professor at the University of Utah School of Medicine and associate program director of quality and patient safety for the University of Utah Internal Medicine residency training program.

Clinical question: Does dabigatran or rivaroxaban have more bleeding episodes?

Background: Alternatives to warfarin exist for stroke prevention in nonvalvular atrial fibrillation (AF). The RE-LY and ROCKET-AF trials demonstrated noninferiority to warfarin for both dabigatran (a direct thrombin inhibitor) and rivaroxaban (a factor Xa inhibitor), respectively. Although indirect comparisons have been done using data from these trials, direct, head-to-head comparisons are not available.

Study design: New-user cohort study.

Setting: Medicare beneficiaries 65 years or older with AF and a prescription for either dabigatran or rivaroxaban.

Intracranial hemorrhage and extracranial major bleeding events were significantly greater in the rivaroxaban group than the dabigatran group. There was no significant difference in thromboembolic stroke events.

Limitations include short treatment and follow-up times. Additionally, the study is not generalizable to younger populations.

Bottom line: In elderly patients with non-valvular AF, rivaroxaban was associated with more adverse bleeding events than dabigatran, with no difference in stroke prevention.

Citation: Graham DJ, Reichman ME, Wernecke M, et al. Stroke, bleeding, and mortality risks in elderly Medicare beneficiaries treated with dabigatran or rivaroxaban for nonvalvular atrial fibrillation. JAMA Intern Med. 2016;176:1662-71.

Dr. Graves is an assistant professor at the University of Utah School of Medicine and associate program director of quality and patient safety for the University of Utah Internal Medicine residency training program.

Clinical question: Does dabigatran or rivaroxaban have more bleeding episodes?

Background: Alternatives to warfarin exist for stroke prevention in nonvalvular atrial fibrillation (AF). The RE-LY and ROCKET-AF trials demonstrated noninferiority to warfarin for both dabigatran (a direct thrombin inhibitor) and rivaroxaban (a factor Xa inhibitor), respectively. Although indirect comparisons have been done using data from these trials, direct, head-to-head comparisons are not available.

Study design: New-user cohort study.

Setting: Medicare beneficiaries 65 years or older with AF and a prescription for either dabigatran or rivaroxaban.

Intracranial hemorrhage and extracranial major bleeding events were significantly greater in the rivaroxaban group than the dabigatran group. There was no significant difference in thromboembolic stroke events.

Limitations include short treatment and follow-up times. Additionally, the study is not generalizable to younger populations.

Bottom line: In elderly patients with non-valvular AF, rivaroxaban was associated with more adverse bleeding events than dabigatran, with no difference in stroke prevention.

Citation: Graham DJ, Reichman ME, Wernecke M, et al. Stroke, bleeding, and mortality risks in elderly Medicare beneficiaries treated with dabigatran or rivaroxaban for nonvalvular atrial fibrillation. JAMA Intern Med. 2016;176:1662-71.

Dr. Graves is an assistant professor at the University of Utah School of Medicine and associate program director of quality and patient safety for the University of Utah Internal Medicine residency training program.

Clinical question: Does dabigatran or rivaroxaban have more bleeding episodes?

Background: Alternatives to warfarin exist for stroke prevention in nonvalvular atrial fibrillation (AF). The RE-LY and ROCKET-AF trials demonstrated noninferiority to warfarin for both dabigatran (a direct thrombin inhibitor) and rivaroxaban (a factor Xa inhibitor), respectively. Although indirect comparisons have been done using data from these trials, direct, head-to-head comparisons are not available.

Study design: New-user cohort study.

Setting: Medicare beneficiaries 65 years or older with AF and a prescription for either dabigatran or rivaroxaban.

Intracranial hemorrhage and extracranial major bleeding events were significantly greater in the rivaroxaban group than the dabigatran group. There was no significant difference in thromboembolic stroke events.

Limitations include short treatment and follow-up times. Additionally, the study is not generalizable to younger populations.

Bottom line: In elderly patients with non-valvular AF, rivaroxaban was associated with more adverse bleeding events than dabigatran, with no difference in stroke prevention.

Citation: Graham DJ, Reichman ME, Wernecke M, et al. Stroke, bleeding, and mortality risks in elderly Medicare beneficiaries treated with dabigatran or rivaroxaban for nonvalvular atrial fibrillation. JAMA Intern Med. 2016;176:1662-71.

Dr. Graves is an assistant professor at the University of Utah School of Medicine and associate program director of quality and patient safety for the University of Utah Internal Medicine residency training program.