Beta Blockers in Sepsis

General Info/Intro

• In septic shock tachycardia is associated with adverse outcomes. Traditional teaching tells us to treat the root cause of sinus tachycardia, whether it is fever, hypoxia, hypotension, dehydration, pain, or anxiety.
• The use of β-blockers in sepsis seems counterintuitive but some recent studies have shown that in patients with severe sepsis it may be beneficial.
• Beta blockers may have a role in attenuating the deleterious effects of β-adrenergic stimulation in septic shock. Beta blockers may also increase microvascular circulation.
• Beta blockers are not typically used in septic shock because physicians fear their negative inotropic and hypotensive effects in patients with already low blood pressures.

Evidence

• A recent randomized clinical study published in JAMA by Morelli et al in a cohort of 77 septic shock patients showed that “use of esmolol after initial hemodynamic optimization resulted in maintenance of heart rate within the target range of 80/min to 94/min. Compared with standard treatment, esmolol also increased stroke volume, maintained MAP, and reduced norepinephrine requirements without increasing the need of inotropic support or causing adverse effects on organ function. There was an associated improvement in 28-day survival.”
• The primary outcome in the Morelli et al study was heart rate, while the secondary outcomes were hemodynamic and organ function measures; norepinephrine dosages at 24, 48, 72, and 96 hours; and adverse events and mortality occurring within 28 days after randomization. As for any conclusions obtained from any secondary outcomes, the benefit of β-blockers on hemodynamics, organ preservation, norepinephrine requirements, and mortality should be further investigated before it becomes routinely used.
• Whether β-blockers have a role in the emergency department setting is unclear. The study above was done in a cohort of patients in an ICU setting that were already stabilized after 24 hours. Patients were enrolled after 24 hours once they were deemed hemodynamically optimized, which was defined as having a pulmonary artery pressure of ≥ 12 mm Hg and central venous pressures of ≥ 8 mm Hg.
• Another study published by Balik et al showed that the use of esmolol did not result in a significant change in norepinephrine requirements or lactate levels. This study was done in ten septic patients. There was a significant decrease in heart rate and the stroke volume was insignificantly increased. The authors concluded that the use of beta-blockade was cardioprotective in septic shock patients with high cardiac output.
• The importance of the β receptors in septic shock is not entirely new. In the late 1960s, Berk published an article entitled “the treatment of endotoxin shock by beta adrenergic blockade.” This study was done in dogs that were injected with E. coli. The dogs were divided in several groups 1) no treatment 2) fluids, sodium bicarb, calcium, atropine intermittently to maintain hemodynamics AND propranolol 3) same as group 2 but without propranolol.
• The dogs did better with fluids and propranolol, the group 3 dogs needed twice as much fluids as the group 2 dogs but all the dogs were still sacrificed after 72 hours anyways. The post-mortem analysis of group 2 dogs showed less organ damage than the other groups.

Bottom Line/Pearls & Pitfalls

• Excessive adrenergic stimulation in septic patients can result in poor outcomes through direct autonomic dysfunction, myocardial damage, vascular shock, insulin resistance, and increased susceptibility to infection and thrombus formation.
• Tachycardia can be an indicator of excessive adrenergic stress in a septic patient. High plasma catecholamine levels, the use of pressor therapy, and tachycardia are all independently associated with poor outcomes in critically ill patients.
• Beta blockers may improve hemodynamics, organ preservation, pressor requirements, and mortality, but should be further investigated before it becomes routinely used!!
• Although counterintuitive to our traditional approach to treating sinus tachycardia, β-blockers may have a role in septic patients once you have stabilized using your standard approach to sepsis.  Although, it is probably not wise to use β blockers on your crashing sepsis patient who recently arrived to your ED, who would benefit more from generous fluids, antibiotics, airway management, and pressors.

Further Reading