Effect of Heart Rate Control w/ Esmolol on Hemodynamic and Clinical Outcomes in Patients with Septic
The Article: JAMA.2013;310(16):1683-1691.doi:10.1001/jama.2013.278477 Trial registration: clinicaltrials.gov Identifier: NCT01231698
The Idea: To investigate the the effect of using a short acting beta blocker (esmolol) in patients who are in severe septic shock (article was published prior to the new Sepsis III criteria). To see if using esmolol to decrease HR was more beneficial in comparison to fluid resuscitation in severe sepsis.
The Study: Open-labeled, randomized phase 2 study, conducted in an 18 bed-ICU at the University of Rome Hospital. Patients were enrolled November 2010-July 2012. Inclusion criteria: In severe septic shock requiring norepinephrine to maintain a MAP>65, HR >95 and no prior hx/use of beta blockers prior to being admitted. Patients were properly resuscitated with IVF for 24hours and if the patients still required norepi to maintain MAP>65, they were enrolled in the study. There were a total of 154 patients enrolled, randomized into esmolol vs fluid resuscitation groups. The study then became unblinded 2/2 having to titrate the esmolol drips. The esmolol drip was used to keep the patients HR between 80-94 beats per minuted. Patients in both groups were monitored for a total of 96 hours. The following values were noted: Norepi dosage/needs, stroke volume index, LV stroke volume, lactatemia, fluid requirements, kidney/liver function and mortality.
The Results: Within the 96 hours of monitoring, the group on esmolol did statistically better. Despite being on an esmolol drip, the MAP was maintained despite requiring lower dosages of norepi. SV, SVR and LV stroke volume indices were increased. Arterial lactate values were decreased. Kidney function was better maintained. There was no statistical difference in liver function in the esmolol group vs control group. There was a decrease in myocardial injury (based off infarction markers). Mortality was 49.4% vs 80.5% in the control group. Despite these results, the primary outcome in the investigation was reducing the HR below the predefined threshold of 95/min to keep it between 80-94/min. (It is unclear how this investigation came to the conclusion of this HR).
The Take Away: Sepsis often induces a sympathetic over-stimulation. With that over-stimulation, tachycardia is induced which can lead to increased oxygen demand not only to the heart but to the rest of the body tissues/organs. Is it a good idea to interfere with the body’s natural response to infection? Hypovolemia? Flight or fight response? I would like to think yes, the use of esmolol clearly demonstrated promising results but this study was limited due to its small patient sample/size and it was carried out in an ICU setting instead of an ER setting. This is a very interesting concept I hope to see more research about in the future.