A guest post by Rory Spiegel (@CaptainBasilEM) who blogs on nihilism and the art of doing nothing at emnerd.com.
Among the many questions in sepsis management, the proper use of vasopressors is one of the most vexing. Despite sparse evidence addressing their overall benefit in the management of septic shock, the use and misuse of vasopressors have been debated ad nauseam. And yet the precise time to begin pressor therapy and the ideal mean arterial pressure (MAP) to target are still very much uncertain.
Authors of the SEPSISPAM trial, or more commonly referred to as “the other sepsis trial published alongside ProCESS“, attempt to provide us with some guidance on the ideal MAP goal in septic shock. Pierre et al randomized 776 patients in septic shock, “refractory” to initial fluid bolus (30mL/kg), initiating vasopressor therapy at a MAP goal of either 65 or 85 mm Hg. The pressor used to achieve these MAPs was left to the discretion of the treating physician (though norepinephrine was the first-line pressor in the vast majority of the participating centers).
SEPSISPAM failed to find a difference between a MAP goal of 65 or 85 mm Hg in any of the many endpoints examined, with the exception of the pre-specified subgroup of patients with a history of hypertension. In those randomized to the 65 mm Hg group, they found a small increase in the amount of patients who experienced elevated creatinine levels and underwent renal replacement therapy within the first week of enrollment. Given that there was no difference in 28-day or 90-day mortality or the number of patients who survived to 28-days without organ support, its hard to imagine this momentary ascent into statistical significance as clinically relevant.
More important than the ideal MAP goal for pressor therapy, is how many of these patients should have been started on vasopressors in the first place? Patients were enrolled after they were found to be refractory to initially fluid bolus and then immediately started on pressors. And though the protocol allowed for physician judgment on additional fluid administration after the initial 30cc/kg bolus, if you examine the daily fluid administration during the first 24-hours of resuscitation, very little extra fluid was allotted. Though these patients received approximately 10 liters over the first 5 days of their resuscitation, only 3 liters were given within the first 24 hours. When compared to the ProCESS cohort, who received approximately 5 liters (depending on group allocation) within the first 6 hours, this resuscitation effort is entirely underwhelming.
It is impossible to make definitive conclusions when comparing outcomes from different trials, but these two cohorts appear fairly similar at the time of enrollment. In fact, the ProCESS cohort may have been slightly sicker (lower MAP, higher HR, higher initial blood lactate levels). These two very similar cohorts with almost identical pre-enrollment fluid administration demonstrated two very different resuscitative strategies. The patients in the SEPSISPAM trial were given very little additional fluid after the initial bolus and were all immediately started on pressor therapy. Conversely, the ProCESS cohort were bolused generous amounts of additional fluid and only half were started on pressors within the first 6-hours of enrollment. The 28-day mortality in the SEPSISPAM cohort was 34% and 36.6% respectively. In contrast, the the ProCESS cohort found a 60-day mortality of 21.0%, 18.2% and 18.9% in the three resuscitative strategies. Obviously not definitive data but a strong argument against the “Fear the Fluids” campaign that is so rampant in current ED and ICU management of septic shock.
“High versus Low Blood-Pressure Target in Patients with Septic Shock” http://www.nejm.org/doi/full/10.1056/NEJMoa1312173