Mr. G is a 59-year-old patient with a history of chronic hypertension who presents to the ICU with septic shock. As his physician, you want to make the best decisions to manage his complicated condition. You recall that the Surviving Sepsis Campaign has guidelines for this very situation, and they recommend reversal of his initial hypotension with vasopressors to a target mean arterial pressure (MAP) of 65 mmHg. However, because Mr. G’s body is accustomed to chronically elevated blood pressures, your intuition tells you that he may benefit from a higher target MAP. After perusing the literature, you find a large retrospective trial that suggests a higher target MAP (>75 mmHg) may help maintain kidney function in patients with chronic hypertension. Furthermore, a small, prospective trial corroborates the benefits of a higher target MAP. Is a higher target MAP the right course for Mr. G? In this week’s issue of NEJM, Asfar et al. attempt to help you answer this question.
In this large, open-label clinical trial, 776 patients with septic shock across 29 centers in France were randomized to resuscitation with either a target MAP of 65-70 mmHg or a higher target of 80-85 mmHg. In addition, patients were stratified according to history of hypertension, because the authors hypothesized that patients with chronic hypertension would benefit more from a higher target MAP. In terms of the primary endpoint—mortality at day 28, there was no difference observed between the 65-70 mmHg and 80-85 mmHg groups. Furthermore, there was no mortality difference observed at 90 days, nor was there any difference in overall rate of serious adverse events between the two groups. There was, however, an increased incidence of de novo atrial fibrillation in the high target MAP group. On the other hand, in the pre-specified stratum of patients with chronic hypertension, the group with the higher target MAP required less renal replacement therapy.
In an accompanying editorial, James A. Russell, MD, points out three main clinical implications of this trial. First, this trial shows that there is no indication for routine use of higher target MAP in septic shock resuscitation given that there was no mortality benefit and that there was an increased incidence of de novo atrial fibrillation in this group. In patients with chronic hypertension, however, he points out that a higher target MAP may be indicated, since it can decrease the use of renal replacement therapy. Finally, after looking at several randomized controlled trials studying vasoactive resuscitation in shock, Russell finds that there are differences in the amounts of fluids vs. vasopressors used for resuscitation across these different trials. He recommends that a more detailed analysis of the proportions of these two treatment modalities, each of which is associated with its own risks, is warranted.
As for Mr. G, your intuition was partly correct. Targeting a higher MAP may help his kidneys, but will he get pulmonary edema if he flips into atrial fibrillation? As with much of medicine, you will have to weigh the benefits against the potential risks. No one ever promised the decision would be easy!