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PostPosted: 08 Jun 2014 01:19 
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Septic Shock: The Case for Different Blood Pressure Targets Andrew F. Shorr, MD, MPH
Associate Professor of Medicine, Department of Pulmonary & Critical Care Medicine, George Washington University; Associate Chief, Department of Pulmonary & Critical Care Medicine, Washington Hospital Center, Washington, DC May 08, 2014

This is Andy Shorr from Washington, DC, with a pulmonary and critical care literature update. I would like to point out an article in the March 18 issue of New England Journal of Medicine that focused on blood pressure targets for patients with septic shock. This article, by Asfar and colleagues,[1] presents a very well-done, multicenter, randomized, open-label study comparing 2 different blood pressure targets for patients with septic shock. Historically, we have targeted a mean arterial pressure (MAP) of 65-70 mm Hg with our fluids and vasopressors. It's unclear whether that number is superior, inferior, or equivalent to a higher target. In certain select conditions, higher blood pressure targets, particularly in neurologic injury, are what we desire and focus on. Perhaps in patients with chronic arterial hypertension, which is a very prevalent disease worldwide and which involves a shift in the relationship between blood pressure and organ perfusion, a higher target may be beneficial. That is what these authors investigated.

In this multicenter trial, they randomly assigned nearly 800 patients to one of 2 blood pressure targets: a MAP of 65-70 mm Hg or a MAP of 80-85 mm Hg. These groups were well balanced. This was a very sick group of patients. The overall mortality rate at the end of the study was approximately 36%, which is what we have seen historically in terms of 28-day mortality in septic shock. Three-fourths of the patients required mechanical ventilation, and the vast majority had lactic acidosis when they presented. Furthermore, unlike other sepsis studies that have recently been published, more than 50% of the patients had pneumonia. So, they studied a very sick cohort of people. It was striking that they saw no difference in 28-day mortality whether the blood pressure target was a MAP of 65-70 mm Hg or 80-85 mm Hg.

How we achieve a target blood pressure is always important because not all vasopressors are equivalent. We know that is true from studies comparing dopamine with norepinephrine in shock. In this study, more than 90% of the patients were receiving norepinephrine. So, there was no interaction according to the medication given to patients to achieve the blood pressure target. In fact, when you look at the data, they did achieve a blood pressure difference in terms of having a goal blood pressure and actually achieving it. You can have a target for blood pressure, but unless you have a well-executed trial, it doesn't mean that you are going to achieve it. Looking at the data presented in the article, clearly the curves for MAP separate between the 2 arms.

Overall, at the end of this trial, mortality was very high and it was not different between the 2 targets. Of interest, requiring a higher target (which, of course, led to a higher dose of norepinephrine) was associated with higher rates of atrial fibrillation; more than a doubling of the rate of atrial fibrillation occurred, from about 2.5% to slightly more than 5%. It is intriguing that when they looked at the subgroup of patients who had chronic hypertension (which was a small subgroup), they saw less superimposed new acute kidney injury in the patients with higher blood pressure targets compared with the patients with lower blood pressure targets. In addition, they saw less need for renal replacement therapy (RRT) in the subgroup of patients with chronic arterial hypertension who had a higher blood pressure target vs those with a lower target. No difference in mortality was seen, but there was a difference in the need for RRT.

The need for RRT was a secondary endpoint, and RRT was not standardized according to the study protocol. RRT is usually cumbersome and expensive. Although the study didn't suggest any differences in the secondary analyses overall, it does suggest that not every patient in the intensive care unit (ICU) needs to be treated in the same fashion. Subgroup analysis is always fraught with issues, and this needs to be considered cautiously. The study authors did some exploratory logistic regression and multivariable analysis in this subpopulation and showed that the interaction between chronic arterial hypertension, higher blood pressure targets, and less need for RRT remained after adjusting for confounders, but this is not a separate study of that population. However, it is intriguing because we believe, physiologically, that patients with chronic atherosclerotic disease and chronic arterial hypertension need a higher blood pressure to perfuse the kidneys, otherwise the kidneys are going to become ischemic and injured and the patient will need RRT. So that fits biologically.

However, I don't think that anyone is advocating having a different blood pressure target for these patients just yet. This study certainly suggests that in the vast majority of patients, a MAP target of 65-70 mm Hg is adequate and that in patients with chronic arterial hypertension, we need more data and further analysis to decide. In the end, it will be similar to learning that a single duration of antibiotic therapy isn't appropriate for every kind of infection or for every kind of patient; it's going to vary according to the site of infection, the kind of pathogen, and so forth. Perhaps we are learning from this that we need to have different blood pressure targets because we have different kinds of patients and they bring different kinds of situations with them to the ICU. This is Andy Shorr from Washington, DC.

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