Jim Kling

May 20, 2015

DENVER — In elderly patients with distributive shock in critical care, a higher target for mean arterial pressure leads to an increase in mortality, a pilot study warns.

"Despite the common use of vasopressors, we don't really have any evidence to guide us on the right dose" or the right target, said Andrew Seely, MD, from the University of Ottawa in Ontario, Canada.

"There are arguments for why there might be benefit and harm from higher doses," he told Medscape Medical News here at the American Thoracic Society 2015 International Conference.

The results are an interesting contrast to those from the SEPSISPAM study, which was widely hailed as an important step, said session moderator Greg Martin, MD, from Emory University in Atlanta.

SEPSISPAM showed that in patients with septic shock and chronic hypertension, higher blood pressure targets reduced the incidence of the doubling of blood creatinine levels and reduced the rate of renal-replacement therapy (N Engl J Med. 2014;370:1583-1593).

The current study, however, showed no benefit in this patient population.

SEPSISPAM "was the hallmark of a new area that needs to be thought more about," Dr. Martin told Medscape Medical News.

Vasopressor therapy "is something we do every day, but we don't have good evidence for targets, nor do we even have a good sense of what the variability of clinical practice is," he explained.

In their randomized controlled trial, Dr Seely and his colleagues assessed fluid-resuscitated, critically ill hypotensive adults treated at 10 centers in Canada and one in the United States. Fifty-eight patients were randomized to the higher target of 75 to 80 mm Hg and 60 were randomized to the lower target of 60 to 65 mm Hg.

The baseline characteristics of patients in the two groups were similar, except there were fewer cases of chronic hypertension in the higher-target group than in the lower-target group (33% vs 57%).

There was a significant difference in pressure between the higher-target and lower-target groups (79 vs 70 mm Hg; P < .001).

Table. Outcomes in the Study Cohort

Outcome Higher Target Lower Target P Value
Duration of vasopressor therapy, days 6.5 4.9 .007
Dose of vasopressor therapy, mg 19 13 .046
Urine output, L/day 1.7 1.2 .03
6-month mortality, % 41.0 37.0 .71
Death or persistent organ dysfunction at 28 days, % 3.0 42.0 1.00


Fluid balance and fluid intake were similar in the two groups.

There were more cardiac arrhythmias in the higher-target group than in the lower-target group, but the difference was not significant (36% vs 20%; P = .07). There were no other differences in adverse events between the two groups.

However, in the higher-target group, there was an increased risk for hospital mortality in patients 75 years and older than in patients 16 to 74 years of age (odds ratio, 9.8 vs 0.7; P = .01).

The mortality risk in the older population is the most important finding of the study, said Dr. Seely.

Our team has proven that an analysis of critically ill patients — a population difficult to recruit for clinical trials — is possible, he added.

We need to do a larger study that proves or disproves the hypothesis that the liberal use of vasopressors is killing elderly patients.

"We need to do a larger study that proves or disproves the hypothesis that the liberal use of vasopressors is killing elderly patients," Dr. Seely acknowledged. He reported that his group is applying for funding for such a trial.

In the meantime, Dr. Seely suggested that patients be kept at a pressure close to 65 mm Hg. He pointed out that in the lower-target group, pressure was 70 mm Hg, which suggests that healthcare workers are erring away from hypotension.

"Don't err above the target; aim for the target," he advised. "I think we should do that until we have more evidence to give us better guidance."

The fact that this study showed no benefit of a higher target in hypertensive patients is a surprise, given the SEPSISPAM finding. "In this study, it seemed to be more age-dependent. That needs to be reconciled," said Dr. Martin. "You would think that they would overlap, because older people are more likely to have chronic hypertension. It may be that the two studies showed two different perspectives on the same problem."

Dr. Seely and Dr. Martin have disclosed no relevant financial relationships.

American Thoracic Society (ATS) 2015 International Conference: Abstract A6418. Presented May 19, 2015.


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