Intraoperative Hypotension: Marker or Mediator of Disease?

Patrice Wendling

October 25, 2021

Despite the strong association between intraoperative hypotension and postoperative adverse cardiovascular outcomes, a new study suggests universally targeting higher blood pressures during noncardiac surgery may not be the answer.

Previous research suggests the risk of organ injury after noncardiac surgery begins to rise rapidly below a mean arterial blood pressure (MAP) of 65 mm Hg, but there's no universally accepted definition of intraoperative hypotension.

For the present trial, part of the BBB study, Swiss researchers evenly randomly assigned 458 adults over age 45 years at high cardiovascular risk to an intraoperative MAP target of at least 75 mm Hg or at least 60 mm Hg (control), per current 2014 European guidelines for noncardiac surgery.

The primary outcome — a composite of high-sensitivity cardiac troponin I rise on postoperative day 0 to 3 and/or 30-day major adverse cardiovascular events (MACE)/acute kidney injury (AKI) — occurred in 48% of the MAP 75 group and 52% of the control group (P = .42).

As reported online today in the Journal of the American College of Cardiology, there were also no significant reductions in acute myocardial injury (15% MAP 75 group vs 19% control group) or MACE/AKI (45% vs 46%).

One-year MACE, which included new or progressive chronic kidney disease in place of AKI, occurred in 39 patients in the MAP 75 group and 33 patients in the control group.

Notably, the MAP 75 group spent significantly less cumulative time than controls with a MAP less than 65 mm Hg during surgery (median 9 minutes vs 23 minutes).

"Our finding that more than halving strongly prognostically relevant hypotensive time (MAP <65 mm Hg) is not associated with any significant differences in short- or long-term adverse cardiovascular outcomes suggests that simply targeting higher intraoperative BPs in all patients will most likely not lead to meaningful widespread improvements in postoperative outcomes," lead author Patrick M. Wanner, MD, Cantonal Hospital St. Gallen, St. Gallen, Switzerland, and colleagues write.

Speaking to | Medscape Cardiology, Wanner said the results were surprising because of the enormous amount of data indicating that intraoperative hypotension does lead to perioperative organ injury. But, on the other hand, it may have been a "bit too good to be true" to expect one intervention would change 30-day mortality or 30-day MACE, especially when applied to a heterogeneous group of patients. "So, the big question is, which patients need which blood pressure threshold?"

The only previous randomized trial in high-risk noncardiac surgery patients, INPRESS, reported a 27% relative risk reduction in a composite primary outcome of postoperative organ dysfunction using an individualized vs standard blood pressure management strategy.

Asked about the discordant results, Wanner said, "I think we really did just look at different questions." The current study used a generalizable approach to blood pressure management found in many institutions in America and elsewhere and included a large number of vascular surgeries (67%) but also a mix of orthopedic, urologic, and gynecologic operations.

In comparison, he noted that INPRESS looked exclusively at abdominal surgery using a very specific, goal-directed protocol including colloids and blood transfusions and targeted a systolic blood pressure (SBP) within 10% of the patient's normal resting value. Hemodynamic management was also continued for 4 hours postoperatively.

"That's actually an important distinction because, as far as we can tell, many of the complications occur postoperatively. Myocardial injury mostly occurs postoperatively, with more than 90% occurring within 2 days," Daniel I. Sessler, MD, told | Medscape Cardiology. "Because of that I take the postoperative period seriously, and it might be that longer blood pressure management in the INPRESS trial made a difference.

"But the major thing about the current trial is that it's largely based on stage 1 AKI, which isn't even formally acute kidney injury — it's actually risk," said Sessler, chair of Outcomes Research at the Cleveland Clinic, Cleveland, Ohio, and founder of the Outcomes Research Consortium. "About a third of people who develop stage 1 AKI are at least as bad or worse 1 to 2 years later, so that is a meaningful distinction, but AKI doesn't kill directly, at least short term. Myocardial injury can."

Notably, 97% of the study's primary composite outcomes included AKI (two thirds of which were stage 1) and 40% included myocardial injury. In sensitivity analyses that excluded AKI from the composite primary endpoint, both myocardial injury and the primary composite without AKI were more than 20% less common in patients randomly assigned to tight blood pressure control (number needed to treat 25).

"So they're underpowered, but the point estimate was a clinically meaningful 20% reduction," Sessler said. "That's why I say that this trial should not be interpreted as demonstrating that there's no effect. What it tells me is that we need a much larger trial."

In an accompanying editorial, Sessler and Timothy G. Short, MD, University of Auckland, New Zealand, highlight two ongoing randomized trials that should provide "robust information" about the extent to which the association between hypotension and major organ injury is causal, and at what thresholds.

POISE-3 recently completed enrollment and tested various blood pressure management strategies in about 9500 noncardiac surgery patients, whereas GUARDIAN just started but will examine whether tight perioperative blood pressure management reduces serious perfusion-related complications after major noncardiac surgery in some 6200 patients.

Wanner said he hopes their findings spark a discussion about how noncardiac surgery patients are managed intraoperatively and postoperatively.

"The data is mounting that the postoperative phase is certainly important, perhaps even more important than the intraoperative phase because, of course, you will never be better monitored than you are in the operating room," he said. "Whatever happens, we know it's modifiable, in theory, whereas on the wards, it's the Wild West. There's probably a large amount of patients who just go unrecognized who are extremely hypotensive, hypoxemic, anemic. That's something which we'll have to be focusing on more and more in the future."

"And then we get back to this fundamental question of how much of these associations are really markers of comorbidities and how much are really due to the hypotension itself," Wanner said. "When we start looking at the postoperatively phase more conclusively, we may be able to tickle that out."

The study was supported by grants from the Swiss National Science Foundation, the Swiss Heart Foundation, and the Scientific Commission of the Cantonal Hospital St. Gallen, Switzerland. Wanner has received grants from the Swiss Heart Foundation. Sessler has served as a consultant for, and his department has conducted research funded by, Edwards Lifesciences; and has served on advisory boards and has equity interests in Sensifree and Perceptive Medical. Short has served as a consultant for Becton Dickinson and has conducted commercial research for Roche Pharmaceuticals and Boehringer Ingelheim.

J Am Coll Cardiol. Published online October 25, 2021. Full text, Editorial

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