Tight BP Management Prevents Organ Dysfunction

In what might be the first study of its kind, a team of French researchers has found that an individualized tight approach to blood pressure management reduces the risk for postoperative organ dysfunction compared with standard hemodynamic management. These results, they noted, have far-reaching implications given how common hemodynamic instability and arterial hypotension are during general anesthesia and surgery, and the ease with which the individualized approach can be applied.

“Over the last few years, there has been a large body of compelling evidence that intraoperative care influences postoperative outcomes, especially in sicker patients,” said Emmanuel Futier, MD, PhD, professor of anesthesiology and critical care medicine at University Hospital of Clermont-Ferrand, in Clermont-Ferrand, France. “Specifically, a significant amount of data have been collected on the relationship between intraoperative fluid management and postoperative outcome, and now there is a strong rationale supporting the individualization of fluid administration based on objective hemodynamic goals during surgery in high-risk patients.”

As Dr. Futier described, intraoperative arterial hypotension is common during surgical general anesthesia, and there is a strong association between hypotension and postoperative organ dysfunction and increased postoperative mortality. Nevertheless, there has not been clear, high-level evidence that treating arterial hypotension improves outcome.

Although several current guidelines—including those from the American College of Cardiology and the American Heart Association—recommend individualized care for surgical patients with associated comorbidities, randomized trials using an individualized approach to arterial blood pressure management in surgical patients are sparse.

To fill this gap, Dr. Futier and his colleagues enrolled 298 adult patients into their trial. All of the participants were at increased risk for postoperative complications due to a preoperative acute kidney injury risk index of class III or higher, indicating a moderate to high risk for postoperative kidney injury. Each patient underwent major surgery under general anesthesia. Patients were enrolled from Dec. 4, 2012 through Aug. 28, 2016, as part of the INPRESS (Intraoperative Norepinephrine to Control Arterial Pressure) study—a multicenter, randomized, parallel-group trial conducted in nine French hospitals.

The trial’s individualized management strategy used a continuous infusion of norepinephrine (10 mcg/mL) to achieve systolic blood pressure (SBP) within 10% of the reference value, which was the patient’s resting SBP. By comparison, the standard management strategy calls for treating SBP that is either less than 80 mm Hg or lower than 40% of the patient’s reference value using intravenous ephedrine administered in 6-mg boluses. In all cases, blood pressure was managed throughout surgery and for another four hours postoperatively. “Anesthesiologists should also remember that the definition of usual patient’s blood pressure does not refer to arterial pressure just before induction of anesthesia,” Dr. Futier pointed out.

Benefits of Individualized Care

The study’s primary outcome was a composite of systemic inflammatory response syndrome and dysfunction of at least one organ system (renal, respiratory, cardiovascular, coagulation and neurologic) by postoperative day 7. Secondary outcomes included durations of ICU and hospital stay, adverse events and 30-day all-cause mortality.

As reported in a recent issue of the Journal of the American Medical Association (JAMA 2017 Sep 27. PMID: 28973220), 292 patients completed the trial (mean age, 70±7 years; 15.1% women) and were included in the modified intention-to-treat analysis. It was found that the primary outcome event occurred in 56 of 147 patients (38.1%) who received individualized treatment, compared with 75 of 145 of those (51.7%) assigned to the standard management strategy (relative risk, 0.73; 95% CI, 0.56-0.94; P=0.02). Furthermore, whereas 68 patients (46.3%) in the individualized treatment group experienced postoperative organ dysfunction by day 30, the adverse event occurred in 92 of their counterparts (63.4%) in the standard management group (adjusted hazard ratio, 0.66; 95% CI, 0.52-0.84; P=0.001).

There were no other significant differences between the groups in severe adverse events or 30-day mortality. “It’s especially important to note that there were no statistically nor clinically relevant differences in intraoperative blood losses, which is a common fear of surgeons when higher blood pressure levels are applied,” Dr. Futier said.

As Dr. Futier told Anesthesiology News, the findings have significant potential to affect clinical practice. “This study is, to the best of our knowledge, the first to demonstrate that a strategy aimed at individualizing arterial blood pressure targets—tailored to the patient’s usual blood pressure—can reduce postoperative organ dysfunction. These findings have clear implications in routine practice, given the high frequency of hemodynamic instability and arterial hypotension during general anesthesia and surgery.

“Furthermore,” he said, “the strategy is very easy to apply and doesn’t require [a] big expenditure for an expensive treatment. You just need to know the usual blood pressure of the patient. This is obviously the case for every patient scheduled to elective surgery, but clearly much more difficult for emergency surgery and/or in ICU patients.”

Despite the strength of the findings, Dr. Futier was quick to note that they may not be applicable to all subsets of patients. “It should be kept in mind that we selected a population of patients at high risk of morbidity. It cannot be ruled out that our results might have been somewhat different if the strategy had been applied to lower-risk patients.” The researchers stressed that the study should be replicated in other patient populations before the individualized strategy can be recommended for widespread use.

Daniel I. Sessler, MD, the Michael Cudahy Professor and chair of outcomes research at the Cleveland Clinic, in Ohio, was impressed with the research. “This is exactly the study we needed,” he said. “We and others have shown that there is a strong association between hypotension and myocardial injury, acute kidney injury and death. Risk starts to increase when intraoperative mean arterial pressure reaches 65 mm Hg, and increases exponentially at lower pressures. However, it was unclear whether hypotension was simply a marker for high-risk patients or whether hypotension is causally related to major complications. [Dr.] Futier’s results indicate that the relationship is causal.”

Yet, as with any study, the current trial is not without its shortcomings, as Dr. Sessler pointed out. He noted that the intervention level in the routine-care group was an SBP of 80 mm Hg, “which is fairly low. Many clinicians would normally intervene well before blood pressure reaches that level.” Other limitations noted by Dr. Sessler included:

• The investigators did not report the amounts of time patients spent below various hypotensive thresholds, such as a mean arterial pressure of less than 65 mm Hg. As such, it is unknown how much exposure patients in each group had to critically low pressures.
• Differences in the primary outcome were almost entirely due to acute renal injury and altered consciousness. Renal injury is understandable, but altered consciousness is curious since the brain is probably relatively protected against hypotension.
• There was only one myocardial infarction detected in nearly 300 high-risk patients. Many more would have been expected.

Dr. Sessler pointed out that “these are simply considerations to guide interpretation and future studies … which are clearly needed. They do not detract from the importance of [Dr.] Futier’s trial and the critical causal link he and his colleagues have established between intraoperative hypotension and major complications.”