Dose–Response Relationship in Cardiac Surgery:
Ottawa, Ontario, Canada—Cardiac anesthesiologists can add acute kidney injury (AKI) to the many deleterious effects of intraoperative hypotension.
A retrospective cohort study by a team of Canadian investigators found a relationship between kidney injury and mean arterial pressure (MAP) less than 65 mm Hg, but also uncovered evidence of a dose–response relationship with increasing total duration of hypotension.
“We know that acute kidney injury is a common and very serious complication after cardiac surgery, and we also know that renal perfusion is highly dependent on mean arterial pressure,” said Louise Sun, MD, assistant professor of anesthesiology at the University of Ottawa Heart Institute, in Ontario. “Although there are a number of risk models that exist to calculate a patient’s preoperative risk of developing acute kidney injury, none have accounted for the combined effect of hypotension pre-bypass, during and post-bypass.”
Perioperative Hypotension Risk
To shed light on this potential relationship, Dr. Sun and her colleagues at Toronto General Hospital reviewed the records of 2,314 consecutive patients, all of whom underwent major cardiac surgery requiring median sternotomy from November 2009 to July 2014. Acute kidney injury, the primary outcome, was defined by the Acute Kidney Injury Network (AKIN) stage 1 criteria during the first two postoperative days (Table). The trial’s secondary outcome was AKIN stages 2 and 3. Patients were excluded if their preoperative MAP was less than 65 mm Hg, they were dependent on dialysis, or they lacked preoperative or postoperative creatinine measurements.
Primary exposures were the total durations of MAP less than 65 mm Hg before, during and after cardiopulmonary bypass. Blood pressure measurements were recorded every minute in an electronic patient record; artifacts were removed using an automated algorithm. The relationship between intraoperative hypotension and AKI was modeled using multivariate logistic regression, with adjustment for AKI risk factors determined before analysis.
As Dr. Sun reported at the 2015 annual meeting of the Canadian Anesthesiologists’ Society (abstract 84513), AKIN stage 1 occurred in 400 patients (17.3%). Furthermore, every 10 additional minutes of intraoperative hypotension with MAP less than 65 mm Hg during cardiopulmonary bypass was associated with a 6% increase in the odds of AKI (adjusted odds ratio [OR], 1.06; 95% CI, 1.02-1.10). Similarly, every 10 additional minutes of MAP less than 65 mm Hg after bypass were associated with an 11% increased odds of AKI (adjusted OR, 1.11; 95% CI, 1.06-1.16). Prebypass intraoperative hypotension was not associated with kidney injury.
“We also found other important predictors of acute kidney injury,” Dr. Sun said. “Older age was a significant predictor for acute kidney injury, with every 10 years increasing the odds by about 12%. Preexisting hypertension and poor left ventricular ejection fraction were predictors, along with anemia—as defined by the WHO [World Health Organization] definition—and poor renal function as defined by GFR [glomerular filtration rate] less than 60.”
Other predictors included male gender, aortic cross-clamp times longer than 120 minutes, intraoperative transfusion of four units of packed red cells and a need to reopen postoperatively. Of interest, there was no interaction between preoperative hypertension and intraoperative hypotension, or between preoperative anemia and intraoperative transfusion.
AKIN stages 2 and 3 kidney injury occurred in 78 patients (3.4%). Intraoperative hypotension again played a role, as the injury was associated with postbypass hypotension (adjusted OR, 1.18 for every 10 additional minutes of MAP <65 mm Hg; 95% CI, 1.11-1.27) and low-output syndrome.
“In conclusion, there was certainly a dose–response relationship for the duration of hypotension and postoperative acute kidney injury,” she noted. “To our knowledge, this is the first study to address the combined effect of hypotension throughout all periods of cardiac surgery, and certainly provides the impetus for future interventional trials to examine whether a mean arterial pressure or hemodynamic goal-directed therapy would improve outcomes for cardiac surgery.”
Hilary P. Grocott, MD, called the data “compelling.” She said, “It is only through the examination of large data sets such as these that we will be better able to understand the impact hemodynamics may have on renal function.” Dr. Grocott is professor of anesthesia and surgery at the University of Manitoba, in Winnipeg, and editor-in-chief of the Canadian Journal of Anaesthesia.
“Although hypotension defined by this somewhat arbitrary threshold of less than 65 mm Hg is important, it is unlikely that a unifying definition of hypotension such as this will apply to all patients. Perhaps a next step is to understand how to better tailor blood pressure management in individuals. Until that time comes—and I doubt it will be anytime soon—these are important data to help guide clinicians.”