TRICS III: Restrictive blood transfusion strategy safe for cardiac surgery

ANAHEIM, Calif. — A restrictive strategy for red blood cell transfusion was noninferior to a more liberal strategy for mortality and major morbidity in patients undergoing cardiac surgery with cardiopulmonary bypass, according to data from the TRICS III trial.

Perspective from Michael Tong, MD, MBA

The randomized, multicenter, open-label, noninferiority trial included 5,243 patients undergoing cardiac surgery with cardiopulmonary bypass who had moderate to high risk for mortality (EuroSCORE I 6). All patients were randomly assigned to a restrictive red-cell transfusion strategy if hemoglobin was < 7.5 g/dL in the intraoperative or postoperative period or to a liberal strategy if hemoglobin was < 9.5 g/dL in the intraoperative or postoperative period in the ICU, or < 8.5 g/dL in the non-ICU ward.

The primary outcome — a composite of all-cause mortality, nonfatal MI, stroke or new-onset renal failure with dialysis from index hospitalization to discharge or 28 days after surgery — occurred in 11.4% of the restrictive-transfusion group vs. 12.5% of the liberal-transfusion group (95% CI, –2.93 to 0.72; OR = 0.9; 95% CI, 0.76-1.07).

When the researchers examined mortality only, the rate was 3% in the restrictive-transfusion group vs. 3.6% in the liberal-transfusion group (OR = 0.85; 95% CI, 0.62-1.16).

Overall, 52.3% of patients received a red cell transfusion in the restrictive-transfusion group vs. 72.6% in the liberal-transfusion group (OR = 0.41; 95% CI, 0.37-0.47).

Results showed no significant differences between the two strategies in secondary outcomes including ICU and hospital lengths of stay, duration of mechanical ventilation, prolonged state of low cardiac output, infections, acute kidney injury, seizure delirium and encephalopathy.

The data were simultaneously published in The New England Journal of Medicine.

Avoidance of unnecessary blood transfusions is a high priority, and determining safe thresholds for transfusion is imperative, according to the TRICS III investigators.

“The infections and noninfectious risk associated with transfusion support a restrictive transfusion practice in several clinical settings. However, anemia, particularly in the perioperative setting, may also be detrimental,” C. David Mazer, MD, associate scientist at the Keenan Research Center for Biomedical Science and department of anesthesia at St. Michaels Hospital, Toronto, and colleagues wrote in NEJM. “Patients who are at high perioperative risk may be more susceptible to anemia-induced tissue hypoxia, potentially exposing them to an increased risk of complications and death if a restrictive approach is used.”

During a press conference, Frank W. Sellke, MD, FACS, FAHA, acknowledged the execution and implications of TRICS III.

“We know that that there is a detrimental effect of transfusion and bleeding, both short term and long term,” Sellke, the Karl Karlson and Gloria Karlson Professor and Chief, division of cardiothoracic surgery, and director of the Lifespan Cardiovascular Institute at Brown Medical School and Rhode Island Hospital, said. “We're really looking at the short-term effects and the midterm results, and I'm hoping that the long-term results will be evaluated because this is equally important when you're talking about transfusion thresholds during cardiac surgery.” – by Dave Quaile

References:

Mazer CD. CABG and EP Peri-procedural Dilemmas – LBS.01.

Selke FW. CABG and EP Peri-procedural Dilemmas – LBS.01. Both presented at: American Heart Association Scientific Sessions; Nov. 11-15, 2017; Anaheim, California.

Mazer CD, et al. N Engl J Med. 2017;doi:10.1056/NEJMoa1711818.

Disclosures: The TRICS III trial was funded by the Canadian Institutes of Health Research, Canadian Blood Services Health Canada, National Health and Medical Research Council of Australia, and the Health Research Council of New Zealand. Mazer reports no relevant financial disclosures. Sellke reports he has financial ties with Boehringer Ingelheim, Octapharma and Stryker.

Perspective

Michael Tong, MD, MBA

The most important takeaway is that anemia is generally well-tolerated in cardiac surgery and in an intraoperative and postoperative period, and anemia to a level of 7.5 g/dL seems to be well-tolerated, even in the high-risk group of patients.

Historically, it was always thought that intuitively, if you were anemic enough, your body would not get enough oxygen and you would start to get organ failure. The point where the anemia starts becoming a problem has always been debated. There were not any good studies looking at this question. In the past, patients were transfused at a hemoglobin level around 9 g/dL. However, over the last 20 years, there has been increasing evidence that suggests that the hemoglobin level as low as 7 can be safe. In a randomized controlled trial of 700 patients who underwent CABG or isolated valve surgery and were essentially low-risk, there was no difference in the restrictive and the liberal transfusion groups. The TRICS III trial takes it a step further because it asks the question in high-risk patients and those undergoing more extensive surgery who also may be older and have more comorbidities. Patients in this study had a EUROScore of 6 or more, with an average close to 8. Even in this higher-risk group, a conservative transfusion trigger of 7.5 g/dL still did not impact any clinical outcomes in terms of mortality and morbidity.

We can now conclude that anemia is well-tolerated and we do not have to worry when patient becomes moderately anemic. We can wait until their hemoglobin reaches 7.5 g/dL or below before we transfuse them. Transfusions historically have been associated with infections, lung injury and many other potential complications. There is also a cost to collecting, storing and transfusing blood. If we can safely avoid giving transfusions, ultimately, it is the best for the patient.

The flip side of the coin is that sometimes we worry we are harming patients by giving blood to them, even though they appear to be having symptoms from the anemia and we want to transfuse them to make them feel better. This study shows that if we transfuse patients in those settings, we can feel comfortable that we are not harming patients, because even in the liberal group, there was no difference in hard outcomes.

The conservative transfusion strategy has already been adopted by many groups, especially at high-volume centers. This study gives a lot more data to support that point of view. This is an important step in converting some of the doubters. While 5,000 patients may not seem like a lot compared with medical trials, in cardiac surgery, this is one of the largest randomized clinical trials. It was extremely well-done. From a validity standpoint, it is very strong because it looked at many populations in many locations. This may convert surgeons who may not believe you can get away with a low hemoglobin level.

Michael Tong, MD, MBA

Cardiac Surgeon

Director, Heart Transplantation and Mechanical Circulatory Support

Cleveland Clinic

Disclosures: Tong reports no relevant financial disclosures.