Heart surgery

Steroids offer no clear benefit in pediatric cardiac surgery

The decades-old question of whether steroids should be used in infants undergoing heart surgery to reduce inflammation from cardiopulmonary bypass remains unanswered, despite the weight of the largest pediatric heart surgery trial to date.

Results from the STRESS trial, which included 1200 babies who had not yet reached their first birthday, show that perioperative methylprednisolone did not reduce the likelihood of a graded composite of outcomes including operative death, heart transplantation, and 13 other major complications compared to placebo after adjusting for covariates (adjusted odds ratio [OR] 0.86; 95% CI, 0.71 – 1.05).

There were no differences in the major components of the endpoint of operative mortality (2% in the methylprednisolone group versus 2.8% in the placebo group), a composite of mortality and major complications (17.2% versus 20.3%) and prolonged mechanical ventilation (6.8% versus 8.5%).

Babies who received methylprednisolone were also more likely to have high blood sugar, a known stress reaction to surgery, with 19% of them requiring postoperative insulin compared to 6.7% with placebo (P New England Journal of Medicine.

In a secondary analysis, however, methylprednisolone reduced the odds of the primary endpoint when analyzed without covariate adjustment (OR, 0.82; 95% CI, 0.67, 1.00) and was a ‘victory’ for babies in a success ratio analysis of matched pairs of patients (1.15; 95% CI 1.00, 1.32).

The odds of bleeding requiring reoperation were also significantly lower in the steroid group (7 events versus 21; aOR, 0.34; P = 0.016).

“There are a lot of signals suggesting a small benefit from steroids, so in talking with our surgeons, I suggested we continue using them,” said lead researcher Kevin D. Hill, MD, Duke Pediatric and Congenital Heart. Center in Durham, North Carolina, says lecoeur.org | Medscape Cardiology.

“But I think it’s possible to use them in a more targeted way for patients who have more potential for benefit and less potential for side effects,” he added.

Subgroup analyzes suggested relatively greater benefit for infants undergoing less complex operations (STAT 1-3 on a 5-point scale), those with longer cardiopulmonary bypass times, and those born preterm.

Lack of evidence

“We love to see a trial where treatments hit a home run and are something we can do for our patients that makes a really big difference. Unfortunately, that’s not the case here,” Larry A. Allen, MD, University of Colorado, Aurora, says lecoeur.org | Medscape Cardiology.

“It’s one of those trials where it’s trending in the right direction but isn’t statistically significant, so the bottom line is there may be a small benefit, it’s not big and it probably doesn’t cause not much harm,” he said. “So we’re left to say that the current practice is probably reasonable.”

Presenting the results at the American Heart Association’s 2022 Scientific Sessions, Hill pointed out that previous studies of perioperative corticosteroids in children suggested a mortality benefit, while a recent meta-analysis only reported no difference in outcomes other than improved water balance at 24 and 36 hours. , but was undernourished with only 768 children enrolled over four decades.

Not surprisingly, 52% of newborns undergoing heart surgery receive steroids and 48% do not, he said.

STRESS was a pragmatic trial recruiting children under 1 year of age undergoing elective cardiopulmonary bypass surgery at 24 sites in the Society of Thoracic Surgeons Congenital Surgery database. An auxiliary database was also created to track results.

A total of 1263 patients were randomly assigned to methylprednisolone 30 mg/kg or placebo, of whom 1200 received study treatment. The median age was 126 days and three quarters were white.

“Our pragmatic ‘trial in a registry’ design was successful with a total cost of approximately $3 million or $2400 per patient, which is significantly lower than any traditional trial,” Hill said.

The future of pediatric trials

Guest commentator Stephanie Fuller, MD, Children’s Hospital of Philadelphia, Philadelphia, PA, noted that the trial took place over 6 years at 24 centers and that “estimated costs were less than $3 million and you estimate the cost of a conventional trial similar to this would be around $13 million. This is truly the future of pediatric cardiovascular trials.

Patrick O’Gara, MD, of Brigham and Women’s Hospital, Boston, Massachusetts, and co-moderator of the late-breaking session, said in an interview that “one of the most important things about this trial was the demonstration that we can actually do a randomized trial in a registry-based format and move forward in the field of pragmatic trials that answer these major clinical questions.

As for how the results will be interpreted, “I think it will come down to parochial preferences, as a lot of these things do.”

Alistair Phillips, MD, Cleveland Clinic Miller Family Heart and Vascular Institute, Ohio, said lecoeur.org | Medscape Cardiology that the STRESS is an “important and very well done study whose major issue is the heterogeneity of the population and the variability of care from one institution to another, from anesthesia techniques to infusion techniques, and blood management techniques to postoperative medical management”. to examine specific populations are warranted. »

The study was funded by the Centers for Advancing Translational Sciences and the Eunice Kennedy Shriver National Institute of Child Health and Human Development. Hill reports no relevant industry relationships.

N Engl J Med. Published November 6, 2022. Full text

2022 American Heart Association (AHA) Scientific Sessions. Presented November 6, 2022.

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