December 30, 2022

Study Suggests Incremental Benefit for Steroid Use in Infant Heart Surgery

Surgeons reassured by low risk of harm

22-CHP-3416348 CQD- Karamlou – Methylprednisolone for Infant Heart-650×450

Use of steroids in infants undergoing heart surgery with cardiopulmonary bypass is a routine practice designed to reduce inflammation and improve the likelihood of a smooth recovery. Whether it causes harm has been debated. Now, the largest randomized, prospective, controlled clinical trial ever conducted in pediatric cardiac surgery has put the issue to rest.


Cleveland Clinic is a non-profit academic medical center. Advertising on our site helps support our mission. We do not endorse non-Cleveland Clinic products or services. Policy

“The answer is no,” says Tara Karamlou, MD, a pediatric and congenital heart surgeon at Cleveland Clinic Children’s who participated in the Steroids to Reduce Systemic Inflammation after Infant Heart Surgery (STRESS) trial. “I think it demonstrated that centers can use steroids in these highly complex patient populations without fear of deleterious things happening down the road.”

Gauging benefit

STRESS was a prospective, placebo-controlled, registry-based trial that randomized 1200 of 1263 infants less than 1 year of age undergoing heart surgery with cardiopulmonary bypass at 24 sites to receive prophylactic methylprednisone (30 mg/kg of body weight) or placebo in the pump-priming fluid. Results were published in the New England Journal of Medicine on Nov. 6, 2022.

The primary endpoint was a composite of death, heart transplantation or any of 13 major complications. The likelihood of a worse outcome did not differ significantly between the steroid group and the placebo group. However, need for postoperative insulin for hyperglycemia was greater in the steroid group (19% vs. 6.7%).

The unadjusted secondary analyses showed an odds ratio for a worse outcome to be 0.82 and a win ratio of 1.15 in the methylprednisone group, compared with the placebo group. These findings demonstrate a benefit with steroids that Dr. Karamlou says should not be discounted.

“I feel there is probably an incremental advantage to using steroids in populations that are too small to study as individual subsets,” she says. “Some covariables may be obscuring the benefit. It’s an aggregate population, so in a large trial like this you may lose the ability to discern benefit in key populations.”

Feeling reassured

Dr. Karamlou was not deterred by the slight increase in risk of hyperglycemia, as it may be resolved with a small amount of insulin.


The main message was that no adverse effects from methylprednisone were seen. This is important to centers like Cleveland Clinic that use methylprednisone in all babies, including neonates, requiring cardiopulmonary bypass.

“Steroids have a lot of systemic effects, but they are the best tool we have to avoid the deleterious effects of cardiopulmonary bypass in small babies. Steroids may improve the perioperative convalescence of patients following open heart surgery because they often expedite the ability to get patients extubated, have their sternum closed and leave the ICU,” she says.

While most centers follow the STRESS trial protocol and give a single dose of steroids in the pump prime, Cleveland Clinic normally gives a dose the evening before surgery and another dose in the pump prime.

“Some centers give three doses, adding the third eight to 10 hours after surgery. We don’t do the post-surgical dose, but we will continue giving our neonatal patients steroids in the pump prime and also the evening before surgery,” says Dr. Karamlou.

Win-win trial design

A tangential benefit of STRESS was its successful construct as a trial within a registry. Participants in all 24 sites were enrolled in the Society of Thoracic Surgeons Congenital Heart Surgery Database. This reduced the costs of the study from an estimated $10 million to $3.2 million.

Dr. Karamlou calls the concept and execution of the study “transformative.”


“Pediatric heart surgery is a resource-limited enterprise. Most pediatric cardiac surgery is a money-loser considering 90% of reimbursement in most states comes from Medicaid,” she says.

“Executing a randomized trial using registry data, and having it validated within the context of a National Institutes of Health-funded prospective, placebo-controlled trial has never been done before.

“The ability to conduct this type of trial at a reduced cost is critical for pushing the needle on our specialty forward,” she says.

Related Articles

650×450-Hopkins-ENT (002)
November 22, 2022
A Medical Home for Pediatric Patients With Complex Aerodigestive Issues

Multidisciplinary team coordinates, adds efficiencies to care

Surgeon wearing a surgical cap, glasses and mask
February 19, 2024
New Recommendations for Pediatric Cardiac Surgery for Congenital Heart Disease

Expert panel advises a two-tier structure for surgical centers

23-CHP-3889480 CQD Najm- AATS Presentation
August 15, 2023
Novel Double-Shunt Procedure for Rare Congenital Heart Disease Precludes Infant From Heart Transplant

Case is first of its kind to obviate heart transplant successfully

23-CHP-3711810 CQD Tretter
May 23, 2023
Cardiac Pathology Study Targets Conduction Axis Vulnerability

New findings on aortic root position and features may lead to safer valvar surgery

March 25, 2022
Approach May Minimize Need for Subsequent Surgeries in Pediatric Congenital Heart Disease

Several factors identified that may reduce the need for open-heart surgery in some infants

November 19, 2021
Socioeconomic and Racial Disparities in Congenital Heart Disease Outcomes

Findings from a national database study

Smiling child in green shirt with superimposed outline of the lymphatic system
February 27, 2024
Trials to Study Use of 2 Cancer Drugs in Patients With Lymphatic Malformations

Genetic changes are similar between some vascular anomalies and cancers

Surgeon wearing a surgical cap and mask
February 15, 2024
Minimally Invasive Surgery in Neonates: Q&A With Miguel Guelfand, MD

Our new head of pediatric general and thoracic surgery shares his passion and vision