Administration of Steroids in Infants during CPB: Common Practice with No Evidence.

Viviane Nasr, Susan Nicolson, Lindsey Loveland Baptist, James DiNardo

For many thousands of years bloodletting was one of the primary therapies offered by doctors to cure patients of myriad diseases like gout, fevers, seizures, infections, and cancer. Indeed, George Washington died of hypovolemic shock when he was treated for epiglottitis by blood letting. Fortunately, bloodletting is mostly an abandoned practice, except of course if you are an adult inpatient in the hospital getting daily blood tests or getting hot cupping on your back prior to Olympic swimming races…but I digress.  When bloodletting was abandoned another practice that doctors used when they didn’t have any better ideas was/is to treat illness with steroids. Indeed, we still use steroids even when no evidence supports its use. Just think of spinal cord injury or as a prophylactic in pediatric open heart surgery. Today’s PAAD written by the PAAD’s incomparable cardiac team hopefully puts the nail in the coffin for steroid use in children undergoing heart surgery.  Myron Yaster MD

Original article

Hill KD, Kannankeril PJ, Jacobs JP, Baldwin HS, Jacobs ML, O'Brien SM, Bichel DP, Graham EM, Blasiole B, Resheidat A, Husain AS, Kumar SR, Kirchner JL, Gallup DS, Turek JW, Bleiweis M, Mettler B, Benscoter A, Wald E, Karamlou T, Van Bergen AH, Overman D, Eghtesady P, Butts R, Kim JS, Scott JP, Anderson BR, Swartz MF, McConnell PI, Vener DF, Li JS; STRESS Network Investigators. Methylprednisolone for Heart Surgery in Infants - A Randomized, Controlled Trial. N Engl J Med. 2022 Nov 6. doi: 10.1056/NEJMoa2212667. Epub ahead of print. PMID: 36342116.

Steroids administration during cardiopulmonary bypass (CPB) in infants is a long-standing practice in cardiac surgery. However, three meta-analyses evaluating the outcomes of steroids in children reported conflicting results with one demonstrating lower mortality and two demonstrating no difference in outcome.

Recently, using the STS-CHSD registry, Hill et al. conducted a randomized trial comparing infants (<1 year of age) who received methylprednisolone at a dose of 30 mg per kilogram of body weight vs. placebo.  The methylprednisolone and placebo were administered into the pump CPB-priming fluid. Twenty-four sites participated in the study.

The primary end point was a composite outcome of death defined as mortality during the initial hospitalization or within 30 days after the surgery if discharged, heart transplantation during hospitalization or any of 13 major complications; kidney failure with permanent or temporary dialysis, neurologic deficit persistent at discharge, respiratory failure warranting tracheostomy, postoperative mechanical circulatory support, mechanical ventilator support for more than 7 days, unplanned cardiac reoperation, unplanned delayed sternal closure, unplanned interventional cardiac catheterization after surgery, postoperative cardiac arrest, and multisystem organ failure. Patients who did not suffer any of those events were assigned a ranked outcome based on postoperative length of stay.

There were 599 infants in the methylprednisolone group and 601 infants in the placebo group. The likelihood of a primary outcome did not differ significantly between the methylprednisolone and the placebo groups (adjusted odds ratio, 0.86; 95% confidence interval [CI], 0.71 to 1.05; p=0.14). This result is similar to that seen in previous studies in both adults and children. The two largest adult trials, the Dexamethasone for Cardiac Surgery (DECS) and the Steroids in Cardiac Surgery (SIRS) trials, showed no mortality benefit associated with prophylactic use of glucocorticoids. The lack of an effect of methylprednisolone on the primary outcome of mortality are also consistent with those in the two most recent and largest pediatric trials: the Dexamethasone in Pediatric Cardiac Surgery (DECISION) trial and the trial by Graham et al. An anticipated side effect of methylprednisolone administration is hyperglycemia. Patients in the methylprednisolone group were more likely than those in the placebo group to receive postoperative insulin for hyperglycemia (19% vs. 6.7%, p<0.001).

Based on this study and previous studies the love-affair with steroid administration in this setting should likely end. More than likely, it will not and the forlorn will pin their hopes on the results of the unadjusted analysis which demonstrated a possible benefit of methylprednisolone administration. The odds ratio for a worse outcome was 0.82 (95% CI, 0.67 to 1.00) and the win ratio was 1.15 (95% CI, 1.00 to 1.32) in the methylprednisolone group as compared with the placebo group. The win ratio is not the chance of the U.S. winning the World Cup; it is calculated by forming all possible pairs consisting  of  one  patient  from  the  methylprednisolone group and one from the placebo group, then dividing the number of pairs in which the patient  in  the  methylprednisolone  group  has  a  better  outcome  than  the  patient  in  the  placebo  group  (a  win)  by  the  number  of  pairs  in  which  the  opposite  occurs  (a  loss). 

References:

1.     Whitlock RP, Devereaux PJ, Teoh KH, et al. Methylprednisolone in patients undergoing cardiopulmonary bypass (SIRS): a randomised, double-blind, placebo-controlled trial. Lancet 2015; 386: 1243-53.

2.    Dieleman JM, Nierich AP, Rosseel PM, et al. Intraoperative high-dose dexamethasone for cardiac surgery: a randomized controlled trial. JAMA 2012; 308: 1761-7.

3.    Lomivorotov V, Kornilov I, Boboshko V, et al. Effect of intraoperative dexamethasone on major complications and mortality among infants undergoing cardiac surgery: the DECISION randomized clinical trial. JAMA 2020; 323: 2485-92.

4.    Graham EM, Martin RH, Buckley JR, et al. Corticosteroid therapy in neonates undergoing cardiopulmonary bypass: randomized controlled trial. J Am Coll Cardiol 2019; 74: 659-68.