To a greater extent than any of us would prefer, medicine is often practiced by habit. We do things the way they’ve always been done – because it’s the way they’ve always been done. Luckily, a fresh voice sometimes challenges the status quo and leads us toward improved practices. Such is the case for Dr. Alexa Craig and the strategy for rewarming babies following cardiac surgery.
An infant undergoing open heart surgery is typically cooled intraoperatively by the cardiopulmonary bypass machine. This therapeutic hypothermia protects the infant’s brain by decreasing cerebral metabolism, reducing free-radical-mediated pathology, and several other mechanisms. Upon completion of surgery, the infants are typically rapidly rewarmed over the course of about 15 minutes. However, this rapid rewarming can be associated with rebound hyperthermia, which animal data suggest may diminish or even negate the neuroprotective effect of the intraoperative cooling.
Dr. Craig has hypothesized that a slower, incremental rewarming protocol may improve neurodevelopmental outcomes among infants undergoing cardiopulmonary bypass.
As a neonatal neurologist, Dr. Alexa Craig recognized that this rapid rewarming approach conflicts with the strategy used in the treatment of neonatal encephalopathy, where infants are rewarmed much more slowly – over the course of 12 hours – with a servo-controlled temperature regulation blanket. She further recognized that infants undergoing cardiopulmonary bypass surgery have disproportionately poor developmental outcomes. Research update: That’s cool! Improving post-op outcomes of infants with delayed rewarming.
Thus, Dr. Craig has hypothesized that a slower, incremental rewarming protocol may improve neurodevelopmental outcomes among infants undergoing cardiopulmonary bypass.
Dr. Craig is first testing the safety of slowed rewarming by conducting a pilot clinical study at Maine Medical Center, where she is a staff physician and an Assistant Professor at the Tufts University School of Medicine. In this non-blinded, randomized, pilot study, Dr. Craig is assigning infants to the standard of care group, in which they are rewarmed to 36.5 degrees on bypass or to the experimental group, in which they are rewarmed to 35 degrees on bypass, and then slowly rewarmed to 36.5 degrees over the next 12 hours.
In addition to measuring safety, Dr. Craig is also assessing neuroprotection of the delayed rewarming protocol by collecting serum biomarkers of brain injury. These include s100b and neuron specific enolase, which are released into serum from glia and neurons following cellular injury. Preliminary data suggest that one advantage of this protocol is the avoidance of rebound hyperthermia (see figure).
If Dr. Craig’s project is successful, then future research will assess the impact of further prolonging exposure to mild systemic hypothermia. Ultimately, she hopes to design a multi-center randomized trial to determine the most effective temperature management strategy for children undergoing bypass surgery. In the same way that therapeutic hypothermia has improved outcomes for newborns with encephalopathy, controlled temperature regulation may do the same for babies with congenital heart disease. Dr. Craig’s research is funded by a Charleton Award from Tuft’s University and by an NIH KL2 award.
Figure legend: Body temperatures over time among individual babies assigned to the slowed rewarming group (blue lines) and standard of care group (red lines). While both of the babies in the standard of care (control) group had fevers (temperatures above 38.5 degrees), none of the five babies in the experimental group did. Thus, slowed rewarming may prevent rebound hyperthermia.