Children who undergo cardiac surgery may suffer predictable systemic inflammatory responses, myocardial depression, and pulmonary endothelial dysfunction, all related to ischemia-reperfusion (IR) injury and cardiopulmonary bypass (CPB). One therapeutic strategy to prevent these injuries involves remote ischemic preconditioning (RIC), whereby a remote organ (usually a limb) is made repeatedly ischemic and then reperfused over a short period before the more significant IR insult (like cardiac surgery). This practice has been shown to modify the expression of key proteins in cytokine synthesis and leukocyte trafficking. Cheung et al demonstrated that RIC, applied prior to the initiation of CPB, provided some myocardial protection in children who underwent cardiac surgery.
In the August issue of Pediatric Anesthesia Zhong et al applied the same principles, though the timing of ischemia was different. The authors recruited 69 subjects (35 in the control group and 34 in the ischemic group) between the ages of 3 and 12 years who underwent repair of their congenital heart diseases. Remote ischemia was achieved by inflating a blood pressure cuff located on a lower limb to a pressure of 200 mm Hg for 5 minutes, followed by deflation for 5 minutes; this was repeated for a total of 3 cycles. These maneuvers were performed after the aorta was unclamped. The primary endpoint the maneuver’s effect on cardiac troponin I levels over 24 hours. Secondary endpoints included clinical outcomes, adverse cardiac events and changes in other metabolic markers such as neuron-specific enolase.
Like other researchers, Zhong et al were able to demonstrate that subjects who underwent remote ischemia had lower levels of troponin and creatine kinase-MB postoperatively compared to controls. These subjects also had better blood pressure levels and shorter lengths of hospital stay compared to control subjects. Cytokine levels and other metabolic markers were not different between the groups.
Although these data are encouraging, some points need to be considered. Jones et al recently published their randomized controlled trial looking at the cardiac and neurologic effects of RIC after surgical repair in cyanotic infants with either transposition of the great arteries or hypoplastic left heart syndrome. This population was chosen because of the unique risks these infants experienced from IR injury and CPB. Unlike the results of Zhong et al, those of Jones’s group did not demonstrate any significant improvement in metabolic markers or clinical outcomes. Children with cyanotic heart disease may respond to IR injury differently than those studied by Zhong et al. Another possibility may be related to the ages of the patients.
Remote ischemia is proving to be an area of active study and may play an important role in the future for children undergoing repair of congenital heart diseases. More research should delineate the best patient population and the optimal timing for this strategy.
This Concise Critical Appraisal is authored by SCCM member Daniel E. Sloniewsky, MD. Each installment highlights journal articles most relevant to the critical care practitioner. Daniel Sloniewsky is an Associate Professor in the Department of Pediatrics at the Stony Brook Long Island Children’s Hospital in Stony Brook, NY, where he is board certified in Pediatrics and Pediatric Critical Care. He completed his Fellowship training at Children’s Memorial Hospital and Northwestern University in Chicago. His major interests are in acute pediatric pulmonary disease, transfusion medicine and ethics. He is also actively involved in resident education, Pediatric Advanced Life Support and Pediatric FCCS instruction.