Tight glycemic control after pediatric cardiac surgery in high-risk patient populations: a secondary analysis of the safe pediatric euglycemia after cardiac surgery trial

Abstract

Background: Our previous randomized, clinical trial showed that postoperative tight glycemic control (TGC) for children undergoing cardiac surgery did not reduce the rate of health care-associated infections compared with standard care (STD). Heterogeneity of treatment effect may exist within this population.

Methods and results: We performed a post hoc exploratory analysis of 980 children from birth to 36 months of age at the time of cardiac surgery who were randomized to postoperative TGC or STD in the intensive care unit. Significant interactions were observed between treatment group and both neonate (age ≤30 days; P=0.03) and intraoperative glucocorticoid exposure (P=0.03) on the risk of infection. The rate and incidence of infections in subjects ≤60 days old were significantly increased in the TGC compared with the STD group (rate: 13.5 versus 3.7 infections per 1000 cardiac intensive care unit days, P=0.01; incidence: 13% versus 4%, P=0.02), whereas infections among those >60 days of age were significantly reduced in the TGC compared with the STD group (rate: 5.0 versus 14.1 infections per 1000 cardiac intensive care unit days, P=0.02; incidence: 2% versus 5%, P=0.03); the interaction of treatment group by age subgroup was highly significant (P=0.001). Multivariable logistic regression controlling for the main effects revealed that previous cardiac surgery, chromosomal anomaly, and delayed sternal closure were independently associated with increased risk of infection.

Conclusions: This exploratory analysis demonstrated that TGC may lower the risk of infection in children >60 days of age at the time of cardiac surgery compared with children receiving STD. Meta-analyses of past and ongoing clinical trials are necessary to confirm these findings before clinical practice is altered.

Clinical trial registration url: http://www.clinicaltrials.gov. Unique identifier: NCT00443599.

Keywords: blood glucose; critical care; heart diseases; hyperglycemia; pediatrics.

© 2014 American Heart Association, Inc.

Figures

Figure 1

Exploring the age cutoff. Plot of the log likelihood from logistic regression models, which included the main effects of treatment group and age subgroup (as defined using different age cutoffs) and the interaction term as covariates, versus age cutoff. The maximum likelihood estimate (MLE) is 59 days (confidence interval 55-71 days).

Figure 2

Time-weighted Blood Glucose Average by Day, According to Treatment Group and Age Subgroup. The panels show time-weighted blood glucose averages (TWBA) calculated from all blood glucose samples on the day of post-operative admission to the cardiac intensive care unit (CICU) (day 1) and the subsequent two days (7 a.m. to 6:59 a.m.). Panel A shows the TWGA by day for subjects ≤60 days old at the time of surgery, while Panel B shows the TWGA by day for subjects >60 days old. The points represent the medians, while the error bars extend to the 25th and 75th percentiles. NS denotes not significant.