Factors Associated With Neurobehavioral Complications in Pediatric Abdominal Organ Transplant Recipients Identified Using Computable Composite Definitions

Abstract

Objectives: Neurologic complications occur in up to 40% of adult abdominal solid organ transplant recipients and are associated with increased mortality. Comparable pediatric data are sparse. This study describes the occurrence of neurologic and behavioral complications (neurobehavioral complications) in pediatric abdominal solid organ transplant recipients. We examine the association of these complications with length of stay, mortality, and tacrolimus levels.

Design: The electronic health record was interrogated for inpatient readmissions of pediatric abdominal solid organ transplant recipients from 2009 to 2017. A computable composite definition of neurobehavioral complication, defined using structured electronic data for neurologic and/or behavioral phenotypes, was created.

Setting: Quaternary children's hospital with an active transplant program.

Patients: Pediatric abdominal solid organ transplant recipients.

Interventions: None.

Measurements and main results: Computable phenotypes demonstrated a specificity 98.7% and sensitivity of 63.0% for identifying neurobehavioral complications. There were 1,542 readmissions among 318 patients, with 65 (20.4%) having at least one admission with a neurobehavioral complication (total 109 admissions). Median time from transplant to admission with neurobehavioral complication was 1.2 years (interquartile range, 0.52-2.28 yr). Compared to encounters without an identified neurobehavioral complication, encounters with a neurobehavioral complication were more likely to experience ICU admission (odds ratio, 3.9; 2.41-6.64; p < 0.001), have longer ICU length of stay (median 10.3 vs 2.2 d; p < 0.001) and hospital length of stay (8.9 vs 4.3 d; p < 0.001), and demonstrate higher maximum tacrolimus level (12.3 vs 9.8 ng/mL; p = 0.001). Patients with a neurobehavioral complication admission were more likely to die (odds ratio, 5.04; 1.49-17.09; p = 0.009). In a multivariable analysis, type of transplant, ICU admission, and tacrolimus levels were independently associated with the presence of a neurobehavioral complication.

Conclusions: Common electronic health record variables can be used to accurately identify neurobehavioral complications in the pediatric abdominal solid organ transplant population. Late neurobehavioral complications are associated with increased hospital resource utilization, mortality, and tacrolimus exposure. Additional studies are required to delineate the relationship between maximum tacrolimus level and neurobehavioral complications to guide therapeutic drug monitoring and dosing.

Figure 1.

Flow diagram of the study population and included admissions

Figure 2.

Proportion of patients with an identified neurobehavioral complication admission based on the number of readmissions. NBC = neurobehavioral complication

Figure 3.

Maximum tacrolimus levels between (A) admissions with and without an identified neurobehavioral complication and (B) admissions with and without one of the three different neurobehavioral complication phenotypes. Note: There is one value of 80 ng/ml not shown for admissions without a neurobehavioral complication in both figures. *P=0.001, ^†P<0.001. NBC = neurobehavioral complication.

Figure 3.

Maximum tacrolimus levels between (A) admissions with and without an identified neurobehavioral complication and (B) admissions with and without one of the three different neurobehavioral complication phenotypes. Note: There is one value of 80 ng/ml not shown for admissions without a neurobehavioral complication in both figures. *P=0.001, ^†P<0.001. NBC = neurobehavioral complication.