Children who received mechanical ventilation at a pediatric intensive care unit (PICU) had slightly worse cognitive outcomes in the long run compared with their siblings, a prospective cohort study found.
At 3 to 8 years after discharge from a PICU, kids who had received mechanical ventilation for acute respiratory failure had a mean estimated IQ of 101.5 versus 104.3 for their matched siblings (mean difference -2.8, 95% CI -5.4 to -0.2), reported R. Scott Watson, MD, MPH, of Seattle Children’s Hospital, and colleagues.
“The magnitude of the difference was small and of uncertain clinical importance,” they noted in JAMA. The study excluded children with severe neurocognitive impairment at discharge, they added.
While “these data provide the strongest evidence to date of the existence and epidemiology of PICS-p [post intensive care syndrome in children] after a single, typical episode of acute respiratory failure necessitating invasive ventilation among generally healthy children,” considering the study’s exclusions, the findings “likely underestimate the true magnitude of PICS-p,” wrote Steven Shein, MD, of Rainbow Babies & Children’s Hospital in Cleveland, and Alexandre Rotta, MD, of Duke University School of Medicine in Durham, North Carolina, in an accompanying editorial.
Nineteen PICU patients who underwent mechanical ventilation had an estimated IQ of ≤85 compared with eight of their siblings (P=0.03), and 20 patients had an estimated IQ score at least 15 points below their siblings versus only nine who scored 15 points above their siblings.
This “demonstrates an overall downward shift in estimated IQ among patients,” Watson and colleagues noted. For context, they pointed out that lead exposure studies report a 6-point IQ shift, but even those “small changes in mean IQ can have important implications depending on the distribution of scores.”
As for secondary outcomes, PICU patients had significantly lower scores than matched siblings on nonverbal memory (mean difference -0.9, 95% CI -1.6 to -0.3), visuospatial skills (mean difference -0.9, 95% CI -1.8 to -0.1), and fine motor control (mean difference -3.1, 95% CI -4.9 to -1.4), and significantly higher scores on processing speed (mean difference 4.4, 95% CI 0.2-8.5). There were no significant differences in other secondary outcomes, including attention, verbal memory, expressive language, and executive function.
“Because of the potential for type I error due to multiple comparisons, findings for analyses of secondary endpoints should be interpreted as exploratory,” Watson and team wrote.
The study also showed that patients who were hospitalized at younger ages had worse outcomes. Those who scored “substantially lower” than their siblings had a median age of 2 months at PICU admission, while those who scored the same as or higher than their siblings had a median age of 1.4 years (mean difference -1.3 years, 95% CI -2.3 to -0.2), the study group said.
“These results suggest that the developing brain may be more susceptible to injury related to critical illness and associated therapies,” Shein and Rotta wrote. They noted that while a 2019 study suggested that general anesthesia in early infancy was not harmful in the long run, this analysis shows that might not be the case for children admitted to the PICU.
Watson and colleagues explained that children admitted to the PICU may receive days of anesthetics, while many hospitalized children may only receive them for a few hours.
In 2017, the FDA released a warning about anesthesia use in children younger than 3 years.
From 2014 to 2018, 121 sibling pairs were tested, with 116 included in the primary outcome analysis. Two-thirds of the study population were white, 55 patients and 72 siblings were girls, and most generally came from middle and upper-middle-class families. Sixty-nine percent of patients were younger than their matched sibling.
Patients were included if they were 8 years old or younger at the beginning of the trial, had a Pediatric Cerebral Performance Category (PCPC) score of 1 (indicating normal neurocognitive function) prior to PICU admission, and a PCPC score ≤3 (no worse than moderate neurocognitive dysfunction) at discharge. Patients with a history of conditions associated with neurocognitive deficits were excluded.
Siblings were eligible if they were ages 4 to 16 at the time of neurocognitive testing, had a PCPC score of 1, and had the same biological parents as the patient and lived with the patient.
Patients were treated in the PICU at a median age of 1.0 years (interquartile range [IQR] 0.2-3.2), and patient follow-up occurred at a median age of 6.6 years (IQR 5.4-9.1). The most common respiratory conditions requiring PICU admission were bronchiolitis or asthma (44%) and pneumonia (37%).
IQ was estimated using age-appropriate Vocabulary and Block Design subtests of the Wechsler Intelligence Scale as surrogates for the full-scale IQ test.
Watson and colleagues acknowledged that they relied on sibling comparisons, since they were unable to compare pre-PICU IQ with post-PICU IQ.
The study was funded by grants from the Eunice Kennedy Shriver National Institute of Child Health and Human Development.
The study authors reported no disclosures. Rotta reported fees from Vapotherm Inc and Breas U.S., as well as royalties from Elsevier.