R Scott Watson1,2, Sue R Beers3, Lisa A Asaro4, Cheryl Burns5, Min Jung Koh6, Mallory A Perry7, Derek C Angus8,9, David Wypij4,6,10, Martha A Q Curley7,11. 1. Department of Pediatrics, University of Washington, Seattle. 2. Center for Child Health, Behavior, and Development, Seattle Children's Research Institute, Seattle, Washington. 3. Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania. 4. Department of Cardiology, Boston Children's Hospital, Boston, Massachusetts. 5. University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania. 6. Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, Massachusetts. 7. Research Institute, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania. 8. Clinical Research, Investigation, and Systems Modeling of Acute Illness Center, Department of Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania. 9. Senior Editor, JAMA. 10. Department of Pediatrics, Harvard Medical School, Boston, Massachusetts. 11. Department of Family and Community Health, School of Nursing, University of Pennsylvania, Philadelphia.
Abstract
Importance: Approximately 23 700 US children undergo invasive mechanical ventilation for acute respiratory failure annually, with unknown long-term effects on neurocognitive function. Objective: To evaluate neurocognitive outcomes of children who survive pediatric intensive care unit (PICU) hospitalization for acute respiratory failure compared with their biological siblings. Design, Setting, and Participants: Prospective sibling-matched cohort study conducted at 31 US PICUs and associated neuropsychology testing centers. Patients were 8 years or younger with a Pediatric Cerebral Performance Category score of 1 (normal) before PICU admission and less than or equal to 3 (no worse than moderate neurocognitive dysfunction) at PICU discharge, excluding patients with a history of neurocognitive deficits or who were readmitted and underwent mechanical ventilation. Biological siblings were aged 4 to 16 years at testing, with Pediatric Cerebral Performance Category score of 1 and no history of mechanical ventilation or general anesthesia. A total of 121 sibling pairs were enrolled from September 2, 2014, to December 13, 2017, and underwent neurocognitive testing starting March 14, 2015. The date of the final follow-up was November 6, 2018. Exposures: Critical illness and PICU treatment for acute respiratory failure. Main Outcomes and Measures: The primary outcome was IQ, estimated by the age-appropriate Vocabulary and Block Design subtests of the Wechsler Intelligence Scale. Secondary outcomes included measures of attention, processing speed, learning and memory, visuospatial skills, motor skills, language, and executive function. Evaluations occurred 3 to 8 years after hospital discharge. Results: Patients (n = 121; 55 [45%] female patients) underwent PICU care at a median (IQR) age of 1.0 (0.2-3.2) years, received a median (IQR) of 5.5 (3.1-7.7) days of invasive mechanical ventilation, and were tested at a median (IQR) age of 6.6 (5.4-9.1) years. Matched siblings (n = 121; 72 [60%] female siblings) were tested at a median (IQR) age of 8.4 (7.0-10.2) years. Patients had a lower mean estimated IQ than matched siblings (101.5 vs 104.3; mean difference, -2.8 [95% CI, -5.4 to -0.2]). Among secondary outcomes, 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 the remaining secondary outcomes, including attention, verbal memory, expressive language, and executive function. Conclusions and Relevance: Among children, survival of PICU hospitalization for respiratory failure and discharge without severe cognitive dysfunction was associated with significantly lower subsequent IQ scores compared with matched siblings. However, the magnitude of the difference was small and of uncertain clinical importance.
Importance: Approximately 23 700 US children undergo invasive mechanical ventilation for acute respiratory failure annually, with unknown long-term effects on neurocognitive function. Objective: To evaluate neurocognitive outcomes of children who survive pediatric intensive care unit (PICU) hospitalization for acute respiratory failure compared with their biological siblings. Design, Setting, and Participants: Prospective sibling-matched cohort study conducted at 31 US PICUs and associated neuropsychology testing centers. Patients were 8 years or younger with a Pediatric Cerebral Performance Category score of 1 (normal) before PICU admission and less than or equal to 3 (no worse than moderate neurocognitive dysfunction) at PICU discharge, excluding patients with a history of neurocognitive deficits or who were readmitted and underwent mechanical ventilation. Biological siblings were aged 4 to 16 years at testing, with Pediatric Cerebral Performance Category score of 1 and no history of mechanical ventilation or general anesthesia. A total of 121 sibling pairs were enrolled from September 2, 2014, to December 13, 2017, and underwent neurocognitive testing starting March 14, 2015. The date of the final follow-up was November 6, 2018. Exposures: Critical illness and PICU treatment for acute respiratory failure. Main Outcomes and Measures: The primary outcome was IQ, estimated by the age-appropriate Vocabulary and Block Design subtests of the Wechsler Intelligence Scale. Secondary outcomes included measures of attention, processing speed, learning and memory, visuospatial skills, motor skills, language, and executive function. Evaluations occurred 3 to 8 years after hospital discharge. Results: Patients (n = 121; 55 [45%] female patients) underwent PICU care at a median (IQR) age of 1.0 (0.2-3.2) years, received a median (IQR) of 5.5 (3.1-7.7) days of invasive mechanical ventilation, and were tested at a median (IQR) age of 6.6 (5.4-9.1) years. Matched siblings (n = 121; 72 [60%] female siblings) were tested at a median (IQR) age of 8.4 (7.0-10.2) years. Patients had a lower mean estimated IQ than matched siblings (101.5 vs 104.3; mean difference, -2.8 [95% CI, -5.4 to -0.2]). Among secondary outcomes, 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 the remaining secondary outcomes, including attention, verbal memory, expressive language, and executive function. Conclusions and Relevance: Among children, survival of PICU hospitalization for respiratory failure and discharge without severe cognitive dysfunction was associated with significantly lower subsequent IQ scores compared with matched siblings. However, the magnitude of the difference was small and of uncertain clinical importance.
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