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Analgesia-Sedation in PICU and Neurological Outcome: A Secondary Analysis of Long-Term Neuropsychological Follow-Up in Meningococcal Septic Shock Survivors*

van Zellem, Lennart MD1; Utens, Elisabeth M. PhD2; de Wildt, Saskia N. MD, PhD1; Vet, Nienke J. MD1; Tibboel, Dick MD, PhD1; Buysse, Corinne MD, PhD1

Pediatric Critical Care Medicine: March 2014 - Volume 15 - Issue 3 - p 189–196
doi: 10.1097/PCC.0000000000000044
Feature Articles

Objectives: To investigate whether analgesic and sedative drug use during PICU treatment is associated with long-term neurodevelopmental outcome in children who survived meningococcal septic shock.

Design: This study concerned a secondary analysis of data from medical and psychological follow-up of a cross-sectional cohort of all consecutive surviving patients with septic shock and purpura requiring intensive care treatment between 1988 and 2001 at the Erasmus MC-Sophia Children’s Hospital. At least 4 years after PICU admission, these children showed impairments on several domains of neuropsychological functioning. In the present study, type, number, and dose of sedatives and analgesics were retrospectively evaluated.

Setting: Tertiary care university hospital.

Patients: Seventy-seven meningococcal septic shock survivors (median age, 2.1 yr).

Interventions: None.

Measurements and Main Results: Forty-five patients (58%) received one or more analgesic and/or sedative drugs during PICU admission, most commonly benzodiazepines (n = 39; 51%), followed by opioids (n = 23; 30%). In total, 12 different kinds of analgesic or sedative drugs were given. The use and dose of opioids were significantly associated with poor test outcome on full-scale intelligence quotient (p = 0.02; Z = –2.28), verbal intelligence quotient (p = 0.02; Z = –2.32), verbal intelligence quotient subtests (verbal comprehension [p = 0.01; Z = –2.56] and vocabulary [p = 0.01; Z = –2.45]), and visual attention/executive functioning (Trial Making Test part B) (p = 0.03; Z = –2.17). In multivariate analysis adjusting for patient and disease characteristics, the use of opioids remained significant on most neuropsychological tests.

Conclusions: The use of opioids during PICU admission was significantly associated with long-term adverse neuropsychological outcome independent of severity of illness scores in meningococcal septic shock survivors.

1Division of Paediatric Intensive Care, Department of Paediatrics, Erasmus MC-Sophia Children’s Hospital, Rotterdam, The Netherlands.

2Department of Child and Adolescent Psychiatry/Psychology, Erasmus MC-Sophia Children’s Hospital, Rotterdam, The Netherlands.

* See also p. 264.

This work was performed at Erasmus MC-Sophia Children’s Hospital, Rotterdam, The Netherlands.

Dr. de Wildt’s institution consulted for the Medicines for Children’s Research Network, Norgine, and Koehler and received grant support from ZonMW, Nuts Ohra, Novartis BV, and EU FP7. The remaining authors disclosed that they do not have any potential conflicts of interest.

For information regarding this article, E-mail: h.vanzellem@erasmusmc.nl

©2014The Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies