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J Pediatr Intensive Care 2020; 09(04): 271-276
DOI: 10.1055/s-0040-1712144
Original Article

Exposure to Anticholinergic Medications in Pediatric Severe Sepsis and Feasibility of Delirium Screening

Kate Madden 
1   Department of Anesthesiology, Critical Care and Pain Medicine, Boston Children's Hospital, Boston, Massachusetts, United States
,
Charles G. Callif 
1   Department of Anesthesiology, Critical Care and Pain Medicine, Boston Children's Hospital, Boston, Massachusetts, United States
,
Robert C. Tasker
1   Department of Anesthesiology, Critical Care and Pain Medicine, Boston Children's Hospital, Boston, Massachusetts, United States
2   Department of Neurology, Boston Children's Hospital, Boston, Massachusetts, United States
› Author Affiliations Funding The authors acknowledge that an internal award from the Department of Anesthesiology, Critical Care and Pain Medicine, Boston Children's Hospital has been used for this article.
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Abstract

In sepsis, anticholinergic dysregulation may result in encephalopathy or delirium during severe illness, either as a result of central inflammation or because of exposure to medications with anticholinergic activity. In this retrospective study, we determined the magnitude of anticholinergic drug exposure in 75 children with severe sepsis. We found that exposure over the first 5 days was high—median (interquartile range) daily anticholinergic drug scale score 4 (2–5)—and associated with higher vasoactive scores and death. We conclude that anticholinergic drug exposure is significant in severe sepsis, which means it may be a modifiable factor that should be studied further.

Keywords

anticholinergic - delirium - sepsis - sepsis-associated encephalopathy


Publication History

Received: 13 January 2020

Accepted: 17 April 2020

Article published online:
01 June 2020

© 2020. Thieme. All rights reserved.

Georg Thieme Verlag KG
Stuttgart · New York

 

  • References

  • 1 Sonneville R, de Montmollin E, Poujade J. et al. Potentially modifiable factors contributing to sepsis-associated encephalopathy. Intensive Care Med 2017; 43 (08) 1075-1084
    CrossrefPubMedGoogle Scholar
  • 2 Robba C, Crippa IA, Taccone FS. Septic encephalopathy. Curr Neurol Neurosci Rep 2018; 18 (12) 82
    CrossrefPubMedGoogle Scholar
  • 3 van Gool WA, van de Beek D, Eikelenboom P. Systemic infection and delirium: when cytokines and acetylcholine collide. Lancet 2010; 375 (9716): 773-775
    CrossrefPubMedGoogle Scholar
  • 4 Gofton TE, Young GB. Sepsis-associated encephalopathy. Nat Rev Neurol 2012; 8 (10) 557-566
    CrossrefPubMedGoogle Scholar
  • 5 Sandquist MK, Clee MS, Patel SK. et al. High frequency of neuroimaging abnormalities among pediatric patients with sepsis who undergo neuroimaging. Pediatr Crit Care Med 2017; 18 (07) 607-613
    CrossrefPubMedGoogle Scholar
  • 6 Sanz D, D'Arco F, Robles CA, Brierley J. Incidence and pattern of brain lesions in paediatric septic shock patients. Br J Radiol 2018; 91 (1084): 20170861
    CrossrefPubMedGoogle Scholar
  • 7 Garralda ME, Gledhill J, Nadel S, Neasham D, O'Connor M, Shears D. Longer-term psychiatric adjustment of children and parents after meningococcal disease. Pediatr Crit Care Med 2009; 10 (06) 675-680
    CrossrefPubMedGoogle Scholar
  • 8 Als LC, Picouto MD, Hau SM. et al. Mental and physical well-being following admission to pediatric intensive care. Pediatr Crit Care Med 2015; 16 (05) e141-e149
    CrossrefPubMedGoogle Scholar
  • 9 Cerejeira J, Batista P, Nogueira V, Firmino H, Vaz-Serra A, Mukaetova-Ladinska EB. Low preoperative plasma cholinesterase activity as a risk marker of postoperative delirium in elderly patients. Age Ageing 2011; 40 (05) 621-626
    CrossrefPubMedGoogle Scholar
  • 10 Tune L, Coyle JT. Serum levels of anticholinergic drugs in treatment of acute extrapyramidal side effects. Arch Gen Psychiatry 1980; 37 (03) 293-297
    CrossrefPubMedGoogle Scholar
  • 11 Tsuruta R, Girard TD, Ely EW. et al. Associations between markers of inflammation and cholinergic blockade and delirium in intensive care unit patients: a pilot study. Bull Yamaguchi Med Sch 2008; 55 (3–4): 35-42
    PubMedGoogle Scholar
  • 12 Salluh JI, Soares M, Teles JM. et al; Delirium Epidemiology in Critical Care Study Group. Delirium epidemiology in critical care (DECCA): an international study. Crit Care 2010; 14 (06) R210
    CrossrefPubMedGoogle Scholar
  • 13 Traube C, Silver G, Reeder RW. et al. Delirium in critically ill children: an international point prevalence study. Crit Care Med 2017; 45 (04) 584-590
    CrossrefPubMedGoogle Scholar
  • 14 Traube C, Silver G, Gerber LM. et al. Delirium and mortality in critically ill children: epidemiology and outcomes of pediatric delirium. Crit Care Med 2017; 45 (05) 891-898
    CrossrefPubMedGoogle Scholar
  • 15 Mehta S, Cook D, Devlin JW. et al; SLEAP Investigators; Canadian Critical Care Trials Group. Prevalence, risk factors, and outcomes of delirium in mechanically ventilated adults. Crit Care Med 2015; 43 (03) 557-566
    CrossrefPubMedGoogle Scholar
  • 16 Smith HAB, Gangopadhyay M, Goben CM. et al. Delirium and benzodiazepines associated with prolonged ICU stay in critically ill infants and young children. Crit Care Med 2017; 45 (09) 1427-1435
    CrossrefPubMedGoogle Scholar
  • 17 Carnahan RM, Lund BC, Perry PJ, Pollock BG, Culp KR. The anticholinergic drug scale as a measure of drug-related anticholinergic burden: associations with serum anticholinergic activity. J Clin Pharmacol 2006; 46 (12) 1481-1486
    CrossrefPubMedGoogle Scholar
  • 18 Madden K, Hussain K, Tasker RC. Anticholinergic medication burden in pediatric prolonged critical illness: a potentially modifiable risk factor for delirium. Pediatr Crit Care Med 2018; 19 (10) 917-924
    CrossrefPubMedGoogle Scholar
  • 19 Goldstein B, Giroir B, Randolph A. International Consensus Conference on Pediatric Sepsis. International pediatric sepsis consensus conference: definitions for sepsis and organ dysfunction in pediatrics. Pediatr Crit Care Med 2005; 6 (01) 2-8
    CrossrefPubMedGoogle Scholar
  • 20 Pollack MM, Patel KM, Ruttimann UE. PRISM III: an updated Pediatric Risk of Mortality score. Crit Care Med 1996; 24 (05) 743-752
    CrossrefPubMedGoogle Scholar
  • 21 Bangalore H, Gaies M, Ocampo EC. et al. The Total Inotrope Exposure Score: an extension of the Vasoactive Inotrope Score as a predictor of adverse outcomes after paediatric cardiac surgery. Cardiol Young 2017; 27 (06) 1146-1152
    CrossrefPubMedGoogle Scholar
  • 22 Franck LS, Scoppettuolo LA, Wypij D, Curley MA. Validity and generalizability of the Withdrawal Assessment Tool-1 (WAT-1) for monitoring iatrogenic withdrawal syndrome in pediatric patients. Pain 2012; 153 (01) 142-148
    CrossrefPubMedGoogle Scholar
  • 23 Curley MA, Harris SK, Fraser KA, Johnson RA, Arnold JH. State Behavioral Scale: a sedation assessment instrument for infants and young children supported on mechanical ventilation. Pediatr Crit Care Med 2006; 7 (02) 107-114
    CrossrefPubMedGoogle Scholar
  • 24 Traube C, Silver G, Kearney J. et al. Cornell Assessment of Pediatric Delirium: a valid, rapid, observational tool for screening delirium in the PICU*. Crit Care Med 2014; 42 (03) 656-663
    CrossrefPubMedGoogle Scholar
  • 25 Davis AL, Carcillo JA, Aneja RK. et al. American College of Critical Care Medicine clinical practice parameters for hemodynamic support of pediatric and neonatal septic shock. Crit Care Med 2017; 45 (06) 1061-1093
    CrossrefPubMedGoogle Scholar
  • 26 Kaur J, Singhi P, Singhi S, Malhi P, Saini AG. Neurodevelopmental and behavioral outcomes in children with sepsis-associated encephalopathy admitted to pediatric intensive care unit: a prospective case control study. J Child Neurol 2016; 31 (06) 683-690
    CrossrefPubMedGoogle Scholar
  • 27 Daoud A, Duff JP, Joffe AR. Alberta Sepsis Network. Diagnostic accuracy of delirium diagnosis in pediatric intensive care: a systematic review. Crit Care 2014; 18 (05) 489
    CrossrefPubMedGoogle Scholar
  • 28 Wolters AE, Zaal IJ, Veldhuijzen DS. et al. Anticholinergic medication use and transition to delirium in critically ill patients: a prospective cohort study. Crit Care Med 2015; 43 (09) 1846-1852
    CrossrefPubMedGoogle Scholar
  • 29 Mody K, Kaur S, Mauer EA. et al. Benzodiazepines and development of delirium in critically ill children: estimating the causal effect. Crit Care Med 2018; 46 (09) 1486-1491
    CrossrefPubMedGoogle Scholar
  • 30 Sullins AK, Abdel-Rahman SM. Pharmacokinetics of antibacterial agents in the CSF of children and adolescents. Paediatr Drugs 2013; 15 (02) 93-117
    CrossrefPubMedGoogle Scholar