title: Nicotine replacement therapy for agitation and delirium management in the intensive care unit: a systematic review of the literature.
abstract: BACKGROUND
  Active smokers are prevalent within the intensive care setting and place a significant burden on healthcare systems. Nicotine withdrawal due to forced abstinence on admission may contribute to increased agitation and delirium in this patient group. The aim of this systematic review was to determine whether management of nicotine withdrawal, with nicotine replacement therapy (NRT), reduces agitation and delirium in critically ill patients admitted to the intensive care unit (ICU).
  
  
  METHODS
  The following sources were used in this review: MEDLINE, EMBASE, and CINAHL Plus databases. Included studies reported delirium or agitation outcomes in current smokers, where NRT was used as management of nicotine withdrawal, in the intensive care setting. Studies were included regardless of design or number of participants. Data were extracted on ICU classification; study design; population baseline characteristics; allocation and dose of NRT; agitation and delirium assessment methods; and the frequency of agitation, delirium, and psychotropic medication use.
  
  
  RESULTS
  Six studies were included. NRT was mostly prescribed for smokers with heavier smoking histories. Three studies reported an association between increased agitation or delirium and NRT use; one study could not find any significant benefit or harm from NRT use; and two described a reduction of symptomatic nicotine withdrawal. A lack of consistent and validated assessment measures, combined with limitations in the quality of reported data, contribute to conflicting results.
  
  
  CONCLUSIONS
  Current evidence for the use of NRT in agitation and delirium management in the ICU is inconclusive. An evaluation of risk versus benefit on an individual patient basis should be considered when prescribing NRT. Further studies that consider prognostic balance, adjust for confounders, and employ validated assessment tools are urgently needed.
authors.affiliation: Pharmacy Department, Alfred Health, 55 Commercial Road, Melbourne, VIC 3004 Australia ; Intensive Care Unit, Alfred Health, Melbourne, Australia ; Monash University, Melbourne, Australia.
authors.forename: Melanie
authors.identifier: 0000-0002-7067-9114
authors.initials: M
authors.lastname: Kowalski
authors.affiliation: Intensive Care Unit, Alfred Health, Melbourne, Australia ; Monash University, Melbourne, Australia.
authors.forename: Andrew A
authors.initials: AA
authors.lastname: Udy
authors.affiliation: Wolfson Institute of Preventive Medicine, London, UK ; Queen Mary University of London, London, UK.
authors.forename: Hayden J
authors.initials: HJ
authors.lastname: McRobbie
authors.affiliation: Pharmacy Department, Alfred Health, 55 Commercial Road, Melbourne, VIC 3004 Australia ; Monash University, Melbourne, Australia.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Dooley
keywords: Agitation; Critical care; Delirium; Intensive care unit; Nicotine replacement therapy; Nicotine withdrawal