NRT in ICU Cohort

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Kerr A, McVey JT, Wood AM, Van Haren FMP. "Safety of nicotine replacement therapy in critically ill smokers: a retrospective cohort study". Anaesth Intensive Care. 2016. 44(6):758-761.
PubMedFull text

Clinical Question

In critically ill actively smoking patients, how does receiving nicotine replacement therapy (NRT) affect agitation, ventilator requirements, and mortality?

Bottom Line

In this small observation case-control cohort, receiving nicotine replacement therapy (NRT) increased agitation and prolonged mechanical ventilation; a large RCT is required to clarify if patients should receive NRT to replace empirically to prevent nicotine withdrawal syndrome.

Major Points

The use of nicotine replacement therapy (NRT) among smokers admitted to the ICU is controversial. A systematic review in 2014,[1] which included a majority of retrospective cohort studies, suggests that the risk of NRT may not outweigh the benefits. The authors go on to suggest an RCT would be required to answer the question, the very place this trial fits. The small pilot study, NRT in ICU Pilot randomized 40 ICU patients to NRT or placebo. It found a trend towards improved outcomes in terms of time in ICU, length of mechanical ventilation, and use of sedation and analgesia. This trial did not reach statistical significance nor did it assess/report adverse events. This retrospective cohort trial showed potential harm in these patients thus a large RCT is necessary to answer the clinical question. This larger RCT completed in August 2016 and is awaiting publication [2] which may better address this question.


To date no guidelines reflect the findings of this trial.


  • Single Centre, retrospective, observational, matched case-control trial
  • N=252
    • Nicotine Replacement Therapy (n=126)
    • no-NRT (n=126)
  • Setting: 31-bed mixed medical/surgical tertiary referral ICU
  • Enrollment: 2009-2014
  • Primary Outcome: administration of anti-psychotics


Inclusion Criteria

  • Active smokers

Exclusion Criteria

  • nil

Baseline Characteristics

NRT group shown

  • Age, years, mean (SD): 54(14.4)
  • APACHE II, mean (SD): 15.6(6.8)
  • Males, no. (%): 76(60)
  • ICU admission category, no. (%)
    • Elective admissions: 19(15)
    • Endocrine: 3(2)
    • Infectious disease: 14(11)
    • Respiratory: 31(24)
    • Renal: 3(2)
    • Cardiology: 11(8)
    • Neurology: 16(12)
    • Oncology: 1(1)
    • Gastroenterology: 13(10)
    • Vascular: 4(3)
    • Trauma: 20(16)
    • Other: 9(7)
    • Haematology: 1(1)


  • Transdermal Nicotine Replacement therapy


Comparisons are NRT group vs. Control Group, P-value

Primary Outcomes

Antipsychotic administration, %
34 vs. 11, <0.01

Secondary Outcomes

Physical Restraints, %
29 vs. 9.5, <0.01
30-day Mortality, %
7 vs. 9, NS
Mechanical Ventilation Requirements, %
56 vs. 55, NS
Duration of Intubation, Days(IQR)
2.6(1.8-3.3) vs. 1.4(0.97-1.9), 0.012


  • Observer bias - NRT may have been applied by the treating clinician due to current delirium in a bid to treat nicotine withdrawal induced delirium, not the opposite as may be inferred
    • Prescriber preference may also affect outcome
  • causation vs. correlation error possible with retrospective, observational nature of this paper
  • additional confounders possible without including previous smoking history, ethanol consumption, or other psychotropic drug use
  • Generalizability limited due to single centre, retrospective design


Not Stated

Further Reading

  1. Wilby KJ & Harder CK Nicotine replacement therapy in the intensive care unit: a systematic review. J Intensive Care Med 2014. 29:22-30.
  2. Nicotine Replacement Therapy in the Intensive Care Unit (NicGoWell) listing on