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. This retrospective, matched cohort study observed 252 patients and suggested that there maybe harm associated with NRT, leading to agitation and prolonged mechanical ventilation.

Two small pilot RCT's, the first, 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. The second, ICU NRT RCT randomized 48 patients and found no difference in 30 day mortality but found a decrease in duration of delirium.

A large, prospective RCT is needed to answer the question.


As of February 2019, no guidelines have been published that reflect the results of this trial.


  • Single Centre, retrospective, observational, matched case-control trial
  • N=252
    • Nicotine Replacement Therapy (NRT) (n=126)
    • no-NRT (n=126)
  • Setting: 31-bed mixed medical/surgical tertiary referral ICU in Australia
  • Enrollment: 2009-2014
  • Primary Outcome: Proportion of patients who received antipsychotic medications in ICU


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, dose not reported


Comparisons are NRT group vs. Control Group

Primary Outcomes

Antipsychotic administration
34% vs. 11%, P < 0.01

Secondary Outcomes

Physical Restraints used
29% vs. 9.5%, P < 0.01
30-day Mortality
7.1% vs. 9.5%, P = 0.49
Mechanical Ventilation Requirements
56% vs. 55%, P = 0.81
Duration of Intubation, Days(IQR)
2.56(1.8-3.3) vs. 1.44(0.97-1.9), P = 0.012
Dexmedetomidine use
1.6% vs. 0.8%, P = 0.34


  • 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