ICU NRT RCT

Incomplete

de Jong B. "The safety and efficacy of nicotine replacement therapy in the intensive care unit: a randomised controlled pilot study". Ann Intensive Care. 2018. 8(1):70.
PubMed • Full text • PDF

Clinical Question

In active smokers admitted to the ICU and requiring mechanical ventilation, what is the safety and efficacy of transdermal nicotine replacement as compared to placebo.

Bottom Line

Nicotine replacement therapy did not decrease mortality at 30 days but may have decreased duration of delirium and ICU length of stay.

Major Points

The use of nicotine replacement therapy (NRT) among smokers admitted to the ICU is controversial. A systematic review in 2014, 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. This small pilot study, 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. A systematic review in 2016 including 6 trials stated that use of NRT in agitation and delirium was inconclusive.

This pilot RCT randomized 48 patients in two Dutch mixed medical-surgical ICU's and found the use of NRT to provide no benefit in mortality, use of restraints, ICU and hospital length of stay, but found a decrease in the duration of delirium.

Another pilot RCT, 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 retrospective, matched cohort study NRT in ICU Cohort observed 252 patients and suggested that there maybe harm associated with NRT, leading to agitation and prolonged mechanical ventilation.

A larger, prospective RCT is needed.

Guidelines

As of June 2018, no guidelines have been published that reflect the results of this trial.

Design

• Multicenter, double-blind, randomized, controlled trial
• N=48
  • NRT (n=21)
    • 14mg patch (n=13)
    • 21mg patch (n=8)
  • Placebo (n=26)
• Setting: 2 university-affiliated teaching medical-surgical ICU’s in the Netherlands
• Enrollment: 2012-2016
• Follow-up: 30 days
• Primary Outcome: 30 day Mortality

Population

Inclusion Criteria

• Actively smoking
• Requiring mechanical ventilation

Exclusion Criteria

• age <18 years
• last smoking >72 h before inclusion
• smoking ≤10 cigarettes/day
• >48 h after hospital admission admitted to the ICU
• expected duration of mechanical ventilation ≤ 48 h
• pregnant or breastfeeding
• history of dementia or psychosis
• neurologic disease on admission such as traumatic brain injury, *intracranial haemorrhage
• seizures
• meningitis
• encephalitis
• intracranial tumour
• cerebrovascular accident
• NRT<2 weeks before ICU admission
• acute myocardial infarction
• severe cardiac arrhythmia
• unstable angina pectoris
• generalised skin diseases
• severe hearing deficiency
• hypersensibility to nicotine or patches
• insufficient Dutch language skills
• imminent death
• participation in another intervention study

Baseline Characteristics

BLANK Group displayed

• Demographics:
• Physiologic parameters:
• Anthropomorphics: Weight
• Labs:
• Site of infection

Interventions

• Transdermal Nicotine Replacement Therapy (NRT)
  • < 21 cigarettes/day received patches delivering 14 mg nicotine/24 h
  • ≥ 21 cigarettes/day received patches delivering 21 mg nicotine/24 h
• Placebo transdermal patch

Outcomes

Comparisons are NRT vs. Placebo.

Primary Outcomes

30 day mortality

9.5% vs. 7.7% (OR 0.96, 95% CI 0.11-8.23) P = 0.84

Secondary Outcomes

90 day mortality

14.3% vs. 19.2%, P = 0.67

ICU Length of stay

186 h vs. 246 h, P = 0.41

Hospital Length of stay

313 h vs. 408 h, P = 0.356

Hours without delirium

8 vs. 16, P = 0.152

Duration of physical restraint

12 h vs. 44.5 h, P = 0.417

Total doses of haloperidol

9mg vs. 19.5mg, P = 0.185

Subgroup Analysis

Alive without delirium, sedation, or coma

Day 10 - 160 h vs. 88 h, P = 0.04

Day 20 - difference 104 h for NRT, P = 0.03

Day 30 - difference 86 h for NRT, P = 0.077

Adverse Events

Total Adverse Events

37% vs. 63%, P = 0.096

Criticisms

• Excluded patients smoking less than 10 cigarettes/day
• Did not meet sample size of 70 participants
• External validity may be limited
• Small sample size may limit wider application without larger study

Funding

• Not Reported