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Should we Consider Nicotine Replacement Therapy (NRT) for Our Smoker Critically Ill Patients?

Nicotine Replacement Therapy (NRT) for Smoker Critically Ill Patients

Tobacco use is a significant cause of preventable deaths worldwide, and many patients in intensive care units (ICUs) are active smokers. These patients tend to exhibit agitation and often need larger doses of sedatives and analgesics [1]. While nicotine withdrawal might be a factor in this agitation, the link between tobacco use and ICU delirium isn't yet fully understood [2]. Although nicotine replacement therapy (NRT) has proven effective in easing withdrawal symptoms in those who quit smoking, its effectiveness and safety in critically ill patients remain questionable. Yet, NRT is frequently used in ICUs to manage withdrawal symptoms and agitation in smokers [3]. Despite its widespread use, the evidence around NRT's efficacy and safety in critical patients is conflicting. In this post, we will delve into the evidence for and against NRT usage in the ICU.

Do you prescribe NRT for your smoker ICU patients?

  • Yes

  • No

  • In certain cases, please explain in comment section

Observational Studies

Five observational studies examined the impact of nicotine replacement therapy (NRT) on patients in intensive care units (ICUs). A study by Lee et al. found that critically ill ICU patients who received NRT had higher hospital mortality rates and fewer ICU-free days [4]. Another study involving patients who had undergone coronary artery bypass graft (CABG) surgery reported a higher mortality rate among those who received NRT, particularly when off-pump CABG was performed [5].

On the other hand, another study found no significant difference in mortality rates between ICU patients who received NRT and those who did not. However, it failed to find any clear clinical benefit of NRT use in this setting [6]. A retrospective cohort study also concluded that there was no significant difference in ICU and hospital mortality rates between the NRT and non-NRT groups, suggesting no apparent harm from using NRT in the ICU [7].

Lastly, a case-control study indicated potential adverse effects associated with NRT use in the ICU, including a higher prescription rate of antipsychotic medication, increased use of physical restraints, and prolonged duration of mechanical ventilation [8].

While NRT is widely used to manage nicotine withdrawal in critically ill patients, it's essential to ensure that its benefits outweigh its potential risks. The insight gleaned from these studies suggests that NRT does not significantly reduce mortality rates among ICU patients. Some studies even suggest potential harm associated with its use, highlighting the need for careful evaluation and patient-specific decision-making when considering NRT. The results also underscore the importance of more comprehensive, randomized controlled trials to better understand the risks and benefits of NRT use in ICUs.

Randomized Control Trials in NRT

These two studies investigated the effects of nicotine replacement therapy (NRT) on ICU patients known to be smokers. The first study, a randomized trial with 40 patients, compared outcomes between a group receiving a 21 mg nicotine patch and a group receiving a placebo. The findings suggested a trend towards a reduction in ICU stay length and ventilator days in the NRT group, although these reductions were not statistically significant. Interestingly, the NRT group had a shorter duration of sedation/analgesia use, which could indicate a potential benefit of NRT in managing discomfort and stress in ICU patients [9].

The second study was a randomized, controlled, double-blind pilot study with 47 mechanically ventilated smokers. It aimed to assess the safety and efficacy of NRT. The study found no significant differences in the 30-day and 90-day mortality rates or the number of serious adverse events between the NRT and placebo groups. However, an interesting observation was that patients in the NRT group had a longer duration without delirium, sedation, and coma at day 20, and more of these patients were discharged from the ICU or hospital by day 30 [10].

Although neither study found that NRT significantly affected mortality rates or the frequency of serious adverse events, both studies suggested potential benefits of NRT in specific areas. The first study indicated a possible reduction in sedation/analgesia use with NRT, potentially reducing the risk of over-sedation and related complications. The second study suggested NRT may improve patient outcomes, as evidenced by a longer duration without delirium, sedation, and coma, and an increased rate of discharge by day 30.

However, both studies had relatively small sample sizes, which may limit the conclusiveness of the findings. Further research, particularly large, well-designed randomized controlled trials, is needed to more definitively establish the risks and benefits of NRT in ICU settings. Additionally, the potential benefits suggested by these studies should be considered alongside the results of earlier studies that found possible risks associated with NRT in ICU patients, highlighting the complex and multifaceted nature of NRT use in these settings.

Systematic Reviews in NRT

Three systematic reviews aimed to evaluate the effects of nicotine replacement therapy (NRT) on critically ill patients in ICU settings.

The first review evaluated the impact of NRT on mortality and other outcomes in nicotine-dependent critically ill patients. This review, which included seven studies, concluded that NRT should not be routinely prescribed in ICU settings due to limited evidence of effectiveness and potential indications of increased toxicity. However, it suggests considering NRT's use in selected patients where benefits outweigh the risks [11].

The second systematic review and meta-analysis included eight studies, with a total of 2,636 participants, to assess the impact of NRT on delirium, mortality, and length of stay in the ICU. The analysis of observational studies revealed an association between NRT use and increased delirium incidence. However, there were no significant differences found in ICU mortality, hospital mortality, or ICU-free days on day 28. Due to insufficient high-quality data, the review concluded that it's currently not recommendable to use NRT to prevent delirium or reduce mortality in critically ill smokers in the ICU [12].

The third review aimed to determine NRT's effect on agitation and delirium in ICU patients. Six studies were included in the review, and the findings were inconsistent. While some studies reported an association between NRT use and increased agitation or delirium, one study found no significant benefit or harm, and two studies reported a reduction in symptomatic nicotine withdrawal. Given the inconclusive evidence, the prescription of NRT should be evaluated on a case-by-case basis, considering the risk versus benefit [13].


The common theme from these studies and reviews is the lack of strong, high-quality evidence supporting the use of NRT in ICU patients. While some potential benefits are suggested, such as reduced symptomatic nicotine withdrawal, these reviews also highlight potential risks, including increased delirium incidence and possible toxicity. Therefore, the routine use of NRT in ICU settings is not currently recommended. Any decision to use NRT should be individualized, taking into consideration the potential risks and benefits for each patient. These conclusions underscore the need for more rigorous, well-designed studies to ascertain the safety and efficacy of NRT in this population.


  1. Lucidarme O, Seguin A, Daubin C, et al. Nicotine withdrawal and agitation in ventilated critically ill patients. Crit Care. 2010;14(2):R58

  2. Zaal IJ, Devlin JW, Peelen LM, et al. A systematic review of risk factors for delirium in the ICU. Crit Care Med. 2015;43(1):40–7

  3. Kowalski M, Udy AA, McRobbie HJ, et al. Nicotine replacement therapy for agitation and delirium management in the intensive care unit: a systematic review of the literature. J Intensive Care. 2016;15(4):69

  4. Lee AH, Afessa B (2007) The association of nicotine replacement therapy with mortality in a medical intensive care unit. Crit Care Med 35:1517–1521. Link

  5. Paciullo CA, Short MR, Steinke DT, Jennings HR (2009) Impact of nicotine replacement therapy on postoperative mortality following coronary artery bypass graft surgery. Ann Pharmacother 43:1197–1202. Link

  6. Cartin-Ceba R, Warner DO, Hays JT, Afessa B. Nicotine replacement therapy in critically ill patients: a prospective observational cohort study. Crit Care Med. 2011 Jul;39(7):1635-40. doi: 10.1097/CCM.0b013e31821867b8. PMID: 21494111. Link

  7. Gillies MA, McKenzie CA, Whiteley C, Beale RJ, Tibby SM. Safety of nicotine replacement therapy in critically ill smokers: a retrospective cohort study. Intensive Care Med. 2012 Oct;38(10):1683-8. doi: 10.1007/s00134-012-2604-2. Epub 2012 May 23. PMID: 22618096. Link

  8. Kerr A, McVey JT, Wood AM, Van Haren F. Safety of nicotine replacement therapy in critically ill smokers: a retrospective cohort study. Anaesth Intensive Care. 2016 Nov;44(6):758-761. doi: 10.1177/0310057X1604400621. PMID: 27832565. Link

  9. Pathak V, Rendon IS, Lupu R, Tactuk N, Olutade T, Durham C, et al. Outcome of nicotine replacement therapy in patients admitted to ICU: A randomized controlled double-blind prospective pilot study. Respir Care 2013;58:1625-9. Link

  10. de Jong, B., Schuppers, A.S., Kruisdijk-Gerritsen, A. et al. The safety and efficacy of nicotine replacement therapy in the intensive care unit: a randomised controlled pilot study. Ann. Intensive Care 8, 70 (2018). Link

  11. Wilby KJ, Harder CK. Nicotine replacement therapy in the intensive care unit: a systematic review. J Intensive Care Med. 2014 Jan-Feb;29(1):22-30. doi: 10.1177/0885066612442053. Epub 2012 Apr 17. PMID: 22513249. Link

  12. Ng KT, Gillies M, Griffith DM. Effect of nicotine replacement therapy on mortality, delirium, and duration of therapy in critically ill smokers: a systematic review and meta-analysis. Anaesth Intensive Care. 2017 Sep;45(5):556-561. doi: 10.1177/0310057X1704500505. PMID: 28911284. Link

  13. Kowalski M, Udy AA, McRobbie HJ, Dooley MJ. Nicotine replacement therapy for agitation and delirium management in the intensive care unit: a systematic review of the literature. J Intensive Care. 2016 Nov 15;4:69. doi: 10.1186/s40560-016-0184-x. PMID: 27891229; PMCID: PMC5109763. Link

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