|Year : 2019 | Volume
| Issue : 1 | Page : 38-42
Management of heavy smokers in the intensive care unit
Department of Pharmaceutical Care, Ministry of the National Guard Health Affairs; Department of Pharmacy Practice, College of Pharmacy, King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia
|Date of Web Publication||30-May-2019|
Department of Pharmaceutical Care, Ministry of the National Guard Health Affairs, Riyadh; College of Pharmacy, King Saud bin Abdulaziz University for Health Sciences, Riyadh
Source of Support: None, Conflict of Interest: None
Quitting smoking abruptly can precipitate the nicotine withdrawal syndrome, characterized by psychological and physical components. Data from critically ill patients have shown that active smokers are more likely to suffer from psychomotor agitation, self-removal of tubes and catheters, need for physical restraint, and therefore usually require higher doses of sedatives, neuroleptics, and analgesic agents. Furthermore, smokers admitted to the intensive care unit (ICU) experience delirium or agitation, which increases the length of hospital stay and the cost of medical care. Nicotine replacement therapy (NRT) has been shown to be safe and effective in the outpatient setting in smokers who intended to quit. However, the management of nicotine withdrawal symptoms in critically ill patients is controversial. Several studies have identified that treating nicotine withdrawal symptoms with NRT can be beneficial while others suggest that it can potentially increase mortality in critically ill patients. In the absence of high-quality data, NRT cannot currently be recommended for routine use to prevent delirium or to reduce hospital or ICU mortality in critically ill smokers. From the currently available data, it seems that the use of NRT in critically ill patients should be limited to selected patients where the potential benefit clearly outweighs the risk. To establish definitive conclusions regarding the use of NRT in smokers admitted to the ICU, it is necessary to carry out well-designed prospective studies with a sample of adequate size to limit the confounding factors and biases present in the current retrospective observational studies.
Keywords: Critical Care, ICU, nicotine, smoker
|How to cite this article:|
Grmaish J. Management of heavy smokers in the intensive care unit. Saudi Crit Care J 2019;3:38-42
| Introduction|| |
Smoking has become a major public health problem worldwide due to its high prevalence and the well-known mortality and morbidity associated with its use. According to data published by the World Health Organization on the global tobacco epidemic in 2017, it is estimated that the prevalence of adult smokers in Saudi Arabia is 12.2%. Approximately 25%–47% of patients admitted to the intensive care medicine (intensive care unit [ICU]) are active smokers as reported from several prospective studies., These studies reveal that critical care providers encounter current smokers at a higher rate than the general population.
The unexpected disruption of cigarette smoking and nicotine intake in hospitalized patients may contribute to additional morbidity by the development of nicotine withdrawal symptoms that may complicate patient recovery and prolong hospital stay., When smokers are admitted to ICUs, they must cope with the effects of enforced nicotine withdrawal. The effects of nicotine withdrawal in critically ill patients are not well understood. In addition, the management of nicotine withdrawal symptoms in this patient population is controversial.
In this chapter, we will review the available evidence of using nicotine replacement therapy (NRT) in the smoker patients admitted to the ICU. It must be stressed that the evidence of using such therapy in critically ill patients is of moderate to low quality. The main contributing factors to the paucity of high-quality evidence in this area include underrecognition of the condition by critical care providers and methodological limitations of the published studies (e.g., small sample size, nonrandomized, retrospective design, and confounding factors). By identifying ICU patients who experience nicotine withdrawal symptoms and in reviewing the role of NRT to treat these symptoms in this population, we hope to raise awareness about this potentially overlooked aspect of patient care within the ICU.
| Nicotine Withdrawal in the Intensive Care Unit|| |
Nicotine is one of the main components of tobacco smoke. Chronic exposure to this substance is capable of developing addiction in smokers through upregulation of nicotinic acetylcholine receptors (nAChR). The agonist effects of nicotine on nAChR induce the release of neurotransmitters such as acetylcholine, dopamine, and γ-aminobutyric acid. The effects of nicotine are systemic and cause neurological, respiratory, cardiovascular, immunological, and gastrointestinal sequelae.
Quitting smoking abruptly can precipitate the nicotine withdrawal syndrome, characterized by psychological and physical components. These include bradycardia, hypotension, constipation, sleep disorders, anxiety, irritability, agitation, anger, restlessness, desire, confusion, delirium, hallucinations, and mood disorders. Nicotine withdrawal symptoms usually reach their peak in the first 3 days of quitting and decline over the course of the next 3–4 weeks. Data from critically ill patients have shown that active smokers are more likely to suffer from psychomotor agitation, self-removal of tubes and catheters, need for physical restraint, and therefore usually require higher doses of sedatives, neuroleptics, and analgesic agents in comparison to nonsmoking patients. Furthermore, >50% of smokers admitted to the ICU experience delirium or agitation, which increases the length of hospital stay and the cost of medical care as a consequence of nicotine abstinence on their ICU admission.
| Nicotine Replacement Therapy|| |
The objective of NRT is to temporarily replace the nicotine in cigarettes and reduce the motivation to smoke and the symptoms of withdrawal syndrome, thus facilitating the transition from smoking to complete abstinence.
There are several commercial forms through which the NRT can be administered; the most commonly used are chewing gum, transdermal patch, nasal spray, inhaler, sublingual tablets, and lozenges. However, the transdermal route may be preferred in the ICU patients because of ease of use and consistency in nicotine delivery in this population. The available nicotine patches in the market deliver 7, 14, or 21 mg over 24 h.
NRT has been shown to be safe and effective in the outpatient setting in smokers who intended to quit. Studies of using NRT in this population showed no increased risk of stroke, arrhythmia, angina, myocardial infarction, or death., However, it remains unclear whether these conclusions can be extrapolated to critically ill patients.
| Use of Nicotine Replacement Therapy in Patients Admitted to the Intensive Care Unit|| |
Management of nicotine withdrawal symptoms in critically ill patients has not been well studied and is controversial because of the contradictory results of the published studies. Several studies have identified that treating nicotine withdrawal symptoms with NRT can be beneficial while others suggest that treatment can potentially increase mortality in intensive care patients.,,,,,, Below is an overview of various studies that addressed this issue [Table 1].
|Table 1: Summary of studies on nicotine replacement therapy in critically ill patients|
Click here to view
In a retrospective case–control study conducted in the US in 2007, 90 patients who were smokers at admission to the ICU and had received NRT were matched on 1:1 basis to ICU patients who were smokers but did not receive NRT and were of a similar age and acute physiology, age, and chronic health evaluation (APACHE) score. There were no statistical differences between groups in terms of diagnoses of admission and comorbidities. Noteworthy, the most common diagnosis in both groups was drug overdose (52%). Among those who were not admitted due to an overdose, a 49% (18/37) mortality rate was evidenced in the NRT group compared to 13% (6/48) in the control group (P = 0.0002). However, on adjusting for factors such as illness severity and the need of invasive ventilation, the results showed an odds ratio for mortality with NRT of 19.7. The study thereby concluded suggesting that NRT can increase the hospital mortalities in patients who are critically ill. There are certain elements that call into question the validity of this study by looking closely at the results. This includes the fact that the majority of deaths in the NRT group were not due to cardiac causes (which could be expected given the “cardiac toxicity” of nicotine), and there was no difference in cardiovascular support between both groups. In addition, the small sample size (only 37 patients in the NRT group and 48 patients in the control group) and the fact that the majority of the included patients had a short stay in the ICU made the reported mortality rates not convincing enough to accept the authors' conclusion.
Another retrospective cohort pilot study was conducted in 2009 where random transdermal NRT was prescribed to 67 smokers admitted to the ICU after coronary artery bypass graft surgery. Patients were matched in a 1:1 ratio with those who did not receive NRT. The results of this study showed a statistically nonsignificant increase in the mortality of the patients who received NRT in comparison to those who did not receive NRT (P = 0.080). Given the nature and method of this study, the authors accept that the study was small and concluded that it should be considered as a pilot study with a high negative probability of mortality.
Cartin-Ceba et al. evaluated 330 smokers admitted to a medical ICU of a tertiary academic hospital in a prospective study in which 174 patients received NRT and 156 did not receive NRT. There were no significant differences in mortality between the two groups; 14 patients (7.8%) died in the NRT group compared to 10 patients (6.3%) in the non-NRT group (P = 0.59). Even after adjusting the data for severity of illness and propensity score for administration of NRT on ICU admission, it was evident that NRT was not associated with an increase in hospital mortality (odds ratio, 1.4, 95% confidence interval, 0.5–3.9, P = 0.51). Of interest, NRT was associated with more days with a positive Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) (delirium assessment method for the ICU) score but a lower median Richmond Agitation-Sedation Scale score. Furthermore, higher cumulative doses of opioids and benzodiazepines were required in patients taking NRT, but less dexmedetomidine and haloperidol were required. While it is clear that this study showed that NRT is not associated with an increase in hospital mortality in critically ill patients, it did not demonstrate any clinically significant benefit from using NRT in the ICU setting.
A retrospective study of 423 smokers in a mixed medical and surgical ICU assessed the use of NRT by a group of Guy's and St Thomas' NHS Foundation Trust, of whom 73 patients received transdermal NRT. The unadjusted ICU and hospital mortality were lower for the group of NRT, although both differences were not statistically significant. In addition, after adjustment for APACHE score, age, and alcohol use, there were no statistical differences in both ICU and hospital mortality between the two groups (hazard ratio 0.50, [95% confidence interval (CI) 0.20–1.24], P = 0.14) and (hazard ratio 0.95, [95% CI 0.52–1.75], P = 0.88), respectively. The authors were unable to demonstrate any harm associated with NRT in this study and concluded that a randomized, blinded, placebo-controlled trial is required to assess adequately the safety and efficacy of NRT as a treatment in critically ill smokers.
In a small pilot study, 40 critically ill patients were randomly assigned to receive NRT (21 mg of nicotine per day) or placebo until ICU discharge. The average stay in the ICU was 4.5 days in the NRT group and 7 days in the control group (P = 0.08). The average number of days on the ventilator was 1.9 in the NRT group and 3.5 in the control group (P = 0.47). The number of days of sedation and analgesia was also lower in the NRT group than in the control group. However, all the reported results were not statically significant.
In a case–control study conducted in a mixed medical and surgical ICU in Australia over a period of 5 years, 126 active smokers who received transdermal NRT matched to 126 active smokers who did not receive NRT. The matched individuals had similar demographic characteristics and APACHE II scores. Antipsychotic medication was prescribed in 43 (34.1%) patients who received NRT compared to 14 (11.1%) in controls (P < 0.01). Physical restraints were used in 37 (29.4%) patients who received NRT, compared to 12 (9.5%) controls (P < 0.01). The 30-day mortality and number of patients intubated were not statistically different between groups. The average length of intubation time was greater in the NRT group (2.56 days) compared to the control group (1.44 days) (P = 0.012). These findings are very interesting but should be interpreted with caution since baseline imbalances could have contributed to the results observed. The groups were well matched by age, sex, the severity of the disease, and elective income versus emergency admission; however, there were substantial differences between the admissions diagnoses. In addition, the study did not assess smoking history or whether patients included in the study consumed alcohol or other psychoactive drugs before admission. It seems that the sample size in this study is appropriate, but the generalizability of the results is limited due to its single center and retrospective design.
Recently, a double-blind randomized controlled pilot study was published in 2018. The study was conducted to assess the safety and efficacy of NRT in 47 critically ill patients in medical-surgical ICU. Participants were randomized to receive transdermal NRT (14 or 21 mg per day) or placebo. No significant differences were found between the patients with NRT and the control group in terms of ICU mortality (9.5% NRT group vs. 7.7% control group, P = 0.84) and the 90-day mortality (14.3 vs. 19.2%, P = 0.67). The number of serious adverse events was similar in both groups (4 in NRT and 11 in control, P = 0.13). At day 20, the time of life without delirium, sedation, and/or coma was longer in patients with NRT (16.6 days) versus in control group (12.6 days) (P = 0.03). In this study, smoking status (minimum 10 cigarettes per day) was determined by a questionnaire and confirmed by serum cotinine tests or by the determination of urinary NNAL (4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanol; which is a metabolite of tobacco products). The exhaustive selection of patients with subsequent confirmation of the biomarker ensured the inclusion of active smokers and increased the validity of this study. However, the main limitation of the study is the size of the sample; therefore, definitive conclusions cannot be drawn only based on these results.
| Conclusions|| |
The majority of studies that evaluated the use of NRT in smokers who admitted to the ICU were observational in nature and subsequently subject to bias and confounding. In addition, many of these studies did not assess the use of alcohol and recreational drugs. It is possible that patients receiving NRT may also be at increased risk of withdrawal from alcohol and drugs leading to inaccurate results of many studies.
The main findings from the available studies showed no statistically significant increase in hospital mortality and ICU mortality in this patient population. The NRT is used in smokers admitted to an ICU with the objective of reducing the symptoms of nicotine withdrawal such as agitation and delirium; however, there is no strong evidence of significant reduction in these symptoms as described in the studies. Furthermore, no benefits were evidenced in the ICU stay or ventilation days.
In the absence of high-quality data, NRT cannot currently be recommended for routine use to prevent delirium or to reduce hospital or ICU mortality in critically ill smokers. While it is true for most of the controversial issues in the intensive care medicine, it seems to be the case for NRT that its use in critically ill patients should be limited to selected patients where the potential benefit clearly outweighs the risk. This might be applicable in selected smokers admitted to the ICU with delirium and sedation problems. To establish definitive conclusions regarding the safety and efficacy of the NRT in smokers admitted to the ICU, it is necessary to carry out well-designed prospective studies with a sample of adequate size to limit the confounding factors and biases present in retrospective observational studies.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Ezzati M, Lopez AD. Estimates of global mortality attributable to smoking in 2000. Lancet 2003;362:847-52.
Rimmer M. The global tobacco epidemic, the plain packaging of tobacco products, and the World Trade Organization. QUT Law Rev 2017;17:131-60.
Lucidarme O, Seguin A, Daubin C, Ramakers M, Terzi N, Beck P, et al.
Nicotine withdrawal and agitation in ventilated critically ill patients. Crit Care 2010;14:R58.
Møller AM, Pedersen T, Villebro N, Schnaberich A, Haas M, Tønnesen R. A study of the impact of long-term tobacco smoking on postoperative intensive care admission. Anaesthesia 2003;58:55-9.
Rigotti NA, Arnsten JH, McKool KM, Wood-Reid KM, Singer DE, Pasternak RC. The use of nicotine-replacement therapy by hospitalized smokers. Am J Prev Med 1999;17:255-9.
West R, Russell M. Cardiovascular and subjective effects of smoking before and after 24 h of abstinence from cigarettes. Psychopharmacology 1987;92:118-21.
Wilby KJ, Harder CK. Nicotine replacement therapy in the intensive care unit: A systematic review. J Intensive Care Med 2014;29:22-30.
Mitrouska I, Bouloukaki I, Siafakas N. Pharmacological approaches to smoking cessation. Pulm Pharmacol Ther 2007;20:220-32.
Cahill K, Stevens S, Perera R, Lancaster T. Pharmacological interventions for smoking cessation: An overview and network meta-analysis. Cochrane Database Syst Rev 2013;(5):CD009329.
Ely EW, Shintani A, Truman B, Speroff T, Gordon SM, Harrell FE Jr., et al.
Delirium as a predictor of mortality in mechanically ventilated patients in the intensive care unit. JAMA 2004;291:1753-62.
Lee AH, Afessa B. The association of nicotine replacement therapy with mortality in a medical intensive care unit. Crit Care Med 2007;35:1517-21.
Paciullo CA, Short MR, Steinke DT, Jennings HR. Impact of nicotine replacement therapy on postoperative mortality following coronary artery bypass graft surgery. Ann Pharmacother 2009;43:1197-202.
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;39:1635-40.
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;38:1683-8.
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.
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;44:758-61.
de Jong B, Schuppers AS, Kruisdijk-Gerritsen A, Arbouw ME, van den Oever HLA, van Zanten ARH, et al.
The safety and efficacy of nicotine replacement therapy in the intensive care unit: A randomised controlled pilot study. Ann Intensive Care 2018;8:70.