The safety and efficacy of nicotine replacement therapy in the intensive care unit: a randomised controlled pilot study

Abstract

BackgroundStudies evaluating nicotine replacement therapy (NRT) to prevent nicotine withdrawal symptoms in ICU patients have yielded conflicting results. We performed a randomised controlled double-blind pilot study to assess the safety and efficacy of NRT in critically ill patients. Mechanically ventilated patients admitted to two medical–surgical intensive care units and smoking more than 10 cigarettes per day before ICU admission were enrolled in this study. Participants were randomised to transdermal NRT (14 or 21 mg per day) or placebo until ICU discharge or day 30. Smoking status was confirmed by the biomarkers serum cotinine and urinary NNAL. The primary endpoint was 30-day mortality. Among secondary endpoints and post hoc endpoints, 90-day mortality, safety, time spent without delirium, sedation and coma, and patient destination at day 30 were addressed.ResultsWe enrolled 47 patients. No differences were found between NRT and control group patients concerning 30-day mortality (9.5 vs. 7.7%, p = 0.84) and 90-day mortality (14.3 vs. 19.2%, p = 0.67). The number of serious adverse events was comparable between groups (NRT: 4, control: 11, p = 0.13). At day 20, average time alive without delirium, sedation and coma was 16.6 days among NRT patients versus 12.6 days among control patients (p = 0.03). At day 30, more NRT group patients were discharged from the ICU or hospital compared with controls (p = 0.03).ConclusionsNRT did not affect mortality or the number of (serious) adverse events compared with placebo. Time alive without delirium, sedation and coma at day 20 in NRT patients was longer than in control patients. An adequately powered randomised controlled trial to further study safety and efficacy of NRT in ICU patients seems feasible and is warranted.Trial registration ClinicalTrials.gov, number NCT01362959, registered 1 June 2011Electronic supplementary materialThe online version of this article (10.1186/s13613-018-0399-1) contains supplementary material, which is available to authorized users.

Assessment of the sedative effects of dexmedetomidine and propofol treatment in patients undergoing mechanical ventilation in the ICU and relationship between treatment and occurrence of ventilator‑associated pneumonia and detection of pathogenic bacteria

“…Tracheal intubation primarily consists of mechanical ventilation, to which many patients develop intolerance (1,2). Sedative and analgesic adjuvant therapy is often required during clinical treatment, which reduces the discomfort and stress responses of patients and increases the effectiveness of mechanical ventilation (3). Moreover, studies have shown that appropriate sedation can improve the clinical outcomes of patients (4).…”

Pharmacological and non-pharmacological interventions to prevent delirium in critically ill patients: a systematic review and network meta-analysis

“…1 ), with a total of 17,140 participants [ 34 – 113 ]. Included trials were comprised of 54 (67.5%) pharmacological or sedation intervention studies [ 34 – 36 , 38 – 40 , 42 – 45 , 47 , 49 – 51 , 55 – 57 , 59 – 63 , 67 – 69 , 71 , 73 – 76 , 78 , 79 , 81 , 82 , 85 – 87 , 89 , 90 , 92 – 94 , 97 – 100 , 102 , 103 , 105 – 108 , 110 , 112 , 113 ] with 14,224 participants, 25 (31.3%) studies of non-pharmacological single or multi-component interventions with 2904 participants [ 37 , 41 , 46 , 48 , 52 , 53 , 57 , 58 , 64 – 66 , 70 , 72 , 77 , 80 , 83 , 84 , 88 , 91 , 95 , 96 , 101 , 104 , 109 , 111 ], and 1 study (1.2%) included a combination non-pharmacological with a pharmacological intervention with 12 participants [ 54 ]. Key features of all included trials are presented in detail in eTable 2.…”

“…Adverse events identified included device removal [ 34 , 36 , 44 , 47 , 56 , 76 , 81 , 85 , 95 , 98 , 106 ], reintubation [ 44 , 56 , 76 , 81 , 86 , 97 , 106 ], arrhythmias [ 35 , 67 , 89 , 97 , 99 , 107 , 113 ], tracheostomy [ 44 , 56 , 76 , 81 , 106 ], and extrapyramidal side effects [ 36 , 40 , 59 , 113 ]. Except for arrhythmias, we identified insufficient data to conduct pairwise comparisons or form a network.…”

“…Pairwise comparisons for environmental or multi-component interventions found no differences compared to standard care, with wide CIs (0.83, 95% CI 0.49-1.41 and 0.65, 95% CI 0.40-1.05, respectively) (eFigure 1). Adverse events identified included device removal [34,36,44,47,56,76,81,85,95,98,106], reintubation [44,56,76,81,86,97,106], arrhythmias [35,67,89,97,99,107,113], tracheostomy [44,56,76,81,106], and extrapyramidal side effects [36,40,59,113]. Except for arrhythmias, we identified insufficient data to conduct pairwise comparisons or form a network.…”

Nicotine patches in patients on mechanical ventilation for severe COVID-19: a randomized, double-blind, placebo-controlled, multicentre trial

“…Although it may be speculated that an acute deprivation of nicotine in smokers may be associated with worse outcomes in COVID-19 patients (for example, due to an acute upregulation of ACE2 and increased secretion of proinflammatory cytokines) that may be reversed by nicotine replacement therapy, including current smokers may have introduced a major bias in the interpretation of the impact of nicotine in severe COVID-19. Additionally, nicotine replacement therapy is sometimes recommended in ICU patients to prevent withdrawal syndrome [ 44 ]. Fourth, we cannot exclude a preventive effect of nicotine, if administered earlier, on contamination by SARS-CoV-2 or on the progression to severe forms of the disease.…”