Nicotine replacement therapy for agitation and delirium management in the intensive care unit: a systematic review of the literature.
ABSTRACT: Active smokers are prevalent within the intensive care setting and place a significant burden on healthcare systems. Nicotine withdrawal due to forced abstinence on admission may contribute to increased agitation and delirium in this patient group. The aim of this systematic review was to determine whether management of nicotine withdrawal, with nicotine replacement therapy (NRT), reduces agitation and delirium in critically ill patients admitted to the intensive care unit (ICU).The following sources were used in this review: MEDLINE, EMBASE, and CINAHL Plus databases. Included studies reported delirium or agitation outcomes in current smokers, where NRT was used as management of nicotine withdrawal, in the intensive care setting. Studies were included regardless of design or number of participants. Data were extracted on ICU classification; study design; population baseline characteristics; allocation and dose of NRT; agitation and delirium assessment methods; and the frequency of agitation, delirium, and psychotropic medication use.Six studies were included. NRT was mostly prescribed for smokers with heavier smoking histories. Three studies reported an association between increased agitation or delirium and NRT use; one study could not find any significant benefit or harm from NRT use; and two described a reduction of symptomatic nicotine withdrawal. A lack of consistent and validated assessment measures, combined with limitations in the quality of reported data, contribute to conflicting results.Current evidence for the use of NRT in agitation and delirium management in the ICU is inconclusive. An evaluation of risk versus benefit on an individual patient basis should be considered when prescribing NRT. Further studies that consider prognostic balance, adjust for confounders, and employ validated assessment tools are urgently needed.
Project description:INTRODUCTION: Smoking is highly addictive, and nicotine abstinence is associated with withdrawal syndrome in hospitalized patients. In this study, we aimed to evaluate the impact of sudden nicotine abstinence on the development of agitation and delirium, and on morbidities and outcomes in critically ill patients who required respiratory support, either noninvasive ventilation or intubation, and mechanical ventilation. METHODS: We conducted a prospective, observational study in two intensive care units (ICUs). The 144 consecutive patients admitted to ICUs and requiring mechanical ventilation for >48 hours were included. Smoking status was assessed at ICU admission by using the Fagerström Test of Nicotine Dependence (FTND). Agitation, with the Sedation-Agitation Scale (SAS), and delirium, with the Intensive Care Delirium Screening Checklist (ICDSC), were tested twice daily during the ICU stay. Agitation and delirium were defined by SAS >4 and ICDSC >4, respectively. Nosocomial complications and outcomes were evaluated. RESULTS: Smokers (n = 44) were younger and more frequently male and were more likely to have a history of alcoholism and to have septic shock as the reason for ICU admission than were nonsmokers. The incidence of agitation, but not delirium, increased significantly in the smoker group (64% versus 32%; P = 0.0005). Nicotine abstinence was associated with higher incidences of self-removal of tubes and catheters, and with more interventions, including the need for supplemental sedatives, analgesics, neuroleptics, and physical restraints. Sedation-free days, ventilator-free days, length of stay, and mortality in ICUs did not differ between groups. Multivariate analysis identified active smoking (OR, 3.13; 95% CI, 1.45-6.74; P = 0.003) as an independent risk factor for agitation. Based on a subgroup of 56 patients, analysis of 28 pairs of patients (smokers and nonsmokers in a 1:1 ratio) matched for age, gender, and alcoholism status found similar results regarding the role of nicotine withdrawal in increasing the risk of agitation during an ICU stay. CONCLUSIONS: Nicotine withdrawal was associated with agitation and higher morbidities in critically ill patients. These results suggest the need to look specifically at those patients with tobacco dependency by using the FTND in ICU settings. Identifying patients at risk of behavioral disorders may lead to earlier interventions in routine clinical practice.
Project description:BACKGROUND:Studies 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. RESULTS:We 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). CONCLUSIONS:NRT 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 2011.
Project description:This investigation examined predictors of utilization of nicotine replacement therapy (NRT) during a smoke-free psychiatric hospitalization.Smokers (N=324) were recruited from smoke-free adult inpatient psychiatric units. Exploratory analyses examined correlates of NRT provision and utilization.The prevalence of NRT use was 51% overall and was greater among patients offered NRT on admission (58%) versus later (34%), among patients with more severe depression and nicotine withdrawal, and among those who reported perceptions that NRT decreases nicotine withdrawal, provides a nicotine substitute, and helps with quitting smoking (p<.05, all comparisons). Although the ratio of nicotine patch dose to usual cigarettes per day was 1.2±.7, the ratio was negatively correlated with time to first cigarette (Spearman's ?=-.30, p<.01), suggesting potential underdosing of more dependent smokers.During smoke-free psychiatric hospitalizations, clinical management of nicotine withdrawal may be enhanced by offering patients NRT directly on admission, educating patients on the benefits of NRT, and increasing the dosage for more dependent smokers.
Project description:Trauma ICU patients may require high and/or prolonged doses of opioids and/or benzodiazepines as part of their treatment. These medications may contribute to drug physical dependence, a response manifested by withdrawal syndrome. We aimed to identify risk factors, symptoms, and clinical variables associated with probable withdrawal syndrome. Design:Prospective exploratory observational study. Setting:Trauma ICU in large medical center in Puerto Rico. Participants:Fifty patients who received opioids and/or benzodiazepines for greater than or equal to 5 days. Measurements and Main Results:Using an opioid/benzodiazepine withdrawal syndrome checklist developed from research in adult ICU patients, the Diagnostic and Statistical Manual of Mental Disorders-5, and the International Classification of Diseases, 10th Edition, we evaluated patients at baseline and for 72 hours after drug weaning was initiated. Patients received opioid/benzodiazepine (88%), opioid (10%), or benzodiazepine (2%). Probable withdrawal syndrome occurred in 44%, questionable withdrawal syndrome in 20%, and no withdrawal syndrome in 18 (36%). Signs that were more frequent in the probable withdrawal syndrome group were agitation, diarrhea, fever, tachypnea, lacrimation, and hyperactive delirium. Patients who developed probable withdrawal syndrome spent almost double the amount of time receiving mechanical ventilation, and length of stay was higher in both ICU and hospital when compared with patients in the other two groups. Age, cumulative opioid dose amounts, and previous drug (opioid/benzodiazepine, cannabis, cocaine, or heroin) use were associated with odds of developing withdrawal syndrome. With the addition of Richmond Agitation-Sedation Scale and delirium to the multilevel analysis, older age no longer had its protective effect, whereas increase in Richmond Agitation-Sedation Scale scores, delirium presence, and increased duration of mechanical ventilation were associated with higher odds of withdrawal syndrome. Conclusions:We identified probable withdrawal syndrome in a sample of trauma ICU patients through observation of several associated symptoms. Significant factors associated with withdrawal syndrome found in this study should be considered when caring for patients being weaned from opioids and/or benzodiazepines. Further validation of the opioid/benzodiazepine withdrawal syndrome checklist is recommended.
Project description:To compare the efficacy and safety of scheduled low-dose haloperidol versus placebo for the prevention of delirium (Intensive Care Delirium Screening Checklist ? 4) administered to critically ill adults with subsyndromal delirium (Intensive Care Delirium Screening Checklist = 1-3).Randomized, double-blind, placebo-controlled trial.Three 10-bed ICUs (two medical and one surgical) at an academic medical center in the United States.Sixty-eight mechanically ventilated patients with subsyndromal delirium without complicating neurologic conditions, cardiac surgery, or requiring deep sedation.Patients were randomly assigned to receive IV haloperidol 1 mg or placebo every 6 hours until delirium occurred (Intensive Care Delirium Screening Checklist ? 4 with psychiatric confirmation), 10 days of therapy had elapsed, or ICU discharge.Baseline characteristics were similar between the haloperidol (n = 34) and placebo (n = 34) groups. A similar number of patients given haloperidol (12/34 [35%]) and placebo (8/34 [23%]) developed delirium (p = 0.29). Haloperidol use reduced the hours per study day spent agitated (Sedation Agitation Scale ? 5) (p = 0.008), but it did not influence the proportion of 12-hour ICU shifts patients spent alive without coma (Sedation Agitation Scale ? 2) or delirium (p = 0.36), the time to first delirium occurrence (p = 0.22), nor delirium duration (p = 0.26). Days of mechanical ventilation (p = 0.80), ICU mortality (p = 0.55), and ICU patient disposition (p = 0.22) were similar in the two groups. The proportion of patients who developed corrected QT-interval prolongation (p = 0.16), extrapyramidal symptoms (p = 0.31), excessive sedation (p = 0.31), or new-onset hypotension (p = 1.0) that resulted in study drug discontinuation was comparable between the two groups.Low-dose scheduled haloperidol, initiated early in the ICU stay, does not prevent delirium and has little therapeutic advantage in mechanically ventilated, critically ill adults with subsyndromal delirium.
Project description:Delirium during intensive care unit (ICU) stay is frequent and associated with significant morbidity, mortality and healthcare-related costs. International guidelines suggest its prevention. However, curative treatment remains unclearly established. Despite contradictory and ambiguous academic literature, international guidelines suggest the use of second-generation (atypical) antipsychotics over haloperidol. However, haloperidol remains the most widely used neuroleptic worldwide as a first-line treatment of agitation and/or delirium. Dexmedetomidine, an alpha2-adrenergic receptors agonist, has shown its efficiency in the treatment of delirium in intubated patients but also in its prevention. Dexmedetomidine represents a widely used alternative to haloperidol. Only few studies have compared the efficacy of dexmedetomidine in non-intubated ICU patients as a first-line curative treatment of delirium. The main objective of the 4D trial is to demonstrate that dexmedetomidine decreases delirium duration compared to placebo.The 4D trial is an investigator-initiated, prospective, multicenter, randomized, double-blinded, two-arm trial, randomizing 300 non-intubated ICU patients with a diagnosis of agitated delirium to receive dexmedetomidine or placebo as a cure. In case of agitation (RASS??+?2), immediate haloperidol administration will be allowed, to protect patient and staff in charge, while waiting for study treatment action. The primary outcome measure is a composite of duration of agitation or delirium or the use of intubation with deep sedation and mechanical ventilation. Secondary outcomes include mortalities at 7 and 30 days, ICU length of stay and occurrence of adverse effects related to dexmedetomidine use (bradycardia or hypotension requesting any treatment; or haloperidol use (neuroleptic malignant syndrome, extrapyramidal syndrome, prolonged QTc). The sample size will allow the detection of a 50% decrease of agitation duration (120 min), of an absolute reduction of delirium duration (1 day) and of a 50% relative decrease of intubation and mechanical ventilation, with a type 1 error rate of 1.8% (error risk inflation due to components of composite) and power of 90%, assuming a 15% incidence of intubation and mechanical ventilation requirements, an agitation duration of 240 min and a delirium duration of 3 days. One hundred and ten patients by group will be needed. An intermediate analysis is scheduled and requires the inclusion of 150 patients.The 4D trial may provide important data on the safety of commonly used sedative dexmedetomidine and could have a significant impact on future treatment of non-intubated ICU patients presenting with agitated delirium.ClinicalTrials.gov , ID: NCT 03317067 . Registered on 23 October 2017.
Project description:OBJECTIVE:Benzodiazepines and anticholinergics are risk factors for delirium in the intensive care unit (ICU). We tested the impact of a deprescribing intervention on short-term delirium outcomes. DESIGN:Multisite randomized clinical trial. SETTING:ICUs of three large hospitals. PARTICIPANTS:Two hundred adults aged 18 years or older and admitted to an ICU with delirium, according to the Richmond Agitation-Sedation Scale and the Confusion Assessment Method for the ICU (CAM-ICU). Participants had a contraindication to haloperidol (seizure disorder or prolonged QT interval) or preference against haloperidol as a treatment for delirium, and were excluded for serious mental illness, stroke, pregnancy, or alcohol withdrawal. Participants were randomized to a deprescribing intervention or usual care. The intervention included electronic alerts combined with pharmacist support to deprescribe anticholinergics and benzodiazepines. MEASUREMENTS:Primary outcomes were delirium duration measured by the CAM-ICU and severity measured by the Delirium Rating Scale Revised-98 (DRS-R-98) and the CAM-ICU-7; secondary outcomes included adverse events and mortality. RESULTS:Participants had a mean age of 61.8 (SD = 14.3) years, 59% were female, and 52% were African American, with no significant differences in baseline characteristics between groups. No differences between groups were identified in the number exposed to anticholinergics (P = .219) or benzodiazepines (P = .566), the median total anticholinergic score (P = .282), or the median total benzodiazepine dose in lorazepam equivalents (P = .501). Neither median delirium/coma-free days (P = .361) nor median change in delirium severity scores (P = .582 for DRS-R-98; P = .333 for CAM-ICU-7) were different between groups. No differences in adverse events or mortality were identified. CONCLUSIONS:When added to state-of-the-art clinical services, this deprescribing intervention had no impact on medication use in ICU participants. Given the age of the population, results of clinical outcomes may not be easily extrapolated to older adults. Nonetheless, improved approaches for deprescribing or preventing anticholinergics and benzodiazepines should be developed to determine the impact on delirium outcomes. J Am Geriatr Soc 67:695-702, 2019.
Project description:Objectives:Delirium is a common acute cognitive impairment syndrome among intensive care unit (ICU) patients. This study was aimed to investigate the incidence, risk factors, and cumulative risk of delirium among ICU patients. Methods:A case-control study including clinical records of 452 patients were retrospectively analyzed. Delirium was assessed using the Confusion Assessment Method for the ICU and Richmond Agitation-Sedation Scale. Results:We found that 163 out of the 452 patients (36.1%) had delirium. Multivariate analysis showed that use of sedatives, length of ICU hospitalization, and physical restraint were independent risk factors for delirium. The additive effect of all three factors resulted to an odds ratio of 30.950. Conclusion:The incidence of delirium remained high. Thus, nurses shall strengthen the monitoring of delirium, regularly access the patient's level of calmness, and limit the use of physical restraint.
Project description:BACKGROUND:Pain and agitation are closely linked to the development of delirium, which affects 60%-87% of critically ill patients. Delirium is associated with increased mortality and morbidity. Clinical guidelines that suggest routine assessment, treatment and prevention of pain, agitation and delirium (PAD) is crucial to improving patient outcomes. However, the adoption of and adherence to PAD guidelines remain suboptimal, especially in community hospitals. The aim of this quality improvement study is to evaluate the impact of a multifaceted and multidisciplinary intervention on PAD management in a Canadian community intensive care unit (ICU). METHODS:This is a quality improvement, uncontrolled, before-and-after study of a multifaceted and multidisciplinary intervention targeting nurses (educational modules, visual reminders), family members (interviews, educational pamphlets and an educational video), physicians (multidisciplinary round script) and the multidisciplinary team as a whole (delirium poster). We will collect data every day for 6 weeks before implementing the intervention. Data collection will include clinical information and information on process of care. We will then implement the intervention. Four weeks after, we will collect data daily for 6 weeks to evaluate the effect of the intervention. On the basis of the volume of the ICU, we expect to enroll approximately 280 patients. We have obtained local ethics approval from the Hamilton Integrated Research Ethics Board (HiREB 18-040-C). INTERPRETATION:The results of this quality improvement study will provide information on adherence to PAD guidelines in a Canadian community ICU setting. They will also supply information on the feasibility of implementing multifaceted and multidisciplinary PAD interventions in community ICUs.
Project description:Electronic cigarettes (ECs) and nicotine replacement therapy (NRT) are non-combustible nicotine delivery devices being widely used as a partial or a complete long-term substitute for smoking. Little is known about the characteristics of long-term users, their smoking behaviour, attachment to smoking, experience of nicotine withdrawal symptoms, or their views on these devices. This study aimed to provide preliminary evidence on this and compare users of the different products.UK participants were recruited from four naturally occurring groups of long-term (?6 months) users of either EC or NRT who had stopped or continued to smoke (N=36 per group, total N=144). Participants completed a questionnaire assessing socio-demographic and smoking characteristics, nicotine withdrawal symptoms, smoker identity and attitudes towards the products they were using.Adjusting for relevant confounders, EC use was associated with a stronger smoker identity (Wald X(2)(1)=3.9, p=0.048) and greater product endorsement (Wald X(2)(1)=4.6, p=0.024) than NRT use, irrespective of smoking status. Among ex-smokers, EC users reported less severe mood and physical symptoms (Wald X(2)(1)=6.1, p=0.014) and cravings (Wald X(2)(1)=8.5, p=0.003), higher perceived helpfulness of the product (Wald X(2)(1)=4.8, p=0.028) and lower intentions to stop using the product (Wald X(2)(1)=17.6, p<0.001) than NRT users.Compared with people who use NRT for at least 6 months, those who use EC over that time period appear to have a stronger smoker identity and like their products more. Among long-term users who have stopped smoking, ECs are perceived as more helpful than NRT, appear more effective in controlling withdrawal symptoms and continued use may be more likely.