CoChat
Sign Up
Cited by 85Intensive Care Unit Cognitive DisordersSmoking Behavior and CessationAnesthesia and Sedative Agents

Nicotine withdrawal and agitation in ventilated critically ill patients

Open access
Lucidarme, Olivier, Seguin, Amélie, Daubin, Cédric, Ramakers, Michel, Terzi, Nicolas, Beck, Patrice, Charbonneau, Pierre, du Cheyron, Damien·2010·Critical Care
DOI 10.1186/cc8954PMC PMC2887179
Open this paper in CoChat — free accountOpen PDF

Abstract

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.

AI snapshot

Written from the paper’s full text.

TL;DR

In a prospective observational study of 144 mechanically ventilated ICU patients, active smoking/nicotine withdrawal was associated with agitation but not delirium, and with more adverse events such as self-removal of tubes and catheters. Active smoking remained an independent risk factor for agitation (OR, 3.13; 95% CI, 1.45–6.74; P = 0.003), while ICU mortality, length of stay, sedation-free days, and ventilator-free days did not differ between groups.

Key findings

  • Agitation occurred in 64% of smokers versus 32% of nonsmokers (P = 0.0005), whereas delirium occurred in 37% versus 24% (P = 0.2).
  • Active smoking was independently associated with agitation in multivariate analysis (OR, 3.13; 95% CI, 1.45–6.74; P = 0.003); in a matched case-control subgroup, agitation was 80% in smokers versus 42% in nonsmokers (RR, 1.9; 95% CI, 1.3–3.0; P = 0.004).
  • Smokers had higher rates of accidental removal of endotracheal tubes (7.5 vs 3.7; P < 0.0001), arterial/venous/bladder catheters (20.1 vs 11.9; P < 0.0001), and nasogastric tubes (33.5 vs 22.4; P = 0.0003), as well as more supplemental sedatives/analgesics (52% vs 15%; P < 0.0001), physical restraints (48% vs 13%; P < 0.0001), and neuroleptics (25% vs 7%; P = 0.005).
  • No differences were found between smokers and nonsmokers in nosocomial infections, sedation-free days, ventilator-free days, ICU length of stay, or ICU mortality.

Methods

  • Prospective observational study conducted from June 2007 to April 2008 in two adult ICUs in Normandy, France; 916 admissions were screened, 150 met inclusion criteria, 6 were secondarily excluded, and 144 patients mechanically ventilated for >48 hours were analyzed. Nicotine-replacement therapy was forbidden during the study period.
  • Smoking status was assessed with the Fagerström Test of Nicotine Dependence (FTND), with dependency dichotomized at a score of 4; agitation was assessed twice daily with the Sedation-Agitation Scale (SAS >4) and delirium with the Intensive Care Delirium Screening Checklist (ICDSC >4).
  • Analyses included univariate tests, multivariate logistic regression with backward stepwise selection (c-index 0.701; 95% CI, 0.624–0.779), and a nested 1:1 matched case-control analysis matched for age (±5 years), gender, and alcoholism status.

Limitations

  • The paper states that objective measurement of tobacco addiction, such as urinary cotinine, was not performed; the small sample limits generalizability, and the lack of association between addiction level and outcomes may reflect small sample size.
  • The paper states that smoking status and endpoints were not collected in a blinded manner, sedative/analgesic use and restraint discontinuation were left to physician judgment, adjusted analyses may yield distorted associations, and baseline imbalances in age, gender, alcoholism, and septic shock were present, though the matched analysis addressed these confounders.
  • Evident in the text: the study was observational, used no standardized sedation or antipsychotic protocol, excluded acute neurologic disease, and relied on FTND responses partly from next-of-kin, which may affect assessment of nicotine dependence.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1186/cc8954

Cites

46 of 46 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 46 cited sources checked · 0 supported · 0 flagged

  • Findingown data

    In a subgroup analysis, no statistical difference was observed for development of agitation between weak and strong tobacco dependence by FTND (9/18 vs 19/26, P=0.2).

    “In a subgroup analysis comparing weak and strong tobacco dependencies according to FTND, no statistical difference was observed for the development of agitation (one or more episodes of agitation in nine patients among 18 with FTND ≤4, and in 19 patients among 26 with FTND >4, respectively; P = 0.2).”
    Quote in the paperNot a substantial claim
  • Findingown data

    Delirium was not affected by smoking status.

    “As shown in Table 2, the frequency of agitation was higher in the smoker group (64% versus 32%; P = 0.0005), but delirium was not affected by smoking status.”
    • Also stated in: § Results · plain
      “The incidence of agitation, but not delirium, increased significantly in the smoker group (64% versus 32%; P = 0.0005).”
    Quote in the paperSubstantial claim
  • Findingown data

    Need for physical restraints was higher for smokers than nonsmokers.

    “The rates of accidental removal of tubes and catheters were higher for smokers, as well as the need for supplemental sedative and analgesic medications, physical restraints, and neuroleptics in comparison with nonsmokers (Table 2).”
    Quote in the paperSubstantial claim
  • Findingnone given

    There was no center effect in the incidence of agitation.

    “There was no central effect in the incidence of agitation.”
    Quote in the paperNot a substantial claim
  • Findingown data

    The frequency of agitation was higher in smokers than nonsmokers (64% vs 32%, P=0.0005).

    “As shown in Table 2, the frequency of agitation was higher in the smoker group (64% versus 32%; P = 0.0005), but delirium was not affected by smoking status.”
    • Also stated in: § Results · plain
      “The incidence of agitation, but not delirium, increased significantly in the smoker group (64% versus 32%; P = 0.0005).”
    Quote in the paperSubstantial claim
  • May combine two claims. 25
  • Classified as probably not a substantial claim. 23

  • May combine two claims.

    Findingown data

    Among smokers, 18 (41%) had FTND ≤4 (weak dependence) and 26 (59%) had FTND >4 (strong dependence).

    “Among them, 18 (41%) patients had a score ≤4 in the FTND scale and were considered to have weak dependency, whereas 26 (59%) patients had an FTND value >4 and were considered strongly dependent on nicotine.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingown data

    Only six (14%) FTND scores were obtained exclusively from next-of-kin.

    “Thus, only six (14%) FTND scores were obtained exclusively from next-of-kin, and were recorded as well.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    44 patients were classified as smokers, with a median FTND score of 5.

    “Forty-four patients were classified as smokers, with a median FTND score of 5.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Findingown data

    144 patients were analyzed after screening 916 admissions and excluding 6 of 150 eligible.

    “In total, 916 admissions were screened for enrollment. One hundred fifty consecutive patients met the inclusion criteria. Six patients were secondarily excluded, leaving 144 patients for analysis (Figure 1).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Smokers were younger, more frequently male, and more likely to have a history of alcoholism and septic shock at ICU admission than nonsmokers.

    “Smokers were younger, and more of them were men, with more history of alcoholism and septic shock at ICU admission than had nonsmokers.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    By univariate analysis, risk factors associated with agitation were age, male gender, SOFA score, and active smoking.

    “By univariate analysis, the risk factors associated with agitation were age, male gender, SOFA score, and active smoking (Table 3).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    In the matched analysis, delirium occurred in 35% of smokers and 23% of nonsmokers, a non-significant difference (P = 0.4).

    “At least one event of delirium, n (%) | 11 (35) | 7 (23) | 0.4”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Use and doses of sedatives and analgesics did not differ between smokers and nonsmokers.

    “Overall, the rate of nosocomial infections, the use and doses of sedatives and analgesics, sedation-free days and ventilator-free days, lengths of stay in ICU, and mortality rates did not differ among groups (Table 2).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Chronic alcoholism was of borderline significance for agitation in univariate analysis (OR 1.91; 95% CI 0.95-3.83; P=0.07) and was not an independent predictor in multivariate analysis.

    “Chronic alcoholism, however, reached a level of borderline significance for agitation only with univariate analysis (OR, 1.91; 95% CI, 0.95 to 3.83; P = 0.07), and then was not identified as independent predictor for agitation in the multivariate analysis.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingown data

    Of the 44 smokers, 30 had a history of chronic alcoholism (P<0.0001).

    “Of note, of the 44 smokers, 30 had a history of chronic alcoholism (P < 0.0001, χ2 test; Table 1).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Smokers had a greater frequency of adverse events, such as accidental self-removal of tubes and catheters, and new interventions including supplemental sedation and physical restraint related to agitation events.

    “smokers had a greater frequency of adverse events, such as accidental self-removal of tubes and catheters, and new interventions including supplemental sedation and physical restraint related to agitation events.”
    • Also stated in: § Key messages · plain
      “Agitation was associated with a higher adverse-event rate, such as accidental self-removal of tubes and catheters, and new interventions including supplemental sedation and physical restraint.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    The incidence of delirium recorded in our study was 28%, at the low level of the range cited in the literature (13% to 70%).

    “The 28% incidence of delirium we recorded at the low level of the wide range cited in the literature (13% to 70%) [8,11,38-40].”
    Quote in the paperNot a substantial claim0 of 5 sources checked
    • cites [8] Dubois MJ, Bergeron N, Dumont M, Dial S, Skrobik Y: Delirium in an intensive care unit: a study of risk factors. Intensive Care Med 2001, 27: 1297-1304. 10.1007/s001340101017 source

      Not checked in the free run.

    • cites [11] Ouimet S, Kavanagh BP, Gottfried SB, Skrobik Y: Incidence, risk factors and consequences of ICU delirium. Intensive Care Med 2007, 33: 66-73. 10.1007/s00134-006-0399-8 source

      Not checked in the free run.

    • cites [38] Dubin WR, Field HL, Gastfriend DR: Postcardiotomy delirium: a critical review. J Thorac Cardiovasc Surg 1979, 77: 586-594. source

      Not checked in the free run.

    • cites [39] Lat I, McMillian W, Taylor S, Janzen JM, Papadopoulos S, Korth L, Ehtisham A, Nold J, Agarwal S, Azocar R, Burke P: The impact of delirium on clinical outcomes in mechanically ventilated surgical and trauma patients. Crit Care Med 2009, 37: 1898-1905. 10.1097/CCM.0b013e31819ffe38 source

      Not checked in the free run.

    • cites [40] Micek ST, Anand NJ, Laible BR, Shannon WD, Kollef MH: Delirium as detected by the CAM-ICU predicts restraint use among mechanically ventilated medical patients. Crit Care Med 2005, 33: 1260-1265. 10.1097/01.CCM.0000164540.58515.BF source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Nicotine-replacement therapy remains controversial in the ICU, and a retrospective study found an association between NRT and mortality.

    “Moreover, nicotine-replacement therapy (NRT) remains a controversial topic in the ICU, and a retrospective study found an association between NRT and mortality [14].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [14] Lee AH, Afessa B: The association of nicotine replacement therapy with mortality in a medical intensive care unit. Crit Care Med 2007, 35: 1517-1521. 10.1097/01.CCM.0000266537.86437.38 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Delirium and agitation occur frequently in critically ill patients, with reported frequencies of 15% to 80%.

    “Behavioral disorders such as delirium and agitation in the critically ill occur with a high frequency, ranging from 15% to 80% of patients, and have been associated with increased morbidity and risk of mortality [7-13].”
    Quote in the paperNot a substantial claim0 of 7 sources checked
    • cites [7] Chevrolet JC, Jolliet P: Clinical review: agitation and delirium in the critically ill: significance and management. Crit Care 2007, 11: 214. 10.1186/cc5787 source

      Not checked in the free run.

    • cites [8] Dubois MJ, Bergeron N, Dumont M, Dial S, Skrobik Y: Delirium in an intensive care unit: a study of risk factors. Intensive Care Med 2001, 27: 1297-1304. 10.1007/s001340101017 source

      Not checked in the free run.

    • cites [9] Ely EW, Inouye SK, Bernard GR, Gordon S, Francis J, May L, Truman B, Speroff T, Gautam S, Margolin R, Hart RP, Dittus R: Delirium in mechanically ventilated patients: validity and reliability of the confusion assessment method for the intensive care unit (CAM-ICU). JAMA 2001, 286: 2703-2710. 10.1001/jama.286.21.2703 source

      Not checked in the free run.

    • cites [10] Ely EW, Shintani A, Truman B, Speroff T, Gordon SM, Harrell FE Jr, Inouye SK, Bernard GR, Dittus RS: Delirium as a predictor of mortality in mechanically ventilated patients in the intensive care unit. JAMA 2004, 291: 1753-1762. 10.1001/jama.291.14.1753 source

      Not checked in the free run.

    • cites [11] Ouimet S, Kavanagh BP, Gottfried SB, Skrobik Y: Incidence, risk factors and consequences of ICU delirium. Intensive Care Med 2007, 33: 66-73. 10.1007/s00134-006-0399-8 source

      Not checked in the free run.

    • cites [12] Pun BT, Ely EW: The importance of diagnosing and managing ICU delirium. Chest 2007, 132: 624-636. 10.1378/chest.06-1795 source

      Not checked in the free run.

    • cites [13] Woods JC, Mion LC, Connor JT, Viray F, Jahan L, Huber C, McHugh R, Gonzales JP, Stoller JK, Arroliga AC: Severe agitation among ventilated medical intensive care unit patients: frequency, characteristics and outcomes. Intensive Care Med 2004, 30: 1066-1072. 10.1007/s00134-004-2193-9 source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Study design and conductnone given

    All degrees of agitation and delirium were confirmed by an independent physician using chart assessment.

    “All degrees of agitation and delirium were then confirmed by an independent physician by using chart assessment.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Few data exist regarding the behavioral impact of sudden nicotine abstinence in the ICU setting, except one study that identified smoking history as a risk factor for delirium in critically ill patients.

    “Few data exist in the literature regarding the behavioral impact of sudden nicotine abstinence in the ICU setting, except for one study, which identified smoking history as a risk factor for delirium in critically ill patients [8].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [8] Dubois MJ, Bergeron N, Dumont M, Dial S, Skrobik Y: Delirium in an intensive care unit: a study of risk factors. Intensive Care Med 2001, 27: 1297-1304. 10.1007/s001340101017 source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Study design and conductcitation

    Delirium was assessed twice daily by nurses or physicians until ICU discharge using the Intensive Care Delirium Screening Checklist (ICDSC).

    “Similarly, delirium was assessed for each patient twice daily by nurses or physicians until ICU discharge by using the Intensive Care Delirium Screening Checklist (ICDSC) score [22] (Additional data file 3).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [22] Bergeron N, Dubois MJ, Dumont M, Dial S, Skrobik Y: Intensive Care Delirium Screening Checklist: evaluation of a new screening tool. Intensive Care Med 2001, 27: 859-864. 10.1007/s001340100909 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductown data

    The study was a prospective observational study conducted in two adult ICUs.

    “This prospective observational study was conducted over a period running from June 2007 to April 2008 in two adult ICUs (a 22-bed medical ICU in the University Hospital of Caen, Center 1, and an eight-bed medicosurgical ICU in the tertiary Memorial Hospital of Saint-Lô, Center 2, Normandy, France).”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Study design and conductcitation

    Agitation was assessed twice daily by nurses or physicians until ICU discharge using the modified Sedation-Agitation Scale (SAS).

    “Agitation was assessed twice daily by nurses or physicians until ICU discharge, by using the modified Sedation-Agitation Scale (SAS) [21] (additional data file 2).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [21] Riker RR, Picard JT, Fraser GL: Prospective evaluation of the Sedation-Agitation Scale for adult critically ill patients. Crit Care Med 1999, 27: 1325-1329. 10.1097/00003246-199907000-00022 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Many risk factors for behavioral disorders in the critically ill have been identified, including history of hypertension and alcoholism, higher severity of acute disease, and clinical effects of sedative and analgesic agents.

    “Many risk factors, such as history of hypertension and alcoholism, higher severity of acute disease, and clinical effects of sedative and analgesic agents, have been identified in the literature [12].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [12] Pun BT, Ely EW: The importance of diagnosing and managing ICU delirium. Chest 2007, 132: 624-636. 10.1378/chest.06-1795 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductown data

    The study was approved by the local ethics committee and patients were included after informed consent.

    “The study was approved by the local ethics committee. Patients were included after informed consent of the patient or next-of-kin was obtained.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Study design and conductnone given

    Nicotine replacement therapy was forbidden during the study period.

    “NRT was forbidden during the study period.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Study design and conductreasoning

    Sample size was calculated to be at least 134 patients to detect a 30% absolute difference in agitation/delirium incidence between smokers and nonsmokers with alpha 0.05 and beta 0.2, assuming 30% baseline smoker incidence.

    “With a 30% baseline incidence of smokers in the general population, we calculated that a sample size of at least 134 patients was necessary to achieve a 30% absolute difference in agitation/delirium incidence among smokers and nonsmokers at a beta error of 0.2 and an alpha error of 0.05.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationreasoning

    Heterogeneity between studies may reflect differences in patient selection, delirium scales, and practices, including how sedation is administered, among institutions.

    “Heterogeneity between studies may also reflect differences in patient selection, delirium scales, and practices, including how sedation is administered, among institutions.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Study design and conductown data

    The consistency of results between the two statistical methods used for adjustment indicates their robustness to assumptions and increases confidence in their validity.

    “The consistency of the results between the two statistical methods used for adjustment indicates their robustness to assumptions and thus produces more confidence in their validity.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Among prior publications focused on agitation in the ICU, only one included smoking status as a variable of interest, and it did not identify smoking as a risk factor for agitation.

    “Among these publications that focused on agitation in the ICU setting, only one included smoking status as a variable of interest [13], which was, however, not identified as a risk factor for agitation.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [13] Woods JC, Mion LC, Connor JT, Viray F, Jahan L, Huber C, McHugh R, Gonzales JP, Stoller JK, Arroliga AC: Severe agitation among ventilated medical intensive care unit patients: frequency, characteristics and outcomes. Intensive Care Med 2004, 30: 1066-1072. 10.1007/s00134-004-2193-9 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In a retrospective cohort study of mechanically ventilated patients, haloperidol use was associated with lower hospital mortality, at least in part because of reduced use of sedatives and analgesics.

    “In a retrospective cohort study focusing on mechanically ventilated patients [32], haloperidol use was associated with lower hospital mortality, at least in part because of a reduced use of sedatives and analgesics.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [32] Milbrandt EB, Kersten A, Kong L, Weissfeld LA, Clermont G, Fink MP, Angus DC: Haloperidol use is associated with lower hospital mortality in mechanically ventilated patients. Crit Care Med 2005, 33: 226-229. discussion 263-225. 10.1097/01.CCM.0000150743.16005.9A source

      Not checked in the free run.

  • Classified as probably not a substantial claim. May combine two claims.

    Interpretationreasoning

    The discrepancy between our finding and Dubois and colleagues may be explained partly by the small size of our cohort, exclusion of acute neurologic diseases, absence of a standardized protocol for sedation and antipsychotic medications, and difficulties standardizing ICDSC recording.

    “This discrepancy may, however, be explained partly by the small size of our cohort, the exclusion of acute neurologic diseases in our study, the absence of a standardized protocol for sedation and antipsychotic medications, and the difficulties of standardizing the recording of the ICDSC items by both nurses and physicians.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationreasoning

    Conclusions drawn from this observational study in a small number of patients cannot be generalized.

    “conclusions drawn from this observational study in a small number of patients cannot be generalized.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Agitation has been associated with physiologic changes producing interference with mechanical ventilation, increased oxygen consumption, and failure to cooperate with treatment.

    “Agitation has been associated with physiologic changes producing interference with mechanical ventilation, increased oxygen consumption, and failure to cooperate with treatment [21].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [21] Riker RR, Picard JT, Fraser GL: Prospective evaluation of the Sedation-Agitation Scale for adult critically ill patients. Crit Care Med 1999, 27: 1325-1329. 10.1097/00003246-199907000-00022 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Physical restraints could promote the occurrence of agitation, as described in psychiatric emergency departments.

    “Physical restraints could promote, however, the occurrence of agitation, as described in psychiatric emergency departments [30].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [30] Migon MN, Coutinho ES, Huf G, Adams CE, Cunha GM, Allen MH: Factors associated with the use of physical restraints for agitated patients in psychiatric emergency rooms. Gen Hosp Psychiatry 2008, 30: 263-268. 10.1016/j.genhosppsych.2007.12.005 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationreasoning

    The lack of any association between the level of addiction and either agitation rate or most important outcomes (length of stay, organ failure, and mortality) may be the result of the small sample size.

    “The lack of any association between the level of addiction and either agitation rate or most important outcomes (length of stay, organ failure, and mortality) may also be the result of the small sample size.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Haloperidol has a number of side effects, the most problematic of which is prolongation of the corrected QT interval.

    “Haloperidol has, however, a number of side effects, the most problematic of which is prolongation of the corrected QT interval [33].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [33] Freeman BD, Dixon DJ, Coopersmith CM, Zehnbauer BA, Buchman TG: Pharmacoepidemiology of QT-interval prolonging drug administration in critically ill patients. Pharmacoepidemiol Drug Saf 2008, 17: 971-981. 10.1002/pds.1637 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationown data

    Nicotine withdrawal was associated with agitation and higher morbidities in critically ill patients.

    “Nicotine withdrawal was associated with agitation and higher morbidities in critically ill patients.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: Smokers who are abstinent from nicotine during the ICU stay experience nicotine withdrawal.
    • Rests on an assumption: Patients classified as nonsmokers (nonsmoking history or tobacco discontinuation for >6 months) do not experience nicotine withdrawal during the ICU stay.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductnone given

    Tobacco-smoking status and end points were not collected in a blinded manner by nurses and staff, and this may be considered a potential bias.

    “tobacco-smoking status and end points were not collected in a blinded manner by nurses and staff, and this point may be considered a potential bias.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationreasoning

    The discrepancy between our finding and the prior study may reflect differences in study design, case-mix population, screening instrument, and local sedation protocols.

    “This discrepancy may reflect differences in study design, case-mix population (for example, medicosurgical patients versus medical patients), screening instrument (SAS versus Motor Activity Assessment Scale [29]), and local sedation protocols.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [29] Devlin JW, Boleski G, Mlynarek M, Nerenz DR, Peterson E, Jankowski M, Horst HM, Zarowitz BJ: Motor Activity Assessment Scale: a valid and reliable sedation scale for use with mechanically ventilated patients in an adult surgical intensive care unit. Crit Care Med 1999, 27: 1271-1275. 10.1097/00003246-199907000-00008 source

      Not checked in the free run.

  • May combine two claims.

    Study design and conductown data

    A large imbalance between smokers and nonsmokers in age, gender, alcoholism, and septic shock was observed in our cohort study and may be considered as potential bias.

    “Regarding age, gender, alcoholism, and septic shock, a large imbalance between smokers and nonsmokers was observed in our cohort study and may be considered as potential bias.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Study design and conductown data

    These confounding factors are taken into account in the matched analysis that confirms our finding.

    “These confounding factors are, however, taken into account in the matched analysis that confirms our finding.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Nicotine withdrawal has been suggested as an underrecognized cause of delirium in patients with acute brain injury.

    “Nicotine withdrawal has been suggested as an underrecognized cause of delirium in patients with acute brain injury [41].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [41] Mayer SA, Chong JY, Ridgway E, Min KC, Commichau C, Bernardini GL: Delirium from nicotine withdrawal in neuro-ICU patients. Neurology 2001, 57: 551-553. source

      Not checked in the free run.

39 of 39

  • The paper relies on this without support.

    Smokers who are abstinent from nicotine during the ICU stay experience nicotine withdrawal.

    “NRT was forbidden during the study period.”
    “Nicotine withdrawal was associated with agitation and higher morbidities in critically ill patients.”

  • The paper relies on this without support.

    Patients classified as nonsmokers (nonsmoking history or tobacco discontinuation for >6 months) do not experience nicotine withdrawal during the ICU stay.

    “Patients were divided into two distinct groups: (1) smoker group, including patients with active smoking status; and (2) nonsmoker group, including patients with nonsmoking history or tobacco discontinuation for >6 months.”

  • The paper relies on this without support.

    This prospective observational study is one of the first to focus specifically on the impact of sudden nicotine abstinence in the ICU setting.

    “This prospective observational study is one of the first to focus specifically on the impact of sudden nicotine abstinence in the ICU setting.”

  • The paper relies on this without support.

    The adequate strategy for dealing with agitation is not clearly established in the ICU.

    “The adequate strategy for dealing with agitation is not clearly established in ICU.”
4 of 4

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

  • Noninvasive-ventilation failures conflict with the stated totals

    Major

    Table 2 lists 9 smoker and 12 nonsmoker NIV failures, or 21 of the 45 NIV patients. That conflicts with the stated 62% failure rate and 17 patients treated exclusively with NIV, which together imply 28 failures.

  • Matched-analysis sample size differs between sections

    Minor

    The abstract describes 28 matched pairs (56 patients), whereas the Results section describes 62 matched patients, or 31 pairs.

  • Conflicting counts for weak and strong nicotine dependence

    Minor

    The Results section reports 18 weakly dependent and 26 strongly dependent smokers, while Table 1 reports 20 and 24, respectively.

  • Strong-dependence percentage is wrong in Table 4

    Minor

    Eighteen of 31 smokers is about 58%, not the reported 64%.

    Reported 64 · recomputed 58.064516

  • Delirium threshold changes from >4 to ≥4

    Minor

    The Methods section classifies patients as delirious only when ICDSC exceeds 4, but Table 2 labels its delirium evaluation as ICDSC ≥4.

  • Matched subgroup has more febrile smokers than the full cohort

    Minor

    Table 4 reports 13 smokers with body temperature above 38.5°C in the matched subgroup, but Table 1 reports only 12 among all 44 smokers.

6 of 6

Cites

Flagged first, then by citations

Cited by

Sorted by citations

Related

Authors
Lucidarme, O., Seguin, A., Daubin, C., Ramakers, M., Terzi, N., Beck, P., Charbonneau, P., & du Cheyron, D.
Affiliations
Centre Hospitalier Universitaire de Caen Normandie (FR)
ORCID
Venue
Critical Care
Publisher
Springer Science and Business Media LLC
Published
2010-04-09
Volume
14
Issue
2
Pages
R58-R58
ISSN
1364-8535 (ISSN-L)
DOI
10.1186/cc8954
PMC
PMC2887179
OpenAlex
W2070743317
Semantic Scholar
77bbc44f5dc3143123893a41b318845403e9721b
Cited by
85
References
45
Citations by year
2026: 4 · 2025: 2 · 2024: 5 · 2023: 4 · 2022: 4 · 2021: 6 · 2020: 5 · 2019: 2 · 2018: 6 · 2017: 6 · 2016: 8 · 2015: 5 · 2014: 5 · 2013: 9 · 2012: 7
FWCI
5.16
Type
journal article
Language
en
Open access
Licence
Locations
  • Critical Care (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Critical Care and Intensive Care Medicine › Intensive Care Unit Cognitive Disorders
  • Health Sciences › Medicine › Physiology › Smoking Behavior and Cessation
  • Health Sciences › Medicine › Anesthesiology and Pain Medicine › Anesthesia and Sedative Agents
Keywords
nicotine withdrawal, nicotine abstinence, agitation, delirium, critically ill patients, mechanical ventilation, non-invasive ventilation, smoking, tobacco dependence, Fagerström Test for Nicotine Dependence, sedation, intensive care unit, behavioral disorders, mortality, length of hospital stay, physical restraint, antipsychotic drugs, alcoholism
MeSH terms
Aged, Female, France, Humans, Male, Middle Aged, Prospective Studies, Psychomotor Agitation, Respiration, Artificial, Substance Withdrawal Syndrome, Tobacco Use Disorder, Critical Illness

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-10.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-10.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review