James C. Jackson

Efficacy and safety of a paired sedation and ventilator weaning protocol for mechanically ventilated patients in intensive care (Awakening and Breathing Controlled trial): a randomised controlled trial.

BACKGROUND Approaches to removal of sedation and mechanical ventilation for critically ill patients vary widely. Our aim was to assess a protocol that paired spontaneous awakening trials (SATs)-ie, daily interruption of sedatives-with spontaneous breathing trials (SBTs). METHODS In four tertiary-care hospitals, we randomly assigned 336 mechanically ventilated patients in intensive care to management with a daily SAT followed by an SBT (intervention group; n=168) or with sedation per usual care plus a daily SBT (control group; n=168). The primary endpoint was time breathing without assistance. Data were analysed by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00097630. FINDINGS One patient in the intervention group did not begin their assigned treatment protocol because of withdrawal of consent and thus was excluded from analyses and lost to follow-up. Seven patients in the control group discontinued their assigned protocol, and two of these patients were lost to follow-up. Patients in the intervention group spent more days breathing without assistance during the 28-day study period than did those in the control group (14.7 days vs 11.6 days; mean difference 3.1 days, 95% CI 0.7 to 5.6; p=0.02) and were discharged from intensive care (median time in intensive care 9.1 days vs 12.9 days; p=0.01) and the hospital earlier (median time in the hospital 14.9 days vs 19.2 days; p=0.04). More patients in the intervention group self-extubated than in the control group (16 patients vs six patients; 6.0% difference, 95% CI 0.6% to 11.8%; p=0.03), but the number of patients who required reintubation after self-extubation was similar (five patients vs three patients; 1.2% difference, 95% CI -5.2% to 2.5%; p=0.47), as were total reintubation rates (13.8%vs 12.5%; 1.3% difference, 95% CI -8.6% to 6.1%; p=0.73). At any instant during the year after enrolment, patients in the intervention group were less likely to die than were patients in the control group (HR 0.68, 95% CI 0.50 to 0.92; p=0.01). For every seven patients treated with the intervention, one life was saved (number needed to treat was 7.4, 95% CI 4.2 to 35.5). INTERPRETATION Our results suggest that a wake up and breathe protocol that pairs daily spontaneous awakening trials (ie, interruption of sedatives) with daily spontaneous breathing trials results in better outcomes for mechanically ventilated patients in intensive care than current standard approaches and should become routine practice.

Delirium as a predictor of long-term cognitive impairment in survivors of critical illness

Objective:To test the hypothesis that duration of delirium in the intensive care unit is an independent predictor of long-term cognitive impairment after critical illness requiring mechanical ventilation. Design:Prospective cohort study. Setting:Medical intensive care unit in a large community hospital in the United States. Patients:Mechanically ventilated medical intensive care unit patients who were assessed daily for delirium while in the intensive care unit and who underwent comprehensive cognitive assessments 3 and 12 mos after discharge. Measurements and Main Results:Of 126 eligible patients, 99 survived ≥3 months after critical illness; long-term cognitive outcomes were obtained for 77 (78%) patients. Median age was 61 yrs, 51% were admitted with sepsis/acute respiratory distress syndrome, and median duration of delirium was 2 days. At 3-mo and 12-mo follow-up, 79% and 71% of survivors had cognitive impairment, respectively (with 62% and 36% being severely impaired). After adjusting for age, education, preexisting cognitive function, severity of illness, severe sepsis, and exposure to sedative medications in the intensive care unit, increasing duration of delirium was an independent predictor of worse cognitive performance—determined by averaging age-adjusted and education-adjusted T-scores from nine tests measuring seven domains of cognition—at 3-mo (p = .02) and 12-mo follow-up (p = .03). Duration of mechanical ventilation, alternatively, was not associated with long-term cognitive impairment (p = .20 and .58). Conclusions:In this study of mechanically ventilated medical intensive care unit patients, duration of delirium (which is potentially modifiable) was independently associated with long-term cognitive impairment, a common public health problem among intensive care unit survivors. (Crit Care Med 2010; 38:1513–1520

Intensive care unit delirium is an independent predictor of longer hospital stay: a prospective analysis of 261 non-ventilated patients

IntroductionDelirium occurs in most ventilated patients and is independently associated with more deaths, longer stay, and higher cost. Guidelines recommend monitoring of delirium in all intensive care unit (ICU) patients, though few data exist in non-ventilated patients. The study objective was to determine the relationship between delirium and outcomes among non-ventilated ICU patients.MethodA prospective cohort investigation of 261 consecutively admitted medical ICU patients not requiring invasive mechanical ventilation during hospitalization at a tertiary-care, university-based hospital between February 2002 and January 2003. ICU nursing staff assessed delirium and level of consciousness at least twice per day using the Confusion Assessment Method for the ICU (CAM-ICU) and Richmond Agitation-Sedation Scale (RASS). Cox regression with time-varying covariates was used to determine the independent relationship between delirium and clinical outcomes.ResultsOf 261 patients, 125 (48%) experienced at least one episode of delirium. Patients who experienced delirium were older (mean ± SD: 56 ± 18 versus 49 ± 17 years; p = 0.002) and more severely ill as measured by Acute Physiology and Chronic Health Evaluation II (APACHE II) scores (median 15, interquartile range (IQR) 10–21 versus 11, IQR 6–16; p < 0.001) compared to their non-delirious counterparts. Patients who experienced delirium had a 29% greater risk of remaining in the ICU on any given day (compared to patients who never developed delirium) even after adjusting for age, gender, race, Charlson co-morbidity score, APACHE II score, and coma (hazard ratio (HR) 1.29; 95% confidence interval (CI) 0.98–1.69, p = 0.07). Similarly, patients who experienced delirium had a 41% greater risk of remaining in the hospital after adjusting for the same covariates (HR 1.41; 95% CI 1.05–1.89, p = 0.023). Hospital mortality was higher among patients who developed delirium (24/125, 19%) versus patients who never developed delirium (8/135, 6%), p = 0.002; however, time to in-hospital death was not significant the adjusted (HR 1.27; 95% CI 0.55–2.98, p = 0.58).ConclusionDelirium occurred in nearly half of the non-ventilated ICU patients in this cohort. Even after adjustment for relevant covariates, delirium was found to be an independent predictor of longer hospital stay.

Delirium and Its Motoric Subtypes: A Study of 614 Critically Ill Patients

OBJECTIVES: To describe the motoric subtypes of delirium in critically ill patients and compare patients aged 65 and older with a younger cohort.

The Association Between Delirium and Cognitive Decline: A Review of the Empirical Literature

Delirium is a common neurobehavioral syndrome that occurs across health care settings which is associated with adverse outcomes, including death. There are limited data on long-term cognitive outcomes following delirium. This report reviews the literature regarding relationships between delirium and cognitive impairment. Psych Info and Medline searches and investigation of secondary references for all English language articles on delirium and subsequent cognitive impairment were carried out. Nine papers met inclusion criteria and documented cognitive impairment in patients following delirium. Four papers reported greater cognitive impairment among patients with delirium than matched controls. Four papers reported higher incidence of dementia in patients with a history of delirium. One study found 1 of 3 survivors of critical illness with delirium developed cognitive impairment. The evidence suggests a relationship between delirium and cognitive impairment, although significant questions remain regarding the nature of this association. Additional research on delirium-related effects on long-term cognitive outcome is needed.

Current opinions regarding the importance, diagnosis, and management of delirium in the intensive care unit: A survey of 912 healthcare professionals

ObjectiveRecently published clinical practice guidelines of the Society of Critical Care Medicine recommend monitoring for the presence of delirium in all mechanically ventilated patients because of the potential for adverse outcomes associated with this comorbidity, yet little is known about healthcare professionals’ opinions regarding intensive care unit delirium or how they manage this organ dysfunction. The aim of this survey was to assess the medical community’s beliefs and practices regarding delirium in the intensive care unit. DesignSurvey administration was conducted both without a delirium definition (phase 1) and then with a definition of delirium (phase 2). SettingCritical care meetings and continuing medical education/board review courses from October 2001 to July 2002 ParticipantsA convenience sample of physicians (n = 753), nurses (n = 113), pharmacists (n = 13), physician assistants (n = 12), respiratory care practitioners (n = 8), and others (n = 13). InterventionsSurvey. Measurements and Main ResultsParticipants completed 912 of the surveys. The majority (68%) of respondents thought that >25% of adult mechanically ventilated patients experience delirium. Delirium was considered a significant or very serious problem in the intensive care unit by 92% of healthcare professionals, yet underdiagnosis was acknowledged by 78%. Only 40% reported routinely screening for delirium, and only 16% indicated using a specific tool for delirium assessment. Delirium was considered important in the outcome of elderly and young patients by 89% and 60% of the respondents, respectively (p < .0001). The most serious complications these professionals associated with delirium were prolonged mechanical ventilation, self-injury, and respiratory difficulties. Delirium was treated with haloperidol by 66% of the respondents, with lorazepam by 12%, and with atypical antipsychotics by <5%. More than 55% administered haloperidol and lorazepam at daily doses of ≤10 mg, but some used >50 mg/day of either medication. ConclusionsMost healthcare professionals consider delirium in the intensive care unit a common and serious problem, although few actually monitor for this condition and most admit that it is underdiagnosed. Data from this survey point to a disconnect between the perceived significance of delirium in the intensive care unit and current practices of monitoring and treatment.

Overweight Is Associated With Decreased Cognitive Functioning Among School-age Children and Adolescents

Objective: Childhood overweight and obesity have increased substantially in the past two decades, raising concerns about their psychosocial and cognitive consequences. We examined the associations between academic performance (AP), cognitive functioning (CF), and increased BMI in a nationally representative sample of children.

Risk factors for post-traumatic stress disorder symptoms following critical illness requiring mechanical ventilation: a prospective cohort study

IntroductionPost-traumatic stress disorder (PTSD) has been identified in a significant portion of intensive care unit (ICU) survivors. We sought to identify factors associated with PTSD symptoms in patients following critical illness requiring mechanical ventilation.MethodsForty-three patients who were mechanically ventilated in the medical and coronary ICUs of a university-based medical center were prospectively followed during their ICU admission for delirium with the Confusion Assessment Method for the ICU. Additionally, demographic data were obtained and severity of illness was measured with the APACHE II (Acute Physiology and Chronic Health Evaluation II) score. Six months after discharge, patients were screened for PTSD symptoms by means of the Post-Traumatic Stress Syndrome 10-Questions Inventory (PTSS-10). Multiple linear regression was used to assess the association of potential risk factors with PTSS-10 scores.ResultsAt follow-up, six (14%) patients had high levels of PTSD symptoms. On multivariable analysis, women had higher PTSS-10 scores than men by a margin of 7.36 points (95% confidence interval [CI] 1.62 to 13.11; p = 0.02). Also, high levels of PTSD symptoms were less likely to occur in older patients, with symptoms declining after age 50 (p = 0.04). Finally, although causation cannot be assumed, the total dose of lorazepam received during the ICU stay was associated with PTSD symptoms; for every 10-mg increase in cumulative lorazepam dose, PTSS-10 score increased by 0.39 (95% CI 0.17 to 0.61; p = 0.04). No significant relationship was noted between severity of illness and PTSD symptoms or duration of delirium and PTSD symptoms.ConclusionHigh levels of PTSD symptoms occurred in 14% of patients six months following critical illness necessitating mechanical ventilation, and these symptoms were most likely to occur in female patients and those receiving high doses of lorazepam. High levels of PTSD symptoms were less likely to occur in older patients.

Long-term Cognitive and Psychological Outcomes in the Awakening and Breathing Controlled Trial

RATIONALE Studies have shown that reducing sedation of critically ill patients shortens time on the ventilator and in the intensive care unit (ICU). Little is known, however, of how such strategies affect long-term cognitive, psychological, and functional outcomes. OBJECTIVES To determine the long-term effects of a wake up and breathe protocol that interrupts and reduces sedative exposure in the ICU. METHODS In this a priori planned substudy conducted at one tertiary care hospital during the Awakening and Breathing Controlled Trial, a multicenter randomized controlled trial, we assessed cognitive, psychological, and functional/quality-of-life outcomes 3 and 12 months postdischarge among 180 medical ICU patients randomized to paired daily spontaneous awakening trials with spontaneous breathing trials (SBTs) or to sedation per usual care plus daily SBTs. MEASUREMENTS AND MAIN RESULTS Cognitive impairment was less common in the intervention group at 3-month follow-up (absolute risk reduction, 20.2%; 95% confidence interval, 1.5-36.1%; P = 0.03) but not at 12-month follow-up (absolute risk reduction, -1.9%; 95% CI, -21.3 to 27.1%; P = 0.89). Composite cognitive scores, alternatively, were similar in the two groups at 3-month and 12-month follow-up (P = 0.80 and 0.61, respectively), as were symptoms of depression (P = 0.59 and 0.82) and posttraumatic stress disorder (P = 0.59 and 0.97). Activities of daily living, functional status, and mental and physical quality of life were similar between groups throughout follow-up. CONCLUSIONS In this trial, management of mechanically ventilated medical ICU patients with a wake up and breathe protocol resulted in similar cognitive, psychological, and functional outcomes among patients tested 3 and 12 months post-ICU. The proven benefits of this protocol, including improved 1-year survival, were not offset by adverse long-term outcomes. Clinical trial registered with www.clinicaltrials.gov (NCT 00097630).

Apolipoprotein E4 polymorphism as a genetic predisposition to delirium in critically ill patients

Objective: To test for an association between apolipoprotein E (APOE) genotypes and duration of intensive care unit delirium. Design: Prospective, observational cohort study. Setting: A 541‐bed, community‐based teaching hospital. Patients: Fifty‐three mechanically ventilated intensive care unit patients. Interventions: None. Measurements and Main Results: All patients were managed with standardized sedation and ventilator weaning protocols as part of an ongoing clinical trial and were evaluated prospectively for delirium with the Confusion Assessment Method for the Intensive Care Unit (CAM‐ICU). DNA was extracted from whole blood samples obtained on enrollment, and APOE genotype was determined using polymerase chain reaction followed by restriction enzyme digestion by investigators blinded to the clinical information. Delirium occurred in 47 (89%) patients at some point during the intensive care unit stay. Of the 53 patients, 12 (23%) had an APOE4 allele (APOE4+) and 41 (77%) had only APOE2 or APOE3 alleles (APOE4−). APOE4+ patients were younger (53.2 ± 21.9 vs. 65.4 ± 13.4, p = .08) and less often admitted for pneumonia (0% vs. 29.3%, p = .05) compared with APOE4− patients, yet they had a duration of delirium that was twice as long: median (interquartile range), 4 (3, 4.5) vs. 2 (1, 4) days (p = .05). No other clinical outcomes were significantly different between the APOE4+ and APOE4− patients. Using multivariable regression analysis to adjust for age, admission diagnosis of sepsis or acute respiratory distress syndrome or pneumonia, severity of illness, and duration of coma, the presence of APOE4 allele was the strongest predictor of delirium duration (odds ratio, 7.32; 95% confidence interval, 1.82–29.51, p = .005). Conclusions: APOE4 allele represents the first demonstrated genetic predisposition to longer duration of delirium in humans.