Kendiss Olafson

Critically Ill Patients With 2009 Influenza A(H1N1) Infection in Canada

CONTEXT Between March and July 2009, the largest number of confirmed cases of 2009 influenza A(H1N1) infection occurred in North America. OBJECTIVE To describe characteristics, treatment, and outcomes of critically ill patients in Canada with 2009 influenza A(H1N1) infection. DESIGN, SETTING, AND PATIENTS A prospective observational study of 168 critically ill patients with 2009 influenza A(H1N1) infection in 38 adult and pediatric intensive care units (ICUs) in Canada between April 16 and August 12, 2009. MAIN OUTCOME MEASURES The primary outcome measures were 28-day and 90-day mortality. Secondary outcomes included frequency and duration of mechanical ventilation and duration of ICU stay. RESULTS Critical illness occurred in 215 patients with confirmed (n = 162), probable (n = 6), or suspected (n = 47) community-acquired 2009 influenza A(H1N1) infection. Among the 168 patients with confirmed or probable 2009 influenza A(H1N1), the mean (SD) age was 32.3 (21.4) years; 113 were female (67.3%) and 50 were children (29.8%). Overall mortality among critically ill patients at 28 days was 14.3% (95% confidence interval, 9.5%-20.7%). There were 43 patients who were aboriginal Canadians (25.6%). The median time from symptom onset to hospital admission was 4 days (interquartile range [IQR], 2-7 days) and from hospitalization to ICU admission was 1 day (IQR, 0-2 days). Shock and nonpulmonary acute organ dysfunction was common (Sequential Organ Failure Assessment mean [SD] score of 6.8 [3.6] on day 1). Neuraminidase inhibitors were administered to 152 patients (90.5%). All patients were severely hypoxemic (mean [SD] ratio of Pao(2) to fraction of inspired oxygen [Fio(2)] of 147 [128] mm Hg) at ICU admission. Mechanical ventilation was received by 136 patients (81.0%). The median duration of ventilation was 12 days (IQR, 6-20 days) and ICU stay was 12 days (IQR, 5-20 days). Lung rescue therapies included neuromuscular blockade (28% of patients), inhaled nitric oxide (13.7%), high-frequency oscillatory ventilation (11.9%), extracorporeal membrane oxygenation (4.2%), and prone positioning ventilation (3.0%). Overall mortality among critically ill patients at 90 days was 17.3% (95% confidence interval, 12.0%-24.0%; n = 29). CONCLUSION Critical illness due to 2009 influenza A(H1N1) in Canada occurred rapidly after hospital admission, often in young adults, and was associated with severe hypoxemia, multisystem organ failure, a requirement for prolonged mechanical ventilation, and the frequent use of rescue therapies.

Intraventricular injection of human immunodeficiency virus type 1 (HIV-1) Tat protein causes inflammation, gliosis, apoptosis, and ventricular enlargement

To determine the role of the Tat protein of the human immunodeficiency virus type 1 (HIV-1) in the pathogenesis of HIV-1 associated dementia, recombinant Tat was injected intraventricularly as a single or repeated dose into male Sprague- Dawley rats. Histopathological evaluation showed an initial infiltration of neutrophils one day after Tat injection, followed by macrophages and lymphocytes by 7 days. Tat-injected brains also exhibited astrocytosis, apoptotic cells, and ventricular enlargement 7 days following the last injection. Nuclear magnetic resonance spectroscopic analysis of tissue extracts of hippocampi from Tat-injected rats showed a decrease in the glutamate/g aminobutyric acid ratio. We conclude that the transient extracellular exposure of the central nervous system to Tat protein of HIV can cause a cascade of events leading to the influx of inflammatory cells, glial cell activation, and neurotoxicity.

High occupancy increases the risk of early death or readmission after transfer from intensive care

Objective: To determine whether a lack of intensive care unit beds was leading to premature patient discharge from the intensive care unit and subsequent early readmission or death. Design: Prospective cohort study. Setting: A single Canadian tertiary care teaching hospital. Patients: All intensive care unit admissions between January 1, 1989 and December 31, 1996 were collected prospectively for inclusion in a registry database. Interventions: None. Measurements and Main Results: There was a positive correlation between early readmission or death and average quarterly intensive care unit percent occupancy (p = .001). During the study period, 8693 patients experienced 10,185 admissions to intensive care. Of the 8222 patients remaining under active treatment (patients under palliative care were excluded), there were 455 (5.5%) adverse events (431 intensive care unit readmissions and 24 deaths) in the first 7 days post intensive care unit discharge. Patients requiring a new surgical intervention with postoperative intensive care unit admission were not considered readmissions. In a multivariate analysis, significant risk factors for an adverse event included age >35 yrs, particular diagnoses (respiratory diagnoses, sepsis, neurosurgery, thoracic surgery, and gastrointestinal diagnoses), Acute Physiology and Chronic Health Evaluation II score, and intensive care unit length of stay. Discharge from the intensive care unit at a time of no vacancy was also a significant risk factor for intensive care unit readmission or unexpected death with an adjusted relative risk of 1.56 (95% confidence interval 1.05, 2.31). Conclusions: Increased patient occupancy within an intensive care unit is associated with an increased risk of early death or intensive care unit readmission post intensive care unit discharge. Overloading the capacity of an intensive care unit to care for critically ill patients may affect physician decision‐making, resulting in premature discharge from the intensive care unit.

Prevalence, risk factors, and outcomes of delirium in mechanically ventilated adults.

Objective:Delirium is common during critical illness and associated with adverse outcomes. We compared characteristics and outcomes of delirious and nondelirious patients enrolled in a multicenter trial comparing protocolized sedation with protocolized sedation plus daily sedation interruption. Design:Randomized trial. Setting:Sixteen North American medical and surgical ICUs. Patients:Four hundred thirty critically ill, mechanically ventilated adults. Interventions:All patients had hourly titration of opioid and benzodiazepine infusions using a validated sedation scale. For patients in the interruption group, infusions were resumed, if indicated, at half of previous doses. Delirium screening occurred daily; positive screening was defined as an Intensive Care Delirium Screening Checklist score of 4 or more at any time. Measurements and Main Results:Delirium was diagnosed in 226 of 420 assessed patients (53.8%). Coma was identified in 32.7% of delirious compared with 22.7% of nondelirious patients (p = 0.03). The median time to onset of delirium was 3.5 days (interquartile range, 2–7), and the median duration of delirium was 2 days (interquartile range, 1–4). Delirious patients were more likely to be male (61.1% vs 46.6%; p = 0.005), have a surgical/trauma diagnosis (21.2% vs 11.0%; p = 0.030), and history of tobacco (31.5% vs 16.2%; p = 0.002) or alcohol use (34.6% vs 20.9%; p = 0.009). Patients with positive delirium screening had longer duration of ventilation (13 vs 7 d; p < 0.001), ICU stay (12 vs 8 d; p < 0.0001), and hospital stay (24 vs 15 d; p < 0.0001). Delirious patients were more likely to be physically restrained (86.3% vs 76.7%; p = 0.014) and undergo tracheostomy (34.6% vs 15.5%; p < 0.0001). Antecedent factors independently associated with delirium onset were restraint use (hazard ratio, 1.87; 95% CI, 1.33–2.63; p = 0.0003), antipsychotic administration (hazard ratio, 1.67; 95% CI, 1.005–2.767; p = 0.047), and midazolam dose (hazard ratio, 0.998; 95% CI, 0.997–1.0; p = 0.049). There was no difference in delirium prevalence or duration between the interruption and control groups. Conclusion:In mechanically ventilated adults, delirium was common and associated with longer duration of ventilation and hospitalization. Physical restraint was most strongly associated with delirium.

Rates of readmission and death associated with leaving hospital against medical advice: a population-based study

Background: Leaving hospital against medical advice may have adverse consequences. Previous studies have been limited by evaluating specific types of patients, small sample sizes and incomplete determination of outcomes. We hypothesized that leaving hospital against medical advice would be associated with increases in subsequent readmission and death. Methods: In a population-based analysis involving all adults admitted to hospital and discharged alive in Manitoba from Apr. 1, 1990, to Feb. 28, 2009, we evaluated all-cause 90-day mortality and 30-day hospital readmission. We used multivariable regression, adjusted for age, sex, socioeconomic status, year of hospital admission, patient comorbidities, hospital diagnosis, past frequency of admission to hospital, having previously left hospital against medical advice and data clustering (patients with multiple admissions). For readmission, we assessed both between-person and within-person effects of leaving hospital against medical advice. Results: Leaving against medical advice occurred in 21 417 of 1 916 104 index hospital admissions (1.1%), and was associated with higher adjusted rates of 90-day mortality (odds ratio [OR] 2.51, 95% confidence interval [CI] 2.18–2.89), and 30-day hospital readmission (within-person OR 2.10, CI 1.99–2.21; between-person OR 3.04, CI 2.79–3.30). In our additional analyses, elevated rates of readmission and death associated with leaving against medical advice were manifest within 1 week and persisted for at least 180 days after discharge. Interpretation: Adults who left the hospital against medical advice had higher rates of hospital readmission and death. The persistence of these effects suggests that they are not solely a result of incomplete treatment of acute illness. Interventions aimed at reducing these effects may need to include longitudinal interventions extending beyond admission to hospital.

The accuracy of administrative data for identifying the presence and timing of admission to intensive care units in a Canadian province.

Background:A prerequisite for using administrative data to study the care of critically ill patients in intensive care units (ICUs) is that it accurately identifies such care. Only limited data exist on this subject. Objective:To assess the accuracy of administrative data in the Canadian province of Manitoba for identifying the existence, number, and timing of admissions to adult ICUs. Research Design:For the period 1999 to 2008, we compared information about ICU care from Manitoba hospital abstracts, with the criterion standard of a clinical ICU database that includes all admissions to adult ICUs in its largest city of Winnipeg. Comparisons were made before and after a national change in administrative data requirements that mandated specific data elements identifying the existence and timing of ICU care. Results:In both time intervals, hospital abstracts were extremely accurate in identifying the presence of ICU care, with positive predictive values exceeding 98% and negative predictive values exceeding 99%. Administrative data correctly identified the number of separate ICU admissions for 93% of ICU-containing hospitalizations; inaccuracy increased with more ICU stays per hospitalization. Hospital abstracts were highly accurate for identifying the timing of ICU care, but only for hospitalizations containing a single ICU admission. Conclusions:Under current national-reporting requirements, hospital administrative data in Canada can be used to accurately identify and quantify ICU care. The high accuracy of Manitoba administrative data under the previous reporting standards, which lacked standardized coding elements specific to ICU care, may not be generalizable to other Canadian jurisdictions.

Epidemiology of critically ill patients in intensive care units: a population-based observational study

IntroductionEpidemiologic assessment of critically ill people in Intensive Care Units (ICUs) is needed to ensure the health care system can meet current and future needs. However, few such studies have been published.MethodsPopulation-based analysis of all adult ICU care in the Canadian province of Manitoba, 1999 to 2007, using administrative data. We calculated age-adjusted rates and trends of ICU care, overall and subdivided by age, sex and income.ResultsIn 2007, Manitoba had a population of 1.2 million, 118 ICU beds in 21 ICUs, for 9.8 beds per 100,000 population. Approximately 0.72% of men and 0.47% of women were admitted to ICUs yearly. The age-adjusted, male:female rate ratio was 1.75 (95% CI 1.64 to 1.88). Mean age was 64.5 ± 16.4 years. Rates rose rapidly after age 40, peaked at age 75 to 80, and declined for the oldest age groups. Rates were higher among residents of lower income areas, for example declining from 7.9 to 4.4 per 100,000 population from the poorest to the wealthiest income quintiles (p <0.0001). Rates of ICU admission slowly declined over time, while cumulative yearly ICU bed-days slowly rose; changes were age-dependent, with faster declines in admission rates with older age. There was a high rate of recidivism; 16% of ICU patients had received ICU care previously.ConclusionsThese temporal trends in ICU admission rates and cumulative bed-days used have significant implications for health system planning. The differences by age, sex and socioeconomic status, and the high rate of recidivism require further research to clarify their causes, and to devise strategies for reducing critical illness in high-risk groups.

A population-based analysis of leaving the hospital against medical advice: incidence and associated variables

BackgroundPrior studies of patients leaving hospital against medical advice (AMA) have been limited by not being population-based or assessing only one type of patient.MethodsWe used administrative data at the Manitoba Centre for Health Policy to evaluate all adult residents of Manitoba, Canada discharged alive from acute care hospitals between April 1, 1990 and February 28, 2009. We identified the rate of leaving AMA, and used multivariable logistic regression to identify socio-demographic and diagnostic variables associated with leaving AMA.ResultsOf 1 916 104 live hospital discharges, 21 417 (1.11%) ended with the patient leaving AMA. The cohort contained 610 187 individuals, of whom 12 588 (2.06%) left AMA once and another 2 986 (0.49%) left AMA more than once. The proportion of AMA discharges did not change over time. Alcohol and drug abuse was the diagnostic group with the highest proportion of AMA discharges, at 11.71%. Having left AMA previously had the strongest association with leaving AMA (odds ratio 170, 95% confidence interval 156–185). Leaving AMA was more common among men, those with lower average household incomes, histories of alcohol or drug abuse or HIV/AIDS. Major surgical procedures were associated with a much lower chance of leaving the hospital AMA.ConclusionsThe rate of leaving hospital AMA did not systematically change over time, but did vary based on patient and illness characteristics. Having left AMA in the past was highly predictive of subsequent AMA events.

Constructing episodes of inpatient care: data infrastructure for population-based research.

BackgroundDatabases used to study the care of patients in hospitals and Intensive Care Units (ICUs) typically contain a separate entry for each segment of hospital or ICU care. However, it is not uncommon for patients to be transferred between hospitals and/or ICUs, and when transfers occur it is necessary to combine individual entries to accurately reconstruct the complete episodes of hospital and ICU care. Failure to do so can lead to erroneous lengths-of-stay, and rates of admissions, readmissions, and death.MethodsThis study used a clinical ICU database and administrative hospital abstracts for the adult population of Manitoba, Canada from 2000–2008. We compared five methods for identifying patient transfers and constructing hospital episodes, and the ICU episodes contained within them. Method 1 ignored transfers. Methods 2–5 considered the time gap between successive entries (≤1 day vs. ≤2 days), with or without use of data fields indicating inter-hospital transfer. For the five methods we compared the resulting number and lengths of hospital and ICU episodes.ResultsDuring the study period, 48,551 hospital abstracts contained 53,246 ICU records. For Method 1 these were also the number of hospital and ICU episodes, respectively. Methods 2–5 gave remarkably similar results, with transfers included in approximately 25% of ICU-containing hospital episodes, and 10% of ICU episodes. Comparison with Method 1 showed that failure to account for such transfers resulted in overestimating the number of episodes by 7-10%, and underestimating mean or median lengths-of-stay by 9-30%.ConclusionsIn Manitoba is it not uncommon for critically ill patients to be transferred between hospitals and between ICUs. Failure to account for transfers resulted in inaccurate assessment of parameters relevant to researchers, clinicians, and policy-makers. The details of the method used to identify transfers, at least among the variations tested, made relatively little difference. In addition, we showed that these methods for constructing episodes of hospital and ICU care can be implemented in a large, complex dataset.

Prevalence, risk factors, and outcomes associated with physical restraint use in mechanically ventilated adults

PURPOSE The purpose was to describe characteristics and outcomes of restrained and nonrestrained patients enrolled in a randomized trial of protocolized sedation compared with protocolized sedation plus daily sedation interruption and to identify patient and treatment factors associated with physical restraint. METHODS This was a post hoc secondary analysis using Cox proportional hazards modeling adjusted for center- and time-varying covariates to evaluate predictors of restraint use. RESULTS A total of 328 (76%) of 430 patients were restrained for a median of 4 days. Restrained patients received higher daily doses of benzodiazepines (105 vs 41 mg midazolam equivalent, P < .0001) and opioids (1524 vs 919 μg fentanyl equivalents, P < .0001), more days of infusions (benzodiazepines 6 vs 4, P < .0001; opioids 7 vs 5, P = .02), and more daily benzodiazepine boluses (0.2 vs 0.1, P < .0001). More restrained patients received haloperidol (23% vs 12%, P = .02) and atypical antipsychotics (17% vs 4%, P = .003). More restrained patients experienced unintentional device removal (26% vs 3%, P < .001) and required reintubation (8% vs 1%, P = .01). In the multivariable analysis, alcohol use was associated with decreased risk of restraint (hazard ratio, 0.22; 95% confidence interval, 0.08-0.58). CONCLUSIONS Physical restraint was common in mechanically ventilated adults managed with a sedation protocol. Restrained patients received more opioids and benzodiazepines. Except for alcohol use, patient characteristics and treatment factors did not predict restraint use.