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1.  Acquired bloodstream infection in the intensive care unit: incidence and attributable mortality 
Critical Care  2011;15(2):R100.
To estimate the incidence of intensive care unit (ICU)-acquired bloodstream infection (BSI) and its independent effect on hospital mortality.
We retrospectively studied acquisition of BSI during admissions of >72 hours to adult ICUs from two university-affiliated hospitals. We obtained demographics, illness severity and co-morbidity data from ICU databases and microbiological diagnoses from departmental electronic records. We assessed survival at hospital discharge or at 90 days if still hospitalized.
We identified 6339 ICU admissions, 330 of which were complicated by BSI (5.2%). Median time to first positive culture was 7 days (IQR 5-12). Overall mortality was 23.5%, 41.2% in patients with BSI and 22.5% in those without. Patients who developed BSI had higher illness severity at ICU admission (median APACHE III score: 79 vs. 68, P < 0.001). After controlling for illness severity and baseline demographics by Cox proportional-hazard model, BSI remained independently associated with risk of death (hazard ratio from diagnosis 2.89; 95% confidence interval 2.41-3.46; P < 0.001). However, only 5% of the deaths in this model could be attributed to acquired-BSI, equivalent to an absolute decrease in survival of 1% of the total population. When analyzed by microbiological classification, Candida, Staphylococcus aureus and gram-negative bacilli infections were independently associated with increased risk of death. In a sub-group analysis intravascular catheter associated BSI remained associated with significant risk of death (hazard ratio 2.64; 95% confidence interval 1.44-4.83; P = 0.002).
ICU-acquired BSI is associated with greater in-hospital mortality, but complicates only 5% of ICU admissions and its absolute effect on population mortality is limited. These findings have implications for the design and interpretation of clinical trials.
PMCID: PMC3219371  PMID: 21418635
2.  Hospital mortality is associated with ICU admission time 
Intensive Care Medicine  2010;36(10):1765-1771.
Previous studies have shown that patients admitted to the intensive care unit (ICU) after “office hours” are more likely to die. However these results have been challenged by numerous other studies. We therefore analysed this possible relationship between ICU admission time and in-hospital mortality in The Netherlands.
This article relates time of ICU admission to hospital mortality for all patients who were included in the Dutch national ICU registry (National Intensive Care Evaluation, NICE) from 2002 to 2008. We defined office hours as 08:00–22:00 hours during weekdays and 09:00–18:00 hours during weekend days. The weekend was defined as from Saturday 00:00 hours until Sunday 24:00 hours. We corrected hospital mortality for illness severity at admission using Acute Physiology and Chronic Health Evaluation II (APACHE II) score, reason for admission, admission type, age and gender.
A total of 149,894 patients were included in this analysis. The relative risk (RR) for mortality outside office hours was 1.059 (1.031–1.088). Mortality varied with time but was consistently higher than expected during “off hours” and lower during office hours. There was no significant difference in mortality between different weekdays of Monday to Thursday, but mortality increased slightly on Friday (RR 1.046; 1.001–1.092). During the weekend the RR was 1.103 (1.071–1.136) in comparison with the rest of the week.
Hospital mortality in The Netherlands appears to be increased outside office hours and during the weekends, even when corrected for illness severity at admission. However, incomplete adjustment for certain confounders might still play an important role. Further research is needed to fully explain this difference.
Electronic supplementary material
The online version of this article (doi:10.1007/s00134-010-1918-1) contains supplementary material, which is available to authorized users.
PMCID: PMC2940016  PMID: 20549184
Hospital mortality; Admission time; ICU; Severity of illness; APACHE II
3.  The Impact of Acute Brain Dysfunction in the Outcomes of Mechanically Ventilated Cancer Patients 
PLoS ONE  2014;9(1):e85332.
Delirium and coma are a frequent source of morbidity for ICU patients. Several factors are associated with the prognosis of mechanically ventilated (MV) cancer patients, but no studies evaluated delirium and coma (acute brain dysfunction). The present study evaluated the frequency and impact of acute brain dysfunction on mortality.
The study was performed at National Cancer Institute, Rio de Janeiro, Brazil. We prospectively enrolled patients ventilated >48 h with a diagnosis of cancer. Acute brain dysfunction was assessed during the first 14 days of ICU using RASS/CAM-ICU. Patients were followed until hospital discharge. Univariate and multivariable analysis were performed to evaluate factors associated with hospital mortality.
170 patients were included. 73% had solid tumors, age 65 [53–72 (median, IQR 25%–75%)] years. SAPS II score was 54[46–63] points and SOFA score was (7 [6]–[9]) points. Median duration of MV was 13 (6–21) days and ICU stay was 14 (7.5–22) days. ICU mortality was 54% and hospital mortality was 66%. Acute brain dysfunction was diagnosed in 161 patients (95%). Survivors had more delirium/coma-free days [4(1,5–6) vs 1(0–2), p<0.001]. In multivariable analysis the number of days of delirium/coma-free days were associated with better outcomes as they were independent predictors of lower hospital mortality [0.771 (0.681 to 0.873), p<0.001].
Acute brain dysfunction in MV cancer patients is frequent and independently associated with increased hospital mortality. Future studies should investigate means of preventing or mitigating acute brain dysfunction as they may have a significant impact on clinical outcomes.
PMCID: PMC3899009  PMID: 24465538
4.  Factors influencing physical functional status in intensive care unit survivors two years after discharge 
BMC Anesthesiology  2013;13:11.
Studies suggest that in patients admitted to intensive care units (ICU), physical functional status (PFS) improves over time, but does not return to the same level as before ICU admission. The goal of this study was to assess physical functional status two years after discharge from an ICU and to determine factors influencing physical status in this population.
The study reviewed all patients admitted to two non-trauma ICUs during a one-year period and included patients with age ≥ 18 yrs, ICU stay ≥ 24 h, and who were alive 24 months after ICU discharge. To assess PFS, Karnofsky Performance Status Scale scores and Lawton-Instrumental Activities of Daily Living (IADL) scores at ICU admission (K-ICU and L-ICU) were compared to the scores at the end of 24 months (K-24mo and L-24mo). Data at 24 months were obtained through telephone interviews.
A total of 1,216 patients were eligible for the study. Twenty-four months after ICU discharge, 499 (41.6%) were alive, agreed to answer the interview, and had all hospital data available. PFS (K-ICU: 86.6 ± 13.8 vs. K-24mo: 77.1 ± 19.6, p < 0.001) and IADL (L-ICU: 27.0 ± 11.7 vs. L-24mo: 22.5 ± 11.5, p < 0.001) declined in patients with medical and unplanned surgical admissions. Most strikingly, the level of dependency increased in neurological patients (K-ICU: 86 ± 12 vs. K-24mo: 64 ± 21, relative risk [RR] 2.6, 95% CI, 1.8–3.6, p < 0.001) and trauma patients (K-ICU: 99 ± 2 vs. K-24mo: 83 ± 21, RR 2.7, 95% CI, 1.6–4.6, p < 0.001). The largest reduction in the ability to perform ADL occurred in neurological patients (L-ICU: 27 ± 7 vs. L-24mo: 15 ± 12, RR 3.3, 95% CI, 2.3–4.6 p < 0.001), trauma patients (L-ICU: 32 ± 0 vs. L-24mo: 25 ± 11, RR 2.8, 95% CI, 1.5–5.1, p < 0.001), patients aged ≥ 65 years (RR 1.4, 95% CI, 1.07–1.86, p = 0.01) and those who received mechanical ventilation for ≥ 8 days (RR 1.48, 95% CI, 1.02–2.15, p = 0.03).
Twenty-four months after ICU discharge, PFS was significantly poorer in patients with neurological injury, trauma, age ≥ 65 tears, and mechanical ventilation ≥ 8 days. Future studies should focus on the relationship between PFS and health-related quality of life in this population.
PMCID: PMC3701489  PMID: 23773812
Activities of Daily Living; Physical Functional Status; Intensive Care Unit; Long-term Care; Mortality; Prognosis; Health-related Quality of Life
5.  Early versus late intravenous insulin administration in critically ill patients 
Intensive care medicine  2008;34(5):881-887.
To investigate whether timing of intensive insulin therapy (IIT) after intensive care unit (ICU) admission influences outcome.
Design and setting
Single-center prospective cohort study in the 14-bed medical ICU of a 1,171-bed tertiary teaching hospital.
The study included 127 patients started on ITT within 48 h of ICU admission (early group) and 51 started on ITT thereafter (late group); the groups did not differ in age, gender, race, BMI, APACHE III, ICU steroid use, admission diagnosis, or underlying comorbidities.
Measurements and results
The early group had more ventilator-free days in the first 28 days after ICU admission (median 12 days, IQR 0–24, vs. 1 day, 0–11), shorter ICU stay (6 days, IQR 3–11, vs. 11 days, vs. 7–17), shorter hospital stay (15 days, IQR 9–30, vs. 25 days, 13–43), lower ICU mortality (OR 0.48), and lower hospital mortality (OR 0.27). On multivariate analysis, early therapy was still associated with decreased hospital mortality (ORadj 0.29). The strength and direction of association favoring early IIT was consistent after propensity score modeling regardless of method used for analysis.
Early IIT was associated with better outcomes. Our results raise questions about the assumption that delayed administration of IIT has the same benefit as early therapy. A randomized study is needed to determine the optimal timing of therapy.
PMCID: PMC2486366  PMID: 18180902
Hyperglycemia; Critical illness; Insulin; Mortality
6.  A Randomized Trial of Nighttime Physician Staffing in an Intensive Care Unit 
The New England journal of medicine  2013;368(23):2201-2209.
Increasing numbers of intensive care units (ICUs) are adopting the practice of nighttime intensivist staffing despite the lack of experimental evidence of its effectiveness.
We conducted a 1-year randomized trial in an academic medical ICU of the effects of nighttime staffing with in-hospital intensivists (intervention) as compared with nighttime coverage by daytime intensivists who were available for consultation by telephone (control). We randomly assigned blocks of 7 consecutive nights to the intervention or the control strategy. The primary outcome was patients' length of stay in the ICU. Secondary outcomes were patients' length of stay in the hospital, ICU and in-hospital mortality, discharge disposition, and rates of readmission to the ICU. For length-of-stay outcomes, we performed time-to-event analyses, with data censored at the time of a patient's death or transfer to another ICU.
A total of 1598 patients were included in the analyses. The median Acute Physiology and Chronic Health Evaluation (APACHE) III score (in which scores range from 0 to 299, with higher scores indicating more severe illness) was 67 (interquartile range, 47 to 91), the median length of stay in the ICU was 52.7 hours (interquartile range, 29.0 to 113.4), and mortality in the ICU was 18%. Patients who were admitted on intervention days were exposed to nighttime intensivists on more nights than were patients admitted on control days (median, 100% of nights [interquartile range, 67 to 100] vs. median, 0% [interquartile range, 0 to 33]; P<0.001). Nonetheless, intensivist staffing on the night of admission did not have a significant effect on the length of stay in the ICU (rate ratio for the time to ICU discharge, 0.98; 95% confidence interval [CI], 0.88 to 1.09; P = 0.72), ICU mortality (relative risk, 1.07; 95% CI, 0.90 to 1.28), or any other end point. Analyses restricted to patients who were admitted at night showed similar results, as did sensitivity analyses that used different definitions of exposure and outcome.
In an academic medical ICU in the United States, nighttime in-hospital intensivist staffing did not improve patient outcomes. (Funded by University of Pennsylvania Health System and others; number, NCT01434823.)
PMCID: PMC3732473  PMID: 23688301
7.  Prognosis and ICU outcome of systemic vasculitis 
BMC Anesthesiology  2013;13:27.
Systemic vasculitis may cause life threatening complications requiring admission to an intensive care unit (ICU). The aim of this study was to evaluate outcomes of systemic vasculitis patients admitted to the ICU and to identify prognosis factors.
During a ten-year period, records of 31 adult patients with systemic vasculitis admitted to ICUs (median age: 63 y.o, sex ratio M/F: 21/10, SAPS II: 40) were reviewed including clinical and biological parameters, use of mechanical ventilation, catecholamine or/and dialysis support. Mortality was assessed and data were analyzed to identify predictive factors of outcome.
Causes of ICU admissions were active manifestation of vasculitis (n = 19), septic shock (n = 8) and miscellaneous (n = 4). Sixteen patients (52%) died in ICU. By univariate analysis, mortality was associated with higher SOFA (p = 0.006) and SAPS II (p = 0.004) scores. The need for a catecholamine support or/and a renal replacement therapy, and the occurrence of an ARDS significantly worsen the prognosis. By multivariate analysis, only SAPS II (Odd ratio: 1.16, 95% CI [1.01; 1.33]) and BVAS scores (Odd ratio: 1.16, 95% CI = [1.01; 1.34]) were predictive of mortality.
The mortality rate of severe vasculitis requiring an admission to ICU was high. High levels of SAPS II and BVAS scores at admission were predictive of mortality.
PMCID: PMC4016298  PMID: 24083831
Vasculitis; Outcome; Mortality; Intensive care unit; BVAS
8.  Hospital mortality among major trauma victims admitted on weekends and evenings: a cohort study 
Patient care may be inconsistent during off hours. We sought to determine whether victims of major trauma admitted to hospital on evenings, nights, and weekends suffer increased mortality rates. All victims of major trauma admitted to all four major acute care hospitals in the Calgary Health Region between April 1, 2002 and March 31, 2006 were included. Clinical and outcome information was obtained from regional databases. Weekends were defined as anytime Saturday or Sunday, evenings as 18:00–22:59, and nights as 23:00–07:59.
Four thousand patients were included; 2,901 (73%) were male, the median age was 39.5 [inter-quartile range (IQR), 22.4–58.2] years, and the median injury severity score (ISS) was 20 (IQR, 16–26). Thirty-five percent (1,405) of patients were admitted on a weekend, 30% (1,197) during evenings, and 36% (1,422) at night. Seventy-eight percent (3,106) of cases presented during the "after hours" (evenings, nights, and/or weekends). The in-hospital case-fatality rate was 447 (11%), and was not significantly different during daytime (165/1,381; 37%), evening (128/1,197; 30%), and night (154/1,422; 36%) admissions (p = 0.53), or among patients admitted on weekends as compared to weekdays (157/1,405; 11% vs. 290/2,595; 11%; p = 1.0). Admission during the after hours as compared to business hours (343/3,106; 11% vs. 104/894; 12%; p = 0.63) did not increased risk. A multivariable logistic regression model was developed to assess factors associated with in-hospital death (n = 3,891). Neither admission on weekends nor on evenings or nights increased the risk for in-hospital mortality.
In our region, the time of admission during the day or day of the week does not influence the risk for adverse outcome and may reflect our highly developed multi-hospital acute care and trauma system.
PMCID: PMC2731032  PMID: 19635157
9.  Variability of Intensive Care Admission Decisions for the Very Elderly 
PLoS ONE  2012;7(4):e34387.
Although increasing numbers of very elderly patients are requiring intensive care, few large sample studies have investigated ICU admission of very elderly patients. Data on pre triage by physicians from other specialities is limited. This observational cohort study aims at examining inter-hospital variability of ICU admission rates and its association with patients' outcomes. All patients over 80 years possibly qualifying for ICU admission who presented to the emergency departments (ED) of 15 hospitals in the Paris (France) area during a one-year period were prospectively included in the study. Main outcome measures were ICU eligibility, as assessed by the ED and ICU physicians; in-hospital mortality; and vital and functional status 6 months after the ED visit. 2646 patients (median age 86; interquartile range 83–91) were included in the study. 94% of participants completed follow-up (n = 2495). 12.4% (n = 329) of participants were deemed eligible for ICU admission by ED physicians and intensivists. The overall in-hospital and 6-month mortality rates were respectively 27.2% (n = 717) and 50.7% (n = 1264). At six months, 57.5% (n = 1433) of patients had died or had a functional deterioration. Rates of patients deemed eligible for ICU admission ranged from 5.6% to 38.8% across the participating centers, and this variability persisted after adjustment for patients' characteristics. Despite this variability, we found no association between level of ICU eligibility and either in-hospital death or six-month death or functional deterioration. In France, the likelihood that a very elderly person will be admitted to an ICU varies widely from one hospital to another. Influence of intensive care admission on patients' outcome remains unclear.
Trial Registration NCT00912600
PMCID: PMC3324496  PMID: 22509296
10.  Occurrence of delirium is severely underestimated in the ICU during daily care 
Intensive Care Medicine  2009;35(7):1276-1280.
Delirium is associated with prolonged intensive care unit (ICU) stay and higher mortality. Therefore, the recognition of delirium is important. We investigated whether intensivists and ICU nurses could clinically identify the presence of delirium in ICU patients during daily care.
All ICU patients in a 3-month period who stayed for more than 48 h were screened daily for delirium by attending intensivists and ICU nurses. Patients were screened independently for delirium by a trained group of ICU nurses who were not involved in the daily care of the patients under study. The Confusion Assessment Method for the ICU (CAM-ICU) was used as a validated screening instrument for delirium. Values are expressed as median and interquartile range (IQR; P25–P75).
During the study period, 46 patients (30 male, 16 female), median age 73 years (IQR = 64–80), with an ICU stay of 6 days (range 4–11) were evaluated. CAM-ICU scores were obtained during 425 patient days. Considering the CAM-ICU as the reference standard, delirium occurred in 50% of the patients with a duration of 3 days (range 1–9). Days with delirium were poorly recognized by doctors (sensitivity 28.0%; specificity 100%) and ICU nurses (sensitivity 34.8%; specificity 98.3%). Recognition did not differ between hypoactive or active status of the patients involved.
Delirium is severely under recognized in the ICU by intensivists and ICU nurses in daily care. More attention should be paid to the implementation of a validated delirium-screening instrument during daily ICU care.
Electronic supplementary material
The online version of this article (doi:10.1007/s00134-009-1466-8) contains supplementary material, which is available to authorized users.
PMCID: PMC2698979  PMID: 19350214
Delirium; Critical care medicine; CAM-ICU; ICU; Recognition
11.  Increased liver stiffness denotes hepatic dysfunction and mortality risk in critically ill non-cirrhotic patients at a medical ICU 
Critical Care  2011;15(6):R266.
Hepatic dysfunction is a common finding in critically ill patients on the ICU and directly influences survival. Liver stiffness can be measured by the novel method of transient elastography (fibroscan) and is closely associated with hepatic fibrosis in patients with chronic liver disease, but also is increased in patients with acute hepatitis, acute liver failure and cholestasis. We investigated liver stiffness as a potentially useful tool for early detection of patients with hepatic deterioration and risk stratification with respect to short- and long-term mortality.
We prospectively evaluated 108 consecutive critically ill patients at our medical intensive care unit (ICU) with subsequent longitudinal liver stiffness measurements (admission, Day 3, Day 7 and weekly thereafter) during the course of ICU treatment. Outcome was followed after discharge (median observation time 237 days).
Liver stiffness could be reliably measured in 71% of ICU patients at admission (65% at Day 3, 63% at Day 7). Critically ill patients (n = 108) had significantly increased liver stiffness compared to sex- and age-matched standard care patients (n = 25). ICU patients with decompensated cirrhosis showed highest liver stiffness, whereas other critical diseases (for example, sepsis) and comorbidities (for example, diabetes, obesity) did not impact stiffness values. At admission to the ICU, liver stiffness is closely related to hepatic damage (liver synthesis, cholestasis, fibrosis markers). During the course of ICU treatment, fluid overload (renal failure, volume therapy) and increased central venous pressure (mechanical ventilation, heart failure) were major factors determining liver stiffness. Liver stiffness values > 18 kilopascal (kPa) at ICU admission were associated with increased ICU and long-term mortality, even in non-cirrhotic patients.
Considering that liver stiffness cannot be validly measured in about 30% of ICU patients, transient elastography performed at ICU admission might be a useful tool to early identify liver dysfunction and predict mortality in critically ill patients at a medical ICU.
PMCID: PMC3388655  PMID: 22082207
12.  Long-term outcomes and clinical predictors of hospital mortality in very long stay intensive care unit patients: a cohort study 
Critical Care  2006;10(2):R59.
Little information is available on prognosis and outcomes of very long stay intensive care unit (ICU) patients. The purpose of this study was to identify long-term outcomes after hospital discharge and readily available clinical predictors of hospital mortality for patients requiring prolonged care in the ICU.
Clinical data were collected from consecutive patients requiring at least 30 days of ICU care admitted over 3 calendar years (2001 to 2003) to a medical/surgical ICU in a university-affiliated tertiary care centre.
A total of 182 patients met the inclusion criteria, with a mean age of 63 years, median ICU stay of 48.5 days (interquartile range 36–78 days) and ICU mortality of 32%. They accounted for 8% of total admissions and 48% of total occupied beds. Of these patients, 42% died in hospital, 44% returned to their previous place of residence, and 14% were transferred to long-term care institutions. By 6 months after hospital discharge a further 8% of the patients had died, 40% remained at their previous place of residence, and 10% were in long-term care. Predictors of hospital mortality, identified using multivariate logistic regression, included age (odds ratio [OR] 1.45 per additional decade, 95% confidence interval [CI] 1.10–1.91), any immunosuppression (OR 5.2, 95% CI 1.7–15.5), mechanical ventilation for longer than 90 days (OR 4.0, 95% CI 1.3–12.0), treatment with inotropes or vasopressors for more than 3 days at or after day 30 in the ICU (OR 7.1, 95% CI 2.6–19.3), and acute renal failure requiring dialysis at or after day 30 in the ICU (OR 6.3, 95% CI 2.0–19.7).
Patients with very long stays in the ICU appear to have a reasonable chance of survival, with most survivors in our cohort residing at their previous place of residence 6 months after hospital discharge. Prolonged requirement for life support therapies (ventilation, vasoactive agents, or acute dialysis) and a limited number of pre-existing co-morbidities (immunosuppression and, to a lesser extent, patient age) were predictors of increased hospital mortality. These predictors may assist in clinical decision making for this resource intensive patient population, and their reproducibility in other very long stay patient populations should be explored.
PMCID: PMC1550909  PMID: 16606475
13.  Exercise rehabilitation for patients with critical illness: a randomized controlled trial with 12 months of follow-up 
Critical Care  2013;17(4):R156.
The purpose of this trial was to investigate the effectiveness of an exercise rehabilitation program commencing during ICU admission and continuing into the outpatient setting compared with usual care on physical function and health-related quality of life in ICU survivors.
We conducted a single-center, assessor-blinded, randomized controlled trial. One hundred and fifty participants were stratified and randomized to receive usual care or intervention if they were in the ICU for 5 days or more and had no permanent neurological insult. The intervention group received intensive exercises in the ICU and the ward and as outpatients. Participants were assessed at recruitment, ICU admission, hospital discharge and at 3-, 6- and 12-month follow-up. Physical function was evaluated using the Six-Minute Walk Test (6MWT) (primary outcome), the Timed Up and Go Test and the Physical Function in ICU Test. Patient-reported outcomes were measured using the Short Form 36 Health Survey, version 2 (SF-36v2) and Assessment of Quality of Life (AQoL) Instrument. Data were analyzed using mixed models.
The a priori enrollment goal was not reached. There were no between-group differences in demographic and hospital data, including acuity and length of acute hospital stay (LOS) (Acute Physiology and Chronic Health Evaluation II score: 21 vs 19; hospital LOS: 20 vs 24 days). No significant differences were found for the primary outcome of 6MWT or any other outcomes at 12 months after ICU discharge. However, exploratory analyses showed the rate of change over time and mean between-group differences in 6MWT from first assessment were greater in the intervention group.
Further research examining the trajectory of improvement with rehabilitation is warranted in this population.
Trial registration
The trial was registered with the Australian New Zealand Clinical Trials Registry ACTRN12605000776606.
PMCID: PMC4056792  PMID: 23883525
Critical illness; Exercise; Health-related quality of life; Physical function; Physiotherapy; Rehabilitation
14.  Intensive care unit acquired infection has no impact on long-term survival or quality of life: a prospective cohort study 
Critical Care  2007;11(2):R35.
The aim of this study was to evaluate the impact of intensive care unit (ICU)-acquired infection on long-term survival and quality of life.
Long-term survival was prospectively evaluated among hospital survivors who had stayed in a mixed, university-level ICU for longer than 48 hours during a 14-month study period during 2002 to 2003. Health-related quality of life was assessed using the five-dimensional EuroQol (EQ-5D) questionnaire in January 2005.
Of the 272 hospital survivors, 83 (30.5%) died after discharge during the follow-up period. The median follow-up time after hospital discharge was 22 months. Among patients without infection on admission, long-term mortality did not differ between patients who developed and those who did not develop an ICU-acquired infection (21.7% versus 26.9%; P = 0.41). Also, among patients with infection on admission, there was no difference in long-term mortality between patients who developed a superimposed (35.1%) and those who did not develop a superimposed (27.6%) ICU-acquired infection (P = 0.40). The EQ-5D response rate was 75 %. The patients who developed an ICU-acquired infection had significantly more problems with self-care (50%) than did those without an ICU-acquired infection (32%; P = 0.004), whereas multivariate analysis did not show ICU-acquired infection to be a significant risk factor for diminished self-care (odds ratio = 1.71, 95% confidence interval = 0.65–4.54; P = 0.28). General health status did not differ between those with and those without an ICU-acquired infection, as measured using the EuroQol visual-analogue scale (mean ± standard deviation EuroQol visual-analogue scale value: 60.2 ± 21 in patients without ICU-acquired infection versus 60.6 ± 22 in those with ICU-acquired infection). The current general level of health compared with status before ICU admission did not differ between the groups either. Only 36% of those employed resumed their previous jobs.
ICU-acquired infection had no impact on long-term survival. The patients with ICU-acquired infection more frequently experienced problems with self-care than did those without ICU infection, but ICU-acquired infection was not a significant risk factor for diminished self-care in multivariate analysis.
PMCID: PMC2206451  PMID: 17346355
15.  Days of Delirium Are Associated with 1-Year Mortality in an Older Intensive Care Unit Population 
Rationale: Delirium is a frequent occurrence in older intensive care unit (ICU) patients, but the importance of the duration of delirium in contributing to adverse long-term outcomes is unclear.
Objectives: To examine the association of the number of days of ICU delirium with mortality in an older patient population.
Methods: We performed a prospective cohort study in a 14-bed ICU in an urban acute care hospital. The patient population comprised 304 consecutive admissions 60 years of age and older.
Measurements and Main Results: The main outcome was 1-year mortality after ICU admission. Patients were assessed daily for delirium with the Confusion Assessment Method for the ICU and a validated chart review method. The median duration of ICU delirium was 3 days (range, 1–46 d). During the follow-up period, 153 (50%) patients died. After adjusting for relevant covariates, including age, severity of illness, comorbid conditions, psychoactive medication use, and baseline cognitive and functional status, the number of days of ICU delirium was significantly associated with time to death within 1 year post-ICU admission (hazard ratio, 1.10; 95% confidence interval, 1.02–1.18).
Conclusions: Number of days of ICU delirium was associated with higher 1-year mortality after adjustment for relevant covariates in an older ICU population. Investigations should be undertaken to reduce the number of days of ICU delirium and to study the impact of this reduction on important health outcomes, including mortality and functional and cognitive status.
PMCID: PMC2784414  PMID: 19745202
delirium; aging; mortality; intensive care
16.  Quality of life in patients aged 80 or over after ICU discharge 
Critical Care  2010;14(1):R2.
Our objective was to describe self-sufficiency and quality of life one year after intensive care unit (ICU) discharge of patients aged 80 years or over.
We performed a prospective observational study in a medical-surgical ICU in a tertiary non-university hospital. We included patients aged 80 or over at ICU admission in 2005 or 2006 and we recorded age, admission diagnosis, intensity of care, and severity of acute and chronic illnesses, as well as ICU, hospital, and one-year mortality rates. Self-sufficiency (Katz Index of Activities of Daily Living) was assessed at ICU admission and one year after ICU discharge. Quality of life (WHO-QOL OLD and WHO-QOL BREF) was assessed one year after ICU discharge.
Of the 115 consecutive patients aged 80 or over (18.2% of admitted patients), 106 were included. Mean age was 84 ± 3 years (range, 80 to 92). Mortality was 40/106 (37%) at ICU discharge, 48/106 (45.2%) at hospital discharge, and 73/106 (68.9%) one year after ICU discharge. In the 23 patients evaluated after one year, self-sufficiency was unchanged compared to the pre-admission status. Quality of life evaluations after one year showed that physical health, sensory abilities, self-sufficiency, and social participation had slightly worse ratings than the other domains, whereas social relationships, environment, and fear of death and dying had the best ratings. Compared to an age- and sex-matched sample of the general population, our cohort had better ratings for psychological health, social relationships, and environment, less fear of death and dying, better expectations about past, present, and future activities and better intimacy (friendship and love).
Among patients aged 80 or over who were selected at ICU admission, 80% were self-sufficient for activities of daily living one year after ICU discharge, 31% were alive, with no change in self-sufficiency and with similar quality of life to that of the general population matched on age and sex. However, these results must be interpreted cautiously due to the small sample of survivors.
PMCID: PMC2875504  PMID: 20064197
17.  Certainty and mortality prediction in critically ill children 
Journal of Medical Ethics  2004;30(3):304-307.
Objectives: The objective of this study is to investigate the relationship between a physician's subjective mortality prediction and the level of confidence with which that mortality prediction is made.
Design and participants: The study is a prospective cohort of patients less than 18 years of age admitted to a tertiary Paediatric Intensive Care Unit (ICU) at a University Children's Hospital with a minimum length of ICU stay of 10 h. Paediatric ICU attending physicians and fellows provided mortality risk predictions and the level of confidence associated with these predictions on consecutive patients at the time of multidisciplinary rounds within 24 hours of admission to the paediatric ICU. Median confidence levels were compared across different ranges of mortality risk predictions.
Results: Data were collected on 642 of 713 eligible patients (36 deaths, 5.6%). Mortality predictions greater than 5% and less than 95% were made with significantly less confidence than those predictions <5% and >95%. Experience was associated with greater confidence in prognostication.
Conclusions: We conclude that a physician's subjective mortality prediction may be dependent on the level of confidence in the prognosis; that is, a physician less confident in his or her prognosis is more likely to state an intermediate survival prediction. Measuring the level of confidence associated with mortality risk predictions (or any prognostic assessment) may therefore be important because different levels of confidence may translate into differences in a physician's therapeutic plans and their assessment of the patient's future.
PMCID: PMC1733866  PMID: 15173368
18.  Causes of death and determinants of outcome in critically ill patients 
Critical Care  2006;10(6):R154.
Whereas most studies focus on laboratory and clinical research, little is known about the causes of death and risk factors for death in critically ill patients.
Three thousand seven hundred patients admitted to an adult intensive care unit (ICU) were prospectively evaluated. Study endpoints were to evaluate causes of death and risk factors for death in the ICU, in the hospital after discharge from ICU, and within one year after ICU admission. Causes of death in the ICU were defined according to standard ICU practice, whereas deaths in the hospital and at one year were defined and grouped according to the ICD-10 (International Statistical Classification of Diseases and Related Health Problems) score. Stepwise logistic regression analyses were separately calculated to identify independent risk factors for death during the given time periods.
Acute, refractory multiple organ dysfunction syndrome was the most frequent cause of death in the ICU (47%), and central nervous system failure (relative risk [RR] 16.07, 95% confidence interval [CI] 8.3 to 31.4, p < 0.001) and cardiovascular failure (RR 11.83, 95% CI 5.2 to 27.1, p < 0.001) were the two most important risk factors for death in the ICU. Malignant tumour disease and exacerbation of chronic cardiovascular disease were the most frequent causes of death in the hospital (31.3% and 19.4%, respectively) and at one year (33.2% and 16.1%, respectively).
In this primarily surgical critically ill patient population, acute or chronic multiple organ dysfunction syndrome prevailed over single-organ failure or unexpected cardiac arrest as a cause of death in the ICU. Malignant tumour disease and chronic cardiovascular disease were the most important causes of death after ICU discharge.
PMCID: PMC1794454  PMID: 17083735
19.  Short- and long-term outcomes of HIV-infected patients admitted to the intensive care unit: impact of antiretroviral therapy and immunovirological status 
The purpose of this study was to assess the short- and long-term outcomes of HIV-infected patients admitted to intensive care units (ICU) according to immunovirological status at admission and highly active antiretroviral therapy (HAART) use in ICU.
Retrospective study of 98 HIV-infected patients hospitalized between 1997 and 2008 in two medical ICU in Montpellier, France. The primary outcome was mortality in ICU. The secondary end point was probability of survival in the year following ICU admission.
Eighty-two (83.6%) admissions in ICU were related to HIV infection and 45% of patients had received HAART before admission. Sixty-two patients (63.3%) were discharged from ICU, and 34 (34.7%) were alive at 1 year. Plasma HIV RNA viral load (VL) and CD4+ cell count separately were not associated with outcome. Independent predictors of ICU mortality were the use of vasopressive agents (odds ratio (OR), 3.779; 95% confidence interval (CI), 1.11–12.861; p = 0.0334) and SAPS II score (OR, 1.04; 95% CI, 1.003-1.077; p = 0.0319), whereas introducing or continuing HAART in ICU was protective (OR, 0.278; 95% CI, 0.082-0.939; p = 0.0393). Factors independently associated with 1-year mortality were immunovirological status with high VL (>3 log10/ml) and low CD4 (<200/mm3; hazard ratio (HR), 5.19; 95% CI, 1.328-20.279; p = 0.0179) or low VL (<3 log10/ml) and low CD4 (HR, 4.714; 95% CI, 1.178-18.867; p = 0.0284) vs. high CD4 and low VL, coinfection with C hepatitis virus (HR, 3.268; 95% CI, 1.29-8.278; p = 0.0125), the use of vasopressive agents (HR, 3.68; 95% CI, 1.394-9.716; p = 0.0085), and SAPS II score (HR, 1.09; 95% CI, 1.057-1.124; p <0.0001). Introducing HAART in a patient with no HAART at admission was associated with a better long-term outcome (HR, 0.166; 95% CI, 0.043-0.642; p = 0.0093).
In a population of HIV-infected patients admitted to ICU, short- and long-term outcomes are related to acute illness severity and immunovirological status at admission. Complementary studies are necessary to identify HIV-infected patients who benefit from HAART use in ICU according to immunovirological status and the reasons of ICU admission.
PMCID: PMC3465211  PMID: 22762133
Intensive care units; Human immunodeficiency virus; Acquired immunodeficiency syndrome; Antiretroviral therapy; Prognostic factors; Critical care; Mortality
20.  Vitamin D and Delirium in Critically Ill Patients: A Preliminary Investigation 
Journal of critical care  2012;28(3):230-235.
The pathophysiology of delirium in critical illness is unclear. 25-OH vitamin D (25-OHD) has neuroprotective properties but a relationship between serum 25-OHD and delirium has not been examined. We tested the hypothesis that low serum 25-OHD is associated with delirium during critical illness.
Materials and methods
In a prospective cohort of 120medical ICU patients, blood was collected within 24 hours of ICU admission for measurement of 25-OHD. Delirium was identified once daily using the Confusion Assessment Method for the ICU. Multivariable logistic regression was used to analyze the association between 25-OHD and delirium assessed the same day and the subsequent day after25-OHD measurement, with adjustments for age and severity of illness.
Median age was 52 years (IQR, 40, 62), and APACHE II was 23 (IQR, 17, 30). Thirty-seven patients (41%)were delirious on the day of 25-OHD measurement. 25-OHD levels were not associated with delirium on the day of 25-OHD measurement [OR 1.01, 95% CI: 0.98–1.02)] or on the day after measurement (OR 1.01, 95% CI:0.99–1.03).
This pilot study suggests that 25-OHD levels measured early during critical illness are not important determinants of delirium risk. Since 25-OHD levels can fluctuate during critical illness, a study of daily serial measurements of 25-OHD levels and their relationship to delirium during the duration of critical illness may yield different results.
PMCID: PMC3498519  PMID: 22884531
25-OH vitamin D; delirium; acute brain dysfunction; critical illness; intensive care unit
21.  Outcome of patients admitted during off hours in Moroccan intensive care unit 
The first few hours after intensive care unit (ICU) admission, where a patient’s condition is stabilized and treatment plans are formulated, are crucial to patient outcome. Although admission of patients who are unstable to ICU occurs 24 hours a day, not all units maintain the same level of staffing during off hours. We evaluated whether ICU admission during off hours affects mortality in a Moroccan ICU with the same level of staffing.
This prospective study was carried out at an ICU in a Moroccan hospital during 6 months. Demographic, clinic, acute physiology and chronic health evaluation score, length of stay, time of admission (day time or off hours), and ICU mortality data were collected. The mortality in the ICU was the end point of the study. Logistic regression analysis was used to identify risk factors associated with ICU mortality at various day and time of admission.
A total of 195 patients were included in the study; 125 (63.6%) were admitted during the day time and 70 (36.4%) were admitted during off hours. Most of the patients admitted during the off hours were male (75% versus 58% during the day time, P=0.01). Patients admitted in off hours after traumatism were more frequent than those admitted during the day time (64% versus 24%, P=0.001). There was no significant difference in ICU mortality for time of ICU admission (P=0.05).
We can conclude that off hours care is not necessarily inadequate. For ICU managers, it is important to know how to maintain adequate quality of care around the clock.
PMCID: PMC3942112  PMID: 24600244
intensive care unit; day time; off hours; mortality
22.  Survival Analysis of 314 Episodes of Sepsis in Medical Intensive Care Unit in University Hospital: Impact of Intensive Care Unit Performance and Antimicrobial Therapy 
Croatian medical journal  2006;47(3):385-397.
To evaluate epidemiology of sepsis in medical intensive care unit (ICU) in an university hospital, and the impact of ICU performance and appropriate empirical antibiotic therapy on survival of septic patients.
Observational, partly prospective study conducted over 6 years assessed all patients meeting the criteria for sepsis at ICU admission at the Sisters of Mercy Hospital in Zagreb. Clinical presentation of sepsis was defined according to 2001 International Sepsis Definitions Conference. Demographic data, admission category, source of infection, severity of sepsis, ICU or hospital stay and outcome, ICU performance, and appropriateness of empirical antibiotic therapy were analyzed.
The analysis included 314 of 5022 (6.3%) patients admitted to ICU during the study period. There were 176 (56.1%) ICU survivors. At the ICU admission, sepsis was present in 100 (31.8%), severe sepsis in 89 (28.6%), and septic shock in 125 (39.8%) patients with mortality rates 17%, 33.7%, 72.1%, respectively. During ICU treatment, 244 (77.7%) patients developed at least one organ dysfunction syndrome. Of 138 (43.9%) patients who met the criteria for septic shock, 107 (75.4) were non-survivors (P<0.001). Factors associated with in-ICU mortality were acquisition of sepsis at another department (odds ratio [OR] 0.06; 95% confidence interval [CI], 0.02-0.19), winter season (OR 0.42; 0.20-0.89), limited mobility (OR 0.28; 0.14-0.59), ICU length of stay (OR 0.82; 0.75-0.91), sepsis-related organ failure assessment (SOFA) score on day 1 (OR 0.80; 0.72-0.89), history of global heart failure (OR 0.33; 0.16-0.67), chronic obstructive pulmonary disease (COPD)-connected respiratory failure (OR 0.50; 0.27-0.93), septic shock present during ICU treatment (OR 0.03; 0.01-0.10), and negative blood culture at admission (OR 2.60; 0.81-6.23). Microbiological documentation of sepsis was obtained in 235 (74.8%) patients. Urinary tract infections were present in 168 (53.5%) patients, followed by skin or soft tissue infections in 58 (18.5%) and lower respiratory tract infections in 44 (14.0%) patients. Lower respiratory tract as focus of sepsis was connected with worse outcome (P<0.001). Empirical antibiotic treatment was considered adequate in 107 (60.8%) survivors and 42 (30.4%) non-survivors. Patients treated with adequate empirical antibiotic therapy had significantly higher survival time in hospital (log-rank, P = 0.001).
The mortality rate of sepsis was unacceptably high. The odds for poor outcome increased with acquisition of sepsis at another department, winter season, limited mobility, higher SOFA score on day 1, history of chronic global heart failure, COPD-connected respiratory failure, and septic shock present during ICU treatment, whereas longer ICU length of stay, positive blood culture, and adequate empirical antibiotic therapy were protective factors.
PMCID: PMC2080418  PMID: 16758516
23.  Impact of intensive care unit-acquired infection on hospital mortality in Japan: A multicenter cohort study 
To elucidate factors associated with hospital mortality in intensive care unit (ICU) patients and to evaluate the impact of ICU-acquired infection on hospital mortality in the context of the drug resistance of pathogens.
By using the Japanese Nosocomial Infection Surveillance (JANIS) database, 7,374 patients who were admitted to the 34 participating ICUs between July 2000 and May 2002, were aged 16 years or older, and who stayed in the ICU for 48 to 1,000 hours, did not transfer to another ICU, and did not become infected within 2 days after ICU admission, were followed up until hospital discharge or to Day 180 after ICU discharge. Adjusted hazard ratios (HRs) with the 95% confidence intervals (CIs) for hospital mortality were calculated using Cox’s proportional hazard model.
After adjusting for sex, age, and severity-of-illness (APACHE II score), a significantly higher HR for hospital mortality was found in ventilator use, central venous catheter use, and ICU-acquired drug-resistant infection, with a significantly lower HR in elective or urgent operations and urinary catheter use. The impact of ICU-acquired infection on hospital mortality was different between drug-susceptible pathogens (HR 1.11,95% CI:0.94–1.31) and drug-resistant pathogens (HR 1.42,95% CI: 1.15–1.77).
The use of a ventilator or a central venous catheter, and ICU-acquired drug-resistant infection were associated with a high risk of hospital mortality in ICU patients. The potential impact on hospital mortality emphasizes the importance of preventive measures against ICU-acquired infections, especially those caused by drug-resistant pathogens.
PMCID: PMC2723393  PMID: 21432299
multicenter cohort study; hospital mortality; ICU; nosocomial infection; drug resistance
24.  Mortality prediction using SAPS II: an update for French intensive care units 
Critical Care  2005;9(6):R645-R652.
The standardized mortality ratio (SMR) is commonly used for benchmarking intensive care units (ICUs). Available mortality prediction models are outdated and must be adapted to current populations of interest. The objective of this study was to improve the Simplified Acute Physiology Score (SAPS) II for mortality prediction in ICUs, thereby improving SMR estimates.
A retrospective data base study was conducted in patients hospitalized in 106 French ICUs between 1 January 1998 and 31 December 1999. A total of 77,490 evaluable admissions were split into a training set and a validation set. Calibration and discrimination were determined for the original SAPS II, a customized SAPS II and an expanded SAPS II developed in the training set by adding six admission variables: age, sex, length of pre-ICU hospital stay, patient location before ICU, clinical category and whether drug overdose was present. The training set was used for internal validation and the validation set for external validation.
With the original SAPS II calibration was poor, with marked underestimation of observed mortality, whereas discrimination was good (area under the receiver operating characteristic curve 0.858). Customization improved calibration but had poor uniformity of fit; discrimination was unchanged. The expanded SAPS II exhibited good calibration, good uniformity of fit and better discrimination (area under the receiver operating characteristic curve 0.879). The SMR in the validation set was 1.007 (confidence interval 0.985–1.028). Some ICUs had better and others worse performance with the expanded SAPS II than with the customized SAPS II.
The original SAPS II model did not perform sufficiently well to be useful for benchmarking in France. Customization improved the statistical qualities of the model but gave poor uniformity of fit. Adding simple variables to create an expanded SAPS II model led to better calibration, discrimination and uniformity of fit, producing a tool suitable for benchmarking.
PMCID: PMC1414016  PMID: 16280063
25.  Should highly active antiretroviral therapy be prescribed in critically ill HIV-infected patients during the ICU stay? A retrospective cohort study 
The impact of highly active antiretroviral therapy (HAART) in HIV-infected patients admitted to the intensive care unit (ICU) remains controversial. We evaluate impact of HAART prescription in HIV-infected patients admitted to the ICU of Tourcoing Hospital from January 2000 to December 2009.
There were 91 admissions concerning 85 HIV-infected patients. Reasons for ICU admission were an AIDS-related diagnosis in 46 cases (51%). Fifty two patients (57%) were on HAART at the time of ICU admission, leading to 21 immunovirologic successes (23%). During the ICU stay, HAART was continued in 29 patients (32%), and started in 3 patients (3%). Only one patient experienced an adverse event related to HAART. Mortality rate in ICU and 6 months after ICU admission were respectively 19% and 27%. Kaplan-Meier estimates of the cumulative unajusted survival probability over 6 months were higher in patients treated with HAART during the ICU stay (Log rank: p = 0.04). No benefit of HAART in ICU was seen in the adjusted survival proportion at 6 months or during ICU stay. Prescription of HAART during ICU was associated with a trend to lower incidence of new AIDS-related events at 6 months (respectively 17% and 34% with and without HAART, p = 0.07), and with higher incidence of antiretroviral resistance after ICU stay (respectively 25% and 7% with and without HAART, p = 0.02).
Our results suggest a lower death rate over 6 months in critically ill HIV-infected patients taking HAART during ICU stay. The optimal time to prescribe HAART in critically ill patients needs to be better defined.
PMCID: PMC3544704  PMID: 23020962
HIV; Intensive care; HAART

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