Is it worth treating fever in intensive care unit patients? Preliminary results from a randomized trial of the effect of external cooling.

BACKGROUND: Antipyresis is a common clinical practice in intensive care, although it is unknown if fever is harmful, beneficial, or a negligible adverse effect of infection and inflammation. METHODS: In a randomized study, rectal temperature and discomfort were assessed in 38 surgical intensive care unit patients without neurotrauma or severe hypoxemia and with fever (temperature >/=38.5 degrees C) and systemic inflammatory response syndrome. Eighteen patients received external cooling while 20 received no antipyretic treatment. RESULTS: Temperature and discomfort decreased similarly in both groups after 24 hours. No significant differences in recurrence of fever, incidence of infection, antibiotic therapy, intensive care unit and hospital length of stay, or mortality were noted between the groups. CONCLUSIONS: These results suggest that the systematic suppression of fever may not be useful in patients without severe cranial trauma or significant hypoxemia. Letting fever take its natural course does not seem to harm patients with systemic inflammatory response syndrome or influence the discomfort level and may save costs.

Candida bloodstream infections in intensive care units: analysis of the extended prevalence of infection in intensive care unit study.

OBJECTIVES: To provide a global, up-to-date picture of the prevalence, treatment, and outcomes of Candida bloodstream infections in intensive care unit patients and compare Candida with bacterial bloodstream infection. DESIGN: A retrospective analysis of the Extended Prevalence of Infection in the ICU Study (EPIC II). Demographic, physiological, infection-related and therapeutic data were collected. Patients were grouped as having Candida, Gram-positive, Gram-negative, and combined Candida/bacterial bloodstream infection. Outcome data were assessed at intensive care unit and hospital discharge. SETTING: EPIC II included 1265 intensive care units in 76 countries. PATIENTS: Patients in participating intensive care units on study day. INTERVENTIONS: None. MEASUREMENT AND MAIN RESULTS: Of the 14,414 patients in EPIC II, 99 patients had Candida bloodstream infections for a prevalence of 6.9 per 1000 patients. Sixty-one patients had candidemia alone and 38 patients had combined bloodstream infections. Candida albicans (n = 70) was the predominant species. Primary therapy included monotherapy with fluconazole (n = 39), caspofungin (n = 16), and a polyene-based product (n = 12). Combination therapy was infrequently used (n = 10). Compared with patients with Gram-positive (n = 420) and Gram-negative (n = 264) bloodstream infections, patients with candidemia were more likely to have solid tumors (p < .05) and appeared to have been in an intensive care unit longer (14 days [range, 5-25 days], 8 days [range, 3-20 days], and 10 days [range, 2-23 days], respectively), but this difference was not statistically significant. Severity of illness and organ dysfunction scores were similar between groups. Patients with Candida bloodstream infections, compared with patients with Gram-positive and Gram-negative bloodstream infections, had the greatest crude intensive care unit mortality rates (42.6%, 25.3%, and 29.1%, respectively) and longer intensive care unit lengths of stay (median [interquartile range]) (33 days [18-44], 20 days [9-43], and 21 days [8-46], respectively); however, these differences were not statistically significant. CONCLUSION: Candidemia remains a significant problem in intensive care units patients. In the EPIC II population, Candida albicans was the most common organism and fluconazole remained the predominant antifungal agent used. Candida bloodstream infections are associated with high intensive care unit and hospital mortality rates and resource use.

Continuous electroencephalographic monitoring in critically ill patients with central nervous system infections.

OBJECTIVES: To determine the prevalence, predictors, and clinical significance of electrographic seizures (ESz) and other continuous electroencephalographic monitoring findings in critically ill patients with central nervous system infections. DESIGN: Retrospective cohort study. SETTING: Eighteen-bed neurocritical care unit. PATIENTS: We identified 42 consecutive patients with primary central nervous system infection (viral, 27 patients [64%]; bacterial, 8 patients [18%]; and fungal or parasitic, 7 patients [17%]) who underwent continuous electroencephalographic monitoring between January 1, 1996, and February 28, 2007. MAIN OUTCOME MEASURES: Presence of ESz or periodic epileptiform discharges (PEDs). RESULTS: Electrographic seizures were recorded in 14 patients (33%), and PEDs were recorded in 17 patients (40%). Twenty patients (48%) had either PEDs or ESz. Of the 14 patients with ESz, only 5 (36%) had a clinical correlate. Periodic epileptiform discharges (odds ratio=13.4; P=.001) and viral cause (odds ratio=13.0; P=.02) were independently associated with ESz. Both ESz (odds ratio=5.9; P=.02) and PEDs (odds ratio=6.1; P=.01) were independently associated with poor outcome at discharge (severe disability, vegetative state, or death). CONCLUSIONS: In patients with central nervous system infections undergoing continuous electroencephalographic monitoring, ESz and/or PEDs were frequent, occurring in 48% of our cohort. More than half of the ESz had no clinical correlate. Both ESz and PEDs were independently associated with poor outcome. Additional studies are needed to determine whether prevention or treatment of these electrographic findings improves outcome.

A satisfaction survey conducted on patients of a medico-legal consultation.

In 2006, a medico-legal consultation service devoted to adult victims of interpersonal violence was set up at the Lausanne University Hospital Centre, Switzerland: the Violence Medical Unit. Patients are received by forensic nurses for support, forensic examination (in order to establish medical report) and community orientation. In 2008, a telephone survey was conducted on patients. The objectives of the survey were to estimate the degree of patients' satisfaction and to document the use of the medical report by six questions. Among the 476 patients admitted to the VMU in 2007, 132 were interviewed. Their overall satisfaction was high with an average mark of 8.7/10. The medical report was used extensively by the interviewed victims (81%) for its primary function - to be produced as evidence. As the consultations are financed by public funds, these results were of interest for advocacy of long-lasting financial support.

Stress ulcer prophylaxis in non-critically ill patients: a prospective evaluation of current practice in a general surgery department.

RATIONALE, AIMS AND OBJECTIVES: There is little evidence regarding the benefit of stress ulcer prophylaxis (SUP) outside a critical care setting. Overprescription of SUP is not devoid of risks. This prospective study aimed to evaluate the use of proton pump inhibitors (PPIs) for SUP in a general surgery department. METHOD: Data collection was performed prospectively during an 8-week period on patients hospitalized in a general surgery department (58 beds) by pharmacists. Patients with a PPI prescription for the treatment of ulcers, gastro-oesophageal reflux disease, oesophagitis or epigastric pain were excluded. Patients admitted twice during the study period were not reincluded. The American Society of Health-System Pharmacists guidelines on SUP were used to assess the appropriateness of de novo PPI prescriptions. RESULTS: Among 255 patients in the study, 138 (54%) received a prophylaxis with PPI, of which 86 (62%) were de novo PPI prescriptions. A total of 129 patients (94%) received esomeprazole (according to the hospital drug policy). The most frequent dosage was at 40 mg once daily. Use of PPI for SUP was evaluated in 67 patients. A total of 53 patients (79%) had no risk factors for SUP. Twelve and two patients had one or two risk factors, respectively. At discharge, PPI prophylaxis was continued in 33% of patients with a de novo PPI prescription. CONCLUSIONS: This study highlights the overuse of PPIs in non-intensive care unit patients and the inappropriate continuation of PPI prescriptions at discharge. Treatment recommendations for SUP are needed to restrict PPI use for justified indications.

Validation of the spiritual distress assessment tool in older hospitalized patients.

ABSTRACT:¦BACKGROUND: The Spiritual Distress Assessment Tool (SDAT) is a 5-item instrument developed to assess unmet spiritual needs in hospitalized elderly patients and to determine the presence of spiritual distress. The objective of this study was to investigate the SDAT psychometric properties.¦METHODS: This cross-sectional study was performed in a Geriatric Rehabilitation Unit. Patients (N = 203), aged 65 years and over with Mini Mental State Exam score ≥ 20, were consecutively enrolled over a 6-month period. Data on health, functional, cognitive, affective and spiritual status were collected upon admission. Interviews using the SDAT (score from 0 to 15, higher scores indicating higher distress) were conducted by a trained chaplain. Factor analysis, measures of internal consistency (inter-item and item-to-total correlations, Cronbach α), and reliability (intra-rater and inter-rater) were performed. Criterion-related validity was assessed using the Functional Assessment of Chronic Illness Therapy-Spiritual well-being (FACIT-Sp) and the question "Are you at peace?" as criterion-standard. Concurrent and predictive validity were assessed using the Geriatric Depression Scale (GDS), occurrence of a family meeting, hospital length of stay (LOS) and destination at discharge.¦RESULTS: SDAT scores ranged from 1 to 11 (mean 5.6 ± 2.4). Overall, 65.0% (132/203) of the patients reported some spiritual distress on SDAT total score and 22.2% (45/203) reported at least one severe unmet spiritual need. A two-factor solution explained 60% of the variance. Inter-item correlations ranged from 0.11 to 0.41 (eight out of ten with P < 0.05). Item-to-total correlations ranged from 0.57 to 0.66 (all P < 0.001). Cronbach α was acceptable (0.60). Intra-rater and inter-rater reliabilities were high (Intraclass Correlation Coefficients ranging from 0.87 to 0.96). SDAT correlated significantly with the FACIT-Sp, "Are you at peace?", GDS (Rho -0.45, -0.33, and 0.43, respectively, all P < .001), and LOS (Rho 0.15, P = .03). Compared with patients showing no severely unmet spiritual need, patients with at least one severe unmet spiritual need had higher odds of occurrence of a family meeting (adjOR 4.7, 95%CI 1.4-16.3, P = .02) and were more often discharged to a nursing home (13.3% vs 3.8%; P = .027).¦CONCLUSIONS: SDAT has acceptable psychometrics properties and appears to be a valid and reliable instrument to assess spiritual distress in elderly hospitalized patients.

Computed tomography angiography vs 3 T black-blood cardiovascular magnetic resonance for identification of symptomatic carotid plaques.

BACKGROUND: The purpose of this prospective study was to perform a head-to-head comparison of the two methods most frequently used for evaluation of carotid plaque characteristics: Multi-detector Computed Tomography Angiography (MDCTA) and black-blood 3 T-cardiovascular magnetic resonance (bb-CMR) with respect to their ability to identify symptomatic carotid plaques. METHODS: 22 stroke unit patients with unilateral symptomatic carotid disease and >50% stenosis by duplex ultrasound underwent MDCTA and bb-CMR (TOF, pre- and post-contrast fsT1w-, and fsT2w- sequences) within 15 days of symptom onset. Both symptomatic and contralateral asymptomatic sides were evaluated. By bb-CMR, plaque morphology, composition and prevalence of complicated AHA type VI lesions (AHA-LT6) were evaluated. By MDCTA, plaque type (non-calcified, mixed, calcified), plaque density in HU and presence of ulceration and/or thrombus were evaluated. Sensitivity (SE), specificity (SP), positive and negative predictive value (PPV, NPV) were calculated using a 2-by-2-table. RESULTS: To distinguish between symptomatic and asymptomatic plaques AHA-LT6 was the best CMR variable and presence / absence of plaque ulceration was the best CT variable, resulting in a SE, SP, PPV and NPV of 80%, 80%, 80% and 80% for AHA-LT6 as assessed by bb-CMR and 40%, 95%, 89% and 61% for plaque ulceration as assessed by MDCTA. The combined SE, SP, PPV and NPV of bb-CMR and MDCTA was 85%, 75%, 77% and 83%, respectively. CONCLUSIONS: Bb-CMR is superior to MDCTA at identifying symptomatic carotid plaques, while MDCTA offers high specificity at the cost of low sensitivity. Results were only slightly improved over bb-CMR alone when combining both techniques.

Glucose control after severe brain injury.

PURPOSE OF REVIEW: A substantial body of evidence supports the use of intensive insulin therapy in general critical care practice, particularly in surgical intensive care unit patients. The impact of intensive insulin therapy on the outcome of critically ill neurological patients, however, is still controversial. While avoidance of hyperglycemia is recommended in neurointensive care, no recommendations exist regarding the optimal target for systemic glucose control after severe brain injury. RECENT FINDINGS: An increase in brain metabolic demand leading to a deficiency in cerebral extracellular glucose has been observed in critically ill neurological patients and correlates with poor outcome. In this setting, a reduction of systemic glucose below 6 mmol/l with exogenous insulin has been found to exacerbate brain metabolic distress. Recent studies have confirmed these findings while showing intensive insulin therapy to have no substantial benefit on the outcome of critically ill neurological patients. SUMMARY: Questions persist regarding the optimal target for glucose control after severe brain injury. Further studies are needed to analyze the impact of intensive insulin therapy on brain glucose metabolism and outcome of critically ill neurological patients. According to the available evidence, a less restrictive target for systemic glucose control (6-10 mmol/l) may be more appropriate.

Genetic Polymorphisms and Susceptibility to Fungal Infections

Invasive fungal infections (IFI) are life-threatening diseases that are of particular concern in specific debilitated or immunosuppressed populations. Invasive candidiasis (IC) is the most frequent of the IFI, being one of the major causes of nosocomial bloodstream infection and a feared complication in patients with recurrent gastrointestinal surgery or prolonged stay in the intensive-care unit [1,2]. Patients with hematological malignancies or prolonged chemotherapy-induced neutropenia, and those with allogeneic hematopoietic stem cell transplantation (allo-HSCT), represent the groups at highest risk for developing invasive aspergillosis (IA), which is associated with a high mortality rate despite the increasing availability of antifungal therapies [3,4]. An increasing incidence of IA has also been reported in non-neutropenic immunosuppressed populations such as solid-organ transplant recipients or steroid-treated patients with chronic pulmonary diseases [5]. Early diagnosis of IFI is crucial for improving chances of survival [6], but is particularly challenging owing to the lack of reliable diagnostic methods [7,8]. Significant efforts during the last few decades have focused on the prevention of these severe complications. Antifungal prophylaxis in high-risk patients has been shown to reduce the incidence of IA in patients with onco-hematological malignancies [9] and that of IC in surgical intensive-care unit patients [10]. However, its widespread use raises concerns about costs, toxicity, and the risk of emergence of resistant fungal species such as non-Aspergillus moulds or non-albicansCandida spp. [4,11,12]. Prophylactic strategies usually rely on the identification of host risk factors resulting from clinical conditions (type and duration of immunosuppression, underlying diseases, and extrinsic interventions) [8,13]. Recent advances in the field of immunogenetics may change our perspective of, and approach to, preventive strategies with the identification of subgroups of patients exhibiting a genetic predisposition to IFI.

Pancreatic stone protein as a postmortem biochemical marker for the diagnosis of sepsis.

Pancreatic stone protein/regenerating protein has recently emerged as an interesting diagnostic and prognostic marker of inflammation and sepsis in the clinical field. Increased blood concentrations have been described in patients with sepsis. Moreover, a high accuracy in predicting fatal outcomes in septic patients admitted to intensive care units has been reported. In this study, we investigated pancreatic stone protein/regenerating protein in postmortem serum in a series of sepsis-related fatalities, local infections and non-infectious cases that underwent medico-legal investigations. Procalcitonin, C-reactive protein, interleukin 6, soluble triggering receptor expressed on myeloid cells-1 and pancreatic stone protein/regenerating protein were measured in the postmortem serum collected during autopsy in a group of sepsis-related deaths, local infections and non-septic intensive care unit patients. Statistically significant differences in pancreatic stone protein/regenerating protein concentrations were observed between sepsis and control patients. A significant positive correlation was found between procalcitonin and pancreatic stone protein/regenerating protein values in septic cases. Pancreatic stone protein/regenerating protein is measurable in postmortem serum from femoral blood collected during autopsy. Additionally, as in the clinical field, pancreatic stone protein/regenerating protein can be used as a postmortem biochemical marker for the diagnosis of sepsis.

Impact of tight glycemic control on cerebral glucose metabolism after severe brain injury: a microdialysis study.

OBJECTIVES: To analyze the effect of tight glycemic control with the use of intensive insulin therapy on cerebral glucose metabolism in patients with severe brain injury. DESIGN: Retrospective analysis of a prospective observational cohort. SETTING: University hospital neurologic intensive care unit. PATIENTS: Twenty patients (median age 59 yrs) monitored with cerebral microdialysis as part of their clinical care. INTERVENTIONS: Intensive insulin therapy (systemic glucose target: 4.4-6.7 mmol/L [80-120 mg/dL]). MEASUREMENTS AND MAIN RESULTS: Brain tissue markers of glucose metabolism (cerebral microdialysis glucose and lactate/pyruvate ratio) and systemic glucose were collected hourly. Systemic glucose levels were categorized as within the target "tight" (4.4-6.7 mmol/L [80-120 mg/dL]) vs. "intermediate" (6.8-10.0 mmol/L [121-180 mg/dL]) range. Brain energy crisis was defined as a cerebral microdialysis glucose <0.7 mmol/L with a lactate/pyruvate ratio >40. We analyzed 2131 cerebral microdialysis samples: tight systemic glucose levels were associated with a greater prevalence of low cerebral microdialysis glucose (65% vs. 36%, p < 0.01) and brain energy crisis (25% vs.17%, p < 0.01) than intermediate levels. Using multivariable analysis, and adjusting for intracranial pressure and cerebral perfusion pressure, systemic glucose concentration (adjusted odds ratio 1.23, 95% confidence interval [CI] 1.10-1.37, for each 1 mmol/L decrease, p < 0.001) and insulin dose (adjusted odds ratio 1.10, 95% CI 1.04-1.17, for each 1 U/hr increase, p = 0.02) independently predicted brain energy crisis. Cerebral microdialysis glucose was lower in nonsurvivors than in survivors (0.46 +/- 0.23 vs. 1.04 +/- 0.56 mmol/L, p < 0.05). Brain energy crisis was associated with increased mortality at hospital discharge (adjusted odds ratio 7.36, 95% CI 1.37-39.51, p = 0.02). CONCLUSIONS: In patients with severe brain injury, tight systemic glucose control is associated with reduced cerebral extracellular glucose availability and increased prevalence of brain energy crisis, which in turn correlates with increased mortality. Intensive insulin therapy may impair cerebral glucose metabolism after severe brain injury.

A Randomized, Placebo-controlled Trial of Preemptive Antifungal Therapy for the Prevention of Invasive Candidiasis Following Gastrointestinal Surgery for Intra-abdominal Infections.

BACKGROUND: Patients undergoing emergency gastrointestinal surgery for intra-abdominal infection are at risk of invasive candidiasis (IC) and candidates for preemptive antifungal therapy. METHODS: This exploratory, randomized, double-blind, placebo-controlled trial assessed a preemptive antifungal approach with micafungin (100 mg/d) in intensive care unit patients requiring surgery for intra-abdominal infection. Coprimary efficacy variables were the incidence of IC and the time from baseline to first IC in the full analysis set; an independent data review board confirmed IC. An exploratory biomarker analysis was performed using logistic regression. RESULTS: The full analysis set comprised 124 placebo- and 117 micafungin-treated patients. The incidence of IC was 8.9% for placebo and 11.1% for micafungin (difference, 2.24%; [95% confidence interval, -5.52 to 10.20]). There was no difference between the arms in median time to IC. The estimated odds ratio showed that patients with a positive (1,3)-β-d-glucan (ßDG) result were 3.66 (95% confidence interval, 1.01-13.29) times more likely to have confirmed IC than those with a negative result. CONCLUSIONS: This study was unable to provide evidence that preemptive administration of an echinocandin was effective in preventing IC in high-risk surgical intensive care unit patients with intra-abdominal infections. This may have been because the drug was administered too late to prevent IC coupled with an overall low number of IC events. It does provide some support for using ßDG to identify patients at high risk of IC. CLINICAL TRIALS REGISTRATION: NCT01122368.

Delay for admission of unstable hospitalized patients to intensive care unit: a need for a medical emergency team?

INTRODUCTION. Patients admitted in Intensive Care Unit (ICU) from general wards are more severe and have a higher mortality than those admitted from emergency department as reported [1]. The majority of them develop signs of instability (e.g. tachypnea, tachycardia, hypotension, decreased oxygen saturation and change in conscious state) several hours before ICU admission. Considering this fact and that in-hospital cardiac arrests and unexpected deaths are usually preceded by warning signs, immediate on site intervention by specialists may be effective. This gave an impulse to medical emergency team (MET) implementation, which has been shown to decrease cardiac arrest, morbidity and mortality in several hospitals. OBJECTIVES AND METHODS. In order to verify if the same was true in our hospital and to determine if there was a need for MET, we prospectively collected all non elective ICU admissions of already hospitalized patients (general wards) and of patients remaining more than 3 h in emergency department (considered hospitalized). Instability criteria leading to MET call correspond to those described in the literature. The delay between the development of one criterion and ICU admission was registered. RESULTS. During an observation period of 12 months, 321 patients with our MET criteria were admitted to ICU. 88 patients came from the emergency department, 115 from the surgical and 113 from the medical ward. 65% were male. The median age was 65 years (range 17-89). The delay fromMETcriteria development to ICU admission was higher than 8 h in 155 patients, with a median delay of 32 h and a range of 8.4 h to 10 days. For the remaining 166 patients, an early MET criterion was present up to 8 h (median delay 3 h) before ICU admission. These results are quite concordant with the data reported in the literature (ref 1-8). 122 patients presented signs of sepsis or septic shock, 70 patients a respiratory failure, 58 patients a cardiac emergency. Cardiac arrest represent 5% of our collective of patients. CONCLUSIONS.Similar to others observations, the majority of hospitalized patients admitted on emergency basis in our ICU have warning signs lasting for several hours. More than half of them were unstable for more than 8 h. This shows there is plenty of time for early acute management by dedicated and specialized team such as MET. However, further studies are required to determine if MET implementation can reduce in-hospital cardiac arrests and influence the morbidity, the length of stay and the mortality.

Prospective monitoring of cefepime in intensive care unit adult patients

Rapport de synthèse :Le céfépime a été associé à un taux de mortalité supérieur à celui des autres bêta-lactamines chez les patients traités pour un sepsis sévère. Une des hypothèses avancées pour expliquer ces échecs thérapeutiques sont de possibles effets secondaires cachés (par ex. neurologiques) ou des paramètres pharmacocinétiques/pharmacodynamiques (PK/PD) inadaptés. Le présent travail a étudié cette problématique en mesurant prospectivement la pharmacocinétique du céfépime chez 21 patients consécutifs hospitalisés aux soins intensifs adultes (SIAD) pour une pneumonie nosocomiale. La population étudiée avec un âge médian 55,1 ans, a reçu par voie intraveineuse du céfépime à raison de 2 g toutes les 12 heures pour une clairance de la créatinine (Clcr)>50 mI/ min, et 2 g toutes les 24 heures ou 36 heures pour une Clcr<50 ml /min. Les taux plasmatiques de céfépime ont été mesurés à plusieurs reprises avant et après administration du médicament après la lèoe dose et à l'état d'équilibre par chromatographie en phase liquide à haute pression. Les taux plasmatiques ont considérablement varié entre les patients. Cent pour cent (21/21) des patients ont eu une durée appropriée d'antibiothérapie avec des taux plasmatiques supérieures à la CMI du céfépime (T>CMI>50%) pour les agents pathogènes retrouvés dans cette étude (CMI<4 mg/I), mais seulement 45-65% d'entre eux ont eu une couverture appropriée pour les agents pathogènes potentiels présentant une CMI> 8 mg/I pour le céfépime. Deux patients avec une insuffisance rénale (Clcr<30 ml/min) ont présenté des symptômes compatibles avec une épilepsie non-convulsive (état confusionnel et myoclonies) attribuée dans un 2ème temps à une toxicité du céfépime après que les taux plasmatiques aient été communiqués aux soignants qui ont suspendu l'antibiothérapie avec disparition des symptômes. Les résultats de cette étude empirique confirment l'existence d'effets secondaires cachés et de paramètres PK/PD inappropriés (pour les agents pathogènes ayant des CMI de limite supérieure) dans notre population de SIAD. En outre, ils mettent en évidence une fenêtre thérapeutique efficace pour une posologie de céfépime de 2 g toutes les 12 heures chez les patients ayant une Clcr>50 ml/min infectés par des pathogènes avec des CMI pour le céfépime <4 mg/I. Les échecs thérapeutiques constatés dans cette étude sont probablement liés à des taux sériques inadaptés, résultant de la difficulté de prescription dans les situations cliniques complexes. Dans ce contexte, un prompt dosage plasmatique du céfépime doit être considéré en cas de diminution de la Clcr ou en présence de CMI élevées.