Potential Cost-effectiveness of Early Identification of Hospital-acquired Infection in Critically Ill Patients.

RATIONALE: Limitations in methods for the rapid diagnosis of hospital-acquired infections often delay initiation of effective antimicrobial therapy. New diagnostic approaches offer potential clinical and cost-related improvements in the management of these infections. OBJECTIVES: We developed a decision modeling framework to assess the potential cost-effectiveness of a rapid biomarker assay to identify hospital-acquired infection in high-risk patients earlier than standard diagnostic testing. METHODS: The framework includes parameters representing rates of infection, rates of delayed appropriate therapy, and impact of delayed therapy on mortality, along with assumptions about diagnostic test characteristics and their impact on delayed therapy and length of stay. Parameter estimates were based on contemporary, published studies and supplemented with data from a four-site, observational, clinical study. Extensive sensitivity analyses were performed. The base-case analysis assumed 17.6% of ventilated patients and 11.2% of nonventilated patients develop hospital-acquired infection and that 28.7% of patients with hospital-acquired infection experience delays in appropriate antibiotic therapy with standard care. We assumed this percentage decreased by 50% (to 14.4%) among patients with true-positive results and increased by 50% (to 43.1%) among patients with false-negative results using a hypothetical biomarker assay. Cost of testing was set at $110/d. MEASUREMENTS AND MAIN RESULTS: In the base-case analysis, among ventilated patients, daily diagnostic testing starting on admission reduced inpatient mortality from 12.3 to 11.9% and increased mean costs by $1,640 per patient, resulting in an incremental cost-effectiveness ratio of $21,389 per life-year saved. Among nonventilated patients, inpatient mortality decreased from 7.3 to 7.1% and costs increased by $1,381 with diagnostic testing. The resulting incremental cost-effectiveness ratio was $42,325 per life-year saved. Threshold analyses revealed the probabilities of developing hospital-acquired infection in ventilated and nonventilated patients could be as low as 8.4 and 9.8%, respectively, to maintain incremental cost-effectiveness ratios less than $50,000 per life-year saved. CONCLUSIONS: Development and use of serial diagnostic testing that reduces the proportion of patients with delays in appropriate antibiotic therapy for hospital-acquired infections could reduce inpatient mortality. The model presented here offers a cost-effectiveness framework for future test development.

Effect of intravenous haloperidol on the duration of delirium and coma in critically ill patients (Hope-ICU):A randomised, double-blind, placebo-controlled trial

Background: Delirium is frequently diagnosed in critically ill patients and is associated with poor clinical outcomes. Haloperidol is the most commonly used drug for delirium despite little evidence of its effectiveness. The aim of this study was to establish whether early treatment with haloperidol would decrease the time that survivors of critical illness spent in delirium or coma. Methods: We did this double-blind, placebo-controlled randomised trial in a general adult intensive care unit (ICU). Critically ill patients (≥18 years) needing mechanical ventilation within 72 h of admission were enrolled. Patients were randomised (by an independent nurse, in 1:1 ratio, with permuted block size of four and six, using a centralised, secure web-based randomisation service) to receive haloperidol 2·5 mg or 0·9% saline placebo intravenously every 8 h, irrespective of coma or delirium status. Study drug was discontinued on ICU discharge, once delirium-free and coma-free for 2 consecutive days, or after a maximum of 14 days of treatment, whichever came first. Delirium was assessed using the confusion assessment method for the ICU (CAM-ICU). The primary outcome was delirium-free and coma-free days, defined as the number of days in the first 14 days after randomisation during which the patient was alive without delirium and not in coma from any cause. Patients who died within the 14 day study period were recorded as having 0 days free of delirium and coma. ICU clinical and research staff and patients were masked to treatment throughout the study. Analyses were by intention to treat. This trial is registered with the International Standard Randomised Controlled Trial Registry, number ISRCTN83567338. Findings: 142 patients were randomised, 141 were included in the final analysis (71 haloperidol, 70 placebo). Patients in the haloperidol group spent about the same number of days alive, without delirium, and without coma as did patients in the placebo group (median 5 days [IQR 0-10] vs 6 days [0-11] days; p=0·53). The most common adverse events were oversedation (11 patients in the haloperidol group vs six in the placebo group) and QTc prolongation (seven patients in the haloperidol group vs six in the placebo group). No patient had a serious adverse event related to the study drug. Interpretation: These results do not support the hypothesis that haloperidol modifies duration of delirium in critically ill patients. Although haloperidol can be used safely in this population of patients, pending the results of trials in progress, the use of intravenous haloperidol should be reserved for short-term management of acute agitation. Funding: National Institute for Health Research. © 2013 Elsevier Ltd.

Responsiveness of the frontal EMG for monitoring the sedation state of critically ill patients.

Background. Excessive sedation is associated with adverse patient outcomes during critical illness, and a validated monitoring technology could improve care. We developed a novel method, the responsiveness index (RI) of the frontal EMG. We compared RI data with Ramsay clinical sedation assessments in general and cardiac intensive care unit (ICU) patients. Methods. We developed the algorithm by iterative analysis of detailed observational data in 30 medical–surgical ICU patients and described its performance in this cohort and 15 patients recovering from scheduled cardiac surgery. Continuous EMG data were collected via frontal electrodes and RI data compared with modified Ramsay sedation state assessments recorded regularly by a blinded trained observer. RI performance was compared with EntropyTM across Ramsay categories to assess validity. Results. RI correlated well with the Ramsay category, especially for the cardiac surgery cohort (general ICU patients r¼0.55; cardiac surgery patients r¼0.85, both P,0.0001). Discrimination across all Ramsay categories was reasonable in the general ICU patient cohort [PK¼0.74 (SEM 0.02)] and excellent in the cardiac surgery cohort [PK¼0.92 (0.02)]. Discrimination between ‘lighter’ vs ‘deeper’ (Ramsay 1–3 vs 4–6) was good for general ICU patients [PK¼0.80 (0.02)] and excellent for cardiac surgery patients [PK¼0.96 (0.02)]. Performance was significantly better than EntropyTM. Examination of individual cases suggested good face validity. Conclusions. RI of the frontal EMG has promise as a continuous sedation state monitor in critically ill patients. Further investigation to determine its utility in ICU decision-making is warranted.

Epidemiology of invasive aspergillosis in critically ill patients: clinical presentation, underlying conditions, and outcomes

INTRODUCTION: Invasive aspergillosis (IA) is a fungal infection that particularly affects immunocompromised hosts. Recently, several studies have indicated a high incidence of IA in intensive care unit (ICU) patients. However, few data are available on the epidemiology and outcome of patients with IA in this setting.

Experiences of health professionals with nutritional support of critically ill patients in tertiary hospitals in Malawi

Background Nutritional support is a recognized determinant of outcome in critically ill patients. Development of critical care services in low-income countries has not been accompanied by certain appropriate ancillary services and interventions, such as adequate nutritional support. This study was designed to investigate the experiences of health professionals who have provided nutritional supportive care to critically ill patients admitted to two major central hospitals in Malawi, with the aim of identifying the common practices in nutritional support in these settings. Materials and Methods A cross-sectional study in which 50 health professionals working in intensive care and high dependency units, admitting both adult and pediatric patients, were interviewed using a semi-structured questionnaire. Data were coded and then analyzed using SPSS version 16.0. Responses between the two hospitals were compared using Fisher’s exact test. Results There was no difference in the composition of respondents from the two hospitals. About 60% of respondents had had experience with nutritional supplementation in their patients—mainly enteral. The most commonly used formulations were the “ready-to-use therapeutic feeds,” followed by modified milk. A high percentage of respondents (40%) reported having used dextrose solution as the sole nutritional supplement. Lack of in-service training, nonexistent nutrition protocols pertaining to acutely and critically ill patients, and a lack of clinical nutritionists were the major challenges identified. Conclusion Knowledge of nutrient supplementation was poor among the respondents. The use of ready-to-use therapeutic feeds was quite common, although there is no evidence of its effectiveness in care of acutely critically ill patients. There is a need to establish nutritional support teams in these tertiary hospitals. Clinical nutritionists would ideally help train and play leadership roles in such teams, who would be responsible for assessing patients for their nutritional needs, and ensuring that the feeds provided to patients are appropriate and adequate for their needs.

Predictors of maternal mortality among critically ill obstetric patients

Aim Evaluation of the predictors of maternal mortality among critically ill obstetric patients managed at the intensive care unit (ICU). Methods A case control study to evaluate the predictors of maternal mortality among critically ill obstetric patients managed at the intensive care unit (ICU) of the University of Ilorin Teaching Hospital, Ilorin, Nigeria from 1st January 2010 to 30th June 2013. Participants were critically ill obstetric patients who were admitted and managed at the ICU during the study period. Subjects were those who died while controls were age and parity matched survivors. Statistical analysis was with SPSS-20 to determine chi square, Cox-regression and odds ratio; p value < 0.05 was significant. Results The mean age of subjects and controls were 28.92 ± 5.09 versus 29.44 ± 5.74 (p = 0.736), the level of education was higher among controls (p = 0.048) while more subjects were of low social class (p = 0.321), did not have antenatal care (p = 0.131) and had partners with lower level of education (p = 0.156) compared to controls. The two leading indications for admission among subjects and controls were massive postpartum haemorrhage and severe preeclampsia or eclampsia. The mean duration of admission was higher among controls (3.32 ± 2.46 versus 3.00 ± 2.58; p = 0.656) while the mean cost of ICU care was higher among the subjects (p = 0.472). The statistical significant predictors of maternal deaths were the patient’s level of education, Glasgow Coma Scale (GCS) score, oxygen saturation, multiple organ failure at ICU admission and the need for mechanical ventilation or inotrophic drugs after admission. Conclusion The clinical state at ICU admission of the critically ill obstetric patients is the major outcome determinant. Therefore, early recognition of the need for ICU care, adequate pre-ICU admission supportive care and prompt transfer will improve the outcome.

Critical energy deficit and mortality in critically ill patients

Objective: We investigate the influence of caloric and protein deficit on mortality and length of hospital stay of critically ill patients. Methods: A cohort prospective study including 100 consecutive patients in a tertiary intensive care unit (ICU) receiving enteral or parenteral nutrition. The daily caloric and protein deficit were collected each day for a maximum of 30 days. Energy deficits were divided into critical caloric deficit (≥ 480 kcal/day) and non-critical caloric deficit (≤ 480 kcal/day); and in critical protein deficit (≥ 20 g/day) and non-critical protein deficit (≤ 20 g/day). The findings were correlated with hospital stay and mortality. Results: The mortality rate was 33%. Overall, the patients received 65.4% and 67.7% of the caloric and protein needs. Critical caloric deficit was found in 72% of cases and critical protein deficit in 70% of them. There was a significant correlation between length of stay and accumulated caloric deficit (R = 0.37; p < 0.001) and protein deficit (R = 0.28; p < 0.001). The survival analysis showed that mortality was greater in patients with both critical caloric (p < 0.001) and critical protein deficits (p < 0.01). The Cox regression analysis showed that critical protein deficit was associated with higher mortality (HR 0.25, 95% CI 0.07-0.93, p = 0.03). Conclusions: The incidence of caloric and protein deficit in the ICU is high. Both caloric and protein deficits increase the length of hospital stay, and protein deficit greater than 20 g/day is an independent factor for mortality in critical care unit.

Timing versus caloric goal in nutritional therapy for critically ill patients

Introduction: Enteral nutrition is an important therapy for severely critically ill patients. The timing and amount of energy have been highly debated. Objective: The aim of the present study was to directly compare the timing and the caloric targets in critically ill patients. Methods: Retrospective cohort study conducted at a single center, comparing timing and caloric goal for critically ill patients. Patients were stratified according to the start of nutritional therapy (24, 48, or more than 48 h) and the amount of energy delivered (target adequacy of previously calculated percentage in the first week). Statistical analysis was performed using parametric and non-parametric tests for independent samples and logistic regression. The results were expressed as mean ± standard deviation or incidence and percentage. Results and discussion: There were no differences in major clinical outcomes in relation to the achievement of percentage of caloric goal at the end of the first week of the study. The beginning of caloric intake on the first day of hospitalization was associated with reduced mortality in the intensive care unit, but not with hospital mortality. The strategy of an early and limited amount of calories seems to be associated with a better outcome. Prospective studies evaluating and comparing these strategies are recommended.

Update in the management of critically ill burned patients

The management of critically ill burn patients is challenging. These patients have to be managed in specialized centers, where the expertise of physicians and nursing personnel guarantees the best treatment. Mortality of burn patients has improved over the past decades due to a better understanding of burn shock pathophysiology, optimal surgical management, infection control and nutritional support. Indeed, a more aggressive resuscitation, early excision and grafting, the judicious use of topical antibiotics, and the provision of an adequate calorie and protein intake are key to attain best survival results. General advances in critical care have also to be implemented, including protective ventilation, glycemic control, selective decontamination of the digestive tract, and implementation of sedation protocols.

Bioelectrical impedance analysis predicts outcome in patients with suspected bacteremia

Fluid shifts from intracellular to extracellular water (ICW to ECW) are a feature of sepsis, caused by increased vascular permeability and cell catabolism. Changes in ECW and total body water (TBW) were assessed in a prospective observational study of patients with bacteremia by a bedside technique, and its prognostic impact determined; In 78 hospital patients with fever, the resistance ratio (Rinf/RO) and estimated ECW/TBW ratio from multifrequency bioelectrical impedance analysis, and serum albumin concentration were measured. Rinf/RO and ECW/TBW ratios decreased from day 0 to 2 in patients with significant bacteremia (n = 31), but not in patients with doubtful or negative blood cultures (n = 22 and 25), Increased Rinf/RO at baseline, and further increase of ECW/TBW from day 0 to 2, were associated with lower rate of recovery after 1 week and with higher mortality. Baseline Rinf/RO above the median (0.75) had positive and negative predictive values of 0.31 and 0.95 for death. This prognostic effect was independent of underlying disease and blood culture result in a multivariate model. Hypoalbuminemia at baseline was predictive of outcome, but changes in albumin from day 0 to 2 were unrelated to blood culture results or outcome. In patients with bacteremia,fluid shifts from intracellular to extracellular,vater occur early are rapidly reversible by antibiotic treatment but are associated with adverse prognosis. Bioelectrical impedance deserves further study as a tool for bedside monitoring of patients with bacteremia.

A comparison of observed versus estimated baseline creatinine for determination of RIFLE class in patients with acute kidney injury

Methods. Data from the Beginning and Ending Supportive Therapy for the Kidney (BEST Kidney) study, a prospective observational study from 54 ICUs in 23 countries of critically ill patients with severe AKI, were analysed. The RIFLE class was determined by using observed (o) pre-morbid and estimated (e) baseline SCr values. Agreement was evaluated by correlation coefficients and Bland-Altman plots. Sensitivity analysis by chronic kidney disease (CKD) status was performed. Results. Seventy-six percent of patients (n = 1327) had a pre-morbid baseline SCr, and 1314 had complete data for evaluation. Forty-six percent had CKD. The median (IQR) values were 97 mu mol/L (79-150) for oSCr and 88 mu mol/L (71-97) for eSCr. The oSCr and eSCr determined at ICU admission and at study enrolment showed only a modest correlation (r = 0.49, r = 0.39). At ICU admission and study enrolment, eSCr misclassified 18.8% and 11.7% of patients as having AKI compared with oSCr. Exclusion of CKD patients improved the correlation between oSCr and eSCr at ICU admission and study enrolment (r = 0.90, r = 0.84) resulting in 6.6% and 4.0% being misclassified, respectively. Conclusions. While limited, estimating baseline SCr by the MDRD equation when pre-morbid SCr is unavailable would appear to perform reasonably well for determining the RIFLE categories only if and when pre-morbid GFR was near normal. However, in patients with suspected CKD, the use of MDRD to estimate baseline SCr overestimates the incidence of AKI and should not likely be used. Improved methods to estimate baseline SCr are needed.

Age, invasive ventilatory support and outcomes in elderly patients admitted to intensive care units

Objective: to determine the relationship between age and in-hospital mortality of elderly patients, admitted to ICU, requiring and not requiring invasive ventilatory support. Design: prospective observational cohort study conducted over a period of 11 months. Setting: medical-surgical ICU at a Brazilian university hospital. Subjects: a total of 840 patients aged 55 years and older were admitted to ICU. Methods: in-hospital death rates for patients requiring and not requiring invasive ventilatory support were compared across three successive age intervals (55-64; 65-74 and 75 or more years), adjusting for severity of illness using the Acute Physiologic Score. Results: age was strongly correlated with mortality among the invasively ventilated subgroup of patients and the multivariate adjusted odds ratios increased progressively with every age increment (OR = 1.60, 95% CI = 1.01-2.54 for 65-74 years old and OR = 2.68, 95% CI = 1.58-4.56 for >= 75 years). For the patients not submitted to invasive ventilatory support, age was not independently associated with in-hospital mortality (OR = 2.28, 95% CI = 0.99-5.25 for 65-74 years old and OR = 1.95, 95% CI = 0.82-4.62 for >= 75 years old). Conclusions: the combination of age and invasive mechanical ventilation is strongly associated with in-hospital mortality. Age should not be considered as a factor related to in-hospital mortality of elderly patients not requiring invasive ventilatory support in ICU.

Thalidomide treatment down-regulates SDF-1 alpha and CXCR4 expression in multiple myeloma patients

The chemokine stromal-derived factor-1 alpha (SDF-1 alpha) and its receptor CXCR4 are critically involved in directional migration and homing of plasma cells in multiple myeloma. Here, we show that the expression of SDF-1 alpha and CXCR4 was significantly down-regulated in patients treated with thalidomide (n = 10) as compared to newly diagnosed MM patients (n = 31) and MM patients treated with other drugs (n = 38). SDF-1 alpha and CXCR4 expression was also significantly decreased in a RPMI 8226 cell line treated with 10 and 20 mu mol/L of thalidomide. Our findings indicate that thalidomide therapy induces down-regulation of CXCR4 and its ligand SDF-1 alpha in multiple myeloma. (c) 2008 Elsevier Ltd. All rights reserved.