Introducing an integrated intermediate care unit improves ICU utilization: a prospective intervention study.

BACKGROUND: Improvement of appropriate bed use and access to intensive care (ICU) beds is essential in optimizing utilization of ICU capacity. The introduction of an intermediate care unit (IMC) integrated in the ICU care may improve this utilization. METHOD: In a before-after prospective intervention study in a university hospital mixed ICU, the impact of introducing a six-bed mixed IMC unit supervised and staffed by ICU physicians was investigated. Changes in ICU utilization (length of stay, frequency of mechanical ventilation use), nursing workload assessed byTISS-28 score, as well as inappropriate bed use, accessibility of the ICU (number of referrals), and clinical outcome indicators (readmission and mortality rates) were measured. RESULTS: During 17 months, data of 1027 ICU patients were collected. ICU utilization improved significantly with an increased appropriate use of ICU beds. However, the number of referrals, readmissions to the ICU and mortality rates did not decrease after the IMC was opened. CONCLUSION: The IMC contributed to a more appropriate use of ICU facilities and did result in a significant increase in mean nursing workload at the ICU.

The Surviving Sepsis Campaign: results of an international guideline-based performance improvement program targeting severe sepsis.

OBJECTIVE: The Surviving Sepsis Campaign (SSC or "the Campaign") developed guidelines for management of severe sepsis and septic shock. A performance improvement initiative targeted changing clinical behavior (process improvement) via bundles based on key SSC guideline recommendations. DESIGN AND SETTING: A multifaceted intervention to facilitate compliance with selected guideline recommendations in the intensive care unit, emergency department, and wards of individual hospitals and regional hospital networks was implemented voluntarily in the United States, Europe, and South America. Elements of the guidelines were "bundled" into two sets of targets to be completed within 6 hrs and within 24 hrs. An analysis was conducted on data submitted from January 2005 through March 2008. SUBJECTS: A total of 15,022 subjects. MEASUREMENTS AND MAIN RESULTS: Data from 15,022 subjects at 165 sites were analyzed to determine the compliance with bundle targets and association with hospital mortality. Compliance with the entire resuscitation bundle increased linearly from 10.9% in the first site quarter to 31.3% by the end of 2 yrs (p < .0001). Compliance with the entire management bundle started at 18.4% in the first quarter and increased to 36.1% by the end of 2 yrs (p = .008). Compliance with all bundle elements increased significantly, except for inspiratory plateau pressure, which was high at baseline. Unadjusted hospital mortality decreased from 37% to 30.8% over 2 yrs (p = .001). The adjusted odds ratio for mortality improved the longer a site was in the Campaign, resulting in an adjusted absolute drop of 0.8% per quarter and 5.4% over 2 yrs (95% confidence interval, 2.5-8.4). CONCLUSIONS: The Campaign was associated with sustained, continuous quality improvement in sepsis care. Although not necessarily cause and effect, a reduction in reported hospital mortality rates was associated with participation. The implications of this study may serve as an impetus for similar improvement efforts.

Global utilization of low-dose corticosteroids in severe sepsis and septic shock: a report from the PROGRESS registry.

INTRODUCTION: The benefits and use of low-dose corticosteroids (LDCs) in severe sepsis and septic shock remain controversial. Surviving sepsis campaign guidelines suggest LDC use for septic shock patients poorly responsive to fluid resuscitation and vasopressor therapy. Their use is suspected to be wide-spread, but paucity of data regarding global practice exists. The purpose of this study was to compare baseline characteristics and clinical outcomes of patients treated or not treated with LDC from the international PROGRESS (PROmoting Global Research Excellence in Severe Sepsis) cohort study of severe sepsis. METHODS: Patients enrolled in the PROGRESS registry were evaluated for use of vasopressor and LDC (equivalent or lesser potency to hydrocortisone 50 mg six-hourly plus 50 microg 9-alpha-fludrocortisone) for treatment of severe sepsis at any time in intensive care units (ICUs). Baseline characteristics and hospital mortality were analyzed, and logistic regression techniques used to develop propensity score and outcome models adjusted for baseline imbalances between groups. RESULTS: A total of 8,968 patients with severe sepsis and sufficient data for analysis were studied. A total of 79.8% (7,160/8,968) of patients received vasopressors, and 34.0% (3,051/8,968) of patients received LDC. Regional use of LDC was highest in Europe (51.1%) and lowest in Asia (21.6%). Country use was highest in Brazil (62.9%) and lowest in Malaysia (9.0%). A total of 14.2% of patients on LDC were not receiving any vasopressor therapy. LDC patients were older, had more co-morbidities and higher disease severity scores. Patients receiving LDC spent longer in ICU than patients who did not (median of 12 versus 8 days; P <0.001). Overall hospital mortality rates were greater in the LDC than in the non-LDC group (58.0% versus 43.0%; P <0.001). After adjusting for baseline imbalances, in all mortality models (with vasopressor use), a consistent association remained between LDC and hospital mortality (odds ratios varying from 1.30 to 1.47). CONCLUSIONS: Widespread use of LDC for the treatment of severe sepsis with significant regional and country variation exists. In this study, 14.2% of patients received LDC despite the absence of evidence of shock. Hospital mortality was higher in the LDC group and remained higher after adjustment for key determinates of mortality.

Predisposition, insult/infection, response, and organ dysfunction: A new model for staging severe sepsis.

OBJECTIVE: To generate and validate an initial version of the predisposition, insult/infection, response, and organ dysfunction (PIRO) staging model for risk stratification in severe sepsis. The goal was to create distinct levels of mortality risk within each of the four categories (P, I, R, and O), and that these risk levels would be meaningful in terms of prediction independent of the other categories. DESIGN: : Retrospective analysis using a statistical model utilizing two large, global databases of patients with severe sepsis. SETTING AND PATIENTS: Database #1: Placebo-treated patients from a phase III clinical trial of patients with severe sepsis (PROtein C Worldwide Evaluation in Severe Sepsis [PROWESS], 840 patients). Database #2: Global severe sepsis registry performed in 276 intensive care units in 37 countries (PROmoting Global Research Excellence in Severe Sepsis [PROGRESS], 10,610 patients). INTERVENTIONS: None. METHODS: Classification and regression trees were used to classify patients and derive a scoring system from the PROWESS and PROGRESS databases with internal validation. Regression tree parameters included Chi-square tests and a minimum of five patients per node. The risk levels were done in a stepwise manner, adjusting for the previous categories. Initially, the predisposition scoring was developed, and subsequently, the infection scoring was then developed after adjusting for the predisposition levels, and so on. Logistic regression analyses, odds ratios, and area under the receiver operator characteristic curve were used to evaluate the scoring systems. MEASUREMENTS AND MAIN RESULTS: Each of the four PIRO components had similar odds ratios in multivariable logistic regressions. In PROWESS, the correlation of the PIRO total score and in-hospital mortality rates was 0.974 (p < 0.0001), and in PROGRESS, the correlation of the PIRO total score and hospital mortality rates was 0.998 (p < 0.0001). CONCLUSIONS: PIRO can develop into an effective model for staging severe sepsis, seems to be predictive of mortality, and may be useful in future sepsis research.

An international survey: Public awareness and perception of sepsis.

BACKGROUND: Sepsis is a common cause of death throughout the world. Early treatment improves outcome; however, treatment may be delayed if the patient does not present himself/herself for medical care until late in the disease process. Lack of knowledge about the syndrome may contribute to delay in presenting for medical care. However, we need to acknowledge the complexity of sepsis. General awareness of sepsis by the public may increase political pressure for research funding. Increased public awareness of acute myocardial infarction has contributed to reduced mortality over the last 50 yrs. This example provides a rationale for future efforts to increase the public awareness of sepsis. OBJECTIVE: The survey was designed to gain insight into public perceptions and attitudes regarding sepsis. DESIGN: Prospective, international survey performed using structured telephone interviews. SUBJECTS: A total of 6021 interviewees, 5021 in Europe and 1000 in the United States. MEASUREMENTS AND MAIN RESULTS: In Italy, Spain, the United Kingdom, France and the United States, a mean of 88% of interviewees had never heard of the term "sepsis". In Germany 53% of people knew the word sepsis. In Italy, Spain, United Kingdom, France, and United States, of people who recognized the term sepsis, 58% did not recognize that sepsis is a leading cause of death. CONCLUSIONS: There is poor public awareness about the existence of a syndrome known as sepsis. Results of this questionnaire underscore the challenges in early management and treatment of infected patients at risk for developing sepsis syndrome.

Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock: 2008.

OBJECTIVE: To provide an update to the original Surviving Sepsis Campaign clinical management guidelines, "Surviving Sepsis Campaign Guidelines for Management of Severe Sepsis and Septic Shock," published in 2004. DESIGN: Modified Delphi method with a consensus conference of 55 international experts, several subsequent meetings of subgroups and key individuals, teleconferences, and electronic-based discussion among subgroups and among the entire committee. This process was conducted independently of any industry funding. METHODS: We used the Grades of Recommendation, Assessment, Development and Evaluation (GRADE) system to guide assessment of quality of evidence from high (A) to very low (D) and to determine the strength of recommendations. A strong recommendation (1) indicates that an intervention's desirable effects clearly outweigh its undesirable effects (risk, burden, cost) or clearly do not. Weak recommendations (2) indicate that the tradeoff between desirable and undesirable effects is less clear. The grade of strong or weak is considered of greater clinical importance than a difference in letter level of quality of evidence. In areas without complete agreement, a formal process of resolution was developed and applied. Recommendations are grouped into those directly targeting severe sepsis, recommendations targeting general care of the critically ill patient that are considered high priority in severe sepsis, and pediatric considerations. RESULTS: Key recommendations, listed by category, include early goal-directed resuscitation of the septic patient during the first 6 hrs after recognition (1C); blood cultures before antibiotic therapy (1C); imaging studies performed promptly to confirm potential source of infection (1C); administration of broad-spectrum antibiotic therapy within 1 hr of diagnosis of septic shock (1B) and severe sepsis without septic shock (1D); reassessment of antibiotic therapy with microbiology and clinical data to narrow coverage, when appropriate (1C); a usual 7-10 days of antibiotic therapy guided by clinical response (1D); source control with attention to the balance of risks and benefits of the chosen method (1C); administration of either crystalloid or colloid fluid resuscitation (1B); fluid challenge to restore mean circulating filling pressure (1C); reduction in rate of fluid administration with rising filing pressures and no improvement in tissue perfusion (1D); vasopressor preference for norepinephrine or dopamine to maintain an initial target of mean arterial pressure > or = 65 mm Hg (1C); dobutamine inotropic therapy when cardiac output remains low despite fluid resuscitation and combined inotropic/vasopressor therapy (1C); stress-dose steroid therapy given only in septic shock after blood pressure is identified to be poorly responsive to fluid and vasopressor therapy (2C); recombinant activated protein C in patients with severe sepsis and clinical assessment of high risk for death (2B except 2C for postoperative patients). In the absence of tissue hypoperfusion, coronary artery disease, or acute hemorrhage, target a hemoglobin of 7-9 g/dL (1B); a low tidal volume (1B) and limitation of inspiratory plateau pressure strategy (1C) for acute lung injury (ALI)/acute respiratory distress syndrome (ARDS); application of at least a minimal amount of positive end-expiratory pressure in acute lung injury (1C); head of bed elevation in mechanically ventilated patients unless contraindicated (1B); avoiding routine use of pulmonary artery catheters in ALI/ARDS (1A); to decrease days of mechanical ventilation and ICU length of stay, a conservative fluid strategy for patients with established ALI/ARDS who are not in shock (1C); protocols for weaning and sedation/analgesia (1B); using either intermittent bolus sedation or continuous infusion sedation with daily interruptions or lightening (1B); avoidance of neuromuscular blockers, if at all possible (1B); institution of glycemic control (1B), targeting a blood glucose < 150 mg/dL after initial stabilization (2C); equivalency of continuous veno-veno hemofiltration or intermittent hemodialysis (2B); prophylaxis for deep vein thrombosis (1A); use of stress ulcer prophylaxis to prevent upper gastrointestinal bleeding using H2 blockers (1A) or proton pump inhibitors (1B); and consideration of limitation of support where appropriate (1D). Recommendations specific to pediatric severe sepsis include greater use of physical examination therapeutic end points (2C); dopamine as the first drug of choice for hypotension (2C); steroids only in children with suspected or proven adrenal insufficiency (2C); and a recommendation against the use of recombinant activated protein C in children (1B). CONCLUSIONS: There was strong agreement among a large cohort of international experts regarding many level 1 recommendations for the best current care of patients with severe sepsis. Evidenced-based recommendations regarding the acute management of sepsis and septic shock are the first step toward improved outcomes for this important group of critically ill patients.

Influence of antibiotic therapy on the cytological diagnosis of ventilator-associated pneumonia.

OBJECTIVE: To assess the influence of antibiotics on the value of various cytological parameters, and their combinations, in diagnosing ventilator-associated pneumonia (VAP). DESIGN: Prospective study. SETTING: The general intensive care unit (17 beds) of the University Hospital Maastricht. PATIENTS: Three hundred and thirty-five episodes of clinically suspected VAP (defined by the clinical and radiological criteria previously described by Bonten et al.) in 282 patients were studied. INTERVENTIONS: No additional interventions were conducted. MEASUREMENTS AND RESULTS: Bronchoalveolar lavage fluid cytology included a total cell count per millilitre, differential cell count and the percentage of infected cells (cells containing phagocytised organisms). Antibiotic therapy from 72 h prior to lavage was recorded. Areas under the curve (AUCs) of receiver operating characteristic curves were calculated for various cytological parameters and their combinations, in patients with and without antibiotic therapy. In 126 episodes (37.6%) in 106 patients, VAP was confirmed. There was no difference in AUCs between patients with and without antibiotic therapy for any parameter studied. The most prominent AUCs were (for patient groups with and without antibiotics combined): total cell count, 0.65; percentage polymorphonuclear neutrophils, 0.71; and percentage infected cells, 0.90. The combination of percentage infected cells with any other cytological parameter did not increase the AUC. CONCLUSION: Antibiotic therapy did not influence the predictive value of the percentage infected cells in BALF in diagnosing VAP.

Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock: 2008.

OBJECTIVE: To provide an update to the original Surviving Sepsis Campaign clinical management guidelines, "Surviving Sepsis Campaign guidelines for management of severe sepsis and septic shock," published in 2004. DESIGN: Modified Delphi method with a consensus conference of 55 international experts, several subsequent meetings of subgroups and key individuals, teleconferences, and electronic-based discussion among subgroups and among the entire committee. This process was conducted independently of any industry funding. METHODS: We used the GRADE system to guide assessment of quality of evidence from high (A) to very low (D) and to determine the strength of recommendations. A strong recommendation indicates that an intervention's desirable effects clearly outweigh its undesirable effects (risk, burden, cost), or clearly do not. Weak recommendations indicate that the tradeoff between desirable and undesirable effects is less clear. The grade of strong or weak is considered of greater clinical importance than a difference in letter level of quality of evidence. In areas without complete agreement, a formal process of resolution was developed and applied. Recommendations are grouped into those directly targeting severe sepsis, recommendations targeting general care of the critically ill patient that are considered high priority in severe sepsis, and pediatric considerations. RESULTS: Key recommendations, listed by category, include: early goal-directed resuscitation of the septic patient during the first 6 hrs after recognition (1C); blood cultures prior to antibiotic therapy (1C); imaging studies performed promptly to confirm potential source of infection (1C); administration of broad-spectrum antibiotic therapy within 1 hr of diagnosis of septic shock (1B) and severe sepsis without septic shock (1D); reassessment of antibiotic therapy with microbiology and clinical data to narrow coverage, when appropriate (1C); a usual 7-10 days of antibiotic therapy guided by clinical response (1D); source control with attention to the balance of risks and benefits of the chosen method (1C); administration of either crystalloid or colloid fluid resuscitation (1B); fluid challenge to restore mean circulating filling pressure (1C); reduction in rate of fluid administration with rising filing pressures and no improvement in tissue perfusion (1D); vasopressor preference for norepinephrine or dopamine to maintain an initial target of mean arterial pressure > or = 65 mm Hg (1C); dobutamine inotropic therapy when cardiac output remains low despite fluid resuscitation and combined inotropic/vasopressor therapy (1C); stress-dose steroid therapy given only in septic shock after blood pressure is identified to be poorly responsive to fluid and vasopressor therapy (2C); recombinant activated protein C in patients with severe sepsis and clinical assessment of high risk for death (2B except 2C for post-operative patients). In the absence of tissue hypoperfusion, coronary artery disease, or acute hemorrhage, target a hemoglobin of 7-9 g/dL (1B); a low tidal volume (1B) and limitation of inspiratory plateau pressure strategy (1C) for acute lung injury (ALI)/acute respiratory distress syndrome (ARDS); application of at least a minimal amount of positive end-expiratory pressure in acute lung injury (1C); head of bed elevation in mechanically ventilated patients unless contraindicated (1B); avoiding routine use of pulmonary artery catheters in ALI/ARDS (1A); to decrease days of mechanical ventilation and ICU length of stay, a conservative fluid strategy for patients with established ALI/ARDS who are not in shock (1C); protocols for weaning and sedation/analgesia (1B); using either intermittent bolus sedation or continuous infusion sedation with daily interruptions or lightening (1B); avoidance of neuromuscular blockers, if at all possible (1B); institution of glycemic control (1B) targeting a blood glucose < 150 mg/dL after initial stabilization ( 2C ); equivalency of continuous veno-veno hemofiltration or intermittent hemodialysis (2B); prophylaxis for deep vein thrombosis (1A); use of stress ulcer prophylaxis to prevent upper GI bleeding using H2 blockers (1A) or proton pump inhibitors (1B); and consideration of limitation of support where appropriate (1D). Recommendations specific to pediatric severe sepsis include: greater use of physical examination therapeutic end points (2C); dopamine as the first drug of choice for hypotension (2C); steroids only in children with suspected or proven adrenal insufficiency (2C); a recommendation against the use of recombinant activated protein C in children (1B). CONCLUSION: There was strong agreement among a large cohort of international experts regarding many level 1 recommendations for the best current care of patients with severe sepsis. Evidenced-based recommendations regarding the acute management of sepsis and septic shock are the first step toward improved outcomes for this important group of critically ill patients.

Changes in hospital costs after introducing an intermediate care unit: a comparative observational study.

INTRODUCTION: The high cost of critical care resources has resulted in strategies to reduce the costs of ruling out low-risk patients by developing intermediate care units (IMCs). The aim of this study was to compare changes in total hospital costs for intensive care patients before and after the introduction of an IMC at the University Hospital Maastricht. METHODS: The design was a comparative longitudinal study. The setting was a university hospital with a mixed intensive care unit (ICU), an IMC, and general wards. Changes in total hospital costs were measured for patients who were admitted to the ICU before and after the introduction of the IMC. The comparison of interest was the opening of a six-bed mixed IMC. RESULTS: The mean total hospital cost per patient increased significantly. Before the introduction of the IMC, the total hospital cost per patient was n12,961 (+/- n14,530) and afterwards it rose to n16,513 (+/- n17,718). Multiple regression analysis was used to determine to what extent patient characteristics explained these higher hospital costs using mortality, type of stay, diagnostic categories, length of ICU and ward stay, and the Therapeutic Intervention Scoring System (TISS) as predictors. More surgical patients, greater requirements of therapeutic interventions on the ICU admission day, and longer ICU stay in patients did explain the increase in hospital costs, rather than the introduction of the IMC. CONCLUSION: After the introduction of the IMC, the higher mean total hospital costs for patients with a high TISS score and longer ICU stay explained the cost increase.

International integrated database for the evaluation of severe sepsis and drotrecogin alfa (activated) therapy: analysis of efficacy and safety data in a large surgical cohort.

BACKGROUND: The International Integrated Database for the Evaluation of Severe Sepsis and Drotrecogin alfa (activated) Therapy includes an extensive cohort of surgical patients (1659/4459; 37%). This database broadens the experience reported on a comparatively small set of surgical patients from the pivotal Protein C Worldwide Evaluation in Severe Sepsis trial to examine issues of safety and efficacy in a much larger cohort. METHODS: We conducted a retrospective analysis of prospectively defined outcomes from 5 integrated clinical studies of severe sepsis. Multivariable analyses incorporated propensity scores, treatment, and significant baseline risk factors as independent variables in logistic regression models for 2 outcomes: serious adverse events that were observed during infusion and 28-day, all-cause mortality rates. Adjusted odds ratios were calculated for clinically important strata. Multiple subcategories of serious bleeding-event rates are presented. RESULTS: Although surgical patients who were treated with drotrecogin alfa [activated] (DrotAA) experienced a greater proportion of serious bleeding events during the infusion period, most of the patients were treated without fatal consequence. A 10.7% absolute all cause mortality risk reduction (adjusted odds ratio, 0.66; 95% CI, 0.45-0.97) was observed for DrotAA-treated, high-risk (Acute Physiology and Chronic Health Evaluation II, >/= 25) surgical patients. We could not demonstrate a survival benefit in DrotAA-treated, low-risk (Acute Physiology and Chronic Health Evaluation II, <25) surgical patients. When surgical patients were stratified by number of organ dysfunctions, absolute risk reductions were observed in both categories: multiorgan (4.3%) and single (4.5%). CONCLUSION: International Integrated Database for the Evaluation of Severe Sepsis and Drotrecogin alfa (activated) Therapy analyses affirmed the favorable benefit/risk profile of DrotAA for surgical patients. The serious adverse event rate that was experienced by surgical patients during the study drug infusion period was 7.5% in the DrotAA-treated group versus 6.3% in the placebo-treated group (odds ratio, 1.41; 95% CI, 0.89-2.25). The clinical benefit of DrotAA therapy paralleled baseline risk of death and substantiated findings from the Protein C Worldwide Evaluation in Severe Sepsis study. Future analyses are needed to evaluate the special relationships among sepsis severity, bleeding management, and the postoperative timing of DrotAA administration.

International integrated database for the evaluation of severe sepsis and drotrecogin alfa (activated) therapy: analysis of efficacy and safety data in a large surgical cohort.

BACKGROUND: The International Integrated Database for the Evaluation of Severe Sepsis and Drotrecogin alfa (activated) Therapy includes an extensive cohort of surgical patients (1659/4459; 37%). This database broadens the experience reported on a comparatively small set of surgical patients from the pivotal Protein C Worldwide Evaluation in Severe Sepsis trial to examine issues of safety and efficacy in a much larger cohort. METHODS: We conducted a retrospective analysis of prospectively defined outcomes from 5 integrated clinical studies of severe sepsis. Multivariable analyses incorporated propensity scores, treatment, and significant baseline risk factors as independent variables in logistic regression models for 2 outcomes: serious adverse events that were observed during infusion and 28-day, all-cause mortality rates. Adjusted odds ratios were calculated for clinically important strata. Multiple subcategories of serious bleeding-event rates are presented. RESULTS: Although surgical patients who were treated with drotrecogin alfa [activated] (DrotAA) experienced a greater proportion of serious bleeding events during the infusion period, most of the patients were treated without fatal consequence. A 10.7% absolute all cause mortality risk reduction (adjusted odds ratio, 0.66; 95% CI, 0.45-0.97) was observed for DrotAA-treated, high-risk (Acute Physiology and Chronic Health Evaluation II, >or=25) surgical patients. We could not demonstrate a survival benefit in DrotAA-treated, low-risk (Acute Physiology and Chronic Health Evaluation II, <25) surgical patients. When surgical patients were stratified by number of organ dysfunctions, absolute risk reductions were observed in both categories: multiorgan (4.3%) and single (4.5%). CONCLUSION: International Integrated Database for the Evaluation of Severe Sepsis and Drotrecogin alfa (activated) Therapy analyses affirmed the favorable benefit/risk profile of DrotAA for surgical patients. The serious adverse event rate that was experienced by surgical patients during the study drug infusion period was 7.5% in the DrotAA-treated group versus 6.3% in the placebo-treated group (odds ratio, 1.41; 95% CI, 0.89-2.25). The clinical benefit of DrotAA therapy paralleled baseline risk of death and substantiated findings from the Protein C Worldwide Evaluation in Severe Sepsis study. Future analyses are needed to evaluate the special relationships among sepsis severity, bleeding management, and the postoperative timing of DrotAA administration.

Point-of-care blood analyzer during the interhospital transport of critically ill children.

OBJECTIVES: To investigate the influence of point-of-care laboratory results (arterial blood gases, ionized calcium, potassium, sodium, glucose, hematocrit and hemoglobin) on therapeutic interventions during interhospital pediatric intensive care transport. DESIGN: Prospective observational study. SETTINGS: Specialist pediatric intensive care retrieval team of a university hospital. PARTICIPANTS: Critically ill pediatric patients who were referred from a community hospital to a pediatric intensive care of a tertiary center. The retrieval team sampled arterial blood during the time of stabilization in the referring hospital and during transport. All results were recorded and for each result the physician of the specialist retrieval team wrote down the influence on the treatment (none, partly, only). The physician specified the kind of intervention. RESULTS: Point-of-care blood analyses influenced the therapeutic management in 76.5% of all blood samples and in 86.2% of the referred patients. Of all interventions, 42.9% were based only on the laboratory results. The majority of interventions were adjustments of the mechanical ventilation. Point-of-care blood analyses reduced the delay in treatment of potentially life-threatening abnormalities of laboratory results (severe hypokalemia and low hematocrit). CONCLUSIONS: During interhospital pediatric intensive care transport, point-of-care blood analyses frequently led to therapeutic interventions. Some abnormal blood results were potentially life threatening and could not have been discovered without point-of-care measurement. We therefore recommend the use of a point-of-care blood analyzer during interhospital intensive care transports, not only for blood gases but also for electrolytes, glucose and hematocrit.

Meta-analysis of hemodynamic optimization: relationship to methodological quality.

INTRODUCTION: To review systematically the effect of interventions aimed at hemodynamic optimization and to relate this to the quality of individual published trials. METHODS: A systematic, computerized bibliographic search of published studies and citation reviews of relevant studies was performed. All randomized clinical trials in which adult patients were included in a trial deliberately aiming at an optimized or maximized hemodynamic condition of the patients (with oxygen delivery, cardiac index, oxygen consumption, mixed venous oxygen saturation and/or stroke volume as end-points) were selected. A total of 30 studies were selected for independent review. Two reviewers extracted data on population, intervention, outcome and methodological quality. Agreement between reviewers was high: differences were eventually resolved by third-party decision. The methodological quality of the studies was moderate (mean 9.0, SD 1.7), and the outcomes of the randomized clinical trials were not related to their quality. RESULTS: Efforts to achieve an optimized hemodynamic condition resulted in a decreased mortality rate (relative risk ratio (RR) 0.75 (95% confidence interval (CI) 0.62 to 0.90) in all studies combined. This was due to a significantly decreased mortality in peri-operative intervention studies (RR 0.66 (95% CI 0.54 to 0.81). Overall, patients with sepsis and overt organ failure do not benefit from this method (RR 0.92 (95% CI 0.75 to 1.11)). CONCLUSION: This systematic review showed that interventions aimed at hemodynamic optimization reduced mortality. In particular, trials including peri-operative interventions aimed at the hemodynamic optimization of high-risk surgical patients reduce mortality. Overall, this effect was not related to the trial quality.

The role of arginine in infection and sepsis.

Sepsis is a systemic response to an infection, with high morbidity and mortality rates. Metabolic changes during infection and sepsis could be related to changes in metabolism of the amino acid L-arginine. In sepsis, protein breakdown is increased, which is a key process to maintain arginine delivery because both endogenous de novo arginine production from citrulline and food intake are reduced. Arginine catabolism, on the other hand, is markedly increased by enhanced use of arginine via the arginase and nitric oxide pathways. As a result, lowered plasma arginine levels are usually found. Arginine may therefore be considered as an essential amino acid in sepsis, and supplementation could be beneficial in sepsis by improving microcirculation and protein anabolism. L-Arginine supplementation in a hyperdynamic pig model of sepsis prohibits the increase in pulmonary arterial blood pressure, improves muscle and liver protein metabolism, and restores the intestinal motility pattern. Arguments raised against arginine supplementation are mainly pointed at stimulating nitric oxide (NO) production, with concerns about toxicity of increased NO and hemodynamic instability with refractory hypotension. NO synthase inhibition, however, increased mortality. Arginine supplementation in septic patients has transient effects on hemodynamics when supplied as a bolus but seems without hemodynamic side effects when supplied continuously. In conclusion, arginine could have an essential role in infection and sepsis.

Measurement of nursing care time of specific interventions on a hematology-oncology unit related to diagnostic categories.

The aim of this study was to develop a tool that can aid nurse managers in planning nurse staffing levels and assessing workload in hematology-oncology wards. A task-oriented method based on a time-and-motion study was used. Three general nursing procedures and 7 specific oncologic and hematologic activities were clocked. It was checked in the charts of the patient, for each day of the admission, how often selected nursing procedures were performed. Then total amount of time needed for each patient was calculated. Data from 29 admissions to the ward were analyzed and divided into 5 categories based upon the treatment performed during that admission. The categories chosen were: autologous stem cell transplantation, allogeneic stem cell transplantation, graft versus host reaction, leukemia treatment, and chemotherapy for solid neoplasm. The results obtained are an estimate of the different daily workload that is required for these categories of patients in selected nursing procedures.

All great truths are iconoclastic: selective decontamination of the digestive tract moves from heresy to level 1 truth.

OBJECTIVE: The objective was to compare evidence of the effectiveness, costs and safety of the traditional parenteral antibiotic-only approach against that gathered from 53 randomised trials involving more than 8,500 patients and six meta-analyses on selective decontamination of the digestive tract (SDD) to control infection on the intensive care unit (ICU). PHILOSOPHY: Traditionalists believe that all infections are due to breaches of hygiene except those established in the first 2 days, and that all micro-organisms can cause death. In contrast, newer insights show that transmission via the hands of carers are responsible only for infections occurring after one week, and that only a limited range of 15 potential pathogens contribute to mortality. INTERVENTIONS TO PREVENT ICU INFECTION: The traditional approach is based on hand disinfection aiming at the prevention of transmission of all micro-organisms, to control all infections that occur after 2 days on the ICU. The second feature is the restrictive use of systemic antibiotics, only in cases of microbiologically proven infection. In contrast, SDD aims to control the three types of infection: primary, secondary endogenous and exogenous due to 15 potential pathogens. The classical SDD tetralogy comprises four components: (i) a parenteral antibiotic, cefotaxime, administered for three days to prevent primary endogenous infections typically occurring "early"; (ii) the oropharyngeal and enteral antimicrobials, polymyxin E, tobramycin and amphotericin B administered in throat and gut throughout the treatment on the ICU to prevent secondary endogenous infections tending to develop "late"; (iii) a high standard of hygiene to control transmission of potential pathogens; and (iv) surveillance samples of throat and rectum to monitor the efficacy of the treatment. ENDPOINTS: (i) Infectious morbidity; (ii) mortality; (iii) antimicrobial resistance; and (iv) costs. RESULTS: Properly designed trials on hand disinfection have never demonstrated a reduction in either pneumonia and septicaemia, or mortality. Two randomised trials using restrictive antibiotic policies failed to show a survival benefit at 28 days. In both trials the proportion of resistant isolates obtained from the lower ways was >60% despite significantly less use of antibiotics in the test group. A formal cost effectiveness analysis of the traditional antibiotic policies has not been performed. On the other hand, two meta-analyses have shown that SDD reduces the odds ratio for lower airway infections to 0.35 (0.29-0.41) and mortality to 0.80 (0.69-0.93), with a 6% overall mortality reduction from 30% to 24%. No increase in the rate of super infections due to resistant bacteria could be demonstrated over a period of 20 years of clinical research. Four randomised trials found the cost per survivor to be substantially lower in patients receiving SDD than for those traditionally managed. CONCLUSIONS: The traditionalists still rely on level 5 evidence, i.e. expert opinion, with a grade E recommendation, whilst the proponents of SDD are able to cite level 1 evidence allowing a grade A recommendation in their attempts to control infection on the ICU. The main reason for SDD not being widely used is the primacy of opinion over evidence.

Gastric PgCO2 and Pg-aCO2 gap are related to D-lactate and not to L-lactate levels in patients with septic shock.

OBJECTIVE: Intestinal ischemia causes an increase in lactate production and gastric intramucosal carbon dioxide partial pressure (PgCO(2)). However, no linear relationship between systemic l-lactate levels and gastric tonometry during intestinal ischemia has been found, probably since l-lactate is rapidly cleared from the circulation by the liver. In contrast, the rate of d-lactate clearance from the circulation by the liver is considerably lower than that of l-lactate, and d-lactate may therefore be more closely related to measurements of gastric tonometry than l-lactate values. DESIGN AND SETTING: Prospective, observational study in a university-affiliated mixed intensive care unit. SUBJECTS: Twenty critically ill patients with septic shock. MEASUREMENTS AND RESULTS: During the first 24 h of admission to the intensive care unit at least two blood samples were taken for d- and l-lactate measurements and arterial blood gases, Simultaneously, gastric PgCO(2) was measured using capnographic tonometry. The intramucosal-arterial PCO(2) gap was calculated using gastric intramucosal PgCO(2) and arterial PCO(2) from arterial blood. d-Lactate was significantly correlated to PgCO(2) values and to the mucosal-arterial PCO(2) gap. There was no relationship between l-lactate and PgCO(2) or the mucosal-arterial PCO(2) gap. d-lactate and l-lactate values were significantly correlated. CONCLUSIONS: During sepsis intestinal production of d-lactate is related to gastric intramucosal PCO(2). No such relationship was found between l-lactate values and PgCO(2)

2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference.

OBJECTIVE: In 1991, the American College of Chest Physicians (ACCP) and the Society of Critical Care Medicine (SCCM) convened a "Consensus Conference," the goals of which were to "provide a conceptual and a practical framework to define the systemic inflammatory response to infection, which is a progressive injurious process that falls under the generalized term 'sepsis' and includes sepsis-associated organ dysfunction as well. The general definitions introduced as a result of that conference have been widely used in practice, and have served as the foundation for inclusion criteria for numerous clinical trials of therapeutic interventions. Nevertheless, there has been an impetus from experts in the field to modify these definitions to reflect our current understanding of the pathophysiology of these syndromes. DESIGN: Several North American and European intensive care societies agreed to revisit the definitions for sepsis and related conditions. This conference was sponsored by the Society of Critical Care Medicine (SCCM), The European Society of Intensive Care Medicine (ESICM), The American College of Chest Physicians (ACCP), the American Thoracic Society (ATS), and the Surgical Infection Society (SIS). METHODS: 29 participants attended the conference from Europe and North America. In advance of the conference, subgroups were formed to evaluate the following areas: signs and symptoms of sepsis, cell markers, cytokines, microbiologic data, and coagulation parameters. The present manuscript serves as the final report of the 2001 International Sepsis Definitions Conference. CONCLUSION: 1. Current concepts of sepsis, severe sepsis and septic shock remain useful to clinicians and researchers. 2. These definitions do not allow precise staging or prognostication of the host response to infection. 3. While SIRS remains a useful concept, the diagnostic criteria for SIRS published in 1992 are overly sensitive and non-specific. 4. An expanded list of signs and symptoms of sepsis may better reflect the clinical response to infection. 6. PIRO, a hypothetical model for staging sepsis is presented, which, in the future, may better characterize the syndrome on the basis of predisposing factors and premorbid conditions, the nature of the underlying infection, the characteristics of the host response, and the extent of the resultant organ dysfunction.

High levels of sulfated mucins in bronchoalveolar lavage fluid of ICU patients with ventilator-associated pneumonia.

OBJECTIVE: To compare the levels of sulfated mucins in bronchoalveolar lavage fluid (BALF) in ICU patients with ventilator-associated pneumonia (VAP) with those in non-infectious controls, i.e., ventilated ICU patients without VAP, and nonventilated patients. DESIGN AND SETTING: Prospective study in a mixed intensive care unit and outpatient clinic of a university hospital. PATIENTS: The study included 56 ventilated ICU patients with VAP, 21 ventilated ICU patients without VAP, and 26 nonventilated outpatients with no pulmonary infection. MEASUREMENTS AND RESULTS: Total cell count and differential cell count of BALF samples were determined, and sulfated mucin levels were measured. For this we used the monoclonal antibody F2 against the sulfated Lewis C structure (SO(3)-3Galbeta1-3GlcNAc). Sulfated mucin levels were significantly increased in ICU patients with VAP than in those without VAP and nonventilated patients. No statistical difference was found between the two groups of ICU patients regarding APACHE II score and the duration of mechanical ventilation prior to the bronchoalveolar lavage. CONCLUSIONS: The increased levels of sulfated mucins in ICU patients with VAP are associated with infection and not with ventilation. The increase in sulfated mucins may favor the persistence of those micro-organisms that possess mucin sulfatase activity, which enable them to survive within the mucus, especially Pseudomonas aeruginosa.