[Critical care of Onco-hematology patients: new therapeutic targets, new complications and new admission policies]. / Réanimation des patients d'onco-hématologie: nouvelles thérapeutiques, nouvelles complications, nouveaux contrats d'admission.

Overall prognosis of cancer or haematological has dramatically decreased over the last decades. Thus advances regarding cancer or haematological treatment, improved knowledge of usual complications and of their pathophysiology and changes in ICU admission policy and management are among factors which participated to the overall prognostic changes. Tyrosine-Kinase inhibitors in patients with chronic myeloid leukemia and anti-CD20 antibodies in patients with non-hodgkin's lymphoma were among the first success of targeted therapies. These success stories have been followed by others and no less than 13 targeted therapies were available for cancer patients in December 2013. Additionally, pathophysiology of complication is better understood and prognostic impact of organ failure better apprehended. Standardized diagnostic criteria of tumor lysis syndrome along with improved understanding of short-term and long term influence of acute kidney injury (AK) in this setting have led to specific management strategiesfocusing on prevention. In non-malignant haematological diseases, pathophysiological processes leading to thrombotic thrombocytopenic purpura or atypical haemolytic and uremic syndrome are now better understood leading to additional therapeutic options. Last, diversification of ICU admission policies may help in taking into account uncertainties, therapeutic advances and patients' autonomy. This review will give an overview of these recent advances.

[Burn out syndrome among critical care workers]. / Epuisement professionnel en réanimation.

Burnout syndrome (BOS) is a psychological state resulting from prolonged exposure to job stressors. Because intensive care units (ICUs) are characterized by a high level of work-related stress, we reviewed the available literature on BOS among ICU-healthcare workers. Recent studies suggest that severe BOS (measured with the Maslach Burnout Inventory) is present in about half of all critical care physicians and one-third of critical care nurses. Interestingly, the determinants of BOS difer between the two groups of caregivers. Intensivists with severe BOS tend to be those with a large number of working hours (number of night shifts, and time since last vacation), whereas severe BOS among ICU nurses is mainly related to ICU organization and end-of-life care policy. ICU conflicts were independent predictors of severe BOS in both groups. Recent studies also identify potential preventive measures, such as ICU working groups, better communication during end-of-life care, and prevention and management of ICU conflicts.

Austrian validation and customization of the SAPS 3 Admission Score.

OBJECTIVE: To test the prognostic performance of the SAPS 3 Admission Score in a regional cohort and to empirically test the need and feasibility of regional customization. DESIGN: Prospective multicenter cohort study. PATIENTS AND SETTING: Data on a total of 2,060 patients consecutively admitted to 22 intensive care units in Austria from October 2, 2006 to February 28, 2007. MEASUREMENTS AND RESULTS: The database includes basic variables, SAPS 3, length-of-stay and outcome data. The original SAPS 3 Admission Score overestimated hospital mortality in Austrian intensive care patients through all strata of the severity-of-illness. This was true for both available equations, the General and the Central and Western Europe equation. For this reason a customized country-specific model was developed, using cross-validation techniques. This model showed excellent calibration and discrimination in the whole cohort (Hosmer-Lemeshow goodness-of-fit: H = 4.50, P = 0.922; C = 5.61, P = 0.847, aROC, 0.82) as well as in the various tested subgroups. CONCLUSIONS: The SAPS 3 Admission Score's general equation can be seen as a framework for addressing the problem of outcome prediction in the general population of adult ICU patients. For benchmarking purposes, region-specific or country-specific equations seem to be necessary in order to compare ICUs on a similar level.

Outcome prediction in critical care: the Simplified Acute Physiology Score models.

PURPOSE OF REVIEW: Outcome prediction models measuring severity of illness of patients admitted to the intensive care unit should predict hospital mortality. This review describes the state-of-the-art of Simplified Acute Physiology Score models from the clinical and managerial perspectives. Methodological issues concerning the effects of differences between new samples and original databases in which the models were developed are considered. RECENT FINDINGS: The progressive lack of fit of the Simplified Acute Physiology Score II in independent intensive care unit populations induced investigators to propose customizations and expansions as potential evolutions for Simplified Acute Physiology Score II. We do not know whether those solutions did solve the issue because there are no demonstrations of consistent good fit in new databases. The recently developed Simplified Acute Physiology Score 3 Admission Score with customization for geographical areas is discussed. The points shared by the Simplified Acute Physiology Score models and the pros and cons for each of them are introduced. SUMMARY: Comparisons of intensive care unit performance should take into account not only the patient severity of illness, but also the effect of the 'intensive care unit variable', that is, differences in human resources, structure, equipment, management and organization of the intensive care unit. In the future, moving from patient and geographical area adjustment to resource use could allow the user to adjust for differences in healthcare provision.

[Performance of adult intensive care units. Thirty years' experience]. / Comment évaluer la performance d'un service de réanimation d'adultes? Une expérience de 30 ans.

ICU performance can be evaluated by using the standard mortality ratio (SMR), but the points of view of the patients, families, and medical and non medical staff must also be taken in account. The SMR is the ratio between the observed (O) and predicted hospital mortality rates (P), based on a statistical model. If for 100 consecutive unselected patients the O/P ratio is less than 1, then the performance is considered good, and otherwise as bad. Most studies show good post-ICU quality of life. Management of dying patients in the ICU is an important issue. Families are stressed, both during and after the ICU stay, and they often have signs of anxiety and depression. It is illogical to involve them in hard decisions such as halting active therapy. Medical and non medical staff are also under pressure and may suffer from the burn-out syndrome. Causes include conflicts among doctors, or between doctors and nurses. There is a close relationship between ICU organisation and performance: good management makes for high performance.

Time course of organ dysfunction in thrombotic microangiopathy patients receiving either plasma perfusion or plasma exchange.

INTRODUCTION: Few studies have investigated adults with thrombotic microangiopathy (TMA) requiring intensive care unit (ICU) admission, and the treatment remains controversial. OBJECTIVE: To describe causes, outcomes, prognostic factors, and daily organ-failure score changes in adults with TMA requiring ICU admission. DESIGN: A 3-yr single-center cohort study. PATIENTS: The patients were 36 adults with TMA admitted to a teaching-hospital medical ICU between January 2000 and June 2003. RESULTS: Of the 36 patients, 22 received plasma infusion and 15 underwent plasma exchange. All patients had anemia and thrombocytopenia at ICU admission, and 13 had neurologic impairment. Median creatinine clearance was 55.2 mL/min (interquartile range, 28.8-75.4). No patient had congenital TMA. Causative factors included microbiologically documented infection in 14 patients, allogeneic transplantation in 7 patients, and concomitant or subsequent systemic disease in 7 patients; 6 patients were human immunodeficiency virus-positive, 5 had drug-induced TMA, 2 were pregnant, and 2 had cancer. In 10 patients, no causative factors were identified. Plasma exchange was associated with a statistically significant decrease in hospital mortality (0 vs. 7 deaths; p < .001). Moreover, daily organ-failure scores were significantly lower in the plasma-exchange group from day 3 to day 9. Patients in the plasma-exchange group received a larger volume of plasma. CONCLUSION: Plasma exchange may be associated with faster resolution of organ failure and with improved survival for patients with TMA requiring ICU admission.

An evaluation of systemic inflammatory response syndrome signs in the Sepsis Occurrence In Acutely Ill Patients (SOAP) study.

OBJECTIVE: To define the frequency and prognostic implications of SIRS criteria in critically ill patients hospitalized in European ICUs. DESIGN AND SETTING: Cohort, multicentre, observational study of 198 ICUs in 24 European countries. PATIENTS AND INTERVENTIONS: All 3,147 new adult admissions to participating ICUs between 1 and 15 May 2002 were included. Data were collected prospectively, with common SIRS criteria. RESULTS: During the ICU stay 93% of patients had at least two SIRS criteria [respiratory rate (82%), heart rate (80%)]. The frequency of having three or four SIRS criteria vs. two was higher in infected than non-infected patients (p < 0.01). In non-infected patients having more than two SIRS criteria was associated with a higher risk of subsequent development of severe sepsis (odds ratio 2.6, p < 0.01) and septic shock (odds ratio 3.7, p < 0.01). Organ system failure and mortality increased as the number of SIRS criteria increased. CONCLUSIONS: Although common in the ICU, SIRS has prognostic importance in predicting infections, severity of disease, organ failure and outcome.

Sepsis in European intensive care units: results of the SOAP study.

OBJECTIVE: To better define the incidence of sepsis and the characteristics of critically ill patients in European intensive care units. DESIGN: Cohort, multiple-center, observational study. SETTING: One hundred and ninety-eight intensive care units in 24 European countries. PATIENTS: All new adult admissions to a participating intensive care unit between May 1 and 15, 2002. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Demographic data, comorbid diseases, and clinical and laboratory data were collected prospectively. Patients were followed up until death, until hospital discharge, or for 60 days. Of 3,147 adult patients, with a median age of 64 yrs, 1,177 (37.4%) had sepsis; 777 (24.7%) of these patients had sepsis on admission. In patients with sepsis, the lung was the most common site of infection (68%), followed by the abdomen (22%). Cultures were positive in 60% of the patients with sepsis. The most common organisms were Staphylococcus aureus (30%, including 14% methicillin-resistant), Pseudomonas species (14%), and Escherichia coli (13%). Pseudomonas species was the only microorganism independently associated with increased mortality rates. Patients with sepsis had more severe organ dysfunction, longer intensive care unit and hospital lengths of stay, and higher mortality rate than patients without sepsis. In patients with sepsis, age, positive fluid balance, septic shock, cancer, and medical admission were the important prognostic variables for intensive care unit mortality. There was considerable variation between countries, with a strong correlation between the frequency of sepsis and the intensive care unit mortality rates in each of these countries. CONCLUSIONS: This large pan-European study documents the high frequency of sepsis in critically ill patients and shows a close relationship between the proportion of patients with sepsis and the intensive care unit mortality in the various countries. In addition to age, a positive fluid balance was among the strongest prognostic factors for death. Patients with intensive care unit acquired sepsis have a worse outcome despite similar severity scores on intensive care unit admission.

Mortality prediction using SAPS II: an update for French intensive care units.

INTRODUCTION: The standardized mortality ratio (SMR) is commonly used for benchmarking intensive care units (ICUs). Available mortality prediction models are outdated and must be adapted to current populations of interest. The objective of this study was to improve the Simplified Acute Physiology Score (SAPS) II for mortality prediction in ICUs, thereby improving SMR estimates. METHOD: A retrospective data base study was conducted in patients hospitalized in 106 French ICUs between 1 January 1998 and 31 December 1999. A total of 77,490 evaluable admissions were split into a training set and a validation set. Calibration and discrimination were determined for the original SAPS II, a customized SAPS II and an expanded SAPS II developed in the training set by adding six admission variables: age, sex, length of pre-ICU hospital stay, patient location before ICU, clinical category and whether drug overdose was present. The training set was used for internal validation and the validation set for external validation. RESULTS: With the original SAPS II calibration was poor, with marked underestimation of observed mortality, whereas discrimination was good (area under the receiver operating characteristic curve 0.858). Customization improved calibration but had poor uniformity of fit; discrimination was unchanged. The expanded SAPS II exhibited good calibration, good uniformity of fit and better discrimination (area under the receiver operating characteristic curve 0.879). The SMR in the validation set was 1.007 (confidence interval 0.985-1.028). Some ICUs had better and others worse performance with the expanded SAPS II than with the customized SAPS II. CONCLUSION: The original SAPS II model did not perform sufficiently well to be useful for benchmarking in France. Customization improved the statistical qualities of the model but gave poor uniformity of fit. Adding simple variables to create an expanded SAPS II model led to better calibration, discrimination and uniformity of fit, producing a tool suitable for benchmarking.

Intensive care in patients with newly diagnosed malignancies and a need for cancer chemotherapy.

OBJECTIVE: Patients with newly diagnosed cancer responsible for organ failures may require intensive care unit (ICU) admission and immediate chemotherapy. Outcomes in this population have not been studied. DESIGN: Prospective observational cohort study. SETTING: Teaching hospital. SUBJECTS: All patients admitted to the ICU, from January 1997 to June 2003, for organ failures due to newly diagnosed, untreated cancer and deemed necessary to receive immediate cancer chemotherapy. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: For the period of 6.5 yrs, 100 patients met the study criteria: 43 had acute leukemia, 37 lymphoma, and 12 solid tumors. Median Simplified Acute Physiology Score II was 39 (30-48) points, and median Logistic Organ Dysfunction score was 5 (3-7) points. Three variables were independently associated with 30-day mortality: need for vasopressor therapy (odds ratio, 6.01; 95% confidence interval, 1.86-19.4), mechanical ventilation (odds ratio, 6.36; 95% confidence interval, 1.76-22.94); and hepatic failure (odds ratio, 7.76; 95% confidence interval, 1.25-48.27). Overall survival was 60% after 30 days and 49% after 180 days. CONCLUSIONS: Mortality was chiefly dependent on the nature and number of organ failures, not on the nature or stage of the malignancy. The 30-day and 180-day survival rates indicate that, in this selected group of patients, advanced disease at cancer diagnosis should not lead to refusal of ICU admission. Moreover, administration of chemotherapy in the intensive care unit is feasible, and although the mortality rate is high, routine ICU admission of patients with newly diagnosed cancer, specific organ failure, and the need for administration of chemotherapy in the ICU deserves evaluation.

SAPS 3--From evaluation of the patient to evaluation of the intensive care unit. Part 2: Development of a prognostic model for hospital mortality at ICU admission.

OBJECTIVE: To develop a model to assess severity of illness and predict vital status at hospital discharge based on ICU admission data. DESIGN: Prospective multicentre, multinational cohort study. PATIENTS AND SETTING: A total of 16,784 patients consecutively admitted to 303 intensive care units from 14 October to 15 December 2002. MEASUREMENTS AND RESULTS: ICU admission data (recorded within +/-1 h) were used, describing: prior chronic conditions and diseases; circumstances related to and physiologic derangement at ICU admission. Selection of variables for inclusion into the model used different complementary strategies. For cross-validation, the model-building procedure was run five times, using randomly selected four fifths of the sample as a development- and the remaining fifth as validation-set. Logistic regression methods were then used to reduce complexity of the model. Final estimates of regression coefficients were determined by use of multilevel logistic regression. Variables selection and weighting were further checked by bootstraping (at patient level and at ICU level). Twenty variables were selected for the final model, which exhibited good discrimination (aROC curve 0.848), without major differences across patient typologies. Calibration was also satisfactory (Hosmer-Lemeshow goodness-of-fit test H=10.56, p=0.39, C=14.29, p=0.16). Customized equations for major areas of the world were computed and demonstrate a good overall goodness-of-fit. CONCLUSIONS: The SAPS 3 admission score is able to predict vital status at hospital discharge with use of data recorded at ICU admission. Furthermore, SAPS 3 conceptually dissociates evaluation of the individual patient from evaluation of the ICU and thus allows them to be assessed at their respective reference levels.

SAPS 3--From evaluation of the patient to evaluation of the intensive care unit. Part 1: Objectives, methods and cohort description.

OBJECTIVE: Risk adjustment systems now in use were developed more than a decade ago and lack prognostic performance. Objective of the SAPS 3 study was to collect data about risk factors and outcomes in a heterogeneous cohort of intensive care unit (ICU) patients, in order to develop a new, improved model for risk adjustment. DESIGN: Prospective multicentre, multinational cohort study. PATIENTS AND SETTING: A total of 19,577 patients consecutively admitted to 307 ICUs from 14 October to 15 December 2002. MEASUREMENTS AND RESULTS: Data were collected at ICU admission, on days 1, 2 and 3, and the last day of the ICU stay. Data included sociodemographics, chronic conditions, diagnostic information, physiological derangement at ICU admission, number and severity of organ dysfunctions, length of ICU and hospital stay, and vital status at ICU and hospital discharge. Data reliability was tested with use of kappa statistics and intraclass-correlation coefficients, which were >0.85 for the majority of variables. Completeness of the data was also satisfactory, with 1 [0-3] SAPS II parameter missing per patient. Prognostic performance of the SAPS II was poor, with significant differences between observed and expected mortality rates for the overall cohort and four (of seven) defined regions, and poor calibration for most tested subgroups. CONCLUSIONS: The SAPS 3 study was able to provide a high-quality multinational database, reflecting heterogeneity of current ICU case-mix and typology. The poor performance of SAPS II in this cohort underscores the need for development of a new risk adjustment system for critically ill patients.

Outcome of cancer patients considered for intensive care unit admission: a hospital-wide prospective study.

PURPOSE: To evaluate the outcome of cancer patients considered for admission to the intensive care unit (ICU). PATIENTS AND METHODS: Prospective, one-year hospital-wide study of all cancer and hematology patients, including bone marrow transplantation patients, for whom admission to the ICU was requested. RESULTS: Of the 206 patients considered for ICU admission, 105 patients (51%) were admitted. Of the 101 patients who were not admitted, 54 patients (26.2%) were considered too sick to benefit, and 47 patients (22.8%) were considered to be too well to benefit from the ICU. Of these 47 patients, 13 patients were admitted later. Survival rates after 30 and 180 days were significantly associated with admission status (P < .0001). Remission of the malignancy (odds ratio [OR], 3.37; 95% CI, 1.25 to 9.07) was independently associated with ICU admission, whereas poor chronic health status (OR, 0.38; 95% CI, 0.16 to 0.74) and solid tumor (OR, 0.43; 95% CI, 0.24 to 0.78) were associated with ICU refusal. In admitted patients, 30-day and 6-month survival rates were 54.3% and 32.4%, respectively. Of the patients considered too sick to benefit from ICU admission, 26% were alive on day 30 and 16.7% on day 180. Among patients considered too well to benefit, the 30-day survival rate was a worrisome 78.7%. Calibration of the Mortality Probability Model (the only score available at triage) was of limited value for predicting 30-day survival (area under the curve, 0.62). CONCLUSION: Both the excess mortality in too-well patients later admitted to the ICU and the relatively good survival in too-sick patients suggest the need for a broader admission policy.

Post-ICU mortality in critically ill infected patients: an international study.

OBJECTIVE: To determine the incidence and risk factors for post-ICU mortality in patients with infection. DESIGN AND SETTING: International observational cohort study including 28 ICUs in eight countries. PATIENTS: All 1,872 patients discharged alive from the ICU over a 1-year period were screened for infection at ICU admission and daily throughout the ICU stay. Outcomes at ICU and hospital discharge were recorded. MEASUREMENTS AND RESULTS: Post-ICU death occurred in 195 (10.4%) patients and was associated in the multivariable analysis with age, chronic respiratory failure, immunosuppression, cirrhosis, Simplified Acute Physiology Score II on the first day with infection, and LOD score at ICU discharge. Post-ICU death was more common among medical patients and patients with hospital-acquired infection or microbiologically documented infection and was less common in patients with pneumonia. CONCLUSIONS: Post-ICU death in patients with infection was within previously reported ranges in overall ICU populations. The main risk factors were patient and infection characteristics, severity at ICU admission, and persistent organ dysfunction at ICU discharge. Further interventions such as further ICU management, discharge to a step-down unit, or follow-up by intensivists on the ward should be evaluated in patients with a high risk of post-ICU mortality.

Systemic inflammatory response and progression to severe sepsis in critically ill infected patients.

RATIONALE: The systemic inflammatory response syndrome has low specificity to identify infected patients at risk of worsening to severe sepsis or shock. OBJECTIVE: To examine the incidence of and risk factors for worsening sepsis in infected patients. METHODS: A 1-year inception cohort study in 28 intensive care units of patients (n = 1,531) having a first episode of infection on admission or during the stay. MEASUREMENTS AND MAIN RESULTS: The cumulative incidence of progression to severe sepsis or shock was 20% and 24% at Days 10 and 30, respectively. Variables independently associated (hazard ratio [HR]) with worsening sepsis included: temperature higher than 38.2 degrees C (1.6), heart rate greater than 120/minute (1.3), systolic blood pressure higher than 110 mm Hg (1.5), platelets higher than 150 x 109/L (1.5), serum sodium higher than 145 mmol/L (1.5), bilirubin higher than 30 mumol/L (1.3), mechanical ventilation (1.5), and five variables characterizing infection (pneumonia [HR 1.5], peritonitis [1.5], primary bacteremia [1.8], and infection with gram-positive cocci [1.3] or aerobic gram-negative bacilli [1.4]). The 12 weighted variables were included in a score (Risk of Infection to Severe Sepsis and Shock Score, range 0-49), summarized in four classes of "low" (score 0-8) and "moderate" (8.5-16) risk (9% and 17% probability of worsening, respectively), and of "high" (16.5-24) and "very high" (score > 24) risk (31% and 55% probability, respectively). CONCLUSIONS: One of four patients presenting with infection/sepsis worsen to severe sepsis or shock. A score estimating this risk, using objectively defined criteria for systemic inflammatory response syndrome, could be used by physicians to stratify patients for clinical management and to test new interventions.

The prognosis of acute respiratory failure in critically ill cancer patients.

Acute respiratory failure (ARF) in patients with cancer is frequently a fatal event. To identify factors associated with survival of cancer patients admitted to an intensive care unit (ICU) for ARF, we conducted a prospective 5-year observational study in a medical ICU in a teaching hospital in Paris, France. The patients were 203 cancer patients with ARF mainly due to infectious pneumonia (58%), but also noninfectious pneumonia (9%), congestive heart failure (12%), and no identifiable cause (21%). We measured clinical characteristics and ICU and hospital mortality rates.ICU mortality was 44.8% and hospital mortality was 47.8%. Noninvasive mechanical ventilation was used in 79 (39%) patients and conventional mechanical ventilation in 114 (56%), the mortality rates being 48.1% and 75.4%, respectively. Among the 14 patients with late noninvasive mechanical ventilation failure (>48 hours), only 1 survived. The mortality rate was 100% in the 19 noncardiac patients in whom conventional mechanical ventilation was started after 72 hours. By multivariable analysis, factors associated with increased mortality were documented invasive aspergillosis (odds ratio [OR], 2.13; 95% confidence intervals [CI], 1.05-14.74), no definite diagnosis (OR, 3.85; 95% CI, 1.26-11.70), vasopressors (OR, 3.19; 95% CI, 1.28-7.95), first-line conventional mechanical ventilation (OR, 8.75; 95% CI, 2.35-35.24), conventional mechanical ventilation after noninvasive mechanical ventilation failure (OR, 17.46; 95% CI, 5.04-60.52), and late noninvasive mechanical ventilation failure (OR, 10.64; 95% CI, 1.05-107.83). Hospital mortality was lower in patients with cardiac pulmonary edema (OR, 0.16; 95% CI, 0.03-0.72). Survival gains achieved in critically ill cancer patients in recent years extend to patients requiring ventilatory assistance. The impact of conventional mechanical ventilation on survival depends on the time from ICU admission to conventional mechanical ventilation and on the patient's response to noninvasive mechanical ventilation.

Measuring performance in health care: case-mix adjustment by boosted decision trees.

OBJECTIVE: The purpose of this paper is to investigate the suitability of boosted decision trees for the case-mix adjustment involved in comparing the performance of various health care entities. METHODS: First, we present logistic regression, decision trees, and boosted decision trees in a unified framework. Second, we study in detail their application for two common performance indicators, the mortality rate in intensive care and the rate of potentially avoidable hospital readmissions. RESULTS: For both examples the technique of boosting decision trees outperformed standard prognostic models, in particular linear logistic regression models, with regard to predictive power. On the other hand, boosting decision trees was computationally demanding and the resulting models were rather complex and needed additional tools for interpretation. CONCLUSION: Boosting decision trees represents a powerful tool for case-mix adjustment in health care performance measurement. Depending on the specific priorities set in each context, the gain in predictive power might compensate for the inconvenience in the use of boosted decision trees.

Half the family members of intensive care unit patients do not want to share in the decision-making process: a study in 78 French intensive care units.

OBJECTIVE: To evaluate the opinions of intensive care unit staff and family members about family participation in decisions about patients in intensive care units in France, a country where the approach of physicians to patients and families has been described as paternalistic. DESIGN: Prospective multiple-center survey of intensive care unit staff and family members. SETTING: Seventy-eight intensive care units in university-affiliated hospitals in France. PATIENTS: We studied 357 consecutive patients hospitalized in the 78 intensive care units and included in the study starting on May 1, 2001, with five patients included per intensive care unit. INTERVENTIONS: We recorded opinions and experience about family participation in medical decision making. Comprehension, satisfaction, and Hospital Anxiety and Depression Scale scores were determined in family members. MEASUREMENTS AND MAIN RESULTS: Poor comprehension was noted in 35% of family members. Satisfaction was good but anxiety was noted in 73% and depression in 35% of family members. Among intensive care unit staff members, 91% of physicians and 83% of nonphysicians believed that participation in decision making should be offered to families; however, only 39% had actually involved family members in decisions. A desire to share in decision making was expressed by only 47% of family members. Only 15% of family members actually shared in decision making. Effectiveness of information influenced this desire. CONCLUSION: Intensive care unit staff should seek to determine how much autonomy families want. Staff members must strive to identify practical and psychological obstacles that may limit their ability to promote autonomy. Finally, they must develop interventions and attitudes capable of empowering families.

Cardiovascular effects of the nitric oxide synthase inhibitor NG-methyl-L-arginine hydrochloride (546C88) in patients with septic shock: results of a randomized, double-blind, placebo-controlled multicenter study (study no. 144-002).

OBJECTIVE: To assess the hemodynamic effects of the nitric oxide synthase inhibitor 546C88 in patients with septic shock, although this was not a stated aim of the protocol. The predefined primary efficacy objective of the protocol was resolution of shock determined at the end of a 72-hr treatment period. DESIGN: Multicentered, randomized, placebo-controlled, safety and efficacy study. SETTING: Forty-eight intensive care units in Europe, North America, and Australia. PATIENTS: A total of 312 patients with septic shock diagnosed within 24 hr before randomization. INTERVENTIONS: Patients were randomly allocated to receive either 546C88 or placebo (5% dextrose) by intravenous infusion for up to 72 hrs. Conventional vasoactive therapy was restricted to norepinephrine, dopamine, and dobutamine. Study drug was initiated at 0.1 mL/kg/hr (5 mg/kg/hr 546C88) and titrated according to response up to a maximum rate of 0.4 mL/kg/hr with the objective to maintain mean arterial pressure at 70 mm Hg while attempting to withdraw any concurrent vasopressor(s). MEASUREMENTS AND MAIN RESULTS: Requirement for vasopressors, systemic and pulmonary hemodynamics, indices of oxygen transport, and plasma concentrations of arginine and nitrate were assessed over time. The median mean arterial pressure for both groups was maintained > or =70 mm Hg. There was an early increase in systemic and pulmonary vascular tone and oxygen extraction, whereas both cardiac index and oxygen delivery decreased for patients in the 546C88 cohort. Although these parameters subsequently returned toward baseline values, the observed differences between the treatment groups, except for pulmonary vascular resistance and oxygen extraction, persisted throughout the treatment period, despite a reduced requirement for vasopressors in the 546C88 cohort. These changes were associated with a reduction in plasma nitrate concentrations, which were elevated in both groups before the start of therapy. CONCLUSIONS: The nitric oxide synthase inhibitor 546C88 can reduce the elevated plasma nitrate concentrations observed in patients with septic shock. In this study, treatment with 546C88 for up to 72 hrs was associated with an increase in vascular tone and a reduction in both cardiac index and oxygen delivery. The successful maintenance of a target mean arterial blood pressure > or =70 mm Hg was achieved with a reduction in the requirement for, or withdrawal of, conventional inotropic vasoconstrictor agents (i.e., dopamine and norepinephrine). There were no substantive untoward consequences accompanying these hemodynamic effects. An international, randomized, double-blind, placebo-controlled phase III study has since been conducted in patients with septic shock. Recruitment into the study was discontinued due to the emergence of increased mortality in the 546C88-treated group.