Showing papers by "Gordon R. Bernard published in 2004"

Delirium as a predictor of mortality in mechanically ventilated patients in the intensive care unit

Abstract: ContextIn the intensive care unit (ICU), delirium is a common yet underdiagnosed form of organ dysfunction, and its contribution to patient outcomes is unclear.ObjectiveTo determine if delirium is an independent predictor of clinical outcomes, including 6-month mortality and length of stay among ICU patients receiving mechanical ventilation.Design, Setting, and ParticipantsProspective cohort study enrolling 275 consecutive mechanically ventilated patients admitted to adult medical and coronary ICUs of a US university-based medical center between February 2000 and May 2001. Patients were followed up for development of delirium over 2158 ICU days using the Confusion Assessment Method for the ICU and the Richmond Agitation-Sedation Scale.Main Outcome MeasuresPrimary outcomes included 6-month mortality, overall hospital length of stay, and length of stay in the post-ICU period. Secondary outcomes were ventilator-free days and cognitive impairment at hospital discharge.ResultsOf 275 patients, 51 (18.5%) had persistent coma and died in the hospital. Among the remaining 224 patients, 183 (81.7%) developed delirium at some point during the ICU stay. Baseline demographics including age, comorbidity scores, dementia scores, activities of daily living, severity of illness, and admission diagnoses were similar between those with and without delirium (P>.05 for all). Patients who developed delirium had higher 6-month mortality rates (34% vs 15%, P = .03) and spent 10 days longer in the hospital than those who never developed delirium (P<.001). After adjusting for covariates (including age, severity of illness, comorbid conditions, coma, and use of sedatives or analgesic medications), delirium was independently associated with higher 6-month mortality (adjusted hazard ratio [HR], 3.2; 95% confidence interval [CI], 1.4-7.7; P = .008), and longer hospital stay (adjusted HR, 2.0; 95% CI, 1.4-3.0; P<.001). Delirium in the ICU was also independently associated with a longer post-ICU stay (adjusted HR, 1.6; 95% CI, 1.2-2.3; P = .009), fewer median days alive and without mechanical ventilation (19 [interquartile range, 4-23] vs 24 [19-26]; adjusted P = .03), and a higher incidence of cognitive impairment at hospital discharge (adjusted HR, 9.1; 95% CI, 2.3-35.3; P = .002).ConclusionDelirium was an independent predictor of higher 6-month mortality and longer hospital stay even after adjusting for relevant covariates including coma, sedatives, and analgesics in patients receiving mechanical ventilation.

Costs associated with delirium in mechanically ventilated patients.

Abstract: ObjectiveTo determine the costs associated with delirium in mechanically ventilated medical intensive care unit patients.DesignProspective cohort study.SettingA tertiary care academic hospital.PatientsPatients were 275 consecutive mechanically ventilated medical intensive care unit patients.Interven

Current opinions regarding the importance, diagnosis, and management of delirium in the intensive care unit: a survey of 912 healthcare professionals.

Abstract: Objective: Recently published clinical practice guidelines of the Society of Critical Care Medicine recommend monitoring for the presence of delirium in all mechanically ventilated patients because of the potential for adverse outcomes associated with this comorbidity, yet little is known about healthcare professionals’ opinions regarding intensive care unit delirium or how they manage this organ dysfunction. The aim of this survey was to assess the medical community’s beliefs and practices regarding delirium in the intensive care unit. Design: Survey administration was conducted both without a delirium definition (phase 1) and then with a definition of delirium (phase 2). Setting: Critical care meetings and continuing medical education/ board review courses from October 2001 to July 2002 Participants: A convenience sample of physicians (n 753), nurses (n 113), pharmacists (n 13), physician assistants (n 12), respiratory care practitioners (n 8), and others (n 13). Interventions: Survey. Measurements and Main Results: Participants completed 912 of the surveys. The majority (68%) of respondents thought that >25% of adult mechanically ventilated patients experience delirium. Delirium was considered a significant or very serious problem in the intensive care unit by 92% of healthcare professionals, yet underdiagnosis was acknowledged by 78%. Only 40% reported routinely screening for delirium, and only 16% indicated using a specific tool for delirium assessment. Delirium was considered important in the outcome of elderly and young patients by 89% and 60% of the respondents, respectively (p 50 mg/day of either medication. Conclusions: Most healthcare professionals consider delirium in the intensive care unit a common and serious problem, although few actually monitor for this condition and most admit that it is underdiagnosed. Data from this survey point to a disconnect between the perceived significance of delirium in the intensive care unit and current practices of monitoring and treatment. (Crit Care Med 2004; 32:106 –112)

Neutrophil elastase inhibition in acute lung injury: results of the STRIVE study

Abstract: Objective:Neutrophil elastase is believed to be an important mediator of acute lung injury. Sivelestat (ONO-5046, Elaspol) is a small molecular weight inhibitor of neutrophil elastase. The primary objectives of this study were to determine whether sivelestat would reduce 28-day all-cause mortality o

Albumin influences total plasma antioxidant capacity favorably in patients with acute lung injury.

Abstract: Objective: To ascertain the influence of albumin on antioxidant status in patients with acute lung injury. Design: Prospective, randomized, placebo-controlled study. Setting: Intensive care units, teaching hospitals. Patients: Twenty patients meeting the American European Consensus criteria for acute lung injury. Interventions: Ten patients received albumin (25 g of a 25% solution every 8 hrs for a total of nine doses) and ten received placebo (normal saline administered in identical fashion and volume). All received supportive therapy appropriate for patients with acute lung injury. Plasma samples were obtained sequentially from all patients before, 30 mins after, and 4 hrs after albumin/placebo administration. Measurements and Main Results: Serum albumin and total protein, total antioxidant status, iron-binding antioxidant protection, iron-oxidizing antioxidant protection, lipid hydroperoxides, protein carbonyls, and plasma thiols were measured. Albumin administration increased plasma albumin concentrations (p <.05 compared with placebo) and decreased concentrations of protein carbonyls (p <.05 compared with placebo). By contrast, plasma lipid hydroperoxide concentrations were similar in both groups, both in absolute terms and relative to albumin content. For all other variables, no significant differences were apparent. For all patients, there was a positive correlation between albumin and plasma thiol concentrations (r =.983, p <.01) and albumin and antioxidant capacity (r =.885, p =.01). In the albumin treatment group, there was a strong correlation between thiols and antioxidant capacity (r =.876, p =.01). No such correlation was apparent in the placebo group. Plasma iron-binding antioxidant protection was negatively correlated (r = -.741, p <.05) with albumin content in the treatment group but not the placebo group. Conclusions: In patients with acute lung injury, albumin administration favorably influences plasma thiol-dependent antioxidant status as well as levels of protein oxidative damage.

The effect of drotrecogin alfa (activated) on long-term survival after severe sepsis.

Abstract: Objective:To determine long-term survival for subjects with severe sepsis enrolled in the previous multiple-center trial (PROWESS) of drotrecogin alfa (activated) (DrotAA) vs. placebo.Design:Retrospective, cross-sectional, blinded follow-up of subjects enrolled in a previous randomized, controlled t

Consciousness monitoring in ventilated patients: bispectral EEG monitors arousal not delirium.

Abstract: Objective Bispectral index (BIS) is being evaluated as a monitor of consciousness, yet it is unclear what components of consciousness (i.e., arousal vs. content of consciousness) the BIS measures. This study compared BIS levels to well-validated clinical measures of arousal and the presence or absence of delirium.

Sources of variability on the estimate of treatment effect in the PROWESS trial: implications for the design and conduct of future studies in severe sepsis.

Abstract: Objective. To elucidate sources of variability in the estimate of treatment effects in a successful phase 3 trial in severe sepsis and to assess their implications on the design of future clinical trials. Design. Retrospective evaluation of prospectively defined subgroups from a large phase 3, placebo-controlled clinical trial (PROWESS). Setting. The study involved 164 medical centers. Patients: Patients were 1,690 patients with severe sepsis. Interventions. Drotrecogin alfa (activated) (Xigris) 24 mug/kg/hr for 96 hrs, or placebo. Measurements and Main Results: All prospectively defined subgroups were examined to identify treatment effects that potentially differed across subgroup strata (assessed by Breslow-Day p < .10). Potential interactions were identified for subgroups defined by a) presence vs. absence of a significant protocol violation (p = .07); b) original vs. amended protocol (p = .08); and c) Acute Physiology and Chronic Health Evaluation (APACHE) II quartile at baseline (P = .09). No treatment benefit was observed in patients having a protocol violation, regardless of type. There appeared to be less treatment effect in patients enrolled under the original vs. amended protocol. The risk ratio exceeded 1.0 for patients in the lowest APACHE II score quartile. A highly significant correlation was observed between the sequence of enrollment at a site, the frequency of protocol violations, and the observed treatment effect. As enrollment increased, frequency of protocol violations decreased (p < .0001) and the treatment effect improved. The correlation between the sequence of enrollment and improvement in treatment effect remained even after removal of patients with protocol violations. Removal of the first block of patents at each site from the analysis reduced the extent of interaction by protocol version and APACHE II score. Conclusions. A learning curve appeared to be present within the PROWESS trial such that the ability to demonstrate efficacy improved with increasing site experience. This potential learning curve may have implications for design of future trials. Investigational sites may need to require a minimum level of protocol-specific experience to appropriately implement a given trial. This experience should be an important consideration in designing trials and analysis plans. Diligence by coordinating centers, site investigators, study coordinators, and sponsors is necessary to ensure that the protocol is executed as designed such that a treatment benefit, if present, will be evident.

Noninvasive Ventilation — Don't Push Too Hard

Abstract: Noninvasive mechanical ventilation has been used increasingly over the past decade in an effort to avoid endotracheal intubation and to accelerate the discontinuation of mechanical ventilation. Noninvasive ventilation as adjunctive therapy can be applied before intubation or after extubation (Figure 1). The literature indicates that in both settings, outcomes in patients with chronic obstructive pulmonary disease (COPD) or cardiogenic pulmonary edema are successful.1 Randomized, controlled trials also provide outcome data supporting the use of noninvasive ventilation to obviate the need for endotracheal intubation in immunosuppressed patients who have bilateral infiltrates and patients who are recovering from lung resection.1 Noninvasive ventilation . . .

Advances in Sepsis Treatment.

Abstract: Investigations of novel sepsis treatments have proven ineffective in the past. Despite advances in overall care of critically ill patients, therapies specifically designated for sepsis were lacking. However, research unveiled a complex interaction between the coagulation and inflammation systems, which has served as an impetus for innovative pharmacologic therapies in the treatment of patients with sepsis. This article summarizes the results of trials involving drotrecogin alfa (activated), or recombinant human activated protein C, the only medicine currently approved by the US Food and Drug Administration for the treatment of severe sepsis. In addition, the beneficial effects of early, goal-directed resuscitation, guided by continuous central venous oxygen saturations, are discussed, with the issues involved in the use of corticosteroids in a subset of patients with septic shock. This article also reviews the beneficial effects of tight glycemic control in postoperative critically ill patients and considers whether the data can be extrapolated to medical patients.

New additions to the intensive care armamentarium

Abstract: Many advances have improved the care of critically ill patients, but only a few have been through the use of pharmaceutical agents. Recently, the US Food and Drug Administration (FDA) approved drotrecogin alfa (activated), or recombinant human activated protein C, for the treatment of patients with a high risk of death from severe sepsis. Drotrecogin alfa (activated) has antiinflammatory, antithrombotic and fibrinolytic properties. When given as a continuous intravenous infusion, recombinant human activated protein C decreases absolute mortality of severely septic patients by 6.1%, resulting in a 19.4% relative reduction in mortality. The absolute reduction in mortality increases to 13% if the population treated is restricted to patients with an APACHE II score greater than 24, as suggested by the FDA. The most frequent and serious side effect is bleeding. Severe bleeds increased from 2% in patients given placebo to 3.5% in patients receiving drotrecogin alfa (activated). The risk of bleeding was only increased during the actual infusion time of the drug, and the bleeding risk returned to placebo levels 24 hours after the infusion was discontinued. Patients treated in the intensive care unit frequently develop anemia, usually severe enough to require at least one transfusion of red blood cells. With the recent discovery of the harmful effects of allogeneic red blood cell transfusions and the increasing shortage of available red blood cell products, emphasis has been placed on minimizing transfusions. Patients who receive exogenous recombinant human erythropoietin maintain higher hemoglobin levels, in spite of requiring fewer transfusions during their stay in the intensive care unit. Recombinant human erythropoietin appears to be effective whether it is given as 300 units/kg of body weight subcutaneously every other day or as 40,000 units subcutaneously every week. Differences in hemoglobin values were not apparent until at least one week of therapy, but they continued to diverge after that initial week. Furthermore, the incidence of adverse events was similar to that of patients receiving placebo and there was no difference in mortality, suggesting that avoidance of blood transfusions did not translate into increased survival. Thus, recombinant human erythropoietin appears to be both safe and effective in treating the anemia found in critically ill patients, but it is less clear that such treatment is cost effective, especially in the higher dose regimens. Hypotension in patients with septic shock is often difficult to correct. Despite enormous dosages of catecholamines, many of these patients continue to have inadequate blood pressures. Inadequate levels of vasopressin have been identified in patients with septic shock, as well as in other patients with hypotension secondary to refractory vasodilatation. Vasopressin is a peptide hormone secreted from the posterior pituitary in response to hyperosmolality, hypovolemia or hypotension. Levels of vasopressin initially rise in patients with septic shock, but as hypotension persists, vasopressin levels fall below normal. Administration of exogenous vasopressin in physiologic dosages significantly increases blood pressure in patients with shock associated with sepsis and other vasodilatory states. This rise in blood pressure is often significant enough that endogenous catecholamines can be decreased and frequently discontinued entirely. Early withdrawal of the vasopressin replacement infusion results in recurrent hypotension. Unfortunately, randomized, blinded, placebo-controlled trials showing improvement in long-term outcomes such as mortality and length of stay are still lacking.