Miriam M. Treggiari

Randomized trial of light versus deep sedation on mental health after critical illness

Objectives:To investigate if light sedation favorably affects subsequent patient mental health compared with deep sedation. Symptoms of posttraumatic stress disorder are common in patients after they have undergone prolonged mechanical ventilation and are associated with sedation depth. Design:Randomized, open-label, controlled trial. Setting:Single tertiary care center. Patients:Adult patients requiring mechanical ventilation. Interventions:Patients were randomized to receive either light (patient awake and cooperative) or deep sedation (patient asleep, awakening upon physical stimulation). Measurements and Main Results:Self-reported measures of posttraumatic stress disorder, anxiety, and depression were collected at intensive care unit discharge and 4 wks later. The primary outcomes were symptoms of posttraumatic stress disorder, anxiety, and depression 4 wks after intensive care unit discharge. A total of 137 patients were assigned to either the light (n = 69) or the deep sedation (n = 68) group. Seven patients withdrew consent and one patient was randomized in error, leaving 129 patients (n = 65 in light sedation and n = 64 in deep sedation) available for analysis. At the 4-wk follow-up, patients in the deep sedation group tended to have more posttraumatic stress disorder symptoms (p = .07); the deep sedation group had more trouble remembering the event (37% vs. 14%; p = .02) and more disturbing memories of the intensive care unit (18% vs. 4%; p = .05). Patients in the light sedation group had an average one day less being ventilated and 1.5 fewer days in the intensive care unit. There were no differences between the two groups in the occurrence of anxiety and depression, and also no difference in mortality or in the incidence of adverse events. Conclusions:These data suggest that a strategy of light sedation affords benefits with regard to reduction of intensive care unit stay and duration of ventilation without negatively affecting subsequent patient mental health or patient safety.

Intensive insulin therapy and mortality in critically ill patients.

IntroductionIntensive insulin therapy (IIT) with tight glycemic control may reduce mortality and morbidity in critically ill patients and has been widely adopted in practice throughout the world. However, there is only one randomized controlled trial showing unequivocal benefit to this approach and that study population was dominated by post-cardiac surgery patients. We aimed to determine the association between IIT and mortality in a mixed population of critically ill patients.MethodsWe conducted a cohort study comparing three consecutive time periods before and after IIT protocol implementation in a Level 1 trauma center: period I (no protocol); period II, target glucose 80 to 130 mg/dL; and period III, target glucose 80 to 110 mg/dL. Subjects were 10,456 patients admitted to intensive care units (ICUs) between 1 March 2001 and 28 February 2005. The main study endpoints were ICU and hospital mortality, Sequential Organ Failure Assessment score, and occurrence of hypoglycemia. Multivariable regression analysis was used to evaluate mortality and organ dysfunction during periods II and III relative to period I.ResultsInsulin administration increased over time (9% period I, 25% period II, and 42% period III). Nonetheless, patients in period III had a tendency toward higher adjusted hospital mortality (odds ratio [OR] 1.15, 95% confidence interval [CI] 0.98, 1.35) than patients in period I. Excess hospital mortality in period III was present primarily in patients with an ICU length of stay of 3 days or less (OR 1.47, 95% CI 1.11, 1.93 There was an approximately fourfold increase in the incidence of hypoglycemia from periods I to III.ConclusionA policy of IIT in a group of ICUs from a single institution was not associated with a decrease in hospital mortality. These results, combined with the findings from several recent randomized trials, suggest that further study is needed prior to widespread implementation of IIT in critically ill patients.

Comparative Efficacy and Safety of 4 Randomized Regimens to Treat Early Pseudomonas aeruginosa Infection in Children With Cystic Fibrosis

OBJECTIVE To investigate the efficacy and safety of 4 antipseudomonal treatments in children with cystic fibrosis with recently acquired Pseudomonas aeruginosa infection. DESIGN Randomized controlled trial. SETTING Multicenter trial in the United States. PARTICIPANTS Three hundred four children with cystic fibrosis aged 1 to 12 years within 6 months of P aeruginosa detection. INTERVENTIONS Participants were randomized to 1 of 4 antibiotic regimens for 18 months (six 12-week quarters) between December 2004 and June 2009. Participants randomized to cycled therapy received tobramycin inhalation solution (300 mg twice a day) for 28 days, with oral ciprofloxacin (15-20 mg/kg twice a day) or oral placebo for 14 days every quarter, while participants randomized to culture-based therapy received the same treatments only during quarters with positive P aeruginosa cultures. MAIN OUTCOME MEASURES The primary end points were time to pulmonary exacerbation requiring intravenous antibiotics and proportion of P aeruginosa -positive cultures. RESULTS The intention-to-treat analysis included 304 participants. There was no interaction between treatments. There were no statistically significant differences in exacerbation rates between cycled and culture-based groups (hazard ratio, 0.95; 95% confidence interval [CI], 0.54-1.66) or ciprofloxacin and placebo (hazard ratio, 1.45; 95% CI, 0.82-2.54). The odds ratios of P aeruginosa- positive culture comparing the cycled vs culture-based group were 0.78 (95% CI, 0.49-1.23) and 1.10 (95% CI, 0.71-1.71) comparing ciprofloxacin vs placebo. Adverse events were similar across groups. CONCLUSIONS No difference in the rate of exacerbation or prevalence of P aeruginosa positivity was detected between cycled and culture-based therapies. Adding ciprofloxacin produced no benefits. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT00097773.

Effect of acute lung injury and acute respiratory distress syndrome on outcome in critically ill trauma patients

ObjectiveAcute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are known to be associated with increased mortality and costs in trauma patients. We estimated the independent impact of these conditions on mortality and cost, beyond the severity of injury with which they are correlated. DesignOne-year prospective cohort. Patients and SettingAll trauma patients admitted to the intensive care unit in a level I center were evaluated daily for ALI/ARDS using the American-European Consensus Conference definition. Measurements and Main ResultsThe main outcome measures were hospital mortality and costs. Logistic regression was used to model hospital mortality in relation to the presence of ALI and ARDS, adjusting for trauma severity (Injury Severity Score), Acute Physiology Score, and age. Hospital costs were modeled using multivariable linear regression. Of the 1,296 trauma patients surviving beyond the first day, 4% experienced ALI (defined as Pao2/Fio2 of 201–300 mm Hg) and 12% had ARDS (Pao2/Fio2 ≤ 200 mm Hg). The crude relative risk of mortality was 2.24 (95% confidence interval, 0.92–5.45) in patients with ALI and 3.84 (95% confidence interval, 2.41–6.13) in patients with ARDS compared with those without ALI/ARDS. However, there was no association of mortality with ALI (relative risk, 0.99; 95% confidence interval, 0.29–3.36) or with ARDS (relative risk, 1.23; 95% confidence interval, 0.63–2.43) after adjustment for age, Injury Severity Score, and Acute Physiology Score. Among patients of comparable age, severity score, and length of stay, median cost was 20% to 30% higher for those with ALI/ARDS. ConclusionsThere is no additional mortality associated with ALI/ARDS above and beyond the factors that can be measured at intensive care unit admission. Therefore, mortality in trauma patients is explained by injury severity at admission and is not affected by the subsequent occurrence of ALI/ARDS. Nonetheless, ALI/ARDS was associated with increased intensive care unit stay and hospital cost, independent of trauma severity.

Management guided by brain tissue oxygen monitoring and outcome following severe traumatic brain injury.

OBJECT The authors sought to describe changes in clinical management associated with brain tissue oxygen (PbO(2)) monitoring and how these changes affected outcomes and resource utilization. METHODS The cohort study comprised 629 patients admitted to a Level I trauma center with a diagnosis of severe traumatic brain injury over a period of 3 years. Hospital mortality rate, neurological outcome, and resource utilization of 123 patients who underwent both PbO(2) and intracranial pressure (ICP) monitoring were compared with the same measures in 506 patients who underwent ICP monitoring only. The main outcomes were hospital mortality rate, functional independence at hospital discharge, duration of mechanical ventilation, hospital length of stay, and hospital cost. Multivariable regression with robust variance was used to estimate the adjusted differences in the main outcome measures between patient groups. The models were adjusted for patient age, severity of injury, and pathological features seen on head CT scan at admission. RESULTS On average, patients who underwent ICP/PbO(2) monitoring were younger and had more severe injuries than patients who received ICP monitoring alone. Relatively more patients treated with PbO(2) monitoring received osmotic therapy, vasopressors, and prolonged sedation. After adjustment for baseline characteristics, the hospital mortality rate was, if anything, slightly higher in patients undergoing PbO(2)-guided management than in patients monitored with ICP only (adjusted mortality difference 4.4%, 95% CI -3.9 to 13%). Patients who underwent PbO(2)-guided management also had lower adjusted functional independence scores at hospital discharge (adjusted score difference -0.75, 95% CI -1.41 to -0.09). There was a 27% relative increase (95% CI 6-53%) in the median hospital length of stay when the PbO(2) group was compared with the ICP-only group. CONCLUSIONS The mortality rate in patients with traumatic brain injury whose clinical management was guided by PbO(2) monitoring was not reduced in comparison with that in patients who received ICP monitoring alone. Brain tissue oxygen monitoring was associated with worse neurological outcome and increased hospital resource utilization.

Early anti-pseudomonal acquisition in young patients with cystic fibrosis: Rationale and design of the EPIC clinical trial and observational study , ☆ , ☆☆

BACKGROUND The primary cause of morbidity and mortality in patients with cystic fibrosis (CF) is progressive obstructive pulmonary disease due to chronic endobronchial infection, particularly with Pseudomonas aeruginosa (Pa). Risk factors for and clinical impact of early Pa infection in young CF patients are less well understood. PURPOSE The present studies are designed to evaluate risk factors and outcomes associated with early Pa acquisition, and the benefits and harms of four anti-pseudomonal treatment regimens in young CF patients initiated after the first Pa positive respiratory culture. METHODS The Early Pseudomonas Infection Control (EPIC) program consists of two studies, a randomized multicenter trial in CF patients ages 1-12 years at first isolation of Pa from a respiratory culture, and a longitudinal cohort study enrolling Pa-negative patients. Using a factorial design, trial participants are assigned for 18 months to either anti-pseudomonal treatment on a scheduled quarterly basis (cycled therapy) or based on recovery of Pa from quarterly respiratory cultures (culture-based therapy). The study drugs include inhaled tobramycin (300 mg BID) for 28 days, combined with either oral ciprofloxacin (15-20 mg/kg BID) or oral placebo for 14 days. The primary endpoints of the trial are the time to pulmonary exacerbation requiring IV antibiotics or hospitalization for respiratory symptoms, and the proportion of patients with new Pa-positive respiratory cultures during the study. The broad goals of the observational study are to describe the risk factors and outcomes associated with early acquisition of Pa. 306 patients were randomized in the clinical trial and 1787 were enrolled in the cohort study. CONCLUSIONS These companion studies will provide valuable epidemiological and microbiological information on early CF lung disease and Pa acquisition, and safety and clinical efficacy data on anti-pseudomonal treatment strategies for early Pa infections in the airways of young children with CF.

Fluid responsiveness in spontaneously breathing patients : A review of indexes used in intensive care

LEARNING OBJECTIVESOn completion of this article, the reader should be able to: Define static and dynamic indexes. List indexes that are valuable to predict fluid responsiveness in spontaneously breathing patients. Use this information in a clinical setting. All authors have disclosed that they have no financial relationships or interests in any commercial companies pertaining to this educational activity. Wolters Kluwer Health has identified and resolved all faculty conflicts of interest regarding this educational activity. Visit the Critical Care Medicine Web site (www.ccmjournal.org) for information on obtaining continuing medical education credit. Objective:In spontaneously breathing patients, indexes predicting hemodynamic response to volume expansion are very much needed. The present review discusses the clinical utility and accuracy of indexes tested as bedside indicators of preload reserve and fluid responsiveness in hypotensive, spontaneously breathing patients. Data Source:We conducted a literature search of the MEDLINE database and the trial register of the Cochrane Group. Study Selection:Identification of reports investigating, prospectively, indexes of fluid responsiveness in spontaneously breathing critically ill patients. All the studies defined the response to fluid therapy after measuring cardiac output and stroke volume using the thermodilution technique. We did not score the methodological quality of the included studies before the data analysis. Data Extraction:A total of eight prospective clinical studies in critically ill patients were included. Only one publication evaluated cardiac output changes induced by fluid replacement in a selected population of spontaneously breathing critically ill patients. Data Synthesis:Based on this review, we can only conclude that static indexes are valuable tools to confirm that the fluid volume infused reaches the cardiac chambers, and therefore these indexes inform about changes in cardiac preload. However, respiratory variation in right atrial pressure, which represents a dynamic measurement, seems to identify hypotension related to a decrease in preload and to distinguish between responders and nonresponders to a fluid challenge. Conclusions:Further studies should address the question of the role of static indexes in predicting cardiac output improvement following fluid infusion in spontaneously breathing patients.

Initial Pseudomonas aeruginosa treatment failure is associated with exacerbations in cystic fibrosis

The risk of pulmonary exacerbation following Pseudomonas aeruginosa (Pa) acquisition in children with cystic fibrosis (CF) is unknown.

Characterization of cardiac dysfunction in sepsis: an ongoing challenge.

ABSTRACT Sepsis-induced cardiomyopathy (SIC), which is a common morbid condition, occurs in patients with severe sepsis and septic shock. The clinical characterization of SIC has been largely concept-driven. Heart function has traditionally been evaluated according to two basic conceptual models: a hydraulic pump system, whereby the output from the heart is entirely dependent on its input, or a hemodynamic pump, whereby the cardiac output is a function of preload, global ventricular performance, and afterload. Minimal attention has been given to the intrinsic contractile function of the heart or to the interaction between the peripheral circulation and the intrinsic myocardial function in sepsis. Currently, SIC is assumed to be the result of the interaction of microorganisms that activate the physiopathological pathways and cellular signaling mechanisms that lead to intrinsic myocardial dysfunction. However, the animal models used to study SIC exhibit multiple limitations. This review addresses the conceptual background, historical perspectives, physiologic mechanisms, current evidence, and limitations of SIC characterization. It also highlights potential future directions for the hemodynamic assessment of the intrinsic contractile function of the heart to overcome current methodological limitations. Finally, the present review recommends the exploration of additional potential mechanisms underlying SIC.

Hemodynamic management of subarachnoid hemorrhage.

Hemodynamic augmentation therapy is considered standard treatment to help prevent and treat vasospasm and delayed cerebral ischemia. Standard triple-H therapy combines volume expansion (hypervolemia), blood pressure augmentation (hypertension), and hemodilution. An electronic literature search was conducted of English-language papers published between 2000 and October 2010 that focused on hemodynamic augmentation therapies in patients with subarachnoid hemorrhage. Among the eligible reports identified, 11 addressed volume expansion, 10 blood pressure management, 4 inotropic therapy, and 12 hemodynamic augmentation in patients with unsecured aneurysms. While hypovolemia should be avoided, hypervolemia did not appear to confer additional benefits over normovolemic therapy, with an excess of side effects occurring in patients treated with hypervolemic targets. Overall, hypertension was associated with higher cerebral blood flow, regardless of volume status (normo- or hypervolemia), with neurological symptom reversal seen in two-thirds of treated patients. Limited data were available for evaluating inotropic agents or hemodynamic augmentation in patients with additional unsecured aneurysms. In the context of sparse data, no incremental risk of aneurysmal rupture has been reported with the induction of hemodynamic augmentation.