Heart rate variability and subsequent psychological distress among family members of intensive care unit patients.

OBJECTIVE: To determine whether heart rate variability (HRV; a physiological measure of acute stress) is associated with persistent psychological distress among family members of adult intensive care unit (ICU) patients. METHODS: This prospective study investigated family members of patients admitted to a study ICU. Participants' variability in heart rate tracings were measured by low frequency (LF)/high frequency (HF) ratio and detrended fluctuation analysis (DFA). Questionnaires were completed 3 months after enrollment to ascertain outcome rates of anxiety, depression, and post-traumatic stress disorder (PTSD). RESULTS: Ninety-nine participants were enrolled (median LF/HF ratio, 0.92 [interquartile range, 0.64-1.38]). Of 92 participants who completed the 3-month follow-up, 29 (32%) had persistent anxiety. Logistic regression showed that LF/HF ratio (odds ratio [OR] 0.85, 95% confidence interval [CI] 0.43, 1.53) was not associated with 3-month outcomes. In an exploratory analysis, DFA α (OR 0.93, 95% CI 0.87, 0.99), α1 (OR 0.97, 95% CI 0.94, 0.99), and α2 (OR 0.94, 95% CI 0.88, 0.99) scaling components were associated with PTSD development. CONCLUSION: Almost one-third of family members experienced anxiety at three months after enrollment. HRV, measured by LF/HF ratio, was not a predictor of psychologic distress, however, exploratory analyses indicated that DFA may be associated with PTSD outcomes.

Depression and Change in Caregiver Burden Among Family Members of Intensive Care Unit Survivors.

BACKGROUND: Family members of patients in intensive care units may experience psychological distress and substantial caregiver burden. OBJECTIVE: To evaluate whether change in caregiver burden from intensive care unit admission to 3-month follow-up is associated with caregiver depression at 3 months. METHODS: Caregiver burden was assessed at enrollment and 3 months later, and caregiver depression was assessed at 3 months. Depression was measured with the Hospital Anxiety and Depression Score. The primary analysis was the association between depression at 3 months and change in caregiver burden, controlling for a history of caregiver depression. RESULTS: One hundred one participants were enrolled; 65 participants had a surviving loved one and completed 3-month follow-up. At 3-month follow-up, 12% of participants met criteria for depression. Increased caregiver burden over time was significantly associated with depression at follow-up (Fisher exact test, P = .004), although this association was not significant after controlling for self-reported history of depression at baseline (Cochran-Mantel-Haenszel test, P = .23). CONCLUSIONS: Family members are increasingly recognized as a vulnerable population susceptible to negative psychological outcomes after a loved one's admission to the intensive care unit. In this small sample, no significant association was found between change in caregiver burden and depression at 3 months after controlling for baseline depression.

Persistence of patient and family experiences of critical illness.

OBJECTIVE: To investigate: (1) patient and family experiences with healthcare and the intensive care unit (ICU); (2) experiences during their critical illness; (3) communication and decision making during critical illness; (4) feelings about the ICU experience; (5) impact of the critical illness on their lives; and (6) concerns about their future after the ICU. DESIGN: Four semistructured focus group interviews with former ICU patients and family members. SETTINGS: Multicultural community group and local hospitals containing medical/surgical ICUs. PARTICIPANTS: Patients and family who experienced a critical illness within the previous 10 years. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Four separate focus groups each lasting a maximum of 150 min and consisting of a total of 21 participants were held. Focus groups were conducted using a semistructured script including six topics relating to the experience of critical illness that facilitated deduction and the sorting of data by thematic analysis into five predominant themes. The five main themes that emerged from the data were: (1) personalised stories of the critical illness; (2) communication and shared decision making, (3) adjustment to life after critical illness, (4) trust towards clinical team and relevance of cultural beliefs and (5) end-of-life decision making. Across themes, we observed a misalignment between the medical system and patient and family values and priorities. CONCLUSIONS: The experience of critical illness of a diverse group of patients and families can remain vivid for years after ICU discharge. The identified themes reflect the strength of memory of such pivotal experiences and the importance of a narrative around those experiences. Clinicians need to be aware of the lasting effects of critical illness has on patients and families.

Percentage of Time in Range 70 to 139 mg/dL Is Associated With Reduced Mortality Among Critically Ill Patients Receiving IV Insulin Infusion.

BACKGROUND: In addition to hyperglycemia, hypoglycemia, and glycemic variability, reduced time in targeted blood glucose range (TIR) is associated with increased risk of death in critically ill patients. This relation between TIR and mortality may be confounded by diabetic status and antecedent glycemic control. METHODS: This study retrospectively analyzed critically ill patients managed with the same IV insulin protocol at multiple centers. The percentage of TIR between 70 and 139 mg/dL was calculated. Patients with diabetic ketoacidosis, patients who had < 10 blood glucose readings, and patients with repeat admissions were excluded. The highest recorded glycosylated hemoglobin value in the preceding 3 months or up to 1 month following admission were used as a surrogate for the patient's preexisting glucose control. Stratified regression analyses were performed for 30-day mortality, with covariates of age, sex, TIR ≥ 80%, Acute Physiology Score, and Charlson Comorbidity Index. RESULTS: A total of 9,028 patients, 53.2% of whom had diabetes, were studied. Median TIR was 84.1% for nondiabetic patients and 64.5% for patients with diabetes. Mortality was lower in those with TIR > 80% compared with those with TIR ≤ 80% (12.4% vs 19.2%; P < .001). TIR > 80% was independently associated with reduced mortality in nondiabetic patients (OR, 0.52; P < .001), patients with diabetes (OR, 0.69; P = .001), and patients with well-controlled disease (OR, 0.50; P < .001) but not in patients with poorly controlled disease (OR, 0.86; P = .40). CONCLUSIONS: TIR was independently associated with mortality in critically ill patients, particularly those with good antecedent glucose control.

Lower Glucose Target Is Associated With Improved 30-Day Mortality in Cardiac and Cardiothoracic Patients.

BACKGROUND: Practice guidelines recommend against intensive insulin therapy in patients who are critically ill based on trials that had high rates of severe hypoglycemia. Intermountain Healthcare uses a computerized IV insulin protocol that allows choice of blood glucose (BG) targets (80-110 vs 90-140 mg/dL) and has low rates of severe hypoglycemia. We sought to study the effects of BG target on mortality in adult patients in cardiac ICUs that have very low rates of severe hypoglycemia. METHODS: Critically ill patients receiving IV insulin were treated with either of two BG targets (80-110 vs 90-140 mg/dL). We created a propensity score for BG target using factors thought to have influenced clinicians' choice, and then we performed a propensity score-adjusted regression analysis for 30-day mortality. RESULTS: There were 1,809 patients who met inclusion criteria. Baseline patient characteristics were similar. Median glucose was lower in the 80-110 mg/dL group (104 vs 122 mg/dL, P < .001). Severe hypoglycemia occurred at very low rates in both groups (1.16% vs 0.35%, P = .051). Unadjusted 30-day mortality was lower in the 80-110 mg/dL group (4.3% vs 9.2%, P < .001). This remained after propensity score-adjusted regression (OR, 0.65; 95% CI, 0.43-0.98; P = .04). CONCLUSIONS: Tight glucose control can be achieved with low rates of severe hypoglycemia and is associated with decreased 30-day mortality in a cohort of largely patients in cardiac ICUs. Although such findings should not be used to guide clinical practice at present, the use of tight glucose control should be reexamined using a protocol that has low rates of severe hypoglycemia.

Preliminary Identification of Coping Profiles Relevant to Surrogate Decision Making in the ICU.

OBJECTIVE: The Intensive Care Unit (ICU) is a stressful environment for families of critically ill patients and these individuals are at risk to develop persistent psychological morbidity. Our study objective was to identify individual differences in coping with stress and information presentation preferences of respondents exposed to a simulated ICU experience. METHODS: Participants were recruited from a university and two community populations. Participants completed questionnaires that measured demographic information and characteristics that may be relevant to an individual's ICU experience. Quality of life was measured by the EQ-5D, personality dimensions were examined with the abbreviated Big Five inventory, coping with stress was assessed with Brief COPE. Shared decision making preferences were assessed by the Degner Control Preferences Scale (CPS) and information seeking style was assessed with the Miller Behavioral Style Scale (MBSS). Social support was examined using an abbreviated version of the Social Relationship Index. Participants also completed a vignette-based simulated ICU experience, in which they made a surrogate decision on behalf of a loved one in the ICU. RESULTS: Three hundred forty-three participants completed the study. Three distinct coping profiles were identified: adaptive copers, maladaptive copers, and disengaged copers. Profiles differed primarily on coping styles, personality, quality of their closest social relationship, and history of anxiety and depression. Responses to the simulated ICU decision making experience differed across profiles. Disengaged copers (15%) were more likely to elect to refuse dialysis on behalf of an adult sibling compared to adaptive copers (7%) or maladaptive copers (5%) (p = 0.03). Notably, the MBSS and the CPS did not differ by coping profile. CONCLUSION: Distinct coping profiles are associated with differences in responses to a simulated ICU experience. Tailoring communication and support to specific coping profiles may represent an important pathway to improving ICU experience for patients and families.

Coefficient of glucose variation is independently associated with mortality in critically ill patients receiving intravenous insulin.

INTRODUCTION: Both patient- and context-specific factors may explain the conflicting evidence regarding glucose control in critically ill patients. Blood glucose variability appears to correlate with mortality, but this variability may be an indicator of disease severity, rather than an independent predictor of mortality. We assessed blood glucose coefficient of variation as an independent predictor of mortality in the critically ill. METHODS: We used eProtocol-Insulin, an electronic protocol for managing intravenous insulin with explicit rules, high clinician compliance, and reproducibility. We studied critically ill patients from eight hospitals, excluding patients with diabetic ketoacidosis and patients supported with eProtocol-insulin for < 24 hours or with < 10 glucose measurements. Our primary clinical outcome was 30-day all-cause mortality. We performed multivariable logistic regression, with covariates of age, gender, glucose coefficient of variation (standard deviation/mean), Charlson comorbidity score, acute physiology score, presence of diabetes, and occurrence of hypoglycemia < 60 mg/dL. RESULTS: We studied 6101 critically ill adults. Coefficient of variation was independently associated with 30-day mortality (odds ratio 1.23 for every 10% increase, P < 0.001), even after adjustment for hypoglycemia, age, disease severity, and comorbidities. The association was higher in non-diabetics (OR = 1.37, P < 0.001) than in diabetics (OR 1.15, P = 0.001). CONCLUSIONS: Blood glucose variability is associated with mortality and is independent of hypoglycemia, disease severity, and comorbidities. Future studies should evaluate blood glucose variability.

The evolution of eProtocols that enable reproducible clinical research and care methods.

Unnecessary variation in clinical care and clinical research reduces our ability to determine what healthcare interventions are effective. Reducing this unnecessary variation could lead to further healthcare quality improvement and more effective clinical research. We have developed and used electronic decision support tools (eProtocols) to reduce unnecessary variation. Our eProtocols have progressed from a locally developed mainframe computer application in one clinical site (LDS Hospital) to web-based applications available in multiple languages and used internationally. We use eProtocol-insulin as an example to illustrate this evolution. We initially developed eProtocol-insulin as a local quality improvement effort to manage stress hyperglycemia in the adult intensive care unit (ICU). We extended eProtocol-insulin use to translate our quality improvement results into usual clinical care at Intermountain Healthcare ICUs. We exported eProtocol-insulin to support research in other US and international institutions, and extended our work to the pediatric ICU. We iteratively refined eProtocol-insulin throughout these transitions, and incorporated new knowledge about managing stress hyperglycemia in the ICU. Based on our experience in the development and clinical use of eProtocols, we outline remaining challenges to eProtocol development, widespread distribution and use, and suggest a process for eProtocol development. Technical and regulatory issues, as well as standardization of protocol development, validation and maintenance, need to be addressed. Resolution of these issues should facilitate general use of eProtocols to improve patient care.

A modified sequential organ failure assessment score for critical care triage.

OBJECTIVE: The Sequential Organ Failure Assessment (SOFA) score has been recommended for triage during a mass influx of critically ill patients, but it requires laboratory measurement of 4 parameters, which may be impractical with constrained resources. We hypothesized that a modified SOFA (MSOFA) score that requires only 1 laboratory measurement would predict patient outcome as effectively as the SOFA score. METHODS: After a retrospective derivation in a prospective observational study in a 24-bed medical, surgical, and trauma intensive care unit, we determined serial SOFA and MSOFA scores on all patients admitted during the 2008 calendar year and compared the ability to predict mortality and the need for mechanical ventilation. RESULTS: A total of 1770 patients (56% male patients) with a 30-day mortality of 10.5% were included in the study. Day 1 SOFA and MSOFA scores performed equally well at predicting mortality with an area under the receiver operating curve (AUC) of 0.83 (95% confidence interval 0.81-.85) and 0.84 (95% confidence interval 0.82-.85), respectively (P = .33 for comparison). Day 3 SOFA and MSOFA predicted mortality for the 828 patients remaining in the intensive care unit with an AUC of 0.78 and 0.79, respectively. Day 5 scores performed less well at predicting mortality. Day 1 SOFA and MSOFA predicted the need for mechanical ventilation on day 3, with an AUC of 0.83 and 0.82, respectively. Mortality for the highest category of SOFA and MSOFA score (>11 points) was 53% and 58%, respectively. CONCLUSIONS: The MSOFA predicts mortality as well as the SOFA and is easier to implement in resource-constrained settings, but using either score as a triage tool would exclude many patients who would otherwise survive.

Blood glucose dysregulation and cognitive outcome in ARDS survivors.

OBJECTIVE: Hyperglycaemia is common in critically ill patients and may contribute to increased mortality and morbidity. This study assessed the impact of blood glucose on cognitive outcome in acute respiratory distress syndrome (ARDS) patients' 1 year post-hospital discharge. DESIGN: Retrospective data for 74 ARDS survivors who were enrolled in a prospective mechanical ventilation randomized clinical trial. A standard protocol was used to manage blood glucose. The highest, lowest, mean and standard deviation glucose values were examined, as well as duration of hypoxemia and other clinical data. Standardized neuropsychological tests were administered to identify cognitive sequelae. Logistic regression models were used to assess risk factors for cognitive sequelae. MEASUREMENTS AND RESULTS: There was a significant relationship between the blood glucose and cognitive sequelae. Greater duration of mechanical ventilation and highest blood glucose predicted cognitive sequelae. CONCLUSIONS: Blood glucose dysregulation, specifically moderate hyperglycaemia and ICU length of stay, predicted adverse cognitive sequelae in ARDS patients.

Risk factors for depression and anxiety in survivors of acute respiratory distress syndrome.

OBJECTIVE: Depression and anxiety are common morbidities of critical illness. We assessed risk factors of depression and anxiety in Acute Respiratory Distress Syndrome (ARDS) survivors at 1 and 2 years post-hospital discharge. METHOD: Risk factors for depression and anxiety at 1 and 2 years were assessed using stepwise multiple regression analyses, with and without 1-year outcomes. RESULTS: ARDS survivors had depression (16% and 23%) and anxiety (24% and 23%) at 1 and 2 years, respectively. Predictors of depression at 1 year were alcohol dependence, female gender and younger age (P=.006). Predictors of anxiety were ratio of arterial oxygen tension to inspired oxygen fraction and duration of mechanical ventilation (P<.005). Predictors of depression at 2 years were depression at 1 year and the presence of cognitive sequelae (P<.0001). Predictors of anxiety at 2 years was anxiety at 1 year (P<.0001). CONCLUSIONS: Medical variables that predicted depression or anxiety at 1 year no longer predicted depression and anxiety at 2 years. Medical variables appear to have a short-term effect on psychiatric outcomes. At 2 years lifestyle behaviors including history of smoking along with cognitive sequelae, depression and anxiety at 1 year predict depression and anxiety.

Association of physical examination with pulmonary artery catheter parameters in acute lung injury.

OBJECTIVE: To correlate physical examination findings, central venous pressure, fluid output, and central venous oxygen saturation with pulmonary artery catheter parameters. DESIGN: Retrospective study. SETTING: Data from the multicenter Fluid and Catheter Treatment Trial of the National Institutes of Health Acute Respiratory Distress Syndrome Network. PATIENTS: Five hundred thirteen patients with acute lung injury randomized to treatment with a pulmonary artery catheter. INTERVENTIONS: Correlation of physical examination findings (capillary refill time >2 secs, knee mottling, or cool extremities), central venous pressure, fluid output, and central venous oxygen saturation with parameters from a pulmonary artery catheter. MEASUREMENTS: We determined association of baseline physical examination findings and on-study parameters of central venous pressure and central venous oxygen saturation with cardiac index <2.5 L/min/m2 and mixed venous oxygen saturation <60%. We determined correlation of baseline central venous oxygen saturation and mixed venous oxygen saturation and predictive value of a low central venous oxygen saturation for a low mixed venous oxygen saturation. MEASUREMENTS AND MAIN RESULTS: Prevalence of cardiac index <2.5 and mixed venous oxygen saturation <60% was 8.1% and 15.5%, respectively. Baseline presence of all three physical examination findings had low sensitivity (12% and 8%), high specificity (98% and 99%), low positive predictive value (40% and 56%), but high negative predictive value (93% and 86%) for cardiac index <2.5 and mixed venous oxygen saturation <60%, respectively. Central venous oxygen saturation <70% predicted a mixed venous oxygen saturation <60% with a sensitivity 84%,specificity 70%, positive predictive value 31%, and negative predictive value of 96%. Low cardiac index correlated with cool extremities, high central venous pressure, and low 24-hr fluid output; and low mixed venous oxygen saturation correlated with knee mottling and high central venous pressure, but these correlations were not found to be clinically useful. CONCLUSIONS: In this subset of patients with acute lung injury, there is a high prior probability that cardiac index and mixed venous oxygen saturation are normal and physical examination findings of ineffective circulation are not useful for predicting low cardiac index or mixed venous oxygen saturation. Central venous oxygen saturation <70% does not accurately predict mixed venous oxygen saturation <60%, but a central venous oxygen saturation >or=70% may be useful to exclude mixed venous oxygen saturation <60%.

Multicenter validation of a computer-based clinical decision support tool for glucose control in adult and pediatric intensive care units.

INTRODUCTION: Hyperglycemia during critical illness is common, and intravenous insulin therapy (IIT) to normalize blood glucose improves outcomes in selected populations. Methods differ widely in complexity, insulin dosing approaches, efficacy, and rates of hypoglycemia. We developed a simple bedside-computerized decision support protocol (eProtocol-insulin) that yields promising results in the development center. We examined the effectiveness and safety of this tool in six adult and five pediatric intensive care units (ICUs) in other centers. METHODS: We required attending physicians of eligible patients to independently intend to use intravenous insulin to normalize blood glucose. We used eProtocol-insulin for glucose control for a duration determined by the clinical caregivers. Adults had an anticipated length of stay of 3 or more days. In pediatric ICUs, we also required support or intended support with mechanical ventilation for greater than 24 hours or with a vasoactive infusion. We recorded all instances in which eProtocol-insulin instructions were not accepted and all blood glucose values. An independent data safety and monitoring board monitored study results and subject safety. Bedside nurses were selected randomly to complete a paper survey describing their perceptions of quality of care and workload related to eProtocol-insulin use. RESULTS: Clinicians accepted 93% of eProtocol-insulin instructions (11,773/12,645) in 100 adult and 48 pediatric subjects. Forty-eight percent of glucose values were in the target range. Both of these results met a priori-defined efficacy thresholds. Only 0.18% of glucose values were < or =40 mg/dl. This is lower than values reported in prior IIT studies. Although nurses reported eProtocol-insulin required as much work as managing a mechanical ventilator, most nurses felt eProtocol-insulin had a low impact on their ability to complete non-IIT nursing activities. CONCLUSIONS: A multicenter validation demonstrated that eProtocol-insulin is a valid, exportable tool that can assist clinicians in achieving control of glucose in critically ill adults and children.

Assessing data quality in manual entry of ventilator settings.

OBJECTIVE: To evaluate the data quality of ventilator settings recorded by respiratory therapists using a computer charting application and assess the impact of incorrect data on computerized ventilator management protocols. DESIGN An analysis of 29,054 charting events gathered over 12 months from 678 ventilated patients (1,736 ventilator days) in four intensive care units at a tertiary care hospital. MEASUREMENTS: Ten ventilator settings were examined, including fraction of inspired oxygen (Fio (2)), positive end-expiratory pressure (PEEP), tidal volume, respiratory rate, peak inspiratory flow, and pressure support. Respiratory therapists entered values for each setting approximately every two hours using a computer charting application. Manually entered values were compared with data acquired automatically from ventilators using an implementation of the ISO/IEEE 11073 Medical Information Bus (MIB). Data quality was assessed by measuring the percentage of time that the two sources matched. Charting delay, defined as the interval between data observation and data entry, also was measured. RESULTS: The percentage of time that settings matched ranged from 99.0% (PEEP) to 75.9% (low tidal volume alarm setting). The average charting delay for each charting event was 6.1 minutes, including an average of 1.8 minutes spent entering data in the charting application. In 559 (3.9%) of 14,263 suggestions generated by computerized ventilator management protocols, one or more manually charted setting values did not match the MIB data. CONCLUSION: Even at institutions where manual charting of ventilator settings is performed well, automatic data collection can eliminate delays, improve charting efficiency, and reduce errors caused by incorrect data.

Two-year cognitive, emotional, and quality-of-life outcomes in acute respiratory distress syndrome.

Acute respiratory distress syndrome (ARDS) has a high mortality and is associated with significant morbidity. Prior outcome studies have focused predominant on short-term outcomes (6-12 months). We assessed longitudinal neurocognitive, emotional, and quality of life in ARDS survivors at hospital discharge, and 1 and 2 years after hospital discharge using neuropsychologic tests and emotional and quality-of-life questionnaires. Neurocognitive sequelae occurred in 73% (54 of 74) of ARDS survivors at hospital discharge, 46% (30 of 66) at 1 year, and 47% (29 of 62) at 2 years. ARDS survivors report moderate to severe depression (16% and 23%) and anxiety (24% and 23%) at 1 and 2 years, respectively. The ARDS survivors had decreased quality of life, with the physical domains improving at 1 year, with no additional change at 2 years. Role emotional, pain, and general health did not change from hospital discharge to 2 years. Mental health improved during the first year and declined at 2 years. ARDS results in significant neurocognitive and emotional morbidity and decreased quality of life that persists at least 2 years after hospital discharge. ARDS can cause significant long-term, brain-related morbidity manifest by neurocognitive impairments and decreased quality of life.

Quality of life, emotional, and cognitive function following acute respiratory distress syndrome.

Acute Respiratory Distress Syndrome (ARDS) is characterized by lung injury and hypoxemia, has a high mortality rate, and is associated with significant morbidity including cognitive and emotional sequelae and decreased quality of life. There is limited information regarding which of these factors are associated with decreased quality of life. This study assessed the relationships between quality of life, cognitive and emotional function in ARDS survivors at 1-year post-hospital discharge. Sixty-six ARDS survivors were administered a battery of neuropsychological tests, measures of emotional function and quality of life 1 year post-hospital discharge. At 1 year 45% of the ARDS patients had cognitive sequelae and 29% had mild to moderate symptoms of depression and anxiety. Depression, anxiety, and intensive care unit length of stay were significantly correlated with decreased quality of life. Cognitive impairments did not correlate with decreased quality of life. Illness severity and emotional function, but not cognitive sequelae, are associated with decreased quality of life 1 year following ARDS. ARDS is common and may result in significant cognitive and emotional morbidity and decreased quality of life.

The changing face of organ failure in ARDS.

OBJECTIVE: To study morbidity and mortality in ARDS patients from 1987 to 1999. DESIGN: Review of a prospectively collected database of ARDS patients. SETTING: Large, community hospital located in Salt Lake City, UT. PATIENTS: ARDS patients identified for the years 1987 to 1999. We prospectively identified ARDS patients at LDS Hospital in Salt Lake City, UT, using PaO(2)/fraction of inspired oxygen ratio (P/F) criteria, the presence of bilateral chest radiograph infiltrates, and the absence of left atrial hypertension. MEASUREMENTS: We assigned a primary risk factor for ARDS and identified the presence of organ failure before and after ARDS. We compared two temporal groups (ie, 1987 to 1990 vs 1994 to 1999) and used two criteria of arterial hypoxemia (P/F: patients from 1994 to 1999, < or = 105 and < or = 173; patients from 1987 to 1990, < or = 0.2) At 1,500 m (the altitude of Salt Lake City), a PaO(2) of < or = 173 corresponds to an alveolar-arterial oxygen pressure difference of < or = 200 at sea level. We used death at hospital discharge as an end point. MAIN RESULTS: We identified 516 ARDS patients with a P/F of < or = 105 (1987 to 1990, 256 patients; 1994 to 1999, 260 patients). Patients who had ARDS between 1994 and 1999 with a P/F of < or = 105 had a lower mortality rate than patients between 1987 and 1990 with a P/F of < or = 105 (44% vs 54%, respectively; p <.05). There were 288 patients with a P/F range of 106 to 173 during 1994 to 1999. Patients from 1994 to 1999 with a P/F of < or = 173 had a lower mortality rate compared to patients from 1987 to 1990 (35% vs 54%, respectively; p <.01). Patients from 1994 to 1999 (for both P/F groups) had statistically fewer total nonpulmonary organ failures (ie, more patients had zero organ failures or single organ failures) and fewer specific organ failures (ie, sepsis, cardiovascular failures, and CNS failures). There were statistically fewer cases of cardiovascular failure, sepsis, and in both periods (ie, prior to ARDS and after the onset of ARDS) for 1994-to-1999 patients with a P/F of < or = 105 compared to 1987-to-1990 patients with a P/F of < or = 105. CONCLUSIONS: Mortality from ARDS has decreased and is associated with decreased organ failure prior to and during the course of ARDS.

Platelet-activating factor acetylhydrolase is increased in lung lavage fluid from patients with acute respiratory distress syndrome.

OBJECTIVE: Platelet-activating factor (PAF) is a proinflammatory phospholipid that may contribute to inflammation in the acute respiratory distress syndrome (ARDS). PAF acetylhydrolase (PAF-AH) degrades PAF and regulates its biological activity. We characterized PAF-AH in bronchoalveolar lavage fluid from ARDS patients (n = 33, 22 survivors), patients at risk for ARDS (n = 6), and healthy controls (n = 6). DESIGN: Bronchoalveolar lavage was performed during acute (<96 hrs from onset), plateau (6 to 12 days), and late (> or = 14 days) phases of ARDS. PATIENTS: Intubated patients with ARDS or a risk factor for ARDS. MEASUREMENTS AND MAIN RESULTS: In ARDS, total bronchoalveolar lavage PAF-AH activity was markedly increased in the acute phase (87 +/- 89 mU/mL, n = 33) and then decreased in the plateau (23 +/- 14 mU/mL, n = 10) and late phases (19 +/- 14 mU/mL, n = 7) (p = .003). Total bronchoalveolar lavage PAF-AH activity during the acute phase of ARDS was also increased as compared with patients at risk for ARDS (16 +/- 13 mU/mL, n = 6) and healthy controls (3 +/- 3 mU/mL, n = 6) (p < .001). In contrast, plasma PAF-AH activities were the same in controls (3215 +/- 858 mU/mL, n = 6), in patients at risk for ARDS (3606 +/- 1607 mU/mL, n = 6), and during the acute phase of ARDS (3098 +/- 2395 mU/mL, n = 33) (p = .18). PAF-AH mRNA was present in alveolar macrophages in the acute phase of ARDS (five of six) and in at-risk patients (two of three) but not in healthy controls. CONCLUSIONS: PAF-AH activity is increased in bronchoalveolar lavage fluid from patients with ARDS. Likely sources include leakage of plasma PAF-AH into alveoli or release of PAF-AH from injured cells; however, the presence of PAF-AH mRNA in alveolar macrophages suggests that PAF-AH may be actively synthesized in the lungs of patients with ARDS. PAF-AH activity in the lungs of ARDS patients may regulate inflammation caused by PAF and related oxidized phospholipids generated in the inflammatory response.

Hyperbaric oxygen for acute carbon monoxide poisoning.

BACKGROUND: Patients with acute carbon monoxide poisoning commonly have cognitive sequelae. We conducted a double-blind, randomized trial to evaluate the effect of hyperbaric-oxygen treatment on such cognitive sequelae. METHODS: We randomly assigned patients with symptomatic acute carbon monoxide poisoning in equal proportions to three chamber sessions within a 24-hour period, consisting of either three hyperbaric-oxygen treatments or one normobaric-oxygen treatment plus two sessions of exposure to normobaric room air. Oxygen treatments were administered from a high-flow reservoir through a face mask that prevented rebreathing or by endotracheal tube. Neuropsychological tests were administered immediately after chamber sessions 1 and 3, and 2 weeks, 6 weeks, 6 months, and 12 months after enrollment. The primary outcome was cognitive sequelae six weeks after carbon monoxide poisoning. RESULTS: The trial was stopped after the third of four scheduled interim analyses, at which point there were 76 patients in each group. Cognitive sequelae at six weeks were less frequent in the hyperbaric-oxygen group (19 of 76 [25.0 percent]) than in the normobaric-oxygen group (35 of 76 [46.1 percent], P=0.007), even after adjustment for cerebellar dysfunction and for stratification variables (adjusted odds ratio, 0.45 [95 percent confidence interval, 0.22 to 0.92]; P=0.03). The presence of cerebellar dysfunction before treatment was associated with the occurrence of cognitive sequelae (odds ratio, 5.71 [95 percent confidence interval, 1.69 to 19.31]; P=0.005) and was more frequent in the normobaric-oxygen group (15 percent vs. 4 percent, P=0.03). Cognitive sequelae were less frequent in the hyperbaric-oxygen group at 12 months, according to the intention-to-treat analysis (P=0.04). CONCLUSIONS: Three hyperbaric-oxygen treatments within a 24-hour period appeared to reduce the risk of cognitive sequelae 6 weeks and 12 months after acute carbon monoxide poisoning.