James F. Orme

Randomized, placebo-controlled trial of lisofylline for early treatment of acute lung injury and acute respiratory distress syndrome

Objective To determine whether the administration of lisofylline (1-[5R-hydroxyhexyl]-3,7-dimethylxanthine) would decrease mortality in patients with acute lung injury (ALI) or acute respiratory distress syndrome (ARDS). Design A prospective, randomized, double-blind, placebo-controlled, multicenter study. Setting Intensive care units at 21 hospitals at the ten centers constituting the ARDS Clinical Trials Network. Patients A total of 235 patients who met eligibility criteria were enrolled in the study (116 into the lisofylline group, 119 into the placebo group). Interventions Patients were randomized to receive either lisofylline or placebo. The dose of lisofylline was 3 mg/kg with a maximum dose of 300 mg intravenously every 6 hrs. The intravenous solution of study drug was administered over 10 mins every 6 hrs. Dosing was continued for 20 days or until the patient achieved 48 hrs of unassisted breathing. Measurements and Main Results The trial was stopped by the Data Safety Monitoring Board for futility at the first scheduled interim analysis. The patient groups had similar characteristics at enrollment. No significant safety concerns were associated with lisofylline therapy. There was no significant difference between groups in the number of patients who had died at 28 days (31.9% lisofylline vs. 24.7% placebo, p = .215). There was no significant difference between the lisofylline and placebo groups in terms of resolution of organ failures, ventilator-free days, infection-related deaths, or development of serious infection during the 28-day study period. The median number of organ failure–free days for the five nonpulmonary organ failures examined (cardiovascular, central nervous system, coagulation, hepatic, and renal) was not different between the lisofylline and placebo groups. Although lisofylline has been reported to decrease circulating free fatty acid levels, we did not find any such treatment effect compared with placebo. Conclusions In this study, there was no evidence that lisofylline had beneficial effects in the treatment of established ALI/ARDS.

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 risk of infection related to radial vs femoral sites for arterial catheterization.

To evaluate risk factors for infections associated with indwelling arterial catheters, 186 catheters were randomly allocated for either femoral or radial insertion in 155 critically ill patients. Femoral catheters were easier to insert and it was easier to obtain blood specimens from them. Rates of

A replicable method for blood glucose control in critically Ill patients.

Context:To ensure interpretability and replicability of clinical experiments, methods must be adequately explicit and should elicit the same decision from different clinicians who comply with the study protocol. Objective:The objective of this study was to determine whether clinician compliance with protocol recommendations exceeds 90%. Design:We developed an adequately explicit computerized protocol (eProtocol-insulin) for managing critically ill adult patient blood glucose. We monitored clinician compliance with eProtocol-insulin recommendations in four intensive care units in four hospitals and compared blood glucose distributions with those of a simple clinical guideline at one hospital and a paper-based protocol at another. All protocols and the guideline used intravenous insulin and 80 to 110 mg/dL (4.4–6.1 mmol/L) blood glucose targets. Setting:The setting for this study was four academic hospital intensive care units. Patients:This study included critically ill adults requiring intravenous insulin. Intervention:Intervention used in this study was a bedside computerized protocol for managing blood glucose. Main Outcome Measure:The main outcome measure was clinician compliance with eProtocol-insulin recommendations. Results:The number of patients was 31 to 458 and the number of blood glucose measurements was 2,226 to 19,925 among the four intensive care units. Clinician compliance with eProtocol-insulin recommendations was 91% to 98%. Blood glucose distributions were similar in the four hospitals (generalized linear model p = .18). Compared with the simple guideline, eProtocol-insulin glucose measurements within target increased from 21% to 39%, and mean blood glucose decreased from 142 to 115 mg/dL (generalized linear model p < .001). Compared with the paper-based protocol, eProtocol-insulin glucose measurements within target increased from 28% to 42%, and mean blood glucose decreased from 134 to 116 mg/dL (generalized linear model p = .001). Conclusions:The 91% to 98% clinician compliance indicates eProtocol-insulin is an exportable instrument that can establish a replicable experimental method for clinical trials of blood glucose management in critically ill adults. Control of blood glucose was better with eProtocol-insulin than with a simple clinical guideline or a paper-based protocol.

Calf-thigh sequential pneumatic compression compared with plantar venous pneumatic compression to prevent deep-vein thrombosis after non-lower extremity trauma.

OBJECTIVE To compare the effectiveness of calf-thigh sequential pneumatic compression devices with the effectiveness of plantar venous intermittent pneumatic compression devices in prevention of venous thrombosis after major trauma. SUBJECTS AND METHODS We evaluated 181 consecutive patients after major trauma without lower extremity injuries that precluded the use of pneumatic compression devices. We randomly assigned 149 patients to either calf-thigh sequential pneumatic compression or plantar venous pneumatic compression. After blinding the observers to the method of prophylaxis against deep-vein thrombosis, we performed bilateral compression ultrasonography on or before day 8 after randomization. RESULTS Among 149 randomized patients, 62 who received calf-thigh sequential pneumatic compression and 62 who received plantar venous intermittent pneumatic compression devices completed the trial. Thirteen patients randomized to plantar venous intermittent pneumatic compression (21.0%) and 4 patients randomized to calf-thigh sequential pneumatic compression (6.5%) had deep-vein thrombosis (p = 0.009). Seven of 13 patients with deep-vein thrombosis after prophylaxis with plantar venous intermittent pneumatic compression had bilateral deep-vein thromboses, whereas all 4 patients with deep-vein thrombosis after prophylaxis with calf-thigh sequential pneumatic compression had unilateral deep-vein thrombosis. CONCLUSION Calf-thigh sequential pneumatic compression prevents deep-vein thrombosis more effectively than plantar venous intermittent pneumatic compression after major trauma without lower extremity injuries.

Outcome of critically injured patients treated at Level I trauma centers versus full-service community hospitals.

Critically injured patients were identified by a CRAMS (circulation, respiration, abdomen, motor, speech) score of 6 or less while still in the field. They were prospectively followed as they received their care at the nearest medical facility according to the then-existing district Emergency Medical Services protocols. Those cared for by Level I trauma centers had a significantly reduced mortality rate compared to those treated at the other large full-service community hospitals. The commitment to Level I trauma care improves outcome of the critically injured, and field triage of the critically injured patient to these centers is indicated.

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.

Computer-based ICU data acquisition as an aid to clinical decision-making.

The critically ill patient places tremendous mental challenges and crucial time demands on intensive care nurses and physicians. Computers can ease these demands by automatically acquiring, storing, and displaying patient data. However, the computer can more effectively serve the staff if medical-decision protocols are implemented. This paper describes the use of a computer system designed to optimize medical care for the acutely ill patient.

Prospective evaluation of the CRAMS scale for triaging major trauma.

In order to effectively implement a community-wide trauma system, a mechanism of field triage is required. This process of triage should be simple to use and should accurately identify patients who are in need of level I trauma facility care. It should also allow the less critically injured to be cared for at the local hospital of their choice or at the nearest community hospital. The CRAMS (Circulation, Respiration, Abdomen, Motor, Speech) scale was prospectively studied as a potential triage tool by using it to score patients in the field and then comparing their scores to their emergency room dispositions and final outcomes. The CRAMS scale was easy to apply and accurately identified both the critically injured who should be triaged to a Level I center and the less critically injured who can be adequately cared for by Level II and III centers.

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%.