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Biomedical subjects

Roy G Brower

Publications and source records attributed to Roy G Brower.

At least 19 recordsLinked to original sources

Four methods of measuring tidal volume during high-frequency oscillatory ventilation.

OBJECTIVE: Assess the accuracy of four different methods of measuring tidal volume during simulated high-frequency oscillatory ventilation. DESIGN: In vitro study. SETTING: Research laboratory. SUBJECTS: Three differential pressure pneumotachometers, a modified Pitot tube, an ultrasound flowmeter, and an adult hot wire anemometer. INTERVENTIONS: Each device was placed in series with a Sensormedics 3100B high-frequency ventilator and an 8.0-mm endotracheal tube attached to a 48.9-L plethysmograph. Inspiratory/expiratory ratio was fixed at 1:1 and mean airway pressure at 10 cm H2O. Tidal volumes were calculated at each combination of frequency (f: 3, 4, 6, 8, 10, 12 Hz) and pressure amplitude (DeltaP: 30, 60, 90 cm H2O) by digital integration of the sampled flow signals from each device and compared with those calculated from pressure changes within the plethysmograph. The protocol was repeated after incorporation of frequency-specific calibrations to the flow-measuring algorithm of each device. The hot wire anemometer was further evaluated at Fio2 of 1.0, 37 degrees C, 80% humidity, mean airway pressure of 20 cm H2O, and an inspiratory/expiratory ratio of 1:2. MEASUREMENTS AND MAIN RESULTS: Tidal volumes were 36-305 mL. Bland-Altman analysis demonstrated that each device exhibited systematic bias before frequency-specific adjustment. After frequency-specific adjustment of the flow-measuring algorithm, the two most accurate and precise devices were the Hans Rudolph pneumotachometer, which exhibited a mean error of 0.2% (95% confidence interval, -3.0% to 3.4%), and the hot wire anemometer, which had a mean error of -1.1% (95% confidence interval, -5.5% to 3.3%). The hot wire anemometer remained accurate at Fio2 1.0, 37 degrees C, 80% humidity, mean airway pressure of 20 cm H2O, and an inspiratory/expiratory ratio of 1:2. CONCLUSIONS: Tidal volume can be measured during high-frequency oscillatory ventilation using a variety of techniques. Frequency-specific calibration improves the accuracy and precision of tidal volume measurements. Hot wire anemometry exhibits stable performance characteristics across the range of temperature, humidity, Fio2, and inspiratory/expiratory ratios encountered clinically, has a small deadspace, is unaffected by mean airway pressure, and is therefore suitable for clinical applications.

Adult↗

Tidal volume reduction in patients with acute lung injury when plateau pressures are not high.

Use of a volume- and pressure-limited mechanical ventilation strategy improves clinical outcomes of patients with acute lung injury and acute respiratory distress syndrome (ALI/ARDS). However, the extent to which tidal volumes and inspiratory airway pressures should be reduced to optimize clinical outcomes is a controversial topic. This article addresses the question, "Is there a safe upper limit to inspiratory plateau pressure in patients with ALI/ARDS?" We reviewed data from animal models with and without preexisting lung injury, studies of normal human respiratory system mechanics, and the results of five clinical trials of lung-protective mechanical ventilation strategies. We also present an original analysis of data from the largest of the five clinical trials. The available data from each of these assessments do not support the commonly held view that inspiratory plateau pressures of 30 to 35 cm H2O are safe. We could not identify a safe upper limit for plateau pressures in patients with ALI/ARDS.

Animals↗

Airway pressures, tidal volumes, and mortality in patients with acute respiratory distress syndrome.

OBJECTIVE: To determine the usual practice for setting tidal volume and other ventilatory parameters in patients with acute respiratory distress syndrome (ARDS) in the late 1990s and to determine the independent effects of these practices on intensive care unit mortality. DESIGN: Subanalysis of a prospective observational study. Multivariable logistic regression was used to analyze the effects of ventilatory management on mortality. SETTING: A total of 361 intensive care units in 20 countries in March 1998. PATIENTS: A total of 467 mechanically ventilated patients with ARDS. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The mean tidal volume used in the first week of ARDS was 8.8 mL/kg measured body weight, and there was great variability in these tidal volumes (sd = 2.0). Tidal volumes were significantly lower in patients with (n = 265) than without (n = 202) a recorded plateau pressure (8.6 vs. 9.1 mL/kg, p = .01). The overall intensive care unit mortality rate was 60.2%. In addition to the strong influence of organ failures and higher levels of inspired oxygen, late-onset ARDS (onset after >48 hrs of mechanical ventilation; odds ratio, 2.09) was independently associated with mortality. In addition, lower levels of positive end-expiratory pressure were independently associated with higher mortality (odds ratio, 0.91; 1 cm of H2O increments). Neither inspiratory pressures nor tidal volumes were independently associated with mortality, and there was no evidence of increased mortality with the use of lower inspiratory pressures. CONCLUSIONS: This descriptive study demonstrated considerable interpatient variability in tidal volumes during the study period. In addition to traditional prognostic indicators, timing of ARDS onset and the use of low levels of positive end-expiratory pressure or no positive end-expiratory pressure during the first week may adversely influence outcome in ARDS patients.

Adult↗

Protocols for lung protective ventilation.

Protocols have a well-established role in clinical research and are increasingly being used to direct routine clinical care. In this article, we review the differing goals of research and clinical protocols and outline the similar process for their development. We use the mechanical ventilation protocol of the ARDS Network trial comparing small with traditional tidal volumes as an example. As a starting point for debate, we also suggest guiding principles and specific components of a protocol for high-frequency oscillatory ventilation.

High-Frequency Ventilation↗

Pre-B-cell colony-enhancing factor as a potential novel biomarker in acute lung injury.

Although the pathogenic and genetic basis of acute lung injury (ALI) remains incompletely understood, the identification of novel ALI biomarkers holds promise for unique insights. Expression profiling in animal models of ALI (canine and murine) and human ALI detected significant expression of pre-B-cell colony-enhancing factor (PBEF), a gene not previously associated with lung pathophysiology. These results were validated by real-time polymerase chain reaction and immunohistochemistry studies, with PBEF protein levels significantly increased in both bronchoalveolar lavage fluid and serum of ALI models and in cytokine- or cyclic stretch-activated lung microvascular endothelium. We genotyped two PBEF single-nucleotide polymorphisms (SNPs) in a well characterized sample of white patients with sepsis-associated ALI, patients with severe sepsis, and healthy subjects and observed that carriers of the haplotype GC from SNPs T-1001G and C-1543T had a 7.7-fold higher risk of ALI (95% confidence interval 3.01-19.75, p < 0.001). The T variant from the SNP C-1543T resulted in a significant decrease in the transcription rate (1.8-fold; p < 0.01) by the reporter gene assay. Together, these results strongly indicate that PBEF is a potential novel biomarker in ALI and demonstrate the successful application of robust genomic technologies in the identification of candidate genes in complex lung disease.

Adult↗

Higher versus lower positive end-expiratory pressures in patients with the acute respiratory distress syndrome.

BACKGROUND: Most patients requiring mechanical ventilation for acute lung injury and the acute respiratory distress syndrome (ARDS) receive positive end-expiratory pressure (PEEP) of 5 to 12 cm of water. Higher PEEP levels may improve oxygenation and reduce ventilator-induced lung injury but may also cause circulatory depression and lung injury from overdistention. We conducted this trial to compare the effects of higher and lower PEEP levels on clinical outcomes in these patients. METHODS: We randomly assigned 549 patients with acute lung injury and ARDS to receive mechanical ventilation with either lower or higher PEEP levels, which were set according to different tables of predetermined combinations of PEEP and fraction of inspired oxygen. RESULTS: Mean (+/-SD) PEEP values on days 1 through 4 were 8.3+/-3.2 cm of water in the lower-PEEP group and 13.2+/-3.5 cm of water in the higher-PEEP group (P<0.001). The rates of death before hospital discharge were 24.9 percent and 27.5 percent, respectively (P=0.48; 95 percent confidence interval for the difference between groups, -10.0 to 4.7 percent). From day 1 to day 28, breathing was unassisted for a mean of 14.5+/-10.4 days in the lower-PEEP group and 13.8+/-10.6 days in the higher-PEEP group (P=0.50). CONCLUSIONS: These results suggest that in patients with acute lung injury and ARDS who receive mechanical ventilation with a tidal-volume goal of 6 ml per kilogram of predicted body weight and an end-inspiratory plateau-pressure limit of 30 cm of water, clinical outcomes are similar whether lower or higher PEEP levels are used.

Adult↗

Low caloric intake is associated with nosocomial bloodstream infections in patients in the medical intensive care unit.

OBJECTIVE: To determine whether caloric intake is associated with risk of nosocomial bloodstream infection in critically ill medical patients. DESIGN: Prospective cohort study. SETTING: Urban, academic medical intensive care unit. PATIENTS: Patients were 138 adult patients who did not take food by mouth for > or =96 hrs after medical intensive care unit admission. MEASUREMENTS: Daily caloric intake was recorded for each patient. Participants subsequently were grouped into one of four categories of caloric intake: <25%, 25-49%, 50-74%, and > or =75% of average daily recommended calories based on the American College of Chest Physicians guidelines. Simplified Acute Physiology Score II and serum albumin were measured on medical intensive care unit admission. Serum glucose (average value and maximum value each day) and route of feeding (enteral, parenteral, or both) were collected daily. Nosocomial bloodstream infections were identified by infection control surveillance methods. MAIN RESULTS: The overall mean (+/-sd) daily caloric intake for all study participants was 49.4 +/- 29.3% of American College of Chest Physicians guidelines. Nosocomial bloodstream infection occurred in 31 (22.4%) participants. Bivariate Cox analysis revealed that receiving > or =25% of recommended calories compared with <25% was associated with significantly lower risk of bloodstream infection (relative hazard, 0.24; 95% confidence interval, 0.10-0.60). Simplified Acute Physiology Score II also was associated with risk of nosocomial bloodstream infection (relative hazard, 1.27; 95% confidence interval, 1.01-1.60). Average daily serum glucose, admission serum albumin, time to initiating nutritional support, and route of nutrition did not affect risk of bloodstream infection. After adjustment for Simplified Acute Physiology Score II in a multivariable analysis, receiving > or =25% of recommended calories was associated with a significantly lower risk of bloodstream infection (relative hazard, 0.27; 95% confidence interval, 0.11-0.68). CONCLUSIONS: In the context of reducing risk of nosocomial bloodstream infections, failing to provide > or =25% of the recommended calories may be harmful. Higher caloric goals may be necessary to achieve other clinically important outcomes.

Cohort Studies↗

Lung-protective ventilation strategies in acute lung injury.

OBJECTIVES: To review the challenges of providing mechanical ventilatory support for respiratory failure while avoiding ventilator-associated lung injury in patients with acute lung injury. To review the results of several randomized clinical trials of lung-protective ventilation strategies using conventional mechanical ventilators. DATA SOURCES: Published reports of clinical trials comparing clinical outcomes of patients with acute lung injury, randomized to mechanical ventilation with either a lung-protective or a control, conventional, standard, or traditional approach. DATA EXTRACTION AND SYNTHESIS: Lung-protective mechanical ventilation strategies are designed to prevent injury from overdistention by using lower tidal volumes and lower inspiratory pressures (volume- and pressure-limited ventilation) or injury from ventilation with atelectasis and alveolar flooding at end-expiration (open-lung ventilation). In one trial, clinical outcomes were better in the study group that received combined volume- and pressure-limited and open-lung strategies compared with the study group that received a conventional approach. Of four trials focusing on volume- and pressure-limited ventilation alone, three did not demonstrate improvements in clinical outcomes, whereas one demonstrated a substantial reduction in mortality and an increase in ventilator-free days. The different results in these four trials may be attributable to differences in tidal volumes between the study groups, chance variation, or differences in the management of respiratory acidosis. CONCLUSIONS: Evidence supports the use of a volume- and pressure-limited approach to mechanical ventilation in patients with acute lung injury. It is not yet clear whether the open-lung approach will further reduce mortality in patients receiving volume- and pressure-limited ventilation support.

Humans↗

Incidence of acute lung injury in the United States.

OBJECTIVE: Recent estimates of acute respiratory distress syndrome (ARDS) incidence have varied from 1.3 to 22 per 100,000 person years (105 person.years); the incidence of acute lung injury (ALI) has varied from 17.9 to 34 cases per 105 person.years. Potential reasons for this wide range include differences in the definition of the syndrome, in the populations sampled, and in the assumptions made to estimate incidence. We hypothesized that careful, prospective, protocol-driven case identification that included the milder hypoxemia criterion for ALI would yield incidence numbers greater than previously reported. DESIGN: Prospective cohort study with extrapolation to the U.S. population. SETTING: National Heart, Lung, and Blood Institute-sponsored ARDS Network composed of 20 hospitals. PATIENTS: As part of the National Institutes of Health-sponsored ARDS network, 20 hospitals prospectively identified patients with ALI from 1996 to 1999. Screening logs from this study were used to estimate ALI rates per intensive care unit (ICU) bed per year. We used the registry and data from the American Hospital Association to estimate the incidence of ALI in the United States. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The ALI per ICU bed incidence in the ARDS network registry varied from 0.7 to 5.8 cases of ALI per ICU bed per year with an average of 2.2 cases of ALI per ICU bed per year. We tested the robustness of the incidence estimate by performing a variety of sensitivity analyses. When we used the conservative assumptions that the ARDS network screening logs were complete at each of the participating hospitals and that ALI cases are limited to academic hospitals with > or =20 adult ICU beds, the incidence of ALI in adults in the United States is 22.4 cases per 105 person.years. Under the less conservative assumption that ALI cases occurred only at hospitals with > or =20 ICU beds, regardless of their academic status, the incidence of ALI in the United States is estimated at 64.2 cases per 105 person.years. CONCLUSIONS: Based on this analysis, which used prospective clinical trial screening data and conservative assumptions about where patients with ALI are cared for, the incidence of ALI in the United States appears to be higher than previously reported.

Humans↗

Effects of recruitment maneuvers in patients with acute lung injury and acute respiratory distress syndrome ventilated with high positive end-expiratory pressure.

OBJECTIVE: Positive end-expiratory pressure (PEEP) and recruitment maneuvers (RMs) may partially reverse atelectasis and reduce ventilation-associated lung injury. The purposes of this study were to assess a) magnitude and duration of RM effects on arterial oxygenation and on requirements for oxygenation support (Fio2/PEEP) in patients with acute lung injury and acute respiratory distress syndrome (ALI/ARDS) receiving ventilation with low tidal volumes and high levels of PEEP; and b) frequency of adverse respiratory and circulatory events attributable to RMs. DESIGN: Prospective, randomized, crossover study. SETTING: Thirty-four intensive care units at 19 hospitals. PATIENTS: Seventy-two patients with early ALI/ARDS. Baseline PEEP and Fio2 were 13.8 +/- 3.0 cm H2O and 0.39 +/- 0.10, respectively (mean +/- sd). INTERVENTIONS: We conducted RMs by applying continuous positive airway pressure of 35-40 cm H2O for 30 secs. We conducted sham RMs on alternate days. We monitored oxyhemoglobin saturation by pulse oximetry (SpO2), Fio2/PEEP, blood pressure, and heart rate for 8 hrs after RMs and sham RMs. We examined chest radiographs for barotrauma. MEASUREMENTS AND MAIN RESULTS: Responses to RMs were variable. Greatest increments from baseline SpO2 within 10 mins after RMs were larger than after sham RMs (1.7 +/- 0.2 vs. 0.6 +/- 0.3 %, mean +/- SEM, p < .01). Systolic blood pressure decreased more +/- 1.1 mm Hg, p < .01). Changes in Fio2/PEEP requirements were not significantly different at any time after RMs vs. sham RMs. Barotrauma was apparent on first radiographs after one RM and one sham RM. CONCLUSIONS: In ALI/ARDS patients receiving mechanical ventilation with low tidal volumes and high PEEP, short-term effects of RMs as conducted in this study are variable. Beneficial effects on gas exchange in responders appear to be of brief duration. More information is needed to determine the role of recruitment maneuvers in the management of ALI/ARDS.

Blood Pressure↗

Caloric intake in medical ICU patients: consistency of care with guidelines and relationship to clinical outcomes.

STUDY OBJECTIVES: To assess the consistency of caloric intake with American College of Chest Physicians (ACCP) recommendations for critically ill patients and to evaluate the relationship of caloric intake with clinical outcomes. DESIGN: Prospective cohort study. SETTING: Adult ICUs at two teaching hospitals. PARTICIPANTS: Patients with an ICU length of stay of at least 96 h. MEASUREMENTS AND RESULTS: On ICU admission, severity of illness (ie, simplified acute physiology score II) and markers of nutritional status (ie, serum albumin level and body mass index) were recorded. The route of feeding (ie, enteral or parenteral), actual caloric intake (ie, percentage of ACCP recommendations: 0 to 32% [tertile I]; 33 to 65% [tertile II]; >/==" BORDER="0"> 66% [tertile III]), and evidence of GI intolerance (ie, gastric aspirate levels, >/==" BORDER="0"> 100 mL) were recorded daily. The following outcomes were assessed: status on hospital discharge (alive vs dead); spontaneous ventilation before ICU discharge (yes vs no); and ICU discharge without developing nosocomial sepsis (yes vs no). The average caloric intake among 187 participants was 50.6% of the ACCP targets and was similar in both hospitals. Caloric intake was inversely related to the mean number of gastric aspirates >/==" BORDER="0"> 100 mL/d (Spearman rho = -0.04; p = 0.06), but not to severity of illness, nutritional status, or route of feeding. After accounting for the number of gastric aspirates >/==" BORDER="0"> 100 mL, severity of illness, nutritional status, and route of feeding, tertile II of caloric intake (vs tertile I) was associated with a significantly greater likelihood of achieving spontaneous ventilation prior to ICU discharge. Tertile III of caloric intake (vs tertile I) was associated with a significantly lower likelihood of both hospital discharge alive and spontaneous ventilation prior to ICU discharge. CONCLUSIONS: Study participants were underfed relative to ACCP targets. These targets, however, may overestimate needs, since moderate caloric intake (ie, 33 to 65% of ACCP targets; approximately 9 to 18 kcal/kg per day) was associated with better outcomes than higher levels of caloric intake.

APACHE↗

Effectiveness of medical resident education in mechanical ventilation.

Specific methods of mechanical ventilation management reduce mortality and lower health care costs. However, in the face of a predicted deficit of intensivists, it is unclear whether residency programs are training internists to provide effective care for patients who require mechanical ventilation. To evaluate these educational outcomes, we administered a validated 19-item case-based test and survey to resident physicians at 31 diverse U.S. internal medicine residency programs nationwide. Of 347 senior residents, 259 (75%) responded. The mean test score was 74% correct (SD, 14%; range, 37 to 100%). Important items representing evidence-based standards of critical care answered incorrectly were as follows: use of appropriate tidal volume in the acute respiratory distress syndrome (48% incorrect), identifying a patient ready for a weaning trial (38% incorrect), and recognizing indication for noninvasive ventilation (27% incorrect). Most accurately identified pneumothorax (86% correct) and increased intrathoracic positive end-expiratory pressure (93% correct). Better scores were associated with "closed" versus "open" intensive care unit organization (76 versus 71% correct, p = 0.001), resident perception of greater versus lesser ventilator knowledge (79 versus 71% correct, p = 0.001), and graduation from a U.S. versus international medical school (75 versus 69% correct, p = 0.033). Although overall training satisfaction correlated strongly with program use of learning objectives (r = 0.89, p < 0.0001), only 46% reported being satisfied with their mechanical ventilation training. We conclude that senior residents may not be gaining essential evidence-based knowledge needed to provide effective care for patients who require mechanical ventilation. Residency programs should emphasize evidence-based learning objectives to guide mechanical ventilation instruction.

Educational Measurement↗

Vancomycin-sensitive and vancomycin-resistant enterococcal infections in the ICU: attributable costs and outcomes.

OBJECTIVES: To determine the economic and clinical outcomes associated with infection with vancomycin-resistant Enterococcus (VRE) and to compare these outcomes to those associated with infection with vancomycin-sensitive Enterococcus (VSE). METHODS: During a 3-month, prospective, cohort study of 117 high-risk, critically ill patients we collected complete clinical and demographic and ICU cost data from all patients during their ICU stays. RESULTS: After adjusting for variables in a stepwise multiple regression model VRE infections were associated with a median attributable increased ICU cost per patient of $33,251 (38,088 euros) and an increased length of hospital stay (LOS) of 22 days, while VSE infections were associated with an increased cost of $21,914 (25,102 euros) and an increased LOS of 27 days. The effect of VRE and VSE infections were not significantly different. Over the entire cohort the attributable cost per ICU patient day associated with VRE infection was $304 (348 euros). CONCLUSIONS: The attributable cost of ICU care associated with VRE infection is $33,251 (38,088 euros) and per ICU patient day was $304 (348 euros). VRE and VSE infections do not differ in associated cost of ICU care, LOS, or mortality. Any VRE control strategy is be cost-effective if the overall cost per ICU patient-day is less than $304 (348 euros).

APACHE↗