Rolf D. Hubmayr

Silver-coated endotracheal tubes and incidence of ventilator-associated pneumonia: The NASCENT randomized trial

CONTEXT Ventilator-associated pneumonia (VAP) causes substantial morbidity. A silver-coated endotracheal tube has been designed to reduce VAP incidence by preventing bacterial colonization and biofilm formation. OBJECTIVE To determine whether a silver-coated endotracheal tube would reduce the incidence of microbiologically confirmed VAP. DESIGN, SETTING, AND PARTICIPANTS Prospective, randomized, single-blind, controlled study conducted in 54 centers in North America. A total of 9417 adult patients (> or = 18 years) were screened between 2002 and 2006. A total of 2003 patients expected to require mechanical ventilation for 24 hours or longer were randomized. INTERVENTION Patients were assigned to undergo intubation with 1 of 2 high-volume, low-pressure endotracheal tubes, similar except for a silver coating on the experimental tube. MAIN OUTCOME MEASURES Primary outcome was VAP incidence based on quantitative bronchoalveolar lavage fluid culture with 10(4) colony-forming units/mL or greater in patients intubated for 24 hours or longer. Other outcomes were VAP incidence in all intubated patients, time to VAP onset, length of intubation and duration of intensive care unit and hospital stay, mortality, and adverse events. RESULTS Among patients intubated for 24 hours or longer, rates of microbiologically confirmed VAP were 4.8% (37/766 patients; 95% confidence interval [CI], 3.4%-6.6%) in the group receiving the silver-coated tube and 7.5% (56/743; 95% CI, 5.7%-9.7%) (P = .03) in the group receiving the uncoated tube (all intubated patients, 3.8% [37/968; 95% CI, 2.7%-5.2%] and 5.8% [56/964; 95% CI, 4.4%-7.5%] [P = .04]), with a relative risk reduction of 35.9% (95% CI, 3.6%-69.0%; all intubated patients, 34.2% [95% CI, 1.2%-67.9%]). The silver-coated endotracheal tube was associated with delayed occurrence of VAP (P = .005). No statistically significant between-group differences were observed in durations of intubation, intensive care unit stay, and hospital stay; mortality; and frequency and severity of adverse events. CONCLUSION Patients receiving a silver-coated endotracheal tube had a statistically significant reduction in the incidence of VAP and delayed time to VAP occurrence compared with those receiving a similar, uncoated tube. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00148642.

Transfusion related acute lung injury: incidence and risk factors

Transfusion-related acute lung injury (TRALI) is the leading cause of transfusion-related mortality. To determine TRALI incidence by prospective, active surveillance and to identify risk factors by a case-control study, 2 academic medical centers enrolled 89 cases and 164 transfused controls. Recipient risk factors identified by multivariate analysis were higher IL-8 levels, liver surgery, chronic alcohol abuse, shock, higher peak airway pressure while being mechanically ventilated, current smoking, and positive fluid balance. Transfusion risk factors were receipt of plasma or whole blood from female donors (odds ratio = 4.5, 95% confidence interval [CI], 1.85-11.2, P = .001), volume of HLA class II antibody with normalized background ratio more than 27.5 (OR = 1.92/100 mL, 95% CI, 1.08-3.4, P = .03), and volume of anti-human neutrophil antigen positive by granulocyte immunofluoresence test (OR = 1.71/100 mL, 95% CI, 1.18-2.5, P = .004). Little or no risk was associated with older red blood cell units, noncognate or weak cognate class II antibody, or class I antibody. Reduced transfusion of plasma from female donors was concurrent with reduced TRALI incidence: 2.57 (95% CI, 1.72-3.86) in 2006 versus 0.81 (95% CI, 0.44-1.49) in 2009 per 10 000 transfused units (P = .002). The identified risk factors provide potential targets for reducing residual TRALI.

Stretch induces cytokine release by alveolar epithelial cells in vitro

Mechanical ventilation can injure the lung, causing edema and alveolar inflammation. Interleukin-8 (IL-8) plays an important role in this inflammatory response. We postulated that cyclic cell stretch upregulates the production and release of IL-8 by human alveolar epithelium in the absence of structural cell damage or paracrine stimulation. To test this hypothesis, alveolar epithelial cells (A549 cells) were cultured on a deformable silicoelastic membrane. When stretched by 30% for up to 48 h, the cells released 49 ± 34% more IL-8 ( P < 0.001) than static controls. Smaller deformations (20% stretch) produced no consistent increase in IL-8. Stretch of 4 h duration increased IL-8 gene transcription fourfold above baseline. Stretch had no effect on cell proliferation, cell viability as assessed by51Cr release assay, or the release of granulocyte-macrophage colony-stimulating factor and tumor necrosis factor-α. We conclude that deformation per se can trigger inflammatory signaling and that alveolar epithelial cells may be active participants in the alveolitis associated with ventilator-induced lung injury.

Intraoperative Tidal Volume as a Risk Factor for Respiratory Failure after Pneumonectomy

Background:Respiratory failure is a leading cause of postoperative morbidity and mortality in patients undergoing pneumonectomy. The authors hypothesized that intraoperative mechanical ventilation with large tidal volumes (VTs) would be associated with increased risk of postpneumonectomy respiratory failure. Methods:Patients undergoing elective pneumonectomy at the authors’ institution from January 1999 to January 2003 were studied. The authors collected data on demographics, relevant comorbidities, neoadjuvant therapy, pulmonary function tests, site and type of operation, duration of surgery, intraoperative ventilator settings, and intraoperative fluid administration. The primary outcome measure was postoperative respiratory failure, defined as the need for continuation of mechanical ventilation for greater than 48 h postoperatively or the need for reinstitution of mechanical ventilation after extubation. Results:Of 170 pneumonectomy patients who met inclusion criteria, 30 (18%) developed postoperative respiratory failure. Causes of postoperative respiratory failure were acute lung injury in 50% (n = 15), cardiogenic pulmonary edema in 17% (n = 5), pneumonia in 23% (n = 7), bronchopleural fistula in 7% (n = 2), and pulmonary thromboembolism in 3% (n = 1). Patients who developed respiratory failure were ventilated with larger intraoperative VT than those who did not (median, 8.3 vs. 6.7 ml/kg predicted body weight; P < 0.001). In a multivariate regression analysis, larger intraoperative VT (odds ratio, 1.56 for each ml/kg increase; 95% confidence interval, 1.12–2.23) was associated with development of postoperative respiratory failure. The interaction between larger VT and fluid administration was also statistically significant (odds ratio, 1.36; 95% confidence interval, 1.05–1.97). Conclusion:Mechanical ventilation with large intraoperative VT is associated with increased risk of postpneumonectomy respiratory failure.

Effect of 24-hour mandatory versus on-demand critical care specialist presence on quality of care and family and provider satisfaction in the intensive care unit of a teaching hospital*

Objective:The benefit of continuous on-site presence by a staff academic critical care specialist in the intensive care unit of a teaching hospital is not known. We compared the quality of care and patient/family and provider satisfaction before and after changing the staffing model from on-demand to continuous 24-hr critical care specialist presence in the intensive care unit. Design:Two-year prospective cohort study of patient outcomes, processes of care, and family and provider survey of satisfaction, organization, and culture in the intensive care unit. Setting:Intensive care unit of a teaching hospital. Patients:Consecutive critically ill patients, their families, and their caregivers. Interventions:Introduction of night-shift coverage to provide continuous 24-hr on-site, as opposed to on-demand, critical care specialist presence. Measurements and Main Results:Of 2,622 patients included in the study, 1,301 were admitted before and 1,321 after the staffing model change. Baseline characteristics and adjusted intensive care unit and hospital mortality were similar between the two groups. The nonadherence to evidence-based care processes improved from 24% to 16% per patient-day after the staffing change (p = .002). The rate of intensive care unit complications decreased from 11% to 7% per patient-day (p = .023). When adjusted for predicted hospital length of stay, admission source, and do-not-resuscitate status, hospital length of stay significantly decreased during the second period (adjusted mean difference −1.4, 95% confidence interval −0.3 to −2.5 days, p = .017). The new model was considered optimal for patient care by the majority of the providers (78% vs. 38% before the intervention, p < .001). Family satisfaction was excellent during both study periods (mean score 5.87 ± 1.7 vs. 5.95 ± 2.0, p = .777). Conclusions:The introduction of continuous (24-hr) on-site presence by a staff academic critical care specialist was associated with improved processes of care and staff satisfaction and decreased intensive care unit complication rate and hospital length of stay.

Pulmonary edema after transfusion: How to differentiate transfusion-associated circulatory overload from transfusion-related acute lung injury

Objective:Pulmonary edema is an underrecognized and potentially serious complication of blood transfusion. Distinct mechanisms include adverse immune reactions and circulatory overload. The former is associated with increased pulmonary vascular permeability and is commonly referred to as transfusion-related acute lung injury (TRALI). The latter causes hydrostatic pulmonary edema and is commonly referred to as transfusion-associated circulatory overload (TACO). In this review article we searched the National Library of Medicine PubMed database as well as references of retrieved articles and summarized the methods for differentiating between hydrostatic and permeability pulmonary edema. Results:The clinical and radiologic manifestations of TACO and TRALI are similar. Although echocardiography and B-type natriuretic peptide measurements may aid in the differential diagnosis between hydrostatic and permeability pulmonary edema, invasive techniques such as right heart catheterization and the sampling of alveolar fluid protein are sometimes necessary. The diagnostic differentiation is especially difficult in critically ill patients will multiple comorbidities so that the cause of edema may only be determined post hoc based on the clinical course and response to therapy. Guided by available evidence, we present an algorithm for establishing the pretest probability of TRALI as opposed to TACO. The decision to test donor and recipient blood for immunocompatibility may be made on this basis. Conclusions:The distinction between hydrostatic (TACO) and permeability (TRALI) pulmonary edema after transfusion is difficult, in part because the two conditions may coexist. Knowledge of strengths and limitations of different diagnostic techniques is necessary before initiation of complex TRALI workup.

The Impact of Morbid Obesity, Pneumoperitoneum, and Posture on Respiratory System Mechanics and Oxygenation During Laparoscopy

We studied the effect of morbid obesity, 20 mm Hg pneumoperitoneum, and body posture (30° head down and 30° head up) on respiratory system mechanics, oxygenation, and ventilation during laparoscopy. We hypothesized that insufflation of the abdomen with CO2 during laparoscopy would produce more impairment of respiratory system mechanics and gas exchange in the morbidly obese than in patients of normal weight. The static respiratory system compliance and inspiratory resistance were computed by using a Servo Screen pulmonary monitor. A continuous blood gas monitor was used to monitor real-time Paco2 and Pao2, and the ETco2 was recorded by mass spectrometry. Static compliance was 30% lower and inspiratory resistance 68% higher in morbidly obese supine anesthetized patients compared with normal-weight patients. Whereas body posture (head down and head up) did not induce additional large alterations in respiratory mechanics, pneumoperitoneum caused a significant decrease in static respiratory system compliance and an increase in inspiratory resistance. These changes in the mechanics of breathing were not associated with changes in the alveolar-to-arterial oxygen tension difference, which was larger in morbidly obese patients. Before pneumoperitoneum, morbidly obese patients had a larger ventilatory requirement than the normal-weight patients to maintain normocapnia (6.3 ± 1.4 L/min versus 5.4 ± 1.9 L/min, respectively;P = 0.02). During pneumoperitoneum, morbidly obese, supine, anesthetized patients had less efficient ventilation: a 100-mL increase of tidal volume reduced Paco2 on average by 5.3 mm Hg in normal-weight patients and by 3.6 mm Hg in morbidly obese patients (P = 0.02). In conclusion, respiratory mechanics during laparoscopy are affected by obesity and pneumoperitoneum but vary little with body position. The Pao2 was adversely affected only by increased body weight.

Statement of the 4th International Consensus Conference in Critical Care on ICU-Acquired Pneumonia – Chicago, Illinois, May 2002

International Consensus Conference Committee. ATS: Catherine Sassoon (Long Beach, Calif., USA), Brian Kavanagh (Toronto, Canada); ERS: Marc Elliott (Leeds, UK); ESICM: Graham Ramsay (Maastricht, Netherlands), Marco Ranieri (Turino, Italy); SRLF: Didier Dreyfuss (Paris, France), Jordi Mancebo (Barcelona, Spain) Scientific Experts: Edward Abraham (Denver, USA), Massimo Antonelli (Roma, Italy), Robert P. Baughman (Cincinnati, USA), Marc Bonten (Utrecht, Netherland), Lucca Brazzi (Italy), Jean Chastre (Paris, France), Deborah Cook (Hamilton, Canada), Donald E. Craven (Boston, USA), Lisa L. Dever (New Jersey, USA), Didier Dreyfuss (Colombes, France), Mahmoud Eltorky, (Memphis, USA), Jean-Yves Fagon (Paris, France), Jesse Hall (Chicago, USA), Alan M. Fein (Manhasset, USA), Dean Hess (Boston, USA), Steven H. Kirtland (Seattle, USA), Marin H. Kollef (St. Louis, USA), Lionel A. Mandell (Hamilton, Canada), Charles H. Marquette (Lille, France), Thomas R. Martin (Seattle, USA), C. Glen Mayhall (Galveston, USA), G. Umberto Meduri (Memphis, USA), Dominique L. Monnet (Copenhagen, Denmark), Michael S. Niederman (Mineola, USA), Jerome Pugin (Geneva, Switzerland), Theodore J. Standiford (Michigan, USA), Jordi Rello (Tarragona, Spain), Jean-François Timsit (Paris, France), Antonio Torres (Barcelona, Spain), Robert Weinstein (Chicago, USA), Richard Wunderink (Memphis, USA)

Toward the prevention of acute lung injury: Protocol-guided limitation of large tidal volume ventilation and inappropriate transfusion

Objective:We evaluated the effect of two quality improvement interventions (low tidal volume ventilation and restrictive transfusion) on the development of acute lung injury in mechanically ventilated patients. Design:Observational cohort study. Setting:Three intensive care units in a tertiary academic center. Patients:We included patients who were mechanically ventilated for ≥48 hrs excluding those who refused research authorization or had preexisting acute lung injury or pneumonectomy. Interventions:Multifaceted interdisciplinary intervention consisting of Web-based teaching, respiratory therapy protocol, and decision support within computerized order entry. Measurements and Main Results:Of 375 patients who met the inclusion and exclusion criteria, 212 were ventilated before and 163 after the interventions. Baseline characteristics were similar between the two groups except for a lower frequency of sepsis (27% vs. 17%, p = .030), trend toward lower median glucose level (140 mg/dL, interquartile range 118–168 vs. 132 mg/dL, interquartile range 113–156, p = .096), and lower frequency of pneumonia (27% vs. 20%, p = .130) during the second period. We observed a large decrease in tidal volume (10.6–7.7 mL/kg predicted body weight, p < .001), in peak airway pressure (31–25 cm H2O, p < .001), and in the percentage of transfused patients (63% to 38%, p < .001) after the intervention. The frequency of acute lung injury decreased from 28% to 10% (p < .001). The duration of mechanical ventilation decreased from a median of 5 (interquartile range 4–9) to 4 (interquartile range 4–8) days (p = .030). When adjusted for baseline characteristics in a multivariate logistic regression analysis, protocol intervention was associated with a reduction in the frequency of new acute lung injury (odds ratio 0.21, 95% confidence interval 0.10–0.40). Conclusions:Interdisciplinary intervention effectively decreased large tidal volumes and unnecessary transfusion in mechanically ventilated patients and was associated with a decreased frequency of new acute lung injury.

Risk factors for the development of acute lung injury in patients with septic shock : An observational cohort study

Objective:Almost half of the patients with septic shock develop acute lung injury (ALI). The understanding why some patients do and others do not develop ALI is limited. The objective of this study was to test the hypothesis that delayed treatment of septic shock is associated with the development of ALI. Design:Observational cohort study. Setting:Medical intensive care unit in a tertiary medical center. Patients:Prospectively identified patients with septic shock who did not have ALI at the outset, excluding those who denied research authorization. Measurements and Main Results:High frequency cardio-respiratory monitoring, arterial gas analysis, and portable chest radiographs were reviewed to identify the timing of ALI development. Risk factors present before ALI development were identified by review of electronic medical records and analyzed in univariate and multivariate analyses. Seventy-one of 160 patients (44%) developed ALI at a median of 5 (range 2–94) hours after the onset of septic shock. Multivariate logistic regression analysis identified the following predictors of ALI development: delayed goal-directed resuscitation (odds ratio [OR] 3.55, 95% confidence interval [CI] 1.52–8.63, p = .004), delayed antibiotics (OR 2.39, 95% CI 1.06 −5.59, p = .039), transfusion (OR 2.75, 95% CI 1.22–6.37, p = .016), alcohol abuse (OR 2.09, 95% CI .88−5.10, p = 0.098), recent chemotherapy (OR 6.47, 95% CI 1.99−24.9, p = 0.003), diabetes mellitus (OR .44, 95% CI .17−1.07, p = .076), and baseline respiratory rate (OR 2.03 per sd, 95% CI 1.38−3.08, p < .001). Conclusion:When adjusted for known modifiers of ALI expression, delayed treatment of shock and infection were associated with development of ALI.