John Granton

Evaluation of A ventilation strategy to prevent barotrauma in patients at high risk for acute respiratory distress syndrome

BACKGROUND A strategy of mechanical ventilation that limits airway pressure and tidal volume while permitting hypercapnia has been recommended for patients with the acute respiratory distress syndrome. The goal is to reduce lung injury due to overdistention. However, the efficacy of this approach has not been established. METHODS Within 24 hours of intubation, patients at high risk for the acute respiratory distress syndrome were randomly assigned to either pressure- and volume-limited ventilation (limited-ventilation group), with the peak inspiratory pressure maintained at 30 cm of water or less and the tidal volume at 8 ml per kilogram of body weight or less, or to conventional ventilation (control group), with the peak inspiratory pressure allowed to rise as high as 50 cm of water and the tidal volume at 10 to 15 ml per kilogram. All other ventilatory variables were similar in the two groups. RESULTS A total of 120 patients with similar clinical features underwent randomization (60 in each group). The patients in the limited-ventilation and control groups were exposed to different mean (+/-SD) tidal volumes (7.2+/-0.8 vs. 10.8+/-1.0 ml per kilogram, respectively; P<0.001) and peak inspiratory pressures (23.6+/-5.8 vs. 34.0+/-11.0 cm of water, P<0.001). Mortality was 50 percent in the limited-ventilation group and 47 percent in the control group (relative risk, 1.07; 95 percent confidence interval, 0.72 to 1.57; P=0.72). In the limited-ventilation group, permissive hypercapnia (arterial carbon dioxide tension, >50 mm Hg) was more common (52 percent vs. 28 percent, P=0.009), more marked (54.4+/-18.8 vs. 45.7+/-9.8 mm Hg, P=0.002), and more prolonged (146+/-265 vs. 25+/-22 hours, P=0.017) than in the control group. The incidence of barotrauma, the highest multiple-organ-dysfunction score, and the number of episodes of organ failure were similar in the two groups; however, the numbers of patients who required paralytic agents (23 vs. 13, P=0.05) and dialysis for renal failure (13 vs. 5, P= 0.04) were greater in the limited-ventilation group than in the control group. CONCLUSIONS In patients at high risk for the acute respiratory distress syndrome, a strategy of mechanical ventilation that limits peak inspiratory pressure and tidal volume does not appear to reduce mortality and may increase morbidity.

Long-term follow-up of survivors of acute lung injury: lack of effect of a ventilation strategy to prevent barotrauma.

OBJECTIVES To determine the effect of a ventilation strategy to prevent barotrauma on long-term outcome in survivors of acute lung injury. DESIGN Prospective blinded cohort analysis. SETTING Three university-affiliated medical-surgical intensive care units. PATIENTS A total of 28 survivors of acute lung injury, 1-2 yrs after diagnosis, from a multicenter prospective randomized controlled trial comparing pressure (peak inflation pressure < or =30 cm H2O) and volume (tidal volume < or =8 mL/kg) limited ventilation to a conventional (peak inflation pressure < or =50 cm H2O, tidal volume 10-15 mL/kg) ventilation strategy. MEASUREMENTS AND MAIN RESULTS Physicians blinded as to treatment group evaluated 20 of 28 survivors (treatment group, 7; control group, 13). Exercise tolerance in the 6-minute walk test was comparable to patients with chronic respiratory disease and equivalent between groups (treatment group, 373+/-171 m vs. control group, 375+/-129 m; p = .84). Pulmonary function testing showed reduced diffusing capacity (treatment group, 64+/-29% predicted vs. control group, 74+/-14% predicted; p = .68) and normal volumes, flows, and blood gases. Two domains of disease-specific Health Related Quality of Life assessed by the Chronic Respiratory Questionnaire were worse for patients in the treatment group compared with the control group (Emotional Function 3.8+/-1.4 vs. 5.1+/-0.08; p = .05, Mastery 4.7+/-1.7 vs. 6.2+/-0.8; p = .03). There were no between-group differences in the scores of the Spitzer Quality of Life Index (a generic Health Related Quality of Life instrument), although they were reduced (7.5+/-1.9) and comparable to patients with chronic disease. CONCLUSIONS We found that 1-2 yrs after the onset of their illness, survivors of acute lung injury have reductions in quality of life and exercise tolerance which are similar to patients with chronic diseases. We were unable to show that a limited ventilation strategy improves either long-term pulmonary function or quality of life in survivors of acute lung injury.

Oxygenation Response to Positive End-Expiratory Pressure Predicts Mortality in Acute Respiratory Distress Syndrome. A Secondary Analysis of the LOVS and ExPress Trials

RATIONALE Previous trials of higher positive end-expiratory pressure (PEEP) for acute respiratory distress syndrome (ARDS) failed to demonstrate mortality benefit, possibly because of differences in lung recruitability among patients with ARDS. OBJECTIVES To determine whether the physiological response to increased PEEP is associated with mortality. METHODS In a secondary analysis of the Lung Open Ventilation Study (LOVS, n = 983), we examined the relationship between the initial response to changes in PEEP after randomization and mortality. We sought to corroborate our findings using data from a different trial of higher PEEP (ExPress, n = 749). MEASUREMENTS AND MAIN RESULTS The oxygenation response (change in ratio of arterial partial pressure of oxygen to fraction of inspired oxygen: P/F) after the initial change in PEEP after randomization varied widely (median, 9.5 mm Hg; interquartile range, -16 to 47) and was only weakly related to baseline P/F or the magnitude of PEEP change. Among patients in whom PEEP was increased after randomization, an increase in P/F was associated with reduced mortality (multivariable logistic regression; adjusted odds ratio, 0.80 [95% confidence interval, 0.72-0.89] per 25-mm Hg increase in P/F), particularly in patients with severe disease (baseline P/F [less-than-or-equal-to] 150 mm Hg). Changes in compliance and dead space were not associated with mortality. These findings were confirmed by a similar analysis of data from the ExPress trial. CONCLUSIONS Patients with ARDS who respond to increased PEEP by improved oxygenation have a lower risk of death. The oxygenation response to PEEP might be used to predict whether patients will benefit from higher versus lower PEEP.

Right heart characteristics and exercise parameters in adults with Ebstein anomaly: New perspectives from cardiac magnetic resonance imaging studies

BACKGROUND The utility of cardiac magnetic resonance imaging (CMR) for assessment of adults with Ebstein anomaly is not well-defined. We sought to evaluate CMR characteristics in this population and to relate these to exercise parameters. METHODS We analyzed CMR studies in adults with unrepaired Ebstein anomaly for measures of severity of Ebstein disease, including atrialized, functional and total right ventricular (RV) volumes, ejection fraction (EF) and severity index (area of atrialized RV+right atrium/functional RV+left ventricle+left atrium). We related these CMR values to cardiopulmonary exercise test measurements. RESULTS Twenty-seven adults (mean age 41 ± 14 years, 70% female) were included. Functional RV end-diastolic volume (EDV) was 150 ± 68 mL/m(2) and atrialized RVEDV was 25 ± 24 mL/m(2). In 17 patients (63%), the functional RVEDV was enlarged (>114 mL/m(2)). Percent predicted peak VO2 for the population was 65 ± 20%. On univariable analysis, peak VO2 was inversely related to atrialized RVEDV (p = 0.011), total RVEDV (p = 0.041), functional RVEDV/left ventricular EDV ratio (p = 0.015) and magnitude of tricuspid valve displacement (p = 0.031). In the multivariate model, the only CMR factor to relate to peak VO2 was atrialized RVEDV (p = 0.011, β = -0.48). No significant correlations were found between CMR measures and heart rate response or ventilatory response to exercise. CONCLUSION In adults with unrepaired Ebstein anomaly, atrialized RV volume was independently related to aerobic capacity. The volume of the atrialized RV is a novel CMR measure which may express severity of disease. Further research is needed to evaluate the prognostic relevance of this exploratory work.

Prophylaxis against venous thromboembolism in neurointensive care patients: Survey of Canadian practice

PURPOSE Although anticoagulant thromboprophylaxis reduces the incidence of venous thromboembolism in critically ill patients, it may increase the risk of devastating bleeding complications in neurosurgical patients. For this population, anticoagulant thromboprophylaxis remains controversial and randomized controlled studies are sparse. Our goal was to establish sufficient clinical equipoise to facilitate future research in this area. MATERIALS AND METHODS We conducted a survey of Canadian neurosurgeons and neurointensivists to better understand current practice. We developed a novel self-administered questionnaire on anticoagulant thromboprophylaxis for different neurosurgical subgroups using illustrative clinical scenarios. The instrument was evaluated for clinical sensibility by 20 nurses, neurosurgeons, and intensivists and then mailed to Canadian neurosurgeons (Canadian Neurosurgery Society) and intensivists (Canadian Critical Care Society). RESULTS The response rate after 3 mailings was 50% for neurosurgeons (66/132) and 49% for intensivists (94/193). Most respondents reported use of anticoagulant thromboprophylaxis for neurosurgical patients, although the timing varied considerably. Use of anticoagulant thromboprophylaxis (ever) ranged from 60% for traumatic intracranial hemorrhage after decompressive craniotomy to 90% for traumatic spinal injury. The responses were comparable between specialties. CONCLUSIONS Most Canadian physicians reported using anticoagulant thromboprophylaxis after neurosurgery, although practice patterns differed as to when and for whom. Future research should quantify the benefits and risks in relation to the time of initiation in different neurosurgical subgroups. Our results suggest there is equipoise regarding the use of anticoagulation thromboprophylaxis in neurosurgical patients. Therefore randomized controlled trials are justifiable and needed to guide clinicians.

Prophylactic anticoagulation to prevent venous thromboembolism in traumatic intracranial hemorrhage: a decision analysis

IntroductionPatients with intracranial hemorrhage due to traumatic brain injury are at high risk of developing venous thromboembolism including deep vein thrombosis (DVT) and pulmonary embolism (PE). Thus, there is a trade-off between the risks of progression of intracranial hemorrhage (ICH) versus reduction of DVT/PE with the use of prophylactic anticoagulation. Using decision analysis modeling techniques, we developed a model for examining this trade-off for trauma patients with documented ICH.MethodsThe decision node involved the choice to administer or to withhold low molecular weight heparin (LMWH) anticoagulation prophylaxis at 24 hours. Advantages of withholding therapy were decreased risk of ICH progression (death, disabling neurologic deficit, non-disabling neurologic deficit), and decreased risk of systemic bleeding complications (death, massive bleed). The associated disadvantage was greater risk of developing DVT/PE or death. Probabilities for each outcome were derived from natural history studies and randomized controlled trials when available. Utilities were obtained from accepted databases and previous studies.ResultsThe expected value associated with withholding anticoagulation prophylaxis was similar (0.90) to that associated with the LMWH strategy (0.89). Only two threshold values were encountered in one-way sensitivity analyses. If the effectiveness of LMWH at preventing DVT exceeded 80% (range from literature 33% to 82%) our model favoured this therapy. Similarly, our model favoured use of LMWH if this therapy increased the risk of ICH progression by no more than 5% above the baseline risk.ConclusionsOur model showed no clear advantage to providing or withholding anticoagulant prophylaxis for DVT/PE prevention at 24 hours after traumatic brain injury associated with ICH. Therefore randomized controlled trials are justifiable and needed to guide clinicians.

Critical care capacity in Canada: results of a national cross-sectional study

IntroductionIntensive Care Units (ICUs) provide life-supporting treatment; however, resources are limited, so demand may exceed supply in the event of pandemics, environmental disasters, or in the context of an aging population. We hypothesized that comprehensive national data on ICU resources would permit a better understanding of regional differences in system capacity.MethodsAfter the 2009–2010 Influenza A (H1N1) pandemic, the Canadian Critical Care Trials Group surveyed all acute care hospitals in Canada to assess ICU capacity. Using a structured survey tool administered to physicians, respiratory therapists and nurses, we determined the number of ICU beds, ventilators, and the ability to provide specialized support for respiratory failure.ResultsWe identified 286 hospitals with 3170 ICU beds and 4982 mechanical ventilators for critically ill patients. Twenty-two hospitals had an ICU that routinely cared for children; 15 had dedicated pediatric ICUs. Per 100,000 population, there was substantial variability in provincial capacity, with a mean of 0.9 hospitals with ICUs (provincial range 0.4-2.8), 10 ICU beds capable of providing mechanical ventilation (provincial range 6–19), and 15 invasive mechanical ventilators (provincial range 10–24). There was only moderate correlation between ventilation capacity and population size (coefficient of determination (R2) = 0.771).ConclusionICU resources vary widely across Canadian provinces, and during times of increased demand, may result in geographic differences in the ability to care for critically ill patients. These results highlight the need to evolve inter-jurisdictional resource sharing during periods of substantial increase in demand, and provide background data for the development of appropriate critical care capacity benchmarks.

Riociguat for the treatment of pulmonary hypertension.

Nitric oxide (NO) is a critical signaling molecule in the pulmonary vasculature. NO activates soluble guanylate cyclase (sGC) resulting in the synthesis of cyclic guanosine monophosphate (cGMP) – a key mediator of pulmonary artery vasodilatation that may also inhibit smooth muscle proliferation and platelet aggregation. Pulmonary hypertension, a serious, progressive and often fatal disease is characterized by NO-sGC-sGMP pathway dysregulation. Riociguat is a member of a novel therapeutic class known as soluble guanylate stimulators. Riociguat has a dual mode of action, acting in synergy with endogenous NO and also directly stimulating sGC independently of NO availability. Phase 3 randomized control trials have demonstrated that riociguat improves clinical, physiologic and hemodynamic parameters in patients with pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension. In this review we will discuss the pharmacologic properties of riociguat and its appropriate implementation into clinical practice.

Pharmacology of the Pulmonary Circulation

The pulmonary vasculature is a complex system and studies of the effects of anesthetic drugs on this system are often contradictory. A balanced anesthetic technique with adherence to the hemodynamic goals of maintenance of right ventricular preload and right coronary perfusion is the safest choice for patients with PHTN. There are no absolute contraindications to most anesthetic drugs in patients with pulmonary hypertension. Inhaled pulmonary vasodilators can be used to optimize hemodynamic variables perioperatively, although effects on gas exchange are variable.

The screen log: a tool for monitoring critical care clinical research activity.

Clinical research relevant to the care of critically ill patients has been ongoing for decades. Sponsors of research projects monitor site performance by providing a screen log (SL) which contains a record of enrolled patients (multicentre, uni-project in scope). The present study was undertaken to evaluate the utility of a unicentre, multi-project SL.