Karen J. Bosma

High tidal volume is associated with the development of acute lung injury after severe brain injury : An international observational study

Objective:Although a significant number of patients with severe brain injury develop acute lung injury, only intracranial risk factors have previously been studied. We investigated the role of extracranial predisposing factors, including hemodynamic and ventilatory management, as independent predictors of acute lung injury in brain-injured patients. Design:Prospective multicenter observational study. Setting:Four European intensive care units in university-affiliated hospitals. Patients:Eighty-six severely brain-injured patients enrolled in 13 months. Interventions:None. Measurements and Main Results:All patients with severe brain injury (Glasgow Coma Scale score <9) were studied for 8 days from admission. Ventilatory pattern, respiratory system compliance, blood gas analysis, and hemodynamic profile were recorded and entered in a stepwise regression model. Length of stay in the intensive care unit, ventilator-free days, and mortality were collected. Eighteen patients (22%) developed acute lung injury on day 2.8 ± 1. They were initially ventilated with significantly higher tidal volume per predicted body weight (9.5 ± 1 vs. 10.4 ± 1.1), respiratory rate, and minute ventilation and more often required vasoactive drugs (p < .05). In addition to a lower Pao2/Fio2 (odds ratio 0.98, 95% confidence interval 0.98–0.99), the use of high tidal volume (odds ratio 5.4, 95% confidence interval 1.54–19.24) and relatively high respiratory rate (odds ratio 1.8, 95% confidence interval 1.13–2.86) were independent predictors of acute lung injury (p < .01). After the onset of acute lung injury, patients remained ventilated with similar tidal volumes to maintain mild hypocapnia and had a longer length of stay in the intensive care unit and fewer ventilator-free days (p < .05). Conclusions:In addition to a lower Pao2/Fio2, the use of high tidal volume and high respiratory rate are independent predictors of acute lung injury in patients with severe brain injury. In this patient population, alternative ventilator strategies should be considered to protect the lung and guarantee a tight CO2 control.

Pharmacotherapy for Prevention and Treatment of Acute Respiratory Distress Syndrome: Current and Experimental Approaches

The acute respiratory distress syndrome (ARDS) arises from direct and indirect injury to the lungs and results in a life-threatening form of respiratory failure in a heterogeneous, critically ill patient population. Critical care technologies used to support patients with ARDS, including strategies for mechanical ventilation, have resulted in improved outcomes in the last decade. However, there is still a need for effective pharmacotherapies to treat ARDS, as mortality rates remain high. To date, no single pharmacotherapy has proven effective in decreasing mortality in adult patients with ARDS, although exogenous surfactant replacement has been shown to reduce mortality in the paediatric population with ARDS from direct causes. Several promising therapies are currently being investigated in preclinical and clinical trials for treatment of ARDS in its acute and subacute, exudative phases. These include exogenous surfactant therapy, β2-adrenergic receptor agonists, antioxidants, immunomodulating agents and HMG-CoA reductase inhibitors (statins). Recent research has also focused on prevention of acute lung injury and acute respiratory distress in patients at risk. Drugs such as captopril, rosiglitazone and incyclinide (COL-3), a tetracycline derivative, have shown promising results in animal models, but have not yet been tested clinically. Further research is needed to discover therapies to treat ARDS in its late, fibroproliferative phase. Given the vast number of negative clinical trials to date, it is unlikely that a single pharmacotherapy will effectively treat all patients with ARDS from differing causes. Future randomized controlled trials should target specific, more homogeneous subgroups of patients for single or combination therapy.

Ventilatory and hemodynamic management of potential organ donors: an observational survey.

Objective:To determine the current standard ventilatory and cardiovascular management in potential organ donors. Design:Prospective, multiple-center, observational survey. Setting:A total of 15 intensive care units in 13 hospitals in Piedmont, Italy. Patients:A total of 34 brain-dead patients enrolled in 6 months. Measurements and Main Results:Demographics and reasons for lung transplant exclusion were recorded. Ventilatory and hemodynamic variables were compared before and after confirmation of brain death. A total of 23 potential donors were ineligible for lung donation based on pulmonary status and age. Of the 11 eligible lung donors, only two donated the lungs because five had Pao2/Fio2 ratios of <300 and four were ineligible for logistic problems. Tidal volume was 10 ± 2 mL/kg, positive end-expiratory pressure was 3.3 ± 2.7 cm H2O, Fio2 was 50% ± 18% before brain death diagnosis, and no changes were made after brain death confirmation. In potential lung donors, apnea tests were performed with apneic oxygenation after disconnection from the ventilator in all cases; tracheal suction was performed with an open circuit in eight cases, and no recruitment maneuvers were performed. Crystalloid infusion was increased after diagnosis of brain death from 187 ± 151 to 275 ± 158 mL/hr (p < .05), and central venous pressure increased from 6 ± 3 to 7 ± 3 mm Hg (p < .05). Inotropic support was used in 24 donors (70%). Conclusions:Five of 11 potential lung donors (45%) had a Pao2/Fio2 ratio of <300, making them ineligible for lung donation. After the diagnosis of brain death, ventilatory management remained the same, no maneuvers for prevention of derecruitment of the lung were performed, and cardiovascular management was modified to optimize peripheral organ perfusion. These data represent the current standard of care for ventilatory management of potential organ donors and may be suboptimal in preserving lung function. LEARNING OBJECTIVES On completion of this article, the reader should be able to: Explain the issues related to harvesting lungs for transplantation. Describe the management of potential lung donors. Use this information in a clinical setting. All of the authors have disclosed that they have no financial relationships with or interests in any commercial companies pertaining to this educational activity. Wolters Kluwer Health has identified and resolved all faculty conflicts of interest regarding this educational activity. Visit the Critical Care Medicine Web site (www.ccmjournal.org) for information on obtaining continuing medical education credit.

A Pilot Randomized Trial Comparing Weaning From Mechanical Ventilation on Pressure Support Versus Proportional Assist Ventilation.

Objectives:Despite protocols incorporating spontaneous breathing trials, 31% of ICU patients experience difficult or prolonged weaning from mechanical ventilation. Nonfatiguing modes such as pressure support ventilation are recommended. Proportional assist ventilation provides assistance in proportion to patient effort, which may optimize weaning. However, it is not known how proportional assist ventilation performs relative to pressure support ventilation over a prolonged period in the complex ICU setting. The purpose of this study was to compare the physiologic and clinical performance (failure rate), safety, and feasibility of protocols using daily spontaneous breathing trial plus pressure support ventilation versus proportional assist ventilation until ventilation discontinuation. Design:Single-center, unblinded pilot randomized controlled trial. Setting:Medical-surgical ICU of a tertiary-care hospital. Patients:Adult patients intubated greater than 36 hours were randomized if they met eligibility criteria for partial ventilatory support, tolerated pressure support ventilation greater than or equal to 30 minutes, and either failed or did not meet criteria for a spontaneous breathing trial. Interventions:Patients were randomized to the pressure support ventilation or proportional assist ventilation protocol (PAV+, Puritan Bennett 840; Covidien, Boulder, CO). Both protocols used progressive decreases in level of assistance as tolerated, coupled with daily assessment for spontaneous breathing trials. Measurements and Main Results:Of 54 patients randomized, outcome data are available for 50 patients; 27 were randomized to receive proportional assist ventilation and 23 to receive pressure support ventilation. There were no adverse events linked to the study interventions, and protocol violations were infrequent. Recruitment was slower than projected (1.3 patients per month). The median (interquartile range) time from randomization to successful extubation was 3.9 days (2.8–8.4 d) on proportional assist ventilation versus 4.9 days (2.9–26.3 d) on pressure support ventilation (p = 0.39). Time to live ICU discharge was 7.3 days (5.2–11.4 d) on proportional assist ventilation versus 12.4 days (7.5–30.8 d) on pressure support ventilation (p = 0.03). Conclusion:This pilot study demonstrates the utility, safety, and feasibility of the weaning protocols and provides important information to guide the design of a future randomized controlled trial comparing weaning from mechanical ventilation on pressure support ventilation versus proportional assist ventilation.

Cholesterol-mediated surfactant dysfunction is mitigated by surfactant protein A.

The ability of pulmonary surfactant to reduce surface tension at the alveolar surface is impaired in various lung diseases. Recent animal studies indicate that elevated levels of cholesterol within surfactant may contribute to its inhibition. It was hypothesized that elevated cholesterol levels within surfactant inhibit human surfactant biophysical function and that these effects can be reversed by surfactant protein A (SP-A). The initial experiment examined the function of surfactant from mechanically ventilated trauma patients in the presence and absence of a cholesterol sequestering agent, methyl-β-cyclodextrin. The results demonstrated improved surface activity when cholesterol was sequestered in vitro using a captive bubble surfactometer (CBS). These results were explored further by reconstitution of surfactant with various concentrations of cholesterol with and without SP-A, and testing of the functionality of these samples in vitro with the CBS and in vivo using surfactant depleted rats. Overall, the results consistently demonstrated that surfactant function was inhibited by levels of cholesterol of 10% (w/w phospholipid) but this inhibition was mitigated by the presence of SP-A. It is concluded that cholesterol-induced surfactant inhibition can actively contribute to physiological impairment of the lungs in mechanically ventilated patients and that SP-A levels may be important to maintain surfactant function in the presence of high cholesterol within surfactant.