Recovery Rate and Prognosis in Older Persons Who Develop Acute Lung Injury and the Acute Respiratory Distress Syndrome

More than half of all days spent in an intensive care unit are incurred by patients older than 65 years of age, and the number of days per year spent in the intensive care unit (per 1000 person-years) is sevenfold higher for persons older than 75 years compared with persons younger than 65 years (1). The population of older persons and their respective proportion of health care expenditures are expected to double by 2030 (2), and some have suggested that we ration the care provided to older patients (3-5). Indeed, physicians in the Study to Understand Prognoses and Preferences for Outcomes and Risks of Treatments (SUPPORT) withheld mechanical ventilation at higher rates in older patients, especially in patients 70 years of age or older (6-8). However, previous reports of older patients with respiratory failure from various causes have indicated that recovery and overall prognosis in this age group do not justify using age alone to determine treatment decisions (9-11). Instead, the decision to place older persons with acute lung injury on mechanical ventilation should incorporate several factors, including comorbid illnesses (12), patient preference or previously stated wishes, physician gestalt, and bedside judgment. The incidence of acute respiratory failure requiring mechanical ventilation increases 10-fold from the ages of 55 to 85 years (13), resulting in an increasing number of elderly patients receiving treatment in intensive care units (1, 11, 14). Therefore, health care professionals need to understand the effect of age on outcomes of acute lung injury and the acute respiratory distress syndrome (henceforth called acute lung injury) to guide their treatment decisions and prognostic discussions (15, 16). In most investigations, the mortality rate from acute lung injury has ranged from 40% to 50% (15, 17-21). Data from a large cohort followed from 1983 to 1993 revealed encouraging declines in acute lung injury-related mortality but showed that these improved outcomes were confined largely to patients younger than 60 years of age (22). We used data from an acute lung injury database sponsored by the National Heart, Lung, and Blood Institute (23, 24) to investigate the effect of age on the ability to recover from acute lung injuryinformation that could prove extremely important given the growing number of older persons at risk for acute lung injury (2-5, 16, 25). We hypothesized that age would independently affect acute lung injury outcomes, even after adjustment for severity of illness and other covariates. To investigate this hypothesis, we asked the following questions about age and acute lung injury: 1) How does age affect survival from acute lung injury? 2) Do physiologic recovery and successful liberation from the ventilator take longer in older patients? Methods Patients We examined data on 902 patients who participated in the National Heart, Lung, and Blood Institute multicenter, randomized trials of the Acute Respiratory Distress Syndrome (ARDS) Network between 18 March 1996 and 28 May 1999. Patients were enrolled from 24 hospitals associated with 10 U.S. medical centers. Included in this analysis were the 861 patients from a recently reported randomized trial of mechanical ventilation that compared lower with traditional tidal volume (6 mL/kg of ideal body weight vs. 12 mL/kg of ideal body weight) (24). After the early stopping of the ventilator trial by the data safety monitoring board for efficacy, the 41 additional patients in our analysis had received lisofylline or placebo with the lower tidal-volume strategy. (Lisofylline is a xanthine derivative that decreases the inflammatory response.) The institutional review boards of each participating medical center or hospital approved this study. Patients or their surrogate provided informed consent before enrollment. The study was conducted in accordance with the established ethical standards of the medical centers and with the principles of the Declaration of Helsinki (26). We analyzed age as a binary category and according to decade. To assess the varying effect of age on outcomes, we also used age, coded as a series of indicator variables for decade of age, in multivariable analysis. In keeping with our prospectively defined analysis plan, we decided a priori to report these data as a comparison of the patients younger than 70 years of age (n = 729) with the patients 70 years of age or older (n = 173). In the absence of any clearly defined age cutoff designating patients as elderly, we chose these binary age categories on the basis of data from the SUPPORT studies suggesting that physicians most often used 70 to 75 years of age as a decision-making cut point affecting intensity of care and threshold for withholding mechanical ventilation (6-8). However, additional analyses defining older persons at lower (65 years of age) and higher (80 years of age) cutoffs have yielded similar results. Details of inclusion and exclusion criteria for the ARDS network trials have been reported previously (23, 24). Briefly, patients were eligible if they required mechanical ventilation for acute lung injury, with a partial Po 2 divided by fraction of inspired oxygen of 300 or less, bilateral pulmonary infiltrates consistent with pulmonary edema, and no clinical evidence of left atrial hypertension. If measured, the pulmonary capillary wedge pressure was required to be 18 mm Hg or less (27). The major reasons for exclusion were as follows: more than 36 hours elapsed since the inclusion criteria were met, age younger than 18 years, participation in other acute lung injury trials in the past 30 days, pregnancy, increased intracranial pressure, neuromuscular disease that could impair spontaneous breathing, sickle-cell disease, severe chronic respiratory disease (as previously described [23, 24]), massive obesity, burns covering more than 30% of body surface, comorbid conditions with an estimated 6-month mortality rate greater than 50%, bone marrow or lung transplantation, chronic liver disease (as defined by Child-Pugh Class C [28]), inability to consent, and attending physician refusal or unwillingness to commit full life support. The patient's surrogate and managing physician determined whether to withdraw mechanical ventilation, and we analyzed all patient data on an intention-to-treat basis. Protocol for Mechanical Ventilator Management Mechanical ventilation was performed in strict accordance with the ARDS network study protocol (24). Weaning was done according to a protocol that included a daily weaning screen followed by pressure support ventilation and a 2-hour spontaneous breathing trial. The Daily Weaning Screen and Spontaneous Breathing Trials Patients were followed daily to determine when they passed the following weaning screens, which were based on data from previous investigations (29-31): oxygen saturation of at least 0.88 on positive end-expiratory pressure of 8 cm H2O or less and a fraction of inspired oxygen of 0.40 or less, systolic blood pressure of 90 mm Hg or more without vasopressor support, and demonstration of spontaneous inspiratory efforts (initiating breaths above the rate of the ventilator setting). After meeting these daily weaning screen criteria, patients were given a 5-minute trial of spontaneous breathing with continuous positive airway pressure of 5 cm H2O. If the respiratory rate remained 35 breaths/min or less, the patient entered a pressure support weaning protocol and then a 2-hour spontaneous breathing trial on a T-piece or continuous positive airway pressure of 5 cm H2O without pressure support ventilation, as described previously (www.ardsnet.org). The spontaneous breathing trial was terminated if any of the following predetermined conditions were met: respiratory rate greater than 35 breaths/min for more than 5 minutes, sustained arterial oxygen saturation less than 0.90, heart rate that had increased by 20% or more compared with the rate at 0600 hours (6 a.m.), marked use of accessory respiratory muscles, abdominal paradox, marked subjective dyspnea, or diaphoresis. If any of these criteria were met, then the ventilator was set at the patient's previously used settings and the patient was weaned by using the pressure-support protocol until the following day, at which time the daily weaning screen would be performed again. Patients passed the spontaneous breathing trial if none of the above conditions were met. After passing the 2-hour spontaneous breathing trial, patients graduated to unassisted breathing, meaning that they were extubated, continued receiving a T-piece, or received continuous positive airway pressure of 5 cm water without pressure support ventilation. Definitions of Recovery Landmarks To determine the rate of recovery of older compared with younger patients, the earliest time at which patients had successfully passed four clearly defined recovery landmarks was recorded: 1) the daily weaning screen, 2) the 2-hour spontaneous breathing trial, 3) the date on which the patient began a period of unassisted breathing that lasted 48 hours or more, and 4) discharge from the intensive care unit alive and with no mechanical ventilation. Severity of Illness Classification and Organ or System Failure Baseline severity of illness was recorded at enrollment by using the Acute Physiology, Age, and Chronic Health Evaluation III (APACHE III) score (32). During analysis, we used a modified APACHE III score that excluded age so that age would remain an independent factor of outcome. Nonpulmonary organ system failures were also recorded by using definitions based on the following objective criteria (24, 33-35): for circulatory failure, a systolic blood pressure of 90 mm Hg or less or the need for treatment with any vasopressor; for coagulation failure, a platelet count of 80 109 cells/L or less; for central nervous system failure, a Glasgow coma scale rating less than 12; for hepatic failure, a serum bilirubin concentration