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Predictors of Outcome for Patients With COPD Requiring Invasive Mechanical Ventilation^*

^* From the Pulmonary and Critical Care Division, New England Medical Center, Tufts University School of Medicine, Boston, MA.

Correspondence to: Scott K. Epstein, MD, FCCP, New England Medical Center, Box 369, 750 Washington St, Boston, MA 02111; e-mail: SEpstein{at}lifespan.org

	Abstract

TOP Abstract Introduction Materials and Methods Results Discussion References

 
Introduction: Accurate outcomes data and predictors of outcomes are fundamental to the effective care of patients with COPD and in guiding them and their families through end-of-life decisions.

Design: We conducted a retrospective cohort study of 166 patients using prospectively gathered data in patients with COPD who required mechanical ventilation for acute respiratory failure of diverse etiologies.

Results: The in-hospital mortality rate for the entire cohort was 28% but fell to 12% for patients with a COPD exacerbation and without a comorbid illness. Univariate analysis showed a higher mortality rate among those patients who required > 72 h of mechanical ventilation (37% vs 16%; p < 0.01), those without previous episodes of mechanical ventilation (33% vs 11%; p < 0.01), and those with a failed extubation attempt (36% vs 7%; p = 0.0001). With multiple logistical regression, higher acute physiology score measured 6 h after the onset of mechanical ventilation, presence of malignancy, presence of APACHE (acute physiology and chronic health evaluation) II-associated comorbidity, and the need for mechanical ventilation 72 h were independent predictors of poor outcome.

Conclusions: We conclude that among variables available within the first 6 h of mechanical ventilation, the presence of comorbidity and a measure of the severity of the acute illness are predictors of in-hospital mortality among patients with COPD and acute respiratory failure. The occurrence of extubation failure or the need for mechanical ventilation beyond 72 h also portends a worse prognosis.

Key Words: COPD • extubation • mechanical ventilation • outcomes analysis • weaning

	Introduction

TOP Abstract Introduction Materials and Methods Results Discussion References

 
The course of COPD is marked by progressive deterioration in lung function and functional status punctuated by episodes of acute decompensation. Hospitalization for patients with acute exacerbations carries an associated in-hospital mortality of 6 to 26%,^{1 2 3 4 5 6 7 8 9} which increases to as high as 82% if ventilatory support is required.^{1 3 4 6 7 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27} Concern about high mortality rates, the potential for weaning failure, and prolonged mechanical ventilation (MV) has led authors to seek possible predictors of outcome that may aid physicians and patients with decisions regarding the institution of invasive MV. Likewise, it becomes important to know the expected mortality rates for patients treated with conventional therapies to serve for comparison as newer modalities for treating patients with COPD and acute respiratory failure are developed (ie, noninvasive positive-pressure ventilation). Variables that may have prognostic value include the severity of underlying lung disease or chronic illness, the severity of acute illness, age, nutritional status, and the level of function before the acute decompensation. Where many studies^{1 2 9 11 14 16 18 19 22 28 29 30} appear to be contradictory in their findings, others^{4 13} have simply failed to identify any variables available at the time of hospital admission that predict outcomes in this population. The need for accurate outcomes data and predictors of outcome was well demonstrated in an analysis by Pearlman,³¹ who evaluated physicians’ prognostications regarding patients with COPD and what factors were likely to affect a patient’s outcome from an episode of MV. Physicians’ estimates varied without being well understood and appeared to be influenced more by social data than by physiologic data.

We conducted a retrospective cohort study using prospectively gathered data in patients with COPD who required MV for acute respiratory failure of various etiologies. We consolidated the prognostic variables identified by previous authors with additional variables, including the duration of MV, the presence of comorbidity, and the occurrence of extubation failure to study their interactions and to identify predictors of outcome.

	Materials and Methods

TOP Abstract Introduction Materials and Methods Results Discussion References

 
Study Population
Patients with a history of COPD requiring MV who were admitted to the medical ICU service at New England Medical Center during a 4-year period were eligible for participation in this study. The diagnosis of COPD was determined by premorbid pulmonary function testing when available (76 of 166 patients; 56 of 166 patients within 2 years of hospital admission). In the absence of documented airflow obstruction, we used clinical criteria, clinical history with compatible physical findings, and/or evidence of hyperinflation on chest radiograph, interpreted by attending pulmonary physicians, in support of the diagnosis of COPD, as described in the 1987 statement from the American Thoracic Society.³² Criteria for intubation were not standardized, and noninvasive ventilation was infrequently utilized at our hospital during the period of study. Patients were excluded from the study if they had an existing tracheotomy or required long-term ventilatory support. Patients were eligible for only a single enrollment in this study. Hospital admissions subsequent to the index admission were not considered in the primary analysis. This study includes data from 90 patient episodes that were previously reported as part of a different series.³³

Data Collection
Data were collected prospectively on all patients requiring MV. Comorbid conditions recorded were those used in the APACHE (acute physiology and chronic health evaluation) II scoring system (immunosuppression, cirrhosis, congestive heart failure [CHF], and chronic renal failure), excluding the respiratory conditions, as well as active malignancy. Recorded information about outpatient medical therapy included home oxygen, theophylline, and long-term oral and inhaled steroids. Patients were said to be receiving long-term oral steroids if they remained on a dose of prednisone 10 mg/d during the month before hospital admission. Active smoking status was defined as having smoked within the last 12 months. The occurrence of previous MV unrelated to surgery was recorded. Other data recorded included the following: pulmonary function test (PFT) results when available within 2 years of hospital admission; hematocrit, WBC count, and serum albumin, phosphorus, magnesium, and bicarbonate levels from time of hospital admission; and arterial blood gas (ABG) specimens from immediately before intubation and at the onset of weaning from MV. The etiologies of acute respiratory failure were classified into the following categories: pulmonary (eg, pneumonia, COPD exacerbation, ARDS, etc), cardiac (CHF, myocardial infarction, cardiac arrest, etc), other (upper-GI bleed, sepsis, cerebrovascular event, etc), or combinations thereof.³³ An exacerbation of COPD was defined as an increase in dyspnea with or without cough and sputum production without concomitant evidence of pneumonia (fever, leukocytosis, purulent sputum, and new infiltrates observed on chest radiography), CHF (diffuse pulmonary infiltrates, elevated jugular venous pressure or elevated pulmonary capillary wedge pressure if a pulmonary artery catheter was in place, and a third heart sound), or other definable process (eg, ARDS, pulmonary embolus, etc). Severity of illness was measured using an acute physiology score (APS) and an APACHE II score measured 6 h after intubation.³⁴

Variables obtained during the hospitalization included ventilator settings 6 h after the initiation of MV, at initiation of weaning from MV, and immediately before an extubation attempt. Respiratory mechanics (tidal volume [VT, vital capacity, and the frequency [f]/VT ratio) were measured at the discretion of the ICU team and were recorded at the onset of weaning from MV and before the spontaneous breathing trial that led to an extubation attempt. The technique used for measuring the f/VT ratio was as described by Yang and Tobin.³⁵ The duration of weaning was defined as the total duration of MV that occurred after the first weaning trial. The weaning process was not standardized but was supervised by board-certified pulmonary and critical care physicians. In general, weaning occurred by reduction in intermittent MV and pressure-support ventilation only after the patient demonstrated substantial recovery from the process that led to acute respiratory failure, hemodynamic stability, and improvement in oxygenation. Extubation was performed if the patient tolerated a minimum of 30 to 120 min on minimal ventilatory support (ie, intermittent MV = 0, pressure-support ventilation 10 cm H₂O). Patients who required reintubation or died within 72 h of extubation were classified as having extubation failure. Patients were treated routinely with nebulized bronchodilators before intubation and with bronchodilators via metered-dose inhaler with a spacer device or via nebulizer while receiving MV.

Primary outcome variables included hospital death and place of discharge. A chronic care facility (CCF) was defined as a long-term acute-care or rehabilitation facility or nursing home. Secondary outcomes included death while receiving MV, duration of weaning, need for tracheotomy, and disposition at time of discharge (eg, spontaneous ventilation, MV).

Data Analysis
A retrospective analysis was conducted on all patients with a history of COPD to identify the patient characteristics available at the time of hospital admission that predicted a poor outcome from an episode of acute respiratory failure requiring MV. Subsequent analysis was performed to identify characteristics of the hospitalization (eg, duration of MV, extubation failure) that also portended a poor outcome. A ² test was used to analyze dichotomous variables, and a Student’s t test was used for continuous variables. Nonparametric analysis using the Mann-Whitney U test was used for data with nonnormal distributions. Logistical regression models were constructed to perform multivariate analyses. The independent variables used were those variables found to have p 0.10 in univariate analysis and those variables found to be significant by previous authors. Hematocrit was excluded in the multivariate analysis, as it was accounted for in the acute physiology portion of the APACHE II score. Hospital mortality and discharge home were used as the dependent variables in separate analyses. All statistics were done using software (SPSS Advanced Statistics v6.1; SPSS; Chicago, IL).

	Results

TOP Abstract Introduction Materials and Methods Results Discussion References

 
Analysis of the Entire Cohort
One hundred sixty-six patients with COPD requiring MV were admitted to the medical ICU. Eighty-one percent of the patients were admitted from home, 13% were transferred from a CCF, and 1% were transferred from an acute-care hospital. The majority of the population was male, and more than one half had either an APACHE II-defined comorbidity or active malignancy. One third of patients were actively smoking, and one fourth had previously required MV not related to surgery. Seventeen percent of patients were receiving home oxygen therapy (Table 1 ). ABG tests were performed immediately before intubation in 108 patients, a large majority of whom were breathing supplemental oxygen, and demonstrated severe hypercapnic respiratory failure, with a pH of 7.26 ± 0.12, a PaCO₂ of 69 ± 28 mm Hg, and a PaO₂ of 88 ± 62 mm Hg (mean ± SD). The most common causes for acute respiratory failure necessitating MV are shown in Figure 1 . Thirty-eight percent of the patients were intubated in the emergency department, 15% in a ward, and 44% in the ICU. Only two patients (1%) underwent a trial of noninvasive ventilation before intubation. The mean time from hospital admission to intubation was 3 ± 6 days, with 50% intubated on the day of hospital admission. The mean APACHE II score, calculated at 6 h after the onset of MV, was 15 ± 6.

View larger version (13K): [in this window] [in a new window] [Download PPT slide]   Figure 1. Most common etiologies of respiratory failure. Some patients may have more than one precipitating cause of respiratory failure. MI = myocardial infarction.

View larger version (26K): [in this window] [in a new window] [Download PPT slide]   Figure 2. Disposition of patients at time of discharge from the hospital.

Subgroup Analysis of a Cohort With Premorbid PFTs
A subgroup of 56 patients (34%) had PFTs performed within 2 years of their intubation, and subsequent analysis will be limited to this group. The mortality rates were not significantly different for patients with PFTs performed within 2 years of intubation when compared to those without (25% vs 29%; p = 0.58). Fourteen patients had an FEV₁ that was < 30% of predicted. There was no difference in mortality (25% vs 23%; p = 0.89) or need for transfer to a CCF or rehabilitation facility (42% vs 28%; p = 0.37), when this group was compared to those patients with less severe obstruction.

Subgroup Analysis of Patients With an Exacerbation of COPD
A subgroup analysis was undertaken to evaluate the 39 patients whose cause of respiratory failure was secondary to an exacerbation of COPD. These patients were of similar ages and gender as compared to those patients intubated for other reasons. They were more likely to be receiving theophylline and inhaled steroids, and had worse lung function as measured by FEV₁ (Table 1) . Patients with an exacerbation of COPD were less ill, as measured by the APS at 6 h after intubation, and less likely to have comorbid illnesses. Preintubation ABG samples obtained in 24 patients (62%) intubated for an exacerbation of COPD demonstrated a mean pH of 7.23 ± 0.1 and a mean PaCO₂ of 78 ± 20 mm Hg.

The overall in-hospital mortality of this cohort was 15%, with 27% of the survivors requiring transfer to a rehabilitation facility/CCF (Fig 3 ). Patients with COPD exacerbations and without an APACHE II comorbidity or malignancy had a mortality rate of only 12%, which was significantly better than the 41% seen in the group intubated for other reasons with comorbidities (p = 0.0008). Twenty patients (51%) required < 72 h of MV, while 19 patients (49%) required > 72 h of MV. Patients in these groups were similar with regard to, age, gender, premorbid PFT results, presence of comorbid conditions, preintubation ABG values, and APSs measured at 6 h after intubation. Among the patients intubated for < 72 h, only one patient (5%) died and no patients required transfer to a rehabilitation facility/CCF, compared to five deaths (26%) and nine transfers (64%) in those intubated for > 72 h. Patients still intubated after 72 h required an additional 8 ± 12 days (median, 5 days; interquartiles, 1, 10) of MV.

View larger version (37K): [in this window] [in a new window] [Download PPT slide]   Figure 3. Disposition of the COPD exacerbation cohort at time of discharge from the hospital.

	Discussion

TOP Abstract Introduction Materials and Methods Results Discussion References

Previous reports^{9 10 14 24 28 40} demonstrate an inconsistent correlation between severity of acute illness scores (eg, APACHE II, simplified acute physiology score) and short-term outcome in patients with chronic respiratory insufficiency. Our finding that APS and APACHE II scores correlate with mortality supports its use in the COPD population as a marker of severity of illness. It should be emphasized that we used an APACHE II score measured at 6 h after the onset of MV, which may underestimate severity of illness.³⁴ Although many studies^{1 8 9 18 19 38} have demonstrated age to be correlated with mortality among patients receiving MV, our findings support a recent study published by Ely et al²⁹ that found age was not an independent predictor of outcome. Few authors have assessed the independent influence of underlying comorbid conditions on the outcome of patients with COPD and acute respiratory failure.^{13 18 30} Fuso et al,¹ using multivariate analysis, demonstrated that the presence of ventricular and atrial arrhythmias on hospital admission ECGs were independent predictors of short-term outcome in a cohort of patients with acute exacerbations of COPD, but only 22% of patients in that study required MV. Seneff and colleagues¹⁷ assessed the individual components of the APACHE III scoring system but did not find the presence of comorbidities to be a significant determinant of in-hospital mortality after controlling for the APS and other prognostic factors. The relatively low prevalence of individual comorbidities in our cohort limits our ability to assess their individual contributions to determining outcome, but we have demonstrated their collective negative impact on short-term survival. More importantly, in the absence of an APACHE II-related comorbidity or active malignancy, the mortality rate fell to just 16%. The finding that anemia³⁸ and hypoalbuminemia^{9 14 16 28} are predictive of short-term outcomes also supports the idea that the severity of underlying disease is an important determinate of outcome in this population.

Clinicians and patients may struggle with the decision to initiate invasive MV in patients with severe COPD for fear of the need for prolonged ventilatory support.^{4 6 9 11 13 14 16 41} The mean FEV₁ of our cohort (1.24 L; 48% predicted), although indicative of severe disease, was somewhat higher than those previously reported.^{3 4 5 6 9 11 13 14 16 41} Given the known yearly decrement in FEV₁ in patients with COPD, we likely underestimated the severity of obstruction in our patients.⁴⁷ Although PFTs aid in determining long-term prognosis,^{47 48} our data suggest that the severity of underlying lung disease is not a significant determinant of short-term outcomes in patients with COPD and acute respiratory failure. Patients with an FEV₁ < 30% predicted had survival rates similar to those with less severe disease. Interestingly, we also found a trend in those patients with a history of previous episodes of acute respiratory failure requiring MV had improved survival rates. This is in agreement with Shachor et al,⁴² who followed up patients after their first episode of acute respiratory failure requiring MV and found that short-term survival rates improved with successive episodes of MV. It appears that patients who have survived previous episodes of MV have demonstrated a survival advantage, and this information may be helpful when counseling patients.

Studies^{18 19} of heterogeneous populations requiring MV have shown outcomes that vary depending on the etiology of respiratory failure. Authors have demonstrated contrasting findings when studying COPD populations exclusively.^{4 40} The absence of pulmonary infiltrates on the hospital admission chest radiograph,^{11 13 38 43} the presence of CHF,⁹ or acute respiratory failure precipitated by an infectious etiology⁷ have all been associated with improved outcome. Our univariate analysis showed improved survival among patients with an exacerbation of COPD when compared to patients intubated for other reasons, but it was not an independent predictor in a logistic regression model.

There is a clear decision point for clinicians at the time of initiation of MV. For reasons of resource utilization and patient counseling, it makes sense to identify variables that may help guide decision making at that point. We have now identified a second decision point at 72 h after the onset of MV. Although there was no difference between the groups of patients who required > 72 h or < 72 h of MV with regard to any of the variables we found to predict outcome, the patients intubated for > 72 h had significantly higher in-hospital mortality rates (37% vs 16%, respectively) and, among survivors, a greater need for transfer to a CCF (55% vs 20%, respectively). The negative impact of an increased duration of invasive MV may help explain the benefits seen with the use of noninvasive MV to allow for early extubation in patients with COPD.⁴¹ We also confirmed that patients in whom a planned extubation attempt failed had higher mortality rates, longer duration of MV, longer ICU and hospital lengths of stay, and need for transfer to a CCF. The duration of MV remained an independent predictor of in-hospital mortality when controlling for the effect of failed extubation.

Some clinicians may find survival free of MV, rather than survival alone, to be the most suitable end point. Of the 120 survivors, only seven patients (5.8%) still required MV at the time of transfer to a CCF. No patient was discharged directly home while receiving MV. Therefore, in our cohort, "survival" was essentially synonymous with "survival free of MV" because 94% of survivors were successfully liberated from MV. No significant change in our findings is present when one reanalyzes our data, combining the seven survivors receiving MV with the nonsurviving patients requiring prolonged MV.

Our study has several weaknesses, but we do not feel they limit the significance of the findings. Only one half of our patients had PFTs performed before hospital admission. Depending on clinical criteria to diagnose COPD may have lead to inclusion of patients in the study without chronic airflow obstruction. Despite the use of prospectively gathered data, the retrospective study design precluded complete data collection on all patients (eg, albumin, phosphorus). Similarly, we were unable to assess other factors previously shown to influence mortality, such as functional status,^{9 16 17} body mass index,⁹ and the presence of cor pulmonale.^{4 9 15 16 17 44} Patients enrolled in other studies who required invasive MV through an endotracheal tube only after failing a trial of noninvasive MV may represent a selected, more ill population.^{1 4} Noninvasive positive-pressure ventilation was not yet a part of routine practice in our hospital during the period of study, and our cohort was therefore not systematically exposed to this selection process. The preintubation levels of PaO₂ were somewhat higher than those found by other authors, raising the possibility that supplemental oxygen use contributed to hypercarbia and the decision to intubate. These patients would be expected to respond quickly to therapy and may have contributed to a relatively low in-hospital mortality rate. We did not, however, find a significant difference with regard to preintubation oxygen levels when looking at groups with different survival outcomes or need for prolonged MV (< 72 h or 72 h).

The goal of this study and others has been to identify the important coexisting factors that help determine short-term outcomes in patients with COPD. A more focused understanding of the disease will allow for better utilization of medical resources and counseling of patients and their families regarding end-of-life decisions. The findings that the severity of acute illness and the presence of comorbid illness correlate with short-term mortality emphasizes the necessity of controlling for these factors in studies of future therapeutic interventions, such as ongoing investigations in the use of noninvasive positive-pressure ventilation. This study demonstrates a relatively high survival rate among patients with COPD who require invasive MV for acute respiratory failure, especially when controlling for comorbid illness. The early reversal of acute respiratory failure is associated with survival rates approaching 90%, while patients requiring prolonged MV have a poorer prognosis.

	Footnotes

 
Abbreviations: ABG = arterial blood gas; APACHE = acute physiology and chronic health evaluation; APS = acute physiology score; CCF = chronic care facility; CHF = congestive heart failure; CI = confidence interval; f = respiratory frequency; MV = mechanical ventilation; OR = odds ratio; PFT = pulmonary function test; VT = tidal volume

Received for publication January 18, 2000. Accepted for publication November 3, 2000.

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