Abstract
Objective: To assess survival and functional outcome in patients endotracheally intubated after ischemic stroke (IS) or spontaneous intracerebral hemorrhage (ICH).
Background: Endotracheal intubation is both a necessary life support intervention and a measure of severity in IS or ICH. Knowledge of associated clinical variables may improve the estimation of early prognosis and guide management in these patients.
Methods: We reviewed 131 charts of patients with IS or ICH who were admitted to the Neurosciences Intensive Care Unit at Duke University Medical Center between July 1994 and June 1997 and required endotracheal intubation. Stroke risk factors, stroke type (IS or ICH) and location (hemispheric, brainstem, or cerebellum), circumstances surrounding intubation, neurologic assessment (Glasgow Coma Score [GCS] and brainstem reflexes), comorbidities, and disposition at discharge were documented. Survivors were interviewed for Barthel Index (BI) scores.
Results: Survival was 51% at 30 days and 39% overall. Variables that significantly correlated with 30-day survival in multivariate analysis included GCS at intubation (p = 0.03) and absent pupillary light response (p = 0.008). Increase in the GCS also correlated with improved functional outcome measured by the BI (p = 0.0003). In patients with IS, age and GCS at intubation predicted survival, and in patients with ICH, absent pupillary light response predicted survival.
Conclusions: Predictors for mortality differ between patients with IS and ICH; however, decreased level of consciousness is the most important determinant of increased mortality and poor functional outcome. Absent pupillary light responses also correspond with a poor prognosis for survival, but further validation of this finding is needed.
Patients with stroke require endotracheal intubation because of a decreased level of consciousness, airway compromise, hypoxia, or apnea, or for initiation of therapeutic hyperventilation. Advanced life support including endotracheal intubation is often required in the setting of severe neurologic compromise, whether the etiology of the stroke is ischemic (ischemic stroke [IS]) or hemorrhagic (intracerebral hemorrhage [ICH]). Because stroke outcome is strongly correlated with the severity of the neurologic deficit, we expect the need for endotracheal intubation to be associated with a poor outcome. The prognosis of patients requiring endotracheal intubation and mechanical ventilation for IS or ICH is reported to be poor, with a mortality rate of 51% to 93%.1-10 Endotracheal intubation may not always be warranted because of the high mortality rate and very poor outcome.5 However, endotracheal intubation is an emergent life-supportive measure, and it is difficult to predict which patients will have meaningful neurologic recovery.
Clinical factors predicting survival and the likelihood of meaningful outcome are extremely important, and may influence management decisions. For certain subtypes of strokes, predictors of early survival have been established.11-13 The most important predictor is reduced level of consciousness as measured by the Glasgow Coma Score (GCS).1,7,10,14-18 Prior studies1,7,8,10 have reported predictors of survival in intubated patients with stroke, but to our knowledge, no study has correlated predictors of survival with functional outcome in intubated patients with stroke, as measured by independence with activities of daily living (ADLs). The purpose of this study was to identify factors influencing survival and outcome in intubated patients with stroke. These data may improve the accuracy of early prognostic estimates and therefore guide patient management and end-of-life decisions.
Methods.
We reviewed the hospital charts of all patients with IS or ICH who required endotracheal intubation admitted to the Neurosciences Intensive Care Unit (NICU) at Duke University Medical Center (DUMC; a tertiary care academic medical center) between July 1, 1994 and June 30, 1997. Institutional Review Board approval was granted to perform telephone interviews with survivors or family members of survivors.
The criteria for intubation in the NICU at DUMC include any of the following: 1) decreased level of consciousness (GCS < 10); 2) hyperventilation to decrease intracranial pressure (ICP); 3) airway protection due to absent or reduced gag reflex, airway obstruction, recurrent aspiration, or seizures lasting longer than 5 minutes; 4) hypoventilation or apnea, designated by Pco2 greater than 50 mm Hg, or decreased or ineffective respiratory effort; and 5) hypoxemia, designated by Po2 less than 60 mm Hg, Pao2/Fio2 less than 200, and evidence of infiltrate on chest radiography. All patients who were endotracheally intubated also received mechanical ventilation, and were weaned to pressure support if breathing spontaneously. The exceptions to this rule were patients who were hyperventilated for treatment of elevated ICP.
Patients were also included in the analysis if they were intubated for emergent surgery but were not extubated immediately after the procedure because of inability to protect their airways. Those patients intubated for general anesthesia before surgery and extubated immediately after surgery were excluded because the level of consciousness in these patients was adequate to allow airway protection. Patients with subarachnoid hemorrhage, hematoma secondary to arteriovenous malformation, glioblastoma multiforme, or other neoplasms were excluded, as were patients with bleeding or infarcts secondary to surgical complications, such as ventriculoperitoneal shunts, aneurysm clipping, or maxillary artery embolization.
The patient’s age, race, sex, type of stroke, time from stroke to intubation, reason for intubation, duration of survival, the underlying cause of death (if known), tracheostomy placement, comorbidities (e.g., diabetes, cancer, renal failure) and complications during the hospitalization (e.g., pneumonia, sepsis, gastrointestinal bleeding, myocardial infarction, arrhythmia), discharge destination, withdrawal of support, and stroke risk factors (i.e., diabetes, hypertension, atrial fibrillation, tobacco use, prior stroke, family history) were determined by review of medical records. GCS at initial evaluation and at intubation, assessment of brainstem reflexes, hypotension (mean arterial pressure [MAP] < 60 mm Hg), hyperglycemia (blood glucose > 200 mg/dL), hypoxia (Po2 < 60 mm Hg), intracranial hypertension (intracranial pressure or ICP > 25 mm Hg), or cerebral hypoperfusion (cerebral perfusion pressure [CPP] < 60 mm Hg, where CPP = MAP − ICP) in those with ICP monitors were also documented. Stroke type was verified by reviewing the CT scans at admission or the CT report if the scan was not available. The presence or absence of intraventricular hemorrhage was also noted.
Patients who survived and were discharged from the hospital were contacted by phone at least 6 months after their strokes. Modified Rankin Scale19 and Barthel Index (BI)20 scores were estimated from the telephone interview. The interviewer also asked the patient or family member, “If faced with the decision to intubate again, would you repeat the procedure with the knowledge of the outcome from the first stroke?”
Statistical analysis was performed using SAS for Windows (version 6.12; SAS Institute, Cary, NC). All variables were designated categorical with the exception of survival time and age, which were analyzed as continuous variables. Chi-square analysis was used for the categorical variables. Two major outcomes were analyzed.
Mortality.
Because most deaths occurred within 2 to 3 weeks after the stroke, we chose to analyze survival at 30 days as a dichotomous variable with logistic regression. Twenty-one candidate variables were tested as potential predictors. The independent contributions of variables statistically significant (p < 0.05) based on the univariate tests were then tested in a multivariable model. Kaplan-Meier survival curves were calculated for the variables significantly related to survival time (pupillary light response and GCS at intubation). Patients who were still alive at the time of follow-up were considered censored beyond that time.
Functional outcome.
Independence with ADLs was measured using the BI. For the purposes of analysis, the BI was considered as a dichotomous variable. Patients with a BI of 60 or more were designated good outcome survivors, and patients with a BI of less than 60 were designated poor outcome survivors. Analysis was performed using logistic regression.
Results.
Of 224 patients admitted to the NICU at DUMC during the study period, 131 met the inclusion criteria for endotracheal intubation for treatment of acute stroke. Forty-one patients (31%) had IS, of whom 8 had hemorrhagic transformation, and 90 patients (69%) had spontaneous ICH. Figure 1 summarizes the discharge disposition and mortality data. Table 1 gives the characteristics of the study population. The median survival for all intubated patients with stroke in this study was 34 days. The survival rate at 30 days was 51%, and the overall survival rate at follow-up was 39%. There were 51 survivors, 4 of whom were lost to follow-up, and 2 of whom refused to be interviewed. Therefore, 45 patients were included in the survivor analysis of BI, Modified Rankin Score, and the decision to repeat intubation. The follow-up time ranged from 6.1 to 44.5 months. For all survivors, the median BI was 85 and the median Modified Rankin Score was 3.
Figure 1. Flow diagram of patients admitted to the Neurosciences Intensive Care Unit (NICU), those who were intubated, and the disposition of the survivors. There was a total of 51 survivors, 6 of whom were lost to follow-up.
Characteristics of patients intubated for acute stroke
The most common cause of death was related to the acute stroke, accounting for 81% (n = 65) of deaths; 4% (n = 3) of patients died from pneumonia and sepsis as later complications of their strokes. Cardiac arrest secondary to ventricular arrhythmia, respiratory arrest secondary to airway obstruction, pneumonia, and congestive heart failure accounted for 6% (n = 5) of deaths. In 10% (n = 8) of patients, the cause of death was unknown. These patients died well after discharge from the hospital and their records were not available.
The reason for intubation was reduced level of consciousness in 84.0% of patients in the study, hypercarbia/apnea in 6.1%, hypoxia in 4.6%, bulbar dysfunction in 2.3%, hyperventilation in 1.5%, status epilepticus in 0.8%, and surgery in 0.8%. Several patients had more than one reason for intubation, but the most urgent indication was documented for the purposes of analysis. Reason for intubation in these patients was not a significant predictor of survival.
The duration of intubation was measured at three end points: the time of extubation, death, or removal of the tracheostomy. The latter measurement was an estimate because some patients had the tracheostomy removed during the follow-up time, and the families were unsure of the time of removal. Also, patients who still had a tracheostomy at follow-up were assigned a duration time from intubation to the follow-up interview. The median duration of intubation was 5 days, with a range of 1 to 844 days. Thirty-three (25%) of the intubated patients had tracheostomies placed, and their 30-day survival rate was 41.8%. For patients who did not have tracheostomies, the 30-day survival rate was 58%. In the nonsurvivor group, 7.8% had tracheostomies performed, and 92% did not. The median time from stroke to intubation was less than 1 day (range, 0 to 13 days), and survival appeared to correspond with a longer time until intubation (p = 0.04).
The most common stroke risk factor was hypertension (79.4%), followed by tobacco use (34%), prior stroke (29%), diabetes (25%), and atrial fibrillation (18%). A ventriculostomy was done in 45% of intubated patients with stroke (10% for IS and 90% for ICH). Of those patients with ICP monitoring, 51% had an ICP greater than 25 or a CPP less than 60. Anticoagulation was administered to 31% of patients, including those who were admitted on warfarin and those placed on heparin. During the hospitalization for acute stroke, 21% of patients were hypotensive (MAP < 60), 24% were hypoxic (Po2 < 60), 47% were hyperglycemic (blood glucose > 200), and 14% had a seizure.
As a measure of functional outcome, 22 of 28 (78.6%) patients discharged to rehabilitation facilities had a BI of at least 60, compared with 5 of 11 (45.4%) patients discharged to nursing homes, and only 1 of 5 (20%) patients discharged for palliative care. The number of patients discharged to rehabilitation with a BI of at least 60 was significantly greater compared with the other two groups (p = 0.006).
Treatment withdrawal was designated as either extubation or removal from the ventilator with a T-piece. Of 44 patients who had treatment withdrawn, the 30-day survival rate was 16%. For the 87 patients who did not have treatment withdrawn, the 30-day survival rate was 69%. After their strokes, 49% of patients were declared “Do Not Resuscitate.” At the follow-up interview, the survivors or their family members were asked if they would agree to reintubation if necessary, and 24 (53%) answered “yes,” 12 (27%) answered “no,” and 9 (20%) were undecided.
Table 2 gives the univariate predictors for survival at 30 days. This outcome measure was chosen because most deaths occurred in the first 2 to 3 weeks. Independent variables that persisted as significant predictors of 30-day survival in the multiple logistic regression model were GCS at intubation (p = 0.03, odds ratio [OR] = 0.849, and c index = 0.805) and bilateral absent pupillary light reflex (p = 0.008, OR = 5.3, c index = 0.805). Analysis by logistic regression showed that with increasing GCS at intubation there was a significant positive correlation with independence with ADLs, as measured by the BI (p = 0.002, c index = 0.671).
Influence of clinical variables on survival in intubated patients with stroke analyzed by univariate methods
Table 3 is a summary of the median GCS at intubation, median survival in days, median BI, and the survival at 30 days according to stroke subtype. The 30-day survival rate was lowest in patients with lobar hemorrhage (27%) and highest in patients with brainstem hemorrhages (63%). The median GCS at intubation, 30-day survival rate, and BI were not significantly different among the stroke subtypes. However, when logistic regression was performed on the IS and ICH patient groups separately, the variables predicting survival were different. In patients with IS, the predictors included age (p = 0.019, OR = 1.105, c index = 0.895) and GCS at intubation (p = 0.004, OR = 0.549, c index = 0.895). In patients with ICH, absent pupillary light response predicted survival (p = 0.002, OR = 6.667, c index = 0.779). There were no statistically detectable interactions among the IS group, the ICH group, and predictors for mortality; however, group differences were apparent. The GCS was significantly higher in the IS group (median GCS = 8) compared with the ICH group (median GCS = 7) by Wilcoxon signed rank test (p = 0.0125). Also, the median age was higher in the IS group (68.9 years) compared with the ICH group (57.6 years; p = 0.049). Reactive pupils were documented in 72% of patients with ICH, compared with 92.7% of patients with IS, with a significant relationship between absent pupillary light response and ICH by chi-square analysis (p = 0.008).
Summary of 30-day survival, median survival, median Barthel Index, and Glasgow Coma Score at intubation by stroke subtype
The survival curves for intubated patients with stroke by absence or presence of pupillary light responses and GCS are shown in figures 2 and 3⇓, respectively. Table 4 is a summary of the number of intubated patients with stroke with a GCS of 3 to 5 (rank 1), 6 to 8 (rank 2), 9 to 11 (rank 3), and 12 to 15 (rank 4), with the corresponding 30-day survival, median survival, and functional outcome (median BI). Increasing GCS at intubation correlates with higher 30-day survival rate, longer survival, and better independence with ADLs in our study population.
Figure 2. Survival curves for intubated patients with stroke by pupillary response (absent versus present). Absent pupillary light response is significantly correlated with 30-day survival using the multiple logistic regression model (p = 0.008, OR = 5.3, c index = 0.805).
Figure 3. Survival curves for intubated patients with stroke by Glasgow Coma Score (GCS) rank. With increasing rank, the GCS is significantly correlated with 30-day survival using the multiple logistic regression model (p = 0.03, OR = 0.849, c index = 0.805).
Survival at 30 days, duration of survival, and Barthel Index by Glasgow Coma Score (GCS) rank for intubated patients with stroke
Sixteen patients underwent craniotomies for decompression or hematoma evacuation. Six patients had hematoma evacuations of either lobar or deep hemorrhages, four of whom survived with BIs of 50, 45, 40, and 0. Eight patients underwent suboccipital craniotomies for evacuation and decompression of cerebellar hemorrhages, five of whom survived with BIs of 0, 60, 85, 90, and 100. Of the four patients with cerebellar infarcts, two underwent posterior fossa decompression, and both survived with BIs of 40 and 90.
Discussion.
The results of this retrospective analysis agree with prior studies showing that patients with acute stroke who require intubation have a high mortality rate. The predictors of 30-day mortality in this study include GCS at intubation and absent pupillary light responses. Increase in GCS rank also correlated with improved functional outcome as measured by independence with ADLs. Survival was significantly influenced by age and GCS at intubation in patients with IS, and absent pupillary light reflexes in patients with ICH. Overall, however, age and other variables such as hypertension, hyperglycemia, or atrial fibrillation were not predictors of survival or outcome.
Prior studies of intubated patients with stroke.
Most of the previous studies of intubated patients with stroke have reported mortality rates greater than 70%.1-6 Ludwigs et al.6 reported a subgroup of 65 patients from 1976 to 1986 admitted to an ICU and intubated for cerebrovascular disease who had 75% ICU mortality and 92% in-hospital mortality rates. Burtin et al.1 reported a similar outcome for 170 patients intubated for acute IS, ICH, or subarachnoid hemorrhage, with 72% ICU mortality and 92% 1-year mortality rates. Wijdicks and Scott3,4 reported a 71% mortality rate in a series of patients intubated for hemispheric stroke,4 and an 88% mortality rate in vertebrobasilar IS.3 Steiner et al.7 reported a 52% ICU mortality rate and a 67% 1-year mortality rate in the only prospective outcome study of intubated patients with stroke. The most recent study, by Gujjar et al.,8 reported a 57% mortality rate in patients with IS and a 58% mortality rate in patients with ICH. This same study showed that the timing of intubation influenced survival in patients with ICH, with poorer survival in patients requiring intubation at presentation. In contrast, most of our patient population underwent intubation within 1 to 2 days from stroke onset, regardless of stroke type. Despite our use of a slightly higher GCS threshold for intubation than that used by Gujjar et al.,8 the mortality rates in both studies are similar. Our results, in addition to mortality data reported recently,7-10 show an improvement in survival compared with previous studies. One explanation may be that management of acute neurologic complications is improving. For example, aspiration and the presence of dysphagia are associated with increased mortality in patients with IS,21 and perhaps more patients are being intubated to prevent this complication. In addition, neurologists and intensive care physicians may be biased toward aggressively treating those patients who they believe show some promise of recovery.
Glasgow Coma Score at intubation.
Reduced level of consciousness (GCS < 10) significantly influences mortality in IS and ICH in most studies.1,7,8,10-18,22-24 The patient’s requirement for intubation and mechanical ventilation within the first day after the stroke is a valid marker for coma and therefore stroke severity.25 We used a GCS ranking system to stratify neurologic deficit with respect to level of consciousness and found that the GCS rank at the time of intubation, and not at the time of stroke, significantly predicts survival at 30 days in multivariate analysis. Neurologic deterioration resulting in a reduced level of consciousness and the need for airway protection is associated with tissue shifts secondary to edema. This was demonstrated in studies of ICP monitoring after acute hemispheric stroke, in which the development of decreased level of consciousness was not correlated with a rise in ICP, but was more closely correlated with edema and tissue shifts.26,27 In a study of patients with supratentorial hemorrhage, neurologic deterioration was correlated with the volume of the hemorrhage and subsequent edema and mass effect, but not with GCS or the severity of the neurologic deficit on admission.28 However, that study included only the patients with hemorrhages who were not comatose (GCS ≥ 8) on admission, whereas 64% of our patients (both IS and ICH) had a GCS of 8 or less at presentation.
Absent pupillary light response.
The absence of pupillary reactivity was an independent predictor of survival at 30 days in the group combining IS and ICH, as well as the ICH-alone group in our study. The presence of a pupillary abnormality has been reported to be a significant predictor of survival29 and a predictor of poor outcome30 in ICH. In a prior study, absent bilateral pupillary light reflex was a univariate but not multivariate predictor of 60-day survival in a study of intubated patients with stroke.7 Results similar to ours were obtained by Gujjar et al.,8 who reported absent pupillary responses to be a significant predictor of survival in mechanically ventilated patients with IS and ICH. Ropper and Shafran31 found that drowsiness and pupillary asymmetry were the most consistent findings associated with early brain edema after IS, and on autopsy, several patients had evidence of midbrain parenchymal distortion. They speculated that edema was causing not only oculomotor nerve compression but direct midbrain compression, to account for the pupillary asymmetries and drowsiness. One could also speculate that, in severe IS or ICH, the pupillary abnormalities are due to a central herniation syndrome, especially in those patients who progress to brain death. Our results are in agreement with the cited studies showing that prognosis is poor in patients with stroke who have pupillary abnormalities, but this has not been a consistent finding in all studies of patients with stroke. Perhaps signs of pupillary abnormalities are most relevant in patients with severe IS or ICH.
Stroke subtype, age, and other risk factors for mortality.
The type and location of stroke in patients requiring intubation were not significant predictors of 30-day survival or functional outcome in our study. Despite the lack of statistical significance in multivariate analysis, patients with lobar hemorrhages had the poorest survival and outcome compared with the other types of stroke. This concurs with a previous study.32 The small numbers of patients in some of the stroke subtype groups limit the analysis, and larger numbers may have shown significant differences in survival and outcome. Jorgensen et al.33 showed that in patients with severe strokes, those with ICH made up the highest proportion compared with IS. When the two types of stroke were matched by severity, however, the outcome was the same.
Gujjar et al.8 reported mortality rates that were essentially the same in patients with IS and those with ICH, but the predictors for mortality were different for the two groups. In IS, the predictors were male sex and absent pupillary reflexes, and in ICH, higher mortality was associated with older age, intubation for neurologic deterioration, intubation on presentation, and absent pupillary, corneal, and oculocephalic reflexes.8 We also found differences in predictors of mortality between patients with IS and ICH, but these differed somewhat from those reported by Gujjar et al.8 In patients with IS, the predictors were age and GCS at intubation, and the predictor in ICH was absent pupillary response. There were no statistically detectable interactions among the stroke types and the predictors. However, patients with IS tended to have a higher GCS at intubation, were older, and had a lower proportion of nonreactive pupils than patients with ICH, which may explain these results.
In prior studies of IS and ICH, age has often been a significant predictor of mortality and outcome. Several studies have shown that age greater than 65 years in patients with stroke is predictive of outcome and death after 30 days.15,17,32,34-37 In a study of intubated patients with stroke, age greater than 65 years was a significant factor in 60-day survival.7 Our results showed that age was a marginally (p = 0.019) significant predictor of survival in patients with IS, but was not a significant predictor of survival or functional outcome in the overall analysis of combined patients with IS and ICH. This is in agreement with others who asserted that the severity of the stroke appeared to outweigh the significance of increasing age.1 Similarly, severity of the stroke overshadows other established predictors of survival and outcome, such as hyperglycemia,15,34,38 atrial fibrillation,36,39 and hypertension.32
Outcome.
The results of our study show that GCS correlates not only with 30-day survival, but with functional outcome using the BI as a measure of independence with ADLs. We used a dichotomous approach to grouping patients’ outcomes based on previous reports,7,40 designating a BI of less than 60 as at least partial dependence and a BI of 60 or more as at least partial independence. The median BI score was 85 for our study population, signifying independence with ADLs. However, the effect of GCS on BI is illustrated in table 4, which shows higher median BI scores with increasing GCS at intubation. Our results suggest that if a patient with stroke requires intubation and survives the first 30 days after the stroke, the potential exists for rehabilitation and a good functional outcome if the patient’s level of consciousness was not severely impaired at the time of intubation.
There are some limitations to this study. First, it is a retrospective study over a 3-year period, and the follow-up times vary from 6 months to 3 years. We therefore focused on 30-day mortality, because most patients who died did so in the first 2 to 3 weeks.
Second, the duration of intubation in this study is more difficult to quantify after 2 weeks of intubation, because after that time most patients underwent tracheostomy. Also, the group of patients with a short duration of intubation included those who died, those who had treatment withdrawn, and those who survived, making interpretation of this variable difficult. Eight patients in our study had their tracheostomies removed, but the remaining nine survivors did not. A small study of patients with hemispheric stroke intubated secondary to neurologic deterioration indicated that intubation for less than 72 hours may be suggestive of a better outcome.2 However, in that study, only one patient had a tracheostomy, and the outcome of this patient was not evident. The prognosis of patients with stroke who require tracheostomies should be further studied.
Third, our sample size limited our ability to use a split-sample design to validate the predictive model of GCS and pupillary abnormality on survival. Also, the varying predictors of mortality between the IS and ICH groups may have been influenced by small numbers. The impact of abnormal pupillary light responses on survival in intubated patients with stroke raised in this and previous studies requires validation.
Conclusions.
Survival in patients with IS and ICH requiring intubation is poor, and our mortality data are similar to those in recent reports.7-10 We found that patients with a reduced level of consciousness at the time of intubation or absent pupillary light responses had a poor prognosis for early survival and functional outcome. The data reinforce prior work showing that reduced level of consciousness is a particularly poor prognostic factor after stroke. In addition, our results are in agreement with a recent study showing the influence of absent pupillary responses on survival in these patients, and that mortality predictors differ for patients with IS and ICH.8 Those patients surviving the early stroke period have the potential for a good functional outcome as measured by independence with ADLs. The influence of pupillary abnormalities on survival and outcome in intubated patients with stroke is a variable that needs to be validated in further studies. The information presented in this study may be useful for family discussions regarding the prognosis of patients with severe strokes, and may help to guide end-of-life decisions.
Acknowledgments
Acknowledgment
The authors thank Julie K. Farrell for her assistance with the chart review and the database, and Larry Goldstein, MD for his helpful review and comments.
- Received August 28, 1998.
- Accepted in final form September 9, 1998.
References
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