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Abstract

  1. Top of page
  2. Abstract
  3. Continuing Medical Education
  4. Methods
  5. Results
  6. Discussion
  7. Limitations
  8. Conclusions
  9. References

ACADEMIC EMERGENCY MEDICINE 2012; 19:133–138 © 2012 by the Society for Academic Emergency Medicine

Abstract

Objectives:  The objective was to explore the incidence, predictors, and prognostic significance of emergency department (ED) neurologic deterioration in patients with spontaneous intracerebral hemorrhage (SICH).

Methods:  This was a retrospective cohort study conducted at the ED, neurocritical care unit, and general intensive care unit of a university-affiliated medical center. Consecutive adult SICH patients treated in our ED from January 2002 through December 2009 were included, identified from the registered stroke data bank. These were cross-checked for coding with International Classification of Diseases, Ninth Revision, Clinical Modification 431 and 432.9. Enrolled patients had SICH with elapsed times of <12 hours and Glasgow Coma Scale (GCS) scores ≥ 13 on arrival. ED neurologic deterioration was defined as having a two-or-more-point decrease in consciousness noted in any GCS score assessment between ED presentation and admission. Comparisons of numerical data were performed using an unpaired t-test (parametric data) or Mann-Whitney U-test (nonparametric data). Comparisons of categorical data were done by chi-square tests. Variables with p < 0.1 in univariate analysis were further analyzed using multiple logistic regression. No variable automated or manual selection methods were used.

Results:  Among the 619 patients with SICH included in the study, 22.6% had ED neurologic deterioration. Independent predictors for ED neurologic deterioration included regular antiplatelet use, ictus to ED arrival time under 3 hours, initial body temperature ≥ 37.5°C, intraparenchymal hemorrhage associated with intraventricular hemorrhage (IVH), and presence of a midline shift of greater than 2 mm on computed tomography (CT). ED neurologic deterioration was associated with 1-week mortality, 30-day mortality, and poor neurologic outcome on discharge.

Conclusions:  Nearly one-quarter of SICH patients with an initial GCS of 13 to 15 had a two points or more deterioration of their GCS while in the ED. ED neurologic deterioration was associated with death and poor neurologic outcomes on discharge. Several risk factors that are available early in the patients’ courses appear to be associated with ED neurologic deterioration. By identifying patients at risk for early neurologic decline and intervening early, physicians may be able to improve patient outcomes.


Continuing Medical Education

  1. Top of page
  2. Abstract
  3. Continuing Medical Education
  4. Methods
  5. Results
  6. Discussion
  7. Limitations
  8. Conclusions
  9. References

Continuing Medical Education Activity in Academic Emergency Medicine

CME Editor: Hal Thomas, MD

Authors: Ju-Sing Fan, MD, Hsien-Hao Huang, MD, Yen-Chia Chen, MD, David Hung-Tsang Yen, MD, PhD, Wei-Fong Kao, MD, Mu-Shun Huang, MD, Chun-I Huang, MD, and Chen-Hsen Lee, MD

Article Title: Emergency Department Neurologic Deterioration in Patients With Spontaneous Intracerebral Hemorrhage: Incidence, Predictors, and Prognostic Significance

If you wish to receive free CME credit for this activity, please refer to the website: http://www.wileyblackwellcme.com.

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Blackwell Futura Media Services designates this journal-based CME activity for a maximum of 1 AMA PRA Category 1 Credit™. Physicians should only claim credit commensurate with the extent of their participation in the activity.

Blackwell Futura Media Services is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.

Educational Objectives

After completing this exercise the practitioner will be better able to discuss the risk of meningitis in children between 6 months and 18 months who present with a febrile seizure.

Activity Disclosures

No commercial support has been accepted related to the development or publication of this activity.

Faculty Disclosures:

CME editor – Hal Thomas, MD: No relevant financial relationships to disclose.

Authors – Linda Papa, MDCM, MSc, Ian G. Stiell, MD, MSc, Catherine M. Clement, RN, Artur Pawlowicz, Andrew Wolfram, Carolina Braga, Sameer Draviam, MD, and George A. Wells, PhD: No relevant financial relationships to disclose.

This manuscript underwent peer review in line with the standards of editorial integrity and publication ethics maintained by Academic Emergency Medicine. The peer reviewers have no relevant financial relationships. The peer review process for Academic Emergency Medicine is double-blinded. As such, the identities of the reviewers are not disclosed in line with the standard accepted practices of medical journal peer review.

Conflicts of interest have been identified and resolved in accordance with Blackwell Futura Media Services’s Policy on Activity Disclosure and Conflict of Interest. No relevant financial relationships exist for any individual in control of the content and therefore there were no conflicts to resolve.

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Spontaneous intracerebral hemorrhage (SICH) causes significant morbidity and mortality throughout the world.1 Neurologic deterioration within the first 24 to 48 hours affects approximately one-third of patients and has been previously associated with poor prognosis.2–4 Information regarding factors contributing to early neurologic deterioration can guide early management strategies and lead to more favorable outcomes.2–7 Previous studies have shown that neurologic deterioration is most likely to occur within the first few hours of care, indicating that this decline in neurologic status may occur in the emergency department (ED).2–4,7,8 However, ED neurologic deterioration was not specifically addressed in these studies. With this in mind we developed our study to accomplish several aims: 1) describe the epidemiology of patients with SICH who suffer neurologic decline in the ED, 2) describe the clinical characteristics that are most associated with ED neurologic deterioration in SICH patients, and 3) evaluate the prognostic significance of ED neurologic decline. Knowing the prevalence and which factors are associated with ED neurologic decline among patients with SICH may help emergency physicians and their consultants identify patients who are more likely to benefit from aggressive management.9–12

Methods

  1. Top of page
  2. Abstract
  3. Continuing Medical Education
  4. Methods
  5. Results
  6. Discussion
  7. Limitations
  8. Conclusions
  9. References

Study Design

This study was a retrospective analysis of prospectively registered SICH patients. The hospital’s institutional review board approved the study.

Study Setting and Population

Prospective Data Collection.  Patients were treated in the ED of Taipei Veterans General Hospital, a 2900-bed, university-affiliated medical center with an annual ED census of 86,621. Approximately 251 nontraumatic ICH patients are treated annually. Our study was a consecutive sample of all patients with SICH between January 1, 2002, and December 31, 2009. We excluded patients with spontaneous subarachnoid hemorrhage, spontaneous subdural hemorrhage, and those who were on warfarin therapy.

Patients suspected of stroke were managed using a standardized clinical protocol established in 2001 in our ED. This protocol consists of a series of standard steps and associated time goals for vital sign assessments, blood sugar, laboratory testing, brain imaging, neurospecialist consultation, and other goal-directed ED interventions like blood pressure control, fever control, etc. According to the protocol, initial vital signs and Glasgow Coma Scale (GCS) scores were checked immediately after arrival, and extensive assessments (medical history, physical and neurologic examination, laboratory studies, and imaging studies) were completed within 1 hour.

Retrospective SICH Chart Review.  Consecutive SICH patients treated in our ED from January 2002 through December 2009 were initially identified using the hospital’s stroke registry data bank. To avoid missing potential participants, charts were cross-checked for coding with International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) 431 and 432.9 (for SICH). Medical charts were comprehensively and extensively reviewed. A neuroradiologist blinded to the study purpose evaluated the computed tomography (CT) scans. Exclusion criteria included the following: less than 18 years of age; an elapsed time of more than 12 hours before arrival; initial ED GCS score less than 13; ICH secondary to trauma, brain abscess, brain tumor, brain infarct, arteriovenous malformation, or bleeding tendency; pure nonintraparenchymal hemorrhage, such as spontaneous subarachnoid hemorrhage, spontaneous subdural hemorrhage, and primary intraventricular hemorrhage (IVH); charts lacking certain important information (brain images, GCS record, 30-day and discharge status); patients on warfarin therapy; and patients transferred from other hospitals.

Study Protocol

Prospective Study.  After the diagnosis of ICH was made, the on-site nurses registered patients’ characteristics into the hospital’s stroke data bank. Variables recorded in the registry for SICH patients include onset time; initial ED GCS score; initial vital signs; times that brain CT was ordered, performed, and read; type of ICH; hematoma volume; presence or absence of subarachnoid or IVH; time and GCS score at neurologic deterioration (if present); and admission time.

Neurologic and neurosurgical consults were obtained after the diagnosis was made, and patients were then treated and closely monitored in the ED until admission. During the ED stay of SICH patients, nurses checked vital signs and GCS score every 15 minutes. A greater than 2-point decrease in the GCS score was considered a significant neurologic deterioration, in which case the emergency physician performed a reassessment. The exact times of all events and results of all assessments were recorded in the medical chart by on-site physicians and nurses. Although the primary purpose of the protocol is to improve the stroke care efficiency and quality, it enabled us to collect more standardized information about ED stroke patients, increasing the data quality of this retrospective study.

Definition of ED Neurologic Deterioration.  ED neurologic deterioration was defined as ≥2-point decrease in consciousness in the GCS score noted in any assessment between arrival in the ED and neurocritical care unit or intensive care unit admission. A GCS drop of ≥2 points due to seizure or effects of medications for seizure control was not considered ED neurologic deterioration if the GCS score recovered to baseline after the episode. Two emergency physicians independently reviewed all medical charts and determined the presence or absence of ED neurologic deterioration. The degree of agreement between the two physicians was assessed by kappa value. When there was disagreement, consensus was reached following comprehensive discussion.

Retrospective SICH Chart Review.  Variables possibly related to ED neurologic deterioration and variables needed for this study were defined before abstracting data from the data bank and medical charts. Two trained research assistants blinded to the study purpose entered the abstracted data into the new data bank used for study analyses. Patient characteristics that could be collected shortly after ED arrival were abstracted as independent variables for analysis of ED neurologic deterioration predictors, and those that could be collected soon after admission were abstracted as independent variables for determining prognostic significance of ED neurologic deterioration. The variables used for identifying ED neurologic deterioration predictors included age; sex; history of diabetes, coronary artery disease, and congestive heart failure; smoking; alcohol consumption; antiplatelet agent use; an ictus time of less than 3 hours; atrial fibrillation on electrocardiogram; QTc prolongation on electrocardiogram; initial ED systolic blood pressure (sBP), diastolic blood pressure (dBP), mean arterial pressure (MAP), and pulse pressure (PP); laboratory studies; hematoma size; infratentorial ICH; midline shift; and IVH. Data used for determining the prognostic significance of ED neurologic deterioration included the variables mentioned above and variables generated after the ED stay: maximum and minimum sBP, dBP, MAP, and PP during ED stay; greatest changes in sBP, dBP, MAP, and PP in ED; use of antihypertensive, osmotic, or antiepileptic agents; hematoma evacuation; external ventricular drainage placement; invasive intracranial pressure monitor placement; concurrent infection; concurrent congestive heart failure; total ED stay time; GCS on admission; and presence or absence of ED neurologic deterioration. A midline shift was defined as a lateral pineal shift of ≥2 mm from the falx at the level of the septum pellucidum. Good and bad neurologic outcomes were defined as modified Rankin Scale of ≤2 points and ≥5 points, respectively.

Data Analysis

Statistical analysis was performed using SPSS software (version 15.0, SPSS Inc., Chicago, IL). Statistical tests were two-sided, and the significance level was set at p < 0.05. The distribution of the data was assessed with the Kolmogorov-Smirnov test. Comparisons of numerical data were performed using an unpaired t-test (parametric data) or Mann-Whitney U-test (nonparametric data). Comparisons of categorical data were done by chi-square tests. Variables with p < 0.1 in univariate analysis were further analyzed using multiple logistic regression. No automated or manual variable selection methods were used.

Results

  1. Top of page
  2. Abstract
  3. Continuing Medical Education
  4. Methods
  5. Results
  6. Discussion
  7. Limitations
  8. Conclusions
  9. References

A total of 619 patients were included in this study (Figure 1). The median age of the study population was 72 years (interquartile range [IQR] = 66 to 79 years). Fifty-seven percent (353) were men. The median time from symptom onset to ED arrival was 7.3 hours (IQR = 5.5 to 9.7 hours; range = 0.2–11.75 hours). The median GCS on arrival was 14 (IQR = 13 to 15). Most patients (n = 569, 91.9%) had the total ED stay time within the range of 2 to 6 hours. Other detailed characteristics of patients with and without ED neurologic deterioration are shown in Table 1. Among the 619 enrolled patients, 140 (22.6%) experienced ED neurologic deterioration. The agreement of ED neurologic deterioration detection between different emergency physicians was high (kappa value = 0.9).

image

Figure 1.  The enrollment strategies of the study. GCS = Glasgow Coma Scale; SICH = spontaneous intracerebral hemorrhage.

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Table 1.    Univariate and Multivariate Analyses of Factors Associated With ED Neurologic Deterioration in Noncomatose SICH Patients
CharacteristicsPatients With ED Neurologic Deterioration (n = 140)Patients Without ED Neurologic Deterioration (n = 479)p-valueMultiple Logistic Regression OR (95% CI)
  1. Results expressed as number (%) for categorical variables and mean (±SD) for numerical variables.

  2. dBP = diastolic blood pressure; GCS = Glasgow Coma Scale; IVH = intraventricular hemorrhage; MAP = mean arterial pressure; NA = not applicable; PP = pulse pressure; sBP = systolic blood pressure; SICH = spontaneous intracerebral hemorrhage.

  3. *p < 0.1 (univariate analysis)

  4. †p < 0.05 (multiple logistic regression).

Demographic variables
 Age ≥ 65 yr115 (82.1)390 (81.4)0.902 
 Male sex 84 (60.0)269 (56.2)0.439 
 Current smoker 42 (30.0)126 (26.3)0.389 
 Diabetes 51 (36.4)147 (30.7)0.217 
 Coronary artery disease 36 (27.6)132 (25.7)0.376 
 Congestive heart failure history* 35 (25.0) 86 (17.9)0.0891.49 (0.88–2.50)
 Hypertension110 (78.6)365 (76.2)0.387 
 Regular antiplatelet use*† 55 (39.3)135 (28.2)0.0162.07 (1.20–3.55)
Initial ED assessments
 Time from ictus < 3 hours*† 38 (27.1) 89 (18.6)0.0322.12 (1.29–3.50)
 Initial ED GCS < 15* 79 (56.4)217 (45.3)0.0211.09 (0.65–1.86)
 sBP (mmHg)*209 ± 19205 ± 19 0.0641.49 (0.98–1.92)
 dBP (mmHg) 99 ± 1796 ± 190.223 
 PP (mmHg)110 ± 13109 ± 13 0.293 
 MAP (mmHg) 136 ± 17133 ± 18 0.134 
 Pulse rate (beats/min)74 ± 9 73 ± 9 0.201 
 Respiratory rate (breaths/min)19 ± 3 20 ± 3 0.197 
 Body temperature ≥ 37 °C*† 56 (40.0)137 (28.6)0.0131.72 (1.12–2.63)
 Atrial fibrillation  25 (17.9) 85 (17.7)0.532 
 QTc prolongation 20 (14.3) 74 (15.4)0.790 
Initial laboratory studies
 Serum sodium (mmol/L)141.1 ± 5.5 140.6 ± 5.90.363 
 Serum potassium (mmol/L)  4.3 ± 0.7   4.4 ± 0.80.828 
 Creatinine (mmol/L)  1.5 ± 1.2   1.6 ± 0.90.813 
 Blood sugar (mg/dL) 144.9 ± 65.0  139.7 ± 73.10.614 
 Hemoglobin (gm/dL) 11.1 ± 1.1  11.2 ± 1.20.292 
 Platelet count (×1010)/L  28.9 ± 12.6   30.9 ± 14.10.138 
 Prothrombin time (seconds) 11.4 ± 0.8  11.5 ± 0.60.202 
 Partial thromboplastin time (seconds) 32.4 ± 2.8  32.2 ± 2.00.451 
Brain image findings
 Infratentorial hemorrhage* 31 (22.1) 65 (13.6)0.0171.32 (0.82–2.13)
 Hematoma volume ≥ 30 mL* 52 (37.1)125 (26.1)0.0141.47 (0.76–2.86)
 IVH*† 51 (36.4)128 (26.7)0.0343.48 (2.13–5.69)
 Midline shift*† 68 (48.6)137 (28.6)<0.0013.63 (2.25–5.88)
ED treatments
 Osmotic agent133 (95.0)422 (88.1)0.018NA
 Antiepileptics 46 (32.9)112 (23.4)0.008NA
 Antihypertensives124 (88.6)369 (77.0)0.003NA
 ED stay ≥ 4 hours 47 (33.6)170 (35.5)0.689 
Prognosis
 Surgery  91 (65.0) 53 (11.1)<0.001NA
 1-week mortality 15 (11.0)12 (2.5)<0.001NA
 30-day mortality 51 (36.4) 94 (19.6)<0.001NA
 Modified Rankin Scale ≤ 2 on discharge 26 (18.6)203 (42.4)<0.001NA

Hematoma growth was considered to be the main cause of ED neurologic deterioration in 115 patients (82.1%). Multivariate analyses revealed that the independent predictors of ED neurologic deterioration were regular antiplatelet use, ictus to ED under 3 hours, initial body temperature of ≥37.5°C, IVH, and presence of a midline shift on CT (Table 1).

Patients with ED neurologic deterioration had a higher rate of requiring osmotic agents (such as mannitol), antiepileptics, and antihypertensive agents. They also had a higher rate of receiving surgical intervention, higher rates of 1-week and 30-day mortality, and a lower rate of good neurologic outcome on discharge, when compared with those without ED neurologic deterioration (Table 1). Using multiple logistic regression to control for potential confounders we found that ED neurologic deterioration was independently associated with 1-week mortality, 30-day mortality, and a bad neurologic outcome at discharge (Table 2).

Table 2.    The Significance of ED Neurologic Deterioration in Predicting Outcomes of Noncomatose SICH Patients
PredictorsORp-value95% CI
  1. SICH = spontaneous intracerebral hemorrhage.

Predictors of 1-week mortality
 Infratentorial hemorrhage2.380.0051.05–5.39
 Midline shift2.260.0081.05–4.86
 ED neurologic deterioration7.41<0.0013.24–16.97
Predictors of in-hospital mortality
 Smoker 1.660.0171.04–2.65
 Midline shift2.140.0031.17–3.91
 Hematoma volume ≥ 30 mL2.120.0021.34–3.34
 ED neurologic deterioration2.46<0.0011.48–4.08
Predictors of poor neurologic outcome on discharge
 Age ≥ 65 years1.630.0231.08–2.47
 Hematoma ≥ 30 mL2.030.0071.34–3.08
 Infratentorial hemorrhage1.650.0211.04–2.61
 Midline shift5.18<0.0012.86–9.36
 ED neurologic deterioration2.000.0151.17–3.43

Discussion

  1. Top of page
  2. Abstract
  3. Continuing Medical Education
  4. Methods
  5. Results
  6. Discussion
  7. Limitations
  8. Conclusions
  9. References

Previous investigations of early neurologic deterioration in SICH have not specifically evaluated patients with ED neurologic deterioration, although in a few instances it has been incorporated into the study’s definition of total neurologic deterioration.2–5,8,13 To the best of our knowledge this was the first study that attempted to delineate the clinical characteristics of ED neurologic deterioration in SICH patients.

We found that nearly a quarter of all patients presenting with SICH suffer from neurologic deterioration in the ED. Those with ED neurologic deterioration had higher rates of mortality and worse neurologic outcomes. This emphasizes the importance of close monitoring of patients with this highly morbid and mortal condition.

In this study, we did not evaluate methods for preventing ED neurologic deterioration. However, if we could determine which patients are at increased risk for, or are experiencing ED neurologic deterioration, optimizing care bundles and aggressively managing potential harmful factors might be beneficial. Adequate blood pressure control is an important component of ED SICH management.1,14 Previous evidence suggests that poor blood pressure control in the ED correlates with poor outcome.14 This is one area that may benefit those at high risk for ED neurologic deterioration.

Intraventricular hemorrhage was an important predictor for ED neurologic deterioration in this study, and in many previous studies, it was shown to be an important contributor to poor outcome.3,10,15–17 Most of the deterioration seen was related either to progression of IVH or development of hydrocephalus.16,17 Some recent studies had demonstrated the potential benefit of early surgical intervention (external ventricular drainage or clot removal) in selected IVH patients.10,16–18

Hematoma growth is the most important cause of neurological worsening in this cohort. Clinical predictors of hematoma growth have been widely studied, but the results of these studies were inconclusive.5,6,8 Recently, some studies demonstrated a more direct method to predict hematoma growth by identifying the signs of contrast extravasation in contrast-enhanced brain CT.19,20 Since contrast-enhanced CT was not a routine procedure in evaluating stroke patients in the ED, this variable was not analyzed in our study. However, this potential predictor deserves prospective study to determine its predictive significance in both ED neurologic deterioration and other prognostic targets.

Limitations

  1. Top of page
  2. Abstract
  3. Continuing Medical Education
  4. Methods
  5. Results
  6. Discussion
  7. Limitations
  8. Conclusions
  9. References

To simplify the definition of ED neurologic deterioration and to get the best variable availability, we did not use relatively minor neurologic deterioration (e.g., muscle power decrease) as criteria for ED neurologic deterioration. As a result, the ED neurologic deterioration predictors could only predict a more than two-point decrease in consciousness in the GCS score among SICH patients with an initial ED GCS score ≥ 13. Including all two-point decreases in GCS as ED neurologic deterioration might risk overestimating the incidence of significant neurologic deterioration because of inter-rater variability among various health care providers in GCS score assessment.21 Some studies used a more than four-point decrease in GCS score to define neurologic deterioration, to avoid this overestimation.3 However, to conform with the usual definition of neurologic deterioration used in clinical practice, and to stay in agreement with definition rationale in other literature,2,7 we used a two-point decrease in the GCS score.

Second, the diagnostic and therapeutic interventions were not rigorously standardized due to the nature of retrospective design; this might have resulted in omission of data or erroneous data in some analyzed variables. Fortunately, most analyzed variables were simply the basic data required to complete a registry data sheet and medical chart when treating ICH patients in this protocol-driven care system. The patients who we excluded due to loss of important data were few and were believed to be randomly distributed between the patients with and without ED neurologic deterioration.

Third, the incidence of ED neurologic deterioration in this study might represent the condition of SICH patients with specific ED stay time. In other words, the incidence might be higher in EDs with longer stay times and lower in those with shorter stay times, although we believe most EDs have similar average stay times for SICH patients due to the similar guidelines and stay times recorded in previous studies.14

Conclusions

  1. Top of page
  2. Abstract
  3. Continuing Medical Education
  4. Methods
  5. Results
  6. Discussion
  7. Limitations
  8. Conclusions
  9. References

The incidence of ED neurologic deterioration was 22.6% in this cohort. Predictors of ED neurologic deterioration included presentation within 3 hours, midline shift, intraventricular hemorrhage, fever, and prior use of antiplatelet agents. ED neurologic deterioration was a strong determinant of poor outcome. Efforts should be made to optimize efficacy and quality of care for patients at high risk for ED neurologic deterioration, although determining optimal resuscitation strategies for improving outcome requires further study.

References

  1. Top of page
  2. Abstract
  3. Continuing Medical Education
  4. Methods
  5. Results
  6. Discussion
  7. Limitations
  8. Conclusions
  9. References