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Emergency Department Control of Blood Pressure in Intracerebral Hemorrhage
The Journal of Emergency Medicine, Vol. 41, No. 4, pp. 355–361, 2011 Copyright © 2011 Published by Elsevier Inc. Printed in the USA 0736-4679/$–see front matter
doi:10.1016/j.jemermed.2009.02.001
Original Contributions
EMERGENCY DEPARTMENT CONTROL OF BLOOD PRESSURE IN INTRACEREBRAL HEMORRHAGE Samantha K. Honner, MD,* Amandeep Singh, MD,* Paul T. Cheung, MPH,* Harrison J. Alter, Claudine G. Dutaret, MD,† Atul K. Patel, MD,‡ and Ananth Acharya, MD†
MD,*
*Department of Emergency Medicine, †Division of Neurology, Department of Medicine, and ‡Division of Neurosurgery, Department of Surgery, Alameda County Medical Center, Oakland, California Reprint Address: Amandeep Singh, MD, Department of Emergency Medicine, Alameda County Medical Center, 1411 East 31st Street, Oakland, CA 94611
e Keywords—intracerebral hemorrhage; hypertension; therapy
e Abstract—Background: Early treatment of elevated blood pressure (BP) in patients presenting with spontaneous intracerebral hemorrhage (ICH) may decrease hematoma enlargement and lead to better neurologic outcome. Study Objective: To determine whether early BP control in patients with spontaneous ICH is both feasible and tolerated when initiated in the Emergency Department (ED). Methods: A single-center, prospective observational study in patients with spontaneous ICH was performed to evaluate a protocol to lower, and maintain for 24 h, the mean arterial pressure (MAP) to a range of 100 –110 mm Hg within 120 min of arrival to the ED. An additional goal of placing a functional arterial line within 90 min was specified in our protocol. Hematoma volume, neurologic disability, adverse events, and in-hospital mortality were recorded. Results: A total of 22 patients were enrolled over a 1-year study period. The average time to achieve our target MAP after implementation of our protocol was 123 min (range 19 –297 min). The average time to arterial line placement was 84 min (range 36 –160 min). Overall, 77% of the patients tolerated the 24-h protocol. The in-hospital mortality rate in this group of patients was 41%. Conclusions: Adopting a protocol to reduce and maintain the MAP to a target of 100 –110 mm Hg within 120 min of ED arrival was safe and well tolerated in patients presenting with spontaneous ICH. If future trials demonstrate a clinical benefit of early BP control in spontaneous ICH, EDs should implement similar protocols. © 2011 Published by Elsevier Inc.
RECEIVED: 26 August 2008; FINAL ACCEPTED: 5 February 2009
SUBMISSION RECEIVED:
INTRODUCTION Spontaneous intracerebral hemorrhage (ICH) is seen in more than 67,000 patients per year in the United States and results in unacceptably high mortality and neurologic morbidity. The 30-day reported mortality rate of these patients is between 35% and 52%, with half of all deaths occurring within the first 2 days. The majority of surviving patients are left with severe disability, with only 20% of individuals returning to a level of functional independence at 6 months (1). Contemporary theory regarding the pathogenesis of the initiation and propagation of ICH focuses on the role of intravascular fibrinoid necrosis creating “vulnerable” rupture sites at or near the bifurcation of susceptible intracranial arterioles. Chronic hypertension further reduces vascular compliance and increases the likelihood of spontaneous rupture (2). Persistently elevated blood pressure (BP) is thought to contribute to the propagation of ICH through early hematoma expansion and rebleeding. Early hematoma growth is seen in nearly one-third of all patients, most commonly in the first several hours from symptom onset, and is a poor prognostic indicator (3–9).
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Despite increasing data suggesting that elevated BP in patients with ICH is associated with early hematoma growth, poor neurologic outcome, and death, there are no evidence-based guidelines supporting a specific treatment algorithm for managing the elevated BP in these patients. The 2007 American Stroke Association/American Heart Association guidelines on the management of ICH give a class IIb recommendation (i.e., usefulness/efficacy less well established by evidence or opinion) with a level of evidence C (i.e., consensus opinion of experts) to “consider a modest reduction of blood pressure” if the mean arterial pressure (MAP) is elevated ⬎ 130 mm Hg and to “consider aggressive reduction of blood pressure” if the MAP is ⬎ 150 mm Hg (1). The goal of our study was to assess the feasibility and tolerability of early BP reduction in patients with elevated BP and spontaneous ICH in an Emergency Department (ED) setting. Secondary goals evaluated the following outcomes: change in hematoma volume at 24 h, in-hospital mortality, and functional neurologic outcome at 24 h and 3 months.
MATERIALS AND METHODS Study Design This was a prospective observational study conducted at a single hospital from January 15, 2007 to January 15, 2008 using a multidisciplinary protocol developed jointly by the Department of Emergency Medicine and the Divisions of Neurology, Neurosurgery, and Critical Care. The study was approved by the hospital institutional review board committee. Informed consent was waived, as this was a feasibility and safety study regarding an intervention that was routinely recommended by the Divisions of Neurology and Neurosurgery at our hospital.
Study Setting and Patients Alameda County Medical Center, Highland Campus in Oakland, California, is an urban teaching hospital with an affiliated emergency medicine residency-training program that treats approximately 72,000 patients per year in the ED. All adult patients with a spontaneous ICH, determined by non-contrast head computed tomography (CT) scan, who presented during the study period and who had a triage MAP ⬎ 120 mm Hg were eligible for inclusion. Exclusion criteria included age ⬍ 18 years, pregnancy, coagulopathy (bleeding disorder, low-molecular weight heparin or warfarin therapy, platelet count ⬍ 50,000/
mm3, or international normalized ratio ⬎ 2.0), pre-existing neurologic disability (e.g., requiring assistance for activities of daily living), symptom onset ⬎ 48 h before being seen in the ED, or a history (e.g., trauma) or CT scan suggesting secondary ICH (e.g., vascular malformation, aneurysm, tumor). Patients who had a head CT scan performed more than 90 min after ED arrival or who were transferred from another facility to our hospital were also excluded.
Study Protocol Our management protocol specified that patients judged to be eligible by the treating emergency physician should have their MAP lowered to a target of 100 –110 mm Hg within 120 min of presentation to the ED and maintain this target MAP at this level for a minimum of 24 h. We also specified a goal of placing a functional arterial line within 90 min of patient arrival. Antihypertensive treatment before the placement of the arterial line was recommended. The choice of antihypertensive agent was left to the discretion of the treating emergency physician. Doses for the hospital-preferred hypertensive medications (esmolol, fenoldapam, labetalol, nicardipine) and the hospital protocols for use of recombinant factor VIIa and human coagulation factor IX complex were provided. All patients were monitored in a critical care room in the ED and admitted to the intensive care unit for cardiovascular and neurologic monitoring. A repeat head CT scan was obtained at 24 h, or sooner in cases of neurologic deterioration. CT scans were performed on a 512 ⫻ 512 matrix with a 5-mm slice thickness.
Measurements We collected data using standardized collection forms. The ED data were collected by the treating emergency physician or, if present, the consulting neurologist or neurosurgeon. The initial data collection included patient demographic information, past medical history, risk factors for ICH, time of symptom onset, Glasgow Coma Scale (GCS) score, and National Institute of Health Stroke Scale (NIHSS) score. Time to obtain target MAP, time to functional arterial line placement, antihypertensive agent(s) used, and 24-h complications were also recorded. The consulting neurologist or neurosurgeon collected the inpatient data. This included antihypertensive agent(s) used or discontinued, GCS and NIHSS scores at 24 h and discharge, and in-hospital unexpected events. After the enrollment period, a board-certified neurologist, adept in the ability to measure intracranial
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hematoma volume, interpreted the initial and subsequent head CT scans. One of the authors (SH) contacted each patient at 3 months to determine the modified Rankin score (mRS).
Outcomes The primary goal of our study was to address the feasibility and tolerability of early aggressive BP management for patients with spontaneous ICH who present to the ED. Secondary goals evaluated the following outcomes: change in hematoma volume at 24 h, in-hospital mortality, and functional neurologic outcome at 24 h and 3 months. Feasibility was evaluated through the ability to obtain the target MAP of 100 –110 mm Hg within 120 min from ED presentation and to maintain the target MAP at 100 – 110 mm Hg for 24 h. Patients that did not incur any adverse effects requiring termination of therapy within the first 24 h were considered to have tolerated the protocol. Hematoma volume was calculated using the maximum CT diameter measurements inserted into this formula: [0.5 * (length [cm]) * (width [cm]) * (height [cm])]. This method has been found to correlate highly with volumes calculated by planimetric methods for all hemorrhagic locations (10). The change in hematoma size was calculated as a percentage using the formula: [(final volume ⫺ initial volume)/initial volume] * 100. Significant hematoma expansion was defined as an increase in the volume of intraparenchymal hemorrhage by more than 33% on the repeat head CT scan compared to the baseline CT scan (11). Neurologic outcomes at 24 h and hospital discharge were evaluated using the GCS and NIHSS scales (12,13). Functional neurologic outcome at 3 months was assessed with the mRS (14).
Data Analysis Descriptive statistics were derived using SPSS (version 11; SPSS, Inc., Chicago, IL). Statistical significance was set at a level of 0.05 and determined using the Student’s t-test for paired comparisons.
RESULTS During the 1-year study period, a total of 60 patients with ICH were screened for enrollment. After exclusion criteria were applied, 23 patients were eligible for patient enrollment (Figure 1). Twenty-two of these patients were successfully enrolled and comprise the study population.
Figure 1. Patient enrollment.
Clinical and demographic information regarding the study population is listed in Table 1. Patients ranged in age from 33 to 83 years (mean age 54.7 years). Half of
Table 1. Clinical and Demographic Characteristics (n ⴝ 22) Characteristics Age in years, Mean (SD) Female gender Race African-American Hispanic Asian Caucasian Past medical history Hypertension Cocaine* Diabetes Prior stroke Cardiac disease† Tobacco Hyperlipidemia Hematoma location‡ Basal ganglia Thalamus Pons/midbrain Lobar Cerebellum
n (%) 54.7 (11.3) 11 (50.0) 10 (45.5) 6 (27.3) 5 (22.7) 1 (4.5) 17 (77.3) 9 (40.9) 6 (27.3) 5 (22.7) 3 (13.6) 2 (9.1) 1 (4.5) 8 (33.3) 8 (33.3) 4 (16.7) 3 (12.5) 1 (4.2)
* Per history or urine toxicology. † Prior myocardial infarction or congestive heart failure. ‡ Two patients had two hematomas giving a total number of 24 hematomas.
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Table 2. Outcome Data (n ⴝ 22) Emergency Department Data Initial MAP in mm Hg Time from symptoms to arrival*† Time from ED arrival to CT scan† Time from arrival to arterial line† Time from arrival to target MAP†
Initial hematoma volume in cm3 Initial GCS Initial NIHSS Neurologic outcome data‡ 24-h GCS 24-h NIHSS 3-month mRS
Table 3. Radiologic and Neurologic Data of Survivors (n ⴝ 13) Mean (SD) 152.4 (24.9) 49.6 (29.7) 41.1 (19.3) 84.7 (36.7) 123.4 (72.9) Median (IQR) 17.9 (10.5–29.6) 11 (7–15) 19 (15–26) 10 (3–14) 26 (13–38) 5 (3–6)
* Unknown for 5 patients. † Times are given in minutes. ‡ Data available for 21 patients. MAP ⫽ mean arterial pressure; ED ⫽ Emergency Department; CT ⫽ computed tomography; GCS ⫽ Glasgow Coma Scale score; NIHSS ⫽ National Institute of Health Stroke Scale score; mRS ⫽ modified Rankin score.
the enrolled patients were female. A history of hypertension was seen in over 75% of enrolled patients, with 41% identifying positive for cocaine use. Two-thirds of the intracranial hemorrhages were located in the basal ganglia and thalamus. There was CT evidence of hemorrhage extension into the ventricles in 11 cases (50%), and hydrocephalus present in 6 cases (27%). Patients arrived, on average, 50 min (range 23–78 min) from the time of symptom onset. Nearly 80% of the patients received a CT scan within 60 min of arrival to the ED. The median initial intracranial hematoma volume was 17.9 cm3 (interquartile ratio [IQR] 10.5–29.6 cm3). Emergent ventriculostomy in the first 24 h was performed in 1 patient. Three patients received factor VIIa in the ED. The average time from arrival in the ED to target MAP was 123 min (range 19 –297 min) (Table 2). The target of reducing the MAP to a level between 100 and 110 mm Hg within 120 min of arrival to the ED was obtained in 11 of the 22 cases (50%). Seventeen patients (77%) achieved the MAP target within 170 min, and 20 patients (91%) achieved the target within 200 min. Fourteen of the 22 patients (68%) required multiple agents to reach the target MAP. The most commonly used regimen included an initial bolus therapy with labetalol followed by a nicardipine drip. A total of 16 patients received continuous nicardipine (73%) and 12 patients received intermittent or continuous labetalol (55%). One patient had spontaneous regression of their MAP to the target range and did not require any antihypertensive therapy. The mean time to functional arterial line placement was 84 min (range 36 –160 min). The goal of placing a
Median (IQR) Radiologic data* Initial hematoma volume in cm3 Repeat hematoma volume in cm3 Neurologic data Initial GCS Initial NIHSS 24-hour GCS 24-hour NIHSS Discharge GCS Discharge NIHSS 3-month mRS
11.0 (7.5–19) 11.5 (9.1–16) 15 (11–15) 16 (10–18) 14 (12–15) 13 (12–21) 15 (15) 10 (6–11) 3 (2–4)
* One survivor did not have a repeat computed tomography scan. IQR ⫽ interquartile range; GCS ⫽ Glasgow Coma Scale score; NIHSS ⫽ National Institute of Health Stroke Scale score; mRS ⫽ modified Rankin score.
functional arterial line within 90 min of arrival was obtained in 12 of the 22 cases (55%). Eighteen patients (82%) received a functional arterial line within 110 min. Reasons for delay in achieving our target MAP and arterial line included: difficult intravenous (i.v.) access (4 patients), resistant hypertension (4 patients), difficulty in obtaining a definitive airway (3 patients), pharmacy delay in delivering antihypertensive medications (3 patients), and a delay in obtaining the CT scan (2 patients). The median initial hematoma volume, GCS and NIHSS scores, and 24-h neurological outcomes are outlined in Table 2. The median 3-month mRS was 5 (IQR 3– 6). The median initial hematoma volume of surviving patients was 11.0 cm3 (IQR 7.5–19 cm3) compared to 31.7 cm3 (IQR 22.3– 40.5 cm3) in non-survivors (p ⫽ 0.02). Surviving patients had a lower percentage of intraventricular extension (38%) compared with nonsurvivors (67%). The median initial GCS of surviving patients was 15 (IQR 11–15), compared to 6 (IQR 4 – 8) in non-survivors (p ⫽ 0.00). The median 24-h repeat hematoma volume for survivors was 11.5 cm3 (IQR 9.1–16 cm3) (p ⫽ 0.35 compared to initial hematoma volume) (Table 3). The 24-h median proportional hematoma growth in survivors was 4.5%. Significant 24-h intracranial hematoma expansion occurred in 2 patients (17%). Our protocol for BP management was well tolerated in 17 of the 22 cases (77%). Five patients required vasopressors in the first 24 h for hypotension after the antihypertensive therapy was weaned off (Table 4). Two additional patients experienced in-hospital adverse events. In one patient, pneumonia was recognized on hospital day 2. In the second patient, hydrocephalus requiring a ventriculostomy, transient renal insufficiency, and an ileus developed during
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Table 4. Timing of BP Control and Pressors for Non-Survivors (n ⴝ 9) Case
Goal MAP*
Vasopressors in the First 24 h (Time of Onset)†
Time of Death†
1 2 5‡ 6 12 13 17 21 22
1:50 1:40 0:36 2:50 2:24 4:57 3:07 0:19 1:34
No No Yes (2) Yes (16) Yes (14) No No Yes (14; stopped at 19) Yes (20)
26 60 24 21 25 29 103 44 36
* Time in hours:minutes from ED presentation. † Time in hours from ED presentation. ‡ This patient did not receive any antihypertensive agents. BP ⫽ blood pressure; MAP ⫽ mean arterial pressure.
the first week of hospitalization. Both of these patients survived. Nine patients died during hospitalization (in-hospital mortality 41%), with a majority occurring within 48 h of presentation. A tenth patient died 2 months after study enrollment. DISCUSSION In 2007, the American Stroke Association/American Heart Association updated their recommendations for BP control in patients with spontaneous ICH (1). A class IIb recommendation, based mainly on consensus opinion, concludes that “aggressive reduction” of the BP with continuous i.v. antihypertensive infusion should be considered in patients with MAP ⬎ 150 mm Hg and that a “modest reduction” of the BP with continuous or intermittent i.v. antihypertensive medication should be considered in patients with MAP ⬎ 130 mm Hg. These recommendations are based on a handful of studies that have shown a correlation between elevated initial BP in ICH and early intracranial hematoma expansion, neurologic morbidity, and mortality (3–9). Unlike acute ischemic stroke, pharmacologic regulation of MAP does not adversely affect regional cerebral blood flow or intracranial pressure in experimental models (15,16). The recent results of the INTERACT (Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage) trial support the notion that early BP control in patients with elevated BP and spontaneous ICH is warranted (17). In this prospective multicenter trial, patients were enrolled within 6 h of symptom onset and randomized to receive early intensive lowering of BP (target systolic BP 140 mm Hg) vs. standard care (target systolic BP 180 mm Hg). Patients in the intensive lowering of BP group had smaller volume of hematoma growth compared to pa-
tients receiving usual care (13.7% mean proportional hematoma growth in intensive care group compared to 36.3% in the standard care group; p ⫽ 0.04) at 24 h. A non-significant trend favoring mortality was seen in the intensive care group (overall mortality 10% vs. 13% in the standard care group). Several additional studies support the notion of early BP management in the treatment of spontaneous ICH in the ED. A retrospective chart review by Burke et al. found that patients with spontaneous ICH treated with antihypertensives in the first 6 h from initial presentation had a significant reduction in mortality compared to patients not treated in this time frame (18). A study by Qureshi et al. observed that patients with spontaneous ICH treated within 6 h of symptom onset were more likely to be functionally independent as judged by the mRS, compared to patients who were treated between 6 and 24 h (19). In our prospective series of 22 patients with spontaneous ICH presenting to a single institution, an ED protocol with aims to place an arterial line within 90 min of presentation and to reduce the MAP to 100 –110 mm Hg within 120 min of presentation was feasible in only 50% of patients. The average time from patient arrival in the ED to successful arterial line placement and target MAP was 84 min and 123 min, respectively. Although only 50% of our patients achieved a target MAP of 100 –110 mm Hg using our pre-specified goal of 120 min, over 90% of our patients reached this goal with an additional 80 min of therapy. A prior study by Koch et al. has shown that the MAP can be safely lowered to a level of ⬍ 110 mm Hg in patients with spontaneous ICH (20). The average time to target MAP in our study compares favorably to this study (123 min ⫾ 73 min compared to 163 min ⫾ 164 min in the Koch et al. study) (20). The majority of delays to achieving our target MAP and functional arterial line were due to delays in obtaining i.v. access, definitive airway control, and head CT scan, as well as delays in pharmacy delivery of antihypertensive medication. Our protocol was tolerated in over three-quarters of our patients per our study definition, as 5 patients required vasopressor therapy in the first 24 h. In all but one of these patients, vasopressors were started more than 14 h after initial ED presentation, long after the goal MAP was obtained. The one patient who required vasopressors within 2 h of presentation never received any antihypertensive medication (Table 4). Although all of these patients died, their mortality is unlikely to be related to rapid blood pressure lowering in the ED. It is more likely to be related to their larger hematoma volumes, higher rates of intraventricular extension, and lower GCS scores than the survivors, as these are the most important predictors of mortality from ICH (21).
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The observed mortality of 41%, with most deaths occurring the first 2 days, is consistent with prior studies (1,2,6,18,19,22). The 24-h median proportional hematoma growth in patients that survived was 4.5%. This impressive result is similar to results seen with intensive BP reduction group from the INTERACT trial (13.7% mean proportional hematoma growth compared to 36.3% in the standard care group, p ⫽ 0.04) (17). Neurological outcome in this group was also favorable, with a 3-month mRS of 3 (IQR 2– 4).
Limitations Given the observational nature of our study, we cannot conclude that aggressive BP control in the ED leads to reduced hematoma growth or improved clinical outcomes. Our design was to assess the feasibility and tolerability of achieving a MAP target of 100 –110 mm Hg in patients with spontaneous ICH who present to the ED with a MAP ⬎ 120 mm Hg. To this end, we have shown that these goals are possible in over 90% of patients in under 3½ hours. Although we successfully enrolled ⬎ 95% of eligible patients who presented in a 1-year study period, we were able to test our hypothesis in only 22 patients. This sample size of 22 patients is slightly smaller than those of two prospective studies by Qureshi et al. that enrolled 27 and 35 patients, respectively, and significantly smaller than the 404 patients enrolled in the INTERACT trail (17,19,22). Other limitations include interobserver bias, as emergency physicians obtained the initial GCS and NIHSS scores, and a neurologist or neurosurgeon obtained the subsequent scores. There was no assessment of interrater reliability between the different physicians. Finally, the physicians collecting the data and the neurologist reading the CT scan were not blinded to the study objectives.
CONCLUSION Our study shows that a protocol of early BP control in the ED for patients with spontaneous ICH is both feasible and safe. The observational nature of our study prevents us from definitively concluding that our protocol led to an improvement in hematoma volume or neurologic outcome compared to standard therapy. The results from the upcoming Antihypertensive Treatment of Acute Cerebral Hemorrhage trial and the follow-up to the Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage (INTERACT-2) trial should give us an evidence-
based answer to the question of whether aggressive BP control in patients with spontaneous ICH leads to better clinical outcome.
REFERENCES 1. Broderick J, Connolly S, Feldmann E, et al. Guidelines for the management of spontaneous intracerebral hemorrhage in adults: 2007 update: a guideline from the American Heart Association/ American Stroke Association Stroke Council, High Blood Pressure Interdisciplinary Working Group: the American Academy of Neurology affirms the value of this guideline as an education tool for neurologists. Stroke 2007;38:2001–23. 2. Qureshi AI, Tuhrim S, Broderick JP, Batjer HH, Hondo H, Hanley DF. Spontaneous inracerebral hemorrhage. N Engl J Med 2001; 344:1450 – 60. 3. Kazui S, Naritomi H, Yamamoto H, Sawada T, Yamaghuchi T. Enlargement of spontaneous intracerebral hemorrhage: incidence and time course. Stroke 1996;26:1783–7. 4. Ohwaki K, Yano E, Nagashima H, Hirata M, Nakagomi T, Tamura A. Blood pressure management in acute intracerebral hemorrhage: Relationship between elevated blood pressure and hematoma enlargement. Stroke 2004;35:1364 –7. 5. Brott T, Broderick J, Kothari R, et al. Early hemorrhage growth in patients with intracerebral hemorrhage. Stroke 1997;28:1–5. 6. Dandapani BK, Suzuki S, Kelley RE, Iglesias YR, Duncan RC. Relation between blood pressure and outcome in intracerebral hemorrhage. Stroke 1995;26:21– 4. 7. Leira R, Davalos A, Silva Y, et al. Early neurologic deterioration in intracrerebral hemorrhage: predictors and associated factors. Neurology 2004;63:461–7. 8. Barton CW, Hemphill JC. Cumulative dose of hypertension predicts outcome in intracranial hemorrhage better than American Heart Association guidelines. Acad Emerg Med 2007;14: 695–701. 9. Willmot M, Leonardi-Bee J, Bath PMW. High blood pressure in acute stroke and subsequent outcome: a systematic review. Hypertension 2004;43:18 –24. 10. Kothari R, Brott T, Broderick J, et al. The ABCs of measuring intracerebral hemorrhage volumes. Stroke 1996;27:1304 –5. 11. Leira R, Davalos A, Silva Y, et al. Early neurologic deterioration in intracrerebral hemorrhage: predictors and associated factors. Neurology 2004;63:461–7. 12. Teasdale G, Jannett B. Assessment of coma and impaired consciousness: a practical scale. Lancet 1974;2:81– 4. 13. Brott T, Adams HP Jr, Olinger CP, et al. Measurements of acute cerebral infarction: a clinical examination scale. Stroke 1989;20: 864 –70. 14. Bamford JM, Sandercock PA, Warlow CP, Slattery J. Interobserver agreement for the assessment of handicap in stroke patients. Stroke 1989;20:828. 15. Qureshi AI, Wilson DA, Hanley DF, Traystman RJ. Pharmacologic reduction of mean arterial pressure does not adversely effect regional cerebral blood flow and intracranial pressure in experimental intracerebral hemorrhage. Crit Care Med 1999;27: 965–71. 16. Powers WJ, Adams RE, Yundt KD, et al. Acute pharmacological hypotension after intracerebral hemorrhage does not change cerebral blood flow. Stroke 1999;30:242. 17. Anderson CS, Huang Y, Wang JG, et al. Intensive blood pressure reduction in acute cerebral haemorrhage trial (INTERACT): a randomized pilot study. Lancet Neurol 2008;7:391–9. 18. Burke RE, Dorfman M, Chan SB. Is emergent antihypertensive treatment beneficial in intracranial hemorrhage? J Emerg Med 2005;29:9 –13. 19. Qureshi A, Mohammad Y, Yahia A, Suarez J, et al. A prospective multicenter study to evaluate the feasibility and safety of aggressive antihypertensive treatment in patients with
ED Control of BP in Intracerebral Hemorrhage acute intracerebral hemorrhage. J Intensive Care Med 2005;20: 34 – 42. 20. Koch S, Romano JG, Forteza AM, Otero CM, Rabinstein AA. Rapid blood pressure reduction in acute intracerebral hemorrhage: feasibility and safety. Neurocrit Care 2008;8:316 –21.
361 21. Subramaniam S. Controversies in medical management of intracerebral hemorrhage. Can J Neurol Sci 2005;S2:S13–21. 22. Qureshi A, Harris-Lane P, Kirmani J, et al. Treatment of acute hypertension in patients with intracerebral hemorrhage using American Heart Association guidelines. Crit Care Med 2006;34:1975– 81.
ARTICLE SUMMARY 1. Why is this topic important? Hypertension is associated with early hematoma expansion, poor neurological outcome, and death in intracerebral hemorrhage. Recent studies have shown that early blood pressure control reduces hematoma growth and may decrease mortality. 2. What does this study attempt to show? This was a prospective observational trial testing the feasibility and tolerability of lowering mean arterial pressure to a range of 100 –110 mm Hg within 120 min of arrival in patients with spontaneous intracerebral hemorrhage in the Emergency Department (ED) setting. 3. What are the key findings? The average time for reaching our target mean arterial pressure was 123 min and for placing an arterial line was 84 min. The protocol was tolerated in 77% of patients, and our in-hospital mortality rate was 41%. 4. How is patient care impacted? If future trials demonstrate a clinical benefit of early blood pressure control in intracerebral hemorrhage, EDs could successfully implement similar protocols.
doi:10.1016/j.jemermed.2009.02.001
Original Contributions
EMERGENCY DEPARTMENT CONTROL OF BLOOD PRESSURE IN INTRACEREBRAL HEMORRHAGE Samantha K. Honner, MD,* Amandeep Singh, MD,* Paul T. Cheung, MPH,* Harrison J. Alter, Claudine G. Dutaret, MD,† Atul K. Patel, MD,‡ and Ananth Acharya, MD†
MD,*
*Department of Emergency Medicine, †Division of Neurology, Department of Medicine, and ‡Division of Neurosurgery, Department of Surgery, Alameda County Medical Center, Oakland, California Reprint Address: Amandeep Singh, MD, Department of Emergency Medicine, Alameda County Medical Center, 1411 East 31st Street, Oakland, CA 94611
e Keywords—intracerebral hemorrhage; hypertension; therapy
e Abstract—Background: Early treatment of elevated blood pressure (BP) in patients presenting with spontaneous intracerebral hemorrhage (ICH) may decrease hematoma enlargement and lead to better neurologic outcome. Study Objective: To determine whether early BP control in patients with spontaneous ICH is both feasible and tolerated when initiated in the Emergency Department (ED). Methods: A single-center, prospective observational study in patients with spontaneous ICH was performed to evaluate a protocol to lower, and maintain for 24 h, the mean arterial pressure (MAP) to a range of 100 –110 mm Hg within 120 min of arrival to the ED. An additional goal of placing a functional arterial line within 90 min was specified in our protocol. Hematoma volume, neurologic disability, adverse events, and in-hospital mortality were recorded. Results: A total of 22 patients were enrolled over a 1-year study period. The average time to achieve our target MAP after implementation of our protocol was 123 min (range 19 –297 min). The average time to arterial line placement was 84 min (range 36 –160 min). Overall, 77% of the patients tolerated the 24-h protocol. The in-hospital mortality rate in this group of patients was 41%. Conclusions: Adopting a protocol to reduce and maintain the MAP to a target of 100 –110 mm Hg within 120 min of ED arrival was safe and well tolerated in patients presenting with spontaneous ICH. If future trials demonstrate a clinical benefit of early BP control in spontaneous ICH, EDs should implement similar protocols. © 2011 Published by Elsevier Inc.
RECEIVED: 26 August 2008; FINAL ACCEPTED: 5 February 2009
SUBMISSION RECEIVED:
INTRODUCTION Spontaneous intracerebral hemorrhage (ICH) is seen in more than 67,000 patients per year in the United States and results in unacceptably high mortality and neurologic morbidity. The 30-day reported mortality rate of these patients is between 35% and 52%, with half of all deaths occurring within the first 2 days. The majority of surviving patients are left with severe disability, with only 20% of individuals returning to a level of functional independence at 6 months (1). Contemporary theory regarding the pathogenesis of the initiation and propagation of ICH focuses on the role of intravascular fibrinoid necrosis creating “vulnerable” rupture sites at or near the bifurcation of susceptible intracranial arterioles. Chronic hypertension further reduces vascular compliance and increases the likelihood of spontaneous rupture (2). Persistently elevated blood pressure (BP) is thought to contribute to the propagation of ICH through early hematoma expansion and rebleeding. Early hematoma growth is seen in nearly one-third of all patients, most commonly in the first several hours from symptom onset, and is a poor prognostic indicator (3–9).
7 November 2008; 355
356
S. K. Honner et al.
Despite increasing data suggesting that elevated BP in patients with ICH is associated with early hematoma growth, poor neurologic outcome, and death, there are no evidence-based guidelines supporting a specific treatment algorithm for managing the elevated BP in these patients. The 2007 American Stroke Association/American Heart Association guidelines on the management of ICH give a class IIb recommendation (i.e., usefulness/efficacy less well established by evidence or opinion) with a level of evidence C (i.e., consensus opinion of experts) to “consider a modest reduction of blood pressure” if the mean arterial pressure (MAP) is elevated ⬎ 130 mm Hg and to “consider aggressive reduction of blood pressure” if the MAP is ⬎ 150 mm Hg (1). The goal of our study was to assess the feasibility and tolerability of early BP reduction in patients with elevated BP and spontaneous ICH in an Emergency Department (ED) setting. Secondary goals evaluated the following outcomes: change in hematoma volume at 24 h, in-hospital mortality, and functional neurologic outcome at 24 h and 3 months.
MATERIALS AND METHODS Study Design This was a prospective observational study conducted at a single hospital from January 15, 2007 to January 15, 2008 using a multidisciplinary protocol developed jointly by the Department of Emergency Medicine and the Divisions of Neurology, Neurosurgery, and Critical Care. The study was approved by the hospital institutional review board committee. Informed consent was waived, as this was a feasibility and safety study regarding an intervention that was routinely recommended by the Divisions of Neurology and Neurosurgery at our hospital.
Study Setting and Patients Alameda County Medical Center, Highland Campus in Oakland, California, is an urban teaching hospital with an affiliated emergency medicine residency-training program that treats approximately 72,000 patients per year in the ED. All adult patients with a spontaneous ICH, determined by non-contrast head computed tomography (CT) scan, who presented during the study period and who had a triage MAP ⬎ 120 mm Hg were eligible for inclusion. Exclusion criteria included age ⬍ 18 years, pregnancy, coagulopathy (bleeding disorder, low-molecular weight heparin or warfarin therapy, platelet count ⬍ 50,000/
mm3, or international normalized ratio ⬎ 2.0), pre-existing neurologic disability (e.g., requiring assistance for activities of daily living), symptom onset ⬎ 48 h before being seen in the ED, or a history (e.g., trauma) or CT scan suggesting secondary ICH (e.g., vascular malformation, aneurysm, tumor). Patients who had a head CT scan performed more than 90 min after ED arrival or who were transferred from another facility to our hospital were also excluded.
Study Protocol Our management protocol specified that patients judged to be eligible by the treating emergency physician should have their MAP lowered to a target of 100 –110 mm Hg within 120 min of presentation to the ED and maintain this target MAP at this level for a minimum of 24 h. We also specified a goal of placing a functional arterial line within 90 min of patient arrival. Antihypertensive treatment before the placement of the arterial line was recommended. The choice of antihypertensive agent was left to the discretion of the treating emergency physician. Doses for the hospital-preferred hypertensive medications (esmolol, fenoldapam, labetalol, nicardipine) and the hospital protocols for use of recombinant factor VIIa and human coagulation factor IX complex were provided. All patients were monitored in a critical care room in the ED and admitted to the intensive care unit for cardiovascular and neurologic monitoring. A repeat head CT scan was obtained at 24 h, or sooner in cases of neurologic deterioration. CT scans were performed on a 512 ⫻ 512 matrix with a 5-mm slice thickness.
Measurements We collected data using standardized collection forms. The ED data were collected by the treating emergency physician or, if present, the consulting neurologist or neurosurgeon. The initial data collection included patient demographic information, past medical history, risk factors for ICH, time of symptom onset, Glasgow Coma Scale (GCS) score, and National Institute of Health Stroke Scale (NIHSS) score. Time to obtain target MAP, time to functional arterial line placement, antihypertensive agent(s) used, and 24-h complications were also recorded. The consulting neurologist or neurosurgeon collected the inpatient data. This included antihypertensive agent(s) used or discontinued, GCS and NIHSS scores at 24 h and discharge, and in-hospital unexpected events. After the enrollment period, a board-certified neurologist, adept in the ability to measure intracranial
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hematoma volume, interpreted the initial and subsequent head CT scans. One of the authors (SH) contacted each patient at 3 months to determine the modified Rankin score (mRS).
Outcomes The primary goal of our study was to address the feasibility and tolerability of early aggressive BP management for patients with spontaneous ICH who present to the ED. Secondary goals evaluated the following outcomes: change in hematoma volume at 24 h, in-hospital mortality, and functional neurologic outcome at 24 h and 3 months. Feasibility was evaluated through the ability to obtain the target MAP of 100 –110 mm Hg within 120 min from ED presentation and to maintain the target MAP at 100 – 110 mm Hg for 24 h. Patients that did not incur any adverse effects requiring termination of therapy within the first 24 h were considered to have tolerated the protocol. Hematoma volume was calculated using the maximum CT diameter measurements inserted into this formula: [0.5 * (length [cm]) * (width [cm]) * (height [cm])]. This method has been found to correlate highly with volumes calculated by planimetric methods for all hemorrhagic locations (10). The change in hematoma size was calculated as a percentage using the formula: [(final volume ⫺ initial volume)/initial volume] * 100. Significant hematoma expansion was defined as an increase in the volume of intraparenchymal hemorrhage by more than 33% on the repeat head CT scan compared to the baseline CT scan (11). Neurologic outcomes at 24 h and hospital discharge were evaluated using the GCS and NIHSS scales (12,13). Functional neurologic outcome at 3 months was assessed with the mRS (14).
Data Analysis Descriptive statistics were derived using SPSS (version 11; SPSS, Inc., Chicago, IL). Statistical significance was set at a level of 0.05 and determined using the Student’s t-test for paired comparisons.
RESULTS During the 1-year study period, a total of 60 patients with ICH were screened for enrollment. After exclusion criteria were applied, 23 patients were eligible for patient enrollment (Figure 1). Twenty-two of these patients were successfully enrolled and comprise the study population.
Figure 1. Patient enrollment.
Clinical and demographic information regarding the study population is listed in Table 1. Patients ranged in age from 33 to 83 years (mean age 54.7 years). Half of
Table 1. Clinical and Demographic Characteristics (n ⴝ 22) Characteristics Age in years, Mean (SD) Female gender Race African-American Hispanic Asian Caucasian Past medical history Hypertension Cocaine* Diabetes Prior stroke Cardiac disease† Tobacco Hyperlipidemia Hematoma location‡ Basal ganglia Thalamus Pons/midbrain Lobar Cerebellum
n (%) 54.7 (11.3) 11 (50.0) 10 (45.5) 6 (27.3) 5 (22.7) 1 (4.5) 17 (77.3) 9 (40.9) 6 (27.3) 5 (22.7) 3 (13.6) 2 (9.1) 1 (4.5) 8 (33.3) 8 (33.3) 4 (16.7) 3 (12.5) 1 (4.2)
* Per history or urine toxicology. † Prior myocardial infarction or congestive heart failure. ‡ Two patients had two hematomas giving a total number of 24 hematomas.
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Table 2. Outcome Data (n ⴝ 22) Emergency Department Data Initial MAP in mm Hg Time from symptoms to arrival*† Time from ED arrival to CT scan† Time from arrival to arterial line† Time from arrival to target MAP†
Initial hematoma volume in cm3 Initial GCS Initial NIHSS Neurologic outcome data‡ 24-h GCS 24-h NIHSS 3-month mRS
Table 3. Radiologic and Neurologic Data of Survivors (n ⴝ 13) Mean (SD) 152.4 (24.9) 49.6 (29.7) 41.1 (19.3) 84.7 (36.7) 123.4 (72.9) Median (IQR) 17.9 (10.5–29.6) 11 (7–15) 19 (15–26) 10 (3–14) 26 (13–38) 5 (3–6)
* Unknown for 5 patients. † Times are given in minutes. ‡ Data available for 21 patients. MAP ⫽ mean arterial pressure; ED ⫽ Emergency Department; CT ⫽ computed tomography; GCS ⫽ Glasgow Coma Scale score; NIHSS ⫽ National Institute of Health Stroke Scale score; mRS ⫽ modified Rankin score.
the enrolled patients were female. A history of hypertension was seen in over 75% of enrolled patients, with 41% identifying positive for cocaine use. Two-thirds of the intracranial hemorrhages were located in the basal ganglia and thalamus. There was CT evidence of hemorrhage extension into the ventricles in 11 cases (50%), and hydrocephalus present in 6 cases (27%). Patients arrived, on average, 50 min (range 23–78 min) from the time of symptom onset. Nearly 80% of the patients received a CT scan within 60 min of arrival to the ED. The median initial intracranial hematoma volume was 17.9 cm3 (interquartile ratio [IQR] 10.5–29.6 cm3). Emergent ventriculostomy in the first 24 h was performed in 1 patient. Three patients received factor VIIa in the ED. The average time from arrival in the ED to target MAP was 123 min (range 19 –297 min) (Table 2). The target of reducing the MAP to a level between 100 and 110 mm Hg within 120 min of arrival to the ED was obtained in 11 of the 22 cases (50%). Seventeen patients (77%) achieved the MAP target within 170 min, and 20 patients (91%) achieved the target within 200 min. Fourteen of the 22 patients (68%) required multiple agents to reach the target MAP. The most commonly used regimen included an initial bolus therapy with labetalol followed by a nicardipine drip. A total of 16 patients received continuous nicardipine (73%) and 12 patients received intermittent or continuous labetalol (55%). One patient had spontaneous regression of their MAP to the target range and did not require any antihypertensive therapy. The mean time to functional arterial line placement was 84 min (range 36 –160 min). The goal of placing a
Median (IQR) Radiologic data* Initial hematoma volume in cm3 Repeat hematoma volume in cm3 Neurologic data Initial GCS Initial NIHSS 24-hour GCS 24-hour NIHSS Discharge GCS Discharge NIHSS 3-month mRS
11.0 (7.5–19) 11.5 (9.1–16) 15 (11–15) 16 (10–18) 14 (12–15) 13 (12–21) 15 (15) 10 (6–11) 3 (2–4)
* One survivor did not have a repeat computed tomography scan. IQR ⫽ interquartile range; GCS ⫽ Glasgow Coma Scale score; NIHSS ⫽ National Institute of Health Stroke Scale score; mRS ⫽ modified Rankin score.
functional arterial line within 90 min of arrival was obtained in 12 of the 22 cases (55%). Eighteen patients (82%) received a functional arterial line within 110 min. Reasons for delay in achieving our target MAP and arterial line included: difficult intravenous (i.v.) access (4 patients), resistant hypertension (4 patients), difficulty in obtaining a definitive airway (3 patients), pharmacy delay in delivering antihypertensive medications (3 patients), and a delay in obtaining the CT scan (2 patients). The median initial hematoma volume, GCS and NIHSS scores, and 24-h neurological outcomes are outlined in Table 2. The median 3-month mRS was 5 (IQR 3– 6). The median initial hematoma volume of surviving patients was 11.0 cm3 (IQR 7.5–19 cm3) compared to 31.7 cm3 (IQR 22.3– 40.5 cm3) in non-survivors (p ⫽ 0.02). Surviving patients had a lower percentage of intraventricular extension (38%) compared with nonsurvivors (67%). The median initial GCS of surviving patients was 15 (IQR 11–15), compared to 6 (IQR 4 – 8) in non-survivors (p ⫽ 0.00). The median 24-h repeat hematoma volume for survivors was 11.5 cm3 (IQR 9.1–16 cm3) (p ⫽ 0.35 compared to initial hematoma volume) (Table 3). The 24-h median proportional hematoma growth in survivors was 4.5%. Significant 24-h intracranial hematoma expansion occurred in 2 patients (17%). Our protocol for BP management was well tolerated in 17 of the 22 cases (77%). Five patients required vasopressors in the first 24 h for hypotension after the antihypertensive therapy was weaned off (Table 4). Two additional patients experienced in-hospital adverse events. In one patient, pneumonia was recognized on hospital day 2. In the second patient, hydrocephalus requiring a ventriculostomy, transient renal insufficiency, and an ileus developed during
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Table 4. Timing of BP Control and Pressors for Non-Survivors (n ⴝ 9) Case
Goal MAP*
Vasopressors in the First 24 h (Time of Onset)†
Time of Death†
1 2 5‡ 6 12 13 17 21 22
1:50 1:40 0:36 2:50 2:24 4:57 3:07 0:19 1:34
No No Yes (2) Yes (16) Yes (14) No No Yes (14; stopped at 19) Yes (20)
26 60 24 21 25 29 103 44 36
* Time in hours:minutes from ED presentation. † Time in hours from ED presentation. ‡ This patient did not receive any antihypertensive agents. BP ⫽ blood pressure; MAP ⫽ mean arterial pressure.
the first week of hospitalization. Both of these patients survived. Nine patients died during hospitalization (in-hospital mortality 41%), with a majority occurring within 48 h of presentation. A tenth patient died 2 months after study enrollment. DISCUSSION In 2007, the American Stroke Association/American Heart Association updated their recommendations for BP control in patients with spontaneous ICH (1). A class IIb recommendation, based mainly on consensus opinion, concludes that “aggressive reduction” of the BP with continuous i.v. antihypertensive infusion should be considered in patients with MAP ⬎ 150 mm Hg and that a “modest reduction” of the BP with continuous or intermittent i.v. antihypertensive medication should be considered in patients with MAP ⬎ 130 mm Hg. These recommendations are based on a handful of studies that have shown a correlation between elevated initial BP in ICH and early intracranial hematoma expansion, neurologic morbidity, and mortality (3–9). Unlike acute ischemic stroke, pharmacologic regulation of MAP does not adversely affect regional cerebral blood flow or intracranial pressure in experimental models (15,16). The recent results of the INTERACT (Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage) trial support the notion that early BP control in patients with elevated BP and spontaneous ICH is warranted (17). In this prospective multicenter trial, patients were enrolled within 6 h of symptom onset and randomized to receive early intensive lowering of BP (target systolic BP 140 mm Hg) vs. standard care (target systolic BP 180 mm Hg). Patients in the intensive lowering of BP group had smaller volume of hematoma growth compared to pa-
tients receiving usual care (13.7% mean proportional hematoma growth in intensive care group compared to 36.3% in the standard care group; p ⫽ 0.04) at 24 h. A non-significant trend favoring mortality was seen in the intensive care group (overall mortality 10% vs. 13% in the standard care group). Several additional studies support the notion of early BP management in the treatment of spontaneous ICH in the ED. A retrospective chart review by Burke et al. found that patients with spontaneous ICH treated with antihypertensives in the first 6 h from initial presentation had a significant reduction in mortality compared to patients not treated in this time frame (18). A study by Qureshi et al. observed that patients with spontaneous ICH treated within 6 h of symptom onset were more likely to be functionally independent as judged by the mRS, compared to patients who were treated between 6 and 24 h (19). In our prospective series of 22 patients with spontaneous ICH presenting to a single institution, an ED protocol with aims to place an arterial line within 90 min of presentation and to reduce the MAP to 100 –110 mm Hg within 120 min of presentation was feasible in only 50% of patients. The average time from patient arrival in the ED to successful arterial line placement and target MAP was 84 min and 123 min, respectively. Although only 50% of our patients achieved a target MAP of 100 –110 mm Hg using our pre-specified goal of 120 min, over 90% of our patients reached this goal with an additional 80 min of therapy. A prior study by Koch et al. has shown that the MAP can be safely lowered to a level of ⬍ 110 mm Hg in patients with spontaneous ICH (20). The average time to target MAP in our study compares favorably to this study (123 min ⫾ 73 min compared to 163 min ⫾ 164 min in the Koch et al. study) (20). The majority of delays to achieving our target MAP and functional arterial line were due to delays in obtaining i.v. access, definitive airway control, and head CT scan, as well as delays in pharmacy delivery of antihypertensive medication. Our protocol was tolerated in over three-quarters of our patients per our study definition, as 5 patients required vasopressor therapy in the first 24 h. In all but one of these patients, vasopressors were started more than 14 h after initial ED presentation, long after the goal MAP was obtained. The one patient who required vasopressors within 2 h of presentation never received any antihypertensive medication (Table 4). Although all of these patients died, their mortality is unlikely to be related to rapid blood pressure lowering in the ED. It is more likely to be related to their larger hematoma volumes, higher rates of intraventricular extension, and lower GCS scores than the survivors, as these are the most important predictors of mortality from ICH (21).
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The observed mortality of 41%, with most deaths occurring the first 2 days, is consistent with prior studies (1,2,6,18,19,22). The 24-h median proportional hematoma growth in patients that survived was 4.5%. This impressive result is similar to results seen with intensive BP reduction group from the INTERACT trial (13.7% mean proportional hematoma growth compared to 36.3% in the standard care group, p ⫽ 0.04) (17). Neurological outcome in this group was also favorable, with a 3-month mRS of 3 (IQR 2– 4).
Limitations Given the observational nature of our study, we cannot conclude that aggressive BP control in the ED leads to reduced hematoma growth or improved clinical outcomes. Our design was to assess the feasibility and tolerability of achieving a MAP target of 100 –110 mm Hg in patients with spontaneous ICH who present to the ED with a MAP ⬎ 120 mm Hg. To this end, we have shown that these goals are possible in over 90% of patients in under 3½ hours. Although we successfully enrolled ⬎ 95% of eligible patients who presented in a 1-year study period, we were able to test our hypothesis in only 22 patients. This sample size of 22 patients is slightly smaller than those of two prospective studies by Qureshi et al. that enrolled 27 and 35 patients, respectively, and significantly smaller than the 404 patients enrolled in the INTERACT trail (17,19,22). Other limitations include interobserver bias, as emergency physicians obtained the initial GCS and NIHSS scores, and a neurologist or neurosurgeon obtained the subsequent scores. There was no assessment of interrater reliability between the different physicians. Finally, the physicians collecting the data and the neurologist reading the CT scan were not blinded to the study objectives.
CONCLUSION Our study shows that a protocol of early BP control in the ED for patients with spontaneous ICH is both feasible and safe. The observational nature of our study prevents us from definitively concluding that our protocol led to an improvement in hematoma volume or neurologic outcome compared to standard therapy. The results from the upcoming Antihypertensive Treatment of Acute Cerebral Hemorrhage trial and the follow-up to the Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage (INTERACT-2) trial should give us an evidence-
based answer to the question of whether aggressive BP control in patients with spontaneous ICH leads to better clinical outcome.
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ARTICLE SUMMARY 1. Why is this topic important? Hypertension is associated with early hematoma expansion, poor neurological outcome, and death in intracerebral hemorrhage. Recent studies have shown that early blood pressure control reduces hematoma growth and may decrease mortality. 2. What does this study attempt to show? This was a prospective observational trial testing the feasibility and tolerability of lowering mean arterial pressure to a range of 100 –110 mm Hg within 120 min of arrival in patients with spontaneous intracerebral hemorrhage in the Emergency Department (ED) setting. 3. What are the key findings? The average time for reaching our target mean arterial pressure was 123 min and for placing an arterial line was 84 min. The protocol was tolerated in 77% of patients, and our in-hospital mortality rate was 41%. 4. How is patient care impacted? If future trials demonstrate a clinical benefit of early blood pressure control in intracerebral hemorrhage, EDs could successfully implement similar protocols.