132 Clinical methods and pathophysiology
Role of catecholamines in acute hypertensive response: subarachnoid hemorrhage versus spontaneous intracerebral hemorrhage Joji Inamasu, Shigeta Moriya, Motoki Oheda, Mitsuhiro Hasegawa and Yuichi Hirose Background and objective Acute hypertensive response, defined as systolic blood pressure (SBP) 140 mmHg or more within 24 h of onset, is frequently observed in hemorrhagic stroke patients. Although catecholamine surge is pivotal in its pathogenesis, few studies have evaluated the relationship between admission SBP and plasma catecholamine levels. Patients and methods A prospective observational study was carried out to investigate potential differences in the acute hypertensive reaction between subarachnoid hemorrhage (SAH) and spontaneous intracerebral hemorrhage (SICH) by analyzing 200 SAH and 200 SICH patients. In each category, patients were quadrichotomized on the basis of their SBPs in emergency department: less than 140 mmHg, 140–184 mmHg, 185–219 mmHg, and 220 mmHg or more. The plasma catecholamine levels were compared among the four groups. Furthermore, multivariate regression analyses were carried out to identify variables correlated with hypertensive emergency (SBP ≥ 185 mmHg). Results In SAH patients, there was a proportional increase in norepinephrine levels relative to the graded SBPs, and norepinephrine levels in the 220 mmHg or more group were significantly higher than those in the less than 140 mmHg group (1596 ± 264 vs. 853 ± 124 pg/ml, P = 0.03).
Introduction An acute hypertensive response is the elevation of blood pressure (BP) above normal and premorbid values that occurs in stroke patients [1,2]. More practically, it is defined as systolic blood pressure (SBP) 140 mmHg or more found on two recordings taken 5 min apart within 24 h of symptom onset [1–3]. It is frequently observed in patients with hemorrhagic stroke – that is, subarachnoid hemorrhage (SAH) and spontaneous intracerebral hemorrhage (SICH), many of whom have chronic hypertension [4]. Among several pathomechanisms of the acute hypertensive response in hemorrhagic stroke patients, activation of the sympathetic nervous system, exemplified by elevated plasma catecholamine levels, may play a pivotal role [5,6]. However, few studies have evaluated the relationship between admission SBPs and plasma catecholamine levels in hemorrhagic stroke patients: it is possible that the acute hypertensive response in
By contrast, no proportional increase in norepinephrine levels to the graded SBPs was observed in SICH patients. Multivariate regression analyses showed that the initial Glasgow Coma Scale scores of 8 or less (odds ratio 2.251, 95% confidence interval 1.002–5.117) and plasma norepinephrine levels (odds ratio 1.002, 95% confidence interval 1.001–1.003) were correlated with hypertensive emergency in SAH patients. By contrast, none of the variables evaluated were correlated with hypertensive emergency in SICH patients. Conclusion An acute hypertensive response may be more complex, multifactorial, and less catecholamine dependent in SICH patients compared with SAH patients. Blood Press Monit 20:132–137 Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved. Blood Pressure Monitoring 2015, 20:132–137 Keywords: acute hypertensive reaction, catecholamine, hypertensive emergency, spontaneous intracerebral hemorrhage, subarachnoid hemorrhage Department of Neurosurgery, Fujita Health University Hospital, Toyoake, Japan Correspondence to Joji Inamasu, MD, PhD, FACS, Department of Neurosurgery, Fujita Health University Hospital, 1-98 Dengakugakubo, Toyoake 470-1192, Japan Tel: + 81 562 93 9253; fax: + 81 562 93 3118; e-mail: [email protected] Received 13 October 2014 Revised 24 November 2014 Accepted 8 December 2014
SAH and SICH patients may not be identical [6], and if this is the case, BPs in SAH and SICH patients may have to be managed differently. We carried out a prospective observational study to search for potential neurochemical differences in the acute hypertensive reaction between SAH and SICH by evaluating the relationship between SBPs measured in the emergency department (ED) and plasma catecholamine levels in 200 SAH and 200 SICH patients consecutively. SBP of 185 mmHg or more has been defined as hypertensive emergency for which immediate BP reduction with intravenous antihypertensive has been recommended in recent guidelines [7–9]. We also carried out a multivariate logistic regression analysis to identify clinical variables correlated with hypertensive emergency both in SAH and in SICH patients to evaluate whether or not their roles in the acute hypertensive response are the same.
1359-5237 Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
Copyright © 2015 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
DOI: 10.1097/MBP.0000000000000106
Catecholamines and hemorrhagic stroke Inamasu et al. 133
Patients and methods Patients
This is a single-center prospective observational study. The study protocol was approved by our institutional internal review board, and informed consent was obtained from patients’ surrogates. The 200 consecutive SAH patients were admitted between October 2009 and December 2013. The 200 consecutive SICH patients were admitted between May 2011 and December 2013. The blood samples for the plasma catecholamine (norepinephrine/epinephrine) measurements were collected shortly after arrival to our ED. Plasma catecholamine levels were measured by high-performance liquid chromatography (SRL Inc., Tokyo, Japan). We excluded hemorrhagic stroke patients who arrived at our institution later than 6 h of symptom onset. Similarly, patients whose acute hypertensive reaction had been treated at referring hospitals (n = 18) and those who had received intravenous vasopressors before sample collection for severe hypotension (n = 7) were excluded. Clinical management
Upon the patients’ arrival to our ED, their BPs were measured repeatedly using automated BP monitors with a 5-min interval, and those with marked hypertension received continuous intravenous administration of nicardipine, initiated from 5 mg/h immediately after imaging studies, to maintain SBP from 140 mmHg or less to 160 mmHg [8,9]. Only BP values before the initiation of intravenous nicardipine were used for analysis. In each hemorrhagic stroke category, patients were quadrichotomized on the basis of their admission SBP: less than 140 mmHg, 140–184 mmHg, 185–219 mmHg, and 220 mmHg or more. This classification was based on a study by Qureshi et al. [4]. The average of the two highest SBP values was used for analysis to be compatible with definition of the acute hypertensive response [1–3]. Plasma catecholamine levels were compared among the four groups in each hemorrhagic stroke category. The relationship between the initial Glasgow Coma Scale (GCS) scores and plasma norepinephrine levels was also evaluated. Furthermore, the correlation between norepinephrine and epinephrine levels was evaluated with linear regression analysis. Multivariate logistic regression analysis
Clinical factors evaluated both in SAH and in SICH patients were age, sex, admission GCS score of 8 or less, underlying comorbidities/risk factors (chronic hypertension, diabetes, alcohol use, and tobacco use), the presence of concomitant intraventricular hemorrhage, and plasma epinephrine and norepinephrine levels. In SAH patients, the location of the ruptured aneurysm (anterior vs. posterior circulation aneurysms) was added as a variable. In SICH patients, the location of hematoma and estimated hematoma volume were added as variables. Hematomas were either classified as deep-seated
(brainstem, cerebellar, putamen, and thalamus) or subcortical. The hematoma volume was calculated using the ABC/2 method [10,11]. Statistical analysis
The χ2-test was used for comparison of categorical variables. For numerical variables, Student’s t-test and oneway analysis of variance with Bonferroni correction were used for two-group and four-group comparison, respectively. JMP (SAS Institute, Cary, North Carolina, USA) and Prism (GraphPad Software, La Jolla, California, USA) were the softwares used for analysis. Numerical data are expressed as mean ± SD; and P-value less than 0.05 was considered statistically significant.
Results Demographics
The 200 SAH patients included 64 men and 136 women (mean age 61.9 ± 15.1 years). The 200 SICH patients included 131 men and 69 women (mean age 67.4 ± 12.2 years). The SAH group included significantly more women (P < 0.001) and younger patients (P < 0.001). The mean initial GCS scores were similar between the two groups (11.2 ± 4.3 vs. 11.3 ± 3.7, P = 0.63). However, the frequencies of both chronic hypertension and diabetes were significantly higher in the SICH group (Table 1). There were no significant differences in the frequencies of alcohol/tobacco use and plasma total cholesterol levels on admission between the two groups (Table 1). Frequency and degree of acute hypertensive reaction
On the basis of their admission SBPs, the 200 SAH patients were classified into four groups: less than 140 mmHg (n = 44), 140–184 mmHg (n = 92), 185–219 mmHg (n = 36), Demographics of 200 subarachnoid hemorrhage and 200 spontaneous intracerebral hemorrhage patients
Table 1
SAH (n = 200) Age (years) Male : female Initial GCS scores Location of SICHs/ aneurysms WFNS SAH grade Chronic hypertension [n (%)] Diabetics [n (%)] Alcohol use [n (%)] Tobacco use [n (%)] Total cholesterol levels (mg/dl)
61.9 ± 15.1 64 : 136 11.2 ± 4.3 ACA 18, AComA 53, BA 9, ICA 60, MCA 46, VA 14 I/II 71, III 42, IV 32, V 55 103 (51.5) 23 (11.5) 85 (42.5) 73 (37.5) 190.8 ± 40.7
SICH (n = 200) 67.4 ± 12.2 131 : 69 11.3 ± 3.7 Bs 13, Cb 19, Pu 93, Sub 23, Th 62 NA 165 (82.5) 44 (22.0) 85 (42.5) 68 (34.0) 189.2 ± 41.2
P-value < 0.001* < 0.001* 0.65 NA
NA < 0.001* 0.005* 1.00 0.60 0.76
ACA, anterior cerebral artery; AComA, anterior communicating artery; BA, basilar artery; Bs, brainstem; Cb, cerebellar; GCS, Glasgow Coma Scale; ICA, internal carotid artery; MCA, middle cerebral artery; NA, not applicable; Pu, putamen; SAH, subarachnoid hemorrhage; SICH, spontaneous intracerebral hemorrhage; Sub, subcortex; Th, thalamus; VA, vertebral artery; WFNS, World Federation of Neurosurgical Societies. *Statistically significant.
Copyright © 2015 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
134 Blood Pressure Monitoring 2015, Vol 20 No 3
Fig. 1
Correlation between norepinephrine and epinephrine in hemorrhagic stroke
P < 0.001 100% >220mmHg 185−220 mmHg 140−184mmHg
Role of catecholamines in acute hypertensive response: subarachnoid hemorrhage versus spontaneous intracerebral hemorrhage Joji Inamasu, Shigeta Moriya, Motoki Oheda, Mitsuhiro Hasegawa and Yuichi Hirose Background and objective Acute hypertensive response, defined as systolic blood pressure (SBP) 140 mmHg or more within 24 h of onset, is frequently observed in hemorrhagic stroke patients. Although catecholamine surge is pivotal in its pathogenesis, few studies have evaluated the relationship between admission SBP and plasma catecholamine levels. Patients and methods A prospective observational study was carried out to investigate potential differences in the acute hypertensive reaction between subarachnoid hemorrhage (SAH) and spontaneous intracerebral hemorrhage (SICH) by analyzing 200 SAH and 200 SICH patients. In each category, patients were quadrichotomized on the basis of their SBPs in emergency department: less than 140 mmHg, 140–184 mmHg, 185–219 mmHg, and 220 mmHg or more. The plasma catecholamine levels were compared among the four groups. Furthermore, multivariate regression analyses were carried out to identify variables correlated with hypertensive emergency (SBP ≥ 185 mmHg). Results In SAH patients, there was a proportional increase in norepinephrine levels relative to the graded SBPs, and norepinephrine levels in the 220 mmHg or more group were significantly higher than those in the less than 140 mmHg group (1596 ± 264 vs. 853 ± 124 pg/ml, P = 0.03).
Introduction An acute hypertensive response is the elevation of blood pressure (BP) above normal and premorbid values that occurs in stroke patients [1,2]. More practically, it is defined as systolic blood pressure (SBP) 140 mmHg or more found on two recordings taken 5 min apart within 24 h of symptom onset [1–3]. It is frequently observed in patients with hemorrhagic stroke – that is, subarachnoid hemorrhage (SAH) and spontaneous intracerebral hemorrhage (SICH), many of whom have chronic hypertension [4]. Among several pathomechanisms of the acute hypertensive response in hemorrhagic stroke patients, activation of the sympathetic nervous system, exemplified by elevated plasma catecholamine levels, may play a pivotal role [5,6]. However, few studies have evaluated the relationship between admission SBPs and plasma catecholamine levels in hemorrhagic stroke patients: it is possible that the acute hypertensive response in
By contrast, no proportional increase in norepinephrine levels to the graded SBPs was observed in SICH patients. Multivariate regression analyses showed that the initial Glasgow Coma Scale scores of 8 or less (odds ratio 2.251, 95% confidence interval 1.002–5.117) and plasma norepinephrine levels (odds ratio 1.002, 95% confidence interval 1.001–1.003) were correlated with hypertensive emergency in SAH patients. By contrast, none of the variables evaluated were correlated with hypertensive emergency in SICH patients. Conclusion An acute hypertensive response may be more complex, multifactorial, and less catecholamine dependent in SICH patients compared with SAH patients. Blood Press Monit 20:132–137 Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved. Blood Pressure Monitoring 2015, 20:132–137 Keywords: acute hypertensive reaction, catecholamine, hypertensive emergency, spontaneous intracerebral hemorrhage, subarachnoid hemorrhage Department of Neurosurgery, Fujita Health University Hospital, Toyoake, Japan Correspondence to Joji Inamasu, MD, PhD, FACS, Department of Neurosurgery, Fujita Health University Hospital, 1-98 Dengakugakubo, Toyoake 470-1192, Japan Tel: + 81 562 93 9253; fax: + 81 562 93 3118; e-mail: [email protected] Received 13 October 2014 Revised 24 November 2014 Accepted 8 December 2014
SAH and SICH patients may not be identical [6], and if this is the case, BPs in SAH and SICH patients may have to be managed differently. We carried out a prospective observational study to search for potential neurochemical differences in the acute hypertensive reaction between SAH and SICH by evaluating the relationship between SBPs measured in the emergency department (ED) and plasma catecholamine levels in 200 SAH and 200 SICH patients consecutively. SBP of 185 mmHg or more has been defined as hypertensive emergency for which immediate BP reduction with intravenous antihypertensive has been recommended in recent guidelines [7–9]. We also carried out a multivariate logistic regression analysis to identify clinical variables correlated with hypertensive emergency both in SAH and in SICH patients to evaluate whether or not their roles in the acute hypertensive response are the same.
1359-5237 Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
Copyright © 2015 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
DOI: 10.1097/MBP.0000000000000106
Catecholamines and hemorrhagic stroke Inamasu et al. 133
Patients and methods Patients
This is a single-center prospective observational study. The study protocol was approved by our institutional internal review board, and informed consent was obtained from patients’ surrogates. The 200 consecutive SAH patients were admitted between October 2009 and December 2013. The 200 consecutive SICH patients were admitted between May 2011 and December 2013. The blood samples for the plasma catecholamine (norepinephrine/epinephrine) measurements were collected shortly after arrival to our ED. Plasma catecholamine levels were measured by high-performance liquid chromatography (SRL Inc., Tokyo, Japan). We excluded hemorrhagic stroke patients who arrived at our institution later than 6 h of symptom onset. Similarly, patients whose acute hypertensive reaction had been treated at referring hospitals (n = 18) and those who had received intravenous vasopressors before sample collection for severe hypotension (n = 7) were excluded. Clinical management
Upon the patients’ arrival to our ED, their BPs were measured repeatedly using automated BP monitors with a 5-min interval, and those with marked hypertension received continuous intravenous administration of nicardipine, initiated from 5 mg/h immediately after imaging studies, to maintain SBP from 140 mmHg or less to 160 mmHg [8,9]. Only BP values before the initiation of intravenous nicardipine were used for analysis. In each hemorrhagic stroke category, patients were quadrichotomized on the basis of their admission SBP: less than 140 mmHg, 140–184 mmHg, 185–219 mmHg, and 220 mmHg or more. This classification was based on a study by Qureshi et al. [4]. The average of the two highest SBP values was used for analysis to be compatible with definition of the acute hypertensive response [1–3]. Plasma catecholamine levels were compared among the four groups in each hemorrhagic stroke category. The relationship between the initial Glasgow Coma Scale (GCS) scores and plasma norepinephrine levels was also evaluated. Furthermore, the correlation between norepinephrine and epinephrine levels was evaluated with linear regression analysis. Multivariate logistic regression analysis
Clinical factors evaluated both in SAH and in SICH patients were age, sex, admission GCS score of 8 or less, underlying comorbidities/risk factors (chronic hypertension, diabetes, alcohol use, and tobacco use), the presence of concomitant intraventricular hemorrhage, and plasma epinephrine and norepinephrine levels. In SAH patients, the location of the ruptured aneurysm (anterior vs. posterior circulation aneurysms) was added as a variable. In SICH patients, the location of hematoma and estimated hematoma volume were added as variables. Hematomas were either classified as deep-seated
(brainstem, cerebellar, putamen, and thalamus) or subcortical. The hematoma volume was calculated using the ABC/2 method [10,11]. Statistical analysis
The χ2-test was used for comparison of categorical variables. For numerical variables, Student’s t-test and oneway analysis of variance with Bonferroni correction were used for two-group and four-group comparison, respectively. JMP (SAS Institute, Cary, North Carolina, USA) and Prism (GraphPad Software, La Jolla, California, USA) were the softwares used for analysis. Numerical data are expressed as mean ± SD; and P-value less than 0.05 was considered statistically significant.
Results Demographics
The 200 SAH patients included 64 men and 136 women (mean age 61.9 ± 15.1 years). The 200 SICH patients included 131 men and 69 women (mean age 67.4 ± 12.2 years). The SAH group included significantly more women (P < 0.001) and younger patients (P < 0.001). The mean initial GCS scores were similar between the two groups (11.2 ± 4.3 vs. 11.3 ± 3.7, P = 0.63). However, the frequencies of both chronic hypertension and diabetes were significantly higher in the SICH group (Table 1). There were no significant differences in the frequencies of alcohol/tobacco use and plasma total cholesterol levels on admission between the two groups (Table 1). Frequency and degree of acute hypertensive reaction
On the basis of their admission SBPs, the 200 SAH patients were classified into four groups: less than 140 mmHg (n = 44), 140–184 mmHg (n = 92), 185–219 mmHg (n = 36), Demographics of 200 subarachnoid hemorrhage and 200 spontaneous intracerebral hemorrhage patients
Table 1
SAH (n = 200) Age (years) Male : female Initial GCS scores Location of SICHs/ aneurysms WFNS SAH grade Chronic hypertension [n (%)] Diabetics [n (%)] Alcohol use [n (%)] Tobacco use [n (%)] Total cholesterol levels (mg/dl)
61.9 ± 15.1 64 : 136 11.2 ± 4.3 ACA 18, AComA 53, BA 9, ICA 60, MCA 46, VA 14 I/II 71, III 42, IV 32, V 55 103 (51.5) 23 (11.5) 85 (42.5) 73 (37.5) 190.8 ± 40.7
SICH (n = 200) 67.4 ± 12.2 131 : 69 11.3 ± 3.7 Bs 13, Cb 19, Pu 93, Sub 23, Th 62 NA 165 (82.5) 44 (22.0) 85 (42.5) 68 (34.0) 189.2 ± 41.2
P-value < 0.001* < 0.001* 0.65 NA
NA < 0.001* 0.005* 1.00 0.60 0.76
ACA, anterior cerebral artery; AComA, anterior communicating artery; BA, basilar artery; Bs, brainstem; Cb, cerebellar; GCS, Glasgow Coma Scale; ICA, internal carotid artery; MCA, middle cerebral artery; NA, not applicable; Pu, putamen; SAH, subarachnoid hemorrhage; SICH, spontaneous intracerebral hemorrhage; Sub, subcortex; Th, thalamus; VA, vertebral artery; WFNS, World Federation of Neurosurgical Societies. *Statistically significant.
Copyright © 2015 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
134 Blood Pressure Monitoring 2015, Vol 20 No 3
Fig. 1
Correlation between norepinephrine and epinephrine in hemorrhagic stroke
P < 0.001 100% >220mmHg 185−220 mmHg 140−184mmHg
