Increase in hematoma volume (HV) in the brain after intracerebral hemorrhage (ICH) is a major cause of worsening clinical condition, and is an independent predictor for mortality and outcome. Our goals were to evaluate the relationship between subclinical, clinical factors to change intracerebral HV in acute supratentorial hemorrhage in first 72 hours after onset.
Journal of military pharmaco-medicine 7-2013 EVALUATION OF RELATIONSHIP BETWEEN TESTS, CLINICAL FACTORS TO CHANGE INTRACEREBRAL Hematoma Volume IN ACUTE SUPRATENTORIAL HEMORRHAGE Dinh Vinh Quang*; Nguyen Van Chuong** summary Increase in hematoma volume (HV) in the brain after intracerebral hemorrhage (ICH) is a major cause of worsening clinical condition, and is an independent predictor for mortality and outcome Our goals were to evaluate the relationship between subclinical, clinical factors to change intracerebral HV in acute supratentorial hemorrhage in first 72 hours after onset Descriptive, prospective analysis of 188 acute supratentorial hemorrhage patients associated with hypertension at admission, admitted within six hours after onset, from 2010 to 2013 Results: The average age was 58.2, including 128 males (68%) and 60 females (32%) Univariate analysis showed that important factors related to increased HV were: (1) Glasgow on admission, (2) NIHSS on admission, (3) Rankin at admission, (4) SBP at admission, (5) Hematoma volume, (6) Shape of hematoma, (7) Spot sign, (8) WBC, and (9) Glycemie Multivariate analysis showed that two independent prognostic factors associated with increasing HV were: (1) The shape of the hematoma is irregular on CT, and (2) Spot sign on CTA * Key words: Acute supratentorial hemorrhage; Subclinical, clinical factors INTRODUCTION Stroke, one of the causes of death in neurological diseases, or prolonged sequelae and disabilities, is a common disorder Intracerebral hemorrhage (ICH) accounted for 15 to 20% of stroke, causing death or severe disability more than cerebral infarction [3] In ICH appeared, risk factors, hypertension and cerebral amyloid angiopathy accounted for 78-88% [2] When ICH appears, there are some factors affecting to clinical status of the patient (PT) An increase in HV in the brain after ICH is a major cause worsening clinical condition and is an independent predictor for mortality and outcome [8] Identifying the factors that increase HV(HV) after ICH is important in the treatment and prognosis of ICH patients In the acute ICH phase, if hypertension uncontrolled can increase the risk of continuous bleeding or re-bleeding, increased HV For the treatment and better care of ICH patients in the early hours, we performed this study, aiming to: Evaluate the relationship between tests, clinical factors to change intracerebral HV in acute supratentorial hemorrhage in first 72 hours after onset Subjects and Methods Subjects Patients with acute supratentorial hemorrhage associated with hypertension, admission before * 115 Hospital ** 103 Hospital Address correspondence to Dinh Vinh Quang: 115 Hospital E.mail: quanghung115@yahoo.com.vn Journal of military pharmaco-medicine 7-2013 six hours after onset, treated at Department of Cerebral-Vascular Pathology, 115 People Hospital from - 2011 to - 2013 agreed with enrollment in the study Inclusion criteria will be included in the study * Inclusion criteria: ICH is the first acute supratentorial hemorrhage (STH) associated with hypertension at admission, admitted within six hours after onset Brain images on computerized tomography (CT) help diagnose supratentorial hemorrhage Hypertension diagnostic criteria (the JNC VII): The systolic blood pressure (SBP) higher than 140 and/or diastolic blood pressure (DBP) higher than 90 mmHg * Exclusion criteria: - Supratentorial hemorrhage (STH) due to aneurysm rupture, arteriovenous malformations, moyamoya disease, by using anticoagulants or anti-platelet drugs -.STH with blood intraventricul ar (intraventricular hemorrhage) - Patients died before the second CT.Scan shot - STH transformation of cerebral infarction - Renal failure, creatinine ≥ 1.7 mg/dl - A history of allergy to contrast drugs Research methodology Study design: descriptive, prospective analysis, univariate regression and multivariate Data collection - The clinical data: age, gender, time from onset to hospitalization, history of hypertension, diabetes, heart disease, liver disease, smoking, drinking, time of onset, the symptoms onset + BP, consciousness at admission, paralysis of cranial nerve VII, strength of the arms and legs paralyzed + Glasgow, NIHSS, Rankin at admission and 72 hours after onset + BP at hour, then BP measurement every hours to 72 hours after stroke - Tests data: + Take unenhanced CT at admission + Blood tests: Red blood cells (RBC), hemoglobin (Hb), hematocrit (Hct), white blood cells (WBC), platelet count (PTC), glycemie, total cholesterol, LDL-cholesterol, HDL-cholesterol, triglyceride, liver function tests (AST, ALT-aspartate aminotransferase, alanine aminotransferase), renal function (bun, creatinine), PT (prothrombin time), APTT (activated partial thromboplastin time), fibrinogen, INR + Brain CT-angiography (CTA) in the first 24 hours after onset + Take the second unenhanced CT as clinical status worsen (Glasgow score decreased from two points or more) or 72 hours after stroke Assessment criterial - STH status of patients after 72 hours was evaluated in two groups: blood volume without increase and increase (enlargement) HV in the brain increases under Kazui [16] as V2 - V1 ≥ 12.5 cm3 or V2/V1 ≥ 1.4, where V1, V2 respectively HV on brain CT-scan 1st and nd time - HV calculated by Kothari ,s formular (or Broderich): V = (A x B x C)/2 Where A, B, C are the largest three diameter perpendicular to each other in three dimensions of the hematoma - Find the factors affecting changes HV of STH in the first 72 hours after admission by means of univariate regression analysis - After univariate analysis, the significant important variables in univariate analysis will be included in a multivariate regression analysis Journal of military pharmaco-medicine 7-2013 to find the binary logistic variable prognostic value after adjustment by other variables and evaluate odds ratio OR (odds ratio) Results and discussion General characteristics of the study group - Age: mean age: 58.29, similar to the common age for stroke in general - Gender: 188 patients, including 128 males (68.08%) and 60 females (31.91%), ratio between men and women was 2:1 - The onset period and admission: average 4.03 hours, of which, 10 patients (5.3%) in the first hour, 76 patients (40.4%) in hours The risk factors the two groups with p value of 0.78, 1.00, 1.00, 1.00, 0.75, 0.59 respectively The clinical factors and test - Symptoms at onset: + There is no difference in symptoms at onset such as dizziness, headache, vomiting, seizures, speech disorders between two groups of increase and non-increase HV with p value of 0.75, 0, 45, 0.059, 1.00, and 0.13 respectively + Rate enlargement HV in patients with paralysis on the left (70.83%) was significantly higher than the right side paralyzed patients (29.17%), this difference was statistically significant with p = 0.043 + Consciousness: Enlargement HV rate in patients with glasgow 13 - 15, - 12, ≤ score at admission were 72%, 22% and 6% respectively It was noted that enlargement HV rate was different between groups of conscious disorder at admission (p = 0.04) Figure 1: The risk factors of stroke patients with STH Patients with history of hypertension are times as many as those without history of hypertension In the study group, most patients had no history of liver disease, heart disease and stroke before ICH In comparing the two groups of increase and non-increase HV in patients with history of non-and hypertension, diabetes, heart disease, liver disease, smoking, alcohol drinking, we found no difference between + There is a difference in scores of neurological symptoms at admission assessed by Glasgow, NIHSS, mRS scales in both groups of increase and non-increase HV This difference is statistically significant with a p value of 0.02, 0.02, and 0.03 respectively Table 1: Comparison of neurological scales between the two groups of increase and non-increase in HV At non admission increase Glasgow increase p value 15 13.5 0.02 NIHSS 12.3 15.5 0.02 Rankin 3.8 4.0 0.03 Journal of military pharmaco-medicine 7-2013 - Blood pressure: When comparing the mean blood pressure between the groups with and without increased HV, we realized significant differences in blood pressure between the two groups, the SBP, DBP and MAP Table 2: Comparison of blood pressure between the two groups increased and did not increase hematoma volume BP (mmHg) Nonincrease increase p value Average SBP/72h 137 146 0.0016 Average DBP/72h 80 84 0.0001 Figure 2: V1, V2 is HV on 1st and 2nd CT taken at admission and nd time Average MAP/72h 99 105 0.0003 (Sources: CT-scans of patient in this study) In the first 72 hours, the group increased HV had average SBP > 140 mmHg compared with the group of non-increase HV (average SBP < 140 mmHg), this difference was statistically significant (p = 0.0016) In a study by Fujii [10], the results showed enlargement HV rate increased significantly with higher values SBP after admission, the rate of HV increase in patients with SBP < 145 mm Hg, 145 - 160 mm Hg, > 160 - 175 mmHg, and ≥ 175 mmHg, 6.5%, 13.0%, 14.1%, and 21.7% respectively - Characteristics of hematoma on CT: + HV on 2nd CT compared with 1st CT: Figure 3: HV on 1st and nd CT of patients In 188 patients, we recorded 24 patients (12.77%) with an increase in HV (enlargement cerebral hemorrhage), 164 patients (88.23%) without an increase when compared to HV on CT.Scan 2nd to 1st, similar to the study by Fujii et al: 14.0% and other studies : increased HV rate of 3% [5], 7% [9], 14% [10] Time blood continues to flow after ICH undetermined Bleeding time in ICH is usually supposed to end from a few minutes to an hour Fujii et al [11] studied 419 patients Journal of military pharmaco-medicine 7-2013 with ICH, taken CT-scan within the first 24 hours after onset and the second within 24 hours of admission, 60 patients (14.3%) on the 2nd CT increase HV The authors noted that increased HV rate decreases over time Some other studies showed that blood flow may still continue and last longer than hours after onset [7, 9] - Location of hematoma on brain CT: There were significant differences in the rate of hematoma location between groups divided according to location as follows: 82.98% basal ganglia, 2.66% capsule, 9.04% thalamus, 5.32% brain lobes Over 85% of patients had putamen hemorrhage Compared with other studies, in a study by Nguyen Minh Hien (1995) [1], the rate of putamen hemorrhage was 48%, Nguyen Van Dang (1997) was 50%, Duc Kiet Hoang with rate of the capsule-striatum hemorrhage was 47.1%, Nguyen Lien Huong: 38.6% In a study by Matthew L.Flaherty (2005) in Kentucky-North America, the rate of capsule - putamen hemorrhage was 49% Although the significant difference in hematoma location between groups of patient was classified according to location as above, there was no significant difference in enlargement rate between the groups hematoma location in the lobes, basal ganglia, capsule and thalamus (p = 0.26) This result was similar to the study by Fujii [10] - Shape of hematoma on the brain CT: Ratio of enlargement hematoma in group of irregular hematoma shape (10/22) was significant higher than group of regular hematoma shape (14/166) (p = 0.000) This result is similar to the study by Fujii [10] Figure 4: Shape of hematoma on the brain CT (Source: CT at admission and second of patients in this study) - HV on the first CT: The relationship between increased HV and HV was shown examining in 188 STH patients HV increased in 20.83% of patients with HV small (< 15 cm 3), 29.17% in those with moderate HV (15 - 29 cm 3), 16.67% in those with big hematoma (30 - 45 cm 3), and 33.33% in those with large hematoma (> 45 cm 3) Enlargement HV rate increased significantly with an increase in blood volume in the series first CT This result is similar to the study by Fujii [10] - Time CTA: Ratio of enlargement hematoma in group of patients with time from onset to take the CTA < hours, - 12 hours before, 12 - before Journal of military pharmaco-medicine 7-2013 18 hours, 18 - 24 hours: 34.78%, 30.43%, 0.0% and 34.78%, respectively Ratio of enlargement hematoma in groups with different times taken CTA did not differ statistically significant (p = 0.12) - Spot sign: Image of contrast drug extravasation (spot sign) on brain CTA: After ICH, the contrast brain CT scan and/or CT.Angiography (CTA) in the early hours, we can see image of contrast drug extravasation and left in hematoma, the predicted sign blood still continues to flow, which can identify the risk of increased HV [6] The results of our study revealed increased HV in 18 of 168 patients without spot sign (75%), of 20 patients with a spot sign (25%) When univariate analysis, this difference is statistically significant (p = 0.005) The result is similar to the study by Ryan Wada (p = 0.0001), and E Josser Delgado Almandoz (p < 0.0001) Figure 5: Spot sign on the CTA (Source: CT at admission, CTA and CT 2nd times of patient in this study) - The test parameters: Table 3: Comparison of the indices between the two groups of increase and nonincrease in HV Non-increase increase p value RBC 4.66122 4.762083 0.4168 Hct 41.21159 41.87083 0.4934 Hb 13.97744 14.52083 0.1239 WBC 10.02238 11.71292 0.0337 Platelets 244.8659 244.4583 0.9794 AST 41.91463 43.08333 0.8878 ALT 36.29878 32.91667 0.6929 PT 13.09146 13.24583 0.6800 Journal of military pharmaco-medicine 7-2013 (1) (2) (3) (4) aPTT 27.94207 26.74167 0.3793 INR 1.168963 1.021667 0.7391 Fibrinogen 3.117805 2.871667 0.1898 Glycemie 120.3902 146.25 0.0275 BUN 13.89634 10.57083 0.0542 Creatinine 0.9161585 0.8395833 0.2799 Total cholesterol 200.4207 196.1667 0.6834 LDL 113.5671 110.0833 0.6201 HDL 46.10429 48.04167 0.4055 TGR 46.10429 48.04167 0.4055 White blood cell count and glycemie levels in patients with increased HV was higher in patients without increased HV, this difference is statistically significant (p = 0.033) and 0.027 Similar results in the study of Kazui and colleagues found that glycemie at admission ≥ 141 mg/dl is a risk factor of increasing HV According to Fisher CM (1971), glycemie at admission ≥ 200 mg/dl will aggrevate the clinical condition of the ICH patient in the acute phase [4] Univariate analysis above showed that the presence of 14 factors related to increased HV, of which, were important factors related to increased HV such as: (1) Glasgow at admission, (2) NIHSS at admission, (3) Rankin at admission, (4) SBP at admission, (5) HV, (6) shape of hematoma, (7) spot sign, (8) WBC and (9) glycemie - Multivariate analysis of factors affecting increase HV: Our multivariate regression analysis presented independent predictors of increased HV Univariate analysis also showed the presence of 14 factors related to increased HV, which we picked out key factors related to increased HV for inclusion in multivariate analysis with the dependent variable of increased HV Table 4: Multivariate analysis of factors affecting the increase HV OR p CI 95% 1.07 0.69 0.7403871 1.568776 NIHSS at admission 0.99 0.91 0.8507506 1.155765 Rankin at admission 4.75 0.18 0.4700964 48.11052 SBP at admission 1.08 0.41 0.8942917 1.314039 HV on 1st CT 1.01 1.02 0.9961331 1.044145 Shape of hematoma 0.19 0.005 0.0606533 0.6088062 Spot sign 2.41 0.04 1.023745 WBC 1.05 0.43 0.9182124 1.217977 Glycemie 1.00 0.08 0.9991597 1.014602 Glasgow at admission 5.692294 Journal of military pharmaco-medicine 7-2013 Results of multivariate analysis showed that two independent prognostic factors with increasing HV are: (1) the shape of the hematoma is irregular on CT (OR = 0.19, p = 0.005), and (2) Spot sign on CTA (OR = 2.41, p = 0.044) In this study, we identified two prognostic factors that independently increased HV are: (1) the shape of the hematoma is irregular on CT, and (2) Spot sign on CTA Compared with previous studies, those by Fujii [10], in addition to the shape of the hematoma is irregular on CT factor, this author also recorded other factors with independent prognostic HV increase including: (1) time from onset to admission early (before 6h), (2) the amount of alcohol consumed during the day, (3) consciousness disorders at admission, and (4) low fibrinogen levels As for spot sign, our results are similar to two studies by Ryan Wada and Josser E, Delgado Almandoz that signals spot is an independent prognostic factor for the increase in HV Conclusion Through a prospective study of 188 STH patients with hypertension at admission, we draw some conclusions: - Average age: 58 years old, men were twice as many as women - The time between stroke onset and hospitalization was hour on average, only 5.3% during the first hour, 40.4% at hours - Average HV on nd CT was 26.54 cm3, 1st CT was 22.35 cm 89.36% of patients had regular hematoma shape, 10.64% had irregular hematoma shape, over 85% of STH located in the basal ganglia and capsule - 10.64% of STH patients had the spot sign on CTA - Rate of increased HV on 2nd CT after 72 hours was 12.77% when compared with 1st CT - Univariate analysis showed that important factors related to increased HV are: (1) Glasgow at admission, (2) NIHSS at admission, (3) Rankin at admission, (4) SBP at admission, (5) hematoma volume, (6) shape of hematoma, (7) spot sign, (8) WBC and (9) glycemie - Multivariate analysis showed that two independent prognostic factors related to an increase in HV: (1) the shape of the hematoma was irregular on CT (OR = 0.19, p = 0.005) and (2) spot sign on CTA (OR = 2.41, p = 0.044) REFERENCES Nguyen Minh Hien Some of clinical features and Siriraj diagnostic scale in distinguish supratentorial cerebral infarction Journal of Neurology 2003, 4, pp.52-55 Vu Anh Nhi Thần kinh học Department of Neurology Medical University Hochiminh City Medical Publisher 2003 Anderson CS, Jamrozik KD, Broadhurst RJ, Stewart-Wynne EG Predicting survival for year among different subtypes of stroke: results from the Perth Community Stroke Group Stroke 1994, 25, pp.1935-1944 Badjatia N, Rosand J Intracerebral hemorrhage The Neurologist 2005, 11 (6), pp.311-324 Journal of military pharmaco-medicine 7-2013 Bae HG, Lee KS, Yun IG, et al Rapid expansion of hypertensive intracerebral hemorrhage Neurosergery 1992, 31 (1), pp.35-41 Becker KJ, Baxter AB, Bybee HM, Tirschwell DL, Abouelsaad T, Cohen WA Extravasation of radiographic contrast is an independent predictor of death in primary intracerebral hemorrhage Stroke 1999, 30, pp.2025-2032 Chen ST, Chen SD, Hsu CY, Hogan EL Progression of hypertensive intracerebral hemorrhage Neurology 1989, 39, pp.1509-1514 Davis SM, Broderick J, Hennerici M, Brun NC, Diringer MN, Mayer SA, Begtrup K, Steiner T Activated recombinant factor VII intracerebral hemorrhage trial investigators Hematoma growth is a determinant of mortality and poor outcome after intracerebral hemorrhage Neurology 2006, 66, pp.1175-1181 Fehr MA, Anderson DC Incidence of progression or rebleeding in hypertensive intracerebral hemorrhage Stroke Cerebrovascular Dis 1991, 1, pp.111-116 10 TR Fujii Y, Takeuchi S, Minakawa T, Sasaki O Multivariate analysis of hematoma enlargement in spontaneous intracerebral hemorrhage Stroke 1998, 29, pp.1160-1166 Journal of military pharmaco-medicine 7-2013 ... similar to the study by Fujii [10] - Shape of hematoma on the brain CT: Ratio of enlargement hematoma in group of irregular hematoma shape (10/22) was significant higher than group of regular hematoma. .. the presence of 14 factors related to increased HV, which we picked out key factors related to increased HV for inclusion in multivariate analysis with the dependent variable of increased HV... [10], in addition to the shape of the hematoma is irregular on CT factor, this author also recorded other factors with independent prognostic HV increase including: (1) time from onset to admission