Defining Hypotension in Patients with Severe Traumatic Brain Injury

Original Article

Defining Hypotension in Patients with Severe Traumatic Brain Injury Keita Shibahashi1, Kazuhiro Sugiyama1, Yoshihiro Okura1, Jun Tomio2, Hidenori Hoda1, Yuichi Hamabe1

BACKGROUND: Hypotension, a risk factor for increased mortality following traumatic brain injury (TBI), is traditionally defined as systolic blood pressure (SBP) <90 mm Hg. We aimed to redefine hypotension and determine its optimal threshold in patients with TBI.

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METHODS: We identified patients with severe TBI (Glasgow Coma Scale score £8 on admission) between 2004 and 2015 using data from the Japan Trauma Data Bank. Our endpoint was in-hospital mortality. Mixed effects logistic regression models were used to investigate the association between SBP on admission and in-hospital mortality, with hospitals considered as a random effects variable. We also conducted analyses stratified by age (£60 years and >60 years) to determine age-specific optimal levels of SBP.

hypotensive at SBP <100 mm Hg, whereas in older patients, SBP <120 mm Hg should be diagnosed as hypotension.

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RESULTS: A total of 12,537 patients (5665 patients £60 years old and 6872 patients >60 years old) were eligible for the analyses. Overall, SBP of 110 mm Hg was the optimal threshold for hypotension, and adjusted odds ratio and C-statistic for mortality at SBP <110 mm Hg on admission were 1.58 (95% confidence interval, 1.42e1.76, P < 0.001) and 0.78 (95% confidence interval, 0.77e0.79), respectively. Stratified analyses showed that optimal thresholds for hypotension in patients £60 years old and >60 years old were 100 mm Hg and 120 mm Hg.

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CONCLUSIONS: The threshold for hypotension in patients with severe TBI should be redefined and modified by age, and patients £60 years old should be considered

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Key words Hypotension - Mortality - Risk factor - Threshold - Traumatic brain injury -

Abbreviations and Acronyms AIS: Abbreviated Injury Scale CI: Confidence interval GCS: Glasgow Coma Scale JTDB: Japan Trauma Data Bank SBP: Systolic blood pressure TBI: Traumatic brain injury

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INTRODUCTION

T

raumatic brain injury (TBI) is the leading cause of death following trauma. Accurate prognosis of TBI can aid in allocating health care resources, classifying patients, assessing the effectiveness of novel therapies, and counseling patients. It has been recognized that secondary insults to an injured brain can powerfully influence outcomes; hypotension is one of the best studied and significant of these insults. In addition to being an important predictive indicator, hypotension is a criterion to optimize recovery in the future, as its occurrence and severity are amenable to therapeutic interventions. The traditional definition of hypotension—systolic blood pressure (SBP) <90 mm Hg—was determined by the blood pressure distribution among healthy adults1; thus, it is more of a statistical finding than a physiologic one, and few data supporting dogmatic adherence to this arbitrary value exist. There is growing debate on the optimal definition of hypotension in patients with trauma, and studies have proposed a higher SBP as the threshold for hypotension.2-5 However, few studies have attempted to redefine hypotension in patients with TBI, and the optimal threshold for hypotension in TBI remains unclear. In this study, we investigated the level of SBP that correlates to higher mortality in patients with TBI to determine the optimal threshold for hypotension.

From the 1Tertiary Emergency Medical Center, Tokyo Metropolitan Bokutoh Hospital; and 2 Department of Public Health, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan To whom correspondence should be addressed: Keita Shibahashi, M.D. [E-mail: [email protected]] Citation: World Neurosurg. (2018). https://doi.org/10.1016/j.wneu.2018.08.142 Journal homepage: www.WORLDNEUROSURGERY.org Available online: www.sciencedirect.com 1878-8750/$ - see front matter ª 2018 Elsevier Inc. All rights reserved.

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ORIGINAL ARTICLE KEITA SHIBAHASHI ET AL.

HYPOTENSION IN PATIENTS WITH SEVERE TBI

Figure 1. Flow chart showing enrollment of patients with severe traumatic brain injury.

MATERIALS AND METHODS We performed a retrospective cohort study using data derived from the Japan Trauma Data Bank (JTDB). Details regarding the JTDB have been presented elsewhere.6 Briefly, the JTDB was established in 2003 under the main auspices of the Japanese Association for the Surgery of Trauma (Trauma Registry Committee) and the Japanese Association for Acute Medicine (Committee for Clinical Care Evaluations). The aim of the JTDB is to collect nationwide data on patients with trauma, including patient characteristics, vital signs on arrival, examinations and treatments performed, diagnostic codes using the Abbreviated Injury Scale (AIS) and Injury Severity Score,7 probability of survival (calculated using the Trauma and Injury Severity Score),8 and information on discharge from the hospital. Between 2004 and 2015, 260 emergency hospitals, accounting for >95% of tertiary emergency medical centers in Japan, participated in the JTDB. This study was approved by the Institutional Review Board of the Tokyo Metropolitan Bokutoh Hospital. The need for informed consent was waived because the data were collected from existing patients’ records, and the de-identification standard was followed to protect the confidentiality of personal information. Study Populations The study included adult (18 years old) patients with severe TBI after blunt injury. Exclusion criteria were 1) SBP <60 mm Hg on arrival and 2) unknown final outcome (in-hospital mortality). The lower limit of 60 mm Hg was chosen because any reported thresholds in the previous literature were higher than this value.3 Definition The main endpoint was in-hospital mortality. Severe TBI was defined as a Glasgow Coma Scale score 8 on admission, with

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AIS codes indicating head trauma. Major extracranial injuries were defined as a maximum AIS score 3 in body regions other than the head. The year of hospital admittance was dichotomized as early (2004e2009) or late (2010e2015). Statistical Analysis For descriptive statistics, numeric variables are presented as medians with interquartile ranges and were compared using the Mann-Whitney U test. Categorical variables are presented as counts and percentages and were tested for significance using c2 test or Fisher exact test. Mixed effects logistic regression models were used with SBP on admission (increments of 10 mm Hg from 60 mm Hg to >200 mm Hg) as the explanatory variable and hospital identification as a random effect variable. To minimize the risk of falsely identifying significant results, a set of explanatory variables for the regression models was chosen a priori based on biologic plausibility and scientific knowledge.9-11 The selected covariates were age, sex, year of hospital admittance, Glasgow Coma Scale score on arrival, Injury Severity Score, major extracranial injuries, and maximum head AIS score. Variance inflation factors were used to check for multicollinearity. The optimal definitions of hypotension were suggested by the results of the regression analysis, and the best discriminatory power (C-statistic) of the model and adjusted odds ratios and 95% confidence intervals (CIs) to determine the increased odds for mortality with the defined thresholds were calculated. In the stratified analysis, we divided patients into 2 groups by age (60 years and >60 years) because blood pressure is known to increase with age, and the overall prevalence of hypertension increases to approximately 70% in patients 55e64 years of age; after this age, the prevalence of hypertension reaches a plateau.12,13 All statistical tests were 2-tailed, and a P value <0.05 was considered significant. All statistical analyses were performed using EZR (Saitama Medical

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ORIGINAL ARTICLE KEITA SHIBAHASHI ET AL.

HYPOTENSION IN PATIENTS WITH SEVERE TBI

Table 1. Baseline Characteristics of Patients

Number of patients Age, years Male

£60 Years Old

>60 Years Old

5665

6872

40 (26e51)

74 (68e81)

<0.001

4381 (77)

4417 (64)

<0.001

P Value

<0.001

Year of hospital admittance Early (2004e2009)

1883 (33)

1744 (25)

Late (2010e2015)

3782 (67)

5128 (75)

4841 (86)

6350 (92)

Suicide attempt

452 (8)

105 (2)

Assault

118 (2)

55 (1)

Other

24 (0)

30 (0)

Unknown

230 (4)

332 (5)

Cause of trauma Accident

<0.001

Type of trauma Traffic accident, pedestrian

722 (13)

1356 (20)

Fall

353 (6)

1581 (23)

Fall on stairs

599 (11)

1150 (17)

Traffic accident, motorbike

1184 (21)

370 (6)

Free fall

813 (14)

574 (8)

Traffic accident, bicycle

581 (10)

915 (13)

Traffic accident, driver/passenger

762 (14)

321 (5)

Other

458 (8)

301 (4)

Unknown

193 (3)

304 (4)

6 (3e7)

5 (3e7)

<0.001

130 (110e152)

149 (118e178)

<0.001

Head

4 (3e5)

5 (4e5)

<0.001

Face

2 (1e2)

2 (1e2)

0.0040

GCS score on arrival SBP on arrival, mm Hg Maximum AIS score

Face, maximum AIS score >2

165 (3)

76 (1)

Neck

1 (1e3)

2 (1e3)

0.011

Thorax

4 (3e4)

3 (3e4)

0.031

Abdomen

2 (2e3)

3 (2e3)

0.21

Spine

2 (2e3)

2 (2e3)

0.014

Spine, maximum AIS score >2

355 (6)

373 (5)

Upper extremity

2 (2e2)

2 (1e2)

<0.001

Lower extremity

1 (1e1)

1 (1e1)

0.42

Major extracranial injury Injury Severity Score Probability of survival by TRISS model In-hospital mortality

2796 (49)

2417 (35)

<0.001

26 (18e36)

25 (18e33)

<0.001

0.74 (0.45e0.90)

0.45 (0.25e0.63)

<0.001

1785 (32)

4103 (47)

<0.001

Data are presented as number (percentage) or median (interquartile range Q1eQ3). GCS, Glasgow Coma Scale; SBP, systolic blood pressure; AIS, Abbreviated Injury Scale; TRISS, Trauma and Injury Severity Score.

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Table 2. Results of Multiple Logistic Regression Analysis with Mortality as Outcome Variable £60 Years Old

Overall

>60 Years Old

Odds Ratio (95% CI)

P Value

Odds Ratio (95% CI)

P Value

Odds Ratio (95% CI)

P Value

Age, years

1.03 (1.02e1.03)

<0.001*

1.02 (1.01e1.02)

<0.001*

1.04 (1.03e1.04)

<0.001*

Sex, male

0.89 (0.81e0.98)

0.013*

0.77 (0.66e0.89)

<0.001*

0.99 (0.88e1.10)

0.82

Year of hospital admittance Early (2004e2009)

Reference

Reference

Reference

Late (2010e2015)

0.79 (0.72e0.88)

<0.001*

0.76 (0.66e0.88)

<0.001*

0.79 (0.70e0.90)

<0.001*

GCS score on arrival

0.69 (0.67e0.70)

<0.001*

0.68 (0.65e0.70)

<0.001*

0.69 (0.67e0.71)

<0.001*

Major extracranial injury

0.82 (0.72e0.94)

0.0043*

0.73 (0.60e0.89)

0.0019*

0.90 (0.75e1.08)

0.25

Maximum AIS score in the head

1.60 (1.50e1.71)

<0.001*

1.59 (1.45e1.76)

<0.001*

1.62 (1.49e1.77)

<0.001*

ISS

1.03 (1.02e1.04)

<0.001*

1.03 (1.02e1.04)

<0.001*

1.03 (1.02e1.03)

<0.001*

60e69

2.94 (2.20e3.92)

<0.001*

2.96 (1.98e4.42)

<0.001*

3.40 (2.26e5.13)

<0.001*

70e79

2.71 (2.10e3.49)

<0.001*

3.66 (2.56e5.24)

<0.001*

2.20 (1.55e3.11)

<0.001*

80e89

2.06 (1.61e2.63)

<0.001*

2.24 (1.57e3.19)

<0.001*

2.18 (1.56e3.06)

<0.001*

90e99

1.51 (1.20e1.90)

<0.001*

1.60 (1.15e2.22)

0.0048*

1.68 (1.21e2.32)

0.0018*

100e109

1.40 (1.13e1.73)

0.0023*

1.17 (0.85e1.60)

0.33

1.78 (1.32e2.40)

<0.001*

110e119

1.19 (0.97e1.46)

0.094

1.10 (0.82e1.46)

0.54

1.47 (1.10e1.96)

0.0094*

120e129

1.03 (0.84e1.24)

0.80

Reference

1.23 (0.94e1.61)

0.12

SBP on arrival, mm Hg

130e139

Reference

1.11 (0.85e1.46)

0.44

Reference

140e149

1.06 (0.88e1.28)

0.53

1.25 (0.95e1.65)

0.12

1.06 (0.82e1.37)

0.66

150e159

1.15 (0.95e1.39)

0.14

1.11 (0.83e1.48)

0.50

1.34 (1.04e1.72)

0.022*

160e169

1.15 (0.95e1.40)

0.15

1.48 (1.09e2.02)

0.013*

1.15 (0.90e1.49)

0.27

170e179

1.39 (1.12e1.72)

0.0024*

1.62 (1.15e2.27)

0.0055*

1.45 (1.11e1.90)

0.0071*

180e189

1.35 (1.08e1.69)

0.0093*

1.56 (1.05e2.32)

0.029*

1.39 (1.06e1.84)

0.019*

190e199

1.58 (1.24e2.00)

<0.001*

1.67 (1.05e2.67)

0.032*

1.65 (1.24e2.19)

<0.001*

200

1.72 (1.41e2.09)

<0.001*

2.23 (1.56e3.19)

<0.001*

1.79 (1.40e2.27)

<0.001*

CI, confidence interval; GCS, Glasgow Coma Scale; AIS, Abbreviated Injury Scale; ISS, Injury Severity Score; SBP, systolic blood pressure. *Statistically significant.

Center, Jichi Medical University, Saitama, Japan), a graphical user interface for R (R Foundation for Statistical Computing, Vienna, Austria).14 RESULTS Between 2004 and 2015, 236,698 patients were registered in the JTDB, of whom 18,860 met the initial study criteria. There were 6323 patients excluded, leaving 12,537 ultimately eligible for analysis (Figure 1). Patients were divided into 2 groups according to age (5665 patients 60 years old and 6872 patients >60 years old). Patients characteristics are shown in Table 1. Patients >60 years of age had a higher SBP on arrival (130 mm Hg [interquartile range: 110e152 mm Hg] vs. 149 mm Hg

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[interquartile range: 118e178 mm Hg], P < 0.001); they were also more severely injured, and mortality was significantly higher than in patients 60 years of age (32% vs. 47%, P < 0.001). The results of the multiple logistic regression analysis with mortality as the outcome variable are shown in Table 2. Variance inflation factors for multicollinearity were <2.9 among the predetermined explanatory variables in each group, indicating a lack of collinearity in the model. Adjusted odds ratio for mortality versus SBP was plotted and demonstrated a U-shaped relationship (Figures 2e4). In the overall analyses, SBP of 130e139 mm Hg was associated with the lowest odds for mortality. SBP of 60e109 mm Hg on admission was significantly associated with mortality, even after adjusting for possible confounders. These findings suggest an

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ORIGINAL ARTICLE KEITA SHIBAHASHI ET AL.

HYPOTENSION IN PATIENTS WITH SEVERE TBI

Figure 2. Plot of adjusted odds ratios for mortality versus systolic blood pressure on arrival: overall analysis of severe traumatic brain injury.

optimal threshold of 110 mm Hg for hypotension. The adjusted odds ratio and C-statistic for mortality with hypotension defined as SBP <110 mm Hg on admission were 1.58 (95% CI, 1.42e1.76; P < 0.001) and 0.78 (95% CI, 0.77e0.79), respectively. In patients 60 years of age, having SBP of 120e129 mm Hg on admission was associated with the lowest odds for mortality, whereas having SBP of 60e99 mm Hg on admission was significantly associated with increased mortality even after adjusting for possible confounders, suggesting that SBP of 100 mm Hg is the optimal threshold for hypotension in this age group. The adjusted odds ratio and C-statistic for mortality in this group with hypotension defined as SBP <100 mm Hg, on admission were 1.95 (95% CI, 1.64e2.31; P < 0.001) and 0.78 (95% CI, 0.77e0.80), respectively. In patients >60 years of age, having SBP of 130e139 mm Hg on admission was associated with the lowest odds for mortality, whereas having SBP of 60e119 mm Hg on admission was significantly associated with mortality even after adjusting for possible confounders. These results suggest that SBP of 120 mm Hg is the optimal threshold for hypotension in this age group. In patients >60 years of age, the adjusted odds ratio and C-statistic for mortality with hypotension defined as SBP <120 mm Hg on

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admission were 1.45 (95% CI, 1.26e1.65; P < 0.001) and 0.74 (95% CI, 0.73e0.76), respectively. DISCUSSION We conducted this study to determine the optimal threshold of hypotension in patients with severe TBI using a large nationwide database. We found that the optimal SBP after severe TBI depends on age. SBP <100 mm Hg in patients 60 years of age and SBP <120 mm Hg in patients >60 years of age were significantly associated with increased mortality, suggesting that the definition of hypotension after severe TBI should be reconsidered with these values. Secondary injury insults, such as systemic hypotension leading to cerebral hypoperfusion, play a critical role in the development of ischemia after TBI. Hypotension has been repeatedly found to be among the most powerful predictors of outcomes and is one of the few factors amenable to therapeutic modification.9-11 Traditionally, hypotension is defined as SBP <90 mm Hg, and this was the target recommended in the initial iterations of the guidelines of the management of severe TBI.15 More recently, an increasing body of evidence suggests that the odds for mortality increased

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HYPOTENSION IN PATIENTS WITH SEVERE TBI

Figure 3. Plot of adjusted odds ratios for mortality versus systolic blood pressure on arrival: analysis in patients 60 years old.

in patients with TBI with a higher SBP.1-3,16 However, few studies have explored this, and they have caveats in the form of the wide ranges of disease severity and/or the sample size; hence, further studies need to be conducted to redefine the optimal blood pressure threshold for patients with TBI. In the current study, we included only patients with severe TBI with documented anatomic head injuries, and we used a large dataset that allowed us to adjust for confounding factors. To the best of our knowledge, our study is the largest cohort of its kind to date that has focused on patients with severe TBI. Under normal conditions, the brain autoregulates cerebral blood flow over a wide range of blood pressures. This autoregulation allows the cerebral blood flow to remain relatively unchanged over a range of cerebral perfusion pressures, and it is accomplished by changes in the resistance vessel diameters, specifically, vasodilation and consequently cerebral blood volume, under conditions of decreased blood pressure.17 The autoregulatory range is considered to be approximately 50e150 mm Hg in normal adults. In cases of chronic hypertension, structural changes, including arterial intimal and medial thickening, sclerotic plaques, and luminal narrowing, serve to increase cerebrovascular resistance, thereby maintaining a

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normal cerebral blood flow under high-pressure conditions. Thus, both the lower and the upper limits of the autoregulatory range shift toward higher pressure. These adaptive changes result in a consequent impairment of the tolerance to acute hypotension. Therefore, in such cases, the normal blood pressure levels are below the patient’s lower limit of autoregulation, and ischemic damage may result. Considering that the baseline blood pressure of older patients is higher,5,12,13 the results of the current study, which suggest that the definition of hypotension should vary by age and that a higher SBP should be considered hypotension in older patients, are plausible in terms of the right shift of the autoregulatory curve. In addition, decreased physiologic reserve and the ability to compensate for hemodynamic stress may explain the increased mortality at higher SBPs in this population compared with younger patients. In their latest guidelines for the management of severe TBI, the recommendations of the Brain Trauma Foundation state that based on new evidence “maintaining SBP at 100 mm Hg for patients aged 50e69 years or at 110 mm Hg for patients aged 15e49 or >70 years may be considered to decrease mortality and improve outcomes.”3 However, the thresholds do not increase with age, despite the presence of theoretical backgrounds that

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ORIGINAL ARTICLE KEITA SHIBAHASHI ET AL.

HYPOTENSION IN PATIENTS WITH SEVERE TBI

Figure 4. Plot of adjusted odds ratios for mortality versus systolic blood pressure on arrival: analysis in patients >60 years old.

explain why such a rise should be considered. Moreover, the recommendations were based on a study in which the proportion of severe TBI was 27%, thus not providing an adequate number to draw a conclusion for the optimal hypotension threshold in these cases. We believe our study adds to the current literature and that its findings should be considered in the management of patients with severe TBI. Consistent with recent studies that suggest the traditional threshold of hypotension should be re-examined,1-3 the results of the current study indicate a need to redefine a higher threshold for SBP than the traditional value of 90 mm Hg. Our results revealed that the optimal SBP range shifted to the right in older patients, which is physiologically plausible because, as described earlier, the autoregulatory curve of cerebral blood flow also shifts to the right in older patients. We primarily assumed that an optimal threshold exists below which the outcome significantly worsens. However, the plot of adjusted odds for mortality versus SBP demonstrated a U-shaped relationship without any obvious inflection point, implying a continuous relationship between SBP and mortality and not a dichotomous one. Assuming a linear relationship exists between lower SBP and mortality, any recommended threshold would be an

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arbitrary value, dependent on the study design and the sample size.18,19 These results suggest that no physiologically meaningful threshold exists in the acute care of patients with TBI, at least not in the typical sense of the concept. Future guidelines should acknowledge these findings. Nonetheless, it is hard to manage patients with TBI without defining a reference blood pressure for treatment purposes in a clinical setting, even if the relationship between lower SBP and mortality is continuous. We believe our results provide an optimal range for SBP, with cutoff values that better contribute to clinical practice. Further studies focusing on critical physiologic threshold values as well as the efficacy of various therapeutic interventions in decreasing the prevalence of secondary brain insults and improving outcomes are warranted. The potential limitations of this study are as follows. First, this study was a retrospective cohort study and therefore was prone to the biases inherent to this study design. To address these biases, we used a mathematical model to adjust for confounding factors; however, the JTDB did not provide detailed data on several factors (e.g., pupillary reactions to light, coagulopathy, hemoglobin level), which may have biased our results. Second, we assessed 1 measurement in time, which may not reflect the blood pressures

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HYPOTENSION IN PATIENTS WITH SEVERE TBI

during resuscitation; thus, we could not draw conclusions about the effect of therapeutic intervention on hypotension. Although the impact of hypotension as a secondary brain insult on patient outcomes is well established, only preliminary studies have evaluated resuscitation protocols and their effects on outcomes in treating hypotension in patients with severe TBI. Future studies that assess the efficacy of therapeutic interventions in decreasing the prevalence of secondary brain insults and mortality are warranted. Third, the JTDB did not provide information on the causes of death. We speculated that older patients had a higher threshold of hypotension based on the vulnerability of cerebral perfusion; however, it was not possible to draw conclusions about the mechanisms behind our findings.

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CONCLUSIONS The results of our study suggest that the optimal SBP threshold in cases of severe TBI depends on age. We observed that SBP <100 mm Hg in patients 60 years of age and SBP <120 mm Hg in patients >60 years of age were significantly associated with increased mortality. ACKNOWLEDGMENTS We thank the Japanese Association for the Surgery of Trauma (Trauma Registry Committee) and the Japanese Association for Acute Medicine (Committee for Clinical Care Evaluations) for providing the required dataset.

9. Steyerberg EW, Mushkudiani N, Perel P, Butcher I, Lu J, McHugh GS, et al. Predicting outcome after traumatic brain injury: development and international validation of prognostic scores based on admission characteristics. PLoS Med. 2008;5:e165 [discussion: e165]. 10. van Leeuwen N, Lingsma HF, Perel P, Lecky F, Roozenbeek B, Lu J, et al. Prognostic value of major extracranial injury in traumatic brain injury: an individual patient data meta-analysis in 39,274 patients. Neurosurgery. 2012;70:811-818 [discussion: 818]. 11. MRC CRASH Trial Collaborators, Perel P, Arango M, Clayton T, Edwards P, Komolafe E, Poccock S, et al. Predicting outcome after traumatic brain injury: practical prognostic models based on large cohort of international patients. BMJ. 2008;336:425-429. 12. Qaseem A, Wilt TJ, Rich R, Humphrey LL, Frost J, Forciea MA. Pharmacologic treatment of hypertension in adults aged 60 years or older to higher versus lower blood pressure targets: a clinical practice guideline from the American College of Physicians and the American Academy of Family Physicians. Ann Intern Med. 2017;166:430-437. 13. Whelton PK, Carey RM, Aronow WS, Casey DE Jr, Collins KJ, Dennison Himmelfarb C, et al. 2017 ACC/ AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/ PCNA Guideline for the prevention, detection, evaluation, and management of high blood pressure in adults: a report of the American College of Cardiology/ American Heart Association Task Force on Clinical Practice Guidelines. Hypertension. 2018;71:e13-e115. 14. Kanda Y. Investigation of the freely available easyto-use software “EZR” for medical statistics. Bone Marrow Transplant. 2013;48:452-458.

Surgeons. Guidelines for the management of severe traumatic brain injury. J Neurotrauma. 2007;24(suppl 1):S1-S106. 16. Murray GD, Butcher I, McHugh GS, Lu J, Mushkudiani NA, Maas AI, et al. Multivariable prognostic analysis in traumatic brain injury: results from the IMPACT study. J Neurotrauma. 2007; 24:329-337. 17. Tietjen CS, Hurn PD, Ulatowski JA, Kirsch JR. Treatment modalities for hypertensive patients with intracranial pathology: options and risks. Crit Care Med. 1996;24:311-322. 18. Spaite DW, Hu C, Bobrow BJ, Chikani V, Sherrill D, Barnhart B, et al. Mortality and prehospital blood pressure in patients with major traumatic brain injury: implications for the hypotension threshold. JAMA Surg. 2017;152:360-368. 19. Fuller G, Hasler RM, Mealing N, Lawrence T, Woodford M, Juni P, et al. The association between admission systolic blood pressure and mortality in significant traumatic brain injury: a multi-centre cohort study. Injury. 2014;45:612-617. Conflict of interest statement: The authors declare that the article content was composed in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Received 5 February 2018; accepted 17 August 2018 Citation: World Neurosurg. (2018). https://doi.org/10.1016/j.wneu.2018.08.142 Journal homepage: www.WORLDNEUROSURGERY.org Available online: www.sciencedirect.com 1878-8750/$ - see front matter ª 2018 Elsevier Inc. All rights reserved.

15. Brain Trauma Foundation; American Association of Neurological Surgeons; Congress of Neurological

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