Abstract
There are controversies about the effects of alcohol intake shortly before injury on prognosis of traumatic brain injury (TBI) patients. We investigated the association between alcohol intake and functional/survival outcomes in TBI patients, and whether this effect varied according to age and sex. This was a prospective international multicenter cohort study using the Pan-Asian trauma outcomes study registry in Asian-Pacific countries, conducted on adult patients with TBI who visited participating hospitals. The main exposure variable was alcohol intake before injury, and the main outcomes were poor functional recovery (modified Rankin Scale score, 4–6) and in-hospital mortality. Multivariable logistic regression analyses were conducted to estimate the effects of alcohol intake on study outcomes. Interaction analysis between alcohol intake and age/sex were also performed. Among the study population of 12,451, 3263 (26.2%) patients consumed alcohol before injury. In multivariable logistic regression analysis, alcohol intake was associated with lower odds for poor functional recovery [4.4% vs 6.6%, a odds ratio (95% confidence interval): 0.68 (0.56–0.83)] and in-hospital mortality (1.9% vs 3.1%, 0.64 [0.48–0.86]). The alcohol intake had interaction effects with sex for poor functional recovery: 0.59 (0.45–0.75) for male and 0.94 (0.60–1.49) for female (P for-interaction < .01), whereas there were no interaction between alcohol intake and age. In TBI patients, alcohol intake before injury was associated with lower odds of poor functional recovery and in-hospital mortality, and these effects were maintained in the male group in the interaction analyses.
Keywords: alcohol, outcomes, traumatic brain injury
1. Introduction
Traumatic brain injury (TBI) represents a major public health burden and continues to be the most common cause of traumatic mortality and disability.[1] TBI is a catastrophic event that can destroy quality of life of victims and their families, and most patients who survive after severe TBI suffer from high medical costs because of the remaining impaired cognitive function or functional disability.[2] The global age-standardized incidence rate of TBI is estimated at approximately 369 per 100,000 person-years and TBI-related mortality rates were 20.0 in males and 4.6 in females per 100,000 persons-years. Additionally, TBI represents a large economic burden in terms of healthcare.[3] Neurological injuries associated with TBI not only occur immediately after the injury, but also occur continuously over time.[4] The secondary brain injury which occurs due to ongoing brain ischemia increases the mortality of TBI. As such, prevention of secondary brain injury is one of the main goals of treatment of patients with TBI.[5]
Acute alcohol intake before injury has been seen as a risk factor for increasing likelihood of all types of injury including TBI; up to 50% of patients hospitalized with TBI were found to have consumed alcohol at the time of injury.[6] Although alcohol intake is associated with a higher incidence of injury, the effects of alcohol intake on prognosis of TBI remain controversial.[7] Some animal and human studies have reported neuroprotective effects of alcohol for brain injury,[8,9] and in a rodent model, alcohol intake was associated with accentuated neuro-inflammatory changes resulting from TBI.[10] In addition, 2 meta-analyses have reported that alcohol has the beneficial effect of lowering mortality for TBI patients.[11,12] However, other studies have reported that alcohol has no beneficial associations with clinical outcomes after TBI,[13–15] and conversely worsen long-term neuropsychological impairments for TBI patients with alcohol intake.[16]
We hypothesized that alcohol intake before TBI would affect survival and functional outcomes of the patients and that these effects could be different according to the age and sex of TBI patients. This was based on the results of previous studies presenting that the effects of alcohol intake and metabolic kinetics varies according to age and sex.[17,18] The aims of this study are to examine the association between alcohol intake and poor functional recovery and in-hospital mortality in patients with TBI, and whether this effect differs according to age and sex, using Asian data from the Pan-Asian traumatic outcome study (PATOS).
2. Methods
2.1. Study design and setting
This study was a cohort study using a prospective international multicenter trauma registry of PATOS database in Asian-Pacific area from January 2015 to November 2018.[19]
PATOS, a unique, low cost and self-funded collaborative clinical research network, was first initiated in 2013 to build a multicenter registry of injury patients in the Asia-Pacific region. Eighty-five centers participated in this network on a voluntary basis and are from the following countries: China, India, Japan, Korea, Laos, Malaysia, Philippines, Singapore, Taiwan, Thailand, UAE, and Vietnam. Age-standardized mortality rate per 100,000 population of injury of participating countries varied from 25.8 per 100,000 in Japan to as high as 91.4 per 100,000 in India.[20] Within the various countries in Asia-Pacific, there are many differences in trauma care systems, including emergency medical services (EMS) systems. EMS system operations are diverse: hospital-based in 5 countries; fire-department-based in 4 countries; volunteer-based in 2 countries; and public health-based in 1 country. The highest level of EMS providers is physicians in 5 countries, emergency medical technician (EMT)-intermediates in 4 countries, EMT-paramedics in 1 country, EMT-basics in 1 country, and multiple levels in 1 country.[19] Regarding trauma registry, national trauma registry systems have not yet been established in most low- and middle- income countries, and even if such registries do exist, they are often incomplete and rudimentary.[21]
2.2. Data sources
PATOS database is a multicenter trauma registry in compliance with this Asian-Pacific clinical research network. This study reported on injured patients who were transported to emergency departments (EDs) of the participating hospitals, by typical EMS ambulances in developed communities and by various other vehicles in developing communities. All patients with TBI were reported within a week to the registry. Injuries could be of any severity but should meet the World Health Organization case definition: results from road traffic injuries, drowning, poisoning, falls or burns, and violence (assault, self-inflected violence, or acts of war).[22] Participating hospitals and EMS agencies aggregated patients information using multiple sources of data. Prehospital-EMS data were collected from ambulance run sheets and EMS dispatch records. Information on hospital care and patient outcomes were abstracted from inpatient discharge records in EDs, intensive care units and wards of receiving hospitals. Information on long-term outcomes were captured via follow up telephone surveys at 6 and 12 months after hospital discharge. Definitions and coding instructions of all variables were laid out in a data dictionary which was distributed to all participating sites. Data were then collated via an electronic data capture system (see http://epatos.org). The aggregated data was cleaned and managed by the PATOS data quality management committee to address invalid and/or incomplete entries. All sites responded to the PATOS Data quality management committee within 2 weeks of receiving data verification requests.
2.3. Study population
Patients with TBI over 18 years of age who visited participating hospitals ED between January 2015 and November 2018 were included. This study excluded patients with severe injuries to parts other than the head with an abbreviated injury scale (AIS) score of 3 to 6. Cases with unknown information on alcohol intake shortly before injury and modified ranking scale (mRS) score at hospital discharge were also excluded.
Patients with altered consciousness were defined as patients whose Glasgow coma scale (GCS) score were <15 at the time of ED arrival, and severe TBI patients were defined as head injury patients with an AIS score of 3 to 6.
2.4. Study outcomes and variables
The main outcome measure was functional recovery at hospital discharge measured by the mRS score. Poor functional recovery was defined as a mRS score of 4 (moderately severe disability), 5 (severe disability), and 6 (death). The secondary outcome was in-hospital mortality.
The main exposure of this study was alcohol intake before injury. A patient was classified into the alcohol intake group if there was a strong evidence of alcohol consumption within a short time from injury. Physicians or nurses collected information on alcohol intake immediately after patient arrival at the ED, by physical examination and history-taking from the patient, families, and EMS providers.
Data were collected regarding patients demographic information (country of residence, age (18–64 or 65–120), and sex), injury characteristics (mechanism of injury, place of injury, activity at time of injury, and intentionality), prehospital care (ambulance use and prehospital oxygen supply), ED and hospital care (initial vital signs, injury severity of TBI, accompanied injuries, and disposition after ED treatment), and patients outcomes at time of hospital discharge.[19] In addition, we categorized GCS (alert [15]. verbal [13–14], pain [9–12], and unresponsive [3–8]),[23] AIS (mild [1–2] and severe [3–6]),[24] and NISS (mild [1–8], moderate [9–15], severe [16–24], and very severe [25–75]).[25] In our analysis, we dealt with missing data using a multiple imputation approach for reducing the potential bias that might arise from listwise deletion of cases with missing values.
2.5. Statistical analysis
The characteristics of patients according to alcohol intake before injury were compared using Chi-square test for categorical variables and the Wilcoxon rank-sum test for nonparametric distributed continuous variables.
Multivariable logistic regression analyses were performed to estimate the effect sizes of alcohol intake before injury on poor functional recovery at hospital discharge and in-hospital mortality. Crude and adjusted odds ratios (ORs) with 95% confidence interval (CIs) were calculated. The model adjusted for patient factors (age, sex) and injury characteristics (place of injury, activity at time of injury, and severity of TBI). The potential confounders were selected based on directed acyclic graph models.
For sensitivity analysis, multivariable logistic regression analyses were performed to evaluate the effects of alcohol intake before injury on functional and survival outcomes for patients with altered consciousness at time of ED arrival and severe TBI patients. Finally, the interaction between the alcohol intake before injury and age/sex on study outcomes was also analyzed to investigate whether the effects of alcohol intake before injury were modified according to age and/or sex.
All statistical analyses were performed using SAS version 9.4 (SAS institute Inc., Cary, NC). All p-values were 2-tailed, and P < .05 was considered statistically significant.
2.6. Ethics statements
This study complies with the Declaration of Helsinki. This study was approved by the Institutional Review Board of Seoul National University Hospital (IRB No. SNUH-1509-045-702) and the requirement for informed consent was waived due to the retrospective nature of this study.
3. Results
Among the 71,383 injured patients in the PATOS registry, a total of 12,451 TBI patients were enrolled. Patients under 18 years of age (n = 7929), patients without brain injury (n = 44,587), patients with severe injury of an AIS 3 to 6 in parts other than the head (n = 1408), patients with unknown information on alcohol intake (n = 3545) and mRS score at hospital discharge (n = 1463) were excluded (Fig. 1).
Figure 1.
Patient flow. AIS = abbreviated injury scale, PATOS = Pan-Asian traumatic outcome study.
The characteristics of the study population according to the alcohol intake are shown in Table 1. There were 26.2% (3263/12,451) of the total population in the alcohol intake group and 34.1% (591/1733) of TBI patients with altered consciousness at ED arrival in the alcohol intake group. In our study population, those with alcohol intake were younger and more male, and had a higher proportion of injuries due to mechanisms other than road traffic injury. And, patients with alcohol intake had a significantly lower proportion of poor functional recovery at hospital discharge (4.4% vs 6.6%, P value < .01) and in-hospital mortality (1.9% vs 3.1%, P value < .01) compared to those without alcohol intake.
Table 1.
Characteristics of total study population and TBI patients with altered consciousness at ED.
| Total TBI patients | P value | TBI patients with altered consciousness at ED | P value | |||||
|---|---|---|---|---|---|---|---|---|
| Total | Alcohol intake | No-alcohol | Total | Alcohol intake | No-alcohol | |||
| 12,451 (100.0) | 3263 (100.0) | 9188 (100.0) | 1733 (100.0) | 591 (100.0) | 1142 (100.0) | |||
| Country | <.001 | .021 | ||||||
| Korea | 8519 (68.4) | 2433 (74.6) | 6086 (66.2) | 863 (49.8) | 319 (54.0) | 544 (47.6) | ||
| Vietnam | 2168 (17.4) | 389 (11.9) | 1779 (19.4) | 495 (28.6) | 123 (20.8) | 372 (32.6) | ||
| Malaysia | 1448 (11.6) | 292 (8.9) | 1156 (12.6) | 287 (16.6) | 93 (15.7) | 194 (17.0) | ||
| Japan and other | 316 (2.5) | 149 (4.6) | 167 (1.8) | 88 (5.1) | 56 (9.5) | 32 (2.8) | ||
| Age, yr | <.001 | <.001 | ||||||
| 18–30 | 2302 (18.5) | 724 (22.2) | 1578 (17.2) | 338 (16.2) | 94 (21.9) | 244 (14.8) | ||
| 31–40 | 1732 (13.9) | 597 (18.3) | 1135 (12.4) | 278 (13.3) | 79 (18.4) | 199 (12.0) | ||
| 41–50 | 1730 (13.9) | 565 (17.3) | 1165 (12.7) | 242 (11.6) | 71 (16.6) | 171 (10.3) | ||
| 51–60 | 2085 (16.7) | 642 (19.7) | 1443 (15.7) | 314 (15.1) | 73 (17.0) | 241 (14.6) | ||
| 61–70 | 1818 (14.6) | 450 (13.8) | 1368 (14.9) | 312 (15.0) | 61 (14.2) | 251 (15.2) | ||
| 71–80 | 1632 (13.1) | 229 (7.0) | 1403 (15.3) | 358 (17.2) | 40 (9.3) | 318 (19.2) | ||
| 80- | 1149 (9.2) | 56 (1.7) | 1093 (11.9) | 241 (11.6) | 11 (2.6) | 230 (13.9) | ||
| Sex, male | 7983 (64.1) | 2684 (82.3) | 5299 (57.7) | <.001 | 1320 (76.2) | 507 (85.8) | 813 (71.2) | <.001 |
| Place of injury, home | 3070 (24.7) | 559 (17.1) | 2511 (27.3) | <.001 | 323 (18.6) | 68 (11.5) | 255 (22.3) | <.001 |
| Activity, at work | 1518 (12.2) | 88 (2.7) | 1430 (15.6) | <.001 | 333 (19.2) | 28 (4.7) | 305 (26.7) | <.001 |
| Mechanism | <.001 | <.001 | ||||||
| Road traffic injury | 5100 (41.0) | 830 (25.4) | 4270 (46.5) | 892 (51.5) | 246 (41.6) | 646 (56.6) | ||
| Fall/slip down | 4929 (39.6) | 1387 (42.5) | 3542 (38.6) | 599 (34.6) | 214 (36.2) | 385 (33.7) | ||
| Other | 2422 (19.5) | 1046 (32.1) | 1376 (15.0) | 242 (14.0) | 131 (22.2) | 111 (9.7) | ||
| Intentional injury | 1126 (9.0) | 649 (19.9) | 477 (5.2) | <.001 | 95 (5.5) | 60 (10.2) | 35 (3.1) | <.001 |
| Mode of arrival | <.001 | .014 | ||||||
| Ambulance | 9466 (76.0) | 2768 (84.8) | 6698 (72.9) | 1193 (68.8) | 465 (78.7) | 728 (63.7) | ||
| Prehospital oxygen | .241 | <.00 | ||||||
| Yes | 829 (6.7) | 203 (6.2) | 626 (6.8) | 354 (20.4) | 100 (16.9) | 254 (22.2) | ||
| ER SBP (mm Hg) | <.001 | |||||||
| Median (IQR) | 135 (120–154) | 136 (120–154) | 137 (120–154) | <.001 | 130 (110–150) | 126 (111–144) | 130 (110–154) | .012 |
| Shock (<90) | 271 (2.2) | 89 (2.7) | 182 (2.0) | 149 (8.6) | 43 (7.3) | 106 (9.3) | .011 | |
| Unknown | 190 (1.5) | 33 (1.0) | 157 (1.7) | 102 (5.9) | 19 (3.2) | 83 (7.3) | ||
| ER HR (bpm) | <.001 | |||||||
| Median (IQR) | 84 (75–95) | 85 (75–95) | 86 (75–95) | <.001 | 88 (77–100) | 87 (78–99) | 88 (77–100) | .014 |
| Bradycardia (<60) | 550 (4.4) | 92 (2.8) | 458 (5.0) | 95 (5.5) | 26 (4.4) | 69 (6.0) | <.001 | |
| Unknown | 169 (1.4) | 31 (1.0) | 138 (1.5) | 93 (5.4) | 19 (3.2) | 74 (6.5) | ||
| ER GCS | <.001 | <.001 | ||||||
| 15 | 9733 (78.2) | 2397 (73.5) | 7336 (79.8) | (0.0) | (0.0) | (0.0) | ||
| 13–14 | 709 (5.7) | 254 (7.8) | 455 (5.0) | 709 (40.9) | 254 (43.0) | 455 (39.8) | ||
| 9–12 | 500 (4.0) | 194 (5.9) | 306 (3.3) | 500 (28.9) | 194 (32.8) | 306 (26.8) | ||
| 3–8 | 524 (4.2) | 143 (4.4) | 381 (4.1) | 524 (30.2) | 143 (24.2) | 381 (33.4) | ||
| Unknown | 985 (7.9) | 275 (8.4) | 710 (7.7) | (0.0) | (0.0) | (0.0) | ||
| Severity of TBI (AIS) | <.001 | <.001 | ||||||
| 1 | 9156 (73.5) | 2542 (77.9) | 6614 (72.0) | |||||
| 2 | 1209 (9.7) | 292 (8.9) | 917 (10.0) | |||||
| 3 | 1412 (11.3) | 317 (9.7) | 1095 (11.9) | 1412 (67.8) | 317 (73.9) | 1095 (66.2) | ||
| 4 | 147 (1.2) | 30 (0.9) | 117 (1.3) | 147 (7.1) | 30 (7.0) | 117 (7.1) | ||
| 5 | 266 (2.1) | 57 (1.7) | 209 (2.3) | 266 (12.8) | 57 (13.3) | 209 (12.6) | ||
| 6 | 258 (2.1) | 25 (0.8) | 233 (2.5) | 258 (12.4) | 25 (5.8) | 233 (14.1) | ||
| Severity of trauma (NISS) | <.001 | <.001 | ||||||
| 1–8 | 9023 (72.5) | 2545 (78.0) | 6478 (70.5) | 737 (42.5) | 322 (54.5) | 415 (36.3) | ||
| 9–15 | 1495 (12.0) | 323 (9.9) | 1172 (12.8) | 352 (20.3) | 103 (17.4) | 249 (21.8) | ||
| 16–24 | 370 (3.0) | 89 (2.7) | 281 (3.1) | 185 (10.7) | 55 (9.3) | 130 (11.4) | ||
| 25–75 | 556 (4.5) | 90 (2.8) | 466 (5.1) | 250 (14.4) | 47 (8.0) | 203 (17.8) | ||
| Unknown | 1007 (8.1) | 216 (6.6) | 791 (8.6) | 209 (12.1) | 64 (10.8) | 145 (12.7) | ||
| Accompanied injury | ||||||||
| Neck and face | 4829 (38.8) | 1544 (47.3) | 3285 (35.8) | <.001 | 621 (35.8) | 230 (38.9) | 391 (34.2) | .053 |
| Chest | 1037 (8.3) | 205 (6.3) | 832 (9.1) | <.001 | 194 (11.2) | 50 (8.5) | 144 (12.6) | <.001 |
| Abdomen | 543 (4.4) | 111 (3.4) | 432 (4.7) | <.001 | 119 (6.9) | 26 (4.4) | 93 (8.1) | <.001 |
| Spine | 596 (4.8) | 60 (1.8) | 536 (5.8) | <.001 | 72 (4.2) | 15 (2.5) | 57 (5.0) | .021 |
| Extremity | 3023 (24.3) | 577 (17.7) | 2446 (26.6) | <.001 | 396 (22.9) | 120 (20.3) | 276 (24.2) | .068 |
| Other | 410 (3.3) | 110 (3.4) | 300 (3.3) | .769 | 101 (5.8) | 43 (7.3) | 58 (5.1) | .061 |
| Clinical outcomes | ||||||||
| Poor functional recovery | 746 (6.0) | 143 (4.4) | 603 (6.6) | <.001 | 358 (20.7) | 83 (14.0) | 275 (24.1) | <.001 |
| In-hospital mortality | 349 (2.8) | 62 (1.9) | 287 (3.1) | <.001 | 244 (14.1) | 55 (9.3) | 189 (16.5) | <.001 |
AIS = abbreviated injury scale, BPM = beats per minute, ED = emergency department, GCS = Glasgow coma scale, HR = heart rate, NISS = new injury severity score, SBP = systolic blood pressure, TBI = traumatic brain injury.
In patients with altered consciousness at time of ED arrival, the trends were similar; the proportions of patients who had poor functional recovery at hospital discharge were 14.0% and 24.1% (P value < .01) in the group with alcohol intake and in the group without alcohol intake respectively, and the proportions of in-hospital mortality were 9.3% and 16.5% (P value < .01). The characteristics of the study population according to country and age/sex and TBI patients with alert mental state were provided as supplements (Supplemental Digital Content 1, 2, and 3, http://links.lww.com/MD/J430).
The multivariable logistic regression analysis showed that alcohol intake was significantly associated with lower odds of poor functional recovery and in-hospital mortality in TBI patients (adjusted ORs (95% CIs): 0.68 (0.56–0.83) for poor functional recovery and 0.64 (0.48–0.86) for in-hospital mortality) (Table 2).
Table 2.
Multivariable logistic regression analysis for total study population.
| Total | Outcome | Model 1 | Model 2 | ||
|---|---|---|---|---|---|
| N | N | % | aOR (95% CI) | aOR (95% CI) | |
| Total TBI patients | |||||
| Poor functional recovery (MRS ≥ 4) | |||||
| Total | 12,451 | 746 | 6.0 | ||
| Alcohol intake | |||||
| No-alcohol | 9188 | 603 | 6.6 | 1.00 | 1.00 |
| Alcohol intake | 3263 | 143 | 4.4 | 0.65(0.54–0.79) | 0.68 (0.56–0.83) |
| Age | |||||
| 18–64 | 8867 | 448 | 5.1 | 1.00 | 1.00 |
| 65–120 | 3584 | 298 | 8.3 | 1.68 (1.44–1.97) | 1.72 (1.46–2.02) |
| Sex | |||||
| Male | 7983 | 528 | 6.6 | 1.00 | 1.00 |
| Female | 4468 | 218 | 4.9 | 0.63 (0.53–0.74) | 0.66 (0.59–0.74) |
| In-hospital mortality | |||||
| Total | 12,451 | 349 | 2.8 | ||
| Alcohol intake | |||||
| No-alcohol | 9188 | 287 | 3.1 | 1.00 | 1.00 |
| Alcohol intake | 3263 | 62 | 1.9 | 0.63 (0.43–0.75) | 0.64 (0.48–0.86) |
| Age | |||||
| 18–64 | 8867 | 225 | 2.5 | 1.00 | 1.00 |
| 65–120 | 3584 | 124 | 3.5 | 1.34 (1.07–1.68) | 1.56 (1.23–1.97) |
| Sex | |||||
| Male | 7983 | 252 | 3.2 | 1.00 | 1.00 |
| Female | 4468 | 97 | 2.2 | 0.59 (0.47–0.76) | 0.66 (0.52–0.85) |
Model 1: adjusted for age, sex, alcohol intake.
Model 2: adjusted for variables in Model 1, place of injury, activity.
aOR = adjusted odds ratio, CI = confidence interval, MRS = modified rankin scale, TBI = traumatic brain injury.
3.1. Sensitivity analysis
Among the 1733 patients with altered consciousness at the time of ED arrival, the alcohol intake group had lower odds of poor functional recovery [adjusted OR (95% CI): 0.53 (0.34–0.72)] and in-hospital mortality [adjusted OR (95% CI): 0.59 (0.35–0.71)] (Table 3). However, among the 2083 severe TBI patients there were no associations between alcohol intake and the study outcomes [adjusted OR (95% CIs): 1.17 (0.88–1.31] for poor functional recovery and (1.04 [0.82–1.24] for in-hospital mortality).
Table 3.
Sensitivity analysis for TBI patients with altered consciousness and severe TBI patients.
| Total | Outcome | Model 1 | Model 2 | ||
|---|---|---|---|---|---|
| N | N | % | aOR (95% CI) | aOR (95% CI) | |
| TBI patients with altered consciousness | |||||
| Poor functional recovery (MRS ≥ 4) | |||||
| Total | 1733 | 358 | 20.7 | ||
| Alcohol intake | |||||
| No-alcohol | 1142 | 275 | 24.1 | 1.00 | 1.00 |
| Alcohol intake | 591 | 83 | 14.0 | 0.56 (0.42–0.74) | 0.53 (0.34–0.72) |
| In-hospital mortality | |||||
| Total | 1733 | 244 | 14.1 | ||
| Alcohol intake | |||||
| No-alcohol | 1142 | 189 | 16.5 | 1.00 | 1.00 |
| Alcohol intake | 591 | 55 | 9.3 | 0.54 (0.39–0.75) | 0.59 (0.35–0.71) |
| Severe TBI patients | |||||
| Poor functional recovery (MRS ≥ 4) | |||||
| Total | 2083 | 389 | 18.7 | ||
| Alcohol intake | |||||
| No-alcohol | 1654 | 313 | 18.9 | 1.00 | 1.00 |
| Alcohol intake | 429 | 76 | 17.7 | 0.97 (0.73–1.29) | 1.17 (0.88–1.31) |
| In-hospital mortality | |||||
| Total | 2083 | 196 | 9.4 | ||
| Alcohol intake | |||||
| No-alcohol | 1654 | 160 | 9.7 | 1.00 | 1.00 |
| Alcohol intake | 429 | 36 | 8.4 | 0.85 (0.58–1.26) | 1.04 (0.82–1.24) |
Model 1: adjusted for age, sex, alcohol intake.
Model 2: adjusted for variables in Model 1, place of injury, activity, and severity of TBI.
aOR = adjusted odds ratio, CI = confidence interval, MRS = modified rankin scale, TBI = traumatic brain injury.
3.2. Interaction analysis
In interaction analysis assessing whether the effect measures of alcohol intake on the study outcomes varied according to age and sex, there were no interactions between alcohol intake and age. Regarding interaction between alcohol intake and sex, the adjusted OR for the poor functional recovery differed depending on sex of injured patients: the negative association between alcohol intake and poor functional recovery was maintained in the male group, whereas it was nonsignificant in the female group for total study population [adjusted ORs (95% CIs): 0.53 (0.44–0.79) for male vs 0.94 (0.60–1.51) for female, P for-interaction < .01] (Table 4).
Table 4.
Interaction analysis for total study population, TBI patients with altered consciousness, and severe TBI patients.
| Alcohol intake | Alcohol intake | ||||
|---|---|---|---|---|---|
| aOR (95% CI) | P for interaction | aOR (95% CI) | P for interaction | ||
| Total TBI patients | Total TBI patients | ||||
| Poor functional outcome (MRS ≥ 4) | .14 | Poor functional outcome (MRS ≥ 4) | <.01 | ||
| Age, 18–64 | 0.72 (0.53–0.91) | Sex, Male | 0.53 (0.44–0.79) | ||
| Age, 65–120 | 0.54 (0.32–0.83) | Sex, Female | 0.94 (0.60–1.51) | ||
| Mortality | .72 | Mortality | .04 | ||
| Age, 18–64 | 0.62 (0.41–0.81) | Sex, Male | 0.60 (0.42–0.79) | ||
| Age, 65–120 | 0.61 (0.32–1.24) | Sex, Female | 0.79 (0.43–1.59) | ||
| TBI patients with altered consciousness | TBI patients with altered consciousness | ||||
| Poor functional outcome (MRS ≥ 4) | .37 | Poor functional outcome (MRS ≥ 4) | .54 | ||
| Age, 18–64 | 0.44 (0.31–0.73) | Sex, Male | 0.52 (0.33–0.72) | ||
| Age, 65–120 | 0.42 (0.29–0.73) | Sex, Female | 0.61 (0.31–1.16) | ||
| Mortality | .17 | Mortality | .03 | ||
| Age, 18–64 | 0.51 (0.32–0.71) | Sex, Male | 0.51 (0.37–0.77) | ||
| Age, 65–120 | 0.72 (0.34–1.43) | Sex, Female | 0.65 (0.30–1.42) | ||
| Severe TBI patients | Severe TBI patients | ||||
| Poor functional outcome (MRS ≥ 4) | .19 | Poor functional outcome (MRS ≥ 4) | <.01 | ||
| Age, 18–64 | 1.23 (0.82–1.63) | Sex, Male | 0.91 (0.73–1.31) | ||
| Age, 65–120 | 0.69 (0.37–1.29) | Sex, Female | 2.17 (1.09–4.24) | ||
| Mortality | .22 | Mortality | .17 | ||
| Age, 18–64 | 0.82 (0.52–1.35) | Sex, Male | 0.89 (0.54–1.41) | ||
| Age, 65–120 | 1.42 (0.69–2.90) | Sex, Female | 1.39 (0.52–3.24) | ||
aOR = adjusted odds ratio, CI = confidence interval, MRS = Modified Rankin scale, TBI = traumatic brain injury.
4. Discussion
Using a prospective international multicenter registry of injury in the Asia-Pacific region, the study discovered that alcohol intake before brain injury was associated with lower odds of poor functional recovery and in-hospital mortality in adult TBI patients. These trends were maintained in the sensitivity analysis of TBI patients with altered consciousness at time of ED arrival. In an interaction analysis, the association between alcohol intake and better functional recovery was maintained in the male TBI patients. This research contributes to the better understanding of the relationship between alcohol intake before injury and functional/survival outcomes after TBI and will help in developing strategies to improve clinical outcomes in TBI patients.
It is known that up to 50% of patients with TBI drink alcohol shortly before injury; therefore, it is important to try to find out the relationship between alcohol intake and prognosis after TBI.[26] Alcohol intake before injury inhibits an adrenergic response after TBI,[27,28] and increased blood alcohol levels correlate with slowing of the catecholamine response to injury, which lead to improved neurological outcomes after injury.[29] Among TBI patients with positive blood alcohol concentration, the moderate to high concentration group showed lower in-hospital mortality than the lower concentration of alcohol group.[7] Animal studies have postulated a neuroprotective effect of alcohol, including less reduction of cerebral blood flow, more normal glucose metabolism, higher corticosterone values, and less impairment of motor and cognitive functions, which can be neuroprotective.[15,30] However, in experimental study of TBI and hemorrhagic shock porcine model, ethanol administration decreased survival time, impaired the hemodynamic response, and worsened measures of cerebral tissue perfusion.[31] Also, some observational studies reported that the protective effect of the helmet was lost in alcohol intake TBI patients and increased mortality in alcohol intake poly-trauma patients[32,33]
Alcohol intake is accompanied by various complex physiological changes including respiratory impairment, decreased organ blood flow, and increased lactic acid and brain edema.[34] Lower GCS scores were observed in TBI patients with higher blood alcohol concentration, and diagnostic and therapeutic intervention may be delayed in TBI patients with alcohol intake.[35] In addition, alcohol intake may causes irritability when presenting in the ED, which can lead to increased intracranial pressure with higher mortality, and serious complications during hospitalization, including pneumonia.[36,37]
Based on the evidence, the action of alcohol intake regarding the functional/survival outcomes after TBI depends on a various mechanism, and therefore there are controversies about the association between alcohol intake before injury and prognosis of TBI.[38,39] In this study, patients with alcohol intake were more likely to have better functional outcome at hospital discharge and survive to discharge than those without alcohol intake for total study population and TBI patients with altered consciousness at time of ED arrival.
In the severe TBI patients in this study, however, the associations between alcohol intake and functional/survival outcomes were not consistent, whereas, alcohol intake is associated with lower odds of poor functional recovery and in-hospital mortality in patients with mild TBI. Diagnosis and treatment were often delayed in patients with severe TBI with alcohol consumption, which could lead to poor clinical outcomes and undermine the aforementioned beneficial effects of alcohol intake.[35,40] In interaction analysis, there were no interactions between alcohol intake and age, but an interaction effect with sex was observed in that the effect of alcohol intakes on better functional recovery was maintained only in the male TBI patient group. It has been reported in previous rat studies that the neuroprotective effect of alcohol is a sex-dependent trend, but this has not been definitely established.[41,42]
Understanding the characteristics and clinical outcomes of TBI patients with alcohol intake before injury would be helpful in developing strategies to improve functional/survival outcomes in this group. More active evaluation including measuring blood alcohol concentration for alcohol intake in TBI patients are necessary, and further studies on the clinical outcome of TBI according to blood alcohol concentration will be needed in the future.
4.1. Limitation
This study has several limitations that need to be addressed. First, the main exposure of our study as the history of alcohol intake before injury, which was not measured by blood alcohol concentration, but was confirmed by history-taking from patients, families, and EMS providers, there was a possibility that ‘information bias may occur.
Second, information on the type and amount of alcohol intake or data on the chronic alcohol intake history of the patients that could have affected the clinical outcomes of TBI patients, were unavailable. Third, the investigators of the PATOS registry were not blinded to the study hypothesis, which could have led to biased data collection from the data gatherers. Finally, as the study design was not a randomized controlled trial, there could have been some potential biases that were not controlled.
5. Conclusion
Alcohol intake before brain injury was inversely associated with the poorer functional outcome and in-hospital mortality in TBI patients and patients with altered consciousness at time of ED arrival, whereas it was not in the case of severe TBI patients. These effects were maintained only in the male TBI patient group, not in the female TBI patients.
Author contributions
Conceptualization: Sang Do Shin.
Data curation: Eujene Jung.
Formal analysis: Sang Do Shin.
Funding acquisition: Eujene Jung, Young Sun Ro.
Investigation: Young Sun Ro, Joo Jeong, Hyun Ho Ryu.
Methodology: Joo Jeong, Hyun Ho Ryu.
Project administration: Hyun Ho Ryu.
Software: Young Sun Ro, Joo Jeong.
Supervision: Young Sun Ro.
Validation: Young Sun Ro.
Writing – original draft: Eujene Jung.
Writing – review & editing: Eujene Jung, Young Sun Ro.
Supplementary Material
Abbreviations:
- AIS
- abbreviated injury scale
- CI
- confidence interval
- ED
- emergency department
- EMS
- emergency medical service
- EMT
- emergency medical technician
- GCS
- Glasgow coma scale
- mRS
- modified ranking scale
- OR
- odds ratio
- PATOS
- Pan-Asian traumatic outcome study
- TBI
- traumatic brain injury
Supplemental Digital Content is available for this article.
The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.
This study complies with the Declaration of Helsinki. This study was approved by the Institutional Review Board (IRB) of Seoul National University Hospital (IRB No. SNUH-1509-045-702) and the requirement for informed consent was waived due to the retrospective nature of this study.
The authors have no funding and conflicts of interest to disclose.
How to cite this article: Jung E, Ro YS, Jeong J, Ryu HH, Shin SD. Alcohol intake before injury and functional and survival outcomes after traumatic brain injury: Pan-Asian trauma outcomes study (PATOS). Medicine 2023;102:34(e34560).
Contributor Information
Eujene Jung, Email: em.jung.eujene@gmail.com.
Joo Jeong, Email: yukijeje@gmail.com.
Hyun Ho Ryu, Email: em.ryu.hyunho@gmail.com.
Sang Do Shin, Email: sdshin@snu.ac.kr.
References
- [1].Gabriel EJ, Ghajar J, Jagoda A, et al. Guidelines for prehospital management of traumatic brain injury. J Neurotrauma. 2002;19:111–74. [DOI] [PubMed] [Google Scholar]
- [2].Philip AF, Fangman W, Liao J, et al. Helmets prevent motorcycle injuries with significant economic benefits. Traffic Inj Prev. 2013;14:496–500. [DOI] [PubMed] [Google Scholar]
- [3].Abio A, Bovet P, Valentin B, et al. Changes in mortality related to traumatic brain injuries in the seychelles from 1989–2018. Front Neurol. 2021;12:720434. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [4].Godoy DA, Rubiano A, Rabinstein AA, et al. Moderate traumatic brain injury: the grey zone of neurotrauma. Neurocrit Care. 2016;25:306–19. [DOI] [PubMed] [Google Scholar]
- [5].Carney N, Totten AM, O’Reilly C, et al. Guidelines for the management of severe traumatic brain injury, fourth edition. Neurosurgery. 2017;80:6–15. [DOI] [PubMed] [Google Scholar]
- [6].Freedland ES, McMicken DB, D’Onofrio G. Alcohol and trauma. Emerg Med Clin North Am. 1993;11:225–39. [PubMed] [Google Scholar]
- [7].Ding Q, Wang Z, Shen M, et al. Acute alcohol exposure and risk of mortality of patients with traumatic brain injury: a systematic review and meta-analysis. Alcohol Clin Exp Res. 2017;41:1532–40. [DOI] [PubMed] [Google Scholar]
- [8].Teng SX, Katz PS, Maxi JK, et al. Alcohol exposure after mild focal traumatic brain injury impairs neurological recovery and exacerbates localized neuroinflammation. Brain Behav Immun. 2015;45:145–56. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [9].Goodman MD, Makley AT, Campion EM, et al. Preinjury alcohol exposure attenuates the neuroinflammatory response to traumatic brain injury. J Surg Res. 2013;184:1053–8. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [10].Teng SX, Molina PE. Acute alcohol intoxication prolongs neuroinflammation without exacerbating neurobehavioral dysfunction following mild traumatic brain injury. J Neurotrauma. 2014;31:378–86. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [11].Brennan JH, Bernard S, Cameron PA, et al. Ethanol and isolated traumatic brain injury. J Clin Neurosci. 2015;22:1375–81. [DOI] [PubMed] [Google Scholar]
- [12].Raj R, Mikkonen ED, Siironen J, et al. Alcohol and mortality after moderate to severe traumatic brain injury: a meta-analysis of observational studies. J Neurosurg. 2016;124:1684–92. [DOI] [PubMed] [Google Scholar]
- [13].Zink BJ, Stern SA, Wang X, et al. Effects of ethanol in an experimental model of combined traumatic brain injury and hemorrhagic shock. Acad Emerg Med. 1998;5:9–17. [DOI] [PubMed] [Google Scholar]
- [14].Fabian MJ, Proctor KG. Hemodynamic actions of acute ethanol after resuscitation from traumatic brain injury. J Trauma. 2002;53:864–75. [DOI] [PubMed] [Google Scholar]
- [15].Türeci E, Dashti R, Tanriverdi T, et al. Acute ethanol intoxication in a model of traumatic brain injury: the protective role of moderate doses demonstrated by immunoreactivity of synaptophysin in hippocampal neurons. Neurol Res. 2004;26:108–12. [DOI] [PubMed] [Google Scholar]
- [16].Bombardier CH, Thurber CA. Blood alcohol level and early cognitive status after traumatic brain injury. Brain Inj. 1998;12:725–34. [DOI] [PubMed] [Google Scholar]
- [17].Tynjälä J, Kangastupa P, Laatikainen T, et al. Effect of age and gender on the relationship between alcohol consumption and serum GGT: time to recalibrate goals for normal ranges. Alcohol Alcohol. 2012;47:558–62. [DOI] [PubMed] [Google Scholar]
- [18].Choi DH, Ro YS, Kim KH, et al. The association between alcohol intake shortly before arrest and survival outcomes of out-of-hospital cardiac arrest. Resuscitation. 2022;173:39–46. [DOI] [PubMed] [Google Scholar]
- [19].Kong SY, Shin SD, Tanaka H, et al. Pan-Asian trauma outcomes study (PATOS): rationale and methodology of an international and multicenter trauma registry. Prehosp Emerg Care. 2018;22:58–83. [DOI] [PubMed] [Google Scholar]
- [20].WHO. Summary Tables of Mortality Estimates by Cause, Age and Sex, by Country, 2000–2016. World Health Organization; 2016. [Google Scholar]
- [21].Nwomeh BC, Lowell W, Kable R, et al. History and development of trauma registry: lessons from developed to developing countries. World J Emerg Surg. 2006;1:32. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [22].Berdowski J, Berg RA, Tijssen JG, et al. Global incidences of out-of-hospital cardiac arrest and survival rates: systematic review of 67 prospective studies. Resuscitation. 2010;81:1479–87. [DOI] [PubMed] [Google Scholar]
- [23].Kelly CA, Upex A, Bateman DN. Comparison of consciousness level assessment in the poisoned patient using the alert/verbal/painful/unresponsive scale and the Glasgow coma scale. Ann Emerg Med. 2004;44:108–13. [DOI] [PubMed] [Google Scholar]
- [24].Zonfrillo MR, Weaver AA, Gillich PJ, et al. New methodology for an expert-designed map from international classification of diseases (ICD) to abbreviated injury scale (AIS) 3+ severity injury. Traffic Inj Prev. 2015;16(sup2):S197–200. [DOI] [PubMed] [Google Scholar]
- [25].Bulger EM, Nathens AB, Rivara FP, et al. Management of severe head injury: institutional variations in care and effect on outcome. Crit Care Med. 2002;30:1870–6. [DOI] [PubMed] [Google Scholar]
- [26].Shandro JR, Rivara FP, Wang J, et al. Alcohol and risk of mortality in patients with traumatic brain injury. J Trauma. 2009;66:1584–90. [DOI] [PubMed] [Google Scholar]
- [27].Woolf P, Cox C, Kelly M, et al. The adrenocortical response to brain injury: correlation with the severity of neurologic dysfunction, effects of intoxication, and patient outcome. Alcohol Clin Exp Res. 1990;14:917–21. [DOI] [PubMed] [Google Scholar]
- [28].Woolf PD, Cox C, McDonald J, et al. Effects of intoxication on the catecholamine response to multisystem injury. J Trauma. 1991;31:1271–5. [DOI] [PubMed] [Google Scholar]
- [29].Inaba K, Teixeira PG, David J-S, et al. Beta-blockers in isolated blunt head injury. J Am Coll Surg. 2008;206:432–8. [DOI] [PubMed] [Google Scholar]
- [30].Kelly DF, Kozlowski DA, Haddad E, et al. Ethanol reduces metabolic uncoupling following experimental head injury. J Neurotrauma. 2000;17:261–72. [DOI] [PubMed] [Google Scholar]
- [31].Zink BJ, Syverud SA, Dronen SC, et al. The effect of ethanol on survival time in hemorrhagic shock in an unanesthetized swine model. Ann Emerg Med. 1988;17:15–9. [DOI] [PubMed] [Google Scholar]
- [32].Pories SE, Gamelli RL, Vacek P, et al. Intoxication and injury. J Trauma. 1992;32:60–4. [DOI] [PubMed] [Google Scholar]
- [33].Luna GK, Maier RV, Sowder L, et al. The influence of ethanol intoxication on outcome of injured motorcyclists. J Trauma. 1984;24:695–700. [DOI] [PubMed] [Google Scholar]
- [34].Opreanu RC, Kuhn D, Basson MD. Influence of alcohol on mortality in traumatic brain injury. J Am Coll Surg. 2010;210:997–1007. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [35].Stuke L, Diaz-Arrastia R, Gentilello LM, et al. Effect of alcohol on Glasgow coma scale in head-injured patients. Ann Surg. 2007;245:651–5. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [36].Gurney JG, Rivara FP, Mueller BA, et al. The effects of alcohol intoxication on the initial treatment and hospital course of patients with acute brain injury. J Trauma. 1992;33:709–13. [DOI] [PubMed] [Google Scholar]
- [37].Shih H-C, Hu S-C, Yang C-C, et al. Alcohol intoxication increases morbidity in drivers involved in motor vehicle accidents. Am J Emerg Med. 2003;21:91–4. [DOI] [PubMed] [Google Scholar]
- [38].Scheenen ME, de Koning ME, van der Horn HJ, et al. Acute alcohol intoxication in patients with mild traumatic brain injury: characteristics, recovery, and outcome. J Neurotrauma. 2016;33:339–45. [DOI] [PubMed] [Google Scholar]
- [39].Asmaro K, Fu P, Ding Y. Neuroprotection & mechanism of ethanol in stroke and traumatic brain injury therapy: new prospects for an ancient drug. Curr Drug Targets. 2013;14:74–80. [DOI] [PubMed] [Google Scholar]
- [40].Shahin H, Gopinath SP, Robertson CS. Influence of alcohol on early Glasgow coma scale in head-injured patients. J Trauma. 2010;69:1176–81. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [41].Caslin B, Maguire C, Karmakar A, et al. Alcohol shifts gut microbial networks and ameliorates a murine model of neuroinflammation in a sex-specific pattern. Proc Natl Acad Sci USA. 2019;116:25808–15. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [42].Ziv Y, Rahamim N, Lezmy N, et al. Activity-dependent neuroprotective protein (ADNP) is an alcohol-responsive gene and negative regulator of alcohol consumption in female mice. Neuropsychopharmacology. 2019;44:415–24. [DOI] [PMC free article] [PubMed] [Google Scholar]
Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.