Keywords cranio cerebral trauma - alcohol intoxication - cocaine - marijuana
Palavras-chave traumatismo cranioencefálico - intoxicação alcoólica - cocaína - maconha
Introduction
Traumatic brain injury (TBI) is one of the biggest causes of mortality in the modern
era. Young men are more involved in most statistics, perhaps because they take more
risks in traffic and are more likely to use alcohol and illicit drugs.[1 ]
[2 ] TBI is considered a major public health problem worldwide, as it incurs high socioeconomic
costs, requiring prolonged hospitalizations and specialized treatments.[3 ] It is estimated that in Brazil the annual costs of hospitalization for patients
suffering from traumatic brain injury are US$ 70,960.0004 or 376,698,256.00 reais
(US dollar exchange rate as on 08/07/2022; source: Web site of the Central Bank of
Brazil – bcb.gov.br). Among the most common causes of TBI are transport accidents,
falls, assaults and being run over. Added to these factors is the use of alcoholic
beverages and drugs such as marijuana and cocaine. In Brazil, there are very few publications
referring to moderate and severe TBI associated with the use of alcohol and illicit
drugs. The present study aims to describe the epidemiological characteristics of patients
with severe and moderate TBI, treated at the emergency room of the Hospital of Clinics,
UFU (Federal University of Uberlândia), from September 2020 through to December 2021
(period of the Covid-19 pandemic) and their associations with the use of alcohol,
cocaine and marijuana.
Methods
Study Delimitation and Population
A descriptive, cross-sectional, qualitative and quantitative study was performed on
individuals treated at the Emergency Room of the Hospital of Clinics (HC) of the Federal
University of Uberlândia (UFU), with a diagnosis of severe and moderate TBI, over
the period from September 1st, 2020, through to December 31st, 2021, aged 18 years
or over. Severe injuries were classified as those with a score of 3 to 8 and moderate
those with a score of 9 to 12 on the Glasgow Coma Scale (GCS) ([Fig. 1 ]).
Fig. 1 Glasgow Coma Scale.
The study was approved by the Ethics and Research Committee of the Federal University
of Uberlândia, under CAAE (Certificate of Ethical Presentation) no. 29782820.0.0000.5152
and notion no. 4.041.608, and in all cases an informed consent statement was collected.
Data Collection and Variables Studied
The sample collection was performed exclusively by the same previously trained residents
of the Neurosurgery Department of the Hospital of Clinics during the whole period,
following the instructions on the test package.
Patients, immediately after initial care, were submitted to the saliva alcohol test
using the Assure Saliva Alcohol Test, produced by Assure Tech (Hangzhou) Co. Ltd.
This is a chromatographic immunoassay test based on an alcohol-sensitive enzyme reaction.
It consists of a plastic strip with a small highly specific pad fixed on the tip containing
Tetramethylbenzidine, Alcohol Oxidase, Peroxidase and other additives. Once this pad
comes into contact with fresh saliva, it changes color depending on the concentration
of alcohol present ([Fig. 3a ]).
For the qualitative measurement of cocaine and marijuana metabolites in urine, the
Assure Multi 2 Test was used, produced by Assure Tech (Hangzhou) Co. Ltd. The test
is an immunoassay based on the principle of competitive binding. This test consists
of placing three drops of urine in a cassette filled with anti-marijuana and anti-cocaine
antibodies. If these drugs are present in the patient's urine, it will produce a red
line in the control region and will not appear at the indicated location for the drugs,
thus indicating a positive test ([Fig. 2a and ]
[2b ]).
Fig. 2 (A) Image of positive and negative tests for marijuana and cocaine: there was the
appearance of a red line on C (control) and no appearance of a line for THC, indicating
a positive test for marijuana. (B) Image of positive and negative tests for marijuana
and cocaine: there was the appearance of a red line on C (control) and for THC, but
not for cocaine, indicating a positive result for this drug. (C) Image of positive
and negative tests for marijuana and cocaine: there was only the appearance of a red
line on C and no appearance of a line on THC and COC, indicating a positive result
for marijuana and cocaine. (D) - Image of positive and negative tests for marijuana
and cocaine: appearance of a red line on C, THC and COC, indicating a negative test.
C – control. COC –cocaine. THC - tetrahydrocannabinol.
Fig. 3 (A) Image of positive and negative tests for alcohol: A- Test showing a greenish
coloration of the strip pad, indicating positivity for alcohol at a concentration
of 0.04%. (B) – Image of positive and negative tests for alcohol: test showing no
change in coloring, therefore negative for alcohol.
Information related to the trauma was collected using a questionnaire made specifically
for this purpose (Annex 2).
Statistical Data Analysis Methods
Qualitative data were described with absolute and relative frequency. Quantitative
data were described with the mean and 95% confidence interval error for the mean (normally
distributed data) or were described with the median and interquartile range (non-normal
distribution). When necessary for the analyses, discrete or continuous quantitative
variables were dichotomized for better description of the data due to representativeness
or adjustment to inferential analyses.
To compare the data of the quantitative variables between the two groups, the data
for each group were tested for normality using the Shapiro-Wilk test. Where both groups
were normal, the differences between the means were tested with Student's t -test for homogeneous and/or heterogeneous variances, and when at least one of the
groups was not normal, the medians were compared using the unpaired Wilcoxon test
(Mann-Whitney).
The independence between the groups and qualitative variables was tested with the
Chi-Square test of independence (when expected frequencies were greater than five)
or with Fisher's Exact test (when at least one of the expected frequencies was less
than five). The Chi-Square test had continuity correction in the 2 × 2 contingency
Tables (2 rows by 2 columns).
For all analyses the data were analyzed in SPSS software version 19.0 or in the R
environment (R CORE TEAM 2019). A significance of 5% was adopted for all analyses.
Results
Of a total of 168(one hundred and sixty-eight) patients treated at the ER of the Hospital
of Clinics with a diagnosis of moderate and severe TBI over the period of the 1st
of September 2020 to the 31st of December 2021, 5(five) patients were excluded for
being underage and 8(eight) patients were excluded for having died shortly after initial
care. Of the remaining 155(one hundred and fifty-five) patients, 80(eighty) were studied,
which represent 51.6% of all patients treated over this period.75(seventy-five) patients
were excluded, being that for 18 (eighteen) of them, the person responsible for the
patient was not present at the time of initial care and for 57(fifty-seven), the accompanying
person did not agree to sign the consent forms. Thirty-three (41.25%) tested negative
for any of the drugs. Forty-seven patients (58.75%) tested positive of those, 28(twenty-eight)
were positive for alcohol, 23(twenty-three) for cocaine and 22(twenty-two) for marijuana.
As for the isolated use of substances, 18(eighteen) patients tested positive only
for alcohol, 4 (four) for cocaine and 5 (five) for marijuana. Twenty patients tested
positive for a combination of the three drugs ([Table 3 ]).
Of these 80(eighty) patients, 72(90%) were male and eight (10%) were female. The average
age was 41.9 years old. Fifty-one patients (63.7%) were from Uberlândia and 29 patients
(36.3%) were from other locations. The accidents occurred predominantly at night (52.5%)
and on midweek days (65%).
The most common types of accident were transport accidents (53.8%) and falls (22.5%),
followed by aggression (16.2%) and being run over (7.5%). Regarding the types of vehicles,
accidents involving motorbikes and cars were of a similar incidence (28.75%) and others
(bicycle/4, truck/1, tractor/1) 7.5%. In 40 cases (50%) the victim was the driver
of the vehicle and in five (6.2%), a passenger. One case was not informed. As for
seat belts, just 1.2% of patients were wearing one, 8.7% were not, and 90.1% was not
informed. Of 23 motorbike accidents and 5 bicycle accidents, 13(thirteen) patients
were wearing a helmet,8(eight) were not, and 7(seven) were not informed. Regarding
the types of brain injury shown on tomography, multiple injuries (more than one type
of injury) were predominant (46.2%), followed by traumatic subarachnoid hemorrhage
(30%), diffuse injuries (12.5%), bruising (7.5%) and contusions (3.8%). Of the 80
patients tested, 82.5% presented severe TBI and 17.5% moderate TBI. Surgical treatment
was performed on 27.5% of the patients. Only 13.85% of the patients were resuscitated
on the site of the accident. The total mortality rate was 16.2% and 83.8% of patients
were released ([Table 1 ]).
Table 1
Descriptive Analysis of Variable Data
Variable
Modality
n (%)
Sex
Female
8(10%)
Male
72(90%)
Location
Other
29(36.3%)
Uberlandia
51(63.7%)
Time of Accident
Daytime
38(47.5%)
Nighttime
42(52.5%)
Day of the Week
Weekend
28(35%)
Midweek
52(65%)
Holiday
Yes
4(5%)
No
76(95%)
Typeof Accident
Aggression
13(16.2%)
Run over
6(7.5%)
Fall
18(22.5%)
Transport
43(53.8%)
Victim
Passenger
5(6.2%)
Driver
40(50%)
Vehicle
Motorbike
23(28.75%)
Car
23(28.75%)
Other*
6(7.5%)
Use of Seatbelt
No
7(30.4%)
Yes
1(4.34%)
Use of Helmet
No
8(34.7%)
Yes
13(56.3%)
Alcohol
No
52(65%)
Yes
28(35%)
Marijuana
No
58(72.5%)
Yes
22(27.5%)
Cocaine
No
57(71.3%)
Yes
23(28.7%)
Brain Injury
Diffuse Injury**
10(12.5%)
Contusions
3(3.8%)
Bruising
6(7.5%)
Traumatic SAH
24(30%)
Multiple Injuries***
37(46.2%)
Severity
Moderate
14(17.5%)
Severe
66(82.5%)
Surgery
No
58(72.5%)
Yes
22(27.5%)
Evolution
Death
13(16.2%)
Release
67(83.8%)
Resuscitation at the Site of the Accident
Yes
11(13.8%)
No
69(86.2%)
Alcohol and Cocaine
Yes
9(11.2%)
No
71(88.8%)
Cocaine and Marijuana
Yes
15(18.7%)
No
65(81.3%)
Alcohol and Marijuana
Yes
7(8.7%)
No
73(91.3%)
Alcohol, Marijuana and Cocaine
Yes
7(8.7%)
No
73(91.3%)
Agression
Yes
13(83.7%)
No
67(16.3%)
No drug use
Yes
33(41.25%)
No
47(58.75%)
Abbreviation: SAH, Subarachnoid Hemorrhage.
Key : n: number of patients. Other*: truck (1), bus (1) and bicycle (4).
Diffuse injury**: cerebral o edema and diffuse axonal injury.
Multiple injury***: associations between focal lesions.
Table 2
Descriptive analysis of the stratified database in patients with alcohol, marijuana
and cocaine consumption (qualitative variables)
Variable
Modality
No
Yes
n (%)
n (%)
Statistics(p )
Type of Accident
Aggression
7(13.5%)
6(21.4%)
X2
=1.131 0.77
Run over
4(7.7%)
2(7.1%)
Fall
13(25%)
5(17.9%)
Transport
28(53.8%)
15(53.6%)
Evolution
Death
13(25%)
0(0%)
0.003
Release
39(75%)
28(100%)
Agression
No
45(86.5%)
22(78.6%)
0.362
Yes
7(13.5%)
6(21.4%)
Abbreviations: n, number of patients; X2
, Chi-square statistic; p: probability.
The cocaine and marijuana tests performed on urine samples and the alcohol on saliva
samples were then analyzed in the emergency room and their images recorded ([Fig. 1 ]). Positive testing for alcohol was found in 28 patients (35%). Marijuana and cocaine
were detected in 22 (27.5%) and 23 (28.7%) of patients, respectively ([Table 1 ]). As for the patients under the influence of alcohol, transport accidents were predominant
in 15 (53.6%) followed by aggression in 6 (21.4%), with a zero hospital mortality
rate and an average number of days of hospitalization of 23.98 ± 5.94 ([Table 3 ]).
Table 3
Descriptive analysis of the stratified database in patients with alcohol, marijuana
and cocaine consumption (quantitative variables)
Drug
Variable
No
Yes
Statistic
Average ± CI95%
Median (IQR)
Average ± CI95%
Median (IQR)
Z(P)
Alcohol
Age (Years)
42.42 ± 4.37
42(18)
40.93 ± 6.04
39(26)
701(0.785)
Duration of Hospitalization
23.98 ± 5.94
20(28)
25.71 ± 11.04
13(31)
699.5(0.774)
Marijuana
Age (Years)
44.88 ± 4.19
43.5 (21)
34.05 ± 5.15
34 (19)
386 (0.007)
Duration of Hospitalization
25.21 ± 6.39
18(28)
22.95 ± 10.41
14(27)
591(0.612)
Cocaine
Age (Years)
44.04 ± 4.21
43 (20)
36.61 ± 5.96
36 (23)
484.5 (0.069)
Duration of Hospitalization
22.77 ± 6.18
14(26)
29.09 ± 11.02
21(34)
546.5(0.246)
Abbreviations: IQR, interquartile range; p, probability; Z , statistic Z approximate for the Mann-Whitney test.
In patients positive for cocaine use, the rate of transport accidents was 43.5%. Assaults
totalled 21.7% and mortality was 17.4%, with an average length of hospitalization
of 22.7 ± 6.18 ([Table 3 ]). Among those positive for marijuana, transport accidents also predominated (50%),
followed by aggression and falls (22.7%), with six deaths and an average number of
days of hospitalization of 25.21 ± 6.39 ([Table 3 ]). When analyzing the variables age and length of hospitalization for the three drugs
tested, no significant differences were observed ([Table 3 ]).
Among the 9 (nine) patients positive for the concomitant use of alcohol and cocaine,
5 (five) were victims of transport accidents, 2 (two) of aggression, 1 (one) of being
run over and 1 (one) of falling, with a mortality rate of zero and a mean of 23.69 ± 5.32
days of hospitalization. Regarding the association between alcohol and marijuana,
of 7 (seven) patients, transport accidents predominated at 5 (five), followed by aggression
at 1 (one) and falling at 1 (one), with no cases of being run over in this association.
Mortality was zero, with an average length of hospitalization of 24.52 ± 6.04 days.
For the 15 (fifteen) patients with positive association between cocaine and marijuana,
6 (six) were victims of a transport accident, 5 (five) of a fall, 3 (three) of aggression
and 1 (one) of being run over. Mortality was 13.3% and the average hospital stay was
25.32 ± 6.04 days. We also observed the concomitant use of the three tested substances,
alcohol, marijuana and cocaine, in 7 (seven) patients, with a predominance of transport
accidents at 5 (five), aggression at 1 (one) and a fall at 1 (one). Nobody was run
over in this association. Mortality was zero and the average length of hospitalization
was 24.52 ± 5.45 days.
Discussion
Samples from 80 patients were analyzed and we found 28 cases (35%) positive for alcohol
in saliva. The average hospitalization was 25.71 ± 11.04 days to 23.98 ± 5.94 days
for those not under the influence of alcohol, with no statistical difference ([Table 3 ]). It is interesting to note that hospital mortality was zero in patients positive
for alcohol, in contrast to a mortality of 25% (13 cases) in those negative for alcohol.
Mortality is related to the severity of the trauma and to other associated injuries,
and not necessarily to the use of alcohol.[5 ]
[6 ] Alcohol causes psychoactive effects such as euphoria, disinhibition, drowsiness
and inattention[7 ]and is associated with more than 50% of injuries that require admission to trauma
centres,[8 ] however its effect is temporary due to its short life. We chose to use a test for
measuring alcohol in saliva and not in blood (alcoholaemia), as it is a non-invasive
method of low technical complexity, it does not require storage of the collected material,
and the result is obtained immediately.
We found positivity for alcohol in 35% of the patients evaluated, data similar to
those of Lindembaum (1989).[1 ] Other studies found positivity in 22.8% and 37% respectively.[9 ]
[10 ] Our values are similar to those found in these same bibliographic citations.[9 ]
[10 ] When comparing our data with those found by Faria (2008)[11 ] who observed a positive blood alcohol level of 39.3%, it can be inferred that under
the conditions of the dry law, there is no significant difference. Our study was performed
under Decree 6,489 of 19/06/2008, which in turn became Law 11,705, popularly known
as the Dry Law, and other laws that prohibited the sale of alcohol due to the Covid-19
pandemic. We expected that the ban on the sale of alcoholic beverages in this period
would lead to a reduction in the percentage of positivity, which did not happen.
Research performed in the city of Seattle, Washington, USA, studying TBI patients
admitted to a neurosurgical intensive care unit, mentions the need to measure blood
alcohol. Signs such as agitation, tachycardia and hypertension can manifest in both
alcohol intoxication and intracranial hypertension, which could confuse the diagnosis
and delay treatment.[12 ]
We found 27.5% of positive cases for marijuana, practically, in absolute terms, triple
the cases found by Faria (2011).[13 ] Hawley (2018)[14 ]in the state of Colorado, USA, identified in his work that 74% of patients with severe
and moderate TBI had used marijuana, of those, 63% having used for recreational purposes,
72% to reduce anxiety and stress, and 55% to control insomnia. We did not collect
data on our patients' activities. Faria (2008)[11 ]observed that this event occurred in male patients, during the night, on weekends,
and mainly within an age group from 50 to 59 years old. Our study showed a higher
incidence of TBI at night on weekdays, which differs from other studies.[3 ]
[15 ] There was a predominance in the age groups from 21 to 25 years old and from 36 to
40 years old for marijuana. The observed mortality was 27.3% and 14.3%[16 ]respectively. Regarding the types of accidents, we observed that in this group that
transport accidents corresponded to 50%, followed by falls and assaults at 22.7% each.
The average length of hospitalization was 25.21 ± 6.39 days.
There are few studies in Brazil relating the use of cocaine to TBI, probably due to
underreporting and a lack of health policies that involve research in emergency units
as a routine of care. We found that 28.7% of the patients in our study tested positive
for cocaine, a higher frequency than that found by Faria,[12 ] which was 13.9%. In both, the use predominated in males and in young people. In
these cases, transport accidents were the most common type. Faria observed a positive
association between cocaine and trauma from aggression, when compared with other causes.[13 ] In our study, the main cause was transport accidents (43.5%), followed by falls
(26.1%) and aggression (21.7%). A survey showed that 29.5% of cocaine-dependent individuals
reported having suffered TBI during their lifetime compared with the 8% control,[17 ] emphasizing the importance of this association.
Faria[16 ] reports in his study that the associations between alcohol and cocaine and between
alcohol and marijuana were the most frequent, followed by the association of the three
drugs. We found positivity in the association between alcohol and cocaine at 11.25%,
alcohol and marijuana at 8.75%, and alcohol, marijuana and cocaine at 8.75%.
A previous study found aggression to be the most common cause of trauma associated
with the use of alcohol, marijuana and cocaine.[1 ] In the current study, we found transport accidents to be the most common cause,
followed by aggression and falls.
Studies performed in the USA showed that 35 to 80% of all patients hospitalized for
trauma tested positive for illicit drugs.[18 ]
[19 ] In Brazil, despite intensive surveillance by the authorities in the fight against
drug trafficking (80,607 tonnes of cocaine and 27,124 tonnes of marijuana were seized
from 2020 to November 2021),[20 ] the presence of marijuana and cocaine associated with severe and moderate TBI may
be underestimated. We emphasize that in our country there is no obligation to investigate
these drugs in the emergency care departments of our hospitals.
Conclusion
An association was observed between the use of alcohol, cocaine and marijuana with
moderate and severe TBI in patients attended at the Emergency Room of the Hospital
of Clinics of the Federal University of Uberlândia. The percentage of patients positive
for cocaine (28.7%) and marijuana (27.5%) increased when compared with a study performed
at this institution in 2003, when positivity was observed for cocaine (13.9%) and
marijuana (8.2%). A future study will be necessary to investigate the causal nexus
of these associations.
Limitations
Difficulty in acquiring tests for the dosage of alcohol in saliva and for the dosage
of cocaine and marijuana in urine during the period of the Covid-19 pandemic.
Several family members or guardians were either not identified or refused to sign
the consent form.
Difficulty in implementing a routine for collecting the tests in the emergency room.
