Risk Factors for Delirium in Trauma Patients:

The Impact ofEthanol Use and Lack of Insurance

BERNARDINO C BRANCO, M.D.,* KENIIINABA, M.D.,* MARKO BUKUR, M.D.,t PEEP TALVING, M.D., PH.D.,*
MATTHEW OLIVER, M.D.,* lEAN-STEPHANE DAVID, M.D.,t LYDIA LAM, M.D.,*
DEMETRIOS DEMETRIADES, M.D., PH.D.*

From the *Division of Trauma and Surgical Critical Care, University of Southern California, Los Angeles,
California; f Division of Trauma and Critical Care, Cedars-Sinai Medical Center, Los Angeles,
California; and the fDepartment of Anesthesiology & Critical Care, Lyon-Sud Hospital,
Hospital Civilis de Lyon and Claude Bernard University, Lyon, France
The purpose of this study was to examine independent risk factors, and in particular the impact of
alcohol on the development of delirium, in a cohort of trauma patients screened for ethanol ingestion on admission to hospital. The National Trauma Databank (v. 7.0) was used to identify all
patients 18 years or older screened for ethanol on admission. Patients who developed delirium
were compared with those who did not. Stepwise logistic regression analysis was used to identify
independent risk factors for the development of delirium. A total of 504,839 patients with
admission ethanol levels were identified. Of those, 2,909 (0.6%) developed delirium. Patients
developing delirium were significantly older, more frequently male, and more likely to sustain
thermal injuries and falls. Patients developing delirium had more comorbidities including
chronic ethanol use (19.1% vs 4.5%, P < 0.001) and cardiovascular disease (21.5% vs 12.2%, P <
0.001). On admission, patients developing delirium were more likely to be intoxicated with ethanol (55.4% vs 26.5%, P < 0.001) and were more likely to be uninsured (17.8% vs 0.9%, P < 0.001). A
stepwise logistic regression model identified lack of insurance, positive ethanol on admission,
chronic ethanol use. Intensive Care Unit admission, age > 55 years, bums. Medicare insurance,
falls, and history of cardiovascular disease as independent risk factors for the development of
delirium. The incidence of delirium in this trauma patient cohort was 0.6 per cent. The above risk
factors were independently associated with the development of delirium. This data may be
helpful in designing interventions to prevent delirium.

HE DEVELOPMENT OF DELIRIUM during hospital admission is associated with significant morbidity,

Previous reports have documented increased complication rates, prolonged Intensive Care Unit (ICU)
length of stay (LOS) and hospital LOS when delirium
develops, resulfing in an increase in hospitalizafion
and treatment costs.'^ Moreover, delirium may be
difficult to disfinguish from sepsis, shock, or progression of traumafic brain injury, complicating the
diagnosis and treatment of these conditions.^
Ethanol use is prevalent in pafients admitted to a
trauma center after injury. It is estimated that a quarter
of pafients admitted to urban hospitals are posifive for
ethanol.^ These patients may be at significant risk of
developing delirium. To date, very few studies have examined the risk factors associated with the development

of delirium in trauma pafients.'^- ^ These studies were

limited by a small sample size and the lack of logisdc
regression analysis to identify predictors for the development of delirium.
The idenfificafion of pafients at risk of developing
delirium is important as it may facilitate the inifiation
of prophylacfic treatment, allow early diagnosis, and
provide effecfive interventions for those who develop
delirium despite prophylaxis with the practical goal of
reducing complicafions such as self-extubafion, falls,
and life-threatening agitation. The purpose of the
present study was to examine the prevalence of delirium in an acutely injured pafient cohort and to
idenfify independent risk factors for its development,
Methods

~,

T^ , u

The Nafional Trauma Databank (NTDB) of the

Address eorrespondence and repnnt requests to Kenji Inaba,

M.D., Division of Trauma and Surgieal Critieal Care, University of

Southern California, 1200 North State Street, Room CL5100, Los
Angeles, CA 90033-4525. E-mail: kinaba@surgery.use.edu.

,,

^_

.-,,>

j ^

yy..'

American College of Surgeons version 7.0 was queried

to idenfify all trauma pafients 18 years or older. This
version of the NTDB contains deidenfified data from

621

THE AMERICAN SURGEON

622

the years of 2002 to 2006, Patients with a hospital

LOS > 24 hours were evaluated and those with missing
serum ethanol levels on admission were excluded to
assess the role of ethanol as a risk factor for the
development of delirium. Patient variables extracted
included age, gender, ethnicity, injury mechanism,
comorbidities (cardiovascular disease, diabetes mellitus, dementia, psychiatric disease, and chronic ethanol
or illicit drug use), admission vitals, Glasgow Coma
Scale (GCS) score and toxicology results for ethanol
and illicit drugs (-1- or -) on admission, description of
injuries (traumatic brain injury, intrathoracic and/or
intra-abdominal injury, pelvic fracture, and extremity
fracture). Injury Severity Seore (ISS), type of insurance,
and outcomes (^ventilation days, ICU and hospital LOS,
and mortality).
The population was divided into two groups: those
who developed delirium and those who did not. The
International Classification of Diseases, 9th Revision,
Clinical Modification codes (ICD-9) 290,11, 290.41,
291.0, 292.81, and 293.0-1 were used to identify patients who developed delirium. In the present evaluation, ICD-9 codes for delirium were used exclusively
as a diagnostic tool.
Continuous variables were dichotomized using the
following clinically relevant cut-points: age (^ 55 vs <
55 years), systolic blood pressure (SBP) on admission
(< 90 vs > 90 mm Hg), GCS on admission (< S vs >
8), and ISS (^ 16 vs < 16), These two groups were
compared for differences in demographics, comorbidities, clinical data ,and outcomes using bivariate
analysis, x^ test was used to compare proportions, and
unpaired Student's t test was used to compare means.
For the analysis of outcomes. Analysis of Covariance
and binary logistic regression were used to adjust for
differences between the two groups.

To identify independent risk factors for the development of delirium, factors that on bivariate analysis were significant at P < 0,2, were entered in a
stepwise logistic regression model analysis. Positive
and negative predictive values were calculated to determine how well this model predicted the development of delirium. The summary data is presented as a
raw percentage or mean standard deviation. The P
values were significantly different at P < 0,05, Data
were analyzed using SPSS for Windows, version 16.0
(SPSS, Chicago, IL).
Results

During the 5-year study period, a total of 1,503,074

adult trauma patients were identified. After exclusion
of 538,242 with hospital LOS < 24 hours and 459,993
with missing serum ethanol levels on admission,
504,839 patients (49.6%) remained for analysis and
constituted the study population. Of those, 2,909
(0.6%) developed delirium and 501,930 (99.4%) did
not (Fig. 1),
Patients developing delirium were significantly
older (53,9 18.0 vs 44.8 19.7, P < 0.001), more
frequently male (72.8% vs 67.4%, P < 0,001), more
likely to sustain thermal injuries (2.3% V5 1.1%, P <
0,001) and, amongst blunt injuries, falls were most
common (41.5% vs 25.4%, P < 0.001). Patients developing delirium had more comorbidities including
chronic ethanol use (19,1% vs 4,5%, P < 0,001) and
cardiovascular diseases (21,5% vs 12,2%, P < 0,001). On
admission, patients developing delirium were more
likely to be intoxicated with ethanol (55.4% vs 26.5%,
P < 0,001) and illicit drugs (18,6% vs 14,3%, P < 0,001).
Patients developing delirium were more severely injured
with higher ISS (12.2 10.2 vs 11.6 10.7, P = 0.005)

Age 18 years
1,503,074
(80.7%)

NTDB

2002 - 2006
1,861,779

Exclusioti

_J

n=998,235
HLOS<24 h, n=538,242
0 No ethanol levels, n=459,993

Study Popuiation
504,839
(49.6%)

Delirium
2,909
(0.6%)

EiG. 1. Study outline.

Vol, 77

May 2011

No Delirium
501,930
(99.4%)

No. 5

RISK FACTORS FOR DELIRIUM IN TRAUMA PATIENTS

and were more likely to have a SBP < 90 mm Hg on

admission (9.1% vs 5.9%, P < 0.001). Patients developing delirium were also more likely to be uninsured (17.8% vs 0.9%, P < 0.001) and to have
Medicare (24.8% vs 13.9%, P < 0.001). Comparison of
demographics, comorbidities, and clinical data between groups is presented in Table 1.
As shown in Fig. 2, the incidence of delirium varied
widely according to ethanol status on admission as
well as chronic history of ethanol use; from 0.2 per
cent for patients negative for ethanol to 2.8 per cent for
those with chronic history of ethanol use admitted with
posidve ethanol levels.
After adjusfing for differences in age, gender, injury
mechanism, comorbidities, intubation requirements,
SBP, GCS, and toxicology status on admission, ISS,

Branoo et al.

623

associated injuries, and type of insurance between

groups, padents who developed delirium had significanfiy longer vendladon days (2.5 35.1 vs 0.7 10.4,
P < 0.001), ICU LOS (4.0 8.3 vs 2.2 8.3, P <
0.001), and hospital LOS (13.0 12.4 vs 8.3 12.6,
P < 0.001). There was no significant difference in
mortahty (3.4% vs 2.8%, P = 0.735) between the two
groups (Table 2). A stepwise logisfic regression model
identified lack of insurance, the presence of ethanol on
admission, chronic ethanol use, ICU admission, age s
55 years, burns. Medicare insurance, falls, and history
of cardiovascular disease as independent risk factors
for the development of delirium (Table 3).
To determine how well our model predicted delirium, we calculated the positive predictive values and
negative predictive values when no risk factors for

TABLE 1. Demographics, Comorbidities, and Clinical Data Between Patient Croups

Demographics
Age (y), mean SD
Age > 55
Male
Caucasian
Penetrating
Burn
Blunt
MVA
Fall
Comorbidities
Chronic ethanol use
Chronic drug use
Cardiovascular disease
Diabetes mellitus
Dementia
Psychiatric disease

Total
(n = 504,839)

Delirium
(n = 2909)

No Delirium
(n = 501,930)

44.9 19.7
28.9% (145,909)
67.4% (340,402)
64.4% (325,154)
10.8% (54,738)
1.1% (5,634)
87.0% (439,376)
45.2% (228,336)
25.5% (128,917)

53.9 18.0
43.2% (1,257)
72.8% (2,119)
76.5% (2,224)
8.1% (235)
2.3% (66)
88.2% (2,567)
33.5% (974)
41.5% (1,207)

44.8 19.7
28.8% (144,652)
67.4% (338,283)
64.3% (322,930)
10.9% (54,503)
1.1% (5,568)
87.0% (436,809)
45.3% (227,362)
25.4% (127,710)

<O.OOI*
<0.001*
<0.001*
<0.001*
<O.OOI*
<O.OOI*
<0.051
<0.001*
<0.001*

4.6%
2.5%
12.3%
3.9%
0.9%
3.9%

19.1%
5.6%
21.5%
4.9%
1.2%
5.4%

4.5%
2.5%
12.2%
3.9%
0.9%
3.9%

<0.001*
<0.001*
<0.001*
0.007*
0.064*
<0.001*

(23,222)
(12,832)
(61,864)
(19,925)
(4,602)
(19,809)

(555)
(163)
(624)
(143)
(36)
(156)

(22,667)
(12,669)
(61,240)
(19,782)
(4,566)
(19,653)

i~^linipnl Hta

Positive for ethanol on admission

Positive for drug on admission
Intubated on admission
SBP on admission, mean SD
SBP on admission < 90 mmHg
GCS on admission < 8
ISS, mean SD
ISS > 16
Traumatic brain injury
Intrathoraeic and/or
intra-abdominal injury
Pelvic fracture
Extremity fracture
Uninsured
Medicare
Medicaid

Othert

26.6% (134,479)
14.4% (72,535)
5.3% (26,835)
133.3 + 35.2
5.9% (28,525)
23.2% (104,915)
11.6+ 10.8
29.9% (150,055)
14.9% (75,299)
14.1% (71,313)

55.4% (1,613)
.18.6% (541)
9.3% (270)
131.1 +41.3
9.1% (226)
22.5% (567)
12.2 + 10.2
32.5% (941)
11.9% (345)
12.4% (362)

26.5% (132,866)
14.3% (71,994)
5.3% (26,565)
133.3 + 35.1
5.9% (28,299)
23.2% (104,348)
11.6+ 10.7
29.9% (149,114)
14.9% (74,954)
14.1% (70,951)

<0.001*
<0.001*
<0.001*
0.002*
<0.001*
0.394
0.005*
0.003*
<O.OOI*
0.009*

4.8%
19.2%
1.0%
14.0%
7.2%
73.5%

3.9%
15.1%
17.8%
24.8%
8.9%
46.6%

4.8%
19.2%
0.9%
13.9%
7.2%
73.6%

0.016*
<0.001*
<0.001*
<0.001*
0.001*
<0.001*

(24,411)
(96,833)
(5,128)
(70,702)
(36,442)
(370,867)

(113)
(438)
(518)
(721)
(258)
(1,355)

(24,298)
(96,395)
(4,610)
(69,981)
(36,184)
(369,512)

The P values for categorical variables were derived from x test; P values for continuous variables were derived from unpaired
Student's / test.
* P values are significantly different (P < 0.05).
t Other includes self-pay, commercial plan, automobile. Blue Cross/Shield, worker's compensation, managed care organization, and government/military insurances.
SD, standard deviation; MVA, motor-vehicle accident.

624

THE AMERICAN SURGEON

May 2011

Vol. 77

2.8%

- Ethanol on
admission

+ Ethanol on
admission

No chronic ethanol

Chronic ethanol use

+ Ethanol on
admission and chronic
use

FIG. 2. Incidence of delirium according to admission ethanol status and chronic ethanol use.

TABLE 2. Outcomes Between Patient Groups

Venttlation days, mean SD

ICU LOS, mean SD
Hospital LOS, mean SD

Total
(n = 504,839)

Delirium
(n = 2909)

No Delirium
(n = 501,930)

0.7 10.7
2.2 8.3
8.4 12.6

2.5 35.1
4.0 8.3
13.0 12.4

0.7 10.4
2.2 8.3
8.3 12.6

Adjusted Mean
Difference
(95% CI)

Adjusted P

1.8(1.3,2.3)
<0.001*
1.8(1.4,2.0)
<0.001*
4.6 (4.2, 5.2)
<0.001*
Adjusted OR
Adjusted P
(95% CI)
(189,268)
1.8 (1.6, 1.9)
<0.001*
(80,236)
1.7(1.5, 1.8)
<0.001*
(14,006)
1.1 (0.8, 1.3)
0.735
ICU LOS, and hospital LOS; and from binary

43 .3% (190,722)
ICU admission (%)
58.3% (1,454) 43.2%
20 .9% (80,887)
Ventilated (%)
30.4% (651)
20.9%
2 .8% (14,106)
Mortality (%)
3.4% (100)
2.8%
The P values were derived from Analysis of Covariance for ventilation days,
logistic regression for mortality and ICU and ventilation requirements.
The P values were obtained after adjustment for age, gender, mechanism of injury, comorbidities, intubation requirements, SBP
and GCS on admission, ethanol and drug levels on admission, ISS, associated injuries, and type of insurance.
* P values are significantly different {P < 0.05).
CI, conftdence interval; SD, standard deviation; OR, odds ratio.

TABLE

3. Risk Factors for Development of Delirium

Adjusted OR
R'
Variable
Delirium
(95% Cl)
Adjusted P
1
Uninsured
10.1%
0.07
52.6 (38.5, 71.4)
<0.001*
2
+ Ethanol on admission
1.2%
0.04
4.9(4.1,5.1)
<0.00] *
3
Chronic ethanol use
2.4%
0.03
2.3(2.1,2.6)
<0.00]*
4
ICU admission
0.8%
0.03
2.1 (1.9,2.3)
<0.001*
5
Age > 55 years
0.9%
0.02
1.9(1.7,2.1)
<0.001*
6
Burns
1.2%
0.01
1.8(1.3,2.5)
<0.001*
7
Medicare
1.0%
0.01
2.7(1.1, 1.9)
<0.001*
8
Falls
0.9%
0.01
1.7(1.5, 1.9)
<0.001*
9
Cardiovascular disease
1.0%
0.01
1.3(1.2,2.6)
<0.001*
Variables entered in the regression: age s 55 years, gender, mechanism of injury, comorbidities, intubation requirements, SBP <
90 mm Hg and GCS < 8 on admission, ethanol and drug levels on admission, ISS > 16, traumatic brain injury, intrathoracic and/or
intra-abdominal injury, pelvic fracture, extremity fracture, type of insurance, and need for ICU admission.
A total of 389,971 (77.2%) subjects with complete data were included in the model.
* P values are significantly different {P < 0.05).
OR, odds ratio; Cl, confidence interval.
Step

delirium were present, when > 2, > 3, ^ 4, and > 5

risk factors were present. When no risk faetors were
present, < 0.001 per eent of these patients developed
delirium. When s 5 factors were present, 71.4 per cent
of patients developed delirium (Table 4).

Discussion
The development of delirium is associated with
significant morbidity. Previous studies have documented increased complications and a prolonged LOS

No. 5

RISK FACTORS FOR DELIRIUM IN TRAUMA PATIENTS

Branco et at.

625

TABLE 4.

Model Prediction for Delirium Development According to the Presence and Number of Risk Factors
Risk Factors Present
Events
Delirium
PPV (95% CI)
NPV (95% CI)

No (none)
42/91,835
<0.001%
0.00 (0.00, 0.00)
0.99 (0.99, 0.99)
> 2 factors
365/1,750
20.9%
0.29 (0.25, 0.42)
0.99 (0.98, 0.99)
s 3 factors
55/171
32.2%
0.32 (0.26, 0.40)
0.98 (0.97, 0.99)
S: 4 factors
68/160
42.5%
0.43 (0.39, 0.46)
0.99 (0.98, 0.99)
5/7
> 5 factors
71.4%
0.72 (0.35, 0.92)
0.99 (0.99, 0.99)
Risk factors: lack of insurance, positive ethanol on admission, chronic ethanol use, ICU admission, age > 55 years, burns.
Medicare insurance, falls, and cardiovascular disease.
PPV, positive predictive values; NPV, negative predictive values.

when delirium develops, resuldng in increased hospital Uninsured padents may be more susceptible to chronic
costs. In a study published in the late 1990s, Spies and and/or acute ethanol use.^- ' Two recent publications
colleagues' evaluated a cohort of 213 cridcally ill by Rosen et al." and Salim et al.'^ also using the
medical padents, 39 of whom developed delirium. NTDB demonstrated worse overall outcomes among
These patients had an increased incidence of pneu- uninsured padents after trauma. The authors hypothemonia, sepsis, and a prolonged ICU stay by approxi- sized three possible reasons for such difference: 1)
mately 8 days when compared with those who did not Lack of insurance may be associated with delays in
develop delirium.' Similarly, Marik and Mohedin^ treatment, 2) Uninsured patients may receive a differprospecdvely collected 200 ethanol-dependent pa- ent standard of care than insured patients, and 3) Undents, of which 20 per cent developed delirium. These insured padents may possess a lower rate of health
padents had their ICU stay increased by 4 days and literacy stemming from or resuldng in less effective
total hospital charges increased by $10,000.^ Moreover, communieadon with their trauma care providers." Aldelirium may also be confused with a wide spectrum of though the present study does not allow for an analysis
diseases, in particular sepsis, complicadng the diagnosis of the causative factors underlying this strong relationand treatment of these conditions.^
ship between the lack of insurance and development of
In the present study, we used the NTDB, the largest delirium, this represents an area for possible intervennational trauma database from over 900 United States tion and further research into this association.
trauma centers. The aim was to idendfy padents who
This study also provides quantitative support to the
developed delirium and to determine the independent association between ethanol and delirium. The presrisk factors for its development. We included adult ence of ethanol on admission increased the risk of
trauma patients for whom ethanol levels on admission developing delirium by 4-fold. If chronic ethanol use
were available (positive or negative) as a history of was present, this risk increased by 12-fold. Although
ethanol use has been shown to significantly impact the delirium was first described as early as 1787, its asdevelopment of delirium.^- '' ^ We identified 2,909 sociation to ethanol was not established until the mid
padents (0.6% of the inidal study populadon) who 1900s.'3 Ethanol use is highly prevalent amongst indeveloped delirium. After stepwise logistic regression jured patients being evaluated at a trauma center. It is
analysis, nine independent risk factors were idendfied: esdmated that a quarter of padents admitted to urban
1) lack of insurance, 2) the presence of ethanol on hospitals are posidve for ethanol.^ To date, few studies
admission, 3) chronic ethanol use, 4) ICU admission, have evaluated this association after trauma. In 2002,
5) age > 55 years, 6) bums, 7) Medicare insurance, 8) Lukan and colleagues'' reviewed all trauma patients
falls, and 9) previous history of cardiovascular disease. admitted to the University of Louisville Hospital
When no risk factors were present, only 42 patients tesdng positive for ethanol; 6 per cent of them deout of 91,835 (< 0.001%) developed delirium. The veloped delirium. When patients who developed denegative predictive value was close to 100 per cent. On lirium were compared with those who did not, patients
the other hand, if five or more of the above risk factors who developed delirium were significantly older
were present, 72 per cent of patients developed de- (age > 40), more likely to be Caucasian and to have
lirium. Although these results will require further pro- sustained thermal injuries. These patients had a 3-fold
specdve validadon, they may aid in the idendficadon of higher risk of developing delirium. Two years later, the
the at-risk padent cohort allowing more aggressive same group applied multivariable analysis to a cohort
monitoring and rapid treatment once idendfied.
of 265 trauma patients. The presence of a positive
Lack of insurance was the strongest predictor for the admission blood alcohol level, elevated mean corpusdevelopment of delirium in our model. It increased the cular volume, and age greater than 45 years were
risk of developing delirium by over 50-fold. This identified as predictors of delirium. Positive admission
finding may be an indicator of socioeconomic status. blood alcohol, in particular, was associated with a

626

THE AMERICAN SURGEON

May 2011

Vol. 77

6-fold adjusted odds rafio of developing delirium. The and infection. Despite these limitations, this study proauthors concluded that alcohol disorders may have vides epidemiologic data on the risk factors for the
played an important role in the development of de- development of delirium in adult patients assessed at
trauma centers across the United States.
lirium in this populafion.^
In summary, the incidence of delirium in this trauma
In addition to ethanol, several other factors have also
patient
cohort was 0.6 per cent. Nine independent risk
been shown to infiuence the development of delirium.
factors
for the development of delirium were identiInjury severity, blood loss, and other acute events assofied:
1)
lack of insurance, 2) presence of ethanol on
ciated with autonomie hyperactivity are likely to lower
admission,
3) chronic ethanol use, 4) ICU admission,
the threshold for the development of delirium. Age, nu5)
age
^
55
years, 6) burns, 7) Medicare insurance, 8)
tritional status, and preexisting medical comorbidities are
falls,
and
9)
previous
history of cardiovascular disease.
also likely to infiuence the development of delirium as
This
data
may
be
helpful
in designing interventions to
well. Einally, medical management, including electrolyte
prevent
delirium.
imbalances that may occur during inifial resuscitafion or
ICU course may also influence the development of delirium.'"* These risk factors have been validated in the
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