Intensive & Critical Care Nursing xxx (xxxx) xxx

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Intensive & Critical Care Nursing

journal homepage: www.elsevier.com/iccn

Research article

Risk factors and outcomes of sepsis-associated delirium in intensive care

unit patients: A secondary data analysis
Yeunwoo Kim, Yinji Jin, Taixian Jin, Sun-Mi Lee ⇑
College of Nursing, The Catholic University of Korea, Seoul, Republic of Korea

a r t i c l e i n f o a b s t r a c t

Article history: Objective: To identify the risk factors of sepsis-associated delirium and determine their effect on inten-
Received 16 July 2018 sive care unit adult patient outcomes.
Revised 14 February 2020 Design: A secondary analysis of data from system development studies.
Accepted 19 February 2020
Setting: Korean intensive care unit patients in a university hospital who were diagnosed with sepsis.
Available online xxxx
Methods: The risk factors for sepsis-associated delirium were classified into patient factors and sepsis
clinical features and were analysed using hierarchical logistic regression analysis. Outcomes included
Keywords:
in-hospital mortality, 30-day in-hospital mortality, duration of mechanical ventilation, length of stay
Delirium
Risk factors
in the intensive care unit, length of hospital stay, total medical expenses, discharge placement, re-
Sepsis hospitalisation and visits to the emergency department after discharge.
Sepsis-associated encephalopathy Results: The risk factor for sepsis-associated delirium including patients aged 65 years, dependent
Treatment outcome activity and high nursing needs (patient factors), low level of consciousness, tachypnoea, and thrombo-
cytopaenia (clinical features of sepsis). Use of vasopressors/inotropes and albumin decreased the risk of
sepsis-associated delirium. Mechanical ventilation duration was prolonged and discharge to skilled nurs-
ing facilities was increased by sepsis-associated delirium.
Conclusions: The risk factors for sepsis-associated delirium increased as the severity of condition for
patients with sepsis increased. Early identification of risk factors associated with sepsis-associated delir-
ium may improve patient outcomes.
Ó 2020 Elsevier Ltd. All rights reserved.

Implications for clinical practice

 Older age, dependent activity, high nursing needs and low level of consciousness, tachypnoea, and thrombocytopaenia are risk fac-
tors in sepsis-associated delirium. However, albumin and use of vasopressors/inotropes reduce the risk of sepsis-associated delirium.
 The risk of sepsis-associated delirium is increased when the severity of sepsis associated organ dysfunction increases.
 Patients with sepsis-associated delirium have longer an increased number of days of mechanical ventilation and an increased rate of
discharge to skilled nursing facilities.

Introduction Schramm et al., 2012; Tsuruta and Oda, 2016). Sepsis-associated

Brain dysfunction in sepsis has been investigated with different
terminology: particularly sepsis-associated delirium (SAD) and
sepsis-associated encephalopathy (Iacobone et al., 2009;
⇑ Corresponding author at: College of Nursing, The Catholic University of Korea,
222, Banpo-daero, Seocho-gu, Seoul 06591, Republic of Korea.
E-mail address: leesunmi@catholic.ac.kr (S.-M. Lee).
encephalopathy is considered a diffuse disturbance in cerebral dys-
function caused by a systemic inflammatory response to infection
without evidence of direct central nervous system infection
(Wilson and Young, 2003). However, we use the term SAD in this
study because ‘‘delirium” is used globally in current diagnostic
manuals. The incidence rate of SAD in the intensive care unit
(ICU) is 17.7–31.5% (Anderson et al., 2016; Zhang et al., 2012).

https://doi.org/10.1016/j.iccn.2020.102844
0964-3397/Ó 2020 Elsevier Ltd. All rights reserved.

Please cite this article as: Y. Kim, Y. Jin, T. Jin et al., Risk factors and outcomes of sepsis-associated delirium in intensive care unit patients: A secondary data
analysis, Intensive & Critical Care Nursing, https://doi.org/10.1016/j.iccn.2020.102844
2 Y. Kim et al. / Intensive & Critical Care Nursing xxx (xxxx) xxx
Although the prognosis of SAD is unclear (Iacobone et al., 2009),
it is similar to that of ICU delirium (Sonneville et al., 2013). SAD
increases the duration of mechanical ventilation, ICU length of stay
(Zhang et al., 2012) and mortality (Nguyen et al., 2014; Zhang et al.,
2012). Given that sepsis is associated with ongoing cognitive
impairment and functional disability (Iwashyna et al., 2010), it is
highly likely to induce neuroradiological and neuropathological
problems if accompanied by SAD (Iacobone et al., 2009). However,
research on the outcomes of SAD remains limited. Despite those
negative outcomes, there is currently no treatment for SAD
(Sonneville et al., 2013; Souza-Dantas et al., 2016). Therefore, the
early detection of risk factors and providing immediate interven-
tions are important to prevent delirium and ensure patient safety
(Barr et al., 2013). Yet, few studies have reported cortisol
(Nguyen et al., 2014), heart rate, Glasgow coma scale (GCS), blood
lactate, platelet, albumin (Zhang et al., 2012) and Sequential Organ
Failure Assessment (SOFA) score (Nguyen et al., 2016) as the risk
factors of SAD. Most results only showed a correlation between
these factors and SAD. Therefore, identifying the risk factors and
outcomes of SAD would enable early detection and prompt inter-
ventions to enable a better outcome, which could lead to a more
efficient method using an automated system based on the elec-
tronic health records (EHRs) (Back et al., 2016; Moon et al., 2018).
Methods
Objectives
The purpose of this study was to identify the risk factors of SAD
in terms of patient factors and clinical features of sepsis and its
effects on patient outcomes in ICU patients.
Study design and setting
This study was a secondary data analysis from risk assessment
system development studies of delirium (Moon et al., 2018) and
sepsis (Back et al., 2016). This study was carried out in a 1355-
bed university hospital in Seoul, Republic of Korea. Specifically,
data were collected in the medical and surgical ICU and these ICUs
had 44 beds in total.
Ethical approval
Ethical approval was given by the institute review board of the
Catholic University of Korea (IRB-CUMC09U091, KC13RISI0066)
and Seoul St. Mary’s hospital (KC15RNS10255).
Data sources/measurement
This study was conducted on the data, which is from primary
studies, extracted from the Electronic Healthcare Records (EHR)
of patients admitted to the ICU from September 2009 to June
2015. Data corresponding to the participants of this study and
research variables were extracted and analysed. The research data
of the delirium group was extracted on the day before the develop-
ment of delirium. Among the dataset, delirium assessment results
were addressed by the Confusion Assessment Method for Intensive
Care Unit (CAM-ICU) (Ely et al., 2001).
Participant selection
The participants included patients who were diagnosed with
sepsis according to the American College of Chest Physicians (ACCP)
and the Society of Critical Care Medicine (SCCM) conference consen-
sus definition. Using the Sepsis-1 criteria, sepsis was defined as the
Please cite this article as: Y. Kim, Y. Jin, T. Jin et al., Risk factors and outcomes of sepsis-associated delirium in intensive care unit patients: A secondary data
analysis, Intensive & Critical Care Nursing, https://doi.org/10.1016/j.iccn.2020.102844
state of having both diagnosed infection and the presence of sys-
temic inflammatory response syndrome (SIRS) criteria (Levy et al.,
2003). The Sepsis-1 criteria was used due to data being collected
prior to the publication of the Sepsis-3 criteria. There were several
exclusion criteria: 1) Patients aged <18 years, and an ICU length of
stay (LOS) <24 hrs; 2) patients with severe visual defects or auditory
defects, for whom the CAM-ICU could not be used; 3) patients
whose continuous Richmond agitation sedation scale (RASS) scores
were 4 or 5; and 4) patients for whom performing an assessment
was difficult because they had suddenly fallen critically ill and had
to undergo acute treatment such as cardiopulmonary resuscitation
or had refused assessment. Participants with CAM-ICU positive
results were assigned to the delirium group, and those with nega-
tive results were assigned to the non-delirium group.
Variables
Risk factors for SAD
A total of 112 variables related to the risk factors for SAD (51
patient factors and 61 clinical features of sepsis) were selected from
the research data (Supplementary Material 1). The patient factors
included demographic characteristics and clinical characteristics,
such as nursing needs and nutritional status. Nursing needs indi-
cated the score converted by the necessity of nursing intervention;
the higher the nursing needs, the higher the condition severity.
The clinical features of sepsis were selected according to the
diagnostic criteria for sepsis, which largely consists of five domains
in the Sepsis-1 (Levy et al., 2003). Because there is no specific
method for sepsis diagnosis, it is diagnosed based on signs, symp-
toms and clinical laboratory results (Kim and Lee, 2013). The gen-
eral features included nutritional status (Holder et al., 2016; van
Vught et al., 2016) and the use of sedatives/analgesics. The inflam-
matory features included inflammation-related blood laboratory
results (Schrag et al., 2012; Yang et al., 2016) and the use of antibi-
otics. The haemodynamic features included vital signs (Brown
et al., 2016; Kenzaka et al., 2012) and organ dysfunction included
the history of respiratory support and respiratory markers
(Devran et al., 2012; Mohamed et al., 2017), coagulation biomark-
ers (Azkárate et al., 2016; Mohamed et al., 2017), liver function
profiles (Wira et al., 2014), mental status (Davydow et al., 2012;
Iwashyna et al., 2010), kidney function parameters (de Castilho
et al., 2017; Katayama et al., 2017) and the use of vasopressors/ino-
tropes. In this study, low level of consciousness (LOC) indicates
drowsiness or stupor. The severity features included Acute Physiol-
ogy and Chronic Health Evaluation Ⅱ (APACHE-Ⅱ) score (Mohamed
et al., 2017). The SOFA score was not included because the primary
study lacked a SOFA score (Devran et al., 2012; Oh et al., 2017;
Yang et al., 2016). To overcome this deficit, this study included
variables that corresponded to each factor of the SOFA using the
Sepsis-1 framework (Table 1).
Patient outcomes variables
In total, the following nine outcome variables were selected: in-
hospital mortality, 30-day in-hospital mortality, duration of
mechanical ventilation, ICU LOS, hospital LOS, total medical
expense, discharge placement, re-hospitalisation and visits to the
emergency department (ED) after discharge (Table 1). The opera-
tional definition of patient outcome variables is presented in, Sup-
plementary Material 2.
Statistical analysis
Data were analysed using Statistical Analysis Software (SAS)
version 9.2. Normally distributed continuous variables were
 Y. Kim et al. / Intensive & Critical Care Nursing xxx (xxxx) xxx 3

Table 1 Demographic and clinical characteristics

Data extraction scheme.

Domain Hierarchy Contents Number of The mean age of the delirium group was 72.07 years, which was
items higher than that of the non-delirium group (t = 4.94, p < .0001)
Risk factors Patient factors Demographic 25 (Table 2). The rate of medical ICU (v2 = 6.58, p = .010) was higher
of SAD characteristics in the delirium group than in the non-delirium group.
Clinical characteristics 26
Clinical features General area 17
of sepsis Infalammatory area 8 Risk factors of SAD by hierarchical logistic regression model
Haemodynamic area 4
Organ dysfunction area 27 Twenty-two factors associated with the risk factors for SAD
Severity area 5
were selected through the four-stage selection process. Eight of
Outcomes of Outcomes In-hospital mortality (%) 9
SAD 30-day in-hospital these were patient factors: age, activity, feeding through a gas-
mortality (%) trointestinal (GI) tube, nursing needs, admission via ED, diagnosis
Duration of mechanical for respiratory disease, operation history and endotracheal tube
ventilation (days)
use. There were fourteen clinical features of sepsis: LOC, use of
ICU LOS (days)
Hospital LOS (days)
vasopressors/inotropes, heart rate, respiration rate, body tempera-
Total medical expense ture, white blood cell (WBC), C-reactive protein (CRP), platelet, cre-
(KRW) atinine, daily urine output, total bilirubin, glucose, albumin and
Discharge placement APACHE-Ⅱ score.
Re-hospitalisation
Hierarchical logistic regression analysis was performed on the
Visits to the ED after
discharge risk factors of SAD in the order of patient factors (Model 1) and
Total 121 clinical features of sepsis (Model 2) (Table 3). This model had
SAD: sepsis- associated delirium, ICU: intensive care unit, LOS: length of stay, KRW: C-statistics of 0.91, DX 2 45.84 and Nagelkerke R2 of 0.62, indicating
Korean Won (Korean currency), Discharge placement: locations to which the the model fitness. For the patient factors (Model 1), the risk of SAD
was increased in participants aged 65 years (OR = 3.18; 95%
analysed using the mean with standard deviation (±) and correla- CI = 1.51, 6.69), with dependent activity (OR = 6.21, 95%
tion, and categorical variables were analysed using the frequency CI = 2.74, 14.09), and with higher nursing needs (OR = 4.54, 95%
and percentage. The risk factors of SAD were selected from 112 CI = 2.02, 10.18). Of the clinical features of sepsis (Model 2), the risk
variables via the following process; 1) variables with incidence or of SAD was increased in participants with low LOC (OR = 3.77,
distribution 10% were excluded; 2) univariate analyses (t-test, 95% CI = 1.01, 14.00), respiratory rate 22/min (OR = 4.00,
v2 -test) were performed with each variable, and variables were 95% CI = 1.49, 10.73), and platelet count <100x103/lL (OR = 3.41,
selected if they were statistically significant at an 0.05 alpha level; 95% CI = 1.06, 10.98). However, using vasopressors/inotropes
3) when two or more variables with high correlation were selected, (OR = 0.28, 95% CI = 0.09, 0.85) and a higher albumin level
we chose one variable (seven variables were removed in total) and (OR = 0.05, 95% CI = 0.01, 0.45) decreased the risk of sepsis-
4) variables that were not statistically significant were included if associated delirium.
they were considered important and related to SAD identified in
previous studies. Twelve variables were added in total (Supple- Outcomes of Sepsis-associated delirium
mentary Material 3).
The delirium risk factors of sepsis patients were classified into The delirium group had a longer mean duration of mechanical
two hierarchies and were assessed using hierarchical logistic ventilation (t = 2.17, p = .032) and a higher rate of discharge to
regression analysis (twenty-two variables) by putting these hierar- skilled nursing facilities (v2 = 8.67, p = .003). The mean duration
chies in the following order: patient factors (eight variables), and of mechanical ventilation was extended by 0.99 days (p = .046)
clinical features of sepsis (fourteen variables). Odds ratios (ORs) and the rate of discharge to skilled nursing facilities was increased
and 95% confidence intervals (95% CIs) were calculated in each 4.21-fold (OR = 4.21, 95% CI = 1.34, 13.20, p = .014) due to SAD
model. To show the fitness of logistic model, we used C statistics, (Table 4).
model v2 , and Nagelkerke R2 .
Regarding the patient outcomes of sepsis due to delirium,
Discussion
in-hospital mortality, discharge placement, re-hospitalisation and
visits to the ED after discharge were analysed by multiple logistic
Our current study indicates that age 65 years, dependent
regression 30-day in-hospital mortality was analysed by Cox-
activity, higher nursing needs, a reduced LOC, tachypnoea, and
proportional hazard regression and duration of mechanical ventila-
thrombocytopaenia were independently associated with the devel-
tion, ICU LOS hospital LOS and total medical expenses were anal-
opment of SAD. We found that the risk of SAD was decreased by
ysed by multiple linear regression. These regression analyses
use of vasopressors/inotropes and a higher albumin level. In this
were performed using age, gender, activity, body mass index
study, most of the selected risk factors for SAD were found to be
(BMI), admission via ED, operation, and APACHE-II score as
associated with higher sepsis severity; patients with greater nurs-
adjusted variables.
ing needs were at a higher risk of SAD, which may be because they
often accompany increased sepsis severity and delirium risk fac-
Results tors caused by severe organ dysfunction.
In the current study, the risk of SAD was decreased among
Patients patients with vasopressors/inotropes. Other investigations have
also reported a lower risk of delirium among patients receiving
In total, 804 patients (18 years) had a diagnosis of sepsis and vasopressors/inotropes (Lahariya et al., 2014). This supports the
629 were excluded from the study (See Fig. 1). The final sample findings of Smith et al. (2016) who reported lower blood pressure
comprised of 175 patients, 107 in the SAD group and 68 in the requiring inotropes causes reduction of cerebral perfusion and
non-SAD group. thereby increasing the risk of delirium (Smith et al., 2016).

Please cite this article as: Y. Kim, Y. Jin, T. Jin et al., Risk factors and outcomes of sepsis-associated delirium in intensive care unit patients: A secondary data
analysis, Intensive & Critical Care Nursing, https://doi.org/10.1016/j.iccn.2020.102844
4 Y. Kim et al. / Intensive & Critical Care Nursing xxx (xxxx) xxx

Fig. 1. Particpat selection flow.

Table 2
Demographic and clinical characteristics (N = 175).

Variables Value SAD (n = 107) Non-SAD (n = 68) v2 /t p

n (%) or Mean
Age (year) 72.07 ± 13.25 59.85 ± 17.45 4.94 <.0001
Gender Male 63 (58.88) 32 (47.06) 2.34 .126
Female 44 (41.12) 36 (52.94)
BMI (kg/m2) Overweight 14 (13.08) 12 (17.65) 1.08 .583
Underweight 17 (15.89) 8 (11.76)
Emotional status Agitation/anxiety/depression/ 36 (33.64) 20 (29.41) 0.34 .559
unconsciousness
Medical department Medical ICU 77 (71.96) 36 (52.94) 6.58 .010
System-specific disease Respiratory 70 (65.42) 38 (55.88) 1.60 .206
Cardiovascular 34 (31.78) 16 (22.53) 1.39 .239
Liver 9 (8.41) 7 (10.29) 0.18 .674
Gastrointestinal 35 (32.71) 23 (33.82) 0.02 .879
Kidney 26 (24.30) 16 (23.53) 0.01 .908
Cancer 25 (23.36) 24 (35.29) 2.94 .087
CRRT Yes 14 (13.08) 4 (5.88) 2.34 .126
Total insertion duration of catheters and other invasive 18.00 ± 32.79 11.35 ± 15.54 1.80 .073
devices
Average total number of catheters and other invasive 5.20 ± 2.65 4.63 ± 2.61 1.38 .170
devices
Transfusion history Yes 96 (89.72) 54 (79.41) 3.61 .058
Total amount of transfusion 10042.74 ± 26542.29 10372.66 ± 19362.94 0.09 .903

SAD: sepsis-associated delirium, BMI: body mass index, ICU: intensive care unit, CRRT: continuous renal replace therapy.

Furthermore, these fluctuations of blood pressure result in the set-
ting of impaired autoregulation which was found to be an influenc-
ing factor for SAD (Schramm et al., 2012). Brain injury caused by
impaired autoregulation might increase the risk of SAD because
patients with hypotension cannot maintain brain tissue perfusion.
Therefore, it may be important to assess the mental status of
patients with reduced cerebral perfusion and blood pressure. How-
ever, further study is recommended to validate this finding.
The risk of delirium was high among sepsis patients with
tachypnoea, which is a marker of organ dysfunction in sepsis
patients (Singer et al., 2016). In the early stages of sepsis, hyper-
ventilation occurs as a compensatory response to hypoxaemia for
ventilation and perfusion (VQ) mismatching (Kasper et al., 2017)
and metabolic acidosis. Hyperventilation induces cerebral vaso-
constriction causing cerebral oxygen desaturation, which is associ-
ated with cognitive decline (Suehiro and Okutai, 2011; Tang et al.,
2012). As above, cognitive impairment was found to be a risk factor
for delirium. This process by tachypnoea might affect the develop-
ment of SAD. In addition, intensive monitoring of respiratory
changes in the early stages of sepsis may be needed to prevent
the progression of sepsis and the development of SAD.
The risk of SAD was high among sepsis patients with thrombo-
cytopaenia. Thrombocytopaenia can be caused by the enhanced
activation of cytokine expression and vascular endothelial cells
(Claushuis et al., 2016); SAD has a similar mechanism (Sonneville
et al., 2013; Tsuruta and Oda, 2016). Moreover, thrombocytopaenia
is an early sign of coagulation dysfunction (Singer et al., 2016) and
may progress to disseminated intravascular coagulation (DIC) (Levi
et al., 2009) which worsens bleeding (Venkata et al., 2013). There-
fore, it may be helpful to check platelet count when assessing the
risk of SAD. Many studies have focused on exploring transfusion
and low haemoglobin levels as risk factors of delirium (Kennedy
et al., 2014; Norkienė et al., 2013). Future research is required to
determine the effects of platelet count on the risk of SAD.
The risk of delirium among sepsis patients was decreased by a
higher albumin level. As sepsis progresses, increased endothelial
permeability induces low level of albumin and also, albumin syn-
thesis in the liver decreases. Hypoalbuminaemia makes patients

Please cite this article as: Y. Kim, Y. Jin, T. Jin et al., Risk factors and outcomes of sepsis-associated delirium in intensive care unit patients: A secondary data
analysis, Intensive & Critical Care Nursing, https://doi.org/10.1016/j.iccn.2020.102844
 Y. Kim et al. / Intensive & Critical Care Nursing xxx (xxxx) xxx 5

Table 3
Hierarchical logistic regression model examining risk of Sepsis-associated delirium (N = 175).

Hierarchy Variables Value n (%) or Mean OR (95% CI)

SAD (n = 107) Non-SAD (n = 68) Model 1 Model 2
Patient factors Age 65 81 (75.70) 30 (44.12) 3.02 (1.42, 6.45)** 3.66 (1.34, 9.98)*
Activity Dependent 62 (57.94) 13 (19.12) 6.33 (2.69, 14.87)*** 14.88 (4.35, 50.91)***
Feeding through GI tube Yes 56 (52.34) 22 (32.35) 1.96 (0.74, 5.19) 2.44 (0.68, 8.74)
Nursing needs High 80 (74.77) 30 (44.12) 5.07 (2.07, 12.44)*** 4.67 (1.45, 15.04)*
Admission via ED Yes 89 (83.18) 60 (88.24) 0.60 (0.19, 1.89) 0.45 (0.12, 1.72)
Diagnosis for respiratory disease Yes 70 (65.42) 38 (55.88) 1.23 (0.56, 2.70) 1.14 (0.41, 3.21)
Operation Yes 16 (14.95) 18 (26.47) 0.48 (0.19, 1.23) 0.40 (0.12, 1.36)
Endotracheal tube Yes 44 (41.12) 18 (26.47) 0.64 (0.21, 1.98) 0.76 (0.17, 3.39)
Clinical features of sepsis LOC Low 42 (39.25) 9 (13.24) 3.77 (1.01, 14.00)*
Use of Inotropes Yes 63 (58.88) 44 (64.71) 0.28 (0.09, 0.85)*
Heart rate (/min) >90 83 (77.57) 36 (52.94) 3.02 (0.99, 9.19)
Respiratory rate (/min) 22 63 (58.88) 23 (33.82) 4.00 (1.49,10.73)**
Body temperature (°C) 36.88 ± 0.83 36.85 ± 1.05 0.90 (0.52, 1.55)
WBC (103/lL) 12.95 ± 7.41 13.20 ± 8.17 1.01 (0.95, 1.08)
C-reactive protein (mg/L) 14.17 ± 8.64 16.80 ± 8.61 0.96 (0.91, 1.02)
Platelet (103/lL) <100  103 52 (48.60) 29 (42.65) 3.41 (1.06, 10.98)*
Creatinine (mg/dL) 2.0 28 (26.17) 15 (22.06) 0.93 (0.28, 3.10)
Daily urine output (mL/day) <500 16 (14.95) 10 (14.71) 0.45 (0.10, 2.01)
Bilirubin (mg/dL) 2.40 ± 5.18 2.47 ± 3.86 0.98 (0.88, 1.08)
Glucose (mg/dL) >140 65 (60.75) 37 (54.41) 0.73 (0.25, 2.13)
Albumin (g/dL) 2.50 ± 0.00 2.67 ± 0.44 0.05 (0.01, 0.45)**
APACHE-Ⅱ 15.17 ± 5.23 13.00 ± 5.31 1.02 (0.93, 1.13)
C statistics 0.83 0.91
NagelkerkeR2 0.40 0.62
Model v2 (Dv2 ) 61.37*** 107.21 (45.84)***

OR: Odds ratio, CI: confidence interval, SAD: sepsis-associated delirium, GI: gastrointestinal, Nursing needs: score converted by the necessity of nursing intervention, High:
class Ⅴ (score 92–141), VI (score 142–999), ED: emergency department, LOC: level of consciousness, Low: drowsiness, stupor, WBC: white blood cell, APACHE-Ⅱ: Acute
Physiology and Chronic Health Evaluation-Ⅱ.
*
<0.05
**
<0.01
***
<0.001

Table 4
Impacts of Sepsis-associated delirium on patient outcomes (N = 175).

Variables SAD (n = 107) Non-SAD (n = 68) X 2 /t p OR/HR(Cl) orb

n (%) or Mean
In-hospital mortality (%)+ 45 (42.06) 22 (32.35) 1.66 .198 1.34 (0.63, 2.87)
30-day in-hospital mortality (%)++ 72 (67.29) 52 (76.47) 1.70 .193 1.73 (0.74, 4.04)
Duration of mechanical ventilation (days)+++ 1.79 ± 3.46 1.01 ± 0.98 2.17 .032 0.99*
ICU LOS (days)+++ 21.74 ± 21.25 17.65 ± 23.73 1.19 .237 3.37
Hospital LOS (days)+++ 40.85 ± 38.99 35.78 ± 33.30 0.89 .377 1.33
Total medical expense (KRW)+++ 35,797,746.80 ± 36,325,739.65 30,778,452.57 ± 31,974,085.77 0.93 .352 3,925,970
Discharge placement+
Skilled nursing facilities 24 (38.71) 6 (13.04) 8.67 .003 4.21 (1.34, 13.20)*
Home 38 (61.29) 40 (86.96)
After discharge of survivors
Re-hospitalisation+ 30 (48.39) 24 (52.17) 0.15 .697 0.78 (0.31, 1.94)
Visits to the ED after discharge+ 30 (48.39) 20 (43.48) 0.26 .613 0.71 (0.28, 1.85)

Adjusted variables: age, gender, activity, BMI, admission via ED, operation, APACHE-Ⅱ.
SAD: sepsis-associated delirium, OR: Odds ratio, HR: hazard ratio, CI: confidence interval, ICU: intensive care unit, LOS: length of stay, KRW: Korean Won (Korean currency),
Discharge placement: locations to which the patients were discharged, namely either their home or facilities that provide professional care, Skilled nursing facilities:
institutions providing skilled care including nursing home or rehabilitation centre, ED: emergency department, BMI: body mass index, APACHE-Ⅱ: Acute Physiology and
Chronic Health Evaluation-Ⅱ.
*
<0.05
+
Multiple logistic regression.
++
Cox-proportional hazard regression.
+++
Multiple linear regression.

more susceptible to organ dysfunction (Hong et al., 2017; Sun
et al., 2015). It appears that increased sepsis severity induced by
organ dysfunction creates a higher risk for SAD. It is recommended
enteral nutrition is delayed in patients with normal intravascular
volume, yet still hypotensive when administered vasopressors/ino-
tropes (Reintam Blaser et al., 2017). The decrease in albumin level
may be even more aggravated among these patients. Therefore, it
may be necessary to evaluate the patient appropriately, and then
to perform early enteral nutrition to reduce the risk of infection
(Reintam Blaser et al., 2017) and organ dysfunction; this may help
lower the risk of delirium.
Examining the effects of SAD on patient outcomes revealed that
the duration of mechanical ventilation was extended, and this is
consistent with previous reports in critically ill patients (Salluh

Please cite this article as: Y. Kim, Y. Jin, T. Jin et al., Risk factors and outcomes of sepsis-associated delirium in intensive care unit patients: A secondary data
analysis, Intensive & Critical Care Nursing, https://doi.org/10.1016/j.iccn.2020.102844
6 Y. Kim et al. / Intensive & Critical Care Nursing xxx (xxxx) xxx
et al., 2015; Zhang et al., 2013). This may be because, although
delirium increases the risk of complications such as nosocomial
pneumonia and unplanned extubation (Zhang et al., 2013), sepsis
is often accompanied by respiratory diseases. Patients with severe
sepsis may develop acute respiratory distress syndrome (ARDS),
which increases patient mortality (Kim and Hong, 2016;
Mikkelsen et al., 2013) and requires mechanical ventilation
(Rhodes et al., 2017).
The rate of discharge to skilled nursing facilities was increased
by SAD. This may be due to chronic cognitive impairment
(Pandharipande et al., 2013) and functional disability (Brummel
et al., 2014) caused by delirium, suggesting the need for rehabilita-
tion. Tertiary hospitals provide acute treatment, whilst nursing
homes and rehabilitation centres provide treatment for complica-
tions and rehabilitation. Therefore, it appears that many partici-
pants could not be discharged to their homes due to
complications of SAD and were instead discharged to other medi-
cal institutions.
Nurses have perceived delirium as a serious problem but still
need an improved identification tool, although many studies
recently have explored predictors (LaMantia et al., 2017; Xing
et al., 2017). This study’s results are expected to be the foundation
of improving an assessment system to help educate nursing staff
on SAD and provide high-quality nursing services that go beyond
the level of symptom control.
Limitations
This study had several limitations. First, the sample size was
small, as there were few sepsis patients in the primary study. Fur-
ther studies with a larger sample size are recommended to validate
our findings. Second, SOFA score was missing from the variables.
Since participants were sepsis patients, it was better to include
both APACHE- II and SOFA scores to represent the severity of sep-
sis. Third, the influence of organ dysfunction on the outcomes
could not be fully minimised. We suggest that future research
should adjust their analysis for organ dysfunction and investigate
the long-term outcomes of SAD.
Conclusion
Older age, dependent activity, high nursing needs, low LOC,
tachypnoea, and thrombocytopaenia may be useful predictors to
identify high risk of SAD. Furthermore, use of vasopressors/ino-
tropes and higher albumin levels were found to decrease the risk
of SAD. These findings suggest that the risk of SAD increases as sep-
sis severity increases due to organ dysfunction. In addition, the
duration of mechanical ventilation was extended and the rate of
discharge to skilled nursing facilities was increased due to SAD.
Identifying patients at increased risk of SAD is essential to prevent
negative outcomes.
Authorship
SL was responsible for the design of the study, analysis, inter-
pretation of data. YK made substantial contribution to the design
of the study, analysis interpretation of data and wrote the manu-
script. YJ, TJ made considerable contribution to data collection
and extraction. YK and SL revised the manuscript critically for
important intellectual content and approved final version of the
article to be admitted and have agreed to be accountable for ensur-
ing the accuracy or integrity of the work.
Please cite this article as: Y. Kim, Y. Jin, T. Jin et al., Risk factors and outcomes of sepsis-associated delirium in intensive care unit patients: A secondary data
analysis, Intensive & Critical Care Nursing, https://doi.org/10.1016/j.iccn.2020.102844
Declaration of Competing Interest
The authors declare that they have no known competing finan-
cial interests or personal relationships that could have appeared
to influence the work reported in this paper.
Acknowledement/Funding source
This study was supported by the Basic Science Research Pro-
gram of the National Research Foundation of Korea (NRF), funded
by the Ministry of Education, Science, and Technology [NRF-
2014R1A2A2A01003313].
Appendix A. Supplementary data
Supplementary data to this article can be found online at
https://doi.org/10.1016/j.iccn.2020.102844.
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