CLINICAL INVESTIGATION

Acute Kidney Injury in Traumatic Brain Injury

Patients: Results From the Collaborative
European NeuroTrauma Effectiveness
Research in Traumatic Brain Injury Study
Chiara Robba, PhD1
OBJECTIVES: Acute kidney injury is frequent in polytrauma patients, and
Erika Banzato, MS2,3
it is associated with increased mortality and extended hospital length of
Paola Rebora, PhD2
stay. However, the specific prevalence of acute kidney injury after trau-
matic brain injury is less recognized. The present study aims to describe Carolina Iaquaniello, MD2
the occurrence rate, risk factors, timing, and association with outcome of Chao-Yuan Huang, MS4
acute kidney injury in a large cohort of traumatic brain injury patients. Eveline J. A. Wiegers, PhD5

DESIGN: The Collaborative European NeuroTrauma Effectiveness Geert Meyfroidt, MD4

Research in Traumatic Brain Injury is a multicenter, prospective observa- Giuseppe Citerio, MD2,6;
tional, longitudinal, cohort study. for The CENTER-TBI ICU
Participants and Investigators
SETTING: Sixty-five ICUs across Europe.
PATIENTS: For the present study, we selected 4,509 traumatic brain in-
jury patients with an ICU length of stay greater than 72 hours and with at
least two serum creatinine values during the first 7 days of ICU stay.
MEASUREMENTS AND MAIN RESULTS: We classified acute kidney
injury in three stages according to the Kidney Disease Improving Global
Outcome criteria: acute kidney injury stage 1 equals to serum creatinine
× 1.5–1.9 times from baseline or an increase greater than or equal to 0.3
mg/dL in 48 hours; acute kidney injury stage 2 equals to serum creatinine
× 2–2.9 times baseline; acute kidney injury stage 3 equals to serum creati-
nine × three times baseline or greater than or equal to 4 mg/dL or need for
renal replacement therapy. Standard reporting techniques were used to re-
port incidences. A multivariable Cox regression analysis was performed to
model the cause-specific hazard of acute kidney injury and its association
with the long-term outcome. We included a total of 1,262 patients. The
occurrence rate of acute kidney injury during the first week was as follows:
acute kidney injury stage 1 equals to 8% (n = 100), acute kidney injury
stage 2 equals to 1% (n = 14), and acute kidney injury stage 3 equals to
3% (n = 36). Acute kidney injury occurred early after ICU admission, with
a median of 2 days (interquartile range 1–4 d). Renal history (hazard ratio =
2.48; 95% CI, 1.39–4.43; p = 0.002), insulin-dependent diabetes (hazard
ratio = 2.52; 95% CI, 1.22–5.197; p = 0.012), hypernatremia (hazard
ratio = 1.88; 95% CI, 1.31–2.71; p = 0.001), and osmotic therapy admin-
istration (hazard ratio = 2.08; 95% CI, 1.45–2.99; p < 0.001) were sig-
nificantly associated with the risk of developing acute kidney injury. Acute Copyright © 2020 by the Society of
kidney injury was also associated with an increased ICU length of stay Critical Care Medicine and Wolters
and with a higher probability of 6 months unfavorable Extended Glasgow Kluwer Health, Inc. All Rights Reserved.
Outcome Scale and mortality. DOI: 10.1097/CCM.0000000000004673

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Robba et al
CONCLUSIONS: Acute kidney injury after trau-
matic brain injury is an early phenomenon, affecting
about one in 10 patients. Its occurrence nega-
tively impacts mortality and neurologic outcome at
6 months. Osmotic therapy use during ICU stay
could be a modifiable risk factor.
KEY WORDS: acute kidney injury; kidney failure;
osmotic diuretics; traumatic brain injury
BACKGROUND
Acute kidney injury (AKI) is a complex disorder, com-
mon in critically ill patients and with high mortality
rates (1–3). Case series and reviews on AKI in trauma
patients show a vast difference in the reported occur-
rence rate, ranging from 13% up to 50% (4) probably
due to the different case mix reported. A recent meta-
analysis including 24 observational studies comprising
25,182 patients (5) found that AKI occurred in 24%
of trauma cases admitted to the ICU, 10% of which
needed continuous renal replacement therapy (CRRT)
(6). However, the quality of the studies included in this
meta-analysis was overall moderate, and study hetero-
geneity was substantial. Although the actual prevalence
of AKI in general trauma patients is still debated, there
are no definitive data on the prevalence and risk factors
for AKI in the specific subpopulation traumatic brain
injury (TBI).
The present study was therefore designed to assess
the occurrence rate and timing of AKI, the inde-
pendent risk factors associated with AKI development,
and the association between AKI and patients’ out-
come in a large cohort of TBI patients prospectively
enrolled in the Collaborative European NeuroTrauma
Effectiveness Research in TBI (CENTER-TBI) study.
METHODS
The CENTER-TBI core study is a prospective, multi-
center, observational, longitudinal cohort study (7)
involving 4,509 patients from 65 centers across Europe
(ClinicalTrials.gov registration NCT02210221) be-
tween 2014 and 2017 (8). We conducted a preplanned
analysis of the CENTER-TBI study (study plan no
157), which was approved by the CENTER-TBI pro-
posal review committee (https://www.center-tbi.eu/
data/approved-proposals). This substudy fulfills the
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Strengthening the Reporting of Observational Studies
in Epidemiology reporting guidelines (www.strobe-
statement.org) (in the additional file 1, Supplemental
Digital Content 1, http://links.lww.com/CCM/F923).
Ethical approval was obtained for each recruiting
site according to national and international standards.
The list of sites, Ethical Committees, approval num-
bers, and approval dates can be found on the website:
https://www.center-tbi.eu/project/ethical-approval.
Clinical data were collected using a custom web-
based electronic case report form (eCRF) (QuesGen
systems Inc, San Francisco, CA).
Data regarding the preinjury patients’ characteristics
(demographics, comorbidities, socioeconomic situation,
education, medications, and medical history), injury de-
scription, Injury Severity Score (ISS), ASA physical status
classification, prehospital and hospital care, as well as neu-
roimaging repositories and information on the outcome,
were collected. The data were cleaned and fully deiden-
tified, creating a database for access by researchers (the
“Neurobot” system); each data label included a link to the
relevant entry in the data dictionary as well as to details of
the eCRF design of the label. For this study, we extracted
the data from the CENTER-TBI database Version 2.0.
Inclusion and Exclusion Criteria
Patients from the CENTER-TBI database were in-
cluded if they fulfilled the following criteria:
• admission to an ICU within 24 hours from TBI;
• ICU length of stay (LOS) greater than 72 hours; and
• at least two measurements of serum creatinine (SCr) in the
first 7 days.
Patients were excluded when:
• they were not in the ICU stratum of CENTER-TBI;
• had an early (≤72 hr) mortality or discharge;
• suffered from severe pre-existing neurologic disorders; and
• had less than two SCr values during the first 7 days of ICU stay.
Clinical management was based on centers’ clinical
practice and protocols, according to the latest Brain
Trauma Foundation Guidelines (9).
Definition of AKI
The definition of AKI was based on SCr daily values
and CRRT requirements in the first seven days of
ICU stay, according to the Kidney Disease Improving
Global Outcome (KDIGO) criteria (10). Since in
the CENTER-TBI database, urine output (UO) data

were not available hourly but only daily or as general
fluid balance, the UO criterion for AKI was not used.
Therefore, we included patients with at least two mea-
surements of SCr in the first 7 days.
Patients were classified as following into four cat-
egories, according to their highest level of AKI during
the ICU stay:
• no AKI equals to absence of any of the KDIGO SCr criteria;
• AKI stage 1 (AKI1) equals to a SCr increased by 1.5 times
up to 1.9 times the baseline value or an increase in SCr equal
or higher than 0.3 mg/dL in 48 hours;
• AKI stage 2 (AKI2) equals to a SCr increased by two times
up to 2.9 times the baseline value; and
• AKI stage 3 (AKI3) equals to a SCr increased over three
times the baseline or with a value above 4 mg/dL or a pa-
tient that underwent renal replacement therapy (RRT).
In the presence of more than one value of SCr on a
single day, we considered the highest. Because a prein-
jury baseline SCr was not available, baseline SCr was
defined as the value on the day of admission. In lack of
this, we choose the first available value on day 1. Also,
in order to have an estimate of the baseline SCr values
before the trauma, we performed a sensitivity analysis
by back-calculating for each patient a preinjury SCr
value, obtained with the modification of diet in renal
disease (MDRD) formula (11), assuming a glomerular
filtration rate of 75 mL/min per 1.73 m2.
Outcomes
Patients’ functional outcome was assessed using the
Extended Glasgow Outcome Scale (GOSE) at 6 months.
Study personnel obtained all responses from patients
or from a proxy (where impaired cognitive capacity
prevented patient interview), during a face-to-face
visit, by telephone interview or by postal questionnaire
at 6 months after injury. All outcome assessors had re-
ceived training in the use of the GOSE. We evaluated
the ICU mortality and the GOSE at 6 months (coded
as “unfavorable,” if < 5 or “favorable” otherwise).
Statistical Analysis
Detailed statistical analysis methods are described in
the additional file 1 (Supplemental Digital Content,
http://links.lww.com/CCM/F923).
RESULTS
Of the 2,138 patients admitted to an ICU from the
CENTER-TBI study, 1,262 fulfilled the inclusion
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Clinical Investigation
criteria (Fig. S2, Supplemental Digital Content 1, http://
links.lww.com/CCM/F923). By using the two different
baseline values for AKI definition (first available value
of SCr and MDRD back-calculation), 1,210 patients
(96%) were classified coherently as AKI or not, and
1,185 (94%) were classified precisely in the same AKI
category (Table S1, Supplemental Digital Content 1,
http://links.lww.com/CCM/F923). Given this agree-
ment, we decided to show only the results from the
analyses based on the AKI definition applied using the
first available SCr value as the baseline.
Occurrence of AKI
One-hundred fifty patients (12%) had AKI during the
first week in ICU: 100 (8%) AKI1, 14 (1%) AKI2, and
36 (3%) AKI3. AKI occurred with a median of 2 days
(interquartile range [IQR], 1–4 d). Overall transition
probabilities of patients in the study are described
in Figure 1. Twenty-three patients required CRRT
(described in Table S2, Supplemental Digital Content 1,
http://links.lww.com/CCM/F923).
Factors Related to AKI Development
Compared with patients who never experienced AKI,
patients with AKI tended to have a higher occur-
rence of preinjury renal dysfunction (9.3% vs 3.5%;
p = 0.003) and insulin-dependent diabetes (6.4% vs 2%;
p = 0.004) (Table 1). A total of 786 patients received
intracranial pressure (ICP) monitoring. Patients
with AKI were more frequently monitored with ICP
(AKI = 107 [71.3%] vs no AKI 679 [61.1%]; p = 0.019).
Patients with AKI had a higher maximum value of
Na during the first 10 days from admission compared
with non-AKI (151.34 [sd 8.61] vs 146.67 [sd 6.12];
p < 0.001). Patients who developed AKI had also a
worse neurologic status at arrival (Glasgow Coma
Scale [GCS] and pupillary reactivity). No differences
were found regarding the type of TBI between the two
groups. Cranial surgery was performed in 500 non-
AKI patients (45.2%) versus 91 AKI patients (60.7%)
(p < 0.001). Extracranial surgery was performed in 386
(34.9%) non-AKI versus 54 (36%) AKI patients.
Compared with patients with normal kidney func-
tion, those with AKI presented more ICU complica-
tions, such as neuroworsening episodes (52% vs 30.8%;
p < 0.001) and respiratory failure (42.7% vs 31%;
p = 0.006).
Robba et al

of fluids, sedation, barbitu-

rates, and osmotic therapy
received).
The predictive Cox
model for the occurrence of
AKI is presented in Table 2.
Renal history (hazard
ratio [HR] = 2.41; 95% CI,
1.35–4.32; p = 0.003),
insulin-dependent dia-
betes (HR = 2.64; 95%
CI, 1.27–5.46; p = 0.009),
pupillary reactivity, osmo
tic therapy administra-
tion (HR = 1.79; 95% CI,
1.24–2.61; p < 0.002), and
the occurrence of Na2+
values above 150 mEq/L in
the first 3 days from admis-
sion (HR = 1.88; 95% CI,
Figure 1. Overall transition probabilities of patients in the study in all the six following states: ICU
admission, death or discharge without an acute kidney injury (AKI) episode, AKI, death or discharge after 1.31–2.71; p = 0.001) were
an AKI episode. In the x-axis, the time since admission, whereas in the y-axis, the probabilities to be in found to be significantly as-
any of the states below the curve, as transition probabilities are stacked. The area covered by the gray sociated with the risk of de-
shaded states (AKI, death, or discharge after AKI) represents the cumulative occurrence rate of AKI. veloping AKI. Interestingly,
the administration of os-
The percentage of patients who received analge- motic therapy increased the risk of AKI by two times,
sics was lower in the AKI group (77.1% vs 85.4%; as well as a history of renal disease and the presence
p = 0.014) (Table S3a, Supplemental Digital Content 1, of insulin-dependent diabetes. Furthermore, patients
http://links.lww.com/CCM/F923). Also, we did not find with a more serious neurologic condition (i.e., with one
any difference in the use of contrast for radiological ex- or both pupillary unreactive) had a hazard of AKI two
amination in the first 3 days since admission between the times higher than other patients. We report the results
two groups (AKI: 19.7% vs no AKI: 17.9%; p = 0.371). of the predictive Cox model of AKI for the complete-
Patients with AKI were significantly more often treated case data in Table S5a (Supplemental Digital Content
with osmotic therapy, as for mannitol (26% vs 15.3%; p = 1, http://links.lww.com/CCM/F923). Finally, Table
0.002) and hypertonic saline (34% vs 25.2%; p = 0.029), S5b (Supplemental Digital Content 1, http://links.
as well as with colloids and vasopressors during the first lww.com/CCM/F923) reports the same model esti-
3 days since admission (Table S3b, Supplemental Digital mation with mannitol and HS added separately. These
Content 1, http://links.lww.com/CCM/F923). results show an HR equals to 2.13, 95% CI 1.38–3.3,
There were vast differences in the occurrence of AKI p value equals to 0.001 for mannitol and HR equals to
and the characteristics of the patients among different 1.47, 95% CI 0.98–2.2, p value equals to 0.06 for HS.
countries (Fig. 2), ranging from 34.2% to 3.6%. In order
to understand these differences, we grouped countries Association Between AKI and Patients’
Outcomes
with an occurrence rate above and under 10%, respec-
tively (Table S4, Supplemental Digital Content 1, http:// Patients with AKI had an increased ICU LOS compared
links.lww.com/CCM/F923). Patients in countries with a with no AKI patients (15 d [IQR 8–24 d] vs 12 d [IQR:
higher occurrence rate of AKI (> 10%) were older, with 6–20 d]; p = 0.002). As shown in Figure S2 (Supplemental
lower GCS at arrival and preinjury status, and had a sig- Digital Content 1, http://links.lww.com/CCM/F923), AKI
nificantly higher therapy intensity level in ICU (in terms was associated with higher mortality (log-rank test p <
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 Clinical Investigation

TABLE 1.
Baseline Characteristics of the Study Population, Taking in Consideration Acute Kidney
Injury Diagnosis
Baseline Patients' Characteristics No AKI AKI p Missing (%)

N 1,112 150
Age, median (IQR) 48 (29–63) 53 (32.5–68) 0.136 0.0
Injury Severity Score, median (IQR) 34 (25–43) 34 (25–43) 0.138 0.0
Sex = male, n (%) 822 (73.9) 117 (78.0) 0.330 0.0
Preinjury ASA physical status classification, n (%) 0.154 4.4
Normal healthy patient, n (%) 625 (58.7) 73 (51.8)
Patient with mild systemic disease, n (%) 337 (31.6) 48 (34.0)
Patient with severe systemic disease, n (%) 103 (9.7) 20 (14.2)
Renal history, n (%) 37 (3.5) 13 (9.3) 0.003 5.2
Cardiovascular history, n (%) 278 (26.1) 47 (33.6) 0.077 4.5
Hepatic history, n (%) 38 (3.6) 5 (3.6) 1.000 5.3
Previous traumatic brain injury, n (%) 74 (7.5) 7 (5.4) 0.497 11.1
Alcohol intoxication, n (%) 292 (30.0) 36 (27.7) 0.659 12.6
Drugs intoxication, n (%) 48 (5.5) 10 (8.8) 0.225 21.9
Pupillary reactivity (%) < 0.001 5.0
Both reacting, n (%) 872 (82.3) 91 (65.5)
Both unreacting, n (%) 117 (11.0) 29 (20.9)
One reacting, n (%) 71 (6.7) 19 (13.7)
Hypoxia, n (%) 156 (15.0) 22 (16.2) 0.809 6.7
Hypotension, n (%) 159 (15.2) 21 (15.1) 1.000 6.0
Any major extracranial injury, n (%) 689 (62.0) 94 (62.7) 0.938 0.0
Abdomen/pelvis trauma, n (%) 239 (21.5) 22 (14.7) 0.067 0.0
Total GCS at arrival ≤ 8 (%) 608 (57.6) 97 (67.8) 0.025 5.0
Motor GCS at arrival (%) 0.031 1.8
None, n (%) 387 (35.4) 65 (44.5)
Abnormal extension, n (%) 39 (3.6) 11 (7.5)
Abnormal flexion, n (%) 59 (5.4) 8 (5.5)
Normal flexion/withdrawal, n (%) 102 (9.3) 12 (8.2)
Localizes to pain, n (%) 238 (21.8) 24 (16.4)
Obeys command, n (%) 268 (24.5) 26 (17.8)
Insulin-dependent diabetes, n (%) 21 (2.0) 9 (6.4) 0.004 4.9
Noninsulin-dependent diabetes, n (%) 42 (4.0) 7 (5.0) 0.737 4.9
AKI = acute kidney injury, GCS = Glasgow Coma Scale, IQR = interquartile range.

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Robba et al

DISCUSSION
This study is the most ex-
tensive prospective obser-
vational study investigating
AKI in a prospective cohort
of severe TBI patients admit-
ted to the ICU. AKI affects
the 12% of TBI patients,
occurs early in the ICU stay,
but only rarely requires RRT.
AKI development is related
to previous renal history,
insulin-dependent diabetes,
the severity of TBI, and the
administration of osmotic
therapy. Finally, AKI has a
substantial impact on ICU
mortality and mortality and
neurologic outcome at 6
months.

Occurrence Rate of
AKI in TBI
In our cohort, AKI occurs
Figure 2. Occurrence of acute kidney injury (AKI) per country. AT = Austria, BE = Belgium, DE = in 12% of TBI and during
Germany, ES = Spain, FI = Finland, FR = France, IT = Italy, NL = The Netherlands, NO = Norway, the first days from admis-
SE = Sweden, UK = United Kingdom. sion. A recent meta-anal-
ysis (5) found that AKI
0.001) comparing with no AKI patients, with a survival at occurred in 24% of trauma patients admitted to the
6 months of 0.601 (95% CI, 0.525–0.688) and 0.84 (95% ICU. When it develops, AKI is usually staged as AKI
CI, 0.818–0.863), respectively. 1 and 2, according to the KDIGO criteria. We also
AKI occurrence was associated with increased described a wide range of incidences among coun-
ICU and overall mortality and with a higher prob- tries. These differences, confirmed by previous litera-
ability of unfavorable 6 months GOSE also after ture (3–5), can be related to the heterogeneity of the
adjusting for the variables in the IMPACT model (12) trauma population and to the differences in the ICU
(Table 3). management.
To be noted, AKI increased the hazard of ICU
mortality (HR = 2.25, 95% CI, 1.51–3.37; p < 0.001) Factors Related to AKI Development
and overall mortality (HR = 2.4; 95% CI, 1.73–3.31;
p < 0.001) by almost 2.5 times, compared with no AKI Prediction of AKI development is challenging, al-
patients. Furthermore, patients who developed AKI had a though it could be potentially useful to detect patients
higher probability of an unfavorable neurologic outcome at risk. The study from Harrois et al (4) identified sev-
(GOSE < 5) at 6 months. The odds ratio is three times eral independent risk factors for AKI, including the
higher compared with no AKI patients (odds ratio = 3.04; ISS, prehospital hemodynamic variables, the pres-
95% CI, 1.87–4.92; p < 0.001). Please refer to Table S6 ence of renal trauma, as well as the patients’ blood
(Supplemental Digital Content 1, http://links.lww.com/ lactate levels and rhabdomyolysis severity. However,
CCM/F923) for the complete-case analysis results. this retrospective study included all-causes trauma

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 Clinical Investigation

TABLE 2.
Results of the Predictive Cox Model of Acute Kidney Injury (Any Stage)
Acute Kidney
n = 1,262 Injury (%) Hazard Ratio Lower 0.95 Upper 0.95 p

Age 1.008 0.999 1.017 0.083

Pupillary reactivity
  Both reactive 9.1 1.00
  Both unreactive 19.9 1.886 1.198 2.971 0.006
  One reactive 21.1 1.772 1.005 2.077 0.031
Motor Glasgow Coma Scale
 None 14.4 1.168 0.771 1.769 0.463
  Abnormal extension 22 1.561 0.785 3.104 0.203
  Abnormal flexion 11.9 0.954 0.436 2.089 0.907
  Normal flexion/withdrawal 10.5 0.861 0.445 1.666 0.656
 Localize/obeys 9 1.00
Renal history
 Yes 26 2.415 1.350 4.321 0.003
 No 11 1.00
Insulin-dependent diabetes
 Yes 20.3 2.637 1.273 5.462 0.009
 No 11.1 1.00
Osmotic therapy administration
 Yes 12.8 1.797 1.236 2.614 0.002
 No 11.5 1.00
Na+ ≥ 150 (first 3 d)
 Yes 20.5 1.884 1.308 2.713 0.001
 No 9.6 1.00
The number of events, hazard ratios, and CIs are reported along with the associated p. The model estimation has been carried out after
the multiple imputation procedure.

patients (not only TBI) and presents several limita-
tions, since it misses data about comorbidities and
blood tests as well as data on the administration of
nephrotoxic agents, such as colloids and antibiotics.
In our cohort, factors related to the development
of AKI include a preinjury history of renal disease
and insulin-dependent diabetes (thus suggesting the
importance of pre-injury patients’ status) as well as
pupillary abnormalities (likely related to more severe
neurologic conditions at arrival). Of note, the occur-
rence of hypernatremia in the first 3 days from admis-
sion increased significantly the risk of AKI. Similarly,
Kumar et al (13) found that in subarachnoid hemor-
rhage patients, for each 1 mEq/L increase in the daily
serum sodium, the hazard of developing AKI increases
by 5.4 % (95% CI, 1.4–9.7).

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Robba et al

TABLE 3.
Effect of Acute Kidney Injury on Outcomes After Adjusting for the International Mission
for Prognosis and Analysis of Clinical trials in Traumatic Brain Injury Variablesa
AKI, HR or
No. of No. of OR(Reference Lower Upper
Outcomes Patients Events No AKI) 0.95 0.95 P

ICU mortality (%) 1,262 137 2.252 1.507 3.366 < 0.001
Mortality (%) 1,262 224 2.394 1.731 3.311 < 0.001
Unfavorable Extended Glasgow 1,106 556 3.036 1.873 4.921 < 0.001
Outcome Scale at 6 mo (%)
AKI = acute kidney injury, HR = hazard ratio, OR = odds ratio.
We estimated a Cox regression model with AKI as a time-dependent variable for the ICU mortality and the general mortality, whereas we
used logistic regression to predict the unfavorable outcome at 6 mo. We defined a Extended Glasgow Outcome Scale score of < 5 as
“unfavorable.” The number of events, HR, OR, and CIs are reported along with the associated p. The model estimation has been carried
out after the multiple imputation procedure.
a
International Mission for Prognosis and Analysis of Clinical trials in Traumatic brain injury variables are as follows: age, motor Glasgow
Outcome Scale at arrival, pupillary reactivity, variables describing the secondary insults (hypoxia and hypertension), the CT scan
characteristics (as the Marshall CT classification, the presence of a traumatic subarachnoid hemorrhage, or an epidural hematoma), the
presence of any extracranial injury.

Also, we found that AKI occurrence is associated
with the administration of osmotic therapy. These latter
points are of extreme clinical importance and represent
a pivotal result from our study; in fact, despite clinical
management of TBI patients was based on centers’ clin-
ical practice, mannitol and HS are the currently used
osmotic drugs for the management of intracranial hy-
pertension (9). Experimental data suggest that mannitol
provides beneficial effects against contrast-induced
nephropathy (14) and can have renal-protective effect
(15, 16). However, clinical data are discordant on the
protective effects of mannitol on kidney function (17),
as administration of high-dose mannitol has shown to
induce extensive renal proximal tubular vacuolization
and acute renal failure (18, 19). The effect of HS on
kidney function is unclear as well (20). A greater rel-
ative change of Na+, the presence of initial hypernatre-
mia, and a slower subsequent fall in serum sodium and
chloride (21) are known risk factors for AKI that might
be influenced by HS (22, 23). The association between
osmotic therapy and AKI found in our cohort suggests
that osmotic therapy should be used with caution for
the treatment of elevated ICP in multitrauma patients.
Surprisingly, we did not find any correlation with
pre-hospital hypotension episodes nor with the pres-
ence of any major extracranial injury. This result could
be due to the evolving characteristics of the TBI pop-
ulation, which over the last decades is involving older
subjects with a higher occurrence of accidental falls,
and to the reduction of road traffic accidents (8).
Effects on Outcome
Several authors suggested that after a trauma, the pres-
ence of organ dysfunction, especially renal, has an
essential impact on the LOS and mortality (24–29);
furthermore, a meta-analysis suggests that patients
with AKI have a 6.0 days (4.0–7.9 d) longer ICU LOS
and increased risk of death (relative risk 3.4 [2.1–5.7])
compared with no AKI patients (28).
Corral et al (30) observed an increase of 6.17-fold
risk of death in TBI patients who develop severe AKI.
We found that AKI, even though uncommon, can
have a substantial impact on patients’ outcome, with an
adverse effect on ICU and overall mortality and the un-
favorable neurologic outcome at 6 months. Therefore,
kidney injury after trauma should be promptly identi-
fied and managed, and risk factors associated with AKI
development should be early recognized.
Limitations
This study has several limitations that deserve to be men-
tioned. First, according to KDIGO, the SCr definition
of AKI is based on relative increases as compared to the
baseline values. Unfortunately, in our database, there was
no SCr value from before the beginning of critical illness

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and admission to ICU, which would have represented
a patient’s true baseline SCr. The use of admission SCr
could have induced bias, as some patients might already
have a kidney insult upon admission. However, to over-
come this limitation, we also estimated the basal SCr using
the MDRD method, which demonstrated similar values
compared with our methods (Table S1, Supplemental
Digital Content 1, http://links.lww.com/CCM/F923, co-
herence between the two methods of 96%).
Second, regarding the definition of AKI, the lack
of information regarding the hourly UO forced us to
use just the SCr criteria, which might have led to an
underestimation of the prevalence of these categories
in our population. Third, there are some missing data
(especially regarding laboratory results, such as lactate,
details on complications such as brain herniation, or
dose or way of drugs administration, that is, inotropes,
that are related to the fact that assessing AKI was not
the primary aim of CENTER-TBI. However, multiple
imputations have been used to overcome this issue.
Finally, this study is aimed to evaluate the association
among factors, but this does not imply causality.
CONCLUSIONS
Acute kidney occurs in 12% of cases after TBI, but se-
vere AKI is rare. When it occurs, it develops early in
the first days from ICU admission. Some of the factors
related to the risk of developing AKI after trauma are
not modifiable, e.g., the presence of previous renal his-
tory or insulin-dependent diabetes, and the severity of
TBI. Others, as the administration of osmotic therapy
and strict sodium management can be modified.
Despite the low prevalence, development of AKI is
associated with ICU and overall mortality and neuro-
logic outcome. Further studies should aim at exploring
therapeutic interventions able to prevent or treat AKI
in this cohort of patients.
1 Department of Anaesthesia and Intensive Care Policlinico
San Martino IRCCS for Oncology and Neuroscience,
Genova, Italy.
2 Department of Medicine and Surgery, University of Milano -
Bicocca, Monza, Italy.
3 Department of Statistical Sciences, University of Padova,
Padua, Italy.
4 Department and Laboratory of Intensive Care Medicine,
University Hospitals Leuven and KU Leuven, Leuven,
Belgium.
Critical Care Medicine www.ccmjournal.org      9
Copyright © 2020 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.
Clinical Investigation
5 Department of Public Health, Erasmus University Medical
Center, Rotterdam, the Netherlands.
6 Neurointensive care unit, Department of Emergency and
Urgency, San Gerardo Hospital, ASST- Monza, Monza, Italy.
Dr. Robba participated in the conception of the work, data analysis
and interpretation, article drafting, critical revision of the article,
and final approval of the version to be published. Drs. Banzato,
Iaquaniello, and Wiegers participated in data analysis and inter-
pretation, article drafting, critical revision of the article, and final
approval of the version to be published. Dr. Rebora participated
and supervised in data analysis and interpretation, article draft-
ing, critical revision of the article, and final approval of the version
to be published. Dr. Huang involved in calculation of the serum
creatinine (SCr) estimated using the modification of diet in renal
disease (MDRD) method, critical revision of the article, and final
approval of the version to be published. Dr. Meyfroidt involved
in calculation of the SCr estimated using the MDRD method,
participation in data interpretation, critical revision of the article,
final approval of the version to be published. Dr. Citerio involved
in conception of the work, supervision of the data collection, par-
ticipation in data analysis and interpretation, drafting the article,
critical revision of the article, and final approval of the version to
be published. Dr. Citerio is guarantor of the entire article. The
Collaborative European NeuroTrauma Effectiveness Research in
Traumatic Brain Injury participants and investigators (nonauthor
contributors) contributed to participation in the data collection.
Supplemental digital content is available for this article. Direct
URL citations appear in the printed text and are provided in the
HTML and PDF versions of this article on the journal’s website
(http://journals.lww.com/ccmjournal).
Data used in the preparation of this article were obtained
in the context of The Collaborative European NeuroTrauma
Effectiveness Research in Traumatic Brain Injury (registered at
ClinicalTrials.gov NCT02210221), a large collaborative pro-
ject, supported by the Framework 7 program of the European
Union (602150). Supported, in part, by the Hannelore Kohl
Stiftung (Germany), by OneMind (United States), and by Integra
LifeSciences Corporation (United States).
Dr. Meyfroidt’s institution received funding from Research
Foundation, Flanders, KULeuven Research Grant (C2), and
Codman; he received funding from other consulting and advisory
boards. Dr. Citerio is Editor-in-Chief of Intensive Care Medicine,
and he reports grants, personal fees as Speakers’ Bureau Member
and Advisory Board Member from Integra and Neuroptics; per-
sonal fees from Nestle and UCB Pharma, all outside of the sub-
mitted work. The remaining authors have disclosed that they do
not have any potential conflicts of interest.
The Medical Ethics Committees of each participating center
approved the CENTER-TBI study, and informed consent was
obtained according to local regulations. The list of sites, Ethical
Committees, approval numbers and approval dates can be found
on the website: https://www.center-tbi.eu/project/ethical-approval.
The data supporting the findings in the study are available upon
reasonable request from the senior author (G.C.) and are stored
at https://center-tbi.incf.org/_5cf8e3d1c3b0d43708ebef42. Data
Robba et al
used for the definition of the acute kidney injury stage are stored
at https://center-tbi.incf.org/_5d1dc708f9753b41d06d7806 and
at https://center-tbi.incf.org/_5db08eb0ec506a3052ee469c,
respectively for what concerned the creatinine and the urine
output values. Imaging data can be found at https://center-tbi.
incf.org/_5cf4dbd0560bb01102b6b28e, data on vitals values at
https://center-tbi.incf.org/_5cf4dce9560bb01102b6b28f, data
regarding medications can be found at https://center-tbi.incf.
org/_5cf4de0d560bb01102b6b291, whereas daily therapy in-
tensity level data are stored at https://center-tbi.incf.org/_5d30277
15. Wu X, Zhang W, Ren H, et al: Diuretics associated acute
1462c403213f35e35.
For information regarding this article, E-mail: giuseppe.citerio@
unimib.it
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APPENDIX
The CENTER-TBI ICU Participants and Investigators
group members: Cecilia Åkerlund, Department of
Physiology and Pharmacology, Section of Perioperative
Medicine and Intensive Care, Karolinska Institutet,
Stockholm, Sweden; Krisztina Amrein, János
Szentágothai Research Centre, University of Pécs, Pécs,
Hungary; Nada Andelic, Division of Surgery and
Clinical Neuroscience, Department of Physical
Medicine and Rehabilitation, Oslo University Hospital
and University of Oslo, Oslo, Norway; Lasse Andreassen,
Department of Neurosurgery, University Hospital
Northern Norway, Tromso, Norway; Audny Anke,
Department of Physical Medicine and Rehabilitation,
University Hospital Northern Norway, Tromso,
Norway; Gérard Audibert, Department of
Anesthesiology & Intensive Care, University Hospital
Nancy, Nancy, France; Philippe Azouvi, Raymond
Poincare Hospital, Assistance Publique – Hopitaux de
Paris, Paris, France; Maria Luisa Azzolini, Department
of Anesthesiology & Intensive Care, S Raffaele
University Hospital, Milan, Italy; Ronald Bartels,
Department of Neurosurgery, Radboud University
Medical Center, Nijmegen, The Netherlands; Ronny
Beer, Department of Neurology, Neurological Intensive
Care Unit, Medical University of Innsbruck, Innsbruck,
Austria; Bo-Michael Bellander, Department of
Neurosurgery & Anesthesia & intensive care medicine,
Karolinska University Hospital, Stockholm, Sweden;
Habib Benali, Anesthesie-Réanimation, Assistance
Publique – Hopitaux de Paris, Paris, France; Maurizio
Berardino, Department of Anesthesia & ICU, AOU
Città Della Salute e Della Scienza di Torino - Orthopedic
and Trauma Center, Torino, Italy; Luigi Beretta,
Department of Anesthesiology & Intensive Care, S
Raffaele University Hospital, Milan, Italy; Morten
Blaabjerg, Department of Neurology, Odense
University Hospital, Odense, Denmark; Stine Borgen
Lund, Department of Public Health and Nursing,
Faculty of Medicine and Health Sciences, Norwegian
Critical Care Medicine www.ccmjournal.org      11
Copyright © 2020 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.
Clinical Investigation
University of Science and Technology, NTNU,
Trondheim, Norway; Camilla Brorsson, Department
of Surgery and Perioperative Science, Umeå University,
Umeå, Sweden; Andras Buki, Department of
Neurosurgery, Medical School, University of Pécs,
Hungary and Neurotrauma Research Group, János
Szentágothai Research Centre, University of Pécs,
Hungary; Manuel Cabeleira, Brain Physics Lab,
Division of Neurosurgery, Dept of Clinical
Neurosciences, University of Cambridge, Addenbrooke’s
Hospital, Cambridge, United Kingdom; Alessio
Caccioppola, Emiliana Calappi, Neuro ICU,
Fondazione IRCCS Cà Granda Ospedale Maggiore
Policlinico, Milan, Italy; Maria Rosa Calvi, Department
of Anesthesiology & Intensive Care, S Raffaele
University Hospital, Milan, Italy; Peter Cameron,
ANZIC Research Centre, Monash University,
Department of Epidemiology and Preventive Medicine,
Melbourne, VIC, Australia; Guillermo Carbayo
Lozano, Department of Neurosurgery, Hospital of
Cruces, Bilbao, Spain; Marco Carbonara, Neuro ICU,
Fondazione IRCCS Cà Granda Ospedale Maggiore
Policlinico, Milan, Italy; Ana M. Castaño-León,
Department of Neurosurgery, Hospital Universitario
12 de Octubre, Madrid, Spain; Giorgio Chevallard,
Arturo Chieregato, NeuroIntensive Care, Niguarda
Hospital, Milan, Italy; Giuseppe Citerio, School of
Medicine and Surgery, Università Milano Bicocca,
Milano, Italy; NeuroIntensive Care, ASST di Monza,
Monza, Italy; Mark Coburn, Department of
Anaesthesiology, University Hospital of Aachen,
Aachen, Germany; Jonathan Coles, Department of
Anesthesia & Neurointensive Care, Cambridge
University Hospital NHS Foundation Trust,
Cambridge, United Kingdom; Jamie D. Cooper, School
of Public Health & PM, Monash University and The
Alfred Hospital, Melbourne, VIC, Australia; Marta
Correia, Radiology/MRI department, MRC Cognition,
and Brain Sciences Unit, Cambridge, United Kingdom;
Endre Czeiter, Department of Neurosurgery, Medical
School, University of Pécs, Hungary and Neurotrauma
Research Group, János Szentágothai Research Centre,
University of Pécs, Hungary; Marek Czosnyka, Brain
Physics Lab, Division of Neurosurgery, Dept of Clinical
Neurosciences, University of Cambridge,
Addenbrooke’s Hospital, Cambridge, United Kingdom;
Claire Dahyot-Fizelier, Intensive Care Unit, CHU
Poitiers, Poitiers, France; Véronique DeKeyser,
Robba et al
Department of Neurosurgery, Antwerp University
Hospital and University of Antwerp, Edegem, Belgium;
Vincent Degos, Anesthesie-Réanimation, Assistance
Publique – Hopitaux de Paris, Paris, France; Francesco
Della Corte, Department of Anesthesia & Intensive
Care, Maggiore Della Carità Hospital, Novara, Italy;
Hugo den Boogert, Department of Neurosurgery,
Radboud University Medical Center, Nijmegen, The
Netherlands; Bart Depreitere, Department of
Neurosurgery, University Hospitals Leuven, Leuven,
Belgium; Dula Dilvesi, Department of Neurosurgery,
Clinical center of Vojvodina, Faculty of Medicine,
University of Novi Sad, Novi Sad, Serbia; Abhishek
Dixit, Division of Anaesthesia, University of
Cambridge, Addenbrooke’s Hospital, Cambridge,
United Kingdom; Jens Dreier, Center for Stroke
Research Berlin, Charité – Universitätsmedizin Berlin,
corporate member of Freie Universität Berlin,
Humboldt-Universität zu Berlin, and Berlin Institute
of Health, Berlin, Germany; Guy-Loup Dulière,
Intensive Care Unit, CHR Citadelle, Liège, Belgium;
Ari Ercole, Division of Anaesthesia, University of
Cambridge, Addenbrooke’s Hospital, Cambridge,
United Kingdom; Erzsébet Ezer, Department of
Anaesthesiology and Intensive Therapy, University of
Pécs, Pécs, Hungary; Martin Fabricius, Departments of
Neurology, Clinical Neurophysiology and
Neuroanesthesiology, Region Hovedstaden
Rigshospitalet, Copenhagen, Denmark; Kelly Foks,
Department of Neurology, Erasmus MC, Rotterdam,
the Netherlands; Shirin Frisvold, Department of
Anesthesiology and Intensive care, University Hospital
Northern Norway, Tromso, Norway; Alex Furmanov,
Department of Neurosurgery, Hadassah-Hebrew
University Medical center, Jerusalem, Israel; Damien
Galanaud, Anesthesie-Réanimation, Assistance
Publique – Hopitaux de Paris, Paris, France; Dashiell
Gantner, ANZIC Research Centre, Monash University,
Department of Epidemiology and Preventive Medicine,
Melbourne, VIC, Australia; Alexandre Ghuysen,
Emergency Department, CHU, Liège, Belgium; Lelde
Giga, Neurosurgery clinic, Pauls Stradins Clinical
University Hospital, Riga, Latvia; Jagos Golubovic,
Department of Neurosurgery, Clinical center of
Vojvodina, Faculty of Medicine, University of Novi
Sad, Novi Sad, Serbia; Pedro A. Gomez, Department of
Neurosurgery, Hospital Universitario 12 de Octubre,
Madrid, Spain; Francesca Grossi, Department of
12      www.ccmjournal.org XXX 2020 • Volume XX • Number XXX
Copyright © 2020 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.
Anesthesia & Intensive Care, Maggiore Della Carità
Hospital, Novara, Italy; Deepak Gupta, Department of
Neurosurgery, Neurosciences Centre & JPN Apex
trauma centre, All India Institute of Medical Sciences,
New Delhi-110029, India; Iain Haitsma, Department
of Neurosurgery, Erasmus MC, Rotterdam, the
Netherlands; Raimund Helbok, Department of
Neurology, Neurological Intensive Care Unit, Medical
University of Innsbruck, Innsbruck, Austria;
Eirik Helseth, Department of Neurosurgery, Oslo
University Hospital, Oslo, Norway; Peter J. Hutchinson,
Division of Neurosurgery, Department of Clinical
Neurosciences, Addenbrooke’s Hospital & University
of Cambridge, Cambridge, United Kingdom; Stefan
Jankowski, Neurointensive Care, Sheffield Teaching
Hospitals NHS Foundation Trust, Sheffield, United
Kingdom; Mladen Karan, Department of Neurosurgery,
Clinical center of Vojvodina, Faculty of Medicine,
University of Novi Sad, Novi Sad, Serbia;
Angelos G. Kolias, Division of Neurosurgery,
Department of Clinical Neurosciences, Addenbrooke’s
Hospital & University of Cambridge, Cambridge,
United Kingdom; Daniel Kondziella, Departments of
Neurology, Clinical Neurophysiology and
Neuroanesthesiology, Region Hovedstaden
Rigshospitalet, Copenhagen, Denmark; Evgenios
Koraropoulos, Division of Anaesthesia, University of
Cambridge, Addenbrooke’s Hospital, Cambridge,
United Kingdom; Lars-Owe Koskinen, Department of
Clinical Neuroscience, Neurosurgery, Umeå University,
Umeå, Sweden; Noémi Kovács, Hungarian Brain
Research Program - Grant No. KTIA_13_NAP-A-II/8,
University of Pécs, Pécs, Hungary; Ana Kowark,
Department of Anaesthesiology, University Hospital
of Aachen, Aachen, Germany; Alfonso Lagares,
Department of Neurosurgery, Hospital Universitario
12 de Octubre, Madrid, Spain; Steven Laureys,
Cyclotron Research Center, University of Liège, Liège,
Belgium; Aurelie Lejeune, Department of
Anesthesiology-Intensive Care, Lille University
Hospital, Lille, France; Roger Lightfoot, Department
of Anesthesiology & Intensive Care, University
Hospitals Southhampton NHS Trust, Southhampton,
United Kingdom; Hester Lingsma, Department of
Public Health, Erasmus Medical Center-University
Medical Center, Rotterdam, The Netherlands;
AndrewI.R. Maas, Department of Neurosurgery,
Antwerp University Hospital and University of

Antwerp, Edegem, Belgium; Alex Manara, Intensive
Care Unit, Southmead Hospital, Bristol, Bristol, United
Kingdom; Costanza Martino, Department of
Anesthesia & Intensive Care, M. Bufalini Hospital,
Cesena, Italy; Hugues Maréchal, Intensive Care Unit,
CHR Citadelle, Liège, Belgium; Julia Mattern,
Department of Neurosurgery, University Hospital
Heidelberg, Heidelberg, Germany; Catherine
McMahon, Department of Neurosurgery, The Walton
centre NHS Foundation Trust, Liverpool, United
Kingdom; David Menon, Division of Anaesthesia,
University of Cambridge, Addenbrooke’s Hospital,
Cambridge, United Kingdom; Tomas Menovsky,
Department of Neurosurgery, Antwerp University
Hospital and University of Antwerp, Edegem, Belgium;
Davide Mulazzi, Neuro ICU, Fondazione IRCCS Cà
Granda Ospedale Maggiore Policlinico, Milan, Italy;
Visakh Muraleedharan, Karolinska Institutet, INCF
International Neuroinformatics Coordinating Facility,
Stockholm, Sweden; Lynnette Murray, ANZIC
Research Centre, Monash University, Department of
Epidemiology and Preventive Medicine, Melbourne,
VIC, Australia; Nandesh Nair, Department of
Neurosurgery, Antwerp University Hospital and
University of Antwerp, Edegem, Belgium, Ancuta
Negru, Department of Neurosurgery, Emergency
County Hospital Timisoara, Timisoara, Romania;
David Nelson, Department of Physiology and
Pharmacology, Section of Perioperative Medicine and
Intensive Care, Karolinska Institutet, Stockholm,
Sweden; Virginia Newcombe, Division of Anaesthesia,
University of Cambridge, Addenbrooke’s Hospital,
Cambridge, United Kingdom; Quentin Noirhomme,
Cyclotron Research Center, University of Liège, Liège,
Belgium; József Nyirádi, János Szentágothai Research
Centre, University of Pécs, Pécs, Hungary;
Fabrizio Ortolano, Neuro ICU, Fondazione IRCCS Cà
Granda Ospedale Maggiore Policlinico, Milan, Italy;
Jean-François Payen, Department of Anesthesiology &
Intensive Care, University Hospital of Grenoble,
Grenoble, France; Vincent Perlbarg, Anesthesie-
Réanimation, Assistance Publique – Hopitaux de Paris,
Paris, France; Paolo Persona, Department of Anesthesia
& Intensive Care, Azienda Ospedaliera Università di
Padova, Padova, Italy; Wilco Peul, Deptartment of
Neurosurgery, Leiden University Medical Center,
Leiden, The Netherlands, and Deptartment of
Neurosurgery, Medical Center Haaglanden, The
Critical Care Medicine www.ccmjournal.org      13
Copyright © 2020 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.
Clinical Investigation
Hague, The Netherlands; Anna Piippo-Karjalainen,
Department of Neurosurgery, Helsinki University
Central Hospital, Helsinki, Finland; Horia Ples,
Department of Neurosurgery, Emergency County
Hospital Timisoara, Timisoara, Romania; Inigo
Pomposo, Department of Neurosurgery, Hospital of
Cruces, Bilbao, Spain; Jussi P. Posti, Division of Clinical
Neurosciences, Department of Neurosurgery and
Turku Brain Injury Centre, Turku University Hospital
and University of Turku, Turku, Finland; Louis
Puybasset, Department of Anesthesiology and Critical
Care, Pitié -Salpêtrière Teaching Hospital, Assistance
Publique, Hôpitaux de Paris, and University Pierre et
Marie Curie, Paris, France; Andreea Radoi,
Neurotraumatology and Neurosurgery Research Unit
(UNINN), Vall d’Hebron Research Institute, Barcelona,
Spain; Arminas Ragauskas, Department of
Neurosurgery, Kaunas University of technology and
Vilnius University, Vilnius, Lithuania; Rahul Raj,
Department of Neurosurgery, Helsinki University
Central Hospital, Helsinki, Finland; Jonathan Rhodes,
Department of Anaesthesia, Critical Care & Pain
Medicine NHS Lothian & University of Edinburg,
Edinburgh, United Kingdom; Sophie Richter, Division
of Anaesthesia, University of Cambridge,
Addenbrooke’s Hospital, Cambridge, United Kingdom;
Saulius Rocka, Department of Neurosurgery, Kaunas
University of technology and Vilnius University,
Vilnius, Lithuania; Cecilie Roe, Department of Physical
Medicine and Rehabilitation, Oslo University Hospital/
University of Oslo, Oslo, Norway; Olav Roise, Division
of Surgery and Clinical Neuroscience, Oslo University
Hospital, Oslo, Norway; Jeffrey V. Rosenfeld, National
Trauma Research Institute, The Alfred Hospital,
Monash University, Melbourne, Victoria, Australia;
Christina Rosenlund, Department of Neurosurgery,
Odense University Hospital, Odense, Denmark; Guy
Rosenthal, Department of Neurosurgery, Hadassah-
Hebrew University Medical center, Jerusalem, Israel;
Rolf Rossaint, Department of Anaesthesiology,
University Hospital of Aachen, Aachen, Germany;
Sandra Rossi, Department of Anesthesia & Intensive
Care, Azienda Ospedaliera Università di Padova,
Padova, Italy; Juan Sahuquillo, Neurotraumatology
and Neurosurgery Research Unit (UNINN), Vall
d’Hebron Research Institute, Barcelona, Spain; Oddrun
Sandro, Department of Anesthesiology and Intensive
Care Medicine, St.Olavs Hospital, Trondheim
Robba et al
University Hospital, Trondheim, Norway; Oliver
Sakowitz, Department of Neurosurgery, University
Hospital Heidelberg, Heidelberg, Germany; Klinik für
Neurochirurgie, Klinikum Ludwigsburg, Ludwigsburg,
Germany; Renan Sanchez-Porras, Klinik für
Neurochirurgie, Klinikum Ludwigsburg, Ludwigsburg,
Germany; Kari Schirmer-Mikalsen, Department of
Anesthesiology and Intensive Care Medicine, St.Olavs
Hospital, Trondheim University Hospital, Trondheim,
Norway; Department of Neuromedicine and
Movement Science, Norwegian University of Science
and Technology, NTNU, Trondheim, Norway;
Rico Frederik Schou, Department of Neuroanesthesia
and Neurointensive Care, Odense University Hospital,
Odense, Denmark; Peter Smielewski, Brain Physics
Lab, Division of Neurosurgery, Dept of Clinical
Neurosciences, University of Cambridge,
Addenbrooke’s Hospital, Cambridge, United Kingdom;
Abayomi Sorinola, Department of Neurosurgery,
University of Pécs, Pécs, Hungary; Emmanuel
Stamatakis, Division of Anaesthesia, University of
Cambridge, Addenbrooke’s Hospital, Cambridge,
United Kingdom; Ewout W. Steyerberg, Department of
Anesthesiology & Intensive Care, University Hospitals
Southhampton NHS Trust, Southhampton, United
Kingdom; Deptartment of Department of Biomedical
Data Sciences, Leiden University Medical Center,
Leiden, The Netherlands; Nino Stocchetti, Department
of Pathophysiology and Transplantation, Milan
University, and Neuroscience ICU, Fondazione IRCCS
Cà Granda Ospedale Maggiore Policlinico, Milano,
Italy; Nina Sundström, Department of Radiation
Sciences, Biomedical Engineering, Umeå University,
Umeå, Sweden; Riikka Takala, Perioperative Services,
Intensive Care Medicine and Pain Management, Turku
University Hospital and University of Turku, Turku,
Finland; Viktória Tamás, Department of Neurosurgery,
University of Pécs, Pécs, Hungary; Tomas Tamosuitis,
Department of Neurosurgery, Kaunas University of
Health Sciences, Kaunas, Lithuania; Olli Tenovuo,
Division of Clinical Neurosciences, Department of
Neurosurgery and Turku Brain Injury Centre, Turku
University Hospital and University of Turku, Turku,
Finland; Matt Thomas, Intensive Care Unit, Southmead
Hospital, Bristol, Bristol, United Kingdom; Dick
Tibboel, Intensive Care and Department of Pediatric
Surgery, Erasmus Medical Center, Sophia Children’s
Hospital, Rotterdam, The Netherlands; Christos Tolias,
14      www.ccmjournal.org XXX 2020 • Volume XX • Number XXX
Copyright © 2020 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.
Department of Neurosurgery, Kings College London,
London, United Kingdom; Tony Trapani, ANZIC
Research Centre, Monash University, Department of
Epidemiology and Preventive Medicine, Melbourne,
VIC, Australia; CristinaMaria Tudora, Department of
Neurosurgery, Emergency County Hospital Timisoara,
Timisoara, Romania; Peter Vajkoczy, Neurologie,
Neurochirurgie und Psychiatrie, Charité –
Universitätsmedizin Berlin, Berlin, Germany; Shirley
Vallance, ANZIC Research Centre, Monash University,
Department of Epidemiology and Preventive Medicine,
Melbourne, VIC, Australia; Egils Valeinis,
Neurosurgery clinic, Pauls Stradins Clinical University
Hospital, Riga, Latvia; Zoltán Vámos, Department of
Anaesthesiology and Intensive Therapy, University of
Pécs, Pécs, Hungary; Gregory Van der Steen,
Department of Neurosurgery, Antwerp University
Hospital and University of Antwerp, Edegem, Belgium;
Jeroen T. J. M. van Dijck, Thomas A. van Essen,
Department of Neurosurgery, Leiden University
Medical Center, Leiden, The Netherlands, and Dept. of
Neurosurgery, Medical Center Haaglanden, The
Hague, The Netherlands; Audrey Vanhaudenhuyse,
Anesthesie-Réanimation, Assistance Publique –
Hopitaux de Paris, Paris, France; Cyclotron Research
Center, University of Liège, Liège, Belgium; Roel P. J.
van Wijk, Department of Neurosurgery, Leiden
University Medical Center, Leiden, The Netherlands,
and Dept. of Neurosurgery, Medical Center
Haaglanden, The Hague, The Netherlands; Alessia
Vargiolu, NeuroIntensive Care, ASST di Monza,
Monza, Italy; Emmanuel Vega, Department of
Anesthesiology-Intensive Care, Lille University
Hospital, Lille, France; Anne Vik, Department of
Neuromedicine and Movement Science, Norwegian
University of Science and Technology, NTNU,
Trondheim, Norway; Department of Neurosurgery,
St.Olavs Hospital, Trondheim University Hospital,
Trondheim, Norway; Rimantas Vilcinis, Department
of Neurosurgery, Charité – Universitätsmedizin Berlin,
corporate member of Freie Universität Berlin,
Humboldt-Universität zu Berlin, and Berlin Institute
of Health, Berlin, Germany; Victor Volovici,
Department of Neurosurgery, Erasmus MC,
Rotterdam, the Netherlands; Daphne Voormolen,
Department of Public Health, Erasmus Medical
Center-University Medical Center, Rotterdam, The
Netherlands; Petar Vulekovic, Department of
 Clinical Investigation

Neurosurgery, Clinical center of Vojvodina, Faculty of
Medicine, University of Novi Sad, Novi Sad, Serbia;
Guy Williams, Stefan Winzeck, Division of Anaesthesia,
University of Cambridge, Addenbrooke’s Hospital,
Cambridge, United Kingdom; Stefan Wolf, Department
of Neurosurgery, Charité – Universitätsmedizin Berlin,
corporate member of Freie Universität Berlin,
Humboldt-Universität zu Berlin, and Berlin Institute
of Health, Berlin, Germany; Alexander Younsi,
Department of Neurosurgery, University Hospital
Heidelberg, Heidelberg, Germany; Frederik A. Zeiler,
Division of Anaesthesia, University of Cambridge,
Addenbrooke’s Hospital, Cambridge, United Kingdom;
Section of Neurosurgery, Department of Surgery, Rady
Faculty of Health Sciences, University of Manitoba,
Winnipeg, MB, Canada; Agate Ziverte, Neurosurgery
clinic, Pauls Stradins Clinical University Hospital,
Riga, Latvia; Tommaso Zoerle, Neuro ICU, Fondazione
IRCCS Cà Granda Ospedale Maggiore Policlinico,
Milan, Italy.

Critical Care Medicine www.ccmjournal.org      15

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