Neurocrit Care (2015) 22:184191

DOI 10.1007/s12028-014-0067-8

ORIGINAL ARTICLE

Hypernatremia is a Significant Risk Factor for Acute Kidney

Injury After Subarachnoid Hemorrhage: A Retrospective
Analysis
Avinash B. Kumar Yaping Shi Matthew S. Shotwell
Justin Richards Jesse M. Ehrenfeld

Published online: 18 September 2014

Springer Science+Business Media New York 2014

A. B. Kumar (&)
Department of Anesthesiology, Division of Critical Care
Medicine, Vanderbilt University, 1211 21st Avenue, S,
526 MAB, Nashville, TN 37212, USA
e-mail: avinash.b.kumar@vanderbilt.edu

72 h and 14 days following admission. A Cox proportional

hazards survival model with multiple time varying covariates was developed to evaluate the effect of maximum
sodium exposure on the risk of AKI. Sodium exposure was
captured as the running maximum of daily maximum
serum sodium concentration (mEq/L). Sodium exposure
was used as a surrogate for hypertonic saline therapy.
Results The final cohort of patients included 736 patients
admitted to the neuro intensive care unit between 2006 and
2012. The number of patients who developed AKI was 64
(9 %). These patients had an increased length of stay
(15.6 9.4 vs. 12.5 8.7 days). The odds of death were
more than two fold greater among patients who developed
AKI (odds ratio 2.33 95 % CI 1.27, 4.3). Sodium exposure
was significantly associated with the hazard of developing
AKI, adjusting for age, sex, preexisting renal disease,
diabetes mellitus, radiocontrast exposure, number of days
on mechanical ventilation, and admission Glasgow Coma
Scale score. For each 1 mEq/L increase in the running
maximum daily serum sodium, the hazard of developing
AKI was increased by 5.4 % (95 % CI 1.4, 9.7).
Conclusion The maximum daily sodium is a significant
risk factor for developing AKI in patients with SAH.

Y. Shi
M. S. Shotwell
Department of Biostatistics, Vanderbilt University,
1211 21st Avenue, S, 526 MAB, Nashville, TN 37212, USA
e-mail: yaping.shi@vanderbilt.edu

Keywords Hypernatremia
Acute kidney injury

Subarachnoid hemorrhage
Hyperosmolar therapy

Hypertonic saline
Serum sodium

Abstract
Background Hypertonic saline therapy is often used in
critically ill subarachnoid hemorrhage (SAH) patients for
indications ranging from control of intracranial hypertension to managing symptomatic hyponatremia. The risk
factors for developing acute kidney injury (AKI) in this
patient population are not well defined.
Specific Aim To study the role of serum sodium in developing AKI (based on the AKIN definition) in the SAH
population admitted to a large academic neurocritical care
unit.
Methods This is an IRB-approved, retrospective cohort
study of patients admitted to a tertiary neuro intensive care
unit. We included adult (age C18 years) SAH patients
admitted to the neuro intensive care unit for at least 72 h.
Development of AKI after admission to the ICU was
defined using the AKIN serum creatinine criteria between

M. S. Shotwell
e-mail: matt.shotwell@vanderbilt.edu
J. Richards
J. M. Ehrenfeld
Department of Anesthesiology, Vanderbilt University,
1211 21st Avenue, S, 526 MAB, Nashville, TN 37212, USA
e-mail: justin.richards@vanderbilt.edu
J. M. Ehrenfeld
e-mail: jesse.ehrenfeld@vanderbilt.edu

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Introduction
Subarachnoid hemorrhage (SAH) accounts for only about
5 % of all strokes but remains a devastating disease with
mortality approaching 50 % and with less than 1 in 2 survivors reaching functional independence [1]. The

Neurocrit Care (2015) 22:184191

neurocritical care course of these patients is frequently

complicated by non-neurologic complications including
cardiorespiratory complications including the development
of acute kidney injury or AKI [2]. The intensive care course
of this patient population deviates from other ICU encounters (e.g. patients with septic shock or heart failure) due to
exposure to specific interventions and management strategies. These include potential repeated exposure to IV
contrast media, hyperosmolar agents, and euvolemic fluid
management strategies as well as development of hyponatremia, and high urine output states. Prior studies of renal
dysfunction following neurologic injury have been challenging due to the lack of a consistent, validated and
reproducible definition of acute renal failure. This has largely been overcome with the changes in the definition and
criteria for diagnosis of acute renal failure. Currently, acute
kidney injury has replaced the term acute renal failure and
has been validated in various patient populations by the
RIFLE and AKIN criteria [3]. However, little is known
about the specific risk factors for AKI in the SAH patient
population and its subsequent impact on outcomes [4].
Specific Aim
In this retrospective analysis, we seek to study the incidence, risk factors, and outcomes following development
of new onset acute kidney injury (based on the new validated definition) following SAH (SAHAKI) population
admitted to a large academic neuro intensive care unit.

Materials and Methods

Our retrospective study was approved by the Vanderbilt
University Institutional Review Board. We set out to analyze all patients admitted to the Vanderbilt neuroscience
intensive care unit with the diagnosis of SAH (aneurysmal
and non-aneurysmal) between 2006 and 2012. Traumatic
brain injury patients were not in the dataset since at our
institution, their primary location of admission is a different ICU. We excluded patients who did not survive the first
24 h of admission, and patients on renal replacement
therapy (RRT). We also excluded patients whose primary
source of intracranial blood was not a SAH (e.g. a large
intraparenchymal bleed with some subarachnoid blood was
excluded).
Data Collection and Definitions
Preoperative data points included age, sex, height, weight,
BMI, current smoking status, diabetes mellitus, hypertension, preoperative kidney function (defined as the latest
available serum creatinine prior to admission), admission

185

neurologic exam, admission Glasgow coma score, Hunt and

Hess class of SAH, and location of bleed and aneurysm (if
applicable). Intensive care variables included duration of
mechanical ventilation, intracranial hypertension, hyperosmolar therapy (mannitol and hypertonic saline), daily fluid
balances, and transfusion support (including use of packed
red blood cells, fresh frozen plasma, cryoprecipitate, and
recombinant Factor 7). Laboratory values assessed included
daily maximum and minimum serum sodium, minimum and
maximum serum osmolality. All variables were followed for
14 days post ICU admission. The primary outcome was
development of AKI based on the acute kidney injury network (AKIN) serum creatinine (sCr) criteria. The secondary
outcomes were intensive care length of stay (LOS) and 28day mortality. Data were obtained from the Vanderbilt
Perioperative Data Warehouse, an IRB-approved data registry containing case and outcomes information on all
surgical and ICU patients cared for at our institution.
The AKIN criteria has been utilized and validated in
prospective studies in patients with AKI after cardiac surgery, septic shock, ARDS, and mixed ICU populations [3].
Stage 1 in the AKIN classification includes patients with an
increase in sCr of at least 0.3 mg/dl over baseline, since there
is accumulating evidence that even minor increments in
serum creatinine are associated with adverse outcomes. Stage
2 is defined as an increase of 23 fold over the baseline sCr.
Any patient treated with RRT, irrespective of urine output or
sCr, or with a C3 fold rise in sCr is categorized as stage 3 in
the AKIN system. The AKIN classification uses a 48-hour
time window for assessment of renal function based on the
evidence that adverse outcomes were reported when the
creatinine elevation occurred within 2448 h of hospitalization [5]. In the AKIN definitions, the thresholds for urine flow
for the definition of AKI have been derived empirically and
are less well substantiated than the thresholds for increase in
SCr. Urine output has traditionally been a bellwether of renal
dysfunction in the general ICU patient population. The SAH
patient population is frequently complicated by high output
renal states such as cerebral salt wasting, and the AKIN urine
output criteria have not been validated in this patient population. We chose to use the creatinine-based definition of
AKI, with the most recent serum creatinine including upto
day of admission being considered the baseline value. Preoperative renal insufficiency was defined as a baseline serum
Cr C1.2 mg/dl. The decision to initiate RRT was at the
discretion of the attending consultant nephrologist. Although
hypertonic saline is used in varying strengths from 3 %
solution (513 mmol/L), 7.5 % solution (1283 mmol/L), or in
a 23.4 % solution (4008 mmol/L), in our study hypertonic
saline was limited to 3 % NaCl.
We followed the patients for development of SAHAKI
for a period of 14 days. We focused on this time frame
since this is considered the highest risk period for clinically

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significant vasospasm and subsequent exposure to multiple

interventions.
Statistical Analysis
Patient demographics and clinical data were summarized
using the 25th percentile, median, and 75th percentile for
continuous variables, and with percentages for categorical
variables. Unadjusted comparisons between those who did
and did not develop AKI on demographic and clinical data
were conducted using the Wilcoxon rank sum test for continuous variables and the Pearson Chi square test for
categorical variables. The AKI incidence and mortality rate
were estimated and reported with 95 % confidence intervals
using a nonparametric bootstrap method. Unadjusted AKI
free survival was depicted using a KaplanMeier curve.
Serum creatinine was measured daily from ICU admission (day 1) to discharge or day 14 whichever was the
earlier. The primary outcome was indicated when serum
creatinine increased by more than 0.3 mg/dl within a 48hour period. Patients were removed from the at-risk pool
once AKI had been observed. Patients who did not develop
AKI during their ICU stay were censored at the time of
ICU discharge or at 14 days, whichever came earlier. A
Cox proportional hazards model with time varying covariates was used to identify risk factors for developing AKI
during the ICU stay. The fixed risk factors included patient
age at hospital admission, sex, diabetes mellitus, preexisting renal disease, and Glasgow coma score. The time
varying risk factors included the cumulative count of radiocontrast exposure in days, the cumulative count of days
on mechanical ventilation, and the running maximum of
daily maximum serum sodium concentration.
All analyses were implemented using R 3.0.2 (R
Foundation for Statistical Computing, Vienna, Austria). A
significance level of 0.05 was used for statistical inference.

Results
Our study included 736 consecutive adult SAH patients with
an overall AKISAH incidence of 9.0 % (64 out of 736).
Patients who developed AKI had an increased length of ICU
stay (15.6 9.4 vs. 12.5 8.7 days, p = 0.002). The
overall mortality in the AKI cohort was 0.25 (95 % CI 0.16,
0.36) and 0.12 (95 % CI 0.10, 0.15) in non-AKI patients.
The unadjusted odds of death were more than two fold
greater among patients who developed AKI during their
clinical ICU course (odds ratio 2.33 95 % CI 1.27, 4.3).
Among the 64 patients in the AKI cohort, 58 (90.6 %)
patients had a change in serum Cr <199 % of baseline
hence classifying them as AKI-Class I. Two patients had a
sCr increase from 200 to 299 % of baseline and were

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Neurocrit Care (2015) 22:184191

classified as Class II AKI. There were only 2 patients who

needed RRT and or had an increase of sCr >300 % putting
them in the AKI-Class III category.
Of the 736 patients in our final cohort, the majority
patients were female (59 %). The median age at time of
hospital admission was 55 15 Y. Among those who
developed AKI, 19 and 14 % of the patients had diabetes
mellitus and preexisting renal disease respectively, compared to 12 and 6 % of patients who did not develop AKI.
There was a difference in the baseline count of patients
with diabetes mellitus (p = 0.016) and exposure to packed
red cell transfusion (p = 0.054) in the AKI versus no-AKI
group (Table 1).
However, there was no statistically significant difference
between cohorts with regard to admission Glasgow coma
score [11.3 4.9 in the AKI cohort and 11.7 4.6 in nonAKI cohort, (p = 0.69)]. Mechanical ventilation was initiated on admission in 35 % (22/63) of patients in the AKI
cohort compared to 29 % (194/669) in the No AKI cohort.
However, there was no statistically significant difference
between the cohorts regarding endotracheal intubation and
mechanical ventilation on admission (p = 0.32). There was
no significant unadjusted difference between cohorts with
respect to exposure to hypertonic saline, mannitol, IV
contrast, or baseline levels of serum sodium on admission.
A Cox proportional hazards regression with multiple time
varying covariates was implemented to evaluate the effect of
specific risk factors and development of AKISAH. We utilized
previously published independent risk factors as predictors of
AKISAH [6]. These independent risk factors included age,
sex, preexisting kidney disease, and DM. The SAH centric
risk factors for AKI that we explored included packed red
blood cell transfusions, exposure to contrast, and location of
bleed, etiology of SAH (aneurysmal vs. non-aneurysmal),
Glasgow coma score on presentation, mechanical ventilation,
highest serum sodium every 24 h, 24 h fluid balances, and
BMI. The results are shown in Table 2.
There was insufficient evidence associating the development of AKI with age, sex, diabetes mellitus, preexisting
renal disease, GCS, and cumulative count of radiocontrast
exposure or cumulative count of days on mechanical
ventilation.
The KaplanMeier (KM) curve for the unadjusted time
to development of AKISAH is illustrated in Fig. 1. The first
peak of AKI developed around day 3 followed by a second
smaller peak by day 7. An estimated six percent of patients
developed early AKISAH by day 3, rising to 12 % at 14 days.
Intravenous contrast media is a known risk factor for
development of acute kidney injury. We explored the
temporal exposure patterns of patients to IV contrast over a
period of 14 days. The exposure to IV contrast exposure is
shown in Fig. 2 (contrast exposure). The highest exposure
was on day 1 (39.3 % of all patients) as anticipated, due to

Neurocrit Care (2015) 22:184191

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Table 1 Patient demographics and baseline characteristics

Age

AKI
(N = 64)

No AKI
(N = 672)

Combined
(N = 736)

49, 56, 73

45, 55, 65

45, 55, 65

0.17

(55 15)

(59 16)

(55 15)

Female

53 % (34/64)

60 % (402/672)

59 % (436/736)

0.3

BMI

23.0, 26.6, 31.3

23.1, 25.9, 30.4

23.1, 26.0, 30.4

0.94

(28.2 8.3)

(28.1 11.1)

(28.1 10.9)

Diabetes mellitus-type II (%)

19 % (12/64)

12 % (84/672)

13 % (96/736)

0.16

Preexisting renal disease (%)

Glasgow coma score

14 % (8/64)
7.0, 15.0, 15.0

6 % (40/672)
8.0, 15.0, 15.0

7 % (51/736)
7.0, 15.0, 15.0

0.07
0.69

(11.3 4.9)

(11.7 4.6)

(11.6 4.7)

Contrast exposure(%)

44 % (28/64)

39 % (261/672)

39 % (289/736)

0.44

Mannitol (%)

6 % (4/64)

3 % (20/672)

3 % (26/736)

0.23

Sodium

0, 137, 140

0, 137, 140

0, 137, 140

0.39

(100 64)

(93 65)

(94 65)

Osmolality
RBC transfusion

296, 308, 320

298, 304, 314

298, 305, 317

(303 25)

(308 18)

(308 19)

4.5 % (3/64)

1 % (7/672)

1.3 % (10/736)

0.94
0.054

Summary statistics are shown as the 25th, 50th, 75th percentile (mean SD) for continuous variables, percentage for categorical variables. p
values were calculated using the Wilcoxon rank sum test for continuous variables and the Pearson Chi-square test for categorical variables
Table 2 Effect estimate (95 % CI) calculated from the time varying
Cox proportional hazard model
Variable

HR (95 % CI)

Age

1.02 (0.99, 1.04) 0.16

Female

0.74 (0.42, 1.30) 0.29

Diabetes mellitus

1.55 (0.82, 2.94) 0.18

Preexisting renal disease

1.45 (0.55, 3.81) 0.45

Glasgow coma score

1.02 (0.96, 1.09) 0.47

Cumulative maximum sodium

1.06 (1.01, 1.10) 0.008

Cumulative count of radiocontrast exposure 1.09 (0.78, 1.53) 0.62

Cumulative count of days on mechanical
1.04 (0.96, 1.12) 0.36
ventilation

concentration (mEq/L). The distribution of daily maximum

sodium is shown in Fig. 3. Hypernatremia (secondary to
the use of hypertonic saline) and even small increments of
daily serum sodium was a significant risk factor for AKISAH after adjusting for other risk factors. The strongest risk
factor associated with development of AKI in the SAH
patient population was the daily maximum serum sodium.
For each 1 mEq/L increase in the running maximum of
daily maximum serum sodium, the hazard of developing
AKI was increased by 5.5 % (95 % CI 1.4, 9.7, p value =
0.008).

Discussion
the nature of the diagnostic workup of a SAH. This
exposure was reduced significantly by day 3 (about 3.5 %
of patients being exposed) and continued to be low at about
5 % until day 8 and 9. There was a second peak of contrast
exposure on day 8 and 9 (10.4 and 17 % respectively).
However, based on our Cox proportional hazards regression model, in spite of significant exposure, there was
insufficient evidence that the running count of IV contrast
exposure events was a significant risk factor for AKISAH in
our patient population. After adjusting for other covariates
including sodium exposure, HR for AKI was 1.09 (0.78,
1.53); p = 0.62.
Sodium exposure was used as a surrogate for hypertonic
saline therapy in our analysis and was captured as the
running maximum of daily maximum serum sodium

Significant strides have been made in the neurologic

management of SAH in the past decade. The focus now
rests on minimizing the non-neurologic complications
associated with this disease that still has a high morbidity
and mortality [7]. Identification of patient and procedural
risk factors may therefore allow for improvements in longterm outcome by affecting changes in perioperative management and disease prevention.
In our analysis, the overall incidence of AKI was 9 %,
which is lower compared to reported AKI rates in post
cardiac surgical and general post surgical intensive care
units, where rates as high as 47 % have been reported [8].
Hypernatremia secondary to the use of hypertonic saline
was the strongest risk factor for developing AKISAH in our

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Neurocrit Care (2015) 22:184191

Fig. 1 KaplanMeier curve

showing the timeline to develop
AKI in the ICU in the SAH
patient population

Fig. 2 Temporal trend of IV contrast exposure in all patients

showing the proportion of patients (%) exposed to I.V. contrast
between ICU day 1 and ICU day 14

patient population. Interestingly, the traditional risk factors

for AKI in mixed ICU populations such as diabetes mellitus, preexisting kidney disease, advanced age were not
significant risk factors for developing AKI in our SAH
population. Contrast-induced nephropathy was not a significant event in our patient population in spite of
increasing frequency of contrast exposure each year of the
study in the SAH patient population. Patients who developed new onset AKI had an increased length of stay and
were at an increased risk of in-hospital mortality.
Raised intracranial pressure (ICP) is an independent
predictor of poor neurologic outcome following SAH.
Intracranial hypertension and cerebral edema are cardinal
manifestations of severe brain injury resulting from diverse

123

insults ranging from traumatic brain injury to SAH. Early

and aggressive management of intracranial hypertension is
a key to a good outcome.
Hyperosmolar therapy with mannitol and hypertonic
saline has been the cornerstone in the management of
intracranial hypertension [9]. Recent studies including a
metaanalysis showed HS to be more effective with controlling ICP compared to mannitol [10]. The intensivist
preferences of using mannitol versus hypertonic saline are
evenly divided based on a recent national survey [11]. In
the same survey, interestingly the major reason for the
preference for using hypertonic saline was the perceived
decreased risk of renal dysfunction compared to mannitol [11]. As our experience with the use of hypertonic
saline in various concentrations grows, we will gather a
better renal risk profile of hypertonic saline. Dominguez
et al. reported the increased risk of renal dysfunction in
pediatric patients who were maintained in a hyperosmolar
state at 160 mEq/L in severe traumatic brain injury [12]. It
is thought that hypernatremia can lead to renal dysfunction
through the mechanism of intravascular dehydration and
vasoconstriction either directly or through a tubuloglomerular feedback mechanism [13]. Animal studies have
shown a reduction of renal blood flow, glomerular filtration
rate, and an inhibition of renin secretion when the sodium
level in the renal artery is increased rapidly [14]. These
findings can be explained by the fact that the kidney, in
contrast to other organs, responds with vasoconstriction to
a hypernatremic state. HTS is not without potential major
adverse effects. While relatively rare, serious electrolyte

Neurocrit Care (2015) 22:184191

Fig. 3 Sodium max on ICU day 1 through day 14. The panel on the
top shows sodium max data for patients who developed AKI, and the
panel on the bottom shows the cohort with no AKI

disturbances may be induced central pontine myelinolysis

in malnourished patients with an acute hypernatremic state
following rapid serum sodium correction [15, 16]. Hyperchloremic acidosis and acute hemolysis are further
consequences of HTS administration. Hyperosmolar therapy is also known to induce rapid intravascular volume
expansion and subsequent cardiac overload with pulmonary edema. Further worsening of cerebral swelling and
increased ICP maybe indicative of a disrupted blood brain
barrier and a reverse osmosis phenomenon (1). In
addition, renal complications due to HTS therapy are an
real concern [15, 17].
The therapeutic management of SAH has undergone
significant changes in the past decade for SAH with the
advent of neurovascular interventions such as stenting and
endovascular coiling of aneurysms [18]. These procedures
frequently require contrast angiography to define the
anatomy, and during the therapeutic intervention as well.
Thus, with a change in the management paradigm for SAH,
patients today have a higher potential for multiple exposures to IV contrast media secondary to both diagnostic and

189

therapeutic interventions during their ICU course [19]. This

increases the risk of contrast-induced nephropathy in this
patient population. In the general patient population, hypovolemia, volume of contrast used, preexisting kidney
disease, diabetes mellitus, advanced age, and decreased left
ventricular function are established risk factors for contrast-induced nephropathy. Rate of contrast-induced
nephropathy has been reported to be as high as 2025 % in
high-risk patients (e.g. cardiac ICU patient population)
[20]. Interestingly, although there has been conflicting data
on the rates of CIN in the SAH population, the overall
incidence is lower than the general mixed ICU patient
population [21, 22]. This reflects the finding in our study as
well that exposure to IV contrast was not associated with
an increased risk of AKI SAH in our patient population over
a time course of 14 days. The precise reasons for this are
unclear at this time. We speculate that the aggressive
avoidance of hypovolemia, higher blood pressure goals,
and modified augmented cardiac index management of
cerebral vasospasm may have contributed to maintaining
effective renal perfusion and the overall increased vigilance to the risks of contrast exposures maybe a
contributing factor as well.
SAH patients pose a relatively unique set of challenges
to the intensivists compared to other non-neurologic ICU
patients. The liberal fluid management strategies (i.e. post
aneurysm intervention), sedation management, hemodynamic management (e.g. augmented cardiac index therapy)
often seem counterintuitive to other traditional ICU
patients with diseases such as ARDS and septic shock.
The overall incidence of AKI following SAH is lower
compared to the incidence following other high mortality
diagnoses such as septic shock or ARDS [23]. The precise
reasons are unclear at this time. The predominant pathophysiologic model of AKI in general ICU patients is the
ischemiareperfusion model frequently triggered by perturbations in hemodynamics leading to the development
and worsening of AKI in septic shock and ARDS [24, 25].
This clinical scenario tends to be less frequent in the SAH
patient population especially with the institution of augmented cardiac index therapy or the comparable version of
triple-H therapy in these patients. In fact, the MAP and
cardiac output may be at a higher than baseline level in the
post intervention period and during the active management
of cerebral vasospasm [26, 27]. The increasing use of
statins in patients with patients with SAH for their pleiotropic immune modulating effects (non-cholesterol
lowering effects) may further confound the picture.
Investigations have been exploring the role of statins in the
perioperative period to prevent or decrease the severity of
AKI and need for RRT [28]. Statins have been tried as a
prophylactic agent for CIN especially in the patients
undergoing coronary angiography with limited success in

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smaller studies [29, 30]. The results of numerous trials

have been conflicting and there is insufficient data at this
time to support the routine use of statins in all SAH patients
for the prevention of AKI [31, 32].
The current definitions and risk stratification of acute
kidney injury has helped better define and study the
problem of kidney dysfunction across various pathophysiologic spectra include SAH. The diagnosis of AKI using
the AKIN (Acute Kidney Injury Network) or RIFLE (Risk,
Injury, Failure, Loss, End-stage kidney disease) criteria is
currently limited as SCr and UO can only indirectly reflect
that kidney damage has occurred. There are however
continuing limitations with the current AKIN system as
well. Serum creatinine remains the most frequently used
parameter in the diagnosis of AKI. sCr is an insensitive and
unreliable biomarker during short-term changes in kidney
function because it lags behind the decline and recovery in
glomerular filtration rate by days. Moreover, sCr is affected
by age, race, muscle mass, volume of distribution, medications, and protein intake; it does not discriminate the
nature of renal insult (e.g., ischemic vs. prerenal insult). A
change in serum creatinine does not indicate the site of
kidney injury (i.e. glomerular versus tubular etc.) but rather
provides an overall index of function [33]. Therefore, there
is a need for more sensitive and specific biomarkers that
can diagnose AKI earlier, possibly indicate the cause, and
rapidly measure the response to therapy. The use of the
next generation of biomarkers for acute kidney injury such
as NGAL (neutrophil gelatinase associate lipocalin), Kidney injury molecule-1 (KIM-1) are becoming more widely
available. They may play a role in the future to further
determine the patients at risk or allow early detection of
AKI and in turn may provide a window of opportunity for
early therapeutic interventions. Robust data on the use of
biomarkers in AKI following SAH are anticipated in the
near future.
The strength of our analysis is that the data spans multiple years and multiple providers were involved with the
care of patients. The large cohort of consecutive patients
with SAH and the robustness of the data collected add
strength to our study. Certain limitations of this current
study deserve mention. This is a single center retrospective
study and the known inherent limitations of this kind of
analysis apply to this study as well. The variability of
clinical practice including fluid management, blood pressure management strategies may have had an impact on the
final outcomes. We also did not have any biomarker specific data for AKI in this patient population. Additional
studies are warranted to study the pathophysiologic processes and interventions to prevent the development of
AKI in his high mortality patient population. We anticipate
future studies to shed more light on this important nonneurologic complication following SAH.

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Neurocrit Care (2015) 22:184191

Conclusion
Hypernatremia is independently associated with an
increased risk of development of AKI in the SAH patient
population. Patients who developed AKI had an increased
length of stay and a significantly increased 28-day mortality. Understanding the risk posed by hypernatremia in
the pathogenesis of AKI after SAH may help us develop
management strategies to minimize harm to the kidneys in
this high mortality disease.
Conflict of interest
conflict of interest.
Funding

All the author declared that they have no

Departmental funds only.

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