Journal of Critical Care 55 (2020) 157–162

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Journal of Critical Care

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Fluid resuscitation in patients with end-stage renal disease on

hemodialysis presenting with severe sepsis or septic shock: A case
control study
Kartikeya Rajdev, MBBS ⁎, Lazer Leifer, MD, Gurkirat Sandhu, MD, Benjamin Mann, MD, Sami Pervaiz, MD,
Saad Habib, MBBS, Abdul Hasan Siddiqui, MD, Bino Joseph, MD, Seleshi Demissie, DrPH, Suzanne El-Sayegh, MD
Northwell Health-Staten Island University Hospital, Department of Internal Medicine, 475 Seaview Avenue, Staten Island, NY 10305, United States of America

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

Due to the potential risk of volume overload, physicians are hesitant to aggressively fluid-resuscitate septic pa-
Keywords: tients with end-stage renal disease (ESRD) on hemodialysis (HD). Primary objective: To calculate the percentage
End-stage renal disease of ESRD patients on HD (Case) who received ≥30 mL/Kg fluid resuscitation within the first 6 h compared to non-
Hemodialysis ESRD patients (Control) that presented with severe sepsis (SeS) or septic shock (SS). Secondary objectives: Effect
Severe sepsis of fluid resuscitation on intubation rate, need for urgent dialysis, hospital length of stay (LOS), intensive care unit
Septic shock
(ICU) admission and LOS, need for vasopressors, and hospital mortality. Medical records of 715 patients with sep-
Fluid resuscitation
Surviving sepsis campaign
sis, SeS, SS, and ESRD were reviewed. We identified 104 Case and 111 Control patients. In the Case group, 23% of
Early goal-directed therapy patients received ≥30 mL/Kg fluids compared to 60% in the Control group (p b 0.001). There was no significant
difference in in-hospital mortality, need for urgent dialysis, intubation rates, ICU LOS, or hospital LOS between
the two groups. Subgroup analysis between ESRD patients who received ≥30 mL/Kg (N = 80) vs those who re-
ceived b30 mL/Kg (N = 24) showed no significant difference in any of the secondary outcomes. Compliance with
30 mL/Kg fluids was low for all patients but significantly lower for ESRD patients. Aggressive fluid resuscitation
appears to be safe in ESRD patients.
© 2019 Elsevier Inc. All rights reserved.

1. Background
Sepsis and bacterial infections are common in patients with end-
stage renal disease (ESRD). Infection is the second most common
cause of mortality in ESRD patients after cardiovascular disease [1-3].
Every year in the United States (US) 750,000 patients are diagnosed
with severe sepsis (SeS), with an average annual increase of 13.0%. Sep-
sis is currently the 10th leading cause of mortality in the US [1-3]. Septic
patients are at a risk for fluid imbalance due to a widespread systemic
inflammation and increased capillary permeability [4]. The goal in the
management of septic shock (SS) is to avoid hypovolemia and its related
complications, such as hypotension, kidney injury, and multi-organ fail-
ure [5]. The mortality in septic patients prior to 2001 was considerably
high, ranging between 30% and 60% [6]. A general notion of urgency in
⁎ Corresponding author at: 361 N 46TH St Apt 3208, Omaha, NE 68132, United States of
America.
E-mail address: kartikeyarajdev@gmail.com, kartikeya.rajdev@unmc.edu (K. Rajdev),
lazerleifer@gmail.com (L. Leifer), gsandhu@northwell.edu (G. Sandhu),
ben.mann91@gmail.com (B. Mann), spervaiz3@northwell.edu (S. Pervaiz),
ssaadhabib@gmail.com (S. Habib), drsiddiqui07@gmail.com (A.H. Siddiqui),
bino.md@gmail.com (B. Joseph), sdemissie@northwell.edu (S. Demissie),
selsayegh@northwell.edu (S. El-Sayegh).
the management of patients with SeS or SS was lacking. The Surviving
Sepsis Campaign (SSC) guidelines recommend an initial fluid resuscita-
tion of at least 30 mL/Kg of body weight in the first 3 h of diagnosis of
SeS or SS [7]. The original guidelines of the SSC were based on the land-
mark randomized controlled trial (RCT) published in 2001 by Rivers
et al. Rivers et al. reported a 16% reduction in mortality (46.5% to
30.5%) with the use of a protocolized based approach to treat patients
with SeS or SS which was termed as Early Goal-Directed Therapy
(EGDT) [8]. The study also emphasized on early identification of sepsis
and time-dependent management of patients with SeS or SS and was
a breakthrough in the field of sepsis. Physicians became more aggressive
in managing sepsis since the publication of this trial. Although EGDT
was incorporated into the SSC guidelines, there were concerns on the
validity of its individual components and the complexity of the protocol.
Recently, 3 large multi-center RCTs, namely ProCESS, ProMISe, and
ARISE, showed no improvement in mortality in patients who received
EGDT compared to the usual care or less invasive hemodynamic resus-
citation protocols [5,9-12]. The usual care in these 3 trials required
early identification of SeS and SS with standardized screening protocols,
including measurement of lactic acid, as well as early administration of
fluids and antibiotics. In response to the new evidence from these three
trials, the current SSC guidelines do not recommend use of a central

https://doi.org/10.1016/j.jcrc.2019.10.008
0883-9441/© 2019 Elsevier Inc. All rights reserved.
158 K. Rajdev et al. / Journal of Critical Care 55 (2020) 157–162
venous catheter to measure central venous pressure or central venous
oxygen saturation in all patients with SeS or SS who have received
timely antibiotics and fluid resuscitation [9]. The guidelines recommend
administration of at least 30 mL/Kg of crystalloid fluid for SeS or SS
within 3 h of presentation [7,9]. This initial fluid resuscitation of
30 mL/Kg is a strong recommendation (with a low quality of evidence)
and is meant to enable clinicians to initiate resuscitation in SeS or SS
while waiting for further information on their hemodynamic status
and clinical parameters. The use of 30 mL/Kg fluid resuscitation has
been described as usual practice in recent interventional and observa-
tional studies; although, there is limited literature that provides con-
trolled evidence to support 30 mL/Kg of fluid resuscitation [9,13,14].
The average amount of fluid patients received prior to randomization
in ProCESS and ARISE trial was close to 30 mL/Kg and around 2 L in
the ProMISe trial [9-12]. Many patients require more fluids after the ini-
tial fluid resuscitation. The SSC guidelines recommend evaluation of he-
modynamic status using clinical and physiological variables, as well as
other invasive and non-invasive monitoring. This includes maneuvers
such as a passive leg raise, fluid challenge, and bedside echocardiogra-
phy, among others [6,9,15].
In the hospital, physicians often encounter hypotensive ESRD pa-
tients presenting from a dialysis center. Hypovolemia is usually the
first impression of most clinicians. The diagnosis of sepsis in these pa-
tients requires a high index of suspicion and is often not straightforward
[16]. There is a plethora of evidence that early identification of sepsis
and early administration of fluid resuscitation and antibiotics in patients
with hypotension or sepsis-induced tissue hypoperfusion decreases in-
hospital mortality. It also improves morbidity by decreasing the occur-
rence of severe organ dysfunction, as well as both hospital and intensive
care unit (ICU) length of stay (LOS) [7-9,17]. However, most of these
studies have looked at a general patient population. There is a paucity
of information about the use of aggressive fluid resuscitation in ESRD
patients on hemodialysis (HD). ESRD patients on HD often have a com-
plex presentation during sepsis. Often, they appear volume overloaded
on physical examination. However, they may actually be volume de-
pleted intravascularly [16]. Due to risk of potential complications such
as hypertension, pulmonary edema, respiratory failure, intubation, ur-
gent dialysis, and increased cardiac demand, health care providers are
hesitant to aggressively fluid-resuscitate septic patients who are at in-
creased risk of fluid overload, such as patients with ESRD on HD.
A study by Akhter et al. found no difference in the rate of intubation,
hospital LOS, or mortality among patients with ESRD or congestive heart
failure (CHF) who presented with SeS or SS and received an initial fluid
resuscitation of ≥30 mL/Kg (N = 27) vs b30 mL/Kg (N = 169). They also
found that ESRD and CHF patients were significantly less likely to re-
ceive 30 mL/Kg of fluids in the ED compared to non-ESRD and non-
CHF patients [18]. Omar et al. found that patients on dialysis (N = 28)
received less fluids compared to patients not on dialysis (N = 30).
They concluded that conservative fluid resuscitation of ESRD patients
in SeS or SS might be associated with improved outcomes [19]. Ozuzun
et al. showed that there were no direct complications of fluid overload
in ESRD patients who received ≥30 mL/Kg crystalloids (N = 13) com-
pared to ESRD patients who received b30 mL/Kg (N = 21) for SeS or
SS [20]. Lee et al. conducted a study on 329 patients with ESRD on dial-
ysis and SeS or SS to evaluate the relationship between fluid resuscita-
tion bundle compliance and in-hospital mortality. However, they
defined fluid resuscitation bundle compliance as receiving ≥20 mL/Kg
within 1 h before and 6 h after SeS or SS recognition. They found no dif-
ference in mortality between fluid resuscitation bundle complaint (N =
214) vs non-compliant patients (N = 115) [21].
The aim of our project was to retrospectively study a series of pa-
tients with ESRD on HD diagnosed with SeS or SS and compare with an-
other subset of patients without ESRD diagnosed with SeS or SS. The
study was intended to determine what percentage of patients with
ESRD on HD received an initial fluid resuscitation of ≥30 mL/Kg com-
pared to non-ESRD patients, and whether aggressive (≥30 mL/Kg) vs
restrictive (b30 mL/Kg) fluid resuscitation in patients presenting with
SeS or SS led to an increased rate of intubation, urgent dialysis, affected
hospital length of stay (LOS), intensive care unit (ICU) LOS, need for va-
sopressors, in-hospital mortality, and other secondary outcomes. We
intended to shed light on this special subset of population. This informa-
tion could be of use to emergency physicians, hospitalists, intensivists
and nephrologists.
2. Objectives
2.1. Primary objective
To assess the percentage of ESRD patients on HD (Case group) who
received initial fluid resuscitation of ≥30 mL/Kg in comparison to pa-
tients without ESRD (Control group) presenting to the hospital with
SeS or SS.
2.2. Secondary objectives
1. To evaluate and compare the following endpoints among the Case
and Control group:
a) Incidence of mechanical ventilation for respiratory distress.
b) Duration of mechanical ventilation.
c) Time to order antibiotics since presentation.
d) Hospital LOS and In-hospital mortality
e) ICU admission and ICU LOS
f) Incidence of urgent dialysis for volume overload
g) Need for vasopressors and number of vasopressors required dur-
ing hospitalization
h) Source of infection
2. To perform sub-group analysis of the Case group (ESRD) and com-
pare the same secondary outcomes in the sub-set of ESRD patients
who received ≥30 mL/Kg fluid resuscitation vs those who received
b30 mL/Kg fluid resuscitation for SeS or SS.
3. Methods
The study was a case-control chart review study. Medical records of
adult patients with International Classification of Diseases (ICD) code
for a discharge diagnosis of sepsis, SeS, SS, ESRD and HD from the year
2015 to 2018 were retrieved from the department of health records of
our institution. Patients were included if they met the criteria for SeS
or SS based on the definitions by SSC. Patients younger than 18 years
old, pregnant patients, and patients with incomplete or illegible docu-
mentation were excluded. 715 patient records were screened for eligi-
bility, out of which 215 met the criteria for severe sepsis or septic
shock. Patients were divided into two groups. The Case group belonged
to the patients with ESRD on HD admitted with a diagnosis of SeS or SS.
The Control group included patients without ESRD (not on dialysis) ad-
mitted with a diagnosis of SeS or SS. Only the authors of the study had
access to the collected data that was stored in a secure environment
on REDCap.
The diagnosis of SeS and SS was based on the 1991 and 2001
consensus documents [22]. Severe Sepsis was defined as two systemic
inflammatory response syndrome (SIRS) criteria (temperature N 38 °C
(100.4 °F) or b 36 °C (96.8 °F), respiratory rate N 20 breaths/min, heart
rate N 90 beats/min or white blood cell count (WBC) N12 × 109/L or
b 4 × 109/L and sepsis-induced organ dysfunction or tissue hypoperfu-
sion (systolic blood pressure ≤ 90 mmHg or MAP ≤70 mmHg or a fall
of N40 mmHg from baseline or serum lactate ≥4 mmol/L regardless of
the blood pressure). Septic shock is defined as sepsis-induced hypoten-
sion persisting despite a 30 mL/Kg fluid bolus.
A REDCap data entry sheet was designed to collect the following
information.
 K. Rajdev et al. / Journal of Critical Care 55 (2020) 157–162 159

• Patient's demographics including age, gender, and ethnicity.

• Presence or absence of ESRD on HD (allocation to Case vs Control
group).
• Co-morbidities including a history of hypertension, diabetes, coronary
artery disease, CHF, cerebrovascular accidents, malignancy, immuno-
suppression, Human Immunodeficiency Virus (HIV) status, dementia
and the presence of other comorbidities were obtained from patient's
medical record and the Charlson Comorbidity Index (CCI) for all pa-
tients was calculated.
• Patients' clinical presentation and findings at initial presentation to
the ED including temperature, blood pressure, mean arterial pressure,
respiratory rate, heart rate, lactic acid, WBC count, creatinine and esti-
mated Glomerular Filtration Rate (eGFR) was collected.
• Time to ordering antibiotics from the time of presentation. The time of
presentation was defined as the time of triage in the ED.
• Amount of fluid resuscitation (in mL) within the first 6 h of presenta-
tion
• Incidence of intubation due to respiratory failure within the first 24 h
of presentation.
• Duration of mechanical ventilation in days.
• Need for vasopressors.
Fig. 1. Depicting the number of patients in the Case (ESRD) and Control (non-ESRD) group.
• Number of vasopressors required during hospitalization.
• Rate of ICU admission.
• ICU LOS in days. presentation in comparison to 60.36% (N = 67/111) of patients in the
• Incidence of urgent dialysis for volume overload. Control group presenting to the ED for SeS or SS (Fig. 2) (p b 0.001).
• Source of infection e.g. pneumonia, urinary track infection, intra- Our study evaluated many secondary outcomes which are depicted in
abdominal infection, skin/soft tissue/intravenous line infection, dialy- Table 2. The mean amount of fluids received in the Case group was
sis catheter or fistula site infection. 21.38 mL/Kg compared to 36.28 mL/Kg in the Control group which
• Hospital LOS in days. was statistically significant (p b 0.001). The mean total amount of fluids
• In-hospital mortality. (mL) in the first 6 h of presentation to ED was 1643.30 mL in the Case
group and 2669.80 mL in the Control group (p b 0.001). The median
3.1. Statistical analysis time to ordering antibiotics since presentation to the ED was not signif-
icantly different between the two groups. There was no significant dif-
Summary statistics were reported as mean (standard deviation) for ference in the rate of intubation for respiratory distress within 24 h of
normally distributed continuous variables and as median (interquartile presentation between the Case and the Control group (p N 0.05). 38 pa-
range) for not normally distributed continuous variables. Categorical tients had DNI (Do Not Intubate) as their code status and were therefore
variables were summarized as frequency and percentages. Differences excluded from the intubation rate calculation. 1.97% of patients in the
in continuous variables between case (ESRD) and control (non-ESRD)
group patients were evaluated using independent-sample t-Test or
nonparametric Mann-Whitney U test, as appropriate. The Chi-square Table 1
or Fisher's exact test was used to compare categorical variables between Baseline demographic and clinical characteristics of the case and control group.
groups. A multivariate logistic regression model was performed to ex- Case group Control group P-value
plore the difference between ESRD and non-ESRD patients in mortality (ESRD) (104) (non-ESRD) (111)
adjusting for confounding effects of age, fluid intake, time to antibiotics, Male 72 (69.23%) 72 (64.86%) 0.563
CHF, and CCI. All statistical tests of significance are two-sided and con- Female 32 (30.77%) 39 (35.14%)
ducted at the 0.05 level of significance. Statistical analyses were con- Age (years) 70.25 SD = 11.36 72.30 SD = 12.98 0.221
ducted using SAS (Statistical Analysis System) software Version 9.3. Ethnicity 0.243
• Caucasian 79 (75.96%) 92 (82.88%)
• African-American 13 (12.50%) 8 (7.21%)
4. Results • Asians 5 (4.80%) 2 (1.80%)
• Hispanics 3 (2.88%) 1 (0.90%)
We identified 104 patients with ESRD on HD with SeS or SS (Case • Others 4 (3.85%) 8 (7.21%)
*Charlson comorbidity index 8 (3) 6 (4) b0.001
group) and 111 patients without ESRD with SeS or SS (Control group)
*Lactic acid (mmol/L) 2.70 (3.15) 3.75 (3.9) 0.039
(Fig. 1). Both groups had similar distributions of patients in terms of Creatinine (mg/dL) 5.66 SD = 2.26 3.19 SD = 3.64 b0.001
age, sex and ethnicity. The majority of our patient population was el- GFR (mL/min) 11.31 SD = 6.13 35.93 SD = 24.69 b0.001
derly males with a mean age of 70.25 years in the Case group and SBP (mm Hg) 84.46 SD = 20.52 89.93 SD = 24.57 0.079
72.30 years in the Control group. Our sample was predominantly DBP (mm Hg) 48.96 SD = 11.23 53.03 SD = 12.68 0.014
MAP (mm Hg) 60.68 SD = 13.38 65.21 SD = 15.55 0.023
comprised of Caucasian patients, which is consistent with the popula-
Heart rate (beats/min) 98.70 SD = 21.37 110 SD = 24.32 b0.001
tion distribution and demographics of Staten Island, New York. CCI Temperature (F) 98.59 SD = 3.16 99.40 SD = 3.34 0.068
was calculated for all patients and patients with ESRD had significantly Respiratory rate (breaths/min) 20.46 SD = 4.29 21.54 SD = 4.69 0.080
higher CCI than the control group. Table 1 demonstrates the baseline *WBC (x109/L) 14.42 (11.69) 13.81 (9.5) 0.307
demographic and clinical characteristics of our patient population. Quantitative clinical characteristics are presented as mean and standard deviation (SD)
except the ones with an asterisk. Due to the skewed distribution of data, the characteristics
4.1. Primary and secondary objectives with an asterisk are presented as median with interquartile range in parenthesis. Abbrevi-
ations- ESRD- End Stage Renal Disease, GFR- Glomerular Filtration Rate, SBP-Systolic Blood
Pressure, DBP- Diastolic Blood Pressure, MAP- Mean Arterial Pressure, F- Fahrenheit, WBC-
We found that 23.08% (N = 24/104) of patients in the Case group White Blood Cell.
received ≥30 mL/Kg fluid resuscitation within the first 6 h of P values in bold are statistically significant.
160 K. Rajdev et al. / Journal of Critical Care 55 (2020) 157–162

Table 3
Multivariate logistic regression analysis for mortality.

Variable Odds ratio (Confidence P-value

interval)

Age (1 year increment) 1.029 (1.001–1.057) 0.044

Fluids in mL/Kg in first 6 h of presentation 0.981 (0.963–0.999) 0.035
Charlson comorbidity index 1.091 (0.954–1.247) 0.206
Time to order antibiotics (Hours) 1.007 (0.869–1.166) 0.930
ESRD vs non-ESRD 0.610 (0.310–1.198) 0.151
SBP (mm Hg) 0.992 (0.979–1.005) 0.235
Lactic Acid (mmol/L) 1.150 (1.042–1.269) 0.005
CHF 1.385 (0.712–2.685) 0.337

Parenthesis represent confidence intervals. Abbreviations- ESRD- End Stage Renal Disease,
SBP- Systolic Blood Pressure, CHF- Congestive Heart Failure.
P values in bold are statistically significant.

We performed a multivariate logistic regression analysis to explore

Fig. 2. Depicting the percentage of patients who received ≥ 30 mL/Kg fluid resuscitation in
the Case (ESRD) and Control (non-ESRD) group.
Case group needed urgent dialysis for volume overload compared to 0%
patients in the Control group. This difference was not significant (p =
0.228). Patients in the Control group were noted to have a significantly
higher ICU admission rate (p = 0.03) and the need for vasopressor sup-
port (p = 0.02). Most of the patients who needed vasopressor support
required up to two vasopressors. The ICU LOS, hospital LOS, and dura-
tion of mechanical ventilation were not statistically significantly differ-
ent between the two groups. Pneumonia was the most common cause
of SeS or SS in both the groups. Urinary tract infections were more com-
mon in the Control group whereas skin and soft tissue and intravenous
line infections were more common in the Case group. 39.42% of the pa-
tients in the Case group expired during the hospitalization compared to
42.34% in the Control group. This difference in in-hospital mortality was,
however, not statistically significant (p = 0.68).
the difference in mortality by adjusting for confounding effects of age,
amount of fluids (mL/Kg) received in the first 6 h of presentation, time
to administer antibiotics (hours), presence of CHF, ESRD vs non-ESRD,
and CCI (Table 3). The results showed that age was significantly associ-
ated with mortality (p = 0.044) with an odds ratio of 1.029. This sug-
gests that with every one-year increase in patient's age, the mortality
increased by around 2.9%, after adjusting for the other variables.
Patients with higher lactic acid were associated with higher mortality
(p b 0.01). Fluid administration was independently associated with
lower mortality in patients with SeS or SS (p = 0.035). Other factors
such as time to antibiotics, systolic blood pressure, CCI, and presence
of ESRD were not found to be independently associated with mortality.
4.2. Sub-group analysis of ESRD patients (Case group)
A sub-group analysis was performed to compare the secondary
outcomes between ESRD patients who received b30 mL/Kg fluid resus-
citation (Sub-group 1 - N = 80) vs those who received ≥30 mL/Kg fluid
resuscitation (Sub-group 2 - N = 24). Table 4 demonstrates a similar
distribution of patients in both the groups with respect to age, sex,
CCI, and clinical parameters upon presentation to the ED (p N 0.05).

Table 2
Comparison of secondary outcomes between the case and control group.

Case group (ESRD) (104) Control group (non-ESRD) (111) P-value

Fluids received (mL/Kg) 21.38 SD = 15.86 36.28 SD = 19.22 b0.001

Total amount of fluids (mL) in first 6 h of presentation 1643.30 SD = 1156.50 2669.80 SD = 1261.10 b0.001
*Time to order antibiotics (Hours) 1.38 (2.00) 1 (1.50) 0.168
ICU admission rate 69 (66.35%) 89 (80.18%) 0.030
*ICU LOS (Days) 5 (5) 4 (6) 0.073
Need for vasopressors 56 (53.85%) 77 (69.37%) 0.025
Number of vasopressors 0.034
• 1 45 (80.36%) 53 (68.83%)
• 2 11 (19.64%) 14 (18.18%)
• 3 0 7 (9.10%)
• 4 0 3 (3.90%)
Intubation rate within 24 h of presentation for respiratory distress 7 (8.64%) 12 (13.04%) 0.467
*Length of mechanical ventilation (Days) 5 (4) 6 (2.5) 0.540
Need for urgent dialysis for volume overload 2 (1.97%) 0 (0%) 0.228
*Hospital LOS (Days) 8 (11) 9 (11) 0.743
Source of Infection b0.001
• Pneumonia 47 (45.19%) 53 (47.75%)
• UTI 7 (6.73%) 31 (27.93%)
• Intra-abdominal 16 (15.38%) 17 (15.32%)
• Skin/Soft tissue/IV line 20 (19.23%) 4 (3.60%)
• Dialysis catheter/Fistula site infection 2 (1.92%) 0
• Others 12 (11.54%) 6 (5.41%)
In-hospital mortality 41 (39.42%) 47 (42.34%) 0.680

Quantitative data are presented as mean and standard deviation (SD) except the ones with asterisk. Due to the skewed distribution of data, the characteristics with asterisk are presented
as median with interquartile range in parenthesis. Abbreviations- ESRD- End Stage Renal Disease, ICU- Intensive Care Unit, LOS- Length of Stay, UTI- Urinary Track Infection,
IV- Intravenous.
P values in bold are statistically significant.
 K. Rajdev et al. / Journal of Critical Care 55 (2020) 157–162 161

Table 4 have a coexisting renal disease [23,24]. There is little literature available
Sub-group analysis of the case group. Baseline demographic and clinical characteristics of on this subset of patients. With this study, we have made an attempt to
the ESRD patients who received b30 mL/Kg fluids (Sub-group 1) vs those who received
≥ 30 mL/Kg fluids (Sub-group 2).
bridge this knowledge gap. We performed a retrospective chart review
of patients presenting to the ED with SeS or SS and evaluated the fluid
Sub-group 1 (80) Sub-group 2 (24) P-value resuscitation in patients with and without ESRD. We found that compli-
Male 56 (70%) 16 (66.67%) 0.802 ance with the SSC guidelines of at least 30 mL/Kg fluid resuscitation was
Age (years) 69.20 SD = 11.17 73.79 SD = 11.52 0.082 low for all patients at our institution but was much lower for patients
*Charlson Comorbidity Index 7 (2.5) 8 (3.5) 0.593
with ESRD. These findings are in line with the previously described
*Lactic acid (mmol/L) 2.75 (3) 2.55 (5) 0.793
SBP (mm Hg) 85.25 SD = 22.68 81.83 SD = 10.49 0.477 literature [19-22]. As mentioned above, this may be due to a fear of
DBP (mm Hg) 48.86 SD = 11.94 49.29 SD = 8.70 0.870 causing volume overlaod in ESRD patients.
MAP (mm Hg) 60.87 SD = 14.58 60.03 SD = 8.40 0.789 In our study, no significant difference in mortality was noted
Heart rate (beats/min) 98.78 SD = 21.32 98.46 SD = 23.98 0.950 between the ESRD and non-ESRD group. This is in contrast with the
Temperature (F) 98.53 SD = 2.69 98.75 SD = 4.46 0.768
Respiratory rate (breaths/min) 20.71 SD = 4.13 19.63 SD = 4.78 0.278
study by Omar et al. who found that despite receiving lesser fluids, pa-
*WBC (×109/L) 14.10 (11.61) 17.70 (12.40) 0.167 tients with ESRD had lower mortality compared to those without
ESRD. However, the overall mortality rate in their study was much
Quantitative data are presented as mean and standard deviation (SD) except the ones with
asterisk. Due to the skewed distribution of data, the characteristics with asterisk are pre- higher, indicating that it was a sicker cohort compared to our study
sented as median with interquartile range in parenthesis. Abbreviations- ESRD- End [20]. Although patients with ESRD are known to have significantly
Stage Renal Disease, SBP-Systolic Blood Pressure, DBP- Diastolic Blood Pressure, MAP- higher mortality in sepsis compared to non-ESRD patients [16], in our
Mean Arterial Pressure, F- Fahrenheit, WBC- White Blood Cell. study, we found no significant difference in their mortality. It is note-
worthy that non-ESRD patients in our study had a significantly higher
The sub-group analysis revealed several interesting findings lactic acid, heart rate, higher ICU admission rate, and need for vasopres-
(Table 5). There was no significant difference in the need for vasopres- sors compared to the ESRD group. Moreover, non-ESRD patients had a
sor support, number of vasopressors required, rate of ICU admission, mean creatinine of 3.19 mg/dL indicating a significant burden of renal
ICU LOS, and hospital LOS. The potential complications of volume disease in the control group. This may reflect a higher severity of their
overload were not found to be higher in sub-group 2 as there was no illness and hence a high mortality rate.
significant difference in the rate of intubation or urgent dialysis The multivariate logistic regression analysis showed that patients
between sub-group 1 and sub-group 2. There was no significant differ- who received adequate fluid resuscitation in the first 6 h had signifi-
ence in mortality between sub-group 2 which received more fluids and cantly lower mortality, regardless of the presence of ESRD or not.
sub-group 1 which received less aggressive fluid resuscitation. Another interesting observation was that higher age and higher lactic
acid were independently associated with a higher mortality compared
5. Discussion to the presence of CHF, ESRD or CCI, indicating that age and lactic acid
could be important markers to identify mortality risk in septic ESRD pa-
Patients with ESRD are a small, but important subset of patients pre- tients on HD. These findings were very similar to a recent study by Lowe
senting to the ED with SeS or SS. The current SSC guidelines do not pro- et al. on dialysis dependent ESRD patients with SS which also found that
vide guidance on the amount of fluid resuscitation required in patients age and elevated lactic acid are strong independent markers of mortal-
with ESRD on HD presenting with SeS or SS. It is important to mention ity [23]. Some recent studies suggest serum lactic acid as a new emerg-
that patients with ESRD may have been underrepresented in the recent ing vital sign and a predictor of mortality in SS patients [23,25]. Our
trials on EGDT in sepsis. Although they were not specifically excluded study is one of the very few to show an association of lactic acid with
from the trials, only b3.4% of the patients enrolled were described to mortality in ESRD patients on HD with SeS or SS.
Sub-group analysis helps in understanding the effect of fluid resusci-
tation on patient management outcomes in patients with ESRD on HD.
Table 5
We found no difference in any of the secondary outcomes. This suggests
Sub-group analysis of the case group. Comparison of secondary outcomes between ESRD
patients who received b30 mL/Kg fluids (Sub-group 1) vs those who received ≥ 30 mL/Kg that 30 mL/Kg of initial fluid resuscitation is probably safe in patients
fluids (Sub-group 2). with ESRD on HD. It did not lead to any complications related to volume
overload or affect in-hospital mortality. These findings are consistent
Sub-group 1 Sub-group P-value
(80) 2 (24)
with those of Akhter et al., Ozuzun et al., and Lee et al. who also found
no direct complications and no increase in mortality with aggressive
Fluids received (mL/Kg) in the first 6 h of 14.77 43.40 b0.001
presentation SD = 9.64 SD = 12.23
fluid resuscitation in patients with ESRD presenting to the ED with SeS
Total amount of fluids (mL) in first 6 h of 1279.40 2856.30 b0.001 or SS [19,21,22]. We propose that physicians should consider the use
presentation SD = 984.70 SD = 814 of adequate fluid resuscitation in patients with ESRD on HD. Frequent
*Time to order antibiotics (Hours) 1.5 (1.75) 1 (1.5) 0.064 assessment of hemodynamic status in these patients and use of bedside
ICU admission rate 52 (65%) 17 (70.83%) 0.806
echocardiography can guide us in adequately resuscitating ESRD
*ICU LOS (Days) 5 (5.5) 5 (4) 0.480
Need for vasopressors 41 (51.25%) 15 (62.50%) 0.360 patients on HD presenting to the ED with SeS or SS.
Number of vasopressors 0.708 Our study has some limitations that are worth mentioning. One of
• 1 32 (78.05%) 13 (86.67%) the limitations is that it is a single-center retrospective study and not
• 2 9 (21.95%) 2 (13.33%) a multicenter prospective trial; this may limit the ability to generalize
Intubation rate within 24 h of presentation 4 (6.35%) 3 (16.67%) 0.179
the results. Since this was a retrospective study, the results might
for respiratory distress
*Length of mechanical ventilation (Days) 4 (10) 6 (4) 0.825 have been influenced by an uneven distribution of baseline characteris-
Need for urgent dialysis for volume 2 (2.56%) 0 (0%) 1.00 tics between the two groups, which we tried to minimize by conducting
overload a multivariate logistic regression and also by performing a subgroup
*Hospital LOS (Days) 8 (11) 8 (9.5) 0.608
analysis within the ESRD group. In our study, although all patients re-
Mortality 31 (38.75%) 10 (41.67%) 0.816
ceived crystalloids for fluid resuscitation for SeS or SS, we did not record
Quantitative data are presented as mean and standard deviation (SD) except the ones with the type of crystalloid received or the use of blood products or albumin
asterisk. Due to the skewed distribution of data, the characteristics with asterisk are pre-
sented as median with interquartile range in parenthesis. Abbreviations- ESRD- End
for other reasons. This could have confounding effects on the outcomes.
Stage Renal Disease, ICU- Intensive Care Unit, LOS- Length of Stay. However, the preferred choice of intravenous fluids for resuscitation in
P values in bold are statistically significant. SeS or SS at our institution was mostly normal saline, followed by ringer
162 K. Rajdev et al. / Journal of Critical Care 55 (2020) 157–162
lactate. Another limitation of our study is that we did not calculate the
APACHE score as a measure of severity of illness. Studies have shown
APACHE scores to be strong predictors of hospital mortality in septic pa-
tients [26,27]. Moreover, the inability of the subgroup analysis to show a
significant difference could be due to the overall small sample size for
subgroup analysis (N = 24 in higher fluid administration group vs 80
in lesser fluid administration group).
Despite the limitations, our study had a large sample size compared
to some of the previously mentioned studies in the literature and we
were able to highlight some key findings in this field that may be useful
in the management of patients with ESRD on HD presenting with SeS or
SS. In conclusion, we found that among patients presenting with SeS or
SS, fewer patients with ESRD compared to non-ESRD, received
guideline-based fluid resuscitation in the first 6 h. Patients with ESRD
on HD who received ≥30 mL/Kg fluids did not have a higher rate of com-
plications related to volume overload or in-hospital mortality compared
to ESRD patients on HD who received less fluid. Fluid resuscitation is the
cornerstone for the management of patients with SeS or SS. Our study
indicates that initial fluid resuscitation of 30 mL/Kg may be safe, or at
least not harmful, in patients with ESRD on HD and can potentially be
incorporated in the sepsis triage bundle in the ED. This could improve
compliance with the SSC guidelines and at the same time, provide clini-
cians an option of withholding fluids if clinically deemed appropriate. As
there is very limited literature available on patients with ESRD present-
ing with SeS or SS, we hope that our research will stimulate further
studies, including prospective trials, in this direction, to have a better
understating of the effect of fluid resuscitation in ESRD patients with
SeS or SS.
Financial disclosure
Authors have no financial disclosure.
Declaration of Competing Interest
Authors have no conflicts to disclose.
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