The Journal of Emergency Medicine, Vol. 52, No. 4, pp.

e149–e152, 2017
Ó 2016 Elsevier Inc. All rights reserved.
0736-4679/$ - see front matter

http://dx.doi.org/10.1016/j.jemermed.2016.07.089

Clinical
Communications: Pediatric

ASSESSMENT OF VOLUME STATUS AND APPROPRIATE FLUID REPLENISHMENT

Pierluigi Marzuillo, MD,* Stefano Guarino, MD,* Andrea Apicella, MD,* Rosaria Marotta, MD,* Vincenzo Tipo, MD,†
Laura Perrone,* Angela La Manna, MD,* and Giovanni Montini‡
*Department of Woman, Child and of General and Specialized Surgery, Seconda Università degli Studi di Napoli, Napoli, Italy, †Pediatric
Emergency Department, Azienda Ospedaliera di Rilievo Nazionale Santobono-Pausilipon di Napoli, Napoli, Italy, and ‡Pediatric Nephrology
and Dialysis Unit, Department of Clinical Sciences and Community Health, University of Milan, Fondazione IRCCS Ca’ Granda-Ospedale
Maggiore Policlinico, Milano, Italy
Reprint Address: Pierluigi Marzuillo, MD, Department of Woman, Child and of General and Specialized Surgery, Seconda Università degli Studi
di Napoli, Via Luigi De Crecchio 2, Napoli 80138, Italy

, Abstract—Background: When the permeability of the apy instead of crystalloid and 20% albumin; and 3) pay
glomerular filtration barrier increases, leading to protein- attention when using furosemide; it should only be adminis-
uria, nephrotic syndrome (NS) occurs. First episodes or re- tered after albumin infusion or after hypovolemia
lapses of NS can be concurrent with acute gastroenteritis correction. Ó 2016 Elsevier Inc. All rights reserved.
(AGE) infections. This condition can cause further deterio-
ration of the hypovolemic state, as intravascular water is , Keywords—nephrotic syndrome; hypovolemic shock;
lost through both AGE-related vomiting/diarrhea and NS- hypoalbuminemia; furosemide; dehydration
related fluid shifting into the interstitium. In this case report,
we wish to raise the issues about the difficult management of
INTRODUCTION
children presenting with both NS and AGE. Case Report:
We report two cases characterized by concurrence of NS
and AGE. Despite our intervention, case #1 required dial- Nephrotic syndrome (NS) is a kidney disease character-
ysis, whereas in the case #2 we restored the patient’s liquid ized by an increased permeability of the glomerular filtra-
homeostasis. Why Should an Emergency Physician Be tion barrier leading to proteinuria, hypoalbuminemia,
Aware of This?: No guidelines helping general physicians edema, and hyperlipidemia, and it has an incidence of
in the management of children presenting with both NS 1–3 per 100,000 children < 16 years of age per year
and AGE are available in the literature. However, it is com- (1,2). Acute and life-threatening complications can occur
mon for these patients to seek the first line of treatment at in NS-affected children, such as hypovolemia/hypoten-
emergency departments. In these patients, restoring the sion, invasive bacterial infection, and thrombosis (1,2).
liquid homeostasis is a challenge, but some key points can
Acute gastroenteritis (AGE) is a major cause of illness
help the physicians with first-line management: 1) carefully
worldwide, with 3–5 billion cases and nearly 2 million
evaluate the signs of hypovolemia (edematous state can be
misleading); 2) bear in mind that—in hypovolemic, severely deaths occurring each year in children under 5 years of
hypoalbuminemic (serum albumin levels < 2 g/dL) NS chil- age, mostly in the developing world (3,4). Dehydration,
dren—initial fluid administration should be followed by a metabolic acidosis, and electrolyte disturbance are the
20% albumin infusion if oligoanuria persists; intravenous most important and dangerous AGE-related complica-
4.5% albumin may be a valid alternative as a first-line ther- tions (4). Careful management with oral or intravenous

RECEIVED: 30 May 2016; FINAL SUBMISSION RECEIVED: 13 July 2016;

e149
e150 P. Marzuillo et al.

fluids can help to prevent them (4). NS may start or relapse which had been preceded by gradual peripheral edema
during AGE in childhood (5,6). Moreover, infections and weight gain of 1 kg (his weight 1 month prior was
could represent a risk factor for acute kidney injury 10.7 kg; at our observation it was 11.710 kg). Oral rehy-
(AKI) in patients with NS (7). It is common for patients dration was difficult due to vomiting. The amount of the
presenting with both NS and AGE to seek medical treat- previous urine volume was unknown. He appeared abnor-
ment at emergency units. Both evaluating and treating mally sleepy with sunken eyes, and showed pallor, pe-
the hypovolemic state of a patient losing water through ripheral edema with the fovea sign, bilateral hydrocele,
both AGE-related vomiting/diarrhea and NS-related fluid and a refill time of 3 s. Blood pressure was 75/40 mm
shifting into the interstitium is a challenge for emergency Hg. Blood tests and urinalysis showed low sodium levels
physicians. Also, the timing of albumin and furosemide (125 mEq/L), hyperlipidemia (cholesterol 406 mg/dL and
administration is a difficult choice. No indications or triglycerides 530 mg/dL), hypoalbuminemia (1.50 g/dL),
guidelines are available in the literature. In this case and proteinuria (urinary protein/urinary creatinine ratio:
report, we want to raise the issues about the difficult man- 11.8; n.v. < 0.25). Creatinine and urea levels were 0.27
agement of children presenting with both NS and AGE and 34 mg/dL, respectively. The clinical and biochemical
and give to the emergency physicians some elements evidence was suggestive of a first episode of NS concur-
helping in the first-line management of these patients. rent with AGE. Firstly, i.v. 20 mL/kg 0.9% NaCl in
20 min was administered, with apparent improvement
CASE #1
in the patient’s general condition. Sixty mg/m2/day pred-
nisone and 3 mg/kg/day aspirin were started. Secondly,
A 9-year-old girl affected by steroid- and cyclosporine-
i.v. 0.9% NaCl (900 mL/24 h) was continued over the
dependent NS, receiving cyclosporine alone (4 mg/kg/
following 4 days to restore and maintain the euvolemic
day) during the last 3 years, presented with both NS
state. Each day (including the first day), he received a
relapse and AGE infection. She showed incoercible vom-
3-h i.v. 2.5 mL/kg/die 20% albumin followed by a 1-
iting (not responsive to two doses of sublingual ondanse-
mg/kg furosemide bolus. Saline administration was sus-
tron) and diarrhea (up to 10 discharges/day) for 4 days
pended during the albumin infusion.
and NS relapse for 2 days prior to coming to our unit.
After 4 days of therapy, the hypovolemic state and the
At the AGE onset, renal function was normal (creatinine
AGE-related vomiting and diarrhea resolved. The weight
0.6 mg/dL). She was receiving prednisone (60 mg/m2/
was 11.4 kg. Intravenous therapy was stopped and daily
day) since the NS relapsed. Physical examination re-
oral corticosteroid therapy continued. The serum creati-
vealed drowsiness, tachycardia (118 beats/min), cold
nine values always appeared in the normal range.
hands and feet, and refill time of about 2 s. She reported
only one, low-quantity micturition during the last 18 h,
DISCUSSION
and presented weight gain of 0.8 kg in absence of periph-
eral edema (the weight 1 week prior was 35.2 kg; at our
The rehydration of a patient with concomitant AGE and
observation it was 36 kg). Blood pressure was 90/
NS who is then not able to retain fluids in the vessels
50 mm Hg. Blood tests showed creatinine 4.1 mg/dL, so-
due to hypoalbuminemia, raises issues among clinicians
dium 139 mEq/L, potassium 6.1 mEq/L, urea 150 mg/dL,
because the conventional rehydration schemes alone are
and albumin 1.8 g/dL. Echo-color Doppler sonography
not sufficient to restore the euvolemic state. In this situa-
excluded renal vein thrombosis, and low-dose aspirin
tion, the intravascular volume is further depleted and the
was started to prevent it. As NS- and AGE-related hypo-
dehydration can become severe. Abnormal skin turgor
volemia was evident, we administered i.v. 20 mL/kg 0.9%
represents one of the most useful predictors of 5% or
NaCl in 1 h followed by 2.5 mL/kg 20% albumin in 3 h
more dehydration, but in a patient with NS, the edema-
and then 1 mg/kg of furosemide as a bolus. Despite our
tous state can partially complicate the dehydration evalu-
treatment, 6 h after admission she had passed only
ation (8). Therefore, a careful detection of all the signs of
66 mL (0.22 mL/kg/h) of urine, and levels of creatinine,
dehydration is fundamental, and a proper and timely
potassium, and urea were 4.45 mg/dL, 6.4 mEq/L and
treatment could reduce the risk of a possible evolution
250 mg/dL, respectively. Therefore, despite hypovolemia
to AKI (7).
correction, the acute renal failure seemed unresponsive to
In case #1, the peripheral edema was not marked,
medical treatment and required dialysis. Renal function
despite the relapsing NS, because the vomiting-related
was restored after 15 days.
hypovolemia limited fluid shift into the interstitium.
CASE #2 The delay (4 days after the onset of symptoms) in coming
to the emergency department (ED) possibly led to acute
A 3-year-old boy presented with AGE-related incoercible renal failure. Nephrotoxic medication exposure has
vomiting and diarrhea (up to 8 discharges/day, for 1 day), been identified as a risk factor for AKI in NS patients;
Acute Gastroenteritis in Nephrotic Syndrome e151

therefore, it is possible that the cyclosporine treatment i.v. 4.5% albumin solution (10–20 mL/kg in 3–4 h) poten-
accelerated the acute renal failure (7). For this reason, it tially followed by furosemide (but without previous intra-
could be reasonable to stop cyclosporine in a dehydrated venous NaCl 0.9% administration) could be considered,
NS patient until circulation is restored. Interestingly, with the aim of shifting liquids from the interstitium to
blood tests at the AGE onset showed normal creatinine the vessels and eliminating excess fluids and salts, thus
levels, demonstrating a subsequent rapid decline of renal maintaining the euvolemic state.
function. Patient 2 was severely hypovolemic. In this
case, our intervention was able to restore liquid homeo- WHY SHOULD AN EMERGENCY PHYSICIAN BE
stasis, and the renal function remained normal. This pa- AWARE OF THIS?
tient did not present other risk factors for AKI except
for the hypovolemia. In both cases, we administered furo- No guidelines helping general physicians in the manage-
semide only after the patient had been adequately rehy- ment of children presenting with both NS and AGE are
drated or albumin had been administered (9). available in literature. However, it is common for these
Low blood pressure, high refill time, sunken eyes, patients to seek the first line of treatment in EDs.
pallor, cold hands and feet, and drowsiness are the signs Restoring the liquid homeostasis in this kind of patient
of hypovolemia to look out for when evaluating the hy- is difficult, but as emergency physicians, some key points
dration state in an edematous patient with NS. Moreover, to help in the first-line management should be kept in
clinicians should be aware that in these patients, weight is mind: 1) carefully evaluate the signs and symptoms of hy-
not a useful tool to evaluate the dehydration degree povolemia (edematous state can be misleading, and
because paradoxical weight gain is possible despite the weight is not a useful tool to evaluate the dehydration de-
dehydration (Figure 1). The first step in the management gree); 2) bear in mind that—in hypovolemic, severely hy-
of these patients is to avoid severe hypovolemia through poalbuminemic (serum albumin levels < 2 g/dL) NS
rapid liquids administration, even if there are clinical children—initial fluid administration should be followed
signs of edema. However, if hypoalbuminemia is present, by a 20% albumin infusion if oligoanuria persists; intra-
the fluids administered could shift into the interstitium. venous 4.5% albumin may be a valid alternative as a
Therefore, after first resuscitating fluid administration, first-line therapy instead of crystalloid and 20% albumin;
i.v. 20% albumin infusion (1.25–5 mL/kg in 3–4 h) fol- and 3) pay attention when using furosemide, it should be
lowed by furosemide (1 mg/kg, during the second half administered only after albumin infusion and then after
or at the end of the albumin infusion) or, alternatively, hypovolemia correction.

Figure 1. Variation of % body weight of patients 1 and 2 prior to the onset of both nephrotic syndrome (NS) and acute gastroen-
teritis (AGE), and at admission, compared with that expected for different degrees of dehydration due to AGE alone.
e152 P. Marzuillo et al.

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