경희의학 : 제 32 권 제1 호 □ 증 례 □

J Kyung Hee Univ Med Cent : Vol. 32, No. 1, 2017

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Anesthetic Management of Pediatric Liver Transplantation for Langerhans Cell Histiocytosis with Central Diabetes Insipidus

: A Case Report

Seung-Ah Ryu1, Jae-Hyuk Lee1, Chan-Hee Lee1, Sun-Key Kim2

1Department of Anesthesiology and Pain Medicine, Seoul Medical Center, Seoul, 2Department of Anesthesiology and Pain Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea

Corresponding author: Sun-Key Kim, Clinical Instructor, Department of Anesthesiology and Pain Medicine, Asan Medical

Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpagu, Seoul 05505, KoreaTel: +82-2-3010-3876, Fax: +82-2-3010-6790

E-mail: ksk8325@amc.seoul.kr

INTRODUCTION

Langerhans cell histiocytosis (LCH) is a rare immu-

nologic disorder occurring mainly in childhood. It

involves the abnormal proliferation of histiocytes,

genotypically similar to Langerhans cells, in single or

multiple organs. Liver involvement manifests with

clinical, biochemical, and radiological features of

sclerosing cholangitis, and may progress to end-stage

chronic liver disease.(1) The presence of a large

volume of ascites in end-stage chronic liver disease can

cause intravascular volume depletion during anesthesia.

Central diabetes insipidus (DI) is characterized by

polyuria and elevation in serum sodium and osmolality.

Correction of hypernatremia requires replacement of

both water and electrolyte deficits, and it is important

to assess the patient’s plasma volume status as in the

setting of significant hypovolemia. It is also important

to determine the rate of correction, as there is a risk of

cerebral edema if the sodium level is corrected too

rapidly.

We report a case of a 3-year-old girl with LCH and

central DI, who underwent liver transplantation under

general anesthesia. We present details of the successful

management of the volume status and sodium level. To

our knowledge, this is the first report of pediatric liver

transplantation in a patient with LCH in Korea.

CASE REPORT

The female patient, born at 38 weeks gestation

weighing 3.02 kg, had no remarkable previous develop-

mental episode. She presented as a 2-year-old with

dermatitis seborrheica, polydipsia, polyuria, and

abdominal distention, and was diagnosed with LCH,

liver disease (classified as Child-Pugh class C and with

a pediatric end-stage liver disease score of 22) and

central DI (Fig. 1). The patient was treated with

chemotherapy for the LCH, and desmopressin for the

central DI. Her sodium level was poorly controlled

between the range of 131 to 159 mmol/L, and she

experienced seizure with drowsy mentality several

times due to the abrupt decrease in sodium level. She

− Seung-ah Ryu, et al：Anesthetic Management of Pediatric Liver Transplantation for Langerhans Cell Histiocytosis with Central Diabetes Insipidus −

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Fig. 1. The whole body magnetic resonance imaging

showed Langerhans cell histiocytosis involve-

ment in both distal femurs, liver cirrhosis with

large amount of ascites

had several episodes of variceal bleeding in the

gastrointestinal tract. The medical team considered her

suitable for orthotopic liver transplantation after achie-

ving complete remission from the LCH. However, the

LCH was refractory, and as the patient developed

severe jaundice during the chemotherapy, finally the

chemotherapy ceased. She was admitted for liver trans-

plantation workup and her abdominal circumference

was found to have increased by about 18 cm since she

was last discharged from our medical center. During

the workup, desmopressin treatment was interrupted

due to acute renal failure, which required continuous

renal replacement therapy; desmopressin was repeatedly

resumed for a few days to combat polyuria and

increased sodium levels, but was finally stopped.

Ascites were drained continuously via the peritoneal

dialysis catheter for 2 days before the operation to

avoid abrupt volume depletion during surgery.

At preanesthetic assessment, the patient’s weight was

14.5 kg and height was 89 cm. She was severely

jaundiced, with hepatosplenomegaly. Laboratory test

results were as follows: hemoglobin, 10.4 g/dL; white

blood cell count, 17.1 x 109/L; platelets, 66 x 10

9/L;

sodium, 156 mmol/L; potassium, 4.2 mmol/L; glucose,

97 mg/dL; creatinine, 0.31 mg/dL; albumin, 3.7 g/dL;

aspartate transaminase, 186 IU/L; alanine transaminase,

83 IU/L; total bilirubin, 112.4 mg/dL; ammonia, 765

mol/L; and troponin-I, 0.018 ng/mL. On imaging,

there was no evidence of a pituitary mass; there were,

however, right frontal and left parietal parenchymal

lesions, and brain involvement of LCH could not be

excluded, and there was evidence of sclerosing

cholangitis caused by involvement of LCH. Her mental

status was alert.

In the operating room, electrocardiograph, pulse

oximetry, cerebral oximetry, and bispectral index

monitors were applied. We also monitored arterial

blood pressure and central venous pressure by placing

intravascular catheters into the right femoral artery and

left internal jugular vein, respectively. Her vital signs

were as follows: systolic/diastolic arterial blood pressure,

71/43 mmHg; heart rate, 125 beats/min; and central

venous pressure, 9 mmHg. Arterial blood gas analysis

results as follows: pH, 7.50; PaCO2, 34 mmHg; PaO2,

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Table 1. Cahnges of Electrolytes and Vital Signs during Liver Transplantation Surgery in a 3-year-old Child with

Langerhans Cell Histiocytosis and Central Diabetes Insipidus

Before induction Preanhepatic phase Anhepatic phase After reperfusion

Electrolytes

Na+ (mmol/L) 148 149 148 148

K+ (mmol/L) 4.6 3.9 3.4 3.6

Ca2+ (mg/dL) 9.4 7.8 8.5 7.7

Vital sings

SBP/DBP (mmHg) 68/42 62/39-95/52 75/44-85/50 65/40-96/54

Heart rate (beats/min) 125 112-123 115-120 110-121

SBP: systolic arterial blood pressure, DBP: diastolic arterial blood pressure

87 mmHg; HCO3-, 22.6 mEq/L; SaO2, 97%. Electro-

lytes were as follows: sodium, 146 mmol/L; potassium,

4.0 mmol/L; calcium, 1.20 mmol/L; and glucose, 65

mg/dL. Hemoglobin was 9.9 g/dL and the hematocrit

was 29%.

General anesthesia was induced with thiopental 75

mg, rocuronium 20 mg, and fentanyl 15 g, and endo-

tracheal intubation was performed. Both breathing

sounds were equal and without rales. Anesthesia was

maintained with sevoflurane in 50% oxygen/air and

continuous fentanyl infusion.

The duration of the operation was 10 hours and 10

minutes, and the duration of anesthesia was 12 hours

and 15 minutes. The prehepatic, anhepatic, and neo-

hepatic phases were 7 hours and 10 minutes, 1 hour

and 5 minutes, and 4 hours, respectively. Postreper-

fusion syndrome did not develop.

After the induction of anesthesia, 600 mL of ascites

were drained via the peritoneal dialysis catheter. A

flow of ascites was observed in the operative field

throughout the operation. About 30 minutes after the

start of the operation, the patient’s systolic/diastolic

arterial blood pressure slowly dropped to 53/33 mmHg;

we therefore started a continuous infusion of norepi-

nephrine at a dose of 0.1 g/kg/min. Her systolic arterial

blood pressure rose within a few minutes and was then

stable at 80 mmHg for most of the operation. The

mean central venous pressure during the prehepatic,

anhepatic, and neohepatic phase was 4, 3, and 5

mmHg, respectively. Urine output during the pre-

hepatic, anhepatic, and neohepatic phase was 48 mL

(6.7 mL/h), 17 mL (16 mL/h), and 300 mL (75 mL/hr),

respectively. The total estimated ascites volume during

the entirety of the operation was 2 L. The level of

sodium during the prehepatic, anhepatic, and neohepatic

phase was 149, 148, and 148 mmol/L, respectively

(Table 1). The volumes of crystalloids administered

were as follows: 170 mL of 5% DNK3, 285 mL of

10% dextrose water, and 1.2 L of plasma solution. The

volume of 5% albumin administered was 2.5 L. Trans-

fused blood products were as follows: red blood cells,

250 mL; fresh frozen plasma, 40 mL; cryoprecipitate, 4

units; and platelet concentrates, 4units.

After the operation, the patient was transferred with

an endotracheal tube to the pediatric intensive care

unit; her weight had dropped by about 4 kg. She

developed polyuria and an elevated sodium level, and

therefore desmopressin treatment was commenced,

which restored normal urination and sodium levels. She

was extubated 2 days after the operation, and imaging

1 month later showed that there was no stenosis at the

portal vein anastomosis site. The patient developed no

new neurologic findings, and resumed oral feeding

without any problem. She was well at discharge.

− Seung-ah Ryu, et al：Anesthetic Management of Pediatric Liver Transplantation for Langerhans Cell Histiocytosis with Central Diabetes Insipidus −

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DISCUSSION

LCH is a rare disorder and most commonly charac-

terized by single or multiple osteolytic bone lesions of

infiltrated histiocytes with bean-shaped nuclei evident

at biopsy. These cells, along with lymphocytes, macro-

phages, and eosinophils, may infiltrate nearly every

organ (notably the skin, lymph nodes, lung, thymus,

liver, spleen, bone marrow, or central nervous system,

but not the heart and kidneys). The clinical presen-

tation of patients with LCH varies depending upon the

sites and extent of involvement. Acute disseminated

multisystem disease is most commonly seen in children

less than 3 years of age, while a more indolent disease

involving a single organ is more common in older

children and adults.(2) Liver disease has been reported

to occur in 16–36% of patients with LCH,(3) and

presents with histologically acute hepatitis with abnormal

histiocytes or severe, progressive cholestasis with a bile

duct lesion, and sclerosing cholangitis.(1) The cause of

liver cirrhosis in LCH is not well defined as several

mechanisms have been implicated; these include

histiocytic infiltration, extrinsic compression of the

common bile duct by adenopathy in the hepatic hilus,

histiocytic infiltration of the extrahepatic bile ducts,

drug-induced injury, total parenteral nutrition, and

primary sclerosing cholangitis.(4) Liver transplantation

in patients with LCH is controversial because of the

risk of recurrence of the underlying disease, which can

manifest as a viral, neoplastic, or autoimmune disease.(5)

However, one study asserts that liver transplantation is

the treatment of choice for LCH patients with

progressive sclerosing cholangitis, and that liver

transplantation should be performed as early as possible

in patients with severe hepatic damage.(6)

Central DI is rare in children and characterized by

decreased release of antidiurectic hormone, resulting in

a variable degree of polyuria. Central DI is a disease

caused by idiopathic DI most commonly,(7) and by

primary or secondary tumors or infiltrative diseases

(such as LCH),(8) neurosurgery, and trauma. During

the natural course of LCH, central DI occurs in about

one quarter of patients.(9) It is a syndrome charac-

terized clinically by excretion of abnormally large

volumes of free water,(10) resulting in solute-free

water loss in the urine and hypernatremia. Hyper-

natremia, especially, can cause severe perioperative

morbidity and mortality, and complications range from

headaches, weakness, neuromuscular irritability and

confusion, seizures, coma, or death.(11) Correction of

hypernatremia requires the administration of dilute

fluids to both correct the water deficit and replace

ongoing water losses, and also, when appropriate,

interventions to limit further water loss. In any child

with significant volume depletion, first management

steps should be directed toward ensuring cardiovascular

stability. It is recommended that the rate of correction

should not exceed a fall in sodium of greater than 0.5

mEq/L per hour.(12)

Ascites is defined as the pathologic accumulation of

fluid in the peritoneal cavity.(11) Also ascites is the

most common complication of cirrhosis, which is the

most common cause of ascites, accounting for approxi-

mately 85 percent of cases in the United States.(13)

The formation of ascites is governed by the same

principles as edema formation at other sites, including

net capillary permeability and hydraulic and oncotic

pressure gradients. Portal hypertension and the conse-

quences of vasodilatation are determining factors for

ascites formation in liver cirrhosis.(14)

It is important for the anesthesiologist to carefully

monitor the intravascular volume status and electrolyte

levels. In this case, the patient had liver cirrhosis

caused by LCH with central DI, and central DI results

in excretion of free water. Ascites accumulation is

wasting state of body water. Our patient required

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replacement of both water and electrolyte deficits. To

monitor and control the intravascular volume and

sodium level, we measured arterial blood pressure and

central venous pressure, and received electrolyte

readings from the laboratory, monitoring input and

output frequently. Systolic arterial blood pressure was

maintained at 80 ± 10 mmHg throughout the operation.

Central venous pressure fell suddenly at the start of the

operation, probably because the preoperative central

venous pressure was overestimated due to the ascites.

During the operation, central venous pressure was

maintained constantly at 4 ± 1 mmHg.

We had to consider which of several kinds of fluids

we would administer to the patient. The fluid we used

in anesthesia was plasma solution, 5% DNK3, 10%

dextrose water, 5% albumin; 5% DNK3 and 10%

dextrose water are used for controlling serum glucose

and potassium levels. Plasma solution is a balanced

crystalloid solution (containing sodium at 136 mEq/L)

that is used for volume replacement, but in our patient,

because of her central DI, a crystalloid solution alone

would not effectively increase the circulatory volume,

and would instead lead to generalized edema and cause

too rapid a correction of the sodium level. Albumin is

a colloid prepared from human venous plasma and the

sodium content in the 5% solution is 145±15 mEq/L,

with the usual concentration being 154 mEq/L. The

sodium level we administered, which was evaluated

just before induction of anesthesia, was 146 mmol/L,

and the range in sodium level of the patient’s

measurements during the operation was 142–148

mmol/L. Thus, the regimen that we used of crystalloid

with colloid was able to both correct the water deficit

and control the sodium level.

In conclusion, as demonstrated by this report, it is

very important to optimize the intravascular volume in

cases of water deficit caused by central DI and ascites.

Furthermore, it is also important to strictly control

elevated sodium levels by the administration of various,

well considered fluids.

ABSTRACT

Anesthetic Management of Pediatric Liver

Transplantation for Langerhans Cell

Histiocytosis with Central Diabetes

Insipidus

: A Case Report

Seung-Ah Ryu1, Jae-Hyuk Lee1,

Chan-Hee Lee1, Sun-Key Kim2

1Department of Anesthesiology and Pain Medicine,

Seoul Medical Center, Seoul, 2Department of Anesthesiology and Pain Medicine,

Asan Medical Center, University of Ulsan College of Medicine,

Seoul, Korea

A 3-year-old girl with Langerhans cell histiocytosis

and central diabetes insipidus underwent liver

transplantation under general anesthesia. On arrival at

the operating room, she has severe ascites and

hypernatremia. During the operation, she showed signs

of intravascular volume depletion due to third spacing

by ascites and an excessive urine output caused by the

central diabetes insipidus. The anesthesiologists ende-

avored to administer appropriate fluids to optimize the

volume status and inhibit too rapid correction of the

sodium level. The intraoperative sodium level range

was 142-148 mmol/L, and the central venous pressure

range was 3-5 mmHg. The operation was completed

without complications. Several days after the operation,

she was discharged without any significant problem.

Key Words: Central diabetes insipidus, Langerhans

cell histiocytosis, Liver transplantation

− Seung-ah Ryu, et al：Anesthetic Management of Pediatric Liver Transplantation for Langerhans Cell Histiocytosis with Central Diabetes Insipidus −

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