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Pediatric Hepatorenal Syndrome Treatment & Management

  • Author: Rajendra Bhimma, MB, MD, ChB, PhD, DCH (SA), FCP(Paeds)(SA), MMed(Natal); Chief Editor: Timothy E Corden, MD  more...
 
Updated: Mar 19, 2015
 

Medical Care

Close inpatient monitoring of patients with hepatorenal syndrome (HRS) may be needed.

Medical therapy, especially vasoconstrictor therapy, is used as a temporizing measure to improve renal function while the patient with hepatorenal syndrome (HRS) awaits liver transplantation, if the patient is an appropriate candidate.[3]

Medical management of coagulopathy may also be required. Administer medical or surgical therapy for variceal disease if necessary. Monitor for adverse effects of vasoconstrictor therapies. Promptly start antibiotic therapy if bacterial sepsis or spontaneous bacterial peritonitis is suspected.

As appropriate, provide plasma volume expansion with albumin for recurrent, diuretic-resistant ascites.[3] Administer antibiotics to prevent or treat spontaneous bacterial peritonitis.

Vasoconstrictor agents

Vasoconstrictors, such as the vasopressin analogs ornipressin and terlipressin,[12] and the alpha1-adrenergic agonists, norepinephrine[12] and midodrine, have been studied and have shown promising results in adult patients. In one study, octreotide, a potent splanchnic vasoconstrictor, was not beneficial as single therapy.

The vasopressin analogs both act on V1 vasopressin receptors in the vascular smooth muscle cells to cause splanchnic vasoconstriction and thus increase systemic and renal perfusion.

A few studies have shown beneficial effects of ornipressin combined with albumin or dopamine. Ornipressin is an effective vasoconstrictive agent but has severe ischemic adverse effects in 30-50% of adult patients. These include ischemic mesenteric mucosa, myocardial ischemia, and ventricular arrhythmias. Therefore, it is not currently recommended as treatment for hepatorenal syndrome.

Terlipressin, a vasopressin analogue, has shown potential benefit in the treatment of HRS. Patients given terlipressin had a 50-75% response rate defined as an improved glomerular filtration rate (GFR) to more than 40 mL/min. GFR typically remains below normal, but this therapy provides a bridge to liver transplantation and improves the prognosis after transplantation. Most studies demonstrated an improved response rate with the addition of an albumin infusion to the terlipressin infusion. About 15% of patients have a recurrence after the drug is withdrawn, but most patients respond to retreatment. Terlipressin is administered in an intravenous (IV) bolus every 4 hours for as long as 15 days. Ischemic adverse effects are rare (5-10%) and milder than those of ornipressin. However, this drug is costly and has somewhat limited availability.

Alpha1-adrenergic agonists

Alpha1-adrenergic agonists (eg, noradrenalin, midodrine) are alternatives to the vasopressin analogs and offer the advantage of current availability in the United States and several other countries at a lower cost. They have been most extensively studied in patients with type 2 hepatorenal syndrome (HRS), whereas terlipressin has been evaluated more extensively in type 1 hepatorenal syndrome. The incidence of adverse effects (usually ischaemia) that compels discontinuation of treatment is about 12%. Data from an unblinded, pilot study suggested that noradrenalin was as effective as terlipressin but was associated with increased risk of ischemic events. Another study reported similar beneficial results; however, 2 patients had ventricular arrhythmias. Further studies are needed to evaluate the use of alpha1-adrenergic agonists as potential treatment for HRS.

Paracentesis

Paracentesis may be used in patients with refractory ascites, especially if they are experiencing respiratory embarrassment. Repeated large volume or total volume paracentesis can be used together with plasma volume expanders. Failure to replace losses with a volume expander leads to the development of postparacentesis circulatory syndrome in some patients. Plasma renin activity rises, followed by an insidious rise in serum creatinine over a period of months and the onset of type II hepatorenal syndrome. The pathophysiology of this complication is not fully understood but it is postulated the paracentesis results in peripheral vasodilatation that enhances effective arterial underfilling, and therefore requires acute volume expansion.

Treatment options

Hemodialysis (HD), continuous renal replacement therapy (CRRT), and extracorporeal albumin dialysis (ECAD) are possible treatment options for patients with hepatorenal syndrome.[13] These options have not been reported sufficiently in the literature to support their consistent use. Patients with hepatorenal syndrome historically do not tolerate HD, and deaths during dialysis have been reported. At present, HD is recommended for medically resistant hyperkalemia or severe fluid overload. CRRT remains a potential option for certain patients with hepatorenal syndrome; however, the literature is limited to only case reports.

A more recent method used for the treatment of hepatorenal syndrome is extracorporeal albumin dialysis (ECAD). The procedure uses a cell-free albumin-containing dialysate that is recirculated and perfused through charcoal and anion exchange columns (molecular absorbent recycling system [MARS]). The system is also connected to a hemodialysis or hemoperfusion apparatus. ECAD enables the removal of albumin-bound substances, including bilirubin, bile acids, aromatic amino acids, medium chain fatty acids, and cytokines. ECAD decreases serum creatinine levels but whether or not this effect is due to a true improvement of renal function or simply to the filtration process is unknown.

ECAD has also been reported to improve systemic hemodynamics as indicated by an increase in arterial pressure and systemic vascular resistances and a decrease in cardiac output, plasma renin activity, and norepinephrine levels. To date, these data are based on a few studies of ECAD in cirrhotic patients with hepatorenal syndrome, mainly in patients with type 2 hepatorenal syndrome. Studies regarding the effect of ECAD on survival in patients with type 1 hepatorenal syndrome include too few patients to make definite conclusions.

Consultations

Consultations with the following specialists are indicated:

  • Nephrologist
  • Gastroenterologist
  • Transplant surgeon
  • Vascular surgeon

Transfer

Transfer to a tertiary care center specializing in liver transplantation may be required to manage this complex disease.

Diet

A low-sodium diet is generally useful for all patients with hepatorenal syndrome, as is fluid restriction because of the renal impairment.

Decreased sodium intake can reduce the severity of the ascites in some patients and can lower the incidence of dilutional hyponatremia.

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Surgical Care

Surgical options for patients with hepatorenal syndrome include the transjugular intrahepatic portosystemic shunt (TIPS) procedure and liver transplantation. Peritoneovenous shunting and portosystemic shunting have been attempted in hepatorenal syndrome, but their effectiveness in the treatment of hepatorenal syndrome has not been demonstrated.

A peritoneovenous shunt allows ascitic fluid to pass from the peritoneal cavity back into the systemic circulation. This passage may increase cardiac output and expand the intravascular compartment, decreasing vasoconstrictor activity in patients with hepatorenal syndrome. Improvement in renal blood flow and increased GFR follows. No controlled studies have shown improved survival with this procedure; however, isolated reports have shown a reversal of hepatorenal syndrome.

Portacaval anastomosis is not the standard of care for patients with hepatorenal syndrome because of the high morbidity and mortality risks associated with these procedures.

The TIPS procedure (see the image below) is used as an alternative in treating patients with bleeding esophageal varices that do not respond to standard therapy and in patients with refractory ascites.

Basic transjugular intrahepatic portosystemic shun Basic transjugular intrahepatic portosystemic shunt (TIPS) procedure. A curved catheter is placed into the right hepatic vein.

TIPS can be used as a bridge to prolong the survival of patients with type 2 HRS until liver transplantation can be performed. This procedure may decrease portal pressure, which decreases the systemic and renal vasoconstrictor systems. It increases the GFR in 60% of patients with hepatorenal syndrome. However, median survival after TIPS is only 2-4 months.

Contraindications are severe liver failure and severe hepatic encephalopathy because the procedure can lead to irreversible liver failure and chronic, disabling hepatic encephalopathy.

TIPS is currently recommended for patients who appear to be eligible for liver transplantation but in whom vasoconstrictor medical therapy fails. TIPS should not be considered as monotherapy in hepatorenal syndrome. There is delayed recovery of kidney function following TIPS (within 2-4 wk), unlike vasoconstrictor therapy, in which kidney function recovers much faster (1-2 wk).[14, 15]

Significant suppression of the endogenous vasoactive systems, particularly the renin angiotensin system, and a decrease in serum creatinine levels has been observed, although this was slower than that seen in patients treated with terlipressin plus albumin. The recurrence of HRS is rare, provided no shunt malfunction occurs. Hepatic encephalopathy is a frequent complication of TIPS but has been adequately managed using medical therapy. TIPS almost always induces a reduction of ascites volume. Resolution of type 1 HRS by TIPS can improve survival. Increased length of survival has been noted with sequential treatment using vasoconstrictors and albumin infusions followed by TIPS. A recent study has shown TIPS to improve outcome post liver transplantation, probably through improving kidney function.[16]

Liver transplantation is the treatment of choice for patients with hepatorenal syndrome because it cures the underlying liver disease and thus allows renal function to recover secondary to improved perfusion after transplantation.

Most patients with hepatorenal syndrome do not survive long enough or are not candidates for liver transplantation. Most centers advocate vasoconstrictor therapy before the transplantation since this decreases post transplantation morbidity and mortality. Combined liver and kidney transplantation is rarely recommended because the renal failure is functional and reversible.

Renal function may further deteriorate after transplantation, and more than one third of patients require dialysis. Because renal impairment may be secondary to the increased nephrotoxic effect of calcineurin inhibitors (cyclosporin and tacrolimus), these agents should be used 48-72 hours after transplantation, when renal function is expected to improve. The main limitation of liver transplantation is due to the shortage of donor organs. Also, patients with type 1 hepatorenal syndrome often die before transplantation. Combined liver-kidney transplantation is appropriate only for patients who have a low likelihood of recovery of kidney function.

Controversy still exists regarding the best modality of dialysis in orthotopic liver transplantation candidates. Continuous renal replacement therapy is better tolerated than intermittent hemodialysis as evidenced by better cardiovascular stability, gradual correction of hyponatremia, and less fluctuation in intracranial pressure.[17] The choice of renal replacement therapy is dictated by hemodynamic stability and severity of illness and should be tailored to individual patients.[6]

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Contributor Information and Disclosures
Author

Rajendra Bhimma, MB, MD, ChB, PhD, DCH (SA), FCP(Paeds)(SA), MMed(Natal) Associate Professor of Pediatrics, Principal Specialist, Department of Pediatrics and Child Health, Nelson R Mandela School of Medicine, University of KwaZulu-Natal, South Africa

Rajendra Bhimma, MB, MD, ChB, PhD, DCH (SA), FCP(Paeds)(SA), MMed(Natal) is a member of the following medical societies: American Association for the Advancement of Science, International Society of Nephrology, South African Medical Association, South African Paediatric Association, South African Transplant Society, International Pediatric Transplant Association

Disclosure: Nothing to disclose.

Specialty Editor Board

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

Barry J Evans, MD Assistant Professor of Pediatrics, Temple University Medical School; Director of Pediatric Critical Care and Pulmonology, Associate Chair for Pediatric Education, Temple University Children's Medical Center

Barry J Evans, MD is a member of the following medical societies: American Academy of Pediatrics, American College of Chest Physicians, American Thoracic Society, Society of Critical Care Medicine

Disclosure: Nothing to disclose.

Chief Editor

Timothy E Corden, MD Associate Professor of Pediatrics, Co-Director, Policy Core, Injury Research Center, Medical College of Wisconsin; Associate Director, PICU, Children's Hospital of Wisconsin

Timothy E Corden, MD is a member of the following medical societies: American Academy of Pediatrics, Phi Beta Kappa, Society of Critical Care Medicine, Wisconsin Medical Society

Disclosure: Nothing to disclose.

Additional Contributors

G Patricia Cantwell, MD, FCCM Professor of Clinical Pediatrics, Chief, Division of Pediatric Critical Care Medicine, University of Miami Leonard M Miller School of Medicine/ Holtz Children's Hospital, Jackson Memorial Medical Center; Medical Director, Palliative Care Team, Holtz Children's Hospital; Medical Manager, FEMA, South Florida Urban Search and Rescue, Task Force 2

G Patricia Cantwell, MD, FCCM is a member of the following medical societies: American Academy of Hospice and Palliative Medicine, American Academy of Pediatrics, American Heart Association, American Trauma Society, National Association of EMS Physicians, Society of Critical Care Medicine, Wilderness Medical Society

Disclosure: Nothing to disclose.

Acknowledgements

The author would like to thank Mr. Duran Ramsuran and the staff of Medscape Drugs & Diseases for the help in reviewing this article.

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Basic transjugular intrahepatic portosystemic shunt (TIPS) procedure. A curved catheter is placed into the right hepatic vein.
 
 
 
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