Journal of Current Medical Research and Practice

ORIGINAL ARTICLE
Year
: 2020  |  Volume : 5  |  Issue : 1  |  Page : 71--78

Clinical audit on management of hepatic encephalopathy in children admitted to Gastroenterology and Hepatology Unit of Assiut University Children Hospital


Johnny M Maken, Fatma A Ali, Nagla H Ibrahim 
 Department of Pediatrics, Faculty of Medicine, Assiut University, Assiut, Egypt

Correspondence Address:
Johnny M Maken
Department of Pediatrics, Faculty of Medicine, Assiut University, Assiut
Egypt

Abstract

Introduction Hepatic encephalopathy (HE) is an important metabolic disturbance in children. It is defined as a spectrum of neuropsychiatric abnormalities in patients with liver dysfunction, after exclusion of brain disease. Patients and methods A clinical audit on management of HE was applied according to the guideline protocol used in Gastroenterology and Hepatology Unit of Assiut University Children Hospital. The study included 52 children with HE who were admitted to Gastroenterology and Hepatology Unit over 1-year period from the 1st of March 2016 to the 28th of February 2017. Results Detailed history intake was recorded in most cases, except history of drug intake, which was not recorded in 23.15% of cases; history of reversal of sleep rhythm, which was not recorded in 17.3% of cases; and history of behavioral changes, which was not recorded in 9.6% of cases. Data of examination were recorded in most cases, except for fetor hepaticus, which was recorded in 42.3% of cases; asterixis, which was recorded in 36.5% of cases; and neurological examination, which was recorded in 91.2% of cases. Basic and mandatory investigations in the diagnosis of HE were done. The standard treatment of HE has been applied except admission to the ICU and prophylactic endotracheal intubation were not applied. Moreover, oral branched-chain amino acids and rifaximin were not given. Conclusion The international guidelines for the management of HE have been followed by the Gastroenterology and Hepatology Unit of Assiut University Children Hospital in most treatment lines and that some of the default is owing to poor-resource setting and lack of medication.



How to cite this article:
Maken JM, Ali FA, Ibrahim NH. Clinical audit on management of hepatic encephalopathy in children admitted to Gastroenterology and Hepatology Unit of Assiut University Children Hospital.J Curr Med Res Pract 2020;5:71-78


How to cite this URL:
Maken JM, Ali FA, Ibrahim NH. Clinical audit on management of hepatic encephalopathy in children admitted to Gastroenterology and Hepatology Unit of Assiut University Children Hospital. J Curr Med Res Pract [serial online] 2020 [cited 2020 Mar 30 ];5:71-78
Available from: http://www.jcmrp.eg.net/text.asp?2020/5/1/71/277503


Full Text



 Introduction



Hepatic encephalopathy (HE) is an important metabolic disturbance in children[1]. It is defined as a spectrum of neuropsychiatric abnormalities in patients with liver dysfunction, after exclusion of brain disease[2]. It is characterized by personality changes, intellectual impairment, and a depressed level of consciousness[3]. An important prerequisite for the syndrome is diversion of portal blood into the systemic circulation through portosystemic collateral vessels. HE is also described in patients without cirrhosis with either spontaneous or surgically created portosystemic shunts. The development of HE is explained, to some extent, by the effect of neurotoxic substances, which occurs in the setting of cirrhosis and portal hypertension[4]. The prevention of episodes of HE is an important goal in the treatment of patients with liver disease[5].

Controlling precipitating factors in the management of HE is of paramount importance, because nearly 90% of patients can be treated with just correction of the precipitating factor. Careful attention to this issue is still the cornerstone of HE management[6].

The most important component of managing a child with HE is basic intensive care with regulation of fluid status, glucose, and electrolyte homeostasis. Specific management includes measures to reduce serum ammonia concentrations, prevention, and prompt treatment of complications. Methods to reduce ammonia target various steps in its metabolism. This includes reducing its production and absorption from the intestine and promoting its metabolism in the liver[7].

 Aim of the Work



The aim is to assess how much the adapted protocols of management of HE were applied at Gastroenterology and Hepatology Unit of Assiut University Children Hospital.

 Patients and Methods



The present study was conducted in Assiut University Children Hospital on all children with HE admitted to Gastroenterology and Hepatology Unit. The present study included 52 children with HE who were admitted to Gastroenterology and Hepatology Unit of Assiut University Children Hospital over 1-year period from the 1st of March 2016 to the 28th of February 2017. Actually my Master Thesis was a clinical audit that does not need consent statement as all our work was on medical records only.

The following items were taken:

History:

History of neonatal ICU admissionHistory of neonatal jaundiceHistory of constipationHistory of gastrointestinal bleedingHistory of vomiting or diarrheaHistory suggestive of systemic infectionHistory of drug intakeHistory of previous surgeryHistory of previous or current liver diseaseHistory of yellowish discoloration of scleraHistory of change of color of urine or stoolHistory of bleeding tendencyHistory of convulsionHistory of reversal of sleep rhythmHistory of behavioral changesHistory of disturbance of conscious level

Examination:

General examination: conscious level, jaundice, pallor, cyanosis, and fetor hepaticusVital signs: pulse, blood pressure, temperature, and respiratory rateUpper and lower limb examination:Asterixis (flapping tremors of the hand): lower limb edemaChest examinationCardiac examinationNeurological examinationAbdominal examination: hepatomegaly, splenomegaly, and ascites

Investigations:

Complete blood countProthrombin time and prothrombin concentrationLiver function testsKidney function tests and electrolytesBlood glucose levelBlood gasesHepatitis markersUrine analysisElectroencephalography (EEG)Abdominal ultrasoundBlood cultureSerum ammonia level

Treatment:

General measures:

ICU (in grades 3 and 4 HE)Insertion of nasogastric tube (in comatosed patients)Insertion of urinary catheterProphylactic endotracheal intubation (in severe HE)EnemasEmpirical antibioticsStop gastrointestinal tract bleeding (in cases with gastrointestinal tract bleeding)Stop drugs precipitating HE (in cases with history of drug intake)Restriction of protein (in case of acute liver failure and inborn error of metabolism)

Specific measures:

Lactulose (oral, nasogastric tube, or enema)NeomycinMetronidazoleRifaximinL-ornithine L-aspartate (Hepamerz)Branched-chain amino acid supplementationZinc 8-L-carnitine.

 Results



The present study included 52 children with HE who were admitted to Gastroenterology and Hepatology Unit of Assiut University Children Hospital over 1-year period from the 1st of March 2016 to the 28th of February 2017. A total of 36 cases were males and 16 cases were females with age range from 4 months to 15 years.

[Table 1] shows that 69.2% were males and 30.8% were females, with age range from 4 months to 15 years.{Table 1}

[Table 2] shows that history of neonatal ICU was recorded in 100% of cases and that 82.7% of cases were asked about history of neonatal jaundice. Regarding history of precipitating factors of HE, most factors were recorded by resident doctors in 100% of cases but history of drug intake was recorded in 76.9% of cases. Overall, 100% of cases were asked about history of previous or recurrent liver disease. History suggestive of liver disease such as history of jaundice, yellowish discoloration of urine and stool, and bleeding tendency was fully recorded. Moreover, 82.7% of cases were asked about history of reversal of sleep rhythm and 90.4% of cases were asked about history of convulsion ([Figure 1] and [Figure 2], [Table 3]).{Figure 1}{Figure 2}{Table 2}{Table 3}

[Table 4] shows that assessment of conscious level, general examination, vital signs measurements, upper and lower limb examination, chest examination, and cardiac and abdominal examination were recorded in 100% of cases. Overall, 42.3% of cases were examined for presence of fetor hepaticus, 36.5% of cases were examined for presence of flapping tremors of the hand, and 13.5% of cases were examined for presence of palmar erythema. Neurological examination was recorded in 91.2% of cases [Table 5].{Table 4}{Table 5}

[Table 6] shows that 28.9% of cases had grade 1 HE, 32.7% of cases had grade 2, 17.3% of cases had grade 3, and 21.1% of cases had grade 4 HE [Figure 3].{Figure 3}{Table 6}

[Table 7] shows that complete blood count, prothrombin time, prothrombin concentration, liver function tests, kidney function tests, electrolytes, blood glucose level, blood gases, hepatitis markers, and abdominal ultrasound were done in 100% of cases. Urine analysis was done in 71.2% of cases. EEG was done in six cases, which were the cases that had convulsion. Blood culture was done in 10 cases which were the only indicated cases (cases that had symptoms or signs suggestive of sepsis). Serum ammonia level was not done in any case [Table 8].{Table 7}{Table 8}

[Table 9] shows that no case of grade 3 or 4 HE was admitted to ICU (instead they all were admitted at Gastroenterology Intermediate Care Unit), and no case of them had prophylactic endotracheal intubation. Insertion of nasogastric tube was done in 100% of cases, but insertion of urinary catheter was done in 40 cases. Enemas, empirical antibiotics, lactulose, neomycin, and L-ornithine L-aspartate (Hepamerz) were given in 100% 0f cases. Stopping of gastrointestinal bleeding and stopping of drugs precipitating HE occurred in 100% of indicated cases. Metronidazole was given in 5.8% of cases, branched-chain amino acid supplementation was given in 7.7% of cases, zinc was given in 17.3% of cases, and L-carnitine was given in 4% of cases, but rifaximin was not given at all.{Table 9}

 Discussion



Regarding history intake, most data of the history were fulfilled.

Controlling precipitating factors in the management of HE is of paramount importance, because nearly 90% of patients can be treated with just correction of the precipitating factor[6]. Regarding history of precipitating factors of HE in the present study, data about history of constipation, gastrointestinal bleeding, fluid loss, and systemic infection were recorded in 100% of cases except history of drug intake which was recorded in only 76.9% of cases. Rockey et al.[8] reported that a careful drug history should include listing of all agents taken, the time period involved, and the quantity or dose ingested. Paracetamol is usually well tolerated in prescribed dose, but overdose is the most common cause of drug-induced liver disease and acute liver failure worldwide[9]. Therefore, it is very important to take in consideration the importance of history of drug intake in children with HE, because HE may be a reversible disease in this condition. It is also important to do health education about the risk of abuse of antipyretics. In the present study, data about history of previous or current liver disease were recorded in 100% of cases. History suggestive of liver cell failure was recorded in 100% of cases. Regarding clinical symptoms of HE in the studied cases, history of disturbance of conscious level was recorded in 100% of cases, history of behavioral changes or abnormal movement was recorded in 90.4% of cases, history of reversal of sleep rhythm was recorded in 82.7% of cases, and history of convulsion was recorded in 90.4% of cases (only 12.6% of recorded cases had history of convulsions). In the case of minimal HE, there may not be any obvious clinical changes. However, these patients have subtle changes in personality, which may be reported by caregivers[10]. So, it is important for doctors to realize that HE may not have obvious clinical symptoms such as coma or convulsions, which are very rarely reported in HE but may be as mild as behavioral changes.

Regarding examination, assessment of conscious level, general look, and vital signs was fulfilled well, but fetor hepaticus was not recorded in 57.7% of cases, and this may be owing to resident doctors who are more concerned with diagnosis, grading, and management of HE. The presence of fetor hepaticus is not constant; patients with cirrhosis without HE can have this condition[11].

Data about general and systemic examination (abdominal examination, chest and cardiac examination, and upper and lower limb examination) were fulfilled in 100% of cases except flapping tremors of the hand (asterixis) which was evaluated in 36.5% of cases because assessment of this sign needs cooperative patients, which is not accessible in very young and comatosed children. The recent International Society for Hepatic Encephalopathy and Nitrogen Metabolism consensus uses the onset of disorientation or asterixis as the onset of overt HE[12]. However, asterixis is not pathognomonic of HE because it can be observed in other diseases (e.g. uremia)[10]. Neurological examination was recorded in 91.2% of cases; there was hyperreflexia and hypertonia in 27% of cases, hyporeflexia and hypotonia in 31% of cases, areflexia in 23.1% of cases, and normal reflexes and normal muscle tone in 18.9% of cases. It is important to inform the doctors about the importance of neurological examination in children with HE. Regarding investigations, most recommended investigations were done for all patients except urine analysis, which was done in only 71.2% of cases, and it is recommended to be done in all cases later on. Electrophysiological evaluation of HE is not routine. The EEG may be abnormal in subclinical HE and early stages of HE. It is usually abnormal in late stages of HE[13]. So, EEG has no diagnostic value in HE, and in this study, EEG was performed in six cases which were the cases that had convulsion, and we recommend this to prevent abuse of investigations especially in countries with limited resources like ours. Serum ammonia level was not done in any case as it is not available in Assiut University Children Hospital, and this will cost the parents and does not add any diagnostic, staging, or prognostic value in HE. This opinion is in accordance to Lockwood[14], who stated that high blood-ammonia levels alone do not add any diagnostic, staging, or prognostic value in HE in patients with chronic liver disease.

Regarding treatment, the international guidelines for the management of HE have been followed by the Gastroenterology and Hepatology Unit of Assiut University Children Hospital in most treatment lines except admission to the ICU, as no case of grade 3 or 4 HE was admitted to ICU (instead they all were admitted at Gastroenterology Intermediate Care Unit). Therefore, prophylactic endotracheal intubation was not applicable.

Previous authors reported that comatosed patients should be admitted to intensive care and endotracheal intubation considered if their airway is compromised[15]. However, this was not applied in this study, and this may be owing to lack of places in ICU because it has limited number of beds that are allocated for patients requiring mechanical ventilation only. Insertion of nasogastric tube was done in 100% of cases. Enemas, empirical antibiotics, lactulose, neomycin, and L-ornithine L-aspartate (Hepamerz) were given in 100% of cases. Management of precipitating factors of HE was done in 100% of indicated cases. In this study, intravenous branched-chain amino acids were given in 7.7% of cases who need total parenteral nutrition (TPN), but oral branched chain amino acids (BCAAs) were not used at Gastroenterology and Hepatology Unit because they are not available. Unfortunately, infusion of BCAAs was reported to increase venous blood ammonia in most patients with liver failure[16]. So, it is important to have hospital-based formula in Assiut University Children Hospital for different disease management especially oral formulas enriched with BCAA, which is very important for children with chronic liver disease. Zinc administration has the potential to improve hyperammonemia by increasing the activity of ornithine transcarbamylase, an enzyme in the urea cycle[17]. In the present study, zinc was given in 17.3% of cases, and some cases show slight improvement in the physical component. So, it is recommended to use zinc in all children with HE later on. Rifaximin was not used in the present study. Instead another nonabsorbable antibiotic (Neomycin) was used in all cases. Some oral antibiotics such as neomycin are not recommended for long-term use because of nephrotoxicity, ototoxicity, and peripheral neuropathy and are specifically contraindicated in patients with liver disease[18]. Rifaximin added to lactulose is the best-documented agent to maintain remission in patients who have already experienced one or more bouts of HE while on lactulose treatment after their initial episode of HE[19]. So, it is recommended to be subscribed in children with recurrent HE for prevention of HE recurrence as long-term therapy.

 Conclusion



The international guidelines for the management of HE have been followed by the Gastroenterology and Hepatology Unit of Assiut University Children Hospital in most treatment lines and that some of the default is owing to poor-resource setting and lack of medication.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

References

1Suchy FJ. Fulminant hepatic failure. Nelson textbook of pediatrics. 17th ed. Pennsylvania, USA: Saunders; 2004. 134–213.
2Butterworth RF. Neurosteroids in hepatic encephalopathy: novel insights and new therapeutic opportunities. J Steroid Biochem Mol Biol 2016; 160:94–97.
3Shawcross DL, Dunk AA, Jalan R. How to diagnose and manage hepatic encephalopathy: a consensus statement on roles and responsibilities beyond the liver specialist. Eur J Gastroenterol Hepatol 2016; 28:146–152.
4Riggio O, Efrati C, Catalano C. High prevalence of spontaneous portal-systemic shunts in persistent hepatic encephalopathy. Hepatology 2005; 42:1158–1165.
5Poordad FF. The burden of hepatic encephalopathy. Aliment Pharmacol Ther 2007; 25 (Suppl 1):3–9.
6Strauss E, Tramote R, Silva EP, Caly WR, Honain NZ, Maffei RA. Double-blind randomized clinical trial comparing neomycin and placebo in the treatment of exogenous hepatic encephalopathy. Hepatogastroenterology 2002; 39:542–545.
7Arya R, Gulati S, Deopujari S. Management of hepatic encephalopathy in children. Postgrad Med J 2010; 86:34–41.
8Rockey DC, Seeff LB, Rochon J, Freston J, Chalasani N, Bonacini M. Causality assessment in drug-induced liver injury using a structured expert opinion process: comparison to the roussel-uclaf causality assessment method. Hepatology 2010; 51:2117–2126.
9Keeffe EB, Friedman LM. Handbook of liver diseases. Edinburgh: Churchill Livingstone; 2004. 104–123.
10Weissenborn K, Bokemeyer M, Krause J, Ennen J, Ahl B. Neurological and neuropsychiatric syndromes associated with liver disease. AIDS 2005; 19 (Suppl 3):S93–S98.
11Nolte W, Wiltfang J, Schindler CG. Bright basal ganglia in T1-weighted magnetic resonance images are frequent in patients with portal vein thrombosis without liver cirrhosis and not suggestive of hepatic encephalopathy. J Hepatol 2000; 29:443–449.
12Bajaj JS, Saeian K, Schubert CM. Minimal hepatic encephalopathy is associated with motor vehicle crashes: the reality beyond the driving test. Hepatology 2009; 50:1175–1183.
13Pappas SC, Jones EA. Methods of assessing hepatic encephalopathy. Semin Liver Dis 2001; 3:298–307.
14Lockwood AH. Blood ammonia levels and hepatic encephalopathy. Metab Brain Dis 2004; 19:345–349.
15Blei AT, Cordoba J. Practice parameters Committee of the American College of Gastroenterology. Hepatic encephalopathy. Am J Gastroenterol 2001; 96:1968–1976.
16Nishikawa Y, Ukida M, Matsuo R, Morimoto Y, Omori N, Mikami M, Tsuji T. Administration of a branched chain amino acid preparation during hepatic failure: a study emphasizing amonia metabolism. Acta Med Okayama 1994;48:25-30.
17Chetri K, Choudhuri G. Role of trace elements in hepatic encephalopathy: zinc and manganese. Indian J Gastroenterol 2003; 22(Suppl 2):S28–S30.
18Hampel H, Bynum GD, Zamora E, El-Serag HB. Risk factors for the development of renal dysfunction in hospitalized patients with cirrhosis. Am J Gastroenterol 2001; 96:2206–2210.
19Bass NM, Mullen KD, Sanyal A, Poordad F, Neff G, Leevy CB. Rifaximin treatment in hepatic encephalopathy. N Engl J Med 2010; 362:1071–1081.