CHAPTER I

PRELIMINARY

1.1. Background
Encephalopathy is a disorder of cerebral function in general that can be acute or chronic,
prolonged or static. Etiology of encephalopathy in children can be caused by infection,
poisoning (eg carbon monoxide, drugs, lead), metabolic, and ischemic causes such as
ischemic hypoxic. The likelihood of etiology is partially determined by the age of the child.
Hypoglycemia, excess medications, and toxins are things that should be considered in young
children, while neurologic complications in viral diseases are likely in the older child.1
The major clinical sign of encephalopathy is a disorder of consciousness that ranges from
mild confusion to deep coma. neurologic disorders are more generalized (diffuse) than focal.
Seizures, if they arise, may be general or focal. Neurologic findings are usually bilaterally
symmetrical and include changes in muscle tone and reflex activity as well as the presence of
a sign of babinski. 1
Children with encephalopathy may also regress in general cognitive function, academic
achievement, neuropsychological function and habits. The intelligence score of patients with
encephalopathy is also low when compared to children of his age. From an academic
perspective, patients often have difficulty reading, spelling and arithmetic. As for
neuropsychological function, patients can become hyperactive or autistic.

2.1. Definition
Encephalopathy is a term used to describe a disorder of general brain function that can be
acute or chronic, progressive or static. Encephalopathy is a general cortical dysfunction that
has acute travel characteristics up to subacute (hours to days), significantly fluctuations of the
level of consciousness, minimal attention, frequent hallucinations and delusions and changes
in psychomotor activity levels (generally increases, but may decrease) . The use of the term
encephalopathy describes a general change in brain function, which manifests in attention
disorder, either in the form of hyperalert agitation to coma.1

2.2. Epidemiology
The incidence of encephalopathy has not been widely studied, the study was conducted on
each type of encephalopathy. Research conducted in London, showed that the incidence of
hypoxiciskemic encephalopathy reached 150 per 57 thousand live births or ranged 2.64%.
While research conducted in East Australia showed a higher figure of 164 per 43 thousand
live births or around 3.8%. It is estimated that about 30% of cases of hypoxic encephalopathy
in developed countries and up to 60% in developing countries are associated with intrapartum
ischemic hypoxic events.3

2.3. Etiology
Encephalopathy is a disorder of the brain that has many causes including infectious agents,
toxic (eg carbon monoxide, drugs, lead, metabolic and ischemic). 1 These various etiologies
are commonly used for encephalopathy classification.

2.4 Classification
2.4.1 Infection-related Encephalopathy
a. Definition
Encephalopathy is the commonest manifestation of sepsis and septic patients with
encephalopathy have a higher mortality rate than without encephalopathy. Some findings
suggest that encephalopathy may be the cause of death of septic patients. Encephalitis and
encephalopathy should be indistinguishable, where in the encephalopathy there is impaired
brain function without direct inflammatory process in the brain parenchyma. The neonate
does not always give prominent large crown symptoms. Patients may exhibit symptoms of
global encephalopathy such as coma or epileptic status. Early diagnosis and treatment with
appropriate antibiotics or antivirals is important.4
Encephalopathy caused by systemic infection is the most difficult to distinguish from
encephalitis. The identifiable differences between encephalopathy and encephalitis can
generally be seen in the following table.
 Ensefalopati Ensefalitis
clinical
manifestations
fever - +
Headache - +
Depression Deterioration Maybe fluctuations
mental status
Focal - +
neurological
signs
Type of General General or focal
seizures
Laboratory
Findings
Blood Leukositosis (-) Leukositosis

LCS Pleositosis (-) Pleositosis

EEG Edema Focal swelling and abnormalities

MRI Sometimes normal Focal abnormalities

Dysfunctional or multifocal cerebral dysfunction induced by systemic responses to infections

with no clinical evidence or laboratory direct brain infections is called septal
encephalopathy.6,7

b. Pathogenesis

The pathogenesis of sepsis encephalopathy remains unclear. Some possibilities are suggested
as a cause of brain damage during severe sepsis, the effects of endotoxin and inflammatory
mediators, blood brain barrier dysfunction and cerebrospinal fluid damage, amino acid and
neurotransmitter changes, apoptosis, oxidative stress and excitotoxicity, but the most trusted
hypothesis is multifactorial.6

Endotoxin. Bacterial toxin and its particles, lipopolysaccharide, is one of the causes of brain
dysfunction during sepsis. Lipopolysaccharides in sepsis state will increase and will react
directly with the brain in circular organs that are not protected by the blood-brain barrier.
Lipopolysaccharides may bind to receptors such as toll-like receptors, inducing the synthesis
of inflammatory cytokines, prostaglandins and nitric oxide (NO) from microglia and
astrocytes. At low concentrations, endotoxins can induce the secretion of inflammatory
cytokines, IL-6 from monocytes / macrophages, which will react directly by inducing the
expression of inflammatory mediators.6

Inflammatory mediator. When infection occurs, peripheral macrophages / monocytes secrete

inflammatory cytokines including, IL-1, TNF-α, and IL-6, which play an important role in
mediating the cerebral responses in the infection. These three mediators can induce
cyclooxygenase 2 (COX2) from glia cells and synthesize prostaglandin E2 responsible for
activation of the hypothalamus-pituitary-adrenal axis, fever and habitual changes. The
activation of the complement cascade, including anaphylactoxin C5a, is also associated with
brain dysfunction during sepsis, possibly by initiating damage to the blood-brain barrier.6

Blood Damage Dysfunction of the brain. Both lipopolysaccharides and cytokines can induce
endothelial activation called panendothelitis. They will induce the expression of adhesion
molecules in the brain's microvascular endothelial cells, they also induce the secretion of
proinflammatory cytokines and nitric oxide syntase (NOS). Endothelial activation results in
increased permeability and damage to blood brain barrier with further consequences will
form vasogenic brain edema. Astrocyte feet around the cortical blood vessels will become
swollen and membrane rupture will occur and release the blood vessel wall. An astrocytic
foot swelling is a direct consequence of blood brain damages. Brain edema that occurs in
sepsis encephalopathy is more associated with loss of autoregulation compared to blood brain
damages even if early vasogenic edema may become cytotoxic edema.6

Brain blood flow and cerebrospinal autoregulation. Brain blood flow decreases and brain
ischemia may be caused by brain damage during severe sepsis. Damage to cerebral blood
flow is also a result of microvascular damage, which occurs in other organs, not because of
the effect of systemic hypotension.6
Mitochondrial dysfunction. Mitochondrial dysfunction is associated with neuron cell
apoptosis and inadequate energy supply. The decrease in ATP produced by mitochondria is
caused by cytokines, reactive oxygen species (ROS) and NO. Mitochondria may also induce
apoptosis by secreting C. cytochrome 6

c. Clinical Symptoms

Sepsis encephalopathy generally occurs early in severe sepsis and causes multiorgan failure.
The most common clinical state of affairs is a decrease in the level of consciousness from
mild to unresponsive consciousness and coma. Fluctuating confucional status,
inappropriateness and inappropriate habits also occasionally occur in patients with mild
encephalopathy. In more severe cases it can lead to delirium, agitation and deterioration of
consciousness and coma. Motor symptoms are rare in septic encephalopathy, and many occur
in metabolic encephalopathy, such as asterixis, myoclonus and tremor. In encephalopathy
sepsis that may arise is a form of parathonic rigidity, a resistance that depends on the speed to
passive movement. Seizures may also arise in septic encephalopathy, but are not common,
cranial nerve dysfunction and lateralisation are rare and should be able to exclude other
possible causes. 6

d. Diagnosis

The diagnosis of septic encephalopathy is clinically dependent on the exclusion of other

possible causes of brain deterioration (metabolically or structurally). EEG is one of the most
sensitive investigations and may exhibit abnormalities despite normal neurologic
examination. EEG patterns that can be found in encephalopathy sepsis are normal EEG,
excessive theta, predominant delta, triphasic wave, suppression. EEG examination of septic
encephalopathy is not specific, because it can also be found in the influence of sedation and
metabolic damage. CT Scan head not found abnormalities, but examination to rule out the
existence of brain damage caused by hypoxic / ischemic. The development is the use of
biomarkers to detect septic encephalopathy, ie S100B and NSE. S100B is a protein bound by
calcium produced by the central nervous system, mainly by the astroglial cells. S100B will
increase in serum and cerebrospinal fluid after brain injury. NSE is an enolase enzymatic
intrasitoplasmic glycolytic enzyme, which can be found in nerve cells and neuroendocrine
tissue and increases in blood circulation after increased nerve cell death.6

e. Management
Treatment of septic encephalopathy in particular still does not exist, treatment is done with
sepsis treatment.6

Supportive therapy is required such as maintaining a warm environment, giving symptomatic

treatment such as vomiting, anemia and fever. Then performed antibiotics for approximately
14 days.6

2.4.2 Ischemic Ischemic Encephalopathy

a. Definition

Hypoxic Ischaemic Encephalopathy (HIE) is a term commonly used to describe the clinical
syndrome as a result of perinatal asphyxia, resulting in lack of perfusion and oxygen to the
brain. This causes permanent CNS damage that may result in neonatal death or in later stages
leading to cerebral palsy or mental deficits. 8

b. Epidemiology

In the US, perinatal asphyxia occurs from 1.0 to 1.5% of live births. Incidence decreases with
increasing gestational age and birth weight. The incidence of ischemic hypoxic
encephalopathy in the United States occurs in 2-9 per 1000 live births. The incidence rate in
developing countries per 1,000 live births, Malysia 18, Kuwait 18, India 59, Nigeria 265, at
RS. Dr. Soetomo Surabaya 12.25% of the 3405 babies treated in 2004 suffered from
asphyxia. His death rate is high around 50% of disability numbers related to the severity of
his illness. The assumption that the predominant cause of CP due to perinatal asphyxia is
incorrect, only 8.2% of CP cases are proved by perinatal asphyxia.9

c. Etiopathogenesis

Various causes that can cause perinatal asphyxia include: oxygenation disorders in pregnant
women, decreased blood flow from mother to placenta or from placenta to fetus, impaired gas
exchange through placenta or fetus, and increased fetal oxygen demand. Risk factors that can
cause perinatal asphyxia are maternal factor, placenta-umbilical cord, and fetus / neonates.

1) Maternal disorders: hypertension, vascular disease, diabetes, drug abuse, heart disease,
lung, and central nervous system, hypotension, infection, uterine rupture, uteri tetani, narrow
pelvis.
2) Placental and cord abnormalities: placental infarction and fibrosis, placental abruption,
prolapse or umbilical cord compression, umbilical vein abnormalities

3) Fetal / neonatal abnormalities: anemia, bleeding, hydrops, infection, impaired fetal growth,
serotonus.9

The combination of reduced oxygen supply to the brain that causes hypoxia and the lack or
absence of blood flow causing ischemia can lead to reduced glucose for metabolism and
lactate accumulation resulting in acidosis in local tissues. After reperfusion, ischemic hypoxia
can also cause cell necrosis complications and vascular endothelial edema, decreasing blood
vessel blood flow distal.9

d. Clinical Symptoms

Typically, ischemic ischemic encephalopathy in neonates has characteristics of cerebral

edema, cortical necrosis, and basal ganglia involvement, whereas in preterm neonates, it has
periventricular characteristics of leukomalacia. Both lesions can cause cortical atrophy,
mental retardation and quadriplegi or diplegi spastica.9

After birth, a combination of chronic fetal hypoxia and ischemic hypoxic injury results in
specific neuropathology according to gestational age. A term infant shows cortical neuron
necrosis (later atrophy of the cortex) and injury of parasagital ischemia. Preterm infants
demonstrate LPV (later diplegia spastik), basal ganglia marmoratus status, and PIV. The term
infant, more often than preterm infants, exhibits local or multifocal cortical infarcts that
produce localized (focal) and hemiplegia (local) convulsions. Stimulation of amino acids can
play an important role in the pathogenesis of brain lesion asphyxia.9

Neonates with encephalopathy may be accompanied by low APGAR values during labor and
umbilical blood metabolic acidosis; within 24 hours of life, apnea and seizure symptoms and
EEG (electroencephalography) abnormalities may occur.7 The neurological deficit may be
learning disorders, mental retardation, and visual and hearing impairment.10

Clinical symptoms and characteristics of ischemic hypoxic encephalopathy vary greatly

depending on the severity of the injury. Pallor, cyanosis, apnea, slow heart rate and no
response to stimuli are some of the common signs of ischemic hypoxic encephalopathy. The
neonate with hypoxic ischemic encephalopathy of degree 3 is usually hypotonic, although
initially seen hypertonus and alertness are increased shortly after birth. As it develops
cerebral edema, decreased brain function, cortical depression causing coma, and brainstem
depression cause apneu. As cerebral edema develops, seizures begin 12-24 hours after birth.
Neonates also have no signs of spontaneous respiration, hypotonus, and decreased or absence

of tendon reflex.9

sign Scale 1 Scale 2 Scale 3

level of Hiperalert Letargik Stupor

consciousness

muscle tone Normal Hypotonus Flaksid

Tendon / Hyperactive Hyperactive -

clonal
reflexes

Reflect moro Strong Weak -

Pupil Midriasis Miosis Anisokor, minimal

light reflect

seizures - + Desereberation

EEG Normal Low voltage Much suppression to

changes to isoelectric
seizure activity

duration <24 hours if 24 hours -14 days day to week

any other
progress may
remain normal
i. Management

The management principle of a newborn who has hypoxic-ischemic injury and is at risk of
secondary injury is

1. Early identification of infants at high risk Signs that may be acquired is an abnormal fetal
heart rate, infant depression (low Apgar score and prolonged), necessary resuscitation
(intubation, chest compression, administration of epinephrine), severe acidosis (umbilical pH
<7.0 with or base deficit ≥16 mEq / L), followed by abnormal early neurologic examination
results or abnormal EEG results.

2. Supportive care intensive To facilitate brain perfusion and adequate nutrition, necessary
supportive care such as correction hemodynamically disorders (hypotension, metabolic
acidosis), adequate ventilation, correction of metabolic disorders such as glucose, calcium,
magnesium, and other electrolyte, handling seizures, as well as monitor the failure of other
organs. One of the main factors of intensive care is to maintain adequate ventilation and
perfusion. Lack of oxygen will cause disruption of cerebrovascular autoregulation with the
consequent increase in brain cell injury. While severe hyperoxia early in life will lead to
increased oxidative stress that ultimately exacerbates long-term neurological status.

3. Consideration of interventions to improve the ongoing brain injury process.

Neuroprotective therapeutic interventions can be sorted into pharmacological and non-
pharmacological interventions. Although many neuroprotective therapies have been studied,
no neuroprotective agent has been safe and effective in treating neurologic sequelae after the
incidence of HIE in neonates. The goal of neuroprotective therapy is to reduce cerebral
damage by reducing the formation of toxic free radicals, inhibiting excessive calcium entry
into neurons, and reducing cerebral edema.

Non-pharmacological Interventions

1. Hypothermia Therapy Hypothermia therapy is currently the main therapy of HIE and
has been shown to be very effective in reducing the risk of death and infant disability
newborn gestational age ≥36 weeks with moderate and severe HIE classification.
However, neurologic deficits persist in 40-50% of patients after hypothermia therapy.
The main purpose of hypothermic therapy is to reduce brain metabolism, store energy,
and prevent secondary energy failure and cell death, so that no secondary injury phase
occurs. Temperature down to a temperature of 34.5 ± 0.5 ° C for selective head
 cooling and 33.5 ± 0,5 ° C for whole-body cooling has become the standard of
handling infants with brain injury. For each 1 ° core temperature drop, the cerebral
metabolic rate fell by 6-7%. Two methods of hypothermia therapy, namely
wholebody cooling and selective head cooling; no method is considered superior. The
mortality of the two methods is not very different, but the morbidity is different; in
whole-body cooling there is an increased frequency of occurrence of
thrombocytopenia, coagulopathy, and / or cholestasis. While the incidence of seizures
and the use of anticonvulsant drugs was higher in the selective head cooling method.
Hypothermic therapy is performed based on the following factors: Birth weight ≥1800
gram, Blood gas analysis, History of acute perinatal events, APGAR score, Need for
resuscitation, Physical examination (seizures, level of consciousness, spontaneous
activity, posture, tone, primitive reflex, and autonomic nervous system parameters)

2. Stem Cell Therapy. In hypoxic-ischemic injury, cell damage results in necrosis and
apoptosis. Stem cell therapy aims to replace damaged cells as well as the effects of
tropical factor release and anti-apoptotic factors that have anti-inflammatory effects.
However, the best types and sources of the cells are still unknown, most researchers
using neural stem cells or mesenchymal stem cells. Some studies use umbilical cord
blood as a stem cell source because it is known to be rich in stem cells; the benefits
are easy to obtain, the primitive stem cells rich, do not require immunosuppressants
for autologous transplantation, and can be stored for up to ≥30 years. While the
disadvantage is the limited number of cells, potentially transmitting infections and
genetic diseases.
Pharmacological Interventions In general, the expected pharmacological effects are
the effects of antioxidants, anti-inflammatory, and antiapoptosis. Antioxidant effects
are expected to reduce toxic free radicals and inhibit the entry of excess calcium into
nerve cells. Allopurinol has an antioxidant effect and is known to reduce the
formation of free radicals that damage tissues and can keep the blood-brain barrier.
Human studies use 500 mg of intravenous allopurinol shortly before delivery to
infants suspected of fetal asphyxia. In recent years, cannabinoids are known to have
neuroprotective function because they can modulate neuronal and glial responses. In
addition, cannabinoids also have endothelial cell function, antiexitotoxic,
antiinflammatory, vasodilator effects, and regulate calcium homeostasis.10
Management of seizures in ischemic hypoxy encephalopathy is generally similar to
seizure management in neonatorum11:
1. Supervision of clean and open airway, oxygen delivery
2. Install IV lane and give liquid with maintenance dose
3. If the glucose level is less than 45mg / dL, treat hipoglikeminya before continuing
seizure management, to rule out the possibility of hypoglycemia as a cause of
seizures.
4. If the infant is in a seizure or a seizure infant in the last few hours, give a
phenobarbital injection of 20 mg / kg of body weight IV, given slowly within 5
minutes:
5. If IV is not yet installed, give a 20 mg / kg single dose of phenobarbital injection
IM, or the dose is increased by 10-15% compared to the IV dose.
• If the seizure does not stop within 30 minutes, repeat the phenobarbital 10 mg / kg
of body weight IV or IM. Can be repeated once more 30 minutes if necessary.
Maximum dose of 40mg / kgb / day.
• If the seizure persists or recurs, give a 20mg / kb injection of phenytoin by
considering the following:
• Phenytoin should only be given IV
If the seizure is resolved then proceed with anti-seizure administration, phenobarbital
5mg / kg / day is the first choice. Resistant cases should be treated with a combination
of phenobarbital and carbamazepine, although sodium valproate can be successful in
some cases 11.
The duration of maintenance dosage in the BBL seizure is still no agreement. Some
authors immediately discontinued maintenance doses after apparently no neurological
abnormalities, while others used a clinical picture benchmark and an EEG11 image.
Other anti-seizure medications such as diazepam are not recommended because they
can cause cardiorespiratoric instability when used in conjunction with phenobarbital,
and the main metabolite that has a long half-life, N-dismetyldiazepam, can cause
sedation without controlling the seizures. For this reason, diazepam is not the best
choice of benzodiepine for use on BBL.11
j. Prognosis
Patients who can live with stage 3 ischemic hypoxic encephalopathy have a high
incidence of seizures and experience serious disability especially in their neurological
development. The prognosis of severe asphyxia also depends on injury to other organ
systems.9
Another indicator of the ugly prognosis is the onset of spontaneous respiration that
can be estimated from the APGAR score. Neonates with APGAR score 3 in the 10th
minute had 20% mortality and 5% of cerebral palsy incidence. If up to the 20th
minute, APGAR score still does not rise even down, then the mortality rate increased
to 60% and the incidence of cerebral palsy increased to 57% .9

2.4.3 Metabolic Encephalopathy

a. Definition and Classification
Encephalopathy with metabolic problems as basically a problem for both neonates
and children, with functional outcomes dependent on time and careful intervention.
Metabolic encephalopathy is a general understanding of the clinical state
characterized by:
1) Decreased moderate to severe consciousness
2) Neuropsikoatrik disorders: seizures, lateralisation
3) Abnormalities of brain neurotransmitter function
4) With no signs of a clear bacterial infection.
Common metabolic disorders are hepatic dysfunction, renal dysfunction, and
metabolic disorders. The most common disorder is hepatic dysfunction, so the one
discussed in this referent is hepatic encephalopathy.
b. Pathophysiology
It should be emphasized that the pathophysiology of hepatic encephalopathy in
children is very different from that in adults where there is always chronic liver
disease and cirrhosis. In children, hepatic damage occurs acutely. The causes of
hepatic encephalopathy in children vary from viral hepatitis, to the destruction of
metabolism from birth, whereas in adults, alcohol-induced hepatic disease is more
common. In addition, in children with cerebral edema is an important complication
that can be found in the early stages.12
There are four theories of nerve damage to fulminant hepatitis, accumulation of
ammonia, brain neurotransmitter errors, abnormal ligand in γ amino butyric acid
benzodiazepine (GABA-BDZ) receptors, manganese deposits in basal ganglia.
Theory of Ammonia. Ammonia has long been recognized as a neurotoxin responsible
for the pathogenesis of hepatic encephalopathy. Ammonia is produced from several
tissues including the kidneys and muscles although the highest concentration is in the
portal vein derived from bacteria in the colon and the metabolism of glutamine in the
small intestine. In normal people, around 80-90% of ammonia is excreted through the
first metabolism. Excretion is reduced in both chronic and acute hepatitis. The
mechanism of hyperammonaemia causing encephalopathy remains unclear, studies
have shown that there is an increase in ammonia levels in hepatocyte cells that result
in changes in neurotransmitters, especially GABA agonists, leading to a failure to
provide energy for the brain. Detoxification of ammonia in astrocytes leads to the
accumulation of glutamine, which is a major cause of astrocytic swelling. In acute
hepatitis, glial swelling is also present when brain swelling occurs. Patients with
hepatic encephalopathy have more than 90% ammonia serum levels, and decreased
serum ammonia levels are associated with improved hepatic encephalopathy levels.
Experimental studies suggest that there is a strong correlation between glutamine
levels in cerebrospinal fluid with hepatic encephalopathy, but cognitive function
impairment such as episodic memory, the sustained attention occurring in hepatic
encephalopathy shows a correlation with serum ammonia levels when examined by
computer psychometric tests.12
The theory of neurotransmitter errors. Cerebral neurotransmitters are regulated by
amino acid concentrations and their precursors to the central nervous system. In
patients with severe hepatic dysfunction, plasma circulation concentrations of
aromatic amino acids (AAAs) of triptopan, tyrosine and phenylalanine are increased
while the concentration of double-chain amino acids (leucine, isoleucine and valine)
decreases, resulting in the production of faulty neurotransmitters (octopamide and
phenilethanolamide) which later developed into hepatic encephalopathy.12
GABA Theory. GABA is an inhibitory neurotransmitter in humans that works by
binding to the GABA receptor complex. An increased number of endogenous
benzodiazepines as neurosteroids results in inhibition of neurotransmission. Changes
in the GABA receptor complex and cerebral GABA concentration changes occur in
hepatic encephalopathy
Manganese Theory. Manganese accumulation in the ganglia, many in cirrhotic
patients and vice versa in hepatic transplant. Serum manganese concentrations
correlate with the degree of hepatic encephalopathy. Clinical manifestations of
manganese intoxication and extrapyramidal manifestations of hepatic encephalopathy
suggest that elevated manganese levels play a role in the occurrence of hepatic
encephalopathy.
c. Clinical Symptoms
The degree of mental status disorder in encephalopathy is classified according to the
West Haven criteria, ranging from sleep patterns disorder to cognitive function
changes and deep coma.

d. Management
The most common treatments in patients with hepatic encephalopathy are supportive
care, identification and treatment of accelerating factors, reducing intestinal nitrogen
products and identifying patients requiring long-term therapy.

1) Identify and eliminate precipitation factors ie infection.

Body fluid cultures can be a marker of infection. Patients with ascites should be
diagnostic parasentesis.
A child with hepatic encephalopathy should be treated in intensive care with a liver
transplant program, but limited resources. The first management is to include airway,
breating, and circulation, as well as handling other grave cases.12
2) Liquid management
After resuscitation, then what needs to be done next is the fluid balance. An important
goal to be achieved is normovolumik, because the presence of hydration of less or
more will interfere. Giving the fluid that is often done first is giving fluid about 70%
of maintenance. The hydration status should be monitored using central venous
pressure, targeting 6-8cm H2O. Urine monitoring is also needed to monitor hydration,
and renal function indicators. Intra venous administration of fluids as a medium of
administration of electrolytes and glucose in which encephalopathy is impaired.12
3) Potassium
Hypokalemi can be caused by the administration of diuretics, vomiting, and diarrhea.
Hypokalemi and its accompanying symptoms of alkalosis destroy the detoxification
of ammonia, increase the production of renal ammonia, increase the diffusion of
ammonia through the blood brain barrier. Potassium needs are estimated to range
from 3-6mEq / kgbb / d.12
Sodium
Total sodium intake of 1mEq / kgBW / day, usually adequate to prevent ascites. In
general, inappropriate secretion of the anti-diuretic hormone causes dilated
hyponatremia, which can be treated with fluid restriction. When free drainage is
required then it is usually given a diuretic combined with low salt albumin. The use of
hypertonic NaCl may be considered in cases with sodium levels of less than 120 mEq
/ l and / or falling rapidly.12
5) Glucose
Handling hypoglycemia is important for infants with hepatic encephalopathy.
Provision of minimal intravenous fluid containing 100mg / ml glucose (10%) and
infusion is done titration to maintain blood glucose between 120-240mg / dl. 11
6) ammonia restriction
Cleansing gastrointestinal mixture. Nasogastric tube installation is required to detect
and remove the presence of blood in the upper gastrointestinal tract, and provide
continuous drainage. This can prevent accelerated bleeding because of gastric
mucosal damage that may occur due to suction. Gastric washing is usually done with
50% magnesium sulfate solution, but it can be used enemas retention (20% lactose)
but is still rarely used due to availability and lack of research.
Antibiotics
Many antibiotics can be used in liver encephalopathy patients to "clear" the
gastrointestinal tract, including ampicillin, metronidazole, vancomycin, rifamixin. Of
these antibodies, rifaximin exhibits a broad spectrum of gram-positive and negative
and aerobic or anaerobic bacteria, in addition to rifaximin being absorbed at least
systemically. Helicobacter pylori (amoniogenic bacteria) can accelerate the
occurrence of liver encephalopathy in cirrhotic patients, especially in the presence of
gaster hypochloride. Therefore, antibiotics are also given to kill H. pylori.12
8) Protein
Restriction of protein or even total elimination is recommended until repair occurs. In
the last study, the administration of protein started from 0.5gram / kgBB / day with an
increase of up to 1.5gr / kgb / day, up to several weeks and hepatic repair. Provision
of vegetable protein is preferred over animal protein, as it is more tolerable and
contains less aminium, methionine and aromatic amino acids.
9) Lactose
Lactose is a disaccharide found in the caecum in an unmodified state, and then
converted by intestinal flora into components of glucose, galactose and fructose.
Galactose and lactose are metabolized into organic acids including lactic acid and
acetic acid, which causes the pH of the bowel lumen to drop to 5.5. This leads to the
prevention of the formation of easily absorbed ammonium ions
Probiotics
Theoretically, intestinal bacteria that do not produce urease will decrease the amount
of enteral ammonia. Research has been done with the provision of Lactobacillus
acidophilus per oral has a beneficial effect on cirrhotic patients who suffer from
hepatic encephalopathy. Lactobacillus acidophilus supplementation for 1-4 weeks
showed clinical clearance of 71% in patients with hepatic encephalopathy compared
with patients who received neomycin alone.12
11) Increased ammonia metabolism
Omithine-Aspartate. Infusion of 1omithine and 1-aspartate is an attempt to reduce
serum ammonia by increasing tissue metabolism against urea and glutamine. In
periportal hepatocytes, 1omithine acts as an ureagenesis substrate and activates the
enzyme cycle of urea omithine transcarbamylase and carbamoyl phospotase syntase.
The urea cycle activity is expected to consume ammonia and lower serum ammonia
levels. In hepatic perivena cells, where minimal urea cycle enzymes, aspartants (and
other decarboxylates) stimulate glutamine synthesis and initiate the ammonia
detoxification process. However, there is no basic dose for children, the
recommendation is still used up to 20 grams / day diluted in maintenance fluid.