Laboratory Abnormalities In Hepatic Encephalopathy
An elevated blood ammonia level is the classic laboratory abnormality reported in patients with hepatic encephalopathy. This finding may aid in correctly diagnosing patients with cirrhosis who present with altered mental status. However, serial ammonia measurements are inferior to clinical assessment in gauging improvement or deterioration in a patient under therapy for hepatic encephalopathy. Checking the ammonia level in a patient with cirrhosis who does not have hepatic encephalopathy has no utility. Only arterial or free venous blood specimens must be assayed when checking the ammonia level. Blood drawn from an extremity to which a tourniquet has been applied may provide a falsely elevated ammonia level when analyzed.
Classic EEG changes associated with hepatic encephalopathy are high-amplitude low-frequency waves and triphasic waves. However, these findings are not specific for hepatic encephalopathy. When seizure activity must be ruled out, an EEG may be helpful in the initial workup of a patient with cirrhosis and altered mental status.
Visual evoked responses also demonstrate classic patterns associated with hepatic encephalopathy. However, this test is not in common clinical use.
Why Is Lactulose Used For Hepatic Encephalopathy
Hepatic encephalopathy is a medical condition that is characterized by mental disorders in patients with chronic liver diseases or portal hypertension. In hepatic encephalopathy there is buildup of toxins in the brain, which leads to neurological and psychological symptoms in patients suffering from this condition. This could be attributed to impaired liver function due to various causes such as cirrhosis, portal hypertension, liver failure, Reyes disease, infection, hypovolemia or dehydration, constipation, electrolyte imbalance due to diuretics causing hypokalemia or hyponatremia, sedatives such as barbiturates or benzodiazepines, nitrogen overload in the gut or renal failure.
The symptoms of hepatic encephalopathy range from mild to severe depending on the above underlying causes. These include sleep disturbance, confusion, forgetfulness, mood swings, memory problems, lethargy, slurred speech, deterioration of motor skills such as writing or driving, tremors, changes in personality and behavior, irritability, apathy, disorientation, stupor, drowsiness, coma and even death if underlying disease is not managed on time.
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What Should I Know About Storage And Disposal Of This Medication
Keep this medication in the container it came in, tightly closed, and out of reach of children. Store it at room temperature and away from excess heat and moisture .
Unneeded medications should be disposed of in special ways to ensure that pets, children, and other people cannot consume them. However, you should not flush this medication down the toilet. Instead, the best way to dispose of your medication is through a medicine take-back program. Talk to your pharmacist or contact your local garbage/recycling department to learn about take-back programs in your community. See the FDA’s Safe Disposal of Medicines website for more information if you do not have access to a take-back program.
It is important to keep all medication out of sight and reach of children as many containers are not child-resistant and young children can open them easily. To protect young children from poisoning, always lock safety caps and immediately place the medication in a safe location â one that is up and away and out of their sight and reach.
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Neuropsychological Test In Mhe
Neuropsychological testing is useful methodology for quantifying cognitive impairment due to various forms of encephalopathy, including low-grade or MHE. Neuropsychological tests directly measure cognitive functions that are directly relevant to activities of daily living. They have been applied for the diagnosis of HE for more than 50 years.
The neuropsychological features of MHE point to a disorder of executive functioning, particularly selective attention, visuospatial abilities and fine motor skills. Although these domains are most commonly implicated in MHE, impairments of memory have also been reported.
The attention impairments in MHE are observed on a variety of measures. These include measures of cognitive processing speed involving psychomotor responding, such as the Number Connection tests , block design test ,the Digit Symbol test , line drawing test, circle-dotting test, serial-dotting test, figure connection test. Impairments on measures of cognitive processing speed and response inhibition that do not require a motor response have also been reported . Visuospatial impairments have been primarily reported on block design tasks , but also on more pure measures of visuospatial perception, such as line orientation or the Hooper test. Fine motor skill impairments have been noted on measures such as the grooved pegboard task, and on line tracing tasks .
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Consumer Information Use And Disclaimer
- If your symptoms or health problems do not get better or if they become worse, call your doctor.
- Do not share your drugs with others and do not take anyone else’s drugs.
- Some drugs may have another patient information leaflet. Check with your pharmacist. If you have any questions about lactulose solution , please talk with your doctor, nurse, pharmacist, or other health care provider.
- If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.
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Assessment Of The Need For Long
Patients with cirrhosis are at risk of developing new episodes of encephalopathy. Several factors need to be considered:
Diet and Nutrition
Low-protein diets are often erroneously recommended for patients with cirrhosis, in hopes of decreasing intestinal ammonia production and of preventing exacerbations of HE. An obvious consequence was the worsening of preexisting protein-energy malnutrition. Protein restriction may be appropriate in some patients immediately following a severe flare of symptoms . However, protein restriction is rarely justified in patients with cirrhosis and persistent HE. Indeed, malnutrition is a more serious clinical problem than HE for many of these patients.
It is the infrequent patient who is intolerant of a diet high in protein. Most patients with mild chronic HE tolerate more than 60 to 80 g of protein per day.
Diets containing vegetable proteins appear to be better tolerated than diets rich in animal protein. This may be because of increased content of dietary fiber, a natural cathartic, and decreased levels of AAA. AAA, as precursors for the false neurotransmitters tyramine and octopamine, are thought to inhibit dopaminergic neurotransmission and worsen HE. Ingestion of red meat protein should be discouraged.
Control of Potential Precipitating Factors
Higher Likelihood of Recurrent Encephalopathy
Assessment of the Need for Liver Transplantation
Hepatic Encephalopathy and Fitness to Drive
Reduction Of Nitrogenous Load From The Gut
Lactulose and lactilol are nonabsorbable disaccharides in common clinical use since the early 1970s . They are degraded by intestinal bacteria to lactic acid and other organic acids.
Lactulose appears to inhibit intestinal ammonia production by a number of mechanisms. Colonic metabolism of lactulose to lactic acid results in acidification of the gut lumen. This favors conversion of ammonium to ammonia and the passage of ammonia from tissues into the lumen. Gut acidification inhibits ammoniagenic coliform bacteria, leading to increased levels of nonammoniagenic lactobacilli. Lactulose also works as a cathartic, reducing colonic bacterial load.
Initial lactulose dosing is 30 to 40 mL orally, daily or twice daily. The dose may be increased as tolerated. Patients should be instructed to reduce lactulose dosing in the event of diarrhea, abdominal cramping, or bloating. Patients should take sufficient lactulose as to have two to four loose stools per day.
Care must be taken when prescribing lactulose. Overdosage can result in ileus, severe diarrhea, electrolyte disturbances, and hypovolemia. Hypovolemia may be sufficiently severe as to actually induce a flare of encephalopathy symptoms.
Table 2: Summary of the Antibiotic Regimens Commonly Used for Hepatic Encephalopathy
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How To Administer Lactulose
If this medication is to be taken orally then it should be used three to four times daily or as instructed by a doctor. The taste can be improved by mixing it with water, fruit juice, soft dessert, or milk. The main goal here is that the patient has two to three daily soft stools. However, the dosage to be taken will depend on how responsive the patient has been and their medical condition.
When taken rectally, the recommended dosage should be mixed in normal saline or water. Apply the solution and allow the liquid to stay in the rectum for the next thirty to sixty minutes or as instructed by the doctor. If the medication is kept below thirty minutes then it should be repeated unless told otherwise.
This medication should be used regularly for optimum benefit and effect. Remember that is is to be used at the same time daily. Rectal administration of lactulose can improve mental status for like two hours. But oral administration may require up to twenty-four to forty-eight hours.
How Is This Medicine Best Taken
Use lactulose solution as ordered by your doctor. Read all information given to you. Follow all instructions closely.
- Do not take antacids at the same time as lactulose solution . Talk with your doctor.
- Measure liquid doses carefully. Use the measuring device that comes with lactulose solution . If there is none, ask the pharmacist for a device to measure lactulose solution .
- Mix liquid with water, milk, or fruit juice to make it taste better.
- Some products may be used as an enema. If you are using lactulose solution as an enema, it will be given rectally by your doctor.
What do I do if I miss a dose?
- If you take lactulose solution on a regular basis, take a missed dose as soon as you think about it.
- If it is close to the time for your next dose, skip the missed dose and go back to your normal time.
- Do not take 2 doses at the same time or extra doses.
- Many times lactulose solution is taken on an as needed basis. Do not take more often than told by the doctor.
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Pathophysiology Of Hepatic Encephalopathy
HE is thought to be primarily because of ammonia-induced neurotoxicity and excessive GABAnergic inhibitory neurotransmitter activity. Ammonia produced either by catabolism of nitrogenous sources or by glutamine metabolism at a mitochondrial level, has been shown to lead to astrocyte swelling and dysfunction . Metabolism of glutamine into ammonia and glutamate may additionally cause stimulation of N-methyl-D-aspartate receptor receptors triggering nitric oxide release and subsequent vasodilation. This vasodilation may lead to hyperemia and cerebral edema . In addition, cerebral autoregulation has been found to be impaired in patients with acute hepatic failure . A variety of other mechanisms may be involved in the pathogenesis of HE including catecholamine and other neurotransmitter abnormalities, and activation of the aquaporin-4 water channel protein on astrocytes. Inflammation may also play a role because elevated TNFa levels have been documented in patients with elevated ICP compared with those without .
Provision Of Supportive Care
Standard supportive care is required for all hospitalized patients with HE. Patient safety and frequent bedside monitoring of mental status are crucial. This can require additional personnel and, in the case of comatose patients, admission to the intensive care unit, endotracheal intubation, or both. Although temporary restriction of dietary protein may be necessary, patients with HE should avoid prolonged periods of fasting. Although the restriction of dietary protein at the time of acute HE can be part of therapy, protracted nitrogen restriction can lead to malnutrition. Appropriate enteral nutrition, by mouth or nasogastric feeding tube, should be administered as soon as feasible.
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What Are The Side Effects Of Lactulose
Quite a few adverse effects may occur when you use lactulose. They include bloating, gas, stomach rumbling, burping, stomach pain, cramps, and nausea. If you experience any one of these, you should notify your physician or pharmacist.
Sometimes, you may be afraid of adverse effects even before you use the drug. But remember, your doctor knows about these adverse effects. Yet, he prescribed it for you because he believes that its benefits far outweigh the risks or side effects.
In truth, most people that use lactulose have no serious adverse effects whatsoever. But then, some unlikely but severe effects require urgent attention. You should let your doctor know right away in case you experience any of them. They include:
There are also serious allergic reactions, but they are quite unlikely. But you must seek immediate expert care if ever it occurs. Some allergic reactions that may occur include:
- Trouble breathing
- Severe dizziness
The list above is not exhaustive. So you may notice some other effects that are not on the list. If you experience any strange effects, you should contact your pharmacist or physician or pharmacist.
One precaution you must bear in mind is to let your healthcare provider know before you use lactulose. Also, inform him or her about any allergies you may have had in the past. The medication may contain some inactive ingredients that may cause allergies.
- Lactose intolerance
- History of diabetes
Comparison Of Treatment Groups
The 2 groups were similar with respect to demographics and clinical features . The precipitants of HE included a total of 80 potential contributing factors identified in 50 patients . Admission laboratory data were also similar in the 2 groups , with the exception of blood urea nitrogen level, which was higher in the PEG group . Admission ammonia levels were elevated in both groups . Nineteen patients in the lactulose group and 18 patients in the PEG group underwent head computed tomography scanning. No acute CT findings were identified in any patient.
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What Dose Of Lactulose Should I Take For He
Lactulose dosage can vary, so ask your doctor about the best dose for you2. It is important not to overdose on lactulose, as you could end up experiencing severe diarrhea, which can lead to a dangerous loss of fluids and electrolytes. Overdose can also slow down the movement of your intestines the opposite effect of what you want in HE, so make sure you follow the advice of your healthcare team.1
Lactulose is a type of sugar that is commonly used as a treatment for constipation as well as for HE.
Is It Time To Rethink Lactulose For The Treatment Of Acute Hepatic Encephalopathy
Jennifer Best, MD, FACP, FHM
Associate Professor, University of Washington School of Medicine, Seattle, WA
Dr. Best reports no financial relationships in this field of study
For decades, lactulose, a non-absorbable disaccharide, has been considered to be the standard-of-care, first-line therapy for acute hepatic encephalopathy. Hepatic encephalopathy , a complication of decompensated liver cirrhosis, represents a spectrum of clinical manifestations ranging from mild neuropsychiatric changes to coma and is a common indication for hospital admission. The pathogenesis of this condition is not entirely well understood, though certain entities, such as ammonia and its interaction with the bacterial flora of the gut, are known to be important. Prior to the use of non-absorbable disaccharides, laxatives represented a primary mode of therapy with the goal of gut lavage and more rapid transit, preventing bacterial metabolism of ammonia. Though evidence now supports the use of rifaximin for recurrent HE, this agent does not represent an advance in first-line therapy. Furthermore, the effectiveness of bowel catharsis with laxatives, such as polyethylene glycol has not been evaluated in comparison with non-absorbable disaccharides.
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Precautions When Using This Drug
It should not be given to patients with intestinal obstruction
It should not be used in patients on a low galactose diet and care should be taken in patients with lactose intolerance or in diabetic patients because of the presence of some free galactose and lactose sugars.
Severe lactic acidosis developed in a patient with adynamic ileus who was being given lactulose of hepatic encephalopathy.
Side Effects Of Lactulose
Bloating, gas, nausea, stomach pain, cramps, and burping may happen. If they persist or gradually worsen please notify a pharmacist or doctor immediately.
Remember that the doctor prescribed this drug after weighing the pros and cons and judged that there are higher chances of a benefit than developing side effects. The majority of the people who used this lactulose medication do not experience its side effect so the chances are slim.
However, if you notice any of the following severe side effects seek urgent medical attention. The symptoms are vomiting, diarrhea, seizures, irregular heartbeat, muscle weakness and cramps, and mood changes.
Developing severe allergy is highly unlikely but if it does happen then run to a doctor. The symptoms of a severe allergic reaction are itching/swelling, severe dizziness, rash, difficulty in breathing.
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Oxidative And Nitrosative Stress
Enhanced production of reactive nitrogen species and reactive oxygen species occurs in cultured astrocytes that are exposed to ammonia, inflammatory cytokines, hyponatremia or benzodiazepines. It’s suggested that glutamine formed in the cytoplasm enters the mitochondrial matrix and is cleaved to release ammonia while still inside the mitochondria. Evidence indicating a close association and interplay between astrocyte swelling and ROS is now growing.
What Is Lactulose And How Does It Work
Lactulose is a prescription drug used by mouth or rectally to treat or prevent complications of liver disease . It does not cure the problem, but may help to improve mental status. Lactulose is a colonic acidifier that works by decreasing the amount of ammonia in the blood. It is a man-made sugar solution.
- Lactulose is available under the following different brand names: Enulose, Kristalose, Constulose, and Generlac.
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High Blood Ammonia Levels In Liver Cirrhosis
Ammonia is a substance that is made in our bodies as a by-product of various metabolic processes. Ammonia is toxic to your nervous system at high levels, but the levels of it in your blood are normally kept under control by your liver, which stops ammonia from entering your circulation by converting it into other substances. Your muscles are also able to remove ammonia from the blood.1
In advanced liver disease, dysfunction of the liver and wasting of the muscles means that both of these important ammonia-clearing processes are impaired. Ammonia levels start to build up in the blood and contribute to the development of HE.1
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