Episode 46 - Hepatic Encephalopathy - a podcast by Rio Bravo Family Medicine Residency Program

Hepatic encephalopathy basics, disseminated gonococcal infections, polyarthralgia question winner, jokes.

Today is March 29, 2021.

On December 23, 2020, the California Department of Public Health (CDPH) sent a “Dear Colleague” letter because of the increasing reports of disseminated gonococcal infections (DGI). Today, we want to share with you parts of that letter. 

CDPH is working with local health departments to investigate these cases of DGI, where some patients have experienced homelessness or using illicit drugs, particularly methamphetamine. The CDC noted a similar increase in cases in Michigan in late 2019.

What is DGI? DGI is an uncommon but severe complication of untreated gonorrhea. DGI occurs when the sexually transmitted pathogen Neisseria gonorrhoeae invades the bloodstream and spreads to distant sites in the body, leading to clinical manifestations such as septic arthritis, polyarthralgia, tenosynovitis, petechial/pustular skin lesions, bacteremia, or, on rare occasions, endocarditis or meningitis. Patients have initially presented with joint pain attributed to another cause, which was only later determined to be due to DGI. 

Why is DGI increasing? Increased cases may be caused by decreased STD testing and treatment because of the COVID-19 pandemic, and not necessarily because of a more virulent strain of gonorrhea. 

What do we need to do as medical providers?

Screen: Reinstate routine screening recommendations for STDs in females <25 years of age (or older females with risk factors for STDs), pregnant females, men who have sex with men (MSM) and individuals with HIV, and other risk groups.

Suspect: For patients reporting joint pain, obtain a social history that includes a sexual and drug use history, and housing status. Suspect DGI in patients with joint pain and treat them according to the CDC STD Treatment Guidelines. Remember that most cases of uncomplicated gonococcal infections are now treated with a single dose of Ceftriaxone 500 mg IM PLUS doxycycline for 7 days. DGI, however, needs IV meds and longer duration of treatment.

Test: Order Nucleic acid amplification test (NAAT) and culture specimens from urogenital, extragenital mucosal sites (e.g., pharyngeal and rectal), and from disseminated sites (e.g., skin, synovial fluid, blood, and cerebrospinal fluid) before initiating empiric antimicrobial treatment for patients with suspected DGI. Hospitalization and consultation with ID is recommended for initial therapy. Test all isolates from DGI cases for antibiotic susceptibility, and send all isolates from DGI cases to the local public health laboratory.  

Report: all suspected and confirmed cases of DGI to public health within 24 hours of identification. Instruct patients to refer their sex partners for evaluation, testing, and presumptive treatment for gonorrhea.

 

This is Rio Bravo qWeek, your weekly dose of knowledge brought to you by the Rio Bravo Family Medicine Residency Program from Bakersfield, California. Our program is affiliated with UCLA, and it’s sponsored by Clinica Sierra Vista, Let Us Be Your Healthcare Home. 

Hepatic Encephalopathy
Guest: Stephanie Rubio, MS3

What is it?

Hepatic encephalopathy is a reversible decline in brain function in patients with advanced liver failure and/or portosystemic shunting and may present with ascites. The liver cannot effectively remove ammonia and other toxins from the blood causing a buildup in the bloodstream. Bacteria in the gut can also increase these toxins leading to a rapid progression of signs and symptoms of hepatic encephalopathy. 

 

How is the presentation?

A wide spectrum of neurological and/or psychiatric abnormalities may be seen, including but not limited to sleep disturbance, mood changes, and euphoria. Motor symptoms include asterixis, dyspraxia, and bizarre behavior.

 

A Subtle form of hepatic encephalopathy known as minimal hepatic encephalopathy presents in 80% of patients with cirrhosis. Neurocognitive signs require higher clinical suspicion because the deficits tend to be mild in presentation. 

 

Symptoms to look for while evaluating a patient with cirrhosis: 

Working memory discrepancies (for example, trying to remember a phone number and write it down, and being unable to recall the number within seconds)

Learning impairment (for example, inability to learn new concepts or skills, new recipe)

Inhibition control (for example, being unable to avoid eating cake when you are dieting) 

 

A brief mini mental status assessment will help guide toward a proper diagnosis. 

 

Severity of manifestations is graded due to the importance of differentiating between overt hepatic encephalopathy and covert minimal hepatic encephalopathy for clinical studies.

Minimal is graded as abnormal results on psychometric or neurophysiological testing without clinical manifestations vs. Grade I-IV beginning with changes in behavior, mild confusion, slurred speech, or disordered sleep; progressing to coma and unresponsiveness to pain.   

 

Who is at risk?

Some of the most common causes of liver failure or cirrhosis are patients with severe alcohol abuse, nonalcoholic steatohepatitis (NASH), or hepatitis. It affects 30-45% of patients with liver failure and 10-50% of patients with Transjugular Intrahepatic Portal-systemic Shunts (TIPS).  

 

Sarcopenia after TIPS has been identified as a risk for hepatic encephalopathy as well. Having muscle mass provides a protective effect against encephalopathy.

 

Inpatient management?

The management of hepatic encephalopathy would require a whole episode by itself. Management is focused on managing symptoms and identifying and treating the cause of the encephalopathy. Mild cases can be managed as outpatient, but admission is needed for severe cases, typically ICU admission.

 

To control symptoms, lactulose is the typical treatment used in the hospital, it is used to remove toxins by increasing the amount and number of stools. Initial dose: 30-45mL orally every hour until first stool, then reduce the dose to 30-45mL 3 to 4 times daily for a total of three soft stools a day. Lactulose can also be used rectally in patients who cannot use the PO route.

 

Other medications are used to reduce ammonia-producing bacteria in the intestines, such as Rifaximin (an antibiotic). Electrolyte imbalances may also occur in these patients and must be replenished as needed, frequently hypokalemia.

 

Identification and treatment of trigger requires a full investigation. Labs: CBC, CMP, ABG, PT/INR/PTT, hepatitis panel, Utox, blood culture and imaging as indicated by your clinical judgement.

 

How much benzo is safe?

Hepatic encephalopathy may lead to agitation in patients that frequently resolves with appropriate treatment. Though, the patient might be a hazard to self or others during periods of agitation. Restrains may be used initially. If pharmacological treatment is required, benzodiazepines should be avoided for two reasons. One, benzos may precipitate hepatic encephalopathy. Two, benzo’s may cause over sedation. 

 

However, signs and symptoms of agitation may be overlapping with alcohol withdrawal in patients who stopped drinking within 4 days of presentation of symptoms. In cases of severe agitation caused by alcohol withdrawal, 2mg lorazepam (Ativan) IV Q15 minutes until reaching the desired sedation level can be used. CIWA (Clinical Institute Withdrawal Assessment for Alcohol) <8 or RASS 0 to -1 (Richmond Agitation-Sedation Scale). Lorazepam use in the wards is generally safe. 

 

How much lorazepam is safe? It depends on your clinical judgement, but some patients may require up to 2,000 mg of lorazepam to control their initial agitation. For example, if you have a patient who is requiring more than 4 doses of 2-4 mg of lorazepam in a row.

 

To reiterate we must keep in mind, advanced cirrhotic patients may have amplified sensitivity to benzodiazepines due to increased receptor ligands in the brain which may lead to over sedation. Instead, haloperidol is the better option to avoid an adverse effect and aid in sedation to calm the patient. Haloperidol is used if your suspicion for alcohol withdrawals is low.

 

Prevention of hepatic encephalopathy.

Prevention of hepatic encephalopathy include avoiding precipitating factors such as:

Gastrointestinal bleeding, hypokalemia, metabolic acidosis, renal failure, hypoxia, hypoglycemia or constipation. Hepatic encephalopathy can reoccur after treatment; which is why prevention should be a patient/provider oriented goal to inhibit repetitive episodes.

 

Typically, after an occurrence, patients are discharged home with lactulose (initial dose: 30-45mL orally 3 to 4 times daily to have 2-3 bowel movements a day) to continue the removal of ammonia and further prevent complications. 

 

Probiotics may also aid to prevent reoccurrence, but more research is needed before probiotics can be recommended for all patients to treat and/or prevent hepatic encephalopathy.

 

Restricting dietary protein is not recommended for the majority of patients.

 

All of this discussion has led us to the question of: What if Homer Simpson is not stupid but just has chronic jaundice and hepatic encephalopathy? (Joke).

 

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Question of the Month: Polyarthralgia
Written by Claudia Carranza, MD
Answered by Stephanie Rubio, MS3

As a reminder, the question is about a 49-year-old female who comes to clinic with bilateral wrist and ankle pain for 1 month. She was diagnosed with COVID-19 six weeks ago, did not require hospitalization, but she complains of persistent fatigue. 

Question: What do you think is the etiology of this patient’s symptoms and what workup would you order (if any)? 

The patient’s polyarthralgia is the result of COVID-19. There are limited studies indicating coronavirus as a direct cause of polyarthralgia and fatigue, but in October 2020, The Lancet Rheumatology published an association between COVID-19 and ankle viral arthritis 25 days after her infection[5]. 

The association between COVID-19 and persistent symptoms has been well documented. Some persistent symptoms include fatigue, dyspnea, chest pain, cough, anxiety, depression, post-traumatic stress disorder, and poor memory and concentration. Joint pain is a less common symptom. Persistent symptoms are more common in patients with severe disease or 

those who were hospitalized. This syndrome may be unique to COVID-19 but other viral illnesses have similar presentation. 

Acute COVID-19 refers to symptoms for up to 4 weeks after onset of illness.

Ongoing symptomatic COVID-19 occurs 4-12 weeks after onset of illness.

Post-COVID-19 refers to persistent symptoms for more than 12 weeks, not explained by an alternative diagnosis.

In our patient, it’s reasonable to obtain CBC with diff and CMP. 

Autoantibodies tests such as ANA with reflex to titer and cascade may be ordered if your clinical suspicion is high for an autoimmune disease, such as SLE or RA, but are generally not needed. 

Imaging studies are not needed in our patient.

[Jokes provided by voluntarily-unidentified medical assistants]

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Now we conclude our episode number 46 “Hepatic Encephalopathy”, we thank our 3rd-year medical student Stephanie Rubio for preparing that discussion for us. We also congratulate her for winning our question of the month about polyarthralgia. We hope you enjoy your prize. During this episode, we were reminded that mild hepatic encephalopathy can be treated successfully as outpatient, but moderate to severe symptoms require hospital admission. Remember that lactulose and rifaximin can be used not only to treat hepatic encephalopathy but also to prevent it. Keep in mind our introduction today, keep your eyes open to detect new cases of disseminated gonococcal infections (DGI) and treat suspected cases accordingly. Remember, even without trying, every night you go to bed being a little wiser.

Thanks for listening to Rio Bravo qWeek. If you have any feedback about this podcast, contact us by email RBresidency@clinicasierravista.org, or visit our website riobravofmrp.org/qweek. This podcast was created with educational purposes only. Visit your primary care physician for additional medical advice. This week we thank Hector Arreaza, Jacqueline Uy, Claudia Carranza, Stephanie Rubio, Siamak Amrollahie, and Vikram Sharma. Audio edition by Suraj Amrutia. See you next week! 

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References:

Health and Human Services Agency California Department of Public Health, STD Control Branch,  https://www.cdph.ca.gov/Programs/CID/DCDC/CDPH%20Document%20Library/Dear-Colleague-Letter-for-Medical-Providers-Increasing-DGI-in-CA-12.23.20.pdf

 

Parisi, Simone; Richard Borrelli; Sabina Bianchi; Enrico Fusaro; Viral arthritis and COVID-19, The Lancet Rheumatology, October 05, 2020. DOI: https://doi.org/10.1016/S2665-9913(20)30348-9. https://www.thelancet.com/journals/lanrhe/article/PIIS2665-9913(20)30348-9/fulltext

 

Vilstrup H, Amodio P, Bajaj J, Cordoba J, Ferenci P, Mullen KD, Weissenborn K, Wong P. Hepatic encephalopathy in chronic liver disease: 2014 Practice Guideline by the American Association for the Study of Liver Diseases and the European Association for the Study of the Liver. Hepatology. 2014 Aug;60(2):715-35. doi: https://doi.org/10.1002/hep.27210. Epub 2014 Jul 8. PMID: 25042402.

 

Bajaj JS. Review article: the modern management of hepatic encephalopathy. Aliment Pharmacol Ther. 2010 Mar;31(5):537-47. doi: 10.1111/j.1365-2036.2009.04211.x. Epub 2009 Dec 7. PMID: 20002027.

 

Ferenci, P., MD. (2020, June 9). Uptodate. Retrieved March 16, 2021, from https://www.uptodate.com/contents/hepatic-encephalopathy-in-adults-treatment

 

Ferenci, P., MD. (2020, September 22). Uptodate. Retrieved March 16, 2021, from https://www.uptodate.com/contents/hepatic-encephalopathy-in-adults-clinical-manifestations-

 

Prabhakar, S., & Bhatia, R. (2003, December 22). Management of agitation and convulsions in hepatic encephalopathy. Retrieved March 16, 2021, from https://pubmed.ncbi.nlm.nih.gov/15025257/

 

Ciećko-Michalska, I., Szczepanek, M., Słowik, A., & Mach, T. (2012, December 17). Pathogenesis of hepatic encephalopathy. Retrieved March 16, 2021, from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3534214/

 

Nardelli S, Lattanzi B, Torrisi S, Greco F, Farcomeni A, Gioia S, Merli M, Riggio O. Sarcopenia Is Risk Factor for Development of Hepatic Encephalopathy After Transjugular Intrahepatic Portosystemic Shunt Placement. Clin Gastroenterol Hepatol. 2017 Jun;15(6):934-936. doi: https://doi.org/10.1016/j.cgh.2016.10.028. Epub 2016 Nov 2. PMID: 27816756.

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