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Hepatic Failure/GI/Endocrine Emergencies Stephanie N. Bass, Pharm.D., FCCP, BCCCP, BCPS Cleveland Clinic Cleveland, Ohio Mollie G. Lumpkin, Pharm.D., BCCCP, BCPS Cleveland Clinic Cleveland, Ohio…

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Hepatic Failure/GI/Endocrine Emergencies Hepatic Failure/GI/Endocrine Emergencies Stephanie N. Bass, Pharm.D., FCCP, BCCCP, BCPS Cleveland Clinic Cleveland, Ohio Mollie G. Lumpkin, Pharm.D., BCCCP,…

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Hepatic Failure/GI/Endocrine Emergencies Learning Objectives 1. Develop a treatment strategy to help manage and reduce the complications associated with acute liver failure (ALF). 2. Construct a p…

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Hepatic Failure/GI/Endocrine Emergencies 3. A 46-year-old man presents with alcohol-induced severe acute pancreatitis (AP). Pertinent medical history includes alcoholic cirrhosis and several admis-…

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Exam Content Outline 1 min

Hepatic Failure/GI/Endocrine Emergencies BPS Critical Care Pharmacy Examination Content Outline This chapter covers the following sections of the Critical Care Pharmacy Examination Content Outline: 1.…

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Hepatic Failure/GI/Endocrine Emergencies I.  ACUTE LIVER FAILURE A. Epidemiology 1. Incidence of ALF is less than 10 cases per 1 million individuals per year (2000 cases per year in the United Stat…

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Hepatic Failure/GI/Endocrine Emergencies 4. Patients with any degree of encephalopathy should be transferred to an ICU, ideally with contact to a transplant center, because rapid progression can occ…

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Hepatic Failure/GI/Endocrine Emergencies b. Unlike most other types of drug-induced liver injury (DILI), acetaminophen-induced liver failure is dose-dependent and predictable, and it is typically as…

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Hepatic Failure/GI/Endocrine Emergencies viii. The pattern of liver injury may also help identify drug causes. Hepatocellular injury (characterized by a marked elevation in transaminases with margin…

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Hepatic Failure/GI/Endocrine Emergencies d. Mushroom poisoning i. Typically caused by the Amanita phalloides spp. of mushrooms ii. Mushroom poisoning is classified as a hyperacute ALF with an onset…

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Hepatic Failure/GI/Endocrine Emergencies (b) Because ammonia is converted to osmotically active glutamine, concentrations have been correlated with both encephalopathy and cerebral edema. Ammonia co…

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Hepatic Failure/GI/Endocrine Emergencies iv. Spontaneous bleeding in patients with ALF, though uncommon, is capillary-type bleeding and usually results from mucosal bleeding in the stomach, lungs, o…

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Hepatic Failure/GI/Endocrine Emergencies (b) Many poison centers may extend therapy beyond the recommended course if there is a detectable acetaminophen concentration or if ALT concentrations contin…

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Hepatic Failure/GI/Endocrine Emergencies iv. Oral acetylcysteine has also been evaluated for the treatment of NAI-ALF in a prospective non-interventional study in which it, compared with a historica…

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Hepatic Failure/GI/Endocrine Emergencies 2. Management of neurologic complications a. Encephalopathy i. All medications that can cause sedation or confusion should be avoided (i.e., benzodiazepines…

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Hepatic Failure/GI/Endocrine Emergencies iii. Osmotic agents are used first line for control of ICP. (a) Mannitol has been used effectively in acutely reducing ICP in patients with ALF, though the…

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Hepatic Failure/GI/Endocrine Emergencies Patient Case 2. A 33-year-old man presents with ALF secondary to acetaminophen overdose. He is now 72 hours post-inges- tion and is profoundly encephalopathic…

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Hepatic Failure/GI/Endocrine Emergencies d. If clinically significant bleeding occurs, INR correction with fresh frozen plasma is warranted. i. Guidelines recommend an INR correction to about 1.5 fo…

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Hepatic Failure/GI/Endocrine Emergencies G. Advanced Therapies for ALF 1. Liver assist devices: The molecular adsorbent recirculating system (MARS) has been studied for the treatment of ALF. In a l…

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Hepatic Failure/GI/Endocrine Emergencies b. Moderately severe AP: Characterized by local complications and organ failure that lasts less than 48 hours. Local complications for moderately severe AP r…

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Hepatic Failure/GI/Endocrine Emergencies 3. Hypertriglyceridemia a. Primary and secondary hypertriglyceridemia are increasingly recognized as causes of AP (5%– 22% reported). b. If serum triglyceri…

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Hepatic Failure/GI/Endocrine Emergencies b. Early aggressive volume resuscitation (i.e., within the first 24 hours) has been shown to be more effective than later aggressive volume resuscitation. St…

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Hepatic Failure/GI/Endocrine Emergencies b. Endoscopic retrograde cholangiopancreatography (ERCP) i. Although many gallstones are passed through the duodenum and lost in the stool without causing h…

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Hepatic Failure/GI/Endocrine Emergencies 4. Nutrition a. Historically, patients were kept NPO in order to rest the pancreas and prevent the further release of pancreatic enzymes. Patients were give…

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Hepatic Failure/GI/Endocrine Emergencies Patient Case 3. A 44-year-old woman presents to the ED with a 2-day history of diffuse abdominal pain. Amylase is 700 IU/L, and lipase is 800 IU/L. She is gi…

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Hepatic Failure/GI/Endocrine Emergencies d. Fistulas can also be described according to whether they maintain continuity with the GI tract. i. Lateral fistulas divert off the intestines while mainta…

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Hepatic Failure/GI/Endocrine Emergencies 2. Drainage a. Drainage is used to prevent the accumulation of fluid and the development of infection. b. Most enterocutaneous fistulas will drain to skin s…

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Hepatic Failure/GI/Endocrine Emergencies c. Somatostatin significantly reduces output volumes. One prospective, randomized controlled single-center trial compared somatostatin 250 mcg/hour intraveno…

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Hepatic Failure/GI/Endocrine Emergencies Patient Case 4. A 34-year-old woman with morbid obesity presents to the surgical ICU after gastric bypass surgery 1 week prior with an enterocutaneous fistul…

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Hepatic Failure/GI/Endocrine Emergencies 2. During periods of fasting, upper GI tract motility is controlled by the migrating motor complex, which moves intestinal contents distally. a. During peri…

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Hepatic Failure/GI/Endocrine Emergencies 5. Sham feeding a. Sham feeding is the process of eliciting the release of hormonal and neuronal GI activity without regular feeding. One way by which this…

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Hepatic Failure/GI/Endocrine Emergencies (b) Alvimopan was studied in four North American phase III randomized controlled trials for POI. Each trial included adult surgical patients (generally bowel…

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Hepatic Failure/GI/Endocrine Emergencies Patient Case 5. A 40-year-old man presents for a large bowel resection. Because of the complexity of the procedure and the anticipated use of perioperative o…

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Hepatic Failure/GI/Endocrine Emergencies C. Prevention 1. A multimodal strategy that usually targets risk avoidance should be implemented to avoid PONV. The IMPACT study enrolled more than 5000 sur…

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Hepatic Failure/GI/Endocrine Emergencies d. Neurokinin-1 receptor antagonists (e.g., aprepitant) should be given at the time of induction. Data are limited on the use of neurokinin-1 receptor antago…

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Hepatic Failure/GI/Endocrine Emergencies 5. Mortality at 28 days after hospital admission for non-variceal hemorrhage is about 13%, whereas mortality after variceal hemorrhage is about 20%. Mortalit…

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Hepatic Failure/GI/Endocrine Emergencies 3. Bleeding ulcers may result in right upper quadrant pain. Mallory-Weiss tears may present as emesis, retching, or coughing before hematemesis. Patients wit…

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Hepatic Failure/GI/Endocrine Emergencies 3. Transfusion a. Current guidelines recommend a transfusion threshold of 7 g/dL for hospitalized hemodynamically stable patients, including those in the IC…

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Hepatic Failure/GI/Endocrine Emergencies (2) Endoscopic therapy for an adherent clot resistant to vigorous irrigation is controversial. Patients with clinical features associated with a higher risk…

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Hepatic Failure/GI/Endocrine Emergencies (c) When used without therapeutic endoscopy, octreotide is only marginally beneficial (i.e., reduction of packed red blood transfusion by 0.7 unit with no be…

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Hepatic Failure/GI/Endocrine Emergencies Patient Case 7. A 27-year-old man with a medical history of Crohn disease presents to your ED with frank bloody output from his rectum. The patient has hypot…

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Hepatic Failure/GI/Endocrine Emergencies 2. Antiplatelet therapy a. For patients on aspirin for secondary cardiovascular prevention who present with GI bleed, holding aspirin therapy is not recomme…

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Hepatic Failure/GI/Endocrine Emergencies 6. Adrenal crisis (i.e., acute adrenal insufficiency or Addisonian crisis) is a life-threatening disorder caused by glucocorticoid (and possibly mineralocort…

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Hepatic Failure/GI/Endocrine Emergencies e. Patients with HHS do not normally develop ketoacidosis. Although there is an overall insulin deficiency in both DKA and HHS, there is enough insulin secre…

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Hepatic Failure/GI/Endocrine Emergencies vii. Continuous insulin infusions should be continued until ketoacidosis resolves in DKA and abnormal serum osmolality and mental status in HHS resolve; then…

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Hepatic Failure/GI/Endocrine Emergencies b. Critically ill patients often do not have the “classic triad” of diabetes symptoms of polyuria, polydipsia, and polyphagia. c. Stress-induced hyperglycem…

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Hepatic Failure/GI/Endocrine Emergencies iii. A second multicenter study was terminated early because of several protocol violations. Intensive insulin therapy was not associated with a benefit in I…

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Hepatic Failure/GI/Endocrine Emergencies 2. Causes a. Hypoglycemia can be caused by excessive insulin administration, reduced intake of glucose (rarely the cause of severe hypoglycemia in the absen…

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Hepatic Failure/GI/Endocrine Emergencies i. Hyperthermia and diaphoresis are cardinal manifestations of thyroid crisis. Other key components include tachycardia out of proportion to fever and gastro…

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Hepatic Failure/GI/Endocrine Emergencies Criteria Points Precipitant history • Positive • Negative Score • > 44: Thyroid storm • 25–44: Suggestive/impending storm • < 25: Storm unlikely Information fr…

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Hepatic Failure/GI/Endocrine Emergencies iv. In patients who are allergic to iodine, lithium carbonate may be used as an alternative. Initial dose should be 300 mg every 6 hours, with subsequent adj…

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Hepatic Failure/GI/Endocrine Emergencies b. General treatment measures include rewarming of the patient and treatment of the precipitating illness. Because infection is a common precipitator of myxe…

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Hepatic Failure/GI/Endocrine Emergencies G. Adrenal insufficiency 1. Adrenal crisis a. Clinical presentation i. Because there is no universally accepted evidence-based definition of adrenal crisis…

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Hepatic Failure/GI/Endocrine Emergencies iv. Patients receiving chronic corticosteroids who have an acute stressor should receive an increased glucocorticoid dose to prevent adrenal crisis. (a) Rec…

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Hepatic Failure/GI/Endocrine Emergencies REFERENCES Acute Liver Failure Acharya SK, Bhatia V, Sreenivas V, Khanal S, Panda SK. Efficacy of L-ornithine L-aspartate in acute liver failure: a double-bl…

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Hepatic Failure/GI/Endocrine Emergencies Stravitz RT, Kramer AH, Davern T, et al. Intensive care of patients with acute liver failure: recommendations of the U.S. Acute Liver Failure Study Group. Cr…

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Hepatic Failure/GI/Endocrine Emergencies Gastrointestinal Fistulas Coughlin S, Roth L, Lurati G, Faulhaber M. Somatostatin analogues for the treatment of enterocutaneous fistu- las: a systematic revi…

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Hepatic Failure/GI/Endocrine Emergencies Gan TJ, Belani KG, Bergese S, et al. Fourth consensus guidelines for the management of postoperative nau- sea and vomiting. Anesth Analg. 2020;131(2):411-448.…

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Hepatic Failure/GI/Endocrine Emergencies Bañares R, Albillos A, Rincón D, et al. Endoscopic treatment versus endoscopic plus pharmaco- logic treatment for acute variceal bleeding: a meta-analysi…

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Hepatic Failure/GI/Endocrine Emergencies bleeds. Ann Pharmacother. 2019;53(8):794-800. https:// doi.org/10.1177/1060028019833696 Sachar H, Vaidya K, Laine L. Intermittent vs con- tinuous proton pump…

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Hepatic Failure/GI/Endocrine Emergencies Lancet. 2018;392(10141):31-40.  https://doi.org/10.1016/ s0140-6736(18)31080-8 Jonklaas J, Bianco AC, Bauer AJ, et al. Guidelines for the treatment of hypoth…

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Answers & Explanations 4 min

Hepatic Failure/GI/Endocrine Emergencies ANSWERS AND EXPLANATIONS TO PATIENT CASES 1. Answer: B Intravenous acetylcysteine increases transplant-free survival rates for patients with NAI-ALF, particu…

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Hepatic Failure/GI/Endocrine Emergencies (Answer C is incorrect). Although previous guidelines recommended initiating PPIs before endoscopy, the most recent version does not recommend for or against…

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Self-Assessment 5 min

Hepatic Failure/GI/Endocrine Emergencies ANSWERS AND EXPLANATIONS TO SELF-ASSESSMENT QUESTIONS 1. Answer: C The most recent guidelines from the American Association for the Study of Liver Diseases a…

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Hepatic Failure/GI/Endocrine Emergencies Appendix 1. Most Common or Well-Described Drugs Associated with DILI and the Patterns of Liver Injury Drug Class Typical Pattern of Injury Antibiotics •  Amoxi…

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