- Email: [email protected]
Mnemonic to Assist in Management of Liver Cirrhosis
Mnemonic to Assist in Management of Liver Cirrhosis Mohamed Toufic El Hussein, PhD, NP, James A. Rankin, PhD, ACNP, and Karen Lynn Then, PhD, NP ABSTRACT
Cirrhosis is a challenge for nurse practitioners in terms of providing effective management. The goals of this article are to provide readers with a general view of the pathophysiological complications of cirrhosis and to describe a mnemonic to assist in its management. Using mnemonics has been shown to reduce clinical errors and improve adherence to best practices. Mnemonics provide immediate access to relevant knowledge of complex concepts. The use of a mnemonics strategy in cirrhosis acts as an aid for translating pathophysiological and pharmaco-therapeutic concepts into meaningful interventions. Keywords: cirrhosis, liver, mnemonics, NP Ó 2018 Elsevier Inc. All rights reserved.
INTRODUCTION
M
nemonics are memory aids that allow rapid retrieval of data from memory.1 They can be structured to provide a systematic tool to navigate through a complicated clinical decision-making processes.2 Mnemonics help students recall information by encoding and organizing data in a fashion that makes information readily accessible, thus reducing stress and supporting the cognitive resources necessary for higher-order thinking.1 Thompson et al3 conducted a randomized controlled trial (RCT; n ¼ 29) to study the effects of using an alphabetical mnemonic in second-year osteopathic medical students on their ability to read lateral chest x-rays in the United States. Using a random approach, students were assigned to an intervention group (n ¼ 14) or a control group (n ¼ 15). The intervention group was given a mnemonic using the first eight letters of the alphabet. Both groups were given patient cases to review and document their observations of any pathological findings on lateral chest x-rays.
American Association of Nurse Practitioners (AANP) members may receive 1.0 continuing education contact hours, including 0.5 pharmacology credit, approved by AANP, by reading this article and completing the online posttest and evaluation at aanp.inreachce.com. 732
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Examination scores in the group that did not use the mnemonic were significantly lower compared with the group that use the mnemonic (79.9 vs 92, P ¼ .001). According to Putnam, the use of mnemonics in the classroom is hindered by the traditional expectation of strictly adhering to course objectives, arguing that classroom context is the major determinant of whether mnemonics can be used effectively.4 The lack of evidence to support that mnemonics have a positive impact on academic performance deterred some faculty from using them.4 McCabe and colleagues analyzed response from an online tool that explored 481 undergraduate students’ perception of mnemonics.5 They reported that students were not cognizant of the thinking process associated with mnemonics but rather only capable of mechanically regurgitating its letters. Students rated mnemonics as moderate in terms of usefulness compared with other learning strategies. In the context of cirrhosis, a mnemonic is used as a springboard to provide clinicians with a spark to ignite their memories and a tool to organize their thoughts. This article presents a general view of the complications of cirrhosis and describes a mnemonic designed to facilitate the role of nurse practitioners Volume 14, Issue 10, November/December 2018
(NPs) in slowing cirrhosis progression and minimizing its complications. The mnemonic is an alphabetical list from A to G that addresses the common complications of liver cirrhosis: Ascites, Bile stasis, Calcium and Vitamin D deficiencies, Encephalopathy, Factors deficiency, and Gastroesophageal varices.
Figure 2. Process of liver fibrosis (Andrew Reil created).
PATHOPHYSIOLOGY
Cirrhosis replaces the liver structure with dense fibrotic tissue due to a chronic process of inflammation and repair (Figure 1).6 Liver stellate cells differentiate into inflammatory extracellular matrixesecreting fibroblasts, which release collagen into the liver sinusoids leading to progressive obstruction inside the liver vasculature, and impairments in the liver synthetic and metabolic functions (Figure 2).7 DIAGNOSIS
Liver Fibroscan (Figure 3) is a diagnostic tool used to un-invasively assess liver fibrosis and stiffness,8 is interpreted with altered liver synthetic functions to affirm the condition of cirrhosis. Hepatic biopsy is not required unless its findings determine the treatment.9 According to the American Association for the Study of Liver Diseases practice guideline, patients with a liver stiffness less than 20 kPa have a less than 5% probability of having varices, and screening endoscopy is not recommended.10 In cirrhotic patients with liver stiffness greater than 20
kPa, screening endoscopy to diagnose gastroesophageal varices (GEV) is recommended to start prophylactic therapy.11 THE MNEMONIC
The alphabetical arrangement of 7 letters provides a structured and easy-to-recall approach for NPs to apply in clinical practice. Ascites is fluid collection in the peritoneal cavity and a popular complication of cirrhosis.12 According to Garcia-Tsao,13 the main cause of hepatic decompensation in general, and cirrhotic ascites in
Figure 1. Cirrhosis of the liver. Figure 3. Fibroscan.
Credit: Ed Uthman, Houston, TX, Creative Commons Attribution 2.0 Generic. www.npjournal.org
Used with permission from Echosens North America, Inc. The Journal for Nurse Practitioners - JNP
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particular, is portal hypertension (PH). In a seminal RCT investigation conducted in 2007 and cited more than 650 times (including citations in recent research studies and guidelines), Ripoll et al analyzed data from 213 patients in the United States with portal hypertension secondary to compensated cirrhosis without varices.14 The authors assessed indicators of hepatic decompensation including the occurrence of ascites, variceal hemorrhage, or hepatic encephalopathy. They evaluated the relationship between hepatic venous pressure gradient (HVPG) and clinical decompensation. Ripoll et al concluded that elevated HVPG is a strong indicator of hepatic decompensation. A rise of as little as 1 mm Hg in HVPG increased the incidence of clinical decompensation by 11%. After 4-year follow-up, Ripoll et al established that with an HVPG of less than 10 mm Hg, patients are 90% less likely to experience clinical decompensation. In another seminal double-blind, randomized, placebo-controlled trial (cited 761 times, including 2018 publications), Groszmann et al demonstrated that an HVPG of less than 12 mm Hg prevents the incidence variceal bleeding.15 The authors assessed hemodynamic parameters in cirrhotic patients with esophageal varices following either propranolol (n ¼ 51) or a placebo (n ¼ 51) intake. At 3 months, the HVPG in patients given propranolol decreased from 18.1 to 15.7 mm Hg (P < .05), whereas the HVPG in patients given placebo decreased from 19.8 to 17.5 (nonsignificant). Variceal hemorrhage occurred in 11 placebo treated patients, all of whom had a HVPG > 12 mm Hg (P < 0.01). In 14 of the propranolol treated patients, the HVPG decreased to less than 12 mm Hg and none of them developed variceal hemorrhage. Groszmann et al concluded that propranolol had a protective effect against variceal hemorrhage due to the reduction in HVPG.15 Thomson et al recommended that propranolol be prescribed as secondary prophylaxis for esophageal varices.16 Diuretics in combination with sodium restriction of 2 g/day are recommended for cirrhotic patients with ascites.17 Initially, the NP should start the patient on spironolactone 50 to 100 mg/day and gradually increase the dose up to 400 mg, depending on the degree of ascites. If ascites does not resolve 734
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within the first 2 weeks, the NP should add furosemide 20 to 40 mg/day and adjust the dose up to 160 mg unless the patient develops hyponatremia or ascites disappears.18 The NP must then exclude lack of adherence with dietary sodium restriction in patients who appear to be diuretic-resistant. In the setting of tense ascites, a paracentesis of 4e5 L has been shown to be more rapid in removing the ascitic fluid than diuretic therapy and does not require post-paracentesis colloid infusion because it is not associated with hemodynamic alterations.19 When more than 5 L are removed, albumin 6e8 g/L drained must be administered after the paracentesis to prevent post-paracentesiserelated circulatory dysfunction.12 An RCT (n ¼ 59) comparing cirrhotic patients who received albumin (n ¼ 30) with those who did not (n ¼29) established that mortality was higher in the latter (73% compared with 26%, P ¼ .03).20 Cirrhotic patients with ascites are at risk of developing spontaneous bacterial peritonitis (SBP), which is bacterial infection of the ascitic fluid often confirmed by the presence of polymorphonuclear leukocyte count of at least 250 cells/mm3.21 Infection increases mortality rates and worsens prognosis in cirrhotic patients. It is estimated that 27% of cirrhotic patients with infection die within a month and 47% die within a year.22 In a cross-sectional descriptive study conducted by El Amin et al in Egypt to evaluate the presence of infection in hospitalized cirrhotic patients, El Amin collected data from 100 cirrhotic patients admitted to tertiary care hospital and found that 61 of them were presenting with acute infections.23 SBP had the highest incidence of occurrence (44.3%), urinary tract infection was second (21.3%), followed by lung (19.7%), and gastrointestinal infections (6.6%). Poca et al completed a retrospective chart review (2001e2011) to develop a predictive model of inhospital mortality among 118 cirrhotic patients with SBP.24 They established that in-hospital mortality rate due to SBP was 28% (33/118) in cirrhotic patients. Once the diagnosis of SBP has been made, intravenous administration of cefotaxime for 5 days or amoxicillin/clavulanic acid or ciprofloxacin for 48 Volume 14, Issue 10, November/December 2018
hours should be initiated.25 In addition to antibiotics, intravenous albumin 1.5 g/kg is administered within the first six hours of diagnosis, followed by 1 g/kg on day 3.16 Garcia-Tsao et al conducted a multicenter RCT (n ¼ 431) to evaluate the overall survival rate in cirrhotic patients with ascites after receiving 40 g/ week of human albumin for 18 months.10 Mortality rates among patients given albumin was 38 of 218 (17.4%), whereas mortality rates in patients who were not given albumin was 46 of 213 (21.5%). The authors established that the mortality hazard ratio was reduced by 38% in the group that received human albumin (0.62, 95% confidence interval 0.40e0.95). In another RCT (n ¼ 777), conducted to examine the effect of albumin therapy on hyponatremia resolution and short-term survival, 225 patients received human albumin, and 349 did not. Patients who received intravenous albumin had a higher rate of hyponatremia resolution and better 30-day survival rate.26 Norfloxacin, a quinolone-based antibiotic, is recommended as primary prophylaxis against SBP.16 In a recent RCT (n ¼ 117) comparing norfloxacin with rifaximin use, as primary or secondary prophylaxis against SBP, the incidence of SBP was higher in patients receiving norfloxacin compared with patients who were given rifaximin as primary (20% vs 14%) or secondary (39% vs 7%) prophylaxis.27
Bile is an alkaline substance made by the hepatocytes. In cirrhotic patients, excessive fibrosis obstructs the sinusoids resulting in ineffective drainage of bile.28 Bile enters the circulation leading to jaundice and accumulates under the skin contributing to pruritus.29 Jaundice presents as yellowish discoloration of the skin, mucous membranes and sclera, occurring when serum bilirubin exceeds 34 mmol/L.29 The degradation of hemoglobin yields globin and heme. Heme is further broken down to bilirubin, which is a lipid soluble molecule. In the liver, bilirubin is conjugated to become a water-soluble molecule to be excreted in urine and feces.29 A cirrhotic liver cannot conjugate bilirubin, leading to its deposition in the sclera and skin resulting in the yellowish clinical feature. In rare cases, pruritus can be so severe that some patients commit suicide.30 Pharmacological therapies of bile acid sequestrants, such as cholestyramine (4 g 1e2 times/day) or colestipol (5 g once daily) should be prescribed for cirrhotic patients with pruritus.31 In cases where the bile acid sequestrants do not provide adequate relief, the NP can switch the patient to rifampin (150e300 mg twice daily), and if symptoms persist, an opioid antagonist, such as naltrexone, may be used (12.5e50 mg/day).31 Calcium serum levels are regulated by the parathyroid hormone secreted by the parathyroid
Figure 4. Mechanisms of calcium balance (Andrew Reil created).
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gland (Figure 4). In hypocalcemia, the level of parathyroid hormone is increased to move calcium from bones to blood.32 Musso, Juarez, and Glassock established that cirrhotic patients are at high risk for hypocalcemia and secondary metabolic bone disease.33 As may be seen from Figure 4, vitamin D is necessary for effective absorption of calcium from the intestines. Paternostro et al examined vitamin D levels in 199 cirrhotic patients and concluded that as cirrhosis worsens, vitamin D levels decrease, while mortality increases.34 The liver is instrumental in activating vitamin D. With limited activation of Vitamin D, less calcium will be absorbed and the patient may develop hypocalcemia (Musso, Juarez and Glassock (2018) Vitamin D is absorbed with fat from the intestines. With limited bile in the duodenum to emulsify ingested fat, less vitamin D will be absorbed, thus limiting calcium absorption and further complicating its homeostasis.35 Jha et al recommended 5,000 IU of vitamin D3 given daily for 3 months, followed by 1,000 IU/day as a lifelong supplement in cirrhotic patients with vitamin D levels less than 30 ng/ml.36 Encephalopathy is a deterioration in the function of the brain, primarily due to failure of the liver to detoxify lipid soluble ammonia to water-soluble urea. Ammonia accumulates in the blood, and crosses the bloodebrain barrier, disrupting the neurotransmitter function in the brain and leading to confusion.37 Lactulose is the initial therapy for hepatic encephalopathy. It creates an acidic environment when it is metabolized by colon bacteria to lactic acid. The acidic environment of the colon converts ammonia (NH3) into ammonium ions (NHþ4), slowing its absorption.38 To improve the patient’s mental status, lactulose 20 g/30 mL is administered every hour orally, or rectally by enema (300 g) to promote two to three bowel movements.37 Rifaximin 550 mg three times daily should be added if the patient suffers two episodes of overt hepatic encephalopathy while on lactulose. It inhibits the growth of enteric bacteria that produce ammonia as such lowering ammonia levels in the blood.39 Factors deficiency: with the exception of factor VIII, all clotting factors are made in the liver; therefore, patients with cirrhosis are at risk for 736
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bleeding.40 Vitamin K is essential for the liver to make vitamin Kedependent clotting factors II, VII, IX, and X. Although not enough studies were conducted to support the effectiveness of giving vitamin K in cirrhotic patients, vitamin K is still given at a dose of 10 mg/day orally for 3 days, or a single dose of 10 mg by infusion to overcome gastrointestinal absorption barriers caused ascites and gut edema.41 Gastroesophageal varices are dilated submucosal veins in the lower part of the esophagus that develop due to portal hypertension in cirrhotic patients. Portal hypertension is defined as pressure difference between the portal vein and the hepatic veins, of more than 5 mm Hg. According to AASLD practice guidance,10 PH ensues due reduced nitric oxide bioavailability and the excessive formation of fibrous tissue, which increase intrahepatic resistance to portal flow. In patients with PH but no GEV, the focus of therapy is the management of the underlying liver disease. Investigations showed preventative therapy before the onset of varices with nonselective beta blockers is futile.11 However primary prophylaxis is offered to all patients after the development of varices to prevent the first variceal hemorrhage and includes either endoscopic variceal ligation (EVL), or using a nonselective beta blocker. Endoscopic variceal ligation with rubber elastic bands are used for medium and large varices42 (Figure 5), whereas nonselective beta-blockers are used for small varices.
Figure 5. Variceal ligation with rubber elastic bands.
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The goal of pharmacological treatment is to decrease portal venous inflow, thus decreasing HVPG. According to Garcia-Tsao and Bosch,43 reducing HVPG by 20% or to less than 12 mm Hg remarkably reduces the incidence of variceal rebleeding. Propranolol, nadolol, and carvedilol are nonselective beta-blockers that block the adrenergic dilatory tone in the mesenteric arterioles, allowing uninhibited alpha-adrenergic mediated vasoconstriction, therefore decreasing portal pressure. Low-dose nonselective beta-blockers are titrated to maintain a resting heart rate between 55 to 60 beats/minute. Beta-blocker administration also reduces the risk of developing ascites and the incidence of SBP (Villanueva et al, 2015).44 CONCLUSION
This article has presented an overview of frequent complications of cirrhosis and the associated management, using an alphabetical mnemonic to help NPs readily access information and facilitate recall. The use of a mnemonic in the context of liver cirrhosis converts complex pathophysiological concepts into meaningful and succinct interventions. Using an alphabetical mnemonic provides a structured approach to liver cirrhosis that may improve adherence to best practices. References 1. Mocko M, Lesser LM, Wagler AE, Francis WS. Assessing effectiveness of mnemonics for tertiary students in a hybrid introductory statistics course. J Stat Educ. 2017;25(1):2-11. https://doi.org/10.1080/10691898. 2017.1294879. 2. Radhakrishna S, Walker L, Copeman P. LIVES a new mnemonic for teaching advanced airway management. Br J Anaesth. 2016;118:270-271. https://doi. org/10.1093/bja/el_13995. 3. Thompson M, Johansen D, Stoner R, Jarstad, et al. Comparative effectiveness of a mnemonic-use approach vs. self-study to interpret a lateral chest X-ray. Adv Physiol Educ. 2017;41(4):518-521. https://doi.org/10.1152/ advan.00034.2017. 4. Putnam AL. Mnemonics in education: current research and applications. Transl Issues Psychol Sci. 2015;1(2):130-139. https://doi.org/10.1037/ tps0000023. 5. McCabe JA, Osha KL, Roche JA, Susser JA. Psychology students’ knowledge and use of mnemonics. Teaching Psychol. 2013;40:183-192. https://doi.org/10. 1177/0098628313487460. 6. Fiore M, Leone S, Pace MC. Treatment of patients with cirrhosis. J Clin Gastroenterol Hepatol. 2017;1(1). https://doi.org/10.21767/2575-7733.1000005. 7. Tsochatzis EA, Bosch J, Burroughs AK. Liver cirrhosis. Lancet. 2014;383(9930):1749-1761. https://doi.org10.1016/s0140-6736(14)60121-5. 8. Berzigotti A. Non-invasive evaluation of portal hypertension using ultrasound elastography. J Hepatol. 2017;67(2):399-411. https://doi.org/10.1016/j.jhep. 2017.02.003. 9. Tsochatzis EA, Crossan C, Longworth L, et al. Cost-effectiveness of noninvasive liver fibrosis tests for treatment decisions in patients with chronic hepatitis C. Hepatology. 2014;60(3):832-843. https://doi.org/10.1002/ hep.27296.
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10. Garcia-Tsao G, Abraldes JG, Berzigotti A, Bosch J. Portal hypertensive bleeding in cirrhosis: risk stratification, diagnosis, and management: 2016 practice guidance by the American Association for the Study of Liver Diseases. Hepatology. 2016;65(1):310-335. https://doi.org/10.1002/hep.28906. 11. De Franchis R. Expanding consensus in portal hypertension. J Hepatol. 2015;63(3):743-752. https://doi.org10.1016/j.jhep.2015.05.022. 12. Adebayo D, Neong SF, Wong F. Refractory ascites in liver cirrhosis [Epub ahead of print]. Am J Gastroenterol. 2018. https://doi.org/10.1038/s41395-0180185-6. 13. Garcia-Tsao G. Long-term albumin in cirrhosis: is it the ANSWER? Lancet. 2018;391(10138):2391-2392. https://doi.org/10.1016/s0140-6736(18)30948-6. 14. Ripoll C, Groszmann R, Garcia-Tsao G, et al. Hepatic venous pressure gradient predicts clinical decompensation in patients with compensated cirrhosis. Gastroenterology. 2007;133(2):481-488. https://doi.org/10.1053/j. gastro.2007.05.024. 15. Groszmann RJ, Bosc J, Grace ND, et al. Hemodynamic events in a prospective randomized trial of propranolol versus placebo in the prevention of a first variceal hemorrhage. Gastroenterology. 1990;99(5):1401-1407. https://doi.org/10.1016/0016-5085(90)91168-6. 16. Thomson MJ, Tapper EB, Lok ASF. Dos and don’ts in the management of cirrhosis: a view from the 21st century. Am J Gastroenterol. 2018;113(7):927-931. https://doi.org/10.1038/s41395-018-0028-5. 17. Moore K. Diagnosis and management of ascites and hepatorenal syndrome (acute kidney injury) in cirrhosis. Medicine. 2015;43(11):674-678. https://doi. org10.1016/j.mpmed.2015.08.004. 18. Fukui H, Kawaratani H, Kaji K, Takaya H, Yoshiji H. Management of refractory cirrhotic ascites: challenges and solutions. Hepatic Med. 2018;10:55-71. http:// doi.org/10.2147/HMER.S136578. 19. Pose E, Cardenas A. Translating our current understanding of ascites management into new therapies for patients with cirrhosis and fluid retention. Digest Dis. 2017;35(4):402-410. https://doi.org/10.1159/000456595. 20. Arora V, Maiwall R, Thomas SS, et al. Albumin decreases the incidence of paracentesis induced circulatory dysfunction with less than 5 litres of ascitic tap in acute on chronic liver failure (ACLF) patients: randomized controlled trial (NCT02467348). J Hepatol. 2018;68:S42-S43. https://doi.org/10.1016/ s0168-8278(18)30303-9. 21. King JJ, Halliday N, Wey E, et al. The prognosis following bacterascites is as poor as spontaneous bacterial peritonitis. J Hepatol. 2018;68:S721-S722. https://doi.org/10.1016/s0168-8278(18)31704-5. 22. Gentile I, Buonomo AR, Scotto R, Zappulo E, Borgia G. Infections worsen prognosis of patients with cirrhosis irrespective of the liver disease stage. Eur J Int Med. 2017;46:e45-e47. https://doi.org/10.1016/j.ejim.2017. 09.014. 23. El-Amin H, Sabry AMM, Ahmed RE, Makhlouf NA. Types and microbiological spectrum of infections in patients with cirrhosis: a single-centre experience in Upper Egypt. Arab J Gastroenterol. 2017;18(3):159-164. https://doi.org/10. 1016/j.ajg.2017.09.005. 24. Poca M, Alvarado E, Conceptión M, et al. P0190: Predictive model of mortality in cirrhotic patients with high risk spontaneous bacterial peritonitis. J Hepatol. 2016;62:S375. https://doi.org/10.1016/s0168-8278(15)30409-8. 25. Fiore M, Gentile I, Maraolo AE, et al. Are third-generation cephalosporins still the empirical antibiotic treatment of community-acquired spontaneous bacterial peritonitis? A systematic review and meta-analysis. Eur J Gastroenterol Hepatol. 2018;30(3):329-336. https://doi.org/10.1097/meg. 0000000000001057. 26. Bajaj JS, Tandon P, O’Leary JG, et al. The impact of albumin use on resolution of hyponatremia in hospitalized patients with cirrhosis. Am J Gastroenterol. 2018;113:339-1344. https://doi.org/10.1038/s41395-018-0119-3. 27. Praharaj D, Taneja S, Duseja A, Chawla YK, Dhiman RK. Randomized control trial of rifaximin and norfloxacin in primary and secondary prophylaxis of spontaneous bacterial peritonitis (SBP) in cirrhotic patients. J Clini Exp Hepatol. 2017;7:S71. https://doi.org/10.1016/j.jceh. 2017.05.133. 28. Khan RS, Houlihan DD, Newsome PN. Investigation of jaundice. Medicine. 2015;43(10):573-576. https://doi.org10.1016/j.mpmed.2015.07. 009. 29. Berger L, Garcia Popov A, Berger B. Case report: Relieving the itch of cholestasis with corticosteroids in palliative care. J Palliative Med. 2015;18(11):913-914. https://doi.org/10.1089/jpm.2015.0304. 30. Prabhakar D, Peterson EL, Hu Y, et al. Dermatologic conditions and risk of suicide: a case-control study. Psychosomatics. 2018;59(1):58-61. https://doi. org/10.1016/j.psym.2017.08.001. 31. Carrion AF, Rosen JD, Levy C. Understanding and treating pruritus in primary biliary cholangitis. Clin Liver Dis. 2018;22(3):517-532. https://doi.org/10.1016/j. cld.2018.03.005. 32. Ströhle A, Hadji P, Hahn A. Calcium and bone health—goodbye, calcium supplements? Climacteric. 2015;18(5):702-714. https://doi.org/10.3109/ 13697137.2015.1016419.
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33. Musso CG, Juarez R, Glassock RJ. Water, electrolyte, acidebase, and trace elements alterations in cirrhotic patients. Int Urol Nephrol. 2017;50(1):81-89. https://doi.org/10.1007/s11255-017-1614-y. 34. Paternostro R, Wagner D, Reiberger T, et al. Low 25-OH-vitamin D levels reflect hepatic dysfunction and are associated with mortality in patients with liver cirrhosis. Wien Klin Wochenschr. 2016;129(1-2):8-15. https://doi.org/10. 1007/s00508-016-1127-1. 35. Konstantakis C, Tselekouni P, Kalafateli M, Triantos C. Vitamin D deficiency in patients with liver cirrhosis. Ann Gastroenterol. 2016;29(3):297-306. https:// doi.org10.20524/aog.2016.0037. 36. AK, Jha SK, Kumar A, Dayal VM, Jha SK. Effect of replenishment of vitamin D on survival in patients with decompensated liver cirrhosis: a prospective study. World J Gastrointest Pathophysiol. 2017;8(3):133. https://doi.org/10. 4291/wjgp.v8.i3.133. 37. Vilstrup H, Amodio P, Bajaj K, et al. Hepatic encephalopathy in chronic liver disease: 2014 practice guideline by the European Association for the Study of the Liver and the American Association for the Study of Liver Diseases. J Hepatol. 2014;61(3):642-659. https://doi.org10.1016/j.jhep. 2014.05.042. 38. Fitzpatrick S, Domingo HDA, Finke SM. The care of the decompensated cirrhotic patient. J Nurse Pract. 2017;13(4):256-263. https://doi.org10.1016/j. nurpra.2016.11.026. 39. Kimer N, Krag A, Møller S, Bendtsen F, Gluud LL. Systematic review with meta-analysis: the effects of rifaximin in hepatic encephalopathy. Aliment Pharmacol Ther. 2014;40(2):123-132. https://doi.org/10.1111/apt.12803. 40. Deutsch M, Koskinas J. Antiplatelets and antithrombotics in patients with liver insufficiency: from pathophysiology to clinical practice. Curr Pharm Design. 2017;23(9):1346-1353. https://doi.org/10.2174/ 1381612822666161205113629. 41. Shah N, Caldwell S. Hemostatic abnormalities in patients with liver disease. UpToDate. 2017. Retrieved from https://www.uptodate.com/contents/ hemostatic-abnormalities-in-patients-with-liver-disease. 42. Ge PS, Runyon BA. The changing role of beta-blocker therapy in patients with cirrhosis. J Hepatol. 2014;60(3):643-653. https://doi.org10.1016/j.jhep.2013.09. 016.
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43. Garcia-Tsao G, Bosch J. Varices and variceal hemorrhage in cirrhosis: a new view of an old problem. Clin Gastroenterol Hepatol. 2015;13(12):2109-2117. https://doi.org/10.1016/j.cgh.2015.07.012. 44. Villanueva C, Albillos A, Genescà J, et al. Development of hyperdynamic circulation and response to b-blockers in compensated cirrhosis with portal hypertension. Hepatology. 2016;63(1):197-206. https://doi.org/10.1002/hep. 28264.
Mohamed Toufic El Hussein, PhD, NP, is an associate professor in the School of Nursing and Midwifery, Faculty of Health, Community & Education, Mount Royal University, Calgary, AB, Canada. He is available at [email protected]. James A. Rankin, PhD, ACNP, is a professor and acute care nurse practitioner at the University of Calgary/Alberta Health Services, Calgary, Alberta, Canada. Karen Lynn Then, PhD, NP, is a professor and acute care nurse practitioner at the University of Calgary/Alberta Health Services, Calgary, Alberta, Canada. In compliance with national ethical guidelines, the authors report no relationships with business or industry that would pose a conflict of interest. 1555-4155/18/$ see front matter © 2018 Elsevier Inc. All rights reserved. https://doi.org/10.1016/j.nurpra.2018.08.032
Volume 14, Issue 10, November/December 2018
Cirrhosis is a challenge for nurse practitioners in terms of providing effective management. The goals of this article are to provide readers with a general view of the pathophysiological complications of cirrhosis and to describe a mnemonic to assist in its management. Using mnemonics has been shown to reduce clinical errors and improve adherence to best practices. Mnemonics provide immediate access to relevant knowledge of complex concepts. The use of a mnemonics strategy in cirrhosis acts as an aid for translating pathophysiological and pharmaco-therapeutic concepts into meaningful interventions. Keywords: cirrhosis, liver, mnemonics, NP Ó 2018 Elsevier Inc. All rights reserved.
INTRODUCTION
M
nemonics are memory aids that allow rapid retrieval of data from memory.1 They can be structured to provide a systematic tool to navigate through a complicated clinical decision-making processes.2 Mnemonics help students recall information by encoding and organizing data in a fashion that makes information readily accessible, thus reducing stress and supporting the cognitive resources necessary for higher-order thinking.1 Thompson et al3 conducted a randomized controlled trial (RCT; n ¼ 29) to study the effects of using an alphabetical mnemonic in second-year osteopathic medical students on their ability to read lateral chest x-rays in the United States. Using a random approach, students were assigned to an intervention group (n ¼ 14) or a control group (n ¼ 15). The intervention group was given a mnemonic using the first eight letters of the alphabet. Both groups were given patient cases to review and document their observations of any pathological findings on lateral chest x-rays.
American Association of Nurse Practitioners (AANP) members may receive 1.0 continuing education contact hours, including 0.5 pharmacology credit, approved by AANP, by reading this article and completing the online posttest and evaluation at aanp.inreachce.com. 732
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Examination scores in the group that did not use the mnemonic were significantly lower compared with the group that use the mnemonic (79.9 vs 92, P ¼ .001). According to Putnam, the use of mnemonics in the classroom is hindered by the traditional expectation of strictly adhering to course objectives, arguing that classroom context is the major determinant of whether mnemonics can be used effectively.4 The lack of evidence to support that mnemonics have a positive impact on academic performance deterred some faculty from using them.4 McCabe and colleagues analyzed response from an online tool that explored 481 undergraduate students’ perception of mnemonics.5 They reported that students were not cognizant of the thinking process associated with mnemonics but rather only capable of mechanically regurgitating its letters. Students rated mnemonics as moderate in terms of usefulness compared with other learning strategies. In the context of cirrhosis, a mnemonic is used as a springboard to provide clinicians with a spark to ignite their memories and a tool to organize their thoughts. This article presents a general view of the complications of cirrhosis and describes a mnemonic designed to facilitate the role of nurse practitioners Volume 14, Issue 10, November/December 2018
(NPs) in slowing cirrhosis progression and minimizing its complications. The mnemonic is an alphabetical list from A to G that addresses the common complications of liver cirrhosis: Ascites, Bile stasis, Calcium and Vitamin D deficiencies, Encephalopathy, Factors deficiency, and Gastroesophageal varices.
Figure 2. Process of liver fibrosis (Andrew Reil created).
PATHOPHYSIOLOGY
Cirrhosis replaces the liver structure with dense fibrotic tissue due to a chronic process of inflammation and repair (Figure 1).6 Liver stellate cells differentiate into inflammatory extracellular matrixesecreting fibroblasts, which release collagen into the liver sinusoids leading to progressive obstruction inside the liver vasculature, and impairments in the liver synthetic and metabolic functions (Figure 2).7 DIAGNOSIS
Liver Fibroscan (Figure 3) is a diagnostic tool used to un-invasively assess liver fibrosis and stiffness,8 is interpreted with altered liver synthetic functions to affirm the condition of cirrhosis. Hepatic biopsy is not required unless its findings determine the treatment.9 According to the American Association for the Study of Liver Diseases practice guideline, patients with a liver stiffness less than 20 kPa have a less than 5% probability of having varices, and screening endoscopy is not recommended.10 In cirrhotic patients with liver stiffness greater than 20
kPa, screening endoscopy to diagnose gastroesophageal varices (GEV) is recommended to start prophylactic therapy.11 THE MNEMONIC
The alphabetical arrangement of 7 letters provides a structured and easy-to-recall approach for NPs to apply in clinical practice. Ascites is fluid collection in the peritoneal cavity and a popular complication of cirrhosis.12 According to Garcia-Tsao,13 the main cause of hepatic decompensation in general, and cirrhotic ascites in
Figure 1. Cirrhosis of the liver. Figure 3. Fibroscan.
Credit: Ed Uthman, Houston, TX, Creative Commons Attribution 2.0 Generic. www.npjournal.org
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particular, is portal hypertension (PH). In a seminal RCT investigation conducted in 2007 and cited more than 650 times (including citations in recent research studies and guidelines), Ripoll et al analyzed data from 213 patients in the United States with portal hypertension secondary to compensated cirrhosis without varices.14 The authors assessed indicators of hepatic decompensation including the occurrence of ascites, variceal hemorrhage, or hepatic encephalopathy. They evaluated the relationship between hepatic venous pressure gradient (HVPG) and clinical decompensation. Ripoll et al concluded that elevated HVPG is a strong indicator of hepatic decompensation. A rise of as little as 1 mm Hg in HVPG increased the incidence of clinical decompensation by 11%. After 4-year follow-up, Ripoll et al established that with an HVPG of less than 10 mm Hg, patients are 90% less likely to experience clinical decompensation. In another seminal double-blind, randomized, placebo-controlled trial (cited 761 times, including 2018 publications), Groszmann et al demonstrated that an HVPG of less than 12 mm Hg prevents the incidence variceal bleeding.15 The authors assessed hemodynamic parameters in cirrhotic patients with esophageal varices following either propranolol (n ¼ 51) or a placebo (n ¼ 51) intake. At 3 months, the HVPG in patients given propranolol decreased from 18.1 to 15.7 mm Hg (P < .05), whereas the HVPG in patients given placebo decreased from 19.8 to 17.5 (nonsignificant). Variceal hemorrhage occurred in 11 placebo treated patients, all of whom had a HVPG > 12 mm Hg (P < 0.01). In 14 of the propranolol treated patients, the HVPG decreased to less than 12 mm Hg and none of them developed variceal hemorrhage. Groszmann et al concluded that propranolol had a protective effect against variceal hemorrhage due to the reduction in HVPG.15 Thomson et al recommended that propranolol be prescribed as secondary prophylaxis for esophageal varices.16 Diuretics in combination with sodium restriction of 2 g/day are recommended for cirrhotic patients with ascites.17 Initially, the NP should start the patient on spironolactone 50 to 100 mg/day and gradually increase the dose up to 400 mg, depending on the degree of ascites. If ascites does not resolve 734
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within the first 2 weeks, the NP should add furosemide 20 to 40 mg/day and adjust the dose up to 160 mg unless the patient develops hyponatremia or ascites disappears.18 The NP must then exclude lack of adherence with dietary sodium restriction in patients who appear to be diuretic-resistant. In the setting of tense ascites, a paracentesis of 4e5 L has been shown to be more rapid in removing the ascitic fluid than diuretic therapy and does not require post-paracentesis colloid infusion because it is not associated with hemodynamic alterations.19 When more than 5 L are removed, albumin 6e8 g/L drained must be administered after the paracentesis to prevent post-paracentesiserelated circulatory dysfunction.12 An RCT (n ¼ 59) comparing cirrhotic patients who received albumin (n ¼ 30) with those who did not (n ¼29) established that mortality was higher in the latter (73% compared with 26%, P ¼ .03).20 Cirrhotic patients with ascites are at risk of developing spontaneous bacterial peritonitis (SBP), which is bacterial infection of the ascitic fluid often confirmed by the presence of polymorphonuclear leukocyte count of at least 250 cells/mm3.21 Infection increases mortality rates and worsens prognosis in cirrhotic patients. It is estimated that 27% of cirrhotic patients with infection die within a month and 47% die within a year.22 In a cross-sectional descriptive study conducted by El Amin et al in Egypt to evaluate the presence of infection in hospitalized cirrhotic patients, El Amin collected data from 100 cirrhotic patients admitted to tertiary care hospital and found that 61 of them were presenting with acute infections.23 SBP had the highest incidence of occurrence (44.3%), urinary tract infection was second (21.3%), followed by lung (19.7%), and gastrointestinal infections (6.6%). Poca et al completed a retrospective chart review (2001e2011) to develop a predictive model of inhospital mortality among 118 cirrhotic patients with SBP.24 They established that in-hospital mortality rate due to SBP was 28% (33/118) in cirrhotic patients. Once the diagnosis of SBP has been made, intravenous administration of cefotaxime for 5 days or amoxicillin/clavulanic acid or ciprofloxacin for 48 Volume 14, Issue 10, November/December 2018
hours should be initiated.25 In addition to antibiotics, intravenous albumin 1.5 g/kg is administered within the first six hours of diagnosis, followed by 1 g/kg on day 3.16 Garcia-Tsao et al conducted a multicenter RCT (n ¼ 431) to evaluate the overall survival rate in cirrhotic patients with ascites after receiving 40 g/ week of human albumin for 18 months.10 Mortality rates among patients given albumin was 38 of 218 (17.4%), whereas mortality rates in patients who were not given albumin was 46 of 213 (21.5%). The authors established that the mortality hazard ratio was reduced by 38% in the group that received human albumin (0.62, 95% confidence interval 0.40e0.95). In another RCT (n ¼ 777), conducted to examine the effect of albumin therapy on hyponatremia resolution and short-term survival, 225 patients received human albumin, and 349 did not. Patients who received intravenous albumin had a higher rate of hyponatremia resolution and better 30-day survival rate.26 Norfloxacin, a quinolone-based antibiotic, is recommended as primary prophylaxis against SBP.16 In a recent RCT (n ¼ 117) comparing norfloxacin with rifaximin use, as primary or secondary prophylaxis against SBP, the incidence of SBP was higher in patients receiving norfloxacin compared with patients who were given rifaximin as primary (20% vs 14%) or secondary (39% vs 7%) prophylaxis.27
Bile is an alkaline substance made by the hepatocytes. In cirrhotic patients, excessive fibrosis obstructs the sinusoids resulting in ineffective drainage of bile.28 Bile enters the circulation leading to jaundice and accumulates under the skin contributing to pruritus.29 Jaundice presents as yellowish discoloration of the skin, mucous membranes and sclera, occurring when serum bilirubin exceeds 34 mmol/L.29 The degradation of hemoglobin yields globin and heme. Heme is further broken down to bilirubin, which is a lipid soluble molecule. In the liver, bilirubin is conjugated to become a water-soluble molecule to be excreted in urine and feces.29 A cirrhotic liver cannot conjugate bilirubin, leading to its deposition in the sclera and skin resulting in the yellowish clinical feature. In rare cases, pruritus can be so severe that some patients commit suicide.30 Pharmacological therapies of bile acid sequestrants, such as cholestyramine (4 g 1e2 times/day) or colestipol (5 g once daily) should be prescribed for cirrhotic patients with pruritus.31 In cases where the bile acid sequestrants do not provide adequate relief, the NP can switch the patient to rifampin (150e300 mg twice daily), and if symptoms persist, an opioid antagonist, such as naltrexone, may be used (12.5e50 mg/day).31 Calcium serum levels are regulated by the parathyroid hormone secreted by the parathyroid
Figure 4. Mechanisms of calcium balance (Andrew Reil created).
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gland (Figure 4). In hypocalcemia, the level of parathyroid hormone is increased to move calcium from bones to blood.32 Musso, Juarez, and Glassock established that cirrhotic patients are at high risk for hypocalcemia and secondary metabolic bone disease.33 As may be seen from Figure 4, vitamin D is necessary for effective absorption of calcium from the intestines. Paternostro et al examined vitamin D levels in 199 cirrhotic patients and concluded that as cirrhosis worsens, vitamin D levels decrease, while mortality increases.34 The liver is instrumental in activating vitamin D. With limited activation of Vitamin D, less calcium will be absorbed and the patient may develop hypocalcemia (Musso, Juarez and Glassock (2018) Vitamin D is absorbed with fat from the intestines. With limited bile in the duodenum to emulsify ingested fat, less vitamin D will be absorbed, thus limiting calcium absorption and further complicating its homeostasis.35 Jha et al recommended 5,000 IU of vitamin D3 given daily for 3 months, followed by 1,000 IU/day as a lifelong supplement in cirrhotic patients with vitamin D levels less than 30 ng/ml.36 Encephalopathy is a deterioration in the function of the brain, primarily due to failure of the liver to detoxify lipid soluble ammonia to water-soluble urea. Ammonia accumulates in the blood, and crosses the bloodebrain barrier, disrupting the neurotransmitter function in the brain and leading to confusion.37 Lactulose is the initial therapy for hepatic encephalopathy. It creates an acidic environment when it is metabolized by colon bacteria to lactic acid. The acidic environment of the colon converts ammonia (NH3) into ammonium ions (NHþ4), slowing its absorption.38 To improve the patient’s mental status, lactulose 20 g/30 mL is administered every hour orally, or rectally by enema (300 g) to promote two to three bowel movements.37 Rifaximin 550 mg three times daily should be added if the patient suffers two episodes of overt hepatic encephalopathy while on lactulose. It inhibits the growth of enteric bacteria that produce ammonia as such lowering ammonia levels in the blood.39 Factors deficiency: with the exception of factor VIII, all clotting factors are made in the liver; therefore, patients with cirrhosis are at risk for 736
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bleeding.40 Vitamin K is essential for the liver to make vitamin Kedependent clotting factors II, VII, IX, and X. Although not enough studies were conducted to support the effectiveness of giving vitamin K in cirrhotic patients, vitamin K is still given at a dose of 10 mg/day orally for 3 days, or a single dose of 10 mg by infusion to overcome gastrointestinal absorption barriers caused ascites and gut edema.41 Gastroesophageal varices are dilated submucosal veins in the lower part of the esophagus that develop due to portal hypertension in cirrhotic patients. Portal hypertension is defined as pressure difference between the portal vein and the hepatic veins, of more than 5 mm Hg. According to AASLD practice guidance,10 PH ensues due reduced nitric oxide bioavailability and the excessive formation of fibrous tissue, which increase intrahepatic resistance to portal flow. In patients with PH but no GEV, the focus of therapy is the management of the underlying liver disease. Investigations showed preventative therapy before the onset of varices with nonselective beta blockers is futile.11 However primary prophylaxis is offered to all patients after the development of varices to prevent the first variceal hemorrhage and includes either endoscopic variceal ligation (EVL), or using a nonselective beta blocker. Endoscopic variceal ligation with rubber elastic bands are used for medium and large varices42 (Figure 5), whereas nonselective beta-blockers are used for small varices.
Figure 5. Variceal ligation with rubber elastic bands.
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The goal of pharmacological treatment is to decrease portal venous inflow, thus decreasing HVPG. According to Garcia-Tsao and Bosch,43 reducing HVPG by 20% or to less than 12 mm Hg remarkably reduces the incidence of variceal rebleeding. Propranolol, nadolol, and carvedilol are nonselective beta-blockers that block the adrenergic dilatory tone in the mesenteric arterioles, allowing uninhibited alpha-adrenergic mediated vasoconstriction, therefore decreasing portal pressure. Low-dose nonselective beta-blockers are titrated to maintain a resting heart rate between 55 to 60 beats/minute. Beta-blocker administration also reduces the risk of developing ascites and the incidence of SBP (Villanueva et al, 2015).44 CONCLUSION
This article has presented an overview of frequent complications of cirrhosis and the associated management, using an alphabetical mnemonic to help NPs readily access information and facilitate recall. The use of a mnemonic in the context of liver cirrhosis converts complex pathophysiological concepts into meaningful and succinct interventions. Using an alphabetical mnemonic provides a structured approach to liver cirrhosis that may improve adherence to best practices. References 1. Mocko M, Lesser LM, Wagler AE, Francis WS. Assessing effectiveness of mnemonics for tertiary students in a hybrid introductory statistics course. J Stat Educ. 2017;25(1):2-11. https://doi.org/10.1080/10691898. 2017.1294879. 2. Radhakrishna S, Walker L, Copeman P. LIVES a new mnemonic for teaching advanced airway management. Br J Anaesth. 2016;118:270-271. https://doi. org/10.1093/bja/el_13995. 3. Thompson M, Johansen D, Stoner R, Jarstad, et al. Comparative effectiveness of a mnemonic-use approach vs. self-study to interpret a lateral chest X-ray. Adv Physiol Educ. 2017;41(4):518-521. https://doi.org/10.1152/ advan.00034.2017. 4. Putnam AL. Mnemonics in education: current research and applications. Transl Issues Psychol Sci. 2015;1(2):130-139. https://doi.org/10.1037/ tps0000023. 5. McCabe JA, Osha KL, Roche JA, Susser JA. Psychology students’ knowledge and use of mnemonics. Teaching Psychol. 2013;40:183-192. https://doi.org/10. 1177/0098628313487460. 6. Fiore M, Leone S, Pace MC. Treatment of patients with cirrhosis. J Clin Gastroenterol Hepatol. 2017;1(1). https://doi.org/10.21767/2575-7733.1000005. 7. Tsochatzis EA, Bosch J, Burroughs AK. Liver cirrhosis. Lancet. 2014;383(9930):1749-1761. https://doi.org10.1016/s0140-6736(14)60121-5. 8. Berzigotti A. Non-invasive evaluation of portal hypertension using ultrasound elastography. J Hepatol. 2017;67(2):399-411. https://doi.org/10.1016/j.jhep. 2017.02.003. 9. Tsochatzis EA, Crossan C, Longworth L, et al. Cost-effectiveness of noninvasive liver fibrosis tests for treatment decisions in patients with chronic hepatitis C. Hepatology. 2014;60(3):832-843. https://doi.org/10.1002/ hep.27296.
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10. Garcia-Tsao G, Abraldes JG, Berzigotti A, Bosch J. Portal hypertensive bleeding in cirrhosis: risk stratification, diagnosis, and management: 2016 practice guidance by the American Association for the Study of Liver Diseases. Hepatology. 2016;65(1):310-335. https://doi.org/10.1002/hep.28906. 11. De Franchis R. Expanding consensus in portal hypertension. J Hepatol. 2015;63(3):743-752. https://doi.org10.1016/j.jhep.2015.05.022. 12. Adebayo D, Neong SF, Wong F. Refractory ascites in liver cirrhosis [Epub ahead of print]. Am J Gastroenterol. 2018. https://doi.org/10.1038/s41395-0180185-6. 13. Garcia-Tsao G. Long-term albumin in cirrhosis: is it the ANSWER? Lancet. 2018;391(10138):2391-2392. https://doi.org/10.1016/s0140-6736(18)30948-6. 14. Ripoll C, Groszmann R, Garcia-Tsao G, et al. Hepatic venous pressure gradient predicts clinical decompensation in patients with compensated cirrhosis. Gastroenterology. 2007;133(2):481-488. https://doi.org/10.1053/j. gastro.2007.05.024. 15. Groszmann RJ, Bosc J, Grace ND, et al. Hemodynamic events in a prospective randomized trial of propranolol versus placebo in the prevention of a first variceal hemorrhage. Gastroenterology. 1990;99(5):1401-1407. https://doi.org/10.1016/0016-5085(90)91168-6. 16. Thomson MJ, Tapper EB, Lok ASF. Dos and don’ts in the management of cirrhosis: a view from the 21st century. Am J Gastroenterol. 2018;113(7):927-931. https://doi.org/10.1038/s41395-018-0028-5. 17. Moore K. Diagnosis and management of ascites and hepatorenal syndrome (acute kidney injury) in cirrhosis. Medicine. 2015;43(11):674-678. https://doi. org10.1016/j.mpmed.2015.08.004. 18. Fukui H, Kawaratani H, Kaji K, Takaya H, Yoshiji H. Management of refractory cirrhotic ascites: challenges and solutions. Hepatic Med. 2018;10:55-71. http:// doi.org/10.2147/HMER.S136578. 19. Pose E, Cardenas A. Translating our current understanding of ascites management into new therapies for patients with cirrhosis and fluid retention. Digest Dis. 2017;35(4):402-410. https://doi.org/10.1159/000456595. 20. Arora V, Maiwall R, Thomas SS, et al. Albumin decreases the incidence of paracentesis induced circulatory dysfunction with less than 5 litres of ascitic tap in acute on chronic liver failure (ACLF) patients: randomized controlled trial (NCT02467348). J Hepatol. 2018;68:S42-S43. https://doi.org/10.1016/ s0168-8278(18)30303-9. 21. King JJ, Halliday N, Wey E, et al. The prognosis following bacterascites is as poor as spontaneous bacterial peritonitis. J Hepatol. 2018;68:S721-S722. https://doi.org/10.1016/s0168-8278(18)31704-5. 22. Gentile I, Buonomo AR, Scotto R, Zappulo E, Borgia G. Infections worsen prognosis of patients with cirrhosis irrespective of the liver disease stage. Eur J Int Med. 2017;46:e45-e47. https://doi.org/10.1016/j.ejim.2017. 09.014. 23. El-Amin H, Sabry AMM, Ahmed RE, Makhlouf NA. Types and microbiological spectrum of infections in patients with cirrhosis: a single-centre experience in Upper Egypt. Arab J Gastroenterol. 2017;18(3):159-164. https://doi.org/10. 1016/j.ajg.2017.09.005. 24. Poca M, Alvarado E, Conceptión M, et al. P0190: Predictive model of mortality in cirrhotic patients with high risk spontaneous bacterial peritonitis. J Hepatol. 2016;62:S375. https://doi.org/10.1016/s0168-8278(15)30409-8. 25. Fiore M, Gentile I, Maraolo AE, et al. Are third-generation cephalosporins still the empirical antibiotic treatment of community-acquired spontaneous bacterial peritonitis? A systematic review and meta-analysis. Eur J Gastroenterol Hepatol. 2018;30(3):329-336. https://doi.org/10.1097/meg. 0000000000001057. 26. Bajaj JS, Tandon P, O’Leary JG, et al. The impact of albumin use on resolution of hyponatremia in hospitalized patients with cirrhosis. Am J Gastroenterol. 2018;113:339-1344. https://doi.org/10.1038/s41395-018-0119-3. 27. Praharaj D, Taneja S, Duseja A, Chawla YK, Dhiman RK. Randomized control trial of rifaximin and norfloxacin in primary and secondary prophylaxis of spontaneous bacterial peritonitis (SBP) in cirrhotic patients. J Clini Exp Hepatol. 2017;7:S71. https://doi.org/10.1016/j.jceh. 2017.05.133. 28. Khan RS, Houlihan DD, Newsome PN. Investigation of jaundice. Medicine. 2015;43(10):573-576. https://doi.org10.1016/j.mpmed.2015.07. 009. 29. Berger L, Garcia Popov A, Berger B. Case report: Relieving the itch of cholestasis with corticosteroids in palliative care. J Palliative Med. 2015;18(11):913-914. https://doi.org/10.1089/jpm.2015.0304. 30. Prabhakar D, Peterson EL, Hu Y, et al. Dermatologic conditions and risk of suicide: a case-control study. Psychosomatics. 2018;59(1):58-61. https://doi. org/10.1016/j.psym.2017.08.001. 31. Carrion AF, Rosen JD, Levy C. Understanding and treating pruritus in primary biliary cholangitis. Clin Liver Dis. 2018;22(3):517-532. https://doi.org/10.1016/j. cld.2018.03.005. 32. Ströhle A, Hadji P, Hahn A. Calcium and bone health—goodbye, calcium supplements? Climacteric. 2015;18(5):702-714. https://doi.org/10.3109/ 13697137.2015.1016419.
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33. Musso CG, Juarez R, Glassock RJ. Water, electrolyte, acidebase, and trace elements alterations in cirrhotic patients. Int Urol Nephrol. 2017;50(1):81-89. https://doi.org/10.1007/s11255-017-1614-y. 34. Paternostro R, Wagner D, Reiberger T, et al. Low 25-OH-vitamin D levels reflect hepatic dysfunction and are associated with mortality in patients with liver cirrhosis. Wien Klin Wochenschr. 2016;129(1-2):8-15. https://doi.org/10. 1007/s00508-016-1127-1. 35. Konstantakis C, Tselekouni P, Kalafateli M, Triantos C. Vitamin D deficiency in patients with liver cirrhosis. Ann Gastroenterol. 2016;29(3):297-306. https:// doi.org10.20524/aog.2016.0037. 36. AK, Jha SK, Kumar A, Dayal VM, Jha SK. Effect of replenishment of vitamin D on survival in patients with decompensated liver cirrhosis: a prospective study. World J Gastrointest Pathophysiol. 2017;8(3):133. https://doi.org/10. 4291/wjgp.v8.i3.133. 37. Vilstrup H, Amodio P, Bajaj K, et al. Hepatic encephalopathy in chronic liver disease: 2014 practice guideline by the European Association for the Study of the Liver and the American Association for the Study of Liver Diseases. J Hepatol. 2014;61(3):642-659. https://doi.org10.1016/j.jhep. 2014.05.042. 38. Fitzpatrick S, Domingo HDA, Finke SM. The care of the decompensated cirrhotic patient. J Nurse Pract. 2017;13(4):256-263. https://doi.org10.1016/j. nurpra.2016.11.026. 39. Kimer N, Krag A, Møller S, Bendtsen F, Gluud LL. Systematic review with meta-analysis: the effects of rifaximin in hepatic encephalopathy. Aliment Pharmacol Ther. 2014;40(2):123-132. https://doi.org/10.1111/apt.12803. 40. Deutsch M, Koskinas J. Antiplatelets and antithrombotics in patients with liver insufficiency: from pathophysiology to clinical practice. Curr Pharm Design. 2017;23(9):1346-1353. https://doi.org/10.2174/ 1381612822666161205113629. 41. Shah N, Caldwell S. Hemostatic abnormalities in patients with liver disease. UpToDate. 2017. Retrieved from https://www.uptodate.com/contents/ hemostatic-abnormalities-in-patients-with-liver-disease. 42. Ge PS, Runyon BA. The changing role of beta-blocker therapy in patients with cirrhosis. J Hepatol. 2014;60(3):643-653. https://doi.org10.1016/j.jhep.2013.09. 016.
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43. Garcia-Tsao G, Bosch J. Varices and variceal hemorrhage in cirrhosis: a new view of an old problem. Clin Gastroenterol Hepatol. 2015;13(12):2109-2117. https://doi.org/10.1016/j.cgh.2015.07.012. 44. Villanueva C, Albillos A, Genescà J, et al. Development of hyperdynamic circulation and response to b-blockers in compensated cirrhosis with portal hypertension. Hepatology. 2016;63(1):197-206. https://doi.org/10.1002/hep. 28264.
Mohamed Toufic El Hussein, PhD, NP, is an associate professor in the School of Nursing and Midwifery, Faculty of Health, Community & Education, Mount Royal University, Calgary, AB, Canada. He is available at [email protected]. James A. Rankin, PhD, ACNP, is a professor and acute care nurse practitioner at the University of Calgary/Alberta Health Services, Calgary, Alberta, Canada. Karen Lynn Then, PhD, NP, is a professor and acute care nurse practitioner at the University of Calgary/Alberta Health Services, Calgary, Alberta, Canada. In compliance with national ethical guidelines, the authors report no relationships with business or industry that would pose a conflict of interest. 1555-4155/18/$ see front matter © 2018 Elsevier Inc. All rights reserved. https://doi.org/10.1016/j.nurpra.2018.08.032
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