PULMONARY COMPLICATIONS IN CIRRHOSIS.pptx

Presentation

1. PULMONARY COMPLICATIONS IN CIRRHOSIS Dr.P . Arun kumar Senior resident

2. INTRODUCTION

3. PULMONARY COMPLICATIONS 1)Hepatic hydrothorax 2)Spontaneous bacterial empyema 3)Hepato-pulmonary syndrome 4)Porto-pulmonary hypertension

4. Hepatic hydrothorax

5. Recent analysis showed presence of hepatic hydrothorax associated with median survival of 8-12 months PATHOGENESIS : Most favored hypothesis is transdiaphragmatic shift of fluid from peritoneal into the pleural cavity via diaphragmatic defects Defects can be microscopic or macroscopic, but mostly in right hemidiaphragm

6. In a study of 1038 patients with advanced cirrhosis – 5% had HH -mostly right sided -70% -left sided being 12% and -bilateral 18%. Isolated HH can also present without ascites Ascites coexistent in 80% of cases with HH and is not required for diagnosis.

7. Clinical features Pleural effusion can have severe symptoms like -SOB(at rest 34% and increased on exertion 7%) -cough(non-productive 22%) -pleuritic chest pain 8% and -hypoxemia 7% with as little as 500ml of fluid. Patient can have signs of ascites like abdominal distension and palmar erythema It can be an incidental finding in asymptomatic patient rarely.

8. Less common presentations include -Acute hydrothorax with severe dyspnea and hypotension -Spontaneous bacterial empyema(SBEM)

9. Diagnosis Thoracocentesis and fluid testing Cell count and differential count, Gram stain, Culture and sensitivity Protein, albumin, LDH and bilirubin concentrations Pleural fluid PH Others in special cases -Triglyceride levels(chylothorax) -PCR for Mycobacterium(TB) -Amylase for Pancreatitis -Cytology( malignancy

10. Thoracocentesis complications very scarce Pneumothorax <5%, bleeding <1%, vasovagal reactions <1% Further decreased by USG guided approach Prophylactic blood product substitution like platelet, FFP etc., given only when patient INR >3 or platelet <25000/mm 3 In doubtful cases of hepatic hydrothorax intraperitoneal injection of 99mTc-sulphur colloid or 99mTc- human serum albumin may be helpful as they migrate from peritoneal cavity to pleural space.

11. Treatment Treatment mainly based on similar principles of ascites treatment -Sodium restriction -Diuretics -Large volume paracentesis -Thoracic paracentesis considered only if symptoms persist due to high complication risk -Due to risk of re-expansion pulmonary edema ,pleural paracentesis fluid should not exceed 1.5-2 L/puncture and albumin substituted at 6-8g albumin per litre

12. Sodium restriction- Patient should consume no more than 88Meq of sodium per day Sodium restriction alone will be helpful only in patient who excrete urinary sodium >78 Meq per day Patient should also avoid NSAID intake Diuretics- Patients should be started on Furosemide 40mg and spironolactone 100mg daily If no response -dose is increased every 3-5 days by doubling dose to maximum of 160mg of furosemide and 400mg of spironolactone. Refractory hydrothorax -if patient have persistent hydrothorax despite of sodium restriction and diuretic therapy or who have diuretic related complications – 20 to 25 % patients have refractory hydrothorax

13. Treatment of Refractory hepatic hydrothorax Repeated thoracenteses TIPS placement Pleurodesis Surgical repair of defects in diaphragm Definitive treatment is liver transplantation Continuous transcutaneous thoracic drainage is not recommended as massive protein and electrolytes depletion, risk of infection, renal failure and bleeding Also associated with high mortality compared to recurrent thoracentesis.

14. SPONTANEOUS BACTERIAL EMPYEMA

15. Risk factors -Poor liver function -Low total protein -Low albumin concentrations in serum and/or pleural fluid, and -Low C3 complement in pleural fluid Mortality rate is 20-38% Organisms associated with SBEM frequently include E.coli, Klebsiella, Streptococcus, Pseudomonas or Enterococcus. Patient with history of frequent hospitalisations have MDRO strains.

16. Cardinal symptom- Fever Other symptoms of decompensated liver disease Diagnostic criteria

17. Treatment

18. In an observational study of 54 patients with SBEM early thoracenteses <24 hours from presentation was associated with low rates of mortality ( 7% Vs 41%) and ICU admission (26% vs 56%) compared to delayed intervention.

19. HEPATO-PULMONARY SYNDROME INTRODUCTION: Hepato-pulmonary syndrome is defined as gas exchange disorder resulting from intrapulmonary vascular dilatation in patients with advanced liver disease, portal hypertension or portosystemic shunting. HPS may also occur in acute liver failure such as ischemic or viral hepatitis and portal vein thrombosis.

20. Etiopathogenesis

21. Pathogenesis

22. Pathophysiology

23. Diagnostic workup

24. Arterial oxygen tension (PaO2) Classification of severity <50mmHg Very severe >/= 50 PaO2 < 60mmHg Severe >/=60 PaO2 <80mmhg Moderate >/=80mmhg Mild

25. Contrast Echo cardiography is the most sensitive test It uses agitated normal saline ( (shaken 0.9% saline solution to produce sonographically visible microbubbles > 10 µm in diameter ) and injected IV from peripheral line -In case of intra cardiac shunt – saline bubbles are seen in left ventricles after 1-3 cardiac cycles -In case of Intra pulmonary shunts- Saline bubbles seen in left ventricles after 3-6 cardiac cycles

26. Lung perfusion scintigraphy uses 99m-Technetium-macroaggregated human albumin (MAA) (20–50 µm size), which can only cross pulmonary circulation via a right-left shunt -An increased shunt fraction of > 6% supports evidence that HPS is the major contributor to hypoxemia. Shunt fractions of > 20% indicate very severe HPS (PaO2 < 50 mmHg) and associated with high mortality

27. Contrast pulmonary angiography identifies three angiographic patterns 1)The type 1 minimal pattern was characterized by normal to finely diffuse, spidery abnormalities. It was associated with severe hypoxemia, orthodeoxia, and a good response to 100 percent inspired oxygen. 2)The type 1 advanced pattern which evolves from the type 1 minimal pattern. It was characterized by a diffuse spongy or blotchy angiographic appearance. It was also associated with severe hypoxemia and orthodeoxia but may be less responsive to 100 percent oxygen. 3)The type 2 discrete pattern was characterized by localized, visible arteriovenous communications and was associated with a poor response to supplemental oxygen.

28. Chest computed tomography — High resolution computed tomography (HRCT) of the chest may reveal two characteristic findings of IPVDs, -dilated peripheral pulmonary vessels and -increased pulmonary artery to bronchus ratios.

29. Treatment

30. Liver transplantation

31. Investigational therapies Pentoxifylline , a tumor necrosis factor-alpha inhibitor, vasodilator with anti-angiogenesis, showed variable results in oxygenation improvement in HPS Early-stage HPS patients seem to have a favourable outcome, while patients with advanced-stage HPS had unimproved oxygenation and difficulty tolerating pentoxifylline due to gastrointestinal adverse effects Garlic, has allicin which is a potent vasodilator and anti-angiogenesis. It shows significant improvement in gas exchange in small studies, which include one randomized controlled trial.

32. Methylene blue causes vasoconstriction by inhibiting NO and may also decrease angiogenesis. It has shown some benefits in improving oxygenation; however, no randomized clinical trial is available to support its use Sorafenib is a tyrosine kinase inhibitor that can reduce angiogenesis. It significantly decreased alveolar-arterial oxygen gradient in rat model but failed to show benefit in patients with HPS in a randomized-controlled trial. Octreotide, a somatostatin analogue that can inhibit angiogenesis, also showed no benefit in HPS patients in few studies Mycophenolate mofetil only showed benefit in one case report.

33. Norfloxacin decreases bacterial translocation and reveals benefit in an animal study and a human case report but not in a randomized controlled trial Other medications including iloprost (vasodilator), paroxetine (NO synthase inhibitor ), almitrine bismesylate (pulmonary vasoconstrictor) have been tried without any clear benefit. Letrozole is undergoing an ongoing phase two trial. TIPS has shown some benefit in some small prospective study but limited data available Embolization of Pulmonary vasodilation have shown improvement in oxygen. But more data is required

34. PORTO-PULMONARY HYPERTENSION

35. PATHOGENESIS 1)Imbalance of vasoconstrictive and vasodilatory mediators due to impaired liver metabolization, 2) Hyperdynamic pulmonary circulation with increased sheer stress on the pulmonary vascular wall, 3) Increased local inflammation due to elevated cytokine levels associated with the cirrhotic liver, 4) Thromboembolisms that originated from the portal venous system 5) Genetic predisposition. A remodeling process of the pulmonary vasculature leads to increased pulmonary vascular resistance. Ultimately, this conditions an increased afterload and, in the long run, right-sided heart failure

36. Histopathological picture characterized by -media hypertrophy, -remodeling processes of the pulmonary artery’s lamina muscularis, and -in situ thrombosis. These changes go along with a dysregulation of endogenous vaso regulators -increased endothelin-1 and -reduced prostacyclin synthase from pulmonary endothelial cells, -proliferation of smooth muscle cells, -endothelial activation, and platelet aggregation

37. CLINICAL FEATURES

38. DIAGNOSIS Physical examination -an accentuated and split second heart sound, -right ventricular heave, -right-sided S3 gallop, -jugular venous distention, and -leg oedema may hint at PPHT. Electrocardiographic abnormalities include -right atrial enlargement, -right ventricular hypertrophy, -right axis deviation, and/or right bundle branch block. Radiologically -a prominent main pulmonary artery (hilar enlargement) or -cardiomegaly may be found

39. Portopulmonary hypertension. Chest radiograph of a case of portopulmonary hypertension in a patient with cirrhosis showing dilated central pulmonary arteries and pruning of peripheral pulmonary vessels suggestive of pulmonary arterial hypertension.

40. Gold standard for diagnosis of PPHT is right heart catheterisation(RHC) The following criteria are considered diagnostic for PPHT: Elevated mean pulmonary artery pressure (MPAP) > 25 mmHg at rest, Normal or low pulmonary artery wedge pressure (PAWP) ≤ 15 mmHg at rest, Elevated peripheral vascular resistance (PVR) > 240 dyn-sec-cm-5 and transpulmonary gradient (TPG) > 12 mmHg.

41. Doppler echocardiography correlates with the mPAP measured by RHC. It is used as a screening test, because a RVSP > 30 mmHg in Doppler echocardiography has a negative predictive value of 100%, whereas its positive predictive value is 59%. Based on the mean values of pulmonary artery pressure, PPHT is classified as PULMONARY ARTERY PRESSURE SEVERITY MPAP 25–35 mmHg MILD MPAP 35–45 mmHg MODERATE MPAP ≥ 45 mmHg SEVERE

42. TREATMENT

43. Prostacyclin pathway agonists- - Epoprostenol requires complicated IV administration, but newer agents ( iloprost , treprostinil ) are easier to administer. -In addition, a newer oral prostacyclin receptor agonist ( selexipag ) is available and shows promise as an effective and simple therapy Nitric oxide-cyclic guanosine monophosphate enhancers (phosphodiesterase inhibitors, guanylate cyclase stimulants) are widely used in PAH - A direct cyclic GMP analog ( riociquat ) has also been approved for treatment of PAH and appears to have benefit in POPH In PPHT, phosphodiesterase-5 inhibitors such as sildenafil and tadalafil are commonly used since their metabolism is not affected by liver dysfunction

44. LIVER TRANSPLANTATION

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