1 / 34

Critical Care Journal Reading

Critical Care Journal Reading. Medical management of hepatorenal syndrome Nephrol Dial Transplant (2012) 27: 34–41 doi: 10.1093/ndt/gfr736 Andrew Davenport1, Jawad Ahmad2, Ali Al-Khafaji3, John A. Kellum3, Yuri S. Genyk4 and Mitra K. Nadim5

corin
Download Presentation

Critical Care Journal Reading

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript


  1. Critical Care Journal Reading Medical management of hepatorenal syndrome Nephrol Dial Transplant (2012) 27: 34–41 doi: 10.1093/ndt/gfr736 Andrew Davenport1, Jawad Ahmad2, Ali Al-Khafaji3, John A. Kellum3, Yuri S. Genyk4 and Mitra K. Nadim5 2012/03/26 R2鄭雅婷/ Supervisor 張智翔醫師

  2. Introduction • Hepatorenal syndrome (HRS) is defined as the occurrence of acute kidney injury (AKI) in patients with end-stage liver cirrhosis in the absence of another identifiable cause • Untreated, median survivalis 2 weeks for patients with Type 1 HRS and 4–6 months inpatients with Type 2 HRS

  3. The International Ascites Club

  4. Acute Dialysis QualityInitiative (ADQI) • A consensus conferenceunder the auspices of the Acute Dialysis QualityInitiative (ADQI) was held in 2010 • Appraise the existingevidence • Develop a set of consensus recommendations to standardize care and direct further research

  5. Materials and methods • The ADQI methods comprise • Systemic search for evidence with review and evaluation of the available literature • The establishment of clinical and physiologic outcomes as well as measures to be used for comparison of different treatments • The description of the current practice and the rationale for the use of current techniques • Analysis of areas in which evidence is lacking and future research is required

  6. Materials and methods

  7. Systemic review of the literature • Using key terms relevant to the topic and electronic reference libraries • Focus on human studies • Limited to English language articles • Published between January 1960 and December 2009 • The majority of the work group resources were devoted to review of randomized trials, as these were deemed to be most likely to provide data to support Level 1 recommendations with very high- or high-quality (A or B) evidence

  8. Evaluation of studies • A three-phase approach was used to construct the evidence-based recommendations • A systematic literature review of studies in HRS and AKI in patients with cirrhosis • A comprehensive appraisal of prior studies • Convening an expert panel to synthesize information and develop consensus-based recommendations • Recommendation statements were incorporated • if there was strong literature-based evidence • if the expert panel voted that the recommendation was appropriate

  9. Grading evidence and recommendations

  10. ADQI process

  11. Result General management strategies

  12. Prevention of HRS • Patients with hypotensive may have a reduced cortisol response (hepatoadrenal syndrome) and thus covert hypoadrenalism should be considered and treated appropriately to improve response not only to vasopressors but also survival • Drugs reported to precipitate HRS in patients with cirrhosis should be avoided • Radiocontrast media have not been established as causing AKI in cirrhotics

  13. Drugs reported to precipitate HRS in patients with cirrhosis

  14. Antibiotic prophylaxis to reduce SBP • Norfloxacin • Reduction in SBP (7 versus 61%) • Rreduction in the incidence of HRS (28 versus 41%) • Oxypentifyllin • A tumor necrosis factor-a antagonist • Reduced complications in patients with advanced cirrhosis, including renal dysfunction • Albumin infusions have been reported to decrease the incidence of HRS in patient with SBP

  15. Recommendations for clinical practice • Type 1 HRS patients should be closely monitored and precipitating factors including bacterial infection should be actively sought and treated (not graded) • Drugs reducing renal perfusion or directly causing nephrotoxicity should be avoided (1C) • Exposure to contrast should be minimized to reduce contrastinduced kidney injury (1D)

  16. Assesment of intravascular volumn in patient with cirrhosis • Intravascular volume expansion, which is often necessary to treat HRS, can potentially lead to worsening of ascites, pleural effusion or heart failure • Assessment of intravascular volume in HRS is difficult as the standard static hemodynamics measurements of CVP and PCWP are not reliable markers of circulatory • An infusion of 20% albumin significantly increasing central blood volume and cardiac index, without changes in CVP • The response to a fluid challenge in cirrhotics is likely to be abnormal, as any fluid bolus which initially expands the intravascular space, will subsequently expand the ‘third space’

  17. Recommendations for clinical practice • Excessive administration of fluids should be avoided to prevent volume overload due to the presence of kidney injury and development or progression of dilutional hyponatremia (1D). • Traditional methods in predicting volum responsiveness and should not be relied on (1C).

  18. Recommendation for future research • Prospective studies, specifically of volume assessment with hemodynamic monitoring tools in patients with HRS

  19. Fluid resuscitation in HRS • In advanced liver disease, volume expansion does not always resolve hypotension, most likely due to the increased vascular compliance in cirrhotics • The choice of intravenous fluids used in cirrhotics remains controversial • Volume expansion with albumin has been shown to reduce plasma renin, suggesting an improvement in the effective circulating volume • In randomized controlled clinical trials, albumin infusions reduced both the incidence of HRS and mortality

  20. Fluid resuscitation in HRS • Studies have shown that the use of vasopressors with albumin improves renal function and mortality compared to vasopressor alone • In one randomized study in patients with SBP, albumin significantly • Increased mean arterial pressure (MAP) and suppressed plasma renin activity, compared to hetastarch • Serum nitrates increased with hetastarch but not with albumin • Less neurohumeral activation compared to other colloids • Less volume expanders post-large-volume paracentesis • Plasma von Willebrand-related antigen fell significantly

  21. Recommendations for clinical practice • Intravenous administration of albumin (initially 1 g of albumin/kg of body weight, up to a maximum of 100 g, followed by 20–40 g/day) in combination with vasopressor therapy (1A) • For up to 14 days (2D)

  22. Paracentesis • AKI due to abdominal compartment syndrome is well recognized with intra-abdominal pressures (IAP) typically >18 mmHg • Uncontrolled studies have reported an improvement in renal function in patients with HRS following paracentesis for raised IAP

  23. Recommendation for future research • Prospective studies are required to investigate the effect of reducing IAP on renal function in patients at risk of developing or with established HRS

  24. Pharmacological treatment of HRS • Splanchnic vasodilatation plays a key role in the pathogenesis of HRS • The prospective trials focused on treatment if type 1 HRS with vasocontrictiors reported an improvement in renal function (but not a survival benefit)

  25. Vasopressin • Activation V1 receptor leads to vascular smooth muscle contraction • High density of V1 receptors in the splanchnic bed make this vasculature especially responsive to vasopressin

  26. Terlipressin • Distinctive vasopressin analog • Preferential effects on the V1 receptor • Lower rate of ischemic complications • The most widely studied agent for Type 1 HRS • Several small studies have demonstrated that terlipressin significantly decreases plasma renin and aldosterone, with an improvement in glomerular filtration rate (GFR) in patients with type 1 HRS • The importance of albumin infusion to terlipressin therapy was emphasized in a prospective study of predominantly Type 1 HRS

  27. Three randomized prospective trials • Terlipressin dosages ranged from 2 to 12 mg/day in divided doses and 20–40 g/day of albumin. • The duration of therapy is usually ≤ 2 weeks • The aim is to improve renal function sufficiently to decrease the Scr <1.5 mg/dL (complete response) • Renal function was improved in Type 1 HRS • There are no studies on how best to discontinue terlipressin therapy, and whether this affects HRS recurrence • Studies have focused on changes in Scr rather than titrating terlipressin to achieve a target MAP • In most studies, there were no overall survival benefits

  28. Trials for Terlipressin • More recent studies have focused on early predictors of response with a baseline serum bilirubin (<10 mg/dL) and an increase in MAP of 5 mmHg by Day 3 predicting response • Terlipressin may be beneficial in cirrhotics with ascites and renal impairment before they fulfill the diagnostic criteria for HRS, by decreasing plasma renin and norepinephrine and increasing GFR and natriuresis • Patients with additional comorbidities such as ischemic heart and peripheral vascular disease have typically been excluded from studies

  29. Norepinephrine (noradrenaline) • A catecholamine but its alpha-adrenergic activity • Potent vasoconstrictor of both the venous and arterial vasculature • A pilot study Type 1 HRS used norepinephrine at a dose titrated to achieve an increase in MAP of 10 mmHg or an increase in 4-h urine output to >200 mL • Reversal of HRS occurred in 83%, with improvement in urine output, sodium excretion, serum sodium concentration, creatinine clearance, MAP, plasma renin activity and aldosterone

  30. Octreotide and midodrine • Oral midodrine, an alpha-adrenergic receptor agonist • Vascular smooth muscle vasoconstriction • Subcutaneous octreotide : long-acting somatostatin analogue which is used reduce portal hypertension after variceal hemorrhage • Early studies in Type 2 HRS demonstrated no improvement in renal function with midodrine or octreotide • The combination of thrice daily midodrine 7.5–12.5 mg and octreotide 100–200 μg, and albumin, improved renal plasma flow, GFR and urinary sodium extraction in Type 1 HRS after 3 weeks of treatment

  31. Other agents • Ornipressin, a vaspressin analogue • High rate of ischemic complications (including ischemic colitis and tongue ischemia) requiring ornipressin withdrawal • N-acetyl cysteine reported to help reverse HRS in case reports, but awaits confirmation • Oxypentifylline, used in alcoholic hepatitis, has been reported to reduce the incidence of HRS, but has not been shown to improve renal function in established HRS

  32. Recommendations for clinical practice • In type 1 HRS, patients optimally resuscitated with albumin (initially 1 g of albumin/kg of body weight for 2 days, up to a maximum of 100 g/day, followed by 20–40 g/day) in combination with a vasoconstrictor (1A), preferentially terlipressin (2C) • Therapy should be discontinued after 14 days in non-responders and only continued thereafter in partial responders while awaiting the outcome of salvage techniques (2D).

  33. Recommendation for future research • Prospective trials are required to determine the optimum mode of delivery of terlipressin (bolus versus infusion). • Comparative trials of vasoconstrictors are required to determine the merits of vasopressin analogs against norepinephrine

  34. Conclusions • Although the introduction of terlipressin and albumin has improved the outlook for patients with HRS, only ~50% of patients respond to therapy • Questions remain • Whether earlier introduction of this therapy would help prevent the development of HRS • In patients with established HRS how best to administer terlipressin and if targeting vasoconstrictor dosage to an absolute or relative increase in MAP improves response • The effects of changes in IAP on renal function have not been explored

More Related