1. Intensive care conference: management of acid-base disorders with CRRT -- 2011 International Society of Nephrology 主講人 : R2 顏介立

2. Introduction 1. acid-base homeostasis  challenge in ICU 2. Focus on CRRT (Continuous renal replacement therapies ) in critical patient with AKI 3. hypercapnic acidosis and lactic acidosis for example

3. CRRT (Continuous renal replacement therapies ) - called "go slow dialysis” - The major advantage of continuous therapy is the slower rate of solute or fluid removal per unit of time - CVVHD (Continuous veno-venous hemodialysis ) - CVVHF (Continuous veno-venous hemofiltration ) - CVVHDF

4. CRRT (Continuous renal replacement therapies )

5. Hypercapnic acidosis 1. Cause - Increase CO2 production or decrease CO2 elimination 2. Physiological compensatory: lung: hypercapnia stimulate cental and paripheral chemoreceptors=>increase ventilation

6. Hypercapnic acidosis 2. Physiological compensatory : kidney: 3-5 days (in animal model) ** but this mechanism is limited in AKI patient

7. Hypercapnic acidosis 3. Management - ALI/ARDS treatment: CO2 retention permission =>low tidal volume(4-6ml/kg) and low pressure(<30) =>maintain adequate oxygenation =>PaCO2=66.5mmhg/ PH decrease to 7.2 - Acidosis would “well tolerated” if fair tissue perfusion and oxygen

8. Hypercapnic acidosis 3. Management - Hypercapnic acidosis controversies: Advantage: improve arterial and tissue oxygenation, reduce oxidative stress, anti-inflammatory effect Disadvantage: vasodilating effect, increase capillary permeability (may worsen brain edema) =>ICH may cause myocardial depression, pulmonary hypertension Conclusion: patient with advanced age and multiple comorbidities, lung-protective stragegies may disadvantage

9. Hypercapnic acidosis 3. Management sodium bicarbonate : - Worsen exisiting hypercapnia - Worsen heart failure due to volume expansion, hyperosmolality, decrease ionized calcium plasma concentration - Hypercapnic acidosis treat by sodium bicarbonate is not recommended unless metabolic acidosis co- exist

10. Hypercapnic acidosis 3. Management -Intermittent hemodialysis: rapid flux of bicarbonate => excess CO2=> required hyperventilation -CRRT: much slower buffer delivery=> correct combined respiratory and metabolic acidosis by CRRT in case reports.

11. Hypercapnic acidosis 3. Management - Convective hemofiltration: use hemofiltration with replacement fluid contain NaOH can remove half of CO2 production =>50% reduction in minute ventilation and keep PaCO2 level 35-38 with stable blood PH - CVVHF may an effective adjunctive treatment for acidosis in respiratory failure patient => avoid intubation and ventilator induced ALI or infection

12. Lactic acidosis 1. pathophysiology: - Pyruvate: precursor of lactate PDH

13. Lactic acidosis 2. Classification of lactic acidosis: - Type A : inadequate oxygen supply - Type B: dysregulation of metabolism rather than hypoxia B1: liver disease, malignancy B2: drug induced: metformin, aspirin, propofol…… B3: congenital - Sepsis induced lactic acidosis

14. Lactic acidosis 3. Clinical application of lactate: - Lactate acidosis is related to high mortality - Lactate is a prognosis indicator surviving sepsis campaign regard lactate level>4 mmol/L need aggressive treatment protocols - Treat underlying disease

15. Lactic acidosis 4. Treatment of lactic acidosis: - Treatment underlying disease - Sodium bicarbonate: may worsen oxygen delivery, increase lactate production (especially when hypoxia=>induce glycolysis), decrease portal vein flow - The surviving sepsis campaign recommended hold sodium bicarbonate unless ph<7.15 -two randonmized trials

16. Lactic acidosis 4. Treatment of lactic acidosis - CRRT Type A lactic acidosis: small observational studies showed efficient management of severe type A lactic acidosis=> CRRT vs sodium bicarbonate infusion

17. Lactic acidosis 4. Treatment of lactic acidosis - CRRT Drug-induced lactic acidosis: metformin - shock and overdose @ increase intestinal lactic acid production, impaired gluconeogensis, glycogenolysis, mitocondrial respiration and phophorylation=>mortality rate>30% @metformin is sliminated by kidney and highly water soluble

18. Lactic acidosis 4. Treatment of lactic acidosis - CRRT -Drug induced lactic acidosis Hemodialysis and CRRT=> Correct acidosis and remove metformin from plasma -NRTI-induced lactic acidosis -Summary: CRRT are useful in uncontrollable acidemia with multiple organ failure, and removal causative toxin

19. Anticoagulation - heparin: Heparin is the most commonly utilized anticoagulant @ risk of systemic bleeding and heparin-induced thrombocytopenia

20. Anticoagulation Citrate: - chelating ionized calcium=> anticoagulation @decrease risk of systemic bleeding @systemic calcium infusion - Citrate=>bicarbonate (carbonic anhydrase) @liver, skeletal muscle, kidney (high mitochondria) - Citrate toxicity=> in liver failure patient @ metabolic acidosis=> because bicarbonate loss and citrate can’t metabolize bicarbonate @ ca2+ decrease but total plasma calcium increase

21. Conclusion - Hypercapnic acidosis and lactic acidosis - Bicarbonate infusion vs addition bicarbonate during CRRT - Need further prospective controlled study

22. Thanks for your attention ~~ Any question?