Ultrafiltration for Cirrhotic Patients during Cardiopulmonary Bypass: Egyptian Experience. Dr. Mohamed R. El–Tahan, M.D.

IntroductionIntroduction Cardiac Surgery & Cirrhosis History of UF Principle of UF Types of UF MUFMUFCUFCUFDUFDUF UF & Cirrhosis Our Study

IntroductionIntroduction Cardiac Surgery & Cirrhosis History of UF Principle of UF Types of UF MUFMUFCUFCUFDUFDUF UF & Cirrhosis Our Study

IntroductionIntroduction Cardiac Surgery & Cirrhosis History of UF Principle of UF Types of UF MUFMUFCUFCUFDUFDUF UF & Cirrhosis Our Study

IntroductionIntroduction Cardiac Surgery & Cirrhosis History of UF Principle of UF Types of UF MUFMUFCUFCUFDUFDUF UF & Cirrhosis Our Study

IntroductionIntroduction Cardiac Surgery & Cirrhosis History of UF Principle of UF Types of UF MUFMUFCUFCUFDUFDUF UF & Cirrhosis Our Study

IntroductionIntroduction Cardiac Surgery & Cirrhosis History of UF Principle of UF Types of UF MUFMUFCUFCUFDUFDUF UF & Cirrhosis Our Study

IntroductionIntroduction Cardiac Surgery & Cirrhosis History of UF Principle of UF Types of UF MUFMUFCUFCUFDUFDUF UF & Cirrhosis Our Study

IntroductionIntroduction Cardiac Surgery & Cirrhosis History of UF Principle of UF Types of UF MUFMUFCUFCUFDUFDUF UF & Cirrhosis Our Study

IntroductionIntroduction Cardiac Surgery & Cirrhosis History of UF Principle of UF Types of UF MUFMUFCUFCUFDUFDUF UF & Cirrhosis Our Study

IntroductionIntroduction Cardiac Surgery & Cirrhosis History of UF Principle of UF Types of UF MUFMUFCUFCUFDUFDUF UF & Cirrhosis Our Study

The hill of schistosomiasis in the Nile Delta, Lower and Upper Egypt Egypt is the Gift of the Nile

IntroductionIntroduction Cardiac Surgery & Cirrhosis History of UF Principle of UF Types of UF MUFMUFCUFCUFDUFDUF UF & Cirrhosis Our Study

Egypt has possibly the highest HCV prevalence worldwide (10%–20%) and is the leading cause of chronic liver disease and hepatocellular carcinoma. IntroductionIntroduction Cardiac Surgery & Cirrhosis History of UF Principle of UF Types of UF MUFMUFCUFCUFDUFDUF UF & Cirrhosis Our Study

IntroductionIntroduction Cardiac Surgery & Cirrhosis History of UF Principle of UF Types of UF MUFMUFCUFCUFDUFDUF UF & Cirrhosis Our Study

IntroductionIntroduction Cardiac Surgery & Cirrhosis History of UF Principle of UF Types of UF MUFMUFCUFCUFDUFDUF UF & Cirrhosis Our Study Patients with mild or moderate cirrhosis have prolonged hospitalization and high mortality and morbidity rates after cardiac surgery using cardiopulmonary bypass.

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Worsening postoperative function of vital organs may be attributed to the SIRS and capillary leak syndrome caused by CPB. IntroductionIntroduction Cardiac Surgery & Cirrhosis History of UF Principle of UF Types of UF MUFMUFCUFCUFDUFDUF UF & Cirrhosis Our Study

IntroductionIntroduction Cardiac Surgery & Cirrhosis History of UF Principle of UF Types of UF MUFMUFCUFCUFDUFDUF UF & Cirrhosis Our Study

The concept of removing excess fluid from the intravascular space of patients in renal failure by the filtration of blood through an ultraporous membrane dates back to Brull L. Realization de l'ultrafiltration in vivo. C R Soc Biol (Paris) 1928;99:1605–1608. IntroductionIntroduction Cardiac Surgery & Cirrhosis History of UF Principle of UF Types of UF MUFMUFCUFCUFDUFDUF UF & Cirrhosis Our Study

Unfortunately, the first clinical applications of ultrafiltration in patients with renal failure did not occur until the IntroductionIntroduction Cardiac Surgery & Cirrhosis History of UF Principle of UF Types of UF MUFMUFCUFCUFDUFDUF UF & Cirrhosis Our Study

During the 1970s, Lee West Henderson was the first who used the UF during open heart surgery. IntroductionIntroduction Cardiac Surgery & Cirrhosis History of UF Principle of UF Types of UF MUFMUFCUFCUFDUFDUF UF & Cirrhosis Our Study

IntroductionIntroduction Cardiac Surgery & Cirrhosis History of UF Principle of UF Types of UF MUFMUFCUFCUFDUFDUF UF & Cirrhosis Our Study

Ultrafiltration is the selective separation of plasma water and LMW solutes from the intravascular cellular components and plasma proteins, using a semipermeable membrane filter. IntroductionIntroduction Cardiac Surgery & Cirrhosis History of UF Principle of UF Types of UF MUFMUFCUFCUFDUFDUF UF & Cirrhosis Our Study

IntroductionIntroduction Cardiac Surgery & Cirrhosis History of UF Principle of UF Types of UF MUFMUFCUFCUFDUFDUF UF & Cirrhosis Our Study

UF is being categorized by the timing and technique used in the UF process: IntroductionIntroduction Cardiac Surgery & Cirrhosis History of UF Principle of UF Types of UF MUFMUFCUFCUFDUFDUF UF & Cirrhosis Our Study

Conventional ultrafiltration Conventional ultrafiltration is performed during CPB (usually during the rewarming phase) and the volume removed is based on the volume within the CPB circuit. IntroductionIntroduction Cardiac Surgery & Cirrhosis History of UF Principle of UF Types of UF MUFMUFCUFCUFDUFDUF UF & Cirrhosis Our Study

IntroductionIntroduction Cardiac Surgery & Cirrhosis History of UF Principle of UF Types of UF MUFMUFCUFCUFDUFDUF UF & Cirrhosis Our Study

Modified ultrafiltration Modified ultrafiltration refers to the use of ultrafiltration after the stabilization of the patient’s hemodynamics after CPB. IntroductionIntroduction Cardiac Surgery & Cirrhosis History of UF Principle of UF Types of UF MUFMUFCUFCUFDUFDUF UF & Cirrhosis Our Study

An ultrafilter is placed with the inlet connected to the aortic cannula and the outlet connected to the right atrium via the venous catheter.

Blood flow rate through the filter is maintained at 200 to 300 mL/min to produce an UF rate of 100 to 150 mL/min Infusion rates is adjusted to maintain appropriate CVP or LAP. IntroductionIntroduction Cardiac Surgery & Cirrhosis History of UF Principle of UF Types of UF MUFMUFCUFCUFDUFDUF UF & Cirrhosis Our Study

MUF The MUF removed volume after CPB is 20 to 30 mL/kg. IntroductionIntroduction Cardiac Surgery & Cirrhosis History of UF Principle of UF Types of UF MUFMUFCUFCUFDUFDUF UF & Cirrhosis Our Study

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IntroductionIntroduction Cardiac Surgery & Cirrhosis History of UF Principle of UF Types of UF MUFMUFCUFCUFDUFDUF UF & Cirrhosis Our Study

Continuous ultrafiltration Continuous ultrafiltration ( CUF+MUF) is a technique that using both CUF and MUF during and after the cessation of CPB, respectively. IntroductionIntroduction Cardiac Surgery & Cirrhosis History of UF Principle of UF Types of UF MUFMUFCUFCUFDUFDUF UF & Cirrhosis Our Study

CUF attenuates the inflammatory response, increases hemoglobin conc. and platelets, improves hemodynamics, decreases the need for transfusion, postoperative ventilation and ICU stay. IntroductionIntroduction Cardiac Surgery & Cirrhosis History of UF Principle of UF Types of UF MUFMUFCUFCUFDUFDUF UF & Cirrhosis Our Study

IntroductionIntroduction Cardiac Surgery & Cirrhosis History of UF Principle of UF Types of UF MUFMUFCUFCUFDUFDUF UF & Cirrhosis Our Study

Semi-continuous UF throughout CPB but it is interrupted during weaning from CPB. Allow UF rate = the crystalloid cardioplegia volume + 40–70 mL/kg/hr. IntroductionIntroduction Cardiac Surgery & Cirrhosis History of UF Principle of UF Types of UF MUFMUFCUFCUFDUFDUF UF & Cirrhosis Our Study

Adding small aliquots of crystalloid < 20 mL/kg as necessary to maintain a safe blood level in the venous reservoir. IntroductionIntroduction Cardiac Surgery & Cirrhosis History of UF Principle of UF Types of UF MUFMUFCUFCUFDUFDUF UF & Cirrhosis Our Study

IntroductionIntroduction Cardiac Surgery & Cirrhosis History of UF Principle of UF Types of UF MUFMUFCUFCUFDUFDUF UF & Cirrhosis Our Study

Contributing factors for adverse outcome in cirrhotic patients after CPB include: IntroductionIntroduction Cardiac Surgery & Cirrhosis History of UF Principle of UF Types of UF MUFMUFCUFCUFDUFDUF UF & Cirrhosis Our Study  no pulsatile flow,  hemodilution,  hemolysis,  activation of the inflammatory cascade,  anticoagulation,  hypothermia,  and reduced end-organ perfusion.  no pulsatile flow,  hemodilution,  hemolysis,  activation of the inflammatory cascade,  anticoagulation,  hypothermia,  and reduced end-organ perfusion.

IntroductionIntroduction Cardiac Surgery & Cirrhosis History of UF Principle of UF Types of UF MUFMUFCUFCUFDUFDUF UF & Cirrhosis Our Study

IntroductionIntroduction Cardiac Surgery & Cirrhosis History of UF Principle of UF Types of UF MUFMUFCUFCUFDUFDUF UF & Cirrhosis Our Study

IntroductionIntroduction Cardiac Surgery & Cirrhosis History of UF Principle of UF Types of UF MUFMUFCUFCUFDUFDUF UF & Cirrhosis Our Study

IntroductionIntroduction Cardiac Surgery & Cirrhosis History of UF Principle of UF Types of UF MUFMUFCUFCUFDUFDUF UF & Cirrhosis Our Study

We postulated that CUF + MUF may decrease the need for transfusion and shorten the durations of ventilation and ICU stay in the cirrhotic patients after valve surgery. IntroductionIntroduction Cardiac Surgery & Cirrhosis History of UF Principle of UF Types of UF MUFMUFCUFCUFDUFDUF UF & Cirrhosis Our Study

A priori power analysis indicated that 30 patients in each group would be a sufficiently sample size to detect a 20% reduction in aminotransferase values, with a type-I error of 0.05 and a power of 87%. IntroductionIntroduction Cardiac Surgery & Cirrhosis History of UF Principle of UF Types of UF MUFMUFCUFCUFDUFDUF UF & Cirrhosis Our Study

Sixty cirrhotic ASA II – IV patients (Child-Pugh Grade A–C) scheduled for valvular heart surgery using CPB were studied. IntroductionIntroduction Cardiac Surgery & Cirrhosis History of UF Principle of UF Types of UF MUFMUFCUFCUFDUFDUF UF & Cirrhosis Our Study

Patients with history of IHD, LV dysfunction, cirrhotic cardiomyopathy, thyrotoxicosis, neurological, renal diseases, pregnancy, preoperative circulatory or ventilatory support, or re-do or emergency surgery were excluded. IntroductionIntroduction Cardiac Surgery & Cirrhosis History of UF Principle of UF Types of UF MUFMUFCUFCUFDUFDUF UF & Cirrhosis Our Study

The CUF group (n = 30) conventional ultrafiltration was used. CUF volume of 20 – 30 mL kg -1 was removed during CPB and it was stopped if the venous reservoir level fell low. IntroductionIntroduction Cardiac Surgery & Cirrhosis History of UF Principle of UF Types of UF MUFMUFCUFCUFDUFDUF UF & Cirrhosis Our Study

The CUF+MUF group (n = 30) conventional ultrafiltration was performed during CPB and MUF was performed after termination of CPB. MUF volume of 20 – 30 mL kg -1 was removed after CPB. IntroductionIntroduction Cardiac Surgery & Cirrhosis History of UF Principle of UF Types of UF MUFMUFCUFCUFDUFDUF UF & Cirrhosis Our Study

The target volume for UF removal was: (priming solution + any additional fluid during CPB) – (CUF fluid + UOP during bypass). IntroductionIntroduction Cardiac Surgery & Cirrhosis History of UF Principle of UF Types of UF MUFMUFCUFCUFDUFDUF UF & Cirrhosis Our Study

Perioperative LFTs, haematocrit, platelet count, doses of inotropic support, the time to extubation, the durations of the postoperative ventilation and ICU and hospital stays were recorded. IntroductionIntroduction Cardiac Surgery & Cirrhosis History of UF Principle of UF Types of UF MUFMUFCUFCUFDUFDUF UF & Cirrhosis Our Study

71.3% mortality 52.6% mortality 19.6% mortality 6.0% mortality 1.9% mortality

Un-paired student t- test and Mann-Whitney U test were used as appropriate with repeated measure analysis of variance. IntroductionIntroduction Cardiac Surgery & Cirrhosis History of UF Principle of UF Types of UF MUFMUFCUFCUFDUFDUF UF & Cirrhosis Our Study

The main causes of hepatic cirrhosis were hepatitis C in 47 (78.3%), hepatitis B in 10 (16.7%), and undetermined conditions in 3 (5%). IntroductionIntroduction Cardiac Surgery & Cirrhosis History of UF Principle of UF Types of UF MUFMUFCUFCUFDUFDUF UF & Cirrhosis Our Study

IntroductionIntroduction Cardiac Surgery & Cirrhosis History of UF Principle of UF Types of UF MUFMUFCUFCUFDUFDUF UF & Cirrhosis Our Study CUFCUF + MUF (n=30) Age (years)27.3± ±8.3 Sex (M/F)21 / 30 (70%)18 / 30 (60%) Weight(Kg)67.5± ±9.2 Height(cm)166.5± ±4.3 Child-Pugh Grade A14 (46.7%)11 (36.7%) Grade B13 (43.3%)15 (50%) Grade C3 (10%)4 (13.3%) MELD score20 [21]19 [23] EuroSCORE3.7 [6]3.2 [6] Height(cm)166.5± ±4.3 Types of surgery Aortic valve replacement9 (30%)12 (40%) Mitral valve replacement14 (46.7%)10 (33.4%) Double valve replacement5 (16.6%)4 (13.3%) Triple valve Surgery2 (6.7%)4 (13.3%) CPB time (min)102.4± ±27.3 Aortic clamping time (min)57.5± ±28.8 Table (1): Patients data.

IntroductionIntroduction Cardiac Surgery & Cirrhosis History of UF Principle of UF Types of UF MUFMUFCUFCUFDUFDUF UF & Cirrhosis Our Study CUFCUF + MUFP value (n=30) NTG dose (µg kg -1 min -1 )1.7± ± Epinephrine dose (ng.kg -1.min -1 )97± ± Volume of CUF (mL)1687.5± ± Volume of MUF (mL)1541.4± Time to extubation (hrs)10.3± ± Ventilation time (hrs)8.6± ± Perioperative bleeding (mL)1064± ± PRBCs transfusion (n)4.4± ± ICU length of stay (days)7.6± ± Hospital length of stay (days)18.7± ± Mortality (n(%))2 (6.7%)1 (3.3%) Table (2): Clinical data. Data are mean ± SD and number (%). * P< 0.05 significant compared with CUF group.

IntroductionIntroduction Cardiac Surgery & Cirrhosis History of UF Principle of UF Types of UF MUFMUFCUFCUFDUFDUF UF & Cirrhosis Our Study Figure (1): Haematocrit (%) changes. Data are mean ± SD. * P< 0.05 significant compared with CUF group.

IntroductionIntroduction Cardiac Surgery & Cirrhosis History of UF Principle of UF Types of UF MUFMUFCUFCUFDUFDUF UF & Cirrhosis Our Study Data are mean ± SD. * P< 0.05 significant compared with CUF group. Figure (2): Platelets (10 4 /µmL) changes.

IntroductionIntroduction Cardiac Surgery & Cirrhosis History of UF Principle of UF Types of UF MUFMUFCUFCUFDUFDUF UF & Cirrhosis Our Study GroupPostoperative Baseline12 hDay 1Day 3Day 7 AST (IU/L) CUF 47.2± ± ± ± ±27.94 CUF + MUF 39.9± ±25.64 *84.1±29.14 *90.7±14.74 *53.6±18.92 * ALT (IU/L) CUF 46.7± ± ± ± ±37.81 CUF + MUF 38.5± ±21.54 *82.1±14.91 *96.6±13.64 *59.2±16.50 * ALP (IU/L) CUF 154.9± ± ± ± ± CUF + MUF 161.3± ±74.42*186.4±74.42*166.1±60.53*127.7±54.80 * GGTP (IU/L) CUF 112.9± ± ± ± ±78.61 CUF + MUF 115.8± ±61.80*176.6±56.40*139.8±49.21*121.7±42.84 * Table (3): Liver enzymes changes. Data are mean ± SD. * P< 0.05 significant compared with CUF group.

IntroductionIntroduction Cardiac Surgery & Cirrhosis History of UF Principle of UF Types of UF MUFMUFCUFCUFDUFDUF UF & Cirrhosis Our Study Figure (3): Bilirubin (mg dL -1 ) changes. Data are mean ± SD. * P< 0.05 significant compared with CUF group.

IntroductionIntroduction Cardiac Surgery & Cirrhosis History of UF Principle of UF Types of UF MUFMUFCUFCUFDUFDUF UF & Cirrhosis Our Study Figure (4): Albumin (gm dL -1 ) changes. Data are mean ± SD. * P< 0.05 significant compared with CUF group.

IntroductionIntroduction Cardiac Surgery & Cirrhosis History of UF Principle of UF Types of UF MUFMUFCUFCUFDUFDUF UF & Cirrhosis Our Study Figure (5): Prothrombin time (sec) changes. Data are mean ± SD. * P< 0.05 significant compared with CUF group.

IntroductionIntroduction Cardiac Surgery & Cirrhosis History of UF Principle of UF Types of UF MUFMUFCUFCUFDUFDUF UF & Cirrhosis Our Study CUFCUF + MUF P value (n=30) Coagulopathy4 (13.3%)2 (6.7%)0.770 Pulmonary1 (3.3%)0 (0%)0.814 Renal1 (3.3%)0 (0%)0.556 New onset or worsening of ascites5 (16.7%)3 (10%)0.477 Encephalopathy3 (10%)1 (3.3%)0.442 Wound dehiscence or infection1 (3.3%)2 (6.7%)0.544 Mortality2 (6.7%)1 (3.3%)0.544 Table (4): Perioperative Complications. Data are number (%). * P< 0.05 significant compared with CUF group.

IntroductionIntroduction Cardiac Surgery & Cirrhosis History of UF Principle of UF Types of UF MUFMUFCUFCUFDUFDUF UF & Cirrhosis Our Study

The studied population is quite different from other institutions with the extreme youth of the studied patients (30 years). IntroductionIntroduction Cardiac Surgery & Cirrhosis History of UF Principle of UF Types of UF MUFMUFCUFCUFDUFDUF UF & Cirrhosis Our Study

The small BMI (24-26 kg/m 2 ) of the studied population would have a significant hemodilutional effect from CPB & the use of CUF+MUF might have a greater effect than with a larger size population. IntroductionIntroduction Cardiac Surgery & Cirrhosis History of UF Principle of UF Types of UF MUFMUFCUFCUFDUFDUF UF & Cirrhosis Our Study

We concluded that CUF + MUF reduced postoperative bleeding and transfusions, improved liver function and shortened the hospital stay in cirrhotic patients after valvular heart surgery. IntroductionIntroduction Cardiac Surgery & Cirrhosis History of UF Principle of UF Types of UF MUFMUFCUFCUFDUFDUF UF & Cirrhosis Our Study

IntroductionIntroduction Cardiac Surgery & Cirrhosis History of UF Principle of UF Types of UF MUFMUFCUFCUFDUFDUF UF & Cirrhosis Our Study