Liver replacement therapy with extracorporeal blood purification techniques current knowledge and future directions.

Clinically, it is highly challenging to promote recovery in patients with acute liver failure (ALF) and acute-on-chronic liver failure (ACLF). Despite recent advances in understanding the underlying mechanisms of ALF and ACLF, standard medical therapy remains the primary therapeutic approach. Liver transplantation (LT) is considered the last option, and in several cases, it is the only intervention that can be lifesaving. Unfortunately, this intervention is limited by organ donation shortage or exclusion criteria such that not all patients in need can receive a transplant. Another option is to restore impaired liver function with artificial extracorporeal blood purification systems. The first such systems were developed at the end of the 20th century, providing solutions as bridging therapy, either for liver recovery or LT. They enhance the elimination of metabolites and substances that accumulate due to compromised liver function. In addition, they aid in clearance of molecules released during acute liver decompensation, which can initiate an excessive inflammatory response in these patients causing hepatic encephalopathy, multiple-organ failure, and other complications of liver failure. As compared to renal replacement therapies, we have been unsuccessful in using artificial extracorporeal blood purification systems to completely replace liver function despite the outstanding technological evolution of these systems. Extracting middle to high-molecular-weight and hydrophobic/protein-bound molecules remains extremely challenging. The majority of the currently available systems include a combination of methods that cleanse different ranges and types of molecules and toxins. Furthermore, conventional methods such as plasma exchange are being re-evaluated, and novel adsorption filters are increasingly being used for liver indications. These strategies are very promising for the treatment of liver failure. Nevertheless, the best method, system, or device has not been developed yet, and its probability of getting developed in the near future is also low. Furthermore, little is known about the effects of liver support systems on the overall and transplant-free survival of these patients, and further investigation using randomized controlled trials and meta-analyses is needed. This review presents the most popular extracorporeal blood purification techniques for liver replacement therapy. It focuses on general principles of their function, and on evidence regarding their effectiveness in detoxification and in supporting patients with ALF and ACLF. In addition, we have outlined the basic advantages and disadvantages of each system.

The use of mean circulatory filling pressure analogue for monitoring hemodynamic coherence: A post-hoc analysis of the SPARSE data and proof-of-concept study.

BACKGROUND: Dissociation between macrocirculation and microcirculation is often observed in surgical patients. OBJECTIVE: To test the hypothesis that the analogue of mean circulatory filling pressure (Pmca) can monitor hemodynamic coherence during major non-cardiac surgery. METHODS: In this post-hoc analysis and proof-of-concept study, we used the central venous pressure (CVP), mean arterial pressure (MAP), and cardiac output (CO) to calculate Pmca. Efficiency of the heart (Eh), arterial resistance (Rart), effective arterial elastance (Ea), venous compartment resistance (Rven), oxygen delivery (DO2), and oxygen extraction ratio (O2ER) were also calculated. Sublingual microcirculation was assessed using SDF + imaging, and the De Backer score, Consensus Proportion of Perfused Vessels (Consensus PPV), and Consensus PPV (small) were determined. RESULTS: Thirteen patients were included, with a median age of 66 years. Median Pmca was 16 (14.9-18) mmHg and was positively associated with CO [p < 0.001; a 1 mmHg increase in Pmca increases CO by 0.73 L  min-1 (p < 0.001)], Eh (p < 0.001), Rart (p = 0.01), Ea (p = 0.03), Rven (p = 0.005), DO2 (p = 0.03), and O2ER (p = 0.02). A significant correlation was observed between Pmca and Consensus PPV (p = 0.02), but not with De Backer Score (p = 0.34) or Consensus PPV (small) (p = 0.1). CONCLUSION: Significant associations exist between Pmca and several hemodynamic and metabolic variables including Consensus PPV. Adequately powered studies should determine whether Pmca can provide real-time information on hemodynamic coherence.

Salutary Effects of the PULVAD, a Novel Implantable Counterpulsation Assist Device, on Cardiac Mechanoenergetics.

The Pressure Unloading Left Ventricular Assist Vevice (PULVAD) is a novel implantable counterpulsation LVAD, designed to provide ventricular unloading with augmentation of LV performance and retention of pulsatility. We assessed the effects of the PULVAD on hemodynamics and LV mechanoenergetics in seven farm pigs with acute ischemic heart failure. The PULVAD was implanted in the thorax and was connected to the ascending aorta. The PULVAD was pneumatically driven by a standard intra-aortic balloon pump console and was electrocardiogram-synchronized to provide LV pressure unloading along with diastolic aortic pressure augmentation. Hemodynamics, indices of LV mechanoenergetics, and coronary blood flow were measured without and after brief PULVAD support. PULVAD support decreased LV afterload and improved LV mechanical performance (increased ejection fraction, stroke volume, cardiac output and maximum elastance). The PULVAD concurrently reduced LV energy consumption (decreased stroke work and pressure-volume area) and optimized LV energetic performance (improved the ratio of stroke work to pressure-volume area). PULVAD support increased mean coronary blood flow, through dramatic augmentation of diastolic blood flow. In conclusion, the PULVAD unloads the failing LV, optimizes LV mechanoenergetics, and augments coronary blood flow. These salutary effects of short-term PULVAD support provide the foundation for long-term testing.