Strong Early Phase Parasympathetic Inhibition Followed by Sympathetic Withdrawal During Propofol Induction: Temporal Response Assessed by Wavelet-Based Spectral Analysis and Photoplethysmography.

Background: Induction of anesthesia with propofol is associated with a disturbance in hemodynamics, in part due to its effects on parasympathetic and sympathetic tone. The impact of propofol on autonomic function is unclear. In this study, we investigated in detail the changes in the cardiac autonomic nervous system (ANS) and peripheral sympathetic outflow that occur during the induction of anesthesia. Methods: Electrocardiography and pulse photoplethysmography (PPG) signals were recorded and analyzed from 30 s before to 120 s after propofol induction. The spectrogram was derived by continuous wavelet transform with the power of instantaneous high-frequency (HFi) and low-frequency (LFi) bands extracted at 1-s intervals. The wavelet-based parameters were then divided into the following segments: (1) baseline (30 s before administration of propofol), (2) early phase (first minute after administration of propofol), and (3) late phase (second minute after administration of propofol) and compared with the same time intervals of the Fourier-based spectrum [high-frequency (HF) and low-frequency (LF) bands]. Time-dependent effects were explored using fractional polynomials and repeated-measures analysis of variance. Results: Administration of propofol resulted in reductions in HFi and LFi and increases in the LFi/HFi ratio and PPG amplitude, which had a significant non-linear relationship. Significant between-group differences were found in the HFi, LFi, and LFi/HFi ratio and Fourier-based HF and LF after dividing the segments into baseline and early/late phases. On post hoc analysis, changes in HFi, LFi, and the LFi/HFi ratio were significant starting from the early phase. The corresponding effect size (partial eta squared) was > 0.3, achieving power over 90%; however, significant decreases in HF and LF were observed only in the late phase. The PPG amplitude was increased significantly in both the early and late phases. Conclusion: Propofol induction results in significant immediate changes in ANS activity that include temporally relative elevation of cardiac sympathovagal balance and reduced sympathetic activity. Clinical Trial Registration: The study was approved by the Institutional Review Board of Taipei Veterans General Hospital (No. 2017-07-009CC) and is registered at ClinicalTrials.gov (https://clinicaltrials.gov/ct2/show/NCT03613961).

A Decade of Experience Using mTor Inhibitors in Liver Transplantation.

Some studies suggest that Sirolimus (SRL) is associated with an increased risk of death in liver transplant recipients compared to treatment with calcineurin inhibitors (CNIs). We compared patients who received SRL or CNI in the first year after liver transplant. Our database included 688 patients who received a liver transplant. The patients were divided into groups. (1) CNI + MPS (mycophenolate sodium) at time of discharge. (2) CNI + MPS at time of discharge; SRL was added within the first 6 months and continued through the first year. (3) CNI + MPS at time of discharge; SRL was added within the first 6 months and discontinued before the first year. (4) SRL as primary immunosuppression. (5) SRL as primary immunosuppression and discontinued before the first year. We used mortality and graft loss as the primary measures of outcome. We also quantified renal function using the change in glomerular filtration rate (GFR), the presence of biopsy proven acute cellular reject (ACR), and steroid-resistant rejection (SRR). There were no significant differences in mortality or graft loss. There was no difference in patient or graft survival. Patients that received SRL as primary immunosuppression had 50% less rejection compared to controls.

Differential effects of plasma and red blood cell transfusions on acute lung injury and infection risk following liver transplantation.

Patients with chronic liver disease have an increased risk of developing transfusion-related acute lung injury (TRALI) from plasma-containing blood products. Similarly, red blood cell transfusions have been associated with postoperative and nosocomial infections in surgical and critical care populations. Patients undergoing liver transplantation receive large amounts of cellular and plasma-containing blood components, but it is presently unclear which blood components are associated with these postoperative complications. A retrospective cohort study of 525 consecutive liver transplant patients revealed a perioperative TRALI rate of 1.3% (7/525, 95% confidence interval = 0.6%-2.7%), which was associated with increases in the hospital mortality rate [28.6% (2/7) versus 2.9% (15/518), P = 0.02] and the intensive care unit length of stay [2 (1-11 days) versus 0 days (0-2 days), P = 0.03]. Only high-plasma-containing blood products (plasma and platelets) were associated with the development of TRALI. Seventy-four of 525 patients (14.1%) developed a postoperative infection, and this was also associated with increased in-hospital mortality [10.8% (8/74) versus 2.0% (9/451), P < 0.01] and a prolonged length of stay. Multivariate logistic regression determined that the number of transfused red blood cell units (adjusted odds ratio = 1.08, 95% confidence interval = 1.02-1.14, P < 0.01), the presence of perioperative renal dysfunction, and reoperation were significantly associated with postoperative infection. In conclusion, patients undergoing liver transplantation have a high risk of developing postoperative complications from blood transfusion. Plasma-containing blood products were associated with the development of TRALI, whereas red blood cells were associated with the development of postoperative infections in a dose-dependent manner.

Sirolimus and liver transplantation: clinical implications for hepatocellular carcinoma.

Sirolimus (SRL) is a macrolide antibiotic that has potent antifungal and immunosuppressive properties; preclinical studies suggest that SRL may possess a significant antiproliferative influence in vitro. Recently, several studies have documented a negative effect by SRL on both primary tumor growth and the proliferation of metastatic foci in various rodent models of hepatocellular carcinoma (HCC). Orthotopic liver transplantation (OLT) is increasingly becoming a viable treatment option for patients with end stage liver disease and concomitant HCC. As such, an immunosuppressive agent with antineoplastic activity is inherently attractive in the setting of OLT for malignancy. Regrettably, the cumulative experience with SRL-based immunosuppression in this patient population is limited. Herein, the authors review the experience to date with SRL as a primary immunosuppressive agent following OLT, and discuss the clinical implications of SRL-based therapy in OLT recipients with cirrhosis and cancer.

Evaluation of the splanchnic circulation with indocyanine green pharmacokinetics in liver transplant patients.

Although indocyanine green (ICG) can be used to estimate cardiac output (CO) and blood volume independently, a recirculatory multicompartmental ICG model enables description of these and additional intravascular factors. This model was used to describe the effect of end-stage liver disease (ESLD) on systemic and splanchnic hemodynamics in patients undergoing orthotopic liver transplantation. ICG disposition was determined during the dissection phase in six patients with ESLD undergoing orthotopic liver transplantation and six healthy adult living liver donors. After injecting ICG, plasma concentrations were obtained for approximately 10 to 12 minutes by noninvasive pulse dye densitometry. The recirculatory model characterizes three distinct intravascular circuits: lumped parallel fast (presumably nonsplanchnic circulation) and slow peripheral (splanchnic) circuits and a central circuit (central blood volume). Mean transit time (MTT) in the fast peripheral circuit was not different in patients with ESLD and controls. However, ESLD resulted in a significant decrease in MTT in the central (0.11 +/- 0.028 [SD] v 0.24 +/- 0.094 minutes in controls; P <.001) and slow peripheral circuit (0.67 +/- 0.41 v 1.37 +/- 0.37 minutes in controls; P <.001) because of increased flows to the central and slow peripheral circuits. These findings are consistent with the described hyperdynamic systemic and splanchnic circulations in patients with ESLD. In conclusion, the ICG model is able to derive estimates of not only blood volume and CO, but also splanchnic hemodynamics under different physiological conditions. This model can be a useful tool to evaluate the effect of pharmacological manipulation of splanchnic hemodynamics.