Strategies for liver transplantation during the SARS-CoV-2 outbreak: Preliminary experience from a single center in France.

Liver transplantation (LT) during the ongoing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic is challenging given the urgent need to reallocate resources to other areas of patient care. Available guidelines recommend reorganizing transplant care, but data on clinical experience in the context of SARS-CoV-2 pandemic are scarce. Thus, we report strategies and preliminary results in LT during the peak of the SARS-CoV-2 pandemic from a single center in France. Our strategy to reorganize the transplant program included 4 main steps: optimization of available resources, especially intensive care unit capacity; multidisciplinary risk stratification of LT candidates on the waiting list; implementation of a systematic SARS-CoV-2 screening strategy prior to transplantation; and definition of optimal recipient-donor matching. After implementation of these 4 steps, we performed 10 successful LTs during the peak of the pandemic with a short median intensive care unit stay (2.5 days), benchmark posttransplant morbidity, and no occurrence of SARS-CoV-2 infection during follow-up. From this preliminary experience we conclude that efforts in resource planning, optimal recipient selection, and organ allocation strategy are key to maintain a safe LT activity. Transplant centers should be ready to readapt their practices as the pandemic evolves.

Decreased CX3CR1 messenger RNA expression is an independent molecular biomarker of early and late mortality in critically ill patients.

BACKGROUND: Chemokine (C-X3-C motif) receptor 1 (CX3CR1) was identified as the most differentially expressed gene between survivors and non-survivors in two independent cohorts of septic shock patients and was proposed as a marker of sepsis-induced immunosuppression. Whether such a biomarker is associated with mortality in the heterogeneous group of critically ill patients is unknown. The primary objective of this study was to evaluate the association between CX3CR1 messenger RNA (mRNA) expression and mortality in intensive care unit (ICU) patients. The secondary objective was to evaluate similar endpoints in the subgroup of septic shock patients. METHODS: We performed a prospective, multicentre, non-interventional study in six ICUs of university hospitals in Lyon, France. Every consecutive adult patient with systemic inflammatory response syndrome and an expected length of stay in the ICU over 2 days was included. Whole-blood CX3CR1 mRNA expression was measured by quantitative real-time polymerase chain reaction at day 1 (D1) and D3 after inclusion. RESULTS: In ICU patients (n = 725), decreased CX3CR1 mRNA expression at D1 was associated with high D7 mortality (AUC 0.70, adjusted OR [aOR] 2.03, 95 % CI 1.19-3.46), while decreased expression at D3 was associated with increased D28 mortality (AUC 0.64, aOR 2.34, 95 % CI 1.45-3.77). In septic shock patients (n = 279), similar associations were observed between decreased D1 CX3CR1 mRNA expression and D7 mortality (AUC 0.69, aOR 2.76, 95 % CI 1.32-5.75) as well as decreased D3 expression and D28 mortality (AUC 0.72, aOR 3.98, 95 % CI 1.72-9.23). These associations were independent of lactacidaemia, Simplified Acute Physiology Score II, Sepsis-related Organ Failure Assessment score and Charlson comorbidity index. CONCLUSIONS: This study represents the largest evaluation of such an mRNA marker in a heterogeneous cohort of severely injured patients. Our results show that decreased CX3CR1 mRNA expression is associated with increased mortality in ICU patients. This suggests a link between injury-induced immunosuppression and mortality in critically ill patients. In this context, the monitoring of such a host response molecular biomarker could prove very helpful for the identification of patients at high risk of death in the ICU.

Subtotal hepatectomy in swine for studying small-for-size syndrome and portal inflow modulation: is it reliable?

BACKGROUND: Small-for-size syndrome (SFSS) is a feared complication of extended liver resection and partial liver transplantation. Swine models of extended hepatectomy have been developed for studying SFSS and its different treatment options. Although portal inflow modulation (PIM) by splenectomy or splenic artery ligation (SAL) has been proposed in humans to prevent SFSS, such procedures have not yet been evaluated in swine. OBJECTIVES: The present study was designed to evaluate modifications in splanchnic haemodynamics yielded by extended hepatectomy with and without PIM in swine. METHODS: Nineteen animals underwent 70% hepatectomy (H70, n = 7), 90% hepatectomy (H90, n = 7) or sham laparotomy (H0, n = 5). Haemodynamic measurements were performed at baseline, after hepatectomy and after PIM by SAL and splenectomy. RESULTS: Portal vein flow increased after both H70 (273 ml/min/100 g versus 123 ml/min/100 g; P = 0.016) and H90 (543 ml/min/100 g versus 124 ml/min/100 g; P = 0.031), but the hepatic venous pressure gradient (HVPG) increased only after H90 (10.0 mmHg versus 3.7 mmHg; P = 0.016). Hepatic artery flow did not significantly decrease after either H70 or H90. In all three groups, neither splenectomy nor SAL induced any changes in splanchnic haemodynamics. CONCLUSIONS: Subtotal hepatectomy of 90% in swine is a reliable model for SFSS inducing a significant increase in HVPG. However, in view of the relevant differences between swine and human splanchnic anatomy, this model is inadequate for studying the effects of PIM by SAL and splenectomy.

Comparison between respiratory variations in pulse oximetry plethysmographic waveform amplitude and arterial pulse pressure during major abdominal surgery.

BACKGROUND: To assess preload dependence, the variation of the plethysmographic waveform of pulse oximetry (ΔPOP) has been proposed as a surrogate of the pulse pressure variation (ΔPP). The aim of the study was to assess the ability of the pulse oximeter-derived plethysmographic analysis to accurately trend ΔPP in patients undergoing major abdominal surgery by using standard monitors. METHODS: A continuous recording of arterial and plethysmographic waveform was performed in 43 patients undergoing abdominal surgery. ΔPP and ΔPOP were calculated on validated respiratory cycles. RESULTS: For analysis, 92,467 respiratory cycles were kept (73.5% of cycles recorded in 40 patients). The mean of intrapatient coefficients of correlation was low (r = 0.22). The Bland and Altman analysis showed a systematic bias of 5.21; the ΔPOP being greater than the ΔPP, this bias increased with the mean value of the two indices and the limits of agreement were wide (upper 21.7% and lower -11.3%). Considering a ΔPP threshold at 12% to classify respiratory cycles as responders and nonresponders, the corresponding best cutoff value of ΔPOP was 13.6 ± 4.3%. Using these threshold values, the observed classification agreement was moderate (κ = 0.50 ± 0.09). CONCLUSIONS: The wide limits of agreement between ΔPP and ΔPOP and the weak correlation between both values cast doubt regarding the ability of ΔPOP to substitute ΔPP to follow trend in preload dependence and classify respiratory cycles as responders or nonresponders using standard monitor during anesthesia for major abdominal surgery.

The evolution of diastolic function during liver transplantation.

INTRODUCTION: The peroperative management of liver transplantation is still associated with many cardiocirculatory complications in which diastolic dysfunction may play a contributive role. Transoesophageal echocardiography is a monitoring device commonly used in liver transplantation allowing diastolic function assessment. METHODS: We prospectively analysed the peroperative transoesophageal echocardiography recordings of 40 patients undergoing liver transplantation in order to describe changes in diastolic function at different steps of the surgery. The diastolic function marker we used was the lateral mitral annulus motion (E' wave velocity) obtained by tissue-Doppler imaging. In addition, we also studied the left ventricular filling pressure indices and systolic function. RESULTS: As a whole, there was no global change in E' wave velocity throughout the surgery. However, 11 patients (27.5%) presented a decrease in E' wave velocity up to 15% that identified an occurrence of diastolic function alteration. In this group, other peroperative data were not different from other patients (amount of bleeding, fluid administration or vasopressive support). Conversely, this group experienced lower preoperative E' wave velocity values (9cm·s-1 versus 12cm·s-1, P=0.05) and an increased incidence of postoperative cardiorespiratory complications (OR=6 [1-56], P=0.02). Considering all patients, 18 patients had an E' wave velocity under 10cm·s-1 at unclamping, characterizing a diastolic dysfunction according to the usual criteria. This dysfunction was not associated with cardiorespiratory complications. CONCLUSION: This work investigated peroperative systematic echocardiographic evaluation of diastolic function during liver transplantation. Diastolic dysfunction occurs frequently during liver transplantation and could lead to postoperative cardiorespiratory complications.

Successful modulation of portal inflow by somatostatin in a porcine model of small-for-size syndrome.

BACKGROUND: Somatostatin may prevent the small-for-size syndrome in subjects undergoing extended hepatectomy by decreasing portal pressure. METHODS: Twenty pigs underwent 70% hepatectomy (H70 group, n = 7), 90% hepatectomy (H90 group, n = 7), or sham laparotomy (control group, n = 6). Splanchnic hemodynamics was measured before and after an intraoperative infusion of somatostatin. RESULTS: The portal vein flow normalized to liver weight increased in both H70 and H90 groups (from 125 ± 42 to 342 ± 82 mL/min/100g, P = .031 and from 140 ± 46 to 530 ± 241, P = .016, respectively). The hepatic venous pressure gradient (HVPG) increased in the H90 group only (from 5.5 ± 5.8 to 13 ± 4.9 mm Hg, P = .004). Somatostatin decreased portal vein flow normalized to liver weight in both H70 and H90 groups (from 408 ± 224 to 360 ± 227 mL/min/100g, P = .031 and from 560 ± 190 to 466 ± 189 mL/min/100g, P = .016), and restored a normal HVPG in the H90 group (from 14.3 ± 4.8 to 7.7 ± 6.1 mm Hg, P = .047). CONCLUSIONS: Somatostatin restores a normal HVPG in the setting of small-for-size syndrome and can be considered as an effective pharmaceutical modality of portal inflow modulation after extended hepatectomy.