Extracorporeal Albumin Dialysis in Liver Failure with MARS and SPAD: A Randomized Crossover Trial.

INTRODUCTION: Liver failure is associated with hepatic and extrahepatic organ failure leading to a high short-term mortality rate. Extracorporeal albumin dialysis (ECAD) aims to reduce albumin-bound toxins accumulated during liver failure. ECAD detoxifies blood using albumin dialysis through an artificial semipermeable membrane with recirculation (molecular adsorbent recirculating system, MARS) or without (single-pass albumin dialysis, SPAD). METHODS: We performed a randomized crossover open trial in a surgical intensive care unit. The primary outcome of the study was total bilirubin reduction during MARS and during SPAD therapies. The secondary outcomes were conjugated bilirubin and bile acid level reduction during MARS and SPAD sessions and tolerance of dialysis system devices. Inclusion criteria were adult patients presenting liver failure with factor V activity <50% associated with bilirubin ≥250 µmol/L and a complication (either hepatic encephalopathy, severe pruritus, or hepatorenal syndrome). For MARS and SPAD, the dialysis flow rate was equal to 1,000 mL/h. RESULTS: Twenty crossovers have been performed. Baseline biochemical characteristics (bilirubin, ammonia, bile acids, creatinine, and urea) were not statistically different between MARS and SPAD. Both ECAD have led to a significant reduction in total bilirubin (-83 ± 67 µmol/L after MARS; -122 ± 118 µmol/L after SPAD session), conjugated bilirubin (-82 ± 61 µmol/L after MARS; -105 ± 96 µmol/L after SPAD session), and bile acid levels (-64 ± 75 µmol/L after MARS; -56 ± 56 µmol/L after SPAD session), all nondifferent comparing MARS to SPAD. CONCLUSION: A simple-to-perform SPAD therapy with equal to MARS dialysate flow parameters provides the same efficacy in bilirubin and bile acid removal. However, clinically relevant endpoints have to be evaluated in randomized trials to compare MARS and SPAD therapies and to define the place of SPAD in the liver failure care program.

Prediction of intraoperative hypotension from the linear extrapolation of mean arterial pressure.

BACKGROUND: Hypotension prediction index (HPI) software is a proprietary machine learning-based algorithm used to predict intraoperative hypotension (IOH). HPI has shown superiority in predicting IOH when compared to the predictive value of changes in mean arterial pressure (ΔMAP) alone. However, the predictive value of ΔMAP alone, with no reference to the absolute level of MAP, is counterintuitive and poor at predicting IOH. A simple linear extrapolation of mean arterial pressure (LepMAP) is closer to the clinical approach. OBJECTIVES: Our primary objective was to investigate whether LepMAP better predicts IOH than ΔMAP alone. DESIGN: Retrospective diagnostic accuracy study. SETTING: Two tertiary University Hospitals between May 2019 and December 2019. PATIENTS: A total of 83 adult patients undergoing high risk non-cardiac surgery. DATA SOURCES: Arterial pressure data were automatically extracted from the anaesthesia data collection software (one value per minute). IOH was defined as MAP < 65 mmHg. ANALYSIS: Correlations for repeated measurements and the area under the curve (AUC) from receiver operating characteristics (ROC) were determined for the ability of LepMAP and ΔMAP to predict IOH at 1, 2 and 5 min before its occurrence (A-analysis, using the whole dataset). Data were also analysed after exclusion of MAP values between 65 and 75 mmHg (B-analysis). RESULTS: A total of 24 318 segments of ten minutes duration were analysed. In the A-analysis, ROC AUCs to predict IOH at 1, 2 and 5 min before its occurrence by LepMAP were 0.87 (95% confidence interval, CI, 0.86 to 0.88), 0.81 (95% CI, 0.79 to 0.83) and 0.69 (95% CI, 0.66 to 0.71) and for ΔMAP alone 0.59 (95% CI, 0.57 to 0.62), 0.61 (95% CI, 0.59 to 0.64), 0.57 (95% CI, 0.54 to 0.69), respectively. In the B analysis for LepMAP these were 0.97 (95% CI, 0.9 to 0.98), 0.93 (95% CI, 0.92 to 0.95) and 0.86 (95% CI, 0.84 to 0.88), respectively, and for ΔMAP alone 0.59 (95% CI, 0.53 to 0.58), 0.56 (95% CI, 0.54 to 0.59), 0.54 (95% CI, 0.51 to 0.57), respectively. LepMAP ROC AUCs were significantly higher than ΔMAP ROC AUCs in all cases. CONCLUSIONS: LepMAP provides reliable real-time and continuous prediction of IOH 1 and 2 min before its occurrence. LepMAP offers better discrimination than ΔMAP at 1, 2 and 5 min before its occurrence. Future studies evaluating machine learning algorithms to predict IOH should be compared with LepMAP rather than ΔMAP.

Impact of 2016 Enhanced Recovery After Surgery (ERAS) Recommendations on Outcomes after Hepatectomy in Cirrhotic and Non-Cirrhotic Patients.

BACKGROUND: The Enhanced Recovery After Surgery (ERAS) society published new recommendations for hepatectomy in 2016. Few studies have assessed their clinical impact. The aim of this monocentric study was to assess the impact of those guidelines on outcomes after liver surgery with a special focus on cirrhotic patients. METHOD: Postoperative outcomes of patients undergoing hepatectomy 30 months before and after ERAS implementation according to the 2016 ERAS guidelines were compared after inverse probability of treatment weighting (IPTW). Primary endpoint was 90-day morbidity. RESULTS: From 2015 to 2020, 430 patients underwent hepatectomy including 226 procedures performed before and 204 after ERAS implementation. After IPTW, overall morbidity (42.5% vs. 64.7%, p < 0.001), Comprehensive Complication Index (CCI) score (14.3 vs. 20.8, p = 0.004), length of stay (10.4 vs. 13.7 days, p = 0.001) and textbook outcome (50% vs. 40.2%, p = 0.022) were significantly improved in the ERAS group, while mortality and severe complications were similar in both groups. In the non-cirrhosis subgroup (n = 321), these results were confirmed. However, in the cirrhosis subgroup (n = 105), no difference appeared on outcomes after hepatectomy with an overall morbidity (47.5% vs. 65.2%, p = 0.069) and a length of stay (8 vs. 9 days, p = 0.310) which were not significantly different. The compliance rate to ERAS guidelines was 60% in both cirrhotic and non-cirrhotic subgroups. CONCLUSION: Perioperative ERAS program for hepatectomy results in improved outcomes with decreased rate of non-severe morbidity. Although those guidelines are not deleterious for cirrhotic patients, they probably require revisions to be more effective in this patient population.

The use of a thromboelastometry-based algorithm reduces the need for blood product transfusion during orthotopic liver transplantation: A randomised controlled study.

BACKGROUND: Orthotopic liver transplantation is associated with a risk of bleeding. Coagulation in cirrhotic patients is difficult to assess with standard coagulation tests because of rebalanced coagulation. This can be better assessed by thromboelastometry which can detect coagulation impairments more specifically in such patients. OBJECTIVES: Our first objective was to compare the number of units of blood products transfused during liver transplantation when using an algorithm based on standard coagulation tests or a thromboelastometry-guided transfusion algorithm. DESIGN: Randomised controlled trial. SETTING: Single-centre tertiary care hospital in France, from December 2014 to August 2016. PARTICIPANTS: A total of 81 adult patients undergoing orthotopic liver transplantation were studied. Patients were excluded if they had congenital coagulopathies. INTERVENTION: Transfusion management during liver transplantation was guided either by a standard coagulation test algorithm or by a thromboelastometry-guided algorithm. Transfusion, treatments and postoperative outcomes were compared between groups. MAIN OUTCOME MEASURES: Total number of transfused blood product units during the operative period (1 U is one pack of red blood cells (RBCs), fresh frozen plasma (FFP) or platelets). RESULTS: Median [interquartile range] intra-operative transfusion requirement was reduced in the thromboelastometry group (3 [2 to 4] vs. 7 [4 to 10] U, P = 0.005). FFP and tranexamic acid were administered less frequently in the thromboelastometry group (respectively 15 vs. 46.3%, P = 0.002 and 27.5 vs. 58.5%, P = 0.005), whereas fibrinogen was more often infused in the thromboelastometry group (72.5 vs. 29.3%, P < 0.001). Median transfusions of FFP (3 [2 to 6] vs. 4 [2 to 7] U, P = 0.448), RBCs (3 [2 to 5] vs. 4 [2 to 6] U, P = 0.330) and platelets (1 [1 to 2] vs. 1 [1 to 2] U, P = 0.910) were not different between groups. In the postoperative period, RBC or platelet transfusion, the need for revision surgery or occurrence of haemorrhage were not different between groups. CONCLUSION: A transfusion algorithm based on thromboelastometry assessment of coagulation reduced the total number of blood product units transfused during liver transplantation, particularly FFP administration. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02352181.

Incidence and Risk Factors of Coagulation Profile Derangement After Liver Surgery: Implications for the Use of Epidural Analgesia-A Retrospective Cohort Study.

BACKGROUND: Hepatic surgery is a major abdominal surgery. Epidural analgesia may decrease the incidence of postoperative morbidities. Hemostatic disorders frequently occur after hepatic resection. Insertion or withdrawal (whether accidental or not) of an epidural catheter during coagulopathic state may cause an epidural hematoma. The aim of the study is to determine the incidence of coagulopathy after hepatectomy, interfering with epidural catheter removal, and to identify the risk factors related to coagulopathy. METHODS: We performed a retrospective review of a prospective, multicenter, observational database including patients over 18 years old with a history of liver resection. Main collected data were the following: age, preexisting cirrhosis, Child-Pugh class, preoperative and postoperative coagulation profiles, extent of liver resection, blood loss, blood products transfused during surgery. International normalized ratio (INR) ≥1.5 and/or platelet count <80,000/mm defined coagulopathy according to the neuraxial anesthesia guidelines. A logistic regression analysis was performed to assess the association between selected factors and a coagulopathic state after hepatic resection. RESULTS: One thousand three hundred seventy-one patients were assessed. Seven hundred fifty-nine patients had data available about postoperative coagulopathy, which was observed in 53.5% [95% confidence interval, 50.0-57.1]. Maximum derangement in INR occurred on the first postoperative day, and platelet count reached a trough peak on postoperative days 2 and 3. In the multivariable analysis, preexisting hepatic cirrhosis (odds ratio [OR] = 2.49 [1.38-4.51]; P = .003), preoperative INR ≥1.3 (OR = 2.39 [1.10-5.17]; P = .027), preoperative platelet count <150 G/L (OR = 3.03 [1.77-5.20]; P = .004), major hepatectomy (OR = 2.96 [2.07-4.23]; P < .001), and estimated intraoperative blood loss ≥1000 mL (OR = 1.85 [1.08-3.18]; P = .025) were associated with postoperative coagulopathy. CONCLUSIONS: Coagulopathy is frequent (53.5% [95% confidence interval, 50.0-57.1]) after liver resection. Epidural analgesia seems safe in patients undergoing minor hepatic resection without preexisting hepatic cirrhosis, showing a normal preoperative INR and platelet count.

Candida albicans and non-Candida albicans fungemia in an institutional hospital during a decade.

Since the outcomes of patients with candidemia is poor and Candida spp. with increased resistance to antifungal therapy may be associated with these results, the emergence of these blood infections caused by non-C. albicans Candida spp. was explored prospectively over a two-year period (2009-2010). Candidemia was defined as the recovery of Candida spp. in culture from a patient's blood sample. The in vitro susceptibility of each isolate to amphotericin B, caspofungin, fluconazole and voriconazole was determined. In addition, characteristics of patients and outcomes were investigated in real-time. The Candida distribution was compared to that observed in a similar study 10 years earlier in the same hospital. A total of 182 patients with candidemia were included in the study. While C. albicans was the most frequently isolated species (n = 102), non-C. albicans Candida spp. included; C. glabrata (n = 32), C. parapsilosis (n = 21), C. tropicalis (n = 13), C. krusei (n = 8), C. kefyr (n = 3), C. lusitaniae (n = 2), C. lipolytica (n = 2), C. famata (n = 1), C. guilliermondii (n = 1), C. inconspicua (n = 1), C. dubliniensis (n = 1), C. sake (n = 1) and C. nivariensis (n = 1). In seven patients, C. albicans was associated with another Candida spp. Surprisingly, this prospective study demonstrated that regardless of the department (intensive care unit or hematological department), Candida spp. distribution was no different from that found in the 1998-2001 survey, except for C. krusei. A reduction in the proportion of C. krusei isolates was observed from 2000-2010 (P = 0.028) as a result of its decreased recovery in the hematological department.

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.

PCO2 gap, its ratio to arteriovenous oxygen content, ScvO2 and lactate in high-risk abdominal surgery patients: An observational study.

BACKGROUND: The difference between arterial and central venous carbon dioxide partial pressure (PCO2 gap), a marker of oxygen delivery (DO2) and oxygen consumption (VO2) adequacy, has been evaluated as a promising prognostic tool in intensive care unit (ICU) patients. We therefore sought to study the association between intraoperative PCO2 gap and postoperative complications (POC) in the perioperative setting of elective major abdominal surgery. METHODS: We conducted a single-centre prospective observational study. All adult patients who underwent major planned abdominal surgery were eligible. PCO2 gap was measured every 2 h during surgery, at ICU admission and repeated 12 h and 24 h later. Severe POC within 28 days after surgery were defined as complications graded 3 or more according to Clavien-Dindo classification. Following a univariate analysis, a multivariable analysis using a logistic regression model was performed. RESULTS: Ninety patients were included and divided into two groups according to the occurrence of POC. No significant difference was found between groups regarding baseline characteristics at inclusion. Thirty-nine (43%) patients developed postoperative complications. The median [IQR] intraoperative PCO2 gap was significantly higher in patients who had complications (6.5 [5.5-7.3] mmHg) compared to those who did not (5.0 [3.9-5.8] mmHg; p < 0.001). The area under the receiver operating characteristic curve for occurrence of POC was 0.78 for the PCO2 gap. After multivariable analysis, PCO2 gap was found independently associated with POC (OR: 14.9, 95% CI [4.68-60.1], p < 0.001) with a threshold value of 6.2 mmHg. The duration of surgery (OR: 1.01, 95% CI [1.00; 1.01], p = 0.04) and the need for vasoactive support during surgery (OR: 5.76, 95% CI [1.72; 24.1], p = 0.006) were also independently associated with POC. CONCLUSION: Intraoperative PCO2 gap is a relevant predictive factor of severe postoperative complications in high-risk elective surgery patients. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03914976.

Can Thoracic Ultrasound on Admission Predict the Outcome of Critically Ill Patients with SARS-CoV-2? A French Multi-Centric Ancillary Retrospective Study.

INTRODUCTION: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreaks have led to massive admissions to intensive care units (ICUs). An ultrasound examination of the thorax is widely performed on admission in these patients. The primary objective of our study was to assess the performance of the lung ultrasound score (LUS) on ICU admission to predict the 28-day mortality rate in patients with SARS-CoV-2. The secondary objective was to asses the performance of thoracic ultrasound and biological markers of cardiac injury to predict mortality. METHODS: This multicentre, retrospective, observational study was conducted in six ICUs of four university hospitals in France from 15 March to 3 May 2020. Patients admitted to ICUs because of SARS-CoV-2-related acute respiratory failure and those who received an LUS examination at admission were included. The area under the receiver-operating characteristics (ROC) curve was determined for the LUS score to predict the 28-day mortality rate. The same analysis was performed for the Simplified Acute Physiology Score, left ventricular ejection fraction, cardiac output, brain natriuretic peptide and ultra-sensitive troponin levels at admission. RESULTS: In 57 patients, the 28-day mortality rate was 21%. The area under the ROC curve of the LUS score value on ICU admission was 0.68 [95% CI 0.54-0.82; p = 0.05]. In non-intubated patients on ICU admission (n = 40), the area under the ROC curves was 0.84 [95% CI 0.70-0.97; p = 0.005]. The best cut-off of 22 corresponded to 85% specificity and 83% sensitivity. CONCLUSIONS: LUS scores on ICU admission for SARS-CoV-2 did not efficiently predict the 28-day mortality rate. Performance was better for non-intubated patients at admission. Performance of biological cardiac markers may be equivalent to the LUS score.

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.

Tacrolimus trough levels before, during and after jejunostomy in a liver transplant patient: a case report.

Although the feasibility of oral tacrolimus administration in the presence of jejunostomy has already been reported, few studies monitoring tacrolimus trough blood levels have been analyzed in detail, either during or after a jejunostomy closure. We report on our experience with a 34-year-old patient who underwent liver transplantations, with a proximal jejunostomy constructed a few days prior to the second transplantation. He was administered tacrolimus by a predominantly oral route, and less frequently received it by jejunostomy. The aim of this paper is to discuss this administration strategy and whether a different method could have been more suitable. This case report highlights that during the jejunostomy period, the tacrolimus doses that were required to maintain trough concentrations within the therapeutic range were four times higher than those administered after the closure of the jejunostomy. We observed an increase in the Dose-Normalized Trough Concentration (DNTC) values when tacrolimus was administered for 4 consecutive days by jejunostomy as compared to oral administration, indicating that the relative bioavailability of tacrolimus increased. Moreover, when returning to oral administration, the subsequent DNTC value was halved, highlighting a reduction in the tacrolimus bioavailability. Thus, in such a case, administration by jejunostomy could be more appropriate.