Detection and quantification of perioperative heparin-like effects by rotational thromboelastometry in living-donor liver transplant recipients: A prospective observational study.

Background and Aims: Heparin-like effects (HLEs) can affect hemostasis during liver transplantation. The aim of this study was to assess the perioperative incidence and severity of HLE with rotational thromboelastometry (ROTEM) and activated partial thromboplastin time (aPTT). Material and Methods: ROTEM and aPTT were measured intraoperatively and on postoperative days (POD) 1, 3, and 7. HLE was identified if ROTEM INTEM/HEPTEM CT-ratio was >1.25 and severe forms of HLE when ratio was ≥2. Based on aPTT, HLE was defined when aPTT ratio was >1.25 (patient aPTT/control aPTT). Results: Thirty-eight recipients were included. Variable degrees of HLE were detected by aPTT-ratio and INTEM/HEPTEM CT ratio. No significant correlation existed between both ratios. Based on INTEM/HEPTEM CT ratio, HLE was detected in 7/38 during anhepatic phase, 19/38 post-reperfusion, 10/38 on POD1, 4/38 on POD3, and 0/38 on POD7. Four cases of severe HLE were identified by INTEM/HEPTEM CT ratio only in the anhepatic phase. Postoperative infusion of unfractionated heparin led to mild-moderate HLE on POD1 and 3 as evident by both tests. Red blood cell and plasma transfusion were higher with severe HLE (1350 ± 191 ml and 3558 ± 1407 ml). Composite adverse outcome of any complication or death within 3 months for patients without HLE, mild-moderate HLE, and severe HLE as detected by ROTEM was 27.8%, 42.9%, and 66.7%, respectively. Conclusion: INTEM/HEPTEM CT ratio was able to detect and quantify HLE as aPTT ratio. The ability of the INTEM/HEPTEM CT ratio to identify severe HLE earlier in the anhepatic phase needs to be studied in a larger population. HLE is self-limiting, but when identified in a severe form, it is associated with worse outcome.

Monitoring the effects of automated gas control of sevoflurane versus target-guided propofol infusion on hemodynamics of liver patients during liver resection. A randomized controlled trial.

Background and Aims: Cirrhotic patients are prone to hypotension during anesthesia. The primary aim of the study was to compare the effects of automated gas control (AGC) of sevoflurane and target-controlled infusion (TCI) of propofol on systemic and cardiac hemodynamics in hepatitis C cirrhotic patients undergoing surgery. The secondary aim was to compare the recovery, complications, and costs between the two groups. Material and Methods: This was a randomized controlled trial in adults with hepatitis C cirrhosis (Child A) who underwent open liver resection and received AGC (n = 25) or TCI (n = 25). AGC was initially set at FiO2 40% and end-tidal sevoflurane (ET SEVO) at 2.0% with a fresh gas flow of 300 mL/min. TCI of propofol was given using Marsh pharmacokinetic mode with an initial propofol target concentration (Cpt) of 4 µg/mL. Bispectral index score (BIS) was maintained between 40 and 60. Invasive arterial blood pressure (IBP), electrical cardiometry (EC), cardiac output (CO), and systemic vascular resistance (SVR), Fi SEVO, ET SEVO, propofol Cpt, and effect-site concentration (Ce) were recorded. Results: IBP and EC CO, and SVR were least affected by TCI propofol. Only one (4.00%) patient required vasopressors with TCI vs. 4 (16.00%) with AGC (χ2 (Y) (df = 1) = 0.88, P (Y) = 0.34). There was no delayed recovery, hypoxia, or awareness; however, ICU stay was shorter with TCI, (P = 0.006). BIS and EC guided median of ET SEVO was 1.90%, Fi SEVO was 2.10% with AGC, and propofol Cpt and Ce were 3.00 µg/dL with TCI. Only 0.14 [0.12-0.15] mL/min of SEVO was consumed with AGC and 0.87 [0.85-0.97] mL/min propofol with TCI. The cost was higher with TCI, P < 0.00. Conclusions: Both techniques are well tolerated hemodynamically, but TCI-propofol was found to be hemodynamically better. The recovery and complications were comparable in both groups, but TCI Propofol infusion was costlier.

The respiratory and hemodynamic effects of alveolar recruitment in cirrhotic patients undergoing liver resection surgery: A randomized controlled trial.

Background and Aims: Extensive surgical retraction combined with general anesthesia increase alveolar collapse. The primary aim of our study was to investigate the effect of alveolar recruitment maneuver (ARM) on arterial oxygenation tension (PaO2). The secondary aim was to observe its effect on hemodynamics parameters in hepatic patients during liver resection, to investigate its impact on blood loss, postoperative pulmonary complications (PPC), remnant liver function tests, and on the outcome. Material and Methods: Adult patients scheduled for liver resection were randomized into two groups: ARM (n = 21) and control (C) (n = 21). Stepwise ARM was initiated after intubation and was repeated post-retraction. Pressure-control ventilation mode was adjusted to deliver a tidal volume (Vt) of 6 mL/kg and an inspiratory-to-expiratory time (I:E) ratio of 1:2 with an optimal positive end-expiratory pressure (PEEP) for the ARM group. In the C group, a fixed PEEP (5 cmH2O) was applied. Invasive intra-arterial blood pressure (IBP), central venous pressure (CVP), electrical cardiometry (EC), alanine transaminase (ALT, U/L), and aspartate aminotransferase (AST, U/L) blood levels were monitored. Results: ARM increased PEEP, dynamic compliances, and arterial oxygenation, but reduced ventilator driving pressure compared to group C (P < 0.01). IBP, cardiac output (CO), and stroke volume variation were not affected by the higher PEEP in the ARM group (P > 0.05) but the CVP increased significantly (P = 0.001). Blood loss was not different between the ARM and C groups (1700 (1150-2000) mL vs 1110 (900-2400) mL, respectively and P = 0.57). ARM reduced postoperative oxygen desaturation; however, it did not affect the increase in remnant liver enzymes and was comparable to group C (ALT, P = 0.54, AST, P = 0.41). Conclusions: ARM improved intraoperative lung mechanics and reduced oxygen desaturation episodes in recovery, but not PPC or ICU stay. ARM was tolerated with minimal cardiac and systemic hemodynamic effects.

Monitoring haemodynamic changes during transjugular portosystemic shunt insertion with electric cardiometry in sedated and spontaneous breathing patients. A diagnostic test accuracy study.

Background and Aims: Transjugular intrahepatic portosystemic shunt (TIPS) allows a high blood volume into systemic circulation abruptly. The primary aim of the study was to investigate the effect of TIPS on systemic, portal hemodynamics, and electric cardiometry (EC) parameters in sedated and spontaneous breathing patients. Secondary aims?? Material and Methods: Adult consecutive hepatic patients scheduled for elective TIPS were included. Patients were sedated with bispectral index-guided propofol infusion + fentanyl boluses. EC parameters, i.e., cardiac output (CO) and systemic vascular resistance (SVR) were noted. Noninvasive blood pressure, heart rate, central venous pressure (CVP, cmH2O), and portal venous pressure (PVP, cmH2O) were measured pre- and post-TIPS. Results: Thirty-six people were enrolled (n = 25 included) from Aug 2018 to Dec 2019. Data (expressed in median (IQ)) were: age 33 (27-40) years, body mass index 24 (22.0-27) kg/m2, child A 60%, B 36%, and C 4%. Post-TIPS, PVP decreased (from 40 [37-45] to 34 [27-37] mmHg, P < 0.001), whereas CVP increased (from 7 [4-10] to 16 [10.0-19.0] mmHg, P < 0.001). The CO increased (P = 0.03) and SVR reduced (P = 0.012). Conclusion: The reduction in PVP following successful TIPS insertion elevated the CVP abruptly. EC was able to monitor an immediate increase in the CO and a reduction in SVR in association with the above PVP and CVP changes. The results of this unique study indicate that EC monitoring is promising; however, further evaluation in a larger population and in correlation with other gold-standard CO monitors is still indicated.

Patient-controlled analgesia with and without transverse abdominis plane and rectus sheath space block in cirrhotic patients undergoing liver resection.

BACKGROUND AND AIMS: Optimal pain control can be a challenge in cirrhotic patients. The aim was to compare the analgesic efficacy and side effects of intravenous fentanyl patient-controlled analgesia (PCA) with and without bupivacaine boluses in transversus abdominis plane (TAP) and rectus sheath space (RSB) in cirrhotics undergoing liver surgery. MATERIAL AND METHODS: A double-blinded randomized controlled trial (n = 55, child's A) was conducted. Catheters were inserted surgically in TAP and rectal sheath space during surgical closure. Fentanyl PCA + TAP + RSB group (gp) (n = 30): (0.2 ml/kg of 0.25% bupivacaine, 8 hourly) was compared with fentanyl PCA gp (n = 25): [0.2 ml/kg of saline (placebo) injected in catheters 8 hourly] for 48 h postoperatively. Plasma bupivacaine was measured with an enzyme-linked immunosorbent assay at 10 min, 30 min, 1 h, 2 h, and 4 h after each injection and 30 min before next injection. RESULTS: Fentanyl consumption was reduced in (PCA + TAP + RSB) gp compared to PCA gp (Day 1: 325.4 ± 169.1 vs. 1034 ± 231.7, Day 2: 204.44 ± 62.9 vs. 481.6 ± 158.3 µg, P < 0.05). Both groups demonstrated effective pain control at rest [Visual Analog Scales (VAS) <3), but on movement pain control with bupivacaine was better (P < 0.05). Increased demand for rescue opioids was observed prior to next scheduled bupivacaine injection in 10/30 patients on Day 1 and 2/30 on Day 2, in association with a reduced bupivacaine serum levels compared to 10 min after injection (47.6 ± 22.7 vs. 93.6 ± 61.0 ng/ml, respectively, P < 0.05). Bupivacaine did not exceed referred toxic levels. CONCLUSION: Repeated bupivacaine TAP and RSB with PCA fentanyl improved pain control, reduced opioids demand with no toxicity. Time interval between injections needs to be reduced to avoid breakthrough pain.

Perioperative Thromboelastometry for Adult Living Donor Liver Transplant Recipients with a Tendency to Hypercoagulability: A Prospective Observational Cohort Study.

BACKGROUND: Hypercoagulability can lead to serious thromboembolic events. The aim of this study was to assess the perioperative coagulation status in liver transplant recipients with a tendency to hypercoagulability. METHODS: In a prospective observational study (South African Cochrane Registry 201405000814129), 151 potential liver transplant recipients were screened for thrombophilic factors from October 2014 to June 2017, and 57 potential recipients fulfilled the inclusion criterion of presenting two or more of the following thrombophilic factors: low protein C, low protein S, low anti-thrombin, increased homocystein, increased antiphospholipid IgG/IgM antibodies, increased lupus anticoagulant, and positive Factor V Leiden mutation. Seven patients were excluded from the study because they fulfilled the exclusion criteria of cancelling the liver transplantation, oral anticoagulation, or intraoperative treatment with rFVIIa. Accordingly, 50 patients were included in the final analysis. Thromboelastometry (ROTEM) (EXTEM, INTEM and FIBTEM) and conventional coagulation tests (CCT) were performed preoperatively, during the anhepatic phase, post reperfusion, and on postoperative days (POD) 1, 3 and 7. ROTEM was used to guide blood product transfusion. Heparin was infused (60-180 U/kg/day) postoperatively for 3 days and then was replaced by low-molecular-weight heparin (20 mg/12 h). RESULTS: FIBTEM MCF significantly increased postoperatively above reference range on POD 7 despite normal fibrinogen plasma concentrations (p < 0.05). Both EXTEM and INTEM demonstrated significant changes with the phases of transplantation (p < 0.05), but with no intra- or postoperative hypercoagulability observed. INTEM CT (reference range, 100-240 s) normalized on POD 3 and 7 (196.1 ± 69.0 and 182.7 ± 63.8 s, respectively), despite prolonged aPTT (59.7 ± 18.7 and 46.4 ± 15.7 s, respectively; reference range, 20-40 s). Hepatic artery thrombosis (HAT) and portal vein thrombosis (PVT) were reported in 12.0% and 2.0%, respectively, mainly after critical care discharge and with high FIBTEM MCF values in 57% on POD 3 and 86% on POD 7. Receiver operating characteristics curve analyses of FIBTEM MCF were significant predictors for thromboembolic events with optimum cut-off, area under the curve and standard error on POD 3 (>23 mm, 0.779 and 0.097; p = 0.004) and POD 7 (>28 mm, 0.706 and 0.089; p = 0.020). Red blood cells (mean ± SD, 8.68 ± 5.81 units) were transfused in 76%, fresh frozen plasma (8.26 ± 4.14 units) in 62%, and cryoprecipitate (12.0 ± 3.68 units) in 28% of recipients. None of the recipients received intraoperative platelet transfusion or any postoperative transfusion. Main transplant indication was hepatitis C infection in 82%. 76% of recipients included in this highly selected patient population showed increased lupus anticoagulant, 2% increased antiphospholipid IgG/IgM antibodies, 20% increased homocysteine, 74% decreased anti-thrombin, 78% decreased protein C, 34% decreased protein S, and 24% a positive Factor V Leiden mutation. Overall 1-year survival was 62%. CONCLUSION: A significant postoperative step-wise increase in FIBTEM MCF beyond the reference range was observed despite normal fibrinogen plasma concentrations, and FIBTEM MCF was a predictor for thromboembolic events in this study population, particularly after POD 3 and 7 on surgical wards when CCTs failed to detect this condition. However, the predictive value of FIBTEM MCF for postoperative HAT and PVT needs to be confirmed in a larger patient population. A ROTEM-guided anticoagulation regime needs to be developed and investigated in future studies.

Impact of terlipressin infusion during and after live donor liver transplantation on incidence of acute kidney injury and neutrophil gelatinase-associated lipocalin serum levels: A randomized controlled trial.

BACKGROUND AND AIM: Acute kidney injury (AKI) with liver transplantation (LT) is not uncommon. Impact of terlipressin infusion on AKI, hemodynamics, and plasma concentration of neutrophil gelatinase-associated lipocalin (NGAL) was studied. METHODS: Patients (n=50) were randomized (NCT02059460, USA) into two equal groups: terlipressin vs Controls. Terlipressin (1-4 µg/kg/h) was administrated for 5 days. Intraoperative transesophageal Doppler for hemodynamic management. Renal functions, peak portal vein blood flow velocity (PPV), and hepatic artery resistive index (HARI) were recorded. Plasma NGAL (pNGAL) was measured baseline, 2 and 24 hours postreperfusion. RESULTS: Hepatitis C virus (HCV) was the main etiology. Age, sex, model of end-stage liver disease (MELD), and renal functions were comparable. Postoperative AKI incidence and NGAL concentrations were comparable (P>.05) between terlipressin and controls groups (44% vs 48% and 112.5±9 vs 93.1±8 ng/mL), respectively, but intraoperative NGAL in both groups increased significantly 2 hours postreperfusion (P<.05). The three NGAL readings were comparable (P>.05) between AKI (n=23) and non-AKI developers (n=27). Mean arterial blood pressure (MAP) was maintained in both groups with less systemic vascular resistance (SVR) fluctuations with terlipressin. Median norepinephrine consumption was lower in terlipressin vs controls (8 vs 12 mg; P=.04). The PPV and HARI were not affected by terlipressin at any stage (P>.05). CONCLUSION: Postliver transplant AKI was not prevented by terlipressin use nor predicted by NGAL levels.

Comparison Between 2 Strategies of Fluid Management on Blood Loss and Transfusion Requirements During Liver Transplantation.

OBJECTIVE: To compare the effects of low central venous pressure (LCVP) and transesophageal Doppler (TED)-guided fluid management on blood loss and blood transfusion during liver transplantation (LTx). DESIGN: Retrospective study. SETTING: Single institution, university hospital. PARTICIPANTS: Adult recipients of LTx. INTERVENTIONS: Two groups: control (LCVP G), n=45 with CVP maintained 40% lower than the preoperative value during the preanhepatic phase. The mean arterial pressure was kept >60 mmHg. This group was matched with the second group (TED G); n = 45, in which a TED protocol was followed maintaining the systemic vascular resistance (SVR) more than 750 dynes•s•cm-5. Coagulation defects were corrected following thromboelastometry. MEASUREMENTS AND MAIN RESULTS: Intraoperative blood loss, blood products, perioperative creatinine, lactate, and postoperative patients' stratification according to the Acute Kidney Injury Network classification were compared. Prior to the anhepatic phase, CVP was significantly lower in LCVP G (p < 0.001). TED G tended to have less but nonsignificant, blood loss, packed red blood cells, fresh frozen plasma, and platelets and received significantly less colloid and higher norepinephrine. Lactate was significantly higher in LCVP G at the end of the anhepatic phase and end of surgery while urine output in the preanhepatic phase was significantly lower. Creatinine was significantly lower on postoperative days 1 and 3, and Acute Kidney Injury Network stages were better on postoperative day 1 in TED G. CONCLUSIONS: During LTx, TED-guided fluid management, with norepinephrine used to maintain SVR, was similar to LCVP regarding blood loss and transfusion requirements and had better impacts on kidney function and lactate.

The effect of intravenous infusion of N-acetyl cysteine in cirrhotic patients undergoing liver resection: A randomized controlled trial.

BACKGROUND AND AIMS: Liver resection can lead to hepatocellular dysfunction. The aim was to evaluate the effect of N-acetyl cysteine (NAC) on liver enzymes (alanine aminotransferase [ALT] and aspartate aminotransferase [AST]), international normalized ratio (INR), C-reactive protein (CRP), and intercellular adhesion molecule 1 (ICAM 1) in cirrhotic patients undergoing liver resection. MATERIAL AND METHODS: A randomized controlled trial (RCT), Pan African Clinical Trial registry (PACTR201508001251260). 60 Child A patients were studied. NAC group (n = 30) received intravenous infusion of NAC 10 g/24 h in 250 ml of 5% dextrose during surgery and for 2 days. Controls (C) (n = 30) received a similar volume of 5% dextrose. All above parameter were measured during and after surgery. RESULTS: ALT and AST were significantly elevated after surgery, but to a less extent with NAC versus C (day 3; 118.3 ± 18.6 vs. 145.4 ± 14.0 U/L. P < 0.01) and (121.5 ± 19.5 vs. 146.6 ± 15.1 U/L, P = 0.00), respectively. Lower serum CRP and ICAM 1 with NAC versus C on day 3 (44.2 ± 13.4 vs. 68.7 ± 48.2 mg/l, P = 0.003), (308.8 ± 38.2 vs. 352.8 ± 59.4 ng/ml, P = 0.002), respectively. Hospital stay was shorter with NAC versus C (6.1 ± 0.8 vs. 6.9 ± 1.2 days, P = 0.006). Duration of surgery, INR, and hemodynamics were comparable. CONCLUSION: Prophylactic NAC in hepatic patients undergoing liver surgery attenuated postoperative increase in transaminases, ICAM 1, and CRP blood levels. The impact of these findings and the cost benefit of reduced hospital stay on enhanced recovery after surgery needs to be evaluated.

Preoperative Thromboelastometry as a Predictor of Transfusion Requirements during Adult Living Donor Liver Transplantation.

BACKGROUND: The ability to predict transfusion requirements may improve perioperative bleeding management as an integral part of a patient blood management program. Therefore, the aim of our study was to evaluate preoperative thromboelastometry as a predictor of transfusion requirements for adult living donor liver transplant recipients. METHODS: The correlation between preoperative thromboelastometry variables in 100 adult living donor liver transplant recipients and intraoperative blood transfusion requirements was examined by univariate and multivariate linear regression analysis. Thresholds of thromboelastometric parameters for prediction of packed red blood cells (PRBCs), fresh frozen plasma (FFP), platelets, and cryoprecipitate transfusion requirements were determined with receiver operating characteristics analysis. The attending anesthetists were blinded to the preoperative thromboelastometric analysis. However, a thromboelastometry-guided transfusion algorithm with predefined trigger values was used intraoperatively. The transfusion triggers in this algorithm did not change during the study period. RESULTS: Univariate analysis confirmed significant correlations between PRBCs, FFP, platelets or cryoprecipitate transfusion requirements and most thromboelastometric variables. Backward stepwise logistic regression indicated that EXTEM coagulation time (CT), maximum clot firmness (MCF) and INTEM CT, clot formation time (CFT) and MCF are independent predictors for PRBC transfusion. EXTEM CT, CFT and FIBTEM MCF are independent predictors for FFP transfusion. Only EXTEM and INTEM MCF were independent predictors of platelet transfusion. EXTEM CFT and MCF, INTEM CT, CFT and MCF as well as FIBTEM MCF are independent predictors for cryoprecipitate transfusion. Thromboelastometry-based regression equation accounted for 63% of PRBC, 83% of FFP, 61% of cryoprecipitate, and 44% of platelet transfusion requirements. CONCLUSION: Preoperative thromboelastometric analysis is helpful to predict transfusion requirements in adult living donor liver transplant recipients. This may allow for better preparation and less cross-matching prior to surgery. The findings of our study need to be re-validated in a second prospective patient population.

Comparison between intravenous patient controlled analgesia and patient controlled epidural analgesia in cirrhotic patients after hepatic resection.

BACKGROUND: Postoperative pain is one of the most important problems that confront surgical patients. The aim of this work is to compare pain control using intravenous patient controlled analgesia (PCA) and patient controlled epidural analgesia (PCEA) in cirrhotic patients undergoing elective hepatic resection. METHODS: Thirty four adult patients ASAI and II scheduled for liver resection were randomly allocated into two groups-Group (P) with I.V (PCA) with fentanyl and Group (E) (PCEA) via epidural catheter using Bubivacaine 0.125% plus 2 microgram per ml fentanyl. Coagulation changes were followed and pain score was compared in both groups. RESULTS: 34 child A cirrhotic patients, undergoing liver resection were studied. The demographic data were comparable in both groups. There was a significant decrease in pain score in both groups during the follow up period when compared to their initial score. When comparing average pain score between both groups, the PCEA group had significantly lower values. The changes in prothrombin time (PT), INR, and hemoglobin (Hb), were significant all over the follow up period compared to their corresponding base line values. 2 cases needed FFP to normalize the INR for epidural removal. There was no significant difference regarding postoperative nausea and vomiting (PONV) in both groups, no clinical manifestation suggesting epidural hematoma, and no cases were recorded to have respiratory depression. There were no significant differences in patient satisfaction and ICU stay. CONCLUSION: The two modalities of pain control seems to be nearly equivalent, but considering the risk of epidural catheter insertion and removal in cirrhotic patients who are further exposed to hepatectomy with subsequent additional coagulopathy, it may be wise to consider IVPCA technique as a policy for pain management in cirrhotic patient undergoing hepatectomy.

Bispectral Index Guidance Reduced Target Plasma Propofol Concentration During ERCP in Patients with Liver Cirrhosis.

Objective: The primary aim of this study was to investigate the guidance effect of the bispectral index (BIS) on the target plasma concentration (TPC) of propofol required for deep sedation during endoscopic retrograde cholangiopancreatography (ERCP). Second, to identify propofol consumption, recovery time, and adverse events. Methods: A total of 42 consecutive patients with liver cirrhosis and 43 consecutive patients with healthy livers were enrolled. Propofol was administered via a target control infusion (TCI) syringe pump (Marsh Model) at BIS 60-70. Patients were not intubated, were placed in the prone position, and underwent spontaneous breathing. Propofol TPCs (µg mL-1) and BIS values were recorded at T0 (baseline), T1 (5 min after induction), T2 (5 min into ERCP), T3 (15 min), T4 (30 min), and T5 (recovery). Results: TPCs and propofol consumption were lower in patients with cirrhosis than in those without cirrhosis (T4: 2.7±0.5 vs. 3.3±0.4 µg mL-1), P=0.001, and 270.4±6.9 mg vs. 390.8±13.4 mg, P=0.001), respectively. Patients with cirrhosis required more time to recover (8.5±2 vs. 6.2±0.9 min, P=0.001), despite comparable ERCP durations (31.1±11.1 vs. 34±12.5 min, P=0.28). A significant decline in TPC values among patients with cirrhosis with time (T1: 3.3±0.3, T2: 3.1±0.3, T3: 2.9±0.4, T4: 2.7±0.5 µg mL-1, P=0.001), indicating a cumulative effect. One patient with cirrhosis required bag-mask ventilation, while three patients without cirrhosis were converted to general anaesthesia. Conclusion: Combining the TCI Marsh pharmacokinetic model with BIS monitoring lowered the TPC levels required for deep sedation in patients with cirrhosis compared with healthy patients and allowed for individual variations. The prone position in deeply sedated and non-intubated spontaneous breathing patients is not without the risk of hypoxia.

Viscoelastic Hemostatic Testing as a Diagnostic Tool for Hypercoagulability in Liver Transplantation: A Narrative Review.

Liver transplantation is a complex surgical procedure in which various forms of coagulation dysfunction can occur, including perioperative hypercoagulability. The hemostasis balance in liver graft recipients with end-stage liver disease can shift to thrombosis or haemorrhage, depending on the associated risk factors and clinical conditions. Hypercoagulability can result in serious complications such as thromboembolism, which can affect the vessels of the newly transplanted liver graft. Standard coagulation tests (SCTs), such as prothrombin time and activated partial thromboplastin time (aPTT), have a poor ability to diagnose and monitor an early stage of hypercoagulability. Recent studies demonstrated that viscoelastic hemostatic elastic tests (VETs), such as rotational thromboelastometry (ROTEM) and thromboelastography (TEG), are promising alternative tools for diagnosing hypercoagulability disorders. VETs measure clotting and clot formation time, clot strength (maximum clot firmness), fibrin and platelet contribution to clot firmness, and fibrinolysis, which makes them more sensitive in identifying liver graft recipients at risk for thrombosis as compared with SCTs. However, developing evidence-based guidelines for the prophylaxis and treatment of hypercoagulability based on VET results is still needed.

Effect of Splenectomy on Coagulation and Platelet Function in Adult Liver Transplant Recipients Assessed With Rotational Thromboelastometry and Standard Coagulation Tests.

OBJECTIVES: Splenectomy during liver transplant can affect platelet function. In this study, our primary aim was to assess the perioperative platelet function by rotational thromboelastometry and the effects of splenectomy on platelet function. MATERIALS AND METHODS: We studied 40 consecutive liver transplant recipients with end-stage liver disease (50% as a result of hepatitis C). Patients with splenectomy were compared with patients without splenectomy (n = 20/group). Three platelet function parameters by rotational thromboelastometry were studied: platelet activation with arachidonic acid, platelet activation with adenosine diphosphate, and platelet activation with thrombin receptor-activating peptide 6. Patients were monitored perioperatively and until postoperative day 21. Heparin was infused for 2 days postoperatively (60-180 U/kg/day), followed by administration of subcutaneous low-molecular-weight heparin (40 mg/24 h) on postoperative days 2 and 3 and oral acetylsalicylic acid when platelet count was >50 × 103/µL. RESULTS: Liver disease contributed to low perioperative platelet count and function. Patients showed significant improvement by postoperative day 14 and day 21, particularly after splenectomy. Platelet count was significantly correlated with the 3 platelet function parameters by rotational thromboelastometry (P < .001). Acetyl salicylic acid was required earlier (postoperative day 3) for patients with splenectomy (8/20) but only affected the platelet function represented by platelet activation with arachidonic acid, whereas other platelet activation pathways were less affected. Patients received no transfusions of platelet units. CONCLUSIONS: End-stage liver disease significantly contributed to low platelet function and counts before transplant. Two weeks were required for recovery of patients posttransplant, with further enhancement by splenectomy. Some recipients showed recovery that exceeded the normal reference range, which warranted monitoring. Acetyl salicylic acid only affected 1 platelet activation receptor.

Rotational thromboelastometry and standard coagulation tests for live liver donors.

PURPOSE: To study coagulation of live liver donors with standard coagulation tests (SCT) and rotational thromboelastometry (ROTEM) and investigate their relationship. METHODS: A descriptive prospective study involving 50 right hepatotomy donors with epidural catheters. ROTEM (EXTEM, INTEM, and FIBTEM represent extrinsic and intrinsic pathways of coagulation and fibrinogen activity, respectively) was measured perioperatively and on days 1, 3, 5, 10, and 30. SCTs include prothrombin time (PT), international normalized ratio (INR) of PT, activated partial thromboplastin time (aPPT), fibrinogen, and platelets. RESULTS: PT and INR reflect hypocoagulability reaching maximum on day one (16.9 ± 2.5 s, 1.4 ± 0.2, p < 0.05 compared with baseline). ROTEM was in normal ranges till day 30 with no hypercoagulability. Fibrinogen showed no correlation with maximum clot firmness (MCF) of FIBTEM (r = 0.35, p > 0.05). CFT of EXTEM was not in significant correlation with PT and INR (r = 0.16, 0.19, p > 0.05), respectively. Significant correlation between platelets and both MCF (EXTEM; r = 0.59, p = 0.004) and MCF (INTEM; r = 0.48, p = 0.027). CONCLUSION: ROTEM disagreed with SCTs and did not show the temporary hypocoagulability suggested by SCTs. Both ROTEM and SCTs showed no signs of hypercoagulability. Future studies involving ROTEM could help develop new guidelines for coagulation monitoring.

Can Non-Invasive Spectrophotometric Hemoglobin Replace Laboratory Hemoglobin Concentrations for Preoperative Anemia Screening? A Diagnostic Test Accuracy Study.

Preoperative assessment of hemoglobin concentration in blood is important to diagnose anemia. The primary aim of this prospective diagnostic test accuracy study was to monitor non-invasive spectrophotometric hemoglobin (SpHb, g/dL) concentrations among adults prior to elective surgery and to investigate the correlation and agreement of SpHb with laboratory hemoglobin (Hb, g/dl). A secondary aim was to identify the anemia cut-off values for SpHb based on the World Health Organization (WHO) definitions for anemia. This study included 151 consecutive patients (age ≥ 18 year) presenting for preoperative evaluation prior to scheduled elective general or orthopedic surgery. Results identified the mean ± SD of SpHb at 11.43 ± 2.01 g/dL, which underestimated the mean laboratory Hb (12.64 ± 2.29 g/dL, p < 0.001). A bias mean difference (SpHb-Hb) of -1.21 g/dL, with a SD of 1.76, was reported. This bias (SpHb-Hb) was inversely correlated with the mean Hb concentrations. A positive correlation existed between SpHb and Hb, with a good degree of reliability and a significant Intra Class Correlation (ICC). SpHb diagnosed anemia in 32.3% and 60.3% of males and females, respectively. The SpHb cut-off values to identify anemia were 11.3 and 10.2 g/dL for males and females, respectively, with a sensitivity of 83.3% for males and only 62.9% for females. The specificity for males and females were 81% and 91.3%, respectively. SpHb sensitivity allows for anemia diagnosis among males, but not females. However, the specificity allows SpHb to rule out anemia for both.

Inhaled Sedation with Volatile Anesthetics for Mechanically Ventilated Patients in Intensive Care Units: A Narrative Review.

Inhaled sedation was recently approved in Europe as an alternative to intravenous sedative drugs for intensive care unit (ICU) sedation. The aim of this narrative review was to summarize the available data from the literature published between 2005 and 2023 in terms of the efficacy, safety, and potential clinical benefits of inhaled sedation for ICU mechanically ventilated patients. The results indicated that inhaled sedation reduces the time to extubation and weaning from mechanical ventilation and reduces opioid and muscle relaxant consumption, thereby possibly enhancing recovery. Several researchers have reported its potential cardio-protective, anti-inflammatory or bronchodilator properties, alongside its minimal metabolism by the liver and kidney. The reflection devices used with inhaled sedation may increase the instrumental dead space volume and could lead to hypercapnia if the ventilator settings are not optimal and the end tidal carbon dioxide is not monitored. The risk of air pollution can be prevented by the adequate scavenging of the expired gases. Minimizing atmospheric pollution can be achieved through the judicious use of the inhalation sedation for selected groups of ICU patients, where the benefits are maximized compared to intravenous sedation. Very rarely, inhaled sedation can induce malignant hyperthermia, which prompts urgent diagnosis and treatment by the ICU staff. Overall, there is growing evidence to support the benefits of inhaled sedation as an alternative for intravenous sedation in ICU mechanically ventilated patients. The indication and management of any side effects should be clearly set and protocolized by each ICU. More randomized controlled trials (RCTs) are still required to investigate whether inhaled sedation should be prioritized over the current practice of intravenous sedation.

Comparing Non-Invasive Spectrophotometry to Hematology Analysis for Hemoglobin Measurements in Sickle Cell Disease Patients.

Patients with sickle cell disease (SCD) require repeated blood sampling for hemoglobin (Hb) concentration measurements. The primary aim of this study was to compare non-invasive spectrophotometric hemoglobin (SpHb, g/dL) measurements to those taken via an automated hematology analyzer (Hb, g/dL) in patients with SCD visiting outpatient clinics and to investigate the correlations and agreements between both measurement techniques. Secondarily, we aimed to identify the SpHb cut-off concentration for the diagnosis of anemia and to monitor the effects of the pleth variability index (PVI, %) and perfusion index (PI) on SpHb measurements. The results gained from the examination of one hundred and fifty-eight patients indicated that the SpHb measurements overestimated the lab Hb concentrations, with a mean (SpHb-Hb) bias of 0.82 g/dL (SD 1.29). The SpHb measurements were positively correlated with the Hb measurements (Kendall's tau correlation (τ), n = 158, τ = 0.68, p < 0.001), with an intra-class correlation (ICC) of 0.67 and a 95% CI from 0.57 to 0.74 (p = 0.000). The SpHb cut-off concentration to diagnose anemia was 11.4 and 11.7 g/dL for males and females, respectively. SpHb sensitivity was low for males and females at 64.4% and 57.1%; however, the specificity was higher at 90.9% and 75%, with positive predictive values (PPVs) of 95.6 and 85.7, respectively. No correlation existed between SpHb measurements and the PVI (%) in contrast with a moderate correlation with the PI (r = 0.049, p = 0.54, and r = 0.36, p < 0.001, respectively). The mean PI was low at 2.52 ± 1.7. In conclusion, the SpHb measurements were consistently higher than the lab Hb concentrations, with a positive correlation. The sensitivity and precision of the SpHb measurements were lower than expected. However, the SpHb specificity and its positive predictive values (PPVs) indicated that it is less likely for a patient with a positive SpHb test result for anemia to be non-anemic. These results will allow SpHb measurement to play a role in excluding the presence of anemia. In light of the low PI values determined, the SpHb measurements were challenging to take and, thus, require further technological improvements.

Respiratory and Hemodynamic Effects of Prophylactic Alveolar Recruitment During Liver Transplant: A Randomized Controlled Trial.

OBJECTIVES: Prolonged surgical retraction may cause atelectasis. We aimed to recruit collapsed alveoli, stepwise, monitored by lung dynamic compliance and observe effects on arterial oxygenation and systemic and graft hemodynamics. Secondarily, we observed alveolar recruitment effects on postoperative mechanical ventilation, international normalized ratio, and pulmonary complications. MATERIALS AND METHODS: For 58 recipients (1 excluded), randomized with optimal positive end-expiratory pressure (n = 28) versus control (fixed positive end-expiratory pressure, 5 cm H2O; n = 29), alveolar recruitment was initiated (pressure-controlled ventilation guided by lung dynamic compliance) to identify optimal conditions. Ventilation shifted to volume-control mode with 0.4 fraction of inspired oxygen, 6 mL/kg tidal volume, and 1:2 inspiratory-to-expiratory ratio. Alveolar recruitment was repeated postretraction and at intensive care unit admission. Primary endpoints were changes in lung dynamic compliance, arterial oxygenation, and hemodynamics (cardiac output, invasive arterial and central venous pressures, graft portal and hepatic vein flows). Secondary endpoints were mechanical ventilation period and postoperative international normalized ratio, aspartate/alanine aminotransferases, lactate, and pulmonary complications. RESULTS: Alveolar recruitment increased positive end-expiratory pressure, lung dynamic compliance, and arterial oxygenation (P < .01) and central venous pressure (P = .004), without effects on corrected flow time (P = .7). Cardiac output and invasive arterial pressure were stable with (P = .11) and without alveolar recruitment (P = .1), as were portal (P = .27) and hepatic vein flow (P = .30). Alveolar recruitment reduced postoperative pulmonary complications (n = 0/28 vs 8/29; P = .001), without reduction in postoperative mechanical ventilation period (P = .08). International normalization ratio, aspartate/alanine aminotransferases, and lactate were not different from control (P > .05). CONCLUSIONS: Stepwise alveolar recruitment identified the optimal positive end-expiratory pressure to improve lung mechanics and oxygenation with minimal hemodynamic changes, without liver graft congestion/dysfunction, and was associated with significant reduction in postoperative pulmonary complications.

Plethysmography Variability Index and Stroke Volume Variation Changes in Relation to Central Venous Pressure Changes During Living Related Donor Right Hepatotomy: A Diagnostic Test Accuracy.

OBJECTIVES: During donor hepatectomy, we investigated (1) the Electrical Cardiometry associations and agreements between noninvasive plethysmography variability index and noninvasive stroke volume variation, (2) their association with central venous pressure, and (3) their ability to monitor intraoperative changes and discriminate donors with increased blood loss. MATERIALS AND METHODS: A diagnostic test accuracy was applied among donors (American Society of Anesthesiologists classification I). Data were recorded at 10 minutes after anesthesia induction, hourly during dissection, after resection, and at end of surgery. Crystalloids were restricted during resection to reduce central venous pressure but were otherwise infused to maintain mean invasive arterial blood pressure >60 mm Hg and urine output >0.5 mL/kg/h. RESULTS: All 34 donors were related. Sons or daughters represented 58.8% (median age 26.0 years [interquartile range, 21.0-34.0]). Median values (with interquartile ranges) were anesthesia time, 7.5 hours (7.0-8.0); blood loss, 400 mL (400.0-500.0); infused acetated Ringer solution, 4000.0 mL (3500.0-4500.0); colloids, 250.0 mL (0-500.0); and urine output, 1.4 mL/kg/h (1.30-1.7). No blood products were transfused. Central venous pressure showed negligible negative correlations for both plethysmography variability index and stroke volume variation. Plethysmography variability index showed negligible correlation and poor agreement with stroke volume variation (P < .001, with intraclass correlation = 0.213 and a relatively wide bias; 95% CI, 0.03-0.37). All 3 methods reflected a state of normovolemia despite fluid restriction during resection and were unable to discriminate donors with increased blood loss (>400 mL). CONCLUSIONS: Plethysmography variability index and stroke volume variation showed negligible correlation and poor agreement with central venous pressure. Transfusion-free dissection was possible despite normovolemia, with median values of 8 mm Hg central venous pressure, 10% stroke volume variation, and 12% plethysmography variability index. Plethysmography variability index and stroke volume variation were unable to discriminate donors with increased blood loss.