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BackgroundImmune paralysis can be defined as a hypoinflammatory state associated with the incapacity of the immune system to release proinflammatory mediators despite the clearance of pathogens by antimicrobials. Persistent immune paralysis leads to failure to eradicate primary infections with a substantial increase in the risk of multiorgan dysfunction and mortality. The state of immune paralysis is caused mainly by the diminished ability of monocytes to release proinflammatory cytokines in response to endotoxin. This phenomenon is known as endotoxin tolerance. This study aimed to assess the role of dexmedetomidine in modifying immune paralysis in septic shock patients.MethodsTwenty-four patients with septic shock were randomized into two groups of 12 patients. A continuous intravenous infusion of dexmedetomidine started at 0.15 µg kg−1 hr−1 and adjusted by 0.15 µg kg−1 h−1 to a maximum of 0.75 µg kg−1 h−1 (10 ml h−1), while midazolam was started at 1 mg h−1 (2 mL hr−1) and adjusted by 1 mg h−1 to a maximum of 5 mg h−1 (10 mL h−1). All infusions were adjusted by increments of 2 mL/hr−1 to maintain blinding. Serum levels of CD42a+/CD14+, HLADR+/CD14+, CRP, IL-6, IL-10 and TNF-α were measured at baseline (T1), 12 h (T2), and 24 h (T3).ResultsTreatment with dexmedetomidine yielded no significant difference in CD42a+/CD14+, HLADR+/CD14, CD24b-MFI, HLADR-MFI, IL6 and TREM1 at all time points when compared with midazolam treatment. There was no significant difference in TLR levels between the two groups. Cardiac output in the dexmedetomidine group showed a significant decrease at 6, 12 and 24 h (P = 0.033, 0.021, and 0.005, respectively) compared with that in the midazolam group.ConclusionOur results indicated that dexmedetomidine did not affect CD42a+/CD14+ and HLA-DR+/CD14+ expression in septic patients. Furthermore, cytokine production and inflammatory biomarkers did not change with dexmedetomidine infusion.Trial registration Clinical trial.gov registry (NCT03989609) on June 14, 2019, https://register.clinicaltrials.gov.

Background Increased lung water and the resultant atelectasis are significant pulmonary complications after cardiopulmonary bypass (CPB) in children undergoing cardiac surgery; these complications are observed after CPB than after anaesthesia alone. Ultrafiltration has been shown to decrease total body water and postoperative blood loss and improve the alveolar to arterial oxygen gradient and pulmonary compliance. This study investigated whether conventional ultrafiltration during CPB in paediatric heart surgeries influences post-bypass extravascular lung water (EVLW) assessed by lung ultrasound (LUS). Methods This randomized controlled study included 60 patients with congenital heart disease (ASA II-III), aged 1 to 48 months, with a body weight > 3 kg. Conventional ultrafiltration targeting a haematocrit (HCT) level of 28% was performed on the ultrafiltration group, while the control group did not receive ultrafiltration. LUS scores were recorded at baseline and at the end of surgery. The PaO2/FiO2 ratio (arterial oxygen tension divided by the fraction of inspired oxygen), urine output, and haemodynamic parameters were also recorded. Results LUS scores were comparable between the two groups both at baseline ( p  = 0.92) and at the end of surgery ( p  = 0.95); however, within the same group, the scores at the end of surgery significantly differed from their baseline values in both the ultrafiltration ( p  = 0.01) and non-ultrafiltration groups ( p  = 0.02). The baseline PaO2/FiO2 ratio was comparable between both groups. at the end of surgery, The PaO2/FiO2 ratio increased in the ultrafiltration group compared to that in the non-ultrafiltration group, albeit insignificant ( p  = 0.16). no correlation between the PaO2/FiO2 ratio and LUS score was found at baseline (r = − 0.21, p  = 0.31). On the other hand, post-surgical measurements were negatively correlated (r = − 0.41, p  = 0.045). Conclusion Conventional ultrafiltration did not alter the EVLW when assessed by LUS and oxygenation state. Similarly, ultrafiltration did not affect the urea and creatinine levels, intensive care unit (ICU) stays, ventilation days, or mortality. Trial registration Clinicaltrials.gov Identifier: NCT03146143 registered on 29-April-2017.

Background Surgery for aortic coarctation requires special care during anesthesia due to severe pain during the lateral thoracotomy incision, intraoperative hemodynamic instability and the need for large doses of intra- and postoperative analgesics and vasodilators. Additionally, the postoperative care of patients is very important. Aims We aimed to compare ultrasound-guided paravertebral block performed using bupivacaine alone and bupivacaine with dexamethasone in terms of the intra- and postoperative analgesic requirements and hemodynamics, postoperative complications and ICU stay. Study design This was a prospective, randomized, controlled, double-blinded study. Methods Fifty patients aged four to 12 months scheduled for aortic coarctation surgery were randomly divided into two equal groups ( n  = 25). Patients in group D (dexamethasone) received 0.5 mg/kg bupivacaine 0.25% mixed with 0.1 mg/kg dexamethasone diluted with isotonic saline and those in group C (control) received 0.5 mg/kg bupivacaine 0.25% diluted with isotonic saline (total volume 15 ml in each group). Intraoperative fentanyl consumption and hemodynamics (heart rate, arterial blood pressure) at baseline, 1 min after induction, at skin incision, after 30 min, after clamping, after declamping and at the end of the surgery were recorded, along with the objective pain score (OPS) immediately postoperatively and at 4 h, 8 h, 12 h and 24 h postoperatively and the time to the first request for pethidine. The intra- and postoperative vasodilator doses, time to extubation, ICU stay duration and postoperative complications were also recorded. Results The postoperative OPS was significantly lower at 12 and 24 h in group D than in group C. The time to the first request for analgesia was significantly longer in group D than in group C (3.9 ± 2.23 vs 8.6 ± 0.69). Additionally, the time to extubation was significantly shorter in group D. Conclusion The use of dexamethasone as an adjuvant in ultrasound-guided paravertebral block in paediatric patients undergoing surgery for aortic coarctation increased the duration of postoperative analgesia with a prolonged time to the first request for analgesics It was also associated with a decreased incidence of postoperative complications. Trial registration Trial registration number: NCT03074773 . (Prospectively registered). The initial registration date was 9/3/2017.

Major hemodynamic changes are frequently noted during liver transplantation (LT). We evaluated the performance of electrical velocimetry (EV) as compared to that of TEE in SV optimization during liver transplantation. This was an observational study in 32 patients undergoing LT. We compared SV values measured simultaneously by EV (SVEV) and TEE (SVTEE) at baseline 30 min after induction, at the end of dissection phase, 30 min after anhepatic phase, 30 min after reperfusion. We also evaluated the reliability of EV to track changes In SV before and after 49 fluid challenges. Finally, the SV variation (SVV) and pulse pressure variation (PPV) were tested as predictors for volume responsiveness, defined as an increase in SV ≥ 10% after 250 ml of colloid. For 112 paired SV data, the overall correlation was 0.76 and bias (limits of agreement) 0.3 (− 29 to 29) ml percentage error 62%. The EV was able to track changes in SV with a concordance rate of 97%, and a sensitivity and specificity of 93% to detect a positive fluid challenge. The AUC values (with 95% confidence intervals) for SVV and PPV were 0.68 (0.52–0.83) and 0.72 (0.57–0.86), respectively, indicating low predictive capacity in these setting. The absolute values of SV derived from EV did not agree with SV derived from TEE. However, EV was able to track the direction of changes in SV during hemodynamic management of patients undergoing liver transplantation.Clinical trial registration: Clinicaltrials.gov Identifier: NCT03228329 prospectively Registered on 13-July-2017.

Background Mini-fluid challenge is a well tested and effective tool to predict fluid responsiveness under various clinical conditions. However, mini-fluid challenge has never been tested in patients with end-stage liver disease. This study investigated whether infusion of 150 ml albumin 5% can predict fluid responsiveness in cirrhotic patients following liver transplant. Methods Fifty patients receiving living donor liver transplant were included in the analysis. Mini-fluid challenge composed of 150 ml of albumin 5% administered over 1 min in three consecutive 50-ml fluid boluses. An additional 350 ml was then infused at a constant rate over 15 min (for a total of 500 ml). Stroke volume (SV) was measured as the product of the subaortic velocity time integral (VTI) and left ventricular outflow tract (LVOT) area. Fluid responsiveness was defined as an increase in SV by ≥15% after the infusion. Results Fifty patients were enrolled in the study. Fourteen patients were classified with Child A, 15 patients with Child B, and 21 patients with Child C cirrhosis. Thirty four patients were fluid responders and 16 patients were fluid non-responders. After 150 ml of albumin 5%, the SV increased significantly in our cohort. The area under receiver operating curve (AUROC) was 0.7 (95% confidence interval [CI] 0.5–0.8, P  = 0.005). In subgroup analysis, the SV increased significantly after mini fluid challenge in the Child A group ( P  = 0.017) but not Child B or C groups ( P  = 0.3 and 0.29, respectively). The AUROC for mini-fluid challenge in the Child A group was 0.86 (95% confidence interval [CI] 0.6–0.9, P  = 0.0004), while mini-fluid challenge failed to discriminate between responders and non-responders in Child B and C groups. Conclusion A mini-fluid challenge of 150 ml albumin 5% can predict fluid responsiveness in liver transplant patients with fair sensitivity and specifiicty. Subgroup analyis revealed that minifluid challenge can predict fluid responsiveness in patients with Child A cirrhosis but not patients with Child B or C cirrhosis. Trial registration NCT03396159 . (Prospective registered). Initial registration date was 10/01/2018.

Background To assess the validity of central and pulmonary veno-arterial CO 2 gradients to predict fluid responsiveness and to guide fluid management during liver transplantation. Methods In adult recipients (ASA III to IV) scheduled for liver transplantation, intraoperative fluid management was guided by pulse pressure variations (PPV). PPV of ≥15% (Fluid Responding Status-FRS) indicated fluid resuscitation with 250 ml albumin 5% boluses repeated as required to restore PPV to < 15% (Fluid non-Responding Status-FnRS). Simultaneous blood samples from central venous and pulmonary artery catheters (PAC) were sent to calculate central venous to arterial CO 2 gap [C(v-a) CO2 gap] and pulmonary venous to arterial CO 2 gap [Pulm(p-a) CO2 gap]. CO and lactate were also measured. Results Sixty seven data points were recorded (20 FRS and 47 FnRS). The discriminative ability of central and pulmonary CO 2 gaps between the two states (FRS and FnRS) was poor with AUC of ROC of 0.698 and 0.570 respectively. Central CO 2 gap was significantly higher in FRS than FnRS ( P  = 0.016), with no difference in the pulmonary CO 2 gap between both states. The central and Pulmonary CO 2 gaps are weakly correlated to PPV [r = 0.291, ( P  = 0.017) and r = 0.367, ( P  = 0.002) respectively]. There was no correlation between both CO 2 gaps and both CO and lactate. Conclusion Central and the Pulmonary CO 2 gaps cannot be used as valid tools to predict fluid responsiveness or to guide fluid management during liver transplantation. CO 2 gaps also do not correlate well with the changes in PPV or CO. Trial registration Clinicaltrials.gov Identifier: NCT03123172 . Registered on 31-march-2017.

Background The current SARS-CoV-2 pandemic may negatively impact the care of liver transplant candidates and recipients. Main body of the abstract Accordingly, each country must have its national guidelines based on the current situation and according to available tools. Liver Transplantation Scientific Committee of Waiting List Project in Egypt was established in 13 April 2020. One of the major objectives of this Scientific Committee is the preparation of national protocol for Transplant Centers in Egypt to deal with living donor liver transplantation (LDLT) during SARS-CoV-2 pandemic. Conclusions The protocol highlights basic hospital requirements for LDLT during SARS-CoV-2 pandemic, the patient selection from the waiting list, management of patients on the waiting list, and post-transplant management.

Background Bacterial translocation (BT) has been proposed as a trigger for stimulation of the immune system with consequent hemodynamic alteration in patients with liver cirrhosis. However, no information is available regarding its hemodynamic and coagulation consequences during liver transplantation. Methods We screened 30 consecutive adult patients undergoing living-donor liver transplant for the presence of BT. Bacterial DNA, Anti factor Xa (aFXa), thromboelastometry, tumor necrosis factor-α TNF-α, and interleukin-17 (IL-17) values were measured in sera before induction of anesthesia. Systemic hemodynamic data were recorded throughout the procedures. Results Bacterial DNA was detected in 10 patients (33%) (bactDNA(+)). Demographic, clinical, and hemodynamic data were similar in patients with presence or absence of bacterial DNA. BactDNA(+) patients showed significantly higher circulating values of TNF-α and IL-17, and had significantly higher clotting times and clot formation times as well as significantly lower alpha angle and maximal clot firmness than bactDNA(−) patients, P  < 0.05. We found no statistically significant difference in aFXa between the groups, P  = 0.4. Additionally, 4 patients in each group needed vasopressor agents, P  = 0.2. And, the amount of transfused blood and blood products used were similar between both groups. Conclusion Bacterial translocation was found in one-third of patients at the time of transplantation and was largely associated with increased markers of inflammation along with decreased activity of coagulation factors. Trial registration Trial Registration Number: NCT03230214 . (Retrospective registered). Initial registration date was 20/7/2017.

SARS-CoV-2 currently lacks effective first-line drug treatment. We present promising data from in silico docking studies of new Methisazone compounds (modified with calcium, Ca; iron, Fe; magnesium, Mg; manganese, Mn; or zinc, Zn) designed to bind more strongly to key proteins involved in replication of SARS-CoV-2. In this in silico molecular docking study, we investigated the inhibiting role of Methisazone and the modified drugs against SARS-CoV-2 proteins: ribonucleic acid (RNA)-dependent RNA polymerase (RdRp), spike protein, papain-like protease (PlPr), and main protease (MPro). We found that the highest binding interactions were found with the spike protein (6VYB), with the highest overall binding being observed with Mn-bound Methisazone at −8.3 kcal/mol, followed by Zn and Ca at −8.0 kcal/mol, and Fe and Mg at −7.9 kcal/mol. We also found that the metal-modified Methisazone had higher affinity for PlPr and MPro. In addition, we identified multiple binding pockets that could be singly or multiply occupied on all proteins tested. The best binding energy was with Mn–Methisazone versus spike protein, and the largest cumulative increases in binding energies were found with PlPr. We suggest that further studies are warranted to identify whether these compounds may be effective for treatment and/or prophylaxis.

The aim of this study is to evaluate the ability of cardiac output (CO) to predict 28-day mortality in patients with septic shock