Cerebral perfusion and metabolism with mild hypercapnia vs. normocapnia in a porcine post cardiac arrest model with and without targeted temperature management.

Aim: To determine whether targeting mild hypercapnia (PaCO2 7 kPa) would yield improved cerebral blood flow and metabolism compared to normocapnia (PaCO2 5 kPa) with and without targeted temperature management to 33 °C (TTM33) in a porcine post-cardiac arrest model. Methods: 39 pigs were resuscitated after 10 minutes of cardiac arrest using cardiopulmonary bypass and randomised to TTM33 or no-TTM, and hypercapnia or normocapnia. TTM33 was managed with intravasal cooling. Animals were stabilized for 30 minutes followed by a two-hour intervention period. Hemodynamic parameters were measured continuously, and neuromonitoring included intracranial pressure (ICP), pressure reactivity index, cerebral blood flow, brain-tissue pCO2 and microdialysis. Measurements are reported as proportion of baseline, and areas under the curve during the 120 min intervention period were compared. Results: Hypercapnia increased cerebral flow in both TTM33 and no-TTM groups, but also increased ICP (199% vs. 183% of baseline, p = 0.018) and reduced cerebral perfusion pressure (70% vs. 84% of baseline, p < 0.001) in no-TTM animals. Cerebral lactate (196% vs. 297% of baseline, p < 0.001), pyruvate (118% vs. 152% of baseline, p < 0.001), glycerol and lactate/pyruvate ratios were lower with hypercapnia in the TTM33 group, but only pyruvate (133% vs. 150% of baseline, p = 0.002) was lower with hypercapnia among no-TTM animals. Conclusion: In this porcine post-arrest model, hypercapnia led to increased cerebral flow both with and without hypothermia, but also increased ICP and reduced cerebral perfusion pressure in no-TTM animals. The effects of hypercapnia were different with and without TTM.(Institutional protocol number: FOTS, id 14931).

Haemodynamic effects of remifentanil during induction of general anaesthesia with propofol. A randomised trial.

BACKGROUND: Remifentanil may have a dose-dependent haemodynamic effect during the induction of general anaesthesia combined with propofol. Our objective was to investigate whether systolic arterial blood pressure (SAP) was reduced to a greater extent when the remifentanil dose was increased. METHODS: This randomised, double-blind, dose-controlled study was conducted at the Day Surgery Unit of Haugesund Hospital, Norway. Ninety-nine healthy women scheduled for gynaecological surgery were randomly allocated in a 1:1:1 ratio to receive remifentanil induction with a low, medium or high dose corresponding to maximum effect-site concentrations (Ce) of 2, 4 and 8 ng/mL. The induction dose of propofol was 1.8 mg/kg, with a Ce of 2.9 µg/mL. Anaesthesia was induced using target-controlled infusion. After 150 s of sedation, a bolus of remifentanil and propofol was administered. Baseline was defined as 55-5 s before the bolus dose, and the total observation time was 450 s. We used beat-to-beat haemodynamic monitoring with LiDCOplus. The primary outcome variable was the maximum decrease in SAP within 5 min after bolus administration of remifentanil and propofol. Absolute and relative changes from baseline to minimal values and the area under the curve (AUC) were used as effect measures. Comparisons of groups were performed using analysis of variance (ANOVA). RESULTS: Median remifentanil doses were 0.75, 1.5 and 3.0 µg/kg in the low-, medium- and high-dose groups, respectively. The absolute changes (mean ± standard deviation) in SAP in the low-, medium- and high-dose groups of remifentanil were -39 ± 9.6 versus -43 ± 9.1, and -41 ± 10 mmHg, respectively. No difference (95% confidence interval) in the absolute change in SAP was observed between the groups (ANOVA, p = .29); medium versus low dose 3.7 (-2.0, 9.4) mmHg, and high versus medium dose -2.2 (-8.0; 3.5) mmHg. The relative changes from baseline to minimum SAP values were -30% versus -32% versus -32% (p = .52). The between-group differences in the AUC were not statistically significant. Relative changes in heart rate (-20% vs. -21% vs. -21%), stroke volume (-19% vs. -16% vs. -16%), cardiac output (-32% vs. -32% vs. -32%), systemic vascular resistance (-24% vs. -27% vs. -28%), and AUC were not statistically significant. CONCLUSION: This trial demonstrated major haemodynamic changes during the induction of anaesthesia with remifentanil and propofol. However, we did not observe any statistically significant differences between low, medium or high doses of remifentanil when using continuous invasive high-accuracy beat-to-beat monitoring.

Local Postoperative Graft Inflammation in Pancreas Transplant Patients With Early Graft Thrombosis.

Background: Graft thrombosis is the main cause of early graft loss following pancreas transplantation, and is more frequent in pancreas transplant alone (PTA) compared with simultaneous pancreas-kidney (SPK) recipients. Ischemia-reperfusion injury during transplantation triggers a local thromboinflammatory response. We aimed to evaluate local graft inflammation and its potential association with early graft thrombosis. Methods: In this observational study, we monitored 67 pancreas-transplanted patients using microdialysis catheters placed on the pancreatic surface during the first postoperative week. We analyzed 6 cytokines, interleukin-1 receptor antagonist (IL-1ra), IL-6, IL-8, interferon gamma-induced protein 10 (IP-10), macrophage inflammatory protein 1ß (MIP-1ß), IL-10, and the complement activation product complement activation product 5a (C5a) in microdialysis fluid. We compared the dynamic courses between patients with pancreas graft thrombosis and patients without early complications (event-free) and between PTA and SPK recipients. Levels of the local inflammatory markers, and plasma markers C-reactive protein, pancreas amylase, and lipase were evaluated on the day of thrombosis diagnosis compared with the first week in event-free patients. Results: IL-10 and C5a were not detectable. Patients with no early complications (n = 34) demonstrated high IL-1ra, IL-6, IL-8, IP-10, and MIP-1ß concentrations immediately after surgery, which decreased to steady low levels during the first 2 postoperative days (PODs). Patients with early graft thrombosis (n = 17) demonstrated elevated IL-6 (P = 0.003) concentrations from POD 1 and elevated IL-8 (P = 0.027) concentrations from POD 2 and throughout the first postoperative week compared with patients without complications. IL-6 (P < 0.001) and IL-8 (P = 0.003) were higher on the day of thrombosis diagnosis compared with patients without early complications. No differences between PTA (n = 35) and SPK (n = 32) recipients were detected. Conclusions: Local pancreas graft inflammation was increased in patients experiencing graft thrombosis, with elevated postoperative IL-6 and IL-8 concentrations, but did not differ between PTA and SPK recipients. Investigating the relationship between the local cytokine response and the formation of graft thrombosis warrants further research.

Hemodynamic effects of a low versus a high dose of propofol during induction of anesthesia. A randomized trial.

BACKGROUND: Hypotension is common after anesthesia induction with propofol and is associated with increased morbidity. It is important to examine the effects of the proposed interventions to limit preventable hypotension, as suggested by the reduction in the dose of propofol. Our objective was to investigate whether a high dose of propofol is inferior to a low dose with respect to changes in systolic arterial blood pressure (SAP). METHODS: This randomized, double-blind, dose-controlled, non-inferiority study included 68 healthy women scheduled for gynecological surgery at the Day Surgery Unit, Haugesund Hospital, Norway. The patients were randomly allocated 1:1 to a low or high dose (1.4 mg/kg total body weight (TBW) versus 2.7 mg/kg TBW of propofol corresponding to maximal effect site concentrations (Ce) of 2.0 µg/mL versus 4.0 µg/mL. The dose of remifentanil was 1.9-2.0 µg/kg TBW, with maximal Ce of 5.0 ng/mL. The patients were observed for 450 s from the start of the infusions. The first 150 s was the sedation period, after which a bolus of propofol and remifentanil was administered. Baseline was defined as 55-5 s before the bolus doses. LiDCOplus was used for invasive beat-to-beat hemodynamic monitoring of changes in SAP, heart rate (HR), cardiac output (CO), stroke volume (SV), and systemic vascular resistance (SVR). A difference of 10 mmHg in the change in SAP was considered to be clinically important. RESULTS: The SAP change difference for low versus high dose was -2.9 mmHg (95% CI -9.0-3.1). The relative changes for low versus high dose were SAP -31% versus -36%, (p < .01); HR -24% versus -20%, (p = .09); SVR -20% versus -31%, (p < .001); SV -16% versus -20%, (p = .04); and CO -35% versus -32%, (p = .33). CONCLUSION: A high dose of propofol was not inferior to a low dose, and a reduction in the dose of propofol did not result in clinically important attenuation of major hemodynamic changes during induction in healthy women. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT03861364, January 3, 2019.

Thromboinflammatory response is increased in pancreas transplant alone versus simultaneous pancreas-kidney transplantation and early pancreas graft thrombosis is associated with complement activation.

Background: Pancreas transplant alone (PTA) recipients are more affected by pancreas graft thrombosis, and graft loss compared to simultaneous pancreas-kidney (SPK) recipients. The pathophysiology is unknown, but an increased immune response has been suggested in the PTA recipients. In this observational study, we compared perioperative thromboinflammation between PTA (n=32) and SPK (n=35) recipients, and between PTA recipients with (n=14) versus without (n=18) early graft thrombosis. Methods: We measured C-reactive protein (CRP), plasma markers of activated coagulation and complement, and cytokines preoperatively and daily during the first postoperative week. Results: Preoperatively, coagulation and complement activation markers were comparable between PTA and SPK recipients, while cytokine concentrations were higher in SPK recipients (TNF, IL-8, IP-10, MCP-1, MIP-1α; all p<0.05). On the first postoperative day, PTA recipients had higher coagulation activation, measured as thrombin-antithrombin complex (TAT), than SPK recipients (p=0.008). In the first postoperative week, PTA recipients showed higher relative cytokine release (IL-6, IL-8, G-CSF, IP-10, MCP-1, and MIP-1α; all p<0.05) while SPK recipients showed higher absolute cytokine concentrations (TNF, IL-1ra, IL-8, MIP-1α, and IL-4; all p<0.05). PTA and SPK recipients showed similar terminal complement complex (TCC, sC5b-9) activation. On the first postoperative day, TCC (OR 1.2 [95% CI 1.0-1.5] for 0.1 CAU/ml increase, p=0.02) and CRP (OR 1.2 [95% CI 1.0-1.3] for 10 mg/L increase, p=0.04) were associated with an increased risk of early graft thrombosis. TCC was specific for graft thrombosis, while CRP increased with several complications. PTA recipients with compared to those without graft thrombosis had higher TCC pre- (p=0.04) and postoperatively (p=0.03). Conclusion: The relative increase in postoperative thromboinflammatory response was more pronounced in PTA recipients. Complement activation was associated with an increased risk of graft thrombosis. This study indicates that innate immune activation rather than elevated levels may affect early postoperative pancreas graft thrombosis. Clinical trial registration: https://clinicaltrials.gov/ct2/show/NCT01957696, identifier NCT01957696.

Assessment of Intestinal Ischemia-Reperfusion Injury Using Diffuse Reflectance VIS-NIR Spectroscopy and Histology.

A porcine model was used to investigate the feasibility of using VIS-NIR spectroscopy to differentiate between degrees of ischemia-reperfusion injury in the small intestine. Ten pigs were used in this study and four segments were created in the small intestine of each pig: (1) control, (2) full arterial and venous mesenteric occlusion for 8 h, (3) arterial and venous mesenteric occlusion for 2 h followed by reperfusion for 6 h, and (4) arterial and venous mesenteric occlusion for 4 h followed by reperfusion for 4 h. Two models were built using partial least square discriminant analysis. The first model was able to differentiate between the control, ischemic, and reperfused intestinal segments with an average accuracy of 99.2% with 10-fold cross-validation, and the second model was able to discriminate between the viable versus non-viable intestinal segments with an average accuracy of 96.0% using 10-fold cross-validation. Moreover, histopathology was used to investigate the borderline between viable and non-viable intestinal segments. The VIS-NIR spectroscopy method together with a PLS-DA model showed promising results and appears to be well-suited as a potentially real-time intraoperative method for assessing intestinal ischemia-reperfusion injury, due to its easy-to-use and non-invasive nature.

Utilization of dielectric properties for assessment of liver ischemia-reperfusion injury in vivo and during machine perfusion.

There is a shortage of donor livers and patients consequently die on waiting lists worldwide. Livers are discarded if they are clinically judged to have a high risk of non-function following transplantation. With the aim of extending the pool of available donor livers, we assessed the condition of porcine livers by monitoring the microwave dielectric properties. A total of 21 livers were divided into three groups: control with no injury (CON), biliary injury by hepatic artery occlusion (AHEP), and overall hepatic injury by static cold storage (SCS). All were monitored for four hours in vivo, followed by ex vivo plurithermic machine perfusion (PMP). Permittivity data was modeled with a two-pole Cole-Cole equation, and dielectric properties from one-hour intervals were analyzed during in vivo and normothermic machine perfusion (NMP). A clear increasing trend in the conductivity was observed in vivo in the AHEP livers compared to the control livers. After four hours of NMP, separations in the conductivity were observed between the three groups. Our results indicate that dielectric relaxation spectroscopy (DRS) can be used to detect and differentiate liver injuries, opening for a standardized and reliable point of evaluation for livers prior to transplantation.

Small intestinal viability assessment using dielectric relaxation spectroscopy and deep learning.

Intestinal ischemia is a serious condition where the surgeon often has to make important but difficult decisions regarding resections and resection margins. Previous studies have shown that 3 h (hours) of warm full ischemia of the small bowel followed by reperfusion appears to be the upper limit for viability in the porcine mesenteric ischemia model. However, the critical transition between 3 to 4 h of ischemic injury can be nearly impossible to distinguish intraoperatively based on standard clinical methods. In this study, permittivity data from porcine intestine was used to analyze the characteristics of various degrees of ischemia/reperfusion injury. Our results show that dielectric relaxation spectroscopy can be used to assess intestinal viability. The dielectric constant and conductivity showed clear differences between healthy, ischemic and reperfused intestinal segments. This indicates that dielectric parameters can be used to characterize different intestinal conditions. In addition, machine learning models were employed to classify viable and non-viable segments based on frequency dependent dielectric properties of the intestinal tissue, providing a method for fast and accurate intraoperative surgical decision-making. An average classification accuracy of 98.7% was obtained using only permittivity data measured during ischemia, and 96.2% was obtained with data measured during reperfusion. The proposed approach allows the surgeon to get accurate evaluation from the trained machine learning model by performing one single measurement on an intestinal segment where the viability state is questionable.

Microdialysis and CO2 sensors detect pancreatic ischemia in a porcine model.

BACKGROUND: Pancreatic transplantation is associated with a high rate of early postoperative graft thrombosis. If a thrombosis is detected in time, a potentially graft-saving intervention can be initiated. Current postoperative monitoring lacks tools for early detection of ischemia. The aim of this study was to investigate if microdialysis and tissue pCO2 sensors detect pancreatic ischemia and whether intraparenchymal and organ surface measurements are comparable. METHODS: In 8 anaesthetized pigs, pairs of lactate monitoring microdialysis catheters and tissue pCO2 sensors were simultaneously inserted into the parenchyma and attached to the surface of the pancreas. Ischemia was induced by sequential arterial and venous occlusions of 45-minute duration, with two-hour reperfusion after each occlusion. Microdialysate was analyzed every 15 minutes. Tissue pCO2 was measured continuously. We investigated how surface and parenchymal measurements correlated and the capability of lactate and pCO2 to discriminate ischemic from non-ischemic periods. RESULTS: Ischemia was successfully induced by arterial occlusion in 8 animals and by venous occlusion in 5. During all ischemic episodes, lactate increased with a fold change of 3.2-9.5 (range) in the parenchyma and 1.7-7.6 on the surface. Tissue pCO2 increased with a fold change of 1.6-3.5 in the parenchyma and 1.3-3.0 on the surface. Systemic lactate and pCO2 remained unchanged. The area under curve (AUC) for lactate was 0.97 (95% confidence interval (CI) 0.93-1.00) for parenchymal and 0.90 (0.83-0.97) for surface (p<0.001 for both). For pCO2 the AUC was 0.93 (0.89-0.96) for parenchymal and 0.85 (0.81-0.90) for surface (p<0.001 for both). The median correlation coefficients between parenchyma and surface were 0.90 (interquartile range (IQR) 0.77-0.95) for lactate and 0.93 (0.89-0.97) for pCO2. CONCLUSIONS: Local organ monitoring with microdialysis and tissue pCO2 sensors detect pancreatic ischemia with adequate correlation between surface and parenchymal measurements. Both techniques and locations seem feasible for further development of clinical pancreas monitoring.

Validating the US pancreas donor risk index in a Norwegian population, a retrospective observational study.

OBJECTIVES: Despite advances in immunosuppression and surgical technique, pancreas transplantation is still associated with a significant graft loss rate. The Pancreas Donor Risk Index (PDRI) is a pre-transplant scoring tool derived from a US population. We sought to validate the PDRI in a Norwegian population. METHODS: We retrospectively retrieved donor data for 344 pancreas transplants undertaken in Norway between 2000 and 2019, utilising the Scandiatransplant database, and matched these to the respective recipients. The PDRI score was calculated for each transplanted pancreas, these were then stratified into quintiles. The association between the PDRI quintiles and 1-year graft survival was calculated, and this was repeated for the different types of pancreas transplantation. The association between PDRI as a continuous variable, and graft survival was determined. Donor and recipient data were compared to the original US population. RESULTS: The overall 1-year graft survival was 82.7%. There were no significant differences in survival between the different PDRI quintiles. When viewed as a continuous variable, increased PDRI score was not associated with decreased graft survival. Significant differences between the Norwegian and US populations were found. CONCLUSIONS: When applied to a Norwegian population, the PDRI score was unable to predict 1-year graft survival.

Early detection of anastomotic leakage after pancreatoduodenectomy with microdialysis catheters: an observational Study.

BACKGROUND: Microdialysis catheters can detect focal inflammation and ischemia, and thereby have a potential for early detection of anastomotic leakages after pancreatoduodenectomy. The aim was to investigate whether microdialysis catheters placed near the pancreaticojejunostomy can detect leakage earlier than the current standard of care. METHODS: Thirty-five patients with a median age 69 years were included. Two microdialysis catheters were placed at the end of surgery; one at the pancreaticojejunostomy, and one at the hepaticojejunostomy. Concentrations of glucose, lactate, pyruvate, and glycerol were analyzed hourly in the microdialysate during the first 24 h, and every 2-4 h thereafter. RESULTS: Seven patients with postoperative pancreatic fistulae (POPF) had significantly higher glycerol levels (P < 0.01) in the microdialysate already in the first postoperative samples. Glycerol concentrations >400 µmol/L during the first 12 postoperative hours detected patients with POPF with a sensitivity of 100% and a specificity of 93% (P < 0.001). After 24 h, lactate and lactate-to-pyruvate ratio were significantly higher (P < 0.05) and glucose was significantly lower (P < 0.05) in patients with POPF. CONCLUSION: High levels of glycerol in microdialysate was an early detector of POPF. The subsequent inflammation was detected as increase in lactate and lactate-to-pyruvate ratio and a decrease in glucose (NCT03627559).

Quantification of aerosol dispersal from suspected aerosol-generating procedures.

BACKGROUND: Oxygen-delivering modalities like humidified high-flow nasal cannula (HFNC) and noninvasive positive-pressure ventilation (NIV) are suspected of generating aerosols that may contribute to transmission of disease such as coronavirus disease 2019. We sought to assess if these modalities lead to increased aerosol dispersal compared to the use of non-humidified low-flow nasal cannula oxygen treatment (LFNC). METHODS: Aerosol dispersal from 20 healthy volunteers using HFNC, LFNC and NIV oxygen treatment was measured in a controlled chamber. We investigated effects related to coughing and using a surgical face mask in combination with the oxygen delivering modalities. An aerodynamic particle sizer measured aerosol particles (APS3321, 0.3-20 µm) directly in front of the subjects, while a mesh of smaller particle sensors (SPS30, 0.3-10 µm) was distributed in the test chamber. RESULTS: Non-productive coughing led to significant increases in particle dispersal close to the face when using LFNC and HFNC but not when using NIV. HFNC or NIV did not lead to a statistically significant increase in aerosol dispersal compared to LFNC. With non-productive cough in a room without air changes, there was a significant drop in particle levels between 100 cm and 180 cm from the subjects. CONCLUSIONS: Our results indicate that using HFNC and NIV does not lead to increased aerosol dispersal compared to low-flow oxygen treatment, except in rare cases. For a subject with non-productive cough, NIV with double-limb circuit and non-vented mask may be a favourable choice to reduce the risk for aerosol spread.

Assessing Ischemic Injury in Human Intestine Ex Vivo with Electrical Impedance Spectroscopy.

Electrical impedance spectroscopy is a well-established tool for monitoring changes in the electrical properties of tissue. Most tissue and organ types have been investigated in various studies. As for the small intestine, there are several published studies conducted on pig and rat models. This study investigates the changes in passive electrical properties of the complete wall of the human intestine non-invasively during ischemia. We aim to use the passive electrical properties to assess intestinal viability. The bioimpedance measurements were performed using a two-electrode set-up with a Solartron 1260 Impedance/gain-phase analyser. The small intestinal samples were resected from patients who underwent pancreaticoduodenectomy. Impedance measurements were conducted following resection by placing the electrodes on the surface of the intestine. A voltage was applied across the intestinal sample and the measured electrical impedance was obtained in the ZPlot software. Impedance data were further fitted into a Cole model to obtain the Cole parameters. The Py value was calculated from the extracted Cole parameters and used to assess the cell membrane integrity, thus evaluate the intestinal viability. Eight small intestinal segments from different patients were used in this study and impedance measurements were performed once an hour for a ten-hour period. One hour after resection, the impedance decreased, then increased the next two hours, before decreasing until the end of the experiment. For all the intestinal segments, the Py values first increased and reached a plateau which lasted for 1 - 2 hours, before it decreased irreversibly. The time interval where Py value reached the maximum is consistent with reported viable/non-viable limits from histological analysis.

Automatic Prediction of Ischemia-Reperfusion Injury of Small Intestine Using Convolutional Neural Networks: A Pilot Study.

Acute intestinal ischemia is a life-threatening condition. The current gold standard, with evaluation based on visual and tactile sensation, has low specificity. In this study, we explore the feasibility of using machine learning models on images of the intestine, to assess small intestinal viability. A digital microscope was used to acquire images of the jejunum in 10 pigs. Ischemic segments were created by local clamping (approximately 30 cm in width) of small arteries and veins in the mesentery and reperfusion was initiated by releasing the clamps. A series of images were acquired once an hour on the surface of each of the segments. The convolutional neural network (CNN) has previously been used to classify medical images, while knowledge is lacking whether CNNs have potential to classify ischemia-reperfusion injury on the small intestine. We compared how different deep learning models perform for this task. Moreover, the Shapley additive explanations (SHAP) method within explainable artificial intelligence (AI) was used to identify features that the model utilizes as important in classification of different ischemic injury degrees. To be able to assess to what extent we can trust our deep learning model decisions is critical in a clinical setting. A probabilistic model Bayesian CNN was implemented to estimate the model uncertainty which provides a confidence measure of our model decisions.

Cerebral perfusion and metabolism with mean arterial pressure 90 vs. 60 mmHg in a porcine post cardiac arrest model with and without targeted temperature management.

AIM: To determine whether targeting a mean arterial pressure of 90 mmHg (MAP90) would yield improved cerebral blood flow and less ischaemia compared to MAP 60 mmHg (MAP60) with and without targeted temperature management at 33 °C (TTM33) in a porcine post-cardiac arrest model. METHODS: After 10 min of cardiac arrest, 41 swine of either sex were resuscitated until return of spontaneous circulation (ROSC). They were randomised to TTM33 or no-TTM, and MAP60 or MAP90; yielding four groups. Temperatures were managed with intravasal cooling and blood pressure targets with noradrenaline, vasopressin and nitroprusside, as appropriate. After 30 min of stabilisation, animals were observed for two hours. Cerebral perfusion pressure (CPP), cerebral blood flow (CBF), pressure reactivity index (PRx), brain tissue pCO2 (PbtCO2) and tissue intermediary metabolites were measured continuously and compared using mixed models. RESULTS: Animals randomised to MAP90 had higher CPP (p < 0.001 for both no-TTM and TTM33) and CBF (no-TTM, p < 0.03; TH, p < 0.001) compared to MAP60 during the 150 min observational period post-ROSC. We also observed higher lactate and pyruvate in MAP60 irrespective of temperature, but no significant differences in PbtCO2 and lactate/pyruvate-ratio. We found lower PRx (indicating more intact autoregulation) in MAP90 vs. MAP60 (no-TTM, p = 0.04; TTM33, p = 0.03). CONCLUSION: In this porcine cardiac arrest model, targeting MAP90 led to better cerebral perfusion and more intact autoregulation, but without clear differences in ischaemic markers, compared to MAP60. INSTITUTIONAL PROTOCOL NUMBER: FOTS, id 8442.

Monitoring of patients with microdialysis following pancreaticoduodenectomy-the MINIMUM study: study protocol for a randomized controlled trial.

BACKGROUND: Postoperative pancreatic fistula after pancreatoduodenectomy is a much-feared complication associated with substantial mortality and morbidity. The current standard for diagnosing postoperative pancreatic fistula, besides routine clinical examination, include radiological examinations, analysis of pancreatic drain amylase activity, and routine blood samples. Another promising method is by intraperitoneal microdialysis to monitor intraperitoneal metabolites measured at the pancreaticojejunostomy, thereby detecting what occurs locally, before chemical events can be reflected as measurable changes in systemic blood levels. METHODS: The MINIMUM study is a prospective, randomized, controlled, single center enrolling 200 patients scheduled for open pancreatoduodenectomy comparing the microdialysis method to the "standard of care." Half of the included patients will be randomized to receive an intraperitoneal microdialysis catheter implanted at the end of surgery and will be monitored by microdialysis as an additional monitoring tool. The other half of the patients will not receive a microdialysis catheter and will be monitored according to the current standard of care. The primary objective is to evaluate if the microdialysis method can reduce the total length of stay at the hospital. Secondary endpoints are the frequency of complications, length of stay at the hospital at our institution, catheter malfunction, number of infections and bleeding episodes caused by the microdialysis catheter, patient-reported quality of life and pain, and cost per patient undergoing pancreatoduodenectomy. The patients will be randomized in a 1:1 ratio. DISCUSSION: Intraabdominal microdialysis could potentially reduce morbidity and mortality after pancreatoduodenectomy. Furthermore, there is a great potential for shortening the in-hospital length of stay and reducing the financial aspect considerably. This study may potentially open the possibility for using microdialysis as standard monitoring in patients undergoing pancreatoduodenectomy. The hypothesis is that the microdialysis method compared to "standard care" will reduce the total length of hospital stay. TRIAL REGISTRATION: Clinicaltrials.gov ( NCT03631173 ). Registered on 7 September 2018 under the name: "Monitoring of patients With Microdialysis Following Pancreaticoduodenectomy". Based on protocol version 19-1, dated 15th January 2019.

Ethyl pyruvate supplemented in drinking water ameliorates experimental nonalcoholic steatohepatitis.

Inflammation and oxidative stress play a significant role in the pathogenesis of nonalcoholic steatohepatitis (NASH). Ethyl pyruvate (EP) is a novel anti-inflammatory agent and a potent reactive oxygen species (ROS) scavenger. Therefore, EP supplemented in drinking water may alleviate experimental NASH in this study (even though 0.3% of EP cannot attenuate the simple non-aggressive fatty liver). The methionine-choline-deficient (MCD) diet was given to the C57BL/6 male mice for 3 weeks to induce NASH. The NASH animals were randomized into 3 treatment groups: animals in the MCD alone group were treated with normal drinking water alone; animals in the delayed EP group were given 3% (v/v) of EP supplemented in normal drinking water, the treatment started 10 days after MCD diet feeding; animals in the early EP therapy group were treated the same as the delayed EP group except that EP treatment started the same day when MCD diet was given; the control mice were fed with normal chow and treated with normal drinking water (n = 10 for each group). Compared to MCD group with normal drinking water, early EP treatment significantly decreased serum ALT and improved NASH histopathology; delayed EP therapy only attenuated NASH in 50% (5/10) of the animals. The beneficial effects were associated with decreased hepatic TNF-a and IL-6 mRNA expression on early 5 days, inhibited NF-kB activation, reduced liver tissue malondialdehyde levels, and decreased intestinal bacterial translocation (BT). In conclusion: EP supplemented in drinking water attenuates experimental NASH.

Early detection of complications in pancreas transplants by microdialysis catheters, an observational feasibility study.

BACKGROUND: Despite advances in immunosuppression and surgical technique, pancreas transplantation is encumbered with a high rate of complication and graft losses. Particularly, venous graft thrombi occur relatively frequently and are rarely detected before the transplant is irreversibly damaged. METHODS: To detect complications early, when the grafts are potentially salvageable, we placed microdialysis catheters anteriorly and posteriorly to the graft in a cohort of 34 consecutive patients. Glucose, lactate, pyruvate, and glycerol were measured at the bedside every 1-2 hours. RESULTS: Nine patients with graft venous thrombosis had significant lactate and lactate-to-pyruvate-ratio increases without concomitant rise in blood glucose or clinical symptoms. The median lactate in these patients was significantly higher in both catheters compared to non-events (n = 15). Out of the nine thrombi, four grafts underwent successful angiographic extraction, one did not require intervention and four grafts were irreversibly damaged and explanted. Four patients with enteric anastomosis leakages had significantly higher glycerol measurements compared to non-events. As with the venous thrombi, lactate and lactate-to-pyruvate ratio were also increased in six patients with graft surrounding hematomas. CONCLUSIONS: Bedside monitoring with microdialysis catheters is a promising surveillance modality of pancreatic grafts, but differentiating between the various pathologies proves challenging.

Thoracic Epidural Analgesia for Postoperative Pain Management in Liver Transplantation: A 10-year Study on 685 Liver Transplant Recipients.

BACKGROUND: Thoracic epidural analgesia (TEA) is not widely used for postoperative pain management in liver transplantation due to hepatic coagulopathy-related increased risk of inducing an epidural hematoma. However, an increasing number of patients are transplanted for other indications than the end-stage liver disease and without coagulopathy allowing insertion of an epidural catheter. METHODS: This study is a retrospective observational single-center study of all adult patients undergoing first-time liver transplantation at Oslo University Hospital between January 1, 2008, and December 31, 2017. Data regarding patient characteristics were obtained from the Nordic liver transplant registry, medical records, and pain registration forms. Patients without coagulopathy (international normalized ratio <1.5 and platelets >100 × 109/L) were eligible for TEA. RESULTS: Out of 685 first-time liver transplantations in a 10-year period, 327 received TEA, and 358 did not. The median Model of End-stage Liver Disease score was lower in the TEA group than in the non-TEA-group (9 versus 17, P < 0.001), and fewer patients were hospitalized preoperatively (16 versus 127, P < 0.001). The median international normalized ratio (1.1 versus 1.6, P < 0.001) and platelet count (190 versus 78, P < 0.001) were different between the TEA and non-TEA groups. There were no serious complications related to insertion or removal of the TEA catheters. Patients in the TEA group had less pain with a mean numeric rating scale at postoperative days 0-5 of 1.4 versus 1.8 (P = 0.008). Nearly 50% of the patients were prescribed opioids when discharged from hospital (non-TEA 154 versus TEA 158, P = 0.23), and there was no difference after 1 year (P = 0.718). CONCLUSIONS: Our report revealed very good pain control with both TEA and the non-TEA modality. TEA was without any serious complications like epidural hematoma or infection/abscess in selected liver transplant recipients without severe coagulopathy. Opioid prescription at hospital discharge and by 1-year follow-up did not differ between the groups.