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Byline: Jan J. Waele (1), F. Berrevoet (2), K. Reyntjens (3), P. Pletinckx (1), I. De laet (1), E. Hoste (1) Keywords: Intra-abdominal pressure; Intra-abdominal hypertension; Abdominal compartment syndrome; Surgery; Trauma; Critically ill patients Abstract: Objective To compare intra-abdominal pressure (IAP) measurements obtained from an intragastric Compliance catheter with the pressure measured directly in the abdominal cavity. Design and setting Prospective cohort study in an operating room of the Ghent University Hospital Patients Seven patients undergoing elective laparoscopic cholecystectomy. Interventions IAP was obtained from both an intragastric catheter and directly from the peritoneal cavity at 1-minute intervals in patients undergoing elective cholecystectomy and compared using Bland-Altman analysis. Measurements and results In 156 paired measurements obtained from 7 patients the mean difference between IAP.sub.gastric and IAP.sub.ref was 0.12a-+-a- 0.70a-mmHg (95% CI 0.01--0.23). Conclusions IAP measured using an intragastric Compliance catheter reliably reflects the reference IAP in patients undergoing laparoscopic cholecystectomy. Author Affiliation: (1) Intensive Care Unit, Ghent University Hospital, De Pintelaan 185, 9000, Gent, Belgium (2) Department of Anesthesiology, Ghent University Hospital, De Pintelaan 185, 9000, Ghent, Belgium (3) Department of Surgery, Ghent University Hospital, De Pintelaan 185, 9000, Ghent, Belgium Article History: Registration Date: 25/04/2007 Received Date: 01/03/2006 Accepted Date: 04/04/2007 Online Date: 24/05/2007 Article note: J.J. De Waele is supported by a Clinical Doctoral Grant of the Fund for Scientific Research-Flanders (Belgium F.W.O.-Vlaanderen). Electronic supplementary material The online version of this article (doi: 10.1007/s00134-007-0682-3) contains supplementary material, which is available to authorized users.

Background: Neural inertia is defined as the tendency of the central nervous system to resist transitions between arousal states. This phenomenon has been observed in mice and Drosophila anaesthetized with volatile anaesthetics: the effect-site concentration required to induce anaesthesia in 50% of the population (C50) was significantly higher than the effect-site concentration for 50% of the population to recover from anaesthesia. We evaluated this phenomenon in humans using propofol or sevoflurane (both with or without remifentanil) as anaesthetic agents.Methods: Thirty-six healthy volunteers received four sessions of anaesthesia with different drug combinations in a step-up/step-down design. Propofol or sevoflurane was administered with or without remifentanil. Serum concentrations of propofol and remifentanil were measured from arterial blood samples. Loss and return of responsiveness (LOR-ROR), response to pain (PAIN), Patient State Index (PSI) and spectral edge frequency (SEF) were modeled with NONMEM®.Results: For propofol, the C50 for induction and recovery of anaesthesia was not significantly different across the different endpoints. For sevoflurane, for all endpoints except SEF, significant differences were found. For some endpoints (LOR and PAIN) the difference was significant only when sevoflurane was combined with remifentanil.Conclusions: Our results nuance earlier findings with volatile anaesthetics in mice and Drosophila. Methodological aspects of the study, such as the measured endpoint, influence the detection of neural inertia. A more thorough definition of neural inertia, with a robust methodological framework for clinical studies is required to advance our knowledge of this phenomenon.Clinical Trial Registration: NCT 02043938. [ABSTRACT FROM AUTHOR]

Background: Dexmedetomidine, a selective α 2 -adrenoreceptor agonist, has unique characteristics, such as maintained respiratory drive and production of arousable sedation. We describe development of a pharmacokinetic-pharmacodynamic model of the sedative properties of dexmedetomidine, taking into account the effect of stimulation on its sedative properties.Methods: In a two-period, randomized study in 18 healthy volunteers, dexmedetomidine was delivered in a step-up fashion by means of target-controlled infusion using the Dyck model. Volunteers were randomized to a session without background noise and a session with pre-recorded looped operating room background noise. Exploratory pharmacokinetic-pharmacodynamic modelling and covariate analysis were conducted in NONMEM using bispectral index (BIS) monitoring of processed EEG.Results: We found that both stimulation at the time of Modified Observer's Assessment of Alertness/Sedation (MOAA/S) scale scoring and the presence or absence of ambient noise had an effect on the sedative properties of dexmedetomidine. The stimuli associated with MOAA/S scoring increased the BIS of sedated volunteers because of a transient 170% increase in the effect-site concentration necessary to reach half of the maximal effect. In contrast, volunteers deprived of ambient noise were more resistant to dexmedetomidine and required, on average, 32% higher effect-site concentrations for the same effect as subjects who were exposed to background operating room noise.Conclusions: The new pharmacokinetic-pharmacodynamic models might be used for effect-site rather than plasma concentration target-controlled infusion for dexmedetomidine in clinical practice, thereby allowing tighter control over the desired level of sedation.Clinical Trial Registration: NCT01879865. [ABSTRACT FROM AUTHOR]

Background: Dexmedetomidine, a selective α 2 -adrenoreceptor agonist, has unique characteristics, with little respiratory depression and rousability during sedations. We characterized the haemodynamic properties of dexmedetomidine by developing a pharmacokinetic-pharmacodynamic (PKPD) model with a focus on changes in mean arterial blood pressure (MAP) and heart rate.Methods: Dexmedetomidine was delivered i.v. to 18 healthy volunteers in a step-up fashion by target-controlled infusion using the Dyck model. Exploratory PKPD modelling and covariate analysis were conducted in NONMEM.Results: Our model adequately describes dexmedetomidine-induced hypotension, hypertension, and bradycardia, with a greater effective concentration for the hypertensive effect. Changes in MAP were best described by a double-sigmoidal E max model with hysteresis. Covariate analysis revealed no significant covariates apart from age on the baseline MAP in the population pharmacokinetic model used to develop this PKPD model. Simulations revealed good general agreement with published descriptive studies of haemodynamics after dexmedetomedine infusion.Conclusions: The present integrated PKPD model should allow tighter control over the desired level of sedation, while limiting potential haemodynamic side-effects.Clinical Trial Registration: NCT01879865. [ABSTRACT FROM AUTHOR]

Background: Enhanced Recovery After Surgery (ERAS) is a multimodal, evidence-based, program of care developed to minimize the response to surgical stress, associated with reduced perioperative morbidity and hospital stay. This study presents the specific ERAS Society recommendations for liver transplantation (LT) based on the best available evidence and on expert consensus., Methods: PubMed and ClinicalTrials.gov were searched in April 2019 for published and ongoing randomized clinical trials on LT in the last 15 y. Studies were selected by 5 independent reviewers and were eligible if focusing on each validated ERAS item in the area of adult LT. An e-Delphi method was used with an extended interdisciplinary panel of experts to validate the final recommendations., Results: Forty-three articles were included in the systematic review. A consensus was reached among experts after the second round. Patients should be screened for malnutrition and treated whenever possible. Prophylactic nasogastric intubation and prophylactic abdominal drainage may be omitted, and early extubation should be considered. Early oral intake, mobilization, and multimodal-balanced analgesia are recommended., Conclusions: The current ERAS recommendations were elaborated based on the best available evidence and endorsed by the e-Delphi method. Nevertheless, prospective studies need to confirm the clinical use of the suggested protocol., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Critically ill cirrhotic patients are increasingly transplanted, but there is no consensus about futile liver transplantation (LT). Therefore, the decision to delay or deny LT is often extensively debated. These debates arise from different opinions of futility among transplant team members. This study aims to achieve a multinational and multidisciplinary consensus on the definition of futility in LT and to develop well-articulated criteria for not proceeding with LT due to futility., Methods: Thirty-five international experts from anesthesiology/intensive care, hepatology, and transplant surgery were surveyed using the Delphi method. More than 70% of similar answers to a question were necessary to define agreement., Results: The panel recommended patient and graft survival at 1 year after LT to define futility. Severe frailty and persistent fever or <72 hours of appropriate antimicrobial therapy in case of ongoing sepsis were considered reasons to delay LT. A simple assessment of the number of organs failing was considered the most appropriate way to decide whether LT should be delayed or denied, with respiratory, circulatory and metabolic failures having the most influence in this decision. The thresholds of severity of organ failures contraindicating LT for which a consensus was achieved were a Pao2/FiO2 ratio<150 mm Hg, a norepinephrine dose >1 μg/kg per minute and a serum lactate level >9 mmol/L., Conclusions: Our expert panel provides a consensus on the definition of futile LT and on specific criteria for postponing or denying LT. A framework that may facilitate the decision if a patient is too sick for transplant is presented., Competing Interests: The authors declare no funding or conflicts of interest., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: Acute kidney injury is associated with high mortality in the perioperative period of liver transplantation. The aim of this position paper was to provide an up-to-date overview with special emphases on diagnosis, risk factors, and treatment., Evidence Acquisition: The Liver Intensive Care Group of Europe nominated a panel of recognized international experts who reviewed the available literature published from 1990 to January 2016 and produced clinical recommendations. The level of evidence and strength of recommendation were judged according to the Grading of Recommendations Assessment Development and Evaluation system., Evidence Synthesis: Diagnosis of AKI should be based on the KDIGO criteria. The preoperative risk factors are more related to the patient's predisposing factors and post-operative risk factors tend to be difficult to control. Therefore, focusing on intra-operative risk factors it would be important to maintain an adequate hemodynamics and to keep inferior vena cava clamping as short as possible. Biomarkers to identify AKI at an early stage are available; however, there is a lack of robust data that indicates their true beneficial effect. Intraoperative renal replacement therapy may be beneficial in some selective cases whereas its postoperative timing is still under debate., Conclusions: Perioperative liver transplant risk factors for acute kidney injury are difficult to control. Therefore, the focus should be on intra-operative hemodynamics and nephrotoxic drugs avoidance. Prospective randomized trials are needed to show the beneficial effect of early replacement therapy. In this context, the new biomarkers would be helpful in identifying kidney injury earlier.

Background: During times of organ scarcity and extended use of liver grafts, protective strategies in transplantation are gaining importance. We demonstrated in the past that volatile anesthetics such as sevoflurane attenuate ischemia-reperfusion injury during liver resection. In this randomized study, we examined if volatile anesthetics have an effect on acute graft injury and clinical outcomes after liver transplantation., Methods: Cadaveric liver transplant recipients were enrolled from January 2009 to September 2012 at 3 University Centers (Zurich/Sao Paulo/Ghent). Recipients were randomly assigned to propofol (control group) or sevoflurane anesthesia. Postoperative peak of aspartate transaminase was defined as primary endpoint, secondary endpoints were early allograft dysfunction, in-hospital complications, intensive care unit, and hospital stay., Results: Ninety-eight recipients were randomized to propofol (n = 48) or sevoflurane (n = 50). Median peak aspartate transaminase after transplantation was 925 (interquartile range, 512-3274) in the propofol and 1097 (interquartile range, 540-2633) in the sevoflurane group. In the propofol arm, 11 patients (23%) experienced early allograft dysfunction, 7 (14%) in the sevoflurane one (odds ratio, 0.64 (0.20 to 2.02, P = 0.45). There were 4 mortalities (8.3%) in the propofol and 2 (4.0%) in the sevoflurane group. Overall and major complication rates were not different. An effect on clinical outcomes was observed favoring the sevoflurane group (less severe complications), but without significance., Conclusions: This first multicenter trial comparing propofol with sevoflurane anesthesia in liver transplantation shows no difference in biochemical markers of acute organ injury and clinical outcomes between the 2 regimens. Sevoflurane has no significant added beneficial effect on ischemia-reperfusion injury compared to propofol.

Background: Perioperative hypothermia is a common complication during general anesthesia. Although rewarming of patients before surgery has been used as a preventive measure and some guidelines recommend it, the implementation of prewarming for every surgical patient is cumbersome. Therefore, we sought to determine the efficacy of two novel prewarming methods that could facilitate prewarming in daily practice., Methods: This was a prospective, randomized, multi-center, controlled study. After IRB approval and informed consent, 90 patients undergoing surgery of 30-120 min duration with general anesthesia were randomly assigned to three groups: 1) standard preoperative insulation (Group A); 2) passive preoperative insulation with a commercial prewarming suit (Group B); 3) active preoperative prewarming with a forced-air warmer connected to a prewarming suit (Group C). All patients received warmed IV fluids and intraoperative forced air warming after induction of anesthesia. Oral temperatures were recorded in the preoperative and postoperative periods. Intraoperative core temperatures were measured with an esophageal probe., Results: Repeated-measures analysis of variance (ANOVA) and post hoc Scheffé's test identified a significantly higher core temperature in the actively prewarmed group (Group C) compared to both passive groups (A, B) at 15, 30, 45, 60, and 75 min (P<0.05) after induction of anesthesia and at the end of surgery. During the first 30 min after admission at PACU, also higher oral temperatures were measured in Group C, compared with both passive insulation groups., Conclusion: In our study active prewarming with a forced-air warmer and an insulating prewarming suit achieves significantly higher core temperatures during anesthesia and at the end of surgery and avoids hypothermia at the end of surgery compared to commercial or conventional insulation techniques.

Background: As a consequence of continuous technical developments in liver surgery, laparoscopic liver resection (LLR) is increasingly performed worldwide., Methods: Between January 2004 and December 2011, 265 LLR were performed in 242 patients for various diseases. The experience of LLR is reported focusing on risk factors of conversion and their management., Results: The overall conversion rate was 17/265 (6.4%), equally distributed over the period of the study. Statistically significant factors for conversion were found to be LLR of the postero-superior (P-S) segments (SI, SIVa; SVII; SVIII) (12.7% converted versus 2.5% non-converted groups, P = 0.01) and a major compared with a minor hepatectomy (15.2% vs. 4.6%, P = 0.02 respectively). A R0 resection was achieved in 93.2% of cases. According to Dindo's classification, complications were recorded as grade I (n = 20); grade II (6); grade III (11) and grade IV(1) events (total morbidity rate of 14%). Univariate analysis identified a major hepatectomy and resection involving P-S segments as prognostic factors for conversion whereas multivariate analysis identified the latter as an independent risk factor [P = 0.003, odds ratio (OR) = 5.9, 95% confidence interval (CI) = 1.8-18.8]., Conclusions: LLR can be safely performed with low overall morbidity. According to this experience and irrespective of the learning curve, resections of P-S segments were identified as an independent risk factor for conversion in LLR., (© 2013 International Hepato-Pancreato-Biliary Association.)

Fanconi anemia (FA) is an inherited bone marrow failure syndrome due to defective DNA inter-strand cross-link repair. Hematopoietic stem cell transplantation (HSCT) is curative for pancytopenia, but may not prevent the development of non-hematological malignancies. We describe a 26-year-old male patient with FA and Marfan syndrome who in 1994 underwent successful HSCT with bone marrow stem cells from his human leukocyte antigen (HLA)-identical sister. In 2006, three lesions in the liver were detected and resected. The three lesions all showed activation of the β-catenin pathway and were histologically characterized by a highly differentiated steatotic hepatocellular carcinoma (HCC) with remnants of the underlying adenoma from which it arose, a hepatocellular adenoma with foci of well-differentiated HCC, and a cholestatic adenoma. Risk factors for the emergence of HCC included FA itself, the use of androgens for a period of 3 years preceding HSCT and toxicity of the conditioning regimen. Because of the danger of developing additional HCC, liver transplantation was proposed, taking into consideration that immunosuppression would increase the risk of other malignancies. By using part of the liver of the sister, who already acted as bone marrow donor 13 years earlier, immunosuppression could be avoided. Liver transplantation was performed in 2007 without complication. Five years after liver transplantation the patient is doing well. This case is twofold special being the first case reporting FA co-occurring with Marfan syndrome and being the first reported case of FA treated for HCC by liver transplantation from a HLA-identical sibling donor without the use of immunosuppression., (© 2013 The Japan Society of Hepatology.)

Portopulmonary hypertension (POPH), a complication of chronic liver disease, may be a contraindication to liver transplantation (LT) because of the elevated risk of peritransplant and posttransplant morbidity and mortality. Because POPH is frequently asymptomatic, screening with echocardiography is recommended. The only reliable technique, however, for diagnosing POPH is right heart catheterization (RHC). The aims of this study were to evaluate the current estimated systolic pulmonary artery pressure (sPAP) cutoff value of 30 mm Hg and to determine a better cutoff value. One hundred fifty-two patients underwent pretransplant echocardiography between January 2005 and December 2010. These echocardiographic results were compared with pulmonary artery pressures measured during the pretransplant workup or at the beginning of the transplantation procedure (both by catheterization). With a cutoff value of 30 mm Hg, 74 of the 152 patients met the criteria for POPH on echocardiography, although the diagnosis was confirmed in only 7 patients during catheterization; this resulted in a specificity of 54%. It would have been more accurate to use a cutoff value of 38 mm Hg, which had a maximal specificity of 82% and, at the same time, guaranteed a sensitivity and negative predictive value of 100%. With the incorporation of the presence or absence of right ventricular dilatation, the specificity even increased to 93% for this new cutoff value. In conclusion, the prevalence of POPH was 4.6% among LT candidates in this study. We can recommend that LT candidates with an sPAP > 38 mm Hg should be referred for RHC. With the cutoff value increased from 30 to 38 mm Hg, the number of patients undergoing invasive RHC during their evaluation could be safely reduced., (Copyright © 2013 American Association for the Study of Liver Diseases.)

Portopulmonary hypertension (POPH) is a part of group 1 pulmonary hypertension (pulmonary hypertension associated with portal hypertension). Liver transplantation (LTx) may be curative, but is usually restricted to patients with mild-to-moderate POPH. The presence of severe POPH may be a contraindication to transplantation because of the elevated risk of peritransplantation and post-transplantation morbidity and mortality. This report describes a series of seven patients with onset of moderate (two patients) or severe (five patients) POPH before LTx, of whom six were treated with oral vasodilator therapy for POPH. Although previous studies recommend aggressive parenteral prostacyclin therapy (epoprostenol), we describe the opportunity to treat cases of severe POPH with an oral phosphodiesterase type 5 inhibitor (sildenafil) and/or an endothelin receptor antagonist (bosentan/ambrisentan) as a bridge to successful LTx in selected patients.

Purpose: The aim of this study was to compare the transinguinal preperitoneal technique (TIPP) using a memory ring patch versus the Lichtenstein technique in relation to acute and chronic pain, post-operative complications and recurrence rates., Methods: During an 18-month period, all adult patients that needed treatment for a unilateral inguinal or femoral hernia were treated by the TIPP repair using the Polysoft mesh. This group was retrospectively compared with a historical cohort of patients treated by the Lichtenstein technique. Our policy concerning type of anaesthesia, post-operative pain management and visual analogue scale measurements did not change over the study period. For post-operative pain evaluation, the visual analogue scale was used (0-10) and scores were measured after 6 h, 24 h, 1 week, 1 month, 1 year and yearly thereafter. Recurrence rates were evaluated at time of clinical examinations., Results: In total, 142 patients have been analysed with the TIPP technique (group I) versus 136 patients operated in the previous 2 years with a Lichtenstein repair (group II). In group I, 112 patients (78.9%) received a medium size patch of 14 x 7.5 cm and 30 patients (21.1%) had a large patch (16 x 9 cm). The mean operative time for a TIPP procedure was statistically shorter than for a Lichtenstein repair, 33 versus 44 min, respectively (p = 0.04). After 24 h, 1 week and 1 month post-surgery, there was significantly less post-operative pain observed in the TIPP group than in the Lichtenstein group. In total, four recurrences were observed in the TIPP group (2.8%), of which one laterally and three medially. In group II, seven recurrences were observed in total (5.1%), of which five were detected within 2 years of follow-up (3.7%)., Conclusion: For surgeons performing the Lichtenstein repair but looking for modifications concerning pain relief and a quicker procedure, the TIPP approach is a feasible alternative that seems to be associated with less post-operative pain.

Unlabelled: Continuous administration of inhaled nitric oxide is now widely used as a potent and selective pulmonary vasodilator. We have evaluated the effects of IV dipyridamole, a cyclic guanosine monophosphate (cGMP) phosphodiesterase inhibitor, on the magnitude and duration of action of inhaled nitric oxide (NO)-mediated pulmonary vasodilation. We hypothesized that inhibition of cGMP degradation could augment and prolong the pulmonary vasodilating effects of NO and allow for intermittent NO inhalation. In eight anesthetized and mechanically ventilated piglets, IV U-46619, a thromboxane A(2) analog, was used to induce pulmonary hypertension. The effects of 2, 5, and 10 ppm of NO, delivered during 4 min for each concentration and followed by a 10-min NO-free interval after each NO concentration, were evaluated without and with dipyridamole. Pulmonary vascular resistance decreased from 825 +/- 49 dynes. s. cm(-5) (U-46619) to 533 +/- 48 dynes. s. cm(-5) (10 ppm NO) (P < 0.05 versus U-46619) and 396 +/- 42 dynes. s. cm(-5) (dipyridamole 10 microg kg-1x min-1 and 10 ppm NO) (P <0.05 versus NO), and cardiac output increased from 1.93 +/- 0.09 L/min to 2.03 +/- 0.13 L/min and 2.60 +/- 0.30 L/min (P < 0.05 versus NO). Mean arterial blood pressure decreased from 90 +/- 5 mm Hg (10 ppm NO) to 75 +/- 3 mm Hg (dipyridamole plus 10 ppm NO) (P < 0.01). The pulmonary vasodilation obtained with NO alone could be prolonged from 12 to 42 min when inhaled NO was combined with IV dipyridamole, accounting for a time-weighted reduction in NO exposure by 72%. We conclude that dipyridamole augments the effects of NO on right ventricular afterload, allows for intermittent NO inhalation, and can significantly reduce exposure to NO., Implications: IV dipyridamole prolongs the action of inhaled nitric oxide (NO) in a piglet model of acute pulmonary hypertension. Intermittent NO inhalation combined with IV dipyridamole decreases pulmonary artery pressure for a prolonged period of time and reduces exposure to NO.

Inhaled nitric oxide (NO) is increasingly used in the treatment of pulmonary hypertension, despite its potential toxicity and the risk of life-threatening rebound pulmonary hypertension upon its discontinuation. We investigated whether i.v. dipyridamole, a cGMP phosphodiesterase inhibitor, increased the effects of inhaled NO and prevented rebound pulmonary hypertension. In 14 anesthetized and mechanically ventilated piglets, pulmonary hypertension was induced with U-46619, a thromboxane A(2) analogue. Response to NO and rebound pulmonary hypertension were evaluated without and with i.v. dipyridamole. Low-dose dipyridamole (10 micro g/kg/min) increased cardiac output and augmented the effects of inhaled NO on pulmonary vascular resistance, with marginal additive effect on mean pulmonary artery pressure. Pulmonary vascular resistance decreased from 904 to 511 (20 parts per million NO) (p < 0.0005) and 358 dyne s cm(-5) (20 parts per million NO + dipyridamole) (p < 0.001 versus NO alone), and mean pulmonary artery pressure decreased from 29.0 to 20.5 (p < 0.0001) and 19.3 mm Hg (NS versus NO), respectively. Mean arterial pressure decreased from 85 to 74 mm Hg (dipyridamole + NO) (p < 0.01). High-dose dipyridamole (100 micro g/kg/min) with inhaled NO reduced pulmonary vascular resistance to 334 dyne s cm(-5) but also decreased mean arterial pressure to 57 mm Hg. Eight piglets developed rebound pulmonary hypertension. Two died of acute right ventricular failure and, in five, rebound pulmonary hypertension was prevented by low-dose dipyridamole. In conclusion, low-dose i.v. dipyridamole augments the effects of inhaled NO on right ventricular afterload with moderate changes in systemic hemodynamics, and can prevent rebound pulmonary hypertension.

The efficiency of two types of steroid treatment was assessed in primary intracerebral haemorrhages. No significant difference in clinical evolution was observed between 57 cases treated with dexamethasone, 28 cases with methylprednisolone and 44 cases without corticosteroids. In a subgroup of 46 patients with putamino-capsular bleedings the non-steroid-treated group did significantly better than the steroid-treated one. Adverse reactions occurred at the same rate in the three groups.