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Circulating cardiac biomarkers may improve the prediction of long-term outcomes after cardiac surgery. The authors sought to assess if cardiac biomarkers also help better predict short-term morbidity.Prospective observational study.Single academic hospital.A total of 250 patients undergoing aortic or mitral valve surgery with or without associated coronary artery bypass grafts.None MEASUREMENT AND MAIN RESULTS: Relationships between preoperative plasma concentrations of four cardiac biomarkers (sST2, Galectin-3, GDF-15, and NT-proBNP) and postoperative outcome were assessed using logistic regressions and Cox proportional hazards models. The primary outcome was a composite of 30-day mortality, an inotropic support longer than 48 hours and an initial length of stay in the intensive carefive days. Secondary outcome measures were postoperative acute kidney injury, inotropic support duration, lengths of intensive care unit and hospital stays, and 30-day and one-year mortality. No association was observed between any of the four cardiac biomarkers and the primary outcome. The preoperative levels of Galectin-3 (hazard ratio = 1.2; p0.001) and sST2 (hazard ratio = 1.01, p0.001) were significantly associated with one-year survival, and their addition to the EuroSCORE II significantly improved the prediction of one-year mortality (p0.001). Similarly, Galectin-3 was associated with postoperative acute kidney injury (odds ratio = 1.15, p = 0.001) and improved the prediction of this complication when added to the EuroSCORE II (p = 0.002).These results suggested that the ability of cardiac biomarkers to predict short-term outcome after cardiac surgery, though of interest, appears limited. Conversely, cardiac biomarkers may have the potential to refine the prediction of long-term outcome. Admittedly, all positive results were obtained on secondary outcomes and must be regarded with caution.

Heart donation after circulatory death (DCD) can significantly expand the heart donor pool, helping to overcome the problem of organ shortage and the increase in waiting list mortality and morbidity. To improve the outcome of DCD heart transplantation, thoraco-abdominal normothermic regional perfusion (TA-NRP) can be performed by selectively restoring circulation followed by in vivo functional heart assessment. Here, we report on the use of periprocedural transoesophageal echocardiography (TOE) as a minimally invasive cardiac assessment tool during different stages of a DCD heart procurement procedure using TA-NRP. We conclude that TOE is a valuable method to assess the donor heart for transplantation eligibility before and after withdrawal of life-sustaining therapy and during subsequent TA-NRP.

Anemia is common before major abdominal surgery (35%). It is an independent factor for postoperative complications and longer length of stay (LOS). The aim of this study was to evaluate the extent to which preoperative anemia impacts on enhanced recovery programs (ERP) outcomes. The data for patients scheduled for colorectal surgery between 2015 and 2019, were analyzed (n = 494). All patients were managed with the same ERP. Demographic data, preoperative risk factors, postoperative complications, LOS and adherence to ERP were compared between anemic and non-anemic patients. Anemia was defined by a hemoglobin concentration

Streptococcus agalactiae (GBS) infective endocarditis (IE) is a rare clinical entity. It is associated with a high mortality rate compared to other streptococci endocarditis. The aim of this study ...

Background Staphylococcus capitis (S. capitis) is a subtype of coagulase-negative staphylococci and a commensal of the skin of the human scalp and forehead. S. capitis has been occasionally reported in infective endocarditis and rarely in prosthetic valve endocarditis (PVE). The purpose of this report is to present the clinical course and the surgical management of a series of four patients with S. capitis PVE. Methods The medical records of 190 adult patients with a definite diagnosis of infective endocarditis by the Duke modified criteria and who underwent surgery at our center between January 2008 and December 2018 were retrospectively reviewed. Results There were four cases of S. capitis infective endocarditis among 190 patients. All were male with an average age of 70.25 years (range, 58–80 years). The four cases were PVE: 3 aortic (1 mechanical and 2 biological bioprostheses) and 1 mitral (bioprosthesis). Their mean Euroscore II was 32.43 (range, 9.19–50.8). Three patients had underlying diseases (diabetes mellitus = 2, chronic obstructive pulmonary disease = 3, chronic kidney disease = 1, peripheral arterial disease = 2, ischemic heart disease = 1, dilated cardiomyopathy = 1). Preoperative clinical presentation was characterized by the occurrence of sepsis in three patients and heart failure and sepsis in one patient. Two patients presented with vegetation (mitral bioprosthesis, aortic bioprosthesis). A prosthetic dehiscence was present in all patients, and two presented with a localized annular abscess. All but one patient received triple antibiotic treatment with vancomycin plus rifampicin plus gentamycin. Surgery was performed on an urgent basis in all patients, and the in-hospital mortality rate was 50%. Conclusions While limited by the small number of patients, our series highlights the aggressive clinical course of S. capitis PVE with a mortality rate close to that of Staphylococcus aureus PVE. Therefore, early surgical management is recommended to improve the clinical outcome of this serious disease.

Enhanced recovery programme (ERP) reduces length of hospital stay (LOS) and postoperative complications after colorectal surgery. ERP is feasible and effective in elderly patients. We tested the hypothesis of non-inferiority for elderly patients as compared to younger patients with regard to LOS.The first 302 consecutive patients scheduled for colorectal surgery and prospectively introduced in our audit database were retrospectively analysed. LOS (primary endpoint), postoperative complications, and adherence to the ERP of elderly (≥70 years, n=100) were compared with those of younger patients (n=202). The same ERP was used in all patients. Non-inferiority hypothesis for LOS was tested using the confidence interval method. Secondary endpoints were compared using the Mann-Whitney U and the ChiExcept for age patients' demographic data were not different in both groups: 53.8 (17-69) vs. 76.8 (70-90) years. The actual LOS were 3.5 [2-7] and 4.0 [3-7] days in the young and elderly group, respectively. The difference in median LOS between the two groups was 0 (95% CI, -0.97-0.97), demonstrating non-inferiority. Although with more risk factors (anaemia, COPD, cardiac disease, and cancer, P0.05), elderly patients experienced neither more postoperative medical (17.0 vs. 16.3 %) nor surgical (19.0 vs. 22.3 %) complications than young patients. The adherence to protocol was slightly less in elderly (16 [15-18] vs. 17 [16-18], P=0.05).Not only ERP is feasible in seniors, but elderly patients benefit from this perioperative care as much as younger patients.NCT03620851.

BACKGROUND Heart transplantation (HT) from donation after circulatory death (DCD) has yet to achieve wide clinical application despite the encouraging resultsreported recently. In this study we describe 2 cases of successful adult DCD HT performed at our institution using an original protocol. METHODS Our local abdominal DCD protocol was updated to allow DCD heart procurement, and was accepted by the institutional ethics committee. The main features of the protocol include: pre-mortem insertion of peripheral venoarterial extracorporeal membrane oxygenation cannulas ; thoracoabdominal normothermic regional perfusion (NRP) by clamping the 3 aortic arch vessels to exclude cerebral circulation ; and in-situ heart resuscitation. The retrieved hearts were directly transplanted into recipients located in an adjoining operating room. RESULTS The procurement warm ischemic time was 25 minutes for the first donor, and 26 minutes for the second donor. The cold ischemic time was 16 minutes for the first recipient and 17 minutes for the second recipient. The suture time was 30 minutes for the first recipient, and 53 minutes for the second recipient. Both recipients were easily weaned off cardiopulmonary bypass in sinus rhythm and inotropic support. Post-operative evaluation of cardiac function was excellent and the patients were subsequently discharged home. CONCLUSIONS Transplantation of hearts from DCD donors is now a clinical reality.NRP is a useful tool for resuscitation, reperfusion, and preservation of transplanted hearts. It also offers the opportunity to assess the function and viability of organs before transplantation. However,due to ethical issues, some may object to ante-mortem intervention.

Objectives To investigate whether the Edmonton Frail Scale (EFS), a multidimensional frailty assessment tool, improves the prediction of 30-day or in-hospital mortality over the use of the European System for Cardiac Outcome Risk Evaluation (EuroSCORE) II alone. Design Single-center prospective observational study. Setting University hospital. Participants Patients aged 75 years or older undergoing cardiac surgery between February 2014 and May 2017. Intervention No intervention was performed. The EFS was administered the day before surgery. Measurements and Main Results The primary endpoint was 30-day or in-hospital mortality. Secondary endpoints were times to discharge from the intensive care unit (ICU) and from the hospital, discharge to a health care facility, and ability to return home by postoperative day 30. The EFS had a good discriminative ability for 30-day mortality (area under the receiver operating characteristic curve = 0.69; 95% confidence interval [CI], 0.56-0.82). Adding frailty, defined by an EFS ≥8, to the EuroSCORE II significantly improved the prediction of 30-day (p = 0.04) mortality. The integrated discrimination index was 0.03 (95% CI, 0.01-0.06, p = 0.01), meaning that the difference in predicted risk between patients who died and those who survived increased by 3% due to the addition of frailty determined by the EFS to the EuroSCORE II. Frailty also was associated significantly with a decreased cumulative probability of discharge from the ICU (p = 0.02) and an increased incidence of discharge to a health care facility (p = 0.01). Conclusion The EFS has a good predictive ability for 30-day mortality after cardiac surgery in elderly patients and improves the prediction of 30-day mortality over the use of the EuroSCORE II.

PLOS ONE 17(1), e0262110 (2022). doi:10.1371/journal.pone.0262110, Published by PLOS, San Francisco, California, US

BACKGROUND Preoperative use of antidepressants and anxiolytics was reported to increase length of hospital stay (LOS) and worsen surgical outcomes. However, the surgical procedures studied were seldom performed with an enhanced recovery programme (ERP). This study investigated whether these medications impaired postoperative recovery after colorectal surgery with an ERP. METHODS The data of all patients scheduled for colorectal surgery between November 2015 and December 2019 prospectively included in our database were analysed. All the patients were managed with the same ERP. Demographic data, risk factors, incidence of postoperative complications, LOS, and adherence to the ERP were compared between patients with and without preoperative antidepressant and/or anxiolytic treatment. RESULTS Of the 502 patients, 157 (31.3%) were treated with antidepressants and/or anxiolytics. They were older (65.7 vs. 59.5 years, p

BACKGROUND In patients scheduled for colorectal surgery with an enhanced recovery program (ERP), feeding after returning home has been insufficiently investigated. The aim of this study was to measure energy and protein intake during the first month at home. METHODS Seventy adult patients scheduled for colorectal surgery with ERP were included. Calorie and protein intakes were calculated, and body weight was measured preoperatively and 3, 7, 15, and 30 days after discharge home. Data are mean ± SD or median (interquartile range). RESULTS Patient characteristics were age 60.0 ± 15.0 years, BMI = 25.9 ± 5.5 kg/m2 , and colon/rectum of 56/14. The duration of hospitalization was 3 (2-5) days. Calorie and protein intakes (21.9 [17.7-28.6] kilocalorie per kilogram of ideal body weight [kcal/kg IBW] and 0.81 [0.61-1.14] g/kg IBW) were significantly reduced (P < .01) by 15% on day 3, compared with preoperative values, and then increased gradually to reach preoperative values after 1 month. Almost 50% of the patients failed to reach the calorie intake target of 25 kcal/kg IBW, and almost no patient reached the protein intake target of 1.5 g/kg IBW 30 days after discharge home. Weight loss after 30 days at home remained at -1.8 ± 2.7 kg. CONCLUSIONS Colorectal surgery, even in an ERP, is associated with energy and protein intake below the targets recommended for the rehabilitation phase and results in weight loss. Whether nutrition counseling and prolonged administration of protein-enriched oral supplements could accelerate weight gain needs to be explored.

Heart transplantation (HT) from donation after circulatory death (DCD) is a promising alternative to expand the heart donor pool. Cold storage can be used in a strategy to successfully retrieve and transplant DCD hearts after reconditioning using normothermic regional perfusion for distant procurement. Herein, we present the first report of a pediatric DCD heart reconditioned with normothermic regional perfusion, preserved using only cold storage while being transported to a neighboring center, and then successfully transplanted after nearly 2 hours of cold static storage. If supported by an appropriate trial, this finding could obviate the need to use expensive perfusion devices for short interhospital distances for DCD heart transportation and stimulate more centers across the world to embrace DCD HT. ispartof: JOURNAL OF HEART AND LUNG TRANSPLANTATION vol:38 issue:10 pages:1112-1115 ispartof: location:United States status: published

Objectives To investigate whether using hydroxyethyl starch (HES) 130/0.4 as a pump prime and for intraoperative fluid therapy is associated with postoperative acute kidney injury (AKI) after adult cardiac surgery. Design Retrospective observational study. Setting University hospital, single center. Participants Six hundred six adult patients who underwent on-pump cardiac surgery between April 2013 and June 2014 were included. Interventions Until July 2013, balanced HES 130/0.4 (Volulyte®, Fresenius Kabi AG, Bad Homburg, Germany) was used both as a pump prime (1,500 mL) and for intraoperative fluid therapy (1,000 mL). From August 2013, HES was replaced entirely by a balanced crystalloid solution (Plasma-Lyte A, Baxter, Lessines, Belgium). Measurements and Main Results The primary endpoint was the incidence of postoperative AKI during the first 48 postoperative hours, determined using the Acute Kidney Injury Network classification. Secondary outcomes included kidney function at postoperative day 7, postoperative dialysis or hemofiltration, postoperative pulmonary complications, lengths of intensive care unit and hospital stays, postoperative fluid balance and urinary output, surgical revision for bleeding, and 30-day mortality. Multivariable logistic regression was used to adjust for confounders. AKI occurred in 9.5% of crystalloid patients and in 21.5% of HES patients. Patients who received HES were about twice as likely to develop postoperative AKI as those treated with crystalloids (adjusted OR 2.26; 95% CI, 1.40-3.80; p = 0.02). HES patients also had a significantly more positive fluid balance and a lower urinary output during the first 48 postoperative hours. The incidence of surgical revision for bleeding was greater in the HES group (4.6% v 1.4%, p = 0.02). Conclusion This study suggested that using balanced HES 130/0.4 as a pump prime and for intraoperative fluid therapy in adult patients undergoing on-pump cardiac surgery was associated with a greater incidence of AKI during the early postoperative period.

To compare transfusion requirements in adult cardiac surgery patients when balanced hydroxyethyl starches (HES) (130/0.4) or balanced crystalloids is used for pump prime and intraoperative fluid therapy.Data were obtained retrospectively from medical records and perfusion charts. Matching based on propensity scores was used to adjust for potential confounders.A university hospital.Adult patients undergoing cardiac surgery with the use of cardiopulmonary bypass.Allocation to one of the study groups according to whether balanced HES or balanced crystalloids was used for pump prime and intraoperative fluid therapy.240 propensity-matched patients were retained for final analyses. Forty-eight patients (40%) of the colloid group and 28 patients (23.3%) of the crystalloid group received blood products, with an odd ratio (95% CI) of 2.1(1.2-3.8 (P=0.009). After bypass HES patients had lower hemoglobin levels (8.4 [1.3] gr/dL vs 9.6 [2] gr/dL; P0.001) and a higher cumulative chest drain output after 3 hours (180 [210] mL vs 140 [100] mL, P0.001]. Heparinase thromboelastogram (TEG®) showed longer K times (2.5[1.1] vs 1.6[0.8], P0.001) and lower maximal amplitudes (55.1[12.5] vs 63.4[9.8], P=0.008).HES patients required more transfusions, owing to greater hemodilution, HES-induced clotting disturbances, and bleeding.

BACKGROUND Enhanced recovery programme (ERP) has been used in our hospital since 2005 for selected colorectal surgeries. Since October 2015, after labelling as GRACE reference centre, we included all patients scheduled for elective colorectal surgery in this programme. We assessed the impact of our labelling on the implementation of ERP. METHODS Results of our first 100 patients entered in the GRACE database were analyzed: length of stay, complications, readmission, adherence to the protocol. These results are compared to those of the last 100 patients undergoing colorectal surgery before our labelling. RESULTS Patients' characteristics in both groups were similar. The complications rate was similar in both groups. The global length of hospital stay was 4 [5] days vs. 8.5 [8] (median [IQR]), respectively after and before labelling; p

Background Intraoperative recruitment manoeuvres (RMs) combined with PEEP reverse the decrease in functional residual capacity (FRC) associated with anaesthesia and improve intraoperative oxygenation. Whether these benefits persist after operation remains unknown. We tested the hypothesis that intraoperative RMs associated with PEEP improve postoperative spirometry including FRC and reduce the incidence of postoperative hypoxaemia in morbidly obese (MO) patients undergoing laparoscopic gastric bypass. Methods After IRB approval and informed consent, 50 MO patients undergoing laparoscopic gastric bypass under volume-controlled ventilation (tidal volume 6 ml kg −1 of IBW) were randomly ventilated with either 10 cm H 2 O PEEP or with 10 cm H 2 O PEEP and one RM carried out after induction of pneumoperitoneum, and another after exsufflation. Anaesthesia and analgesia were standardized. Spirometry was assessed before operation and 24 h after surgery. Postoperative oxygenation and the apnoea–hypopnoea index (AHI) were recorded during the first postoperative night. Results Age, BMI, and STOP BANG score were similar in both groups. FRC decrease after surgery was minimal [0.15 (0.14) litre in control and 0.38 (0.19) litre in the RM group] and similar between the groups ( P =0.35). FVC, FEV 1 , mean S p O 2 , percentage of time spent with S p O 2 below 90%, and AHI did not differ significantly between the groups. Conclusions This study demonstrates that when added to a protective mechanical ventilation combining low tidal volume and high PEEP, two RMs do not improve postoperative lung function including FRC, arterial oxygenation, and the incidence of obstructive apnoea in MO patients after laparoscopic upper abdominal surgery. Clinical trial registration EudraCT 2011-000999-33.

Introduction: Re-transfusion of lipid particles and activated leucocytes with shed mediastinal blood (SMB) can aggravate cardiopulmonary bypass-associated inflammation and increase the embolic load. This study evaluated the fat and leucocyte removal capacity of the RemoweLL cardiotomy reservoir. Methods: Forty-five patients undergoing elective on-pump cardiac surgery were randomly allocated to filtration of SMB using the RemoweLL or the Admiral cardiotomy reservoir. The primary outcome was a drop in leucocytes and lipid particles obtained with the two filters. The effect of the filters on other blood cells and inflammatory mediators, such as myeloperoxidase (MPO), was also assessed. Results: The RemoweLL cardiotomy filter removed 16.5% of the leucocytes (pConclusion: The RemoweLL filter more effectively removed leucocytes from SMB than the Admiral. It offered no advantage in terms of lipid particle clearance.

Background and Objectives Transversus abdominis plane block (TAP) and intravenous lignocaine are two analgesic techniques frequently used after abdominal surgery. We hypothesized that these two techniques improve post-operative analgesia after open prostate surgery and sought to compare their efficacy on immediate post-operative outcome after open prostate surgery. Methods After ethics committee approval, 101 patients were enrolled in this prospective study and randomly allocated to receive bilateral ultrasound-guided TAP (n = 34), intravenous lignocaine (n = 33) or placebo (n = 34). In addition, intravenous paracetamol was given every 6 h. The primary endpoint was the cumulative opioid consumption during the first 48 post-operative hours (median[IQR]). Secondary endpoints included pain scores at rest and upon coughing, need for rescue tramadol, incidence of post-operative nausea and vomiting (PONV), recovery of bowel function and incidence of bladder catheter-related discomfort. Results Cumulative piritramide consumption after 48 h was 28 [23] mg in the control group, 21 [29] mg in the TAP group and 21 [31] mg in the lignocaine group (P = 0.065). There was no significant difference in post-operative pain scores between groups. The proportions of patients requiring rescue tramadol, experiencing PONV or bladder catheter-related discomfort were similar in each group. Recovery of bowel function was also similar in the three groups. Conclusions Our study suggests that TAP block and intravenous lignocaine do not improve the post-operative analgesia provided by systematic administration of paracetamol after open prostatectomy.

Summary Anaesthesia produces muscle relaxation and consequently reduces lung volumes, especially the functional residual capacity. This leads to repeated closure of small airways and constitution of atelectases. Repeated closure of small airways and atelectases not only alter gas exchanges but also contribute to ventilator-induced lung injury. Over the last decade, accumulating experimental and clinical data encourage to revise ventilation of anaesthetized patients. Alveolar collapse can be prevented as soon as the induction of anaesthesia by positioning the patient in head-up position, applying a continuous positive airway pressure, and lowering the inspired oxygen fraction. During mechanical ventilation, positive end-expiratory pressure becomes the cornerstone of the prevention of alveolar de-recruitment. Despite these measures, atelectases do develop in some circumstances and need to be reversed by recruitment manoeuvres. In addition, the extent of the tidal volume should be decreased to limit pulmonary overdistension and subsequently ventilator-induced lung injury. The extubation phase is also critical since hypoventilation and re-occurrence of atelectases secondary to the administration of pure oxygen can occur during the transition between controlled and spontaneous ventilation. The efficient measures recommended during the induction of anaesthesia should be also applied during extubation. An assisted mode of ventilation could be beneficial to smoothen this transition phase.

Intravenous magnesium deepens non-depolarising neuromuscular block.To assess whether intravenous magnesium has the potential to re-establish paralysis in patients who have just recovered from a non-depolarising neuromuscular block.Prospective randomised double-blind controlled study.Twenty non-obese patients ranging in age from 18 to 80 years were enrolled. Exclusion criteria were a history of liver, kidney or neuromuscular disease and intake of medications interacting with neuromuscular blocking agents.After spontaneous recovery from an intubating dose of rocuronium had been achieved (train-of-four ratio ≥0.9), patients were given either a bolus dose of magnesium 50 mg kg(-1) intravenously or an equivalent volume of isotonic saline over 5 min.The train-of-four ratio was measured every minute until the end of surgery. The primary endpoint was the proportion of patients who experienced a decrease in train-of-four ratio following administration of magnesium or saline.Following infusion of the study solution, the train-of-four ratio decreased in all patients in the magnesium group in contrast to none in the saline group (P0.001). On average, magnesium-induced train-of-four ratio depression reached a nadir of 0.49 after 10 min and lasted for 45 min.A bolus dose of intravenous magnesium 50 mg kg(-1) re-establishes a clinically relevant degree of muscle paralysis in patients who have just recovered from a non-depolarising neuromuscular block.EudraCT.ema.europa.eu 2009-017372-24.

Background The Surgical Pleth Index (SPI), derived from pulse amplitude and heartbeat interval, is proposed to monitor anti-nociception during anaesthesia. Its response to noxious stimulation can be affected by the intravascular volume status. This study investigated the effect of a fluid challenge (FC) on SPI during steady-state conditions. Methods After Institutional Review Board approval, 33 consenting patients undergoing neurosurgery received a 4 ml/kg starch FC over less than 5 min under stable surgical stimulation conditions and stable propofol (CePPF) and remifentanil (CeREMI) effect-site concentrations as estimated by target-controlled infusion systems. Intravascular volume status was assessed using the Delta Down (DD). We looked at the SPI response to FC according to DD, CePPF, and CeREMI. Results Following FC, SPI did not change in 16, increased in 12, and decreased in 3 patients. CeREMI poorly affected the SPI response to FC. In normovolaemic patients, the probability of an SPI change after FC was low under common CePPF (0.9 to 3.9 μg/ml). A decrease in SPI was more probable with worsening hypovolaemia and lowering CePPF, while an increase in SPI was more probable with increasing CePPF. SPI changes were only attributable to modifications in pulse wave amplitude and not in heart rate. Conclusions During stable anaesthesia and surgery, SPI may change in response to FC. The effect of FC on SPI is influenced by volaemia and CePPF through pulse wave amplitude modifications. These situations may confound the interpretation of SPI as a surrogate measure of the nociception–anti-nociception balance.

Background The Surgical Pleth Index (SPI) is proposed as a means to assess the balance between noxious stimulation and the anti-nociceptive effects of anaesthesia. In this study, we compared SPI, mean arterial pressure (MAP), and heart rate (HR) as a means of assessing this balance. Methods We studied a standard stimulus [head-holder insertion (HHI)] and varying remifentanil concentrations (CeREMI) in a group of patients undergoing neurosurgery. Patients receiving target-controlled infusions were randomly assigned to one of the three CeREMI (2, 4, or 6 ng ml−1), whereas propofol target was fixed at 3 µg ml−1. Steady state for both targets was achieved before HHI. Intravascular volume status (IVS) was evaluated using respiratory variations in arterial pressure. Prediction probability (Pk) and ordinal regression were used to assess SPI, MAP, and HR performance at indicating CeREMI, and the influence of IVS and chronic treatment for high arterial pressure, as possible confounding factors. Results The maximum SPI, MAP, or HR observed after HHI correctly indicated CeREMI in one of the two patients [accurate prediction rate (APR)=0.5]. When IVS and chronic treatment for high arterial pressure were taken into account, the APR was 0.6 for each individual variable and 0.8 when all of them predicted the same CeREMI. That increase in APR paralleled an increase in Pk from 0.63 to 0.89. Conclusions SPI, HR, and MAP are of comparable value at gauging noxious stimulation–CeREMI balance. Their interpretation is improved by taking account of IVS, treatment for chronic high arterial pressure, and concordance between their predictions.

Background. I.V. lidocaine reduces volatile anaesthetics requirements during surgery. We hypothesized that lidocaine would also reduce propofol requirements during i.v. anaesthesia. Methods. A randomized controlled study of 40 patients tested the effect of i.v. lidocaine (1.5 mg kg 21 then 2 mg kg 21 h 21 ) on propofol requirements. Anaesthesia was maintained with remifentanil and propofol target-controlled infusions (TCI) to keep the bispectral index (BIS) around 50. Effect-site concentrations of propofol and remifentanil and BIS values were recorded before and after skin incision. Data were analysed using ANOVA and mixed effects analysis with NONMEM. Two dose –response studies were then performed with and without surgical stimulation. Propofol TCI titrated to obtain a BIS around 50 was kept constant. Then patients were randomized into four groups: A, saline; B, 0.75 mg kg 21 bolus then infusion 1 mg kg 21 h 21 ; C, 1.5 mg kg 21 bolus and infusion 2 mg kg 21 h 21 ; and D, 3 mg kg 21 bolus and infusion 4 mg kg 21 h 21 . Lidocaine administration coincided with skin incision. BIS values and haemodynamic variables were recorded. Data were analysed using linear regression and two-way ANOVA. Results. Lidocaine decreased propofol requirements (P,0.05) only during surgery. In the absence of surgical stimulation, lidocaine did not affect BIS nor haemodynamic variables, whereas it reduced BIS increase (P¼0.036) and haemodynamic response (P¼0.006) secondary to surgery. Conclusions. The sparing effect of lidocaine on anaesthetic requirements seems to be mediated by an anti-nociceptive action.

University Departmentof Anaesthesia and Intensive Care Medicine, CHR de la Citadelle, Lie`ge, BelgiumBackground: Intravenous lidocaine can be used intrao-peratively for its analgesic and antihyperalgesic pro-perties but local anaesthetics may also prolong theduration of action of neuromuscular blocking agents. Wehypothesized that intravenous lidocaine would prolongthetimetorecoveryofneuromuscularfunctionaftercisatracurium.Methods: Forty-two patients were enrolled in this rando-mized, double-blind, placebo-controlled study. Before in-duction, patients were administered either a 1.5mg/kgbolus of intravenous lidocaine followed by a 2mg/kg/hinfusion or an equal volume of saline. Anaesthesia wasinduced and maintained using propofol and remifentanilinfusions. After loss of consciousness, a 0.15mg/kg bolusof cisatracurium was administered. No additional cisatra-curium injection was allowed. Neuromuscular functionwas assessed every 20s using kinemyography. The pri-mary endpoint was the time to spontaneous recovery of atrain-of-four (TOF) ratio 0.9.Results: ThetimetospontaneousrecoveryofaTOFratio 0.9 was 94 15min in the control group and98 16min in the lidocaine group (P50.27).Conclusions: No significant prolongation of spontaneousrecovery of a TOF ratio 0.9 after cisatracurium wasfound in patients receiving intravenous lidocaine.

Hellmut Hartert was the first person to exploit the viscoelastic properties of clotting blood to measure blood coagulation in 1948. Since then, the technology has improved, allowing these analyses to be performed as point-of-care tests with immediately-available results. The addition of several activators and inhibitors to the original assay creates a panel of tests able to quantify the different aspects of blood clotting that can rival conventional laboratory assays. However, although much progress has been made, the standardization and validation of these tests still need improvement. Viscoelastic analyses of blood coagulation are mainly used to guide haemostatic therapy in bleeding patients and have proven superior to standard clotting tests in some circumstances. There is potential to extend their use to other areas, such as drug monitoring, and diagnosis and management of congenital bleeding disorders. The forthcoming cartridge-based assays are expected to improve the reliability and usability of viscoelastic assays of blood coagulation but high quality clinical trials remain urgently needed to determine their exact place, benefit and cost effectiveness.

Objectives: Predicting the post-dilution hematocrit is an important tool to avoid preventable anemia or unnecessary transfusion. Simplified empirical formulas currently used for such a prediction may lead to large errors. We aimed to improve the accuracy of these formulas by a better estimation of the dilution volume and the patient circulatory blood volume. Methods: We compared the estimation accuracy of two formulas, using fixed (formula A) versus estimated (formula D) dilution volume and patient circulatory blood volume for 100 cardiac interventions. The difference between predicted and measured HctT1 was considered as “good” if less than 0.5%, “moderate” between 0.5 and 2% and “poor” if higher than 2%. The influence of the body mass index (BMI) on patient blood volume estimation was explored by categorized groups’ comparison. Results: The mean difference between predicted and measured HctT1 differed significantly between formulas A and D. Formula A didn’t differ from HctT1 (p=0.19, IC95% [-0.89-0.18]), but a significant and higher underestimation was observed in the BMI⩽25 group compared to the other BMI groups (pConclusions: Formulas used for post-dilution hematocrit prediction lead to major estimation errors and a risk of inadequate transfusion practices. Estimations performed by experienced clinicians could not minimize these biases in all clinical cases as significant errors remain, with potential clinical impact. No estimation formula should be used as a hard tool for transfusing patients, but rather as a guide to predicting the probability of transfusion requirement.

Precise assessment of left ventricular (LV) contractility during veno-arterial extracorporeal membrane oxygenation (VA-ECMO) is crucial. However, changes in loading conditions may mask changes in LV function when assessed with load-dependent indices like LV ejection fraction (LVEF). Indeed, these indices do not reflect intrinsic LV contractility but are the result of interaction between preload, contractile function and afterload [1].

Some synthetic ligands of the peripheral-type benzodiazepine receptor (PBR), an 18 kDa protein of the outer mitochondrial membrane, are cytotoxic for several tumor cell lines and arise as promising chemotherapeutic candidates. However, conflicting results were reported regarding the actual effect of these drugs on cellular survival ranging from protection to toxicity. Moreover, the concentrations needed to observe such a toxicity were usually high, far above the affinity range for their receptor, hence questioning its specificity. In the present study, we have shown that micromolar concentrations of FGIN-1-27 and Ro 5-4864, two chemically unrelated PBR ligands are toxic for both PBR-expressing SK-N-BE neuroblastoma cells and PBR-deficient Jurkat lymphoma cells. We have thereby demonstrated that the cytotoxicity of these drugs is unrelated to their PBR-binding activity. Moreover, Ro 5-4864-induced cell death differed strikingly between both cell types, being apoptotic in Jurkat cells while necrotic in SK-N-BE cells. Again, this did not seem to be related to PBR expression since Ro 5-4864-induced death of PBR-transfected Jurkat cells remained apoptotic. Taken together, our results show that PBR is unlikely to mediate all the effects of these PBR ligands. They however confirm that some of these ligands are very effective cytotoxic drugs towards various cancer cells, even for reputed chemoresistant tumors such as neuroblastoma, and, surprisingly, also for PBR-lacking tumor cells.

In the current study, we have investigated the ability of substance P (SP) to protect 3-day-old (P3) rat spiral ganglion neurons (SGNs) from trophic factor deprivation (TFD)-induced cell death. The presence of SP high affinity neurokinin-1 receptor (NK1) transcripts was detected in the spiral ganglion and the NK1 protein localized to SGNs both ex vivo and in vitro. Treatment with SP increased cytoplasmic Ca2+ in SGNs, further arguing for the presence of functional NK1 on these neurons. Both SP and the agonist [Sar9,Met(O2)11]-SP significantly decreased SGN cell death induced by TFD, with no effect on neurite outgrowth. The survival promoting effect of SP was blocked by the NK1 antagonist, WIN51708. Both pan-caspase inhibitor BOC-D-FMK and SP treatments markedly reduced activation of caspases and DNA fragmentation in trophic factor deprived-neurons. The neuroprotective action of SP was antagonised by specific inhibitors of second messengers, including 1.2-bis-(O-aminophenoxy)-ethane-N,N,N′,N′-tetraacetic acid (BAPTA-AM) to chelate cytosolic Ca2+, the protein kinase C (PKC) inhibitors bisindolylmaleimide I, Go6976 and LY333531 and the MAPK/ERK inhibitor U0126. In contrast, nifedipine, a specific inhibitor of l-type Ca2+ channel, and LY294002, a phosphatidylinositol-3-OH kinase (PI3K) inhibitor, had no effect on SP trophic support of SGNs. Moreover, activation of endogenous PKC by 4β-phorbol 12-myristate 13-acetate (PMA) also reduced the loss of trophic factor-deprived SGNs. Thus, NK1 expressed by SGNs transmit a survival-promoting regulatory signal during TFD-induced SGN cell death via pathways involving PKC activation, Ca2+ signalling and MAPK/ERK activation, which can be accounted for by an inhibition of caspase activation.

1. In this study in vitro and in vivo approaches were combined in order to investigate if the anti-epileptic mechanism(s) of action of levetiracetam (LEV; Keppra) may involve modulation of inhibitory neurotransmission. 2. GABA- and glycine-gated currents were studied in vitro using whole-cell patch-clamp techniques applied on cultured cerebellar granule, hippocampal and spinal neurons. Protection against clonic convulsions was assessed in vivo in sound-susceptible mice. The effect of LEV was compared with reference anti-epileptic drugs (AEDs): carbamazepine, phenytoin, valproate, clonazepam, phenobarbital and ethosuximide. 3. LEV contrasted the reference AEDs by an absence of any direct effect on glycine-gated currents. At high concentrations, beyond therapeutic relevance, it induced a small reduction in the peak amplitude and a prolongation of the decay phase of GABA-gated currents. A similar action on GABA-elicited currents was observed with the reference AEDs, except ethosuximide. 4. These minor direct effects contrasted with a potent ability of LEV (EC(50)=1 - 10 microM) to reverse the inhibitory effects of the negative allosteric modulators zinc and beta-carbolines on both GABA(A) and glycine receptor-mediated responses. 5. Clonazepam, phenobarbital and valproate showed a similar ability to reverse the inhibition of beta-carbolines on GABA-gated currents. Blockade of zinc inhibition of GABA responses was observed with clonazepam and ethosuximide. Phenytoin was the only AED together with LEV that inhibited the antagonism of zinc on glycine-gated currents and only clonazepam and phenobarbital inhibited the action of DMCM. 6. LEV (17 mg kg(-1)) produced a potent suppression of sound-induced clonic convulsions in mice. This protective effect was significantly abolished by co-administration of the beta-carboline FG 7142, from a dose of 5 mg kg(-1). In contrast, the benzodiazepine receptor antagonist flumazenil (up to 10 mg kg(-1)) was without any effect on the protection afforded by LEV. 7. The results of the present study suggest that a novel ability to oppose the action of negative modulators on the two main inhibitory ionotropic receptors may be of relevance for the anti-epileptic mechanism(s) of action of LEV.

Hydroxyethyl starches (HES) affect the results of thromboelastography (TEG®). We sought to determine whether using HES rather than crystalloids for cardiopulmonary bypass (CPB) prime and intraoperative fluid therapy changes the TEG cutoff values best identifying patients with a low platelet count or a low fibrinogen level after CPB.Data from 96 patients who had on-pump cardiac surgery, a TEG® (kaolin-heparinase) and standard investigations of blood clotting performed after separation from CPB and protamine administration were retrospectively reviewed. Patients were assigned to the HES or crystalloid group according to whether balanced 6% HES 130/0.4 or balanced crystalloids were used for intraoperative fluid therapy and pump prime. Mutlivariable linear regression models with computation of the standardized regression coefficients were used to identify independent associations between the four main TEG parameters (R time, alpha angle, K time and MA) and the type of fluid used, the INR, the aPTT, the fibrinogen level and the platelet count. Receiver-operating-characteristic curves were used to assess the effect of HES on the ability of TEG parameters to identify patients with a platelet count80.000μl(-1) or a fibrinogen level1.5 gr l(-1) and on the cutoff values best identifying these patients.The type of fluid used significantly affected the MA (P0.001), the K time (P0.001) and the alpha angle (P0.001) regardless of the results of the standard clotting tests. According to standardized ß regression coefficients the platelet count and the type of fluid used were stronger predictors of the MA, the alpha angle and the K time than the fibrinogen level. MA better predicted platelets80.000μl(-1) than K time and alpha angle (P=0.023). The best cutoff value of MA identifying patients with platelets80.000μl(-1) was 62mm in the crystalloid group and 53mm in the HES group. MA, K time and alpha angle were poor predictors of the postoperative fibrinogen level.HES significantly changes the cutoff value of TEG® MA best identifying patients80.000μl(-1) after on-pump cardiac surgery.

Using fluo-3 calcium imaging, we demonstrate that glycine induces an increase in intracellular calcium concentration ([Ca2+]i) in cortical oligodendrocyte progenitor (OP) cells. This effect results from a calcium entry through voltage-gated calcium channels (VGCC), as it is observed only in OP cells expressing such channels, and it is abolished either by removal of calcium from the extracellular medium or by application of an l-type VGCC blocker. Glycine-triggered Ca2+ influx in OP cells actually results from an initial depolarization that is the consequence of the activation of both the ionotropic glycine receptor (GlyR) and Na+-dependent transporters, most probably the glycine transporters 1 (GLYT1) and/or 2 (GLYT2) which are colocalized in these cells. Through this GlyR- and transporter-mediated effect on OP intrcellular calcium concentration [Ca2+]i, glycine released by neurons may, as well as other neurotransmitters, serve as a signal between neurons and OP during development.

Since its introduction in the 1980s, the advantages of the laryngeal mask airway (LMA) were quickly recognized and LMAs progressively replaced tracheal intubation in many cases. Because positive pressure ventilation results in higher airway pressures in obese patients and because these patients were previously believed to be at increased risk of regurgitation, obesity has been considered as a contra-indication to the use of an LMA. The risk of pulmonary aspiration during general anesthesia in obese patients has been reconsidered. Furthermore, during the past decade, several new supraglottic airway (SGA) devices with high leak pressures have been introduced into clinical practice. These newer SGAs are potentially more suitable for use in obese patients. In this chapter, we review the potential role of SGA devices in the management of obese patients and propose a practical guide to help deciding whether or not the trachea of an obese patient requiring mechanical ventilation should be intubated.

Paracetamol (acetaminophen) is widely used for postoperative analgesia at a recommended dose of 1 g every six hours in adult patients. Increasing the loading dose to 2 g was suggested to improve immediate postoperative analgesia without increased toxicity in healthy adult patients. We tested the hypothesis that a loading dose of 2 g of intravenous paracetamol results in better postoperative analgesia after surgery as compared with a dose of 1 g.Sixty adult patients scheduled for minor hand surgery under intravenous regional anaesthesia were randomized into two groups. The first group received 1 g of intravenous paracetamol before surgery while the second group received 2 g. Verbal numeric pain score, analgesic consumption, first night sleep quality, and patient's satisfaction were recorded during the first 24 hours.Verbal numeric pain scores during the first 24 hours after surgery were significantly lower in the 2 g paracetamol group as compared to the 1 g paracetamol group. No differences were found between the two groups with regard to rescue analgesic consumption, sleep quality and patient's satisfaction.An intraoperative loading dose of 2 g paracetamol improves postoperative analgesia after minor hand surgery as compared to 1 g paracetamol.

Intraoperative hypoxaemia and postoperative respiratory complications remain the challenges of modern anaesthetic practice. Anaesthesia causes both depression of respiratory centres and profound changes of respiratory mechanics. Most anaesthetized patients consequently require mechanical ventilation and supplemental oxygen. Recent data suggest that intraoperative respiratory management of a patient can affect postoperative outcome. In this review, we briefly describe the mechanisms responsible for the impairment of intraoperative gas exchange and provide guidelines to prevent or manage hypoxaemia. Moreover, we discuss several aspects of mechanical ventilation that can be employed to improve patients' outcome.

Morbid obesity results in marked respiratory pathophysiologic changes that may lead to impaired intraoperative gas exchange. The decelerating inspiratory flow and constant inspiratory airway pressure resulting from pressure-controlled ventilation (PCV) may be more adapted to these changes and improve gas exchanges compared with volume-controlled ventilation (VCV).Forty morbidly obese patients scheduled for gastric bypass were included in this study. Total intravenous anesthesia was given using the target-controlled infusion technique. During the first intraoperative hour, VCV was used and the tidal volume was adjusted to keep end-tidal PCO(2) around 35 mmHg. After 1 h, patients were randomly allocated to 30-min VCV followed by 30-min PCV or the opposite sequence using a Siemens Servo 300. FiO(2) was 0.6. During PCV, airway pressure was adjusted to provide the same tidal volume as during VCV. Arterial blood was sampled for gas analysis every 15 min. Ventilatory parameters were also recorded.Peak inspiratory airway pressures were significantly lower during PCV than during VCV (P0.0001). The other ventilatory parameters were similar during the two periods of ventilation. PaO(2) and PaCO(2) were not significantly different during PCV and VCV.PCV does not improve gas exchange in morbidly obese patients undergoing gastric bypass compared to VCV.

In mammals, degeneration of peripheral auditory neurons constitutes one of the main causes of sensorineural hearing loss. Unfortunately, to date, pharmacological interventions aimed at counteracting this condition have not presented complete effectiveness in protecting the integrity of cochlear neural elements. In this context, the protein kinase C (PKC) family of enzymes are important signalling molecules that play a role in preventing neurodegeneration after nervous system injury. The present study demonstrates, for the first time, that the PKC signalling pathway is directly neurotrophic to axotomised spiral ganglion neurons (SGNs). We found that PKCβI was strictly expressed by postnatal and adult SGNs both in situ and in vitro. In cultures of SGNs, we observed that activators of PKC, such as phorbol esters and bryostatin 1, induced neuronal survival and neurite regrowth in a manner dependent on the activation of PKCβI. The neuroprotective effects of PKC activators were suppressed by pre-treatment with LY294002 (a PI3K inhibitor) and with U0126 (a MEK inhibitor), indicating that PKC activators promote the survival and neurite outgrowth of SGNs by both PI3K/Akt and MEK/ERK-dependent mechanisms. In addition, whereas combining the neurotrophins brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT3) was shown to provide only an additive effect on SGN survival, the interaction between PKC and neurotrophin signalling gave rise to a synergistic increase in SGN survival. Taken together, the data indicate that PKCβI activation represents a key factor for the protection of the integrity of neural elements in the cochlea.

Most hearing loss results from lesions of the sensory cells and/or neurons of the auditory portion of the inner ear. To date, only the cochlear implantation offers long-term hearing-aid benefit, but still with limited performance and expensive cost. While the underlying causes of deafness are not clear, the death or hair cells and/or neurons and the loss of neuronal contacts are key pathological features. Pinpointing molecular events that control cell death in the cochlea is critical for the development of new strategies to prevent and treat deafness, whether in combination or not with cochlear implant therapy.

In this work, we show that beta-carbolines, which are known negative allosteric modulators of GABA(A) receptors, inhibit glycine-induced currents of embryonic mouse spinal cord and hippocampal neurons. In both cell types, beta-carboline-induced inhibition of glycine receptor (GlyR)-mediated responses decreases with time in culture. Single-channel recordings show that the major conductance levels of GlyR unitary currents shifts from high levels (> or = 50 pS) in 2 to 3 days in vitro (DIV) neurons to low levels ( or = 50 pS) in GlyR-alpha2-transfected cells to low levels (

N-Butyl-beta-carboline-3-carboxylate (betaCCB) is, together with 2-methyl-norharmanium and 2,9-dimethylnorharmanium ions, an endogenously occurring beta-carboline. Due to their structural similarities with the synthetic neurotoxin 1-methy14-phenyl-1,2,3,6-tetrahydropyridine (MPTP), harman and norharman compounds have been proposed to be involved in the pathogenesis of Parkinson's disease. While also structurally related, betaCCB has received much less interest in that respect although we had previously demonstrated that it induces the apoptotic cell death of cultured cerebellar granule neurons (CGNs). Herein, we have investigated the molecular events leading to CGN apoptosis upon betaCCB treatment. We first demonstrated that betaCCB-induced apoptosis occurs in neurons only, most likely as a consequence of a specific neuronal uptake as shown using binding/uptake experiments. Then we observed that, in betaCCB-treated CGNs, caspases 9, 3 and 8 were successively activated, suegesing an activation of the mitochondrial pathway. Consistently, betaCCB also induced the release from the mitochondrial intermembrane space of two pro-apoptotic factors. i.e. cytochrome c and apotptosis inducing factor (AIF). Interestingly, no mitochondrial membrane depolarisation was associated with this release. suggesting a mitochondrial permeability transition pore-independent mechanism. The absence of any neuroprotective effect provided by two mPTP inhibitors. i.e. cyclosporine A and bongkrekic acid. further supported this hypothesis. Together. these results show that betaCCB is specifically taken up by neuronal cells where it triggers a specific permeabilization of the outer mitochondrial membrane and a subsequent apoptotic cell death. (C) 2004 Elsevier Ltd. All rights reserved.

Immunocytochemical analysis showed that ionotropic glycine receptors are expressed in neurogenic progenitors purified from the newborn rat striatum and expressing the polysialylated form of the neural cell adhesion molecule, both in vitro and in situ. To ascertain whether glycine receptors were functional in vitro, whole-cell patch-clamp recordings demonstrated that glycine triggers inward strychnine-sensitive currents in the majority of these cells. Moreover, we found that glycine receptors expressed by these neurogenic progenitors display intermediate electrophysiological characteristics between those of glycine receptors expressed by neural stem cells and by mature interneurons from the rat striatum. Altogether, the present data show that functional strychnine-sensitive glycine receptors are expressed in neurogenic progenitors purified from the newborn rat striatum.