Is Brain-Dead Donor Fluid Therapy With Colloids Associated With Better Kidney Grafts?

Objectives: Fluid therapy is required to maintain perfusion to donor organs. Recent reviews on the choices of fluids have emphasized the safety of using crystalloids, as opposed to fluid therapy with colloids, which has been reported to be either unequivocally or potentially harmful in a number of studies on various patient populations. We aimed to analyze whether the type of fluid administered to donors is connected with kidney transplant outcomes. Materials and Methods: A total of 100 consecutive brain-dead multiorgan donors and their respective 181 kidney recipients were studied retrospectively. Data concerning donor fluid therapy, the characteristics of the donors and the recipients, and outcomes after kidney transplant were extracted from organ retrieval and patient records. Cases with early graft function were compared with cases with delayed graft function. Results: Donors had received both crystalloids and colloids in most cases (84%). Fluid therapy with crystalloids alone was more common among the 40 recipients with delayed (30%) than in the 103 recipients with early graft function (11%) (P = .005). Donor age, time on renal replacement therapy before transplant, and donor fluid therapy with crystalloids alone were independent risk factors for delayed graft function in multivariate analysis. Conclusions: Our results suggest that donor fluid therapy including colloids could be beneficial instead of harmful compared with treatment with crystalloids alone. This finding needs to be evaluated in prospective studies.Peer reviewe

Transfusion Threshold of Hemoglobin 80 g/L Is Comparable to 100 g/L in Terms of Bleeding in Cardiac Surgery : A Prospective Randomized Study

Objective: Anemia is common after cardiac surgery and, according to some suggestive evidence, may be associated with increased bleeding, other morbidity, and mortality. However, transfusion of red blood cells (RBC) may cause adverse effects and increase cost. The authors hypothesized that the restrictive hemoglobin threshold (Hb of 80 g/L) may aggravate bleeding more than the higher Hb threshold (Hb 100 g/L). Design: Prospective randomized trial. Type of Hospital: University Hospital of Helsinki, Finland. Participants: Eighty patients with written informed consent, scheduled for elective open-heart surgery were randomized in 2 groups. Interventions: Two study groups had RBC transfusion threshold of either Hb 80 g/L or 100 g/L. These triggers were followed for a 24-hour period postoperatively. A medical follow-up was carried out for 7 days after surgery. Measurements and Main Results: Rotational thromboelastometry (ROTEM) and conventional laboratory tests were performed to evaluate coagulation. There was no significant difference in bleeding or ROTEM parameters between the groups. Complication rate and Hb concentration after 7-day follow-up were not different between the groups, but Group 100 g/L had received twice the amount of RBC transfusions. Conclusion: Hb threshold of 80 g/L for RBC transfusion in cardiac surgery is comparable to 100 g/L in terms of bleeding and possibly short-term complications. (C) 2018 Elsevier Inc. All rights reserved.Peer reviewe

Postoperative Volume Therapy in Cardiac Surgery : Effects on Hemostatic and Circulatory Variables

Background: Patients may need massive volume-replacement therapy after cardiac surgery because of large fluid transfer perioperatively, and the use of cardiopulmonary bypass. Hemodynamic stability is better maintained with colloids than crystalloids but colloids have more adverse effects such as coagulation disturbances and impairment of renal function than do crystalloids. The present study examined the effects of modern hydroxyethyl starch (HES) and gelatin solutions on blood coagulation and hemodynamics. The mechanism by which colloids disturb blood coagulation was investigated by thromboelastometry (TEM) after cardiac surgery and in vitro by use of experimental hemodilution. Materials and methods: Ninety patients scheduled for elective primary cardiac surgery (Studies I, II, IV, V), and twelve healthy volunteers (Study III) were included in this study. After admission to the cardiac surgical intensive care unit (ICU), patients were randomized to receive different doses of HES 130/0.4, HES 200/0.5, or 4% albumin solutions. Ringer’s acetate or albumin solutions served as controls. Coagulation was assessed by TEM, and hemodynamic measurements were based on thermodilutionally measured cardiac index (CI). Results: HES and gelatin solutions impaired whole blood coagulation similarly as measured by TEM even at a small dose of 7 mL/kg. These solutions reduced clot strength and prolonged clot formation time. These effects were more pronounced with increasing doses of colloids. Neither albumin nor Ringer’s acetate solution disturbed blood coagulation significantly. Coagulation disturbances after infusion of HES or gelatin solutions were clinically slight, and postoperative blood loss was comparable with that of Ringer’s acetate or albumin solutions. Both single and multiple doses of all the colloids increased CI postoperatively, and this effect was dose-dependent. Ringer’s acetate had no effect on CI. At a small dose (7 mL/kg), the effect of gelatin on CI was comparable with that of Ringer’s acetate and significantly less than that of HES 130/0.4 (Study V). However, when the dose was increased to 14 and 21 mL/kg, the hemodynamic effect of gelatin rose and became comparable with that of HES 130/0.4. Conclusions: After cardiac surgery, HES and gelatin solutions impaired clot strength in a dose-dependent manner. The potential mechanisms were interaction with fibrinogen and fibrin formation, resulting in decreased clot strength, and hemodilution. Although the use of HES and gelatin inhibited coagulation, postoperative bleeding on the first postoperative morning in all the study groups was similar. A single dose of HES solutions improved CI postoperatively more than did gelatin, albumin, or Ringer’s acetate. However, when administered in a repeated fashion, (cumulative dose of 14 mL/kg or more), no differences were evident between HES 130/0.4 and gelatin.Tausta: Kolloidiliuokset (hydroksietyylitärkkelysliuos (HES), gelatiini, albumiini) ovat tehokkaita kirurgisten potilaiden neste-elvytyksessä sekä verenvuodon korvaushoidossa. Ne saattavat vaikuttaa veren hyytymisjärjestelmään ja siten lisätä leikkaukseen liittyvän vuodon riskiä. Sydänkirurgiassa kehon ulkopuolinen verenkierto heikentää hyytymisjärjestelmän toimintaa. Sydänleikkauksen jälkeen potilaat tarvitsevat riittävän veritilavuuden ylläpitämiseksi usein runsaasta nesteytystä, ja samanaikaisesti ovat vuotovaarassa. Tämän vuoksi liuosten vaikutus hyytymisjärjestelmään ja sydämen toimintaan on sydänleikkauspotilailla tärkeä. Tutkimuksen tavoitteena oli selvittää, kuinka voimakkaasti erilaiset täyttöliuokset vaikuttavat veren hyytymiseen ja sydämen toimintaan sydänleikkauspotilailla käyttäen uusia HES- ja gelatiiniliuoksia. Hyytymishäiriön mekanismit tutkittiin tromboelastometrialla (TEM) sydänkirurgian jälkeen, sekä lisäksi koehenkilöillä. Menetelmät: 90 potilasta ja 12 tervettä koehenkilöä osallistuivat tutkimukseen. Potilailla oli hyvä sydämen pumppausfunktio, eikä heillä ollut maksan- tai munuaisten vajaatoimintaa. Teho-osastolle tulleessa potilaat randomoitiin saamaan eri annoksia HES 130/0.4-, HES 200/0.5-, tai gelatiiniliuosta. Kontrollina oli joko 4% albumiini tai Ringerin liuokset. Hyytymistä seurattiin TEM:a käyttäen, hemodynaamiset mittaukset tehtiin keuhkovaltimokatetrin avulla. Tulokset: HES- sekä gelatiiniliuokset aiheuttivat samanlaisen hyytymishäiriön jo pienillä annoksilla. Nämä liuokset heikensivät hyytymän lujuutta ja pidensivät hyytymisaikaa annosriippuvaisesti. Albumiini eikä Ringerin liuos vaikuttanut hyytymiseen. Hyytymishäiriö käyttäen HES- ja gelatiiniliuoksia oli kliinisesti vähäinen. Leikkauksen jälkeinen verenvuoto oli samanlainen kuin Ringerin tai albumiinin käytön jälkeen. Sekä kerta- että toistuvat annokset kolloideja nostivat sydämen minuuttivirtauksen, ja tämä vaikutus oli annosriippuvainen. Ringerin liuos ei vaikuttanut sydämen minuuttivirtaukseen. Ensimmäisenä postoperatiivisena aamuna sydämen minuuttivirtaus oli samanlainen kaikissa ryhmissä. HES:n vaikutus hemodynamiikkaan oli samanlainen, mutta albumiinia parempi. Pienellä annoksella (7 mL/kg) gelatiinin vaikutus sydämen minuuttivirtaukseen oli tilastollisesti matalampi kuin HES 130/0.4 liuoksella, ja verrattavissa Ringeriin. Annosta nostaessa (14 ja 21 mL/kg), gelatiinin vaikutus kuitenkin nousi ja oli samanlainen kuin HES 130/0.4 liuoksella. Yhteenveto: Sydänkirurgian jälkeen, HES ja gelatiini liuokset heikentävät hyytymän lujuutta annosriippuvaisesti. Mahdolliset hyytymishäiriön mekanismit ovat vaikutus fibriinin muodostumiseen, fibrinogeeniin sekä hemodiluutio. Vaikka HES 130/0.4-, HES 200/0.5- ja gelatiiniliuokset aiheuttavat hyytymishäiriön, leikkauksen jälkeinen verenvuoto on verrattavissa albumiiniin ja Ringeriin. HES liuosten kerta-annos nostaa sydämen minuuttivirtausta enemmän kuin gelatiini, albumiini tai Ringerin liuos. Toistuvia annoksia käyttäen, HES 130/0.4 ja gelatiinin vaikutus oli samanlainen. HES 130/0.4 ominaisuus parantaa hemodynamiikkaa yksittäisellä pienellä annoksella on erittäin tärkeä sydänkirurgisilla potilailla massivisten nesteensiirtojen yhteydessä

Hyvän tieteellisen ohjaustyön eväät

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Effect of Albumin in Combination With Mannitol on Whole-blood Coagulation In Vitro Assessed by Thromboelastometry

Background:Albumin and mannitol may interfere with hemostasis, but their coinfluence is unclear. We aimed to determine the effects of albumin alone and in combination with mannitol or Ringer acetate (RAC) on hemostasis in crossover in vitro study.Materials and Methods:From citrated fresh whole blood withdrawn from 10 volunteers, we prepared 2.5, 5, 10, 15, and 20 vol% dilutions of 4% albumin (Alb group). Each sample was thereafter diluted by 15% mannitol (Alb/Man group) or RAC (Alb/RAC group) at a ratio of 9:1. Using thromboelastometry, FibTEM (fibrinogen ROTEM) and ExTEM (extrinsic ROTEM) tests were performed.Results:A 20 vol%, but not 2.5 to 15 vol% dilution of albumin caused a prolonged clot formation time, -angle decrease, and maximum clot firmness (MCF) weakening compared with undiluted sample (PPeer reviewe

Point-of-care laboratory analyses of intraosseous, arterial and central venous samples during experimental cardiopulmonary resuscitation

Introduction: Screening and correcting reversible causes of cardiac arrest (CA) are an essential part of cardiopulmonary resuscitation (CPR). Point-ofcare (POC) laboratory analyses are used for screening pre-arrest pathologies, such as electrolyte disorders and acid-base balance disturbances. The aims of this study were to compare the intraosseous (10), arterial and central venous POC values during CA and CPR and to see how the CPR values reflect the pre-arrest state. Methods: We performed an experimental study on 23 anaesthetised pigs. After induction of ventricular fibrillation (VF), we obtained POC samples from the 10 space, artery and central vein simultaneously at three consecutive time points. We observed the development of the values during CA and CPR and compared the CPR values to the pre-arrest values. Results: The 10, arterial and venous values changed differently from one another during the course of CA and CPR. Base excess and pH decreased in the venous and 10 samples during untreated VF, but in the arterial samples, this only occurred after the onset of CPR. The 10, arterial and venous potassium values were higher during CPR compared to the pre-arrest arterial values (mean elevations 4.4 mmol/l (SD 0.72), 3.3 mmol/l (0.78) and 2.8 mmol/l (0.94), respectively). Conclusions: A dynamic change occurs in the common laboratory values during CA and CPR. POC analyses of lactate, pH, sodium and calcium within 10 samples are not different from analyses of arterial or venous blood. Potassium values in 10, arterial and venous samples during CPR are higher than the pre-arrest arterial values.Peer reviewe

Endothelial glycocalyx during early reperfusion in patients undergoing cardiac surgery

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Heparin Dose and Point-of-Care Measurements of Hemostasis in Cardiac Surgery-Results of a Randomized Controlled Trial

Objective: High heparin doses during cardiopulmonary bypass (CPB) have been suggested to reduce thrombin activation and consumption coagulopathy and consequently bleeding complications. The authors investigated the effect of a high heparin dose during CPB on point-of-care measurements of coagulation. The authors hypothesized that during CPB a high heparin dose compared with a lower heparin dose would reduce thrombin generation and platelet activation and tested whether this would be reflected in the results of rotational thromboelastometry (TEM) and platelet aggregation, measured with multiple electrode aggregometry (MEA). Design: Prospective, randomized, controlled, open single-center study. Setting: University teaching hospital. Participants: Sixty-three consecutive patients undergoing elective coronary artery bypass grafting with CPB were enrolled. Interventions: Patients were randomly assigned to receive either a high (600 IU/kg, n = 32) or a low (300 IU/kg, n = 31) initial dose of heparin. Target levels of activated clotting time during CPB were >600 seconds in the high heparin dose group and >400 seconds in the low heparin dose group. Measurements and Main Results: Blood samples were collected (1) preoperatively after induction of anesthesia, (2) 10 minutes after aortic declamping, (3) 30 minutes after protamine administration, and (4) 3 hours after protamine administration. TEM and MEA were then measured. There was no difference in blood loss up to 18 hours postoperatively (median 735 mL for high dose v 610 mL for low dose; p <0.056) or transfusions between the groups. Total median heparin dose (54,300 IU v 27,000 IU; p = 0.001) and median antifactor Xa levels during CPB (9.38 U/mL v 5.04 U/mL; p = 0.001) were greater in the high than in the low heparin dose group. However, neither TEM nor MEA results differed significantly between the groups. Conclusions: Compared with a lower dose of heparin during CPB, a high dose of heparin had little effect on the point-of-care measurements of hemostasis, TEM, and MEA. Based on the similarity of platelet and coagulation activity assessments, the higher heparin dose does not appear to offer benefit during CPB. (C) 2020 Elsevier Inc. All rights reserved.Peer reviewe

The effect of 50% compared to 100% inspired oxygen fraction on brain oxygenation and post cardiac arrest mitochondrial function in experimental cardiac arrest

Background and aim: We hypothesised that the use of 50% compared to 100% oxygen maintains cerebral oxygenation and ameliorates the disturbance of cardiac mitochondrial respiration during cardiopulmonary resuscitation (CPR). Methods: Ventricular fibrillation (VF) was induced electrically in anaesthetised healthy adult pigs and left untreated for seven minutes followed by randomisation to manual ventilation with 50% or 100% oxygen and mechanical chest compressions (LUCAS (R)). Defibrillation was performed at thirteen minutes and repeated if necessary every two minutes with 1 mg intravenous adrenaline. Cerebral oxygenation was measured with near-infrared spectroscopy (rSO(2), INVOS (TM) 5100C Cerebral Oximeter) and with a probe (NEUROVENT-PTO, RAUMEDIC) in the frontal brain cortex (PbO2). Heart biopsies were obtained 20 min after the return of spontaneous circulation (ROSC) with an analysis of mitochondrial respiration (OROBOROS Instruments Corp., Innsbruck, Austria), and compared to four control animals without VF and CPR. Brain rSO(2) and PbO2 were log transformed and analysed with a mixed linear model and mitochondrial respiration with an analysis of variance. Results: Of the twenty pigs, one had a breach of protocol and was excluded, leaving nine pigs in the 50% group and ten in the 100% group. Return of spontaneous circulation (ROSC) was achieved in six pigs in the 50% group and eight in the 100% group. The rSO(2) (p = 0.007) was lower with FiO(2) 50%, but the PbO2 was not (p = 0.93). After ROSC there were significant interactions between time and FiO(2) regarding both rSO(2) (p = 0.001) and PbO2 (p = 0.004). Compared to the controls, mitochondrial respiration was decreased, with adenosine diphosphate (ADP) levels of 57 (17) pmol s(-1) mg(-1) compared to 92 (23) pmol s(-1) mg(-1) (p = 0.008), but there was no difference between different oxygen fractions (p = 0.79). Conclusions: The use of 50% oxygen during CPR results in lower cerebral oximetry values compared to 100% oxygen but there is no difference in brain tissue oxygen. Cardiac arrest disturbs cardiac mitochondrial respiration, but it is not alleviated with the use of 50% compared to 100% oxygen (Ethical and hospital approvals ESAVI/1077/04.10.07/2016 and HUS/215/2016, 7 30.3.2016, Funding Helsinki University and others). (C) 2017 Elsevier B.V. All rights reserved.Peer reviewe

The effects of intravenous lipid emulsion on hemodynamic recovery and myocardial cell mitochondrial function after bupivacaine toxicity in anesthetized pigs

Local anesthetic toxicity is thought to be mediated partly by inhibition of cardiac mitochondrial function. Intravenous (i.v.) lipid emulsion may overcome this energy depletion, but doses larger than currently recommended may be needed for rescue effect. In this randomized study with anesthetized pigs, we compared the effect of a large dose, 4 mL/kg, of i.v. 20% Intralipid (R) (n = 7) with Ringer's acetate (n = 6) on cardiovascular recovery after a cardiotoxic dose of bupivacaine. We also examined mitochondrial respiratory function in myocardial cell homogenates analyzed promptly after needle biopsies from the animals. Bupivacaine plasma concentrations were quantified from plasma samples. Arterial blood pressure recovered faster and systemic vascular resistance rose more rapidly after Intralipid than Ringer's acetate administration (p <0.0001), but Intralipid did not increase cardiac index or left ventricular ejection fraction. The lipid-based mitochondrial respiration was stimulated by approximately 30% after Intralipid (p <0.05) but unaffected by Ringer's acetate. The mean (standard deviation) area under the concentration-time curve (AUC) of total bupivacaine was greater after Intralipid (105.2 (13.6) mg.min/L) than after Ringer's acetate (88.1 (7.1) mg.min/L) (p = 0.019). After Intralipid, the AUC of the lipid-un-entrapped bupivacaine portion (97.0 (14.5) mg.min/L) was 8% lower than that of total bupivacaine (p <0.0001). To conclude, 4 mL/kg of Intralipid expedited cardiovascular recovery from bupivacaine cardiotoxicity mainly by increasing systemic vascular resistance. The increased myocardial mitochondrial respiration and bupivacaine entrapment after Intralipid did not improve cardiac function.Peer reviewe