Alexey Schramko

Rapidly Degradable Hydroxyethyl Starch Solutions Impair Blood Coagulation After Cardiac Surgery : A Prospective Randomized Trial

BACKGROUND: There is continuing concern about the effect of hydroxyethyl starch (HES) solutions on blood coagulation. Rapidly degradable HES solutions with more favorable effects on clot strength have therefore been developed. Because the risk of bleeding is increased after cardiopulmonary bypass, we examined whether these types of HES solutions could be administered after cardiac surgery without an alteration of coagulation. METHODS: Two new rapidly degradable HES solutions were compared with human albumin in 45 patients scheduled for elective primary cardiac surgery. After admission to the cardiac surgical intensive care unit, the patients were allocated in random order to receive either 15 mL/kg of HES solution with low molecular weight and low molar substitution (either 6% HES200/0.5 or 6% HES130/0.4) or 4% human albumin solution as a short-time (70–240 min) infusion. RESULTS: Clot formation time was prolonged and maximum clot firmness was decreased in thromboelastometry tracings after infusion of both HES solutions. This impairment in thromboelastometry tracings partly recovered (using InTEM® and ExTEM® coagulation activators) at 2 h after the completion of the study infusion. Platelet contribution to maximum clot firmness remained unaffected in all of the study groups. HES did not induce fibrinolysis. No changes in thromboelastometry tracings were observed after human albumin infusion. Chest tube drainage was comparable in the study groups. CONCLUSIONS: We conclude that a short-time infusion of rapidly degradable HES solutions after cardiac surgery produces impairment in fibrin formation and clot strength in thromboelastometry tracings. In this clinical setting, human albumin does not impair hemostasis.

Haemodynamics and acid-base equilibrium after cardiac surgery: comparison of rapidly degradable hydroxyethyl starch solutions and albumin.

Background: Stable haemodynamics is often achieved by administration of colloids after cardiac surgery. We conducted a prospective, randomized, open-label study comparing haemodynamics and acid-base equilibrium after infusion of two rapidly degradable hydroxyethyl starch (HES) solutions or human albumin (HA) to cardiac surgical patients. Materials and Methods: 45 patients received a predetermined fixed dose of 15 ml kg−1 of either 6% HES (MW 130 kDa, n=15), 6% HES (MW 200 kDa, n=15) or 4% HA (MW 69 kDa, n=15) after on-pump cardiac surgery. Results: Left ventricular filling pressures assessed using pulmonary artery catheter responded similarly in all groups. Mean (SD) cardiac index was higher in HES130 [3.5 1 min−1 m−2 (0.7)] and HES200 [3.5 1 min−1 m−2 (0.5)] than in HA [2.8 1 min−1 m−2 (0.6)] group after completion of infusion (P=0.002) but no differences were detected at 2 and 18 hours. Oxygen delivery increased in both HES groups but not in HA group. After cessation of infusion base excess was the most negative in HA group. At 2 hours mean (SD) base excess was higher in HWS130 [0 (1.32)] than in HES200 [-1.32 (2.27)] and HA [-2.3 (1.3)] group (P=0.002, between the groups). Conclusions: We conclude that the effect of albumin on cardiac performance is inferior than that of HES130 or HES200 in early postoperative phase after cardiac surgery. HES130 induces no alterations in acid-base equilibrium whereas a negative base excess was observed after HA infusion.

Comparison of the effect of 6% hydroxyethyl starch and gelatine on cardiac and stroke volume index: a randomized, controlled trial after cardiac surgery

Background and aims: The objective of this study was to find out the effect of various doses of hydroxyethyl starch (HES), gelatine or Ringer’s acetate on cardiac and stroke volume index after cardiac surgery. Material and methods: Three consecutive boluses (each 7 mL·kg-1) of either 6% HES 130/0.4, 4% gelatine, or Ringer’s acetate solutions were administered to 45 patients postoperatively. The rate of infusions was adjusted according to haemodynamic measurements. Thereafter, infusion of the study solution (7 mL·kg-1) was continued for the following 12 hours. The total dose of study solution was 28 mL·kg-1. Results and conclusion: Mean (SD) cardiac and stroke volume indices were greater in the HES group [2.8 L·min-1.m-2 (0.7), 34.1 (6.7) ml·m -2] than in the gelatine group [2.2 L·min-1.m -2 (0.6), 25.8 (7.2) ml·m-2] after completion of 7 mL·kg-1 of study solution. At this stage, the effect of gelatine did not differ from Ringer’s acetate. After completion of 14 mL·kg-1 and 21 mL·kg-1 of colloids, similar cardiac and stroke volume indices were observed and the haemodynamic response was better in both colloid groups than in the Ringer’s acetate group. No differences between groups were detected on the first postoperative morning. In the early postoperative phase after cardiac surgery, the effect of a single dose of HES solution on the haemodynamics was superior to the effect of gelatine or Ringer’s acetate. However, after repeated administration of the study solutions, the haemodynamics in the two colloid groups appeared to be similar, but superior to the Ringer’s acetate group.

The use of balanced HES 130/0.42 during complex cardiac surgery; effect on blood coagulation and fluid balance: a randomized controlled trial.

Introduction: Colloids and crystalloid are used during cardiac surgery for priming of the cardiopulmonary bypass (CPB) circuit. Colloids may decrease postoperative fluid balance because of their high oncotic pressure and low risk of fluid extravasation. On the other hand, colloids have been shown to impair blood coagulation. Materials and methods: In a prospective, randomized, double-blinded study, 50 patients scheduled for coronary artery bypass grafting or a valve procedure were planned to be randomized to receive either balanced 6% HES130/0.42 or Ringer-acetate solution for CPB priming. Randomization was stopped prematurely after 35 randomized patients (19 in the HES and 16 in the Ringer groups) because of the published report where HES130/0.42 was associated with impaired renal function. Effects on haemostasis and fluid balance were investigated. Results: The rotational thromboelastometry (ROTEM®) parameters and chest tube drainage on the first postoperative morning (1POM) were comparable between the groups (p>0.05). However, patients in the HES group needed more blood and blood product transfusions. The total volume administered into the CPB circuit was lower in the HES than in the Ringer (RIN) group, 2905±1049 mL versus 3973±1207 mL (p=0.011), but there was no statistically significant difference in total fluid balance on the 1POM (5086±1660 mL in the HES group versus 5850±1514 mL in the RIN group, respectively). Conclusions: After complex cardiac surgery, the use of balanced 6% HES130/0.42 solution for CPB circuit priming did not impair haemostasis measured by ROTEM®, but it increased the need for transfusions. Fluid balance after CPB was less positive in the HES group, but, on the 1POM, it was comparable between the groups.

Effect of the combination of mannitol and ringer acetate or hydroxyethyl starch on whole blood coagulation in vitro.

Mannitol is administered to decrease the intracranial pressure and to improve surgical conditions during craniotomy. Simultaneously a crystalloid infusion is always given and sometimes hydroxyethyl starch (HES) is indicated for intravascular volume replacement. As normal coagulation profile is required during craniotomy, we aimed at determining the effect of mannitol with or without HES or Ringer acetate on blood coagulation in this randomized cross-over in vitro study. Blood samples were withdrawn from 10 volunteers. From whole blood we prepared 10 vol.% and 20 vol.% dilutions of mannitol (15% Mannitol) alone, mannitol and Ringer acetate, and mannitol and HES 130/0.4 (Voluven) at a ratio of 1:1. Blood samples were analyzed by modified thromboelastometry. Coagulation parameters: clotting time, clot formation time, and maximum clot firmness (MCF), were registered. Clot formation time was prolonged in all dilutions compared with control (P<0.05). MCF decreased in all dilutions compared with control (P<0.05). MCF in 20 vol.% dilution of mannitol with HES was lower than MCF in the corresponding dilution with Ringer acetate (P<0.05). Fibrinogen-dependent MCF in 10 vol.% dilution of mannitol with HES was lower than MCF in the corresponding dilution with Ringer acetate (P<0.05). We conclude that mannitol in combination with HES 130/0.4 impairs clot propagation and clot strength in vitro. Fibrin clot strength impairment is more pronounced when mannitol is combined with HES than Ringer acetate. Our findings indicate that HES in combination with mannitol should be avoided whenever a disturbance in hemostasis is suspected during craniotomy.

Effects of combined balanced colloid and crystalloid on rotational thromboelastometry in vitro.

Our objective was to investigate the in vitro effects of a totally balanced fluid concept on whole blood coagulation. Venous blood from 12 healthy volunteers was diluted by 20% and 40% with a combination of an equal amount of colloid (balanced or unbalanced 6% HES 130/0.4, or 4% gelatin) and crystalloid (balanced or unbalanced Ringer’s acetate). Blood samples were analyzed with rotational thromboelastometry (ROTEM®). The initiation of coagulation was delayed in all dilutions except for the 20 vol% gelatin-dilution. In the extrinsic activation test, maximum clot firmness was decreased and clot formation time prolonged after 40 vol% hemodilution with a balanced Ringer’s/unbalanced HES combination, more than in the corresponding gelatin hemodilution. In the fibrin-based test, after both 20- and 40 vol% hemodilution with unbalanced Ringer’s/gelatin solution, maximum clot firmness was significantly stronger than in the Ringer’s/HES-combinations. The combination of balanced colloid and crystalloid has similar coagulation effects in vitro as their respective combination of unbalanced solutions.

Prone Versus Sitting Position in Neurosurgery—Differences in Patients' Hemodynamic Management

OBJECTIVEnNeurosurgery in general anesthesia exposes patients to hemodynamic alterations in both the prone and the sitting position. We aimed to evaluate the hemodynamic profile during stroke volume-directed fluid administration in patients undergoing neurosurgery either in the sitting or the prone position.nnnMETHODSnIn 2 separate prospective trials, 30 patients in prone and 28 patients in sitting position were randomly assigned to receive either Ringer acetate (RAC) or hydroxyethyl starch (HES; 130 kDa/0.4) for optimization of stroke volume. After combining data from these 2 trials, 2-way analysis of variance was performed to compare patients hemodynamic profile between the 2 positions and to evaluate differences between RAC and HES consumption.nnnRESULTSnTo achieve comparable hemodynamics during surgery, a higher mean cumulative dose of RAC than HES was needed (679 mL ± 390 vs. 455 mL ± 253; P < 0.05). When fluid consumption was adjusted with weight, statistical difference was lost. Fluid administration did not differ between the prone and sitting position. Mean arterial pressure was lower and cardiac index and stroke volume index were higher over time in patients in the sitting position.nnnCONCLUSIONSnThe sitting position does not require excess fluid treatment compared with the prone position. HES is slightly more effective than RAC in achieving comparable hemodynamics, but the difference might be explained by patient weight. With goal-directed fluid administration and moderate use of vasoactive drugs, it is possible to achieve stable hemodynamics in both positions.

Albumin-Beyond Fluid Replacement in Cardiopulmonary Bypass Surgery: Why, How, and When?

Maintaining vascular barrier competence, preventing interstitial edema, and keeping microcirculation intact is crucial to achieve an optimal outcome in cardiopulmonary bypass surgery (CPB). Blood contact with roller pumps and foreign surfaces during CPB induces shear stress and a pressure drop across the pump boot that leads to transient systemic activation of the inflammatory and hemostatic systems. Moreover, patients after CPB often need volume resuscitation using the smallest possible amount of colloid solution because of fluid overload. For this purpose, human-derived albumin may be preferred over synthetic colloids because CPB priming with albumin preserves oncotic pressure, prevents platelet adhesion, and likely induces less consumption of coagulation factors. In patients with increased bleeding or renal failure, albumin is a safe alternative because of its minimal side effects. Large, randomized clinical trials comparing the benefit of albumin versus other fluids are warranted in the future to define albumin’s distinct role in select high-risk surgical populations.

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® (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.

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

OBJECTIVEnAnemia 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).nnnDESIGNnProspective randomized trial.nnnTYPE OF HOSPITALnUniversity Hospital of Helsinki, Finland.nnnPARTICIPANTSnEighty patients with written informed consent, scheduled for elective open-heart surgery were randomized in 2 groups.nnnINTERVENTIONSnTwo 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.nnnMEASUREMENTS AND MAIN RESULTSnRotational 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.nnnCONCLUSIONnHb 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.