Michael Felfernig

The effects of hydroxyethyl starches of varying molecular weights on platelet function

We evaluated the effect of various hydroxyethyl starch (HES) solutions on platelet function. Blood was obtained before and after the IV infusion (10 mL/kg) of saline (n = 10), HES 70/0.5–0.55 (molecular weight in kD/degree of substitution;n = 10), HES 130/0.38–0.45 (n = 10), HES 200/0.6–0.66 (n = 10), or HES 450/0.7–0.8 (n = 10) in otherwise healthy patients scheduled for elective surgery. Collagen and epinephrine were used as agonists for assessment of platelet function analyzer closure times. Flow cytometry was used to assess agonist-induced expression of activated glycoprotein IIb/IIIa complex and P-selectin. Infusion of HES 450/0.7–0.8, HES 200/0.6–0.66, and HES 70/0.5–0.55 prolonged closure times and reduced glycoprotein IIb/IIIa expression, whereas saline and HES 130/0.38–0.45 had no significant effect on platelet variables. P selectin expression was not affected by any solution tested. In vitro experiments demonstrated a less inhibiting effect of HES 130/0.38–0.45 on closure times when compared with other HES solutions. This study shows that HES 450/0.7–0.8, HES 200/0.6–0.66, and HES 70/0.5–0.55 inhibit platelet function by reducing the availability of the functional receptor for fibrinogen on the platelet surface. Our data indicate that fluid resuscitation with HES 130/0.38–0.45 may reduce the risk of bleeding associated with synthetic colloids of higher molecular weight and degree of substitution.

Ilioinguinal/iliohypogastric blocks in children: where do we administer the local anesthetic without direct visualization?

BACKGROUND:Ultrasonographic observation of peripheral nerve blocks enables direct visualization of the spread of local anesthetic around the targeted nerves. Similarly, ultrasonography may be used to determine the site of local anesthetic placement when landmark-based techniques are used. We performed a study to determine the actual location of local anesthetic when ilioinguinal/iliohypogastric nerve blocks are performed using landmark-based techniques in children in an attempt to explain a failed block. METHODS:After induction of general anesthesia (1 minimum alveolar anesthetic concentration halothane and laryngeal mask airway), 62 children scheduled for inguinal surgery received an ilioinguinal/iliohypogastric nerve block based on standard anatomical landmarks. Ultrasonography was then used to determine the actual location of local anesthetic placement. The anesthesiologist performing the block was blinded to the ultrasonographic investigation. Successful blocks were recorded either when the local anesthetic surrounded the nerves or were based on clinical signs after skin incision. RESULTS:In 14% of the blocks, the local anesthetic was administered correctly around the nerves resulting in successful blocks. In the remaining 86%, the local anesthetic was administered in adjacent anatomical structures (iliac muscle 18%, transverse abdominal muscle 26%, internal oblique abdominal muscle 29%, external oblique abdominal muscle 9%, subcutaneous 2%, and peritoneum 2%), and 45% of these blocks failed. CONCLUSION:Accurate placement of local anesthetic around the ilioinguinal/iliohypogastric nerves in children is seldom possible when landmark-based techniques are used. In the majority of patients, the local anesthetic was inaccurately placed in adjacent anatomical structures with unpredictable block results.

Anticoagulation with prostacyclin and heparin during continuous venovenous hemofiltration.

Objectives: To investigate anticoagulation with prostacyclin (prostaglandin I2 [PGI2]) and/or heparin during continuous venovenous hemofiltration, and the role of in vitro tests of primary hemostasis in controlling anticoagulation. Design: Prospective, randomized, controlled trial. Setting: Intensive care unit. Patients: Forty‐six consecutive, critically ill, mechanically ventilated patients with postoperative acute renal failure. Interventions: Anticoagulation of the patients blood was accomplished using heparin (6.0 ± 0.3 IU/kg/hr for group 1), PGI2 (7.7 ± 0.7 ng/kg/min for group 2), or both PGI2 and heparin (6.4 ± 0.3 ng/kg/min, 5.0 ± 0.4 IU/kg/hr, respectively, for group 3), administered into the extracorporeal line before the hemofilter during continuous venovenous hemofiltration. Measurements and Main Results: After Ethics Committee approval and informed consent were obtained, tests of primary and secondary hemostasis, plasma concentrations of 6‐ketoprostaglandin F1&agr; (by radioimmunoassay), and hemodynamic measurements were performed before hemofiltration and 24 hrs after hemofiltration. In groups 1 and 3, hemodynamic parameters remained stable, whereas in group 2 (the PGI2 group), there were significant reductions in systemic and pulmonary vascular resistances and mean arterial pressure. Platelet function was unchanged in group 1, and was inhibited in groups 2 and 3. Corresponding with the prolongation of in vitro bleeding time, the 6‐ketoprostaglandin F1&agr; concentration was increased, indicating an effective inhibition of platelet aggregation within the hemofilter. Platelet counts remained stable in all patients. Plasma coagulation tests were stable in groups 2 and 3, and were prolonged in group 1. In all patients, no major bleeding complications were observed and there was no clinically important bleeding. Mean hemofilter duration lasted longest in group 3. Blood urea nitrogen and circulating creatinine concentrations decreased significantly in groups 2 and 3 within the study period. Conclusions: Patients receiving both PGI2 and heparin showed better hemodynamic profiles and enhanced hemofilter duration compared with the other groups and no bleeding complications were observed. Therefore, we recommend anticoagulation with PGI2 and heparin during continuous venovenous hemofiltration with close monitoring of platelet function, coagulation profile, and overall hemodynamics. (Crit Care Med 1994; 22:1774–1781)

The effect of hydroxyethyl starch 200 kD on platelet function.

We evaluated the effects of hydroxyethyl starch with a molecular weight of 200 kD (HES 200 kD) on platelets to gain insight into the potential mechanisms involved in the anticoagulant effects of HES 200 kD. Blood was obtained before and after an IV infusion (10 mL/kg) of either saline (n = 15) or HES 200 kD (n = 15) in otherwise healthy patients scheduled for minor elective surgery. Flow cytometry was used to assess the expression of glycoprotein (GP) IIb-IIIa, GP Ib, and P-selectin on agonist-activated platelets. Overall platelet function was evaluated by assessing thromboelastographic maximum amplitude (MA) in celite-activated blood and platelet function analyzer-closure times by using collagen/adenosine diphosphate cartridges. Saline infusion had no effects on platelet variables, whereas HES 200 kD reduced GP IIb-IIIa expression and MA and prolonged platelet function analyzer-closure times, without affecting the expression of P-selectin and GP Ib. In vitro experiments extended these observations by a concentration-related inhibiting effect of HES 200 kD on GP IIb-IIIa expression. This study demonstrates that cellular abnormalities with decreased availability of platelet GP IIb-IIIa are involved in the anticoagulant effects of HES 200 kD. Implications The present data indicate that an antiplatelet effect of hydroxyethyl starch 200 kD should be considered during plasma volume expansion with this synthetic colloid.

Endogenous Heparin-Like Substances Significantly Impair Coagulation in Patients Undergoing Orthotopic liver Transplantation

Orthotopic liver transplantation (OLT) is associated with severe bleeding, especially after reperfusion of the grafted liver.Heparin released from the liver graft contributes to postreperfusion coagulopathy. Although patients with liver cirrhosis have increased levels of endogenous heparinoids, the role of these substances during liver transplantation is unclear. Therefore, we performed native and heparinase-modified thrombelastography (TEG) in 72 patients undergoing OLT. TEG was performed at skin incision, 10 min before and 10 min after clamping of the vena cava, 10 min before and 10 min after graft perfusion, and at the end of surgery. Heparinase-modified TEG compared with native TEG demonstrated heparin activity. In contrast to other investigations, we found significant heparin effects before reperfusion, although patients received no exogenous heparin. These heparin effects were greater in patients with cirrhosis compared with patients with cancer as the underlying disease leading to OLT. Administration of coagulation factors is the usual treatment of coagulopathies during OLT. The comparison of native versus heparinase-modified TEG can distinguish between heparin activity or coagulation factor deficiency as a cause of bleeding complications and provides a rational approach to the treatment of bleeding during OLT. Implications: Impaired coagulation function, contributed to by heparin or heparin-like substances, is frequently observed after reperfusion of a transplanted liver. This study demonstrates that a heparinase-modified thrombelastography can identify significant heparin effects in the absence of exogenous heparin administration in patients undergoing liver transplantation. (Anesth Analg 1998;86:691-5)

The effects of hydroxyethyl starch solutions on thromboelastography in preoperative male patients

Background: Hydroxyethyl starches (HES) have been shown to decrease clot strength and to increase coagulation times assessed by thromboelastography (TEG). HES with minimal anticoagulant side‐effects is beneficial for plasma volume expansion in the perioperative setting. A comparison of the in vivo effects of high, middle and low molecular weight HES solutions on TEG variables has not been performed so far.

Effect of prostacyclin on platelets, polymorphonuclear cells, and heterotypic cell aggregation during hemofiltration*

ObjectivesHemodialysis activates both platelets and leukocytes, which play a role in the development of multiple organ dysfunctions in critically ill patients. Prostacyclin inhibits both cell types in vitro. To examine the hypothesis that prostacyclin prevents cellular activation during clinical hemofiltration, we investigated the expression of activation markers on platelets and leukocytes using whole blood flow cytometry. DesignProspective, randomized, double-blind, controlled trial. SettingIntensive care unit. PatientsA total of 24 consecutive, critically ill, mechanically ventilated patients with acute renal failure secondary to sepsis or major surgery. InterventionsFor anticoagulation during hemofiltration, patients received either unfractionated heparin or unfractionated heparin and prostacyclin (5 ng·kg−1·min−1). Anticoagulants were administered into the extracorporeal circuit before the hemofilter. Blood samples were obtained from an arterial catheter before hemofiltration and from the inlet and outlet lines of the extracorporeal circuit at 1 and 24 hrs during hemofiltration. Measurements and Main ResultsExpression of GP IIb–IIIa and P-selectin on adenosine diphosphate-activated platelets and platelet-leukocyte aggregation were significantly lower after the passage of blood through the hemofilter in patients receiving an extracorporeal infusion of prostacyclin plus heparin when compared with control patients receiving heparin only. There were no statistically significant differences in the expression of CD11b on leukocytes between the two groups. ConclusionsThese findings suggest that prostacyclin reversibly inhibits platelet function by diminishing the expression of platelet fibrinogen receptors and P-selectin and reduces heterotypic platelet-leukocyte aggregation during clinical hemofiltration. However, prostacyclin fails to inhibit leukocyte activation at clinically relevant doses.

The effect of hydroxyethyl starch on platelet aggregation in vitro

The effect of hydroxyethyl starch (HES) on hemostasis seems to be minimal when it is used in recommended amounts.A number of studies have investigated the effect of HES on platelet function when administered in vivo, but there has been no study investigating the effect on the isolated platelet function when administered in vitro. A photometrical method to assess platelet function in platelet-rich plasma (approximately 250 x 109 platelets/L) was used with platelet aggregation induced using either collagen, epinephrine, adenosine diphosphate, or ristocetin. We found a dose-dependent decrease of platelet aggregation in vitro with either collagen or epinephrine, but not with adenosine diphosphate or ristocetin. However, the changes of HES on platelet aggregation were detected only in doses larger than those routinely used in the clinical setting. Therefore, we conclude that the influence of HES at the recommended doses on initial platelet aggregation may not be clinically relevant. Implications: The effect of hydroxyethyl starch on platelet function and coagulation is discussed. This study showed no influence on platelets in clinically relevant doses in an in vitro model. (Anesth Analg 1998;86:1318-21)

Early Detection of Preeclampsia by Determination of Platelet Aggregability

Preeclampsia is still a leading cause of maternal and fetal morbidity and mortality. There is evidence for the involvement of platelets. Therefore, we investigated the suitability of corrected whole blood impedance aggregometry as an early predictor of preeclampsia in 71 consecutive, high-risk pregnancies. According to the occurrence of preeclampsia, defined postpartum by an independent investigator, and the stage of pregnancy (early and late, cutoff: 25 weeks of gestation), four study groups were defined. Platelet aggregation data were corrected for the influence of hematocrit and platelet count by a special purpose software package. Women developing preeclampsia showed significantly higher platelet aggregation response compared to controls in early and late pregnancy. In early pregnancy, all women developing preeclampsia had aggregation responses to collagen higher than the highest responses among the controls. Hence, this test had a 100% positive predictive value of subsequent preeclampsia. Despite being significantly increased, platelet aggregability was of minor predictive value in late pregnancy. We conclude that preeclampsia is accompanied by exaggerated platelet aggregability, particularly perceptible early in the course of pregnancy. We propose collagen-induced whole blood platelet aggregation with correction for the influence of hematocrit and platelet count for early detection of preeclampsia.

Propofol without muscle relaxants for conventional or fiberoptic nasotracheal intubation: a dose-finding study.

UNLABELLED Endotracheal intubation has been performed during the administration of propofol anesthesia without neuromuscular blockade. In this study, we determined the propofol dose required for conventional nasotracheal or for fiberoptic nasotracheal intubation of all patients. Thirty-two patients undergoing maxillofacial surgery were randomly assigned to the conventional (n = 16) or to the fiberoptic (n = 16) intubation group. In both groups, anesthesia was induced by using IV fentanyl and IV titrated propofol according to clinical need (spontaneous respiration rate, verbal response). An endotracheal tube was placed nasally in the pharynx and the vocal cords visualized by using a fiberscope inserted via the tube. In the conventional group, the larynx was visualized additionally with a laryngoscope blade (Miller). In both groups propofol was titrated until the vocal cords opened. Patients were tracheally intubated, and the propofol dose was recorded. In all patients, the trachea could be intubated without the use of muscle relaxants. Considerable interindividual differences of dose requirements were observed. The amount of propofol required in the conventional group was significantly (P < 0.0001) larger (median +/- SD: 2.74 +/- 1.59 mg/kg; range 1.95-7.07 mg/kg) than in the fiberoptic group (1.37 +/- 0.59 mg/kg; 0.72-2.86 mg/kg). Hemodynamics remained stable in all patients. Postintubational hoarseness occurred in three patients of each group. Fiberoptic nasal intubation without a muscle relaxant can be facilitated with significantly smaller and more predictable dosages of propofol than conventional nasal endotracheal intubation. The possibility of titrating the propofol dose under assisted ventilation until the vocal cords open during fiberoptic nasotracheal intubation and the better predictability of the required dose favors the fiberoptic approach. IMPLICATIONS In this study, contrary to all preceding studies using predefined doses of propofol and opioids, we determined the minimal required propofol dose in combination with fentanyl for conventional or fiberoptic nasotracheal intubation without muscle relaxants.