Engelbert Deusch

The Effects of High Molecular Weight Hydroxyethyl Starch Solutions on Platelets

Physicochemical characteristics of hydroxyethyl starch (HES) molecules determine their side effects on hemostasis. Our aim in the present experiments was to test the antiplatelet effect of novel high molecular weight HES. Citrated whole blood was hemodiluted in vitro (0% and 20%) with either HES 550 (Hextend®), HES 600 (6%Hetastarch-Baxter®), HES 200 (Elohäst®), or the solvent of Hextend® in its commercially available solution. The availability of glycoprotein IIb–IIIa was assessed on nonstimulated and on agonist-induced platelets using flow cytometry. Glycoprotein IIb–IIIa availability increased significantly after hemodilution with Hextend® and its solvent by 23% and 24%, respectively, but decreased in the presence of 6% Hetastarch-Baxter® and Elohäst® by 18% and 15%, respectively, with no significant difference between the latter two colloids. This study shows that Hextend® does not inhibit platelet function as anticipated by its high molecular weight and degree of substitution. The unexpected platelet stimulating effect of Hextend® is unique among the currently available HES preparations and may, at least in part, be induced by its solvent containing calcium chloride dihydrate (2.5 mmol/L). The platelet-inhibiting effect of 6%Hetastarch-Baxter® was not significantly different from that of medium molecular weight HES 200.

The procoagulatory effects of delta-9-tetrahydrocannabinol in human platelets.

Delta-9-tetrahydrocannabinol (THC) is increasingly used for the long-term treatment of nausea, vomiting, cachexia, and chronic pain. Recent reports, however, have indicated an increased risk of myocardial infarction and thromboangiitis obliterans after THC intake. Blood platelets have an essential role in the pathogenesis of these two diseases, but it is unclear whether platelets are potential target cells for cannabinoids. We investigated the effects of THC on human platelets and the expression of cannabinoid receptors on their cell membranes in this in vitro study. The effects of THC (final concentrations 10−7 to 10−5 M) on the expression of activated platelet fibrinogen receptor (glycoprotein IIb-IIIa) and P selectin were characterized by flow cytometry. Western blotting was performed with platelet membrane preparations to determine the surface expression of cannabinoid receptors on human platelets. THC increased the expression of glycoprotein IIb-IIIa and P selectin on human platelets in a concentration-dependent manner. The two known cannabinoid receptors (CB1 and CB2) were both detected on the cell membrane of human platelets. Our functional results may suggest a receptor-dependent pathway of THC-induced platelet activation. However, further in vivo studies are warranted to evaluate the role of cannabinoid receptors in mediating the demonstrated procoagulatory effect of THC.

Inhibition of Platelet Function by Hydroxyethyl Starch Solutions in Chronic Pain Patients Undergoing Peridural Anesthesia

The use of hydroxyethyl starch (HES) solutions as a fluid replacement before peridural blockade may compromise blood coagulation, thus increasing the risk of neuraxial bleeding. In this prospective, double-blind, placebo-controlled, crossover study, we compared the influence of HES 130 (molecular weight in kilodalton), HES 200, and lactated Ringers solution on platelet function and hemodynamics in chronic low back pain patients scheduled for peridural blockades. Patients received 3 test infusions of 10 mL/kg each administered IV for 30 min. Collagen/epinephrine and collagen/adenosine diphosphate were used as agonists for assessment of platelet function analyzer-closure times. Arterial blood pressure, heart rate, platelet counts, and hemoglobin levels were documented. Platelet function analyzer-closure times remained stable after lactated Ringers solution but were significantly prolonged after HES. The platelet-inhibiting effect of HES 200 was more than that of HES 130. Hemodynamic stability was sufficiently maintained by all test infusions. In contrast to previous observations, a relevant antiplatelet effect of both low and medium molecular weight HES solutions was found in this study in chronic pain patients undergoing peridural anesthesia. Because hemostasiological competence is a prerequisite for safe neuraxial blockade, the decision of HES for intravascular fluid administration before blockade should be critically made.

Point-of-care platelet function tests: detection of platelet inhibition induced by nonopioid analgesic drugs.

Detection of platelet inhibition is of clinical relevance in the preinterventional risk–benefit assessment in chronic low-back-pain patients scheduled for invasive pain therapy. We evaluated the sensitivity of various point-of-care platelet function tests for the detection of platelet inhibition induced by nonopioid analgesic drugs. After Institutional Review Board approval and informed consent, citrated whole blood from 40 patients with chronic unspecific low back pain was investigated before and 30 min after intravenous infusion of the study medication consisting of diclofenac 75 mg (plus orphenadrin 30 mg; Neodolpasse; Fresenius Kabi Austria GmbH, Austria), parecoxib 40 mg (Dynastat; Pharmacia Europe EEIG, UK), paracetamol 1 g (Perfalgan; Bieffe Medital S.P.A., Italy), or normal saline in a randomized, cross-over, double-blinded, placebo-controlled study. Platelet function was assessed using the PFA-100 platelet function analyzer and thromboelastometry, as well as impedance aggregometry (in the last 17 patients recruited after it became commercially available). Sensitivity for detecting diclofenac-induced platelet inhibition was 85% for the PFA-100 using epinephrine as agonist and 94% for arachidonic acid-induced impedance aggregometry. ADP-induced platelet function tests, as well as cytochalasin D-modified thromboelastometry were unreliable. All tests had a low incidence of false-positive test results after normal saline. Paracetamol and parecoxib had no significant platelet inhibiting effect. The PFA-100 using epinephrine as agonist and arachidonic acid-induced impedance aggregometry are recommended for the detection of cyclooxygenase-I-inhibiting effects of nonsteroidal anti-inflammatory drugs such as diclofenac. Our findings confirm that a single rescue dose of paracetamol and parecoxib has no antiplatelet effect.

Low predictability of three different noninvasive methods to determine fluid responsiveness in critically ill children.

Objective: To predict fluid responsiveness by noninvasive methods in a pediatric critical care population. Design: Prospective observational clinical trial. Setting: PICU in a tertiary care academic hospital. Patients: Thirty-one pediatric patients aged from 1 day to 13 years under mechanical ventilation and on catecholamine support. Interventions: We tested three noninvasive methods to predict fluid responsiveness: an esophageal Doppler system (CardioQ), a pulse contour analysis algorithm system (LiDCOrapid), and respiratory variations in vena cava inferior diameter. Stroke volume index was measured by transthoracic echocardiography before and after fluid challenge to determine fluid responders. Infusion of 10 mL/kg hydroxyethylstarch 130/0.4. Measurements and Main Results: Predictability of fluid responsiveness was only found in Doppler peak velocity of descending aortal blood flow. Increased peak velocity with reduction after fluid bolus was predictive for nonresponding to IV fluid challenge. Sensitivity and specificity of peak velocity were 69% and 73%, respectively. The cut point was set at 135.5 cm/s. The lower the Doppler peak velocity, the higher was the probability for a fluid response. Neither stroke volume variations nor respiratory variations in vena cava inferior diameter during mechanical ventilation were useful in predicting fluid responsiveness in this pediatric patient population. None of the children had abdominal hypertension measured by bladder pressure. Conclusions: Dynamic preload variables such as stroke volume variation or respiratory variations in vena cava inferior diameter may not be useful for predicting fluid responsiveness in certain pediatric patient populations. Esophageal Doppler peak velocity was predictive of fluid responsiveness where a target value of more than 135,5 cm/s may be a signal to terminate further fluid challenges. This target value may be different in different age groups, as esophageal Doppler peak velocity varies with age.

The mechanical properties of continuous spinal small-bore catheters.

Continuous spinal anesthesia (CSA) has a nearly 100-yr history. In situations of difficult removal of a CSA small-bore catheter, mechanical properties of the different catheters might be important, because breakage could occur. We compared 5 different CSA small-bore catheters, 22- to 28-gauge from 3 manufacturers, for tensile strength, tensile stress, distension, and yield strength. Maximal tensile strength is the force applied before breakage of the catheter. The material characteristics of different CSA small-bore catheters for maximal tensile strength were: 22-gauge = 29.56 ± 1.56 (mean ± sd) Newton (N), 24-gauge = 16.77 ± 1.61 N, 25-gauge = 9.20 ± 0.48 N, 27-gauge = 4.61 ± 0.25 N, 28-gauge = 5.07 ± 0.59 N at room temperature. A strong correlation between maximal tensile strength and the outer diameter (r = 0.957, P < 0.001) and maximal tensile strength and the wall thickness (r = 0.9, P < 0.001) was observed. Although extrapolation from experimental studies to clinical routine should be made with care, our data suggest that catheters with higher-strength characteristics may reduce the risk of catheter breakage in patients, although clinical correlations are lacking.

Inhalational sevoflurane in severe bronchial obstruction unresponsive to multipharmacologic therapy: a case report.

Introduction: Bronchial asthma with respiratory failure is a challenge for the intensivist as mechanical ventilation is often difficult due to bronchoconstriction and air-trapping. We describe a case of severe asthma with respiratory acidosis in a 10-year-old patient unresponsive to multipharmacologic broncholytic therapy. Only the initiation of sevoflurane inhalation resolved severe bronchoconstriction and dynamic hyperinflation, leading to complete recovery. Case presentation: A 10-year-old Caucasian boy was intubated and mechanically ventilated due to an asthmatic attack. Bronchoconstriction and dynamic hyperinflation were severe while multipharmacological broncholytic therapy was unsuccessful. Inhalation with sevoflurane via an anaesthesia machine was the key intervention leading to gradual resolving of severe hypercapnia and respiratory acidosis. Furthermore bilateral pupil dilation occurred during hypercapnia, but no intracranial pathology could be detected. The patient made an uneventful recovery. To our knowledge this is the first case where hypercapnia and respiratory acidosis were so profound and long lasting yet the patient survived without any damage. Conclusions: Inhalational anaesthetics must be considered as an early treatment option in ventilated asthmatic patients with bronchial obstruction unresponsive to conventional therapy even though their administration in intensive care units may be difficult.