Reliability of the heparin management test for monitoring high levels of unfractionated heparin: in vitro findings in volunteers versus in vivo findings during cardiopulmonary bypass

BACKGROUND: The authors assessed the heparin management test in vitro in volunteers and in vivo during cardiopulmonary bypass. METHODS: In vitro, the heparin management test was analyzed for heparin levels between 0 and 6 IU/ml using variations in hematocrit, platelets, procoagulants, and storage time. The in vivostudies consisted of two groups: In group I (cardiopulmonary bypass /= 180 min, with aprotinin) included use (n = 10) and nonuse of coumadin (n = 10) and anticoagulation according to the automated heparin dose-response assay. Tests were performed in duplicate (whole blood, two heparin management test analyzers) and compared with anti-Xa activity (plasma). RESULTS: In vitro, the results of the heparin management test (n = 1,070) correlated well with heparin concentration (r2 = 0.98). Dilution and storage time did not affect the heparin management test; a hematocrit of 60% and reduced procoagulants (10%) prolonged clotting time. In vivo, the correlation (heparin management test vs. anti-Xa) was strong in group I (r2 = 0.97 [with aprotinin] and 0.96 [without aprotinin]; n = 960) and group II without coumadin (r2 = 0.89, n = 516). In group II with coumadin, the overall correlation was r2 = 0.87 and 0.79 (n = 484), although the range varied widely (0.57-0.94, between-analyzer differences 0-47%). CONCLUSIONS: The results of the heparin management test were influenced by hematocrit, plasma coagulation factors, and the heparin level, but not by use of aprotinin. The heparin management test provided reliable values in vitro in group I, and in group II without coumadin but was less reliable in group II with coumadin.     

Traumatische Karotisdissektion

Traumatic dissection of the carotid artery is an easily overlooked consequence of trauma with notable morbidity and mortality which can be observed in up to 4?% of cases involving multiple trauma. Certain mechanisms and patterns of injury as well as specific symptoms should serve as indicators of a dissection and should therefore result in further diagnostic measures. An early diagnosis is of major relevance. This report describes the case of a 45-year-old victim of a traffic accident who showed symptoms of a dissection which had initially not been diagnosed.     

Anticoagulation during cardiopulmonary bypass in patients with heparin-induced thrombocytopenia type II and renal impairment using heparin and the platelet glycoprotein IIb-IIIa antagonist tirofiban

BACKGROUND: Patients with heparin-induced thrombocytopenia type II require an alternative to standard heparin anticoagulation. However, in patients with renal impairment, anticoagulation during cardiopulmonary bypass with agents such as danaparoid sodium or r-hirudin are associated with hemorrhage. Anticoagulation with unfractionated heparins combined with prostacyclin, a potent platelet aggregation inhibitor, is associated with severe hypotension. The authors investigated a new concept using unfractionated heparins after platelet inhibition with the short-acting platelet glycoprotein IIb-IIIa antagonist tirofiban. METHODS: Ten patients with heparin-induced thrombocytopenia type II and renal impairment were enrolled in the investigation. All had heparin-induced thrombocytopenia type II antibodies present as proved by the heparin-induced platelet aggregation assay, the heparin-platelet factor 4 enzyme-linked immunosorbent assay, or both. In all patients, preoperative anticoagulation to an activated partial thromboplastin time of 40-60 s was performed with r-hirudin. Anticoagulation during cardiopulmonary bypass was achieved with a bolus of 400 IU/kg unfractionated heparins after a bolus of tirofiban 10 microg/kg followed by an infusion of tirofiban at a rate of 0.15 microg x kg(-1) x min(-1) until 1 h before conclusion of cardiopulmonary bypass. Additional unfractionated heparins were only administered if activated clotting time decreased below 480 s. Coagulation was monitored by a abciximab-modified TEG and the adenosine diphosphate-stimulated (20 microm) platelet aggregometry. D-dimer concentrations, as a marker of venous thromboembolism, were measured before and 12, 24, and 48 h after surgery. Postoperative antithrombotic therapy was started immediately with r-hirudin to anticoagulation to an activated partial thromboplastin time of 40-60 s. RESULTS: The postoperative blood loss ranged from 110 to 520 ml. No patient needed reexploration. In no patient was there clinical evidence of thrombosis or embolism in the postoperative period or of a critical increase of the D-dimer concentrations, suggesting venous thromboembolism. Transfusion of platelets was necessary in only two patients. CONCLUSIONS: The protocol is easy to perform and no increased postoperative bleeding and no thromboembolic complications occurred. The combination of unfractionated heparins and tirofiban may be an alternative to other anticoagulation strategies in patients with heparin-induced thrombocytopenia.     

Assessing errors in the determination of base excess

We compared estimates for base excess of extracellular fluid (BE(ecf); mmol/L) obtained in five clinically used blood gas analyzers: AVL Compact 2 (Roche Diagnostics, Mannheim, Germany), Ciba-Corning 860 (Bayer Diagnostics, Fernwald, Germany), IL 1620 (Instrumentation Laboratories, Lexington, MA), Stat Profile Ultra (Nova Biomedical, Waltham, MA), and ABL 510 (Radiometer, Copenhagen, Denmark). A total of 134 measurements per analyzer were obtained in arterial and venous blood samples from 10 patients undergoing cardiac surgery and 65 measurements per analyzer in venous blood samples from 2 healthy volunteers. The blood samples were equilibrated in a tonometer with gases of known composition (37 degrees C). Additional theoretical studies were performed to evaluate the relationship between pH and calculated BE(ecf) value (with varied PCO(2)) using the formulas of the various analyzers. The standard deviations of repeated measurements were 0.24 mmol/L for ABL 510 and approximately 0.45 mmol/L for the other 4 analyzers. The maximal systematic difference between the average of all measurements of each analyzer was 3.7 mmol/L; this was primarily attributable to differences in measuring pH, and, to a lesser extent, to differences in calculation and determination of PCO(2). Comparison of the results from samples with different oxygen saturation showed that the relative alkalinity of deoxygenated hemoglobin (Haldane effect) can also influence the determinations of BE(ecf). IMPLICATIONS: A clinically useful way to quantify nonrespiratory disturbances of the acid-base balance is calculation of the base excess of extracellular fluid by using blood gas analyzers. In this study, we found significant variability in estimates of base excess of extracellular fluid obtained with five analyzers from different manufacturers. This variability is attributable to multiple factors, including lack of correction for deoxygenated hemoglobin (Haldane effect).     

Heparin antibodies and thromboembolism in heparin-coated and noncoated ventricular assist devices

OBJECTIVE: Coating of ventricular assist devices (VADs) with heparin improves the biocompatibility and may reduce the need for systemic anticoagulation. However, heparins are associated with the risk of formation of heparin/platelet factor 4 antibodies (HPF4/A) and the development of heparin-associated thromboemboli. We analyzed the occurrence of HPF4/A and thromboembolism in patients with heparin-coated and noncoated VADs. METHODS: One hundred patients were enrolled in the investigation. Fifty-seven received a heparin-coated (group 1) and 43 a noncoated (group 2) VAD. HPF4/A testing was performed before and 2 and 12 weeks after implantation by the heparin platelet factor 4 enzyme-linked immunosorbent assay. RESULTS: There was no significant difference in the occurrence of HPF4/A in the 2 groups (P =.102). Before the operation, 21 of the patients in group 1 had positive test responses and 25 in group 2. No patient had HPF4/A after termination of systemic heparinization. In group 1 there was no significant difference in the incidence of recurrent pump thromboses in patients who had positive test responses for HPF4/A (n = 11) when compared with those who had negative test responses (n = 9, P =.89). Twenty-one patients had HPF/A but no thromboembolism. However, all 22 patients who had thromboembolism had HPF4/A. CONCLUSIONS: Heparin coating of the VAD surface does not enhance the occurrence of HPF4/A-associated immunologic or thrombogenic reactions. However, the presence of these antibodies is strongly associated with an increased risk of thromboembolism in patients with a VAD.     

The Oxytron: a new device for administering oxygen in the spontaneously breathing patient

The Oxytron (Weinmann, Hamburg, FRG) electronic oxygen conserver (patent pending) is a new device designed to deliver precise amounts of oxygen at the optimum point in the breathing cycle via a nasal cannula. In 200 Oxytron the delivered volume of oxygen was 35 +/- 5 ml within 150-200 ms at the beginning of the inspiratory phase of the respiratory cycle. Four different settings are possible: setting 1 provides one insufflation every 4th breath; setting 2 provides one insufflation every 2nd breath; setting 3 provides three insufflations every 4 breaths; and setting 4 provides an insufflation with every breath. These settings provide approx. The equivalent of 1-4 l oxygen per minute on a continuous flow basis. Both clinical experience and literature reports show variations in savings, with an average ratio of approx. 6:1 to 7:1. In the clinical evaluation, the following advantages were found: easy handling, exact oxygen delivery, increased oxygen saving and increased oxygen delivery with increasing respiratory rate. Due to the lack of any alarm system monitoring disconnection or failure of oxygen supply must be considered a disadvantage.     

Eine faktorielle Studie von 6 Interventionen zur Vermeidung von Übelkeit und Erbrechen nach Narkosen

BACKGROUND: Untreated, one third of patients who undergo surgery will have postoperative nausea and vomiting. Although many trials have been conducted, the relative benefits of prophylactic antiemetic interventions given alone or in combination remain unknown.METHODS: In a randomized, controlled trial of factorial design, 5,199 patients at high risk for postoperative nausea and vomiting were randomly assigned to 1 of 64 possible combinations of 6 prophylactic interventions: 1) 4 mg of ondansetron or no ondansetron; 2) 4 mg of dexamethasone or no dexamethasone; 3) 1.25 mg of droperidol or no droperidol; 4) propofol or a volatile anesthetic; 5) nitrogen or nitrous oxide; 6) remifentanil or fentanyl. The primary aim parameter was nausea and vomiting within 24 h after surgery, which was evaluated blindly.RESULTS: Ondansetron, dexamethasone, and droperidol each reduced the risk of postoperative nausea and vomiting by about 26%, propofol reduced the risk by 19%, and nitrogen by 12%. The risk reduction with both of these agents (i.e., total intravenous anesthesia) was thus similar to that observed with each of the antiemetics alone. All the interventions acted independently of each other and independently of the patients' baseline risk. Consequently, the relative risks associated with the combined interventions could be estimated by multiplying the relative risks associated with each intervention. However, absolute risk reduction was a critical function of patients' baseline risk.CONCLUSIONS: Because antiemetic interventions are similarly effective and act independently, the safest or least expensive should be used first. Prophylaxis is rarely warranted in low-risk patients, moderate-risk patients may benefit from a single intervention, and multiple interventions should be reserved for high-risk patients.     

Antioxidative resuscitation solution prevents leukocyte adhesion in the liver after hemorrhagic shock.

BACKGROUND: The generation of iron-dependent toxic oxygen radicals during the initial resuscitation from hemorrhagic shock was shown to be a relevant factor for the initiation of the inflammatory cascade. Therefore, this experimental study was designed to evaluate the effects of a deferoxamine-conjugated hydroxyethyl-starch solution (HES-DFO) on oxygen radical induced injury and microcirculatory alterations in the rat liver compared with resuscitation with regular hydroxyethyl-starch, lactated Ringer's solution (RL), or a gelatin-based solution. METHODS: After hemorrhage and random assignment to 1 hour of blood-free resuscitation with the aforementioned solutions, hepatic microcirculation and leukocyte adhesion characteristics were assessed by intravital fluorescence microscopy in anesthetized rats. Oxygen radical activity was estimated by determination of glutathione levels in liver homogenate and determination of thiobarbituric acid-reactive substances in plasma as markers of lipid peroxidation. RESULTS: Resuscitation by HES-DFO resulted in restoration of hemodynamic parameters compared with gelatin-based solution and HES. The hepatic microcirculation was severely altered 1 hour after resuscitation from shock in all groups indicated by sinusoidal narrowing and reduced sinusoidal blood flow. HES-DFO, however, attenuated leukocyte adhesion and improved velocity index in sinusoids as well as sinusoidal perfusion. The shock-associated generation of oxygen radicals during resuscitation was prevented by HES-DFO as indicated by restored glutathione and reduced thiobarbituric acid-reactive substances. CONCLUSION: The results suggest that HES-DFO effectively reduces oxygen radical formation during the initial resuscitation period, thus, attenuating pathologically enhanced leukocyte adhesion and improving hepatic microcirculation.     

Accuracy of portable quantitative capnometers and capnographs under prehospital conditions

This study was designed to assess the pCO(2) accuracy of portable mainstream (Tidal Wave, Novametrix; Propaq 106, Protocol) and sidestream capnometers (Capnocheck 8200, BCI; Capnocount mini, Weinmann; NPB-75, Nellcor Puritan Bennett; SC-210, Pryon) with respect to international standards and preclinical emergency conditions. Measurements were performed under temperature conditions of +22 degrees C and -20 degrees C using dry gas mixtures with different CO(2) concentrations (STPD) and in patients ventilated with pure oxygen (BTPS). Accuracy presented to be between +1% (Capnocheck) and +12% (Propaq) (STPD) and between -0.4% (Capnocheck) and +11% (Tidal Wave) (BTPS). The measurements were affected by low ambient temperature only in the NPB-75 (+15%). Our results indicate that portable quantitative capnometers are able to fulfill accuracy requirements as requested by international standards but can be affected by changing ambient temperatures.