International Journal of
HEMATOLOGY
The Effects of Desflurane on Human Platelet Aggregation In Vitro Hülya Türkan,a Cengiz Beyan,b Lale Karabıyık,c Derya Güner,d Kürs¸at Kaptanb a
Clinic of Anaesthesiology, Department of Emergency Medicine, and bDepartment of Haematology, Gulhane Military Medical Academy; cDepartment of Anaesthesiology, Gazi University, Faculty of Medicine; d Department of Anaesthesiology, Ministry of Health Ankara Training and Research Hospital, Ankara, Turkey Received May 5, 2003; received in revised form February 4, 2004; accepted March 29, 2004
Abstract In view of the possible antiplatelet effects of general anesthetics, we investigated the in vitro effects of desflurane, a new inhalation agent, on platelet aggregation. For 15 patients who underwent elective operations, blood was sampled with desflurane induction before and after anesthesia but prior to surgery so that platelet aggregation in the drawn blood could be tested before desflurane anesthesia and again after exposure to the anesthetic. Platelet aggregation was measured with a whole-blood aggregometer. Adenosine diphosphate (ADP), collagen, and ristocetin were used as aggregating agents. Our results showed that aggregation in response to ADP, collagen, or ristocetin was not inhibited in patients who received desflurane anesthesia. This study with an in vitro model showed that desflurane had no influence on platelets in clinically relevant doses. Int J Hematol. 2004;80:91-93. doi: 10.1532/IJH97.E0309 ©2004 The Japanese Society of Hematology Key words: Anesthetics; Desflurane; Platelet aggregation; Platelet function
1. Introduction
2. Materials and Methods
Because platelets play an important role in hemostasis during surgery, the effect of anesthetic agents on platelets is an important clinical issue [1]. Platelet aggregation tests are specific and sensitive for platelet function. The effects of several inhalation anesthetic agents, such as halothane, enflurane, isoflurane, and sevoflurane, have been studied, but desflurane, which is the newest inhalation agent, has not. Desflurane, which has recently been introduced into clinical use, has many advantages over the other inhalation anesthetics, including a rapid onset and short duration of anesthesia and the absence of inhibitory cardiac side effects, and therefore has become widely used for general anesthesia [2]. It is more resistant than any of the other presently available halogenated anesthetics, making the possibility of hepatic or renal toxicity remote [3]. In this study, we investigated the hematologic effect of desflurane by examining changes in platelet aggregation during general anesthesia with desflurane.
After approval from the institutional ethics committee and informed written consent were obtained, 15 patients were included for the study. The mean age (SD) of the enrolled patients (8 women, 7 men) was 38.4 10.7 years. The mean patient weight was 64.4 9 kg, and the mean height was 171.8 2 cm. Thirteen patients were in American Society of Anesthesiology (ASA) class I, and 2 patients were in ASA class II. None of the patients had endocrine, renal, or systemic inflammatory diseases or any malignant process. There was no history of coagulopathy in any patient, and no patient had taken any prophylaxis for thromboembolic disease or any other medication that affects platelet aggregation for at least 2 weeks prior to surgery. Patients were selected on the basis of a hematocrit level between 38% and 45% and a normal platelet count between 150 103/mL and 350 103/mL. The type of surgery was not important because we completed the study before the surgery started. All studies were done in the morning after the patients had fasted overnight. No presurgery medication was given. The electrocardiogram, pulse oximeter, arterial blood pressure, temperature, end-tidal carbon dioxide level, and desflurane concentrations were monitored continuously (AS/3 and CS/3 physiological monitoring systems; Datex-Ohmeda, Helsinki, Finland). Heart rate and blood pressure were within 10% of preoperative limits during the study period. Oxygen saturation, end-tidal carbon dioxide levels, and temperature values also did not change. After control blood samples were
Presented at the 29th World Congress of the International Society of Hematology, Seoul, Korea, August 24-28, 2002. Correspondence and reprint requests: Cengiz Beyan, Prof, MD, Gulhane Military Medical Academy, Director of Haematology, 06010 Etlik, Ankara, Turkey; 90-312-304-41-01; fax: 90-312-304-2010 (e-mail:
[email protected]).
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taken, all patients received 1 g/kg remifentanil (Ultiva; GlaxoSmithKline, Research Triangle Park, NC, USA) intravenously and started to inhale 7% to 10% desflurane (Suprane; Baxter, Chicago, IL, USA) in 4 L/min of oxygen with the anesthesia machine (S/5 physiological monitoring system; Datex-Ohmeda). To avoid stress responses, we did not perform any laryngoscopy or endotracheal intubation. The patients were breathing spontaneously by mask, and surgery was not started during this period to avoid the effects of surgical stress. In addition, patients who coughed or held their breath were excluded from the study. No other drugs or fluids that could possibly affect platelet aggregation were administered during that interval. Second venous blood samples were drawn from the antecubital vein without a tourniquet and with a 20-gauge needle after the bispectral index (A-2000 BIS monitor; Aspect Medical Systems, Newton, MA, USA) was 50 5 after approximately 20 minutes of inhalation of desflurane in oxygen. These samples were treated with 3.8% sodium citrate anticoagulant solution (blood-anticoagulant ratio, 9:1). There was no hemolysis in the samples. They were kept at room temperature and tested within 60 minutes of collection. To ensure against loss of desflurane from the samples, we used sealed containers during the platelet isolation procedures and monitored desflurane concentrations in final platelet samples by gas chromatography. Platelets were counted in an automated cell counter device (Cell-Dyn 1700; Abbott Laboratories, Abbott Park, IL, USA). Platelet aggregation was induced by 5 M adenosine diphosphate (ADP), 0.2 mg/mL collagen, or 1.2 mg/mL ristocetin. The analyses were performed by using a Whole Blood Lumi-Aggregometer (Model 560-Ca; Chrono-log Corporation, Havertown, PA, USA) according to a SigmaAldrich diagnostics protocol (procedure no. 885; SigmaAldrich, St. Louis, MO, USA). Platelet aggregation was performed by using Sigma-Aldrich platelet-aggregating reagents (code no. 885/A; 885/3 for ADP, 885/1 for collagen, and 885/7 for ristocetin). Blood samples were centrifuged (250g, 10 minutes) to isolate platelet-rich plasma in the supernatant. The remainder of the blood was centrifuged again (1500g, 10 minutes) to prepare platelet-poor plasma, as has previously been described [4]. The platelet-rich plasma was diluted with the platelet-poor plasma to yield test samples of platelet-rich plasma with a final count of 250,000 50,000/mL. Dose-response curves were calculated automatically by the device and evaluated for amplitude and slope. Statistical analysis was done with the Wilcoxon matchedpairs signed rank test. P values .05 >.05 >.05 >.05 >.05 >.05
Effect of Desflurane on Platelet Aggregation
tion. Our results suggest that desflurane can be used in patients at increased risk of intraoperative and postoperative hemorrhage. However, we cannot rule out platelet dysfunction in these patients because in vitro platelet aggregation tests do not reflect in vivo platelet function.
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