Prevention of Postanesthetic Shivering with Intravenous Administration of Aspirin

There have been many reports of postanesthetic shivering (PAS); however, the causes have not been defined clearly, and the reported methods of inhibiting PAS are not always available clinically. In the present study, we assessed the effect of the intravenous administration of aspirin on the prevention of PAS in 62 patients undergoing oral or maxillofacial surgery, anesthetized with enflurane-nitrous oxide. Thirty of the patients were randomly selected, and received intravenous aspirin DL-lysine 900mg (equivalent to aspirin 495mg) before the end of surgery. No significant differences were noted in the rectal temperatures between the group given aspirin and the control group. Shivering was observed in 17 of the 32 patients of control group. In contrast, shivering was observed in 5 of the 30 patients who received aspirin. This was a statistically significant difference (P < 0.01). These data indicate that intravenous administration of aspirin significantly inhibited PAS. The finding suggests that PAS is related to prostaglandin synthesis or to the formation of derivatives of arachidonic acid, since aspirin inhibits both the synthesis of prostaglandins and the formation of derivatives of arachidonic acid.(Miyawaki T, Yao H, Koyama E, et al.: Prevention of postanesthetic shivering with intravenous administration of aspirin. J Anesth 5: 123–127, 1991)     

“Haemostasis time”, a modified bleeding time test and its comparison with the duke and IVY/template bleeding times

Summary The occlusion time (haemostasis time — HT) of a thin, short cannula inserted into the cubital vein, was compared with the skin bleeding times of the Duke and Ivy/template techniques. 25 male and 25 female volunteers without a history of bleeding were divided into 5 equally large age groups ranging from 10 to over 50 years of age. They exhibited a range of 46 s–6 min 38 s (95% tolerance interval), while the Duke and Ivy/template bleeding times, which were simultaneously determined, corresponded to values given by other authors.HT is different from the skin bleeding times in that endothelium is replaced by a standard foreign surface which allows better standardization of the method. Similar results were obtained with HT compared to the skin bleeding times. These and a similar, non-significant heparin response with all three techniques suggest that HT is not more influenced by clotting factors than the Duke and Ivy/template bleeding times and, indeed, may be regarded as a bleeding time modification. HT, like both of the skin bleeding times, reflected lowered platelet counts and is even more sensitive in this respect. As tested in a group of 20 male and 20 female volunteers, HT showed a significant prolongation two hours after ingestion of 1 g aspirin. While male individuals exhibited longer bleeding times than females with the Ivy/template technique (sex-related difference p=0.01), no male to female differences were found both with HT and the Duke bleeding time.HT is easy to perform, inexpensive, leaves no scars and is safe even for the patient with severe bleeding. Moreover, compared to the skin bleeding times, it permits a differential evaluation of vessel wall and tissue effects.Dedicated to H. G. Lasch in commemoration of his 60th birthday     

缺血性卒中妇女阿司匹林抵抗的影响因素研究

目的:探讨缺血性卒中妇女阿司匹林抵抗的影响因素.方法:选取2012年1月至2015年6月收治的120例女性脑梗死患者,按是否发生阿司匹林抵抗分为司匹林抵抗(AR)组(50例)和阿司匹林敏感(AS)组(70例).统计患者临床资料,分析其与阿司匹林抵抗的关系.结果:AR组和AS组在体质量指数(BMI)、糖尿病、空腹血糖(FBG)、超敏C反应蛋白(hs-CRP)、糖化血红蛋白和血小板方面存在显著性差异(P＜0.05).Logistic回归分析显示,糖尿病、FBG、hs-CRP、糖化血红蛋白和血小板是缺血性卒中妇女阿司匹林抵抗的独立影响因素(P＜0.05).结论:糖尿病、FBG、hs-CRP、糖化血红蛋白和血小板是缺血性卒中妇女阿司匹林抵抗的独立影响因素.     

Pharmacokinetic and pharmacodynamic interactions of aspirin with warfarin in beagle dogs

1.?Warfarin and aspirin are widely used in a wide spectrum of thromboembolic and atherothrombotic diseases. Despite the potential efficacy of warfarin–aspirin therapy, the safety and side effect of combined therapy remains unclear.

2.?The aim of this study was to investigate the pharmacokinetic and pharmacodynamic interactions between warfarin and aspirin in beagles after single and multiple doses.

3.?Coadministration of aspirin had no significant effects on the area under the plasma concentration time curve (AUC_0–t) and maximum plasma concentration (C_max) of R- and S-warfarin after a single dose of warfarin, but significantly increase the AUC_0–t and C_max and dramatically decrease the clearance (CL) of R- and S-warfarin after multiple dose of warfarin. Accordingly, there was a slight increase in the AUEC_0–t and E_max of activated partial thromboplastin time (aPTT), prothrombin time (PT) and international normalized ratio (INR) after multiple dose of warfarin.

4.?Coadministration of warfarin had no markedly effects on the AUC_0–t and C_max of aspirin and its metabolite salicylic acid after single or multiple dose of aspirin. Meanwhile, the AUEC_0–t and E_max of inhibition of platelet aggregation (IPA) were not significantly affected by warfarin.

5.?Our animal study indicated that coadministration of aspirin with warfarin can cause significant pharmacokinetic and pharmacodynamic drug–drug interactions in beagles. However, more studies are urgently needed to assess related information of warfarin–aspirin drug interactions in healthy volunteers or patients.     

Determinants of aspirin resistance in patients with type 2 diabetes

BackgroundCardiovascular disease is a leading cause of mortality among patients with type 2 diabetes mellitus (T2DM). Numerous patients with T2DM show resistance to aspirin treatment, which may explain the higher rate of major adverse cardiovascular events observed compared with non-diabetes patients, and it has recently been shown that aspirin resistance is mainly related to accelerated platelet turnover with persistent high platelet reactivity (HPR) 24 h after last aspirin intake. The mechanism behind HPR is unknown. The aim of this study was to investigate the precise rate and mechanisms associated with HPR in a population of T2DM patients treated with aspirin.MethodsIncluded were 116 consecutive stable T2DM patients who had attended our hospital for their yearly check-up. HPR was assessed 24 h after aspirin intake using light transmission aggregometry (LTA) with arachidonic acid (AA) and serum thromboxane B2 (TXB2) measurement. Its relationship with diabetes status, insulin resistance, inflammatory markers and coronary artery disease (CAD) severity, using calcium scores, were investigated.ResultsUsing LTA, HPR was found in 27 (23%) patients. There was no significant difference in mean age, gender ratio or cardiovascular risk factors in patients with or without HPR. HPR was significantly related to duration of diabetes and higher fasting glucose levels (but not consistently with HbA_1c), and strongly related to all markers of insulin resistance, especially waist circumference, HOMA-IR, QUICKI and leptin. There was no association between HPR and thrombopoietin or inflammatory markers (IL-6, IL-10, indoleamine 2,3-dioxygenase activity, TNF-α, C-reactive protein), whereas HPR was associated with more severe CAD. Similar results were found with TXB2.ConclusionOur results reveal that ‘aspirin resistance’ is frequently found in T2DM, and is strongly related to insulin resistance and severity of CAD, but weakly related to HbA_1c and not at all to inflammatory parameters. This may help to identify those T2DM patients who might benefit from alternative antiplatelet treatments such as twice-daily aspirin and thienopyridines.     

Salicylate toxicity after undetectable serum salicylate concentration: a retrospective cohort study

Background: Salicylates are usually rapidly absorbed and quickly measurable in serum. An undetectable serum salicylate concentration ([ASA]) may occur early after ingestion and may be interpreted as evidence of non-exposure and not repeated. Although cases of delayed salicylate detection are reported rarely, the risk factors associated with this phenomenon are not known.

Research question: What factors are associated with an early undetectable [ASA] in salicylate poisoning?

Methods: Records from a single regional poison center were searched from 2002 to 2016 for cases of salicylate toxicity treated with bicarbonate and [ASA]?>?30?mg/dL. Cases were excluded if initial [ASA] was obtained >4?h after presentation. Case information, serial [ASA], and outcomes were recorded and compared between groups.

Results: A total of 313 records met all criteria with 11 initially undetectable [ASA] (3.5%) and 302 detectable [ASA] (96.5%). Time of first [ASA] occurred sooner in the undetectable [ASA] group (89 vs. 137?min, p?=?0.011) while time to peak [ASA] was longer (640 vs. 321?min, p?Discussion: In this series, a small but significant proportion (3.5%) of patients who developed [ASA]?>?30?mg/dL had an initially undetectable [ASA]. Those with an undetectable [ASA] were measured earlier after ingestion with a longer time to peak [ASA]. However, neither coingestion of agents prolonging gastric emptying nor reported dose ingested was different between groups. Formulation was infrequently recorded but one undetectable [ASA] did ingest a non-enteric coated product. Limitations include the small number of patients with undetectable [ASA], use of single poison center data and partial data on co-ingestants and aspirin formulation.

Conclusions: [ASA] may be undetectable early after an overdose and need for serial [ASA] in the evaluation of salicylate ingestion should be further explored. Additional research is needed to determine any causative factors and the optimal timing of [ASA] measurements.     

髋关节与膝关节人工假体置换术后阿司匹林和肝素预防深静脉血栓比较的Meta分析

目的探讨阿司匹林对比低分子肝素,对于人工髋关节、膝关节置换术后深静脉血栓形成预防的安全性及有效性。方法检索中文数据库,包括万方数据库、中国知网数据库、维普数据库、CBM数据库;英文数据库,包括Embase数据库、PubMed数据库、Cochrane Library、Web of Science,通过制订的纳入和排除标准,纳入相关文献提取数据并进行Meta分析。结果共纳入12篇文献,286233例。术后发生双下肢深静脉血栓的例数两组差异无统计学意义;阿司匹林组对比低分子肝素组:(RR=0.97,95%CI=0.78~1.19,P=0.76);术后发生肺栓塞的例数两组差异无统计学意义(RR=1.04,95%CI=0.92~1.16,P=0.55);在术后抗凝过程中出现出血相关并发症的例数两组差异无统计学意义(RR=1.05,95%CI=0.95~1.17,P=0.32);术后抗凝过程中出现因抗凝而造成的伤口并发症的例数两组差异无统计学意义(RR=1.17,95%CI=0.79~1.74,P=0.43);术后引流量两组差异无统计学意义(RR=2.76,95%CI=-92.00~97.52,P=0.95)。结论阿司匹林组对比低分子肝素组,在人工髋、膝关节置换术后深静脉血栓预防的有效性、肺栓塞预防的有效性、术后出血相关并发症、伤口并发症、引流量等方面的差异均无统计学意义,阿司匹林对于人工髋、膝关节置换术后深静脉血栓的预防有着良好的效果及安全性,可考虑将阿司匹林单独作为关节置换术后深静脉血栓形成的预防药物。