Updates in perioperative coagulation: physiology and management of thromboembolism and haemorrhage

Understanding of blood coagulation has evolved significantly in recent years. Both new coagulation proteins and inhibitors have been found and new interactions among previously known components of the coagulation system have been discovered. This increased knowledge has led to the development of various new diagnostic coagulation tests and promising antithrombotic and haemostatic drugs. Several such agents are currently being introduced into clinical medicine for both the treatment or prophylaxis of thromboembolic disease and for the treatment of bleeding. This review aims to elucidate these new concepts and to outline some consequences for clinical anaesthesia and perioperative medicine

Prämedikationsqualität und Patientenzufriedenheit nach Prämedikation mit Midazolam, Clonidin oder Placebo: Randomisierte Doppelblindstudie mit altersangepasster Dosierung

Zusammenfassung: Hintergrund: Die Prämedikation hat u.a. zum Ziel, Angstgefühle und innere Unruhe vor einem chirurgischen Eingriff zu lindern und gleichzeitig möglichst wenig unerwünschte Wirkungen zu verursachen. Es gibt bisher keine Untersuchungen, die die Wirkungen und Nebenwirkungen von Clonidin (Catapresan®), Midazolam (Dormicum®) und Placebo in altersabhängig unterschiedlicher Dosierung verglichen und deren Akzeptanz beim Patienten untersucht haben. Patienten und Methoden: In dieser randomisierten, placebokontrollierten Studie wurden 139 erwachsene Patienten untersucht und 60min vor der Narkoseeinleitung mit Clonidin, Midazolam oder Placebo prämediziert. Angst, Sedierungstiefe und Nebenwirkungen wurden an 6 aufeinanderfolgenden Zeitpunkten erfasst. Ergebnisse: Midazolam zeigte eine stärkere anxiolytische und sedative Wirkung als Clonidin. Die Prämedikation mit Midazolam verminderte die Sauerstoffsättigung. Es gab keine klinisch relevanten Veränderungen in der Hämodynamik in allen Gruppen. Midazolam und Clonidin verminderten das Risiko für "postoperative nausea and vomiting" (PONV). Midazolam zeigte die geringsten Nebenwirkungen. Placebo wurde von den Patienten weitaus am schlechtesten beurteilt, im Gegensatz zu Clonidin und Midazolam, das am besten beurteilt wurde. Schlussfolgerung: Die sedierende und anxiolytische Wirkung von Midazolam ist stärker als diejenige von Clonidin. Midazolam wurde von den Patienten besser angenommen als Clonidin, Clonidin siginfikant besser als Placebo. Die meisten Patienten würden Midazolam wieder wähle

Allogeneic red blood cell transfusions: efficacy, risks, alternatives and indications

Careful assessment of risks and benefits has to precede each decision on allogeneic red blood cell (RBC) transfusion. Currently, a number of key issues in transfusion medicine are highly controversial, most importantly the influence of different transfusion thresholds on clinical outcome. The aim of this article is to review current evidence on blood transfusions, to highlight 'hot topics' with respect to efficacy, outcome and risks, and to provide the reader with transfusion guidelines. In addition, a brief synopsis of transfusion alternatives will be given. Based on up-to-date information of current evidence, together with clinical knowledge and experience, the physician will be able to make transfusion decisions that bear the lowest risk for the patient

Coagulopathy and blood component transfusion in trauma

Trauma is a serious global health problem, accounting for approximately one in 10 deaths worldwide. Uncontrollable bleeding accounts for 39% of trauma-related deaths and is the leading cause of potentially preventable death in patients with major trauma. While bleeding from vascular injury can usually be repaired surgically, coagulopathy-related bleeding is often more difficult to manage and may also mask the site of vascular injury. The causes of coagulopathy in patients with severe trauma are multifactorial, including consumption and dilution of platelets and coagulation factors, as well as dysfunction of platelets and the coagulation system. The interplay between hypothermia, acidosis and progressive coagulopathy, referred to as the 'lethal triad', often results in exsanguination. Current management of coagulopathy-related bleeding is based on blood component replacement therapy. However, there is a limit on the level of haemostasis that can be restored by replacement therapy. In addition, there is evidence that transfusion of red blood cells immediately after injury increases the incidence of post-injury infection and multiple organ failure. Strategies to prevent significant coagulopathy and to control critical bleeding effectively in the presence of coagulopathy may decrease the requirement for blood transfusion, thereby improving clinical outcome of patients with major trauma

Allogeneic blood transfusions: benefit, risks and clinical indications in countries with a low or high human development index.

The risks associated with allogeneic red blood cell (RBC) transfusions differ significantly between countries with low and high human development indexes (HDIs). In countries with a low HDI, the risk of infection (HIV, HBV, HCV and malaria) is elevated. In contrast, in countries with a high HDI, immunological reactions (haemolytic transfusion reactions, alloimmunization and immunosuppression) are predominant. Therefore the overall risk associated with RBC transfusions in low HDI countries is much more significant than that in high HDI countries. In view of these risks, the limited efficacy of RBC transfusion and its high costs, this procedure should be used sparingly and rationally. Therefore RBC transfusion protocols adapted to the local situation are essential. Such protocols should distinguish between physiological and haemoglobin-based transfusion triggers. In countries with a high HDI, relative tachycardia and hypotension, despite normovolaemia, ST-segment changes suggestive of myocardial ischaemia and an Hb level <6 g/dl can serve as general guidelines for transfusion. Higher haemoglobin transfusion triggers should be used for patients aged >80 years and those with coronary artery or cerebrovascular disease. In countries with a low HDI, clinical signs of circulatory failure or myocardial ischaemia and an Hb level <5 g/dl can serve as transfusion guidelines

Preconditioning with sevoflurane decreases PECAM-1 expression and improves one-year cardiovascular outcome in coronary artery bypass graft surgery

BACKGROUND: Cardiac preconditioning is thought to be involved in the observed decreased coronary artery reocclusion rate in patients with angina preceding myocardial infarction. We prospectively examined whether preconditioning by sevoflurane would decrease late cardiac events in patients undergoing coronary artery bypass graft (CABG) surgery. METHODS: Seventy-two patients scheduled for elective CABG surgery were randomized to preconditioning by sevoflurane (10 min at 4 vol%) or placebo. For all patients, follow-up of adverse cardiac events was obtained 6 and 12 months after surgery. Transcript levels for platelet-endothelial cell adhesion molecule-1 (PECAM-1/CD31), catalase and heat shock protein 70 (Hsp70) were determined in atrial biopsies after sevoflurane preconditioning. RESULTS: Pharmacological preconditioning by sevoflurane reduced the incidence of late cardiac events during the first year after CABG surgery (sevoflurane 3% vs 17% in the placebo group, log-rank test, P=0.038). One patient in the sevoflurane group and three patients in the placebo group experienced new episodes of congestive heart failure and three additional patients had coronary artery reocclusion. Perioperative peak concentrations for myocardial injury markers were higher in patients with subsequent late cardiac events [NTproBNP, 9031 (4125) vs 3049 (1906) ng litre(-1), P<0.001; cTnT, 1.31 (0.88) vs 0.46 (0.29) microg litre(-1), P<0.001]. Transcript levels were reduced for PECAM-1 and increased for catalase but unchanged for Hsp70 in atrial biopsies after sevoflurane preconditioning. CONCLUSIONS: This prospective randomized clinical study provides evidence of a protective role for pharmacological preconditioning by sevoflurane in late cardiac events in CABG patients, which may be related to favourable transcriptional changes in pro- and antiprotective proteins

Molar substitution and C2/C6 ratio of hydroxyethyl starch: influence on blood coagulation

BACKGROUND: Development of hydroxyethyl starches (HES) with a low impact on blood coagulation but a long intravascular persistence is of clinical interest. A previous in vitro study showed that low substituted high molecular weight HES does not compromise blood coagulation more than medium molecular weight HES. In the present study we assessed the individual effects on blood coagulation of molar substitution and C2/C6 ratio of a high molecular weight HES. METHODS: Blood was obtained from 30 healthy patients undergoing elective surgery and mixed with six high molecular weight (700 kDa) HES solutions differing in their molar substitution (0.42 and 0.51) and C2/C6 ratio (2.7, 7 and 14) to achieve 20, 40 and 60% dilution. Blood coagulation was assessed by Thrombelastograph analysis (TEG) and plasma coagulation tests. Data were compared using a three-way analysis of variance model with repeated measures on the three factors. RESULTS: Higher molar substitution compromised blood coagulation most (for all TEG parameters, P<0.05). The lowest C2/C6 ratio was associated with the lowest effect on blood coagulation; r (P<0.001), angle alpha (P=0.003) and coagulation index (P<0.001). No effect on k and maximum amplitude was observed (P for both >0.50). The higher molar substitution was associated with a lesser increase in PT (P=0.007) and a greater decrease in factor VIII (P=0.010). PTT, functional and antigenic von Willebrand factors were not significantly influenced by molar substitution (P for all >0.20). No significant differences between solutions with the same molar substitution but different C2/C6 ratios were found in plasma coagulation parameters (P for all >0.05). CONCLUSIONS: TEG analysis indicates that high molecular HES with a molar substitution of 0.42 and a C2/C6 ratio of 2.7 has the lowest effect on in vitro human blood coagulation

Patient well-being after general anaesthesia: a prospective, randomized, controlled multi-centre trial comparing intravenous and inhalation anaesthesia

Background. The aim of this study was to assess postoperative patient well‐being after total i.v. anaesthesia compared with inhalation anaesthesia by means of validated psychometric tests. Methods. With ethics committee approval, 305 patients undergoing minor elective gynaecologic or orthopaedic interventions were assigned randomly to total i.v. anaesthesia using propofol or inhalation anaesthesia using sevoflurane. The primary outcome measurement was the actual mental state 90 min and 24 h after anaesthesia assessed by a blinded observer using the Adjective Mood Scale (AMS) and the State‐Trait‐Anxiety Inventory (STAI). Incidence of postoperative nausea and vomiting (PONV) and postoperative pain level were determined by Visual Analogue Scale (VAS) 90 min and 24 h after anaesthesia (secondary outcome measurements). Patient satisfaction was evaluated using a VAS 24 h after anaesthesia. Results. The AMS and STAI scores were significantly better 90 min after total i.v. anaesthesia compared with inhalation anaesthesia (P=0.02, P=0.05, respectively), but equal 24 h after both anaesthetic techniques (P=0.90, P=0.78, respectively); patient satisfaction was comparable (P=0.26). Postoperative pain was comparable in both groups 90 min and 24 h after anaesthesia (P=0.11, P=0.12, respectively). The incidence of postoperative nausea was reduced after total i.v. compared with inhalation anaesthesia at 90 min (7 vs 35%, P<0.001), and 24 h (33 vs 52%, P=0.001). Conclusion. Total i.v. anaesthesia improves early postoperative patient well‐being and reduces the incidence of PONV. Br J Anaesth 2003; 91: 631-