Philippe Van der Linden

Management of severe perioperative bleeding Guidelines from the European Society of Anaesthesiology

The aims of severe perioperative bleeding management are three-fold. First, preoperative identification by anamesis and laboratory testing of those patients for whom the perioperative bleeding risk may be increased. Second, implementation of strategies for correcting preoperative anaemia and stabilisation of the macro- and microcirculations in order to optimise the patients tolerance to bleeding. Third, targeted procoagulant interventions to reduce the amount of bleeding, morbidity, mortality and costs. The purpose of these guidelines is to provide an overview of current knowledge on the subject with an assessment of the quality of the evidence in order to allow anaesthetists throughout Europe to integrate this knowledge into daily patient care wherever possible. The Guidelines Committee of the European Society of Anaesthesiology (ESA) formed a task force with members of scientific subcommittees and individual expert members of the ESA. Electronic databases were searched without language restrictions from the year 2000 until 2012. These searches produced 20 664 abstracts. Relevant systematic reviews with meta-analyses, randomised controlled trials, cohort studies, case-control studies and cross-sectional surveys were selected. At the suggestion of the ESA Guideline Committee, the Scottish Intercollegiate Guidelines Network (SIGN) grading system was initially used to assess the level of evidence and to grade recommendations. During the process of guideline development, the official position of the ESA changed to favour the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. This report includes general recommendations as well as specific recommendations in various fields of surgical interventions. The final draft guideline was posted on the ESA website for four weeks and the link was sent to all ESA members. Comments were collated and the guidelines amended as appropriate. When the final draft was complete, the Guidelines Committee and ESA Board ratified the guidelines.

Cardioprotective properties of sevoflurane in patients undergoing coronary surgery with cardiopulmonary bypass are related to the modalities of its administration

Background:Experimental studies have related the cardioprotective effects of sevoflurane both to preconditioning properties and to beneficial effects during reperfusion. In clinical studies, the cardioprotective effects of volatile agents seem more important when administered throughout the procedure than when used only in the preconditioning period. The authors hypothesized that the cardioprotective effects of sevoflurane observed in patients undergoing coronary surgery with cardiopulmonary bypass are related to timing and duration of its administration. Methods:Elective coronary surgery patients were randomly assigned to four different anesthetic protocols (n = 50 each). In a first group, patients received a propofol based intravenous regimen (propofol group). In a second group, propofol was replaced by sevoflurane from sternotomy until the start of cardiopulmonary bypass (SEVO pre group). In a third group, propofol was replaced by sevoflurane after completion of the coronary anastomoses (SEVO post group). In a fourth group, propofol was administered until sternotomy and then replaced by sevoflurane for the remaining of the operation (SEVO all group). Postoperative concentrations of cardiac troponin I were followed during 48 h. Cardiac function was assessed perioperatively and during 24 h postoperatively. Results:Postoperative troponin I concentrations in the SEVO all group were lower than in the propofol group. Stroke volume decreased transiently after cardiopulmonary bypass in the propofol group but remained unchanged throughout in the SEVO all group. In the SEVO pre and SEVO post groups, stroke volume also decreased after cardiopulmonary bypass but returned earlier to baseline values than in the propofol group. Duration of stay in the intensive care unit was lower in the SEVO all group than in the propofol group. Conclusion:In patients undergoing coronary artery surgery with cardiopulmonary bypass, the cardioprotective effects of sevoflurane were clinically most apparent when it was administered throughout the operation.

Effects of Propofol, Desflurane, and Sevoflurane on Recovery of Myocardial Function after Coronary Surgery in Elderly High-risk Patients

Background The present study investigated the effects of propofol, desflurane, and sevoflurane on recovery of myocardial function in high-risk coronary surgery patients. High-risk patients were defined as those older than 70 yr with three-vessel disease and an ejection fraction less than 50% with impaired length-dependent regulation of myocardial function. Methods Coronary surgery patients (n = 45) were randomly assigned to receive either target-controlled infusion of propofol or inhalational anesthesia with desflurane or sevoflurane. Cardiac function was assessed perioperatively and during 24 h postoperatively using a Swan-Ganz catheter. Perioperatively, a high-fidelity pressure catheter was positioned in the left and right atrium and ventricle. Response to increased cardiac load, obtained by leg elevation, was assessed before and after cardiopulmonary bypass (CPB). Effects on contraction were evaluated by analysis of changes in dP/dtmax. Effects on relaxation were assessed by analysis of the load-dependence of myocardial relaxation. Postoperative levels of cardiac troponin I were followed for 36 h. Results After CPB, cardiac index and dP/dtmax were significantly lower in patients under propofol anesthesia. Post-CPB, leg elevation resulted in a significantly greater decrease in dP/dtmax in the propofol group, whereas the responses in the desflurane and sevoflurane groups were comparable with the responses before CPB. After CPB, load dependence of left ventricular pressure drop was significantly higher in the propofol group than in the desflurane and sevoflurane group. Troponin I levels were significantly higher in the propofol group. Conclusions Sevoflurane and desflurane but not propofol preserved left ventricular function after CPB in high-risk coronary surgery patients with less evidence of myocardial damage postoperatively.

Choice of Primary Anesthetic Regimen Can Influence Intensive Care Unit Length of Stay after Coronary Surgery with Cardiopulmonary Bypass

Background:Volatile anesthetics protect the myocardium during coronary surgery. This study hypothesized that the use of a volatile agent in the anesthetic regimen would be associated with a shorter intensive care unit (ICU) and hospital length of stay (LOS), compared with a total intravenous anesthetic regimen. Methods:Elective coronary surgery patients were randomly assigned to receive propofol (n = 80), midazolam (n = 80), sevoflurane (n = 80), or desflurane (n = 80) as part of a remifentanil-based anesthetic regimen. Multiple logistic regression analysis was used to identify the independent variables associated with a prolonged ICU LOS. Results:Patient characteristics were similar in all groups. ICU and hospital LOS were lower in the sevoflurane and desflurane groups (P < 0.01). The number of patients who needed a prolonged ICU stay (> 48 h) was also significantly lower (propofol: n = 31; midazolam: n = 34; sevoflurane: n = 10; desflurane: n = 15; P < 0.01). Occurrence of atrial fibrillation, a postoperative troponin I concentration greater than 4 ng/ml, and the need for prolonged inotropic support (> 12 h) were identified as the significant risk factors for prolonged ICU LOS. Postoperative troponin I concentrations and need for prolonged inotropic support were lower in the sevoflurane and desflurane group (P < 0.01). Postoperative cardiac function was also better preserved with the volatile anesthetics. The incidence of other postoperative complications was similar in all groups. Conclusions:The use of sevoflurane and desflurane resulted in a shorter ICU and hospital LOS. This seemed to be related to a better preservation of early postoperative myocardial function.

Safety of Modern Starches Used During Surgery

Various hydroxyethyl starch (HES) preparations have been used for decades to augment blood volume. There has been concern recently regarding possible adverse outcomes when using HES in the intensive care setting, especially in patients with septic shock. However, the pharmacokinetic and pharmacodynamic properties of HES preparations depend on their chemical composition and source material. Thus, different clinical conditions could result in differing effectiveness and safety for these preparations. Consequently, we assessed the safety of tetrastarches when used during surgery, using a formal search, that yielded 59 primary full publications of studies that met a priori inclusion criteria and randomly allocated 4529 patients with 2139 patients treated with tetrastarch compared with 2390 patients treated with a comparator. There were no indications that the use of tetrastarches during surgery induces adverse renal effects as assessed by change or absolute concentrations of serum creatinine or need for renal replacement therapy (39 trials, 3389 patients), increased blood loss (38 trials, 3280 patients), allogeneic erythrocyte transfusion (20 trials, 2151 patients; odds ratio for HES transfusion 0.73 [95% confidence interval = 0.61–0.87], P = 0.0005), or increased mortality (odds ratio for HES mortality = 0.51 [0.24–1.05], P = 0.079).

Surgery and invasive procedures in patients on long-term treatment with direct oral anticoagulants: thrombin or factor-Xa inhibitors. Recommendations of the Working Group on Perioperative Haemostasis and the French Study Group on Thrombosis and Haemostasis.

Direct oral anticoagulants (DOAs)--inhibitors of thrombin or factor-Xa--are expected to replace vitamin K antagonists in most of their indications. Patients receiving long-term treatment with DOAs are likely to be exposed to elective or emergency surgery or invasive procedures. Owing to the present lack of experience in such conditions, we cannot make recommendations, but only propose perioperative management for optimal safety regarding the risk of bleeding and thrombosis. DOAs may increase surgical bleeding, they have no validated antagonists, they cannot be monitored by simple standardized laboratory assays and their pharmacokinetics vary significantly between patients. Although DOAs differ in many respects, the proposals in the perioperative setting need not be specific to each. For procedures with low haemorrhagic risk, a therapeutic window of 48 hours (last administration 24 hours before surgery, restart 24 hours after) is proposed. For procedures with medium or high haemorrhagic risk, we suggest stopping DOAs 5 days before surgery to ensure complete elimination in all patients. Treatment should be resumed only when the risk of bleeding has been controlled. In patients at high thrombotic risk (e.g. those in atrial fibrillation with a history of stroke), bridging with heparin (low molecular-weight heparin, or unfractionated heparin, if the former is contraindicated) is proposed. In an emergency, the procedure should be postponed for as long as possible (minimum 1-2 half-lives) and non-specific antihaemorrhagic agents, such as recombinant human activated factor VIIa or prothrombin complex concentrates should not be given for prophylactic reversal due to their uncertain benefit-risk.

The effects of hydroxyethyl starch 130/0.4 (6%) on blood loss and use of blood products in major surgery: a pooled analysis of randomized clinical trials.

BACKGROUND: The effects of different types of hydroxylethyl starch (HES) on blood coagulation closely depend on their physicochemical properties. HES with lower molar substitution and a lower in vivo molecular weight interferes relatively little with hemostasis and therefore results in lower perioperative blood losses and red blood cell (RBC) transfusion. To test this hypothesis, we analyzed pooled data from all available studies in major surgery comparing 6% HES 130/0.4 and 6% HES 200/0.5 from waxy maize starch. METHODS: Estimated blood loss, drainage loss, calculated blood loss, transfused blood product volumes, and coagulation variables were examined for 24 h after the start of surgery. Groups were compared using analysis of variance, evaluating several covariates. RESULTS: Four-hundred-forty-nine patients from seven clinical trials were analyzed, 228 received HES 130/0.4, and 221 received HES 200/0.5. For HES 130/0.4 patients, when compared to HES 200/0.5 patients, the estimated blood loss was reduced by 404 mL [P = 0.006], drainage loss was 272 mL less [P = 0.009], and calculated RBC loss was 149 mL less [P = 0.003]. RBC transfusion volumes were also lower for HES 130/0.4 by 137 mL [P = 0.004]. In the early postoperative phase, HES 130/0.4 was found to exert significantly less effect on measures of coagulation, especially activated partial thromboplastin time and von Willebrand factor (antigen and ristocetin cofactor), than HES 200/0.5. CONCLUSIONS: Blood loss and transfusion requirements can be significantly reduced in major surgery when using third generation HES 130/0.4 (Voluven®) compared to second generation waxy maize starch HES 200/0.5. Since HES 130/0.4 and HES 200/0.5 were found similar regarding volume efficacy in other studies, HES 130/0.4 is recommended in this clinical setting.

The effects of levosimendan in cardiac surgery patients with poor left ventricular function.

BACKGROUND:Patients with poor left ventricular function often require inotropic drug support immediately after cardiopulmonary bypass. Levosimendan improves cardiac function by a novel mechanism of action compared to currently available drugs. We hypothesized that, in patients with severely compromised ventricular function, the use of levosimendan would be associated with better postoperative cardiac function than with inotropic drugs that increase myocardial oxygen consumption. METHODS:Thirty patients with a preoperative ejection fraction ≤30% scheduled for elective cardiac surgery with cardiopulmonary bypass were randomized to two different inotropic protocols: milrinone 0.5 mg · kg−1 · min−1 or levosimendan 0.1 mg · kg−1 · min−1, started immediately after the release of the aortic crossclamp. The treatment was masked to the observers. All patients received dobutamine 5 mg · kg−1 · min−1. RESULTS:Stroke volume was similar between groups initially after surgery, but it declined 12 h after surgery in the milrinone group but not in the levosimendan group (P < 0.05 between groups) despite similar filling pressures. Total dose, duration of inotropic drug administration and norepinephrine dose were lower in the levosimendan group than in the milrinone group (P < 0.05). The duration of tracheal intubation was shorter in the former group compared with the milrinone group (P = 0008). Three patients in the milrinone group but none in the levosimendan group died within 30 days of surgery. CONCLUSION:In cardiac surgery patients with a low preoperative ejection fraction, stroke volume was better maintained with the combination of dobutamine with levosimendan than with the combination of dobutamine with milrinone.

Cardiovascular and metabolic response to acute normovolemic anemia. Effects of anesthesia.

BackgroundThe maintenance of adequate tissue oxygenation during acute anemia depends on an increase in both cardiac output and tissue oxygen extraction. This study tested the hypothesis that anesthesia blunts the cardiac output response associated with acute normovolemic hemodilution. MethodsForty patients undergoing major abdominal surgery were prospectively randomized to undergo acute normovolemic hemodilution (ANH) either awake (awake group, n = 20) or with fentanyl–nitrous oxide–isoflurane anesthesia (anesthetized group, n = 20). Radial and pulmonary artery catheters were placed in all patients. After hemodynamic measurements were taken, patients in the two groups underwent hemodilution to decrease their hemoglobin concentration from 13 to 8 g/dl. A total of 1,875 ± 222 ml (mean ± SD) of blood was collected and simultaneously replaced by the same volume of medium molecular weight hydroxyethylstarch in both groups. ResultsIn the awake group, ANH resulted in a significant increase in cardiac index (from 3.1 ± 0.5 to 4.8 ± 1.0 l · min−1 · m−2) related to both an increase in heart rate and stroke index. Oxygen delivery remained unchanged, but oxygen consumption increased significantly, resulting in an increase in oxygen extraction ratio. In the anesthetized group, ANH resulted in a significantly smaller increase in cardiac index (from 2.3 ± 0.5 to 3.1 ± 0.7 l · min−1 · m−2) related solely to an increase in stroke index. Oxygen delivery decreased but oxygen consumption was maintained as oxygen extraction increased. ConclusionsAnesthesia significantly reduces the cardiac output response associated with ANH. This could be related to the effects of the anesthetic drugs on the autonomic and the cardiovascular systems.

Hydroxyethyl starch 130/0.4 versus modified fluid gelatin for volume expansion in cardiac surgery patients: The effects on perioperative bleeding and transfusion needs

In this prospective, randomized, open controlled study we compared the effects on net red blood cell loss of 6% hydroxyethyl starch 130/0.4 (HES: n = 64) and 3% modified fluid gelatin (GEL: n = 68) administered for intravascular volume management in patients undergoing coronary surgery. Blood losses were calculated from determination of circulating blood volume and measurement of preoperative and postoperative hematocrit. Amount of colloids that could be administered was limited to 50 mL/kg. If additional fluids were required, balanced crystalloid solution was used. Anesthetic and surgical techniques were standardized. Both groups were similar with regard to demographic and intraoperative variables. Total study drug was 48.9 ± 17.2 mL/kg in the HES group and 48.9 ± 14.6 mL/kg in the GEL group. Total red blood cell loss was 544 ± 305 mL in the HES group and 504 ± 327 mL the GEL group. Measured blood losses were also similar in both groups (HES, 19.4 ± 12.3 mL/kg; GEL, 19.2 ± 14.5 mL/kg). Exposure to allogeneic blood product was comparable in both groups. In the conditions of the present study, HES 130/0.4 up to 50 mL/kg is a valuable alternative to modified fluid gelatin for plasma volume expansion during and after cardiac surgery.