NOACs in Anesthesiology.

BACKGROUND: Due to increasing use of new oral anticoagulants (NOACs), clinicians are faced more and more frequently with clinical issues related to these drugs. OBJECTIVE: The objective of this publication is to make practical suggestions for the perioperative management of NOACs as well as for their handling in overdoses and bleedings. RECOMMENDATIONS: In elective surgery and creatinine clearance ≥ 50 ml/min, a NOAC should be discontinued 24-36 h before the intervention, and even earlier in case of reduced kidney function. In emergency interventions that cannot be delayed, the management is dependent on the NOAC plasma levels. With levels ≤ 30 ng/ml, surgery can be performed. With levels >30 ng/ml, reversal agents should be considered. In low bleeding risk surgery, NOACs can be re-started 24 h after the intervention, which is prolonged to 48-72 h after surgery with high bleeding risk. In case of NOAC overdose and minor bleedings, temporary discontinuation and supportive care are usually sufficient to control the situation. In severe or life-threatening bleedings, nonspecific and specific reversal agents should be considered.

Is our heart a well-designed pump? The heart along animal evolution.

A carrier system for gases and nutrients became mandatory when primitive animals grew larger and developed different organs. The first circulatory systems are peristaltic tubes pushing slowly the haemolymph into an open vascular tree without capillaries (worms). Arthropods developed contractile bulges on the abdominal aorta assisted by accessory hearts for wings or legs and by abdominal respiratory motions. Two-chamber heart (atrium and ventricle) appeared among mollusks. Vertebrates have a multi-chamber heart and a closed circulation with capillaries. Their heart has two chambers in fishes, three chambers (two atria and one ventricle) in amphibians and reptiles, and four chambers in birds and mammals. The ventricle of reptiles is partially divided in two cavities by an interventricular septum, leaving only a communication of variable size leading to a variable shunt. Blood pressure increases progressively from 15 mmHg (worms) to 170/70 mmHg (birds) according to the increase in metabolic rate. When systemic pressure exceeds 50 mmHg, a lower pressure system appears for the circulation through gills or lungs in order to improve gas exchange. A four-chamber heart allows a complete separation of systemic and pulmonary circuits. This review describes the circulatory pumping systems used in the different classes of animals, their advantages and failures, and the way they have been modified with evolution.

Perioperative antiplatelet therapy.

Aspirin is recommended as a lifelong therapy that should never be interrupted for patients with cardiovascular dis- ease. Clopidogrel therapy is mandatory for six weeks after placement of bare-metal stents, three to six months after myocardial infarction, and at least 12 months after placement of drug-eluting stents. Because of the hypercoagulable state induced by surgery, early withdrawal of antiplatelet therapy for secondary prevention of cardiovascular disease increases the risk of postoperative myocardial infarction and death five- to 10-fold in stented patients who are on continuous dual antiplatelet therapy. The shorter the time between revascularization and surgery, the higher the risk of adverse cardiac events. Elective surgery should be postponed beyond these periods, whereas vital, semiurgent, or urgent operations should be performed under continued dual antiplatelet therapy. The risk of surgical hemorrhage is increased approximately 20 percent by aspirin or clopidogrel alone, and 50 percent by dual antiplatelet therapy. The present clinical data suggest that the risk of a cardiovascular event when stopping antiplatelet agents preoperatively is higher than the risk of surgical bleeding when continuing these drugs, except during surgery in a closed space (e.g., intracranial, posterior eye chamber) or surgeries associated with massive bleeding and difficult hemostasis.

Urological surgery and antiplatelet drugs after cardiac and cerebrovascular accidents.

PURPOSE: The perioperative treatment of patients on dual antiplatelet therapy after myocardial infarction, cerebrovascular event or coronary stent implantation represents an increasingly frequent issue for urologists and anesthesiologists. We assess the current scientific evidence and propose strategies concerning treatment of these patients. MATERIALS AND METHODS: A MEDLINE and PubMed search was conducted for articles related to antiplatelet therapy after myocardial infarction, coronary stents and cerebrovascular events, as well as the use of aspirin and/or clopidogrel in the context of surgery. RESULTS: Early discontinuation of antiplatelet therapy for secondary prevention is associated with a high risk of coronary thrombosis, which is further increased by the hypercoagulable state induced by surgery. Aspirin has recently been recommended as a lifelong therapy. Clopidogrel is mandatory for 6 weeks after myocardial infarction and bare metal stents, and for 12 months after drug-eluting stents. Surgery must be postponed beyond these waiting periods or performed with patients receiving dual antiplatelet therapy because withdrawal therapy increases 5 to 10 times the risk of postoperative myocardial infarction, stent thrombosis or death. The shorter the waiting period between revascularization and surgery the greater the risk of adverse cardiac events. The risk of surgical hemorrhage is increased approximately 20% by aspirin and 50% by clopidogrel. CONCLUSIONS: The risk of coronary thrombosis when antiplatelet agents are withdrawn before surgery is generally higher than the risk of surgical hemorrhage when antiplatelet agents are maintained. However, this issue has not yet been sufficiently evaluated in urological patients and in many instances during urological surgery the risk of bleeding can be dangerous. A thorough dialogue among surgeon, cardiologist and anesthesiologist is essential to determine all risk factors and define the best possible strategy for each patient.

Cardiac function assessed by transesophageal echocardiography during pectus excavatum repair.

BACKGROUND: We assessed end-diastolic right ventricular (RV) dimensions and left ventricular (LV) ejection fraction by use of intraoperative transesophageal echocardiography before and after surgical correction of pectus excavatum in adults. METHODS: A prospective study was conducted including 17 patients undergoing surgical correction of pectus excavatum according to the technique of Ravitch-Shamberger between 1999 and 2004. Intraoperative transesophageal echocardiography was performed under general anesthesia before and after surgery to assess end-diastolic RV dimensions and LV ejection fraction. The end-diastolic RV diameter and area were measured in four-chamber and RV inflow-outflow view, and the RV volume was calculated from these data. The LV was assessed by transgastric short-axis view, and its ejection fraction was calculated by use of the Teichholz formula. RESULTS: The end-diastolic RV diameter, area, and volume all significantly increased after surgery (mean values +/- SD, respectively: 2.4 +/- 0.8 cm versus 3.0 +/- 0.9 cm, p < 0.001; 12.5 +/- 5.2 cm(2) versus 18.4 +/- 7.5 cm(2), p < 0.001; and 21.7 +/- 11.7 mL versus 40.8 +/- 23 mL, p < 0.001). The LV ejection fraction also significantly increased after surgery (58.4% +/- 15% versus 66.2% +/- 6%, p < 0.001). CONCLUSIONS: Surgical correction of pectus excavatum according to Ravitch-Shamberger technique results in a significant increase in end-diastolic RV dimensions and a significantly increased LV ejection fraction.

Validity of an arterial pressure waveform analysis device: does the puncture site play a role in the agreement with intermittent pulmonary artery catheter thermodilution measurements?

OBJECTIVE: The measurement of cardiac output is a key element in the assessment of cardiac function. Recently, a pulse contour analysis-based device without need for calibration became available (FloTrac/Vigileo, Edwards Lifescience, Irvine, CA). This study was conducted to determine if there is an impact of the arterial catheter site and to investigate the accuracy of this system when compared with the pulmonary artery catheter using the bolus thermodilution technique (PAC). DESIGN: Prospective study. SETTING: The operating room of 1 university hospital. PARTICIPANTS: Twenty patients undergoing cardiac surgery. INTERVENTIONS: CO was determined in parallel by the use of the Flotrac/Vigileo systems in the radial and femoral position (CO_rad and CO_fem) and by PAC as the reference method. Data triplets were recorded at defined time points. The primary endpoint was the comparison of CO_rad and CO_fem, and the secondary endpoint was the comparison with the PAC. MEASUREMENTS AND MAIN RESULTS: Seventy-eight simultaneous data recordings were obtained. The Bland-Altman analysis for CO_fem and CO_rad showed a bias of 0.46 L/min, precision was 0.85 L/min, and the percentage error was 34%. The Bland-Altman analysis for CO_rad and PAC showed a bias of -0.35 L/min, the precision was 1.88 L/min, and the percentage error was 76%. The Bland-Altman analysis for CO_fem and PAC showed a bias of 0.11 L/min, the precision was 1.8 L/min, and the percentage error was 69%. CONCLUSION: The FloTrac/Vigileo system was shown to not produce exactly the same CO data when used in radial and femoral arteries, even though the percentage error was close to the clinically acceptable range. Thus, the impact of the introduction site of the arterial catheter is not negligible. The agreement with thermodilution was low.

A phase I pharmacokinetic study of hypoxic abdominal stop-flow perfusion with gemcitabine in patients with advanced pancreatic cancer and refractory malignant ascites.

PURPOSE: As no curative treatment for advanced pancreatic and biliary cancer with malignant ascites exists, new modalities possibly improving the response to available chemotherapies must be explored. This phase I study assesses the feasibility, tolerability and pharmacokinetics of a regional treatment of gemcitabine administered in escalating doses by the stop-flow approach to patients with advanced abdominal malignancies (adenocarcinoma of the pancreas, n = 8, and cholangiocarcinoma of the liver, n = 1). EXPERIMENTAL DESIGN: Gemcitabine at 500, 750 and 1,125 mg/m(2) was administered to three patients at each dose level by loco-regional chemotherapy, using hypoxic abdominal stop-flow perfusion. This was achieved by an aorto-caval occlusion by balloon catheters connected to an extracorporeal circuit. Gemcitabine and its main metabolite 2',2'-difluorodeoxyuridine (dFdU) concentrations were measured by high performance liquid chromatography with UV detection in the extracorporeal circuit during the 20 min of stop-flow perfusion, and in peripheral plasma for 420 min. Blood gases were monitored during the stop-flow perfusion and hypoxia was considered stringent if two of the following endpoints were met: pH /=1.35. The tolerability of this procedure was also assessed. RESULTS: Stringent hypoxia was achieved in four patients. Very high levels of gemcitabine were rapidly reached in the extracorporeal circuit during the 20 min of stop-flow perfusion, with C (max) levels in the abdominal circuit of 246 (+/-37%), 2,039 (+/-77%) and 4,780 (+/-7.3%) mug/ml for the three dose levels 500, 750 and 1,125 mg/m(2), respectively. These C (max) were between 13 (+/-51%) and 290 (+/-12%) times higher than those measured in the peripheral plasma. Similarly, the abdominal exposure to gemcitabine, calculated as AUC(t0-20), was between 5.5 (+/-43%) and 200 (+/-66%)-fold higher than the systemic exposure. Loco-regional exposure to gemcitabine was statistically higher in presence of stringent hypoxia (P < 0.01 for C (max) and AUC(t0-20), both normalised to the gemcitabine dose). Toxicities were acceptable considering the complexity of the procedure and were mostly hepatic; it was not possible to differentiate the respective contributions of systemic and regional exposures. A significant correlation (P < 0.05) was found between systemic C (max) of gemcitabine and the nadir of both leucocytes and neutrophils. CONCLUSIONS: Regional exposure to gemcitabine-the current standard drug for advanced adenocarcinoma of the pancreas-can be markedly enhanced using an optimised hypoxic stop-flow perfusion technique, with acceptable toxicities up to a dose of 1,125 mg/m(2). However, the activity of gemcitabine under hypoxic conditions is not as firmly established as that of other drugs such as mitomycin C, melphalan or tirapazamine. Further studies of this investigational modality, but with bioreductive drugs, are therefore warranted first to evaluate the tolerance in a phase I study and later on to assess whether it does improve the response to chemotherapy.

Perioperative use of anti-platelet drugs.

Performing a surgical procedure on a patient undergoing anti-platelet therapy raises a dilemma: is it safer to withdraw the drugs and reduce the haemorrhagic risk, or to maintain them and reduce the risk of myocardial ischaemic events? Based on recent clinical data, this review concludes that the risk of coronary thrombosis on anti-platelet drugs withdrawal is much higher than the risk of surgical bleeding when maintaining them. In secondary prevention, aspirin is a lifelong therapy and should never be stopped. Clopidogrel is mandatory as long as the coronary stents are not fully endothelialized, which takes 6-24 weeks depending on the technique used, but might be required for a longer period.

A novel technique using echocardiography to evaluate venous cannula performance perioperatively in CPB cardiac surgery.

OBJECTIVE: Transthoracic echocardiography (TTE) has been used clinically to disobstruct venous drainage cannula and to optimise placement of venous cannulae in the vena cava but it has never been used to evaluate performance capabilities. Also, little progress has been made in venous cannula design in order to optimise venous return to the heart lung machine. We designed a self-expandable Smartcanula (SC) and analysed its performance capability using echocardiography. METHODS: An epicardial echocardiography probe was placed over the SC or control cannula (CTRL) and a Doppler image was obtained. Mean (V(m)) and maximum (V(max)) velocities, flow and diameter were obtained. Also, pressure drop (DeltaP(CPB)) was obtained between the central venous pressure and inlet to venous reservoir. LDH and Free Hb were also compared in 30 patients. Comparison was made between the two groups using the student's t-test with statistical significance established when p<0.05. RESULTS: Age for the SC and CC groups were 61.6+/-17.6 years and 64.6+/-13.1 years, respectively. Weight was 70.3+/-11.6 kg and 72.8+/-14.4 kg, respectively. BSA was 1.80+/-0.2 m(2) and 1.82+/-0.2 m(2), respectively. CPB times were 114+/-53 min and 108+/-44 min, respectively. Cross-clamp time was 59+/-15 min and 76+/-29 min, respectively (p=NS). Free-Hb was 568+/-142 U/l versus 549+/-271 U/l post-CPB for the SC and CC, respectively (p=NS). LDH was 335+/-73 mg/l versus 354+/-116 mg/l for the SC and CC, respectively (p=NS). V(m) was 89+/-10 cm/s (SC) versus 63+/-3 cm/s (CC), V(max) was 139+/-23 cm/s (SC) versus 93+/-11 cm/s (CC) (both p<0.01). DeltaP(CPB) was 30+/-10 mmHg (SC) versus 43+/-13 mmHg (CC) (p<0.05). A Bland-Altman test showed good agreement between the two devices used concerning flow rate calculations between CPB and TTE (bias 300 ml+/-700 ml standard deviation). CONCLUSIONS: This novel Smartcanula design, due to its self-expanding principle, provides superior flow characteristics compared to classic two stage venous cannula used for adult CPB surgery. No detrimental effects were observed concerning blood damage. Echocardiography was effective in analysing venous cannula performance and velocity patterns.

Noninvasive Doppler-derived myocardial performance index in rats with myocardial infarction: validation and correlation by conductance catheter.

The rodent model of myocardial infarction (MI) is extensively used in heart failure studies. However, long-term follow-up of echocardiographic left ventricular (LV) function parameters such as the myocardial performance index (MPI) and its ratio with the fractional shortening (LVFS/MPI) has not been validated in conjunction with invasive indexes, such as those derived from the conductance catheter (CC). Sprague-Dawley rats with left anterior descending coronary artery ligation (MI group, n = 9) were compared with a sham-operated control group (n = 10) without MI. Transthoracic echocardiography (TTE) was performed every 2 wk over an 8-wk period, after which classic TTE parameters, especially MPI and LVFS/MPI, were compared with invasive indexes obtained by using a CC. Serial TTE data showed significant alterations in the majority of the noninvasive functional and structural parameters (classic and novel) studied in the presence of MI. Both MPI and LVFS/MPI significantly (P < 0.05 for all reported values) correlated with body weight (r = -0.58 and 0.76 for MPI and LVFS/MPI, respectively), preload recruitable stroke work (r = -0.61 and 0.63), LV end-diastolic pressure (LVEDP) (r = 0.82 and -0.80), end-diastolic volume (r = 0.61 and -0.58), and end-systolic volume (r = 0.46 and -0.48). Forward stepwise linear regression analysis revealed that, of all variables tested, LVEDP was the only independent determinant of MPI (r = 0.84) and LVFS/MPI (r = 0.83). We conclude that MPI and LVFS/MPI correlate strongly and better than the classic noninvasive TTE parameters with established, invasively assessed indexes of contractility, preload, and volumetry. These findings support the use of these two new noninvasive indexes for long-term analysis of the post-MI LV remodeling.

[Autologous blood pre-donation and perioperative use of erythropoietin]. / Prédonation autologue et place de l'érythropoïétine en phase périopératoire.

The general concept of blood saving covers a number of technical and pharmacological actions which all aim to maintain the erythrocyte mass of the patient, and of which blood transfusion is only one. Severe anemia (Hb <60-80 g/l) increases postoperative mortality and morbidity. However, its correction by blood transfusion tends to worsen the prognosis. It is therefore imperative to conserve the patient's blood by any means possible. Detecting anemia is of primary importance. Whenever possible, its cause should be identified and treated. Depending on the detected anemia, as well as the blood loss expected during surgery, the patient should receive EPO (anemia with foreseeable moderate blood loss), or autologous pre-donation associated with EPO (anemia with foreseeable large blood loss).

[Hemorrhage and transfusion: the case of Jehovah's witnesses]. / Hémorragie et transfusion: le cas des Témoins de Jéhovah.

For Jehovah Witness patients the additional responsibilities of surgeon, anesthetist and intensivist represent a particular challenge. A "therapeutic" contract needs to be established at the very outset specifying the commitment and undertaking of each party. The management of these patients requires that all the medical team demonstrate expertise in minimizing the risk of blood loss and in ensuring adequate oxygen transport to the tissues in the event of acute anaemia. The patient's autonomy must be respected at all times, including the availability of colleagues who agree with patients' demand. Above all, the entire medical team must respect the personal values of the patient despite any contradiction with their own values. This means that judgements based on values must be avoided in order to allow for the freedom of thought.

[Preoperative assessment in emergency cardiovascular surgery]. / Bilan préopératoire pour la chirurgie cardio-vasculaire en urgence.

In the emergency situation, preoperative patient work-up for cardio-vascular surgery is quite different from the elective setting. We have analyzed a consecutive series of 5576 cases out of which 823 underwent emergency procedures (14.8%). The most frequent problems requiring emergent intervention were peripheral vascular (186 cases; 22.6% of the emergent procedure), followed by coronary artery disease (156 cases; 19.0%), thoracic aortic aneurysms (86 cases; 10.4%), abdominal aortic aneurysms (54 cases; 6.6%), congenital heart disease (36 cases: 4.4%), heart and heart lung transplantation (31 cases; 3.8%), problems with cardiac rythm (25 cases: 3.0%), and others (267 cases: 32.4%). Classification by proportion of urgent procedures with reference to elective operations shows a different picture. As a matter of fact transplantations were always emergency procedures (100%), whereas repair of aortic dissections type A and B was an emergency procedure in 81.5%. Emergency thoracic and abdominal aortic aneurysm repair accounted for 30% and 20% respectively and the corresponding proportion for peripheral vascular surgery is 19%. However, emergency surgery for acute coronary ischemia, valvular and congenital heart disease accounted for somewhat less than 10% for each group of these pathologies. Systematic pre-operative diagnostic work-up is a recognized tool for procedure related risk assessment and superior management of diseases. However, hemodynamic instability and other time related events correlated with negative outcome, are the main driving forces for accelerated diagnostic pathways

Transfusion in the cardiac patient.

Transfusion guidelines in patients with coexisting cardiac diseases are similar to the ones in patients without such comorbidity, in that allogeneic blood transfusions most often are indicated at hemoglobin levels of less than 6.0 g/dL and hardly ever at hemoglobin levels greater than 10 g/dL. In the hemoglobin range of 6 to 10 g/dL, signs of impaired oxygenation should serve as transfusion indications, and such signs may be reached at higher hemoglobin values than in healthy patients. An inadequate oxygenation may become manifest globally in the form of a general hemodynamic instability with a tendency to hypotension and tachycardia despite normovolemia or an oxygen extraction of greater than 50%. An inadequate oxygenation in the form of myocardial ischemia may be manifested by new ST-segment depressions of greater than 0.1 mV, new ST-segment elevations greater than 0.2 mV, or new wall motion abnormalities in transesophageal echocardiography. Institutional guidelines also should consider local logistic characteristics such as the level of knowledge of physician and nurse staff caring for patients and the level of surveillance possible justifying eventually higher hemoglobin transfusion triggers, particularly in the postoperative period.

Partial inflow occlusion facilitates accurate deployment of thoracic aortic endografts.

PURPOSE: To present a maneuver consisting of temporary blockage of the venous return to the heart for accurate deployment of thoracic aortic endoprostheses. TECHNIQUE: During endovascular repairs in the thoracic aorta, an occluding balloon was introduced through the femoral vein into the right atrium under transesophageal echocardiographic control. The venous return through the inferior vena cava was temporarily blocked to reduce aortic flow during device deployment. The technique was applied in 21 patients with various lesions of the thoracic aorta. Partial inflow occlusion resulted in a mean systolic pressure of 49+/-6 mmHg and lasted for 52+/-14 seconds. Cardiac function was comparable to the preocclusion state, and no arrhythmias or ischemic events were encountered. In 7 procedures, inotropic or vasoconstrictor support was necessary after deployment. No complications related to the venous system were observed. The endoprostheses were precisely deployed at the target site in all patients. CONCLUSIONS: The force of aortic flow often impairs precise deployment of thoracic endoprostheses, resulting in distal displacement. Partial inflow occlusion provides precise control over the extent and duration of the hypotensive period, allowing accurate deployment of thoracic endoprostheses.

Automatic "respirator/weaning" with adaptive support ventilation: the effect on duration of endotracheal intubation and patient management.

UNLABELLED: Adaptive support ventilation (ASV) provides an automatic adaptation of the ventilator settings to patient's passive and active respiratory mechanics. In a randomized controlled study, we evaluated automatic respiratory weaning in ASV for early tracheal extubation after cardiac surgery. Eligible patients were assigned to either an ASV protocol or a standard one consisting of synchronized intermittent ventilation followed by pressure support. Eighteen patients completed the ASV protocol, and 16 completed the standard one. There were no differences between groups in perioperative characteristics, lengths of tracheal intubation and intensive care unit stay, and ventilatory variables, except less peak inspiratory pressure during the initial phase in ASV (17.5 +/- 0.8 versus 22.2 +/- 0.8 cm H(2)O; P < 0.01). ASV patients required fewer ventilatory settings manipulations (2.4 +/- 0.7 versus 4.0 +/- 0.8 manipulations per patient; P < 0.05) and endured less high-inspiratory pressure alarms (0.7 +/- 2.4 versus 2.9 +/- 3.0; P < 0.05). These results suggest that in this specific population of patients, automation of postoperative ventilation with ASV resulted in an outcome similar to the control group. The internal logic of the new device resulted in less manipulation of the setting and alarms that could simplify respiratory management. IMPLICATIONS: Adaptive support ventilation (ASV), a ventilatory mode providing automatic adjustment of the settings was compared with standard management for rapid tracheal extubation after cardiac surgery. The two approaches were equal in terms of outcome. In ASV, we observed fewer ventilator settings manipulations and a smaller amount of alarms, suggesting that this automatic mode may simplify postoperative respiratory management without delaying extubation.