Management of bleeding and emergency invasive procedures in patients on dabigatran: Updated guidelines from the French Working Group on Perioperative Haemostasis (GIHP) - September 2016.

In 2013, the GIHP published guidelines for the management of severe haemorrhages and emergency surgery. This update applies to patients treated with dabigatran, with a bleeding complication or undergoing an urgent invasive procedure. It includes how to handle the available specific antidote (idarucizumab), when to measure dabigatran plasmatic concentration and when to use non-specific measures in these situations. It also includes guidelines on how to perform regional anaesthesia and analgesia procedures.

The place of fibrinogen concentrates in the management of perioperative bleeding: A position paper from the Francophone Working Group on Perioperative Haemostasis (GIHP).

The consumption of fibrinogen concentrates has been increasing steadily for several years in surgery, trauma and obstetrics. However, data from the literature are conflicting. The French Working Group on Perioperative Haemostasis (GIHP) proposes a position paper based on a narrative review of the literature, and addresses the following questions: What is the exact role of fibrinogen in haemostasis? Which rational support for the use of perioperative fibrinogen? Which thrombotic risk? What are the most recent professional recommendations on the use of fibrinogen concentrates? Then, evidence-based recommendations are proposed: 1) it is suggested not to administer prophylactic FC to prevent haemorrhage; 2) it is suggested not to use FC alone. Haemostatic treatment must be comprehensive, include other haemostatic treatments and must be limited in cases of severe active haemorrhage; 3) the GIHP suggests urgent measurement of fibrinogen plasma concentration in a biology laboratory or functional fibrinogen by viscoelastic methods. The choice between the two methods must be guided by the time to receive the results from a certified organisation with, in particular, authorisation to perform delocalised biologic examinations; 4) it is suggested not to administer FC when the fibrinogen concentration is superior to 1.5g/L or when there is a functional fibrinogen deficit (with the possible exception in obstetrics where the threshold could be 2.0g/L); 5) if FC are administered, an initial dose of 25-50mg/kg is proposed.

Management of antiplatelet therapy in patients undergoing elective invasive procedures. Proposals from the French Working Group on perioperative haemostasis (GIHP) and the French Study Group on thrombosis and haemostasis (GFHT). In collaboration with the French Society for Anaesthesia and Intensive Care Medicine (SFAR).

The French Working Group on Perioperative Haemostasis (GIHP) and the French Study Group on Haemostasis and Thrombosis (GFHT) in collaboration with the French Society for Anaesthesia and Intensive Care Medicine (SFAR) drafted up-to-date proposals for the management of antiplatelet therapy in patients undergoing elective invasive procedures. The proposals were discussed and validated by a vote; all proposals but one could be assigned with a high strength. The management of antiplatelet therapy is based on their indication and the procedure. The risk of bleeding related to the procedure can be divided into high, moderate and low categories depending on the possibility of performing the procedure in patients receiving antiplatelet agents (none, monotherapy and dual antiplatelet therapy respectively). If discontinuation of antiplatelet therapy is indicated before the procedure, a last intake of aspirin, clopidogrel, ticagrelor and prasugrel 3, 5, 5 and 7 days before surgery respectively is proposed. The thrombotic risk associated with discontinuation should be assessed according to each specific indication of antiplatelet therapy and is higher for patients receiving dual therapy for coronary artery disease (with further refinements based on a few well-accepted items) than for those receiving monotherapy for cardiovascular prevention, for secondary stroke prevention or for lower extremity arterial disease. These proposals also address the issue of the potential role of platelet functional tests and consider management of antiplatelet therapy for regional anaesthesia, including central neuraxial anaesthesia and peripheral nerve blocks, and for coronary artery surgery.

Effect of Xenon Anesthesia Compared to Sevoflurane and Total Intravenous Anesthesia for Coronary Artery Bypass Graft Surgery on Postoperative Cardiac Troponin Release: An International, Multicenter, Phase 3, Single-blinded, Randomized Noninferiority Trial.

BACKGROUND: Ischemic myocardial damage accompanying coronary artery bypass graft surgery remains a clinical challenge. We investigated whether xenon anesthesia could limit myocardial damage in coronary artery bypass graft surgery patients, as has been reported for animal ischemia models. METHODS: In 17 university hospitals in France, Germany, Italy, and The Netherlands, low-risk elective, on-pump coronary artery bypass graft surgery patients were randomized to receive xenon, sevoflurane, or propofol-based total intravenous anesthesia for anesthesia maintenance. The primary outcome was the cardiac troponin I concentration in the blood 24 h postsurgery. The noninferiority margin for the mean difference in cardiac troponin I release between the xenon and sevoflurane groups was less than 0.15 ng/ml. Secondary outcomes were the safety and feasibility of xenon anesthesia. RESULTS: The first patient included at each center received xenon anesthesia for practical reasons. For all other patients, anesthesia maintenance was randomized (intention-to-treat: n = 492; per-protocol/without major protocol deviation: n = 446). Median 24-h postoperative cardiac troponin I concentrations (ng/ml [interquartile range]) were 1.14 [0.76 to 2.10] with xenon, 1.30 [0.78 to 2.67] with sevoflurane, and 1.48 [0.94 to 2.78] with total intravenous anesthesia [per-protocol]). The mean difference in cardiac troponin I release between xenon and sevoflurane was -0.09 ng/ml (95% CI, -0.30 to 0.11; per-protocol: P = 0.02). Postoperative cardiac troponin I release was significantly less with xenon than with total intravenous anesthesia (intention-to-treat: P = 0.05; per-protocol: P = 0.02). Perioperative variables and postoperative outcomes were comparable across all groups, with no safety concerns. CONCLUSIONS: In postoperative cardiac troponin I release, xenon was noninferior to sevoflurane in low-risk, on-pump coronary artery bypass graft surgery patients. Only with xenon was cardiac troponin I release less than with total intravenous anesthesia. Xenon anesthesia appeared safe and feasible.

Management of direct oral anticoagulants in patients undergoing elective surgeries and invasive procedures: Updated guidelines from the French Working Group on Perioperative Hemostasis (GIHP) - September 2015.

Since 2011, data on patients exposed to direct oral anticoagulants (DOAs) while undergoing invasive procedures have accumulated. At the same time, an increased hemorrhagic risk during perioperative bridging anticoagulation without thrombotic risk reduction has been demonstrated. This has led the GIHP to update their guidelines published in 2011. For scheduled procedures at low bleeding risk, it is suggested that patients interrupt DOAs the night before irrespective of type of drug and to resume therapy six hours or more after the end of the invasive procedure. For invasive procedures at high bleeding risk, it is suggested to interrupt rivaroxaban, apixaban and edoxaban three days before. Dabigatran should be interrupted according to the renal function, four days and five days if creatinine clearance is higher than 50mL/min and between 30 and 50mL/min, respectively. For invasive procedures at very high bleeding risk such as intracranial neurosurgery or neuraxial anesthesia, longer interruption times are suggested. Finally, bridging with parenteral anticoagulation and measurement of DOA concentrations can no longer routinely be used.

Increased Extravascular Lung Water and Plasma Biomarkers of Acute Lung Injury Precede Oxygenation Impairment in Primary Graft Dysfunction After Lung Transplantation.

BACKGROUND: After lung transplantation (LT), early prediction of grade 3 pulmonary graft dysfunction (PGD) remains a research gap for clinicians. We hypothesized that it could be improved using extravascular lung water (EVLWi) and plasma biomarkers of acute lung injury. METHODS: After institutional review board approval and informed consent, consecutive LT recipients were included. Transpulmonary thermodilution-based EVLWi, plasma concentrations of epithelial (soluble receptor for advanced glycation endproducts [sRAGE]) and endothelial biomarkers (soluble intercellular adhesion molecule-1 and endocan [full-length and cleaved p14 fragment]) were obtained before and after LT (0 [H0], 6, 12, 24, 48 and 72 hours after pulmonary artery unclamping). Grade 3 PGD was defined according to the International Society for Lung and Heart Transplantation definition, combining arterial oxygen partial pressure (PaO2)/inspired fraction of oxygen (FiO2) ratio and chest X-rays. Association of clinical risk factors, EVLWi and biomarkers with grade 3 PGD was analyzed under the Bayesian paradigm, using logistic model and areas under the receiver operating characteristic curves (AUCs). RESULTS: In 47 LT recipients, 10 developed grade 3 PGD, which was obvious at H6 in 8 cases. Clinical risk factors, soluble intercellular adhesion molecule-1 and endocan (both forms) were not associated with grade 3 PGD. Significant predictors of grade 3 PGD included (1) EVLWi (optimal cutoff, 13.7 mL/kg; AUC, 0.74; 95% confidence interval [CI], 0.48-0.99), (2) PaO2/FiO2 ratio (optimal cutoff, 236; AUC, 0.68; 95% CI, 0.52-0.84), and (3) sRAGE (optimal cutoff, 11 760 pg/mL; AUC, 0.66; 95% CI, 0.41-0.91) measured at H0. CONCLUSIONS: Immediate postreperfusion increases in EVLWi and sRAGE along with impaired PaO2/FiO2 ratios were early predictors of grade 3 PGD at or beyond 6 hours and may trigger early therapeutic interventions.

Identifying optimal heparin management during cardiopulmonary bypass in obese patients: A prospective observational comparative study.

BACKGROUND: The heparin regimen providing anticoagulation during cardiopulmonary bypass (CPB) is usually adapted to total body weight (TBW), but may be inaccurate in obese patients in whom TBW exceeds their ideal body weight. OBJECTIVES: The objective is to compare the effects of heparin injection based on TBW on haemostatic parameters between obese and nonobese patients during cardiac surgery and to calculate the optimal heparin regimen. DESIGN: Prospective comparative study. SETTING: University hospital. PATIENTS: Two groups of 50 patients (BMI≥ or <30 kg m) were included in the study over a 9-month period in 2013. The study started on 27 February 2013. INTERVENTIONS: An unfractionated heparin (UFH) bolus of 300 IU kg TBW was injected before initiation of CPB followed by additional doses (50 to 100 IU kg) to maintain a target activated coagulation time (ACT) of at least 400 s. MAIN OUTCOME MEASURES: ACT and plasma heparin concentration were measured at different time points after initiation of, and weaning from CPB. RESULTS: Obese patients received higher initial and total doses of heparin (P < 0.0001). Plasma heparin concentrations were significantly higher in obese patients at each time point (P < 0.001) and reached very high values after the initial bolus (5.90 vs. 4.48 IU ml, P < 0.0001). The relationship between plasma heparin concentration and ACT after the initial bolus was not linear and followed an asymptotic regression curve. Haemoglobin concentration decreased intraoperatively to a greater extent in the obese group (P < 0.001). No significant differences in postoperative bleeding or global transfusion requirements were observed. CONCLUSION: The standard heparin regimen based on TBW in obese patients during CPB results in excessive plasma heparin concentrations and a significant intraoperative decrease in haemoglobin concentration. ACT monitoring was not accurate in identifying this excess dosage. An initial bolus of 340 IU kg ideal body weight would achieve a heparin concentration of 4.5 IU ml, similar to that observed in nonobese patients. Further investigations are warranted to confirm this heparin regimen.

Once versus twice daily injection of enoxaparin for thromboprophylaxis in bariatric surgery: effects on antifactor Xa activity and procoagulant microparticles. A randomized controlled study.

BACKGROUND: The optimal scheme of thromboprophylaxis in bariatric surgery remains uncertain, because clinical practice is different between countries and randomized trials are lacking. OBJECTIVES: The primary objective of this randomized multicenter study was to determine the optimal regimen of enoxaparin providing an antifactor Xa peak activity between .3 and .5 IU/mL at equilibrium and to evaluate the course of procoagulant microparticles (MPs). SETTING: University hospital. METHODS: A total of 164 patients scheduled for gastric bypass were allocated to 3 groups (A, B, and C) of enoxaparin treatment (4000, 6000, or 2×4000 IU, respectively). Antifactor Xa activity was measured before and 4 hours after each injection from D0 to D2. Doppler screening of the lower limbs was performed at D1, D9, and D30. Bleeding (BE) and thrombotic events (TE) were recorded during the first postoperative month. Total MPs were measured at D0, D9, and D30. MPs of leucocyte, platelet, and granulocyte origin were assessed in one third of the patients from each group. The 3 groups were compared by ANOVA. RESULTS: A total of 135 patients were analyzed. The equilibrium of antifactor Xa peak levels was obtained 52 hours after the presurgery injection and 12.8%, 56.4%, and 27.3% of the patients reached the target in groups A, B, and C, respectively (P<.001). No TE was detected. BE occurred in 1, 2, and 6 patients in groups A, B, and C, respectively). Total MPs remained unchanged over time. While no significant variation was observed in the other groups, platelet GP1 b(+)-MPs increased (P = .01) at D9 in group C, suggesting an incomplete control of anticoagulation leading to cell activation and procoagulant MP release that was confirmed by the higher MP levels measured at D30 (P = .04). CD66(+)-MPs were also highly elevated at J9 and D30 in group C indicating a granulocyte contribution. CONCLUSIONS: This study shows that a single dose of enoxaparin 6000 IU/d allowed most of the patients to reach the target range of antifactor Xa activity without increasing the bleeding risk, with the most likely efficient reduction of procoagulant MPs. (Surg Obes Relat Dis 2015;0:000-000.) © 2015 American Society for Metabolic and Bariatric Surgery. All rights reserved.

Compliance with guidelines for the perioperative management of vitamin K antagonists.

INTRODUCTION: Perioperative vitamin K antagonist management is an issue of concern in many countries. The availability of best practice guidelines meets health professionals' needs, but compliance is uncertain and should be assessed. MATERIALS AND METHODS: Our aim was to assess practitioner compliance with the guidelines on perioperative VKA management issued by the French National Authority for Health through a national register set up in partnership with the French College of Anaesthetists and Intensivists. Seven sections of data entry were focused on perioperative management of VKAs for elective or emergency procedures. High-risk patients were identified. Compliance with guidelines was calculated per item RESULTS: 932 charts were completed between October 2009 and December 2010. VKA therapy was interrupted in 74% (622/837) of elective procedures and bridged in 69% cases (428/622) mainly with LMWH. According to guidelines, bridging was strongly recommended in 39% high-risk patients (175/394) but 13% of these (23/175) received no bridging. Bridging was overused in 60% of low risk patients (242/406). Other compliance rates were as follows: (i) administration of therapeutic enoxaparin doses (=200IU/kg/day): only 18% of high-risk patients (18/98), (ii) INR measurement on evening prior to the procedure 65% (525/803), (iii) concomitant prothrombin complex concentrate and vitamin K administration in emergency surgery 24% (21/87), (iv) postoperative therapeutic enoxaparin doses: only 20% despite widespread prescription. The incidence rate of bleeding and thrombotic events was 7.1% and 0.96% respectively. CONCLUSIONS: These poor compliance rates with guidelines suggest that the knowledge-to-action transfer plan was inadequate and that further interventions are required.

Post-intubation tracheal rupture: poor healing of the tracheal wall.

PURPOSE: To describe tracheal rupture after orotracheal intubation assisted by a tracheal tube introducer. CLINICAL FEATURES: A 73-yr-old morbidly obese female patient with a history of hypertension underwent a total knee replacement. There were no anticipated signs of difficult intubation. Orotracheal intubation was attempted twice by direct laryngoscopy, and a Boussignac bougie was used as a tube exchanger for the second attempt. Seven hours after tracheal extubation, the patient became dyspneic and showed a large subcutaneous emphysema. A chest x-ray and computerized tomography scan revealed rupture of the posterior tracheal wall. The distal part of the injury was 26.5 cm from the patient's teeth and 0.5 cm from the carina (i.e., beyond the normal location of the tracheal tube tip) and extended to the origin of the right main bronchus, where the tip of the Boussignac bougie was probably pushed. Formation of an endotracheal sac occurred during the first two weeks after intubation, accompanied by dyspnea and alveolar hypoventilation, but symptoms resolved favourably with conservative management. CONCLUSION: The tracheal rupture was attributed to airway manipulations, and the distal location of the lesion suggests that the cause was the Boussignac bougie rather than the tracheal tube. Long-term healing of the injury was satisfactory, although the patient continued to complain of dyspnea one year after the rupture.

Venous thromboembolism prophylaxis in patients undergoing abdominal or pelvic surgery for cancer--a real-world, prospective, observational French study: PRéOBS.

INTRODUCTION: Data on the epidemiology and prevention of venous thromboembolism in patients undergoing abdominal or pelvic cancer surgery in real practice are limited. The primary objective of this observational study was to describe the thromboprophylactic strategy implemented in routine practice. The main secondary objective was to assess the incidence of outcomes. MATERIALS AND METHODS: Patients admitted to public or private hospitals for abdominal or pelvic cancer surgery were included between November 2009 and November 2010; endoscopic route for surgery was the only exclusion criterion. Study outcomes were recorded at hospital discharge and at routine follow-up (generally 9±3weeks). RESULTS: 2380 patients (mean±SD age: 66.4±11.6years, women: 36.8%) admitted to hospital for abdominal (47.8%), urological (41%), or gynaecological (11.2%) cancer surgery were included in the analysis. Of these, 2179 had data available at study end. Perioperative antithrombotic prophylaxis, consisting mainly of low-molecular-weight heparin, was given to 99.5% of patients. At hospital discharge, thromboprophylaxis was continued in 91.7% of patients, 57.4% receiving a 4-6week prophylaxis. This management strategy was associated with an overall venous thromboembolic event rate of 1.9%, 34.7% of events occurring after discharge. Incidences of fatal bleeding, bleeding in a critical organ and bleeding necessitating re-intervention were 0.1%, 0.3% and 1.7%, respectively. Overall mortality was 1.5%. CONCLUSIONS: Thromboprophylaxis is routinely used in French patients undergoing major cancer surgery. For more than a third of patients, however, treatment duration did not comply with best-practice recommendations, which might explain the non-negligible rate of thromboembolic complications still observed in this patient population.

[New direct oral anticoagulants and venous thromboprophylaxis]. / Les nouveaux anticoagulants dans la prévention de la thrombose veineuse.

The new direct oral anticoagulants currently available are dabigatran, rivaroxaban and apixaban. These three drugs have been labeled in France for the prevention of venous thromboembolism after elective orthopaedic surgery including total hip or knee arthroplastly. Rivaroxaban is also labeled for the secondary prevention of thrombosis recurrence following an initial acute event. Pharmacologic properties of these drugs are reminded as well as the results of the main studies having conducted to their approval.

Impact of a phosphorylcholine-coated cardiac bypass circuit on blood loss and platelet function: a prospective, randomized study.

Platelet dysfunction due to cardiopulmonary bypass (CPB) surgery increases the risk of bleeding. This study analyzed the effect of a phosphorylcholine (PC)-coated CPB circuit on blood loss, transfusion needs, and platelet function. We performed a prospective, randomized study at Strasbourg University Hospital, which included 40 adults undergoing coronary artery bypass graft surgery (CABG) (n = 20) or mitral valve repair (n = 20) using CPB. Patients were randomized either to PC-coated CPB or uncoated CPB (10 CABG patients and 10 mitral valve repair patients in each group). Blood loss and transfusion needs were evaluated intra- and postoperatively. Markers of platelet activation and thrombin generation were measured at anesthesia induction, at the beginning and end of CPB, on skin closure, and on days 0, 1, and 5. Comparisons were made by Student's t test or covariance analysis (significance threshold p < or = .05). Blood loss was significantly lower in the PC group during the first 6 postoperative hours (171 +/- 102 vs. 285 +/- 193 mL, p = .024), at the threshold of significance from 6-24 hours (p = .052), and similar in both groups after 24 hours. During CPB, platelet count decreased by 48% in both groups. There was no difference in markers of platelet activation, thrombin generation, or transfusion needs between the two groups. Norepinephrine use was more frequent in the control group (63% vs. 33%) but not significantly. PC-coating of the CPB surface reduced early postoperative bleeding, especially in CABG patients, but had no significant effect on platelet function because of large interindividual variations that prevented the establishment of a causal relationship.

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.

Intra-operative paravertebral block for postoperative analgesia in thoracotomy patients: a randomized, double-blind, placebo-controlled study.

OBJECTIVE: Epidural analgesia is the gold standard for post-thoracotomy pain relief but is contraindicated in certain patients. An alternative is paravertebral block. We investigated whether ropivacaine, administered through a paravertebral catheter placed by the surgeon, reduced postoperative pain. METHODS: In a randomized double-blind study, adult patients with a paravertebral catheter placed by the thoracic surgeon after thoracotomy were randomly assigned to receive through this catheter, either a 0.1 mlkg(-1) bolus of 0.5% ropivacaine, followed by a continuous infusion of 0.1 mlkg(-1)h(-1) for 48 h, or saline at the same scheme of administration. Patients also benefited from patient-controlled analgesia with intravenous morphine (bolus 1mg, lockout time 7 min), paracetamol, and nefopam. The primary endpoint was pain intensity on a visual analog scale at rest and on coughing. Secondary endpoints were total morphine consumption and side effects during the first 48 postoperative hours. Surgeons, anesthesiologists, and all the nurses and caring staff involved in this study were blinded. Solutions of saline and ropivacaine were prepared identically by the central pharmacy, without any possible identification of the product. RESULTS: Forty-seven patients with contraindications to epidural anesthesia were included. There were no significant differences between the groups receiving ropivacaine and saline in terms of pain severity at rest and on coughing, mean postoperative morphine consumption (45.7 mg for ropivacaine, 43.2mg in controls), and incidence of morphine-related side effects (nausea and vomiting, urinary retention, pruritus, respiratory rate, and sedation). CONCLUSIONS: Paravertebral block using a catheter placed by the thoracic surgeon was ineffective on postoperative pain after thoracotomy and did not confirm the analgesic effect that has been observed after percutaneous catheter placement. A direct comparison of these two placement methods is required.

Anesthesia for other endovascular stenting.

PURPOSE OF REVIEW: Diagnostic and therapeutic endovascular stenting tended to expand in the last decade. The anesthetist may be asked to participate in the management of these patients with severe associated comorbidities complicating the delivery of anesthesia. This review describes current vascular stentings performed in the radiology suite and their relevant consequences interesting the anesthetist. RECENT FINDINGS: Most of these procedures can be performed under local anesthesia associated or not with moderate sedation. Carotid stenting is as well tolerated as carotid surgery but those selected patients who may benefit from it are not clearly identified. Endovascular stenting of the aorta avoids major surgical trauma and decreases its consequences. The procedure requires light anesthesia but careful monitoring. Prior thoracic aortic replacement and the length of zone numbers covered by the stent graft are risk factors for spinal ischemia that may lead to paraplegia. Cerebrospinal fluid drainage, evoked potential, and S100 beta monitoring may help to prevent this complication or detect it earlier. Transjugular intrahepatic portosystemic shunt is efficient in treating acute variceal bleeding and for secondary prevention. Postoperative encephalopathy represents the main postprocedural complication. SUMMARY: Literature review provides little information about anesthetic management of extracranial endovascular stentings. Knowledge of indication and consequences is mandatory for anesthetists in charge of these patients.