Perioperative bleeding remains a major complication during and after surgery, resulting in increased morbidity and mortality. The principal causes of non-vascular sources of haemostatic perioperative bleeding are a preexisting undetected bleeding disorder, the nature of the operation itself, or acquired coagulation abnormalities secondary to haemorrhage, haemodilution, or haemostatic factor consumption. In the bleeding patient, standard therapeutic approaches include allogeneic blood product administration, concomitant pharmacologic agents, and increasing application of purified and recombinant haemostatic factors. Multiple haemostatic changes occur perioperatively after trauma and complex surgical procedures including cardiac surgery and liver transplantation. Novel strategies for both prophylaxis and therapy of perioperative bleeding include tranexamic acid, desmopressin, fibrinogen and prothrombin complex concentrates. Point-of-care patient testing using thromboelastography, rotational thromboelastometry, and platelet function assays has allowed for more detailed assessment of specific targeted therapy for haemostasis. Strategic multimodal management is needed to improve management, reduce allogeneic blood product administration, and minimize associated risks related to transfusion.
COVID-19 is a syndrome that includes more than just isolated respiratory disease, as severe acute respiratory syndromecoronavirus 2 (SARS-CoV2) also interacts with the cardiovascular, nervous, renal, and immune system at multiple levels, increasing morbidity in patients with underlying cardiometabolic conditions and inducing myocardial injury or dysfunction. Emerging evidence suggests that patients with the highest rate of morbidity and mortality following SARS-CoV2 infection have also developed a hyperinflammatory syndrome (also termed cytokine release syndrome). We lay out the potential contribution of a dysfunction in autonomic tone to the cytokine release syndrome and related multiorgan damage in COVID-19. We hypothesize that a cholinergic anti-inflammatory pathway could be targeted as a therapeutic avenue.
Prothrombin complex concentrates (PCCs) contain vitamin K-dependent clotting factors (II, VII, IX and X) and are marketed as 3 or 4 factor-PCC formulations dependent on the concentrations of Factor VII. PCCs rapidly restore deficient coagulation factor concentrations to achieve hemostasis, but as with all procoagulants, the effect is balanced against thromboembolic risk. The latter is dependent on both the dose of PCCs and individual patient prothrombotic predisposition. PCCs are Food and Drug Administration approved for the reversal of vitamin K antagonists in the setting of coagulopathy or bleeding and therefore can be administered in these patients when urgent surgery is required. There is, however, a growing experience with the off-label use of PCCs to treat patients with surgical coagulopathic bleeding. Despite their increasing use, there are limited prospective data related to the safety, efficacy, and dosing of PCCs for this indication. PCC administration in the perioperative setting may be tailored to the individual patient based on laboratory and clinical variables, including point-of-care coagulation testing, in order to balance hemostatic benefits while minimizing prothrombotic risk. Importantly, in patients with perioperative bleeding, other considerations should include treating additional sources of coagulopathy such as hypofibrinogenemia, thrombocytopenia and platelet disorders, or surgical sources of bleeding. Thromboembolic risk from excessive PCC dosing may be present well into the postoperative period after hemostasis is achieved owing to the relatively long half-life of prothrombin (Factor II, 60 – 72 hours). The integration of PCCs into comprehensive perioperative coagulation treatment algorithms for refractory bleeding is increasingly reported, but further studies are needed to better evaluate the safe and effective administration of these factor concentrates.
Andexanet alfa is a specific reversal agent for Factor Xa inhibitors. The molecule is a recombinant protein analog of factor Xa that binds to Factor Xa inhibitors and antithrombin:LMWH complex but does not trigger prothrombotic activity. In ex vivo, animal, and volunteer human studies, andexanet alfa (AnXa) was able to dose-dependently reverse Factor Xa inhibition and restore thrombin generation for the duration of drug administration. Further trials are underway to examine its safety and efficacy in the population of patients experiencing FXa inhibitor-related bleeding.
ENHANCED RECOVERY After Surgery (ERAS) is an international effort to develop perioperative programs aimed at optimizing patient outcomes and healthcare delivery efficiency. These programs are composed of intervention bundles based on the principles of best practice, standardized and consistent healthcare delivery, regular audit, and team feedback, all with a patient-centered focus. Implementation of such programs has resulted in patient and healthcare benefits, including promising early results within the cardiac surgical community. [1][2][3][4] There have been recent concerns that old dogma, typically rooted in clinical anecdotes and minimal peer-reviewed evidence, will be replaced with new dogma under the umbrella of "enhanced recovery" without validation in cardiac surgical patients. 5 An imprudent "changing of the guard" is a justifiable concern with any practice update. Gathering current evidence-based best practices was a key motivation for the creation of the original colorectal ERAS protocol.The Society for Enhanced Recovery After Cardiac Surgery (ERAS Cardiac) recently published "Guidelines for Perioperative Care in Cardiac Surgery" based on a systematic review and multidisciplinary consensus. 6 Twenty-two recommendations were graded according to currently accepted standards for level of evidence (LOE) and confidence of recommendation (COR) (Table 1). 7,8 The authors of this editorial represent the current anesthesiologist membership of the ERAS Cardiac Society. We have chosen a subset of the recommendations to discuss, including why each is important for patients during their recovery and which future steps are required to solidify the supporting evidence for each recommendation.
MTB should be considered during vasoplegic syndrome in cardiac surgery with cardiopulmonary bypass and usage may be more effective in an early critical window, prior to end-organ hypoperfusion. Other perioperative scenarios of MTB use show promise, but additional studies are required to develop formative conclusions.
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