The Year in Cardiothoracic Critical Care: Selected Highlights from 2019.

In 2019, cardiothoracic and vascular critical care remained an important focus and subspecialty. This article continues the annual series to review relevant contributions in postoperative critical care that may affect the cardiac anesthesiologist. Herein, the pertinent literature published in 2019 is explored and organized by organ system.

Incidence of healthcare-associated infections in patients with fever during the first 48 hours after decannulation from veno-venous extracorporeal membrane oxygenation.

INTRODUCTION: Fevers following decannulation from veno-venous extracorporeal membrane oxygenation often trigger an infectious workup; however, the yield of this workup is unknown. We investigated the incidence of post-veno-venous extracorporeal membrane oxygenation decannulation fever as well as the incidence and nature of healthcare-associated infections in this population within 48 hours of decannulation. METHODS: All patients treated with veno-venous extracorporeal membrane oxygenation for acute respiratory failure who survived to decannulation between August 2014 and November 2018 were retrospectively reviewed. Trauma patients and bridge to lung transplant patients were excluded. The highest temperature and maximum white blood cell count in the 24 hours preceding and the 48 hours following decannulation were obtained. All culture data obtained in the 48 hours following decannulation were reviewed. Healthcare-associated infections included blood stream infections, ventilator-associated pneumonia, and urinary tract infections. RESULTS: A total of 143 patients survived to decannulation from veno-venous extracorporeal membrane oxygenation and were included in the study. In total, 73 patients (51%) were febrile in the 48 hours following decannulation. Among this cohort, seven healthcare-associated infections were found, including five urinary tract infections, one blood stream infection, and one ventilator-associated pneumonia. In the afebrile cohort (70 patients), four healthcare-associated infections were found, including one catheter-associated urinary tract infection, two blood stream infections, and one ventilator-associated pneumonia. In all decannulated patients, the majority of healthcare-associated infections were urinary tract infections (55%). No central line-associated blood stream infections were identified in either cohort. When comparing febrile to non-febrile cohorts, there was a significant difference between pre- and post-decannulation highest temperature (p < 0.001) but not maximum white blood cell count (p = 0.66 and p = 0.714) between the two groups. Among all positive culture data, the most commonly isolated organism was Klebsiella pneumoniae (41.7%) followed by Escherichia coli (33%). Median hospital length of stay and time on extracorporeal membrane oxygenation were shorter in the afebrile group compared to the febrile group; however, this did not reach a statistical difference. CONCLUSION: Fever is common in the 48 hours following decannulation from veno-venous extracorporeal membrane oxygenation. Differentiating infection from non-infectious fever in the post-decannulation veno-venous extracorporeal membrane oxygenation population remains challenging. In our febrile post-decannulation cohort, the incidence of healthcare-associated infections was low. The majority were diagnosed with a urinary tract infection. We believe obtaining cultures in febrile patients in the immediate decannulation period from veno-venous extracorporeal membrane oxygenation has utility, and even in the absence of other clinical suspicion, should be considered. However, based on our data, a urinalysis and urine culture may be sufficient as an initial work up to identify the source of infection.

Elevated fibrinogen, von Willebrand factor, and Factor VIII confer resistance to dilutional coagulopathy and activated protein C in normal pregnant women.

BACKGROUND: Gestational changes in coagulation factor concentrations include elevations in fibrinogen, Factor VIII, and von Willebrand factor (vWF). We hypothesised that blood samples from term pregnant (TP) subjects are less prone to coagulation disturbances from haemodilution compared with those from non-pregnant (NP) females. METHODS: Blood samples were collected from 15 NP and 15 TP subjects. In vitro haemodilution with normal saline was assessed by modified Clauss fibrinogen assay, factor activity, flow-chamber assay, and thromboelastometry. The impact of human fibrinogen concentrate (hFC), cryoprecipitate, and vWF/Factor VIII (FVIII) concentrate replacement in diluted TP and NP blood was compared. Thrombin generation and activated protein C sensitivity were assessed. RESULTS: TP blood contained twice the concentrations of fibrinogen, FVIII, and vWF relative to NP blood (P<0.0001). Platelet thrombus formation (PTF) under flow was reduced by 99.2% and 69.2% in diluted NP and TP blood, respectively. Platelet thrombus formation was partially restored by adding vWF/FVIII, but not hFC or cryoprecipitate. Fibrin clot firmness approached the threshold of 10 mm in diluted NP blood, and clot firmness was effectively restored by hFC, but not by vWF/FVIII. In the presence of thrombomodulin, peak thrombin generation was decreased by 86.7% in NP plasma, but by 31.8% in TP plasma (P<0.0001 vs NP plasma), indicating reduced activated protein C sensitivity in TP plasma. Both elevated FVIII and haemodilution contributed to activated protein C insensitivity. CONCLUSIONS: Our in vitro model showed relative resistance of TP blood to dilutional coagulation changes with respect to platelet adhesion, fibrin polymerisation, and thrombin generation. Careful therapeutic monitoring for different pro-haemostatic agents in pregnant women is warranted.

Factor IX from prothrombin complex concentrate augments low dose tissue factor-triggered thrombin generation in vitro.

BACKGROUND: Prothrombin complex concentrate (PCC) is increasingly used to correct acquired coagulopathy in trauma and surgery. Dosing of PCC is guided by the prothrombin time, which only reflects the onset of thrombin generation, but does not account for variations in intrinsic pathway coagulation factors, including factor IX (FIX). We hypothesised that FIX contained in PCC could strongly influence thrombin generation patterns. METHODS: Pooled normal, FIX-deficient, and warfarinised plasma were used to analyse the effects of FIX contained in PCC. PCC was evaluated at final concentrations of 0.2 and 0.4 IU ml-1 in FIX-deficient and normal plasma, and at 0.6 IU ml-1 in warfarinised plasma with elevated FVIII (1.5 IU ml-1), 40% dilution with saline, or both. The effects on thrombin generation were assessed by measuring both procoagulant and inhibitory segments. RESULTS: FIX-deficient plasma had lower peak thrombin generation [30.6 (20.5-35.8) nM vs 130.2 (107-168) nM] and endogenous thrombin potential [472 (391-532) nM vs 1096 (958-1190) nM] than normal plasma. PCC addition resulted in significant increases of peak thrombin generation [81.8 (37.3-98.3) nM] and endogenous thrombin potential [808 (472-842) nM] in FIX-deficient plasma. The combination of FVIII and PCC resulted in greater increases relative to each agent alone, restoring normal thrombin generation. After 40% dilution, adding PCC, FVIII, or both, to FIX-deficient plasma increased peak thrombin generation, and prolonged the inhibitory phase of the endogenous thrombin potential. CONCLUSIONS: FIX derived from PCC strongly enhances tissue factor-triggered thrombin generation in the presence of elevated FVIII activity. Haemodilution further enhances procoagulant effects of FIX and FVIII by slowing down inhibition of procoagulant enzymes. Dosing of PCC per prothrombin time may underestimate PCC's procoagulant potential because it does not account for intrinsic tenase or antithrombin activity.

Perioperative management of rare coagulation factor deficiency states in cardiac surgery.

Rare bleeding disorders (RBDs) include the hereditary deficiency of fibrinogen, factor (F)II, FV, FV + FVIII, FVII, FX, FXI or FXIII. RBDs do not confer a protective effect against atheromatous plaque formation, and thus the need for cardiovascular (CV) surgery in RBD patients is expected to increase with improved healthcare access (diagnosis and management) and longevity of the population. Clinical data regarding the management of RBDs in this setting are sparse, but the perioperative care team is obliged to gain a better understanding on available biological and pharmacological hemostatic agents. Perioperative management of RBDs in CV surgery is further complicated by heparin anticoagulation, haemodilution, and consumption of procoagulant and anticoagulant proteins associated with cardiopulmonary bypass (CPB). The aims of this review are to summarize pathophysiology of RBDs and laboratory monitoring pertinent to CV surgery, available factor replacement agents, and to provide the framework for perioperative coagulation management of RBD patients.