Association of Cerebral Oximetry With Brain Ischemic Lesions and Functional Outcomes in Arch Repair.

BACKGROUND: This exploratory analysis of the randomized controlled Aortic Surgery Cerebral Protection Evaluation CardioLink-3 trial sought to determine if cerebral oximetry desaturation during elective proximal arch repair is associated with detrimental postoperative neuroradiologic and neurofunctional outcomes. METHODS: Cerebral oximetry and pre- and postoperative brain magnetic resonance imaging data from 101 participants were analyzed. Oximetry data from the trial allocation groups were compared; the relationships between cerebral oximetry indices and new ischemic cerebral lesions on magnetic resonance imaging and neurologic outcomes were also evaluated. RESULTS: Total cerebral desaturation events (>20% decrease from baseline) on the left (median [interquartile range], 1 [1-3] vs 1.5 [0.5-3] with innominate and axillary cannulation; P = .80) were comparable to those on the right (1 [1-3] vs 1 [0-3]; P = .75) as were the total area under the curve of desaturation (left, P = .61; right, P = .84). Seventy patients had new ischemic lesions, among whom 36 had new severe lesions. Total desaturation events and area under the curve of desaturation were similar in patients with and without new ischemic lesions or severe lesions. The nadir regional cerebral saturation was lower on the left (49% [41-56]) than the right (53% [44-59]); left desaturation episodes were associated with lower postoperative cognitive test scores (P = .004). CONCLUSIONS: The innominate and axillary cannulation techniques for elective proximal arch repair with unilateral antegrade cerebral perfusion were associated with similar occurrences of cerebral oximetry desaturation and neither were associated with new ischemic lesions.

Peri-operative pharmacokinetics of cefazolin prophylaxis during valve replacement surgery.

OBJECTIVE: There is little prospective data to guide effective dosing for antibiotic prophylaxis during surgery requiring cardiopulmonary bypass (CPB). We aim to describe the effects of CPB on the population pharmacokinetics (PK) of total and unbound concentrations of cefazolin and to recommend optimised dosing regimens. METHODS: Patients undergoing CPB for elective cardiac valve replacement were included using convenience sampling. Intravenous cefazolin (2g) was administered pre-incision and re-dosed at 4 hours. Serial blood and urine samples were collected and analysed using validated chromatography. Population PK modelling and Monte-Carlo simulations were performed using Pmetrics® to determine the fractional target attainment (FTA) of achieving unbound concentrations exceeding pre-defined exposures against organisms known to cause surgical site infections for 100% of surgery (100% fT>MIC). RESULTS: From the 16 included patients, 195 total and 64 unbound concentrations of cefazolin were obtained. A three-compartment linear population PK model best described the data. We observed that cefazolin 2g 4-hourly was insufficient to achieve the FTA of 100% fT>MIC for Staphylococcus aureus and Escherichia coli at serum creatinine concentrations ≤ 50 µmol/L and for Staphylococcus epidermidis at any of our simulated doses and serum creatinine concentrations. A dose of cefazolin 3g 4-hourly demonstrated >93% FTA for S. aureus and E. coli. CONCLUSIONS: We found that cefazolin 2g 4-hourly was not able to maintain concentrations above the MIC for relevant pathogens in patients with low serum creatinine concentrations undergoing cardiac surgery with CPB. The simulations showed that optimised dosing is more likely with an increased dose and/or dosing frequency.

Importance of assessing biomarkers and physiological parameters of anemia-induced tissue hypoxia in the perioperative period

Abstract Anemia is associated with increased risk of Acute Kidney Injury (AKI), stroke and mortality in perioperative patients. We sought to understand the mechanism(s) by assessing the integrative physiological responses to anemia (kidney, brain), the degrees of anemia-induced tissue hypoxia, and associated biomarkers and physiological parameters. Experimental measurements demonstrate a linear relationship between blood Oxygen Content (CaO2) and renal microvascular PO2 (y = 0.30x + 6.9, r2= 0.75), demonstrating that renal hypoxia is proportional to the degree of anemia. This defines the kidney as a potential oxygen sensor during anemia. Further evidence of renal oxygen sensing is demonstrated by proportional increase in serum Erythropoietin (EPO) during anemia (y = 93.806*10−0.02, r2= 0.82). This data implicates systemic EPO levels as a biomarker of anemia-induced renal tissue hypoxia. By contrast, cerebral Oxygen Delivery (DO2) is defended by a profound proportional increase in Cerebral Blood Flow (CBF), minimizing tissue hypoxia in the brain, until more severe levels of anemia occur. We hypothesize that the kidney experiences profound early anemia-induced tissue hypoxia which contributes to adaptive mechanisms to preserve cerebral perfusion. At severe levels of anemia, renal hypoxia intensifies, and cerebral hypoxia occurs, possibly contributing to the mechanism(s) of AKI and stroke when adaptive mechanisms to preserve organ perfusion are overwhelmed. Clinical methods to detect renal tissue hypoxia (an early warning signal) and cerebral hypoxia (a later consequence of severe anemia) may inform clinical practice and support the assessment of clinical biomarkers (i.e., EPO) and physiological parameters (i.e., urinary PO2) of anemia-induced tissue hypoxia. This information may direct targeted treatment strategies to prevent adverse outcomes associated with anemia.

Perioperative Optimization of the Cardiac Surgical Patient.

Perioperative optimization of cardiac surgical patients is imperative to reduce complications, utilize health care resources efficiently, and improve patient recovery and quality of life. Standardized application of evidence-based best practices can lead to better outcomes. Although many practices should be applied universally to all patients, there are also opportunities along the surgical journey to identify patients who will benefit from additional interventions that will further ameliorate their recovery. Enhanced recovery programs aim to bundle several process elements in a standardized fashion to optimize outcomes after cardiac surgery. A foundational concept of enhanced recovery is attaining a better postsurgical end point for patients, in less time, through achievement and maintenance in their greatest possible physiologic, functional, and psychological state. Perioperative optimization is a broad topic, spanning multiple phases of care and involving a variety of medical specialties and nonphysician health care providers. In this review we highlight a variety of perioperative care topics, in which a comprehensive approach to patient care can lead to improved results for patients, providers, and the health care system. A particular focus on patient-centred care is included. Although existing evidence supports all of the elements reviewed, most require further improvements in implementation, as well as additional research, before their full potential and usefulness can be determined.

Importance of assessing biomarkers and physiological parameters of anemia-induced tissue hypoxia in the perioperative period.

Anemia is associated with increased risk of Acute Kidney Injury (AKI), stroke and mortality in perioperative patients. We sought to understand the mechanism(s) by assessing the integrative physiological responses to anemia (kidney, brain), the degrees of anemia-induced tissue hypoxia, and associated biomarkers and physiological parameters. Experimental measurements demonstrate a linear relationship between blood Oxygen Content (CaO2) and renal microvascular PO2 (y = 0.30x + 6.9, r2 = 0.75), demonstrating that renal hypoxia is proportional to the degree of anemia. This defines the kidney as a potential oxygen sensor during anemia. Further evidence of renal oxygen sensing is demonstrated by proportional increase in serum Erythropoietin (EPO) during anemia (y = 93.806*10-0.02, r2 = 0.82). This data implicates systemic EPO levels as a biomarker of anemia-induced renal tissue hypoxia. By contrast, cerebral Oxygen Delivery (DO2) is defended by a profound proportional increase in Cerebral Blood Flow (CBF), minimizing tissue hypoxia in the brain, until more severe levels of anemia occur. We hypothesize that the kidney experiences profound early anemia-induced tissue hypoxia which contributes to adaptive mechanisms to preserve cerebral perfusion. At severe levels of anemia, renal hypoxia intensifies, and cerebral hypoxia occurs, possibly contributing to the mechanism(s) of AKI and stroke when adaptive mechanisms to preserve organ perfusion are overwhelmed. Clinical methods to detect renal tissue hypoxia (an early warning signal) and cerebral hypoxia (a later consequence of severe anemia) may inform clinical practice and support the assessment of clinical biomarkers (i.e., EPO) and physiological parameters (i.e., urinary PO2) of anemia-induced tissue hypoxia. This information may direct targeted treatment strategies to prevent adverse outcomes associated with anemia.

When to transfuse your acute care patient? A narrative review of the risk of anemia and red blood cell transfusion based on clinical trial outcomes.

This narrative review critically evaluates the evidence for risk of anemia and red blood cell (RBC) transfusion. For this purpose, it assesses large prospective randomized-controlled trials (RCTs) in medical, surgical, and critical care patient populations in which the impact of specific hemoglobin transfusion thresholds are compared. In these trials, the risks of anemia relative to those of RBC transfusion are assessed. The results of published systematic reviews and meta-analyses are also discussed. Lastly, recommendations for patient blood management and treatment of anemia are explored. The main conclusion of this review emphasizes that the decision to transfuse RBCs is complex and depends on the interaction between multiple factors including the balance between the risk of anemia and the risk of RBC transfusion, existing patient comorbidities, and medical and surgical exposures. The transfusion thresholds recommended by current guidelines vary for medical and surgical patient populations. Guidelines suggesting specific transfusion thresholds for different patient populations should be viewed as a starting point for making an informed decision about RBC transfusion. Alternatives to transfusion (i.e., patient blood management), biomarkers of anemia-induced tissue hypoxia, and transfusion alternatives should continue to be evaluated in large RCTs, with the goal of improving event-free survival in critically ill and perioperative patients.

RéSUMé: Ce compte rendu narratif évalue de façon critique les données probantes concernant le risque de l'anémie et de la transfusion d'érythrocytes. Pour ce faire, nous avons évalué des études randomisées contrôlées (ERC) prospectives de grande envergure réalisées auprès de populations de patients médicaux, chirurgicaux et de soins intensifs dans lesquelles l'impact de seuils spécifiques de transfusion d'hémoglobine est comparé. Dans ces études, les risques de l'anémie sont comparés aux risques de la transfusion d'érythrocytes. Les résultats des comptes rendus systématiques et méta-analyses publiés sont également présentés. Enfin, les recommandations concernant la gestion du sang des patients et le traitement de l'anémie sont explorées. La conclusion principale de ce compte rendu souligne que la décision de transfuser des érythrocytes est complexe et dépend de l'interaction de plusieurs facteurs, notamment de l'équilibre entre le risque de l'anémie et le risque de la transfusion d'érythrocytes, les comorbidités existantes du patient, et les risques médicaux et chirurgicaux. Les seuils de transfusion recommandés par les directives actuelles sont différents pour les populations de patients médicaux et chirurgicaux. Les directives proposant des seuils de transfusion spécifiques en fonction des différentes populations de patients devraient être considérées comme point de départ pour prendre une décision informée concernant la transfusion d'érythrocytes. Les alternatives à la transfusion (c.-à-d. la gestion du sang des patients), les biomarqueurs d'une hypoxie tissulaire induite par l'anémie et les alternatives à la transfusion devraient continuer à être évalués dans des ERC d'envergure, avec pour but l'amélioration de la survie sans complication des patients en état critique et périopératoires.