Ludmil Mitrev

Vasoplegia is a form of distributive shock that commonly occurs after cardiac surgery involving cardiopulmonary bypass. Although a formal definition does not exist, it is generally characterized by low systemic vascular resistance with a maintained or elevated cardiac index that tends to be resistant to treatment with fluid or vasopressor. Postoperative vasoplegia in cardiac surgery patients is associated with increased morbidity and mortality. This article reviews the current understanding of the pathophysiology of vasoplegia in cardiac surgery, including risk factors for its development, and evolving strategies for prediction, diagnosis, and treatment. Prominent preoperative risk factors include patient demographics (older age, male sex, elevated body mass index), comorbid conditions (heart failure with reduced ejection fraction, chronic kidney disease, anemia, infective endocarditis, hemodynamic instability, thyroid dysfunction, diabetes mellitus, tobacco use), medications (renin-angiotensin-aldosterone axis blockers, calcium channel blockers, beta-blockers, inotropes, antiplatelets and anticoagulants, amiodarone, diuretics, anesthetic agents), and the type of surgical procedure performed. Prominent intraoperative risk factors include the use of cardiopulmonary bypass, blood product transfusion, and poor temperature control. Multiple biomarkers and dynamic monitoring systems are being studied as predictors for the development of vasoplegia. An overview of available treatments is presented along with up-to-date evidence supporting their use in multimodal vasopressor regimens.

Myocardial work and oxygen consumption (MVO ₂ ) are tightly coupled. The patient's physiological state, presence of disease, heart rate, and microvascular control of oxygen delivery all combine to maintain this relationship. The myocardial efficiency (MyoEff) of the heart is determined by the ratio of stroke‐work (SW) divided by MVO ₂ , whereas mechanical efficiency (ME) is derived from the left ventricular pressure‐volume loop construct and is the ratio of SW to pressure‐volume area. The need to collect invasive data limited the ability to perform human studies, but the development of noninvasive tools such as positron emission tomography (PET) combined with echocardiography led to a resurgence in this field of study. We summarize the current understanding of the significance of MyoEff and ME as outcomes predictors after aortic valve replacement and as parameters in cardiovascular health, highlighting their potential for improving risk stratification and guiding prophylactic interventions.

Monitoring cardiac output (CO) is helpful in the perioperative management of the patient with severe mitral regurgitation (MR). We assessed the accuracy and precision of the Cheetah CO monitor in patients with moderate or severe MR undergoing right and left heart catheterization as part of their pre-operative evaluation for mitral valve surgery. Cheetah CO was obtained concurrently with thermodilution CO (TD CO). Bias data was non-normally distributed; therefore, a non-parametric equivalent to Bland and Altman limits of agreement was used. Additionally, the proportions of differences between the experimental and reference method that were ≤ 0.5 L/min, ≤ 1 L/min, and >1 L/min were calculated. Twenty-seven subjects were enrolled and completed the study. The median difference between Cheetah and TD CO measurements was − 0.82 L/min, and the 5th and 95th centiles were − 6.05 L/min and 3.25 L/min, respectively. Of all differences, 25.9%, 51.9%, and 48.1% were ≤ 0.5 L/min, ≤ 1 L/min, and > 1 L/min. No proportional bias was present. We conclude that the Cheetah CO measurements in patients with moderate to severe MR cannot be used interchangeably with TD CO due to a large bias and imprecision.

Monitoring cardiac output (CO) is helpful in the perioperative management of the patient with severe mitral regurgitation (MR). We assessed the accuracy and precision of the Cheetah CO monitor in patients with moderate or severe MR undergoing right and left heart catheterization as part of their pre-operative evaluation for mitral valve surgery. Cheetah CO was obtained concurrently with thermodilution CO (TD CO). Bias data was non-normally distributed; therefore, a non-parametric equivalent to Bland and Altman limits of agreement was used. Additionally, the proportions of differences between the experimental and reference method that were ≤ 0.5 L/min, ≤ 1 L/min, and > 1L/min were calculated. Twenty-seven subjects were enrolled and completed the study. The median difference between Cheetah and TD CO measurements was − 0.82 L/min, and the 5th and 95th centiles were − 6.05 L/min and 3.25 L/min, respectively. Of all differences, 25.9%, 51.9%, and 48.1% were ≤ 0.5 L/min, ≤ 1 L/min, and > 1 L/min. No proportional bias was present. We conclude that the Cheetah CO measurements in patients with moderate to severe MR cannot be used interchangeably with TD CO due to a large bias and imprecision.

Background: To mitigate perioperative hypothermia, patients can be warmed preoperatively and intraoperatively with forced-air warming (FAW) and conductive warming (CW) methods. We examined the association of four combinations of pre- and intraoperative CW and FAW with the magnitude of intraoperative hypothermia. Methods: We conducted a prospective randomized trial at a tertiary healthcare center in the United States (trial registration number ISRCTN23065394). Patients were randomized to 4 arms based on the following pre/intraoperative warming combinations: (1) CW/CW, (2) FAW/FAW, (3) no active prewarming (NAPW)/CW, (4) NAPW/FAW. Body temperature was measured using an esophageal probe. The area under the temperature curve (AUC) below 36°C was calculated according to the trapezoidal rule and quantified intraoperative hypothermia. A mixed model was used to estimate differences in AUC between the 4 arms. Results: 182 patients were analyzed. Patients in the NAPW/FAW arm had the highest AUC values while those in the CW/CW arm had the lowest. AUC values [median (Q1, Q3] were as follows: CW/CW = 4.7 (0, 26.6); FAW/FAW = 8.0 (0, 30.8); NAPW/CW = 7.4 (0, 27.1); NAPW/FAW = 19.9 (5.0, 44.3). Mixed model results showed significant lower AUC values in CW/CW and NAPW/CW when compared to NAPW/FAW. The ratio of mean AUC [95% CI] between CW/CW vs NAPW/FAW was 0.49 [0.24, 0.98], 51% lower, and between NAPW/CW and NAPW/FAW, 0.46 [0.23, 0.91], 54% lower. When the AUC was normalized to the duration of surgery (AUC/case duration in°C, or “relative AUC”), significant lower relative AUC values were observed between FAW/FAW vs NAPW/FAW (48% lower, p = 0.0419) and NAPW/CW vs NAPW/FAW (48% lower, p = 0.0407). Conclusions: CW is more effective than FAW at reducing intraoperative hypothermia when FAW is used without prewarming. When patients are actively prewarmed, CW and FAW show no difference in their ability to maintain patient temperature.

BACKGROUND: Patient perception of physician compassion may be associated with improved health outcomes, yet it is unclear whether it is associated with postoperative pain reduction or improved patient experience metrics in same-day surgery patients. We hypothesized that higher anesthesiologist compassion during the preanesthesia interview, rated by patients, is associated with lower postoperative pain via the anxiety pathway in same-day surgery patients. We also performed exploratory correlation analysis to assess whether compassion was associated with less opioid consumption and improved patient experience in same-day surgery patients. METHODS: We conducted a single-center, prospective, observational cohort study in American Society of Anesthesiologists (ASA) physical status I to III patients scheduled to undergo same-day surgery with anesthesia. Compassion was scored using a validated 5-item tool. State anxiety (SA) and trait anxiety (TA) were measured using the State-Trait Anxiety Inventory. Pain scores were obtained using a 0 to 10 Likert scale. Daily opioid use was recorded. Patient experience was assessed using the Consumer Assessment of Healthcare Providers and Systems Outpatient and Ambulatory Surgery Survey (OAS CAHPS) and the Surgical Care CAHPS. Mediation analysis was used to assess the association between compassion and pain scores via the anxiety pathway. Spearman correlation was performed to test for association between the compassion score and the secondary outcomes. RESULTS: A total of 147 subjects completed the study with a median age of 50 years and 81% female. Fifty percent underwent breast surgery, 35% abdominal surgery, and the rest underwent gynecological and urological surgeries. The median (Q1–Q3) postoperative pain scores on postoperative days 0 and 3 days later were 4 (1.5–6) and 3 (1–5), respectively. Mediation analysis results showed a same-day anxiety-mediated effect (95% confidence interval [CI]) of compassion on pain of −0.08 (−0.13 to −0.02), attributing to 9% of the total effect. On postoperative day 0, an increase in compassion was associated with a significant average drop in pain of between 0.02 and 0.13. In addition, higher compassion was correlated with better patient experience metrics (ρ= −0.53 [95% CI, −0.64 to −0.39]). CONCLUSIONS: The study results suggest that an anxiety-mediated pathway exists through which compassionate care may help improve the patient’s perception of postoperative pain on the day of surgery (before discharge from the hospital). Higher compassion was also associated with better patient experience metrics.

Introduction: Vascular aging is associated with a loss of aortic compliance (C_A), which results in increased left ventricular pressure–volume area (PVA), stroke work (SW) and myocardial oxygen consumption (MVO₂). Myocardial efficiency (MyoEff) is derived from the PVA and MVO₂ construct, which includes potential energy (PE). However, the SW/MVO₂ ratio does not include PE and provides a more accurate physiologic measure. Methods: We used a modified computational model (CM) to assess PVA and SW and calculate MVO₂ using a pressure-work index (e MVO₂), to derive MyoEff–PVA and MyoEff–SW metrics. Phase I evaluated five levels of human C_A from normal (N) to stiff (S) at 80 bpm, and Phase II evaluated two levels of C_A (N and S) at three heart rates (60, 100, and 140 bpm). Results: During Phase I, MyoEff–PVA increased from 20.7 to 31.2%, and MyoEff–SW increased from 14.8 to 18.9%. In Phase II, during the N setting coupled with increases in the heart rate, the MyoEff–PVA decreased from 29.4 to 14.8 to 9.5%; the MyoEff–SW also decreased from 22.5 to 10.3 to 5.9%. As expected, during the S setting, MyoEff–PVA decreased from 45.5 to 22.9 to 14.8; a similar effect occurred with the MyoEff–SW, demonstrating a decrease from 29.9 to 13.9 to 7.9%, respectively. Conclusions: The CM provided insights into a simple and clinically relevant calculation for assessing MyoEff. The agreement on the CM metrics aligns with studies conducted previously in the clinical setting.

Parkinson’s disease (PD) is a progressive neurodegenerative disorder that affects over 1% of population over age 60. It is defined by motor and nonmotor symptoms including a spectrum of cognitive impairments known as Parkinson’s disease dementia (PDD). Currently, the only US Food and Drug Administration-approved treatment for PDD is rivastigmine, which inhibits acetylcholinesterase and butyrylcholinesterase increasing the level of acetylcholine in the brain. Due to its limited efficacy and side effect profile, rivastigmine is often not prescribed, leaving patients with no treatment options. PD has several derangements in neurotransmitter pathways (dopaminergic neurons in the nigrostriatal pathway, kynurenine pathway (KP), acetylcholine, α7 nicotinic receptor, and N-methyl-D-aspartate (NMDA) receptors) and rivastigmine is only partially effective as it only targets one pathway. Kynurenic acid (KYNA), a metabolite of tryptophan metabolism, affects the pathophysiology of PDD in multiple ways. Both galantamine (α7 nicotinic receptor) and memantine (antagonist of the NMDA subtype of the glutamate receptor) are KYNA modulators. When used in combination, they target multiple pathways. While randomized controlled trials (RCTs) with each drug alone for PD have failed, the combination of galantamine and memantine has demonstrated a synergistic effect on cognitive enhancement in animal models. It has therapeutic potential that has not been adequately assessed, warranting future randomized controlled trials. In this review, we summarize the KYNA-centric model for PD pathophysiology and discuss how this treatment combination is promising in improving cognitive function in patients with PDD through its action on KYNA.

Transcatheter aortic valve replacement (TAVR) has become the dominant procedural modality for aortic valve replacement in the United States. The reported rates of neurological complications in patients undergoing TAVR have changed over time and are dependent on diagnostic definitions and modalities. Most strokes after TAVR are likely embolic in origin, and the incidence of stroke has decreased over time. Studies have yielded conflicting results when comparing stroke rates between TAVR and surgical aortic valve replacement (SAVR), especially due to differences in diagnostic criteria and neurocognitive testing. In this narrative review, we summarize the available data on the incidence of stroke, delirium, and cognitive decline after TAVR and highlight potential areas in need of future research. We also discuss silent cerebral ischemic lesions (SCILs) and their association with a decline in postoperative neurocognitive status after TAVR. Finally, we describe that the risk of delirium and postoperative decline is increased when nonfemoral access routes are used, and we highlight the need for standardized imaging and valid, repeatable methodologies to assess cognitive changes after TAVR.