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Methodist DeBakey Cardiovascular Journal 2023Vasoplegia is a condition characterized by persistent low systemic vascular resistance despite a normal or high cardiac index, resulting in profound and uncontrolled... (Review)
Review
Vasoplegia is a condition characterized by persistent low systemic vascular resistance despite a normal or high cardiac index, resulting in profound and uncontrolled vasodilation. Vasoplegia may occur due to various conditions, including cardiac failure, sepsis, and post-cardiac surgery. In the cardiac cohort, multiple risk factors for vasoplegia have been identified. Several factors contribute to the pathophysiology of this condition, and various mechanisms have been proposed, including nitric oxide, adenosine, prostanoids, endothelins, the renin-angiotensin-aldosterone system, and hydrogen sulfide. Early identification and prompt management of vasoplegia is crucial to prevent development of shock. This review expands upon the different vasopressors used in management of vasoplegia, including catecholamines such as norepinephrine, dopamine, epinephrine, phenylephrine, and other agents including vasopressin, methylene blue, angiotensin II, hydroxocobalamin, vitamin C, thiamine, and corticosteroids (ie, hydrocortisone). It also emphasizes the importance of conducting further research and making advancements in treatment regimens for vasoplegia.
Topics: Humans; Vasoplegia; Epinephrine; Norepinephrine; Phenylephrine; Sepsis
PubMed: 37547893
DOI: 10.14797/mdcvj.1245 -
Circulation Mar 2022Recent studies have established that CCR2 (C-C chemokine receptor type 2) marks proinflammatory subsets of monocytes, macrophages, and dendritic cells that contribute to...
BACKGROUND
Recent studies have established that CCR2 (C-C chemokine receptor type 2) marks proinflammatory subsets of monocytes, macrophages, and dendritic cells that contribute to adverse left ventricle (LV) remodeling and heart failure progression. Elucidation of the effector mechanisms that mediate adverse effects of CCR2 monocytes, macrophages, and dendritic cells will yield important insights into therapeutic strategies to suppress myocardial inflammation.
METHODS
We used mouse models of reperfused myocardial infarction, angiotensin II and phenylephrine infusion, and diphtheria toxin cardiomyocyte ablation to investigate CCL17 (C-C chemokine ligand 17). We used knockout mice, flow cytometry, RNA sequencing, biochemical assays, cell trafficking studies, and in vivo cell depletion to identify the cell types that generate CCL17, define signaling pathways that controlled its expression, delineate the functional importance of CCL17 in adverse LV remodeling and heart failure progression, and determine the mechanistic basis by which CCL17 exerts its effects.
RESULTS
We demonstrated that CCL17 is expressed in CCR2 macrophages and cluster of differentiation 11b conventional dendritic cells after myocardial infarction, angiotensin II and phenylephrine infusion, and diphtheria toxin cardiomyocyte ablation. We clarified the transcriptional signature of CCL17 macrophages and dendritic cells and identified granulocyte-macrophage colony-stimulating factor (GM-CSF) signaling as a key regulator of CCL17 expression through cooperative activation of STAT5 (signal transducer and activator of transcription 5) and canonical NF-κB (nuclear factor κ-light-chain-enhancer of activated B cells) signaling. deletion resulted in reduced LV remodeling, decreased myocardial fibrosis and cardiomyocyte hypertrophy, and improved LV systolic function after myocardial infarction and angiotensin II and phenylephrine infusion. We observed increased abundance of regulatory T cells (Tregs) in the myocardium of injured knockout mice. CCL17 inhibited Treg recruitment through biased activation of CCR4. CCL17 activated Gq signaling and CCL22 (C-C chemokine ligand 22) activated both Gq and ARRB (β-arrestin) signaling downstream of CCR4. CCL17 competitively inhibited CCL22 stimulated ARRB signaling and Treg migration. We provide evidence that Tregs mediated the protective effects of deletion on myocardial inflammation and adverse LV remodeling.
CONCLUSIONS
These findings identify CCL17 as a proinflammatory mediator of CCR2 macrophages and dendritic cells and suggest that inhibition of CCL17 may serve as an effective strategy to promote Treg recruitment and suppress myocardial inflammation.
Topics: Angiotensin II; Animals; Chemokine CCL17; Diphtheria Toxin; Heart Failure; Humans; Inflammation; Ligands; Mice; Mice, Inbred C57BL; Mice, Knockout; Myocardial Infarction; Phenylephrine; T-Lymphocytes, Regulatory; Ventricular Remodeling
PubMed: 35113652
DOI: 10.1161/CIRCULATIONAHA.121.055888 -
Anesthesiology Apr 2024The treatment of intraoperative hypotension with phenylephrine may impair cerebral perfusion through vasoconstriction, which has been linked to postoperative delirium....
BACKGROUND
The treatment of intraoperative hypotension with phenylephrine may impair cerebral perfusion through vasoconstriction, which has been linked to postoperative delirium. The hypothesis was that intraoperative administration of phenylephrine, compared to ephedrine, is associated with higher odds of postoperative delirium.
METHODS
A total of 103,094 hospitalized adults undergoing general anesthesia for noncardiac, non-neurosurgical procedures between 2008 and 2020 at two tertiary academic healthcare networks in Massachusetts were included in this multicenter hospital registry study. The primary exposure was the administration of phenylephrine versus ephedrine during surgery, and the primary outcome was postoperative delirium within 7 days. Multivariable logistic regression analyses adjusted for a priori defined confounding variables including patient demographics, comorbidities, and procedural factors including magnitude of intraoperative hypotension were applied.
RESULTS
Between the two healthcare networks, 78,982 (76.6%) patients received phenylephrine, and 24,112 (23.4%) patients received ephedrine during surgery; 770 patients (0.8%) developed delirium within 7 days. The median (interquartile range) total intraoperative dose of phenylephrine was 1.0 (0.2 to 3.3) mg and 10.0 (10.0 to 20.0) mg for ephedrine. In adjusted analyses, the administration of phenylephrine, compared to ephedrine, was associated with higher odds of developing postoperative delirium within 7 days (adjusted odds ratio, 1.35; 95% CI, 1.06 to 1.71; and adjusted absolute risk difference, 0.2%; 95% CI, 0.1 to 0.3%; P = 0.015). A keyword and manual chart review-based approach in a subset of 45,465 patients further validated these findings (delirium incidence, 3.2%; adjusted odds ratio, 1.88; 95% CI, 1.49 to 2.37; P < 0.001). Fractional polynomial regression analysis further indicated a dose-dependent effect of phenylephrine (adjusted coefficient, 0.08; 95% CI, 0.02 to 0.14; P = 0.013, per each μg/kg increase in the cumulative phenylephrine dose).
CONCLUSIONS
The administration of phenylephrine compared to ephedrine during general anesthesia was associated with higher odds of developing postoperative delirium. Based on these data, clinical trials are warranted to determine whether favoring ephedrine over phenylephrine for treatment of intraoperative hypotension can reduce delirium after surgery.
Topics: Adult; Humans; Phenylephrine; Ephedrine; Vasoconstrictor Agents; Emergence Delirium; Retrospective Studies; Hypotension
PubMed: 37725759
DOI: 10.1097/ALN.0000000000004774 -
International Journal of Obstetric... Aug 2021Spinal anesthesia is the standard for elective cesarean section but spinal anesthesia-induced hypotension remains an important problem. Accurate prediction of... (Review)
Review
BACKGROUND
Spinal anesthesia is the standard for elective cesarean section but spinal anesthesia-induced hypotension remains an important problem. Accurate prediction of hypotension could enhance clinical decision-making, alter management, and facilitate early intervention. We performed a systematic review of predictors of spinal anesthesia-induced hypotension and their predictive value during cesarean section.
METHODS
PubMed, Embase, Cochrane Library, Google Scholar and Web of Science databases were searched for prospective observational studies assessing the diagnostic accuracy of predictors of spinal anesthesia-induced hypotension in elective cesarean section. The quality of studies was assessed and predictors were grouped in domains based on the type of predictor.
RESULTS
Thirty-eight studies (n=3086 patients) were included. In most studies, patients received 500-1000 mL crystalloid preload or 500-2000 mL crystalloid coload. Vasopressors for post-spinal hypotension were boluses of ephedrine 5-15 mg and/or phenylephrine 25-100 µg in most studies. The hypotension rate varied from 29% to 80% based on the definition. For analysis, >30 predictors were classified into seven domains: demographic characteristics, baseline hemodynamic variables, baseline sympathovagal balance, postural stress testing, peripheral perfusion indices, blood volume and fluid responsiveness indices, and genetic polymorphism.
CONCLUSIONS
Environmental and individual factors increased outcome variability, which restricted the value of the autonomic nervous system and peripheral perfusion indices for prediction of spinal anesthesia-induced hypotension. Supine stress tests may reflect parturients' cardiovascular tolerance during hemodynamic fluctuations and may optimize the predictive value of static state predictors. Future research for predicting spinal anesthesia-induced hypotension should focus on composite and dynamic parameters during the supine stress tests.
Topics: Anesthesia, Obstetrical; Anesthesia, Spinal; Cesarean Section; Colloids; Female; Humans; Hypotension; Hypotension, Controlled; Observational Studies as Topic; Phenylephrine; Pregnancy; Vasoconstrictor Agents
PubMed: 34034957
DOI: 10.1016/j.ijoa.2021.103175 -
Critical Care (London, England) Feb 2020Vasoplegic syndrome is a common occurrence following cardiothoracic surgery and is characterized as a high-output shock state with poor systemic vascular resistance. The... (Review)
Review
Vasoplegic syndrome is a common occurrence following cardiothoracic surgery and is characterized as a high-output shock state with poor systemic vascular resistance. The pathophysiology is complex and includes dysregulation of vasodilatory and vasoconstrictive properties of smooth vascular muscle cells. Specific bypass machine and patient factors play key roles in occurrence. Research into treatment of this syndrome is limited and extrapolated primarily from that pertaining to septic shock, but is evolving with the expanded use of catecholamine-sparing agents. Recent reports demonstrate potential benefit in novel treatment options, but large clinical trials are needed to confirm.
Topics: Adrenal Cortex Hormones; Angiotensin II; Ascorbic Acid; Cardiac Surgical Procedures; Dopamine; Enzyme Inhibitors; Epinephrine; Humans; Methylene Blue; Norepinephrine; Phenylephrine; Sympathomimetics; Vascular Resistance; Vasoconstrictor Agents; Vasoplegia; Vasopressins
PubMed: 32019600
DOI: 10.1186/s13054-020-2743-8 -
Cureus Nov 2023Nasal congestion is a common issue stemming from various factors such as allergies and anatomical variations. Allergic rhinitis frequently leads to nasal congestion. The... (Review)
Review
Nasal congestion is a common issue stemming from various factors such as allergies and anatomical variations. Allergic rhinitis frequently leads to nasal congestion. The pathophysiology involves inflammation, swelling, and mucus production in the nasal mucosa. Multiple treatments are available, including oral phenylephrine, an over-the-counter or prescription option. However, the effectiveness and safety of phenylephrine have been subjects of debate. This systematic review aims to provide an updated perspective on the efficacy of oral phenylephrine versus placebo in addressing nasal congestion in adults. We conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines, a systematic review involving searches on PubMed, Cochrane, and Scopus databases. Inclusion/exclusion criteria were defined to identify high-quality studies. The focus was on randomized controlled trials (RCTs) and case-control studies published in English between 1998 and 2023, involving adult populations. The interventions compared oral phenylephrine with placebo or standard care, with outcomes centering on changes in nasal congestion symptoms and nasal airway resistance. We identified four articles that met the criteria. These studies exhibited varied designs and populations. The findings consistently indicated that phenylephrine was not more effective than a placebo in relieving nasal congestion. This systematic review demonstrates that oral phenylephrine did not offer substantial relief from nasal congestion compared to a placebo in adults. The studies featured diverse designs, yet the prevailing conclusion was that phenylephrine's efficacy was limited. Safety assessments showed no life-threatening adverse events, with common side effects including headaches and mild discomfort. In summary, this systematic review indicates that oral phenylephrine is not significantly more effective than a placebo in alleviating nasal congestion in adults. Clinicians should explore alternative treatment options, considering the review's limitations. Additional research may be needed to clarify the role of oral phenylephrine in managing nasal congestion.
PubMed: 38125218
DOI: 10.7759/cureus.49074 -
Circulation Research Jan 2020Hypertrophied hearts switch from mainly using fatty acids (FAs) to an increased reliance on glucose for energy production. It has been shown that preserving FA oxidation...
RATIONALE
Hypertrophied hearts switch from mainly using fatty acids (FAs) to an increased reliance on glucose for energy production. It has been shown that preserving FA oxidation (FAO) prevents the pathological shift of substrate preference, preserves cardiac function and energetics, and reduces cardiomyocyte hypertrophy during cardiac stresses. However, it remains elusive whether substrate metabolism regulates cardiomyocyte hypertrophy directly or via a secondary effect of improving cardiac energetics.
OBJECTIVE
The goal of this study was to determine the mechanisms of how preservation of FAO prevents the hypertrophic growth of cardiomyocytes.
METHODS AND RESULTS
We cultured adult rat cardiomyocytes in a medium containing glucose and mixed-chain FAs and induced pathological hypertrophy by phenylephrine. Phenylephrine-induced hypertrophy was associated with increased glucose consumption and higher intracellular aspartate levels, resulting in increased synthesis of nucleotides, RNA, and proteins. These changes could be prevented by increasing FAO via deletion of ACC2 (acetyl-CoA-carboxylase 2) in phenylephrine-stimulated cardiomyocytes and in pressure overload-induced cardiac hypertrophy in vivo. Furthermore, aspartate supplementation was sufficient to reverse the antihypertrophic effect of ACC2 deletion demonstrating a causal role of elevated aspartate level in cardiomyocyte hypertrophy. 15N and 13C stable isotope tracing revealed that glucose but not glutamine contributed to increased biosynthesis of aspartate, which supplied nitrogen for nucleotide synthesis during cardiomyocyte hypertrophy.
CONCLUSIONS
Our data show that increased glucose consumption is required to support aspartate synthesis that drives the increase of biomass during cardiac hypertrophy. Preservation of FAO prevents the shift of metabolic flux into the anabolic pathway and maintains catabolic metabolism for energy production, thus preventing cardiac hypertrophy and improving myocardial energetics.
Topics: Acetyl-CoA Carboxylase; Animals; Aspartic Acid; Cardiomegaly; Cells, Cultured; Fatty Acids; Glucose; Male; Mice; Myocytes, Cardiac; Rats; Rats, Wistar
PubMed: 31709908
DOI: 10.1161/CIRCRESAHA.119.315483 -
Chest Oct 2022Atrial fibrillation (AF) is a common complication of sepsis. It is unclear whether norepinephrine, an α- and β-agonist, and phenylephrine, an α-agonist, are...
BACKGROUND
Atrial fibrillation (AF) is a common complication of sepsis. It is unclear whether norepinephrine, an α- and β-agonist, and phenylephrine, an α-agonist, are associated with different heart rates among patients with sepsis and AF.
RESEARCH QUESTION
Among patients with sepsis and AF, what is the difference in heart rate after phenylephrine initiation vs norepinephrine initiation?
STUDY DESIGN AND METHODS
With the use of an extensive database, we identified patients with sepsis and AF at the time of norepinephrine or phenylephrine initiation. We estimated the difference in heart rate between patients who received phenylephrine or norepinephrine 1 and 6 h after vasopressor initiation with the use of multivariable-adjusted linear regression, tested for effect modification by heart rate, and stratified by baseline heart rate ≥ 110 or < 110 beats/min. Secondary outcomes included conversion to sinus rhythm, bradycardia, vasopressor duration, ICU and hospital length of stay, and hospital death. Exploratory analyses were adjusted for practices that occurred after vasopressor initiation; sensitivity analyses used interrupted time series to estimate the difference in average heart rate between patients who received phenylephrine or norepinephrine.
RESULTS
Among 1847 patients with sepsis and AF, 946 patients (51%) received norepinephrine, and 901 patients (49%) received phenylephrine. After multivariable adjustment, phenylephrine was associated with a lower heart rate at 1 h (-4 beats/min; 95% CI, -6 to -1; P < .001) and 6 h (-4 beats/min; 95% CI, -6 to -1; P = .004). Higher heart rate before vasopressor administration was associated with larger heart rate reduction in patients who received phenylephrine compared with norepinephrine. There were no differences in secondary outcomes. Results were similar in exploratory and sensitivity analyses.
INTERPRETATION
In patients with sepsis and AF, the initiation of phenylephrine was associated with modestly lower heart rate compared with norepinephrine. Heart rate at vasopressor initiation appeared to be an important effect modifier. Whether modest reductions in heart rate are associated with clinical outcomes requires further study.
Topics: Atrial Fibrillation; Bradycardia; Heart Rate; Humans; Norepinephrine; Phenylephrine; Sepsis; Shock, Septic; Vasoconstrictor Agents
PubMed: 35526604
DOI: 10.1016/j.chest.2022.04.147