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Resuscitation Oct 2023The Vasopressin and Methylprednisolone for In-Hospital Cardiac Arrest (VAM-IHCA) trial demonstrated a significant improvement in return of spontaneous circulation (ROSC)... (Randomized Controlled Trial)
Randomized Controlled Trial
INTRODUCTION
The Vasopressin and Methylprednisolone for In-Hospital Cardiac Arrest (VAM-IHCA) trial demonstrated a significant improvement in return of spontaneous circulation (ROSC) with no clear effect on long-term outcomes. The objective of the current manuscript was to evaluate the hemodynamic effects of intra-cardiac arrest vasopressin and methylprednisolone during the first 24 hours after ROSC.
METHODS
The VAM-IHCA trial randomized patients with in-hospital cardiac arrest to a combination of vasopressin and methylprednisolone or placebo during the cardiac arrest. This study is a post hoc analysis focused on the hemodynamic effects of the intervention after ROSC. Post-ROSC data on the administration of glucocorticoids, mean arterial blood pressure, heart rate, blood gases, vasopressor and inotropic therapy, and sedation were collected. Total vasopressor dose between the two groups was calculated based on noradrenaline-equivalent doses for adrenaline, phenylephrine, terlipressin, and vasopressin.
RESULTS
The present study included all 186 patients who achieved ROSC in the VAM IHCA-trial of which 100 patients received vasopressin and methylprednisolone and 86 received placebo. The number of patients receiving glucocorticoids during the first 24 hours was 22/86 (26%) in the placebo group and 14/100 (14%) in the methylprednisolone group with no difference in the cumulative hydrocortisone-equivalent dose. There was no significant difference between the groups in the mean cumulative noradrenaline-equivalent dose (vasopressin and methylprednisolone: 603 ug/kg [95CI% 227; 979] vs. placebo: 651 ug/kg [95CI% 296; 1007], mean difference -48 ug/kg [95CI% -140; 42.9], p = 0.30), mean arterial blood pressure, or lactate levels. There was no difference between groups in arterial blood gas values and vital signs.
CONCLUSION
Treatment with vasopressin and methylprednisolone during cardiac arrest caused no difference in mean arterial blood pressure, vasopressor use, or arterial blood gases within the first 24 hours after ROSC when compared to placebo.
Topics: Humans; Methylprednisolone; Cardiopulmonary Resuscitation; Heart Arrest; Vasopressins; Vasoconstrictor Agents; Hemodynamics; Norepinephrine; Hospitals; Gases
PubMed: 37543161
DOI: 10.1016/j.resuscitation.2023.109922 -
Journal of Clinical Monitoring and... Oct 2023It has been reported that cerebral oxygenation (ScO) measured by near infrared spectroscopy is maintained or increased by treatment with ephedrine, whereas almost all... (Observational Study)
Observational Study
It has been reported that cerebral oxygenation (ScO) measured by near infrared spectroscopy is maintained or increased by treatment with ephedrine, whereas almost all previous reports demonstrated that phenylephrine reduced ScO. As the mechanism of the latter, the interference of the extracranial blood flow, that is extracranial contamination, has been suspected. Accordingly, in this prospective observational study, we utilized time-resolved spectroscopy (TRS), in which the effect of extracranial contamination is thought to be minimal, and evaluated whether the same result was obtained. We measured the changes in ScO as well as the total cerebral hemoglobin concentration (tHb) after treatment with ephedrine or phenylephrine during laparoscopic surgery by using a tNIRS-1 (Hamamatsu Photonics, Hamamatsu, Japan), which is a commercial instrument utilizing TRS. Based on a mixed-effects model with random intercepts for ScO or tHb including mean blood pressure, the mean difference and 95% confidence interval were evaluated as well as the predicted mean difference and its confidence interval using the interquartile range of mean blood pressure. Fifty treatments with ephedrine or phenylephrine were done. The mean differences of ScO were less than 0.1% and the predicted mean differences were less than 1.1% for the two drugs. The mean differences of tHb were less than 0.02 μM and the predicted mean differences were less than 0.2 μM for the drugs. The changes in ScO and tHb after treatments with ephedrine and phenylephrine were very small and clinically insignificant when measured by TRS. Previous reports about phenylephrine may have been affected by extracranial contamination.
Topics: Humans; Phenylephrine; Ephedrine; Spectroscopy, Near-Infrared; Prospective Studies; Arterial Pressure; Oxygen
PubMed: 37243955
DOI: 10.1007/s10877-023-01036-y -
Journal of Pharmacy Practice Aug 2023During hospitalization, the risk of hypotension and associated sequelae remain important considerations for patient outcomes. The use of push-dose vasopressors (PDP)... (Review)
Review
During hospitalization, the risk of hypotension and associated sequelae remain important considerations for patient outcomes. The use of push-dose vasopressors (PDP) outside of the operating room has increased in recent years to combat the negative effects of hypotension. This narrative review evaluates the utility of PDP in its traditional perioperative setting as well as in areas of increasing use such as the emergency department and intensive care unit. Articles evaluating PDP highlight successful increases in blood pressure with all agents but differ in rates of adverse events and most lack direct comparison of PDP agents in regard to safety and efficacy. Agents utilized as PDP, including epinephrine, phenylephrine, norepinephrine, vasopressin, and ephedrine vary in mechanism of action, onset of action, and duration of action. These variations in pharmacology along with published literature may lead to differences in the preferred PDP for various clinical scenarios. Many adverse events associated with PDP have been due to dosing errors highlighting the importance of education surrounding the use of these agents. Additional research is necessary to further elucidate the risks and benefits of PDP in clinical practice, and to determine which PDP is truly preferred. Careful consideration should be given when determining the appropriateness of this administration method of vasopressors in various clinical scenarios.
Topics: Humans; Vasoconstrictor Agents; Phenylephrine; Epinephrine; Hypotension; Critical Care
PubMed: 35459405
DOI: 10.1177/08971900221096967 -
Experimental Physiology Dec 2023What is the central question of this study? What are the biggest challenges in performing in vitro studies on isolated human umbilical arteries? What is the main finding...
NEW FINDINGS
What is the central question of this study? What are the biggest challenges in performing in vitro studies on isolated human umbilical arteries? What is the main finding and its importance? The protocols presented in this study indicate some potential outcomes important for interpretation of the vascular responsivities of human umbilical arteries and could be useful for planning future in vitro studies with human umbilical arteries.
ABSTRACT
Human umbilical artery (HUA) preparations are of particular importance for in vitro studies on isolated blood vessels because their sampling is not risky for the patient, and they can provide the closest possible impression of changes related to the uteroplacental circulation during pre-eclampsia. Using organ bath techniques, useful experimental protocols are provided for measuring some pathophysiological phenomena in the vascular responses of HUAs. Several vasoconstrictors (serotonin, prostaglandin F and phenylephrine) and vasodilators (acetylcholine and minoxidil) were seleted for determination of their vasoactivity in HUAs. The role of L-type voltage-operated calcium channels and different types of potassium channels (K , BK and K ) were assessed, as was the impact of homocysteine. Serotonin was confirmed to be the most potent vasoconstrictor, while acetylcholine and phenylephrine caused variability in the relaxation and contraction response of HUA, respectively. The observed increase in serotonin-induced contraction and a decrease in minoxidil-induced relaxation in the presence of homocysteine suggested its procontractile effect on HUA preparations. Using selective blockers, it was determined that K and K channels participate in the minoxidil-induced relaxation, while L-type voltage-dependent Ca channels play an important role in the serotonin-induced contraction. The presented protocols reveal some of the methodological challenges related to HUA preparations and indicate potential outcomes in interpreting the vascular effects of the investigated substances, both in physiological conditions and in the homocysteine-induced pre-eclampsia model.
Topics: Pregnancy; Female; Humans; Umbilical Arteries; Serotonin; Acetylcholine; Minoxidil; Pre-Eclampsia; Vasodilation; Vasoconstrictor Agents; Phenylephrine; Homocysteine; Adenosine Triphosphate
PubMed: 37837634
DOI: 10.1113/EP091374 -
Scientific Reports Aug 2023The present work examined the effect of oral administration of rutin and its combination with metformin, an antidiabetic drug on blood glucose, total cholesterol and...
The present work examined the effect of oral administration of rutin and its combination with metformin, an antidiabetic drug on blood glucose, total cholesterol and triglycerides level and vascular function in streptozotocin (STZ) -induced diabetic rats. Male Sprague Dawley rats were rendered diabetic by a single intraperitoneal injection of STZ (50 mg/kg). Rutin and metformin were orally administered to diabetic rats at a dose of 100 mg/kg and 300 mg/kg body weight/day, respectively, for 4 weeks. Plasma analysis was conducted to determine changes in the plasma glucose and lipid levels. Rat aortic ring reactivity in response to endothelium-dependent (acetylcholine, ACh) and endothelium-independent (sodium nitroprusside, SNP) relaxants, and to the α1-adrenergic agonist phenylephrine (PE) were recorded. Histology of pancreas, liver and kidney were evaluated. In results, rutin and metformin alone and in combination has led to significant improvements in blood glucose, cholesterol and triglyceride levels compared to diabetic group. Diabetic aortic rings showed significantly greater contraction in response to PE, and less relaxation in response to ACh and SNP. Treatment with rutin and metformin in combination significantly reduced PE-induced contraction and increased ACh-induced and SNP-induced relaxation in diabetes when compared to rutin or metformin alone. Significant histological improvements were seen with combination therapy. In conclusion, rutin and metformin combination therapy has the most potentiality for restoring blood glucose and lipid level as well as vascular function.
Topics: Rats; Male; Animals; Metformin; Rats, Sprague-Dawley; Diabetes Mellitus, Type 1; Rutin; Diabetes Mellitus, Experimental; Blood Glucose; Phenylephrine; Acetylcholine; Cholesterol; Lipids; Endothelium, Vascular
PubMed: 37528147
DOI: 10.1038/s41598-023-39442-6 -
Clinical Autonomic Research : Official... Aug 2023Orthostatic hypotension is a common condition with heterogeneous and, in many cases, unclear underlying pathophysiology. Frequent symptoms are syncope and falls with a...
PURPOSE
Orthostatic hypotension is a common condition with heterogeneous and, in many cases, unclear underlying pathophysiology. Frequent symptoms are syncope and falls with a strong impact on daily life. A two-generation family with eight individuals segregating early-onset severe orthostatic hypotension with persistent tachycardia in upright position and repeated faints was identified. Our aim was to elucidate the underlying pathophysiology.
METHODS
One severely affected individual underwent thorough investigation with neurophysiological and blood pressure (BP) measurements, including direct recording of baroreflex-governed sympathetic nerve signalling and induction of BP rise with phenylephrine. Family members underwent parts of the examination. Genetic analysis using exome sequencing was performed.
RESULTS
Marked postural hypotension with greatly reduced cardiac preload was observed, but without signs of autonomic nervous system dysfunction: sympathetic nerve signalling was normal, as were catecholamine levels, and phenylephrine stimulation revealed a normal increase in BP. The results of the genetic analysis using exome sequencing comprising all known genes associated with the regulation of BP and catecholamine metabolism were normal.
CONCLUSION
The combined findings suggest an autosomal dominant form of early-onset orthostatic hypotension with variable clinical expression and without any additional autonomic dysfunction. It is possible that further investigation will reveal an as yet undescribed entity of orthostatic hypotension transmitted as an autosomal dominant trait.
Topics: Humans; Hypotension, Orthostatic; Sweden; Autonomic Nervous System Diseases; Syncope; Phenylephrine; Catecholamines
PubMed: 37460866
DOI: 10.1007/s10286-023-00963-9 -
Indian Journal of Ophthalmology Jul 2024To study the pupil dynamics with premixed intracameral anesthetic mydriatic combination of phenylephrine (0.31%), tropicamide (0.02%), and lidocaine (1%) in pediatric...
PURPOSE
To study the pupil dynamics with premixed intracameral anesthetic mydriatic combination of phenylephrine (0.31%), tropicamide (0.02%), and lidocaine (1%) in pediatric cataract surgery.
METHODS
Consecutive children aged ≤12 years planned for cataract surgery were recruited. A commercially available premixed combination of phenylephrine (0.31%), tropicamide (0.02%), and lidocaine (1%) was injected at the beginning of surgery without any topical/infusion drugs for mydriasis. Pupil sizes at various points of surgery were studied.
RESULTS
We recruited 75 patients with a mean age of 24.3 ± 33.4 months (range: 1 month-11 years). Adequate mydriasis with a single injection was achieved in 93.5% (n = 73 eyes of 70 patients) without additional pharmacotherapy or intervention. The mean pupillary diameter increased from 1.8 ± 0.79 to 6.1 ± 1.4 mm after injection (mean change of 4.2 ± 1.25 mm from baseline). The mean variability in pupillary diameter was 0.73 ± 1.3 mm. In five eyes, good dilatation was not possible even after repeat injection.
CONCLUSION
Fixed-dose premixed intracameral injection is effective in pupil dilatation. It alleviates the need for any topical dilators or additional intraoperative supplementation for pediatric cataract surgery.
Topics: Humans; Mydriatics; Child, Preschool; Male; Infant; Female; Cataract Extraction; Pupil; Child; Tropicamide; Phenylephrine; Lidocaine; Anterior Chamber; Cataract; Prospective Studies; Follow-Up Studies; Ophthalmic Solutions; Dose-Response Relationship, Drug
PubMed: 38454863
DOI: 10.4103/IJO.IJO_2628_23 -
Journal of Clinical Anesthesia Nov 2023Administering a 5-hydroxytryptamine-3 receptor (5-HT3) at anesthesia induction may aid in achieving hemodynamic stability during general anesthesia induced using... (Randomized Controlled Trial)
Randomized Controlled Trial
The preventive effect of 5-hydroxytryptamine-3 receptor antagonist on blood pressure reduction and postoperative nausea and vomiting during general anesthesia induction: A double-blinded, randomized controlled trial.
STUDY OBJECTIVE
Administering a 5-hydroxytryptamine-3 receptor (5-HT3) at anesthesia induction may aid in achieving hemodynamic stability during general anesthesia induced using opioids. Therefore, we aimed to evaluate the effect of ramosetron, a 5-HT3 antagonist, administered on hypotension at the induction of total intravenous anesthesia (TIVA) with propofol and remifentanil. Additionally, we aimed to compare the impact of ramosetron administration at anesthesia induction versus that at the end of the surgery on postoperative nausea and vomiting (PONV).
DESIGN
Patients were randomly allocated to the Induction group (administration of ramosetron [0.3 mg/5 ml] at anesthesia induction and normal saline [5 ml] at the end of the surgery) or End group (administration of normal saline [5 ml] at anesthesia induction and ramosetron [0.3 mg/5 ml] at the end of the surgery). Hemodynamic status, PONV, and postoperative pain were assessed.
SETTING
Operating room, post-anesthetic care unit, and general ward.
PATIENTS
In total, 176 non-smoking patients without any past medical history undergoing laparoscopic gynecological surgeries under TIVA were included in the study.
MEASUREMENTS
Blood pressure (BP), heart rate, PONV, visual analog scale (VAS).
MAIN RESULTS
The Induction group exhibited significantly higher BP at anesthesia induction and required significantly lower doses of phenylephrine and ephedrine during anesthesia than the End group had. However, PONV and postoperative pain were similar between the two groups.
CONCLUSIONS
Administering ramosetron at anesthesia induction resulted in significantly better hemodynamic stability with significantly lesser requirement of phenylephrine and ephedrine than administering at the end of the surgery did. Therefore, we recommend ramosetron administration at anesthesia induction rather than at the end of the surgery to prevent PONV and the decrease in the mean BP during TIVA with propofol and remifentanil.
Topics: Humans; Postoperative Nausea and Vomiting; Propofol; Blood Pressure; Ephedrine; Receptors, Serotonin, 5-HT3; Remifentanil; Saline Solution; Hypotension; Anesthesia, General; Phenylephrine; Pain, Postoperative
PubMed: 37633042
DOI: 10.1016/j.jclinane.2023.111232 -
BioRxiv : the Preprint Server For... Nov 2023During postnatal cardiac hypertrophy, cardiomyocytes undergo mitotic exit, relying on DNA replication-independent mechanisms of histone turnover to maintain chromatin...
During postnatal cardiac hypertrophy, cardiomyocytes undergo mitotic exit, relying on DNA replication-independent mechanisms of histone turnover to maintain chromatin organization and gene transcription. In other tissues, circadian oscillations in nucleosome occupancy influence clock-controlled gene expression, suggesting an unrecognized role for the circadian clock in temporal control of histone turnover and coordinate cardiomyocyte gene expression. To elucidate roles for the master circadian transcription factor, Bmal1, in histone turnover, chromatin organization, and myocyte-specific gene expression and cell growth in the neonatal period. Bmal1 knockdown in neonatal rat ventricular myocytes (NRVM) decreased myocyte size, total cellular protein, and transcription of the fetal hypertrophic gene Nppb following treatment with increasing serum concentrations or the α-adrenergic agonist phenylephrine (PE). Bmal1 knockdown decreased expression of clock-controlled genes Per2 and Tcap, and salt-inducible kinase 1 (Sik1) which was identified via gene ontology analysis of Bmal1 targets upregulated in adult versus embryonic hearts. Epigenomic analyses revealed co-localized chromatin accessibility and Bmal1 localization in the Sik1 promoter. Bmal1 knockdown impaired Per2 and Sik1 promoter accessibility as measured by MNase-qPCR and impaired histone turnover indicated by metabolic labeling of acid-soluble chromatin fractions and immunoblots of total and chromatin-associated core histones. Sik1 knockdown basally increased myocyte size, while simultaneously impairing and driving Nppb and Per2 transcription, respectively. Bmal1 is required for neonatal myocyte growth, replication-independent histone turnover, and chromatin organization at the Sik1 promoter. Sik1 represents a novel clock-controlled gene that coordinates myocyte growth with hypertrophic and clock-controlled gene transcription.
PubMed: 38014083
DOI: 10.1101/2023.11.14.567086 -
Biomedicine & Pharmacotherapy =... Sep 2023Left ventricular hypertrophy leads to heart failure, a serious medical condition associated with high rates of hospitalization and mortality. Limited success with the...
Left ventricular hypertrophy leads to heart failure, a serious medical condition associated with high rates of hospitalization and mortality. Limited success with the existing pharmacological treatments necessitates the development of mechanisms-based new therapies to better control the progression from left ventricular hypertrophy to heart failure. The current work investigated the pharmacological potentials and mechanisms of naturally occurring cinnamic acid in the treatment of left ventricular hypertrophy and heart failure. The in vitro findings reveal that cinnamic acid attenuates the hypertrophic responses and mitochondrial dysfunction in the phenylephrine (PE)-stimulated cardiomyocytes. Furthermore, cinnamic acid offsets PE-induced increases in N-methyladenosine (mA) RNA modification and reductions in the expression of the key mA demethylase FTO in cardiomyocytes. Most importantly, FTO knockdown abrogates anti-hypertrophic and mitochondrial protective effects of cinnamic acid in the PE-stimulated cardiomyocytes. The in vivo results further demonstrate that cinnamic acid mitigates left ventricular hypertrophy, left ventricular systolic dysfunction and ultrastructural impairment of cardiomyocyte mitochondria and myofibrils in the mice subjected to transverse aortic constriction (TAC)-induced pressure overload. Moreover, FTO knockdown abolishes these beneficial effects of cinnamic acid in the TAC mice. In conclusion, the work here demonstrates for the first time that cinnamic acid is effective at mitigating pressure overload-induced left ventricular hypertrophy and heart failure in part by modulating the expression of FTO and the level of FTO-dependent mA RNA modification in cardiomyocytes. These novel findings warrant further evaluation of cinnamic acid as a pharmacological agent/component to complement the existing treatment of pressure overload-mediated left ventricular hypertrophy and heart failure.
Topics: Mice; Animals; Hypertrophy, Left Ventricular; Myocytes, Cardiac; Heart Failure; Phenylephrine; RNA; Mice, Inbred C57BL; Disease Models, Animal; Alpha-Ketoglutarate-Dependent Dioxygenase FTO
PubMed: 37453198
DOI: 10.1016/j.biopha.2023.115168