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The American Journal of Emergency... Dec 2023Hypotension is a common problem in the emergency department (ED) and intensive care unit (ICU) and can increase risk for poor outcomes. Many EDs/ICUs utilize epinephrine...
BACKGROUND
Hypotension is a common problem in the emergency department (ED) and intensive care unit (ICU) and can increase risk for poor outcomes. Many EDs/ICUs utilize epinephrine and phenylephrine to treat hypotension and these medications are most often administered as a continuous infusion (CI). Push-dose (PD) is the administration of small medication doses as intermittent intravenous pushes (IVPs). There is limited information comparing the time required to prepare and administer PD versus CI and errors have been reported when preparing and administering these medications at bedside. This simulation study sought to estimate preparation and administration times and preparation and errors with PD and CI epinephrine and phenylephrine when prepared by an ED/ICU pharmacist.
METHODS
This crossover simulation study took place in a simulation center at an academic medical center and utilized a multi-venous intravenous training arm kit equip with an 18-gauge intravenous line, an extension tubing set, and a luer-lock adapter. The primary outcome was total preparation and administration time in seconds. The secondary outcome was major preparation and administration errors, defined as errors causing a five-fold or greater overdose.
RESULTS
In total, 16 pharmacists participated, including nine ED and seven ICU pharmacists. PD had faster total preparation and administration time and administration time, but not preparation time; PD showed an approximate 70 s decrease in total preparation and administration time versus CI. PD had more major preparation and administration errors and six PD preparations (18.8%, 6/32) had at least one major preparation and administration error. CI, on the other hand, had no major preparation and administration errors.
DISCUSSION
This simulation found faster total preparation and administration time with PD versus CI epinephrine and phenylephrine, but also found that PD had more major preparation and administration errors. Dilutional errors during medication preparation were the cause of 83.3% (5/6) of our overdoses.
CONCLUSION
This simulation study showed that ED/ICU pharmacists had faster median total preparation and administration times for PD epinephrine and phenylephrine versus CI, but PD also had more preparation and administration errors.
Topics: Humans; Phenylephrine; Medication Errors; Epinephrine; Infusions, Intravenous; Hypotension
PubMed: 37832396
DOI: 10.1016/j.ajem.2023.10.002 -
Journal of AAPOS : the Official... Feb 2019To examine the cycloplegic and mydriatic effect of tropicamide omission from a common pediatric eye drop combination.
PURPOSE
To examine the cycloplegic and mydriatic effect of tropicamide omission from a common pediatric eye drop combination.
METHODS
Consecutive children examined at the Ann & Robert H. Lurie Children's Hospital of Chicago from June 8, 2017 to September 6, 2017 were enrolled prospectively. Tropicamide, cyclopentolate, and phenylephrine (TCP) was instilled in one eye; cyclopentolate and phenylephrine (CP), in the other. Spherical equivalent, maximum pupil size, and pupillary constriction in response to photostimulation were measured before and 30 minutes after instillation using an autorefractor and pupillometer. Iris pigmentation was examined as a between-subjects variable.
RESULTS
A total of 75 children 4-11 years of age were included. Mean differences in spherical equivalent between TCP and CP were not statistically significant (P = 0.95). Significant interactions between eye drop regimen and iris pigmentation were observed for pupil size (P = 0.001) and constriction percentage (P = 0.02). Among only patients with dark irides, TCP yielded slightly larger pupils (7.70 vs 7.31 mm [P < 0.001]) that were less responsive to light (5.75% vs 8.07% [P = 0.002]). All pupils dilated to ≥6.0 mm, with equivalent proportions achieving ≥7.0 mm for TCP and CP (P = 0.18).
CONCLUSIONS
TCP and CP elicited equivalent cycloplegic effects. Mydriatic differences between the regimens, although statistically significant in dark irides, were of limited clinical magnitude, and all pupils achieved sufficient dilation for funduscopy.
Topics: Child; Child, Preschool; Cyclopentolate; Drug Therapy, Combination; Female; Humans; Male; Mydriasis; Mydriatics; Phenylephrine; Prospective Studies; Treatment Outcome; Tropicamide
PubMed: 30641136
DOI: 10.1016/j.jaapos.2018.08.012 -
BMC Complementary Medicine and Therapies Apr 2022Trans-cinnamaldehyde (TCA) is one of the main pharmaceutical ingredients of Cinnamomum cassia Presl, which has been shown to have therapeutic effects on a variety of...
BACKGROUND
Trans-cinnamaldehyde (TCA) is one of the main pharmaceutical ingredients of Cinnamomum cassia Presl, which has been shown to have therapeutic effects on a variety of cardiovascular diseases. This study was carried out to characterize and reveal the underlying mechanisms of the protective effects of TCA against cardiac hypertrophy.
METHODS
We used phenylephrine (PE) to induce cardiac hypertrophy and treated with TCA in vivo and in vitro. In neonatal rat cardiomyocytes (NRCMs), RNA sequencing and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were carried out to identify potential pathways of TCA. Then, the phosphorylation and nuclear localization of calcium/calmodulin-dependent protein kinase II (CaMKII) and extracellular signal-related kinase (ERK) were detected. In adult mouse cardiomyocytes (AMCMs), calcium transients, calcium sparks, sarcomere shortening and the phosphorylation of several key proteins for calcium handling were evaluated. For mouse in vivo experiments, cardiac hypertrophy was evaluated by assessing morphological changes, echocardiographic parameters, and the expression of hypertrophic genes and proteins.
RESULTS
TCA suppressed PE-induced cardiac hypertrophy and the phosphorylation and nuclear localization of CaMKII and ERK in NRCMs. Our data also demonstrate that TCA blocked the hyperphosphorylation of ryanodine receptor type 2 (RyR2) and phospholamban (PLN) and restored Ca handling and sarcomere shortening in AMCMs. Moreover, our data revealed that TCA alleviated PE-induced cardiac hypertrophy in adult mice and downregulated the phosphorylation of CaMKII and ERK.
CONCLUSION
TCA has a protective effect against PE-induced cardiac hypertrophy that may be associated with the inhibition of the CaMKII/ERK pathway.
Topics: Acrolein; Animals; Calcium; Calcium-Calmodulin-Dependent Protein Kinase Type 2; Cardiomegaly; MAP Kinase Signaling System; Mice; Myocytes, Cardiac; Phenylephrine; Rats; Ryanodine Receptor Calcium Release Channel
PubMed: 35468773
DOI: 10.1186/s12906-022-03594-1 -
BMC Pediatrics Nov 2019To determine effects and side effects of topical application of phenylephrine 2.5% and tropicamide 0.5% combination in preterm infants. (Observational Study)
Observational Study
BACKGROUND
To determine effects and side effects of topical application of phenylephrine 2.5% and tropicamide 0.5% combination in preterm infants.
METHODS
In this prospective observational study, 60 infants undergoing retinopathy of prematurity (ROP) screening were prospectively observed. Pupillary diameter, blood pressure, heart rate, and oxygen saturation were monitored before and after up to 24 h during ROP screening examinations.
RESULTS
The mean pupillary diameter 1 h after the instillation of drops was 5.58 ± 0.75 mm for both eyes. The mean systolic and diastolic pressure and oxygen saturation of infants did not change statistically until the end of the study. The average heart rate decreased by a mean of 4.96 beats/minute from the baseline following eye drops instillation. General condition deterioration, fall in oxygen saturation and bradycardia were observed in 4 infants that already had respiratory distress syndrome.
CONCLUSION
The phenylephrine 2.5% plus tropicamide 0.5% drop is effective and safe as mydriatic combination for retinopathy of prematurity screening. In infants with an additional systemic disease such as respiratory distress syndrome, the side effects of mydriatic drops may be more common. Such babies should be kept under close observation.
TRIAL REGISTRATION
The trial was retrospectively registered on 28 February 2018. The ClinicalTrials.gov Identifier is NCT03448640.
Topics: Blood Pressure; Drug Therapy, Combination; Gestational Age; Humans; Infant, Newborn; Infant, Premature; Mydriatics; Myocardial Contraction; Oxygen; Phenylephrine; Prospective Studies; Retinopathy of Prematurity; Tropicamide
PubMed: 31690284
DOI: 10.1186/s12887-019-1757-3 -
European Journal of Pharmacology Jul 2023A role for mitochondrial fission in vascular contraction has been proposed based on the vasorelaxant activity of the dynamin (and mitochondrial fission) inhibitors...
A role for mitochondrial fission in vascular contraction has been proposed based on the vasorelaxant activity of the dynamin (and mitochondrial fission) inhibitors mdivi-1 and dynasore. However, mdivi-1 is capable to inhibit Ba currents through Ca1.2 channels (I), stimulate K1.1 channel currents (I), and modulate pathways key to the maintenance of vessel active tone in a dynamin-independent manner. Using a multidisciplinary approach, the present study demonstrates that dynasore, like mdivi-1, is a bi-functional vasodilator, blocking I and stimulating I in rat tail artery myocytes, as well as promoting relaxation of rat aorta rings pre-contracted by either high K or phenylephrine. Conversely, its analogue dyngo-4a, though inhibiting mitochondrial fission triggered by phenylephrine and stimulating I, did not affect I but potentiated both high K- and phenylephrine-induced contractions. Docking and molecular dynamics simulations identified the molecular basis supporting the different activity of dynasore and dyngo-4a at Ca1.2 and K1.1 channels. Mito-tempol only partially counteracted the effects of dynasore and dyngo-4a on phenylephrine-induced tone. In conclusion, the present data, along with previous observations (Ahmed et al., 2022) rise caution for the use of dynasore, mdivi-1, and dyngo-4a as tools to investigate the role of mitochondrial fission in vascular contraction: to this end, a selective dynamin inhibitor and/or a different experimental approach are needed.
Topics: Rats; Animals; Mitochondrial Dynamics; Dynamins; Niacinamide; Phenylephrine
PubMed: 37179045
DOI: 10.1016/j.ejphar.2023.175786 -
Journal of Cardiac Failure May 2022To assess the relationships between Valsalva- and phenylephrine test-derived measures and outcome in patients with heart failure with reduced ejection fraction (HFrEF)... (Clinical Trial)
Clinical Trial
Valsalva-derived Measures and Phenylephrine Test in Patients With Heart Failure With Reduced Ejection Fraction Receiving Comprehensive Neurohormonal Blockade Drug Therapy: A 5-year Event-free Survival Analysis.
BACKGROUND
To assess the relationships between Valsalva- and phenylephrine test-derived measures and outcome in patients with heart failure with reduced ejection fraction (HFrEF) receiving comprehensive neurohormonal blockade pharmacotherapy.
METHODS AND RESULTS
Data from 56 patients with HFrEF (mean left ventricle ejection fraction of 32 ± 6%) subjected to Valsalva and phenylephrine tests were analyzed retrospectively. Baroreflex-related (Valsalva-ratio and blood pressure-RR interval slope from phase IV) and non-baroreflex-related measures (systolic blood pressure rise in phase IV [ΔSBP], and pulse amplitude ratio [PAR]) were calculated from Valsalva. Short-term outcomes (HF-related hospitalization, implantable cardioverter-defibrillator shock or all-cause death within 24 months from examination) and long-term outcomes (implantable cardioverter-defibrillator shock or all-cause death within 60 months) were analyzed. The end point occurred in 16 and 18 patients, for the short- and long-term outcomes, respectively. A low ΔSBP identified patients at risk in the long term, as evidenced by a low vs high ΔSBP comparison (square-wave response patients assigned to low ΔSBP group, P = .002), and Cox model (hazard ratio 0.91, 95% confidence interval 0.86-0.96, P < .001), and tended to identify patients at risk in the short term outcome (hazard ratio 0.95, 95% confidence interval 0.91-1.00, P = .055). There was a tendency toward a higher event-free survival in the low PAR group (low vs high PAR; hazard ratio 0.44, 95% CI 0.17-1.18, P = .104).
CONCLUSIONS
Non-baroreflex-related measures obtained from Valsalva-namely, ΔSBP and PAR-might carry prognostic value in patients with HFrEF receiving neurohormonal blockade pharmacotherapy.
Topics: Heart Failure; Humans; Phenylephrine; Progression-Free Survival; Retrospective Studies; Stroke Volume; Ventricular Dysfunction, Left
PubMed: 34758387
DOI: 10.1016/j.cardfail.2021.10.012 -
Journal of Ocular Pharmacology and... Jun 2020Mixed eye drops containing 0.5% tropicamide and 0.5% phenylephrine are commercially available for cycloplegic refraction. Determining the pharmacokinetics (PK) and... (Comparative Study)
Comparative Study
Mixed eye drops containing 0.5% tropicamide and 0.5% phenylephrine are commercially available for cycloplegic refraction. Determining the pharmacokinetics (PK) and distribution of tropicamide and phenylephrine simultaneously in ocular tissues is an important but challenging issue. Herein, we developed a sensitive and selective ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method for simultaneous determination of tropicamide and phenylephrine concentrations in rabbit ocular tissues and plasma. The two analytes were extracted with ethyl acetate using etofesalamide as an internal standard and separated using a chromatographic C column with isocratic elution. Mass spectrometry analysis was performed with positive electrospray ionization and data were acquired in a multiple reaction monitoring mode. We validated this method over a concentration range of 5-1,600 ng/mL for tropicamide and 1-320 ng/mL for phenylephrine in ocular tissues, as well as 0.5-64 ng/mL for both compounds in plasma. Inter- and intraday precisions in all samples were both <12.9% and the accuracy was within 92.1%-108.4%. The highest concentration of tropicamide was found in aqueous humor (C: 29430 ng/g), while was in cornea for phenylephrine (C: 3465 ng/g). All the ocular tissues concentrations were much higher than those of blood. This UPLC-MS/MS method allowed us to determine the PK and distribution of tropicamide and phenylephrine in rabbit ocular tissue, which may be helpful in the future development and application of mydriatic agents.
Topics: Administration, Topical; Adrenergic alpha-1 Receptor Agonists; Animals; Aqueous Humor; Chromatography, Liquid; Cornea; Eye; Mydriatics; Ophthalmic Solutions; Phenylephrine; Plasma; Rabbits; Reproducibility of Results; Tandem Mass Spectrometry; Tropicamide
PubMed: 32320311
DOI: 10.1089/jop.2019.0152 -
The Safety and Efficacy of Peripherally Administered Norepinephrine during the Perioperative Period.AANA Journal Oct 2022Intraoperative hypotension (IOH) is a highly prevalent adverse event associated with the induction and maintenance of general anesthesia. While the etiology of IOH is...
Intraoperative hypotension (IOH) is a highly prevalent adverse event associated with the induction and maintenance of general anesthesia. While the etiology of IOH is complex and multifactorial, hypotension most often occurs because anesthetic agents decrease vascular smooth muscle tone, impair myocardial contractility, and decrease levels of circulating catecholamines. The vasopressor drugs phenylephrine, norepinephrine (NE), and ephedrine have been traditionally used to counteract anesthesia-induced hypotension, with the sympathomimetic agent phenylephrine historically viewed as the first-line agent. However, NE may have a more advantageous clinical profile for treating hypotension by maintaining or increasing cardiac output and restoring decreased concentrations of circulating catecholamines. Yet despite these advantages, concerns of the safety of peripherally administered NE have limited its use to specific clinical settings such as central line in situ. Recent bench and clinical research examining the efficacy and safety profile of peripherally administered NE indicates that this stigma bears reexamination. Data from human and animal studies suggest that the peripheral administration of NE for the treatment of IOH may not only be acceptable, but in many cases, may be the best option.
Topics: Animals; Ephedrine; Humans; Hypotension; Norepinephrine; Perioperative Period; Phenylephrine; Sympathomimetics
PubMed: 36173798
DOI: No ID Found -
European Journal of Anaesthesiology Jul 2022
Topics: Humans; Hypotension; Norepinephrine; Phenylephrine; Vasoconstrictor Agents
PubMed: 35759290
DOI: 10.1097/EJA.0000000000001697 -
Drug Design, Development and Therapy 2022Norepinephrine has been associated with improved heart rate (HR) and cardiac output (CO) compared to phenylephrine as a treatment for post-spinal hypotension during... (Randomized Controlled Trial)
Randomized Controlled Trial
Comparison of Prophylactic Norepinephrine and Phenylephrine Infusions During Spinal Anaesthesia for Primary Caesarean Delivery in Twin Pregnancies: A Randomized Double-Blinded Clinical Study.
BACKGROUND
Norepinephrine has been associated with improved heart rate (HR) and cardiac output (CO) compared to phenylephrine as a treatment for post-spinal hypotension during caesarean delivery (CD) in singleton pregnancies. Our current study compared the effects of norepinephrine and phenylephrine in maintaining maternal hemodynamics after spinal anaesthesia in twin pregnancies during elective CD.
METHODS
This was a double-blinded, randomized, controlled study. From December 2017 to December 2018, 62 women with healthy twin term pregnancies undergoing elective CD under spinal anaesthesia were studied. Following spinal induction, either norepinephrine (6 μg/mL) or phenylepinephrine (75 μg/mL) was infused at 60 mL/h to maintain systolic blood pressure (SBP) near baseline until delivery. HR, SBP, systemic vascular resistance (SVR), and CO were collected using anaesthesia monitors and continuous-pulse waveform analysis. The primary outcome was maternal CO. Other parameters of maternal hemodynamics, umbilical cord blood gases, and adverse events were also compared.
RESULTS
Hemodynamic variables (CO, SBP, HR, and SVR) between spinal anaesthesia induction to skin incision were similar between the two groups ( = 0.889, 0.057, 0.977, and 0.416, respectively). The incidence of bradycardia was significantly higher in the phenylephrine group (69%) than in the norepinephrine group (24.2%, <0.001). Maternal nausea and vomiting, hypotension, reactive hypertension, and neonatal outcomes did not differ between the groups.
CONCLUSION
When administered as a prophylactic fixed-rate infusion, phenylephrine and norepinephrine are both capable of maintaining maternal blood pressure following spinal anaesthesia in twin pregnancies. There were no differences in the maternal hemodynamics or foetal outcomes between women receiving norepinephrine and phenylephrine.
PREVIOUS PRESENTATIONS
Presented at the 51st Society for Obstetric Anesthesia and Perinatology Annual Meeting, Phoenix, Arizona, May 1-5, 2019.
CLINICAL TRIAL NUMBER AND REGISTRY
No. ChiCTR-IOR-17013358.
Topics: Anesthesia, Spinal; Cesarean Section; Female; Humans; Infant, Newborn; Norepinephrine; Phenylephrine; Pregnancy; Pregnancy, Twin; Vasoconstrictor Agents
PubMed: 35355656
DOI: 10.2147/DDDT.S357507