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International Journal of Obstetric... May 2024Hypotension is common during spinal anesthesia for cesarean delivery. Preventive strategies include fluid loading and phenylephrine. We hypothesized that if prophylactic... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Hypotension is common during spinal anesthesia for cesarean delivery. Preventive strategies include fluid loading and phenylephrine. We hypothesized that if prophylactic phenylephrine infusion is used, omission of fluid loading would be non-inferior to fluid co-loading in maintaining cardiac output. We assumed that if there was a difference, the increase in cardiac output would be greater in the no-loading than in the co-loading group.
METHODS
Term pregnant women scheduled for elective cesarean delivery were randomized to receive 1 L crystalloid co-loading or maintenance fluids only. Phenylephrine was titrated to maintain blood pressure. Changes in cardiac output following spinal anesthesia were the primary outcome. The study was powered as a non-inferiority trial, allowing the no-loading arm to have a 50% greater change in cardiac output. Heart rate, dose of phenylephrine, occurrence of nausea and vomiting, Apgar scores and neonatal acid base status were secondary outcomes.
RESULTS
Data from 63 women were analyzed. In contrast to our hypothesis, there was 33% less increase in cardiac output with no loading (ratio 0.67, 95% CI 0.15 to 1.36), and 60% greater reduction of cardiac output with no loading (ratio 1.6, 95% CI 1.0 to 2.7). Total dose of phenylephrine was higher in the no-loading group. There may be a less favorable neonatal acid base status without volume loading.
CONCLUSION
Omission of crystalloid co-loading leads to a decrease in cardiac output which has a potentially unfavorable impact on neonatal acid base status. We conclude that crystalloid co-loading may be useful in the presence of phenylephrine infusion.
Topics: Humans; Female; Cesarean Section; Pregnancy; Crystalloid Solutions; Double-Blind Method; Hypotension; Adult; Anesthesia, Spinal; Phenylephrine; Anesthesia, Obstetrical; Elective Surgical Procedures; Cardiac Output; Vasoconstrictor Agents
PubMed: 38485584
DOI: 10.1016/j.ijoa.2023.103968 -
Drug Design, Development and Therapy 2024Norepinephrine has fewer negative effects on heart rate (HR) and cardiac output (CO) for treating postspinal hypotension (PSH) compared with phenylephrine during... (Randomized Controlled Trial)
Randomized Controlled Trial Clinical Trial
Randomized Double-Blinded Comparison of Intermittent Boluses Phenylephrine and Norepinephrine for the Treatment of Postspinal Hypotension in Patients with Severe Pre-Eclampsia During Cesarean Section.
BACKGROUND
Norepinephrine has fewer negative effects on heart rate (HR) and cardiac output (CO) for treating postspinal hypotension (PSH) compared with phenylephrine during cesarean section. However, it remains unclear whether fetuses from patients with severe pre-eclampsia could benefit from the superiority of CO. The objective of this study was to compare the safety and efficacy of intermittent intravenous boluses of phenylephrine and norepinephrine used in equipotent doses for treating postspinal hypotension in patients with severe pre-eclampsia during cesarean section.
METHODS
A total of 80 patients with severe pre-eclampsia who developed PSH predelivery during cesarean section were included. Eligible patients were randomized at a 1:1 ratio to receive either phenylephrine or norepinephrine for treating PSH. The primary outcome was umbilical arterial pH. Secondary outcomes included other umbilical cord blood gas values, Apgar scores at 1 and 5 min, changes in hemodynamic parameters including CO, mean arterial pressure (MAP), HR, stroke volume (SV), and systemic vascular resistance (SVR), the number of vasopressor boluses required, and the incidence of bradycardia, hypertension, nausea, vomiting, and dizziness.
RESULTS
No significant difference was observed in umbilical arterial pH between the phenylephrine and norepinephrine groups (7.303±0.38 vs 7.303±0.44, respectively; P=0.978). Compared with the phenylephrine group, the overall CO (P=0.009) and HR (P=0.015) were greater in the norepinephrine group. The median [IQR] total number of vasopressor boluses required was comparable between the two groups (2 [1 to 3] and 2 [1 to 3], respectively; P=0.942). No significant difference was found in Apgar scores or the incidence of maternal complications between groups.
CONCLUSION
A 60 µg bolus of phenylephrine and a 4.5 µg bolus of norepinephrine showed similar neonatal outcomes assessed by umbilical arterial pH and were equally effective when treating PSH during cesarean section in patients with severe pre-eclampsia. Norepinephrine provided a higher maternal CO and a lower incidence of bradycardia.
Topics: Female; Humans; Infant, Newborn; Pregnancy; Anesthesia, Spinal; Bradycardia; Cesarean Section; Double-Blind Method; Hypotension; Norepinephrine; Phenylephrine; Pre-Eclampsia; Vasoconstrictor Agents
PubMed: 38476203
DOI: 10.2147/DDDT.S446657 -
Cureus Feb 2024Vasoplegia, the demonstration of persistently low systemic vascular resistance (SVR) and resistant hypotension in the presence of a normal cardiac index despite...
The Use of Methylene Blue in Conjunction With Hydroxocobalamin and Multiple Pressors to Treat Severe Vasoplegia in a Patient Due to Calcium Channel Blocker Toxicity: A Case Report.
Vasoplegia, the demonstration of persistently low systemic vascular resistance (SVR) and resistant hypotension in the presence of a normal cardiac index despite aggressive resuscitation attempts, is a serious clinical diagnosis that requires prompt treatment to prevent patient morbidity and mortality. Currently, treatment of vasoplegia involves treatment with vasopressors such as vasopressin, norepinephrine, and hydroxocobalamin. However, some evidence suggests that in addition to this treatment regimen, the addition of methylene blue may result in a reduction in overall norepinephrine equivalent vasopressor requirements, increased mean arterial pressure, and an improved clinical course. Here, we report the case of a 64-year-old male patient who presented to the ED after being found unresponsive and covered in emesis at home. The patient's presentation was complicated by worsening dyspnea, hypotension, and hemodynamic instability, requiring intubation and admission to the ICU for management of undifferentiated shock of unclear etiology and acute respiratory failure. Urine studies were consistent with a diagnosis of vasoplegia due to dihydropyridine calcium channel blocker toxicity, which was confirmed by pill counting of his home medications in the setting of recent paranoia and depression. The patient was treated aggressively with vasopressors, including vasopressin, phenylephrine, and epinephrine, as well as a combination of hydroxocobalamin and methylene blue. He was also started on a calcium and insulin drip. Upon initiation of non-catecholamine agents for vasoplegia, his clinical course quickly improved, and he was weaned from all vasopressors. He regained hemodynamic stability, was successfully extubated, evaluated by psychiatry, and discharged from the hospital in a stable condition on day 15 with the continuation of outpatient psychiatric services.
PubMed: 38465145
DOI: 10.7759/cureus.53778 -
International Neurourology Journal Feb 2024Adreno-muscarinic synergy, a supra-additional contractile response to simultaneous application of α-adrenoreceptor and muscarinic receptor agonists, is a feature of...
PURPOSE
Adreno-muscarinic synergy, a supra-additional contractile response to simultaneous application of α-adrenoreceptor and muscarinic receptor agonists, is a feature of several lower urinary tract regions that have dual sympathetic and parasympathetic innervation. We tested the hypothesis that synergy is also a feature of prostate tissue obtained from men with benign prostatic enlargement.
METHODS
Isolated tissue strips were dissected from prostate 'chips', collected after transurethral prostate resection procedures for in vitro experiments, to measure isometric tension at 36°C.
RESULTS
Added separately to the superfusate, phenylephrine and carbachol generated contractions with mean pEC50 (-log10EC50) values of 5.36 and 5.58, respectively, although phenylephrine maximal responses were about six-fold greater. In the presence of carbachol, the mean phenylephrine pEC50 was significantly increased to 5.84 and maximal response increased by 28%; overall, a significant synergistic response was demonstrated. The synergistic response was reduced by muscarinic receptor antagonists, most potently by the M3-selective agent 4-DAMP (1,1-dimethyl-4-diphenylacetoxypiperidinium iodide), and less so by M2 and M1-selective inhibitors gallamine and pirenzepine, but with an overall profile indicating M3/M2 mediation of the synergistic response. The magnitude of the synergistic response was variable between prostate chips that provided isolated preparations suggesting regional heterogenicity, although their zonal origin could not be determined.
CONCLUSION
These experiments show that adreno-muscarinic contractile synergy is a feature of human hyperplastic prostate tissue. This has implications for the use of a combination therapy of α-blockers and anti-muscarinic agent to relieve secondary symptoms associated with benign prostatic hyperplasia, at least in men who can tolerate antimuscarinics without a risk of retention.
PubMed: 38461856
DOI: 10.5213/inj.2346144.122 -
Annals of Anatomy = Anatomischer... Jun 2024A reliable estimation of time since death can be important for the law enforcement authorities. The compound method encompassing supravital reactions such as the...
BACKGROUND
A reliable estimation of time since death can be important for the law enforcement authorities. The compound method encompassing supravital reactions such as the chemical excitability of the iris can be used to further narrow intervals estimated by temperature-based methods. Postmortem iris excitability was mostly assessed by parasympatholytic or parasympathomimetic substances. Little is known regarding sympathomimetic agents. The present study aims to describe the postmortem iris excitability using the sympathomimetic drug phenylephrine.
METHODS
Cadavers were included after body donors gave written informed consent during lifetime. Exclusion criteria were known eye disease, or a postmortem interval exceeding 26 hours. A pupillometer with a minimum measurement range of 0.5 mm was used to determine the horizontal pupil diameter before and 20 minutes after the application of phenylephrine. Increase in pupil diameter was labeled as positive reaction, unchanged pupil diameter was labeled as negative reaction, and decrease in pupil diameter was labeled as paradox reaction.
RESULTS
30 eyes from 16 cadavers (median age = 80.0; 9 males, 7 females) were examined. Initial pupil size was in median 3.5 mm (interquartile range [IQR]: 3.0-4.5 mm) and progressed to 4.0 mm (IQR: 3.5-5.0 mm) 20 minutes after drug instillation. The achieved pupil diameter difference comprised in median 0.5 mm (IQR: 0.0-1.0 mm). A positive reaction was observed in 21 cases. Negative reactions were observed in 5 cases and paradox reactions in 4 cases. Overall, there was a statistically significant difference in diameter between the initial and the reactive pupil (P = 0.0002).
CONCLUSION
Although relatively rarely used, sympathomimetic drugs seem to be eligible for chemical postmortem iris excitability. Currently, assessment of postmortem iris excitability usually only involves parasympatholytic and parasympathomimetic agents. The findings of the present study give a hint that the application of a third agent with a sympathomimetic mechanism of action could provide additional information. Further studies assessing such a triple approach in the compound method in comparison with the current gold standard for estimation of time since death are mandatory to ensure reliable results.
Topics: Humans; Male; Female; Iris; Phenylephrine; Postmortem Changes; Pupil; Aged, 80 and over; Cadaver; Aged; Sympathomimetics
PubMed: 38460860
DOI: 10.1016/j.aanat.2024.152240 -
Experimental Physiology Jun 2024We sought to investigate possible impaired hyperaemia during dynamic handgrip exercise (HGE) in young healthy individuals who had recovered from COVID-19. We tested the...
We sought to investigate possible impaired hyperaemia during dynamic handgrip exercise (HGE) in young healthy individuals who had recovered from COVID-19. We tested the vascular function in individuals recovered from COVID-19 using a nitric oxide donor (i.e., sodium nitroprusside; SNP), which could revert a possible impaired endothelial function during HGE. Further, we tested whether individuals who recovered from COVID-19 would present exaggerated brachial vascular resistance under an adrenergic agonist (i.e., phenylephrine; PHE) stimuli during HGE. Participants were distributed into two groups: healthy controls (Control; men: n = 6, 30 ± 3 years, 26 ± 1 kg/m; and women: n = 5, 25 ± 1 years, 25 ± 1 kg/m) and subjects recovered from COVID-19 (post-COVID; men: n = 6, 29 ± 3 years, 25 ± 1 kg/m; and women: n = 10, 32 ± 4 years, 22 ± 1 kg/m). Participants in the post-COVID group tested positive (RT-PCR) 12-14 weeks before the protocol. Heart rate (HR), brachial blood pressure (BP), brachial blood flow (BBF) and vascular conductance (BVC) at rest were not different between groups. The HGE increased HR (Control: Δ9 ± 0.4 bpm; and post-COVID: Δ11 ± 0.4 bpm) and BP (Control: Δ6 ± 1 mmHg; and post-COVID: Δ12 ± 0.6 mmHg) in both groups. Likewise, BBF (Control: Δ632 ± 38 ml/min; and post-COVID: Δ620 ± 27 ml/min) and BVC (Control: Δ6.6 ± 0.4 ml/min/mmHg; and post-COVID: Δ6.1 ± 0.3 ml/min/mmHg) increased during HGE. SNP did not change HGE-induced hyperaemia but did decrease BP, which induced a reflex-related increase in HR. PHE infusion also did not change the HGE-induced hyperaemia but raised BP and reduced HR. In conclusion, exercise-induced hyperaemia is preserved in healthy young subjects 12-14 weeks after recovery from COVID-19 infection.
Topics: Humans; COVID-19; Male; Female; Hand Strength; Hyperemia; Adult; Exercise; Vascular Resistance; Heart Rate; Nitroprusside; Blood Pressure; Phenylephrine; SARS-CoV-2; Brachial Artery; Healthy Volunteers
PubMed: 38460126
DOI: 10.1113/EP091656 -
Medicine Mar 2024Phenylephrine may cause a reduction in maternal cerebral tissue oxygen saturation (SctO2) during Caesarean birth to prevent spinal hypotension; however, the effect of... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Phenylephrine may cause a reduction in maternal cerebral tissue oxygen saturation (SctO2) during Caesarean birth to prevent spinal hypotension; however, the effect of norepinephrine has not been assessed. We hypothesized that norepinephrine was more effective than phenylephrine in maintaining SctO2 when preventing spinal hypotension during Caesarean birth.
METHODS
We conducted a randomized, double-blind, controlled study. Sixty patients were randomly assigned to prophylactic norepinephrine or phenylephrine to maintain blood pressure during spinal anesthesia for Caesarean birth. SctO2, systolic blood pressure, and heart rate were recorded. The primary outcome was the incidence of a 10% reduction of intraoperative SctO2 from baseline or more during Caesarean birth.
RESULTS
The norepinephrine group had a lower incidence of more than 10% reduction of intraoperative SctO2 from baseline than that of the phenylephrine group (13.3% vs 40.0%, P = .02). The change in SctO2 after 5 minutes of norepinephrine infusion was higher than that after phenylephrine infusion (-3.4 ± 4.7 vs -6.2 ± 5.6, P = .04). The change in SctO2 after 10 minutes of norepinephrine infusion was higher than that after phenylephrine infusion (-2.5 ± 4.4 vs -5.4 ± 4.6, P = .006). The norepinephrine group showed greater left- and right-SctO2 values than the phenylephrine group at 5 to 10 minutes. However, the change in systolic blood pressure was comparable between the 2 groups.
CONCLUSION
Norepinephrine was more effective than phenylephrine in maintaining SctO2 when preventing spinal hypotension during Caesarean birth. However, the changes in clinical outcomes caused by differences in SctO2 between the 2 medications warrant further studies.
Topics: Pregnancy; Female; Humans; Phenylephrine; Norepinephrine; Vasoconstrictor Agents; Oxygen Saturation; Treatment Outcome; Hypotension; Cesarean Section; Anesthesia, Spinal; Double-Blind Method; Anesthesia, Obstetrical
PubMed: 38457564
DOI: 10.1097/MD.0000000000037454 -
Anesthesiology May 2024
Topics: Norepinephrine; Phenylephrine; Infusions, Intravenous; Syringes; Epinephrine
PubMed: 38457213
DOI: 10.1097/ALN.0000000000004944 -
Advances in Pharmacological and... 2024Morelloflavone and camboginol are bioactive compounds purified from (GD), which has anti-inflammatory and antihypertensive properties. The objective of this study was...
Morelloflavone and camboginol are bioactive compounds purified from (GD), which has anti-inflammatory and antihypertensive properties. The objective of this study was to examine the cardiovascular protective effect of GD flower acetone extract in 2-kidney-1-clip (2K1C) hypertensive rats. Male Wistar rats underwent 2K1C or sham operation (SO) and were housed for 4 weeks. Each group of rats, then, was further divided into 2 subgroups receiving oral administration of either 50 mg/kg BW GD extract or corn oil (vehicle) daily for 4 weeks. Noninvasive blood pressure (BP) and body weight were measured weekly throughout the study. Subsequently, the invasive measurement of arterial BP and the heart rate were determined in all anesthetized rats. The baroreceptor reflex sensitivity (BRS) was investigated by injection of either phenylephrine or sodium nitroprusside for bradycardia or tachycardia response, respectively. Histological examination of the heart and thoracic aorta was also performed in order to investigate the general morphology and the tumor necrosis factor alpha (TNF-) expression. We found that the GD flower extract significantly diminished the BP and restored the impaired BRS. Moreover, it also decreased the TNF- expression in the cardiac muscle and thoracic aorta of 2K1C when compared to the SO group. Taken together, our data showed that GD flower extract exhibits the cardiovascular protective effect in the 2K1C hypertensive rats.
PubMed: 38455637
DOI: 10.1155/2024/9916598 -
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