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The Effect of Prophylactic Phenylephrine and Ephedrine Infusions on Umbilical Artery Blood pH in Women With Preeclampsia Undergoing Cesarean Delivery With Spinal Anesthesia: A Randomized, Double-Blind Trial.
Higgins, N, Fitzgerald, PC, van Dyk, D, Dyer, RA, Rodriguez, N, McCarthy, RJ, Wong, CA
Anesthesia and analgesia. 2018;(6):1999-2006
Abstract
BACKGROUND Spinal anesthesia for cesarean delivery is associated with a high incidence of hypotension. Phenylephrine results in higher umbilical artery pH than ephedrine when used to prevent or treat hypotension in healthy women. We hypothesized that phenylephrine compared to ephedrine would result in higher umbilical artery pH in women with preeclampsia undergoing cesarean delivery with spinal anesthesia. METHODS This study was a randomized double-blind clinical trial. Nonlaboring women with preeclampsia scheduled for cesarean delivery with spinal anesthesia at Prentice Women's Hospital of Northwestern Medicine were randomized to receive prophylactic infusions of phenylephrine or ephedrine titrated to maintain systolic blood pressure >80% of baseline. Spinal anesthesia consisted of hyperbaric 0.75% bupivacaine 12 mg, fentanyl 15 µg, and morphine 150 µg. The primary outcome was umbilical arterial blood pH and the secondary outcome was umbilical artery base excess. RESULTS One hundred ten women were enrolled in the study and 54 per group were included in the analysis. There were 74 and 72 infants delivered in the ephedrine and phenylephrine groups, respectively. The phenylephrine:ephedrine ratio for umbilical artery pH was 1.002 (95% confidence interval [CI], 0.997-1.007). Mean [standard deviation] umbilical artery pH was not different between the ephedrine 7.20 [0.10] and phenylephrine 7.22 [0.07] groups (mean difference -0.02, 95% CI of the difference -0.06 to 0.07; P = .38). Median (first, third quartiles) umbilical artery base excess was -3.4 mEq/L (-5.7 to -2.0 mEq/L) in the ephedrine group and -2.8 mEq/L (-4.6 to -2.2mEq/L) in the phenylephrine group (difference -0.6 mEq/L, 95% CI of the difference -1.6 to 0.3 mEq/L; P = .10). When adjusted for gestational age and infant gender, umbilical artery pH did not differ between groups. There were also no differences in the umbilical artery pH stratified by magnesium therapy or by the severity of preeclampsia. CONCLUSIONS We were unable to demonstrate a beneficial effect of phenylephrine on umbilical artery pH compared with ephedrine. Our findings suggest that phenylephrine may not have a clinically important advantage compared with ephedrine with regard to improved neonatal acid-base status when used to prevent spinal anesthesia-induced hypotension in women with preeclampsia undergoing cesarean delivery.
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A systematic review of phenytoin intoxication induced by compound phenytoin sodium, ephedrine hydrochloride and theophylline tablets in China.
Zhang, L, Li, Z, Ma, G, Han, X, Li, C, Shan, M, Chen, L
Medicine. 2018;(51):e13689
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Abstract
OBJECTIVE In this study, we aimed to review the literature on phenytoin intoxication induced by compound phenytoin sodium, ephedrine hydrochloride and theophylline tablets (CPEHTT). METHOD A literature search was performed in the following databases: WANFANG DATA, HowNet, National Library Reference and Consultation Alliance, Full-text Database of Foreign Medical Journals, PubMed and Ovid. The search terms were "Compound Phenytoin Sodium, ephedrine Hydrochloride and Theophylline Tablets," and "poisoning," or "toxicity," in Chinese and in English. RESULT Ten articles including 104 patients with CPEHTT intoxication were identified. The ages of the patients ranged from 52 to 82 years. Sixty-seven patients were male and thirty-seven patients were female (the male/female ratio, approximately 2:1). The most common clinical manifestations were dizziness (85%) and ataxia (85%), followed by limb weakness (65%), diplopia (25%), binocular horizontal nystagmus (24%), limb numbness (13%), nausea and vomiting (12%), somnolence (10%), tremor and high muscle tension (7%), lag in response (5%), dysarthria (6%), choking cough (2%), auditory hallucination and visual fantasy (1%), and involuntary movement (1%). All patients had chronic lung disease, and the most common disease was chronic bronchitis. The dosage ranged 4 to 15 tablets per day with medication duration of more than 1 year for most patients. CONCLUSION The CPEHTT intoxication caused by phenytoin toxicity represents a drug safety problem in China. The common clinical manifestations, serum phenytoin concentrations, and associated factors of CPEHTT intoxication are important for diagnosis and prevention. These findings may help guide clinicians to correctly attend to the use of CPEHTT and avoid its toxicity.
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A Review of Natural Stimulant and Non-stimulant Thermogenic Agents.
Stohs, SJ, Badmaev, V
Phytotherapy research : PTR. 2016;(5):732-40
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Abstract
Obesity and overweight are major health issues. Exercise and calorie intake control are recognized as the primary mechanisms for addressing excess body weight. Naturally occurring thermogenic plant constituents offer adjunct means for assisting in weight management. The controlling mechanisms for thermogenesis offer many intervention points. Thermogenic agents can act through stimulation of the central nervous system with associated adverse cardiovascular effects and through metabolic mechanisms that are non-stimulatory or a combination thereof. Examples of stimulatory thermogenic agents that will be discussed include ephedrine and caffeine. Examples of non-stimulatory thermogenic agents include p-synephrine (bitter orange extract), capsaicin, forskolin (Coleus root extract), and chlorogenic acid (green coffee bean extract). Green tea is an example of a thermogenic with the potential to produce mild but clinically insignificant undesirable stimulatory effects. The use of the aforementioned thermogenic agents in combination with other extracts such as those derived from Salacia reticulata, Sesamum indicum, Lagerstroemia speciosa, Cissus quadrangularis, and Moringa olifera, as well as the use of the carotenoids as lutein and fucoxanthin, and flavonoids as naringin and hesperidin can further facilitate energy metabolism and weight management as well as sports performance without adverse side effects. © 2016 The Authors Phytotherapy Research published by John Wiley & Sons Ltd.
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The effect of leptin, caffeine/ephedrine, and their combination upon visceral fat mass and weight loss.
Liu, AG, Smith, SR, Fujioka, K, Greenway, FL
Obesity (Silver Spring, Md.). 2013;(10):1991-6
Abstract
OBJECTIVE To evaluate the effects of combination caffeine/ephedrine and leptin A-200 on visceral fat mass and weight loss over 24 weeks. DESIGN AND METHODS In this randomized, double-blind, parallel-arm trial, 90 obese subjects received one of the three treatments for 24 weeks: 200 mg caffeine/20 mg ephedrine t.i.d. (CE), leptin A-200 (recombinant methionyl human Fc-leptin, 20 mg q.d.) (L), or combination leptin A-200 and caffeine/ephedrine (LCE). Outcomes included change in weight, visceral fat mass by computed tomography, lean mass and fat mass by dual energy X-ray absorptiometry. RESULTS Groups treated with CE and LCE lost significant amounts of weight (-5.9 ± 1.2% and -6.5 ± 1.1%, P < 0.05) and whole body fat mass (-9.6 ± 2.4% and -12.4 ± 2.3%, P < 0.05) compared to leptin only group. Only treatment with LCE significantly reduced visceral fat mass (-11.0 ± 3.3%, P < 0.05). There were no differences in lean mass between treatment groups. CONCLUSIONS Our study provides evidence that CE is a modestly effective weight loss agent and produces significant reductions in fat mass. Leptin A-200 was not effective in producing weight loss and did not have any significant additive or synergistic actions when combined with CE.
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Prevention of postoperative hypotension following spinal anesthesia for TURP: a double-blind randomized controlled trial comparing ephedrine with placebo.
Verdeyen, J, Ory, JP, Wyckmans, W, Vandermeersch, E, Jamaer, L, Van Assche, A
Acta anaesthesiologica Belgica. 2008;(2):73-8
Abstract
Spinal hypotension (SH) is a common side effect of spinal anesthesia and may also occur after the surgical procedure. In this double-blinded, placebo-controlled, randomised clinical trial fifty patients undergoing transurethral prostatectomy under spinal anesthesia received 10 mg of ephedrine IV before being transferred from the operating table into their bed after the procedure, whereas fifty controls received saline IV. The number of per- and postoperative hypotensive episodes and vasopressor use, time delay between the administration of the study medication and the first hypotensive episode, level of spinal blockade at the start of surgery, pre- and postoperative hemoglobine and sodium concentration, cardiovascular co-morbidity and chronic medication were registered. There was no statistically significant difference in the incidence of postoperative hypotension between the two groups, but Poisson regression of the expected number of postoperative hypotensive episodes per patient showed a protective effect of ephedrine (p < 0.05). The occurence of peroperative hypotension was a risk factor for developing postoperative hypotension (p < 0.05). There was no statistically significant relation between age, level of spinal blockade, cardiovascular co-morbidity or biochemical parameters and the risk of developing per- or postoperative hypotension, except for a correlation between preoperative alpha-receptor blocking drugs and peroperative hypotension (p < 0.05). Postoperative hypotension (recorded incidence 31%) was almost as common as peroperative hypotension (recorded incidence 37%) and occurred as late as 190 minutes after the end of surgery. Ephedrine IV at the end of surgery reduced the number of postoperative hypotensive episodes per patient but did not reduce the overall incidence of postoperative SH.
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Use of a prescribed ephedrine/caffeine combination and the risk of serious cardiovascular events: a registry-based case-crossover study.
Hallas, J, Bjerrum, L, Støvring, H, Andersen, M
American journal of epidemiology. 2008;(8):966-73
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Abstract
Ephedrine and herbal ephedra preparations have been shown to induce a small-to-moderate weight loss. Owing to reports on serious cardiovascular events, they were banned from the US market in 2004. There have been no large controlled studies on the possible association between prescribed ephedrine/caffeine and cardiovascular events in general. The authors linked data from four different sources within Statistics Denmark, using data on 257,364 users of prescribed ephedrine/caffeine for the period 1995-2002. The data were analyzed using a case-crossover technique with a composite endpoint: death outside of a hospital, myocardial infarction, or stroke. To account for effects of chronic exposure and effects in naïve users, the authors performed a secondary case-control study nested within the cohort of ephedrine/caffeine ever users. Among 2,316 case subjects, 282 (12.2%) were current users of ephedrine/caffeine. The case-crossover analysis yielded an odds ratio of 0.84 (95% confidence interval: 0.71, 1.00); after adjustment for trends in ephedrine/caffeine use, it was 0.95 (95% confidence interval: 0.79, 1.16). Subgroup analyses revealed no strata with significantly elevated risk. In the case-control substudy, there was no increased risk among naïve users or users with large cumulative doses. Prescribed ephedrine/caffeine was not associated with a substantially increased risk of adverse cardiovascular outcomes in this study.
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Water potentiates the pressor effect of ephedra alkaloids.
Jordan, J, Shannon, JR, Diedrich, A, Black, B, Robertson, D, Biaggioni, I
Circulation. 2004;(15):1823-5
Abstract
BACKGROUND The use of ephedra alkaloids in over-the-counter preparations has been associated with potentially serious cerebrovascular events. Because of its potential association with hemorrhagic strokes, phenylpropanolamine has been largely substituted for by pseudoephedrine, but it is not clear whether this is indeed a safer alternative. It would be important to understand the cardiovascular effects of ephedra alkaloids, but these are normally masked by baroreflex buffering mechanisms. We therefore investigated the effects of ephedra alkaloids in patients with autonomic impairment and explored their potential interaction with water ingestion. METHODS AND RESULTS The cardiovascular effects of phenylpropanolamine or pseudoephedrine, alone and in combination with water, were determined in 13 subjects with impairment of baroreflex function due to autonomic failure. Phenylpropanolamine, 12.5 to 25 mg PO, increased systolic blood pressure (SBP) by 21+/-14 mm Hg after 90 minutes. However, when ingested with 16 oz of room temperature tap water, phenylpropanolamine increased SBP by 82+/-2 mm Hg. Pseudoephedrine, 30 mg PO, increased SBP on average 52+/-9 mm Hg when taken with 16 oz of water and by as much as 88 mm Hg. CONCLUSIONS Ephedra alkaloids increase blood pressure significantly in individuals with impaired baroreflex function. Concomitant ingestion of ephedra alkaloids and water produced a greater increase in blood pressure. If used cautiously, this interaction can be beneficial in the treatment of orthostatic hypotension. On the other hand, it could contribute to the cardiovascular complications associated with the use of ephedra alkaloids, given that baroreflex function varies widely in normal individuals and is impaired in several medical conditions.
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Bad news for dieters: a focus on ephedrine.
Riffel, K
The Kansas nurse. 2003;(4):6-9
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Cardiac retention of [11C]HED in genotyped long QT patients: a potential amplifier role for severity of the disease.
Mazzadi, AN, André-Fouët, X, Duisit, J, Gebuhrer, V, Costes, N, Chevalier, P, Rodriguez, C, Schott, JJ, Le Marec, H, Guicheney, P, et al
American journal of physiology. Heart and circulatory physiology. 2003;(3):H1286-93
Abstract
Although mutations in cardiac sodium and potassium channel genes are associated with congenital long QT syndrome (LQTS), a "modifier" role of the sympathetic nervous system was proposed to explain the distinct severity of the disease. We evaluated cardiac sympathetic innervation using [11C]hydroxyephedrine ([11C]HED) and positron emission tomography (PET) in genotyped LQTS patients. H215O and [11C]HED PET studies were performed in 11 patients (5 symptomatic) and 8 controls. Perfusion and [11C]HED images were depicted as 36-sector polar maps. Sectorial values of perfusion (H2O%), absolute (HEDRet) and relative retention (HED%Ret) of [11C]HED, and the ratio of HED%Ret to H2O% (HED%Ret/H2O%) were calculated. Normal databases were obtained from controls. Sectorial values below 2SD database values were defined as "outside sectors." Controls and patients showed similar sectorial perfusion. Sectorial HEDRet did not differ between groups, but means of HED%Ret were lower in three sectors for patients (P < 0.05). Three sectors from 3 controls had HED%Ret below 2SD, whereas 36 sectors in 9 patients were outside sectors (P < 0.01). In patients, average HED%Ret/H2O% was lower in 9 sectors (P < 0.05 vs. controls); 2 outside sectors were found in controls, but 43 outside sectors were found in patients (P < 0.01), 77% of them in the 5 symptomatic patients. Heterogeneous [11C]HED retention was localized in the septal, anterior, and lateral walls. Most LQTS patients showed a localized and decreased pattern of [11C]HED retention. The larger number of heterogeneous sectors in symptomatic patients suggests that sympathetic function could play an amplifier role for severity of the disease.
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The effects of ginseng, ephedrine, and caffeine on cognitive performance, mood and energy.
Lieberman, HR
Nutrition reviews. 2001;(4):91-102
Abstract
A variety of claims regarding the purported energy-enhancing properties of nutritional supplements and food constituents have recently been made. It appears that the supplements most frequently associated with such assertions are ginseng, ephedrine, and caffeine. Claims of increased energy are difficult to evaluate objectively because their meaning is not usually defined or specified. Often it is not clear whether the claims refer to physical or mental energy or both. Furthermore, an agreed upon scientific definition of either physical or mental energy enhancement does not exist. In spite of obvious differences in what the term physical energy, as opposed to mental energy implies, there is no clear scientific consensus on whether there is a difference between the two types of energy. Because the substances in question have been anecdotally associated with improvements in both physical and mental performance, their effects on both functions will be discussed, but with an emphasis placed on cognitive function and mood. Of the three substances discussed, caffeine's effects on cognitive and physical function, mood, and energy are best understood. It is clear that this food/drug enhances these functions when administered in moderate doses. Ephedrine may also enhance certain physical and mental functions related to "energy," but the evidence that ginseng has such properties is exceedingly weak.