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High performance liquid chromatography determination of dexamethasone in plasma to evaluate its systemic absorption following intra-space pterygomandibular injection of twin-mix (mixture of 2 % lignocaine with 1:200,000 epinephrine and 4 mg dexamethasone): randomized control trial.
Bhargava, D, Deshpande, A, Thomas, S, Sharma, Y, Khare, P, Sahu, SK, Dubey, S, Pandey, A, Sreekumar, K
Oral and maxillofacial surgery. 2016;(3):259-64
Abstract
PURPOSE To determine systemic absorption of dexamethasone by detection of plasma concentration using high performance liquid chromatography following its administration along with local anesthetic agent as a mixture via pterygomandibular space. METHODS A prospective randomized double-blind clinical study was undertaken to analyze the plasma concentration of dexamethasone after intra-space pterygomandibular injection along with local anesthesia. The study was performed as per split mouth model where the mandibular quadrant allocation was done on a random basis considering each of the 30 patients is included in the two study interventions (SS and CS). For the study site (SS) procedures, dexamethasone was administered as a mixture (2 % lignocaine with 1:200,000 epinephrine and 4 mg dexamethasone) intra-space. In the control site (CS) procedures, a regular standard inferior alveolar nerve block was administered, and dexamethasone was given as intramuscular injection. The plasma dexamethasone determination was done in venous blood 30- and 60-min post injection using high performance liquid chromatography (HPLC). The clinical parameters like pain; swelling; and mouth opening on the first, third, and seventh post-operative day were analyzed and compared. RESULTS No significant difference was found in the clinical parameters assessed; comparative evaluation showed less swelling in the SS interventions. The plasma concentration of dexamethasone for the CS interventions was 226 ± 47 ng/ml at 30-min and 316 ± 81.6 ng/ml at 60-min post injection, and for SS, it was 221 ± 81.6 ng/ml at 30-min and 340 ± 105 ng/ml at 60-min post injection. On inter-site (CS and SS) comparison, no statistically significant difference was ascertained in dexamethasone plasma concentration at 30-min post injection (P = 0.77) and at 60-min post injection. (P = 0.32). CONCLUSION Intra-space (pterygomandibular space) administration of dexamethasone can achieve statistically similar plasma concentration of the drug as when the same dose is administered intramuscularly with demonstration of similar clinical effects.
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Impact of adrenaline and metabolic stress on exercise-induced intracellular signaling and PGC-1α mRNA response in human skeletal muscle.
Brandt, N, Gunnarsson, TP, Hostrup, M, Tybirk, J, Nybo, L, Pilegaard, H, Bangsbo, J
Physiological reports. 2016;(14)
Abstract
This study tested the hypothesis that elevated plasma adrenaline or metabolic stress enhances exercise-induced PGC-1α mRNA and intracellular signaling in human muscle. Trained (VO2-max: 53.8 ± 1.8 mL min(-1) kg(-1)) male subjects completed four different exercise protocols (work load of the legs was matched): C - cycling at 171 ± 6 W for 60 min (control); A - cycling at 171 ± 6 W for 60 min, with addition of intermittent arm exercise (98 ± 4 W). DS - cycling at 171 ± 6 W interspersed by 30 sec sprints (513 ± 19 W) every 10 min (distributed sprints); and CS - cycling at 171 ± 6 W for 40 min followed by 20 min of six 30 sec sprints (clustered sprints). Sprints were followed by 3:24 min:sec at 111 ± 4 W. A biopsy was obtained from m. vastus lateralis at rest and immediately, and 2 and 5 h after exercise. Muscle PGC-1α mRNA content was elevated (P < 0.05) three- to sixfold 2 h after exercise relative to rest in C, A, and DS, with no differences between protocols. AMPK and p38 phosphorylation was higher (P < 0.05) immediately after exercise than at rest in all protocols, and 1.3- to 2-fold higher (P < 0.05) in CS than in the other protocols. CREB phosphorylation was higher (P < 0.05) 2 and 5 h after exercise than at rest in all protocols, and higher (P < 0.05) in DS than CS 2 h after exercise. This suggests that neither plasma adrenaline nor muscle metabolic stress determines the magnitude of PGC-1α mRNA response in human muscle. Furthermore, higher exercise-induced changes in AMPK, p38, and CREB phosphorylation are not associated with differences in the PGC-1α mRNA response.
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Racemic adrenaline and inhalation strategies in acute bronchiolitis.
Skjerven, HO, Hunderi, JO, Brügmann-Pieper, SK, Brun, AC, Engen, H, Eskedal, L, Haavaldsen, M, Kvenshagen, B, Lunde, J, Rolfsjord, LB, et al
The New England journal of medicine. 2013;(24):2286-93
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Abstract
BACKGROUND Acute bronchiolitis in infants frequently results in hospitalization, but there is no established consensus on inhalation therapy--either the type of medication or the frequency of administration--that may be of value. We aimed to assess the effectiveness of inhaled racemic adrenaline as compared with inhaled saline and the strategy for frequency of inhalation (on demand vs. fixed schedule) in infants hospitalized with acute bronchiolitis. METHODS In this eight-center, randomized, double-blind trial with a 2-by-2 factorial design, we compared inhaled racemic adrenaline with inhaled saline and on-demand inhalation with fixed-schedule inhalation (up to every 2 hours) in infants (<12 months of age) with moderate-to-severe acute bronchiolitis. An overall clinical score of 4 or higher (on a scale of 0 to 10, with higher scores indicating more severe illness) was required for study inclusion. Any use of oxygen therapy, nasogastric-tube feeding, or ventilatory support was recorded. The primary outcome was the length of the hospital stay, with analyses conducted according to the intention-to-treat principle. RESULTS The mean age of the 404 infants included in the study was 4.2 months, and 59.4% were boys. Length of stay, use of oxygen supplementation, nasogastric-tube feeding, ventilatory support, and relative improvement in the clinical score from baseline (preinhalation) were similar in the infants treated with inhaled racemic adrenaline and those treated with inhaled saline (P>0.1 for all comparisons). On-demand inhalation, as compared with fixed-schedule inhalation, was associated with a significantly shorter estimated mean length of stay--47.6 hours (95% confidence interval [CI], 30.6 to 64.6) versus 61.3 hours (95% CI, 45.4 to 77.2; P=0.01) - as well as less use of oxygen supplementation (in 38.3% of infants vs. 48.7%, P=0.04), less use of ventilatory support (in 4.0% vs. 10.8%, P=0.01), and fewer inhalation treatments (12.0 vs. 17.0, P<0.001). CONCLUSIONS In the treatment of acute bronchiolitis in infants, inhaled racemic adrenaline is not more effective than inhaled saline. However, the strategy of inhalation on demand appears to be superior to that of inhalation on a fixed schedule. (Funded by Medicines for Children; ClinicalTrials.gov number, NCT00817466; EudraCT number, 2009-012667-34.).
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Effect of adrenaline on survival in out-of-hospital cardiac arrest: A randomised double-blind placebo-controlled trial.
Jacobs, IG, Finn, JC, Jelinek, GA, Oxer, HF, Thompson, PL
Resuscitation. 2011;(9):1138-43
Abstract
BACKGROUND There is little evidence from clinical trials that the use of adrenaline (epinephrine) in treating cardiac arrest improves survival, despite adrenaline being considered standard of care for many decades. The aim of our study was to determine the effect of adrenaline on patient survival to hospital discharge in out of hospital cardiac arrest. METHODS We conducted a double blind randomised placebo-controlled trial of adrenaline in out-of-hospital cardiac arrest. Identical study vials containing either adrenaline 1:1000 or placebo (sodium chloride 0.9%) were prepared. Patients were randomly allocated to receive 1 ml aliquots of the trial drug according to current advanced life support guidelines. Outcomes assessed included survival to hospital discharge (primary outcome), pre-hospital return of spontaneous circulation (ROSC) and neurological outcome (Cerebral Performance Category Score - CPC). RESULTS A total of 4103 cardiac arrests were screened during the study period of which 601 underwent randomisation. Documentation was available for a total of 534 patients: 262 in the placebo group and 272 in the adrenaline group. Groups were well matched for baseline characteristics including age, gender and receiving bystander CPR. ROSC occurred in 22 (8.4%) of patients receiving placebo and 64 (23.5%) who received adrenaline (OR=3.4; 95% CI 2.0-5.6). Survival to hospital discharge occurred in 5 (1.9%) and 11 (4.0%) patients receiving placebo or adrenaline respectively (OR=2.2; 95% CI 0.7-6.3). All but two patients (both in the adrenaline group) had a CPC score of 1-2. CONCLUSION Patients receiving adrenaline during cardiac arrest had no statistically significant improvement in the primary outcome of survival to hospital discharge although there was a significantly improved likelihood of achieving ROSC.
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Impact of high-fat /low-carbohydrate, high-, low-glycaemic index or low-caloric meals on glucose regulation during aerobic exercise in Type 2 diabetes.
Ferland, A, Brassard, P, Lemieux, S, Bergeron, J, Bogaty, P, Bertrand, F, Simard, S, Poirier, P
Diabetic medicine : a journal of the British Diabetic Association. 2009;(6):589-95
Abstract
AIMS: A decrement in blood glucose (BG) may be observed in patients with Type 2 diabetes (T2DM) when exercise is performed after a meal, in contrast to fasting. We determined the impact of different pre-exercise meal macronutrient compositions with modulation of the glycaemic index (GI) on glucose regulation during exercise in patients with T2DM. METHODS Using a randomized, single-blind crossover design, 10 sedentary men performed five exercise sessions, once after an overnight fast, and also after each of four test meals, consisting of a high-fat/low-carbohydrate meal, a high-GI meal, a low-GI meal, and a low-calorie meal. RESULTS Pre-exercise BG and insulin levels were comparable for all four meals. Exercise decreased BG and insulin levels during all meal conditions (all P < 0.001) compared with the fasting state in which BG levels did not change. The magnitude of BG and insulin decrements was similar after consuming the low-calorie, the high-GI and the high-fat/low-carbohydrate meals, whereas the low-GI meal induced the lowest BG fall. Adrenaline response was higher after consumption of the high-, the low-GI and the low-caloric meals compared with the high-fat/low-carbohydrate meal and with the fasting state (P < 0.05). CONCLUSIONS This study underlines the beneficial effect of low-GI foods and the differential impact of pre-exercise meal macronutrient composition on BG decrease. This may protect against exercise-induced hypoglycaemia, and reiterates the safety of exercising while fasting in T2DM patients.
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Large-volume endoscopic injection of epinephrine plus normal saline for peptic ulcer bleeding.
Liou, TC, Chang, WH, Wang, HY, Lin, SC, Shih, SC
Journal of gastroenterology and hepatology. 2007;(7):996-1002
Abstract
BACKGROUND AND AIM Large-volume endoscopic injection of epinephrine has been proven to significantly reduce rates of recurrent peptic ulcer bleeding. Injection of normal saline may be equally effective for the similar hemostatic effect of local tamponade. The aim of our study was to compare the therapeutic effects of large-volume (40 mL) endoscopic injections of epinephrine, normal saline and a combination of the two in patients with active bleeding ulcers. METHOD A total of 216 patients with actively bleeding ulcers (spurting or oozing) were randomly assigned to three groups (1:10,000 epinephrine, normal saline or diluted epinephrine plus normal saline). The hemostatic effects and clinical outcomes were compared between the three groups. RESULTS The initial hemostatic rate was significantly lower in the normal saline group (P < 0.05). The volume of injected solution required for the arrest of bleeding was significantly larger in the normal saline group (P < 0.01). Mean duration for arrest of bleeding was significantly longer in the normal saline group (P < 0.01). There were no significant differences between the three groups with respect to the rates of recurrent bleeding, surgical intervention, 30-day mortality, amount of transfusion and duration of hospitalization. Significant elevation of systolic blood pressure (P < 0.05) and persistent high pulse rate after endoscopic injection were observed in the epinephrine group. CONCLUSIONS For patients with active bleeding ulcers (spurting or oozing), we recommend a large-volume (40 mL) combination injection using diluted epinephrine to cease bleeding, followed by injection of normal saline to achieve sustained hemostasis.
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The metabolic and renal effects of adrenaline and milrinone in patients with myocardial dysfunction after coronary artery bypass grafting.
Heringlake, M, Wernerus, M, Grünefeld, J, Klaus, S, Heinze, H, Bechtel, M, Bahlmann, L, Poeling, J, Schön, J
Critical care (London, England). 2007;(2):R51
Abstract
INTRODUCTION Myocardial dysfunction necessitating inotropic support is a typical complication after on-pump cardiac surgery. This prospective, randomized pilot study analyzes the metabolic and renal effects of the inotropes adrenaline and milrinone in patients needing inotropic support after coronary artery bypass grafting (CABG). METHODS During an 18-month period, 251 patients were screened for low cardiac output upon intensive care unit (ICU) admission after elective, isolated CABG surgery. Patients presenting with a cardiac index (CI) of less than 2.2 liters/minute per square meter upon ICU admission - despite adequate mean arterial (titrated with noradrenaline or sodium nitroprusside) and filling pressures - were randomly assigned to 14-hour treatment with adrenaline (n = 7) or milrinone (n = 11) to achieve a CI of greater than 3.0 liters/minute per square meter. Twenty patients not needing inotropes served as controls. Hemodynamics, plasma lactate, pyruvate, glucose, acid-base status, insulin requirements, the urinary excretion of alpha-1-microglobuline, and creatinine clearance were determined during the treatment period, and cystatin-C levels were determined up to 48 hours after surgery (follow-up period). RESULTS After two to four hours after ICU admission, the target CI was achieved in both intervention groups and maintained during the observation period. Plasma lactate, pyruvate, the lactate/pyruvate ratio, plasma glucose, and insulin doses were higher (p < 0.05) in the adrenaline-treated patients than during milrinone or control conditions. The urinary excretion of alpha-1-microglobuline was higher in the adrenaline than in the control group 6 to 14 hours after admission (p < 0.05). No between-group differences were observed in creatinine clearance, whereas plasma cystatin-C levels were significantly higher in the adrenaline than in the milrinone or the control group after 48 hours (p < 0.05). CONCLUSION This suggests that the use of adrenaline for the treatment of postoperative myocardial dysfunction - in contrast to treatment with the PDE-III inhibitor milrinone - is associated with unwarranted metabolic and renal effects.
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Urinary catecholamine levels in daily life are elevated in women at familial risk of breast cancer.
James, GD, Berge-Landry Hv, Hv, Valdimarsdottir, HB, Montgomery, GH, Bovbjerg, DH
Psychoneuroendocrinology. 2004;(7):831-8
Abstract
Recent experimental research has shown that women facing the chronic stress of being at familial risk of breast cancer have greater neuroendocrine reactivity responses to stressful laboratory tasks. Whether this enhanced stress response also occurs outside the laboratory under daily life conditions is unknown. In the present study, urinary epinephrine and norepinephrine excretion rates at work (e.g. 11:00 AM-3:00 PM), home (e.g. 6:00 PM-10:00 PM) and during sleep (e.g. 10:00 PM-6:00 AM) were compared between 73 employed women with family histories of breast cancer in first degree relatives (FH+; age=36.8+/-8.7) and 81 without such family histories (FH-; age=38.1+/-9.4). Differences in sympathetic adrenal medullary responses to an ordinary life stressor (work) were assessed in naturalistic settings. Repeated measures MANCOVA with family history group as a fixed factor, body mass index as a covariate and daily microenvironment (work, home and sleep) as a repeating factor were conducted to evaluate whether catecholamine excretion rates differed between FH+ and FH- groups. The results revealed that women with family histories of breast cancer had a higher rate of epinephrine excretion while at work (p<0.005). In addition, women in the FH+ group were also more reactive to the stress of work, showing a greater percentage of increase in both epinephrine and norepinephrine from sleep to work (p<0.05). The results also indicated that the chronic stress effects associated with a family history of breast cancer were moderated by BMI, such that their impact was more pronounced and apparent when women were not obese. These findings support the idea that the heightened neuroendocrine reactivity to experimental stressors in women at familial risk of breast cancer also occurs when women encounter stressors in ordinary life (work stress). Additional research to explore the health consequences of increased reactivity in women at familial risk of breast cancer, and perhaps in individuals at familial risk of other life-threatening disease, would appear warranted.
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Randomized controlled trial of nebulized adrenaline in acute bronchiolitis.
Hariprakash, S, Alexander, J, Carroll, W, Ramesh, P, Randell, T, Turnbull, F, Lenney, W
Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology. 2003;(2):134-9
Abstract
Use of both l-epinephrine and racemic epinephrine (adrenaline) has improved clinical symptoms and composite respiratory scores in acute bronchiolitis. The objective of this randomized double-blind placebo-controlled study was to assess whether there was sufficient improvement in clinical state to reduce hospital admissions. Seventy-five infants aged 1 month to 1 year with a clinical diagnosis of acute bronchiolitis were treated with either 2 ml of 1:1000 nebulized adrenaline or 2 ml of nebulized normal saline administered after baseline assessment and 30 min later. Clinical respiratory parameters were recorded at 15-min intervals for a period of 2 h following the baseline assessment. Admission to hospital was the primary end-point and changes in respiratory parameters were secondary end-points. Fifty percent (19/38) of infants treated with adrenaline were discharged home compared with 38 percent (14/37) of those treated with saline. This 12 percent reduction in rate of admission is not statistically significant (95% CI of difference: -10% to 35%). There was no difference between treated and placebo groups in respiratory rate, oxygen saturation, heart rate or a composite respiratory distress score at 30, 60 or 120 min post-treatment. In this study, nebulized epinephrine did not confer a significant advantage over nebulized saline in the emergency room treatment of acute bronchiolitis.
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Caffeine affects cardiovascular and neuroendocrine activation at work and home.
Lane, JD, Pieper, CF, Phillips-Bute, BG, Bryant, JE, Kuhn, CM
Psychosomatic medicine. 2002;(4):595-603
Abstract
OBJECTIVE This study investigated the effects of moderate doses of caffeine on ambulatory blood pressure and heart rate, urinary excretion of epinephrine, norepinephrine, and cortisol, and subjective measures of stress during normal activities at work and at home in the evening. METHODS Healthy, nonsmoking, habitual coffee drinkers (N = 47) participated in 3 days of ambulatory study. After a day of ad lib caffeine consumption, caffeine (500 mg) and placebo were administered double-blind in counter-balanced order on separate workdays. Ambulatory blood pressure and heart rate were monitored from the start of the workday until bedtime. Urinary excretion of catecholamines and cortisol was assessed during the workday and evening. RESULTS Caffeine administration significantly raised average ambulatory blood pressure during the workday and evening by 4/3 mm Hg and reduced average heart rate by 2 bpm. Caffeine also increased by 32% the levels of free epinephrine excreted during the workday and the evening. In addition, caffeine amplified the increases in blood pressure and heart rate associated with higher levels of self-reported stress during the activities of the day. Effects were undiminished through the evening until bedtime. CONCLUSIONS Caffeine has significant hemodynamic and humoral effects in habitual coffee drinkers that persist for many hours during the activities of everyday life. Furthermore, caffeine may exaggerate sympathetic adrenal-medullary responses to the stressful events of normal daily life. Repeated daily blood pressure elevations and increases in stress reactivity caused by caffeine consumption could contribute to an increased risk of coronary heart disease in the adult population.