Showing papers on "Epinephrine published in 2008"
TL;DR: The combination of vasopressin and epinephrine during advanced cardiac life support for out-of-hospital cardiac arrest does not improve outcome and is not recommended.
Abstract: BACKGROUND During the administration of advanced cardiac life support for resuscitation from cardiac arrest, a combination of vasopressin and epinephrine may be more effective than epinephrine or vasopressin alone, but evidence is insufficient to make clinical recommendations. METHODS In a multicenter study, we randomly assigned adults with out-of-hospital cardiac arrest to receive successive injections of either 1 mg of epinephrine and 40 IU of vasopressin or 1 mg of epinephrine and saline placebo, followed by administration of the same combination of study drugs if spontaneous circulation was not restored and sub sequently by additional epinephrine if needed. The primary end point was survival to hospital admission; the secondary end points were return of spontaneous circulation, survival to hospital discharge, good neurologic recovery, and 1-year survival. RESULTS A total of 1442 patients were assigned to receive a combination of epinephrine and vasopressin, and 1452 to receive epinephrine alone. The treatment groups had similar baseline characteristics except that there were more men in the group receiving combination therapy than in the group receiving epinephrine alone (P = 0.03). There were no significant differences between the combination-therapy and the epinephrine-only groups in survival to hospital admission (20.7% vs. 21.3%; relative risk of death, 1.01; 95% confidence interval [CI], 0.97 to 1.05), return of spontaneous circulation (28.6% vs. 29.5%; relative risk, 1.01; 95% CI, 0.97 to 1.06), survival to hospital discharge (1.7% vs. 2.3%; relative risk, 1.01; 95% CI, 1.00 to 1.02), 1-year survival (1.3% vs. 2.1%; relative risk, 1.01; 95% CI, 1.00 to 1.02), or good neurologic recovery at hospital discharge (37.5% vs. 51.5%; relative risk, 1.29; 95% CI, 0.81 to 2.06). CONCLUSIONS As compared with epinephrine alone, the combination of vasopressin and epinephrine during advanced cardiac life support for out-of-hospital cardiac arrest does not improve outcome. (ClinicalTrials.gov number, NCT00127907.)
289 citations
TL;DR: Epinephrine is currently underutilized and often dosed suboptimally to treat anaphylaxis, is under‐prescribed for potential future self‐administration, and most of the reasons proposed to withhold its clinical use are flawed, but the therapeutic benefits of epinephrine exceed the risk when given in appropriate i.m. doses.
Abstract: Anaphylaxis is an acute and potentially lethal multi-system allergic reaction. Most consensus guidelines for the past 30 years have held that epinephrine is the drug of choice and the first drug that should be administered in acute anaphylaxis. Some state that properly administered epinephrine has no absolute contraindication in this clinical setting. A committee of anaphylaxis experts assembled by the World Allergy Organization has examined the evidence from the medical literature concerning the appropriate use of epinephrine for anaphylaxis. The Committee strongly believes that epinephrine is currently underutilized and often dosed suboptimally to treat anaphylaxis, is under-prescribed for potential future self-administration, that most of the reasons proposed to withhold its clinical use are flawed, and that the therapeutic benefits of epinephrine exceed the risk when given in appropriate i.m. doses.
288 citations
TL;DR: Epinephrine was associated with the development of significant but transient metabolic effects that prompted the withdrawal of 18/139 patients from the study by attending clinicians, and there was no difference in 28 and 90-day mortality.
Abstract: Objective
To determine whether there was a difference between epinephrine and norepinephrine in achieving a mean arterial pressure (MAP) goal in intensive care (ICU) patients.
278 citations
TL;DR: Recent data suggest that oxidative loss of BH4 in chronic inflammatory conditions can reduce the biosynthesis of catecholamines, which may relate to disturbed adrenergic neurotransmitter pathways in patients.
Abstract: Neurospychiatric symptoms like mood changes and depression are common in patients with chronic inflammatory disorders such as infections, autoimmune diseases or cancer. The pathogenesis of these symptoms is still unclear. Pro-inflammatory stimuli interfere not only with the neural circuits and neurotransmitters of the serotonergic, but also with those of the adrenergic system. The proinflammatory cytokine interferon-γ stimulates the biosynthesis of 5,6,7,8-tetrahydrobiopterin (BH4), which is cofactor for several aromatic amino acid monooxygenases and thus is strongly involved in the biosynthesis of the neurotransmitter serotonin and the catecholamines dopamine, epinephrine (adrenaline) and norepinephrine (noradrenaline). In macrophages, interferon-γ also triggers the high output of reactive oxygen species, which can destroy the oxidation-labile BH4. Recent data suggest that oxidative loss of BH4 in chronic inflammatory conditions can reduce the biosynthesis of catecholamines, which may relate to disturbed adrenergic neurotransmitter pathways in patients.
225 citations
TL;DR: Hemodynamic and metabolic metrics during resuscitation with lipid surpassed those with epinephrine, which were no better than those seen in the saline control group, and further studies are required to optimize the clinical management of systemic local anesthetic toxicity.
Abstract: Background: Lipid emulsion infusion reverses cardiovascular compromise due to local anesthetic overdose in laboratory and clinical settings. The authors compared resuscitation with lipid, epinephrine, and saline control in a rat model of bupivacaine-induced cardiac toxicity to determine whether lipid provides a benefit over epinephrine. Methods: Bupivacaine, 20 mg/kg, was infused in rats anesthetized with isoflurane, producing asystole in all subjects. Ventilation with 100% oxygen and chest compressions were begun immediately, along with intravenous treatment with 30% lipid emulsion or saline (5-ml/kg bolus plus continuous infusion at 0.5 ml kg -1 ·min -1 ) or epinephrine (30 μg/kg). Chest compressions were continued and boluses were repeated at 2.5 and 5 min until the native rate-pressure product was greater than 20% baseline. Electrocardiogram and arterial pressure were monitored continuously and at 10 min, arterial blood gas, central venous oxygen saturation, and blood lactate were measured. Effect size (Cohen d) was determined for comparisons at 10 min. Results: Lipid infusion resulted in higher rate-pressure product (P < 0.001, d = 3.84), pH (P < 0.01, d = 3.78), arterial oxygen tension (P < 0.05, d = 2.8), and central venous oxygen saturation (P < 0.001, d = 4.9) at 10 min than did epinephrine. Epinephrine treatment caused higher lactate (P < 0.01, d = 1.48), persistent ventricular ectopy in all subjects, pulmonary edema in four of five rats, hypoxemia, and a mixed metabolic and respiratory acidosis by 10 min. Conclusions: Hemodynamic and metabolic metrics during resuscitation with lipid surpassed those with epinephrine, which were no better than those seen in the saline control group. Further studies are required to optimize the clinical management of systemic local anesthetic toxicity.
183 citations
TL;DR: It is demonstrated that lactate production during shock states is related, at least in part, to increased Na+K+-ATPase activity under &bgr;2 stimulation and not secondary to a reduced oxygen availability.
Abstract: During septic shock, muscle produces lactate by way of an exaggerated NaK-adenosine triphosphatase (ATPase)-stimulated aerobic glycolysis associated with epinephrine stimulation possibly through beta2 adrenoreceptor involvement. It therefore seems logical that a proportion of hyperlactatemia in low cardiac output states would be also related to this mechanism. Thus, in low-flow and normal-to-high-flow models of shock, we investigate (1) whether muscle produces lactate and (2) whether muscle lactate production is linked to beta2 adrenergic stimulation and Na+K+-ATPase. We locally modulated the adrenergic pathway and Na+K+-ATPase activity in male Wistar rats' skeletal muscle using microdialysis with nonselective and selective beta blockers and ouabain in different models of rodent shock (endotoxin, peritonitis, and hemorrhage). Blood flow at the probe site was evaluated by ethanol clearance. We measured the difference between muscle lactate and blood lactate concentration, with a positive gradient indicating muscle lactate or pyruvate production. Epinephrine levels were elevated in all shock groups. All models were associated with hypotension and marked hyperlactatemia. Muscle lactate concentrations were consistently higher than arterial levels, with a mean gradient of 2.5+/-0.3 in endotoxic shock, 2.1+/-0.2 mM in peritonitis group, and 0.9+/-0.2 mM in hemorrhagic shock (P<0.05 for all groups). Muscle pyruvate concentrations were also always higher than arterial levels, with a mean gradient of 260+/-40 microM in endotoxic shock, 210+/-30 microM in peritonitis group, and 90+/-10 microM in hemorrhagic shock (P<0.05 for all groups). Despite a decrease in blood flow, lactate formation was decreased by all the pharmacological agents studied irrespective of shock mechanism. This demonstrates that lactate production during shock states is related, at least in part, to increased NaK-ATPase activity under beta2 stimulation. In shock state associated with a reduced or maintained blood flow, an important proportion of muscle lactate release is regulated by a beta2 receptor stimulation and not secondary to a reduced oxygen availability.
152 citations
TL;DR: Prospective studies are necessary to identify risk factors for severe anaphylaxis and to establish rational guidelines for prescribing multiple epinephrine autoinjectors for children with food allergy.
Abstract: Background Food allergy is the most common cause of anaphylaxis outside the hospital setting. Objective We sought to determine the rate, circumstances, and risk factors for repeated doses of epinephrine in the treatment of food-induced anaphylaxis in children. Methods Anonymous questionnaires were distributed to families of children with food allergies during allergy outpatient visits to a food allergy referral center. Demographic information, allergy and reaction history, and details regarding the last 2 anaphylactic reactions requiring epinephrine were collected. Results A total of 413 questionnaires were analyzed. Seventy-eight children (median, 4.5 years of age; range, 0.5-17.5 years) reported 95 reactions for which epinephrine was administered. Two doses were administered in 12 (13%) and 3 doses in an additional 6 (6%) reactions treated with epinephrine. Peanut, tree nuts, and cow's milk were responsible for >75% of reactions requiring epinephrine. Patients receiving multiple doses of epinephrine more often had asthma ( P = .027) than children receiving a single dose. The amount of food ingested or a delay in the initial administration of epinephrine were not risk factors for receiving multiple doses. The second dose of epinephrine was administered by a health care professional in 94% of reactions. Conclusion In this referral population of children and adolescents with multiple food allergies, 19% of food-induced anaphylactic reactions were treated with more than 1 dose of epinephrine. Prospective studies are necessary to identify risk factors for severe anaphylaxis and to establish rational guidelines for prescribing multiple epinephrine autoinjectors for children with food allergy.
152 citations
TL;DR: The blunted plasma catecholamine responses after central AT1 receptor blockade indicate that endogenous Ang II in the brain is required for sympathoadrenal activation during immobilization stress.
Abstract: Angiotensin II (Ang II) type-1 (AT1) receptors are present in areas of the brain controlling autonomic nervous activity and the hypothalamic-pituitary-adrenal (HPA) axis, including CRH cells in the hypothalamic paraventricular nucleus (PVN). To determine whether brain AT1 receptors are involved in the activation of the HPA axis and sympathetic system during stress, we studied the effects of acute immobilization stress on plasma catecholamines, ACTH and corticosterone, and mRNA levels of CRH and CRH receptors (CRH-R) in the PVN in rats under central AT1 receptor blockade by the selective antagonist, Losartan. While basal levels of epinephrine, norepinephrine and dopamine in plasma were unaffected 30 min after i.c.v. injection of Losartan (10 microg), the increases after 5 and 20 min stress were blunted in Losartan treated rats (P < 0.05 for norepinephrine, and P < 0.01 for epinephrine and dopamine, vs controls). Basal or stress-stimulated plasma ACTH and corticosterone levels were unaffected by i.c.v. Losartan treatment. Using in situ hybridization studies, basal levels of CRH mRNA and CRH-R mRNA in the PVN were unchanged after i.c.v. Losartan. While Losartan had no effect on the increases in CRH-R mRNA levels 2 or 3 h after 1 h immobilization, it prevented the increases in CRH mRNA. The blunted plasma catecholamine responses after central AT1 receptor blockade indicate that endogenous Ang II in the brain is required for sympathoadrenal activation during immobilization stress. While Ang II appears not to be involved in the acute secretory response of the HPA axis, it may play a role in regulating CRH expression in the PVN.
128 citations
TL;DR: The results of this study may help improve the safety of intra-articular pain pump use by examining the effects of local anesthetics on chondrocyte viability and the use of 0.5% bupivacaine for greater than 48 hours is not recommended.
Abstract: BackgroundChondrolysis initiated by postoperative, intra-articular pain pumps has recently been described by multiple institutions.PurposeTo evaluate the in vitro chondrotoxicity of anesthetic formulations commonly used in pain pumps.Study DesignControlled laboratory study.MethodsFreshly isolated human articular chondrocytes were cultured for 24-, 48-, and 72-hour trials in a custom bioreactor that mimics the metabolism of synovial fluid. Chondrocytes were perfused in Dulbecco's Modified Eagle's Medium 10% fetal bovine serum and one of the following medications: 1 % lidocaine, 1 % lidocaine with epinephrine, 0.25% bupivacaine, 0.25% bupivacaine with epinephrine, 0.5% bupivacaine, or 0.5% bupivacaine with epinephrine. Static and perfusion cultures with growth media were used as controls. All experiments were run in duplicate. Live/dead staining was performed, and the ratio of dead: Live cells was assessed by fluorescent microscopy and histomorphometry.ResultsSignificantly more chondrocyte necrosis was foun...
119 citations
TL;DR: Epinephrine is currently underused and often dosed suboptimally to treat anaphylaxis, is underprescribed for potential future self-administration, and most of the reasons proposed to withhold its clinical use are flawed, but the therapeutic benefits of epinephrine exceed the risk when given in appropriate intramuscular doses.
112 citations
TL;DR: In this model of a bupivacaine-induced cardiac arrest, the vasopressor combination of vasopressin and epinephrine compared with lipid emulsion resulted in higher coronary perfusion pressure during CPR and survival rates.
Abstract: BACKGROUND In a porcine model, we compared the effect of the combination of vasopressin/epinephrine with that of a lipid emulsion on survival after bupivacaine-induced cardiac arrest. METHODS After administration of 5 mg/kg of a 0.5% bupivacaine solution i.v., ventilation was interrupted for 2 +/- 0.5 (mean +/- SD) min until asystole occurred. Cardiopulmonary resuscitation (CPR) was initiated after 1 min of untreated cardiac arrest. After 2 min of CPR, 10 animals received, every 5 min, either vasopressin combined with epinephrine or 4 mL/kg of a 20% lipid emulsion. Three minutes after each drug administration, up to three countershocks (4, 4, and 6 J/kg) were administered; all subsequent shocks with 6 J/kg. Blood for determination of the plasma bupivacaine concentration was drawn throughout the experiment. RESULTS In the vasopressor group, all five pigs survived, whereas none of five pigs in the lipid group had restoration of spontaneous circulation (P < 0.01). There was no significant difference between groups in the plasma concentration of total bupivacaine. CONCLUSION In this model of a bupivacaine-induced cardiac arrest, the vasopressor combination of vasopressin and epinephrine compared with lipid emulsion resulted in higher coronary perfusion pressure during CPR and survival rates.
TL;DR: Adrenal venous sampling contributed to the localization of autonomous hypercortisolism in the setting of ACTH-independent CS or subclinical CS in patients with bilateral adrenal masses.
Abstract: Management of patients with bilateral adrenal masses and corticotropin (ACTH)-independent Cushing syndrome (CS) or subclinical CS is problematic. We report our experience with adrenal venous sampling (AVS) in the evaluation of 10 patients with bilateral masses who had ACTH-independent CS or subclinical CS. Ten patients (9 women, 1 man, mean age 56.4 years) with bilateral adrenal masses and ACTH-independent CS (n = 3) or subclinical CS (n = 7) underwent AVS. Autonomous cortisol secretion was documented in all cases with suppressed serum ACTH concentrations and lack of cortisol suppression with dexamethasone administration. Adrenal venous sampling was performed on the second day of dexamethasone administration. Cortisol and epinephrine levels were measured from each adrenal vein (AV) and from a peripheral vein (PV). Mean (± SD) maximal diameter of the adrenal masses on computed tomography was 3.3 ± 1.3 cm (range: 1.2–6.0 cm). Successful catheterization was confirmed with AV:PV epinephrine gradients. A cortisol AV:PV gradient >6.5 was consistent with a cortisol-secreting adenoma in 11 adrenal glands; 5 patients had clinically important bilateral autonomous cortisol hypersecretion, 3 had bilateral cortisol-secreting adenomas, and 2 had ACTH-independent macronodular adrenal hyperplasia. Adrenal venous sampling-guided adrenalectomy was completed in all 10 patients—2 patients had total bilateral adrenalectomy and 2 others had subtotal bilateral adrenalectomy. During a mean follow-up of 36.1 months (range: 0.7–123 months), CS or clinically important cortisol secretory autonomy did not recur. Adrenal venous sampling contributed to the localization of autonomous hypercortisolism in the setting of ACTH-independent CS or subclinical CS in patients with bilateral adrenal masses.
TL;DR: As the duration of cardiac arrest increases, a paradoxical myocardialEpinephrine response develops, in which epinephrine becomes increasingly more important to attain ROSC, but is increasingly associated with post-ROSC myocardIAL depression.
TL;DR: Pathophysiological findings strongly support the view that chronic mental stress is important in the pathogenesis of essential hypertension, with demonstrable reduction in the abundance of the transporter protein, the NET gene silencing being associated with DNA binding by the methylation‐related inhibitory transcription factor MeCP2.
Abstract: Patients with panic disorder provide a clinical model of stress. On a "good day," free from a panic attack, they show persistent stress-related changes in sympathetic nerve biology, including abnormal sympathetic nerve single-fiber firing ("salvos" of multiple firing within a cardiac cycle) and release of epinephrine as a cotransmitter. The coreleased epinephrine perhaps originates from in situ synthesis by phenylethanolamine N-methyltransferase (PNMT). In searching for biological evidence that essential hypertension is caused by mental stress—a disputed proposition—we note parallels with panic disorder, which provides an explicit clinical model of stress: (1) There is clinical comorbidity; panic disorder prevalence is increased threefold in essential hypertension. (2) For both, epinephrine cotransmission is present in sympathetic nerves. (3) In panic disorder and essential hypertension, but not in health, single-fiber sympathetic nerve firing salvos occur. (4) Tissue nerve growth factor is increased in both conditions (nerve growth factor is a stress reactant). (5) There is induction of PNMT in sympathetic nerves. Essential hypertension exhibits a further manifestation of mental stress: there is activation of noradrenergic brain stem neurons projecting to the hypothalamus and amygdala. These pathophysiological findings strongly support the view that chronic mental stress is important in the pathogenesis of essential hypertension. A hypothesis now under test is whether in both disorders, under prevailing conditions of ongoing stress, PNMT induced in sympathetic nerves acts as a DNA methylase, causing the norepinephrine transporter (NET) gene silencing that is present in both conditions. PNMT can have an intranuclear distribution, binding to DNA. We have demonstrated that the reduced neuronal noradrenaline reuptake present in both disorders does have an epigenetic mechanism, with demonstrable reduction in the abundance of the transporter protein, the NET gene silencing being associated with DNA binding by the methylation-related inhibitory transcription factor MeCP2.
TL;DR: Evidence for the interplay between cytokines, angiotensin II and nNOS in the paraventricular nucleus (PVN), for regulating sympathetic outflow in a rat model of CHF is investigated.
Abstract: Objective:
To investigate evidence for the interplay between cytokines, angiotensin II and nNOS in the paraventricular nucleus (PVN), for regulating sympathetic outflow in a rat model of CHF.
Methods and results:
Heart failure was induced in Sprague–Dawley rats by coronary artery ligation. One group of rats was treated with pentoxifylline (PTX, 30 mg/kg IP), a cytokine blocker, or vehicle, for 5 weeks. Another group of rats was pre-treated with PTX before coronary ligation to study prior cytokine blocking effect on survival. Both groups were combined in the analysis. Echocardiography demonstrated an increase in LV end-diastolic pressure and Tei index after 5 weeks in CHF rats. ELISA revealed a significant increase in plasma TNF-α and IL-1β in CHF rats. Inducible NOS (iNOS) and angiotensin receptor-type 1 (AT-1R) mRNA expressions were increased, while neuronal NOS (nNOS) was decreased in the PVN of CHF rats; these changes were reversed by PTX. PTX treatment also decreased plasma norepinephrine and epinephrine levels and improved baroreflex control of renal sympathoexcitation in CHF rats. Immunohistochemistry revealed elevated 3-nitrotyrosine formation in the heart and the PVN of CHF rats, but not in PTX treated rats.
Conclusion:
PTX decreased both peripheral and central cytokine expression, alleviated nitric oxide dysregulation, and inhibited the formation of peroxynitrite in the PVN resulting in decreased sympathoexcitation in CHF rats.
TL;DR: It would appear from the results of the present study that natural wild honey may exert its cardioprotective and therapeutic effects against epinephrine-induced cardiac disorders and vasomotor dysfunction directly, via its very pronounced total AOC and its great wealth of both enzymatic and nonenzymatic antioxidants involved in cardiovascular defense mechanisms.
Abstract: Induction of hyperadrenergic activity was experimentally achieved in urethane-anesthetized rats using epinephrine (adrenaline). Acute administration of epinephrine (100 μg/kg) for 2 hours induced several cardiac disorders and vasomotor dysfunction. Pretreatment with natural wild honey (5 g/kg) for 1 hour prior to the injection with epinephrine (100 μg/kg) protected the anesthetized normal rats from the incidence of epinephrine-induced cardiac disorders and vasomotor dysfunction. Moreover, posttreatment with natural wild honey (5 g/kg) following the injection with epinephrine (100 μg/kg) for 1 hour showed several ameliorative outcomes to the electrocardiographic parameters and vasomotor dysfunction of anesthetized stressed rats. Furthermore, natural wild honey preserved the positive inotropic effect of epinephrine in both cases. Also, the total antioxidant capacity (AOC) of natural wild honey was found to be very pronounced. Levels of both reduced glutathione and ascorbic acid (vitamin C) were con...
TL;DR: It is reported that in a large subpopulation of healthy humans the baseline epinephrine output correlated inversely with proinflammatory and positively with anti-inflammatory cytokine production, and through this mechanism intrinsic hypo- or hyperactive adrenal medullas in some individuals may shape opposite cytokine profiles.
Abstract: Immunogenetic mechanisms operating within the immune system are known to influence cytokine profiles and disease susceptibility Yet the role of the individual's neurohormonal background in these processes remains undefined Hormonal imbalances are documented in immune-related diseases, but it is unclear whether this represents a secondary phenomenon or a primary "defect" related to specific neurohormonal immune phenotype(s) We report that in a large subpopulation of healthy humans the baseline epinephrine output (but not cortisol and sex steroid hormones) correlated inversely with proinflammatory and positively with anti-inflammatory cytokine production Thus, low vs high epinephrine excretors had a 2- to 5-fold higher TNF-alpha and IL-12 production but 2-fold lower IL-10 production induced by LPS ex vivo In alternative settings, we found low baseline levels and profoundly blunted stress-induced epinephrine responses but high TNF-alpha levels in Lewis vs Fischer inbred rats Additionally, isoproterenol, a beta adrenoreceptor agonist suppressed LPS-induced TNF-alpha production, with more pronounced effect in Lewis than in Fischer rats In human monocytes, epinephrine and the beta(2) adrenoreceptor agonist fenoterol potently inhibited LPS-induced TNF-alpha and IL-12, but stimulated IL-10 production The order of potency for hormones able to inhibit IL-12 production ex vivo was: epinephrine > norepinephrine > or = 1,25-(OH)(2) vitamin D(3) > hydrocortisone This indicates that baseline epinephrine conditions cytokine responsiveness and through this mechanism intrinsic hypo- or hyperactive adrenal medullas in some individuals may shape opposite cytokine profiles Since Lewis and Fischer rats have opposite susceptibility to experimental immunological diseases, this suggests that the parallel human phenotypes could be linked to differing responsiveness and susceptibility to infections and immune/inflammatory-related conditions
TL;DR: The vascularity of different anatomical areas may account for blood flow differences following injection with saline and lidocaine.
Abstract: Summary Background: Local anaesthetic agents in combination with epinephrine are frequently used in local reconstructive procedures such as skin tumour excision and local flap closure. The purpose of this study was to measure the effect of subdermal injection of lidocaine combined with epinephrine on cutaneous blood flow in the forearm and in the face. Methods: Thirty injections were performed on the forearm and 40 injections were performed on the face in five healthy volunteers. In both anatomical regions, 0.9% phosphate buffered saline (PBS) was used as a control, and experimental injections included 1% lidocaine either alone or in combination with 1:100 000 epinephrine, and an additional combination of 1% lidocaine with 1:200 000 epinephrine used in the facial experiments. Cutaneous blood flow was measured indirectly using laser Doppler imaging (moorLDI™-Mark 2). Results: A statistically significant increase in blood flow was achieved with injection of lidocaine in the forearm compared to saline, whereas a non-statistically significant increase was achieved with saline injection compared to lidocaine in the face. This occurred in the first 5 min in the forearm and 2 min in the face. The addition of 1:100 000 epinephrine to lidocaine resulted in an immediate decrease in cutaneous blood flow which was maximal at 10 min in the forearm and 8 min in the face. This was statistically significant compared to all other injections except for the combination of 1:200 000 epinephrine with lidocaine, injected in the face. Conclusions: The vascularity of different anatomical areas may account for blood flow differences following injection with saline and lidocaine. Incisions should be delayed for 10 min in the forearm and 8 min in the face following lidocaine + epinephrine injection to allow maximal benefit to take effect. There were no significant differences between 1:100 000 and 1:200 000 epinephrine combined with lidocaine in facial injections his study.
TL;DR: To assess the safety and effectiveness of an epinephrine/lidocaine mixture administered by injection versusEpinephrine administered topically and to learn its pharmacokinetics following administration to the nasal mucosa.
Abstract: Objectives: To assess the safety and effectiveness of an epinephrine/lidocaine mixture administered by injection versus epinephrine administered topically and to learn its pharmacokinetics following administration to the nasal mucosa.
Design: A double-blind randomized controlled trial.
Methods: Patients were assigned into two groups and were injected with either epinephrine 1:100,000 and lidocaine 1% or saline alone during endoscopic nasal surgery under general anesthesia. Pledgets soaked in epinephrine 1:1,000 were used throughout the procedure in both groups. Hemodynamic measurements and catecholamine blood levels were obtained.
Results: Ten patients were randomized to the epinephrine group and 12 to the saline group. We were able to measure epinephrine and norepinephrine levels following injection in all patients. Epinephrine levels were similar in both groups immediately after injection; however, 15 minutes following injection, epinephrine was significantly higher in saline-injected patients. Mean arterial pressure and heart rate were affected by epinephrine and norepinephrine levels immediately after injection but were never elevated over the normal range. Heart rate was higher (P < .05) in the saline injected group than in the epinephrine group throughout the measurement period. The surgeons believed that the surgical field was bloodier in saline-injected patients (P < .05) however objective estimation of blood loss showed no difference.
Conclusions: Injection of epinephrine/lidocaine mixture does not produce higher blood levels of epinephrine when compared to saline injection and did not induce any harmful side effects. We postulate that the combination with lidocaine 1% may reduce the patients' stress and thus prevent higher catecholamine levels.
TL;DR: It is demonstrated that 6 weeks’ administration of the SSRI fluoxetine can amplify a wide spectrum of ANS and metabolic counterregulatory responses during hypoglycemia in healthy individuals, and this data suggest that serotonergic transmission may be an important mechanism in modulating sympathetic nervous system drive during hyp glycemic events inhealthy individuals.
Abstract: OBJECTIVE—Hypoglycemia commonly occurs in intensively-treated diabetic patients. Repeated hypoglycemia blunts counterregulatory responses, thereby increasing the risk for further hypoglycemic events. Currently, physiologic approaches to augment counterregulatory responses to hypoglycemia have not been established. Therefore, the specific aim of this study was to test the hypothesis that 6 weeks’ administration of the selective serotonin reuptake inhibitor (SSRI) fluoxetine would amplify autonomic nervous system (ANS) and neuroendocrine counterregulatory mechanisms during hypoglycemia.
RESEARCH DESIGN AND METHODS—A total of 20 healthy (10 male and 10 female) subjects participated in an initial single-step hyperinsulinemic (9 pmol · kg−1 · min−1)-hypoglycemic (means ± SE 2.9 ± 0.1 mmol/l) clamp study and were then randomized to receive 6 weeks’ administration of fluoxetine (n = 14) or identical placebo (n = 6) in a double-blind fashion. After 6 weeks, subjects returned for a second hypoglycemic clamp. Glucose kinetics were determined by three-tritiated glucose, and muscle sympathetic nerve activity (MSNA) was measured by microneurography.
RESULTS—Despite identical hypoglycemia (2.9 ± 0.1 mmol/l) and insulinemia during all clamp studies, key ANS (epinephrine, norepinephrine, and MSNA but not symptoms), neuroendocrine (cortisol), and metabolic (endogenous glucose production, glycogenolysis, and lipolysis) responses were increased (P < 0.01) following fluoxetine.
CONCLUSIONS—This study demonstrated that 6 weeks’ administration of the SSRI fluoxetine can amplify a wide spectrum of ANS and metabolic counterregulatory responses during hypoglycemia in healthy individuals. These data further suggest that serotonergic transmission may be an important mechanism in modulating sympathetic nervous system drive during hypoglycemia in healthy individuals.
TL;DR: In patients with cardiovascular disease, dual antiplatelet therapy unmasks a distinct type of platelet reactivity in response to epinephrine and ADP but not other agonists.
TL;DR: The phentolamine-induced delay of the lidocaine Tmax likely represents phentolinamine's ability to accelerate the systemic absorption of lidocane from oral tissues into the systemic circulation.
Abstract: Phentolamine mesylate accelerates recovery from oral soft tissue anesthesia in patients who have received local anesthetic injections containing a vasoconstrictor. The proposed mechanism is that phentolamine, an alpha-adrenergic antagonist, blocks the vasoconstriction associated with the epinephrine used in dental anesthetic formulations, thus enhancing the systemic absorption of the local anesthetic from the injection site. Assessments of the pharmacokinetics of lidocaine and phentolamine, and the impact of phentolamine on the pharmacokinetics of lidocaine with epinephrine were performed to characterize this potentially valuable strategy. The blood levels of phentolamine were determined following its administration intraorally and intravenously. Additionally, the effects of phentolamine mesylate on the pharmacokinetics of intraoral injections of lidocaine with epinephrine were evaluated. Sixteen subjects were enrolled in this phase 1 trial, each receiving 4 drug treatments: 1 cartridge lidocaine/epinephrine followed after 30 minutes by 1 cartridge phentolamine (1L1P), 1 cartridge phentolamine administered intravenously (1Piv), 4 cartridges lidocaine/epinephrine followed after 30 minutes by 2 cartridges phentolamine (4L2P), and 4 cartridges lidocaine/epinephrine followed by no phentolamine (4L). Pharmacokinetic parameters estimated for phentolamine, lidocaine, and epinephrine included peak plasma concentration (Cmax), time to peak plasma concentration (Tmax), area under the plasma concentration-time curve from 0 to the last time point (AUClast) or from time 0 to infinity (AUCinf), elimination half-life (t1/2), clearance (CL), and volume of distribution (Vd). The phentolamine Tmax occurred earlier following the intravenous administration of 1Piv (7 minutes than following its submucosal administration in treatment 1L1P (15 minutes) or 4L2P (11 minutes). The phentolamine t1/2, CL, and Vd values were similar for 1L1P, 1Piv, and 4L2P. The Tmax for lidocaine occurred later and the Cmax for lidocaine was slightly higher when comparing the 4L2P treatment and the 4L treatment. The phentolamine-induced delay of the lidocaine Tmax likely represents phentolamine's ability to accelerate the systemic absorption of lidocaine from oral tissues into the systemic circulation.
TL;DR: The hypothesis that the sympathetic nervous system contributes, at least in part, to the mechanism of the sensitizing effect of ethanol is supported and sympathetic tone may contribute to the initiation and progression of alcoholic liver disease.
Abstract: It is well known that ethanol preexposure sensitizes the liver to LPS hepatotoxicity. The mechanisms by which ethanol enhances LPS-induced liver injury are not completely elucidated but are known t...
TL;DR: Infants with transient tachypnea of the newborn (TTN) have relatively low levels of epinephrine, which is known to mediate fetal lung fluid absorption, which could be a valuable diagnostic and therapeutic intervention for this common condition.
Abstract: Infants with transient tachypnea of the newborn (TTN) have relatively low levels of epinephrine, which is known to mediate fetal lung fluid absorption. Providing exogenous epinephrine could be a valuable diagnostic and therapeutic intervention for this common condition. Our primary objective was to determine if inhaled racemic epinephrine is safe for the treatment of TTN. Our secondary objective was to determine its efficacy. We conducted a randomized, blinded, placebo-controlled pilot trial. Inhaled racemic epinephrine or placebo was administered to 20 newborns with TTN. Physiologic variables of cardiopulmonary function were measured during and after treatment. No infant in either the treatment or control arm experienced an adverse event, including tachycardia or hypertension. We did not detect a difference between the two groups regarding rate of resolution of tachypnea. We did not observe any adverse effects of inhaled racemic epinephrine when administered for the treatment of TTN. Larger studies are necessary to determine efficacy.
TL;DR: The results of this study indicate for the first time in dental anaesthesia that the lidocaine+clonidine combination could be a useful and safe alternative to lidocane+epinephrine for intraoral infiltration anaesthesia.
TL;DR: Combined antiplatelet therapy reduces recurrent atherothrombotic events in stable coronary disease patients; however, high residual platelet reactivity measured ex vivo still raises concerns as a condition related to treatment failure.
Abstract: Combined antiplatelet therapy reduces recurrent atherothrombotic events in stable coronary disease patients; however, high residual platelet reactivity measured ex vivo still raises concerns as a condition related to treatment failure. Alpha-2 adrenoceptor enhances platelet reactivity and might contribute to this phenomenon. For the present study, 121 stable angina patients on standard dual antiplatelet therapy (75 mg clopidogrel and 100 mg acetylsalicylic acid) were recruited. Born aggregometry was performed with adenosine diphosphate (ADP),collagen and epinephrine. To verify platelet adrenergic activity, potentiation by low-dose epinephrine and inhibition by selective alpha-2 receptor blocker atipamezole were determined. To assess the P2Y12-specific residual activity, cangrelor was used. Plasma norepinephrine, soluble CD40-ligand, high-sensitivity-C-reactive protein (hsCRP) – and in 24 subjects platelet P-selectin positivity were measured. Epinephrine – at very low concentration (10–9g/ml) – significantly potentiates (1.25 μM ADP: 26.5% vs. 43%; 5 μM ADP: 53% vs. 64.5%; collagen: 17% vs 42%, p
TL;DR: It is concluded that a 1% diphenhydramine solution should be used cautiously for the inferior alveolar nerve block and the combination lidocaine/diphenhydRAMine solution was irritating postinjection and was not as effective as a lidocane solution for pulpal anesthesia.
TL;DR: Nebulized epinephrine results in a short-lived improvement in some but not all patients with croup, and oesophageal pressures measured via a feeding tube are satisfactory for quantification of the acute response and may be a useful continuous monitoring device.
Abstract: Objectives
To demonstrate that tests of pulmonary function applicable to sick infants and small children with acute severe viral croup would provide clear, objective evidence of responsiveness to therapy with nebulized epinephrine.
TL;DR: It is demonstrated that although Epi is capable of increasing tissue cytokines in naive rats, inhibition of the beta-adrenergic effects of catecholamines exacerbates the sepsis-induced increase of selected inflammatory cytokines.
Abstract: Background:Sepsis stimulates the sympathetic nervous system. The resultant elevation in plasma catecholamines, both norepinephrine and epinephrine (Epi), might be expected to alter the expression of inflammatory cytokines, which may directly or indirectly influence muscle protein balance. The purpos
Journal Article•
TL;DR: A 79-year-old man with a history of diastolic dysfunction who was admitted for elective coronary artery bypass graft surgery and symptoms of anaphylaxis developed with urticaria and decreased mean arterial pressure was treated with methylene blue.
Abstract: Methylene blue has multiple indications for use, but recently it has been shown to be useful in treating refractory hypotension. Anaphylaxis results in widespread vasodilation and hypotension. Epinephrine has been described as the drug of choice in the treatment of hypotension for anaphylaxis, but the increased heart rate may be poorly tolerated by some patients. This case report describes a 79-year-old man with a history of diastolic dysfunction who was admitted for elective coronary artery bypass graft surgery. After induction of general anesthesia, symptoms of anaphylaxis developed with urticaria and decreased mean arterial pressure. The hypotension was refractory to vasoactive agents and volume repletion. Methylene blue was primed in the cardiopulmonary bypass pump and was effective in restoring hemodynamic stability. Furthermore, the patient required a decreased amount of vasoactive agents in the postoperative course. The suspected mechanism of action of methylene blue is inhibition of the enzyme nitric oxide synthase, which ultimately prevents the smooth muscle dilation that accompanies anaphylaxis. Methylene blue may be a valuable adjunct in the treatment of anaphylaxis and other causes of refractory hypotension.