The Anti-Inflammatory Effects and Clinical Potential of Dexmedetomidine in Pulmonary Arterial Hypertension.

A pathogenic aspect of pulmonary arterial hypertension (PAH) is the aberrant pulmonary arterial smooth muscle cell (PASMC) proliferation. PASMC proliferation is significantly affected by inflammation. A selective α-2 adrenergic receptor agonist called dexmedetomidine (DEX) modulates specific inflammatory reactions. We investigated the hypothesis that anti-inflammatory characteristics of DEX could lessen PAH that monocrotaline (MCT) causes in rats. In vivo, male Sprague-Dawley rats aged 6 weeks were subcutaneously injected with MCT at a dose of 60 mg/kg. Continuous infusions of DEX (2 µg/kg per hour) were started via osmotic pumps in one group (MCT plus DEX group) at day 14 following MCT injection but not in another group (MCT group). Right ventricular systolic pressure (RVSP), right ventricular end-diastolic pressure (RVEDP), and survival rate significantly improved in the MCT plus DEX group compared with the MCT group [RVSP, 34 mmHg ± 4 mmHg versus 70 mmHg ± 10 mmHg; RVEDP, 2.6 mmHg ± 0.1 mmHg versus 4.3 mmHg ± 0.6 mmHg; survival rate, 42% versus 0% at day 29 (P < 0.01)]. In the histologic study, the MCT plus DEX group showed fewer phosphorylated p65-positive PASMCs and less medial hypertrophy of the pulmonary arterioles. In vitro, DEX dose-dependently inhibited human PASMC proliferation. Furthermore, DEX decreased the expression of interleukin-6 mRNA in human PASMCs treated with fibroblast growth factor 2 (FGF2). These consequences suggest that DEX improves PAH by inhibiting PASMC proliferation through its anti-inflammatory properties. Additionally, DEX may exert anti-inflammatory effects via blocking FGF2-induced nuclear factor κ B activation. SIGNIFICANCE STATEMENT: Dexmedetomidine, a selective α-2 adrenergic receptor agonist utilized as a sedative in the clinical setting, improves pulmonary arterial hypertension (PAH) by inhibiting pulmonary arterial smooth muscle cell proliferation through its anti-inflammatory effect. Dexmedetomidine may be a new PAH therapeutic agent with vascular reverse remodeling effect.

Protective effects of (R)-enantiomers but not (S)-enantiomers of ß2-adrenergic receptor agonists against acute colitis: The role of ß2AR.

The outcomes of ulcerative colitis (UC) treatment remain unsatisfactory. Salbutamol is a ß2-adrenergic receptor (ß2AR) agonist that is frequently used to treat human airway diseases, and it is a chiral drug with (RS)-isomers. However, the effects of (RS)-enantiomers of this drug on acute ulcerative colitis remain unknown. The present work determined and compared the effects of different chiral ß2AR agonists in acute colitis. Acute colitis was established in mice with 3% dextran sulfate sodium and the mice were orally administered different salbutamol isomers. Body weight loss, colon length, disease activity index (DAI), and colon histopathology were assessed. Inflammatory cytokine levels were detected by ELISA. Colonic biopsies were collected from colitis patients. 16S rDNA amplicon sequencing was carried out to assess the composition and relative abundance of the gut microbiome. The expression of M1 and M2 macrophage markers in the colon were assessed by immunofluorescence staining and Western blotting. The results revealed that (R)-salbutamol prevented body weight loss and colonic shortening, decreased the DAI and histopathological scores, and reduced splenomegaly and inflammatory cytokine levels significantly better than (RS)-salbutamol and (S)-salbutamol. (R)-salbutamol downregulated levels of inflammatory protein in LPS-induced human colon tissue specimens. Furthermore, (R)-salbutamol ameliorated gut dysbiosis and macrophage polarization in mice with colitis. The ß2AR antagonist ICI-118551 reversed the effect of (R)-salbutamol in ameliorating acute colitis. Taken together, (R)-salbutamol ameliorated the mice with acute colitis, which can serve as a new candidate or lead compound for UC treatment.

Nine prohibited stimulants found in sports and weight loss supplements: deterenol, phenpromethamine (Vonedrine), oxilofrine, octodrine, beta-methylphenylethylamine (BMPEA), 1,3-dimethylamylamine (1,3-DMAA), 1,4-dimethylamylamine (1,4-DMAA), 1,3-dimethylbutylamine (1,3-DMBA) and higenamine.

BACKGROUND: Weight loss and sports supplements containing deterenol have been associated with serious adverse events including cardiac arrest. OBJECTIVE: To determine the presence and quantity of experimental stimulants in dietary supplements labeled as containing deterenol sold in the United States. METHODS: Dietary supplements available for sale in the US and labeled as containing deterenol or one of its synonyms (e.g., isopropylnorsynephrine and isopropyloctopamine) were purchased online. For each brand, one container or subsample was analyzed by NSF International (Ann Arbor, MI) and one container or subsample by the Netherland's National Institute for Public Health and the Environment (RIVM, Bilthoven, The Netherlands). When differences existed between the two containers or subsamples of the same brand, both products were reanalyzed by Sciensano (Brussels, Belgium). NSF International carried out qualitative and quantitative analyses using ultra-high-performance liquid chromatography (UHPLC) quadrupole-Orbitrap mass spectrometry. RIVM performed qualitative and quantitative analysis using UHPLC quadrupole time-of-flight mass spectrometry. Sciensano carried out qualitative analysis using UHPLC quadrupole-Orbitrap mass spectrometry. RESULTS: Seventeen brands of supplements were analyzed. Many brands included more than one prohibited stimulant in the same product: 4 brands (24%, 4/17) included 2 stimulants, 2 (12%, 2/17) combined 3 stimulants, and 2 (12%, 2/17) combined 4 stimulants. The range of quantities per recommended serving size of the 9 stimulants detected were 2.7 mg to 17 mg of deterenol; 1.3 mg to 20 mg of phenpromethamine (Vonedrine); 5.7 mg to 92 mg of beta-methylphenylethylamine (BMPEA); 18 mg to 73 mg of octodrine; 18 mg to 55 mg of oxilofrine; 48 mg of higenamine; 17 mg of 1,3-dimethylamylamine (1,3-DMAA); 1.8 mg to 6.6 mg of 1,3-dimethylbutylamine (1,3-DMBA); and 5.3 mg of 1,4-dimethylamylamine (1,4-DMAA). CONCLUSION: Weight loss and sports supplements listing deterenol as an ingredient contained 9 prohibited stimulants and 8 different mixtures of stimulants, with as many as 4 experimental stimulants per product. These cocktails of stimulants have never been tested in humans and their safety is unknown.

Comparison of the Analgesic Duration of 0.5% Bupivacaine With 1:200,000 Epinephrine Versus 0.5% Ropivacaine Versus 1% Ropivacaine for Low-Volume Ultrasound-Guided Interscalene Brachial Plexus Block: A Randomized Controlled Trial.

BACKGROUND: Bupivacaine and ropivacaine are the preferred long-acting local anesthetics for peripheral nerve blocks as they provide prolonged analgesia in the postoperative period. No studies have directly compared the analgesic duration of these commonly used local anesthetics in the setting of low-volume ultrasound-guided interscalene block (US-ISB). This study was designed to determine which local anesthetic and concentration provides superior analgesia (duration and quality) for low-volume US-ISB. METHODS: Sixty eligible patients scheduled for arthroscopic shoulder surgery were randomized (1:1:1) to receive US-ISB (5 mL) with 0.5% bupivacaine with 1:200,000 epinephrine, 0.5% ropivacaine, or 1% ropivacaine. All individuals were blinded including study participants, anesthesiologists, surgeons, research personnel, and statistician. All participants received a standardized general anesthetic and multimodal analgesia. The primary outcome was duration of analgesia defined as the time from the end of injection to the time that the patients reported a significant increase in pain (>3 numeric rating scale [NRS]) at the surgical site. RESULTS: The mean duration of analgesia for 0.5% bupivacaine with 1:200,000 epinephrine, 0.5% ropivacaine, or 1% ropivacaine was 14.1 ± 7.4, 13.8 ± 4.5, and 15.8 ± 6.3 hours, respectively (analysis of variance [ANOVA], P = .51). There were no observed differences in analgesic duration or other secondary outcomes between the 3 groups with the exception of a difference in cumulative opioid consumption up to 20h00 on the day of surgery in favor of ropivacaine 0.5% over bupivacaine of minimal clinical significance. CONCLUSIONS: In the context of single-injection low-volume US-ISB, we have demonstrated a similar efficacy between equal concentrations of ropivacaine and bupivacaine. In addition, increasing the concentration of ropivacaine from 0.5% to 1% did not prolong the duration of US-ISB.

Epinephrine soaked tampons induced transient acute dilated cardiomyopathy during FESS procedure.

BACKGROUND: Epinephrine, in all modes of use, may pose a wide range of cardiotoxic events, ranging from sinus tachycardia to heart failure, life threatening arrhythmias, and even death. Because of daily and extensive use of epinephrine, these unusual and rare events tend to be forgotten by physicians. We present a case of dilated cardiomyopathy that developed following routine use of epinephrine-impregnated tampons during function endoscopic sinus (FESS) surgery. CASE PRESENTATION: A healthy, 24-year-old man with no family history of heart disease has undergone elective surgery under general anesthesia to repair the paranasal sinuses using endoscopic approach. During surgery, soon after being treated with 1: 1000 diluted epinephrine-soaked tampons, an hypertensive crisis was noticed followed by pulseless electrical activity. An extensive examination led to the diagnosis of non-ischemic dilated cardiomyopathy. After several days of heart failure medical therapy, complete resolution of all structural and functional changes was achieved. CONCLUSION: In our case, we present an unusual and rare event of acute dilated cardiomyopathy following the use of epinephrine-soaked tampons during elective FESS surgery. A prompt response was observed after several days of heart failure treatment. Awareness of the epinephrine cardiotoxic potential even in the form of soaked tampons is essential for proper diagnosis and prompt treatment.

Early Administration of Adrenaline for Out-of-Hospital Cardiac Arrest: A Systematic Review and Meta-Analysis.

Background The use of adrenaline in out-of-hospital cardiac arrest (OHCA) patients is still controversial. This study aimed to determine the effects of early pre-hospital adrenaline administration in OHCA patients. Methods and Results PubMed, EMBASE, Google Scholar, and the Cochrane Library database were searched from study inception to February 2019 to identify studies that reported OHCA patients who received adrenaline. The primary outcome was survival to discharge, and the secondary outcomes were return of spontaneous circulation, favorable neurological outcome, and survival to hospital admission. A total of 574 392 patients were included from 24 studies. The use of early pre-hospital adrenaline administration in OHCA patients was associated with a significant increase in survival to discharge (risk ratio [RR], 1.62; 95% CI, 1.45-1.83; P<0.001) and return of spontaneous circulation (RR, 1.50; 95% CI, 1.36-1.67; P<0.001), as well as a favorable neurological outcome (RR, 2.09; 95% CI, 1.73-2.52; P<0.001). Patients with shockable rhythm cardiac arrest had a significantly higher rate of survival to discharge (RR, 5.86; 95% CI, 4.25-8.07; P<0.001) and more favorable neurological outcomes (RR, 5.10; 95% CI, 2.90-8.97; P<0.001) than non-shockable rhythm cardiac arrest patients. Conclusions Early pre-hospital administration of adrenaline to OHCA patients might increase the survival to discharge, return of spontaneous circulation, and favorable neurological outcomes. Registration URL: https://www.crd.york.ac.uk/PROSPERO; Unique identifier: CRD42019130542.

FDG Uptake in Brown Adipose Tissue Activated by a ß3-Adrenergic Receptor Agonist Prescribed for Overactive Bladder.

Brown adipose tissue (BAT), which produces energy and is known to play a role as a hibernating gland, is sometimes visualized on F-FDG PET in children or in slender young adults in a cold environment. Because BAT is activated by catecholamines, FDG uptake in BAT is also observed in patients with pheochromocytoma or paraganglioma. We present the case of an elderly woman with remarkable FDG uptake in BAT. Activation of BAT by a ß3-adrenergic receptor agonist (mirabegron) prescribed for overactive bladder was suspected as the cause of the marked visualization of BAT in this patient.

Percutaneous periarticular multi-drug injection at one day after total knee arthroplasty as a component of multimodal pain management: a randomized control trial.

BACKGROUND: Although intraoperative periarticular multi-drug injection has been used for postoperative pain control after total knee arthroplasty (TKA), the injection has the inherent shortcoming of limited acting time. This randomized controlled trial was performed to assess whether adding percutaneous periarticular multi-drug injection at the day following TKA would improve the postoperative pain relief. METHODS: A total of 43 participants were randomly assigned to receive additional periarticular injection at 08:30, postoperative day 1 or no additional injection. The multi-drug solution including 40 mg of methylprednisolone, 150 mg of ropivacaine, and 0.1 mg of epinephrine was infiltrated into the muscle belly of the vastus medialis. In both groups, patients were treated with intraoperative periarticular multi-drug injection and postoperative intravenous and oral nonsteroidal anti-inflammatory drugs. We did not use any narcotic pain medications postoperatively. The primary outcome was the patients' global assessment of postoperative pain at rest measured using a visual analog scale (VAS) and quantified as the area under the curve (AUC) of serial assessments until 20:00, postoperative day 5. RESULTS: The mean AUC for the postoperative pain VAS at rest was 1616 ± 1191 in patients received the additional periarticular injection versus 2808 ± 1494 in those received no injection (mean difference, - 1192; 95% confidence interval, - 2043 to - 340; p = 0.007). No wound complication or surgical site infection was observed in either groups. CONCLUSIONS: Adding percutaneous periarticular multi-drug injection at the day following TKA may provide better postoperative pain relief. Further studies are needed to confirm the safety of the percutaneous injection. TRIAL REGISTRATION: University Hospital Medical Information Network UMIN000029003 . Registered 5 September 2017.

Prophylactic Effects of Ephedrine, Ondansetron and Ringer on Hemodynamic Changes during Cesarean Section under Spinal Anesthesia - a randomized clinical trial.

BACKGROUND: Hemodynamic change during spinal anaesthesia for cesarean section is prevalent. OBJECTIVE: Comparing the prophylactic effects of ephedrine, ondansetron and ringer on hemodynamic changes in patients undergoing cesarean section with spinal anaesthesia. MATERIAL AND METHODS: This randomized clinical trial was carried out on pregnant women undergoing elective cesarean sec-tion referred to teaching hospitals of Mashhad, Iran. Patients allocated to three groups of intravenous ondansetron (O) (4 mg, 5 min),intramuscular ephedrine (E) (25 mg, 25 min) and ringer (R) (500 ml, 20 min) prior to spinal anaesthesia. Anaesthesia inducted with 10-15 mg of bupivacaine. Vital signs were recorded every 3 minutes for 18 minutes including systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), pulse rate (PR), pulse oximetry (SpO2). RESULTS: Ninety patients with a mean age of 29.4 ± 5.4 years were studied in three groups of O (n = 30), E (n = 30), R (n = 30). Results showed a statistically significant difference in the incidence rate of hypotension 12 minutes after spinal anaesthesia in the three groups, but no statistically significant difference was found in the rest of minutes among the three groups. Dur-ing follow-up minutes, bradycardia was observed in only one patient (1.1%) of Group O and no cases of this sign were observed in other minutes and other groups. CONCLUSION: Intramuscular administration of ephedrine 25 minutes prior to the spinal anaesthesia leads to better prevention of systolic blood pressure changes compared with intravenous ondansetron and ringer, while administration of ondansetron and ringer had the same effects on reducing hemodynamic changes.

Time to Epinephrine Administration and Survival From Nonshockable Out-of-Hospital Cardiac Arrest Among Children and Adults.

BACKGROUND: Previous studies have demonstrated that earlier epinephrine administration is associated with improved survival from out-of-hospital cardiac arrest (OHCA) with shockable initial rhythms. However, the effect of epinephrine timing on patients with nonshockable initial rhythms is unclear. The objective of this study was to measure the association between time to epinephrine administration and survival in adults and children with emergency medical services (EMS)-treated OHCA with nonshockable initial rhythms. METHODS: We performed a secondary analysis of OHCAs prospectively identified by the Resuscitation Outcomes Consortium network from June 4, 2011, to June 30, 2015. We included patients of all ages with an EMS-treated OHCA and an initial nonshockable rhythm. We excluded those with return of spontaneous circulation in <10 minutes. We conducted a subgroup analysis involving patients <18 years of age. The primary exposure was time (minutes) from arrival of the first EMS agency to the first dose of epinephrine. Secondary exposure was time to epinephrine dichotomized as early (<10 minutes) or late (≥10 minutes). The primary outcome was survival to hospital discharge. We adjusted for Utstein covariates and Resuscitation Outcomes Consortium study site. RESULTS: From 55 568 EMS-treated OHCAs, 32 101 patients with initial nonshockable rhythms were included. There were 12 238 in the early group, 14 517 in the late group, and 5346 not treated with epinephrine. After adjusting for potential confounders, each minute from EMS arrival to epinephrine administration was associated with a 4% decrease in odds of survival for adults, odds ratio=0.96 (95% confidence interval, 0.95-0.98). A subgroup analysis (n=13 290) examining neurological outcomes showed a similar association (adjusted odds ratio, 0.94 per minute; 95% confidence interval, 0.89-0.98). When epinephrine was given late in comparison with early, odds of survival were 18% lower (odds ratio, 0.82; 95% confidence interval, 0.68-0.98). In a pediatric analysis (n=595), odds of survival were 9% lower (odds ratio, 0.91; 95% confidence interval, 0.81-1.01) for each minute delay in epinephrine. CONCLUSIONS: Among OHCAs with nonshockable initial rhythms, the majority of patients were administered epinephrine >10 minutes after EMS arrival. Each minute delay in epinephrine administration was associated with decreased survival and unfavorable neurological outcomes. EMS agencies should consider strategies to reduce epinephrine administration times in patients with initial nonshockable rhythms.

Sudden Tachycardia Due to Submucosal Migration of an Epinephrine-Soaked Swab During Nasal Intubation.

A 23-year-old healthy man was scheduled for extraction of his mandibular third molars under general anesthesia with nasotracheal intubation. Sudden sinus tachycardia up to 170 beats/min occurred when applying an epinephrine solution-soaked swab into the nasal cavity for preventing epistaxis during intubation. This was presumably evoked by submucosal migration of the swab into a false passage created because of the force applied during a prior failed attempt at nasal passage of the tracheal tube, and rapid epinephrine absorption by the traumatized mucosa. The causes of the unexpected severe tachycardia in our patient are discussed.

Effects of low-dose epinephrine on perioperative hemostasis and inflammatory reaction in major surgical operations: a randomized clinical trial.

Essentials Blood loss and immune reaction are closely related to morbidity and recovery after surgery. We studied the effect of epinephrine plus tranexamic acid on blood loss and immune reaction. Epinephrine plus tranexamic acid reduced postoperative total blood loss and immune reaction. Epinephrine plus tranexamic acid did not increase the incidence of complications. SUMMARY: Background Hemostasis, thrombosis and surgical stress-induced immune reactions are important for perioperative morbidity and recovery after major surgical operations. Objectives To evaluate the effects of combined administration of low-dose epinephrine (LDEPI) and tranexamic acid (TXA) on perioperative blood loss, thromboembolic complications and inflammatory responses in patients undergoing total hip arthroplasty (THA). Patients/Methods Patients scheduled for THA (n = 195) were randomized into three interventions: intravenous LDEPI plus TXA (group IV); topical diluted epinephrine plus TXA (group TP); and TXA alone as control (group CT). The primary outcome was perioperative blood loss on postoperative day (POD) 1. Secondary outcomes included perioperative blood loss on POD 3, intraoperative blood loss, volume of drainage, transfusion values, coagulation and fibrinolysis parameters, inflammatory cytokine levels, cases of thrombosis, intravenous fluid on the operation day, and length of hospital stay. Results The mean calculated amounts of total blood loss in groups IV, TP and CT were 631.2 mL, 760.5 mL, and 825.6 mL, respectively, on POD 1; treatment effects (differences) were 194.4 mL (95% confidence interval [CI] 146.7-242.0) and 65.0 mL (95% CI 17.4-112.7). Groups IV and TP had lower levels of proinflammatory cytokines (tumor necrosis factor-α and interleukin [IL]-1ß) and higher levels of the anti-inflammatory cytokine IL-10, and showed faster development of coagulation and fibrinolysis (without change in peak levels), than group CT early postoperation. No differences were observed in transfusion, thromboembolic and other outcomes among the groups. Conclusion The combined administration of LDEPI and TXA was more effective in reducing perioperative blood loss and alleviating the inflammatory response than TXA alone, without increasing the incidence of thromboembolic and other complications.

Association Between Prompt Defibrillation and Epinephrine Treatment With Long-Term Survival After In-Hospital Cardiac Arrest.

BACKGROUND: Prior studies have reported higher in-hospital survival with prompt defibrillation and epinephrine treatment in patients with in-hospital cardiac arrest (IHCA). Whether this survival benefit persists after discharge is unknown. METHODS: We linked data from a national IHCA registry with Medicare files and identified 36 961 patients ≥65 years of age with an IHCA at 517 hospitals between 2000 and 2011. Patients with IHCA caused by pulseless ventricular tachycardia or ventricular fibrillation were stratified by prompt (≤2 minutes) versus delayed (>2 minutes) defibrillation, whereas patients with IHCA caused by asystole or pulseless electric activity were stratified by prompt (≤5 minutes) versus delayed (>5 minutes) epinephrine treatment. The association between prompt treatment and long-term survival for each rhythm type was assessed with multivariable hierarchical modified Poisson regression models. RESULTS: Of 8119 patients with an IHCA caused by ventricular tachycardia or ventricular fibrillation, the rate of 1-year survival was higher in those treated with prompt defibrillation than with delayed defibrillation (25.7% [1466 of 5714] versus 15.5% [373 of 2405]; adjusted relative risk [RR], 1.49; 95% confidence interval [CI] 1.32-1.69; P<0.0001). This survival advantage persisted at 3 years (19.1% versus 11.0%; adjusted RR, 1.45; 95% CI, 1.23-1.69; P<0.0001) and at 5 years (14.7% versus 7.9%; adjusted RR, 1.50; 95% CI, 1.22-1.83; P<0.0001). Of 28 842 patients with an IHCA caused by asystole/pulseless electric activity, the rate of 1-year survival with prompt epinephrine treatment was higher than with delayed treatment (5.4% [1341 of 24 885] versus 4.3% [168 of 3957]; adjusted RR, 1.20; 95% CI, 1.02-1.41; P=0.02), but this survival benefit was no longer present at 3 years (3.5% versus 2.9%; adjusted RR, 1.17; 95% CI, 0.95-1.45; P=0.15) and at 5 years (2.3% versus 1.9%; adjusted RR, 1.18; 95% CI, 0.88-1.58; P=0.27). CONCLUSIONS: Prompt defibrillation for IHCA caused by ventricular tachycardia or ventricular fibrillation was associated with higher rates of long-term survival throughout 5 years of follow-up, whereas prompt epinephrine treatment for asystole/pulseless electric activity was associated with greater survival at 1 year but not at 3 or 5 years. By quantifying the greater survival associated with timely defibrillation and epinephrine administration, these findings provide important insights into the durability of survival benefits for 2 process-of-care measures in current resuscitation guidelines.

Time to epinephrine and survival after paediatric out-of-hospital cardiac arrest.

Aims: Delay in administration of epinephrine is associated with decreased survival among children with in-hospital cardiac arrest with an initial non-shockable rhythm. Whether this association is applicable to paediatric out-of-hospital cardiac arrest (OHCA) population remains unknown. We aimed to determine whether time to epinephrine administration is associated with outcomes in paediatric OHCA. Methods and results: This was a nation-wide population-based study of paediatric OHCA in Japan from 2005 to 2012 based on data from the All-Japan Utstein Registry. We included paediatric OHCA patients (aged between 1 and 17 years) who received at least one dose of epinephrine. The primary outcome was 30-day survival. A total of 225 patients were included in the final cohort. Among the 225 patients, 23 (10.2%) survived 30 days after OHCA. The median time from emergency call to first epinephrine administration was 26 min [interquartile range, 20-32; range, 9-128; mean (standard deviation), 28.7 (15.5) min]. Longer time to epinephrine administration was associated with decreased chance of survival: 50.0, 41.2, 13.0, 11.6, 3.9, and 3.1%, respectively, when time to epinephrine was treated as a categorical variable categorized into ≤10, 11-15, 16-20, 21-25, 26-30, or > 30 min (P for trend <0.0001), and adjusted odds ratio 0.90 (95% confidence interval 0.82-0.96, P = 0.0011) when time to epinephrine was treated as a linear and continuous variable in a multivariable logistic regression model. Similar trends were observed for prehospital return of spontaneous circulation (P = 0.0032) and neurologically favourable survival (P = 0.0014). Conclusions: Among paediatric OHCA patients, delayed administration of epinephrine was associated with a decreased chance of favourable outcomes.

Anesthetic Considerations for Patients on Antidepressant Therapy-Part I.

Millions of patients take antidepressant medications in the United States for the treatment of depression or anxiety disorders. Some antidepressants are prescribed off-label to treat problems such as chronic pain, low energy, and menstrual symptoms. Antidepressants are a broad and expansive group of medications, but the more common drug classes include tricyclic antidepressants, selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, and monoamine oxidase inhibitors. A miscellaneous or "atypical" category covers other agents. Some herbal supplements that claim to have antidepressant activity will also be discussed. In Part I of this review, antidepressant pharmacology, adverse effects, and drug interactions with adrenergic agonists will be discussed. In part II, drug interactions with sedation and general anesthetics will be reviewed. Bleeding effects and serotonin syndrome implications in anesthetic practice will also be highlighted.

Pitfalls in the use of epinephrine for anaphylaxis: patient and provider opportunities for improvement.

BACKGROUND: Epinephrine remains the mainstay of treatment for life-threatening allergic reactions. A number of challenges are encountered with epinephrine, resulting in underutilization and misutilization of epinephrine. The purpose of this study was to identify the scope of epinephrine pitfalls and opportunities for improvement in the management of allergy emergencies. METHODS: A PubMed search from 1990 to 2015 was performed to identify all cases and reports pertaining to the use and misuse of epinephrine for anaphylaxis. Studies were assessed for obstacles or complications related to proper administration of epinephrine for treatment of allergic reactions, and were divided into problems originating with patients compared to healthcare providers. RESULTS: There were 1840 publications related to epinephrine use, of which 61 reports met inclusion criteria for pitfalls in the use of epinephrine. The most common problems reported related to lack of autoinjector availability (22), inadequate education of patients or providers (9), uncertainty about when or how to administer epinephrine (9), concern for systemic effects (13), failure to administer (8), and accidental administration (2). Responsibility for errors was divided among patients (18), providers (39), or both (4). CONCLUSION: Epinephrine is a potent medication with lifesaving indications and is the standard of care for treatment of anaphylaxis. The delivery of epinephrine in both trained and untrained populations carries certain pitfalls and complications that can have serious consequences. Identification of the scope of the problem is an important step in improving education for both providers and patients who are tasked with use of epinephrine for allergy emergencies.

Clinical features and outcome of epinephrine-induced takotsubo syndrome: Analysis of 33 published cases.

BACKGROUND: Takotsubo syndrome (TS) may be triggered by innumerable physical stress factors including epinephrine administration. The aim of this study is to report on the clinical features and outcome of epinephrine-induced TS (Epi-TS) in a large cohort of published cases. METHODS: A computer assisted search of the electronic data base Pubmed was performed from 1990 to 2014. All cases deemed to have Epi-TS were retrieved and compared to the large recent report by Templin et al. (All-TS). RESULTS: Thirty-three cases of Epi-TS were retrieved from the literature and compared to 1750 cases of All-TS. Chest pain as a presenting symptom occurred in 45% of cases. The Epi-TS patients were on average 20.6years younger than All-TS patients (p<0.0001). The women were still predominating in Epi-TS but in a significantly lower percentage compared to ALL-TS (73% in Epi-TS vs 89.8% in All-TS, p=0.0054). One third of the Epi-TS cases had basal pattern of TS compared to 2.2% of cases reported in All-TS. Epi-TS cases were characterized by high complication rates, which occurred in 57.6%. The most important risk factor for the development of TS complication was the accidental administration (P<0.001) and the dose of >1mg epinephrine (p=0.02). In spite of high complication rates, the recovery was rapid with no in-hospital mortality. CONCLUSION: Epi-TS is characterized by a dramatic rapid onset of symptoms after epinephrine administration. Almost half of the cases had apical sparing and one third basal pattern of TS. In spite of high complication rates, the prognosis was good with no in-hospital mortality.