Higher Epinephrine Research Articles

The impact of diastolic blood pressure values on the neurological outcome of cardiac arrest patients

AimWhich haemodynamic variable is the best predictor of neurological outcome remains unclear. We investigated the association of several haemodynamic variables with neurological outcome in CA patients. MethodsRetrospective analysis of adult comatose survivors of CA admitted to the intensive care unit (ICU) of a University Hospital. Exclusion criteria were early death due to withdrawal of care, missing haemodynamic data and use of intra-aortic balloon pump or extracorporeal membrane oxygenation. We retrieved CA characteristics; lactate concentration and cardiovascular sequential organ failure assessment (cSOFA) score on admission; systolic (SAP), diastolic (DAP), mean arterial pressure (MAP), and the use of vasopressors and inotropic agents during the first 6 h of ICU stay. Unfavourable neurological outcome (UO) was defined as a 3-month cerebral performance category score of 3–5. ResultsAmong the 170 patients (median age 63 years, 67% male, 60% out-of-hospital CA), 106 (63%) had UO. Admission lactate was higher in patients with UO than in those with favourable neurological outcome (4.0[2.4–7.3] vs. 2.5[1.4–6.0] mEq/L; p = 0.003) as was the cSOFA (3 [1–4] vs. 2[0–3]; p = 0.007). The lowest DAP during the first 6 h after ICU admission was significantly lower in patients with unfavourable neurological outcome, notably in patients with high cSOFA scores. In multivariable analysis, high adrenaline doses and the lowest value of DAP during the first 6 h after ICU admission was significantly associated with unfavourable neurological outcome. ConclusionsIn CA patients admitted to the ICU, low DAP during the first 6 h is an independent predictor of unfavourable neurological outcome at 3 months.

Does Hypoglycemia Awareness Status on Gold and Clark Questionnaires Predict Hormonal and Symptomatic Responses to Hypoglycemia (HG) in Type 1 Diabetes (T1D)?

Impaired awareness of hypoglycemia (IAH) is characterized by the diminished ability to perceive symptoms of HG. Gold and Clark questionnaires are commonly used in research to identify patients with IAH. However, the relationship between IAH status on questionnaires and the symptom and counterregulatory (CR) hormone responses to HG are not well understood. In this study, we examined data from 51 research subjects with T1D who completed both questionnaires and underwent a hyperinsulinemic hypoglycemic clamp (target glucose 50 mg/dL) on the same day. Clarke and Gold scores were highly correlated with one another (r = 0.78) and each had a similar relationship with epinephrine (EPI) response during HG (Clarke: r = -0.46, Gold: r = -0.53) and symptom response (Clarke: r = -0.60, Gold: r = -0.52). However, Clarke and Gold disagreed on classification of HG awareness status (misclassification=37%, Cohen’s κ=0.54). Clarke classifications were: 26 Aware (A), 13 Indeterminate (I), 12 Unaware (U), whereas Gold classifications were 16 A, 15 I, and 20 U. A mixture model based clustering identified 3 patterns in joint EPI and symptom responses. Cluster 1 subjects (n=10) had low symptom (<5) and EPI responses (<140) to HG and 8/10 were classified as U by one or both questionnaires. Cluster 3 subjects (n=9) had high symptom (20+) and EPI responses (450+) to HG and 8 of 9 were classified as A by one or both questionnaires. Cluster 2 subjects (n=22) had intermediate symptom and EPI responses to HG but concordance of classification by Clarke and Gold was true for only 11 of the 24. Clarke classified cluster 2 subjects as 12 A, 7 I, and 3 U whereas Gold classified the same subjects into 6 A, 7 I, and 9 U. IAH classification may be discordant between Clark and Gold questionnaires and may not always correlate with the CR responses during experimental HG. To ensure reproducibility, researchers must be rigorous and consistent in defining the awareness status of study subjects. Disclosure N. Rubin: None. A. Moheet: None. L.E. Eberly: None. A. Kumar: None. S. Mangia: None. E.R. Seaquist: Advisory Panel; Self; Eli Lilly and Company. Consultant; Self; Eli Lilly and Company, Sanofi, Zucera, InfoMed, 360 consulting. Other Relationship; Self; Novo Nordisk Inc..

Can red blood cell distribution width predict outcome after cardiac arrest?

In critically ill patients, high red blood cell distribution width (RDW) values have been associated with increased hospital mortality, but there are no data on the impact of RDW on outcomes of patients resuscitated from cardiac arrest (CA). The aim of this study was to investigate the relationship between RDW and long-term neurologic outcome in CA survivors. We performed a retrospective analysis of an institutional database including all unconscious adult patients admitted to the intensive care unit (ICU) after non-traumatic CA between January 2007 and January 2015. Patients who survived <24 hours were excluded. The RDW (normal values 10.9-13.4%) was obtained daily from the day of admission to day 3. Patients with a cerebral performance category (CPC) score of 3-5 at 3 months were considered to have an unfavourable neurological outcome. Three hundred and ninety patients were included. The ICU mortality rate was 56% (N.=220) and 64% of patients (N.=251) had an unfavorable 3-month neurological outcome. The median RDW on the day of admission was 14% (13.0-15.2%) and remained stable over the observation period. Two hundred and forty-five patients (63%) had a high RDW (>13.4%) on admission. In multivariable logistic regression analysis, older age, absence of bystander cardiopulmonary resuscitation (CPR), a non-cardiac etiology of the arrest, a non-shockable initial rhythm, high adrenaline dose during CPR and high admission RDW levels were independently associated with an unfavorable outcome at 3 months. High RDW values are associated with poor neurological outcome among CA survivors.

Effects of Trilostane on urinary Catecholamines and their metabolites in dogs with Hypercortisolism

BackgroundGlucocorticoids influence the synthesis and metabolism of catecholamines (epinephrine and norepinephrine) and metanephrines (metanephrine and normetanephrine). The aim of this study was to measure urinary catecholamines and metanephrines in dogs with hypercortisolism before and during trilostane therapy.Urine samples were collected during initial work up and during therapy with trilostane in 14 dogs with hypercortisolism and in 25 healthy dogs. Epinephrine, norepinephrine, metanephrine and normetanephrine were measured using high-pressure liquid chromatography and expressed as ratios to urinary creatinine concentration.ResultsUntreated dogs with hypercortisolism had significantly higher epinephrine, norepinephrine, and normetanephrine:creatinine ratios compared to healthy dogs. During trilostane therapy, urinary catecholamines and their metabolites did not decrease significantly. However, dogs with low post-ACTH cortisol concentrations during trilostane therapy had less increased epinephrine, norepinephrine and normetanephrine:creatinine ratios compared to healthy dogs. There was no correlation of urinary catecholamines and their metabolites with baseline or post-ACTH cortisol or endogenous ACTH concentrations during trilostane therapy.ConclusionInfluences between steroid hormones and catecholamines seem to occur, as dogs with hypercortisolism have significantly higher urinary epinephrine, norepinephrine, and normetanephrine:creatinine ratios. Once-daily trilostane therapy does not lead to a significant decrease in catecholamines and their metabolites. Trilostane-treated dogs still have increased urinary epinephrine, norepinephrine and normetanephrine:creatinine ratios during trilostane therapy.

The incidence and characteristics of 3-month mortality after intraoperative cardiac arrest in adults.

There is little information about clinical outcomes after intraoperative cardiac arrest (IOCA). We determined the incidence and characteristics of 3-month mortality after IOCA. The electronic medical records of 238,648 adult surgical patients from January 2005 to December 2014 were reviewed retrospectively. Characteristics of IOCA were documented using the Utstein reporting template. IOCA occurred in 50 patients (21/100,000 surgeries). Nineteen patients died in the operating room, and further 12 patients died within 3months post-arrest (total mortality: 62%). Three survivors at 3months post-arrest had unfavourable neurological outcome. Finally, 34 patients showed unfavourable clinical outcomes at 3months post-arrest. The incidences of non-cardiac surgery, emergency, pre-operative intubation state, non-shockable initial cardiac rhythm, hypovolaemic shock, pre-operative complications-induced cardiac arrest, non-anaesthetic cause of cardiac arrest, intra- and post-arrest transfusion, and continuous infusion of inotrope or vasopressor in intensive care unit (ICU) were significantly higher in non-survivors at 3months post-arrest. Total epinephrine dose administrated during arrest was higher, and the duration of cardiac compressions was longer in non-survivors at 3months post-arrest. In this study, the incidence of IOCA was 21/100,000 surgeries and the 3-month mortality rate after IOCA was 62%. Several factors including surgical emergency, non-shockable initial cardiac rhythm, pre-operative complications, surgical complications, long duration of cardiac compressions, high total epinephrine dose, transfusion, and continuous infusion of inotropes or vasopressors in ICU seemed to be risk factors for 3-month mortality after IOCA. These risk factors should be considered in the light of relatively small sample size of this study.

Effects of epinephrine exposure on contractile performance of compact and spongy myocardium from rainbow trout (Oncorhynchus mykiss) during hypoxia

Hypoxia results in elevated circulating epinephrine for many fish species, and this is likely important for maintaining cardiac function. The aims of this study were to assess how hypoxia impacts contractile responses of ventricular compact and spongy myocardium from rainbow trout (Oncorhynchus mykiss) and to assess how and if epinephrine may protect myocardial performance from a depressive effect of hypoxia. Work output and maximum contraction rate of isolated preparations of spongy and compact ventricular myocardium from rainbow trout were measured. Tissues were exposed to the blood PO2 that they experience in vivo during environmental normoxia and hypoxia and also to low (5nM) and high (500nM) levels of epinephrine in 100% air saturation (PO2 20.2kPa) and during hypoxia (PO2 2kPa, 10% air saturation). It was hypothesized that hypoxia would result in a decrease in work output and maximum contraction rate in both tissue types, but that epinephrine exposure would mitigate the effect. Hypoxia resulted in a decline in net work output of both tissue types, but a decline in maximum contraction rate of only compact myocardium. Epinephrine restored the maximum contraction rate of compact myocardium in hypoxia, appeared to slightly enhance work output of only compact myocardium in air saturation but surprisingly not during hypoxia, and restored net work of hypoxic spongy myocardium toward normoxic levels. These results indicate hypoxia has a similar depressive effect on both layers of ventricular myocardium, but that high epinephrine may be important for maintaining inotropy in spongy myocardium and chronotropy in compact myocardium during hypoxia.

Sympathoadrenal activation and endotheliopathy are drivers of hypocoagulability and hyperfibrinolysis in trauma: A prospective observational study of 404 severely injured patients.

One third of severely injured patients present with a laboratory-based diagnosis of coagulopathy. This study investigated clinical and biomarker profile of patients with rapid thrombelastography (rTEG) coagulopathy, hypothesizing that sympathoadrenal activation and endothelial damage were drivers of this condition. Prospective observational study of 404 trauma patients admitted to a Level 1 US Trauma Center. Patients with admission rTEG and plasma measurements of catecholamines (adrenaline, noradrenaline) and biomarkers reflecting endothelial activation/damage (syndecan-1, thrombomodulin, sE-selectin, sVE-cadherin, nucleosomes) were included. Demography, injury type/severity, physiology, treatment, and inhospital mortality were recorded. Patients had a median Injury Severity Score (ISS) of 17, 73% from blunt injury. One third (35%) of the patients had rTEG coagulopathy, which was associated with higher plasma adrenaline, syndecan-1, and nucleosomes (all <0.05), higher transfusion requirements and higher early (<24 hours, 9.3% vs. 2.5%) and late (28 days, 23.8% vs. 13.4%) mortality. By adjusted linear regression analyses, high plasma adrenaline, sVE-cadherin, and syndecan-1 (reflecting sympathoadrenal activation and endothelial cell junction and glycocalyx damage) along with male sex, high ISS, low platelet count and prehospital red blood cell transfusion were independently associated with hypocoagulable rTEG, whereas prehospital plasma and sE-selectin (reflecting endothelial activation) were independently associated with more hypercoagulable rTEG. In this cohort of severely injured trauma patients, rTEG coagulopathy was associated with sympathoadrenal activation, endotheliopathy, and excess mortality. High adrenaline and biomarkers reflecting endothelial cell junction and glycocalyx damage were independently associated with hypocoagulability and hyperfibrinolysis. These findings support that sympathoadrenal activation and endotheliopathy contribute to trauma-induced coagulopathy and warrants further studies of endothelial repair management. Prognostic, Level III.

Use of local anesthesia in ear surgery: technique, modifications, advantages, and limitations over 30 years’ experience

Background Local anesthesia (LA) is safe and well established for a variety of ear operations. It has many advantages compared with general anesthesia (GA). Objective This article is intended to be a comprehensive reference for those who use this art, in which we have more than 30 years of experience. We also aimed to find out the effect of LA on blood pressure (BP) and heart rate (HR), operative time, time of anesthesia with different adrenaline concentrations, and patient satisfaction with LA. Patients and methods This was a retrospective study of our experience in the technique of LA in more than 2600 patients spanning more than 30 years, along with modifications introduced. Additional prospective trials were also conducted. BP and HR were monitored during LA injection in 200 patients. The calculated operative time was compared between two groups of 21 patients each: the first group was operated upon under LA and the other under GA. Anesthesia time was calculated for LA with different adrenaline concentrations (1 : 20 000–1 : 200 000 and 0% or no adrenaline) by means of injections over both the mastoid and the forearm on five volunteers. Patient satisfaction was measured using postoperative questionnaire in 200 patients. Results Patients showed initial increase in BP due to apprehension, which was abolished with diazepam; a second increase in BP and HR occurred after LA injection by 3–10 min. LA statistically significantly shortened the operative time compared with GA. Time of anesthesia was longer using anesthetic solution with higher adrenaline concentration and was longer on the mastoid as compared with the forearm. Finally, 92% of the patients showed satisfaction from the procedure. Conclusion LA is a safe and effective way of anesthesia in ear surgery, allowing intraoperative testing of hearing, facial nerve action, and eustachian tube patency. With high adrenaline concentration, it allows excellent hemostasis, shortens the operative time, and increases the time of anesthesia, allowing probable prolonged postoperative analgesia and is well tolerated by the patients.

Enhanced activity of hormone sensitive lipase (HSL) in mesenteric but not epididymal fat correlates with higher production of epinephrine in mesenteric adipocytes in rat model of cachectic rheumatoid arthritis

Cachectic rheumatoid arthritis, the less frequent form of the disease, is associated with loss of fat mass and often more severe course of the disease. Its experimental model represents rat adjuvant arthritis (AA) characterized by edema, lack of appetite, sharp body weight and fat loss. As individual fat depots display functional differences, here we studied lipolytic activity and sensitivity to lipolytic stimuli of nodeless epididymal fat (eWAT) and perinodal mesenteric fat (mWAT) depots at the peak of AA. We also examined changes in catecholamine and cytokine levels involved in lipolysis in plasma and/or isolated adipocytes from both WATs to identify the contribution of local, adipocyte-based processes and/or systemic events to adiposity loss in cachectic rheumatoid arthritis. AA was induced to male Lewis rats by complete Freund’s adjuvant. Groups of ad libitum-fed and pair-fed controls were used to distinguish the effects of food restriction from inflammation-induced cachexia. Adipose triglyceride lipase (ATGL), hormone-sensitive lipase (HSL) and its phosphorylated form (pHSL) were analyzed by western blot. CRP and catecholamine levels in plasma or adipocyte lysates were determined using ELISA kits. Cytokine-induced neutrophil chemoattractant-1 (CINC-1/CXCL1), monocyte chemoattractant protein-1 (MCP-1/CCL2), IL-1β, IL-6, IL-10 and leptin in adipocyte lysate were analyzed by quantitative protein microarray. Plasma glycerol and FFA were measured spectrophotometrically. AA rats developed severe cachexia, with lower adiposity in mWAT compared to normal and pair-fed controls, whereas in eWAT the adiposity was similarly reduced in AA and pair-fed groups. ATGL levels in both WATs were not affected by AA or pair feeding. AA upregulated levels of HSL, pHSL and pHSL/HSL ratio in mWAT, whereas none of these parameters has changed in eWAT of AA rats or in either WATs of pair-fed rats. In AA rats plasma glycerol was elevated, whereas FFA concentration was reduced. Plasma norepinephrine and epinephrine were increased in AA compared with both groups of controls. In eWAT adipocytes, AA but not pair feeding, upregulated norepinephrine levels. In mWAT adipocytes, AA rats showed higher epinephrine levels than pair-fed controls. Leptin levels in both WATs were depleted in AA animals in accordance with body weight loss. None of the measured cytokines in eWAT and mWAT was enhanced. Our results demonstrate augmented lipolytic activity in mWAT and not eWAT during cachectic arthritis. The adipocyte-derived cytokines do not seem to contribute to activated lipolysis. We first demonstrated enhanced presence of norepinephrine in perinodal adipocytes that may contribute to the regulation of local lipolytic activity by auto/paracrine fashion and thus provide independent fuel supply to activated lymph nodes.

(437) - Vasoplegia After Heart Transplantation: Unraveling the Enigma

Vasoplegia (Vp) described as hypotension despite normal cardiac function, is not uncommon in the immediate post heart transplant (HTx) period. The cause of Vp is unknown but may be due to use of vasodilators prior to HTx, anesthesia, or presence of prior VADs. It has been reported that patients (pts) with continuous flow VADs may have greater Vp immediate after HTx. We sought to identify risk factors for the development of Vp. Between 2010-13 we assessed 244 HTx pts. Vp pts were defined as those with normal cardiac function by echo, normal cardiac index, yet within 48 hours of HTx also required intravenous pressors (vasopressin, norepinephrine or high dose epinephrine (>5mcg/min) for >24 hours to maintain mean arterial pressure >70 mmHg. Pts were divided into 3 groups: no Vp, mild Vp ( pts requiring 1 pressor), and moderate-severe Vp ( ≥2 pressors). 1-year survival, freedom from hemodialysis, freedom from infection and freedom from rejection were assessed. Risk factors for Vp, including presence of non-pulsatile VADs, use of multiple oral vasodilators prior to HTx, duration of anesthesia, presence of liver disease, and need for pre-HTx oral midodrine for hypotension, were retrospectively assessed. Vp was seen in 34.3% of pts post HTx,(74% was mild; 26% moderate-severe). Anesthesia time was significantly longer and incidence of pre-transplant midodrine use was significantly higher in the moderate-severe Vp group (table). There was a strong trend towards greater use of non-pulsatile VADs in moderate-severe Vp pts compared to mild Vp and non-Vp patients. Post-HTx 1-year survival, freedom from hemodialysis, rejection and infection were not significantly different between the three groups. Vp is common post HTx, but does not appear to adversely affect outcomes. Risk factors appear to include longer anesthesia time, need for midodrine pre-transplant and history of non-pulsatile VAD, which may disrupt autoregulatory vasoresponsiveness of blood vessels. Further studies involving larger cohorts are warranted.Tabled 1Outcome measureNo Vasoplegia (N=159)Mild Vasoplegia (N=63)Moderate-Severe Vasoplegia (N=22)p value1 Year Actuarial Survival91.5%90.5%83.5%0.5421 Year Freedom from Any Treated Rejection80.5%88.0%89.5%0.2731 Year Freedom from Treated ACR88.3%94.6%86.5%0.5021 Year Freedom from Treated AMR94.8%96.3%100.0%0.5141 Year Freedom from Treated BNR93.5%95.5%95.5%0.7571 Year Freedom from Hemodialysis93.5%89.3%90.5%0.6561 Year Freedom from Treated Infection80.2%72.9%69.6%0.559Potential risk factor for vasoplegiaNo Vasoplegia (N=159)Mild Vasoplegia (N=63)Moderate-Severe Vasoplegia (N=22)p valueLiver cirrhosis/fibrosis by ultrasound (%)5.7% (9)7.9% (5)18.2% (4)0.107Total Anesthesia Time in Minutes (Mean, SD)538.5, 188.7523.3, 127.4681.7, 256.70.002*Pre-transplant hypotension requiring midodrine (%)2.5% (4)3.2% (2)13.6% (3)0.033*≥ 3 oral vasodilators administered prior to transplant (%)30.8% (49)34.9% (22)31.8% (7)0.840MCS non-pulsatile device (%)12.6% (20)15.9 % (10)31.8% (7)0.061*P Open table in a new tab

Transforming Environmental Awareness of Students Through the Arts and Place-Based Pedagogies

Incorporating the Arts into immersive place-based education programs can increase connectivity with the environment and facilitate the development of socially responsible and pro-environmental learners. Increasingly, children and adolescents are alienated and detached from the natural world. Given this noticeable shift, educators working in the outdoor setting need to rethink their modus operandi. Past attempts to promote learner connection with the environment have centred upon short-term stays and risk-centric approaches that embrace high adrenaline activities. This is the antithesis of Touched By The Earth, a yearlong place-based enrichment program using multi-modal creative methods with young learners to delve into the impact of experiential learning and how the Arts promote a personal relationship with the environment.

Epinephrine increases contextual learning through activation of peripheral β2-adrenoceptors.

Phenylethanolamine-N-methyltransferase knockout (Pnmt-KO) mice are unable to synthesize epinephrine and display reduced contextual fear. However, the precise mechanism responsible for impaired contextual fear learning in these mice is unknown. Our aim was to study the mechanism of epinephrine-dependent contextual learning. Wild-type (WT) or Pnmt-KO (129x1/SvJ) mice were submitted to a fear conditioning test either in the absence or in the presence of epinephrine, isoprenaline (non-selective β-adrenoceptor agonist), fenoterol (selective β2-adrenoceptor agonist), epinephrine plus sotalol (non-selective β-adrenoceptor antagonist), and dobutamine (selective β1-adrenoceptor agonist). Catecholamines were separated by reverse-phase HPLC and quantified by electrochemical detection. Blood glucose was measured by coulometry. Re-exposure to shock context induced higher freezing in WT and Pnmt-KO mice treated with epinephrine and fenoterol than in mice treated with vehicle. In addition, freezing response in Pnmt-KO mice was much lower than in WT mice. Freezing induced by epinephrine was blocked by sotalol in Pnmt-KO mice. Epinephrine and fenoterol treatment restored glycemic response in Pnmt-KO mice. Re-exposure to shock context did not induce a significant difference in freezing in Pnmt-KO mice treated with dobutamine and vehicle. Aversive memories are best retained if moderately high plasma epinephrine concentrations occur at the same moment as the aversive stimulus. In addition, epinephrine increases context fear learning by acting on peripheral β2-adrenoceptors, which may induce high levels of blood glucose. Since glucose crosses the blood-brain barrier, it may enhance hippocampal-dependent contextual learning.

Stress-Induced In Vivo Recruitment of Human Cytotoxic Natural Killer Cells Favors Subsets with Distinct Receptor Profiles and Associates with Increased Epinephrine Levels.

BackgroundAcute stress drives a ‘high-alert’ response in the immune system. Psychoactive drugs induce distinct stress hormone profiles, offering a sought-after opportunity to dissect the in vivo immunological effects of acute stress in humans.Methods3,4-methylenedioxymethamphetamine (MDMA), methylphenidate (MPH), or both, were administered to healthy volunteers in a randomized, double-blind, placebo-controlled crossover-study. Lymphocyte subset frequencies, natural killer (NK) cell immune-phenotypes, and changes in effector function were assessed, and linked to stress hormone levels and expression of CD62L, CX3CR1, CD18, and stress hormone receptors on NK cells.ResultsMDMA/MPH > MDMA > MPH robustly induced an epinephrine-dominant stress response. Immunologically, rapid redistribution of peripheral blood lymphocyte-subsets towards phenotypically mature NK cells occurred. NK cytotoxicity was unaltered, but they expressed slightly reduced levels of the activating receptor NKG2D. Preferential circulation of mature NK cells was associated with high epinephrine receptor expression among this subset, as well as expression of integrin ligands previously linked to epinephrine-induced endothelial detachment.ConclusionThe acute epinephrine-induced stress response was characterized by rapid accumulation of mature and functional NK cells in the peripheral circulation. This is in line with studies using other acute stressors and supports the role of the acute stress response in rapidly mobilizing the innate immune system to counteract incoming threats.

Cardiac failure following inadvertent administration of high-dose epinephrine subcutaneously.

Our aim is to report the consequences of epinephrine toxicity leading to cardiac failure in a child and the successful management with dopamine and milrinone. A previously healthy 13-year-old girl undergoing a left tympanomastoidectomy was inadvertently administered 10 mL of 1:1000 epinephrine subcutaneously (0.175 mg/kg) on the left post auricular region in lieu of lidocaine. She developed sudden supraventricular tachycardia, hypertension and flash pulmonary edema. She was initially treated with propofol, nitrogycerin and increased peak end-expiratory pressure. Within 4 h, she remained tachycardic, but was hypotensive with an increased central venous pressure. Electrocardiogram and echocardiogram investigations showed ST changes indicative of myocardial ischemia and globally reduced function, respectively. Dopamine infusion was administered, together with milrinone, resulting in a gradual improvement of cardiac function within 3 days. She was transitioned to enalapril and discharged home. This case highlights the clinical features of high dose epinephrine toxicity secondary to iatrogenic subcutaneous overdose followed by hypotension and pulmonary edema as a possible late effect of epinephrine and the successful management of secondary cardiac failure with administration of dopamine, milrinone and enalapril.

Intoxication from Ferula sumbul leaves in a mother and her infant.

The genus Ferula comprises approximately 130 species that are distributed from the Mediterranean region to Central Asia. This genus is well documented as a source of biologically active compounds such as coumarins, terpene alcohols and sesquiterpene derivatives (1). Some of the isolated compounds of the dried roots of Ferula sumbul have anti-HIV activity and also demonstrate weak inhibition of cytokine release (1). Powder from F. sumbul roots are mixed with honey and used as aphrodisiac by men in some cultures (2). We report a case of a mother and her infant who over ingested F. sumbul leaves. To the best of our knowledge, this is the first report about intoxication with F. sumbul leaves in the literature. A 5-month-old female infant presented to our pediatric emergency department with the chief complaint of vomiting that started 2 hours after breastfeeding. Her mother also presented to the adult emergency department for vomiting. A thorough history revealed that F. sumbul leaves were harvested by mistake instead of green onion from the family garden. The mother, son and husband ate uncooked F. sumbul leaves. The Grandmother realized that the ingested plant was not green onion after the family had already consumed it. The mother began to vomit 2 hours after ingestion. Past medical histories of baby and mother were unremarkable. On physical examination of the baby, the vital findings were normal. Head circumference, body weight and height were within normal limits. No abnormal findings were noted on examination. Laboratory examination showed no abnormalities in complete blood count, serum electrolytes, coagulation parameters, renal and liver function tests. The infant was hospitalized and intravenous fluid was given for 2 hours. No medication was administered. Vomiting improved after a few hours without change in clinical status. Both the mother and infant were discharged home after 5 hours in emergency department. F. sumbul is a rich source of coumarin (1). Hepatotoxicity including elevated serum transaminases and hepatomegaly has been reported following coumarin treatment (4). In our case, there was no evidence of hepatotoxicity. Previous studies have also noted coumarins’MAO inhibiting effect (3). After oral administration coumarin is rapidly absorbed from the gastrointestinal tract and extensively metabolized by hepatic CYP2A6 to 7-hydroxycoumarin, which is excreted in the urine. The half-life for the elimination of coumarin is 1–2 hours in humans (4). We hypothesized that vomiting 2 hours after oral intake of F. sumbul is due to MAO-A inhibition causing high serotonin levels and stimulating 5HT3 receptors. MAO-A inhibition can also cause high norepinephrine and epinephrine levels, but we did not see significant adrenergic side effects in these patients (3). Other family members that ate F. sumbul leaves did not *Corresponding author: Dr. Hatice Derin, MD, Necmettin Erbakan University, Meram Medical Faculty, Department of Pediatrics, 42080 Meram, Konya, Turkey. Tel.: +90 332 223 75 46; Fax: +90 332 223 61 81 and +90 332 223 61 82. E-mail: haticederinkurt@gmail.com. Journal of Pediatric Intensive Care 2 (2013) 193–194 DOI 10.3233/PIC-13066 IOS Press 193

Exogenous Tryptophan Promotes Cutaneous Wound Healing of Chronically Stressed Mice through Inhibition of TNF-α and IDO Activation.

Stress prolongs the inflammatory response compromising the dermal reconstruction and wound closure. Acute stress-induced inflammation increases indoleamine 2, 3-dioxygenase-stimulated tryptophan catabolism. To investigate the role of indoleamine 2, 3-dioxygenase expression and tryptophan administration in adverse effects of stress on cutaneous wound healing, mice were submitted to chronic restraint stress and treated with tryptophan daily until euthanasia. Excisional lesions were created on each mouse and 5 or 7 days later, the lesions were analyzed. In addition, murine skin fibroblasts were exposed to elevated epinephrine levels plus tryptophan, and fibroblast activity was evaluated. Tryptophan administration reversed the reduction of the plasma tryptophan levels and the increase in the plasma normetanephrine levels induced by stress 5 and 7 days after wounding. Five days after wounding, stress-induced increase in the protein levels of tumor necrosis factor-α and indoleamine 2, 3-dioxygenase, and this was inhibited by tryptophan. Stress-induced increase in the lipid peroxidation and the amount of the neutrophils, macrophages and T cells number was reversed by tryptophan 5 days after wounding. Tryptophan administration inhibited the reduction of myofibroblast density, collagen deposition, re-epithelialization and wound contraction induced by stress 5 days after wounding. In dermal fibroblast culture, the tryptophan administration increased the cell migration and AKT phosphorylation in cells treated with high epinephrine levels. In conclusion, tryptophan-induced reduction of inflammatory response and indoleamine 2, 3-dioxygenase expression may have accelerated cutaneous wound healing of chronically stressed mice.

Renalase: Another puzzle piece between hypertension and simple renal cysts?

Since renalase is mostly expressed in kidney tubules, simple renal cyst (SRC) originates from the kidney tubules, and both conditions are related to hypertension, it may be possible that SRC is associated with increased renalase levels. Therefore, in the current study we aimed to confirm the relation between renalase and epinephrine levels, the association between SRC and renalase levels and the association between renalase, blood pressure levels and endothelial dysfunction. We made a cross-sectional study including 75 patients with SRC, and 51 controls were included to the study. Flow-mediated dilatation (FMD) was assessed, and serum renalase and epinephrine levels were determined. Patient with SRC had lower renalase, higher epinephrine and lower FMD levels when compared to patients without SRC (p < 0.05). Log renalase was correlated with log epinephrine (r = -0.302, p = 0.001) and log FMD (r = 0.642, p < 0.0001). There was no correlation between renalase and urine albumin/creatinine ratio and glomerular filtration rate. In univariate analysis, age, glomerular filtration rate, renalase and FMD were associated with the presence of SRC. Multivariate regression analysis of factors which are statistically significant in univariate analysis showed that age and renalase was associated with the presence of SRC. We have demonstrated that renalase levels were associated with the presence of SRC and endothelial dysfunction. Further research is necessary to highlight underlying mechanisms.

Infrared thermographic assessment of changes in skin temperature during hypoglycaemia in patients with type 1 diabetes.

Hypoglycaemia is associated with reduced skin temperature (Ts). We studied whether infrared thermography can detect Ts changes during hypoglycaemia in patients with type 1 diabetes and how the Ts response differs between patients with normal hypoglycaemia awareness and hypoglycaemia unawareness. Twenty-four patients with type 1 diabetes (ten aware, 14 unaware) were studied during normoglycaemia (5.0-6.0 mmol/l), hypoglycaemia (2.0-2.5 mmol/l) and during recovery from hypoglycaemia (5.0-6.0 mmol/l) using hyperinsulinaemic glucose clamping. During each 1 h phase, Ts was measured twice by infrared thermography imaging in pre-defined areas (nose, glabella and the five left fingertips), symptoms of hypoglycaemia were scored and blood was sampled. Ts decreased during hypoglycaemia on the nose and glabella. The highest decrements were recorded on the nose (aware: -2.6 °C, unaware: -1.1 °C). In aware patients, the differences in temperature were statistically significant on both nose and glabella, whereas there was only a trend in the unaware group. There was a significant difference in hypoglycaemia-induced temperature changes between the groups. Patients in the aware group had higher hypoglycaemia symptom scores and higher adrenaline (epinephrine) levels during hypoglycaemia. The hypoglycaemia-associated decrement in Ts can be assessed by infrared thermography and is larger in patients with normal hypoglycaemia awareness compared with unaware patients.

Renalase gene polymorphism and epinephrine level in chronic kidney disease.

Chronic kidney disease (CKD) is an important public health problem. Patients with end-stage renal disease have a significant renalase deficiency, which could be one of the mechanisms explaining high prevalence of hypertension in these patients. The aim of this study was to investigate the possible association of renalase gene (rs2296545) polymorphism with normotensive and hypertensive CKD in sampled Egyptian patients and to determine the effect of such polymorphism on epinephrine level. Renalase gene (rs2296545) polymorphism was genotyped in 178 patients with CKD (83 normotensive and 95 hypertensive nephrosclerosis) and 178 normal healthy adults using polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP). Epinephrine level was measured by HPLC method. We found an association of renalase (rs2296545) CC genotype and C allele with CKD. Also, the epinephrine level was significantly increased in normotensive and hypertensive nephrosclerosis patients as compared to controls. CKD patients with CC genotype showed significant high epinephrine level as compared to CG and GG genotypes.

Hypoglycemia-associated changes in the electroencephalogram in patients with type 1 diabetes and normal hypoglycemia awareness or unawareness.

Hypoglycemia is associated with increased activity in the low-frequency bands in the electroencephalogram (EEG). We investigated whether hypoglycemia awareness and unawareness are associated with different hypoglycemia-associated EEG changes in patients with type 1 diabetes. Twenty-four patients participated in the study: 10 with normal hypoglycemia awareness and 14 with hypoglycemia unawareness. The patients were studied at normoglycemia (5-6 mmol/L) and hypoglycemia (2.0-2.5 mmol/L), and during recovery (5-6 mmol/L) by hyperinsulinemic glucose clamp. During each 1-h period, EEG, cognitive function, and hypoglycemia symptom scores were recorded, and the counterregulatory hormonal response was measured. Quantitative EEG analysis showed that the absolute amplitude of the θ band and α-θ band up to doubled during hypoglycemia with no difference between the two groups. In the recovery period, the θ amplitude remained increased. Cognitive function declined equally during hypoglycemia in both groups and during recovery reaction time was still prolonged in a subset of tests. The aware group reported higher hypoglycemia symptom scores and had higher epinephrine and cortisol responses compared with the unaware group. In patients with type 1 diabetes, EEG changes and cognitive performance during hypoglycemia are not affected by awareness status during a single insulin-induced episode with hypoglycemia.