High-dose Epinephrine Research Articles

(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

Acute kidney injury after cardiac arrest.

IntroductionThe aim of this study was to evaluate the incidence and determinants of AKI in a large cohort of cardiac arrest patients.MethodsWe reviewed all patients admitted, for at least 48 hours, to our Dept. of Intensive Care after CA between January 2008 and October 2012. AKI was defined as oligo-anuria (daily urine output <0.5 ml/kg/h) and/or an increase in serum creatinine (≥0.3 mg/dl from admission value within 48 hours or a 1.5 time from baseline level). Demographics, comorbidities, CA details, and ICU interventions were recorded. Neurological outcome was assessed at 3 months using the Cerebral Performance Category scale (CPC 1–2 = favorable outcome; 3–5 = poor outcome).ResultsA total of 199 patients were included, 85 (43%) of whom developed AKI during the ICU stay. Independent predictors of AKI development were older age, chronic renal disease, higher dose of epinephrine, in-hospital CA, presence of shock during the ICU stay, a low creatinine clearance (CrCl) on admission and a high cumulative fluid balance at 48 hours. Patients with AKI had higher hospital mortality (55/85 vs. 57/114, p = 0.04), but AKI was not an independent predictor of poor 3-month neurological outcome.ConclusionsAKI occurred in more than 40% of patients after CA. These patients had more severe hemodynamic impairment and needed more aggressive ICU therapy; however the development of AKI did not influence neurological recovery.

Activity of antioxidant enzymes and gelatinase in rats with epinephrine-induced miocardial ischemia

&lt;p&gt;In this study we examined the activity of antioxidant enzymes and gelatinases in rats with epinephrine-induced&lt;br /&gt;myocardial ischemia and the impact of corvitin (C) and doxycycline (D) on these indicators. The administration&lt;br /&gt;of epinephrine (0.2 mg/100 g) for 10 days leads to an increase in lipid peroxidation and to the elevated activity of&lt;br /&gt;antioxidant enzymes and gelatinases in blood and in the heart of experimental animals. Under application of C and&lt;br /&gt;D activity of the enzymes was reduced, especially activity of SOD and gelatinases. Our data suggest that C and D&lt;br /&gt;can reduce the cardiotoxic effects of high doses of epinephrine due to their ability to bind free radicals and to inhibit&lt;br /&gt;the activity of matrix-degrading enzymes.&lt;/p&gt;

Myocardial protection induced by fentanyl in pigs exposed to high-dose adrenaline.

The use of high doses of adrenaline is common in critical patients, especially during cardiac arrest. During these situations, myocardial dysfunction can be a result of multiple factors, including adrenaline use. In addition, opioids have been shown to have anti-arrhythmic and anti-ischemic mechanisms that may confer cardiac protection. This study aimed to evaluate the effects of fentanyl on myocardial function in pigs exposed to high-dose adrenaline. After institutional ethics committee approval, 26 pigs were randomly allocated to receive either 20 μg/kg fentanyl (n = 10; fentanyl group) administered 5 min before five doses of adrenaline (20 μg/kg), equivalent-volume saline (n = 10; saline group) using the same adrenaline dosing protocol, or neither fentanyl nor adrenaline (n = 6; sham group). The fentanyl group showed lower levels of troponin at the end of the sixth hour compared with the saline group (1.91 ± 1.47 vs 5.44 ± 5.35 ng/mL, P = 0.019). Transmission electron microscopy and immunohistochemistry also showed less myocardial injury in the fentanyl group. The conclusion was reached that fentanyl attenuates myocardial injury caused by high-dose adrenaline without blunting the hemodynamic effect of adrenaline.

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.

Experimental study of taurine antitoxic activity in the model of chronic epinephrine intoxication.

AbstractEmotional stress causes a lot of diseases due to release of high doses of epinephrine in the blood. Further epinephrine oxidizes to adrenochrome with formation of the superoxide radical, which is very active and can cause apoptosis. Therefore, a targeted search of new active compounds that could protect organisms from free radicals is a perspective line of development of new ischemia-reperfusion injury correctors and cardio-vascular drugs. We decided to investigate taurine—a well-known endogenic antioxidant and membrane protector - during chronic epinephrine intoxication in rats. Our experiments have shown that therapeutic administration of taurine reduced cerebral metabolic disorders and prevented cerebral lipid peroxidation during chronic epinephrine intoxication.KeywordsTaurineChronic epinephrine intoxicationAdrenochromeAdrenaline

Use of esmolol after failure of standard cardiopulmonary resuscitation to treat patients with refractory ventricular fibrillation

IntroductionWe compare the outcomes for patients who received esmolol to those who did not receive esmolol during refractory ventricular fibrillation (RVF) in the emergency department (ED). MethodsA retrospective investigation in an urban academic ED of patients between January 2011 and January 2014 of patients with out-of-hospital or ED cardiac arrest (CA) with an initial rhythm of ventricular fibrillation (VF) or ventricular tachycardia (VT) who received at least three defibrillation attempts, 300mg of amiodarone, and 3mg of adrenaline, and who remained in CA upon ED arrival. Patients who received esmolol during CA were compared to those who did not. Results90 patients had CA with an initial rhythm of VF or VT; 65 patients were excluded, leaving 25 for analysis. Six patients received esmolol during cardiac arrest, and nineteen did not. All patients had ventricular dysrhythmias refractory to many defibrillation attempts, including defibrillation after administration of standard ACLS medications. Most received high doses of adrenaline, amiodarone, and sodium bicarbonate. Comparing the patients that received esmolol to those that did not: 67% and 42% had temporary return of spontaneous circulation (ROSC); 67% and 32% had sustained ROSC; 66% and 32% survived to intensive care unit admission; 50% and 16% survived to hospital discharge; and 50% and 11% survived to discharge with a favorable neurologic outcome, respectively. ConclusionBeta-blockade should be considered in patients with RVF in the ED prior to cessation of resuscitative efforts.

Takotsubo-like left ventricular dysfuction following intravenous epinephrine administration

A 50-year old woman presented at her general practitioner following facial swelling due to an insect bite. She was treated with 100 mg Solucortef and 1 mg epinephrine of a 1: 10 000 solution intravenously. Minutes later she developed chest pain with concomitant non-specific changes in the electrocardiogram (ECG), and later significant Troponin I concentrations were demonstrated. She was treated with anticoagulants, and later a bedside echocardiography revealed reduced left ventricular ejection fraction and apical ballooning pattern as seen in Takotsubo Cardiomyopathy. During hospitalization the patient had an episode of Torsade’s de pointes ventricular tachycardia and several unexplained cerebral absences. Coronary angiography revealed normal coronary arteries, and the patient exhibited normal ejection fraction one month after hospital discharge. Physicians should avoid giving high doses of epinephrine by the intravenous route and only in cases of severe anaphylaxis

Could the survival and outcome benefit of adrenaline also be dependent upon the presence of gasping upon arrival of emergency rescuers?

A recent systematic review and meta-analysis of randomized controlled trials of adrenaline use during resuscitation of out-of-hospital cardiac arrest found no benefit of adrenaline in survival to discharge or neurological outcomes. It did, however, find an advantage of standard dose adrenaline (SDA) over placebo and high dose adrenaline over SDA in overall survival to admission and return of spontaneous circulation (ROSC), which was also consistent with previous reviews. As a result, the question that remains is "Why is there no difference in the rate of survival to discharge when there are increased rates of ROSC and survival to admission in patients who receive adrenaline?" It was suggested that the lack of efficacy and effectiveness of adrenaline may be confounded by the quality of cardiopulmonary resuscitation (CPR) during cardiac arrest, which has been demonstrated in animal models. CPR quality was not measured or reported in the included randomized controlled trials. However, the survival and outcome benefit of adrenaline may also depend upon the presence of witnessed gasping and/or gasping upon arrival of emergency rescuers, which is a critical factor not accounted for in the analyses of the cited animal studies that allowed gasping but showed the survival and neurological outcome benefits of adrenaline use. Moreover, without the aid of gasping, very few rescuers can provide high-quality CPR. Also, age and the absence of gasping observed by bystanders and/or upon arrival of emergency- rescuers may be important factors in the determination of whether vasopressin instead of adrenaline should be used first.

Émulsions lipidiques intraveineuses et toxicité systémique des anesthésiques locaux : mécanismes et limites

ObjectivesIntravenous lipid emulsions (ILE) are recommended today in cases of local anesthetic-induced systemic toxicity (LAST). The objectives of this review consists in describing mechanisms involved in the interaction between ILE and local anesthetic (LA) factors influencing this interaction and the limits associated with the use of ILE. Data sourcesReferences were obtained from Pubmed data bank (http://www.ncbi.nlm.nih.gov/pubmed) using the following keywords: Intralipid®, local anesthetic, toxicity, intravenous lipid emulsion. Data synthesisEffects of the association between ILE-LA are based on droplet formations as well as changes in cell metabolism involving survival cell pathway, on functional properties and on direct hemodynamic parameters. Hypoxia, acidosis and high doses of epinephrine modified the effects of ILE-LA association. ConclusionPrescription of ILE is recommended by published guidelines on LAST resuscitation. ILE cannot substitute to the standard resuscitation protocol. It should be added to that protocol. Experimental studies as well as a case report registry will allow understanding further the effects induced by the ILE-LA association.

Epinephrine May Be of No Survival Benefit in Cardiac Arrest

Standard advanced cardiac life support guidelines recommend administration of epinephrine at a dose of 1 mg every 3 to 5 minutes, but is there evidence that this therapy improves outcomes? To answer this question, researchers performed a meta-analysis of 14 randomized, controlled trials (12,250 total patients) in nine countries that compared standard-dose epinephrine with high-dose epinephrine (>1 mg per dose), vasopressin, or placebo in …

Vasopressin improves survival compared with epinephrine in a neonatal piglet model of asphyxial cardiac arrest

Epinephrine is a component of all resuscitation algorithms. Vasopressin is a pulmonary vasodilator and systemic vasopressor. We investigated the effect of epinephrine vs. vasopressin on survival and hemodynamics after neonatal porcine cardiac arrest (CA). A 4-min asphyxial CA was induced, after which cardiopulmonary resuscitation (CPR) was commenced. Animals were randomized to low- (LDE: 0.01 mg/kg) or high-dose epinephrine (HDE: 0.03 mg/kg), low- (LDV: 0.2 U/kg) or high-dose vasopressin (HDV: 0.4 U/kg), or control (saline). Clinical and echocardiography indexes were monitored. Sixty-nine animals were randomized. Survival was greater in HDV (n = 8 (89%); P < 0.05 ANOVA) vs. control (n = 7 (43%)) and LDE (n = 5 (36%)) but not vs. HDE (n = 7 (64%)) or LDV (n = 6 (75%)). Animals resuscitated with LDE required more shocks (2.5 (interquartile range: 2-6); P < 0.05) and higher doses of energy (15 J (interquartile range: 10-20); P < 0.05). Left ventricular output was comparable between groups, but a greater increase in superior vena caval flow was seen after HDV (P < 0.001 vs. control, LDE, and HDE). Plasma troponin was greatest in the HDE group (P < 0.05 vs. control and HDV). Vasopressin results in improved survival, lower postresuscitation troponin, and less hemodynamic compromise after CA in newborn piglets. Vasopressin may be a candidate for testing in human neonates.

Intraoperative High-Dose Epinephrine Infiltration in Cleft Palate Repair

Local infiltration of epinephrine before surgical procedures is a well-accepted technique to promote vasoconstriction. Typically, the dose of epinephrine is limited by the co-administration of local anesthetic as well as the risk for arrhythmogenesis and hemodynamic changes. In addition, some controversy exists regarding the acceptable dose of epinephrine given to children. This retrospective review examines the use and safety of "high-dose" epinephrine in palatoplasty at our cleft-craniofacial center. A retrospective review of epinephrine use in primary palatoplasty at a tertiary children's hospital from 2003 to 2007 was performed. Operative and anesthetic records were reviewed for hypertension (systolic blood pressure, >120 or diastolic blood pressure, >70) and tachycardia (>190 beats per min) as defined by the American Heart Association guidelines, as well as dysrhythmias, intraoperative complications, and postoperative complications. A total of 102 patients who underwent consecutive primary palatoplasties performed by a single surgeon were identified. After the induction of anesthesia and before incision, the patients received an initial epinephrine infiltration (without local anesthetic) up to a maximum 10 μg/kg. The average total dose of epinephrine administered during palatoplasty was 12.8 μg/kg (range, 3.2-75.0 μg/kg). Doses up to a maximum of 10 μg/kg were administered as needed at 30-minute intervals. No instances of clinically unstable tachycardia or hypertension occurred. A total of 21.6% of the patients (22/102) experienced an instance of hypertension, and only 13.7% of these (14/102) were related to epinephrine administration. One (1%) postoperative fistula was identified. Locally infiltrated high-dose epinephrine during palatoplasty can be safely used as a means of vasoconstriction. Doses reaching a maximum of 10 μg/kg, administered as needed at 30-minute intervals, do not seem to be a significant risk for hemodynamic instability, intraoperative complications, or postoperative complications.

Coronary Perfusion Pressure Response to High-Dose Intraosseous versus Standard-Dose Intravenous Epinephrine Administration after Prolonged Cardiac Arrest

Background: This study was done to compare coronary perfusion pressure (CPP) prior to the first rescue shock (RS) among a group of animals that received intraosseous (IO) epinephrine 0.1 mg/ kg (high-dose epinephrine [HDE]) with a group that received intravenous (IV) epinephrine 0.01 mg/kg (standard-dose epinephrine [SDE]) during cardiac arrest resuscitation using a swine model of prolonged out-of-hospital ventricular fibrillation (VF) cardiac arrest. Methods: This was a secondary analysis of prospectively collected data from two IACUC approved protocols. Seventy-nine Yorkshire swine (25 - 35 kg) were surgically instrumented under anesthesia and VF was electrically induced. After 10 minutes of untreated VF in the IO study (n = 26) and 12 minutes of untreated VF in the IV study (n = 53), resuscitation commenced with closed chest compressions (CCC). A single dose of epinephrine (HDE IO or SDE IV, respectively) was given and flushed with saline. The CCC and RS attempts were standardized for all animals. The CPP was defined as aortic diastolic pressure minus right atrial diastolic pressure measured 2.5 minutes after medication delivery. Descriptive statistics were used to analyze the data. Results: Baseline group characteristics were mathematically the same. Just prior to the first RS, HDE IO resulted in a mean CPP of 33.2 mmHg (95%CI: 26.6, 39.9), while SDE IV resulted in a mean CPP of 25.0 mmHg (95%CI: 20.5, 29.4). Conclusion: This observation study reaffirms the assertion that HDE IO may be required to generate CPP values similar to SDE IV during resuscitation of prolonged VF.

Sugammadex Hypersensitivity—A Case of Anaphylaxis

We describe a case of a patient undergoing open abdominal aneurysm surgery who developed a severe, life-threatening allergic reaction immediately after administration of sugammadex. The manifestation was purely a cardiovascular collapse. The mainstay of treatment was administration of high-dose adrenaline and fluid resuscitation. The diagnosis of anaphylaxis was supported by a positive serum mast cell tryptase (93 µg/l) at one hour post-event. Sugammadex was confirmed as the cause of the anaphylaxis by a positive intradermal allergy test (25 mm diameter response to 1:100 dilution), with a normal saline control and a negative response to the other drugs used during the event. This case report is a reminder that the use of sugammadex is associated with rare but serious risks.

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Introduction: Twenty-one-month old female with past medical history of egg allergy, presented to our hospital emergency room with perioral rash, emesis, cough, and generalized itching. One hour prior to admission she had meat loaf (containing milk, eggs). Child was given an antihistaminic medication and brought to emergency room. In the emergency room, patient received three doses of epinephrine 0.01mg/kg (1:1000 concentration; one dose IM and two doses IV) and racemic epinephrine nebulization over a period of twenty minutes for respiratory distress. Work of breathing continued to get worse and she became hypotensive. Three normal saline boluses of 20ml/kg each were given for hypotension and she was started on epinephrine drip at 1 mcg/kg/min in the emergency room before transferring the child to PICU. In PICU, the child had increased work of breathing, tachycardia (180-200 bpm) and poor peripheral perfusion. Child was intubated in the PICU and was placed on mechanical ventilator. She started developing pink frothy secretions. X-ray chest was consistent with pulmonary edema. EKG showed sinus tachycardia with nonspecific ST T wave changes and an echocardiogram revealed depressed left ventricular systolic function with an ejection fraction of 44%. Initial troponin (3.2 ng per ml), CPK-MB (11.5 ng per ml) and beta type natriuretic peptide (5000 pg per ml) levels were elevated. She was started on milrinone and lasix drips and epinephrine drip was weaned off. Over the next ten days, serial echocardiograms showed improvement in cardiac function with a final ejection fraction of 69% and normalization of cardiac enzymes. Child was discharged home fourteen days after admission. Discussion: Children with severe anaphylaxis may present with non-cardiogenic pulmonary edema and vasodilatory shock. However, in our patient clinical status worsened after starting epinephrine therapy and her cardiac enzymes were elevated along with cardiac dysfunction suggesting myocardial injury. As the child improved once the epinephrine was stopped catecholamine induced cardiomyopathy is a distinct possibility. Epinephrine is the cornerstone of anaphylaxis treatment. However, it has a narrow therapeutic index and can results in serious side effects. It is known that high dose of epinephrine administration can cause myocardial stunning and global myocardial hypokinesis. Diffuse myocardial injury was observed in experimental studies with excessive catecholamines. Such changes are also seen in patients with catecholamine excess states like, pheochromocytoma, stress induced cardiomyopathy (Tako-tsubo cardiomyopathy), and neurogenic myocardial stunning. This child was managed with ventilatory support, milrinone infusion and discontinuation of epinephrine. In refractory cases ECMO may be needed as a temporary support. Catecholamine induced cardiomyopathy is reversible within days to weeks. Caution should be exercised giving multiple doses of epinephrine for the management of anaphylaxis. Catecholamine induced cardiomyopathy should be considered in a child with poor cardiac function and high dose of epinephrine.

Bleeding control in endoscopic sinus surgery: a systematic review of the literature

In the literature various methods are described to reduce bleeding in endoscopic sinus surgery. Scientific evidence and results were gathered and analysed to determine the effectiveness of the various methods used. A total of 20 articles fulfilled the inclusion criteria. Two retrospective articles studied the differences between local and general anaesthesia. Three articles analysed the use of local methods to control bleeding. The majority of the articles analysed the use of different systemic drugs to control intraoperative bleeding. Certain procedures, such as the reverse Trendelenburg position, the use of high doses of epinephrine, the infiltration of phenylephrine and lidocaine into the pterygopalatine fossa, the preoperative use of prednisone, and the control of the heart rate (with dexmedetomidine or remifentanil), appear to reduce the intraoperative blood loss and/or improve the visualisation of the surgical field. However, the evidence supporting these conclusions is poor. The benefits of other procedures, such as the preoperative use of β-blockers, antihypertensive agents, and surgical pledgets with oxymetazoline, phenylephrine, or cocaine, for bleeding control are not evidenced in the literature. In addition, the literature does not present any evidence on the benefits of local anaesthesia compared with general anaesthesia or the use of propofol compared to inhaled analgesics in terms of intraoperative bleeding or complication rates.

Recruitment of GABAA receptors and fearfulness in chicks: Modulation by systemic insulin and/or epinephrine

One-day-old chicks were individually assessed on their latency to peck pebbles, and categorized as low latency (LL) or high latency (HL) according to fear. Interactions between acute stress and systemic insulin and epinephrine on GABAA receptor density in the forebrain were studied. At 10days of life, LL and HL chicks were intraperitoneally injected with insulin, epinephrine or saline, and immediately after stressed by partial water immersion for 15min and killed by decapitation. Forebrains were dissected and the GABAA receptor density was measured ex vivo by the 3[H]-flunitrazepam binding assay in synaptosomes. In non-stressed chicks, insulin (non-hypoglycemic dose) at 2.50IU/kg of body weight incremented the Bmax by 40.53% in the HL chicks compared to saline group whereas no significant differences were observed between individuals in the LL subpopulation. Additionally, insulin increased the Bmax (23.48%) in the HL group with respect to the LL ones, indicating that the insulin responses were different according to the anxiety of each category. Epinephrine administration (0.25 and 0.50mg/kg) incremented the Bmax in non-stressed chicks, in the LL group by about 37% and 33%, respectively, compared to ones injected with saline. In the stressed chicks, 0.25mg/kg bw epinephrine increased the Bmax significantly in the HL group by about 24% compared to saline, suggesting that the effect of epinephrine was only observed in the HL group under acute stress conditions. Similarly, the same epinephrine doses co-administered with insulin increased the receptor density in both subpopulations and also showed that the highest dose of epinephrine did not further increase the maximum density of GABAAR in HL chicks. These results suggest that systemic epinephrine, perhaps by evoking central norepinephrine release, modulated the increase in the forebrain GABAA receptor recruitment induced by both insulin and stress in different ways depending on the subpopulation fearfulness.

Bleeding control in endoscopic sinus surgery: a systematic review of the literature

In the literature various methods are described to reduce bleeding in endoscopic sinus surgery. Scientific evidence and results were gathered and analysed to determine the effectiveness of the various methods used. A total of 20 articles fulfilled the inclusion criteria. Two retrospective articles studied the differences between local and general anaesthesia. Three articles analysed the use of local methods to control bleeding. The majority of the articles analysed the use of different systemic drugs to control intraoperative bleeding. Certain procedures, such as the reverse Trendelenburg position, the use of high doses of epinephrine, the infiltration of phenylephrine and lidocaine into the pterygopalatine fossa, the preoperative use of prednisone, and the control of the heart rate (with dexmedetomidine or remifentanil), appear to reduce the intraoperative blood loss and/or improve the visualisation of the surgical field. However, the evidence supporting these conclusions is poor. The benefits of other procedures, such as the preoperative use of β-blockers, antihypertensive agents, and surgical pledgets with oxymetazoline, phenylephrine, or cocaine, for bleeding control are not evidenced in the literature. In addition, the literature does not present any evidence on the benefits of local anaesthesia compared with general anaesthesia or the use of propofol compared to inhaled analgesics in terms of intraoperative bleeding or complication rates.

High Levels of Circulating Epinephrine Trigger Apical Cardiodepression in a β 2 -Adrenergic Receptor/G i –Dependent Manner

Background— Takotsubo cardiomyopathy is an acute heart failure syndrome characterized by myocardial hypocontractility from the mid left ventricle to the apex. It is precipitated by extreme stress and can be triggered by intravenous catecholamine administration, particularly epinephrine. Despite its grave presentation, Takotsubo cardiomyopathy is rapidly reversible, with generally good prognosis. We hypothesized that this represents switching of epinephrine signaling through the pleiotropic β 2 -adrenergic receptor (β 2 AR) from canonical stimulatory G-protein–activated cardiostimulant to inhibitory G-protein–activated cardiodepressant pathways. Methods and Results— We describe an in vivo rat model in which a high intravenous epinephrine, but not norepinephrine, bolus produces the characteristic reversible apical depression of myocardial contraction coupled with basal hypercontractility. The effect is prevented via G i inactivation by pertussis toxin pretreatment. β 2 AR number and functional responses were greater in isolated apical cardiomyocytes than in basal cardiomyocytes, which confirmed the higher apical sensitivity and response to circulating epinephrine. In vitro studies demonstrated high-dose epinephrine can induce direct cardiomyocyte cardiodepression and cardioprotection in a β 2 AR-Gi–dependent manner. Preventing epinephrine-G i effects increased mortality in the Takotsubo model, whereas β-blockers that activate β 2 AR-G i exacerbated the epinephrine-dependent negative inotropic effects without further deaths. In contrast, levosimendan rescued the acute cardiac dysfunction without increased mortality. Conclusions— We suggest that biased agonism of epinephrine for β 2 AR-G s at low concentrations and for G i at high concentrations underpins the acute apical cardiodepression observed in Takotsubo cardiomyopathy, with an apical-basal gradient in β 2 ARs explaining the differential regional responses. We suggest this epinephrine-specific β 2 AR-G i signaling may have evolved as a cardioprotective strategy to limit catecholamine-induced myocardial toxicity during acute stress.