Epinephrine Infusion Research Articles

Activation of Sympathetic Nervous System Contributes to Erthroprotein Gene Upregulation by Hypobaric Hypoxia

Hypobaric hypoxia (HH) experienced at high altitude initiates a series of physiological adaptations to maintain homeostasis. One such adaptation is the activation of the Epo gene which encodes the glycoprotein hormone erythropoietin (EPO). Increased circulating EPO levels defend against HH by facilitating blood O2 transport through increasing red blood cell production. HH also increases blood pressure (BP) through activation of the sympathetic nervous system and the ensuing elevation of circulating catecholamine levels. The present study examined the role of sympathetic nerve activation in HH‐evoked Epo gene activation and elevated circulating levels of EPO. Studies were performed on adult, male wild‐type (WT) mice treated with 18 hours of HH (0.4 atmospheres), simulating low O2 condition experienced at high altitude. Our results showed increased renal Epo gene abundance and elevated plasma EPO levels. Remarkably, these responses were either markedly attenuated or absent in mice with selective ablation of adrenal medulla as well as after treatment with propranolol, a non‐selective beta‐adrenergic receptor blocker. Moreover, infusion of epinephrine alone activated renal Epo gene and elevated plasma EPO levels. These results suggest that sympathetic nerve activation and the ensuing increase in plasma epinephrine contribute to Epo gene activation by HH.

Establishing a multicenter, preclinical consortium in resuscitation: A pilot experimental trial evaluating epinephrine in cardiac arrest

BackgroundLarge animal studies are an important step in the translation pathway, but single laboratory experiments do not replicate the variability in patient populations. Our objective was to demonstrate the feasibility of performing a multicenter, preclinical, randomized, double-blinded, placebo-controlled cardiac arrest trial. We evaluated the effect of epinephrine on coronary perfusion pressure (CPP) as previous single laboratory studies have reported mixed results. MethodsForty-five swine from 5 different laboratories (Ann Arbor, MI; Baltimore, MD; Los Angeles, CA; Pittsburgh, PA; Toronto, ON) using a standard treatment protocol. Ventricular fibrillation was induced and left untreated for 6 min before starting continuous cardiopulmonary resuscitation (CPR). After 2 min of CPR, 9 animals from each lab were randomized to 1 of 3 interventions given over 12 minutes: (1) Continuous IV epinephrine infusion (0.00375 mg/kg/min) with placebo IV normal saline (NS) boluses every 4 min, (2) Continuous placebo IV NS infusion with IV epinephrine boluses (0.015 mg/kg) every 4 min or (3) Placebo IV NS for both infusion and boluses. The primary outcome was mean CPP during the 12 mins of drug therapy. ResultsThere were no significant differences in mean CPP between the three groups: 14.4 ± 6.8 mmHg (epinephrine Infusion), 16.9 ± 5.9 mmHg (epinephrine bolus), and 14.4 ± 5.5 mmHg (placebo) (p = NS). Sensitivity analysis demonstrated inter-laboratory variability in the magnitude of the treatment effect (p = 0.004). ConclusionThis study demonstrated the feasibility of performing a multicenter, preclinical, randomized, double-blinded cardiac arrest trials. Standard dose epinephrine by bolus or continuous infusion did not increase coronary perfusion pressure during CPR when compared to placebo.

P163 The cytokine horror: Kawasaki disease shock syndrome complicated with macrophage activation syndrome

Abstract Background/Aims Kawasaki disease (KD) is an acute febrile systemic vasculitis of unknown aetiology, affecting medium-sized vessels. It often occurs in children less than 5 years old. During the acute phase of the disease, less than 5% of children develop hypotension and shock. This severe form is called Kawasaki Disease Shock Syndrome (KDSS). Macrophage activation syndrome (MAS) is a heterogenous syndrome complex encompassing a broad spectrum of clinical features. MAS associated with KDSS is an extremely rare life threatening entity that warrants a high index of clinical suspicion, prompt and proper management. Methods We present our experience in the dilemmas and challenges faced in the diagnosis and management of KDSS complicated with MAS in a poor resource setting. It is our first experience of encountering MAS in KDSS. Results A 9-month-old baby with fever and a maculopapular rash involving palms and soles for 5 days duration was transferred from a peripheral hospital. A preliminary diagnosis of acute Kawasaki disease was made with the classical features that included the rash, cracked lips, pedal oedema, BCG scar inflammation, perianal excoriation and irritability. The fever did not settle following standard therapy that included three doses of intravenous immunoglobulins 2g/kg, aspirin and low dose dexamethasone. The child quickly began to decompensate. She developed cold clammy skin with hypotension on the 8th day of the illness. There was evidence of hepatosplenomegaly with transaminitis. 2D Echo revealed normal coronary vasculature without any dilatations or strictures. However, there was evidence of myocarditis supported by diffuse T inversions in the anterolateral leads and a highly positive troponin titre. Investigations revealed aa leucocytosis (22,100/dl), an abrupt drop in platelet count (350,000/dl to 80,000/dl), red blood cells, haemoglobin (11g/dl to 8g/dl) and erythrocyte sedimentation rate 95mm/hr to 50mm/hr. Hyperferritinemia, hypertriglyceridemia and hypofibrinogenemia supported the diagnosis of MAS. Blood culture was sterile. Initial bone marrow biopsy was inconclusive. High dose dexamethasone 10mg/m2/day and cyclosporine 2mg/kg/day was initiated. The circulatory collapse was managed with fluid boluses and a low dose adrenaline infusion. Subsequently there was dramatic clinical improvement and her cell counts and transaminases normalised on day 15. Conclusion We emphasise the importance of early recognition of refractory MAS in pediatric populations with rheumatic diseases and we suggest early initiation of cyclosporin as a rapid and effective treatment option in the poor resource settings where the ideal management with anakinra is beyond the realms of possibility. Disclosure L. Rajagopala: None. J. Jagoda: None. M.L. Gunatilaka: None.

Updating the CoFAR Grading Scale for Systemic Allergic Reactions in Food Allergy

Immunotherapy is promising as an efficacious treatment for food allergy. Other food allergy treatments are also under development. However, adverse allergic events during treatment, as well as during oral food challenges, are common and reporting is not standardized. A more nuanced grading scale is needed to create a comprehensive and universal system to categorize adverse events and their severity for food allergy clinical trials. Starting with the 2012 Consortium for Food Allergy Research (CoFAR) Grading Scale and the World Allergy Organization Grading System, we developed the CoFAR Grading Scale for Systemic Allergic Reactions, Version 3.0, in collaboration with industry partners with expert opinion. The revised CoFAR Grading Scale for Systemic Allergic Reactions has 5 levels of increasing severity, ranging from generalized urticaria, localized angioedema, rhinitis, and abdominal pain (grade 1) to death (grade 5). Systemic reactions are further categorized within each grade by relevant organ system. Mild, single-system reactions are differentiated from mild, multisystem reactions. Lower respiratory tract symptoms are graded on the basis of response to therapy; those that are refractory to standard treatment (eg, requiring >3 doses of intramuscular epinephrine, continuous intravenous epinephrine infusion, and continuous albuterol nebulization) and respiratory compromise requiring mechanical ventilation are classified as grade 4, life-threatening reactions. Universal and consistent use of the revised CoFARGrading Scale beyond the CoFAR centers would allow for better data aggregation and safety comparisons in clinicaltrials for food allergy.

First Asian Kidney Donor Profile Index (KDPI) and Estimated Post-Transplant Survival (EPTS) models, with validation against US models in Thai population.

Differences in transplant characteristics limit the application of kidney donor profile index (KDPI) and estimated post-transplant survival (EPTS) models developed in Western countries to Asian populations. We analyzed data of the Thai Transplant Registry and the Thai Red Cross Society on 2558 DDKTs performed between 2001 and 2014. Thai KDPI and EPTS models were developed using Cox regression, and validation against the US models. Thai KDPI was developed based on seven donor factors: age, height, best estimated glomerular filtration rate, diabetes mellitus, hypertension, cerebrovascular accident, and adrenaline infusion. The Thai and US donor risk index had comparable predictive abilities for transplant survival (C-statistics .5871vs. .5548; P=.429). KTs from donors with a US KDPI>70% demonstrated significantly worse 5-year transplant survival. The Thai EPTS model was developed from four recipient factors: age, body weight, diabetes mellitus, and hepatitis C infection. The C-statistics of the Thai and US EPTS models were comparable (.5924vs. .6039; P=.360). A US EPTS>70% was revealed in only 2.5% of our cohort. The first simplified KDPI and EPTS models for an Asian population were developed. Our models are available at www.thai-kdpi-epts.org.

Comparison of the efficacy of continuous intravenous infusion versus intramuscular injection of epinephrine for initial anaphylaxis treatment.

AimContinuous intravenous (CIV) infusion of epinephrine for the treatment of anaphylaxis may be required if symptoms do not improve after intramuscular (IM) injection. As CIV infusion permits precise dose adjustment, we compared treatment course and adverse events following CIV infusion and IM injection of epinephrine for the management of anaphylaxis.MethodsMedical records of patients, who were treated for anaphylaxis with epinephrine, were 18 years or older, and were admitted to our department from April 2005 to March 2016, were retrospectively reviewed. The cases were categorized as CIV infusion or IM injection, and treatment course and outcomes were compared between the two groups.ResultsOf the 142 eligible cases, there were 78 in the CIV infusion group and 64 in the IM injection group. The CIV infusion group had lower systolic blood pressure, more respiratory symptoms, and higher Acute Physiology and Chronic Health Evaluation II (APACHE II) scores, but required a lower total dose of epinephrine, had fewer adverse events after epinephrine administration, and showed lower incidence of biphasic reactions. In addition, compared with the IM injection group, time to administration of epinephrine was significantly longer (P < 0.001), but time to resolution of symptoms, both from contact and epinephrine administration, was significantly shorter (P < 0.01 and P = 0.03, respectively).ConclusionContinuous intravenous infusion of epinephrine for the treatment of anaphylaxis may be safe, has fewer adverse events, improves symptoms, and is relatively easy to administer under ready conditions. CIV infusion of epinephrine may also reduce the incidence of biphasic reactions.

Catecholamines are key modulators of ventricular repolarization patterns in the ball python (Python regius).

Ectothermic vertebrates experience daily changes in body temperature, and anecdotal observations suggest these changes affect ventricular repolarization such that the T-wave in the ECG changes polarity. Mammals, in contrast, can maintain stable body temperatures, and their ventricular repolarization is strongly modulated by changes in heart rate and by sympathetic nervous system activity. The aim of this study was to assess the role of body temperature, heart rate, and circulating catecholamines on local repolarization gradients in the ectothermic ball python (Python regius). We recorded body-surface electrocardiograms and performed open-chest high-resolution epicardial mapping while increasing body temperature in five pythons, in all of which there was a change in T-wave polarity. However, the vector of repolarization differed between individuals, and only a subset of leads revealed T-wave polarity change. RNA sequencing revealed regional differences related to adrenergic signaling. In one denervated and Ringer's solution-perfused heart, heating and elevated heart rates did not induce change in T-wave polarity, whereas noradrenaline did. Accordingly, electrocardiograms in eight awake pythons receiving intra-arterial infusion of the β-adrenergic receptor agonists adrenaline and isoproterenol revealed T-wave inversion in most individuals. Conversely, blocking the β-adrenergic receptors using propranolol prevented T-wave change during heating. Our findings indicate that changes in ventricular repolarization in ball pythons are caused by increased tone of the sympathetic nervous system, not by changes in temperature. Therefore, ventricular repolarization in both pythons and mammals is modulated by evolutionary conserved mechanisms involving catecholaminergic stimulation.

The cardioprotective effect of intralipid in decreasing the ischemic insults during off-pump coronary artery revascularization

BackgroundOff pump coronary artery revascularization (OPCAB) surgeries have benefits over the conventional on pump cardiac surgery, because it avoids the trauma caused by cardiopulmonary bypass (CPB) and minimize aortic manipulation. However, some disadvantages of OPCAB include the concern of ineffective coronary revascularization. Some drugs have shown the ability to protect the myocardium in different studies, by different methods. The usage of intralipid has been shown to make a better functional recovery of the cardiac muscles and help to decrease the myocardial infarct size, it shortens the action potential time, which show polyunsaturated fatty acids diets mechanism as an antiarrhythmic drug, and are associated with low incidence of coronary artery disease.MethodsWe divided patients into two groups according to the randomization envelopes: intralipid group (group A) received 1.5 ml/kg intralipid 20% through central venous line after sternotomy over 1 h and during infusion, blood pressure, heart rate, and temperature were monitored all through the infusion time. Control group (group B) received normal saline 0.9% in the same volume over the same duration.ResultsThis study showed that infusion of 1.5 ml/kg intralipid after sternotomy in off pump coronary artery revascularization given as preconditioning agent improve the myocardial ischemia reperfusion injury, decrease the need for high doses of nor adrenaline infusion after revascularization, earlier normalization in troponin levels starting 24 h after surgery and higher values of cardiac index were measured in ICU using PICCO.ConclusionsThis study showed the benefits of infusion of 1.5 ml/kg of intralipid after sternotomy, in preconditioning during OPCABG. Preconditioning with intralipid proved to decrease reperfusion injury in myocardium expressed by improvement in cardiac functions (EF and cardiac index) and normalization of specific cardiac marker (cardiac troponin I).

Clinical decision making in frequently encountered anomalous aortic origin of coronary arteries, the impact of IVUS

Abstract Introduction The aim in the diagnostic work-up of patients with an anomalous aortic origin of coronary arteries (AAOCA) is to determine whether the course of the coronary artery is benign or malignant. In patients with AAOCA with an interarterial course the guidelines on diagnostics are concise. Recommended CT-scan imaging does not evaluate stress-induced functional consequences like external compression by the pulmonary artery as the scan is performed in a resting state. Non-invasive ischemia detection techniques often lack sufficient sensitivity. To improve functional stratification, exploration of new diagnostic modalities in the diagnostic workup of AAOCA is mandatory. Purpose The purpose is to explore the potential role of intravascular ultrasound (IVUS) in the diagnostic workup of patients with AAOCA. Methods Nine patients with an anomalous right coronary artery with an interarterial course were analyzed. A cardiologist evaluated the complaints. Anatomical features of the AAOCA were assessed with CT-scan imaging. Further analyses included ischemia detection and coronary angiography. To assess stress-induced ischemia IVUS and invasive measurements – fractional flow reserve (FFR) and instantaneous wave-free ratio (iFR) – were performed at rest and during adrenaline-induced stress. A slit-like orifice was classified as a width/length (W/L) ratio of ≤0.50, an oval orifice as 0.51–0.9 and a round orifice as &amp;gt;0.91. Results Potential cardiac complaints were present in seven patients. In 8 (89%) patients CT-images showed an acute angle, in 8 (89%) proximal narrowing and an aortic take-off above the pulmonary valve in 4 (44%). In 7 (78%) patients a slit-like orifice and in two (22%) an oval orifice were observed (table 1). IVUS at rest showed a slit-like orifice in one patient classified as an oval orifice on the CT-images and vice versa in another patient (table 2). The patients classified as an oval orifice with IVUS showed no external compression during adrenaline-induced stress. In 4 (57%) out of 7 patients with an slit-like orifice on IVUS, the width remained unchanged or increased during adrenaline infusion. In 2 patients the width decreased slightly, however, these patients were asymptomatic and no ischemia was detected. In 1 (14%) patient the width remained 1.4mmm and the length increased from 3.2mm to 4.7mm. In this case the vessel ostium was fully engaged with the IVUS catheter, hence, the width could not decrease during adrenaline infusion. This was regarded as external compression. In addition, in this patient ischemia was detected. Conclusion(s) In two (22%) out of 9 patients IVUS gave a better insight of the shape of the orifice than CT. Additionally, the anatomic and functional-dynamic components of compression could be defined with adrenaline-induced stress. Therefore, IVUS can contribute to a better understanding of the functional consequences of the anatomical features and of potential stress-induced external compression. Funding Acknowledgement Type of funding sources: None. Table 1Table 2

Comparison of Efficacy between Sildenafil Alone and Sildenafil with Milrinone for Treatment of Persistent Pulmonary Hypertension of the Newborn

Introduction: In persistent pulmonary hypertension of the newborn (PPHN), some neonates do not response to single pulmonary vasodilator drug, so recently combination therapy is being tried to decrease pulmonary artery systolic pressure (PASP). The aim of the study was to compare the efficacy of oral sildenafil alone with combination of oral sildenafil and milrinone in neonates suffering from PPHN. Methods: This RCT study was conducted in Dhaka Shishu (Children) Hospital, from July 2018 to June 2020. Sixty eight (68) term and near term neonates aged &lt;10 days (34 cases in each group) with moderate to severe PPHN were taken. Monotherapy with oral sildenafil was given in group-A and combined therapy with oral sildenafil and i/v milrinone in Group-B. Serial echocardiography was done at before starting the therapy, at 3 days and at 5 days of treatment. Data regarding baseline characteristics, clinical features, PASP, PO2, Spo2, hospital stay, mortality and others investigations were recorded and analyzed with SPSS version-26. Results: Post treatment PASP was significantly reduced in group A (sildenafil) and group-B (sildenafil plus milrinone) (p&lt;0.05). But in combination group PASP was more reduced than monotherapy group (p&lt;0.05). Within the group, the oxygen saturation and PO2 significantly improved in both groups (p&lt;0.05) but no significant difference was found in between two groups (p&gt;0.05). Adrenaline infusion, hypotension and less hospital stay were significantly seen (P&lt;0.05) in combination group. Conclusion: Combined therapy with oral sildenafil and milrinone are more effective than monotherapy with oral sildenafil in reduction of PASP. Both therapies are effective in improvement of oxygenation.

Metabolic and behavior responses of lactating goats under heat stress

Heat stress (HS) negatively affects animal performance, but little is known about energetic metabolism and behavior changes in dairy goats under HS conditions. Eight multiparous Murciano-Granadina dairy goats (43.3 ± 1.6 kg BW; 2 ± 0.04 L milk/d; 81 ± 3 days of lactation) were kept in metabolism cages and randomly assigned to two treatments varying in the temperature humidity index (THI). The design was crossover (two 28-d periods), and treatments were: 1) thermal neutral (TN; 15–20C, 40–45% humidity, THI = 59–65), and 2) heat stress (HS, 12 h/d at 37°C and 40%, and 12 h/d at 30°C and 40%, THI = 86 and 77, respectively). Jugular silicon catheters were fitted, and glucose tolerance test (0.25 g/kg BW), insulin tolerance test (4.6 μg/kg BW) and epinephrine challenge (2 μg/kg BW) were conducted. Before and after each metabolite administration, blood samples were collected for the analysis of insulin, glucose, and nonesterified fatty acids (NEFA). Also, behavior variables (position changes, duration of remaining standing, as well as eating and drinking bouts and duration) were observed at day 3 of each period by video cameras. Heat stress reduced (P < 0.01) feed intake (−29%), milk yield (−10%), milk fat (–12%), milk protein (–14%), and milk casein (–13%). Goats in both groups had similar blood NEFA after insulin administration, but NEFA values were greater (P < 0.05) in TN than HS goats after epinephrine infusion. The HS goats secreted lower (P < 0.05) amounts of insulin than TN goats in response to the glucose tolerance test. Additionally, TN and HS goats had similar number of eating bouts, but the duration of each bout was shorter in HS than in TN. Also, HS had greater number of drinking bouts with no differences in drinking bout durations between groups. In conclusion, body lipid tissue of HS goats became more resistant to lipolysis, making them unable to mobilize body fat reserves despite the negative energy balance. In addition, the reduction in feed intake by HS was because of the shorter time of eating bouts, whereas the greater water consumption was related to the increase in drinking bouts.

EXTRACORPOREAL MEMBRANE OXYGENATION MODALITY DETERMINED BY POINT-OF-CARE ULTRASOUND IN A PATIENT WITH AMLODIPINE OVERDOSE: A CASE REPORT

TOPIC: Critical Care TYPE: Medical Student/Resident Case Reports INTRODUCTION: The use of calcium channel blockers (CCB) as first-line antihypertensive therapy has correlated with increased incidences of CCB overdose. Massive CCB overdose proves difficult to manage as patients are prone to refractory distributive shock and noncardiogenic pulmonary edema. Extracorporeal membrane oxygenation (ECMO) has been a successful rescue therapy in CCB overdose. Veno-arterial (VA) ECMO has been the traditional modality used as it provides both cardiac and pulmonary support. However, recent case reports have described successful use of veno-venous (VV) ECMO for CCB overdose when cardiac function is preserved. We present a case of amlodipine overdose where VV ECMO was used instead of VA ECMO. This decision was guided by a point of care ultrasound (POCUS) exam that demonstrated a hyperdynamic left ventricle (LV) and normal right ventricle (RV) function immediately prior to cannulation. The patient subsequently improved, was decannulated, and survived to hospital discharge. CASE PRESENTATION: A 52-year-old male intentionally overdosed with amlodipine (750mg total). Emergency medical services were notified and transported the patient to the nearest critical access hospital. The patient became hypoxic, developed multipressor shock and met criteria for severe acute respiratory distress syndrome. On hospital day two the patient remained hypoxic despite an FiO2 of 1.0, deep sedation, neuromuscular blockade (NMB) and prone positioning. His shock was refractory despite infusions of norepinephrine, epinephrine, vasopressin and phenylephrine in addition to stress dose steroids and methylene blue. Our ECMO team was consulted for intervention. Prior to cannulation, cardiac POCUS revealed a hyperdynamic LV and preserved RV function. This guided our decision to implement VV instead of VA ECMO. The patient was cannulated then transported to our tertiary care institution. On ECMO day 2, the patient came off epinephrine and phenylephrine and NMB was discontinued. On ECMO day 4, the patient remained on norepinephrine alone and followed simple commands during a sedation holiday. On ECMO day 7 the patient no longer required vasopressors and was decannulated. The patient underwent tracheostomy placement, was placed on a long-term ventilator wean and discharged on hospital day 21. DISCUSSION: CCB overdose leading to refractory shock presents a difficult challenge for clinicians. There is promising data regarding the use of VA ECMO and, recently, VV ECMO as a rescue treatment in addition to supportive critical care in these cases. Selection of the appropriate ECMO modality prior to cannulation is paramount to optimize cardiopulmonary support. CONCLUSIONS: We assert that this case demonstrates the potential for utilizing POCUS as a tool to help decide what ECMO modality to use in patients with CCB overdose. Further study into POCUS as a means of determining ECMO modality is warranted. REFERENCE #1: Fadhlillah F, Patil S. Pharmacological and mechanical management of calcium channel blocker toxicity. BMJ Case Rep. 2018;2018:bcr2018225324. Published 2018 Aug 27. doi:10.1136/bcr-2018-225324 REFERENCE #2: Haughey R, Vernick W, Gutsche J, Laudanski K. Use of veno-venous extracorporeal membrane oxygenation to treat severe combined calcium channel blocker and angiotensin converting enzyme inhibitor overdose. Perfusion. 2019 Mar;34(2):167-169. doi: 10.1177/0267659118798181. Epub 2018 Sep 3. PMID: 30175658. REFERENCE #3: Lindeman E, Ålebring J, Johansson A, Ahlner J, Kugelberg FC, Nordmark Grass J. The unknown known: non-cardiogenic pulmonary edema in amlodipine poisoning, a cohort study. Clin Toxicol (Phila). 2020 Nov;58(11):1042-1049. doi: 10.1080/15563650.2020.1725034. Epub 2020 Mar 2. PMID: 32114860. DISCLOSURES: No relevant relationships by Jonathon Davis, source=Web Response No relevant relationships by Jon Greenberg, source=Web Response No relevant relationships by Logan Rosenberg, source=Web Response

LIPID EMULSION THERAPY FOR LIFE-THREATENING FLECAINIDE TOXICITY

TOPIC: Critical Care TYPE: Medical Student/Resident Case Reports INTRODUCTION: We present a case of flecainide (FLC) toxicity secondary to renal failure treated with intravenous lipid emulsion (ILE) therapy. CASE PRESENTATION: The patient is a 63 year old female with a history of stage IVB uterine carcinosarcoma, chronic kidney disease and supraventricular tachycardia (SVT) on FLC. She was admitted with intra-abdominal hemorrhagic metastases. A rapid response was called due to hypotension, and she was noted to be oliguric for the previous 24 hours with a serum creatinine 2.5 mg/dL (baseline 1.3 mg/dL) and hyponatremic (126 mmol/L). EKG showed a new wide complex rhythm, at 78bpm, QRS widening to 280ms, and prolonged QTc of 631. She subsequently suffered a wide complex tachyarrhythmic cardiac arrest (CA), refractory to two shocks, with return of spontaneous circulation after treatment with sodium bicarbonate (NaHCO3). FLC was discontinued and the patient was started on a hypertonic NaHCO3 drip, but frequent NaHCO3 pushes were required to correct widening of the QRS complex. The hypotension progressed requiring high dose infusions of epinephrine (15 mcg/min) and norepinephrine (90 mcg/min). ILE infusion was started, 20% lipid 1.5 mL/kg administered over 5 minutes, followed by an infusion of 0.25 mL/kg/minute over two hours. A serum FLC level was drawn during ILE infusion and came back elevated at 1.35 mcg/mL (therapeutic level 0.20-1.0 mcg/mL). In the 48 hours following ILE, there was resolution of the wide complex arrhythmias, and vasopressor requirements were reduced by more than 50% DISCUSSION: FLC is a class 1C antiarrhythmic that inhibits Na+ channels and is used for prevention of SVT. It has a narrow therapeutic range and about 30% is renally excreted making acute kidney injury a risk for toxicity. Other risk factors for toxicity are hyponatremia and hypokalemia. Characteristic signs of toxicity include hypotension, lethargy and EKG changes such as QRS widening and PR prolongation. These changes can progress to wide complex brady or tachyarrhythmic CA as seen in our patient. Standard of care is administration of hypertonic NaHCO3 which acts both as a Na+ load to compete with FLC for binding at Na+ channels and as an alkalinizing agent which decreases the ionized receptor-binding form of FLC. However, when NaHCO3 treatment fails, there are few other well studied options. One is VA-ECMO for which our patient was not a candidate. The other is lipid emulsion therapy, which is hypothesized to work by creating a lipid sink to sequester the drug and also has some positive ionotropy. CONCLUSIONS: In our patient, administration of ILE resulted in significant clinical improvement. Unfortunately, the clinical improvement did not sustain after several days and due to overall poor prognosis, the patient was eventually transitioned to comfort measures. REFERENCE #1: Subedi R, Dean R, Chaudhary A. Flecainide toxicity in renal failure. Proc (Bayl Univ Med Cent). 2018 May 9;3(3):328-330. REFERENCE #2: Ghataoura R, Patil S. Flecainide toxicity: a presentation to the emergency department with literature review. BMJ Case Rep. 2020 Feb 28;13(2):e232691. doi: 10.1136/bcr-2019-232691. PMID: 32114494; PMCID: PMC7050315. REFERENCE #3: Valentino MA, Panakos A, Ragupathi L, Williams J, Pavri BB. Flecainide Toxicity: A Case Report and Systematic Review of its Electrocardiographic Patterns and Management. Cardiovasc Toxicol. 2017 Jul;17(3):260-266. doi: 10.1007/s12012-016-9380-0. PMID: 27435408. DISCLOSURES: No relevant relationships by Rebecca Fieles, source=Web Response No relevant relationships by David Gerber, source=Web Response No relevant relationships by Brian Park, source=Web Response No relevant relationships by Harry Rockower, source=Web Response No relevant relationships by Diana Solomon, source=Web Response No relevant relationships by Yanika Wolfe, source=Web Response

SUCCESSFUL MANAGEMENT OF SOTALOL OVERDOSE IN THE ICU: UTILIZATION OF EARLY TEMPORARY IV PACING AND HEMODYALISIS

TOPIC: Critical Care TYPE: Medical Student/Resident Case Reports INTRODUCTION: Sotalol is a non-selective beta blocker with class III antiarrhythmic properties, a bioavailability of 90-100%, negligible protein binding, low lipid solubility, and 80-90% renal excretion. Sotalol toxicity is a medical emergency associated with hemodynamic instability and fatal arrhythmias. There are no standardized management guidelines with literature suggesting the use of IV glucagon, calcium, bicarbonate, high dose insulin infusion, lipid emulsion therapy and hemodialysis (HD). We report a case of Sotalol toxicity with significant cardiac instability successfully managed with conventional therapy in conjunction with early utilization of temporary pacing and HD. CASE PRESENTATION: 29-year-old female with history of thyroidectomy and drug abuse presented to the emergency department at 15:00 after ingesting 60 tablets of Sotalol 80mg in a suicide attempt. IV Glucagon and calcium were administered on scene. On arrival, she was bradycardic, hypotensive, with a QTc of 495 and serum sotalol concentration (SCC) of 11374ng/ml. Dextrose 10% and insulin infusion at 25units/hr were started for stabilization, up-titration was limited due to glucose disturbance. At 17:00 she required an Epinephrine infusion at 0.04mcg/hr for hemodynamic support, bicarbonate infusion, IV Mg, calcium gluconate and atropine. At 18:34 QTc increased to 683, patient was taken for prompt placement of temporary pacer with a set rate of 45bpm. Nephrology was consulted for emergent HD despite a normal kidney function to help with drug clearance. HD was initiated at 00:30 but was stopped after 2.5 hours due to hypotension and Torsades de Pointes (TdP). Insulin and Epinephrine drips were increased to 45units/hr and 0.24mcg/hr, pacing was increased to 50bpm, 2g of IV Mg were given with subsequent resolution of TdP. At 5:30, she had another episode of NSVT for which she received IV Mg. She required up to 0.5mcg/hr of Epinephrine for stabilization. On day 2 SSC was reduced to 6916ng/mL. At 1600, recurrent NSVT was noted, over-ride pacing was set at 90bpm, she underwent an additional 4 hours of HD. On day 3 she had a 3rd session 4-hour-HD with a post SCC of 401ng/mL. Temporary Pacer was removed on day 4. She had no recurrent arrhythmias and was successfully weaned off insulin and epinephrine drips. Repeat Sotalol levels remained <120ng/mL. DISCUSSION: Large dose Sotalol overdose is rarely encountered and carries significant risk to patients due to its QT prolonging effect associated with TdP, ventricular arrhythmias, and cases reporting asystole requiring cardiopulmonary resuscitation. Our patient was successfully managed without major complications or end-organ damage with early utilization of a temporary pacemaker and HD in addition to conventional therapy. CONCLUSIONS: It is plausible that early external pacing and HD played a role in avoiding adverse outcomes and should be considered in future cases of sotalol toxicity. REFERENCE #1: Anderson JL, Askins JC, Gilbert EM, et al. Multicenter trial of sotalol for suppression of frequent, complex ventricular arrhythmias: a double-blind, randomized, placebo-controlled evaluation of two doses. J Am Coll Cardiol. 1986;8(4):752-762. doi:10.1016/s0735-1097(86)80414-4 DISCLOSURES: No relevant relationships by Anil Kumar Ananthaneni, source=Web Response No relevant relationships by Cory Markham, source=Web Response No relevant relationships by Malak Modi, source=Web Response No relevant relationships by Nasim Motayar, source=Web Response No relevant relationships by Axel Rodriguez Rosa, source=Web Response

Cardiovascular Effects of Epinephrine During Experimental Hypothermia (32°C) With Spontaneous Circulation in an Intact Porcine Model

Aims: Rewarming from accidental hypothermia and therapeutic temperature management could be complicated by cardiac dysfunction. Although pharmacologic support is often applied when rewarming these patients, updated treatment recommendations are lacking. There is an underlying deficiency of clinical and experimental data to support such interventions and this prevents the development of clinical guidelines. Accordingly, we explored the clinical effects of epinephrine during hypothermic conditions.Materials and methods: Anesthetized pigs were immersion cooled to 32°C. Predetermined variables were compared at temperature/time-point baseline, after receiving 30 ng/kg/min and 90 ng/kg/min epinephrine infusions: (1) before and during hypothermia at 32°C, and after rewarming to 38°C (n = 7) and (2) a time-matched (5 h) normothermic control group (n = 5).Results: At 32°C, both stroke volume and cardiac output were elevated after 30 ng/kg/min administration, while systemic vascular resistance was reduced after 90 ng/kg/min. Epinephrine infusion did not alter blood flow in observed organs, except small intestine flow, and global O2 extraction rate was significantly reduced in response to 90 ng/kg/min infusion. Electrocardiographic measurements were unaffected by epinephrine infusion.Conclusion: Administration of both 30 ng/kg/min and 90 ng/kg/min at 32°C had a positive inotropic effect and reduced afterload. We found no evidence of increased pro-arrhythmic activity after epinephrine infusion in hypothermic pigs. Our experiment therefore suggests that β₁-receptor stimulation with epinephrine could be a favorable strategy for providing cardiovascular support in hypothermic patients, at core temperatures >32°C.

Comparing Risk Profiles in Critical Care Patients With Stage 2 and Deep Tissue Pressure Injuries: Exploratory Retrospective Cohort Study.

Understanding hospital-acquired pressure injury (HAPrI) etiology is essential for developing effective preventive interventions. Pressure injuries are classified based on the degree of visible tissue damage; the two most commonly identified HAPrI stages in critical care patients are stage 2 and deep tissue injury (DTI). Some experts speculate that stage 2 and DTI have different etiologies, with stage 2 injuries formed from the "outside in" as a result of tissue deformation, decreased perfusion, and subsequent ischemia caused by external pressure and/or shear forces, whereas DTI emerges from the "inside out" due to inadequate perfusion to the deeper tissues causing tissue ischemia. The purpose of this study was to compare risk profiles of intensive care unit (ICU) patients who developed stage 2 injuries versus DTIs. This was a retrospective cohort study to compare the risk profiles of patients in the ICU with stage 2 injuries and DTIs using electronic health record data. Eligible patients were admitted to the surgical or cardiovascular ICU at an academic medical center in the United States between 2014 and 2018. Anatomic locations were examined, and differences in anatomic patterns were compared using the χ2 test. Risk profile variables included demographic characteristics, Braden Scale scores, vasopressor infusions, hypotension, surgical factors, length of stay, BMI, laboratory values, diabetes, Charlson Comorbidity Index, and the levels of sedation or agitation. The distributions of potential risk variables between patients with stage 2 injuries and DTIs were summarized and compared. A logistic regression model with the least absolute shrinkage and selection operator method was developed to identify the critical risk factors for distinguishing stage 2 and DTI patients. A total of 244 patients developed a stage 2 injury or DTI during the study period. Of those, 38 patients with medical device-related pressure injury were excluded. The final study sample consisted of 206 patients (n=146 stage 2 and n=60 DTI). Compared with DTIs, stage 2 HAPrIs were more likely to be located on a bony prominence (n=206, χ21=8.43, P=.03). The multivariate model showed that patients who developed stage 2 HAPrIs had a longer length of stay in the ICU than those with DTIs (odds ratio [OR] 1.001, 95% CI 1-1.002, P=.03) but were less likely than patients with DTIs to experience a diastolic blood pressure <50 mmHg (OR 0.179, 95% CI 0.072-0.416, P<.001) or receive an epinephrine infusion (OR 0.316, 95% CI 0.079-0.525, P=.008). Stage 2 injuries and DTIs have different risk factors and different anatomic patterns. Patients who developed DTIs were more likely to experience low diastolic blood pressure and receive epinephrine, a potent vasopressor. Stage 2 injuries were more likely to occur on the bony prominences, whereas DTIs commonly occurred on the fleshy parts of the body such as the buttock.

Anesthetic Management for Combined Cardiac and Renal Transplantation: a Case Report

Cardiac and renal diseases are related physiologically and often co-exist in patients with either one disease. The population of patients with end-stage cardiac and renal diseases is growing, and the waiting lists for one or both organ transplantation continue to grow. Here, we describe the case of performing general anesthesia for combined heart and kidney transplantation. A 55-year-old male who has underlying diabetes mellitus, chronic kidney failure and heart failure was referred for combined heart and kidney transplantation. After the induction of general anesthesia, heart transplantation was done. Norepinephrine, epinephrine, and dobutamine infusions were initiated for the weaning from cardiopulmonary bypass. After heart transplantation, continuous renal replacement therapy was used in operation room. Kidney transplantation was done and the patient was sent to intensive care unit without extubation. The patient was discharged to general ward on postoperative day 6 after extubation. Since more patients require multi-organ transplantation, it is important for anesthesiologist to understand the physiology of underlying disease and the process of operation. Keywords: Anesthetics, Inhalation, Heart-kidney transplantation, Hemodialysis

The effect of using the minimized cardio-pulmonary bypass Systems for Coronary Artery Bypass Grafting in diabetic patients

IntroductionMultiple studies have shown a decrease in the inflammatory response with minimized bypass circuits leading to less complications and mortality rate. On the other hand, some other studies showed that there is no difference in post-operative outcomes. So, the aim of this study is to investigate the clinical benefits of using the Minimized cardiopulmonary Bypass system in Coronary Artery Bypass Grafting and its effect on postoperative morbidity and mortality in diabetic patients as one of the high-risk groups that may benefit from these systems.MethodsThis is a retrospective study that included 114 diabetic patients who underwent Coronary artery bypass grafting (67 patients with conventional cardiopulmonary bypass system and 47 with Minimized cardiopulmonary bypass system). The patients’ demographics, intra-operative characteristics and postoperative complications were compared between the two groups.ResultsCoronary artery bypass grafting was done on a beating heart less commonly in the conventional cardiopulmonary bypass group (44.78% vs. 63.83%, p = 0.045). There was no difference between the two groups in blood loss or transfusion requirements. Four patients in the conventional cardiopulmonary bypass group suffered perioperative myocardial infarction while no one had perioperative myocardial infarction in the Minimized cardiopulmonary bypass group. On the other hand, less patients in the conventional group had postoperative Atrial Fibrillation (4.55% vs. 27.5%, p = 0.001). The requirements for Adrenaline and Nor-Adrenaline infusions were more common the conventional group than the Minimized group.ConclusionThe use of conventional cardiopulmonary bypass for Coronary Artery Bypass Grafting in diabetic patients was associated with higher use of postoperative vasogenic and inotropic support. However, that did not translate into higher complications rate or mortality.

Incidence, characteristics and risk factors for perioperative cardiac arrest and 30-day-mortality in preterm infants requiring non-cardiac surgery

Study objectiveTo determine 30-day-mortality, incidence and characteristics of perioperative cardiac arrest as well as the respective independent risk factors in preterm infants undergoing non-cardiac surgery. DesignRetrospective observational Follow-up-study. SettingBielefeld University Hospital, a German tertiary care hospital. PatientsPopulation of 229 preterm infants (age < 37th gestational week at the time of surgery) who underwent non-cardiac surgery between 01/2008–12/2018. MeasurementsPrimary endpoint was overall 30-day-mortality. Secondary endpoints were the incidence of perioperative cardiac arrest and identification of independent risk factors. We performed univariate and multivariate analyses and calculated odds ratios (OR) for risk factors associated with these endpoints. Main results30-day-mortality was 10.9% and perioperative mortality 0.9%. Univariate risk factors for 30-day-mortality were perioperative cardiac arrest (OR,12.5;95%CI,3.1 to 50.3), comorbidities of lungs (OR,3.7;95%CI,1.2 to 11.3) and gastrointestinal tract (OR,3.5;95%CI,1.3 to 9.6); sepsis (OR,3.6;95%CI,1.4 to 9.5); surgery between 22:01–7:00 (OR,7.3;95%CI,2.4 to 21.7); emergency (OR,4.5;95%CI,1.6 to 12.4); pre-existing catecholamine therapy (OR,5.0;95%CI,2.1 to 11.9). Multivariate logistic regression indicated that perioperative cardiac arrest (OR,13.9;95%CI,2.7 to 71.3), low body weight (weight < 1000 g: OR,26.0;95%CI,3.2 to 212; 1000-1499 g: OR,10.3; 95%CI,1.1 to 94.9 compared to weight > 2000 g), and time of surgery (OR,5.9;95%CI,1.6 to 21.3) for 22:01–7:00 compared to 7:01–15:00) were the major independent risk factors of mortality. Incidence of perioperative cardiac arrests was 3.9% (9 of 229;95%CI,1.8 to 7.3). Univariate risk factors were congenital anomalies of the airways (OR,4.7;95%CI,1.2 to 20.3), lungs (OR,4.7;95%CI,1.2 to 20.3) and heart (OR,8.0;95%CI,2 to 32.2), pre-existing catecholamine therapy (OR,59.5;95%CI,3.4 to 1039), specifically, continuous infusions of epinephrine (OR,432;95%CI,43.2 to 4318). Conclusions30-day-mortality and the incidence of perioperative cardiac arrest of preterms undergoing non-cardiac surgery were higher than previously reported. The identified independent risk factors may improve interdisciplinary perioperative risk assessment, optimal preoperative stabilization and scheduling of optimal surgical timing.

Early Resuscitation in Paediatric Sepsis Using Inotropes – A Randomised Controlled Pilot Study in the Emergency Department (RESPOND ED): Study Protocol and Analysis Plan

Introduction: Septic shock in children still carries substantial mortality and morbidity. While resuscitation with 40–60 mL/kg intravenous fluid boluses remains a cornerstone of initial resuscitation, an increasing body of evidence indicates potential for harm related to high volume fluid administration. We hypothesize that a protocol on early use of inotropes in children with septic shock is feasible and will lead to less fluid bolus use compared to standard fluid resuscitation. Here, we describe the protocol of the Early Resuscitation in Paediatric Sepsis Using Inotropes – A Randomised Controlled Pilot Study in the Emergency Department (RESPOND ED).Methods and analysis: The RESPOND ED study is an open label randomised controlled, two arm, multicentre pilot study conducted at four specialised paediatric Emergency Departments. Forty children aged between 28 days and 18 years treated for presumed septic shock will be randomized in a 1:1 ratio to early inotropes vs. standard fluid resuscitation. Early inotrope treatment is defined as the commencement of a continuous intravenous adrenaline infusion after 20 mL/kg fluid bolus resuscitation. Standard fluid resuscitation is defined as delivery of 40 to 60 mL/kg fluid bolus resuscitation prior to commencement of inotropes. In addition to feasibility outcomes, survival free of organ dysfunction censored at 28 days will be assessed as the main clinical outcome. The study cohort will be followed up at 28 days, and at 6 months post enrolment to assess quality of life and functional status. Biobanking nested in the study cohort will be performed to enable ancillary biomarker studies.Ethics and dissemination: The trial has ethical clearance (Children's Health Queensland, Brisbane, HREC/18/QCHQ/49168) and is registered in the Australian New Zealand Clinical Trials Registry (ACTRN12619000828123). Enrolment commenced on July 21st, 2019. The primary manuscript will be submitted for publication in a peer-reviewed journal.Trial Registration: Australian and New Zealand Clinical Trials Registry, ACTRN12619000828123.