Epinephrine Infusion Research Articles

Adrenaline Auto-Injectors for Preventing Fatal Anaphylaxis.

Anaphylaxis affects up to 5% of people during their lifetime. Although anaphylaxis usually resolves without long-term physical consequences, it can result in anxiety and quality of life impairment. Rarely and unpredictably, community anaphylaxis can cause rapid physiological decompensation and death. Adrenaline (epinephrine) is the cornerstone of anaphylaxis treatment, and provision of adrenaline autoinjectors (AAI) has become a standard of care for people at risk of anaphylaxis in the community. In this article, we explore the effectiveness of AAIs for preventing fatal outcomes in anaphylaxis, using information drawn from animal and human invivo studies and epidemiology. We find that data support the effectiveness of intravenous adrenaline infusions for reversing physiological features of anaphylaxis, typically at doses from 0.05 to 0.5 μg/kg/min for 1-2 h, or ~ 10 μg/kg total dose. Intramuscular injection of doses approximating 10 μg/kg in humans can result in similar peak plasma adrenaline levels to intravenous infusions, at 100-500 pg/mL. However, these levels are typically short-lived following intramuscular adrenaline, and pharmacokinetic and pharmacodynamic outcomes can be unpredictable. Epidemiological data do not support an association between increasing AAI prescriptions and reduced fatal anaphylaxis, although carriage and activation rates remain low. Taken together, these data suggest that current AAIs have little impact on rates of fatal anaphylaxis, perhaps due to a lack of sustained and sufficient plasma adrenaline concentration. Effects of AAI prescription on quality of life may be variable. There is a need to consider alternatives, which can safely deliver a sustained adrenaline infusion via an appropriate route.

Adrenaline bolus rescue for refractory carcinoid crises during surgical manipulation of metastatic neuroendocrine tumor of pancreas: A case report

Carcinoid crisis is a potentially fatal condition with severe hemodynamic instability. A 25-year-old female with metastatic pancreatic neuroendocrine tumor with recurrent carcinoid crises was posted for surgical debulking. Intraoperatively, the patient was on crisis during manipulation of the lesion by the surgeon, which was unresponsive to octreotide, infusions of phenylephrine, and norepinephrine agents. The patient was then effectively managed with adrenaline blouses at 10 µg along with infusion of adrenaline. Use of inotropes and vasopressors is not encouraged in carcinoid due to release of inflammatory mediators which can precipitate the hemodynamic instability. Here, we managed her with adrenaline boluses and infusion.

Pre-hospital 'dirty adrenaline': A descriptive case series of patients receiving peripheral dilute adrenaline infusions in Central Australian remote nurse-led clinics prior to aeromedical retrieval.

'Dirty adrenaline' is the informal term used for a rapidly made peripheral dilute adrenaline infusion in the emergency treatment of shock, most commonly 1 mg adrenaline in 1 L 0.9% NaCl. It has long been part of the remote clinician's arsenal despite no supporting scientific literature. Remote clinics in Central Australia can be hours away from critical care support. The region's high prevalence of renal and cardiac disease means that access to early vasopressors and inotropes is a necessity for treating shock. To tackle this, remote clinicians often use 'dirty adrenaline'. We present a review of 'dirty adrenaline' use in this region. Central Australian Retrieval Service's database was screened to identify cases in which a peripheral dilute adrenaline infusion was administered in a remote clinic prior to patient aeromedical retrieval. A retrospective chart review collected: patient demographics; clinical characteristics; infusion details; adverse events; hospital lengths of stay; and mortality outcomes. Fifty-seven cases were identified. Median patient age was 50 (range: 2-96). Septic shock was the most common clinical indication (40/57). Median infusion duration was 155 min. Median systolic BP from commencement until retrieval increased from 75.5 to 91 mmHg. Survival to hospital discharge was 86% (49/57). No significant adverse events associated with 'dirty adrenaline' were recorded. 'Dirty adrenaline' is safe to administer and appears to considerably improve survival when used to treat fluid-resistant shock in remote nurse-led clinics guided by an off-site critical care physician.

In a Canine Model of Septic Shock, Cardiomyopathy Occurs Independent of Catecholamine Surges and Cardiac Microvascular Ischemia.

High levels of catecholamines are cardiotoxic and associated with stress-induced cardiomyopathies. Using a septic shock model that reproduces the reversible cardiomyopathy seen over 10 days associated with human septic shock, we investigated the effects of catecholamines on microcirculatory perfusion and cardiac dysfunction. Purpose-bred beagles received intrabronchial Staphylococcus aureus (n=30) or saline (n=6). The septic animals were than randomized to epinephrine (1 μg/kg per minute, n=15) or saline (n=15) infusions from 4 to 44 hours. Serial cardiac magnetic resonance imaging, catecholamine levels, and troponins were collected over 92 hours. Serial adenosine-stress perfusion cardiac magnetic resonance imaging was performed on septic animals randomized to receive saline (n=8 out of 15) or epinephrine (n=8 out of 15). High-dose sedation was given to suppress endogenous catecholamine release. Despite catecholamine levels largely remaining within the normal range throughout, by 48 hours, septic animals receiving saline versus nonseptic animals still developed significant worsening of left ventricular ejection fraction, circumferential strain, and ventricular-aortic coupling. In septic animals that received epinephrine versus saline infusions, plasma epinephrine levels increased 800-fold, but epinephrine produced no significant further worsening of left ventricular ejection fraction, circumferential strain, or ventricular-aortic coupling. Septic animals receiving saline had a significant increase in microcirculatory reserve without troponin elevations. Septic animals receiving epinephrine had decreased edema, blunted microcirculatory perfusion, and elevated troponin levels that persisted for hours after the epinephrine infusion stopped. Cardiac dysfunction during sepsis is not primarily due to elevated endogenous or exogenous catecholamines nor due to decreased microvascular perfusion-induced ischemia. However, epinephrine itself has potentially harmful long-lasting ischemic effects during sepsis including impaired cardiac microvascular perfusion that persists after stopping the infusion.

Adrenaline intravenous therapy persistence grade I severe allergic reaction: A case report and literature review.

At present, there is still insufficient understanding of the progression from persistent allergic reactions to severe reactions. Adrenaline remains the preferred medication for severe allergic reactions, and intramuscular injection of adrenaline can also be considered for patients with grade I reactions that are difficult to alleviate gastrointestinal symptoms. It is worth further discussing whether it is possible to break the conventional intramuscular injection recommended by the guidelines when the effect of intramuscular injection is not ideal for persistent grade I severe allergic reactions. A young male, 20 years of age, was admitted to emergency department because of repeated rash for 3 days and abdominal pain for 6 hours after taking traditional Chinese medicine. After hormone therapy, the rash continued to recur and secondary gastrointestinal symptoms occurred on the 3th day. Adrenaline intramuscular injection was given to temporarily relieve the rash and abdominal pain, but symptoms still persisted. The patient was diagnosed with persistent severe allergic reaction (grade I). Continuous intravenous infusion of low-dose adrenaline under electrocardiographic monitoring, real-time monitoring of heart rate and blood pressure, and routine treatment with methylprednisolone, diphenhydramine, calcium gluconate, and cetirizine. During this period, adrenaline intramuscular injection is temporarily added when abdominal pain symptoms are obvious. The entire treatment process used a total of 6.8 mg of adrenaline. During the entire period of adrenaline intervention, the patient did not experience any new discomfort, and there were no abnormal fluctuations in heart rate, rhythm, or blood pressure. The symptoms of rash and abdominal pain gradually improved. For patients with persistent grade I severe allergic reactions, intravenous administration of low-dose adrenaline under close vital sign monitoring is safe, feasible, and highly effective in preventing biphasic, persistent, or worsening allergic reactions.

Experiencia en DAC cardiaca en la Comunidad Valenciana: programa de extracción cardiaca extrahospitalaria

IntroductionIn Spain, since 2020, hearts obtained from donation after circulatory determination of death (DCD) have been used for heart transplants. We show our experience from the beginning of the heart DCDs program. An out-of-hospital cardiac extraction protocol has been implemented within the Valencian Community. Materials and methodFrom November 2022 to April 2024, 21 cardiac assessments have been performed in the context of DCD.Donor inclusion criteria: donor <55years old; family donation consent; functional warm ischemia time <30min.Donor exclusion criteria, additional to those of a cardiac donation: adrenaline infusion; dobutamine infusion; norepinephrine infusion >0,3μg/kg/min.This is a retrospective descriptive study. ResultsOf the 21 possible donors, 19 were valid hearts, 2 of them were for a hospital outside the community. The mean age of the donors was 40.4years, most of them men. In total, 17 patients were transplanted in our hospital. The mean cardiac ischemia time was 136.41min. Primary graft failure was described in 8 patients. ConclusionsThe cardiopulmonary bypass allowed continuous monitoring of aerobic and anaerobic metabolism, correct emptying of the cardiac chambers and the administration of cardioplegia with pressure, temperature and flow control.Our experience highlights the possibilities of success with hearts obtained from a DCD, representing an increase in the number of donors and a decrease in the waiting time for the transplant.

Severe anaphylaxis requiring continuous adrenaline infusion during oral food challenge: A case series

Severe anaphylaxis requiring continuous adrenaline infusion during oral food challenge: A case series

Dexmedetomidine for Reducing Mortality in Patients With Septic Shock A Randomized Controlled Trial (DecatSepsis)

Sepsis, especially septic shock, and its complications have been linked to the hyperadrenergic stress response. Does decatecholaminization with dexmedetomidine lower the in-hospital mortality in patients with septic shock? This open-label randomized controlled trial assessed the effects of a heart rate (HR)-calibrated dexmedetomidine infusion on in-hospital mortality in patients with septic shock and HR of > 90 beats/min, regardless of whether they are receiving mechanical ventilation. Dexmedetomidine was infused for 48h to maintain the HR at 60 to 90 beats/min. Mechanically ventilated patients received conventional sedation in both groups. Other outcomes were the norepinephrine equivalent dose, the need for additional vasopressor, Acute Physiology and Chronic Health Evaluation (APACHE) II score, persistent atrial fibrillation (AF), and C-reactive protein (CRP) level. In 90 patients of either sex, dexmedetomidine reduced the mean HR over the first 3days in the ICU by 11.2 beats/min (95%CI, -17 to -5 beats/min; P< .001). The in-hospital mortality risk ratio (RR) was 0.68 (95%CI, 0.43-1.07; P= .091). The dexmedetomidine group received a norepinephrine equivalent dose of 0.55 μm/kg/min (interquartile range [IQR], 0.37-0.82 μm/kg/min) vs0.61 μm/kg/min (IQR, 0.47-0.89 μm/kg/min; P= .121). Dexmedetomidine reduced the epinephrine infusion rescue (relative risk reduction, 0.6; 95%CI, 0.06-0.93; P= .025). The RR of persistent AF was 0.47 (95%CI, 0.21-0.99; P= .05). Dexmedetomidine reduced the median APACHE II score on the third day by -6 (95%CI, -10 to -2; P= .003) and the mean CRP concentration by -40mg/dL (95%CI, -78 to -3.4mg/dL; P= .033). The study was underpowered to detect a reduction in in-hospital mortality or norepinephrine equivalent dose in patients with septic shock with dexmedetomidine. However, dexmedetomidine may reduce epinephrine infusion rescue, persistent AF, the APACHE II score, and CRP. ClinicalTrials.gov; No.: NCT05283083; URL: www. gov.

The Impact of Weight-bearing Exercise, Non–Weight-bearing Exercise, and Cardiovascular Stress on Biochemical Markers of Cartilage Turnover in Patients With Mild to Moderate Knee Osteoarthritis: A Sequential, Cross-Over, Clinical Study

Objective To investigate how running, cycling, and sedentary cardiovascular stress impact biomarkers of cartilage turnover acutely in subjects with knee osteoarthritis (OA). Design This was a sequential, cross-over, clinical study. Forty subjects with primary knee OA underwent moderate-to-high-intensity cycling, running, and adrenaline infusion on separate days. Blood was sampled before, during, and at 6-time points after intervention. On a control day, similar samples were taken. Biomarkers of type II collagen degradation (C2M, T2CM, Coll2-1, Coll2-1NO2), formation (PRO-C2), and aggrecan degradation (ARGS) were measured. Results Mean age was 60.4 years, 40% were male, 45% had cumulated Kellgren-Lawrence (KL)-grade (Right + Left knee) of 2 to 3 and 55% had 4 to 6. Analyzing overall changes, area under the curve was significantly lower compared with resting values for ARGS and C2M after cycling and for ARGS after running. Considering individual time points, peak changes in biomarker levels showed reduction in C2M shortly following cycling (T20min = −12.3%, 95% confidence interval [CI]: −19.3% to −5.2%). PRO-C2 increased during cycling (T10min = 14.0%, 95% CI = 4.1% to 23.8%) and running (T20min = 16.5%, 95% CI = 4.3% to 28.6%). T2CM decreased after cycling (T50min = −19.9%, 95% CI = −29.2% to −10.6%), running (T50min = −22.8%, 95% CI = −32.1% to −13.5%), and infusion of adrenaline (peak, T50min = −9.8%, 95% CI = −20.0% to 0.4%). A latent increase was seen in Coll2-1 240 minutes after running (T260min = 21.7%, 95% CI = −1.6% to 45.1%). Conclusion Exercise had an impact on cartilage markers, but it did not suggest any detrimental effect on cartilage. Changes following adrenaline infusion suggest a sympathomimetic influence on the serological composition of biomarkers.

Epinephrine vs. phenylephrine infusion for prophylaxis against maternal hypotension after spinal anesthesia for cesarean delivery: a randomized controlled trial.

The hemodynamic effects of relatively low-dose epinephrine and phenylephrine infusions during cesarean delivery under spinal anesthesia were compared. This randomized controlled trial included full-term pregnant women who underwent elective cesarean delivery. After spinal anesthesia, participants received either epinephrine (0.03mcg/kg/min) or phenylephrine (0.4mcg/kg/min) infusion that continued until 5min after delivery. The primary outcome was a composite outcome of the occurrence of any of hypotension, hypertension, bradycardia, and/or tachycardia. Neonatal outcomes, including umbilical artery blood gas and Apgar scores, were assessed. In total, 98 patients in each group were analyzed, and the number of patients with the composite outcome was comparable between the epinephrine and phenylephrine groups (30/98 [31%] vs. 31/98 [32%], respectively; P = 0.877). However, the incidence of hypotension was likely lower in the epinephrine group than in the phenylephrine group (P = 0.066), and the number of hypotensive episodes per patient was lower in the epinephrine group than in the phenylephrine group. On the other hand, the incidence of tachycardia was higher in the epinephrine group than that in the phenylephrine group. The incidence of hypertension was comparable between the two groups and none of the participants developed bradycardia. Neonatal outcomes were comparable between the two groups. Epinephrine and phenylephrine infusion produced comparable maternal hemodynamics and neonatal outcomes. Epinephrine was associated with a higher incidence of maternal tachycardia and likely lower incidence of maternal hypotension than phenylephrine. IRB number: MD-245-2022. This study was registered on May 31, 2023 at clinicaltrials.gov registry, NCT05881915, URL: https://classic. gov/ct2/show/NCT05881915term=NCT05881915&draw=2&rank=1.

Associated factors of mortality and morbidity in emergency and elective abdominal surgery: a two-year prospective cohort study at lacor hospital, Uganda

BackgroundThe mortality rate associated with open abdominal surgery is a significant concern for patients and healthcare providers. This is particularly worrisome in Africa due to scarce workforce resources and poor early warning systems for detecting physiological deterioration in patients who develop complications.MethodsThis prospective cohort study aimed to follow patients who underwent emergency or elective abdominal surgery at Lacor Hospital in Uganda. The participants were patients who underwent abdominal surgery at the hospital between April 27th, 2019 and July 07th, 2021. Trained research staff collected data using standardized forms, which included demographic information (age, gender, telephone contact, and location), surgical indications, surgical procedures, preoperative health status, postoperative morbidity and mortality, and length of hospital stay.ResultsThe present study involved 124 patients, mostly male, with an average age of 35 years, who presented with abdominal pain and varying underlying comorbidities. Elective cases constituted 60.2% of the total. The common reasons for emergency and elective surgery were gastroduodenal perforation and cholelithiasis respectively. The complication rate was 17.7%, with surgical site infections being the most frequent. The mortality rate was 7.3%, and several factors such as preoperative hypotension, deranged renal function, postoperative use of vasopressors, and postoperative assisted ventilation were associated with it. Elective and emergency-operated patients showed no significant difference in survival (P-value = 0.41) or length of hospital stay (P-value = 0.17). However, there was a significant difference in morbidity (p < 0.001).ConclusionCholelithiasis and gastroduodenal perforation were key surgical indications, with factors like postoperative ventilation and adrenaline infusion linked to mortality. Emergency surgeries had higher complication rates, particularly surgical site infections, despite similar hospital stay and mortality rates compared to elective surgeries.

Propranolol Alleviates Cardiac Injury After Acute Catecholamine Infusion Through p38-MAPK Pathways.

Hypercatecholaminergic conditions are known to cause heart failure and cardiac fibrosis when severe. Although previous investigations have studied the effects of beta-blockade in experimental models of catecholaminergic states, the detailed benefits of beta-blockade in more realistic models of hyper-adrenergic states were less clear. In this study, we examined acute cardiac changes in rats with hyperacute catecholamine-induced heart failure with and without propranolol treatment. Male Sprague-Dawley rats (n = 12) underwent a 6-hour infusion of epinephrine and norepinephrine alone, with an additional propranolol bolus (1 mg/kg) at hour 1 (n = 6). Cardiac tissues were examined after 6 hours. Cardiac immunohistochemistry revealed significantly decreased expression of phosphorylated p-38 (left ventricle, P = 0.021; right ventricle, P = 0.021), with upregulation of reactive oxidative species and other profibrosis proteins, after catecholamine infusion alone. After 1 propranolol 1 mg/kg bolus, the levels of phosphorylated-p38 returned to levels comparable with sham (left ventricle, P = 0.021; right ventricle, P = 0.043), with additional findings including downregulation of the apoptotic pathway and profibrotic proteins. We conclude that catecholamine-induced heart failure exerts damage through the p-38 mitogen-activated protein kinase pathway and demonstrates profibrotic changes mediated by matrix metalloproteinase 9, alpha-smooth muscle actin, and fibroblast growth factor 23. Changes in these pathways attenuated acute catecholamine-induced heart failure after propranolol bolus 1 mg/kg. We conclude that propranolol bolus at 1 mg/kg is able to mediate the effects of catecholamine excess through the p-38 mitogen-activated protein kinase pathway, profibrosis, and extrinsic apoptosis pathway.

A retrospective, multi-agency ‘target trial emulation’ for the comparison of post-resuscitation epinephrine to norepinephrine

IntroductionEpinephrine and norepinephrine are the two most commonly used prehospital vasopressors in the United States. Prior studies have suggested that use of a post-ROSC epinephrine infusion may be associated with increased rearrest and mortality in comparison to use of norepinephrine. We used target trial emulation methodology to compare the rates of rearrest and mortality between the groups of OHCA patients receiving these vasopressors in the prehospital setting. MethodsAdult (18–80 years of age) non-traumatic OHCA patients in the 2018–2022 ESO Data Collaborative datasets with a documented post-ROSC norepinephrine or epinephrine infusion were included in this study. Logistic regression modeling was used to evaluate the association between vasopressor agent and outcome using two sets of covariables. The first set of covariables included standard Utstein factors, the dispatch to ROSC interval, the ROSC to vasopressor interval, and the follow-up interval. The second set added prehospital systolic blood pressure and SpO2 values. Kaplan-Meier time-to-event analysis was also conducted and the vasopressor groups were compared using a multivariable Cox regression model. ResultsOverall, 1,893 patients treated by 309 EMS agencies were eligible for analysis. 1,010 (53.4%) received an epinephrine infusion and 883 (46.7%) received a norepinephrine infusion as their initial vasopressor. Adjusted analyses did not discover an association between vasopressor agent and rearrest (aOR: 0.93 [0.72, 1.21]) or mortality (aOR: 1.00 [0.59, 1.69]). ConclusionsIn this multi-agency target trial emulation, the use of a post-resuscitation epinephrine infusion was not associated with increased odds of rearrest in comparison to the use of a norepinephrine infusion.

Metabolic effect of adrenaline infusion in people with type 1 diabetes and healthy individuals

Aims/hypothesisAs a result of early loss of the glucagon response, adrenaline is the primary counter-regulatory hormone in type 1 diabetes. Diminished adrenaline responses to hypoglycaemia due to counter-regulatory failure are common in type 1 diabetes, and are probably induced by exposure to recurrent hypoglycaemia, however, the metabolic effects of adrenaline have received less research attention, and also there is conflicting evidence regarding adrenaline sensitivity in type 1 diabetes. Thus, we aimed to investigate the metabolic response to adrenaline and explore whether it is modified by prior exposure to hypoglycaemia.MethodsEighteen participants with type 1 diabetes and nine healthy participants underwent a three-step ascending adrenaline infusion during a hyperinsulinaemic–euglycaemic clamp. Continuous glucose monitoring data obtained during the week before the study day were used to assess the extent of hypoglycaemia exposure.ResultsWhile glucose responses during the clamp were similar between people with type 1 diabetes and healthy participants, plasma concentrations of NEFAs and glycerol only increased in the group with type 1 diabetes (p<0.001). Metabolomics revealed an increase in the most common NEFAs (p<0.01). Other metabolic responses were generally similar between participants with type 1 diabetes and healthy participants. Exposure to hypoglycaemia was negatively associated with the NEFA response; however, this was not statistically significant.Conclusions/interpretationIn conclusion, individuals with type 1 diabetes respond with increased lipolysis to adrenaline compared with healthy participants by mobilising the abundant NEFAs in plasma, whereas other metabolic responses were similar. This may suggest that the metabolic sensitivity to adrenaline is altered in a pathway-specific manner in type 1 diabetes.Trial registrationClinicalTrials.gov NCT05095259Graphical

Safety of pre-hospital peripheral vasopressors: The SPOTLESS study (Safety of PrehOspiTaL pEripheral vaSopreSsors).

To assess the safety and effectiveness of peripheral vasoactive drugs initiated during pre-hospital care and retrieval missions, in Queensland, Australia. Three years of retrospective data was gathered from two sources. Medical notes were reviewed using a search for any patient having 'inotrope' recorded on an electronic medical record. Each case was reviewed to include only peripheral infusions of adrenaline or noradrenaline. Clinical Governance records were searched for adverse events related to vasoactive drugs, alerted for review to ensure complete capture. A total of 418 patients received peripheral infusions of adrenaline and noradrenaline over the 3-year period. No major complications were recorded either immediately or at Clinical Governance review. Minor complications were recorded in 4.7% of the cases, of which 3.5% occurred with peripheral vasoactives during the presence of the retrieval team. The frequency of use of peripheral vasoactives increased over the study period. In this retrospective data set there were no major complications of peripheral vasoactive drugs. Minor complications were similar to in-hospital use and related to vascular access and drug delivery.

Frequency of cardiotoxicity following intramuscular administration of epinephrine in emergency department patients with anaphylaxis.

Epinephrine can be a life-saving treatment for patients with anaphylaxis. Potential cardiovascular side effects of epinephrine may contribute to clinician hesitancy to use it. However, the frequency of cardiotoxicity resulting from epinephrine treatment for anaphylaxis is not well described. We sought to describe the frequency of cardiotoxicity following intramuscular (IM) administration of epinephrine in adult emergency department (ED) patients with anaphylaxis. We conducted a retrospective observational study at a single, quaternary care academic ED in Tennessee. We identified consecutive ED visits with the diagnosis of anaphylaxis from 2017 to 2021 who received at least one intramuscular (IM) dose of epinephrine in the ED. Analysis was primarily descriptive. The primary outcome was cardiotoxicity, the occurrence of any of the following after epinephrine administration: ischemic electrocardiogram changes, systolic blood pressure>200mmHg, or cardiac arrest ≤4h; elevated troponin ≤12h; or percutaneous coronary intervention or depressed ejection fraction ≤72h. Among 338 included patients, 16 (4.7%; 95%CI: 2.8-7.6%) experienced cardiotoxicity. Cardiotoxic events included eight (2.4%) ischemic electrocardiogram changes, six (1.8%) episodes of elevated troponin, five (1.5%) atrial arrhythmias, one (0.3%) ventricular arrythmia, and one (0.3%) depressed ejection fraction. Patients with cardiotoxicity were significantly older, had more comorbidities, and were more likely to have received multiple doses of epinephrine or an epinephrine infusion compared with a single IM dose of epinephrine. Among 338 consecutive adult ED patients who received IM epinephrine for anaphylaxis during a recent 4-year period, cardiotoxic side effects were observed in approximately 5% of patients.

Establishment of a swine experimental model of non-occlusive mesenteric ischemia: Combining induced hemorrhagic shock and vasopressor administration.

Non-occlusive mesenteric ischemia (NOMI) is associated with high mortality rates, but definitive treatments have not yet been established. Although experimental animal models are worthwhile, reproducible models that reflect the pathophysiology of NOMI have not been developed. We combined risk factors for NOMI, comprising hemorrhagic shock, systemic vasopressor infusion, and local vasopressor infusion from the superior mesenteric artery (SMA) in swine under maintained anesthesia. Experiment 1 involved full-intensity (40%) phlebotomy and systemic vasopressor (norepinephrine and epinephrine). Experiment 2 involved full-intensity (40%) phlebotomy, systemic norepinephrine, and local vasopressor infusion into the SMA. Experiment 3 involved moderate (27%) phlebotomy, systemic norepinephrine infusion, and local epinephrine infusion. We evaluated serum lactate levels, intestinal serosa color, computed tomography (CT) angiography, and pathological findings. After inducing hemorrhage, systemic vasopressor alone and in combination with local vasopressin or norepinephrine infusion did not induce ischemic color changes in the intestine. The combination of systemic norepinephrine and local epinephrine (0.5 μg/kg/min) after moderate (27% blood loss) hemorrhage induced gross color change, pathological destruction, and elevation of serum lactate. Patent flow in the SMA was confirmed on CT angiography. We established a swine NOMI model with systemic norepinephrine infusion and local epinephrine with moderate hemorrhagic shock.

Risk of arrhythmia in post-resuscitative shock after out-of-hospital cardiac arrest with epinephrine versus norepinephrine

ObjectiveTo determine the rates of clinically significant tachyarrhythmias and mortality in the management of post-resuscitative shock after return of spontaneous circulation (ROSC) in patients with out-of-hospital cardiac arrest (OHCA) who receive a continuous epinephrine versus norepinephrine infusion. DesignRetrospective cohort study. SettingA large multi-site health system with hospitals across the United States.Patients: Adult patients admitted for OHCA with post-resuscitative shock managed with either epinephrine or norepinephrine infusions within 6 h of ROSC. InterventionsNone. Measurements and main resultsBetween May 5th, 2018, to January 31st, 2022, there were 221 patients admitted for OHCA who received post-resuscitative epinephrine or norepinephrine infusions. There was no difference in the rate of tachyarrhythmias between epinephrine and norepinephrine infusion in univariate (47.1% vs 41.7%, OR 1.24, 95% CI 0.71–2.20) or multivariable analysis (OR 1.34, 95% CI 0.68–2.62). Patients treated with epinephrine were more likely to die during hospitalization than those treated with norepinephrine (90.0% vs 54.3%, OR 6.21, 95% CI 2.37–16.25, p < 0.001). Epinephrine treated patients were more likely to have re-arrest during hospital admission (55.7% vs 14.6%, OR 5.77, 95% CI 2.74–12.18, p < 0.001). ConclusionThere was no statistically significant difference in clinically significant cardiac tachyarrhythmias in post-OHCA patients treated with epinephrine versus norepinephrine infusions after ROSC. Re-arrest rates and in-hospital mortality were higher in patients who received epinephrine infusions in the first 6 h post-ROSC. Results of this study add to the literature suggesting norepinephrine may be the vasopressor of choice in post-OHCA patients with post-resuscitative shock after ROSC.

Hemoadsorption Therapy for Calcium Channel Blocker Overdose: A Case Report

BackgroundModern resin hemoadsorption/hemoperfusion for calcium channel blocker overdose is yet to be reported. The characteristics of calcium channel blockers make them unamenable to removal by hemodiafiltration or charcoal hemoperfusion; however, elimination, using styrene bead adsorption in an ex vivo model, has been demonstrated. Its clinical use is described. Case ReportA man in his 20s was admitted with shock into the Intensive Care Unit (ICU) after an overdose of amlodipine and risperidone. Resuscitation and supportive care were administered, but hypotension did not resolve despite the administration of intravenous fluids, infusions of calcium, adrenaline, and hyperinsulinemic-euglycemic therapy. Methylene blue was then administered to maintain the mean arterial pressures. However, the hemodynamic effect did not allow the weaning of the adrenaline. Drug clearance using hemoadsorption/hemoperfusion was attempted using a styrene resin filter (Jafron HA230; Jafron Biomedical Co., Ltd., Guangdong, China). During the two hemoperfusion sessions (6 h duration each, and 18 h apart) the patient had successfully weaned off all supportive measures, with lactate levels returning to normal and was later discharged home. At the end of each session, significant amlodipine concentrations were detected in blood aspirated from both filters, suggesting enhanced clearance. Why Should an Emergency Physician Be Aware of This?Our case illustrates a temporal relationship between resin hemoperfusion therapy, resolution of hemodynamic instability, and shock without proving causation. Significant amlodipine elimination was suggested by high concentrations found in blood from the filter. At the same time, shock resolution after initiation of hemoperfusion occurred in less than one elimination half-life of amlodipine.

Efficacy of Low Dose Intravenous Epinephrine Infusion in Improving Perioperative Outcomes in Patients Undergoing Transurethral Resection of Prostate: A Prospective Parallel Arm Double-Blind Randomized Control Trial

ObjectiveTo determine the efficacy of intraoperative low-dose intravenous epinephrine infusion in improving intraoperative bleeding and perioperative outcomes of TURP surgery. MethodsThis was a double-blinded, randomized control trial in which all patients undergoing bipolar TURP were included. Patients with uncontrolled hypertension, cardiac disease, and on anticoagulants were excluded. The study group received intravenous epinephrine, whereas the control group received normal saline at the same rate (0.05 μg/kg/min) throughout the procedure. Intraoperative blood loss was the primary outcome. The secondary outcomes were incidence of intraoperative hypotension (due to spinal anesthesia (SA)), resection time, indwelling catheter time, and length of hospitalization (LOH). ResultsThirty-six patients were included in each group. Demographic and clinical profiles were comparable with an overall median prostate size of 41 (34-52) gram in both groups. The primary objective, mean intraoperative blood loss in the study group was lower than the control group but statistically insignificant (67.91+/-18.7 ml vs 75.14+/-17.1 ml; p=0.086). Incidence of intraoperative hypotension was significantly lower in the study group (8.3% vs 33.3%; p= 0.01). Rest of the secondary outcomes, resection time (83 (64-111.5) min vs 86 (68-94.75) min; p=0.97), mean indwelling catheter time (p=0.94), postoperative complications (p=0.73), and LOH (p=0.87) were comparable. ConclusionsIn this first-of-its-kind trial, low-dose epinephrine infusion did not reduce intraoperative blood loss in patients undergoing TURP. However, it significantly reduced intraoperative hypotension, which complicates SA particularly in elderly population.