Epinephrine Infusion Research Articles

Abstract 13870: Ventricular Fibrillation Arrest in a 27-Year-Old Woman Due to Takotsubo Cardiomyopathy

Introduction: Sudden cardiac death in young patients may be due to coronary artery disease, primary electrical disease, cardiomyopathy, or congenital anomalies. We explore potential causes for sudden cardiac arrest in a young patient. Case Description: A 27-year-old woman was found unconscious. Initial rhythm showed ventricular fibrillation. Cardiopulmonary resuscitation was done for 5 minutes before return of spontaneous circulation. ECG showed ST elevations in aVL, V4, and V5. She was admitted for therapeutic temperature management. Troponin peaked at 1.86 ng/mL on the evening of arrival. Transthoracic echocardiography (TTE) demonstrated hypokinesis of the mid to distal septum, anterior wall, and apex (Figure 1). Repeat TTE 3 days later showed resolution of the wall motion abnormalities. She reported marijuana use and a domestic dispute with her significant other the night prior. Coronary CT angiography showed calcium score of 0 with normal coronary anatomy, no significant coronary artery stenosis, and incidental finding of bilateral pulmonary artery filling defects. Lower limb venous duplex was unremarkable. Therapeutic dose of enoxaparin was started. Cardiac MRI showed no myocardial infarction, scar, or infiltrative disease. An electrophysiology study revealed adequate QT shortening during epinephrine infusion and no inducible ventricular arrhythmias. Genetic testing was unremarkable. She was discharged with a wearable defibrillator before ultimately receiving a subcutaneous implantable cardioverter-defibrillator. Discussion: The presentation of transient regional wall motion abnormalities, with ST-segment elevations and negative ischemic workup, is highly suggestive of Takotsubo cardiomyopathy, mid-ventricular variant. Marijuana use is a risk factor, and the domestic dispute is a potential emotional trigger. This case highlights Takotsubo cardiomyopathy as a possible cause of sudden cardiac arrest in young patients.

Abstract 11687: Diagnosis and Management of High-Risk Pulmonary Embolism in a Term Neonate

Case Presentation: A 5 day old, term infant born to a 39-year-old G1P0 with a history of diet-controlled gestational diabetes mellitus presented with hypernatremic dehydration in the setting of poor feeding. On hospital day 2, the infant suffered a bradycardic cardiac arrest requiring 2 minutes of CPR prior to return of spontaneous circulation. An echocardiogram (Figure 1A) revealed moderately depressed right ventricular (RV) function, elevated RV pressure and a large mobile mass extending from the main pulmonary artery (PA) into the left PA with obstruction of flow. D-dimer was markedly elevated at 2740 ng/mL. A subsequent CT angiogram revealed acute pulmonary emboli in the distal left and right branch PAs (Figure 1B). Additional imaging was obtained and showed dural venous sinus, left portal vein and right cephalic vein thromboses. The infant was managed with a heparin infusion and supportive therapy for the RV dysfunction and pulmonary hypertension including mechanical ventilation, inhaled nitric oxide as well as epinephrine and milrinone infusions. Over the course of two weeks, the infant improved clinically with normalization of RV function. Discussion: Neonatal pulmonary arterial thrombosis is an exceedingly rare phenomenon. The majority of cases described in the literature are associated with either an inherited thrombophilia or with underlying congenital heart disease, which were not found to be present in this case. However, this patient presented with severe dehydration and a history of maternal diabetes, both of which are risk factors for neonatal thrombosis. Fortunately, this patient responded to treatment with anticoagulation alone and did not require more invasive therapies, such as surgical thrombectomy or systemic and catheter-directed thrombolysis. Although rare, neonatal pulmonary arterial thrombosis can occur and delays in recognition and treatment may lead to significant RV dysfunction, morbidity, and even death.

Abstract 15332: Post-Resuscitation Epinephrine Infusion Restores Blood Pressure but Not Blood Flow in a Rat Model of Severe Pediatric Cardiac Arrest

Introduction: In children resuscitated from cardiac arrest (CA), post-arrest hypotension occurs often and worsens outcomes. Continuous infusion of epinephrine (Epi) is the 1st-line treatment for post-arrest hypotension but may worsen organ perfusion due to vasoconstriction. Hypothesis: Epi infusion after resuscitation from pediatric asphyxial CA restores blood pressure but not organ perfusion. Methods: Immature rats (PND18-22, n=34) underwent 11.5 minutes of asphyxial CA followed by resuscitation. Rats with hypotension (mean arterial pressure (MAP)<80% baseline) after resuscitation received infusions of either 0.9% NaCl (NS) or Epinephrine (Epi). MAP, carotid and femoral arterial blood flows (Fc, Ff) and renal oxygen tension (PrO2) were recorded. Results: One hour after resuscitation, MAP, Fc and Ff were 61.73 ± 2.68; 42.58 ± 3.84; and 19.53 ± 7.00 % of baseline, respectively. Epi infusion increased MAP in a dose-dependent manner, reaching 95.13 ± 7.93 % of baseline at 0.5 μg/kg/min. In contrast, Epi infusion up to 0.5 μg/kg/min increased Fc only to 49.55 ± 6.49 and Ff to 53.28 ± 7.13 % of baseline. NS infusion at equivalent volume had a more salutary effect than Epi on improving blood flow (Fc 64.62 ± 6.64 and Ff 60.25 ± 7.60 % of baseline). PrO2 reached 100% of baseline with Epi infusion and inspired O2 fraction (FiO2) = 1. However, at FiO2 = 0.21, Epi failed to restore PrO2 which reached 42% of baseline. Interestingly, a single 10 cc/kg NS bolus increased PrO2 to 100% of baseline at all FiO2 tested. Conclusions: In this rat model of severe pediatric asphyxial CA and resuscitation, post-resuscitation Epi infusion failed to restore carotid and femoral arterial blood flow despite normalizing blood pressure. Furthermore, Epi infusion restored neither renal perfusion nor oxygenation. In contrast, infusion of NS at comparable volumes was more effective than Epi at normalizing carotid and femoral blood flows as well as renal oxygenation. If validated in a large animal model, these results may indicate that Epi infusion after CA resuscitation contributes to organ injury and morbidity in children.

ABRAXANE DESENSITIZATION

<h3>Introduction</h3> Adverse and hypersensitivity reactions to Taxol chemotherapy are not uncommon. The Cremophor solvent used in Taxol formulations has been associated with adverse infusion and delayed reactions. A biosimilar agent, Abraxane, which uses an albumin solvent, is often better tolerated. We present a case of severe hypersensitivity to Taxol and a unique protocol for Abraxane desensitization. <h3>Case Description</h3> A 38-year-old female with endometrial cancer presented with rash and lip swelling seven days after her first Carboplatin and Paclitaxel (Taxol) doses. She tolerated a Carboplatin challenge ruling out Carboplatin as the culprit. While undergoing a Paclitaxel challenge, she experience an anaphylactic reaction requiring intubation and epinephrine infusion. Given the severity of her reaction, there was concern that patient had reacted to Paclitaxel and not the solvent alone. Thus, her treatment plan was switched to Abraxane with plan to desensitize patient first. Desensitization to Abraxane was complicated by lack of medication stability once mixed and risk of medication dissociation with dilution. A unique 1 bag desensitization protocol was created. During Abraxane desensitization, patient had a hypersensitivity reaction which was treated with Benadryl and Methylprednisolone. Patient tolerated the remainder of the Abraxane desensitization. <h3>Discussion</h3> We report a challenging case of a patient with both immediate and delayed hypersensitivity reactions to Paclitaxel, who was able to undergo successful desensitization to Abraxane through a unique 1 bag protocol despite limitations of medication stability and dilution capabilities. Furthermore, patient's IgE-mediated reactions to both Paclitaxel and Abraxane further demonstrate that she is indeed allergic to the active ingredient and not the solvent.

Temporal Changes in Epinephrine Dosing in Out-of-Hospital Cardiac Arrest: A Review of EMS Protocols across the United States.

Administration of epinephrine has been associated with worse neurological outcomes for survivors of out-of-hospital cardiac arrest. The publication of the 2018 PARAMEDIC-2 trial, a randomized and double-blind study of epinephrine in out-of-hospital cardiac arrest, provides the strongest evidence to date that epinephrine increases return of spontaneous circulation (ROSC) but not neurologically intact survival. This study aims to determine if Emergency Medical Services (EMS) cardiac arrest protocols have changed since the publication of PARAMEDIC-2. States in the US utilizing mandatory or model state-wide EMS protocols, including Washington DC, were included in this study. The nontraumatic cardiac arrest protocol as of January 1, 2018 was compared to the protocol in effect on January 1, 2021 to determine if there was a change in the administration of epinephrine. Protocols were downloaded from the relevant state EMS website. If a protocol could not be obtained, the state medical director was contacted. A 2021 state-wide protocol was found for 32/51 (62.7%) states. Data from 2018 were available for 21/51 (41.2%) states. Of the 11 states without data from 2018, all follow Advanced Cardiac Life Support (ACLS) guidelines in the 2021 protocol. Five (15.6%) of the states with a state-wide protocol made a change in the cardiac arrest protocols. Maximum cumulative epinephrine dose was limited to 4mg in Maryland and 3mg in Vermont. Rhode Island changed epinephrine in shockable rhythms to be administered after three cycles of cardiopulmonary resuscitation (CPR) and an anti-arrhythmic. Rhode Island also added an epinephrine infusion as an option. No states removed epinephrine administration from their cardiac arrest protocol. Simple statistical analysis was performed with Microsoft Excel. Several states have adjusted cardiac arrest protocols since 2018. The most frequent change was limiting the maximum cumulative dosage of epinephrine. One state changed timing of epinephrine dosing depending on the rhythm and also provided an option of an epinephrine infusion in place of bolus dosing. While the sample size is small, these changes may reflect the future direction of prehospital cardiac arrest protocols. Significant limitations apply, including the exclusion of local and regional protocols which are more capable of quickly adjusting to new research. Additionally, this study is only focused on EMS in the United States.

Fluid Resuscitation and Inotropic Support in Patients With Septic Shock Treated in Pediatric Emergency Department: An Open-Label Trial.

IntroductionFluid resuscitation and inotropic support are essential interventions to improve cardiovascular function in patients with septic shock. However, the optimal volume of fluids and the timing of inotropic support to achieve the resolution of shock are controversial. They may depend on the availability of critical care support services. AimsTo compare early versus the delayed start of epinephrine administration after fluids bolus in children with septic shock. Methods We conducted an open-label randomized trial in which patients under 18 years of age diagnosed with septic shock and arterial hypotension were treated in two Pediatric Emergency Departments in Paraguay (Hospital de Clinicas of Universidad Nacional de Asunción and Instituto Privado del Niño) between 2015 and 2020. Septic shock was defined according to the American College of Critical Care Medicine (ACCM) guidelines. All patients received antibiotics and 40 ml/kg of fluids (two boluses of 20ml/kg if there were no signs of fluid overload) during the first hour. They were then divided into two groups: Group 1 received epinephrine infusion and maintenance fluids. Group 2 received an additional 20 ml/kg of fluids and then was started on epinephrine infusion. ResultsOf 229 patients screened, 63 patients were included in the study. The mean age was 2.8±3.5 years. A total of 52% were female. Group 1 comprised 33 patients, and group 2 comprised a total of 30. Significant differences were found between group 1 and group 2 in the following: mortality (10% vs. 33%, p: 0.026, RR: 3.1, CI: 95%: 1-10), need for mechanical ventilation (10% vs. 41%, p: 0.006, RR: 4, CI: 95%: 1.3-12), and altered vascular hypoperfusion after one hour of interventions (7% vs. 59%, p<0,001, RR: 8.2, CI: 95%: 2-32).ConclusionsEarly administration of epinephrine infusion after initial fluid therapy was associated with better clinical outcomes than delayed administration.

Paradoxical worsening of bradycardia following atropine administration.

Bradyarrhythmias are a common entity in both emergency and out-of-hospital (OOH) medicine. In unstable bradycardic patients, paramedics will often initiate life-saving therapies in the OOH setting. Clinical guidelines for bradyarrhythmias are largely consistent across the globe, with intravenous (IV) atropine recommended as a first-line therapy, escalating to IV adrenaline or isoprenaline and transcutaneous pacing where atropine is unsuccessful. In this case report, we describe a case in the OOH setting of ventricular standstill following the administration of atropine to a patient with bradycardia and 2:1 heart block. The patient was a 77-year-old female presenting with a symptomatic 2:1 heart block. Following a single dose of 600 micrograms IV atropine, the patient deteriorated into ventricular standstill with a loss of consciousness and decorticate posturing. The patient was successfully managed with an IV infusion of adrenaline and subsequently received an implanted pacemaker in hospital. The paradoxical worsening of this patient's bradycardia following atropine administration may have been related to the location of the heart block. It has been shown that patients with atrioventricular blocks at the level of the His-Purkinje fibres (infranodal) are at an increased risk of adverse events following atropine administration, while those at the nodal level or secondary to increased vagal tone are more likely to respond favourably. Paramedics should be prepared to manage unexpected adverse events secondary to atropine administration in patients with heart block.

Effect of adrenaline on serum mid-regional pro-atrial natriuretic peptide and central blood volume.

New Findings What is the central question in this study? Atrial natriuretic peptide (ANP) is secreted in response to atrial wall distension and thus allows for evaluation, albeit indirect, of the central blood volume. Adrenaline has chronotropic and inotropic effects. We evaluated whether the chronotropic and inotropic effects of adrenaline were reflected in mid‐regional proANP. What is the main finding and its importance? Central blood volume remained stable with infusion of adrenaline and yet mid‐regional proANP increased. Thus, the chronotropic and inotropic state of the heart or adrenaline directly induces release of ANP variants from the myocytes. Atrial natriuretic peptide (ANP) has vasodilatory, natriuretic and diuretic properties. It is secreted in response to atrial wall distension and thereby provides an indirect evaluation of central blood volume (CBV). Adrenaline has chronotropic and inotropic effects that increase cardiac output. In the present study, we evaluated whether these effects were influenced by an increase in CBV and reflected in mid‐regional proANP (MR‐proANP) concentrations in the circulation, a stable proxy marker of bioactive ANP. Changes in CBV were evaluated by thoracic electrical admittance and haemodynamic variables monitored by pulse‐contour analysis during two intervals with graded infusion of adrenaline. Adrenaline infusion increased heart rate (by 33 ± 18%) and stroke volume (by 6 ± 13%), hence cardiac output (by 42 ± 23%; all P < 0.05). The increase in cardiac output did not result from an increase in CBV, because thoracic electrical admittance remained stable (−3 ± 17%; P = 0.230). Serum MR‐proANP concentrations were increased (by 26 ± 25%; P < 0.001) by adrenaline infusion and remained elevated 60 min postinfusion. We conclude that MR‐proANP in the circulation is affected not only by CBV, but also by increased chronotropy/inotropy of the heart, or that adrenaline directly induces release of ANP variants from the myocytes.

Cardiac Arrest Caused by Anaphylaxis Refractory to Prompt Management

BackgroundAnaphylaxis is a potentially life-threatening condition that occurs in the emergency department (ED). Although anaphylaxis is rapidly recognized and treated in the hospital compared with that in the community, in some cases, it does not respond to proper management. ObjectiveThe aim of this study is to describe our experience of cases of refractory anaphylaxis leading to cardiac arrest in hospital, to review their characteristics compared with those seen in the community, and to discuss the best management practices for anaphylaxis-induced cardiac arrest with a literature review. MethodsWe reviewed the medical records of patients referred to the ED with possible in-hospital anaphylaxis between January 2017 and May 2021. According to the anaphylaxis protocol, epinephrine, corticosteroid, and antihistamine were administered immediately on-site at our institution before the study period. Refractory anaphylaxis was defined as the development of anaphylaxis-induced cardiac arrest even after following the anaphylaxis protocol. ResultsA total of 246 cases were evaluated for possible anaphylaxis, with 236 cases meeting the criteria for a diagnosis of anaphylaxis. Among them, 178 patients showed the signs and symptoms of shock, and cardiac arrest occurred in 6 patients (2.5%). Of the six patients, three had a return of spontaneous circulation before admission to the ED, while two died due to refractory cardiac arrest despite resuscitation in the ED. Following post-cardiac arrest care, including temperature management, one patient who received extracorporeal cardiopulmonary resuscitation survived neurologically intact. ConclusionWe present our case series to highlight the risk of developing refractory anaphylaxis with subsequent in-hospital cardiac arrest. Patients may progress to cardiac arrest within minutes despite prompt recognition and management. If patients present with potentially fatal symptoms, a more aggressive approach, including intravenous adrenaline infusion, should be taken.

Medical evacuation of non-transportable newborns after re-evaluation

BACKGROUND: Early admission or birth in a high-level neonatal care facility is associated with lower morbidity in preterm infants. Assessment of transportability remains a problem of the pre-transport evaluation. The literature data lacks the possibility of subsequent evacuation of patients recognized as non-transportable at the first examination.&#x0D; AIM: This study compares intensive care during the first and second examinations of patients recognized as non-transportable and evacuated after re-departure.&#x0D; MATERIALS AND METHODS: The cohort study included data from patients recognized as non-transportable at the first examination and evacuated after the second examination (18 patients). Comparison of intensive care, assessments by scales, correction of intensive care by the transport team during the first and repeated examinations of the patient was performed. Descriptive statistics methods, Wilcoxons test, and McNemars test were applied.&#x0D; RESULTS: Patients evacuated on the second attempt had a birth weight of less than 1500 grams. The median birth weight was 1125 [7403240] grams. The patients were reliably more often on traditional mechanical ventilation and less on high-frequency ventilation at the second examination. The infusion of adrenaline and prostaglandins was more often performed. The average number of corrective actions per patient at the first examination was 1.33 (SD 0.77), at the second examination 0.5 (SD 0.62), p = 0.003. During the first attempt at evacuation, patients significantly more often required the administration or correction of the catecholamine dose, tracheal reintubation, and blood transfusion.&#x0D; CONCLUSION: The data obtained indicate the inadequacy of the therapy performed before the arrival of the transport team contributes to the decision on the patients non-transportability.

An Estimate of Plasma Volume Changes Following Moderate-High Intensity Running and Cycling Exercise and Adrenaline Infusion.

Introduction: Plasma volume (PV) changes in response to physical activity, possibly as a consequence of adrenergic activation. We estimated changes in PV in response to common exercise modalities; cycling and running as well as adrenaline infusion and control at rest. Methods: On separate days, forty circulatory healthy subjects [aged 60 years (range: 42–75)] with knee osteoarthritis underwent moderate-high intensity cycling, running, and intravenous adrenaline infusion to mimic the circulatory response to exercise. Blood samples were obtained from peripheral veins taken at several pre-defined time points before, during, and after the interventions. PV changes were estimated using venous hemoglobin and the derived hematocrit. The temporal associations between PV and selected biomarkers were explored. Results: Changes in PV were observed during all four interventions, and the response to cycling and running was similar. Compared to rest, PV decreased by -14.3% (95% CI: -10.0 to -18.7) after cycling, -13.9% (95% CI: -10.9 to -17.0) after running, and -7.8% (95% CI: -4.2 to -11.5) after adrenaline infusion. Conclusion: PV decreased in response to moderate-high intensity running and cycling. Adrenaline infusion mimicked the PV change observed during exercise, suggesting a separate influence of autonomic control on blood volume homeostasis. In perspective, a temporal association between PV and biomarker dynamics suggests that consideration of PV changes could be relevant when reporting plasma/serum constituents measured during exercise, but more research is needed to confirm this.

A retrospective study of antivenom-associated adverse reaction and anaphylaxis at Ngwelezana Hospital, South Africa

BackgroundSnakebite victims are commonly seen in KwaZulu-Natal Hospitals, with only a minority of patients requiring antivenom. This study reviewed antivenom-associated adverse events at our institution, after administration of the South African Vaccine Producers (SAVP) polyvalent antivenom. MethodsA retrospective review, over 52 months (January 2016–April 2020), of patients who received antivenom. Demographics, clinical details and clinical course following antivenom administration were analysed. ResultsEmergency department doctors treated 758 snakebites; 156 patients were admitted of which 51 (33%) received antivenom. Indications for antivenom included: neurotoxicity (24%), haemotoxicity (18%) and significant cytotoxicity (58%). Antivenom-associated adverse events occurred in 61% of patients; with 47% developing anaphylaxis requiring adrenaline infusion. There was a higher incidence of anaphylaxis in children (57%) than in adults (40%), p = 0.55. There was no association between antivenom dose and anaphylaxis. No benefit was noted with adrenaline premedication (p = 0.64), nor with the addition of antihistamine or steroid pre-medicants to adrenaline (p = 0.61). Multivariable logistic regression identified age as a predictor for anaphylaxis, but not dose or duration of antivenom and not any particular form of premedication. Intubation was required in 29% of patients developing anaphylaxis. There were no deaths and all patients made full recovery. ConclusionAlmost half of the patients at Ngwelezana hospital in Kwazulu-Natal receiving the SAVP polyvalent antivenom developed anaphylaxis requiring adrenaline infusion, with children at higher risk. The administration of this antivenom must only be given for valid indications, in a high-care environment by medical personnel ready to manage anaphylactic shock. The addition of antihistamine and corticosteroids to adrenaline for premedication has no added benefit.

Immediate extubation following pediatric liver transplantation.

Immediate extubation (IE) following pediatric liver transplantation is being increasingly performed. The aim of this study was to characterize the rate of IE at our institution and identify recipient factors predictive of IE. All pediatric liver transplants performed at our institution between January 1, 2015 and December 31, 2020 were reviewed. Retransplants and multi-organ transplants were excluded. IE was defined as extubation in the operating room following transplant. Backward stepwise logistic regression at a p-value threshold of .05 was performed to identify variables associated with IE. IE was achieved in 58 (72%) of the 81 pediatric liver transplants. The IE cohort had significantly shorter ICU length of stay and overall hospital length of stay, though IE was not an independent predictor of posttransplant length of stay. Age <2 years, preoperative mechanical ventilation, and total intraoperative epinephrine and dopamine infusion requirements were significant, independent risk factors against IE. This multivariable model was highly predictive of IE (area under the curve=0.89). We describe the highest rate of IE postpediatric liver transplantation that has been reported to date and identified significant risk factors against successful IE.

Utility of Provocative Testing in the Diagnosis and Genotyping of Congenital Long QT Syndrome: A Systematic Review and Meta-Analysis.

Background Diagnosis is particularly challenging in concealed or asymptomatic long QT syndrome (LQTS). Provocative testing, unmasking the characterization of LQTS, is a promising alternative method for the diagnosis of LQTS, but without uniform standards. Methods and Results A comprehensive search was conducted in PubMed, Embase, and the Cochrane Library through October 14, 2021. The fixed effects model was used to assess the effect of the provocative testing on QTc interval. A total of 22 studies with 1137 patients with LQTS were included. At baseline, QTc interval was 40ms longer in patients with LQTS than in controls (mean difference [MD], 40.54 [95% CI, 37.43-43.65]; P<0.001). Compared with the control group, patients with LQTS had 28ms longer ΔQTc upon standing (MD, 28.82 [95% CI, 23.05-34.58]; P<0.001), nearly 30ms longer both at peak exercise (MD, 27.31 [95% CI, 21.51-33.11]; P<0.001) and recovery 4 to 5minutes (MD, 29.85 [95% CI, 24.36-35.35]; P<0.001). With epinephrine infusion, QTc interval was prolonged both in controls and patients with QTS, most obviously in LQT1 (MD, 68.26 [95% CI, 58.91-77.60]; P<0.001) and LQT2 (MD, 60.17 [95% CI, 50.18-70.16]; P<0.001). Subgroup analysis showed QTc interval response to abrupt stand testing and exercise testing varied between LQT1, LQT2, and LQT3, named Type Ⅰ, Type Ⅱ, and Type Ⅲ. Conclusions QTc trend Type Ⅰ and Type Ⅲ during abrupt stand testing and exercise testing can be used to propose a prospective evaluation of LQT1 and LQT3, respectively. Type Ⅱ QTc trend combined epinephrine infusion testing could distinguish LQT2 from control. A preliminary diagnostic workflow was proposed but deserves further evaluation.

Transportability of newborns at the stage of pre-transport evaluation

with the necessary resources and technology to improve the level and quality of care remains one of the most important tasks of emergency neonatology. Deterioration on the road may be due to suboptimal stabilization, the severity of the patient's condition, and the transportation procedure itself. Assessment of transportability is one of the most important tasks in the pre-transport preparation phase. Materials and Methods. The cohort study included data from 604 resuscitation team visits. According to the tactical decision, the subgroups of the transportable (n = 497) and non-transportable (n = 46) patients were singled out. The anamnesis data, scores according to the KSHONN, NTISS, TRIPS threat scales, the volume of intensive care, pre-transport preparation, and the outcome of the hospital stage were analyzed. Results. Non-transportable patients had significantly higher scores on the examined threatometric scales. The need for high-frequency artificial lung ventilation was associated with patient nontransportability with a risk ratio of 10.1 [6.72 to 15.18], and dopamine and adrenaline infusion increased the likelihood of nontransportability with risk ratios of 5.85 [3.44 to 9.95] and 11.38 [8.09 to 16.01], respectively. The need for correction of intensive care is associated with nontransportability with a risk ratio of 3.44 [2.29 to 5.17]. The group of nontransportable patients was characterized by significantly higher mortality, 7-day mortality, frequency of late neonatal sepsis, and longer duration of ventilatory ventilation and intensive care. Discussion. The group of patients considered untransportable at the stage of pre-transport preparation is characterized by high morbidity, the need for intensive care, and the need to correct therapy, which is regarded by the transport team as an additional risk. Conclusion. Non-transportable patients are characterized by a significantly higher need for intensive care and amount of pre-transport preparation, high morbidity and mortality

Manganese Porphyrin Promotes Post Cardiac Arrest Recovery in Mice and Rats.

Simple SummaryAlthough heart failure is a long-term chronic disease, it can also lead to arrhythmia, triggering cardiac arrest, and eventually death. Our study is a randomized and blinded preclinical assessment of the efficacy of the Mn porphyrin compound, MnTnBuOE-2-PyP5+ (BMX-001), commonly known as a superoxide dismutase mimic, in both mouse and rat models of cardiac arrest and resuscitation. Our study indicates that MnTnBuOE-2-PyP5+ improves survival, neurologic function recovery, and behavioral performance in animals suffering from cardiac arrest. The results support the development of Mn Porphyrin-based therapeutics for the treatment of heart failure and cardiac arrest.Introduction Cardiac arrest (CA) and resuscitation induces global cerebral ischemia and reperfusion, causing neurologic deficits or death. Manganese porphyrins, superoxide dismutase mimics, are reportedly able to effectively reduce ischemic injury in brain, kidney, and other tissues. This study evaluates the efficacy of a third generation lipophilic Mn porphyrin, MnTnBuOE-2-PyP5+, Mn(III) ortho meso-tetrakis (N-n-butoxyethylpyridinium-2-yl)porphyrin (MnBuOE, BMX-001), in both mouse and rat models of CA. Methods Forty-eight animals were subjected to 8 min of CA and resuscitated subsequently by chest compression and epinephrine infusion. Vehicle or MnBuOE was given immediately after resuscitation followed by daily subcutaneous injections. Body weight, spontaneous activity, neurologic deficits, rotarod performance, and neuronal death were assessed. Kidney tubular injury was assessed in CA mice. Data were collected by the investigators who were blinded to the treatment groups. Results Vehicle mice had a mortality of 20%, which was reduced by 50% by MnBuOE. All CA mice had body weight loss, spontaneous activity decline, neurologic deficits, and decreased rotarod performance that were significantly improved at three days post MnBuOE daily treatment. MnBuOE treatment reduced cortical neuronal death and kidney tubular injury in mice (p < 0.05) but not hippocampus neuronal death (23% MnBuOE vs. 34% vehicle group, p = 0.49). In rats, they had a better body-weight recovery and increased rotarod latency after MnBuOE treatment when compared to vehicle group (p < 0.01 vs. vehicle). MnBuOE-treated rats had a low percentage of hippocampus neuronal death (39% MnBuOE vs. 49% vehicle group, p = 0.21) and less tubular injury (p < 0.05) relative to vehicle group. Conclusions We demonstrated the ability of MnBuOE to improve post-CA survival, as well as functional outcomes in both mice and rats, which jointly account for the improvement not only of brain function but also of the overall wellbeing of the animals. While MnBuOE bears therapeutic potential for treating CA patients, the females and the animals with comorbidities must be further evaluated before advancing toward clinical trials.

Continuous cardiac output measured with a Swan‐Ganz catheter reacts too slowly in animal experiments with sudden circulatory failure

BackgroundIn many animal experiments, it is vital to detect sudden changes in cardiac output (CO). This porcine study compared CO that was measured with a Swan‐Ganz pulmonary catheter with the gold standard (which was a transit‐time flow probe around the pulmonary artery) during interventions that caused hemodynamic instability.MethodsIn one series, 7 pigs were exposed to sudden changes in CO. In another series, 9 pigs experienced more prolonged changes in CO. All the pigs had a Swan‐Ganz catheter placed into the pulmonary artery and a flow probe around the pulmonary artery. Adrenaline infusion and controlled hemorrhage were used to increase and decrease CO, respectively. The measurements of CO before and after each intervention were compared for correlation, agreement, and the time delay that it took each method to detect at least a 30% change in CO. A Bland–Altman test was used to identify correlations and agreements between the methods.ResultsIn the first series, there was a delay of 5–7 min for the Swan Ganz catheter to register a 30% change in cardiac output, compared with the flow probe. However, during prolonged changes in CO in the second series, there was a good correlation between the 2 methods. Mixed venous oxygen saturation reacted faster to changes than did CO; both were measured via the Swan‐Ganz catheter.ConclusionsIn many animal studies, the use of Swan‐Ganz catheters is suitable; however, in experiments with sudden hemodynamic instability, the flow probe is the most advantageous method for measuring CO.

A physiology-based trigger score to guide perioperative transfusion of allogeneic red blood cells: A multicentre randomised controlled trial.

Restrictive blood transfusion is recommended by major guidelines for perioperative management, but requires objective assessment at 7-10g/dl haemoglobin (Hb). A scoring system that considers the physiological needs of the heart may simply the practice and reduce transfusion. Patients (14-65 years of age) undergoing non-cardiac surgery were randomised at a 1:1 ratio to a control group versus a Perioperative Transfusion Trigger Score (POTTS) group. POTTS (maximum of 10) was calculated as 6 plus the following: adrenaline infusion rate (0 for no infusion, 1 for ≤0.05 μg·kg-1 ·min-1 , and 2 for higher rate), FiO2 to keep SpO2 at ≥95% (0 for ≤35%, 1 for 36%-50%, and 2 for higher), core temperature (0 for <38°C, 1 for 38-40°C, and 2 for higher), and angina history (0 for no, 1 for exertional, and 2 for resting). Transfusion is indicated when actual Hb is lower than the calculated POTTS in individual patients. Transfusion in the control group was based on the 2012 American Association for Blood Banks (AABB) guideline. The primary outcome was the proportion of the patients requiring transfusion of allogeneic red blood cells (RBCs) during the perioperative period (until discharge from hospital), as assessed in the intention-to-treat (ITT) population (all randomised subjects). A total of 864 patients (mean age 44.4 years, 244 men and 620 women) were enrolled from December 2017 to January 2021 (433 in the control and 431 in the POTTS group). Baseline Hb was 9.2 ± 1.8 and 9.2 ± 1.7g/dl in the control and POTTS groups, respectively. In the ITT analysis, the proportion of the patients receiving allogeneic RBCs was 43.9% (190/433) in the control group versus 36.9% (159/431) in the POTTS group (p=0.036). Lower rate of allogeneic RBCs transfusion in the POTTS group was also evident in the per-protocol analysis (42.8% vs. 35.5%, p=0.030). Transfusion volume was 4.0 (2.0, 6.0) and 3.5 (2.0, 5.5) units (200 ml/unit) in the control and POTTS groups, respectively (p=0.25). The rate of severe postoperative complications (Clavien-Dindo grade IIIa and higher) was 3.9% in the control group versus 1.2% in the POTTS group (p=0.010). Transfusion of allogeneic RBCs based on the POTTS was safe and reduced the transfusion requirement in patients undergoing non-cardiac surgery.

Variable‐rate infusion of adrenaline to manage hypotension in an anaesthetised goat

AbstractTreatment of hypotension in domestic ruminants is more challenging than in other species, due to strict drug legislation and a limited number of licensed drugs in food‐producing animals. The use of adrenaline as a variable‐rate infusion to improve haemodynamics is a viable treatment option when other interventions fail. Further studies are needed to establish appropriate infusion rates and potential side effects in goats.

Low-Dose Propranolol Prevents Functional Decline in Catecholamine-Induced Acute Heart Failure in Rats.

Severe hyper-catecholaminergic states likely cause heart failure and cardiac fibrosis. While previous studies demonstrated the effects of beta-blockade in experimental models of single-catecholamine excess states, the detailed benefits of beta-blockade in more realistic models of hyper-adrenergic states are less clearly understood. In this study, we examined different therapeutic dosages and the effects of propranolol in rats with hyper-acute catecholamine-induced heart failure, and subsequent cardiopulmonary changes. Rats (n = 41) underwent a 6 h infusion of epinephrine and norepinephrine alone, with additional low-dose (1 mg/kg) or high-dose propranolol (10 mg/kg) at hour 1. Cardiac and pulmonary tissues were examined after 6 h. Catecholamine-only groups had the lowest survival rate. Higher doses of propranolol (15 mg/kg) caused similarly low survival rates and were not further analyzed. All low-dose propranolol rats survived, with a modest survival improvement in the high-dose propranolol groups. Left ventricular (LV) systolic pressure and LV end-diastolic pressure improved maximally with low-dose propranolol. Cardiac immunohistochemistry revealed an LV upregulation of FGF-23 in the catecholamine groups, and this improved in low-dose propranolol groups. These results suggest catecholamine-induced heart failure initiates early pre-fibrotic pathways through FGF-23 upregulation. Low-dose propranolol exerted cardio-preventative effects through FGF-23 downregulation and hemodynamic-parameter improvement in our model of hyper-acute catecholamine-induced heart failure.