A Comparative Study to Evaluate the Effect of Norepinephrine and Phenylephrine in the Treatment of Post Spinal Hypotension for Caesarean Section

Background: Maternal hypotension due to spinal anaesthesia in caesarean section is commonly seen. Alongwith fluid loading, phenylephrine is used to manage the hypotension. However, this drug is associated with cardiovascular side effects. Methods: This is a prospective double blinded study which was conducted on 100 term parturients scheduled from elective caesarean section under spinal anaesthesia, randomly assigned into two groups. After spinal anaesthesia patients of group N and P were treated with norepinephrine (5mcg) and phenylephrine (50mcg) respectively as an IV bolus for hypotension. Blood pressure, heart rate, number of bolus doses given, and neonatal APGAR score was noted. Results: Patients of both groups were comparable with respect to haemodynamic parameters (HR, SBP, DBP, AND MAP). Incidence of bradycardia was higher in group P (22%, n=11) compared to group N (14%, n=7). Neonatal APGAR scores at different time intervals were similar in both groups. Conclusion: Intermittent boluses of norepinephrine were effective in the treatment of spinal anaesthesia induced hypotension during caesarean section and can be considered as an alternative to phenylephrine.

Robotics and the Airway Management

Background: Maternal hypotension due to spinal anaesthesia in caesarean section is commonly seen. Alongwith fluid loading, phenylephrine is used to manage the hypotension. However, this drug is associated with cardiovascular side effects. Methods: This is a prospective double blinded study which was conducted on 100 term parturients scheduled from elective caesarean section under spinal anaesthesia, randomly assigned into two groups. After spinal anaesthesia patients of group N and P were treated with norepinephrine (5mcg) and phenylephrine (50mcg) respectively as an IV bolus for hypotension. Blood pressure, heart rate, number of bolus doses given, and neonatal APGAR score was noted. Results: Patients of both groups were comparable with respect to haemodynamic parameters (HR, SBP, DBP, AND MAP). Incidence of bradycardia was higher in group P (22%, n=11) compared to group N (14%, n=7). Neonatal APGAR scores at different time intervals were similar in both groups. Conclusion: Intermittent boluses of norepinephrine were effective in the treatment of spinal anaesthesia induced hypotension during caesarean section and can be considered as an alternative to phenylephrine.

Ketamine for Non-Neuropathic Pain

Chronic pain is one of the leading causes of years lost to disability, as most of the time it is refractory to conventional treatment. Recent advances in understanding the pain mechanisms have favored the use of ketamine as a rescue agent in refractory chronic pain conditions, as it has potential modulating effect on both sensory-discriminative and affective motivational components of pain. Preclinical studies also suggested the antinociceptive effect of sub anesthetic dose of ketamine against central and peripheral neuropathic pain conditions and non-neuropathic pain conditions such as inflammatory and nociceptive pain states. Subanesthetic infusion of ketamine along with adjuvants such as midazolam and clonidine is found to reduce the psychomimetic and cardiovascular side effects of ketamine. Even though the consensus guidelines for intravenous use of ketamine for chronic pain advocate the use of ketamine only for complex regional pain syndrome, various other clinical studies suggested its role in other refractory painful conditions. Hence the present topic focuses specifically on the effect of ketamine on non-neuropathic pain conditions such as complex regional pain syndrome, fibromyalgia, headache, ischemic limb pain, etc. Many studies had shown that ketamine not only reduces the pain scores but also the analgesic medications, which further improves the well-being and quality of life.

Fms-like tyrosine kinase 3 is a regulator of the cardiac side population in mice

Fms-like tyrosine kinase 3 (Flt3) is a regulator of hematopoietic progenitor cells and a target of tyrosine kinase inhibitors. Flt3-targeting tyrosine kinase inhibitors can have cardiovascular side effects. Flt3 and its ligand (Flt3L) are expressed in the heart, but little is known about their physiological functions. Here, we show that cardiac side population progenitor cells (SP-CPCs) from mice produce and are responsive to Flt3L. Compared with wild-type, flt3L−/− mice have less SP-CPCs with less contribution of CD45−CD34+ cells and lower expression of genes related to epithelial-to-mesenchymal transition, cardiovascular development and stem cell differentiation. Upon culturing, flt3L−/− SP-CPCs show increased proliferation and less vasculogenic commitment, whereas Akt phosphorylation is lower. Notably, proliferation and differentiation can be partially restored towards wild-type levels in the presence of alternative receptor tyrosine kinase-activating growth factors signaling through Akt. The lower vasculogenic potential of flt3L−/− SP-CPCs reflects in decreased microvascularisation and lower systolic function of flt3L−/− hearts. Thus, Flt3 regulates phenotype and function of murine SP-CPCs and contributes to cellular and molecular properties that are relevant for their cardiovasculogenic potential.

Cardiovascular Side Effects of Chimeric Antigen Receptor (CAR) T-Cell Products: A Single Center Experience in a Minority Rich, Ethnically Diverse Real-World Cohort

Introduction: Axicabtagene ciloleucel (Axi-Cel), an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy demonstrated efficacy in patients with refractory large B cell lymphoma when conventional treatments failed. Cardiovascular side effects of CAR-T therapy that have been noticed so far include hypotension, left ventricular dysfunction, heart failure and cardiogenic shock in settings of CRS. We aimed to assess the cardiovascular side effects in a racially/ ethnically diverse patient population who underwent CAR-T cell therapy. Methods: This study included thirty-four consecutive adult patients who underwent treatment with CAR-T cell product Axi-Cel at an academic health system between 2018-2021. We performed detailed chart reviews and collected information related to the age, gender, hematological malignancy diagnosis, other medical comorbidities, therapeutic regimens, pretreatment cardiac risk factors, development of CRS with grading , pre and post treatment electrocardiograms ( EKG), transthoracic echocardiograms( TTE) , death, cause of death, and duration between administration of CAR-T products and death of the patients . We collected data pertaining to development of hypotension, EKG changes, arrhythmias, left ventricular systolic dysfunction, heart failure (HF), acute cardiac syndrome (ACS), troponin elevation, echocardiographic changes post CAR-T cell therapy, and follow up visits after 60 days to get information pertaining to development of hypotension, tachycardia or SOB, need for further cardiac work up, and cardiology referral. Results: Mean age of our study participants was 65 years ranging between ages of 30 and 84 years with 38 % (13/34) female and 62% (21/34) male study participants. Study population was predominantly Hispanic, white and African American with percentages of 35% (12/34), 32% (11/34), 26 %(9/34) respectively followed by categories Asian 2.9% (1/34) and other at 2.9 %( 1/34). Sixty seven percent (22/37) patients had primary diffuse large B cell lymphoma (DLBCL) and 32% (11/34) had different primary malignancy with transformation into DLBCL. Thirty eight percent individuals had received autologous stem cell transplant. Sixty one percent (21/34) of our study participants developed cytokine release syndrome, with CRS grades 1-3 in 57% (12/29), 25% (08/21) and 4.7% (1/21) respectively. Thirty four percent (09/34) study participants died after cellular therapy. Septic shock and disease progression each were primary cause of death in 55 % (5/9) of patients, followed by respiratory failure in 22% (2/9) and ventricular fibrillation leading to cardiac arrest in 11% (1/9) of the patients. Mean duration of time between administration of therapy and death was 70 days. The cardiovascular effects noted immediately post CAR-T treatment and observations from follow up oncology visits are listed in Table 1. Troponin elevation was noticed in two study participants in settings of CRS, but one participant exhibited troponin elevation in absence of CRS. Seventeen percent of patients (6/34) developed left ventricular dysfunction after Axi-Cel. Most of them had concurrent CRS but one case of fatal heart failure occurred in absence of CRS. Three patients developed fatal arrhythmias post CAR-T therapy (1- Non sustained ventricular tachycardia in settings of CRS, 2- supraventricular tachycardia in settings of CRS, and 3- ventricular tachycardia needing defibrillation without CRS). Only one patient developed ACS in settings of CRS which lead to patient's demise. Conclusions: In a real world, minority rich cohort, we observed that a significant number of our patients had preexisting cardiovascular findings including abnormal EKG (30% excluding sinus tachycardia) or abnormal echocardiographic findings (46%). Hypotension (68%) and sinus tachycardia (59%) were the most commonly observed cardiovascular toxicities. Although Axi-Cel was in general safe and well tolerated, we observed cardiovascular side effects associated with and independent of CRS. Notably, six patients (17%) developed left ventricular dysfunction including one fatality which was independent of CRS. There was only one fatal coronary syndrome and two cases of troponin elevation in our series. Our study stresses the importance of a thorough cardio-oncology evaluation before proceeding with cellular therapies as well as involved follow up during and after hospitalization. Figure 1 Figure 1. Disclosures Gritsman: iOnctura: Research Funding. Shastri: Kymera Therapeutics: Research Funding; Onclive: Honoraria; Guidepoint: Consultancy; GLC: Consultancy. Verma: BMS: Research Funding; GSK: Research Funding; Incyte: Research Funding; Medpacto: Research Funding; Curis: Research Funding; Eli Lilly: Research Funding; Stelexis: Consultancy, Current equity holder in publicly-traded company; Novartis: Consultancy; Acceleron: Consultancy; Celgene: Consultancy; Stelexis: Current equity holder in publicly-traded company; Throws Exception: Current equity holder in publicly-traded company.

Fexofenadine: review of safety, efficacy and unmet needs in children with allergic rhinitis

Allergic rhinitis (AR) is the most common undiagnosed chronic condition in children. Moderate/severe AR symptoms significantly impair quality of life, and cause sleep disruption, absenteeism and decreased productivity. Additionally, untreated AR predisposes children to asthma and other chronic conditions. Although intranasal corticosteroids are the most effective pharmacologic treatment for AR, oral antihistamines are often preferred. First-generation antihistamines may be chosen to relieve AR symptoms as they are inexpensive and widely available; however, they cause sedative and cardiovascular negative effects due to poor receptor selectivity. Therefore, second-generation antihistamines were developed to reduce adverse effects while retaining efficacy. There are fewer clinical trials in children than adults, therefore, efficacy and safety data is limited, particularly in children under 6 years, highlighting the need to generate these data in young children with AR. Fexofenadine, a highly selective second-generation antihistamine, effectively alleviates symptoms of AR, is non-sedating due to decreased blood–brain barrier permeability, and is devoid of cardiovascular side effects. Importantly, fexofenadine relieves the ocular symptoms of allergic conjunctivitis, which occur concomitantly with AR, improving quality of life. Overall, fexofenadine displays a favorable safety profile and results in greater treatment satisfaction in children compared with other second-generation antihistamines. This review aimed to evaluate and compare the safety and efficacy of fexofenadine with other available first- and second-generation antihistamines in children with AR.

Oxytocin as an Anti-obesity Treatment

Obesity is a growing health concern, as it increases risk for heart disease, hypertension, type 2 diabetes, cancer, COVID-19 related hospitalizations and mortality. However, current weight loss therapies are often associated with psychiatric or cardiovascular side effects or poor tolerability that limit their long-term use. The hypothalamic neuropeptide, oxytocin (OT), mediates a wide range of physiologic actions, which include reproductive behavior, formation of prosocial behaviors and control of body weight. We and others have shown that OT circumvents leptin resistance and elicits weight loss in diet-induced obese rodents and non-human primates by reducing both food intake and increasing energy expenditure (EE). Chronic intranasal OT also elicits promising effects on weight loss in obese humans. This review evaluates the potential use of OT as a therapeutic strategy to treat obesity in rodents, non-human primates, and humans, and identifies potential mechanisms that mediate this effect.

Remdesivir-Associated Significant Bradycardia: A Report of Three Cases

Recently, remdesivir was approved by the United States Food and Drug Administration for patients with Coronavirus disease 2019 (COVID-19). We herein describe 3 patients with COVID-19 who showed significant bradycardia and QTc prolongation after remdesivir administration. Bradycardia did not respond to atropine treatment in 2 of the patients, one of whom received theophylline and the other required a temporary pacemaker. Fortunately, the patients’ heart rate and rhythm returned to normal after the discontinuation of remdesivir, albeit it lengthened their hospital stays. Careful monitoring during remdesivir infusion may decrease the risk of adverse cardiovascular side effects.