Impact of Hypocalcemia on the Prognosis of Patients with Acute Myocarditis.

Acute viral myocarditis is a serious complication of viral infectious diseases, including coronavirus disease 2019 (COVID-19). To better understand the pathogenesis of acute viral myocarditis, we retrospectively analyzed the incidence and prognostic significance of hypocalcemia among patients with acute myocarditis, most of whom were considered to have acute viral myocarditis. We retrospectively reviewed the demographic and clinical data of patients with clinically confirmed acute myocarditis treated in our hospital over a 13-year period from 2006 to 2019, including laboratory results, cardiac imaging findings, and clinical outcomes. These data were compared between lower, middle, and higher calcium groups depending on the minimum calcium level measured during hospitalization. Among the 288 patients with acute myocarditis included, the hypocalcemia group (lower calcium group) had poorer clinical and laboratory results, received more medications and device support, and experienced poorer outcomes, including heart failure, arrhythmias, and death. Specifically, the left ventricular ejection fraction was significantly lower, and the length of hospital stay was significantly longer in the hypocalcemia group than in the other two groups. Furthermore, the incidence rates of atrioventricular block, ventricular tachycardia/ventricular fibrillation, cardiogenic shock, and mortality were significantly higher in the hypocalcemia group. Multivariate Cox regression analysis identified hypocalcemia as an independent risk factor for 30-day mortality in patients with acute myocarditis. In conclusion, the clinical evidence provided by the present study indicates that hypocalcemia is a risk factor for poorer outcomes in patients with acute myocarditis that should be considered carefully in the diagnosis and treatment of these patients.

Chronic Chilblain Like Lesions Associated with the Covid-19 Pandemic

Background/Aims We report the features of chronic chilblain-like digital lesions newly presenting since the start of the covid-19 pandemic. Comparison with primary perniosis and acrocyanosis, reveals a unique phenotype which appears to be a long-covid phenomenon. Methods The case records of 26 patients with new onset persistent chilblain-like lesions presenting to the Rheumatology service of St George's University Hospital, London between Autumn 2020 and Spring 2022 were reviewed. Demographic and clinical features, serology, imaging, treatment response and outcome up to Summer 2022 were collated retrospectively. Results Chilblain-like lesions first occurred between September and March;2019/ 2020 6 cases, 2020/2021 18 cases and 2021/2022 2 cases. Mean age 35.4 (17-60) years, 88% female, 85% white, all non-smokers. Median body mass index (BMI) 20.2, range 17.0 - 33.2. BMI underweight (<18.5) in 27%. All cases reported new red-purple-blue colour changes of the fingers, some with pain, swelling and pruritis, affecting both hands in 12, one hand in 6, and both hands and feet in 8 cases. There was a past history of cold sensitivity or primary Raynaud's in 54%. Covid was confirmed in 3 cases, 2 - 8 months prior to onset of chilblain-like symptoms. Possible covid, unconfirmed, was suspected in 5 cases, 1 - 11 months earlier. Affected digits appeared diffusely erythro-cyanotic in 81%, with blotchy discrete maculo-papular erythematous lesions in 42%, some with both features. Involvement was asymmetric in 54%, thumbs spared in 69%. Complement was low in 50% (8/16), ANA positive in 26% (6/23). MRI of hands showed phalangeal bone marrow oedema in keeping with osteitis in 4 of 7 cases. More severe signs and symptoms were associated with low BMI, low C3/4 and a past history of cold sensitivity or Raynauds. Cold avoidance strategies were sufficient for 58%. Pain prompted a trial of NSAIDs, aspirin, nitrates, calcium channel blockers, hydroxychloroquine, oral or topical corticosteroid or topical tacrolimus in 42%. In general, these were minimally effective or not tolerated. 4 severe cases received sildenafil or tadalafil, effective in 2. In 27% complete remission occurred during the first summer season after symptoms commenced, median duration 6 (range 2 - 10) months. In the remaining 19 cases, chilblain-like symptoms returned or worsened in the subsequent second winter period, with 6 of 19 entering remission the following summer. For the remaining 13 persistent cases the total duration of symptoms spans more than a year, and in four cases more than 2 years. Conclusion This series illustrates a distinct chronic chilblain-like condition. Features similar to primary perniosis include female predominance, middle age, pruritic painful blotchy lesions, asymmetry and low BMI. Features in keeping with acrocyanosis include chronicity, extensive diffuse erythro-cyanotic discoloration, relative improvement in warm weather and lack of association with smoking.

Global Collaboration to Provide Drug Interaction Guidance for Nirmatrelvir/Ritonavir

Background: Nirmatrelvir/ritonavir (NMV/r), a preferred antiviral for high-risk outpatients with COVID-19, is associated with major drug-drug interactions (DDIs). Given the lack of DDI data with short course ritonavir (RTV), initial NMV/r product information was extrapolated from chronic, full dose RTV use. In Jan 2022, DDI experts from the University of Liverpool (UoL), NIH COVID-19 Guidelines Panel, and Ontario Science Table (OST) contributors established a global collaboration to address DDI challenges limiting NMV/r use in real-life settings. We report how safe, pragmatic, and consistent resources were developed to support NMV/r prescribing, and the utilization of these resources globally. Method(s): The 3 teams met monthly to discuss DDIs, review NMV/r DDI literature, and achieve consensus on recommendations. Additional experts were invited as needed. Metrics from the UoL DDI checker guided review of most searched DDIs overall and by severity. 2022 usage metrics for each DDI guide were collected. Differences in recommendations between initial DDI guides and product information were compared. Result(s): In 2022, 12 meetings were convened. Each team's DDI guide was revised and expanded (Table 1). To factor in the lower RTV dose and shorter treatment duration, some recommendations differed from product information. Drug categories that required the most discussion and revision included: anticoagulants (ACs), immunosuppressants, calcium channel blockers. NMV/r accounted for 85% of queries on the UoL site. NMV/r DDI guidance was the most viewed page of the NIH guidelines and among the OST ID/clinical care Science Briefs. Top searched drugs on the UoL site with serious DDIs were certain ACs and statins. Utilization of DDI guides was not limited to in-country resources: 51% and 7% of UoL queries came from the USA and Canada, respectively. NIH users followed links to the UoL and OST sites 161,478 and 37,619 times, respectively. Conclusion(s): Significant efforts have been made by the 3 teams to provide upto-date, complementary DDI guidance. Usage metrics confirm the demand for DDI guidance during the pandemic. Cross-utilization of the DDI guides confirms the need for consistency. DDI recommendations were more permissive than initial product information, expanding clinicians' ability to prescribe NMV/r. DDI guidance for ACs and immunosuppressants was particularly challenging. During drug development, complex interactions likely to be encountered in target populations should be addressed.

Screening of Cardiovascular Disease's Risk Factors Among Community Pharmacies in Rural India

Introduction: The main prevention of cardiovascular disease (CVD) and healthcare cost reduction depend on the early identification and treatment of cardiovascular disease (CVD) risk factors through screening. Hypertension, obesity, a large waist circumference, smoking, poor diets, physical inactivity, and excessive alcohol consumption are well-known and potentially treatable risk factors for cardiovascular disease. This allows for early detection of instances, informs the start of CVD prevention medication, and is also very cost-effective. Method(s): At rural India, between March and August 2021, a cross-sectional survey was conducted in community pharmacies. One thousand two hundred healthy individuals were screened for signs of obesity, high blood pressure, waist circumference, and history of smoking and alcohol intake. A structured questionnaire was used to get participants' physical activity and diet. Result(s): The gender split of the 1200 participants who were screened was 67.8% male and 32.3% female. Participants' ages ranged from 18 to 60 years old in 43.3% of cases, 41 to 60 years old in 26.3%, and over 60 in 30.4% of cases. There were 43.7% of drinkers and 47.3% of smokers, respectively. A BMI of 25 kg/m2 or more indicates being overweight, whereas a BMI of 30 kg/m2 indicates being obese. Using a diagnostic cutoff of >140/90mmHg prevalence of hypertension was 44.3%, and 14.9% out of these were previously hypertensive. 31.5% had high waist circumference, 13.9% had insufficient physical activity, and 34.9% had insufficient intake of fruits and vegetables. Conclusion(s): The majority felt that screening for CVD risk factors was helpful, and more than one-fourth of the study participants had two or more CVD risk factors combined. A cost-effective strategy for the primary prevention of CVD that can have a positive influence on the healthcare delivery system is the capacity to further discover previously undetected risk factors.Copyright © 2023, Global Research Online. All rights reserved.

Evaluation of the Effect of Underlying Diseases on Mortality of COVID-19 Patients: A Study of 19,985 Cases

Background: The outbreak of a new coronavirus in China in 2019 (COVID-19) caused a global health crisis. Objective(s): This study was performed to investigate the effect of different underlying diseases on mortality in patients with COVID-19. Method(s): This retrospective cohort study was performed on COVID-19 patients admitted to the Shahid Rahimi and Sohada-ye Ashayer teaching hospitals in Khorramabad, Iran, from 2019 to 2021. Data on disease severity, clinical manifestations, mortality, and underlying disorders were collected and analyzed using the SPSS software version 22 at a 95% confidence interval and 0.05 sig-nificance level. Result(s): The study included 9653 men (48%) and 10332 women (52%). Patients with chronic kidney diseases, cancer, chronic obstruc-tive pulmonary disease, hypertension, cardiovascular disease, and diabetes were at higher mortality risk than those without these underlying diseases, respectively. However, there was no significant relationship between asthma and mortality. Also, age > 50 years, male gender, oxygen saturation < 93 on admission, and symptoms lasting <= 5 days were associated with increased mortality. Conclusion(s): Since patients with underlying diseases are at higher mortality risk, they should precisely follow the advice provided by health authorities and receive a complete COVID-19 vaccination series.Copyright © 2022, Author(s).

Evaluation of the Association between Multilobar Involvement and ACE Inhibitor Use in SARS-CoV-2 Patients

Aim: Angiotensin-converting enzyme 2 (ACE2) acts not only as an enzyme but also as a thought to be central receptor by which severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) enters host cells. Angiotensin-converting enzyme inhibitors (ACEIs) are thought to $1 are central to SARS-CoV-2 progression. However, its effect on clinical outcomes is still not fully explained. In this study, we investigated the effects of ACEIs use on pulmonary computed tomography findings. Method(s): The data of the patients who were hospitalized for SARS-CoV-2 pneumonia and were using medications for the diagnosis of hypertension from 20th March to 20th June 2020 were evaluated retrospectively. Patients were divided into 2 groups patients using ACEIs and not using ACEIs. Result(s): The study was conducted with 107 patients. Mild cases without signs of pneumonia were excluded from this study. Moderate cases were accepted as patients with symptoms related to the respiratory system and pneumonia detected on imaging. SpO2<=93%, >=30 breaths/min respiratory rate, and patients who developed respiratory failure, mechanical ventilator need, shock, or multiorgan failure were included in the severe and critically ill cases group. Severe and critical cases were evaluated as a single group. When the radiological images of the patients were examined, it was remarkable that multilobar findings were less common in the ACEIs using group (p<0.001). At the clinical end point, mortality rates in patients using ACEIs (12.7%) were significantly lower than patients without using ACEIs (32.7%). Conclusion(s): In our study, we showed that SARS-CoV-2 progresses with less multilobar involvement in pulmonary computed tomography in patients using ACEI.Copyright © 2023 by The Medical Bulletin of Istanbul Haseki Training and Research Hospital The Medical Bulletin of Haseki published by Galenos Yayinevi.

Beta-Blocker and Calcium Channel Blocker Toxicity With BRASH Syndrome: A Case Report.

Atrioventricular (AV) nodal blockers have a wide variety of medical uses, including the management of hypertension and cardiac arrhythmias. Like any other drug, they can carry side effects and toxicity. We present a case of a patient with a constellation of findings consistent with bradycardia, renal failure, AV nodal blockade, shock, and hyperkalemia (BRASH) syndrome. A 75-year-old female with a history of paroxysmal atrial fibrillation and heart failure with preserved ejection fraction presented to the hospital with shortness of breath. She was discharged two weeks prior to the presentation from another hospital after being treated for atrial fibrillation with a rapid ventricular response. She was discharged on metoprolol and diltiazem. Upon presentation to the hospital, the patient was noted to be bradycardic and hypotensive with blood work notable for acute kidney injury and hyperkalemia, consistent with BRASH syndrome. She received a dose of intravenous (IV) glucagon followed by infusion and received epinephrine infusion. Once clinically stable, she was discharged with her home dose of metoprolol and a reduced dose of diltiazem with a close follow-up with cardiology. Early recognition of BRASH syndrome as a unique clinical entity rather than different pathologic conditions is important to improve morbidity and mortality in these patients.

MALIGNANT HYPERTENSION AFTER COVD-19 VACCINE INJECTION

Case;40 y/o male. Clinical course;The patient was transferred to our university hospital because of DOE and severe headache. He had been well and had no history of hypertension or obesity. He had experienced the COVID-19 vaccine injection two week before this visit. After the injection he had been experienced high fever and general fatigue as well as 7 kg of weight loss. On examnation, it was found that he had severe hypertension (190/110 mmHg) and hypertensive optic fundi. On chest X-ray, cardiomegaly and bilateral lung infiltrations was evident and biochemical data indicated renal dysfunction (serum creatinine 2.35 mg/dl), high levels of plasma renin activity (39.1 ng/ml/hour normal;0.6-3.9) and aldosterone concentration (176 pg/ml normal;4.0-82.1), and inflammatory changes (CRP = 23 mg/dl). We also found that increased levels of LDH and decreased levels of hemoglobin which indicated hemolytic anemia and thrombotic microangiopathy. After the control of high blood pressure by intravenous administration of Calcium channel blockades, We performed renal biopsy, which had a finding of diffuse findings of onion skin lesion and global glomerular sclerosis compatible with the diagnosis of malignant hypertension. Any secondary etiologies including renal artery disease or collagen disease had not been identified. Seven days after the admission, we started hemodialysis for this patient because of the renal failure was not resolved. We also had startred ACE inhibitors. We stopped the diuretics and minimized the ultrafiltration. Twenty-five days after the admission the patients was withdrawn from dialysis with the urine volume around 2000 ml/day and the serum creatinine concentration 5.29 mg/dl. He was discharged without any aid of dialysis and with small number of anti-hypertensives. Four months after the discharge, his serum creatinine concentration was 3.36 mg/dl and his blood pressure was 139/85 mmHg with the ACE inhibitor and calcium channel blockades. Conclusions;The case suggested that the malignant hypertension might be triggered by COVID-19 vaccine injection, which is of clinical importance.

RENIN-ANGIOTENSIN-ALDOSTERONE SYSTEM INHIBITORS VERSUS CALCIUM CHANNEL BLOCKERS IN ASSOCIATION WITH MORTALITY RATE IN COVID-19 HYPERTENSIVE PATIENTS: THE EFFECT OF AGE

Objective: To study the association of calcium channel blockers (CCBs), the renin-angiotensin-aldosterone system (RAAS) inhibitors or their combination as antihypertensive medications and the clinical outcome of COVID-19 infection. Design and method: This is a retrospective cohort study using de-identified data retrieved from clinical records of COVID-19 patients in two isolation centers. Medical history, demographic data, symptoms, complications and laboratory investigations were extracted from clinical records of 406 confirmed COVID-19 hospitalized patients between Feb 2020 and July 2021. Hypertension and antihypertensive treatments were confirmed by medical history and clinical records. Continuous variables were presented as means ± standard deviation (SD) while categorical variables were presented as percent proportions. Logistic regression was used to assess the impact of antihypertensive drugs (RAAS inhibitors, CCBs, combination of RAAS inhibitors and CCBs and those not receiving medication) on the prognosis of COVID-19 patients and to explore the risk factors associated with mortality. Result: Out of 406 hospitalized COVID-19 patients, 242 (59.6%) had a history of hypertension. Hypertensive patients under the age of 65 years and receiving RAAS inhibitors or the combination of both RAAS inhibitors and CCBs were at higher risk of mortality than those on CCBs only (odds ratio [OR]: 4.45, 95% confidence interval [CI]: 1.56-12.56, P = 0.005 and OR:3.57, CI: 1.03-12.36, P = 0.045 respectively). Antihypertensive medications did not seem to influence mortality rates among hypertensive patients above 65 years. Routine laboratory investigations were not significantly different between the subgroups receiving different antihypertensive medications regardless of age. Cough was the only symptom associated with mortality among patients under 65 years (OR:2.34, CI:1.24-4.41, P = 0.009). Type II respiratory failure was significantly associated with death among hypertensives under 65 years (OR:5.43, CI:1.08-28.07, P = 0.044) whereas acute kidney injury and septic shocks are the common complications related to death among hypertensives above 65 years (OR:3.59, CI:1.54-8.36, P = 0.003 and OR:7.87, CI: 1.68-36.78, P = 0.009 respectively). Conclusion: Administration of CCBs may improve the outcome of COVID-19 hypertensive patients under 65 years of age. Antihypertensive treatment does not seem to influence the prognosis of COVID-19 patients above 65 years. Such results may affect management strategy of COVID-19 hypertensive patients. Type-II respiratory failure among patients under 65 years of age, acute kidney injury and septic shock among those above 65 years are the most serious complications that can lead to death regardless of blood pressure.

The key role of Calpain in COVID-19 as a therapeutic strategy.

COVID-19 is one of the viral diseases that has caused many deaths and financial losses to humans. Using the available information, this virus appears to activate the host cell-death mechanism through Calpain activation. Calpain inhibition can stop its downstream cascade reactions that cause cell death. Given the main roles of Calpain in the entry and pathogenicity of the SARS-CoV-2, its inhibition can be effective in controlling the COVID-19. This review describes how the virus activates Calpain by altering calcium flow. When Calpain was activated, the virus can enter the target cell. Subsequently, many complications of the disease, such as inflammation, cytokine storm and pulmonary fibrosis, are caused by virus-activated Calpain function. Calpain inhibitors appear to be a potential drug to control the disease and prevent death from COVID-19.

Therapeutic target and clinical impact of day-to-day blood pressure variability in hypertensive patients with covid-19.

Blood pressure variability (BPV) is essential in hypertensive patients and is frequently associated with organ damage. As of today, hypertension is still the most common comorbidity in COVID-19, but the impact of BPV and the therapeutic target of BPV on outcomes in COVID-19 patients with hypertension remain unclear. Therefore, this study investigated the relationship between BPV and severity of COVID-19, in-hospital mortality, hypertensive status, and efficacy of antihypertensives in suppressing hypertensive covid-19 patient BPV. This cohort retrospective study enrolled 351 patients hospitalized with COVID-19. Subjects were classified according to the severity of COVID-19, the presence of hypertension, and their BPV status. During hospitalization, mean arterial pressure (MAP) was measured at 6 a.m. and 6 p.m., and BPV was calculated as the coefficient of variation of MAP (MAPCV). MAPCV values above the median were defined as high BPV. In addition, we compared the hypertensive status, COVID-19 severity, in-hospital mortality, and antihypertensive agents between the BPV groups. The mean age was 53.85 ± 18.84 years old. Hypertension was significantly associated with high BPV with prevalence ratio (PR) = 1.38 (95% CI = 1.13-1.70; p = 0.003) or severe COVID-19 (PR = 1.39; 95% CI = 1.09-1.76; p = 0.005). In laboratory findings, high BPV group had lower Albumin, higher WBC, serum Cr, CRP, and creatinine to albumin ratio. High BPV status also significantly increased risk of mortality (HR = 2.30; 95% CI = 1.73-3.86; p < 0.001). Patients with a combination of severe COVID-19 status, hypertension, and high BPV status had the highest risk of in-hospital mortality (HR = 3.51; 95% CI = 2.32-4.97; p < 0.001) compared to other combination status groups. In COVID-19 patients with hypertension, combination therapy with calcium channel blockers (CCB) as well as CCB monotherapy significantly develop low BPV (PR = 2.002; 95 CI% = 1.33-3.07; p = 0.004) and low mortality (HR = 0.17; 95% CI = 0.05-0.56; p = 0.004). Hypertensive status and severe COVID-19 were significantly associated with high BPV, and these factors increased in-hospital mortality. CCBs might be antihypertensive agents that potentially effectively suppressing BPV and mortality in COVID-19 patients.

Impact of the COVID-19 pandemic on cardiovascular heart disease medication use: time-series analysis of England's prescription data during the COVID-19 pandemic (January 2019 to October 2020).

BACKGROUND: Management of high blood pressure (BP) typically requires adherence to medication regimes. However, it is known that the COVID-19 pandemic both interrupted access to some routine prescriptions and changed some patient health behaviours. AIM: This study, therefore, retrospectively investigated prescription reimbursement of cardiovascular (CVD) medicines as a proxy measure for patient adherence and access to medicines during the pandemic. METHODS: A cohort study of all primary care patients in England prescribed CVD medicines. The exposure was to the global pandemic. Prescriptions were compared before and after the pandemic's onset. Statistical variation was the outcome of interest. RESULTS: Descriptive statistics show changes to monthly prescriptions, with wide confidence intervals indicating varying underlying practice. Analysis of variance reveals statistically significant differences for bendroflumethiazide, potassium-sparing diuretics, nicorandil, ezetimibe, ivabradine, ranolazine, colesevelam and midodrine. After the pandemic began (March-October 2020), negative parameters are observed for ACE inhibitors, beta-blockers, calcium channel blockers, statins, antiplatelet, antithrombotics, ARBs, loop diuretics, doxazosin, bendroflumethiazide, nitrates and indapamide, indicating decelerating monthly prescription items (statistically significant declines of calcium channel blockers, antithrombotic, adrenoreceptor blockers and diuretics) of CVD medicines within the general population. Many data points are not statistically significant, but fluctuations remain clinically important for the large population of patients taking these medications. CONCLUSION: A concerning decline in uptake of CVD therapies for chronic heart disease was observed. Accessible screening and treatment alongside financial relief on prescription levies are needed. A video abstract is (4 min 51 s) available: https://bit.ly/39gvEHi.

BOOZE, BETAS, AND A FATTY SOLUTION TO SPARE PANDEMIC WOES

SESSION TITLE: Cases of Overdose, OTC, and Illegal Drug Critical Cases Posters SESSION TYPE: Case Report Posters PRESENTED ON: 10/17/2022 12:15 pm - 01:15 pm INTRODUCTION: The COVID-19 pandemic raised economic strife, social isolation, fear from contagion, and anxiety to a level where 45% of surveyed U.S. adults report a detriment to their mental health. With U.S. suicide rates up from 10 to 14 cases per 100,000 over the past 20 years, the health and safety of a vulnerable mental health population becomes more of a concern. We report a case of an individual with depression who was resuscitated after severe toxicity from alcohol and beta-blocker ingestions. CASE PRESENTATION: A 58-year-old woman with prior suicide attempts was found in an obtunded state after finishing a 20-pack of beer and swallowing a propranolol 20 mg pill bottle. On admission, she presented with bradycardia, hypotension, and alteration to a Glasgow Coma Scale of 9 with emesis residue on her face. Her blood gas revealed an anion-gap metabolic acidosis with a pH of 7.26, lactate of 2.53, normal potassium and calcium, and glucose of 134 mg/dL. Toxicity labs were notable for an alcohol of 199 mg/dL. Her EKG demonstrated a junctional bradycardia with a p-wave complex after the QRS consistent with retrograde depolarization of the atrium (Image 1). She was intubated to protect her airway. She subsequently developed cardiac arrest secondary to pulseless electrical activity. She underwent CPR for 33 minutes with boluses of intravenous epinephrine, glucagon, insulin, calcium gluconate, and sodium bicarbonate prior to return of spontaneous circulation. Due to failure of transcutaneous pacing, a transvenous pacer was placed. In concert with Poison Control, she was started on an a euglycemic insulin drip and an intralipid infusion. Her hemodynamics improved, and she was weaned off pacing and ICU interventions within 24 hours. She was discharged a week after admission with no residual morbidities. DISCUSSION: Overdose from nonselective beta-blockers can result in bradycardia, hypotension, seizures, QRS widening, QTc prolongation with ventricular tachy-arrhythmias, hyperkalemia, and hypoglycemia. Understanding the pharmacodynamics of beta-blocker toxicity enables targeted interventions to improve: chronotropy with epinephrine, glucagon, and pacing;inotropy with insulin, calcium, glucagon, and phosphodiesterase inhibitors;QRS widening with sodium bicarbonate;and QTc prolongation with magnesium or lidocaine. The high lipid solubility of propanol allows for intravenous lipid infusions to aid in drug elimination for patients in refractory cardiogenic shock. CONCLUSIONS: Despite a lack of labs for monitoring beta blocker toxicity, our case demonstrates successful resuscitation in a severe overdose. Perhaps an absence of hyperkalemia, hypoglycemia, QRS and QTc changes, and tachy-arrhythmias in this incident portended to a decreased morbidity and mortality. Ultimately, we reaffirmed the role of intralipid infusions as a critical treatment adjunct for recovery from cardiogenic shock secondary to beta blockade. Reference #1: Sher L. The impact of the COVID-19 pandemic on suicide rates. QJM. 2020;113(10):707-712. Reference #2: Kerns W 2nd. Management of beta-adrenergic blocker and calcium channel antagonist toxicity. Emerg Med Clin North Am. 2007;25(2):309-viii. Reference #3: Anderson AC. Management of beta-adrenergic blocker poisoning. Clin Pediatr Emerg Med. 2008;9(1):4–16. DISCLOSURES: No relevant relationships by Jackie Hayes No relevant relationships by Andrew Salomon

BETA BLOCKER AND CALCIUM CHANNEL BLOCKER OVERDOSE COMPLICATED BY COVID-19 PNEUMONIA AND RENAL FAILURE IN A PATIENT WITH SEVERE OBESITY

SESSION TITLE: A Look Into Poisoning and Drug Overdoses SESSION TYPE: Rapid Fire Case Reports PRESENTED ON: 10/18/2022 12:25 pm - 01:25 pm INTRODUCTION: We present a case of a 64-year-old woman with severe obesity (BMI 53) who presented with shock after beta-blocker (BB) and calcium channel-blocker (CCB) overdose. CASE PRESENTATION: The patient presented after an intentional suicide attempt, taking multiple antihypertensive medications, including tablets of nifedipine 90mg, carvedilol 25mg, and losartan 100mg. She had also been experiencing shortness of breath and lower extremity pain for several days. Upon arrival, she was lethargic and minimally responsive, and was found to be in shock with a heart rate 63. She was intubated for airway protection and started on multiple vasopressors including norepinephrine, phenylephrine, vasopressin, dopamine and epinephrine for circulatory support. She was also found to be positive for SARS-CoV-2. She was given activated charcoal, received gastric lavage, and whole bowel irrigation. She received a bolus of regular insulin at 1U/kg, and subsequently started on a high-dose insulin infusion titrated to 11U/kg/h along with dextrose infusion and calcium gluconate. By day four of admission, vasopressor requirements had been reduced to only norepinephrine and the insulin infusion had been successfully discontinued. However, her hospital course was further complicated MRSA and Pseudomonas pneumonia, and renal failure requiring hemodialysis. She continued to develop refractory shock, and remained over 50 liters net positive. Her condition progressively deteriorated and her gross volume overload was difficult to manage, and ultimately expired on day ten of admission. DISCUSSION: The management of CCB and BB overdose has been studied, with hyperinsulinemic euglycemic therapy (HIET)1,2 as our choice. Our patient's decline was likely secondary to the high volumes of dextrose infusion required after HIET. With underlying renal failure, insulin clearance proved to be a significant challenge. Such severe obesity with a weight-based regimen resulted in over 1500U insulin/hr at any given point with our patient. Renal clearance is governed by a proportion of t/V, where t denotes length of a dialysis session and V the volume of fluid in the patient's body.3 Patients with significant volume would require extensive dialysis sessions and fluid balances would be challenging. Continuous renal replacement therapy (CRRT) was attempted later in her hospital course. However, the patient was not able to tolerate it as she had progressed to multiorgan failure. CONCLUSIONS: HIET has shown to be a successful management strategy for CCB and BB overdose. However, weight-based dosing can prove to be a challenge in patients with severe obesity. CRRT should be considered early in severely obese patients that undergo HIET, given the rapid accumulation of fluid secondary to the large-volume insulin and dextrose infusions. Further investigations should look into identifying maximal safe dosages of HIET, especially in severely obese patients. Reference #1: Cole JB, Arens AM, Laes JR, Klein LR, Bangh SA, Olives TD. High dose insulin for beta-blocker and calcium channel-blocker poisoning. Am J Emerg Med. 2018 Oct;36(10):1817-1824. doi: 10.1016/j.ajem.2018.02.004 Reference #2: Krenz JR, Kaakeh Y. An Overview of Hyperinsulinemic-Euglycemic Therapy in Calcium Channel Blocker and β-blocker Overdose. Pharmacotherapy. 2018 Nov;38(11):1130-1142. doi: 10.1002/phar.2177 Reference #3: Turgut F, Abdel-Rahman E, M: Challenges Associated with Managing End-Stage Renal Disease in Extremely Morbid Obese Patients: Case Series and Literature Review. Nephron 2017;137:172-177. doi: 10.1159/000479118 DISCLOSURES: No relevant relationships by Alejandro Garcia No relevant relationships by Vishad Sheth no disclosure on file for Andre Sotelo;

Elucidating the role of the L-type calcium channel in excitability and energetics in the heart: The ISHR 2020 Research Achievement Award Lecture.

Cardiovascular disease continues to be the leading health burden worldwide and with the rising rates in obesity and type II diabetes and ongoing effects of long COVID, it is anticipated that the burden of cardiovascular morbidity and mortality will increase. Calcium is essential to cardiac excitation and contraction. The main route for Ca2+ influx is the L-type Ca2+ channel (Cav1.2) and embryos that are homozygous null for the Cav1.2 gene are lethal at day 14 postcoitum. Acute changes in Ca2+ influx through the channel contribute to arrhythmia and sudden death, and chronic increases in intracellular Ca2+ contribute to pathological hypertrophy and heart failure. We use a multidisciplinary approach to study the regulation of the channel from the molecular level through to in vivo CRISPR mutant animal models. Here we describe some examples of our work from over 2 decades studying the role of the channel under physiological and pathological conditions. Our single channel analysis of purified human Cav1.2 protein in proteoliposomes has contributed to understanding direct molecular regulation of the channel including identifying the critical serine involved in the "fight or flight" response. Using the same approach we identified the cysteine responsible for altered function during oxidative stress. Chronic activation of the L-type Ca2+ channel during oxidative stress occurs as a result of persistent glutathionylation of the channel that contributes to the development of hypertrophy. We describe for the first time that activation of the channel alters mitochondrial function (and energetics) on a beat-to-beat basis via movement of cytoskeletal proteins. In translational studies we have used this response to "report" mitochondrial function in models of cardiomyopathy and to test efficacy of novel therapies to prevent cardiomyopathy.

METFORMIN USE IS ASSOCIATED WITH LESS FREQUENT SEVERE LIVER INJURY UPON HOSPITAL ADMISSIN WITH COVID-19

Introduction In a study involving > 10,000 patients hospitalized with COVID-19, we found that liver injury, which was present in ~70% of patients upon hospital admission, correlates with in-hospital mortality (Satapathy et al., Eur J Gastroenterol Hepatol 2021). Curiously, severe liver chemistry abnormalities (LCA) were seen less often in patients with diabetes or hypertension, although these diseases confer increased risk of severe disease. This raises the question whether home medications protect from COVID-19 associated liver injury. We now analyzed associations between LCA and twenty-six groups of antidiabetic, antihypertensive, and other common mediations. Results 9898 patients hospitalized with COVID-19 in 13 hospitals in New York between March 1 to August 31, 2020, who had an complete records on admission were retrospectively analyzed. LCA measured were alanine and aspartate aminotransferases, alkaline phosphatase, and bilirubin, and were defined as absent, mildmoderate (up to four times elevated), or severe. Diseases and socioeconomic factors were similar to the initial study. 67.2% had hypertension, and 40.8% had diabetes. The most common medications included insulin (12.2%), metformin (18.3%), sulfonylureas (6.8%), DDP4 inhibitors (6.3%), ACE inhibitors (14.8%), ARBs (18.6%), beta-blockers (33.2%), calcium-channel blockers (26.5%), diuretics (21.6%), statins (41.5%), PPIs (22.1%), H2- blockers (6.8%), antiplatelets (31.0%), anticoagulants (20.5%). Comparisons between groups were analyzed using Kruskal-Wallis test, chi-squared test, and Fisher's exact test. Univariate and multivariate regression analysis were performed. Univariate analysis showed a higher risk for severe LCA in men, Asian and Black race, non-Hispanic ethnicity. As in our prior analysis, hypertension and diabetes were associated with less frequent severe LCA. In addition, hyperlipidemia, CAD, CHF, atrial fibrillation, CKD, ESRD, GERD, asthma, COPD, cancer, and liver disease were inversely associated with severe LCA. Medications that were associated with less frequent severe LCA included statins, ACE, ARBs, calcium-channel blockers, betablockers, diuretics, antiplatelet medications, insulin, biguanide, sulfonylureas, PPIs, H2- blockers, and anticoagulants, but not oral steroids. In multivariate analysis, male gender, Asian and Black race were associated with increased risk of severe LCA. Hypertension, ESRD and asthma were associated with less frequent severe LCA, but not diabetes. Among medications, only metformin showed a statistically significant correlation with severe LCA on admission, with a hazard ratio 0.57 (p 0.0002). Conclusions Metformin use was inversely associated with severe liver chemistry abnormalities upon hospital admission with COVID- 19 in a large cohort of patients during the initial pandemic in New York.

Managing Delirium in a patient with Extracorporeal Membrane Oxygenation (ECMO) machine for bridge to lung transplant: A Case report

Background: Due to COVID pandemic, there have been increased needs for ECMO circuits to support patients with respiratory failure1. Unfortunately, due to pharmacokinetics alteration of commonly used sedative and psychotropic medications by the ECMO circuits2,new sedation approaches to manage delirium and agitation is required. We present a case of COVID pneumonia patient on ECMO support, whose delirium symptoms were managed with a novel psychopharmacotherapy protocol. Case: Mr. M is a 57-year-old male patient with past medical history of obesity, hypertension, admitted to Stanford Hospital due to COVID pneumonia, complicated by respiratory failure, required to be on Veno-Venous ECMO support with bridge to transplant. He had significant hyperactive delirium with Richmond Agitation-Sedation Scale (RASS) score of +3 and ICDSC score of 7 for most of the days, despite heavy conventional pharmacological sedation. We observe the same problems with most patients placed on the ECMO system, leading to an investigation and development of a new protocol. Discussion: Patient on ECMO support requires adequate sedation to prevent clinical deterioration that can result from hyperactive delirium (ie., chugging, blood clots or decannulation)2. Nevertheless, ECMO circuit’s significant alterations of drug pharmacokinetics, such as increased volume of distribution and sequestration of lipophilic and protein bound medications, with no clear guidelines on managing sedation/delirium in patients with ECMO support at this time2, we conducted an extensive literature search and developed a novel protocol. This new sedation approach includes alpha-2 agonists, opioids, barbiturates and calcium channel modulators with the lowest lipophilicity and protein binding potential of each medication in its class4,5,thus overcoming the challenges introduced by ECMO circuits. The new protocol allowed the patient to participate in lung transplant work-up, physical therapy, and eventually facilitated receiving bilateral lung transplantation. Conclusion/Implications: ECMO is a life saving device that can help patient with cardiac-respiratory failure, and its use has been increasing in clinical practice. However, there needs to be an improvement in successful sedation/delirium management to minimize adverse events, and optimize the success of this lifesaving technologies. References: 1. Cho HJ, et al. ECMO use in COVID-19: lessons from past respiratory virus outbreaks-a narrative review. Crit Care. 2020 Jun 6;24(1):301 2. deBacker J, et al. Sedation Practice in Extracorporeal Membrane Oxygenation-Treated Patients with Acute Respiratory Distress Syndrome: A Retrospective Study. ASAIO J. 2018 Jul/Aug;64(4):544-551 3. Lemaitre F, et al. Propofol, midazolam, vancomycin and cyclosporine therapeutic drug monitoring in extracorporeal membrane oxygenation circuits primed with whole human blood. Crit Care. 2015;19(1):40 4. Hansch C, et al. Hydrophobicity and central nervous system agents: on the principle of minimal hydrophobicity in drug design. J Pharm Sci. 1987 Sep;76(9):663-87 5. Bockbrader HN, et al. A comparison of the pharmacokinetics and pharmacodynamics of pregabalin and gabapentin. Clin Pharmacokinet. 2010 Oct;49(10):661-9

IMPACT OF ANTIHYPERTENSIVE TREATMENT IN COVID-19 PATIENTS IN A TERTIARY CARE HOSPITAL

Background: Arterial hypertension has been described as one of the main risk factors for poor prognosis in Covid-19. In this context, the role of angiotensin-converting enzyme 2 (ACE2) in this infection has been studied, with studies showing how this enzyme acts as a functional receptor for SARS-CoV-2, favoring the penetration of the virus into the cell. The main objective of this work is to study the impact of chronic antihypertensive treatment in a cohort of SARS-CoV-2 positive patients with arterial hypertension, as well as clinical outcomes during hospitalization. Method: Single-center observational retrospective cohort study conducted at a tertiary level university hospital from 1st March 2020 to 31st May 2020. All adult patients admitted with a diagnosis of COVID-19 and a history of arterial hypertension on chronic treatment with an antihypertensive drug during the three months prior to contracting the infection were included. For the analysis, patients were divided into three groups according to the chronic antihypertensive treatment they were receiving: angiotensin-converting enzyme inhibitors (ACE inhibitors), angiotensin II receptor antagonists (ARB) or other treatment, excluding those patients who during the three months prior to the start of the study had been on concomitant treatment with ACE inhibitors and ARB, as well as those on treatment with more than four antihypertensive drugs. Results: A total of 475 cases with positive PCR for SARS-CoV-2 cases had hypertension as an associated comorbidity on antihypertensive treatment in the three months prior to admission. The mean age of this cohort of patients was 77.05 (SD 10.95) years, most of them male (56.8%) Regarding the prolonged length of stay variable, 127 patients (26.7%) were admitted for 14 days or more, with no statistically significant differences between the three groups. For patients admitted to the Intensive Care Unit (ICU) (29 patients, 6.1%) no differences were observed between the three study groups either.Regarding the outcome variable, all-cause in-hospital mortality, no statistically significant differences were observed between the groups (p = 0.836). Conclusions: Patients admitted with SARS-CoV2 respiratory infection with a diagnosis of hypertension and pre-admission treatment with an antihypertensive drug showed no statistically significant differences in mortality between those hypertensive patients who received renin-angiotensin-aldosterone system (RAAS) inhibitor antihypertensive drugs and those who received other antihypertensive treatments.

Renin-Angiotensin Aldosterone System Inhibitors and COVID-19: A Systematic Review and Meta-Analysis Revealing Critical Bias Across a Body of Observational Research.

Background Renin-angiotensin aldosterone system (RAAS) inhibitor-COVID-19 studies, observational in design, appear to use biased methods that can distort the interaction between RAAS inhibitor use and COVID-19 risk. This study assessed the extent of bias in that research and reevaluated RAAS inhibitor-COVID-19 associations in studies without critical risk of bias. Methods and Results Searches were performed in MEDLINE, EMBASE, and CINAHL databases (December 1, 2019 to October 21, 2021) identifying studies that compared the risk of infection and/or severe COVID-19 outcomes between those using or not using RAAS inhibitors (ie, angiotensin-converting enzyme inhibitors or angiotensin II type-I receptor blockers). Weighted hazard ratios (HR) and 95% CIs were extracted and pooled in fixed-effects meta-analyses, only from studies without critical risk of bias that assessed severe COVID-19 outcomes. Of 169 relevant studies, 164 had critical risks of bias and were excluded. Ultimately, only two studies presented data relevant to the meta-analysis. In 1 351 633 people with uncomplicated hypertension using a RAAS inhibitor, calcium channel blocker, or thiazide diuretic in monotherapy, the risk of hospitalization (angiotensin-converting enzyme inhibitor: HR, 0.76; 95% CI, 0.66-0.87; P<0.001; angiotensin II type-I receptor blockers: HR, 0.86; 95% CI, 0.77-0.97; P=0.015) and intubation or death (angiotensin-converting enzyme inhibitor: HR, 0.64; 95% CI, 0.48-0.85; P=0.002; angiotensin II type-I receptor blockers: HR, 0.74; 95% CI, 0.58-0.95; P=0.019) with COVID-19 was lower in those using a RAAS inhibitor. However, these protective effects are probably not clinically relevant. Conclusions This study reveals the critical risk of bias that exists across almost an entire body of COVID-19 research, raising an important question: Were research methods and/or peer-review processes temporarily weakened during the surge of COVID-19 research or is this lack of rigor a systemic problem that also exists outside pandemic-based research? Registration URL: www.crd.york.ac.uk/prospero/; Unique identifier: CRD42021237859.

NEW ONSET OF HYPERTENSION IN PATIENTS ADMITTED FOR INFECTION WITH SARS-COV-2 VIRUS

Objective: The aim of the study was to assess the clinical particularities and the lab tests in patients hospitalized for SARS-COV2 infection, with new onset of hypertension on admission. Design and method: We performed a retrospective study on 217 patients admitted to a Clinical Emergency Hospital between January 2021 and October 2021. Results: We had 217 patients admitted in internal medicine clinic for infection with SARS-COV2 virus, most of them with moderate and severe form of disease. From them, 148 patients had hypertension, 83.78% with medical history of hypertension and 16.22% with new onset of high blood pressure on admission. Patients were aged between 23 and 99 years, with an average age of 65 years. In comparison, the patients with new onset of hypertension (subgroup 1) were aged between 37 and 90 years, with an average age of 66 years. The most affected group of age was 60-69 years. In subgroup 1, the gender distribution was: 58.33% male, 41.66% female. At admission, the stages of SARS-COV2 infection in subgroup 1, according to CT examination, were severe in 52.38%, moderate 19.04%, and mild 28.57% of patients. As comorbidities in subgroup 1: cancer in 8.33%, metabolic syndrome 54.16%, dyslipidemia 4.16%, obesity 50%, type II diabetes mellitus 45.83%, chronic heart failure in 12.5% of cases (37.5% NYHA I class, 54.16% NYHA II class and 8.3% NYHA III class), atrial fibrillation in 12.5%, atherosclerosis in 16.66%, anxiety disorders in 4.16% and dementia in 8.33% of cases. High levels of inflammatory markers in Subgroup 1: CRP in 95.83%, procalcitonin in 87.5%, ferritin 79.16%, D-dimers in 83.33%, troponin 4.16%, NT-proBNP in 50% of cases. Decreased GFR was found in 65.21% of patients. Microalbuminuria was present in 29.16% of patients. The antihypertensive medication during hospitalization was: diuretics in 45.83%% of cases, betablockers in 33.34%, calcium blockers in 8.33%, angiotensin converting enzyme inhibitors in 16.67%. Conclusions: Hypertension with new onset during SARS-COV2 infection and its persistence in post-covid syndrome may have complex pathogenic mechanisms and require personalized therapeutic decision.