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Omar A Alshaya,1– 3 Arwa Alhamed,3,4 Sara Althewaibi,1 Lolwa Fetyani,1 Shaden Alshehri,1 Fai Alnashmi,1 Shmeylan Alharbi,1– 3 Mohammed Alrashed,1– 3,5 Saleh F Alqifari,6 Abdulrahman I Alshaya1– 3 1Department of Pharmacy Practice, College of Pharmacy, King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia; 2Department of Pharmaceutical Care, Ministry of National Guard-Health Affairs, Riyadh, Saudi Arabia; 3King Abdullah International Medical Research Center, Riyadh, Saudi Arabia; 4College of Nursing, King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia; 5Pharmacy Department, Northwest Medical Center, Tucson, AZ, USA; 6Department of Pharmacy Practice, College of Pharmacy, University of Tabuk, Tabuk, Saudi ArabiaCorrespondence: Omar A Alshaya, Department of Pharmacy Practice, College of Pharmacy, King Saud bin Abdulaziz University for Health Sciences, P.O. Box 3660, Riyadh, 11481, Saudi Arabia, Email omaraalshaya@gmail.comAbstract: Calcium channel blockers (CCBs) are widely prescribed medications for various clinical indications in adults and children. They are available in both immediate and long-acting formulations and are generally classified into dihydropyridines and nondihydropyridines, with nondihydropyridines having more cardioselectivity. CCB toxicity is common given the widespread use which leads to serious adverse clinical outcomes, especially in children. Severe CCB toxicities may present with life-threatening bradycardia, hypotension, hyperglycemia, and renal insufficiency. Dihydropyridine toxicity, however, may present with reflex tachycardia instead of bradycardia. Initial patient evaluation and assessment are crucial to identify the severity of CCB toxicity and design the best management strategy. There are different strategies to overcome CCB toxicity that requires precise dosing and close monitoring in various patient populations. These strategies may include large volumes of IV fluids, calcium salts, high insulin euglycemia therapy (HIET), and vasopressors. We hereby summarize the evidence behind the management of CCB toxicity and present a practical guide for clinicians to overcome this common drug toxicity.Keywords: calcium channel blockers, drug overdose, poisoning, emergency medicine, toxicity

Introduction: Traumatic brain injury (TBI) is a leading cause of mortality and morbidity worldwide. In addition, TBI may cause paroxysmal sympathetic hyperactivity (PSH), which is associated with poor clinical outcomes. This study aimed to evaluate the safety and effectiveness of clonidine in patients with TBI and suspected PSH., Methods: A retrospective cohort study for critically ill patients with TBI with suspected PSH admitted to intensive care units (ICUs) from 1 May 2016 to 31 January 2020 at a tertiary academic medical center. Eligible patients were categorized based on clonidine use during their ICU stay (Clonidine group vs. Control group). The primary outcome was the improvement in functional outcomes during ICU stay, defined by a delta Glasgow Coma Score (GCS). Secondary outcomes included ICU and hospital length of stay, heart rate variation, and 90-day mortality., Results: A total of 2915 patients were screened, of which 169 were included. Based on multiple regression analysis, patients who received clonidine showed better improvement in functional outcomes by a higher mean delta GCS than patients who did not (Beta Coeff. 0.41; CI: 0.07 - 0.74; P = 0.02). In addition, the patient's GCS upon ICU discharge and IV opioids requirement on day three were higher in the clonidine group than control (beta coefficient (95% CI): 0.18 (0.03, 0.32); p = 0.02 and beta coefficient (95% CI): 1.38 (0.24, 2.52); p = 0.02, respectively). No statistical differences were observed in any of the other secondary outcomes after adjusting for confounders., Conclusion: This study found that patients who received clonidine had better functional outcomes during their ICU stay, as shown by their delta GCS than those who did not. Other outcomes were similar between the groups. More data are needed to explore the role of clonidine in patients with TBI with suspected PSH., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Apixaban and rivaroxaban require lead-in dosing for 7 and 21 days, respectively, when treating venous thromboembolism (VTE). However, no evidence exists to support subtracting parenteral anticoagulation days from total lead-in dosing. A multicenter study was conducted, including adult patients with acute VTE who received apixaban or rivaroxaban. The patients were grouped as follows. The recommended group received oral lead-in anticoagulant for the full recommended duration. The mixed group received lead-in therapy as parenteral with oral anticoagulant. The incidence of recurrent VTE (rVTE) and major bleeding (MB) within 90 days were the main outcomes. Of the 368 included patients, 47.8% received apixaban, and 52.2% received rivaroxaban. The recommended lead-in was used in 296 patients (80.4%), whereas 72 (19.6%) received the mixed-lead-in regimen. Five patients had rVTE events within 90 days; two occurred during hospitalization in the recommended group versus none in the mixed group (0.7% vs. 0.0%; p = 1.000). After discharge, two events occurred in the recommended group and one in the mixed group (0.7% vs. 1.4%; p = 0.481). In terms of MB, 24 events occurred in 21 patients within 90 days. During hospitalization, 11 events occurred in the recommended group and seven in the mixed group (3.7% vs. 9.7%; p = 0.060). After discharge, five more events occurred in the recommended group and one in the mixed group (1.4% vs. 1.7%; p = 1.000). The mixed-lead-in regimen is safe and effective in comparison with the recommended-lead-in regimen.

Purpose: Coagulation abnormalities are one of the most important complications of severe COVID-19, which might lead to venous thromboembolism (VTE). Hypercoagulability with hyperfibrinogenemia causes large vessel thrombosis and major thromboembolic sequelae. Statins are potentially a potent adjuvant therapy in COVID-19 infection due to their pleiotropic effect. This study aims to evaluate the effectiveness of statins in reducing the risk of thrombosis among hospitalized critically ill patients with COVID-19., Methods: A multicenter, retrospective cohort study of all critically ill adult patients with confirmed COVID-19 admitted to Intensive Care Units (ICUs) between March 1, 2020, and March 31, 2021. Eligible patients were categorized based on their usage of statins throughout their ICU stay and were matched with a propensity score. The primary endpoint was the odds of all cases of thrombosis; other outcomes were considered secondary., Results: A total of 1039 patients were eligible; following propensity score matching, 396 patients were included (1:1 ratio). The odds of all thrombosis cases and VTE events did not differ significantly between the two groups (OR 0.84 (95% CI 0.43, 1.66), P  = 0.62 and OR 1.13 (95% CI 0.43, 2.98), P  = 0.81, respectively. On multivariable Cox proportional hazards regression analysis, patients who received statin therapy had lower 30-day (HR 0.72 (95 % CI 0.54, 0.97), P = 0.03) and in-hospital mortality (HR 0.67 (95 % CI 0.51, 0.89), P = 0.007). Other secondary outcomes were not statistically significant between the two groups except for D-dimer levels (peak) during ICU stay., Conclusion: The use of statin therapy during ICU stay was not associated with thrombosis reduction in critically ill patients with COVID-19; however, it has been associated with survival benefits.

Background: Vancomycin is a commonly used antibiotic in critically ill patients for various indications. Critical illness imposes pharmacokinetic-pharmacodynamics challenges, which makes optimizing vancomycin in this population cumbersome. Data are scarce on the clinical impact of time to therapeutic trough levels of vancomycin in critically ill patients.  This study aims to evaluate the timing to achieve therapeutic trough level of vancomycin on 30-day mortality in critically ill patients., Method: A retrospective cohort study was conducted for all adult critically ill patients with confirmed Gram-positive infection who received IV vancomycin between January 1, 2017, and December 31, 2020. We compared early (< 48 h) versus late (≥ 48 h) attainment of vancomycin therapeutic trough levels. The primary outcome was the 30-day mortality in critically ill patients. Secondary outcomes were the development of resistant organisms, microorganisms eradication within 4-5 days of vancomycin initiation, acute kidney injury (AKI), and length of stay (LOS). Propensity score-matched (1:1 ratio) used based on patient's age, serum creatinine, and albumin values at baseline., Results: A total of 326 patients were included; 110 patients attained the therapeutic trough levels within 48 h of vancomycin initiation. Late achievement of the therapeutic trough levels was associated with higher 30-day mortality (HR: 2.54; 95% CI [1.24-5.22]; p = 0.01). Additionally, patients who achieved therapeutic trough levels of vancomycin late were more likely to develop AKI (OR = 2.59; 95% CI [1.01-6.65]; p = 0.04). Other outcomes were not statistically significant between the two groups., Conclusion: Early achievement of vancomycin therapeutic levels in patients with confirmed Gram-positive infection was associated with possible survival benefits., (© 2021. The Author(s).)