The relevance of magnesium homeostasis in COVID-19.

PURPOSE: In less than one and a half year, the COVID-19 pandemic has nearly brought to a collapse our health care and economic systems. The scientific research community has concentrated all possible efforts to understand the pathogenesis of this complex disease, and several groups have recently emphasized recommendations for nutritional support in COVID-19 patients. In this scoping review, we aim at encouraging a deeper appreciation of magnesium in clinical nutrition, in view of the vital role of magnesium and the numerous links between the pathophysiology of SARS-CoV-2 infection and magnesium-dependent functions. METHODS: By searching PubMed and Google Scholar from 1990 to date, we review existing evidence from experimental and clinical studies on the role of magnesium in chronic non-communicable diseases and infectious diseases, and we focus on recent reports of alterations of magnesium homeostasis in COVID-19 patients and their association with disease outcomes. Importantly, we conduct a census on ongoing clinical trials specifically dedicated to disclosing the role of magnesium in COVID-19. RESULTS: Despite many methodological limitations, existing data seem to corroborate an association between deranged magnesium homeostasis and COVID-19, and call for further and better studies to explore the prophylactic or therapeutic potential of magnesium supplementation. CONCLUSION: We propose to reconsider the relevance of magnesium, frequently overlooked in clinical practice. Therefore, magnesemia should be monitored and, in case of imbalanced magnesium homeostasis, an appropriate nutritional regimen or supplementation might contribute to protect against SARS-CoV-2 infection, reduce severity of COVID-19 symptoms and facilitate the recovery after the acute phase.

Recommendation on an updated standardization of serum magnesium reference ranges.

PURPOSE: Serum magnesium is the most frequently used laboratory test for evaluating clinical magnesium status. Hypomagnesemia (low magnesium status), which is associated with many chronic diseases, is diagnosed using the serum magnesium reference range. Currently, no international consensus for a magnesemia normal range exists. Two independent groups designated 0.85 mmol/L (2.07 mg/dL; 1.7 mEq/L) as the low cut-off point defining hypomagnesemia. MaGNet discussions revealed differences in serum magnesium reference ranges used by members' hospitals and laboratories, presenting an urgent need for standardization. METHODS: We gathered and compared serum magnesium reference range values from our institutions, hospitals, and colleagues worldwide. RESULTS: Serum magnesium levels designating "hypomagnesemia" differ widely. Of 43 collected values, only 2 met 0.85 mmol/L as the low cut-off point to define hypomagnesemia. The remainder had lower cut-off values, which may underestimate hypomagnesemia diagnosis in hospital, clinical, and research assessments. Current serum magnesium reference ranges stem from "normal" populations, which unknowingly include persons with chronic latent magnesium deficit (CLMD). Serum magnesium levels of patients with CLMD fall within widely used "normal" ranges, but their magnesium status is too low for long-term health. The lower serum magnesium reference (0.85 mmol/L) proposed specifically prevents the inclusion of patients with CLMD. CONCLUSIONS: Widely varying serum magnesium reference ranges render our use of this important medical tool imprecise, minimizing impacts of low magnesium status or hypomagnesemia as a marker of disease risk. To appropriately diagnose, increase awareness of, and manage magnesium status, it is critical to standardize lower reference values for serum magnesium at 0.85 mmol/L (2.07 mg/dL; 1.7 mEq/L).

Comparing Important and Well-documented Potential Drug-Drug Interactions between Emergency, Medical, and Surgical ICUs of a Respiratory Referral Center.

Introduction: Drug-drug interaction (DDI) is one of the major healthcare challenges in intensive care units (ICUs). The prevalence of DDIs and interacting drug pairs may vary between different types of ICUs. This study aimed to compare the frequency and nature of important and well-documented potential DDIs (pDDIs) in three types of ICUs. Materials and methods: A prospective study was conducted in medical (M), surgical (S), and emergency (E) ICUs of a tertiary referral center for respiratory diseases. A pharmacist checked the patients' files three days in a week for 6 months. The pDDIs were identified using the Lexi-Interact database. Interactions with a severity rating of D (modify regimen) and X (avoid combination) and with a reliability rating of good and excellent were considered important and well-documented. These pDDIs were evaluated in terms of drug combinations, mechanisms of interaction, and clinical management. Results: One hundred eighty-nine patients admitted to MICU, SICU, and EICU were included in the study. The percentage of patients who experienced at least one important and well-documented pDDI was 18.8% in MICU, 11.1% in SICU, and 11.8% in EICU. The most common drug pairs causing important and well-documented interactions were atracurium + hydrocortisone in MICU, meropenem + valproic acid in MICU and EICU, and aspirin + warfarin in SICU. Conclusion: The current study shows different frequency and nature of pDDIs between three types of ICUs. We recommend conducting similar studies in other settings to develop evidence-based guidance on clinically relevant pDDIs in different types of ICUs. How to cite this article: Hosseinpoor Z, Farzanegan B, Baniasadi S. Comparing Important and Well-documented Potential Drug-Drug Interactions between Emergency, Medical, and Surgical ICUs of a Respiratory Referral Center. Indian J Crit Care Med 2022;26(5):574-578.

An Observational Study of QTc Prolongation in Critically Ill Patients: Identification of Incidence and Predictors.

AIMS: Despite the importance of abnormal QTc interval values in intensive care unit (ICU) patients, there is a paucity of information on this topic. The current study was designed to identify the incidence and predictors of QTc prolongation in medical (M), surgical (S), and emergency (E) ICUs. MATERIALS AND METHODS: A prospective observational study was conducted for 6 months. Patients more than 18 years old who admitted to MICU, SICU, and EICU were included in the study. Electrocardiogram (ECG) was taken on day 1, 3, and 5 of ICU admission. The QTc intervals >460 ms in male and >470 ms in female and increased >60 ms above baseline were considered QTc prolongation. Comparative analysis was done between two groups of patients (normal vs prolonged QTc). Logistic regression models were carried out to determine the predictors of QTc prolongation. RESULTS: Incidence of QTc prolongation was 6.5, 9.8, and 15.7% on day 1, 3, and 5 of ICU admission, respectively. On day 1, the history of alcohol addiction and the reason of ICU admission were associated with a prolonged QTc. A significant association was demonstrated between administration of azithromycin and QTc prolongation on day 3. High serum creatinine and hospitalization in EICU were predictors of QTc prolongation on day 5 of ICU admission. CONCLUSION: The QTc prolongation is relatively common among patients admitted to ICUs and its incidence increases with increasing length of hospital stay. Predictors of QTc prolongation may be affected by the duration of ICU admission. Physicians should consider these predictors particularly before prescribing QTc-prolonging drugs. HOW TO CITE THIS ARTICLE: Farzanegan B, Hosseinpoor Z, Baniasadi S, Seyyedi SR, Rajabi M. An Observational Study of QTc Prolongation in Critically Ill Patients: Identification of Incidence and Predictors. Indian J Crit Care Med 2020;24(4):270-275.

Association of Cytochrome P450 2E1 and N-Acetyltransferase 2 Genotypes with Serum Isoniazid Level and Anti-Tuberculosis Drug-Induced Hepatotoxicity: A Cross-Sectional Study.

Background: Anti-tuberculosis drug-induced hepatotoxicity can result from genetic polymorphism of the isoniazid (INH) metabolizing enzyme. This study aimed to determine the effect of genetic polymorphism of N-acetyltransferase 2 (NAT2) and cytochrome P450 2E1 (CYP2E1) genes on serum isoniazid level and drug-induced hepatotoxicity. Methods: A cross-sectional study was conducted on 120 patients (with and without hepatotoxicity) with pulmonary tuberculosis from June 2019 to April 2022 in Tehran (Iran). High-performance liquid chromatography was used to measure the serum concentration of INH and acetylisoniazid (AcINH). NAT2 and CYP2E1 genotypes were determined using polymerase chain reaction and restriction fragment length polymorphism methods. Data were analyzed using SPSS software (version 22.0) with independent two-sample t test, Chi square test, or Fisher's exact test. P<0.05 was considered statistically significant. Results: A total of 40 patients showed hepatotoxicity. The risk of anti-tuberculosis drug-induced hepatotoxicity was significantly higher in patients who are slow acetylator (SA) phenotype than in rapid or intermediate acetylator (P<0.001). NAT2*4/*4 genotypes were not found in patients with hepatotoxicity. The frequency of NAT2*5 and NAT2*6 haplotypes and serum INH concentration was significantly higher in patients with hepatotoxicity than in those without (P=0.003, P<0.001, and P<0.001, respectively). NAT2*4 haplotype was correlated with protection against hepatotoxicity. A combination of SA and CYP2E1 C1/C1 genotype was significantly associated with hepatotoxicity (P<0.001). Conclusion: Hepatotoxicity in Iranian patients with tuberculosis was confirmed due to the presence of NAT2 SA polymorphism. Determining NAT2 and CYP2E1 genotypes and/or INH concentration can be a valuable tool to identify patients susceptible to hepatotoxicity.

Importance of Magnesium Status in COVID-19.

A large amount of published research points to the interesting concept (hypothesis) that magnesium (Mg) status may have relevance for the outcome of COVID-19 and that Mg could be protective during the COVID disease course. As an essential element, Mg plays basic biochemical, cellular, and physiological roles required for cardiovascular, immunological, respiratory, and neurological functions. Both low serum and dietary Mg have been associated with the severity of COVID-19 outcomes, including mortality; both are also associated with COVID-19 risk factors such as older age, obesity, type 2 diabetes, kidney disease, cardiovascular disease, hypertension, and asthma. In addition, populations with high rates of COVID-19 mortality and hospitalization tend to consume diets high in modern processed foods, which are generally low in Mg. In this review, we review the research to describe and consider the possible impact of Mg and Mg status on COVID-19 showing that (1) serum Mg between 2.19 and 2.26 mg/dL and dietary Mg intakes > 329 mg/day could be protective during the disease course and (2) inhaled Mg may improve oxygenation of hypoxic COVID-19 patients. In spite of such promise, oral Mg for COVID-19 has thus far been studied only in combination with other nutrients. Mg deficiency is involved in the occurrence and aggravation of neuropsychiatric complications of COVID-19, including memory loss, cognition, loss of taste and smell, ataxia, confusion, dizziness, and headache. Potential of zinc and/or Mg as useful for increasing drug therapy effectiveness or reducing adverse effect of anti-COVID-19 drugs is reviewed. Oral Mg trials of patients with COVID-19 are warranted.

Effectiveness of Short-term Use of Gabapentin as Pre-emptive Analgesia in Reducing Pain after Video Assisted Thoracoscopic Surgery.

Background: Pain control after thoracoscopy is one of the important issues in patient health care. Pre-emptive analgesia can reduce acute postoperative pain and also prevent chronic pain. This study aimed to evaluate the effectiveness of gabapentin (GABA analog) as pre-emptive analgesia in reducing pain and reducing opiate consumption after video-assisted thoracoscopic surgery (VATS) surgery. Materials and Methods: In this study, 67 patients undergoing thoracoscopic surgery were randomly divided into two groups (31 placeboes and 36 gabapentin). Patients received two capsules (300 mg gabapentin capsules or placebo) on the night before surgery and again one hour before surgery. After completion of the operation, all patients were transferred to the recovery. Evaluation of postoperative pain was performed using the visual analog scale (VAS) every 30 minutes and then after 2, 4, 6, 10, 24 hours. If patients had pain (VAS above 3), intravenous morphine was injected to relieve pain and the number of injections and the total dose of morphine administered was recorded. Results: There was no significant difference between the two groups regarding VAS, blood pressure (BP), heart rate (HR), respiratory rate (RR) and saturated oxygen level (SaO2), urea, creatinine, and adverse effects. Conclusion: Preoperative gabapentin administration did not affect postoperative pain reduction, but morphine consumption in the gabapentin group was decreased during the first 24 hours after VATS.

Antibiotic use Evaluation in Hospitalized Pediatric Patients with Respiratory Tract Infections: A Retrospective Chart Review Study.

INTRODUCTION: Respiratory tract infections (RTIs) are a common cause of antibiotic usage in hospitalized pediatric patients. Inappropriate use of antibiotics may lead to the emergence of multidrug-resistant microorganisms and increased treatment costs. OBJECTIVE: This study was designed to assess antibiotic usage in hospitalized pediatric patients with RTIs. METHODS: Medical charts of the patients admitted to the pediatric ward (PW) and pediatric intensive care unit (PICU) of a tertiary respiratory center were reviewed. Patients' demographic and clinical data, including gender, age, weight, history of allergy, length of hospital stay, clinical diagnosis, and prescribed antibiotics (indication, dose, and frequency of administration) were collected. The appropriateness of antibiotic usage was evaluated in each patient according to international guidelines. RESULTS: Two hundred seventy-nine hospitalized patients were included in the study. The most common reason for hospitalization was pneumonia (38%), followed by cystic fibrosis (20.1%) and bronchitis (5%). The most commonly used antimicrobial agents were ceftriaxone, azithromycin, and clindamycin which guideline adherence for their usage was 85.3%, 23.3%, and 47%; respectively. Inappropriate dose selection was the main reason for non-adherence to the guidelines. The adherence rate to RTIs' guidelines (considering all parameters for each patient) was 27.6%. Multivariate logistic regression analysis demonstrated CF and prescription of azithromycin are predictors of guideline non-adherence. CONCLUSION: We found relatively low adherence to international guidelines in our center that could be related to restricted definitions of optimal antibiotic therapy. Despite most patients received logical antimicrobial therapy, actions should be taken into account to reach optimal antibiotic usage.

Isoniazid blood levels in patients with pulmonary tuberculosis at a tuberculosis referral center.

BACKGROUND: Serum concentrations of isoniazid (INH) were evaluated in Iranian patients admitted to the Tuberculosis Ward of Masih Daneshvari Hospital, Tehran, Iran. Factors correlated to plasma INH levels were determined. METHODS: Blood samples were obtained 2 h after ingestion of 5 mg/kg INH in 82 patients (1 sample/patient) on days 3-15 of treatment. The following variables were investigated: INH plasma level, duration of therapy, age, sex, weight, dose of INH administered and smoking status. RESULTS: The average (±SD) age and weight of patients were 60.68 ± 18.53 years and 74.96 ± 7.15 kg, respectively. INH concentrations were low in 14.63% and high in 23.17% of the patients (INH reference range: 3-5 µg/ml). Plasma INH was statistically correlated with duration of INH administration (Kendall's rank correlation, r = 0.66, p < 0.001) but not with other variables. CONCLUSION: Based on the result of this study, plasma INH concentrations were not within the therapeutic range for 37.80% of the patients on conventional therapy. Therefore therapeutic drug monitoring may be needed to optimize INH dosage, especially in patients with inadequate clinical response or toxicity to INH.

Evaluation of the efficacy and safety of inhaled magnesium sulphate in combination with standard treatment in patients with moderate or severe COVID-19: A structured summary of a study protocol for a randomised controlled trial.

OBJECTIVES: Basic and clinical studies have shown that magnesium sulphate ameliorates lung injury and controls asthma attacks by anti-inflammatory and bronchodilatory effects. Both intravenous and inhaled magnesium sulphate have a clinical impact on acute severe asthma by inhibition of airway smooth muscle contraction. Besides, magnesium sulphate can dilate constricted pulmonary arteries and reduce pulmonary artery resistance. However, it may affect systemic arteries when administered intravenously. A large number of patients with covid-19 admitted to the hospital suffer from pulmonary involvement. COVID-19 can cause hypoxia due to the involvement of the respiratory airways and parenchyma along with circulatory impairment, which induce ventilation-perfusion mismatch. This condition may result in hypoxemia and low arterial blood oxygen pressure and saturation presented with some degree of dyspnoea and shortness of breath. Inhaled magnesium sulphate as a smooth muscle relaxant (natural calcium antagonist) can cause both bronchodilator and consequently vasodilator effects (via a direct effect on alveolar arterioles in well-ventilated areas) in the respiratory tract. We aim to investigate if inhaled magnesium sulphate as adjuvant therapy to standard treatment can reduce ventilation-perfusion mismatch in the respiratory tract and subsequently improve arterial oxygen saturation in hospitalized patients with COVID-19. TRIAL DESIGN: A multi-centre, open-label, randomised controlled trial (RCT) with two parallel arms design (1:1 ratio) PARTICIPANTS: Patients aged 18-80 years hospitalized at Masih Daneshvari Hospital and Shahid Dr. Labbafinejad hospital in Tehran and Shahid Sadoughi Hospital in Yazd will be included if they meet the inclusion criteria of the study. Inclusion criteria are defined as 1. Confirmed diagnosis of SARS-CoV-2 infection based on polymerase chain reaction (PCR) of nasopharyngeal secretions or clinical manifestations along with chest computed tomography (chest CT) scan 2. Presenting with moderate or severe COVID-19 lung involvement confirmed with chest CT scan and arterial oxygen saturation below 93% 3. Length of hospital stay ≤48 hours. Patients with underlying cardiovascular diseases including congestive heart failure, bradyarrhythmia, heart block, the myocardial injury will be excluded from the study. INTERVENTION AND COMPARATOR: Participants will be randomly divided into two arms. Patients in the intervention arm will be given both standard treatment for COVID-19 (according to the national guideline) and magnesium sulphate (5 cc of a 20% injectable vial or 2 cc of a 50% injectable vial will be diluted by 50 cc distilled water and nebulized via a mask) every eight hours for five days. Patients in the control (comparator) arm will only receive standard treatment for COVID-19. MAIN OUTCOMES: Improvement of respiratory function and symptoms including arterial blood oxygen saturation, dyspnoea (according to NYHA functional classification), and cough within the first five days of randomization. RANDOMISATION: Block randomisation will be used to allocate eligible patients to the study arms (in a 1:1 ratio). Computer software will be applied to randomly select the blocks. BLINDING (MASKING): The study is an open-label RCT without blinding. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): The trial will be performed on 100 patients who will be randomly divided into two arms of control (50) and intervention (50). TRIAL STATUS: The protocol is Version 5.0, January 05, 2021. Recruitment of the participants started on July 30, 2020, and it is anticipated to be completed by February 28, 2021. TRIAL REGISTRATION: The trial was registered in the Iranian Registry of Clinical Trials (IRCT) on July 28, 2020. It is available on https://en.irct.ir/trial/49879 . The registration number is IRCT20191211045691N1. FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest of expediting the dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.

Metabolism-based Drug-drug Interactions in Patients with Chronic Respiratory Diseases: A Review Focusing on Drugs Affecting the Respiratory System.

BACKGROUND: Chronic respiratory diseases (CRDs) are increasing in prevalence, as reported by the World Health Organization (WHO). Patients with CRDs usually require co-administration of multiple drugs due to the complex pathogenic mechanisms of CRDs and the existence of concomitant diseases. Polypharmacy (co-administration of more than four medications) is the main risk factor of the occurrence of drug-drug interactions (DDIs) that may lead to reducing treatment efficacy and/or increasing adverse effects. METHODS: This literature-based review focuses on metabolism-based DDIs, the most prevalent DDIs responsible for difficulties in therapeutic management in patients with CRDs. RESULTS: Clinically relevant metabolism-based DDIs occur between drugs used for the treatment of respiratory diseases (corticosteroids, orally inhaled bronchodilators, methylxanthines, anti-leukotrienes, antimicrobials, endothelin receptor antagonists, phosphodiesterase inhibitors, antitussives, and antineoplastic agents) and drugs affecting cytochrome P450 (CYP) (inducers and inhibitors). Considering alternative therapies, adjusting medication doses, or monitoring patients during treatment are recommended to prevent the harmful consequences of these interactions. CONCLUSION: Providing information on clinically relevant interactions of drugs more likely prescribed in daily practices of physicians is essential to improve patient safety. A list of known metabolism-based interactions of drugs affecting the respiratory systems should be available for physicians engaged in the treatment of CRDs.

Clinically important drug-drug interactions in patients admitted to hospital with COVID-19: drug pairs, risk factors, and management.

OBJECTIVES: Coronavirus disease 2019 (COVID-19) is an emerging viral infection without any approved treatment. Investigational therapies for COVID-19 may cause clinically important drug-drug interactions (DDIs). We aimed to study potential DDIs (pDDIs) and their risk factors in COVID-19 patients admitted to the hospital. METHODS: We conducted a cross-sectional study in a tertiary respiratory hospital dedicated to COVID-19 patients. The Lexi-Interact database was used to investigate clinically important pDDIs. The database output including interacting drug pairs, risk rating, reliability rating, mechanism, and management was evaluated. Associations between the occurrence of pDDIs and probable risk factors were assessed by logistic regression analysis. RESULTS: Medical charts of 227 patients were reviewed. About 38% of the patients had at least one clinically important pDDI. More than half of the interactions were between protease inhibitors (lopinavir/ritonavir) and regularly prescribed medications for the management of comorbidities or COVID-19 symptoms (e.g., atorvastatin, alprazolam, salmeterol, and tamsulosin). Ischemic heart disease, chronic respiratory diseases, and ICU admission were significantly associated with the occurrence of pDDIs. CONCLUSIONS: We recommend considering the risk factors for the emergence of clinically important DDIs in the pharmacotherapy of COVID-19 patients. Using an alternative medication or dose adjustments may be required in high-risk patients.

Potential drug-drug interactions in hospitalized pediatric patients with respiratory disorders: a retrospective review of clinically important interactions.

Background Hospitalized pediatric patients are at an increased risk of experiencing potential drug-drug interactions (pDDIs) due to polypharmacy and the unlicensed and off-label administration of drugs. The aim of this study is to characterize clinically significant pDDIs in pediatric patients hospitalized in a tertiary respiratory center. Methods A retrospective analysis of medications prescribed to pediatric patients admitted to the pediatric ward (PW) and pediatric intensive care unit (PICU) of a respiratory referral center was carried out over a six-month period. The pDDIs were identified using the Lexi-Interact database and considered as clinically relevant according to the severity rating as defined in the database. Frequency, drug classes, mechanisms, clinical managements, and risk factors were recorded for these potential interactions. Results Eight hundred and forty-five pDDIs were identified from the analysis of 176 prescriptions. Of the total pDDIs, 10.2% in PW and 14.6% in PICU were classified as clinically significant. Anti-infective agents and central nervous system drugs were the main drug classes involved in clinically significant pDDIs as object and/or precipitant drugs. A higher number of medications [odds ratio (OR): 4.8; 95% confidence interval (CI): 2.0-11.4; p < 0.001] and the existence of a nonrespiratory disease, which led to a respiratory disorder (OR: 3.8; 95% CI: 1.40-10.4; p < 0.05), were the main risk factors associated with an increased incidence of pDDIs. Conclusions A high and similar risk of pDDIs exists in pediatric patients with respiratory disorders hospitalized in PW and PICU. The patients prescribed a higher number of medications and presenting respiratory symptoms induced by a nonrespiratory disease require extra care and monitoring. Pediatricians should be educated about clinically significant DDIs for highly prescribed medications in their settings in order to take preventive measures and safeguard patient safety.

Transcription errors observed in a teaching hospital.

Medication errors are among the most common medical errors in the hospitals. Transcription error is a specific type of medication errors and is due to data entry error that is commonly made by the human operators. This study was designed to detect transcription errors in a teaching hospital in Tehran. Direct observational method was used in this study. Error was defined as any deviation in transcribing medication order from the previous step (order on the order sheet, administration nursing note and/or cardex, documentation of the order in the pharmacy database). A total of 287 charts with 558 opportunities for error were reviewed. Of those opportunities for error 167 (29.9%) resulted in an error. Omission (the patient did not receive the medication that was ordered) was the highest (52%) transcription error type seen in this study. The evaluation clearly showed that errors at transcription stage were not infrequent. To cut these errors down we suggest implementation of surveillance systems, which might help to decrease medication errors.

Effect of Nebulized Verapamil on Oxygenation in Chronic Obstructive Pulmonary Disease (COPD) Patients Admitted to the Intensive Care Unit.

BACKGROUND: Many pharmacological and behavioral therapies have been investigated to improve oxygenation in the intensive care unit (ICU). In patients with chronic obstructive pulmonary disease (COPD), the purpose of therapy is to correct the ventilation perfusion (V/Q) mismatch. Agents, such as calcium blockers, can affect both ventilation and vasculature. The inhalation route allows a more rapid achievement of therapeutic effects with few systemic side effects. Therefore, the present study aimed to investigate the effect of nebulized verapamil on oxygenation in COPD patients. MATERIALS AND METHODS: In this double-blind, randomized clinical trial, twenty hypoxic COPD patients, admitted to ICU, were treated with 10 mg of verapamil twice daily for three days. Also, twenty patients with COPD, who were matched in terms of age, sex, and severity of the disease, were enrolled in the control group and received nebulized normal saline. The oxygenation parameters were compared using an arterial blood gas (ABG) test before and after the intervention. RESULTS: The mean oxygen saturation was 91.2%±12.15 before verapamil inhalation, which increased to 95.75%±14.57 after receiving nebulized verapamil (P<0.05). Also, correction of blood pH, blood oxygen pressure, and oxygen ratio (PaO2/FIO2) were higher in patients receiving verapamil, compared to the control group. The length of hospital stay was similar in the two groups. During the first three days, 30% of patients in the verapamil group and 20% of patients in the control group were intubated. CONCLUSION: Our results indicated that verapamil inhalation increased oxygen saturation and accelerated extubation in patients with COPD.

Drug interactions and creatinine levels are associated with QTc prolongation in intensive care units: a prospective, observational study.

Background Prolongation of the QTc interval may lead to life threatening arrhythmias. QTc prolongation is common in intensive care unit (ICU) patients. The objectives of this study were to identify the role of drug-drug interactions (DDIs) and other predictors (age, sex, cardiovascular diseases, and electrolyte abnormalities) in life threatening QTc prolongation in patients admitted to medical (M), surgical (S) and emergency (E) ICUs. Methods This prospective, observational study included patients above the age of 18 years who were admitted to SICU, EICU, and MICU at a tertiary respiratory referral center. Electrocardiogram (ECG) monitoring was performed during the first 5 days of ICU admission. Risk factors and DDIs which were anticipated to be associated with the prolongation of the QTc interval were assessed for all patients. Results Two hundred patients were included in the study. QTc prolongation occurred in 10.7% of patients and the majority of patients presenting with QTc prolongation had creatinine levels above 1.3 mg/dL during their 5 days of ICU admission. Incidence of pharmacodynamic (PD) DDIs was significantly higher in patients with QTc prolongation vs. other patients. Creatinine levels above 1.3 mg/dL and PD DDIs were associated with QTc prolongation during 5 days of ICU admission. Conclusions High serum creatinine and PD DDIs can increase the risk of QTc prolongation in patients admitted to the ICU. QTc interval measurements should be performed prior to initiation or after starting any drug that is associated with QT prolongation, specifically in patients with the known risk factors.

Important exposure controls for protection against antineoplastic agents: Highlights for oncology health care workers.

BACKGROUND: A great number of antineoplastic drugs (ANPDs) are used globally in cancer treatment. Due to their adverse health effects, occupational exposure to ANPDs is considered a potential health risk to health care workers. OBJECTIVE: The current study aimed to evaluate safe-handling practices of ANPDs, exposure controls, and adverse health implications for health care providers exposed to ANDPs. METHODS: Prevention measures, including engineering, administrative, and work practice controls, as well as personal protective equipment (PPE), were recorded daily through a questionnaire for six weeks. Acute adverse health effects experienced by health care workers were also documented. RESULTS: The implemented exposure controls for preparation, administration, cleaning, and waste disposal were not in accordance with the safe handling guidelines. Central nervous system disorders (26.33%) were the most frequent acute adverse effects reported by health care workers. A significant correlation was found between the number of experienced adverse effects and handling characteristics, including the number of preparations (r = 0.38, p < 0.05), dose, and the number of prepared drugs (r = 0.46, p < 0.01 and 0.39, p < 0.05), and working hours in different locations of oncology setting for six weeks (preparation room: r = 0.38, P < 0.05, treatment room: r = 0.46, P < 0.01, patient room: r = 0.63, P < 0.01, and station: r = 0.68, P < 0.01). CONCLUSIONS: Due to inadequate control measures, oncology health care workers were in danger of exposure to ANPDs and experienced acute adverse health effects. Implementation of appropriate exposure controls is required to prevent occupational exposure to ANPDs.

Potential Drug-Drug Interactions Among Critically Ill Pediatric Patients in a Tertiary Pulmonary Center.

Patients in the pediatric intensive care unit (PICU) are at increased risk of potential drug-drug interactions (pDDIs) because of the complexity of pharmacotherapy. The current study aimed to assess the rate, pattern, risk factors, and management of pDDIs in the PICU of an academic pulmonary hospital. A prospective observational study was conducted for 6 months. Pharmacotherapy data of PICU-admitted patients were evaluated by a clinical pharmacologist. Interacting drugs, reliability, mechanism, potential outcome, and clinical management of pDDIs were identified using the Lexi-Interact database. Logistic regression was applied to analyze the risk factors that could be associated with the interactions. One hundred and twenty-three medication profiles were evaluated during the study period. Diseases of the respiratory system were the main diagnoses among intensive care unit (ICU)-admitted patients (56.1%). A total of 38.6% of the patients exposed to at least 1 major and/or contraindicated interaction during ICU admission. Most pDDIs occurred through metabolic (35.4%) and additive (34.8%) mechanisms. The existence of pDDIs was significantly associated with the number of prescribed medications. Exposure to pDDIs is frequent in critically ill pediatric patients and related to the number of medications. Daily and close cooperation between clinicians and clinical pharmacologists is recommended to prevent harmful outcomes of DDIs.

Biological Monitoring of Healthcare Workers Exposed to Antineoplastic Drugs: Urinary Assessment of Cyclophosphamide and Ifosfamide.

Exposure of health care workers to antineoplastic drugs and subsequent adverse health effects is still an open issue. Very little has been studied on the extent of occupational exposure and handling conditions of antineoplastic drugs in Iran. We aimed to determine cyclophosphamide and ifosfamide concentrations in the urine samples of oncology healthcare workers. In addition, we assessed workplace safety controls that are important to decrease occupational exposure. Urinary samples of subject and control groups were collected to measure pre and post-shift cyclophosphamide and ifosfamide concentrations. Prior to sample collection, an occupational toxicologist observed and recorded working safety conditions for the healthcare workers during an eight-week period. Heath care workers were also asked about occurrence of acute adverse health effects. A total number of 425 chemotherapeutic drugs (389.83 g) were prepared during the study. Cyclophosphamide was detected in five pre-shift and nine post-shift urine samples. One pre-shift and four post-shift urine samples were positive for Ifosfamide. The urine samples of control group had no detectable concentrations of cyclophosphamide and ifosfamide. Personal protective equipment usage was not adequate for handling activities. Some adverse health effects reported by oncology personnel confirmed exposure to antineoplastic drugs. High percentage of oncology personnel was exposed to antineoplastic drugs that could be related to the large amount of drug preparations and inadequate safety controls. We recommend training of oncology personnel, implementation of safety controls, and periodic surveillance in order to minimize workplace contamination and occupational exposure to antineoplastic drugs.