Effects of CYP2B6 Genetic Variants on the Propofol Dose and Response among Jordanian Arabic Patients Undergoing General Anesthesia.

BACKGROUND: Propofol is the most commonly used general anesthetic drug in many countries, including Jordan. However, there is a wide variation in the propofols' dose and response among the patients. Genetic variation in the cytochrome (CYP) 2B6 gene affects propofol metabolism and might affect propofol dose and response. AIMS: This study aimed to determine the influence of major genetic alleles of the CYP2B6 gene, CYP2B6*2A, *6A, *3, *4A, and *5A, on the required propofol dose and response among Jordanian Arabic patients attending The University of Jordan Hospital. METHODS: A total of 155 patients were administrated propofol. The propofol response was evaluated by monitoring the time to reach the bispectral index of 60 (BIS60) for every patient. The CYP2B6 genetic variants were genotyped by polymerase chain reaction followed by restriction through specific enzymes for CYP2B6 variants. RESULTS: It is found that patients with variant CYP2B6*2A and *4A alleles required significantly (P < 0.05) lower propofol doses, while patients with variant CYP2B6*6A, *3, and *5A alleles required higher propofol doses in comparison with patients carrying the wild CYP2B6 alleles. Patients with variant CYP2B6*2A and *3 alleles needed a significantly (P < 0.05) shorter while patients with variant CYP2B6*5A allele needed longer time of BIS60 than patients with wild CYP2B6*2A, *3, and *5A alleles. CONCLUSION: It is concluded that CYP2B6 genetic variants affect propofol dose and can explain, at least partly, the inter-individual variation in the propofol response. Further clinical studies with a larger sample size are needed to confirm the findings of this study.

Quantum Tunneling-Induced Membrane Depolarization Can Explain the Cellular Effects Mediated by Lithium: Mathematical Modeling and Hypothesis.

Lithium imposes several cellular effects allegedly through multiple physiological mechanisms. Membrane depolarization is a potential unifying concept of these mechanisms. Multiple inherent imperfections of classical electrophysiology limit its ability to fully explain the depolarizing effect of lithium ions; these include incapacity to explain the high resting permeability of lithium ions, the degree of depolarization with extracellular lithium concentration, depolarization at low therapeutic concentration, or the differences between the two lithium isotopes Li-6 and Li-7 in terms of depolarization. In this study, we implemented a mathematical model that explains the quantum tunneling of lithium ions through the closed gates of voltage-gated sodium channels as a conclusive approach that decodes the depolarizing action of lithium. Additionally, we compared our model to the classical model available and reported the differences. Our results showed that lithium can achieve high quantum membrane conductance at the resting state, which leads to significant depolarization. The quantum model infers that quantum membrane conductance of lithium ions emerges from quantum tunneling of lithium through the closed gates of sodium channels. It also differentiates between the two lithium isotopes (Li-6 and Li-7) in terms of depolarization compared with the previous classical model. Moreover, our study listed many examples of the cellular effects of lithium and membrane depolarization to show similarity and consistency with model predictions. In conclusion, the study suggests that lithium mediates its multiple cellular effects through membrane depolarization, and this can be comprehensively explained by the quantum tunneling model of lithium ions.

Preparedness of Frontline Doctors in Jordan Healthcare Facilities to COVID-19 Outbreak.

The number of COVID-19 (Coronavirus Disease of 2019) cases in Jordan is rising rapidly. A serious threat to the healthcare system appears on the horizon. Our study aims to evaluate preparedness of Jordanian frontline doctors to the worsening scenario. It has a questionnaire-based cross-sectional structure. The questionnaire was designed to evaluate preparedness according to knowledge about virus transmission and protective measures, adherence to protection guidelines, and psychological impacts affecting doctors. Institutional factors affecting doctors' readiness like adopting approach protocols and making protection equipment available were investigated; 308 doctors from different healthcare facilities participated (response rate: 53.9%). Approximately 25% of doctors (n = 77) previously took care of COVID-19 patients, and 173 (56.2%) have institutional COVID-19 approach protocols. Only 57 doctors (18.5%) reported all PPE (Personal Protective Equipment) available. The self-reported score of preparedness to deal with COVID-19 patients was 4.9 ± 2.4. Doctors having institutional protocols for dealing with COVID-19 cases and those with sustained availability of PPE reported higher scores of preparedness (5.5 ± 2.3 and 6.2 ± 2.1 with p < 0.001, respectively). Correlations with knowledge score, adherence to PPE score, and psychological impacts were investigated. The study revealed multiple challenges and insufficiencies that can affect frontline doctors' preparedness. Policy makers are urged to take these findings into consideration and to act promptly.

The effect of ondansetron administration 20 minutes prior to spinal anaesthesia on haemodynamic status in patients undergoing elective caesarean section: A comparison between two different doses.

BACKGROUND AND AIMS: Spinal anaesthesia is currently the most common method used for managing patients undergoing elective caesarean sections. Recent meta-analyses have been supporting the use of 5-HT3 antagonists, like ondansetron, to attenuate hypotension induced by spinal block. Various doses of ondansetron were given intravenously five minutes before spinal block. However, a consensus on definitive dose and timing for maximal benefit is yet to be agreed upon. METHODS: Our prospective randomised clinical trial investigated a new approach by administrating intravenous ondansetron 20 minutes before spinal anaesthesia. This work investigated ondansetron effect on both haemodynamic changes and vasopressors use by dividing patients into three groups. The first group O4 (n = 51) received 4 mg ondansetron, the second group O6 (n = 51) received 6 mg ondansetron, and the control group C (n = 50) received normal saline. We recorded systolic blood pressure (SBP), diastolic blood pressure (DBP) and the mean blood pressure (MBP) at different time intervals. RESULTS: There was no significant difference in blood pressure measurements among the study groups (P > 0.05). The consumption of ephedrine in the control group is higher than both of the ondansetron groups (P > 0.001), with a mean dose of 27.2 ± 20.5 mg of ephedrine for group C, compared to 17.8 ± 14.9 and 14.7 ± 11.3 in O4 and O6 groups, respectively. Episodes of hypotension and number of patients with hypotension were not significantly different among the studied groups (P = 0.07; P = 0.96, respectively). CONCLUSIONS: Prophylactic 4 and 6 mg ondansetron given 20 minutes before spinal anaesthesia in caesarean section does not reduce the incidence of hypotension.