ABSTRACT
Different dosage regimens of hydroxychloroquine (HCQ) have been used to manage COVID-19 (coronavirus disease 2019) patients, with no information on lung exposure in this population. The aim of our study was to evaluate HCQ concentrations in the lung epithelial lining fluid (ELF) in patients infected with SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), the virus that causes COVID-19. This was a retrospective, observational, multicentre, pharmacokinetic study of HCQ in critically ill COVID-19 patients. No additional interventions or additional samples compared with standard care of these patients were conducted in our teaching hospital. We included all intubated COVID-19 patients treated with crushed HCQ tablets, regardless of the dosage administered by nasogastric tube. Blood and bronchoalveolar lavage samples (n = 28) were collected from 22 COVID-19 patients and total HCQ concentrations in ELF were estimated. Median (interquartile range) HCQ plasma concentrations were 0.09 (0.06-0.14) mg/L and 0.07 (0.05-0.08) mg/L for 400 mg × 1/day and 200 mg × 3/day, respectively. Median HCQ ELF concentrations were 3.74 (1.10-7.26) mg/L and 1.81 (1.20-7.25) for 400 mg × 1/day and 200 mg × 3/day, respectively. The median ratio of ELF/plasma concentrations was 40.0 (7.3-162.7) and 21.2 (18.4-109.5) for 400 mg × 1/day and 200 mg × 3/day, respectively. ELF exposure is likely to be underestimated from HCQ concentrations in plasma. In clinical practice, low plasma concentrations should not induce an increase in drug dosage because lung exposure may already be high.
Subject(s)
Antiviral Agents/pharmacokinetics , COVID-19 Drug Treatment , Hydroxychloroquine/pharmacokinetics , Adult , Aged , Aged, 80 and over , Antiviral Agents/administration & dosage , Antiviral Agents/blood , Bronchoalveolar Lavage Fluid/chemistry , Critical Illness , Female , Humans , Hydroxychloroquine/administration & dosage , Hydroxychloroquine/blood , Intubation, Gastrointestinal , Lung/drug effects , Lung/virology , Male , Middle Aged , Retrospective Studies , Tablets/administration & dosage , Tablets/pharmacokineticsABSTRACT
BACKGROUND: The French legislature passed a law in 2005 that assigns a new role to the physician and redefines his liability in end-of-life decisions. METHOD: This law is presented and discussed in context with current French legal practice. RESULTS: This law emphasizes patient autonomy, advocating that the patient be fully informed before treatment, and creates specific procedures to be followed according to whether the patient is conscious or unconscious. In the latter situation, the law reinforces the role of both the patient's surrogate and the patient's advance directives in establishing consent. In these extreme situations, doctors have the option to request a second medical opinion. This joint decision-making procedure is laid down by law and becomes obligatory in the interests of transparency. CONCLUSION: Respect for patients' consent implies the possibility that they may refuse medical care, creating an ethical and legal dilemma of providing medical care or respecting the patients' wishes. The key issue concerning end-of-life patients rests in the decisions taken concerning the continuation or withdrawal of life support and the administration of palliative care.
