Basic Clin Pharmacol Toxicol
December 2023
Metabolomics in clinical toxicology aim at reliably identifying and semi-quantifying a broad array of endogenous and exogenous metabolites using dedicated analytical methods. Here, we developed a three-step-based workflow to investigate the metabolic impact of the antidepressant drug venlafaxine in a poisoned patient who developed life-threatening cardiac failure managed with extracorporeal membrane oxygenation. Both targeted quantitative and untargeted semi-quantitative metabolomic analyses using liquid chromatography hyphenated to high-resolution tandem mass spectrometry were performed to determine the plasma kinetics of venlafaxine, -desmethyl-venlafaxine, and -desmethyl-venlafaxine and to identify sixteen different venlafaxine-derived metabolites including one unknown (, venlafaxine conjugated to a hexosyl-radical), respectively.
View Article and Find Full Text PDFMethadone and buprenorphine are the two maintenance treatments in opiate addicts authorised in France since the end of the 1990's. More recently, some African countries such as Senegal have implemented a new health policy focused on reducing the risks by encouraging the use of methadone as maintenance treatment. The objectives of maintenance therapy are to reduce morbidity and mortality related to the consumption of heroin and other street opioids, to promote the integration of drug users into the healthcare system, and more generally, to improve their social integration.
View Article and Find Full Text PDFBasic Clin Pharmacol Toxicol
January 2023
Background: Tramadol-attributed toxicity may involve opioid-like, serotoninergic, and noradrenergic mechanisms. We investigated the mechanisms of toxicity in a massive tramadol ingestion case by examining serial clinical, imaging, electroencephalography, pharmacokinetics, and genotyping data.
Case Report: A 32-year-old female who presumably ingested 9000 mg sustained-release tramadol was found comatose without hypoglycemia, bradypnea, hypotension, marked hypoxemia or seizures.
Context: Since recovery or death is generally observed within a few days after intensive care unit (ICU) admission of self-poisoned patients in the developed countries, reasons for the prolonged ICU stay are of interest as they have been poorly investigated. We aimed to identify the characteristics, risk factors, outcome, and predictors of death in self-poisoned patients requiring prolonged ICU management.
Methods: We conducted an eight-year single-center cohort study including all self-poisoned patients who stayed at least seven days in the ICU.
Introduction: Coronavirus disease-2019 (COVID-19) may lead to acute respiratory distress syndrome requiring extracorporeal membrane oxygenation (ECMO). Patterns of inflammatory bronchoalveolar cells in COVID-19 patients treated with ECMO are not well described.
Objective: We aimed to describe inflammatory cell subpopulations in blood and bronchoalveolar lavages (BALs) obtained in critically ill COVID-19 patients shortly after ECMO implementation.
Medical imaging plays a major role in coronavirus disease-2019 (COVID-19) patient diagnosis and management. However, the radiation dose received from medical procedures by these patients has been poorly investigated. We aimed to estimate the cumulative effective dose (CED) related to medical exposure in COVID-19 patients admitted to the intensive care unit (ICU) in comparison to the usual critically ill patients.
View Article and Find Full Text PDFObjective: COVID-19 is associated with an increased prevalence of deep venous thrombosis (DVT), mainly in the lower limbs. However, the characteristics and rheological conditions, which contribute to facilitating DVT occurrence have been poorly investigated. We aimed to report DVT characteristics, vein diameters and peak blood flow velocities (PBFV) in the common femoral veins (CFVs) of critically ill COVID-19 patients.
View Article and Find Full Text PDFBackground: Valproic acid (VPA) poisoning is responsible for life-threatening neurological and metabolic impairments. Despite only low-level evidence of effectiveness, L-carnitine has been used for years to prevent or reverse VPA-related toxicity. We aimed to evaluate the effects of L-carnitine used to treat acute VPA poisoning on the time-course of plasma VPA concentrations and VPA-related toxicity.
View Article and Find Full Text PDFBackground: Direct oral anticoagulants (DOAC) are widely used due to favourable benefit/risk ratio. However, consequences of massive ingestion have been poorly investigated.
Objectives: We aimed to report outcome and pharmacokinetic parameters in patients who massively ingested DOACs.
(1) Background: Corticosteroids lower 28-day all-cause mortality in critically ill COVID-19 patients. However, the outcome of COVID-19 patients referred to the intensive care unit (ICU) for respiratory deterioration despite corticosteroids initiated during hospitalization before ICU admission has been poorly investigated. Our objective was to determine survival according to corticosteroid initiation setting.
View Article and Find Full Text PDFBackground: COVID-19 may lead to refractory hypoxemia requiring venovenous extracorporeal membrane oxygenation (ECMO). Survival rate if ECMO is implemented as rescue therapy after corticosteroid failure is unknown. We aimed to investigate if ECMO implemented after failure of the full-recommended 10-day corticosteroid course can improve outcome.
View Article and Find Full Text PDFBackground: The Intensive care unit (ICU) Requirement Score (IRS) has been defined as identifying poisoned patients on hospital admission who do not require ICU referral, in an effort to reduce health expenses. However, this score has been poorly validated. We aimed to evaluate the IRS in a large cohort of poisoned patients.
View Article and Find Full Text PDFCoronavirus disease 2019 (COVID-19) may be complicated by life-threatening pneumonia requiring tracheal intubation, mechanical ventilation and veno-venous extracorporeal membrane oxygenation (vvECMO). It is not yet clear to what extent and after which delay the most severe cases of COVID-19 pneumonia are reversible. Here, we present a 39-year-old patient who developed a severe COVID-19-attributed acute respiratory distress syndrome (ARDS) resulting in complete alveolar consolidation and airway closure for several weeks.
View Article and Find Full Text PDFBackground: Tramadol poisoning rarely causes serotonin toxicity, which mechanisms remain poorly understood. We investigated alterations in tramadol pharmacokinetics in a tramadol-poisoned patient who presented with marked and prolonged serotonin toxicity.
Case Report: A 21-year-old male self-ingested 750 mg-tramadol, 200 mg-sotalol, 400 mg-propranolol and 6 mg-lorazepam.
Background And Aims: Acetaminophen is a common cause of poisoning and liver injury worldwide; however, patient stratification is suboptimal. We aimed to assess the contribution of admission plasma procalcitonin concentration (PCT) to better identify acetaminophen-poisoned patients likely to develop liver injury.
Methods: We conducted a prospective observational cohort study including all acetaminophen-poisoned patients requiring N-acetylcysteine admitted in a toxicological intensive care unit between 2012 and 2017.
Warfare neurotoxicants such as sarin, soman or VX, are organophosphorus compounds which irreversibly inhibit cholinesterase. High-dose exposure with nerve agents (NA) is known to produce seizure activity and related brain damage, while less is known about the effects of acute sub-lethal dose exposure. The aim of this study was to characterize behavioral, brain activity and neuroinflammatory modifications at different time points after exposure to 4-nitrophenyl isopropyl methylphosphonate (NIMP), a sarin surrogate.
View Article and Find Full Text PDFAcute kidney injury (AKI) is the major complication of rhabdomyolysis. We aimed to identify the predictive factors for AKI and renal replacement therapy (RRT) requirement in poisoning-associated rhabdomyolysis. We conducted a cohort study including 273 successive poisoned patients (median age, 41 years) who developed rhabdomyolysis defined as creatine kinase (CK) >1000 IU/L.
View Article and Find Full Text PDFObjective: Coronavirus Disease-2019 (COVID-19) predisposes patients to thrombosis which underlying mechanisms are still incompletely understood. We sought to investigate the balance between procoagulant factors and natural coagulation inhibitors in the critically ill COVID-19 patient and to evaluate the usefulness of hemostasis parameters to identify patients at risk of venous thromboembolic event (VTE).
Patients And Methods: We conducted an observational study recording VTEs defined as deep vein thrombosis or pulmonary embolism using lower limb ultrasound (92% of the patients), computed tomography pulmonary angiography (6%) and both tests (2%).
Importance: Evidence regarding corticosteroid use for severe coronavirus disease 2019 (COVID-19) is limited.
Objective: To determine whether hydrocortisone improves outcome for patients with severe COVID-19.
Design, Setting, And Participants: An ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin.
Purpose: Early and reliable prognostication after cardiac arrest (CA) remains crucial. We hypothesized that protein-S100B (PS100B) could predict more accurately outcome in the early phase of CA compared with other current biomarkers.
Methods: This prospective single-center study included 330 adult comatose non-traumatic successfully resuscitated CA patients, treated with targeted temperature management but not extra-corporeal life support.