Extracorporeal Membrane Oxygenation for Severe Acute Respiratory Distress Syndrome associated with COVID-19: An Emulated Target Trial Analysis.

RATIONALE: Whether COVID patients may benefit from extracorporeal membrane oxygenation (ECMO) compared with conventional invasive mechanical ventilation (IMV) remains unknown. OBJECTIVES: To estimate the effect of ECMO on 90-Day mortality vs IMV only Methods: Among 4,244 critically ill adult patients with COVID-19 included in a multicenter cohort study, we emulated a target trial comparing the treatment strategies of initiating ECMO vs. no ECMO within 7 days of IMV in patients with severe acute respiratory distress syndrome (PaO2/FiO2 <80 or PaCO2 ≥60 mmHg). We controlled for confounding using a multivariable Cox model based on predefined variables. MAIN RESULTS: 1,235 patients met the full eligibility criteria for the emulated trial, among whom 164 patients initiated ECMO. The ECMO strategy had a higher survival probability at Day-7 from the onset of eligibility criteria (87% vs 83%, risk difference: 4%, 95% CI 0;9%) which decreased during follow-up (survival at Day-90: 63% vs 65%, risk difference: -2%, 95% CI -10;5%). However, ECMO was associated with higher survival when performed in high-volume ECMO centers or in regions where a specific ECMO network organization was set up to handle high demand, and when initiated within the first 4 days of MV and in profoundly hypoxemic patients. CONCLUSIONS: In an emulated trial based on a nationwide COVID-19 cohort, we found differential survival over time of an ECMO compared with a no-ECMO strategy. However, ECMO was consistently associated with better outcomes when performed in high-volume centers and in regions with ECMO capacities specifically organized to handle high demand. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/)

The tramadol option

Tramadol is an option for the treatment of rheumatological pain. Its mode of action and safety profile distinguishes it from other opioids. Tramadol differs from other opioids by combining a weak opioid and a monoaminergic mode of action. It is effective in different types of moderate-to-severe pain, including neuropathic pain. Moreover, as the mode of action of tramadol does not overlap with that of NSAIDs, it is a useful agent to be combined with these drugs. Tramadol induces fewer opioid adverse reactions for a given level of analgesia compared with traditional opioids. Common adverse reactions of tramadol such as nausea and dizziness, which usually occur only at the beginning of therapy and attenuate over time, can be further minimized by up-titrating the drug over several days. Dose adjustment is only necessary in patients over 75 years of age, or in those with either hepatic or renal insufficiency. Tramadol should be avoided or used with caution in epileptics, or in individuals who are receiving seizure-threshold lowering drugs. Finally, tramadol has a low risk of abuse because it has only a weak opioid effect and its monoaminergic action could inhibit the development of dependence. The low abuse potential of tramadol has been demonstrated by postmarketing surveillance data

Sodium stibogluconate (pentostan) overdose in a patient with acquired immunodeficiency syndrome

A 32-year-old man with acquired immunodeficiency syndrome (AIDS) admitted to the hospital for treatment of visceral leishmaniasis was inadvertently given 10 times the prescribed first dose of sodium stibogluconate ([Sb] 6.5 g instead of 0.65 g). He experienced no immediate major toxicity during the first 48 hours, but a significant rise of pancreatic enzyme activities was observed (amylase at 10 times the upper limit of normal, lipase at 50 times the upper limit of normal) without clinical signs or indications on computed tomography (CT) of pancreatitis. The third day after the overdose, he developed appendicitis, which appeared coincidental; he recovered uneventfully from surgery. Most of the overdose of Sb was eliminated within the first few hours. Pharmacokinetics remained linear; the rapid, long elimination half-lives (2.7 hours and 54 hours, respectively) were similar to those in previously published results. The administration of a chelating agent, dimercaptosuccinic acid (DMSA), 72 hours after the Sb overdose did not modify the pharmacokinetics of the medication

Modulation cognitive et émotionnelle de la douleur: mécanismes de certaines approches cliniques révélés par les neurosciences

Cognitive and affective strategies are frequently used in clinical practice to modulate pain perception. They seem to rely on a descending neural system, which is able to inhibit the afferent nociceptive signal. Herein, we will review experiments on healthy volunteers, which explored the central mechanisms involved in the change in pain perception due to the modulation of attention, expectations or mood. A growing understanding of the cognitive and emotional modulation of pain perception has validated empirical practices in the acute pain context. This body of work, associated to the investigation of the dysfunction of this modualtion in chronic pain patients, could lead to developing new therapies, which would complement current treatments

In vitro forecasting of drugs that may interfere with codeine bioactivation

The O-demethylation of codeine (methylmorphine) into morphine is mediated by the polymorphic cytochrome P450 DB1 (P450 IID6). By means of in vitro screening in human liver microsomes we have studied the effect on codeine bioactivation of several drugs used as analgesics or as adjuvants for pain control. In microsomes from an extensive metabolizer subject, paracetamol (acetaminophen) and NSAIDs (acetylsalicylic acid, diclofenac, indomethacin, piroxicam, and pirprofen), benzodiazepines (chlordiazepoxide, clonazepam, diazepam, flunitrazepam, and midazolam), and anticonvulsants (carbamazepine and phenytoin) did not alter the reaction. There was marked inhibition of in vitro morphine production by neuroleptics (chlorpromazine, haloperidol, levomepromazine, and thioridazine), metoclopramide, and tricyclic antidepressants (amitriptyline, clomipramine, desipramine, imipramine, and nortriptyline). Enzyme kinetics showed competitive inhibition by neuroleptics (chlorpromazine Ki = 0.5 microM) and antidepressants (clomipramine Ki = 6.8 microM), which are substrates of the polymorphic monooxygenase. Due to the low affinity of codeine for P450 DB1 (Km = 100-200 microM), its bioactivation in extensive metabolizers, and thus its analgesic efficacy, is liable to vary greatly when it is combined with any drug that has a high affinity for the polymorphic isozyme

Sélection d'un médicament dans une classe thérapeutique donnée : l'exemple des «inhibiteurs de l'HMG-CoA réductase»

The HMG-CoA reductase inhibitors have similar therapeutic targets and indications. However, their potential pharmacokinetic drug-drug interaction profile may play a significant role in their safety profile in polymedicated and polymorbid patients and can serve as a selection criterion. If their utility is clearly demonstrated in selected conditions, their safety profile remains of concern. Beside dose-related hepatic and muscular injury, other rare and important adverse drug reactions have been reported after prolonged administration such as polyneuropathy, fibrotic interstitial pulmonary disease and lupus-like syndrome. Teratogenicity has also been associated with statin therapy

Prise en charge médicamenteuse de la douleur neuropathique : quelle place pour les traitements topiques?

Neuropathic pain is challenging to treat, partly because of the systemic side effects of the commonly used medications. Therefore topical analgesics are potentially very usefull. Lidocain, capsaicin, amitriptyline and ketamine have been used topically on a pathophysiological basis and because of their favourable safety profile. Application of lidocain 5%, capsaicin 0.025-0.075% and doxepin 3.3% is effective, although moderately in peripheric neuropathic pain with allodynia and should be considered as a therapeutic option. However, this option should be evaluated on an individual basis. The efficacy of topical amitriptyline and ketamine is not demonstrated

Lack of acetaminophen ceiling effect on R-III nociceptive flexion reflex

The analgesic efficacy of intravenous doses of acetaminophen (paracetamol) 0.5 g, 1 g and 2 g (administered as propacetamol) was assessed in 11 healthy subjects in a randomised, double-blind, placebo-controlled crossover study. The antinociceptive effect was assessed over 8 h by measurement of the nociceptive flexion reflex threshold (R-III) in response to selective transcutaneous electrical stimulations