Esketamine: Less Drowsiness, More Analgesia.

Racemic ketamine is a 1:1 mixture of 2 enantiomers that turn light in opposite direction: Dextrorotatory esketamine is approximately 4 times more affine for the N-methyl-D-aspartate (NMDA) receptor than levorotatory arketamine, which may explain why esketamine is about twice as potent as an analgesic and anesthetic as the racemate. Esketamine has attracted renewed interest in view of the opioid crisis, racemic ketamine's abuse, and esketamine's approval for expanded use. We evaluated the anesthesia literature concerning mental, cardiovascular, cerebral, and antinociceptive effects of esketamine published in English between 1980 and 2022. The review shows that esketamine and racemic ketamine are not "the same" at clinically equivalent analgesic and anesthetic dose: Psychomimetic effects seem to be essentially related to NMDA receptor blockade and esketamine is not devoid of unwanted mental impact. However, it probably involves less cholinergic inhibition. Cognitive disturbances during arousal, awakening, and recovery from the drug are less, and less pronounced with esketamine. The drug allows for an approximately 50% dose reduction in anesthesia and analgesia which goes along with a higher clearance and shorter recovery time as compared to racemic ketamine. In comparison of esketamine with placebo, esketamine shows cardiocirculatory stabilizing and neuroprotective effects which can be seen in anesthesia induction, cardiac surgery, and analgesia and sedation in brain injury. Evidence of esketamine's antinociceptive efficacy is inconsistent, although a recent meta-analysis reports improved pain relief after surgery in a study with short observation time. To better define esketamine's place, direct head-to-head comparison with the racemate at equi-analgesic/anesthetic dose is warranted.

Impact of SARS-CoV-2 pandemic on dermatology residents: A nationwide French study.

Background Coronavirus disease 2019 (COVID-19) has changed the practice of all health-care professionals. Determining the impact could prevent repercussions in future crisis. Objectives The objectives of the study were to assess the impact of the COVID-19 pandemic on dermatology residents' professional practice, working conditions, academic training and mental health. Methods An online questionnaire was sent to all French dermatology residents. We compared the activity of residents working in areas heavily impacted by COVID-19 to others. Logistic multivariate regressions were done, using as outcome variables the negative impact of the COVID crisis on residents' possibility to practice dermatology during the crisis, supervision, academic training and working more than 50 h/week. The last part of the questionnaire was the burnout questionnaire of Maslach. Results A total of 246 residents filled the questionnaire. Residents working in highly impacted COVID areas (odds ratio, OR 0.34 confidence interval, CI [0.18, 0.61], P ≤ 0.001), first-year postgraduate (PGY-1) residents (OR 0.46 CI [0.23, 0.91], P = 0.023) and those in private practice (OR 0.10 CI [0.01, 0.57], P = 0.032) were significantly less able to maintain dermatology activities. Worse supervision was significantly more frequent with non-PGY-1 residents (OR 3.24 CI [1.65, 6.65], P < 0.001). One hundred and eighty one residents claimed the pandemic to have a negative effect on their dermatology curriculum with no difference according to their regions' affection by COVID-19. This was mostly attributed to the cancelation of courses and congresses. PGY-1 residents (OR 2.09 CI [1.09, 4.04], P = 0.029) and residents in highly affected areas (OR 1.79 CI [1.01, 3.18], P = 0.049) were more at risk of working above the maximal legal working time. None of the residents was free of burnout symptoms. Conclusion Dermatology residents have been highly affected by COVID-19. It might be important to have a more integrated healthcare system to fight times of crisis with the least repercussions on residents.

Failure of a Mexican antivenom on recovery from snakebite-related coagulopathy in French Guiana.

INTRODUCTION: In French Guiana, most snakebites are caused by crotalids, with the main signs being tissue damage and bleeding due to venom-induced coagulopathy. Since December 2014 the Western Guiana Hospital (WGH) has used Antivipmyn Tri TM, a Mexican polyvalent antivenom. The aim of the study was to assess its benefit on the correction of snakebite-related coagulopathy. METHODS: This retrospective study included patients hospitalized at the WGH with snakebite and a coagulopathy defined by: a prothrombin rate (PR) lower than 45%, an activated partial thromboplastin time ratio (aPTTr) greater than 2 or a fibrinogen lower than 100 mg.dL-1. The antivenom group included patients receiving Antivipmyn Tri TM from December 2014 to September 2017. The control group included patients admitted between January 2013 and November 2014 (when antivenom was unavailable) or admitted between December 2014 and September 2017 during times of antivenom shortage. We graphically compared the time courses of PR, aPTTr and fibrinogen between groups. Other endpoints were the length of hospital stay and the need for surgery or dialysis. RESULTS: 84 patients were included: 42 in the antivenom group, 42 in the control group. Both groups were similar for age, sex-ratio, proportion of bleedings, necrosis, and severity. Most patients in the antivenom group received 3 vials. There were no significant differences in recovery of PR, aPTTr and fibrinogen through the first 24 h. Fibrinogen declined again in the control group at 30 h and showed a slower rise to normal concentration. There were no significant differences in any secondary endpoint. CONCLUSION: Antivipmyn Tri TM as currently used did not show any benefit in recovery from coagulopathy.

Thromboelastographic study of the snakebite-related coagulopathy in Djibouti.

: Hemostasis disorders are one of the major clinical conditions of snakebites and are because of mechanisms which may disrupt vessels, platelets, clotting factors and fibrinolysis. Thromboelastography (TEG) could help to understand these effects in the clinical practice. A retrospective study reports a series of patients presenting a snakebite-related coagulopathy, treated with antivenom and monitored with conventional tests and TEG in a French military treatment facility (Republic of Djibouti, East Africa) between August 2011 and September 2013. Conventional coagulation assays (platelets, prothrombin time, activated partial thromboplastin time, fibrinogen) and TEG measurements were taken on arrival and at various times during the first 72 h of hospitalization, at the discretion of the physician. The study included 14 patients (median age 28 years). Bleedings were present in five patients. All patients received antivenom. A coagulopathy was present in all patients and was detected by both conventional assays and TEG. None exhibited thrombocytopenia. Prothrombin time and fibrinogen remained abnormal for most of patients during the first 72 h. The TEG profiles of 11 patients (79%) showed incoagulability at admission (R-time > 60 min). TEG distinguished 10 patients with a generalized clotting factor deficiency and 4 patients with an isolated fibrinogen deficiency after an initial profile of incoagulability. Hyperfibrinolysis was evident for 12 patients (86%) after Hour 6. Snake envenomations in Djibouti involve a consumption coagulopathy in conjunction with delayed hyperfibrinolysis. TEG could improve medical management of the condition and assessment of additional therapeutics associated with the antivenom.

Cardiac arrest: should we consider norepinephrine instead of epinephrine?

A patient scheduled for a laparoscopic cholecystectomy had an anaphylactic shock during induction of anesthesia. After the injection of vecuronium, an unusual fall of arterial pressure occurred, with bradycardia, enlargement of the QRS complex, then a circulatory arrest. Chest compressions were initiated, while intravenous epinephrine 1 mg was administered. The cardiac rhythm turned into a ventricular fibrillation (VF). Despite continuous chest compressions with repeated boluses of epinephrine and several external electric shocks, the patient remained in VF. Because of obviously ß-adrenergic adverse effects, epinephrine was replaced with norepinephrine. Return of spontaneous circulation was observed, with the recovering of sinusal activity. After staying for several weeks in intensive care unit because of multiorgan failure, the patient recovered without sequelae. Blood samples and cutaneous testing confirmed an allergy to vecuronium. This case report of a cardiac anaphylaxis with prolonged cardiac arrest illustrates the dual activity and adverse effects of epinephrine. Although vasoconstriction is mandated during cardiopulmonary resuscitation to provide an acceptable perfusion pressure to organs, ß-adrenergic stimulation seems deleterious to the heart. Experimental studies have shown that blocking the ß-adrenergic effects of epinephrine attenuates postresuscitation myocardial dysfunction or helps the return of spontaneous circulation after VF. Norepinephrine, a potent α-adrenergic drug nearly devoid of ß-adrenergic properties, could be an interesting alternative to epinephrine. It can improve organ perfusion during cardiopulmonary resuscitation and could be more efficient than epinephrine in case of VF.