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.

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.

Anesthesia & Analgesia: June 2021 - Volume 132 - Issue 6 - p e114-e116 doi: 10.1213/ANE.0000000000005507

Background and objectives: We measured the impact of the COVID-19 pandemic on the mental health and burnout of French residents. Methods: Residents completed a questionnaire assessing their personal life, work, social relationships, mental health, burden and psychological impact of the pandemic. The Maslach Burnout Inventory (MBI) allowed to identify 5 classes of burnout of increasing severity: burnout free, intermediate, 1, 2 or 3 dimensions severely impacted. Variables significantly linked with burnout, defined as having a high impact on at least one of the 3 dimensions of the MBI, were entered into a logistic regression. Results: There were 1050 responses. Mean age was 27 +/- 2 years. Since the start of the pandemic, only one resident in four said they were in their normal state of mind, more than half felt tired and one third anxious and/or stressed and/or depressed. The total burnout rate was 55%. There was a strong link between the severity of the burnout syndrome and the impact of the pandemic. 7 factors were independently linked to burnout: number of monthly calls (p < 0.001), psychiatric history (p < 0.001), interpersonal conflicts (p = 0.002), desire to quit the specialty (p = 0.002), fatigue (p = 0.004), job satisfaction (p = 0.004), and depression (p = 0.05). Conclusion: Caring for Covid positive patients was not the most important cause of burnout, but there was a strong relationship between burnout severity and psychological impact of the pandemic. (C) 2021 Asociacion Universitaria de Zaragoza para el Progreso de la Psiquiatria y la Salud Mental. Published by Elsevier Espana, S.L.U. All rights reserved.

To the Editor The recent publication by Highland et al1 is particularly interesting, and we were impressed by the sophisticated statistical analysis, based on a propensity score matching for control of confounding factors. We thank the authors for citing our French study in Afghanistan (2010–2012), and we give further details.2 Highland et al1 observed that ketamine administered in 107 military combat casualties was not associated with the subsequent development of posttraumatic stress disorder (PTSD) when compared with 1051 cases of those who did not receive ketamine. As in our study, this study revealed that soldiers given ketamine tended to be more severely injured than those who did not. The authors acknowledged that one limitation of their study was that no records existed about the possible administration of ketamine in theater, and that they assumed that ketamine administration in theater was equally represented across the ketamine and matched nonketamine patients in their study. Although our study was also retrospective, one of its strengths was that times of ketamine administration were precisely known from medical records filed during battlefield care and from databases from medical evacuations. A total of 274 soldiers were included in the analysis. Among these, 98 (36%) experienced PTSD, and 89 (32%) received ketamine. The diagnosis of PTSD was made by a psychiatrist between 3 and 6 months after return from a war mission and confined to a 2-year observation period. In the logistic regression model, like in the Highland et al1 study, administration of ketamine was not independently related to the occurrence of either acute stress disorder (ASD) or subsequent PTSD development. At multivariable analysis, only ASD and the total number of surgical procedures were independently associated with the development of PTSD. Medical practitioners in the French Military Health Service commonly administer ketamine to injured patients for care at the battlefield, during surgical procedures, and for postoperative analgesia. Ketamine was administered in the prehospital setting (battlefield) 41 times, and in the field hospital 70 times. Moreover, the doses of ketamine administered both on the battlefield and at the field hospital were recorded in 50 patients. There was no statistically significant difference between the mean (standard deviation [SD]) doses of ketamine administered to the 32 patients in the PTSD group and the 18 patients in the no PTSD group: 173 (144) mg vs 209 (152) mg, respectively. Georges Mion, MDAnaesthesia DepartmentCochin HospitalParis, France[email protected]Jean Le Masson, MDGeneral Medicine DepartmentFrench Navy Medical ServiceBrest, FranceClaire Granier, MDPsychiatry DepartmentPaul Guiraud HospitalVillejuif, FranceClément Hoffmann, MDBurn CenterPercy Military Teaching HospitalClamart, France

Dear Editor, We thank Drs Greene and Brandehoff for their interest in our article, but we are surprised that they consider a study comparing the kinetics of hemostasis in 84 patients envenomed main...

To editor: Snakebite envenomation (SBE) is a life-threatening disease that typically results from the injection of toxins following the bite of a venomous snake. It affects people in predominantly poor, rural communities in tropical and subtropical countries. About 50%–55% of all snakebites result in envenoming.1 Snakebite is a common neglected public health issue. In Burkina Faso, the snake species belong to six families, among which Elapidae and Viperidae are the most venomous. A retrospective study showed that the total number of snakebite cases recorded from 2010 to 2014 was 114 126 with an average annual incidence of (136 ± 9) bites per 100 000 people.2 With over 20 000 snake bites, of which nearly 15 000 envenomations, treated in health facilities about 300 deaths reported every year. Woman is more frailty to envenomation with high risk of complication than other group of population. Snake bite induced coagulopathy is the most life-threatening complication with poor maternal and perinatal outcome.3 Literature to guide management of this rare obstetric complication remains limited. We report a case of a 3 gravida of 36 weeks of gestation with snakebite who was succesfully managed. Written consent for the use of case presentation and figures, and consent for publication in print and electronically has been given by the patient. Case presentation A 21 years old patient, gravida 3, para 2 was bitten by a snake at around 4 PM while she was looking for wood in the vicinity of her house. She experienced severe pain on the outside of her left foot. After calling for help, she tried unsuccessfully to kill the snake that fled into the bundles. Ten minutes after the bite, she felt palpitations, dizziness, and nausea and in 30 minutes the family drove her on a moped to the near health facility located 15 km from their residence. During the travel, women suffered an abrasion by the motorcycle's rays from the toes of the bitten foot. She was admitted to the health center at 6 PM (2 hours after the bite) and the clinical examination revealed prostration, blood pressure at 100/60 mm Hg, apyrexia, fetal heart sounds present, but gums bleeding and bleeding at the bite points. She received isotonic saline, 4 mg dexamethasone per os, 1 g amoxicillin per os and was evacuated the referral hospital at 6:55 PM. She was admitted to medical emergencies at 3 hours after bite and the clinical signs were blood pressure at 90/60 mm Hg, chest pain, agitation, multiple bleeding (bite marks, puncture marks, bleeding of gums, traumatic wounds). After a compression dressing of the lesions and administration of 1 g of paracetamol, the patient was transferred to the maternity ward at 7:50 PM for vomiting and severe pain. She then received 500 mL of gelatin, 500 mL of Ringer lactate, 2 g of ceftriaxone, 1 g of paracetamol. At 8:45 PM the intensive care physician observed drowsiness, Glasgow coma scale of 10, and shock (pulse at 134 bpm, and blood pressure at 90/60 mm Hg). Multiple of bleeding with significant edema of the left lower limb, extending to the root of the thigh (Figs. 1–3). The dry tube coagulation test showed an absence of thrombus after 20 minutes. Laboratory tests showed hemoglobin was 112 g/L, hyperleukocytosis was 17 × 109/L, and platelet count was 490 × 109/L, creatinemia was 84 μmol/L; hypoglycemia was 3.2 mmol/L. Fetal activity was detected with heart rate of 148 bpm.Figure 1: Bleeding and edema of the left lower limb (regional hospital).Figure 2: Gums bleeding (regional hospital).Figure 3: Edema of the left lower limb (intensive care unit).The treatment were intravenous infusion of 1 500 mL of saline and 500 mL of gelatine, 10 mg of intravenous vitamin K. One dose of anti-venom diluted in 500 mL of glucose serum was given. Management has been completed by a second peripheral venous access, nasal oxygen therapy, 4 mg ondansetron, 1 g tranexamic acid by intravenous injection followed by 1 g tranexamic acid infused every 8 hours, ceftriaxone 2 g. A permanent urinary catheter was placed. The fresh plasma requested was not available in this hospital. After 30 minutes of resuscitation, a spectacular clinical situation was observed: sudden awakening on call, followed by an unmotivated smile, a sitting position with consistent verbal communication. Glasgow scale 15 points with blood pressure 110/60 mm Hg; stop vomiting, stop bleeding, change functional signs. The coagulation test done had come-back negative. Despite the favorable evolution, an evacuation to Ouagadougou was taken due to the unavailability of fresh frozen plasma (FFP). After 2 hours of driving in a nonmedical ambulance under 4 L/min oxygen, she was admitted to intensive care and with Glasgow 15 scale; stopped bleeding, clinical anemia, severe edema of the left lower limb, tense, shiny, and painless. Biology reports a prothrombin time 89%, a hemoglobin level of 100 g/L, platelet count 168 × 109/L, leukocytes 13 × 109/L, a normal blood ionogram, creatinemia, normal alanine aminotransferase and aspartate aminotransferase and normal fibrinemia, the Table 1 give reports of clinical examinations and laboratory tests. A second dose of antivenom was given; Exacyl 1 g then 6 g/24 hours, paracetamol 1 g infusion every hour. An initiated FFP transfusion was interrupted due to a transfusion-related event (generalized edema with vertigo, nausea, pruritus) treated with hydrocortisone 100 mg with oxygen.Table 1: Reports of clinical examinations and laboratory tests.An obstetrical ultrasound showed a progressive pregnancy of 36 weeks with a heart rate at 178 bpm. Biology showed anemia at 90 g/L, platelets at 164 × 109/L and a prothrombin level at 100%. The woman is transferred to obstetric ward where she received a transfusion of 2 units of red blood cell on 2017.09.02 for anemia at 70 g/L. Spontaneous labor occurred with the vaginal delivery (7 days after envenomation) of a female newborn baby Apgar 7-9-10 and birth weight 2 500 g (Fig. 4). The newborn was seen by a pediatrician and the woman was discharged from hospital 10 days after envenimation. At the follow-up consultation at 14 days postpartum the mother and baby exam were normal.Figure 4: Patient with her child in obstetric ward.Discussion SBE is not a common during pregnancy but the obstetrical consequences are severe and related to severity of envenomation. Studies reporting SBE are rare in developed countries while present in developing countries.4 In Burkina Faso, snakebites are among the five leading causes of consultations in health districts.2 The notification of snakebites is operational in Burkina Faso since 2010, which helped in clarifying and mapping their incidence and mortality. The snake bite took place near the woman's family during the wintering period. This is a period with a high risk of poisoning with weeding, cutting down shrubs and humidity. Several authors have reported cases of envenimation occurring mainly during the wintering period.2,5 In this case, haemorrhage is observed in the lower third of the leg and most studies have described a similar result.6 Complications observed were shock, hemorrhage, digestive and neurological disorders. These signs are described differently depending on the series of cases reported.4,6,7 Management consisted of hydroelectrolytic equilibration and hematologic resuscitation and the use of polyvalent anti-venom. This management does not differ from the recommendations.5,8 A transfusion of FFP resulted in an urticaria-like reaction that was successfully managed with corticosteroids. The mother-fetal prognosis was good in this case with the birth of a healthy newborn. The rapidity of care and the use of the anti-venom saved the mother and her child. Snake bite when it occurs; is associated with fetal and maternal complications depending on the degree of envenomation5 and time to have care. Langley in his review of literature on snakebite in pregnancy reported maternal case-fatality of 4.2% and fetal death rate in the range of 43%–58% when there is envenomation. The maternal and obstetric complications observed were obstetric hemorrhage, preterm labour and delivery, disseminated intravascular coagulation, hypotension, hypovolemic shock, and anemia; while fetal and neonatal complications included tachycardia, prematurity, neonatal jaundice, anemia, and sepsis according to literature.5,9 Maternal and fetal survival with late presentation and systemic envenomation in low resource setting is uncommon, and this probably because snake venom was slow-acting, the amount of venom injected was small or the bite site location limited rapid absorption of snake venom. A combination of several factors may have played out.10 In developing countries where blood products are not readily available, when transfusion with clotting factors are required; fresh whole blood is transfused alternatively especially in patients with or at risk of anemia. In most rural areas in developing countries where there are no hematologists, clinicians rely on 20-minute whole blood clotting test; a simple and rapid test of blood coagulability which can be done by the bedside and has been found to correlate well with fibrinogen concentration. Anti-snake venoms (ASV) are scarce, expensive.5,7,11 Its use in pregnancy should therefore be with caution and only when there is threat to life as seen in this patient with local and systemic envenomation. Scarcity of ASV in rural areas of developing countries results in high morbidity and mortality following envenomation while many die before arrival to the hospital. With free care for pregnant women and children since 2016 in Burkina Faso, women receive ASV free of charge. This access makes it possible to reduce morbidity and mortality linked to poisoning. Conclusions This report of SBE of women successfully delivered showed that early consultation and administration of ASV can change outcome. It is necessary to sensitize people for early consultation during prenatal care. Funding None. Conflicts of Interest None.

This Invited Commentary accompanies the following original articles: Boenigk K, Echevarria GC, Nisimov E, et al. Low-dose ketamine infusion reduces postoperative hydromorphone requirements in opioid-tolerant patients following spinal fusion: A randomised controlled trial. Eur J Anaesthesiol 2019; 36:8–15. Wang J, Echevarria GC, Doan L, et al. Effects of a single subanaesthetic dose of ketamine on pain and mood after laparoscopic bariatric surgery. A randomised, double-blind, placebo controlled study. Eur J Anaesthesiol 2019; 36:16–24. The studies from Wang et al. 1 and Boenigk et al. 2 published in this issue of the Journal raise fundamental questions about the current position of ketamine within modern multimodal analgesia. 3 Synthesised in 1962 by Calvin Stevens, ketamine was first used in human experiments by Edward Domino and Guenter Corssen of the University of Michigan, who published the first clinical studies more than 50 years ago (1965). They described so-called dissociative anaesthesia, namely an electrophysiological and functional dissociation between thalamocortical and limbic systems. 4 From the outset, it was recognised that ketamine provided potent analgesia, but despite the fact that Sadove et al. 5 showed in 1971 that ‘subdissociative’ doses (0.44 mg kg−1) exhibited analgesic properties with only moderate adverse effects, psychomimetic effects and hallucinations were considered a problematic issue in the early 1970s, and were responsible for the subsequent fall of ketamine into relative oblivion (apart from unusual clinical settings such as shock, burns, cardiac tamponade or asthma). The expansion of the use of remifentanil in the early 1990s changed the story. 6 Its short contextual half-life prompted a regular overdosage routine which was subsequently recognised as responsible for so-called opioid-induced hyperalgesia (OIH). The N-methyl-D-aspartate (NMDA) receptor involvement led to a triumphal comeback of ketamine as a NMDA blocking agent, 6 an action which was soon coined ‘antihyperalgesic’. 7 Nowadays, OIH and the so-called US opioid epidemic 8 which put the spotlight on the respiratory dangers of opioids have triggered a paradigm shift in the management of peri-operative pain. Some anaesthesiologists have dropped the obsolete concept of ‘high-dose fentanyl anaesthesia’ 9 for the promising one of ‘opioid-free anaesthesia’ (OFA). 10,11 In spite of a lack of reduction in the visual analogue pain scores, the study by Wang et al. 1 tells us a new thing: as well as being the ‘actor’ of dissociative anaesthesia, ketamine is also responsible for ‘dissociative analgesia’, that is, preclusion of emotional translation of nociceptive perception. This finding may be put in perspective with the blossoming of ketamine use as a fast antidepressant in patients with a high suicide risk 12 (a property known for more than 40 years 13 and rediscovered about 15 years ago), 14,15 and the recent development of innovative psychedelic therapeutics, including ketamine, in palliative medicine. 16 However, previous works had demonstrated the failure of single ketamine bolus doses to reduce postoperative pain. 17,18 Moreover, boluses of 1 mg kg−1 administered at induction of anaesthesia were clearly inefficient in the recent Prevention of Delirium and Complications Associated with Surgical Treatments trial, where neither pain intensity nor opioid use was diminished. 19 It must be kept in mind that following a bolus dose of 0.5 mg kg−1, ketamine concentration falls beneath 150 ng ml−1 after only 10 min, and less than 25 min after a bolus dose of 1 mg kg−1 (Fig. 1).Fig. 1: The figure shows the plasma concentration obtained according to the Domino model (Rugloop II software; Demed, Temse, Belgium). Two single boluses are illustrated. After a 0.5-mg kg−1 ketamine bolus, plasma concentration falls below 150 ng ml−1 at 10 min. After a 1-mg kg−1 bolus, this concentration is obtained before the 25th minute. A 0.25 mg kg−1 h−1 infusion rate administered after a 0.5-mg bolus gives an analgesic concentration (around 150 ng ml−1) aimed to attain preventive analgesia.Ketamine is a ‘use-dependent’ drug: it blocks NMDA channels only if they have already been opened by intense or repeated noxious stimuli. This ‘foot in the door’ blockade 20 explains why administration prior to the start of surgery is of no peculiar interest. Moreover, the Boenigk et al. 2 study enlightens an interesting part of this fundamental concept: the fact that ketamine is much more efficient when the ‘door has been opened’ by prior use of opioids. We guess that the same happens when NMDA receptors are opened by intense nociceptive stimuli. Indeed, ketamine was shown 17 years ago to prevent chronic postoperative pain after major abdominal surgery, but to achieve this goal, it seems mandatory to use a continuous infusion of at least 0.25 mg kg−1 h−1. 21 Finally, Zakine et al. 22 showed that it could be even better to administer ketamine during the early postoperative days. To conclude, we were told as early as 2005 that continuous administration of ketamine was mandatory for preventive analgesia. 23 Nearly 15 years of use have confirmed that small concentrations of ketamine are safe and have no propensity to trigger the adverse effects (cardiac, cerebral) attributed to hypnotic doses. 2 In the era of OFA, it may be time to consider the use of a continuous infusion of ketamine for noxious surgery or to diminish opioid exposure in endangered patients such as those with respiratory disease, obesity or obstructive sleep apnoea. Acknowledgements relating to this article Assistance with the commentary: none. Financial support and sponsorship: none. Conflicts of interest: none. Comment from the Editor: this Invited Commentary was checked by the editors but was not sent for external peer review. This article was checked and accepted by the Editors, but was not sent for external peer-review.

Snakebites are a real health problem in Morocco because of the diversity of the ophidian fauna and the signifi cant morbidity and mortality if treatment measures are delayed. The Moroccan Poison Control Center reports hundreds of snakebites every year.

To the editorKetamine has been used for more than 50 years, and its safety in anesthesia practice has been definitely established, but the recent PODCAST trial[1][1] confirmed that a single ketamine bolus is of no value for the management of postoperative pain.[2][2] Indeed, it has been recognized

To the Editor,Acute or chronic pain is a socially threatening experience. 1 The majority of the world's population (85%) suffers from physical pain with family, occupational, social, and financial repercussions.Pain remains undertreated, and the reasons for this ''oligoanalgesia'' are inadequate assessment, insufficient knowledge, and negative attitudes. 2 Barriers to pain management are grouped into those related to patients, drug availability, health systems, and health professionals' knowledge and attitudes.In Burkina Faso, there is no policy or training program related to pain, and opioid legislation remains restrictive.At the regional hospital of Koudougou, many patients continue to complain about

To the Editor We read with interest the survey by Hyman et al1 evaluating burnout in anesthesiologists. Their work is seriously constructed (83% response rate, honesty survey), uses several scores, including the Maslach Burnout Inventory (MBI), but as they remark, addresses a peculiar group of physicians attending an American Society of Anesthesiologists webinar. They collected 170 responses and found a 66% incidence of burnout, with 15% having a high score in the 3 MBI components. They were especially interested in evaluating the role of substance abuse. Because they suggest that a study 5 times larger would have been necessary to detect the role of some addictions, and because some of their questions remained unanswered (role of gender, being a physician or a nurse, working in a teaching hospital or not), we thought it would be interesting to compare their work with our own results, from the largest cohort evaluating burnout in French anesthesia personnel in 2009. Our work involved >1600 persons and was published in the French journal of anesthesia.2 Along with the MBI, it included the Fast Alcohol Consumption Evaluation (FACE) and Harvard Department of Psychiatry and National Depression Screening Day Scale (HANDS) scales and questions regarding health, work, and personal life, including addictions. The cohort included 972 men and 622 women: 1091 anesthetists (68%), 241 intensivists (15%), and 204 nurses (13%). Seven hundred sixty-three were working in a university hospital (47%), 405 in a private structure (25%), and 259 in a regional hospital (16%). Thirty-nine percent suffered from depression, 11% were alcohol addicted, and 11% were drug or chemicals addicted. Sixty-two percent were in burnout, and 6% had high scores in the 3 MBI dimensions. Gender, age, being a nurse or a physician, and working in a teaching hospital or private structure were not linked to burnout. Living together as a couple was protective. There was a strong correlation between burnout severity and conflicts, poor sleep quality, mental health, and depression score. Moreover, there was a correlation with alcohol or drug consumption and road accidents after a night shift. As Hyman et al1 state, each burnout study possesses its own biases and explores its specific cohort. Their study detects an astonishingly high proportion of persons with a high score at the 3 MBI components, a condition related to alarming mental and health counterparts in our cohort. Unfortunately, burnout, which largely overlaps with depression,3 is definitely not regressing in France.4 Georges Mion, MDDepartment of Anesthesiology and Intensive Care MedicineCochin HospitalAssistance Publique Hôpitaux de ParisParis, France[email protected] Didier Journois, MDDepartment of Anesthesiology and Intensive Care MedicineCochin HospitalAssistance Publique Hôpitaux de ParisParis, FranceRené Descartes UniversityParis, France Nicolas Libert, MDAnesthesia and Intensive Care DepartmentHôpital d’instruction des armées PercyClamart, France

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. Copyright (C) 2018 Wolters Kluwer Health, Inc. All rights reserved.

Editor—Current guidelines recommend 24–48 h of continuous monitoring in the post-anaesthesia care unit (PACU) for patients undergoing resection of phaeochromocytoma to diagnose postoperative hypotension and hypoglycaemia.1Lenders J.W. Duh Q.Y. Eisenhofer G. et al.Pheochromocytoma and paraganglioma: an endocrine society clinical practice guideline.J Clin Endocrinol Metab. 2014; 99: 1915-1942Crossref PubMed Scopus (1470) Google Scholar We challenged these guidelines and investigated whether a subgroup of patients undergoing adrenalectomy for phaeochromocytoma fulfil criteria for early discharge from the PACU to the ward when haemodynamic data, postoperative pain, postoperative nausea and vomiting (PONV), and glycaemic control are taken into account, as opposed to 24–48 h of postoperative monitoring.1Lenders J.W. Duh Q.Y. Eisenhofer G. et al.Pheochromocytoma and paraganglioma: an endocrine society clinical practice guideline.J Clin Endocrinol Metab. 2014; 99: 1915-1942Crossref PubMed Scopus (1470) Google Scholar The Ethics Committee of Ile de France III, Tarnier-Cochin University Hospital, 89 rue d’Assas, 75006 Paris, France, approved the study and agreed that, in compliance with French regulations, patient consent could be waived. A prospectively maintained single institution computerized database was used to carry out a retrospective investigation of consecutive adult patients undergoing elective unilateral laparoscopic adrenalectomy for phaeochromocytoma from April 1, 2004 to September 30, 2016 with monitoring for 24 h in the PACU in accordance with current guidelines.1Lenders J.W. Duh Q.Y. Eisenhofer G. et al.Pheochromocytoma and paraganglioma: an endocrine society clinical practice guideline.J Clin Endocrinol Metab. 2014; 99: 1915-1942Crossref PubMed Scopus (1470) Google Scholar Before operation, hypotensive drugs previously prescribed in another unit resulting in normal or moderately elevated systemic arterial pressure (AP) were not altered, except for angiotensin-converting enzyme inhibitors and sartans, which were stopped 48 h before surgery.2Lentschener C. Gaujoux S. Tesniere A. Dousset B. Point of controversy: perioperative care of patients undergoing pheochromocytoma removal-time for a reappraisal?.Eur J Endocrinol. 2011; 165: 365-373Crossref PubMed Scopus (91) Google Scholar New hypotensive drugs were administered only for systolic AP (SAP) ≥180 mm Hg, diastolic AP ≥100 mm Hg, or if functional or clinical symptoms such as headache, dizziness, tinnitus, palpitations, or heart disease were recorded.2Lentschener C. Gaujoux S. Tesniere A. Dousset B. Point of controversy: perioperative care of patients undergoing pheochromocytoma removal-time for a reappraisal?.Eur J Endocrinol. 2011; 165: 365-373Crossref PubMed Scopus (91) Google Scholar General anaesthesia was carried out at the discretion of the anaesthetist in charge of the patient using propofol, sufentanil, atracurium, desflurane, or sevoflurane.2Lentschener C. Gaujoux S. Tesniere A. Dousset B. Point of controversy: perioperative care of patients undergoing pheochromocytoma removal-time for a reappraisal?.Eur J Endocrinol. 2011; 165: 365-373Crossref PubMed Scopus (91) Google Scholar Epidural anaesthesia was not used.2Lentschener C. Gaujoux S. Tesniere A. Dousset B. Point of controversy: perioperative care of patients undergoing pheochromocytoma removal-time for a reappraisal?.Eur J Endocrinol. 2011; 165: 365-373Crossref PubMed Scopus (91) Google Scholar An arterial line was inserted for AP monitoring and blood sampling.2Lentschener C. Gaujoux S. Tesniere A. Dousset B. Point of controversy: perioperative care of patients undergoing pheochromocytoma removal-time for a reappraisal?.Eur J Endocrinol. 2011; 165: 365-373Crossref PubMed Scopus (91) Google Scholar I.V. dexamethasone, 8 mg, and droperidol, 1.25 mg, were administered after induction of general anaesthesia, as PONV prophylaxis.3Gan T.J. Diemunsch P. Habib A.S. et al.Consensus guidelines for the management of postoperative nausea and vomiting.Anesth Analg. 2014; 118: 85-113Crossref PubMed Scopus (920) Google Scholar Intraoperative medications included: nicardipine for SAP≥160 mm Hg; norepinephrine for SAP≤90 mm Hg following tumour removal after a fluid challenge of 200 ml lactated Ringer solution to rule out hypovolaemia; and esmolol for heart rate >100 beats min−1 and/or for sustained arrhythmia by bolus doses or by continuous infusion.2Lentschener C. Gaujoux S. Tesniere A. Dousset B. Point of controversy: perioperative care of patients undergoing pheochromocytoma removal-time for a reappraisal?.Eur J Endocrinol. 2011; 165: 365-373Crossref PubMed Scopus (91) Google Scholar The surgical and anaesthetic teams in charge of phaeochromocytoma removal were limited to two or four trained senior practitioners, respectively. Upon arrival in the PACU, dextrose solution was infused until oral feeding was established.2Lentschener C. Gaujoux S. Tesniere A. Dousset B. Point of controversy: perioperative care of patients undergoing pheochromocytoma removal-time for a reappraisal?.Eur J Endocrinol. 2011; 165: 365-373Crossref PubMed Scopus (91) Google Scholar Blood tests including measurement of plasma haemoglobin and electrolyte concentrations were carried out if necessary. After 3 h in the PACU, patients who did not require norepinephrine to treat arterial hypotension, nicardipine to treat arterial hypertension, volume loading for haemodynamic support, supplemental morphine to treat a pain score ≥3, ondansetron to treat PONV, or supplemental dextrose to treat hypoglycaemia under routine dextrose infusion, were assumed eligible for ‘early discharge from the PACU to the ward’.2Lentschener C. Gaujoux S. Tesniere A. Dousset B. Point of controversy: perioperative care of patients undergoing pheochromocytoma removal-time for a reappraisal?.Eur J Endocrinol. 2011; 165: 365-373Crossref PubMed Scopus (91) Google Scholar, 3Gan T.J. Diemunsch P. Habib A.S. et al.Consensus guidelines for the management of postoperative nausea and vomiting.Anesth Analg. 2014; 118: 85-113Crossref PubMed Scopus (920) Google Scholar, 4Aubrun F. Mazoit J.X. Riou B. Postoperative intravenous morphine titration.Br J Anaesth. 2012; 108: 193-201Abstract Full Text Full Text PDF PubMed Scopus (93) Google Scholar Both groups, ‘early discharge to the ward’ and ‘prolonged monitoring in the PACU’, were compared with respect to preoperative and intraoperative data likely to have altered the outcome ‘early discharge from the PACU to the ward’. Out of 152 patients undergoing the procedure, ‘prolonged monitoring in the PACU’ was decided on: (a) before operation for 22 patients with co-existing diseases including catecholamine-induced heart failure operated on after normalization (two of these 22 patients developed acute intraoperative events also warranting prolonged postoperative monitoring in the PACU); and (b) intraoperatively for eight patients because of acute intraoperative events, with 125 patients remaining for assessment at the third postoperative hour in the PACU. Out of these 125 patients, 95 (72%) fulfilled the predefined criteria for ‘early discharge from the PACU to the ward’ and 30 patients (28%) were allocated to the ‘prolonged monitoring group’. Before operation, the two groups did not differ (P>0.05) with respect to patient or phaeochromocytoma characteristics. Postoperative hypoglycaemia was not diagnosed in any patient receiving dextrose infusion. Seven preoperative and intraoperative variables with P≤0.15 in the univariate analysis were included in a logistic regression analysis. In the logistic regression analysis, preoperative SAP, lowest intraoperative SAP, and duration of surgery, remained associated with ‘prolonged monitoring in the PACU’ (P≤0.05) (Table 1). As no cut-off value could be identified, ‘discharge from the PACU’ could only have been decided upon after an individual assessment carried out after 3 h in the PACU.Table 1Preoperative and intraoperative data believed to be associated with ‘prolonged monitoring in the post-anaesthesia care unit’, with P≤0.15 in the univariate analysis. They were included in a logistic regression analysis. Three variables were associated with ‘prolonged monitoring in the PACU’ in the logistic regression analysis (P<0.05). GA, general anaesthesia; SAP, systolic arterial pressureVariableRegression coefficientStandard errorP-valueOdds ratio95% Confidence intervalNumber of preoperative antihypertensive drugs0.0930.510.81.09(0.39–3.02)SAP before induction of GA0.0250.010.0491.03(1.00–1.05)Lowest intraoperative SAP−0.0730.020.0010.93(0.89–0.97)Preoperative normetanephrine concentration0.0200.030.421.02(0.97–1.07)Preoperative metanephrine concentration0.0180.0280.401.00(0.93–1.03)Intraoperative nicardipine requirement0.0420.040.31.04(0.95–1.14)Duration of surgery0.0180.0060.0061.02(1.00–1.03) Open table in a new tab Control of PONV is a prerequisite for discharge from the PACU.3Gan T.J. Diemunsch P. Habib A.S. et al.Consensus guidelines for the management of postoperative nausea and vomiting.Anesth Analg. 2014; 118: 85-113Crossref PubMed Scopus (920) Google Scholar Alpha-blockers with a long half-life are no longer available in France,2Lentschener C. Gaujoux S. Tesniere A. Dousset B. Point of controversy: perioperative care of patients undergoing pheochromocytoma removal-time for a reappraisal?.Eur J Endocrinol. 2011; 165: 365-373Crossref PubMed Scopus (91) Google Scholar but they are still administered in many countries.2Lentschener C. Gaujoux S. Tesniere A. Dousset B. Point of controversy: perioperative care of patients undergoing pheochromocytoma removal-time for a reappraisal?.Eur J Endocrinol. 2011; 165: 365-373Crossref PubMed Scopus (91) Google Scholar, 5Groeben H. Nottebaum B.J. Alesina P.F. Traut A. Neumann H.P. Walz M.K. Perioperative α-receptor blockade in phaeochromocytoma surgery: an observational case series.Br J Anaesth. 2017; 118: 182-189Abstract Full Text Full Text PDF PubMed Scopus (76) Google Scholar We believe that sustained arterial hypotension resulting from their administration would have been detected during the assessment carried out at 3 h after operation, and that administration of these drugs would not have overrule our conclusions. The site of the study is a large tertiary care centre, which takes care of a large number of heterogeneous referrals with various degrees of catecholamine release and arterial hypertension, receiving various types of antihypertensive drugs.2Lentschener C. Gaujoux S. Tesniere A. Dousset B. Point of controversy: perioperative care of patients undergoing pheochromocytoma removal-time for a reappraisal?.Eur J Endocrinol. 2011; 165: 365-373Crossref PubMed Scopus (91) Google Scholar The retrospective design of the study should not be a limitation, as a randomized clinical trial looking for differences in outcomes is not possible as a consequence of both the rarity and heterogeneity of the disease, and the low expected mortality of phaeochromocytoma removal.2Lentschener C. Gaujoux S. Tesniere A. Dousset B. Point of controversy: perioperative care of patients undergoing pheochromocytoma removal-time for a reappraisal?.Eur J Endocrinol. 2011; 165: 365-373Crossref PubMed Scopus (91) Google Scholar In conclusion, 90 out of 152 patients undergoing initial unilateral laparoscopic adrenalectomy for phaeochromocytoma fulfilled predefined criteria for safe, ‘early discharge from the PACU to the ward’ after an individual assessment carried out after 3 h in the PACU. They did not benefit from prolonged monitoring in the PACU. This information is clinically relevant and complies with prevailing opinions regarding early rehabilitation and reducing healthcare costs.6Brennan G.P. Fritz J.M. Houck L.T. Hunter S.J. Outpatient rehabilitation care process factors and clinical outcomes among patients discharged home following unilateral total knee arthroplasty.J Arthroplasty. 2011; 30: 885-890Abstract Full Text Full Text PDF Scopus (18) Google Scholar A prospective study has been initiated with the aim of confirming these findings. Contributed to the study design, analysis, and interpretation of the results, and critically revised and approved the text. Gave final approval to the present version for publication. Are accountable for all aspects of the work, thereby ensuring that questions related to the accuracy or integrity of any part of the work have been investigated appropriately and resolved: all authors. Coordinated the study design, collected data from patient files, and wrote the final manuscript: C.L., S.G. Carried out the statistical analysis: G.M. Assisted in the organization of the study and reviewed the final manuscript several times: C.B., B.D. The authors have no conflicts of interest. Departmental funding only.