Papa GUEYE

Dr Papa GUEYE

As a hospital practitioner in university hospitals for several years, I was involved in care, teaching and clinical research, as well as training and supervising medical students, interns and other healthcare professionals. After several years' involvement in clinical research, and with a view to directing the research work of young doctors, the defence of this dissertation with a view to obtaining the Habilitation à Diriger des Recherches (HDR) diploma from the University of Guyana is the crowning achievement of this career.

Medical referral
My skills in Clinical Toxicology were acquired during 12 years of clinical activity in the Medical and Toxicological Intensive Care Unit at the Lariboisière - Fernand Widal University Hospital in Paris, a reference service for the management of serious acute intoxications. This clinical experience was combined with clinical and experimental research into the physiopathological mechanisms of acute respiratory failure in toxic comas. My research work in this field was the subject of a PhD thesis defended in 2002.

 Care activities
As a clinician at the bedside, and full-time in intensive care, emergency, SAMU and SMUR, I have always played an active role in care, on-call duties and continuity of care.

Teaching activities
My university teaching activity has been rich, as I have had the opportunity to teach in 1^er and 2^th I was also involved in coordinating and/or participating in the teaching of several university or inter-university diplomas in Paris. When I was transferred to Martinique in 2017, I co-coordinated the teaching of the DESC in Emergency Medicine, then the DES in Emergency Medicine. In September 2020, I was appointed Associate Professor of Emergency Medicine at the Medical Sciences Department of the University of the West Indies. I have set up two University Diplomas in Vital Emergencies and Medical Evacuations in acute and critical situations. Because these two fields of emergency medicine are important areas of activity in the French West Indies and French Guiana, and consequently of required competence for doctors practising in these territories.

Research activities
My research followed my clinical career in Medical and Toxicological Intensive Care, then in pre-hospital Emergency Medicine at the SAMU/SMUR. My research has focused on 1) the pathophysiological mechanisms of acute respiratory failure in toxic comas, 2) the pre-hospital management of severe septic states and septic shock.

Research into toxic comas has led to greater precision in the indications and efficacy of flumazenil, a specific benzodiazepine antagonist, and a better understanding of the functional impairment of the muscles of the upper airways during toxic comas involving benzodiazepines and/or in association with other psychotropic drugs, in particular the inhibition of control of the dilator muscles of the pharynx leading to hypopnoea or even obstructive apnoea, to better define the picture of acute obstructive respiratory failure and the complete reversibility of these disorders by flumazenil and therefore the role of GABA receptors._A involved in this dysfunction and their reversibility. Our research has also shown the role of opiates/opioids in potentiating neurological and respiratory depressant effects when combined with other psychotropic drugs such as alcohol or benzodiazepines. This research was carried out to study the mechanisms of toxicity and death reported with the misuse of high-dose buprenorphine or polyconsumption associating this substitution opioid with heroin addiction. Clinical studies have shown an increase in the annual incidence of serious acute intoxication by buprenorphine, in parallel with the increase in sales and the high frequency of associated detection of benzodiazepines. These results confirm the diversion and misuse of this prescription for withdrawal purposes, as well as the harmful interaction with benzodiazepines, which are also frequently associated with poly-drug use.

The experimental aspect of this research in rats was based on toxicity studies and functional respiratory exploration techniques in rats and invasive exploration of the muscles of the upper airways and diaphragm, and finally on the pharmacokinetic and pharmacodynamic relationships of this interaction between benzodiazepines and buprenorphine and the metabolic interference of these toxins via the same cytochrome P3A4 pathway. Finally, this deleterious interaction at the level of respiratory control could result from a summation of actions on the different neuromuscular components of respiration.

The second area of research concerned the management of sepsis and septic shock in the pre-hospital setting, with a view to improving the management of life-threatening emergencies. The main objectives of this research were: 1) to improve screening and early diagnosis, 2) to improve recognition of severity through the use of simple parameters, 3) to improve prognosis through early and combined treatments of antibiotic therapy without delay and correction of circulatory failure through early haemodynamic optimisation. This collaborative, multi-centre research has led to a number of studies, the results of which will contribute to better diagnostic and prognostic assessment in the emergency context, as well as to improved management. With the aim of improving the detection and assessment of the severity of severe sepsis/septic shock in pre-hospital care by EMS teams, we have demonstrated the value of the shock index (Heart Rate/Systolic Blood Pressure), mottling and skin recolouring time as simple, easily measurable parameters for assessing the severity of the septic state. These studies made it possible to 1) develop a new pre-hospital septic shock triage score, 2) evaluate clinical scores and clinical or biological criteria for predicting mortality in patients with severe sepsis/septic shock pre-hospital. We showed that the SIGARC clinical score, the Charlson Comorbidity Score (CCS) and lactataemia measured in the pre-hospital phase were associated with mortality in patients with septic shock in the pre-hospital phase.

Other studies in which I participated and/or which I coordinated, also in the field of sepsis/septic shock in the pre-hospital setting, demonstrated the importance of the early implementation of treatments from the pre-hospital management stage, combining the pre-hospital administration of broad-spectrum antibiotics, early haemodynamic optimisation with vascular filling and the use of vasopressors. We have shown that pre-hospital administration of norepinephrine reduces 30-day mortality in patients with septic shock, and that its immediate association with appropriate antibiotic therapy further reduces mortality in these patients with septic shock. 

Current and future research projects
My current and future projects are focused on research into improving the management of life-threatening emergencies, in collaboration with teams in Guadeloupe and French Guyana. A number of research projects funded by the Martinique University Hospital's Local Project Calls are currently underway, including an assessment of the management of status epilepticus (EME), an evaluation of the adequacy of management for patients with asthma exacerbations, and a study of the characteristics and prognosis of cardiac arrest in the French West Indies. This work on cardiac arrest will include experimental work on the mitochondrial pathophysiological mechanisms involved in the irreversibility or refractory nature of CA, and on the cellular effects of therapies as a function of the time taken to administer them. This work, under my co-supervision and that of Professor Rémi NEVIERE (EA 7525 UA), is the thesis of a doctoral student, Dr Florian NEGRELLO, who is currently an assistant clinical supervisor in the department. Other funded projects are currently being finalised. These are the TRAUMA DOM study " Evaluation of the Vittel criteria for pre-hospital triage of severe trauma patients in the French West Indies and Guyana". This study, which is also being funded by the Martinique University Hospital's APL, will be a collaborative, multi-centre study involving the Guadeloupe and French Guiana. Finally, the SAMU-ALFENTA study "Comparison of morphine and alfentanil in the emergency treatment of severe acute pain", funded by the PHRCI is in the process of being validated by the CPP and is due to start in 2023.

Other projects are in the process of being submitted or assessment tools such as the SUPARTRI "Evaluation of the suPAR biomarker as a triage tool in the emergency management of patients with suspected sepsis in the French West Indies" or l'CVO-ANTALGIE study "Intranasal sufentanil versus intravenous morphine in the initial analgesic treatment of vaso-occlusive crisis in sickle cell disease".

Conclusion
I've learnt a lot from my teachers and colleagues, without whom I wouldn't be at this level. I have worked and collaborated with several other researchers and their teams. A relationship of mutual trust and mutual support has been established for several years with most of them, and more recently with other colleagues in the West Indies and French Guiana since my arrival in Martinique in 2017. All these collaborations have been, and will continue to be, conducive to developing translational clinical research, particularly in the field of emergency medicine, and also to mentoring and guiding young people in their research, projects and academic careers.

Introduction
As a hospital practitioner in teaching hospitals for several years, I was involved in both care, teaching and clinical research, but also in training and mentoring medical students, residents and other health professionals. After several years of participation in clinical research and with a view to directing the research work of young doctors, I am presenting this work in order to obtain the diploma of "Habilitation à Diriger les Recherches" (HDR) at the University of Guyana.

Medical orientation
I have a triple competence in Emergency Medicine, Intensive Medicine and Resuscitation and Clinical Toxicology. My skills in Clinical Toxicology were acquired through a clinical activity for 12 years in Medical Resuscitation and Toxicology at University Hospital Center Lariboisière - Fernand Widal in Paris, a reference service in the management of severe acute intoxications. This clinical experience was associated with clinical and experimental research in the understanding of the pathophysiological mechanisms of acute respiratory insufficiency of toxic comas. My research in this field was the subject of a Thesis in Science defended in 2002.

Care activities
Clinician at the bedside, and full time in Intensive Care, Emergency Department, SAMU and SMUR, I have always been actively involved in care, guards and therefore in the continuity of care.

Teaching activities
My university teaching activity was rich, as I had the opportunity to teach in the 1st and 2nd cycle of medical studies in several medical school in Paris, to coordinate and/or participate in the teaching of several university or interuniversity degrees in Paris. In Martinique in 2017, I co-coordinated the teachings of the Emergency Medicine. In September 2020, I was appointed Associate Professor in Emergency Medicine at the Medical School at the University of the West Indies. I have set up two University Degrees in the field of Vital Emergencies and Health Evacuations in acute and critical situations. Because these two fields of Emergency Medicine are important fields of activity in the West Indies and Guyana and therefore of competence required for physicians in these territories.

Research activities
My research areas have followed my clinical path in Medical Resuscitation and Toxicology, then in Pre-hospital Emergency Medicine at Emergency Medical Service named SAMU. This research therefore focused on: 1) the physiopathological mechanisms of acute respiratory failure of toxic comas, 2) the pre-hospital management of severe septic conditions and septic shock.

Research on toxic comas has made it possible to clarify the indications and efficacy of flumazenil, a specific antagonist of benzodiazepines, to have a better understanding of the functional impairment of upper airway muscles in toxic comas involving benzodiazepines and/or in combination with other psychotropic drugs, in particular inhibition of the control of the dilatory muscles of the pharynx causing hypopnea or obstructive apnea, To better clarify the clinical presentation of obstructive acute respiratory failure and the complete reversibility of these disorders by flumazenil and therefore the role of the GABA_A receptors involved in this dysfunction and their reversibility. Our research has also shown the role of opiates/opioids in the potentiation of neurological and respiratory depressants when combined with other psychotropic drugs such as alcohol or benzodiazepines. This research was conducted to study the mechanisms of toxicity and death reported with the misuse of high-dose buprenorphine or polyconsumption associating this substitution opioid for heroin addiction. Clinical work has shown an increase in the annual incidence of severe acute buprenorphine poisoning, along with increased sales and the associated high frequency of detection of benzodiazepines. These results confirm the diversion and misuse of this prescription for weaning, but also the deleterious interaction with benzodiazepines which are also frequently associated in a multiple-consumption conduct.

The experimental part of this research in rats was based on toxicity studies and techniques of respiratory functional exploration in rats and invasive exploration of upper airway and diaphragm muscles and finally on relationships Pharmacokinetics and pharmacodynamics of this benzodiazepines and buprenorphine interaction and metabolic interferences of these toxicants by the same cytochrome P3A4 pathway. Finally, this deleterious interaction at the level of respiratory control could result from a summation of actions on the different neuromuscular components of breathing.

The second line of research concerns the management of sepsis and septic shock in pre-hospital in a theme of improving the management of vital emergencies. The main objectives of this research were: 1) to improve screening and early diagnosis, 2) to improve the recognition of severity through the use of simple parameters, 3) improve prognosis through early and combined antibiotic therapy without delay and correction of circulatory failure through early hemodynamic optimization. This collaborative, multi-centre research has led to several studies whose results will contribute to better diagnostic and prognostic assessment in the context of the emergency, but also to better management. In order to improve the screening and evaluation of the severity of severe sepsis/septic shock in pre-hospital supported by SAMU teams, we showed the interest of the shock index (Heart Rate/Systolic Blood Pressure), mottling and cutaneous recoloration time as simple, easily measurable parameters for assessing the severity of septic condition. These studies have allowed 1) to develop a new pre-hospital septic shock triage score, 2) to evaluate clinical scores and clinical or biological criteria to predict mortality of patients with severe sepsis/septic shock in pre-hospital. We showed that the SIGARC clinical score, the Charlson comorbidity score or lactate measured at the pre-hospital setting were associated with the mortality of patients in pre-hospital septic shock.

Then other work in which I participated and/or coordinated, always in sepsis/septic shock in pre-hospital, have shown the importance of early implementation from the time of pre-hospital treatment management and that combine pre-hospital administration of broad spectrum antibiotics, Early hemodynamic optimization with vascular filling and the use of vasopressors. Thus, we showed that pre-hospital administration of norepinephrine reduced mortality to 30 days in patients with septic shock and that its initial association with adapted antibiotic therapy further reduced mortality in these patients in shock septic.

Current and future research projects
My current and future projects are oriented towards research on improving the management of vital emergencies and in collaboration with the teams of Guadeloupe and Guyana. Several research projects funded by the Local Calls for Projects (LCP) of the University Hospital Center of Martinique are being carried out, such as the evaluation of the management of status epilepticus disease, the evaluation of the adequacy of management of patients with asthma exacerbation or the study on the particularities and prognosis of cardiac arrest in the Caribbean. This work on cardiac arrest will have an experimental part on the mitochondrial physiopathological mechanisms of irreversibility or refractory character of cardiac arrest, on the cellular effects of therapies according to the delivery times. This work, under my co-direction and that of Professor Rémi NEVIERE (EA 7525 UA), is the thesis of a PhD student, Dr Florian NEGRELLO, currently assistant head of clinic in the service. Other funded projects are being finalized. This is the TRAUMA DOM study "Evaluation of the Vittel criteria for pre-hospital triage of severe trauma patients in the French West Indies-Guyana". This study, also funded by the LCP of University Hospital Center of Martinique, will be collaborative and multi-centre with Guadeloupe and Guyana. Finally, the SAMU-ALFENTA study "Comparison between morphine and alfentanil in the emergency treatment of severe acute pain", funded by national hospital clinical research program (PHRCI) is being validated for a start expected in 2023.

Other projects are currently being submitted or evaluated, such as the SUPARTRI study " Evaluation of the suPAR biomarker as a triage tool in the emergency management of patients suspected of sepsis". or the CVO-ANTALGIA study "Intranasal sufentanil versus intravenous morphine in the initial analgesic treatment of the vaso-occlusive crisis of sickle cell anaemia."

Conclusion
I learned a lot from my teachers and colleagues, without whom I would not be at this level. I have worked and collaborated with several other researchers and their teams. A relationship of mutual trust and mutual assistance has been established for many years with most of them, and more recently with other colleagues from the West Indies and Guyana since my arrival in Martinique in 2017. All these collaborations have been and will continue to be conducive to the development of translational clinical research and in particular in the field of emergency medicine and also to supervise and direct young people in their research, their academic projects and careers.