Papers by David Orlikowski
Intensive Care Medicine, 2021
To study the efficacy of lopinavir-ritonavir and hydroxychloroquine in critically ill patients wi... more To study the efficacy of lopinavir-ritonavir and hydroxychloroquine in critically ill patients with coronavirus disease 2019 (COVID-19). Methods: Critically ill adults with COVID-19 were randomized to receive lopinavir-ritonavir, hydroxychloroquine, combination therapy of lopinavir-ritonavir and hydroxychloroquine or no antiviral therapy (control). The primary endpoint was an ordinal scale of organ support-free days. Analyses used a Bayesian cumulative logistic model and expressed treatment effects as an adjusted odds ratio (OR) where an OR > 1 is favorable. Results: We randomized 694 patients to receive lopinavir-ritonavir (n = 255), hydroxychloroquine (n = 50), combination therapy (n = 27) or control (n = 362). The median organ support-free days among patients in lopinavir-ritonavir, hydroxychloroquine, and combination therapy groups was 4 (-1 to 15), 0 (-1 to 9) and-1 (-1 to 7), respectively,
Respiratory Care, 2016
BACKGROUND: Duchenne muscular dystrophy (DMD) is a sex-linked genetic disorder in which progressi... more BACKGROUND: Duchenne muscular dystrophy (DMD) is a sex-linked genetic disorder in which progressive impairment of skeletal muscle function eventually leads to severe respiratory failure requiring continuous noninvasive ventilation (NIV) at home. A current focus of debate is whether NIV may slow the decline in respiratory function or, on the contrary, worsen respiratory function when started early. Our objective here was to describe the effects of NIV on vital capacity (VC) and maximum respiratory pressures in DMD. METHODS: We analyzed retrospective data from 71 subjects with DMD, including VC, maximum static respiratory pressures, and sniff nasal inspiratory pressure before and after NIV initiation. The declines in these variables from the highest value to the most recent value were computed. RESULTS: Although respiratory function continued to deteriorate over time, NIV introduction was followed by significant slowing in the annual rates of decline in VC (from 4.28 to 1.36 percent predicted), maximum inspiratory pressure (from 2.77 to 1.48 cm H 2 O), and maximum expiratory pressure (from 2.00 to 1.00 cm H 2 O). NIV had no effect on sniff nasal inspiratory pressure. CONCLUSIONS: Introducing NIV in subjects with DMD was followed by slowing of the declines in VC and in maximum static inspiratory and expiratory pressures.
Neuromuscular disorders : NMD, 2017
In neuromuscular disease (NMD) patients, current guidelines recommend the initiation of home mech... more In neuromuscular disease (NMD) patients, current guidelines recommend the initiation of home mechanical ventilation (HMV) in case of daytime hypercapnia or nocturnal desaturation as an indirect sign of hypoventilation. Transcutaneous capno-oximetry (TcCO2) enables the direct assessment of nocturnal hypercapnia; however the best cut-off value remains to be defined. We aimed to compare the prognostic value of several published definitions of nocturnal hypercapnia in a cohort of NMD patients. All consecutive TcCO2 recordings performed between 2010 and 2014 in unventilated adult NMD patients in a tertiary reference centre were retrospectively collected. Initiation of HMV and mortality were collected as outcomes of interest. 124 patients with normal daytime blood gazes were analysed (median age 39 [IQR 31-55] years; vital capacity 61% [43-82] of predicted). The prevalence of nocturnal hypercapnia ranged from 3% to 44%, depending on the definition. Over a median follow-up duration of 2.5 ...
Orphanet journal of rare diseases, Mar 16, 2017
Respiratory muscle strength is a proven predictor of long-term outcome of neuromuscular disease (... more Respiratory muscle strength is a proven predictor of long-term outcome of neuromuscular disease (NMD), including amyotrophic lateral sclerosis, Duchenne muscular dystrophy, and spinal muscular atrophy. Maximal inspiratory pressure (MIP), a sensitive measure of respiratory muscle strength, one of several useful tests of respiratory muscle strength, is gaining interest as a therapeutic clinical trial endpoint for NMD. In this comprehensive review we investigate the use of MIP as a measure of respiratory muscle strength in clinical trials of therapeutics targeting respiratory muscle, examine the correlation of MIP with survival, quality of life, and other measures of pulmonary function, and outline the role of MIP as a clinically significantly meaningful outcome measure. Our analysis supports the utility of MIP for the early evaluation of respiratory muscle strength, especially of the diaphragm, in patients with NMD and as a surrogate endpoint in clinical trials of therapies for NMD.
La Lettre Du Pneumologue, 2005
Virologie, Oct 1, 2011
Le syndrome de Guillain-Barre (SGB), premiere cause des paralysies aigues dans les pays industria... more Le syndrome de Guillain-Barre (SGB), premiere cause des paralysies aigues dans les pays industrialises, fait suite, dans la majorite des cas, a une maladie infectieuse ; le cytomegalovirus (CMV) est l’un des agents les plus frequemment mis en cause. Les donnees disponibles concernant le SGB associe au CMV proviennent d’etudes relativement anciennes portant sur des series limitees de patients. En analysant les donnees cliniques et biologiques de plus de 500 patients hospitalises entre 1996 et 2006 en reanimation a l’hopital Raymond-Poincare (Garches), nous avons pu etudier plus de 60 cas de SGB faisant suite a une primo-infection par CMV. Les donnees que nous avons rassemblees confirment certaines caracteristiques cliniques classiquement decrites. De plus, sur cette serie de patients, nous avons mis en evidence de nouveaux elements epidemiologiques et identifie des facteurs de risque de sequelles neurologiques a long terme. Enfin, l’etude des viremies suggere un possible role direct du virus dans le processus physiopathologique, mais la part de la replication virale dans le developpement du SGB reste a etablir.
European Respiratory Journal, 2015
Background: Home mechanical ventilation (HMV) is used to treat hypoventilation, and its efficacy ... more Background: Home mechanical ventilation (HMV) is used to treat hypoventilation, and its efficacy is mostly assessed by daytime blood gases and nocturnal oximetry (SpO2). Transcutaneous CO2 measure (TcCO2) has shown higher sensitivity than SpO2 to detect hypoventilation in neuromuscular diseases (NMD) patients. No data exists on the prognostic value of these techniques. Aims: We aimed to compare the prognostic value of SpO2 and TcCO2 in ventilated adult NMD patients. Methods: Capno-oximetries performed between 2009 and 2011 in ventilated adult NMD patients were analyzed retrospectively and classified as showing “hypoxemia”, “hypercapnia” or being “normal”. Patients on oxygen therapy were excluded. Time to first ICU admission or death was collected as outcome of interest. Results: 55 patients were analyzed (age 28 [IQR 25-36.5] years; 71% Duchenne muscular dystrophy; vital capacity 11.5 [7.25-27.25] % of predicted; 51% tracheostomy). Capno-oxymetry was normal in 67% of patients, showing hypoxemia in 15% and hypercapnia in 27%. 9% had both hypoxemia and hypercapnia. Over a median follow-up of 4 years, we observed 12 deaths and 21 ICU admissions. The diagnosis-adjusted hazard ratio (95%CI) for mortality or ICU admission was 2.93 (1.24-6.91, p=0.01) for hypercapnia and 2.31 (0.85-6.23, p=0.10) for hypoxemia, when compared to the group with normal capno-oxymetry. Conclusions: Residual hypoventilation, assessed by capno-oximetry, has a negative prognostic impact in adult ventilated NMD patients. Accordingly, we suggest that capno-oxymetry should be included in the assessment of HMV efficacy in NMD patients, since TcCO2 identifies more patients at risk than oximetry alone.
Anesthésie & Réanimation, 2015
Sleep and Breathing, 2015
Purpose Restrictive respiratory failure is a major cause of morbidity and mortality in neuromuscu... more Purpose Restrictive respiratory failure is a major cause of morbidity and mortality in neuromuscular diseases (NMD). Home mechanical ventilation (HMV) is used to treat hypoventilation, identified by daytime hypercapnia or nocturnal desaturation. Recently, transcutaneous measure of CO 2 (TcCO 2) has been increasingly used to detect hypoventilation, using different cutoffs. We aimed to compare the prevalence of hypoventilation in an unselected adult NMD population according to different definitions issued from the literature. Methods All consecutive nocturnal capno-oximetries performed between 2010 and 2014 in unventilated adult NMD patients were analysed retrospectively. Concomitant blood gas analysis and lung function data were collected. Patients on oxygen therapy were excluded. Hypoventilation was defined according to eight criteria, based on daytime PaCO 2 , daytime base excess, nocturnal SpO 2 or TcCO 2. Results Data from 232 patients were analysed (mean age 43.1 ±15.4 years; 50.0 % women; vital capacity 59.2±24.2 % of predicted). The hypoventilation prevalence was 10.3 to 61.2 %, depending on the used definition. The different definitions showed 49.1 to 94.8 % concordance (Cohen's kappa for agreement 0.115 to 0.763). Overall agreement between the eight definitions was poor (Light's kappa 0.267), and agreement between definitions based on nocturnal SpO 2 and those based on TcCO 2 was even lower (Light's kappa 0.204). Conclusions We found large differences in hypoventilation prevalence according to the used definition. This has practical consequences, as HMV indication relies upon hypoventilation detection. We believe that capno-oximetry should be included in the diagnostic tools used to detect hypoventilation but this requires an update of consensus guidelines to agree upon the best definition.
SUMMARY Some muscular diseases are characterized by respiratory impairment principally due to dia... more SUMMARY Some muscular diseases are characterized by respiratory impairment principally due to diaphragmatic weakness. The respiratory management of these patients is based on a better understanding the impact of respiratory failure on chest wall biomechanics. Optoelectronic plethysmography (OEP), using a three dimensional motion analysis system, can be used to evaluate respiratory impairment from chest wall compartment kinematics using a three-dimensional model and allow quantification of coordination between compartments. The aim of this preliminary study was to use OEP in order to identify early indicators of the diaphragmatic weakness and to characterize ventilatory patterns in neuromuscular patients with Pompe’s disease. Three patients with Pompe’s disease and five healthy subjects were included. Spirometry, ventilatory pattern and compartmental chest wall kinematics were assessed using OEP during spontaneous breathing (SB), slow vital capacity (SVC) and sniff maneuver, in a sup...
Revue des Maladies Respiratoires Actualités, 2014
Nutrition Clinique et Métabolisme, 2007
Introduction et but de l’etude La denutrition est frequente dans la myopathie de Duchenne de Boul... more Introduction et but de l’etude La denutrition est frequente dans la myopathie de Duchenne de Boulogne (DMD) (50% a l’âge de 18), d’autant que le pronostic de vie de ces patients s’est allonge grâce aux progres de la prise en charge. Elle est probablement un facteur pronostique pejoratif a l’origine de complications trophiques, d’un risque infectieux respiratoire accru. Cette etude multicentrique retrospective descriptive rapporte l’experience de la nutrition enterale par gastrostomie (GS) dans la DMD. Materiel et methodes Les 26 patients DMD inclus etaient suivis a Lille et Garches, necessitaient une gastrostomie par voie percutanee endoscopique (n=19), radiologique (n=3) ou chirurgicale (n=2) entre 1997 et 2007 en raison de denutrition (n=20) et/ou de troubles de deglutition (n=11). L’evaluation de l’etat nutritionnel a 0, 3, 6, 9, 12 mois et a la date de recul maximal se faisait grâce aux rapports poids sur âge (P/A) par rapport aux courbes de Griffiths et Edwards. Les complications precoces, tardives et a long terme etaient relevees. Une relation temporelle entre la degradation respiratoire et nutritionnelle etait recherchee. Resultats Aucune mortalite n’etait liee a la nutrition enterale ou a la pose de GS. 17 patients presentaient au moins une complication. Les complications precoces etaient: nausees (n=4), vomissements (n=1), douleurs abdominales (n=7), pneumoperitoine (n=3 : 2 spontanement resolutifs, 1 associe a une perforation oesophagienne traitee chirurgicalement), pneumopathie d’inhalation (n=1), abces parietal (n=2). Les complications tardives et a long terme etaient: vomissements (n=3), nausees (n=1), bourgeonnement de l’orifice (n=6), fuites (n=5), douleurs parietales (n=3), migration parietale de sonde (n=1), ulcere bulbaire (n=2). Il existait une augmentation significative du rapport P/A entre la pose de GS et le recul maximal (medianes 69 % versus 85% respectivement), mais sans rejoindre 100 %. La GS etait realisee a un âge plus tardif (p=0.000003) chez les patients ventiles avant la GS (n=19) que chez les non ventiles avant GS (n=7). Conclusions La gastrostomie d’alimentation entraine peu de complications severes dans la DMD, permet d’ameliorer l’etat nutritionnel, bien que partiellement. Une assistance respiratoire retarde l’âge de la gastrotomie, suggerant que la correction precoce d’une insuffisance respiratoire puisse retarder la denutrition et la necessite d’une gastrostomie.
La Revue du praticien, 2013
Revue des maladies respiratoires, 2007
Revue des Maladies Respiratoires Actualités, 2012
Confrontations anatomo-cliniques, coordonnées par Ph. Bonniaud et J. Cadranel Fil orange CPLF-Res... more Confrontations anatomo-cliniques, coordonnées par Ph. Bonniaud et J. Cadranel Fil orange CPLF-Respirer avec une maladie neuromusculaire, coordonné par D. Montani Numéro réalisé avec le soutien institutionnel de Novartis.
Therapies, 2015
-Les dispositifs médicaux (DM) couvrent une large variété de produits. Ils accompagnent, au gré d... more -Les dispositifs médicaux (DM) couvrent une large variété de produits. Ils accompagnent, au gré des innovations technologiques, l'évolution des pratiques médicales. Les innovations dans le champ du DM peuvent améliorer les conditions d'utilisation de la technologie de santé et/ou modifier l'organisation des soins au-delà du strict bénéfice thérapeutique ou diagnostique pour le patient. Cependant, ces critères non purement cliniques semblent n'être que rarement documentés ou pris en compte dans l'évaluation des DM lors des décisions de remboursement au niveau national ou de référencement au niveau des établissements de santé alors même que des modèles d'évaluation multidimensionnelle des technologies de santé, prenant en compte le point de vue de l'ensemble des acteurs du système de santé, ont été élaborés. Dans cet article, après avoir rappelé le contexte de l'évaluation des technologies de santé en France, une définition des critères d'évaluation non clinique des DM est proposée et un arbre de décision pour l'évaluation des DM est décrit. Des pistes de réflexion sont proposées en conclusion. Abréviations : voir en fin d'article. † Les articles, analyses et propositions des Ateliers de Giens n'engagent que leurs auteurs et ne préjugent pas de la position de leur organisme de tutelle.
Cochrane Database of Systematic Reviews, 2000
Chronic alveolar hypoventilation is a common complication of many neuromuscular and chest wall di... more Chronic alveolar hypoventilation is a common complication of many neuromuscular and chest wall disorders. Long term nocturnal mechanical ventilation is used to treat an increasing number of patients. To examine the efficacy of nocturnal mechanical ventilation in relieving hypoventilation related symptoms in patients with neuromuscular or chest wall disorders. Search of the Cochrane Neuromuscular Disease Group register for randomized trials and enquiry from authors of trials and other experts in the field. Types of studies: quasi-randomized or randomized controlled trials patients with neuromuscular or chest wall disorder-related stable chronic hypoventilation of all ages and all degrees of severity. Types of interventions: any type and any mode of nocturnal mechanical ventilation. Types of outcome measures: Primary: short term and long term reversal of hypoventilation related clinical symptoms Secondary: unplanned hospital admission rate, one year mortality, short term and long term reversal of day time hypercapnia, improvement of lung function and improvement of sleep breathing disorders. We identified four randomized trials. One author extracted the data and another checked them. Individual data were available from the authors of the largest study. The four eligible trials included a total of 51 patients. The risk difference (proportion of patients) of no improvement of hypoventilation related clinical symptoms in the short term following nocturnal mechanical ventilation was significant and favoured treatment, -0.417 (95% CI -0.639 to -0.194). However, there was significant heterogeneity across the studies (p<0.001). Similarly, the risk difference of no reversal of day time hypercapnia in the short term following nocturnal ventilation was significant and favoured treatment, -0.635 (95% CI -0.874 to -0.396). The weighted mean difference of nocturnal mean oxygen saturation percent was 5.5 (95% CI 1.5 to 9.4) more improvement in patients treated with nocturnal mechanical ventilation. For the primary and most of the secondary outcome measures there was no significant difference between nocturnal mechanical ventilation and no ventilation in the long term, except for one-year mortality. Indeed, the risk difference of death one year following implementation of nocturnal mechanical ventilation was significant and favoured treatment, -0.259 (95% CI -0.478 to -0. 041). However, there was significant heterogeneity across the studies (p<0.001). Most of the secondary outcomes were not assessed in the eligible trials. No data could be summarised for the comparisons between invasive and non-invasive mechanical ventilation, between intermittent positive pressure and negative pressure ventilation, and between volume-cycled and pressure-cycled ventilation. Current evidence about the therapeutic benefit of mechanical ventilation is weak, but consistent, suggesting alleviation of the symptoms of chronic hypoventilation in the short term, and in two small studies survival was prolonged. Mechanical ventilation should be offered as a therapeutic option to patients with chronic hypoventilation due to neuromuscular diseases. Further larger randomized trials are needed to confirm long term beneficial effects of nocturnal mechanical ventilation on quality of life, morbidity and mortality, to assess its cost-benefit ratio, and to compare the different types and modes of ventilation.
Journal de Radiologie, 2009
Objectifs Connaitre les principales maladies neuromusculaires et leurs complications viscerales l... more Objectifs Connaitre les principales maladies neuromusculaires et leurs complications viscerales les plus frequentes. Connaitre les indications de la TDM dans les complications viscerales des affections neuromusculaires. Savoir analyser le parenchyme pulmonaire et les bronches sur un examen TDM avec reconstructions 2D et 3D chez un patient ayant une scoliose neuromusculaire. Messages a retenir Radio de thorax et echographie cardiaque sont necessaires pour le suivi evolutif des maladies neuromusculaires, particulierement maladie de Duchenne et myopathie de Steinert. La TDM thoracique fait avec precision le bilan des compressions bronchiques et parenchymateuses des patients ayant une scoliose neuromusculaires ce qui est particulierement utile dans le bilan prechirurgical. La TDM thoracique permet le diagnostic des consequences de l’encombrement bronchique et des complications infectieuses en cas de decompensation respiratoire particulierement en cas de deformation thoracique ou d’arthrodese. La TDM abdominale est necessaire devant un syndrome occlusif ou subocclusif, frequent chez ces patients. Resume Les maladies neuromusculaires ont des profils polymorphes. Leurs manifestations respiratoires et cardiovasculaires sont frequentes et graves. Les troubles respiratoires par musculature incompetente et encombrement bronchique s’ajoutent aux complications d’une frequente scoliose. La TDM complete les cliches en situation aigue et pour le bilan du retentissement de la scoliose. L’echocardiographie evalue la cardiomyopathie. Les dysfonctionnements moteurs digestifs par atteinte de la musculature sont analyses par opacification conventionnelle, et TDM en situation aigue. Un dysfonctionnement urinaire est possible chez ces patients dont la longevite actuelle beneficie du suivi et du traitement. L’imagerie d’affections frequentes ou particulieres est abordee.
EMC - Anestesia-Rianimazione, 2014
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Papers by David Orlikowski