Gilbert Bejjani - Academia.edu (original) (raw)

Papers by Gilbert Bejjani

Acta anaesthesiologica Belgica, 1989

Pediatric Research, 2006

Endothelins (ET) have opposite vascular effects mediated through different receptors: ET A recept... more Endothelins (ET) have opposite vascular effects mediated through different receptors: ET A receptors mediating vasoconstriction and ET B receptors mediating vasoconstriction as well as vasodilation. The role of ET in acute hypoxic pulmonary vasoconstriction (HPV) was studied after dual ET receptor blockade with bosentan and nitric oxide (NO) synthase inhibition with nitro-Larginine (L-NA). We started from the hypothesis that ET antagonism may inhibit HPV but, if not, would do so after NO synthase inhibition. HPV was evaluated in anesthetized lambs, with an intact pulmonary circulation, by the increase in the mean pulmonary artery pressure (Ppa) minus occluded Ppa (Ppao) gradient in response to hypoxia (inspiratory oxygen fraction of 0.1) at different levels of pulmonary flow (multipoint pressure/flow relationships). ET receptor antagonism decreased pulmonary and systemic vascular tone both in hyperoxia and hypoxia. ET antagonism had no effect on HPV. NO synthase inhibition increased pulmonary vascular tone more in hypoxia than in hyperoxia so that HPV was enhanced. After L-NA, bosentan still decreased pulmonary vascular tone in hypoxia but did not affect the magnitude of HPV. The present results suggest that ET and NO are involved in the regulation of basal pulmonary vascular tone. Furthermore, the vasodilator effect of bosentan persisted in the presence of NO synthase inhibition, suggesting a non NO-dependent vasodilator mechanism. The results from these experiments are in agreement with the idea that ET do not play a major role in HPV in the perinatal lamb, even when it is enhanced by NO synthase inhibition.

European Respiratory Journal, 2003

The effects of endothelin receptor blockade on the pulmonary circulation have been reported varia... more The effects of endothelin receptor blockade on the pulmonary circulation have been reported variably, possibly in relation to a more or less important associated release of endogenous nitric oxide (NO). The aim of this study was to test whether endothelin antagonism would inhibit hypoxic pulmonary vasoconstriction, and if it would not, then would it do so after NO synthase inhibition. Hypoxic pulmonary vasoconstriction (HPV) was evaluated in anesthetised dogs by the increase in the mean pulmonary artery pressure (Ppa) minus occluded Ppa (Ppao) gradient in response to hypoxia (inspiratory oxygen fraction of 0.1) at constant pulmonary blood flow. Bosentan, an endothelin A and B receptor antagonist, did not affect baseline Ppa, Ppao or systemic arterial pressure (Psa) and did not alter HPV (n=8). The NO synthase inhibitor N G-nitro-L-arginine (L-NA) did not affect baseline Ppa and Ppao, but increased Psa and enhanced HPV (n=12). The addition of bosentan in these dogs did not affect baseline Ppa or Ppao, but decreased Psa and inhibited HPV. Exhaled NO was decreased by L-NA and by bosentan and abolished by L-NAzbosentan (n=9). The authors conclude that endogenous nitric oxide is released by, and opposes the vasoconstricting effects of, endothelins in vivo, reducing systemic blood pressure and limiting hypoxic pulmonary vasoconstriction.

Acta anaesthesiologica Belgica, 2006

Noxious stimulation may enhance implicit learning during general anesthesia. It is unknown, howev... more Noxious stimulation may enhance implicit learning during general anesthesia. It is unknown, however, whether analgesic state can influence this memory processing. Twenty healthy adult volunteers were enrolled our prospective, double-blinded, controlled experiments. Anesthesia was induced with a propofol target controlled infusion (TCI), titrated in step-wise increments to loss of consciousness. In phase A, a 10-word list was played to the subjects while a noxious stimulus was applied (hand immersion in cold water at 2-4 degrees C). In phase B, a remifentanil TCI infusion was added to the steady-state propofol TCI anesthesia, and titrated to loss of hand movement on cold water immersion. A second 10-word list was then played while maintaining the hand in cold water. Memory testing, 2 hours post-recovery revealed no evidence of explicit memory in any subject during either phase of the study. During phase A, the word stem completion test revealed implicit learning for played words. In ...

Journal of Cardiothoracic and Vascular Anesthesia, 2009

Objective: Auditory information presented during anesthesia can activate memory. Surgical stimula... more Objective: Auditory information presented during anesthesia can activate memory. Surgical stimulation may enhance memory formation. The authors' hypothesis is that implicit memory processing is not preserved during unconsciousness, even in the presence of a surgical stimulus. Design: A double-blind randomized controlled trial. Setting: A single-institution, university hospital. Participants: Thirty-eight adults undergoing cardiac surgery. Interventions: Patients were randomized to continuously hear either disc A or B during surgery. On each disc, 20 different words were recorded. Measurements and Main Results: Implicit and explicit memory were tested. The study design was that each group served as a control for the other. The responses from both groups on both lists allowed the authors to compare the likeliness of correctly identifying the words from a list whether it was heard while under anesthesia or not. During the interview, no patient had explicit recall as investigated by the free recall test, and no one reported dreaming. As for implicit memory processing, the difference between the mean rate of correct answers on the word-stem completion test for the disc the patients heard (3.42% for disc A and 13.15% for disc B) or did not hear (3.15% for disc A and 14.73% for disc B) was not statistically significant (p ‫؍‬ 0.95 for A and p ‫؍‬ 0.42 for B). Conclusions: Explicit and implicit memory were not detectable in patients anesthetized with an effect-site targetcontrolled infusion of propofol and remifentanil with bispectral index monitoring. These results suggest that there is no memory processing under anesthesia in the surgical setting.

Journal of Anaesthesiology Clinical Pharmacology, 2012

European Journal of Anaesthesiology, 2010

Background and objective Replacing mixed venous oxygen saturation (SvO 2) monitoring by central v... more Background and objective Replacing mixed venous oxygen saturation (SvO 2) monitoring by central venous oxygen saturation (ScvO 2) monitoring in order to avoid the use of a pulmonary artery catheter and its related complications is still controversial in the setting of cardiac surgery. The influence of surgery, cardiopulmonary bypass and anaesthesia drugs on the relationship between SvO 2 and ScvO 2 has never been studied. Methods Fifteen patients scheduled for cardiac surgery with cardiopulmonary bypass were included in the study. SvO 2 (from the pulmonary artery) and ScvO 2 (from the superior vena cava) were continuously measured with fibre-optic catheters from induction of anaesthesia to 24 h postoperatively. Results A total of 9267 pairs of measurements were recorded. Mean bias between SvO 2 and ScvO 2 was 4.4% with limits of agreement of À13.6 and R22.5%, respectively. Trends of SvO 2 and ScvO 2 values followed very different patterns for some patients. Surgery, cardiopulmonary bypass and anaesthesia drugs did not influence the relationship between the two methods. Conclusion Because of the large interindividual variability in the difference between SvO 2 and ScvO 2 , the measure of ScvO 2 should not replace the measure of SvO 2 with a pulmonary artery catheter for the management of patients undergoing cardiac surgery with cardiopulmonary bypass.

European Journal of Anaesthesiology, 2006

infusion of P until loss of standard clinical signs. Anesthesia was maintained with a perfusion p... more infusion of P until loss of standard clinical signs. Anesthesia was maintained with a perfusion pump according to manual infusion scheme proposed by Roberts 1. Patients had BIS and SBP recorded at all times (including baseline values). Four blood samples (in order to measure blood concentration, Cs) were collected from each subject, at predose, at the end point and at fixed intervals of 15 and 30 min. Reduction in SBP, [(SBP-80)/(SBP baseline-80)]*100, was used as a measure of P effect and related to Cs using a semicompartmental model in order to obtain k e0. Ce (effect site concentration) was then estimated and a pharmacodynamic (PD) model was used to describe the data (WinNonLin Professional, Pharsight Corp.). Results: 21 (10 M and 11 W) out of the total 58 patients did not present drop in SBP during the 30 min of data record although BIS values were at most 60. These patients were excluded from analysis. The remaining (37 patients) showed a significant hysteresis (lag-time between Cs and SBP). The first order rate constant k e0 , was 0.67 min Ϫ1 both in M and in W. Estimated Ce at induction was less in W although no statitical differences were found due to large variability (4.50 vs 6.12 mcg/mL W and M respectively). A sigmoid E max model best described the data (Ce vs effect). PD parameters (ECe50 and ␥) did not show statistical gender dependence. Conclusions: No PD differences were found for P routine protocol anesthesia between M and W for the SBP endpoint. SBP is possibly an inadequate surrogate of anesthesic effect during the first 30 min of surgery. References:

Annales Françaises d'Anesthésie et de Réanimation, 2010

Lettres à la ré daction É valuation de la tolé rance aiguë au ré mifentanil par le monitorage de ... more Lettres à la ré daction É valuation de la tolé rance aiguë au ré mifentanil par le monitorage de la dilatation pupillaire Evaluation of acute remifentanil tolerance with pupil dilation monitoring Nous avons lu avec inté rêt l'article de Coquin et al. [1] sur l'apparition rapide d'une tolé rance aiguë au ré mifentanil sous anesthé sie mise en é vidence par le monitorage de la dilatation pupillaire. Les auteurs montrent en effet une augmentation significative du diamè tre pupillaire 45 minutes aprè s le dé but d'une perfusion continue de ré mifentanil à 0,3 mg/kg par minute (pré cé dé e d'un bolus de 0,25 mg/kg par minute en une minute) en

Anesthesiology, 2006

To the Editor:-We read with great interest the article by Dr. Gijsenbergh et al. 1 about the reve... more To the Editor:-We read with great interest the article by Dr. Gijsenbergh et al. 1 about the reversal of rocuronium-induced neuromuscular block by Org 25969. The described reversal mechanism is highly promising both for the clinical application and in research endeavors. This being the first description of the pharmacokinetics of Org 25969, we hoped to reconstruct the time course of the plasma concentrations of Org 25969 using the provided data. Unfortunately, the combination of the pharmacokinetic parameters (tables 6 and 7) does not permit such a reconstruction, in part due to a nonstandard method of analysis. The authors do not mention whether an exponential equation or a compartmental model was fitted to the concentrations of Org 25969 in plasma. Was either approach even attempted? The terminal elimination half-life (t ½␤) could be appropriate for either a biexponential or a triexponential equation. The reported values for the areas under the plasma concentration curves are, in concept, dose dependent, and the reported values apparently reflect this. Presumably, the authors used areas under the plasma concentration curves to justify the claim of "doselinear pharmacokinetics," but this was not explicitly stated in the text. The reported "volume of distribution during the terminal phase" (V Z) is not routinely reported, and a comparison with the standard volumes, i.e., the initial volume of distribution for a multiexponential equation (V c), the volume of the central compartment in compartmental interpretation (V 1), or the volume of distribution at steady state (V SS), is difficult if not impossible. Furthermore, because V Z was evaluated from V Z ϭ CL/Ϫ␤, V Z is a function of t ½␤ and, hence, provides no additional information. Of the routinely reported parameters, the authors provide only the estimates for the systemic clearance (CL) and the mean residence time. These two parameters do not suffice to reconstruct the time course of the plasma concentrations. It would have been informative had the authors compared the doses of Org 25969 with the dose of rocuronium using molar units. The dose of rocuronium, 0.6 mg/kg, corresponds to approximately 1 • 10 Ϫ6 mol • kg Ϫ1. Given the molecular weight of Org 25969 of 2,000 Da, 2 the doses of Org 25969, 0.1 to 8.0 mg/kg, correspond to (0.05 to 4) • 10 Ϫ6 mol • kg Ϫ1. If one molecule of Org 25969 binds to one molecule of rocuronium and assuming that the whole dose of rocuronium is still present in the body 3 min after injection, then Org 25969 doses of less than 1 • 10 Ϫ6 mol • kg Ϫ1 , corresponding to less than 2 mg/kg, would, on theoretical basis, have little chance to reverse the neuromuscular block completely. As documented by the authors, only the molar doses of Org 25969 higher than the molar dose of rocuronium produced the desired reversal. Therefore, Org 25969 doses of 4.0 and 8.0 mg/kg efficiently reversed the block (table 9); on the molar basis, the two doses are two and four times higher than the dose of rocuronium. The Org 25969 dose of 2 mg/kg is equimolar to that of rocuronium and produced only a marginal reversal of neuromuscular block. Consideration of the doses in molar terms strengthens the authors' conclusion and explains why lower doses of Org 25969 could not have produced the reversal (table 9).

Anesthesia & Analgesia, 2007

DI-fusion, le Dépôt institutionnel numérique de l'ULB, est l'outil de référencementde l... more DI-fusion, le Dépôt institutionnel numérique de l'ULB, est l'outil de référencementde la production scientifique de l'ULB.L'interface de recherche DI-fusion permet de consulter les publications des chercheurs de l'ULB et les thèses qui y ont été défendues.

Acta Anaesthesiologica Belgica, 2008

Intensive care medicine, 2003

To investigate the effects of endogenous endothelins on pulmonary haemodynamics and gas exchange ... more To investigate the effects of endogenous endothelins on pulmonary haemodynamics and gas exchange in oleic acid lung injury. Prospective experimental study in dogs. Animal research laboratory in a university teaching hospital. SUBJECTS. Seventeen anaesthetised and ventilated mongrel dogs. Nine pretreated dogs received an infusion of the endothelin A and B receptor antagonist bosentan (10 mg/kg) started before oleic acid. Eight treated dogs received bosentan started 90 min after oleic acid. Cardiac index (CI) was manipulated by inflating an inferior vena caval balloon or by opening a femoral arterio-venous bypass. Pulmonary vascular resistance was defined by measuring the gradient between mean pulmonary artery pressure (MPAP) and occluded PAP (PAOP) at five levels of CI. Intrapulmonary shunt was measured using the inert gas SF(6). Pretreatment with bosentan prevented the oleic acid-induced shift of (MPAP-PAOP)/CI plots to higher pressures, but did not affect the increase in intrapulmo...

Clinical Nephrology, 2015

Kidney disease Improving Global Outcomes (KDIGO) guidelines strongly recommend administering an a... more Kidney disease Improving Global Outcomes (KDIGO) guidelines strongly recommend administering an anti-IL-2R mAb (i.e., basiliximab) for induction in all kidney transplant recipients. We describe a life-threatening episode of shock following basiliximab injection and review the literature. A 20-year-old male was given tacrolimus, methylprednisolone, mycophenolate, and basiliximab, 20 mg in the context of living-related kidney transplantation. On post-operative Day 1 (POD 1), he developed acute respiratory distress syndrome (ARDS), shock, multiple organ failure, and had a cardiac arrest. After effective resuscitation, he received rescue therapies (NO inhalation, extra-corporeal membrane oxygenation, and CVVHD) but lost the graft as the result of cortical necrosis. We conducted PubMed searches that yielded 7 similar cases; 6 required invasive ventilation. Three patients developed cardiac arrest, 3 required major inotropic support, and 2 developed MOF and myocardial depression. All but 1 patient recovered rapidly within a few days. There was no evidence for infectious, allergic, or over-hydration concerns. Although the direct causal role of basiliximab cannot be formally proven, the fact that ARDS at the time of induction therapy with other immunosuppressive agents is otherwise extremely rare suggests a direct role for basiliximab. Basiliximab could be associated with shock and ARDS.