Does uncontrolled cardiac death for organ donation raise ethical questions? An opinion survey.

BACKGROUND: Organ donation after uncontrolled cardiac death raises complex ethical issues. We conducted a survey in a large hospital staff population, including caregivers and administrators, to determine their ethical viewpoints regarding organ donation after uncontrolled cardiac death. METHODS: Multicenter observational survey using a questionnaire, including information on the practical modalities of the procedure. Respondents were asked to answer 15 detailed ethical questions corresponding to different ethical issues raised in the literature. Ethical concerns was defined when respondents expressed ethical concerns in their answers to at least three of nine specifically selected ethical questions. RESULTS: One thousand one hundred ninety-six questionnaires were received, and 1057 could be analysed. According to our definition, 573 respondents out of 1057 (54%) had ethical concerns with regard to donation after cardiac death and 484 (46 %) had no ethical concerns. Physicians (55%) and particularly junior intensivists (65%) tended to have more ethical issues than nurses (52%) and hospital managers (37%). Junior intensivists had more ethical issues than senior intensivists (59%), emergency room physicians (46%) and transplant specialists (43%). CONCLUSION: Only 46% of hospital-based caregivers and managers appear to accept easily the legitimacy of organ donation after cardiac death. A significant number of respondents especially intensivists, expressed concerns over the dilemma between the interests of the individual and those of society. These results underline the need to better inform both healthcare professionals and the general population to help to the development of such procedure.

[Organization of intensive care in situation of avian flu pandemic]. / Organisation de la réanimation en situation de pandémie de grippe aviaire.

The influenza pandemic will create a major increase in demand for hospital admissions, particularly for critical care services. The recommendations detailed herein have been elaborated by experts from medical societies potentially involved in this situation and focus on general hospital organization. Intensive care units will initially face high demand for admission; the Healthcare Authorities must therefore study how ICU capacity can be expanded. Pediatric intensive care units will be particularly affected by this situation of relative bed shortage, since young children, particularly infants, are expected to be affected by severe clinical forms of avian flu. Therefore, the weight threshold for admission to the adult ICU was lowered to 20 kg. Neonatal intensive care units (NICU) should remain, if possible, low viral density areas. Mixed (neonatal and pediatric) intensive care units could be dedicated to infants and children only. NICU admission of extreme premature babies should be limited in this difficult situation. Pediatric intensive care units (PICU) admission capacity could be doubled by using intermediate care and postoperative care units. The staff could be increased by doctors and nurses involved in canceled programmed activities. Healthcare workers transferred to PICU should be given special training.

[The organisation of intensive care in a situation of pandemic avian influenza]. / Organisation de la réanimation en situation de pandémie de grippe aviaire.

The development of an epidemic of avian influenza will have a major impact on the organisation and structure of the facilities for treatment. This paper, the product of collaboration between the six learned societies concerned, analyses the impact of a possible pandemic on the various aspects of management of patients requiring intensive care. It describes the organisation of hospital pathways for flu and non-flu patients with, in particular, the necessary actions in terms of separation of care facilities, the triage of patients and the cancellation of non-urgent activities. It analyses the preconditions necessary for the efficient functioning of intensive care and the predictable limiting factors. It underlines the importance of training of medical and paramedical personnel. Finally, it tackles the specific problems of paediatric intensive care: organisation, capacity for admissions and training.

Alveolar neutrophil oxidative burst and beta2 integrin expression in experimental acute pulmonary inflammation are not modified by inhaled nitric oxide.

It was recently proposed that nitric oxide (NO) inhalation interferes with polymorphonuclear neutrophil (PMN) activation status during acute pulmonary inflammation, although variable results have been observed considering timing of NO administration, species, and model differences. After intratracheal administration of lipopolysaccharide (LPS) in rats, we characterized pulmonary inflammatory reaction (lung wet, dry, and wet to dry weights) and, using flow cytometry, the activation status (H2O2 production and beta2 integrin CD11b/CD18 expression) of PMN obtained from blood and from bronchoalveolar lavage (BAL). Eight hours after LPS injection, rats received for an additional 10 h, at a same Fio2 (85%), either 15 parts per million NO or the same gas flow of nitrogen. We found that 18 h after LPS, lung wet, dry, and wet-to-dry weights, H2O2 production, and CD11b/CD18 expression were increased. PMN obtained from BAL were highly activated as evidenced by an already maximal expression of the beta2 integrin CD11b/CD18, whereas the high H2O2 production at basal state could be further enhanced after ex vivo stimulation. Blood PMN were not different from control cells at basal state; however, their increased capacity to be stimulated ex vivo suggested an in vivo priming effect of intratracheal LPS. In conclusion, inhaled NO, given with a high FiO2, in the presence of this established endotoxinic lung injury did not reverse the markers of PMN activation studied nor lung edema formation in this rat model.

Doppler cardiac output and left ventricular performance after cardiac surgery. Pulsed Doppler ascending aorta and pulmonary blood flows and left ventricular function using implanted microprobes.

We have developed novel implantable Doppler microprobes to monitor beat-by-beat stroke volume and cardiac output (CO) after cardiac surgery. In 11 adults undergoing either coronary artery bypass grafting (n = 6) or valve replacement (n = 5), Doppler microprobes were implanted on the ascending aorta or the main pulmonary artery to measure aortic blood flow (ABF) or pulmonary artery blood flow (PBF). The diameters of both vessels were determined before surgery using two-dimensional echocardiography. Stroke volume was obtained from velocity tracings measured by a 4-MHz zero-crossing pulsed Doppler flowmeter. Simultaneous measurements of Doppler and thermodilution CO (TDCO) were compared. We found the following: ABF = 1.03 TDCO - 0.22 L/min (r = 0.89); while PBF = 0.69 TDCO - 1.24 L/min (r = 0.75). Furthermore, peak flow velocity and maximum acceleration of blood in the ascending aorta were measured after inotropic stimulation with dobutamine; both values increased significantly from control values (25.2 +/- 6.1 percent and 44.6 +/- 8.6 percent, respectively, at 7.5 micrograms/kg/min). We conclude that implanted aortic Doppler microprobes provide a sensitive and reliable method to measure aortic blood flow velocity after surgery and then allow monitoring of stroke volume and CO and analysis of left ventricular function after cardiac surgery.

Interest of a therapeutic optimization strategy in severe ARDS.

STUDY OBJECTIVE: Evaluate the interest of the response to a therapeutic optimization as a predictor of prognosis in ARDS. DESIGN: Prospective study. SETTING: ICU of a University Hospital. PATIENTS: Thirty-six consecutive patients with severe ARDS addressed for extracorporeal carbon dioxide removal (ECCO2R). INTERVENTIONS: We studied the response during the first 2 days after arrival to the therapeutic optimization strategy consisting in a combination of the following: (1) decrease in extravascular lung water (diuretics or hemofiltration); (2) selection of the best ventilatory mode; (3) permissive hypercarbia; and (4) correction of hypoxemia by alveolar recruitment, additional continuous oxygen insufflation, body position changes (prone position), inhaled nitric oxide, enhancement of hypoxic pulmonary vasoconstriction with almitrine, and drainage of pleural or mediastinal effusions. In patients remaining severely hypoxemic despite these modalities, ECCO2R was then proposed. MEASUREMENTS AND RESULTS: Thirty-six patients were addressed after 8.3+/-5.5 days of mechanical ventilation. On arrival, mean simplified acute physiologic score was 46.8+/-14.2, multiple system organ failure score was 1.8+/-1.6, Murray score was 3.4+/-0.4, PaO2 was 75.3+/-31.3 (fraction of inspired oxygen [FIO2]=1) for a positive end-expiratory pressure level of 12.3+/-3.4 cm H2O. Nineteen of 36 patients improved their gas exchange within 2 days and their mortality was 21%. The seventeen remaining patients did not improve PaO2/FIO2; PaCO2 and airway pressures remained high and their mortality was 88%. This different response to therapeutic optimization appeared using stepwise logistic regression as the most predictive factor for mortality (p<0.05). CONCLUSIONS: In patients with severe ARDS, the response to an early performed therapeutic optimization used to improve hypoxemia appeared to be a highly discriminant factor distinguishing deceased from surviving patients.

Interactions between hemodynamic and hormonal modifications during PEEP-induced antidiuresis and antinatriuresis.

The interactions between hemodynamic and hormonal modifications during antidiuresis and antinatriuresis induced by positive end-expiratory pressure (PEEP) were studied in six patients under 15 cm H2O PEEP before PEEP and after the addition of lower body positive pressure (LBPP) to PEEP (PEEP+LBPP). We measured or calculated the following: cardiac index, systemic arterial, right atrial, pulmonary arterial, and pulmonary artery occlusive pressures; indexed renal blood flow (iodohippurate 131 sodium clearance); total blood volume (chromium 51 radiolabeled RBCs); glomerular filtration rate; urinary output; fractional excretion of sodium (FE Na+); plasma concentrations of antidiuretic hormone (ADH), plasma renin activity (PRA), norepinephrine and epinephrine; urinary concentration of PGE2 (PGE2u). Although LBPP application corrected PEEP deleterious effects on systemic and renal hemodynamics, sustained fall in Vu and in FE Na+ were observed. Antidiuresis was not due to ADH release. Sympathetic activation and high PRA appeared the main determinants of renal function alterations in PEEP ventilation.

Systemic pressure-flow reactivity to norepinephrine in rabbits: impact of endotoxin and fluid loading.

OBJECTIVE: This study aimed to evaluate the impact of fluid loading on hemodynamics and vascular hypocontractility to norepinephrine (NE) in an endotoxic shock model. DESIGN: Mean arterial pressure (MAP), aortic blood flow velocity (AoV, 20 MHz Doppler) and aortic conductance (AoC = AoV/MAP) were studied during 180 min (T0-T180) in 41 anesthetized and ventilated rabbits. INTERVENTIONS: Shock was induced by a 600 micrograms/kg bolus injection of endotoxin. Fluid loading (20 ml/kg colloids) was infused from T90 to T120. Dose-response curves to NE were performed at T0, T60 and T120 in endotoxic and non-endotoxic animals with or without fluid loading. MEASUREMENTS AND RESULTS: Endotoxin decreased pressure (-23%, p < 0.05) and flow (-42%, p < 0.05) corresponding to a decrease in conductance (-19%, p < 0.05). Fluid loading did not improve hypotension but markedly increased systemic flow (+51%, p < 0.01), corresponding to a hyperkinetic syndrome. Vascular reactivity to NE was impaired after endotoxin at T60 since the pressure response to NE was depressed (p < 0.01) and flow did not decrease. In non-fluid-loaded groups, the pressure response to NE recovered at T120, with no reduction in flow. In fluid-loaded endotoxic animals, however, the pressure response to NE was still impaired at T120 (p < 0.05), but with a decrease in flow. CONCLUSIONS: Fluid loading transformed the hypodynamic profile of endotoxic shock into a hyperdynamic state without improving blood pressure. Depressed vascular reactivity to NE was observed in both hyperdynamic and hypodynamic states, suggesting that a reduced vascular reactivity does not necessarily imply systemic vasodilation.

Coupled vs. uncoupled pericardial constraint: effects on cardiac chamber interactions.

The effects of pericardial constraint on cardiac chamber interactions were evaluated by mathematical model analyses based on a novel concept of coupled vs. uncoupled pericardial constraint. We hypothesized that the nature of pericardial constraint can be classified as a "coupled" constraint exerted by uniform liquid pressure or an "uncoupled" constraint exerted by regional surface pressure. The numerical solution of the model of atrioventricular interaction produced the characteristic waveforms in venous flows and right atrial/ventricular pressures in classical pericardial diseases. Coupled constraint accounted for the patterns in cardiac tamponade; uncoupled constraint accounted for those in constrictive pericarditis. Analytic solution of the model of ventricular interdependence demonstrated that coupled constraint (tamponade) produced greater gains in ventricular interdependence, increasing the occurrence of pulsus paradoxus, whereas uncoupled constraint (constriction) produced a greater effective right ventricular elastance, increasing the likelihood of Kussmaul's sign. Thus the concept of coupled vs. uncoupled constraint may offer a coherent framework to understand the characteristic steady-state and respiratory-induced hemodynamic events in multiple forms of pericardial diseases.

Nitric oxide in sepsis.

The synthesis of nitric oxide (NO) and its targets are reviewed physiologically during sepsis and wound healing, a self-limiting process in which mechanisms are still identified incompletely. NO also plays an active and direct role during infection, aimed at protecting the host and destroying the microbe. During septic shock, an overproduction of NO has been described experimentally and clinically that might be responsible for the systemic vasodilatation with hyporesponsiveness to exogenous vasoconstrictive agents. The different manipulations of NO pathway during sepsis are described (transcription and post-transcription of iNOS, enzymatic function, substrate availability, NO concentration, and NO effector molecules), although their clinical benefit remains controversial.

Effect of anesthesia and surgery on plasma cytokine levels.

Cytokines released in response to stress may have a profound impact on circulatory stability. There is no information on the effect of general anesthesia alone on plasma cytokine levels and little information on cytokine release following surgery. Plasma cytokine levels and hemodynamic parameters were measured during anesthesia and abdominal surgery under sterile and nonpyrogenic conditions in seven pigs anesthetized with ketamine and pentobarbital. Tumor necrosis factor (TNF) was measured by bioassay. Bioassays of low and high sensitivity were used to measure interleukin 6 (IL-6). Measurements were made sequentially during: (1) 4 hours observation with anesthesia alone; (2) 2 hours following laparotomy and traumatic intestinal manipulation (IM) sufficient to produce shock; and (3) after an intravenous bolus of 1 microgram/kg endotoxin as a positive control. Arterial blood pressure decreased following IM from 91.5 +/- 5.8 to 48.6 +/- 3.2 mm Hg, (mean +/- SE, P < .05), with no further change following endotoxin. Heart rate was unchanged during the experiment, and central venous pressure decreased after endotoxin (P < .05). There were no increases in TNF or IL-6 (using a low sensitivity assay) with anesthesia alone or following IM with shock, but both increased after endotoxin administration (P < .05); using a high sensitivity assay, IL-6 did not change during anesthesia alone but did increase fivefold following IM with shock (P < .05) and 50-fold following endotoxin administration (P < .05). We conclude that in a porcine model under sterile and nonpyrogenic conditions, prolonged anesthesia does not increase plasma cytokine levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Distinct behavior of portal venous and arterial vascular waterfalls in porcine liver.

PURPOSE: Hepatic dysfunction is associated with morbidity and mortality in critically ill patients. Understanding liver hemodynamics in pathological states requires characterization of the normal portal venous and hepatic arterial circulations. Using pressure flow analysis, we tested the hypothesis that vascular waterfalls determine blood flows in the normal liver. METHODS: In 14 vascularly isolated porcine livers, steady-state pressure-flow relationships, which defined a slope (incremental resistance) and a zero flow pressure intercept (Po), were generated for each vessel over a range of hepatic venous pressures (Phv). RESULTS: Critical closing pressures occurred in the portal venous circulation (Po = 3.8 +/- 0.4 mm Hg) with classical waterfall physiology observed as Phv was raised. The hepatic arterial critical closing pressure (Po = 8.3 +/- 1 mm Hg) showed a constant positive pressure difference of mm Hg versus Phv as the latter was increased from 0 to 28 mm Hg (P < .05). Portal venous resistance decreased when Phv was greater than Po (P < .05), but no effect on hepatic arterial resistance was seen as Phv was increased. CONCLUSION: Both critical closing pressures and incremental resistances showed markedly different responses to increased outflow pressures in the portal venous and hepatic arterial circulations. The results provide the physiological basis to analyze hemodynamic changes in the liver under normal and pathological conditions.

[Ventricular tachycardia of ischemic origin. Surgical treatment by encircling thermo-exclusion using the Nd-Yag laser]. / Tachycardies ventriculaires d'origine ischémique. Traitement chirurgical par thermo-exclusion circonférentielle au laser Nd-Yag.

Refractory and recurrent ventricular tachycardias are a common cause of death after myocardial infarction. The occurrence of intraventricular re-entries can be prevented by a new surgical treatment based on encircling thermic exclusion. The Nd-YAG laser beam offers 2 major advantages over previous techniques: it acts rapidly with minimal myocardial damage and can even be used in patients with left ventricular dysfunction.

[Nitrate derivatives and anesthesia-resuscitation: physiopathologic bases and therapeutic indications]. / Dérivés nitrés et anesthésie-réanimation: bases physiopathologiques et indications thérapeutiques.

This review briefly describes the cellular mechanisms of nitrates and the tolerance. Nitrates activate NO production thus GMPc in the smooth muscle cell explaining their vasodilating properties even in absence of an intact endothelium. The biologic pathway of AMPc is stimulated by prostaglandin activated by nitrates. Tolerance to these agents could result from depletion of sulfhydryl radical but also from reflex cardiovascular adaptation. After a brief recall of pharmacokinetic, pharmacodynamic properties are detailed. Therapeutic use in cardiac surgery, non-cardiac surgery, controlled hypotension, aortic surgery, heart failure, unstable angina, myocardial infarction and systolic hypertension in the elderly are discussed.

Incidence and prediction of inadequate preoxygenation before induction of anaesthesia.

BACKGROUND: Preoxygenation aims to obtain an expired oxygen fraction (FEO2)≥90%. Little is known about the incidence and predictors of inadequate preoxygenation in the clinical setting. PATIENTS AND METHODS: Over a 12-month period, 1050 consecutive preoperative patients were prospectively included. Preoxygenation was performed for 3minutes with a facial mask using a machine circuit and 12-L/min oxygen flow. Inadequate preoxygenation was defined as an FEO2<90%. A logistic regression was performed to identify incidence and independent predictors. RESULTS: The patient characteristics were: age 51±20years, 47% male, BMI of 26±5kg/m(2), and ASA score (median [extremes]) of 2 [1-4]. Inadequate preoxygenation was observed in 589 patients (56%). The effective FiO2 delivered was lower in the patients with inadequate preoxygenation than in those with adequate preoxygenation, 95±3% vs. 98±2%, P<0.001. The difference between the FiO2 and the FEO2 was higher (12±6% vs. 6±3%, P<0.0001) in patients with inadequate preoxygenation compared with those with adequate preoxygenation. The independent risk factors for inadequate preoxygenation were: firstly, bearded male (odds ratio [OR] of 9.1 [2.7-31.4] P<0.001); secondly, beardless male (OR 2.4 [1.6-3.4] P<0.001), thirdly, ASA score of 4 (OR 9.1 [2.6-31.2] P<0.015); fourthly, ASA score of 2-3 (OR 2.4 [1.6-3.4] P<0.015); fifthly, lack of teeth (OR 2.4 [1.2-4.5] P<0.006), and lastly age>55 years (OR 1.8 [1.2-2.7] P<0.005). CONCLUSION: Inadequate preoxygenation, defined as an FEO2 <90% despite 3-min tidal volume breathing, was a common occurrence. The predictive factors share an overlap with those previously identified for difficult mask ventilation.

Critical appraisal of organ procurement under Maastricht 3 condition.

The ethics committee of the French Society of Anesthesia and Intensive Care (Sfar) has been requested by the French Biomedical Agency to consider the issue of organ donation in patients after the decision to withdraw life-supportive therapies has been taken. This type of organ donation is performed in the USA, Canada, the United Kingdom, the Netherlands and Belgium. The three former countries have published recommendations formalizing procedures and operations. The French Society of Anesthesia and Intensive Care (Société française d'anesthésie et de reanimation [Sfar]) ethics committee has considered this issue and envisioned the different aspects of the whole process. Consequently, it sounded a note of caution regarding the applicability of this type of organ procurement in unselected patients following a decision to withdraw life-supportive therapies. According to French regulations concerning organ procurement in brain-dead patients, the committee stresses the need to restrict this specific way of procurement to severely brain-injured patients, once confirmatory investigations predicting a catastrophic prognosis have been performed. This suggests that the nature of the confirmatory investigation required should be formalized by the French Biomedical Agency on behalf of the French parliamentarians, which should help preserve population trust regarding organ procurement and provide a framework for medical decision. This text has been endorsed by the Sfar.

[Critical appraisal of organ procurement under Maastricht 3 condition]. / Analyse critique du prélèvement en condition M3 de Maastricht.

The ethics committee of the French Society of Anesthesia and Intensive Care (Sfar) has been requested by the French Biomedical Agency to consider the issue of organ donation in patients after a decision of withdrawing life supporting therapies has been taken. This category of organ donation is performed in the USA, Canada, United Kingdom, the Netherlands and Belgium. The three former countries have published recommendations, which formalize procedures and operations. The Sfar ethics committee has considered this issue and envisioned the different aspects of the whole process. Consequently, it sounds a note of caution regarding the applicability of this type of organ procurement in unselected patient following a decision to withdraw life supporting therapies. According to the French regulation concerning organ procurement in brain dead patients, the committee stresses the need to restrict this specific way of procurement to severely brain injured patients, once confirmatory investigations predicting a catastrophic prognosis have been performed. It suggests that the nature of the confirmatory investigation required should be formalized by the French Biomedical Agency on behalf of the French parliamentarians. This should help preserving population trust regarding organ procurement and provide a framework to medical decision. This text has been endorsed by the Sfar.

[Euthanasia, assisted suicide and palliative care: a review by the Ethics Committee of the French Society of Anaesthesia and Intensive Care]. / Fin de vie, euthanasie et suicide assisté : une mise au point de la Société française d'anesthésie et de réanimation (Sfar).

CONTEXT: Management of the end of life is a major social issue which was addressed in France by law, on April 22nd 2005. Nevertheless, a debate has emerged within French society about the legalization of euthanasia and/or assisted suicide (E/AS). This issue raises questions for doctors and most especially for anesthetists and intensive care physicians. OBJECTIVE: To highlight, dispassionately and without dogmatism, key points taken from the published literature and the experience of countries which have legislated for E/AS. RESULTS: The current French law addresses most of the end of life issues an intensive care physician might encounter. It is credited for imposing palliative care when therapies have become senseless and are withdrawn. However, this requirement for palliative care is generally applied too late in the course of a fatal illness. There is a great need for more education and stronger incentives for early action in this area. On the rare occasions when E/AS is requested, either by the patient or their loved-ones, it often results from a failure to consider that treatments have become senseless and conflict with patient's best interest. The implementation of E/AS cannot be reduced to a simple affirmation of the Principle of autonomy. Such procedures present genuine difficulties and the risk of drift. CONCLUSION: We deliver a message of prudence and caution. Should we address painful end of life and moral suffering issues, by suppressing the subject, i.e. ending the patient's life, when comprehensive palliative care has not first been fully granted to all patients in need of it ?