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1.  Ethical reflections on end-of-life signs and symptoms in the intensive care setting: a place for neuromuscular blockers? 
The death of a loved one is often an ordeal and a tragedy for those who witness it, as death is not merely the end of a life, but also the end of an existence, the loss of a unique individual who is special and irreplaceable. In some situations, end-of-life signs, such as agonal gasps, can be an almost unbearable “sight” because the physical manifestations are hard to watch and can lead to subjective interpretation and irrational fears. Ethical unease arises as the dying patient falls prey to death throes and to the manifestations of ebbing life and the physician can only stand by and watch. From this point on, medicine can put an end to suffering by the use of neuromuscular blockade, but in so doing life ceases at the same time. It is difficult, however, not to respond to the distress of loved ones and caregivers. The ethical problem then becomes the shift from the original ethical concern, i.e. the dying patient, to the patient’s loved ones. Is such a rupture due to a difference in nature or a difference in degree, given that the dying patient remains a person and not a thing as long as the body continues to lead its own life, expressed through movement and sound? Because there cannot be any simple and unequivocal answer to this question, the SRLF Ethics Commission is offering ethical reflections on end-of-life signs and symptoms in the intensive care setting, and on the use of neuromuscular blockade in this context, with presentations on the subject by two philosophers and members of the SRLF Ethics Commission, Ms Lise Haddad and Prof Dominique Folscheid. The SRLF Ethics Commission hopes to provide food for thought for everyone on this topic, which undoubtedly calls for further contributions, the aim being not to provide ready-made solutions or policy, but rather to allow everyone to ponder this question in all conscience.
PMCID: PMC4098689  PMID: 25045580
Ethics; End of life; Critical care; Gasps
2.  End of life in the intensive care unit: should French law be adapted? 
Longstanding concerns regarding end of life in the ICU led in France to the publication of guidelines, updated in 2009, that take into account the insights provided by a recent law (Leonetti’s law) regarding patients’ rights. After the French President asked a specific expert to review end of life issues, the French Intensive Care Society (SRLF) surveyed their members (doctors and paramedics) about various aspects of end of life in the ICU.
SRLF members were invited to respond to a questionnaire, sent by Email, designed to assess their knowledge of Leonetti’s law and to determine how many caregivers would agree with the authorization of lethal drug administration in selected end of life situations.
Questionnaires returned by 616 (23%) of 2,700 members were analyzed. Most members (82.5%) reported that they had a good knowledge of Leonetti’s law, which most (88%) said they have often applied. One third of respondents had received ‘assisted death’ requests from patients and more than 50% from patients’ relatives. One quarter of respondents had experienced the wish to give lethal drugs to end of life patients. Assuming that palliative care in the ICU is well-managed, 25.7% of the respondents would approve a law authorizing euthanasia, while 26.5% would not. Answers were influenced by the fear of a possible risk of abuse. Doctors and nurses answered differently.
ICU caregivers appear to be well acquainted with Leonetti’s law. Nevertheless, in selected clinical situations with suitable palliative care, one quarter of respondents were in favor of a law authorizing administration of lethal drugs to patients.
PMCID: PMC4015966  PMID: 24568144
Euthanasia; Palliative care; End of life; Intensive care unit
3.  Contribution of the ethics committee of the French Intensive Care Society to describing a scenario for implementing organ donation after Maastricht type III cardiocirculatory death in France 
French law allows organ donation after death due to cardiocirculatory arrest. In the Maastricht classification, type III non-heart-beating donors are those who experience cardiocirculatory arrest after the withdrawal of life-sustaining treatments. French authorities in charge of regulating organ donation (Agence de la Biomédecine, ABM) are considering organ collection from Maastricht type III donors. We describe a scenario for Maastricht type III organ donation that fully complies with the ethical norms governing care to dying patients. That organ donation may occur after death should have no impact on the care given to the patient and family. The dead-donor rule must be followed scrupulously: the organ retrieval procedure must neither cause nor hasten death. The decision to withdraw life-sustaining treatments, withdrawal modalities, and care provided to the patient and family must adhere strictly to the requirements set forth in patient-rights legislation (the 2005 Léonetti law in France) and should not be influenced in any way by the possibility of organ donation. A major ethical issue regarding the family is how best to transition from discussing treatment-withdrawal decisions to discussing possible organ retrieval for donation should the patient die rapidly after treatment withdrawal. Close cooperation between the healthcare team and the organ retrieval team is crucial to minimize the distress of family members during this transition. Modalities for implementing Maastricht type III organ donation are discussed here, including the best location for withdrawing life-sustaining treatments (operating room or intensive care unit).
PMCID: PMC3475084  PMID: 22747673
Organ donation; Treatment withdrawal; Cardiocirculatory arrest
4.  Ventilator-induced lung injury: historical perspectives and clinical implications 
Mechanical ventilation can produce lung physiological and morphological alterations termed ventilator-induced lung injury (VILI). Early experimental studies demonstrated that the main determinant of VILI is lung end-inspiratory volume. The clinical relevance of these experimental findings received resounding confirmation with the results of the acute respiratory distress syndrome (ARDS) Network study, which showed a 22% reduction in mortality in patients with the acute respiratory distress syndrome through a simple reduction in tidal volume. In contrast, the clinical relevance of low lung volume injury remains debated and the application of high positive end-expiratory pressure levels can contribute to lung overdistension and thus be deleterious. The significance of inflammatory alterations observed during VILI is debated and has not translated into clinical application. This review examines seminal experimental studies that led to our current understanding of VILI and contributed to the current recommendations in the respiratory support of ARDS patients.
PMCID: PMC3224506  PMID: 21906379
5.  Beneficial effects of loxapine on agitation and breathing patterns during weaning from mechanical ventilation 
Critical Care  2010;14(3):R86.
Interruption of sedation during weaning from mechanical ventilation often leads to patient agitation because of withdrawal syndrome. We tested the short-term efficacy and tolerance of loxapine in this situation.
Nineteen mechanically ventilated patients with marked agitation after sedation withdrawal were included. Three agitation scales, the Richmond Agitation Sedation Scale (RASS), the Motor Activity Assessment Scale (MAAS), and the Ramsay and physiological variables (respiratory rate, airway occlusion pressure during the first 0.1 second of inspiration (P0.1), heart rate and systolic arterial blood pressure) were recorded before and after loxapine administration.
Loxapine dramatically improved all agitation scores (RASS and MASS decreased from 2 ± 0 to -1.1 ± 2.3, and 5.4 ± 0.5 to 2.7 ± 1.6, respectively; Ramsay increased from 1.0 ± 0 to 3.5 ± 1.5, 60 minutes after loxapine administration, P < 0.05 for all scores) as well as P0.1 (6 ± 4.2 to 1.8 ± 1.8 cm H2O; P < 0.05) and respiratory rate (from 31.2 ± 7.2 to 23.4 ± 7.8; P < 0.05) without hemodynamic adverse events. No side effects occurred. Sixteen (84%) patients were successfully managed with loxapine, sedation was resumed in two others, and one patient self-extubated without having to be reintubated.
Loxapine was safe and effective in treating agitation in a small group of mechanically ventilated patients and improved respiratory physiologic parameters, enabling the weaning process to be pursued. A multicenter trial is under way to confirm these promising results.
PMCID: PMC2911718  PMID: 20459867
6.  Incidence and impact on clinical outcome of infections with piperacillin/tazobactam resistant Escherichia coli in ICU: A retrospective study 
Escherichia coli infections are frequent in ICU patients. The increased resistance to fluoroquinolones and amoxicillin/clavulanate of this pathogen mandates the prescription of broad-spectrum antibiotics such as piperacillin/tazobactam (PIP-TAZ) or third generation cephalosporins (3GC).
To assess incidence and impact on clinical outcome of infections with PIP-TAZ resistant E. coli in ICU patients, we conducted a retrospective cohort study with infections due to PIP-TAZ resistant (PIP-TAZ R) or to PIP-TAZ susceptible strains (PIP-TAZ S) between 1 January 2002 and 30 June 2004.
Of 83 strains, 13 were PIP-TAZ R: 2 strains produced an extended-spectrum β-lactamase (2%), 11 produced a high level penicillinase (13%). Prior amoxicillin or amoxicillin/clavulanate prescription was reported in 7 cases (54%) of infections with PIP-TAZ R isolates and in 15 cases (21%) of infections with PIP-TAZ S isolates (p = 0.03). Time of onset of the infection from hospital admission was longer in case of infections with PIP-TAZ R than with PIP-TAZ S isolates (22 ± 32 vs 10 ± 21 days, p = 0.01). The overall ICU mortality rate was 38%. Mortality and length of stay in ICU were similar in case of infections with PIP-TAZ R isolates and with PIP-TAZ S isolates.
Infections with PIP-TAZ R E. coli are frequent in ICU patients. No prognostic impact of this pattern of resistance was found. Prescription of PIP-TAZ for empirical treatment of E. coli infections in ICU however exposes to inappropriate therapy.
PMCID: PMC2409345  PMID: 18485230
7.  Continuous versus Intermittent Infusion of Vancomycin in Severe Staphylococcal Infections: Prospective Multicenter Randomized Study 
A continuous infusion of vancomycin (CIV) may provide an alternative mode of infusion in severe hospital-acquired methicillin-resistant staphylococcal (MRS) infections. A multicenter, prospective, randomized study was designed to compare CIV (targeted plateau drug serum concentrations of 20 to 25 mg/liter) and intermittent infusions of vancomycin (IIV; targeted trough drug serum concentrations of 10 to 15 mg/liter) in 119 critically ill patients with MRS infections (bacteremic infections, 35%; pneumonia, 45%). Microbiological and clinical outcomes, safety, pharmacokinetics, ease of treatment adjustment, and cost were compared. Microbiological and clinical outcomes and safety were similar. CIV patients reached the targeted concentrations faster (36 ± 31 versus 51 ± 39 h, P = 0.029) and fewer samples were required for treatment monitoring than with IIV patients (7.7 ± 2.2 versus 11.8 ± 3.9 per treatment, P < 0.0001). The variability between patients in both the area under the serum concentration-time curve (AUC24h) and the daily dose given over 10 days of treatment was lower with CIV than with IIV (variances, 14,621 versus 53,975 mg2/liter2/h2 [P = 0.026] and 414 versus 818 g2 [P = 0.057], respectively). The 10-day treatment cost per patient was $454 ± 137 in the IIV group and was 23% lower in the CIV group ($321 ± 81: P < 0.0001). In summary, for comparable efficacy and tolerance, CIV may be a cost-effective alternative to IIV.
PMCID: PMC90678  PMID: 11502515

Results 1-7 (7)