[Development of a tool for withholding and withdrawing life-sustaining treatment in the emergency room]. / Élaboration et validation d'une fiche d'aide à la décision de limitation ou d'arrêt des traitements aux urgences.

OBJECTIVES: Active treatment withholding and withdrawing decisions in the emergency room (ER) must be taken collegially according to ethical and juridical statements. Specific tools can support this process and our main goal was to create and validate such a tool. METHOD: We created a first version of a tool to help for treatment withholding and withdrawing decisions inspired by similar documents from literature. Every item of this tool was then assessed by a group of experts (ER physicians and nurses) using the Delphi method to reach a consensus. RESULTS: Thirty-four experts from eleven ER (academic, regional centre) were included and participate to the first round and twenty-seven to the second round. From the eighty-two-item tool, sixty-five items reach a consensus during these two rounds and were kept to constitute the final version of the tool. CONCLUSION: We have been able to create a tool to help for treatment withholding and withdrawing decisions adapted to the guidelines for end of life patient's management in the ER. This tool has been validated using a Delphi method by a group of experts from different centres. This multicentre validation will help for the diffusion and use of this tool in the different ER of the Rhône-Alpes region.

[Anticoagulation and antiphospholipid syndrome: be careful to the catastrophe]. / Anticoagulation et syndrome des antiphospholipides : attention à la catastrophe.

Antiphospholipid syndrome associate thromboembolic events (arterial or venous), and presence of antiphospholipid antibodies, and require anticoagulation. A catastrophic variant may develop, resulting in multiorgan failure, with high mortality rate. This article presented a patient with antiphospholipid syndrome presenting a catastrophic antiphospholipide syndrome after anticoagulation suspending for gastrointestinal bleeding. Multidisciplinary management in intensive care unit and aggressive therapies (corticosteroids, anticoagulation, plasma exchange) were essential to rescue the patient.

[Preliminary results in standardization of flow cytometry protocols for monocytic HLA-DR measurement and their application in the follow up of septic shock]. / Standardisation de la mesure de l'antigène HLA-DR monocytaire par cytométrie en flux: résultats préliminaires et application dans le suivi des chocs septiques.

In septic shock, the diminished HLA-DR expression on monocytes has been proposed as a marker of immunoparalysis that correlates with an increased risk for fatal outcome. The present study was designed to determine whether some differences in protocol procedures could lead to discrepant results in HLA-DR measurement. After establishing a reliable protocol, the second objective was to illustrate the immunoparalysis in patients with septic shock. HLA-DR measurement on monocytes was determined by means of flow cytometry in 54 healthy donors and 16 patients with septic shock. We demonstrated that storage temperature, storage duration before staining and red cells lysis constitute crucial steps in HLA-DR measurement. The precision results with coefficients of variation below 5%, were quite convincing for a manual immunoassay. At 48 hours after diagnosis of septic shock, we found severely decreased percentages of monocytes expressing HLA-DR in septic patients (24 +/- 4%, mean +/- SEM) in comparison with healthy donors (90 +/- 1%), p < 0.001). Furthermore, the persistence of a low level of monocytic HLA-DR (less than 50 %) at day 9 after admittance was associated with patients who died. This study illustrates the state of immunoparalysis in patients with septic shock and supports the potential interest in measuring HLA-DR expression on monocytes. However, multicenter studies are now needed to validate this parameter. Based on our analytical results, we conclude that a critical issue in such studies will be the capacity in each center to perform standardized measurement of HLA-DR. It should be remembered that this determination requires the definition of a common analytical procedure between laboratories participating in the trial.

Sequential extracts of human bone show differing collagen synthetic rates.

Type I collagen is the major bone protein. Little is known quantitatively about human bone collagen synthesis in vivo, despite its importance for the understanding of bone formation and turnover. Our aim was to develop a method that could be used for the physiological and pathophysiological investigation of human bone collagen synthesis. We have carried out preliminary studies in patients undergoing hip replacement and in pigs to validate the use of the flooding dose method using (13)C- or (15)N-labelled proline and we have now refined our techniques to allow them to be used in a normal clinical or physiological setting. The results show that the application of a flooding dose causes bone free-proline labelling to equilibrate with that of blood in pigs and human beings, so that only 150 mg of bone will provide enough sample to prepare and measure the labelling of three fractions of bone collagen (dissolved in NaCl, acetic acid and pepsin/acetic acid) which have the same relative labelling (1.0:0.43:0.1) as measured by GC-combustion-isotope ratio MS. The rates of incorporation were substantially faster than in skeletal muscle samples taken at the same time. The results suggest that different fractions of human bone collagen turnover at markedly higher rates than had been previously considered. This approach should allow us to discover how growth and development, food, activity and drugs affect bone collagen turnover and to measure the effects on it of ageing and bone disease.

Latency and duration of stimulation of human muscle protein synthesis during continuous infusion of amino acids.

1. The aim of this study was to describe the time course of the response of human muscle protein synthesis (MPS) to a square wave increase in availability of amino acids (AAs) in plasma. We investigated the responses of quadriceps MPS to a approximately 1.7-fold increase in plasma AA concentrations using an intravenous infusion of 162 mg (kg body weight)(-1) h(-1) of mixed AAs. MPS was estimated from D3-leucine labelling in protein after a primed, constant intravenous infusion of D3-ketoisocaproate, increased appropriately during AA infusion. 2. Muscle was separated into myofibrillar, sarcoplasmic and mitochondrial fractions. MPS, both of mixed muscle and of fractions, was estimated during a basal period (2.5 h) and at 0.5-4 h intervals for 6 h of AA infusion. 3. Rates of mixed MPS were not significantly different from basal (0.076 +/- 0.008 % h(-1)) in the first 0.5 h of AA infusion but then rose rapidly to a peak after 2 h of approximately 2.8 times the basal value. Thereafter, rates declined rapidly to the basal value. All muscle fractions showed a similar pattern. 4. The results suggest that MPS responds rapidly to increased availability of AAs but is then inhibited, despite continued AA availability. These results suggest that the fed state accretion of muscle protein may be limited by a metabolic mechanism whenever the requirement for substrate for protein synthesis is exceeded.

Haemodialysis with the biocompatible high permeability AN-69 membrane does not alter plasma insulin-like growth factor-I and insulin-like growth factor binding protein-3.

BACKGROUND: Insulin-like growth factor-I (IGF-I) bioactivity has been reported to be decreased in maintenance haemodialysis patients and this may affect their nutritional status. Clearances of IGF-I and its binding proteins (IGFBPs) during haemodialysis sessions using a high permeability biocompatible membrane are unknown. METHODS: Five well nourished, non-diabetic adult patients were studied during one 4-h morning haemodialysis treatment using the high permeability biocompatible AN-69 dialyser. Blood was collected at the arterial and venous ports of the dialyser at 0, 1, 2 and 4 h of dialysis for haematocrit, plasma IGF-I, IGFBP-3 and insulin measurements. IGF-I, IGFBP-3 and insulin concentrations were adjusted for haemoconcentration before comparisons were made. RESULTS: At the beginning of the dialysis session, plasma IGF-I, IGFBP-3 and insulin levels were within the normal range (297 +/- 47 ng/ml (mean+/-SEM), 4.3 +/- 0.6 microg/ml and 11.8 +/- 3.4 microIU/ml, respectively). During the session, insulin tended to be cleared through the dialyser, whereas plasma IGF-I and IGFBP-3 values did not vary significantly. CONCLUSION: Dialysis with the high permeability AN69 membrane did not alter the main blood compounds of the IGF system in well nourished chronic haemodialysis patients, and it is unlikely that the malnutrition frequently observed in such patients would result from alterations of the IGF system during haemodialysis.

[Acute dissection of the ascending thoracic aorta complicated by myocardial infarct: an unavoidable diagnostic pitfall?]. / Dissection aiguë de l'aorte thoracique ascendante compliquée d'infarctus du myocarde: un piège diagnostique inévitable?

BACKGROUND: Acute dissection of the aorta during myocardial infarction is exceptional. In such cases, fibrinolysis can be fatal. CASE REPORTS: A 63-year-old woman with a history of hypertension was referred to our intensive care unit with the diagnosis of early stage inferior myocardial infarction. Thrombolysis was instituted and the patient rapidly developed cardiovascular collapse with global heart failure. Coronarography was attempted to revascularize the occluded coronary artery but the coronary arteries could not be catheterized. An aortography was performed and gave the diagnosis of De Bakey type I dissection of the aorta. The patient died from cardiac arrest after a phase of low cardiac output. DISCUSSION: This case illustrates how myocardial infarction can complicate or mask acute dissection of the aorta. It also raises the question of transthoracic echocardiography prior to institution of fibrinolysis.

A randomized study assessing the systematic search for maxillary sinusitis in nasotracheally mechanically ventilated patients. Influence of nosocomial maxillary sinusitis on the occurrence of ventilator-associated pneumonia.

The objective of this randomized study was to compare the occurrence of nosocomial pneumonia in nasotracheally intubated patients who were randomly allocated either to a systematic search of sinusitis by CT scan (study group) or not (control group). A total of 399 patients were included: 272 male and 127 female; mean age, 61 +/- 17 yr; SAPS: 12.6 +/- 4.9. The study group consisted of 199 patients and the control group consisted of 200. In the study group, sinus CT scans were performed in case of fever at Days 4 and 8 and then every 7 d. Nosocomial sinusitis was defined as follows: fever of >/= 38 degrees C, radiographic (sinusal air-fluid level or opacification on CT scan) signs, and presence of purulent aspirate from the involved sinus puncture with >/= 10(3) cfu/ml. Patients with sinusitis received sinus lavage and intravenously administered antibiotics. In the study group, 80 patients experienced nosocomial sinusitis. In the control group, no patient was treated for a sinusitis. Ventilator-associated bronchopneumonia (VAP) was observed in 88 patients: 37 in the study group (1 mo Kaplan-Meier estimate, 34%) versus 51 in the control group (1 mo Kaplan-Meier estimate, 47%); (p = 0.02, log-rank test; relative risk [RR] = 0.61; 95% confidence interval [CI], 0.40 to 0.93). Two months overall mortality was estimated at 36% in the study group versus 46% in the control group (p = 0.03, log-rank test; RR = 0.71; 95% CI, 0.52 to 0.97). We conclude that the occurrence of VAP in patients undergoing prolonged mechanical ventilation via a nasotracheal intubation can be prevented by the systematic search and treatment of nosocomial sinusitis. The effect on mortality should be confirmed.

IGF-I binding proteins, IGF-I binding protein mRNA and IGF-I receptor mRNA in rats with acute renal failure given IGF-I.

BACKGROUND: Recombinant human insulin-like growth factor-I (rhIGF-I) accelerates recovery from acute renal failure (ARF) in rats. IGF-I acts through the IGF-I receptor (IGF-IR) and its actions may be modified by IGF-I binding proteins (IGFBPs). It therefore would be of value to determine the effects of both ARF and rhIGF-I treatment on serum IGFBPs and mRNA for IGFBPs and IGF-IR. METHODS: Rats with ARF and sham-operated control rats were randomized to receive rhIGF-I or vehicle injections thrice daily for 72 to 74 hours starting five hours after surgery. Serum IGFPBs 1 to 6 were measured serially, and mRNA for IGFBPs 1 to 6 and for IGF-IR were measured in several tissues obtained 72 to 74 hours after surgery. RESULTS: At 72 to 74 hours, serum IGFBP-1 and IGFBP-2 levels were higher in rhIGF-I treated rats. Serum IGFBP-3 was affected by both ARF and rhIGF-I. IGFBP-4 rose transiently only in ARF groups. At 72 to 74 hours, mRNA for several IGFBPs was reduced in renal cortex of ARF rats. Low mRNA for IGFBP-4 and -6 was observed in renal medulla of the ARF rats, particularly in comparison to the sham-operated rats receiving vehicle. Renal medullary IGFBP-2 mRNA was decreased in ARF and sham rats given rhIGF-I as compared to sham animals given vehicle. Hepatic IGFBP-2 mRNA was higher in both rhIGF-I treated groups versus those given vehicle. Otherwise, there were no differences in IGFBP mRNAs among the four groups in lung, heart, and skeletal muscle. IGF-IR mRNA was decreased in renal cortex and medulla of both ARF groups and was not detected in liver in any group. CONCLUSIONS: Thus, ARF and rhIGF-I treatment each affected certain serum IGFBPs and jointly affected some IGFBPs. ARF suppressed gene transcription for renal cortical and medullary IGF-IR and some IGFBPs. rhIGF-I independently affected some renal cortical or medullary IGFBP mRNAs. rhIGF-I increased hepatic IGFBP-2 mRNA and serum IGFBP-2. These effects of ARF or rhIGF-I may influence rhIGF-I actions in rats with ischemic ARF.

[Use of insulin-like growth factor-I (IGF-I) in the treatment of acute renal insufficiency]. / Utilisation d'insulin-like Growth Factor-I (IGF-I) dans le traitement de l'insuffisance rénale aiguë.

Despite numerous progresses, including extracorporeal epuration, acute renal failure (ARF) remains associated with a high level of mortality and morbidity, particularly in intensive care unit. Experimental research on different acute renal failure models has clearly shown that growth factors and particularly Insulin-like Growth Factor I (IGF-I) can reduce renal injury, improve renal recovery and even reduce mortality. IGF-I, that is locally produced in injured renal tubules, promotes the proliferation and differentiation of new tubular cells. Moreover, IGF-I carriers (IGFBPs) and IGF-I receptor are altered in ARF and modify the growth factor bioactivity. To date, only two clinical trials studied IGF-I treatment in the ARF condition. Other studies are required to demonstrate a role for IGF-I in treating or preventing acute renal failure.

[How many patients with acute myocardial infarction can be treated by thrombolysis?]. / Wie viele Patienten mit akutem Herzinfarkt können mit Thrombolyse behandelt werden?

Thrombolytic treatment of acute myocardial infarction (MI) is limited by the time elapsed since onset, accuracy of the diagnosis and the presence of contra-indications. These factors were prospectively investigated in 173 consecutive patients with proven acute MI, admitted to a city hospital between July and December 1986. Fifty-eight patients (35%) were admitted within three hours of onset of symptoms. Delay in calling a doctor or ambulance was significant: 50% of patients waited for more than two hours after onset of symptoms, 40% more than three hours. Duration of transport to hospital averaged 30 min. Infarct-typical angina of at least 30 min had been present in 143 patients (83%). Atypical symptoms and silent MI was more frequent in the older patients. Diagnostic ST segment elevation of 2 to 3 mm on admission was present in 59 (34%) patients. After consideration of contraindications, present in 120 patients with altogether 165 potential factors, thrombolytic treatment was possible in only seven (4%) of those with the greater ST elevations within three hours after onset of symptoms and 13 (7.5%) within six hours. The most frequent contraindications were age (over 75 years), hypotension, re-infarction at the same site, intramuscular injections (unspecified drugs) within the preceding seven days, or resuscitation with cardiac massage before admission.