Ethical issues in neurocritical care.

Medicine has always tried to push the limits of life. The technological and scientific progress made in resuscitation now makes it possible to keep patients who are more and more severely affected alive, by compensating for organ failure. The management of the brain-damaged patient poses specific ethical problems in intensive care. Most in-hospital deaths of patients with severe acute brain injury occur after a decision to withhold or withdraw life-sustaining treatments. In these patients, a problem is the difficulty in predicting outcome at an early stage. Our reasoning in the management of brain-damaged patients in the intensive care is based on the four main principles of medical ethics: autonomy, beneficence, non-maleficence and distributive justice. In the case of a patient suffering from cerebral palsy, consent is most often impossible to obtain. The respect of this autonomy, can be done by means of advance directives or testimonies of the support person and family. Non-malficence in the resuscitated brain-damaged patient consists of avoiding unreasonable obstinacy. Medical futility means that the proposed therapy should not be performed because available data show that it will not improve the patient's medical condition. A determination of medical futility can be made either in the presence of a vanishingly small probability of physiological effect or an exceedingly poor quality of outcome. However, a distinction must be made between loss of autonomy and unreasonable obstinacy. French law specifies that the physician must use collegial procedure in situations that may concern a brain-damaged patient. In terms of ethical decision-making, the concept of "window of opportunity" is often mentioned. The temporal approach taken is the guarantee of an absence of "a rush". It is important for the health care team and the family to share the progress of the treatment so that everyone understands the evolution of what is happening and the risks taken for the patient. The resuscitation of the brain-damaged patient poses specific and difficult ethical problems. One of the challenges is to be able to assume our decisions, understand them and defend them. It is also to maintain the coherence of our actions and the cohesion of our teams necessary for the good care of our patients.

Antifungal therapy for patients with proven or suspected Candida peritonitis: Amarcand2, a prospective cohort study in French intensive care units.

OBJECTIVE: The clinical characteristics and prognosis of patients treated for Candida peritonitis (CP) were compared according to the type of systemic antifungal therapy (SAT), empiric (EAF) or targeted (TAF) therapies, and the final diagnosis of infection. METHODS: Patients in intensive care units (ICU) treated for CP were selected among the AmarCAND2 cohort, to compare patients receiving EAF for unconfirmed suspicion of CP (EAF/nonCP), to those with suspected secondarily confirmed CP (EAF/CP), or with primarily proven CP receiving TAF. RESULTS: In all, 279 patients were evaluated (43.4% EAF/nonCP, 29.7% EAF/CP and 25.8% TAF patients). At SAT initiation, the severity of illness was similar among EAF/nonCP and EAF/CP patients, lower among TAF patients (median Simplified Acute Physiology Score II (SAPS II) 49 and 51 versus 35, respectively; p 0.001). Candida albicans was involved in 67%, Candida glabrata in 15.6%. All strains were susceptible to echinocandin; 84% to fluconazole. Echinocandin was administered to 51.2% EAF/nonCP, 49% EAF/CP and 40% TAF patients. At day 28, 72%, 76% and 75% of EAF/nonCP, EAF/CP and TAF patients, respectively, were alive. An increased mortality was observed in patients with a Sequential Organ Failure Assessment (SOFA) score <7 if SAT was delayed by ≥6 days (p 0.04). Healthcare-associated CP (OR 3.82, 95% CI 1.52-9.64, p 0.004), SOFA ≥8 at ICU admission (OR 2.61, 95% CI 1.08-6.34; p 0.03), and SAPS II ≥45 at SAT initiation (OR 5.08, 95% CI 1.04-12.67; p 0.001) impacted the 28-day mortality. CONCLUSIONS: In summary, only 56.6% of ICU patients receiving SAT had CP. Most strains were susceptible to SAT. A similar 28-day mortality rate was observed among groups; the late administration of SAT significantly worsened the prognosis of patients with less severe CP.

Difficult intubation in obese patients: incidence, risk factors, and complications in the operating theatre and in intensive care units.

BACKGROUND: Intubation procedure in obese patients is a challenging issue both in the intensive care unit (ICU) and in the operating theatre (OT). The objectives of the study were (i) to compare the incidence of difficult intubation and (ii) its related complications in obese patients admitted to ICU and OT. METHODS: We conducted a multicentre prospective observational cohort study in ICU and OT in obese (BMI≥30 kg m(-2)) patients. The primary endpoint was the incidence of difficult intubation. Secondary endpoints were the risk factors for difficult intubation, the use of difficult airway management techniques, and severe life-threatening complications related to intubation (death, cardiac arrest, severe hypoxaemia, severe cardiovascular collapse). RESULTS: In cohorts of 1400 and 11 035 consecutive patients intubated in ICU and in the OT, 282 (20%) and 2103 (19%) were obese. In obese patients, the incidence of difficult intubation was twice more frequent in ICU than in the OT (16.3% vs 8.2%, P<0.01). In both cohorts, risk factors for difficult intubation were Mallampati score III/IV, obstructive sleep apnoea syndrome, and reduced mobility of cervical spine, while limited mouth opening, severe hypoxaemia, and coma appeared only in ICU. Specific difficult airway management techniques were used in 66 (36%) cases of difficult intubation in obese patients in the OT and in 10 (22%) cases in ICU (P=0.04). Severe life-threatening complications were significantly more frequent in ICU than in the OT (41.1% vs 1.9%, relative risk 21.6, 95% confidence interval 15.4-30.3, P<0.01). CONCLUSIONS: In obese patients, the incidence of difficult intubation was twice more frequent in ICU than in the OT and severe life-threatening complications related to intubation occurred 20-fold more often in ICU. CLINICAL TRIAL REGISTRATION: Current controlled trials. Identifier: NCT01532063.

[Anaesthetic management of brain-dead for organ donation: impact on delayed graft function after kidney transplantation]. / Pratiques anesthésiques pour prélèvement d'organes chez le sujet en mort encéphalique et pronostic du greffon rénal.

BACKGROUND: The aim of this study was to report current anaesthetic management brain-dead organ donors and to assess its impact on delayed kidney graft function (DGF). METHODS: To achieve this retrospective multicenter study, brain-dead patient records were analysed for the years 2005 to 2007. Expanded donor criteria, length of stay in ICU, duration of brain death, respect of recommended cold ischemia time, preoperative and intraoperative management, type of anaesthesia, hemodynamic and respiratory parameters during organ retrieval, and impact of anaesthesia on DGF were analysed. RESULTS: One hundred and forty-nine out of 165 files were available. Sixty-two percent of donors received anaesthetic drugs. There were no differences in demographic characteristics between the anaesthesia group (group A) and the no-anaesthesia group (group NA). In group NA, the mean arterial pressure (MAP)>65 mm Hg was more frequent (53% vs. 29%, P<0.01), but did not differ for maximal MAP. In group A, maximal heart rate was higher (120 vs. 105b/min, P=0.02) and donors received significantly more colloids (P<0.01). Independent risk factors of DGF included absence of hydroxyethyl starch infusion during the preoperative period and mechanical ventilation without PEEP. CONCLUSION: During organ retrieval, 62% of organ donors received anaesthetic drugs. Use of anaesthesia lead to lower MAP requiring more fluid challenge with colloids but did not influence the DGF.

[Causes of early mortality after liver transplantation: a twenty-years single centre experience]. / Mortalité trois mois après transplantation hépatique : étude monocentrique sur une période de vingt ans.

OBJECTIVE: To define the causes of mortality of patients who died within the first three months after a liver transplantation. TYPE OF STUDY: Retrospective, observational, and single centre study. PATIENTS AND METHODS: Between March 1989 and July 2010, all patients who died within three months after a liver transplantation were included. Demographic characteristics, preoperative and peroperative data, donor characteristics, postoperative complications and causes of mortality were collected. RESULTS: Among the 788 performed liver transplantations, 76 patients died in intensive care unit (11%). The main indications of liver transplantation were alcoholic cirrhosis (30%), hepatitis C (28%), hepatocarcinoma (15%), primitive or secondary biliary cirrhosis (10%). Fifty percent of the patients were categorized as Child C. The main causes of death were non-function or dysfunction with retransplantation contra-indication graft (18%), sepsis (18%), neurological complications (12%), hemorrhagic shock (13%), (9%), multiorgan failures (5%), cardiac complications (6%). CONCLUSION: In this study, the main causes of mortality were infectious, neurological and hemorrhagic. These results emphasize the necessity for better control of sepsis, haemorrhage and immunosupressors.

[Severe and acute pancreatitis admitted in intensive care: a prospective epidemiological multiple centre study using CClin network database]. / Épidémiologie, pronostic et complications infectieuses nosocomiales des pancréatites aiguës graves en réanimation: étude prospective multicentrique à partir de la base de données CClin Sud-Est.

OBJECTIVES: To describe the demographic characteristics, incidence of extra-abdominal hospital-acquired infections and outcome of patients admitted to intensive care unit (ICU) with severe acute pancreatitis. STUDY DESIGN: A retrospective, observational multiple center (65 centers) analysis of prospectively acquired data. PATIENTS AND METHODS: During 2 years, all consecutive admitted patients to ICU for severe acute pancreatitis in the centers participating in the nosocomial infections surveillance network CClin Sud-Est were included. Patients whose ICU stay was less than 48 hours were not included. Demographic characteristics, extra-abdominal hospital-acquired infections and clinical course were described. RESULTS: During the study period, 510 patients were included which represented 2 % of patients with a length of stay longer than 48 hours in the 65 participating ICUs. The global attack rate of extra-abdominal hospital-acquired infections (pneumonia, bacteremia, urinary tract or central venous catheter infection) was 23 % in overall patients and it was 33 % in the 294 mechanically ventilated patients. ICU mortality was 20 % in overall patients and it was 34 % in mechanically ventilated patients. CONCLUSION: Severe acute pancreatitis represents 2 % of ICU stay longer than 48 hours. Its clinical course is frequently complicated by hospital-acquired infections and is associated with an high ICU mortality rate. This epidemiological observational study may be used for calculating sample size for future multicenter interventional therapeutic studies.

[Antifungal treatments of candidemia in non-neutropenic patients: evaluation of practice in intensive care units]. / Traitements antifongiques des candidémies chez les patients non neutropéniques : évaluation des pratiques en réanimation.

OBJECTIVE: The authors had for objective to assess systemic antifungal treatment for candidemia in non-neutropenic patients, in intensive care units (ICU), and compare the results with French 2004 recommendations. STUDY DESIGN: A retrospective multicenter study (nine ICU in two teaching hospitals) was made. PATIENTS AND METHOD: Thirty-eight non-neutropenic patients with at least one positive blood culture for Candida who had received systemic antifungal treatment were included between May 2004 and September 2007. RESULTS: Thirty-nine cases of candidemia were analyzed. The median age was 54.5 (21-80), the median SAPS II score at admission was 44 (20-79), the median duration of stay in ICU was 22.5 days (2-82), and the death rate was 45%. Candida albicans was identified in 69% of the cases. Eight percent of Candida sp. isolates were resistant or susceptible dose-dependent (S-DD) to fluconazole. Before identification, fluconazole, caspofungin, voriconazole, and amphotericin B were used in 74%, 15%, 5%, and 5% of cases respectively. After identification and antifungal susceptibility determination, fluconazole was used in 68% of cases, caspofungin in 24% of cases, any formulation of amphotericin B in 6% of cases, voriconazole in 3% of cases. The French recommendations were applied in 71% of cases before identification and in 68% of cases after identification and antifungal susceptibility determination. CONCLUSION: The main causes of non-compliance to recommendations were the use of fluconazole in patients previously exposed to azole agents, the use of caspofungin in hemodynamically unstable patients, and the absence of therapeutic desescalade.

[Tigecycline for treatment of severe infections in intensive care: a drug use evaluation]. / Expérience de l'utilisation de la tigécycline dans le traitement des infections sévères en réanimation: une étude pilote.

OBJECTIVES: To report our experience of tigecycline use in a medical and surgical intensive care unit. To describe its prescription, microbiology findings, tolerance and efficacy. STUDY DESIGN: Prospective, observational, single center study. PATIENTS AND METHODS: All consecutive patients treated with tigecycline were included. Demography, indication of treatment, bacteriology before, during and in the month after treatment and ICU mortality were collected. The main endpoints were clinical and microbiological efficacy and tolerance. RESULTS: Twenty-four patients were included. In half of the cases, tigecycline was prescribed in monotherapy for a complicated intra-abdominal infection. Overall tolerance of tigecycline was good. Clinical and microbiological cure was obtained in six cases, not obtained in nine, indeterminate in six cases and not evaluable in the three cases of prophylaxis. During the treatment, four bacteria commonly sensitives were shown to be resistant to tigecycline. CONCLUSION: Our pilot study on 24 patients suggests that tigecycline is well tolerated in critically ill patients. Clinical cure in severe infections was compromised in nine patients essentially because of resistant pathogens suggesting its prescription on antibiogram. However, the impact of association or the increasing doses in severe critically ill patients should be evaluated.

[Ventilator-associated pneumonia: follow the guidelines!]. / Pneumonies acquises sous ventilation mécanique: suivez les recommandations!

OBJECTIVES: To compare the clinical outcomes and the causative pathogens of early-onset and late-onset ventilator-associated pneumonia (VAP) diagnosed by bronchoalveolar lavage (BAL). STUDY DESIGN: Prospective, observational, epidemiological study. PATIENTS AND METHODS: During a 7-years period, all first episodes of VAP were prospectively included. Diagnosis was confirmed by a BAL with a threshold of 10(4) cfu/ml. Late-onset pneumonia was defined if occurred after the seventh day after mechanical ventilation. RESULTS: One hundred and thirteen VAP were studied. Fifty were early-onsets and 63 late-onsets. Thirty-four per cent of early-onset VAP and 73% of late-onset VAP were due to potential multiresistants pathogens. Pseudomonas aeruginosa was the most commonly isolated bacteria both in early-onset and late-onset VAP (16 and 39% respectively). Morbidity and mortality (29 vs 29%, ns) were not statically different between the two groups (early-onset and late-onset VAP). CONCLUSION: In our study, both early-onset and late-onset VAP were mainly caused by potentially multiresistants bacteria, most commonly Gram negative bacilli. Even for early VAP, clinicians should be aware about all risk factors for potentially multiresistants pathogens and not only the delay of onset of the VAP episode.

[Catheter-related infections: how to reduce the risk?]. / Infections sur cathéter: comment réduire l'exposition au risque ?

Subcutaneous tunnelling of short-term catheters and the choice of site of catheter insertion are the two factors which influence the risk of catheter-related infection. Catheters inserted into a femoral vein have been associated with a higher risk of infection than those inserted into a subclavian vein. However, a meta-analysis comparing the internal jugular and subclavian sites did not report any difference. Regarding tunnelling, two randomized studies showed a benefit in terms of infection rates for the jugular and femoral sites when the blood sampling was not performed via the catheters. For the subclavian site tunnelling does not seem to bring any advantage compared to conventional insertion.

[Phoning study about postoperative practice and application of non-invasive ventilation]. / Enquête téléphonique sur la pratique postopératoire de la ventilation non invasive et ses modalités d'application.

OBJECTIVES: Incidence and management of positive pressure non-invasive ventilation (NIV) in intensive care unit (ICU) in the postoperative period. STUDY DESIGN: Phoning study performed on September 2001 in 60 ICU of south of France (public: 47, private: 13, medical: 11, surgical: 20, medical-surgical: 29), which were randomized from a national list. RESULTS: NIV was used currently on 55% and casually on 35% of the units. Ten percent of ICU, which never use NIV, were surgical on 83% with a lower number of bed (7 +/- 3 vs. 12 +/- 5). The most often humidification device used was a Heat and Moisture Exchanger (HME) (52%), a Heated Humidifier (HH) (26%), either (4%) and none device (19%). ICU that never used a humidification device used a home ventilator in 30%. Ventilators used were more often heavy ICU ventilators (80%) with a facial mask (89%). NIV was performed exclusively by physicians in 15% of cases and in collaboration after the first application in 71% of cases. Sixty-nine % of intensivists used NIV as a first choice for the treatment of acute postoperative respiratory failure and 54% of intensivists for the treatment of postoperative atelectasis. CONCLUSION: Use of NIV increases in ICU, particularly in surgical units. Practices are different between ICU. An HME is the most frequently humidification device used.

Haemodynamic effects of an angiotensin-converting enzyme inhibitor and angiotensin receptor antagonist during hypovolaemia in the anaesthetized pig.

BACKGROUND: Renin-angiotensin system antagonists, either angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor (AT(1)) antagonists, may interfere with regulation of arterial pressure during anaesthesia. This study aimed to compare the haemodynamic profile of anaesthetized pigs, which were subjected to haemorrhage in the presence of the ACE inhibitor enalaprilat or the AT(1) antagonist valsartan. METHODS: Thirty-six pigs were assigned randomly to placebo, enalaprilat or valsartan groups. After a 30-min period of stabilization following anaesthesia and injection of the study drug, the animals were bled in two equal steps of 20% of their estimated blood volume (20% BV and 40% BV). RESULTS: After bleeding of 20% BV, the mean arterial pressure (MAP) decreased significantly but similarly in each group (20-25%) but the placebo and the enalaprilat groups had a significant decrease in cardiac index (CI, 22% and 16%, respectively) without significant change in systemic vascular resistance (SVR). Conversely, in the valsartan group, SVR decreased significantly (23%, P<0.02 vs other groups) without significant change in CI (-4%). After bleeding of 40% BV, the CI decreased significantly compared with 20% BV in the three groups (19% in the placebo and enalaprilat groups, 14% in the valsartan group) but the MAP decreased significantly in the enalaprilat group only (23%). The SVR increased significantly in the placebo group (P<0.01 vs each of the other groups), but there were no differences in the change in SVR between the other groups. CONCLUSION: Blockade of the renin-angiotensin system by either enalaprilat or valsartan leads to a similar decrease in arterial pressure during anaesthesia and haemorrhage but the haemodynamic profiles are quite different.

[Cerebral arterial air embolism associated with pneumothorax in a patient with pressure support ventilation]. / Embolie gazeuse cérébrale consécutive à un pneumothorax chez une patiente en aide inspiratoire.

A 20-year-old woman was admitted to the ICU following a road traffic accident. She had a periorbital haematoma with a normal cerebral state on CT-scan, intrahepatic and intrasplenic haematomas and several fractures of the limb that were fixed on day 3. Twenty-four hours later, she developed a cough with symptoms of decerebration The head CT-scan showed diffuse pneumocephalus suitable with cerebral air embolism and the chest X ray a right tension pneumothorax. A chest tube was inserted. Despite the lack of hyperbaric oxygen therapy the patient recovered fully. The pneumocephalus disappeared totally after 48 hours. Seven days later, CT-scan of the head with coronal slides showed an orbital floor fracture associated with an intra-orbital aerocele.

Alcoholic cirrhosis is a good indication for liver transplantation, even for cases of recidivism.

BACKGROUND/AIMS: Alcoholic cirrhosis remains a controversial indication for liver transplantation, mainly because of ethical considerations related to the shortage of donor livers. The aim of this study was to review experience to date, focusing on survival rates and complications, and the effect of alcohol relapse on outcome and alterations in marital and socioprofessional status. METHODS: The results for 53 patients transplanted for alcoholic cirrhosis between 1989 and 1994 were compared with those for 48 patients transplanted for non-alcoholic liver disease. The following variables were analysed: survival, rejection, infection, cancer, retransplantation, employment and marital status, alcoholic recurrence. The same variables were compared between alcohol relapsers and non-relapsers. RESULTS: Recovery of employment was the only significantly different variable between alcoholic (30%) and non-alcoholic patients (60%). Two factors influenced survival in the absence of alcohol recidivism: age and abstinence before transplantation. For all other variables, there were no differences between alcoholic and non-alcoholic patients, and, within the alcoholic group, between relapsers and non-relapsers. The recidivism rate was 32%. CONCLUSION: The data indicate that liver transplantation is justified for alcoholic cirrhosis, even in cases of recidivism, which did no affect survival and compliance with the immunosuppressive regimen. These good results should help in educating the general population about alcoholic disease.

Changes in occlusion pressure (P0.1) and breathing pattern during pressure support ventilation.

BACKGROUND: The purpose of this study was to investigate changes in breathing pattern, neuromuscular drive (P0.1), and activity of the sternocleidomastoid muscles (SCM) during a gradual reduction in pressure support ventilation (PSV) in patients being weaned off controlled mechanical ventilation. METHODS: Eight non-COPD patients recovering from acute respiratory failure were included in this prospective interventional study. All patients were unable to tolerate discontinuation from mechanical ventilation. Each patient was evaluated during a period of spontaneous breathing and during PSV. Four successive levels of PSV were assessed in the following order: 20 cm H2O (PS20), 15 cm H2O (PS15), 10 cm H2O (PS10), and 5 cm H2O (PS5). RESULTS: When pressure support was reduced from PS20 to PS10 the respiratory rate (f) and the rapid shallow breathing index (f/VT) significantly increased and tidal volume (VT) significantly decreased. These parameters did not vary when pressure support was reduced from PS10 to PS5. Conversely, P0.1 varied negligibly between PS20 and PS15 but increased significantly at low PSV levels. P0.1 values were always greater than 2.9 cm H2O (4.1 (1.1) cm H2O) when SCM activity was present. When contraction of the SCM muscles reappeared the P0.1 was the only parameter that changed significantly. CONCLUSIONS: In postoperative septic patients the value of P0.1 seems to be more useful than breathing pattern parameters for setting the optimal level of pressure assistance during PSV.

Staphylococcus aureus nasal carriage in 104 cirrhotic and control patients. A prospective study.

BACKGROUND/AIMS: Bacterial infections, specially Staphylococcus aureus (S. aureus) septicemia, remain a leading cause of death following liver transplantation. It has been demonstrated that nasal carriage of S. aureus is associated with invasive infections in patients undergoing hemodialysis and could be decreased by use of antibiotic nasal ointment. However, in cirrhotic patients, the frequency of nasal carriage is unknown. The aims of this study were to determine the prevalence of S. aureus nasal carriage in cirrhotic patients and to assess nosocomial contamination. METHODS: One hundred and four patients were included in a prospective study, 52 cirrhotic and 52 control (hospitalized patients without cirrhosis or disease which might increase the rate of nasal carriage of S. aureus). On admission and after a few days of hospitalization, nasal specimens from each anterior naris were obtained for culture. S. aureus was identified by the gram strain, positive catalase and coagulase reactions; antibiotic susceptibility was determined using a disk-diffusion test. RESULTS: Both groups were similar with regard to age and sex. The prevalence of nasal colonization on hospital admission was 56% in cirrhotic patients and 13% in control patients (p = 0.001). After an average of 4 days, 42% of cirrhotics and 8% of control patients were colonized (p = 0.001), without any nosocomial contamination. Three strains out of 29 were oxacillin-resistant in cirrhotic patients, and none in controls (p>0.05). There was no statistical difference in carriage rate according to sex, age, cause of cirrhosis and Child-Pugh score. Previous hospitalization (OR, 6.3; 95% CI, 2.3 to 19.9; p = 0.0006) and cirrhosis (OR, 4.4; 95% CI, 1.5 to 13.4; p = 0.0048) were independent predictors of colonization. CONCLUSION: Cirrhotic patients had a higher S. aureus nasal carriage rate than control subjects. Previous hospitalization and cirrhosis diagnosis were correlated to nasal colonization. Further studies are necessary to determine if nasal decontamination could reduce S. aureus infections after liver transplantation.

Tension-time index of inspiratory muscles in COPD patients: role of airway obstruction.

Inspiratory muscle function has been shown to be related to general muscle weakness, weight loss, blood gas tensions, airway obstruction and hyperinflation. The aim of this study was to define (1) the factor that is the main determinant of the tension-time index of the inspiratory muscles (TTmus), and which this increases the risk of inspiratory muscle fatigue; and (2) whether a breathing strategy is adopted to avoid inspiratory muscle fatigue. Twenty-seven normal volunteers and 35 stable COPD outpatients (FEV1% predicted, range: 21-89%; and FRC/TLC, range: 49-77%) were studied. The TTmus was determined as follows: TTmus = PI/PImax.TI/Ttot, where Pi is the mean inspiratory pressure calculated from the mouth occlusion pressure (P0.1), PImax is the maximal inspiratory pressure, TI is the inspiratory time, and Ttot is the total time of the breathing cycle. COPD patients showed significantly lower PImax and higher P0.1, PI, PI/PImax, and TTmus than normal subjects. No patient had a TTmus value higher than the inspiratory muscle fatigue threshold of 0.33. The FEV1 was significantly correlated with TTmus and all its components in the patients. The FRC/TLC was also correlated with all components except PI. Body weight was only correlated with PImax. In a forward and backward stepwise regression analysis, FEV1 appeared to be the only significant factor explaining the variance of log (PI/PImax) and log (TTmus), whereas FRC/TLC was the principal determinant of PImax. In COPD patients, a non-linear relationship was found between TI and P0.1. A negative linear relationship was found between TI/Ttot and PI/PImax. In conclusion, although hyperinflation predominantly affected inspiratory muscle strength in a group of stable COPD patients with a wide range of severity, airway obstruction was the principal factor determining the magnitude of TTmus. In addition, in order to remain below the inspiratory muscle fatigue threshold, as the severity of airway obstruction increased, patients adopted a breathing strategy characterized by decreased TI/Ttot as inspiratory pressure demand increased.

Activated sub-populations of lymphocytes and natural killer cells in normal liver and liver grafts before transplantation.

AIMS/BACKGROUND: The anatomic structure of the liver suggests that it is a place of intense trafficking between intra-hepatic and peripheral blood compartment leukocytes. Furthermore, the liver contains a large number of passenger leukocytes that may play a role in the appearance of donor-type microchimerism after transplantation. In this study, we aimed to define the principal lymphocyte sub-populations contained in donor peripheral blood and liver grafts and in normal liver removed during minimally invasive surgery. METHODS: Liver biopsies were taken at the time of vascular clampage during liver extraction from donors in a brain dead state (GI: n=14). Normal liver biopsies were removed during minimaly invasive surgery (GII: n= 10). RESULTS: We observed evidence of the presence of lymphocytic activation associated with the two major CD8+ lymphocyte and natural killer (NK) cell populations in the two groups, with a significant increase in TCRgammadelta-bearing lymphocyte receptors between normal liver and the liver graft. CONCLUSIONS: The presence of activated leukocytes in the graft could have a fundamental role in induction of peripheral tolerance. This activation could be the result of a basic immunological response linked to the interaction of T cells and NK cells, and of secondary activation due to stress and the conditions necessary for organ removal from donors in a brain dead state.