Mycophenolatemofetil in non-renal systemiclupuserythematosusmanifestations

Trabalho Final do Curso de Mestrado Integrado em Medicina, Faculdade de Medicina, Universidade de Lisboa, 2014

Décès pendant une simulation médicale : perspectives des apprenants et impacts sur le stress et la performance des réanimateurs

L’acceptabilité d’un décès lors d’une simulation médicale reste débattue mais il existe peu de données sur la perspective des apprenants. Des médecins résidents ont effectué une pratique de code et ont rempli un questionnaire pré et post-simulation. Ils ont été exposés à deux scénarios où un bébé naissait sans signe de vie: 1. Nouveau-né ne répondant pas aux manœuvres de réanimation (DCD); 2. Nouveau-né s’améliorant avec une réanimation adéquate (REA). Les performances étaient évaluées à l’aide de la grille standardisée du Programme de Réanimation Néonatale. Le stress objectif (cortisol salivaire) et subjectif a été mesuré après le code. La rétroaction («feedback»), individuelle et en groupe, fut analysée à l’aide de méthodologies qualitatives. 59/62 apprenants ont répondu au questionnaire et 42 ont participé à la simulation. Tous les résidents trouvent les simulations bénéfiques et souhaitent y être exposés davantage. Le type et l’ordre des scénarios n’ont pas eu d’impact sur la performance. Un seul résident a interrompu les manœuvres de réanimation après 10 minutes d’asystolie, tel que recommandé, et 31% ont poursuivi après 20 minutes. Les participants trouvaient le scénario DCD plus stressant. Les niveaux de cortisol salivaire ont augmenté après les simulations (p<0.001) et ce, pour les deux scénarios. Cette augmentation était indépendante du scénario (p=0.06) et n’était pas associée à la performance. Les réponses à la question « Comment a été votre expérience? », ont permis d’identifier deux thèmes: 1. Le mannequin ne meurt pas en simulation médicale; 2. Le décès lors de la simulation signifie une réanimation inadéquate. Le décès lors d’une pratique de code est stressant, mais n’interfère pas avec la performance des soignants. Les apprenants trouvent cet exercice acceptable et bénéfique à leur pratique future.

NT-proBNP in patients with out-of-hospital cardiac arrest: Results from the FINNRESUSCI Study

AIM To assess whether the established cardiovascular biomarker N-terminal pro-B-type natriuretic peptide (NT-proBNP) provides prognostic information in patients with out-of-hospital cardiac arrest due to ventricular tachycardia or fibrillation (OHCA-VT/VF). METHODS We measured NT-proBNP levels in 155 patients with OHCA-VT/VF enrolled into a prospective multicenter observational study in 21 ICUs in Finland. Blood samples were drawn <6h of OHCA-VT/VF and later after 24h, 48h, and 96h. The end-points were mortality and neurological outcome classified according to Cerebral Performance Category (CPC) after one year. NT-proBNP levels were compared to high-sensitivity troponin T (hs-TnT) levels and established risk scores. RESULTS NT-proBNP levels were higher in non-survivors compared to survivors on study inclusion (median 1003 [quartile (Q) 1-3 502-2457] vs. 527 [179-1284]ng/L, p=0.001) and after 24h (1913 [1012-4573] vs. 1080 [519-2210]ng/L, p<0.001). NT-proBNP levels increased from baseline to 96h after ICU admission (p<0.001). NT-proBNP levels were significantly correlated to hs-TnT levels after 24h (rho=0.27, p=0.001), but not to hs-TnT levels on study inclusion (rho=0.05, p=0.67). NT-proBNP levels at all time points were associated with clinical outcome, but only NT-proBNP levels after 24h predicted mortality and poor neurological outcome, defined as CPC 3-5, in models that adjusted for SAPS II and SOFA scores. hs-TnT levels did not add prognostic information to NT-proBNP measurements alone. CONCLUSION NT-proBNP levels at 24h improved risk assessment for poor outcome after one year on top of established risk indices, while hs-TnT measurements did not further add to risk prediction.

Mean arterial pressure and vasopressor load after out-of-hospital cardiac arrest: Associations with one-year neurologic outcome

THE AIM OF THE STUDY There are limited data on blood pressure targets and vasopressor use following cardiac arrest. We hypothesized that hypotension and high vasopressor load are associated with poor neurological outcome following out-of-hospital cardiac arrest (OHCA). METHODS We included 412 patients with OHCA included in FINNRESUSCI study conducted between 2010 and 2011. Hemodynamic data and vasopressor doses were collected electronically in one, two or five minute intervals. We evaluated thresholds for time-weighted (TW) mean arterial pressure (MAP) and outcome by receiver operating characteristic (ROC) curve analysis, and used multivariable analysis adjusting for co-morbidities, factors at resuscitation, an illness severity score, TW MAP and total vasopressor load (VL) to test associations with one-year neurologic outcome, dichotomized into either good (1-2) or poor (3-5) according to the cerebral performance category scale. RESULTS Of 412 patients, 169 patients had good and 243 patients had poor one-year outcomes. The lowest MAP during the first six hours was 58 (inter-quartile range [IQR] 56-61) mmHg in those with a poor outcome and 61 (59-63) mmHg in those with a good outcome (p<0.01), and lowest MAP was independently associated with poor outcome (OR 1.02 per mmHg, 95% CI 1.00-1.04, p=0.03). During the first 48h the median (IQR) of the TW mean MAP was 80 (78-82) mmHg in patients with poor, and 82 (81-83) mmHg in those with good outcomes (p=0.03) but in multivariable analysis TWA MAP was not associated with outcome. Vasopressor load did not predict one-year neurologic outcome. CONCLUSIONS Hypotension occurring during the first six hours after cardiac arrest is an independent predictor of poor one-year neurologic outcome. High vasopressor load was not associated with poor outcome and further randomized trials are needed to define optimal MAP targets in OHCA patients.

Elevated plasma levels of human urotensin-II immunoreactivity in congestive heart failure

Human urotensin-II (hU-II) is the most potent endogenous cardiostimulant identified to date. We therefore determined whether hU-II has a possible pathological role by investigating its levels in patients with congestive heart failure (CHF). Blood samples were obtained from the aortic root, femoral artery, femoral vein, and pulmonary artery from CHF patients undergoing cardiac catheterization and the aortic root from patients undergoing investigative angiography for chest pain who were not in heart failure. Immunoreactive hU-II (hU-II-ir) levels were determined with radioimmunoassay. hU-II-ir was elevated in the aortic root of CHF patients (230.9 +/- 68.7 pg/ml, n = 21; P < 0.001) vs. patients with nonfailing hearts (22.7 +/- 6.1 pg/ml, n = 18). This increase was attributed to cardiopulmonary production of hU-II-ir because levels were lower in the pulmonary artery (38.2 +/- 6.1 pg/ml, n = 21; P < 0.001) than in the aortic root. hU-II-ir was elevated in the aortic root of CHF patients with nonischemic cardiomyopathy (142.1 +/- 51.5 pg/ml, n = 10; P < 0.05) vs. patients with nonfailing hearts without coronary artery disease (27.3 +/- 12.4 pg/ml, n = 7) and CHF patients with ischemic cardiomyopathy (311.6 +/- 120.4 pg/ml, n = 11; P < 0.001) vs. patients with nonfailing hearts and coronary artery disease (19.8 +/- 6.6 pg/ml, n = 11). hU-II-ir was significantly higher in the aortic root than in the pulmonary artery and femoral vein, with a nonsignificant trend for higher levels in the aortic root than in the femoral artery. The findings indicated that hU-II-ir is elevated in the aortic root of CHF patients and that hU-II-ir is cleared at least in part from the microcirculation.

Crystalloid strong ion difference determines metabolic acid-base change during acute normovolaemic haemodilution

Objective. To study the acid-base effects of crystalloid strong ion difference (SID) during haemodilution. Design. Prospective in vivo study. Setting. University laboratory. Subjects. Anaesthetised, mechanically ventilated Sprague-Dawley rats. Interventions. Rats were studied in seven groups of three. Each group underwent normovolaemic haemodilution with one of seven crystalloids, with SID values from 0 to 40 mEq/l. Six exchanges of 9 ml crystalloid for 3 ml blood were performed. Measurements and main results. [Hb] fell from 142+/-17 to 44+/-10 g/l (p

Quality assurance of paediatric cardiac surgery: A prospective 6-year analysis

Objective: To audit effective quality assurance methods to monitor outcomes following paediatric cardiac surgery at a single institution. Methods: All patients undergoing cardiac surgery from January 1996 to December 2001 were enrolled prospectively. Patients were stratified by complexity of surgical procedure into four groups, with Category 4 being the most complex procedure. Outcome measures included death, length of admission and morbidity from complications. Results: A total of 1815 patients underwent 1973 surgical procedures. Of these, 1447 (73.3%) were cardiopulmonary bypass procedures, and 543 (27.5%) were more complex (Category 3 and 4) procedures. Median patient age was 3.5 years (range, 1 day-20 years) and patient weight 15.0 kg (range, 900 g to 90 kg). Sixty-six patients (3.6%) died during the study period. Of the procedures in 1996, 22.7% were classified as complex compared with 29.2% of procedures in 2001. The annual surgical mortality ranged from 1.9-4.7% (P=0.20), and when mortality was adjusted for complexity of surgery, there was no significant yearly variation in the mortality rate (P=0.57). Analysis of individual surgeon's results showed no significant difference in the mortality rate by complexity of surgery performed (P=0.90). Mean ventilation times did not change significantly over time (P=0.79). The yearly incidence of significant neurological complications ranged from 0.6% to 4.5% and the incidence of arrhythmias from 4.2% to 8.0%. No difference was detected between the years. Conclusions: Stratifying complexity of surgery proved valuable in monitoring surgical outcomes and detecting differences in performance over time as large subgroups were created for analysis.

Protein losing enteropathy in critically ill adult patients with burns: a preliminary report

Objective: Few data have been published regarding protein losing enteropathy in adult patients with burns. This study characterised the presence of protein-losing enteropathy in adults with burns and examined the relationship between the magnitude of bum size and the severity of protein loss. Methods: Twenty adult patients with burns (BSA 31+/-25%, range 2-80%) were studied. Fluid resuscitation was based on the Parkland's formula. Protein loss into the gastrointestinal tract was measured using faecal alpha(1)-antitrypsin (FA-1-AT) concentrations. Serial measurements of serum protein and albumin concentrations were performed. Results: Fourteen patients demonstrated elevations in FA-1-AT levels. The mean peak FA-1-AT level was 3.6+/-4.2 mg/g dry weight of stool. Two patients demonstrated elevated FA-1-AT excretion 1.5 months and 3 months after the bums. There was a good correlation between burn size and FA-1-AT excretion (R-2=0.40). Conclusions: Protein losing enteropathy was demonstrable in patients with major burns. The magnitude of this phenomenon appears to be proportional to the burns size.

Histopathology and fibrillin-1 distribution in severe early onset Marfan syndrome

Marfan syndrome (MFS) is an autosomal dominant condition which may involve the cardiovascular, ocular, skeletal, and other systems. Mutations causing MFS are found in the FBN1 gene, encoding fibrillin-1, an extracellular matrix protein involved in microfibril formation. In the most severe cases, mutations are generally found in exons 24-32, and children with these mutations usually die in the first years of life, of cardiopulmonary failure. We present clinical, molecular and histopathological studies on a patient with severe early onset MFS. He has a mutation in exon 25 of FBN1, a G > A transition at nucleotide position 3131 that converts the codon TGC, coding for cysteine at position 1044, to TAC, coding for tyrosine (C1044Y). This has resulted in abnormalities of the extracellular matrix and a severe clinical phenotype, although he has survived to the age of 14 years. (c) 2005 Wiley-Liss, Inc.

The effect of positive end-expiratory pressure level on peak expiratory flow during manual hyperinflation

Including positive end-expiratory pressure (PEEP) in the manual resuscitation bag (MRB) may render manual hyperinflation (MHI) ineffective as a secretion maneuver technique in mechanically ventilated patients. In this study we aimed to determine the effect of increased PEEP or decreased compliance on peak expiratory flow rate (PEF) during MHI. A blinded, randomized study was performed on a lung simulator by 10 physiotherapists experienced in MHI and intensive care practice. PEEP levels of 0-15 cm H2O, compliance levels of 0.05 and 0.02 L/cm H2O, and MRB type were randomized. The Mapleson-C MRB generated significantly higher PEF (P < 0.01, d = 2.72) when compared with the Laerdal MRB for all levels of PEEP. In normal compliance (0.05 L/cm H2O) there was a significant decrease in PEF (P < 0.01, d = 1.45) for a PEEP more than 10 cm H2O in the Mapleson-C circuit. The Laerdal MRB at PEEP levels of more than 10 cm H2O did not generate a PEF that is theoretically capable of producing two-phase gas-liquid flow and, consequently, mobilizing pulmonary secretions. If MHI is indicated as a result of mucous plugging, the Mapleson-C MRB may be the most effective method of secretion mobilization.

Applications of transcranial Doppler in the ICU: a review

Objective: Transcranial Doppler (TCD) ultrasonography is a technique that uses a hand-held Doppler transducer (placed on the surface of the cranial skin) to measure the velocity and pulsatility of blood flow within the intracranial and the extracranial arteries. This review critically evaluates the evidence for the use of TCD in the critical care population. Discussion: TCD has been frequently employed for the clinical evaluation of cerebral vasospasm following subarachnoid haemorrhage (SAH). To a lesser degree, TCD has also been used to evaluate cerebral autoregulatory capacity, monitor cerebral circulation during cardiopulmonary bypass and carotid endarterectomies and to diagnose brain death. Technological advances such as M mode, colour Doppler and three-dimensional power Doppler ultrasonography have extended the scope of TCD to include other non-critical care applications including assessment of cerebral emboli, functional TCD and the management of sickle cell disease. Conclusions: Despite publications suggesting concordance between TCD velocity measurements and cerebral blood flow there are few randomized controlled studies demonstrating an improved outcome with the use of TCD monitoring in neurocritical care. Newer developments in this technology include venous Doppler, functional Doppler and use of ultrasound contrast agents.

Assessment of statistical change criteria used to define significant change in neuropsychological test performance following cardiac surgery

Objective: This paper compares four techniques used to assess change in neuropsychological test scores before and after coronary artery bypass graft surgery (CABG), and includes a rationale for the classification of a patient as overall impaired. Methods: A total of 55 patients were tested before and after surgery on the MicroCog neuropsychological test battery. A matched control group underwent the same testing regime to generate test–retest reliabilities and practice effects. Two techniques designed to assess statistical change were used: the Reliable Change Index (RCI), modified for practice, and the Standardised Regression-based (SRB) technique. These were compared against two fixed cutoff techniques (standard deviation and 20% change methods). Results: The incidence of decline across test scores varied markedly depending on which technique was used to describe change. The SRB method identified more patients as declined on most measures. In comparison, the two fixed cutoff techniques displayed relatively reduced sensitivity in the detection of change. Conclusions: Overall change in an individual can be described provided the investigators choose a rational cutoff based on likely spread of scores due to chance. A cutoff value of ≥20% of test scores used provided acceptable probability based on the number of tests commonly encountered. Investigators must also choose a test battery that minimises shared variance among test scores.