Year in review in Intensive Care Medicine, 2008: II. Experimental, acute respiratory failure and ARDS, mechanical ventilation and endotracheal intubation

SCOPUS: re.jinfo:eu-repo/semantics/publishe

Cluster analysis of behavioural and event-related potentials during a contingent negative variation paradigm in remitting-relapsing and benign forms of multiple sclerosis

<p>Abstract</p> <p>Background</p> <p>Event-related potentials (ERPs) may be used as a highly sensitive way of detecting subtle degrees of cognitive dysfunction. On the other hand, impairment of cognitive skills is increasingly recognised as a hallmark of patients suffering from multiple sclerosis (MS). We sought to determine the psychophysiological pattern of information processing among MS patients with the relapsing-remitting form of the disease and low physical disability considered as two subtypes: 'typical relapsing-remitting' (RRMS) and 'benign MS' (BMS). Furthermore, we subjected our data to a cluster analysis to determine whether MS patients and healthy controls could be differentiated in terms of their psychophysiological profile.</p> <p>Methods</p> <p>We investigated MS patients with RRMS and BMS subtypes using event-related potentials (ERPs) acquired in the context of a Posner visual-spatial cueing paradigm. Specifically, our study aimed to assess ERP brain activity in response preparation (contingent negative variation -CNV) and stimuli processing in MS patients. Latency and amplitude of different ERP components (P1, eN1, N1, P2, N2, P3 and late negativity -LN) as well as behavioural responses (reaction time -RT; correct responses -CRs; and number of errors) were analyzed and then subjected to cluster analysis.</p> <p>Results</p> <p>Both MS groups showed delayed behavioural responses and enhanced latency for long-latency ERP components (P2, N2, P3) as well as relatively preserved ERP amplitude, but BMS patients obtained more important performance deficits (lower CRs and higher RTs) and abnormalities related to the latency (N1, P3) and amplitude of ERPs (eCNV, eN1, LN). However, RRMS patients also demonstrated abnormally high amplitudes related to the preparation performance period of CNV (cCNV) and post-processing phase (LN). Cluster analyses revealed that RRMS patients appear to make up a relatively homogeneous group with moderate deficits mainly related to ERP latencies, whereas BMS patients appear to make up a rather more heterogeneous group with more severe information processing and attentional deficits.</p> <p>Conclusions</p> <p>Our findings are suggestive of a slowing of information processing for MS patients that may be a consequence of demyelination and axonal degeneration, which also seems to occur in MS patients that show little or no progression in the physical severity of the disease over time.</p

Modulation of regional nitric oxide metabolism: blood glucose control or insulin?

OBJECTIVE: Tight glycaemic control by intensive insulin therapy (IIT) reduces morbidity and mortality in critically ill patients. As potential mechanisms contributing to the clinical benefits we hypothesized that glycaemic control affects regional nitric oxide (NO) bioavailability by changing NO synthases (NOS) activity, NOS transcription, NOS substrate availability or the endogenous NOS inhibitor asymmetric dimethylarginine (ADMA) levels. DESIGN: Prospective, randomized experimental study. SETTING: University medical laboratory. INTERVENTIONS: In a rabbit model of prolonged critical illness we assessed the relative impact of maintaining normal insulin/normoglycaemia (n=8), high insulin/normoglycaemia (n=8), normal insulin/hyperglycaemia (n=9) and high insulin/hyperglycaemia (n=8) plasma levels over 7 days on activity and gene expression of endothelial and inducible NOS isoforms in muscle, liver and aorta biopsies, and on plasma levels of NO, arginine and ADMA. MEASUREMENTS AND RESULTS: Compared with normoglycaemic groups, both hyperglycaemic groups revealed 53% higher day-3 NO plasma levels (p&lt;0.05), 40% lower NOS activity in muscle (p&lt;0.01) and 35% lower endothelium-mediated relaxation of aortic rings (p&lt;0.01), 515% higher gene expression of iNOS in muscle (p&lt;0.01) and 99% higher eNOS gene expression in aorta (p&lt;0.01). Only the hyperglycaemic/hyperinsulinaemic group showed lower arginine plasma levels (53% lower, p&lt;0.0001). Compared with healthy controls, normoglycaemic animals revealed 33% lower ADMA levels (p&lt;0.05). CONCLUSIONS: In this animal model of prolonged critical illness, maintaining normoglycaemia, and not glycaemia-independent actions of insulin, prevented excessive systemic NO release on day 3 and appeared to preserve local endothelial function. Factors contributing to this finding may comprise direct endothelial cell damage, direct effects on the enzyme activity, decreased substrate availability or less NO-induced inhibition.status: publishe

The effect of rosiglitazone on asymmetric dimethylarginine (ADMA) in critically ill patients

0.001). Both ADMA (B = 3.5; 95% Cl: 0.5-6.5; p = 0.023) and SDMA (B = 1.7; 95% Cl: 0.7-2.7; p = 0.001) were independently related to SOFA scores. Overall, rosiglitazone treatment had no effect on ADMA levels, which only significantly differed between the rosiglitazone and control groups at day 7 (p = 0.028). The SOFA score in the rosiglitazone group was lower compared to the control group but the difference was only statistically significant at day 10 (p = 0.01). In conclusion, in critically ill patients plasma ADMA levels were elevated and associated with the extent of multiple organ failure, but no significant ADMA-lowering effect of the PPAR-gamma agonist rosiglitazone was observed. (C) 2009 Elsevier Ltd. All rights reserve

Einfluss der initialen Behandlungsqualität und der Inzidenz kritischer Ereignisse auf die Lebensqualität von Überlebenden des schweren akuten Lungenversagens (ARDS) - eine Deutschland-weite prospektive multizentrische Observationsstudie

Background: Initial treatment (ventilator settings, rescue therapy, supportive measures), and prevention of critical events improve survival in ARDS patients, but little data exists on its effect on health-related quality of life (HRQOL) and return to work (RtW) in survivors. We analyzed the association of the intensity of treatment at ARDS onset and the incidence of critical events on HRQOL and RtW a year after ICU discharge.Methods: In a prospective multi-centre cohort study, the intensity of treatment and the incidence of critical events were determined at 61 ICUs in Germany. At 3, 6, and 12 months, 396 survivors reported their HRQOL (Short-Form 12) and RtW. The parameters of the intensity of acute management (lung protective ventilation, prone position, hemodynamic stabilization, neuromuscular blocking agents), and critical events (hypoxemia, hypoglycemia, hypotension) were associated with HRQOL and RtW.Results: Patients ventilated at ARDS onset with a low tidal volume (VT7ml/kg (45.7±12, p=0.001). In a multivariate adjusted dichotomized analysis, a better mental 3-month SF-12 was observed in the higher VT-group (mean 43.1±12) compared to the lower VT-group (39.5±9, p=0.042), while a dichotomized analysis for driving pressures (14 mbar) did not show any difference neither in PaCO2 levels nor in HRQOL parameters. A decrease in the mental (6-month: 40.0±11 vs 44.8±13, p=0.038) and physical SF-12 (12-month: 38.3±11 vs 43.0±13, p=0.015) was reported from patients with hypoglycemia (blood glucose =65 mmHg was associated with an impaired physical SF-12 (6-month: 38.8±10) compared to less vasopressor use (43.0±11, p=0.019).Conclusions: In acute management of ARDS, a lower VT strategy associated with hypercapnia, as well as the frequent usage of catecholamines and the management of blood glucose may influence short-term HRQOL of survivors. The awareness of these findings is of clinical importance for the acute and post-ICU care.Hintergrund: Die Qualität der aktuellen Behandlungsstrategie (Beatmungseinstellung, rescue-Maßnahmen, unterstützende Intensivtherapie) sowie die Vermeidung kritischer Ereignisse verbessern das Überleben von Patienten mit schwerem akuten Lungenversagen (ARDS). Es ist bisher wenig bekannt darüber, ob eine solche Behandlungsqualität auch einen Einfluss auf die gesundheitsbezogene Lebensqualität (health-related quality of life, HRQOL) und die Rückkehr in das Arbeitsleben (return to work, RtW) der Überlebenden hat. Wir untersuchten eine mögliche Beziehung zwischen akuter Behandlungsqualität, HRQOL und RtW ein Jahr nach Überleben eines ARDS.Methoden: Die prospektiv-multizentrische Studie wurde in 61 Intensivstationen (ICUs) in Deutschland durchgeführt. Drei, sechs und zwölf Monate nach Verlegung von der ICU gaben 396 Überlebende über ihre HRQOL (Short-Form-12) und RtW Auskunft. Die Parameter der akuten Behandlungsqualität (lungenprotektive Beatmungseinstellung, Gradient zwischen endexpiratorischem und inspiratorischem Beatmungsdruck (driving pressure), Einsatz von Bauchlagerung und/oder Muskelrelaxantien, hämodynamische Stabilisierung) und die Häufigkeit kritischer Ereignisse (Hypoxämie, Hypoglykämie, Hypotension) wurden mit HRQOL und RtW assoziiert.Ergebnisse: Patienten, die zu Beginn des ARDS mit einem niedrigen Tidalvolumen (VT7 ml/kg (PaCO2 45.7±12, p=0.001). In einer multivariaten adjustierten dichotomisierten Analyse wurde eine bessere 3-Monats-Lebensqualität in der mentalen Domäne des SF-12 in der Gruppe mit einem höheren VT gefunden (Mittelwert 43.1±12) im Vergleich zu den mit niedrigerem VT beatmeten Patienten (39.5±9, p=0.042); für eine dichotomisierte Analyse des driving pressure (14 mbar) wurde weder für PaCO2 noch für HRQOL ein Unterschied gefunden. Eine Einschränkung der mentalen (6 Monate: 40.0±11 vs 44.8±13, p=0.038) und körperlichen SF-12 Domäne (12 Monate: 38.3±11 vs 43.0±13, p=0.015) wurde für Patienten berichtet, die während der akuten Behandlung eine Hypoglykämie (Blutglukose-Wert =65 mmHg) war mit einer Einschränkung der körperlichen Domäne des SF-12 verknüpft (6 Monate: 38.8±10) im Vergleich zu weniger Vasopressoren-Einsatz (43.0±11, p=0.019).Schlussfolgerung: Im Rahmen des akuten Managements von ARDS-Patienten führten sowohl die empfohlene lungenprotektive Beatmungsstrategie mit niedrigem Tidalvolumen (<7 ml/kg) und Hyperkapnie, als auch der Einsatz von Vasopressoren zur Blutdruckstabilisierung zu einer größeren Einschränkung der Lebensqualität im ersten Jahr nach Überleben. Die Vermeidung kritischer Ereignisse (Hypoglykämie) war mit besserer Lebensqualität verknüpft. Diese Ergebnisse sind für die Nachsorge-Strategie von Patienten nach ARDS von Bedeutung