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Mario Ganau: SIRS EANS2011

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Mario Ganau

on 4 May 2011

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Transcript of Mario Ganau: SIRS EANS2011

Systemic Inflammatory Response Syndrome
in SAH and ICH new pathophysiological and therapeutic viewpoints Mario Ganau* MD MSBM, Lara Prisco° MD, Giorgio Berlot° MD
*Graduate School of Nanotechnology - University of Trieste (Italy)
°Department of Perioperative Medicine, Intensive Care and Emergency - University of Trieste (Italy) EANS TRAINING COURSE - TALLINN FEBRUARY 24, 2011
AND KEY POINTS O CEREBRAL INFLAMMATORY RESPONSE AND ITS PREDICTORS O C H O 6 12 6 O O O O C C C C C H H H H H H H H H H H H TRAINEE LECTURE COMPETITION - ESTONIA Systemic Inflammatory Response Syndrome (SIRS) is the clinical expression of the activation of complex intrinsic mediators of the acute phase reaction.

At times, SIRS can compromise the function of various organs and systems resulting in Multiple Organ Dysfunction Syndrome (MODS) TBI SAH SIRS ICH TBI
ICH 29 - 87% 39 - 89% 29 - 53% Tam AK et al.: Neurocrit Care 2010 Godoy D et al.: Rev Neurol 2005 Zygun DA et al.: Crit Care Med 2005 INCIDENCE Power of MDT in predicting:

amplitude of glicemic excursion
presence of hyper and hypoglicemic events
distance between the mean glicemia and the desired threshold (140mg/dl = 7.73mmol/l) Compared with existing glucose variabilty indexes MDT showed the higher sensitivity according to ROC analyses A B C D
A 20 142 26
B 10 141 13
C 41 181 14
D 47 180 43 B better than A

C better than D

B better than C the lower the MDT, the lower SD
the lower the MDT, the closest the MBG value to the desired threshold (140mg/dl) Outline SIRS: definition and incidence

Cerebral inflammation and its predictors

Experimental study on MDT

Final remarks and future perspectives Mean Delta Threshold Prisco L, Ganau M, Zornada F et al. Eur J Anaesthesiol 2011

"A new measure of glucose variability in acute brain injured patients: preliminary results" Experimental evidence has suggested that hyperglycemia may exacerbate CNS injury and negatively affect neurological recovery in TBI, ICH and SAH patients.

Although pre-existing diabetes has not consistently shown to portend a significant worse prognosis in neurosurgery

it remains to be clarified whether admission hyperglycemia, a solitary hyperglycemic event, or persistent hyperglycemia is predictive of poor outcome,
keeping in mind that acute reduction in serum glucose may as well induce brain metabolic crisis and create the basis for a poor clinical course the burden of systemic inflammatory response predicts incidence of vasospasm and poor outcome after sah Dhar R et al. Neurocrit Care 2008 A retrospective analysis was conducted to elucidate the incidence of SIRS in SAH and ICH patients admitted to our ICU after urgent surgical treatment (i.e. aneurysm clipping or coiling, removal of parenchimal hemorrhage). Data were compared to those retrieved from a control group of historic ICU TBI patients (i.e. admitted after removal of brain contusion or positioning of ICP monitoring).

In order to avoid selection biases for the purpose of the hypothesis tested in the present study diabetic patients were excluded from enrollment. McGirt MJ et al. J Neurosurg 2007 Kavanagh BP et al. NEJM 2010 procalcitonin (PCT) levels,
leucocyte and neutrophil counts,
C-reactive protein (CRP) levels,
IL-1, IL-6, TNF, etc Dynamics of classical markers of inflammatory response:

Mixed effect models and multivariable analysis using the generalized estimating equation were employed to assess correlated data (clinical course) with repeated measures of selected biomarkers (SIRS predictors). Differences between groups were calculated with non-parametric tests (Mann Whitney and Wilcoxon) and p < .05 was considered to indicate statistical significance. PATIENTS DATA systemic stress, evaluated by the presence of SIRS and SOFA score, is higher on admission with decreasing trend along the following days in ICH and TBI patients,

SAH PATIENS show a greater tendency to develop a long-lasting SIRS and organ dysfunction later on (after the 3rd day).

Among inflammatory markers, serum procalcitonin (PCT) demonstrated to be the most sensitive but even unspecific one, as depicted by its dynamic: early “bell phenomenon” with an appearing peak in the 2nd day in the three groups.

Among GV indexes the MDT trend over the first 5 days confirmed to be the most reliable and better correlated with the SOFA curve profile, this is particularly significant in SAH patients. The three groups resulted similar in co-morbidities and severity of clinical conditions, as shown by the initial GCS and APACHE II scores; moreover clinical course and radiological findings did not diverge statistically (p > .05).

The stepwise introduction of biomarkers into the multivariate logistic regression model resulted in the selection of MDT as the variable characterized by the overall stronger correlation with clinical course at follow up in SAH and TBI patients MDT dichotomization as: 1 if MDT >25 mg/dl and 0 if <25 mg/dl
OR 2.04, 95 CI 0.79 to 5.23 and OR 2.3, 95 CI 0.91 to 5.66 respectively, p < .05. These findings highlight that a major source of preventable morbidity after cerebral accidents, particularly SAH, is delayed systemic stress, and altered glucose levels

Our data support the hypothesis that MDT could be employed as a major predictor of SIRS and organ dysfunction.

Controlling blood glucose appears strategic in the effort to reduce secondary brain injury and maximize good neurological outcome especially in those cerebral accident, such as SAH and TBI, more prone to set off a systemic dysfunction.
hyperglycemia alters endothelial autoregulation and increases free radical production after SAH

lowers the neuronal ischemic threshold and potentiates inflammatory cell migration after TBI. In the upcoming future therapeutics advances will come from a real-time and high-throughput analysis of relevant biomarkers: our work suggests that MDT may indirectly help the stratification of such critical patients identifying those at higher risk since their first days of stay in ICU.

It is arguable that the ongoing development of nanotechnological arrays for multiparameter invasive continuous monitoring will soon provide an enhanced postsurgical management, reduce the burden of the disease and improve the efficacy of neuroprotective pharmacological therapy. and clinical evidence... Lanzino G et al. J Neurosurg 1993
Kawai N et al. Acta Neurochir 1998
Claassen J et al. Crit Care Med 2004
Juvela S et al. J Neurosurg 2005 Our data cope to experimental evidence... Vlassara H et al. Science 1988
Bucala R et al. J Clin Invest 1991
Wagner KR et al. J Cerb Blood Flow Metabol 1992
Nishikawa T et al. Nature 2000
Baird TA et al. Stroke 2003 suggesting that:
scheme for continuous glucose monitoring in interstitial fluid using glucose oxidase-based sylicon mems (micro electro mechanical system) Piechotta G. et al. Biosens Bioelectron 2005 cases
SAH and ICH controls
R+ posterior communicating artery aneurysm
FISHER: 3 - diam: 5mm
hH: 4 - APACHE II: 23
GOS ICU: 3 - GOS HOSp: 4 69-Y FEMALE - sah
anterior communicating artery aneurysm
FISHER: 3 - diam 4.5 mm
HH: 3 - APACHE II: 21
or: Coiling
GOS ICU: 1 PRE-OP POST-OP OUT OF ICU Pt # 1 Pt # 2 Pt # 1 Pt # 2 MBG: 154 mg/dl (8.5 mmol/l)
MDT: 18 mg/dl MBG: 145 mg/dl (8 mmol/l)
MDT: 33 mg/dl ? ? BNP: 47.8 pg/ml BNP: 580.5 pg/ml
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