in ischemic stroke , the main hemodynamic target for acute therapy focuses on restoring and optimizing the penumbral perfusion 1 . with or without acute recanalization measures 1 map ( mean arterial blood pressure ) is used as a standard target parameter for improving cp ( cerebral perfusion ) being a readily accessible monitoring parameter on one side as well as its expected relation to cp due to vascular autoregulation of the brain and perfusion pressure on the other 2 , 3 . mean arterial blood pressure results from a product of co ( cardiac output ) and total svr ( systemic vascular resistance ) 4 , hence map is expected to correlate with co. in case of insufficient map fluids are administered based on the frank starlingprinciple : the increase in preload leads to a larger co until stroke volumes become constant with optimal preload . in case of insufficient result vasopressors former studies have shown that map levels ' correlations to co hold true only during isovolemic state 4 , 5 . furthermore , it has been shown that co has a linear relationship with organ perfusion 6 . co might therefore be a relevant parameter to increase penumbral perfusion in patients with ischemic stroke . patients admitted to the neurological intensive care unit of university hospital freiburg during 2008 and 2013 who were diagnosed with large ischemic stroke of the mca ( middle cerebral artery ) territory via ct or mri and underwent hemicraniectomy and hypothermia treatment were included in this prospective observational study . the patients included received advanced cardiac monitoring with a vigileo or picco system ( pulsion or flotracksystem , edwards life , irvine , california , united states of america ) according to the in housemonitoring protocol . advanced monitoring was used in addition to standard monitoring of map in patients with the following characteristics : ( 1 ) ischemic stroke > 30% of the middle artery territory ; ( 2 ) hemicraniectomy or hypothermia treatment ; ( 3 ) impaired cardiac function ( e.g. , due to cardiomyopathy , acute myocardial infarction ) ; ( 4 ) conditions effecting cardiac function due to metabolic changes ( e.g. , patients with subarachnoid hemorrhages ) ; and ( 5 ) severe infections . those systems perform an analysis of the arterial pulse contour and calculate a ci ( cardiac index ; index results from co and stroke volume related to body surface ) 4 . we assessed basal mean map , ci , and svrilevels , hemodynamic medication , their effect on hemodynamic parameters and time needed to accomplish aimed normal cardiac index levels of > 3 and < 5 . normal map was stated at > 80 mmhg due to aimed cp pressure of 70 mmhg and assumed normal intracranial pressure of 10 mmhg . fluid replacement or catecholamine administration ( noradrenaline or dobutamine ) was carried out in order to achieve normal levels of map and ci . statistical analysis was performed with student 's ttest or signed ranktest according to distribution level . a spearman 's analysis was carried out to calculate correlation of map and ci parameters at start and end of monitoring , at point of normal map and after optimizing treatment . we included 27 patients ( 19 male , eight female , aged 1977 years ) . mean score of nihss ( national institute of healthstroke scale ) at hospital admission was 17.1 ( 5.8 ) and of mrs ( modified rankin scale ) 4.8 ( 0.6 ) . nihss at discharge was 16.7 ( 7.7 ) and mrs 5.1 ( 0.6 ) , respectively . monitoring was performed via vigileo ( nine patients ) and picco system ( 18 patients ) . initial measure to increase map and ci was fluid replacement : colloids ( 916  801 ml in six patients ) , crystalloids ( 836  474 ml in 11 patients ) , erythrocytes ( in case of hemoglobin < 7 mg / dl ; 750  212 ml in two patients ) , or albumin ( in case of albumin < 2.0 g / dl ; 200 ml in one patient ) . furthermore , catecholamines , noradrenaline ( 0.57 g / min  0.49 g / min in 23 patients ) , or dobutamine ( 15 mg / min  9.3 mg / min in 13 patients ) , were administered . in seven patients , the noradrenaline dose was reduced from 0.44 g / min ( 0.27 ) to 0.23 g / min ( 0.21 ) , in one patient dobutamine was reduced from 10 mg / min to 7.5 mg / min . five patients did not need a change in treatment with ongoing noradrenaline treatment of 0.58 g / min ( 0.35 ) and dobutamine administration with 10 mg / min ( 7.9 ) . the mean time to accomplish normal ci was 6 h ( 6 h ) , map then was 90.4 mmhg ( 12.6 ) . target values for map was accomplished 92.2% ( 10.4 ) and for ci was 82.9% ( 20.1 ) of the time . effects of treatment on map and ci levels mean levels ( standard distribution ) of map ( mean arterial pressure ) and ci ( cardiac index ) levels . spearman 's correlation analysis showed no correlation of map and ci levels ( r = 0.1 ) with a significance level of p < 0.01 throughout the entire study period ( fig . neither did the two parameters correlate in the beginning of monitoring ( r = 0.229 , p = 0.251 ) nor at the end ( r = 0.105 , p = 0.603 ) . no correlation could be detected at normal map levels ( r = 0.199 , p = 0.319 ) or at normal ci levels ( r = 0.229 , p = 0.251 ) . svrivalues of patients with picco monitoring revealed little correlation of svri and map ( r = 0.3 , p < 0.0001 ) , but a significantly negative correlation of svri and ci ( r = 0.8 , p < 0.0001 ; fig . correlation analyses of ci ( cardiac index ) , map ( mean arterial blood pressure ) , and svri ( systemic vascular index ) . our results challenge the current state of the art guiding hemodynamic therapy by maplevels since they show no correlation of map , co and svri . up to date former studies have shown that bp ( blood pressure ) levels influence neurological outcome : leonardibee et al . 7 describe a ushaped relationship with higher risks of death with bp < 150 mmhg or > 150 mmhg in acute ischemic stroke , with a greater negative effect of hypotensive bp . furthermore , bp < 140 mmhg in patients receiving acute endovascular recanalization was a negative predictor for a poor neurological outcome 8 , 9 . in the longterm a low bp might have a negative effect on neurological functions 10 . furthermore , it has long been established that map is a product of co and svr ; correlations of these parameters are expected . greater co results from increased preload until optimal preload levels lead to a constant co. according to the frank starlingprinciple preload and vascular resistance should therefore be optimized 4 , 5 . however , we were able to demonstrate that levels of ci and map do not correlate , regardless of increasing preload via volume administration or svri via noradrenaline therapy . furthermore , we could demonstrate that map and svri correlate little only , whereas ci and svri show a negative relationship . as optimal penumbral perfusion is targeted to reduce the final infarction volume 1 , cp , dependent on cerebral perfusion pressure in regions with impaired autoregulation , needs to be adapted 2 , 11 . our data show that both hemodynamic monitoring and therapy are clinically important in order to increase ci , since it has been shown that they reduce the length of the stay on intensive care units 12 . the effects of hemodynamic treatments are similar to other studies 13 ; in other studies lower dosages of catecholamines were applied 14 , 15 ; targeted map levels were accomplished to 92% of monitoring time . as we and others could show that maplevels do not necessarily correlate with ci and secondary cp due to its dependence on volume state ci levels some studies did not detect a correlation of ci and cp 11 , whereas others show that elevated ci increases cp : partial aortic occlusion in pigs 16 and passive leg raising lead to a significant higher cp due to shifting of blood volume 5 . extending ci apart from maplevels via volume extension by albumin or hydroxyethyl starch solution in healthy men or sepsispatients improves cp 17 . in monkeys with mcaocclusion , cerebral blood flow increased by volumeguided augmentation of ci , independently of mapchanges 18 . in a case report by duke 15 hyperdynamic therapy with increasing co > 8 by dobutamine ( 520 g / kg / min ) and albumin infusion lead to a normal neurological exam after 6 months in a formerly hemiplegic and severe aphasic patient . similar results were found in patients with sah ( subarachnoid hemorrhage ) when hyperdynamic therapy ( albumin and dobutamine treatment 510 g / kg / h ) could reverse ischemic symptoms 14 . in accordance with these results sahpatients with poor cardiac function were more likely than patients with good cardiac function to experience infarction due to vasospasms 19 . furthermore , it could be shown that optimizing hemodynamic parameters ( preload , ci ) effects a better outcome 20 , 21 . changes in hemodynamics following catecholamine use in our patients may vary : using vasopressors in patients with insufficient preload and in patients with preexisting left ventricular insufficiency enhancement of map may lead to reduced ci 5 . patients with atrial fibrillation or beta blockertreatment show a limited potential to increase ci and secondary cp 6 . as stroke patients often suffer from cardiac diseases the indirect effect on cp needs to be assessed in further investigations . as others show a cidependent change in cp we expect to apply this for the penumbral region in patients with large stroke .
key clinical messagethis case series of 27 patients with large stroke challenges the current state of the art guiding hemodynamic management by blood pressure levels . 
 the results show that assumed correlations of blood pressure , cardiac output , and systemic vascular resistance do not exist . 
 therefore , hemodynamic therapy may better be guided by cardiac output .