in the previous issue of critical care , hamzaoui and colleagues present an observational study on the haemodynamic effects of norepinephrine in septic patients with life - threatening hypotension . within 6 hours of admission to the intensive care unit , a threshold mean arterial pressure ( map ) 65 mmhg was selected to commence an infusion of norepinephrine , regardless of the degree of prior volume resuscitation . measurements of cardiac index and derived indices of preload ( end - diastolic global volume index ) and stroke volume variation were made at baseline and following augmentation of map with norepinephrine . the patients were further categorised according to baseline left ventricular ejection fraction and whether they were able to achieve the target map . the investigators found that norepinephrine significantly increased map to a median value of 75 mmhg , which was associated with significant increases in cardiac output and indices of stroke volume and preload . this effect was consistent independent of baseline left ventricular ejection fraction - apart from those patients with left ventricular ejection fraction < 45% , who attained map > 75 mmhg . the authors concluded that the early administration of norepinephrine directed at achieving a target systemic perfusion pressure was achievable through parallel increases in cardiac output and preload . although hamzaoui and colleagues ' study is observational and single - centred in a relatively small population of septic patients using derived indices from pulse contour analysis to quantify changes in preload and contractility , the results are consistent with physiological models that define the protean haemodynamic effects of endogenous catecholamines , specifically norepinephrine , under homeostatic and pathological conditions . norepinephrine exhibits sympathetic activity over an expanding population of adrenoreceptors on the circulation ( 1a and 1b , 2a , 2b and 2c , 1 , 2 and 3 ) , acting centrally on the myocardium , on the arterial ( conduit ) circulation and on the venous ( capacitance ) circulation . haemodynamic function at any point in time represents the balance between the two circulations , so that changes in one are represented by compensatory changes in the other . under pathological conditions such as septic shock , qualitative and quantitative changes in cardiac function and vascular responsiveness result in unpredictable cardiovascular responses between and within individuals , initially as a compensated high output or vasodilated state to a decompensated low output or vasoplegic state . teleologically , this represents exhaustion of endogenous neurohumoral responses induced by pathological processes or an overwhelmed host response . in this context , the use of exogenous infusions of catecholamines , such as norepinephrine or epinephrine , should be seen as neurohormonal augmentation therapy to defend decompensating haemodynamic function rather than as a rescue therapy to treat shock . this understanding is somewhat at variance to traditional clinical practice , supported by current guidelines that recommend haemodynamic resuscitation follows a step - wise approach - initial fluid loading , followed by the use of an inotrope to improve cardiac output , followed by a vasopressor to squeeze the circulation to augment the perfusion pressure . three recently published randomised controlled trials comparing the effects of catecholamines in severe sepsis have demonstrated equivalence in haemodynamic responses without adverse effects on organ function or mortality [ 8 - 10 ] . of the three catecholamines studied , norepinephrine was associated with the lowest incidence of drug - specific side effects compared with epinephrine ( hyperlactataemia and hyperglycaemia ) and dopamine ( arrhythmias ) . on the basis of these studies and a recent commentary furthermore , these trials represent a perceptible change in clinical practice to preferentially use catecholamines early in resuscitation to defend map as the principal haemodynamic endpoint , although it is acknowledged that there is little evidence or agreement on an optimal perfusion pressure in septic shock . the justification for selecting map is based on pragmatic reasons - map is easy and accurate to measure - as well as it being an aggregate index of organ perfusion pressure . however , as there is little direct relationship between perfusion pressure and venous return , which remains difficult to measure under clinical conditions , clinicians rely on the assumption that parallel changes in the arterial and venous circulations will occur . the use of norepinephrine as a neurohormonal augmentation therapy by hamzaoui and colleagues demonstrated inotropic and vasopressor responses in a heterogeneous population of patients with severe sepsis using current monitoring techniques . these data are consistent with established biological and basic science evidence , and provide additional strength to the argument for viewing norepinephrine as a neurohormone rather than as a vasopressor and to recommend its early use as the first - line agent for life - threatening hypotension .
septic shock causes unpredictable cardiovascular responses through adrenoreceptor - mediated changes in cardiac function and vascular responsiveness . 
 the use of norepinephrine should be regarded as neurohormonal augmentation therapy to defend decompensating haemodynamic function rather than as a rescue therapy to treat shock . 
 recent trials represent a perceptible change in clinical practice to preferentially use norepinephrine early in resuscitation to defend the mean arterial pressure and to use norepinephrine as a neurohormone rather than as a vasopressor .