{"id":5296,"date":"2011-07-14T20:25:14","date_gmt":"2011-07-14T20:25:14","guid":{"rendered":"http:\/\/crashtext.org\/misc\/5296.htm\/"},"modified":"2015-06-08T11:05:03","modified_gmt":"2015-06-08T15:05:03","slug":"shock-vasoactives","status":"publish","type":"post","link":"https:\/\/crashingpatient.com\/resuscitation\/shock-vasoactives.htm\/","title":{"rendered":"Shock and Vasoactive Agents"},"content":{"rendered":"
vasoactive handout<\/a><\/p>\n another good review of the drugs<\/a><\/p>\n Chad’s Vasoactive Handout<\/a><\/p>\n <\/p>\n Best Circulatory Review<\/a> (Chest 2002;121:877)<\/p>\n Best review of Guyton Graph<\/a> and adding kidney to the mix<\/p>\n <\/p>\n Integrative Physiology<\/a><\/p>\n Titrate the Vasopressors<\/a><\/p>\n Inotrope Review<\/a><\/p>\n Interpretation of Blood Pressure<\/a><\/p>\n There is no descending limb on a starling curve<\/a><\/p>\n <\/a><\/p>\n Best article on VR and CVP physiology (Anesthes 2008;108(4):735)<\/p>\n Shock Dx:<\/strong> Feel the Feet Look at the Neck Veins Echo ABD Uts\/Fast C-XR Fingerstick 12 Lead Rx:<\/strong>NorEpi Epi Phenylephrine Bolus Ephedrine Bolus CaCl Fluid Dobutamine Decadron Monitoring:<\/p>\n Preload=LVEDV<\/p>\n there is no descending limb of starling, fluid can’t affect hemodynamics<\/p>\n but you can cause tissue and lung edema which can effect tissue ox<\/p>\n preload doesn’t = fluid responsiveness<\/p>\n <\/p>\n venoconstriction can release 60-80% of the blood volume, increasing preload \u00a0 Afterload-impedance to ventricular ejection \u00a0 Lusitropism-the ability to relax during diastole \u00a0 afterload dominates in the failing heart to determine CO \u00a0 Norepinephine leaches fluids out of the vesselsIncreasing MAP with norepi beyond 65 does not increase microcirc flow (Crit Care 2009;13:R92)<\/p>\n <\/p>\n <\/p>\n <\/a><\/a><\/p>\n <\/p>\n <\/p>\n Bathmotropic is one of five adjectives used to describe various qualities of the cardiac cycle; the other four are: inotropic<\/a> chronotropic<\/a> dromotropic<\/a> and lusiotropic<\/a>. In an article in the American Journal of Medical Sciences these five terms were described as the five fundamental properties of the heart.[3]<\/a> While Bathmotropic, as used herein has been defined as pertaining to modification of the excitability of the heart it can equally well refer to modification of the irritability of heart muscle, and the two terms are frequently used interchangeably.[4]<\/a><\/p>\n <\/p>\n <\/p>\n Norepi improves CI, SVI, and LVSWI in patients unresponsive to dobutamine, but doesn’t cause improvement in patients not on dobutamine b\/c they already have a high cardiac index (Martin Crit Care Med 1999;27(9):1708)<\/p>\n <\/a><\/p>\n Best Review (Inten Care Med 2009;35:45)<\/a><\/p>\n <\/a><\/p>\n Fig.\u00a02\u00a0Interactions of venous return and cardiac function. a<\/strong> Magder\u0092s representation of the circulatory system. Modified from [8<\/cite>], with permission. MSFP mean systemic filling pressure. Detailed explanations in the text (beginning of Sect.\u00a0\u0093Venous return curve\u0094). b<\/strong> Venous return curves (later part of Sect.\u00a0\u0093Venous return curve\u0094). c<\/strong> cardiac function curves (Sect.\u00a0\u0093Cardiac function curve\u0094). d<\/strong> Guyton\u0092s graphical analysis of cardiac output regulation (Sect.\u00a0\u0093Graphical analysis of cardiac output\/venous return\u0094). e<\/strong> Potential effects of generalized venoconstriction on cardiac output (last paragraph of Sect.\u00a0\u0093Graphical analysis of cardiac output\/venous return\u0094). In panels b\u0096e<\/strong>, RAP designates right atrial pressure relative to atmosphere<\/em><\/p>\n <\/p>\n <\/p>\n Circulatory Model \u00a0 \u00a0 The care of the critically ill hemodynamically unstable patientoften proceeds along the following two parallel paths: physiologic resuscitation and differential diagnosis investigation. Frequently, the initial physiologic characterization and the subsequent physiologic response to therapy contribute to establishing the definitive diagnosis and initiating optimal treatment. Accordingly, the utilization of a universally applicable physiologic modelof the circulation that allows for the expeditious applicationof resuscitative and diagnostic strategies is beneficial. Thisis particularly pertinent to MPE, given the acknowledged difficultyin deciphering the process, the potential for rapid lethality,and controversies in treatment. A fundamental understandingand review of basic hemodynamic principles is imperative toappreciate the pathophysiologic alterations induced by variousdisease states. Utilizing Poiseuille\u0092s law, conventionalhemodynamics conceptualize the circulatory system as an opencylindrical conduit with cardiac output (CO) defined as a functionof pressure gradients (mean arterial pressure [MAP] – rightatrial pressure [RAP]) against resistance (Fig 2<\/a>). However,recognizing that CO is pulsatile, it is useful to devise a modelthat includes a hydraulic pump.<\/p>\n Poiseuille\u0092s law representing the relationships among flow (Qflow), pressure, and resistance.<\/p>\n <\/a>Figure 3<\/a> illustrates a three-compartment circulatory modelthat conceptualizes the circulatory system as a hydraulic pump composed of a right heart pump linked in series to a left heartpump. As a consequence of this serial hydraulic alignment, COcannot exceed venous return (VR) and vice versa. In other words,left heart output cannot exceed right heart output, which allowsfor the conceptualization of both pumps as a single hydraulicunit. The hydraulic pump is primed with volume from the venouscapacitance bed [ie<\/em>, the volume reservoir] and empties intothe arterial impedance bed (ie<\/em>, the resistive element). Guytonet al49<\/a> recognized that the pressure gradient for VR is theratio of pressure in the venous capacitance bed (PVC) to theRAP (VR = PVC – RAP), thus establishing the integral role ofthe right atrium (RA) as a coupler of the venous system andcardiac hydraulic circulation. The graphic solution of thisobservation is depicted in Figure 3<\/a> . PVC is a function of venousvolume and vascular tone, which must exceed the RAP to maintainVR. The RAP provides not only an assessment of the pressurein the right heart but an indirect gauge of the pressure inthe venous capacitance system. Thus, the circulatory systemcan be defined as a three-compartment model; a capacitance bedthat provides volume to a hydraulic pump that generates flowinto an impedance bed. Any hemodynamic abnormality can be characterizedby disturbances of one or more of these three variables. Thesurrogates for venous capacitance pressure, hydraulic pump function,and impedance are RAP, CO, and systemic vascular resistance(SVR), respectively. Invasive monitoring is frequently not inplace on initial presentation, and, given the controversiessurrounding its risks and benefits,50<\/a> it is prudent to utilizereadily available physical examination surrogates to definethe model variables. Estimation of the RAP from the internaljugular vein approximates the pressure in the venous capacitancesystem, and the pulse character and temperature of the extremitiesapproximate impedance (resistance). Warm flushed extremitieswith a wide pulse pressure indicate low impedance (ie<\/em>, resistance),whereas cool constricted extremities with a narrow thready pulsesuggest high impedance (ie<\/em>, resistance). The latter is a consequenceof the catecholamine-mediated vasoconstriction that is initiatedto create perfusion pressure gradients to redistribute and optimizethe low-flow state. In shock patients, flow and resistance arealmost uniformly reciprocal (Qflow x resistance = pressure orCO x SVR = BP). Therefore, the initial assessment of impedance(ie<\/em>, resistance) allows for the inferential derivation of hydraulicflow (ie<\/em>, CO). Obviously, invasive monitoring will be neededif the physical examination findings cannot be well-characterized.Representative examples are illustrated in Figure 3<\/a> .<\/p>\n <\/p>\n <\/a><\/a><\/p>\n <\/p>\n <\/p>\n Pathophysiology<\/p>\n Mechanism of Cardiac Failure<\/strong> Cardiac failure from MPE results from a combination of the increased wall stress and cardiac ischemia that comprise RV function andimpair left ventricular (LV) output. Research from animal modelsand evidence from clinical investigations clearly demonstratethat the impact of embolic material on the pulmonary vascularoutflow tract precipitates an increase in RV impedance. Thisinitiates the vicious pathophysiologic cycle depicted in Figure 4<\/a>. The degree of increase in RV impedance is predominantlyrelated to the interaction of the mechanical obstruction withthe underlying cardiopulmonary status.51<\/a>52<\/a>53<\/a> Additional factorsreported to contribute to increased RV impedance include pulmonary vasoconstriction induced by neural reflexes,54<\/a> the releaseof humoral factors55<\/a> from platelets (ie<\/em>, serotonin and plateletactivating factor), plasma (ie<\/em>, thrombin and vasoactive peptidesC3a, C5a), tissue (ie<\/em>, histamine), and systemic arterial hypoxia.56<\/a> The acute development of this increased RV impedance constitutesa pressure afterload on the RV and has multiple effects on RVand LV function.<\/p>\n Given the reciprocal relationship between RV stroke volume and vascular load, RV stroke volume will diminish with increasingload.57<\/a> Initially, the compensatory maintenance of CO is achievedby a combination of catecholamine-driven tachycardia and theutilization of the Frank-Starling preload reserve (the latterbeing responsible for RV dilatation). This increase in RV cavitarypressure and radius serves to significantly increase RV wallstress (wall stress = pressure x radius). This is the primarydeterminant of RV oxygen uptake, thus creating the potential for RV ischemia. With increasing RV load and wall stress, RVsystolic function becomes depressed and CO begins to decrease.Interestingly, systemic BP may be adequately maintained by systemicvasoconstriction at this point.58<\/a> From the point of initialCO depression, it has been reported59<\/a> that increases in loadsufficient to further decrease CO by 20% will result in a disproportionateincrease in end-systolic volume compared to end-diastolic volume.Afterload mismatch has been used to describe the phenomenonof RV pressure work exceeding RV volume work in this setting.60<\/a> As a consequence of this mismatch, LV preload will decrease,given the ventricular alignment in series. LV preload is additionallyimpaired by decreased LV distensibility as a consequence ofa leftward shift of the interventricular septum and of pericardialrestraint, both of which are related to the degree of RV dilatation.61<\/a>62<\/a>63<\/a> It also has been suggested that MPE may impair LV function independentlyof preload mechanisms.64<\/a> In the presence of declining LV forwardflow, MAP can be maintained only by catecholamine-induced vasoconstriction.A further decrease in LV flow results in systemic hypotension.RV coronary perfusion pressure (CPP) depends on the gradientbetween the MAP and the RV subendocardial pressure. Decreasesin MAP associated with increases in RV end-diastolic pressure(RVEDP) impair the subendocardial perfusion and oxygen supply.Elevated right-sided pressures can further impair coronary perfusionand LV distensibility by increasing coronary venous pressure.65<\/a> Increased oxygen demands associated with elevated wall stresscoupled with decreased oxygen supply have been shown to precipitateRV ischemia, which is thought to be the cause of RV failure.66<\/a> Clinical evidence of RV infarction as a consequence of the precedingcondition has been demonstrated in patients with and withoutobstructive coronary disease.67<\/a>68<\/a>69<\/a> A reversal of PE-inducedRV ischemia and RV failure can be accomplished by the infusionof vasoconstrictors to raise aortic pressure and to increasethe coronary perfusion gradient.66<\/a>70<\/a><\/p>\n Translation of the pathophysiology of MPE into the previously discussed three-compartment hydraulic model of the circulationis shown in Figure 5<\/a> . Catecholamine-induced venoconstrictionincreases the PVC to maintain a pressure gradient for VR in response to the PE-induced RAP elevation. The impairment ofRV hydraulic pump function compromises LV hydraulic output,which is manifested as systemic arterial hypotension. Thus,the model variables would reveal an increased RAP, a decreasedCO, and an increased SVR. The clinical correlates would be jugularvenous distention, a thready pulse, and cool extremities, respectively.<\/p>\n <\/p>\n <\/p>\n <\/p>\n 1st Question: Is this patient in shock; is the shock adequately resuscitated<\/p>\n 2nd Question: Does the patient need fluid<\/p>\n <\/p>\n Markers of regional perfusion are really the answer to the first question<\/p>\n CV system consists of a pump (cardiogenic), tubing (distributive), and fluid (hypovolemic)<\/p>\n Shock is malfunction of at least one of the above. It is hypotension with signs of end organ failure<\/p>\n Another way to think about it is a failure of one of the following: stroke volume, heart, or peripheral vascular resistance and a failure of compensation of the other two.<\/p>\n <\/a><\/p>\n <\/p>\n Dysoxia-when the production of ATP is limited by oxygen supply<\/p>\n <\/p>\n Inadequate Venous Return<\/p>\n Signs= a lingering tachycardia, cold peripheries or a pulse oximeter that is not reading, oliguria, low CVP, a large base excess on blood gas analysis, a lactic acidosis. In this state, patient can become hypotensive from medications such as sedatives.<\/p>\n Diastolic Dysfunction = stiff heart, requiring higher filling pressure to achieve normal volume. 2) Diastolic Dysfunction: loss of left ventricular compliance impairs it\u0092s ability to receive blood. This disorder most commonly results from systolic dysfunction, and as a consequence of myocardial fibrosis \u0096 for example due to ischemia or hypertension. Diastolic dysfunction is characterized by the requirement of higher filling pressures to achieve normal filling volumes, while the heart is less compliant and receptive to blood. Aggressive volume loading of patients with diastolic dysfunction frequently results in backward heart failure, causing acute pulmonary edema. Cardiac inflow obstruction is caused by a pericardial (tamponade) or intrathoracic process (PEEP), or a lesion within the heart itself (mitral stenosis). 3) Cardiac inflow obstruction: occurs either due to a constriction around the heart, a pericardial or intrathoracic process, or a lesion within the heart itself. Pericardial injuries include pericardial effusion or hematoma constrictive pericarditis \u0096 an acute crisis associated with a pericardial injury is called tamponade. Tamponade is diagnosed as a tetrad of shock, clear lung fields, inaudible or muffled heart sounds, and an increase in the jugular venous pulse waveform on inspiration. An often forgotten but extremely common cause of hypotension is excessive intrathoracic pressure. This can be transmitted from within the alveolar space \u0096 as with positive end expiratory pressure (PEEP) and gas trapping in airway obstruction (auto-PEEP), or within the pleural space \u0096 Pneumothorax, hemothorax or, if the patient is in extremis, tension Pneumothorax. Intracardiac lesions may also cause inflow obstruction; these include mitral and tricuspid stenosis or thrombosis, and atrial myxoma.<\/p>\n Systolic dysfunction is pump failure from ischemia or overload<\/p>\n <\/p>\n Cardiac outflow obstruction is caused by pulmonary embolism, aortic stenosis, aortic crossclamps 2. Outflow obstruction: there are two major sites that cardiac outflow may be blocked: at the level of the aortic valve (aortic stenosis) or within the low pressure (at thus easily occluded) pulmonary circulation \u0096 pulmonary embolism. The former can be diagnosed on the basis of history, ECG and classic murmur. The latter may be more difficult to diagnose. Useful information includes risk (cancer, immobility, deep venous thrombosis, lack of prophylaxis, pelvic and hip surgery), ECG changes (right sided \u0096 RVH, sinus tachycardia, atrial fibrillation, right bundle branch block), occasional chest x-ray findings, and definitive diagnosis on ventilation-perfusion scanning, spiral CT or pulmonary angiography.<\/p>\n Peripheral Resistance is caused by sepsis, anaphylaxis, or spinal shock<\/p>\n <\/p>\n In sepsis, there are three fundamental physiologic upsets: increased synthesis of nitric oxide, activation of ATP-sensitive potassium channels in vascular smooth muscle, and deficiency of vasopressin. The plasma concentration of nitric oxide is markedly increased in septic shock. The production of this endogenous vasodilator appears to occur due to the expression of inducible nitric oxide synthetase by cytokines. This agent appears to be responsible for the end organ resistance to catecholamines and endothelin in sepsis.<\/p>\n If patient is awake, talking, and urinating, then hypotension is probably not shock<\/p>\n Look at lactate and base deficit<\/p>\n <\/p>\n Shoot for MAP of 80 in normal folks, 90 in hypotensives<\/p>\n <\/p>\n First look at the heart rate<\/p>\n Second look at volume status<\/p>\n <\/p>\n Complete heart block, atrial fibrillation, tricuspid stenosis and regurgitation will lead to an inaccurate reading: although the diagnosis of these disorders can be made from the CVP waveform<\/p>\n <\/p>\n The central venous pressure should be regarded as a trend. It is conventional to volume load an under-resuscitated patient to a target CVP: I use 8 \u0096 10 mmHg if the non-ventilated patient, and 12 \u0096 16 mmHg, if the patient is on positive pressure ventilation. If there is a question of cardiac disease, cardiac hypertrophy or dilatation or if the patient is middle aged or older, I aim higher \u0096 16 mmHg plus. In many young patients, it is often not possible to raise the CVP above 10 mmHg, such is the efficiency of the cardiovascular system.<\/p>\n <\/p>\n Right atrial pressures are more representative of systemic vascular volume. Indeed with pulmonary hypertension, the use of left sided pressures may seriously overestimate the systemic blood volume. The purpose of PACs is to construct Starling (pressure-volume) curves of the left ventricle, to determine the end diastolic volume pressure relationship that optimizes stroke volume. The left ventricular end diastolic pressure is not measured directly, but through a surrogate \u0096 the pulmonary capillary wedge pressure (PCWP).<\/p>\n <\/p>\n Type<\/strong><\/p>\n HR<\/strong><\/p>\n SV<\/strong><\/p>\n CVP<\/strong><\/p>\n PCWP<\/strong><\/p>\n CO\/CI<\/strong><\/p>\n PR<\/strong><\/p>\n Hypovolemic<\/strong><\/p>\n \u2191<\/p>\n \u2193<\/p>\n \u2193<\/p>\n \u2193<\/p>\n \u2193<\/p>\n \u2191<\/p>\n Distributive<\/strong><\/p>\n <\/p>\n <\/p>\n <\/p>\n <\/p>\n <\/p>\n <\/p>\n Spinal Shock<\/p>\n \u2191<\/p>\n n<\/p>\n \u2193<\/p>\n \u2193<\/p>\n \u2191<\/p>\n \u2193<\/p>\n Anaphylaxis<\/p>\n \u2191<\/p>\n n<\/p>\n \u2193<\/p>\n \u2193<\/p>\n \u2191<\/p>\n \u2193<\/p>\n Sepsis<\/p>\n \u2191<\/p>\n \u2193<\/p>\n \u2193<\/p>\n \u2193<\/p>\n \u2191<\/p>\n \u2193<\/p>\n Cardiogenic<\/strong><\/p>\n <\/p>\n <\/p>\n <\/p>\n <\/p>\n <\/p>\n <\/p>\n Heart Block<\/p>\n \u2193<\/p>\n \u2191<\/p>\n \u2191<\/p>\n \u2191<\/p>\n \u2193<\/p>\n <\/p>\n Pump Failure<\/p>\n \u2191<\/p>\n \u2193<\/p>\n Relatively low<\/p>\n Relatively low<\/p>\n \u2193<\/p>\n \u2191<\/p>\n Vol Overload<\/p>\n \u2191<\/p>\n \u2193<\/p>\n \u2191<\/p>\n \u2191<\/p>\n \u2193<\/p>\n \u2191<\/p>\n Inflow obstruction<\/p>\n \u2191<\/p>\n \u2193<\/p>\n \u2191<\/p>\n <\/p>\n \u2193<\/p>\n \u2191<\/p>\n Outflow obstruction<\/p>\n \u2191<\/p>\n \u2193<\/p>\n \u2191<\/p>\n \u2191<\/p>\n \u2193<\/p>\n \u2191<\/p>\n <\/p>\n Determinants of cardiac output:<\/strong>The cardiac output is the product of the stroke volume and the pulse rate. It is calculated as:<\/p>\n CO = SV * PR.<\/strong><\/p>\n The stroke volume of the left ventricle is ultimately determined by the interaction between its preload, the contractile state of the myocardium and the afterload that the ventricle faces. Unfortunately, there is no simple measure of the ‘contractile state’ and as a result, there is no single equation which describes the relationship between these three parameters.<\/p>\n Preload.<\/strong> That the ‘preload’ or stretch on myocardial fibres at the end of diastole had a significant effect on the subsequent force of contraction was recognised by the physiologist Otto Frank at the end of the nineteenth century 1<\/a> (Figure 1)<\/em><\/strong><\/a>.<\/p>\n This fundamental relationship has since been analysed in great detail and the adjustment of preload by blood volume transfusion or depletion remains one of the most important therapeutic manoeuvres in acute cardiovascular medicine.<\/p>\n In practice, such volume adjustments can be made by various means:<\/p>\n 1. Circulating blood volume can be increased by the administration of fluid, or reduced by the use of diuretics and \/ or fluid restriction.<\/p>\n 2. Venous return can be varied by the adoption of a head-down or head-up posture.<\/p>\n 3. Venous capacitance can be altered by the use of vasoconstrictor or vasodilator therapy.<\/p>\n Contractile State.<\/strong> In its strictest sense, the term ‘contractility’ refers to the inotropic state of the myocardium – that is, the force and velocity with which the myocardial fibres contract. This can be easily measured in an isolated muscle preparation under specified loading conditions, but is notoriously difficult to measure in the intact human.<\/p>\n In clinical practice, various contraction-phase indices such as velocity of fibre shortening, peak rate of ventricular pressure rise and end-systolic pressure:volume relationship (Figure 2)<\/em><\/strong><\/a> are used, but they are all affected by loading conditions to a greater or lesser degree.<\/p>\n The ‘chronotropic’ or ‘rate’ state of the intact heart should also be incorporated into any clinical definition of ‘contractility’ – because variations in the pulse rate can have obvious, important effects on the cardiac output and manipulation of pulse rate by the use of positive or negative chronotropes can be an important therapeutic manoeuvre in sick patients.<\/p>\n It is not possible to make any precise measurements of contractility with a PAC, although it is possible to make reasonable inferences about the contractile state by the use of ventricular function curves (Figure 1)<\/em><\/strong><\/a>. This concept has been developed by Barash et al who have described the use of a ‘Hemodynamic Tracking System’ which defines the relationship between LVSWI and PAOP in patients with normal, slightly depressed and severely depressed ventricular function 2<\/a>.<\/p>\n Adjustment of both the inotropic and chronotropic state of the heart by the use of inotropic drugs is commonly practised in cardiovascular medicine.<\/p>\n Afterload.<\/strong> In physiological terms, afterload can be defined as ‘The sum of all those forces which oppose ventricular muscle shortening during systole’ – although in a clinical sense it is probably more useful to consider systemic vascular resistance as the appropriate measure.<\/p>\n In isolated cardiac muscle, there is an inverse relationship between afterload and the initial velocity of shortening of the muscle (Figure 3)<\/em><\/strong><\/a>. This would suggest a potential dependance of cardiac output on afterload. In fact, in the intact human, the output of the normal heart is relatively unaffected by changes in vascular resistance until afterload becomes quite extreme (Figure 4)<\/em><\/strong><\/a>. This is probably because an increase in afterload leads to an almost immediate, secondary increase in preload by a ‘damming up’ of the blood within the left ventricle. This, in turn, increases end-diastolic volume which enhances contractility through the Frank-Starling mechanism. In contrast, if myocardial function is severely depressed, cardiac output may become crucially afterload-dependent as illustrated in Figure 4<\/em><\/strong><\/a>.<\/p>\n Thus, ‘sick’ hearts can be considered to be relatively preload independent but afterload dependent while the reverse is true for ‘healthy’ hearts. As a result, ‘afterload reduction’ (reduction of systemic vascular resistance by the use of appropriate vasoactive drugs) is of the greatest benefit in those in whom myocardial function is most depressed.<\/p>\n The role of blood viscosity and, indirectly, haemoglobin concentration in determining SVR is often overlooked. Although haemodilution is not commonly used as a therapeutic manoeuvre for afterload reduction, inadvertent haemodilution is often a concomitant of serious illness. Haematocrit and fibrinogen are the most important determinants of blood viscosity and, in turn, contribute significantly to vascular resistance. These relationships are illustrated graphically in Figure 5<\/em><\/strong><\/a>. Because blood is a non-Newtonian fluid, there is no simple expression to relate SVR to haematocrit and fibrinogen levels, however, it is easy to demonstrate the completely passive increase in venous return 3<\/a> and cardiac output which occur during haemodilution 4<\/a>.<\/p>\n Eckmann et al have recently described the effect of variations in haematocrit and temperature on blood viscosity and have derived an equation which predicts blood viscosity as a function of temperature, shear rate, and haematocrit under a wide range of conditions 5<\/a>.<\/p>\n Finally, it should not be forgotten that there is a degree of ventricular interdependence which can determine ventricular performance 6<\/a>. – The position of the interventricular septum (IVS) can alter the compliance of each ventricle under altered loading conditions with secondary effects on contractility. This effect is not usually important, but can become so in conditions such as tension pneumothorax, tamponade, right ventricular infarction etc.<\/p>\n References:<\/strong><\/p>\n 1. Frank O: Zur Dynamik des herzmuskels. Ztschr fur Biol 32:370, 1895<\/p>\n 2. Barash PG, Chen Y, Kitahata LM et al The Hemodynamic Tracking System. Anesth. Analg. 59:169 (1980)<\/p>\n 3. Guyton AC, Richardson TQ Effect of hematocrit on venous return. Circ Res 9:157-163, 1961<\/p>\n 4. LeVeen HH, Ip M, Ahmed N et al Lowering blood viscosity to overcome vascular resistance. Surg Gynecol Obstet 150:139-149, 1980<\/p>\n 5. Eckmann DM, Bowers S, Stecker M, Cheung AT Hematocrit, volume expander, temperature, and shear rate effects on blood viscosity. Anesth Analg 2000 Sep;91(3):539-45<\/p>\n 6. Taylor RR, Covell JW, Sonnenblick EH et al: Dependence of ventricular distensibility effect on filling of the opposite ventricle. Am J Physiol 218:711, 1967<\/p>\n Last edited on:<\/strong> 14\/11\/2000<\/p>\n Go to source: Determinants of cardiac output:<\/p>\n <\/p>\n Pressure volume loops obtained in 3 contractile states.<\/p>\n A ventricle with increased contractility (green) operates at a lower end-diastolic volume and pressure and achieves end-systolic pressure at a lower end-systolic volume. In contrast, a ventricle with impaired contractility (red) operates at a high end-diastolic volume and pressure and achieves end-systolic pressure at a higher end-systolic volume.<\/p>\n The slope of a line drawn from the origin through the end-systolic pressure point is a measure of the contractile state.<\/p>\n Pressure:volume loops with end-systolic points on the same line are generated when loading conditions are changed, but contractility is unaltered.<\/p>\n This measure of contractility is thought to be relatively load-independent, but is very difficult to measure clinically.<\/p>\n Echocardiographic techniques for measuring similar indicators are emerging, but, as with many echocardiographic techniques, require considerable skill on the part of the observer.<\/p>\n <\/p>\n Ventricular function curves describe the fundamental Frank-Starling relationship. – As the amount of ‘stretch’ (preload) on the ventricular fibres is increased in diastole, so the resulting force of contraction of the next beat is increased. Note that in the failing heart (shown in red), the curve is relatively ‘flat’. Under these circumstances, increasing preload will not enhance ventricular performance. In fact, the reverse may occur because wall tension will increase with a concomitant increase in oxygen requirements of the heart.<\/p>\n The green curve represents a heart in which contractility is increased.<\/p>\n In this example, the cardiac output is used as an index of the force of contraction and the PAOP as a measure of sarcomere length.<\/p>\n Repeated measurements of PAOP and output can be made after therapeutic interventions such as volume loading or the use of inotropes. The results can be plotted onto a diagram of the form shown here and a notion of the ‘contractile state’ of the individual patient developed.<\/p>\n <\/p>\n <\/p>\n <\/p>\n <\/p>\n <\/p>\n Endpoints of resuscitation<\/p>\n CVP=15<\/p>\n PAWP=20-22<\/p>\n CI>3<\/p>\n VO2>100cc\/min\/m2<\/p>\n Lactate<4<\/p>\n Base Deficit=-3 to 3<\/p>\n <\/p>\n <\/a><\/p>\n Insult causes decreased O2 delivery to cells (DO2).\u00a0 DO2 is the product of CO and PaO2.\u00a0 The body compensates by releasing epi and norepi which raise the CO.\u00a0 In addition, dopamine, cortisol, glucagon, growth hormone, and anti-diuretic hormone (ADH) are also released.\u00a0 Cells will increase the amount of Oxygen withdrawn from the blood causing decreases from the normal venous sat of 70-75%.\u00a0 When despite this increased extraction there is not enough oxygen, the cells begin anaerobic metabolism and release lactate.\u00a0 Eventually the acidosis surrounding the cells causes membrane disruption and cell death.\u00a0 Eventually, hypoxic cells of the vascular endothelium activate tissue macrophages and leukocytes, leading to the production of numerous harmful inflammatory mediators.7 Mediators that have been implicated in shock include tumor necrosis factor, interleukins 1 and 2, eicosanoids, interferon gamma, and platelet activating factor. With resuscitation, the hypoxic vascular beds are reperfused, resulting in the delivery of these mediators to the systemic circulation. It is this washout of inflammatory mediators that leads to the development of the systemic inflammatory response syndrome (SIRS). Due to compensatory mechanisms, the effects of age, or the use of certain medications, a large percentage of patients in shock will present with a normal blood pressure and heart rate. Thus, normal vital signs cannot be used to exclude the presence of shock. In fact, waiting for hypotension and tachycardia to develop to make the diagnosis invariably will increase patient mortality(EM Reports)<\/p>\n <\/p>\n <\/p>\n Base Deficit-amount of base that must be added to 1 liter of blood to normalize pH<\/p>\n MUST have peep on during all ventilations including BVM<\/p>\n <\/p>\n In fact, strenuous accessory muscle use can increase consumption anywhere from 50% to 100%, leading to a decrease in cerebral blood flow by as much as 50%.3 Thus, the tachypneic patient in shock ultimately may require mechanical ventilation as respiratory muscles fatigue, hypercapnia increases, and acidosis worsens. Advantages to mechanical ventilation include improved oxygen delivery to the alveoli, correction of hypercapnia, and, most importantly, a decrease in oxygen consumption by the respiratory muscles.<\/p>\n CVP<\/p>\n \u0095 Low: < 6 cmH2O;<\/p>\n \u0095 Normal: 6-12 cmH2O;<\/p>\n \u0095 High: > 12 cmH2O<\/p>\n In addition to noting simple engorgement, determine whether the veins remain distended or enlarge with inspiration. Normally, neck veins should collapse during inspiration, because of decreased intrathoracic pressure. In the presence of impaired venous return or elevated right heart pressures, neck veins will paradoxically swell (Kussmaul\u0092s sign). This phenomenon occurs with tension pneumothorax, right ventricular infarction, pericardial tamponade, and massive pulmonary embolism.<\/p>\n <\/p>\n Monitor by BP (Need mean of 60-65), Mental Status, Urine Output, and Base Deficit\/Lactate<\/p>\n <\/p>\n Dobutamine 5-20 ug\/kg\/min<\/p>\n Dopamine 5-20 ug\/kg\/min<\/p>\n Epinephrine 5-20 ug\/min<\/p>\n Norepinephrine: 5-30 ug\/min (0.2-1.3 mcg\/kg\/min)<\/p>\n <\/p>\n Canadian Journal of Anesthesia 55:163-167 (2008)<\/p>\n Stability of norepinephrine infusions prepared in dextrose and normal saline solutions\u00a0Conclusion: Norepinephrine solutions, in concentrations commonly used in the clinical setting, are chemically stable for seven days, at room temperature and under ambient light, when diluted either in D5W or NS.<\/p>\n <\/p>\n <\/p>\n <\/p>\n Phenylephrine 2-200 ug\/min<\/p>\n Auscultatory blood pressure measurement underestimates true arterial pressure in shock by an average of 15 mmHg, particularly when peripheral vascular resistance is high.21,22 However, Doppler measurements of blood pressure in hypotensive patients correlate well with direct arterial systolic blood pressure measurements<\/p>\n <\/p>\n <\/a><\/p>\n In non-crashing patients the MAP from arm cuff correlates with invasive monitoring; ankle and thigh is pretty good as well. Did not include circ collapse patients (Crit Care Med 2012;40(4):1207)<\/p>\n We are not good at detecting hypovolemia by physical exam. Postural tachycardia and dizziness are fairly good, rest are crap (Ann Emerg Med 2005;45(3):327)<\/p>\n dobutamine is a racemic mixture. In a normal person with a low adrenergic state, the partial agonist and antagonist effects of the two enantiomers more or less balance out. In a high-adrenergic state, it is highly likely that *both* enantiomers will antagonise the effects of alpha agonists at the alpha receptor. My understanding is that the *affinity* of dobutamine for the alpha receptor is about 20 times that of noradrenaline (norepinephrine).<\/p>\n <\/p>\n Receptor Stimulation by various Catecholamines AGENT <\/strong> Alpha 1 <\/strong> Alpha 2 <\/strong> Beta 1 <\/strong> Beta 2 <\/strong> Beta 3 <\/strong> Dopaminergic <\/strong> Adrenaline (epinephrine) \u00a0+++ \u00a0+++ \u00a0++ \u00a0++ \u00a0++ – Noradrenaline (norepinephrine) \u00a0 \u00a0++ \u00a0++ \u00a0++ \u00a0– \u00a0+++ – Dobutamine\u00a0 \u00a0+- \u00a0– \u00a0+++ \u00a0+ \u00a0? – Dopamine \u00a0 \u00a0++ \u00a0++ \u00a0++ \u00a0+ \u00a0? +++ Dopexamine \u00a0 \u00a0– \u00a0– \u00a0+ \u00a0+++ \u00a0? ++ Isoprenaline (isoproterenol) \u00a0– \u00a0+- \u00a0+++ \u00a0+++ \u00a0+++ – Ephedrine \u00a0+ \u00a0? \u00a0++ \u00a0++ \u00a0? – Phenylephrine \u00a0 \u00a0+++ \u00a0? \u00a0– \u00a0– \u00a0– – <\/a><\/p>\n <\/p>\n Canadian Journal of Anesthesia<\/em>55:163-167 (2008)<\/p>\n Conclusion:<\/strong> Norepinephrine solutions, in concentrations commonly used in the clinical setting, are chemically stable for seven days, at room temperature and under ambient light, when diluted either in D5W or NS.<\/p>\n <\/p>\n Multicenter RCT showed dopamine associated with greater adverse event rate than norepinephrine (NEJM 2010;362:779). Subgroup analysis showed dopamine increased the risk of death in cardiogenic shock patients. Most of the adverse events were dysrhythmias.<\/p>\n <\/p>\n and Shock.<\/a> 2009 Oct 21. [Epub ahead of print]<\/p>\n Efficacy and Safety of Dopamine versus Norepinephrine in the Management of Septic Shock.<\/p>\n <\/p>\n Norepis decreases plasma volume by pushing fluid into interstium (as do prob all pressors) in septic shock (Acta Anaesthesiologica Scandinavica What is RSS?Volume 54, Issue 7, Pages 814-820)<\/p>\n <\/p>\n Norepi actually increases preload and Cardiac Output (Critical Care 2010, 14:R142<\/a>)<\/p>\n 2nd study shows similar and qualified it with PLR (Crit Care Med 2011;39:689) Also supported by older studies (J Clin Invest 1957;36:1663; J Clin Invest 1959;38:1564; J Clin Invest 1965;44:1949; Anesth 2004;100:434)<\/p>\n Norepi caused improvement in NIRS measurement of microcirc (Int Care Med 2010;36:1882)<\/p>\n MA shows norepi is superior to dopamine for septic shock (Norepinephrine or dopamine for septic shock: systematic review of randomized clinical trials. J Intensive Care Med.\u00a0 2012; 27(3):172-8 (ISSN: 1525-1489))<\/p>\n Lancet. 2007 Aug 25;370(9588):676-84.Click here to read Links Norepinephrine plus dobutamine versus epinephrine alone for management of septic shock: a randomised trial. Annane D, Vignon P, Renault A, Bollaert PE, Charpentier C, Martin C, Troch\u00e9 G, Ricard JD, Nitenberg G, Papazian L, Azoulay E, Bellissant E; CATS Study Group. Raymond Poincar\u00e9 Hospital (AP-HP), University of Versailles Saint Quentin, PRES UniverSud, Paris, France. djillali.annane@rpc.aphp.fr BACKGROUND: International guidelines for management of septic shock recommend that dopamine or norepinephrine are preferable to epinephrine. However, no large comparative trial has yet been done. We aimed to compare the efficacy and safety of norepinephrine plus dobutamine (whenever needed) with those of epinephrine alone in septic shock. METHODS: This prospective, multicentre, randomised, double-blind study was done in 330 patients with septic shock admitted to one of 19 participating intensive care units in France. Participants were assigned to receive epinephrine (n=161) or norepinephrine plus dobutamine (n=169), which were titrated to maintain mean blood pressure at 70 mm Hg or more. The primary outcome was 28-day all-cause mortality. Analyses were by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00148278. FINDINGS: There were no patients lost to follow-up; one patient withdrew consent after 3 days. At day 28, there were 64 (40%) deaths in the epinephrine group and 58 (34%) deaths in the norepinephrine plus dobutamine group (p=0.31; relative risk 0.86, 95% CI 0.65-1.14). There was no significant difference between the two groups in mortality rates at discharge from intensive care (75 [47%] deaths vs 75 [44%] deaths, p=0.69), at hospital discharge (84 [52%] vs 82 [49%], p=0.51), and by day 90 (84 [52%] vs 85 [50%], p=0.73), time to haemodynamic success (log-rank p=0.67), time to vasopressor withdrawal (log-rank p=0.09), and time course of SOFA score. Rates of serious adverse events were also similar. INTERPRETATION: There is no evidence for a difference in efficacy and safety between epinephrine alone and norepinephrine plus dobutamine for the management of septic shock.<\/p>\n This how it is used in CTICUs<\/p>\n 0.01-0.07 mcg\/kg\/min for CI at leas 2.2<\/p>\n Greet van den Berghe’s work shows neuroendocrine dysfunction as well as immunological modulation secondary to prolactin<\/p>\n (Anesth & Analg, 2004, 98,461-468)<\/p>\n Reasons Dopamine is Bad<\/p>\n Does not benefit the renal system<\/p>\n Induces Natriuresis and Diuresis<\/p>\n Shunts blood away from outer medulla, which is the region most prone to ischemic damage<\/p>\n Possible induction of decreased splanchnic perfusion<\/p>\n Decreases GI Motility<\/p>\n Impairs ventilatory response to hypoxemia and hypercapnia<\/p>\n Effects on anterior pituitary–decreases prolactin secretion<\/p>\n <\/p>\n <\/p>\n and (Holmes CL and Walley KR, Bad medicine: low-dose dopamine in the ICU, Chest, 2003, 123: 1266-1275)<\/p>\n Meta-Analysis: Low-Dose Dopamine Increases Urine Output but Does Not Prevent Renal Dysfunction or Death Jan O. Friedrich, MD, DPhil; Neill Adhikari, MD, CM; Margaret S. Herridge, MD, MPH; and Joseph Beyene, PhD Ann Intern Med 5 April 2005 | Volume 142 Issue 7 | Pages 510-524 Renal dose also causes a. fib in post op pts (Crit Care Med 2005;33:1327)<\/p>\n <\/p>\n Assoc c higher mortaility in Sepsis patients in the SOAP study:<\/p>\n Conclusions: This observational study suggests that dopamine administration may be associated with increased mortality rates in shock. There is a need for a prospective study comparing dopamine with other catecholamines in the management of circulatory shock. (Crit Care Med 2006;34(3):589)<\/p>\n measures pH of cells lining gut; based on hypothesis that CO2 in lumen of stomach or intestine in rapid equilibrium with CO2 in cells lining them; during ischemia, cells switch to anaerobic metabolism, and PCO 2 increases; splanchnic circulation believed to be first to develop ischemia; basing management on restoring gastric intramucosal pH more effective in lowering mortality than management based on hemodynamic parameters; difficult to perform; more practical new development may be noninvasive sublingual tonometry<\/p>\n No evidence that it works, may make things worse (Canadian JEM Vol. 6, No. 1, January\u00a0 2004)<\/p>\n trendelenberg does not work as shock maneuver 24. Sing R, O’Hara D, Sawyer MJ, et al. Trendelenburg position and oxygen transport in hypovolemic adults. Ann Emerg Med 1994;23:564\u0096568.Bibliographic LinksMount Sinai Serials 25. Taylor J, Weil MH. Failure of Trendelenburg position to improve circulation during clinical shock. Surg Gynecol Obstet 1967;122:1005\u00961010.Mount Sinai Serials 26. Bivins HG, Knopp R, dos Santos PAL. Blood volume distribution in the Trendelenburg position. Ann Emerg Med 1985;14:641\u0096643.Bibliographic LinksMount Sinai Serials 27. Gaffney FA, Bastian BC, Thal ER, et al. Passive leg raising does not produce a significant auto transfusion effect. J Trauma 1982;22:190\u0096193.Ovid Full TextBibliographic LinksMount Sinai Serials<\/p>\n <\/p>\n EMJ BETS (EMJ 2010;27:877) It doesn’t do squat.<\/p>\n sympathetic<\/p>\n vasopressin<\/p>\n renin\/angiotensin<\/p>\n If two are blocked then difficult to control hypotension<\/p>\n may need Vasopressin 3-5 unit IV bolus if other two systems are blocked<\/p>\n Comes in 1% 1cc vials this means 10 mg\/cc<\/p>\n Dilute in 10 cc syringe and you get 1 mg\/cc<\/p>\n Dilute again 1 cc in 10 cc and you get 100 mcg\/cc<\/p>\n give 50-100 mcg (.5-1 cc at a time) at a time<\/p>\n max 1 mg\/dose)<\/p>\n then 40-60 mcg\/min<\/p>\n <\/p>\n potent, rapid onset, short duration<\/p>\n <\/p>\n Comes in 50 mg 1 cc vial; dilute into 10 cc of NS to get 5 mg\/cc<\/p>\n 5-25 mg IV q 5-10 min<\/p>\n primarily direct beta, with some indirect alpha<\/p>\n large doses required<\/p>\n slow onset, long duration<\/p>\n <\/p>\n Peak pressor effect of phenyl 61.8 sec, peak decreased CO 30 sec<\/p>\n Ephed Peak pressor 90, peak CO 58.8<\/p>\n equivalence for map ~125:1<\/p>\n (Anesth 2009;111:753)<\/p>\n <\/p>\n 100 mg then 1-5 mg\/hr<\/p>\n synergistic with vasopressors, increased MAP, increased SVR, increased inotropy<\/p>\n Hemodynamic effects of ca as bolus and drip (<\/span>Annals of Thoracic SurgeryVolume 37, Issue 2, February 1984, Pages 133-140)<\/span><\/p>\n iCal directly correlates with arterial pressure (Crit Care Med 1988;16(6):578)<\/p>\n A randomized, blinded, placebo-controlled evaluation of calcium chloride and epinephrine for inotropic support after emergence from cardiopulmonary bypass. (Anesth Analg. 1992 Jan;74(1):3-13)<\/p>\n <\/p>\n use norepi (amrinone promising, but not enough studies (Emedhome.com article.)<\/p>\n For SBP > 80 mmHg<\/em><\/strong>, dobutamine is recommended as the initial agent of choice. It has been shown to cause less tachycardia, vasoconstriction, and arrhythmia than other agents (38,39,40)<\/em>. Additionally, dobutamine increases coronary blood flow and collateral blood flow to ischemic areas while raising myocardial contractility and cardiac output, but lowering left ventricular filling pressures (ref 39,41)<\/em>.<\/p>\n For Moderate Hypotension (e.g. SBP < 80 mmHg)<\/em><\/strong>, dopamine is recommended as the agent of choice since vasoconstriction of peripheral vessels is needed to maintain vital organ perfusion.<\/p>\n For Profound Hypotension (e.g. SBP < 70 mmHg)<\/em> or refractory hypotension<\/em><\/strong>, norepinephrine is recommended. Hemodynamic studies of acute myocardial infarction in cardiogenic shock treated with norepinephrine have shown a rise in mean arterial pressure and systemic vascular resistance. These studies also revealed improved myocardial perfusion and oxygenation, however there was no change in cardiac output. This failure to augment cardiac output is thought to represent the magnitude of the ischemic zone and lack of inotropic reserve (ref 42)<\/em>. The phosphodiesterase inhibitors, amrinone and milrinone, are known to increase contractility. They do not stimulate adrenergic receptors and play a reserve role when other catecholamines are ineffective, or when beta receptors are blocked.<\/p>\n Thrombolytics, due to poor reperfusion rates, have shown no mortality benefit in cardiogenic shock in large, randomized studies (ref 43,44)<\/em>. Intra-aortic balloon pumps decrease systemic afterload and increase diastolic perfusion pressure without increasing oxygen demands. While balloon pump use is considered standard of care, no improvement in outcome has been associated solely with its use. However, IABP does seem to function as a bridging device to revascularization. The ongoing TACTICS (thrombolysis and counterpulsation to improve cardiogenic shock survival) will address the role of IABP as an adjunct to thrombolysis (ref 45)<\/em>.<\/p>\n Vasodilating agents will increase CO, decrease PCWP; with little change in art pressure<\/p>\n at moderate and high doses there will be a decreased ABP<\/p>\n The increase in CO is seen in patients with high LV filling pressures, in normal patients the loss of filling will decrease CO b\/c of decreased starling. (Circulation 1973;48:1183)<\/p>\n <\/p>\n Cardiogenic Shock needs early revascularization (JAMA 2006;295(21):2511)<\/p>\n <\/p>\n<\/span>Pressors improve Cardiac Output<\/span><\/h2>\n
<\/span>Starling Curves<\/span><\/h3>\n
<\/span>Neligan Notes<\/span><\/h2>\n
<\/span>Low Stroke Volume<\/span><\/h3>\n
\n
<\/span>Pathophysiology<\/span><\/h2>\n
<\/span>Monitoring<\/span><\/h2>\n
JVD<\/h4>\n
<\/span>Dobutamine<\/span><\/h2>\n
<\/span>Norepinephrine<\/span><\/h2>\n
<\/span>Epinephrine<\/span><\/h2>\n
Epi as an Inotrope<\/h4>\n
<\/span>Dopamine<\/span><\/h2>\n
Gastric tonometry<\/h4>\n
<\/h4>\n
<\/span>Trendelenberg<\/span><\/h2>\n
<\/span>Three systems respond to hypotension:<\/span><\/h2>\n
<\/span>Push Dose Pressors<\/span><\/h2>\n
Phenylephrine<\/h4>\n
Ephedrine<\/h4>\n
<\/span>Calcium<\/span><\/h2>\n
<\/span>Obstructive Shock<\/span><\/h2>\n
<\/span>Decreased Diastolic Filling<\/span><\/h3>\n
Tamponade<\/h4>\n
Pneumothorax<\/h4>\n
<\/span>Increased Ventricular Afterload<\/span><\/h3>\n
Pulmonary embolism<\/h4>\n
<\/span>Cardiogenic<\/span><\/h2>\n
Cardiogenic Shock<\/h4>\n
<\/h4>\n