{"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

<\/span>Pressors improve Cardiac Output<\/span><\/h2>\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

<\/span>Starling Curves<\/span><\/h3>\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

<\/span>Neligan Notes<\/span><\/h2>\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

<\/span>Low Stroke Volume<\/span><\/h3>\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