Burton Lee, MD & Sanjay Desai, MD Basics of Cardiopulmonary Critical Care II-A. Shock 1. a.

July 2009

DEFINITIONS AND PHYSIOLOGY What is shock? Shock is defined as global hypoperfusion, and is routinely (but not always) associated with hypotension and metabolic acidosis. Operationally, shocks is defined as systolic blood pressure (SBP) < 90 mm Hg or mean arterial pressure (MAP) < 60 mm Hg for at least one hour despite adequate fluid resuscitation. Clinically, patients in shock demonstrate signs of end-organ dysfunction, such as oliguria or confusion. What physiologic principles help to characterize shock? To identify the physiologic derangements causing shock in a particular situation, it is necessary to understand the determinants of mean arterial pressure. It is also necessary to understand the fundamental principles represented in the Frank-Starling curve. What are the determinants of mean arterial pressure (MAP)? Recall the pressure gradient in any circuit is determined by Ohms Law: P = Flow x Resistance. In the circulatory system, P is the difference between the upstream pressure, or MAP, and the downstream pressure, the central venous pressure (CVP). The flow is cardiac output (CO) and the resistance is the systemic vascular resistance (SVR). Therefore the relationship is: MAP CVP = CO x SVR. Additionally, CO is the product of heartrate (HR) and stroke volume (SV). Solving for MAP and accounting for units of measure, the physiologic relationship ultimately is: (units: MAP, CVP (mmHg); CO (L/min); SVR (dynes/sec/cm-5); HR (bpm); SV (L)) MAP = (CO * SVR) + CVP or MAP = (HR * SV * SVR) + CVP

b.

c.

d.

Does low blood pressure always indicate shock? As mentioned above, shock refers to a state of global tissue hypoperfusion and it is operationally defined as SBP < 90 mm Hg or MAP < 60 mm Hg, assuming there is also clinical evidence of hypoperfusion, such as mental status changes, cold extremities, oliguria, or metabolic acidosis. However, some common sense is indicated when using this definition. For example, the SBP may be <90 at baseline for some healthy individuals. If so, such individuals are probably not in shock despite the low blood pressure if there is no clinical evidence of tissue hypoperfusion. Conversely, a normal blood pressure should not be automatically equated with absence of shock. For a patient with a history of hypertension as an example, a seemingly normal MAP may represent a significant decrease in blood pressure from baseline. If so, such patients may indeed be in shock if there is evidence of tissue hypoperfusion. Therefore, blood pressure should always be interpreted in its clinical context and arbitrary values should not be automatically accepted as absolute thresholds for all patients. What is the difference between shock and specific end-organ hypoperfusion? It is important to distinguish global hypoperfusion from specific end-organ hypoperfusion. Shock refers to global end-organ hypoperfusion, where multiple organs are simultaneously under-perfused. In contrast, an embolus to the carotid artery, for example, will cause hypoperfusion of the brain (i.e. stroke) but generally not to other organs. What is the Frank-Starling curve? The Frank-Starling curve describes the relationship between preload and cardiac function. As the preload increases, the stroke volume also increases. However, as the cardiac muscle fibers become maximally stretched, the proportional increase in stroke volume decreases, causing the curve to flatten beyond a certain point. In addition to the preload, contractility of the cardiac muscles and the afterload influence the shape of this curve. For example, if a patient develops CHF, the contractility of the heart will decrease and the curve shifts downward and to the right. If so, the SV will be reduced for a given preload compared to that of a healthy patient. What are the types of shock? Given the relationship above, shock is commonly classified according to the physiologic variable that is abnormal. Common forms of shock include: Cardiogenic shock, which occurs with poor contractility or a slow heart rate (SV or HR), Distributive shock, which occurs with low afterload (SVR), and Hypovolemic shock, which occurs Page 1 of 5

e.

f.

g.

II-A: Shock

Burton Lee, MD & Sanjay Desai, MD

July 2009

with low preload (CVP or PCWP). The typical hemodynamic profiles for these conditions are summarized in the table below. 1) Cardiogenic shock (due to poor contractility): The primary abnormality is reduced contractility and a rightward shift of the Frank-Starling curve (detailed description below). The consequence of reduced contractility is decreased SV and CO. There is a compensatory increase in HR and SVR. 2) Cardiogenic shock (due to bradycardia): The primary abnormality is a slow heart rate, which reduces the CO. The SV is normal or increased, and the PCWP may be elevated. There is a compensatory increase in SVR. 3) Distributive shock: The primary abnormality is peripheral vasodilatation and reduced SVR. There is a compensatory increase in HR and CO. 4) Hypovolemic shock: The primary abnormality is reduced preload, which decreases the SV according to the Frank-Starling curve. However, unlike cardiogenic hypotension, the reduced SV is not due to poor contractility but rather to low preload. Thus, CVP, PCWP, and CO are typically reduced. There is a compensatory increase in HR and SVR.

Cardiogenic Low HR Low SV Low CO Low CO High-normal SV High PCWP High PCWP High SVR Compensatory Changes High SVR High HR Primary Abnormality Other Abnormalities

Distributive Low SVR High CO Normal SV Normal PCWP High HR

Hypovolemic Low PCWP&CVP Low CO Low SV High SVR High HR

5) Are there other causes of shock that fall outside of the classic categories above? Acute mitral regurgitation associated with rupture of chordae tendinae will decrease forward cardiac output and cause hypotension. Massive pulmonary embolism obstructs pulmonary arterial bed and will decrease forward blood flow from the right ventricle to the left atrium. In effect, the hypotension is due to reduced leftsided preload. Both pericardial tamponade and tension pneumothorax may reduce venous return to the right heart. In effect, the hypotension is due to reduced right-sided preload. The table below illustrates the hemodynamic measurements that would be consist with a variety of shock states. It also lists potential therapies for each shock state. Many of these therapies are discussed in greater detail below. Normal 70 10 70 4.9 1000 5 Cardiogenic Hypovolemia Distributive Bradycardia PE 50 50 50 50 50 20 2 10 20 2 20 20 80 80 20 2.6 2.6 10.4 1.6 1.6 1600 1600 300 1600 1600 20 1 8 20 20 - Inotropes - Volume - Pressors - Atropine - Anticoag - vol v diurese - Colloid - Volume - Pacing - Lytics - IABP/ LVAD - ?Steroids - Dopa, Isop - Extraction

MAP PCWP SV, ml CO, L/min SVR, dynes/sec/cm-5 CVP Therapies

6) How are the parameters to define shock obtained? The parameters used to characterize shock are most often those readily available at the bedside: MAP, HR, and CVP. Note that the hemodynamic profiles for various shock states use measurements available from a pulmonary artery catheter. While it is valuable to understand the use of a PAC, it is also important to recognize multiple RCTs have failed to demonstrate a mortality benefit using the PAC across a wide range of critically ill patients. As such, the use of the PAC dropped over 60% in the decade from 1996-2006. (Please see II-I: PAC and II-B: Fluid Therapy for more details). 2. a. RESUSCITATION What is the general approach to a patient with shock? CAUTION: It is important to make sure that an artifact is not the cause of the low pressure (e.g. inappropriate cuff size, or improperly zeroed or dampened arterial line). Occasionally, unilateral stenosis of a subclavian artery may Page 2 of 5

II-A: Shock

Burton Lee, MD & Sanjay Desai, MD

July 2009

reduce the blood pressure in the affected arm but systemic perfusion and the pressure in the unaffected arm may be normal. It is also important to make sure that the patient does not have a low baseline blood pressure. If this is the case, the patient should be asymptomatic and have no evidence of tissue hypoperfusion. Once clinically significant hypotension is diagnosed, the first priorities, as with any critical illness, are the ABCs, (i.e. adequacy of airway, breathing, and circulation). Following this, the underlying cause of the hypotension should be identified and addressed as quickly as possible. Reviewing the patients history, physical examination findings, laboratory results, and radiographic films are typically sufficient for correct classification of shock and initiation of resuscitative interventions. However, on some occasions, invasive assessment of CVP, PCWP, CO, and SVR may be necessary. General approaches to specific forms of shock are shown in the table below. 1) Cardiogenic shock is characterized by a reduced cardiac output due to either bradycardia or poor contractility. In general, patients with cardiogenic shock should be treated with drugs or mechanical devices that increase heartrate (if bradycardic) or enhance contractility. Inotropes (e.g. dobutamine) and vasopressors (e.g. norepinephrine) may be required in combination to overcome the vasodilatory effects of the intropic therapy. In addition, recall the Frank-Starling curve is typically shifted downward and to the right in patients with poor contractility. Thus, while these patients generally benefit from higher preload compared to other critically ill patients, their reduced contractility makes them more likely to develop pulmonary edema. If the optimal preload cannot be assessed clinically, plotting the Frank-Starling curve using a pulmonary artery catheter may be helpful. Lastly, in refractory cases, intraaortic balloon pump (IABP), left ventricular assist device (LVAD), or catheter-based assist devices can be used to augment cardiac output. Such devices can serve as temporizing measures until definitive treatment is available (e.g. CABG or transplantion). 2) Hypovolemic shock, or reduced preload, is usually characterized by a low central venous pressure (CVP). The CVP reflects preload for the right ventricle and, in most cases, the right ventricular preload accurately reflects left ventricular preload. In general, patients with hypovolemic shock should be treated with volume. Options for treatment include crystalloid fluids, colloid fluids, and packed red blood cells. It is important to note that in patients with preexisting left heart, pulmonary or right heart disease, the CVP may not accurately reflect left ventricular preload. 3) Distributive shock is characterized by a reduced systemic vascular resistance (SVR). This value can calculated only be obtaining the CVP and CO. Therefore, the diagnosis of distributive shock is routinely clinical. In general, patients with distributive shock should be treated primarily with volume resuscitation and vasopressors. The most common cause of distributive shock is sepsis. Early in sepsis or SIRS, the PCWP and CO may be low. Fever, decreased fluid intake, and third-space redistribution of fluid generally lead to hypovolemia. Thus, aggressive volume resuscitation is usually indicated during this stage, followed by vasopressor agents if volume alone does not restore adequate perfusion pressures. If adrenal insufficiency or anaphylaxis is the cause, corticosteroids should also be administered. b. Specific therapies 1) Fluids. For a more complete discussion on fluid resuscitation, please refer to II-B: Fluid Therapy and II-C: Advanced Concepts in Fluid Therapy. Below is a summary of several key concepts. a) Speed of resuscitation is important. Fluid therapy is used to restore perfusion pressure by expanding the intravascular compartment. The speed of resuscitation is important as prolonged hypoperfusion from any cause leads to increased inflammation and, ultimately, may cause distributive shock (Landry. NEJM 2001; 345: 588-95.) There are both animal and human data which suggest that delayed resuscitation worsens clinical outcome(Lee. Ann Emerg Med 2007; 49:37-44). In a large RCT of patients with severe sepsis, early goal directed resuscitation was associated with a 16% decrease in mortality (Rivers. NEJM 2001; 345: 1368-77). b) Crystalloids are preferred over colloids. The theoretical advantages of colloid in intravascular volume expansion have led to multiple studies testing its use compared with crystalloid. No studies have demonstrated a mortality benefit with colloid use, and additionally, colloids are generally more expensive than crystalloids. The largest of these studies, the SAFE trial, randomized almost 7,000 ICU patients to resuscitation with either 4% albumin or normal saline. There were no differences observed in organ failure or death (SAFE study, NEJM 2004; 350: 2247-56.). Additionally, a recent study by Brunkhorst et al. randomized over 500 patients with severe sepsis to resuscitation with lactated ringers or pentastarch. They similarly found no differences in mortality, but did observe

II-A: Shock

Page 3 of 5

Burton Lee, MD & Sanjay Desai, MD

July 2009

c)

increased risk for renal injury in those who received pentastarch (Brunkhorst, New Engl J Med 2008; 358:125-139). The optimal volume of fluid to use is challenging to determine. Ideally volume is administered until the preload is optimizedthat is, to the point where less volume would yield a lower stroke volume AND additional fluid would not increase stroke volume. The CVP and PCWP are limited in helping with this determination. There is an emerging focus on dynamic physiologic parameters that may more accurately predict optimal preload. Examples include IVC variation with respiration and pulsepressure variation. These concepts are discussed in more detail in II-C: Advanced Concepts in Fluid Therapy.

2) Vasoactive agents a) It is important to recall vasomotor physiology so that appropriate agents can be used for resuscitation. Ideally, agents should be selected for their specific vasoactive properties. The table below lists the common vasoactive receptors with their location and actions. Recpetor 1 1 2 Dopa Vasopressin Primary Location Vascular smooth muscle, (cardiac) Cardiac Vascular smooth muscle Renal, splanchnic, coronary, cerebral Vascular smooth muscle, (nephron) Primary Effect Vasoconstriction, (positive inotropy) Positive inotropy and chronotropy Vasodilation Vasodilation (low dose), Vasoconstriction (high dose) Vasoconstriction, (opens water channels)

b) Summarized below is a list of vasoactive agents that are commonly used in the ICU along with their primary effect. A more detailed discussion on vasopressors can be found in Chapter II-F: Vasoactive Therapy. Drug Dopamine Norepinephrine Phenylephrine Vasopressin Dobutamine Isoproterenol Epinephrine Nitroprusside Milrinone Activity Stimulates dopaminergic receptors at low doses. Stimulates 1 and 1 receptors at higher doses. Primarily an 1 agonist with some 1 agonist effects Almost purely an 1 agonist, but not as potent as norepinephrine Vasopressin receptors for vasopressor effects. Also is ADH released with increased osmolarity. Primarily a 1-agonist, but also has some 2agonist effects. Hence, may increase inotropy and reduce afterload. Has potent 1 and 2 effects. Infrequently used, but effective for managing bradycardia. Has potent 1, 2 and effects. Infrequently used, but effective for managing cardiogenic and anaphylactic shock. Liberates NO which causes vascular smooth muscle relaxation through cGMP PDE inhibitor increasing cAMP and augmenting LV relaxation, inotropy and vasodilation. Increased mortality with no clear benefits? rBNP causing veno and arterial dilation, naturesis and diuresis. Increased mortality? Primary Effect CO SVR SVR SVR SVR CO SVR CO SVR CO SVR CO SVR SVR Dose 1-20 ug/kg/min; titrate to effect. 2 30 g/min; titrate to effect 25 - 300 g/min; titrate to effect 0.01-0.04 units/min (physiologic levels) 2-10 g/kg/min; titrate to effect 2 g per minute and titrate to effect 1-20 g/min; titrate to effect

Niseritide

3. CONCLUSIONS. a. Determine the cause of shock: cardiogenic, hypovolemic, distributive, or other. b. Resuscitation. The current level of evidence still does not allow rigid conclusions to be drawn regarding most of the practical aspects of resuscitation. While awaiting future studies to clarify these issues, it appears prudent to: (1) always remember ABCs first, (2) treat the underlying cause of shock and tailor the resuscitative drugs and devices to the relevant form of shock; (3) aggressively volume resuscitate patients to restore hemodynamic stability as quickly as possible (i.e. MAP >65, CVP >8-12, and urine output >0.5 ml/kg/h); and (4) ideally avoid

II-A: Shock

Page 4 of 5

Burton Lee, MD & Sanjay Desai, MD

July 2009

higher preload than necessary for achieving optimal cardiac functionthis may require the use of dynamic metrics of volume status and responsiveness. Suggested Reading Book Chapters & Review Articles Marino. The ICU Book. Williams & Wilkins 2007 Third Edition. Ch. 9. The pulmonary artery catheter. pp. 163-180. Landry. The pathogenesis of vasodilatory shock. New Engl J Med. 2001;345(8);588-95.

II-A: Shock

Page 5 of 5