A. Definitions

1. Syndrome caused by inadequate tissue perfusion
2. Lactic acidosis is almost uniformly present
3. Hypotension is very common

B. Clinical Symptoms

1. Hypotension
2. Tachycardia
3. Tachypnea
4. Fever
5. Anxiety
6. Confusion
7. Obtundation
8. Jugular Venous Distension (JVP, Pressure)
   1. Distinguishes preload from afterload decrease
   2. Cardiogenic shock has high preload, high JVP
   3. Septic, neurogenic and hypovolemic shock have lowpreload
   4. Invasive monitoring may be required
9. Unlikely that use of pulmonary artery catheter (PAC) improves outcome in shock [13,14]

C. Types

1. Hypovolemic (most common)
   1. Trauma
   2. Non-traumatic
2. Cardiogenic (second most common)
3. Vasodilatory (Septic)
   1. Culture Positive
   2. Culture Negative
   3. Noninfectious Vasodilatory shock: carbon monoxide poisoning, others
   4. Late stage cardiogenic and hypovolemic shock
4. Neurogenic
5. Diabetic

D. Components of the Shock Syndrome

1. Shock is defined by a state of organ hypoperfusion
2. Acute Renal Failure
   1. Renal damage due to decreased perfusion
   2. Renal endothelial inflammation contributes
   3. Tubule cells in the medulla are most suceptible to damage
   4. Acute tubular necrosis (ATN) is most common
3. Disseminated Intravascular Coagulopathy (DIC)
   1. Consumptive coagulopathy with microthrombus formation
   2. Microthrombi contribute to capillary obstruction and organ ischemia
   3. Interruption of pro-coagulant state may abrogate organ damage
4. Adult Respiratory Distress Syndrome (ARDS)
   1. Also called non-cardiogenic pulmonary edema
   2. Capillary leak syndrome in lungs due to
5. Multiorgan Failure (MOFS)
   1. Ischemia, decreased blood pressure, organ infarction
   2. Cardiac, pulmonary, renal, and hepatic failure are most common
   3. Liver is very susceptible to ischemia, but "shock liver" requires cardiac congestion [1]
   4. This shock liver accompanied by extremely high transaminase levels
   5. Kidney is almost always involved with ATN
6. Myocardial Infarction
   1. Decreased coronary perfusion due to volume loss or medications
   2. More common in patients with atherosclerotic (fixed lesions) disease
7. Cerebrovascular accident
   1. Inadequate cerebral perfusion
   2. Most common in patients with cerebrovascular disease and hypotension
8. Common Pathophysiology in Shock
   1. Activation of complement cascade and other acute inflammatory mediators
   2. Diffuse endothelial activation
   3. Abnormal platelet function

E. Pathogenesis
[Figure] "Oxygen-Hemoglobin Dissociation Curve"

1. Definition: oxygen delivery inadequate for tissue demands
   1. Delivery O2 = 1.34·CO·[Hb]·[%HbSat]
   2. Oxygen delivery also depends on affinity for hemoglobin
   3. pH, temperature, other factors affect oxygen-hemoglobin dissociation
2. Cardiac Output (CO) = Stroke Volume (SV) · Heart Rate (HR)
3. Venous Return = (PMS-PRA)÷ RV
   [Figure] "Starling Curve"
   1. PMS = mean systolic (driving) pressure
   2. PRA = pressure in right atrium
   3. RV = vascular resistance
4. Venous Return (VR) and Cardiac Output (CO) Curves intersect leads to Blood Flow
5. Distinguishing septic and cardiogenic shock [2]
   1. Pro-inflammatory mediators TNFa and IL-6 are very high in septic shock
   2. IL-6 is mildly elevated in cardiogenic shock, TNFa is normal
   3. These tests cannot distinguish mixed disorders

F. Hypovolemic Shock

1. Hemorrhage
   1. Gastrointestinal (GI) Bleeding
   2. Trauma
   3. Ruptured Pregnancy
2. Dehydration Source
   1. Gastrointestinal - diarrhea, vomiting
   2. Renal - often diuretic related, diabetes, etc.
   3. Cutaneous - fever, burns
   4. Internal - third spacing (such as pancreatitis)
3. Diagnosis [3]
   1. Clinical history is very helpful; physical exam is not sensitive
   2. Orthostatic vital sign changes are somewhat helpful
   3. Pulse increase >30 beats/min is specific but not very sensitive
   4. Capillary refill time and skin turgor are of no use in adults
   5. Serum electrolytes, renal function tests, and urine studies are most helpful
4. Management
   1. Restore Volume: crystalloid, colloid
   2. Blood needed if 10mL/kg X 3 not restore
   3. Rapid restoration leads to decreased complications
   4. Pressors utilized last (dopamine, etc)
   5. May need coagulation factors
   6. H-2 blockers if history of ulcers or ? bleeding
   7. Routine stress ulcer prophylaxisis is not required [4]

G. Cardiogenic Shock [3,5]

1. Definition
   [Figure] "Cardiogenic Shock"
   1. Decreased cardiac output and evidence of tissue hypoxia
   2. Presence of adequate intravascular volume
   3. Presence of systemic hypoperfusion ± systemic hypotension
2. Hemodynamic Criteria [3]
   1. Sustained hypotension - systolic blood pressure <90 mm Hg for at least 0.5-1.0 hour
   2. Reduced cardiac index <2.2 L/min per m2
   3. Presence of elevated pulmonary capillary occlusion (wedge) pressure >15-18 mm Hg
   4. Correction of hypoxia, acidosis and hypovolemia is required for diagnosis
   5. Systemic hypoperfusion without hypotension may be present and has poor prognosis [7]
   6. Right ventricular infarction often present in cardiogenic shock with high mortality [12]
   7. Pulmonary artery catheter (PAC) had been advocated for monitoring vital pressures
3. Clinical Signs
   1. Hypotension
   2. Oliguria / Anuria
   3. Delirium or clouded sensorium
   4. Cool, mottled extremities
4. Etiology
   1. Myocardial Infarction (MI) - occurs in 7-10% of patients after MI
   2. Cardiac Tamponade [6] - usually with acute tamponade
   3. Congestive Heart Failure (CHF)
   4. Acute mitral valve rupture
   5. Free wall or ventricular septal rupture
   6. Pulmonary Embolism leads to Cor Pulmonale
   7. Much of the cardiac dysfunction may be due to myocardial stunning and/or hibernation
5. Evaluation
   1. Organized approach with rapid diagnosis and therapy initiation
   2. Electrocardiography (ECG) for evidence of MI, tamponade, other causes
   3. Emergent echocardiography - optimal first test for evaluation
   4. Urgent or emergent cardiac angiography
   5. Use of PAC in variety of settings does not appear to improve outcomes [13,14]
   6. Frequent monitoring of renal function including urinary electrolytes
   7. Acute renal failure in setting of cardiogenic shock is very poor prognostic [11]
6. Treatment Overview
   1. Cardiogenic shock is an emergency with >50% mortality if not treated aggressively
   2. Maintain blood pressure and cardiac output (medically or with devices)
   3. Stablization with intra-aortic balloon counterpulsation may be required
   4. Relief of pain and anxiety with morphine sulfate (or fentanyl if hypotensive) may be very helpful for reducing sympathetic activity and oxygen demand [5]
   5. Emergent coronary revascularization if coronary artery disease is present [3,8]
   6. Emergent revascularization for cardiogenic shock has higher 1 and 6 year survival compared with medical stabilization followed by elective revascularization [9,15]
   7. Pericardiocentesis for cardiac tamponade [6]
   8. Thrombolysis is not effective in cardiogenic shock
   9. Prompt initiation of therapy can lead to return of stunned and hibernating myocardium
   10. Non-invasive (CPAP) or in invasive mechanical ventilation is usually required
   11. Telarginine, a nitric oxide synthase inhibitor, had no benefit in cardiogenic shock post-MI [16]
7. Revascularization
   1. Emergent cardiac catheterization is essential
   2. If not available, then stabilize and transfer patient to an appropriate facility
   3. Primary angioplasty ± stent placement may be optimal revascularizing treatment
   4. Coronary artery bypass grafting (CABG) should be used in appropriate situations
   5. At 6 months, emergent revascularization (angioplasty or CABG) group had 50.3% mortality versus 63.1% with medical therapy for cardiogenic shock [8]
   6. Thrombolysis is not very effective and should only be considered if invasive revascularization is not available
   7. Overall, strongly recommend invasive revascularization in cardiogenic shock patients [8]
8. Pharmacologic Agents
   1. Dubutamine - increased inotropy, increased chronotropy, vasodilation
   2. Amrinone / Milrinone - increased inotropy, vasodilation, little or no chronotropy
   3. Dopamine - increased inotropy; vasoconstriction at higher doses
   4. Digitalis (Digoxin) - increased inotropy but generally not used in acute setting
9. Vasodilators and afterload reducing agents should be discontinued until patient stabilized

H. Neurogenic (Distributive) Shock

1. Sympathetic Blockade
   1. Transection of sympathetic nerve tracks
   2. Peripheral vascular resistance decreased
2. Syncope common
3. Acute Korsikoff Syndrome
   1. May present with hypotension also
   2. Treat with Thiamine 100mg iv immediately
4. Loss of peripheral resistance similar to changes in septic shock

I. Vasodilatory Shock [10]
[Figure] "Septic Shock"

1. Loss of vascular tone is hallmark
2. Etiology
   1. Septic Shock
   2. Carbon monoxide poisoning
   3. Nitrogen intoxication
   4. Prolonged and severe hypotension (late stage cardiogenic and hypovolemic shock)
3. Causes of Septic Shock
   1. Gram Negative organisms - endotoxemia
   2. Gram Positive - mainly Staphylococci
   3. Fungemia - mainly candida (usually in neutropenic patients)
   4. Pancreatitis - much less common
4. Pathophysiology [10]
   1. Vasodilator overproduction and vasoconstrictor insensitivity present
   2. Nitric oxide is major vasodilator produced by endothelium and immune cells
   3. Atrial natriuretic factor (ANF), another vasodilator, also plays a role
   4. IL1ß, IL6, TNFa, many other cytokines stimulate nitric oxide production [2]
   5. Vasoconstrictor insensitivity likely due to activation of potassium channels
   6. Nitric oxide activates K(ATP) and K(Ca) channels leading to hyperpolarized endothelium
   7. Hyperpolarized endothelium is insensitive to vasoconstrictors
   8. Vasopressin (ADH) deficiency is present in vasodilatory (but not other types of) shock
5. Coagulopathy is a very common complication of septic shock

References

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2. de Werra I, Jaccard C, Corradin SB, et al. 1997. Crit Care Med. 25(4):207
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4. McGee S, Abernethy WB III, Simel DL. 1999. JAMA. 281(11):1022
5. Hollenberg SM, Kavinsky CJ, Parrillo JE. 1999. Ann Intern Med. 131(1):47
6. Spodick DH. 2003. NEJM. 349(7):684
7. Menon V, Slater JN, White HD, et al. 2000. Am J Med. 108(5):374
8. Hochman JS, Sleeper LA, Webb JG, et al. 1999. NEJM. 341(9):625
9. Hochman JS, Sleeper LA, White HD, et al. 2001. JAMA. 285(2)190
10. Landry DW and Oliver JA. 2001. NEJM. 345(8):588
11. Koreny M, Karth GD, Geppert A, et al. 2002. Am J Med. 112(2):115
12. Pfisterer M. 2003. Lancet. 362(9381):392
13. Richard C, Warszawski J, Anguel N, et al. 2003. JAMA. 290(20):2713
14. Sandham JD, Hull RD, Brant RF, et al. 2003. NEJM. 348(1):5
15. Hochman JS, Sleeper LA, Webb JG, et al. 2006. JAMA. 295(21):2511
16. TRIUMPH Investigators. 2007. JAMA. 297(15):1657