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CRITICAL CARE. SHOCK 1 ЯНВАРЯ 2016 Г. VITEBSK STATE MEDICAL UNIVERSITY Content Shock. General consideration.................................................................................................................. 2 Pathophysiology .................................................................................................................................. 2 Etiology and Classification ................................................................................................................... 5 Symptoms and Signs............................................................................................................................ 7 Diagnosis ............................................................................................................................................. 7 Prognosis and Treatment .................................................................................................................... 9 General management...................................................................................................................... 9 Hemorrhagic shock ........................................................................................................................ 11 Distributive shock .......................................................................................................................... 11 Cardiogenic shock.......................................................................................................................... 12 Anaphylaxis............................................................................................................................................ 14 Spinal shock and Neurogenic Shock ...................................................................................................... 18 Sepsis and Septic Shock ......................................................................................................................... 22 Cardiogenic Shock ................................................................................................................................. 29 Bradycardia and atrioventricular block ................................................................................................. 36 Tachycardias .......................................................................................................................................... 44 Sources .................................................................................................................................................. 48 1 Shock. General consideration. Shock is a state of organ hypoperfusion with resultant cellular dysfunction and death. Mechanisms may involve decreased circulating volume, decreased cardiac output, and vasodilation, sometimes with shunting of blood to bypass capillary exchange beds. Symptoms include altered mental status, tachycardia, hypotension, and oliguria. Diagnosis is clinical, including BP measurement and sometimes markers of tissue hypoperfusion (eg, blood lactate, base deficit). Treatment is with fluid resuscitation, including blood products if necessary, correction of the underlying disorder, and sometimes vasopressors. Pathophysiology The fundamental defect in shock is reduced perfusion of vital tissues. Once perfusion declines and O2 delivery to cells is inadequate for aerobic metabolism, cells shift to anaerobic metabolism with increased production of CO2 and accumulation of lactic acid. Cellular function declines, and if shock persists, irreversible cell damage and death occur. During shock, both the inflammatory and clotting cascades may be triggered in areas of hypoperfusion. Hypoxic vascular endothelial cells activate WBCs, which bind to the endothelium and release directly damaging substances (eg, reactive O2 species, proteolytic enzymes) and inflammatory mediators (eg, cytokines, leukotrienes, tumor necrosis factor [TNF]). Some of these mediators bind to cell surface receptors and activate nuclear factor kappa B (NFκB), which leads to production of additional cytokines and nitric oxide (NO), a potent vasodilator. Septic shock may be more proinflammatory than other forms of shock because of the actions of bacterial toxins, especially endotoxin. In septic shock, vasodilation of capacitance vessels leads to pooling of blood and hypotension because of “relative” hypovolemia (ie, too much volume to be filled by the existing amount of blood). Localized vasodilation may shunt blood past the capillary exchange beds, causing focal hypoperfusion despite normal cardiac output and BP. Additionally, excess NO is converted to peroxynitrite, a free radical that damages mitochondria and decreases ATP production. Blood flow to microvessels including capillaries is reduced even though large-vessel blood flow is preserved in settings of septic shock. Mechanical microvascular obstruction may, at least in part, account for such limiting of substrate delivery. Leukocytes and platelets adhere to the endothelium, and the clotting system is activated with fibrin deposition. 2 Multiple mediators, along with endothelial cell dysfunction, markedly increase microvascular permeability, allowing fluid and sometimes plasma proteins to escape into the interstitial space. In the GI tract, increased permeability possibly allows translocation of the enteric bacteria from the lumen, potentially leading to sepsis or metastatic infection. Neutrophil apoptosis may be inhibited, enhancing the release of inflammatory mediators. In other cells, apoptosis may be augmented, increasing cell death and thus worsening organ function. BP is not always low in the early stages of shock (although hypotension eventually occurs if shock is not reversed). Similarly, not all patients with “low” BP have shock. The degree and consequences of hypotension vary with the adequacy of physiologic compensation and the patient’s underlying diseases. Thus, a modest degree of hypotension that is well tolerated by a young, relatively healthy person might result in severe cerebral, cardiac, or renal dysfunction in an older person with significant arteriosclerosis. Compensation Initially, when O2 delivery (DO2) is decreased, tissues compensate by extracting a greater percentage of delivered O2. Low arterial pressure triggers an adrenergic response with sympathetic-mediated vasoconstriction and often increased heart rate. Initially, vasoconstriction is selective, shunting blood to the heart and brain and away from the splanchnic circulation. Circulating β-adrenergic amines (epinephrine, norepinephrine) also increase cardiac contractility and trigger release of corticosteroids from the adrenal gland, renin from the kidneys, and glucose from the liver. Increased glucose may overwhelm ailing mitochondria, causing further lactate production. Reperfusion Reperfusion of ischemic cells can cause further injury. As substrate is reintroduced, neutrophil activity may increase, increasing production of damaging superoxide and hydroxyl radicals. After blood flow is restored, inflammatory mediators may be circulated to other organs. Multiple organ dysfunction syndrome (MODS) The combination of direct and reperfusion injury may cause MODS—the progressive dysfunction of ≥ 2 organs consequent to life-threatening illness or injury. MODS can follow any type of shock but is most common when infection is involved; organ failure is one of the defining features of septic shock. MODS also occurs in > 10% of patients with severe traumatic injury and is the primary cause of death in those surviving > 24 h. 3 Any organ system can be affected, but the most frequent target organ is the lung, in which increased membrane permeability leads to flooding of alveoli and further inflammation. Progressive hypoxia may be increasingly resistant to supplemental O2 therapy. This condition is termed acute lung injury or, if severe, acute respiratory distress syndrome (ARDS— see Acute Hypoxemic Respiratory Failure (AHRF, ARDS)). The kidneys are injured when renal perfusion is critically reduced, leading to acute tubular necrosis and renal insufficiency manifested by oliguria and progressive rise in serum creatinine. In the heart, reduced coronary perfusion and increased mediators (including TNF and IL-1) may depress contractility, worsen myocardial compliance, and down-regulate βreceptors. These factors decrease cardiac output, further worsening both myocardial and systemic perfusion and causing a vicious circle often culminating in death. Arrhythmias may occur. In the GI tract, ileus and submucosal hemorrhage can develop. Liver hypoperfusion can cause focal or extensive hepatocellular necrosis, transaminase and bilirubin elevation, and decreased production of clotting factors. Figure 1. Compensation in shock 4 Etiology and Classification There are several mechanisms of organ hypoperfusion and shock. Shock may be due to a low circulating volume (hypovolemic shock), vasodilation (distributive shock), a primary decrease in cardiac output (both cardiogenic and obstructive shock), or a combination. Hypovolemic shock Hypovolemic shock is caused by a critical decrease in intravascular volume. Diminished venous return (preload) results in decreased ventricular filling and reduced stroke volume. Unless compensated for by increased heart rate, cardiac output decreases. A common cause is bleeding (hemorrhagic shock), typically due to trauma, surgical interventions, peptic ulcer, esophageal varices, or ruptured aortic aneurysm. Bleeding may be overt (eg, hematemesis, melena) or concealed (eg, ruptured ectopic pregnancy). Hypovolemic shock may also follow increased losses of body fluids other than blood (Hypovolemic Shock Caused by Body Fluid Loss). Hypovolemic Shock Caused by Body Fluid Loss Site of Fluid Loss Mechanism of Loss Skin Thermal or chemical burn, sweating due to excessive heat exposure GI tract Vomiting, diarrhea Kidneys Diabetes mellitus or insipidus, adrenal insufficiency, salt-losing nephritis, the polyuric phase after acute tubular damage, use of potent diuretics Intravascular fluid lost Increased capillary permeability secondary to inflammation or to the extravascular traumatic injury (eg, crush), anoxia, cardiac arrest, sepsis, bowel space ischemia, acute pancreatitis Hypovolemic shock may be due to inadequate fluid intake (with or without increased fluid loss). Water may be unavailable, neurologic disability may impair the thirst mechanism, or physical disability may impair access. In hospitalized patients, hypovolemia can be compounded if early signs of circulatory insufficiency are incorrectly ascribed to heart failure and fluids are withheld or diuretics are given. 5 Distributive shock Distributive shock results from a relative inadequacy of intravascular volume caused by arterial or venous vasodilation; circulating blood volume is normal. In some cases, cardiac output (and DO2) is high, but increased blood flow through arteriovenous shunts bypasses capillary beds; this bypass plus uncoupled cellular O2 transport cause cellular hypoperfusion (shown by decreased O2 consumption). In other situations, blood pools in venous capacitance beds and cardiac output falls. Distributive shock may be caused by anaphylaxis (anaphylactic shock); bacterial infection with endotoxin release (septic shock); severe injury to the spinal cord, usually above T4 (neurogenic shock); and ingestion of certain drugs or poisons, such as nitrates, opioids, and adrenergic blockers. Anaphylactic shock and septic shock often have a component of hypovolemia as well. Cardiogenic and obstructive shock Cardiogenic shock is a relative or absolute reduction in cardiac output due to a primary cardiac disorder. Obstructive shock is caused by mechanical factors that interfere with filling or emptying of the heart or great vessels. Causes are listed in Mechanisms of Cardiogenic and Obstructive Shock. Mechanisms of Cardiogenic and Obstructive Shock Type Mechanism Obstructive Mechanical Cause interference Tension pneumothorax, cava compression, with ventricular filling Interference cardiac tamponade, atrial tumor or clot with Pulmonary embolism ventricular emptying Cardiogenic Impaired myocardial Myocardial ischemia or MI, myocarditis, contractility Abnormalities drugs of cardiac Tachycardia, bradycardia rhythm Cardiac structural disorder Acute mitral or aortic regurgitation, ruptured interventricular septum, prosthetic valve malfunction 6 Symptoms and Signs Lethargy, confusion, and somnolence are common. The hands and feet are pale, cool, clammy, and often cyanotic, as are the earlobes, nose, and nail beds. Capillary filling time is prolonged, and, except in distributive shock, the skin appears grayish or dusky and moist. Overt diaphoresis may occur. Peripheral pulses are weak and typically rapid; often, only femoral or carotid pulses are palpable. Tachypnea and hyperventilation may be present. BP tends to be low (< 90 mm Hg systolic) or unobtainable; direct measurement by intra-arterial catheter, if done, often gives higher and more accurate values. Urine output is low. Distributive shock causes similar symptoms, except the skin may appear warm or flushed, especially during sepsis. The pulse may be bounding rather than weak. In septic shock, fever, usually preceded by chills, is typically present. Some patients with anaphylactic shock have urticaria or wheezing. Numerous other symptoms (eg, chest pain, dyspnea, abdominal pain) may be due to the underlying disease or secondary organ failure. Diagnosis Diagnosis is mostly clinical, based on evidence of insufficient tissue perfusion (obtundation, oliguria, peripheral cyanosis) and signs of compensatory mechanisms (tachycardia, tachypnea, diaphoresis). Specific criteria include obtundation, heart rate > 100, respiratory rate > 22, hypotension (systolic BP < 90 mm Hg) or a 30-mm Hg fall in baseline BP, and urine output < 0.5 mL/kg/h. Laboratory findings that support the diagnosis include lactate > 3 mmol/L, base deficit < −4 mEq/L, and PaCO2< 32 mm Hg. However, none of these findings alone is diagnostic, and each is evaluated by its trend (ie, worsening or improving) and in the overall clinical context, including physical signs. Recently, measurement of sublingual PCO2 and near-infrared spectroscopy have been introduced as noninvasive and rapid techniques that may measure the degree of shock; however, these techniques have yet to be validated on a larger scale. Diagnosis of cause Recognizing the cause of shock is more important than categorizing the type. Often, the cause is obvious or can be recognized quickly based on the history and physical examination, aided by simple testing. 7 Chest pain (with or without dyspnea) suggests MI, aortic dissection, or pulmonary embolism. A systolic murmur may indicate ventricular septal rupture or mitral insufficiency due to acute MI. A diastolic murmur may indicate aortic regurgitation due to aortic dissection involving the aortic root. Cardiac tamponade is suggested by jugular venous distention, muffled heart sounds, and a paradoxical pulse. Pulmonary embolism severe enough to cause shock typically produces decreased O2 saturation and occurs more often in special settings, including prolonged bed rest and after a surgical procedure. Tests include ECG, troponin I, chest x-ray, ABGs, lung scan, helical CT, and echocardiography. Abdominal or back pain or a tender abdomen suggests pancreatitis, ruptured abdominal aortic aneurysm, peritonitis, and, in women of childbearing age, ruptured ectopic pregnancy. A pulsatile midline mass suggests ruptured abdominal aortic aneurysm. A tender adnexal mass suggests ectopic pregnancy. Testing typically includes abdominal CT (if the patient is unstable, bedside ultrasound can be helpful), CBC, amylase, lipase, and, for women of childbearing age, urine pregnancy test. Fever, chills, and focal signs of infection suggest septic shock, particularly in immunocompromised patients. Isolated fever, contingent on history and clinical settings, may point to heatstroke. Tests include chest x-ray; urinalysis; CBC; and cultures of wounds, blood, urine, and other relevant body fluids. In a few patients, the cause is occult. Patients with no focal symptoms or signs indicative of cause should have ECG, cardiac enzymes, chest x-ray, and ABGs. If results of these tests are normal, the most likely causes include drug overdose, occult infection (including toxic shock), anaphylaxis, and obstructive shock. Ancillary testing If not already done, ECG, chest x-ray, CBC, serum electrolytes, BUN, creatinine, PT, PTT, liver function tests, and fibrinogen and fibrin split products are done to monitor patient status and serve as a baseline. If the patient’s volume status is difficult to determine, monitoring of central venous pressure (CVP) or pulmonary artery occlusion pressure (PAOP) may be useful. CVP < 5 mm Hg (< 7 cm H2O) or PAOP < 8 mm Hg may indicate hypovolemia, although CVP may be greater in hypovolemic patients with preexisting pulmonary hypertension. Rapid bedside echocardiography (done by the treating physician) to assess adequacy of cardiac filling and function is being increasingly used to assess shock. 8 Prognosis and Treatment Untreated shock is usually fatal. Even with treatment, mortality from cardiogenic shock after MI (60 to 65%) and septic shock (30 to 40%) is high. Prognosis depends on the cause, preexisting or complicating illness, time between onset and diagnosis, and promptness and adequacy of therapy. General management First aid involves keeping the patient warm. External hemorrhage is controlled, airway and ventilation are checked, and respiratory assistance is given if necessary. Nothing is given by mouth, and the patient’s head is turned to one side to avoid aspiration if emesis occurs. Treatment begins simultaneously with evaluation. Supplemental O2 by face mask is provided. If shock is severe or if ventilation is inadequate, airway intubation with mechanical ventilation is necessary. Two large (14- to 16-gauge) IV catheters are inserted into separate peripheral veins. A central venous line or an intraosseous needle, especially in children, provides an alternative when peripheral veins cannot promptly be accessed. Typically, 1 L (or 20 mL/kg in children) of 0.9% saline is infused over 15 min. In major hemorrhage, Ringer’s lactate is commonly used. Unless clinical parameters return to normal, the infusion is repeated. Smaller volumes (eg, 250 to 500 mL) are used for patients with signs of high right-sided pressure (eg, distention of neck veins) or acute MI. A fluid challenge should probably not be done in a patient with signs of pulmonary edema. Further fluid therapy is based on the underlying condition and may require monitoring of CVP or PAOP. Bedside cardiac ultrasonography to assess contractility and vena cava respiratory variability may help determine the need for additional fluid vs the need for inotropic support. Patients in shock are critically ill and should be admitted to an ICU. Monitoring includes ECG; systolic, diastolic, and mean BP, preferably by intra-arterial catheter; respiratory rate and depth; pulse oximetry; urine flow by indwelling bladder catheter; body temperature; and clinical status, including sensorium (eg, Glasgow Coma Scale), pulse volume, skin temperature, and color. Measurement of CVP, PAOP, and thermodilution cardiac output using a balloontipped pulmonary arterial catheter may be helpful for diagnosis and initial management of patients with shock of uncertain or mixed etiology or with severe shock, especially when accompanied by oliguria or pulmonary edema. Echocardiography (bedside or transesophageal) is a less invasive alternative. Serial measurements of ABGs, Hct, electrolytes, 9 serum creatinine, and blood lactate are obtained. Sublingual CO2 measurement, if available, is a noninvasive monitor of visceral perfusion. A well-designed flow sheet is helpful. Because tissue hypoperfusion makes intramuscular absorption, unreliable, all parenteral drugs are given IV. Opioids generally are avoided because they may cause vasodilation, but severe pain may be treated with morphine 1 to 4 mg IV given over 2 min and repeated q 10 to 15 min if necessary. Although cerebral hypoperfusion may cause anxiety, sedatives or tranquilizers are not routinely given. After initial resuscitation, specific treatment is directed at the underlying condition. Additional supportive care is guided by the type of shock. Figure 2. General managment 10 Hemorrhagic shock In hemorrhagic shock, surgical control of bleeding is the first priority. Volume replacement (see also Intravenous Fluid Resuscitation) accompanies rather than precedes surgical control. Blood products and crystalloid solutions are used for resuscitation; however, packed RBCs and plasma are being considered earlier and in a ratio of 1:1 in patients likely to require massive transfusion. Failure to respond usually indicates insufficient volume administration or unrecognized ongoing hemorrhage. Vasopressor agents are not indicated for treatment of hemorrhagic shock unless cardiogenic, obstructive, or distributive causes are also present. Distributive shock Distributive shock with profound hypotension after initial fluid replacement with 0.9% saline may be treated with inotropic or vasopressor agents (eg, dopamine, norepinephrine— Inotropic and Vasoactive Catecholamines). Patients with septic shock also receive broad-spectrum antibiotics (see later). Patients with anaphylactic shock unresponsive to fluid challenge (especially if accompanied by bronchoconstriction) receive epinephrine 0.05 to 0.1 mg IV, followed by epinephrine infusion of 5 mg in 500 mL 5% D/W at 10 mL/h or 0.02 mcg/kg/min (see later). Inotropic and Vasoactive Catecholamines Drug Dosage Hemodynamic Actions Norepinephrine 4 mg/250 mL or 500 mL 5% D/W α-Adrenergic: Vasoconstriction continuous IV infusion at 8–12 β-Adrenergic: mcg/min initially, then at Inotropic and 2–4 chronotropic effects* mcg/min as maintenance, with wide variations Dopamine 400 mg/500 mL 5% D/W continuous α-Adrenergic: Vasoconstriction IV infusion at 0.3–1.25 mL (250–1000 βAdrenergic: Inotropic and mcg)/min 2–10 mcg/kg/min for low chronotropic effects and dose 20 mcg/kg/min for high dose Nonadrenergic: vasodilation Renal and splanchnic vasodilation Dobutamine 250 mg/250 mL 5% D/W continuous β-Adrenergic: Inotropic effects IV infusion at 2.5–10 mcg/kg/min 11 *** *Effects are not apparent if arterial pressure is elevated too much. **Effects depend on dosage and underlying pathophysiology. ***Chronotropic, arrhythmogenic, and direct vascular effects are minimal at lower doses. Cardiogenic shock In cardiogenic shock, structural disorders (eg, valvular dysfunction, septal rupture) are repaired surgically. Coronary thrombosis is treated either by percutaneous interventions (angioplasty, stenting), coronary artery bypass surgery, or thrombolysis. Tachydysrhythmia (eg, rapid atrial fibrillation, ventricular tachycardia) is slowed by cardioversion or with drugs. Bradycardia is treated with a transcutaneous or transvenous pacemaker; atropine 0.5 mg IV up to 4 doses q 5 min may be given pending pacemaker placement. Isoproterenol (2 mg/500 mL 5% D/W at 1 to 4 mcg/min [0.25 to 1 mL/min]) is occasionally useful if atropine is ineffective, but it is not advised in patients with myocardial ischemia due to coronary artery disease. Shock after acute MI is treated with volume expansion if PAOP is low or normal; 15 to 18 mm Hg is considered optimal. If a pulmonary artery catheter is not in place, cautious volume infusion (250- to 500-mL bolus of 0.9% saline) may be tried while auscultating the chest frequently for signs of fluid overload. Shock after right ventricular MI usually responds partially to volume expansion; however, vasopressor agents may be needed. Bedside cardiac ultrasonography to assess contractility and vena caval respiratory variability can help determine the need for additional fluid vs vasopressors; inotropic support is a better approach for patients with normal or above-normal filling. If hypotension is moderate (eg, mean arterial pressure [MAP] 70 to 90 mm Hg), dobutamine infusion may be used to improve cardiac output and reduce left ventricular filling pressure. Tachycardia and arrhythmias occasionally occur during dobutamine administration, particularly at higher doses, necessitating dose reduction. Vasodilators (eg, nitroprusside, nitroglycerin), which increase venous capacitance or lower systemic vascular resistance, reduce the workload on the damaged myocardium and may increase cardiac output in patients without severe hypotension. Combination therapy (eg, dopamine or dobutamine with nitroprusside or nitroglycerin) may be particularly useful but requires close ECG and pulmonary and systemic hemodynamic monitoring. 12 For more serious hypotension (MAP < 70 mm Hg), norepinephrine or dopamine may be given, with a target systolic pressure of 80 to 90 mm Hg (and not > 110 mm Hg). Intra-aortic balloon counterpulsation is valuable for temporarily reversing shock in patients with acute MI. This procedure should be considered as a bridge to permit cardiac catheterization and coronary angiography before possible surgical intervention in patients with acute MI complicated by ventricular septal rupture or severe acute mitral regurgitation who require vasopressor support for >30 min. In obstructive shock, nontraumatic cardiac tamponade requires immediate pericardiocentesis, which can be done at the bedside. Trauma-related cardiac tamponade requires surgical decompression and repair. Tension pneumothorax should be immediately decompressed with a catheter inserted into the 2nd intercostal space, midclavicular line; a chest tube is then inserted. Massive pulmonary embolism resulting in shock is treated with anticoagulation and thrombolysis, surgical embolectomy, or extracorporeal membrane oxygenation in select cases. 13 Anaphylaxis Anaphylaxis is an acute, potentially life-threatening, IgE-mediated allergic reaction that occurs in previously sensitized people when they are reexposed to the sensitizing antigen. Symptoms can include stridor, dyspnea, wheezing, and hypotension. Diagnosis is clinical. Treatment is with epinephrine. Bronchospasm and upper airway edema may require inhaled or injected β-agonists and sometimes endotracheal intubation. Persistent hypotension requires IV-fluids and sometimes vasopressors. Etiology Anaphylaxis is typically triggered by Drugs (eg, β-lactam antibiotics, insulin, streptokinase, allergen extracts) Foods (eg, nuts, eggs, seafood) Proteins (eg, tetanus antitoxin, blood transfusions) Animal venoms Latex Peanut and latex allergens may be airborne. Occasionally, exercise or cold exposure (eg, in patients with cryoglobulinemia) can trigger or contribute to an anaphylactic reaction. History of atopy does not increase risk of anaphylaxis but increases risk of death when anaphylaxis occurs. Pathophysiology Interaction of antigen with IgE on basophils and mast cells triggers release of histamine, leukotrienes, and other mediators that cause diffuse smooth muscle contraction (eg, resulting in bronchoconstriction, vomiting, or diarrhea) and vasodilation with plasma leakage (eg, resulting in urticaria or angioedema). Anaphylactoid reactions These reactions are clinically indistinguishable from anaphylaxis but do not involve IgE and do not require prior sensitization. They occur via direct stimulation of mast cells or via immune complexes that activate complement. The most common triggers are iodinated radiopaque dye, aspirin, other NSAIDs, opioids, blood transfusions, Ig, and exercise. Symptoms and Signs Symptoms typically begin within 15 min of exposure and involve the skin, upper or lower airways, cardiovascular system, or GI tract. One or more areas may be affected, and 14 symptoms do not necessarily progress from mild (eg, urticaria) to severe (eg, airway obstruction, refractory shock), although each patient typically manifests the same reaction to subsequent exposure. Symptoms range from mild to severe and include flushing, pruritus, urticaria, sneezing, rhinorrhea, nausea, abdominal cramps, diarrhea, a sense of choking or dyspnea, palpitations, and dizziness. Signs include hypotension, tachycardia, urticaria, angioedema, wheezing, stridor, cyanosis, and syncope. Shock can develop within minutes, and patients may have seizures, become unresponsive, and die. Cardiovascular collapse can occur without respiratory or other symptoms. Late-phase reactions may occur 4 to 8 h after the exposure or later. Symptoms and signs are usually less severe than they were initially and may be limited to urticaria; however, they may be more severe or fatal. Diagnosis Diagnosis is clinical. Anaphylaxis should be suspected if any of the following suddenly occur without explanation: Shock Respiratory symptoms (eg, dyspnea, stridor, wheezing) Two or more other manifestations of possible anaphylaxis (eg, angioedema, rhinorrhea, GI symptoms) Risk of rapid progression to shock leaves no time for testing, although mild equivocal cases can be confirmed by measuring 24-h urinary levels of N -methylhistamine or serum levels of tryptase. The cause is usually easily recognized based on history. Treatment Epinephrine given immediately Sometimes intubation IV fluids and sometimes vasopressors for persistent hypotension Antihistamines Inhaled β-agonists for bronchoconstriction Epinephrine is the cornerstone of treatment; it may help relieve all symptoms and signs and should be given immediately. It can be given sc or IM (usual dose is 0.3 to 0.5 mL of a 1:1000 [0.1%] solution in adults or 0.01 mL/kg in children, repeated every 10 to 30 min). Maximal absorption occurs when the drug is given IM in the lateral thigh. Patients with cardiovascular collapse or severe airway obstruction may be given epinephrine IV in a single 15 dose (3 to 5 mL of a 1:10,000 [0.01%] solution over 5 min) or by continuous drip (1 mg in 250 mL 5% D/W for a concentration of 4 mcg/mL, starting at 1 mcg/min and titrated up to 4 mcg/min [15 to 60 mL/h]). Epinephrine may also be given by sublingual injection (0.5 mL of 1:1000 solution) or through an endotracheal tube (3 to 5 mL of a 1:10,000 solution diluted to 10 mL with saline). A second injection of epinephrine sc may be needed. Glucagon 1-mg bolus (20 to 30 mcg/kg in children) followed by 1-mg/h infusion should be used in patients taking oral β-blockers, which attenuate the effect of epinephrine. Patients who have stridor and wheezing unresponsive to epinephrine should be given O2 and be intubated. Early intubation is recommended because waiting for a response to epinephrine may allow upper airway edema to progress sufficiently to prevent endotracheal intubation and require cricothyrotomy. Hypotension often resolves after epinephrine is given. Persistent hypotension can usually be treated with 1 to 2 L (20 to 40 mL/kg in children) of isotonic IV fluids (eg, 0.9% saline). Hypotension refractory to fluids and IV epinephrine may require vasopressors (eg, dopamine 5 mcg/kg/min). Antihistamines—both H1 blockers (eg, diphenhydramine 50 to 100 mg IV) and H2 blockers (eg, cimetidine 300 mg IV)—should be given q 6 h until symptoms resolve. Inhaled βagonists are useful for managing bronchoconstriction that persists after treatment with epinephrine; albuterol 5 to 10 mg by continuous nebulization can be given. Corticosteroids have no proven role but may help prevent a late-phase reaction; methylprednisolone 125 mg IV initially is adequate. 16 Figure 3. Poster Anaphylaxis Treatment. ERC 17 Spinal shock and Neurogenic Shock Neurogenic shock is a type of distributive shock that describes the sudden loss of autonomic tone due to spinal cord injury often characterized by hypotension and relative bradycardia. Loss of sympathetic tone occurs with injuries above T6 and results in decreased systemic vascular resistance. Peripheral vasoconstrictors, chronotropes, and inotropes may be needed in cases of neurogenic shock. Autonomic instability may develop and often persists several weeks after the injury. Aggressive management is imperative in the initial phases of neurogenic shock to avoid further secondary ischemic injury to the cord. Neurogenic shock describes the sudden loss of autonomic tone due to spinal cord injury (SCI). Disruption of the descending sympathetic pathways results in unopposed vagal tone in the vascular smooth muscle, causing decreased systemic vascular resistance and vasodilation. The hypotension that results from neurogenic shock places patients at increased risk of secondary spinal cord ischemia due to impairment of autoregulation. Though the terms are sometimes used interchangeably, neurogenic shock describes the hemodynamic changes following SCI, whereas spinal shock is characterized by a reversible reduction of sensory, motor, or reflex function of the spinal cord below the level of injury(see later). Neurogenic shock is a type of distributive shock, but should be a diagnosis of exclusion in the early phases of traumatic resuscitation after hemorrhagic shock is ruled out. There is no definitive diagnostic test, but classically patients exhibit hypotension and relative bradycardia. The bradycardia is often exacerbated by suctioning, defecation, turning, and hypoxia. The skin is often warm and flushed initially. Hypothermia may develop because of profound vasodilation and heat loss. Often the central venous pressure is low due to decreased systemic vascular resistance. Thus, patients with SCI must be monitored closely for the development of neurogenic shock even if it is not present on presentation. The loss of sympathetic tone, and thus neurogenic shock, is most common when the level of the injury is above T6. Moreover, neurogenic shock may occur anytime after the onset of injury or illness, ranging from the time of presentation to several weeks after presentation. However, reports indicate anywhere from 50-90% of adults with cervical SCI require fluid resuscitation and vasoactive infusions to achieve the adult parameters recommended (MAP >85-90 mm Hg for 7 days) by the Congress of Neurological Surgeons’ guidelines for management of SCI. 18 Adults with higher SCI (C1-C5) may be more likely to require cardiovascular interventions, such as vasoactive agents or cardiac pacing, than lower (C6-C7) SCI. Decreased systemic vascular resistance results in a relative hypovolemia due to increased venous capacity, and isotonic fluid administration is often necessary. However, hypotension due to neurogenic shock is often refractory to fluid resuscitation. Nevertheless, hypotension in a trauma patient cannot be assumed to be due to neurogenic shock initially, and could be a sign of hemorrhagic shock. Thus, trauma victims with hypotension should be treated initially with crystalloid (0.9% sodium chloride, ringer’s lactate) or colloid (albumin, blood products) fluids and evaluated for any ongoing blood loss. Patients should be adequately resuscitated from a hemodynamic perspective before undergoing operative spinal cord decompression. Hypotension must be treated immediately in order to avoid secondary ischemic SCI. Cervical SCI is often seen in patients who also have traumatic brain injury and hypotension cannot be tolerated in the setting of traumatic brain injury either. Mannitol should be avoided if shock is present in patients with suspected traumatic brain and spinal cord injury, as hypertonic saline is now recommended as first-line osmotherapy agent in pediatric severe traumatic brain injury. If hypotensive patients have normal chronotropy and inotropy, then a α1-agonist acting as a peripheral vasoconstrictor such as phenylephrine is indicated. Norepinephrine may also be considered, as it has α1- and β1-agonistic activity. Epinephrine and vasopressin infusions may be used in refractory cases of hypotension. The evidence for the elevated MAP goal (MAP >85-90 mm Hg for 7 days) in adults published by the Congress of Neurological Surgeons is weak. If bradycardia is present, patients may respond to atropine, glycopyrrolate, or vasoactive infusions with chronotropic, vasoconstrictor, and inotropic properties such as dopamine or norepinephrine. Also, isoproterenol may be considered if a strictly chronotropic agent is needed. Phenylephrine can potentially cause reflex bradycardia, as there is no β agonist activity, and should be used with caution in patients with bradycardia as part of their neurogenic shock presentation. In rare cases, cardiac pacing has been successful however since the cause of the bradycardia is neurochemical rather than electrophysiological, it may be more prudent to use pharmacological treatments. If patients demonstrate particular sensitivity to suctioning or positioning, one may consider giving atropine or glycopyrrolate prior to manipulation. 19 Methylxanthines (theophylline, aminophylline) and propantheline have also been used for refractory bradycardia. Sinus bradycardia is most common in patients with severe cervical SCI, but patients may develop other dysrhythmias, including AV block, atrial fibrillation, or even cardiac arrest. Spinal Shock Spinal shock following a spinal cord injury (SCI) is a specific term that relates to the loss of all neurological activity below the level of injury. This loss of neurological activity include loss of motor, sensory, reflex and autonomic function. Spinal shock is a short-term temporary physiologic disorganisation of spinal cord function that can start between 30-60 minutes following a spinal cord injury. Spinal shock can last up to six weeks post injury. Note that the 'shock' in spinal shock does not refer to circulatory collapse, and should not be confused with neurogenic shock, which is life-threatening. Mechanism for Spinal Shock The mechanism for spinal shock involves the sudden loss of conduction in the spinal cord as a result of the migration of potassium ions from the intracellular to extracellular spaces. This is associated with a transient loss of somatic and automatic reflex activity below the level of spinal cord segment damage. The spinal cord reflex arcs that are immediately above the injury may also be severely disrupted. Early Stages of Spinal Shock Spinal shock following a spinal cord injury results in flaccid paralysis, areflexia and anaesthesia below the level of injury. The return of the reflexes indicates the end of spinal shock. Assessment of the end of spinal shock is based on the return of reflexes, with the bulbocavernosus reflex typically being the first to return. However, some clinicians may classify the end of spinal shock as the return of deep tendon reflexes or the return of reflexive detrusor function, which may be months after injury. Return of Reflexes Following Spinal Shock Return of reflexes between 4-6 weeks post injury are characterised by hyper-reflexia, or abnormally strong reflexes usually produced with minimal stimulation. Inter neurons and lower motor neurons below the SCI begin sprouting, attempting to re-establish synapses. The first synapses to form are from shorter axons, usually from inter neurons - later changes are soma-mediated, and will take longer for the soma to transport various growth factors, including proteins, to the end of the axon. 20 Autonomic Effects of Spinal Shock. In spinal cord injuries in the thoracic spinal segments of T6 and above, autonomic dysreflexia may occur, from the loss of autonomic innervation from the brain. Sacral parasympathetics (S2-S4) are lost, as are many sympathetic levels, depending on the level of the spinal cord injury. Cervical lesions cause total loss of sympathetic innervation and lead to vasovagal hypotension and bradyarrythmias – which resolve in 3–6 weeks. Autonomic dysreflexia is permanent, and occurs with the return of reflexes. Autonomic dysreflexia is characterised by unchecked sympathetic stimulation below the SCI (from a loss of cranial regulation), leading to often extreme hypertension, loss of bladder/bowel control, sweating, headaches, and other sympathetic effects. Updated guidelines issued in 2013 by the CNS and the American Association of Neurological Surgeons (AANS) recommend against the use of steroids early after an acute SCI. The guidelines recommend that methylprednisolone not be used for the treatment of acute SCI within the first 24-48 hours following injury. The previous standard was revised because of a lack of medical evidence supporting the benefits of steroids in clinical settings and evidence that high-dose steroids are associated with harmful adverse effects. Nevertheless, the administration of high-dose steroids within 8 hours of injury for all patients with acute spinal cord injury is practiced by most physicians. The current recommendation is to treat all patients with spinal cord injury according to the local/regional protocol. If steroids are recommended, they should be initiated within 8 hours of injury with the following steroid protocol: methylprednisolone 30 mg/kg bolus over 15 minutes and an infusion of methylprednisolone at 5.4 mg/kg/h for 23 hours beginning 45 minutes after the bolus. 21 Sepsis and Septic Shock Sepsis is a systemic, deleterious host response to infection leading to severe sepsis (acute organ dysfunction secondary to documented or suspected infection) and septic shock (severe sepsis plus hypotension not reversed with fluid resuscitation). Severe sepsis and septic shock are major healthcare problems, affecting millions of people around the world each year, killing one in four (and often more), and increasing in incidence. Sepsis is defined as the presence (probable or documented) of infection together with systemic manifestations of infection. Severe sepsis is defined as sepsis plus sepsis-induced organ dysfunction or tissue hypoperfusion. Sepsis-induced hypotension is defined as a systolic blood pressure (SBP) < 90 mm Hg or mean arterial pressure (MAP) < 70 mm Hg or a SBP decrease > 40 mm Hg or less than two standard deviations below normal for age in the absence of other causes of hypotension. Septic shock is defined as sepsis-induced hypotension persisting despite adequate fluid resuscitation. Sepsis-induced tissue hypoperfusion is defined as infection-induced hypotension, elevated lactate, or oliguria. Figure 4. Sepsis. Definitions and Criteria. 22 Pathophysiology of Sepsis Sepsis is induced by an invasion of microorganisms or their toxins into the bloodstream, together with the host response to this invasion. Any infection may be complicated by sepsis. The innate immune system recognizes specific molecular patterns associated with microorganisms called pathogen-associated molecular patterns (PAMPs) that include cell wall products, exotoxins, bacterial DNA, and viral RNA. The host’s innate immune system senses the presence of microbial molecules by specific receptors called pattern-recognition proteins (PRP), such as Toll-like receptors. An excessive inflammatory response early in sepsis is counteracted by an antiinflammatory response, which may then result in hypoinflammation. Hemostatic balance is shifted to a procoagulant state in sepsis due to activation of tissue factor and attenuation of natural anticoagulants. Sepsis causes endothelial dysfunction. Cardiac dysfunction in sepsis is mainly due to intramyocardial nitric oxide production and perhaps cardiac ischemia resulting in left ventricular diastolic dilatation and a rightward shift of the Frank-Starling curve. Capillary leakage causes a large amount of intravascular fluid to be shifted into the extravascular space resulting in significant hypovolemia. Sepsis is accompanied by profound arterial hypotension due to massive endothelial nitric oxide production. Microcirculatory dysfunction associated with sepsis is a result of intravascular coagulation, endothelial cell swelling, activated leukocytes, and stiff red blood cells. 23 Figure 5. Pathophysiology of Sepsis. Treatment (Surviving Sepsis Campaign. International guidelines for management of severe sepsis and septic shock. 2012) A. Initial Resuscitation 1. Protocolized, quantitative resuscitation of patients with sepsis-induced tissue hypoperfusion (defined in this document as hypotension persisting after initial fluid challenge or blood lactate concentration ≥ 4 mmol/L). Goals during the first 6 hrs of resuscitation: a) Central venous pressure 8–12 mm Hg b) Mean arterial pressure (MAP) ≥ 65 mm Hg c) Urine output ≥ 0.5 mL/kg/hr d) Central venous (superior vena cava) or mixed venous oxygen saturation 70% or 65%, respectively (grade 1C). 2. In patients with elevated lactate levels targeting resuscitation to normalize lactate. B. Screening for Sepsis and Performance Improvement 1. Routine screening of potentially infected seriously ill patients for severe sepsis to allow earlier implementation of therapy. 24 2. Hospital–based performance improvement efforts in severe sepsis. C. Diagnosis 1. Cultures as clinically appropriate before antimicrobial therapy if no significant delay (> 45 mins) in the start of antimicrobial(s) (grade 1C). At least 2 sets of blood cultures (both aerobic and anaerobic bottles) be obtained before antimicrobial therapy with at least 1 drawn percutaneously and 1 drawn through each vascular access device, unless the device was recently (<48 hrs) inserted. 2. Use of the 1,3 beta-D-glucan assay (grade 2B), mannan and anti-mannan antibody assays (2C), if available, and invasive candidiasis is in differential diagnosis of cause of infection. 3. Imaging studies performed promptly to confirm a potential source of infection. D. Antimicrobial Therapy 1. Administration of effective intravenous antimicrobials within the first hour of recognition of septic shock and severe sepsis without septic shock as the goal of therapy. 2a. Initial empiric anti-infective therapy of one or more drugs that have activity against all likely pathogens (bacterial and/or fungal or viral) and that penetrate in adequate concentrations into tissues presumed to be the source of sepsis (grade 1B). 2b. Antimicrobial regimen should be reassessed daily for potential deescalation (grade 1B). 3. Use of low procalcitonin levels or similar biomarkers to assist the clinician in the discontinuation of empiric antibiotics in patients who initially appeared septic, but have no subsequent evidence of infection (grade 2C). 4a. Combination empirical therapy for neutropenic patients with severe sepsis (grade 2B) and for patients with difficult-to-treat, multidrug-resistant bacterial pathogens such as Acinetobacter and Pseudomonas spp. (grade 2B). For patients with severe infections associated with respiratory failure and septic shock, combination therapy with an extended spectrum beta-lactam and either an aminoglycoside or a fluoroquinolone is for P. aeruginosa bacteremia (grade 2B). A combination of beta-lactam and macrolide for patients with septic shock from bacteremic Streptococcus pneumoniae infections (grade 2B). 4b. Empiric combination therapy should not be administered for more than 3–5 days. Deescalation to the most appropriate single therapy should be performed as soon as the susceptibility profile is known (grade 2B). 25 5. Duration of therapy typically 7–10 days; longer courses may be appropriate in patients who have a slow clinical response, undrainable foci of infection, bacteremia with S. aureus; some fungal and viral infections or immunologic deficiencies, including neutropenia (grade 2C). 6. Antiviral therapy initiated as early as possible in patients with severe sepsis or septic shock of viral origin (grade 2C). 7. Antimicrobial agents should not be used in patients with severe inflammatory states determined to be of noninfectious cause (UG). E. Source Control 1. A specific anatomical diagnosis of infection requiring consideration for emergent source control be sought and diagnosed or excluded as rapidly as possible, and intervention be undertaken for source control within the first 12 hr after the diagnosis is made, if feasible (grade 1C). 2. When infected peripancreatic necrosis is identified as a potential source of infection, definitive intervention is best delayed until adequate demarcation of viable and nonviable tissues has occurred (grade 2B). 3. When source control in a severely septic patient is required, the effective intervention associated with the least physiologic insult should be used (eg, percutaneous rather than surgical drainage of an abscess) (UG). 4. If intravascular access devices are a possible source of severe sepsis or septic shock, they should be removed promptly after other vascular access has been established (UG). F. Infection Prevention 1a. Selective oral decontamination and selective digestive decontamination should be introduced and investigated as a method to reduce the incidence of ventilator-associated pneumonia; this infection control measure can then be instituted in health care settings and regions where this methodology is found to be effective (grade 2B). 1b. Oral chlorhexidine gluconate be used as a form of oropharyngeal decontamination to reduce the risk of ventilator-associated pneumonia in ICU patients with severe sepsis (grade 2B). Recommendations: Hemodynamic Support and Adjunctive Therapy* G. Fluid Therapy of Severe Sepsis 1. Crystalloids as the initial fluid of choice in the resuscitation of severe sepsis and septic shock (grade 1B). 26 2. Against the use of hydroxyethyl starches for fluid resuscitation of severe sepsis and septic shock (grade 1B). 3. Albumin in the fluid resuscitation of severe sepsis and septic shock when patients require substantial amounts of crystalloids (grade 2C). 4. Initial fluid challenge in patients with sepsis-induced tissue hypoperfusion with suspicion of hypovolemia to achieve a minimum of 30 mL/kg of crystalloids (a portion of this may be albumin equivalent). More rapid administration and greater amounts of fluid may be needed in some patients (grade 1C). 5. Fluid challenge technique be applied wherein fluid administration is continued as long as there is hemodynamic improvement either based on dynamic (eg, change in pulse pressure, stroke volume variation) or static (eg, arterial pressure, heart rate) variables (UG). H. Vasopressors 1. Vasopressor therapy initially to target a mean arterial pressure (MAP) of 65 mm Hg (grade 1C). 2. Norepinephrine as the first choice vasopressor (grade 1B). 3. Epinephrine (added to and potentially substituted for norepinephrine) when an additional agent is needed to maintain adequate blood pressure (grade 2B). 4. Vasopressin 0.03 units/minute can be added to norepinephrine (NE) with intent of either raising MAP or decreasing NE dosage (UG). 5. Low dose vasopressin is not recommended as the single initial vasopressor for treatment of sepsis-induced hypotension and vasopressin doses higher than 0.03-0.04 units/minute should be reserved for salvage therapy (failure to achieve adequate MAP with other vasopressor agents) (UG). 6. Dopamine as an alternative vasopressor agent to norepinephrine only in highly selected patients (eg, patients with low risk of tachyarrhythmias and absolute or relative bradycardia) (grade 2C). 7. Phenylephrine is not recommended in the treatment of septic shock except in circumstances where (a) norepinephrine is associated with serious arrhythmias, (b) cardiac output is known to be high and blood pressure persistently low or (c) as salvage therapy when combined inotrope/vasopressor drugs and low dose vasopressin have failed to achieve MAP target (grade 1C). 27 8. Low-dose dopamine should not be used for renal protection (grade 1A). 9. All patients requiring vasopressors have an arterial catheter placed as soon as practical if resources are available (UG). I. Inotropic Therapy 1. A trial of dobutamine infusion up to 20 micrograms/kg/min be administered or added to vasopressor (if in use) in the presence of (a) myocardial dysfunction as suggested by elevated cardiac filling pressures and low cardiac output, or (b) ongoing signs of hypoperfusion, despite achieving adequate intravascular volume and adequate MAP (grade 1C). 2. Not using a strategy to increase cardiac index to predetermined supranormal levels (grade 1B). J. Corticosteroids 1. Not using intravenous hydrocortisone to treat adult septic shock patients if adequate fluid resuscitation and vasopressor therapy are able to restore hemodynamic stability (see goals for Initial Resuscitation). In case this is not achievable, we suggest intravenous hydrocortisone alone at a dose of 200 mg per day (grade 2C). 2. Not using the ACTH stimulation test to identify adults with septic shock who should receive hydrocortisone (grade 2B). 3. In treated patients hydrocortisone tapered when vasopressors are no longer required (grade 2D). 4. Corticosteroids not be administered for the treatment of sepsis in the absence of shock (grade 1D). 28 Cardiogenic Shock The clinical definition of cardiogenic shock includes decreased cardiac output and evidence of tissue hypoxia in the presence of adequate intravascular volume. The diagnosis of circulatory shock is made at the bedside by the presence of hypotension along with a combination of clinical signs indicative of poor tissue perfusion, including oliguria, clouded sensorium, and cool, mottled extremities. Hemodynamic criteria include sustained hypotension (systolic blood pressure <90 mm Hg for at least 30 minutes) and a reduced cardiac index (<2.2 L /min/m2 ) in the presence of elevated filling pressures (pulmonary capillary occlusion pressure >15 mm H g). Cardiogenic shock is diagnosed after documentation of myocardial dysfunction and exclusion or correct ion of factors such as hypovolemia, hypoxia, and acidosis. Etiology The most common cause of cardiogenic shock is left ventricular failure in the setting of an extensive acute MI , although a smaller infarct ion in a patient with previously compromised left ventricular function may also precipitate shock. Cardiogenic shock can also be caused by mechanical complications such as acute mitral regurgitation, rupture of the interventricular septum, or rupture of the free wall—or by large right ventricular infarctions. Causes of Cardiogenic Shock Acute Myocardial Infarction Pump failure Large infarction Smaller infarction with preexisting left ventricular dysfunction Infarct extension Reinfarction Infarct expansion Mechanical complications Acute mitral regurgitation due to papillary muscle rupture Ventricular septal defect Free wall rupture Pericardial tamponade Right ventricular infarction Other Conditions End- stage cardiomyopathy 29 Myocarditis Myocardial contusion Prolonged cardiopulmonary bypass Septic shock with severe myocardial depression Left ventricular out flow tract obstruct ion Aortic stenosis Hypertrophic obstructive cardiomyopathy Obstruction to left ventricular filling Mitral stenosis Left atrial myxoma Acute mitral regurgitation (chordal rupture) Acute aortic insufficiency Patients may have cardiogenic shock at initial presentation, but most do not; shock usually evolves over several hours, suggesting that early treatment may potentially prevent shock. In fact , some data indicate that early thrombolytic therapy may decrease the incidence of cardiogenic shock. Risk factors for the development of cardiogenic shock in MI generally parallel those for left ventricular dysfunction and the severity of coronary artery disease. Shock is more likely to develop in patients who are elderly , are diabetic, and have anterior MI . Pathophysiology Cardiac dysfunction in patients with cardiogenic shock is usually initiated by MI or ischemia. The myocardial dysfunction resulting from ischemia worsens that ischemia, creating a downward spiral (see Figure). When a critical mass of ischemic or necrotic left ventricular myocardium fails to pump, stroke volume and cardiac output decrease. Myocardial perfusion, which depends on the pressure gradient between the coronary arterial system and the left ventricle and on the duration of diastole, is compromised by hypotension and tachycardia, exacerbating ischemia. The increased ventricular diastolic pressures caused by pump failure reduce coronary perfusion pressure, and the additional wall stress elevates myocardial oxygen requirements, further worsening ischemia. Decreased cardiac output also compromises systemic perfusion. When myocardial function is depressed, several compensatory mechanisms are activated, including sympathetic stimulation to increase heart rate and contractility and renal fluid retention to increase preload. These compensatory mechanisms may become maladaptive and can actually worsen the situation when cardiogenic shock develops. Increased heart rate and 30 contractility increase myocardial oxygen demand and exacerbate ischemia. Fluid retention and impaired diastolic filling caused by tachycardia and ischemia may result in pulmonary congestion and hypoxia. Vasoconstriction to maintain blood pressure increases myocardial afterload, further impairing cardiac performance and increasing myocardial oxygen demand. This increased demand, in the face of inadequate perfusion, worsens ischemia and begins a vicious cycle that will end in death if not interrupted. The interruption of this cycle of myocardial dysfunction and ischemia forms the basis for the therapeutic regimens for cardiogenic shock. Figure 6. The "downward spiral" in cardiogenic shock. LVEDP - left ventricular end-diastolic pressure. Treatment Cardiogenic shock is an emergency requiring the following: Fluid resuscitation to correct hypovolemia and hypotension, unless pulmonary edema is present Prompt initiation of pharmacologic therapy to maintain blood pressure and cardiac output Admission to an intensive care setting (eg, cardiac catheterization suite or ICU or critical care transport to a tertiary care center) Early and definitive restoration of coronary blood flow; at present, this represents standard therapy for patients with cardiogenic shock due to myocardial ischemia 31 Correction of electrolyte and acid-base abnormalities (eg, hypokalemia, hypomagnesemia, acidosis) Invasive procedures include the following: Placement of a central line may facilitate volume resuscitation, provide vascular access for multiple infusions, and allow invasive monitoring of central venous pressure An arterial line may be placed to provide continuous blood pressure monitoring An intra-aortic balloon pump may be placed as a bridge to percutaneous coronary intervention (PCI, see later) or coronary artery bypass grafting (CABG, see later) Pharmacologic therapy Patients with MI or acute coronary syndrome are given aspirin and heparin Inotropic and/or vasopressor drug therapy may be necessary in patients with inadequate tissue perfusion and adequate intravascular volume, so as to maintain mean arterial pressure (MAP) of 60 or 65 mm Hg Diuretics are used to decrease plasma volume and peripheral edema Features of dopamine are as follows: Dopamine is the drug of choice to improve cardiac contractility in patients with hypotension Dopamine may increase myocardial oxygen demand Dopamine is usually initiated at a rate of 5-10 mcg/kg/min IV The infusion rate is adjusted according to the blood pressure and other hemodynamic parameters Often, patients may require doses as high as 20 mcg/kg/min Features of dobutamine are as follows: Dobutamine may be preferable to dopamine if the systolic blood pressure is higher than 80 mm Hg Compared with dopamine, dobutamine has less effect on myocardial oxygen demand Tachycardia from dobutamine may preclude its use in some patients If the patient remains hypotensive despite moderate doses of dopamine, a direct vasoconstrictor may be administered, as follows: Norepinephrine is started at a dose of 0.5 mcg/kg/min and titrated to maintain an MAP of 60 mm Hg The dose of norepinephrine may vary from 0.2-1.5 mcg/kg/min Doses as high as 3.3 mcg/kg/min have been used 32 Phosphodiesterase inhibitors (eg, inamrinone [formerly amrinone], milrinone) are inotropic agents with vasodilating properties and long half-lives that are beneficial in patients with cardiac pump failure, but they may require concomitant vasopressor administration PCI and CABG (see below) Either PCI or CABG is the treatment of choice for cardiogenic shock PCI should be initiated within 90 minutes after presentation PCI remains helpful, as an acute intervention, within 12 hours after presentation Thrombolytic therapy is second best but should be considered if PCI and CABG are not immediately available. Percutaneous coronary intervention PCI (percutaneous coronary intervention) - commonly known as coronary angioplasty or simply angioplasty, is a non-surgical procedure used to treat the stenotic(narrowed) coronary arteries of the heart found in coronary heart disease. These stenotic segments are due to the buildup of the cholesterol-laden plaques that form due to atherosclerosis. PCI is usually performed by an interventional cardiologist, though it was developed and originally performed by interventional radiologists. During PCI, a cardiologist feeds a deflated balloon or other device on a catheter from the inguinal femoral artery or radial artery up through blood vessels until they reach the site of blockage in the heart. X-ray imaging is used to guide the catheter threading. Angioplasty usually involves inflating a balloon to open the artery and allow blood flow. Stents or scaffolds may be placed at the site of the blockage to hold the artery open. Current concepts recognize that after three months the artery has adapted and healed and no longer needs the stent, which is the premise for developing stents that dissolve naturally after they are no longer necessary. 33 Figure 7. Percutaneous coronary intervention Coronary artery bypass graft Coronary artery bypass surgery, also known as coronary artery bypass graft (CABG, pronounced "cabbage") surgery, and colloquially heart bypass or bypass surgery, is a surgical procedure consisting of either diverting the left internal thoracic artery (left internal mammary artery or "LIMA") to the left anterior descending (LAD) branch of the left main coronary artery; or a harvested great saphenous vein of the leg, attaching the proximal end to the aorta or one of its major branches, and the distal end to immediately beyond a partially obstructed coronary artery (the "target vessel") - usually a 50% to 99% obstruction. The purpose is to restore normal blood flow to that partially obstructed coronary artery. It is performed to relieve angina unsatisfactorily controlled by maximum tolerated antiischemic medication, prevent or relieve left ventricular dysfunction, and/or reduce the risk of death. It does not prevent heart attacks. This surgery is usually performed with the heart stopped, necessitating the usage of cardiopulmonary bypass; however, two alternative techniques are also available allowing CABG to be performed on a beating heart either without using the cardiopulmonary bypass deemed as "off-pump" surgery or performing beating surgery using partial assistance of the cardiopulmonary bypass called as "on-pump beating" surgery. The latter gathers the advantages of the on-pump stopped and off-pump while minimizing their respective side effects. 34 Figure 8. Coronary artery bypass surgery Intra-aortic balloon pump The Intra-aortic balloon pump (IABP) is a mechanical device that increases myocardial oxygen perfusion while at the same time increasing cardiac output. Increasing cardiac output increases coronary blood flow and therefore myocardial oxygen delivery. It consists of a cylindrical polyethylene balloon that sits in the aorta, approximately 2 centimeters (0.79 in) from the left subclavia artery and counterpulsates. That is, it actively deflates in systole, increasing forward blood flow by reducing afterload through a vacuum effect. It actively inflates in diastole, increasing blood flow to the coronary arteries via retrograde flow. These actions combine to decrease myocardial oxygen demand and increase myocardial oxygen supply. Figure 9. Intra-aortic balloon pump 35 Bradycardia and atrioventricular block Classification of bradycardia and atrioventricular (AV) block Bradycardia Sinus bradycardia Junctional bradycardia Slow atrial fibrillation (distinguished from atrial fibrillation with complete AV block by variability in RR interval) Atrial flutter/atrial tachycardia with 4 : 1 AV block Complete AV block with junctional or ventricular escape rhythm Atrioventricular block First degree AV block (constant PR interval >200 ms) Second degree AV block, Mobitz type 1 (Wenckebach) Second degree AV block, Mobitz type 2 Third degree/complete AV block Causes of sinus bradycardia Cardiovascular Chronic sinus node dysfunction (due to idiopathic degenerative/fibrotic change in sinus node) Acute sinus node dysfunction due to ischemia (typically in inferior myocardial infarction; sinus node artery arises from right coronary artery in ∼90%) Maneuvers triggering high vagal tone, e.g. suctioning of airway Vasovagal syncope Carotid sinus hypersensitivity Systemic Drugs (beta-blockers, digoxin, diltiazem, verapamil, other antiarrhythmic drugs) Hypothermia Hypothyroidism Hypokalemia, hyperkalemia Raised intracranial pressure 36 Causes of atrioventricular (AV) block Acute High vagal tone (may cause Mobitz type 1 second-degree AV block, but not Mobitz type 2 or complete AV block) Myocardial ischemia/infarction Drugs (beta-blockers, digoxin, diltiazem, verapamil, other antiarrhythmic drugs) Hyperkalemia Infections: Lyme disease Myocarditis Endocarditis with abscess formation Chronic Idiopathic conducting system fibrosis Congenital complete AV block Cardiomyopathy Signs and symptoms Signs and symptoms of atrioventricular (AV) block include the following: First-degree AV block: Generally not associated with any symptoms; it is usually an incidental finding on electrocardiography Second-degree AV block: Usually is asymptomatic, but in some patients, sensed irregularities of the heartbeat, presyncope, or syncope may occur; may manifest on physical examination as bradycardia (especially Mobitz II) and/or irregularity of heart rate (especially Mobitz I [Wenckebach]) Third-degree AV block: Frequently associated with symptoms such as fatigue, dizziness, lightheadedness, presyncope, and syncope; associated with profound bradycardia unless the site of the block is located in the proximal portion of the atrioventricular node (AVN) In third-degree AV block, exacerbation of ischemic heart disease or congestive heart failure caused by AV block–related bradycardia and reduced cardiac output may lead to specific, clinically recognizable symptoms, such as the following: Chest pain Dyspnea Confusion 37 Pulmonary edema Sinus bradycardia is most often asymptomatic. However, symptoms may include the following: Syncope Dizziness Lightheadedness Chest pain Shortness of breath Exercise intolerance Treatment See Algorithm below. 38 Figure 10. Treatment of Bradycardia Transvenous and Transcutaneous Cardiac Pacing An artificial pacemaker is an electronic device that provides an electrical signal to make the heart beat when the heart's own built-in pacemaker, or conduction system, fails. The body’s anatomical, built-in pacemaker, known as the SAN (Sinoatrial) node is made up of specialized nervous tissue at the junction of the superior vena cava and the right atrium. When the SA node generates an electrical impulse, it causes the heart to contract, and the right and left atria carry the signal on to the atrioventricular (AV) node. The AV node then carries the impulse through the wiring in the ventricles, thus causing the lower chambers of the heart to 39 contract. The anatomical pacemaker provides what is called the heart’s “intrinsic” rhythm. When the internal pacemaker fails or is compromised, artificial pacemakers are appropriate therapy. There are two types of artificial pacemaker: temporary and permanent. Permanent (epicardial) pacemakers are implanted by means of a surgical procedure and are used to treat permanent conduction problems. Temporary pacemakers are used in emergency situations for transient conduction disturbances or prophylactically for anticipated dysrhythmias. Temporary pacemakers may be invasive (transvenous) or non-invasive (transthoracic). Temporary non-invasive pacemakers are typically available to clinicians as part of a cardiac resuscitation system, complete with defibrillation, cardioversion and monitoring capabilities. The two most common reasons for using temporary pacing to maintain an optimal cardiac output are when the patient has developed a symptomatic bradycardia or is asystolic. The cause for this is frequently due to impairment within the conduction system in the heart. The problem may be located within the atrioventricular (AV) node or below, within the bundle branches coursing through the ventricles. Patients can experience bradycardia as a result of several types of AV blocks. This, in turn, frequently causes decreased cardiac output. Permanent pacemakers can be implanted into these individuals to increase and maintain adequate heart rate. A second reason patients may require temporary pacing is because they are experiencing fast heart rates. Symptomatic tachycardias (rates greater than 180) may produce inadequate ventricular filling with inadequate perfusion. Some very chaotic rhythms, like ventricular fibrillation, require defibrillation. Some fast rhythms (tachycardia) are amenable to overdrive pacing by a pacemaker. These may be atrial tachydysrhythmias (atrial flutter, atrial fibrillation or atrial tachycardia) or ventricular tachycardia. This rapid rate may impair the ability of the heart to eject an adequate stroke volume. A temporary non-invasive pacemaker can be used to pace the atria at a rapid rate. If one of the pacer stimuli falls at the right time, it gains the responsibility for pacing the heart. This is known as overdrive pacing, and it either stops the tachydysrhythmia or converts the patient to a sinus rhythm. Temporary pacing can be used either on an emergency basis or to support and/or maintain an adequate heart rate for several hours or days. In some cases, the clinician uses a temporary pacemaker until the patient is stabilized and definitive care, such as a permanent implanted pacemaker, is available. 40 Non-invasive Pacemaker Functionality The non-invasive pacemaker does two things: it monitors the patient’s own intrinsic rhythm using a “sensing circuit,” and it delivers an electrical signal using an “output circuit.” If the patient’s own intrinsic rhythm becomes too slow or disappears completely, the pacemaker senses the reduction in the signal or the rate and initiates pacing through the combination pads on the patient’s chest wall. The output signals provide a regular electrical stimulus to the heart’s conduction system, signaling the heart to contract at a rate determined by the pacemaker. Pulse duration Pulse duration is the time of impulse stimulation. Early non-invasive pacemakers used short-duration (1-2 milliseconds) impulses. The action potential (electrical impulse including depolarization and repolarization) of cardiac muscle cells is longer than that for skeletal muscle, requiring 20-40 milliseconds to reach maximum effect. ZOLL found that increasing the duration from 1 to 4 milliseconds resulted in a 3-fold reduction in threshold (the current required for stimulation) to produce capture. Increasing the current from 4 to 40 milliseconds further halves the threshold. Longer durations produced no further advantage. Current ZOLL non-invasive pacemakers deliver a 40-millisecond impulse for each paced beat. This 40millisecond impulse is patented by ZOLL. Synchronous/asynchronous modes Most defibrillators have both fixed rate and synchronous pacing. Synchronous pacing is a demand mode, in which the pacer fires only when no complex is sensed for a predetermined amount of time. Pacing generally should be started in the synchronous mode to coordinate the efforts of the cardiac resuscitation system’s pacemaker with the patient’s own cardiac electrical activity. In the fixed rate (asynchronous) mode, the non-invasive pacemaker delivers an electrical stimulus at preset intervals, independent of intrinsic cardiac activity. Asynchronous pacing mode Human studies have shown that the average current necessary for external pacing is about 65-100 milliamperes (mA) in unstable bradycardias and about 50-70 mA in hemodynamically stable patients and volunteers. The clinician increases the current until the pacemaker “captures” the myocardium, taking over the pacemaker functions of the heart and resulting in a characteristic pacemaker rhythm. The clinician then confirms the presence of a 41 pulse following each pacemaker spike. The force of skeletal muscle contraction, not the electrical current, determines the patient’s level of discomfort during non-invasive pacing. Electrodes Non-invasive pacing can cause discomfort for patients and can be quite painful. Pain is a function of the current delivered per unit of skin surface area. Electrodes with a large surface area minimize pain sensation. Most commercially available electrodes are 80-100 cm2.Proper application of the external pacemaker electrodes is simple but critical. Proper skin contact is an important factor in reducing resistance and improving capture. Electrodes can be placed on the anterior chest wall, with one electrode below the right clavicle lateral to the sternum and the other electrode below the breast tissue along the midaxillary line. Electrodes can also be placed in an anteroposterior configuration with the anterior electrode placed over the precordium and the posterior electrode at the right infrascapular location. For transvenous pacing, the pacing catheter can be advanced through the brachial (antecubital), femoral, internal jugular (preferable right), subclavian (preferable left), or the right subclavian via supraclavicular access (experienced practitioner). The ECG can guide blind placement using a balloon-tipped catheter. A V1 lead of a conventional ECG is connected to the distal pole (cathode) of the pacing catheter and used to monitor a unipolar intracavitary electrogram. The catheter is floated, seeking display of intracavitary a right ventricular electrogram point at which the balloon can be deflated and the catheter advanced a few centimeters to position its tip in the right ventricular apex. Endocardial contact is confirmed by development of an “injury” current characterized by prominent ST-segment elevation. The pacing electrode is connected to the pulse generator and used in unipolar or bipolar configuration. In emergency situations when pacing is immediately required, the pacing lead may be advanced with the pulse generator on, set to its maximum output, and in the asynchronous mode at a rate of 70 to 100 ppm. Mechanical capture manifests with signs of improving cardiac output such as an increased level of consciousness or blood pressure. The clinician must monitor and assess for both electrical and mechanical capture of the myocardium. The electrical activity of the external pacer shows up clearly on the monitor as large complexes at the rate you have selected. While pacing capture on the monitor is an important sign, the appearance of these complexes does not mean that the patient’s myocardium is mechanically captured and cardiac output is occurring. 42 Skeletal muscle contraction can be uncomfortable and is often the limiting factor in non-invasive pacing use. Placing electrodes over areas of least skeletal muscle can minimize discomfort. The clinician should consider sedation if these measures are inadequate. 43 Tachycardias Vagal maneuvers to terminate tachycardia. Carotid Sinus Massage Ensure that there is no significant carotid artery disease (carotid bruits). Monitor the electrocardiogram continuously. Place the patient in the supine position with the head slightly extended. 44 Start with right carotid sinus massage. Apply firm rotatory or steady pressure to the carotid artery at the level of the third cervical vertebra for 5 sec. If no response, massage the left carotid sinus. Generally, right carotid sinus massage decreases sinus node discharge, and left carotid sinus massage slows atrioventricular conduction. Do not massage both carotids at the same time. A single application of carotid sinus pressure is effective in about 20% to 30% of patients with paroxysmal supraventricular tachycardias; multiple applications terminate tachycardia in about 50% of patients. Asystole is a potential but rare complication. Valsalva Maneuver Valsalva maneuver involves an abrupt voluntary increase in intrathoracic and intraabdominal pressures by straining. Monitor the electrocardiogram continuously. Place the patient in the supine position. The patient should not take a deep inspiration before straining. Ideally, the patient blows into a mouthpiece of a manometer against the pressure of 30-40 mm Hg for 15 sec. Alternatively, the patient strains for 15 sec while breath-holding. Transient acceleration of tachycardia usually occurs during the strain phase as a result of sympathetic excess. On release of strain, the rate of tachycardia slows because of the compensatory increase in vagal tone (baroreceptor reflex); it may terminate in about 50% of patients. Termination of tachycardia may be followed by pauses and ventricular ectopics. 45 Cardioversion DC-cardioversion (DCC) Cardioversion is a synchronized administration of shock during the R waves or QRS complex of a cardiac cycle. During defibrillation and cardioversion, electrical current travels from the negative to the positive electrode by traversing myocardium. It causes all of the heart cells to contract simultaneously. This interrupts and terminates abnormal electrical rhythm. This, in turn, allows the sinus node to resume normal pacemaker activity. Tachyarrhythmias that do not respond to medical treatment or that are associated with hemodynamics compromise (e.g. hypotension, worsening heart failure) may be converted to sinus rhythm by the use of a transthoracic electric shock. A short-acting general anaesthetic is used. Musclerelaxants are not usually given. When the arrhythmia has definite QRS complexes, the delivery of the shock should be timed to occur with the downstroke of the QRS complex (synchronization). The machine being used to perform the cardioversion will do this automatically if the appropriate button is pressed. There is a crucial 46 difference between defibrillation and cardioversion: a non-synchronized shock is used to defibrillate. Accidental defibrillation of a patient who does not require it may itself precipitate ventricular fibrillation. Typical indications for cardioversion include: atrial fibrillation atrial flutter sustained ventricular tachycardia junctional tachyarrhythmias. If atrial necessary fibrillation or flutter has been present for more than a few days, it to anticoagulate is the patient adequately for 3 weeks before elective cardioversion to reduce the risk of embolization. The duration of anticoagulation after successful cardioversion for atrial fibrillation is a complex issue and depends on a number of factors: it should be for at least 4 weeks after the procedure and may well befor much longer. Digoxin toxicity may lead to ventricular arrhythmias or asystole following cardioversion. Therapeutic digitalization does not increase the risks of cardioversion, but it is conventional to omit digoxin several days prior to elective cardioversion in order to be sure that toxicity is not present. Cardiac enzyme levels may rise after a cardioversion. Cardioversion Defibrillation Elective planned procedure Emergency life-saving procedure Synchronized Shock UN-Synchronized Shock Low energy shock High energy shock There can be some delay No delay, immediate Anti-coagulation needed No anti-coagulation needed Less damage to myocardium More damage to myocardium Used in most of the arrhythmias except Used in VT/VF VT/VF 47 Sources 1. John F. Butterworth IV, David C. Mackey, John D. Wasnick - Morgan & Mikhail’s Clinical Anesthesiology. 5th Edition - Copyright © 2013, 2006, 2002 by McGraw-Hill Education, LLC. 2. Agamemnon Despopoulos, Stefan Silbernagl - Color Atlas of Physiology - © 2003 Thieme 3. C.A. Vacanti - Essential clinical anesthesia - © 2011 - Cambridge University Press 4. Joseph E. Parrillo, R. Phillip Dellinger - Critical Care Medicine. Principles of Diagnosis and Management in the Adult. 4th Edition. - © 2014 by Saunders, an imprint of Elsevier Inc 5. International Guidelines for Management of Severe Sepsis and Septic Shock: 2012 6. Parveen Kumar - Clinical Medicine. Seventh Edition.- © 2009, Elsevier Limited. 48