Shock

Shock:

Failure of the circulatory system to maintain adequate cellular (tissue) perfusion and function. Inadequate tissue perfusion results in

decreased tissue oxygen delivery and an imbalance between tissue oxygen supply and oxygen demand, resulting in lactic acidosis. Impaired blood flow to vital organs and tissues. Based on the predominant physiologic derangement,

4 Types and Causes of Shock States:

1. Hypovolemic shock from inadequate circulating volume. Adrenal crisis. Hemorrhage. Severe dehydration.

• Hemorrhage is a leading cause of preventable trauma death. Acute resuscitation protocols increasingly advocate early transfusion of blood components at a 1:1:1 ratio of packed red blood cells, fresh frozen plasma, and platelets, but the latter products may require 30 minutes to prepare, even for emergency use.

2. Cardiogenic shock from inadequate cardiac pump function (inadequate pump function): Cardiac rupture. Congestive heart failure. Dysrhythmia. Intracardiac shunt (e.g., septal defect). Ischemia/infarction. Myocardial contusion. Myocarditis. Valvular dysfunction.

3. Distributive (vasogenic, neurogenic) shock from massive peripheral vasodilatation (misdistrubution of the circulating volume). Adrenal crisis. Anaphylaxis. Capillary leak syndromes. Neurogenic. Sepsis. Toxicologic.

4. Obstructive shock from extracardiac obstruction to blood flow (mostly from PE). Air embolism. Cardiac tamponade. Massive pulmonary embolus. Tension pneumothorax.

Ddx: “SHOCK“: Sepsis, Hypovolemia, Other (Addison’s, drugs), CNS(spinal shock), “K” cardiogenic (MI).

Anaphylaxis –> DOC (drug of choice) is Epi. See skin eruptions and large welts. Localized edema, especially around the face. Weak and rapid pulse. Breathlessness and cough due to narrowing of airways and swelling of the throat. See Anaphylaxis |

Massive PE or TCA OD –> drug of choice (DOC) is NE.

S/s: The presence of shock is best detected by looking for evidence of compromized end organ perfusion. In profound shock other autonomic mechanisms, primarily vagal, may come into play. Most easily detected in the skin as central pallor, peripheral cyanosis, and sluggish capillary return. In the presence of low cardiac filling pressures in severe hypovolemia, tachycardia may be replaced with a reflex bradycardia. As shock progresses, cells in ischemic tissues switch to anaerobic metabolism and lactic acidosis stimulates compensatory hyperventilation. Along with raised respiratory rate, see confusion / coma, diminished urine output (renal hypoperfusion), cardiac ischemia on ECG and metabolic (lactic) acidosis on ABG. Pulse rates and BP can be normal, high or low. Shock cannot be excluded solely on the basis of normal vital signs.

Shock index (SI): defined as the heart rate divided by the systolic blood pressure (HR/SBP). Normal values range from 0.5 to 0.7. The risk for massive transfusion doubles with a SI > 0.9, quintuples for SI > 1.1, and was 7 times higher for SI > 1.3. Reliably predicts the need for massive transfusion in blunt trauma patients and is probably valid for penetrating injury as well. The prehospital shock index — a measurement obtained while the patient is en route to a trauma center — can predict the need for emergency blood transfusion (Anesthesiology 2012: American Society of Anesthesiologists (ASA) Annual Meeting. Abstract A649. Presented October 14, 2012).

Historical clues in shock states:

Preceding chest pain – Cardiogenic.

Shortness of breath – Obstructive.

Orthopnea – Cardiogenic.

Any new medication – Distributive (anaphylactic).

Vomiting and diarrhea – Hypovolemic.

Hemorrhage – Hypovolemic.

Rash – Distributive (anaphylactic, septic).

Intravenous drug use – Distributive (septic) or Cardiogenic.

Indwelling devices (catheters, lines) – Distributive (septic).

Chronic debility/neurologic disease – Distributive (septic) or Hypovolemic.

Trauma – Hypovolemic (hemorrhage).

Clinical parameters in the Dx of shock:

Heart rate: Tachycardia (HR >100 in non-pregnant adults) is present in most patients with shock; however, its presence may be masked by multiple factors including spinal cord injury, medications, intra-abdominal catastrophe, older age and cardiac conduction abnormalities.

Blood pressure: Hypotension (arbitrarily systolic BP <90) is a late finding in shock. In early shock, it may actually be transiently elevated. Measurements, in particular with standard BP cuff, become less accurate in shock states. A narrow pulse pressure may be present in hypovolemic shock. A wide pulse pressure may be seen in distributive shock.

Shock index: Heart rate/systolic blood pressure. An index of >0.9 is a more sensitive indicator of shock than either blood pressure or heart rate alone.

Pulsus paradoxus: A wide variation of blood pressure with respiration (>10 mm Hg) may indicate obstructive shock (e.g., cardiac tamponade) Respirations: Either high (>24/min) or low (<12/min) rates may suggest a shock state, as may very shallow or deep breathing.

Skin signs: Cool and clammy skin is often an indicator of a shock state although certain distributive shock states may have warm and dry skin (neurogenic and early septic shock). Delayed capillary refill (>2 seconds) is another sign of shock.

Urine output: Most often reduced (<30 ml/h) in shock states.

Presentation of Pediatric Shock: Clinical signs of shock in children vary with age (Pediatr Emerg Care 2010;26:622)…..of 147 patients, the most common category of shock was septic (57%), followed by hypovolemic (24%), distributive (14%), and cardiogenic (5%)……Most patients (71%) with delayed shock were younger than 2 years…..Seven patients without initial signs of shock presented with tachycardia with normal perfusion; six of these patients were older than 10 years…..younger patients (36 months) more often exhibiting poor perfusion or weak pulses and older patients more likely to have hypotension…..Compensatory mechanisms, such as increased cardiac contractility and peripheral vascular resistance, vary with age in children. Older children present similarly to adults, whereas infants and toddlers might simply look ill or exhibit poor perfusion and not have the hypotension that is the hallmark of shock in older children.

Distributive (Vasodilatory) Shock: most due to Sepsis | Other causes include inadequate tissue oxygenation (nitrogen intoxications with hypoxic lactic acidosis), prolonged severe hypotension (hemorrhagic or cardiogenic shock, cardiopulmonary bypass), shock with probable vasodilation (Metformin intoxication, some mitochondrial dz’s, cyanide poisoning, cardiac arrest with PEA), may also be seen in anaphylaxis, liver failure or glucocorticoid def (NEJM 2001;345:8).

Septic: Link: Sepsis | Vasopressin | Vasopressors |

50% due to G-, 25% G+, from endotoxemia that leads to vascular collapse and multiple organ failure. Hypotension from vasodilators (lipopolysaccharide, TNF, C3a, C5a). Positive blood Cx in <50%. Hypotension, mildly incr HR, warm, pink, wide pulse pressure. Initial tx is an attempt to eradicate the infection via Abx + surgical drainage. If severe met acidosis (pH <7.2) consider bicarb. Use Dobutamine + Norepinephrine (Levophed) or Epinephrine. In cases of septic shock where the desired vasoconstriction is not achieved by a dopamine infusion norepinephrine can be added as a second drug. Epinephrine alone and norepinephrine plus dobutamine had similar efficacy and safety in a multicenter RCT on Vasopressor’s in septic shock (Lancet 2007;370:636-7)….editorialist notes that “if simplicity is best, then using one drug (epinephrine) over two creates less opportunity for error”….Epinephrine has been shown to have deleterious effects on splanchnic blood flow and acid-base balance compared with norepinephrine, but these effects are transientr.

Phenylephrine @ 20-200 mcg/min (pure alpha-1 agonist) has a theoretical advantage as it maintains a near normal gastric pH. Dopamine is often used, but may not be as efficacious at reversing the hemodynamic abnormalities.

Neurogenic Shock: Triad of hypotension, bradycardia and hypothermia. Decr symp tone leads to a decr BP, HR and pulse pressure, no vasoconstriction possible. Neurogenic shock occurs when an acute spinal cord injury disrupts sympathetic flow, resulting in hypotension and bradycardia. Typically seen in two arenas: the trauma resuscitation bay and the operating room. Traumatic spinal injury occurs when the cord is severed at a level within or above the sympathetic chain, whereas neurogenic shock encountered in the operating room is the consequence of a neuraxial anesthetic that has extended beyond its intended effect. The heart also receives sympathetic input, there is an important functional distinction between an injury above T-4 and one below T-4. The former depresses cardiac function in addition to affecting venous return, whereas the latter leaves cardiac performance unaffected.

S/s: similar to hypovolemic shock except in the skin’s characteristics. In neurogenic shock, the skin is warm and dry.

Tx: Therapy is aimed at mitigating hypotension and bradycardia, crystalloid should be infused with a goal mean arterial pressure >70 mm Hg. If inotropic support is necessary, the use of dobutamine or dopamine (both dosed at 2-20 mcg/kg/min). Dopamine is the drug of choice. For symptomatic bradycardia, atropine should be used. In pt’s who develop heart block or asystole, a pacemaker may be necessary. Steroids for spinal cord injury. When cardiac performance is unaffected, limited volume resuscitation and tx with a pure a-agonist such as phenylephrine is sufficient therapy. However, if the cardiac sympathetic innervation is compromised, vagal parasympathetic innervation may predominate and administration of phenylephrine may aggravate reflex bradycardia. To preclude this undesirable effect of therapy, a mixed inotrope and chronotrope such as dopamine or norepinephrine is used. In extreme cases, temporary cardiac pacing may be lifesaving. Volume restoration is also required. If caused by sepsis the infection is treated with antibiotics and supportive care is given (inotropics, mechanical ventilation, renal function replacement). Anaphylaxis is treated with adrenaline to stimulate cardiac performance and corticosteroids to reduce the inflammatory response. In neurogenic shock because of vasodilation in the legs, one of the most suggested treatments is placing the patient in the Trendelenburg position, thereby elevating the legs and shunting blood back from the periphery to the body’s core. However, since bloodvessels are highly compliant, and expand as result of the increased volume locally, this technique does not work. More suitable would be the use of vasopressors. See General Tx of Shock |

Endocrine Shock: Adrenal insufficiency is important to consider because it is often not rapidly identified. In patients with Addison’s disease, the lack of cortisol decreases the activity of catecholamines and angiotensin, which decreases their ability to increase SVR in the setting of volume depletion. Also, cortisol normally decreases activity of TNF alpha, a potent vasodilator, so increased activity of TNF also contributes to a decrease in SVR. Lack of aldosterone further contributes to hypovolemia due to sodium depletion. Usually, shock is precipitated by an acute stressful event such as infection or surgery. Prior symptoms may include fatigue and abdominal pain.

Hypothyroidism: in critically ill patients, reduces cardiac output and can lead to hypotension and respiratory insufficiency. There may be a previous history of thyroid disease or pernicious anemia suggesting polyglandular autoimmune disease.

Thyrotoxicosis: may induce a reversible cardiomyopathy.

Acute adrenal insufficiency: frequently the result of discontinuing corticosteroid treatment without tapering the dosage. However, surgery and intercurrent disease in patients on corticosteroid therapy without adjusting the dosage to accommodate for increased requirements may also result in this condition. Increased skin pigmentation may be noted due to an increased adrenocorticotropic hormone (ACTH) level (which stimulates melanocytes). Patients with Addison’s disease will often have hyponatremia, hyperkalemia, metabolic acidosis, and eosinophilia (due to decreased cortisol levels). If Addison’s disease is suspected, an ACTH stimulation test is indicated—measure ACTH, cortisol and aldosterone levels at baseline, and measure cortisol and aldosterone again 30 minutes after ACTH administration. If Addison’s disease is present baseline levels of cortisol and aldosterone will be low with high ACTH levels, and cortisol and aldosterone levels will not increase after ACTH administration. Patients may also present with an isolated glucocorticoid deficiency, most commonly from chronic glucocorticoids suppressing endogenous cortisol production. These patients still make mineralocorticoids through the renin-angiotensin system. When the patient is stressed due to surgery or infection there may be an inadequate cortisol production. They will be hypotensive secondary to a decrease in SVR related to isolated glucocorticoid deficiency. Patients with isolated glucocorticoid deficiency may have hyponatremia, but should not be hyperkalemic since the reninangiotensin-aldosterone system is intact.

Relative adrenal insufficiency: critically ill patients where present hormone levels are insufficient to meet the higher demands

Tx: In endocrine shock the hormone disturbances are corrected. Hypothyroidism requires supplementation by means of levothyroxine, in hyperthyroidism the production of hormone by the thyroid is inhibited through thyreostatica, i.e. methimazole (Tapazole) or PTU (propylthiouracil). Adrenal insufficiency is treated by supplementing corticosteroids. See General Tx of Shock |

Cardiogenic Shock: This type of shock is caused by the failure of the heart to pump effectively. This can be due to damage to the heart muscle, most often from a large myocardial infarction. Commonly seen with >35% loss of functioning of LV after an AMI. Other causes of cardiogenic shock include arrhythmias, cardiomyopathy, CHF, contusio cordis or cardiac valve problems. Get decr CO and lactic acidosis due to tissue hypoxia. MR occurs frequently with inferoposterior MI, a ruptured LV wall may occur. See Cardiogenic Shock |

Criteria: SBP <90 mmHg (higher if chronic HTN), UO <0.5ml/kg/hr, evidence of end-organ damage (renal failure, confusion, cool extremities), if hemodynamic monitor will see a PCWP >18 mmHg and a CI of <1.8 L/min/m2).

S/s: similar to hypovolemic shock (see below) but in addition: Distended jugular veins due to increased jugular venous pressure. Absent pulse due to tachyarrhythmia. Obstructive shock, similar to hypovolaemic shock but in addition: Distended jugular veins due to increased jugular venous pressure. Pulsus paradoxus in case of tamponade.

W/u: ECG consistent with AMI (right-sided leads should be performed if posterior wall infarction is suspected). CXR for evidence of CHF, abnormal mediastinum, and evaluation of the cardiac silhouette. Echo-cardiography done at the bedside can quickly evaluate regional hypokinesis, akinesis, or dyskinesis. Lab studies including cardiac enzymes, coagulation parameters, serum lactate, BNP and chemistries.

Tx: See General Tx of Shock | Vasopressors | During Tx aim for a LV filling pressure of 15-18 mmHg and CI of >2.2 L/min/M2. Start vasopressors and inotropic agents if SBP low despite fluids. Inotropic agents, which enhance the heart’s pumping capabilities, are used to improve the contractility and correct the hypotension. Should that not suffice, an intra-aortic balloon pump can be considered (which reduces the workload for the heart and improves perfusion of the coronary arteries) or a left ventricular assist device (which augments the pump-function of the heart). The main goals of the treatment of cardiogenic shock are the re-establishment of circulation to the myocardium, minimising heart muscle damage and improving the heart’s effectiveness as a pump. This is most often performed by percutaneous coronary intervention and insertion of a stent in the culprit coronary lesion or sometimes by cardiac bypass. Although this is a protection reaction, the shock itself will induce problems; the circulatory system being less efficient, the body gets “exhausted” and finally, the blood circulation and the breathing slow down and finally stop (cardiac arrest). The main way to avoid this deadly consequence is to make the blood pressure rise again with fluid replacement with intravenous infusions; use of vasopressing drugs (e.g. to induce vasoconstriction); use of anti-shock trousers that compress the legs and concentrate the blood in the vital organs (lungs, heart, brain).

The nitric oxide synthase (NOS) inhibitor tilarginine (ArgiNOx Pharmaceuticals) had no effect on mortality in pt’s with refractory cardiogenic shock complicating MI (TRIUMPH study. JAMA. 2007;297:000-000:online March 26).

Hypovolemic Shock: Seen with loss of >40% of the circulating blood volume. Hypotension, profound tachycardia. Usually due to bleeding, severe diarrhea or emesis, burns, or redistribution of body fluids. The diagnosis of nonhemorrhagic hypovolemic shock is usually readily apparent from the history of gastrointestinal losses (vomiting and/or diarrhea), fluid losses (increased urine output due to diabetes, diuretics), or insensible losses (burn patients). See Dehydration and Hypovolemia |

S/s: Anxiety, restlessness, altered mental state due to decreased cerebral perfusion and subsequent hypoxia. Hypotension due to decrease in circulatory volume. A rapid, weak, thready pulse due to decreased blood flow combined with tachycardia. Cool, clammy skin due to vasoconstriction and stimulation of vasoconstriction. Rapid and shallow respirations due to sympathetic nervous system stimulation and acidosis. Hypothermia due to decreased perfusion and evaporation of sweat. Thirst and dry mouth, due to fluid depletion. Fatigue due to inadequate oxygenation. Cold and mottled skin (cutis marmorata), especially extremities, due to insufficient perfusion of the skin. Distracted look in the eyes or staring into space, often with pupils dilated. May see dry mucous membranes and poor skin turgor. Evidence of prerenal azotemia with BUN/ Cr ratio >20. Hemorrhagic shock is often apparent due to history of hematochezia, hematemesis, or melena, although sometimes blood loss may be occult (into the retroperitoneum, the thigh, or the chest). In addition, in patients with acute gastrointestinal hemorrhage, the initial hematocrit may not be low if enough time has not elapsed for equilibration. In shock BP is usually <70mmHg. If can feel radial pulse–> BP must be at least 80-90mmHg. Femoral–> 70mmHg. Carotid only–> 50mmHg. Metabolic acidosis (mainly due to lactic acid) accumulates as a result of poor delivery of oxygen to the tissues, and mirrors the severity of the shock. It is best treated by rapidly restoring intravascular volume and perfusion as above.

Tx: Key tx if fluid resuscitation. As soon as the airway is maintained and oxygen administered the next step is to commence replacement of fluids via the IV route. If caused by bleeding, it is necessary to immediately control the bleeding and restore the casualty’s blood volume by giving infusions of isotonic crystalloid solutions. Blood transfusions, packed red blood cells (RBCs), Albumin (or other colloid solutions), or fresh-frozen plasma are necessary for loss of large amounts of blood (>20% of blood volume), but can be avoided in smaller and slower losses. Hypovolemia due to burns, diarrhea, vomiting, etc. is treated with infusions of electrolyte solutions that balance the nature of the fluid lost. Sodium is essential to keep the fluid infused in the extracellular and intravascular space whilst preventing water intoxication and brain swelling. Inotropic and vasoconstrictive drugs should be avoided, as they may interfere in knowing blood volume has returned to normal. See General Tx of Shock |

A study with 921 patients with blunt injury post-traumatic hemorrhagic shock found that the use of vasopressors (Levophed, phenylephrine, dopamine, or vasopressin) within 12 hours after injury, compared with no use of vasopressors, was associated with an increased mortality risk (hazard ratio, 1.81), as was use of vasopressors within 24 hours after injury (HR, 2.15) (J Trauma 2008;64:9)…..Aggressive early crystalloid resuscitation within 12 hours, compared with no use of crystalloid resuscitation, was associated with a reduction in mortality (HR, 0.59). Crystalloid resuscitation is a mainstay in the management of post-traumatic hemorrhagic shock, but excessive fluid administration might increase or aggravate coagulopathy, abdominal compartment syndrome, pulmonary and cardiac dysfunction, gastrointestinal ileus, and bowel anastomotic complications. Smaller IVC diameter on U/S (mean, 6.5 vs. 10.7 mm & IVC diameter multiplied by body-mass index; mean, 143.6 vs. 218.1) after initial resuscitation indicates inadequate volume status / hypovolemic shock (J Trauma 2007;63:1245)…..significantly greater proportion of patients who underwent emergent hemostatic procedures (47% vs. 7.6%) and a higher mortality rate (30% vs. 0%).

Hemorrhagic Shock: Due to bleeding (internal or external). Tx by stopping the bleeding, fluids and replacement of blood. Patients in hemorrhagic shock can be successfully resuscitated with human polymerized hemoglobin (PolyHeme) with no increase in mortality and with a reduced need for blood transfusions according to a phase III multicenter study (J Am Coll Surg 2009;208:1-13)…..PolyHeme, made from human blood, “has a half life of approximately 24 hours and is gone in 72 hours.

Obstructive Shock

Obstruction to venous return is a surgical emergency. Usually has a vascular etiology. Consider aortic stenosis, PE or tamponade from tension pneumo–> incr HR, decr heart sounds, distended neck veins, +pulsus paradoxus (decr SBP >10 during insp), Kussmaul’s sign (incr venous pressure with insp). The two common causes encountered by general surgeons are pericardial tamponade and tension pneumothorax; obstetricians encounter a similar physiologic effect when the gravid uterus presses on the inferior vena cava. All abdominal surgeons occasionally cause transient obstructive shock by pressing on the inferior vena cava during surgery. Pulmonary embolism and air embolism are the other two major causes of obstructive shock. Analysis of tension pneumothorax according to Guyton’s principles, the venous return curve is markedly distorted because the pleural pressure exceeds the right atrial pressure. Venous return no longer depends on the arithmetic difference between Pms and right atrial pressure, but on the difference between Pms and (the very positive) pleural pressure. The cardiac function curve is also adversely affected by two mechanisms. The rightward shift occurs because the transmural filling pressure is zero when the right atrial pressure falls to the (now positive) value of the pleural pressure. The downward pivot of the cardiac function curve is caused by a reflex increase in pulmonary vascular resistance. Although there is an endogenous catecholamine surge, it is apparent from the analysis that neither a volume load nor administration of exogenous catecholamines will have a significant effect on circulation. The only effective therapy is immediately to reduce pleural pressure by relieving the tension pneumothorax. Pericardial tamponade provides a nearly identical analysis, except that the limitation on transmural pressure is not pleural pressure but pericardial pressure.

Tx: In obstructive shock, the only therapy consists of removing the obstruction. Pneumothorax or haemothorax is treated by inserting a chest tube, pulmonary embolism requires thrombolysis (to reduce the size of the clot), or embolectomy (removal of the thrombus), tamponade is treated by draining fluid from the pericardial space through pericardiocentesis.

Labs: CBC, lytes, blood sugar, lactate, UA, ECG, CXR. If bleeding get T&C.

All pt’s should be given high flow oxygen, have IV access secured, and have basic monitoring instituted (non-invasive blood pressure, pulse oximetry, and continuous ECG).

Step #1: Airway: Profoundly shocked pt’s with severe acidosis or impaired conscious level should be intubated and ventilated within 15 minutes….use rapid sequence intubation with cardio-stable agents such as etomidate or ketamine. Use low tidal volumes and peak inspiratory pressures to prevent the reduction in venous return that is associated with positive pressure ventilation.

Step #2 is Fluid resuscitation if hypovolemia suspected (most forms of shock): NS or LR generously (~2L in adults) but cautiously to raise SBP to 90-100 mmHg. If develops SOB, rales, distended neck veins then overhydration has occurred (consider a PA cath to guide therapy). Aim for a mean arterial pressure of 65mmHg to maintain cerebral perfusion. If the pressure fails to rise after 2L IVF, then start vasopressors. Consider intra-arterial pressure monitoring. If unresponsive to initial fluids and altered MS or UGI bleed, consider ETT and ventilator support. Keep blood glucose <110 mg/dL to reduce M&M (NEJM 2001;345:1359-67).

• Albumin for volume resuscitation and volume expansion in the critically ill is associated with increased mortality (Cochrane Database Syst Rev 2002;CD001208).

• Fluid therapy can be harmful in a pt with AMI, CHF or with an arrhythmia that may progress to cardiogenic shock with LV failure and pulmonary edema…..if unsure, then a fluid challenge (usually 250 ml of crystalloid over two minutes) should be given amd the response to this fluid challenge should be noted and if the pt seems to improve (BP up, HR down, peripheral perfusion improved), then fluid loss should be assumed and further fluid should be given (Critical care in the emergency department: shock and circulatory support. Emerg Med J 2005; 22:17-21).

Signs of an adequate initial response: improving conscious level, warm peripheries, urine output >1 ml/kg/h.

Signs of poor response: pt’s conscious level is deteriorating, hemodynamic parameters worsening, decr BP, an increasing metabolic acidosis. Consider intubation or assessment of filling of the venous circulation by using a central venous pressure monitored fluid challenge.

Hemodynamic monitoring–> Swan-Ganz or bedside parameters such as UO, acid-base status, level of sensorium, skin temp. If on a statin, keep the dose going (even if unconscious) as withdrawal increases event rates of acute coronary syndromes (Circulation 2002;105:1446-52).

Estimated Fluid and Blood Requirements in Shock:

Class I: Blood Loss (ml) @ up to 750 (up to 15% BV). Pulse @ 100. BP Normal. Pulse Pressure is normal or increased. Capillary Blanch Test is normal. RR is 14-20. Urine Output >30 ml/hr. CNS-Mental Status is slightly anxious. Fluid Replacement (3:1 Rule) via Crystalloid.

Class II: Blood Loss (ml) @ 750-1500 (15-30% BV). Pulse @ 110. BP Normal. Pulse Pressure is decreased. Capillary Blanch Test is positive. RR is 20-30. Urine Output 20-30 ml/hr. CNS-Mental Status is mildly anxious. Fluid Replacement (3:1 Rule) via Crystalloid.

Class III: Blood Loss (ml) @ 1500-2000 (30-40% BV).Pulse @ 120. BP Decreased. Pulse Pressure is decreased. Capillary Blanch Test is positive. RR is 30-40. Urine Output 5-15 ml/hr. CNS-Mental Status is anxious & confused. Fluid Replacement (3:1 Rule) via Crystalloid & blood.

Class IV: Blood Loss (ml) @ >2000 (>40% BV). Pulse @ >140. BP Decreased. Pulse Pressure is decreased. Capillary Blanch Test is positive. RR is >40. Urine Output negligible. CNS-Mental Status is confused-lethargic. Fluid Replacement (3:1 Rule) via Crystalloid & blood.

Adequate volume replacement call be guided by urinary Output. 50ml/ hour is a minimum objective of resuscitation for an adult. This figure should be doubled in cases of crush injury.

Vasopressors:

Indications for Inotropic Support: shock with or without hypotension is unresponsive to fluid management. This is seen in cardiogenic shock with predominant left ventricular failure or in severe septic shock after CVP guided fluid boluses are producing no further benefit or are giving rise to significant increases in CVP. Also may be required in the post-cardiac arrest setting and in anaphylactic or neurogenic shock that is resistant to fluid therapy. The goals is to raise cardiac output by increasing the heart rate and stroke volume for a given preload and to exert an appropriate effect on the peripheral vascular system.

Autonomic Nervous System:

Adrenergic Receptors: alpha-1–> constricts the peripheral vascular and coronary smooth muscle.

Beta-1–> acts on myocardium to increase rate and contractility.

Beta-2–> dilates bronchial, peripheral vascular and coronary smooth muscle.

Dopamine–> dilates renal vasculature and GI smooth muscle, shown to decrease mortality.

Dopamine (DA, Intropin): 5-20 mcg/kg/min.

0.5-2 mcg/kg/min = Renal Dose, for oliguria despite “normal” BP as dopaminergic (metaanalysis shows that it is not effective at tx or PV of ARF, Crit Care Med 2001;29:1526).

2-10 mcg/kg/min is Beta-1.

10-20 mcg/kg/min is Alpha-1 (high arrhythmogenic potential).

2-15 for emergency tx of hypotension of any cause.

1-10 for hypotension due to sepsis.

Low dose (0.5 to 3 mcg/kg/min): selectively activates dopamine-specific receptors in the renal, mesenteric, and cerebral circulations and increases blood flow in these regions.

Intermediate dose (3 to 7.5 mcg/kg/min): stimulates b-receptors in the heart and peripheral circulations, and this produces an increase in cardiac output. The inotropic response to dopamine is modest when compared to dobutamine.

High dose (> 7.5 mcg/kg/min): produces a dose-dependent activation of a-receptors in the systemic and pulmonary circulations. This results in progressive vasoconstriction, and the resultant increase in ventricular afterload limits the ability of dopamine to augment cardiac output.

Prep: Add 200 to 400 mg dopamine to 250 mL sodium chloride 0.9% (normal saline, NS) or glucose 5% injection, (Dextrose, D5W), to produce 800 or 1600 mg/mL. Alternatively, add 400 mg to 500 mL of NS or D5W to produce 800 mg/mL.

Dobutamine (Dobutrex): 2-20 mcg/kg/min. For cardiogenic shock, cardiac induced pulmonary edema (CHF), not used alone if pt is hypotensive as only increased CO, not SBP. Beta-1 and Beta-2. Good if hypertensive or normotensive. A large randomized trial shows no difference in death rates with the use of Dopamine vs. Norepinephrine in 1679 adult patients with shcok, but significantly higher mortality with dopamine among patients with cardiogenic shock (NEJM 2010;362:779)……However, significantly more patients in the dopamine group than in the norepinephrine group experienced arrhythmias (24% vs. 12%)…….The authors “strongly challenge” the current American College of Cardiology–American Heart Association guidelines that recommend dopamine as a first-line agent for cardiogenic shock……No evidence supports one agent over the other for different forms of shock.

Norepinephrine (NE, Levophed): 0.5-30 mcg/min IV. For emergency tx of hypotension from any cause, especially sepsis. Alpha-1 & Beta-1. In the volume-replete pt (after volume resuscitation), NE is often the vasopressor of choice. Norepinephrine increases mean arterial pressure in septic shock pt’s and can also improve renal function (Chest 2004;126:335-336,534-539). The mean max dose given to septic shock pt’s is 1.3 micrograms/kg/min, while the dose for head trauma pt’s is 0.3 micrograms/kg/min.

Epinephrine (Levarterenol): 0.5-10 mcg/min for anaphylaxis, pulseless arrest and sepsis. Alpha-1, Beta-1 and Beta-2. High arrhythmogenic potential.

Phenylephrine (Neo-Synephrine): usual dose is 40-180 mcg/min in shock. 0.1-0.5 mg IV, then 0.05-0.2 mg/min for neurogenic shock. Pure alpha-1. Can be used with calcium channel blocker OD.

Isoproterenol (Isuprel): 1-10 mcg/min for bradycardia. Sympathomimetic, Beta-1 and Beta-2. High arrhythmogenic potential.

Indications: Symptomatic bradycardia, refractory torsade de pointes unresponsive to magnesium, bradycardia in heart transplant patients, beta blocker poisoning.

Dose: IV infusion: mix 1 mg/250 mL in normal saline, lactated Ringer’s solution, or D5W, run at 2–10 mcg/min, and titrate to pt response. In torsade de pointes titrate to increase heart rate until VT is suppressed.

Metaraminol (Aramine): 0.5-5 mg IV bolus, then 5-15 mcg/kg/min for neurogenic shock.

Hemodynamic Profiles:

Drug –>\SVR\CO\HR\Inotropy\VO2.

DA- low –>\decr\incr\incr\incr\Incr.

DA- high –>\3+ incr\2+ incr\2+ incr\2+ incr\2+ incr.

Dobutamine –>\decr\2+ incr\2+ incr\2+ incr\3+ incr.

Epi –>\2+ incr\2+ incr\3+ incr\2+ incr\3+ incr.

NE –>\3+ incr\incr\3+ incr\2+ incr\Incr.

Isuprel –>\2+ decr\2+ incr\3+ incr\incr\3+ incr.

Phosphodiesterase Inhibitors:

Amrinone (Inocor): 0.75 mg/kg IV over 3min, then 5-15 mcg/kg/min as short term incr cardiac contractility when catecholamine therapy is hazardous such as arrhythmia or ischemia. Has no adrenergic effects.

Milrinone (Primacor): Adult @ 50 mcg/kg IV bolus over 10 min, followed by a continuous infusion of 0.375–0.75 mcg/kg/min and titrate to effect.

Child @ 50 mcg/kg IV bolus over 15 min, followed by a continuous infusion of 0.5–1 mcg/kg/min and titrate to effect.

Info: Contra in severe aortic stenosis, severe pulmonic stenosis, and acute MI. May cause headache, dysrhythmias, hypotension, hypokalemia, nausea, vomiting, anorexia, abdominal pain, hepatotoxicity, and thrombocytopenia. Pediatric pt’s may require higher mcg/kg/min doses because of a faster elimination T1/2 and larger volume of distribution, when compared with adults. Hemodynamic effects can last up to 3–5 hr after discontinuation of infusion in children. Reduce dose in renal impairment.

Remember that Cardiac Pressors do not Work in a Low-pH Environment:

Critically ill patients often require inotropic and/or pressor support to maintain adequate cardiac output and adequate blood pressure to sustain end-organ perfusion. Because end-organ perfusion has already likely been compromised and may continue to be problematic despite use of these agents, anaerobic metabolism rather than aerobic metabolism is likely to be generating a limited amount adenosine triphosphate (ATP) in the hypoperfused tissues. The consequence is lactic acid production and acidosis. Additionally, critically ill patients may have other causes of acidosis contributing to the overall acidotic state including renal failure, hyperchloremia, or ketoacidosis. The acidosis may be severe with pH values well below 7.0.

Binding of the inotropic or pressor agents to their receptors is influenced by pH, along with other factors such as temperature and concentration. Presumably, the greater the deviation in either direction from the optimal pH for the drug-ligand interaction, the less binding that will occur and hence, the less the effect of the drug. This has led to the widely held opinion that inotropes and vasopressors don’t work at the acidic pH values often encountered in critically ill patients. The actual relationship is much more complex since the target of the inotropes and vasopressors, the alpha and beta adrenergic receptors, includes several subtypes whose individual responsiveness to these agents is quite variable under acidic conditions.

Watch Out For: The variability in responsiveness stems from not only changes in affinity for binding to the receptors but also because acidic conditions have been shown to change receptor numbers on cell surfaces as well as alter the downstream regulation mediated by G-coupled proteins. Some receptors are upregulated while their binding affinity may drop. Others exhibit no change in their affinity or overall responsiveness to inotropes and vasopressors. Still others increase their responsiveness. Different blood vessels in different tissue beds also are highly variable in their responsiveness since the predominant population of the receptor subtype present varies with the site and even caliber of the vessel. The degree of pH change influences these results dramatically. Mild acidemia actually stimulates the sympathetic nervous system output, increasing ventricular function and vasomotor tone. As the acidemia becomes more severe, changes in ligand binding and pharmacological effect of circulating catecholamines may become more prominent. The final clinical effect will be a balance between the two competing phenomena. Overall, pH values as low as 7.15 do not have an appreciable clinical effect on the activity of these drugs. Below this value, however, reductions in overall effectiveness may become clinically apparent.

It is often noted that when bicarbonate is given, blood pressure improves and vasopressors can be titrated. One explanation for this benefit is that an ampule of sodium bicarbonate acts as a hypertonic fluid bolus expanding plasma volume. Additionally, the change in pH alone can have effects on vasomotor tone separate from any effects on drug binding and this may be prominent when a certain pH threshold is crossed. Treatment of an acidotic pH with bicarbonate, with the goal of improving inotrope and vasopressor effectiveness, should be reserved for when the pH is below 7.1. Other reasons for wanting to correct the acidosis when the pH is above this value may exist (such as facilitating weaning from a mechanical ventilator) but significant improvement in the effectiveness of inotropes and vasopressors with bicarbonate administration should not be expected at less acidotic pH values. As always, simply relying on bicarbonate infusion to correct pH should not alter an aggressive search for and treatment of the underlying cause of the acidosis.

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