Shock: Classification, Pathophysiclogical Characteristics, and Management | Chapter 5 Chapter 5 103 Shock: Classification, Pathophysiological Characteristics, and Management Antoinette Spevetz, MD, FCCM, FACP, and Joseph E. Parrillo, MD, FACC, MCCM Key words: shock, hypovolemic shock, cardiogenic shock, extracardiac obstructive shock, distributive shock Disclosures: Dr. Parrllo has had consultancies with NHLBI Heart Failure Network, Sangar, Artisan, Philips, and CytoSorbents. He has received grants from RWJ Fari, New Jersey Health Initiatives, and Salem Health and Wellness. Dr. Spevetz has not disclosed any potential conflicts of interest Shock was first described in 1737 by the French surgeon Le Dran, who used the term in the setting of gunshot ‘wounds to indicate a severe impact or jolt to the body.! twas further refined in 1867 by Morris to describe not only the trauma but the body’s response to the insult. The definition has continued to evolve over the years with further advances in shock research, particularly with the military conflicts in World War I and I and the Korean and Vietnam Wars, Currently. shock is defined as inadequate tissue perfusion resulting in cellular injury. Ultimately, this causes the release of inflammatory mediators that further compromise tissue perfusion, resulting in organ failure and death unless quickly corrected.’ Correction of the underly shock state. Thus, the circulating volume must be identified ng process can reverse the progression of the and expanded quickly,and the underiying pathological process must be controlled. In the shock ive tissue perfusion is decreased secondary to a global reduction in perfusion (i, low cardiac output [CO] states). maldistribution of the blood flow, ora defect in substrate utilization at the subcellular level,104 Chapter | Comprehensive Critical Care: Adult ‘Shock may well be the most common and important problem encountered in the ICU, Cardiogenic shock is one of the critical complications of ischemic heart disease and n the United States is the number one cause of mortal Hypovolemie shock and extracardiac obstructive shock are major contributors to trauma-associated morbidity and mortality. Final hock is the L1th most frequent cause of death in the United States* CLASSIFICATION OF SHOCK Shock can be classified as hypovolemic, cardiogenic, cextracardiac obstructive, distributive, and mixed (Table 1 ‘on page 108). Hypovolemic Shock Hypovolemie shock results from a loss of blood or fluid, Decreased circulating blood volume leads to a decrease in diastole filling pressure and volume, which results in inadequate CO, hypotension, and shock. Cardiogenic Shock Cardiogenic shock is marked by the reduced cardiac function resulting from direct myocardial damage or mechanical abnormality output and blood pressure. ling to a decrease in cardiac Extracardiac Obstructive Shock Extracardiac obstructive shock results secondary to obstruction to flow in the cardiovascular circuit. This leads to inadequate diastole filling or decreased systolic function secondary to an increase in afterload and a drop in CO and blood pressure, Distributive Shock Distributive shock is char Icading 10 a decrease in preload that leads 10 hypotension witha normal or increased eardiae output, Myocardial rized by vasodilatation depression frequently accompanies listributive shock, Typically a deerease in systemic vascular resistance (SVR), an increase in CO, and a decrease in blood pressure are seen. This results from mediator effects at the microvascular level that procluce inadequate blood pressure and cause multiorgan dysfunction. Mixed Shock Mixed shock oecurs when 2 or more processes occur simultaneously. such as when myocardial depression is seen in the face of septic shock. PATHOPHYSIOLOGICAL CHARACTERISTICS OF SHOCK Although there are different causes of shock, most involve similar biochemical and metabolic pathways. In essence, the cardiovascular system is unable to adapt to.an insult, be it sepsis blood loss.or trauma, such that CO and blood pressure are compromised (Figure 1 on page 106). Blood pressure typically depends on the CO and SVR. The brain and heart are able to autoregulate blood flow over a wide range of blood pressures from a mean arterial pressure (MAP) of 50 to 150 mm Hig,as seen in Figure 2 on page 106.’ Hence, a MAP below this range indicates severe reduction in CO, Cardiac output isthe product of heart rate (HR) times stroke volume (SV) (CO = HR x SV). Stroke volume in turn depends on preload, afterload, and contractility. Preload is dependent intrathoracic pressures, Preload is end-diastolic ventricular ating volume, venous time, atrial contraction, and volume. Clinically, we use central venous pressure (CVP) and pulmonary capillary wedge pressure as es id: however, these are not always reliable estimates. iimates of preloa Afterloaa is the resistance to blood flow from the ventricle afterload is equated action, Left ventricula cal properties of the arterial side of the SVR is clinically our best tool with exch com to the mechani circulatory system. The toassessaftertoad. Contractility refers to the intrinsic ibility of the myocardial fibers to shorten under varying, Toads Its assessed via apy looking at pe systolic pressure to end-systolic volume ratio, In the shock state, contractility is depressed from acidosis, myocardial depressant factors. and ischemia, a seen in Figure 3 on page 106,Shock: Classification, Pathophysiological Characteristics, and Management | Chapter 105 Table 1. Classification of Shock Fiypovolemic (Oligemic) Pharmacological Cardiac tarnponade Hemorthagic ‘Anthracydline cardiotoxicity Aa ‘Trauma Calcium channel blockers Post-myocardial infarction Gastrointestinal Mechanical free wall rupture Retroperitoneal Valvular failure (stenotic or Traumatic Fluid depletion (nonhemorthagie) regurgitant) Hemorthagic External fluid loss Hypertrophic cardiomyopathy (anticoagulation) Dehydration Ventricular septal defect Chronic Vomiting Arthytheic Malignant Diarrhea Bredycardia Uremic Polyuria Sinus (eg, vagal syncope) Idiopathic Atrioventricular blocks Impaired systolic contraction Interstitial fluid redistribution (increased ventricular afterload) Thermal injury Tachycardia Right ventricle eure Supraventricular Pulmonary embolus (massive) ‘Anaphylaxis Ventricular ‘Acute pulmonary Increased vascular capacitance Extracardiac Obstructive hypertension (vasodilation) Impaired diastolic filling (ecreased Left ventricle Sepsis ventricular preload) Saddle embolus Anaphylanis Direct venous obstruction (vena Aericchessciion Toxins/drugs cava) a Intrathoracic obstructive Distributive carogenc tumors Septic (bacterial, fungal, viral, Myopathi eee Increased intrathoracic pressure __“ickettsal) Myocardial infarction (decreased transmural Tevic shock androme Left ventricle pressure gradient) Anaphylacti, anaphylactoid Right ventricle Tension pneumothorax Neurogenic (spinal shock) Myocardial contusion (trauma) Mechanical ventilation (with Endocrinological Myocarditis positive end-expiratory Adele hom pressure or volume oer yopathy on depletion) Thyroid storm ischemic myocardi ‘ pars emyocs Decreased cardiac compliance TOXIC (¢g, nitroprusside, bretylium) Septic rjocerdiel dapresskin Constrictive pericarditis Reproduced with permission from Elsevier."106 Chapter 5 | Comprehensive Critical Care: Adult Figure 1. exmnacsnowc oss{aucrvE cAnoiogENG —vPovoLEMG ——_oisTABUTVE (e.g. myocardial (6.9. hemorrhage) (e.g. septic) ven) \orpeas ate tog feensodaataond—yccrcia cxnage myocar Jana son (e.9,tenson preumothorexor (eg: massive pummenary (Geystote and ;eriearial tamponade) ‘ombolus) {sasige ting | syste and diastole turetion 40 mEqiml 2% 350 mOsnv In cithosis and CHF <20 mEq/L <1% Abbreviations: ATN, acute tubular necrosis; CHF, congestive heart failure; Fe, iron; Na, sodium; Una, urine sodium; Uosmo, urine osmolality.112 ChapterS | Comprehensive Critical Cara: Adult be seen, Ischemia of the gut can lead to translocation of bacteria from the gut to the circulation.’* Similarly, the liver may exhibit elevated transaminases and lactate dehydrogenase. The values typically peak in L103 days and then normalize, Hematological Shock can cause disseminated intravascular coagulation (DIC) by activation of the coagulation and fibrinolysis cascades. Sepsis and DIC can be differentiated by ‘measuring a factor VIII level, which is normal or increased in hepatic dysfunction, Unless there is extensive trauma ot bleeding, DIC is not seen with hemorthagie shock. ‘Thrombocytopenia, which i dilutional, s commonly seen following resuscitation.” Metabolic Hyperglycemia is commonly seen in shock seconclary to a deerease in insulin release. Additionally, epinephrine release results in skeletal muscle insulin resistance in order to preserve glucose for the heart and brain. Another ‘common m catabolism, resulting tabolic derangement is increased protein a negative nitrogen balance. Immune System Immune dysfunction likely contributes to late mortality shock. The mucosal barrier of the gut may of bacteria, be disrupted, eading to translocat Inflammation, ischemia, and free radical injury occur, as ‘well as dysfunction of the cellular and humoral immune system, Medications used in resuscitation also can play a role. Dopamine suppresses the pituitary production of prolactin, which suppresses the Teel proliferative response." This immunological dysfunction may account for the ultimate mortality of patients late in their course from ongoing sources of infection, THERAPEUTICS Shock isa life-threatening emergency that must be KR essively. Although, ygnized immediately and treated «carly identification of the cause of the shock is important, studies often cannot be done immediately given the patient's severity of illness and inability to be moved. Patients typically present with hypotension, tachycardia, tachypnea, and oliguria. The extremities are cool and may become mottled, The patient may have an altered mental status There may be clues to differentiate among the causes of shock, such as the following examples: Patients with cardiogenic shock often have jugular , and regurgi venous distension, an S, and murmurs * With pulmonary embolus, patients present with hypoxia, dyspnea, and elevated right heart pressures, + Incardiac tamponade, the patient often has pulsus paradoxus and distant heart tones. ‘+ Septic shock patients may have fevers, chills, and usually q anidus of infection, Laboratory Studies ‘Common findings include the following: + Lowor high white blood cell count with a left shift and bands + High or normal hemoglobin levels (unless hemorthagie shock) ‘+ High to low platelets + Lowserum bicarbonate + High anion ga + High or normal creatinine + High lactate Hemodynamic Monitoring Hemodynamic monitoring should be initiated if the patient does not respond to initial therapy. Ifthe patient requires vasopressors, arterial pressure monitoring is useful. CentralShock: Classification, Pathophysiological Characteristics, and Management | Chapter 5 Venous pressure monitoring may likewise be useful to guide volume resuscitation, understanding that CVP may not reflect the actual intravascular volume in all patients. Table 3 on page 114 depicts hemodynamic parameters seen in the various forms of shock. There is controversy regarding the use of pulmonary artery catheters in shock, most studies documenting no benefit in mortality Some information can be gleaned by waveform analysis such as looking for a step-up in oxygenation and following the response to therapeutic interventions. Mixed venous gen saturation (Svo,) level obtained via either CVP or a pulmonary a useful parameter to follow during resuscitation, As perfusion increases Svo, rises. and vice versa. A normal Sv0, is 65% to 75%. Lactate levels begin to increase when the Svo, falls below 30%. Appropriate resuscitation from shock requires achievement of an adequate CO and MAP. Recent studies, ipport the concept that the speed of implementation may be related to improved outcomes. This is seen in the golden hour in hypovolemie shock with trauma, the early use of antibiotics with septic shock,” and early reperfusion in cardiogenie shock secondary to myocardial infarction, Resuscitation involves frst assessing respiratory status and securing the airway. Oxygenation and ventilation must be censured, Oxygen saturation 0% or greater is the goal Full ventilator support must be given to decrease systemic oxygen demand, Circulatory shock is treated with aggressive volume resuscitation with erystalloids Patients with cardiomyopathy may require higher filling pressures. ‘Those with ARDS and altered vascular permeability may fare better with lower pressures The use of colloid versus crystalloid for resuscitation is controversial. In a large randomized study of albumin versus normal sali resuscitating with albumin did not show a bene! outcome! Subgroup analysis suggests that there may be some benefit to resuscitating patients with albumin in the setting of severe sepsis” Hetastarch isa volume expander, but its use is limited in patients with renal failure and those who might experience dilutional coagulopathy:** Blood product transfusion is a controversial topic. One study 113 showed that a hemoglobin level of 7 g/dL is appropriate for most patients, but anytime one transfuses, the risks and ber 8 ‘of giving blood products must be considered. Once the intravascular Volume is optimized, the next line of therapy includes vasopressors and inotropes. Table 4 ‘on page 116 summarizes the various vasopressors. Typically, the intial vasopressor used for circulatory shock is norepinephrine, a potent vasoconstrictor and inotrope. i appears to provide a more reliable increase in blood pressure than dopamine. However, dopamine can be considered as well. At lower doses dopamine has a mild inotropic effect as well as some renal effects At higher doses dopamine causes vasoconstriction, Dopan can cause tachycardia and arrhythmias and has a higher incidence of mesenteric ischemia than norepinephrine." Epinephrine isthe first line of therapy in anaphylactic shock and is useful to support the patient post cardiopulmonary bypass Epinephrine has both inotropic and vasopressor effects It is associated with mesenteric ischemia. Phenylephrine is a pure c-agonist and is used intraoperatively and in patients who have an underlying tachycardia. Vasopressin has recently been used in septic shock when other vasopressors have failed to normalize blood pressure. Vasopressin decreases cardiac output and heart rate while increasing blood pressure and pulmonary artery pressure, It may increase myocardial ischemia from ‘a decrease in coronary blood flow, which may lead to myocardial infarction. Inotropes such as dobutamine are useful. Dobutamine stimulates both the BI and B2 receptors thus increasing CO while decreasing SVR. Milrinone isa phosphodiesterase inhibitor that induces a positive inotropic state. It is a potent vasodilator that decreases both pulmonary vascular resistance and SVR. CLINICAL APPROACH TO SHOCK ‘The immediate goals in shock are to restore blood pressure and circulating volume, Goals are to achieve a MAP greater than 60 mm Hg, CVP greater than 8 mm Hg, and cardiacindex greater than 22 L/min/m’ in hopes114 ChapterS | Comprehensive Critical Care: Adult Table 3. Hemodynamic Profiles of Shock” Diagnosis co SVR PWP Cardiogenic shock Caused by myocardial dysfunction A. t t Caused by a mechanical defect, Acute ventricular septal defect woo Lt it nlor? RVCO > WO ‘Acute mitral egurgitation Forward CO Lt 1 7 Right ventricular infarction uu t stort Extracardiac obstructive shock Pericardial tamponade Lor t tT Massive pulmonary emboli u t lord Fiypovolemic shock w T Ww Distributive shock Septic shock Mornlrartely! — Lor Lb Lornl Anaphylaxis TMornlrartely) Lord Lorn! Abbreviations: CO, cardiac output; CVP. central venous pressure; LY left ventricular; nl, normal; PWR, pulmonary wedge pressure; Svo,, mixed venous oxygen saturation; SVR, systemic vascular resistance; 1? or 1, mild to moderate increase or decrease; 'T or 1, moderate to severe increase or decrease. ‘The hemodynamic profiles summarized in this table refer to patients with the diagnosis listed in the left column who are also in shock (mean arterial blood pressure <60-65 mm Hg). Reproduced with permission from Elsevier.™#9Shock: Classification, Pathophysiclogical Characteristics, and Management | Chapter 115 CP Sv0, ‘Comments tT Usually occurs with evidence of myocardial infarction (=40% of left ventricular myocardium nonfunctional), severe cardiomyopathy, or myocarditis tT Tortt If shunt is left-to-right, pulmonary blood flow is greater than systemic blood flow; oxygen saturation “step-up"(25%) occurs at right ventricular level; 7 Svo, is caused by left to right shunt Tort 4 Large V waves (210 mm Hg) in pulmonary wedge pressure tracing Tt J Elevated right atrial and right ventricular filimg pressures with low ‘or normal pulmonary wedge pressures tt L Dip and plateau in right and left ventricular pressure tracings. The right atrial mean, right ventricular end-diastolic, pulmonary artery ‘end-diastolic, and pulmonary wedge pressures are within 5 mm Hg of each other at 4 Usual finding is elevated right-sided! heart pressures with low or normal pulmonary wedge pressure Ww T Filling pressures may appear normal if hypovolemia occurs in the setting of baseline myocardial compromise Lornl Tortt “The hyperdynamic circulatorey state (TCO, . SVR) associated with distributive forms of shock usvally depends on resuscitation with fluids; before such resuscitation, a hypodynamic circulation is typical Lornt Forth116 Chapter S | Comprehensive Critical Care: Adult Table 4. Relative Potency of Intravenously Administered Vasopressors/Inotropes Used in Shock* Cardiac Dose Heart Rate Contractility j Dopamine Ta ugikgimin 1+ 1-24 5-10 j1g/kg/min 2s 2 11-20 pig/kg/min 2b 24 Norepinephrine 2-20 tig/min 2 2 Dobutamine 1-20 ig/kg/min 1-2 3+ Dopexamine™ 05-6 ygikg/min a ro Epinephrine 1-8 uigimin ae oF Phenylephrine 20-200 nig/min oO ro Isoproterenol 1-8 g/min a a Vassopressin 004-0.12 ymin (tart 002-0047 0 0 min; fitrate up 0.02-0.04 y/min q every 20-30 Milrinone 37-5-15 g/kg bolus over 10min; 1+ 3+ 0.375-0.75 wa/ke/ min infusion Abbreviation: CHF, congestive heart failure. "The 1-4+ scoring system represents an arbitrary quantitation of the comparative potency of vasopressors/inotropes. *Not clinically released in the United States. Reproduced with permission from Elsevier.**" of maintain 1g oxygen delivery and preventing organ dysfunction, Hypovolemie shock is hy sleerease in preload resulting in decreased tilling pressures and a terized by decrease in blood pressure. Hypovolemic shock ean be caused by dehydration, hemorrhage, gastrointestinal uid loses urinary losses, or decreased vascular permeability {rom sepsis Patients have tachycardia, hypotension, decreased filling pressures, low i ine output, altered mental status and cool, clammy, motte skin, The severity of nount and the hypovolemic shock depends on both the. severity of the fluid loss Acute loss of 10% of circulating blood volume results in tachycardia and an inerease in SVR, but blood pressure is maintained. A loss of 20% to 25% results in mild hypotension, Cardiae output starts to decrease and lnetate production begins With a loss of 40% shock indicating tissue hypoperfusion, activation of the e with signs of othe pati t becomes hypotensi inflammatory cascade, and widespread cellular damage. Rapid reversal of this process with blood, colloid, or crystalloid is require.Shock: Classification, Pathophysiological Characteristics, and Management | ChapterS 117 Peripheral Vasculature Vasoconstriction Vasodiltation Dopaminergic ‘Typical Clinical Use 0 + a All shock 1-24 1+ ae 234 1+ 4+ a oO 0 Refractory shock 1 2 0 CHF; cardiogenic, obstructive and septic shock 0 sae a CHE; cardiogenic shock a 3 0 Refractory shock or anaphylactic shock a 0 0 Neurogenic or septic shock 0 ae 0 Cardiogenic shock (braciyarrhythmia), torsade de pointes, ventricular tachycardia a 0 0 Vasodilatary (e.g. septio) shock 0 a 0 CHF; cardiogenic shock Cardiogenie shock is caused by failure of the heart as a pump. Cardiogenie shock can be caused by myocardial valvular or structural abnormalities Its the most common, cause of in-hospital mortality in patients with Q-wave ‘myocardial infarctions. There is increased ventricular preload with increases in pulmonary capillary wedge pressure and CVP as well as ventricular volume, This results in a decrease in cardiac index, SV,and MAP result of the failing pump. Patients heart failure, an S,.elevated neck veins, and peripheral a ce signs of congestive hypoperfusion, Mortality is improved for cardiogenic shock caused by surgically correctable lesions In the setting of left ventricular infarct, itraaortic balloon pump, cardiac angiography ‘management, With right-sided infarcts, ids and inotropes are the mainstay of therapy, and pulmonary artery catheter monitoring may be helpful to guide therapy. For valvular ‘or mechanical abnormalities, echocardiogram, cardiac catheterization, and surgery may be warranted. ind revascularization are options for Extracardiac obstructive shock results from obstruction to flow in the cardiovascular circuit, Causes include118 Chapter S | Comprehensive Critical Cara: Adult cardiac tamponade, constrictive pericarditis, and pulmonary embolus Cardiac tamponade and constrictive Pericarditis impair diastolic filling of the right ventricle, Hemodynamically, increased and equalized right and Jeft ventricular diastolic pressures usually develop. Acute pulmonary embolus results in right heart failure with clevated pulmonary artery and right heart pressure with Jow or normal left hear filling pressures. Other causes ‘of obstructive shock include tension pneumothorax and ‘mediastinal tumors As with other types of shock, the acuity of the shock affects the body's ability to compensate. An acute accumulation of as little as 150 mL of blood in the myocardium can result in immediate tamponade and shock: conversely the slow aecumulation of 1 to2 L of {uid can occur before the patient shows signs of shock. Management involves a quick diagnosis, which often can be made with echocardiogram. If cardiac tampo is diagnosed, pericardiocentesis or surgical drainage is ceded. In the case of a pulmonary embolus diagnos (usually made by chest computed tomography) heparin is initiated, and in the case of profound shock and hypoxia, thrombolytic therapy or an embolectomy should be considered. Distributive shock is defined by a loss of peripheral resistance, septic shoek being the leading example. Other examples include anaphylaxis drug overdose, neurogenic causes, and Addisonian crisis. There is an overall decrease in SVR and fluid leak from the microvasculature, leading to inadequate intravascular volume and decreased preload, Yo Characte sVand Additionally myocardial depression is seen, whi ime resuscitation improves the preload. tically, a normal or elevated CO, normal tachycardia are seen as well as hypotension, characterized by decreased stroke work in response 10 volume loading, biventricular reduction in ejection fraction, and ventricular dilatation. This is an attempt to compensate for the depressed ejection fraction and to maintain SV, Treatment involves identification of the source of infection if possible and drainage or removal of a foreign body if possible. Appropriate antibiotic therapy, uid resuscitation, and vasopressors or inotropes should be initiated as needed to optimize blood pressure and CO, Most patients with severe sepsis will require ventilator support for respiratory failure This should be initiated early Anaphylactic shock is a type of distributive shock caused by release of mediators from mast cells and basophils. sani 1m mediated by the nmediate hypersensit interaction of the antibodies on the surface of the mast cell and basophil with the appropriate antigen. Itcan be triggered by insect envenomations drugs (particularly antibiotics), and, less frequently, heterologous serum, blood transfusions, immunoglobulin, and egg-based icine Anaphylactoid reactions result from direct ‘nonimmunological release of mediators from mast cells and basophils and can also lead to shock. These reactions can be caused by ionic contrast media, opiates, protamine, dextran and hydroxyethyl starch, muscle relaxants and anesthetics. Hemodynamic features of anaphylactic shock re similar to those of septic shock. In addition to these findings, urticaria, angioedema, laryngeal and severe bronchospasm can oceur. Treatment 's of stopping or removing the offending agent ‘and administering steroids, diphenhydramine, H, and H, blockers, and epinephrine for hemodynamic instabil Neurogenie shock involves loss of peripheral vasomotor control secondary to injury or dysfunction of the nervous system. Examples include shock associated with spinal injury, vasovagal syncope, and spinal anesthesia. These are usually sel repletion and vasopressor suppor. mited and transient. Therapy includes volume Adrenal crisis is uncommon and difficult to differentiate from other types of shock, Its life-threatening and requires prompt diagnosis and management, In the ing, it can arise from bilat critical care set adrenal hemorrhage in conjunction with overwhelming is like meningococcal infections or HIV, Adrenal crisis also can be seen with anticoagulation, fungal infections, and malignancy. In the ICU it is not uncommon to see aan inadequate adrenal response leading to hypot ted with steroids and fluid Adrenal crisis is tr resuscitation as needed.Shock: Classification, Pathophysiological Characteristics, and Management | Chapter 119 SUMMARY + Shock: Clinical syndrome resulting from a reduction in tissue perfusion that leads to cellular injury from the inadequate delivery of oxygen and substrate to the tissue, which causes the release of inflammatory ‘mediators that further compromise perfusion of the tissues * Hypovolemic shock: Shock resulting from a loss of blood or uid. Decreased circulating blood volun leads to a decrease in diastole filing pressure and volume, which results in inadequate CO, hypotension, and shock, * Cardiogenic shock: Reduced cardiac function resulting from direct myocardial damage or mechanical abnormality leading to a decrease in cardiac output and blood pressure. * Extracardiae obstructive shock: Obstruetion to flow in the cardiovascular circuit leading to inadequate diastolic filling or decreased systolic function secondary to an increase in afterload and decrease in cardiac output and blood pressure. ‘+ Distributive shock: Shock characterized by vasodilatation leading to a decrease in preload that Jeads to hypotension with a normal or increased cardiae output. REFERENCES 1 Le Dran HE A Treatise, or Reflections Drawn From Practice on Gun-Shot Wounds London: Clarke J, trans; 1743. 2. Morris EA.A Practical Treatise on Shock Afier Operations and injuries. London, UK:.LB. Lippincott & Cos 1867 Parrillo JE. Approach to the patient with shock. In: Goldman L, Ausiello D,eds Cecil Textbook of Medicine. 2314 ed, Philadelphia, PA: Saunders- Elsevier: 2008:742-750, Parrillo JE, Parker MM, Natanson C,et al. Septic shock in humans: advances in the understanding of pathogenesis, cardiovascular dysfunction, and therapy. Ann Intern Med. 190113.22 Kumar A, Partillo JE, Shoe pathophysiology, and approach to management. In: Parrillo JE, Dellinger RP, eds Critical Care Medicine: Principles of Diagnosis and Management in the Adult. 3rd ed. Philadelphia, PA: Mosby: 2008:377-422. lasification, Guyton AC. Textbook of Medical Physiology. 8th ed. Philadelphia, PA: Saunders; 1991 Bond RE Peripheral macro-and microcirculation, In: Schlag G, Redl H, eds. Pathophysiology of Shook, Sepsis and Organ Faiture. Berlin, Germany: Spring ‘Verlag; 1993:893-907 Gutteriez G, Brown SD. Response of the ‘macrocirculation, In: Schlag R, Redl H, eds, Pathophysiology of Shock, Sepsis and Organ Failure. Berlin, Germany: Springer-Verlag; 1993:215-229. ‘Wang P, Hauptman JG, Chaudry LH, Hemorr! produces depression in microvascular blood flow hich persists despite fluid resuscitation, Cire Shock 1990;32307318. |. Harper AM. Autoregulation of cerebral blood flow: influence of the arterial blood pressure on the blood, flow though the cerebral cortex. J Neurol Neurosurg, Psychiatry. 196629398403, |. Purrillo JE, Burch C, Shelhamer JH, etal. circulating myocardial depressant substance in humans with septic shock: septic shock patients with a reduced jection fraction have a circulating factor that sin vitro myocardial cell performance.120 12, 13. 15, n vv. 20, Chapter 5 | Comprehensive Critical Care: Adult Hallstrom S, Vogl C, Red H.et al, Net inotropic plasma activity in canine hypovolemic traumatic, shock: low molecular weight plasma fraction after prolonged hypotension depresses cardiae muscle tro. Cire Shock. 1990;30:129-14, performance in- Hou SH, Bushinsky DA. Wish JB, tal. Hospital acquired renal insulficiency: a prospective study Am J Med, 1983:74243-248, Mainous MR, Deitch BA. Bacterial translocation, In: Schlag G, Redl H, eds Pathophysiology of Shock, Sepsis and Organ Failure. Berlin, Germany: Springer- Verlag 1993:265.278. a, Hemostasis nis. Ann Surg. Counts HB, Haisch C, Simon TL, et in massively transfused trauma pat 1979;190:91-99, Devins SS, Miller A, Herndon BL,et al. Th of dopamine on T serum prolactin in critically ill p 1992:20:164-1649. fects Il proliferative response and dents. Crit Care Med. Connors AF Jr, SperoffT, Dawson NV, et al, The effectiveness of right heart catheterization in the initial care of critically ill patients JA. MA. 1996:276:889-897 Rhodes A, Cusack RU. Newman Pletal. A randomised, controlled tral of the pulmonary artery catheter in critically il paionts fatensive Cure Med. 2002:28:256-264, Sandham JD, Hull RD, Brant RE. controlled trial of the use of pulmonary-artery catheters in high-risk surgieal patients [eomment} N Engl J Med. 20032348514 al. A randomized, Kumar A, Zarychanski RL combi Jn Bet al. Barly y yields improved ration antibiotic th ival compared with monotherapy in septic shock: propensity-matched analysis, Crit Cure Med. 201038:1773-1785, 25, . Patel GP. Grahe JS. Sperry \ .. Parrillo JE, Di |. The SAFE Study Investigators A comparison of albumin and saline for Quid resuscitation in the intensive care unit, NW Engl J Med. 2004;350:2247-2256, ‘The SAFE Study Investigators. Impact of albumin compared to saline on organ function and mortality of patients with severe sepsis [published online ahead of print October 62010). Intensive Care Med, 2011:37:86-96, 23. Green RS, Zed PJ, Melntyre L. Pentastareh resuscitation in severe sepsis and septic shock. CJEM Journal Club, 2010%12:58-61. Vincent JL, Baron JF, Reinhart Ket al, Anemia and blood transfusion in critically ill patients JAMA 2002;288:1499-1507 Corwin HL, Gettinger A, Pearl RG, et al. The CRIT Study: anemia and blood transfusion in the critically i the United States. Crit current clinical practice Care Med. 2004:32:3 al. Efficacy and safety of dopamine versus norepinephrine in the ‘management of septie shock. Shock. 2010;33:375-380. DeBacker D, Biston P, Devriendt J.et al. Comparison oof dopamine and norepinephrine in the treatment of shock. N EnglJ Med. 2010,362:779-789, RP.eds Critical Care Medicine: Principles of Diagnosis and Management in the Adult 3rd ed. Philadelphia, PA: Mosby; 2008,