357CHAPTER 34 Shock States manifest high cardiac output shock 60 Furthermore, they noted that low Scvo2 occurred in children with a low cardiac index (CI), but they also found that children with a hig[.]
CHAPTER 34 Shock States manifest high cardiac output shock.60 Furthermore, they noted that low Scvo2 occurred in children with a low cardiac index (CI), but they also found that children with a high CI could have a low Scvo2.60 Similar findings of low Scvo2 in shock have been reported by other investigators.61,62 It is important to emphasize that the clinical context should always be considered when Scvo2 measurements are interpreted—patients in extreme vasodilatory shock or following mitochondrial poisoning demonstrate elevated Scvo2 (.70%), as the oxygen extraction is severely impaired owing to mitochondrial dysfunction.63,64 Despite an adequate hemodynamic status as quantified by Scvo2, microcirculatory splanchnic hypoperfusion may be present in patients with shock, resulting in significant morbidity and mortality.65 The cause of microcirculatory failure is multifactorial and includes physiologic shunting, maldistributed flow, increased microvascular permeability, and microvascular thrombosis.65 Thus, an increased understanding of microcirculatory aberrations and cellular hypoxia has stimulated a search for a minimally invasive means of sampling regional circulations.66–68 Gastric tonometry,69,70 near-infrared spectroscopy,71,72 rectal tonometry,73 sublingual capnometry,74,75 muscle oxygenation,76 tissue microdialysis,77,78 and orthogonal polarization spectral imaging79,80 are investigational methods to evaluate regional circulation, but their clinical utility remains unproven at this time Repeated evaluations and monitoring of the patient in shock by a competent clinician, with appropriate, timely interventions, remains the most effective and sensitive physiologic monitor available Contemporary Cardiac Output Monitoring in Pediatric Shock The American College of Critical Care Medicine Clinical Practice Parameters for Hemodynamic Support of Pediatric and Neonatal Septic Shock recommend titration of therapy to a cardiac output goal of 3.3 to 6.0 L/min per square meter in patients with persistent catecholamine-resistant shock.58 Historically, pulmonary catheter-directed treatment was considered the gold standard for assessing cardiac function and optimizing oxygen delivery in the hemodynamically unstable patient.81 However, the use of the pulmonary catheter has significantly decreased as trials noted the lack of benefit with the use of pulmonary artery catheters in adult patients admitted to the ICU.82,83 For example, in the Study to Understand Prognoses and Preferences for Outcomes and Risks of Treatments (SUPPORT) trial, the use of right heart catheterization in more than 5700 patients was associated with increased mortality and increased utilization of resources.82 Similarly, a meta-analysis also noted a lack of benefit with the use of pulmonary artery catheters in critically ill patients.84 With the decrease in the use of the pulmonary artery catheter, the search continues for noninvasive cardiac output monitoring devices The ideal attributes of such a device would be that it is reliable, noninvasive, cost-effective, and provides continuous cardiac output monitoring In addition to CI, other variables that help titrate therapy include stroke volume index, indexed systemic vascular resistance, Cao2, and Do2 Several noninvasive CO monitoring devices are available; a review of the various technology platforms that support these devices is beyond the scope of this chapter A detailed review of noninvasive hemodynamic monitoring in the ICU can be found elsewhere in the literature.85,86 357 Treatment General Principles Early identification and aggressive, timely treatment improves the outcome in pediatric shock.87,88 The American Heart Association’s Pediatric Advanced Life Support Guidelines provide a systematic approach to assess shock, focusing the primary goal of management on optimizing and balancing oxygen delivery with oxygen consumption.58 The initial approach for stabilization in a patient with undifferentiated shock is highlighted in Box 34.4 Treatment begins with an assessment of the patient’s airway and breathing to provide adequate oxygen delivery during resuscitation Ensuring sufficient cardiac output through assessment of circulation and end-organ perfusion is imperative, allowing for titration of fluid resuscitation and vasoactive administration During the first hour of resuscitation, attention must be directed to the underlying etiology of the shock state.58 Efforts to reduce oxygen requirements when oxygen delivery is compromised are essential Even routine nursing procedures can increase oxygen consumption by up to 20% to 30% in healthy adults.89 Management should be guided by both the clinical examination and monitoring techniques discussed previously in this chapter and titrated to the desired effect Intubation and Mechanical Ventilation Intubation and mechanical ventilation may be necessary in shock states for several reasons: overt respiratory failure, lack of airway protection, and control of energy expenditure These interventions may reduce oxygen consumption by minimizing respiratory work in addition to improving oxygen delivery.90 Use of sedation and neuromuscular blockade further helps to reduce oxygen consumption related to increased metabolic demand from respiratory work.91 However, clinicians must remain acutely aware of the cardiopulmonary interactions that occur during this intervention to • BOX 34.4 Systematic Approach for Initial Management of Undifferentiated Shock Airway and Breathing Supplemental oxygen Assess need for endotracheal intubation: airway compromise, respiratory failure Circulation Fluid resuscitation Vasoactive infusions Other Identify specific treatments for underlying etiologies • Hemorrhagic shock: blood transfusion • Cardiogenic shock: limit fluids, vasoactive support, mechanical support if needed • Obstructive shock • Tension pneumothorax: needle decompression • Cardiac tamponade: pericardiocentesis • Pulmonary embolism: thrombolytics, surgical intervention • Ductal-dependent lesion: prostaglandin infusion • Anaphylactic shock: epinephrine • Septic shock: antimicrobials Evaluate for electrolyte disturbances 358 S E C T I O N I V Pediatric Critical Care: Cardiovascular understand the impact on cardiac output (see Chapter 32 for further information) Mechanical ventilation can substantially improve oxygen delivery to vital organs, and suboptimal patient-ventilator interactions may result in increased oxygen consumption.90,92 Positive-pressure ventilation decreases preload and increases afterload on the right ventricle The reduction of preload can often be overcome by treating the patient with a rapid fluid bolus prior to or during intubation Positive-pressure ventilation also reduces afterload to the left ventricle, which may improve stroke volume Fluid Resuscitation Regardless of the underlying insult, most patients in shock are hypovolemic, causing a decrease in preload and subsequent decrement of stroke volume and cardiac output Early fluid resuscitation is the cornerstone of therapy.58 Based on the Frank-Starling curve, fluid administration will improve ventricular preload and thus increase ventricular stroke volume Studies of septic pediatric and adult patients showed that early fluid resuscitation was associated with improved patient outcomes; these principles are incorporated in current treatment guidelines.93–95 However, excessive fluid resuscitation in patients with cardiogenic shock and some forms of obstructive shock (massive pulmonary embolism or severe pulmonary hypertension) may rapidly push the patient over the FrankStarling curve into CHF There is considerable debate about the type of fluid therapy that should be administered during acute resuscitation The use of colloids in place of crystalloids to increase oncotic pressure and restore intravascular volume has been studied for the management of different shock states, including severe sepsis and postcardiac surgery.96–98 Studies in severe sepsis have shown that the use of albumin replacements either in conjunction with or in place of crystalloids does not improve survival.96,97 In a retrospective pediatric cohort following cardiac surgery, the use of 5% albumin for resuscitation resulted in fluid overload without appreciable clinical benefit.98 The use of normal saline for resuscitation may result in hyperchloremia and metabolic acidosis, both of which have been associated with worse outcomes and mortality in both children and adults with septic shock.99–104 However, a randomized control trial in critically ill adults showed that resuscitation with balanced crystalloids was associated with lower rates of death, persistent renal dysfunction, and need for renal replacement therapy.105 In a retrospective review of pediatric septic patients, there was no difference in outcomes of mortality, acute kidney injury, or need for renal replacement therapy between balanced solutions and normal saline.106 Due to lack of published clinical experience, it remains to be determined whether the use of balanced crystalloids is associated with significant improvements in outcome in critically ill children Massive transfusion in pediatrics has been defined as a transfusion of 40 mL/kg of any blood product given at any time in the first 24 hours.107 Massive transfusion protocol has been adopted by most pediatric trauma centers to correct hemorrhagic shock with a balanced transfusion ratio of plasma, platelets, and packed red blood cells (PRBCs) The use of such protocols makes physiologic sense and is supported by adult data that demonstrate improved patient outcomes and better hemostasis.108,109 Similar studies in children have not shown the perceived benefit of a balanced transfusion approach in pediatric trauma victims.110–113 For example, in a retrospective review of 6675 pediatric trauma patients in which 105 were massively transfused (.50% of total blood volume in 24 hours), higher plasma/PRBC and platelet/ PRBC ratios were not associated with increased survival.111 Similarly, in a retrospective review of 435 patients in Canada, an occurrence of massive transfusion was noted in only 3% of patients, which was associated with coagulopathy and poor outcomes.113 Thus, further research needs to be conducted to identify optimal ratios of blood product transfusion that would lead to an improved outcome in children Careful attention must be paid to the physiologic responses to fluid resuscitation by the clinician to prevent fluid overload Evidence associating positive fluid balance with increased mortality in critically ill adult and pediatric patients114–117 suggests a need for better predictors of fluid responsiveness and end points of fluid resuscitation.118,119 When sufficient preload has been achieved through fluid resuscitation but the patient remains in shock, other supportive therapies are indicated Vasoactive Infusions Infusions to increase cardiac output and improve peripheral vascular tone are indicated when patients have been adequately fluid-resuscitated but hemodynamics remain unstable Infusions of catecholamines (dopamine, dobutamine, epinephrine, norepinephrine), phosphodiesterase inhibitors (milrinone), and vasopressin are most commonly used The choice of vasoactive infusion is dependent on the physiologic derangement (see Table 34.1) Catecholamines work through stimulation of a1-, a2-, b1-, b2-, and dopaminergic receptors to increase intracellular cyclic guanosine monophosphate (cGMP; Table 34.2) Phosphodiesterase inhibitors increase cGMP by preventing its degradation within the cell (see Chapter 31) Vasopressin causes vasoconstriction by direct stimulation of vascular smooth muscle cell V1-receptors Vasopressin also potentiates systemic adrenergic effects Vasopressin and terlipressin (a synthetic analog of vasopressin with a similar pharmacodynamic profile but with a significantly longer half-life) have also shown some utility in the treatment of catecholamine-resistant shock.120–122 Fenoldopam, a dopamine-receptor agonist, has been used to augment diuresis and improve hemodynamics after cardiac surgery and in septic shock.123,124 Assessment of the patient’s clinical presentation is imperative for the appropriate vasoactive choice Therapies should be tailored to the unique patient situation, and patients should be closely monitored for expected therapeutic response Limited data exist regarding the superiority of these different medications However, there has been recent pediatric data that has shown epinephrine as being more effective and associated with increased survival when compared with dopamine in treatment of septic shock.125,126 Similarly, data from critically ill septic adults suggest the use of norepinephrine over dopamine for firstline treatment of septic shock due to improvement in mortality and lower risk of adverse events.127,128 In adults, nonadrenergic vasopressors, such as vasopressin, have been shown to decrease the amount of catecholamine requirements and reduce mortality when compared with norepinephrine in states of vasodilatory shock.129,130 In addition, clinicians should consider how the use of these vasoactive medications may impact the patient’s physiology and other elements of management For example, epinephrine has been shown to increase serum lactate levels secondary to b2 stimulation.131 Norepinephrine and epinephrine have also been shown to decrease regional blood flow to organs such as the gastrointestinal CHAPTER 34 Shock States 359 TABLE Vasoactive Medications and Mechanism by Receptor Target 34.2 RECEPTOR Vasoactive a1 b1 b2 D1 Dopamine Vasoconstriction Inotropy, chronotropy Vasodilation Renal vasodilation Norepinephrine Vasoconstriction Inotropy Epinephrineb Vasoconstriction Inotropy, chronotropy Vasodilation Inotropy Vasodilation a Dobutamine Vasopressin Potentiates Potentiates Fenoldopam Inamrinone, milrinone V1 Vasoconstriction Renal vasodilation Non–receptor-mediated inotropy, lusitropy, and vasodilation a Dose related: At low infusion rates, D1-receptor effects predominate; at intermediate rates, b1- and b2-receptor effects predominate; at high rates, a1-receptor effects predominate on peripheral vasculature b Dose related: At low infusion rates, b-receptor effects predominate; at high rates, a-receptor effects predominate on peripheral vasculature tract.132,133 Renal clearance of milrinone may limit its utility in patients with significant renal injury or failure Age-Related Therapy Concerns The transition of fetal to neonatal physiology offers a distinct challenge for physicians treating neonatal sepsis The presentation of septic shock in children is different compared with adult patients, presenting the bedside clinician with a diagnostic and therapeutic challenge.134 The differential for neonates presenting with shock in the first month of life must include undiagnosed congenital heart disease with a ductal-dependent lesion In addition to the shock treatment listed earlier, prostaglandin E1 (PGE1) should be initiated immediately when there is any concern for a potential ductal-dependent systemic lesion.58 PGE1 dosing is 0.05 to 0.10 mg/kg per minute, adjusted until adequate systemic perfusion is obtained An echocardiogram should be obtained to confirm diagnosis and determine further surgical intervention needs Shock in infants is frequently complicated by pulmonary hypertension Goals for treatment include the primary principles of shock treatment: maintenance of normothermia, optimization of electrolytes and glucose, and ensuring adequate intravascular volume Vasoactive medications should be used to support cardiac output Mechanical ventilation goals focus on maintaining oxygenation and optimizing lung volumes to maintain functional residual volume and limit pulmonary vascular resistance Some infants may benefit from high-frequency ventilation The addition of pulmonary vasodilators such as inhaled nitric oxide and/ or sildenafil may be of benefit If medical management fails, cannulation to extracorporeal membrane oxygenation support may be required.135 Neonates may experience transient hypocalcemia in the first few days to weeks of life for a variety of reasons.136 In the setting of shock, neonates are at increased risk for hypocalcemia and myocardial dysfunction Neonatal myocardium differs from older children and adults, as it has fewer contractile elements and requires higher extracellular calcium concentrations for contractility.137–139 The finding of hypocalcemia in infants who present in shock should raise the suspicion of left ventricular dysfunction, which is reversible with calcium replacement If hypocalcemia persists following resolution of shock in a neonate, further evaluation for etiology of hypocalcemia is warranted Due to low glycogen stores, infants and very young children may quickly develop hypoglycemia during periods of shock due to increased metabolic requirements Thus, close monitoring of blood glucose levels and appropriate supplementation to maintain euglycemia is imperative.58 In addition, infants and older children with metabolic and mitochondrial disorders may also be highly sensitive to reductions in energy substrates The goals of therapy in these disease states during periods of stress are to provide enough substrate to prevent catabolism, to ensure adequate hydration, and to correct metabolic derangements This may include the use of total parenteral nutrition, intravenous lipids, and concurrent use of insulin therapy with high dextrose delivery.140 Specific Shock State Therapy Considerations Hypovolemic Shock Once the airway is ensured or established, measures to restore an effective circulating blood volume should begin immediately Placement of an adequate intravenous or intraosseous catheter and rapid volume replacement are the most important therapeutic maneuvers to reestablish the circulation in hypovolemic shock The choice of fluid depends on the nature of the loss Hemorrhagic shock should be treated with transfusions of blood components, including emergency transfusion of uncrossmatched blood.141,142 Hematocrit is a poor early indicator of the severity of hemorrhage Depending on the source, surgical intervention may be indicated to control the source of bleeding.143 If the etiology for hypovolemic shock involves ongoing fluid losses from chest tubes, biliary drains, bowel, capillary leak, or other bodily fluids, then resuscitation should be with isotonic or balanced crystalloid solutions 360 S E C T I O N I V Pediatric Critical Care: Cardiovascular Uncomplicated, promptly treated hypovolemic shock usually does not lead to a significant capillary injury and leak However, severe, prolonged hypovolemic shock, traumatic shock with extensive soft-tissue injury, burn shock, or hypovolemic shock complicated by sepsis may seriously impair capillary integrity Therefore, once adequate hemodynamics have been restored, fluid administration should be reduced unless there are ongoing fluid losses Continued assessment of hemodynamic status and vascular volume is essential to guide further therapy If the patient does not show improvement after several fluid boluses, more monitoring and reevaluation of the diagnosis may be required Causes of ongoing vascular depletion and other causes of refractory shock should be determined, including unrecognized pneumothorax or pericardial effusion, intestinal ischemia (volvulus, intussusception, necrotizing enterocolitis), sepsis, myocardial dysfunction, adrenocortical insufficiency, and pulmonary hypertension Arterial blood gases, hematocrit, serum electrolytes, glucose, and calcium should be reevaluated Correction of acidosis, hypoxemia, or metabolic derangements is essential Aerobic and anaerobic cultures should be obtained from blood and other appropriate sites and broad-spectrum parenteral antibiotic coverage should be started if sepsis is suspected Cardiogenic Shock The general supportive and pharmacologic measures used in the treatment of severe congestive heart failure or cardiogenic shock are listed in Box 34.5 The initial therapy for cardiogenic shock is supplemental oxygen and mechanical ventilation to reduce myocardial demand Preload should be optimized to allow the patient to take advantage of Starling mechanisms Correction of metabolic derangements (e.g., pH, glucose, calcium, magnesium) may • BOX 34.5 General Principles in Management of Cardiogenic Shock or Severe Congestive Heart Failure Minimize Myocardial Oxygenation Demands • • • • Intubate and use mechanical ventilation Maintain normal core temperature Provide sedation Improve oxygen-carrying capacity by correcting anemia Maximize Myocardial Performance • • • • Correct dysrhythmias Administer prostaglandins if ductal-dependent lesion is suspected Optimize preload: fluid bolusesa Improve contractility: provide oxygen, mechanical ventilation, correct acidosis and other metabolic abnormalities, inotropic and lusitropic drugs • Reduce afterload: provide sedation and pain relief, correct hypothermia, positive pressure ventilation for left ventricular afterload reduction, appropriate use of vasodilators Mechanical Circulatory Support • Extracorporeal membrane oxygenation • Ventricular assist devices Heart Transplantation a However, if evidence of congestive heart failure on clinical exam, appropriate salt and water restriction as well as appropriate use of venodilators and/or diuretics are indicated enhance cardiac function, and pharmacologic interventions are usually necessary to improve cardiac function (see Tables 34.1 and 34.2) In addition to inotropic effects, catecholamines also possess chronotropic properties and have complex effects on vascular beds of the various organs of the body Consequently, the choice of an agent depends both on the desired myocardial and peripheral vascular effects Vasodilators should be considered in shock states in which cardiac dysfunction is associated with elevated ventricular filling pressures, elevated systemic vascular resistance, and normal or near-normal systemic arterial blood pressure Occasionally, the combination of vasodilator and inotropic therapy results in hemodynamic improvement not attainable with either approach alone Vasodilators improve cardiac performance and lessen clinical symptoms via arterial and venous smooth muscle relaxation Arterial relaxation should increase ejection fraction, increase stroke volume, and decrease end-systolic left ventricular volume Some evidence suggests that vasodilator drugs increase left ventricular compliance, which should improve diastolic function.4 Venous relaxation should shift blood into the periphery and reduce right and left ventricular diastolic volume, having beneficial effects on both pulmonary and systemic capillary pressure This should be reflected in decreased edema, reduced myocardial wall stress, and improved diastolic perfusion of the myocardium Intravenous vasodilators with rapid onsets of action and short half-lives are preferred for treatment of cardiogenic shock Selection of a vasodilator agent would depend on its principal hemodynamic effects and the patient’s specific hemodynamic abnormalities Factors that increase systemic vascular resistance—such as hypothermia, acidosis, hypoxia, pain, and anxiety—should be treated before vasodilator drugs are considered Inamrinone, milrinone, and enoximone belong to a class of nonglycoside, nonsympathomimetic inotropic agents that act via potent and selective inhibition of phosphodiesterase.144 Inamrinone and milrinone are particularly useful in the treatment of cardiogenic shock because they improve diastolic function (lusitropy), increase contractility, and reduce afterload by peripheral vasodilation without a consistent increase in heart rate or myocardial oxygen consumption Both drugs have relatively long half-lives; they should be used cautiously in the presence of hypovolemia and/or hypotension Milrinone is preferred over inamrinone because of inamrinone’s tendency to cause thrombocytopenia The use of milrinone has been shown to be effective in decreasing the risk of low cardiac output syndrome in postoperative cardiac patients.145 Afterload reduction of the failing right ventricle is also an important management concern in cardiopulmonary disorders associated with right heart strain and/or failure, including congenital heart disease, acute respiratory distress syndrome, bronchopulmonary dysplasia, and other chronic pulmonary disorders The ability of the right ventricle to respond to the increased pulmonary vascular resistance seen in these situations often determines outcome Therefore, measures to decrease pulmonary vascular resistance have become more common in the treatment of many seriously ill pediatric patients, including supplemental oxygen, hyperventilation, metabolic and respiratory alkalosis, inhaled nitric oxide, PGE1, prostacyclin, analgesia, and sedation.146–148 If medical management fails to improve shock states secondary to cardiac failure, use of mechanical support—such as a ventricular assist device or extracorporeal membrane oxygenation (ECMO)— may be indicated Cardiac transplantation has become an important CHAPTER 34 Shock States 361 tool for treating patients with severe myocardial dysfunction who otherwise would die of their heart disease and myxedema coma Appropriate replacement with hydrocortisone and thyroid hormone, respectively, is imperative Obstructive Shock Septic Shock Identification of the cause of obstructive shock will guide therapy The treatment for the following obstructive shock states will be highlighted: cardiac tamponade, tension pneumothorax, ductaldependent heart lesions, and pulmonary embolism (PE) The definitive treatment for cardiac tamponade is the removal of pericardial fluid or air by pericardiocentesis, which may need surgical drainage by either thoracotomy or a subxiphoid limited approach The removal of even a small volume of fluid can lead to a rapid improvement in blood pressure and cardiac output Medical management is not a substitute for drainage but may avert a catastrophe until pericardiocentesis or surgical drainage can be safely performed The principles of medical management include blood volume expansion to maintain venoatrial pressure gradients and inotropic agents Treatment of a tension pneumothorax includes immediate needle decompression as a temporizing measure to reduce intrapleural pressure and restore venous return to the right side of the heart Thoracostomy should then be performed to ensure continued decompression As with cardiac tamponade, medical management with fluid boluses to maintain a venous return to the heart can be used to maintain systemic perfusion during decompression and thoracostomy As noted earlier, infants with ductal-dependent cardiac lesions (such as critical aortic stenosis, aortic arch interruption, or juxtaductal coarctation of the aorta) depend on patency of the ductus arteriosus to provide adequate lower body perfusion A high index of suspicion must be maintained for infants who present in shock in the first month of life; continuous PGE1 infusion should be initiated as the diagnostic evaluation is performed Treatment of obstructive shock secondary to PE will depend on stability following initial resuscitation Initial resuscitation is like all other forms of shock: intubation/mechanical ventilation, fluid resuscitation, and vasoactive support If the patient is hemodynamically stable after this initial resuscitation, then immediate anticoagulation should be initiated with unfractionated heparin in cases with serious clinical concern for PE (given no contraindications to therapy) In patients who remain hemodynamically unstable after initial resuscitation, the use of thrombolytic therapy should be initiated or, if contraindicated, emergent embolectomy should be considered Evidence-based algorithms for the resuscitation of septic children and neonates are easy to use and have been shown to improve outcomes across diverse patient populations.58,149 The emphasis during the first hour of resuscitation is directed to age-appropriate goals of heart rate, blood pressure, perfusion pressure (mean arterial pressure, central venous pressure), and capillary refill time of seconds or less PRBCs may be used if the hematocrit is less than 30% because RBC transfusion increases oxygen delivery to the tissues However, the expansion of oxygen-carrying capacity may not improve oxygen consumption.150 Transfusion of PRBCs as part of a strategy to increase mixed Svo2 to greater than 70% resulted in improved outcome in pediatric septic shock.62 Timely administration of broad-spectrum antibiotic therapy is a crucial component in the septic shock bundle for the treatment of septic shock Whenever possible, blood, urine, and samples from other potentially infected sites should be sent for culture and susceptibility testing before initiation of antibiotic therapy However, obtaining these cultures should never delay appropriate empiric antimicrobial therapy Delay in treating with appropriate antibiotics is associated with increased mortality and prolonged organ failure Source control is imperative; therefore, removal or control of microorganisms by surgical debridement and drainage may need to be considered in some cases Distributive Shock Treatment of anaphylaxis includes the administration of intramuscular or subcutaneous epinephrine, albuterol for wheezing, steroids, H2-blockers and removal of the offending agent Fluid resuscitation is imperative for anaphylactic shock Vasoactive medications may be necessary in patients unresponsive to fluid resuscitation In the setting of spinal cord trauma or other causes of neurogenic shock, treatment is focused on immobilization of the spinal cord, neurosurgical consultation, and providing hemodynamic stability through fluid administration and initiation of a peripheral vasoconstrictor (phenylephrine is generally preferred given the predominant a1 effects) Other potential presentations of distributive shock include adrenal crisis Other Therapies Adrenal insufficiency should be suspected in patients with refractory shock resulting from trauma (head or abdominal) or sepsis, who received etomidate, or who have a history of steroid use within the past months.151,152 Direct damage to the hypothalamus, anterior pituitary, or adrenals may result in cortisol deficiency.153,154 Guidelines have been developed for critical illness– related corticosteroid insufficiency diagnosis and management in adults; however, no such data exists for pediatrics.155 Currently, hydrocortisone administration is recommended for the treatment of catecholamine-refractory pediatric septic shock in patients at risk for absolute adrenal insufficiency.58 Extracorporeal life support has been used to support patients of all ages with shock Using the keyword “shock,” we searched the Extracorporeal Life Support Organization database to determine the use of ECMO in patients with refractory pediatric shock from 1985 through December 2018 Of the 3813 pediatric patients who underwent ECMO for refractory shock, 56% were year old or younger The overall mortality was 55%, suggesting that ECMO is a potentially lifesaving tool in refractory septic shock Therefore, patients in refractory shock may benefit from a timely transfer to an ECMO referral center for further evaluation Thrombocytopenia-associated multiple-organ failure is among a spectrum of syndromes associated with disseminated microvascular thromboses that include disseminated intravascular coagulopathy, thrombotic thrombocytopenic purpura (TTP), and hemolytic uremic syndrome (HUS).156 Therapeutic plasma exchange (TPE) is a standard therapy for patients with TTP/HUS because it replaces a disintegrin and metalloprotease with thrombospondin motifs 1, type 13 (ADAMTS-13), and removes unusually large molecular weight multimers of von Willibrand factor ... monophosphate (cGMP; Table 34.2) Phosphodiesterase inhibitors increase cGMP by preventing its degradation within the cell (see Chapter 31) Vasopressin causes vasoconstriction by direct stimulation of vascular... substrate to prevent catabolism, to ensure adequate hydration, and to correct metabolic derangements This may include the use of total parenteral nutrition, intravenous lipids, and concurrent use of... ventricular diastolic volume, having beneficial effects on both pulmonary and systemic capillary pressure This should be reflected in decreased edema, reduced myocardial wall stress, and improved diastolic