Shock

ShockPhoebe Yager, MD,*

Natan Noviski, MD

Author Disclosure

Drs Yager and Noviski

have disclosed no

financial relationships

relevant to this

article. This

commentary does not

contain a discussion

of an unapproved/

investigative use of a

commercial product/

device.

Objectives After completing this article, readers should be able to:1. Describe the basic pathophysiology of shock.2. Characterize the various causes of shock and recognize their clinical presentations.3. Discuss the importance of early, goal-directed treatment of shock.4. Know the guidelines for the type and volume of fluid to be infused initially in

hypovolemic or septic shock.5. Choose the correct drug for the initial management of septic versus cardiogenic shock.6. Be familiar with some of the recent therapies under investigation for the treatment of

shock.

IntroductionA 9-month-old girl presents to the emergency department (ED) with a 4-day history of profusediarrhea and poor oral intake. On physical examination, she appears irritable. Her respira-tory rate (RR) is 70 breaths/min, heart rate (HR) is 180 beats/min, and blood pressure (BP)is 80/50 mm Hg. She has cool, mottled extremities, with sluggish capillary refill and weakperipheral pulses. Is this just a case of dehydration or could this be shock?

A 17-year-old boy presents to the EDwith a 1-day history of headache, general malaise, andfevers. On physical examination, he appears confused. He has a temperature of 39.9C, HR of120 beats/min, and BP of 85/28 mmHg. His skin appears plethoric. His extremities are hot,with flash capillary refill and bounding pulses. Is this the same entity that is affecting the

previous patient?A 2-week-old boy presents to the ED with a 1-day history

of poor feeding. On physical examination, he is difficult toarouse. His RR is 80 breaths/min, HR is 220 beats/min,and BP is undetectable. He appears cyanotic and has coldextremities and a 5-second capillary refill time. Is this the sameentity as seenwith the other two patients?How should you proceed?

All three scenarios describe patients in various stages ofshock, the first due to hypovolemic shock, the second due toseptic shock, and the third due to cardiogenic shock.

The presentation of shock may vary, depending onthe cause and stage of illness, although the pathophysiologyand general management are similar. Prompt recognition ofshock followed by early, goal-directed therapy and frequentreassessment are paramount to a successful outcome.

Definition and PathophysiologyShock is a life-threatening state that occurs when oxygenand nutrient delivery are insufficient to meet tissue metabolicdemands. The crisis may occur when a disease compro-mises any of the factors that contribute to oxygen andnutrient delivery. Familiarity with a few simple equations iskey not only to understanding the myriad factors that maycontribute to shock but to understanding how the body

*Instructor in Pediatrics, Harvard Medical School; Pediatric Intensivist, MassGeneral Hospital for Children, Boston, Mass.Associate Professor of Pediatrics, Harvard Medical School; Chief, Pediatric Critical Care Medicine, MassGeneral Hospital forChildren, Boston, Mass.

Abbreviations

ACCM: American College of Critical Care MedicineALCAPA: anomalous left coronary artery from the

pulmonary arteryALI: acute lung injuryARDS: acute respiratory distress syndromeBP: blood pressureCO: cardiac outputCVP: central venous pressureECMO: extracorporeal membrane oxygenationED: emergency departmentHgb: hemoglobinHR: heart ratePALS: Pediatric Advanced Life SupportPVR: pulmonary vascular resistancerhAPC: recombinant human activated protein CRR: respiratory rateSIRS: systemic inflammatory response syndromeSV: stroke volumeSVR: systemic vascular resistance

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attempts to compensate for the condition and how theclinician may intervene to reverse shock.

Oxygen delivery (DO2) is determined by cardiac out-put (CO) and the arterial content of oxygen (CaO2):

DO2 (mL/min)CO (L/min)CaO2 (mL/L)

Cardiac output is the product of stroke volume (SV)and HR:

CO (L/min)SV (L)HR/min

Stroke volume is determined by:

Preload: the amount of filling of the ventricle at end-diastole

Afterload: the force against which the ventricle mustwork to eject blood during systole

Contractility: the force generated by the ventricle dur-ing systole

Lusitropy: the degree of myocardial relaxation duringdiastole

Heart rate variability relies on an intact autonomicnervous system and a healthy cardiac conduction system.

Arterial oxygen content also dictates oxygen deliveryand is determined by hemoglobin (Hgb), oxygen satu-ration (SaO2), and the partial pressure of oxygen (PaO2),as follows:

CaO2 (ml/L){[Hgb (g/dL)1.34 (mL O2/g Hgb)(SaO2/100)](PaO20.003 mL O2/mmHg/dL)}10 dL/L

For example, for a patient who has an Hgb value of15 g/dL, PaO2 of 100 torr, CO of 5 L/min, and SaO2 of98%, the DO2 can be calculated as follows:

CaO2{[15 g/dL1.34 mL O2/g Hgb(98/100)](1000.003 mL O2/mm Hg/dL)}10 dL/L

CaO2200 mL/L

DO25 L/min200 mL/L1,000 mL/min

It is important to recognize that oxygen is not distrib-uted uniformly to the body. Modulation of systemicvascular resistance (SVR) in different vascular beds is oneof the bodys primary compensatory mechanisms toshunt blood preferentially to vital organs such as theheart and brain. In this way, an increase in SVR maymaintain a normal blood pressure even in the face ofinadequate oxygen delivery. In other words, hypotensionneed not be present for a child to be in shock.

Shock refers to a dynamic state ranging from early,compensated shock to irreversible, terminal shock. Dur-ing the earliest stage of shock, vital organ function is

maintained by a number of compensatory mechanisms,and rapid intervention can reverse the process. If unrec-ognized or undertreated, compensated shock progressesto decompensated shock. This stage is characterized byongoing tissue ischemia and damage at the cellular andsubcellular levels. Inadequate treatment leads to terminalshock, defined as irreversible organ damage despite ad-ditional resuscitation.

Classification and Clinical PresentationHypovolemic Shock

Hypovolemic shock is the most common form of shockoccurring in children around the world. Diarrheal ill-nesses are the cause in most of these patients. Some othercauses include bleeding, thermal injury, and inappropri-ate diuretic use.

Signs and symptoms of hypovolemic shock includetachycardia, tachypnea, and signs of poor perfusion, in-cluding cool extremities, weak peripheral pulses, sluggishcapillary refill, skin tenting, and dry mucous membranes.Orthostatic hypotension may be an early sign. As thebodys ability to compensate reaches its limit, hypoten-sion develops, along with additional signs of hypoperfu-sion and end-organ damage. At this stage, the clinicalfindings include weak central pulses, poor urine output,mental status changes, and metabolic acidosis.

Cardiogenic ShockCardiogenic shock refers to failure of the heart as a pump,resulting in decreased cardiac output. This failure may bedue to depressed myocardial contractility, arrhythmias,volume overload, or diastolic dysfunction. Depressedmyocardial contractility may be seen with primary neuro-muscular disorders or may be acquired in any numberof settings, such as infection, following exposure to atoxin, or when a patient suffers a metabolic derangementsuch as severe hypocalcemia or hyperkalemia.Myocardialischemia due to inadequate coronary perfusion occurswith a number of congenital cardiac lesions as well aswith dysrhythmias that may compromise cardiac outputseverely.

Hypoplastic left heart syndrome, aortic stenosis, andcoarctation of the aorta are three life-threatening con-genital lesions that obstruct outflow from the left heart.Systemic outflow and coronary perfusion in these condi-tions depend on right-to-left flow from the pulmonaryartery to the aorta via a patent ductus arteriosus. Tri-cuspid atresia, pulmonary atresia, and tetralogy of Fallotare three cyanotic congenital lesions that obstruct out-flow from the right heart. In these lesions, adequatepulmonary blood flow depends on a left-to-right shunt

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312 Pediatrics in Review Vol.31 No.8 August 2010


across a patent ductus arteriosus. Infants born withductal-dependent congenital heart disease often presentwithin the first 2 weeks after birth, by which time theductus arteriosus has closed.

Infants born with congenital lesions resulting in sig-nificant left-to-right shunts (eg, ventricular septal de-fects, truncus arteriosus, and anomalous left coronaryartery from the pulmonary artery [ALCAPA]) typicallypresent between 6 weeks and 3 months of age as pul-monary vascular resistance (PVR) falls. This change inresistance results in a steal phenomenon whereby bloodpreferentially flows to the pulmonary bed and awayfrom the systemic bed, leading to inadequate cardiacoutput. In the case of ALCAPA, as PVR falls, blood flowsto the pulmonary bed and away from the myocardium.Coronary ischemia develops, resulting in poor contrac-tility, diminished cardiac output, and life-threateningdysrhythmias.

Other types of dysrhythmias (eg, supraventriculartachycardia) infections causing myocarditis or pericardi-tis, and congenital cardiomyopathies can present at anytime and should be part of the differential diagnosis forany child presenting with signs of poor perfusion.

Infants and children who have cardiogenic shock of-ten present with lethargy, poor feeding, tachycardia,and tachypnea. They typically appear pale and have coldextremities and barely palpable pulses. In the case ofcritical coarctation of the aorta, the infant may haveabsent femoral pulses and a significantly lower BP in thelower extremities compared with the right upper extrem-ity. Oliguria is present.

Initially, it may be impossible to differentiate cardio-genic shock from septic shock. Findings more specific tocardiogenic shock include a gallop rhythm, rales, jugularvenous distension, and hepatomegaly. Chest radiogra-phy reveals cardiomegaly and pulmonary venous conges-tion. Unlike other forms of shock in which central ve-nous pressure (CVP) is low, in cardiogenic shock, CVP iselevated above 10 cm H2O. Although it is imperative toobtain electrocardiography and echocardiography im-mediately if there is any suspicion of cardiogenic shock,empiric treatment for possible septic or cardiogenicshock should not be delayed.

Two noncardiac conditions that can lead to cardio-genic shock are bilateral pneumothoraces and cardiactamponade. Both prevent diastolic filling of the heart,which leads to decreased SV and poor CO. These disor-ders should be suspected in the patient presenting withsigns of poor perfusion accompanied by a narrow pulsepressure and, in the case of tamponade, muffled hearttones on auscultation.

Distributive or Neurogenic ShockDistributive shock is caused by derangements in vasculartone that lead to end-organ hypoperfusion. This out-come is seen with anaphylaxis, an immunoglobulinE-mediated hypersensitivity reaction in which mast cellsand basophils release histamine, a potent vasodilator, andthere is massive production of other potent vasodilators,including prostaglandins and leukotrienes. Spinal cordtrauma and spinal or epidural anesthesia also can causewidespread vasoplegia due to loss of sympathetic tone.This situation sometimes is referred to as neurogenicshock. Unlike other forms of shock, patients who expe-rience neurogenic shock exhibit hypotension withoutreflex tachycardia. Finally, septic shock in some childrenpresents with vasoplegia.

Septic ShockIn 1992, the American College of Chest Physicians andthe Society of Critical Care Medicine formally definedsepsis and its related syndromes. They introduced theimportant concept of a systemic inflammatory responsesyndrome (SIRS), whereby the body responds to vari-ous insults (infection, trauma, thermal injury, acute re-spiratory distress syndrome) with overwhelming inflam-mation resulting in hypo- or hyperthermia, tachycardia,tachypnea, and either an elevated or depressed whiteblood cell count. When SIRS is triggered by an infection,it is defined as sepsis, and when this condition is associ-ated with organ dysfunction, it is referred to as severesepsis. Septic shock in the pediatric population is charac-terized by sepsis accompanied by tachycardia and signs ofinadequate perfusion. (1)

The host response to infection is one of the primarydeterminants of whether an individual develops septicshock. Endotoxin released by gram-negative rods andantigens presented by various other pathogens set inmotion in the host an inflammatory cascade resulting inthe activation of lymphocytes and the release of pro-inflammatory cytokines such as tumor necrosis factor,interleukin-1 (also known as endogenous pyrogen),and interleukin-6. These cytokines activate other pro-inflammatory cytokines and mediators of sepsis, includ-ing nitric oxide (a potent vasodilator), platelet-activatingfactor, prostaglandins, thromboxane, and leukotrienes.Overproduction of these mediators disrupts the deli-cate balance between pro- and anti-inflammatory factorsand can lead to unchecked inflammation and septicshock.

Cold versus warm shock refers to the two pri-mary clinical presentations of septic shock. Cold shockdescribes the pattern of signs and symptoms seen with

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low CO and high SVR. This clinical picture includestachycardia, mottled skin, cool extremities with pro-longed capillary refill, and diminished peripheral pulses.Blood pressure may be normal. Most septic children havethis presentation. In contrast, most adults and somechildren present in warm shock due to high cardiacoutput and low SVR. This scenario includes tachycardia,plethora, warm extremities with flash capillary refill,bounding pulses, and a widened pulse pressure. Thepreviously noted patterns may interchange in the samepatient, during the same illness. Therefore, frequentclinical assessment is required. The pattern of shock inneonates typically is more one of persistent pulmonaryhypertension with right ventricular failure.

TreatmentsAirway

Regardless of the cause of shock, initial resuscitationmust be guided by the ABCs (airway, breathing, circu-lation). Supplemental oxygen should be administeredimmediately. Intubation is indicated for the patientwhose mental status is altered, who is unable to protecthis or her airway, or who has impending respiratoryfailure. In addition, early intubation should be consid-ered to decrease metabolic demands, help regulate ven-tilation and temperature, and if needed, allow for theadministration of sedation and analgesia for invasive pro-cedures. Positive-pressure ventilation also is a powerfultool to decrease afterload to the left heart of the patientpresenting in cardiogenic shock.

Patients suffering shock may develop acute lung in-jury (ALI) or acute respiratory distress syndrome(ARDS). ALI and ARDS aremarked by increasingly pooroxygenation (PaO2/FiO2300 in ALI and PaO2/FiO2200 in ARDS) and ventilation, despite escalatingventilatory support and worsening bilateral infiltrateson chest radiograph without signs of left-sided heartfailure. It is important to recognize ALI or ARDS andrespond appropriately with a lung-protective strategy ofventilation.

AccessObtaining rapid vascular access with at least two wide-bore peripheral intravenous lines is critical to the timelytreatment of circulatory shock. Obtaining such accesscan be challenging because most patients present withcool, poorly perfused extremities. If sufficient percu-taneous venous access cannot be obtained quickly, theNeonatal Resuscitation Program and Pediatric AdvancedLife Support (PALS) guidelines recommend placementof an umbilical venous catheter (neonates only) or intra-

osseous needle (infants and children). (2) Central venousaccess provides more stable, long-term access and shouldbe obtained in patients who have fluid-refractory shockand who require titration of vasopressors and inotropes.In addition, a central venous catheter enables the clini-cian to monitor CVP. This measurement can be helpfulfor diagnosing cardiogenic shock and guiding the clini-cian during volume administration in all forms of shock.

Sedatives and AnalgesicsMany of the sedating medications used for intubationand other invasive procedures in children have propertiesthat may exacerbate shock. Benzodiazepines, opioids,and propofol can decrease the BP and must be usedjudiciously. Etomidate has been shown to induce adrenalinsufficiency. The 2007 updated clinical practice param-eters for hemodynamic support of pediatric and neonatalseptic shock from the American College of Critical CareMedicine (ACCM) recommend against the use of eto-midate and for the use of atropine and ketamine forchildren (experience with ketamine use in neonates wasinsufficient to recommend its use in this age group). (3)

Fluid TherapyRapid volume resuscitation is the single most importantintervention to help restore adequate organ perfusion inpatients presenting with various forms of hypovolemicshock. Volume resuscitation should occur early and begoal-directed. The American Heart Association and PALSguidelines recommend an initial rapid bolus of 20 mL/kgof isotonic fluid followed by immediate reassessmentand titration of additional fluid administration to goals ofnormal BP and perfusion (capillary refill 2 seconds,1 mL/kg per hour urine output, normal mental status)or until signs of fluid overload occur (rales, increasedwork of breathing, gallop rhythm, hepatomegaly, CVPincreases without additional hemodynamic improve-ment). Patients may require up to 200mL/kg of isotonicfluid within the first hour, particularly in cases of vascularparalysis, to restore adequate perfusion.

The 2007 ACCM clinical practice guidelines for treat-ment of neonatal and pediatric septic shock recommendfurther that volume resuscitation beyond the first hourbe titrated not only to signs of improved perfusion andnormal blood pressure, but to an age-appropriate perfu-sion pressure (approximately 55 to 65 mmHg), a mixedvenous saturation greater than 70%, and a cardiac indexgreater than 3.3 L/min/m2 and less than 6.0 L/min/m2. The Figure provides an algorithm for goal-directedmanagement of hemodynamic support in septic shockbased on these guidelines.

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Fluid resuscitation in infants and children who havecardiogenic shock should be approached carefully be-cause these patients may be hypo-, hyper-, or euvolemic.In the euvolemic or hypervolemic patient, volume load-ing the failing heart may exacerbate pump failure andcontribute to pulmonary congestion. Frequent clinicalassessment is required during initial fluid resuscitationfor patients who have potential cardiogenic shock.Ideally, a central venous line should be placed to monitorCVP and to assist in adjusting therapy.

AntibioticsBroad-spectrum antibiotics based on age should be ad-ministered within the first hour of presentation whensepsis is suspected. Because it can be difficult to differen-tiate septic shock from cardiogenic shock in the neonate,this age group always should be treated with antibiotics.Appropriate specimens for blood, urine, and cerebrospi-nal fluid cultures should be obtained before antibioticadministration, although difficulty obtaining samplesshould not delay administration.

Crystalloid Versus ColloidThe 2007 ACCM clinical practiceguidelines for treatment of neona-tal and pediatric septic shock rec-ommend either isotonic crystalloidor 5% albumin for volume resusci-tation in the first hour. Beyond thefirst hour, the guidelines recom-mend crystalloid for patients whohave Hgb values greater than10 g/dL (100 g/L) and packed redblood cell transfusion for thosewhose Hgb values are less than10 g/dL (100 g/L). In addition torestoring circulating volume,packed red blood cells also serve toincrease oxygen-carrying capacity.Fresh frozen plasma administeredas an infusion is recommended forpatients who have a prolonged In-ternational Normalized Ratio.

Cardiovascular SupportIn cases of fluid-refractory shockand cardiogenic shock, cardiovas-cular agents are necessary. Thechoice of agent depends largely onthe underlying cause and the clini-cal presentation of shock. Selectionof an appropriate agent is based on

its known effects on inotropy, chronotropy, SVR, andPVR. The Table provides a summary of cardiovascularmedications used in shock.

The 2007 ACCM guidelines recommend temporaryinstillation of cardiovascular agents through a peripheralintravenous line until central access can be obtained.

INOTROPIC AGENTS. Dopamine, dobutamine, andepinephrine work on beta1 receptors in the myocardiumto increase cytoplasmic calcium concentration and en-hance myocardial contractility. Dopamine is consideredfirst-line therapy for patients who have fluid-refractory,hypovolemic, or septic shock. However, infants youngerthan 12 months of age may not respond effectively todopamine, in which case epinephrine should be consid-ered. Epinephrine also should be added for childrenexperiencing dopamine-refractory hypovolemic or septicshock, defined as persistent hypotension despite at least60 mL/kg volume and dopamine infusing at 10 mcg/kgper minute. For patients who have cardiogenic shock,early inotropic support rather than large-volume resusci-

Figure. Algorithm for goal-directed management of hemodynamic support in septicshock. Adapted from the 2007 ACCM clinical practice parameters for hemodynamicsupport of pediatric and neonatal septic shock. AIadrenal insufficiency, BPbloodpressure, CIcardiac index, CVPcentral venous pressure, DAdopamine,Dobutdobutamine, ECMOextracorporeal membrane oxygenation, Epiepinephrine,IVintravenous, iNOinhaled nitric oxide, IOintraosseous, LVleft ventricle,NLnormal, PGE1prostaglandin E1, RVright ventricle, ScvO2mixed venous oxygensaturation, UVCumbilical venous catheter

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tation is required. Dopamine, dobutamine, and epineph-rine are acceptable therapies.

VASOPRESSORS. All of the previously discussed ino-tropic agents also have vasoactive properties that mustbe considered when selecting an appropriate agent andtitrating the dose. At higher doses, for example, dopa-mine and epinephrine have increasing alpha-adrenergiceffects, leading to peripheral vasoconstriction and in-creased SVR. Dobutamine, on the other hand, causesperipheral and pulmonary vasodilation due to beta2-adrenergic effects. This effect may be deleterious in thepatient who has low CO and low SVR but beneficial inthe child presenting with low CO and high SVR or theneonate experiencing acute cardiac failure and pulmo-nary hypertension.

Phenylephrine is a pure alpha-agonist used to achievesystemic vasoconstriction in distributive shock and septicshock presenting with high CO and low SVR. Norepi-

nephrine is a more potent vasoconstrictor used in thesame setting. At higher doses, norepinephrine also actson beta receptors, exerting inotropic and chronotropiceffects. Both drugs should be avoided in cardiogenicshock due to their powerful effect of increasing afterload.

Arginine-vasopressin and its synthetic analog, terli-pressin, have been investigated for their potential use invasodilatory shock refractory to first-line catecholamineagents. Given the limited pediatric experience with theseagents for the treatment of catecholamine-refractoryvasodilatory shock, no recommendation can be made atthis time, and their use should be considered on a case-by-case basis. (4)

VASODILATORS. Nitroprusside is a pure vasodilatorused to decrease afterload and improve coronary perfu-sion in neonates and children who have cardiogenicshock. Its use is limited by the need for adequate perfu-

Table. Cardiovascular Medications for the Treatment of ShockMedication Site of Action Clinical Effects Uses in Shock

Dopamine >2 1inotropy, 1HR, 2SVR,2PVR

Cardiogenic shock Septic shock with 2CO, 1SVR

Epinephrine > 1inotropy, 1HR, 1SVR Septic shock with 2CO, 2SVR Cardiogenic shock Anaphylactic shock

Norepinephrine >> 1SVR, 1inotropy, 1HR Hypovolemic shock (temporizing measureonly during volume expansion)

Distributive shock Septic shock with 1CO, 2SVR

Milrinone PDE III inhibitor 1inotropy, 2SVR, 2PVR,1lusitropy

Cardiogenic shock with stable BP Septic shock with 2CO, 1SVR

Phenylephrine 1>2 1SVR Septic shock with 1CO, 2SVRVasopressin V1, V2 1SVR Distributive shock

Septic shock with 1CO, 2SVRProstaglandin E1 PGE1 Dilation of ductus arteriosus Cardiogenic shock in neonate with

suspected ductus-dependent lesionNitroprusside arteries>veins 2SVR, 1coronary perfusion Cardiogenic shockInhaled nitric oxide pulmonary vessels 2PVR Cardiogenic shock with PHTN, RV failureLevosimendan, enoximone cardiac troponin C,

ATP-dependentpotassiumchannels incardiacmyocytes

1inotropy, ?cardioprotection Experimental use in cardiogenic shock

ATPadenosine triphosphate, BPblood pressure, COcardiac output, HRheart rate, PDEphosphodiesterase, PGEprostaglandin E,PHTNpulmonary hypertension, PVRpulmonary vascular resistance, RVright ventricle, SVRsystemic vascular resistance

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sion pressure, which sometimes is attained by the con-comitant use of dopamine or epinephrine.

Prostaglandin E1 is a potent vasodilator that relaxessmooth muscle in the ductus arteriosus to maintain pa-tency. It should be initiated immediately in cases ofsuspected cardiogenic shock presenting within the first2 weeks after birth until a ductal-dependent lesion hasbeen ruled out by echocardiography. Prostaglandin E1also may affect systemic vasodilation, and it may be nec-essary to add dopamine to maintain adequate systemicperfusion. In addition, prostaglandin E1 can cause ap-nea, necessitating intubation and mechanical ventilation.

Inhaled nitric oxide is a selective pulmonary vasodila-tor that may be considered in the treatment of cardio-genic shock involving right ventricle failure. This agentworks via second messenger cGMP to relax vascularsmooth muscle and produce vasodilation. With the ad-vent of inhaled nitric oxide therapy to treat neonateswho have cardiogenic shock due to persistent pulmonaryhypertension, many patients now can recover withoutthe need for extracorporeal membrane oxygenation(ECMO) support.

INODILATORS. Milrinone is a phosphodiesterase IIIinhibitor that has gained popularity in the treatment ofcardiogenic shock due to its positive inotropic and lusi-tropic effects as well as its ability to reduce systemic andpulmonary afterload through vasodilation. This agentworks by preventing the breakdown of cAMP, leading toan increase in intracellular calcium.

Levosimendan and enoximone are two of the newestinodilators being investigated for their use in cardiogenicshock due to their dual action as positive inotropes aswell as coronary and systemic vasodilators. Unlike milri-none, these agents work by increasingmyocyte sensitivityto calcium rather than by increasing intracellular concen-trations of calcium. They mediate vasodilation throughactivation of adenosine triphosphate-dependent potas-sium channels in vascular smooth muscle. Activation ofthese channels in cardiomyocytes also may have a cardio-protective effect following an ischemic insult to the heart.(5) To date, research in children has been limited, butthere have been reports of decreased demand for cate-cholamine infusion and improved myocardial contractil-ity with the addition of levosimendan in neonates andchildren experiencing acute heart failure. (5)(6)

CorticosteroidsThe 2008 Surviving Sepsis Campaign guidelines rec-ommend consideration of stress-dose corticosteroids(hydrocortisone 50 mg/m2 per 24 hours) in pediatric

patients who have catecholamine-resistant septic shockand suspected or proven adrenal insufficiency. (7) Inchildren, absolute adrenal insufficiency is considered at arandom cortisol concentration less than 18 mcg/dL(496.6 nmol/L). An increase of less than 9 mcg/dL(248.3 nmol/L) following cosyntropin (synthetic deriv-ative of corticotropin) stimulation test is considered rel-ative adrenal insufficiency, and treatment is debatable. Inneonates, adrenal insufficiency is defined as a peak corti-sol value less than 18 mcg/dL (496.6 nmol/L) follow-ing cosyntropin test or basal cortisol value less than18 mcg/dL (496.6 nmol/L) in an appropriatelyvolume-loaded patient requiring epinephrine. In addi-tion to patients known to have pituitary or adrenal ab-normalities, patients at risk for adrenal insufficiency in-clude those who have a history of corticosteroid usewithin the last 6 months and those suffering severe septicshock accompanied by purpura fulminans andWaterhouse-Friderichsen syndrome. Indications for pos-sible corticosteroid use are the same according to the2007 ACCM guidelines, although the suggested dose ofhydrocortisone ranges from 2 mg/kg per day for stresscoverage to 50mg/kg per day to reverse shock. The datato support these recommendations are weak, and a ran-domized, controlled study is needed.

Corticosteroids also should be administered to pa-tients who have distributive shock caused by anaphylaxisor spinal trauma. In addition, antihistamines may help pre-vent additional mast cell degranulation in anaphylacticshock.

Glycemic ControlChildren presenting in shock often have a number ofmetabolic derangements, including hyper- or hypo-natremia, hypocalcemia, and hypoglycemia. These dis-orders should be suspected and treated promptly. How-ever, persistent hyperglycemia often is seen beyond theinitial resuscitation of shock and has been associated withincreased severity of illness and increased mortality in hos-pitalized patients. Tight glycemic control (150 mg/dL[8.3 mmol/L]) in critically ill adults has been advocated.However, to date no pediatric studies have analyzed theeffects of tight glycemic control with insulin. Due to alack of data and the known risk of hypoglycemia inchildren dependent on intravenous glucose, the 2008Surviving Sepsis Campaign guidelines and 2007 ACCMparameters make no recommendations beyond the use ofmaintenance fluid containing 10% glucose.

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Activated Protein CSevere sepsis and septic shock often are accompanied bya significant disruption of the delicate balance betweenpro- and anticoagulants, leading to life-threatening dis-seminated intravascular coagulation. Uncontrolled coag-ulation ultimately consumes procoagulants, resulting inbleeding. Activated protein C is an anticoagulant thathelps regulate coagulation and inflammation, and it hasbeen found to be deficient in patients experiencing septicshock. Adult studies have shown that treatment withrecombinant human activated protein C (rhAPC) re-duces mortality with only a small increase in risk ofbleeding. However, a large randomized, controlled trialof rhAPC in children was halted prematurely after in-terim analysis of the data from 474 enrolled patientsrevealed no difference in mortality. (8) Due to the inher-ent risk of bleeding and the absence of proven efficacy,the Surviving Sepsis Campaign guidelines recommendagainst the use of rhAPC in children who have septicshock.

Extracorporeal Life SupportAlthough ECMO has a definitive role in the treatment ofcardiogenic shock refractory to maximum pharmaco-logic support, its role in the treatment of refractory septicshock has been less clear. Over the past decade, morecenters have begun to use ECMO as rescue therapy forseptic shock with circulatory collapse and multiorganfailure. The current ECMO survival rate for term new-borns who have septic shock is 80%; that for olderchildren is 50%. Based on limited retrospective data, theSurviving Sepsis Campaign guidelines and the ACCMparameters for support of pediatric and neonatal septicshock suggest that ECMO be considered only in cases ofrefractory septic shock or respiratory failure that cannotbe managed adequately with conventional support.

References1. SCCM/ESICM/ACCP/ATS/SIS. International sepsis defini-tions conference. Crit Care Med. 2003;31:125012562. AmericanHeart Association (AHA) guidelines for cardiopulmo-nary resuscitation (CPR) and emergency cardiovascular care (ECC)

of pediatric and neonatal patients: PALS. Pediatrics. 2006;117:e1005e10283. American College of Critical Care Medicine. Clinical practiceparameters for hemodynamic support of pediatric and neonatalseptic shock: 2007 update from the American College of CriticalCare Medicine. Crit Care Med. 2009;37:6666884. Meyer S, Gortner L, McGuire W, et al. Vasopressin incatecholamine-refractory shock in children. Anesthesia. 2008;63:2282345. De Luca L, Colucci WS, Nieminen MS, et al. Evidence-baseduse of levosimendan in different clinical settings. Eur Heart J.2006;27:190819206. Namachivayam P, Crossland DS, Butt WW, Shekerdemian LS.Early experience with levosimendan in children with ventriculardysfunction. Pediatr Crit Care Med. 2006;7:4454487. Surviving Sepsis Campaign. International guidelines for man-agement of severe sepsis and septic shock: 2008. Crit Care Med.2008;36:2963278. Nadel S, Goldstein B, Williams MD, et al. Drotrecogin alfa(activated) in children with severe sepsis: a multicentre phase IIIrandomized controlled trial. Lancet. 2007;369:8368439. Han YY, Carcillo JA, Dragotta MA, et al. Early reversal ofpediatric-neonatal septic shock by community physicians is associ-ated with improved outcome. Pediatrics. 2003;112:793799

Summary Based on strong research evidence (2), if sufficient

peripheral access cannot be obtained quickly,placement of an intraosseous needle should beconsidered in the initial management of shock.

Based on strong research evidence (9), fluidresuscitation for hypovolemic and septic shockshould start immediately and the volume be titratedto attain specific goals indicating improvedperfusion.

Based on some research evidence and consensus (3),inotropic support should be administered through aperipheral intravenous line until central access canbe obtained to avoid delay in restoration ofadequate perfusion pressure.

Based on weak research evidence and consensus (7),corticosteroid therapy is suggested only for patientswho have catecholamine-resistant septic shock andsuspected or proven adrenal insufficiency.

Based on strong research evidence (8), rhAPC shouldnot be used to treat children who have septic shockassociated with disseminated intravascularcoagulopathy.

critical care shock



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1. A 3-day-old girl presents with difficulty breathing and looking dusky for the past 6 hours. The infant was born after anormal vaginal delivery and weighed 3.2 kg at birth. Examination reveals a pale/grayish-looking child whose respira-tions are labored, accompanied by grunting. Rectal temperature is 36.0C, respiratory rate is 80 breaths/min, heart rateis 160 beats/min, and blood pressure is 50/30 mm Hg. Peripheral pulses are poor but equal in all extremities. Chestauscultation reveals a gallop rhythm and normal breath sounds. Her abdomen is distended, and the liver is palpated4 cm below the right costal margin. No improvement is noted after an intravenous bolus of 20 mL/kg saline, endo-tracheal intubation, and mechanical ventilation with 40% oxygen. Antibiotics are administered. Pulse oximetry shows90% oxyhemoglobin saturation. Blood gas analysis shows pH of 7.12, PCO2 of 60 torr, and PO2 of 74 torr. Which ofthe following is the next most appropriate step?A. Administer sodium bicarbonate.B. Begin infusion of norepinephrine.C. Increase FiO2 to increase oxyhemoglobin saturation above 95%.D. Initiate infusion of prostaglandin E1.E. Initiate inhaled nitric oxide therapy.

2. A 3-month-old boy presents with difficulty breathing and looking dusky for the past 6 hours. The infant has haddifficulty feeding and episodes of high-pitched cry several times a day for the past 2 weeks. Examination reveals apale/grayish-looking child whose respirations are labored, accompanied by grunting. Rectal temperature is 36.0C,respiratory rate is 50 breaths/min, heart rate is 160 beats/min, and blood pressure is 90/60 mm Hg. His extremities arecold, with a capillary refill time of 4 seconds. Chest auscultation reveals a gallop rhythm and bilateral wheezes. Theliver is palpated 4 cm below the right costal margin. Chest radiograph shows moderate cardiomegaly and pulmonarycongestion. Electrocardiography shows prominent Q waves; ST segment elevation; and inverted T waves in leads I, aVL,V5, and V6. Which of the following mechanisms is the best explanation for these manifestations?A. Closure of the ductus arteriosus.B. Decrease in pulmonary arterial pressure.C. Decreased ventricular lusitropy.D. Inflammation of cardiac myocytes.E. Pericardial tamponade.

3. A 12-year-old boy presents after being struck by a car while crossing a street. He is unresponsive, with a respiratoryrate of 15 breaths/min, heart rate of 50 beats/min, and blood pressure of 76/36 mm Hg. Physical examination revealsbruises and abrasions across the neck, chest, and abdomen. Chest auscultation documents clear breath sounds withequal air entry bilaterally. Rapid sequence intubation is performed, followed by mechanical ventilation. Rapid intra-venous infusion of 100 mL/kg 0.9% saline is administered over 1 hour. Repeat assessment shows a heart rate of52 beats/min and blood pressure of 80/40 mm Hg. His extremities are warm with brisk capillary refill time. Which ofthe following is most likely associated with these findings?A. Abdominal solid organ injury.B. Adrenal insufficiency.C. Intracranial hemorrhage.D. Myocardial contusion.E. Sympathetic tone loss.

4. A 5-year-old girl presents with fever and decreasing responsiveness for 12 hours. She is obtunded and moaning in-comprehensibly. Her rectal temperature is 40.0C, respiratory rate is 26 breaths/min, heart rate is 136 beats/min, andblood pressure is 78/50 mm Hg. Her extremities are cool with prolonged capillary refill time. Multiple areas of ecchy-mosis and purpura are noted over her face, trunk, and extremities. After rapid sequence intubation, mechanical venti-lation, intravenous fluid expansion with 0.9% saline (80 mL/kg), and administration of dopamine, epinephrine, anddobutamine, her blood pressure improves to 100/70 mm Hg. Her extremities, however, remain cold with poorperfusion. Which of the following is the next most appropriate therapy?A. Activated protein C.B. Arginine vasopressin.C. Hydrocortisone.D. Phenylephrine.E. 25% albumin.

critical care shock



DOI: 10.1542/pir.31-8-3112010;31;311Pediatrics in Review

Phoebe Yager and Natan NoviskiShock

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DOI: 10.1542/pir.31-8-3112010;31;311Pediatrics in Review

Phoebe Yager and Natan NoviskiShock

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