Septic Shock Rapid Recognition and Initial Resuscitation In

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AuthorsScott L Weiss, MD

Wendy J Pomerantz, MD, MS

Section EditorsAdrienne G Randolph, MD, MSc

Susan B Torrey, MDSheldon L Kaplan, MD

Deputy EditorJames F Wiley, II, MD, MPH

Septic shock: Rapid recognition and initial resuscitation in children

Disclosures

All topics are updated as new evidence becomes available and ourpeer review process is complete.Literature review current through: Apr 2013. | This topic last updated: Feb 19, 2013.

INTRODUCTION Sepsis is a clinical syndrome complicating severe infection that is characterized by systemic inflammation, immune dysregulation,

microcirculatory derangements, and end-organ dysfunction. There is a continuity of severity ranging from sepsis to severe sepsis and septic shock. Severe

sepsis and septic shock are characterized by dysfunction of 2 organ systems and cardiovascular dysfunction, respectively [1]. With increased attention to

rapid recognition, aggressive fluid administration, and early administration of vasoactive agents and antibiotics, pediatric mortality from severe sepsis and

septic shock has decreased markedly [2-7].

The early recognition and initial management of severe sepsis and septic shock in children during the first hour of resuscitation are reviewed here. The

definitions, epidemiology, and clinical manifestations of sepsis in children and ongoing management of children with septic shock are discussed separately.

(See "Systemic inflammatory response syndrome (SIRS) and sepsis in children: Definitions, epidemiology, clinical manifestations, and diagnosis" and

"Septic shock: Ongoing management after resuscitation in children".)

DEFINITION Septic shock refers to sepsis with cardiovascular dysfunction (ie, hypotension, reliance on vasoactive drug administration to maintain a

normal blood pressure, or two of the following: prolonged capillary refill, oliguria, metabolic acidosis, or elevated arterial lactate) that persists despite the

administration of 40 mL/kg of isotonic fluid in one hour. (See "Systemic inflammatory response syndrome (SIRS) and sepsis in children: Definitions,

epidemiology, clinical manifestations, and diagnosis", section on 'Severity'.)

RAPID RECOGNITION A clinical diagnosis of septic shock is made in children who have signs of inadequate tissue perfusion, two or more criteria for the

systemic inflammatory response syndrome (table 1), and suspected or proven infection [8]. Rapid recognition of hemodynamic abnormalities and early

suspicion of infection are essential to achieve favorable outcomes. As an example, in a prospective cohort study of 91 infants and children presenting to

community hospitals with septic shock (defined by hypotension or delayed capillary refill), each hour delay in initiation of appropriate resuscitation or

persistence of hemodynamic abnormalities was associated with a clinically significant increased risk of death (OR 1.5 and 2.3, respectively) [ 4]. (See

"Systemic inflammatory response syndrome (SIRS) and sepsis in children: Definitions, epidemiology, clinical manifestations, and diagnosis", section on

'Definitions' and "Systemic inflammatory response syndrome (SIRS) and sepsis in children: Definitions, epidemiology, clinical manifestations, and diagnosis",

section on 'Severity'.)

Inadequate tissue perfusion Seriously ill patients should undergo urgent evaluation for the following signs of impaired perfusion or shock [ 8,9]:

Fever

Tachycardia or bradycardia

Decreased peripheral pulses compared with central pulses

Mottled or cool extremities

Flash or >3 second capillary refill

Dry mucus membranes, sunken eyes, and decreased urine output

Tachypnea, bradypnea, or apnea

Hypotension

Altered mental status (irritability, anxiety, confusion, lethargy, somnolence, apnea)

Hypothermia (especially neonates)

Tachycardia and tachypnea are common and non-specific findings in young pediatric patients and may be due to fever, anxiety, dehydration, pain/discomfort,

anemia, or agitation. However, persistent tachycardia is a sensitive indicator of circulatory dysfunction and should not be overlooked. If a question exists as to

whether tachycardia is due to circulatory impairment, a fluid bolus is recommended unless there is evidence for cardiac dysfunction (eg, hepatomegaly,

jugular venous distention, S3 gallop, cardiomegaly).

Hypotension is a late sign of cardiovascular dysfunction and shock in pediatric patients and is not necessary to diagnose septic shock. Infants and children

with sepsis often maintain blood pressure despite the presence of septic shock through an increase in heart rate, systemic vascular resistance, and venous

tone but have a limited capacity to augment myocardial stroke volume. As a result, infants and children are also more likely to exhibit cold shock in sepsis

compared to the classic presentation of warm (or hyperdynamic or vasodilated) shock in adults. (See "Systemic inflammatory response syndrome (SIRS)

and sepsis in children: Definitions, epidemiology, clinical manifestations, and diagnosis", section on 'Shock'.)

Signs of infection Patients should be simultaneously evaluated for an infectious source to distinguish non-infectious from septic shock. Fever, cough or

congestion, dyspnea, hypoxemia, rash, abdominal pain, myalgias, immunocompromising condition (eg, chemotherapy, sickle cell disease, or other known

conditions associated with splenic dysfunction or primary immune deficiency), leukocytosis, or leukopenia with thrombocytopenia should raise suspicion for

infection (table 2). Other factors concerning for specific infections, such as dysuria (urinary tract infection), hematochezia (gastroenteritis), headache and

neck stiffness (meningitis), bone or joint inflammation (Staphylococcus aureus), conjunctival suffusion/injection (toxic shock syndrome), ecthyma

(Pseudomonas species) and petechiae/purpura (meningococcemia), should also be quickly ascertained. (See "Systemic inflammatory response syndrome

(SIRS) and sepsis in children: Definitions, epidemiology, clinical manifestations, and diagnosis", section on 'Infection'.)

If an infection is suspected or a non-infectious etiology of shock is not clear, current guidelines recommend obtaining blood, urine, and, as indicated, other

cultures and administering empiric broad-spectrum antibiotics within one hour of presentation [10]. Antibiotic therapy should not be delayed beyond one hour

in order to obtain cultures if there is a concern for severe sepsis or septic shock. Patients with a recent history of an immunocompromising condition (eg,

neutropenia, chemotherapy, sickle cell disease, or primary immune deficiency) are at highest risk for sepsis and severe complications and their outcome is

highly dependent on rapid antimicrobial treatment. (See 'Initial antimicrobial therapy' below.)

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Suggestive laboratory findings Suggested laboratory studies for children with sepsis and septic shock are discussed in detail separately and include

(see "Systemic inflammatory response syndrome (SIRS) and sepsis in children: Definitions, epidemiology, clinical manifestations, and diagnosis", section on

'Laboratory studies'):

Rapid blood glucose

Arterial or venous blood gas

Complete blood count with differential

Blood lactate

Serum electrolytes

Blood urea nitrogen and serum creatinine

Ionized blood calcium

Serum total bilirubin and alanine aminotransferaseProthrombin and partial thromboplastin times (PT and PTT)

International normalized ratio (INR)

Fibrinogen and D-dimer

Blood culture

Urinalysis

Urine culture

Other cultures as indicated by clinical findings

Diagnostic serologic testing as indicated to identify suspected sources of infection

Inflammatory biomarkers (eg, C-reactive protein, procalcitonin) in selected cases

The following laboratory findings support the diagnosis of septic shock:

Lactic acidosis indicated by metabolic acidosis on blood gases and elevation of arterial blood lactate (>3.5 mmol/L) (see "Systemic inflammatory

response syndrome (SIRS) and sepsis in children: Definitions, epidemiology, clinical manifestations, and diagnosis", section on 'Laboratory studies' )

Age-specific leukocytosis or leukopenia (table 1)

Platelet count 2 times upper limit of normal for

age

Pyuria indicating an urinary tract infection

PHYSIOLOGIC INDICATORS AND TARGET GOALS Restoration of tissue perfusion, such as reversal of shock, should be targeted to the following

therapeutic endpoints (goals in parentheses) (algorithm 1) [8-10]:

Quality of central and peripheral pulses (strong, distal pulses equal to central pulses)

Skin perfusion (warm, with capillary refill


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therapy. Limited observational evidence suggests that capillary refill time may correlate with ScvO2. (See "Initial management of shock in children", section

on 'Physiologic indicators and target goals'.)

RESUSCITATION

Early goal-directed therapy Goal-directed therapy for septic shock refers to an aggressive systematic approach to resuscitation targeted to

improvements in physiologic indicators of perfusion and vital organ function within the first six hours. Effective treatment of septic shock requires rapid

correction of circulatory dysfunction with continuous monitoring and re-evaluation at frequent intervals and early administration of empiric broad-spectrum

antimicrobial therapy [10].

We suggest that children with septic shock receive treatment according to the 2007 American College of Critical Care Medicine (ACCM) guidelines with

emphasis on early goal-directed therapy (algorithm 1) [8]. These guidelines are also largely compatible with the algorithm for pediatric septic shock promoted

in the Pediatric Advanced Life Support (PALS) course (algorithm 2). However, the ACCM guidelines provide a tighter time frame for optimal delivery of initial

intravenous fluid boluses. The timing of therapeutic actions in the ACCM guidelines should be viewed as best practices for resuscitation of a child with septic

shock. However, meeting the time targets may not always be possible within the first hour of illness depending upon patient factors and available pediatric

expertise.

This recommendation is supported by one trial and observational studies that show a marked reduction in mortality among children with severe sepsis after

wide dissemination of the 2002 ACCM guidelines on which the 2007 guidelines are based as follows:

In a trial of goal-directed therapy in 102 children with severe sepsis or fluid-refractory septic shock treated in two pediatric intensive care units, 28-day

mortality was lower in patients who received goal-directed therapy versus therapy guided by blood pressure (12 versus 39 percent, respectively)

primarily due to the marked benefit of goal-directed therapy among the children with central venous oxygen saturation (ScvO2) 70 who received goal-directed therapy also had lower mortality than controls (12 versus 22

percent), this difference was not statistically significant.

Institution of timely goal directed interventions by a mobile intensive care team compatible with the ACCM 2002 guidelines, including early andaggressive bolus colloid administration, endotracheal intubation and mechanical ventilation, and vasoactive therapy in conjunction with regionalization

of care for 331 children with meningococcemia in the United Kingdom was associated with a decrease in the case fatality rate from 23 to 2 percent

over five years (annual reduction in the odds of death 0.41, 95% CI: 0.27-0.62) [18].

Analysis of the case fatality rate among children treated for sepsis and purpura (primarily caused by Neisseria meningitidis, serogroup C) over 20

years in a childrens hospital demonstrated a drop in annual mortality from approximately 20 to 1 percent with no deaths after 2002, corresponding to

release of the ACCM guidelines and a nation-wide meningococcal C vaccination campaign [19].

In the United States, the annual death rate from severe sepsis was estimated as 4 percent (2 percent in healthy children and 8 percent in children with

prior chronic illness) in 2003 compared with 9 percent in 1999 [ 2,3].

Airway and breathing All patients with septic shock should initially receive 100 percent supplemental oxygen to optimize blood oxygen content and,

thus, oxygen delivery to tissues. Oxygenation should be monitored using continuous pulse oximetry (SpO2). Once adequate perfusion has been restored,

supplemental oxygen should be titrated to avoid SpO2 >97 percent to prevent the adverse effects (eg, lung injury and microcirculatory vasoconstriction)

associated with hyperoxia and free radical generation [20]. (See "Continuous oxygen delivery systems for infants, children, and adults" and "Basic airwaymanagement in children".)

Endotracheal intubation using rapid sequence intubation (RSI) is frequently necessary in children with septic shock to protect the airway, assist with

ventilation, and/or promote oxygenation. In addition, endotracheal intubation and sedation reduces the work of breathing which may avoid diversion of cardiac

output to the muscles of respiration and may improve perfusion to other organs. A rapid overview of RSI in children is provided in the table ( table 4). Emergent

endotracheal intubation in children and pediatric rapid sequence intubation (RSI) are discussed in detail separately. (See "Emergent endotracheal intubation

in children" and "Rapid sequence intubation (RSI) in children".)

Key actions when performing RSI in children with septic shock include:

Patients with hemodynamic instability should receive appropriate support with fluid and/or catecholamines (see below) prior to or during intubation.

Ketamine, if available and not contraindicated, is preferable for sedation prior to endotracheal intubation. (See "Sedation or induction agents for rapid

sequence intubation in adults", section on 'Ketamine'.)

Etomidate inhibits cortisol formation and should not be used routinely. If etomidate is used, we suggest the following:

It is important to evaluate for signs of adrenal insufficiency sometimes evidenced by refractory shock [ 21,22]. (See "Rapid sequence intubation

(RSI) in children", section on 'Etomidate' and "Septic shock: Ongoing management after resuscitation in children", section on 'Address adrenal

insufficiency'.)

Emergency clinicians should inform the physicians assuming care for the patient in the intensive care unit when etomidate has been used for

induction.

Etomidate should not be used as an infusion or in repeated bolus doses for maintenance of sedation after intubation.

Thiopental and propofol are associated with hypotension and should be avoided in children with septic shock.

When performing rapid sequence intubation in a child with septic shock, it is important to choose agents that do not worsen cardiovascular status.

Previously, etomidate was a common choice because it typically does not compromise hemodynamic stability. However, small observational studies in

children with sepsis and septic shock undergoing intubation with or without etomidate indicate that one dose of etomidate is associated with lower levels of

serum cortisol, cortisol to 11-deoxycortisol ratios, and higher adrenocortical hormone levels for up to 24 hours [21,23]. In one case series of 31 children withmeningococcal sepsis who required endotracheal intubation, of the eight children who died, seven received etomidate [23].

The 2007 update to the Clinical Guidelines for Hemodynamic Support of Neonates and Children with Septic Shock from the American College of Critical Care

Medicine states that etomidate is no longer recommended to sedate children with septic shock [8]. The 2010 advanced life support recommendations

provided by the American Heart Association and the International Liaison Committee on Resuscitation on which the Pediatric Advanced Life Support course

is based also suggest that etomidate not be used routinely in children with septic shock [9].


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Treat hypoglycemia and hypocalcemia Children with septic shock are at risk for hypoglycemia and hypocalcemia Rapid blood glucose and ionized

calcium should be measured as intravenous access is obtained.

Hypoglycemia Hypoglycemia should be corrected by rapid intravenous infusion of dextrose as described in the rapid overview ( table 5). After initial

hypoglycemia is reversed, the clinician should provide a continuous infusion of dextrose to maintain blood glucose in a safe range (70 to 150 mg/dL

[3.89 to 8.33 mmol/L]) for children whose condition does not permit oral intake. Hypoglycemia may also be an indicator of adrenal insufficiency in

predisposed children and those with refractory septic shock. (See 'Corticosteroids' below and "Septic shock: Ongoing management after resuscitation

in children", section on 'Address adrenal insufficiency'.)

In normoglycemic young children, a continuous maintenance infusion of dextrose 10 percent is a reasonable option to prevent the occurrence of

hypoglycemia and is suggested by the American College of Critical Care Medicine [8]. Hyperglycemia should be avoided.

Hypocalcemia Children with persistent shock in association with an ionized calcium 60 mL/kg of crystalloid fluid, have hypoalbuminemia (albumin 15 mL/kg and should be avoided. (See "Treatment of hypovolemia (dehydration) in

children", section on 'Crystalloid versus colloid' and "Evaluation and management of severe sepsis and septic shock in adults", section on 'Intravenous

fluids'.)

Preliminary evidence in one small pediatric trial suggests that administration of hypertonic saline may achieve hemodynamic stability with a lower

volume of fluid, but its impact on other outcomes relative to normal saline are uncertain [31]; thus, we do not advocate use of hypertonic saline outside

of an experimental protocol.

Resource-limited settings In resource-limited settings, fluid resuscitation according to emergency triage assessment and treatment guidelines

developed by the World Health organization is suggested for children with signs of shock. (See "Initial management of shock in children", section on

'Resource limited settings'.)

In resource-limited settings that cannot provide advanced airway and circulatory support, children with signs of shock and severe febrile illness but without

dehydration or hemorrhage who receive rapid bolus administration of albumin or normal saline may have increased mortality. Thus, rapid fluid infusion

according to the American College of Critical Care Medicine as described above should be avoided in this special population of patients. (See "Initial

management of shock in children", section on 'Risks'.)

Initial antimicrobial therapy Intravenous antimicrobial therapy should be initiated immediately after obtaining appropriate cultures with the goal of

completing administration within one hour of presentation. Each hour delay in antibiotic administration has been associated with an approximately 8 percent


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increase in mortality [32]. In patients in septic shock, effective delivery of antimicrobials usually requires two ports or sites for intravenous access: one

devoted to fluid resuscitation and one for antimicrobial delivery. Antimicrobials should not be withheld for children in whom lumbar puncture cannot be

performed safely due to hemodynamic instability or coagulopathy (algorithm 3).

The choice of antimicrobials can be complex and should consider the child's age, history, comorbidities, clinical syndrome, Gram stain data, and local

resistance patterns. Consultation with an expert in pediatric infectious disease is strongly encouraged for all children with septic shock.

General principles for initial antimicrobial coverage for children who are critically ill with sepsis include the following:

All children with septic shock should receive coverage for methicillin-resistant Staphylococcus aureus (MRSA).

Coverage for enteric organisms should be added whenever clinical features suggest genitourinary (GU) and/or gastrointestinal (GI) sources (eg,

perforated appendicitis or bacterial overgrowth in a child with short gut syndrome).

Treatment for Pseudomonas species should be included for children who are immunosuppressed or at risk for infection with these organisms (ie, those

with cystic fibrosis).

Listeria monocytogenes and herpes simplex virus are important pathogens in infants 28 days of age.

When treating empirically, antibiotics which can be given by rapid intravenous bolus (eg, beta-lactam agents or cephalosporins) should be

administered first followed by infusions of antibiotics, such as vancomycin, that must be delivered more slowly.

Ongoing antimicrobial therapy should be modified based upon culture results, including antimicrobial susceptibility and the patients clinical course.

Suggested initial empiric antimicrobial regimens based upon patient age, level of immunocompetence, and previous antibiotic administration include:

Children >28 days of age who are normal hosts:

Vancomycin (15 mg/kg, maximum 1 to 2 g, for the initial dose)PLUS cefotaxime (100 mg/kg, maximum 2 g, for the initial dose) OR ceftriaxone (75 mg/kg, maximum 2 g, for the initial dose)

Consider adding an aminoglycoside (eg, gentamicin) for possible GU source and/orpiperacillin with tazobactam, clindamycin ormetronidazole for

possible GI source

Children >28 days who are immunosuppressed or at risk for infection with Pseudomonas species:

Vancomycin (15 mg/kg, maximum 1 to 2 g, for the initial dose)

PLUS cefepime (50 mg/kg, maximum 2 g, for the initial dose) OR ceftazidime (50 mg/kg, maximum 2 g, for the initial dose)

PLUS an aminoglycoside (eg, gentamicin, amikacin) or carbapenem (eg, imipenem, meropenem) in settings where bacterial organisms with

extended-spectrum beta-lactamase (ESBL) resistance are prevalent. For patients who have been recently (within two weeks) treated broad-

spectrum antibiotics (eg, third-generation cephalosporin, aminoglycoside, or fluoroquinolone), the addition of a carbapenem is favored over an

aminoglycoside.

Children who cannot receive penicillin or who have recently received broad-spectrum antibiotics:

Vancomycin (age appropriate dose)

PLUS Meropenem (


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Cold shock The American College of Critical Care Medicine (ACCM) guidelines suggest that patients with cold shock (eg, poor perfusion, cold

extremities) that do not respond to initial boluses of 40 to 60 mL/kg of fluid receive dopamine infusions (starting dose 5 mcg/kg per minute, titrate to response

up to 10 mcg/kg per minute) (algorithm 1)[8]. At lower doses, dopamine improves splanchnic and renal blood flow and, at higher doses, it provides both

inotropic and vasopressor support. Unlike adults, dopamine is still a first-line agent in children because of its wide availability and practitioner familiarity, and

no evidence has correlated dopamine use with increased mortality in children with septic shock. However, infants younger than one year of age may be less

responsive to dopamine [8].

Of note, in the Pediatric Advanced Life Support guidelines, low-dose dopamine is suggested for patients with septic shock but normal blood pressures and

epinephrine is suggested for patients with cold shock (algorithm 2) [9]. No trials have directly compared dopamine to epinephrine for the treatment of cold

shock in children. Thus, the optimal approach is debated and awaits further study.

If cold shock is resistant to dopamine infusion at a dose of 10 mcg/kg per minute, epinephrine infusion at a rate between 0.05 to 0.3 mcg/kg per minute may

be added [8]. At doses exceeding 0.1 mcg/kg/minute (and possibly lower in some patients), alpha-adrenergic effects of epinephrine are more pronounced and

systemic vasoconstriction may be more evident. Examples of how to prepare an epinephrine infusion for a 10 kg or 20 kg child are provided in the tables

(table 7 and table 8).

Warm shock For patients with warm shock (eg, bounding pulses, pink extremities, and flash capillary refill) the American College of Critical Care

Medicine and Pediatric Advanced Life Support guidelines suggest norepinephrine infusion starting at 0.03 to 0.05 mcg/kg/minute as the first-line drug

(algorithm 1 and algorithm 2) [8]. If dopamine infusion has already been started then norepinephrine can be added to dopamine.

Corticosteroids Patients who persist with shock in spite of rapid fluid administration and continuous infusions of epinephrine or norepinephrine may have

adrenal insufficiency. Risk factors include purpura fulminans, recent or chronic treatment with corticosteroids, hypothalamic or pituitary abnormalities, or

adrenal insufficiency (congenital or acquired). When adrenal insufficiency is suspected, administration ofhydrocortisone in stress doses (50mg/m2/day or 2

mg/kg per day, intermittent or continuous infusion, maximum dose 50 mg/kg per day) is suggested [8]. Although evidence is lacking regarding the best

method to identify adrenal insufficiency in children with refractory septic shock, assessment of adrenal status (either baseline serum cortisol or

adrenocorticotropin hormone stimulation testing) is advised prior to corticosteroid administration. (See "Septic shock: Ongoing management after

resuscitation in children", section on 'Address adrenal insufficiency'.)

Transfer to definitive care After resuscitation, children with septic shock should be managed by clinicians with pediatric critical care expertise in a

setting that has the necessary resources to provide pediatric intensive care. Children with septic shock who present to facilities without the necessary clinical

expertise or resources should undergo timely transfer to an appropriate facility. Use of a pediatric specialized team is associated with improved patient

survival and fewer adverse effects during transport. Thus, the use of pediatric specialized teams for transport of children with septic shock is recommended

whenever it is available. (See "Prehospital pediatrics and emergency medical services (EMS)", section on 'Inter-facility transport'.)

SUMMARY AND RECOMMENDATIONS

A clinical diagnosis of septic shock is made in children who have signs of inadequate tissue perfusion, two or more criteria for the systemic

inflammatory response syndrome (table 1), and suspected or proven infection. (See 'Rapid recognition' above and "Systemic inflammatory response

syndrome (SIRS) and sepsis in children: Definitions, epidemiology, clinical manifestations, and diagnosis", section on 'Diagnosis'.)

All patients with septic shock should initially receive 100 percent supplemental oxygen to optimize blood oxygen content and, thus, oxygen delivery to

tissues. Once adequate perfusion has been restored, supplemental oxygen should be titrated to avoid oxygen saturation by pulse oximetry of greater

than 97 percent to prevent the adverse effects associated with hyperoxia and free radical generation (eg, lung injury and microcirculatoryvasoconstriction). (See 'Airway and breathing' above.)

Endotracheal intubation using rapid sequence intubation (RSI) is frequently necessary in children with septic shock to protect the airway, assist with

ventilation, and/or promote oxygenation. When performing RSI in children with septic shock, ketamine, if available and not contraindicated, is

preferable for sedation prior to endotracheal intubation. Etomidate should not be used routinely in patients with septic shock. A rapid overview of RSI in

children is provided in the table (table 4). (See 'Airway and breathing' above.)

We suggest that children with septic shock receive treatment according to the American College of Critical Care Medicine (ACCM) guidelines including

goal-directed therapy which provides a systematic approach to resuscitation of septic shock targeted to specific improvements in physiologic

indicators of perfusion and vital organ function (algorithm 1) (Grade 2C). For children in resource-rich settings, rapid infusion of isotonic fluid (eg,

normal saline) and early administration of empiric broad-spectrum antimicrobial therapy are essential actions. (See 'Early goal-directed therapy' above

and 'Physiologic indicators and target goals' above and 'Resuscitation' above.)

The American College of Critical Care Medicine guidelines suggest the initiation of vasoactive therapy in children with septic shock who have not

improved after 40 to 60 mL/kg of isotonic crystalloid along with continued fluid administration. Specific vasopressor agents (eg, dopamine, epinephrine,

or norepinephrine) are given based upon whether the patient has clinical findings of cold or warm shock. (See 'Fluid-refractory shock' above.)

Patients who persist with shock in spite of rapid fluid administration and continuous infusions of epinephrine or norepinephrine may have adrenal

insufficiency. When adrenal insufficiency is suspected, administration ofhydrocortisone in stress doses (50 to 100 mg/m2/day or 1 to 2 mg/kg per

day, intermittent or continuous infusion, maximum dose 50 mg/kg per day) is suggested [8]. Assessment of adrenal status (either baseline serum

cortisol or adrenocorticotropin hormone stimulation testing) is advised prior to corticosteroid administration. (See 'Corticosteroids' above.)

After initial resuscitation, ongoing aggressive management of septic shock should continue according to the principles of goal-directed therapy for

children in whom adequate circulation has not been restored (algorithm 1). This care should be provided by clinicians with pediatric critical care

expertise in a setting that has the necessary resources to provide pediatric intensive care. (See 'Transfer to definitive care' above and "Septic shock:

Ongoing management after resuscitation in children".)

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GRAPHICS

Pediatric systemic inflammatory response syndrome criteria

Age group

Heart rate (beats/min)Respiratory

rate(breaths/min)

Leukocytecount

(leukocytes x

103/mm3)

Systolic blood

pressure(mmHg)Tachycardia Bradycardia

Newborn (0 days to1 wk)

>180 50 >34 180 40 >19.5 or 17.5 or 140 NA >22 >15.5 or 130 NA >18 >13.5 or 14 >11 or


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Evaluation of common sources of sepsis

Suspected site Symptoms/signs Microbiologic evaluation

Upper respiratory tract Pharyngeal inflammation plus exudate swelling and lymphade nopathy

Throat swab for aerobic culture

Lower respiratory tract Productive cough, pleuritic chest pain,consolidative auscultatory findings

Sputum of good quality, rapid influenz atesting, urinary antigen testing (eg,pneumococcus, legione lla), quantitativeculture of protected b rush orbronchoalveolar lavage

Urinary tract Fever, urgency, dysuria, loin pain Urine microscopy showing pyuria

Vascular catheters: arterial, centralvenous

Redness or drainage at insertion site Culture of blood (from the catheter and aperiphe ral site), culture cathe ter tip (ifremoved)

Indw elling ple ura l ca the te r Re dne ss or dra ina ge at ins ertion site Culture of ple ura l fluid (through ca the te r),culture of cathete r tip (if removed)

Wound or burn Inflammation, edema, erythema,discharge of pus

Gram stain and culture of draining pus,wound culture not reliable

Skin/soft tissue Erythema, edema, lymphangitis Culture blister fluid or draining pus; roleof tissue aspirates not proven

Central nervous system Signs of meningeal irritation CSF microscopy, protein, glucose, culture,bacterial antigen tes t

Gastrointestinal Abdominal pain, distension, diarrhea, andvomiting

Stool culture for Salmonella, Shigella, andCampylobacter

Intraabdominal Specific abdominal symptoms/signs Aerobic and anaerobic culture of percutaneously or surgically drainedabdominal fluid collections

Peritoneal d ia lys is (PD) ca thete r C loudy PD flu id , abdominal pain , feve r Cell coun t and cu ltu re of PD flu id

Genital tractWomen: Low abdominal pain, vaginaldischarge

Men: Dysuria, frequency, urgency, urgeincontinence, cloudy urine, prostatictenderness

Women: Endocervical and high vaginalswa bs onto selective media

Men: Urine Gram stain and culture

Joint Pain, warmth, decreased range of motion Arthrocentesis w ith cell counts, Gramstain, and culture

CSF: cerebrospinal fluid; PD: peritonea l dialysis.

Adapted from: Cohen J, Microbiologic requirements for studies of sepsis . In: Sibbald WJ, Vincent JL (eds), Clinical Trials for the Treatment ofSepsis, Springer-Verlag, Berlin, 1995, p.73.




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Recommendations for stepwise management of hemodynamic support in

infants and children with sepsis

Algorithm for time sensitive, goal-directed stepwise management of hemodynamicsupport in infants and children. Proceed to next step if shock persists. (1) First hour

goalsRestore and maintain heart rate thresholds, capillary refill 2 sec, and normalblood pressure in the first hour/emergency department. Support oxygenation andventilation as appropriate. (2) Subsequent intensive care unit goalsIf shock is notreversed, intervene to restore and maintain normal perfusion pressure (mean arterialpressure [MAP]-central venous pressure [CVP]) for age, central venous O2 saturation

>70 percent, and CI >3.3,


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Pediatric respiratory rate and heart rate by age*

Age groupRespiratory rate Heart rate

Median (1st-99th percentile) Median (1st-99th percentile)

0-3 months 43 (25-66) 143 (107-181); term newborn at birth: 127 (90-164)

3-6 months 41 (24-64) 140 (104-175)

6-9 months 39 (23-61) 134 (98-168)

9-12 months 37 (22-58) 128 (93-161)

12-18 months 35 (21-53) 123 (88-156)

18-24 months 31 (19-46) 116 (82-149)

2-3 years 28 (18-38) 110 (76-142)

3-4 years 25 (17-33) 104 (70-136)

4-6 years 23 (17-29) 98 (65-131)

6-8 years 21 (16-27) 91 (59-123)

8-12 years 19 (14-25) 84 (52-115)

12-15 years 18 (12-23) 78 (47-108)

15-18 years 16 (11-22) 73 (43-104)

* The respiratory and he art rates p rovided are ba sed upon measurements in awa ke, healthy infants and children at rest. Many clinicalfindings be sides the actual vital sign measurement must be taken into account when determining whe ther a specific vital sign is normalin an individua l patient. Values for hea rt rate or respiratory rate tha t fall within normal limits for age may still represen t abno rmalfindings that are caused by underlying disease in a particular infant or child.Data from: Fleming S, Thompson M, Stevens R, et al. Normal ranges of heart rate and respiratory rate in children from birth to 18 years ofage: a systematic review of observational studies. Lancet 2011; 377:1011.


http://www.uptodate.com/contents/septic-shock-rapid-recognition-and-initial-resuscitation-in-children?topicKey=EM%2F85767&elapsedTimeMs=0&source=see_link&view=print&displayedView=full11 / 19


12/19

Pediatric Advance Lifes Support septic shock algorithm

* NOTE: Fluid refractory and dopamine- or norepinephrine-dependent shock defines patientat risk for adrenal insufficiency. Draw bas eline cortisol; cons ider ACTH stimulation te st ifunsure of need for steroids. If adrenal insufficiency is suspected give hydrocortisone 2mg/kg bolus IV; maximum 100 mg.Reprinted with permission from: American Academy of Pediatrics, American Heart As sociation.

Management of Shock. In: Pediatric Advanced Life Support Provider Manual, Chameides L,Samson RA, Schexnayder S, Hazinski MF (Eds), American Heart Association, 2011 . Copyright 2011 American Heart Association.




13/19

Rapid overview of rapid sequence intubation in children

Preoxygenation

Begin preoxygenation as soon a s the d ecision to intubate is considered.

Administer oxygen at the highest concentration available.

Preparation

Identify conditions that w ill affect choice of medications.

Identify conditions that w ill predict difficult intubation o r bag-mask ventilation.

Assemble equipment and check for function.

Develop contingency plan for failed intubation.

Pretreatment

Atropine: All children 1 yea r, children


14/19

Rapid overview for hypoglycemia in adolescents and children, other than neonates

Clinical features

Any patient with acute lethargy or coma should have an immediate measurement of blood glucose to determine if hypoglycemia isa poss ible cause

Other findings of hypoglycemia are nonspecific* and vary by age:

Infants

- Irritability

- Lethargy

- Jitteriness

- Feeding problems

- Hypothermia

- Hypotonia

- Tachypne a

- Cyanosis

- Apnea

- Seizures

Older children and adolescents

- Autonomic response (tends to occur with blood glucose


15/19

Establish vascular access as soon as possible

After initial hypoglycemia is reversed, provide add itional glucose and treatment ba sed upon s uspected etiology:

- Give children and adolescents with type I diabetes mellitus a normal diet

- Give pa tients with an unknown cause of hypoglycemia intravenous infusion of dextrose 10 percent (6 to 9 mg/kg per

minute) titrated to maintain blood glucose in a s afe and appropriate range (70 to 150 mg/dL [3.89 to 8.33 mmol/L])

- Give patients, who have ingested a sulfonylurea and have recurrent hypoglycemia, octreotide (dose: 1 to 1.5 mcg/kg IMor SQ, maximum dose 150 mcg every 6 hou rs) in addition to glucose. (Refer to UpToDate topic on sulfonylurea poisoning).

Measure a rapid blood and plasma glucose 15 to 30 minutes a fter the initial IV glucose bolus and then monitor every 30 to 60minutes until stable (minimum of four hours) to ensure tha t plasma glucose concentration is maintained in the normal range(>70 to 100 mg/dL [>3.89 to 5.55 mmol/L])

Obtain pediatric endocrinology consultation for patients with hypoglycemia of unknown cause

Obtain medical toxicology consultation for patients with ingestion of oral hypoglycemic agents by calling the United States

Poison C ontrol Network at 1-800-222-1222 or access the World Health Organizations list of international poison centers(www.who.int/gho/phe/chemical_safety/poisons_centres/en/index.html)

Admit the following patients:

- Cannot maintain normoglycemia with oral intake

- Hypoglycemia of unknown cause

- Ingestion of long-acting hypoglycemic age nts

- Recurrent hypoglycemia during the period of observation

IV: intravenous; IM: intramuscular; SQ: subcutaneous; D10W: 10 percent dextrose in water; D25W: 25 percent dextrose in water;D50W: 50 percent dextrose in wate r.

* These findings may also occur in infants with sepsis, congenital heart disease, respiratory distress syndrome, intraventricularhemorrhage, other metabolic disorders, and in children and adolescents with a variety of underlying conditions. Specific labora tory studies to obta in in children include b lood sa mples for glucose, insulin, C-pep tide, beta -hydroxybutyrate, lactate(free flowing blood must be obtained without a tourniquet), plasma acylcarnitines, free fatty acids, growth hormone, and cortisol. Higher doses of glucose (eg, 0.5 to 1 g/kg [5 to 10 mL/kg of 10 percent dextrose in water OR 2 to 4 mL/kg of 25 percent dextrose inwater]) may be needed to correct hypoglycemia caused by sulfonylurea ingestion. (For more detail, refer to UpToDate topic onsulfonylurea agent poisoning). Glucagon will reverse hypoglycemia cause d by e xcess endoge nous o r exogenous insulin and w ill not be effective in pa tients withinadequate glycogen stores (prolonged fasting), ketotic hypoglycemia, or are unable to mobilize glycogen (glycogen s torage disease s).

Of note, children may exhaust their glycogen stores in as little as 12 hours. Other conditions in which glycogen cannot be effectivelymobilized include e thano l intoxication in children, adrenal insufficiency, and certain inborn errors o f metabolism (eg, a d isorder ofglycogen synthesis and glycogen storage disea ses).




16/19

Management algorithm for infants (1 month) and children

with suspected bacterial meningitis

STAT: intervention s hould be performed emergently; CBC: complete blood count;

PT: prothrombin time; PTT: partial thromboplas tin time; BUN: blood ureanitrogen; CSF: cerebrospinal fluid.* Antimicrobial therapy should not be delayed if lumbar puncture cannot beperformed or is unsuccessful. Decisions regarding the administration of dexamethasone should beindividualized de pending on careful analysis of the risks a nd be nefits a sdiscussed in the te xt. (See "Treatment and prognosis of acute b acterialmeningitis in children").

Empiric antibiotic therapy and dexamethasone (if warranted) should beadministered immediately after cerebrospinal fluid is obtained; if dexamethasoneis to be a dministe red, it should be given before , or immediately after, the firstdose of antimicrobial therapy.

Adapted from:1. Tunkel AR, Hartman BJ, Kaplan SL, et al. Practice guidelines for the

management of bacterial meningitis. Clin Infect Dis 2004; 39:12672. Fleisher GR. Infectious disease emergencies. In: Textbook of Pediatric

Emergency Medicine, 5th ed, Fleisher GR, Ludwig S, Henretig FM (Eds),

Lippincott Williams & Wilkins, Philadelphia 2006. p.792.




17/19

Cerebrospinal fluid (CSF) patterns and diagnosis of viral meningitis in children

PathogenWBC

(cells/mm3)RBC

Glucose(mg/dL)

Protein(mg/dL)

Viral diagnosis

Enterovirus 100-1000 None NL/SL


18/19

Example of epinephrine infusion - pediatric 10 kg

Example of preparation of epinephrine infusion for refractory symptoms of anaphylaxis for pediatricpatient of 10 kg body weight for emergency/critical care units

Epinephrine 10 micrograms/mL (0.01 mg/mL)

Add 1 mg (1000 micrograms) of epinephrine to 100 mL of 5 percent dextrose water (D5W).Resulting concentration is 10 micrograms per milliliter (mL).

Preparation

1. CHECK vial strength.

2. To prepare epinephrine infusion for a final concentration of10 micrograms per mL, dilute 10 mL of0.1 mg/mL epinephrine (alsolabeled 1:10,000) in 100mL of D5W OR1 mL of 1 mg/mL ep inephrine (also labeled 1:1000) in 100 mL of D5W.*

Administration

Infuse an initial dose of 0.1 micrograms per kg per minute using a programmable infusion pump and titrate as needed whilecontinuously monitoring the patient's cardiac rhythm and blood pressure.

Pediatric dose for 10 kg child

Administration rate

1 milligram epinephrine diluted in 100 mL D5W

10 micrograms per milliliter

Micrograms per kgper minute

Multiply by patientweight (10 kg)

Micrograms perminute

mL per minute for10 kg child

Multiply by 60minutes

mL per hour for 10kg child

0.05 0.5 0.05 3

0.1 1 0.1 6

0.2 2 0.2 12

0.3 3 0.3 18

0.4 4 0.4 24

0.5 5 0.5 30

0.6 6 0.6 36

0.7 7 0.7 42

0.8 8 0.8 48

0.9 9 0.9 54

1 10 1 60

To reduce the risk of making a medication error, we sugges t that centers have a vailable a n institutionally approved protocolfor epinephrine infusion that includes steps on how to prepa re and administer the infusion and standard concentration(s)

The above ta ble is provided a s an example; there are othe r acceptable concentrations

Intravenous epinephrine, like all vasopressors, can cause life-threatening hypertension, cardiac ischemia, and

ventricular arrhythmias. It should be administered ONLY by clinicians trained and experienced in dose titration ofintravenous epinephrine using continuous non-invasive electronic monitoring of heart rate and blood pressure.

Epinephrine is an ischemia causing agent and peripheral venous irritant. Monitor infusion site for extravasation. See Lexicompdrug refe rence for information on mana ging extravasation including infiltration of phentolamine. Cen tral line administration ispreferred when available.

* Unused diluted so lutions should be d iscarded within 24 hours or less of preparation depe nding on local standards.References: Gahart BL, Nazareno AR; Intravenous Medications 28th ed. Elsevier-Mosby 2012 St. Louis , MO; Lieberman P, et al. J AllergyClin Imm unol 2010; 126(3):477.




19/19

Example of epinephrine infusion - pediatric 20 kg

Example of preparation of epinephrine infusion for refractory symptoms of anaphylaxis for pediatricpatient of 20 kg body weight for emergency/critical care units

Epinephrine 10 micrograms/mL (0.01 mg/mL)

Add 1 mg (1000 micrograms) of epinephrine to 100 mL of 5 percent dextrose water (D5W).Resulting concentration is 10 micrograms per milliliter (mL).

Preparation

1. CHECK vial strength.

2. To prepare epinephrine infusion for a final concentration of10 micrograms per mL, dilute 10 mL of0.1 mg/mL epinephrine (alsolabeled 1:10,000) in 100mL of D5W OR1 mL of 1 mg/mL ep inephrine (also labeled 1:1000) in 100 mL of D5W.*

Administration

Infuse an initial dose of 0.1 micrograms per kg per minute using a programmable infusion pump and titrate as needed whilecontinuously monitoring the patient's cardiac rhythm and blood pressure.

Pediatric dose for 20 kg child

Administration rate

1 milligram epinephrine diluted in 100 mL D5W

10 micrograms per milliliter

Micrograms per kgper minute

Multiply by patientweight (20 kg)

Micrograms perminute

mL per minute for10 kg child

Multiply by 60minutes

mL per hour for 10kg child

0.05 1 0.1 6

0.1 2 0.2 12

0.2 4 0.4 24

0.3 6 0.6 36

0.4 8 0.8 48

0.5 10 1 60

0.6 12 1.2 72

0.7 14 1.4 84

0.8 16 1.6 96

To reduce the risk of making a medication error, we sugges t that centers have a vailable a n institutionally approved protocolfor epinephrine infusion that includes steps on how to prepa re and administer the infusion and standard concentration(s)

The above ta ble is provided a s an example; there are othe r acceptable concentrationsIntravenous epinephrine, like all vasopressors, can cause life-threatening hypertension, cardiac ischemia, andventricular arrhythmias. It should be administered ONLY by clinicians trained and experienced in dose titration ofintravenous epinephrine using continuous non-invasive electronic monitoring of heart rate and blood pressure.

Epinephrine is an ischemia causing agent and peripheral venous irritant. Monitor infusion site for extravasation. See Lexicompdrug refe rence for information on mana ging extravasation including infiltration of phentolamine. Cen tral line administration ispreferred when available.

* Unused diluted so lutions should be d iscarded within 24 hours or less of preparation depe nding on local standards.References: Gahart BL, Nazareno AR; Intravenous Medications 28th ed. Elsevier-Mosby 2012 St. Louis , MO; Lieberman P, et al. J AllergyClin Imm unol 2010; 126(3):477.


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