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AuthorsScott L Weiss, MD

Wendy J Pomerantz, MD, MS

Section EditorsSusan B Torrey, MD

 Adrienne G Randolph, MD, MScSheldon L Kaplan, MD

Deputy Editor James F Wiley, II, MD, MPH

Septic shock: Ongoing management after resuscitation in children

Disclosures

 All topics are updated as new evidence becomes available and our peer review process is complete.Literature review current through: Apr 2013. | This topic last updated: Feb 15, 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 management of severe sepsis and septic shock in children after the first hour of resuscitation is reviewed here. The rapid recognition and initial

resuscitation of pediatric septic shock and the definitions, epidemiology, and clinical manifestations of sepsis in children are discussed separately. (See

"Septic shock: Rapid recognition and initial resuscitation in children" and "Systemic inflammatory response syndrome (SIRS) and sepsis in children:

Definitions, epidemiology, clinical manifestations, and diagnosis".)

RESUSCITATION — The key interventions in the initial resuscitation of children from septic shock are discussed in detail separately. (See "Septic shock:

Rapid recognition and initial resuscitation in children".)

OVERVIEW — Repeated, frequent assessment of the patient in septic shock is essential. In children who have responded to therapy with resolution of 

hypotension, ongoing monitoring, antimicrobial therapy, and optimal respiratory support are essential.

In patients with fluid-refractory hypotension, ongoing aggressive resuscitation should continue after the initial resuscitation of pediatric septic shock according

to the principles of goal-directed therapy, (algorithm 1). (See "Septic shock: Rapid recognition and initial resuscitation in children", section on 'Physiologic

indicators and target goals'.)

Whenever possible, children requiring resuscitation for septic shock should receive ongoing management by a pediatric critical care specialist or pediatrician

with similar expertise in a pediatric intensive care unit.

Priorities for continued management of children with septic shock include:

Control the infection by identifying the optimal choice of antimicrobial therapy based upon culture results and by ensuring that the source of infection is

controlled

Ongoing monitoring of respiratory status and provision of optimal respiratory support

Ongoing monitoring of tissue perfusion and blood pressure

Correction of electrolyte and metabolic derangements (eg, hypoglycemia, hypocalcemia)

In the subpopulation of children with fluid-refractory septic shock requiring continued vasopressor support, additional priorities include:

Placement of invasive monitoring devices (eg, central venous catheter, arterial line, bladder catheter) to accurately assess blood pressure and to

deliver vasopressor infusions safely

Continued fluid resuscitation and vasopressor delivery targeted to principles of goal-directed therapy

 Administration of blood products, when needed, to treat anemia and coagulopathy

Treatment of adrenal insufficiency and evaluation of other potential underlying causes (eg, hypothyroidism)

Provision of advanced therapies in patients who do not respond to conventional therapy

If physiologic goals have been achieved, indicating that perfusion is improved, the patient should continue to receive supportive treatment and careful

monitoring. The goals of treatment include achieving a normal blood pressure, improved mental status and good perfusion for the patient who is hypotensive.

For children with compensated shock and normal blood pressures, therapeutic endpoints based upon noninvasive indicators are reasonable targets, but may

be unreliable. (See "Septic shock: Rapid recognition and initial resuscitation in children", section on 'Physiologic indicators and target goals' .)

Eradicate infection — Prompt identification and treatment of the source of infection are essential to successful management of septic shock and constitute

critical interventions that can reverse septic shock. In contrast, other therapies (eg, fluid administration, vasoactive drug infusion, or mechanical ventilation)

are purely supportive in nature [8-10].

 A careful history and physical examination may yield clues to the source of sepsis and help guide subsequent microbiologic evaluation (table 1). Gram stain

of suspicious fluids may give early clues to the etiology of infection while cultures are incubating. In addition to cultures of specific sites, blood should be

drawn and inoculated into standard blood culture media. Blood cultures should be incubated both aerobically and anaerobically. (See "Blood cultures for the

detection of bacteremia".)

Eradication of the inciting infection is essential for the successful treatment of septic shock. This includes prompt administration of antimicrobial therapy and

source control. Initial antimicrobial therapy should provide broad spectrum coverage tailored to host factors, such as age and underlying medical conditions,

and be administered as soon as possible after presentation. (See "Septic shock: Rapid recognition and initial resuscitation in children", section on 'Initial

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antimicrobial therapy'.)

Source control (physical measures undertaken to eradicate a focus of infection, to eliminate ongoing microbial contamination, and to render a site

inhospitable to microbial growth and invasion) should be undertaken when possible because localized foci of infection (ie, abscess) may not respond to

antibiotics alone (table 1). As examples, potentially infected foreign bodies should be removed and abscesses, infected fluid collections, or tissues should be

percutaneously or surgically drained and débrided. (See "Necrotizing soft tissue infections", section on 'Treatment'.)

Continue respiratory support — Oxygenation should be monitored using continuous pulse oximetry (SpO2). Patients should continue to receive

supplemental oxygen to maintain oxygen saturation at 100 percent (patients with continued shock) or 97 percent (patients with restored perfusion and blood

pressure).

In patients with continued shock, endotracheal intubation should be performed if not already accomplished. Mechanical ventilation should be performed with

the following goals in mind [11,12]:

Keep plateau pressure ≤30 cmH2O

Keep tidal volume under 10 mL/kg ideal body weight. Tidal volume may need to be decreased as low as 4 to 6 ml/kg in patients with very low lung

compliance using lung protective ventilation strategies to achieve a plateau pressure ≤30 cmH2O [13,14]

Maintain arterial pH between 7.30 and 7.45

Titrate fraction of inspired oxygen (FiO2) and positive end-expiratory pressure to maintain arterial oxygen concentration (PaO2) between 60 and 80

mmHg (8 to 10.7 kPa) or pulse oximetry 90 to 97 percent in patients with hypoxia who require FiO2 ≥50 percent

Maintain hemoglobin ≥10 g/dL (see 'Blood transfusion' below)

Ongoing and invasive monitoring — During initial management, monitoring of tissue perfusion using physiologic indicators and target goals continues.

(See "Septic shock: Rapid recognition and initial resuscitation in children", section on 'Physiologic indicators and target goals' .)

In addition, the clinician should determine the need for invasive monitoring via intraarterial and central venous cannulas:

Intraarterial cannula placement – Although noninvasive blood pressure measurement is acceptable in patients who have markedly improved or had

total reversal of septic shock, automated blood pressures overestimate systolic blood pressure relative to intraarterial or Doppler ultrasound

measurements in hypotensive children and underestimate systolic blood pressure among hypertension patients [15]. Thus, insertion of an intraarterial

catheter is suggested if blood pressure is labile or if restoration of arterial perfusion pressures is expected to be a protracted process. However, efforts

to obtain intraarterial access should not interfere with the resuscitation of septic shock. Procedures for obtaining intraarterial access in children are

discussed separately. (See "Arterial puncture and cannulation in children", section on 'Arterial cannulation'.)

Central venous access – Central venous access is indicated in patients who require infusion of vasoactive drugs to maintain adequate tissue

perfusion, and in patients with catecholamine-resistant septic shock who warrant monitoring of central venous pressures (CVP) and central venous

oxygen saturation (ScvO2). In the absence of an elevated intraabdominal pressure, the correlation between femoral vein pressure and CVP is good,

though absolute values may differ slightly [16,17]. Changes in central venous oxygen saturation (ScvO2), which provides reliable information regarding

tissue oxygenation should also be frequently monitored [18]. If direct measure of ScvO2 is not available, limited evidence suggests that a capillary refill

time ≤2 seconds is associated with a ScvO2 ≥70 percent. However, capillary refill time can be brisk despite significant hemodynamic derangement inchildren with septic shock. (See "Initial management of shock in children", section on 'Physiologic indicators and target goals'.)

Continue fluid administration — The need for aggressive administration of fluids to optimize tissue perfusion and to achieve physiologic goals typically

continues beyond the first hour of care in children with septic shock. In patients with persistent poor perfusion or hypotension, boluses of fluids should

continue until the central venous pressure is 8 to 12 cmH2O (12 to15 cmH2O in mechanically ventilated patients) or evidence of cardiac insufficiency (eg,

pulmonary edema, enlarged heart) occurs. The volume per bolus and types of fluid are as for the resuscitation period (algorithm 1). Fluid input and output

should be carefully monitored on an hourly basis. (See "Septic shock: Rapid recognition and initial resuscitation in children", section on 'Intravenous fluid

therapy'.)

Fluid overload — Interstitial edema is common in sepsis due to increased vascular permeability. In patients with clinical findings of significant fluid

overload (eg, pitting edema, anasarca, or pulmonary edema), early initiation of diuretic therapy (eg, furosemide) may be appropriate in patients with hypoxia

and pulmonary edema after a period of 12 to 24 hours of sustained hemodynamic stability off vasoactive infusions. Patients in whom urine output remains

insufficient may warrant renal replacement therapy (eg, continuous veno-venous hemofiltration or intermittent hemodialysis). Observational studies in critically

ill children, including children with sepsis who received renal replacement therapies, indicate that more than 10 percent fluid overload is associated with

mortality [19,20]. However, the evidence is not sufficient to determine whether or not fluid overload has an independent deleterious effect on survival.

Nonsurvivors may have had more severe septic shock and therefore, required greater amount of fluid and were more likely to develop renal insufficiency.

Blood transfusion — Hemoglobin is the primary determinant of blood oxygen carrying capacity and, therefore, of tissue oxygen delivery. Thus, maintaining

adequate hemoglobin levels is a critical aspect of managing children with septic shock. We suggest a hemoglobin goal of 10 g/dL (equivalent to 30 percent

hematocrit) as a target to maintain with blood transfusion during resuscitation and ongoing management of children with septic shock ( algorithm 1) [12]. The

safety of tolerating a lower hemoglobin in unstable patients with vasopressor-dependent hypotension from sepsis has not been studied.

Once shock has resolved, a lower hematocrit threshold for blood transfusion is likely to be safe. As an example, in a multicenter unblinded trial of 137

stabilized children with sepsis (mean systemic arterial pressure was not below two standard deviations of normal for age and cardiovascular support was not

increased for at least two hours before enrollment) that compared restrictive transfusion (transfusion for hemoglobin <7.0 g/dL) with liberal transfusion

(transfusion for hemoglobin <9.5 g/dL), no clinically significant differences were found for the occurrence of new or progressive multiple organ dysfunction

syndrome (18.8 versus 19.1 percent), PICU length of stay (13 days in both groups), or PICU mortality (7 versus 3 percent, respectively) [ 21]. However, two

additional patients died in the restrictive transfusion group after discharge from the pediatric intensive care unit.

Given that a restrictive approach to transfusion in patients with sepsis does not appear inferior to more liberal management in stable patients recovering fromseptic shock, we typically use a hemoglobin of 7 g/dL as the threshold for blood transfusion in stable patients recovering from septic shock instead of 10

g/dL which we suggest for patients with ongoing hemodynamic instability.

Treat disseminated intravascular coagulation — Patients with septic shock frequently have disseminated intravascular coagulopathy that may warrant

treatment. Thus, baseline measures of clotting status should be routinely obtained in children with septic shock. (See "Septic shock: Rapid recognition and

initial resuscitation in children", section on 'Suggestive laboratory findings'.)

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There have been no trials to study the efficacy of platelet, fresh frozen plasma (FFP), or cryoprecipitate transfusions in children with sepsis and DIC.

Nevertheless, the use of these agents seems rational in patients with significant bleeding (melena, or prolonged bleeding from venipuncture sites) due to

thrombocytopenia and clotting factor consumption or significant risk of bleeding (eg, pre- or postoperative patients). (See "Disseminated intravascular 

coagulation in infants and children", section on 'Replacement therapy'.)

The goal of replacement therapy is to reduce or stop significant bleeding. Although replacement therapy should not be used to normalize laboratory tests

(which often is impossible), a reasonable guide for the judicious use of blood components in the setting of significant bleeding includes maintaining platelet

counts >50,000 per mm³ and fibrinogen concentration >100 mg/dL (1 mol/L). (See "Disseminated intravascular coagulation in infants and children", section on

'Replacement therapy'.).

Clotting factors can be replaced by either FFP or cryoprecipitate. FFP provides both procoagulant and anticoagulant proteins and is administered every 12 to

24 hours at a dose of 10 to 15 mL/kg per infusion. Cryoprecipitate has higher concentrations of factor VIII and fibrinogen, and can be used to correct

hypofibrinogenemia. It is administered every six hours as needed at a dose of 10 mL/kg per infusion. Platelet transfusions are administered with a goal of maintaining the platelet counts >50,000 per mm³. (See "Disseminated intravascular coagulation in infants and children", section on 'Replacement therapy'.)

 Although initial observational studies indicated that children with sepsis frequently have low circulating levels of activated protein C, administration of 

recombinant humanactivated protein C (drotrecogin alfa) has shown no benefit and may be harmful. As an example, in a multicenter randomized trial

comparing drotrecogin alpha with placebo for the treatment of children with severe sepsis, interim analysis demonstrated no benefit for treatment with

drotrecogin alpha and an increased incidence of central nervous system bleeding, particularly in those younger than 60 days [ 22]. As a result, this trial was

discontinued. A systematic review that included this trial concluded that recombinant human activated protein C should not be used for any children or for 

adults who are not severely ill [23]. In October 2011, drotrecogin alpha was voluntarily removed from the worldwide market by Eli Lilly due to a negative

second trial in adults with severe septic shock.

Observational and dose finding studies of protein C concentrate in selected children with severe meningococcal septic shock, and purpura fulminans have

shown potential promise. Protein C concentrate is not biologically active on administration (requires conversion to activated protein C by thrombin or 

thrombin bound to endothelial thrombomodulin) and is used mainly in patients with severe congenital protein C deficiency. (See "Treatment and prevention of 

meningococcal infection", section on 'Protein C concentrate' and "Protein C deficiency".)

Manage glucose abnormalities — Hypoglycemia remains a concern during the initial management phase of septic shock. Children have limited glycogen

stores and may develop profound hypoglycemia during periods of stress. Thus, blood glucose should be monitored frequently upon admission and at least

every six hours while the patient is unstable and corrected (table 2). (See "Septic shock: Rapid recognition and initial resuscitation in children", section on

'Treat hypoglycemia and hypocalcemia'.)

Once tissue perfusion is restored and shock is resolved, children should receive intravenous fluid that contains dextrose sufficient to maintain euglycemia.

This therapy typically consists of 5 to 10 percent dextrose in electrolyte solution appropriate to the patient’s ongoing sodium and potassium requirements.

The glucose dose is determined by age: 8 mg/kg per minute (neonates), 4 mg/kg per minute (children), 2 mg/kg per minute (adolescents) [24].

Hyperglycemia is commonly present in children with septic shock. Data regarding exogenous insulin as a means to maintain euglycemia in these patients is

as follows:

In one small observational study of 57 children with septic shock, children who died had higher peak serum glucose levels than survivors (262 versus

168 mg/dL) [25].

In one small series of 16 children with meningococcal sepsis or septic shock, hyperglycemia reflected hypoinsulinemia rather than insulin resistancein those patients with septic shock [26].

In a trial of 700 critically ill infants and children admitted to a pediatric intensive care unit (PICU) that compared conventional versus intensive control of 

serum glucose, duration of PICU stay was shortest in the intensive versus conventional treatment group (5.5 versus 6.2 days). However, hypoglycemia

(defined as blood glucose ≤40 mg/dL [2.22 mmol/L]) was more common in children receiving intensive glucose control (25 versus 1 percent,

respectively). Nine (3 percent) patients died in the intensively treated group versus 20 (6 percent) in the conventional group (p = 0.038) [ 27]. At a

median of four years of follow-up, children who had been treated with tight glycemic control during their ICU admission did not have a worse measure of 

intelligence than those who had received usual care [28].

In a trial of 980 children (0 to 36 months of age), undergoing surgery with cardiopulmonary bypass randomized to either tight glycemic control (with the

use of an insulin-dosing algorithm) targeting a blood glucose level of 80 to 110 mg/dL (4.44 to 6.12 mmol/L) or standard care in the cardiac intensive

care unit, no difference was found in the rate of health care-associated infections (8.6 versus 9.9 per 1000 patient-days) or other secondary outcomes

[29]. This study used continuous glucose monitoring to guide the frequency of blood glucose measurement and to detect impending hypoglycemia,

with only 3 percent of the patients in the tight glycemic control group exhibiting severe hypoglycemia (blood glucose <40 mg/dl [2.22 mmol/L]).

Taken together, the evidence suggests that there are no clear benefits to tight glycemic control in critically ill children. Until further data are available, insulin

therapy is warranted to avoid long periods of hyperglycemia >180 mg/dL (9.99 mmol/L) while also avoiding hypoglycemia. We do not advocate tight glycemic

control. However, there is no universally accepted insulin regimen, and the optimal approach to hyperglycemia in children with septic shock awaits further 

study.

Glycemic control in adults with critical illness is discussed separately. (See "Glycemic control and intensive insulin therapy in critical illness", section on

'Glycemic control'.)

Avoid hypocalcemia — Adequate calcium stores are essential for maintaining myocardial contractility. Thus, ionized blood calcium levels should be

monitored every one to two hours during initial management of septic shock. Patients with persistent shock and an ionized calcium <1.1 mmol/L (4.8 mg/dL)

or those with symptomatic hypocalcemia (eg, positive Chvostek or Trousseau signs, seizures, prolonged QT interval on EKG, or cardiac arrhythmias) in

association with a an ionized calcium <1.1 mmol/L (4.8 mg/dL) should undergo correction with calcium gluconate 10 percent solution in a dose of 50 mg/kg

(0.5 mL/kg), maximum dose 2 g (20 mL) by slow intravenous or intraosseous infusion over five minutes. This suggested dose is equivalent to elemental

calcium 5 mg/kg (0.15 mmol/kg), up to 180 mg elemental (4.5 mmol) per single dose

Calcium should be administered in a larger vein or, preferably, a central line. Sodium bicarbonate should not be introduced into the IV or IO without flushing

before and after administration because of potential precipitation.

Calcium chloride 10 percent in a dose of 10 to 20 mg/kg (0.1 to 0.2 mL/kg), maximum dose 1 g (10 mL) provides an equivalent dose but should only be

administered through a central line. Patients receiving a calcium infusion warrant continuous cardiac monitoring.

Treat known hormonal deficiencies — Patients with septic shock who are receiving replacement therapy for adrenal insufficiency should receive stress

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doses of corticosteroids. (See 'Address adrenal insufficiency' below.)

Similarly, children with septic shock and hypothyroidism should continue to receive thyroid replacement with levothyroxine [24]. (See "Treatment and

prognosis of congenital hypothyroidism", section on 'Dose of L-T4' and "Acquired hypothyroidism in childhood and adolescence", section on 'T4 dose'.)

REFRACTORY SEPTIC SHOCK — The initial treatment of septic shock including management recommendations for fluid-refractory septic shock are

described in the algorithm and discussed in detail separately (algorithm 1).

Fluid-refractory, catecholamine-resistant shock is defined as cardiovascular dysfunction despite at least 60 mL/kg of fluid resuscitation and dopamine ≥10

mcg/kg/min and/or direct-acting catecholamines (epinephrine, norepinephrine). Principles of management for children with refractory septic shock include

treatment of reversible etiologies, stress dose corticosteroid therapy for patients with absolute adrenal insufficiency, and combination vasoactive drug therapy

targeted to maintaining central venous oxygen saturation ≥70 percent and normalizing blood lactate levels.

 Although cardiac index targets are mentioned in previous pediatric septic shock guidelines [24], evidence of improved outcomes from routine measurement of 

cardiac index is lacking (algorithm 1). If performed, the target range is 3.3 to 6.0 L/min/m2.

Treat reversible etiologies — Pneumothorax, pericardial tamponade, and intra-abdominal hypertension (eg, peritonitis or ascites) comprise mechanical

causes of shock that can be reversed by chest tube thoracostomy, pericardiocentesis, or abdominal decompression surgery, respectively. (See "Placement

and management of thoracostomy tubes", section on 'Tube thoracostomy' and "Emergency pericardiocentesis", section on 'Technique overview'.)

Drainage or debridement of infection sites (eg, necrotizing fasciitis) or broadening of antimicrobial coverage are additional actions that may be warranted. (See

'Eradicate infection' above and "Necrotizing soft tissue infections", section on 'Treatment'.)

Uncontrolled hemorrhage, typically caused by spontaneous bleeding secondary to disseminated intravascular coagulopathy warrants timely administration of 

blood and blood products. (See 'Treat disseminated intravascular coagulation' above.)

In rare instances, persistent shock may reflect anaphylaxis to administered antibiotic agents. These patients warrant treatment with antihistamines,

epinephrine, corticosteroids, and removal of the inciting agent (table 3). (See "Anaphylaxis: Rapid recognition and treatment", section on 'Immediate

management'.)

Obtain cardiac evaluation — Patients with refractory septic shock warrant an electrocardiogram to assess for signs of myocardial ischemia or infarction

and heart failure. Pediatric cardiology consultation and echocardiography is also advised to assess for signs of myocarditis or, especially in neonates and

young infants, signs of congenital heart disease.

Patients with myocarditis diagnosed by endomyocardial biopsy may benefit from intravenous gamma globulin, although evidence is very limited.

Corticosteroids or other immunosuppressive agents may be appropriate for patients with myocarditis caused by systemic autoimmune disease in addition to

infection. (See "Treatment and prognosis of myocarditis in children", section on 'Immunosuppressive therapy'.)

Address adrenal insufficiency — Adrenal insufficiency is a clinical condition frequently associated with fluid- and catecholamine-resistant septic shock

[24,30,31]. We suggest that children with fluid-refractory, catecholamine-resistant septic shock receive stress dose glucocorticoids (eg, hydrocortisone 50 to

100 mg/m2 per dose or 1 to 2 mg/kg [maximum 100 mg] per dose followed by 50 to 100 mg/m2 [1 to 2 mg/kg [maximum 100 mg] per day either given

continuously or divided every four or six hours) [12,24,32-35]. Corticosteroid therapy should be discontinued when the patient becomes hemodynamically

stable and no longer requires vasoactive medication administration. Practice varies regarding whether corticosteroids are abruptly discontinued or tapered in

children with septic shock. Adult guidelines suggest tapering of corticosteroids but there is insufficient data in children. However, tapering is suggested if duration of corticosteroid use is long enough to potentially have caused adrenal suppression or adrenal suppression is identified by provocative testing. (See

"Corticosteroid therapy in septic shock", section on 'Administration'.)

Stress-dose corticosteroids should not be given to children with septic shock who never required or who no longer require vasopressor support unless the

patient has pre-existing known adrenal insufficiency.

Whether to use baseline cortisol measurements, adrenocorticotropin stimulation testing, or persistent hemodynamic instability alone as indicators for 

initiating and continuing corticosteroid therapy in children with refractory septic shock is debated and evidence for the best approach is lacking.

 Adrenal insufficiency (AI) is often defined in the critically ill pediatric population by an insufficient response to an adrenocorticotropic hormone (ACTH)

stimulation test with a change in cortisol from baseline to one hour after the intravenous cosyntropin of <9 mcg/dL. Using this definition, one multicenter study

showed that 30 percent of 381 critically ill children met criteria for AI during the first day of intensive care with a similar frequency occurring in the 59 patients

with sepsis [36]. Patients receiving catecholamines had a higher rate of AI (43 percent). The median baseline cortisol was 28.6 ug/dL in the children with AI,

versus 16.7 in those without AI. Among patients who did not receive corticosteroids and were re-tested 24 hours later, <20 percent met criteria for AI. Thus,

 AI can exist in critically ill patients with a relatively high random cortisol level, and AI can resolve without specific treatment. These findings have led some

experts to suggest the use of stress dose corticosteroids in children with refractory septic shock without specific testing for AI.

Corticosteroids are not without risk and should not be routinely used in children with septic shock. In an observational study of 6693 children with severe

sepsis treated in children’s hospitals, corticosteroid treatment was associated with clinically significantly increased mortality (adjusted odds ratio 1.9 [95% CI

1.7, 2.1) [37]. Neonates who received ≥2 days of corticosteroids had a greater absolute increase in mortality than older patients (12 percent versus 6 percent

increased mortality). Thus, further evidence is needed to better guide the use of corticosteroid administration in children with septic shock, including those

patients who are most likely to benefit or experience adverse effects.

Combination vasoactive drug therapy — The ongoing management of vasoactive drug therapy in children with septic shock should be performed by

clinicians with pediatric critical care expertise whenever possible. The approach provided here is for patients with septic shock who have already received a

rapid infusion of at least 40 to 60 mL/kg of crystalloid and continuous infusions of dopamine or epinephrine (patients with cold shock) or norepinephrine

(patients with warm shock) (algorithm 1).

The physical findings of cold and warm shock are discussed separately. (See "Systemic inflammatory response syndrome (SIRS) and sepsis in children:

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

 Additional vasoactive therapy should be based upon the type of persistent shock (cold or warm shock) and the central venous oxygen saturation (ScvO2) asfollows (algorithm 1) [24]:

Warm shock with low blood pressure, ScvO2 <70 percent – If initially receiving dopamine, addition of a norepinephrine infusion is warranted.

Patients who do not respond to norepinephrine infusion may receive vasopressin or its long-acting formulation, terlipressin, if available, although use of 

these agents is controversial [24]. Case reports, case series, and one trial indicate that administration of either vasopressin or terlipressin is

associated with an increase in mean arterial blood pressure and urine output in children with fluid-refractory, catecholamine-resistant septic shock [ 38-

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40]. However, in a multicenter trial of 65 children with vasodilatory shock, low-dose vasopressin did not decrease the time to hemodynamic stability off 

vasopressor agents versus placebo (49.7 versus 47.1 hours) [41]. Patients receiving low-dose vasopressin had higher mortality (30 versus 16 percent)

although this difference was not statistically significant.

Cold shock with normal or low blood pressure, ScvO2 <70 percent – If initially receiving dopamine, addition of an epinephrine infusion is

warranted.

If ScvO2 remains below 70 percent, addition of agents with inotropic properties and afterload reduction (eg, dobutamine, milrinone) or rapid-acting

vasodilators for afterload reduction (eg, nitroprusside) may be helpful (algorithm 1) [12]. Since hypotension could be exacerbated by addition of 

vasodilating agents, these should be titrated carefully with close attention to hemodynamic changes. Vasodilators should be discontinued if 

hypotension worsens.

In a small trial of 12 children with refractory catecholamine-resistant shock, administration of milrinone was associated with improved cardiac index

and increased oxygen delivery although improved survival was not demonstrated [42]. Milrinone is a phosphodiesterase inhibitor that provides both

increased cardiac contractility and vasodilation with afterload reduction. However, long-term use of milrinone is associated with an increased frequency

of ventricular arrhythmias, including torsade des pointes. Patients receiving milrinone warrant close monitoring for hypotension, given its long half life.

 Alternatively, use of a vasodilator (eg, nitroprusside) for afterload reduction may be beneficial in selected patients. If nitroprusside is used, the

medication should be protected from light, and doses in excess of 1.8 mcg/kg per minute should be avoided. Concomitant administration of thiosulfate

to scavenge the cyanide produced by nitroprusside metabolism is suggested, either prophylactically or if cyanide levels are elevated.

Advanced therapies

Extracorporeal membrane oxygenation (ECMO) — We and the American College of Critical Care Medicine (ACCM) suggest that children with

persistent catecholamine-resistant shock in whom physiologic targets (eg, ScvO2 ≥70 percent) cannot be attained with fluid repletion, vasoactive infusion, and

hormonal therapy; who do not have an immediately reversible cause, such as myocarditis, pneumothorax, or pericardial effusion; and who have a high

likelihood of mortality, be evaluated for extracorporeal membrane oxygenation (ECMO) support, if available (algorithm 1) [12]. If ECMO is not available at the

facility in which the child is receiving care then the potential benefits of ECMO must be weighed against the likelihood that the patient can tolerate transfer.

Severe sepsis and septic shock were previously considered to be contraindications to extracorporeal membrane oxygenation (ECMO) [ 24]. However, more

recent data suggest that for patients who receive ECMO, survival to hospital discharge approaches 50 percent in pediatric refractory septic shock and 80

percent for neonatal refractory septic shock. As an example, in a small case series of 23 children with refractory septic shock in which central cannulation

was used to achieve higher blood flow rates, 18 (78 percent) patients survived to be decannulated off ECMO and 17 (74 percent) children survived to hospital

discharge [43]. Our experience suggests that the chances of survival in such patients with conventional therapy alone are otherwise very remote.

Intravenous immune globulin — Adjuvant therapy with intravenous immune globulin (IVIG) has been proposed but evidence for benefit in children with

septic shock remains inconclusive. A trial of polyclonal IVIG in 100 children with pediatric sepsis syndrome showed a significant reduction in mortality (28

versus 44 percent), length of stay (six versus nine days), and less progression to complications (8 versus 32 percent) [ 44]. However, a more recent

multicenter trial of polyclonal IVIG in 3493 neonates receiving antibiotics for suspected or proven serious infection found no significant difference in the rate of 

the primary outcome of death or major disability at the age of two years (relative risk, 1.00; 95% CI, 0.9 to 1.1) [ 45]. Evidence in adult patients with septic

shock suggests that IVIG has no benefit in this population. (See "Investigational and ineffective therapies for sepsis", section on 'Intravenous

immunoglobulin'.)

For patients with toxic shock syndrome, IVIG may have clinical utility. IVIG for this indication is discussed separately. (See "Staphylococcal toxic shock

syndrome", section on 'Intravenous immune globulin'.)

EXPERIMENTAL THERAPIES

Plasma exchange or plasmapheresis — There has been considerable interest in extracorporeal filtration of circulating inflammatory mediators in sepsis.

 Although multiple studies in adults have been published on plasma exchange and plasmapheresis in sepsis, most are limited by small sample size at single

institutions with considerable variability in the protocols utilized. Thus, current evidence is conflicting as to clinical benefit. (See "Investigational and ineffective

therapies for sepsis", section on 'Hemofiltration'.)

In addition, the practical limitations of inserting a large catheter for plasma exchange in young children (often with disseminated intravascular coagulopathy

and increased risk of bleeding), the intensive resources necessary to perform plasma exchange or plasmapheresis, and the potential to worsen hypotension

in hemodynamically unstable patients has limited this therapy in pediatric sepsis.

One small trial of 10 children demonstrated a survival benefit in patients with the clinical phenotype of thrombocytopenia-associated multiple organ failure or TAMOF receiving plasmapheresis versus standard therapy (five of five versus one of five surviving) [ 46]. In this study, low levels of the von Willebrand factor 

cleaving protease, ADAMTS-13, activity were reversed with daily plasma exchange, which the authors suggested as the potential benefit of this therapy. Until

further data becomes available, plasma exchange for pediatric patients with sepsis, including TAMOF with decreased ADAMTS-13 activity, remains an

experimental therapy.

Other therapies — A variety of therapies have been investigated or are being evaluated to improve clinical outcomes in sepsis. Those therapies that appear 

promising as well as ones that have been proven to be ineffective are discussed in detail separately. (See "Investigational and ineffective therapies for 

sepsis".)

GUIDELINE IMPLEMENTATION — The early recognition and management of pediatric severe sepsis and septic shock can be improved through the

establishment of institutional care guidelines. As an example, in an observational study of the impact of guidelines for sepsis management in a children’s

hospital emergency department versus baseline actions before implementation, significant gains were documented for several key therapeutic actions

including more timely fluid resuscitation (70 versus 43 percent receiving 20 mL/kg of normal saline in the first hour), antibiotic administration (90 versus 53

percent receiving antibiotics within three hours), and blood lactate determination (measured in 70 versus 10 percent of patients with possible septic shock)

[47]. Median length of hospital stay decreased clinically significantly after implementation of the guidelines (181 to 140 hours). Mortality was not significantly

different (6 versus 7 percent).

PROGNOSIS — Factors related to the host, site of infections, and microbiology may influence the progression from systemic inflammatory response

syndrome to severe sepsis to septic shock and provide predictors of mortality. Severity of illness, progression to multiple organ failure, and treatment

requirements are also important prognostic indicators:

Host factors – Case fatality rates in children with severe sepsis are highest for infants 1 to 12 months of age (approximately 11 percent) and are higher 

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across all age groups for children with comorbidities, especially in children with cancer or human immunodeficiency virus infection (12 to 16 percent)

[3,48].

Site of infection – Children with endocarditis, central nervous system infection, and primary bacteremia have high case fatality rates (15 to 20

percent) [3]. The case fatality rate is lowest for genitourinary tract infections (approximately 4 percent).

Microbiology – Case fatality is increased in children with pneumococcal and fungal infections (15 and 13 percent, respectively) [ 3]. Infection with

organisms resistant to antibiotics (eg, methicillin-resistant Staphylococcus aureus or vancomycin-resistant enterococcus species) is associated with

a marked increased mortality from sepsis. (See "Sepsis and the systemic inflammatory response syndrome: Definitions, epidemiology, and

prognosis", section on 'Type of infection'.)

Severity of illness – Mortality increases markedly depending upon the severity of illness in children with sepsis. As an example, in a multicenter 

observational study of 1051 children between one month and 18 years of age treated for sepsis in pediatric ICUs, mortality increased from 1 percent inchildren with sepsis to 6 percent and 34 percent in children with severe sepsis and septic shock, respectively [6].

Multiple organ failure – The development of multiple organ dysfunction indicates an increased severity of illness in patients with sepsis and is

associated with a higher mortality estimated as 0 to 7 percent for patients with one affected organ system and 20 to 50 percent with two or more failing

organ systems [3,48-50]. (See "Systemic inflammatory response syndrome (SIRS) and sepsis in children: Definitions, epidemiology, clinical

manifestations, and diagnosis", section on 'Sepsis'.)

Treatment requirements – The need for multiple vasoactive infusions predicts a poor prognosis. As an example, in an observational study of 96

episodes of pediatric septic shock in 80 patients, mortality was significantly higher for patients receiving multiple rather than one vasoactive agent (43

versus 0 percent, respectively) [48].

SUMMARY AND RECOMMENDATIONS

The rapid recognition and initial resuscitation of children with septic shock is discussed separately. (See "Septic shock: Rapid recognition and initial

resuscitation in children".)

Ongoing aggressive resuscitation should continue after the initial resuscitation of pediatric septic shock according to the principles of goal-directed

therapy, especially when managing children in whom adequate circulation has not been restored (algorithm 1). (See 'Overview' above.)

Whenever possible, children requiring resuscitation for septic shock should receive ongoing management by a pediatric critical care specialist or 

pediatrician with similar expertise in a pediatric intensive care unit. (See 'Overview' above.)

Eradication of infection can reverse septic shock. Antimicrobial treatment should be optimized based upon culture results. Source control (physical

measures undertaken to eradicate a focus of infection, to eliminate ongoing microbial contamination, and to render a site inhospitable to microbial

growth and invasion) should be undertaken when possible because localized foci of infection (ie, abscess) may not respond to antibiotics alone (table

1). (See 'Eradicate infection' above.)

During initial management, continuation of respiratory support, monitoring of tissue perfusion using physiologic indicators and target goals, aggressive

administration of fluids, and titration of vasoactive infusions continue. In addition, the clinician should determine the need for invasive monitoring via

intraarterial and central venous cannulas. (See 'Ongoing and invasive monitoring' above and "Septic shock: Rapid recognition and initial resuscitation in

children", section on 'Physiologic indicators and target goals' and 'Continue fluid administration' above.)

Maintaining adequate hemoglobin levels is a critical aspect of managing children with septic shock. We and the American College of Critical Care

Medicine (ACCM) guidelines suggest a hemoglobin goal of 10 g/dL (equivalent to 30 percent hematocrit) as a target to maintain with blood transfusion

during resuscitation and ongoing management of children with septic shock (Grade 2C). Once shock has resolved, a lower hematocrit threshold for 

blood transfusion may be safe. (See 'Blood transfusion' above.)

Platelets, fresh frozen plasma, and/or cryoprecipitate should be provided to patients with disseminated intravascular coagulopathy and significant

bleeding. (See 'Treat disseminated intravascular coagulation' above.)

Other important interventions include management of glucose abnormalities, treatment of symptomatic hypocalcemia, and replacement therapy for 

known adrenal insufficiency or hypothyroidism. (See 'Manage glucose abnormalities' above and 'Avoid hypocalcemia' above and 'Treat known hormonal

deficiencies'above.)

Principles of management for children with refractory septic shock include (see 'Refractory septic shock' above):

Treatment of reversible causes (eg, pneumothorax, pericardial tamponade, hemorrhage)

 Assessment for and treatment of adrenal insufficiency

Combination vasoactive therapy targeted to central venous oxygen saturation and other measures of tissue perfusion (eg, capillary refill time, urine

output, mental status, and serum lactate levels)

We suggest that children with refractory catecholamine-resistant septic shock receive stress dose corticosteroids (eg, hydrocortisone 50 to 100

mg/m2 per dose or 1 to 2 mg/kg [maximum 100 mg] per dose followed by 50 to 100 mg/m2 [1 to 2 mg/kg [maximum 100 mg] per day either given

continuously or divided every four or six hours) (Grade 2C). Whether to use baseline cortisol measurements, adrenocorticotropin stimulation testing,

or persistent hemodynamic instability alone as indicators for continued therapy is debated and evidence for the best approach in children is lacking.

Corticosteroid therapy should be discontinued when the patient becomes hemodynamically stable. Stress-dose corticosteroids should not be given to

children with septic shock who never required or who no longer require vasopressor support unless the patient has pre-existing known adrenal

insufficiency. (See 'Address adrenal insufficiency' above.)

We and the ACCM guidelines suggest that children with persistent catecholamine-resistant shock in whom physiologic targets (eg, ScvO 2 ≥70

percent) cannot be attained with fluid repletion, vasoactive infusion, and hormonal therapy; who do not have a reversible cause, such as myocarditis,

pneumothorax, or pericardial effusion; and who have a high likelihood of mortality, be evaluated for extracorporeal membrane oxygenation (ECMO)

support, if available (algorithm 1) (Grade 2C). If the patient is an ECMO candidate and ECMO is not available at the facility in which the child is

receiving care then the potential benefits of ECMO must be weighed against the likelihood that the patient can tolerate transfer. (See 'Extracorporeal

membrane oxygenation (ECMO)' above.)

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18. Carcillo JA, Fields AI, American College of Critical Care Medicine Task Force Committee Members. Clinical practice parameters for hemodynamicsupport of pediatric and neonatal patients in septic shock. Crit Care Med 2002; 30:1365.

19. Foland JA, Fortenberry JD, Warshaw BL, et al. Fluid overload before continuous hemofiltration and survival in critically ill children: a retrospectiveanalysis. Crit Care Med 2004; 32:1771.

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21. Karam O, Tucci M, Ducruet T, et al. Red blood cell transfusion thresholds in pediatric patients with sepsis. Pediatr Crit Care Med 2011; 12:512.

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26. van Waardenburg DA, Jansen TC, Vos GD, Buurman WA. Hyperglycemia in children with meningococcal sepsis and septic shock: the relationbetween plasma levels of insulin and inflammatory mediators. J Clin Endocrinol Metab 2006; 91:3916.

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38. Yildizdas D, Yapicioglu H, Celik U, et al. Terlipressin as a rescue therapy for catecholamine-resistant septic shock in children. Intensive Care Med2008; 34:511.

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40. Masutani S, Senzaki H, Ishido H, et al. Vasopressin in the treatment of vasodilatory shock in children. Pediatr Int 2005; 47:132.

41. Choong K, Bohn D, Fraser DD, et al. Vasopressin in pediatric vasodilatory shock: a multicenter randomized controlled trial. Am J Respir Crit Care Med2009; 180:632.

42. Barton P, Garcia J, Kouatli A, et al. Hemodynamic effects of i.v. milrinone lactate in pediatric patients with septic shock. A prospective, double-blinded,randomized, placebo-controlled, interventional study. Chest 1996; 109:1302.

43. MacLaren G, Butt W, Best D, Donath S. Central extracorporeal membrane oxygenation for refractory pediatric septic shock. Pediatr Crit Care Med2011; 12:133.

44. El-Nawawy A, El-Kinany H, Hamdy El-Sayed M, Boshra N. Intravenous polyclonal immunoglobulin administration to sepsis syndrome patients: aprospective study in a pediatric intensive care unit. J Trop Pediatr 2005; 51:271.

45. INIS Collaborative Group, Brocklehurst P, Farrell B, et al. Treatment of neonatal sepsis with intravenous immune globulin. N Engl J Med 2011;

365:1201.46. Nguyen TC, Han YY, Kiss JE, et al. Intensive plasma exchange increases a disintegrin and metalloprotease with thrombospondin motifs-13 activity and

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47. Larsen GY, Mecham N, Greenberg R. An emergency department septic shock protocol and care guideline for children initiated at triage. Pediatrics2011; 127:e1585.

48. Kutko MC, Calarco MP, Flaherty MB, et al. Mortality rates in pediatric septic shock with and without multiple organ system failure. Pediatr Crit CareMed 2003; 4:333.

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Topic 86881 Version 5.0

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GRAPHICS

Recommendations for stepwise management of hemodynamic support in

infants and children with sepsis

Algorithm for time sensitive, goal-directed stepwise management of hemodynamic

support in infants and children. Proceed to next step if shock persists. (1) First hourgoals—Restore 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 goals—If shock is notreversed, intervene to restore and maintain normal perfusion pressure (mean arterial

pressure [MAP]-central venous pressure [CVP]) for age, central venous O2 saturation

>70 percent, and CI >3.3, <6.0 L/min/m2 in pediatric intensive care unit (PICU).Hgb: hemoglob in; PICCO: pulse contour cardiac ou tput; FATD: femoral arterial thermodilution;ECMO: extracorporeal membrane oxygenation; CI: cardiac index; CRRT: continuous renalreplacement the rapy; IV: intravenous ; IO: inteross eous; IM: intramuscular.Reproduced with permission from: Brierley J, Carcillo JA, Choong K, et al. Clinical practice parametersfor hemodynamic support of pediatric and neonatal septic shock: 2007 update from the American

College of Critical Care Medicine. Crit Care Med 2009; 37:666. Copyright © 2009 L ippincott Williams &Wilkins.

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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 (if removed)

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 of Sepsis, Springer-Verlag, Berlin, 1995, p.73.

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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 <50 to 65 mg/dL)

Sweating

Tachycardia

Palpitations

Tremor

Nervousness

Hunger

Paresthesias

Pallor

- Neuroglycopenia

Irritability

Confusion

Uncharacteristic behavior

Weakness

Seizures

Coma

Occasionally, transient focal neurologic deficits

Diagnosis

Obtain rapid beds ide blood glucose concentration

Confirm the presence of hypoglycemia with a simultaneously drawn plasma glucose

Treat, as outlined be low, if the bedside value is low (<70 mg/dL [3.89 mmol/L]) in symptomatic patients

Obtain a blood sample for additional diagnostic studies prior to glucose administration, if possible, and collect the first voidedurine after the hypoglycemic event in all infants and young children who are not being treated for diabetes mellitus or do not

have a known cause for hypoglycemiaΔ

Treatment

Do not delay treatment if symptomatic hypoglycemia is suspected. However, every reasonable effort should be made toobtain a rapid blood glucose measurement prior to administering glucose.

Give glucose based upon the patients level of consciousness and ability to swallow safely (ie, alert enough to do so andwith intact gag reflex) as follows:

Conscious and able to drink and swallow safely:

Administer 0.3 grams/kg (10 to 20 grams) of a rapidly-absorbed carbohydrate (eg, 2 to 3 glucose tablets, a tube of gel with 15grams, 4 oz (120 mL) sweetened fruit juice, non-diet soda, or a teaspoon (5 mL) of honey or table sugar. May repeat in 10 to 15minutes.

Altered mental status, unable to swallow, or does not respond to oral glucose administration within 15 minutes:

Give an initial IV bolus of glucose of 0.25 grams/kg of dextrose (maximum single dose 25 grams). ◊ The volume and concentration of glucose bolus is infused slowly at 2 to 3 mL per minute and based upon age:

2.5 mL/kg of 10 percent dextrose solution (D10W) in infants and children up to 12 years of age (10 percent dextrose is 100

mg/mL)1 mL/kg of 25 percent dextrose (D25W) or 0.5 mL/kg of 50 percent dextrose (D50W) in adolescents (25 percent dextrose is 250mg/mL; 50 percent dextrose is 500 mg/mL)

Unable to receive oral glucose and unable to obtain IV access:

Give glucagon 0.03 mg/kg IM or SQ (maximum dose 1 mg)§:

Perform blood glucose monitoring every 10 to 15 minutes as the effects of glucagon may be transient

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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 Organization’s 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.Δ 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 of glycogen synthesis and glycogen storage disea ses).

Septic shock: Ongoing management after resuscitation in children 19-05-2013

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Rapid overview: Emergent management of anaphylaxis in infants and children*

DIAGNOSIS IS MADE CLINICALLY:

The most common s igns and symptoms a re cutaneous (eg, sudden onset of gene ralized urticaria, angioede ma, flushing, pruritus).Howe ver, 10 to 20 percent of pa tients have no skin findings.

Danger signs: Rapid progression of symptoms, evidence of respiratory distress (eg, stridor, wheezing, dyspnea, increased

work of breathing, retractions, persistent cough, cyanosis), signs of poor perfusion•, dysrhythmia, hypotension, collapse.

ACUTE MANAGEMENT:

The first and most important therapy in anaphylaxis is epinephrine. There are NO absolute contraindications to epinephrine in thesetting of a naphylaxis.

Airway: Immediate intubation if evidence of impending airway obstruction from angioedema; delay may lead to completeobs truction; intubation can be difficult and should be performed by the mos t experienced clinician a vailable; cricothyrotomy may benecessary.

IM Epinephrine (1 mg/mL preparation): Give e pineph rine 0.01 mg pe r kilogram intramuscularly (maximum per dos e: 0.5 mg),

preferably in the mid-anterolateral thigh, can repe at every 5 to 15 minutes a s ne eded. If signs of poo r perfusion• are present or

symptoms a re not responding to epinephrine injections, prepa re IV epinephrine for infusion (see below).

Place patient in recumbent position, if tolerated, and elevate lower extremities.

Oxygen: Give 6 to 8 liters pe r minute via face mask, or up to 100 percent oxygen as neede d.

Normal saline rapid bolus: Treat poor pe rfusion• with rapid infusion of 20 mL per kilogram; reevaluate and repeat fluid boluses(20 mL per kilogram) as nee ded ; massive fluid shifts w ith severe los s of intravascular volume can occur; monitor urine output.

Albuterol: For bronchos pasm resistant to IM epinephrine, give albutero l 0.15 mg per kilogram (minimum dose: 2.5 mg) in 3 mLsaline inhaled via nebulizer; repea t as ne eded.

H1 antihistamine: Cons ider giving diphenhydramine 1 mg pe r kilogram (max 40 mg) IV.

H2 antihistamine: Cons ider giving ranitidine 1 mg per kilogram (max 50 mg) IV.

Glucocorticoid: Cons ider giving methylprednisolone 1 mg per kilogram (max 125 mg) IV.

Monitoring: Continuous noninvasive hemodynamic monitoring and pulse oximetry monitoring should be performed; urine outputshould be monitored in patients receiving IV fluid resuscitation for severe hypotension or shock.

TREATMENT OF REFRACTORY SYMPTOMS:

Epinephrine infusionΔ: Patients w ith inadequate res ponse to IM epinephrine and IV saline, give epinephrine continuous infusionat 0.1 to 1 microgram pe r kilogram per minute, titrated to e ffect.

VasopressorsΔ: Patients may require large a mounts of IV crystalloid to maintain blood pres sure; if respo nse to e pinephrine andsaline is inadequate, dopamine (5 to 20 micrograms per kilogram per minute) can be given as continuous infusion, titrated toeffect.

* A child is de fined a s a prepubertal patient we ighing less than 40 kg.• See the topic "Asses sment of pe rfusion in pediatric resuscitation".Δ All patients receiving an infusion of epinephrine and/or another vasopressor require continuous noninvasive monitoring of bloodpressure, hea rt rate and function, and o xygen saturation. We s uggest that ped iatric centers provide instructions for prepa ration of standard concentrations and also provide charts for established infusion rate for epinephrine and other vas opresso rs in infants a ndchildren.

Septic shock: Ongoing management after resuscitation in children 19-05-2013