Pediatric sepsis resident survival guide: Difference between revisions

	Sepsis in Pediatric Patients
	Diagnostic Criteria Systemic Inflammatory Response Syndrome; Sepsis; Severe Sepsis; Septic Shock;
	Causes Children > 1 Month; Children < 1 Month;
	Focused Initial Rapid Evaluation Infants and Children; Newborns;
	Empiric Antibiotic Therapy
	Dos and Don'ts

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Latest revision as of 01:58, 26 August 2020

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Diagnostic Criteria

Systemic Inflammatory Response Syndrome

Systemic inflammatory response syndrome (SIRS) represents the complex findings resulting from systemic activation of the innate immune response triggered by localized or generalized infection, trauma, thermal injury, or sterile inflammatory processes. However, criteria for SIRS are considered to be too nonspecific to be of utility in diagnosing a cause for the syndrome or in identifying a distinct pattern of host response.^[1]^[2]

SIRS is considered to be present when patients have two or more of the following clinical findings:

Body temperature >38 °C (100.4 °F) or <36 °C (96.8 °F)
Heart rate >90 beats per minute
Hyperventilation evidenced by a respiratory rate of >20 breaths per minute or a PaCO2 <32 mm Hg
White blood cell count of >12000 cells/mm³ or <4000 cells/mm³ (>12 x 10⁹ cells/L or <4 x 10⁹ cells/L) or bandemia (>10% band forms)

Sepsis

Sepsis is defined as the presence (probable or documented) of infection together with systemic manifestations of infection. Diagnostic criteria for sepsis are as follows:

Sepsis = infection (documented or suspected) and some of the following:

General variables

Fever (>38.3°C)
Hypothermia (core temperature <36°C)
Heart rate >90/min–1 or more than two SD above the normal value for age
Tachypnea
Altered mental status
Significant edema or positive fluid balance (>20 mL/kg over 24 hr)
Hyperglycemia (plasma glucose >140mg/dL or 7.7 mmol/L) in the absence of diabetes

Inflammatory variables

Leukocytosis (WBC count >12,000 μL–1)
Leukopenia (WBC count <4000 μL–1)
Normal WBC count with greater than 10% immature forms
Plasma C-reactive protein more than two SD above the normal value
Plasma procalcitonin more than two SD above the normal value

Hemodynamic variables

Arterial hypotension (SBP <90mm Hg, MAP <70mm Hg, or an SBP decrease >40mm Hg in adults or less than two SD below normal for age)

Organ dysfunction variables

Arterial hypoxemia (Pao2/Fio2 <300)
Acute oliguria (urine output <0.5 mL/kg/hr for at least 2 hrs despite adequate fluid resuscitation)
Creatinine increase >0.5mg/dL or 44.2 μmol/L
Coagulation abnormalities (INR >1.5 or aPTT >60 s)
Ileus (absent bowel sounds)
Thrombocytopenia (platelet count <100,000 μL–1)
Hyperbilirubinemia (plasma total bilirubin >4mg/dL or 70 μmol/L)

Tissue perfusion variables

Hyperlactatemia (>1 mmol/L)
Decreased capillary refill or mottling

Severe Sepsis

Severe sepsis is defined as sepsis plus sepsis-induced organ dysfunction or tissue hypoperfusion.

Severe sepsis = sepsis-induced tissue hypoperfusion or organ dysfunction (any of the following thought to be due to the infection)

Sepsis-induced hypotension (SBP of <90 mm Hg or MAP <70 mm Hg or a SBP decrease >40 mm Hg or <2 SD below normal for age in the absence of other causes of hypotension)
Lactate above upper limits laboratory normal
Urine output <0.5 mL/kg/hr for more than 2 hrs despite adequate fluid resuscitation
Acute lung injury with PaO2/FIO2 <250 in the absence of pneumonia as infection source
Acute lung injury with PaO2/FIO2 <200 in the presence of pneumonia as infection source
Creatinine >2.0 mg/dL (176.8 μmol/L)
Bilirubin >2 mg/dL (34.2 μmol/L)
Platelet count <100,000 μL
Coagulopathy (international normalized ratio >1.5)

Septic Shock

Septic shock is defined as sepsis-induced hypotension persisting despite adequate fluid resuscitation, in the absence of other causes for hypotension.

Septic shock in adult patients refers to a state of acute circulatory failure characterized by persistent arterial hypotension unexplained by other causes.
Septic shock in pediatric patients is defined as 1) a suspected infection manifested by hypothermia or hyperthermia, and 2) clinical signs of inadequate tissue perfusion including any of the following:^[3]

Decreased or altered mental status
Decreased urine output 􏰁<1 ml/kg/h
Bounding peripheral pulses (warm shock)
Diminished peripheral pulses compared with central pulses (cold shock)
Wide pulse pressure (warm shock)
Prolonged capillary refill >􏰃2 seconds (cold shock)
Flash capillary refill (warm shock)
Mottled or cool extremities (cold shock)

Septic shock in newborns manifests as tachycardia, respiratory distress, poor feeding, poor tone, poor color, tachypnea, diarrhea, or reduced perfusion, particularly in the presence of a maternal history of chorioamnionitis or prolonged rupture of membranes.

Causes

Sepsis is a life-threatening condition and must be treated immediately irrespective of the underlying cause.

Children > 1 Month

Children < 1 Month

FIRE: Focused Initial Rapid Evaluation (Infants and Children)

Focused Initial Rapid Evaluation (FIRE) should be undertaken to identify patients requiring urgent intervention.

Abbreviations: CBC, complete blood count; CI, cardiac index; CK-MB, creatine kinase MB isoform; CVP, central venous pressure; DC, differential count; ECMO, extracorporeal membrane oxygenation; FATD, femoral arterial thermodilution; HMG, hepatomegaly; IAP, intra-abdominal pressure; ICU, intensive care unit; INR, international normalized ratio; IO, intraosseous; IV, intravenous; LFT, liver function test; MAP, mean arterial pressure; PA, pulmonary artery; PCWP, pulmonary capillary wedge pressure; PDA, patent ductus arteriosus; PT, prothrombin time; PTT, partial prothrombin time; SaO2, arterial oxygen saturation; SBP, systolic blood pressure; ScvO2, central venous oxygen saturation; SMA-7, sequential multiple analysis-7; SvO2, mixed venous oxygen saturation; VLBW, very low birth weight.

Suspected Septic Shock (details) Suspected infection manifested by hypothermia or hyperthermia Clinical signs of inadequate tissue perfusion Altered mental status Decreased urine output 􏰁<1 ml/kg/h Diminished peripheral pulses compared with central pulses (cold shock) Prolonged capillary refill >􏰃2 seconds (cold shock) Mottled or cool extremities (cold shock) Bounding peripheral pulses (warm shock) Flash capillary refill (warm shock) Wide pulse pressure (warm shock)



The First Hour of Resuscitation Secure airway ± intubation (atropine / ketamine / benzodiazepine if indicated) Administer high-flow oxygen supplementation Administer IV boluses of 20 ml/kg saline until perfusion restores or rales/HMG develop Administer empiric antibiotics (details) ± Correct hypoglycemia and hypocalcemia For Fluid Refractory Shock Place central venous line and monitor CVP Reverse cold shock by titrating dopamine or epinephrine Reverse warm shock by titrating norepinephrine Administer hydrocortisone if at risk for adrenal insufficiency Therapeutic End Points Normal mental status Urine output 􏰃>1 mL/kg/h Warm extremities Capillary refill 􏰉≤2 seconds Normal peripheral and central pulses Normal blood pressure for age Normal glucose concentration Normal ionized calcium concentration



Beyond the First Hour of Resuscitation ± Transfuse RBC if Hb <􏰁10 g/dL ± Infuse FFP if prolonged INR ± Diuretics/dialysis if fluid overloaded Adjust D10%-containing isotonic fluid to maintain normoglycemia Therapeutic End Points Normal mental status Urine output 􏰃>1 mL/kg/h Capillary refill 􏰉≤2 seconds Warm extremities Threshold heart rates Normal peripheral and central pulses Perfusion pressure appropriate for age CI 􏰃>3.3 L/min/m2 and <􏰁6.0 L/min/m2 ScvO2 >􏰃70%



For Cold Shock with Normal Blood Pressure Titrate fluid and epinephrine Maintain ScvO2 >70% and Hb >10 g/dL Add nitroprusside / nitroglycerin / milrinone with volume loading if ScvO2 <70% Consider levosimendan / enoximone in recalcitrant low CO syndrome ± Thyroid hormone replacement ± Hydrocortisone replacement For Cold Shock with Low Blood Pressure Titrate fluid and epinephrine Maintain ScvO2 >70% and Hb >10 g/dL Add norepinephrine if hypotensive Consider dobutamine / milrinone / levosimendan / enoximone if ScvO2 <70% For Warm Shock with Normal Blood Pressure Titrate fluid and norepinephrine Maintain ScvO2 >70% Consider vasopressin / terripressin / angiotensin with volume if hypotensive Consider low-dose epinephrine if ScvO2 <70%



For Cateocholamine Resistant Shock Rule out and correct occult comorbidities Pericardial effusion Pneumothorax Hypoadrenalism Hypothyroidism Active hemorrhage Increased IAP (>12 mm Hg) Necrotic tissue Inappropriate control of infection source Immunocompromised / immunosuppressive state Consider PA / PiCCO / FATD catheter placement Target CI 􏰃>3.3 L/min/m2 and <􏰁6.0 L/min/m2 ± Doppler ultrasound to guide fluid therapy Consider ECMO

FIRE: Focused Initial Rapid Evaluation (Newborns)

Focused Initial Rapid Evaluation (FIRE) should be undertaken to identify patients requiring urgent intervention.

Abbreviations: CBC, complete blood count; CI, cardiac index; CK-MB, creatine kinase MB isoform; CVP, central venous pressure; DC, differential count; ECMO, extracorporeal membrane oxygenation; FATD, femoral arterial thermodilution; HMG, hepatomegaly; IAP, intra-abdominal pressure; ICU, intensive care unit; INR, international normalized ratio; IO, intraosseous; IV, intravenous; LFT, liver function test; MAP, mean arterial pressure; PA, pulmonary artery; PCWP, pulmonary capillary wedge pressure; PDA, patent ductus arteriosus; PT, prothrombin time; PTT, partial prothrombin time; SaO2, arterial oxygen saturation; SBP, systolic blood pressure; ScvO2, central venous oxygen saturation; SMA-7, sequential multiple analysis-7; SvO2, mixed venous oxygen saturation; VLBW, very low birth weight.

Suspected Septic Shock (details) Suspected infection manifested by hypothermia or hyperthermia Inadequate tissue perfusion Poor feeding Diarrhea Poor tone Poor color Tachycardia Tachypnea Respiratory distress Maternal history of chorioamnionitis or prolonged rupture of membranes



The First Hour of Resuscitation Secure airway and maintain oxygenation / ventilation Administer IV boluses of 10 ml/kg saline until perfusion restores or HMG develops Administer prostaglandin until ductal-dependent lesion is excluded Administer empiric antibiotics (details) ± Correct hypoglycemia and hypocalcemia For Fluid Refractory Shock Titrate dopamine 5-9 mcg/kg/min Administer dobutamine up to 10 mcg/kg/min Consider epinephrine (0.05-0.3 􏰄g/kg/min) to restore blood pressure and perfusion For Persistent Pulmonary Hypertension Administer 100% oxygen Institute NaHCO3 / tromethamine until up to pH 7.50 and inhaled NO is available Hyperventilate to achieve 􏰁<5% difference in preductal and postductal SaO2 and 100% SaO2 Therapeutic End Points Normal mental status Urine output 􏰃>1 mL/kg/h Warm extremities Capillary refill 􏰉≤2 seconds Normal peripheral and central pulses Normal blood pressure for age Normal glucose concentration Normal ionized calcium concentration Difference in preductal and postductal O2 saturation 􏰁<5% SaO2 ≥95%



Beyond the First Hour of Resuscitation ± Transfuse RBC if Hb <􏰁10 g/dL ± Infuse FFP if prolonged INR ± Diuretics/dialysis if fluid overloaded Adjust D10%-containing isotonic fluid to maintain normoglycemia Therapeutic End Points Normal mental status Urine output 􏰃>1 mL/kg/h Capillary refill 􏰉≤2 seconds Warm extremities Normal peripheral and central pulses Normal blood pressure for age CI 􏰃>3.3 L/min/m2 SaO2 >95% ScvO2 >􏰃70% Difference in preductal and postductal O2 saturation 􏰁<5% Absence of right-to-left shunt, tricuspid regurgitation, or right ventricular failure Normal glucose concentration Normal ionized calcium concentration SVC flow >40 mL/kg/min Normal INR Normal anion gap Normal lactate Fluid overload <10%



For Cold Shock with LV Dysfunction Add nitroprusside / nitroglycerin / milrinone with volume loading if: ScvO2 <70% SVC flow <40 mL/kg/min CI <3.3 L/min/m2 For Cold Shock with Low Blood Pressure and RV Dysfunction Administer inhaled NO if persistent pulmonary hypertension with: ScvO2 <70% SVC flow <40 mL/kg/min CI <3.3 L/min/m2 Consider milrinone / inhaled iloprost / adenosine For Warm Shock with Low Blood Pressure Titrate fluid and norepinephrine Administer inotropes to maintain ScvO2 >70%, SVC flow >40 mL/kg/min, and CI >3.3 L/min/m2 Consider vasopressin / terripressin / angiotensin with volume if hypotensive



For Cateocholamine Resistant Shock Rule out and correct occult comorbidities Pericardial effusion Pneumothorax Hypoadrenalism Hypothyroidism Active hemorrhage Increased IAP (>12 mm Hg) Necrotic tissue Inappropriate control of infection source Immunocompromised / immunosuppressive state ± Thyroid hormone replacement ± Hydrocortisone replacement Administer pentoxifylline if VLBW newborn Consider closing PDA if hemodynamically significant Consider ECMO

Empiric Antibiotic Therapy

Children aged >1 month

Cefotaxime 50 mg/kg IV q8h OR Ceftriaxone 100 mg/kg IV q24h AND
Vancomycin 15 mg/kg IV q6h

Aztreonam 7.5 mg/kg IV q6h AND
Linezolid 10 mg/kg IV q8h

Children aged <1 month

Ampicillin 25 mg/kg IV q8h AND
Cefotaxime 50 mg/kg q12h AND
Vancomycin 15 mg/kg IV q12h (if suspecting MRSA)

Ampicillin 25 mg/kg IV q6h AND
Ceftriaxone 75 mg/kg IV q24h AND
Vancomycin 15 mg/kg IV q12h (if suspecting MRSA)

Dos and Don'ts

Initial Resuscitation

For respiratory distress and hypoxemia, start with face mask oxygen or if needed and available, high flow nasal cannula oxygen or nasopharyngeal CPAP (NP CPAP). For improved circulation, peripheral intravenous access or intraosseus access can be used for fluid resuscitation and inotrope infusion when a central line is not available. If mechanical ventilation is required then cardiovascular instability during intubation is less likely after appropriate cardiovascular resuscitation. (Grade 2C)

Initial therapeutic end points of resuscitation of septic shock: capillary refill of ≤2 secs, normal blood pressure for age, normal pulses with no differential between peripheral and central pulses, warm extremities, urine output >1 mL·kg-1·hr-1, and normal mental status. Scvo2 saturation ≥70% and cardiac index between 3.3 and 6.0 L/min/m2 should be targeted thereafter. (Grade 2C)

Follow American College of Critical Care Medicine-Pediatric Life Support (ACCM-PALS) guidelines for the management of septic shock. (Grade 1C)

Evaluate for and reverse pneumothorax, pericardial tamponade, or endocrine emergencies in patients with refractory shock. (Grade 1C)

Antibiotics and Source Control

Empiric antibiotics be administered within 1 hr of the identification of severe sepsis. Blood cultures should be obtained before administering antibiotics when possible but this should not delay administration of antibiotics. The empiric drug choice should be changed as epidemic and endemic ecologies dictate (eg H1N1, MRSA, chloroquine resistant malaria, penicillin-resistant pneumococci, recent ICU stay, neutropenia). (Grade 1D)

Clindamycin and anti-toxin therapies for toxic shock syndromes with refractory hypotension. (Grade 2D)

Early and aggressive source control. (Grade 1D)

Clostridium difficile colitis should be treated with enteral antibiotics if tolerated. Oral vancomycin is preferred for severe disease. (Grade 1A)

Fluid Resuscitation

In the industrialized world with access to inotropes and mechanical ventilation, initial resuscitation of hypovolemic shock begins with infusion of isotonic crystalloids or albumin with boluses of up to 20 mL/kg crystalloids (or albumin equivalent) over 5–10 minutes, titrated to reversing hypotension, increasing urine output, and attaining normal capillary refill, peripheral pulses, and level of consciousness without inducing hepatomegaly or rales. If hepatomegaly or rales exist then inotropic support should be implemented, not fluid resuscitation. In non-hypotensive children with severe hemolytic anemia (severe malaria or sickle cell crises) blood transfusion is considered superior to crystalloid or albumin bolusing. (Grade 2C)

Inotropes/Vasopressors/Vasodilators

Begin peripheral inotropic support until central venous access can be attained in children who are not responsive to fluid resuscitation. (Grade 2C)

Patients with low cardiac output and elevated systemic vascular resistance states with normal blood pressure be given vasodilator therapies in addition to inotropes. (Grade 2C)

Extracorporeal Membrane Oxygenation (ECMO)

Consider ECMO for refractory pediatric septic shock and respiratory failure. (Grade 2C)

Corticosteroids

Timely hydrocortisone therapy in children with fluid refractory, catecholamine resistant shock and suspected or proven absolute (classic) adrenal insufficiency. (Grade 1A)

Blood Products and Plasma Therapies

Similar hemoglobin targets in children as in adults. During resuscitation of low superior vena cava oxygen saturation shock (< 70%), hemoglobin levels of 10 g/dL are targeted. After stabilization and recovery from shock and hypoxemia then a lower target > 7.0 g/dL can be considered reasonable. (Grade 1B)

Similar platelet transfusion targets in children as in adults. (Grade 2C)

Use plasma therapies in children to correct sepsis-induced thrombotic purpura disorders, including progressive disseminated intravascular coagulation, secondary thrombotic microangiopathy, and thrombotic thrombocytopenic purpura. (Grade 2C)

Mechanical Ventilation

Lung-protective strategies during mechanical ventilation. (Grade 2C)

Sedation/Analgesia/Drug Toxicities

We recommend use of sedation with a sedation goal in critically ill mechanically ventilated patients with sepsis. (Grade 1D)

Monitor drug toxicity labs because drug metabolism is reduced during severe sepsis, putting children at greater risk of adverse drug-related events. (Grade 1C)

Glycemic Control

Control hyperglycemia using a similar target as in adults ≤ 180 mg/dL. Glucose infusion should accompany insulin therapy in newborns and children because some hyperglycemic children make no insulin whereas others are insulin resistant. (Grade 2C)

Diuretics and Renal Replacement Therapy

Use diuretics to reverse fluid overload when shock has resolved, and if unsuccessful then continuous venovenous hemofiltration (CVVH) or intermittent dialysis to prevent > 10% total body weight fluid overload. (Grade 2C)

Nutrition

Enteral nutrition given to children who can be fed enterally, and parenteral feeding in those who cannot. (Grade 2C)

References

↑ Dellinger, R. Phillip; Levy, Mitchell M.; Rhodes, Andrew; Annane, Djillali; Gerlach, Herwig; Opal, Steven M.; Sevransky, Jonathan E.; Sprung, Charles L.; Douglas, Ivor S.; Jaeschke, Roman; Osborn, Tiffany M.; Nunnally, Mark E.; Townsend, Sean R.; Reinhart, Konrad; Kleinpell, Ruth M.; Angus, Derek C.; Deutschman, Clifford S.; Machado, Flavia R.; Rubenfeld, Gordon D.; Webb, Steven A.; Beale, Richard J.; Vincent, Jean-Louis; Moreno, Rui; Surviving Sepsis Campaign Guidelines Committee including the Pediatric Subgroup (2013-02). "Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock: 2012". Critical Care Medicine. 41 (2): 580–637. doi:10.1097/CCM.0b013e31827e83af. ISSN 1530-0293. PMID 23353941. Check date values in: |date= (help)
↑ Brierley, Joe; Carcillo, Joseph A.; Choong, Karen; Cornell, Tim; Decaen, Allan; Deymann, Andreas; Doctor, Allan; Davis, Alan; Duff, John; Dugas, Marc-Andre; Duncan, Alan; Evans, Barry; Feldman, Jonathan; Felmet, Kathryn; Fisher, Gene; Frankel, Lorry; Jeffries, Howard; Greenwald, Bruce; Gutierrez, Juan; Hall, Mark; Han, Yong Y.; Hanson, James; Hazelzet, Jan; Hernan, Lynn; Kiff, Jane; Kissoon, Niranjan; Kon, Alexander; Irazuzta, Jose; Irazusta, Jose; Lin, John; Lorts, Angie; Mariscalco, Michelle; Mehta, Renuka; Nadel, Simon; Nguyen, Trung; Nicholson, Carol; Peters, Mark; Okhuysen-Cawley, Regina; Poulton, Tom; Relves, Monica; Rodriguez, Agustin; Rozenfeld, Ranna; Schnitzler, Eduardo; Shanley, Tom; Kache, Saraswati; Skache, Sara; Skippen, Peter; Torres, Adalberto; von Dessauer, Bettina; Weingarten, Jacki; Yeh, Timothy; Zaritsky, Arno; Stojadinovic, Bonnie; Zimmerman, Jerry; Zuckerberg, Aaron (2009-02). "Clinical practice parameters for hemodynamic support of pediatric and neonatal septic shock: 2007 update from the American College of Critical Care Medicine". Critical Care Medicine. 37 (2): 666–688. doi:10.1097/CCM.0b013e31819323c6. ISSN 1530-0293. PMID 19325359. Check date values in: |date= (help)
↑ Brierley, Joe; Carcillo, Joseph A.; Choong, Karen; Cornell, Tim; Decaen, Allan; Deymann, Andreas; Doctor, Allan; Davis, Alan; Duff, John; Dugas, Marc-Andre; Duncan, Alan; Evans, Barry; Feldman, Jonathan; Felmet, Kathryn; Fisher, Gene; Frankel, Lorry; Jeffries, Howard; Greenwald, Bruce; Gutierrez, Juan; Hall, Mark; Han, Yong Y.; Hanson, James; Hazelzet, Jan; Hernan, Lynn; Kiff, Jane; Kissoon, Niranjan; Kon, Alexander; Irazuzta, Jose; Irazusta, Jose; Lin, John; Lorts, Angie; Mariscalco, Michelle; Mehta, Renuka; Nadel, Simon; Nguyen, Trung; Nicholson, Carol; Peters, Mark; Okhuysen-Cawley, Regina; Poulton, Tom; Relves, Monica; Rodriguez, Agustin; Rozenfeld, Ranna; Schnitzler, Eduardo; Shanley, Tom; Kache, Saraswati; Skache, Sara; Skippen, Peter; Torres, Adalberto; von Dessauer, Bettina; Weingarten, Jacki; Yeh, Timothy; Zaritsky, Arno; Stojadinovic, Bonnie; Zimmerman, Jerry; Zuckerberg, Aaron (2009-02). "Clinical practice parameters for hemodynamic support of pediatric and neonatal septic shock: 2007 update from the American College of Critical Care Medicine". Critical Care Medicine. 37 (2): 666–688. doi:10.1097/CCM.0b013e31819323c6. ISSN 1530-0293. PMID 19325359. Check date values in: |date= (help)

[1] Dellinger, R. Phillip; Levy, Mitchell M.; Rhodes, Andrew; Annane, Djillali; Gerlach, Herwig; Opal, Steven M.; Sevransky, Jonathan E.; Sprung, Charles L.; Douglas, Ivor S.; Jaeschke, Roman; Osborn, Tiffany M.; Nunnally, Mark E.; Townsend, Sean R.; Reinhart, Konrad; Kleinpell, Ruth M.; Angus, Derek C.; Deutschman, Clifford S.; Machado, Flavia R.; Rubenfeld, Gordon D.; Webb, Steven A.; Beale, Richard J.; Vincent, Jean-Louis; Moreno, Rui; Surviving Sepsis Campaign Guidelines Committee including the Pediatric Subgroup (2013-02). "Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock: 2012". Critical Care Medicine. 41 (2): 580–637. doi:10.1097/CCM.0b013e31827e83af. ISSN 1530-0293. PMID 23353941. Check date values in: |date= (help)

[2] Brierley, Joe; Carcillo, Joseph A.; Choong, Karen; Cornell, Tim; Decaen, Allan; Deymann, Andreas; Doctor, Allan; Davis, Alan; Duff, John; Dugas, Marc-Andre; Duncan, Alan; Evans, Barry; Feldman, Jonathan; Felmet, Kathryn; Fisher, Gene; Frankel, Lorry; Jeffries, Howard; Greenwald, Bruce; Gutierrez, Juan; Hall, Mark; Han, Yong Y.; Hanson, James; Hazelzet, Jan; Hernan, Lynn; Kiff, Jane; Kissoon, Niranjan; Kon, Alexander; Irazuzta, Jose; Irazusta, Jose; Lin, John; Lorts, Angie; Mariscalco, Michelle; Mehta, Renuka; Nadel, Simon; Nguyen, Trung; Nicholson, Carol; Peters, Mark; Okhuysen-Cawley, Regina; Poulton, Tom; Relves, Monica; Rodriguez, Agustin; Rozenfeld, Ranna; Schnitzler, Eduardo; Shanley, Tom; Kache, Saraswati; Skache, Sara; Skippen, Peter; Torres, Adalberto; von Dessauer, Bettina; Weingarten, Jacki; Yeh, Timothy; Zaritsky, Arno; Stojadinovic, Bonnie; Zimmerman, Jerry; Zuckerberg, Aaron (2009-02). "Clinical practice parameters for hemodynamic support of pediatric and neonatal septic shock: 2007 update from the American College of Critical Care Medicine". Critical Care Medicine. 37 (2): 666–688. doi:10.1097/CCM.0b013e31819323c6. ISSN 1530-0293. PMID 19325359. Check date values in: |date= (help)

[3] Brierley, Joe; Carcillo, Joseph A.; Choong, Karen; Cornell, Tim; Decaen, Allan; Deymann, Andreas; Doctor, Allan; Davis, Alan; Duff, John; Dugas, Marc-Andre; Duncan, Alan; Evans, Barry; Feldman, Jonathan; Felmet, Kathryn; Fisher, Gene; Frankel, Lorry; Jeffries, Howard; Greenwald, Bruce; Gutierrez, Juan; Hall, Mark; Han, Yong Y.; Hanson, James; Hazelzet, Jan; Hernan, Lynn; Kiff, Jane; Kissoon, Niranjan; Kon, Alexander; Irazuzta, Jose; Irazusta, Jose; Lin, John; Lorts, Angie; Mariscalco, Michelle; Mehta, Renuka; Nadel, Simon; Nguyen, Trung; Nicholson, Carol; Peters, Mark; Okhuysen-Cawley, Regina; Poulton, Tom; Relves, Monica; Rodriguez, Agustin; Rozenfeld, Ranna; Schnitzler, Eduardo; Shanley, Tom; Kache, Saraswati; Skache, Sara; Skippen, Peter; Torres, Adalberto; von Dessauer, Bettina; Weingarten, Jacki; Yeh, Timothy; Zaritsky, Arno; Stojadinovic, Bonnie; Zimmerman, Jerry; Zuckerberg, Aaron (2009-02). "Clinical practice parameters for hemodynamic support of pediatric and neonatal septic shock: 2007 update from the American College of Critical Care Medicine". Critical Care Medicine. 37 (2): 666–688. doi:10.1097/CCM.0b013e31819323c6. ISSN 1530-0293. PMID 19325359. Check date values in: |date= (help)

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-! style="font-size: 90%; padding: 0 5px; background: #DCDCDC; border-radius: 5px 5px 5px 5px;" align=left | [[{{PAGENAME}}#FIRE: Focused Initial Rapid Evaluation|Focused Initial Rapid Evaluation]]
+| style="padding: 2px 10px; background: #4479BA; border-radius: 5px 5px 5px 5px; text-shadow: 0 -1px 0 rgba(0, 0, 0, 0.5); box-shadow: 0 1px 1px rgba(0, 0, 0, 0.5);" |
+[[{{PAGENAME}}#Empiric Antibiotic Therapy|{{fontcolor|#F8F8FF|Empiric Antibiotic Therapy}}]]
 |-
-! style="font-size: 90%; padding: 0 5px; background: #DCDCDC; border-radius: 5px 5px 5px 5px;" align=left | [[{{PAGENAME}}#Empiric Antibiotic Therapy|Empiric Therapy]]
+| style="padding: 2px 10px; background: #4479BA; border-radius: 5px 5px 5px 5px; text-shadow: 0 -1px 0 rgba(0, 0, 0, 0.5); box-shadow: 0 1px 1px rgba(0, 0, 0, 0.5);" |
-|-
+[[{{PAGENAME}}#Dos and Don'ts|{{fontcolor|#F8F8FF|Dos and Don'ts}}]]
-! style="font-size: 90%; padding: 0 5px; background: #DCDCDC; border-radius: 5px 5px 5px 5px;" align=left | [[{{PAGENAME}}#Dos|Dos]]
-|-
-! style="font-size: 90%; padding: 0 5px; background: #DCDCDC; border-radius: 5px 5px 5px 5px;" align=left | [[{{PAGENAME}}#Don'ts|Don'ts]]
 |}
 __NOTOC____NOEDITSECTION__
 {{Main|Sepsis}}
-{{Seealso|Neonatal sepsis resident survival guide}}
+{{See also|Sepsis resident survival guide}}
-{{CMG}}; {{AE}} {{AZ}}; {{VB}}
+{{CMG}}
+==Diagnostic Criteria==
-==Diagnostic Criteria==
 ===Systemic Inflammatory Response Syndrome===
-Systemic inflammatory response syndrome (SIRS) represents the complex findings resulting from systemic activation of the innate immune response triggered by localized or generalized infection, trauma, thermal injury, or sterile inflammatory processes. However, criteria for SIRS are considered to be too nonspecific to be of utility in diagnosing a cause for the syndrome or in identifying a distinct pattern of host response.<ref>{{Cite journal| doi = 10.1097/CCM.0b013e31827e83af| issn = 1530-0293| volume = 41| issue = 2| pages = 580–637| last1 = Dellinger| first1 = R. Phillip| last2 = Levy| first2 = Mitchell M.| last3 = Rhodes| first3 = Andrew| last4 = Annane| first4 = Djillali| last5 = Gerlach| first5 = Herwig| last6 = Opal| first6 = Steven M.| last7 = Sevransky| first7 = Jonathan E.| last8 = Sprung| first8 = Charles L.| last9 = Douglas| first9 = Ivor S.| last10 = Jaeschke| first10 = Roman| last11 = Osborn| first11 = Tiffany M.| last12 = Nunnally| first12 = Mark E.| last13 = Townsend| first13 = Sean R.| last14 = Reinhart| first14 = Konrad| last15 = Kleinpell| first15 = Ruth M.| last16 = Angus| first16 = Derek C.| last17 = Deutschman| first17 = Clifford S.| last18 = Machado| first18 = Flavia R.| last19 = Rubenfeld| first19 = Gordon D.| last20 = Webb| first20 = Steven A.| last21 = Beale| first21 = Richard J.| last22 = Vincent| first22 = Jean-Louis| last23 = Moreno| first23 = Rui| last24 = Surviving Sepsis Campaign Guidelines Committee including the Pediatric Subgroup| title = Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock: 2012| journal = Critical Care Medicine| date = 2013-02| pmid = 23353941}}</ref>
+Systemic inflammatory response syndrome (SIRS) represents the complex findings resulting from systemic activation of the innate immune response triggered by localized or generalized infection, trauma, thermal injury, or sterile inflammatory processes. However, criteria for SIRS are considered to be too nonspecific to be of utility in diagnosing a cause for the syndrome or in identifying a distinct pattern of host response.<ref>{{Cite journal| doi = 10.1097/CCM.0b013e31827e83af| issn = 1530-0293| volume = 41| issue = 2| pages = 580–637| last1 = Dellinger| first1 = R. Phillip| last2 = Levy| first2 = Mitchell M.| last3 = Rhodes| first3 = Andrew| last4 = Annane| first4 = Djillali| last5 = Gerlach| first5 = Herwig| last6 = Opal| first6 = Steven M.| last7 = Sevransky| first7 = Jonathan E.| last8 = Sprung| first8 = Charles L.| last9 = Douglas| first9 = Ivor S.| last10 = Jaeschke| first10 = Roman| last11 = Osborn| first11 = Tiffany M.| last12 = Nunnally| first12 = Mark E.| last13 = Townsend| first13 = Sean R.| last14 = Reinhart| first14 = Konrad| last15 = Kleinpell| first15 = Ruth M.| last16 = Angus| first16 = Derek C.| last17 = Deutschman| first17 = Clifford S.| last18 = Machado| first18 = Flavia R.| last19 = Rubenfeld| first19 = Gordon D.| last20 = Webb| first20 = Steven A.| last21 = Beale| first21 = Richard J.| last22 = Vincent| first22 = Jean-Louis| last23 = Moreno| first23 = Rui| last24 = Surviving Sepsis Campaign Guidelines Committee including the Pediatric Subgroup| title = Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock: 2012| journal = Critical Care Medicine| date = 2013-02| pmid = 23353941}}</ref><ref>{{Cite journal| doi = 10.1097/CCM.0b013e31819323c6| issn = 1530-0293| volume = 37| issue = 2| pages = 666–688| last1 = Brierley| first1 = Joe| last2 = Carcillo| first2 = Joseph A.| last3 = Choong| first3 = Karen| last4 = Cornell| first4 = Tim| last5 = Decaen| first5 = Allan| last6 = Deymann| first6 = Andreas| last7 = Doctor| first7 = Allan| last8 = Davis| first8 = Alan| last9 = Duff| first9 = John| last10 = Dugas| first10 = Marc-Andre| last11 = Duncan| first11 = Alan| last12 = Evans| first12 = Barry| last13 = Feldman| first13 = Jonathan| last14 = Felmet| first14 = Kathryn| last15 = Fisher| first15 = Gene| last16 = Frankel| first16 = Lorry| last17 = Jeffries| first17 = Howard| last18 = Greenwald| first18 = Bruce| last19 = Gutierrez| first19 = Juan| last20 = Hall| first20 = Mark| last21 = Han| first21 = Yong Y.| last22 = Hanson| first22 = James| last23 = Hazelzet| first23 = Jan| last24 = Hernan| first24 = Lynn| last25 = Kiff| first25 = Jane| last26 = Kissoon| first26 = Niranjan| last27 = Kon| first27 = Alexander| last28 = Irazuzta| first28 = Jose| last29 = Irazusta| first29 = Jose| last30 = Lin| first30 = John| last31 = Lorts| first31 = Angie| last32 = Mariscalco| first32 = Michelle| last33 = Mehta| first33 = Renuka| last34 = Nadel| first34 = Simon| last35 = Nguyen| first35 = Trung| last36 = Nicholson| first36 = Carol| last37 = Peters| first37 = Mark| last38 = Okhuysen-Cawley| first38 = Regina| last39 = Poulton| first39 = Tom| last40 = Relves| first40 = Monica| last41 = Rodriguez| first41 = Agustin| last42 = Rozenfeld| first42 = Ranna| last43 = Schnitzler| first43 = Eduardo| last44 = Shanley| first44 = Tom| last45 = Kache| first45 = Saraswati| last46 = Skache| first46 = Sara| last47 = Skippen| first47 = Peter| last48 = Torres| first48 = Adalberto| last49 = von Dessauer| first49 = Bettina| last50 = Weingarten| first50 = Jacki| last51 = Yeh| first51 = Timothy| last52 = Zaritsky| first52 = Arno| last53 = Stojadinovic| first53 = Bonnie| last54 = Zimmerman| first54 = Jerry| last55 = Zuckerberg| first55 = Aaron| title = Clinical practice parameters for hemodynamic support of pediatric and neonatal septic shock: 2007 update from the American College of Critical Care Medicine| journal = Critical Care Medicine| date = 2009-02| pmid = 19325359}}</ref>
 {| style="margin: 5px 10px; width: 600px;"
@@ Line 96: / Line 106: @@
 Septic shock is defined as sepsis-induced hypotension persisting despite adequate fluid resuscitation, in the absence of other causes for hypotension.
 * '''Septic shock in adult patients''' refers to a state of acute circulatory failure characterized by persistent arterial hypotension unexplained by other causes.
-* '''Septic shock in pediatric patients''' is defined as a tachycardia (may be absent in the hypothermic patient) with signs of decreased perfusion including decreased peripheral pulses compared with central pulses, altered alertness, flash capillary refill or capillary refill 􏰀2 seconds, mottled or cool extremities, or decreased urine output.
+* '''Septic shock in pediatric patients''' is defined as 1) a suspected infection manifested by hypothermia or hyperthermia, and 2) clinical signs of inadequate tissue perfusion including any of the following:<ref>{{Cite journal| doi = 10.1097/CCM.0b013e31819323c6| issn = 1530-0293| volume = 37| issue = 2| pages = 666–688| last1 = Brierley| first1 = Joe| last2 = Carcillo| first2 = Joseph A.| last3 = Choong| first3 = Karen| last4 = Cornell| first4 = Tim| last5 = Decaen| first5 = Allan| last6 = Deymann| first6 = Andreas| last7 = Doctor| first7 = Allan| last8 = Davis| first8 = Alan| last9 = Duff| first9 = John| last10 = Dugas| first10 = Marc-Andre| last11 = Duncan| first11 = Alan| last12 = Evans| first12 = Barry| last13 = Feldman| first13 = Jonathan| last14 = Felmet| first14 = Kathryn| last15 = Fisher| first15 = Gene| last16 = Frankel| first16 = Lorry| last17 = Jeffries| first17 = Howard| last18 = Greenwald| first18 = Bruce| last19 = Gutierrez| first19 = Juan| last20 = Hall| first20 = Mark| last21 = Han| first21 = Yong Y.| last22 = Hanson| first22 = James| last23 = Hazelzet| first23 = Jan| last24 = Hernan| first24 = Lynn| last25 = Kiff| first25 = Jane| last26 = Kissoon| first26 = Niranjan| last27 = Kon| first27 = Alexander| last28 = Irazuzta| first28 = Jose| last29 = Irazusta| first29 = Jose| last30 = Lin| first30 = John| last31 = Lorts| first31 = Angie| last32 = Mariscalco| first32 = Michelle| last33 = Mehta| first33 = Renuka| last34 = Nadel| first34 = Simon| last35 = Nguyen| first35 = Trung| last36 = Nicholson| first36 = Carol| last37 = Peters| first37 = Mark| last38 = Okhuysen-Cawley| first38 = Regina| last39 = Poulton| first39 = Tom| last40 = Relves| first40 = Monica| last41 = Rodriguez| first41 = Agustin| last42 = Rozenfeld| first42 = Ranna| last43 = Schnitzler| first43 = Eduardo| last44 = Shanley| first44 = Tom| last45 = Kache| first45 = Saraswati| last46 = Skache| first46 = Sara| last47 = Skippen| first47 = Peter| last48 = Torres| first48 = Adalberto| last49 = von Dessauer| first49 = Bettina| last50 = Weingarten| first50 = Jacki| last51 = Yeh| first51 = Timothy| last52 = Zaritsky| first52 = Arno| last53 = Stojadinovic| first53 = Bonnie| last54 = Zimmerman| first54 = Jerry| last55 = Zuckerberg| first55 = Aaron| title = Clinical practice parameters for hemodynamic support of pediatric and neonatal septic shock: 2007 update from the American College of Critical Care Medicine| journal = Critical Care Medicine| date = 2009-02| pmid = 19325359}}</ref>
+:* Decreased or altered mental status
+:* Decreased urine output 􏰁&lt;1 ml/kg/h
+:* Bounding peripheral pulses (warm shock)
+:* Diminished peripheral pulses compared with central pulses (cold shock)
+:* Wide pulse pressure (warm shock)
+:* Prolonged capillary refill &gt;􏰃2 seconds (cold shock)
+:* Flash capillary refill (warm shock)
+:* Mottled or cool extremities (cold shock)
+* '''Septic shock in newborns''' manifests as tachycardia, respiratory distress, poor feeding, poor tone, poor color, tachypnea, diarrhea, or reduced perfusion, particularly in the presence of a maternal history of chorioamnionitis or prolonged rupture of membranes.
 ==Causes==
 ''Sepsis is a life-threatening condition and must be treated immediately irrespective of the underlying cause.''
-* If associated with [[community-acquired pneumonia]]
-:* ''[[Streptococcus pneumoniae]]''
-:* ''[[Staphylococcus aureus]]'' and [[MRSA]]
-:* ''[[Legionella]]''
-:* [[Gram-negative bacilli]]
-* If associated with [[urinary tract infection]]
-:* [[Aerobic]] [[gram-negative bacilli]]
-:* ''[[Enterococcus]]''
-* If associated with [[intra-abdominal infection]]
-:* [[Aerobic]] [[gram-negative bacilli]]
-:* [[Anaerobic]] [[gram-negative bacilli]]
-* If associated with [[intravenous drug use]]
-:* ''[[Staphylococcus]]''
-:* ''[[Nocardia]]''
-* If associated with [[petechiae]]
-:* ''[[Neisseria meningitidis]]''
-:* [[Rocky Mountain spotted fever]]
-==FIRE: Focused Initial Rapid Evaluation==
+===Children > 1 Month===
+* ''[[Streptococcus pneumoniae]]''
+* ''[[Neisseria meningitidis]]''
+* ''[[Staphylococcus aureus]]''
+* ''[[Haemophilus influenzae]]''
+===Children < 1 Month===
+* ''[[Streptococcus agalactiae]]''
+* ''[[Escherichia coli]]''
+* ''[[Klebsiella]]''
+* ''[[Enterobacter]]''
+* ''[[Staphylococcus aureus]]''
+* ''[[Listeria]]''
+* ''[[Salmonella]]''
+* ''[[Haemophilus influenzae]]''
+* ''[[Staphylococcus epidermidis]]''
+==FIRE: Focused Initial Rapid Evaluation (Infants and Children)==
 <span style="background: #FFF0F5; font-weight: bold; font-style: italic;">Focused Initial Rapid Evaluation (FIRE)</span> should be undertaken to identify patients requiring urgent intervention.
@@ Line 128: / Line 147: @@
 CVP, central venous pressure;
 DC, differential count;
+ECMO, extracorporeal membrane oxygenation;
+FATD, femoral arterial thermodilution;
+HMG, hepatomegaly;
+IAP, intra-abdominal pressure;
 ICU, intensive care unit;
 INR, international normalized ratio;
+IO, intraosseous;
+IV, intravenous;
 LFT, liver function test;
 MAP, mean arterial pressure;
+PA, pulmonary artery;
 PCWP, pulmonary capillary wedge pressure;
+PDA, patent ductus arteriosus;
 PT, prothrombin time;
 PTT, partial prothrombin time;
@@ Line 138: / Line 165: @@
 SBP, systolic blood pressure;
 ScvO2, central venous oxygen saturation;
+SMA-7, sequential multiple analysis-7;
 SvO2, mixed venous oxygen saturation;
-SMA-7, sequential multiple analysis-7.
+VLBW, very low birth weight.
 </span>
 <div style="font-size: 90%;">
 {{Familytree/start}}
-{{Familytree|boxstyle=width: 600px; text-align: left; font-size: 100%; padding: 0px;| | A01 | | |A01=<div style="padding: 15px;">
+{{Familytree|boxstyle=width: 600px; text-align: left; font-size: 100%; padding: 0px;| A01 | | |A01=<div style="padding: 15px;">
-<BIG>'''Suspected sepsis'''</BIG> [[Sepsis resident survival guide#Diagnostic Criteria|(details)]]
+<BIG>'''Suspected Septic Shock'''</BIG> [[Pediatric sepsis resident survival guide#Diagnostic Criteria|(details)]]
 ----
-'''Signs and Symptoms'''
+* Suspected infection manifested by hypothermia or hyperthermia
-* Fever (&gt;38.3°C)
+* Clinical signs of inadequate tissue perfusion
-* Hypothermia (core temperature &lt;36°C)
+:* Altered mental status
-* Heart rate &gt;90/min–1 or more than two SD above the normal value for age
+:* Decreased urine output 􏰁&lt;1 ml/kg/h
-* Tachypnea
+:* Diminished peripheral pulses compared with central pulses (cold shock)
-* Altered mental status
+:* Prolonged capillary refill &gt;􏰃2 seconds (cold shock)
-* Significant edema or positive fluid balance (&gt;20 mL/kg over 24 hr)
+:* Mottled or cool extremities (cold shock)
-* Hypotension (SBP &lt;90 mm Hg, MAP &lt;70 mm Hg, or an SBP decrease &gt;40 mm Hg)
+:* Bounding peripheral pulses (warm shock)
-* Hypoxemia (PaO2/FiO2 &lt;300)
+:* Flash capillary refill (warm shock)
-* Acute oliguria (urine output &lt;0.5 mL/kg/hr for at least 2 hrs despite adequate fluid resuscitation)
+:* Wide pulse pressure (warm shock)
-* Ileus (absent bowel sounds)
+</div>}}
-* Diminished capillary refill or mottling
+{{Familytree|boxstyle=width: 600px; text-align: left; font-size: 100%; padding: 0px;| |!| | | |}}
-'''Laboratory Findings'''
+{{Familytree|boxstyle=width: 600px; text-align: left; font-size: 100%; padding: 0px;| A01 | | |A01=<div style="padding: 15px;">
-* Hyperglycemia (plasma glucose &gt;140mg/dL or 7.7 mmol/L) in the absence of diabetes
+<BIG>'''The First Hour of Resuscitation'''</BIG>
-* Leukocytosis (WBC count &gt;12,000 μL–1)
+----
-* Leukopenia (WBC count &lt;4000 μL–1)
+* Secure airway ± intubation (atropine / ketamine / benzodiazepine if indicated)
-* Bandemia &gt;10% immature forms
+* Administer high-flow oxygen supplementation
-* C-reactive protein more than two SD above the normal value
+* Administer IV boluses of 20 ml/kg saline until perfusion restores or rales/HMG develop
-* Procalcitonin greater than two SD above the normal value
+* Administer empiric antibiotics [[Pediatric sepsis resident survival guide#Empiric Antibiotic Therapy|(details)]]
-* Creatinine increase &gt;0.5mg/dL or 44.2 μmol/L
+* ± Correct hypoglycemia and hypocalcemia
-* Coagulation abnormalities (INR &gt;1.5 or aPTT &gt;60 s)
+<BIG>'''For Fluid Refractory Shock'''</BIG>
-* Thrombocytopenia (platelet count &lt;100,000 μL–1)
+----
-* Hyperbilirubinemia (plasma total bilirubin &gt;4 mg/dL or 70 μmol/L)
+* Place central venous line and monitor CVP
-* Hyperlactatemia (&gt;1 mmol/L)
+* Reverse cold shock by titrating dopamine or epinephrine
+* Reverse warm shock by titrating norepinephrine
+* Administer hydrocortisone if at risk for adrenal insufficiency
+<BIG>'''Therapeutic End Points'''</BIG>
+----
+* Normal mental status
+* Urine output 􏰃&gt;1 mL/kg/h
+* Warm extremities
+* Capillary refill 􏰉≤2 seconds
+* Normal peripheral and central pulses
+* Normal blood pressure for age
+* Normal glucose concentration
+* Normal ionized calcium concentration
 </div>}}
-{{Familytree|boxstyle=width: 600px; text-align: left; font-size: 100%; padding: 0px;| | |!| | | |}}
+{{Familytree|boxstyle=width: 600px; text-align: left; font-size: 100%; padding: 0px;| |!| | | |}}
-{{Familytree|boxstyle=width: 600px; text-align: left; font-size: 100%; padding: 0px;| | B01 | | |B01=<div style="padding: 15px;">
+{{Familytree|boxstyle=width: 600px; text-align: left; font-size: 100%; padding: 0px;| A01 | | |A01=<div style="padding: 15px;">
-<BIG>'''Early Goal-Directed Therapy'''</BIG>
+<BIG>'''Beyond the First Hour of Resuscitation'''</BIG>
+----
+* ± Transfuse RBC if Hb &lt;􏰁10 g/dL
+* ± Infuse FFP if prolonged INR
+* ± Diuretics/dialysis if fluid overloaded
+* Adjust D10%-containing isotonic fluid to maintain normoglycemia
+<BIG>'''Therapeutic End Points'''</BIG>
 ----
-* Supplemental oxygen ± intubation / ventilatory support ± sedation to maintain SaO2 ≥93%
+* Normal mental status
-* Arterial and central venous line placement
+* Urine output 􏰃&gt;1 mL/kg/h
-<BIG>'''Rivers Protocol'''</BIG>
+* Capillary refill 􏰉≤2 seconds
+* Warm extremities
+* Threshold heart rates
+* Normal peripheral and central pulses
+* Perfusion pressure appropriate for age
+* CI 􏰃&gt;3.3 L/min/m2 and &lt;􏰁6.0 L/min/m2
+* ScvO2 &gt;􏰃70%
+</div>}}
+{{Familytree|boxstyle=width: 600px; text-align: left; font-size: 100%; padding: 0px;| |!| | | |}}
+{{Familytree|boxstyle=width: 600px; text-align: left; font-size: 100%; padding: 0px;| A01 | | |A01=<div style="padding: 15px;">
+<BIG>'''For Cold Shock with Normal Blood Pressure'''</BIG>
 ----
-* Infuse a 500 ml bolus of crystalloid q 30 minutes to maintain CVP at 8–12 mm Hg.
+* Titrate fluid and epinephrine
-* If MAP &lt;65 mm Hg, administer vasopressors to maintain MAP at ≥65 mm Hg.
+* Maintain ScvO2 &gt;70% and Hb &gt;10 g/dL
-* If MAP &gt;90 mm Hg, administer vasodilators until MAP ≤90 mm Hg.
+* Add nitroprusside / nitroglycerin / milrinone with volume loading if ScvO2 &lt;70%
-* If ScvO2 <70%, transfuse RBC to maintain Hct at ≥30%.
+* Consider levosimendan / enoximone in recalcitrant low CO syndrome
-* Once CVP/MAP/Hct are optimized, if ScvO2 is still <70%, load dobutamine 2.5 μg/kg/min.
+* ± Thyroid hormone replacement
-* Titrate dobutamine by 2.5 μg/kg/min q 30 minutes until 20 μg/kg/min or ScvO2 ≥70%.
+* ± Hydrocortisone replacement
-* Taper or discontinue dobutamine if MAP &lt;65 mm Hg or HR &gt;120 bpm.<ref>{{Cite journal| doi = 10.1056/NEJMoa010307| issn = 0028-4793| volume = 345| issue = 19| pages = 1368–1377| last1 = Rivers| first1 = E.| last2 = Nguyen| first2 = B.| last3 = Havstad| first3 = S.| last4 = Ressler| first4 = J.| last5 = Muzzin| first5 = A.| last6 = Knoblich| first6 = B.| last7 = Peterson| first7 = E.| last8 = Tomlanovich| first8 = M.| last9 = Early Goal-Directed Therapy Collaborative Group| title = Early goal-directed therapy in the treatment of severe sepsis and septic shock| journal = The New England Journal of Medicine| date = 2001-11-08| pmid = 11794169}}</ref>
+<BIG>'''For Cold Shock with Low Blood Pressure'''</BIG>
-<BIG>'''Surviving Sepsis Campaign Care Bundles'''</BIG>
 ----
-'''To Be Completed Within 3 Hours:'''
+* Titrate fluid and epinephrine
-* Measure lactate level
+* Maintain ScvO2 &gt;70% and Hb &gt;10 g/dL
-* Obtain ≥2 sets of blood cultures prior to administration of antibiotics
+* Add norepinephrine if hypotensive
-* Administer 30 mL/kg crystalloid for hypotension or lactate ≥4 mmol/L
+* Consider dobutamine / milrinone / levosimendan / enoximone if ScvO2 &lt;70%
-* Administer empiric antibiotics [[Sepsis resident survival guide#Empiric Antibiotic Therapy|(details)]]
+<BIG>'''For Warm Shock with Normal Blood Pressure'''</BIG>
-'''To Be Completed Within 6 Hours:'''
-* Administer vasopressors for persistent hypotension to maintain MAP ≥65 mm Hg
-* For septic shock or initial lactate ≥4 mmol/L (36 mg/dL):
-: — Measure CVP
-: — Measure ScvO2
-* Remeasure lactate if initial lactate was elevated
-<BIG>'''Goals of Initial Resuscitation'''</BIG>
 ----
-* CVP 8–12 mm Hg
+* Titrate fluid and norepinephrine
-* MAP ≥65 mm Hg
+* Maintain ScvO2 &gt;70%
-* Urine output ≥0.5 mL/kg/hr
+* Consider vasopressin / terripressin / angiotensin with volume if hypotensive
-* ScvO2 ≥70% or MvO2 ≥65%
+* Consider low-dose epinephrine if ScvO2 &lt;70%
-* Normalization of lactate
 </div>}}
-{{Familytree|boxstyle=width: 600px; text-align: left; font-size: 100%; padding: 0px;| | |!| | | |}}
+{{Familytree|boxstyle=width: 600px; text-align: left; font-size: 100%; padding: 0px;| |!| | | |}}
-{{Familytree|boxstyle=width: 600px; text-align: left; font-size: 100%; padding: 0px;| | C01 | | |C01=<div style="padding: 15px;">
+{{Familytree|boxstyle=width: 600px; text-align: left; font-size: 100%; padding: 0px;| A01 | | |A01=<div style="padding: 15px;">
-<BIG>'''Antimicrobial Therapy'''</BIG> [[Sepsis resident survival guide#Antimicrobial Therapy|(details)]]
+<BIG>'''For Cateocholamine Resistant Shock'''</BIG>
 ----
-* Reassess antimicrobial regimen daily for potential deescalation
+* Rule out and correct occult comorbidities
-<BIG>'''Source Control'''</BIG> [[Sepsis resident survival guide#Source Control|(details)]]
+:* Pericardial effusion
+:* Pneumothorax
+:* Hypoadrenalism
+:* Hypothyroidism
+:* Active hemorrhage
+:* Increased IAP (&gt;12 mm Hg)
+:* Necrotic tissue
+:* Inappropriate control of infection source
+:* Immunocompromised / immunosuppressive state
+* Consider PA / PiCCO / FATD catheter placement
+* Target CI 􏰃&gt;3.3 L/min/m2 and &lt;􏰁6.0 L/min/m2
+* ± Doppler ultrasound to guide fluid therapy
+* Consider ECMO
+</div>}}
+{{Familytree/end}}
+</div>
+==FIRE: Focused Initial Rapid Evaluation (Newborns)==
+<span style="background: #FFF0F5; font-weight: bold; font-style: italic;">Focused Initial Rapid Evaluation (FIRE)</span> should be undertaken to identify patients requiring urgent intervention.
+<span style="font-size: 85%;">
+'''Abbreviations''':
+CBC, complete blood count;
+CI, cardiac index;
+CK-MB, creatine kinase MB isoform;
+CVP, central venous pressure;
+DC, differential count;
+ECMO, extracorporeal membrane oxygenation;
+FATD, femoral arterial thermodilution;
+HMG, hepatomegaly;
+IAP, intra-abdominal pressure;
+ICU, intensive care unit;
+INR, international normalized ratio;
+IO, intraosseous;
+IV, intravenous;
+LFT, liver function test;
+MAP, mean arterial pressure;
+PA, pulmonary artery;
+PCWP, pulmonary capillary wedge pressure;
+PDA, patent ductus arteriosus;
+PT, prothrombin time;
+PTT, partial prothrombin time;
+SaO2, arterial oxygen saturation;
+SBP, systolic blood pressure;
+ScvO2, central venous oxygen saturation;
+SMA-7, sequential multiple analysis-7;
+SvO2, mixed venous oxygen saturation;
+VLBW, very low birth weight.
+</span>
+<div style="font-size: 90%;">
+{{Familytree/start}}
+{{Familytree|boxstyle=width: 600px; text-align: left; font-size: 100%; padding: 0px;| A01 | | |A01=<div style="padding: 15px;">
+<BIG>'''Suspected Septic Shock'''</BIG> [[Pediatric sepsis resident survival guide#Diagnostic Criteria|(details)]]
 ----
-* Remove potentially infected intravascular devices after establishing another accesss
+* Suspected infection manifested by hypothermia or hyperthermia
-<BIG>'''Infection Prevention'''</BIG> [[Sepsis resident survival guide#Infection Prevention|(details)]]
+* Inadequate tissue perfusion
+* Poor feeding
+* Diarrhea
+* Poor tone
+* Poor color
+* Tachycardia
+* Tachypnea
+* Respiratory distress
+* Maternal history of chorioamnionitis or prolonged rupture of membranes
+</div>}}
+{{Familytree|boxstyle=width: 600px; text-align: left; font-size: 100%; padding: 0px;| |!| | | |}}
+{{Familytree|boxstyle=width: 600px; text-align: left; font-size: 100%; padding: 0px;| A01 | | |A01=<div style="padding: 15px;">
+<BIG>'''The First Hour of Resuscitation'''</BIG>
 ----
-* Use oral chlorhexidine gluconate in ICU patients with severe sepsis
+* Secure airway and maintain oxygenation / ventilation
-<BIG>'''Corticosteroids'''</BIG> [[Sepsis resident survival guide#Corticosteroids|(details)]]
+* Administer IV boluses of 10 ml/kg saline until perfusion restores or HMG develops
+* Administer prostaglandin until ductal-dependent lesion is excluded
+* Administer empiric antibiotics [[Pediatric sepsis resident survival guide#Empiric Antibiotic Therapy|(details)]]
+* ± Correct hypoglycemia and hypocalcemia
+<BIG>'''For Fluid Refractory Shock'''</BIG>
 ----
-* Continuous infusion of low-dose hydrocortisone if indicated
+* Titrate dopamine 5-9 mcg/kg/min
-* Taper steroid therapy once vasopressors are no longer required
+* Administer dobutamine up to 10 mcg/kg/min
-<BIG>'''Blood Product Administration'''</BIG> [[Sepsis resident survival guide#Blood Product Administration|(details)]]
+* Consider epinephrine (0.05-0.3 􏰄g/kg/min) to restore blood pressure and perfusion
+<BIG>'''For Persistent Pulmonary Hypertension'''</BIG>
 ----
-* RBC transfusion if Hb <7.0 g/dL (target: 7.0–9.0 g/dL)
+* Administer 100% oxygen
-* Prophylactic platelets if indicated
+* Institute NaHCO3 / tromethamine until up to pH 7.50 and inhaled NO is available
-<BIG>'''Mechanical Ventilation of Sepsis-Induced ARDS'''</BIG> [[Sepsis resident survival guide#Mechanical Ventilation of Sepsis-Induced ARDS|(details)]]
+* Hyperventilate to achieve 􏰁&lt;5% difference in preductal and postductal SaO2 and 100% SaO2
+<BIG>'''Therapeutic End Points'''</BIG>
 ----
-* Tidal volume at 6 mL/kg predicted body weight
+* Normal mental status
-* Plateau pressures ≤30 cm H2O
+* Urine output 􏰃&gt;1 mL/kg/h
-* PEEP >5 cm H2O
+* Warm extremities
-* Head of the bed elevated to 30–45 degrees
+* Capillary refill 􏰉≤2 seconds
-* Prone positioning if indicated
+* Normal peripheral and central pulses
-<BIG>'''Sedation, Analgesia, and Neuromuscular blockade'''</BIG> [[Sepsis resident survival guide#Sedation, Analgesia, and Neuromuscular blockade|(details)]]
+* Normal blood pressure for age
+* Normal glucose concentration
+* Normal ionized calcium concentration
+* Difference in preductal and postductal O2 saturation 􏰁&lt;5%
+* SaO2 ≥95%
+</div>}}
+{{Familytree|boxstyle=width: 600px; text-align: left; font-size: 100%; padding: 0px;| |!| | | |}}
+{{Familytree|boxstyle=width: 600px; text-align: left; font-size: 100%; padding: 0px;| A01 | | |A01=<div style="padding: 15px;">
+<BIG>'''Beyond the First Hour of Resuscitation'''</BIG>
 ----
-* Avoid undue sedation in mechanically ventilated sepsis patients
+* ± Transfuse RBC if Hb &lt;􏰁10 g/dL
-<BIG>'''Glucose Control'''</BIG> [[Sepsis resident survival guide#Glucose Control|(details)]]
+* ± Infuse FFP if prolonged INR
+* ± Diuretics/dialysis if fluid overloaded
+* Adjust D10%-containing isotonic fluid to maintain normoglycemia
+<BIG>'''Therapeutic End Points'''</BIG>
 ----
-* Target an upper blood glucose ≤180 mg/dL
+* Normal mental status
-* Monitor q 1–2 hrs until glucose levels / insulin infusion rates are stable, then q 4 hrs thereafter
+* Urine output 􏰃&gt;1 mL/kg/h
-<BIG>'''Deep Vein Thrombosis Prophylaxis'''</BIG> [[Sepsis resident survival guide#Deep Vein Thrombosis Prophylaxis|(details)]]
+* Capillary refill 􏰉≤2 seconds
+* Warm extremities
+* Normal peripheral and central pulses
+* Normal blood pressure for age
+* CI 􏰃&gt;3.3 L/min/m2
+* SaO2 &gt;95%
+* ScvO2 &gt;􏰃70%
+* Difference in preductal and postductal O2 saturation 􏰁&lt;5%
+* Absence of right-to-left shunt, tricuspid regurgitation, or right ventricular failure
+* Normal glucose concentration
+* Normal ionized calcium concentration
+* SVC flow &gt;40 mL/kg/min
+* Normal INR
+* Normal anion gap
+* Normal lactate
+* Fluid overload &lt;10%
+</div>}}
+{{Familytree|boxstyle=width: 600px; text-align: left; font-size: 100%; padding: 0px;| |!| | | |}}
+{{Familytree|boxstyle=width: 600px; text-align: left; font-size: 100%; padding: 0px;| A01 | | |A01=<div style="padding: 15px;">
+<BIG>'''For Cold Shock with LV Dysfunction'''</BIG>
 ----
-* LMWH / dalteparin / UFH if indicated
+* Add nitroprusside / nitroglycerin / milrinone with volume loading if:
-* Compression stockings or intermittent pneumatic compression devices
+:* ScvO2 &lt;70%
-<BIG>'''Stress Ulcer Prophylaxis'''</BIG> [[Sepsis resident survival guide#Stress Ulcer Prophylaxis|(details)]]
+:* SVC flow &lt;40 mL/kg/min
+:* CI &lt;3.3 L/min/m2
+<BIG>'''For Cold Shock with Low Blood Pressure and RV Dysfunction'''</BIG>
 ----
-* H2 blocker or PPI in patients with bleeding risks
+* Administer inhaled NO if persistent pulmonary hypertension with:
-<BIG>'''Nutrition'''</BIG> [[Sepsis resident survival guide#Nutrition |(details)]]
+:* ScvO2 &lt;70%
+:* SVC flow &lt;40 mL/kg/min
+:* CI &lt;3.3 L/min/m2
+* Consider milrinone / inhaled iloprost / adenosine
+<BIG>'''For Warm Shock with Low Blood Pressure'''</BIG>
 ----
-* Administer oral or enteral feedings as tolerated within the first 48 hours
+* Titrate fluid and norepinephrine
+* Administer inotropes to maintain ScvO2 &gt;70%, SVC flow &gt;40 mL/kg/min, and CI &gt;3.3 L/min/m2
-* Administer intravenous glucose and enteral nutrition within the first 7 days
+* Consider vasopressin / terripressin / angiotensin with volume if hypotensive
-<BIG>'''Setting Goals of Care'''</BIG> [[Sepsis resident survival guide#Setting Goals of Care|(details)]]
+</div>}}
+{{Familytree|boxstyle=width: 600px; text-align: left; font-size: 100%; padding: 0px;| |!| | | |}}
+{{Familytree|boxstyle=width: 600px; text-align: left; font-size: 100%; padding: 0px;| A01 | | |A01=<div style="padding: 15px;">
+<BIG>'''For Cateocholamine Resistant Shock'''</BIG>
 ----
-* Discuss goals of care and prognosis with patients and families within 72 hours of ICU admission</div>}}
+* Rule out and correct occult comorbidities
+:* Pericardial effusion
+:* Pneumothorax
+:* Hypoadrenalism
+:* Hypothyroidism
+:* Active hemorrhage
+:* Increased IAP (&gt;12 mm Hg)
+:* Necrotic tissue
+:* Inappropriate control of infection source
+:* Immunocompromised / immunosuppressive state
+* ± Thyroid hormone replacement
+* ± Hydrocortisone replacement
+* Administer pentoxifylline if VLBW newborn
+* Consider closing PDA if hemodynamically significant
+* Consider ECMO
+</div>}}
 {{Familytree/end}}
 </div>
@@ Line 261: / Line 433: @@
 ==Empiric Antibiotic Therapy==
-===History of intravenous drug use with high prevalence of MRSA===
+===Children aged >1 month===
-{{abx|Vancomycin 1 gm IV q12h}}
+{{rx|Preferred Regimen}}
+* [[Cefotaxime]] 50 mg/kg IV q8h {{or}} [[Ceftriaxone]] 100 mg/kg IV q24h {{and}}
-===Sepsis associated with petechiae===
+* [[Vancomycin]] 15 mg/kg IV q6h
-{{abx|Ceftriaxone 2 gm IV q12h}}
+</li>
+{{rx|Alternative Regimen}}
-===Biliary source===
+* [[Aztreonam]] 7.5 mg/kg IV q6h {{and}}
-{{abx|Ampicillin-Sulbactam 3 gm IV q6h|Piperacillin-Tazobactam 3.375 gm IV q4h|Ticarcillin-Clavulanate 3.1 gm IV q4h}}
+* [[Linezolid]] 10 mg/kg IV q8h
+</li>
-===Community-acquired pneumonia===
-{{abx|Levofloxacin 750 mg IV q24h|Moxifloxacin 400 mg IV q24h}}
-AND
-{{abx|Piperacillin-Tazobactam 3.375 gm IV q4h}}
-AND
-{{abx|Vancomycin 1 gm IV q12h}}
-===Unclear infection source===
-{{abx|Doripenem 500 mg IV q8h|Ertapenem 1 gm IV q24h|Imipenem 0.5 gm IV q6h|Meropenem 1 gm IV q8h}}
-AND
-{{abx|Vancomycin 1 gm IV q12h}}
-===Low prevalence of ESBL and/or carbapenemase-producing aerobic GNB===
-{{abx|Piperacillin-Tazobactam 3.375 gm IV q4h}}
-AND
-{{abx|Vancomycin 1 gm IV q12h}}
-===High prevalence of ESBL and/or carbapenemase-producing aerobic GNB===
-{{abx|Colistin 2.5 mg/kg then 1.5 mg/kg IV q12h}}
-AND
-{{abx|Meropenem 1 gm IV q8h}}
-AND
-{{abx|Vancomycin 1 gm IV q12h}}
-==Dos==
-===Initial Resuscitation===
-* Commence protocolized, quantitative resuscitation for patients with sepsis-induced tissue hypoperfusion. Goals during the first 6 hrs of resuscitation:
-:* CVP 8–12 mm Hg
-:* MAP ≥65 mm Hg
-:* Urine output ≥0.5 mL/kg/hr
-:* ScvO2 ≥70% or MvO2 ≥65%
-* In mechanically ventilated patients or those with known preexisting decreased ventricular compliance, a higher target CVP of 12–15mm Hg should be achieved to account for the impediment in filling.
-===Diagnosis===
-* Perform routine screening for severe sepsis in potentially infected seriously ill patients to allow earlier implementation of therapy.
-* Cultures as clinically appropriate before antimicrobial therapy if no significant delay (>45 mins) in the start of antimicrobials.
-* At least 2 sets of blood cultures (both aerobic and anaerobic bottles) should be obtained before antimicrobial therapy with at least 1 drawn percutaneously and 1 drawn through each vascular access device, unless the device was recently (<48 hrs) inserted. The volume of blood drawn with the culture tube should be ≥ 10 mL.
-* The Gram stain can be useful, in particular for respiratory tract specimens, to determine if inflammatory cells are present (&gt;5 PMNs/HPF and &lt:10 squamous cells/LPF) and if culture results will be informative of lower respiratory pathogens.
-* Rapid influenza antigen testing during periods of increased influenza activity in the community is also recommended.
-* The use of the 1,3 β-d-glucan assay, mannan and anti-mannan antibody assays may be useful when suspecting invasive candidiasis.
-* Perform imaging studies promptly to confirm a potential source of infection. Diagnostic imaging may identify a source of infection that requires removal of a foreign body or drainage.
-===Antimicrobial Therapy===
-* Administration of intravenous antimicrobials within the first hour of recognition of septic shock and severe sepsis without septic shock.
-* Initial empiric anti-infective therapy of one or more drugs that have activity against all likely pathogens and that penetrate in adequate concentrations into presumed source of sepsis.
-* If treatment of candidiasis is warranted, the selection of empirical therapy (eg, an echinocandin, triazoles such as fluconazole, or amphotericin B) should be tailored to the local pattern of the most prevalent Candida species and any recent exposure to antifungal drugs.
-* Antiviral therapy should be initiated as early as possible in patients with severe sepsis or septic shock of viral origin.
-* For selected patients with severe infections associated with respiratory failure and septic shock, combination therapy with an extended spectrum beta-lactam and either an aminoglycoside or a fluoroquinolone is suggested for ''Pseudomonas aeruginosa'' bacteremia. A combination of beta-lactam and a macrolide is suggested for patients with septic shock from ''Streptococcus pneumoniae'' bacteremia.
-* The duration of therapy should typically be limited to 7–10 days if clinically indicated. Longer courses may be appropriate in patients who have a slow clinical response, undrainable foci of infection, ''Staphylococcus aureus'' bacteremia; some fungal and viral infections, or immunologic deficiencies including neutropenia.
-* Antimicrobial regimen should be reassessed daily for potential deescalation.
-===Source Control===
-* A specific anatomical diagnosis of infection requiring consideration for emergent source control should be sought and diagnosed or excluded as rapidly as possible.
-* Control infection source within the first 12 hours after the diagnosis is made.
-* Intervention associated with the least physiologic insult should be used (eg, percutaneous rather than surgical drainage of an abscess).
-* If intravascular access devices are a possible source of severe sepsis or septic shock, they should be removed promptly after other vascular access has been established.
-* If infected peripancreatic necrosis is a potential infection source, definitive intervention should be delayed until adequate demarcation of viable and nonviable tissues has occurred.
-===Infection Prevention===
-* Oral chlorhexidine gluconate should be used as a form of oropharyngeal decontamination to reduce the risk of VAP in ICU patients with severe sepsis.
-===Fluid Therapy of Severe Sepsis===
-* Use crystalloids as the initial fluid of choice in the resuscitation of severe sepsis and septic shock.
-* Initial fluid challenge in patients with sepsis-induced tissue hypoperfusion with suspicion of hypovolemia to achieve a minimum of 30 mL/kg of crystalloids.
-===Vasopressors===
-* Initiate vasopressor therapy (norepinephrine as the first choice) to target a mean arterial pressure of 65 mm Hg.
-* Consider epinephrine when an additional agent is required to maintain adequate blood pressure. Vasopressin may be added to norepinephrine with intent of either raising MAP or decreasing norepinephrine dosage.
-* Phenylephrine is not recommended in the treatment of septic shock <u>except</u>:
-:* Norepinephrine is associated with serious arrhythmias
-:* Cardiac output is known to be high and blood pressure persistently low
-:* As salvage therapy when combined inotrope/vasopressor drugs and low dose vasopressin have failed to achieve MAP target
-===Inotropic Therapy===
-* A trial of dobutamine infusion up to 20 micrograms/kg/min can be administered or added to vasopressor in the presence of:
-:* Myocardial dysfunction as suggested by elevated cardiac filling pressures and low cardiac output
-:* Ongoing signs of hypoperfusion, despite achieving adequate intravascular volume and adequate MAP
-* Cardiac index should be maintained at predetermined supranormal levels.
-===Corticosteroids===
+===Children aged <1 month===
-* Steroids may be indicated in the presence of a history of steroid therapy or adrenal dysfunction.
+{{rx|Preferred Regime}}
-* When low-dose hydrocortisone is administered, continuous infusion rather than repetitive bolus injections should be used.
+* [[Ampicillin]] 25 mg/kg IV q8h {{and}}
+* [[Cefotaxime]] 50 mg/kg q12h {{and}}
+* [[Vancomycin]] 15 mg/kg IV q12h (if suspecting [[MRSA]])
+</li>
+{{rx|Alternative Regimen}}
+* [[Ampicillin]] 25 mg/kg IV q6h {{and}}
+* [[Ceftriaxone]] 75 mg/kg IV q24h {{and}}
+* [[Vancomycin]] 15 mg/kg IV q12h (if suspecting [[MRSA]])
+</li>
-* Steroid therapy should be tapered when vasopressors are no longer required.
+==Dos and Don'ts==
+====<span style="background: #FFFFF0;">Initial Resuscitation</span>====
+* For respiratory distress and hypoxemia, start with face mask oxygen or if needed and available, high flow nasal cannula oxygen or nasopharyngeal CPAP (NP CPAP). For improved circulation, peripheral intravenous access or intraosseus access can be used for fluid resuscitation and inotrope infusion when a central line is not available. If mechanical ventilation is required then cardiovascular instability during intubation is less likely after appropriate cardiovascular resuscitation. {{GRADE2|C}}
-===Blood Product Administration===
+* Initial therapeutic end points of resuscitation of septic shock: capillary refill of ≤2 secs, normal blood pressure for age, normal pulses with no differential between peripheral and central pulses, warm extremities, urine output >1 mL·kg-1·hr-1, and normal mental status. Scvo2 saturation ≥70% and cardiac index between 3.3 and 6.0 L/min/m2 should be targeted thereafter. {{GRADE2|C}}
-* Once tissue hypoperfusion has resolved and in the absence of extenuating circumstances, RBC transfusion should be considered when Hb <7.0 g/dL to target a concentration of 7.0–9.0 g/dL in adults.
-* In patients with severe sepsis, administer prophylactic platelets when:
-:* PLT <10,000/mm3 (10 x 10<sup>9</sup>/L) in the absence of apparent bleeding
-:* PLT <20,000/mm3 (20 x 10<sup>9</sup>/L) in the presence of bleeding risks
-:* PLT ≥50,000/mm3 (50 x 10<sup>9</sup>/L) for active bleeding, surgery, or invasive procedures
-===Mechanical Ventilation of Sepsis-Induced ARDS===
+* Follow American College of Critical Care Medicine-Pediatric Life Support (ACCM-PALS) guidelines for the management of septic shock. {{GRADE1|C}}
-* Target a tidal volume of 6mL/kg predicted body weight in patients with sepsis-induced ARDS.
-* Measure plateau pressures in patients with ARDS. Initial upper limit for plateau pressures in a passively inflated lung should be ≤30 cm H2O.
-* Positive end-expiratory pressure (PEEP) should be applied to avoid alveolar collapse at end expiration. A PEEP >5 cm H2O is usually required to avoid lung collapse.
-* Higher rather than lower levels of PEEP should be used for patients with sepsis-induced moderate to severe ARDS. Strategies to titrate PEEP include:
-:* Titrate PEEP and tidal volume according to bedside measurements of thoracopulmonary compliance with the objective of obtaining the best compliance.
-:* Titrate PEEP based on severity of oxygenation deficit and guided by the FiO2 required to maintain adequate oxygenation.
-* Mechanically ventilated sepsis patients should be maintained with the head of the bed elevated to 30–45 degrees to limit aspiration risk and to prevent the development of ventilator-associated pneumonia.
-* Mechanically ventilated patients with severe sepsis should undergo spontaneous breathing trials regularly to evaluate the ability to discontinue mechanical ventilation when they satisfy the following criteria:
-:* Arousable
-:* Hemodynamically stable without vasopressor agents
-:* No new potentially serious conditions
-:* Low ventilatory and end-expiratory pressure requirements
-:* Low FiO2 requirements which can be met safely delivered with a face mask or nasal cannula.
-* Prone positioning may be considered in sepsis-induced ARDS patients with a PaO2/FiO2 ratio ≤100 mm Hg.
-* Undertake a conservative rather than liberal fluid strategy for patients with established sepsis-induced ARDS who do not have evidence of tissue hypoperfusion.
-===Sedation, Analgesia, and Neuromuscular blockade in Sepsis===
+* Evaluate for and reverse pneumothorax, pericardial tamponade, or endocrine emergencies in patients with refractory shock. {{GRADE1|C}}
-* Continuous or intermittent sedation should be minimized in mechanically ventilated sepsis patients, targeting specific titration endpoints.
-* If neuromuscular blocking agents must be maintained, either intermittent bolus as required or continuous infusion with train-of-four monitoring of the depth of blockade should be used.
-* A short course of NMBA of not greater than 48 hours may be considered for patients with early sepsis-induced ARDS and a PaO2/FiO2 of &lt;150 mm Hg.
-===Glucose Control===
+====<span style="background: #FFFFF0;">Antibiotics and Source Control</span>====
-* A protocolized approach should be undertaken for ICU patients with severe sepsis when 2 consecutive blood glucose levels are &gt;180 mg/dL. This protocolized approach should target an upper blood glucose ≤180 mg/dL rather than an upper target blood glucose ≤ 110 mg/dL.
+* Empiric antibiotics be administered within 1 hr of the identification of severe sepsis. Blood cultures should be obtained before administering antibiotics when possible but this should not delay administration of antibiotics. The empiric drug choice should be changed as epidemic and endemic ecologies dictate (eg H1N1, MRSA, chloroquine resistant malaria, penicillin-resistant pneumococci, recent ICU stay, neutropenia). {{GRADE1|D}}
-* Blood glucose values should be monitored every 1–2 hrs until glucose values and insulin infusion rates are stable and then every 4 hrs thereafter
-===Renal Replacement Therapy===
+* Clindamycin and anti-toxin therapies for toxic shock syndromes with refractory hypotension. {{GRADE2|D}}
-* Either continuous renal replacement therapy or intermittent hemodialysis may be used in patients with severe sepsis and acute renal failure.
-* Continuous therapies may be considered to facilitate management of fluid balance in hemodynamically unstable septic patients.
-===Deep Vein Thrombosis Prophylaxis===
+* Early and aggressive source control. {{GRADE1|D}}
-* Patients with severe sepsis should receive daily prophylaxis against venous thromboembolism (VTE).
-* VTE prophylaxis should be accomplished with daily subcutaneous low-molecular weight heparin (LMWH). If creatinine clearance is <30 mL/min, use dalteparin or another form of LMWH that has a low degree of renal metabolism or UFH.
-* Patients with severe sepsis should  be treated with a combination of pharmacologic therapy and intermittent pneumatic compression devices whenever possible.
-* Septic patients who have a contraindication for heparin use (eg, thrombocytopenia, severe coagulopathy, active bleeding, recent intracerebral hemorrhage) should not receive prophylaxis, but receive mechanical prophylactic treatment, such as compression stockings or intermittent compression devices, unless contraindicated.
-===Stress Ulcer Prophylaxis===
+* Clostridium difficile colitis should be treated with enteral antibiotics if tolerated. Oral vancomycin is preferred for severe disease. {{GRADE1|A}}
-* Stress ulcer prophylaxis using H2 blocker or proton pump inhibitor should be given to patients with severe sepsis/septic shock who have bleeding risk factors.
-* When stress ulcer prophylaxis is used, use proton pump inhibitors rather than H2 blockers.
-===Nutrition===
+====<span style="background: #FFFFF0;">Fluid Resuscitation</span>====
-* Administer oral or enteral feedings as tolerated, rather than either complete fasting or only intravenous glucose within the first 48 hours after a diagnosis of severe sepsis/septic shock.
+* In the industrialized world with access to inotropes and mechanical ventilation, initial resuscitation of hypovolemic shock begins with infusion of isotonic crystalloids or albumin with boluses of up to 20 mL/kg crystalloids (or albumin equivalent) over 5–10 minutes, titrated to reversing hypotension, increasing urine output, and attaining normal capillary refill, peripheral pulses, and level of consciousness without inducing hepatomegaly or rales. If hepatomegaly or rales exist then inotropic support should be implemented, not fluid resuscitation. In non-hypotensive children with severe hemolytic anemia (severe malaria or sickle cell crises) blood transfusion is considered superior to crystalloid or albumin bolusing. {{GRADE2|C}}
-* Use intravenous glucose and enteral nutrition rather than total parenteral nutrition alone or parenteral nutrition in conjunction with enteral feeding in the first 7 days after a diagnosis of severe sepsis/septic shock.
-* Use nutrition with no specific immunomodulating supplementation rather than nutrition providing specific immunomodulating supplementation in patients with severe sepsis.
-===Setting Goals of Care===
+====<span style="background: #FFFFF0;">Inotropes/Vasopressors/Vasodilators</span>====
-* Discuss goals of care and prognosis with patients and families.
+* Begin peripheral inotropic support until central venous access can be attained in children who are not responsive to fluid resuscitation. {{GRADE2|C}}
-* Incorporate goals of care into treatment and end-of-life care planning, utilizing palliative care principles where appropriate.
-* Address goals of care as early as feasible, but no later than within 72 hours of ICU admission.
-==Don'ts==
+* Patients with low cardiac output and elevated systemic vascular resistance states with normal blood pressure be given vasodilator therapies in addition to inotropes. {{GRADE2|C}}
-===Antimicrobial Therapy===
+====<span style="background: #FFFFF0;">Extracorporeal Membrane Oxygenation (ECMO)</span>====
-* Empiric combination therapy should not be used for more than 3–5 days. De-escalation to the most appropriate monotherapy should be performed as soon as the susceptibility profile is ascertained.
+* Consider ECMO for refractory pediatric septic shock and respiratory failure. {{GRADE2|C}}
-* Antimicrobial agents should not be used in patients with severe inflammatory states determined to be of noninfectious cause.
-===Fluid Therapy of Severe Sepsis===
+====<span style="background: #FFFFF0;">Corticosteroids</span>====
-*  Do not use hydroxyethyl starches for fluid therapy resuscitation of severe sepsis and septic shock.
+* Timely hydrocortisone therapy in children with fluid refractory, catecholamine resistant shock and suspected or proven absolute (classic) adrenal insufficiency. {{GRADE1|A}}
-===Vasopressors===
+====<span style="background: #FFFFF0;">Blood Products and Plasma Therapies</span>====
-* Do not use low dose vasopressin as the single vasopressor.
+* Similar hemoglobin targets in children as in adults. During resuscitation of low superior vena cava oxygen saturation shock (< 70%), hemoglobin levels of 10 g/dL are targeted. After stabilization and recovery from shock and hypoxemia then a lower target > 7.0 g/dL can be considered reasonable. {{GRADE1|B}}
-* Do not use low-dose dopamine for renal protection.
-===Corticosteroids===
+* Similar platelet transfusion targets in children as in adults. {{GRADE2|C}}
-* Do not administer corticosteroids for the treatment of sepsis in the absence of shock.
-* Do not use intravenous hydrocortisone to treat adult septic shock patients if adequate fluid resuscitation and vasopressor therapy are able to restore hemodynamic stability.
-* ACTH stimulation test is not recommended for identifying adults with septic shock who should receive hydrocortisone.
-===Blood Product Administration===
+* Use plasma therapies in children to correct sepsis-induced thrombotic purpura disorders, including progressive disseminated intravascular coagulation, secondary thrombotic microangiopathy, and thrombotic thrombocytopenic purpura. {{GRADE2|C}}
-* Do not use erythropoietin as a specific treatment of anemia associated with severe sepsis.
-* Do not use fresh frozen plasma to correct laboratory clotting abnormalities in the absence of bleeding or planned invasive procedure.
-===Immunoglobulins and Selenium===
+====<span style="background: #FFFFF0;">Mechanical Ventilation</span>====
-* Do not use intravenous immunoglobulins in adult patients with severe sepsis or septic shock.
+* Lung-protective strategies during mechanical ventilation. {{GRADE2|C}}
-* Do not use intravenous selenium for the treatment of severe sepsis.
-===Mechanical Ventilation of Sepsis-Induced ARDS===
+====<span style="background: #FFFFF0;">Sedation/Analgesia/Drug Toxicities</span>====
-* Do not routinely place the pulmonary artery catheter for patients with sepsis-induced ARDS.
+* We recommend use of sedation with a sedation goal in critically ill mechanically ventilated patients with sepsis. {{GRADE1|D}}
-* Do not use beta 2-agonists for treatment of sepsis-induced ARDS in the absence of specific indications such as bronchospasm.
-===Sedation, Analgesia, and Neuromuscular blockade in Sepsis===
+* Monitor drug toxicity labs because drug metabolism is reduced during severe sepsis, putting children at greater risk of adverse drug-related events. {{GRADE1|C}}
-* Neuromuscular blocking agents (NMBAs) should be avoided if possible in the septic patient without ARDS due to the risk of prolonged neuromuscular blockade following discontinuation.
-===Bicarbonate Therapy===
+====<span style="background: #FFFFF0;">Glycemic Control</span>====
-* Sodium bicarbonate should not be used for the purpose of improving hemodynamics or reducing vasopressor requirements in patients with hypoperfusion-induced lactic acidemia with pH ≥7.15.
+* Control hyperglycemia using a similar target as in adults ≤ 180 mg/dL. Glucose infusion should accompany insulin therapy in newborns and children because some hyperglycemic children make no insulin whereas others are insulin resistant. {{GRADE2|C}}
-===Stress Ulcer Prophylaxis===
+====<span style="background: #FFFFF0;">Diuretics and Renal Replacement Therapy</span>====
-* Patients without risk factors should not receive stress ulcer prophylaxis.
+* Use diuretics to reverse fluid overload when shock has resolved, and if unsuccessful then continuous venovenous hemofiltration (CVVH) or intermittent dialysis to prevent > 10% total body weight fluid overload. {{GRADE2|C}}
-===Nutrition===
+====<span style="background: #FFFFF0;">Nutrition</span>====
-* Avoid mandatory full caloric feeding in the first week but rather suggest low dose feeding (eg, up to 500 calories per day), advancing only as tolerated.
+* Enteral nutrition given to children who can be fed enterally, and parenteral feeding in those who cannot. {{GRADE2|C}}
 ==References==
 {{Reflist|2}}
+</div></div>
 [[Category:Resident survival guide]]