II. Signs

  1. Fever or Hypothermia
    1. Temperature > 101.3 F (38.5 C)
    2. Temperature < 96.8 F (36.0 C)
    3. Contrast with adult fever definition of >100.4 (38.0 C)
  2. Tachycardia
    1. See Heart Rate for age-based normal range
  3. Tachypnea
    1. See Respiratory Rate for age-based normal range
  4. Peripheral Vasoconstriction (cold, pale extremities)
    1. Most children under age 12 years with Septic Shock will compensate with marked increase in SVR (cold shock)
  5. Hypotension
    1. Ominous, late sign preceding imminent cardiovascular collapse
    2. Systolic Blood Pressure is typically maintained >70 mmHg + (2 * age) with very high systemic vascular resistance
  6. Abnormal appearance
    1. Irritability
    2. Increased crying
    3. Lethargy
  7. Increased or decreased sleep
  8. Decreased feeding
  9. Petechiae or Purpura

IV. Labs

  1. Blood Cultures
  2. Urinalysis
  3. Lumbar Puncture
  4. Complete Blood Count
    1. Neither sensitive nor specific to adequately rule-in or rule-out serious infection
  5. Acute phase reactants and bacterial infection markers
    1. Insufficiently sensitive to exclude serious infection (decision to perform LP should not be based on these markers)
    2. C-Reactive Protein (CRP)
    3. Procalcitonin

V. Imaging

VI. Types

  1. Warm Shock
    1. Accounts for 20% of children under age 12 years (esp. if indwelling lines), most adults and teens over age 12 years
    2. High or normal Cardiac Output (CO)
    3. Low systemic vascular resistance (SVR)
  2. Cold Shock
    1. Accounts for 80% of children under age 12 years
    2. Low Cardiac Output (CO)
    3. Systemic vascular resistance (SVR)
      1. Increased SVR (60% of children)
      2. Decreased SVR (20% of children)

VII. Diagnosis

  1. Sepsis
    1. Systemic Inflammatory Response Syndrome (SIRS) and
    2. Suspected or proven infection
  2. Severe Sepsis
    1. Sepsis and
    2. Organ dysfunction (one of the following)
      1. Cardiovascular organ dysfunction (see criteria below) or
      2. Acute Respiratory Distress Syndrome (ARDS) or
      3. Two or more organ dysfunctions (see criteria below)
  3. Septic Shock
    1. Sepsis and
    2. Cardiovascular organ dysfunction (see criteria below)
  4. Organ Dysfunction criteria
    1. Cardiovascular dysfunction
      1. Dysfunction despite NS or LR fluid bolus >40 ml/kg in 1 hour
      2. Criteria (requires 1 for diagnosis)
        1. Systolic Blood Pressure <2 SD below normal for age or <5th percentile or
        2. Pressors required to maintain adequate Blood Pressure
          1. Dopamine >5 mcg/kg or
          2. Dobutamine, Epinephrine or Norepinephrine
        3. Two of the following
          1. Metabolic Acidosis (Base Deficit >5.0 mEq/L) without other explanation
          2. Arterial Lactic Acid >2 times the upper normal limit
          3. Oliguria (urine output <0.5 ml/kg/h)
          4. Prolonged Capillary Refill >5 seconds
          5. Difference between core Temperature and peripheral Temperature >3 C (5.4 F)
    2. Respiratory dysfunction
      1. PaO2 per FIO2 <300 mmHg (not due to cyanotic heart disease or preexisting lung disease) or
      2. PaCO2 >65 or 20 mmHg over baseline PaCO2 or
      3. FIO2 >0.5 required to maintain Oxygen Saturation >92% or
      4. Mechanical Ventilation required non-electively (invasive or noninvasive)
    3. Neurologic dysfunction
      1. Glasgow Coma Scale: 11 or less or
      2. Acute change in mental status with a fall in GCS 3 points or more from an abnormal baseline
    4. Hematologic dysfunction
      1. Platelet Count <80k mm3 or
      2. Platelet Count with 50% decline in Platelet Count from highest recorded value in the last 3 days (chronic hematology, oncology patients) or
      3. INR >2
    5. Renal dysfunction
      1. Serum Creatinine >2 times normal for age or 2 fold increase over baseline Serum Creatinine
    6. Hepatic dysfunction
      1. Total Serum Bilirubin >4 mg/dl (not newborn Bilirubin) or
      2. Serum ALT >2 times normal for age

VIII. Management

  1. Precautions
    1. Do not be satisfied with a normal Blood Pressure (in the face of other signs of poor perfusion)
      1. Blood Pressure is frequently normal in children despite severe Sepsis and cardiac dysfunction
        1. Children under age 12 years typically maintain Blood Pressure by increasing systemic vascular resistance (SVR)
        2. However, children cannot significantly increase Cardiac Output, and a Blood Pressure fall is an ominous sign
      2. Manage based on signs of poor perfusion despite a normal Blood Pressure (see below)
      3. Start with aggressive hydration (20 cc/kg boluses up to 60 cc/kg cummulatively) and move rapidly to pressors if indicated
    2. Lab markers are not sufficient to exclude serious infection
      1. Decision to perform complete evaluation including LP with aggressive management is based on overall clinical assessment
    3. Monitor closely with frequent re-evaluation after each intervention until stable
    4. Do not delay pressors when indicated for central access
      1. Administer pressors for up to 4 hours until central access is available
      2. Risk of extravasation is outweighed by the risk of overall worse outcome
      3. Central access is more difficult and time consuming to obtain in children and often requires Sedation
  2. Target goals for interventions: Counteract markers of poor perfusion
    1. Tachycardia
    2. Lactic Acid >4 mg/dl
    3. SVO2 <70%
    4. Poor Capillary Refill
    5. Lethargy or poor responsiveness
    6. Avoid Blood Pressure as a marker of adequate perfusion (typically misleadingly normal in children)
      1. However, a fall in Blood Pressure is an ominous sign and requires aggressive management
      2. Age 0 to 3 months old: Maintain mean arterial pressure (MAP) > Gestational age + weeks of life
      3. Age 3 to 12 months old: Maintain systolic Blood Pressure > 70 mmHg
      4. Age >1 year old: Maintain systolic Blood Pressure >70 mmHg + (2 * age)
  3. Step 1: Immediate
    1. Provide high flow Supplemental Oxygen
    2. Obtain intravenous or Intraosseous Access within 5-10 minutes
    3. Obtain initial lab studies including Blood Culture
  4. Step 2: Initial Resuscitation
    1. NS or LR 20 cc/kg bolus, repeated up to 60 ml/kg until response or Fluid Overload
      1. Ongoing evaluation for Fluid Overload by Ultrasound (e.g. RUSH Exam, IVC Ultrasound for Volume Status)
      2. Ongoing evaluation for Fluid Overload by examination (e.g. pulmonary rales or Hepatomegaly)
    2. Correct Glucose and calcium
      1. Correct Hypoglycemia
      2. Correct Hypocalcemia
    3. Administer brioad-spectrum empiric antibiotics early (associated with best outcomes)
    4. Order first line Vasopressor to be available at bedside (see agent selection under Step 3)
  5. Step 3: Fluid resistant shock management
    1. Determine if fluid resistant shock within the first 15-30 minutes
    2. Obtain central Intravenous Access when able (but do not delay pressors in refractory shock)
      1. See precautions above
      2. Start Vasopressors via peripheral access (or IO may be used, but less ideal)
    3. Start inotrope (Catecholamine) and titrate to signs of improved perfusion (see above)
      1. Cold shock (most children under age 12 years)
        1. Agent 1: Dopamine (preferred pressor in children)
          1. Start Dopamine 5 mcg/kg/min
          2. Titrate Domamine to 10 mcg/kg/min
        2. Agent 2: Epinephrine (add to Dopamine if refractory)
      2. Warm shock (most teens and adults)
        1. Agent 1: Norepinephrine (preferred pressor in age over 12 years old)
        2. Agent 2: Vasopressin (or consider Terlipressin, Angiotensin)
    4. Consider intubation
  6. Step 4: Inotrope (Catecholamine) resistant shock management
    1. Consider Hydrocortisone IV for Adrenal Insufficiency
    2. Central monitoring directs next step
      1. Central Venous Pressure
      2. Mean arterial pressure
      3. SVO2 (>70% is goal)
      4. Rapid Ultrasound in Shock (RUSH Exam)
  7. Step 5: Central monitoring directed management
    1. See shock type definitions above (warm and cold shock)
    2. Goal SvO2 >70% (Hemoglobin >10g/dl)
    3. Cold shock with normal Blood Pressure
      1. First: Titrate crystalloid, Dopamine and Epinephrine to goal SvO2 >70%
      2. Next: Add Vasodilator if SvO2 <70% (e.g. Milrinone, a Phosphodiesterase Inhibitor)
        1. Do not add Milrinone until Blood Pressure and perfusion are improved
        2. Prematurely starting Milrinone with its potent vasodilation and long half-life can worsen perfusion that is difficult to counter
    4. Cold shock with low Blood Pressure
      1. First: Titrate crystalloid, Dopamine and Epinephrine to goal SvO2 >70%
      2. Next: If persistent Hypotension, consider adding norepinephine
      3. Next: Add Vasodilator if SvO2 <70% (e.g. Milrinone, Dobutamine) if Blood Pressure corrects
        1. See precautions above regarding not starting vasodilators prematurely
    5. Warm shock with low Blood Pressure
      1. First: Titrate crystalloid, Norepinephrine to goal SvO2 >70%
      2. Next: If persistent Hypotension, consider adding vasopressin, Terlipressin, Angiotensin
      3. Next: Consider low dose Epinephrine

IX. References

  1. Claudius and Melendez in Herbert (2014) EM:Rap 14(7): 6-8
  2. Fuchs and Yamamoto (2011) APLS, Jones and Bartlett, p. 104-13
  3. Orman and Sloas in Herbert (2014) EM:Rap 14(11): 6-7
  4. Brierly (2009) Crit Care Med 37: 666-88 [PubMed]
  5. Goldstein (2005) Pediatr Crit Care Med 6:2-8 [PubMed]

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Ontology: Septicemia (C0036690)

Definition (MSHCZE) Dř. tak byl označován stav, při němž v krvi dochází k rozsevu bakterií ve shlucích, které se obv. uvolňují z infikované krevní sraženiny (trombu při hnisavém zánětu žil či endokarditidě) a embolizací mohou vést k septickému infarktu a dalšímu šíření infekce do jiných orgánů. Též septikopyemie, pyemie. Dnes ztotožňováno s pojmem sepse. (cit. Velký lékařský slovník online, 2013 http://lekarske.slovniky.cz/ )
Definition (NCI_CTCAE) A disorder characterized by the presence of pathogenic microorganisms in the blood stream that cause a rapidly progressing systemic reaction that may lead to shock.
Definition (NCI_NCI-GLOSS) Disease caused by the spread of bacteria and their toxins in the bloodstream.
Definition (NCI) The presence of pathogenic microorganisms in the blood stream causing a rapidly progressing systemic reaction that may lead to shock. Symptoms include fever, chills, tachycardia, and increased respiratory rate. It is a medical emergency that requires urgent medical attention.
Definition (CSP) systemic disease associated with presence and persistance of pathogenic microorganisms or their toxins in the blood.
Definition (MSH) Systemic disease associated with the presence of pathogenic microorganisms or their toxins in the blood.
Concepts Disease or Syndrome (T047)
MSH D018805
ICD9 038.9, 038
ICD10 A41.9
SnomedCT 187333004, 266089004, 186392004, 40555009, 154313001, 105592009, 91302008
LNC MTHU020833
English Unspecified septicemia, SEPTICAEMIA, SEPTICEMIA, Septicaemia, Septicaemia NOS, Septicaemia, unspecified, Septicemia, unspecified, [X]Septicaemia, unspecified, [X]Septicemia, unspecified, Blood Poisoning, Poisoning, Blood, Septicemia NOS, POIS BLOOD, BLOOD POIS, septicemia (diagnosis), septicemia, Poisonings, Blood, Blood Poisonings, Septicemias, Septicemia [Disease/Finding], Blood poisoning, poisoning blood, blood poisoning, septicaemia, [X]Septicemia, unspecified (disorder), Septicaemia (disorder), (Septicaemia NOS) or (sepsis) (disorder), (Septicaemia NOS) or (sepsis), (Septicemia NOS) or (sepsis), Septicemia NOS (disorder), Septicemia (disorder), sepsis, SEPSIS, toxemia, Sepsis Syndrome, Unspecified septicaemia, Septicemia, intoxication; septic, general, intoxication; septic, septic; intoxication, general, septic; intoxication, Blood poisoning, NOS, Septicemia, NOS, Septicaemia, NOS, Sepsis
French SEPTICEMIE, Septicémie SAI, Septicémie non précisée, Septicémie
Portuguese SEPTICEMIA, Septicemia NE, Septicémia NE, Septicemia não especificada, Septicemia
Spanish SEPTICEMIA, Septicemia NEOM, Septicemia, Septicemia por organismo indeterminado, Septicemia no especificada, [X]septicemia, no especificada, septicemia, SAI, [X]septicemia, no especificada (trastorno), septicemia, SAI (trastorno), septicemia, septicemia (trastorno)
German SEPTIKAEMIE, unspezifische Septikaemie, Septikaemie NNB, Septikaemie ohne weitere Angabe, Septikämie, Sepsis, nicht naeher bezeichnet, Septhämie, Septisches Fieber, Septikaemie, Septikhämie, Septikhaemie
Dutch septikemie, septikemie NAO, niet-gespecificeerde septikemie, intoxicatie; septisch, gegeneraliseerd, intoxicatie; septisch, septisch; intoxicatie, gegeneraliseerd, septisch; intoxicatie, Sepsis, niet gespecificeerd
Italian Setticemia NAS, Setticemia non specificata, Setticemia
Japanese 敗血症, 敗血症NOS, 詳細不明の敗血症, ハイケツショウ, ショウサイフメイノハイケツショウ, ハイケツショウNOS
Czech septikémie, Septikemie, Septikemie NOS, Blíže neurčená septikemie, otrava krve, septikemie
Korean 상세불명의 패혈증
Hungarian septicaemia, nem meghatározott septicaemia, nem meghatározott szeptikémia, septicaemia k.m.n.
Norwegian Blodforgiftning, Septikemi

Ontology: Septic Shock (C0036983)

Definition (NCI) A state of acute circulatory failure characterized by persistent arterial hypotension despite adequate fluid resuscitation or by tissue hypoperfusion unexplained by other causes.(NICHD)
Definition (CSP) shock caused by infection; frequently caused by gram negative bacteria, although some cases have been caused by other bacteria, viruses, fungi, and protozoa; characterized by fever, chills, tachycardia, tachypnea, and hypotension.
Definition (MSH) Sepsis associated with HYPOTENSION or hypoperfusion despite adequate fluid resuscitation. Perfusion abnormalities may include, but are not limited to LACTIC ACIDOSIS; OLIGURIA; or acute alteration in mental status.
Concepts Pathologic Function (T046)
MSH D012772
ICD9 785.52
SnomedCT 207031008, 158359009, 76571007
English Shock, Septic, [D]Septic shock, [D]Septicaemic shock, [D]Septicemic shock, [D]Septic shock (context-dependent category), SHOCK SEPTIC, septic shock (diagnosis), septic shock, Shock septic, Shock, Septic [Disease/Finding], septicemic shock, [D]Septic shock (situation), SEPTIC SHOCK, SHOCK, SEPTIC, Septic shock, Septicaemic shock, Septicemic shock, Sepsis-associated hypotension, Septic shock (disorder), Septic Shock, septic; shock, shock; septic
Dutch shock septisch, septisch; shock, shock; septisch, septische shock, Septische shock, Shock, septische
German Schock septisch, Septischer Schock, Schock, septischer
Swedish Chock, septisk
Spanish [D]choque séptico (categoría dependiente del contexto), choque septicémico, Shock Séptico, Choque Séptico, [D]choque séptico, [D]shock séptico, [D]choque séptico (situación), Síndrome de Shock Tóxico, Síndrome de Choque Tóxico, Shock Tóxico, Síndrome del Shock Tóxico, Shock Endotóxico, Shock séptico, choque septicémico (trastorno), shock septicémico, choque séptico (trastorno), choque séptico, shock séptico
Japanese ハイケツショウセイショック, ショック-中毒性, 中毒性ショック, 内毒素ショック, 中毒性ショック症候群, ショック-内毒素, 敗血症性ショック, 敗血性ショック, ショック-エンドトキシン, 細菌性ショック, 感染性ショック, エンドトキシンショック, ショック-敗血症性
Finnish Septinen sokki
Czech Septický šok, septický šok, šok septický
Polish Wstrząs septyczny, Wstrząs endotoksyczny
Hungarian septicus shock, Septicus shock
Norwegian Sjokk, septisk, Septisk sjokk
Portuguese Choque séptico, Choque Séptico
French Choc septique
Italian Shock settico