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Sepsis, Emergency Medicine

Basics

Description

- Sepsis = infection with ≥2 SIRS criteria: - Release of chemical messengers by the inflammatory response - Macrocirculatory failure through decreased cardiac output or decreased perfusion pressure - Microcirculatory failure through impaired vascular autoregulatory mechanisms and functional shunting of oxygen - Cytopathic hypoxia and mitochondrial dysfunction

- Hemodynamic changes result from the inflammatory response: - Elevated cardiac output in response to vasodilatation - Later myocardial depression:

- Sepsis should be viewed as a continuum of severity from a proinflammatory response to organ dysfunction and tissue hypoperfusion: - Severe sepsis: Sepsis with at least 1 of the following organ dysfunctions: - Acidosis - Renal dysfunction - Acute change in mental status - Pulmonary dysfunction - Hypotension - Thrombocytopenia or coagulopathy - Liver dysfunction

- Gram-negative bacteria most common: - Escherichia coli - Pseudomonas aeruginosa - Rickettsiae - Legionella spp.

- Children with a minor infection may have many of the findings of SIRS. - Major causes of pediatric bacterial sepsis: - Neisseria meningitidis - Streptococcal pneumonia - Haemophilus influenzae

- Question for signs of infection and a systemic inflammatory response: - Fever - Dyspnea - Altered mental status: - Change in mental status - Confusion - Delirium

- Look for a source of the infection: - Cough, shortness of breath - Abdominal pain - Diarrhea - Dysuria/frequency

- An elevated respiratory rate is an early warning sign of sepsis and occurs without underlying pulmonary pathology or acidosis. - BP is often normal early in sepsis. - Hypotension when septic shock occurs - Extremities are often warmed and flushed despite hypotension. - Look for a source of the infection: - Abdominal exam - Rectal exam to assess for an abscess - Chest exam for signs of pneumonia - Any rash is important: - Localized erythema with lymphangitis (streptococcal or staphylococcal cellulitis) - Rash involving palms of hands and soles of feet (rickettsial infection) - Petechiae scattered on the torso and extremities (meningococcemia) - Ecthyma gangrenosum (pseudomonas septicemia) - Round, indurated, painless lesion with surrounding erythema and central necrotic black eschar

- Decubitus ulcers - Indwelling catheter:

- CNS infections: - Coma - Neck stiffness (meningitis)

- CBC with differential: - Leukocytosis is insensitive and nonspecific - Neutrophil count <500 cells/mm3 should prompt isolation and empiric IV antibiotics in chemotherapy patients. - >5% bands on a peripheral smear is an imperfect indicator of infection. - Hematocrit: - Patients should be maintained with a hematocrit >30% and hemoglobin >10 g/dL.

- Imaging studies to locate the source of the infection based on the presentation: - CT scan of the abdomen and pelvis - Abdominal US for gallbladder disease - Transthoracic or transesophageal echocardiogram

- Early goal-directed therapy: - 500 cc boluses of 0.9% saline up to 1 " 2 L empirically - Place central line. - Continue 500 cc saline boluses until CVP >8 cm H2O. - If the mean arterial pressure <65 mm Hg and CVP >8, then initiate pressors: - Norepinephrine or dopamine to raise BP - Norepinephrine is preferred if tachycardia or dysrhythmias are present. - Epinephrine for cases where shock is refractory to other pressors - If the ScvO2 <70 and HCT <30, transfuse 2 U PRBCs. - If ScvO2 >70 and HCT >30 and MAP >60, then add dobutamine.

  • Presence of an infection with an associated systemic inflammatory response
  • The systemic inflammatory response syndrome (SIRS) is composed of 4 criteria:Temperature >38 °C or <36 °CHeart rate >90 bpmRespiratory rate >20/min or PaCO2 <32 mm HgWBC >12,000/mm3, <4,000/mm3, or >10% band forms
  • Sepsis = infection with ≥2 SIRS criteria:Release of chemical messengers by the inflammatory responseMacrocirculatory failure through decreased cardiac output or decreased perfusion pressureMicrocirculatory failure through impaired vascular autoregulatory mechanisms and functional shunting of oxygenCytopathic hypoxia and mitochondrial dysfunction
  • Hemodynamic changes result from the inflammatory response:Elevated cardiac output in response to vasodilatationLater myocardial depression:
  • Multiple organ dysfunction syndrome (MODS):Adult respiratory distress syndrome (ARDS)Acute tubular necrosis and kidney failureHepatic injury and failureDisseminated intravascular coagulation
  • Sepsis should be viewed as a continuum of severity from a proinflammatory response to organ dysfunction and tissue hypoperfusion:Severe sepsis: Sepsis with at least 1 of the following organ dysfunctions:AcidosisRenal dysfunctionAcute change in mental statusPulmonary dysfunctionHypotensionThrombocytopenia or coagulopathyLiver dysfunctionSeptic shock: Sepsis-induced hypotension despite fluid resuscitation:Systolic BP <90 mm Hg or reduction of >40 mm Hg from baseline
  • Sepsis is the 10th leading cause of death in US:In-hospital mortality for septic shock is ’ Ό30%

Etiology

  • Gram-negative bacteria most common:Escherichia coliPseudomonas aeruginosaRickettsiaeLegionella spp.
  • Gram-positive bacteria:Enterococcus spp.Staphylococcus aureusStreptococcus pneumoniae
  • Fungi (Candida species)
  • Viruses
  • Children with a minor infection may have many of the findings of SIRS.
  • Major causes of pediatric bacterial sepsis:Neisseria meningitidisStreptococcal pneumoniaHaemophilus influenzae

Diagnosis

Signs and Symptoms

History

  • Question for signs of infection and a systemic inflammatory response:FeverDyspneaAltered mental status:Change in mental statusConfusionDeliriumNausea and vomiting
  • Look for a source of the infection:Cough, shortness of breathAbdominal painDiarrheaDysuria/frequency
  • Past history should highlight risk factors and immunosuppressive states:Underlying terminal illnessRecent chemotherapyMalignancyHistory of a splenectomyHIVDiabetesNursing home resident

Physical Exam

  • An elevated respiratory rate is an early warning sign of sepsis and occurs without underlying pulmonary pathology or acidosis.
  • BP is often normal early in sepsis.
  • Hypotension when septic shock occurs
  • Extremities are often warmed and flushed despite hypotension.
  • Look for a source of the infection:Abdominal examRectal exam to assess for an abscessChest exam for signs of pneumoniaAny rash is important:Localized erythema with lymphangitis (streptococcal or staphylococcal cellulitis)Rash involving palms of hands and soles of feet (rickettsial infection)Petechiae scattered on the torso and extremities (meningococcemia)Ecthyma gangrenosum (pseudomonas septicemia)Round, indurated, painless lesion with surrounding erythema and central necrotic black escharDecubitus ulcersIndwelling catheter:
  • CNS infections:ComaNeck stiffness (meningitis)

Essential Workup

  • Serum lactate should be done early in the course to assess severity and need for goal-directed therapy
  • Blood cultures prior to antibiotics:Broad spectrum of lab tests and imaging studies to locate the source of the infection and assess for MOF.Placement of a central line with an ScvO2 catheter may be used to adjust therapy.

Diagnosis Tests & Interpretation

Lab

  • Serum lactate:>4 mmol/L defines severe sepsisNormal lactate does not rule out septic shock
  • CBC with differential:Leukocytosis is insensitive and nonspecificNeutrophil count <500 cells/mm3 should prompt isolation and empiric IV antibiotics in chemotherapy patients.>5% bands on a peripheral smear is an imperfect indicator of infection.Hematocrit:Patients should be maintained with a hematocrit >30% and hemoglobin >10 g/dL.Platelets:May be elevated in the presence of infection or sepsis-induced volume depletionLow platelet count is a significant predictor of bacteremia and death.
  • Electrolytes, BUN, creatinine, glucose:
  • Ca, Mg, pH
  • C-reactive protein
  • Cortisol level
  • INR/prothrombin time/partial thromboplastin time
  • Liver function tests
  • ABG or VBG:Mixed acid " base abnormalities: Respiratory alkalosis with metabolic acidosisVBG correlates very closely with ABG, except for SaO2
  • Blood cultures:From 2 different sites1 may be drawn through an indwelling central line (i.e., Broviac).
  • Urine analysis and culture

Imaging

  • CXR:Determine whether pneumonia is the infectious source.Fluffy, bilateral infiltrates may indicate that ARDS is already present.Free air under the diaphragm indicates the source of the infection in intraperitoneal and a surgical intervention is mandatory.
  • Soft tissue plain films:Indicated if extremity erythema or severe painAir in the soft tissues associated with necrotizing or gas-forming infection
  • Imaging studies to locate the source of the infection based on the presentation:CT scan of the abdomen and pelvisAbdominal US for gallbladder diseaseTransthoracic or transesophageal echocardiogram

Diagnostic Procedures/Surgery

  • Lumbar puncture:For meningeal signs or altered mental status
  • Central venous access:Central venous pressure (CVP) and ongoing measurement of central venous oximetry.

Differential Diagnosis

  • Pancreatitis
  • Trauma
  • Hemorrhage
  • Cardiogenic shock
  • Toxic shock syndrome
  • Anaphylaxis
  • Adrenal insufficiency
  • Drug or toxin reactions
  • Heavy metal poisoning
  • Hepatic insufficiency
  • Neurogenic shock

Treatment

Pre-Hospital

Aggressive fluid resuscitation for hypotension

Initial Stabilization/Therapy

  • ABCs
  • Supplemental oxygen to maintain PaO2 >60 mm Hg
  • Intubation and mechanical ventilation if shock or hypoxia are present
  • Administer 0.9% NS IV.

Ed Treatment/Procedures

  • Early goal-directed therapy:500 cc boluses of 0.9% saline up to 1 " 2 L empiricallyPlace central line.Continue 500 cc saline boluses until CVP >8 cm H2O.If the mean arterial pressure <65 mm Hg and CVP >8, then initiate pressors:Norepinephrine or dopamine to raise BPNorepinephrine is preferred if tachycardia or dysrhythmias are present.Epinephrine for cases where shock is refractory to other pressorsIf the ScvO2 <70 and HCT <30, transfuse 2 U PRBCs.If ScvO2 >70 and HCT >30 and MAP >60, then add dobutamine.
  • Administer antibiotics early, based on the most likely organisms or site of infection.
  • If source identified, or highly suspected, treat the most likely organisms:Cover for MRSA, VRE, and Pseudomonas if there are risk factorsPulmonary source:2nd- or 3rd-generation cephalosporin and gentamicinIntra-abdominal source:Ampicillin and metronidazole and gentamicinCefoxitin and gentamicinUrinary tract source:Ampicillin or piperacillin and gentamicin or levofloxacin
  • Consider stress-dose hydrocortisone if recent steroid use or possible adrenal insufficiency
  • Antibiotic therapy based on age:<3 mo (2 drugs): Ampicillin and gentamicin or cefotaxime (50 " 180 mg/kg/d div. q4 " 6h) ≥3 mo: Cefotaxime or ceftriaxone (50 " 100 mg/kg/d div. q12 " 24 h)
  • Initiate vasopressors after no response to 60 mL/kg IV fluid.
  • Avoid hyponatremia and hypoglycemia.
  • Dexamethasone for children with bacterial meningitis:0.15 mg/kg q6h for 4 days

Medication

  • Ampicillin: 1 " 2 g (peds: 50 " 200 mg/kg/24 h) IV q4 " 6h
  • Cefoxitin: 1 " 2 g (peds: 100 " 160 mg/kg/24 h) IV q6 " 8h
  • Ceftazidime: 1 " 2 g (peds: 100 " 150 mg/kg/24 h) IV q8 " 12h
  • Dopamine: 1 " 5 Όg/kg/min (renal dose); 5 " 10 Όg/kg/min (pressor dose)
  • Gentamicin: 1 " 1.5 mg/kg (peds: 2 " 2.5 mg/kg q8h) IV q8h
  • Hydrocortisone: 100 mg IV q6 " 8h
  • Metronidazole: Load with 1 g (peds: 15 mg/kg) IV, then 500 mg (peds: 7.5 mg/kg q6h)
  • Nafcillin: 1 " 2 g IV q4h (peds: 50 mg/kg/24 h div. q4 " 6h)
  • Norepinephrine: 2 " 8 Όg/min
  • Piperacillin: 3 " 4 g IV q4 " 6h
  • Vancomycin: 500 mg (peds: 10 mg/kg) IV q6h

First Line

  • Normal immune function without an identifiable source:2nd- or 3rd-generation cephalosporin and gentamicinNafcillin and gentamicinAdd vancomycin if there is a history of methicillin-resistant S. aureus, or the patient resides in a nursing facility, or there is a history of recent hospitalizations.

Second Line

Immunocompromised host without an identifiable source:

  • Piperacillin and gentamicin
  • Ceftazidime and either nafcillin or vancomycin and gentamicin

Follow-Up

Disposition

Admission Criteria

Sepsis almost always requires inpatient care.

Discharge Criteria

Patients with less severe infections (e.g., streptococcal pharyngitis) meeting the criteria for sepsis with stabilized vital signs

Issues for Referral

Sepsis with toxicity, septicemia, or septic shock requires admission, generally to an ICU.

Pearls and Pitfalls

  • Start antibiotics as soon as sepsis is suspected.
  • Failure to recognize multiorgan failure and initiate aggressive fluid resuscitation in the initial presentation of sepsis is a pitfall.

Additional Reading

  • Barochia AV, Cui X, Vitberg D, et al. Bundled care for septic shock: An analysis of clinical trials. Crit Care Med. 2010;38:668 " 678.
  • Martin JB, Wheeler AP. Approach to the patient with sepsis. Clin Chest Med. 2009;30:1 " 16.
  • Rivers E, Nguyen B, Havstad S, et al.; Early Goal-Directed Therapy Collaborative Group. Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med. 2001;345(19):1368 " 1377.
  • Schuetz P, Jones AE, Aird WC, et al. Endothelial cell activation in emergency department patients with sepsis-related and non-sepsis-related hypotension. Shock. 2011;36(2):104 " 108.
  • Shapiro NI, Wolfe RE, Moore RB, et al. Mortality in Emergency Department Sepsis (MEDS) score: A prospectively derived and validated clinical prediction rule. Crit Care Med. 2003;31(3):670 " 675.

Codes

ICD9

  • 038.42 Septicemia due to escherichia coli [E. coli]
  • 038.43 Septicemia due to pseudomonas
  • 995.91 Sepsis
  • 079.99 Unspecified viral infection
  • 038.10 Staphylococcal septicemia, unspecified
  • 038.40 Septicemia due to gram-negative organism, unspecified
  • 038.49 Other septicemia due to gram-negative organisms
  • 038.8 Other specified septicemias
  • 038.9 Unspecified septicemia
  • 083.9 Rickettsiosis, unspecified
  • 995.90 Systemic inflammatory response syndrome, unspecified

ICD10

  • A41.9 Sepsis, unspecified organism
  • A41.51 Sepsis due to Escherichia coli [E. coli]
  • A41.52 Sepsis due to Pseudomonas
  • B34.9 Viral infection, unspecified
  • A40.9 Streptococcal sepsis, unspecified
  • A41.2 Sepsis due to unspecified staphylococcus
  • A41.50 Gram-negative sepsis, unspecified
  • A41.59 Other Gram-negative sepsis
  • A41.81 Sepsis due to Enterococcus
  • B37.7 Candidal sepsis
  • R65.10 SIRS of non-infectious origin w/o acute organ dysfunction

SNOMED

  • 91302008 Systemic infection (disorder)
  • 447899008 Sepsis due to Escherichia coli (disorder)
  • 448813005 Sepsis due to Pseudomonas (disorder)
  • 2528003 viremia (finding)
  • 194394004 Gram positive sepsis (disorder)
  • 238149007 systemic inflammatory response syndrome (disorder)
  • 240446006 Disseminated legionella infection (disorder)
  • 416829003 Disease due to Rickettsia
  • 447841007 Sepsis due to Candida (disorder)
  • 447894003 Sepsis due to Staphylococcus (disorder)