Sepsis (main)

Background

• Sepsis should be defined as life-threatening organ dysfunction caused by a dysregulated host response to infection
• The infection is most commonly by bacteria, but can also be by fungi, viruses, or parasites
• Risk of death from sepsis being as high as 30%, severe sepsis as high as 50%, and septic shock as high as 80%
• The most common primary sources of infection resulting in sepsis are the lungs, the abdomen, and the urinary tract

Clinical Presentation

SIRS

2 or more of the following:

• Temp >38.3 or <36
• HR >90
• Resp rate >20 or CO2 <32
• WBC >12K, <4K, or >10% bands

Sepsis

• SIRS + documented or suspected infection

Severe sepsis

Sepsis AND 1 or more of the following signs of organ dysfunction:

• Lactate > upper limit of normal
• Urine output <0.5 mL/kg for >2hr, despite adequate fluid resuscitation
• Cr >2 (presumed to be new)
• Bilirubin >2 (presumed to be new)
• Plt <100K (presumed to be new)
• INR >1.5 (presumed to be new)
• Acute Lung Injury
  • PaO2/FIO2 <250 in absence of PNA as infection source
  • PaO2/FIO2 <200 in presence of PNA as infection source

Septic shock

Patients with sepsis and any of the following:

1. Vasopressor requirement to maintain a mean arterial pressure > 65 mm Hg
2. Serum lactate level greater than 2 mmol/L (>18 mg/dL) in the absence of hypovolemia.

Sepsis caries a 40% in hospital mortality

Differential Diagnosis

• Adrenal Insufficiency
• Salicylate Toxicity
• Anticholinergic Toxicity
• Neuroleptic Malignant Syndrome
• Malignant Hyperthermia
• Thyrotoxicosis

Shock

• Cardiogenic
  • Acute valvular Regurgitation/VSD
  • CHF
  • Dysrhythmia
  • ACS
  • Myocardial Contusion
  • Myocarditis
  • Drug toxicity (e.g. beta blocker, CCB, or bupropion OD)
• Obstructive
  • Air embolism
  • Aortic Stenosis
  • Cardiac Tamponade
  • PE
  • Tension pneumothorax
• Distributive
  • Adrenal crisis
  • Anaphylaxis
  • Neurogenic shock
  • Sepsis
  • Toxicologic
• Hypovolemic
  • Severe dehydration
  • Hemorrhagic shock (traumatic and non-traumatic)

Altered mental status and fever

• Infectious
  • Sepsis
  • Meningitis
  • Encephalitis
  • Cerebral malaria
  • Brain abscess
• Other
  • Neuroleptic malignant syndrome
  • Serotonin syndrome
  • Malignant hyperthermia
  • Sympathomimetic toxicity (cocaine, amphetamine, ketamine)
  • Anticholinergic toxicity
  • Heat stroke
  • Delirium tremens
  • Hypothalamic stroke
  • Pheochromocytoma
  • Thyroid storm

Diagnosis

Work-Up

• CBC
• UA/Urine culture
• Blood culture
• CXR
• Chem
• LFT
• Lipase
• VBG
• Lactate
• Procalcitonin
• Coags
• DIC panel (fibrinogen, D-dimer, FDP)
• T&S
• ?CT head/LP
• ?TSH (thyroid storm)
• ?Cosyntropin stim vs. random cortisol (adrenal insufficiency)

Time Specific Management

Time of presentation is defined as the time of triage in the emergency department

3 hour goals

• Measure lactate level
• Obtain blood cultures prior to administration of antibiotics
• Administer broad spectrum antibiotics
• Administer 30ml/kg crystalloid for hypotension or lactate ≥4mmol/L

6 hour goals

• Apply vasopressors (for hypotension that does not respond to initial fluid resuscitation) to maintain a mean arterial pressure (MAP) ≥65mmHg
• If persistent hypotension after initial fluid administration (MAP < 65 mm Hg) or if initial lactate was ≥4 mmol/L, reassess volume status and tissue perfusion:
  • Repeat focused exam OR any two of the following:
    • Measure CVP
    • Measure ScvO
    • Bedside cardiovascular ultrasound
    • Dynamic assessment of fluid responsiveness with passive leg raise or fluid challenge

A central line and measurement of ScvO₂ is not required and does not impact mortality

Circulation

IVF

• Reassess after each bolus
• Average is 5-6L w/in first 6hr
• Careful reassessment of volume status is required in in patients with significantly depressed ejection fraction.

Pressors

• Indicated if MAP<60 despite adequate IVF or if IVF are contraindicated
• Best if given when the vascular space is filled; ok if it's not

Options:

• Norepinephrine (5-20mcg/min) - 1st line
• Epinephrine (1-20 mcg/min) - 2nd line
• Vasopressin (0.03 units/minute fixed dose) can be added to norepinephrine (NE)
• Dopamine should be used hesitantly and only in highly selected patients (eg, patients with low risk of tachyarrhythmias and absolute or relative bradycardia)
  • Do not use Low-dose dopamine for renal protection
• Phenylephrine should not be used for treating septic shock except if:
  • 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

Inotropes

• Dobutamine (2-20mcg/kg/min) may be added if:
  • 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

Steroids

• Controversial and only shown to relieve shock faster in those who have resolution of shock but may increase the risk of infection
  • Consider hydrocortisone 50-100mg in ED (200-300 mg qd in 2-4x/d dosing) if pressor/fluid resistant (SBP < 90 persistently)
• ACTH cosyntropin testing likely unreliable in critically ill patients
• Do not administer steroids for the treatment of sepsis in the absence of shock

Infection Control

• Source Control
• Remove infected lines, surgery if indicated

Antibiotics

• Administer within 3 hours
• See Initial Antibiotics in Sepsis (Main)

Blood Products

RBCs

Only transfuse RBCs when hemoglobin decreases to <7.0 g/dL (goal is 7.0 –9.0 g/dL in adults)

Erythropoietin

Do not use erythropoietin as a specific treatment of anemia associated with severe sepsis

Platelets

• In severe sepsis, administer platelets prophylactically when counts are <10,000/mm3 (10 x 10⁹/L) in the absence of apparent bleeding
• If < 20,000/mm3 (20 x 10⁹/L) and significant risk of bleeding then administer platelets.
• <50,000/mm3 (50 x 10⁹/L) if there is active bleeding, planned surgery or other procedures.

External Links

• MDCalc - SIRS, Sepsis, and Septic Shock Criteria

See Also

• Initial Antibiotics in Sepsis (Main)
• Sepsis (Peds)
• EBQ:ProCESS Trial