septic shock

Introduction

Sepsis leading to hypotension & impaired organ perfusion, unresponsive to fluid therapy.

A subset of sepsis in which underlying circulatory & cellular/ metabolic abnormalities are profound enough to substantially increase mortality.

Etiology

• gram positive bacteria - peptidoglycan/teichoic acid complex
• gram negative bacteria - endotoxins
• fungi - polysaccharide substances in yeast walls
• Rickettsia
• toxins - toxic shock syndrome

Epidemiology

• in New Zealand & Australia death from septic shock in 2012 18%, down from 35% in 2000

Pathology

• hypoxemia
• activation of complement, coagulation, cytokine & arachidonate cascade
• vasodilation, capillary leak
• disseminated intravascular coagulation (DIC)
• myocardial depression
• acute renal failure
• acute liver failure

Clinical manifestations

• hypotension requiring vasopressor for maintain mean arterial pressure > 65 mm Hg

Laboratory

• blood cultures
• complete blood count (CBC)
• serum lactate within 1 hour
  • remeasure with 2-4 hours if > 2 mmol/L
    • > 2 mmol/L despite adequate fluid resuscitation
  • normal serum lactate is one endpoint of resuscitation
• complete metabolic panel
  • electrolytes
  • serum glucose
  • renal function tests
  • liver function tests
• do not perform dexamethasone suppression test

Complications

• adrenocortical insufficiency

Differential diagnosis

• cardiogenic shock
• hypovolemic shock
• adrenal crisis
• obstructive shock

Management

• see distributive shock & sepsis
  • support organ perfusion: maintain mean arterial pressure > 65 mm Hg
  • control infection
• early intervention is more likely to make a difference than invasive monitoring
• one hour sepsis bundle
• initial bolus of IV crystalloid 30 mL/kg
  • no benefit to fluid restriction in patients with septic shock
• assessment of volume responsiveness after initial fluid bolus before initiating vasopressors
• intravenous empiric antimicrobial therapy within 1 hour
  • combination of 2 antibiotics of different class directed at most likely organism(s)
    • generally single active antibiotic agent
  • neutropenic patients & those with P. aeruginosa may have improved outcomes with double-active antibiotic therapy
  • no mortality benefit to antibiotics within 1 hour vs 1-3 hours after emergency department arrival in patients with sepsis or septic shock
• norepinephrine 1st choice as vasopressor for septic shock requiring vasopressors despite fluid resuscitation
  • superior to dopamine, fewer deaths, arrhythmias
  • patients with septic shock more likely to die during a norepinephrine shortage
• no differences between vasopressin & norepinephrine in preserving renal function
• norepinephrine + vasopressin associated with less atrial fibrillation but not lower mortality
• synthetic angiotensin II may have mortality benefit
• maintain mean arterial pressure >= 65 mm Hg who have failed to respond to an initial fluid challenge
  • higher mean arterial pressure target increases risk of atrial fibrillation
  • no mortality benefit in maintaining mean arterial pressure >= 80 mm Hg
  • central venous pressure monitoring & targeting do not improve outcomes
• consider drotrecogin alpha
  • septic shock requiring vasopressors despite fluid resuscitation
  • sepsis-induced ARDS requiring mechanical ventilation with at least two dysfunctional organs
• glucocorticoids
  • low certainty evidence
  • high risk patients may benefit
    • patients with adrenocortical insufficiency
  • no benefit to added vitamin C & thiamine
  • of no benefit
  • not associated with reduced mortality in patients with septic shock who undergo mechanical ventilation
  • low-dose glucocorticoid (hydrocortisone 200 mg QD) not recommended unless systolic blood pressure < 90 mm Hg despite fluids & vasopressors
    • maximum 400 mg hydrocortisone QD
    • 30-day mortality diminished with low-dose glucocorticoids in patients with highest APACHE II scores (51% vs 56%), but may be increased in those with lower scores
  • hydrocortisone + fludrocortisone
    • no benefit for ventilator-free days
    • lower all-cause 90 day mortality (RR=0.88)
• blood transfusion (packed RBC)
  • use standard thresholds (see blood transfusion)
  • transfusion thresholds of 7 g/dL & 9 g/dL result in similar outcomes
• albumin of no survival benefit
  • early albumin may increase need for renal replacement therapy & in-hospital mortality among hospitalized patients with septic shock & chronic renal failure
• esmolol infusion to maintain heart rate between 80-94/min
  • improved survival 51% vs 19% at 28 days
  • did not result in lower blood pressures
  • reduced the need for norepinephrine
• thiamine 500 mg every 8 hours for 72 hours may facilitate plasma lactate clearance & reduce mortality (RR=0.67)
• no mortality benefit to early renal replacement therapy
• strategy targeting normalization of capillary refill time vs strategy targeting serum lactate levels, did not reduce all-cause 28-day mortality
• early enteral nutrition if possible
• glycemic control: insulin to maintain plasma glucose 140-180 mg/dL
• mechanical ventilation:
  • tidal volume 6 mg/kg ideal body weight
  • do not use non-invasive ventilation

Prognosis:

• 40-75% mortality
• poor prognosis associated with:
  • advanced age
  • infection with antimicrobial-resistant organism(s)
  • impaired immunity
  • poor patient functional status
• presention with vague symptoms not specific to infection may result in delayed antibiotic administration & higher risk of mortality
• prevention of septic shock is most important factor in reducing mortality

Notes

• early goal-directed therapy (6 hour resuscitation protocol) of no benefit
• Severe Sepsis/Septic Shock Early Management Bundle (SEP-1)

More general terms

• distributive shock
• sepsis

Additional terms

• Severe Sepsis/Septic Shock Early Management Bundle (SEP-1)