Sepsis: Clinical Spectrum and Management

Sepsis: Clinical Spectrum and Management

Jaime Moo-Young, MD

Definitions

·  Systemic Inflammatory Response Syndrome (SIRS): ≥ 2 of the following:

o  Temp >38.5° C or <35° C

o  Heart Rate > 90 bpm

o  Resp rate >20 breaths/min or PaCO2 <32 mm Hg

o  WBC > 12,000 or <4,000 cells/mm3, or >10% immature band forms

·  Sepsis: SIRS + culture-proven or visually identified source of infection

(i.e. pneumonia, meningitis, necrotizing fasciitis, etc)

·  Severe Sepsis: Sepsis + ≥ 1 signs of end-organ damage:

o  Mottled skin

o  Decreased urine output (<0.5 mL/kg/hr)*

o  Serum lactate >2 mmol/L*

o  Altered mental status*

o  Disseminated Intravascular Coagulation (DIC)

·  Septic Shock: Severe Sepsis + Hypotension defined as ≥1 of the following:

o  Mean arterial pressure <60 mm Hg despite adequate fluids,

o  Need pressors (dopamine, norepinephrine, epinephrine) to maintain MAP >60

Physiologic Parameters to Monitor

V = IR à

·  Central Venous Pressure (CVP)

o  What it is: Estimation of R atrial ≈ thoracic vena cava pressure

o  What it indicates: Volume status, i.e. preload

o  Goal: 8-12 mm Hg (4-6 mm Hg if ARDS after early resusciation)

·  Mean Arterial Pressure (MAP)

o  What it is: The perfusing blood pressure that pumps blood through the body to end organs.

MAP = 2/3(diastolic BP) + 1/3 (systolic BP)

o  What it indicates: Ability to perfuse end organs

o  Goal ≥ 65

·  Urine Output

o  What it indicates: how well kidneys are being perfused

o  Goal: ≥ 0.5 cc/kg/hr (= 35 cc/hr in a 70 kg person)

·  Mixed Venous Oxygen Saturation (SVO2)

o  What it is: percentage of oxygen bound to blood returning to the R side of the heart from rest of the body (= “leftover” oxygen after tissues have extracted what they need).

o  What it indicates: How adequate O2 delivery and cardiac output are to meet end organs’ needs

o  How to calculate it: O2 consumption = (CO x Hb) x (SaO2 –SvO2)à Solving for SvO2 gives: SvO2 = SaO2 – (O2 consumption/ (CO x Hb)[*]

o  Goal: >70%

Managing Sepsis: Early Goal-Directed Therapy (Rivers et al, NEJM 2001;345:1368)

1.  ABC’s

·  Airway and Breathing: Stabilize O2 saturation with supplemental O2 or intubation

·  Circulation: Assess perfusion by taking frequent BP’s, ideally with arterial line

2.  Fluid resusciation of circulation

·  Isotonic crystalloid (NS or Lactated Ringer’s) as good as albumin

·  Goals: get lactate <2, CVP >8, MAP ≥65, urine output ≥ 0.5 cc/kg/hr

·  Most important step of sepsis mangament! May require >5L within first 6 hrs

·  Do not delay fluids to determine infection source or place a line

3.  Determine and Control Infection source

·  Blood cultures x 2 sets, ideally before starting ABX

·  Start empiric antibiotics within 1 hour of recognized sepsis

o  Use broad-spectrum (gram +, gram -) if source not immediately obvious

o  Consider fungemia in immunosuppressed pts

o  Avoid using 2 antibiotics from the same class (i.e. B-lactams)

o  Take pt’s allergies, antibiotic history, and resistance patterns into account

·  Get urine cultures and CXR unless alternative source is obvious

·  If evidence of sequestered infection (i.e abscess), drain it.

4.  Determine and manage Volume status

·  Insert central venous catheter where available, and transduce CVP.

·  Surrogates for CVP: 1) Bedside ultrasound to estimate internal jugular filling pressure; 2) physical exam to estimate JVPàgive fluids until JVP ≥ 8

·  If CVP <8 and MAP still ≤ 65, give more fluids until CVP at goal.

·  If CVP >12 and MAP <65, start vasopressors

·  If cannot measure JVP or CVP, minimal adequate fluid resusciation = 40-60 mL/kg of isotonic fluid

5.  Start vasopressors if indicated.

·  First line = norepinephrine. Preferred to dopamine due to ò arrhythmogenic effects

·  Second line: May add vasopressin to norepi, but no data to show improved outcomes

6.  Determine and manage tissue perfusion.

·  Measure ScVO2 via central line

·  Surrogates for ScVO2: 1) SvO2 from VBG; 2) Hemoglobin measurement

·  Goal >70%

·  If <70%, consider blood transfusion to goal Hb of 7

·  If cannot measure ScVO2 exactly, try to optimize SaO2, Hb, and CO

·  Be cautious with blood transfusions, as can increase risk of ARDS

* Time frame = within 6 hours for all the above steps. Shown to ò mortality by >40% !!**

Adjuncts to Early Goal-directed Therapy

·  Steroids:

o  Data to support corticosteroid administration in fluid and pressor-refractory shock is conflicting.

o  May transiently improve blood pressures but lead to more superinfection.

·  Glycemic Control:

o  Data to support aggressive glycemic control to 80-110 mg/dL is controversial.

o  Risk of overly aggressive glycemic control can lead to hypoglycemic episodes and/or mortality risk

o  May consider keeping glucose <150 mg/dL

Key Points

·  The progression of SIRS to septic shock occurs along a continuum.

·  Learn how to recognize the warning signs of SIRSàseptic shock early so that you can intervene ASAP.

·  When in doubt, give fluids early and generously (within 6 hours is key).

·  Attaining hemodynamic goals within 6 hours can reduce mortality by >40%.

·  Do not delay empiric antibiotics to place lines, draw cultures, or obtain other diagnostic data.

·  In the absence of high-technology monitoring, physical exam findings are your friend.

References:

1.  Rivers E, Nguyen B, Havstad S, et al. Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med 2001; 345:1368.

2.  www.uptodate.com

3.  Sabatine et al. Pocket Medicine, Fourth Edition. Wolters Kluwer, Lippincott Williams & Wilkins, 2010.

4.  McGee, Steven. Evidence Based Physical Diagnosis. Philadelphia: Saunders, 2007.

[*] CO = cardiac output = stroke volume x heart rate; Hb = hemoglobin; SaO2 = arterial O2 saturation; SvO2 = mixed venous O2 saturation