Sepsis: Clinical Spectrum and Management
Jaime Moo-Young, MD
Definitions
Less Severe

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)

More Severe
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 
MAP = (CO x SVR) + CVP

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) 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
CO = cardiac output = stroke volume x heart rate; Hb = hemoglobin; SaO2 = arterial O2 saturation; SvO2 = mixed
venous O2 saturation
*
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 JVPgive 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  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  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 SIRSseptic 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.