SEPSIS
Definition
ACCP/SCCM Consensus (Chest. 1992 Jun;101(6):1644-55.); (Intensive Care Med 2003
Apr;29(4):530)
Clinical syndrome complicating infection with systemic infection and widespread
tissue injury secondary to dysregulation of the normal host inflammatory response
Infection: invasion of sterile host tissues by organisms that leads to an
inflammatory response
Bacteremia: viable bacteria in the blood
SIRS: > 2 of
o HR > 90bpm
o RR > 20 or PaCO2 38.5 or 12,000 or 10% bands
Sepsis: SIRS + culture-proven infection or by visual inspection
Severe sepsis: sepsis + at least one of:
o Mottled skin
o Altered LOC
o Urine output 3s
o Lactate > 2mmol/L
o Platelets 90sBP or >60MAP requires dopamine > 5mcg/kg/min or
norepi 40cc/kg of NS (3-4L) or PCWP b/w 12-20 from a
Swan Ganz
Refractory septic shock: if septic shock needs more than the requirements listed
above
Multiple Organ Dysfunction Syndrome (MODS):
o Primary: insult where organ dysfunction is attributable to the insult itself
(i.e., ARF with rhabdo)
o Secondary: due to the host response (i.e., ARDS in pancreatitis)
o Common predictors include: FaO2 ratio, SCr, plates, GCS, total bili
Epidemiology
2% of hospitalized patients; 75% of ICU patients
Incidence greatest in the winter
Nosocomial infection the most common source
Risk factors:
o Bacteremia in the medical patient
o >65yo
o Immunocompromised
o CAP
Mortality 20-50%
Predictors of Severity
Host response: no fever or low WBC
Co-morbidities: AIDS, liver dz, EtOH, immunocompromised
Age: > 65yo
Site: GI or respiratory
Organism: nosocomial bugs (MRSA, fungus, candida, MSSA, pseudomonas)
Late antibiotic initiation
Pathophysiology
Malignant uncontrolled, unregulated, self-sustaining
Intravascular blood-borne spread from what’s normally cell to cell
Inflammation contains characteristics of the normal inflammatory response
The normal inflammatory process:
o When tissue is injured, there’s usually a balanced activation of
proinflammatory and anti-inflammatory elements
o If this equilibrium is lost, remote tissue injury can occur
o The local inflammatory response is comprised of basic tenets:
Adherence: at the site of injury, the vascular endothelium expresses
adherence molecules to catch leukocytes
PMN’s activate and aggregate at the endothelium of the blood
vessel near the site of injury
Chemotaxis: the move into the tissue via diapedesis
Phagocytosis: engulf the offending organism and release
bacteriocidal elements and recruit other elements of the host system
They release mediators responsible for the cardinal signs of
inflammation (rubor, calor, dolor, tumor)
Hyperemia and local vasodilatation rubor and calor
Increased vascular permeability dolor and tumor
Approach
TREATMENT
Medical emergency
ABC’s:
o Bilateral large bore IV + CENTRAL LINE, O2, monitors
o STAT ABG, CXR, ECG
Blood and urine cultures
Rivers et al (N Engl J Med 2001; 345:1368–1677)
N = 263, single blind RCT evaluating early goal-direct Rx in septic shock
Rationale: sepsis exists along a continuum that sometimes defies early clinical
recognition. Global tissue hypoxia can be a marker for serious illness and can
identify the patient in need of aggressive therapy. Early recognition is important to
treat sepsis during the “golden hours”, where multifaceted treatment provides
maximal benefit
Objective: does recognition and early goal directed therapy (with improved
resuscitative end points) prior to ICU care improve overall mortality, progression to
MODS?
Physical exam, vitals, CVP, U/O unreliable to detect early sepsis
Evidence found that traditional hemodynamic optimization was inadequate
SvO2, lactate, base deficit, pH resuscitation end-points monitored to assess
adequate tissue perfusion/oxygenation
o Recognition of tissue hypoxia is important to ensure early therapy takes
place
Methods:
o 263 patients with:
Septic shock (SIRS + after 30cc/kg bolus of fluid, sBP 4mmol/L)
NO: CHF, pregnancy, CVA, AMI, asthma, GIB, OD, trauma/burn,
chemo pts, immunosuppressed
o Randomized to standard ED care or early goal-directed Rx. Initial
assessment for first 6 hours then transfer to ICU or hospital bed:
All pts: continuous vitals, sepsis labs, monitors, pulse ox, Foley, art
line, central line
Standard care: CVP 8-12; MAP > 65; U/O > 0.5cc/kg/hr
Goal-directed for at least 6 hours: CVP 8-12; MAP > 65; U/O >
0.5cc/kg/hr; ScvO2 > 70%
ScvO2: SaO2 > 93%; HCT > 30; Cardiac Index; VO2
HEIRARCHY OF goal-directed Rx:
o O2 +/- intubation
o Central and arterial lines
o Once lines and O2 placed, each parameters was optimized before moving on
to optimize the next:
o CVP 8-12 500cc NS boluses q30m
o MAP > 65 70% PRBCs until HCT > 30. If still no dobutamine starting at
0.25ug/kg/min increasing 2.5ug/kg/min q30m until goal or max dose of
20ug/kg/min
Used APACHE II score to watch progression
Results:
o No sig base-line difference b/w groups
o Significant results in EGDT v. standard care:
Higher BP (both still met MAP > 65)
Higher ScvO2
Combined goals for CVP, MAP, U/O achieved
Lower base deficit
APACHE II score (16 v. 18)
NNT = 6; ARR 16% 60-day in-hospital mortality (mostly due to
reduction in CV collapse v. MODS)