2. Agenda Discussion is as follows
A brief review of SIRS (systemic inflammatory response
syndrome)
SIRS and it’s role in sepsis
Definitions of the sepsis syndrome
Current sepsis guidelines
MODS
3. Definition
SIRS is a clinical diagnosis, recognized by 2 or more of the
following :
1. Temp >38ºC or <35ºC
2. HR>90bpm
3. RR>20bpm
4. WBC>12000, <4000 or >10% immature (band) forms
Causes
– Acute pancreatitis,
– autoimmune disorders,
– vasculitis,
– thromboembolism,
– burns,
– surgery,
– pulmonary contusion,
– SEPSIS
4. General variables
• Fever (core temp >38.3°C)
• Hypothermia (core temp <36°C)
• Heart rate >90 bpm
• Tachypnea
Inflammatory variables
• Leukocytosis (WBC >12,000)
• Leukopenia (WBC <4000)
• Bandemia (>10% band forms)
• Plasma C-reactive protein >2 s.d. above normal value
• Plasma procalcitonin >2 s.d. above normal value
Altered mental status
• Significant edema or positive fluid balance (>20 mL/kg over 24 h)
• Hyperglycemia in the absence of diabetes
Criteria for systemic inflammatory response syndrome (SIRS)
7. Definitions :
Infection:
A microbial phenomenon characterized by invasion
of normally sterile host tissue by those organisms.
Bacteremia: The presence of viable bacteria in the
blood.
8. Definitions :
Systemic Inflamatory Response
Syndrome (SIRS):
The systemic inflammatory resp
onse to a variety of severe clinic
al insults (For example, infectio
n).
Sepsis:
• Known or suspected infection,
plus
• >2 SIRS Criteria.
9. Severe Sepsis
Sepsis plus at least one of the following:
• Areas of mottled skin
• Capillary refill > 3 seconds
• Urine output < 0.5cc/kg/hr for at least one hour or renal
replacement therapy
• Elevated lactate (>2 to 3)
• Abrupt change in mental status
• Abnormal EEG findings
• Platelet count <100, 000
• DIC
• ARDS
• Cardiac dysfunction
10.
11. INFECTION /
TRAUMA SIRS SEPSIS
SEVERE
SEPSIS
A clinical response arising
from a nonspecific insult,
including 2 of the
following:
– Temperature ≥38oC or
≤36oC
– HR ≥90 beats/min
– Respirations ≥20/min
– WBC count ≥12,000/mm3
or ≤4,000/mm3 or >10%
immature neutrophils
SIRS with a presumed or
confirmed infectious process
16. Septic Shock
Severe sepsis plus at least one of the following:
• MAP<65mmHg despite adequate fluid resuscitation
• Maintaining MAP>60-65mmHg requires vasopressors:
– Dopamine > 5μg/kg/min
– Norepinephrine < 0.25μg/kg/min
– Epinephrine < 0.25mg/min
Refractory Septic Shock
Septic shock that requires higher doses of the ionotropes to ke
ep the MAP>65mmHg:
– Dopamine > 15μg/kg/min
– Norepinephrine > 0.25μg/kg/min
– Epinephrine >0.25mg/min
18. ACUTE PHASE MANAGEMENT OF SEPSIS
Identify Sepsis as early as possible
Broad Spectrum antibiotics and Identify source(s)
of infection
Identify severity: Vitals, mental status, Urine
Output, LACTATE, other labs.
Volume and physiologic resuscitation
19.
20. • Lactate levels are predictive of death and MODS. Clearance of lactate
is associated with improved survival
• Algorithms of care based on lactate clearance appear to work as well
or better than other approaches.
Goals in resuscitation
• Initial fluid resuscitation: CVP 8-12, MAP > 65, UOP 0.5 mL/kg/hr,
ScVO2 70% and Lactate Clearance.
• Give enough volume to maximize stroke volume. Start with 20cc/kg
in most patients.
• Give vasopressors to raise the MAP enough to maintain adequate e
nd-organ perfusion.
• Assessment of Cardiac Function
• UOP and Lactate Clearance are nice global indicators of success.
21. CHRONIC PHASE MANAGEMENT
• Monitor for and prevent recurrence of sepsis
• VAP, CLABSI, UTI. Infection Control Practices.
• Lung Protective Ventilator Strategies
• Nutritional Support
• Early Mobilization
Success with these measures is most likely with a multi-discipli
nary approach
22. Definitions :
Multiple Organ Dysfunction Syndrome (MODS): The
presence of altered organ function in an acutely ill p
atient such that homeostasis cannot be maintained
without intervention
• Primary: secondary to a well defined insult in which organ
dysfunction occurs early and can be directly attributable to
the insult itself (eg: ARF from rhabdomyolysis)
• Secondary: organ failure not in direct response to the insult
itself but as a consequence of a host response to the insult
(eg: ARDS in pancreatitis)
35. Models
Meakins “two-hit” model of
postinjury MOF.
• The first hit (trauma / shock )
primes neutrophils and
macrophages
• The second hit (nosocomial
infection/complication) results
in detrimental inflammatory
response
36. Models
Inflammatory Model
• MODS is caused by an overwhelming imbalance
between systemic inflammatory response and counter
regulation (anti-inflammatory) response.
• May be activated by a number of external and internal
factors, including pro-inflammatory (e.g., infection,
sepsis, shock, and trauma) and immunosuppression
(e.g., Blood transfusion, infection, and steroids) .
• The imbalance in favor of inflammatory response
causes loss of the host's ability to localize the
inflammation to initial inciting factor, leading to
systemic inflammation and tissue damage
38. Models
Bioenergetics Model
• Multiple organ dysfunction is the results of the
dysregulation of mitochondria
• Mitochondrial activity is down-regulated as a
protective reflex to inciting factors
• Failure to recover mitochondrial function
results in self perpetuating cycle of cell
damage furthering shutdown of mitochondria
39. • Pyruvate Dehydrogenase (PDH) activity decreased
• Decreased delivery of Acetyl CoA to TCA cycle
• Mitochondrial dysfunction
43. Gut-liver-lung axis
• The gut can leak inflammatory mediators into the
portal circulation, causing a response in the liver.
• Inflammatory mediators then travel in the hepatic
vein to the inferior vena cava and to the lungs.
• The lungs may become injured and release inflam
matory substances themselves, which travel syste
mically to distant organs (including the gut).
46. Surviving Sepsis Campaign guidelines for
management of severe sepsis and septic shock.
Crit Care Med 2004;32:858-873.)
47. Summary of Surviving Sepsis Campaign guidelines
Initial Evaluation and Infection Issues
• Initial resuscitation
• Target resuscitation to normalize lactate in patients
with elevated lactate levels.
• Diagnosis: Obtain appropriate cultures
• Imaging studies should be performed promptly to c
onfirm a source of infection.
• Antibiotic therapy
• Source control
• Remove intravascular access devices if potentially i
nfected.
• Infection prevention: Selective oral and digestive tra
ct decontamination
48. Hemodynamic Support and Adjunctive Therapy
• Fluid therapy: Fluid resuscitate using crystalloid, usin
g fluid volumes of 1000 mL (crystalloid), target CVP of
8 to12 mm Hg.
• Vasopressors/Inotropic Therapy: Maintain MAP of ≥65
mm Hg, centrally-administered norepinephrine is first-l
ine choice.
• Dopamine should not be used for “renal protection,”
• insert arterial catheters for patients requiring vasopres
sors.
• Phenylephrine is not recommended in treatment of sep
tic shock.
• Dobutamine infusion can be used in setting of myocar
dial dysfunction.
• Steroids: Consider intravenous hydrocortisone (dose ≤
300 mg/d) for adult septic shock when hypotension res
ponds poorly to fluids and vasopressors.
49. Other Supportive Therapy
• Blood product administration: Transfuse when hem
oglobin decreases to <7.0 g/dL.
• Mechanical ventilation: Target an initial tidal volume
of 6 mL/kg body weight and plateau pressure of ≤30
cm H2O in patients with acute lung injury.
• Use positive end-expiratory pressure to avoid lung
collapse. Use a weaning protocol to evaluate the
potential for discontinuing mechanical ventilation.
• Pulmonary artery catheter is not indicated for routin
e monitoring.
50. Other Supportive Therapy
• Sedation: Minimize sedation using specific titration
endpoints.
• Glucose control: Use protocolized approach to bloo
d glucose management targeting upper blood gluco
se target of 180 mg/dL.
• Prophylaxis:
Use proton pump inhibitor for stress ulcers
low-dose unfractionated or fractionated hepar
in deep venous thrombosis prophylaxis.
• Limitation of support: Discuss advance care planni
ng with patients and families and set realistic expec
tations
51. Targeted therapy
• Activated Protein C
– Modulating the systemic inflammatory,
procoagulant, and fibrinolytic host
responses
• Vasopressin Therapy
– Replacing falling plasma levels of
vasopressin seen in shock
52.
53. Activated Protein C Here
• APACHE II score > 25
– No benefit seen in patients w/ APACHE II
score < 25
• More than 1 organ system affected
– Drotrecogin had no benefit in patients
with single organ dysfunction
• Must start Drotrecogin w/in 48 hrs of
1st sign of organ dysfunction
– To achieve benefit seen in PROWESS
drotrecogin should be started w/in 24hrs
• Consider continuing prophylactic
heparin when starting drotrecogin
54. Exclusion Criteria
• Anyone of the following:
– Active bleed
– Recent CVA (w/in 3 months)
– Recent head trauma or
intracranial/spinal surgery (w/in 2
months)
– Intracranial mass lesion or aneurysm <
12 hrs post surgery req. general or
spinal anesthesia
– Epidural catheter
– Trauma patient w/ increased risk of
bleeding
– Patient is moribund
55. Vasopressin Therapy for Septic
Shock
• In early shock, appropriately high levels
of vasopressin are produced to support
organ perfusion.
• As the shock state progresses, plasma
vasopressin levels fall from:
– depletion of pituitary stores of vasopressin
exhaustive release in early septic shock
– central inhibition from elevated norepinephrine
levels (endogenous or exogenous)
– central inhibition from increased nitric oxide
release by vascular endothelium within the
posterior pituitary during sepsis
57. Summary
Identify patients early and identify the seve
rity of sepsis
Quickly administer appropriate antibiotics a
nd source control
Establish institutional goals for physiologic
resuscitation
Multidisciplinary care to ensure compliance
