Transcript Surviving Sepsis Campaign Guidelines for Management of

Surviving Sepsis Campaign
Guidelines for Management of
Severe Sepsis/Septic Shock
Resident Education Program
R. Phillip Dellinger, MD
Mitchell M. Levy, MD
Janice L. Zimmerman, MD
Graham Ramsay, MD
For the Surviving Sepsis Campaign
Surviving Sepsis Campaign
(SSC) Guidelines for
Management of Severe Sepsis
and Septic Shock
Dellinger RP, Carlet JM, Masur H, Gerlach H, Calandra T, Cohen J,
Gea-Banacloche J, Keh D, Marshall JC, Parker MM, Ramsay G,
Zimmerman JL, Vincent JL, Levy MM, and the
SSC Management Guidelines Committee
Crit Care Med. 2004;32:858-873
Intensive Care Med. 2004;30:536-555
available online at
www.springerlink.com
www.sccm.org
www.sepsisforum.com
Initial Resuscitation of Sepsisinduced Tissue Hypoperfusion
Sepsis-induced
Tissue Hypoperfusion
Persistent hypotension after initial fluid bolus of 20 ml/kg
crystalloid or colloid equivalent
Lactate > 4.0 mmol/liter
A 62-year-old man comes to the emergency department
with altered mental status, tachycardia, tachypnea, and
hypotension (BP 64/38 mm Hg). He has fever with
leukocytosis, platelet count 75,000, and INR 2.0. A fluid
bolus is being administered. Which adrenergic agents are
most appropriate to maintain blood during fluid bolus and
following fluid bolus if hypotension persists??
A.
B.
C.
D.
Dopamine or epinephrine
Epinephrine or vasopressin
Vasopressin or norepinephrine
Norepinephrine or dopamine
See discussion on next slide
Figure B, page 948, reproduced with permission from
Dellinger RP. Cardiovascular management of septic shock.
Crit Care Med. 2003;31:946-955.
The physiological changes occurring in patients with severe
sepsis and septic shock are myriad and include changes
that are clearly detrimental such as decreased contractility
of the left and right ventricle, increased venous
capacitance, increased pulmonary vascular resistance, and
capillary leak. Increased ventricular compliance and sinus
tachycardia are likely adaptive responses allowing the
ventricle to maintain, and even manifest increased cardiac
input, following volume resuscitation in despite decreased
contractility. The decreased arteriolar resistance may also
be adaptive, although when profound, produces detrimental
and potentially lethal hypotension.
During Septic Shock
See discussion on next slide
Diastole
Systole
10 days post shock
Diastole
Images used with permission from Joseph E. Parrillo, MD
Systole
This slide demonstrates radionuclide angiography in a
patient during septic shock and following recovery. The top
left panel shows end-diastole and demonstrates increased
diastolic size of the ventricles (increased compliance),
which is thought to be an adaptive mechanism. The top
right image shows end-systole in this patient demonstrating
a very low ejection fraction (little change in chamber size
compared to end-diastole). The bottom two frames
following recovery demonstrate a decrease in end-diastole
volume, smaller ventricle at end systole, and therefore
significant improvement in ejection fraction.
Effects of Dopamine, Norepinephrine,
and Epinephrine on the Splanchnic
Circulation in Septic Shock
See discussion on next slide
Figure 2, page 1665, reproduced with permission from De Backer D,
Creteur J, Silva E, Vincent JL. Effects of dopamine, norepinephrine,
and epinephrine on the splanchnic circulation in septic shock: Which
is best? Crit Care Med. 2003;31:1659-1667.
Considerable data (such as that shown on the previous
slide) indicates that epinephrine, although a combined
inotrope/vasopressor, is not the best initial vasopressor of
choice because of concerns with decrease in splanchnic
blood flow. The study above comparing dopamine,
norepinephrine, and epinephrine in moderate shock, and
norepinephrine and epinephrine in severe shock supports
epinephrine-induced decrease in splanchnic blood flow.
Vasopressors
Either norepinephrine or dopamine administered through
a central catheter is the initial vasopressor or choice.
• Failure of fluid resuscitation
• During fluid resuscitation
Following 2 liters of crystalloid infusion, the patient
continues to require vasopressors to maintain systolic
blood pressure of 90 mm Hg. Which one of the following
is the most important intervention?
A.
B.
C.
D.
Infusion of 300 - 500 ml of colloid over 30 minutes
Obtain an estimate of left heart filling pressures
Administration of stress dose steroids
Administration of rh APC
The Importance of Early Goal-Directed
Therapy for Sepsis-induced Hypoperfusion
See discussion on next slide
NNT to prevent 1 event (death) = 6 - 8
60
Mortality (%)
50
Standard therapy
EGDT
40
30
20
10
0
In-hospital
mortality
(all patients)
28-day
mortality
60-day
mortality
Adapted from Table 3, page 1374, with permission from 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;345:1368-1377.
The recommendations for initial resuscitation are centered
around the Rivers trial (above) of early goal-directed
therapy, which showed significant improvement in (a)
hospital mortality, (b) 28-day mortality, and (c) 60-day
mortality.
Initial Resuscitation of Persistent
Hypotension or Lactate > 4 mm/L
Insertion of CVP catheter
Goal:
Central venous pressure: > 8 mm Hg
Fluid Therapy
Fluid resuscitation may consist of natural or artificial
colloids or crystalloids.
Antibiotics
Selection depends on:
•
•
•
•
Presumed site of infection
Gram stain results
Suspected or known organism (includes risk for fungal infection)
Resistance patterns of the hospital
Diagnosis
Appropriate cultures
Minimum two blood cultures
• one percutaneous
• one from each vascular access  48 hours
Antibiotic Therapy
Begin intravenous antibiotics within first hour of
recognition of severe sepsis.
Antibiotic Therapy
One or more drugs active against likely bacterial or
fungal pathogens.
Consider microorganism susceptibility patterns in the
community and hospital.
Antibiotic Therapy
Reassess antimicrobial regimen at 48 - 72 hours
•
•
•
•
Microbiologic and clinical data
Narrow-spectrum antibiotics
Noninfectious cause identified
Prevent resistance, reduce toxicity, reduce costs
Source Control
Evaluate patient for a focused infection amendable to
source control measures including abscess drainage or
tissue debridement.
• Move rapidly
• Consider physiologic upset of measure
• Intravascular access devices
Photograph used with permission from
Janice L. Zimmerman, MD
EKG tracing reproduced with permission from
Janice L. Zimmerman, MD
This picture demonstrates a 38-year-old man with
pharyngitis who presents with high fever, leukocytosis,
hypotension, elevated BUN/creatinine, and early evidence
of coagulopathy who now has redness and swelling of the
anterior neck and chest pain.
An EKG obtained in this patient demonstrates a diffuse ST
segment elevation (or PR depression) diagnostic of
pericarditis, and in this case indicating the presence of
mediastinitis requiring urgent operative drainage of the
mediastinum in order to prevent mortality.
Which of these options is a goal of initial resuscitation that
has been demonstrated to decrease mortality in sepsisinduced tissue hypoperfusion?
A.
B.
C.
D.
Heart rate < 90/min
Mean arterial pressure > 65 mm Hg
Normalization of lactate
Central venous saturation  70%
Guidelines for the Management of
Septic Shock Initial Resuscitation
Goals :
Central venous (superior vena cava) oxyhemoglobin
saturation  70%
Alternative of using mixed venous oxyhemoglobin
saturation from pulmonary artery catheter instead of central
venous O2 saturation from CVP catheter
Reinhart K, et al. Intensive Care Med. 2004;30:1572-1578.
ScvO2 closely paralleled SvO2
but averaged 5 – 7% higher
Reinhart K, et al. Intensive Care Med. 2004;30:1572-1578.
A central line is inserted in the right neck. CVP is 12 mm
Hg. MAP is 70 mm Hg with vasopressor support. Lab
results reveal elevated BUN and creatinine. Arterial gases
reveal pH 7.22, PaCO2 28 torr, and PaO2 65 torr.
Hematocrit is 32% and saturation is 94% with supplement
oxygen. The central venous O2 saturation is 60%.
Which one of the following is most appropriate at this
time?
A.
B.
C.
D.
Packed red blood cells
Intravenous bicarbonate
Dobutamine
Diuresis
Initial Resuscitation
Goals:
Central venous or mixed venous O2 sat < 70% after
CVP of 8 – 12 mm Hg
Packed RBCs to Hct 30%
Dobutamine to max 20 g/kg/min
Bicarbonate Therapy
Bicarbonate therapy not recommended to improve
hemodynamics in patients with lactate induced pH >
7.15
Cooper, et al. Ann Intern Med. 1990;112:492-498.
Mathieu, et al. Crit Care Med. 1991;19:1352-1356.
Changing pH Has Limited Value
See discussion on next slide
Treatment
NaHCO3 (2 mEq/kg)
pH
PAOP
Cardiac output
0.9% NaCl
pH
PAOP
Cardiac output
Before
After
7.22
15
6.7
7.36
17
7.5
7.24
14
6.6
7.23
17
7.3
Cooper DJ, et al. Ann Intern Med. 1990;112:492-498.
Cooper and colleagues compared equimolar amounts of
sodium bicarbonate and normal saline in patients with
vasopressor requiring lactic acidosis (pH range down to
7.15 with mean 7.23) and demonstrated that although pH
was significantly increased with bicarbonate versus
normal saline there was no difference in cardiac output.
There was also no difference between the two groups as
to weaning of vasopressors.
Dobutamine is begun and titrated to 10 g/kg/min with
central venous O2 sat measurement increasing to 72%.
CVP is 12 mm Hg. Norepinephrine is being administered at
5 ug/min with a MAP of 70. Repeat laboratory values include
platelet count of 55,000/mm3 and INR 2.5. Patient is
intubated and mechanically ventilated for ARDS. FIO2 is
1.0, PEEP is 10 cm H2O with PAO2 of 70 mm Hg. Which
one of the following is least indicated at this time?
A.
B.
C.
D.
Increase in end-expiratory pressure
Administration of stress dose steroids
Administration of rh APC
Administration of vasopressin
Circulating Vasopressin Levels in
Septic Shock
See discussion on next slide
Figure 2, page 1755 reproduced with permission from Sharshar
T, Blanchard A, Paillard M, et al. Circulating vasopressin levels
in septic shock. Crit Care Med. 2003;31:1752-1758.
Vasopressin levels are elevated during the initial
presentation of septic shock and then decrease to basal
levels over the next 48 to 96 hours. Since vasopressin
levels are expected to be a normal body response to
hypotension, this occurrence has been labeled as relative
vasopressin deficiency and has led to the use of
vasopressin in patients with septic shock.
Vasopressin and Septic Shock
Vasopressin levels
 Sustained in cardiogenic shock
 Fall over time in septic shock
When administered in septic shock, decreases or
eliminates requirements of traditional pressors
A concern is that as a pure vasopressor expected to
decrease stroke volume and cardiac output
Vasopressors
Vasopressin
Not a replacement for norepinephrine or dopamine as a
first-line agent
Consider in refractory shock despite high-dose
conventional vasopressors
If used, administer at 0.01 - 0.04 units/minute in adults
Steroid Therapy
See discussion on next slide
Figure 2A, page 867, reproduced with permission from Annane D,
Sébille V, Charpentier C, et al. Effect of treatment with low doses of
hydrocortisone and fludrocortisone on mortality in patients with
septic shock. JAMA. 2002;288:862-871.
The largest randomized prospective trial done to study the
effect of stress-dose steroids in septic shock is the “French
multi-center trial,” which targeted “apriori” patients who did
not respond to ATCH stimulation as the group that would
likely benefit from steroid therapy (slide shows results in
that group). This group represented 77% of the population,
and in this group significant improvement in survival by
Kaplan-Meier curve with logistic regression adjustment for
other variables influencing survival was shown.
See discussion on next slide
P = .045
P = .007
Figure 2 and Figure 3, page 648, reproduced with permission from
Bollaert PE, Charpentier C, Levy B, et al. Reversal of late septic shock
with supraphysiologic doses of hydrocortisone. Crit Care Med.
1998;26:645-650.
Figure 2 and Figure 3, page 727, reproduced with permission from
Briegel J, Forst H, Haller M, et al. Stress doses of hydrocortisone
reverse hyperdynamic septic shock: A prospective, randomized,
double-blind, single-center study. Crit Care Med. 1999;27:723-732.
Single center studies also support significant clinical
benefit as to morbidities and/or mortality.
Steroids
Treat patients who still require vasopressors despite fluid
replacement with hydrocortisone 200 - 300 mg/day, for
seven days in three or four divided doses or by
continuous infusion.
Results: 28-day All-cause Mortality
2-sided p-value
Adjusted relative risk reduction
Increase in odds of survival
Primary analysis results
0.005
19.4%
38.1%
35
30.8%
30
24.7%
25
20
15
10
Placebo
(n - 840)
Drotrecogin
alfa (activated)
(n = 850)
5
0
Adapted from Table 4, page 704, with permission from Bernard
GR, Vincent JL, Laterre PF, et al. Efficacy and safety of
recombinant human activated protein C for severe sepsis. N Engl
J Med. 2001;344:699-709.
6.1% absolute
reduction in
mortality
Activated protein C when administered in a blinded,
randomized fashion to over 1,600 patients with severe
sepsis and septic shock produced a 6.1% absolute
reduction in mortality.
Patient Selection for rhAPC
Full support patient
Infection induced organ/system dysfunction as a cause
of high risk of death
Recombinant Human Activated Protein C
(rhAPC)
High risk of death - Any of the following:
•
•
•
•
APACHE II  25
Sepsis-induced multiple organ failure
Septic shock
Sepsis induced ARDS
No absolute contraindications
Weigh relative contraindications
Sepsis Resuscitation Bundle
Serum lactate measured.
Blood cultures obtained prior to antibiotic administration.
From the time of presentation, broad-spectrum antibiotics
administered within three hours for ED admissions and one hour
for non-ED ICU admissions.
In the event of hypotension:
• Minimum of 20 ml/kg of crystalloid (or colloid equivalent) delivered.
• For hypotension not responding to volume resuscitation, vasopressors
employed to maintain mean arterial pressure (MAP) > 65 mm Hg.
In the event of persistent arterial hypotension refractory to
volume resuscitation (septic shock) and/or initial lactate > 4
mmol/L (36 mg/dl):
• Central venous pressure (CVP) of > 8 mm Hg achieved.
• Central venous oxygen saturation (ScvO2) of > 70% achieved.*
*Achieving a mixed venous oxygen saturation (SvO2) of 65% is an acceptable alternative.
Sepsis Management Bundle
Low-dose steroids administered for septic shock in
accordance with a standardized ICU policy.
Drotrecogin alfa (activated) administered in accordance
with a standardized ICU policy.
Glucose control maintained > lower limit of normal, but <
150 mg/dl (8.3 mmol/L).
For mechanically ventilated patients inspiratory plateau
pressures maintained < 30 cm H2O.
www.survivingsepsis.org

A clinician, armed with the sepsis bundles, attacks the three
heads of severe sepsis—hypotension, hypoperfusion, and organ
dysfunction. Crit Care Med. 2004;320(Suppl):S595-S597.
Actual title of painting is “Hercules Kills Cerberus,” by
Renato Pettinato, 2001. Painting hangs in Zuccaro Place
in Agira, Sicily, Italy. Used with permission of artist and
the Rubolotto family.
References
Dellinger RP, Carlet JM, Masur H, et al. Surviving Sepsis
Campaign guidelines for management of severe sepsis and
septic shock. Crit Care Med. 2004;32:858-873.
Dellinger RP. Cardiovascular management of septic shock.
Crit Care Med. 2003;31:946-955.
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;345:1368-1377.
Annane D, Sebille V, Charpentier C, et al. Effect of treatment
with low doses of hydrocortisone and fludrocortisone on
mortality in patients with septic shock. JAMA. 2002;288:862871.
References
Bernard GR, Vincent JL, Laterre PF, et al. Efficacy and safety
of recombinant human activated protein C for severe sepsis.
N Engl J Med. 2001;344:699-709.
Cohen J, Brun-Buisson C, Torres A, et al. Diagnosis of
infection in sepsis: an evidence-based review. Crit Care Med.
2004;32:S466-S494.
Bochud PY, Bonten M, Marchetti O, et al. Antimicrobial
therapy for patients with severe sepsis and septic shock: an
evidence-based review. Crit Care Med. 2004;32:S495-S512.
Marshall JC, Maier RV, Jimenez M, et al. Source control in the
management of severe sepsis and septic shock: an evidencebased review. Crit Care Med. 2004;32:S513-S526.