Bahan Anes

8/18/2019 Bahan Anes

1/30

INTRODUCTION — Sepsis is a clinical syndrome characterized by systemic inflammation due to

infection. There is a continuum of severity ranging from sepsis to severe sepsis and septic shock. Over

1,66,!!! cases of sepsis occur in the "nited States each year, #ith a mortality rate up to ! percent $ 1%.

&ven #ith optimal treatment, mortality due to severe sepsis or septic shock is appro'imately (! percent

and can e'ceed ! percent in the sickest patients $)*%.

+n this topic revie#, the management of severe sepsis and septic shock is discussed. efinitions,

diagnosis, pathophysiology, and investigational therapies for sepsis, as #ell as management of sepsis in

the asplenic patient are revie#ed separately. -See Sepsis and the systemic inflammatory response

syndrome/ efinitions, epidemiology, and prognosis and 0athophysiology of sepsis and +nvestigational

and ineffective therapies for sepsis and linical features and management of sepsis in the asplenic

patient.2

THERAPEUTIC PRIORITIES — The early administration of fluids and antibiotics is the cornerstone of

management for patients #ith severe sepsis and septic shock.

Therapeutic priorities for patients #ith severe sepsis or septic shock include/

3&arly initiation of supportive care to correct physiologic abnormalities, such as hypo'emia and

hypotension $6*4%.

3istinguishing sepsis from systemic inflammatory response syndrome -S+5S2 - table 12 because, if

an infection e'ists, it must be identified and treated as soon as possible -table )2. This may reuire

appropriate antibiotics as #ell as a surgical procedure -eg, drainage2.

EARLY MANAGEMENT — The first priority in any patient #ith severe sepsis or septic shock is

stabilization of their air#ay and breathing. 7e't, perfusion to the peripheral tissues should be restored and

antibiotics administered $4,1!%.

Stabilize respiration — Supplemental o'ygen should be supplied to all patients #ith sepsis and

o'ygenation should be monitored continuously #ith pulse o'imetry. +ntubation and mechanical ventilationmay be reuired to support the increased #ork of breathing that typically accompanies sepsis, or for

air#ay protection since encephalopathy and a depressed level of consciousness freuently complicate

sepsis $11,1)%.

The choice and use of sedative and induction agents -eg, etomidate, ketamine2 used to intubate patients

#ith severe sepsis or septic shock are discussed separately. Other aspects of intubation and mechanical

ventilation are similarly described else#here. -See Sedation or induction agents for rapid seuence

intubation in adults and 8dvanced emergency air#ay management in adults and 5apid seuence

intubation in adults and The decision to intubate and The difficult air#ay in adults.2

hest radiographs and arterial blood gas analysis should be obtained follo#ing initial stabilization. These

studies are used in combination #ith other clinical parameters to diagnose acute respiratory distress

syndrome -85S2, #hich freuently complicates sepsis. -See 8cute respiratory distress syndrome/

linical features and diagnosis in adults and 9echanical ventilation of adults in acute respiratory

distress syndrome.2

Assess per!sion — Once the patient:s respiratory status has been stabilized, the adeuacy of perfusion

should be assessed. ;ypotension is the most common sign but critical hypoperfusion can also occur in

http://www.uptodate.com/contents/evaluation-and-management-of-severe-sepsis-and-septic-shock-in-adults/abstract/1http://www.uptodate.com/contents/evaluation-and-management-of-severe-sepsis-and-septic-shock-in-adults/abstract/1http://www.uptodate.com/contents/evaluation-and-management-of-severe-sepsis-and-septic-shock-in-adults/abstract/2-5http://www.uptodate.com/contents/sepsis-and-the-systemic-inflammatory-response-syndrome-definitions-epidemiology-and-prognosis?source=see_linkhttp://www.uptodate.com/contents/sepsis-and-the-systemic-inflammatory-response-syndrome-definitions-epidemiology-and-prognosis?source=see_linkhttp://www.uptodate.com/contents/sepsis-and-the-systemic-inflammatory-response-syndrome-definitions-epidemiology-and-prognosis?source=see_linkhttp://www.uptodate.com/contents/pathophysiology-of-sepsis?source=see_linkhttp://www.uptodate.com/contents/pathophysiology-of-sepsis?source=see_linkhttp://www.uptodate.com/contents/investigational-and-ineffective-therapies-for-sepsis?source=see_linkhttp://www.uptodate.com/contents/investigational-and-ineffective-therapies-for-sepsis?source=see_linkhttp://www.uptodate.com/contents/investigational-and-ineffective-therapies-for-sepsis?source=see_linkhttp://www.uptodate.com/contents/investigational-and-ineffective-therapies-for-sepsis?source=see_linkhttp://www.uptodate.com/contents/clinical-features-and-management-of-sepsis-in-the-asplenic-patient?source=see_linkhttp://www.uptodate.com/contents/clinical-features-and-management-of-sepsis-in-the-asplenic-patient?source=see_linkhttp://www.uptodate.com/contents/evaluation-and-management-of-severe-sepsis-and-septic-shock-in-adults/abstract/6-9http://www.uptodate.com/contents/evaluation-and-management-of-severe-sepsis-and-septic-shock-in-adults/abstract/6-9http://www.uptodate.com/content-not-availablehttp://www.uptodate.com/content-not-availablehttp://www.uptodate.com/contents/evaluation-and-management-of-severe-sepsis-and-septic-shock-in-adults/abstract/9,10http://www.uptodate.com/contents/evaluation-and-management-of-severe-sepsis-and-septic-shock-in-adults/abstract/9,10http://www.uptodate.com/contents/evaluation-and-management-of-severe-sepsis-and-septic-shock-in-adults/abstract/11,12http://www.uptodate.com/contents/etomidate-drug-information?source=see_linkhttp://www.uptodate.com/contents/ketamine-drug-information?source=see_linkhttp://www.uptodate.com/contents/ketamine-drug-information?source=see_linkhttp://www.uptodate.com/contents/sedation-or-induction-agents-for-rapid-sequence-intubation-in-adults?source=see_linkhttp://www.uptodate.com/contents/sedation-or-induction-agents-for-rapid-sequence-intubation-in-adults?source=see_linkhttp://www.uptodate.com/contents/sedation-or-induction-agents-for-rapid-sequence-intubation-in-adults?source=see_linkhttp://www.uptodate.com/contents/advanced-emergency-airway-management-in-adults?source=see_linkhttp://www.uptodate.com/contents/rapid-sequence-intubation-in-adults?source=see_linkhttp://www.uptodate.com/contents/rapid-sequence-intubation-in-adults?source=see_linkhttp://www.uptodate.com/contents/the-decision-to-intubate?source=see_linkhttp://www.uptodate.com/contents/the-decision-to-intubate?source=see_linkhttp://www.uptodate.com/contents/the-difficult-airway-in-adults?source=see_linkhttp://www.uptodate.com/contents/the-difficult-airway-in-adults?source=see_linkhttp://www.uptodate.com/contents/acute-respiratory-distress-syndrome-clinical-features-and-diagnosis-in-adults?source=see_linkhttp://www.uptodate.com/contents/acute-respiratory-distress-syndrome-clinical-features-and-diagnosis-in-adults?source=see_linkhttp://www.uptodate.com/contents/mechanical-ventilation-of-adults-in-acute-respiratory-distress-syndrome?source=see_linkhttp://www.uptodate.com/contents/mechanical-ventilation-of-adults-in-acute-respiratory-distress-syndrome?source=see_linkhttp://www.uptodate.com/contents/evaluation-and-management-of-severe-sepsis-and-septic-shock-in-adults/abstract/2-5http://www.uptodate.com/contents/sepsis-and-the-systemic-inflammatory-response-syndrome-definitions-epidemiology-and-prognosis?source=see_linkhttp://www.uptodate.com/contents/sepsis-and-the-systemic-inflammatory-response-syndrome-definitions-epidemiology-and-prognosis?source=see_linkhttp://www.uptodate.com/contents/pathophysiology-of-sepsis?source=see_linkhttp://www.uptodate.com/contents/investigational-and-ineffective-therapies-for-sepsis?source=see_linkhttp://www.uptodate.com/contents/investigational-and-ineffective-therapies-for-sepsis?source=see_linkhttp://www.uptodate.com/contents/clinical-features-and-management-of-sepsis-in-the-asplenic-patient?source=see_linkhttp://www.uptodate.com/contents/clinical-features-and-management-of-sepsis-in-the-asplenic-patient?source=see_linkhttp://www.uptodate.com/contents/evaluation-and-management-of-severe-sepsis-and-septic-shock-in-adults/abstract/6-9http://www.uptodate.com/content-not-availablehttp://www.uptodate.com/content-not-availablehttp://www.uptodate.com/contents/evaluation-and-management-of-severe-sepsis-and-septic-shock-in-adults/abstract/9,10http://www.uptodate.com/contents/evaluation-and-management-of-severe-sepsis-and-septic-shock-in-adults/abstract/11,12http://www.uptodate.com/contents/etomidate-drug-information?source=see_linkhttp://www.uptodate.com/contents/ketamine-drug-information?source=see_linkhttp://www.uptodate.com/contents/sedation-or-induction-agents-for-rapid-sequence-intubation-in-adults?source=see_linkhttp://www.uptodate.com/contents/sedation-or-induction-agents-for-rapid-sequence-intubation-in-adults?source=see_linkhttp://www.uptodate.com/contents/advanced-emergency-airway-management-in-adults?source=see_linkhttp://www.uptodate.com/contents/rapid-sequence-intubation-in-adults?source=see_linkhttp://www.uptodate.com/contents/rapid-sequence-intubation-in-adults?source=see_linkhttp://www.uptodate.com/contents/the-decision-to-intubate?source=see_linkhttp://www.uptodate.com/contents/the-difficult-airway-in-adults?source=see_linkhttp://www.uptodate.com/contents/acute-respiratory-distress-syndrome-clinical-features-and-diagnosis-in-adults?source=see_linkhttp://www.uptodate.com/contents/acute-respiratory-distress-syndrome-clinical-features-and-diagnosis-in-adults?source=see_linkhttp://www.uptodate.com/contents/mechanical-ventilation-of-adults-in-acute-respiratory-distress-syndrome?source=see_linkhttp://www.uptodate.com/contents/mechanical-ventilation-of-adults-in-acute-respiratory-distress-syndrome?source=see_linkhttp://www.uptodate.com/contents/evaluation-and-management-of-severe-sepsis-and-septic-shock-in-adults/abstract/1


2/30

the absence of hypotension, especially during early sepsis. linical signs of impaired perfusion include

the follo#ing/

3Hypotension < ;ypotension is the most common indicator that perfusion is inadeuate -eg,

systolic blood pressure $S=0% >4! mm;g, mean arterial pressure >?! mm;g, decrease in S=0 @(!

mm;g2. Therefore, it is important that the blood pressure be assessed early and often. =ecause a

sphygmomanometer may be unreliable in hypotensive patients, an arterial catheter may be inserted

if blood pressure is labile or restoration of arterial perfusion pressures is e'pected to be a protracted

process $A%. 8ttempts to insert an arterial line should not delay the prompt management of shock.

-See8rterial catheterization techniues for invasive monitoring.2

3Si"ns o poor en#$or"an per!sion < Barm, flushed skin may be present in the early phases of

sepsis. 8s sepsis progresses to shock, the skin may become cool due to redirection of blood flo# to

core organs. 8dditional signs of hypoperfusion include tachycardia @4! per min, obtundation or

restlessness, and oliguria or anuria.

These findings may be modified by pree'isting disease or medications. 8s e'amples, older patients,

diabetic patients, and patients #ho take beta*blockers may not e'hibit an appropriate tachycardia asblood pressure falls. +n contrast, younger patients freuently develop a severe and prolonged

tachycardia and fail to become hypotensive until acute decompensation later occurs, often suddenly.

0atients #ith chronic hypertension may develop critical hypoperfusion at a higher blood pressure

than healthy patients -ie, relative hypotension2.

3Ele%ate# la&tate < 8n elevated serum lactate -eg, @) mmolCD2 can be a manifestation of organ

hypoperfusion in the presence or absence of hypotension and is an important component of the

initial evaluation $4,1E,1(%. 8 serum lactate level F( mmolCD is consistent #ith, but not diagnostic of,

severe sepsis. 8dditional laboratory studies that help characterize the severity of sepsis include a

lo# platelet count, and elevated international normalized ratio, creatinine, and bilirubin. Galues for

laboratory parameters that suggest severe sepsis are described separately. -See Sepsis and the

systemic inflammatory response syndrome/ efinitions, epidemiology, and prognosis, section on:Severe sepsis:.2

3Ot'er < Tests that combine output from many organs -eg, arterial lactate2 may obscure the

presence of significant ischemia in an individual organ $1%. Hastric tonometry indirectly measures

perfusion to the gut by estimating the gastric mucosal 0O). +t can be used to detect gut hypo'ia by

calculating the gastric to arterial 0O) gap $1*1?%. =ut, gastric tonometry is not #idely available and

it is uncertain #hether it can successfully guide therapy. 8dditional studies and clinical e'perience

are needed.

Establis' %eno!s a&&ess — Genous access should be established as soon as possible in patients #ith

suspected sepsis. Bhile peripheral venous access may be sufficient in some patients, particularly for

initial resuscitation, the maIority #ill reuire central venous access at some point during their course. 8central venous catheter -G2 can be used to infuse intravenous fluids, medications -particularly

vasopressors2, and blood products, as #ell as to dra# blood for freuent laboratory studies. +n addition,

this access can be used for hemodynamic monitoring by measuring the central venous pressure -G02

and the central venous o'yhemoglobin saturation -ScvO)2. Bhile in the past, a maIor purpose of a G

#as the measurement of ScGO) and G0, evidence from randomized trials on the value these targets to

follo# therapeutic effect is conflicting $1A*)!%. -See :Hoals of initial resuscitation: belo#

and omplications of central venous catheters and their prevention.2

http://www.uptodate.com/contents/evaluation-and-management-of-severe-sepsis-and-septic-shock-in-adults/abstract/8http://www.uptodate.com/contents/evaluation-and-management-of-severe-sepsis-and-septic-shock-in-adults/abstract/8http://www.uptodate.com/contents/arterial-catheterization-techniques-for-invasive-monitoring?source=see_linkhttp://www.uptodate.com/contents/evaluation-and-management-of-severe-sepsis-and-septic-shock-in-adults/abstract/9,13,14http://www.uptodate.com/contents/evaluation-and-management-of-severe-sepsis-and-septic-shock-in-adults/abstract/9,13,14http://www.uptodate.com/contents/sepsis-and-the-systemic-inflammatory-response-syndrome-definitions-epidemiology-and-prognosis?source=see_link&sectionName=Severe+sepsis&anchor=H7#H7http://www.uptodate.com/contents/sepsis-and-the-systemic-inflammatory-response-syndrome-definitions-epidemiology-and-prognosis?source=see_link&sectionName=Severe+sepsis&anchor=H7#H7http://www.uptodate.com/contents/sepsis-and-the-systemic-inflammatory-response-syndrome-definitions-epidemiology-and-prognosis?source=see_link&sectionName=Severe+sepsis&anchor=H7#H7http://www.uptodate.com/contents/evaluation-and-management-of-severe-sepsis-and-septic-shock-in-adults/abstract/15http://www.uptodate.com/contents/evaluation-and-management-of-severe-sepsis-and-septic-shock-in-adults/abstract/15-17http://www.uptodate.com/contents/evaluation-and-management-of-severe-sepsis-and-septic-shock-in-adults/abstract/15-17http://www.uptodate.com/contents/evaluation-and-management-of-severe-sepsis-and-septic-shock-in-adults/abstract/18-20http://www.uptodate.com/contents/evaluation-and-management-of-severe-sepsis-and-septic-shock-in-adults/abstract/18-20http://www.uptodate.com/contents/evaluation-and-management-of-severe-sepsis-and-septic-shock-in-adults#H465648352http://www.uptodate.com/contents/complications-of-central-venous-catheters-and-their-prevention?source=see_linkhttp://www.uptodate.com/contents/complications-of-central-venous-catheters-and-their-prevention?source=see_linkhttp://www.uptodate.com/contents/complications-of-central-venous-catheters-and-their-prevention?source=see_linkhttp://www.uptodate.com/contents/evaluation-and-management-of-severe-sepsis-and-septic-shock-in-adults/abstract/8http://www.uptodate.com/contents/arterial-catheterization-techniques-for-invasive-monitoring?source=see_linkhttp://www.uptodate.com/contents/evaluation-and-management-of-severe-sepsis-and-septic-shock-in-adults/abstract/9,13,14http://www.uptodate.com/contents/sepsis-and-the-systemic-inflammatory-response-syndrome-definitions-epidemiology-and-prognosis?source=see_link&sectionName=Severe+sepsis&anchor=H7#H7http://www.uptodate.com/contents/sepsis-and-the-systemic-inflammatory-response-syndrome-definitions-epidemiology-and-prognosis?source=see_link&sectionName=Severe+sepsis&anchor=H7#H7http://www.uptodate.com/contents/sepsis-and-the-systemic-inflammatory-response-syndrome-definitions-epidemiology-and-prognosis?source=see_link&sectionName=Severe+sepsis&anchor=H7#H7http://www.uptodate.com/contents/evaluation-and-management-of-severe-sepsis-and-septic-shock-in-adults/abstract/15http://www.uptodate.com/contents/evaluation-and-management-of-severe-sepsis-and-septic-shock-in-adults/abstract/15-17http://www.uptodate.com/contents/evaluation-and-management-of-severe-sepsis-and-septic-shock-in-adults/abstract/18-20http://www.uptodate.com/contents/evaluation-and-management-of-severe-sepsis-and-septic-shock-in-adults#H465648352http://www.uptodate.com/contents/complications-of-central-venous-catheters-and-their-prevention?source=see_link


3/30

Be believe that pulmonary artery catheters -08s2 should not be used in the routine management of

patients #ith severe sepsis or septic shock. 08s can measure the pulmonary artery occlusion pressure

-08O02 and mi'ed venous o'yhemoglobin saturation -SvO)2. +n theory, this may be helpful to guide

circulatory resuscitation. ;o#ever, the 08O0 has proven to be a poor predictor of fluid responsiveness in

sepsis and the SvO) is similar to the ScvO), #hich can be obtained from a G $)1,))%. 08s increase

complications and have not been sho#n to improve outcome $)E*)%. -See 0ulmonary arterycatheterization/ +ndications, contraindications, and complications in adults.2

Inter%entions to restore per!sion — The rapid restoration of perfusion is predominantly achieved by

the administration of intravenous fluids, usually crystalloids. 9odalities such as vasopressor therapy,

inotropic therapy, and blood transfusion are added, depending on the response to fluid resuscitation,

evidence for myocardial dysfunction, and presence of anemia. -See Treatment of severe hypovolemia or

hypovolemic shock in adults.2

Intra%eno!s l!i#s — +n patients #ith sepsis, intravascular hypovolemia is typical and may be severe,

reuiring rapid fluid resuscitation.

(ol!)e — The optimal volume of resuscitative fluid is unkno#n. Several studies of early goal directedtherapy reported intravenous fluid infusions targeted to physiologic endpoints and resulted in volumes

ranging from E to liters $1A*)!%. The volume of fluid that #as administered #ithin the initial si' hours of

presentation #as targeted to set physiologic endpoints -eg, mean arterial pressure2. Bhile an early study

of early goal*directed therapy -&HT2 reported mean infusion volume in the first si' hours of E to liters

$1A%, later trials reporting mean infusion volumes of ) to E liters $ 14,)!%. Thus, rapid, large volume

infusions of intravenous fluids are indicated as initial therapy for severe sepsis or septic shock, unless

there is coe'isting clinical or radiographic evidence of heart failure. Suggested targets for fluid

resuscitation are discussed separately. -See :Hoals of initial resuscitation: belo#.2

Jluid therapy should be administered in #ell*defined -eg, !! mD2, rapidly infused boluses $ 4%. Golume

status, tissue perfusion, blood pressure, and the presence or absence of pulmonary edema must be

assessed before and after each bolus. +ntravenous fluid challenges can be repeated until blood pressure

and tissue perfusion are acceptable, pulmonary edema ensues, or fluid fails to augment perfusion.

areful monitoring is essential because patients #ith sepsis may develop noncardiogenic pulmonary

edema -ie, 85S2. Once patients #ith 85S have been fluid resuscitated a liberal approach to

intravenous fluid administration has been sho#n to prolong the duration of mechanical ventilation,

compared to a more restrictive approach that also typically reuires large doses of furosemide $)6%. +n

addition, small retrospective studies have reported that fluid overload is common in patients #ith sepsis

and is associated #ith the increased performance of medical interventions -eg, diuresis, thoracentesis2K

the effect of fluid overload and such interventions on mortality is unclear $)?,)A%. Thus, #hile the early,

aggressive fluid therapy is appropriate in severe sepsis and septic shock, fluids may be unhelpful or

harmful #hen the circulation is no longer fluid*responsive. -See 8cute respiratory distress syndrome/Supportive care and o'ygenation in adults, section on :Jluid management:.2

C'oi&e o l!i# — &vidence from randomized trials and meta*analyses have found no convincing

difference bet#een using albumin solutions and crystalloid solutions -eg, normal saline, 5ingerLs lactate2

in the treatment of severe sepsis or septic shock, but they have identified potential harm from

usingpentastarch or hydro'yethyl starch rather than a crystalloid solution $)4*E%/

http://www.uptodate.com/contents/evaluation-and-management-of-severe-sepsis-and-septic-shock-in-adults/abstract/21,22http://www.uptodate.com/contents/evaluation-and-management-of-severe-sepsis-and-septic-shock-in-adults/abstract/23-25http://www.uptodate.com/contents/pulmonary-artery-catheterization-indications-contraindications-and-complications-in-adults?source=see_linkhttp://www.uptodate.com/contents/pulmonary-artery-catheterization-indications-contraindications-and-complications-in-adults?source=see_linkhttp://www.uptodate.com/contents/treatment-of-severe-hypovolemia-or-hypovolemic-shock-in-adults?source=see_linkhttp://www.uptodate.com/contents/treatment-of-severe-hypovolemia-or-hypovolemic-shock-in-adults?source=see_linkhttp://www.uptodate.com/contents/treatment-of-severe-hypovolemia-or-hypovolemic-shock-in-adults?source=see_linkhttp://www.uptodate.com/contents/evaluation-and-management-of-severe-sepsis-and-septic-shock-in-adults/abstract/18-20http://www.uptodate.com/contents/evaluation-and-management-of-severe-sepsis-and-septic-shock-in-adults/abstract/18http://www.uptodate.com/contents/evaluation-and-management-of-severe-sepsis-and-septic-shock-in-adults/abstract/19,20http://www.uptodate.com/contents/evaluation-and-management-of-severe-sepsis-and-septic-shock-in-adults#H465648352http://www.uptodate.com/contents/evaluation-and-management-of-severe-sepsis-and-septic-shock-in-adults/abstract/9http://www.uptodate.com/contents/furosemide-drug-information?source=see_linkhttp://www.uptodate.com/contents/evaluation-and-management-of-severe-sepsis-and-septic-shock-in-adults/abstract/26http://www.uptodate.com/contents/evaluation-and-management-of-severe-sepsis-and-septic-shock-in-adults/abstract/27,28http://www.uptodate.com/contents/acute-respiratory-distress-syndrome-supportive-care-and-oxygenation-in-adults?source=see_link&sectionName=Fluid+management&anchor=H15#H15http://www.uptodate.com/contents/acute-respiratory-distress-syndrome-supportive-care-and-oxygenation-in-adults?source=see_link&sectionName=Fluid+management&anchor=H15#H15http://www.uptodate.com/contents/acute-respiratory-distress-syndrome-supportive-care-and-oxygenation-in-adults?source=see_link&sectionName=Fluid+management&anchor=H15#H15http://www.uptodate.com/contents/acute-respiratory-distress-syndrome-supportive-care-and-oxygenation-in-adults?source=see_link&sectionName=Fluid+management&anchor=H15#H15http://www.uptodate.com/contents/pentastarch-drug-information?source=see_linkhttp://www.uptodate.com/contents/evaluation-and-management-of-severe-sepsis-and-septic-shock-in-adults/abstract/29-35http://www.uptodate.com/contents/evaluation-and-management-of-severe-sepsis-and-septic-shock-in-adults/abstract/21,22http://www.uptodate.com/contents/evaluation-and-management-of-severe-sepsis-and-septic-shock-in-adults/abstract/23-25http://www.uptodate.com/contents/pulmonary-artery-catheterization-indications-contraindications-and-complications-in-adults?source=see_linkhttp://www.uptodate.com/contents/pulmonary-artery-catheterization-indications-contraindications-and-complications-in-adults?source=see_linkhttp://www.uptodate.com/contents/treatment-of-severe-hypovolemia-or-hypovolemic-shock-in-adults?source=see_linkhttp://www.uptodate.com/contents/treatment-of-severe-hypovolemia-or-hypovolemic-shock-in-adults?source=see_linkhttp://www.uptodate.com/contents/evaluation-and-management-of-severe-sepsis-and-septic-shock-in-adults/abstract/18-20http://www.uptodate.com/contents/evaluation-and-management-of-severe-sepsis-and-septic-shock-in-adults/abstract/18http://www.uptodate.com/contents/evaluation-and-management-of-severe-sepsis-and-septic-shock-in-adults/abstract/19,20http://www.uptodate.com/contents/evaluation-and-management-of-severe-sepsis-and-septic-shock-in-adults#H465648352http://www.uptodate.com/contents/evaluation-and-management-of-severe-sepsis-and-septic-shock-in-adults/abstract/9http://www.uptodate.com/contents/furosemide-drug-information?source=see_linkhttp://www.uptodate.com/contents/evaluation-and-management-of-severe-sepsis-and-septic-shock-in-adults/abstract/26http://www.uptodate.com/contents/evaluation-and-management-of-severe-sepsis-and-septic-shock-in-adults/abstract/27,28http://www.uptodate.com/contents/acute-respiratory-distress-syndrome-supportive-care-and-oxygenation-in-adults?source=see_link&sectionName=Fluid+management&anchor=H15#H15http://www.uptodate.com/contents/acute-respiratory-distress-syndrome-supportive-care-and-oxygenation-in-adults?source=see_link&sectionName=Fluid+management&anchor=H15#H15http://www.uptodate.com/contents/pentastarch-drug-information?source=see_linkhttp://www.uptodate.com/contents/evaluation-and-management-of-severe-sepsis-and-septic-shock-in-adults/abstract/29-35


4/30

3Crystalloi# %ers!s alb!)in* +n the Saline versus 8lbumin Jluid &valuation -S8J&2 trial, 644?

critically ill patients #ere randomly assigned to receive ( percent albumin solution or normal saline

for up to )A days $)4%. There #ere no differences bet#een groups for any endpoint, including the

primary endpoint, mortality. 8mong the patients #ith severe sepsis -1A percent of the total group2,

there #ere also no differences in outcome. +n another multicenter open*label randomized trial of

patients #ith severe sepsis or septic shock, the addition of albumin to crystalloid did not improvesurvival compared to crystalloid alone -E1 versus E) percent2 $E!%.

3Crystalloi# %ers!s 'y#ro+yet'yl star&'* +n the Scandinavian Starch for Severe Sepsis and

Septic Shock -6S2 trial, A!( patients #ith severe sepsis #ere randomly assigned to receive either 6

percent hydro'yethyl starch or 5ingerLs acetate at a volume of up to EE mDCkg of ideal body #eight

per day $E1%. Bhen assessed 4! days after randomization, mortality #as increased in the

hydro'yethyl starch group -1 versus (E percent2 and more patients in the hydro'yethyl starch

group had reuired renal replacement therapy at some time during their illness -)) versus 16

percent2.

3Crystalloi# %ers!s pentastarch* The &fficacy of Golume Substitution and +nsulin Therapy in

Severe Sepsis -G+S&02 trial compared pentastarch to modified 5inger:s lactate in patients #ith

severe sepsis and found no difference in )A*day mortality $E)%. The trial #as stopped early because

there #as a trend to#ard increased 4!*day mortality among patients #ho received pentastarch.

+n our clinical practice, #e generally use a crystalloid solution instead of albumin solution because of the

lack of clear benefit and higher cost of albumin. Be believe that giving a sufficient uantity of intravenous

fluids rapidly and targeting appropriate goals is more important than the type of fluid chosen. Be do not

use hydro'yethyl starch or pentastarch. These choices are consistent #ith the Society of ritical are

9edicineguidelines $4%. -See Treatment of severe hypovolemia or hypovolemic shock in adults, section

on :hoice of replacement fluid:.2

(asopressors — Gasopressors are second line agents in the treatment of severe sepsis and septic

shockK #e prefer intravenous fluids as long as they increase perfusion #ithout seriously impairing gas

e'change $E6%. ;o#ever, intravenous vasopressors are useful in patients #ho remain hypotensive despite

adeuate fluid resuscitation or #ho develop cardiogenic pulmonary edema.

+n most patients #ith severe septic shock, #e prefer to use norepinephrine -table E2 $?,4,E?%. ;o#ever, #e

find phenylephrine -a pure alpha*adrenergic agonist2 to be useful #hen tachycardia or arrhythmias

preclude the use of agents #ith beta*adrenergic activity -eg, norepinephrine2. hoosing a vasopressor

agent is discussed in greater detail else#here. -See "se of vasopressors and inotropes, section on

:hoice of agent in septic shock:.2

A##itional t'erapies — There is conflicting evidence on the use of additional therapies, such as

inotropic therapy or red blood cell transfusion. Such therapies are targeted at increasing the cardiac

output to improve tissue perfusion and thereby raise the central venous -superior vena cava2o'yhemoglobin saturation to#ard normal -ScvO) F?! percent2. Be prefer that their use be limited to those

#ith refractory shock in #hom the ScvO) remains >?! percent after optimization of intravenous fluid and

vasopressor therapy.

Inotropi& t'erapy — 8 trial of inotropic therapy may be #arranted in patients #ho have refractory shock

#ho also have diminished cardiac output $?,A,1A,EA,E4%. +notropic therapy should not be used to increase

the cardiac inde' to supranormal levels $?%. obutamine is the usual inotropic agent $4%. 8t lo# doses,

dobutamine may cause the blood pressure to decrease because its peripheral effects can dilate the

http://www.uptodate.com/contents/albumin-solution-drug-information?source=see_linkhttp://www.uptodate.com/contents/albumin-solution-drug-information?source=see_linkhttp://www.uptodate.com/contents/evaluation-and-management-of-severe-sepsis-and-septic-shock-in-adults/abstract/29http://www.uptodate.com/contents/evaluation-and-management-of-severe-sepsis-and-septic-shock-in-adults/abstract/30http://www.uptodate.com/contents/evaluation-and-management-of-severe-sepsis-and-septic-shock-in-adults/abstract/30http://www.uptodate.com/contents/evaluation-and-management-of-severe-sepsis-and-septic-shock-in-adults/abstract/31http://www.uptodate.com/contents/pentastarch-drug-information?source=see_linkhttp://www.uptodate.com/contents/evaluation-and-management-of-severe-sepsis-and-septic-shock-in-adults/abstract/32http://www.uptodate.com/contents/evaluation-and-management-of-severe-sepsis-and-septic-shock-in-adults/abstract/32http://www.uptodate.com/contents/albumin-solution-drug-information?source=see_linkhttp://www.uptodate.com/contents/albumin-solution-drug-information?source=see_linkhttp://www.uptodate.com/contents/albumin-solution-drug-information?source=see_linkhttp://www.uptodate.com/contents/pentastarch-drug-information?source=see_linkhttp://www.uptodate.com/contents/pentastarch-drug-information?source=see_linkhttp://www.sccm.org/Documents/SSC-Guidelines.pdfhttp://www.sccm.org/Documents/SSC-Guidelines.pdfhttp://www.uptodate.com/contents/evaluation-and-management-of-severe-sepsis-and-septic-shock-in-adults/abstract/9http://www.uptodate.com/contents/evaluation-and-management-of-severe-sepsis-and-septic-shock-in-adults/abstract/9http://www.uptodate.com/contents/treatment-of-severe-hypovolemia-or-hypovolemic-shock-in-adults?source=see_link&sectionName=CHOICE+OF+REPLACEMENT+FLUID&anchor=H4#H4http://www.uptodate.com/contents/treatment-of-severe-hypovolemia-or-hypovolemic-shock-in-adults?source=see_link&sectionName=CHOICE+OF+REPLACEMENT+FLUID&anchor=H4#H4http://www.uptodate.com/contents/evaluation-and-management-of-severe-sepsis-and-septic-shock-in-adults/abstract/36http://www.uptodate.com/contents/norepinephrine-noradrenaline-drug-information?source=see_linkhttp://www.uptodate.com/contents/norepinephrine-noradrenaline-drug-information?source=see_linkhttp://www.uptodate.com/contents/norepinephrine-noradrenaline-drug-information?source=see_linkhttp://www.uptodate.com/content-not-availablehttp://www.uptodate.com/contents/evaluation-and-management-of-severe-sepsis-and-septic-shock-in-adults/abstract/7,9,37http://www.uptodate.com/contents/evaluation-and-management-of-severe-sepsis-and-septic-shock-in-adults/abstract/7,9,37http://www.uptodate.com/contents/evaluation-and-management-of-severe-sepsis-and-septic-shock-in-adults/abstract/7,9,37http://www.uptodate.com/contents/phenylephrine-drug-information?source=see_linkhttp://www.uptodate.com/contents/use-of-vasopressors-and-inotropes?source=see_link&sectionName=Choice+of+agent+in+septic+shock&anchor=H35#H35http://www.uptodate.com/contents/use-of-vasopressors-and-inotropes?source=see_link&sectionName=Choice+of+agent+in+septic+shock&anchor=H35#H35http://www.uptodate.com/contents/use-of-vasopressors-and-inotropes?source=see_link&sectionName=Choice+of+agent+in+septic+shock&anchor=H35#H35http://www.uptodate.com/contents/use-of-vasopressors-and-inotropes?source=see_link&sectionName=Choice+of+agent+in+septic+shock&anchor=H35#H35http://www.uptodate.com/contents/evaluation-and-management-of-severe-sepsis-and-septic-shock-in-adults/abstract/7,8,18,38,39http://www.uptodate.com/contents/evaluation-and-management-of-severe-sepsis-and-septic-shock-in-adults/abstract/7,8,18,38,39http://www.uptodate.com/contents/evaluation-and-management-of-severe-sepsis-and-septic-shock-in-adults/abstract/7http://www.uptodate.com/contents/dobutamine-drug-information?source=see_linkhttp://www.uptodate.com/contents/evaluation-and-management-of-severe-sepsis-and-septic-shock-in-adults/abstract/9http://www.uptodate.com/contents/evaluation-and-management-of-severe-sepsis-and-septic-shock-in-adults/abstract/9http://www.uptodate.com/contents/albumin-solution-drug-information?source=see_linkhttp://www.uptodate.com/contents/evaluation-and-management-of-severe-sepsis-and-septic-shock-in-adults/abstract/29http://www.uptodate.com/contents/evaluation-and-management-of-severe-sepsis-and-septic-shock-in-adults/abstract/30http://www.uptodate.com/contents/evaluation-and-management-of-severe-sepsis-and-septic-shock-in-adults/abstract/31http://www.uptodate.com/contents/pentastarch-drug-information?source=see_linkhttp://www.uptodate.com/contents/evaluation-and-management-of-severe-sepsis-and-septic-shock-in-adults/abstract/32http://www.uptodate.com/contents/albumin-solution-drug-information?source=see_linkhttp://www.uptodate.com/contents/pentastarch-drug-information?source=see_linkhttp://www.sccm.org/Documents/SSC-Guidelines.pdfhttp://www.sccm.org/Documents/SSC-Guidelines.pdfhttp://www.uptodate.com/contents/evaluation-and-management-of-severe-sepsis-and-septic-shock-in-adults/abstract/9http://www.uptodate.com/contents/treatment-of-severe-hypovolemia-or-hypovolemic-shock-in-adults?source=see_link&sectionName=CHOICE+OF+REPLACEMENT+FLUID&anchor=H4#H4http://www.uptodate.com/contents/treatment-of-severe-hypovolemia-or-hypovolemic-shock-in-adults?source=see_link&sectionName=CHOICE+OF+REPLACEMENT+FLUID&anchor=H4#H4http://www.uptodate.com/contents/evaluation-and-management-of-severe-sepsis-and-septic-shock-in-adults/abstract/36http://www.uptodate.com/contents/norepinephrine-noradrenaline-drug-information?source=see_linkhttp://www.uptodate.com/content-not-availablehttp://www.uptodate.com/contents/evaluation-and-management-of-severe-sepsis-and-septic-shock-in-adults/abstract/7,9,37http://www.uptodate.com/contents/phenylephrine-drug-information?source=see_linkhttp://www.uptodate.com/contents/use-of-vasopressors-and-inotropes?source=see_link&sectionName=Choice+of+agent+in+septic+shock&anchor=H35#H35http://www.uptodate.com/contents/use-of-vasopressors-and-inotropes?source=see_link&sectionName=Choice+of+agent+in+septic+shock&anchor=H35#H35http://www.uptodate.com/contents/evaluation-and-management-of-severe-sepsis-and-septic-shock-in-adults/abstract/7,8,18,38,39http://www.uptodate.com/contents/evaluation-and-management-of-severe-sepsis-and-septic-shock-in-adults/abstract/7http://www.uptodate.com/contents/dobutamine-drug-information?source=see_linkhttp://www.uptodate.com/contents/evaluation-and-management-of-severe-sepsis-and-septic-shock-in-adults/abstract/9


5/30

systemic arteries. ;o#ever, as the dose is increased, blood pressure usually rises because cardiac

output increases out of proportion to the fall in peripheral vascular resistance. -See "se of vasopressors

and inotropes, section on :obutamine:.2

Re# bloo# &ell trans!sions — =ased upon clinical e'perience, randomized studies, and guidelines on

transfusion of blood products in critically ill patients, #e typically reserve red blood cell transfusion for

patients #ith a hemoglobin level M? g per deciliter. &'ceptions include suspicion of concurrent

hemorrhagic shock or active myocardial ischemia.

Support for a restrictive transfusion strategy -goal hemoglobin @? gCdD2 is derived from direct and

indirect evidence from randomized studies of patients #ith septic shock/

NOne multicenter randomized study of 44A patients #ith septic shock reported no difference in

)A day mortality bet#een patients #ho #ere transfused #hen the hemoglobin #as

M? gCdD-restrictive strategy2 and patients #ho #ere transfused #hen the hemoglobin #as

M4 gCdD -liberal strategy2 $(!%. The restrictive strategy resulted in ! percent fe#er red blood

cell transfusions -1( versus E!AA transfusions2 and did not have any adverse effect on the

rate of ischemic events -? versus A percent2.

Nata from randomized studies of early goal directed therapy -&HT2 that use red blood cell

transfusion as part of the protocol for treating patients #ith sepsis are conflicting. Bhile one

trial initially reported a mortality benefit from &HT that included transfusing patients to a goal

hematocrit @E! -hemoglobin level 1! gCdD2 $1A%, t#o similarly designed studies published since

then reported no benefit to this strategy $14,)!%. These studies are discussed belo#.

-See:0rotocol*directed therapy: belo#.2

+n further support of a restrictive approach to transfusion in patients #ith septic shock is the

consensus among e'perts that transfusing to a goal of @? gCdD is also preferred in critically ill

patients #ithout sepsis $(1*(E%. The use of blood transfusions in critically*ill patients is discussed in

detail separately. -See "se of blood products in the critically ill, section on :5ed blood cells: .2

Goals o initial res!s&itation — The goal of fluid resuscitation is early restoration of perfusion to preventor limit multiple organ dysfunction, as #ell as to reduce mortality.

The term early goal*directed therapy -&HT2 refers to the administration of intravenous fluids #ithin t'e

irst si+ 'o!rs o presentation using physiologic targets to guide fluid management. &HT has gained

#idespread acceptance in clinical practice but the optimal targets are unkno#n.

Early "oal$#ire&te# t'erapy tar"ets — 8lthough evidence is conflicting regarding the routine

measurement of early goal*directed therapy targets, #e suggest measuring the follo#ing targets for fluid

management in patients #ith sepsis/

39ean arterial pressure -9802 F6 mm;g -980 $-) ' diastolic2 P systolic%CE2 -calculator 12

3"rine output F!. mDCkgChour 3Static or dynamic predictors of fluid responsiveness, eg, central venous pressure -G02 A to 1)

mm;g #hen central access is available -static measurement2 or respiratory changes in the radial

artery pulse pressure -dynamic measurement2.

3entral venous -superior vena cava2 o'yhemoglobin saturation -ScvO)2 F?! percent -#hen central

access is available2 or mi'ed venous o'yhemoglobin saturation -SvO )2 F6 percent -if a pulmonary

artery catheter is being used2.

http://www.uptodate.com/contents/use-of-vasopressors-and-inotropes?source=see_link&sectionName=Dobutamine&anchor=H21#H21http://www.uptodate.com/contents/use-of-vasopressors-and-inotropes?source=see_link&sectionName=Dobutamine&anchor=H21#H21http://www.uptodate.com/contents/evaluation-and-management-of-severe-sepsis-and-septic-shock-in-adults/abstract/40http://www.uptodate.com/contents/evaluation-and-management-of-severe-sepsis-and-septic-shock-in-adults/abstract/18http://www.uptodate.com/contents/evaluation-and-management-of-severe-sepsis-and-septic-shock-in-adults/abstract/18http://www.uptodate.com/contents/evaluation-and-management-of-severe-sepsis-and-septic-shock-in-adults/abstract/19,20http://www.uptodate.com/contents/evaluation-and-management-of-severe-sepsis-and-septic-shock-in-adults/abstract/19,20http://www.uptodate.com/contents/evaluation-and-management-of-severe-sepsis-and-septic-shock-in-adults#H465648396http://www.uptodate.com/contents/evaluation-and-management-of-severe-sepsis-and-septic-shock-in-adults/abstract/41-43http://www.uptodate.com/contents/evaluation-and-management-of-severe-sepsis-and-septic-shock-in-adults/abstract/41-43http://www.uptodate.com/contents/use-of-blood-products-in-the-critically-ill?source=see_link&sectionName=RED+BLOOD+CELLS&anchor=H2#H2http://www.uptodate.com/contents/use-of-blood-products-in-the-critically-ill?source=see_link&sectionName=RED+BLOOD+CELLS&anchor=H2#H2http://www.uptodate.com/contents/calculator-mean-arterial-pressure-map?source=see_linkhttp://www.uptodate.com/contents/use-of-vasopressors-and-inotropes?source=see_link&sectionName=Dobutamine&anchor=H21#H21http://www.uptodate.com/contents/use-of-vasopressors-and-inotropes?source=see_link&sectionName=Dobutamine&anchor=H21#H21http://www.uptodate.com/contents/evaluation-and-management-of-severe-sepsis-and-septic-shock-in-adults/abstract/40http://www.uptodate.com/contents/evaluation-and-management-of-severe-sepsis-and-septic-shock-in-adults/abstract/18http://www.uptodate.com/contents/evaluation-and-management-of-severe-sepsis-and-septic-shock-in-adults/abstract/19,20http://www.uptodate.com/contents/evaluation-and-management-of-severe-sepsis-and-septic-shock-in-adults#H465648396http://www.uptodate.com/contents/evaluation-and-management-of-severe-sepsis-and-septic-shock-in-adults/abstract/41-43http://www.uptodate.com/contents/use-of-blood-products-in-the-critically-ill?source=see_link&sectionName=RED+BLOOD+CELLS&anchor=H2#H2http://www.uptodate.com/contents/calculator-mean-arterial-pressure-map?source=see_link


6/30

Dactate clearance is not readily available at the bedside, making it a less useful target to follo# acutely in

&HT. 7onetheless, it should be follo#ed as a target in patients #ith sepsis to ensure a trend that

demonstrates adeuate clearance #ith therapy.

The optimal physiologic target-s2 of &HT is unkno#n. There is also conflicting evidence on the value of

measuring such targets, particularly G0 and ScGO), #hich reuire central catheter placement $1A*

)!,((%. +n addition, the generalizability of a standard targeted approach to both resource*poor and

resource*rich facilities is unkno#n. Be prefer measuring 980 and urine output as universal targets that

can be readily measured in all patients #ith sepsis, #ith the addition of G0 andCor ScGO) in those in

#hom central access is other#ise reuired. This approach differs slightly from that of The Surviving

Sepsis ampaignguidelines that recommend central venous access for G0CScvO) measurement

together #ith 980 and urine output in all patients #ith severe sepsis $ 4%. ;o#ever, these guidelines #ere

created before the results of three maIor randomized trials -0ro&SS, 85+S&, 0ro9+Se2, that sho#ed no

mortality benefit to an &HT*based approach, #ere published $14,)!,((,(%.

&vidence that supports the use of &HT targets is described belo#/

3C(P, MAP an# !rine o!tp!t < G0 A to 1) mm;g, 980 F6 mm;g - calculator 12, and urineoutput F!. mDCkg per hour are common &HT targets used in clinical practice. Support for their use

is derived from clinical e'perience and their use in the single randomized trial that studied them #ith

and #ithout ScvO) $1A%. They have not been compared to each other nor have they been proven to

be superior to any other target or to clinical assessment.

The ideal targets for 980, G0, and urine output are unkno#n. One trial that randomized patients to

a target 980 of 6 to ?! mm;g -lo# target 9802 or A! to A mm;g -high target 9802 reported no

mortality benefit to targeting a higher 980 $(6%. 0atients #ith a higher 980 had a greater incidence

of atrial fibrillation -? versus E percent2, suggesting that targeting a 980 @A! mm;g is potentially

harmful.

3S&%O- < &vidence from randomized trials that study the value of central venous o'yhemoglobin

saturation -ScvO)2 report mi'ed results. Bhile one early trial of patients #ith septic shock reported amortality benefit to targeting ScvO) F?! percent in a protocol*based therapy, trials published since

then -0ro&SS, 85+S&, 0ro9+Se2 have reported no mortality benefit $1A*)!,((%. -See :0rotocol*

directed therapy: belo#.2

3La&tate &learan&e < 8lthough the optimal freuency is unkno#n, #e follo# serum lactate -eg,

every si' hours2, as an additional &HT target in patients #ith sepsis until the lactate value has

clearly fallen.

The lactate clearance is defined by the euation $-initial lactate * lactate @) hours later2Cinitial lactate%

' 1!!. The lactate clearance and interval change in lactate over the first 1) hours of resuscitation

has been evaluated as a potential marker for effective resuscitation $ (?,(A%. One trial randomly

assigned E!! patients #ith severe sepsis to undergo resuscitation targeting either a lactate

clearance F1! percent or an ScvO) F?! percent -other than these targets, the resuscitation protocols

that included 980, G0, and urine output targets #ere identical2 $(?%. There #as no difference in

hospital mortality, length of stay, ventilator*free days, or incidence of multiorgan failure, suggesting

that lactate clearance criteria may be an acceptable alternative to ScvO) criteria.

8fter the restoration of perfusion, lactate is a poor marker of tissue perfusion $(4%. 8s a result, lactate

values are generally unhelpful follo#ing restoration of perfusion, #ith one e'ception < a rising lactate

http://www.uptodate.com/contents/evaluation-and-management-of-severe-sepsis-and-septic-shock-in-adults/abstract/18-20,44http://www.uptodate.com/contents/evaluation-and-management-of-severe-sepsis-and-septic-shock-in-adults/abstract/18-20,44http://www.sccm.org/Documents/SSC-Guidelines.pdfhttp://www.sccm.org/Documents/SSC-Guidelines.pdfhttp://www.sccm.org/Documents/SSC-Guidelines.pdfhttp://www.uptodate.com/contents/evaluation-and-management-of-severe-sepsis-and-septic-shock-in-adults/abstract/9http://www.uptodate.com/contents/evaluation-and-management-of-severe-sepsis-and-septic-shock-in-adults/abstract/9http://www.uptodate.com/contents/evaluation-and-management-of-severe-sepsis-and-septic-shock-in-adults/abstract/19,20,44,45http://www.uptodate.com/contents/calculator-mean-arterial-pressure-map?source=see_linkhttp://www.uptodate.com/contents/evaluation-and-management-of-severe-sepsis-and-septic-shock-in-adults/abstract/18http://www.uptodate.com/contents/evaluation-and-management-of-severe-sepsis-and-septic-shock-in-adults/abstract/18http://www.uptodate.com/contents/evaluation-and-management-of-severe-sepsis-and-septic-shock-in-adults/abstract/46http://www.uptodate.com/contents/evaluation-and-management-of-severe-sepsis-and-septic-shock-in-adults/abstract/18-20,44http://www.uptodate.com/contents/evaluation-and-management-of-severe-sepsis-and-septic-shock-in-adults#H465648396http://www.uptodate.com/contents/evaluation-and-management-of-severe-sepsis-and-septic-shock-in-adults#H465648396http://www.uptodate.com/contents/evaluation-and-management-of-severe-sepsis-and-septic-shock-in-adults/abstract/47,48http://www.uptodate.com/contents/evaluation-and-management-of-severe-sepsis-and-septic-shock-in-adults/abstract/47http://www.uptodate.com/contents/evaluation-and-management-of-severe-sepsis-and-septic-shock-in-adults/abstract/49http://www.uptodate.com/contents/evaluation-and-management-of-severe-sepsis-and-septic-shock-in-adults/abstract/18-20,44http://www.uptodate.com/contents/evaluation-and-management-of-severe-sepsis-and-septic-shock-in-adults/abstract/18-20,44http://www.sccm.org/Documents/SSC-Guidelines.pdfhttp://www.sccm.org/Documents/SSC-Guidelines.pdfhttp://www.uptodate.com/contents/evaluation-and-management-of-severe-sepsis-and-septic-shock-in-adults/abstract/9http://www.uptodate.com/contents/evaluation-and-management-of-severe-sepsis-and-septic-shock-in-adults/abstract/19,20,44,45http://www.uptodate.com/contents/calculator-mean-arterial-pressure-map?source=see_linkhttp://www.uptodate.com/contents/evaluation-and-management-of-severe-sepsis-and-septic-shock-in-adults/abstract/18http://www.uptodate.com/contents/evaluation-and-management-of-severe-sepsis-and-septic-shock-in-adults/abstract/46http://www.uptodate.com/contents/evaluation-and-management-of-severe-sepsis-and-septic-shock-in-adults/abstract/18-20,44http://www.uptodate.com/contents/evaluation-and-management-of-severe-sepsis-and-septic-shock-in-adults#H465648396http://www.uptodate.com/contents/evaluation-and-management-of-severe-sepsis-and-septic-shock-in-adults#H465648396http://www.uptodate.com/contents/evaluation-and-management-of-severe-sepsis-and-septic-shock-in-adults/abstract/47,48http://www.uptodate.com/contents/evaluation-and-management-of-severe-sepsis-and-septic-shock-in-adults/abstract/47http://www.uptodate.com/contents/evaluation-and-management-of-severe-sepsis-and-septic-shock-in-adults/abstract/49


7/30

level should prompt reevaluation of perfusion -see Genous blood gases and other alternatives to

arterial blood gases2.

3Ot'er < ynamic indices have been studied as a potential target to guide fluid management in

sepsis. 5espiratory changes in the vena caval diameter, radial artery pulse pressure, aortic blood

flo# peak velocity, and brachial artery blood flo# velocity are considered dynamic hemodynamic

measures, #hereas G0, 980, ScvO) and pulmonary artery occlusion pressure are consideredstatic hemodynamic measures $!,1%. There is increasing evidence that dynamic measures are

more accurate predictors of fluid responsiveness than static measures, as long as the patients are in

sinus rhythm and passively ventilated #ith a sufficient tidal volume $)1,),E%. Jor actively breathing

patients or those #ith irregular cardiac rhythms, an increase in the cardiac output in response to a

passive leg*raising maneuver -measured by echocardiography, arterial pulse #aveform analysis, or

pulmonary artery catheterization2 is a sensitive and specific predictor of fluid responsiveness $ (%.

Darge randomized studies #ill be needed proving the efficacy of assessing dynamic measurement in

response to intravenous fluids before they can be routinely applied to patients for the management

of sepsis.

Proto&ol$#ire&te# t'erapy — 0rotocols targeted at the use of a combination of physiologic endpoints toguide fluid management in patients #ith severe sepsis and septic shock are common practice $ 1A*

)!,((,(,*?%. Typically, they combine the &HT targets -ScvO), G0, 980 -calculator 12 and urine

output, lactate2 for fluid management #ith early administration of antibiotics, both #ithin the first si' hours

of presentation.

There is conflicting evidence regarding the value of protocol*based therapy for sepsis $1A*)!,((,(,?*

4%/

3One single center randomized trial of )6E patients #ith severe sepsis or septic shock compared a

protocol that included targeting ScvO) F?! percent, G0 A to 1) mm;g, 980 F6 mm;g, and urine

output F!. mDCkgChour to conventional therapy that targeted G0, 980, and urine output only $1A%.

=oth groups initiated therapy -including antibiotics2 #ithin si' hours of presentation. 9ortality #aslo#er in the group #here all four targets #ere used -E1 versus (? percent2, suggesting that targeting

ScvO), G0, 980, and urine output #as a superior strategy. There #as a heavy emphasis on the

use of red cell transfusion -for a hematocrit @E!2 and dobutamine in order to reach the ScvO) target

in this trial. +n addition, the results of this trial may not be generalizable due to the inclusion of a

significant number of sick patients #ith liver and heart disease that may have potentially biased the

outcome favorably.

38 multicenter randomized trial -0ro&SS2 of 1E(1 patients #ith septic shock reported no mortality

benefit #ith protocol*based therapies $14%. 8 protocol*based therapy that used all of the &HT

targets -ScvO), G0, 980 and urine outputK protocol*based &HTK central access reuired2 #as

compared to a protocol that used some of the &HT targets -980 and urine outputK protocol*based

standard therapyK central access not reuired2 and to usual care -no protocol used to direct fluid

management2. There #ere no differences in 6!*day mortality bet#een the groups -)1 versus 1A

versus 14 percent2.

T#o similarly designed multicenter randomized trials of 16!! -85+S&2 and )16! -0ro9+Se2 patients

#ith septic shock also reported no mortality benefit from &HT $ )!,((%. +n 85+S&, compared to

usual care, the 4! day mortality of 14 percent #as similar in patients #ho received &HT using the

http://www.uptodate.com/contents/venous-blood-gases-and-other-alternatives-to-arterial-blood-gases?source=see_linkhttp://www.uptodate.com/contents/venous-blood-gases-and-other-alternatives-to-arterial-blood-gases?source=see_linkhttp://www.uptodate.com/contents/evaluation-and-management-of-severe-sepsis-and-septic-shock-in-adults/abstract/50,51http://www.uptodate.com/contents/evaluation-and-management-of-severe-sepsis-and-septic-shock-in-adults/abstract/21,52,53http://www.uptodate.com/contents/evaluation-and-management-of-severe-sepsis-and-septic-shock-in-adults/abstract/21,52,53http://www.uptodate.com/contents/evaluation-and-management-of-severe-sepsis-and-septic-shock-in-adults/abstract/54http://www.uptodate.com/contents/evaluation-and-management-of-severe-sepsis-and-septic-shock-in-adults/abstract/54http://www.uptodate.com/contents/evaluation-and-management-of-severe-sepsis-and-septic-shock-in-adults/abstract/18-20,44,45,55-57http://www.uptodate.com/contents/evaluation-and-management-of-severe-sepsis-and-septic-shock-in-adults/abstract/18-20,44,45,55-57http://www.uptodate.com/contents/evaluation-and-management-of-severe-sepsis-and-septic-shock-in-adults/abstract/18-20,44,45,55-57http://www.uptodate.com/contents/calculator-mean-arterial-pressure-map?source=see_linkhttp://www.uptodate.com/contents/evaluation-and-management-of-severe-sepsis-and-septic-shock-in-adults/abstract/18-20,44,45,57-59http://www.uptodate.com/contents/evaluation-and-management-of-severe-sepsis-and-septic-shock-in-adults/abstract/18-20,44,45,57-59http://www.uptodate.com/contents/evaluation-and-management-of-severe-sepsis-and-septic-shock-in-adults/abstract/18http://www.uptodate.com/contents/evaluation-and-management-of-severe-sepsis-and-septic-shock-in-adults/abstract/18http://www.uptodate.com/contents/dobutamine-drug-information?source=see_linkhttp://www.uptodate.com/contents/dobutamine-drug-information?source=see_linkhttp://www.uptodate.com/contents/evaluation-and-management-of-severe-sepsis-and-septic-shock-in-adults/abstract/19http://www.uptodate.com/contents/evaluation-and-management-of-severe-sepsis-and-septic-shock-in-adults/abstract/19http://www.uptodate.com/contents/evaluation-and-management-of-severe-sepsis-and-septic-shock-in-adults/abstract/20,44http://www.uptodate.com/contents/evaluation-and-management-of-severe-sepsis-and-septic-shock-in-adults/abstract/20,44http://www.uptodate.com/contents/venous-blood-gases-and-other-alternatives-to-arterial-blood-gases?source=see_linkhttp://www.uptodate.com/contents/venous-blood-gases-and-other-alternatives-to-arterial-blood-gases?source=see_linkhttp://www.uptodate.com/contents/evaluation-and-management-of-severe-sepsis-and-septic-shock-in-adults/abstract/50,51http://www.uptodate.com/contents/evaluation-and-management-of-severe-sepsis-and-septic-shock-in-adults/abstract/21,52,53http://www.uptodate.com/contents/evaluation-and-management-of-severe-sepsis-and-septic-shock-in-adults/abstract/54http://www.uptodate.com/contents/evaluation-and-management-of-severe-sepsis-and-septic-shock-in-adults/abstract/18-20,44,45,55-57http://www.uptodate.com/contents/evaluation-and-management-of-severe-sepsis-and-septic-shock-in-adults/abstract/18-20,44,45,55-57http://www.uptodate.com/contents/calculator-mean-arterial-pressure-map?source=see_linkhttp://www.uptodate.com/contents/evaluation-and-management-of-severe-sepsis-and-septic-shock-in-adults/abstract/18-20,44,45,57-59http://www.uptodate.com/contents/evaluation-and-management-of-severe-sepsis-and-septic-shock-in-adults/abstract/18-20,44,45,57-59http://www.uptodate.com/contents/evaluation-and-management-of-severe-sepsis-and-septic-shock-in-adults/abstract/18http://www.uptodate.com/contents/dobutamine-drug-information?source=see_linkhttp://www.uptodate.com/contents/evaluation-and-management-of-severe-sepsis-and-septic-shock-in-adults/abstract/19http://www.uptodate.com/contents/evaluation-and-management-of-severe-sepsis-and-septic-shock-in-adults/abstract/20,44


8/30

traditional targets outlined in prior studies $)!%. Similarly, in 0ro9+Se, the 4! day mortality #as no

different -)4 percent2 bet#een the &HT and usual care groups $((%.

One e'planation for the apparent negative results from these three trials may be that central line

placement #as common -@! percent2 in patients receiving protocol*based standard therapy and

usual careK it is likely that G0 and ScvO) #ere measured and targeted in these patients as #ell.

Dack of benefit may also be attributed to overall better outcomes in these studies, perhaps due toearly administration of antibiotics -?! to 1!! percent before randomization2 in all groups, and to

improved clinical performance by highly trained clinicians in academic centers during an era that

follo#s an aggressive sepsis education and management campaign.

Ti)in" an# #!ration — The early administration of fluid appears to be more important than volume or

type of fluid in reducing mortality associated #ith sepsis. =ased upon evidence from randomized studies

and meta*analyses, #e favor the initiation of fluid resuscitation #ithin si+ hours of presentation. Once the

targets of resuscitation are met and perfusion is restored, fluids can be reduced or stopped, and

occasionally patients can be diuresed, #hen necessary. 5esolution of severe sepsis and septic shock can

take as little as a fe# hours or can be protracted to days or #eeks.

8 )!!A meta*analysis of randomized trials that initiated resuscitation targeting specific physiologic

endpoints reported that compared to standard care, only trials that initiated resuscitation #ithin )( hours

of the onset of sepsis sho#ed a mortality benefit -E4 versus ? percent, odds ratio !.!, 4Q + !.E?*

!.642 $6!%. +n contrast, analysis of randomized trials that initiated therapy more than )( hours after the

onset of sepsis found no difference in mortality -6( versus A percent for standard resuscitation, odds

ratio 1.16, 4Q + !.6!*).))2.

There are t#o possible outcomes follo#ing the interventions described above/

3Ina#e.!ate per!sion < espite aggressive therapy, the patient may have persistent

hypoperfusion and progressive organ failure. This should prompt reassessment of the adeuacy of

the above therapies, antimicrobial regimen, and control of the septic focus, as #ell as the accuracy

of the diagnosis and the possibility that une'pected complications or coe'isting problems have

intervened -eg, pneumothora' follo#ing G insertion2.

3A#e.!ate per!sion < 0atients #ho respond to therapy should have the rate of fluid

administration reduced or stopped, and vasopressor support #eaned. 0atients should also continue

to have their clinical and laboratory parameters follo#ed closely. These include blood pressure,

arterial lactate, urine output, creatinine, platelet count, Hlasgo# coma scale score, serum bilirubin,

liver enzymes, o'ygenation -ie, arterial o'ygen tension or o'yhemoglobin saturation2, and gut

function -table (2. 5eevaluation is indicated if any of these parameters #orsen or fail to improve.

CONTROL O/ THE SEPTIC /OCUS — 0rompt identification and treatment of the primary site or sites of

infection are essential $61*6E%. This is the primary therapeutic intervention, #ith most other interventions

being purely supportive. 8ntibiotics should be administered #ithin the first si' hours of presentation or

earlier.

I#entii&ation o t'e septi& o&!s — 8 careful history and physical e'amination may yield clues to the

source of sepsis and help guide microbiologic evaluation - table 2. 8s an e'ample, sepsis arising after

trauma or surgery is often due to infection at the site of inIury or surgery. The presence of a urinary or

vascular catheter increases the chances that these are the source of sepsis.

http://www.uptodate.com/contents/evaluation-and-management-of-severe-sepsis-and-septic-shock-in-adults/abstract/20http://www.uptodate.com/contents/evaluation-and-management-of-severe-sepsis-and-septic-shock-in-adults/abstract/44http://www.uptodate.com/contents/evaluation-and-management-of-severe-sepsis-and-septic-shock-in-adults/abstract/60http://www.uptodate.com/contents/evaluation-and-management-of-severe-sepsis-and-septic-shock-in-adults/abstract/60http://www.uptodate.com/content-not-availablehttp://www.uptodate.com/contents/evaluation-and-management-of-severe-sepsis-and-septic-shock-in-adults/abstract/61-63http://www.uptodate.com/contents/evaluation-and-management-of-severe-sepsis-and-septic-shock-in-adults/abstract/61-63http://www.uptodate.com/content-not-availablehttp://www.uptodate.com/contents/evaluation-and-management-of-severe-sepsis-and-septic-shock-in-adults/abstract/20http://www.uptodate.com/contents/evaluation-and-management-of-severe-sepsis-and-septic-shock-in-adults/abstract/44http://www.uptodate.com/contents/evaluation-and-management-of-severe-sepsis-and-septic-shock-in-adults/abstract/60http://www.uptodate.com/content-not-availablehttp://www.uptodate.com/contents/evaluation-and-management-of-severe-sepsis-and-septic-shock-in-adults/abstract/61-63http://www.uptodate.com/content-not-available


9/30

Hram stain of material from sites of possible infection may give early clues to the etiology of infection

#hile cultures are incubating. 8s e'amples, urine should be routinely analyzed via dipstick for leukocyte

esterase, Hram stained, and culturedK sputum should be e'amined in a patient #ith a productive coughK

and an intra*abdominal collection in a postoperative patient should be percutaneously sampled under

ultrasound or other radiologic guidance.

=lood should be dra#n from t#o distinct venipuncture sites and inoculated into standard blood culture

media -aerobic and anaerobic2. Jor patients #ith a vascular catheter, blood should be obtained both

through the catheter and from another site $4%. -See =lood cultures for the detection of bacteremia.2

+f invasive candida or aspergillus infection is suspected, serologic assays for 1,E beta**glucan,

galactomannan, and anti*mannan antibodies, if available, may provide early evidence of these fungal

infections $4%. The limitations of these assays and their role in the diagnosis of fungal infection are

discussed separately. -See linical manifestations and diagnosis of candidemia and invasive candidiasis

in adults, section on :7on*culture methods: and iagnosis of invasive aspergillosis, section on

:Halactomannan antigen detection: and iagnosis of invasive aspergillosis, section on :=eta**glucan

assay:.2

There is no single test that immediately confirms the diagnosis of severe sepsis or septic shock. ;o#ever,

several laboratory tests, all of #hich are still investigational, have been studied as diagnostic markers of

active bacterial infection $6%/

3&levated serum procalcitonin levels are associated #ith bacterial infection and sepsis $ 6(*66%.

espite this, a meta*analysis of 1A studies found that procalcitonin did not readily distinguish sepsis

from nonseptic systemic inflammation -sensitivity of ?1 percent and specificity of ?1 percent2 $6%. 8n

additional randomized trial and another meta*analysis found that using clinical algorithms based

upon procalcitonin levels did not affect mortality or duration of antibiotic treatment $6?,6A%.

3The plasma concentration of soluble T5&9*1 -triggering receptor e'pressed on myeloid cells2, a

member of the immunoglobulin superfamily that is specifically upregulated in the presence of

bacterial products, is increased in patients #ith sepsis $64*?1%. +n a small trial, increased T5&9*1

levels #ere both sensitive and specific for the diagnosis of bacterial sepsis -46 and A4 percent,

respectively2 $64%. ;o#ever, a subseuent prospective cohort study found that increased T5&9*1

levels predicted sepsis #ith a sensitivity and specificity of only E and A6 percent, respectively $?)%.

Serial monitoring of T5&9*1 may also provide prognostic information in patients #ith established

sepsis $?!,?1%.

3+ncreased e'pression of 6( on polymorphonuclear leukocytes indicates cellular activation and

has been sho#n to occur in patients #ith sepsis $ ?E,?(%. +n a prospective cohort study of E!!

consecutive critically ill patients, increased 6( e'pression predicted sepsis #ith a sensitivity of A(

percent and a specificity of 4 percent $?)%. +n this study, the sensitivity and specificity of increased

6( e'pression #ere superior to that of increased procalcitonin or T5&9*1 levels.

The combination of procalcitonin levels, T5&9*1 levels, and 6( e'pression appears to be superior to

the use of any of these markers alone. ;o#ever, evaluation of the clinical usefulness of such biomarkers

is still in its early stages and should be considered preliminary. "ntil additional clinical investigations have

been performed, #e do not suggest the routine use of such biomarkers to identify sepsis.

Era#i&ation o ine&tion — 0rompt and effective treatment of the active infection is essential to the

successful treatment of severe sepsis and septic shock $4%. Source control -physical measures

http://www.uptodate.com/contents/evaluation-and-management-of-severe-sepsis-and-septic-shock-in-adults/abstract/9http://www.uptodate.com/contents/blood-cultures-for-the-detection-of-bacteremia?source=see_linkhttp://www.uptodate.com/contents/blood-cultures-for-the-detection-of-bacteremia?source=see_linkhttp://www.uptodate.com/contents/evaluation-and-management-of-severe-sepsis-and-septic-shock-in-adults/abstract/9http://www.uptodate.com/contents/clinical-manifestations-and-diagnosis-of-candidemia-and-invasive-candidiasis-in-adults?source=see_link&sectionName=Non-culture+methods&anchor=H7#H7http://www.uptodate.com/contents/clinical-manifestations-and-diagnosis-of-candidemia-and-invasive-candidiasis-in-adults?source=see_link&sectionName=Non-culture+methods&anchor=H7#H7http://www.uptodate.com/contents/diagnosis-of-invasive-aspergillosis?source=see_link&sectionName=Galactomannan+antigen+detection&anchor=H1064486430#H1064486430http://www.uptodate.com/contents/diagnosis-of-invasive-aspergillosis?source=see_link&sectionName=Galactomannan+antigen+detection&anchor=H1064486430#H1064486430http://www.uptodate.com/contents/diagnosis-of-invasive-aspergillosis?source=see_link&sectionName=Beta-D-glucan+assay&anchor=H1064486465#H1064486465http://www.uptodate.com/contents/diagnosis-of-invasive-aspergillosis?source=see_link&sectionName=Beta-D-glucan+assay&anchor=H1064486465#H1064486465http://www.uptodate.com/contents/evaluation-and-management-of-severe-sepsis-and-septic-shock-in-adults/abstract/6http://www.uptodate.com/contents/evaluation-and-management-of-severe-sepsis-and-septic-shock-in-adults/abstract/64-66http://www.uptodate.com/contents/evaluation-and-management-of-severe-sepsis-and-septic-shock-in-adults/abstract/64-66http://www.uptodate.com/contents/evaluation-and-management-of-severe-sepsis-and-septic-shock-in-adults/abstract/65http://www.uptodate.com/contents/evaluation-and-management-of-severe-sepsis-and-septic-shock-in-adults/abstract/67,68http://www.uptodate.com/contents/evaluation-and-management-of-severe-sepsis-and-septic-shock-in-adults/abstract/67,68http://www.uptodate.com/contents/evaluation-and-management-of-severe-sepsis-and-septic-shock-in-adults/abstract/69-71http://www.uptodate.com/contents/evaluation-and-management-of-severe-sepsis-and-septic-shock-in-adults/abstract/69-71http://www.uptodate.com/contents/evaluation-and-management-of-severe-sepsis-and-septic-shock-in-adults/abstract/69http://www.uptodate.com/contents/evaluation-and-management-of-severe-sepsis-and-septic-shock-in-adults/abstract/72http://www.uptodate.com/contents/evaluation-and-management-of-severe-sepsis-and-septic-shock-in-adults/abstract/72http://www.uptodate.com/contents/evaluation-and-management-of-severe-sepsis-and-septic-shock-in-adults/abstract/70,71http://www.uptodate.com/contents/evaluation-and-management-of-severe-sepsis-and-septic-shock-in-adults/abstract/73,74http://www.uptodate.com/contents/evaluation-and-management-of-severe-sepsis-and-septic-shock-in-adults/abstract/72http://www.uptodate.com/contents/evaluation-and-management-of-severe-sepsis-and-septic-shock-in-adults/abstract/72http://www.uptodate.com/contents/evaluation-and-management-of-severe-sepsis-and-septic-shock-in-adults/abstract/9http://www.uptodate.com/contents/evaluation-and-management-of-severe-sepsis-and-septic-shock-in-adults/abstract/9http://www.uptodate.com/contents/evaluation-and-management-of-severe-sepsis-and-septic-shock-in-adults/abstract/9http://www.uptodate.com/contents/blood-cultures-for-the-detection-of-bacteremia?source=see_linkhttp://www.uptodate.com/contents/evaluation-and-management-of-severe-sepsis-and-septic-shock-in-adults/abstract/9http://www.uptodate.com/contents/clinical-manifestations-and-diagnosis-of-candidemia-and-invasive-candidiasis-in-adults?source=see_link&sectionName=Non-culture+methods&anchor=H7#H7http://www.uptodate.com/contents/clinical-manifestations-and-diagnosis-of-candidemia-and-invasive-candidiasis-in-adults?source=see_link&sectionName=Non-culture+methods&anchor=H7#H7http://www.uptodate.com/contents/diagnosis-of-invasive-aspergillosis?source=see_link&sectionName=Galactomannan+antigen+detection&anchor=H1064486430#H1064486430http://www.uptodate.com/contents/diagnosis-of-invasive-aspergillosis?source=see_link&sectionName=Galactomannan+antigen+detection&anchor=H1064486430#H1064486430http://www.uptodate.com/contents/diagnosis-of-invasive-aspergillosis?source=see_link&sectionName=Beta-D-glucan+assay&anchor=H1064486465#H1064486465http://www.uptodate.com/contents/diagnosis-of-invasive-aspergillosis?source=see_link&sectionName=Beta-D-glucan+assay&anchor=H1064486465#H1064486465http://www.uptodate.com/contents/evaluation-and-management-of-severe-sepsis-and-septic-shock-in-adults/abstract/6http://www.uptodate.com/contents/evaluation-and-management-of-severe-sepsis-and-septic-shock-in-adults/abstract/64-66http://www.uptodate.com/contents/evaluation-and-management-of-severe-sepsis-and-septic-shock-in-adults/abstract/65http://www.uptodate.com/contents/evaluation-and-management-of-severe-sepsis-and-septic-shock-in-adults/abstract/67,68http://www.uptodate.com/contents/evaluation-and-management-of-severe-sepsis-and-septic-shock-in-adults/abstract/69-71http://www.uptodate.com/contents/evaluation-and-management-of-severe-sepsis-and-septic-shock-in-adults/abstract/69http://www.uptodate.com/contents/evaluation-and-management-of-severe-sepsis-and-septic-shock-in-adults/abstract/72http://www.uptodate.com/contents/evaluation-and-management-of-severe-sepsis-and-septic-shock-in-adults/abstract/70,71http://www.uptodate.com/contents/evaluation-and-management-of-severe-sepsis-and-septic-shock-in-adults/abstract/73,74http://www.uptodate.com/contents/evaluation-and-management-of-severe-sepsis-and-septic-shock-in-adults/abstract/72http://www.uptodate.com/contents/evaluation-and-management-of-severe-sepsis-and-septic-shock-in-adults/abstract/9


10/30

undertaken to eradicate a focus of infection and eliminate or treat ongoing microbial proliferation and

infection2 should be undertaken since undrained foci of infection may not respond to antibiotics alone

-table )2. 8s e'amples, potentially infected foreign bodies -eg, vascular access devices2 should be

removed #hen possible, and abscesses should undergo percutaneous or surgical drainage. Some

patients reuire e'tensive soft tissue debridement or amputationK in severe cases, fulminant lostridium

difficile*associated colitis may necessitate colectomy $?%.

Anti)i&robial re"i)en — +ntravenous antibiotic therapy should be initiated #ithin the first si' hours or

earlier -eg, #ithin one hour2, after obtaining appropriate cultures, since early initiation of antibiotic therapy

is associated #ith lo#er mortality $?,?6%. The choice of antibiotics can be comple' and should consider the

patient:s history -eg, recent antibiotics received $??%2, comorbidities, clinical conte't -eg, community* or

hospital*acuired2, Hram stain data, and local resistance patterns $?,?A,?4%.

0oor outcomes are associated #ith inadeuate or inappropriate antimicrobial therapy -ie, treatment #ith

antibiotics to #hich the pathogen #as later sho#n to be resistant in vitro2 $A!*A6%. They are also

associated #ith delays in initiating antimicrobial therapy, even short delays -eg, an hour2.

38 prospective cohort study of )1)( patients demonstrated that inappropriate antibiotic selection#as surprisingly common -E) percent2 $AE%. 9ortality #as markedly increased in these patients

compared to those #ho had received appropriate antibiotics -E( versus 1A percent2.

38 retrospective analysis of )?E1 patients #ith septic shock demonstrated that the time to initiation

of appropriate antimicrobial therapy #as the strongest predictor of mortality $A(%.

Bhen the potential pathogen or infection source is not immediately obvious, #e favor broad*spectrum

antibiotic coverage directed against both gram*positive and gram*negative bacteria. Je# guidelines e'ist

for the initial selection of empiric antibiotics in severe sepsis or septic shock.

Staphylococcus aureus is associated #ith significant morbidity if not treated early in the course of

infection $A?%. There is gro#ing recognition that methicillin*resistant S. aureus -95S82 is a cause of

sepsis not only in hospitalized patients, but also in community d#elling individuals #ithout recenthospitalization $AA,A4%. Jor these reasons, #e recommend that severely ill patients presenting #ith sepsis

of unclear etiology be treated #ith intravenous vancomycin -adIusted for renal function2 until the possibility

of 95S8 sepsis has been e'cluded. 0otential alternative agents to vancomycin -eg, daptomycin for non*

pulmonary 95S8,linezolid, ceftaroline2 should be considered for patients #ith refractory or virulent

95S8, or a contraindication to vancomycin. These agents are discussed separately. -See Treatment of

invasive methicillin*resistant Staphylococcus aureus infections in adults, section on

:=acteremia: and Treatment of hospital*acuired, ventilator*associated, and healthcare*associated

pneumonia in adults, section on :9ethicillin*resistant Staphylococcus aureus:.2

+n our practice, if 0seudomonas is an unlikely pathogen, #e favor combining vancomycin #ith one of the

follo#ing/

3ephalosporin, Erd generation -eg, ceftria'one or cefota'ime2 or (th generation -cefepime2, or

3=eta*lactamCbeta*lactamase inhibitor -eg, piperacillin*tazobactam, ticarcillin*clavulanate2, or

3arbapenem -eg, imipenem or meropenem2

8lternatively, if 0seudomonas is a possible pathogen, #e favor combining vancomycin #ith t#o of the

follo#ing -see 0rinciples of antimicrobial therapy of 0seudomonas aeruginosa infections2/

http://www.uptodate.com/content-not-availablehttp://www.uptodate.com/contents/evaluation-and-management-of-severe-sepsis-and-septic-shock-in-adults/abstract/75http://www.uptodate.com/contents/evaluation-and-management-of-severe-sepsis-and-septic-shock-in-adults/abstract/7,76http://www.uptodate.com/contents/evaluation-and-management-of-severe-sepsis-and-septic-shock-in-adults/abstract/77http://www.uptodate.com/contents/evaluation-and-management-of-severe-sepsis-and-septic-shock-in-adults/abstract/77http://www.uptodate.com/contents/evaluation-and-management-of-severe-sepsis-and-septic-shock-in-adults/abstract/7,78,79http://www.uptodate.com/contents/evaluation-and-management-of-severe-sepsis-and-septic-shock-in-adults/abstract/80-86http://www.uptodate.com/contents/evaluation-and-management-of-severe-sepsis-and-septic-shock-in-adults/abstract/80-86http://www.uptodate.com/contents/evaluation-and-management-of-severe-sepsis-and-septic-shock-in-adults/abstract/83http://www.uptodate.com/contents/evaluation-and-management-of-severe-sepsis-and-septic-shock-in-adults/abstract/84http://www.uptodate.com/contents/evaluation-and-management-of-severe-sepsis-and-septic-shock-in-adults/abstract/87http://www.uptodate.com/contents/evaluation-and-management-of-severe-sepsis-and-septic-shock-in-adults/abstract/88,89http://www.uptodate.com/contents/vancomycin-drug-information?source=see_linkhttp://www.uptodate.com/contents/daptomycin-drug-information?source=see_linkhttp://www.uptodate.com/contents/daptomycin-drug-information?source=see_linkhttp://www.uptodate.com/contents/linezolid-drug-information?source=see_linkhttp://www.uptodate.com/contents/linezolid-drug-information?source=see_linkhttp://www.uptodate.com/contents/ceftaroline-drug-information?source=see_linkhttp://www.uptodate.com/contents/treatment-of-invasive-methicillin-resistant-staphylococcus-aureus-infections-in-adults?source=see_link&sectionName=Bacteremia&anchor=H14#H14http://www.uptodate.com/contents/treatment-of-invasive-methicillin-resistant-staphylococcus-aureus-infections-in-adults?source=see_link&sectionName=Bacteremia&anchor=H14#H14http://www.uptodate.com/contents/treatment-of-invasive-methicillin-resistant-staphylococcus-aureus-infections-in-adults?source=see_link&sectionName=Bacteremia&anchor=H14#H14http://www.uptodate.com/contents/treatment-of-invasive-methicillin-resistant-staphylococcus-aureus-infections-in-adults?source=see_link&sectionName=Bacteremia&anchor=H14#H14http://www.uptodate.com/contents/treatment-of-invasive-methicillin-resistant-staphylococcus-aureus-infections-in-adults?source=see_link&sectionName=Bacteremia&anchor=H14#H14http://www.uptodate.com/contents/treatment-of-hospital-acquired-ventilator-associated-and-healthcare-associated-pneumonia-in-adults?source=see_link&sectionName=Methicillin-resistant+Staphylococcus+aureus&anchor=H7#H7http://www.uptodate.com/contents/treatment-of-hospital-acquired-ventilator-associated-and-healthcare-associated-pneumonia-in-adults?source=see_link&sectionName=Methicillin-resistant+Staphylococcus+aureus&anchor=H7#H7http://www.uptodate.com/contents/vancomycin-drug-information?source=see_linkhttp://www.uptodate.com/contents/ceftriaxone-drug-information?source=see_linkhttp://www.uptodate.com/contents/ceftriaxone-drug-information?source=see_linkhttp://www.uptodate.com/contents/ceftriaxone-drug-information?source=see_linkhttp://www.uptodate.com/contents/cefotaxime-drug-information?source=see_linkhttp://www.uptodate.com/contents/cefepime-drug-information?source=see_linkhttp://www.uptodate.com/contents/piperacillin-and-tazobactam-sodium-drug-information?source=see_linkhttp://www.uptodate.com/contents/piperacillin-and-tazobactam-sodium-drug-information?source=see_linkhttp://www.uptodate.com/contents/ticarcillin-and-clavulanate-potassium-drug-information?source=see_linkhttp://www.uptodate.com/contents/imipenem-and-cilastatin-drug-information?source=see_linkhttp://www.uptodate.com/contents/meropenem-drug-information?source=see_linkhttp://www.uptodate.com/contents/meropenem-drug-information?source=see_linkhttp://www.uptodate.com/contents/vancomycin-drug-information?source=see_linkhttp://www.uptodate.com/contents/vancomycin-drug-information?source=see_linkhttp://www.uptodate.com/contents/vancomycin-drug-information?source=see_linkhttp://www.uptodate.com/contents/principles-of-antimicrobial-therapy-of-pseudomonas-aeruginosa-infections?source=see_linkhttp://www.uptodate.com/content-not-availablehttp://www.uptodate.com/contents/evaluation-and-management-of-severe-sepsis-and-septic-shock-in-adults/abstract/75http://www.uptodate.com/contents/evaluation-and-management-of-severe-sepsis-and-septic-shock-in-adults/abstract/7,76http://www.uptodate.com/contents/evaluation-and-management-of-severe-sepsis-and-septic-shock-in-adults/abstract/77http://www.uptodate.com/contents/evaluation-and-management-of-severe-sepsis-and-septic-shock-in-adults/abstract/7,78,79http://www.uptodate.com/contents/evaluation-and-management-of-severe-sepsis-and-septic-shock-in-adults/abstract/80-86http://www.uptodate.com/contents/evaluation-and-management-of-severe-sepsis-and-septic-shock-in-adults/abstract/83http://www.uptodate.com/contents/evaluation-and-management-of-severe-sepsis-and-septic-shock-in-adults/abstract/84http://www.uptodate.com/contents/evaluation-and-management-of-severe-sepsis-and-septic-shock-in-adults/abstract/87http://www.uptodate.com/contents/evaluation-and-management-of-severe-sepsis-and-septic-shock-in-adults/abstract/88,89http://www.uptodate.com/contents/vancomycin-drug-information?source=see_linkhttp://www.uptodate.com/contents/daptomycin-drug-information?source=see_linkhttp://www.uptodate.com/contents/linezolid-drug-information?source=see_linkhttp://www.uptodate.com/contents/ceftaroline-drug-information?source=see_linkhttp://www.uptodate.com/contents/treatment-of-invasive-methicillin-resistant-staphylococcus-aureus-infections-in-adults?source=see_link&sectionName=Bacteremia&anchor=H14#H14http://www.uptodate.com/contents/treatment-of-invasive-methicillin-resistant-staphylococcus-aureus-infections-in-adults?source=see_link&sectionName=Bacteremia&anchor=H14#H14http://www.uptodate.com/contents/treatment-of-invasive-methicillin-resistant-staphylococcus-aureus-infections-in-adults?source=see_link&sectionName=Bacteremia&anchor=H14#H14http://www.uptodate.com/contents/treatment-of-hospital-acquired-ventilator-associated-and-healthcare-associated-pneumonia-in-adults?source=see_link&sectionName=Methicillin-resistant+Staphylococcus+aureus&anchor=H7#H7http://www.uptodate.com/contents/treatment-of-hospital-acquired-ventilator-associated-and-healthcare-associated-pneumonia-in-adults?source=see_link&sectionName=Methicillin-resistant+Staphylococcus+aureus&anchor=H7#H7http://www.uptodate.com/contents/vancomycin-drug-information?source=see_linkhttp://www.uptodate.com/contents/ceftriaxone-drug-information?source=see_linkhttp://www.uptodate.com/contents/cefotaxime-drug-information?source=see_linkhttp://www.uptodate.com/contents/cefepime-drug-information?source=see_linkhttp://www.uptodate.com/contents/piperacillin-and-tazobactam-sodium-drug-information?source=see_linkhttp://www.uptodate.com/contents/ticarcillin-and-clavulanate-potassium-drug-information?source=see_linkhttp://www.uptodate.com/contents/imipenem-and-cilastatin-drug-information?source=see_linkhttp://www.uptodate.com/contents/meropenem-drug-information?source=see_linkhttp://www.uptodate.com/contents/vancomycin-drug-information?source=see_linkhttp://www.uptodate.com/contents/principles-of-antimicrobial-therapy-of-pseudomonas-aeruginosa-infections?source=see_link


11/30

38ntipseudomonal cephalosporin -eg, ceftazidime, cefepime2, or

38ntipseudomonal carbapenem -eg, imipenem, meropenem2, or

38ntipseudomonal beta*lactamCbeta*lactamase inhibitor -eg, piperacillin*tazobactam, ticarcillin*

clavulanate2, or

3Jluorouinolone #ith good anti*pseudomonal activity -eg, ciproflo'acin2, or

38minoglycoside -eg, gentamicin, amikacin2, or

39onobactam -eg, aztreonam2

Selection of t#o agents from the same class, for e'ample, t#o beta*lactams, should be avoided. Be

emphasize the importance of considering local susceptibility patterns #hen choosing an empiric antibiotic

regimen.

8fter culture results and antimicrobial susceptibility data return, #e recommend that therapy be pathogen*

and susceptibility*directed, even if there has been clinical improvement #hile on the initial antimicrobial

regimen. Hram*negative pathogens have historically been covered #ith t#o agents from different

antibiotic classes. ;o#ever, several clinical trials and t#o meta*analyses have failed to demonstrate

superior overall efficacy of combination therapy compared to monotherapy #ith a third generationcephalosporin or a carbapenem $AE,4!*4(%. Jurthermore, one meta*analysis found double coverage that

included an aminoglycoside #as associated #ith an increased incidence of adverse events

-nephroto'icity2 $4E,4(%. Jor this reason, in patients #ith gram negative pathogens, #e recommend use of

a single agent #ith proven efficacy and the least possible to'icity, e'cept in patients #ho are either

neutropenic or #hose severe sepsis is due to a kno#n or suspected 0seudomonas infection $?,4)%.

-See 0seudomonas aeruginosa bacteremia and endocarditis and 0rinciples of antimicrobial therapy of

0seudomonas aeruginosa infections.2

5egardless of the antibiotic regimen selected, patients should be observed closely for to'icity, evidence of

response, and the development of nosocomial superinfection $4%. There are no published randomized

controlled trials testing safety of de*escalation of antibiotic therapy in adult patients #ith sepsis or septic

shock $46%. The duration of therapy is typically ? to 1! days, although longer courses may be appropriate

in patients #ho have a slo# clinical response, an undrainable focus of infection, or immunologic

deficiencies $?%. +n patients #ho are neutropenic, antibiotic treatment s