Sepsis 2018:
Sepsis 2018:
Definitions and Guideline Changes
Definitions and Guideline Changes
Lena M.
Lena M. NapoliNapolitanotano
Abstract Abstract
Background:
Background: Sepsis is a global healthcare issue and continues to be the leading cause of death from infection.
Sepsis is a global healthcare issue and continues to be the leading cause of death from infection.
Early recognit
Early recognition and
ion and diagnosi
diagnosis of
s of sepsis is required to
sepsis is required to prevent the transition into septic shock, which
prevent the transition into septic shock, which is associated
is associated
with a mortality rate of 40% or more.
with a mortality rate of 40% or more.
Discussion:
Discussion: New definitions for sepsis and septic shock (Third International Consensus Definitions for Sepsis and
New definitions for sepsis and septic shock (Third International Consensus Definitions for Sepsis and
Septic Shock [Sepsis-3]) have been developed. A new screening tool for sepsis (quick Sequential Organ Failure
Septic Shock [Sepsis-3]) have been developed. A new screening tool for sepsis (quick Sequential Organ Failure
Ass
Assessm
essment
ent [qS
[qSOFA
OFA])
]) has
has been
been prop
proposed to
osed to pre
predic
dict
t the
the like
likelih
lihood
ood of
of poor outcome in
poor outcome in out-
out-of-
of-int
intensi
ensive
ve car
caree
unit (ICU) patients with clinical suspicion of sepsis. The Surviving Sepsis Campaign Guidelines were recently
unit (ICU) patients with clinical suspicion of sepsis. The Surviving Sepsis Campaign Guidelines were recently
updated and include greater evidence-based recommendations for treatment of sepsis in attempts to reduce
updated and include greater evidence-based recommendations for treatment of sepsis in attempts to reduce
sepsis-associated mortality. This review discusses the new Sepsis-3 definitions and guidelines.
associated mortality. This review discusses the new Sepsis-3 definitions and guidelines.
Keywords:
Keywords: sepsis; sepsis guidelines; Sepsis-3 definition; septic shock; Surviving Sepsis Campaign
sepsis; sepsis guidelines; Sepsis-3 definition; septic shock; Surviving Sepsis Campaign
S
S
epsis continues to beepsis continues to be a major health problem world- a major health problem world-wide and is associated with high mortality rates. The wide and is associated with high mortality rates. The Intensive Care Over Nations (ICON) study provided global Intensive Care Over Nations (ICON) study provided global epidemiologic data on 10,069 intensive care unit (ICU) epidemiologic data on 10,069 intensive care unit (ICU) pa-tients and confirmed thatients and confirmed that 2,973 (29.5%) oft 2,973 (29.5%) of patients had sepsispatients had sepsis on admission or during their ICU stay. In patients with on admission or during their ICU stay. In patients with sep-sis, ICU mortality was 25.8%, and hospital mortality was sis, ICU mortality was 25.8%, and hospital mortality was 35.3
35.3%, whi%, whichch was awas a signsignificanificantlytly highigher morher mortalitalityty rate trate thanhan inin the general ICU population (ICU mortality, 16.2%; hospital the general ICU population (ICU mortality, 16.2%; hospital mort
mortalitality, y, 24.224.2%) %) [1]. [1]. OptiOptimal mal evidevidenceence-base-based d treattreatmentment of sepsis is therefore needed in attempts to reduce mortality, of sepsis is therefore needed in attempts to reduce mortality, led over the last decade by the Surviving Sepsis Campaign led over the last decade by the Surviving Sepsis Campaign (SSC). The first step in implementation of optimal sepsis (SSC). The first step in implementation of optimal sepsis treatment is identification of patients with sepsis. This treatment is identification of patients with sepsis. This articlearticle discusses the new Third International Consensus Definitions discusses the new Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3) definitions for sepsis for Sepsis and Septic Shock (Sepsis-3) definitions for sepsis and septic shock and the new 2016 SSC guidelines.
and septic shock and the new 2016 SSC guidelines.
Sepsis-3: New Definitions Sepsis-3: New Definitions
Initial sepsis definitions were developed at a 1991 Initial sepsis definitions were developed at a 1991 con-sensus conference [2] with a subsequent update in the sepsis sensus conference [2] with a subsequent update in the sepsis definitions in 2001 that simply expanded the list of signs and definitions in 2001 that simply expanded the list of signs and symptoms of sepsis to reflect clinical bedside experience [3]. symptoms of sepsis to reflect clinical bedside experience [3]. The initial sepsis definitions included sepsis (systemic The initial sepsis definitions included sepsis (systemic in-flammatory response syndrome [SIRS] and suspected flammatory response syndrome [SIRS] and suspected
infec-tion), severe sepsis (sepsis and organ dysfunction) and septic tion), severe sepsis (sepsis and organ dysfunction) and septic shock (sepsis and hypotension despite adequate fluid shock (sepsis and hypotension despite adequate fluid resus-citation; Fig. 1).
citation; Fig. 1).
An international task force with 19 participants was An international task force with 19 participants was con-vened by the Society of Critical Care Medicine (SCCM) and vened by the Society of Critical Care Medicine (SCCM) and the
the EurEuropopeanean SocSocietietyy ofof IntIntensensiveive CarCaree MedMediciicinene (ES(ESICMICM)) toto revise the current sepsis and septic shock definitions. Using revise the current sepsis and septic shock definitions. Using an expert Delphi consensus process,
an expert Delphi consensus process, this group developed thethis group developed the new Sepsis-3 definitions [4,5]. They moved away from the new Sepsis-3 definitions [4,5]. They moved away from the assoc
associatiiation on betwbetween een infeinfectioction n and and inflainflammatmmation ion and and com- com-pletely abandoned SIRS criteria.
pletely abandoned SIRS criteria. Seps
Sepsis is is is defindefined ed as as lifelife-thre-threatenatening ing organ dysfunctorgan dysfunctionion caus
caused ed by by a a dysrdysregulegulated host ated host respresponse to onse to infecinfectiontion. . TheThe clinical criteria for sepsis include suspected or documented clinical criteria for sepsis include suspected or documented infection and an acute increase of two or more Sequential infection and an acute increase of two or more Sequential Organ Failure Assessment (SOFA) points as a proxy for Organ Failure Assessment (SOFA) points as a proxy for or-gan dysfunction. Septic shock is defined as a subset of sepsis gan dysfunction. Septic shock is defined as a subset of sepsis in which underlying circulatory and cellular/metabolic in which underlying circulatory and cellular/metabolic ab-normalities are profound enough to increase mortality normalities are profound enough to increase mortality sub-stantially. Septic shock is defined by the clinical criteria of stantially. Septic shock is defined by the clinical criteria of sepsis and vasopressor therapy needed to elevate mean sepsis and vasopressor therapy needed to elevate mean ar-teria
teriall presspressureure‡‡65mm65mm HgHg anandd lalactctatatee>>22 mmommol/Ll/L (18mg/dL(18mg/dL))
despite adequate fluid resuscitation (Fig. 1). despite adequate fluid resuscitation (Fig. 1).
The mortality rate associated with the new septic shock The mortality rate associated with the new septic shock defi
definitnition ion is is hihigh gh (40(40%) %) comcomparpared ed wiwith th a a mormortatalitlity y ratratee of 10% with the new sepsis definition. A systematic review of 10% with the new sepsis definition. A systematic review
Acute Care Surgery, Trauma and Surgical Critical Care, University of Michigan Health System, Ann Arbor, Michigan. Acute Care Surgery, Trauma and Surgical Critical Care, University of Michigan Health System, Ann Arbor, Michigan.
ª
ª Mary Ann Liebert, Inc. Mary Ann Liebert, Inc.
DOI:
DOI: 10.1089/s10.1089/sur.2017.278ur.2017.278
117 117 D D o o w w n n l l o o a a d d e e d d b b y y G G u u a a n n g g x x i i U U n n i i v v e e
r r s s i i t t y y f f o o r r N N a a t t i i o o n n
a a l l i i t t i i e e s s f f r r o o m m o o n n l l i i n n e e
. . l l i i e e b b e e r r t t p p u u b b c c . . o o m m a a t t 0 0 2 2 / / 1 1 6 6 / / 1 1 8 8 . . F F o o r r p p e e r r s s o o n n a a l l u u s s e e o o n n l l y y . .
identified 44 studies reporting septic shock outcomes, and identified 44 studies reporting septic shock outcomes, and the
the DelpDelphi hi procprocess ess idenidentifietified d hypohypotenstension, ion, lactlactate ate concconcen- en-tration, and vasopressor therapy as clinical criteria to tration, and vasopressor therapy as clinical criteria to iden-tify patients with septic shock. Based on these parameters, tify patients with septic shock. Based on these parameters, specific patient groups with or without these clinical criteria specific patient groups with or without these clinical criteria were developed, and their prevalence and associated were developed, and their prevalence and associated
mor-tality rates were examined in the SSC database (Table 1). tality rates were examined in the SSC database (Table 1). The group requiring vasopressors to maintain mean arterial The group requiring vasopressors to maintain mean arterial pres
pressure 65sure 65 mm Hg mm Hg or greater and or greater and a a lactlactate concenate concentrattrationion
>
>22 mmol/L (18mmol/L (18 mg/dL) after fluimg/dL) after fluid resuscitatid resuscitation (group 1) hadon (group 1) had
a higher mortality (42.3%) in
a higher mortality (42.3%) in risk-adjusted comparisorisk-adjusted comparisons withns with the other five groups. This analysis led to the new Sepsis-3 the other five groups. This analysis led to the new Sepsis-3 septic shock definition [6]. It should also be noted, septic shock definition [6]. It should also be noted, how-ever, that patients who met the Sepsis-2 criteria for septic ever, that patients who met the Sepsis-2 criteria for septic shock (group 2) with hypotension, requiring vasopressors, shock (group 2) with hypotension, requiring vasopressors, but without lactate elevation, also had a high mortality rate of but without lactate elevation, also had a high mortality rate of 30.1%. The higher mortality rate associated with this new 30.1%. The higher mortality rate associated with this new definition of septic shock has important implications for trial definition of septic shock has important implications for trial design in septic shock and may allow decreased sample size design in septic shock and may allow decreased sample size for future septic shock trials [7].
for future septic shock trials [7].
Controversy remains regarding the inclusion of lactate in Controversy remains regarding the inclusion of lactate in the Sepsis-3 septic shock
the Sepsis-3 septic shock defindefinitioition n and the and the exacexact t lactlactateate measurement (
measurement (>> 2 2 mmol/L) used in the definitmmol/L) used in the definition. One studyion. One study
analyzed a prospective cohort of ICU patients with sepsis analyzed a prospective cohort of ICU patients with sepsis (n
(n==632) and documented that patients meeting the Sepsis-3632) and documented that patients meeting the Sepsis-3
definition of septic shock had a
definition of septic shock had a higher mortality than patientshigher mortality than patients meeting the Sepsis-2 definition (38.9% vs. 34.0%), but only meeting the Sepsis-2 definition (38.9% vs. 34.0%), but only lact
lactateate valuvalueses‡‡66 mmommol/Ll/L wewerere assassociociateatedd wiwithth incincreareasedsed ICUICU
mortality [8]. Others report concern that lactate is a sensitive mortality [8]. Others report concern that lactate is a sensitive but not specific indicator of cellular or metabolic stress rather but not specific indicator of cellular or metabolic stress rather than ‘‘shock.’’
than ‘‘shock.’’
SIRS versus SOFA and qSOFA in Sepsis SIRS versus SOFA and qSOFA in Sepsis
A retrospective analysis of the Australian and New A retrospective analysis of the Australian and New Zeal-and Intensive Care
and Intensive Care Society (ANZICS) database (2000–2013)Society (ANZICS) database (2000–2013) included 109,663 patients with infection and organ failure included 109,663 patients with infection and organ failure to validate the severe sepsis definition [9]. It was reported to validate the severe sepsis definition [9]. It was reported that 87.9% of patients had two or more SIRS criteria but that 87.9% of patients had two or more SIRS criteria but 12.1% did not. Using SIRS alone missed
12.1% did not. Using SIRS alone missed one in eight patientsone in eight patients with severe sepsis. The study confirmed that each additional with severe sepsis. The study confirmed that each additional SIRS criteria increased mortality by 13% in a linear manner SIRS criteria increased mortality by 13% in a linear manner without a transitional increase when two SIRS criteria were without a transitional increase when two SIRS criteria were me
met.t. ThTheyey coconcncluludededd ththatat ththee ususee ofof twtwoo oror momorere SISIRSRS crcrititereriaia alone lacked both sensitivity and specificity for diagnosing alone lacked both sensitivity and specificity for diagnosing severe sepsis in ICU patients.
severe sepsis in ICU patients.
The subsequent analysis of clinical criteria for the new The subsequent analysis of clinical criteria for the new Sepsis-3 definitio
Sepsis-3 definitions compared SIRS ns compared SIRS criteriacriteria, , the SOFA the SOFA score,score, the Logistic Organ Dysfunction System (LODS) score, and the Logistic Organ Dysfunction System (LODS) score, and the quick SOFA (qSOFA) score (range, 0–3 points, with one the quick SOFA (qSOFA) score (range, 0–3 points, with one poi
pointnt eacheach forfor systsystoliolicc hyphypoteotensinsionon [[££100100 mmmm Hg],Hg], tactachyphypneanea
[[‡‡ 22/min], or altered mentation). The SOFA score (Table 2) 22/min], or altered mentation). The SOFA score (Table 2)
FI
FIG. G. 1.1. Third Third InteInternatrnationaional l ConsConsensuensus s DefinDefinitioitions ns forfor Sepsis and Septic Shock (Sepsis-3): (
Sepsis and Septic Shock (Sepsis-3): ( aa) ) OrigOriginal Sepsis-2inal Sepsis-2 definitions; (
definitions; (bb) New Sepsis-3 definitions.) New Sepsis-3 definitions.
Table
Table 1. 1. Distribution and Mortality in Septic Shock Cohorts from Surviving Sepsis Campaign Database Distribution and Mortality in Septic Shock Cohorts from Surviving Sepsis Campaign Database
Hypotension Hypotension
af
afteter r flufluidids s VaVasosoprpresessosors rs LaLactctatatee>>22 mmolmmol/L /L
Prevalence, Surviving Sepsis Prevalence, Surviving Sepsis Campaign Database (n
Campaign Database (n==18,840 18,840 patientspatients))
Hospital Hospital mortality mortality Group 1
Group 1aa YYees s YYees s YYees s 8,,585220 0 ((4455..22%%) ) 4422..33%% Group 2
Group 2bb YYees s YYees s NNo o 33,,99885 5 ((2211..22%%) ) 3300..11%% G
Grroouup p 3 3 YYees s NNo o YYees s 22223 3 ((11..22%%) ) 2288..77%% G
Grroouup p 4 4 NNo o NNo o YYees s 33,,22666 6 ((1177..33%%) ) 2255..77%% G
Grroouup p 5 5 NNeevveer r ((pprree) ) NNo o YYees s 22,,66996 6 ((1144..33%%) ) 2299..77%% G
Grroouup p 6 6 YYees s NNo o NNo o 11550 0 ((00..88%%) ) 1188..77%%
a a
Meets criteria for new Sepsis-3 septic shock definition. Meets criteria for new Sepsis-3 septic shock definition.
b b
Meets criteria for old Sepsis-2 septic shock definition. Meets criteria for old Sepsis-2 septic shock definition.
Data compiled from: Shankar-Hari M, Phillips GS, Levey ML, et al. Developing a new definition and assessing new clinical criteria for Data compiled from: Shankar-Hari M, Phillips GS, Levey ML, et al. Developing a new definition and assessing new clinical criteria for septic shock. For the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA 2016;315:775–787. septic shock. For the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA 2016;315:775–787.
Sepsis-3
Sepsis-3==Third International Consensus Definitions for Sepsis and Septic Shock.Third International Consensus Definitions for Sepsis and Septic Shock.
D D o o w w n n l l o o a a d d e e d d b b y y G G u u a a n n g g x x i i U U n n i i v v e e
r r s s i i t t y y f f o o r r N N a a t t i i o o n n
a a l l i i t t i i e e s s f f r r o o m m o o n n l l i i n n e e
. . l l i i e e b b e e r r t t p p u u b b c c . . o o m m a a t t 0 0 2 2 / / 1 1 6 6 / / 1 1 8 8 . . F F o o r r p p e e r r s s o o n n a a l l u u s s e e o o n n l l y y . .
is widely used in critical care research, but is not a common is widely used in critical care research, but is not a common clinical tool used at the bedside in the ICU [10].
clinical tool used at the bedside in the ICU [10]. The qSOFA score (Fig
The qSOFA score (Fig. . 2) 2) wawas s dedevelvelopoped ed as as a a simsimplplee screening tool to identify patients with possible sepsis. A screening tool to identify patients with possible sepsis. A qS
qSOFOFAA scscororee ofof twtwoo oror momorere ididenentitifiefiess aa papatitienentt atat grgreaeateterr ririsk sk of
of poopoor r outcoutcome. Among ome. Among non-non-ICU ICU encoencounteunters rs in in patipatientsents with suspect
with suspected infection, qSOed infection, qSOFAFA had ahad a predictive vpredictive validity foralidity for in-h
in-hospiospital tal mortmortalitality y (area (area undeunder r the the receireceiver ver operoperatinatingg characteristi
characteristic curve c curve [AUROC] 0.81) that was [AUROC] 0.81) that was greater than thegreater than the full SOFA score (AUROC 0.79) and SIRS (AUROC 0.76; full SOFA score (AUROC 0.79) and SIRS (AUROC 0.76; Table 3). In contrast, however, in the ICU, the predictive Table 3). In contrast, however, in the ICU, the predictive
val
validiidity ty for for in-in-hoshospipital tal mormortaltalitity y was was lowlower er for for qSOqSOFAFA (AUROC 0.66) and SIRS (AUROC 0.64) compared with the (AUROC 0.66) and SIRS (AUROC 0.64) compared with the full SOFA score (AUROC 0.74) [5].
full SOFA score (AUROC 0.74) [5].
The use of the SOFA score in the Sepsis-3 definition is The use of the SOFA score in the Sepsis-3 definition is challengi
challenging, because SOFA is ng, because SOFA is a complicated score that is nota complicated score that is not calc
calculatulated ed routiroutinely in nely in ICUs at ICUs at the bedsidethe bedside. . SysteSystemic mic in- in-flammatory response syndrome and qSOFA are scores that flammatory response syndrome and qSOFA are scores that are easily calculated at the bedside for use
are easily calculated at the bedside for use in the screening of in the screening of patients with possible sepsis. A retrospective cohort analysis patients with possible sepsis. A retrospective cohort analysis of the ANZICS database that was used to assess SIRS in the of the ANZICS database that was used to assess SIRS in the se
sevevere re sesepspsis is dedefinfinititioion n wawas s alalso so usused ed to to cocompmparare e ththee
Table
Table 2. 2. Sequential (Sepsis-Related) Organ Failure Assessment (Sofa) Score Sequential (Sepsis-Related) Organ Failure Assessment (Sofa) Scoreaa
System System Score Score 0 0 11 22 33 44 Respiration Respiration Pao
Pao22 /Fio /Fio22, mm Hg, mm Hg
(kPa) (kPa) ‡ ‡400 (53.3)400 (53.3) <<400 (53.3)400 (53.3) <<300 (40)300 (40) <<200 (26.7) with200 (26.7) with respiratory support respiratory support < <100 (13.3) with100 (13.3) with respiratory support respiratory support Coagulation Coagulation Platelets, Platelets,··101033 / / mmLL ‡‡150150 <<150150 <<100100 <<5050 <<2020 Liver Liver Bilirubin, mg/dL Bilirubin, mg/dL ((mmmol/L)mol/L) < <1.1.2 2 (2(20) 0) 1.1.2–2–1.1.9 9 (2(20–0–3232) ) 2.2.0–0–5.5.9 9 (3(33–3–10101) 1) 6.6.0–0–1111.9 .9 (1(10202–2–20404)) >>12.0 (204)12.0 (204) C
Caarrddiioovvaassccuullaar r MMAAPP ‡‡70mm Hg 70mm Hg MAMAPP <<70mm 70mm Hg Hg DoDopapamiminene <<55
or dobutamine or dobutamine (any dose) (any dose)bb Dopamine 5.1–15 or Dopamine 5.1–15 or epinephrine epinephrine ££0.1 or0.1 or norepinephrine norepinephrine ££0.10.1bb Dopamine Dopamine >>15 or15 or epinephrine epinephrine >>0.1 or0.1 or norepinephrine norepinephrine >>0.10.1bb Central nervous Central nervous system system Glasgow coma Glasgow coma scale score scale scorecc 1 15 5 1133––114 4 1100––112 2 66––99 <<66 Renal Renal Creatinine, mg/dL Creatinine, mg/dL ((mmmol/L)mol/L) < <1.2 1.2 (11(110) 0) 1.21.2–1–1.9 .9 (11(110–10–170) 70) 2.02.0–3–3.4 .4 (17(171–1–299299) ) 3.53.5–4.–4.9 (9 (30300–40–440)40) >>5.0 (440)5.0 (440) Urine output, mL/d Urine output, mL/d <<500500 <<200200 Fio
Fio22==fraction of inspired oxygen; MAPfraction of inspired oxygen; MAP==mean arterial pressure; Paomean arterial pressure; Pao22==partiapartial l presspressure ure of of oxygen.oxygen. a
a
Adapted from Vincent et al. [10]. Adapted from Vincent et al. [10].
b b
Catecholamine doses are given as
Catecholamine doses are given as mmg/kg/min for at least 1 hour.g/kg/min for at least 1 hour. c
c
Glasgow coma scale scores range from 3–15; higher score indicates better neurological function. Glasgow coma scale scores range from 3–15; higher score indicates better neurological function.
FIG. 2.
FIG. 2. Quick SequenQuick Sequential Organ Failure Assessmtial Organ Failure Assessment (qSOFA) score for sepsis.ent (qSOFA) score for sepsis.
D D o o w w n n l l o o a a d d e e d d b b y y G G u u a a n n g g x x i i U U n n i i v v e e
r r s s i i t t y y f f o o r r N N a a t t i i o o n n
a a l l i i t t i i e e s s f f r r o o m m o o n n l l i i n n e e
. . l l i i e e b b e e r r t t p p u u b b c c . . o o m m a a t t 0 0 2 2 / / 1 1 6 6 / / 1 1 8 8 . . F F o o r r p p e e r r s s o o n n a a l l u u s s e e o o n n l l y y . .
prognostic accuracy of the SOFA score, SIRS criteria, and prognostic accuracy of the SOFA score, SIRS criteria, and qSOFA score for in-hospital mortality among adults with qSOFA score for in-hospital mortality among adults with sus-pec
pectedtedinfeinfectictionon admadmittitteded toto thethe ICU.ICU.TheThe SOFAscoreSOFAscore incincreasreaseded bytwoor
bytwoor momorepoirepointntss in90.in90.1%1%;; 8686.7.7%% hahadd SISIRSscoRSscorere ofof twtwoo oror more, and 54.4% had a qSOFA score of two or more. An more, and 54.4% had a qSOFA score of two or more. An in-crease in SOFA score of two or more had greater prognostic crease in SOFA score of two or more had greater prognostic accuracy for in-hospital mortality (AUROC 0.753) than SIRS accuracy for in-hospital mortality (AUROC 0.753) than SIRS (AUROC 0.589) or the qSOFA score (AUROC 0.607) [11]. (AUROC 0.589) or the qSOFA score (AUROC 0.607) [11].
Interestingly
Interestingly, qSOFA f, qSOFA failed validatioailed validation in n in a study of a study of 30,67730,677 pati
patientsentswithwithsuspesuspectedctedinfecinfectiontionfromfrom thetheemergeemergencyncydepardepartmenttment and ward at the University of Chicago. Systemic inflammatory and ward at the University of Chicago. Systemic inflammatory respo
response nse syndrsyndrome, ome, qSOFAqSOFA, , ModiModified fied Early Warning ScoreEarly Warning Score (MEWS), and National Early Warning Score (NEWS; Table 4) (MEWS), and National Early Warning Score (NEWS; Table 4) wer
weree comcomparpared.ed.UsiUsingng thehighethehighestst nonnon-ICUscore-ICUscore ofof patpatienients,ts,twotwo or
or momorere SIRSIRSS hahadd aa sesensnsititivivitityy ofof 9191%% anandd spspececifiificicityty ofof 1313%% forfor the composite outcome (death or ICU transfer) compared with the composite outcome (death or ICU transfer) compared with 54% and 67% for qSOFA of two or more, 59% and 70% for 54% and 67% for qSOFA of two or more, 59% and 70% for MEWS of five or more, and 67% and 66% for NEWS of eight MEWS of five or more, and 67% and 66% for NEWS of eight or more, respectively. The authors concluded that the qSOFA or more, respectively. The authors concluded that the qSOFA score should not replace general early warning scores when score should not replace general early warning scores when risk-stratifying patients with suspected infection [12].
risk-stratifying patients with suspected infection [12].
In contrast, an international prospective cohort study from In contrast, an international prospective cohort study from Europe included 879 patients in the emergency department Europe included 879 patients in the emergency department
with suspected infection and examined qSOFA as
with suspected infection and examined qSOFA as a mortalitya mortality predictor. The overall in-hospital mortality was low (8%). predictor. The overall in-hospital mortality was low (8%). The qSOFA performed better than SIRS and SOFA in The qSOFA performed better than SIRS and SOFA in pre-diction of in-hospital mortality (AURO
diction of in-hospital mortality (AUROC 0.8 qSOFA C 0.8 qSOFA vs. 0.77vs. 0.77 SOFA and 0.65 SIRS). Both qSOFA and SOFA had lower SOFA and 0.65 SIRS). Both qSOFA and SOFA had lower sensitivity (qSOFA 70%, SOFA 73% vs. SIRS 93%), and sensitivity (qSOFA 70%, SOFA 73% vs. SIRS 93%), and SIRS had lower specificity (qSOFA 79%, SOFA 70%, SIRS SIRS had lower specificity (qSOFA 79%, SOFA 70%, SIRS 27%) [13]. The use of qSOFA versus SIRS score for a sepsis 27%) [13]. The use of qSOFA versus SIRS score for a sepsis scre
screen en actuactually dependally depends s on on whetwhether her you desire you desire incrincreaseeasedd sensitivity or specificity.
sensitivity or specificity.
There is still controversy regarding the new Sepsis-3 There is still controversy regarding the new Sepsis-3 def-init
initions ions [14–[14–16]. 16]. Some Some orgaorganizanizationtions s have have not not endoendorsedrsed the new Sepsis-3
the new Sepsis-3 definitiondefinitions, including the s, including the American CollegeAmerican College of Chest Physicians [17], the Infectious Disease Society of of Chest Physicians [17], the Infectious Disease Society of America, the Latin American Sepsis
America, the Latin American Sepsis Institute [18], AmericanInstitute [18], American College of Emergency Physicians, none of the emergency College of Emergency Physicians, none of the emergency medicine societies, and none of the hospital medicine medicine societies, and none of the hospital medicine soci-eties. Additional prospective validation of the new Sepsis-3 eties. Additional prospective validation of the new Sepsis-3 definitions is clearly warranted.
definitions is clearly warranted.
SSC Guidelines SSC Guidelines
The SSC guidelines for the management of severe sepsis The SSC guidelines for the management of severe sepsis and septic shock were first published in 2004 [19] with an and septic shock were first published in 2004 [19] with an up
updadatete inin 20200808 [2[20]0] anandd 20201212 [2[21]1].. ThThee ovoveraerallll gogoalal ofof ththee SSSSCC was to reduce mortality from severe sepsis and septic shock. was to reduce mortality from severe sepsis and septic shock. Active participation in the SSC was associated with increased Active participation in the SSC was associated with increased guideline adherence and reductions in sepsis-related mortality guideline adherence and reductions in sepsis-related mortality [22]. Adherence to the SSC guidelines was promoted via the [22]. Adherence to the SSC guidelines was promoted via the use of SSC bundles, which included elements to be completed use of SSC bundles, which included elements to be completed in a specific timeframe after the diagnosis of sepsis.
in a specific timeframe after the diagnosis of sepsis.
SSC bundles SSC bundles
The SSC bundles have changed during the SSC The SSC bundles have changed during the SSC guide-line update
line updates s (Table 5). The (Table 5). The differendifferences between the 2008ces between the 2008 and 2012 bundles included an increase in fluid and 2012 bundles included an increase in fluid resuscita-tion recommended for sepsis-induced tissue hypoperfusion tion recommended for sepsis-induced tissue hypoperfusion
Table
Table 3. 3. In-Hospital Mortality Prediction In-Hospital Mortality Prediction among Patients with Possible Infection Outside among Patients with Possible Infection Outside
of the Intensive Care Unit of the Intensive Care Unit
Test Test AUROC AUROC curve curve Sensitivity Sensitivity for
for mortalitymortality
Specificity Specificity for
for mortalitymortality SIRS SIRS ‡‡2 2 00..776 6 6644% % 6655%% SOFA SOFA ‡‡2 2 00..779 9 6688% % 6677%% qSOFA qSOFA ‡‡2 2 00..881 1 5555% % 8844%% AUROC
AUROC==area under the receiver operating curve; SIRSarea under the receiver operating curve; SIRS==sys-
sys-temic inflammatory response syndrome; SOFA
temic inflammatory response syndrome; SOFA==Sequential OrganSequential Organ Failure Assessment score; qSOFA
Failure Assessment score; qSOFA==quick Sequential Organ Failurequick Sequential Organ Failure Assessment score.
Assessment score.
Table
Table 4. 4. The Modified Early Warning Score (MEWS), and National Early Warning The Modified Early Warning Score (MEWS), and National Early Warning (NEWS) (NEWS) Scores Scores
Modified
Modified Early Early Warning Warning Score Score (MEWS)(MEWS) S
Sccoorree 33 22 11 00 11 22 33
Respiratory rate (min
Respiratory rate (min--11)) ££8 8 99––114 4 1155––220 0 2211––2299 >>2929
Hear
Heart t rate (minrate (min--11)) ££40 40 4411––550 0 5511––11000 0 110011––11110 0 111111––112299 >>129129
Systolic BP (mmHg)
Systolic BP (mmHg) ££770 0 7711––880 0 8811––11000 0 110011––119999 ‡‡200200
Ur
Urinine e ououtptput ut (m(ml/l/kgkg/h/h) ) NiNill <<0.50.5
Temperature (
Temperature (C)C) ££35 35 3355..11––336 6 3636..11––338 8 3388..11––3388..55 ‡‡38.638.6
N
Neeuurroollooggiiccaal l AAlleerrt t RReeaaccttiinng g tto o vvooiicce e RReeaaccttiinng g tto o ppaaiin n UUnnrreessppoonnssiivvee
National
National Early Early Warning Warning Score Score (NEWS)(NEWS)
P
Phhyyssiioollooggiiccaal l ppaarraammeetteerrs s 3 3 2 2 1 1 0 0 1 1 2 2 33
Respiration rate
Respiration rate ££8 8 99––111 1 1122––220 0 2211––2244 ‡‡2525
Oxygen saturations
Oxygen saturations ££991 1 9922––993 3 9944––9955 ‡‡9696
A
Anny y ssuupppplleemmeennttaal l ooxxyyggeen n YYees s NNoo Temperature Temperature ££3355..0 0 3535..11––3366..0 0 3366..11––3388..0 0 3388..11––3399..00 ‡‡39.139.1 Systolic BP Systolic BP ££90 90 9911––10100 0 101011––11110 0 111111––212199 ‡‡220220 Heart rate Heart rate ££440 0 4411––550 0 5511––990 0 9911––11110 0 111111––113300 ‡‡131131 L
Leevveel l oof f ccoonnsscciioouussnneesss s A A VV..PP. . oor r UU
*The NEWS initiative flowed from the Royal College of Physicians’ NEWSDIG, and was jointly developed and funded in collaboration *The NEWS initiative flowed from the Royal College of Physicians’ NEWSDIG, and was jointly developed and funded in collaboration with the Royal College of Physicians, Royal College of Nursing, National Outreach Forum and NHS Training for Innovation.
with the Royal College of Physicians, Royal College of Nursing, National Outreach Forum and NHS Training for Innovation.
D D o o w w n n l l o o a a d d e e d d b b y y G G u u a a n n g g x x i i U U n n i i v v e e
r r s s i i t t y y f f o o r r N N a a t t i i o o n n
a a l l i i t t i i e e s s f f r r o o m m o o n n l l i i n n e e
. . l l i i e e b b e e r r t t p p u u b b c c . . o o m m a a t t 0 0 2 2 / / 1 1 6 6 / / 1 1 8 8 . . F F o o r r p p e e r r s s o o n n a a l l u u s s e e o o n n l l y y . .
(20
(20 mL/kmL/kg crystallg crystalloid in 2008; 30oid in 2008; 30 mL/kmL/kg in g in 2012 for treat-2012 for treat-ment of hypotension or elevated lactate) and discontinuation ment of hypotension or elevated lactate) and discontinuation of the 2008 sepsis management bundle (steroids, activated of the 2008 sepsis management bundle (steroids, activated protei
protein C, n C, glyceglycemic control, and mic control, and low plateau pressures inlow plateau pressures in mechanically ventilated patients).
mechanically ventilated patients). A
A globaglobal, l, prospeprospectivective, , observobservatioational nal qualiquality ty improvimprovementement study of compliance with the 2012 SSC bundles in patients study of compliance with the 2012 SSC bundles in patients wit
withh sevsevereere sepsepsissis oror sepseptictic shoshockck incincludludeded 1,71,79494 patpatienientsts fromfrom 62
62 coucountrntries,andies,and docdocumeumententedd thathatt oveoveralralll comcomplipliancancee waslow,waslow, at
at onlonlyy 19%for19%for thethree-thethree-houhourr bunbundledle,, andand 36%for36%for thesix-hothesix-hourur bun
bundledle.. HowHoweveever,r, SSCSSC bunbundledle comcomplipliancancee waswas assassociociateatedd witwithh aa 4040%% rereduductctioionn inin ththee ododdsds ofof dydyiningg inin hohospspititalal wiwithth ththee ththreree- e-hour bundle and 36% for the six-e-hour bundle [23].
hour bundle and 36% for the six-hour bundle [23].
The most recent guideline update was published in 2016 The most recent guideline update was published in 2016 [24] and includes new three-hour and six-hour SSC bundles [24] and includes new three-hour and six-hour SSC bundles (Table 6). The most recent SSC bundles focus on early (Table 6). The most recent SSC bundles focus on early an-tibiotic treatment and fluid resuscitation to be
tibiotic treatment and fluid resuscitation to be initiated withininitiated within three hours. Early identification of patients with sepsis, early three hours. Early identification of patients with sepsis, early intravenous fluid resuscitation, and early intravenous intravenous fluid resuscitation, and early intravenous antibi-otic administration are the mainstay of sepsis management. otic administration are the mainstay of sepsis management. Consistent in all of the SSC bundles is the Consistent in all of the SSC bundles is the recommenda-tion f
tion foror antantibiibiotioticc admiadminisnistrattrationion witwithinhin oneone houhourr ofof diadiagnognosissis of of se
sepsipsis.s. InIn aa ststududyy ofof 2828,15,1500 papatitienentsts wiwithth seseveverere sesepsipsiss anandd sepseptiticc
shock, in-hospital mortality was 19.7%, and delay in the first shock, in-hospital mortality was 19.7%, and delay in the first antibiotic administration was associated with increased risk of antibiotic administration was associated with increased risk of death [25].
death [25].
The major change from the 2012 SSC bundle is the removal The major change from the 2012 SSC bundle is the removal of early goal-directed therapy recommendations (resuscitation of early goal-directed therapy recommendations (resuscitation targets central venous pressure [CVP]
targets central venous pressure [CVP] ‡ ‡8, central venous oxy-8, central venous
oxy-gen saturation [ScVO
gen saturation [ScVO22]]‡‡ 70%, and 70%, and normalinormalization of lactate) inzation of lactate) in
the six-hour SSC bundle. The 2016 SSC bundle recommends the six-hour SSC bundle. The 2016 SSC bundle recommends serial re-assessment of volume status and tissue perfusion with serial re-assessment of volume status and tissue perfusion with dyn
dynamiamicc asseassessmessmentsnts ofof fluidfluid respresponsonsiveivenessness incincludludinging phyphysicasicall examination to evaluate for hypoperfusion, bedside examination to evaluate for hypoperfusion, bedside cardiovas-cular ultrasound, passive leg elevation, or fluid challenge. cular ultrasound, passive leg elevation, or fluid challenge.
The
The newnew SSCSSC guguideidelinlineses 20201616 alsalsoo recrecognognizeize ththatat wewe are are inin an era of
an era of ‘‘perso‘‘personalized’nalized’’ medicine and ‘‘one size does not ’ medicine and ‘‘one size does not fitfit all.’’ Therefore, the SSC bundle recommendations are not all.’’ Therefore, the SSC bundle recommendations are not meant to be implemented without interval re-evaluation. For meant to be implemented without interval re-evaluation. For example, in a patient with sepsis with severe hypoxemia and example, in a patient with sepsis with severe hypoxemia and acut
acute e resprespiratoiratory ry distdistress ress syndsyndrome or rome or hearheart t failfailure, ure, fluidfluid resuscitation of 30 mL/kg may not be appropriate and resuscitation of 30 mL/kg may not be appropriate and vaso-pressor or cardiotonic medications may be indicated to pressor or cardiotonic medications may be indicated to op-timize tissue perfusion [26]. We are beginning to determine timize tissue perfusion [26]. We are beginning to determine risk factors for patients who are not fluid responsive in septic risk factors for patients who are not fluid responsive in septic shoc
shock k (hea(heart rt failfailure, ure, hyphypotheothermiarmia, , immuimmunoconocomprommpromisedised,,
Table
Table 5. 5. Difference in the Surviving Sepsis Campaign Bundles Difference in the Surviving Sepsis Campaign Bundles, 2008 (, 2008 (leftleft)) vsvs. 2012 (. 2012 (rightright))
Sepsis resuscitati
Sepsis resuscitation on bundlebundle
To be accomplished as soon as possible and scored over To be accomplished as soon as possible and scored over
the first 6 hours: the first 6 hours: 1. Measure serum lactate. 1. Measure serum lactate.
2. Obtain blood cultures prior to antibiotic 2. Obtain blood cultures prior to antibiotic
administration. administration.
3. From the time of presentation, administer 3. From the time of presentation, administer
broad-spectrum antibiotics within 3 hours for ED admissions spectrum antibiotics within 3 hours for ED admissions and 1 hour for non-EDICU admissions.
and 1 hour for non-EDICU admissions. 4. In the event of hypotension and/or lactate
4. In the event of hypotension and/or lactate >>3636 mg/dmg/dL:L:
a) Delive
a) Deliver r an initiaan initial minimum of 20l minimum of 20 mL/kmL/kg of g of crystalloid (or colloid equivalent).
crystalloid (or colloid equivalent).
b) Apply vasopressors for hypotension that does not b) Apply vasopressors for hypotension that does not
respond to initial fluid resuscitation to maintain respond to initial fluid resuscitation to maintain mean arteria
mean arterial l presspressure ure (MAP)(MAP) >>6565 mm Hgmm Hg..
5. In the event of persistent hypotension despite fluid 5. In the event of persistent hypotension despite fluid
resuscitation (septic shock) and/or lactate
resuscitation (septic shock) and/or lactate >>44 mmolmmol/L/L
(36
(36 mg/dmg/dL):L):
a) Achieve central venous pressure (CVP) of a) Achieve central venous pressure (CVP) of >>8–8–
12mmHg. 12mmHg.
b) Achieve central venous oxygen saturation (ScvO b) Achieve central venous oxygen saturation (ScvO22))
of of >>70%.70%.
Sepsis management bundle Sepsis management bundle
To be accomplished as soon as possible and scored over To be accomplished as soon as possible and scored over
the first 24 hours: the first 24 hours:
1. Administer low-dose steroids for septic shock in 1. Administer low-dose steroids for septic shock in
accordance with a standardized ICU policy. accordance with a standardized ICU policy.
2. Administer drotrecogin alfa (activated) in accordance 2. Administer drotrecogin alfa (activated) in accordance
with a standardized ICU policy. with a standardized ICU policy.
3. Glucose control maintained above lower limit of 3. Glucose control maintained above lower limit of
normal, but
normal, but <<150150 mg/dmg/dl.l.
4. Maintain inspiratory plateau pressures at
4. Maintain inspiratory plateau pressures at <<30cm H30cm H22OO
for mechanically ventilated patients. for mechanically ventilated patients.
Surviving sepsis campaign bundles Surviving sepsis campaign bundles To be completed within 3 hours: To be completed within 3 hours: 1. Measure lactate level
1. Measure lactate level
2. Obtain blood cultures prior to administration of 2. Obtain blood cultures prior to administration of
antibiotics antibiotics
3. Administer broad spectrum antibiotics 3. Administer broad spectrum antibiotics 4. Administer 30
4. Administer 30 mL/kg crystalloimL/kg crystalloid for hypotension ord for hypotension or lactate
lactate ‡‡4 mmol/L4 mmol/L
To be completed within 6 hours: To be completed within 6 hours:
5. Apply vasopressors (for hypotension that does not 5. Apply vasopressors (for hypotension that does not respond to initial fluid resuscitation) to maintain a respond to initial fluid resuscitation) to maintain a mean arteria
mean arterial l presspressure ure (MAP)(MAP) ‡‡65mm Hg65mm Hg
6. In the event of persistent arterial hypotension despite 6. In the event of persistent arterial hypotension despite volume resuscitation (septic shock) or initial lactate volume resuscitation (septic shock) or initial lactate
‡
‡44 mmolmmol/L (3/L (366 mg/dmg/dL)L)
-Measure central venous pressure (CVP)* -Measure central venous pressure (CVP)*
-Measure central venous oxygen saturation (Scvo -Measure central venous oxygen saturation (Scvo22)*)*
7. Remeasure lactate if initial lactate was elevated* 7. Remeasure lactate if initial lactate was elevated*
*Targets for quantitative resuscitation included in the guidelines are CVP of
*Targets for quantitative resuscitation included in the guidelines are CVP of ‡‡88 mm Hg, Scmm Hg, Scvovo22 of of ‡‡70%, and normalization of lactate.70%, and normalization of lactate.
From: www.survivingsepsis.org From: www.survivingsepsis.org D D o o w w n n l l o o a a d d e e d d b b y y G G u u a a n n g g x x i i U U n n i i v v e e
r r s s i i t t y y f f o o r r N N a a t t i i o o n n
a a l l i i t t i i e e s s f f r r o o m m o o n n l l i i n n e e
. . l l i i e e b b e e r r t t p p u u b b c c . . o o m m a a t t 0 0 2 2 / / 1 1 6 6 / / 1 1 8 8 . . F F o o r r p p e e r r s s o o n n a a l l u u s s e e o o n n l l y y . .
To be completed within 3 hours To be completed within 3 hours
1. Measure lactate level. 1. Measure lactate level.
2. Obtain blood cultures prior to administration of antibiotics. 2. Obtain blood cultures prior to administration of antibiotics. 3. Administer broad spectrum antibiotics.
3. Administer broad spectrum antibiotics. 4. Administer 30
4. Administer 30 ml/kg crystalloid for hypotml/kg crystalloid for hypotension or lactateension or lactate ‡‡4 mmol/L.4 mmol/L.
‘‘Time of presentation’’ is defined as the time of triage in the emergency department or, if presenting from another care ‘‘Time of presentation’’ is defined as the time of triage in the emergency department or, if presenting from another care venue, from the earliest chart annotation consistent with all elements of severe sepsis or septic shock ascertained through venue, from the earliest chart annotation consistent with all elements of severe sepsis or septic shock ascertained through chart review.
chart review.
To be completed within 6 hours To be completed within 6 hours
5. Apply vasopressors (for hypotension that does not respond to initial fluid resuscitation) to maintain a mean arterial 5. Apply vasopressors (for hypotension that does not respond to initial fluid resuscitation) to maintain a mean arterial
press
pressure ure (MAP)(MAP) ‡‡6565 mm Hgmm Hg..
6. In the event of persistent hypotension after initial fluid administration (MAP
6. In the event of persistent hypotension after initial fluid administration (MAP <<6565 mm Hg) or mm Hg) or if initiaif initial lactatl lactate wase was ‡
‡44 mmolmmol/L, re-assess volume status and /L, re-assess volume status and tissutissue e perfuperfusion and sion and docudocument findingment findings s accoaccordinrding g to to TablTable e 1.1.
7. Re-measure lactate if initial lactate elevated. 7. Re-measure lactate if initial lactate elevated. Document
Document reassessment reassessment of of volume volume status status and and tissue tissue perfusion perfusion withwith
Either: Either:
Repeat focused exam (after initial fluid resuscitation) including vital signs, cardiopulmonary, capillary refill, pulse, andRepeat focused exam (after initial fluid resuscitation) including vital signs, cardiopulmonary, capillary refill, pulse, and
skin findings. skin findings.
Or two of the following: Or two of the following:
Measure CVP.Measure CVP.
Measure ScvOMeasure ScvO22..
Perform bedside cardiovascular ultrasound.Perform bedside cardiovascular ultrasound.
Perform dynamic assessment of fluid responsiveness with passive leg raise or fluid challenge.Perform dynamic assessment of fluid responsiveness with passive leg raise or fluid challenge.
From: www.survivingsepsis.org From: www.survivingsepsis.org
Table
Table 7. 7. Surviving Sepsis Campaign Guideline Changes Comparing Surviving Sepsis Campaign Guideline Changes Comparing 2012 2012 andand 2016 2016 Recommendations Recommendations
2
2001122 20201166
Seps
Sepsis dis definiefinition tion SysteSystemic mic manimanifestafestation tion of iof infectnfection ion plus plus suspesuspectedcted infection
infection
Severe sepsis: sepsis plus organ dysfunction Severe sepsis: sepsis plus organ dysfunction
Life-threatening organ dysfunction caused Life-threatening organ dysfunction caused
by dysregulated response to infection. by dysregulated response to infection. No severe sepsis definition
No severe sepsis definition Init
Initial resusciial resuscitatitation on At least 30 At least 30 mL/kmL/kg in g in the first 3the first 3 h; crystallh; crystalloid fluid (no oid fluid (no specspecific recommeific recommendatndation for ion for fluid type)fluid type).. Albumin if patients require substantial fluids
Albumin if patients require substantial fluids
Early goal-directed therapy protocolized care including Early goal-directed therapy protocolized care including
CVP, ScVO2. CVP, ScVO2. Normalize lactate Normalize lactate
Use dynamic resuscitation markers (passive Use dynamic resuscitation markers (passive
le
legg elelevevatatioion,n, TTTTE).E). TarTargegett MAMAPP 6565 mmmm HgHg.. Re-assess hemodyn
Re-assess hemodynamic status amic status to to guideguide resuscitation. Normalize lactate resuscitation. Normalize lactate V
Vaasosoprpreessssoors rs TaTargrgeet t MMAAP P 6655 mm mm HHgg
Norepinephrine vasopressor of choice; epinephrine if not at target MAP or vasopressin to reduce Norepinephrine vasopressor of choice; epinephrine if not at target MAP or vasopressin to reduce
norepinephrine requirement. Avoid dopamine in most patients. norepinephrine requirement. Avoid dopamine in most patients. St
Stereroioids ds OnOnly ly inindidicacateted d in in seseptptic ic shshocock k rerefrafractctorory y to to adadeqequauate te flufluidids s anand d vavasosoprpresessosorsrs Antibiotic
Antibiotic
administration administration
Administration of effective IV antimicrobial agents Administration of effective IV antimicrobial agents
within the first hour of recognition of septic shock and within the first hour of recognition of septic shock and severe sepsis without septic shock.
severe sepsis without septic shock. Initia
Initial empil empiric anric anti-infti-infectivectivee theraptherapy ofy of one orone or moremore drugsdrugs that have activity against all likely pathogens.
that have activity against all likely pathogens. Combi
Combinatinationon empiriempiricalcal theraptherapyy forfor neutroneutropenipenicc patipatientsents with severe sepsis and for patients with with severe sepsis and for patients with difficult-to-treat, multi-drug–resistant bacterial pathogens such treat, multi-drug–resistant bacterial pathogens such as
as Acinetobacter Acinetobacter and and Pseudomonas Pseudomonas spp. spp.
Antimicrobial regimen should be reassessed daily for Antimicrobial regimen should be reassessed daily for
potential deescalation. Use of low procalcitonin levels potential deescalation. Use of low procalcitonin levels or similar biomarke
or similar biomarkers rs to assist the to assist the cliniclinician in thecian in the discontinuation of empiric antibiotics in patients who discontinuation of empiric antibiotics in patients who initially appeared septic, but have no subsequent initially appeared septic, but have no subsequent evidence of infection
evidence of infection
We recommend that administration of IV We recommend that administration of IV
antimicrobials be initiated as soon as antimicrobials be initiated as soon as possi
possible after recognitble after recognition and ion and withwithin 1in 1 hh for both sepsis and septic shock.
for both sepsis and septic shock.
Initial IV broad-spectrum antibiotic agents to Initial IV broad-spectrum antibiotic agents to cover all potential pathogens. The addition cover all potential pathogens. The addition of a second gram-negative agent to the of a second gram-negative agent to the empiric regimen is recommended for empiric regimen is recommended for critically ill patients withsepsis at high risk critically ill patients withsepsis at high risk of infection with multi-drug–resistant of infection with multi-drug–resistant pathogens (e.g.,
pathogens (e.g., Pseudomonas, Pseudomonas, Acinetobacter
Acinetobacter , etc.) to increase, etc.) to increase the probability of at least one active the probability of at least one active agent being administered
agent being administered
May use procalcitonin to guide de-escalation May use procalcitonin to guide de-escalation
of antibiotic therapy. of antibiotic therapy. S
Soouurrcce e ccoonnttrrool l AcchA hiieevve e wwiitthhiin n 112h, 2h, iif f ffeeaassiibblle e AAcchhiieevve e aas s ssoooon n aas s mmeeddiiccaalllly y aannd d llooggiiccaallllyy feasible
feasible
CVP
CVP==cencentratral l venovenous us prepressussure; re; ScVScVOO22==cencentratral l venovenous us oxygoxygen en satsaturaurationtion; ; MAPMAP==meamean n artarterierial al prepressussure; re; TTETTE==transthoracictransthoracic
echocardiography; IV
echocardiography; IV==intravenous.intravenous.
122 122 D D o o w w n n l l o o a a d d e e d d b b y y G G u u a a n n g g x x i i U U n n i i v v e e
r r s s i i t t y y f f o o r r N N a a t t i i o o n n
a a l l i i t t i i e e s s f f r r o o m m o o n n l l i i n n e e
. . l l i i e e b b e e r r t t p p u u b b c c . . o o m m a a t t 0 0 2 2 / / 1 1 6 6 / / 1 1 8 8 . . F F o o r r p p e e r r s s o o n n a a l l u u s s e e o o n n l l y y . .
