ABSTRACT
5
Anand Kumar, Daniel Roberts, Kenneth Wood, Bruce Light, Joseph E. Parrillo, Satendra Sharma, Robert Suppes, Daniel Feinstein, Sergio Zanotti, Leo Taibert, David Gurka, Aseem Kumar, and Mary Cheang ABSTRACT Background. Current guidelines recommend antimicrobial initiation within one hour of presentation of severe sepsis and septic shock but no clinical studies are available to support this recommendation. Objective: To determine the prevalence and impact on mortality of delays in initiation of effective antimicrobial therapy from initial onset of recurrent/persistent hypotension of septic shock. Design, Setting and Patients: A retrospective cohort study using the medical records of 2731 adult patients with septic shock spread among 14 intensive care units (4 medical, 4 surgical, 6 mixed medical/surgical) and 10 hospitals (4 academic, 6 community) in Canada and the United States between July 1989 and June 2004 was performed. Main Outcome Measure: Survival to hospital discharge. Results: Among the 2154 septic shock patients (78.9% total) who received effective antimicrobial therapy only after the onset of antimicrobial effective for isolated or suspected pathogens within the first hour of documented hypotension was associated with a survival rate of 79.9%. Each hour of delay in antimicrobial administration over the ensuing 6 hours was associated with an average decrease in survival of 7.6%. By the 2 nd hour after onset of persistent/recurrent hypotension, in-hospital mortality was significantly increased relative to receiving therapy within the first hour (odds ratio 1.67; 95% confidence interval, 1.12-2.48). In multivariate analysis (including APACHE II score and therapeutic variables), time to initiation of effective antimicrobial therapy was the single strongest predictor of outcome. Median time to effective antimicrobial therapy was 6 hours (25-75 th percentile, 2.0-15.0 hrs.) Conclusion: Effective antimicrobial administration within the first hour of documented hypotension is associated with increased survival to hospital discharge in The Duration of Hypotension Prior to Initiation of Effective Antimicrobial Therapy is the Critical Determinant of Survival in Human Septic Shock
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The Duration of Hypotension Prior to Initiation of Effective Antimicrobial Therapy is the Critical Determinant of Survival in Human Septic Shock. - PowerPoint PPT Presentation
Transcript of ABSTRACT
Anand Kumar, Daniel Roberts, Kenneth Wood, Bruce Light, Joseph E. Parrillo, Satendra Sharma, Robert Suppes, Daniel Feinstein, Sergio Zanotti, Leo Taibert, David Gurka,
Aseem Kumar, and Mary Cheang
ABSTRACT Background. Current guidelines recommend antimicrobial initiation within one hour of presentation of severe sepsis and septic shock but no clinical studies are available to support this recommendation. Objective: To determine the prevalence and impact on mortality of delays in initiation of effective antimicrobial therapy from initial onset of recurrent/persistent hypotension of septic shock.Design, Setting and Patients: A retrospective cohort study using the medical records of 2731 adult patients with septic shock spread among 14 intensive care units (4 medical, 4 surgical, 6 mixed medical/surgical) and 10 hospitals (4 academic, 6 community) in Canada and the United States between July 1989 and June 2004 was performed.Main Outcome Measure: Survival to hospital discharge.Results: Among the 2154 septic shock patients (78.9% total) who received effective antimicrobial therapy only after the onset of recurrent or persistent hypotension, a strong relationship between the delay in effective antimicrobial initiation and in-hospital mortality was noted (adjusted odds ratio 1.119 [per hour delay], 95% confidence interval 1.103-1.136, p<0.0001). Administration of an
antimicrobial effective for isolated or suspected pathogens within the first hour of documented hypotension was associated with a survival rate of 79.9%. Each hour of delay in antimicrobial administration over the ensuing 6 hours was associated with an average decrease in survival of 7.6%. By the 2nd hour after onset of persistent/recurrent hypotension, in-hospital mortality was significantly increased relative to receiving therapy within the first hour (odds ratio 1.67; 95% confidence interval, 1.12-2.48). In multivariate analysis (including APACHE II score and therapeutic variables), time to initiation of effective antimicrobial therapy was the single strongest predictor of outcome. Median time to effective antimicrobial therapy was 6 hours (25-75th percentile, 2.0-15.0 hrs.)Conclusion: Effective antimicrobial administration within the first hour of documented hypotension is associated with increased survival to hospital discharge in adult patients with septic shock. Despite a progressive increase in mortality with increasing delays, only 50% pf septic shock patients receive effective antimicrobial therapy within 6 hours of documents hypotension. (Crit Care Med 2006;34(6):1589-1596
The Duration of Hypotension Prior to Initiation of Effective Antimicrobial Therapy is the Critical
Determinant of Survival in Human Septic Shock
The Duration of Hypotension Prior to Initiation of Effective Antimicrobial Therapy is the Critical
Determinant of Survival in Human Septic Shock
0-0-.49
0.5-.99
1-1.99
2-2.99
3-3.99
4-4.99
5-5.99
6-8.99
9-11.99
12-23.99
24-35.99
>36
1.0
0.8
0.6
0.4
0.2
0.0
Survival fraction
Cumulative effective antimicrobial initiation
Time from hypotension onset (hrs)
Fra
cti
on
of
tota
l p
atie
nts
Cumulative effective antimicrobial initiation following onset of septic shock-associated hypotension and associated survival. X axis represents time (hrs) following first
documentation of septic shock-associated hypotension.
The Duration of Hypotension Prior to Initiation of Effective Antimicrobial Therapy is the Critical
Determinant of Survival in Human Septic Shock
The Duration of Hypotension Prior to Initiation of Effective Antimicrobial Therapy is the Critical
Determinant of Survival in Human Septic Shock
Kumar et al. Crit Care Med 2006;34(6)1589-1596
100
10
1
Time (hrs)
1-1.99
2-2.99
3-3.99
4-4.99
5-5.99
6-8.99
9-11.99
12-23.99
24-35.99
>36
Od
ds
Rat
io o
f D
eath
(95%
Co
nfi
den
ce I
nte
rval
)
The Duration of Hypotension Prior to Initiation of Effective Antimicrobial Therapy is the Critical
Determinant of Survival in Human Septic Shock
The Duration of Hypotension Prior to Initiation of Effective Antimicrobial Therapy is the Critical
Determinant of Survival in Human Septic Shock Mortality risk (expressed as adjusted odds ratio of death) with increasing delays in initiation of
effective antimicrobial therapy. Bars represent 95% confidence interval. Increased risk of death is already present by the 2nd hour post-hypotension onset (compared to the first hour post-hypotension). The risk of death continues to climb through to > 36 hours post-hypotension onset.
Kumar et al. Crit Care Med 2006;34(6)1589-1596
N
2154
1695
459
1546
608
769
1385
1242
912
584
768
131
838
230
641
156
1.31.21.11.0
all
documented
suspected
culture +
culture -
bacteremia +
bacteremia -
community
nosocomial
gram +
gram -
fungal
respiratory
urinary tract
Intra-abdominal
skin/soft tissue
Relationship of antimicrobial delay to hospital mortality in
major subgroups (expressed as adjusted odds ratio of death with time as a continuous variable). Bars represent 95% confidence intervals. All major subgroups demonstrate a highly significant increase in mortality risk with
increasing delays in administration of effective
antimicrobial therapy following onset of sepsis-associated
hypotension. For the overall group, mortality risk increases approximately 12% every hour
relative to the risk in the previous hour. P values <0.0001
for all subgroups.
The Duration of Hypotension Prior to Initiation of Effective Antimicrobial Therapy is the Critical
Determinant of Survival in Human Septic Shock
The Duration of Hypotension Prior to Initiation of Effective Antimicrobial Therapy is the Critical
Determinant of Survival in Human Septic Shock
Kumar et al. Crit Care Med 2006;34(6)1589-1596
Septic Shock: Timing of Antibiotics
Kumar Crit Care Med 2006
0.00.0
.20.20
.40.40
.60.60
.80.80
1.001.00
% Survival
% Total receiving antibiotics
0 - .5
.5 – 1.01 - 2 2 - 3 3-4 4 - 5 5 - 6 6 - 9 9 - 1
212 - 2
424 - 3
6> 36
PercentPercent
Time, hrsTime, hrs
14 ICUs; n = 2,731
Only 50% of patients in Septic Shock
received antibiotics w/in 6 hrs.
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