fast administration of IV antibiotics in patients arriving to care with Sepsis to decrease risk of progression to septic shock

1. DELAYED ANTIBIOTIC ADMINISTRATION AND RISK OF SEPTIC
SHOCK
Ivan De Paz, MD

2. EPIDEMIOLOGY
Understanding the true burden of sepsis is complicated by many
factors
There are a lack of reliable sepsis incidence and prevalence data.
This is due to the absence of a consistent definition for sepsis and
differences in coding practice between professionals and
organizations
Inada-Kim M. Introducing the suspicion of sepsis insights dashboard.
Royal College of Pathologists Bulletin. 2019 Apr;186;109 2

3.  As sepsis represents the
negative evolution of any
infection when not diagnosed
early enough or not treated
effectively, its prevention
and appropriate management
are the cornerstone of any
strategy that aims to control this
disorder
Global report on the epidemiology and burden of
sepsis, WHO 2020
3

5. BURDEN OF SEPSIS WORLDWIDE

6. Global, regional, and national sepsis
incidence and mortality,1990–2017:
analysis for the Global Burden of
Disease Study

7. FACTS
 In 2017 48.9 million of cases of sepsis globally
 67 % was due to underlying infection
 32 % injuries and noncommunicable diseases
 In 2017, the largest contributors to sepsis incidence and mortality
among all age groups were diarrhoeal diseases and lower
respiratory infections, respectively
Global, regional, and national sepsis incidence and mortality,1990–
2017: analysis for the Global Burden of Disease Study
7

8. THIRD INTERNATIONAL CONSENSUS DEFINITIONS FOR
SEPSIS AND SEPTIC SHOCK (SEPSIS-3) (2016)
SEPSIS
 Life-threatening organ dysfunction caused by a dysregulated host
response to infection
8

9. SEPTIC SHOCK
 Septic shock is a subset of sepsis in which particularly
profound circulatory, cellular, and metabolic abnormalities
are associated with a greater risk of mortality than with
sepsis alone
 A patient with a clinical construct of sepsis with persisting
hypotension requiring vasopressors to maintain a MAP > 65 mmhg
and having a serum lactate level > 2 mmol/L (18 mg/dl) despite
adequate volume resuscitation
9

10. 10

11. DOES SEPSIS
HAVE A FACE?
11
A person at risk for sepsis

12.  By the time the diagnosis becomes obvious, with multiple
abnormal physiological parameters, risk of mortality is very high
12

13. N Engl J Med 2017;376:2235-44.
13

14. ABSTRACT
N Engl J Med 2017;376:2235-44
14
 We studied data from patients with sepsis and septic shock that were reported to the New York State
Department of Health from April 1, 2014, to June 30, 2016. Patients had a sepsis protocol initiated
within 6 hours after arrival in the emergency department and had all items in a 3-hour bundle of care
for patients with sepsis (i.e., blood cultures, broad-spectrum antibiotic agents, and lactate
measurement) completed within 12 hours. Multilevel models were used to assess the associations
between the time until completion of the 3-hour bundle and risk-adjusted mortality. We also examined
the times to the administration of antibiotics and to the completion of an initial bolus of intravenous
fluid.
Background
Methods
 In 2013, New York began requiring hospitals to follow protocols for the early identification and
treatment of sepsis

15. N Engl J Med 2017;376:2235-44
15

16. the completion of the 3-hour bundle at 6 hours
was associated with mortality that was
approximately 3 percentage points higher than
the mortality associated with completion of the
bundle within the first hour
N Engl J Med 2017;376:2235-44 16

17. N Engl J Med 2017;376:2235-44
17
Patients who received
antibiotics in hours 3
through 12 had 14%
higher odds of in-hospital
death than those who
received antibiotics within
3 hours

18. RESULTS
N Engl J Med 2017;376:2235-44
18
 Among 49,331 patients at 149 hospitals, 40,696 (82.5%) had the 3-hour
bundle completed within 3 hours. The median time to completion of the 3-
hour bundle was 1.30 hours (interquartile range, 0.65 to 2.35), the median
time to the administration of antibiotics was 0.95 hours (interquartile range,
0.35 to 1.95), and the median time to completion of the fluid bolus was 2.56
hours (interquartile range, 1.33 to 4.20). Among patients who had the 3-
hour bundle completed within 12 hours, a longer time to the completion of
the bundle was associated with higher risk-adjusted in-hospital mortality
(odds ratio, 1.04 per hour; 95% confidence interval [CI], 1.02 to 1.05;
P<0.001) as was a longer time to the administration of antibiotics (odds
ratio, 1.04 per hour; 95% CI, 1.03 to 1.06; P<0.001)

19. Roshan Bisarya, Xing Song, John Salle, Mei Liu, Anurag Patel, Steven Q. Simpson,
Antibiotic Timing and Progression to Septic Shock Among Patients in the ED With Suspected Infection,Chest,Volume 161, Issue 1,
2022,
19

20. ANTIBIOTIC TIMING AND PROGRESSION TO SEPTIC SHOCK
AMONG PATIENTS IN THE ED WITH SUSPECTED INFECTION
 Retrospective study
 University of Kansas Hospital
 All adults who sought treatment at the ER with suspected infection
 Suspected infection was defined as patients having blood or body fluid
cultures obtained and antimicrobials initiated within 4h of one another
 Progression to septic shock was defined as vasopressor initiated > 3 h
after triage
Roshan Bisarya, Xing Song, John Salle, Mei Liu, Anurag Patel, Steven Q. Simpson,
Antibiotic Timing and Progression to Septic Shock Among Patients in the ED With Suspected Infection,Chest,Volume 161, Issue 1,
January 2022,
20

21. ANTIBIOTIC TIMING AND PROGRESSION TO SEPTIC SHOCK
AMONG PATIENTS IN THE ED WITH SUSPECTED INFECTION
Roshan Bisarya, Xing Song, John Salle, Mei Liu, Anurag Patel, Steven Q. Simpson,
Antibiotic Timing and Progression to Septic Shock Among Patients in the ED With Suspected Infection,Chest,Volume 161, Issue 1,
January 2022,
21
1.8 h

22. ANTIBIOTIC TIMING AND PROGRESSION TO SEPTIC SHOCK AMONG PATIENTS IN THE ED WITH
SUSPECTED INFECTION
22
P/T
Ceftria

23. ANTIBIOTIC TIMING AND
PROGRESSION TO SEPTIC SHOCK
AMONG PATIENTS IN THE ED WITH
SUSPECTED INFECTION
23

24. ANTIBIOTIC
TIMING AND
PROGRESSION
TO SEPTIC
SHOCK AMONG
PATIENTS IN
THE ED WITH
SUSPECTED
INFECTION
24
The greatest
increase in %
of patients
progressing to
SS occurs
with
antimicrobials
administered
in the first 5 h
88

25. Roshan Bisarya, Xing Song, John Salle, Mei Liu, Anurag Patel, Steven Q. Simpson,
otic Timing and Progression to Septic Shock Among Patients in the ED With Suspected Infection,
Chest,Volume 161, Issue 1,
January 2022, 25

26. MORE RESULTS FROM THIS STUDY
 When adjusted for severity of illness, each hour delayed until initial
antimicrobial administration was associated with a 4% increase in
progression to septic shock for every 1 hour up to 24 h from triage
 Patients with vague symptoms experience delayed administration
of antibiotics and a higher risk of mortality
26
Roshan Bisarya, Xing Song, John Salle, Mei Liu, Anurag Patel, Steven Q. Simpson,
Antibiotic Timing and Progression to Septic Shock Among Patients in the ED With Suspected Infection,
Chest,Volume 161, Issue 1,
January 2022,

27.  A substantial proportion of patients demonstrated shock despite
receiving antibiotics within 1 hour, suggesting that some patients have
entered a trajectory of shock before entering the ED
 The duration of sepsis before presentation to the ED is a key factor
 A principle of quickly administering antibiotics as soon as infection is
recognized seems to be appropriate
 Delays in first antimicrobial administration in patients with suspected
infection are associated with rapid increases in likelihood of progression
to septic shock
Roshan Bisarya, Xing Song, John Salle, Mei Liu, Anurag Patel, Steven Q. Simpson,
Antibiotic Timing and Progression to Septic Shock Among Patients in the ED With Suspected Infection,
Chest,Volume 161, Issue 1,
January 2022,
27
THINGS TO CONSIDER

28. Im Y, Kang D, Ko RE, Lee YJ, Lim SY, Park S, Na SJ, Chung CR, Park
MH, Oh DK, Lim CM, Suh GY; Korean Sepsis Alliance (KSA) investigators.
Time-to-antibiotics and clinical outcomes in patients with sepsis and septic
shock: a prospective nationwide multicenter cohort study. Crit Care. 2022
Jan 13;26(1):19. doi: 10.1186/s13054-021-03883-0. PMID: 35027073;
PMCID: PMC8756674.
28

29. Yealy DM, Mohr NM, Shapiro NI, Venkatesh A, Jones AE, Self WH. Early
Care of Adults With Suspected Sepsis in the Emergency Department and
Out-of-Hospital Environment: A Consensus-Based Task Force Report. Ann
Emerg Med. 2021 Jul;78(1):1-19. doi:
10.1016/j.annemergmed.2021.02.006. Epub 2021 Apr 9. Erratum in: Ann
Emerg Med. 2021 Sep;78(3):464. PMID: 33840511.
29

30. A CONCEPT THAT SHOULD BE IN YOUR HEADS ALREADY
Surviving Sepsis Campaign: International Guidelines for Management
of Sepsis and Septic Shock 2021. Crit Care Med. 2021 Nov
1;49(11):e1063-e1143 30
The mortality reduction associated with early
antimicrobials appears strongest in patients
with septic shock
For patients with septic shock, delay of
antibiotic administration is associated with
increased mortality

31. MANAGING AND TREATING SUSPECTED SEPSIS IN ACUTE
HOSPITAL SETTINGS
31

32. COULD THIS BE SEPSIS?
 Extremes of Age- early childhood and elderly
 Immunosupression
 Multidrug resistant Infection
 Recent surgery
 Indwelling catheters
 Any breach of skin integrity
 Misuse of IV drugs
32

33. Royal College of Physicians. National Early Warning Score (NEWS) 2:
Standardising the assessment of
acute-illness severity in the NHS. Updated report of a working party.
London: RCP, 2017
33
 NEWS2 has received formal endorsement from NHS England and
NHS Improvement to become the early warning system for
identifying acutely ill patients – including those with sepsis – in
hospitals in England

34. SEPSIS TREATMENT ALGORITHM
BMJ Best practice- NHS England. Sepsis guidance implementation
advice for adults. September 2017 [internet publication] 34

35.  Within 1 hour of the risk being recognised for patients with critical
illness on presentation (including those with septic shock, sepsis
associated with rapid deterioration, or a NEWS2 score ≥7): take
two sets of blood cultures, measure serum lactate on a blood gas,
and assess the patient’s hourly urine output; give intravenous
broad-spectrum antibiotics (after taking blood cultures) if there is
evidence of a bacterial infection, give intravenous fluids if there is
any sign of circulatory insufficiency, and give oxygen if needed.
35

36. CARRY OUT A VENOUS BLOOD TEST FOR THE FOLLOWING:
 － blood gas including glucose and lactate measurement
 － blood culture
 － full blood count
 － C-reactive protein
 － urea and electrolytes
 － creatinine
 － a clotting screen
NICE Sepsis: recognition, diagnosis and early management July
2016
36

37. ENSURE YOU HAVE A MECHANISM IN PLACE TO
ADMINISTER ANTIBIOTICS TO ANY HIGH-RISK PATIENT (EITHER AT
YOUR PRACTICE OR VIA THE AMBULANCE SERVICE) IF THE
TRANSFER TIME TO HOSPITAL IS LIKELY TO BE MORE THAN 1 HOUR

38. SEPSIS IS A TIME DEPENDENT MEDICAL EMERGENCY!
38

39. The key to improving
outcomes is early
recognition and
prompt treatment, as
appropriate, of
patients with
suspected or
confirmed infection
who are deteriorating
and at risk of organ
dysfunction
39

41. THANK YOU
Ivan De Paz
drivandepaz.mejia@yahoo.com
41