SEPSIS, AND SEPTIC SHOCK Megan Dorsey, PGY-1 Pharmacy Practice - - PowerPoint PPT Presentation

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SEPSIS, AND SEPTIC SHOCK Megan Dorsey, PGY-1 Pharmacy Practice - - PowerPoint PPT Presentation

Dec 30, 2023 272 likes •615 views

EVALUATING APPROACHES TO REDUCE DELAY OF FIRST AND SECOND DOSE ANTIBIOTICS FOR PATIENTS ADMITTED FOR SEPSIS, SEVERE SEPSIS, AND SEPTIC SHOCK Megan Dorsey, PGY-1 Pharmacy Practice Resident Providence Alaska Medical Center Anchorage, AK IRB

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SLIDE 1

EVALUATING APPROACHES TO REDUCE DELAY OF FIRST AND SECOND DOSE ANTIBIOTICS FOR PATIENTS ADMITTED FOR SEPSIS, SEVERE SEPSIS, AND SEPTIC SHOCK

Megan Dorsey, PGY-1 Pharmacy Practice Resident Providence Alaska Medical Center Anchorage, AK

IRB status: Approved

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SLIDE 2

Disclosure Statement

  • Speaker: Megan Dorsey
  • Conflict of interest: None
  • Sponsorship: None
  • Propriety information or results of ongoing research is subject to different

interpretation

  • Speaker’s presentation is educational in nature and abides by the non-

commercial guidelines

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SLIDE 3

Learning Objectives

  • Discuss rationale and evidence for timely antibiotic administration in patients

with sepsis

  • Examine the effectiveness of preplanned interventions aimed at reducing time

to administration for 1st and 2nd dose antibiotics

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SLIDE 4

Providence Alaska Medical Center

  • Tertiary care community medical center in Anchorage, AK
  • Not for profit
  • Level II trauma center
  • Largest hospital in the state of Alaska
  • 402 Beds
  • 62 Emergency Department beds
  • 37 Adult ICU beds

http://akfmr.org/wp-content/uploads/2014/04/providence-hospital-in-anchorage_3028.jpg

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SLIDE 5

Pre-Test Assessment Questions

  • Per the Surviving Sepsis Campaign Guidelines, how soon should antibiotic therapy

be initiated on a patient presenting to the ED with suspected sepsis?

  • A. 30 minutes
  • C. 3 hours
  • B. 1 hour
  • D. 6 hours
  • Lapses in second dose antibiotic administration could potentially cause, which of

the following:

  • A. Decreased therapy efficacy
  • C. Risk of developing poor outcomes
  • B. Risk of developing resistance
  • D. All of the above
  • Preliminary data from this study done at Providence Alaska Medical Center, shows

a ____ decrease in late antibiotics following 3 planned interventions:

  • A. 21.6%
  • C. 19.8%
  • B. 5%
  • D. 11.2%
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SLIDE 6

Study Objectives

  • Examine the timing of first and second doses of antibiotics in patients diagnosed

with sepsis, severe sepsis, and septic shock admitted from the ED to an inpatient floor

  • Evaluate the effectiveness of process changes aimed at reducing delays in 1st and

2nd dose antibiotic administration

  • Identify areas of further improvement to help reduce further antibiotic delays
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SLIDE 7

Importance of Time to First Dose

  • Linear increase in mortality was associated with each hour delay in initial antibiotic therapy
  • “Hour-1 Bundle”
  • Measure lactate
  • Obtain cultures
  • Administer broad spectrum antibiotics
  • Start fluid resuscitation with 30 ml/kg of fluid (crystalloid preferred)
  • Begin vasopressors during/after resuscitation, if indicated

Ferrer, et al. Crit Care Med. 2014. Kumar, et al. Crit Care Med. 2006. Rhodes, et al. Crit Care Med. 2017

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SLIDE 8

Importance of Time to Second Dose

  • Limited data exists examining effects of delayed second dose antibiotics
  • One retrospective study, including 828 patients with sepsis
  • Major delays were associated with a greater risk of hospital mortality

(OR: 1.61, CI 1.01-2.57, p=0.046)

  • Increased odds of requiring mechanical ventilation in patients not mechanically

ventilated at time of second dose (OR 2.44, CI 1.27-4.69, p = 0.007).

  • Theoretical effects: decreased efficacy of therapy, increased risk of resistance

Leisman, et al. Crit Care Med. 2017. Martinez, et al. Antimicrob Agents Chemother. 2012.

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SLIDE 9

Methodology

  • Retrospective review of electronic health records of patients admitted from the

emergency department to an inpatient floor with sepsis, severe sepsis, or septic shock

  • 1st and 2nd dose antibiotic administration times were collected at 3 time periods:

Baseline Group

Start

Post- Minibag Group

Minibag Systems in Pyxis

Post- Meeting/ED RPh Group

Provider Meeting ED RPh Services

Pre-Interventions Post-Interventions

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SLIDE 10

Methodology

Inclusion Criteria

  • Admission to an inpatient floor from

the emergency department

  • Diagnosis of sepsis, severe sepsis, or

septic shock

  • Age > 18 years old
  • Administration of at least 2 doses of

an antibiotic with a dosing interval < 24 hours

Exclusion Criteria

  • Age < 18 years old
  • Transfer from an outside facility
  • Pregnancy
  • Incarceration
  • Failure to meet inclusion criteria
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SLIDE 11

Sepsis Definitions

  • Sepsis: Evidence or suspicion of infection with two or more of the following:
  • Temp > 38.3 ˚C or < 36 ˚C
  • HR > 90 bpm
  • RR > 20 bpm
  • WBC > 12,000 or < 4,000 or > 10% immature bands
  • Severe Sepsis: Sepsis (per above criteria) + one of the following:
  • Platelets < 100,000
  • Coagulopathy (INR > 1.5 or PTT > 60 sec)
  • PaO2/FiO2 < 250 (or < 200 if pneumonia)
  • Lactate > 2 mmol/L
  • SBP < 90 mmHg or MAP < 65 mmHg
  • SCr > 2 mg/dL or UOP < 0.5 ml/kg/hr for 2 consecutive hours
  • Total bilirubin > 2 mg/dL
  • Septic Shock: Severe Sepsis (per above criteria) + hypotension despite fluid resuscitation

Levy, et al. Crit Care Med. 2003.

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SLIDE 12

437 patients screened 188 patients excluded

  • 77 did not have sepsis
  • 50 transferred from OSF
  • 42 did not have 2 doses of same antibiotic
  • 19 did not receive ED antibiotics

249 patients included

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SLIDE 13

437 patients screened 188 patients excluded

  • 77 did not have sepsis
  • 50 transferred from OSF
  • 42 did not have 2 doses of same antibiotic
  • 19 did not receive ED antibiotics

249 patients included 380 antibiotics included

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SLIDE 14

437 patients screened 188 patients excluded

  • 77 did not have sepsis
  • 50 transferred from OSF
  • 42 did not have 2 doses of same antibiotic
  • 19 did not receive ED antibiotics

249 patients included 380 antibiotics included 500 antibiotic administrations

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SLIDE 15

437 patients screened 188 patients excluded

  • 77 did not have sepsis
  • 50 transferred from OSF
  • 42 did not have 2 doses of same antibiotic
  • 19 did not receive ED antibiotics

249 patients included 380 antibiotics included 500 antibiotic administrations Pre-Implementations N=250 Post-Implementations N=250 Post-Minibag N=94 Post ED RPh/Meeting N=156

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SLIDE 16

Pre-Interventions N=250 Post-Interventions N=250 P-Value Gender

  • Female
  • Male

126 (50.4%) 124 (49.6%) 130 (52%) 120 (48%) 0.72 Age 61.5 + 13.6 56.7 + 13.5 0.29 Diagnosis

  • Sepsis
  • Severe Sepsis
  • Septic Shock

80 (32%) 129 (51.6%) 41 (16.4%) 109 (43.6%) 112 (44.8%) 29 (11.6%) 0.007 0.13 0.12 Inpatient Units

  • Med/Surg/Ortho
  • PCU
  • ICU
  • CTICU/CICU
  • IMCU
  • Other

67 (26.8%) 79 (31.6%) 43 (17.2%) 21 (8.4%) 24 (9.6%) 16 (6.4%) 105 (42%) 49 (19.6%) 43 (17.2%) 17 (6.8%) 18 (7.2%) 18 (7.2%) 0.003 0.002 1 0.44 0.33 0.72 Antibiotics

  • Piperacillin/tazobactam
  • Ceftriaxone
  • Azithromycin
  • Cefepime
  • Cefazolin
  • Clindamycin

54 (21.6%) 43(17.2%) 41 (16.4%) 27 (10.8%) 6 (2.4%) 1 (0.4%) 85 (34%) 78 (31.2%) 28 (11.2%) 11 (4.4%) 4 (1.6%) 17 (6.8%) 0.09 0.06 0.002 0.007 0.35 <0.001

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SLIDE 17

Pre-Interventions N=250 Post-Interventions N=250 P-Value Gender

  • Female
  • Male

126 (50.4%) 124 (49.6%) 130 (52%) 120 (48%) 0.72 Age 61.5 + 13.6 56.7 + 13.5 0.29 Diagnosis

  • Sepsis
  • Severe Sepsis
  • Septic Shock

80 (32%) 129 (51.6%) 41 (16.4%) 109 (43.6%) 112 (44.8%) 29 (11.6%) 0.007 0.13 0.12 Inpatient Units

  • Med/Surg/Ortho
  • PCU
  • ICU
  • CTICU/CICU
  • IMCU
  • Other

67 (26.8%) 79 (31.6%) 43 (17.2%) 21 (8.4%) 24 (9.6%) 16 (6.4%) 105 (42%) 49 (19.6%) 43 (17.2%) 17 (6.8%) 18 (7.2%) 18 (7.2%) 0.003 0.002 1 0.44 0.33 0.72 Antibiotics

  • Piperacillin/tazobactam
  • Ceftriaxone
  • Azithromycin
  • Cefepime
  • Cefazolin
  • Clindamycin

54 (21.6%) 43(17.2%) 41 (16.4%) 27 (10.8%) 6 (2.4%) 1 (0.4%) 85 (34%) 78 (31.2%) 28 (11.2%) 11 (4.4%) 4 (1.6%) 17 (6.8%) 0.09 0.06 0.002 0.007 0.35 <0.001

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SLIDE 18

Data Analysis

  • First Dose “Late”: dose administered more than 1 hour from ED admission
  • Antibiotics were excluded if ordered after another antibiotic was already given
  • Second Dose “Late”: time between first and second dose was either

> 25% of the antibiotic dosing interval

OR

> 2 hours

Primary Endpoint Reduction in number of aggregate late 1st and 2nd dose antibiotics between the pre- and post- intervention groups

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SLIDE 19

Aggregate Late 1st or 2nd Doses

Pre-Interventions N=250 Post Interventions N=250 p-value 121 (48%) 97 (39%) 0.03

0% 10% 20% 30% 40% 50% 60% 70% Pre-Intervention Post-Intervention 48% 39% 52% 61% Late On-time

  • Excluded vancomycin

doses due to variable kinetics

  • 19.8% decrease in late

doses between the groups

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SLIDE 20

Secondary Analysis

Pre-Interventions Post-Interventions p-value Number of Late 1st Doses 87 (82.1%) 66 (61.1%) <0.001 Number of Late 2nd Doses 34 (23.6%) 31 (21.8%) 0.719

0% 10% 20% 30% 40% 50% 60% 70% 80% 90% Pre-Intervention Post-Intervention 82% 61% 18% 39% Late On-time 0% 10% 20% 30% 40% 50% 60% 70% 80% Pre-Intervention Post-Intervention 24% 22% 76% 78% Late On-time

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SLIDE 21

Secondary Analysis

Pre-Interventions Post-Intervention Difference (95% CI) p-value Average Delay of 1st and 2nd Doses 3.01 + 1.89 1.93 + 1.93 1.09 (0.78-1.38) <0.001 Average Delay to 1st Dose 2.49 + 1.43 1.43 + 1.95 0.71 (0.25-1.17) 0.003 Average Delay to 2nd Dose 3.53 + 2.21 2.09 + 1.09 1.44 (1.03-1.84) <0.001

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SLIDE 22

Secondary Analysis

Number of Late ( >1 hours from door to dose) and On-time doses over study period based on drug

100% 100% 100% 100% 90% 90% 75% 71% 68% 62% 50% 33% 0% 20% 40% 60% 80% 100% 120%

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SLIDE 23

Secondary Analysis

Number of Late ( >1 hours from door to dose) and On-time doses over study period based on drug

100% 100% 100% 100% 90% 90% 75% 71% 68% 62% 50% 33% 0% 20% 40% 60% 80% 100% 120%

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SLIDE 24

Secondary Analysis

Number of Late ( >1 hours from door to dose) and On-time doses over study period based on drug

100% 100% 100% 100% 90% 90% 75% 71% 68% 62% 50% 33% 96% 0% 20% 40% 60% 80% 100% 120%

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SLIDE 25

Secondary Analysis

Dosing Interval (hours) Average Delay to Second Dose % of Late Doses 4 2.48 hours 46.9% (15/24) 6 1.11 hours 33.3% (1/3) 8 3.99 hours 17.9% (5/28) 12 3.68 hours 20% (1/5) 24 4.52 hours 15.8% (12/76)

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SLIDE 26

Secondary Analysis

  • Patient’s admitted to the

CTICU/CICU had the largest % of late second antibiotic administrations delays

  • 36.3% of antibiotics were “late”

0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100% On-time Late

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SLIDE 27

Conclusions

  • These are preliminary results
  • Pre-planned interventions appear to provide a statistically significant reduction in

number of late 1st and 2nd dose antibiotics

  • 1st dose analysis showed statistically significant reduction in number of late doses
  • 2nd doses analysis did not appear to trend toward a reduction in number of late doses
  • There appears to be a significant reduction in average delay in hours between the

two groups for 1st and 2nd dose

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SLIDE 28

Limitations

1.

Retrospective

2.

Single-center

3.

Small sample size

4.

Unequal baseline characteristics

5.

Only included patient’s who received at least 2 doses of the same antibiotic

6.

Vancomycin data excluded from current analysis

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SLIDE 29

Discussion

  • Further analysis must be done to evaluate and identify potential causes of delays:
  • Pharmacy order verification delays
  • Pharmacy delivery delays
  • Nursing administration delays
  • Missed order continuations upon admission to unit
  • Further analysis into vancomycin delays and causes
  • Future projects could be conducted examining antibiotic appropriateness and

timing of antibiotics not limited to two doses of same antibiotic

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SLIDE 30

Post-Test Assessment Questions

  • Per the Surviving Sepsis Campaign Guidelines, how soon should antibiotic therapy

be initiated on a patient presenting to the ED with suspected sepsis?

  • A. 30 minutes
  • C. 3 hours
  • B. 1 hour
  • D. 6 hours
  • Lapses in second dose antibiotic administration could potentially cause, which of

the following:

  • A. Decreased therapy efficacy
  • C. Risk of developing poor outcomes
  • B. Risk of developing resistance
  • D. All of the above
  • Preliminary data from this study done at Providence Alaska Medical Center, shows

a ____ decrease in late antibiotics following 3 planned interventions:

  • A. 21.6%
  • C. 19.8%
  • B. 5%
  • D. 11.2%
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SLIDE 31

Post-Test Assessment Questions

  • Per the Surviving Sepsis Campaign Guidelines, how soon should antibiotic therapy

be initiated on a patient presenting to the ED with suspected sepsis?

  • A. 30 minutes
  • C. 3 hours
  • B. 1 hour
  • D. 6 hours
  • Lapses in second dose antibiotic administration could potentially cause, which of

the following:

  • A. Decreased therapy efficacy
  • C. Risk of developing poor outcomes
  • B. Risk of developing resistance
  • D. All of the above
  • Preliminary data from this study done at Providence Alaska Medical Center, shows

a ____ decrease in late antibiotics following 3 planned interventions:

  • A. 21.6%
  • C. 19.8%
  • B. 5%
  • D. 11.2%
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SLIDE 32

Acknowledgements

Dominique Lauten, Pharm.D., MPH

  • Clinical Pharmacist – Emergency Department
  • Providence Alaska Medical Center

Elaine Reale, Pharm.D.

  • Pharmacy Clinical Director, Residency Program Director
  • Providence Alaska Medical Center
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SLIDE 33

References

  • Ferrer R, Martin-Loeches I, Phillips G, et al. Empiric antibiotic treatment reduces mortality in severe sepsis and septic

shock from the first hour: results from a guideline-based performance improvement program. Crit Care Med 2014; 42(8):1749-1755.

  • Kumar A, Roberts D, Wood KE, et al. Duration of hypotension before initiation of effective antimicrobial therapy is the

critical determinant of survival in human septic shock. Crit Care Med 2006;34(6):1589-1598.

  • Leisman D, Huang V, Zhou Q, et al. Delayed second dose antibiotics for patients admitted from the emergency

department with sepsis: prevalence, risk factors, and outcomes. Crit Car Med 2017;45(6):956-965.

  • Levy LM, Fink MP, Marshell JC, et at. 2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definition Conference. Crit

Care Med 2003;31(4):1250-6.

  • Martinez MN, Papich MG, Drusano GL. Dosing regimen matters: the importance of early intervention and rapid

attainment of the pharmacokinetic/pharmacodynamic target. Antimicrob Agents Chemother 2012;56(6):2795-2805.

  • Rhodes A, Evans LE, AlhazzaniW, et al. Surviving Sepsis Campaign: International Guidelines for the Management of

Sepsis and Septic Shock: 2016. Crit Care Med. 2017;45(3):486-552.

  • Singer B. Quality assessment of delayed second dose antibiotics for patients admitted to the intensive care unit with
  • sepsis. Unpublished Manuscript. 2018.