Assessment of Outcomes in Septic Shock and Severe Sepsis Patients with Early Critical Care...

Assessment of Outcomes in Septic Shock and Severe

Sepsis Patients with Early Critical Care Intervention

A Case Comparison Study

Kenmore Mercy Hospital, Buffalo, NY

Matthew Missert DO

Gopichand Pendurti MBBS

Thomas Brewer DO

Background & Rationale

Severe sepsis and septic shock are characterized by a Severe sepsis and septic shock are characterized by a systemic inflammatory state secondary to an infectious systemic inflammatory state secondary to an infectious cause with evidence of end-organ damage or hemodynamic cause with evidence of end-organ damage or hemodynamic instabilityinstability

In the United States there are an estimated In the United States there are an estimated 215,000215,000 deaths deaths annually as a result of severe sepsis and septic shockannually as a result of severe sepsis and septic shock

In the past, despite heroic measures septic shock and severe In the past, despite heroic measures septic shock and severe sepsis have carried a staggering mortality rate of sepsis have carried a staggering mortality rate of 40 to 50 40 to 50 percentpercent

Surviving Sepsis Campaign: http://www.survivingsepsis.org. 2012.


Shapiro N, Howell MD, Talmor D. Implementation and Outcomes of the Multiple Urgent Sepsis Therapies (MUST) Protocol.

Critical Care Medicine. 2006. 34(4), 1025-32.

Newer methods of treatment such as Newer methods of treatment such as those described by Rivers et. al. (Early those described by Rivers et. al. (Early Goal-directed Therapy) have Goal-directed Therapy) have demonstrated a 28-day reduction in demonstrated a 28-day reduction in mortality from mortality from 49.2 to 33.3 percent

Comparable results have been observed Comparable results have been observed with similar protocols placing emphasis on with similar protocols placing emphasis on urgency and appropriateness of treatment urgency and appropriateness of treatment


Rivers E, Nguyen B, Havstad S, et al. Rivers E, Nguyen B, Havstad S, et al. Early Goal-directed Therapy in the Treatment of Severe Sepsis Early Goal-directed Therapy in the Treatment of Severe Sepsis and Septic Shock. and Septic Shock. New England Journal of MedicineNew England Journal of Medicine. 2001; 345(19), 1368-1377.. 2001; 345(19), 1368-1377.


The Society of Critical Care Medicine in conjunction The Society of Critical Care Medicine in conjunction with the European Society of Intensive Care with the European Society of Intensive Care Medicine have established recommendations for Medicine have established recommendations for the management of severe sepsis and septic shockthe management of severe sepsis and septic shock

The The Surviving Sepsis CampaignSurviving Sepsis Campaign was established to was established to standardize the classification, diagnosis and standardize the classification, diagnosis and treatment protocols treatment protocols

The latest recommendations were released in The latest recommendations were released in 2008


Background & Rationale In summary, the In summary, the Surviving Sepsis CampaignSurviving Sepsis Campaign resuscitation bundle recommends the resuscitation bundle recommends the

following be completed within the first 6 hours of diagnosis:following be completed within the first 6 hours of diagnosis:

1.1. ICU admissionICU admission

2.2. Measurement of serum lactate within the first hourMeasurement of serum lactate within the first hour

3.3. Fluid resuscitation to achieve a CVP of ≥ 8 mmHg (≥ 12 mmHg in Fluid resuscitation to achieve a CVP of ≥ 8 mmHg (≥ 12 mmHg in mechanically ventilated patients) mechanically ventilated patients)

4.4. Maintenance of MAP ≥ 65 with the use of vasopressors if neededMaintenance of MAP ≥ 65 with the use of vasopressors if needed

5.5. Obtain blood cultures prior to the administration of antibiotics Obtain blood cultures prior to the administration of antibiotics

6.6. Administer broad spectrum antibiotics within the first 3 hours of ED Administer broad spectrum antibiotics within the first 3 hours of ED admission and within the first 1 hour of non-ED admissionadmission and within the first 1 hour of non-ED admission

7.7. Achieve a central venous oxygen saturation (ScvO2) > 70% OR a Achieve a central venous oxygen saturation (ScvO2) > 70% OR a mixed central venous oxygen saturation M(SvO2) > 65% mixed central venous oxygen saturation M(SvO2) > 65%


Background & Rationale On On January 1st, 2011 Kenmore Mercy Hospital Kenmore Mercy Hospital

implemented a modified sepsis bundle adapted from the implemented a modified sepsis bundle adapted from the University of Rochester Medical Center and Strong Memorial University of Rochester Medical Center and Strong Memorial Hospital in concordance with the Hospital in concordance with the Surviving Sepsis CampaignSurviving Sepsis Campaign

The modified sepsis bundle includes recommendations to The modified sepsis bundle includes recommendations to have the ICU team notified and involved in patient care as have the ICU team notified and involved in patient care as soon as a patient with severe sepsis or septic shock has soon as a patient with severe sepsis or septic shock has been identified in the emergency department been identified in the emergency department

It was postulated that there would be an improvement in It was postulated that there would be an improvement in morbidity and length of stay in this select patient population morbidity and length of stay in this select patient population at Kenmore Mercy Hospital after the implementation of 24-at Kenmore Mercy Hospital after the implementation of 24-hour critical care coverage and the use of the modified hour critical care coverage and the use of the modified sepsis bundle sepsis bundle

Design

A case-comparison retrospective analysisA case-comparison retrospective analysis

Comparison of patients admitted with a Comparison of patients admitted with a diagnosis of severe sepsis and/or septic diagnosis of severe sepsis and/or septic shock prior to and following the shock prior to and following the implementation of the protocol with 24 implementation of the protocol with 24 in-house critical care coveragein-house critical care coverage

Institutional review board approvalInstitutional review board approval

Design Inclusion criteriaInclusion criteria

– The fulfillment of SIRS (systemic inflammatory The fulfillment of SIRS (systemic inflammatory response syndrome), ANDresponse syndrome), AND

– Identifiable source of infection, ANDIdentifiable source of infection, AND– A systolic blood pressure no greater than 90 A systolic blood pressure no greater than 90

mmHg on arrival or after a crystalloid-fluid mmHg on arrival or after a crystalloid-fluid challenge, ORchallenge, OR

– Blood lactate concentration ≥ 19.8 mg/dL (4 Blood lactate concentration ≥ 19.8 mg/dL (4 mmol/L), ORmmol/L), OR

– Evidence of acute end-organ dysfunctionEvidence of acute end-organ dysfunction


Design Exclusion criteria Exclusion criteria

– age < 18 yearsage < 18 years– pregnancypregnancy– acute cerebral vascular accident (as a primary diagnosis)acute cerebral vascular accident (as a primary diagnosis)– acute coronary syndrome (as a primary diagnosis)acute coronary syndrome (as a primary diagnosis)– status asthmaticusstatus asthmaticus– cardiac dysrhythmia (as a primary diagnosis)cardiac dysrhythmia (as a primary diagnosis)– contraindication to central venous catheterizationcontraindication to central venous catheterization– active gastrointestinal hemorrhage (as a primary diagnosis)active gastrointestinal hemorrhage (as a primary diagnosis)– seizure on arrivalseizure on arrival– drug overdosedrug overdose– Do Not Resuscitate (DNR) order on arrival or within the first 72 Do Not Resuscitate (DNR) order on arrival or within the first 72

hours of admissionhours of admission


Design

Methods

Independent sample t-test analysisIndependent sample t-test analysis

Utilizing IBM Statistical Package for the Utilizing IBM Statistical Package for the Social Sciences (SPSS) softwareSocial Sciences (SPSS) software

Help from a statistically inclined Help from a statistically inclined colleague! colleague!

Outcome Measures

PrimaryPrimary– Absolute APACHE-II at 72 hoursAbsolute APACHE-II at 72 hours– Net reduction in APACHE-II at 72 hoursNet reduction in APACHE-II at 72 hours

SecondarySecondary– Hospital Length of Stay (days)Hospital Length of Stay (days)– ICU Length of Stay (days)ICU Length of Stay (days)– Emergency Department Length of Stay (hours)Emergency Department Length of Stay (hours)– Volume infused in the first 6 and 12 hoursVolume infused in the first 6 and 12 hours– Volume infused over the first 24 hoursVolume infused over the first 24 hours– MAP at 24 hoursMAP at 24 hours

APACHE-II ScoreAPACHE-II Score

Knaus WA, Draper EA, Wagner DP, Zimmerman JE. 1985. "APACHE II: a severity of disease classification Knaus WA, Draper EA, Wagner DP, Zimmerman JE. 1985. "APACHE II: a severity of disease classification system". system". Critical Care MedicineCritical Care Medicine 13 (10): 818–29. 13 (10): 818–29.

Results Without Protocol (N=95) With Protocol (N=53)

Age (years) 68.2 65.1

Weight on Arrival (kg) 78.4 85.6

Temperature on Arrival (˚C) 37.6 37.9

Heart Rate on Arrival (bpm) 106 106

24 Hour Input (liters) 6.05 8.42

24 Hour Ouput (liters) 2.11 2.34

MAP at 24 Hours 82 84.7

Percentage Receiving Central Line 49.4% 98.1%

*Mortality 25.3% (24/95) 20.7% (11/53)

*Underpowered to detect mortality

Results

Without Protocol (N=95)

With Protocol (N=53) p Value

APACHE-II at Arrival 17.5 21.5 <0.00001

Absolute APACHE-II at 72 Hours 15.7 14.9 0.419

Net Reduction in APACHE at 72 Hours

1.8 6.5 <0.00001

ED Length of Stay (Hours) 4.51 3.51 0.002

ICU Length of Stay (Days) 7.2 6.1 0.296

Hospital Length of Stay (Days) 13.6 10.7 0.046

Input in first 6 Hours (liters) 1.62 2.23 0.002

Input in first 12 Hours (liters) 3.13 5.15 <0.00001

Results


With Protocol (N=53) p Value

APACHE-II at Arrival 17.5 21.5 <0.00001

Absolute APACHE-II at 72 Hours 15.7 14.9 0.419

Net Reduction in APACHE at 72 Hours

1.8 6.5 <0.00001

ED Length of Stay (Hours) 4.51 3.51 0.002

ICU Length of Stay (Days) 7.2 6.1 0.296

Hospital Length of Stay (Days) 13.6 10.7 0.046

Input in First 6 Hours (liters) 1.62 2.23 0.002

Input in First 12 Hours (liters) 3.13 5.15 <0.00001

Results

1.8

6.5

0 1 2 3 4 5 6 7

APACHE-II Point Reduction


With Protcol (N=53)

Comparison in the Net Reduction of the APACHE-II Score at 72 Hours (p < 0.00001)

Results

4.513.51

0

1

2

3

4

5

Hours

Without Protocol (N=95) With Protcol (N=53)

Comparison in ED Length of Stay (p = 0.002)

Results

13.6

10.7

0

2

4

6

8

10

12

14

Hospital Days

Without Protocol (N=95) With Protcol (N=53)

Comparison in Hospital Length of Stay (p = 0.046)

Results Mean p Value

Age (Years)

Mortality (N=35) 76.4<0.001

No Mortality (N=113) 63.4

APACHE-II at 72

Mortality (N=35) 20.4<0.001


ED Length of Stay (Hours)

Mortality (N=35) 4.20.98


ICU Length of Stay (Days)



Hospital Length of Stay (Days)



Time (Hours) 0 6 12 18 24

Temperature ˚C

No Protocol (N=95) 37.5 37.3 37.5 37.5 37.5

Protocol (N=53) 37.9 37.4 37.6 37.7 37.5

Heart Rate (bpm)

No Protocol (N=95) 106 98 97 94 95

Protocol (N=53) 106 96 93 91 93

Input (liters)

No Protocol (N=95) 0.00 1.67 3.13 4.70 6.05

Protocol (N=53) 0.00 2.23 5.15 6.96 8.42

Output (liters)

No Protocol (N=95) 0.00 0.42 1.01 1.56 2.10

Protocol (N=53) 0.00 0.36 0.96 1.60 2.34

MAP

No Protocol (N=95) 79.0 76.9 76.0 76.4 78.2

Protocol (N=53) 75.0 73.6 75.6 74.1 78.8

Conclusions

The patients in the protocol arm had a The patients in the protocol arm had a significantly higher APACHE-II on arrival significantly higher APACHE-II on arrival (21.5 vs 17.5, p<0.00001)

There was a significant difference in the There was a significant difference in the net reduction in the APACHE-II score at net reduction in the APACHE-II score at 72 hours in the protocol arm 72 hours in the protocol arm (6.5 vs 1.8, p<0.00001) but no significant but no significant difference in the absolute APACHE-II difference in the absolute APACHE-II score at 72 hours score at 72 hours (14.9 vs 15.7, (14.9 vs 15.7, p=0.419)p=0.419)

Conclusions

The use of a sepsis bundle and protocol The use of a sepsis bundle and protocol significantly reduced the emergency department significantly reduced the emergency department length of stay by length of stay by 60 minutes (p=0.002)60 minutes (p=0.002)

The use of a sepsis bundle and protocol The use of a sepsis bundle and protocol significantly reduced the hospital length of stay by significantly reduced the hospital length of stay by 2.9 days (p=0.046)2.9 days (p=0.046)

The fluid input for the first 6 & 12 hours was The fluid input for the first 6 & 12 hours was significantly greater in the protocol vs the no significantly greater in the protocol vs the no protocol arms protocol arms (p=0.002 & p<0.00001, (p=0.002 & p<0.00001, respectivley)respectivley)

Discussion and Considerations

•19 of the 78 charts identified (24 percent) after the implementation of the sepsis bundle failed to follow the protocol

•These are missed opportunities to improve the patient’s APACHE-II and significantly reduce their ED & Hospital lengths of stay


The data included out layers in both arms that The data included out layers in both arms that may have actually skewed the results in favor may have actually skewed the results in favor non-significancenon-significance

However, these were still included in the However, these were still included in the analysis in order to preserve the integrity of the analysis in order to preserve the integrity of the datadata

Despite the out layers, hospital and emergency Despite the out layers, hospital and emergency department length of stay were still found to be department length of stay were still found to be significantly reducedsignificantly reduced


Underpowered to detect mortality between the Underpowered to detect mortality between the two armstwo arms

Analysis of the entire population reflects what we Analysis of the entire population reflects what we already know:already know:– The higher the APACHE-II, the greater the mortality The higher the APACHE-II, the greater the mortality (20.4 vs.

13.8, p<0.001)– The older the patient, the greater the mortality The older the patient, the greater the mortality (76.4 vs 63.4, (76.4 vs 63.4,

p<0.001)p<0.001)

APACHE-II has only been validated as a predictor APACHE-II has only been validated as a predictor of mortality at admission and not as a dynamic of mortality at admission and not as a dynamic predictor of mortality. However, APACHE-II is predictor of mortality. However, APACHE-II is routinely used in the literature as a severity of routinely used in the literature as a severity of illness index in a dynamic fashion (see Rivers et illness index in a dynamic fashion (see Rivers et al)al)


Statistical considerationsStatistical considerations– p-Value of < 0.00001 is not always a good p-Value of < 0.00001 is not always a good

thingthing

– As in the case of the net reduction of the As in the case of the net reduction of the APACHE-II and APACHE-II at arrival having APACHE-II and APACHE-II at arrival having p<0.00001p<0.00001

– Can either mean the data is truly highly Can either mean the data is truly highly significant or there is the presence of a Type-I significant or there is the presence of a Type-I (alpha) error(alpha) error e.g. Falsely rejecting the null hypothesise.g. Falsely rejecting the null hypothesis


Can the principles learned from early Can the principles learned from early goal directed therapy be executed in a goal directed therapy be executed in a small community based hospital and small community based hospital and have meaningful outcomes?have meaningful outcomes?

–YES !!!!!!!!!!!!!!!!YES !!!!!!!!!!!!!!!!

QuestionsQuestions

References1.1. Schmidt GA, Mandel J, Parsons, PE, et al. Management of Severe Sepsis and Septic Schmidt GA, Mandel J, Parsons, PE, et al. Management of Severe Sepsis and Septic

Shock in Adults. UpToDate®. February 3, 2010.Shock in Adults. UpToDate®. February 3, 2010.

2.2. Shapiro N, Howell MD, Talmor D. Implementation and Outcomes of the Multiple Urgent Shapiro N, Howell MD, Talmor D. Implementation and Outcomes of the Multiple Urgent Sepsis Therapies (MUST) Protocol. Sepsis Therapies (MUST) Protocol. Critical Care MedicineCritical Care Medicine. 2006. 34(4), 1025-32.. 2006. 34(4), 1025-32.

3.3. Dellinger RP, Levy, MM, Carlet JM, et. al. Surviving Sepsis Campaign: International Dellinger RP, Levy, MM, Carlet JM, et. al. Surviving Sepsis Campaign: International Guidelines for Management of Severe Sepsis and Septic Shock: 2008. Guidelines for Management of Severe Sepsis and Septic Shock: 2008. Critical Care Critical Care MedicineMedicine. 2008.. 2008.

4.4. The Surviving Sepsis Campaign: The Surviving Sepsis Campaign: http://www.survivingsepsis.orghttp://www.survivingsepsis.org. 2012. . 2012.

5.5. Rivers E, Nguyen B, Havstad S, et al. Rivers E, Nguyen B, Havstad S, et al. Early Goal-directed Therapy in the Treatment of Early Goal-directed Therapy in the Treatment of Severe Sepsis and Septic Shock. Severe Sepsis and Septic Shock. New England Journal of MedicineNew England Journal of Medicine. 2001; 345(19), . 2001; 345(19), 1368-1377.1368-1377.

6.6. Knaus WA, Draper EA, Wagner DP, Zimmerman JE. 1985. "APACHE II: a severity of Knaus WA, Draper EA, Wagner DP, Zimmerman JE. 1985. "APACHE II: a severity of disease classification system". disease classification system". Critical Care MedicineCritical Care Medicine 13 (10): 818–29. 13 (10): 818–29.

7.7. Bryan-Brown CW, Dracup K. Procrastination is the Thief of Time: Surviving Guidelines. Bryan-Brown CW, Dracup K. Procrastination is the Thief of Time: Surviving Guidelines. American Journal of Critical Care.American Journal of Critical Care. 2004; 14(4), 287-289. 2004; 14(4), 287-289.

8.8. Talmore D, Greenberg D, Howell M et al. The Cost and Cost-effectiveness of an Talmore D, Greenberg D, Howell M et al. The Cost and Cost-effectiveness of an Integrated Sepsis Treatment Protocol. Integrated Sepsis Treatment Protocol. Critical Care MedicineCritical Care Medicine. 2008; 36(4), 1168-1174. . 2008; 36(4), 1168-1174.

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