sepsis april 7, 2014 david griffen, md, phd southern illinois university school of medicine division...

Sepsis

April 7, 2014

David Griffen, MD, PhDSouthern Illinois University School of Medicine

Division of Emergency Medicine

“Hectic fever at its inception is difficult to recognize but easy to treat. Left untended, it becomes easy to recognize but difficult to treat.”

72 Year old admitted with acute exacerbation of COPD

• PMH– COPD/emphysema.– Pulmonary fibrosis.– Recurrent pneumonias– Rheumatoid arthritis on chronic steroids.– History of DVT and PE– Diabetes mellitus type 2, most likely steroid-

induced.– Hypertension.– Paroxysmal atrial fibrillation.– Peripheral vascular disease.

Called to room for generalized body aches

• Patient looks pale and uncomfortable • Temperature 38.5 Deg C• Pulse Rate 93• Respiratory Rate 20 br/min • Systolic Blood Pressure 81 mmHg • Diastolic Blood Pressure 42 mmHg • O2 Sat Resting 88 %

What does this patient have?

What do you do next?

What does this patient need?

Topics We Will Cover

1. Definitions2. Scope3. Surviving Sepsis Campaign4. Early identification and Lactate5. ED treatment priorities6. The controversy7. PROCESS

Definitions

Definitions

• Systemic inflammatory response (SIRS)• Sepsis• Severe sepsis• Sepsis induced hypotension• Septic shock

Systemic Inflammatory Response Syndrome = SIRS

• Systemic inflammatory response syndrome is defined as the presence of 2 or more of the following: (1) temperature > 38°C (100.4°F) or < 36°C (96.8°F); (2) pulse > than 90 beats/min; (3) Respiratory rate > than 20 breaths/min

(or PaCO2 < 32 torr) (4) WBC count >12,000/mm3 or < 4,000/mm3, or >

10% immature band forms.

Does our patient have SIRS?

• Temperature 38.5 Deg C• Pulse Rate 93• Respiratory Rate 20 br/min • Systolic Blood Pressure 81 mmHg • Diastolic Blood Pressure 42 mmHg • O2 Sat Resting 88 %

One Definition of Sepsis

Sepsis = SIRS + Infection

Does our patient have Sepsis?


Problem with SIRS

• Not specific• Does not appear to have any real prognostic

value

Shapiro, N., M. D. Howell, et al. (2006). "The association of sepsis syndrome and organ dysfunction with mortality in emergency department patients with suspected infection." Ann Emerg Med 48(5): 583-90, 590 e1.

SIRS

• Silly• Inappropriate• Renaming• Syndrome

Why Use SIRS In Definition of Sepsis?

• Relatively simple• Easy to teach• Focuses staff on sepsis• Other definitions too complex

And another definition of sepsis …..

Sepsis = SIRS + Infection

• Relatively simple• Easy to teach• Focuses staff on sepsis• Other definitions too complex

Severe Sepsis• Severe sepsis is defined as the presence of sepsis

and 1 or more organ dysfunction. Organ dysfunction can be defined as:– acute lung injury– coagulation abnormalities– thrombocytopenia– altered mental status– renal, liver, or cardiac failure– hypoperfusion with lactic acidosis.

Mortality up to 30-50 %

Does our patient have Severe Sepsis?


Sepsis-Induced Hypotension

Sepsis with:• SBP < 90 mm Hg or • Mean arterial pressure < 70 mm Hg

(or SBP decrease > 40 mm Hg or 2 SD below normal for age)

Does our patient have Sepsis-Induced Hypotension?


Septic Shock

• Septic shock is defined as the presence of sepsis and refractory hypotension unresponsive to a crystalloid fluid challenge of at least 30 mL/kg)

Mortality 50-60%

Does our patient have Septic Shock?


Definitions

• SIRS• Sepsis• Severe sepsis• Sepsis induced hypotension• Septic shock

SIRS

SEPSIS

SEVERE SEPSIS

SEPTIC SHOCK

Bacteremia ≠ Sepsis• Bacteremia– Presence of viable bacteria in the blood– Found only in about 50% of cases of severe

sepsis and septic shock– 20% to 30% of patients with severe sepsis or

septic shock will have no microbial cause identified from any source.

Sorting… by severity of illness (instead of site of infection or etiology)

SIRS

SEPSIS

SEVERE SEPSIS

SEPTIC SHOCK

Sort patients….

… by severity of illness instead of site of infection or etiology•The severity of illness determines the type and urgency of treatment.•Site of infection and presumed etiology determines antibiotic choice.

Sites of Infection in Sepsis

• Lung- 45%• Abdomen- 17%• Urinary tract- 10%• Undetermined- 20-30%

N Engl J Med 340(3):207

Sites of Infection for Sepsis Patient

• Lung (35%)• Abdomen (21%)• Urinary tract (13%) (However this is the most

common site for patients older than 65 years old)• Skin and soft tissue (7%)• Other site (8%),• Unknown primary site (16%)

Compiled from 16 studies between 1963 and 1998 that included 8,667 patients)

For the rest of the talk will be addressing severe sepsis and

septic shock

• Scope• Incidence • Mortality• Surviving Sepsis Campaign

Bugs

• Bacteria– Gram negative (used to cause majority)– Gram positive (now in the majority)

• Virus• Fungus

Scope

• 750,000 US patients with severe sepsis• 29% overall hospital mortality rate• 210,000 deaths per year in US• Increasing by at least 1.5% a year• $16.2 to $24 billion a year• About 50% admitted through ED

SIRS

SEPSIS

SEVERE SEPSIS

SEPTIC SHOCK

LACTATE ≥ 4

Early Goal-Directed Therapy in the Treatment of Severe Sepsis and Septic Shock

NEJM 2001• Randomized patients (n=263) with septic

shock, or severe sepsis with lactate ≥ 4, to receive standard therapy (n=133) or EGDT (n=130)

• In-hospital mortality was 30.5 percent for EGDT group and 46.5 percent in the group assigned to standard therapy (p=0.009)

• Absolute mortality reduction of 16 percent

The Importance of Early Goal-DirectedTherapy for Sepsis Induced Hypoperfusion

Adapted from Table 3, page 1374, with permission from Rivers E, Nguyen B, Havstad S, et al. Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med 2001; 345:1368-1377

In-hospital mortality

(all patients)

0

10

20

30

40

50

60 Standard therapyEGDT

28-day mortality

60-day mortality

NNT to prevent 1 event (death) = 6-8

Mort

ality

(%

)

Surviving Sepsis CampaignSponsoring Organizations

• American Association of Critical-Care Nurses

• American College of Chest Physicians

• American College of Emergency Physicians

• American Thoracic Society• Australian and New

Zealand Intensive Care Society

• Episepsis

• European Society of Clinical Microbiology and Infectious Diseases

• European Society of Intensive Care Medicine

• European Respiratory Society

• German Sepsis Society• Indian Society of Critical

Care Medicine• International Sepsis Forum• Society of Critical Care

Medicine• Surgical Infection Society

Bundles

What is a Bundle?• Specifically selected

care elements from evidence based guidelines

• Implemented together provide improved outcomes compared to individual elements alone

1. Serum Lactate Measured

Why lactate?

• Produced in anaerobic metabolism• Marker for decreased tissue perfusion (shock)• Can be available in minutes via POC testing

Causes of Elevated Lactate

ARTERIAL VERSUS VENOUS LACTATE

2. Blood cultures obtained prior to antibiotics

3. Broad spectrum antibiotics within 3 hrs of ED arrival and within 1 hr of recognition of severe sepsis/septic shock

Timing of Antibiotics in Septic Shock

• 2,731 adult patients with septic shock• Antimicrobial administration within the first

hour of hypotension was associated with a survival rate of 79.9%.

• Each hour of delay in antimicrobial administration over the ensuing 6 hrs was associated with an average decrease in survival of 7.6%.

Kumar, A., D. Roberts, et al. (2006). "Duration of hypotension before initiation of effective antimicrobial therapy is the critical determinant of survival in human septic shock." Crit Care Med 34(6): 1589-96.

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21-78.3

21.8

121.8

221.8

321.8

421.8

521.8

UCL 440.3

CL 218.1

LCL -4.1

Door to Antibiotics Started

Patients

Door

to A

ntibi

otics

Sta

rted

in M

inut

es

4. In the event of hypotension and/or lactate > 4.0 mmol/l:

- Deliver an initial minimum of 30 ml/kg crystalloid bolus- Vasopressors for hypotension not responding to initial fluid resuscitation to maintain MAP > 65 mm Hg

Which vasopressor?

Figure B, page 948, reproduced with permission from Dellinger RP. Cardiovascular management of septic shock. Crit Care Med 2003;31:946-955.

Search for a source and control it ASAP

• Drain any infected fluid• Debride infected tissue• Remove infected devices

Marshall JC - Crit Care Med - 01-NOV-2004; 32(11 Suppl): S513-26

The Controversy

The Controversy……

“But now some doctors are questioning the rigor of the research behind it, which was done at a single hospital. Adding to the concerns …..one of the groups that later endorsed the treatment had financial backing from the maker of the device.”

“"One concern I have is that this hypothesis has been accepted almost without debate by so many people," says Mitchell Fink, a professor of critical-care medicine at the University of Pittsburgh Medical Center.

“All this has angered the doctor who pioneered the aggressive therapy, Emanuel P. Rivers….Dr. Rivers has called his critics in Pittsburgh "the Pittsburgh pirates.“”

Does it Work?

Rivers and Ahrens, Crit Care Clin, 2008,S1-47

20% Absolute Risk Reduction

Meta-analysis On EGDT

• Meta analysis• 9 studies were included• 1001 patients• “CONCLUSION: This meta-analysis found that

applying an early quantitative resuscitation strategy to patients with sepsis imparts a significant reduction in mortality.”

Jones, A. E., M. D. Brown, et al. (2008). "The effect of a quantitative resuscitation strategy on mortality in patients with sepsis: a meta-analysis." Crit Care Med 36(10): 2734-9.

ProCESS (Protocolized Care for Early Septic Shock)

• NIH grant of $8.4 million over 5 years• Plan to enroll 1,935 patients at 24 institutions• Directed by investigators at UPMC, Pittsburgh• Three arms– “standard” therapy for severe sepsis– EGDT– Protocolized standard care (portion of EGDT

including fluid boluses, vasopressors, PRBC)

PROCESS TRIAL

Everyone Should Implement:

• Early recognition• Lactate• Aggressive fluid resuscitation• BP support with fluid and pressors• Early antibiotics• Protocols with ICU Cooperation

The perfect is the enemy of the good.”- Voltaire

Some Specific Operational Points to Stress

• Blood cultures = lactate• Lactate should be taken from the first blood drawn• Bolus is not given on a pump• VS should be repeated after any IV bolus• Need accurate I and Os• Rectal temperatures are necessary if:

– Patient is tachypneic– Oral temperature is less than 96.8 F– You have any thought that oral temperature may not be accurate. – Elderly persons with vague complaints and a normal or low oral

temperature

Take Home Points

• Need to recognize severely septic patients early

• Focus on severity of illness and not source of infection

• Get lactate early• Aggressive fluid treatment• Early broad spectrum antibiotics

Make sure you…

• Get your sepsis protocol and know what is in it.

• Get your pneumonia protocol and know what is in it.

Topics We Will Cover

1. Definitions2. Scope3. Surviving Sepsis Campaign4. Early identification and Lactate5. ED treatment priorities6. The controversy7. PROCESS

THANK YOU

QUESTIONS?

References• Berkman M, Ufberg J, et al. Anion gap as a screening tool for elevated lactate in

patients with an increased risk of developing sepsis in the emergency department. J Emerg Med In Press, Corrected Proof, Available online 23 Sept 2008.

• Butler J. The Surviving Sepsis Campaign (SSC) and the emergency department. J Emerg Med 2008; 25(1):2-3.

• Carboy DJ, Rubenfeld GD. Barriers to implementing protocol-based sepsis resuscitation in the emergency department - results of a national survey. Crit Care Med 2007; 35(11):2525-32.

• Chalfin DB, Trzeciak S, Likourezos A, Baumann BM, Dellinger RP, DELAYED study group. Impact of delayed transfer of critically ill patients from the emergency department to the intensive care unit. Crit Care Med 2007; 35:1477-83.

• Dellinger RP, Carlet JM, et al. Surviving Sepsis Campaign guidelines for management of severe sepsis and septic shock. Crit Care Med 2004; 32(3):858-73.

• Dellinger RP, Levy MM, et al. Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock: 2008. Intensive Care Med 2008; 34(1):17-60.

References page 2• Dellinger RP, Levy MM, Carlet JM, et. Al. Surviving Sepsis Campaign:

International guidelines for management of severe sepsis and septic shock: 2008 [published correction appears in Crit Care Med 2008; 36:1394-1396]. Crit Care Med 2008; 36:296-327.

• Djurkovic S, et al. Implementation of sepsis guidelines in the United States: A comparison between critical care and emergency department physicians. Crit Care Med 2007; 35(12 Suppl.): A274 35(12 Suppl.): A274.

• Go F, Melody T, Daniels DF, et al. The impact of compliance with 6-hour and 24-hour sepsis bundles on hospital mortality in patients with severe sepsis: a prospective observational study.

• Jones AE, Shapiro NI, Roshon M. Implementing early goal-directed therapy in the emergency setting: The challenges and experiences of translating research innovations into clinical reality in academic and community settings. Acad Emerg Med 2007 Nov; 14(11):1072-8.

• Jones AE, Brown MD, et al. The effect of a quantitative resuscitation strategy on mortality in patients with sepsis: a meta-analysis. Crit Care Med 2008; 36(10):2734-9.

References page 3• 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; 34:1589-1596.

• Line G, et al. Clinical and financial outcomes associated with a sepsis initiative. Crit Care Med 2007; 35(12 Suppl.): A258 .

• Mooney R, and Henry Ford Hospital Sepsis Collaborative Group. An institutional sepsis collaborative: The impact of a continuous quality improvement process. Crit Care Med 2007; 35(12 Suppl.): A259 .

• Nguyen HB, Oh J, et al. Standardization of Severe Sepsis Management: A Survey of Methodologies in Academic and Community Settings. J Emerg Med 2008, In Press, Corrected Proof, Available online 23 July 2008.

• Nguyen HB, Corbett SW, Steele R, et al. Implementation of a bundle of quality indicators for the early management of severe sepsis and septic shock is associated with decreased mortality. Crit Care Med 2007; 35:1105-1112.

• Osborn TM, Nguyen HB, et al. Emergency medicine and the surviving sepsis campaign: an international approach to managing severe sepsis and septic shock. Ann Emerg Med 2005; 46(3):228-31.

References page 4• Otero RM, Nguyen HB, et al. Early goal-directed therapy in severe sepsis and

septic shock revisited: concepts, controversies, and contemporary findings. Chest 2006; 130(5):1579-95.

• Patel GP, Elpern EH, Balk RA. A campaign worth joining: improving outcome in severe sepsis and septic shock using the Surviving Sepsis Campaign guidelines. South Med J 2007; 100:557-8.

• Rivers E, Nguyen B, et al. Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med 2001; 345(19):1368-77.

• Shapiro NI, Howell MD, et al. Serum lactate as a predictor of mortality in emergency department patients with infection. Ann Emerg Med 2005; 45(5):524-8.

• Shapiro N, Howell MD, et al. The association of sepsis syndrome and organ dysfunction with mortality in emergency department patients with suspected infection. Ann Emerg Med 2006; 48(5):583-90, 590 e1.

• Sivayoham N. Management of severe sepsis and septic shock in the emergency department: a survey of current practice in emergency departments in England. Emerg Med J 2007; 24:422.

References page 5• Sprung CL, Annane D, Keh D, et al., CORTICUS Study Group. Hydrocortisone

therapy for patients with septic shock. N Engl J Med. 2008; 358(2):111-24. • Trzeciak S, Dellinger RP, Abate NL, et al. Translating research to clinical practice:

a 1-year experience with implementing early goal-directed therapy for septic shock in the emergency department. Chest 2006; 129:225-232.

• Varpula M, Karlsson S, Parviainen I, Ruokonen E, Pettilä V, Finnsepsis Study Group. Community-acquired septic shock: early management and outcome in a nationwide study in Finland. Acta Anaesthesiol Scand. 2007; 51(10):1320-6.

• Vincent JL and Korkut HA. Defining sepsis. Clin Chest Med 2008; 29(4):585-90, vii.

Nguyen, H. B., J. Oh, et al. (2008). "Standardization of Severe Sepsis Management: A Survey of Methodologies in Academic and Community Settings." J Emerg Med.

Conclusions: Implementation of a sepsis management protocol incorporating evidence-based therapies can be accomplished in both academic and community hospitals, with minimal additional staffing. The presence of a protocol champion and education program is crucial to success, and may result in improved patient outcome.

Chalfin DB, Trzeciak S, Likourezos A, Baumann BM, Dellinger RP, DELAYED study group. Impact of delayed transfer of critically ill patients from the emergency department to the intensive care unit. Crit Care Med 2007; 35:1477-83

A study of emergency department patients analyzed those that were held 6 hours or longer in the ED after ICU admission versus those that were not. Mortality was significantly greater in those held 6 hours or longer, with severe sepsis being a particularly good example of a patient group exhibiting this finding. Although not proven cause and effect, it does clearly establish the association.

Nguyen HB, Corbett SW, Steele R, et al. Implementation of a bundle of quality indicators for the early management of severe sepsis and septic shock is associated with decreased mortality. Crit Care Med 2007; 35:1105-1112

Implementation of a severe sepsis bundle using quality improvement feedback to modify physician behavior in the emergency department setting is feasible and associated with decreased inhospital mortality.Trzeciak S, Dellinger RP, Abate NL, et al. Translating research to clinical practice: a 1-year experience with implementing early goal-directed therapy for septic shock in the emergency department. Chest. 2006; 129:225 232.

This study demonstrates the successful implementation of the Rivers early-goal directed therapy protocol in a real life environment as part of a quality improvement initiative.

Varpula M, Karlsson S, Parviainen I, Ruokonen E, Pettilä V, Finnsepsis Study Group. Community-acquired septic shock: early management and outcome in a nationwide study in Finland. Acta Anaesthesiol Scand. 2007; 51(10):1320-6.

This is the first publication of a nationwide study that evaluated the early treatment strategy in community-acquired septic shock in Finnish hospitals using the Surviving Sepsis Campaign Guidelines Sepsis Bundles. The delayed initiation of antibiotics was associated with the greatest impact on mortality.

Jones AE, Shapiro NI, Roshon M. Implementing early goal-directed therapy in the emergency setting: The challenges and experiences of translating research innovations into clinical reality in academic and community settings. Acad Emerg Med. 2007

Nov;14(11):1072-8. The feasibility with which institutions may translate early goal directed resuscitation (EGDR) from a research protocol into routine clinical care, among settings with varying resources, staff, and training, is largely unknown. The authors reported their experience during EGDR including protocol development/deployment, and preimplementation/post-implementation issues, at three institutions with different emergency department, intensive care unit, and hospital organization schemes.

Finfer, S., R. Bellomo, et al. (2004). "A comparison of albumin and saline for fluid resuscitation in the intensive care unit." N Engl J Med 350(22): 2247-56.

A multicenter, randomized, double-blind trial to compare the effect of fluid resuscitation with albumin or saline on mortality in a heterogeneous population of patients in the CONCLUSIONS: In patients in the ICU, use of either 4 percent albumin or normal saline for fluid resuscitation results in similar outcomes at 28 days.Nguyen HB, Corbett SW, Steele R, et al. Implementation of a bundle of quality indicators for the early management of severe sepsis and septic shock is associated with decreased mortality. Crit Care Med 2007; 35:1105-1112

Implementation of a severe sepsis bundle using quality improvement feedback to modify physician behavior in the emergency department setting is feasible and associated with decreased inhospital mortality.

Mooney R, and Henry Ford Hospital Sepsis Collaborative Group. An institutional sepsiscollaborative: The impact of a continuous quality improvement process. Crit Care Med. 2007; 35(12 Suppl.): A259

652 patients with severe sepsis and septic shock were evaluated. Significant correlation between compliance to resuscitation bundle elements and mortality was found. The authors concluded that in spite of promising developments in therapy, compliance with bundle elements is likely the final path to improving outcome.Line G, et al. Clinical and financial outcomesassociated with a sepsis initiative. Crit Care Med. 2007; 35(12 Suppl.): A258

A multifaceted sepsis initiative that included a sepsis protocol, and focused education on early screening and the sepsis treatment bundle, improved clinical outcomes and substantially reduced cost of care (up to $6.9 million for the 15-month post-implementation period) in a tertiary care hospital with 157 ICU beds.

Carboy DJ, Rubenfeld GD. Barriers to implementing protocol-based sepsis resuscitation in the emergency department–results of a national survey. Crit Care Med. 2007; 35(11):2525-32.

Barriers to initiation and implementation of EGDT, and barriers that distinguish EGDT from other time-sensitive emergency practices (ie, intervention in myocardial infarction and cerebrovascular accident) were examined. The study demonstrated that nursing staffing to perform EGDT, monitoring central venous pressure in the ED, and identification of septic patients are the most important barriers to implementing an early goal-directed therapy resuscitation protocol for severe sepsis. Providing critical care in the ED and coordinating this care with an intensive care unit team will help for rapid identification and intervention of sepsis.

sepsis april 7, 2014 david griffen, md, phd southern illinois university school of medicine division...

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