AnnMarie Papa, DNP,RN,CEN,NE-BC,FAEN, FAAN Clinical Director, Emergency, Medical & Observation Nursing Hospital of the University of Pennsylvania

AnnMarie Papa, DNP,RN,CEN,NE-BC,FAEN, FAAN Clinical Director, Emergency, Medical & Observation Nursing Hospital of the University of Pennsylvania

Who Am I?

Except on few occasions, the patient appears to die from the body s response to infection rather than from [the infection itself.] Sir William Osler, 1904

Endothelial, mitorchondrial and cell membrane pump dysfunction Intracellular edema Leakage of intracellular contents into the extracellular space Inflammatory cascade

} A patient a minute presents to a US ED } 750,000 cases/yr of severe sepsis in USA } 215,000 deaths/yr directly related to sepsis } Tenth leading cause of death in USA } Rate of sepsis cases is increasing faster than the population } 37% of severe sepsis patients come through the ED Wang et al. Crit Care Med, 2007 Angus et al. Crit Care Med, 2001

} The Continuum SIRS Sepsis Severe Sepsis Septic Shock

} Systemic Inflammatory Response Syndrome Manifested by 2 or more of the following: Temperature > 38 C (100.4F) or < 36 C (96.8F) HR > 90 BPM RR > 20/min or PaCO PaCO2 < 32 mm Hg WBC 12,000 or >10 bands Systemic

The Continuum of Sepsis SIRS Sepsis Severe Sepsis Septic Shock Systemic Inflammatory Response Syndrome SIRS criteria Temp < 96.8 or > 100.4 F HR > 90 RR > 20 or PCO 2 < 32 WBC < 4 or > 12 or bands > 10% Bone et al. Chest 1992

The Continuum of Sepsis SIRS Sepsis Severe Sepsis Septic Shock Systemic Inflammatory Response to Infection Suspected or confirmed infection 2 or more SIRS criteria Bone et al. Chest 1992

The Continuum of Sepsis SIRS Sepsis Severe Sepsis Septic Shock Sepsis plus Organ Dysfunction Elevated Creatinine Elevated INR Altered Mental Status Elevated Lactate Hypotension that responds to fluid Levy et al. Crit Care Med; 2003

The Continuum of Sepsis SIRS Sepsis Severe SepsisSeptic Shock Cryptic Shock Normotensive Severe Sepsis and Hypotension Hypotension that does NOT respond to fluid (30 cc/kg bolus) Lactate > 4 Bone et al. Chest, 1992 Rivers et al. NEJM, 2001

} In 2004 Surviving Sepsis Campaign Adapted the original Rivers Protocol and other research Created practice guidelines. Outlined resuscitation and management bundles. Stated goal was 25% reduction in mortality. } Severe Sepsis Resuscitation Bundle. } Goal was to perform outlined tasks within six hours.

Rivers et al. NEJM, 2001 Algorithmic

} Resuscitation Bundle included: Measurement of Lactic Acid. Blood cultures prior to antibiotic administration. Appropriate broad spectrum antibiotics in 3 hours (ED arrival). IF hypotension IV fluid bolus (20ml\kg initial) IF continued hypotension or lactic acid > 4 Achieve MAP > 65 Achieve central venous pressure 8 mmhg or greater Achieve central venous oxygen sat. of 70%

Achieve MAP > 65 Continued fluid boluses. Adequate fluid resuscitation is a key component. Initiation of vasopressor agents. Norepinephrine Dopamine Norepinephrine appears to be the more common choice. Sepsi

} Norepinephrine Extensive a-adrenergic response. Moderate b-adrenergic response. Works mostly through vasoconstrictive actions. Does not change heart rate, cardiac output. 0.05 5 microgram\kg\minute (titrated to effect).

Achieve CVP 8 mmhg or greater Goal is 12 mmhg in intubated patients. Generally measured via an above the diaphragm central venous line. Subclavian Internal Jugular (preferred for US guided) Achieved through repeated fluid boluses (normal saline, lactated ringers). S

} Central Venous Pressure Pressure in Right Atrium Reflective of Preload Normal between 5 and 10 mmhg Can be measured through a standard triple lumen catheter

Achieve central venous O 2 Sat of 70% Can be drawn from same central line and run in a blood gas analyzer. (intermittent) Continual monitoring available from a specialized catheter. (PreSep, Edwards) If Hgb less than 10 mg\dl, transfuse PRBCs until you meet this goal. If Hgb already above 10 mg\dl, use dobutamine to achieve this goal.

} Dobutamine Inotrope Strong beta adrenergic response Start at 5 mcg\kg\minute Maximum of 20 mcg\kg\minute May increase hypotension so norepinephrine may be required to counteract this effect Goal is to increase cardiac output t

} Summarizing EGDT Achieve adequate fluid resuscitation. Vasopressors to keep MAP > 65 mmhg. Measure CVP and Central Venous Oxygen Saturation Additional fluids to achieve adequate CVP. CV oxygenation as a marker of adequate tissue perfusion Maximize other parameters first (especially CVP). If anemic transfuse. If not anemic consider an inotrope (dobutamine).

} Summarizing EGDT Continuing research is being done to fine tune and support this approach. Clearly being more aggressive is beneficial. Septic shock patients tended to be under-resuscitated coming out of ED. Better coordination between ED and ICU is critical.

60.0% 56.9% 50.0% 46.5% 49.0% 44.3% 40.0% 30.0% 20.0% 30.5% 33.3% Standard EGDT 10.0% 0.0% In House 28-Day 60-Day 15.7% at 28-days and 12.6% at 60-days. Rivers et al NEJM, 2001

Mortality 70 60 50 40 30 20 10 0 7.6% absolute increase in mortality per hour Time 0 1 hour 2 hours 3 hours 4 hours 5 hours 6 hours Time to Antibiotic Kumar et al. Critical Care Medicine. 2006

} To study the relationship between time to antibiotics and mortality in patients treated with EGDT in the ED } 261 patients } Average time to antibiotics: Triage to antibiotics: 119 minutes Qualification for EGDT to antibiotics: 42 minutes Gaieski et al Crit Care Med, 2010

} EGDT } 261 patients } Age 59 } 41% female Inpatient Mortality (%) } 31.3% Mortality } Median TTA 119 minutes 45 40 35 30 25 20 15 10 25.2 38.6 40.4 28.4 28.7 44.7 Goal Delayed 5 0 < 1 hour < 2 hour < 3 hour Antibiotic Timing Gaieski DF et al Crit Care Med 2010

Broad-Spectrum Antimicrobials: + Cefepime 1 gm IV (1) + Vancomycin 1 gm ( 70 kg) or 1.5 gm (> 70 kg) IV ± Amikacin 15 mg/kg or 7.5 mg/kg (CrCl < 20) IV (4) No PCN Allergy Yes Broad-Spectrum Antimicrobials: + Levofloxacin 750 mg IV + Vancomycin 1 gm ( 70 kg) or 1.5 gm (> 70 kg) IV ± Amikacin 15 mg/kg or 7.5 mg/kg (CrCl < 20) IV (4) Community Acquired Pneumonia: + Azithromycin 500mg IV (2) Anaerobic Source: + Metronidazole 500 mg IV (3) On TPN: + Fluconazole 400 mg IV Prolonged Neutropenia ± Steroids: + Caspofungin 70 mg IV ± Hydrocortisone 50-100 mg IV Gaieski et al, CCM, 2011

} Stabilize patient } Eradicate source of infection } Restore perfusion } Modulate body s inflammatory and anti-inflammatory responses } Cessation of ongoing lactate production

Mortality in Admitted Patients 50 46 Mortality, % 40 30 20 17 16 20 10 3 7 10 0 No SIRS SIRS 2 SIRS 3 SIRS 4 Sepsis Severe Sepsis Septic Shock RANGEL-FRAUSTO JAMA 1995

In Triage, early iden.fica.on of the sepsis pa.ent is vital: Who is at risk? What are the signs to look for?

A Bacterial infection is a major risk factor for sepsis Those with a poor immune system are at higher risk (Immunosuppressive therapy, Diabetes, Cancer, Alcohol Abuse, HIV/AIDS Two thirds of patients with Sepsis are older than 65 Sepsis is more common in men African Americans are more prone than any other race

} Those with suspected sources of infection Pneumonia UTI s Wounds

} Patients with CVP s, PICC s } Foleys } Ventilators } Always consider bounce backs

Utilize the SIRS Criteria (Sudden Inflammatory Response Syndrome): Temp > 100.4 F or < 96.8F HR > 90 BPM RR >20 breaths per minute WBC > 12,000 or < 4,000 (not usually known in triage)

Severe Sepsis Pathway Hospital of the University of Pennsylvania Emergency Department Yes CVP 8 No 1. At least 2 SIRS criteria HR>90 RR>20 T>100.4 or <96.8 WBC >12 or <4) 2. Suspected infection 3. Lactate >4 or SBP<90 (after 30cc/kg IVF bolus) Insert CVC in IJV or SCV Evaluate ScV02 Calculate Apache II score and notify SAR for MICU bed Yes Yes ScvO 2 70% Yes No MAP 65 baseline ScvO 2 70% Bolus 500 ml NS q15-20 Assess for pulmonary edema if>3l given No 1. Start/Titrate norepi or dopamine 2. Dexamethasone for refractory hypotension 3. Place arterial line if time permits Recheck Hgb by super gas Transfuse PRBC s until HgB 10 No Start/Titrate Dobutamine Yes ScvO 2 70% No CVP, MAP, ScvO2 goals achieved Re-evaluate to achieve goals

} Any person that is a concern for Sepsis ESI 2 } If hypotensive, increased urgency } Triage protocols if room not immediately available; Labs, X rays

Assess patient Important for baseline assessment possible changes in condition later Cardiac Monitor Oxygen Vital signs q 1 hour minimum EKG CXR Treat fever IV access 2 peripheral IV sites 18g or 20g for fluid resuscitation

Labs CBC, BMP, LFT s, CMP, PT/PTT, Type and Screen, VBG and Serum Lactate Blood Cultures Urine Urinalysis, Urine C&S Cultures if applicable Wounds, sputum, stool for c diff IV fluid bolus 1 to 2 liters/hour Anticipate Vasopressors Hypotension not responding to initial fluid resuscitation to maintain MAP > 65 mm Hg

10 Symptoms of Physiologic Instability Temperature change Increased pulse New or changing pain Changes in respiratory rate Decreased systolic and mean arterial pressure Change in LOC (lethargy or anxiety) Capillary refill greater than 3 seconds Urine output < 30 ml/hr. Changes in ScVO2 (measured via blood gas analysis) SaO2 < 90% (oxygen saturation-arterial)

Mentation Malaise, lethargy, restlessness Decreased LOC, stupor, coma Cutaneous Warm, flushed, dry Cold, clammy, pale, mottled skin Heart rate Tachycardia, bounding pulses Tachycardia, weak thready pulses Respiratory rate > 20/min Shallow and tachypneic Urine Decreased Decreased to anuric Acid-base values Respiratory alkalosis Metabolic and respiratory acidosis Body temperature Fever and chills Hypothermic and mottled

Per Pharmacy protocol -for patients with Sepsis or Septic Shock Administer antibiotics with gram negative/anaerobic FIRST; Cefepime Aztreonam Levofloxacin Amikacin Metronidazole Administer antibiotics with gram positive coverage SECOND; Vancomycin Administer antibiotics with Fungal coverage THIRD; Fluconazole Caspofungin Rationale: better timing means improved outcomes

Add to Sepsis criteria any one of the following signs that would indicate hypoperfusion and organ dysfunction: Areas of mottled skin Urine output < 0.5 ml/kg for at least 1 hour Lactate > 2mmol/L Abrupt change in Mental Status Abnormal EEG findings Platelets < 100,000 Disseminated intravascular coagulation (DIC) Adult Respiratory Distress Syndrome (ARDS) Cardiac dysfunction

} Systemic mean Blood Pressure < 60 mmhg despite adequate fluid resuscitation (<80 in known hypertensive pt) } Maintaining Systemic mean BP > 60 mmhg requires } Medications Dopamine > 5mcg.kg/min Norepinephrine < 0.25 mcg.kg/min Epinephrine < 0.25 mcg/kg/min

Pressure in the thoracic vena cava Estimates right atrial pressure Estimates right ventricular pressure Estimates right ventricular volume Estimates preload

} Oxygen Saturation of Central Venous hemoglobin } Amount of oxygen left over after the body removes what it needs } Represents the balance between oxygen delivery and consumption

OXYGEN: BALANCE Oxygen balance is necessary to sustain life. SvO2 is the "watchdog" of this balance. When monitored, it serves as an early trouble indicator and can help clinicians adjust therapies. In a healthy individual, normal SvO2 is between 60% and 80% If SvO2 is low (below 60%) then the oxygen supply is insufficient or the oxygen demand has increased. If SvO2 is high (above 80%) then the oxygen demand has declined or the oxygen supply has increased.

} Aggressive fluid resuscitation-5l/6hours } Give in 500 cc bolus and assess for signs of Pulmonary Edema } Intubation and mechanical ventilation } Vasopressors } CVP monitoring } Transfusions for increased tissue perfusion } Inotropic therapies } Sequential serum lactates

} Patient dies as much from the body s response to infection as from the infection itself } Huge epidemiologic burden of sepsis } Recognition is major hurdle } Lactate is a marker for critical illness and can be used as a screening tool

Thank You!