SepsisAlan Batt,

Clinical Educator, CCP

Sepsis…so what?

• 8,000,000 people per year worldwide die from sepsis• Someone dies from sepsis every 2 minutes• The overall mortality rate for patients severe sepsis

is 35% - approximately 5 times higher than for STEMI and stroke• We could save 10-15% with early recognition &

treatment

Sepsis…so what?

Sepsis…so what?

• For every hour that appropriate antibiotic administration is delayed, there is an 8% increase in mortality• Around 40-50% of patients diagnosed with sepsis in

the ED are admitted via ambulance

What is Sepsis?

• It is a profound systemic inflammatory response to an infection.• An infection triggers the inflammatory response to

the presence of microorganisms in normally sterile host tissue

SIRS

• Systemic Inflammatory Response Syndrome is a systemic inflammatory response resulting from activation of the immune system in response to any physiologic insult (regardless of the cause). • Two or more of the following must be present:• Temp >38 or <36 degrees Celsius • Heart rate >90• Resp rate>20 or PaCO2 <32mmhg• WBC >12,000 or <4,000 or >10% immature

forms

Defining Sepsis

• Sepsis is SIRS plus a confirmed or suspected infection (bacterial, viral, fungal or parasitic). • It can be a complication following burns,

trauma, surgery, or illness. • Widespread inflammation, coagulation and

suppression of fibrinolysis occurs.

Defining SepsisIs the patient history suggestive of new infection?• Pneumonia• UTI• Acute abdomen infection• Meningitis• Skin/soft tissue infection• Bone joint infection• Wound infection• Catheter related Blood stream infection• Endocarditis• Implantable device infection

Adapted from Bone, R. C., Sibbald, W. J., & Sprung, C. L. (1992). The ACCP-SCCM consensus conference on sepsis and organ failure. Chest, 101(6), 1481–3.

Severe Sepsis

• Severe sepsis is sepsis associated with the dysfunction of one or more organs. • Hypotension and hypoperfusion with lactic acidosis

occurs. • Low blood pressure, high lactate levels and signs of

organ dysfunction are seen.• The patient may also exhibit chills, tachypnea,

tachycardia, poor capillary refill and petechiae

Transitioning to Severe Sepsis• The Signs of Severe Sepsis• Arterial hypoxemia (PaO2/FIO2 <300)• Spo2 <90% on Room air or supplemental O2• Acute oliguria (UO<.5ml/kg/hr)• Acutely altered mental status• Creatinine >2.0• Bilirubin >2.0• Thrombocytopenia plt <100,000• Lactate > 4 mmol/L• SBP <90 MAP<65 * *These are the classic

indicators to trigger EGDT• Coagulopathy INR>1.5 PTT>60

Septic Shock

• Is acute circulatory failure unexplained by other causes• Patient has persistent arterial hypotension SBP<90

[MAP <60] despite adequate volume resuscitation• Patients don’t always look “sick” until this point

SIRS…a progression

Infection → sepsis → severe sepsis → septic shock → MODS → death

• Mortality is 50-60% in septic shock• Early intervention is key• We need to identify patients quickly and initiate treatment

Bundles • Bundles are a group of interventions based on scientific

evidence

Understanding Sepsis

• Gram neg organisms cause most of adult cases• E. Coli, Klebsiella, Enterobacter and Psuedomonias

• Gram positive organisms such as staphylococcus, streptococcus, pneumococcus and enterococcus cause others (these are associated with invasive devices)• Viruses, Protozoa, parasites, fungi (Candida) and anaerobic

organisms like Clostridium can also cause sepsis• Most common sites of origin are• Skin and wounds, GI, Respiratory, Urinary tract

Understanding Sepsis

• Regardless of what caused it, the inflammatory response is the same and is designed to help the body fight infection and repair itself.• SIRS is local inflammatory response that gets out of control.• An avalanche of chemical mediators is set off that leads to

tissue/organ damage• Endotoxins from bacteria signal release of cytokines and

other mediators that circulate throughout the body and cause a number of responses:

Understanding Sepsis

• Systemic vasodilation which causes hypotension and decreased afterload (SVR)• Increased capillary permeability which causes edema and

decreased preload (CVP)• Platelet aggregation, fibrin deposits and activation of

clotting cascade cause microcirulatory coagulation & further tissue hypoxia and other chemicals prevent the breakdown of these clots

Understanding Sepsis

• Multiple organ dysfunction results due to hypoperfusion caused by the hypotension, hypovolemia and thrombus formation.• Hypermetabolic state where the body breaks down fat and

muscle for energy• As tissue damage progresses, more organs begin to fail

ultimately leading to death• Early intervention is the key

Treating Sepsis

• Goal is to identify patients with Severe Sepsis And Septic Shock early

& • Initiate treatment using the Early Goal-Directed

Therapy Protocols and following the Surviving Sepsis Guidelines

Who is at risk?

• Very young and very old• Those who have a compromised immune system e.g.. Patients

on steroids, chemo, pneumonia• Have wounds or injuries (burns/ trauma)• Have alcohol or drug addiction• Any one with intravenous catheters, wound drainage, urinary

catheters etc.• Those with malnutrition (TPN)• Pts with no spleen • Recent surgery• Diabetics

Identifying Risk for Sepsis

• Patients who are admitted to the hospital with serious diseases are at the highest risk of developing sepsis because of: • Their underlying disease • Their previous use of antibiotics • The presence of drug-resistant bacteria in the hospital • The fact that they often require invasive tubes or lines.

Especially if intubated/mechanically ventilated >48hours

Identifying Sepsis

What do these patients look like?• Fatigued, anorexic• Fever (or hypothermic)• Edema• Tachycardic• Tachypnoea and or dyspnoea• Altered mental status (especially >65)• Hypotensive• Skin may be flushed, warm and dry or cool and mottled

Identifying Sepsis

• Look for:• Low SpO2, abnormal blood gases• CO2 may decrease as an early attempt to

compensate for lactic acidosis• Low urine output, creatinine >2• Abnormal WBC (high or low)• Hyperglycemia (serum glucose elevates as part of the

stress response)• Abnormal coagulation studies• High bilirubin• Key signs are SBP <90 or lactate >4• Cultures can help identify infection and source

Case 1

• 78 year old male presents awake, confused, and in moderate distress• Emesis in basin at

bedside• When asked, patient

states “I’m weak, and don’t feel well”• Skin is pale, dry

Case 1

• General Impression: Patient responds to your questions. GCS = E-4, V-4, M-6• Airway: Patent, no stridor• Breathing: tachypneic, tidal

volume slightly shallow• Circulation: tachycardic

and weak radial pulse, capillary refill 4 seconds• Skin dry, pale, warm

Case 1

• S: Son states that patient is “slightly more confused” than normal over the past 24 hours. Patient states he “feels sick and weak”, has abdominal pain, and is vomiting.

• A: Aspirin• M: Insulin• P: Dementia, IDDM• L: light breakfast 2 hrs ago• E: Progressively worse nausea

and vomiting over past day.

• Vital signs: HR = 88, RR = 26 normal TV, BP = 96/52, SpO2 = 98% room air up to 100% with cannula

• Lung sounds: slight expiratory wheezing and crackles in middle right lobe

• Skin dry and warm to touch• Mucus membranes dry, skin

turgor poor• Oral temperature = 100.3°F• Good tidal volume

Case 1

Case 1

Case 1

• Differential diagnoses?

• Treatment plan?

• Treatment priorities?

Resuscitation Bundle:Tasks in the First 3 - 6 Hours1. Measure serum lactate

2. Obtain Blood cultures prior to antibiotic administration

3. Administer broad spectrum antibiotic within 3 hrs if in ED (1 hr if inpatient)

4. In event of hypotension and/or lactate >4a. Deliver initial fluid bolus of 20cc/kg crystalloid or

equivalentb. Vasopressors for hypotension not responsive to initial

fluid to maintain MAP > 65

5. For persistent hypotension despite fluid resuscitation (septic shock) and/or lactate >4mmol/L

a. Achieve CVP >8b. Achieve ScvO2 > 70% or SvO2 > 65%

NNT

• PCI in STEMI = 45-90• TXA in trauma = 67• Aspirin in AMI = 42• CPAP for pulmonary oedema = 13• Sepsis Six = 4.6!• Defibrillation in cardiac arrest = 2.5

Management BundleFirst 24 hoursConsider low dose steroids for septic shock according to a

standard policy• Or document why it is not appropriate

Consider human activated protein C (XIGRIS) according to a standard policy• Or document why it is not appropriate

Maintain glucose control >120 but <180Maintain median inspiratory plateau pressures <30 for

mechanically ventilated patients

Treating Sepsis

• Rapid placement of a central venous line is priority• IJ or SC• To measure CVP and ScVO2

• Fluid challenges are given to • CVP 8-12 (15-18 if mech vent)• SBP >90 or MAP >65• UO > 0.5ml/kg/hr• Levophed is started if hypotension is unresponsive to fluid

• For ScVo2 <70• If Hgb <7 consider transfusing blood to goal of Hgb 7-9g/dl• Dobutamine is started if ScVo2 still <70

• O2 therapy or intubation/ventilation if needed

Treating Sepsis

• Transfer to ICU ASAP• Central line is priority if not already in• Arterial line may be needed to monitor blood

pressure• Continue sepsis protocols

• Fluid for CVP <8 MAP <65• Vasopressor if not fluid responsive• Inotrope and transfusion for ScVO2 <70 and Hg <7

• Monitor CVP, ScVO2, lactate every 30 min• Until goals met

Treating Sepsis

• Continuing Treatment• Airway Ventilator management• HOB is at 30 degrees & mouth care to prevent VAP• DVT prophylaxis• Plateau pressures < 30• Weaning assessed daily

• Consideration of hydrocortisone 50mg IV Q 6 hrs for 7 days • Strict glucose control >120 to <180 with protocol or

sliding scale (median glucose of 140)• Consider Xigris (Activated protein C)

Treating Sepsis

• Other Considerations• Nutrition is important due to the hyper-metabolic state• Skin care and assessment to prevent breakdown• Sedation, analgesia, paralytics, must be used cautiously

to optimize ventilation yet prevent prolonged intubation• RAAS / Pain scales are used to measure patients

progress• Strict I/O Use foley catheters only if truly necessary

Case 2

• 44 y/o female• Lying in bed• Opens eyes when you

say “hello”• Seems confused• Skin pale, slightly moist

Case 2

• Conscious, alert to verbal stimuli, confused to person, place, time• Airway: open• Breathing: normal rate

and tidal volume• Circulation: weak,

tachycardic radial pulse, cap refill 4 seconds• Skin warm, slightly moist

Case 2

• S: Patient complains of weakness. Husband reports a 3 day historyof worsening AMS, patient normally conscious, alert, and oriented.

• A: NKDA• M: Glyburide, propranolol,

nifedipine• P: AMI 3 years prior, HTN, Type

II DM, recent UTI• L: Breakfast this morning• E: No known events that

precipitated AMS

• Vital signs: HR = 92, BP = 88/42, RR = 20 and regular tidal volume, SpO2 = 96% RA up to 100% with oxygen 4 lpm via cannula

• Mucus membranes dry, poor skin turgor

• Skin warm to touch, slightly moist

• Temperature = 98.8°F via oral thermometer

Case 2

Case 2

Case 2

• Differential diagnoses?

• Treatment plan?

• Treatment priorities?

Highlights from the Guidelines• Supplemental oxygen• Sepsis causes an imbalance between tissue oxygen

supply and demand. Adequate tissue oxygenation is essential to the treatment of a patient with sepsis. • Continuous pulse oximetry is performed. Supplemental

oxygen is utilized to maintain the oxygen saturation ≥ 94%.

Antibiotic Therapy

• Intravenous antibiotic therapy should be started within the first hour of recognition of severe sepsis, after appropriate cultures have been obtained. • Broad-spectrum agents are ordered initially. • This treatment should be reevaluated after culture results

are available.

Fluid Therapy

• Two large bore peripheral catheters should be inserted initially and a central venous catheter should be placed ASAP. • Fluid resuscitation (the number one priority) is

accomplished with either crystalloids or colloids. Neither has been proven to be better than the other. • The target is to maintain a CVP between 8-12 mmHg, with a

higher CVP recommended for a mechanically ventilated patient. (due to positive pressure ventilation) • RASP trial ongoing comparing Ringers v Albumin

Vasopressor Therapy

• Once fluid resuscitation has been accomplished, if adequate blood pressure and organ perfusion has not been restored, vasopressor therapy should be started. • Norepinephrine is the initial vasopressor of choice.• Phenylephrine may be considered.• An arterial catheter should be placed as soon as possible for

monitoring of arterial pressures and blood gases. • Vasopressin may be added in patients with refractory shock

despite adequate fluid resuscitation and high dose vasopressor agents.

Inotropic Therapy

• In patients with low cardiac output despite adequate fluid resuscitation, dobutamine may be used to increase cardiac output. • If the blood pressure is low, it is used in combination

with a vasopressor. • ScVO2 of >70% is the goal.

• Blood transfusion should be considered if Hgb is less than 7 to optimize the oxygen carrying capacity of the blood.

Steroids

• IV corticosteroids (hydrocortisone 200-300 mg/day for 7 days in 3 or 4 divided doses or by continuous infusion) are recommended in patients in septic shock who, despite adequate fluid replacement, require vasopressor therapy to maintain an adequate blood pressure. • Corticosteroids must be started when the patients BP is

refractory to vasopressor therapy.• Once vasopressor therapy is no longer required, steroid

therapy can be weaned.

Blood Product Administration• The recommendation is to transfuse packed red blood cells

when the hemoglobin decreases to < 7 g/dl. • This optimizes the oxygen carrying capacity of the

patients blood. • Platelets may be needed for those patients with a platelet

count <50,000 mm3.

Glucose Control

• Hyperglycemia and insulin resistance occur in severe sepsis. • Tight glucose control with insulin is used to maintain blood

glucose 6.5-10 mmol/L [120-180 mg/dl]• Hypoglycemia has shown to cause higher mortality in critical

patients.• Insulin protocols should be followed.

Mechanically Ventilated Patients• Maintain Inspiratory Plateau Pressure < 30 cm H2O)• Patients with sepsis are at increased risk for developing

acute respiratory failure. Most patients with severe sepsis and septic shock will require mechanical ventilation. • Nearly 50% of patients with severe sepsis will develop acute

lung injury (ALI (acute respiratory distress syndrome). • High tidal volumes along with high plateau pressures should

be avoided. • The goal is to maintain a tidal volume of 6mL/kg lean

body weight in addition to end-inspiratory plateau pressure < 30 cm H2O.

Bottom line?

• Everyone with suspected sepsis needs to get to hospital…quickly!• Everyone should get high flow oxygen – regardless

of SpO2 reading!• Everyone should get fluids if they’re in shock• Pre-alert the ED and mention the word “sepsis”• Sepsis kills – let’s stop it – the simple stuff saves

lives

More information

• http://www.survivingsepsis.org• http://www.uksepsis.org/ • http://sepsistrust.org/• http://www.cdc.gov/sepsis/