Faheem Guirgis MD, FACEPED and Trauma Symposium – February 16th, 2017Co-Chair Sepsis CommitteeAssistant Professor of Emergency MedicineDivision of ResearchDepartment of Emergency MedicineUF Health Jacksonville

Sepsis: Updates,Pearls and Pitfalls

Disclosures

K23GM115690 – National Institute of General Medical Sciences

Society of Critical Care Medicine Weil Grant for Sepsis

Dean’s Grants from UF

Objectives Briefly discuss updated sepsis definitions Discuss principles of early severe sepsis

management Review pearls and tips for sepsis

management Outline common pitfalls to avoid in sepsis Discuss the implications of recent

literature and potential future changes in sepsis care

A. Under-recognized B. Under-treated C. Misunderstood (pathophysiology) D. All of the above

Sepsis 3?

Confused Scrubs

OLD

NEW

Local Infection

Systemic signs?

Organ Dysfunction (dysregulated response)

Shock

+

SOFA

Start Early, Be Aggressive

1. Figure it out EARLY

Sepsis Screening

2. Fill the Tank = Fluids

IVC US, Dynamic measures, PLR

3. Fight the Bugs

AntibioticsSource Control

4. Fix perfusion MAP Organ fx Lactate Inotropes

The 4 F’s

UF Health Jacksonville Sepsis Committee

Institution-Wide Multidisciplinary Approach

Sepsis Screening/Early recognition protocol (Automated)

Early Management Bundle/Order set Continued Care Bundle Education + Re-education = Culture

of change Chart dives Be Data-driven

FILL THE TANK!

Predicting Fluid Responsiveness Echo/IVC Ultrasound Passive Leg Raise

Pulse Pressure Variation

Stroke Volume Variation

Cardiac UltrasoundQUICK ESTIMATION OF EF – GOOD SQUEEZE OR POOR SQUEEZE

IVC Ultrasound1. Use Cardiac

Probe2. Place probe

in the long axis, SubX, just right of midline

3. Find IVC and measure 3 cm distal to RA (at or distal to HV)

4. Can use M-mode

5. Have patient sniff if spontaneously breathing

IVC Collapse – Spontaneously Breathing IVC < 1 cm = give fluids IVC 1-2 cm w/ 50% collapse w/

inspiration= give fluids IVC > 2 cm or w/o collapse = not

fluid responsive Pulmonary Hypertension/RHF may

confound your IVC US Patients on mechanical ventilation –

look for a 15-18% change in IVC diameter

3 cm

ICU population Vasopressor dependent septic shock All on mechanical ventilation Limited Echo (LE) performed w/in 24

hours of ICU admission

Echo-based Strategy for Shock Resuscitation

1. Systolic function: normal, moderate, or severely impaired

2. Assess for pericardial effusion

3. IVC diameter fluctuation < or > 15%

dIVC=[(dI−dE)/dE]×100

<15% dIVC with normal LV fx = stop fluids

>15% dIVC w/ normal LV fx = 20 to 40 mL/kg fluids

>15% dIVC w/ mod to severe LV dysfx = 10 to 20 mL/kg fluids and dobutamine 5 mcg/kg

<15% dIVC w/ mod to severe LV dysfx = dobutamine and no fluids

Passive leg raise. To perform a passive leg raise, a patient is placed in a semi-recumbent position at 45°. The patient’s legs are then elevated to 45° and the hemodynamic variable of interest evaluated after 30−60 seconds.

So you’ve given fluids…

1. Is fluid resuscitation adequate? - Heart, IVC collapse, PPV, SVV

2. Is MAP adequate? - MAP > 65

3. Is Oxygen Delivery adequate? - Lactate normalization vs Lactate clearance?

Now Go Back and Ask 3 Questions…

What about individual measures of organ function?

FIGHT THE BUGS = ABX + Source Control

2016 AntibioticsEffective Abx within 1st hour for sepsis

and septic shock (2016) Every hour of delay in giving Abx is

associated with a measurable increase in mortality (Kumar et al; Ferrer et al)

Mortality significantly increased in patients who received initial antibiotics after shock recognition (n = 172 [59%]) compared with before shock recognition (OR, 2.4; 1.1-4.5) – Puskarich et al

Consider this:

Gram + > Gram - > polymicrobial as the cause of most septic shock

Bolus drugs before infusion drugs Broad coverage guided by local

prevalence patterns All patients should receive a full

loading dose of antibiotics

Terminology

Empiric Therapy – best guess, no bugs yet

Broad Spectrum Therapy – broad spec abx to cover multiple potential bugs

Combination Therapy – Using more than one drug to cover the same bug (largely unproven)

2016 Antibiotic Recs

Empiric combo therapy for initial management of septic shock

No Empiric combo therapy for regular sepsis or bacteremia

No combo therapy for neutropenic sepsis/bacteremia

If combo therapy is used – de-escalate in the first few days if clinical improvement

Source identification

“Trauma is a compulsive search for injuries” – Billy Mallon

“Sepsis is a compulsive search for a source of infection” – Me Treat the patient like a trauma – fully

expose, etc The less the patient can tell you the

more compulsive the search And…the severity of the source

should be proportional to the severity of illness

2016 Source ControlSource control as soon as

possible (Rec 6-12 hrs from time of diagnosis)

If intravascular device is a possible source, it should be promptly removed after other vascular access established

Consider IR or Surgery

Who cares about cultures? Cultures of blood and other sites

(urine, CSF, wounds, respiratory secretions, etc) before abx if possible

Cultures from vascular access and peripheral blood – 10 cc each

If culture from vascular access is positive earlier than peripheral blood then vascular access = infectious source

DO NOT DELAY ANTIBIOTICS > 45 MIN FOR BLOOD

CULTURES

But…

Fix Perfusion

VASOPRESSORS+

Inotropes

Published in CCM in 2015 Dopamine still a bad choice for SSh Greater hospital mortality –

propensity-matched scoring, n = 38,788; 25% vs 23.7%; OR 1.08; 95% CI, 1.02-1.14)

Most commonly used in the South!

2016 Vasopressors

Norepinephrine 1st agent Vaso or Epi as 2nd agent Epi - especially if inotropy required Vaso – need alpha Phenylephrine if inotropy not needed

Norepi causing arrhythmias CO is high and BP is low Salvage therapy

Dobutamine – first choice inotrope

VANISH trial

Vaso +/- HC vs Norepi +/- HC for vasopressor dependent septic shock

Primary outcome – renal failure free days

No difference Demonstrated that Vaso could be

titrated up to a dose of .06units/min

2016 Lactate

Guide resuscitation to normalize lactate Lactate normalization (< 2) Clearance?

2016 Blood

2016 Steroids

Hydrocortisone 200 mg/day When starting your second pressor

Management Pitfalls

Now what?

Management so far: Fluids Abx Source identified and controlled Pressors Lactate level

Risk of Death?

Prevalence Mortality

Lactate > 4 alone

5.4% 30% butPerhaps 20%

Hypotension alone

49.5% 36.7%

Lactate > 4 + Hypotension

16.6% 46.1%

1316 pts w/ sepsis w/in 4 hrs of ED arrival

111 progressed to shock w/in 48 hrs (8.4%)

Females (OR 1.59), nonpersistent hypotension (OR 6.24), bandemia ≥ 10% (OR 2.6), lactate ≥ 4 (OR 5.3), PMH CAD (OR 2.01)

Beyond Mortality…now what? SEPSIS RECIDIVISM

110 ED patients w/ SS/SSh

28-90 days: 17% rate of sepsis readmission

LONG-TERM MORTALITY Initial mortality 18%

(90 survivors) 3 year mortality 48%

(only 53 survivors)

Chronic Critical Illness Disease of the elderly who survive initial sepsis dc LTAC, functionally dependent, die outside of the hospital months to years later (Sepsis P50 – UF)

Sepsis Recidivism?

Fiscal impact of 30 day sepsis readmissionSepsis CHF Acute MI

Initial Hospitalization (2009-11)

240,198 193,153 105,684

Readmission rate 20.4% 23.6% 17.7%Annual costs (California)

$500 million/yr

$229 million/yr

$142 million/yr

The Future?! Improved sepsis diagnostics (biomarkers)

Dys-HDL? Better understanding of pathophysiology

CCI/PICS/CARS (thanks to UF G’ville – Moore, Moldawer, Leeuwenburgh)

Persistent/long-term organ dysfunction – who/why? Sepsis recidivism – why?

Mitochondrial medicine? RACE Trial - L-carnitine (increases cardiac mechanical

efficiency and facilitates mitochondria) Metabolic cocktails? Hypothermia?! ECMO?

CMS Sepsis Definitions? Old definitions SEVERE SEPSIS: SIRS + sepsis-induced organ

dysfunction: SBP < 90 or MAP < 70 mm Hg Creatinine > 2.0 mg/dl or Urine Output < 0.5 ml/kg/hour

for > 2 hours Bilirubin > 2 mg/dl (34.2 mmol/L) Platelet count < 100,000 Coagulopathy (INR >1.5 or aPTT >60 secs) Lactate > 2 mmol/L

SEPTIC SHOCK: Lactate > 4 mmol/L, OR SBP < 90 or MAP < 70 mm Hg, not responsive to fluids

CMS Management A. measure lactate level B. obtain blood cultures prior to antibiotics C. administer broad spectrum antibiotics D. administer 30 ml/kg crystalloid for hypotension

or lactate = 4 mmol/L E. apply vasopressors (for hypotension that does

not respond to initial fluid resuscitation to maintain a mean arterial pressure = 65)

F. in the event of persistent hypotension after initial fluid administration (MAP < 65 mm Hg) or if initial lactate was = 4 mmol/L, reassess volume status and tissue perfusion and document findings.*

CMS Reassessment 2/4 of the following

Measure CVP Measure ScvO2 Bedside cardiovascular ultrasound Dynamic assessment of fluid responsiveness with

passive leg raise or fluid challenge OR Focused exam† including vital signs,

cardiopulmonary, capillary refill, pulse and skin findings.

Remeasure lactate if initial lactate is elevated

It’s only the beginning!

But sadly, it’s the end of my lecture

Thank you!

a case

2016 SS Guidelines Changes Fluids - 30 ml/kg in the first 3 hours, crystalloid first, then maybe

albumin, use dynamic markers and/or fluid challenges Goal MAP>65 EGDT is no longer recommended Lactate - attempt to normalize lactate Blood Cultures - get them before antibiotics, if obtaining them will

not delay the provision of antibiotics Antibiotics - Within 1 hour of sepsis or septic shock Vasopressors - Norepi is the first choice, add in epi or vaso, Do not

use dopamine Steroids - 200 mg Hydrocortisone for patients who are still

unstable after fluids and vasopressors Blood - In most circumstances, use a trigger of <7.0 g/dL Glucose - goal is < 180 mg/dL Bicarb - Not recommended if pH is >7.15 (which in no way means

it is recommended for pHs less than that)