Approach to Sepsis and Shock K A R E N T R A N P G Y 5 G I M F e - - PowerPoint PPT Presentation

K A R E N T R A N P G Y 5 G I M F e l l o w J U L Y 9 , 2 0 1 5

Approach to Sepsis and Shock

Objectives

 To develop an approach to the evaluation of patient with

fever

 To develop an approach to assess a patient for the presence

• f SIRS, sepsis, severe sepsis, and septic shock

 To learn how to triage and manage patients with sepsis  To learn evidence base management of sepsis  To become familiar with the sepsis protocols

Sepsis in Canada

• 30,000 Canadians are hospitalized for sepsis each year
• 30.5% mortality rate all comers (45.2% with severe

sepsis)

• 9300 sepsis deaths in Canada per year (11% of all

hospital deaths)

• 56% increased death rate if diagnosed after admission

rather than in the ER

• Early recognition and antibiotics increases survival rate

by up to 50%

• Failure to recognize sepsis occurs most commonly in

post-op patients, elderly > 70 years old, or chronically ill/immunocompromised

Canadian Institute for Health Information. 2009

Rationale:

 Sepsis is a serious life threatening medical condition  One of most common admission to hospital/CTU/ICU  Increased awareness, modified triage tools and

targeted management strategies have the potential to improve sepsis outcomes

“… inadequate patient assessment” “However, when detected early and treated aggressively, people can be spared the “ravage of sepsis”

Sepsis Video

 https://vimeo.com/129916157

• Mr. Rivers

 45M presents to ER with 2 day history of fevers  PMHx: Hypertension and Type 2 DM  Medications: Ramipril 10 mg once daily and metformin

500 mg po BID

 NKDA  ROS: Abdominal pain with N/V

What is your approach and differential diagnosis of fever?

Approach to Fever

 M-malignancy (primary, hematologic, metastatic)  A-autoimmune (RA, SLE, vasculitis, CTD)  I-Infection  I-Inflammatory (Pancreatitis, hepatitis, IBD)  D-Drugs (Prescription medications, recreational drugs-

intoxication, withdrawal, NMS, Serotonin syndrome, toxidromes)

 E-Endocrine (Thyroid storm, Pheochromocytoma,

Cushings, Adrenal insufficiency)

 V-Vascular (ACS, PE, HUS/TTP)

What’s your approach to Infections?

Approach to Infectious Causes

 CNS: meningitis, encephalitis, brain abscess  H&N: Sinusitis, Dental abscess  CVS: Bacteremia, Infective endocarditis, myocarditis

Resp: Pneumonia (bacterial, mycobacterium, viral, fungal), Empeyma

 Abdo: Ascending cholangitis, perforation, pancreatitis

complications, abscess, diarrhea (C.diff), peritonitis

 GU: Pyelonephritis, renal abscess, prostatitis, UTI  Gyne: Pelvic abscess  Derm: Cellulitis, Erysipelas, Necrotizing fasciitis  Other: Lines (IHD, portacath for chemo)

How do you recognize sepsis?

Definitions

• Systemic Inflammatory Response System (SIRS)
• Manifested by 2 of the following criteria:
• Temp > 38.30 C or < 360C
• HR > 90 bpm
• RR > 20 or PaCO2 <32
• WBC > 12 or < 4 or > 10% bands
• Infection: Pathological process caused by invasion of

normal sterile fluid/body cavity by pathogenic or potentially pathogenic microorganisms

Dellinger RP et al. Intensive Care Med. 2013l 39(2):165-228.

Definitions

• Sepsis = SIRS + suspected/potential source of infection
• Severe Sepsis = Sepsis + end organ dysfunction or

hypoperfusion

• Septic Shock = Sepsis + hypotension (SBP < 90, MAP

< 70 or SBP decrease > 40 from baseline) not resolved with fluids

Dellinger RP et al. Intensive Care Med. 2013l 39(2):165-228

Dellinger RP et al. Intensive Care Med. 2013l 39(2):165-228

!

inflammation ischemia trauma SIRS infection

→

Sepsis

→

severe sepsis

→

septic shock

!

clinical insult 2 of the following:

! temp >38.3° or <36° ! WBC >12000,<4000,>10% IB ! HR > 90 bpm ! RR>20 or PaCO2 <32 mmHg

sepsis with BP <90mmHg or <70mmHg MAP despite adequate fluid resuscitation SIRS w/ organ hypoperfusion or

• rgan dysfunction

MODS

!

! urine output <0.5ml/kg/h ! lactate >4mmol/L ! Cr>177mmol/L ! Plt<100000mL ! bili>34mmol/L ! INR>1.5 ! ALI PaO2/FiO2<250 ! ALI PaO2/FiO2<200 w/ p

Dellinger RP et al. Intensive Care Med. 2013l 39(2):165-228

Organ Dysfunction

 CNS  Metabolic encephalopathy  CVS  Shock, demand ischemia  Resp  Acute lung injury, ARDS  GI  Gastroparesis, ileus  Liver  Cholestasis  Kidney  Acute tubular necrosis  Heme  Coagulopathy (DIC)  Endo  Adrenal insufficiency

Approach to Shock

 Definition: Acute circulatory failure resulting in

hypoperfusion and end organ injury

 Does not necessarily imply hypotension  Patients can have “normal BP” and have relative

hypotension if BP is normally high

Types of Shock

 Etiologies

 Cardiogenic = pump failure  Distributive = peripheral vascular resistance failure  Hypovolemic = lack of fluid/blood

BP = CO x SVR

HR x Stroke Volume

Preload Afterload Contractility

BP = CO x SVR

HR x Stroke Volume

Distributive Shock Cardiogenic/Obstr uctive Shock

Preload Afterload

Hypovolemic Shock

Contractility

Approach to Shock

 S-septic  H-hypovolemic

 20 GI loss, hemorrhage, burns, third spacing, pancreatitis

 O-obstructive

 PE, RV infarct, tamponade

 C-cardiogenic

 ACS, heart failure

 C-catch all

 Anaphylaxis, neurogenic shock

Hemodynamic Profiles of Various Forms of Shock

Type of Shock RA PCWP CO SVR Sepsis Variable Variable   Hypovolemic     Obstructive  N or    Tamponade     Cardiogenic N or    

Sepsis Management

1.

Recognize

• clinical experience
• screening tools

2.

Triage

• Order appropriate investigations, esp: lactate and cultures
• IV fluids and IV antibiotics
• Consult appropriate health care providers (ICU)

3.

Respond

• early goal directed therapy

“The speed and appropriateness of therapy administered in the initial hours after severe sepsis develops will have a large influence on outcome”

Sepsis Management

 ABC  MOVII

 Monitored setting, Oxygen, Vital signs, IV access, Investigations

 IV fluids with crystalloid  Broad spectrum IV antibiotics  Oxygen supplementation  Early Goal Directed Therapy

Sepsis Management

 Early Goal Directed Therapy

 CVP 8-12 mm Hg  MAP > 65 mm Hg  ScVO2 > 70%  Urine output ≥ 0.5cc/kg/hr  Target lactate as marker of hypoperfusion

 Source Control – early OR for debridement, ERCP in

cholangitis, chest tube for empeyma, etc.

 Ask for help

 Senior residents, staff physician, CA  Consult ICU early if not responding to medical therapy

What investigations would you want to order?

Investigations

 CBCD  Peripheral blood smear  Lytes, BUN, Cr  Lactate  INR, PTT  Liver enzymes  Troponin  BCx x 2  U/A, Urine C&S  CXR PA/lateral  ECG  Consider:  Sputum C&S  CT head +/- LP  CT Abdo  Abdo U/S (if elevated LFT

and Bili)

 Influenza NP Swab

Rivers et al. NEJM. 2001. 345(19):1368-1377.

Rivers Trial

 263 patients presenting to urban ER with sepsis or septic

shock prior to admission to ICU

 Randomized to EGDT vs. standard care  Primary endpoint: in hospital mortality  EGDT decreased mortality among patients with severe

sepsis or septic shock (30.5% vs. 46.5%)

Rivers et al. NEJM. 2001. 345(19):1368-1377.

Rivers et al. NEJM. 2001. 345(19):1368-1377.

NNT of 6 to prevent one hospital death

Criticisms

 Single center study, ED staff not blinded to treatment  Difficult to determine which intervention was the most

successful

 ScvO2 and CVP monitoring is controversial  RBC transfusion is controversial as other studies TRICC

and TRISS have shown increased mortality with liberal blood transfusions

 Control group had an above average mortality

Rivers et al. NEJM. 2001. 345(19):1368-1377.

So what do we do?

Approach to Sepsis Management

 1. Target CVP 8-12 with IV crystalloid for hypotension or

lactate >4 mmol/L

 Clinical volume assessment with JVP, urine output, U/S

 2. Target MAP > 65 mm Hg

 If MAP < 65, consult ICU for IV vasopressors (norepinephrine)

 3. Target ScvO2 > 70% or lactate clearance

 If ScvO2 < 70% and Hct > 30%, start IV inotropes (dobutamine)  If ScvO2 < 70% and Hct < 30% or Hg <70, transfuse 1 U PRBC

Volume Resuscitation

 Crystalloid preferred for hypotension or elevated lactate

 Use NS or Ringers Lactate for bolus  If patient acidotic or severe sepsis consider Plasmalyte

 Aim for 30 cc/kg  No survival benefit with colloid (hydroxyethyl starches)  Reassess the patient to see if intervention is improving

hemodynamics, volume status, urine output and lactate clearance

Vasopressors

 Aim for MAP >65 mm Hg  Need central line/arterial line  Consult ICU early  Preferred agent is norepinephrine (same as levophed)

 Mostly α-adrengeric effect with vasoconstriction

 Could consider low dose vasopressin (0.03 U/min) to be

added to levophed

De Becker et al. NEJM. 2010. 362(9): 779-89.

SOAP Trial

 No difference in all-cause

mortality between the two groups

 Significantly, more

arrhythmias in dopamine group (24.1% vs. 12.4%; NNH 9)

 Bottom Line:

Norepinephrine is first line vasopressor for shock

De Becker et al. NEJM. 2010. 362(9): 779-89.

Common pimping trial in SPH ICU!

Russell et al. NEJM. 2008. 358(9); 877-887.

VASST Trial

 Vasopressin (ADH) elevate BP through smooth muscle V1

receptor mediated vasoconstriction

 779 patients with septic shock were randomized to low-dose

norepinephrine vs. low dose vasopressin

 No difference in all cause mortality at 28 days  Subgroup analysis suggested survival benefit for vasopressin in

less severe sepsis

 Bottom Line: Not recommend as first line vasopressor, but can

be added as salvage therapy to achieve MAP goal

Russell et al. NEJM. 2008. 358(9); 877-887.

Oxygen Delivery (DO2)

 Mixed venous oxygen or ScvO2 is used to assess balance of

tissue oxygen delivery and consumption

 If venous is low, it suggests poor oxygen delivery to tissues  When DO2 drops below critical value, shift to anaerobic

metabolism  lactate production

 DO2= CO x O2 carry capacity  DO2= CO x (Hgb x 1.34 x SaO2 + 0.0031PaO2)

 CO= HR x SV

Oxygen Delivery

 Improve oxygen delivery by:

 Supplemental oxygen +/- mechanical ventilation  Increase cardiac output with inotropes  Preferred agent dobutamine (20 mcg/kg/min) to achieve ScvO2 >

70%

 Mediated by β-adrenergic system to increase inotropy and

chronotropy

 Can get vasodilator response and drop BP  Blood transfusion to improve oxygen carrying capacity

(controversial in real life)

 Consider 1 U PRBC if Hg < 70

Lactate Clearance

 Lactate clearance = (lactate initial – lactate delayed)/lactate

initial x 100%

 Patients with severe sepsis or septic shock with lactate >

4mmol/L randomized to lactate clearance of at least 10%

• vs. ScvO2 monitoring

 Patients had EGDT as per Rivers  No significant difference in in-hospital mortality between

the two groups

Jones et al. JAMA 2010; 303:739-746.

Lactate Clearance

 Patients admitted to ICU with lactate > 3 mEq/L  Randomized to treatment guided by lactate clearance

(decrease lactate by 20%/2h during first initial 8 h ICU stay) or control

 Patients in the lactate group had significantly reduced

hospital mortality (33.9% vs. 43.5%)

 Lactate monitoring has clinical benefit

Jansen et al. Am J Respir Crit Care Med 2010, 182(6): 752-761.

Lactate Clearance

 Bottom Line: Lactate clearance (>20%/2h) is as effective

as ScvO2 to guide resuscitation

 Check lactate frequently as a tool to reassess hypoperfusion  Surviving Sepsis Guidelines: Target resuscitation with

normalizing lactate levels

Jones et al. JAMA 2010; 303:739-746.

Other Important Things to Do

Diagnosis

 Cultures as clinically appropriate before antimicrobial

therapy if no significant delay (>45 min)

 Need 2 sets blood cultures (both aerobic and anaerobic)  One set should be peripheral  Obtain from vascular access device if present  Culture from other sites as indicated:  Sputum Cx, LP, UCx, NP swabs for viral URTI

 Perform imaging studies promptly to confirm potential

source

 CXR, AXR, Abdo U/S, CT Abdo, Echo

Anti-microbial Therapy

 Administration of effective IV Abx within 1 hour of

recognition of sepsis

 8% increase in mortality for every hour of delayed Abx  Initial empiric Abx should be broad  Likely organisms: Gram positive, gram negative, including

MRSA, highly resistant GNB +/- anaerobes

 Important to review patient microbiology to see which

• rganisms they have been exposed to and assess resistance

patterns

 Abx should be reassessed daily for potential de-escalation

Kumar et al. Crit Care Med 2006; 34: 1589-96

Empiric Antibiotic Choices

 CAP

 3rd generation cephalosporin + macrolide

 Ex: Ceftriaxone + azithromycin (doxycycline)

 Fluroquinolone (Ex: Moxifloxacin)

 Febrile neutropenia

 Piptazo or Carbepenem (meropenem, imipenem)

 Urosepsis

 3rd generation cephalosporin (ceftriaxone) or fluroquinolone (cipro)  If history of Enterococcus, consider Piptazo/carbepenem

 Intraabdo (Gram –ve, anaerobes)

 Cipro/ceftriaxone + Flagyl, Piptazo or Carbepenem

Empiric Antibiotic Choices

 Skin and soft tissue

 IV Ancef or Vanco (if history of MRSA)  IV Clindamycin if concerned about necrotizing fascitis

 Meningitis

 IV Ceftriaxone 2 g IV q12H + IV Vancomycin  If elderly, very young, or immunocompromised add: ampicillin

 Pseudomonas

 Piptazo, Carbepenem, Cipro or Aminoglycoside

 MRSA

 Vancomycin or Linezolid

 Source unknown and clinically unwell

 Piptazo/Carbepenem + Vancomycin

Source Control

 Need to determine anatomic source of infection  Source control should be achieved within 12 hours  Percutaneous preferred over surgical drainage  Potential sites of infection

 Pleural space  empeyema  Joint space  septic joint  Intraabdomen  abscess  Biliary system  cholangitis  Endovascular  endocarditis

New Evidence

Angus et al. NEJM. 2014. 370(10): 1683-1693.

ProCESS

 Multicenter trial randomized 1,341 patients with septic

shock

 Inclusion criteria: SIRS + refractory hypotension or lactate

> 4 mmol/L

 Randomized to either protocol based EGDT vs. protocol

based standard therapy vs. usual care

 Primary outcome was rate of in hospital death at 60 days

Angus et al. NEJM. 2014. 370(10): 1683-1693.

Angus et al. NEJM. 2014. 370(10): 1683-1693.

Angus et al. NEJM. 2014. 370(10): 1683-1693.

ProCESS Results

 No mortality differences between the 3 arms EGDT vs.

standard protocol vs. usual care (21% vs. 18.2% vs. 18.9%)

 More fluids was administered in the standard protocol arm

compared with EGDT and usual care in the first 6 hours (3.2L vs. 2.8 L vs. 2.3 L)

 EGDT arm administered more vasopressors, inotropes and

blood transfusions compared to other arm

Angus et al. NEJM. 2014. 370(10): 1683-1693.

ProCESS

 Among patients with early septic shock, there was no difference

in all cause in hospital mortality at 60 days with management driven by EGDT, a novel protocol based therapy or usual care

 Universal invasive monitoring may not be needed  Early recognition is key to improving outcomes in sepsis  Protocol based approach is heavily influenced by Rivers trial  Similar results were confirmed in other large multicenter studies

(ARISE, ProMISe)

Angus et al. NEJM. 2014. 370(10): 1683-1693.

Steroids

 Annane Trial (2002) showed survival benefit associated with

hydrocortisone and fludrocortisone in patients with relative adrenal insufficiency

 CORTICUS Trial (2008) randomized 499 patients with septic

shock to receive hydrocortisone or placebo

 No survival benefit with hydrocortisone, but had a more rapid

reverse of shock and superinfection

 Bottom Line: Do not use steroids if adequate fluid

resuscitation and vasopressors can restore hemodynamics

 If unable to do so, hydrocortisone 50-100 mg IV q6-8h

Sprung et al. NEJM. 2008. 358(2): 111-124 Annane et al. JAMA. 2002. 288(7):862-871.

Activated Protein C

 No longer FDA approved  No improvement in mortality  No longer recommended by Surviving Sepsis Guidelines

Back to Our Case

• Mr. Rivers

 O/E: 380C, HR 110 reg, BP 85/40, RR20, 94% RA  Gen: Diaphoretic, unwell  H&N: No LN  Chest: Clear  CVS: Normal HS, no EHS/murmurs, JVP flat  Abdo: Tender RUQ, no rebound tenderness  Ext: No active joints, no rash

• Mr. Rivers

 His BP improves to 120/70, HR 100  Labs:  WBC 15, PMN 12, Hg 110, Plts 110  Lytes normal, Cr 120 (baseline 50)  Lactate 4.1, Troponin 0.15  AST 300, ALT 250, Total bili 60  U/A –ve  CXR normal  ECG: Sinus tachycardia, no dynamic ST changes  BCx Pending

• Mr. Rivers

 RN calls you for low urine output:

• Mr. Rivers

 RN calls you for low urine output:  BP 70/40, HR 130, T38, RR 26, SpO2 90% on 3L  Repeat labs: WBC 18, lactate 5, Cr 170

• Mr. Rivers

 RN calls you for low urine output:  BP 70/40, HR 130, T38, RR 26, SpO2 90% on 3L  Repeat labs: WBC 18, lactate 5, Cr 170  What do you want to do now?  Who do you want to call for help?  What else would you add to your management?

• Mr. Rivers

 ICU is consulted, and he is brought to the ICU for

mechanical ventilation and vasopressors

• Mr. Rivers

 ICU is consulted, and he is brought to the ICU for

mechanical ventilation and vasopressors

 Can you outline how you would manage him in the ICU?  What else would you want to consider for definitive

management?

• Mr. Rivers

 CT Abdo shows dilated CBD, no other source of

intraabdominal abscess

• Mr. Rivers

 CT Abdo shows dilated CBD, no other source of

intraabdominal abscess

 GI consult regarding source control with ERCP and

successful removes a gallstone

• Mr. Rivers

 CT Abdo shows dilated CBD, no other source of

intraabdominal abscess

 GI consult regarding source control with ERCP and

successful removes a gallstone

 Blood cultures: E. Coli sensitive to Cipro and cephalosporin

• Mr. Rivers

 CT Abdo shows dilated CBD, no other source of

intraabdominal abscess

 GI consult regarding source control with ERCP and

successful removes a gallstone

 Blood cultures: E. Coli sensitive to Cipro and cephalosporin  He clinical improves with early recognition of sepsis, IV

fluids, IV antibiotics, source control and early goal directed therapy.

Sepsis Timeline

 1. Assess patient for ABC, stability, MOVII

 2. Order up front investigations

 CBCD, lytes, BUN, Cr, lactate, LFT, INR/PTT, BCx, U/A, UCx,

CXR, Troponin, ECG

 3. Start IVF (1L NS/Plasmalyte/Ringers Lactate bolus)  4. Order broad spectrum antibiotics  5. Hx and PE to determine etiology of sepsis  6. Review labs to assess severity/organ dysfunction  7. Reassess patient q1h ABC, VS, volume status, u/o  8. If lactate elevated, check q2-4h  9. Consult ICU if worsening respiratory status, hemodynamics,

lactate despite fluids for vasopressors +/- intubation

 10. Source control

Take Home Points

 Early recognition and treatment of sepsis is key  Early fluid resuscitation, IV antibiotics and source control

is important

 Constant reassessment is necessary with vital signs, urine

• utput and lactate clearance

 Always ask for help from senior residents, attending staff,

ICU, subspecialist (ID, GI, Resp), and surgery

References

 Canadian Institute for Health Information. 2009  Dellinger RP et al. Surviving Sepsis Guidelines. Intensive Care

• Med. 2013l 39(2):165-228.

 Rivers et al. NEJM. 2001. 345(19):1368-1377.  Jones et al. JAMA 2010; 303:739-746.  Jansen et al. Am J Respir Crit Care Med 2010, 182(6): 752-761.  De Becker et al. NEJM. 2010. 362(9): 779-89.  Russell et al. NEJM. 2008. 358(9); 877-887.  Kumar et al. Crit Care Med 2006; 34: 1589-96.  Angus et al. NEJM. 2014. 370(10): 1683-1693.  Annane et al. JAMA. 2002. 288(7):862-871.  Sprung et al. NEJM. 2008. 358(2): 111-124.

Questions?