Mangement of sepsis and septic shock

Management of a child with sever

Sepsis and Septic Shock

Prof. Hamida Esahli

Head of PICU Elkhadra Hospital

Date: 12/09/2013

Event : World Sepsis Day in Libya

Title: This is the footer

Date: 13th September 2013

Slide no: 2

OBJECTIVE;

Identifying sepsis

•What do we look for in sepsis?

•Which patients get sepsis?

•What is sever sepsis?

•What is Septic Shock?

•What is Sepsis six?



Slide no: 3

SEPSIS• Sepsis is one of the oldest and most elusive syndromes in

medicine.

• 1.Hippocrates claimed that sepsis (σ ´ηψις) was the

process by which flesh rots, swamps generate foul airs, and

wounds fester. Galen later considered sepsis a laudable

event, necessary for wound healing.

• 2 With the confirmation of germ theory by Semmelweis,

Pasteur, and others, sepsis was recast as a systemic

infection, often described as“bloodpoisoning,”and assumed

t be the result of the host's invasion by pathogenic

organisms that then spread in the bloodstream



Slide no: 4

Who are risk groups?

Old

Young

Ill

Infections

Malignancy

How many of your patients are included?

Compromised organs

Immunocompromised

Post chemotherapy

Malnutrition

Invasive lines



Slide no: 5

The Pathogenesis of Sepsis

Response to Stimulus

•Inflammation

•Immunosuppression

•Coagulopathy

•Mitochondrial dysfunction

Infectious Agents

•Endotoxin/LPS

•Lipopeptides

•Lipoteichoic acid

•DNA

•Flagellin

Susceptible Host

•Co-morbidities

•Age

•Genetic polymorphisms

SEP

SIS



Slide no: 6

Infectious or no ninfecectiousinsult

Systemic inflammatory response(SIRS)

Miocrovascular:Endothelial function

Micro emboliGut mucosa ischemia

Hemodynamic: vasodilatation Myocardial

depression Redistribution/Shunting

O2 hypoxiaOrgans

CellMitochondria

Cellular damage/apoptosis

MODSCNS –CVS-Renal-Hepatic-pulmonary-Hematology

Basic Pathophsiology



Slide no: 7

Definitions

Infection Inflammatory response to

microorganisms, or

Invasion of normally sterile

tissues

Systemic Inflammatory

Response Syndrome (SIRS) Systemic response to a

variety of processes

Sepsis Infection plus

2 SIRS criteria

Severe Sepsis Sepsis

Organ dysfunction

Septic shock Sepsis

Hypotension despite fluid

resuscitation

Bone RC et al. Chest. 1992;101:1644-55.



Slide no: 8

Step 1: Is SIRS present?

A systemic response to a nonspecific insult

Infection, trauma, surgery, massive transfusion, etc

Defined as 2 of the following:

• Temperature > 38.3 or < 36 0C

• Heart rate in infant<90>160pmb

• in child<70>150bpm

• Respiratory rate >2SD above age

• AVPU V, P or U

• White cells < 4 or > 12

• If not diabetic, blood sugar >140mg/dl/l



Slide no: 9

Step 1: Is SIRS present?

Why do we see SIRS??

Temperature: ‘Pyrogens’ raise body temperature. Later, temperature drops

as we lose excess heat

HR: To stop B.P falling, heart rate rises

RR: The body needs more oxygen in sepsis, and tissues produce

more acid. RR increases to help with both.

AVPU: As B.P and cardiac output fall later in sepsis, blood flow

to the brain reduces

White cells: Rise to combat infection. As they are used up, if bone

marrow is exhausted WCC falls

Blood sugar: Rises as part of our ‘stress response’



Slide no: 10

Bacteria

Virus

Fungi

Parasite

Infection SIRS

Sepsis

Pancreatitis

Trauma

Infection

Other

Severe

Sepsis



Slide no: 11

SIRS = Systemic Inflammatory Response Syndrome

SepsisSIRSInfection/Trauma

Severe Sepsis

, et al. Chest 1992;101:1644, Opal SM, et al. Crit Care Med 2000;28:S81

SIRS with a presumed or

confirmed infectious

process

Step 3 what is sepsis?



Slide no: 12

• Sepsis with 1 sign of organ failure• Cardiovascular (refractory

hypotension)

• Renal

• Respiratory

• Hepatic

• Hematologic

• CNS

• Metabolic acidosis

SepsisSIRSInfection/Trauma

Severe Sepsis

Bone et al. Chest 1992;101:1644; Wheeler and Bernard. N Engl J Med 1999;340:207



Slide no: 13

Step 4: what is Severe Sepsis?

Sepsis with organ dysfunction, including shock:

CNS: Acutely altered mental statusGCS<11

CVS: Syst <5th precentiaor mean <65 mmHg

Need for vasoactive drug to maintain BP

Unexplained metabolic acidosis: Base deicit>5mEq/L

Resp: Pao2/FiO2<300 OR Paco2>65mmHg OR>50%FiO2need to maintain saturation>92%

Renal: Creatinine >2mg/dl

or UO <0.5 ml/kg/hr for 2 hrs

Hepatic: Bilirubin >4.0mg /dl ALT2 times upper limit for age

Bone marrow: Platelets <80,000mm3/l

Hypoperfusion: Lactate >above limits lab

Coagulopathy: INR>1.5 or aPTT >60secs



Slide no: 14

:Age specific upper and/lower limits of heart rate to define

tachycardia and bradycardia , respiratory rate, hypotension

Age group HR Mean(range)

RR(breath/min)

Systolic BP,mmHg

Upto1 month

140[100-190]

>60 <60mmHg

2months to 1 year

130[80-190] >50 <70mmHg

1-5 years 80[60-140] >40 <70+[2xage]

6-10 years 80[60-130] >30 <70+[2xage]

>10years 75[60-100] >30 <90

For heart rate lower values are approximately at 5th percentile and upper at 95

percentile for blood pressure, the heart rate values are at 5th percentile and for

respiratory rate the values are at95th percentile



Slide no: 15

What is Septic shock?

• Septic shock

• In a child with sepsis presence of : hypotension [ systolic BP< 70

mmHg in infant, <70+2 x age after 1 year of age ] or need for

vasoactive drug to maintain BP above fifth centile range

• or signs of hypoperfusion----any three of the following

• : decreased pulse volume [ weak or absent dorsalis pedis pulse] ,

• capillary refilling>2Sec

• , tachycardia heart rate as defined in [table] ,

• core [ rectal /oral ] to peripheral [skin –toe] temperature gap >3C ,

and

• urine output [<0.5ml/kg/h ] or sign of CVS dysfunction



Slide no: 16

Step 2: What counts as an infection?

RECOGNITATION: SCEERING FOR

INFECTION

i.e, if it sounds like an infection (history), or if

it looks like an infection (examination,

observations), then it probably is an infection!!



Slide no: 17

Step 2: What counts as an infection?

Pneumonia 50%

Urinary Tract infection

Meningitis

Endocarditis

Device related Central line

Cannula

• Abdominal 25%• Pain

• Diarrhoea

• Distension

• Urgent laparotomy

• Soft tissue/ musculoskeletal• Cellulitis

• Septic arthritis

• Fasciitis

• Wound infection



Slide no: 18

• Sepsis (documented or suspected infection plus ≥1 of the following)

• General Variables

• Fever.>38.3C

• Hypothermia(Core temperature <36C

• Heart rate > more than two SD above normal value for age

• Tachypnea

• Altered mental status

• Significant edema or positive fluid balance (>20ml/kg over 24 hr)

• Hyperglycaemia( plasma > 140mg/dl) in the absence of diabetes

• Inflammatory variables

• Leukocytosis (WBC count >12,000 mm3)

• Leukopenia( WBC count< 4000m3)

• Normal WBC count with >10% immature form

• Plasma C-reactive >two SD above normal value

• Plasma procalcitonin > TWO SD above normal

Diagnostic Criteria for Sepsis, Severe Sepsis, and

Septic Shock.



Slide no: 19

• Hemodynamic Variables

• Arterial hypotension SBP< 5TH Percentile or mean<65 mmHg

• Organ dysfunction Variables

• Arterial hypoxemia (Pao2/Fio2< 300)

• Acute oliguria (urine output <0.5ml/kg/hr for at least 2 hrs despite adequate

fluid resuscitation

• Creartinine increase >0.5mg/dl

• Coagulation abnormalities(INR >1.5 or aPT T>60s)

• Ileus

• Thrombocytopenia( platelet count <80,000mm3)

• Hperbilirubinemia (plasma total bilirubin >4mg/dl)

• Tissue perfusion variables

• Hyperlactaemia

• Decreased capillary refill or mottling skin

• Flash capillary refill

• Bounding peripheral pulses Warm Shock

• Wide pulse pressure(DPP< 1/3 of SBP)



Slide no: 20

Causes of organ failure

• Reduced delivery of oxygen to the tissues

• In sepsis, caused by any or all of:• Hypoxia

• Hypotension

• Low cardiac output

• Redistribution of blood flow

• Oedema- further for oxygen to travel to cells

• Small blood clots (microthrombi)

• Mitochondria don’t work effectively

We need to correct these with interventions... And FAST



Slide no: 21

Mortality increases with increasing

organ failure

Hebert et al. Chest 1993;104:230-5



Slide no: 22

• For first 12 hours, 1% mortality per 5 minute delay

• Funk and Kumar, Crit Care Clinics 2011; 53-76



Slide no: 23

Sepsis ManagementTime

Early diagnosis

Antibiotic administration

Hemodynamic stabilization

EGDT( A more definitive resuscitation strategy involves goal

oriented manipulation of cardiac preload ,after load and

contractility to achieve a balance between systemic oxygen

delivery and O2 demand River et al described steps

during the critical “GLODIN HOURS” (first 6 hours)

2012 Surviving Sepsis Campaign guidelines



Slide no: 24

N Engl J Med, Vol .354,No 19 November 2011

EGDT



Slide no: 25



Slide no: 26



Slide no: 27

Pre and post-discharge

Hospitalization

24 hours

6 hours

Recognition

Resuscitation

Initial Management

Maintenance

Recovery

RESUSCITATION

PHASE

GOAL: Keep him

alive for 24

hours

INITIAL

MANAGEMENT

PHASE

GOAL: Let’s get

him better

MAINTENANCE

PHASE

GOAL: Don’t kill

him



Slide no: 28

SEPSIS RESUSCTATION BUNDLE

• TO BE COMPLETWITHIN 3HOURS :

• Measure lactate level

• Obtain blood cultures prior to administration of antibiotics

• Administer broad sepectrum antibiotics

• Administer 20ml/kg crystalloid

• TO BE COMPLETED WITHIN 6 HOURS

• Apply vasopressors to maintain BP > 5th percentile for age

• In the event of persistent arterial hypotension despite volume

resuscitation:

• - Measure central venous pressure CVP>8mmHg

• - Measure central venous oxygen saturation(Scvo2)>70%

• Remeasure lactate if initial was elevated

• g



Slide no: 29

Goal-directed therapy hemodynamic

target in septic shock

• Capillary refill <2Sec

• Urine out put>1ml/kg/h

• Heart rate: age approporiate

• Arterial O2 Sat >95%

• ScvO2 >70%

• Difference in preductal and postductal O2 <5%

• MAP Age appropriate



Slide no: 30

MANAGEMENT

• Maintain or restore airway, oxygenation and ventilation{up

to 40% of CO is used for work of breathing}

• Maintain or restore circulation: normal perfusion and blood

pressure; maintain or restore threshold HR

• MONITORING

• Pulse oximeter, ECG, BP, Pulse pressure, DBP,

Temperature, urine output, glucose, ionized calcium



Slide no: 31

Airway

Breathing

Circulation

Disability

Exposure

Assessing any Critically Ill patient



Slide no: 32

Recognize decreased mental status and perfusion. Begin high flow O2.Establish IV/IO access

• INTIAL RESUSCITATION

Push boluses of 20cc/kg isotonic saline up&over 40cc/kg then 3rd subsequent bolus 0.5g/kg 5% albumin until perfusion improves or unless rales or hepatomegly develop.

Correct hypoglycaemia &hypocalcaemia . Begin antibiotics

• Shock not reversed: Fluid refractory shock Begin inotropes

0

min

15

min



Slide no: 33

becomes...



Slide no: 34

The Sepsis Six

1. Give high flow oxygen

2. IV fluid resuscitation

3. Give IV antibiotics

4. Take blood culture

5. Check haemoglobin and lactate

6. Accurate hourly urine output monitoring

may require catheter

... plus Critical Care support to complete EGDT

EARLY GOAL- DIRECTED THERAPY

Within one hour



Slide no: 35

Step 1: Oxygen

Oxygen delivery (DO2) is impaired

So, high flow oxygen maximises SaO2

‘Sats’ of 99% are better than 95% in sepsis!!

DO2 = CaO2 x CO

CaO2 = ([Hb] x SaO2)



Slide no: 36

Step 1: Is oxygen supply keeping up

with demand?

Central venous O2 saturation

Reflects oxygen extraction

by tissue, relative to

oxygen delivery

Lactate clearance

Reflects transition

from anaerobic to

aerobic metabolism

Oxygen delivery is determined by:

Hemoglobin

Cardiac output

Arterial oxygen saturation



Slide no: 37

HEART

ARTERIESVEINS

ORGANS

O2

O2

O2

O2

O2

O2

O2

O2

STEP 1: Make sure

the pump is full

(volume depletion)



Slide no: 38

Step 2: Fluids

Why?

To reduce organ dysfunction and multi-organ failure

• By optimising tissue oxygen delivery

• By increasing organ perfusion



Slide no: 39

Fluid resuscitation

In the first hour:

• Fluids improve Cardiac Output (CO)

• Better Cardiac Output gives

• Higher delivery of O2

• Higher MAP

• This will reduce organ injury



Slide no: 40

Improving organ perfusion

• Organs have their own resistance to blood flow

• Perfusion depends therefore on pressure as well as flow

• Mean arterial pressure (MAP) is the key

MAP = CO x SVRWhere SVR is Systemic Vascular Resistance

Goal MAP > 65 or Systolic > 5th percentile

MAP = Diastolic + (systolic-diastolic)

3

An improved cardiac output gives a higher MAP



Slide no: 41

The C in the ABCs:

Volume ResuscitationAssess for Volume Depletion

•History

•Exam - Organ perfusion – skin, brain, kidneys

•Measure intravascular pressures – arterial, central venous

Administer a “Fluid Challenge”

•20ml/kg cry stolid over 5-10 minutes up to over

60ml/kg until perfusion improves

Normalization of the heart rate•Capillary refill of < 2sec•Well felt dorsalis pedis pulses with no differential between peripheral and central pulses•Warm extremities•Normal of systolic pressure and pulse pressure•Urine output> 1 ml/kg/hour•Return to baseline mental status tone and posture•Normal range respiratory rate



Slide no: 42

HEART

ARTERIESVEINS

ORGANS

O2

O2

O2

O2

O2

O2

O2

O2

STEP 2: Make the train is on

a fast track (vascular tone)

STEP 1: Make sure

the pump is full

(volume depletion)

STEP 3: See if supply is

keeping up with demand



Slide no: 43

How to fluid resuscitate

Judicious fluid challenges

• Up to 60ml/kg in divided boluses (min. 20ml/kg in shock)

Reassess for effect after each challenge

• HR, BP, capillary refill, urine output, RR

In patients with cardiac disease

• Use smaller volumes

• More frequent assessment

• Early CVC



Slide no: 44

Before starting antibiotics, take at least one blood culture:

• Percutaneously

• AND at least one from each vascular access device (if > 48 hrs)

Other cultures:

• Urine

• CSF

• Faeces

• Wound swabs

• Sputum

• other fluids from within cavities, e.g, intraperitoneal

Step 3: Blood Cultures



Slide no: 45

Within 6 hours source must be controlled

With cultures, consider:

Diagnostic imaging X ray

USS

CT

MRI

Discuss with radiologist/ surgeon if an enclosed

collection suspected

Step 3b: Source Control



Slide no: 46

Guidelines for obtaining cultures before

starting antibiotics

• Obtain two or more sets of BCs (both aerobic and anaerobic

bottles)

• One or more BCs should be Percutaneously

• One BC from each Vascular access device in place > 48hrs

• Culture other sites as clinically indicated (eg, urine, wound,

sputum, faecal, bronchial aspirate, CSF)



Slide no: 47

Start therapy as soon as possible and certainly in the first

hour...

...preferably after taking blood cultures!!

Choice should include one or more with activity against likely

pathogen

• Penetration of presumed source

• Guided by local pathogens

• Give broad spectrum till defined

Step 4: Give Antibiotics



Slide no: 48

• Antimicrobial regimen should be reassessed daily for potential de-

escalationto the most appropriate single therapy should be

performed as soon as the susceptibility profile is known .

• . Duration of therapy typically 7–10 days; longer courses may be

appropriate in patients who have a slow clinical response,

• Use of low procalcitonin levels or similar biomarkers to assist

the clinician in the discontinuation of empiric antibiotics in

patients who initially appeared septic, but have no subsequent

evidence of infection

• For patients with severe infections associated with respiratory failure

and septic shock, combination therapy with an extended spectrum

beta-lactam and either an aminoglycoside or a fluoroquinolone is for

P. aeruginosa bacteremia

• A combination of beta-lactam and macrolide for patients with septic

shock from bacteremic Streptococcus pneumoniae infections



Slide no: 49

Evidence!!

Cohort size Mortality % RRR %

(NNT)

Total 567 (100%) 34.7 -

No fluids in 1h 183 (32.3%) 44.8

Fluids in 1h 384 (67.7%) 30.0 33.0

(6.73)

© Ron Daniels 2010 Reproduction in part or whole not permitted



Slide no: 50

Evidence: fluids and antibiotics together

Cohort size Mortality % RRR %

(NNT)

Total 567 (100%) 34.7 -

Neither fluids

nor antibiotics

in 1hr

170 (30.0%) 45.3

Antibiotics after

BC and fluids

238 (42.0%) 24.0 47.0

(4.69)

© Ron Daniels 2010 Reproduction in part or whole not permitted



Slide no: 51

High lactate identifies tissue hypoperfusion in

patients at risk who have a normal BP

‘Cryptic shock’

Gives an overview of current tissue oxygen delivery

The Goal

Lactate to improve

as resuscitation

progresses

Step 5: Measure lactate



Slide no: 52

Risk stratification by lactate

0

5

10

15

20

25

30

35

40

% in

ho

sp

ita

l M

ort

alit

y

Lactate threshold

Low (0 - 2.0)

Intermediate ( 2.1 - 3.9)

Severe (>4.0)

Trzeciak, S et al , Acad Emerg Med; 13, 1150-1151.



Slide no: 53

STEP 6: Urine Output

Urine output is a direct measure of GFRGFR= Glomerular Filtration Rate

GFR is directly proportional to COKidneys receive 1/5 cardiac output (1 L/min)

CO falls UO falls

Therefore urine output in the early stages is a useful assessment of cardiac output



Slide no: 54



Slide no: 55

Renal Blood Flow & Urine Output

In health, kidneys

autoregulate, so UO is

independent of BP over

a wide range

In sepsis, this is lost and

UO will fall as BP falls



Slide no: 56

Effects of fluid resuscitation

So…

Fluid resuscitation can improve

• Cardiac output (raises)

• Blood pressure (raises)

• Haematocrit (lowers)

… each of which will improve urine output



Slide no: 57

Goals for the first hour

Evidence of success:

•MAP >65mmHg

• Improving capillary refill

•Warming of extremities

•Urine output >1 ml/kg/hr

• Improving mental status

•Decreasing lactate



Slide no: 58

Pre and post-discharge

Hospitalization

24 hours

6 hours

Recognition

Resuscitation

Initial Management

Maintenance

Recovery

RESUSCITATION

PHASE

GOAL: Keep him

alive for 24

hours

INITIAL

MANAGEMENT

PHASE

GOAL: Let’s get

him better

MAINTENANCE

PHASE

GOAL: Don’t kill

him



Slide no: 59

INITIAL MANAGEMENT PHASE

GOAL: Let’s get him better

• Supportive care

• Identify organ failures

• Customize antibiotics based on

cultures/sensitivities

• Additional diagnostic testing

• Inotropes/Vasopressors/Vasodila

tors

• Corticosteroids

• Blood Products and plasma

Therapies

• Specific care

• Lung protective ventilation

• Conservative fluid management

• Sedation/Anlagesia/drug

Toxicities

• Glycemic control

• Deep Vein Thrombosis

Prophylaxis

• Stress Ulcer Prophylaxis

• Nutrition :enteral and iv glucose



Slide no: 60

Hydrocortisone Therapy

a child is at risk of absolute adrenal insufficiency or adrenal pituitary

axis failure (e.g., purpura fulminans, congenital adrenal hyperplasia,

prior recent steroid exposure, hypothalamic/pituitary abnormality)

and remains in shock despite epinephrine or norepinephrine

infusion,

• then hydrocortisone can be administered ideally after attaining a

blood sample for determination of baseline cortisol concentration.

Hydrocortisone may be administered as an intermittent

• or continuous infusion at a dosage which

• may range from 1–2 mg/kg/day for stress

• coverage to 50 mg/kg/day titrated to reverse the shock



Slide no: 61

Persistent Pulmonary Artery Hypertension

• Inhaled NO therapy is the treatment of choice for uncomplicated

PPHN However,

• metabolic alkalinization remains an important initial resuscitative

strategy during

• shock because PPHN can reverse when acidosis

• Milrinone or inamrinone may be added to improve heart function as

tolerated

• ECMO remains the therapy of choice for patients with refractory

• PPHN and sepsis

• New investigations:

• support use of inhaled iloprost (synthetic analog of prostacyclin) or

adenosine infusion as modes of therapy for PPHN



Slide no: 62

MAINTENANCE PHASEGOAL: Don’t kill him

• Avoid nosocomial

complications

• Ventilator-induced lung

injury

• Get tubes and lines out

of him

• Clots and bleeding

• Avoid new infection

• Hand washing

• Semi-recumbent position

• Get tubes and lines out of

him

• Minimize transfusions



Slide no: 63

Long-term Cognitive Impairment and Functional Disability

Among Survivors of Severe Sepsis

• Compared 516 severe sepsis survivors with 4517 survivors of non-

sepsis hospitalization

• Prevalence of mod/severe cognitive impairment increased by 10.6%

after sepsis

• Severe sepsis associated with development of 1.5 new limitations in

ADLs

• 59% of sepsis survivors had worsened cognitive and/or physical

function Long-term Cognitive Impairment and Functional Disability

Among Survivors of Severe Sepsis

• Significantly worse than for non-sepsis hospitalizations

Iwashyna et al. JAMA 2010;304(16):1787-94



Slide no: 64

What is it?

•SIRS + Infection = Sepsis

•Sepsis + Organ Failure = Severe Sepsis

•Sepsis + Shock = Septic Shock

•Mortality increases with more organ failure

•GOLDEN HOURS \definitive recognition and

treatment provide maximal benefit in term of outcome



Slide no: 65

Mangement of sepsis and septic shock

Health & Medicine

Transcript of Mangement of sepsis and septic shock