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10 million death
50 million per year
Number 1 cause of death
Surviving Sepsis Campaign: International
Guidelines for Management of Sepsis and
Septic Shock new OCT 2021 version
Management of Septic Shock

Objectives:
• To distinguish the different categories of
shock
• To understand the pathophysiology of
shock
• To recognize the early diagnosis and
treatment of shock and multiple organ
failure (MOF)
• To identify the prevention of shock or MOF
 Multiple organ failure

Circulatory failure

Criteria for diagnosis

Bradycardia (heart rate <50 bpm)
Hypotension (mean arterial pressure <50
mmHg)
Ventricular tachycardia or fibrillation
Metabolic acidosis (pH <7.2)

Management
Optimise cardiac preload
Maximise cardiac contractility with inotropes
Maximise perfusion pressures with vasopressors
Correct anaemia
Treat arrhythmia
Haematological failure Gastrointestinal failure
Criteria for diagnosis Criteria for diagnosis
Leucopenia (WCC < 1000 cell / mm3) Ileus
Thrombocytopenia (PLT < 20,000 / mm3) Gastroparesis
Evidence of DIC Haemorrhage
Management Management
Red cell and platelet transfusion Parenteral nutrition
Fresh frozen plasma Stress ulcer prophylaxis
Correct antithrombin III deficiency Selective gastrointestinal decontamination

Hepatic failure Neurological failure

Criteria for diagnosis Criteria for diagnosis
Coagulation defect Depressed level of consciousness (GCS <6)
Rising hepatic enzymes AST/ALT Fits
Management Management
Fresh frozen plasma Oxygenation
Nutritional support Control seizures
Correct hypoalbuminaemia
Renal failure in Kam Shui  Stage of CKD
ARDS… PaO2/FiO2 Ratio
Shock: Definition & causes

• The clinical syndrome that occurs

when acute circulatory failure with
inadequate or inappropriately
distributed tissue perfusion
results in failure to meet tissue
metabolic demands causing
generalized cellular hypoxia

What is released…
Shock can be classified into
6 categories

• Hypovolaemic shock: > 15% volume

– Due to major reduction in circulating blood
volume caused by haemorrhage, plasma
loss (e.g. burn, pancreatitis or extracellular
fluid loss or trauma)

• Cardiogenic shock:
– Due to severe heart failure (e.g. MI, acute
mitral regurgitation)
Shock can be classified into
6 categories

• Anaphylactic shock:
– Due to allergen-induced vasodilatation (e.g.
bee sting, peanut & other food allergies)

• Neurogenic shock:
– Follows high traumatic spinal cord lesions
– Interruption of sympathetic outflow causes
vasodilation, hypothermia & bradycardia
Shock can be classified into
6 categories

• Obstructive shock:
– Caused by circulatory obstruction (e.g.
pulmonary embolism, cardiac tamponade 心臟
壓塞)

• Septic shock
Defining sepsis

Neutropenia in chemotherapy!
Sepsis in Adult
Sepsis is a syndrome comprising an immune
system-mediated collection of physiological
responses to an infectious agent. Clinical
signs such as fever, tachycardia, and
hypotension are common but the clinical
course depends on the type and resistance
profile of infectious organism, the site and
size of the infecting insult, and the genetically
determined or acquired properties of the
host's immune system.
Cellular Effects of Shock
Initial Inflammatory response

• The presence of an abnormally large blood supply in

which the blood vessels are dilated and the flow of blood
is lower
• Increased permeability in the smaller blood vessels,
allowing the body to position blood elements in the area in
order to heal the injured tissue or combat any introduced
foreign agents
• The movement of fluid and blood cellular elements
(exudates) into the injured tissue
• Accumulation of fluids within the tissue(s) that then slows
or stagnates blood flow
Inflammatory response

• In the normal inflammatory response, the

damage that occurs to the endothelium of
the microcirculation enables fluid to leak
out and activates the clotting cascade
• The formation of clots are essential to
prevent debris from macrophage action
and invading pathogens entering the
systemic circulation
• At the appropriate time, the clot is
dissolved and blood flow is restored
Benefits of normal inflammatory
response

• The increased fluid dilutes the irritants

• The blood cells engulf and often digest bacteria,

dead cells, or other debris that might cause or
continue the inflammation

• antibodies, which are also present in the edema

fluid, neutralize toxic substances

• Clotting of the edema fluid walls off the area and

prevents the irritant and the inflammation or the
inflammatory process from spreading beyond the
affected site
SEVERE SEPSIS OCCURS

When inflammatory response no longer localized at the

affected site, but spreading to systemic circulation
qSOFA  machine learning

7 mmol/L
SOFA
Septic shock: 50% mortality
• The early symptoms of systemic vasodilatation
can be observed firstly in septic shock
• The release of inflammatory mediators results in
an increase in peripheral circulation and
permeability of the micro-vascular circulating
system creating a loss of volume in blood
circulation
• Decrease systemic blood volume leading to
hypoperfusion
• The consequence of this is the derange of organ
functioning due to a reduction of O2 supply to
cells, resulting from hypoperfusion
Clinical Features of Sepsis

 Hypotension – MAP < 65 and SBP < 90 mmHg

 Tachycardia – HR > 100 beats / min
 cardiac output
 Rapid respiration – RR > 25 / min
 Cells hypoxia  produce lactate (acid)  reduction
of PH 2mmol/L
 Excite medulla oblongata to stimulate respiration
 Oliguria – urine output 0.5 mL/kg/hr, < 30 ml / hour
  renal perfusion
 Drowsiness, confusion or agitation
 cerebral perfusion
Early presentation symptoms

 ↑ in respiratory rate
 Hypoperfusion (vasodilatation)
 Reduction in O2 supply to cells
 Cellular hypoxia
 Change in acid base balance
 Excite medulla oblongata
 Appear red and flushed
 Full & bounding pulse
 Rapid capillary refill
Other presentation symptoms

 ↑ HR
 Altered mental state
 ↓ urine output
 Due to ↓ venous return and stroke
volume
 An initial ↑ in diastolic pressure, then
drop in BP and alteration in
temperature are late symptoms
PCT: Procalcitonin Vs CRP (Davis & Lockhart, 2014)
 Weak

recommend
As Stroke and Trauma: < 1 hr
Thompson et al., 2019
Haemodynamic support
• In early sepsis: widespread vasodilation
causes hypotension and relative
hypovolaemia. Reduced left ventricular
afterload increases cardiac output but
inappropriate distribution can cause
regional ischaemia.
• In late sepsis: toxic myocarditis impairs
myocardial contractility and reduces
cardiac output.
 Prevention of sepsis
 Removal of invasive intravenous and urinary catheters that
are no longer needed
 Employing a non-touch technique in wound dressing will help
to reduce the complications that can result in sepsis
 Early mobilization reduces the risk of hydrostatic pneumonia
and improves circulation
 If mobilization is not possible, optimizing respiratory function
with the incentive spirometry and physiotherapy will help
 Maintaining hydration and nutrition are effective to limit the
risk of sepsis
 Implement modified early warning systems (MEWS) to detect
early signs and symptoms of patient deterioration
 Where prevention fail, early interventions is imperative in
prevention deterioration
Sepsis 6 treatment pathway

 Oxygen therapy: SaO2 > 94%

 Fluid resuscitation: 500 ml (5-30 min)
then 1.5 - 2L max to review
 Inotrope and vasoactive support
 Measurement and monitoring of urine
output:
 Blood cultures
 Antimicrobial treatment IVI within 1 hr
 Lactate, hemoglobin and routine blood
monitoring
Sepsis 6 treatment pathway

 Oxygen therapy: SaO2 > 94%

 Fluid resuscitation: 500 ml (5-30 min) then 1.5 -
2L max to review
 Inotrope and vasoactive support: noradrenaline
 Measurement and monitoring of urine output: 0.5
ml/kg/hr
 Blood cultures, CSF, urine, sputum… Sepsis
work-up before antibiotics + MRSA coverage
(2021) + optimizing dosing
 Antimicrobial treatment IVI within 1 hr + infusion
 Lactate > 4 mmol/L, hemoglobin and routine
blood monitoring Glucose < 10 mmol/L
Oxygen therapy

• High dose via a non-rebreathing mask

• Use of high flow nasal oxygen (also
known as HFNC) over noninvasive
ventilation (NIV) (new, low quality)
• If patients with altered mental status,
respiratory distress or severe
hypotension, elective intubation and
mechanical ventilation should be
considered
Fluid resuscitation

• We recommend that in the resuscitation from

sepsis-induced hypoperfusion, at least
30ml/kg of intravenous crystalloid fluid be
given within the first 3 hours.

• Crystalloid and albumin when patients require

substantial amount…

• Frequent re-assessment of hemodynamic

status
Fluid resuscitation and
central venous pressure monitoring
• CVP: 8-12 mmHg (more fluid as usual) 10 cm H2O

• Mean arterial pressure (MAP) ≧ 65 mmHg

• Urine output ≧ 0.5 ml/kg h-1

• Central Venous oxygen saturation SCVO2 ≧70%

• In ventilated patients, a higher CVP target of 12 – 15

cm H2O is recommended (reflect the changes in
intrathoracic pressure resulting from +ve pressure
ventilation)
Passive Leg Raising
Inotrope and vasoactive support

• The use of a systemic vasopressors is

indicated to restore blood flow to
pressure-dependent vascular beds (heart
& brain)
• Norepinephrine (Noradrenaline in HK)
should be used as first line treatment, no
evidence suggests the use of one over the
other (2021)  Dopamine  Vasopressin
• Norepinephrine: 2 mg in 50mL D5 in NTEC
Blood culture

• Obtained before antibiotic therapy

• At least 2 cultures should be obtained
• 1 drawn percutaneously and 1 drawn
through each vascular access device,
unless the device was recently
inserted (< 48 hours)
• 1 from central venous access (if any)
Antibiotic therapy ASAP 
• Stated within the first hour of recognition of
both sepsis and septic shock 
• Empiric broad-spectrum therapy 1+1 
• Patient’s history (including drug tolerance),
underlying disease, the clinical syndrome
and susceptibility patterns of 
microorganisms (potentially fungal or viral
origin)
• MRSA coverage (2021)
• Emergency source control* (2021)
Lactate measurement

• At a Lactate level of ≧ 4 mmol/L,

commence treatment
(watch out if Lactate > 2 mmol/L)
• Indicator for the need to start treating
the patient with sepsis
IL-6, IL-8, IL-1Beta, TNF & IL-33 in Southampton COVID-19 study
The 24 hour care bundle

Glucose control

Reduce level to 8 to 10 mmol/L (insulin)

Corticosteroids
fluid resuscitation & vasoactive support has
been poor e.g. Hydrocortisone 200 mg/day
Adrenal
Lung protective strategies
Lung protective strategies

• Reduction in tidal volume to 6 ml/kg body

weight (normal: 8-10mL/kg) 
– Higher PEEP if necessary
• Plateau pressure < 30 cmH2O 
• Ventilated patients the head of the bed
should be elevated to 30-45。
• Positioned prone (patients with sepsis-induced ARDS
and a PaO2/FIO2 ratio <150.) or HFOV 
• Against use of Beta-2 agonist without
bronchospasm
Weaning protocol

• Breathing trial
• Targeted sedation scoring
• Restrict use of paralyzing agents
• Early extubation
• Early tracheostomy for failed
extubation
References
Davis, C. & Lockhart, L. (2014). Get to know the international sepsis guidelines.
Nursing Incredibly Made Easy, 12(1), 41-50.
Leach, R. (2009). Acute and critical care medicine at a glance (2nd Ed.). Oxford:
Wiley-Blackwell.
http://www.survivingsepsis.org/SiteCollectionDocuments/Bundle-Six-Hour-
Step1_Vasopressors.pdf
Multiple Organ Dysfunction Syndrome in Sepsis in Medscape
Assessing, managing and treating patients with sepsis
Bacterial Sepsis from: http://emedicine.medscape.com/article/234587-
medication#showall
Makic MBF, Bridges E Managing sepsis and septic shock: current guidelines
and definitions Am J Nurs 2018 118 2 34 9
Surviving Sepsis Campaign: International Guidelines for Management of Sepsis
and Septic Shock: 2016
Best Practice BMJ: http://bestpractice.bmj.com/best-
practice/monograph/245/treatment/step-by-step.html
Thompson, K., Venkatesh, B., &amp; Finfer, S. (2019, February 12). Sepsis and
septic shock: Current approaches to management. Retrieved October 08, 2020,
 Care of the relatives in 2021

For adults with sepsis or septic shock

- discuss goals of care and prognosis with patients
and families over no such discussion
- Include principles of palliative care (consultation
based on judgement) be integrated into the
treatment plan to address family symptoms and
suffering
- Include information about ICU stay, sepsis,
diagnoses, RX and impairments after sepsis in
verbal and written hospital discharge summary
- + discharge plan / follow up on cognitive, physical
and emotional problems on discharge
Evans et al., 2021
Time ZERO & Hour-1 Surviving Sepsis
Bundle of Care
Sepsis in COVID-19
Antibiotics

Imipenem-cilastatin Tienam
Meropenem Carbapenem
Piperacillin Tazobactam
Tazocin Levoloxacin
Metronidazole Maxipime
Augmentin Vacomycin
Aztreonam (-) Linezolid (+)
Ceftriaxone Tigecycline
“We recommend that hospitals
and hospital systems have a
performance improvement program
for sepsis including sepsis
screening for acutely ill, high-risk
patients.”