This document discusses shock, specifically endotoxic shock. It begins with definitions of terms like shock, sepsis, and systemic inflammatory response syndrome. It then classifies and describes the different types of shock: hypovolaemic, distributive, obstructive, and cardiogenic. The main focus is on the pathophysiology and management of septic shock. It discusses the circulatory dysfunction that occurs in sepsis and leads to shock. The clinical features, evaluation, and treatment principles including hemodynamic support, fluids, vasopressors, inotropes, antimicrobial therapy, and surgery are covered. Prevention and prognosis of septic shock are also mentioned.

1. Define and classify shock. Discuss
the current concepts in the
pathophysiology and management
of endotoxic shock
Dr Eretare C. Odjugo

2.  Introduction
 Definition of terms
 Classification of shock
 Bacteriology
 Aetiology of septic shock
 Pathophysiology of septic shock
 Clinical features of septic shock
 Evaluation
Outline

3.  Treatment of septic shock
 Prognosis
 Prevention
 Conclusion
 References
Outline

4.  Infections are a continuous challenge in medical
practice especially in resource limited areas
 The extent of the infection is affected by the persons
co-morbidities, virulence of the infective organism,
hosts immune response and other factors.
Introduction

6.  Infection: An infection is the invasion of an organism's
body tissues by disease-causing agents, their
multiplication, and the reaction of host tissues to the
infectious agents and the toxins they produce.
 Shock: A state of cellular and tissue hypoxia due to
either reduced oxygen delivery, increased
consumption, inadequate oxygen utilisation or a
combination of these processes.
Terminology

7.  Sepsis is defined as life-threatening organ dysfunction
due to dysregulated host response to infection.
 Organ dysfunction is defined as an acute change in
total Sequential Organ Failure Assessment (SOFA)
score of 2 points or greater secondary to the infection
cause.
Terminology

8.  Systemic Inflammatory Response Syndrome (SIRS):
 Adult: Manifestations of SIRS include, but are not limited to:
 Body temperature <36 °C or >38 °C
 Heart rate >90 beats per minute
 Tachypnea (high respiratory rate), with >20 breaths per
minute; or, an arterial PaCO2 less than 4.3 kPa (32 mmHg)
 White blood cell count <4 x 109 cells/L or >12 x 109 cells/L; or
the presence of >10% immature neutrophils (band forms).
Band forms >3% is called bandemia or a "left-shift.”
Terminology

9.  In children
 Heart rate >2 SD above normal for age in the absence of
stimuli such as pain and drug administration, or unexplained
persistent elevation for >30 minutes to 4 hours.
 Body temperature obtained orally, rectally, <36 °C or >38.5 °C.
 Respiratory rate >2 SD above normal for age or the
requirement for mechanical ventilation not related to
neuromuscular disease or the administration of anesthesia.
 White blood cell count elevated or depressed for age not
related to chemotherapy, or >10% bands plus other immature
forms.
Terminology

10.  Septic shock: Septic shock is defined by persisting
hypotension requiring vasopressors to maintain a
mean arterial pressure of 65 mm Hg or higher and a
serum lactate level greater than 2 mmol/L (18 mg/dL)
despite adequate volume resuscitation
Terminology

13. Aetiology

14.  Hypovolaemic
 Distributive
 Obstructive
 Cardiogenic
Classification of shock

15.  From loss of blood volume or plasma
 Seen in major bleeding, trauma and burns
 Characterised by
 tachycardia,
 cool clammy extremities,
 hypotension,
 dry skin and mucous membranes, and
 poor turgor.
Hypovolaemic shock

16.  Caused by an extrinsic or intrinsic impedance to
circulation
 Pulmonary embolism
 Cardiac tamponade
Obstructive shock

17.  Caused by primary myocardial dysfunction despite
normal intravascular volume.
 Normal cardiac output not maintained
 Characterised by
 cool clammy extremities,
 poor capillary refill,
 tachycardia,
 a narrow pulse pressure, and
 low urine output.
Cardiogenic shock

18.  Excessive vasodilation
 Impaired blood flow
 Reduced vasomotor resistance or increased
capacitance
 It’s characterised by
 high cardiac output,
 hypotension,
 a large pulse pressure,
 a low diastolic pressure, and
 warm extremities with good capillary refill
Distributive shock

19.  Septic shock
 Anaphylactic shock
 Neurogenic shock
Distributive shock

20. Bacteriology

21.  The normal physiologic response to localized
infection includes activation of host defence
mechanisms that result in the
 influx of activated neutrophils and monocytes,
 release of inflammatory mediators,
 local vasodilation,
 increased endothelial permeability, and
 activation of coagulation pathways.
Pathophysiology

22.  These responses are brought about by the interaction
between the host responses and the infective agent
 In sepsis, there is an exaggeration of these host
responses.
 leading to
 diffuse endothelial disruption,
 vascular permeability,
 vasodilation, and
 thrombosis of end-organ capillaries
Pathophysiology

23.  In Gram negative bacteria, the Lipid A moiety of the
lipopolysaccharide molecule leads to cytokine
induction via the lipoteichoic acid.
 For Gram positive bacteria they may also bring about
production of cytokines by secretion of super-
antigens.
Pathophysiology

26. Sepsis induced ARDS

27. Septic encephalopathy

28. Sepsis induced coagulopathy

29.  This is the system responsible for the progression too
septic shock
 The main components are the vascular response
 Arteriolar vasodilatation
 Increased capacitance
 And Myocardial activity
 Chronotrophic
 Ionotrophic
Circulatory dysfunction in sepsis

30. Circulatory dysfunction in sepsis

31.  The hypotension is initially compensated by an
increased cardiac output but over time this also fails.
 Myocardial suppression is brought about by
 Beta adrenergic receptor downregulation
 Nitric oxide
 Pulmonary hypertension
Circulatory dysfunction in sepsis

32.  There is also a challenge with oxygen utilisation at
tissues
 Mitochondrial dysfunction which leads to anaerobic
respiration with resultant lactate production
 Diminished offloading at the tissues
 There is loss of the normal auto-regulatory function of
the autonomic nervous system and thus vital organs
(brain and heart) which normally receive preference do
not
Circulatory dysfunction in sepsis

33.  Major site of bacteria
 Hypoperfusion leads to failure of gut mucosal barrier
 Translocation of bacteria and endotoxin
 Propagation of sepsis
 Sepsis also causes ileus
GI dysfunction

34.  Hypoxic hypoxia: Decrease oxygen supply
 Histotoxic hypoxia
 Apoptosis
 Coagulopathy
 Immunosuppression
Organ dysfunction in sepsis

36. Clinical features
 Temperature abnormalities (fever or hypothermia)
 Elevated pulse rate with warm or cold extremities
 Altered mental status
 Dyspnoea
 Malaise and lethargy
 Localizing symptoms referable to organ systems may
provide useful clues to the etiology of sepsis.

37.  Full blood count (Leukocytosis with left shift)
 Blood culture (not always positive)
 Serum electrolytes, urea and creatinine
 Liver function test including total protein and albumin
 Clotting profile
 Serum lactate (assessment of perfusion)
 Blood glucose monitoring (predictor of mortality)
 Urinalysis and urine culture
Evaluation

38.  Specialised investigations to confirm source of
infection
 CT scans/MRIs of various regions
 Plain radiographs
 Ultrasound scans
Evaluation

39. SOFA scoring

40.  Based on the current literature, include the following:
 Early recognition
 Source control
 Early and adequate antibiotic therapy
 Early hemodynamic resuscitation and continued
support
 Proper ventilator management with low tidal volume
in patients with acute respiratory distress syndrome
(ARDS)
Management principles

41.  Resuscitation
 Venous access
 Fluids (Iso-osmotic crystalloids) 20 -40ml/kg over the first hour.
 Respiratory and ventilator support
 Urethral catheterisation
 Correction of anaemia
 Circulatory support
 Antimicrobial therapy
 Source control
 Temperature control
 Nutritional support
Treatment

42. Haemodynamic support
Aim for MAP >65mmHg
 Fluid
 Crystalloids
 Colloids (4% Albumin)
 Must be monitored for
overload
 Vasopressors
 Norepinephrine
 Epinephrine
 Dopamine
 Phenylephrine
 Ionotropes
 Dopexamine
 Dopamine
 Dobutamine

43.  Crystalloids ( 30ml/kg over 1st hour)
 Normal saline
 Ringers lactate (not preferred due to interaction with
lactate assays)
 Colloids
 4% Albumin: as effective as normal saline at less volume
more expensive
 Not readily available
Fluids

44. Vasopressor
First line
 Dopamine 5 – 10mcg/kg/min
 Tachyarhythmias
 May be increased to
20mcg/kg/min
 Norepinephrine 5 – 20mcg/min
 Not weight dependent
 Predictable response
 Shorter hospital stay with less
mortality
 Alpha agonist thus potent
vasoconstrictors
 0.2 – 1.5mcg/kg/min

45.  Second line
 Synthetic Human Angiotensin 2 (25ml/kg) improves response
when used with 1st line
 Epinephrine potent inotrope
 Causes myocardial and splanchnic ischemia
 Phenylephrine
 Selective potent vasopressor
 Causes reduce myocardial contractility and rate
 ADH
 Reserved for salvage therapy thus should not be used alone
 More potent when acting with nor epinephrine
Vasopressors

46.  Dobutamine:
 Recommended only when there is hypoperfusion
despite fluid targets and MAP targets have been met.
 Given at 20mcg/kg/min
 Dopamine
Inotropes

47.  Initial therapy should be combination broad spectrum for
suspected causative agents.
 Daily evaluation for effectiveness
 De-escalation to monotherapy later.
 An aminoglycoside (e.g gentamicin) should be used for
“antibiotic-experienced” patients.
 Cephamycins (Cefotetan) and Carbapenems are preferred for
ESBL producing bacteria (Kliebsiella and E. coli)
 Immunocompromised patients should receive carbapenems
or 4th gen Cephalosporins)
Anti-microbial therapy

48.  Intra-abdominal infection
 Antibacterials
 Metronidazole – Meropenem
 Imipenem – Cilastin
 Levofloxacin or Ciprofloxacin
 Piperacilin or Tazobactam
 Ceftazidim or Cefepime
 Antifungals
 Caspofungin
 Micafungin
 Fluconazole in C. albicans
Antimicrobial therapy

49.  The American College of Critical Care Medicine
recommends
 Avoidance of ACTH suppression test
 Use of Hydrocortisone as first line
 Use in patients with suspected adrenal insufficiency
 Do not use dexamethasone therapy for septic shock or
ARDS
 Treatment of septic shock
 200 mg/day in 4 divided doses or
 100mg bolus then 10mg/hour.
 If given for >14 days, it should be tapered off
Corticosteroid use

50.  Target is between 80 - 110 mg/dl (4.4 – 6.1mmol/l)
 Hyperglycaemia confers a 10% rise in mortality.
Glycaemic control

51.  In absence of bleeding
 Unfractionated heparin
 LMW heparin can be used.
 Dalteparin used in severe renal dysfunction CrCl
<30ml/min
 Compression stockings and intermittent compression
devices may be used.
DVT prophylaxis

52.  Treat underlying cause
 Transfuse with plasma or platelet concentrate
 Don’t treat prophylactically
DIC

53. Treatment of ARDS
 Intubation and
mechanical ventilation
 5 – 8 l/min
 Use of PEEP to prevent
lung injury
 Extra-corporeal
Membrane Oxygenation

54.  Ubi pus, ibi evacua.
 Antibiotic therapy alone may not suffice for some
causes of septic shock
 The source of infection should be controlled if not all
therapies will eventually fail.
 Abscesses should be drained either percutaneously or
an open drainage.
 Necrotic tissue should be debrided.
Surgery

55.  Renal dysfunction (AKI) may require dialysis
 For hepatic dysfunction, therapy is mostly supportive
Other modalities

57.  In the past decades, recovery and survival from septic
shock is on the rise.
 Some countries have as high as 50% (Australia) while
others 30% most developed countries.
 In our setting, septic shock is almost invariably fatal
due to challenges with finance, resources and
personnel.
Prognosis

58.  Basic measures to prevent nosocomial infections
include the following
 Shortening the hospital stay
 Removing indwelling catheters as early as possible
 Avoiding unnecessary invasive procedures
 Using aseptic techniques
 Prophylactic antibiotics for GI surgeries are also of
benefit
Prevention

59.  Sepsis and septic shock are major contributors to
surgical morbidity and mortality
 Early recognition and intervention are key to
improving outcomes.
 The best form of treatment still remains prevention
by eliminating risk factors as much as possible
Conclusion

60.  https://jamanetwork.com/journals/jama/article-
abstract/2598892 accessed last 3/8/20.
 https://emedicine.medscape.com/article/168402-
overview#a1 accessed on 4/8/20
 Surviving Sepsis: Guidelines for management of sepsis and
septic shock 2012
 https://www.uptodate.com/contents/definition-
classification-etiology-and-pathophysiology-of-shock-in-
adults accessed 03/08/20
 Images obtained from https://www.bing.com and are the
properties of the respective copyright holders
References

61. Thank you