1. Endotoxic shock is caused by bacterial endotoxins from gram-negative organisms leading to circulatory failure and organ dysfunction. 2. Pathophysiology involves vasodilation, increased capillary permeability, release of inflammatory mediators, and ultimately hypotension and multiple organ damage. 3. Management focuses on early goal-directed resuscitation including intravenous fluids, vasopressors, antibiotics, and source control to improve perfusion and prevent progression to irreversible shock.

1. Endotoxic shock in Pregnancy
Dr Shivamurthy H M
Prof in OBG
SNMC . BAGALKOT.
KARNATAKA . INDIA

2. Definition:
• Shock is defined as a state of circulatory inadequacy with
poor tissue perfusion resulting in generalized cellular
hypoxia.
• Circulatory inadequacy is due to a disparity between the
circulating blood volume and the capacity of the circulatory
bed.
• The net effect of this disparity is inadequate exchange of
oxygen and carbon dioxide between the intraand
extravascular compartments.
• The stagnation of carbon dioxide and other metabolites in
the tissue leads to metabolic acidosis and cellular death.

3. The series of changes observed in shock
The series of changes in shock and their clinical
manifestations dependent on two sets of changes:
(a) Circulatory inadequacy at the ‘ filtration ’
level (microvascular compartment)
(b) Cellular damage and ultimately death.

4. Anatomy of microvascular circulation
• Microvascular circulation consists of circulation
of blood through a tuft of capillaries with a
feeding arteriole and a draining venule at either
end of the capillary bed.
• The flow of blood within the capillary bed is
controlled by 2 sphincters – one at the arteriolar
end and the other at the venular end.
• They are known as pre- and postcapillary
sphincters In addition to the tuft of capillaries,
there is a direct communication between the
arteriole and the venule and this communicating
trunk bypasses the capillary bed.
• This is known as metarteriole shunt or
‘ thoroughfare channel ’.
• When the sphincters are closed, the metarteriole
shunt operates to divert blood for supply to the
vital organs, like brain, heart and kidney.

5. Pathophysiology of Shock
Pathophysiological changes in obstetric shock
are predominantly associated with
(a) General changes due to hypovolemia
and
(b) Specific changes due to liberation of
endotoxin.

6. CLASSIFICATION OF SHOCK contd......
2 Septic shock (endotoxic shock):
Associated typically with septic abortion, chorioamnionitis,
pyelonephritis, and endometritis.
Hypotension (systolic BP < 90 mm Hg) is due to sepsis resulting in
derangements in organ functions.
Hypotension persists in spite of adequate fluid resuscitation
3 Cardiogenic shock:
• Myocardial infarction
• Cardiac arrest (asystole or ventricular fibrillation)
• Cardiac tamponade
Characterized by
↓ Systolic Pressure (< 80 Mm Hg),
↓ Cardiac Index (< 1.8 L / Min/M2) And
↑ Left Ventricular Filling Pressure (> 18 Mm Hg)

7. CLASSIFICATION OF SHOCK contd......
4. Extracardiac Shock.
• Massive pulmonary embolism,
• Amniotic fluid embolism,
• Anaphylaxis, Drug-induced, shock Associated with spinal
anesthesia
• Neurogenic.
• Chemical injury: Associated with aspiration of
gastrointestinal contents during general anesthesia
(Mendelson’s syndrome).
• Shock associated with DIC ,IUD.

8. Endotoxic shock
• Endotoxic shock usually follows infection with Gram-
negative organisms (75-80%).
• The most common organism involved is Ecoli (50%).
• Other organisms occasionally responsible for
endotoxic shock are, Pseudomonasaeruginosa,
Klebsiella, Proteus, Bacteroides and Aerobacter
aerogenes.
• Gram-positive organisms (Staphylococcus,
Streptococcus), anaerobes (Bacteroides fragilis),
Clostridium group are less common (20%).

9. Pathophysiology of endotoxic shock
MODS
Persistant
Hypotension
IRREVERSIBLE PHASE
Myocardial Effects : Myocardial contraction,
L V Ejection fraction, L V dilatation, Cardicout put
Platelet Activating Factor, Β
Endorphins , Interferron -ϓ
• Cytokines ( Il 1,6 TNF α )
• Arachidonic Acid Metabolites :PGI2, I ,PGE2. TX A2
• Leukotrienes
Nutrophils , Macrophages, Monocytes , Endothelial Cells ( in blood vessels)
(Aerobic and anaerobic)
SIRS
Endotoxin ( lipo-poly saccharids)
Septic abortion , septic peritonitis , pyelonephritis, chorioamnionitis, endometritis
Gram negative organisms
( 70-80%)
Vascular Effects: Vaso-dilatation, Vaso-constriction, Maldistribution
Blood Flow, Endothelial Cell Injury, ARDS, Hypotension, Tissue
hypoperfusion , Intravascular thrombosis, Capillary permiability
ENDOCRINE MEDIATORS AUTOCRINE AND PARACRINE ACTION
Endothilin 1, Cytotoxic Enzymes,
Compliments C3a, C5a
Infection
Gram positive organisms
( 20-30%)
Extoxin ( lipo-toichoic acid)
METABOLIC
ACIDOSIS
SEVERE MYOCARDIAL
DYSFUNCTION
DIC

10. Pathophysiology of Endotoxic Shock
• Bacterial endotoxin causes selective vasospasm at the
postcapillary end.
• Blood is pooled in the capillary bed.
• There is inhibition of myocardial function and cellular
damage through complex biochemical changes.
• The patient in early septic shock feels warm due to
vasodilatation.This is called warm shock.
• In the late phase, the patient feels cold due to
vasoconstriction (sympathetic squeeze).
• Patient’s skin becomes cold, clammy and ashen gray.
This is called cold shock or late shock

11. The various biochemical and pathological
changes observed in endotoxic shock are:
(i) Diffuse intravascular coagulation.
(ii) Increased capillary permeability.
(iii) Metabolic acidosis.
(iv) Release of superoxide (O2 –) and hydroxyl
(OH–) radicals.
(v) Failure of sodium pump operation.
(vi) Water and electrolyte imbalance.
(vi) Excessive and uncontrolled systemic
inflammatory response (SIR) can lead to organ
changes.

12. Systemic inflammatory response syndrome(SIRS)
It is manifested by two or more of the following
conditions:
(i) Temperature > 38°C or < 36°C
(ii) HR > 90 bpm
(iii) Respiratory rate > 24/min or
(iv) PaCO2 < 32 mm Hg or
(v) WBC > 12000/μl or
leukopenia: < 4000/μl or more than 10%
immature forms.

13. Organ changes in Endotoxic shock
Depend on the degree of hypo-perfusion and
extent of the underlying pathology

14. Organ changes in Endotoxic shock
Endotoxins have got special affinity for kidneys and
lungs for reasons which are not very clear.
(a) Kidney Patchy and massive cortical necrosis leading to oliguria,
anuria and azotemia.
Persistent hypotension leads to acute tubular necrosis and
ultimately renal failure.
(b) Liver Hepatocellular necrosis and degeneration ultimately leading to
hepatic failure
(c) GI tract Hypoxic mucosal injury increases systemic sepsis by
translocation of intraluminal microbes. Congestion,
hemorrhage and ulceration are responsible for hematemesis
(d) Lungs
Congestion or atelectasis leads to tachypnea or dyspnea, progressive
hypoxemia and reduced pulmonary compliance- ARDS results from
increased capillary permeability and thickening of the alveolar capillary
membranes.
Arterial PaO2 will fall low (< 65 mm Hg) which needs Mechanical ventilation

15. Organ changes in Endotoxic shock
(e) Coagulopathy (DIC)
It is due to diffuse endothelial injury, microvascular
thrombosis and thrombocytopenia.
(f ) Adrenal insufficiency
is due to critical illness related corticosteroid insufficiency
(CIRCI). CIRCI causes hypotension which is refractory to
fluid replacement. Vasopressor therapy is needed.
(g) Heart Cardiac output decreases depending on the degree of
hypotension, hypoperfusion and vasoconstriction.

16. Heart changes in Endotoxic shock
(g) Heart Cardiac output decreases depending on the degree of
hypotension, hypoperfusion and vasoconstriction.
Myocardial ischemia
Cardiac dysfunction
Dysrhythmias
Cardiac failure
Left Ventricular end diastolic pressure (LVEDP)
Pulmonary edema
Tissue hypoxia
Ultimately multiple organ failure develops.

17. Table Classification of haemorrhgic shock (based on blood
volume , assuming total blood volme 6L)
Parameter Class I Class II Class III Class IV
Blood volume loss in % < 15 15–30 30–40 > 40
Loss in mL 750 mL 750–1500 1500–2000 > 2000
Heart rate No change Tachycardia Mod tachy Marked tachy
Blood pressure Normal Normal Decreased Decreased
Resp Rate Normal Tachypnea Tachypnea Marked tachypnea
Cardiac output Normal Mildly reduced Reduced Markedly reduced
Mean arterial pressure Normal Mildly decreased < 60 mm Hg Decreased
Systemic vascular Resistance Normal Increased Increased Increased
Urine output (mL/hr) > 30 20–30 5–15 Anuric
Mental status Normal Anxious Confused Obtunded

18. MANAGEMENT OF ENDOTOXIC SHOCK

19. Investigations to organize in a patient with
septic shock
• CBC, Hematocrit, coagulation profile, (platelet count, serum
fibrinogen, FDPs, PT, APTT), liver and renal function tests.
• Chest radiograph
• USG, CT or MRI may be needed for localizing pelvic
pathology
• ECG.. -- monitoring.

20. Principles of management ENDOTOXIC SH OCK
(a) To correct the hemodynamic unstability
due to sepsis (endotoxin)
(B) Appropriate supportive care
(C) To remove the source of sepsis.

21. General principles Endotoxic Shock contd
• Two wide bore cannulas are sited.
• Foley’s catheter is inserted.
• Oxygenation with (face mask) is to be given.
• Mechanical ventilation may be needed in a severe
case.
• Hemodynamic resuscitation

22. Goal of hemodynamic resuscitation
We hould be able to maintain
(a) Mean arterial pressure >70 mm of Hg.
(b) CVP of 10-15 cm H2O.
(c) Urine output 0.5 ml / kg/hour.
(d) Central venous oxygen saturation >70%.

23. Hemodynamic resuscitation
This includes administration of
• Oxygen
• Antibiotics,
• Intravenous fluids,
• Adjustment of acid base balance,
• Steroids
• Inotropes.
• Prevention and treatment of DIC.
• Toxic myocarditis.
• Elimination of the source of infection.

24. Antibiotics:
• Endotoxic shock is most commonly due to Gram-negative organisms, so
proper antibiotics should be administered in adequate doses.
• The choice of antibiotic will depend upon the sensitivity test but before the
report is available, broad spectrum antibiotics covering Gram-positive,
Gram-negative and anaerobic organisms should be started.
• Ampicillin (2G IV every 6 hours),+ Gentamicin (2 mg/kg IV loading dose
followed by 1.5 mg/kg IV every 8 hours) + metronidazole (400 mg IV every
8 hours) is a good combination to start with.
• Alternative regimen is to give
Imipenem – cilastatin (500 mg IV every 6 hours),
Meropenem (1 gm every 8 hours)
Ertapenem (1 gm IV every 24 hours)
. Clindamycin 600 mg IV infusion (single dose) is an alternative to
Metronidazole.

25. Intravenous fluids and electrolytes
• Septic shock associated with hemorrhagic
hypotension should be treated by liberal infusion and
blood transfusion. Isotonic crystalloid (Ringer’s
lactate/normal saline) should be given.
• The amount of fluid to be administered can be
precisely assessed by monitoring the pulse, BP, urine
output and recording the central venous pressure.
• Alternatively, a rough calculation of the amount of fluid
to be administered can be assessed by the volume of
urinary output and its specific gravity.

26. Oliguria with high specific gravity is an indication
for liberal fluid administration, whereas a low
specific gravity indicates fluid restriction.
Impairment of renal function contraindicates
administration of electrolytes. Estimation of
blood electrolytes (Na, K, bicarbonate) is a
helpful guide.

27. Correction of acidosis:
• Acidosis and hypoxemia depress myocardial
contractility.
• Bicarbonate should be administered to correct
persistent Metabolic acidosis (pH < 7.2) only.
• A reasonable first dose would be 50-100 mEq
(60–110 mL of 7.5%) of sodium bicarbonate
solution.
• Further doses will depend on the clinical state of
the patient and blood gas analysis result.

28. Maintenance of blood pressure:
• Inotropic agents—used in a critically ill patient
when there is hypotension (MAP < 60 mm Hg) and
impaired perfusion of vital organs despite
adequate volume replacement, inotropes should
be used.
• Adrenaline, Noradrenaline, Dopamine and
Dobutamine have both INOTROPIC and
VASOCONSTRICTIVE effects.

29. Vasodilator therapy:
• In selected cases, (MAP > 70 mm Hg) after load
reduction may improve stroke volume and
reduce ventricular wall tension.
• Sodium nitroprusside and nitroglycerin could be
used for that purpose.
• This is done under continuous hemodynamic
monitoring.

30. Dopamine
• Dopamine is still the drug of choice.
• Its main action is on β-adrenoreceptors, increasing
cardiac contractility and cardiac output without
change in rate.
• In a dose of 1-3 μg /Kg/1 min as 1 dose.
• It increases renal cortical plasma flow and GFR.
• Inotropic effect is observed with 3-10 μg Kg–1 min–
1 doses.

31. Inotrops contd.......
• Dobutamine (β1 and β2 adrenergic)
is used in cardiogenic shock.
• Adrenaline is a very potent α and β agonist and is
sometimes used in patients who do not respond to
dopamine or dobutamine especially in septic shock.

32. Diuretic therapy
To reduce fluid overload (preload) and
pulmonary edema, diuretics should be
used. Frusemide is the drug of choice.

33. Corticosteroids:
• Patients with severe sepsis develop systemic inflammatory
response syndrome or relative adrenal insufficiency (CIRCI).
• Corticosteroids could be used as anti-inflammatory agents to
improve mortality.
• The dose recommended in septic shock is 50 mg of
hydrocortisone per kg body weight.
• The advantages claimed are:
(i) exerts an anti-inflammatory effect at the cellular level
(ii) stabilizes lysosomal membrane
(iii) counteracts anaerobic oxidative mechanism
(iv) improves the regional blood flow (microcirculation) and
thereby reverse the metabolic acidosis
(v) exerts positive inotropic effect to improve cardiac efficiency
(vi) some vasopressor effect.

34. Treatment of diffuse intravascular coagulation:
• When there is low fibrinogen level, reduced
platelet count and increased fibrin degradation
products, heparin therapy should be considered.
• As a prophylactic measure, Heparin 5000 IU
subcutaneous or intravenous route at 8 hourly
interval can be given safely.
• Alternatively, fresh frozen plasma or whole blood
transfusion could be done.

35. Treatment Of Myocarditis:
• Myocarditis most often is associated with septic
hypotension.
• There is no specific treatment apart from the
treatment of endotoxemia.
• Under exceptional circumstances when there is
evidence of congestive cardiac failure or
features of atrial fibrillation or flutter, digitalis may
be administered.

36. Elimination of source of infection
• Surgical intervention should be done to eliminate
the source of infection.
• Evacuation of the retained products of conception
or hysterectomy for a case with septic abortion or
puerperal sepsis should be done without delay.
Removal of the source of infection may make the
patient hemodynamically stable.
• Hysterectomy has been advocated in
unresponsive endotoxic shock following septic
abortion or puerperal sepsis

37. Intensive insulin therapy
• Is done in patients with severe sepsis and septic
shock to maintain normal blood glucose level.
• These patients often develop hyperglycemia
which further increases the risk of septicemia
and death.

38. H2–blockers
• Antacids to reduce the stress ulcer of gastric
mucosa either by oral or H2-blocking agents
(IV) are used.

39. Nutritional support
• Nutrition is maintained as total parenteral
nutrition (TPN).
• Usually 20-30 Kcal/kg/day is equally distributed
between fat and carbohydrate.
• Serum electrolytes, BUN, glucose, creatinine
should be monitored on a regular basis.

40. Recombinant human-activated protein C
therapy
• Recombinant human-activated protein C therapy
(Drotrecogin Alfa):
• Activated protein C is one endogenous protein that
inhibits inflammation, thrombosis and promotes
fibrinolysis.
• It reduces mortality in patients with severe
sepsis as it reduces coagulopathy and
inflammation.

41. The end

62. Extra slides

63. PATHOGENESIS
OF
HYPO-VOLEMIC
SHOCK