Endotoxic Shock in Obstetrics PPT

This topic is very useful for students and practicing obstetricians

1. Endotoxic shock i n 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: 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 General changes due to hypovolemia and (b) Specific changes due to liberation of endotoxin .

6. CLASSIFICATION OF SHOCK contd...... 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 F illing 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 E coli (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. 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 μ g /Kg/1 min as 1 dose. It increases renal cortical plasma flow and GFR. Inotropic effect is observed with 3-10 μ g 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.

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43. PATHOGENESIS OF HYPO-VOLEMIC SHOCK