Shock

1. Shock • Term “choc” – French for “push” or impact was first published in 1743 by the physician LeDran • Belief – symptoms arose from fear or some other form of altered cerebral function • Crile in 1899 showed that replacement of blood volume decreased mortality experimentally

2. Determinants of Shock • Inadequate tissue perfusion • Sustained loss of effective circulatory blood volume • Breakdown of cellular metabolism and microcirculatory homeostasis • Hypoperfusion of peripheral tissue that leads to a diminutive transcapillary exchange function • Disproportion between VO2 and DO2

3. Hemodynamic States of Shock • Hyperdynamic • Hypodynamic • Related to: • Cardiac Output (CO) • Systemic Vascular Resistance (SVR)

4. Pathophysiology of Shock • Shock develops with inadequate capillary perfusion by decreased Cardiac Output following heart attack (cardiogenic shock) or blood/volume loss (hypovolemic shock)

5. Clinically • Hypotension. • Poor Tissue Perfusion with Anaerobic Metabolism and lactate production. • Poor Renal Perfusion will cause a Decrease in Urine Output. • Poor Cerebral Perfusion will cause an and Altered Mental status. • Other clinical parameters depend on Etiology. E.g. Warm Extremities in Septic Shock vs Cold Clammy Extremites in Cardiogenic shock.

6. Mediators of Shock • Toxins • Endotoxins • Oligo- and polypeptides • Complement Factors • Opiods • TNF, Interleukins • Fatty Acid Derivatives • Arachidonic acid metabolites • Other

7. Main Classes of Shock • Hypovolemic Shock • Distributive Shock • Cardiogenic Shock • Obstructive Shock

8. Hypovolemic Shock • Hemorrhagic/Traumatic • Dehydrative • Burn

9. Obstructive Shock • Pulmonary Embolism • Cardiac Tamponade • Pneumothorax

10. Distributive Shock • Septic • Anaphylactic/ Anaphylactoid • Neurogenic

11. Systemic inflammatory response syndome (SIRS) • Evidence of is indicated by at least two of the following: 1. Fever or hypothermia—Core body temperature of greater than or equal to 38ºC or less than or equal to 36ºC 2. Tachypnea—greater than or equal to 20 breaths per minute or need for mechanical ventilation for an acute process 3.. Tachycardia—heart rate greater than or equal to 90 beats per minute, unless the patient has a preexisting tachycardia 4. White blood cell count—greater than or equal to 12,000 cells/mm3 or less than or equal to 4,000 cells/mm3, or greater than 10% bands on differential

12. Sepsis Continued • Sepsis is SIRS due to a presumed or known site of infection. • Severe sepsis is sepsis with an acute associated organ failure. • Septic shock, a subset of severe sepsis, is defined as a persistently low mean arterial blood pressure despite adequate fluid resuscitation. • Refractory septic shock is a persistently low mean arterial blood pressure despite vasopressor therapy and adequate fluid resuscitation

13. A sepsis-induced organ failure is indicated by one of the following criteria: • Cardiovascular dysfunction—mean arterial pressure less than or equal to 60 mm Hg, the need for vasopressors to maintain this blood pressure in the face of adequate intravascular volume (central venous pressure greater than 8 or pulmonary artery occlusion pressure greater than 12), or after an adequate fluid challenge has been given • Respiratory organ failure—an arterial oxygen pressure/fraction of inspired oxygen ratio less than 250 in the absence of pneumonia or less than 200 in the presence of pneumonia • Renal dysfunction—urine output less than 0.5 mL/kg/hr for 1 hour in the face of adequate intravascular volume or after an adequate fluid challenge • Hematologic dysfunction—thrombocytopenia with 80,000 platelets/mm3, a 50% drop in the previous 3 days, or a prothrombin-INR greater than 1.2 that cannot be explained by liver disease or concomitant warfarin usage • Unexplained metabolic acidosis—a pH less than 7.30 and a plasma lactate greater than 1.5 times the upper limit of normal for the laboratory

15. Addition of Thermodilution Cardiac Output Ganz & Swan: Am J Cardiol 1972;29,241.

17. Pulmonary Artery Catheter Waveforms Right Atrium Right Ventricle Pulmonary Artery PCWP

18. PA Cath Measured Parameters • Central Venous Pressure • Pulm Artery Occlusion Pressure (Wedge Pressure) • Pulmonary Artery Pressures • Cardiac Output (CCO) nl = 4 - 8.0 L/min • Mixed Venous Saturation

19. Calculated Parameters • Systemic Venous Resistance (SVR) • Pulmonary Vascular Resistance (PVR) • Stroke Volume (SV) nl = 60 - 100 ml SV = CO/HR x 1000 • Arterial Venous O2 Content Difference

20. Calculating Ventricular Volume SVI REF CI HR x REF RVEDVI - right ventricular end-diastolic volume index nl = 60 - 100 ml/m2 SVI - stroke volume index REF - right ventricular ejection fraction RVEDVI = =

21. Type Preload CO PVR SVR Hemmorrhagic Anaphylactic Cardiogenic Septic (Hyperdynamic) Septic (Hypodynamic) Hemodynamic Characteristics in Different Types of Shock /

23. Example The wavefrom shown in this figure was observed while attempting to advance a pulmonary arterial catheter, with the Balloon inflated, from the proximal pulmonatry artery to a “wedged” position. Which one of the following best explains the terminal portion of the depicted waveform? a. Pulmonary hypertension b. Mitral regurgitation c. Severe left ventricular dysfunction d. Obstruction of the catheter tip e. Pericardial tamponade

24. An Alternative to the Pulmonary Artery Catheter Type Natriuretic Peptide Maesel et al: N Engl J Med 2002;347,161-167

25. B Type Natriuretic Peptide • Useful for distinguishing Congestive Heart Failure from non cardiac cause of dyspnea. • Values of > than 100pcg/ml is 83.4% Sensitive for diagnosing CHF. • Values of < than 50pcg/ml is 96% Specific in excluding dyspnea as being secondary to CHF. • Correlates with CHF more accurately than history and physical exam. Maesel et al: N Engl J Med 2002;347,161-167

26. Management of Shock • Shock begins when DO2 to the cells is inadequate to meet metabolic demand • The major therapeutic goals in shock therefore are sufficient tissue perfusion and oxygenation • Early diagnosis remains a major problem

28. Inotropic Agents • Vasoactive drugs are an important pharmacologic defense in the treatment of shock. • May be required to support BP in the early stages of shock. • These agents may be needed to: • Enhance CO through the use of inotropic agents. • Maintain vital organ tissue perfusion.

29. Epinephrine  0.02 – 0.5 Norepinephrine  0 - 0.05 – 0.5 Dopamine  DR 2 -12 Dobutamine  2 - 12 Dopexamine DR 0 - 0.9 - 5 Vasopressin Angiotensin III 5 - 20 Amrinone PDI 5 -10 Effects of Inotropic Agents and Vasodilators 1 Drug Receptor CO SVR Dose Range 0 - (g/kg/min)

30. Nifedipine 0 - 0.5 - 10 Nitroglycerin 0 - 3 - 5 Nitroprusside 0 - 0.5 - 5 Prostacyclin 10 - 40 Effects of Inotropic Agents and Vasodilators Drug CO SVR Dose Range (g/kg/min)

31. Dopamine An endogenous precursor of norepinephrine withmultiple dose-related effects • Low Dose (0.5 - 3 mcg/kg/min) • 2 and dopaminergic (DR) effects • Enhanced blood flow to renal and splanchnic beds • Moderate Dose (5 -10 mcg/kg/min) • Positive inotropic effects • High Dose (10-20 mcg/kg/min) • -actions (vasoconstriction)

32. Xigris for Sepsis • Recombinant human activated protein C ([rhAPC] drotrecogin alfa • RhAPC is a molecule that targets the cascade of inflammation and coagulopathy characteristic of sepsis through its antithrombotic, profibrinolytic, and anti-inflammatory properties.

37. New Therapies for Septic Shock • Xigris use limited by cost. • $7 000 dollars for the usual 4 day treatment. • 6% improvement in Mortality: • This means we need to spend $666 666.00 (2/3 of a million dollars) to save a single life. • Is it worth it? Ask Dr. Nalamati.

38. Monitoring of Resusitation in Sepsis. • Inclusion criteria included. • 2 of 4 SIRS Criteria • SBP <90 after 25ml/kg IVF and/or a lactate of >4mmol/l • Then Randomized to Standard therapy vs Interventional Group.

39. Standard Care CVP, Pulse Oximetry, Urine Cath, Art. Line. • CVP >= 8-12mm Hg • MAP >65mm Hg • Urine Output > 0.5ml/kg/hr

40. Treatment group • Standard Care (25ml/kg/IVF) • If Central Venous Oxygen saturation was less than 70% 1. Transfused Blood until Hct>30% 2. If HTN Vasodilators until MAP <65m Hg 3. Dobutamine if above failed to raise Mixed Venous Oxygen Saturation. 4. If above still failed Mech Ventilation and Sedatives

41. Results • All Patient Standard Therapy Mortality was 46.5% • All Patient Treatment Group was 38 % • Septic Shock Standard Therapy Mortality was 56.8% • Septic Shock Treatment Group was 38%.

42. Treatment Differences in First 6hrs Pressor use did not substantially differ.

43. Comments • Impressive study in ER Setting: • Majority of difference was Correction of any Anemia and Early Administration of More IV Fluids and Blood. • Dobutamine may indicated in Cardiogenic Shock. Patients received Dobutamine in this trial did so only after Volume resusitation (see above) and Central Venous Oxygen Saturation remained low indicating they had some underlying Cardiac Dysfunction.