Hemodynamic Stabilisation in Septic shock Dr. T.R.Chandrashekar Intensivist K.R. Hospital Bangalore

Septic shock Macrocirculation Perfusion with adequate oxygen Microcirculation Improper delivery and utilisation Mitochondrial dysfuction Microcirculatory and Mitochondrial Distress syndrome (MMDS) MMDS = sepsis +genes+ therapy + time Adequate perfusion pressure MAP>=65mmHg Adequate oxygen delivery CO x Hb x SPO2 x 1.34 + .003 x PaO2

Macro-Circulation

Volume Vessel tone Heart function If shock is prolonged, mechanisms of shock are combined Physiologic Classification of Acute Circulatory Insufficiency Fluids / blood Vasopressors Inotropes

CO Preload Fluid Responsiveness is a dynamic parameter that reflects the degree by which the CO responds to changes in preload “ Will my patient respond to fluids?”

75% Factors that influence mixed and central venous SO 2 _ + Hypothermia Anesthesia  PaO2  Hb  Cardiac output  PaO2  Hb  Cardiac output Stress Pain Hyperthermia Shivering  VO2  DO2  DO2  VO2

SvO2 closely correlates with ScvO2

Insert CVP/SvcO 2 SvO2 >70% SvO2 <70% Sepsis? Repeat Fluid challenge 250ml/ 5mins Haemodynamic improvement ? Consider global/right ventricular failure Echocardiography that preceeds cardiac output monitoring Yes Continue until normal values obtained No Vasopressors Hypovolaemic/ Haemorrhagic/ cause? No response Continue until normal values obtained Haemodynamic improvement Repeat fluid challenge (250ml/5mins) or transfusion if necessary. Echocardiography that preceeds CO monitoring CVP N or low CVP high CVP low

Micro- Circulation

“… Our understanding of hemodynamic mechanisms (in distributive shock) depends not so much on the total volume of blood that flows past the aortic valve or the cardiac output as on the amount of blood delivered to the exchange sites. Even though cardiac output may be substantial, if that blood flow does not arrive at the exchange sites, the ultimate metabolic detriment is no different from low cardiac output without shunt flow.” Weil MH, Shubin H (1971) Adv Exp Med Biol 23:13-23.

Shunting model of sepsis O 2 lactate CO 2 v a Implication : that active recruitment of the microcirculation is an important component of resuscitation. Ince C & Sinaasappel M (1999) Crit Care Med 27:1369-1377

Spronk P, Zandstra D, Ince C (2004) Critical Care 8:462-468 Sepsis is a disease of the microcirculation

Mitochondrial Dysfunction in Cell Injury Increased cytosolic Ca 2+ , oxidative stress, lipid peroxidation Mitochondrial PermeabilityTransition Cytochrome c and other pro-apoptotic proteins Apoptosis Robbins & Cotran Pathologic Basis of Disease: 2005

Functional and Morphologic Consequences of Decreased ATP During Cell Injury Ischemia Oxidative Phosphorylation ATP Na pump Influx of Ca 2+ H 2 0, and Na + Efflux of K + ER swelling Cell swelling Blebs Clumping chromatin Anaerobic glycolysis Glycogen pH Lipid deposition Detachment of ribosomes Protein synthesis

Pump failure or mitochondrial dysfunction Hemodynamic failure Pump failure Mitochondrial dysfunction Hemodynamic and mitochondrial failure Energy failure BE - Lactate Volume test VO 2  Lactate  VO 2  Lactate  Dobutamine test VO 2  Lactate  VO 2  Lactate 

Orthogonal polarization spectral (OPS) imaging

Capillary flow in sepsis

Microcirculation Recruitment Manoeuvres Ince C (2005) Critical Care 9:S13-S19 Correct pathological flow heterogeneity, microcirculatory shunting and restore autoregulatory dysfunction by control of inflammation, vascular function and coagulation. Avontuur (1997) Cardiovas Res 35:368-376. Siegmund M (2005) Inten Care Med 31:985-992 . Open the microcirculation and keep it open by support of the pump, fluids, vasodilators and restricted use of vasopressor agents. : Boerma (2005) Acta Anaesthesiol Scand. 49(9):1387-90. Spronk (2001) The Lancet 360:1395-1396 Siegemund (2006) Intensive Care Med

Sublingual OPS imaging in a patient with septic shock after pressure guided volume resuscitation. the same patient after subsequent nitroglycerin 0.5 mg ivbolus Nitroglycerin promotes microvascular recruitment in septic and cardiogenic shock patients Spronk, Ince, Gardien, Mathura, Oudemans-van Straaten, Zandstra DF. (2002) The Lancet 360:1395-1396.

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