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
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
“… 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
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.
Perfusion becomes dependent on pressure below a certain mean arterial pressure because autoregulation in various vascular beds can be lost. Supplement goal such as blood pressure with the assessment of global perfusion such as blood lactate concentrations Dopamine increases mean arterial pressure and cardiac output due to an increase in stroke volume and heart rate Norepinephrine increases mean arterial pressure due to vasoconstrictive effects Norepinephrine causes little change in heart rate and less increase in stroke volume compared to dopamine Dopamine causes more tachycardia and may be more arrhythmogenic
Arterial catheter placement in an emergency department is typically not possible or practical. Vasopressin is a direct vasoconstrictor without inotropic or chronotropic effects and may result in decreased cardiac output and hepatosplanchnic flow. Most published reports exclude patients from treatment with vasopressin if the cardiac index is < 2 or 2.5. Low doses of vasopressin may be effective in raising blood pressure in patients refractory to other vasopressors, although no outcome data are available.
Dobutamine is the first-choice inotrope for patients with measured or suspected low cardiac output in the presence of adequate left ventricular filling pressure (or clinical assessment of adequate fluid resuscitation) and adequate mean arterial pressure. The goal of resuscitation should be to achieve adequate levels of oxygen delivery or avoid flow dependent tissue hypoxia. “Two large prospective clinical trials that included critically ill ICU patients who had severe sepsis failed to demonstrate benefit from increasing oxygen delivery to supranormal levels by use of dobutamine.” P. 863