Chap 254 -- Severe Sepsis & Septic Shock

CHAPTER 254: SEVERE SEPSIS AND SEPTIC SHOCK •

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Cardinal signs of the systemic inflammatory response syndrome (SIRS): fever, hypothermia, leucopenia, leukocystosis, tachypnea and tachycardia. SIRS can either be infectious or not. If proven infectious it is called sepsis. When sepsis is associated with dysfunction of organs distant from the site of infection, it is called severe sepsis. Severe sepsis may be accompanied by hypotension or evidence of hypoperfusion. When hypotension cannot be corrected with fluid infusion, is septic shock. Sepsis is usually reversible. Bacteremia- bacteria in blood Septicemia- microbes or their toxins in the blood Fever >38C Hypothermia <36C Tachypnea >24 Tachycardia >90 Leukocystosis >12,000 Leukopenia <4,000 Severe sepsis:

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arterial systolic BP < 90 mmHg or MAP < 70 mmHg urine: 0.5/ml/kh/hr Pao2/FIo2: < 250 or if the lung is dysfunctional <200 Platelet: <80,000/uL or 50% decrease in 3 days pH < 7.30 or a base deficit > 5.0 meq/L and plasma lactate level >1.5x upper limit of normal for reporting lab pulmonary artery wedge pressure > 12 mmHg or CVP > 8 mmHg

Septic shock: sepsis with hypotension, arterial BP of <90 mmHg systolic, or 40 mmHg less than patient’s normal BP for at least 1 hr despite fluid resuscitation or need for vasopressors to maintain systolic blood pressure > 90 mmHg or mean arterial pressure > 70 mmHg Refractory septic shock- Septic shock that lasts for >1 hr and does not respond to fluid or pressor administration Multiple organ dysfunction syndrome (MODS) – dysfunction of more than

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one organ requiring intervention to maintain homeostasis. TNF-a increases in most patients with severe sepsis or septic shock There is a striking propensity to intravascular fibrin deposition, bleeding and thrombosis. Glucocorticoids, cortisol, epinephrine, IL10 and C-reactive proteins reduce the ability of neutrophils to attach to vascular endothelium Widespread vascular endothelial injury is the major mechanism for multiorgan dysfunction. Hallmark of septic shock is decrease in peripheral vascular resistance that occurs despite increased levels of vasopressor catecholamines. Patients with septic shock often show diminished vasoconstrictor responses to catecholamines. This loss of sensitivity has been attributed to down regulation of adrenergic receptors and the elevation of nitric oxide. Fulminant meningococcemia has correlated well with blood endotoxin levels and occurrence of DIC. Uncontrolled local infection may drive to septic reaction. The pathogenesis of severe sepsis may differ according to the infecting microbe, the site of primary infection, the presence and absence of immune defects, and the prior physiologic state of the host. Absence of fever is most common in neonates, elderly patients and in persons with uremia or alcoholism. Hypotension and DIC predispose to acrocyanosis of the digits. When sepsis is accompanied by petechiae or purpura suspect of N. meningitides. A cutaneous lesion almost exclusively for neutropenic patients is ecthyma gangrenosum caused by P. aeruginosa. Raw oyster – Vibrio Vulnificus Generalized erythroderma in a septic patient suggests the toxic shock syndrome due to S. aureus or S. pyogenes. Increased glycolysis Metabolic acidosis Protein catabolism is markedly high.

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Major complications: Cardiopulmonary: ventilation-perfusion matching produces a fall in the arterial po2. Progressive diffuse pulmonary infiltrates and arterial hypoxemia (pao2/fio2 <200) indicate the development of ARDS. ARDS develops in 50% of patients with severe sepsis or septic shock. An elevated capillary wedge pressure (>18 mmHg) suggests fluid volume overload or cardiac failure rather than ARDS. Sepsis induced hypotension usually results from a generalized maldistribution of blood flow and blood volume and from hypovolemia that is due to diffuse capillary leakage of intravascular fluid. Normal or increased cardiac output and decreased systemic vascular resistance differentiates septic shock from the other types of shock. A refractory hypotension is usually due to a low systemic vascular resistance and death results from the refractory shock or the MODS rather than cardiac per se. Renal: oliguria, azotemia, proteinuria Drug-induced renal damage: aminoglycosides Coagulation: endothelial injury or microvascular thrombosis Neurologic: rule out Guillain barre syndrome, metabolic disturbances and toxin activity Laboratory findings: in early sepsis – leukocystosis with a left shift, thrombocytopenia, hyperbilirubinemia and proteinuria, leucopenia may develop. Neutrophils with Dohle bodies or cytoplasmic vacuoles. Severe septic response: thrombocytopenia worsens, presence of D-dimers suggesting DIC Azotemia and hyperbilirubinemia, aminotransferases rise. Active hemolysis suggests clostridial bacteria, malaria, drug reaction or DIC. In the case of DIC, microangiopathic changes may be seen on a blood smear. Hyperventilation --> respiratory alkalosis.

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With respiratory fatigue - metabolic acidosis ABG reveals hypoxemia Diabetic ketoacidosis may exacerbate hypotension Hypoalbuminemia Serum lipid concentrations are high Diagnosis: fever, hypothermia, tachypnea, tachycardia, leukocystosis, leucopenia, acutely altered mental status, thrombocytopenia or hypotension. At least 2 samples of 10 ml each from different sites are obtained for culture. Blood levels of IL6 may also correlate with prognosis Treatment:: antimicrobial therapy should start empirically Catheters should be replaced. Primary goal is to restore adequate oxygen and substrate delivery to the tissues. Adequate organ perfusion is essential. Administration of fluid 1-2 L of normal saline in 1-2 hrs. To prevent pulmonary edema, pulmonary wedge pressure should be maintained at 12-16 mmHg MAP, and 8-12 mmHg CVP. Furosemide can be used. Reasonable goal is to maintain arterial BP of >65 mmHg and systolic BP of >90 mmHg and cardiac index of > 4 L/min /m2. Adrenal insufficiency should be considered in septic patients with refractory hypotension, fulminant meningitides bacteremia, glucocorticoids use, disseminated TB or AIDS. Ventilator therapy is indicated for patients with hypoxemia, hypercapnia, neurologic deterioration or respiratory muscle failure. Erythrocyte infusion is indicated if oxygen delivery is compromised by low hemoglobin concentration. ( <7 g/dL) Bicarbonate for pH 7.20 Fresh frozen plasma for DIC Nutrients: enteral delivery Other measures: drugs that neutralize endotoxin, anti inflammatory drugs that interfere with the mediators of inflammation, anticoagulant drugs.

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Recombinant activated protein for the treatment of severe sepsis and septic shock. Intracranial hemorrhage is the most serious complication. Prognostic stratification: Apache II Prevention: treat nosocomial infections as this is the cause of sepsis.