Sections View Full Chapter Figures Tables Videos Full Chapter Figures Tables Videos Supplementary Content + DEFINITIONS Download Section PDF Listen +++ ++ Possibly harmful systemic response: Two or more of the following: – Fever (oral temperature >38°C [100.4°F]) or hypothermia (oral temperature <36°C [96.8°F]) – Tachypnea (>24 breaths/min) – Tachycardia (>90 beats/min) – Leukocytosis (>12,000/μL), leukopenia (<4000/μL), or >10% bands; may have a noninfectious etiology Sepsis (or severe sepsis): Harmful systemic response (including some degree of organ hypofunction) with a proven or suspected microbial etiology Septic shock: Sepsis with hypotension (arterial bp <90 mmHg or 40 mmHg below pt’s normal bp for at least 1 h despite fluid resuscitation) or need for vasopressors to maintain systolic bp ≥90 mmHg or mean arterial bp ≥70 mmHg + ETIOLOGY Download Section PDF Listen +++ ++ Blood cultures are positive in 20–40% of sepsis cases and in 40–70% of septic shock cases. For infected pts in ICUs, respiratory infections have been most common (64%). Microbiologic results have revealed that 62% of isolates are gram-negative bacteria (most commonly Pseudomonas spp. and Escherichia coli), 47% are gram-positive bacteria (most commonly Staphylococcus aureus), and 19% are fungi (most commonly Candida spp.), with some cultures being polymicrobial. + EPIDEMIOLOGY Download Section PDF Listen +++ ++ The incidence of severe sepsis and septic shock in the United States continues to increase, with >750,000 cases each year contributing to >200,000 deaths. Invasive bacterial infections are a prominent cause of death around the world, especially among young children. Sepsis-related incidence and mortality rates increase with age and preexisting comorbidity, with two-thirds of cases occurring in pts with significant underlying disease. The increasing incidence of sepsis has been attributable to the aging of the population, longer survival of pts with chronic diseases, a relatively high frequency of sepsis among AIDS pts, and medical treatments that circumvent host defenses (e.g., immunosuppressive agents, indwelling catheters, and mechanical devices). + PATHOPHYSIOLOGY Download Section PDF Listen +++ +++ Local and Systemic Host Responses ++ Hosts have numerous receptors that recognize highly conserved microbial molecules (e.g., lipopolysaccharide, lipoproteins, double-stranded RNA), triggering the release of cytokines and other host molecules that increase blood flow and neutrophil migration to the infected site, enhance local vascular permeability, and elicit pain. Many local and systemic control mechanisms diminish cellular responses to microbial molecules, including intravascular thrombosis (which prevents spread of infection and inflammation) and an increase in anti-inflammatory cytokines (e.g., IL-4 and IL-10). +++ Organ Dysfunction and Shock ++ Widespread vascular endothelial injury is believed to be the major mechanism for multiorgan dysfunction. Septic shock is characterized by compromised oxygen delivery to tissues followed by a vasodilatory phase (a decrease in peripheral vascular resistance despite increased levels of vasopressor catecholamines). + CLINICAL FEATURES Download Section PDF Listen +++ ++ Hyperventilation that produces respiratory alkalosis Encephalopathy (disorientation, confusion) Acrocyanosis and ischemic necrosis of peripheral tissues (e.g., digits) due to hypotension and DIC Skin: hemorrhagic lesions, bullae, cellulitis, pustules. Skin lesions may suggest specific pathogens; e.g., petechiae and purpura suggest Neisseria meningitidis, and ecthyma gangrenosum suggests Pseudomonas aeruginosa. GI: nausea, vomiting, diarrhea, ileus, cholestatic jaundice +++ Major Complications ++ Cardiopulmonary manifestations – Ventilation-perfusion mismatch, increased alveolar capillary permeability, increased pulmonary water content, and decreased pulmonary compliance impede oxygen exchange and lead to ARDS (progressive diffuse pulmonary infiltrates and arterial hypoxemia) in ~50% of pts. – Hypotension: Normal or increased cardiac output and decreased systemic vascular resistance distinguish septic shock from cardiogenic and hypovolemic shock. – The ejection fraction is decreased, but ventricular dilation allows maintenance of a normal stroke volume. Adrenal insufficiency: may be difficult to diagnose in critically ill pts Renal manifestations: oliguria or polyuria, azotemia, proteinuria, and renal failure due to acute tubular necrosis Neurologic manifestations: delirium in the acute phase, polyneuropathy with distal motor weakness in prolonged sepsis. Survivors may have long-term cognitive impairment. Immunosuppression: Pts may have reactivation of HSV, CMV, or VZV. +++ Laboratory Findings ++ CBC: leukocytosis with a left shift, thrombocytopenia Coagulation: prolonged thrombin time, decreased fibrinogen, presence of d-dimers suggestive of DIC. With DIC, platelet counts usually fall below 50,000/μL. Chemistries: metabolic acidosis, elevated anion gap, elevated lactate levels LFTs: transaminitis, hyperbilirubinemia, azotemia, hypoalbuminemia + DIAGNOSIS Download Section PDF Listen +++ ++ Definitive diagnosis requires isolation of the microorganism from blood or a local site of infection. Culture of infected cutaneous lesions may help establish the diagnosis. ++ TREATMENT: SEPSIS AND SEPTIC SHOCK Pts in whom sepsis is suspected must be managed expeditiously, if possible within 1 h of presentation. Antibiotic treatment: See Table 12-1. Removal or drainage of a focal source of infection Remove indwelling intravascular catheters; replace Foley and other drainage catheters; drain local sources of infection. Rule out sinusitis in pts with nasal intubation. Image the chest, abdomen, and/or pelvis to evaluate for abscess. Hemodynamic, respiratory, and metabolic support Initiate treatment with 1–2 L of normal saline administered over 1–2 h, keeping the CVP at 8–12 cmH2O, urine output at >0.5 mL/kg per hour, and mean arterial bp at >65 mmHg. Add vasopressor therapy if needed. If hypotension does not respond to fluid replacement therapy, hydrocortisone (50 mg IV q6h) should be given. If clinical improvement results within 24–48 h, most experts would continue hydrocortisone treatment for 5–7 days. Maintain oxygenation with ventilator support as indicated. Recent studies favor the use of low tidal volumes—typically 6 mL/kg of ideal body weight—provided the plateau pressure is ≤30 cmH2O. Erythrocyte transfusion is recommended when the blood Hb level decreases to ≤7 g/dL, with a target level of 9 g/dL. General support: Nutritional supplementation should be given to pts with prolonged sepsis (i.e., that lasting >2–3 days), with available evidence suggesting an enteral delivery route. Prophylactic heparin should be administered to prevent deep-venous thrombosis if no active bleeding or coagulopathy is present. Insulin should be used only if it is needed to maintain the blood glucose concentration below ~180 mg/dL. ++Table Graphic Jump LocationTABLE 12-1INITIAL ANTIMICROBIAL THERAPY FOR SEVERE SEPSIS WITH NO OBVIOUS SOURCE IN ADULTS WITH NORMAL RENAL FUNCTIONView Table||Download (.pdf) TABLE 12-1INITIAL ANTIMICROBIAL THERAPY FOR SEVERE SEPSIS WITH NO OBVIOUS SOURCE IN ADULTS WITH NORMAL RENAL FUNCTION Clinical Condition Antimicrobial Regimens (Intravenous Therapy) Immunocompetent adult The many acceptable regimens include (1) piperacillin-tazobactam (3.375 g q4–6h); (2) imipenem-cilastatin (0.5 g q6h), ertapenem (1 g q24h), or meropenem (1 g q8h); or (3) cefepime (2 g q12h). If the pt is allergic to β-lactam agents, use ciprofloxacin (400 mg q12h) or levofloxacin (500–750 mg q12h) plus clindamycin (600 mg q8h). Vancomycin (15 mg/kg q12h) should be added to each of the above regimens. Neutropenia (<500 neutrophils/μL) Regimens include (1) imipenem-cilastatin (0.5 g q6h) or meropenem (1 g q8h) or cefepime (2 g q8h) or (2) piperacillin-tazobactam (3.375 g q4h) plus tobramycin (5–7 mg/kg q24h). Vancomycin (15 mg/kg q12h) should be added if the pt has an indwelling vascular catheter, has received quinolone prophylaxis, or has received intensive chemotherapy that produces mucosal damage; if staphylococci are suspected; if the institution has a high incidence of MRSA infections; or if there is a high prevalence of MRSA isolates in the community. Empirical antifungal therapy with an echinocandin (for caspofungin: a 70-mg loading dose, then 50 mg daily), voriconazole (6 mg/kg q12h for 2 doses, then 3 mg/kg q12h), or a lipid formulation of amphotericin B should be added if the pt is hypotensive, has been receiving broad-spectrum antibacterial drugs, or remains febrile 5 days after initiation of empirical antibacterial therapy. Splenectomy Cefotaxime (2 g q6–8h) or ceftriaxone (2 g q12h) should be used. If the local prevalence of cephalosporin-resistant pneumococci is high, add vancomycin. If the pt is allergic to β-lactam drugs, vancomycin (15 mg/kg q12h) plus either moxifloxacin (400 mg q24h) or levofloxacin (750 mg q24h) should be used. IV drug user Vancomycin (15 mg/kg q12h) is essential. AIDS Cefepime alone (2 g q8h) or piperacillin-tazobactam (3.375 g q4h) plus tobramycin (5–7 mg/kg q24h) should be used. If the pt is allergic to β-lactam drugs, ciprofloxacin (400 mg q12h) or levofloxacin (750 mg q12h) plus vancomycin (15 mg/kg q12h) plus tobramycin should be used. Abbreviation: MRSA, methicillin-resistant Staphylococcus aureus.Source: Adapted in part from DN Gilbert et al: The Sanford Guide to Antimicrobial Therapy, 43rd ed, 2013, Antimicrobial Therapy, Inc., Sperryville, VA. + PROGNOSIS Download Section PDF Listen +++ ++ In all, 20–35% of pts with severe sepsis and 40–60% of pts with septic shock die within 30 days, and further deaths occur within 6 months. Prognostic stratification systems (e.g., APACHE II) can estimate the risk of dying of severe sepsis. + PREVENTION Download Section PDF Listen +++ ++ Nosocomial infections cause most episodes of severe sepsis and septic shock in the United States. Measures to reduce those infections could reduce the incidence of sepsis. ++ For a more detailed discussion, see Munford RS: Severe Sepsis and Septic Shock, Chap. 325, p. 1751, in HPIM-19.