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Physiological changes, clinical features, and general management of infected patients 

Physiological changes, clinical features, and general management of infected patients

Physiological changes, clinical features, and general management of infected patients

Todd W. Rice

and Gordon R. Bernard


July 30, 2015: This chapter has been re-evaluated and remains up-to-date. No changes have been necessary.


New proinflammatory cytokines IL-17 and macrophage migration inhibitory factor.

Immunosuppression in late sepsis.

Procoagulant-anticoagulant and inflammatory interactions.

Vasopressin—role in septic shock.

Role of corticosteroid insufficiency and low-dose corticosteroid therapy.

Withdrawal of drotrecogin alfa (activated) or recombinant human activated protein C.

Failure of eritoran tetrasodium, anti-Toll-like receptor (TLR)-4.

Updated on 31 May 2012. The previous version of this content can be found here.
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date: 25 April 2017

Pathophysiological mechanisms

The host response to an infectious stimulus involves an intricate link between the inflammatory and coagulation systems, also mechanisms designed to limit damage to normal tissues. Key elements are: (1) the inflammatory cascade—antigens from infectious agents stimulate macrophages and monocytes (and other cells) via Toll-like receptors to release tumour necrosis factor α‎ (TNFα‎), resulting in a cascade of pro-inflammatory cytokine release which is a vital component of the host’s attempt to control and eradicate infection, but unfortunately can also result in damage to both infected and uninfected host tissues; inflammatory mediators with prolonged actions or appearing later in the course of sepsis are likely to play an important role in determining prognosis; (2) the anti-inflammatory cascade—a compensatory response involving anti-inflammatory cytokines, soluble receptors, and receptor antagonists directed against pro-inflammatory cytokines that is intended to localize and control the systemic proinflammatory response to the infection; (3) the coagulation cascade—activated in an attempt to contain infection locally and prevent spread to other parts of the body; platelets are activated, procoagulant pathways are initiated, and anticoagulant mediators are down-regulated; (4) the anticoagulation cascade—the coagulation response to sepsis is regulated via antithrombin, tissue factor pathway inhibitor (TFPI), activated protein C (APC), and fibrinolysis.

Clinical features

Definitions—(1) Systemic inflammatory response syndrome (SIRS)—which can occur as a result of an infectious or noninfectious insult—requires the presence of at least two of the following: (a) hyper- or hypothermia, (b) tachycardia, (c) tachypnoea or hyperventilation, (d) leucocytosis, leucopenia or left shift. (2) Sepsis—a suspected or confirmed infection plus criteria for SIRS. (3) Severe sepsis—sepsis resulting in the acute dysfunction of at least one organ system. (4) Septic shock—infection resulting in hypotension despite adequate fluid resuscitation.

Management—key elements are (1) antibiotics—often initiated empirically before culture results are available; (2) control of the source of infection—searching for the site of infection so that it can be eradicated should begin as soon as haemodynamic and respiratory status are stabilized; antibiotics without source control often fail; (3) early goal-directed resuscitation—requiring (a) crystalloid infusions to maintain central venous pressure, (b) vasopressors if arterial pressure remains low, and (c) transfusion of packed red blood cells and/or infusion of dobutamine if central venous oxygen saturation remains low; (4) consideration of other treatments—many specialists advocate recombinant APC for patients with severe sepsis who have a low risk of bleeding and a high risk of death.

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