Sepsis Flashcards
Bacteremia
Presence of bacteria in blood, as evidenced by positive blood cultures
Systemic inflammatory response syndrome (SIRS)
SIRS may have an infectious or a noninfectious etiology
Two or more of the following conditions: (1) fever (oral temperature >38°C) or hypothermia (<36°C); (2) tachypnea (>24 breaths/min); (3) tachycardia (heart rate >90 beats/min); (4) leukocytosis (>12,000/μL), leukopenia (<4,000/μL), or >10% bands; may have a noninfectious etiology
Sepsis
SIRS that has a proven or suspected microbial etiology
Severe sepsis [1]
When sepsis is associated with dysfunction of organs distant from the site of infection, the patient has severe sepsis.
Severe sepsis (similar to “sepsis syndrome”) [2]
- Cardiovascular: Arterial systolic blood pressure ≤90 mmHg or mean arterial pressure ≤70 mmHg that responds to administration of intravenous fluid
- Renal: Urine output <0.5 mL/kg per hour for 1 h despite adequate fluid resuscitation
- Respiratory: PaO2/FIO2 ≤250 or, if the lung is the only dysfunctional organ, ≤200
- Hematologic: Platelet count <80,000/μL or 50% decrease in platelet count from highest value recorded over previous 3 days
- Unexplained metabolic acidosis: A pH ≤7.30 or a base deficit ≥5.0 mEq/L and a plasma lactate level >1.5 times upper limit of normal for reporting lab
- Adequate fluid resuscitation: Pulmonary artery wedge pressure ≥12 mmHg or central venous pressure ≥8 mmHg
Septic shock [2]
Sepsis with hypotension (arterial blood pressure <90 mmHg systolic, or 40 mmHg less than patient’s normal blood pressure) for at least 1 h despite adequate fluid resuscitation;
or
Need for vasopressors to maintain systolic blood pressure ≥90 mmHg or mean arterial pressure ≥70 mmHg
Septic shock [1]
When hypotension cannot be corrected by
infusing fluids, the diagnosis is septic shock
Refractory septic shock
Septic shock that lasts for >1 h and does not respond to fluid or pressor administration
Multiple-organ dysfunction syndrome (MODS)
Dysfunction of more than one organ, requiring intervention to maintain homeostasis
Host mechanisms for sensing microbes [1]
- A host protein (LPS) binds lipid A and transfers the LPS to CD14 on the surfaces of monocytes, macrophages, & neutrophils.
- LPS then is passed to MD-2, that is bound to toll-like receptor (TLR) 4 to form a molecular complex that transduces the LPS recognition signal to the interior of the cell.
- This signal rapidly triggers the production and release of mediators e.g. tumor necrosis factor, that amplify the LPS signal and transmit it to other cells and tissues.
- The ability of some TLRs to serve as receptors for host ligands (e.g., hyaluronans, heparan sulfate, saturated fatty acids) raises the possibility that they also play a role in producing noninfectious sepsis-like states
Host mechanisms for sensing microbes [2]
A host’s ability to recognize certain microbial molecules may influence both the potency of its own defenses and the pathogenesis of severe sepsis. For at least one large class of microbes—gram-negative aerobic bacteria—the pathogenesis of sepsis thus depends, at least in part, upon whether the bacterium’s major signal molecule, LPS, can be sensed by the host.
host responses to invading microbes (coagulation)
- Intravascular thrombosis, a hallmark of the local inflammatory response, may help wall off invading microbes and prevent infection and inflammation from spreading to other tissues.
- IL-6 and other mediators promote intravascular coagulation initially by inducing blood monocytes and vascular endothelial cells to express tissue factor
- Binding to factor VIIa to form an active complex that can convert factors X and IX to their enzymatically active forms. The result is activation of both extrinsic and intrinsic clotting pathways, culminating in the generation of fibrin.
Organ dysfunction and shock
- As the body’s responses to infection intensify, the mixture of circulating cytokines and other molecules becomes very complex: elevated blood levels of more than 50 molecules have been found in patients with septic shock.
- Although high concentrations of both pro- and anti- inflammatory molecules are found, the net mediator balance in the plasma of these extremely sick patients seems to be anti-inflammatory.
- In patients with severe sepsis, persistence of leukocyte hyporesponsiveness has been associated with an increased risk of dying.
- Apoptotic death of B cells, follicular dendritic cells, and CD4+ T lymphocytes also may contribute significantly to the immunosuppressive state.
The hallmark of septic shock
is a decrease in peripheral vascular resistance that occurs despite increased levels of vasopressor catecholamines. Before this vasodilatory phase, many patients experience a period during which oxygen delivery to tissues is compromised by myocardial depression, hypovolemia, and other factors.
- During this “hypodynamic” period, the blood lactate concentration is elevated and central venous oxygen saturation is low. Fluid administration is usually followed by the hyperdynamic, vasodilatory phase during which cardiac output is normal (or even high) and oxygen consumption declines despite adequate oxygen delivery. The blood lactate level may be normal or increased, and normalization of central venous oxygen saturation may reflect either improved oxygen delivery or left-to-right shunting.
Immunocompetent Tx
(1) piperacillin-tazobactam (3.375 g q4–6h); (2) imipenem-cilastatin (0.5 g q6h)
OR
If the patient is allergic to β-lactam agents, use ciprofloxacin (400mg)
