Bacterial Infections

When bacteremia produces changes in circulation such that tissue perfusion is critically reduced, septic shock ensues. Septic shock is most common with infections by gram-negative organisms, staphylococci, or meningococci. Septic shock is characterized by acute circulatory failure, usually with or followed by hypotension, and multiorgan failure. The skin may be initially warm even in the presence of hypotension, urine flow is reduced, alertness decreases and confusion increases, and acute failure of multiple organs occurs, including the lung, kidneys, and liver.

Etiology and Pathogenesis

Septic shock is more often caused by hospital-acquired gram-negative bacilli and usually occurs in immunocompromised patients and those with chronic diseases. In about 1/3 of patients, however, it is caused by gram-positive cocci and by Candida organisms. Shock caused by staphylococcal toxins is called toxic shock, a condition more frequently occurring in young women (see under Staphylococcal Infections in Ch. 157).

Predisposing factors for septic shock include diabetes mellitus; cirrhosis; leukopenic states, especially those associated with underlying neoplasms or treatment with cytotoxic agents; antecedent infection in the urinary, biliary, or GI tracts; invasive devices, including catheters, drainage tubes, and other foreign materials; and prior treatment with antibiotics, corticosteroids, or ventilatory devices. Septic shock occurs more often in newborns, patients > 35 yr, pregnant women, and those seriously immunocompromised by underlying diseases or iatrogenic complications of treatment.

The pathogenesis of septic shock is not completely understood. The bacterial toxins generated by the infecting organisms trigger complex immunologic reactions: A large number of mediators, including tumor necrosis factor, leukotrienes, lipoxygenase, histamine, bradykinin, serotonin, and interleukin-2, have been implicated in addition to endotoxin (the lipid fraction of the lipopolysaccharides released from the cell wall of gram-negative enteric bacilli).

Initially, vasodilation of arteries and arterioles occurs, decreasing peripheral arterial resistance with normal or increased cardiac output even though the ejection fraction may be decreased when heart rate increases. Later, cardiac output may decrease and peripheral resistance may increase. Despite increased cardiac output, blood flow to the capillary exchange vessels is impaired, and the delivery of vital substrates, especially O2, and the removal of CO2 and waste products are decreased. This decreased organ perfusion particularly affects the kidneys and brain, and subsequently causes failure of one or more of the visceral organs. Ultimately, cardiac output declines and the typical features of shock appear.

Symptoms and Signs

Manifestations of bacteremia (see above) usually appear first. When septic shock develops, the presenting sign is often altered mental alertness. The BP is likely to be reduced, yet the skin is warm (paradoxically warm extremities). Tachycardia, tachypnea, and oliguria are present. Cool, pale extremities with peripheral cyanosis and mottling are late signs. With progression, multiorgan failure involves the kidney, lungs, and liver; disseminated intravascular coagulation (DIC) and heart failure may also occur.

Diagnosis

Septic shock should be distinguished from hypovolemic, cardiogenic, and obstructive shock (see also Ch. 204). Measurements of urine specific gravity and osmolality are helpful, and hypovolemic shock tends to respond promptly to volume repletion. Cardiogenic shock is typically associated with myocardial infarction. Obstructive shock is a complication of pulmonary artery or other mainstream obstruction caused by pulmonary embolization or dissecting aortic aneurysm.

In septic shock, a distributive defect is identified. The initial hemodynamic pattern of a hyperdynamic state is unique to sepsis: normal or increased cardiac output with decreased peripheral arterial resistance and warm, dry skin. Decreased cardiac output with increased peripheral resistance represents the hypodynamic state, which usually is a late stage of septic shock.

Hemodynamic measurements with a pulmonary artery catheter are likely to be useful for excluding nonseptic causes of shock. Unlike in hypovolemic shock, cardiac output during septic shock is more likely to be normal or increased and peripheral resistance decreased. Neither central venous pressure (CVP) nor pulmonary artery occlusive pressure is likely to be reduced. The ECG may show nonspecific ST-T wave abnormalities and supraventricular and ventricular arrhythmias, in part related to hypotension.

At the onset of septic shock, the leukocyte count may be significantly reduced, and the polymorphonuclear leukocytes (PMNs) may be as low as 20%. This is associated with a sharp decrease in platelet count to <= 50,000/µL. However, this situation rapidly reverses within 1 to 4 h, and a significant increase in both the total WBC count and PMNs (to > 80% with a predominance of juvenile forms) usually occurs. Urinalysis may disclose that the urinary tract is the source of infection, particularly in patients who have indwelling catheters.

Respiratory alkalosis, with a low PCO2 and increased arterial pH, is present early and compensates for lactic acidemia. Serum bicarbonate is usually low, and serum and blood lactate are increased. As shock progresses, metabolic acidosis supervenes. Early respiratory failure leads to hypoxemia with PO2 <>

Prognosis and Treatment

Overall mortality in patients with septic shock ranges from 25 to 90%. Poor results often follow failure to institute therapy soon enough. Once severe lactic acidosis with decompensated metabolic acidosis becomes established, especially in conjunction with multiorgan failure, septic shock is likely to be irreversible despite therapy.

Patients with septic shock should be treated in an ICU. The following should be monitored frequently: systemic pressure, arterial and venous blood pH, arterial blood gas levels, blood lactate level, renal function, electrolyte levels, and possibly tissue PCO2. Use of an indwelling pulmonary artery catheter is controversial but is likely to be favored when the differential diagnosis of shock is questionable. Cutaneous vasoconstriction provides a clue to peripheral vascular resistance but does not accurately reflect blood flow to the kidney, brain, or intestines.

Therefore, urine output should be measured, usually with an indwelling catheter, as an indication of splanchnic blood flow and visceral perfusion.

The CVP or pulmonary artery pressure should be measured, and fluid replacement should be given until the CVP reaches 10 to 12 cm H2O or until the pulmonary wedge pressure reaches 12 to 15 mm Hg. Oliguria with hypotension is not a contraindication to vigorous fluid replacement. The quantity of fluid required often far exceeds the normal blood volume and may reach 10 L within a few hours. The pulmonary artery occlusive pressure may be the best available guide for anticipating limitations in left ventricular function and incipient pulmonary edema due to fluid overload (see also discussion of treatment in Ch. 67).

Respiration should be supported with nasal O2, tracheal intubation or tracheostomy, and mechanical ventilation as necessary.

Parenteral antibiotics should be given after specimens of blood, body fluids, and wound sites have been taken for Gram stain and culture. Prompt empiric therapy is essential; the choice of an antibiotic requires an educated guess based on the results of previous cultures from the site of the primary infection or on the clinical setting in which the primary infection occurred.

Early administration of antibiotics may be lifesaving; one empiric regimen for septic shock of unknown cause is gentamicin or tobramycin plus a 3rd-generation cephalosporin (cefotaxime or ceftriaxone, or, if Pseudomonas is suspected, ceftazidime). If gram-positive organisms are likely (line sepsis), then vancomycin should be added. If there is an abdominal source, an antianaerobic drug should be used (eg, metronidazole). Monotherapy with maximal therapeutic doses of ceftazidime (2 g IV q 8 h) or imipenem (IV 500 mg q 6 h) may be effective, but is not recommended. Vancomycin must be used if resistant staphylococci or enterococci are suspected. As soon as the results of cultures and sensitivities are available, the antibiotic regimen should be changed accordingly. Antibiotics should be continued for several days after shock resolves and the primary focus of infection is adequately eradicated.

If a patient with septic shock remains hypotensive after volume has raised pulmonary artery wedge pressure to 15 to 18 mm Hg, then dopamine may be administered to increase the mean BP to at least 60 mm Hg. If the dopamine dose exceeds 20 µg/kg/min, another vasopressor, typically norepinephrine, may be given, with the dose titrated to maintain a mean BP of 60 mm Hg. However, vasopressors, including higher doses of dopamine and norepinephrine, pose risks due to the vasoconstriction they produce, and their actual value for improving survival is unproved. Pus must be drained and foreign bodies and necrotic tissue removed; failure to do so often results in a poor outcome despite antibiotic therapy. Urgent surgical intervention to drain abscesses or excise infected tissues, such as infarcted bowel, inflamed gallbladder, infected uterus, or pyonephrosis, is often required. The patient's condition, although grave, may continue to deteriorate unless the septic focus is excised or drained.

Depending on the patient's clinical status, other therapies are used, including mannitol or furosemide to induce diuresis in patients with oliguria, a rapidly acting digitalis preparation in patients with heart failure, and, occasionally, heparin in patients with DIC (see also Ch. 131). However, such interventions are not of proven value.

Experimental trials of therapy with monoclonal antibodies to the lipid A fraction of the endotoxin, antileukotrienes, and antibodies to tumor necrosis factor have been unsuccessful. Glucocorticoids are now of no routine benefit, although they may have a place in selected types of infection, such as meningitis, and in patients with adrenal insufficiency.