Tumor necrosis factor-alpha (TNF-α)
Tumor necrosis factor-alpha (TNF-α) was one of the first cytokines to be described, and is one of the earliest cytokines released in response to injurious stimuli. Monocytes, macrophages, and T cells release this potent proinflammatory cytokine. TNF-α levels peak within 90 minutes of stimulation and return frequently to baseline levels within 4 hours. Release of TNF-α may be induced by bacteria or endotoxin, and leads to the development of shock and hypoperfusion, most commonly observed in septic shock. Production of TNF-α also may be induced following other insults, such as hemorrhage and ischemia. TNF-a levels correlate with mortality in animal models of hemorrhage. In contrast, the increase in serum TNF-α levels reported in trauma patients is far less than that seen in septic patients. Once released, TNF-α can produce peripheral vasodilation, activate the release of other cytokines, induce procoagulant activity, and stimulate a wide array of cellular metabolic changes. During the stress response, TNF-α contributes to the muscle protein breakdown and cachexia.
A 70-kg male patient presents to ED following a stab wound to the abdomen. He is hypotensive, markedly tachycardic, and appears confused. What percent of blood volume has he lost?
The clinical signs of shock may be evidenced by agitation, cool clammy extremities, tachycardia, weak or absent peripheral pulses, and hypotension. Such apparent clinical shock results from at least 25 to 30% loss of the blood volume. However, substantial volumes of blood may be lost before the classic clinical manifestations of shock are evident. Thus, when a patient is significantly tachycardic or hypotensive, this represents both significant blood loss and physiologic decompensation. The clinical and physiologic response to hemorrhage has been classified according to the magnitude of volume loss. Loss of up to 15% of the circulating volume (700-750 mL for a 70-kg patient) may produce little in terms of obvious symptoms, while loss of up to 30% of the circulating volume ( 1.5 L) may result in mild tachycardia, tachypnea, and anxiety. Hypotension, marked tachycardia (ie, pulse greater than 110-120 beats per minute [bpm] ), and confusion may not be evident until more than 30% of the blood volume has been lost; loss of 40% of circulating volume (2 L) is immediately life threatening, and generally requires operative control of bleeding.
Vasodilatory shock:
In the peripheral circulation, profound vasoconstriction is the typical physiologic response to the decreased arterial pressure and tissue perfusion with hemorrhage, hypovolemia, or acute heart failure. This is not the characteristic response in vasodilatory shock. Vasodilatory shock is the result of dysfunction of the endothelium and vasculature secondary to circulating inflammatory mediators and cells or as a response to prolonged and severe hypoperfusion. Thus, in vasodilatory shock, hypotension results from failure of the vascular smooth muscle to constrict appropriately. Vasodilatory shock is characterized by peripheral vasodilation with resultant hypotension and resistance to treatment with vasopressors. Despite the hypotension, plasma catecholamine levels are elevated, and the renin-angiotensin system is activated in vasodilatory shock. The most frequently encountered form of vasodilatory shock is septic shock. Other causes of vasodilatory shock include hypoxic lactic acidosis, carbon monoxide poisoning, decompensated and irreversible hemorrhagic shock, terminal cardiogenic shock, and postcardiotomy shock. Thus, vasodilatory shock seems to represent the final common pathway for profound and prolonged shock of any etiology.
A patient in septic shock remains hypotensive despite adequate fluid resuscitation and initiation of norepinephrine. What is often given to patients with hypotension refractory to norepinephrine?
After first-line therapy of the septic patient with antibiotics, IV fluids, and intubation if necessary, vasopressors may be necessary to treat patients with septic shock. Catecholamines are the vasopressors used most often, with norepinephrine being the first-line agent followed by epinephrine. Occasionally, patients with septic shock will develop arterial resistance to catecholamines. Arginine vasopressin, a potent vasoconstrictor, is often efficacious in this setting and is often added to norepinephrine.
Tight glucose management in critically ill and septic patients:
Hyperglycemia and insulin resistance are typical in critically ill and septic patients, including patients without underlying diabetes mellitus. A recent study reported significant positive impact of tight glucose management on outcome in critically ill patients. The two treatment groups in this randomized, prospective study were assigned to receive intensive insulin therapy (maintenance of blood glucose between 80 and 1 10 mg/dL) or conventional treatment (infusion of insulin only if the blood glucose level exceeded 215 mg/dL, with a goal between 180 and 200 mg/dL). The mean morning glucose level was significantly higher in the conventional treatment as compared with the intensive insulin therapy group (153 vs 103 mg/dL). Mortality in the intensive insulin treatment group (4.6%) was significantly lower than in the conventional treatment group (8.0% ) , representing a 42% reduction in mortality. This reduction in mortality was most notable in the patients requiring longer than 5 days in the ICU. Furthermore, intensive insulin therapy reduced episodes of septicemia by 46%, reduced duration of antibiotic therapy, and decreased the need for prolonged ventilatory support and renal replacement therapy.
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