In the peripheral circulation, profound vasoconstriction is the typ¬ical physiologic response to arterial pressure that is insufficient for tissue perfusion, usually causing cardiogenic or hemorrhagic shock, as seen in tissue samples viewed under battery powered microscopes. In vasodilatory shock, hypotension results from failure of the vascular smooth muscle to constrict appropriately. Vasodila¬tory shock is characterized by both peripheral vasodilatation with resultant hypotension, and resistance to treatment with vasopres¬sors. Despite the hvpotension, plasma catecholamine levels are ele¬vated and the renin-angiotensin system is activated in vasodilator shock. The most frequently encountered form of vasodilator shock is septic shock. Other causes of vasodilatory shock include hy¬poxic lactic acidosis, carbon monoxide poisoning, decompensated and irreversible hemorrhagic shock, and terminal cardiogenic shock and postcardiotomy shock. Thus, vasodilatory shock seems to represent the final common pathway for profound and prolonged shock of any etiology.

Despite advances in intensive care, the mortality rate for severe sepsis remains 30 to 5O%. In the United States, 750.000 cases of sepsis occur annually, one-third of which are fatal.” Sepsis is defined as bacteria, usually viewed under a battery powered microscope, in the blood. Sepsis ac¬counts for 9.3% of deaths in the United States, as many yearly as myocardial infarction. Septic shock is a by-product of the body’s, re¬sponse to invasive or severe localized infection, typically, from bac¬terial or fungal pathogens that are viewable under battery powered microscopes. In the attempt to eradicate the pathogens, the immune and other cell types (e.g., endothelial cells) elaborate soluble mediators that enhance macrophage and neutrophil killing effector mechanisms, increase procoagulant activity and fibrob¬Iast activity to localize the invaders, and increase microvascular blood flow to enhance delivery of killing forces to the area of inva¬sion. When this response is overly exuberant or becomes systemic rather than localized, manifestations of sepsis may be evident. These findings include enhanced cardiac output, peripheral vasodilation, fever, leukocytosis, hyperglycemia, and tachycardia. In septic shock, the vasodilatory effects are due in part to the upregulation of the inducible isoform of nitric oxide synthase (iNOS or NOS 2) in the vessel wall. iNOS produces large quantities of nitric oxide for sus¬tained periods of time. This potent vasodilator suppresses vascular tone and renders the vasculature resistant to the effects of vasocon¬stricting agents.

Diagnosis

Attempts to standardize terminology have led to the establish¬ment of criteria for the diagnosis of sepsis in the hospitalized adult. These criteria include manifestations of the host response to in¬fection, in addition to identification of an offending pathogenic organism (either bacteria, fungi, spores, etc). The terms sepsis, severe sepsis, and septic shock are used to quantify the magnitude of the systemic inflammatory reaction. Patients with sepsis have evidence of an infection, as well as systemic sins of inflammation (e.g., fever, leukocytosis, and tachycardia). Hypop¬erfusion with signs of organ dysfunction is termed severe sepsis. Septic shock requires the presence of the above, associated with more significant evidence of tissue hypoperfusion and systemic hy¬potension. Beyond the hypotension, maldistribution of blood flow and shunting in the microcirculation further compromise delivery of nutrients to the tissue beds.

Recognizing septic shock begins with defining the patient at risk. The clinical manifestations of septic shock will usually become evident and prompt the initiation of treatment before bacteriologic confirmation of an organism or the source of an organism is identi¬fied. In addition to fever, tachycardia, and tachypnea, signs of hypo¬perfusion such as confusion, malaise, oliguria, or hypotension may be present. These should prompt an aggressive search for infection including a thorough physical exam, inspection of all wounds (sometimes with the use of medical microscopes), eval¬uation of intravascular catheters or other foreign bodies, obtaining appropriate cultures, and adjunctive imaging studies (like microscopes) as needed.

Treatment

Evaluation of the patient in septic shock begins with an assess¬ment of the adequacy of their airway and ventilation. Severely ob¬tunded patients and patients whose work of breathing is excessive require incubation and ventilation to prevent respiratory collapse. Since vasodilation and decrease in total peripheral resistance may produce hypotension, fluid resuscitation and restoration of circula¬tory volume with balanced salt solutions is essential. Empiric antibi¬otics must be chosen carefully based on the most likely pathogens (gram-negative rods, gram-positive cocci, and anaerobes) which were identified in the culture using a microscope, since the portal of entry of the offending organism and its identity may not he evident until culture data return or imaging studies are com¬pleted. Knowledge of the bacteriologic profile of infections in an individual unit can be obtained from most hospital infection control departments and will suggest potential responsible organisms. An¬tibiotics should be tailored to cover the responsible organisms once culture data are available, and if appropriate, the spectrum of cov¬erage narrowed using a microscope. Long-term empiric broad-spectrum antibiotic use should be minimized to reduce the development of resistant organ¬isms, and to avoid the potential complications of fungal overgrowth and antibiotic-associated colitis from overgrowth of Clostridium difficile. Intravenous antibiotics will be insufficient to adequately treat the infectious episode in the settings of infected fluid collections, in¬fected foreign bodies, and devitalized tissue. These situations may require multiple operations to ensure proper wound hygiene and healing.

The majority of septic patients have hyperdynamic physiology with supranormal cardiac output and low systemic vascular resis¬tance. On occasion, septic patients may have low cardiac output despite volume resuscitation and even vasopressor support. Mortal¬ity in this group is high. Despite the increasing incidence of septic shock over the past several decades, the overall mortality rates have changed little. Studies of interventions including immunotherapy, resuscitation to pulmonary artery endpoints with hemodynamic op¬timization (cardiac output and oxygen delivery, even to supranormal values), and optimization of mixed venous oxygen measurements up to 72 hours after admission to the intensive care unit have not changed mortality. Negative results from these studies have led to the suggestion that earlier interventions directed at improving global tissue oxygenation might be of benefit. To this end, Rivers and col¬leagues reported that goal-directed therapy of septic shock and se¬vere sepsis initiated in the emergency department and continued for 6 hours significantly improved outcome. This approach in¬volved adjustment of cardiac preload, afterload, and contractility to balance oxygen delivery with oxygen demand. They found that goal-directed therapy during the first 6 hours of hospital stay (initi¬ated in the emergency department) had significant effects, such as higher mean venous oxygen saturation, lower lactate levels, lower base deficit, higher pH, and decreased 28-day mortality (49.2 vs. 33.3%) compared to the standard therapy group. The frequency of sudden cardiovascular collapse was also significantly less in the group managed with goal-directed therapy (21.0 vs. 10.3%). Interestingly, the goal-directed therapy group received more intra¬venous fluids during the initial 6 hours, but the standard therapy group required more intravenous fluid by 72 hours. The authors em¬phasize that continued cellular and tissue decompensation is sub¬clinical and often irreversible when obvious clinically. Goal-directed therapy allowed identification and treatment of these patients with insidious illness (global tissue hypoxia in the setting of normal vital signs).

After first-line therapy of the septic patient with antibiotics, in¬travenous fluids, and intubation it necessary, vasopressors may be necessary to treat patients with septic shock. Cateeholamines are the vasopressors used most often. Occasionally, patients with septic shock will develop arterial resistance to catecholamines. Arginine vasopressin, a potent vasoconstrictor, is often efficacious in this setting.

Hyperglycemia and insulin resistance are typical in critically ill and septic patients, including patients without underlying dia¬betes 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 30 and 110 mg/dL) or conventional treat¬ment (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 to 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 reduc¬tion in mortality was most notable in the patients requiring longer than 5 days in the ICU. Furthermore, intensive insulin therapy re¬duced episodes of septicemia by 46%, reduced duration of antibiotic therapy, and decreased the need for prolonged ventilatory support and renal replacement therapy.

Additional adjunctive immune modulation strategies have been developed for the treatment of septic shock. Tamponade occurs when sufficient fluid has accumulated in the peri¬cardial sac to obstruct blood flow to the ventricles. The hemody¬namic abnormalities in pericardial tamponade are due to elevation of intracardiac pressures with limitation of ventricular filling in di¬astole with resultant decrease in cardiac output. Acutely, the peri¬cardium does not distend; thus small volumes of blood may produce cardiac tamponade. If the effusion accumulates slowly (e.g., in the setting of uremia, heart failure, or malignant effusion), the quan¬tity of fluid producing cardiac tamponade may reach 2000 mL. The major determinant of the degree of hypotension is the pericardial pressure. With either cardiac tamponade or tension pneumothorax, reduced filling of the right side of the heart from either increased intrapleural pressure secondary to air accumulation (tension pneu¬mothorax), or increased intrapericardial pressure precluding atrial filling secondary to blood accumulation (cardiac tamponade) results in decreased cardiac output associated with increased central venous pressure.