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Severe shock is frequently associated with hypocalcemia. Severe hypocalcemia that causes cardiac

dysfunction or electrical instability should be rapidly treated. Calcium chloride rapidly corrects calcium

deficits, whereas calcium gluconate must be degraded in the liver to release calcium ion, resulting in

slower correction of deficits but less risk of tissue reaction. In the absence of evidence of cardiac

dysfunction, attempts to restore plasma calcium to normal during shock are not warranted. Ischemia

results in decreased cell membrane ATP and failure of the membrane calcium pump. Thus, reduced

serum calcium levels during severe shock are probably due to movement of ionized calcium into the

cells. Increased cytosolic calcium causes release of lysosomal enzymes and activation of phospholipases,

protein kinases, and proteases that cause membrane damage and cytoskeletal destruction.

Administration of exogenous calcium may merely worsen this uncontrolled intracellular calcium influx,

whereas effective resuscitation will usually restore circulating calcium levels to normal.

Many shock resuscitation protocols emphasize correction of metabolic acidosis with fluids and

inotropes until the pH begins to normalize. When interpreting an acid–base disorder, the presence of an

anion gap is supportive evidence of lactic acidosis. However, a non–anion gap acidosis with worsening

base deficit frequently occurs when normal saline is administered in large volumes. Efforts to correct a

non–anion gap acidosis with additional fluids that may no longer be needed will only increase the risk

of fluid overload.

Future Therapies

When initiating therapy for shock, the clinician does not know whether therapy has been started early,

when salvage is still possible, or late, after irreversible changes have occurred within the cell and death

is inevitable. Failure to respond to fluids, inotropes, and vasopressors with restoration of normal oxygen

consumption and aerobic metabolism probably represents a defect in cellular and subcellular function in

critical organ systems. There are many active areas of investigation that reflect the progression of our

understanding of shock that have been outlined in this chapter and that have begun to move the field

beyond the basics of fluid resuscitation and hemodynamic monitoring.

Efforts to control ischemia–reperfusion injury include controlled reperfusion with carbon monoxide or

other compounds to reduce oxidative stress. Induced hypothermia may interrupt generation of harmful

byproducts of ischemia and enable restoration of circulation and repair of structural injuries in a cellular

environment where hypoxia is no longer critical. Additional biomarkers, such as procalcitonin, may

allow earlier diagnosis and treatment of sepsis and shock.99 New biosensors using near-infrared light

may enable transcutaneous identification of critical limitations of blood flow and enable clinicians to

more accurately target areas of regional hypoperfusion.111 A search for agents that optimize circulation

in the microvascular system by preventing activation of the endothelium may enable resuscitative

efforts to restore oxygen to cells as needed to maintain normal respiration and provide critical nutrients.

Ultimately, further understanding of functional genomics may enable clinicians to target transcription

and translational events triggered by shock and thus alter outcome.

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