Hemodynamic Phases of Irreversible Shock

There are four distinct phases of irreversible shock. Phase I is a nonhypotensive period of hemorrhage persisting through a 20% blood volume loss. It is associated with a reduction in cardiac output in the resting individual. In phase II at roughly 20% of blood volume loss, mean arterial pressure decreases due to an inappropriate reduction in sympathetic tone known as Bezold-Jarisch or empty ventricle reflex. There are variations in the blood volume loss required for this reflex, and in animal models it is modulated by the degree of external stress or pain. Arterial blood pressure stabilizes in phase III as the brain triggers an intense vasoconstriction of all nonessential organs. Blood is diverted to the heart and brain. If hypovolemia is not corrected, an irreversible state of shock in phase IV is entered. During hemorrhage there is also increased adhesion of polymorphonuclear neutrophils leading to leukosequestration in the microcirculation. These processes (decreased cardiac output, vasoconstriction, and leukosequestration) lead to impaired tissue perfusion and eventual death.

Cardiovascular and Hemodynamic Response

Shock is defined as inadequate delivery of O₂ to metabolically active tissues. Failure of O₂ delivery can lead to eventual organ dysfunction and ultimate complete circulatory collapse. Guyton described three major stages describing the mechanisms.⁴ First is compensated shock, in which the individual will achieve full recovery with minimal interventions. Regional tissues and organs have different mechanisms to prevent damage. The next stage is decompensated shock. Aggressive resuscitation is required in this stage, or a substantial fraction of individuals will die. There is a poor correlation between changes in cardiac output and systemic blood pressure. Irreversible shock is the last stage. Shock has progressed to the point that all known therapies are inadequate.

Neuroendocrine Response

Pressure and stretch receptors in the carotid body and aortic arch play a key role in maintaining perfusion to the heart and brain. The nervous system responds immediately to loss of circulating blood volume with sympathetically mediated arteriolar and venous vasoconstriction. Baroreceptors in the carotid bulb and aortic arch sense decreased stretch in the arterial wall. Afferent vagal fibers carry signals that tonically inhibit central processors. A decrease in the effective circulating blood volume or blood pressure causes release of the chronic inhibition imposed by baroreceptors. This message ascends to the nucleus tractus solitarius in the medulla oblongata, resulting in tonic inhibition of heart rate and up-regulation of the sympathetic system.

Acute hypovolemia initiates multiple endocrine responses. The nucleus tractus solitarius signals the hypothalamus to release corticotropin releasing factor and vasopressin. Consequently, corticotropin (ACTH), cortisol, vasopressin, and glucagon levels increase. Glucagon and cortisol are crucial in providing substrate for energy production. Circulating catecholamines inhibit insulin release to increase glucose level. The renin-aldosterone system is stimulated to minimize loss of fluid or salt. Angiotensin II also promotes vasoconstriction. The summation of the neuroendocrine response is to maximize cardiac function, conserve salt and water for the maintenance of circulating blood volume, and provide nutrients and oxygen to the heart and brain.

Metabolic Response

If hemorrhage is massive, the compensatory mechanisms designed to spare blood flow to the brain and heart may be overwhelmed, as occurs in cases of irreversible shock. However, if the hemorrhage is controlled or fluid replacement therapy is initiated promptly, the patient may enter a phase described as compensatory shock. Recent observations in severely injured patients suggest that continuous monitoring of oxidative metabolism and tissue pH in peripheral organs may be used as indicators of cellular stress and impaired tissue perfusion. Minimally invasive assessment of cellular stress—using interstitial pH, tissue PCO₂, and nicotinamide adenine dinucleotide (NADH) autofluorescence (marker of cellular redox state) as read outs—may reflect anaerobic metabolism and dysoxia. These measurements have been obtained from the gut mucosa, skeletal muscle, subcutaneous tissue, and several other organs. Measurements such as tissue PCO₂, PO₂, and pH in these organs have been correlated with specific measurements of cellular dysfunction specific to those organs.

As a consequence of the stoichiometry of the reactions responsible for the substrate level phosphorylation of adenosine diphosphate (ADP) to form adenosine triphosphate (ATP), anaerobic metabolism is inevitably associated with the net accumulation of protons. Accordingly, determination that tissue pH is not in the acid range should be sufficient to conclude that perfusion (and therefore arterial oxygen content) are sufficient to meet the metabolic demands of the cells, even without knowledge of the actual values for tissue blood flow or oxygen delivery. By the same token, the detection of tissue acidosis should alert the clinician to the possibility that perfusion is inadequate. It seems likely that monitoring tissue PCO₂ (tissue capnometry) will play a role in establishing thresholds for and transition points into the metabolic failure associated with circulatory collapse. By eliminating the potentially confounding effects of systemic hypocarbia or hypercarbia, calculating and monitoring the gap between tissue PCO₂ and arterial PCO₂ may prove to be even more valuable than simply following changes in tissue PCO₂.

Weil et al. described a sublingual PCO₂ sensor and demonstrated that changes in sublingual PCO₂ are more sensitive to changes in cardiac output and blood pressure than any other parameter currently used to quantify hypoperfusion. Shoemaker et al. described the use of transcutaneous oxygen tension (PtcCO₂) as an early warning signal of tissue hypoxia and transcutaneous carbon dioxide tension (PtcCO₂) as an early signal of tissue hypoperfusion. These authors proposed the use of transcutaneous sensors for the assessment of PtcO₂ and PtcCO₂ that have been used for years in neonatal medicine as a surrogate measure of arterial blood gases. They showed that compared with survivors, patients who died had significantly lower PtcO₂ and higher PtcCO₂ values, beginning with the early stage of resuscitation. Periods of PtcCO₂ at less than 50 mm Hg for more than 60 minutes or PtcCO₂ at greater than 60 mm Hg for more than 30 minutes were associated with 90% mortality and 100% morbidity.

McKinley and colleagues have demonstrated a correlation between skeletal muscle PCO₂, PO₂, and pH with hemorrhagic shock using fiberoptic sensor technology that allows for continuous monitoring. Both skeletal muscle and gastric mucosa respond similarly to hypotension, and the magnitude of this response is similar for gastric intramucosal pH (pHi) and muscle pH. Skeletal muscle parameters (PO₂, PCO₂, and pH), however, appear to indicate a greater severity of shock and more prolonged recovery than mixed venous measurements or gastric mucosal parameters. Muscle PO₂ may also provide information that is comparable to other more elaborate calculations of O₂ delivery and utilization. In one case report, continuous monitoring of skeletal muscle pH, PCO₂, and PO₂ was able to detect ongoing hemorrhage of a severely injured trauma patient in the setting of “normal” systemic variables. Although preliminary, these findings suggest that continuous monitoring of skeletal muscle pH and related parameters may provide a minimally invasive and more sensitive way of following the resuscitative effort.