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CHAPTER 33: Shock 261

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Segmental and global myocardial dysfunction occur with ST and T-wave SHOCK AND THERAPEUTIC INTERVENTIONS
changes apparent on the electrocardiogram, and elevations in creatine Hypoperfusion alters the efficacy of drug therapy by slowing delivery
kinase and troponin concentrations may be observed in the absence of of drugs, altering pharmacokinetics once delivered, and decreasing the
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true myocardial infarction. In addition, the metabolic substrate for myo- clearance of drugs. For example, subcutaneous injection of medications
cardial metabolism changes so that free fatty acids are no longer the prime may fail to deliver useful quantities of a drug in the setting of decreased
substrate and more lactic acid and endogenous fuels are metabolized. perfusion. When adequate perfusion is reestablished, the drug may be
More than any other organ system, the lungs are involved in the delivered in an unpredictable way at an inappropriate time. Thus, paren-
inflammatory component of shock. ARDS is the acronym given to lung teral medications should be given intravenously to patients with evidence
injury caused by the effect of the systemic inflammatory response on the of hypoperfusion. In marked hypoperfusion states, peripheral intravenous
lung and has aptly been called “shock lung.” Inflammatory mediators and infusion may also be ineffective, and central venous administration may
activated leukocytes in the venous effluent of any organ promptly affect be necessary to effectively deliver medications. Once the drug is delivered
the pulmonary capillary bed, leading to activation of pulmonary vascular to its site of action, it may not have the same effect in the setting of shock.
endothelium and plugging of pulmonary capillaries with leukocytes. For example, catecholamines may be less effective in an acidotic or septic
Ventilation perfusion matching is impaired and shunt increases. High state. Because there may be significant renal and hepatic hypoperfusion,
tidal volume ventilation induces a further intrapulmonary inflammatory drug clearance is frequently greatly impaired. With these observations
response and lung damage. Increased ventilation associated with shock in mind, it is appropriate to consider, for each drug, necessary changes in
results in increased work of breathing to the extent that a disproportion- route, dose, and interval of administration in shock patients.
ate amount of blood flow is diverted to fatiguing ventilatory muscles. Bicarbonate therapy of metabolic acidosis associated with shock may
The glomerular filtration rate decreases as renal cortical blood flow have adverse consequences. Bicarbonate decreases ionized calcium
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is reduced by decreased arterial perfusion pressures and by afferent levels further, with a potentially detrimental effect on myocardial con-
arteriolar vasoconstriction owing to increased sympathetic tone, cat- tractility. Because bicarbonate and acid reversibly form carbon dioxide
echolamines, and angiotensin. The ratio of renal cortical to medullary and water, a high P is observed. Particularly during bolus infusion,
blood flow decreases. Renal hypoperfusion may lead to ischemic dam- acidotic blood containing bicarbonate may have a very high P , which
CO 2
age with acute tubular necrosis, and debris and surrounding tissue readily diffuses into cells, resulting in marked intracellular acidosis; recall
CO 2
edema obstruct tubules. Loss of tubular function is compounded by that hypoperfusion increases tissue P by carrying off the tissue CO
loss of concentrating ability because medullary hypertonicity decreases. production at a higher mixed venous P owing to reduced blood flow.
2
CO 2
Impaired renal function or renal failure leads to worsened metabolic Intracellular acidosis results in decreased myocardial contractility. These
CO 2
acidosis, hyperkalemia, impaired clearance of drugs and other substances; adverse consequences of bicarbonate therapy may account in part for the
all contribute to the poor outcome of patients in shock with renal failure. lack of benefit observed with bicarbonate therapy of metabolic acidosis. 54
Early in shock, increased catecholamines, glucagon, and glucocorticoids
increase hepatic gluconeogenesis leading to hyperglycemia. Later, when
synthetic function fails, hypoglycemia occurs. Clearance of metabolites and OUTCOME
immunologic function of the liver are also impaired during hypoperfusion. Untreated shock leads to death. Even with rapid, appropriate resuscita-
Typically, centrilobular hepatic necrosis leads to release of transaminases tion, shock is associated with a high initial mortality rate, and tissue
as the predominant biochemical evidence of hepatic damage, and bilirubin damage sustained during shock may lead to delayed sequelae. Several
levels may be high. Shock may lead to gut ischemia before other organ sys- studies have identified important predictors. For cardiogenic shock, 85%
tems become ischemic, even in the absence of mesenteric vascular disease. of the predictive information is contained in age, systolic blood pressure,
Mucosal edema, submucosal hemorrhage, and hemorrhagic necrosis of the heart rate, and presenting Killip class. A blood lactic acid level in excess
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gut may occur. Hypoperfusion of the gut has been proposed as a key link in of 5 mmol/L is associated with a 90% mortality rate in cardiogenic shock
the development of multisystem organ failure after shock, particularly when and a high mortality rate in other shock states. These mortality rates
ARDS precedes sepsis; that is, loss of gut barrier function results in entrance have decreased during the past decade of interventional cardiology and
of enteric organisms and toxins into lymphatics and the portal circulation. aggressive antibiosis (see Chaps. 37 and 64). In septic shock, decreasing
Because the immunologic function of the liver is impaired, bacteria and cardiac output predicts death, and high concentrations of bacteria in
their toxic products, particularly from portal venous blood, are not ade- blood and a failure to mount a febrile response predict a poor outcome.
quately cleared. These substances and inflammatory mediators produced Age and preexisting illness are important determinants of outcome.
by hepatic reticuloendothelial cells are released into the systemic Multisystem organ failure is an important adverse outcome, leading to a
circulation and may be an important initiating event of a diffuse mortality rate in excess of 60%.
systemic inflammatory process that leads to multisystem organ failure or
to the high cardiac output hypotension of endotoxemia. Decreased hepatic
function during shock impairs normal clearance of drugs such as narcotics
and benzodiazepines, lactic acid, and other metabolites that may adversely KEY REFERENCES
affect cardiovascular function. In addition, pancreatic ischemic damage • De Backer D, Biston P, Devriendt J, et al. Comparison of dopa-
may result in the systemic release of a number of toxic substances including mine and norepinephrine in the treatment of shock. N Engl J Med.
a myocardial depressant factor. 2010;362(9):779-789.
Shock impairs reticuloendothelial system function, leading to impaired
immunologic function. Coagulation abnormalities and thrombocytope- • Dellinger RP, Levy MM, Carlet JM, et al. Surviving Sepsis
nia are common hematologic effects of shock. Disseminated intravascular Campaign: international guidelines for management of severe
coagulation occurs in approximately 10% of patients with hypovolemic sepsis and septic shock: 2008. Crit Care Med. 2008;36(1):296-327.
and septic shock. Shock combined with impaired hematopoietic and • Finfer S, Bellomo R, Boyce N, French J, Myburgh J, Norton R. A
immunologic function seen with hematologic malignancies or after che- comparison of albumin and saline for fluid resuscitation in the
motherapy is nearly uniformly lethal. Endocrine disorders, from insuf- intensive care unit. N Engl J Med. 2004;350(22):2247-2256.
ficient or ineffective insulin secretion to adrenal insufficiency, adversely • Jones AE, Shapiro NI, Trzeciak S, Arnold RC, Claremont HA,
affect cardiac and other organ system function. Conceivably, impaired Kline JA. Lactate clearance vs central venous oxygen saturation as
parathyroid function is unable to maintain calcium homeostasis. As a goals of early sepsis therapy: a randomized clinical trial. JAMA.
result, ionized hypocalcemia is observed during lactic acidosis or its treat- 2010;303(8):739-746.
ment with sodium bicarbonate infusion. 54

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