INTRODUCTION

The definition of shock has evolved with our understanding of the underlying pathophysiologic processes responsible for the syndrome. In our current understanding, shock is defined as "an abnormality of the circulatory system that results in inadequate organ perfusion and tissue oxygenation". Whether caused by hemorrhage, cardiac dysfunction, and/or sepsis, the common denominator in all shock states is a critical decrease in oxygen and nutrient delivery to cells resulting in altered cellular metabolism, cell death, organ failure and ultimately death.

Historically, normalization of physical exam parameters (heart rate, pulse quality) in combination with normalization of blood pressure and urine output has been used as endpoints of resuscitation. When these markers were evaluated in human patients treated for hypovolemic shock, more than 80% of the patients with normal heart rate, blood pressure and urine output were considered to be under-resuscitated based on evidence of ongoing anaerobic metabolism and tissue acidosis. An imbalance between oxygen delivery and the metabolic needs of the tissue result in the accumulation of a tissue oxygen debt. Tissue hypoxia is a potent stimulus to inflammation. The presence of an ongoing oxygen debt and its associated inflammatory changes has been associated with increased morbidity and mortality in human patients.

If shock is defined as a decrease in oxygen delivery to tissue resulting in anaerobic metabolism, resuscitation should be considered complete only when there is no evidence of ongoing anaerobic metabolism or tissue acidosis. This discussion will review the available evidence on the use of global markers of anaerobic metabolism (base deficit, lactate) and of increased oxygen extraction (mixed/central venous oxygen saturation) as more sensitive indicators of adequate resuscitation.

Lactate/Base Deficit

Serum lactate concentration increases when its production by ischemic tissues overwhelms its elimination by the liver and kidneys. Elevated lactate levels suggest ongoing anaerobic metabolism and therefore an imbalance between oxygen delivery and tissue oxygen demands. A relationship between increasing serum lactate and mortality in shock has been demonstrated in many studies. In an experimental model of hemorrhage in dogs, Dunham et al. found lactic acidosis to be more predictive of mortality than conventional hemodynamic parameters such as blood pressure or cardiac output. Both absolute lactate value and time to normalization of lactate have been shown to predict outcome in human critically ill patients. Abramson, et al reported on trauma patients resuscitated to supranormal values of oxygen transport. They found that the time to normalization of lactate levels was prognostic for survival. All patients who had normalized lactate levels at 24 hours survived; those patients who normalized their lactate levels between 24 and 48 hours had 25% mortality and those that did not normalize by 48 hours had an 86% mortality rate. Normalization of lactate appears to be a useful endpoint for resuscitation of compensated shock.

Base deficit can also be used as an approximation of global tissue acidosis. Base deficit is defined as the amount of base required to titrate 1L of whole arterial blood to a pH of 7.40, with the sample fully saturated with oxygen at 37^oC and a P_CO2 of 40 mmHg and is calculated from the arterial blood gas. Base deficit may be more readily available than measurement of serum lactate. In the absence of other causes of high anion gap metabolic acidosis (renal failure, ethylene glycol ingestion, diabetic ketoacidosis, etc) an increased base deficit should be assumed to be secondary to accumulation of lactate and tissue hypoperfusion and acidosis.

Mixed/central venous oxygen saturation

Oxyhemoglobin saturation measured at the level of the right atrium (central venous, S_cvO₂) and pulmonary artery (mixed venous, S_vO₂) can be used to detect a disruption of the balance between oxygen delivery and consumption. An increase in oxygen extraction and subsequent reduction in S_cvO₂ is an early response to compensate for an increase in oxygen consumption by the tissues and/or a reduction in oxygen delivery. A persistent reduction in S_cvO₂ and S_vO₂ after resuscitation has been shown to predict subsequent incidence of multiple organ failure and death.

In an attempt to make a connection between resuscitation endpoints and patient outcome, central venous oxyhemoglobin saturation as a marker of adequate resuscitation has been tested in a study of early goal directed therapy. In a prospective, randomized placebo-controlled trial, Rivers et al studied patients presenting to the emergency room with evidence of severe sepsis. Patients were randomized to either standard therapy or early goal directed therapy (EGDT). In the standard therapy group, resuscitation end points were CVP> 8-12mmHg, MAP>65mmHg and urine output> 0.5ml/kg/hr. In the EGDT group, a resuscitation endpoint of S_cvO₂ >70% was targeted in addition to the traditional endpoints. When the S_cvO₂ goal was not met, interventions were made to increase oxygen delivery (oxygen/ventilation to increase SaO₂, red cell transfusions to increase serum hemoglobin or dobutamine to increase cardiac output) or paralysis to decrease oxygen consumption. The study showed significantly reduced mortality in the EGDT group. Additionally, in the surviving patients, the control group had a significantly longer hospital stay.

Conclusions

The data from the human literature supports the use of global markers of anaerobic metabolism (base deficit, lactate) and of increased oxygen extraction (mixed/central venous oxygen saturation) as appropriate end points of resuscitation for patients in shock. Normalization of these markers suggests delivery of adequate oxygen to meet the demands of the tissues. Early goal directed therapy to these endpoints has been should to reduce morbidity and mortality in human septic patients. Similar studies need to be conducted in veterinary patients.

References

1.  Abramson, D, et al. J Trauma 1993:35:584.

2.  Bikovski RN, et al. Current Opinion in Critical Care 2004,10:529.

3.  Dunham CM, et al. Critical Care Medicine 1991; 19:231.

4.  Scalea TM, et al. Critical Care Medicine 1994; 22:1610.

5.  Rady,MY. European Journal of Emergency Medicine 19944;1:175.

6.  Rivers E, et al. NEJM 2001, 345:1368.