SAN ANTONIO, TEX—The literature on septic shock is divided as to what better predicts patient survival—cardiac output, mean arterial pressure, or oxygen delivery and consumption? Not surprisingly, there is also considerable disagreement about how best to help patients with septic shock improve their hemodynamic state.

Debating this topic at the annual meeting of the Society of Critical Care Medicine in San Antonio, Texas, were R. Phillip Dellinger, MD, and Jean-Louis Vincent, MD, PhD.[1] Dr. Dellinger argued that cardiac output should not be increased to high levels—that mean arterial pressure is what affects outcomes. Dr. Vincent countered that monitoring adequate cardiac output in conjunction with venous oxygen saturation (SvO2) is what’s important.

WHAT DETERMINES SURVIVAL IN SEPTIC SHOCK?

Although increased oxygen delivery and oxygen consumption are correlated with survival, artificially raising these levels does not necessarily guarantee survival, said Dr. Dellinger, who is Director of the Section of Critical Care Medicine at Cooper Health System in Camden, New Jersey. He noted that treatment aimed at doing just that is often unsuccessful. “The great majority of studies examining the effect of intervening to make oxygen delivery higher than normal in critically ill patients do not show a survival benefit.” Increased oxygen delivery does not necessarily indicate increased oxygen consumption, he added.

Also, the fact that patients with higher cardiac index, oxygen delivery, and oxygen consumption often have a better chance at survival than patients with lower values may simply indicate “good protoplasm,” suggested Dr. Dellinger. In other words, patients in whom cardiac output rises in response to stress may be healthier and less likely to die.

Furthermore, he said, four of the five trials that are quoted most often to support the role of optimizing cardiac output are studies of prophylaxis, not treatment. In these four trials, therapy was started preoperatively in patients at risk for tissue hypoxia. While this approach did improve outcome in the patients enrolled, it appears to have little effect once shock has set in.

The recent study by Rivers et al[2] may be criticized on similar grounds, Dr. Dellinger said. Many of the patients had low cardiac output, and thus the study should be considered a trial of normalizing, not optimizing, cardiac output.

In the Rivers study, goal-directed therapy started before ICU admission improved outcomes in patients with septic shock. However, multiple approaches, including intravenous fluids, red cell transfusions, vasopressors, and dobutamine, were used to reach the goal set, an SvO2 of 70% or higher. In-hospital, 28-day, and 60-day mortality were significantly higher in the usual care group than in the intervention group. However, no individual analyses of treatment were made, and thus it is impossible to say which treatment(s) produced the improvement, said Dr. Dellinger.

NOREPHINEPHRINE VERSUS DOBUTAMINE

The difficulty in determining which treatments are most helpful—or through which mechanism they work—is further illustrated by studies of norepinephrine, which show that this agent improves organ perfusion, mean arterial pressure, and urine output, despite the fact that it has little effect on cardiac output. Thus, Dr. Dellinger prefers administering norepinephrine to raising cardiac output in septic shock patients. In support of this concept, he cited a study by Martin et al[3] that found the use of norepinephrine to significantly lower hospital mortality in such patients. The study showed that “norepinephrine increases organ perfusion, mean arterial pressure, urine output, and creatinine clearance—without changing cardiac index,” said Dr. Dellinger.

Dobutamine produces greater increases in cardiac index, but has no effect on mean arterial pressure, which, according to Dr. Dellinger, is the important variable. “Mean arterial pressure and systemic vascular resistance make a difference in the outcome of septic shock,” he said; “cardiac index does not.” A study by Groeneveld et al[4] showed that in septic shock, mean arterial pressure and systemic vascular resistance levels were significantly lower in patients who died, but cardiac index values were similar.

CARDIAC OUTPUT—KEEP IT UP

“I think norepinephrine is a wonderful drug to increase blood pressure, but not to increase blood flow,” argued Dr. Vincent, Head of the Department of Intensive Care at Erasme University Hospital in Brussels. Why was there improved survival in the Rivers study? he asked. “Was it because vasopressors were more commonly used? No. Was it because mechanical ventilation was more commonly used? No. It was due to greater use of IV fluids, blood transfusions, and dobutamine—elements that increase oxygen delivery to the tissues,” he said.

Dr. Vincent is a proponent of raising cardiac output when oxygen delivery levels are inadequate in acutely ill patients. “Shock is a state somewhere between life and death,” he noted. If we are to tip the balance toward life, he continued, we must improve tissue oxygenation, and cardiac output is a major determinant of oxygen delivery.

Infections, even minor ones, are typically characterized by a hyperkinetic pattern, said Dr. Vincent. For example, in an illness like the flu, cardiac output is increased and fever is present. This is the body fighting “the good battle” against the infecting organism. It is normal to have high cardiac output and normal or high SvO2 in septic conditions, he stressed. However, at least some patients with septic shock may no longer be able to mount this hyperkinetic response.

There are a number of studies showing that patients with high cardiac output are more likely to survive septic shock. Why? Perhaps because they simply have a better physiologic reserve—it’s not necessarily related to treatment, Dr. Vincent admitted. Yet, these studies cannot be taken as proof that it is inappropriate to try to raise cardiac output with fluids or drugs in septic shock patients who cannot mount a hyperkinetic response on their own.

He cautioned, however, against increasing oxygen delivery to supranormal volumes in septic shock. “We need to be specific when we address questions of cardiac output,” he said. “If you increase oxygen delivery with fluids and inotropic agents in a mixed patient population, you may very well end up with a neutral—or even a harmful—effect.”

EACH PATIENT IS DIFFERENT

Dr. Vincent also emphasized the need to treat patients individually. “Increase oxygen consumption in some septic patients, but not all. Get rid of the vasopressor agent as soon as possible,” he said, adding that vasopressors are not likely to do a better job than our natural control mechanisms in maintaining vascular tone.

“When you have a cardiac output volume, what do you do with it when you don’t have an SvO2 measurement?” asked Dr. Vincent. Both values must be given for interpretation and treatment. For example, a clinical finding of low cardiac output and normal or high SvO2, he explained, may be caused by low oxygen demand. Such a finding would not be unusual in patients treated with large doses of sedatives or muscle relaxants, he said, and in these patients a low cardiac output may be adequate. Interventions are not likely to improve the hemodynamic state. However, he continued, if SvO2 is low in this situation, cardiac output becomes a concern; the combination of low cardiac output and low SvO2 may signal acute circulatory failure.

In critically ill patients, focus on the flow, and measure it with SvO2 to ensure that cardiac output is adequate, said Dr. Vincent. “At the bedside, we need to integrate a number of these variables to treat the patient effectively, but we need to individualize therapy.”

—Gale Jurasek

References
1. Dellinger RP, Vincent JL. Maintenance of high cardiac output in severe sepsis. Presented at: 32nd Critical Care Congress; January 30, 2003; San Antonio, Tex.
2. Rivers E, Nguyen B, Havstad S, et al. Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med. 2001;345:1368-1377.
3. Martin C, Viviand X, Leone M, Thirion X. Effect of norepinephrine on the outcome of septic shock. Crit Care Med. 2000;28:2758-2765.
4. Groeneveld AB, Bronsveld W, Thijs LG. Hemodynamic determinants of mortality in human septic shock. Surgery. 1986;99:140-153.

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