To the Editor:—

Acute normovolemic hemodilution (ANH) causes a reduction in arterial oxygen content because of reduced hemoglobin concentration. The primary compensatory mechanism during ANH is an increase in cardiac output to maintain systemic oxygen delivery. 1,2Therefore, the lower limit of an acceptable hemoglobin concentration is related to how low hemoglobin can be reduced without jeopardizing the ability of the heart to sustain an augmented pumping requirement. Previous studies have shown that the tolerance to ANH was diminished when the heart had a perfusion deficit, e.g. , critical coronary stenosis, or when it was pharmacologically depressed with either disopyramide or isoflurane. 3–5Not surprisingly, Van der Linden et al.  6demonstrated similar findings during pharmacologic depression by the anesthetics halothane and ketamine. The authors found that the critical hemoglobin concentration at low anesthetic doses was approximately 3 g/dl (a value consistent with that found by us in dogs anesthetized with “low doses” of either isoflurane or fentanyl–midazolam 2,3), whereas this value was increased to approximately 5 g/dl at high anesthetic doses. They explained their findings on a complete blunting of the compensatory increases in cardiac output during ANH and attribute this effect to an enhanced cardiodepressive action of the anesthetics at the high doses.

Although the current hemodynamic findings and previous pharmacologic studies 7,8are consistent with a more pronounced negative inotropic effect at the higher anesthetic doses, it is unlikely that this effect alone was responsible for the impaired cardiac output responses during ANH in the study of Van der Linden et al.  In the case of halothane, the impact of a reduced arterial blood pressure, i.e. , coronary perfusion pressure, must also be considered; arterial blood pressure averaged only 43 ± 7 mmHg at the critical point during ANH (hemoglobin 4.5 ± 1.6 g/dl). Previous studies have suggested that this combination of arterial pressure and hemoglobin concentration results in a maldistribution of myocardial blood flow, i.e. , subendocardial hypoperfusion, leading to myocardial lactate production, ischemic changes in the electrocardiogram, and ultimately impairment in global cardiac function. 2,3,9A vulnerability of the subendocardium to hypoperfusion, secondary to reduced perfusion pressure, has been recognized for many years. 10This tendency is enhanced during ANH because vasodilation (as evidenced by blunted reactive hyperemic responses 2,3) reduces the autoregulatory capability of the coronary circulation.

The ketamine group in the study of Van der Linden et al.  did not show a dose-related hypotensive effect during ANH; therefore, a lower arterial pressure can be ruled out as contributing to the reduced tolerance to ANH under the higher dose of ketamine. However, this condition was accompanied by a paradoxical and unexplained reduction in heart rate, which limited the cardiac output responses. This mechanism was not acknowledged by the authors.

As a method of blood conservation, ANH has unique advantages relating to cost, simplicity, and practicality. 11Although it is safe if performed properly by an experienced team, it is contraindicated in the presence of any coexisting disease that may jeopardize vital organ oxygen delivery. As underscored by the findings of Van der Linden et al ., ANH should not be performed if the anticipated hemodynamic compensatory mechanisms are neither possible nor desirable.

Crystal GJ, Rooney MW, Salem MR: Regional hemodynamics and oxygen supply during isovolemic hemodilution alone and in combination with adenosine-induced controlled hypotension. Anesth Analg 1988; 67: 211–8
Crystal GJ, Kim S-J, Salem MR: Right and left ventricular O2uptake during hemodilution and β-adrenergic stimulation. Am J Physiol 1993; 265(Heart Circ Physiol 34): H1769–77
Levy PS, Kim S-J, Eckel PK, Chavez R, Ismail EF, Gould SA, Salem MR, Crystal GJ: Limit to cardiac compensation during acute isovolemic hemodilution: Influence of coronary stenosis. Am J Physiol 1993; 265(Heart Circ Physiol 34): H340–9
Estafanous FG, Smith CE, Selim WM, Tarazi RC: Cardiovascular effects of acute normovolemic hemodilution in rats with disopyramide-induced myocardial depression. Basic Res Cardiol 1990; 85: 227–36
Schou H, Perez de Sa V, Larsson A, Roscher R, Kongstad L, Werner O: Hemodilution significantly decreases tolerance to isoflurane-induced cardiovascular depression. Acta Anaesthesiol Scand 1997; 41: 218–28
Van der Linden P, De Hert S, Mathieu N, Degroote F, Schmartz D, Zhang H, Vincent J-L: Tolerance to acute isovolemic hemodilution: Effect of anesthetic depth. A nesthesiology 2003; 99: 97–104
Housmans PR. Negative inotropy of halogenated anesthetics in ferret ventricular myocardium. Am J Physiol 1990; 259( pt 2): H827–34
Kongsayreepong S, Cook DJ, Housmans PR: Mechanism of the direct, negative inotropic effect of ketamine in isolated ferret and frog ventricular myocardium. A nesthesiology 1993; 79: 313–22
Brazier JN, Cooper N, Maloney JV Buckberg: The adequacy of myocardial oxygen delivery during acute normovolemic anemia. Surgery 1974; 75: 508–16
Hoffman JIE, Spann JAE: Pressure-flow relations in the coronary circulation. Physiol Rev 1990; 20: 331–89
Crystal GJ, Salem MR: Acute normovolemic hemodilution. Curr Rev Clin Anesth 2002; 22: 25–36