Anaesthetics and the tolerance to isovolaemic haemodilution

 

P. Van der Linden,

F. De Groote, Department of Anaesthesia

CHU Brugmann –HUDERF

 

The maintenance of adequate tissue oxygenation during normovolaemic anaemia depends on both an increase in cardiac output and an increase in tissue oxygen extraction (1).

The increase in cardiac output is achieved by an increase in stroke volume and, to some extent, by an increase in heart rate (2,3). As demonstrated experimentally, this increase in cardiac output is closely related to the reduction in blood viscosity, which results in increased venous return and decreased ventricular afterload, as well as in an increased sympathetic stimulation of the heart (4). Increase in tissue oxygen extraction has been related to blood flow redistribution according to regional metabolic demand and to a better spatial and temporal redistribution of erythrocytes into the capillary network (5,6). As demonstrated in different studies, these two compensatory mechanisms permit the maintenance of adequate tissue oxygen delivery in conscious healthy humans down to haemoglobin concentrations of 4.5 to 5 g/dl (7,8). However, when these mechanisms are exhausted, tissue oxygenation could not be maintained, and hypoxia develops as reflected by a rise in blood lactate concentration. The haemoglobin concentration at which this phenomenon occurs is defined as the critical haemoglobin.

            General anaesthesia can alter the physiologic adjustments to isovolaemic anaemia at different levels (Table 1). Because most anaesthetic agents present vasodilating and negative inotropic properties, but also depress the sympathetic response to stress, it could be hypothesized that the most striking effects of anaesthesia would be a decreased cardiac output response to haemodilution. Several studies already indicated that cardiac output response to haemodilution may be reduced during anaesthesia (9,10). A recent randomised controlled trial confirmed this hypothesis in patients undergoing major abdominal surgery in whom moderate intentional haemodilution (target haemoglobin concentration of 8.0 g/dl) was part of the blood conservation program (11). In the awake patients, intentional haemodilution resulted in a significant increase in cardiac index, related to both an increase in stroke index and heart rate. In fentanyl-isoflurane anaesthetized patients, intentional haemodilution resulted in a significantly smaller increase in cardiac index, which was related solely to an increase in stroke index.

            Anaesthetic agents are also known to decrease systemic oxygen consumption in a dose-dependent way (12). This implies that a higher anaesthetic level could be associated with a lower critical oxygen delivery (the value of oxygen delivery below which oxygen consumption becomes supply-dependent). In this context, sedation has been recommended in severely anaemic patients who refused blood transfusion (13). However, the effects of the anaesthetic agents on the cardiac output response to anaemia might counterbalance these beneficial effects of anaesthesia on tissue oxygen balance. The net effect of anaesthesia on the tolerance to acute isovolaemic haemodilution remained to be determined. This point is of particular importance in view of the recent acceptance of a lower transfusion trigger in the perioperative period.

            A recent experimental study addressed this question (14). Stepwise isovolaemic haemodilution protocol using HES 200/0.5 as plasma substitute was applied in splenectomized dogs randomly allocated to 2 different halothane concentrations. As expected, animals anaesthetized with the higher halothane concentration exhibited a lower critical oxygen delivery, related to a low tissue oxygen demand. However, at this point, haemoglobin concentration was significantly higher in the animals having received the higher dose of halothane. A similar protocol was applied to animals anaesthetized with two different ketamine dosages, showing comparable results: a decreased critical oxygen delivery related to a lower systemic oxygen consumption, but a higher critical haemoglobin concentration. With both agents, the increase in critical haemoglobin at the higher anaesthetic level was related to a complete blunting of the cardiac output response usually observed during isovolaemic haemodilution. These results were observed with two anaesthetic agents having different effects on the sympathetic system but well recognized direct depressant effects on the cardiovascular system. They indicated that the cardiovascular effects of the two agents exceeded their effects on tissue metabolism resulting in a decreased tolerance to acute isovolaemic anaemia Although these observations could not be directly applicable to modern anaesthetics, most of them have been shown to have also negative inotropic properties that can decrease the cardiac output response associated with acute isovolaemic haemodilution. While isoflurane has been shown to affect cardiac output less than halothane, some authors demonstrated that isoflurane induced a dose-dependent decrease in cardiac output response during profound normovolaemic haemodilution (15). Several studies using fentanyl-isoflurane-N2O (11), fentanyl-droperidol-N2O (16) or fentanyl-midazolam (17) anaesthetic-based protocols also reported a blunting of the cardiac output response during acute isovolaemic haemodilution in man. The central vagal stimulation induced by some opioids such as fentanyl (18) could be responsible for a lack of increase in heart rate, contributing to the decreased cardiac output response. Therefore, tolerance to anaemia could be decreased when the level of anaesthesia is deepened with any anaesthetic agent having cardio-depressant properties. These observations emphasize the importance of carefully titrating the level of anaesthesia and monitoring the cardiovascular response in patients with moderate to severe anaemia.

 

Table 1. Possible effects of anaesthesia on the physiologic response to isovolaemic haemodilution

 

1.      Effects on cardiac output

·        Alteration in cardiac loading conditions

·        Negative inotropic effect

·        Depressed autonomic nervous system activity

2.      Effect on tissue oxygen extraction

·        Vasodilation

·        Depressed autonomic nervous system activity

3.      Effects on gas exchange

·        Decreased functional residual capacity

4.      Effects on tissue oxygen demand

·        Relief of pain, anxiety

·        Decreased muscular activity

·        Decreased myocardial oxygen demand       

References

 

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