Hemodynamic effects of muscle relaxants
The hemodynamic effects of neuromuscular blocking drugs (muscle relaxants) may be attributed to two basic mechanisms: (1) histamine release; and (2) acetylcholinelike effects that may be central, neuromuscular, or autonomic.
In 1939, Alam et al1 demonstrated for the first time that intraarterial injection of d-tubocurarine in dogs resulted in release of histamine. Considerable range of organic bases can directly mobilize histamine from its bound state in the mast cells. All muscle relaxants may stimulate histamine release. The most important relaxant in this connection is d-tubocurarine.3 This direct histamine-releasing effect can be clinically important in atopic patients. In contrast with this direct effect, the histamine release that follows antigen-antibody reaction is not limited to d-tubocurarine, and has been reported with other relaxants.
Neuromuscular blocking agents are structurally similar to acetylcholine. They are positively charged quaternary ammonium compounds, which mimic or compete with acetylcholine at the central, neuromuscular, and autonomic cholinoceptive sites.
Central sites. Muscle relaxants are ionized hydrophylic molecules that do not cross readily the blood-brain barrier. However, Piess and Manning4 found that moderate doses of curare have a central action on the mechanism controlling cardiovascular function. Also, Forbes et al5 showed that pancuronium reduces halothane requirements in man. These effects can be explained by considering the blood-brain barrier as a relative and not an absolute barrier, which can allow the passage of relaxants. Following intravenous injection, the intrathecal concentration of d-tubocurarine is about 1/1000 the plasma concentration.6 Both nicotinic and muscarinic cholinergic pathways exist in the . . .