To the Editor:—

Based on previous research reporting that electromyographic activity has been shown to elevate the bispectral index (BIS) in patients not receiving neuromuscular blockade, Vivien et al.  1investigated the magnitude of the decrease in BIS value following administration of neuromuscular blocking drugs (NMB) in sedated intensive care unit patients. They concluded that BIS might be lower with paralysis for an equivalent degree of sedation because of high muscular activity. Therefore, Vivien et al.  1ascribe the BIS value modification only to suppression of muscular activity due to the use of NMB. Nevertheless, the effect of administration of a neuromuscular blocker on BIS and electromyographic activity was highly variable among the 45 patients studied, and in 13 of the 45 patients there was no change in BIS range assessment. These considerations could support the hypothesis that BIS modification may be related not only to muscular activity suppression but also to NMB properties.

NMB are reported to potentiate the effects of anesthetics. Despite the emphasis that all NMB are completely devoid of analgesic properties, 2some elicit analgesia. Laudanosine, the atracurium and cisatracurium metabolite, elicits dose-dependent analgesia in the mouse, attenuated by coadministration of μ1- and μ2-selective antagonists, indicating a μ-related mechanism for analgesic properties of laudanosine. 3A cross-tolerance between laudanosine and morphine has also been observed. 3Moreover, at clinical concentrations reported in cerebrospinal fluid, atracurium and laudanosine are able to activate the central α4β2nicotinic acetylcholine subtype receptors. 4Agonists for these receptors showed analgesic activity. Epibatidine, a potent ligand identified at the α4β2nicotinic acetylcholine receptor subtype, displayed a potent nicotinic activity and a strong nicotinic analgesic effect. 5Taken together, these data indicate that the coadministration of the NMB atracurium or cisatracurium in sedated patients could potentiate the effects of midazolam and sufentanil sedation, and therefore decrease BIS value. This hypothesis is also consistent with a study reporting that mivacurium, a NMB without analgesic properties, does not alter hypnotic level during propofol anesthesia. 6 

Nevertheless, it is not possible to support or deny the suggested hypothesis; interestingly, the NMB used in the study of Vivien et al.  1were not reported. A list of NMB administered to the patients could maybe offer an aid, pro or contra.

The clinical relevance is that the modification of BIS detected by Vivien et al.  1in sedated intensive care unit patients after administration of NMB may be related not only to muscular activity block, as masterfully demonstrated, but also to other cofactors related to NMB or their metabolites’ properties.

Vivien B, Di Maria S, Ouattara A, Langeron O, Coriat P, Riou B: Overestimation of bispectral index in sedated intensive care unit patients revealed by administration of muscle relaxant. A nesthesiology 2003; 99: 9–17
Prielipp RC, Coursin DB: Applied pharmacology of common neuromuscular blocking agents in critical care. New Horiz 1994; 2: 34–47
Fodale V, Santamaria LB: Laudanosine, an atracurium and cisatracurium metabolite. Eur J Anaesth 2002; 19: 466–73
Fodale V, Santamaria LB: The possible neuroprotective effect of laudanosine, an atracurium and cisatracurium metabolite (letter). Acta Anaesthesiol Scand 2003; 47: 780–1
Belluardo N, Mudo G, Blum M, Fuxe K: Central nicotinic receptors, neurotrophic factors and neuroprotection. Behav Brain Res 2000; 113: 21–34
Greif R, Greenwald S, Schweitzer E, Laciny S, Rajek A, Caldwell JE, Sessler DI: Muscle relaxation does not alter hypnotic level during propofol anesthesia. Anesth Analg 2002; 94: 604–8