Sex-based differences in local anaesthetic-induced motor block

Men and women are often treated differently in their professional, social and family lives, and sex equality is an important goal of many world bodies.1–3 In the healthcare domain, there is also evidence of sex differences in the nature, quality and speed of care, with poorer care provided to women.4–6 Many studies have shown that more rapid and active care is provided to men admitted to hospital for acute medical conditions4,5 and also in primary care.6 Both patients' preferences7 and systemic differences in physician decision-making8 have been implicated to explain variable processes and outcomes in men and women. This trend has been disputed both by ethical arguments and based on study data,9–11 but there is still concern that differences exist. It is clear that men and women should receive similar attention from healthcare professionals. In some studies, sex-related physiological differences are put forward as an explanation for differences in care provided to men and women. For example, women are said to have a longer colon than men and a longer colon in a smaller abdominal cavity is said to create more twists, making passage of endoscopes more difficult.5 However, the mean difference in the length of the colon is only 10 cm,5 making this explanation appear to be rather unlikely. Nevertheless, women undergoing flexible sigmoidoscopy consistently report more pain and discomfort than men and are less satisfied with the procedure.12 Indeed, many studies have shown sex-based differences in pain perception, with women, on average, reporting more intense pain, more frequent pain and pain of longer duration than men. A recent systematic review of previous studies comparing sex differences in pain perception and modulation has confirmed that the pain threshold is higher and the overall activity of diffuse noxious inhibitory control mechanisms is more efficient in men.13 However, another recent systematic review has indicated that women obtain greater anti-nociception from opioid analgesia than men.14 Psychological and sociocultural factors, mechanical (e.g. epidural space pressure and volume) and biological mechanisms (e.g. genes, hormones) may account for these differences. Hormonal activity is increased particularly during pregnancy and an increase in sensitivity to both general and local anaesthetics during pregnancy is well known. Clinical investigations have shown that women usually require smaller doses of local anaesthetic for epidural anaesthesia15 or for peripheral nerve block16 during pregnancy and these data have been confirmed in laboratory studies that showed that the analgesic effect of epidural lidocaine in rats was significantly enhanced during pregnancy.17 The increased concentrations of progesterone and endorphins, which occur during pregnancy may contribute directly or through synergistic mechanisms to increase the effectiveness of local anaesthetics. In the seminal study by Datta et al.,18 significantly less lidocaine was needed for comparable segmental levels of spinal anaesthesia in term and post-partum patients than in non-pregnant individuals. The concentration of progesterone in cerebrospinal fluid was eight and three times greater in term parturients and post-partum patients, respectively, than in non-pregnant women. However, the clinical studies that demonstrated this increased sensitivity concentrated on sensory spread and intensity and any possible effect of pregnancy on motor fibres has received much less attention. In addition, studies assessing sensitivity to local anaesthetics after spinal injection during pregnancy remain rare. In one experimental study, spinal root axons from full-term pregnant rats were not more susceptible to the anaesthetic effect of bupivacaine when compared with non-pregnant controls.19 In the clinical study of Datta et al.,18 which showed a significant effect of pregnancy on sensory block, motor block was not evaluated. It would be useful to assess concomitantly motor and sensory block because a differential effect of pregnancy cannot be excluded. In the study of Fassoulaki et al.,20 significant differences in sensory block were observed between pregnant and non-pregnant women 10 min after intrathecal injection of hyperbaric lidocaine, but intensity of motor block was similar and there was no difference in motor block intensity at the end of surgery. Motor block was assessed using a 4-point measurement scale, which might have been insufficiently sensitive to detect a difference. The authors suggested that because almost all the women had a dense motor block, it might have been impossible to demonstrate a difference between the groups. This suggests that evaluation of possible differences in motor block in conditions in which the motor block is better controlled would be attractive. Because of the conflicting results discussed above and because additional data are needed in a clinical context in which motor block is less intense, the study by Camorcia et al.21 published in the present issue of European Journal of Anaesthesiology is welcome. Using the now well established up and down sequential allocation method, the authors determined that the ED50 of intrathecal bupivacaine in pregnant women is significantly smaller than in non-pregnant women. Although this study was not performed to elucidate the potential mechanism, it clearly adds to the list of previous studies, which show that pregnancy increases sensitivity to local anaesthetics and demonstrates that the increased sensitivity includes motor fibres. The effect of pregnancy has been relatively well studied, even though there remains some controversy. In contrast, sex-based differences in the efficacy of local anaesthetics have not been demonstrated to date. This is surprising, given the numerous articles that have demonstrated increased pain sensitivity in women. The study by Camorcia et al.21 is, therefore, of great interest because, to my knowledge, it is the first to compare the effects of intrathecal local anaesthetics in men and women. The authors report that motor fibres appear to be less sensitive to bupivacaine in men than in women. Camorcia et al. conclude that mechanical influences (e.g. the influence of weight and height on spread of local anaesthetic solution) are probably not sufficient to explain this result and it is tempting to suggest that a different hormonal profile may play a key role. Unfortunately, data from this study are limited to motor block, and additional studies are needed to obtain a fuller picture. It is still unclear whether sex-based differences should influence practical dosing of local anaesthetics because the differences appear to be small and interindividual variability is significant. This study emphasises the principle that patient-centred care is important and that everything should be done to administer the appropriate dose to each patient under our care.