Academic Unit of Anaesthesia and Intensive Care, Institute of Medical Sciences, University of Aberdeen, Aberdeen AB25 2ZD, UK*Corresponding author
Accepted for publication: May 25, 2001
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Abstract |
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Methods. In this pilot study we measured cGMP in the saliva of six healthy volunteers and eight patients undergoing general anaesthesia for minor gynaecological procedures. Samples were obtained using a commercially available sampling device and cGMP was determined with an enzyme immunoassay and results expressed as a cGMP per mg protein.
Results. There was no statistically significant variation in salivary cGMP either day-to-day or between time points in healthy volunteers. Analysis of variance of salivary cGMP of patients undergoing general anaesthesia showed that cGMP increased significantly intraoperatively and returned to preoperative levels after surgery (P=0.03).
Conclusions. This is the first time that real time in vivo changes in salivary cGMP levels during general anaesthesia in humans have been demonstrated and may allow an alternative technique for measuring depth of anaesthesia in the future.
Br J Anaesth 2002; 89: 6357
Keywords: anaesthesia, depth; anaesthesia, general; metabolism, second messengers; monitoring, depth of anaesthesia
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Introduction |
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cGMP is detectable in saliva, providing an easily accessible sample for measurement during anaesthesia. There are no previous data regarding variation in salivary cGMP in healthy subjects in the absence of anaesthesia, and therefore initial studies assessing any variation were required before undertaking studies in anaesthetized subjects. The aim of this study was to assess whether changes in salivary cGMP occurred during anaesthesia in humans.
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Methods and results |
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Saliva samples were frozen in liquid nitrogen immediately after collection and stored at 80°C until analysis. For the assay, samples were thawed on ice and microwaved for 8 s to halt enzyme activity.4 5 cGMP concentrations were determined using a sensitive enzyme immunoassay kit (R&D Systems Europe, Abingdon, Oxon, UK) as described previously.5 Protein was measured using Bradford reagent (Sigma-Aldrich, Poole, Dorset, UK) and results were expressed as saliva cGMP pmol (mg protein)1. Data were analysed using Friedman analysis of variance with Wilcoxon signed ranks post hoc testing as appropriate and Bonferroni correction for multiple comparisons as necessary.
There was no statistically significant variation in salivary cGMP either day-to-day or between time points in healthy volunteers. In patients, analysis of variance revealed a statistically significant change in cGMP (P=0.03) during anaesthesia and surgery with no change in salivary protein concentration. Post hoc analysis showed that cGMP increased significantly intraoperatively (P=0.023) and returned to preoperative levels following surgery (Fig. 1).
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Comment |
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Studies in anaesthetized animals have shown decreases in cGMP within the central nervous system after halothane or isoflurane anaesthesia.5 However, in the present study, salivary cGMP increased during anaesthesia compared with concentrations immediately pre-induction. This may be partially explained by nitric oxide synthase activity or haemoxygenase activity during anaesthesia. Both nitric oxide, produced by the action of nitric oxide synthase, and carbon monoxide, the product of haemoxygenase activity, are potent activators of soluble guanyl cyclase.6
The results of this study need to be extended to a larger study of various anaesthetic techniques to establish whether this is a common link for a mechanism of anaesthesia in humans. Also, the possible development of a real time cGMP monitor is appealing and may allow an alternative technique for measuring depth of anaesthesia.
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Acknowledgements |
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References |
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2 Adachi T, Kurata J, Nakao S, et al. Nitric oxide synthase inhibitor does not reduce minimum alveolar concentration of halothane in rats. Anesth Analg 1994; 78: 11547[Abstract]
3 Ichinose F, Huang PL, Zapol W. Effects of targeted neuronal nitric oxide synthase gene disruption and nitroG-arginine methylester on the threshold for isoflurane. Anesthesiology 1995; 83: 1018[ISI][Medline]
4 Vulliemoz Y,Versoky M, Lapert M, Triner L. Effect of enflurane on cerebellar cGMP and and on motor activity in the mouse. Br J Anaesth 1983; 55: 2508
5 Galley HF, Le Cras AE, Logan SD, Webster NR. Differential nitric oxide synthase activity, co-factor availability and cGMP accumulation in the central nervous system during anaesthesia. Br J Anaesth 2001; 86: 38894
6 Morisaki H, Katayama T, Kotake Y, et al. Roles of carbon monoxide in leukocyte and platelet dynamics in rat mesenteric during sevoflurane anesthesia. Anesthesiology 2001; 95: 1929[ISI][Medline]