The Electroencephalographic Effects of IV Anesthetic Doses of Melatonin: Comparative Studies with Thiopental and Propofol

We have demonstrated that large-dose IV melatonin can exert hypnotic effects similar to those caused by thiopental and propofol. In this study, we compared the electroencephalographic (EEG) effects of melatonin with those of thiopental and propofol. Sprague-Dawley rats were assigned to receive equipotent bolus doses of thiopental (23.8 mg/kg), propofol (14.9 mg/kg), or melatonin (312 mg/kg). EEG effects were recorded at periodic intervals over 10 minutes. Of eight processed EEG variables analyzed, only relative total power (rTP), relative spectral edge 95% (rSE95), and relative approximate entropy (rAE) were altered by all drugs compared with their control vehicles. Drug administration decreased the values relative to baseline, with subsequent return toward baseline during the 10-min time course. Thiopental significantly increased rTP, whereas propofol and melatonin did not. All drugs significantly decreased rSE95. However, the time course of peak effect and duration differed for each, with melatonin exhibiting a slower onset and a more sustained EEG effect. All drugs significantly decreased rAE, with similar time courses for thiopental and propofol and a slower onset/longer duration for melatonin. Melatonin produced effects on processed EEG variables similar to those of thiopental and propofol, specifically a decrease in the rSE95 and a decrease in the rAE.

[1]  P Lavie,et al.  Melatonin possesses time-dependent hypnotic effects. , 1994, Sleep.

[2]  R. Reiter,et al.  Utility of high doses of melatonin as adjunctive anticonvulsant therapy in a child with severe myoclonic epilepsy: Two years' experience , 1997, Journal of pineal research.

[3]  J. Theron,et al.  The effect of intravenous administration of melatonin on cardiovascular parameters of the baboon (Papio ursinus) , 1991, Journal of pineal research.

[4]  M. Naguib,et al.  The comparative dose-response effects of melatonin and midazolam for premedication of adult patients: a double-blinded, placebo-controlled study. , 2000 .

[5]  I. Rampil,et al.  Changes in EEG spectral edge frequency correlate with the hemodynamic response to laryngoscopy and intubation. , 1987, Anesthesiology.

[6]  J. E. Skinner,et al.  Chaos and physiology: deterministic chaos in excitable cell assemblies. , 1994, Physiological reviews.

[7]  N Birbaumer,et al.  Chaos and order in the human brain. , 1995, Electroencephalography and clinical neurophysiology. Supplement.

[8]  S L Shafer,et al.  A comparison of spectral edge, delta power, and bispectral index as EEG measures of alfentanil, propofol, and midazolam drug effect , 1997, Clinical pharmacology and therapeutics.

[9]  D. Sugden.  Psychopharmacological effects of melatonin in mouse and rat. , 1983, The Journal of pharmacology and experimental therapeutics.

[10]  J. Bruhn,et al.  Shannon Entropy Applied to the Measurement of the Electroencephalographic Effects of Desflurane , 2001, Anesthesiology.

[11]  R. Reiter,et al.  Melatonin As a Free Radical Scavenger: Implications for Aging and Age‐Related Diseases a , 1994, Annals of the New York Academy of Sciences.

[12]  E. Mortier,et al.  EEG and SEMG monitoring during induction and maintenance of anesthesia with propofol , 1989, International journal of clinical monitoring and computing.

[13]  J. Bruhn,et al.  Approximate Entropy as an Electroencephalographic Measure of Anesthetic Drug Effect during Desflurane Anesthesia , 2000, Anesthesiology.

[14]  P. Schmid,et al.  Pharmacological effects of intravenous melatonin: comparative studies with thiopental and propofol. , 2003, British journal of anaesthesia.

[15]  Jin Liu,et al.  Electroencephalographic Bispectral Index Correlates with Intraoperative Recall and Depth of Propofol-Induced Sedation , 1997, Anesthesia and analgesia.

[16]  Steven M. Pincus,et al.  A regularity statistic for medical data analysis , 1991, Journal of Clinical Monitoring.

[17]  J. Barchas,et al.  Acute Pharmacology of Melatonin , 1967, Nature.

[18]  M. Naguib,et al.  The Comparative Dose-Response Effects of Melatonin and Midazolam for Premedication of Adult Patients: A Double-Blinded, Placebo-Controlled Study , 2000, Anesthesia and analgesia.

[19]  S. Reppert,et al.  Melatonin receptors in human hypothalamus and pituitary: implications for circadian and reproductive responses to melatonin. , 1993, The Journal of clinical endocrinology and metabolism.

[20]  M. Todd,et al.  EEGs, EEG processing, and the bispectral index. , 1998, Anesthesiology.

[21]  K. Kuizenga,et al.  Biphasic EEG changes in relation to loss of consciousness during induction with thiopental, propofol, etomidate, midazolam or sevoflurane. , 2001, British journal of anaesthesia.

[22]  P. Taylor,et al.  Effects of alfentanil on the equine electroencephalogram during anaesthesia with halothane in oxygen. , 1997, Research in veterinary science.

[23]  Ira J. Rampil,et al.  1653 and Isoflurane Produce Similar Dose‐related Changes in the Electroencephalogram of Pigs , 1988, Anesthesiology.

[24]  Power spectral analysis of the electroencephalographic and hemodynamic correlates of propofol anesthesia in the rat: Intravenous infusion , 1993, Neuroscience Letters.

[25]  M. Naguib,et al.  Premedication with melatonin: a double-blind, placebo-controlled comparison with midazolam. , 1999, British journal of anaesthesia.