Sedation is an area of active research motivated by the clinical need for safe and reliable techniques. An understanding of the cellular and molecular physiology of sedation will contribute to the rational development of sedating drugs.These important goals are hampered, however, by the complexity of sedation as an altered state of arousal and by the diversity of sedating drugs.
According to SHOBHA MALVIYA, MD, NORAH N. NAUGHTON, MD, and KEVIN K. TREMPER, MD, PhD, some scientists hypothesize that brain mechanisms that evolved to generate naturally occurring states of sleep generate the traits that define levels of sedation and various states of general anesthesia. The hypothesis offers several key advantages. First, it is simpler and more direct than the alternate hypothesis, which requires a cartography of cellular changes that are unique to each disparate drug and associated co-variates such as dose, route of delivery,and pharmacokinetics. Even a decade ago, this alternate hypothesis would have required evaluation of more than 80 different drugs and drug combinations used to produce sedation. Second, the hypothesis encourages characterization of alterations in traits such as the electroencephalogram(EEG), respiration, or muscle tone, which are characteristic of sedation. Third, the hypothesis offers a standardized control condition (normal wakefulness) to which drug-induced trait and state changes can be compared. Finally, the hypothesis is empowered by the fact that natural sleep is the most thoroughly characterized arousal state at the cellular level.Thus, sleep neurobiology offers a conceptual framework for unifying the diverse collection of descriptive data that now characterize sedation.
During sedation, the effects of pharmacological agents are superimposed on a patient’s emotional state and level of arousal. A patient’s endogenous behavioral state is particularly relevant for the practitioners who use sedation to enhance patient comfort. One study of 76 children aged 18-61 months noted that parental perception of a child being tired was related to poor sedation. It has been noted that “the declaration of any given state may be incomplete and that states can oscillate rapidly, resulting in bizarre and important clinical syndromes. Narcolepsy provides one example during which physiological and behavioral traits characteristic of rapid eye movement(REM) sleep intrude upon and disrupt wakefulness. A better understanding of the endogenously generated traits outlined is likely to advance understanding of the mechanisms that actively generate states of sedation.
Source: Sedation and Analgesia for Diagnostic and Therapeutic Procedures by SHOBHA MALVIYA, MD, NORAH N. NAUGHTON, MD, and KEVIN K. TREMPER, MD, PhD.