Handbook of experimental pharmacology
-
Handb Exp Pharmacol · Jan 2008
ReviewAdvanced technologies and devices for inhalational anesthetic drug dosing.
Technological advances in micromechanics, optical sensing, and computing have led to innovative and reliable concepts of precise dosing and sensing of modern volatile anesthetics. Mixing of saturated desflurane flow with fresh gas flow (FGF) requires differential pressure sensing between the two circuits for precise delivery. The medical gas xenon is administered most economically in a closed circuit breathing system. ⋯ Delivery of xenon is presented, followed by a discussion of direct injection of volatile anesthetics and of a device designed to conserve anesthetic drugs. Next, innovative sensing technologies are presented for reliable control and precise metering of the delivered volatile anesthetics. Finally, we discuss the technical challenges of automatic control in low-flow and closed circuit breathing systems in anesthesia.
-
Anesthesia cannot be defined in an unambiguous manner. The essential components of general anesthesia are absence of consciousness and pain. This translates into two particular qualities: (1) sedation and hypnosis, i.e., mental blockade and (2) analgesia/antinociception, i.e., sensory blockade. ⋯ Clinical assessment of analgesia requires a conscious patient, so antinociception is difficult to measure. Several methods of objective quantification on the basis of electrical brain activity are discussed including EEG and evoked potentials. Despite numerous indexes of the hypnotic component of anesthesia, there is no parameter that unambiguously quantifies the level of mental or sensory blockade.
-
We do not know how general anesthetics cause their desired effects. Contrary to what has been thought until relatively recently, the clinical state of anesthesia consists of multiple components that are mediated via interaction of the anesthetic drugs with different targets on the molecular-cellular, the network, and the structural-anatomical levels. The molecular targets by which some of these drugs induce the different components of "anesthesia" may be rather specific: discrete mutations of single amino acids in specific proteins profoundly affect the ability of certain anesthetics to achieve specific endpoints. ⋯ The CNS appears to be susceptible to anesthetic neurotoxicity primarily at the extremes of ages, possibly via different pathways: in the neonate, during the period of most intense synaptogenesis, anesthetics can induce excessive apoptosis; in the aging CNS subtle cognitive dysfunction can persist long after clearance of the drug, and processes reminiscent of neurodegenerative disorders may be accelerated (Eckenhoff et al. 2004). At all ages, anesthetics affect gene expression-regulating protein synthesis in poorly understood ways. While it seems reasonable to assume that the vast majority of our patients completely restore homeostasis after general anesthesia, it is also time to acknowledge that exposure to these drugs has more profound and longer lasting effects on the brain than heretofore imagined.
-
Handb Exp Pharmacol · Jan 2008
Review Historical ArticleInhalation anaesthesia: from diethyl ether to xenon.
Modern anaesthesia is said to have began with the successful demonstration of ether anaesthesia by William Morton in October 1846, even though anaesthesia with nitrous oxide had been used in dentistry 2 years before. Anaesthesia with ether, nitrous oxide and chloroform (introduced in 1847) rapidly became commonplace for surgery. Of these, only nitrous oxide remains in use today. ⋯ Recently there has been a renewed interest in xenon, one of the noble gases. Xenon has many of the properties of an ideal anaesthetic. The major factor limiting its more widespread is the high cost, about 2,000 times the cost of nitrous oxide.
-
It belongs to the particularities of anaesthesia that the conscious response of the patient to drug therapy is not available for the adjustment of drug therapy and that the side-effects of anaesthetic drug therapy would be in general lethal if no special measures were taken such as artificial ventilation. Both conditions do not allow for a slow, time-consuming titration of drug effect towards the therapeutically effective window, but measures have to be taken to reach a therapeutic target fast (within seconds to a few minutes), reliably, and with precision. ⋯ Whereas TCI presents an open-loop dosing strategy (the past output does not influence the future input), current research deals with the model-based adaptive closed-loop administration of anaesthetics. In these systems the past output is used to adapt and individualize the initial pk-pd model to the patients and thus has an influence on future drug dosing which is based on the adapted model.