title: Inhaled anaesthetics and nitrous oxide: Complexities overlooked: things may not be what they seem.
abstract: This review re-examines existing pharmacokinetic and pharmacodynamic concepts of inhaled anaesthetics. After showing where uptake is hidden in the classic FA/FI curve, it is argued that target-controlled delivery of inhaled agents warrants a different interpretation of the factors affecting this curve (cardiac output, ventilation and blood/gas partition coefficient). Blood/gas partition coefficients of modern agents may be less important clinically than generally assumed. The partial pressure cascade from delivered to inspired to end-expired is re-examined to better understand the effect of rebreathing during low-flow anaesthesia, including the possibility of developing a hypoxic inspired mixture despite existing machine standards. Inhaled agents are easy to administer because they are transferred according to partial pressure gradients. In addition, the narrow dose-response curves for the three end points of general anaesthesia (loss of response to verbal command, immobility and autonomic reflex control) allow the clinical use of MACawake, MAC and MACBAR to determine depth of anaesthesia. Opioids differentially affect these clinical effects of inhaled agents. The effect of ventilation-perfusion relationships on gas uptake is discussed, and it is shown how moving beyond Riley's useful but simplistic model allows us to better understand both the concept and the magnitude of the second gas effect of nitrous oxide. It is argued that nitrous oxide remains a clinically useful drug. We hope to bring old (but ignored) and new (but potentially overlooked) information into the educational and clinical arenas to stimulate discussion among clinicians and researchers. We should not let technology pass by our all too engrained older concepts.
authors.affiliation: From the Department of Anesthesiology, Intensive Care and Pain Therapy, OLV Hospital, Aalst, Belgium (JH); Department of Anaesthesiology, Austin Hospital and University of Melbourne, Melbourne, Australia (PP); Department of Anesthesiology, Intensive Care and Pain Therapy, OLV Hospital, Aalst, Belgium (RC); and Department of Anesthesiology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA (ADW) *Jan Hendrickx, Philip Peyton and Andre De Wolf are members of the NAVAt group.
authors.forename: Jan
authors.initials: J
authors.lastname: Hendrickx
authors.forename: Philip
authors.initials: P
authors.lastname: Peyton
authors.forename: Rik
authors.initials: R
authors.lastname: Carette
authors.forename: Andre
authors.initials: A
authors.lastname: De Wolf
mesh_terms: D000701:Analgesics, Opioid / Q000008:administration & dosage; D000764:Anesthesia, Closed-Circuit / Q000379:methods / Q000639:trends; D000769:Anesthesia, Inhalation / Q000379:methods* / Q000639:trends; D018685:Anesthetics, Inhalation / Q000008:administration & dosage*; D001784:Blood Gas Analysis / Q000379:methods; D006801:Humans; D009609:Nitrous Oxide / Q000008:administration & dosage*; D010313:Partial Pressure
chemical_list: D000701:Analgesics, Opioid; D018685:Anesthetics, Inhalation; D009609:Nitrous Oxide