Volatile anaesthetics have historically been considered to act in a nonspecific manner on the central nervous system. More recent studies, however, have revealed that the receptors for inhibitory neurotransmitters such as gamma-aminobutyric acid (GABA) and glycine are sensitive to clinically relevant concentrations of inhaled anaesthetics. The function of GABA(A) and glycine receptors is enhanced by a number of anaesthetics and alcohols, whereas activity of the related GABA rho1 receptor is reduced. We have used this difference in pharmacology to investigate the molecular basis for modulation of these receptors by anaesthetics and alcohols. By using chimaeric receptor constructs, we have identified a region of 45 amino-acid residues that is both necessary and sufficient for the enhancement of receptor function. Within this region, two specific amino-acid residues in transmembrane domains 2 and 3 are critical for allosteric modulation of both GABA(A) and glycine receptors by alcohols and two volatile anaesthetics. These observations support the idea that anaesthetics exert a specific effect on these ion-channel proteins, and allow for the future testing of specific hypotheses of the action of anaesthetics.

The GABA(A) receptor is an important target for a variety of general anesthetics (Franks and Lieb, 1994) and for benzodiazepines such as diazepam. Specific point mutations in the GABA(A) receptor selectively abolish regulation by benzodiazepines (Rudolph et al., 1999; McKernan et al., 2000) and by anesthetic ethers (Mihic et al., 1997; Krasowski et al., 1998; Koltchine et al., 1999), suggesting the existence of discrete binding sites on the GABA(A) receptor for these drugs. Using anesthetics of different molecular size (isoflurane > halothane > chloroform) together with complementary mutagenesis of specific amino acid side chains, we estimate the volume of a proposed anesthetic binding site as between 250 and 370 A(3). The results of the "cutoff" analysis suggest a common site of action for the anesthetics isoflurane, halothane, and chloroform on the GABA(A) receptor. Moreover, the data support a crucial role for Leu232, Ser270, and Ala291 in the alpha subunit in defining the boundaries of an amphipathic cavity, which can accommodate a variety of small general anesthetic molecules.

In MO patients undergoing bariatric surgery in the "ramped position," there was no relationship between the presence and severity of OSA, BMI, or NC and difficulty of intubation or laryngoscopy grade. Only a Mallampati score of 3 or 4 or male gender predicted difficult intubation.

Administration of continuous positive airway pressure immediately after extubation maintains spirometric lung function at 24 h after laparoscopic bariatric surgery better than continuous positive airway pressure started in the postanesthesia care unit.

Cardiac arrest associated with reperfusion of the liver allograft in a euvolemic patient is a rare but potentially devastating event. There are few case series describing experience with this complication and no published management protocols guiding treatment. This article is a retrospective case series of patients experiencing post-reperfusion intraoperative cardiac arrest between 1997 and 2011. Among 1581 liver transplants, 16 (1%) patients experienced post-reperfusion cardiac arrest. Among patients with intraoperative arrests, 14 (88%) patients required open cardiac massage. Seven (44%) were placed on cardiopulmonary bypass (CPB) when cardiac activity failed to adequately recover. Placement on CPB reversed cardiac pump failure and established a perfusing rhythm in six of seven (86%) recipients, leading to one of seven (14%) intraoperative mortality. Recovery of myocardial function was associated with low early survival with only 3/7 (43%) patients who underwent CPB surviving until discharge. Among all patients who survived the perioperative period, one-yr survival was 70% (N = 7), and five-yr survival was 50% (N = 5). Cardiac arrest during liver transplantation is associated with a poor prognosis during the perioperative period. In patients who do not recover cardiac activity after standard resuscitative measures, progression to physiologic support with systemic anticoagulation and CPB may allow correction of electrolyte derangements, maintenance of cerebral perfusion, and myocardial recovery.