Intraoperative Lung-Protective Ventilation Trends and Practice Patterns: A Report from the Multicenter Perioperative Outcomes Group.

BACKGROUND: The use of an intraoperative lung-protective ventilation strategy through tidal volume (TV) size reduction and positive end-expiratory pressure (PEEP) has been increasingly investigated. In this article, we describe the current intraoperative lung-protective ventilation practice patterns and trends. METHODS: By using the Multicenter Perioperative Outcomes Group database, we identified all general endotracheal anesthetics from January 2008 through December 2013 at 10 institutions. The following data were calculated: (1) percentage of patients receiving TV > 10 mL/kg predicted body weight (PBW); (2) median initial and overall TV in mL/kg PBW and; (3) percentage of patients receiving PEEP ≥ 5 cm H2O. The data were analyzed at 3-month intervals. Interinstitutional variability was assessed. RESULTS: A total of 330,823 patients met our inclusion criteria for this study. During the study period, the percentage of patients receiving TV > 10 mL/kg PBW was reduced for all patients (26% to 14%) and in the subpopulations of obese (41% to 25%), short stature (52% to 36%), and females (39% to 24%; all P values <0.001). There was a significant reduction in TV size (8.90-8.20 mL/kg PBW, P < 0.001). There was also a statistically significant but clinically irrelevant difference between initial and overall TV size (8.65 vs 8.63 mL/kg PBW, P < 0.001). Use of PEEP ≥ 5 cm H2O increased during the study period (25%-45%, P < 0.001). TV usage showed significant interinstitutional variability (P < 0.001). CONCLUSIONS: Although decreasing, a significant percentage of patients are ventilated with TV > 10 mL/kg PBW, especially if they are female, obese, or of short stature. The use of PEEP ≥ 5 cm H2O has increased significantly. Creating awareness of contemporary practice patterns and demonstrating the efficacy of lung-protective ventilation are still needed to optimize intraoperative ventilation.

Electrolytic lesions of the nucleus accumbens core (but not the medial shell) and the basolateral amygdala enhance context-specific locomotor sensitization to nicotine in rats.

We previously demonstrated that lesions of the nucleus accumbens (NAc) core enhanced locomotion and locomotor sensitization to repeated injections of nicotine in rats (Kelsey & Willmore, 2006). In this study, we compared the effects of separate lesions of the NAc core, NAc medial shell, and basolateral amygdala on context-specific locomotor sensitization to repeated injections of 0.4 mg/kg nicotine. Electrolytic lesions of the NAc core increased locomotion, and lesions of the core (but not the shell) and the basolateral amygdala enhanced context-specific locomotor sensitization by enhancing the development of sensitization in paired rats and decreasing expression in unpaired rats relative to sham-operated rats when challenged with an injection of 0.4 mg/kg nicotine in the locomotor chambers. These data are consistent with findings that the NAc core and the basolateral amygdala share a variety of behavioral functions and anatomical connections. The findings that lesions of these structures enhance context-specific locomotor sensitization while typically impairing other reward-related behaviors also indicate that the processes underlying locomotor sensitization and reward are not identical.

Role of the bed nucleus of the stria terminalis (BST) in the expression of conditioned fear.

Male Sprague-Dawley rats were trained and tested in the fear-potentiated startle (FPS) paradigm to examine the involvement of the bed nucleus of the stria terminalis (BST) in the expression of conditioned fear. Studies were designed to (a) detect physiological changes in the BST that might correlate with different levels of FPS expression and (b) determine if chemical inactivation of the BST with muscimol (1 ng) had any effect on FPS expression. The data suggest that the BST plays a role in the expression of conditioned fear and that GABA-mediated inhibition at this level may influence the level of this expression.

Behavioral and anatomical interactions between dopamine and corticotropin-releasing factor in the rat.

The neuropeptide corticotropin-releasing factor (CRF) is believed to play a role in a number of psychiatric conditions, including anxiety disorders and depression. In the present study, male Sprague Dawley rats were used to examine the behavioral effects of altering dopamine transmission on CRF-enhanced startle, a behavioral assay believed to reflect stress- or anxiety-like states. Systemic administration of the selective dopamine D1 receptor antagonist SCH 23390 [R(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrochloride] (0, 0.01, 0.05, 0.1, 0.5 mg/kg) dose dependently blocked the effect of CRF (1 microg, i.c.v.) on startle at doses that had no effect on baseline startle response. Immunohistochemical studies showed that most CRF-containing cells in the dorsolateral division of the bed nucleus of the stria terminalis (BSTld), part of the critical brain area mediating CRF-enhanced startle, are surrounded by a dense plexus of tyrosine hydroxylase (TH)-positive fibers. Intra-BSTld injections of the retrograde tracer Fluorogold (FG) into the TH field identified neurons in the major dopaminergic areas (A8-A10), but not the major noradrenergic areas [A5, A6 (locus ceruleus), A7], as a significant source of TH-positive innervation. The majority of FG-filled cells double-labeled for TH were found in the dorsocaudal A10 cell group (A10dc) located in the periaqueductal gray area. Together, these data suggest that neuronal regulation of the BSTld by specific dopaminergic pathways and receptors may be an important mechanism for controlling CRF-dependent moods and affective states. These data also suggest that compounds with D1 receptor antagonist properties might have anxiolytic-like effects that could be useful for treating conditions associated with hyperactive CRF systems.

LTP in the lateral amygdala during cocaine withdrawal.

The amygdala plays key roles in several aspects of addiction to drugs of abuse. This brain structure has been implicated in behaviours that reflect drug reward, drug seeking, and the aversive effects of drug withdrawal. Using a model that involves repeated cocaine injections to approximate 'binge' intoxication, we show in rats that during cocaine withdrawal, the impact of rewarding brain stimulation is attenuated, as quantified by alterations in intracranial self-stimulation (ICSS) behaviour. These behavioural signs of withdrawal are accompanied by enhancements of glutamatergic synaptic transmission within the lateral amygdala (LA) that occlude electrically induced long-term potentiation (LTP) in tissue slices. Synaptic enhancements during periods of cocaine withdrawal are mechanistically similar to LTP induced with electrical stimulation in control slices, as both forms of synaptic plasticity involve an increase in glutamate release. These results suggest that mechanisms of LTP within the amygdala are recruited during withdrawal from repeated exposure to cocaine. As such, they raise the possibility that the development and maintenance of addictive behaviours may involve, at least in part, mechanisms of synaptic plasticity within specific amygdala circuits.