Additional file 1 of Facilitators and barriers to the implementation of prehabilitation for frail patients into routine health care: a realist review

Additional file 1

Influence of Volatile Anesthesia on the Release of Glutamate and other Amino Acids in the Nucleus Accumbens in a Rat Model of Alcohol Withdrawal: A Pilot Study

<div><p>Background</p><p>Alcohol withdrawal syndrome is a potentially life-threatening condition, which can occur when patients with alcohol use disorders undergo general anesthesia. Excitatory amino acids, such as glutamate, act as neurotransmitters and are known to play a key role in alcohol withdrawal syndrome. To understand this process better, we investigated the influence of isoflurane, sevoflurane, and desflurane anesthesia on the profile of excitatory and inhibitory amino acids in the nucleus accumbens (NAcc) of alcohol-withdrawn rats (AWR).</p><p>Methods</p><p>Eighty Wistar rats were randomized into two groups of 40, pair-fed with alcoholic or non-alcoholic nutrition. Nutrition was withdrawn and microdialysis was performed to measure the activity of amino acids in the NAcc. The onset time of the withdrawal syndrome was first determined in an experiment with 20 rats. Sixty rats then received isoflurane, sevoflurane, or desflurane anesthesia for three hours during the withdrawal period, followed by one hour of elimination. Amino acid concentrations were measured using chromatography and results were compared to baseline levels measured prior to induction of anesthesia.</p><p>Results</p><p>Glutamate release increased in the alcohol group at five hours after the last alcohol intake (p = 0.002). After 140 min, desflurane anesthesia led to a lower release of glutamate (p < 0.001) and aspartate (p = 0.0007) in AWR compared to controls. GABA release under and after desflurane anesthesia was also significantly lower in AWR than controls (p = 0.023). Over the course of isoflurane anesthesia, arginine release decreased in AWR compared to controls (p < 0.001), and aspartate release increased after induction relative to controls (p_20min = 0.015 and p_40min = 0.006). However, amino acid levels did not differ between the groups as a result of sevoflurane anesthesia.</p><p>Conclusions</p><p>Each of three volatile anesthetics we studied showed different effects on excitatory and inhibitory amino acid concentrations. Under desflurane anesthesia, both glutamate and aspartate showed a tendency to be lower in AWR than controls over the whole timecourse. The inhibitory amino acid arginine increased in AWR compared to controls, whereas GABA levels decreased. However, there were no significant differences in amino acid concentrations under or after sevoflurane anesthesia. Under isoflurane, aspartate release increased in AWR following induction, and from 40 min to 140 min arginine release in controls was elevated. The precise mechanisms through which each of the volatile anesthetics affected amino acid concentrations are still unclear and further experimental research is required to draw reliable conclusions.</p></div

P-values for differences in GABA concentration from MANOVA analyses.

<p>P-values for differences in GABA concentration from MANOVA analyses.</p

Experimental schedule for determining the withdrawal onset time.

<p>Experimental schedule for determining the withdrawal onset time.</p

Aspartate levels under the different volatile anesthetics.

<p>Aspartate release in the alcohol vs. control groups during withdrawal under volatile anesthesia (0–180 min), emergence (↓) and post-anesthesia recovery (200–240 min). Data are shown as median % of baseline with interquartile ranges (25–75%) and plotted over time. (A) isoflurane: alcohol vs. control, n = 9 vs. 10. (B) sevoflurane: alcohol vs. control, n = 9 vs. 10. (C) desflurane: alcohol vs. control, n = 9 vs. 9. Post-hoc univariate group comparisons were performed using Mann-Whitney U tests (*p < 0.05 and **p < 0.01).</p

Elevated glutamate levels in the alcohol group compared to controls indicate that the alcohol withdrawal response occurred five hours after the last intake of alcohol.

<p>Glutamate release as median % of baseline with interquartile ranges (25–75%) plotted over time (control: n = 8; alcohol: n = 6). Group statistical analyses were performed using Mann-Whitney U tests (**p < 0.01).</p

The GABA concentration was lower in AWR than controls under desflurane anesthesia.

<p>GABA release in the alcohol vs. control groups during withdrawal under volatile anesthesia (0–180 min), emergence (↓) and post-anesthesia recovery (200–240 min). Data are shown as median % of baseline with interquartile ranges (25–75%) and plotted over time (A) isoflurane: alcohol vs. control, n = 9 vs. 10. (B) sevoflurane: alcohol vs. control, n = 9 vs. 10. (C) desflurane: alcohol vs. control, n = 9 vs. 9. Post-hoc univariate group comparisons were performed using Mann-Whitney U tests (*p < 0.05 and **p < 0.01).</p

P-values for differences in aspartate concentration from MANOVA analyses.

<p>P-values for differences in aspartate concentration from MANOVA analyses.</p

P-values for differences in glutamate concentration from MANOVA analyses.

<p>P-values for differences in glutamate concentration from MANOVA analyses.</p

Schedule for the feeding period.

<p>Schedule for the feeding period.</p