The thermodynamics of general anesthesia

It is known that the action of general anesthetics is proportional to their partition coefficient in lipid membranes (Meyer-Overton rule). This solubility is, however, directly related to the depression of the temperature of the melting transition found close to body temperature in biomembranes. We propose a thermodynamic extension of the Meyer-Overton rule which is based on free energy changes in the system and thus automatically incorporates the effects of melting point depression. This model provides a quantitative explanation of the pressure reversal of anesthesia. Further, it explains why inflammation and the addition of divalent cations reduce the effectiveness of anesthesia.Comment: 7 pages, 2 figure

Propofol Induction Reduces the Capacity for Neural Information Integration: Implications for the Mechanism of Consciousness and General Anesthesia

The cognitive unbinding paradigm suggests that the synthesis of cognitive information is attenuated by general anesthesia. Here, we investigated the functional organization of brain activities in the conscious and anesthetized states, based on characteristic functional segregation and integration of electroencephalography (EEG). EEG recordings were obtained from 14 subjects undergoing induction of general anesthesia with propofol. We quantified changes in mean information integration capacity in each band of the EEG. After induction with propofol, mean information integration capacity was reduced most prominently in the gamma band of the EEG (p=0.0001). Furthermore, we demonstrate that loss of consciousness is reflected by the breakdown of the spatiotemporal organization of gamma waves. Induction of general anesthesia with propofol reduces the capacity for information integration in the brain. These data directly support the information integration theory of consciousness and the cognitive unbinding paradigm of general anesthesia

Anesthesia in the surgery of strabismus: role of anesthetic agents in the ocular deviation and surgical outcome

Purpose: To determine whether the changes in the ocular alignment following general anesthesia, maintained with two different inhalational anesthetic agents, sevoflurane and desflurane, can be used as a predictor for surgical outcomes in children with esotropia. Methods: The authors obtained digital photographs of 42 children with esotropia; 21 patients underwent strabismus surgery with general inhalation anesthesia with sevoflurane (group A), 21 patients with inhalatory anesthesia with desflurane (Group B), as maintenance general anesthesia agents. For each patient, the corneal reflexes position were digitally measured and compared with the preoperative ocular deviation’s angle; the correlation with surgical outcome, one year after, was considered. Results: The patients in both groups showed a decrease of the squint angle, or eye’s gap position after the induction of general anesthesia. In group B, this divergence was significantly higher than in group A (P<0.001). In both groups, there was a linear correlation between the preoperative angle and shortly after the induction of general anesthesia. Patients ranging a corneal reflexes position within 1 SD (15Δ) evidenced higher success of surgery (p<0.05) of patients>1 SD. Conclusion: Changes in the ocular deviation with sevoflurane and desflurane, can be predictive for surgery outcome in children with esotropia. Furthermore, desflurane evidenced greater effects on the ocular deviation compared to sevoflurane, thus confirming to be the inhalational anesthetic of choice in strabismus surgery

Comparison of Anesthesia for Dental/Oral Surgery by Office-based Dentist Anesthesiologists versus Operating Room-based Physician Anesthesiologists

Few studies have examined the practice characteristics of dentist anesthesiologists and compared them to other anesthesia providers. Using outcomes from the National Anesthesia Clinical Outcomes Registry and the Society for Ambulatory Anesthesia Clinical Outcomes Registry for dental/oral surgery procedures, we compared 7133 predominantly office-based anesthetics by dentist anesthesiologists to 106,420 predominantly operating room anesthetics performed by physician anesthesia providers. These encounters were contrasted with 34,191 previously published encounters from the practices of oral and maxillofacial surgeons. Children younger than 6 years received the greatest proportion of general anesthetic services rendered by both dentist anesthesiologists and hospital-based anesthesia providers. These general anesthesia services were primarily provided for complete dental rehabilitation for early childhood caries. Overall treatment time for complete dental rehabilitation in the office-based setting by dentist anesthesiologists was significantly shorter than comparable care provided in the hospital operating room and surgery centers. The anesthesia care provided by dentist anesthesiologists was found to be separate and distinct from anesthesia care provided by oral and maxillofacial surgeons, which was primarily administered to adults for very brief surgical procedures. Cases performed by dentist anesthesiologists and hospital-based anesthesia providers were for much younger patients and of significantly longer duration when compared with anesthesia administered by oral and maxillofacial surgeons. Despite the limited descriptive power of the current registries, office-based anesthesia rendered by dentist anesthesiologists is clearly a unique and efficient mode of anesthesia care for dentistry

Cognitive dysfunction following desflurane versus sevoflurane general anesthesia in elderly patients: a randomized controlled trial.

UnlabelledAs life expectancy increases, more patients ≥65 years undergo general anesthesia. Anesthetic agents may contribute to postoperative cognitive dysfunction, and incidence may differ with anesthetic agents or intraoperative anesthesia depth. Responses to anesthetic adjuvants vary among elderly patients. Processed electroencephalography guidance of anesthetic may better ensure equivalent cerebral suppression. This study investigates postoperative cognitive dysfunction differences in elderly patients given desflurane or sevoflurane using processed electroencephalography guidance.IRB approved, randomized trial enrolled consenting patients ≥65 years scheduled for elective surgery requiring general anesthesia ≥120 minute duration. After written informed consent, patients were randomly assigned to sevoflurane or desflurane. No perioperative benzodiazepines were administered. Cognitive impairment was measured by an investigator blinded to group assignment using mini-Mental Status Examination (MMSE) at baseline; 1, 6, and 24 hours after the end of anesthesia. Mean arterial pressure was maintained within 20% of baseline. Anesthetic dose was adjusted to maintain moderate general anesthesia per processed electroencephalograpy (Patient State Index 25 to 50). The primary outcome measure was intergroup difference in MMSE change 1 hour after anesthesia (median; 95% confidence interval).110 patients consented; 26 were not included for analysis (no general anesthesia; withdrew consent; baseline MMSE abnormality; inability to perform postoperative MMSE; data capture failure); 47 sevoflurane and 37 desflurane were analyzed. There were no significant differences in patient characteristics; intraoperative mean blood pressure (desflurane 86.4; 81.3 to 89.6 versus sevoflurane 82.5; 80.2 to 86.1 mmHg; p = 0.42) or Patient State Index (desflurane 41.9; 39.0 to 44.0 versus sevoflurane 41.0; 37.5 to 44.0; p = 0.60) despite a lower MAC fraction in desflurane (0.82; 0.77 to 0.86) versus sevoflurane (0.96; 0.91 to 1.03; p < 0.001). MMSE decreased 1 hour after anesthesia (p < 0.001). The decrease at one hour was larger in sevoflurane (-2.5; -3.3 to -1.8) than desflurane (-1.3; -2.2 to -0.5; p = 0.03). MMSE returned to baseline by 6 hours after anesthesia.ConclusionsFor elderly patients in whom depth of anesthesia is maintained in the moderate range, both desflurane and sevoflurane are associated with transient decreases in cognitive function as measured by MMSE after anesthesia, with clinically insignificant differences between them in this setting.Trial registryClinicalTrials.gov NCT01199913

General anesthesia reduces complexity and temporal asymmetry of the informational structures derived from neural recordings in Drosophila

We apply techniques from the field of computational mechanics to evaluate the statistical complexity of neural recording data from fruit flies. First, we connect statistical complexity to the flies' level of conscious arousal, which is manipulated by general anesthesia (isoflurane). We show that the complexity of even single channel time series data decreases under anesthesia. The observed difference in complexity between the two states of conscious arousal increases as higher orders of temporal correlations are taken into account. We then go on to show that, in addition to reducing complexity, anesthesia also modulates the informational structure between the forward- and reverse-time neural signals. Specifically, using three distinct notions of temporal asymmetry we show that anesthesia reduces temporal asymmetry on information-theoretic and information-geometric grounds. In contrast to prior work, our results show that: (1) Complexity differences can emerge at very short timescales and across broad regions of the fly brain, thus heralding the macroscopic state of anesthesia in a previously unforeseen manner, and (2) that general anesthesia also modulates the temporal asymmetry of neural signals. Together, our results demonstrate that anesthetized brains become both less structured and more reversible.Comment: 14 pages, 6 figures. Comments welcome; Added time-reversal analysis, updated discussion, new figures (Fig. 5 & Fig. 6) and Tables (Tab. 1

General anesthesia does not have persistent effects on attention in rodents

Background: Studies in animals have shown that general anesthesia can cause persistent spatial memory impairment, but the influence of anesthetics on other cognitive functions is unclear. This study tested whether exposure to general anesthesia without surgery caused a persistent deficit in attention in rodents.Methods: To evaluate whether anesthesia has persistent effects on attention, rats were randomized to three groups. Group A was exposed for 2 h to isoflurane anesthesia, and tested the following seven days for attentional deficits. Group B was used as a control and received room air before attentional testing. Since there is some evidence that a subanesthetic dose of ketamine can improve cognition and reduce disorders of attention after surgery, rats in group C were exposed to isoflurane anesthesia in combination with a ketamine injection before cognitive assessment. Attention was measured in rats using the 5-Choice Serial Reaction Time Task, for which animals were trained to respond with a nose poke on a touchscreen to a brief, unpredictable visual stimulus in one of five possible grid locations to receive a food reward. Attention was analyzed as % accuracy, % omission, and premature responses.Results: Evaluating acute attention by comparing baseline values with data from the day after intervention did not reveal any differences in attentional measurements. No significant differences were seen in % accuracy, % omission, and premature responses for the three groups tested for 7 consecutive days.Conclusion: These data in healthy rodents suggest that general anesthesia without surgery has no persistent effect on attention and the addition of ketamine does not alter the outcome

The thermodynamics of general and local anesthesia

General anesthetics are known to cause depression of the freezing point of transitions in biomembranes. This is a consequence of ideal mixing of the anesthetic drugs in the membrane fluid phase and exclusion from the solid phase. Such a generic law provides physical justification of the famous Meyer-Overton rule. We show here that general anesthetics, barbiturates and local anesthetics all display the same effect on melting transitions. Their effect is reversed by hydrostatic pressure. Thus, the thermodynamic behavior of local anesthetics is very similar to that of general anesthetics. We present a detailed thermodynamic analysis of heat capacity profiles of membranes in the presence of anesthetics. This analysis is able to describe experimentally observed calorimetric profiles and permits prediction of the anesthetic features of arbitrary molecules. In addition, we discuss the thermodynamic origin of the cutoff-effect of long-chain alcohols and the additivity of the effect of general and local anesthetics.Comment: 12 pages, 9 figures, 1 tabl

Conditions that Stabilize Membrane Domains Also Antagonize n-Alcohol Anesthesia

Diverse molecules induce general anesthesia with potency strongly correlated with both their hydrophobicity and their effects on certain ion channels. We recently observed that several n -alcohol anesthetics inhibit heterogeneity in plasma-membrane-derived vesicles by lowering the critical temperature (Tc) for phase separation. Here, we exploit conditions that stabilize membrane heterogeneity to further test the correlation between the anesthetic potency of n -alcohols and effects on Tc. First, we show that hexadecanol acts oppositely to n -alcohol anesthetics on membrane mixing and antagonizes ethanol-induced anesthesia in a tadpole behavioral assay. Second, we show that two previously described “intoxication reversers” raise Tc and counter ethanol’s effects in vesicles, mimicking the findings of previous electrophysiological and behavioral measurements. Third, we find that elevated hydrostatic pressure, long known to reverse anesthesia, also raises Tc in vesicles with a magnitude that counters the effect of butanol at relevant concentrations and pressures. Taken together, these results demonstrate that ΔTc predicts anesthetic potency for n-alcohols better than hydrophobicity in a range of contexts, supporting a mechanistic role for membrane heterogeneity in general anesthesia

Cardiovascular changes after administration of aerosolized salbutamol in horses: five cases

Prevention and treatment of intraoperative hypoxemia in horses is difficult and both efficacy and safety of therapeutic maneuvers have to be taken into account. Inhaled salbutamol has been suggested as treatment of hypoxia in horses during general anesthesia, due to safety and ease of the technique. The present report describes the occurrence of clinically relevant unwanted cardiovascular effects (i.e. tachycardia and blood pressure modifications) in 5 horses undergoing general anesthesia in dorsal recumbency after salbutamol inhalation. Balanced anesthesia based on inhalation of isoflurane in oxygen or oxygen and air and continuous rate infusion (CRI) of lidocaine, romifidine, or combination of lidocaine and guaifenesine and ketamine was provided. Supportive measures were necessary to restore normal cardiovascular function in all horses but no long-term adverse effects were noticed in any of the cases