Effects Of Volatile Anesthetic Agents Research Articles

Maybe the Wand Does Matter?

(Abstracted from Anesth Analg, 124(1):7–8, 2017) This editorial reviews both the work of Kellner et al1 and other studies that have examined the potentially relevant effects of volatile anesthetic agents on inflammation in the injured lung. The authors point out that in general most anesthesiologists likely believe the choice of anesthetic agent matters less than the anesthesiologist's skill at using it.

Effects of Volatile Anesthetic Agents on Cerebral Cortical Synchronization in Sheep

The exact neurophysiological mechanisms of anesthetic-induced unconsciousness are not yet fully elucidated. The cortical information integration theory hypothesizes that loss of consciousness during general anesthesia is associated with breakdown of long-distance cortical connectivity across multiple brain regions. However, what is the effect of anesthetics on neural activities at a smaller spatial scale? The authors analyzed a set of previously published eight-channel electrocorticogram data, obtained from a 14-mm-long linear array of electrodes in eight adult merino sheep during general anesthesia induced by sevoflurane, desflurane, isoflurane, and enflurane. The S-estimator was applied to the bi-channel coherence matrix to construct an overall index called the SI, which is the entropy of the eigenvalues of the cortical coherence for each pair of channels within the multichannel electrocorticographic dataset. The SI values increased ~30-50% from the waking to the burst-suppression states, and returned to baseline during recovery. The anesthetic-induced increase in synchrony was most marked in the α (8-13 Hz) and β (13-30 Hz) frequency bands (P<0.05). Using prediction probability (PK) analysis, we found a significant correlation between the increase in spatial synchrony (as estimated by the SI at various frequency bands) and anesthetic-induced cortical depression (as estimated by the approximate entropy). The results suggest that it is feasible to use the SI to measure cortical synchrony, and over a local spatial scale of 2-14 mm, synchrony increased during general anesthesia.

The effect of halothane and pentobarbital sodium on brain ependymal cilia

BackgroundThe effect of anesthetic agents on ependymal ciliary function is unknown. The aim of this study was to determine the effect of halothane and pentobarbital sodium on brain ependymal ciliary function.MethodsWe used an ex vivo rat brain slice model to measure ependymal ciliary beat frequency by high speed video photography at 37°C.ResultsExposure to halothane caused a significant reduction in ciliary beat frequency of 2 % (P = 0.006), 15.5 % (P < 0.001), and 21.5 % (P < 0.001) for halothane concentrations of 1.8 %, 3.4 % and 4.4 %, respectively, compared to controls. Following a one-hour wash-out period, there was no significant difference between control samples and cilia that had been exposed to 1.8 % (P = 0.5) and 3.4 % (P = 0.3) halothane. The beat frequency of cilia exposed to 4.4 % halothane had increased following the wash-out period but cilia were still beating significantly more slowly than cilia from the control group (P = <0.001).Pentobarbitone at concentrations of 25 and 50 μg/ml had no effect on ciliary beat frequency compared to controls (P = 0.6 and 0.4 respectively). A significant (P = 0.002) decrease in ciliary beat frequency was seen following incubation with a pentobarbitone concentration of 250 μg/ml (mean (SD) frequency, 24(8) Hz compared to controls, 38(9) Hz).ConclusionsHalothane reversibly inhibits the rate at which ependymal cilia beat. Pentobarbitone has no effect on ciliary activity at levels used for anesthesia. It is unclear whether the slowing of ependymal ciliary by halothane is responsible for some of the secondary central nervous system effects of volatile anesthetic agents.

Neuroprotective effect of volatile anesthetic agents: molecular mechanisms

Introduction: Intra-operative cerebral ischemia can be catastrophic, and volatile anesthetic agents have been recognized for their potential neuroprotective properties since the 1960s. In this review, we examine the neuroprotective effects of five volatile anesthetic agents in current or recent clinical use: isoflurane, sevoflurane, desflurane, halothane and enflurane.Methods: A review of publications in the National Library of Medicine and National Institutes of Health database from 1970 to 2007 was conducted.Results: Volatile anesthetic agents have been shown to be neuroprotective in multiple animal works of ischemic brain injury. Short-term neuroprotection (<1 week post-ischemia) in experimental cerebral ischemia has been reported in multiple works, although long-term neuroprotection (≥1 week post-ischemia) remains controversial. Comparison works have not demonstrated superiority of one specific volatile agent over another in experimental models of brain injury. Relatively few human works have examined the protective effects of volatile anesthetic agents and conclusive evidence of a neuroprotective effect has yet to emerge from human works.Conclusion: Proposed mechanisms related to the neuroprotective effect of volatile anesthetic agents include activation of ATP-dependent potassium channels, up-regulation of nitric oxide synthase, reduction of excitotoxic stressors and cerebral metabolic rate, augmentation of peri-ischemic cerebral blood flow and up-regulation of antiapoptotic factors including MAP kinases.

Cardioprotection with Volatile Anesthetics in Cardiac Surgery

Myocardial ischemia during the perioperative period is a major cause of morbidity and mortality after surgery. Experimental data indicate that clinical concentrations of volatile anesthetics protect the myocardium from ischemia and reperfusion injury, as shown by decreased infarct size and more rapid postoperative recovery of contractile function. These anesthetics may also mediate protective effects in other organs, such as the brain and kidney. A number of recent reports have indicated that these experimentally observed protective effects might also be present in the clinical setting. Implementation of such cardioprotection during surgery may provide an additional tool in the treatment and prevention of ischemic cardiac dysfunction in the perioperative period. This review discusses the clinical studies that have focused on the potential cardioprotective effects of volatile anesthetic agents.

Volatile anesthetics and the hypoxic ventilatory response: effects, clinical implications, and future research

This review discusses the implications of some early findings concerning the effect of volatile anesthetic agents on the human ventilatory response to hypoxia. The impact of different methods of study are discussed, as is the relevance and limitations of animal studies. The review speculates that a relatively simple observation from human study can lead to important questions, answerable using newer technologies such as functional magnetic resonance imaging, intracellular calcium imaging and single-cell/single-channel voltage clamping.

Sevoflurane or Desflurane Anesthesia plus Postoperative Propofol Sedation Attenuates Myocardial Injury after Coronary Surgery in Elderly High-risk Patients: In Reply

We read with interest the letter of Drs. Xia and Luo regarding our recent article on the cardioprotective effects of volatile anesthetic agents in elderly high-risk coronary artery patients. 1The authors propose an interesting hypothesis, which is that the use of propofol as sedation in the postoperative period on the intensive care unit may have added to the cardioprotective effects observed with sevoflurane and desflurane. Postischemic reperfusion is associated with an acute inflammatory response, involving a number of mediators, which ultimately may trigger cardiomyocyte death within the first hours after reperfusion. Drs. Xia and Luo propose that the potential of propofol in reducing cytokines and reactive oxygen species induced myocardial injury during reperfusion is responsible for the additional cardioprotective effect. It should be noted, however, that in our study, propofol administration was only started after arrival in the intensive care unit. This implies that in the sevoflurane and desflurane groups, during the first period of reperfusion (from the opening of the proximal anastomoses until the end of the operation), anesthesia was still obtained with the volatile anesthetic. If the beneficial effects of propofol during the first 2 h of reperfusion are assumed to be of major importance in the cardioprotective effects observed in the sevoflurane and desflurane groups, one would expect this effect also to be present in the propofol group, which was not the case in our study protocol.Different research groups have demonstrated that propofol has antioxidant activity and may even inhibit tumor necrosis factor α–induced human (umbilical vein) endothelial cell apoptosis, 2but the clinical relevance of these properties for myocardial protection remains to be established. Until now, all data published on the cardioprotective effects of propofol were obtained at higher concentrations than those used in clinical practice. For example, the cardioprotective effects observed by Ko et al. 3were obtained at propofol concentrations of 100 μm. Similarly, in the study of Xia et al. 4in isolated rat hearts, the enhanced ischemic tolerance of middle-aged rats was observed with a propofol perfusion at 12 μg/ml during the first 15 min of reperfusion, which was subsequently reduced to 5 μg/ml. Ebel et al. , 5on the contrary, found no effect of propofol on reperfusion injury when it was administered at concentrations of 1 μg/ml.The pathophysiology of myocardial reperfusion injury is extremely complex, with several pathways involved, ultimately resulting in myocardial dysfunction. As such, it is conceivable that different therapeutic interventions may act at different levels and have an additive cardioprotective effect. In addition to their pharmacologic preconditioning effect, volatile anesthetics also seem to have cardioprotective effects when administered only during the reperfusion period. 6,7Although the underlying mechanisms for these effects remain to be elucidated, there is now evidence that a reduction in postischemic adhesion of neutrophils may be involved. 8,9At the moment, it remains an open question how all these experimental observations may translate to clinical pathophysiology and even more to clinical treatment of myocardial ischemia–reperfusion injury.Therefore, although it is conceptually attractive, the hypothesis proposed by Drs. Xia and Luo lacks experimental and clinical evidence. To date, there are indeed no published data available supporting the hypothesis that the administration of propofol as a sedative in the intensive care unit contributes to the cardioprotective effects of peri-operatively administered sevoflurane and desflurane. Elucidation of this question would require a study protocol comparing sedation in the intensive care unit with propofol to another sedative agent without antioxidant properties.

Effects of volatile anaesthetic agents on enhanced airway tone in sensitized guinea pigs

Although volatile anaesthetics afford protection against bronchospasm, their potential to reverse a sustained constriction of hyperreactive airways has not been characterized. Accordingly, we investigated the ability of halothane, isoflurane, sevoflurane and desflurane to reverse lung constriction induced by prolonged stimulation of the muscarinic receptors in guinea pigs sensitized to ovalbumin. Pulmonary input impedance (ZL) was measured using forced oscillations in five groups of ovalbumin-sensitized, mechanically ventilated guinea pigs. ZL was measured under baseline conditions, during steady-state bronchoconstriction induced by an i.v. infusion of methacholine (MCh), and after administration of one of the volatile agents at 1 MAC after the induction of a steady-state bronchoconstriction. Airway resistance (Raw), and parenchymal tissue resistive and elastic coefficients were extracted from ZL by model fitting. All four volatile agents exhibited an initial relaxation of the MCh-induced airway constriction followed by gradual increases in Raw. The bronchodilatory effect of isoflurane was the most potent (-28.9 (SE 5.5)% at 2 min, P<0.05) and lasted longest (7 min); sevoflurane and halothane had shorter and more moderate effects (-21.1 (3.9)%, P<0.05, and -6.1 (1.7)%, P<0.05, respectively, at 1 min). Desflurane caused highly variable changes in Raw, with a tendency to enhance airway tone. Volatile agents can reverse sustained MCh-induced airway constriction only transiently in sensitized guinea pigs. Isoflurane proved most beneficial in temporally improving lung function in the presence of a severe constriction of allergic inflamed airways. Desflurane displayed potential to induce further airway constriction.

Pre- and postsynaptic volatile anaesthetic actions on glycinergic transmission to spinal cord motor neurons.

1. A common anaesthetic endpoint, prevention of withdrawal from a noxious stimulus, is determined primarily in spinal cord, where glycine is an important inhibitory transmitter. To define pre- and postsynaptic anaesthetic actions at glycinergic synapses, the effects of volatile anaesthetic agents on spontaneous and evoked glycinergic currents in spinal cord motor neurons from 6 - 14-day old rats was investigated. 2. The volatile anaesthetic agents enflurane, isoflurane and halothane significantly increased the frequency of glycinergic mIPSCs, enflurane to 190.4% of control+/-22.0 (mean+/-s.e.m., n=7, P<0.01), isoflurane to 199.0%+/-28.8 (n=7, P<0.05) and halothane to 198.2%+/-19.5 (n=7, P<0.01). However without TTX, isoflurane and halothane had no significant effect and enflurane decreased sIPSC frequency to 42.5% of control+/-12.4 (n=6, P<0.01). All the anaesthetics prolonged the decay time constant (tau) of both spontaneous and glycine-evoked currents without increasing amplitude. With TTX total charge transfer was increased; without TTX charge transfer was unchanged (isoflurane and halothane) or decreased (enflurane). 3. Enflurane-induced mIPSC frequency increases were not significantly affected by Cd(2+) (50 microM), thapsigargin (1 - 5 microM), or KB-R7943 (5 microM). KB-R7943 and thapsigargin together abolished the enflurane-induced increase in mIPSC frequency. 4. There are opposing facilitatory and inhibitory actions of volatile anaesthetics on glycine release dependent on calcium homeostatic mechanisms and sodium channels respectively. Under normal conditions (no TTX) the absolute amount of glycinergic inhibition does not increase. The contribution of glycinergic inhibition to anaesthesia may depend on its duration rather than its absolute magnitude.

Effect of anesthetics on the self-sustained oscillation in an artificial membrane induced by repetitive conformational change of DOPH molecules between hydrophilic and hydrophobic phases

The mechanism of anesthesia was approached from a study of an artificial excitable membrane that well reproduced the active electrical properties of the nerve membrane. Self-sustained oscillations of the membrane potential in a model membrane in which dioleyl phosphate (DOPH) was infiltrated into the pores of a millipore filter were utilized to investigate the effect of volatile anesthetic agents on the repetitive conformational change of DOPH molecules between hydrophilic multibilayers and hydrophobic oil droplets, while this process was coupled with diffusion of K+ across the membrane placed between KCl aqueous solutions. The period of the self-sustained oscillations increased due to the addition of volatile anesthetics to the aqueous solutions, and there were critical values of concentrations of volatile anesthetics above which the self-sustained oscillations disappeared. The volatile anesthetic agents affected the hydrophobic oil droplets of the DOPH molecules and impeded their repetitive conformational change between the hydrophilic and hydrophobic phases, just as local anesthetics had been reported to do.

The effects of volatile anaesthetic agents on human immune system function via occupational exposure.

The immunological status of individuals occupationally exposed to low levels of halothane and nitrous oxide has been examined and compared with that of non-exposed controls. No differences in the serum concentrations of IgG, IgM, IgA, peripheral blood lymphocytes and lymphocyte subpopulations between the groups were observed.

The Effect of Volatile Anesthetic Agents Upon the Conductivity of Anesthetic Circuits

*Department of Anesthesiology, Mount Sinai School of Medicine of the City University of New York, New York, New York 10029. Reprint requests to Robert B. Roberts M.D.

The effect of volatile anesthetic agents on neuromuscular transmission.

The effect of volatile anesthetic agents on neuromuscular transmission.