How to Personalize General Anesthesia-A Prospective Theoretical Approach to Conformational Changes of Halogenated Anesthetics in Fire Smoke Poisoning.

Smoke intoxication is a central event in mass burn incidents, and toxic smoke acts at different levels of the body, blocking breathing and oxygenation. The majority of these patients require early induction of anesthesia to preserve vital functions. We studied the influence of hemoglobin (HMG) and myoglobin (MGB) blockade by hydrochloric acid (HCl) in an interaction model with gaseous anesthetics using molecular docking techniques. In the next part of the study, molecular dynamics (MD) simulations were performed on the top-scoring ligand-receptor complexes to investigate the stability of the ligand-receptor complexes and the interactions between ligands and receptors in more detail. Through docking analysis, we observed that hemoglobin creates more stable complexes with anesthetic gases than myoglobin. Intoxication with gaseous hydrochloric acid produces conformational and binding energy changes of anesthetic gases to the substrate (both the pathway and the binding site), the most significant being recorded in the case of desflurane and sevoflurane, while for halothane and isoflurane, they remain unchanged. According to our theoretical model, the selection of anesthetic agents for patients affected by fire smoke containing hydrochloric acid is critical to ensure optimal anesthetic effects. In this regard, our model suggests that halothane and isoflurane are the most suitable choices for predicting the anesthetic effects in such patients when compared to sevoflurane and desflurane.

The Triple Bottom Line and Stabilization Wedges: A Framework for Perioperative Sustainability.

We present a narrative review of environmental sustainability aimed at perioperative clinicians. The review will familiarize readers with the triple bottom line framework, which aims to align the goals of delivering high-quality patient care, promoting environmental sustainability, and improving the financial position of health care organizations. We introduce the stabilization wedges model for climate change action adopted for the perioperative setting and discuss areas in which perioperative leaders can make sustainable choices. The goal of this review is to increase awareness among perioperative physicians of the environmental impacts of surgical and anesthetic care, promote engagement with sustainability efforts as a topic of professional concern for our specialty, and inspire new research in perioperative environmental sustainability.

Scientific Accuracy Matters.

The Solubility of Halothane in Blood and Tissue Homogenates. By Larson CP, Eger EI, Severinghaus JW. Anesthesiology 1962; 23:349-55. Measured samples of human and bovine blood, human hemoglobin, and tissue homogenates from human fat and both human and bovine liver, kidney, muscle, whole brain, and separated gray and white cortex were added to stoppered 2,000-ml Erlenmeyer flasks. To each flask, 0.1 ml of liquid halothane was added under negative pressure using a calibrated micropipette. After the flask was agitated for 2 to 4 h to achieve equilibrium between the gas and blood or tissue contents, a calibrated infrared halothane analyzer was used to measure the concentration of halothane vapor. Calculated partition coefficients ranged from 0.7 for water to 2.3 for blood and from 3.5 for human or bovine kidney to 6 for human whole brain or liver and 8 for human muscle. Human peritoneal fat had a value of 138. The human blood-gas partition coefficient of 2.3 as determined by this equilibration method was well below the previously published value of 3.6.

Anesthetics isoflurane and sevoflurane attenuate flagellin-mediated inflammation in the lung.

Isoflurane and sevoflurane are volatile anesthetics (VA) widely used in clinical practice to provide general anesthesia. We and others have previously shown that VAs have immunomodulatory effects and may have a significant impact on the progression of disease states. Flagellin is a component of Gram negative bacteria and plays a significant role in the pathophysiology of bacterial pneumonia through its binding to Toll-like Receptor 5 (TLR5). Our results showed that VAs, not an intravenous anesthetic, significantly attenuated the activation of TLR5 and the release of the neutrophil chemoattractant IL-8 from lung epithelial cells. Furthermore, flagellin-induced lung injury was significantly attenuated by VAs by inhibiting neutrophil migration to the bronchoalveolar space. The lungs of cystic fibrosis (CF) patients are highly colonized by Pseudomonas aeruginosa, which causes inflammation. The retrospective study of oxygenation in patients with CF who had received VA versus intravenous anesthesia suggested that VAs might have the protective effect for gas exchange. To understand the interaction between VAs and TLR5, a docking simulation was performed, which indicated that isoflurane and sevoflurane docked into the binding interphase between TLR5 and flagellin.

From ACE to ACENO: How America's Munson added Harley's British mixture to nitrous oxide.

An Ohio dentist, Corydon Munson, patented a gasometer with an attachment for vaporizing trace amounts of volatile general anesthetics or their mixtures into unoxygenated nitrous oxide. After vaporizing a variant of George Harley's ACE mixture into nitrous oxide, Munson branded his own novel anesthetic combination as ACENO.

Emerging from tabloid scandal: Dr. U.K. Mayo's Vegetable Vapor extends nitrous oxide's anesthetic duration.

Urial K. Mayo (1816-1900) was a successful Boston dentist who was plagued by personal scandal. In 1883 he patented extending the duration of nitrous-oxide anesthesia with an alcoholic tincture of hops and poppies.

The effect of anesthetics on toll like receptor 9.

Toll like receptors (TLRs) are critical receptors to respond to danger signals, and their functions are relevant in the perioperative period. We previously reported that volatile anesthetics directly bound to TLR2 and TLR4 and attenuated their functions. Given that TLR9 can respond to mitochondrial DNA, a danger signal that is released upon tissue injury, we examined the role of anesthetics on TLR9 function. Our reporter assay showed that volatile anesthetics isoflurane and sevoflurane increased the activation of TLR9, while propofol attenuated it. TLR9 activation occurs via its dimerization. The dimerization is facilitated by unmethylated cytosine-phosphate-guanine (CpG) DNA as well as DNA containing cytosine at the second position from 5'-end (5'-xCx DNA). Our structural analysis using photoactivable anesthetics and rigid docking simulation showed that isoflurane and sevoflurane bound to both TLR9 dimer interface and 5'-xCx DNA binding site. Propofol bound to the TLR9 antagonist binding site. This is the first illustration that anesthetics can affect the binding of nucleic acids to their receptor. This study sets the foundation for the effect of anesthetics on TLR9 and will pave the way for future studies to determine the significance of such interactions in the clinical setting.

Environmental and economic impact of using increased fresh gas flow to reduce carbon dioxide absorbent consumption in the absence of inhalational anaesthetics.

BACKGROUND: Increasing fresh gas flow (FGF) to a circle breathing system reduces carbon dioxide (CO2) absorbent consumption. We assessed the environmental and economic impacts of this trade-off between gas flow and absorbent consumption when no inhalational anaesthetic agent is used. METHODS: A test lung with fixed CO2 inflow was ventilated via a circle breathing system of an anaesthetic machine (Dräger Primus or GE Aisys CS2) using an FGF of 1, 2, 4, or 6 L min-1. We recorded the time to exhaustion of the CO2 absorbent canister, defined as when inspired partial pressure of CO2 exceeded 0.3 kPa. For each FGF, we calculated the economic costs and the environmental impact associated with the manufacture of the CO2 absorbent canister and the supply of medical air and oxygen. Environmental impact was measured in 100 yr global-warming potential, analysed using a life cycle assessment 'cradle to grave' approach. RESULTS: Increasing FGF from 1 to 6 L min-1 was associated with up to 93% reduction in the combined running cost with minimal net change to the 100 yr global-warming potential. Most of the reduction in cost occurred between 4 and 6 L min-1. Removing the CO2 absorbent from the circle system, and further increasing FGF to control CO2 rebreathing, afforded minimal further economic benefit, but more than doubled the global-warming potential. CONCLUSIONS: In the absence of inhalational anaesthetic agents, increasing FGF to 6 L min-1 reduces running cost compared with lower FGFs, with minimal impact to the environment.

New Method of Destroying Waste Anesthetic Gases Using Gas-Phase Photochemistry.

BACKGROUND: The inhalation anesthetics are potent greenhouse gases. To reduce the global environmental impact of the health care sector, technologies are sought to limit the release of waste anesthetic gas into the atmosphere. METHODS: Using a photochemical exhaust gas destruction system, removal efficiencies for nitrous oxide, desflurane, and sevoflurane were measured at various inlet concentrations (25% and 50%; 1.5%, 3.0%, and 6.0%; and 0.5%, 1.0%, and 2.0%, respectively) with flow rates ranging from 0.25 to 2.0 L/min. To evaluate the economic competitiveness of the anesthetic waste gas destruction system, its price per ton of carbon dioxide equivalent was calculated and compared to other greenhouse gas abatement technologies and current market prices. RESULTS: All inhaled anesthetics evaluated demonstrate enhanced removal efficiencies with decreasing flow rates (P < .0001). Depending on the anesthetic and its concentration, the photochemical exhaust gas destruction system exhibits a constant first-order removal rate, k. However, there was not a simple relation between the removal rate k and the species concentration. The costs for removing a ton of carbon dioxide equivalents are <$0.005 for desflurane, <$0.114 for sevoflurane, and <$49 for nitrous oxide. CONCLUSIONS: Based on this prototype study, destroying sevoflurane and desflurane with this photochemical anesthetic waste gas destruction system design is efficient and cost-effective. This is likely also true for other halogenated inhalational anesthetics such as isoflurane. Due to differing chemistry of nitrous oxide, modifications of this prototype photochemical reactor system are necessary to improve its removal efficiency for this gas.

Predicting cost of inhalational anesthesia at low fresh gas flows: impact of a new generation carbon dioxide absorbent.

It is well known that low fresh gas flows result in lower cost of inhalational agents. A new generation of carbon dioxide absorbents allows low flow anesthesia with all anesthetics but these new compounds are more expensive. This study examines the cost of inhalational anesthesia at different fresh gas flows combined with the cost of absorbent. The cost of sevoflurane and desflurane is lower at low fresh gas flows. Paradoxically the cost of isoflurane is cheaper at 2 L/min than at lower fresh gas flows due to increased cost of carbon dioxide absorbent. Therefore low fresh gas flows should be used when feasible with sevoflurane and desflurane, but higher fresh gas flows up to 2 L/min may be more economical with isoflurane during maintenance phase of anesthesia.

Is it time to stop using desflurane?

Desflurane has a carbon equivalence 20 times greater than sevoflurane. This article discusses alternative anaesthetic techniques, including sevoflurane, xenon, total intravenous anaesthesia and regional techniques, and methods of reducing venting of gases, which might lower the environmental impact of anaesthesia.

Isoflurane increases cell membrane fluidity significantly at clinical concentrations.

There is an on-going debate whether anesthetic drugs, such as isoflurane, can cause meaningful structural changes in cell membranes at clinical concentrations. In this study, the effects of isoflurane on lipid membrane fluidity were investigated using fluorescence anisotropy and spectroscopy. In order to get a complete picture, four very different membrane systems (erythrocyte ghosts, a 5-lipid mixture that mimics brain endothelial cell membrane, POPC/Chol, and pure DPPC) were selected for the study. In all four systems, we found that fluorescence anisotropies of DPH-PC, nile-red, and TMA-DPH decrease significantly at the isoflurane concentrations of 1 mM and 5 mM. Furthermore, the excimer/monomer (E/M) ratio of dipyrene-PC jumps immediately after the addition of isoflurane. We found that isoflurane is quite effective to loosen up highly ordered lipid domains with saturated lipids. Interestingly, 1 mM isoflurane causes a larger decrease of nile-red fluorescence anisotropy in erythrocyte ghosts than 52.2 mM of ethanol, which is three times the legal limit of blood alcohol level. Our results paint a consistent picture that isoflurane at clinical concentrations causes significant and immediate increase of membrane fluidity in a wide range of membrane systems.

[Climate footprint of halogenated inhalation anesthetics]. / Klimateffekterna från anestesin kan minska.

This study estimated the climate footprint of halogenated inhalation anesthetics in Sweden and estimated effects of a decreased use of these compounds. We collected data on sales of desflurane, sevoflurane and isoflurane in Sweden during 2017 and calculated the mass of CO2 equivalents (CO2e) using Global Warming Potential data over 100 years for the compounds. Inhalation anesthetics contributed by 5000 tons of CO2e which corresponds to 0.005 percent of the Swedish climate footprint. By replacing desflurane with sevoflurane the footprint can be reduced by 73 percent. By replacing sevoflurane with intravenous propofol the climate effect can be reduced further by at least 2 orders of magnitude.

Preparation of anaesthesia workstation for trigger-free anaesthesia: An observational laboratory study.

BACKGROUND: Trigger-free anaesthesia is required for patients who are susceptible to malignant hyperthermia. Therefore, all trace of volatile anaesthetics should be removed from anaesthetic machines before induction of anaesthesia. Because the washout procedure is time consuming, activated charcoal filters have been introduced, but never tested under minimal flow conditions. OBJECTIVE: To investigate performance of activated charcoal filters during long duration (24 h) simulated ventilation. DESIGN: A bench study. SETTING: A Primus anaesthesia machine (Dräger) was contaminated with either 4% sevoflurane or 8% desflurane by ventilating a test lung for 90 min. The machine was briefly flushed according to manufacturer instructions, activated charcoal filters were inserted and a test lung was ventilated in a 24 h test. Trace gas concentrations were measured using a closed gas loop high-resolution ion mobility spectrometer with gas chromatographic preseparation. During the experiment reduced fresh gas flows were tested. At the end of each experiment the activated charcoal filters were removed and the machine was set to standby for 10 min to test for residual contamination within the circuit. The activated charcoal filters were reconnected into the circuit to test their ability to continue removing volatile anaesthetics (functional test) from the gas. Control experiments were conducted without activated charcoal filters. MAIN OUTCOME MEASURES: Absolute concentrations of desflurane and sevoflurane. RESULTS: The concentration of volatile anaesthetics dropped to less than 5 ppm (parts per million) following insertion of activated charcoal filters. In the desflurane experiments at least 1 l min FGF was needed to keep the concentration below an acceptable level (<5 ppm): 0.5 l min fresh gas flow was required in sevoflurane experiments. While activated charcoal filters in the sevoflurane tests passed the functional test after 24 h, activated charcoal filters in the desflurane tests failed. CONCLUSION: Activated charcoal filters meet the requirements for trigger-free low flow (1 l min) ventilation over 24 h. Minimal flow (0.5 l min) ventilation may be possible for sevoflurane contaminated machines.

Molecular Bases for Anesthetic Agents: Halothane as a Halogen- and Hydrogen-Bond Donor.

Although instrumental for optimizing their pharmacological activity, a molecular understanding of the preferential interactions given by volatile anesthetics is quite poor. This paper confirms the ability of halothane to work as a hydrogen-bond (HB) donor and gives the first experimental proof that halothane also works as a halogen-bond (HaB) donor in the solid state and in solution. A halothane/hexamethylphosphortriamide co-crystal is described and its single-crystal X-ray structure shows short HaBs between bromine, or chlorine, and the phosphoryl oxygen. New UV/Vis absorption bands appear upon addition of diazabicyclooctane and tetra(n-butyl)ammonium iodide to halothane solutions, indicating that nitrogen atoms and anions may mediate the HaB-driven binding processes involving halothane as well. The ability of halothane to work as a bidentate/tridentate tecton by acting as a HaB and HB donor gives an atomic rationale for the eudismic ratio shown by this agent.

Kinetics of isoflurane and sevoflurane in a unidirectional displacement flow and the relevance to anesthetic gas exposure by operating room personnel.

International guidelines recommend the use of ventilation systems in operating rooms to reduce the concentration of potentially hazardous substances such as anesthetic gases. The exhaust air grilles of these systems are typically located in the lower corners of the operating room and pick up two-thirds of the air volume, whereas the final third is taken from near the ceiling, which guarantees an optimal perfusion of the operating room with a sterile filtered air supply. However, this setup is also employed because anesthetic gases have a higher molecular weight than the components of air and should pool on the floor if movement is kept to a minimum and if a ventilation system with a unidirectional displacement flow is employed. However, this anticipated pooling of volatile anesthetics at the floor level has never been proven. Thus, we herein investigated the flow behaviors of isoflurane, sevoflurane, and carbon dioxide (for comparison) in a measuring chamber sized 2.46 × 1.85 × 5.40 m with a velocity of 0.3 m/sec and a degree of turbulence <20%. Gas concentrations were measured at 1,728 measuring positions throughout the measuring chamber, and the flow behaviors of isoflurane and sevoflurane were found to be similar, with an overlap of 90%. The largest spread of both gases was 55 cm at 5.4 m from the emission source. Interestingly, neither isoflurane nor sevoflurane was detected at floor level, but a continuous cone-like spreading was observed due to gravity. In contrast, carbon dioxide accumulated at floor level in the form of a gas cloud. Thus, floor level exhaust ventilation systems are likely unsuitable for the collection and removal of anesthetic gases from operating rooms.