Inhaled volatile anesthetic gas for severe bronchospasm in the emergency department.

Bronchospasm is caused by reversible constriction of the smooth muscles of the bronchial tree. This causes obstruction of the lower airways, which is commonly seen at the emergency department (ED) in patients with acute exacerbation of asthma or chronic obstructive pulmonary disease. Ventilation may be difficult in mechanically intubated patients with severe bronchospasm due to airflow limitation, air trapping, and high airway resistance. The beneficial effects of volatile inhaled anesthetic gas had been reported due to its bronchodilation properties. In this case series, we would like to share our experience delivering inhaled volatile anesthetic gas via a conserving device for three patients with refractory bronchospasm at the ED. Inhaled anesthetic gas is safe, feasible and should be considered as an alternative rescue therapy for ventilated patients with severe lower airway obstruction.

Isoflurane attenuates sepsis-associated lung injury.

Acute lung injury is one of major complications associated with sepsis, responsible for morbidity and mortality. Patients who suffer from acute lung injury often require respiratory support under sedations, and it would be important to know the role of sedatives in lung injury. We examined volatile anesthetic isoflurane, which is commonly used in surgical setting, but also used as an alternative sedative in intensive care settings in European countries and Canada. We found that isoflurane exposure attenuated neutrophil recruitment to the lungs in mice suffering from experimental polymicrobial abdominal sepsis. We found that isoflurane attenuated one of major neutrophil chemoattractants LTB4 mediated response via its receptor BLT1 in neutrophils. Furthermore, we have shown that isoflurane directly bound to BLT1 by a competition assay using newly developed labeled BLT1 antagonist, suggesting that isoflurane would be a BLT1 antagonist.

Volatile anesthetic gas concentration sensing using flow sensor fusion for use in Austere settings.

Flow sensors are often sensitive to the presence of volatile anesthetics. However, this sensitivity provides a unique opportunity to combine flow sensors of differing technological principles as an alternative to measuring volatile anesthetic gas concentration, particularly for austere settings. To determine the feasibility of flow sensor fusion for volatile anesthetic concentrations monitoring, eight flow sensors were tested with isoflurane, sevoflurane, and desflurane, ranging in concentrations from 0-4.5%, 0-3.5%, and 0-18%, respectively. Pairs of flow sensors were fit to the volatile anesthetic gas concentration with a leave-one-out cross-validation method to reduce the likelihood of overfitting. Bland-Altman was used for the final evaluation of sensor pair performance. Several sensor pairs yielded limits of agreement comparable to the rated accuracy of a commercial infrared spectrometer. The ultrasonic and orifice-plate flowmeters yielded the most combinations of viable sensor pairs for all three volatile anesthetic gases. Conclusion: Measuring volatile anesthetic gases using flow sensor fusion is a feasible low-cost, low-maintenance alternative to infrared spectroscopy. In this study, testing was done under steady-state conditions in 100% oxygen. Further testing is necessary to ensure sensor fusion performance under conditions that are more reflective of the clinical use case.

The Role of Anesthetic Management in Surgical Site Infections After Pediatric Intestinal Surgery.

BACKGROUND: Although surgical site infections (SSIs) remain a significant health care issue, a limited number of studies have analyzed risk factors for SSIs in children, particularly the role of intraoperative anesthetic management. Pediatric patients are less likely to have major adult risk factors for SSIs such as smoking and diabetes. Thus children may be more suitable as a cohort for examining the role of intraoperative anesthetics in SSIs. AIM: We examined an association between SSI incidence and anesthetic management in children who underwent elective intestinal surgery in a single institution. METHODS: We performed a retrospective study of 621 patients who underwent elective intestinal surgery under general anesthesia between January 2017 and September 2019, with primary outcome as the incidence of SSIs. We compared patients who were dichotomized in accordance with the median of the sevoflurane dose. We used propensity score (PS) pairwise matching of these patients to avoid selection biases. PS matching yielded 204 pairs of patients. RESULTS: We found that higher doses of sevoflurane were associated with a higher incidence of SSIs (9.8% versus 3.9%, P = 0.019). We adjusted for intraoperative factors that were not included in the PS adjustment factors, and multivariate regression analysis after PS matching showed compatible results (odds ratio: 2.58, 95% confidence interval: 1.11-6.04, P = 0.028). CONCLUSIONS: Higher doses of sevoflurane are associated with increased odds of SSIs after pediatric elective intestinal surgery. A randomized controlled study of volatile anesthetic-based versus intravenous anesthetic-based anesthesia will be needed to further determine the role of anesthetic drugs in SSI risk.

Cardiothoracic Anesthesia and Critical Care in the United Kingdom (UK) Part 1: Some Insights Into the History and Development.

This review is intended to highlight some of the historic events that contributed to the development of thoracic and cardiac anesthesia and surgery in Great Britain and Northern Ireland (UK). The aim of this first of two parts is to concentrate on the development of techniques, facilities, and pharmacology that allowed progress and advancement in patient management that were developed primarily in the UK. However, progress usually requires input from a wide variety of sources of knowledge, and cardiothoracic practice is no exception. Reference is, thus, made to sources outside of the UK that guided, influenced, or inspired changes in practice, such as the techniques of operating on the heart and great vessels in war casualties, developed by Dr. Dwight Harken, or the demonstration of the Blalock-Thomas-Taussig shunt by Alfred Blalock. In addition to advances in medical equipment, such as computed tomography, the UK contributed greatly to pharmacologic interventions that were unique at the time in such varied areas as nonflammable volatile anesthetic agents, heart failure treatments, and neuromuscular blocking agents for both cardiac and thoracic surgical practice.

Volatile anesthetic agents for life-threatening pediatric asthma: A multicenter retrospective cohort study and narrative review.

BACKGROUND: Volatile anesthetic agents are described as rescue therapy for children invasively ventilated for critical asthma. Yet, data are currently limited to case series. AIMS: Using the Virtual Pediatric Systems database, we assessed children admitted to a pediatric intensive care unit invasively ventilated for life-threatening asthma and hypothesized ventilation duration and mortality rates would be lower for subjects exposed to volatile anesthetics compared with those without exposure. METHODS: We performed a multicenter retrospective cohort study among nine institutions including children 5-17 years of age invasively ventilated for asthma from 2013 to 2019 with and without exposure to volatile anesthetics. Primary outcomes were ventilation duration and mortality. Secondary outcomes included patient characteristics, length of stay, and anesthetic-related adverse events. A subgroup analysis was performed evaluating children intubated ≥2 days. RESULTS: Of 203 children included in study, there were 29 (14.3%) with and 174 (85.7%) without exposure to volatiles. No differences in odds of mortality (1.1, 95% CI: 0.3-3.9, p > .999) were observed. Subjects receiving volatiles experienced greater median difference in length of stay (4.8, 95% CI: 1.9-7.8 days, p < .001), ventilation duration (2.3, 95% CI: 1-3.3 days, p < .001), and odds of extracorporeal life support (9.1, 95% CI: 1.9-43.2, p = .009) than those without volatile exposure. For those ventilated ≥2 days, no differences were detected in mortality, ventilation duration, length of stay, arrhythmias, or acute renal failure. However, the odds of extracorporeal life support remained greater for those receiving volatiles (7.6, 95% CI: 1.3-44.5, p = .027). No children experienced malignant hyperthermia or hepatic failure after volatile exposure. CONCLUSIONS: For intubated children for asthma, no differences in mechanical ventilation duration or mortality between those with and without volatile anesthetic exposure were observed. Although volatiles may represent a viable rescue therapy for severe cases of asthma, definitive, and prospective trials are still needed.

The effect of intravenous lidocaine infusion on bispectral index during major abdominal surgery.

Intraoperative lidocaine infusion has become widely accepted as an adjunct to general anesthesia where its use has been associated with opioid-sparing and enhanced recovery. The aims of this study were to determine whether or not intravenous (IV) lidocaine infusion (a) has an anesthetic sparing effect during major colorectal procedures and (b) if it also affects level of hypnosis as measured by bispectral index (BIS). Twenty-five patients undergoing laparotomy for resection of colorectal tumours were randomized to receive either IV lidocaine (1.5 mg kg-1 bolus then 1 mg kg-1 per hour) or an equivalent volume of normal saline commenced after intravenous induction of general anesthesia. Anesthesia was maintained with volatile anesthetic agent combined with intermittent IV fentanyl titrated to hemodynamic stability. Minimum alveolar concentration (MAC) of volatile was calculated using an age-adjusted algorithm (corrected MAC). BIS values were recorded throughout; however, treating anesthesiologists were blinded to BIS values and hence they were not used to guide depth of anesthesia. No other regional anesthesia techniques were used. During the maintenance phase of anesthesia, corrected MAC of volatile agent was lower (1.0 versus 1.1, p = 0.003); whereas BIS values were higher (45 versus 39, p < 0.001) in patients who received lidocaine versus placebo. No differences in mean arterial pressure (80 versus 80 mmHg, p = 0.796) or total fentanyl dose (538 versus 444 mcg, p = 0.24) were observed between the two groups. Heart rate was slightly higher in patients who received lidocaine versus placebo (67 versus 64 bpm, p = 0.001). Lidocaine infusion resulted in mean plasma levels of 1.7 mcg ml-1 (1.3-2.0 mcg ml-1, 95% CI). Our results support an anesthetic sparing effect of lidocaine infusion indicated by lower MAC requirements. Higher BIS values in the lidocaine versus placebo group may indicate that levels of hypnosis were not equivalent. Alternatively, BIS may not be a sensitive indicator of synergistic interactions between local anesthetic and volatile agent. Our results advocate a cautious approach to titration of general anesthesia when combined with lidocaine infusion.

An Unusual Complication With the Administration of a Volatile Anesthetic Agent for Status Asthmaticus in the Pediatric Intensive Care Unit: Case Report and Review of the Literature.

In severe cases of status asthmaticus, when conventional therapies fail, volatile anesthetic agents remain a therapeutic option. When delivered outside of the operating room setting, specialized delivery techniques are needed to ensure the safe and effective use of volatile anesthetic agents. We present a 16-year-old adolescent with status asthmaticus who required the therapeutic administration of the volatile anesthetic agent, sevoflurane, in the pediatric intensive care unit (PICU). Although initially effective in reducing bronchospasm, progressive hypercarbia developed due to defective functioning of the carbon dioxide absorber of the anesthesia machine. This failure occurred as the soda lime compartment filled with water accumulated from circuit humidification and continuous albuterol therapy. The role of volatile anesthetic agents in the treatment of status asthmaticus in the PICU is discussed, options for delivery outside of the operating room presented, and potential problems with delivery reviewed.

Comparison of the Analgesic Properties of Sevoflurane and Desflurane Using Surgical Pleth Index at Equi-Minimum Alveolar Concentration.

Background: Traditionally, minimum alveolar concentration (MAC) has been used as the standard measure to compare the potencies of volatile anesthetics. However, it reflects the spinal mechanism of immobility rather than the subcortical mechanism of analgesia. Recently, the surgical pleth index (SPI) derived from photoplethysmographic waveform was shown to reflect the intraoperative analgesic component. This study was designed to compare the SPI values produced by equi-MAC of two commonly used volatile anesthetics, sevoflurane and desflurane. Methods: Seventy-two patients undergoing arthroscopic shoulder surgery were randomly assigned to two groups receiving either sevoflurane (n = 36) or desflurane (n = 36). General anesthesia was maintained with the respective volatile anesthetic only. A vaporizer was adjusted to maintain end-tidal anesthetic concentration at age-corrected 1.0 MAC throughout the study period. The SPI value as an analgesic estimate and the bispectral index (BIS) value as a hypnotic estimate were recorded at predefined time points during the standardized surgical procedure. Results: During the steady state of age-corrected 1.0 MAC, mean SPI values throughout the entire study period were significantly higher in the sevoflurane group than in the desflurane group (38.1 ±â€…12.8 vs. 30.7 ±â€…8.8, respectively, P = 0.005), and mean BIS values were significantly higher in the sevoflurane group than in the desflurane group (40.7 ±â€…5.8 vs. 36.8 ±â€…6.2, respectively, P = 0.008). Conclusions: Equi-MAC of sevoflurane and desflurane did not produce similar surgical pleth index values. Therefore, sevoflurane and desflurane may have different analgesic properties at equipotent concentrations.

A clinical review of inhalation anesthesia with sevoflurane: from early research to emerging topics.

A large number of studies during the past two decades have demonstrated the efficacy and safety of sevoflurane across patient populations. Clinical researchers have also investigated the effects of sevoflurane, its hemodynamic characteristics, its potential protective effects on several organ systems, and the incidence of delirium and cognitive deficiency. This review examines the clinical profiles of sevoflurane and other anesthetic agents, and focuses upon emerging topics such as organ protection, postoperative cognitive deficiency and delirium, and novel ways to improve postanesthesia outcomes.

Attenuation of Isoflurane Preconditioning-Induced Acute Cardioprotection in Hypertensive Hypertrophied Hearts.

OBJECTIVES: To evaluate the efficiency of isoflurane-induced anesthetic preconditioning and the role of mitochondrial manganese superoxide dismutase (MnSOD) in hypertensive hypertrophied hearts. DESIGN: A prospective animal investigation. SETTING: Medical center hospital research laboratory. PARTICIPANTS: Male spontaneously hypertensive rats (SHRs) and normotensive control Wistar-Kyoto (WKY) rats. INTERVENTIONS: All pentobarbital-anesthetized open-chest rats were subjected to a 45-minute left coronary artery occlusion followed by a 120-minute reperfusion. Before ischemia, both SHR and WKY rats were assigned randomly to receive a 30-minute exposure to 0.9% saline or 1.0 minimum alveolar concentration isoflurane. MEASUREMENTS AND MAIN RESULTS: The myocardial infarct size, assessed as a percentage of the area at risk, was significantly greater in the hypertrophied SHRs than in the WKY rats (65.3%±8.7% v 51.8%±7.2%, p<0.05). Isoflurane preconditioning appreciably reduced the infarct size in the WKY hearts (30.9%±10.5%, p<0.05) but not in the SHR hearts. MnSOD protein expression and enzymatic activity were increased drastically in response to isoflurane exposure in the hearts of the WKY rats (p<0.05) but not in the SHRs. CONCLUSIONS: Isoflurane-induced anesthetic preconditioning is attenuated in hypertensive hypertrophied hearts. This impairment may be associated with the loss of MnSOD augmentation during ischemia and reperfusion.

Sevoflurane Preconditioning Confers Neuroprotection via Anti-apoptosis Effects.

Neuroprotection against cerebral ischemia afforded by volatile anesthetic preconditioning (APC) has been demonstrated both in vivo and in vitro, yet the underlying mechanism is poorly understood. We previously reported that repeated sevoflurane APC reduced infarct size in rats after focal ischemia. In this study, we investigated whether inhibition of apoptotic signaling cascades contributes to sevoflurane APC-induced neuroprotection. Male Sprague-Dawley rats were exposed to ambient air or 2.4 % sevoflurane for 30 min per day for 4 consecutive days and then subjected to occlusion of the middle cerebral artery (MCAO) for 60 min at 24 h after the last sevoflurane intervention. APC with sevoflurane markedly decreased apoptotic cell death in rat brains, which was accompanied by decreased caspase-3 cleavage and cytochrome c release. The apoptotic suppression was associated with increased ratios of anti-apoptotic Bcl-2 family proteins over pro-apoptotic proteins and with decreased activation of JNK and p53 pathways. Thus, our data suggest that suppression of apoptotic cell death contributes to the neuroprotection against ischemic brain injury conferred by sevoflurane preconditioning.

Isoflurane modulates cardiac mitochondrial bioenergetics by selectively attenuating respiratory complexes.

Mitochondrial dysfunction contributes to cardiac ischemia-reperfusion (IR) injury but volatile anesthetics (VA) may alter mitochondrial function to trigger cardioprotection. We hypothesized that the VA isoflurane (ISO) mediates cardioprotection in part by altering the function of several respiratory and transport proteins involved in oxidative phosphorylation (OxPhos). To test this we used fluorescence spectrophotometry to measure the effects of ISO (0, 0.5, 1, 2mM) on the time-course of interlinked mitochondrial bioenergetic variables during states 2, 3 and 4 respiration in the presence of either complex I substrate K(+)-pyruvate/malate (PM) or complex II substrate K(+)-succinate (SUC) at physiological levels of extra-matrix free Ca(2+) (~200nM) and Na(+) (10mM). To mimic ISO effects on mitochondrial functions and to clearly delineate the possible ISO targets, the observed actions of ISO were interpreted by comparing effects of ISO to those elicited by low concentrations of inhibitors that act at each respiratory complex, e.g. rotenone (ROT) at complex I or antimycin A (AA) at complex III. Our conclusions are based primarily on the similar responses of ISO and titrated concentrations of ETC. inhibitors during state 3. We found that with the substrate PM, ISO and ROT similarly decreased the magnitude of state 3 NADH oxidation and increased the duration of state 3 NADH oxidation, ΔΨm depolarization, and respiration in a concentration-dependent manner, whereas with substrate SUC, ISO and ROT decreased the duration of state 3 NADH oxidation, ΔΨm depolarization and respiration. Unlike AA, ISO reduced the magnitude of state 3 NADH oxidation with PM or SUC as substrate. With substrate SUC, after complete block of complex I with ROT, ISO and AA similarly increased the duration of state 3 ΔΨm depolarization and respiration. This study provides a mechanistic understanding in how ISO alters mitochondrial function in a way that may lead to cardioprotection.

Use of volatile anesthetics during cardiopulmonary bypass: a systematic review of adverse events.

OBJECTIVES: Recently, evidence of reduction in mortality due to the use of volatile agents during cardiac surgery led to an increase in their use during cardiopulmonary bypass (CPB). Because this technique could be beneficial to patients, but might present several hazards to new users, the authors decided to perform a systematic review of the main problems and complications. DESIGN: Systematic literature review. SETTING: Hospital. PARTICIPANTS: Adults undergoing cardiac surgery with use of volatile anesthetic agents during CPB. INTERVENTION: Several databases were searched for pertinent studies to identify all reports on the adverse events of using volatile agents during CPB and all randomized controlled trials using volatile agents during CPB. MEASUREMENTS AND MAIN RESULTS: Six nonrandomized trials reporting adverse events or complications with the use of volatile agents during CPB for cardiac surgery were identified: 2 reporting low transfer of isoflurane to the blood with diffusion membrane oxygenators; 2 reporting iatrogenic causes of damage after spilling liquid isoflurane onto the surface of the membrane oxygenators while filling the vaporizer; and 2 suggesting that the use of volatile agents during CPB increased the pollution of the room and the risk of occupational exposure of the operating room staff. On the other hand, no adverse event was reported in 19 studies that randomized 1,195 patients to receive isoflurane, desflurane, or sevoflurane during CPB. CONCLUSION: It is mandatory for industry to provide safe and easy-to-use devices to administer volatile agents during CPB with the standard membrane oxygenators.

Mechanism of isoflurane­mediated breast cancer growth in vivo.

Use of volatile anesthetics is associated with worse outcome following tumor resection surgery compared with the use of intravenous anesthetics. However, the underlying mechanism has not been clearly delineated yet in vivo. The EO771 cell-based congenic breast cancer model was used in the present study. Isoflurane directly binds to and inhibits two adhesion molecules, leukocyte function-associated antigen-1 (LFA-1) and macrophage-1 antigen (Mac-1). Similarly, exposure to sevoflurane, another volatile anesthetic and LFA-1 inhibitor, is associated with an increase in breast cancer size compared with non-exposure. Thus, the present study first examined the role of LFA-1 and Mac-1 in the EO771 breast cancer model. Both LFA-1 deficiency and inhibition enhanced tumor growth, which was supported by cytokine and eicosanoid data profiles. By contrast, Mac-1 deficiency did not affect tumor growth. The exposure to isoflurane and sevoflurane was associated with an increase in breast cancer size compared with non-exposure. These data suggested that isoflurane enhanced tumor growth by interacting with LFA-1. Isoflurane exposure did not affect tumor growth in LFA-1-deficient mice. In summary, the present data showed that LFA-1 deficiency facilitated breast cancer growth, and isoflurane, an LFA-1 inhibitor, also increased breast cancer growth.

Veterinarians exposed to inhaled anesthetic present chromosome damage, apoptosis and cell cycle changes.

This cross-sectional study evaluated, for the first time, DNA damage, viability, and cell death of lymphocytes and cell cycle phases of mononuclear and polymorphonuclear cells in veterinarians exposed to the volatile anesthetic isoflurane. Veterinarians who were occupationally exposed to isoflurane (exposed group; n = 20) and matched-unexposed individuals (volunteers without occupational exposure; n = 20) were enrolled in the study. DNA damage was assessed in lymphocytes by micronucleus (MN) and phosphorylated histone gamma-H2AX (γ-H2AX). Cell viability, cytotoxicity, and the cell cycle were evaluated by flow cytometry. Isoflurane was detected in urine samples by headspace gas chromatography-mass spectrometry. Compared with unexposed subjects, veterinarians occupationally exposed to isoflurane (25.7 ± 23.7 µg/L urine) presented statistically higher MN frequencies, lymphocytic apoptosis rates, and numbers of polymorphonuclear cells in the G0/G1 stage. Additionally, the exposed group presented statistically lower proportions of viable lymphocytes and G2/M polymorphonuclear cells. Our findings indicate that veterinarians who are frequently exposed to inhaled anesthetic exhibit chromosomal and cell damage in addition to changes in peripheral blood cell proliferation.

Anesthetic Management and Considerations in a Rare Case of Parietal Bone Hemangioma.

Parietal bone hemangiomas represent a minority of diagnosed brain tumors. These lesions require careful management under anesthesia due to their vascularity and cranial location. We discuss a 31-year-old female with chronic headaches who underwent surgery for the removal of a large parietal bone hemangioma, necessitating considerations for stable hemodynamics, intracranial pressure (ICP), and bleeding risks. There is no standard anesthetic for these cases, so a mixed anesthetic approach was used, combining intravenous anesthesia with sevoflurane, aimed at optimizing control during the procedure.

Preventing Prolonged Times to Awakening While Mitigating the Risk of Patient Awareness: Gas Man Computer Simulations of Sevoflurane Consumption From Brief, High Fresh Gas Flow Before the End of Surgery.

Prolonged times to tracheal extubation are associated with adverse patient and economic outcomes. We simulated awakening patients from sevoflurane after long-duration surgery at 2% end-tidal concentration, 1.0 minimum alveolar concentration (MAC) in a 40-year-old. Our end-of-surgery target was 0.5 MAC, the Michigan Awareness Control Study's threshold for intraoperative alerts. Consider an anesthetist who uses a 1 liter/minute gas flow until surgery ends. During surgical closure, the inspired sevoflurane concentration is reduced from 2.05% to 0.62% (i.e., MAC-awake). The estimated time to reach 0.5 MAC is 28 minutes. From a previous study, 28 minutes exceeded ≥95% of surgical closure times for all 244 distinct surgical procedures (N=23,343 cases). Alternatively, the anesthetist uses 8 liters/minute gas flow with the vaporizer at MAC-awake for 1.8 minutes, which reduces the end-tidal concentration to 0.5 MAC. The anesthetist then increases the vaporizer to keep end-tidal 0.5 MAC until the surgery ends. An additional simulation shows that, compared with simulated end-tidal agent feedback control, this approach consumed 0.45 mL extra agent. Simulation results are the same for an 80-year-old patient. The extra 0.45 mL has a global warming potential comparable to driving 26 seconds at 40 kilometers (25 miles) per hour, comparable to route modification to avoid potential roadway hazards.