Volatile Isoflurane Research Articles

Anaesthesia by intravenous propofol reduces the incidence of intra-operative gastric electrical slow-wave dysrhythmias compared to isoflurane

Gastric motility is coordinated by bioelectrical slow-wave activity, and abnormal electrical dysrhythmias have been associated with nausea and vomiting. Studies have often been conducted under general anaesthesia, while the impact of general anaesthesia on slow-wave activity has not been studied. Clinical studies have shown that propofol anaesthesia reduces postoperative nausea and vomiting (PONV) compared with isoflurane, while the underlying mechanisms remain unclear. In this study, we investigated the effects of two anaesthetic drugs, intravenous (IV) propofol and volatile isoflurane, on slow-wave activity. In vivo experiments were performed in female weaner pigs (n = 24). Zolazepam and tiletamine were used to induce general anaesthesia, which was maintained using either IV propofol (n = 12) or isoflurane (n = 12). High-resolution electrical mapping of slow-wave activity was performed. Slow-wave dysrhythmias occurred less often in the propofol group, both in the duration of the recorded period that was dysrhythmic (propofol 14 ± 26%, isoflurane 43 ± 39%, P = 0.043 (Mann–Whitney U test)), and in a case-by-case basis (propofol 3/12, isoflurane 8/12, P = 0.015 (Chi-squared test)). Slow-wave amplitude was similar, while velocity and frequency were higher in the propofol group than the isoflurane group (P < 0.001 (Student’s t-test)). This study presents a potential physiological biomarker linked to recent observations of reduced PONV with IV propofol. The results suggest that propofol is a more suitable anaesthetic for studying slow-wave patterns in vivo.

Balanced volatile sedation with isoflurane in critically ill patients with aneurysmal subarachnoid hemorrhage - a retrospective observational study.

In patients with severe aneurysmal subarachnoid hemorrhage (SAH) deep sedation is often used early in the course of the disease in order to control brain edema formation and thus intracranial hypertension. However, some patients do not reach an adequate sedation depth despite high doses of common intravenous sedatives. Balanced sedation protocols incorporating low-dose volatile isoflurane administration might improve insufficient sedation depth in these patients. We retrospectively analyzed ICU patients with severe aneurysmal SAH who received isoflurane in addition to intravenous anesthetics in order to improve insufficient sedation depth. Routinely recorded data from neuromonitoring, laboratory and hemodynamic parameters were compared before and up to 6 days after initiation of isoflurane. Sedation depth measured using the bispectral index improved in thirty-six SAH patients (-15.16; p = 0.005) who received additional isoflurane for a mean period of 9.73 ± 7.56 days. Initiation of isoflurane sedation caused a decline in mean arterial pressure (-4.67 mmHg; p = 0.014) and cerebral perfusion pressure (-4.21 mmHg; p = 0.013) which had to be balanced by increased doses of vasopressors. Patients required increased minute ventilation in order to adjust for the increase in PaCO2 (+2.90 mmHg; p < 0.001). We did not detect significant increases in mean intracranial pressure. However, isoflurane therapy had to be terminated prematurely in 25% of the patients after a median of 30 h due to episodes of intracranial hypertension or refractory hypercapnia. A balanced sedation protocol including isoflurane is feasible for SAH patients experiencing inadequately shallow sedation. However, therapy should be restricted to patients without impaired lung function, hemodynamic instability and impending intracranial hypertension.

Protective Effect of Oxygen and Isoflurane in Rodent Model of Intestinal Ischemia-Reperfusion Injury.

Animal research in intestinal ischemia-reperfusion injury (IRI) is mainly performed in rodent models. Previously, intraperitoneal (I.P.) injections with ketamine-xylazine mixtures were used. Nowadays, volatile anesthetics (isoflurane) are more common. However, the impact of the anesthetic method on intestinal IRI has not been investigated. We aim to analyze the different anesthetic methods and their influence on the extent of intestinal IRI in a rat model. Male Sprague-Dawley rats were used to investigate the effect of I.P. anesthesia on 60 min of intestinal ischemia and 60 min of reperfusion in comparison to hyperoxygenation (100% O2) and volatile isoflurane anesthesia. In comparison to I.P. anesthesia with room air (21% O2), supplying 100% O2 improved 7-day survival by cardiovascular stabilization, reducing lactic acidosis and preventing vascular leakage. However, this had no effect on the intestinal epithelial damage, permeability, and inflammatory response observed after intestinal IRI. In contrast to I.P. + 100% O2, isoflurane anesthesia reduced intestinal IRI by preventing ongoing low-flow reperfusion hypotension, limiting intestinal epithelial damage and permeability, and by having anti-inflammatory effects. When translating the aforementioned results of this study to clinical situations, such as intestinal ischemia or transplantation, the potential protective effects of hyperoxygenation and volatile anesthetics require further research.

Isoflurane sedation in patients undergoing VA-ECMO treatment for cardiogenic shock

Abstract Funding Acknowledgements Type of funding sources: None. Objectives (Background): The feasibility and hemodynamic effects of isoflurane sedation in cardiogenic shock in the presence of extracorporeal membrane oxygenation (VA-ECMO) treatment is currently unknown. Design Retrospective single-center study Patients/subjects: Cardiogenic shock patients with VA-ECMO treatment under sedation with volatile isoflurane between November 2018 and October 2019 have been enrolled in this study and were matched by propensity score in a 1:1 ratio with intravenously (IV) sedated patients treated between January 2013 and November 2018 from the cardiogenic shock registry of our university hospital. Measurements and Main Results: Isoflurane sedation was used in 32 patients with cardiogenic shock and VA-ECMO treatment. The mean age of conventionally sedated patients was 58.4 ± 13.8 years and 56.3 ± 11.5 years for patients with isoflurane sedation (p = 0.51). Administration of isoflurane was associated with lower IV sedative drug use during VA-ECMO treatment (86% vs. 32%, p = 0.01). Mean systolic arterial pressure was similar (94.3 ± 12.6 mmHg versus 92.9 ± 10.5 mmHg, p = 0.65), but mean heart rate was significantly higher in the conventional sedation group, when compared to the isoflurane group (85.2 ± 20.5 /min vs. 74.7 ± 15.0 /min; p = 0.02). Catecholamine doses, VA-ECMO blood and gas flow, ventilation time (304 ± 143 h vs. 398 ± 272 h,p = 0.16), bleeding complications BARC3a or higher (59.3% vs. 65.3%, p = 0.76) and 30 day-mortality (59.2% vs. 63.4%, p = 0.80) were similar in both groups. The overall sedation costs per patient were significantly lower in the conventional group, when compared to the isoflurane group (537 ± 624 € vs. 1280 ± 837 €, p &amp;lt; 0.001). Conclusions Volatile sedation with isoflurane is feasible – albeit at higher costs - in patients with cardiogenic shock and VA-ECMO treatment and was not associated with higher catecholamine dosage or ECMO flow rate compared to IV sedation.

Isoflurane sedation in patients undergoing VA-ECMO treatment for cardiogenic shock – an observational propensity-matched study

Abstract Introduction The feasibility and hemodynamic effects of isoflurane sedation in cardiogenic shock in the presence of extracorporeal membrane oxygenation (VA-ECMO) treatment is currently unknown. Methods Thirty-two cardiogenic shock patients with VA-ECMO treatment under sedation with volatile isoflurane on a cardiac intensive care unit have been enrolled in this retrospective single-center study and were matched by propensity score in a 1:1 ratio with intravenously (IV) sedated patients. Results Administration of isoflurane was associated with lower IV sedative drug use during VA-ECMO treatment (86% vs. 32%, p=0.01). Mean systolic arterial pressure was similar (94.3±12.6 mmHg versus 92.9±10.5 mmHg, p=0.65), but mean heart rate was significantly higher in the conventional sedation group, when compared to the isoflurane group (85.2±20.5 / min vs. 74.7±15.0 /min; p=0.02). Catecholamine doses, VA-ECMO blood and gas flow, ventilation time (304±143 h vs. 398±272 h, p=0.16), bleeding complications BARC3a or higher (59.3% vs. 65.3%, p=0.76) and 30-day mortality (59.2% vs. 63.4%, p=0.80) were similar in both groups. Conclusions Volatile sedation with isoflurane is feasible in patients with cardiogenic shock and VA-ECMO treatment and was not associated with higher catecholamine dosage or ECMO flow rate compared to IV sedation. Mortality and bleeding Funding Acknowledgement Type of funding source: None

Volatile Isoflurane in Critically Ill Coronavirus Disease 2019 Patients-A Case Series and Systematic Review.

Objectives:The ongoing coronavirus pandemic is challenging, especially in severely affected patients who require intubation and sedation. Although the potential benefits of sedation with volatile anesthetics in coronavirus disease 2019 patients are currently being discussed, the use of isoflurane in patients with coronavirus disease 2019–induced acute respiratory distress syndrome has not yet been reported.Design:We performed a retrospective analysis of critically ill patients with hypoxemic respiratory failure requiring mechanical ventilation.Setting:The study was conducted with patients admitted between April 4 and May 15, 2020 to our ICU.Patients:We included five patients who were previously diagnosed with severe acute respiratory syndrome coronavirus 2 infection.Intervention:Even with high doses of several IV sedatives, the targeted level of sedation could not be achieved. Therefore, the sedation regimen was switched to inhalational isoflurane. Clinical data were recorded using a patient data management system. We recorded demographical data, laboratory results, ventilation variables, sedative dosages, sedation level, prone positioning, duration of volatile sedation and outcomes.Measurements & Main Results:Mean age (four men, one women) was 53.0 (± 12.7) years. The mean duration of isoflurane sedation was 103.2 (± 66.2) hours. Our data demonstrate a substantial improvement in the oxygenation ratio when using isoflurane sedation. Deep sedation as assessed by the Richmond Agitation and Sedation Scale was rapidly and closely controlled in all patients, and the subsequent discontinuation of IV sedation was possible within the first 30 minutes. No adverse events were detected.Conclusions:Our findings demonstrate the feasibility of isoflurane sedation in five patients suffering from severe coronavirus disease 2019 infection. Volatile isoflurane was able to achieve the required deep sedation and reduced the need for IV sedation.

Isoflurane Sedation in Patients Undergoing Venoarterial Extracorporeal Membrane Oxygenation Treatment for Cardiogenic Shock-An Observational Propensity-Matched Study.

Objectives:The feasibility and hemodynamic effects of isoflurane sedation in cardiogenic shock in the presence of venoarterial extracorporeal membrane oxygenation treatment are currently unknown.Design:Retrospective single-center study.Setting:Cardiac ICU of Munich university hospital.Patients/Subjects:Cardiogenic shock patients with venoarterial extracorporeal membrane oxygenation treatment under sedation with volatile isoflurane between November 2018 and October 2019 have been enrolled in this study and were matched by propensity score in a 1:1 ratio with IV sedated patients treated between January 2013 and November 2018 from the cardiogenic shock registry of the university hospital of Munich.Measurements and Main Results:Isoflurane sedation was used in 32 patients with cardiogenic shock and venoarterial extracorporeal membrane oxygenation treatment. The mean age of conventionally sedated patients was 58.4 ± 13.8 years and 56.3 ± 11.5 years for patients with isoflurane sedation (p = 0.51). Administration of isoflurane was associated with lower IV sedative drug use during venoarterial extracorporeal membrane oxygenation treatment (86% vs 32%; p = 0.01). Mean systolic arterial pressure was similar (94.3 ± 12.6 vs 92.9 ± 10.5 mm Hg; p = 0.65), but mean heart rate was significantly higher in the conventional sedation group, when compared with the isoflurane group (85.2 ± 20.5 vs 74.7 ± 15.0 beats/min; p = 0.02). Catecholamine doses, venoarterial extracorporeal membrane oxygenation blood and gas flow, ventilation time (304 ± 143 vs 398 ± 272 hr; p = 0.16), bleeding complications bleeding academic research consortium 3a or higher (59.3% vs 65.3%; p = 0.76), and 30-day mortality (59.2% vs 63.4%, p = 0.80) were similar in both groups. The overall sedation costs per patient were significantly lower in the conventional group, when compared with the isoflurane group (537 ± 624 vs 1280 ± 837 €; p < 0.001).Conclusions:Volatile sedation with isoflurane is feasible—albeit at higher costs—in patients with cardiogenic shock and venoarterial extracorporeal membrane oxygenation treatment and was not associated with higher catecholamine dosage or extracorporeal membrane oxygenation flow rate compared with IV sedation.

Isoflurane or propofol sedation in patients with targeted temperature management after cardiopulmonary resuscitation: A single center study

ProposeTargeted temperature management improves outcomes in comatose patients after cardiac arrest. Short lasting sedatives might enable rapid awakening after targeted temperature management and therefore early prognostication and extubation. Aim of the present study was to compare sedation with volatile isoflurane to intravenous propofol. Materials and methodsAll patients after cardiopulmonary resuscitation undergoing targeted temperature management treated between 01/2014 and 02/2017 at a single tertiary referral hospital were screened. Exclusion criteria included extracorporeal support or a survival below 48 h. ResultsData on 214 patients (median age 66.1 years, 62.6% shockable rhythm, survival 69.6%) are reported, 178 patients on propofol and sufentanil and 36 patients on isoflurane and sufentanil. Median time to first spontaneous breathing (9.3 h vs. 9.5 h, p = .373), median duration on mechanical ventilation in extubated patients (99.4 h vs. 105.7 h, p = .692) and median ICU stay (11.1d vs. 9.8d, p = .320) were similar in patients on propofol or isoflurane, respectively. Findings were confirmed by propensity score matching. Opioid dose was significantly lower in the isoflurane group (p < .001) while norepinephrine dose was significantly higher (p = .004). ConclusionIsoflurane sedation is feasible on during targeted temperature management. Time to spontaneous breathing, mechanical ventilation duration or ICU stay was not reduced by isoflurane.

Isoflurane or propofol sedation in patients with targeted temperature management after cardiopulmonary resuscitation: A retrospective single center study

Objective: Neurological prognostication for patients after cardiac arrest is challenging and often complicated by sedation during targeted temperature management. Short lasting sedatives might enable rapid awakening and early extubation. Aim of the present study was to compare sedation with intravenous propofol to volatile isoflurane.

Preconditioning renoprotective effect of isoflurane in a rat model of virtual renal transplant

BackgroundThe development of warm–cold ischemia–reperfusion (IR) injury of the kidney grafts is inevitable during renal transplantation. However, there is currently no definite renoprotective strategy available in the protection of the graft tissue. In the present study, we compared the renal protection of preconditioning isoflurane with N-acetylcysteine (NAC) in a novel rat model of warm–cold renal IR injury. Materials and methodsAdult Sprague–Dawley rats were randomly assigned to receive inhaled isoflurane (1.5% for 2 h), NAC (1 g/kg, intra-arterial injection) or placebo before the induction of brief warm ischemia (10 min) followed by cold ischemia (45 min) periods. Plasma levels of creatinine and tissue inflammatory reaction in the kidney were analyzed 72 h after reperfusion. ResultsElevated plasma level of creatinine and urea indicated the development of acute renal injury secondary to IR injury. The creatinine levels were reduced in animals pretreated with inhaled isoflurane and NAC, and the level was more significantly decreased in the isoflurane-treated group. Preconditioning with volatile isoflurane also significantly suppressed the tissue myeloperoxidase activity and expression of the inducible nitric oxide synthase. Immunostaining confirmed that myeloperoxidase expression was most significantly attenuated in the glomerulus and peritubular capillaries of rats pre-exposed to isoflurane. ConclusionsWe present the first study demonstrating that the administration of volatile isoflurane before induction of experimental warm–cold renal IR injury provides preconditioning renoprotective effect, which is superior to the treatment with NAC. The beneficial renoprotective effect of isoflurane is most likely mediated by attenuation of proinflammatory reaction in the injured kidney.

Evaluation Of Antioxidant Defense In Patients Undergoing Minor Elective Surgery With Balanced Anesthesia Maintained With The Inhaled Isoflurane

It is suggested that invasive surgical procedure can induce oxidative stress. However, only a few data regarding elective surgeries and the adjuvant effect of anesthesia are available. Fifteen patients without comorbidities, aged 18–45 years old, and scheduled for septoplasty or tympanoplasty, received general anesthesia maintained with the volatile isoflurane anesthetic. Blood samples were collected before and at the end of anesthesia. Total antioxidant performance (TAP), that measures the oxidizability of both aqueous and lipid compartments of plasma, was evaluated by fluorometry and plasma antioxidants carotenoids, tocopherols and retinol were determined by a high performance liquid chromatography (HPLC) system. Most of the carotenoids significantly decreased as well as alpha‐tocopherol and retinol (p&lt;0.001), whereas TAP was increased (p&lt;0.002) at the end of anesthesia. In vitro experiment revealed that this anesthetic showed an antioxidant potential in the equivalent concentration of blood during anesthesia in dose‐dependent manner. Thus, the current study indicates that despite of the decrease of some lipophilic endogenous antioxidants during balanced anesthesia with isoflurane in patients undergoing minor elective surgeries, the antioxidant activity of isoflurane itself may be resulted in increases of plasma TAP in these patients.Supported by FAPESP, Brazil #2010/05611–0 and USDA/USA #58–1950‐7–07

Volatile isoflurane sedation in cerebrovascular intensive care patients using AnaConDa®: effects on cerebral oxygenation, circulation, and pressure

The anesthetic-conserving device AnaConDa(®), a miniature vaporizer, allows volatile sedation in the intensive care unit (ICU). We investigated the effects of isoflurane sedation on cerebral and systemic physiology parameters in neuromonitored ICU stroke patients. Included in the study were 19 consecutive ventilated patients with intracerebral hemorrhage (12), subarachnoid hemorrhage (4), and ischemic stroke (3) who were switched from intravenous propofol or midazolam to inhalative isoflurane sedation for an average of 3.5 days. During the sedation transition, the following parameters were assessed: mean arterial pressure (MAP), intracranial pressure (ICP), cerebral perfusion pressure (CPP), middle cerebral artery mean flow velocity (MFV) and cerebral fractional tissue oxygen extraction (FTOE), as well as systemic cardiopulmonary parameters and administered drugs. After the first hour, mean ICP showed an increase of 2.1 mmHg that was not clinically relevant. Likewise, MFV did not change. MAP and CPP, however, decreased by 6.5 and 6.3 mmHg, respectively. FTOE was reduced slightly from 0.24 to 0.21 (p = 0.03). Over an observation period of 12 h, ICP remained stable, while MAP and thus CPP showed distinct decreases (CPP: -10 mmHg at 6 h, p < 0.001; -7.5 mmHg at 12 h, p = 0.005, when compared to preswitch levels) despite a 1.5-fold increase in vasopressor administration. We suggest that that it is possible to reach sufficient sedation levels in cerebrovascular ICU patients by applying volatile isoflurane long-term without a relevant increase in ICP, if baseline ICP values are low or only moderately elevated. However, caution should be exercised in view of isoflurane's decreasing effect on MAP and CPP. Multimodal neuromonitoring is strongly recommended when applying this off-label sedation method.

The preconditioning pulmonary protective effect of volatile isoflurane in acute lung injury is mediated by activation of endogenous iNOS

There is still a lack of evidence to support the use of specific anesthetic agents during major operations that could affect the development of postoperative acute lung injury (ALI). This study determined the protective effect of inhaled isoflurane in a rat model of endotoxin-induced ALI. Rats were exposed to volatile isoflurane (1.5% in oxygen) or pure oxygen via a facemask for 2h. After a 3-h recovery period, rats were reanesthetized and ALI was induced by intratracheal instillation of lipopolysaccharide (LPS, 1mg/kg in 0.5ml saline). In some animals, a specific inducible nitric oxide synthase (iNOS) inhibitor, 1400W, (10mg/kg, i.p.) was administered before exposure to isoflurane. Animals were sacrificed 12h later for analysis. Pulmonary artery vasomotor function and alveolocapillary permeability were assessed. Expression of iNOS and CD11b, and activity of myeloperoxidase in the lung were analyzed. The maximal relaxation response to acetylcholine was significantly potentiated in rats pretreated with isoflurane. Lung wet-to-dry ratio was reduced in the lung of isoflurane-treated animals. Expression of iNOS and CD11b were attenuated in the lung tissue obtained from rats receiving isoflurane. Furthermore, enzymatic activity of myeloperoxidase was also reduced in the lung preexposed to isoflurane. However, these pulmonary protective effects of isoflurane were significantly abolished by pretreatment with 1400W. Pretreatment with volatile isoflurane attenuated inflammatory process in the lung tissue of rats with LPS-induced ALI, and this preconditioning pulmonary protective effect was mainly mediated by activation of endogenous iNOS in the lung.

Reproducibility of transthoracic echocardiography in small animals using clinical equipment

Transthoracic echocardiography has been employed to assess left ventricular dimensions and function in small animals. The aim of this study was to identify the limits of transthoracic echocardiography in a commonly used Wistar rat model by assessing intraobserver variability, interobserver variability, and day-to-day variability of examinations implying registrations and measurements. Twenty male adult Wistar rats (body weight 496+/-52 g) were examined under volatile isoflurane anesthesia (heart rate 302+/-26 bpm) by transthoracic echocardiography (Sonos 7500; Philips) with a 15 MHz-transducer. For calculation of intraobserver variability, examinations were repeated by the same examiner and for interobserver variability, examinations were performed independently by two investigators. For day-to-day variability, examinations were repeated 14 days later. Left ventricular diameters and areas were analyzed in parasternal short axis and in a modified parasternal long axis. Fractional shortening, area shortening, ejection fraction, stroke volume, and cardiac output were calculated. Left ventricular end-diastolic diameter was 8.9+/-0.6 mm, fractional shortening 39.0+/-5.3%, area shortening 59.6+/-6.1%, ejection fraction 83.3+/-5.1%, stroke volume 0.24+/-0.06 ml, and cardiac output 72.9+/-20.6 ml/min. Intraobserver variability of left ventricular end-diastolic diameter, fractional shortening, area shortening, and ejection fraction was less than 10%, increasing to 19% for stroke volume and cardiac output. Interobserver variability of left ventricular end-diastolic diameter, fractional shortening, area shortening, ejection fraction was less than 13%, increasing to 23% for stroke volume and 25% for cardiac output. Day-to-day variability of left ventricular end-diastolic diameter, area shortening, ejection fraction was less than 11% whereas for stroke volume it was 21% and for cardiac output it was 22%. F-ratio test comparing investigated variabilities did not reveal significant differences. M-mode and two-dimensional echocardiography in large rats by clinically common high-end ultrasound systems can be assessed reliably. Parameters of global left ventricular performance like stroke volume and cardiac output could not be assessed with similar reliability.

The novel analgesic, F 13640, produces intra- and postoperative analgesia in a rat model of surgical pain

F 13640 is a newly discovered high-efficacy 5-HT 1A receptor agonist that produces exceptional analgesia in animal models of tonic and chronic, nociceptive and neuropathic pains by novel molecular and neuroadaptive mechanisms. Here we examined the effects of F 13640 and remifentanil (0.63 mg/kg with either compound) when injected i.p. either before or 15 min after rats underwent orthopedic surgery. Surgery consisted of the drilling of a hole in the calcaneus bone and of an incision of the skin, fascia and plantar muscle of one foot. During surgery, the concentration of volatile isoflurane was progressively incremented depending on the animal's response to surgical maneuvers. Other experiments examined the dose-dependent effects of F 13640 (0.04 to 0.63 mg/kg) on surgical pain as well as on the Minimum Alveolar Concentration of isoflurane. Both F 13640 and remifentanil markedly reduced the intra-operative isoflurane requirement. F 13640 also reduced measures of postoperative pain (i.e., paw elevation and flexion). With these postoperative measures, remifentanil produced short-lived analgesia followed by hyperalgesia. F 13640 significantly reduced both surgical pain and the isoflurane Minimum Alveolar Concentration from 0.16 mg/kg onward. F 13640 produced powerful intra- and postoperative analgesia in rats undergoing orthopedic surgery. Unlike the opioid, remifentanil, F 13640 caused no hyperalgesia with ongoing postoperative pain, and should remain effective with protracted postoperative use.