Outcomes of children with life-threatening status asthmaticus requiring isoflurane therapy and extracorporeal life support.

BACKGROUND: Severe, refractory asthma is a life-threatening emergency that may be treated with isoflurane and extracorporeal life support. The objective of this study was to describe the clinical response to isoflurane and outcomes after discharge of children who received isoflurane and/or extracorporeal life-support for near-fatal asthma. METHODS: This was a retrospective descriptive study using electronic medical record data from two pediatric intensive care units within a single healthcare system in Atlanta, GA. RESULTS: Forty-five children received isoflurane, and 14 children received extracorporeal life support, 9 without a trial of isoflurane. Hypercarbia and acidosis improved within four hours of starting isoflurane. Four children died during the index admission for asthma. Twenty-seven percent had a change in Functional Status Score of three or more points from baseline to PICU discharge. Patients had median percent predicted FEV1 and FEV1/FVC ratios pre- and post-bronchodilator values below normal pediatric values. CONCLUSION: Children who received isoflurane and/or ECLS had a high frequency of previous PICU admission and intubation. Improvement in ventilation and acidosis occurred within the first four hours of starting isoflurane. Children who required isoflurane or ECLS may develop long-lasting deficits in their functional status. Children with near-fatal asthma are a high-risk group and require improved follow-up in the year following PICU discharge.

Isoflurane promotes early spontaneous breathing in ventilated intensive care patients: A post hoc subgroup analysis of a randomized trial.

BACKGROUND: Spontaneous breathing is desirable in most ventilated patients. We therefore studied the influence of isoflurane versus propofol sedation on early spontaneous breathing in ventilated surgical intensive care patients and evaluated potential mediation by opioids and arterial carbon dioxide during the first 20 h of study sedation. METHODS: We included a single-center subgroup of 66 patients, who participated in a large multi-center trial assessing efficacy and safety of isoflurane sedation, with 33 patients each randomized to isoflurane or propofol sedation. Both sedatives were titrated to a sedation depth of -4 to -1 on the Richmond Agitation Sedation Scale. The primary outcome was the fraction of time during which patients breathed spontaneously. RESULTS: Baseline characteristics of isoflurane and propofol-sedated patients were well balanced. There were no substantive differences in management or treatment aside from sedation, and isoflurane and propofol provided nearly identical sedation depths. The mean fraction of time spent spontaneously breathing was 82% [95% CI: 69, 90] in patients sedated with isoflurane compared to 35% [95% CI: 22, 51] in those assigned to propofol: median difference: 61% [95% CI: 14, 89], p < .001. After adjustments for sufentanil dose and arterial carbon dioxide partial pressure, patients sedated with isoflurane were twice as likely to breathe spontaneously than those sedated with propofol: adjusted risk ratio: 2.2 [95%CI: 1.4, 3.3], p < .001. CONCLUSIONS: Isoflurane compared to propofol sedation promotes early spontaneous breathing in deeply sedated ventilated intensive care patients. The benefit appears to be a direct effect isoflurane rather than being mediated by opioids or arterial carbon dioxide.

Spinal cord injury-related thermoregulatory impairment masks a fatal malignant hyperthermia crisis: a case report.

PURPOSE: Malignant hyperthermia (MH) is a hypermetabolic disorder that can occur in genetically susceptible individuals exposed to halogenated anesthetics and succinylcholine. Spinal cord injury (SCI) above the sixth thoracic vertebra is associated with dysfunction of the sympathetic/parasympathetic nervous pathways, including thermoregulatory dysfunction, presenting as hypothermia in cold environments because of vasodilation and heat loss. This effect could mitigate or obscure an MH episode. Here, we describe development of a fatal MH crisis in a patient with SCI. CLINICAL FEATURES: A 27-yr-old male patient with an SCI after fracture of the sixth cervical vertebra was admitted for spinal arthrodesis. Anesthetic medications included remifentanil, propofol, succinylcholine, rocuronium, and isoflurane. After the start of the surgery, muscular contractures resembling myoclonus were noted, which resolved with pancuronium administration. Four hours after the start of anesthesia, the patient presented with hyperthermia, hypercarbia, hypotension, muscle rigidity, arrhythmia, and cardiogenic shock, with metabolic/respiratory acidosis. Malignant hyperthermia was suspected and the treatment was started, but he developed cardiopulmonary arrest and died an hour and a half after the first cardiac arrest. Both parents were investigated and were found to have normal creatine kinase levels and positive in vitro contracture tests. His mother carried a variant in the ryanodine receptor type 1 (RYR1) gene (c.14918C>T), which is associated with MH. CONCLUSION: Spinal cord injury-induced thermoregulatory dysfunction may obscure the early diagnosis of MH and lead to fatal outcome.

RéSUMé: OBJECTIF: L'hyperthermie maligne est un trouble hypermétabolique qui peut survenir chez les personnes génétiquement susceptibles exposées à des anesthésiques volatils et à la succinylcholine. Les lésions médullaires situées au-dessus de la sixième vertèbre thoracique sont associées à un dysfonctionnement des voies nerveuses sympathiques / parasympathiques, y compris un trouble de la thermorégulation, et se présentent sous forme d'hypothermie dans des environnements froids en raison de la vasodilatation et de la perte de chaleur. Cet effet pourrait atténuer ou occulter un épisode d'hyperthermie maligne. Nous décrivons ici l'apparition d'une crise mortelle d'hyperthermie maligne chez un patient atteint de lésion médullaire. CARACTéRISTIQUES CLINIQUES: Un patient de 27 ans atteint d'une lésion médullaire après une fracture de la sixième vertèbre cervicale a été admis pour une arthrodèse rachidienne. Les médicaments anesthésiques comprenaient du rémifentanil, du propofol, de la succinylcholine, du rocuronium et de l'isoflurane. Après le début de la chirurgie, des contractures musculaires ressemblant à une myoclonie ont été notées, lesquelles se sont résolues avec l'administration de pancuronium. Quatre heures après l'induction d'anesthésie, le patient a présenté une hyperthermie, une hypercarbie, une hypotension, une rigidité musculaire, une arythmie et un choc cardiogénique, avec acidose métabolique / respiratoire. Une hyperthermie maligne a été suspectée et le traitement a été amorcé, mais le patient a subi un arrêt cardiorespiratoire et est décédé une heure et demie après le premier arrêt cardiaque. Les deux parents ont passés des tests et se sont avérés avoir des taux normaux de créatine kinase et des tests de contracture in vitro positifs. La mère du patient était porteuse d'un variant du gène récepteur de ryanodine de type 1 (RYR1) (c.14918C>T), lequel est associé à l'hyperthermie maligne. CONCLUSION: Un trouble de la thermorégulation induit par une lésion médullaire peut masquer un diagnostic précoce d'hyperthermie maligne et entraîner une issue fatale.

Negative drift of sedation depth in critically ill patients receiving constant minimum alveolar concentration of isoflurane, sevoflurane, or desflurane: a randomized controlled trial.

BACKGROUND: Intensive care unit (ICU) physicians have extended the minimum alveolar concentration (MAC) to deliver and monitor long-term volatile sedation in critically ill patients. There is limited evidence of MAC's reliability in controlling sedation depth in this setting. We hypothesized that sedation depth, measured by the electroencephalography (EEG)-derived Narcotrend-Index (burst-suppression N_Index 0-awake N_Index 100), might drift downward over time despite constant MAC values. METHODS: This prospective single-centre randomized clinical study was conducted at a University Hospital Surgical Intensive Care Unit and included consecutive, postoperative ICU patients fulfilling the inclusion criteria. Patients were randomly assigned to receive uninterrupted inhalational sedation with isoflurane, sevoflurane, or desflurane. The end-expiratory concentration of the anaesthetics and the EEG-derived index were measured continuously in time-stamped pairs. Sedation depth was also monitored using Richmond-Agitation-Sedation-Scale (RASS). The paired t-test and linear models (bootstrapped or multilevel) have been employed to analyze MAC, N_Index and RASS across the three groups. RESULTS: Thirty patients were recruited (female/male: 10/20, age 64 ± 11, Simplified Acute Physiology Score II 30 ± 10). In the first 24 h, 21.208 pairs of data points (N_Index and MAC) were recorded. The median MAC of 0.58 ± 0.06 remained stable over the sedation time in all three groups. The t-test indicated in the isoflurane and sevoflurane groups a significant drop in RASS and EEG-derived N_Index in the first versus last two sedation hours. We applied a multilevel linear model on the entire longitudinal data, nested per patient, which produced the formula N_Index = 43 - 0.7·h (R2 = 0.76), showing a strong negative correlation between sedation's duration and the N_Index. Bootstrapped linear models applied for each sedation group produced: N_Index of 43-0.9, 45-0.8, and 43-0.4·h for isoflurane, sevoflurane, and desflurane, respectively. The regression coefficient for desflurane was almost half of those for isoflurane and sevoflurane, indicating a less pronounced time-effect in this group. CONCLUSIONS: Maintaining constant MAC does not guarantee stable sedation depth. Thus, the patients necessitate frequent clinical assessments or, when unfeasible, continuous EEG monitoring. The differences across different volatile anaesthetics regarding their time-dependent negative drift requires further exploration. TRIAL REGISTRATION: NCT03860129.

Molecular Aspects of Volatile Anesthetic-Induced Organ Protection and Its Potential in Kidney Transplantation.

Ischemia reperfusion injury (IRI) is inevitable in kidney transplantation and negatively impacts graft and patient outcome. Reperfusion takes place in the recipient and most of the injury following ischemia and reperfusion occurs during this reperfusion phase; therefore, the intra-operative period seems an attractive window of opportunity to modulate IRI and improve short- and potentially long-term graft outcome. Commonly used volatile anesthetics such as sevoflurane and isoflurane have been shown to interfere with many of the pathophysiological processes involved in the injurious cascade of IRI. Therefore, volatile anesthetic (VA) agents might be the preferred anesthetics used during the transplantation procedure. This review highlights the molecular and cellular protective points of engagement of VA shown in in vitro studies and in vivo animal experiments, and the potential translation of these results to the clinical setting of kidney transplantation.

Plasma histamine concentrations in horses administered sodium penicillin, guaifenesin-xylazine-ketamine and isoflurane with morphine or butorphanol.

OBJECTIVE: Various drugs administered to horses undergoing surgical procedures can release histamine. Histamine concentrations were evaluated in horses prepared for surgery and administered butorphanol or morphine intraoperative infusions. STUDY DESIGN: Prospective studies with one randomized. ANIMALS: A total of 44 client-owned horses. METHODS: In one study, anesthesia was induced with xylazine followed by ketamine-diazepam. Anesthesia was maintained with guaifenesin-xylazine-ketamine (GXK) during surgical preparation. For surgery, isoflurane was administered with intravenous (IV) morphine (group M: 0.15 mg kg-1 and 0.1 mg kg-1 hour-1; 15 horses) or butorphanol (group B: 0.05 mg kg-1 and 0.01 mg kg-1 hour-1; 15 horses). Histamine and morphine concentrations were measured using enzyme-linked immunoassay before opioid injection (time 0), and after 1, 2, 5, 30, 60 and 90 minutes. In a subsequent study, plasma histamine concentrations were measured in 14 horses before drug administration (baseline), 15 minutes after IV sodium penicillin and 15 minutes after starting GXK IV infusion. Statistical comparison was performed using anova for repeated measures. Pearson correlation compared morphine and histamine concentrations. Data are presented as mean ± standard deviation. Significance was assumed when p ≤ 0.05. RESULTS: With histamine, differences occurred between baseline (3.2 ± 2.4 ng mL-1) and GXK (5.2 ± 7.1 ng mL-1) and between baseline and time 0 in group B (11.9 ± 13.4 ng mL-1) and group M (11.1 ± 12.4 ng mL-1). No differences occurred between baseline and after penicillin or between groups M and B. Morphine concentrations were higher at 1 minute following injection (8.1 ± 5.1 ng mL-1) than at 30 minutes (4.9 ± 3.1 ng mL-1) and 60 minutes (4.0 ± 2.5 ng mL-1). Histamine correlated with morphine at 2, 30 and 60 minutes. CONCLUSIONS AND CLINICAL RELEVANCE: GXK increased histamine concentration, but concentrations were similar with morphine and butorphanol.

Repurposed molecules for antiepileptogenesis: Missing an opportunity to prevent epilepsy?

Prevention of epilepsy is a great unmet need. Acute central nervous system (CNS) insults such as traumatic brain injury (TBI), cerebrovascular accidents (CVA), and CNS infections account for 15%-20% of all epilepsy. Following TBI and CVA, there is a latency of days to years before epilepsy develops. This allows treatment to prevent or modify postinjury epilepsy. No such treatment exists. In animal models of acquired epilepsy, a number of medications in clinical use for diverse indications have been shown to have antiepileptogenic or disease-modifying effects, including medications with excellent side effect profiles. These include atorvastatin, ceftriaxone, losartan, isoflurane, N-acetylcysteine, and the antiseizure medications levetiracetam, brivaracetam, topiramate, gabapentin, pregabalin, vigabatrin, and eslicarbazepine acetate. In addition, there are preclinical antiepileptogenic data for anakinra, rapamycin, fingolimod, and erythropoietin, although these medications have potential for more serious side effects. However, except for vigabatrin, there have been almost no translation studies to prevent or modify epilepsy using these potentially "repurposable" medications. We may be missing an opportunity to develop preventive treatment for epilepsy by not evaluating these medications clinically. One reason for the lack of translation studies is that the preclinical data for most of these medications are disparate in terms of types of injury, models within different injury type, dosing, injury-treatment initiation latencies, treatment duration, and epilepsy outcome evaluation mode and duration. This makes it difficult to compare the relative strength of antiepileptogenic evidence across the molecules, and difficult to determine which drug(s) would be the best to evaluate clinically. Furthermore, most preclinical antiepileptogenic studies lack information needed for translation, such as dose-blood level relationship, brain target engagement, and dose-response, and many use treatment parameters that cannot be applied clinically, for example, treatment initiation before or at the time of injury and dosing higher than tolerated human equivalent dosing. Here, we review animal and human antiepileptogenic evidence for these medications. We highlight the gaps in our knowledge for each molecule that need to be filled in order to consider clinical translation, and we suggest a platform of preclinical antiepileptogenesis evaluation of potentially repurposable molecules or their combinations going forward.

Pharmacokinetics of vatinoxan in male neutered cats anesthetized with isoflurane.

OBJECTIVE: To characterize the pharmacokinetics of vatinoxan in isoflurane-anesthetized cats. STUDY DESIGN: Prospective experimental study. ANIMALS: A group of six adult healthy male neutered cats. METHODS: Cats were anesthetized using isoflurane in oxygen. Venous catheters were placed to administer the drug and sample blood. Vatinoxan, 1 mg kg-1, was administered intravenously over 5 minutes. Blood was sampled before and at various times during and up to 8 hours after vatinoxan administration. Plasma vatinoxan concentration was measured using liquid chromatography/tandem mass spectrometry. Compartment models were fitted to the time-concentration data using population methods and nonlinear mixed effect modeling. RESULTS: A three-compartment model best fitted the data. Typical value (% interindividual variability) for the three volumes (mL kg-1), the metabolic clearance and two distribution clearances (mL minute-1 kg-1) were 34 (55), 151 (35), 306 (18), 2.3 (34), 42.6 (25) and 5.6 (0), respectively. Hypotension increased the second distribution clearance to 10.6. CONCLUSION AND CLINICAL RELEVANCE: The pharmacokinetics of vatinoxan in anesthetized cats were characterized by a small volume of distribution and a low clearance. An intravenous bolus of 100 µg kg-1 of vatinoxan followed by constant rate infusions of 55 µg kg-1 minute-1 for 20 minutes, then 22 µg kg-1 minute-1 for 60 minutes and finally 10 µg kg-1 minute-1 for the remainder of the infusion time is expected to maintain the plasma concentration within 90%-110% of the plasma vatinoxan concentration previously shown to attenuate the cardiovascular effects of dexmedetomidine (25 µg kg-1) in conscious cats.

Anaesthetic management for hiatal hernia repair in a child with Bartter's syndrome: A case report.

Bartter syndrome is a rare disorder characterized by reduced sodium chloride transport in the distal nephrons of the kidney. Its clinical features are renal salt wasting, hypokalemic metabolic alkalosis, elevated renin and aldosterone levels with normal or low blood pressure, polyuria, hypercalciuria and malnutrition. The pathophysiologic and biochemical changes in these patients should be kept in mind when considering anaesthetic management. This case report describes our management in a nineteen months old, 3.6 kg weight male child with Bartter's syndrome who underwent elective repair of hiatal hernia and gastrostomy.

TGF-ß2/Smad3 Signaling Pathway Activation Through Enhancing VEGF and CD34 Ameliorates Cerebral Ischemia/Reperfusion Injury After Isoflurane Post-conditioning in Rats.

Evidence has shown the therapeutic potential of isoflurane (ISO) in cerebral stroke. The present study investigated the mechanism of ISO on vascular endothelial growth factor (VEGF) and CD34 expression in a rat model of stroke. Transient focal cerebral ischemia was established by middle cerebral artery occlusion (MCAO) for 1 h followed by reperfusion for 24 h in rats. ISO was administered for 1.5 h when the reperfusion was initiated. Neurologic deficit scores, infarct volumes, HE staining, Nissl staining, and TUNEL staining were evaluated at 24 h after reperfusion. The levels of transforming growth factor (TGF)-ß2, Smad3, p-Smad3, VEGF, and CD34 proteins were detected by immunofluorescence (IF) staining and Western blot assay. Administration of ISO significantly reduced the neurologic deficit scores, infarct volumes, and damaged and apoptotic cells after cerebral ischemia/reperfusion (I/R) injury (P < 0.05). Meanwhile, ISO post-conditioning significantly increased the expression levels of TGF-ß2, p-Smad3, VEGF, and CD34 (P < 0.05), whereas the expression of Smad3 showed no difference (P > 0.05). However, Pirfenidone, a TGF-ß2 inhibitor, decreased the expression levels of TGF-ß2, p-Smad3, VEGF, and CD34 (P < 0.05). Moreover, the protective effects of ISO post-conditioning were negated by the inhibitor. The present study indicated that ISO attenuates brain damage by activating the TGF-ß2/Smad3 signaling pathway and increasing the protein expression of VEGF and CD34 in the rat MCAO model.

The depth of anaesthesia associated with the administration of isoflurane 2.5% during cardiopulmonary bypass.

BACKGROUND: Administering isoflurane 2.5% into the oxygenator during cardiopulmonary bypass results in no patient movement. However, doing so may result in an excessive depth of anaesthesia particularly, when hypothermia is induced. Bispectral index and arterial blood and oxygenator exhaust concentrations of volatile anaesthetics should be related to depth of anaesthesia. The primary aim of this study was to measure the depth of anaesthesia using bispectral index, resulting from administering isoflurane 2.5% into the oxygenator during cardiopulmonary bypass, and secondary aims were to examine the relationships between blood and oxygenator exhaust isoflurane concentrations and bispectral index. METHODS: Arterial and mixed-venous blood samples were aspirated at three time points during cardiopulmonary bypass and measured for isoflurane concentration using mass spectrometry. Simultaneously, oxygenator exhaust isoflurane concentration, nasopharyngeal temperature and bispectral index were recorded. RESULTS: When averaged across the three time points, all patients had a bispectral index score below 40 (binomial test, p < 0.001). There were no significant correlations between bispectral index score and arterial or mixed-venous blood isoflurane concentrations (r = -0.082, p = 0.715; r = -0.036, p = 0.874) and oxygenator exhaust gas concentration of isoflurane (r = -0.369, p = 0.091). CONCLUSION: When 2.5% isoflurane was administered into the sweep gas supply to the oxygenator during cardiopulmonary bypass, all patients experienced a bispectral index score less than 40 and no significant relationship was found between either arterial or mixed-venous blood or oxygenator exhaust concentrations of isoflurane and bispectral index.

Fetal Surgery Decreases Anesthesia-Induced Neuroapoptosis in the Mid-Gestational Fetal Ovine Brain.

BACKGROUND: Studies demonstrating an association between anesthesia and brain cell death (neuroapoptosis) in young animals were performed without accompanying surgery. This study tests the hypothesis that fetal surgery decreases anesthesia-induced neuroapoptosis. MATERIALS AND METHODS: Seventy-day-pregnant ewes received 2% isoflurane for 1 h (low dose [LD]) or 4% for 3 h (high dose [HD]) with or without fetal surgery (S). Unexposed fetuses served as controls (C). Fetal brains were processed for neuroapoptosis using anti-caspase-3 antibodies. Data were analyzed using ANOVA. RESULTS: Twenty-eight fetal sheep were evaluated. Dentate gyrus neuroapoptosis was lower in the HD+S group (13.1 ± 3.76 × 105/mm3) than in the HD (19.1 ± 1.40 × 105/mm3, p = 0.012) and C groups (18.3 ± 3.55 × 105/mm3, p = 0.035). In the pyramidal layer of the hippocampus, neuroapoptosis was lower in the HD+S group (8.11 ± 4.88 × 105/mm3) than in the HD (14.8 ± 2.82 × 105/mm3, p = 0.006) and C groups (14.1 ± 4.54 × 105/mm3, p = 0.019). The LD+S group showed a trend towards a significant decrease in neuroapoptosis in the pyramidal layer (LD+S 7.51 ± 1.48 vs. LD 13.5 ± 1.87 vs. C 14.1 ± 4.54 × 105/mm3, p = 0.07) but not in the dentate gyrus. Fetal surgery did not affect neuroapoptosis in the frontal cortex or endplate. CONCLUSIONS: Fetal surgery decreases isoflurane-induced neuroapoptosis in the dentate gyrus and the pyramidal layer of mid-gestational fetal sheep. Long-term effects of these observations on memory and learning deserve further exploration.

Isoflurane alone versus small dose propofol with isoflurane for removal of laryngeal mask airway in children-a randomized controlled trial.

OBJECTIVE: To compare the safety of laryngeal mask airway removal using two different deep anaesthesia techniques in paediatric patients. METHODS: The Randomized Control Trial was conducted at Aga Khan University Hospital, Karachi, from April 2012 to November 2013, and comprised patients aged 2-10 years scheduled for infraumbilical surgeries. Anaesthesia was induced with sevoflurane and later it was maintained by is oflurane, oxygen and nitrous oxide. The laryngeal mask airway was removed in the intervention group-I at 0.4 minimum alveolar concentration of isoflurane with propofol 1mg/kg. In the control group-II, it was removed at 1.2 minimum alveolar concentration of isoflurane alone. SPSS 19 was used for data analysis. RESULTS: Of the 50 patients, there were 25(50%) in each of the two groups. Overall, there were 46(92%) males and 4(8%) females. Incidence of airway obstruction and teeth clenching was significantly higher in group-II (p<0.05 each). Emergence duration was also significantly increased in group-II compared to group-I (p=0.001). The Post-Anaesthesia Care Unit stay timing was not significantly different between the groups (p=0.74). CONCLUSIONS: Laryngeal mask airway removal under deep anaesthetic technique of low-dose propofol with isoflurane was found to be associated with minimal adverse airway events than isoflurane alone in paediatric patients.

Propofol Attenuates the Myocardial Protection Properties of Desflurane by Modulating Mitochondrial Permeability Transition.

BACKGROUND: Desflurane and propofol are cardioprotective, but relative efficacy is unclear. The aim was to compare myocardial protection of single, simultaneous, and serial administration of desflurane and propofol. METHODS: Sixty New Zealand White rabbits and 65 isolated Sprague Dawley rat hearts randomly received desflurane, propofol, simultaneous desflurane and propofol, or sequential desflurane then propofol. Rabbits were subdivided to receive either ischemia-reperfusion with temporary occlusion of the left anterior descending artery or a time-matched, nonischemic perfusion protocol, whereas rat hearts were perfused in a Langendorff model with global ischemia-reperfusion. End points were hemodynamic, functional recovery, and mitochondrial uptake of H-2-deoxy-D-glucose as an indicator of mitochondrial permeability transition. RESULTS: In rabbits, there were minimal increases in preload-recruitable stroke-work with propofol (P < .001), desflurane (P < .001), and desflurane-and-propofol (P < .001) groups, but no evidence of increases with pentobarbitone (P = .576) and desflurane-then-propofol (P = .374). In terms of end-diastolic pressure-volume relationship, there was no evidence of increase compared to nonischemic controls with desflurane-then-propofol (P = .364), a small but significant increase with desflurane (P < .001), and larger increases with pentobarbitone (P < .001), propofol (P < .001), and desflurane-and-propofol (P < .001).In rat hearts, there was no statistically significant difference in mitochondrial H-activity between propofol and desflurane-and-propofol (165 ± 51 × 10 vs 154 ± 51 × 10 g·mL·min/µmol; P = .998). Desflurane had lower uptake than propofol (65 ± 21 × 10 vs 165 ± 51 × 10 g·mL·min/µmol; P = .039), but there was no statistically significant difference between desflurane and desflurane-then-propofol (65 ± 21 × 10 vs 59 ± 11 × 10 g·mL·min/µmol; P = .999). CONCLUSIONS: Propofol and desflurane are cardioprotective, but desflurane is more effective than propofol. The added benefit of desflurane is lost when used simultaneously with propofol.

Assessing the depth of isoflurane anaesthesia during cardiopulmonary bypass.

INTRODUCTION: Bispectral index (BIS) and monitoring of end-tidal concentration may be associated with a reduction in the incidence of awareness during volatile-based general anaesthesia. An analogue of end-tidal concentration during cardiopulmonary bypass (CPB) is measuring exhausted isoflurane concentration from the oxygenator as an estimate to blood and, so, brain concentration. The aim of this study was to determine the relationships between oxygenator exhaust and blood concentrations of isoflurane and the BIS score during CPB when administering isoflurane into the sweep gas supply to the oxygenator. METHODS: Seventeen patients undergoing elective cardiac surgery using CPB and isoflurane with BIS monitoring were recruited in a single-centre university hospital. Isoflurane gas was delivered via a calibrated vaporiser at the beginning of anaesthetic induction. Radial arterial blood samples were collected after the initiation of CPB and before aortic cross-clamping, which were analysed for isoflurane by gas chromatography and mass spectrometry. The BIS score and the concentration of exhausted isoflurane from the oxygenator membrane, as measured by an anaesthetic gas analyser, were recorded at the time of blood sampling. RESULTS: The mean duration of anaesthetic induction to arterial blood sampling was 90 min (95%CI: 80,100). On CPB, the median BIS was 39 (range, 7-43) and the mean oxygenator exhaust isoflurane concentration was 1.24 ± 0.21%. No significant correlation was demonstrated between BIS with arterial isoflurane concentration (r=-0.19, p=0.47) or oxygenator exhaust isoflurane concentration (r=0.07, p=0.80). Mixed-venous blood temperature was moderately correlated to BIS (r=0.50, p=0.04). Oxygenator exhaust isoflurane concentration was moderately, positively correlated with its arterial concentration (r=0.64, p<0.01). DISCUSSION: In conclusion, in patients undergoing heart surgery with CPB, the findings of this study indicate that, whilst oxygenator exhaust concentrations were significantly associated with arterial concentrations of isoflurane, neither had any association with the BIS scores, whereas body temperature has moderate positive correlation.

Emerging evidence for antidepressant actions of anesthetic agents.

PURPOSE OF REVIEW: After decades without substantial advances, multiple novel antidepressants show promise against treatment-resistant depression. Interestingly, many of these are anesthetics. The purpose of this review is to discuss the evidence for the antidepressant effects of ketamine, nitrous oxide, isoflurane and propofol and to consider potential clinical, administrative and research implications for anesthesiologists. RECENT FINDINGS: Ketamine has acute, transient antidepressant and antisuicidal effects. Nitrous oxide has also shown antidepressant efficacy. There are converging preclinical and clinical data that isoflurane (and perhaps propofol), dosed to burst suppression, has relatively rapid, robust and durable antidepressant effects and lacks the adverse effects associated with electroconvulsive therapy (ECT). SUMMARY: Several anesthetics show promise as novel antidepressants. Ketamine is the most well studied. Anesthetic-induced burst-suppression may provide an alternative to ECT that lacks adverse cognitive effects. Further study is necessary to better understand how these drugs work and how they might be used as effective antidepressant therapy.

Optimization of analgesia for piglet castration under isoflurane anaesthesia with parenteral butorphanol, meloxicam or intratesticular lidocaine.

INTRODUCTION: This blinded prospective study investigated analgesic effects of intramuscular (IM) butorphanol, meloxicam or intratesticular (IT) lidocaine for castration of 7-14 days old piglets under isoflurane anaesthesia. 66 piglets were randomly injected with: meloxicam IM (0.4 mg/kg; group M), butorphanol IM (0.2 mg/kg; group B), or both (group BM) 20 minutes prior to castration, or lidocaine IT (4 mg/kg (group ML4) or 8 mg/kg (group ML8)) together with meloxicam IM (0.4 mg/kg) under anaesthesia with 1.8% end-tidal isoflurane. Heart rate, respiratory rate, mean arterial blood pressure and end-tidal carbon dioxide were recorded. Anaesthesia quality was scored and postoperative behaviour assessed. As butorphanol caused unacceptable side effects, its use was stopped. Group M showed worse anaesthesia quality than ML4 and ML8 (higher incidence of movements: 11/17, 3/18 and 4/17, respectively). There were no significant differences between groups regarding parameters measured during castration. Postoperative behaviour did not differ between groups. For castration of 7-14 days old piglets under isoflurane anaesthesia, IT lidocaine provides an additional side effect free analgesia.

INTRODUCTION: Cette étude prospective en aveugle étudie l'effet analgésique de l'injection intramusculaire (IM) de butorphanol et de méloxicam ou de l'injection intra-testiculaire (IT) de lidocaïne pour la castration, sous anesthésie à l'isoflurane, de porcelets âgés de 7 à 14 jours. Soixante-six porcelets ont reçu de manière aléatoire soit du méloxicam IM (0.4 mg/kg; groupe M), soit du butorphanol IM (0.2 mg/kg; groupe B), soit les deux substances (groupe MB) 20 minutes avant la castration, soit de la lidocaïne IT (4 mg/kg (groupe ML4) ou 8 mg/kg (groupe ML8)) ainsi que du méloxicam IM (0.4 mg/kg), avec une anesthésie à l'isoflurane à 1.8% en fin d'expiration. Les fréquences cardiaques et respiratoires, la pression artérielle moyenne et le CO2 en fin d'expiration ont été documentés. La qualité de l'anesthésie a été estimée et le comportement post-opératoire observé. Le butorphanol a causé des effets secondaires inacceptables et son usage a été stoppé. Le groupe M montrait une plus mauvaise qualité d'anesthésie que les groupes ML4 et ML8 (plus grande incidence de mouvements : 11/17, 3/18 et 4/17). Les autres paramètres intra opératoires ne présentaient pas de différences significatives et on a pas constaté de différences entre les groupes dans la phase postopératoire. Pour la castrations de porcelets âgés de 7 à 14 jours sous anesthésie à l'isoflurane, l'utilisation intra testiculaire de lidocaïne représente une analgésie supplémentaire dépourvue d'effets secondaires.

ANESTHESIA OF AQUARIUM-HOUSED WALRUS ( ODOBENUS ROSMARUS): A CASE SERIES.

Walruses are a challenging species to anesthetize as a result of their large mass, limited access for drug delivery, unique physiology, and small number of reports describing anesthetic procedures. Three aquarium-housed walruses ( Odobenus rosmarus) ranging in age from 3 to 11 yr old (344-1,000 kg) were anesthetized for dental or ophthalmic surgical procedures, with one animal anesthetized twice and one anesthetized three times. Preanesthetic medication was with intramuscular midazolam (0.1-0.2 mg/kg) and meperidine (2-3 mg/kg). A catheter was placed in the extradural intravertebral vein, and anesthesia was induced with propofol to effect. Orotracheal intubation was performed and anesthesia maintained with isoflurane in oxygen using a circle breathing system connected to a ventilator. Intermittent positive pressure ventilation was used in all procedures. For the ophthalmic surgery, the neuromuscular blocking agent, cisatracurium, was given intravenously to provide a central eye and optimal surgical conditions. The neuromuscular block was antagonized with edrophonium. Total anesthesia times ranged from 1.5 to 6 hr. Midazolam and meperidine were antagonized with flumazenil and naltrexone, respectively, in five of six cases. Nonsteroidal anti-inflammatory agents were provided for analgesia. Recoveries were calm and uneventful. The described anesthetic protocols and case management were successful under the conditions encountered.

Isoflurane Sedation on the ICU in Cardiac Arrest Patients Treated With Targeted Temperature Management: An Observational Propensity-Matched Study.

OBJECTIVE: Targeted temperature management after cardiac arrest requires deep sedation to prevent shivering and discomfort. Compared to IV sedation, volatile sedation has a shorter half-life and thus may allow more rapid extubation and neurologic assessment. DESIGN: Observational analysis of clinical data. SETTING: University hospital, medical ICU. PATIENTS: Four hundred thirty-two cardiac arrest survivors underwent targeted temperature management; of those, 110 were treated with volatile sedation using an anesthetic conserving device and isoflurane, and 322 received standard IV sedation. INTERVENTION: No intervention. MEASUREMENT AND MAIN RESULTS: A matched pairs analysis revealed that time on ventilator (difference of median, 98.5 hr; p = 0.003) and length of ICU stay (difference of median, 4.5 d; p = 0.006) were significantly shorter in patients sedated with isoflurane when compared with IV sedation although no differences in neurologic outcome (45% of patients with cerebral performance category 1-2 in both groups) were observed. Significant hypercapnia occurred more frequently during anesthetic conserving device use (6.4% vs 0%; p = 0.021). CONCLUSIONS: Volatile sedation is feasible in cardiac arrest survivors. Prospective controlled studies are necessary to confirm the beneficial effects on duration of ventilation and length of ICU stay observed in our study. Our data argue against a major effect on neurologic outcome. Close monitoring of PaCO2 is necessary during sedation via anesthetic conserving device.

Critical role of P2X7 receptors in the neuroinflammation and cognitive dysfunction after surgery.

Postoperative cognitive dysfunction worsens patient outcome after surgery. Neuroinflammation is a critical neuropathological process for it. We determined the role of P2X7 receptors, proteins that participate in inflammatory response, in the neuroinflammation induction after surgery, and whether the choice of volatile anesthetics affects its occurrence. Eight-week old C57BL/6J or P2X7 receptor knockout male mice were subjected to right carotid arterial exposure under anesthesia with 1.8% isoflurane, 2.5% sevoflurane or 10% desflurane. They were tested by Barnes maze and fear conditioning from 2weeks after the surgery. Hippocampus was harvested 6h, 24h and 7days after the surgery for immunohistochemical staining and Western blotting. Mice with surgery under anesthesia with isoflurane, sevoflurane or desflurane took longer than control mice to identify the target box 1 or 8days after the training sessions in Barnes maze. Mice anesthetized by isoflurane or sevoflurane, but not by desflurane, had less freezing behavior than control mice in fear conditioning test. Mice with surgery and anesthesia had increased ionized calcium binding adapter molecule 1 and interleukin 1ß in the hippocampus but this increase was smaller in mice anesthetized with desflurane than mice anesthetized with isoflurane. Mice with surgery had increased P2X7 receptors and its downstream molecule caspase 1. Inhibition or knockout of P2X7 receptors attenuated surgery and anesthesia-induced neuroinflammation and cognitive impairment. We conclude that surgery under desflurane anesthesia may have reduced neuroinflammation and cognitive impairment compared with surgery under isoflurane anesthesia. P2X7 receptors may mediate the neuroinflammation and cognitive impairment after surgery.