ACE-Inhibitor or ARB-Induced Refractory Hypotension Treated With Vasopressin in Patients Undergoing General Anesthesia for Dentistry: Two Case Reports.

Two case reports present the use of vasopressin for treating refractory hypotension associated with continued angiotensin-converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB) therapy prior to general anesthesia for oral surgery. Both patients were treated in an ambulatory dental surgery clinic and took either their ACEI or ARB medication for hypertension within 24 hours prior to undergoing an intubated general anesthetic. Persistent profound hypotension was encountered intraoperatively that was refractory to treatment with traditional methods. However, the ACEI- or ARB-induced refractory hypotension was successfully managed with the administration of vasopressin.

Long-term cognitive and behavioral outcomes following early exposure to general anesthetics.

PURPOSE OF REVIEW: Nearly 100 clinical studies have been published evaluating neurodevelopmental outcomes in children following surgery and anesthesia. These studies have reported mixed results, likely attributable at least in part to significant heterogeneity in their study designs, types and numbers of exposures, patient populations evaluated, and most importantly, the outcomes that were assessed. This review aims to summarize the results from clinical studies evaluating behavioral outcomes in children exposed to surgery and anesthesia. RECENT FINDINGS: Children with early exposure to surgery and anesthesia were found to have limited to no differences in intelligence when compared with unexposed children. However, several studies have reported more behavioral problems in children exposed to general anesthesia. An increased incidence of attention-deficit hyperactivity disorder has also been reported in anesthetic exposed children, particularly after multiple exposures. SUMMARY: Nearly all clinical studies of anesthetic neurotoxicity are observational in nature, so the associations between anesthetic exposure and behavioral deficits cannot yet be directly attributed to the anesthetic medication. However, the finding of deficits in some neurodevelopmental domains and not others will help guide the selection of appropriate outcomes in future studies of anesthetic neurotoxicity that can further evaluate whether anesthetic medications have an impact on neurodevelopment in children.

Prevalence of postoperative delirium with different combinations of intraoperative general anesthetic agents in patients undergoing cardiac surgery: A retrospective propensity-score-matched study.

ABSTRACT: Postoperative delirium (PD) remains an issue in cardiac surgery despite the constant efforts to reduce its incidence. In this retrospective study, the incidence of PD was evaluated in patients who underwent cardiac surgery with cardiopulmonary bypass (CPB) according to different primary anesthetic agents: sevoflurane and dexmedetomidine- versus propofol-based anesthesia.A total of 534 patients who underwent heart-valve surgery or coronary artery bypass graft surgery with CPB between January 2012 and August 2017 were divided into 2 groups according to the main anesthetic agent: sevoflurane with dexmedetomidine (sevo-dex group, n = 340) and propofol (propofol group, n = 194). The incidence of PD was evaluated as the primary outcome. Patient-, surgery-, and anesthesia-related factors and postoperative complications were investigated as secondary outcomes. To reduce the risk of confounding effects between the 2 groups, 194 patients were selected from the sevo-dex group after propensity-score matching.After propensity-score matching, the incidence of PD was not significantly different between the sevo-dex (6.2%) and propofol (10.8%) groups (P = .136). In comparisons of the incidence of each type of PD, only hyperactive PD occurred significantly less frequently in the sevo-dex group (P = .021). Older age, lower preoperative albumin levels, and emergency surgery were significant risk factors for PD.The overall incidence of PD after cardiac surgery with CPB did not differ between patients receiving sevoflurane and dexmedetomidine-based versus propofol-based anesthesia. Only hyperactive PD occurred less frequently in patients receiving sevoflurane and dexmedetomidine-based anesthesia.

Dendritic spine remodeling and plasticity under general anesthesia.

Ever since its first use in surgery, general anesthesia has been regarded as a medical miracle enabling countless life-saving diagnostic and therapeutic interventions without pain sensation and traumatic memories. Despite several decades of research, there is a lack of understanding of how general anesthetics induce a reversible coma-like state. Emerging evidence suggests that even brief exposure to general anesthesia may have a lasting impact on mature and especially developing brains. Commonly used anesthetics have been shown to destabilize dendritic spines and induce an enhanced plasticity state, with effects on cognition, motor functions, mood, and social behavior. Herein, we review the effects of the most widely used general anesthetics on dendritic spine dynamics and discuss functional and molecular correlates with action mechanisms. We consider the impact of neurodevelopment, anatomical location of neurons, and their neurochemical profile on neuroplasticity induction, and review the putative signaling pathways. It emerges that in addition to possible adverse effects, the stimulation of synaptic remodeling with the formation of new connections by general anesthetics may present tremendous opportunities for translational research and neurorehabilitation.

Effects of general anaesthesia during pregnancy on neurocognitive development of the fetus: a systematic review and meta-analysis.

BACKGROUND: The US Food and Drug Administration warned that exposure of pregnant women to general anaesthetics may impair fetal brain development. This review systematically evaluates the evidence underlying this warning. METHODS: PubMed, EMBASE, and Web of Science were searched from inception until April 3, 2020. Preclinical and clinical studies were eligible. Exclusion criteria included case reports, in vitro models, chronic exposures, and exposure only during delivery. Meta-analyses were performed on standardised mean differences. The primary outcome was overall effect on learning/memory. Secondary outcomes included markers of neuronal injury (apoptosis, synapse formation, neurone density, and proliferation) and subgroup analyses. RESULTS: There were 65 preclinical studies included, whereas no clinical studies could be identified. Anaesthesia during pregnancy impaired learning and memory (standardised mean difference -1.16, 95% confidence interval -1.46 to -0.85) and resulted in neuronal injury in all experimental models, irrespective of the anaesthetic drugs and timing in pregnancy. Risk of bias was high in most studies. Rodents were the most frequently used animal species, although their brain development differs significantly from that in humans. In a minority of studies, anaesthesia was combined with surgery. Monitoring and strict control of physiological homeostasis were below preclinical and clinical standards in many studies. The duration and frequency of exposure and anaesthetic doses were often much higher than in clinical routine. CONCLUSION: Anaesthesia-induced neurotoxicity during pregnancy is a consistent finding in preclinical studies, but translation of these results to the clinical situation is limited by several factors. Clinical observational studies are needed. PROSPERO REGISTRATION NUMBER: CRD42018115194.

A synthetic peptide rescues rat cortical neurons from anesthetic-induced cell death, perturbation of growth and synaptic assembly.

Anesthetics are deemed necessary for all major surgical procedures. However, they have also been found to exert neurotoxic effects when tested on various experimental models, but the underlying mechanisms remain unknown. Earlier studies have implicated mitochondrial fragmentation as a potential target of anesthetic-induced toxicity, although clinical strategies to protect their structure and function remain sparse. Here, we sought to determine if preserving mitochondrial networks with a non-toxic, short-life synthetic peptide-P110, would protect cortical neurons against both inhalational and intravenous anesthetic-induced neurotoxicity. This study provides the first direct and comparative account of three key anesthetics (desflurane, propofol, and ketamine) when used under identical conditions, and demonstrates their impact on neonatal, rat cortical neuronal viability, neurite outgrowth and synaptic assembly. Furthermore, we discovered that inhibiting Fis1-mediated mitochondrial fission reverses anesthetic-induced aberrations in an agent-specific manner. This study underscores the importance of designing mitigation strategies invoking mitochondria-mediated protection from anesthetic-induced toxicity in both animals and humans.

Prenatal Exposure to General Anesthesia and Childhood Behavioral Deficit.

BACKGROUND: Exposure to surgery and anesthesia in early childhood has been found to be associated with an increased risk of behavioral deficits. While the US Food and Drug Administration (FDA) has warned against prenatal exposure to anesthetic drugs, little clinical evidence exists to support this recommendation. This study evaluates the association between prenatal exposure to general anesthesia due to maternal procedures during pregnancy and neuropsychological and behavioral outcome scores at age 10. METHODS: This is an observational cohort study of children born in Perth, Western Australia, with 2 generations of participants contributing data to the Raine Study. In the Raine Study, the first generation (Gen1) are mothers enrolled during pregnancy, and the second generation (Gen2) are the children born to these mothers from 1989 to 1992 with neuropsychological and behavioral tests at age 10 (n=2024). In the primary analysis, 6 neuropsychological and behavioral tests were evaluated at age 10: Raven's Colored Progressive Matrices (CPM), McCarron Assessment of Neuromuscular Development (MAND), Peabody Picture Vocabulary Test (PPVT), Symbol Digit Modality Test (SDMT) with written and oral scores, Clinical Evaluation of Language Fundamentals (CELF) with Expressive, Receptive, and Total language scores, and Child Behavior Checklist (CBCL) with Internalizing, Externalizing, and Total behavior scores. Outcome scores of children prenatally exposed to general anesthesia were compared to children without prenatal exposure using multivariable linear regression models adjusting for demographic and clinical covariates (sex, race, income, and maternal education, alcohol or tobacco use, and clinical diagnoses: diabetes, epilepsy, hypertension, psychiatric disorders, or thyroid dysfunction). Bonferroni adjustment was used for the 6 independent tests in the primary analysis, so a corrected P value <.0083 (P = .05 divided by 6 tests, or a 99.17% confidence interval [CI]) was required for statistical significance. RESULTS: Among 2024 children with available outcome scores, 22 (1.1%) were prenatally exposed to general anesthesia. Prenatally exposed children had higher CBCL Externalizing behavioral scores (score difference of 6.1 [99.17% CI, 0.2-12.0]; P = .006) than unexposed children. Of 6 tests including 11 scores and subscores, only CBCL Externalizing behavioral scores remained significant after multiple comparisons adjustment with no significant differences found in any other score. CONCLUSIONS: Prenatal exposure to general anesthetics is associated with increased externalizing behavioral problems in childhood. However, given the limitations of this study and that avoiding necessary surgery during pregnancy can have significant detrimental effects on the mother and the child, further studies are needed before changes to clinical practice are made.

Adult Emergence Agitation: A Veteran-Focused Narrative Review.

Emergence agitation (EA) is a self-limited state of psychomotor excitement during awakening from general anesthesia. EA is confined to the emergence period as consciousness is restored, which sharply distinguishes it from other postoperative delirium states. Sporadic episodes of EA may become violent with the potential for harm to both patients and caregivers, but the long-term consequences of such events are not fully understood. Current literature on EA in adults is limited to small-scale studies with inconsistent nomenclature, variable time periods that define emergence, a host of different surgical populations, and conflicting diagnostic criteria. Therefore, true incidence rates and risk factors are unknown. In adult noncardiac surgery, the incidence of EA is approximately 19%. Limited data suggest that young adults undergoing otolaryngology operations with volatile anesthetic maintenance may be at the highest risk for EA. Currently suggested EA mechanisms are theoretical but might reflect underblunted sympathetic activation in response to various internal (eg, flashbacks or anxiety) or external (eg, surgical pain) stimuli as consciousness returns. Supplemental dexmedetomidine and ketamine may be utilized for EA prevention. Compared to the civilian population, military veterans may be more vulnerable to EA due to high rates of posttraumatic stress disorder (PTSD) manifesting as violent flashbacks; however, confirmatory data are limited. Nonetheless, expert military medical providers suggest that use of patient-centered rapport tactics, PTSD trigger identification and avoidance, and grounding measures may alleviate hyperactive emergence phenomena. Future research is needed to better characterize EA in veterans and validate prophylactic measures to optimize care for these patients. This narrative review provides readers with an important framework to distinguish EA from delirium. Furthermore, we summarize current knowledge of EA risk factors, mechanisms, and adult management strategies and specifically revisit them in the context of veteran perioperative health. The anesthesiology care team is ideally positioned to further explore EA and develop effective prevention and treatment protocols.

Association between surgical procedures under general anesthesia in infancy and developmental outcomes at 1 year: the Japan Environment and Children's Study.

BACKGROUND: The neurotoxicity of general anesthesia to the developing human brains is controversial. We assessed the associations between surgery under general anesthesia in infancy and development at age 1 year using the Japan Environment and Children's Study (JECS), a large-scale birth cohort study. METHODS: In the JECS, 103,062 pregnancies and 104,065 fetuses were enrolled between January 2011 and March 2014. Of the 100,144 registered live births, we excluded preterm or post-term infants, multiple births, and infants with chromosomal anomalies and/or anomalies of the head or brain. Data on surgical procedures under general anesthesia in infancy were collected from self-administered questionnaires by parents at the 1-year follow-up. Developmental delay at age 1 year was assessed using the Japanese translation of the Ages and Stages Questionnaires, Third Edition (J-ASQ-3), comprising five developmental domains. RESULTS: Among the 64,141 infants included, 746 infants had surgery under general anesthesia once, 90 twice, and 71 three or more times. The percentage of developmental delay in the five domains of the J-ASQ-3 significantly increased with the number of surgical procedures. After adjusting for potential confounding factors, the risk of developmental delays in all five domains was significantly increased in infants who had surgery under general anesthesia three times or more (adjusted odds ratios: for communication domain 3.32; gross motor domain 4.69; fine motor domain 2.99; problem solving domain 2.47; personal-social domain 2.55). CONCLUSIONS: Surgery under general anesthesia in infancy was associated with an increased likelihood of developmental delay in all five domains of the J-ASQ-3, especially the gross motor domain at age 1 year. The neurodevelopment with the growth should be further evaluated among the children who had surgery under general anesthesia. TRIAL REGISTRATION: UMIN Clinical Trials Registry (number: UMIN000030786 ).

Surgical Field Visualization during Functional Endoscopic Sinus Surgery: Comparison of Propofol- vs Desflurane-Based Anesthesia.

OBJECTIVE: To assess if the type of general anesthetic affects bleeding and field visualization during endoscopic sinus surgery. STUDY DESIGN: Prospective, randomized, controlled trial. SETTING: Academic teaching hospital and Veterans Affairs hospital in the United States. SUBJECTS AND METHODS: Seventy patients were randomized to 1 of 3 anesthetic regimens: (1) the volatile anesthetic desflurane (n = 22), (2) intravenous anesthesia with propofol (n = 25), or (3) a combination of propofol and desflurane (n = 23). Intravenous remifentanil was titrated to decrease the mean arterial pressure to 60 to 70 mm Hg but not ≥30% from baseline. Surgical bleeding scores were recorded along with bleeding rates and hemodynamic parameters, including cardiac output and systemic vascular resistance through pulse contour analysis from a radial arterial line. Statistics: multiple comparison tests and regression analyses; α = .05. RESULTS: There were no differences in bleeding rate (median, 0.58, 0.85, 0.57 mL min-1), bleeding score (2.1, 2.0, 2.0), surgery duration (79, 81, 86 minutes), extubation time (9, 7, 8 minutes), recovery room time (65, 61, 61 minutes), or any hemodynamic parameters among groups 1 through 3, respectively. Group 1 required lower remifentanil infusions than group 2 (0.11 vs 0.26 µg kg-1 min-1; P = .01). The bleeding score correlated positively with height (P = .014) and the Lund-MacKay score (P = .013). Bilateral vs unilateral surgery led to longer surgery duration (P = .001) and recovery room time (P = .004). CONCLUSION: When remifentanil is used for controlled hypotension, propofol has no advantage over desflurane to improve surgical field visualization during functional endoscopic sinus surgery.

Automated Pulse Oximeter Waveform Analysis to Track Changes in Blood Pressure During Anesthesia Induction: A Proof-of-Concept Study.

BACKGROUND: Intraoperative hypotension is associated with postoperative complications and death. Oscillometric brachial cuffs are used to measure arterial pressure (AP) in most surgical patients but may miss acute changes in AP. We hypothesized that pulse oximeter waveform analysis may help to detect changes in systolic AP (SAP) and mean AP (MAP) during anesthesia induction. METHODS: In 40 patients scheduled for an elective surgery necessitating general anesthesia and invasive AP monitoring, we assessed the performance of a pulse oximeter waveform analysis algorithm (optical blood pressure monitoring [oBPM]) to estimate SAP, MAP, and their changes during the induction of general anesthesia. Acute AP changes (>20%) in SAP and MAP assessed by the reference invasive method and by oBPM were compared using 4-quadrant and polar plots. The tracking ability of the algorithm was evaluated on changes occurring over increasingly larger time spans, from 30 seconds up to 5 minutes. The second objective of the study was to assess the ability of the oBPM algorithm to cope with the Association for the Advancement of Medical Instrumentation (AAMI) standards. The accuracy and precision of oBPM in estimating absolute SAP and MAP values compared to the invasive method was evaluated at various instants after algorithm calibration, from 30 seconds to 5 minutes. RESULTS: Rapid changes (occurring over time spans of ≤60 seconds) in SAP and MAP assessed by oBPM were strongly correlated and showed excellent concordance with changes in invasive AP (worst-case Pearson correlation of 0.94 [0.88, 0.97] [95% confidence interval], concordance rate of 100% [100%, 100%], and angular concordance rate at ±30° of 100% [100%, 100%]). The trending ability tended to decrease progressively as the time span over which the changes occurred increased, reaching 0.89 (0.85, 0.91) (Pearson correlation), 97% (95%, 100%) (concordance rate), and 90% (85%, 94%) (angular concordance rate) in the worst case. Regarding accuracy and precision, oBPM-derived SAP values were shown to comply with AAMI criteria up to 2 minutes after calibration, whereas oBPM-derived MAP values were shown to comply with criteria at all times. CONCLUSIONS: Pulse oximeter waveform analysis was useful to track rapid changes in SAP and MAP during anesthesia induction. A good agreement with reference invasive measurements was observed for MAP up to at least 5 minutes after initial calibration. In the future, this method could be used to track changes in AP between intermittent oscillometric measurements and to automatically trigger brachial cuff inflation when a significant change in AP is detected.

General anesthesia in infants: neurobiological and neuropsychological concerns.

General anesthetics are crucial drugs for surgical interventions, which are indicated to induce analgesia, diminish pain, and reduce anxiety in order to facilitate invasive procedures. In pediatric patients, benefits of general anesthetics also include abolishment of motility. Besides their probed benefits on surgery, the recent warning of the Food and Drug Administration (FDA) on the use of general anesthetics in children yielded a controversy on their potential neurotoxic effects. In this review, the main facts of the cerebral development are studied, and the available evidence concerning the use of general anesthesia on the neuropsychological development of children is analyzed. Most of the studies found were uncontrolled retrospective cohorts for which conclusions are difficult to obtain. However, a few group of controlled studies, including the Mayo Anesthesia Safety in Kids study (MASK), have partially supported the FDA warning. Cumulated evidence appears to support the safety use of general anesthetics, but no conclusive data supporting that it may induce massive effects on the cognitive development of exposed children has been reported. Important evidence suggests that specific cognitive functions may result altered under long-term expositions. Such data must be considered for those involved in anesthetic procedures.

La anestesia general es una herramienta imprescindible para el proceso quirúrgico, ya que disminuye el dolor, reduce la ansiedad y genera inconsciencia. Sin ella, las cirugías serían dolorosas, riesgosas y emocionalmente traumáticas. La reciente emisión de una alerta sobre el uso de fármacos anestésicos en niños menores de 3 años por parte de la Food and Drug Administration (FDA) de los Estados Unidos generó controversia en torno a sus posibles efectos negativos. En este artículo se abordan los principales hitos del desarrollo neurobiológico del niño y se revisan las posibles consecuencias neuropsicológicas del uso de anestesia general en esta población. La mayoría de los reportes que abordan este tema son de tipo retrospectivo y arrojan resultados controversiales por sus inherentes dificultades metodológicas. Sin embargo, el estudio prospectivo sobre seguridad del uso de anestesia general en niños de la Clínica Mayo (MASK, Mayo Anesthesia Safety in Kids), junto con otros estudios a gran escala, han confirmado algunos datos obtenidos en los estudios experimentales que dieron sustento a la alerta emitida por la FDA. Así, las evidencias hasta ahora publicadas sugieren que el uso de anestesia general es seguro para el desarrollo cognitivo general del niño, aunque evidencian también alteraciones focalizadas en procesos cognitivos específicos que deben ser consideradas por el médico y la familia ante un procedimiento quirúrgico-anestésico.

Pediatric Patients with Previous Anaphylactic Reactions to General Anesthesia: a Review of Literature, Case Report, and Anesthetic Considerations.

PURPOSE OF REVIEW: It is rare to see pediatric patients with previous perioperative anaphylaxis receiving future anesthesia, but it is critical to understand how to choose assessments, interpret the results, and develop a future anesthetic plan. RECENT FINDINGS: Analysis of the results revealed that patients, at any age, regardless of sex and nationality, and the number of surgeries, have the risk of perioperative anaphylaxis while the risk of allergy increases as patients present multiple surgical events or have a previous history of atopy. 94.7% of pediatric patients with allergy testing after perioperative anaphylaxis tolerated subsequent general anesthesia without complications. Specific IgE tests, basophil activation tests, and skin tests are not available and suitable for all culprits. The early skin test could be considered a supplement for later testing. Drug challenge test is the golden standard but can only be used as the last resort. If general anesthesia is inevitable, avoidance of the culprit and use of alternative agents can help the patients prevent another potential recurrence. Full use of inhalation anesthesia without unnecessary neuromuscular blockade agents and avoidance of latex is recommended when the surgery is urgent or skin tests for children cannot be performed in time. This review summarizes characteristics of perioperative pediatric anaphylaxis, main tests for various drugs, and their sensitivities and specificities as well as recommendations as to how to implement safe anesthesia in the future.

Anestesia general en infantes: consideraciones neurobiológicas y neuropsicológicas / General anesthesia in infants: neurobiological and neuropsychological concerns

Resumen La anestesia general es una herramienta imprescindible para el proceso quirúrgico, ya que disminuye el dolor, reduce la ansiedad y genera inconsciencia. Sin ella, las cirugías serían dolorosas, riesgosas y emocionalmente traumáticas. La reciente emisión de una alerta sobre el uso de fármacos anestésicos en niños menores de 3 años por parte de la Food and Drug Administration (FDA) de los Estados Unidos generó controversia en torno a sus posibles efectos negativos. En este artículo se abordan los principales hitos del desarrollo neurobiológico del niño y se revisan las posibles consecuencias neuropsicológicas del uso de anestesia general en esta población. La mayoría de los reportes que abordan este tema son de tipo retrospectivo y arrojan resultados controversiales por sus inherentes dificultades metodológicas. Sin embargo, el estudio prospectivo sobre seguridad del uso de anestesia general en niños de la Clínica Mayo (MASK, Mayo Anesthesia Safety in Kids), junto con otros estudios a gran escala, han confirmado algunos datos obtenidos en los estudios experimentales que dieron sustento a la alerta emitida por la FDA. Así, las evidencias hasta ahora publicadas sugieren que el uso de anestesia general es seguro para el desarrollo cognitivo general del niño, aunque evidencian también alteraciones focalizadas en procesos cognitivos específicos que deben ser consideradas por el médico y la familia ante un procedimiento quirúrgico-anestésico.

Abstract General anesthetics are crucial drugs for surgical interventions, which are indicated to induce analgesia, diminish pain, and reduce anxiety in order to facilitate invasive procedures. In pediatric patients, benefits of general anesthetics also include abolishment of motility. Besides their probed benefits on surgery, the recent warning of the Food and Drug Administration (FDA) on the use of general anesthetics in children yielded a controversy on their potential neurotoxic effects. In this review, the main facts of the cerebral development are studied, and the available evidence concerning the use of general anesthesia on the neuropsychological development of children is analyzed. Most of the studies found were uncontrolled retrospective cohorts for which conclusions are difficult to obtain. However, a few group of controlled studies, including the Mayo Anesthesia Safety in Kids study (MASK), have partially supported the FDA warning. Cumulated evidence appears to support the safety use of general anesthetics, but no conclusive data supporting that it may induce massive effects on the cognitive development of exposed children has been reported. Important evidence suggests that specific cognitive functions may result altered under long-term expositions. Such data must be considered for those involved in anesthetic procedures.

Distinct effects of general anesthetics on lung metastasis mediated by IL-6/JAK/STAT3 pathway in mouse models.

Metastasis can occur following surgical resection of solid tumors and metastasis is the main cause of cancer death. The role of anesthetics used during surgery in cancer metastasis and the underlying mechanism remains largely unknown. Here we show that surgical dissection of primary tumors in mice under anesthesia with sevoflurane leads to significantly more lung metastasis than with propofol in both syngeneic murine 4T1 and xenograft human MDA-MB-231 breast cancer models. Sevoflurane increases the level of serum IL-6, which activates STAT3 and the infiltration of CD11b+ myeloid cells into the lung. Interruption of IL-6/JAK/STAT3 pathway by a JAK inhibitor AZD1480 reverses the pro-metastatic effect of sevoflurane and the associated increase of both activated STAT3 and infiltrated CD11b+ cells in 4T1 model. Our study provides the preclinical evidence informing the distinct effects of anesthetics on metastasis of breast cancers through change of cytokines and the tumor microenvironment.

Drug Challenge Tests With General Anesthetics: Predictive Value of Skin Tests.

BACKGROUND: The study of perioperative drug reactions remains a major challenge for both diagnosis and therapy. The lack of a standard assessment of allergy to general anesthetics and of data establishing the true value of skin tests for most drugs used in induction and maintenance of anesthesia, as well as the lack of commercially available reagents for in vitro tests, renders the study of these reactions problematic. The aims of this study were to provide a diagnostic protocol for drug challenge testing with general anesthetics, to establish an etiological diagnosis that is as specific as possible, and to determine the predictive value of skin tests. METHODS: Twenty-nine patients with perioperative drug reactions were included in the study from November 2008 to December 2018. RESULTS: We confirmed the high negative predictive value of the tests (96%-100%) in the case of propofol, rocuronium, and fentanyl. To our knowledge, this is the first study to describe drug challenge testing with general anesthetics and, therefore, to establish the true negative predictive value of skin tests, which leads to a definitive diagnosis and safer surgery. CONCLUSIONS: After assessing risks and benefits and considering the importance of this group of drugs, we conclude that drug challenge testing with general anesthetics is necessary. We propose a protocol for perioperative drug reactions that enables us to make a highly accurate etiological diagnosis with minimum risk for the patient.

Maternal exposure to volatile anesthetics induces IL-6 in fetal brains and affects neuronal development.

Most clinically used general anesthetics have demonstrated neurotoxicity in animal studies, but the related mechanisms remain unknown. Previous studies suggest that anesthetics affect neuronal development through neuroinflammation, and significant effects of neuroinflammation on neurogenesis and neuronal disease have been shown. In the present study, we treated pregnant mice with 2% sevoflurane for 3 h at gestational day 15.5 and analyzed the expression of proinflammatory cytokines, including IL-6 and IL-17, in fetal mice brains. Sevoflurane induced IL-6 mRNA significantly, but did not upregulate IL-17. Other volatile anesthetics, including isoflurane, enflurane, and halothane, induced IL-6 mRNA in fetal brains as well as sevoflurane, but propofol did not. Sevoflurane and isoflurane showed the same effects in cultured microglia and astrocytes, but not in neurons. Because IL-6 induction in fetal brains may affect neuronal precursor cells (NPCs), numbers of NPCs in the subventricular zone were studied, revealing that maternal sevoflurane treatment significantly increases NPCs in offspring at 8 weeks after birth (p8wk). But this effect was absent in IL-6 knockout mice. Finally, behavioral experiments also revealed that maternal sevoflurane exposure causes learning impairments in p8wk offspring. These findings collectively demonstrate that maternal exposure to volatile anesthetics upregulates IL-6 in fetal mice brains, and the effects could result in long-lasting influences on neuronal development.

Escape From Oblivion: Neural Mechanisms of Emergence From General Anesthesia.

The question of how general anesthetics suppress consciousness has persisted since the mid-19th century, but it is only relatively recently that the field has turned its focus to a systematic understanding of emergence. Once assumed to be a purely passive process, spontaneously occurring as residual levels of anesthetics dwindle below a critical value, emergence from general anesthesia has been reconsidered as an active and controllable process. Emergence is driven by mechanisms that can be distinct from entry to the anesthetized state. In this narrative review, we focus on the burgeoning scientific understanding of anesthetic emergence, summarizing current knowledge of the neurotransmitter, neuromodulators, and neuronal groups that prime the brain as it prepares for its journey back from oblivion. We also review evidence for possible strategies that may actively bias the brain back toward the wakeful state.

Anaesthetic neuroprotection in children: does it exist or is it all just bad?

PURPOSE OF REVIEW: In the last 20 years, data from studies of laboratory animals, including nonhuman primates, have provided ample evidence that general anaesthetic drugs cause pathological changes in developing central nervous system (neurotoxicity). Recently, a new area of research has been developed in order to recognize any possible actions that can attenuate anaesthetics neurotoxicity. This review aims to provide an overview of the recent literature on neuroprotection. RECENT FINDINGS: Neuroprotection includes a variety of actions that aim to preserve neuronal structures and/or function against insults caused by sedative and anaesthetic agents. Neuroprotective solutions include prevention of damage, such as postponing procedure, and counterbalance the damage. Mitigation of the neurotoxicity can be obtained through pharmacological protection, reducing cumulative dose or promoting neuroplasticity. Moreover, surgery and pain themselves might interfere with normal neurodevelopment in children and, in particular, treatment of pain plays a key role in preserving cortical activity and brain development. SUMMARY: Recent literature largely explores a variety of solutions in order to preserve and reduce the damage caused by anaesthetic agents. At the moment, none of the presented solutions regarding neuroprotection is applicable in clinical setting. Further research studies are needed.

Effect of Electroencephalography-Guided Anesthetic Administration on Postoperative Delirium Among Older Adults Undergoing Major Surgery: The ENGAGES Randomized Clinical Trial.

Importance: Intraoperative electroencephalogram (EEG) waveform suppression, often suggesting excessive general anesthesia, has been associated with postoperative delirium. Objective: To assess whether EEG-guided anesthetic administration decreases the incidence of postoperative delirium. Design, Setting, and Participants: Randomized clinical trial of 1232 adults aged 60 years and older undergoing major surgery and receiving general anesthesia at Barnes-Jewish Hospital in St Louis. Recruitment was from January 2015 to May 2018, with follow-up until July 2018. Interventions: Patients were randomized 1:1 (stratified by cardiac vs noncardiac surgery and positive vs negative recent fall history) to receive EEG-guided anesthetic administration (n = 614) or usual anesthetic care (n = 618). Main Outcomes and Measures: The primary outcome was incident delirium during postoperative days 1 through 5. Intraoperative measures included anesthetic concentration, EEG suppression, and hypotension. Adverse events included undesirable intraoperative movement, intraoperative awareness with recall, postoperative nausea and vomiting, medical complications, and death. Results: Of the 1232 randomized patients (median age, 69 years [range, 60 to 95]; 563 women [45.7%]), 1213 (98.5%) were assessed for the primary outcome. Delirium during postoperative days 1 to 5 occurred in 157 of 604 patients (26.0%) in the guided group and 140 of 609 patients (23.0%) in the usual care group (difference, 3.0% [95% CI, -2.0% to 8.0%]; P = .22). Median end-tidal volatile anesthetic concentration was significantly lower in the guided group than the usual care group (0.69 vs 0.80 minimum alveolar concentration; difference, -0.11 [95% CI, -0.13 to -0.10), and median cumulative time with EEG suppression was significantly less (7 vs 13 minutes; difference, -6.0 [95% CI, -9.9 to -2.1]). There was no significant difference between groups in the median cumulative time with mean arterial pressure below 60 mm Hg (7 vs 7 minutes; difference, 0.0 [95% CI, -1.7 to 1.7]). Undesirable movement occurred in 137 patients (22.3%) in the guided and 95 (15.4%) in the usual care group. No patients reported intraoperative awareness. Postoperative nausea and vomiting was reported in 48 patients (7.8%) in the guided and 55 patients (8.9%) in the usual care group. Serious adverse events were reported in 124 patients (20.2%) in the guided and 130 (21.0%) in the usual care group. Within 30 days of surgery, 4 patients (0.65%) in the guided group and 19 (3.07%) in the usual care group died. Conclusions and Relevance: Among older adults undergoing major surgery, EEG-guided anesthetic administration, compared with usual care, did not decrease the incidence of postoperative delirium. This finding does not support the use of EEG-guided anesthetic administration for this indication. Trial Registration: ClinicalTrials.gov Identifier: NCT02241655.