Does vitamin B12 deficiency explain psychiatric symptoms in recreational nitrous oxide users? A narrative review.

Background Recreational use of nitrous oxide (N2O) is associated with many side effects, of which neurological complications are most common. Nitrous oxide abuse is also associated with psychiatric symptoms, but these have received less attention so far. Vitamin B12 deficiency may play a role in the development of these psychiatric symptoms.Aims To explore the relationship among the occurrence of recreational nitrous oxide-induced psychiatric symptoms, accompanying neurological symptoms, vitamin B12 status and choice of treatment.Methods A retrospective search for case reports was conducted across multiple databases (Pubmed, Embase, Web of Science, PsycINFO and CINAHL). Keywords included variants of "nitrous oxide", "case report" and "abuse". No restrictions to language or publication date were applied.Results The search retrieved 372 articles. A total of 25 case reports were included, representing 31 patients with psychiatric complications following nitrous oxide abuse. The most often reported symptoms were: hallucinations (n = 16), delusions (n = 11), and paranoia (n = 11). When neurological symptoms were present, patients were treated more frequently with vitamin B12 supplementation.Conclusions This review highlights the need to recognize that psychiatric symptoms may appear in association with nitrous oxide use. Approximately half of the cases that presented with nitrous oxide-induced psychiatric complaints did not show neurological symptoms, and their vitamin B12 concentration was often within the hospital's reference range. Psychiatrists and emergency physicians should be aware of isolated psychiatric symptoms caused by recreational nitrous oxide abuse. We suggest asking all patients with new psychiatric symptoms about nitrous oxide use and protocolizing the management of nitrous oxide-induced psychiatric symptoms.

Association between well-characterized gene polymorphisms and the hypnosis response caused by sevoflurane-induced anaesthesia.

WHAT IS KNOWN AND OBJECTIVE: Sevoflurane is the most widely used volatile anaesthetic in clinical practice. It exhibits a hypnotic (unconsciousness) effect and causes a loss of reaction to noxious stimuli (immobility). However, to date, the mechanism of action of sevoflurane is poorly understood. In this study, we explored the effects of genetic variations on sevoflurane-induced hypnosis. METHODS: Sixty-six SNPs in 18 candidate genes were genotyped using MALDI-TOF MassARRAY in a discovery cohort containing 161 patients administered sevoflurane. Significant polymorphisms were assessed in a validation cohort containing 265 patients. RESULTS AND DISCUSSION: Three polymorphisms (GRIN1 rs28681971, rs79901440 and CHRNA7 rs72713539) were significantly associated with the time to loss of consciousness in patients treated with sevoflurane in the discovery cohort; among them, GRIN1 rs28681971 showed a significant association even after false discovery rate (FDR) correction (pFDR  = 0.039). Following the validation analysis, GRIN1 rs28681971 and rs79901440 showed statistical efficacy (pFDR  = 0.027, 0.034). Combined assessments and meta-analysis of the results of the two cohorts indicated that the C carriers of rs28681971 and T carriers of rs79901440 in GRIN1 require a longer time to achieve unconsciousness. WHAT IS NEW AND CONCLUSION: These findings suggest that GRIN1 polymorphisms are associated with sevoflurane-induced unconsciousness. Thus, the genotypes of GRIN1 may serve as novel and meaningful biomarkers for sevoflurane-induced unconsciousness.

Multiple criteria decision analysis approach to consider therapeutic innovations in the emergency department: The methoxyflurane organizational impact in acute trauma pain.

BACKGROUND: Acute trauma pain is poorly managed in the emergency department (ED). The reasons are partly organizational: ED crowding and rare trauma care pathways contribute to oligoanalgesia. Anticipating the organizational impact of an innovative care procedure might facilitate the decision-making process and help to optimize pain management. METHODS: We used a multiple criteria decision analysis (MCDA) approach to consider the organizational impact of methoxyflurane (self-administered) in the ED, introduced alone or supported by a trauma care pathway. A MCDA experiment was designed for this specific context, 8 experts in emergency trauma care pathways (leading physicians and pharmacists working in French urban tertiary hospitals) were recruited. The study involved four steps: (i) Selection of organizational criteria for evaluating the innovation's impact; (ii) assessment of the relative weight of each criterion; (iii) choice of appropriate scenarios for exploring the organizational impact of MEOX under various contexts; and (iv) software-assisted simulation based on pairwise comparisons of the scenarios. The final outcome measure was the expected overall organizational impact of methoxyflurane on a 0-to-100 scale (score >50: positive impact). RESULTS: Nine organizational criteria were selected. "Mean length of stay in the ED" was the most weighted. Methoxyflurane alone obtained 59 as a total score, with a putative positive impact for eight criteria, and a neutral effect on one. When a trauma care pathway was introduced concomitantly, the impact of methoxyflurane was greater overall (score: 75) and for each individual criterion. CONCLUSIONS: Our model highlighted the putative positive organizational impact of methoxyflurane in the ED-particularly when supported by a trauma care pathway-and the relevance of expert consensus in this particular pharmacoeconomic context. The MCDA approach could be extended to other research fields and healthcare challenges in emergency medicine.

Brain interstitial fluid drainage and extracellular space affected by inhalational isoflurane: in comparison with intravenous sedative dexmedetomidine and pentobarbital sodium.

Brain interstitial fluid drainage and extracellular space are closely related to waste clearance from the brain. Different anesthetics may cause different changes of brain interstitial fluid drainage and extracellular space but these still remain unknown. Herein, effects of the inhalational isoflurane, intravenous sedative dexmedetomidine and pentobarbital sodium on deep brain matters' interstitial fluid drainage and extracellular space and underlying mechanisms were investigated. When compared to intravenous anesthetic dexmedetomidine or pentobarbital sodium, inhalational isoflurane induced a restricted diffusion of extracellular space, a decreased extracellular space volume fraction, and an increased norepinephrine level in the caudate nucleus or thalamus with the slowdown of brain interstitial fluid drainage. A local administration of norepinephrine receptor antagonists, propranolol, atipamezole and prazosin into extracellular space increased diffusion of extracellular space and interstitial fluid drainage whilst norepinephrine decreased diffusion of extracellular space and interstitial fluid drainage. These findings suggested that restricted diffusion in brain extracellular space can cause slowdown of interstitial fluid drainage, which may contribute to the neurotoxicity following the waste accumulation in extracellular space under inhaled anesthesia per se.

Sevoflurane anesthesia during pregnancy in mice induces cognitive impairment in the offspring by causing iron deficiency and inhibiting myelinogenesis.

Maternal anesthetic exposure during pregnancy is associated with an increased risk of cognitive impairment in offspring. The balance of cerebral iron metabolism is essential for the development of brain tissue. Iron deficiency affects the myelinogenesis and nerve tissue development, especially in fetus or infant, which has a key role in cognitive function. We aimed to investigate whether maternal sevoflurane (Sev) exposure caused cognitive impairment in offspring through inducing iron deficiency and inhibiting myelinogenesis. Pregnant mice (gestation stage day 14) were treated with 2% Sev for 6 h. Cognitive function of offspring mice was determined by the Morris water maze and Context fear conditioning test. Iron levels were assayed by Perl's iron staining and synchrotron imaging. Hippocampus and cortex tissues or cerebral microvascular endothelial cells of offspring mice (postnatal day 35) were harvested and subjected to Western blot and/or immunhistochemistry to assess ferritin, transferrin receptor 1(TfR1), Ferroportin-1 (FpN1), myelin basic protein (MBP), tight junction protein ZO-1, occludin, and claudin-5 levels. Beginning with postnatal day 30, the offspring were treated with iron therapy for 30 days, and the indicators above were tested. Our results showed Sev dramatically decreased the iron levels of brain and impaired cognitive function in offspring mice. Sev decreased the expression of heavy chain ferritin (FtH), light chain ferritin (FtL), MBP, ZO-1, occludin, claudin-5, and FpN1, and increased TfR1 in hippocampus and cortex or cerebral microvascular endothelial cells of offspring mice, indicating that Sev caused the iron deficiency and impaired the myelinogenesis in the brain of offspring. Interestingly, iron therapy prompted the myelinogenesis and improved impaired cognitive function at postnatal day 60. Our research uncovered a new mechanism which showed that iron deficiency induced by Sev and myelin formation disorder due to decreased iron of brain may be an important risk factor for cognitive impairment in offspring. It was necessary for offspring to be supplied iron supplement whose mother suffered exposure to sevoflurane during pregnancy.

Ketofol performance to reduce postoperative emergence agitation in children undergoing adenotonsillectomy.

Background: Emergence agitation is a reformed state of mindfulness, which starts with a sudden form of anesthesia and progresses through the early repossession age. Thus, the purpose of this study is to evaluate 1:3 ketofol performance on children 3-15 years old undergoing adenotonsillectomy.Methods: A total of 60 children aged 3-15 years undergoing adenotonsillectomy were randomly allocated to receive low-dose ketamine 0.15 mg/kg followed by propofol 0.45 mg/kg i.v. ketofol (1:3) about 10 min before the end of surgery in comparison to 60 children aged 3-15 years who received only normal saline and dextrose. Anesthesia was induced and maintained with sevoflurane. Postoperative pain and EA were assessed with objective pain score (OPS) and the Pediatric Anesthesia Emergence Delirium (PAED) scale, respectively. EA was defined as a PAED 10 points. Recovery profile and postoperative complications were also recorded.Results: The incidence and severity of EA were found significantly lower in the ketofol group in comparison to the control group with a percentage of (13.33% vs 48.33%) (8% vs 15%) respectively (P < 0.05). Also, the time for interaction from anesthetic tainted to extubating in the ketofol set was significantly less than in the control group (P < 0.05). Interestingly, there are no opposing events such as nausea, laryngospasm, bronchospasm, hypotension, bradycardia, bleeding, or postoperative respiratory depression (respiratory rate: <16) were noticed in the ketofol supervision (P > 0.05). Moreover, the heart rate was meaningfully higher in the control group starting at the time of tracheal extubating in comparison to the children undergone ketofol (P < 0.05). Alert score and time from painkilling tainted till liberation from PACU showed substantial significant changes at ketofol set (P < 0.05).Conclusion: Ketofol (1:3) shows significant performance to reduce postoperative agitation in the children undergone adenotonsillectomy.

Monitoring Depth of Hypnosis: Mid-Latency Auditory Evoked Potentials Derived aepEX in Children Receiving Desflurane-Remifentanil Anesthesia.

BACKGROUND: The aepEXplus monitoring system, which uses mid-latency auditory evoked potentials to measure depth of hypnosis, was evaluated in pediatric patients receiving desflurane-remifentanil anesthesia. METHODS: Seventy-five patients, 1-18 years of age (stratified for age; 1-3, 3-6, 6-18 years, for subgroup analyses), were included in this prospective observational study. The aepEX and the bispectral index (BIS) were recorded simultaneously, the latter serving as a reference. The ability of the aepEX to detect different levels of consciousness, defined according to the University of Michigan Sedation Scale, investigated using prediction probability (Pk), and receiver operating characteristic (ROC) analysis, served as the primary outcome parameter. As a secondary outcome parameter, the relationship between end-tidal desflurane and the aepEX and BIS values were calculated by fitting in a nonlinear regression model. RESULTS: The Pk values for the aepEX and the BIS were, respectively, .68 (95% CI, 0.53-0.82) and .85 (95% CI, 0.73-0.96; P = .02). The aepEX and the BIS had an area under the ROC curve of, respectively, 0.89 (95% CI, 0.80-0.95) and 0.76 (95% CI, 0.68-0.84; P = .04). The maximized sensitivity and specificity were, respectively, 81% (95% CI, 61%-93%) and 86% (95% CI, 74%-94%) for the aepEX at a cutoff value of >52, and 69% (95% CI, 56%-81%) and 70% (95% CI, 57%-81%) for the BIS at a cutoff value of >65. The age-corrected end-tidal desflurane concentration associated with an index value of 50 (EC50) was 0.59 minimum alveolar concentration (interquartile range: 0.38-0.85) and 0.58 minimum alveolar concentration (interquartile range: 0.41-0.70) for, respectively, the aepEX and BIS (P = .69). Age-group analysis showed no evidence of a difference regarding the area under the ROC curve or EC50. CONCLUSIONS: The aepEX can reliably differentiate between a conscious and an unconscious state in pediatric patients receiving desflurane-remifentanil anesthesia.

Conscious Sedation in Dentistry.

Invasive dental procedures can be performed only with local anesthesia; in some cases, it may be useful to combine the administration of drugs to obtain anxiolysis with local anesthesia. Sedation required level should be individually adjusted to achieve a proper balance between the needs of the patient, the operator, and the safety of the procedure. Surgical time is an important factor for post-operative phases, and this could be greatly increased by whether the patient interrupts the surgeon or if it is not collaborative. In this manuscript some dentistry-used methods to practice conscious sedation have been evaluated. This manuscript could be a useful reading on the current state of conscious sedation in dentistry and an important starting point for future perspectives. Surely the search for safer drugs for our patients could have beneficial effects for them and for the clinicians.

Sedation and analgesia in interventional radiology: Where do we stand, where are we heading and why does it matter?

The aims of this review were to describe the rationale and the techniques of sedation in interventional radiology, and to compile the safety and efficacy results available so far in the literature. A systematic MEDLINE/PubMed literature search was performed. Preliminary results from several studies demonstrated the feasibility, the efficacy and the safety of using sedative techniques in interventional radiology. Beyond pharmacological sedation and clinical hypnosis, digital sedation could reduce the anxiety and pain associated with interventional radiology procedures.

Use of nitrous oxide in children. / Bruk av lystgass hos barn.

BACKGROUND: In July 2013, the Department of Paediatric and Adolescent Medicine at Østfold Hospital Trust introduced nitrous oxide as an option for procedural sedation of children and adolescents. MATERIAL AND METHOD: During the period 13 July 2013-25 August 2017, 311 procedures were performed with nitrous oxide in 238 patients aged 4-17 years. Age, sex, type and duration of procedure, any supplementary medications, complications and whether the procedure would previously have required general anaesthesia, were recorded in a form. The child rated the effectiveness of nitrous oxide using a graded age-appropriate 10-point pain scale, and the nurse rated it as good, moderate or none. RESULTS: The children reported a median pain score of 2/10 (interquartile range 0-4), and nurses rated effectiveness as good in 247 of 304 (81 %) cases. For 43 % of procedures, the nurse felt that general anaesthesia would have been necessary had the department not had access to nitrous oxide. Adverse effects, most often dizziness, were reported in 110 of 311 procedures (35 %). In 7 of 311 procedures (2 %), the patient experienced adverse effects that resulted in stoppage of the procedure. The procedure was completed in 286 (92 %) children. INTERPRETATION: Nitrous oxide is a useful option for children who require procedural sedation, and means that more procedures can be performed without general anaesthesia.

Resolution of Acute Priapism in Two Children With Sickle Cell Disease Who Received Nitrous Oxide.

BACKGROUND: Nitrous oxide (N O) is an inhalational medication that has anxiolytic, amnestic, potent venodilatory and mild-to-moderate analgesic properties commonly used in the emergency department (ED) setting. N2 O has a rapid onset of action (<5 minutes) and recovery (<5 minutes) and can be quickly titrated to effect without the need for IV access. It has few side effects, does not require renal or hepatic metabolism for excretion and has no reports of allergic reaction. Priapism is a serious complication of sickle cell disease (SCD) affecting approximately 35% of males, with an adverse impact on quality of life. Treatment options are limited and not evidence based, including hydration, alkalization, analgesia, oxygenation to prevent further sickling, and exchange transfusion. Patients who do not respond within 4 hours often require a painful invasive procedure that includes aspiration of blood from the corpus cavernosum and phenylephrine injections. Case reports have described a therapeutic benefit from oral pseudoephedrine, sildenafil, and intravenous (IV) arginine, however controlled clinical trials are lacking. Although a 50:50 nitrous oxide/oxygen mix is commonly used in France to enhance analgesia in patients with SCD and vasoocclusive pain events (VOE) not sufficiently responding to IV morphine, there are no reports of its use to treat priapism. We describe the effects of N2 O for the treatment of acute priapism associated with SCD in a pediatric ED. METHODS: This is a case series of two adolescent boys with Hb-SS who on 3 separate occasions presented to the ED with acute priapism that failed oral therapy (pseudoephedrine and opioids). N2 O gas was utilized to help facilitate IV catheter placement. RESULTS: In each presentation (at ages 8 and 10 years for patient 1; age 15 years for patient 2), the patient experienced complete resolution of the priapism within 4-15 min of receiving N2 O (max 60%). The patients were discharged from the ED following each presentation and had no recurrence during the subsequent week. CONCLUSIONS: Priapism is a challenging complication of SCD associated with long-term morbidity and a paucity of treatment options. Opioids are commonly used. Given the risks and inconsistent results of current recommended therapy, N2 O may represent a potential opioid-sparing treatment option for priapism presenting to the ED that warrants further investigation. Although anecdotal, N2 O inhalation is an intervention to consider during a time when a treating ED physician may have few alternatives.

EVALUATION OF ACUPUNCTURE POINTS GOVERNING VESSELS 1 AND 26 ON ANESTHETIC RECOVERY OF EASTERN BOX TURTLES ( TERRAPENE CAROLINA CAROLINA).

Intramuscular administration of anesthetic agents in chelonians may result in a prolonged (≥1 hr) return of spontaneous movement and breathing, which increases the probability for peri- and postoperative complications. The acupuncture point governing vessel (GV)-26 has been demonstrated to reduce anesthetic recovery times from inhalant anesthesia in other species. In this study, 30 eastern box turtles (EBT; Terrapene carolina carolina), presented to the Turtle Rescue Team at North Carolina State University's College of Veterinary Medicine for treatment of aural abscess, were divided into four groups: control (no treatment); GV-26 acupuncture; GV-1 and GV-26 acupuncture; or GV-1 and GV-26 electroacupuncture. Turtles receiving either GV-1 and GV-26 acupuncture or GV-1 and GV-26 electroacupuncture had a significantly reduced time to return of voluntary movement ( P = 0.012 and P = 0.006, respectively), a significantly reduced time to response of limb extension ( P = 0.03 and P < 0.001, respectively), and a significantly reduced time to anesthetic recovery ( P < 0.05 and P < 0.01, respectively). Therefore, the use of either GV-1 and GV-26 acupuncture or GV-1 and GV-26 electroacupuncture produces significant reductions in anesthetic recovery time in EBTs that have received injectable anesthetics.

Treatment outcomes of using inhalation sedation for comprehensive dental care.

AIM: To assess the outcomes of dental treatment under inhalation sedation within a UK specialist hospital setting. METHODS: This was a retrospective cohort study of the case notes of patients under 17 years of age who received dental treatment using inhalation sedation at a UK specialist setting during the period 2006-2011. Treatment outcomes were categorised into five groups: (1) treatment completed as planned, (2) modified treatment completed, (3) treatment abandoned in sedation unit and patient referred for treatment under general analgesia (GA), (4) treatment abandoned in sedation unit and patient referred for treatment under local analgesia (LA), (5) child failed to return to complete treatment. RESULTS: In total, the case notes of 453 patients were evaluated. The mean age of the patients was 10.3 ± 2.9 years. Treatment was completed successfully in 63.6% of the cases, 15.9% were referred for treatment under GA, 11.2% failed to return to complete the treatment, 7.1% received modified treatment completed, and only 2.2% were referred for treatment under LA. Treatment outcomes were significantly associated with patient`s age (p = 0.002). The treatment outcome "treatment abandoned and child referred to be treated under GA" had significantly lower mean patient ages than the other outcomes. CONCLUSIONS: The majority of children referred for inhalation sedation, completed their course of treatment. A significantly higher proportion of those in the younger age group required GA to complete their treatment.

[Clinical observation of wrist-ankle needle therapy combined with patient controlled intravenous analgesia for pain after laparoscopic surgery for eccyesis].

OBJECTIVE: To observe the effect difference between wrist-ankle needle therapy combined with patient controlled intravenous analgesia (PCIA) and simple PCIA for pain after laparoscopic surgery for eccyesis. METHODS: Ninety-eight patients were assigned into an observation group and a control group by random number table, 49 cases in each one. General static inhalation combined anesthesia was used in the two groups. Simple PCIA for pain was applied in the control group. Wrist-ankle needle therapy at bilateral ankle area 1 and 2 combined with PCIA were implemented in the observation group. The pain state of cut was recorded by visual analogue scale (VAS) 1 h, 2 h, 6 h, 12 h, 24 h, 36 h and 48 h after surgery. The total effective rates and adverse reaction rates within 48 h after surgery were compared between the two groups. RESULTS: The VAS scores 6 h, 12 h and 24 h after surgery in the observation group were lower than those in the control group (all P<0.01), and the scores in the other time points were not statistically different (all P>0.05). The total effective rate of the observation group was 98.0% (48/49), which was better than 83.7% (41/49) of the control group (P<0.05). The adverse reaction rate of the observation group was 12.2% (6/49), and that of the control group was 69.4% (34/49), with statistical difference (P<0.01). CONCLUSION: Wrist-ankle needle therapy combined with PCIA can effectively relieve pain after laparoscopic surgery for eccyesis, and reduce adverse reaction rate after surgery.

Intraoperative mandibular nerve block with peripheral nerve stimulator for temporomandibular joint ankylosis.

We describe the use of peripheral nerve stimulator for mandibular nerve block intraoperatively in a 4.5year old child with complete temporomandibular joint ankyloses. The block was not possible preoperatively, therefore, it was administered after release of ankyloses. The use of peripheral nerve stimulator increased the chances of a successful block. No intraoperative analgesics and muscle relaxants were required. Postoperative pain relief was excellent. Peripheral nerve stimulator is an easy way of for accurate needle tip placement for mandibular nerve block in patients with distorted anatomy.

Recent trends in the anesthetic management of craniotomy for supratentorial tumor resection.

PURPOSE OF REVIEW: The article reviews the recent evidence on the anesthetic management of patients undergoing craniotomy for supratentorial tumor resection. RECENT FINDINGS: A rapid recovery of neurological function after craniotomy for supratentorial tumor allows for the prompt diagnosis of intracranial complications and possibly an early hospital discharge. Intraoperative esmolol infusion was shown to reduce the anesthetic requirements, and may facilitate a more rapid recovery of neurological function. Outpatient craniotomy for supratentorial tumor resection has been associated with several clinical and economic benefits, but has not gained widespread use because of skepticism and medical-legal concerns. Awake craniotomy is associated with advantageous outcomes compared with surgery under general anesthesia, and is regarded as the standard of care for tumors that reside in or in close proximity to the eloquent brain. Recent studies have demonstrated that intraoperative electroacupuncture, dexmedetomidine, pregabalin, and lidocaine may facilitate postcraniotomy pain management. The use of volatile anesthetic agents in cancer surgery is associated with a worse survival compared with intravenous anesthetics, possibly by hindering immunologic defenses against cancer cells. SUMMARY: Recent evidence has yielded valuable information regarding anesthetic management of patients undergoing supratentorial tumor craniotomy. Despite a plethora of studies that compare short-term outcomes using different anesthetic and analgesic regimens, randomized controlled trials that examine the long-term outcomes (i.e., neurocognitive function, quality of life, tumor recurrence, and survival) that are of particular interest to patients are needed.

Effects of magnesium sulfate and propofol on the minimum alveolar concentration preventing motor movement in sevoflurane-anesthetized dogs.

OBJECTIVE To evaluate the effect of MgSO4, alone and in combination with propofol, on the minimum alveolar concentration preventing motor movement (MACNM) in sevoflurane-anesthetized dogs. ANIMALS 6 healthy purpose-bred adult male Beagles (least squares mean ± SEM body weight, 12.0 ± 1.1 kg). PROCEDURES Dogs were anesthetized 3 times at weekly intervals. The MACNM was measured 45 minutes after induction of anesthesia (baseline; MACNM-B) and was determined each time by use of a noxious electrical stimulus. Treatments were administered as a loading dose and constant rate infusion (CRI) as follows: treatment 1, MgSO4 loading dose of 45 mg/kg and CRI of 15 mg/kg/h; treatment 2, propofol loading dose of 4 mg/kg and CRI of 9 mg/kg/h; and treatment 3, MgSO4 and propofol combination (same doses used previously for each drug). A mixed-model ANOVA and Tukey-Kramer tests were used to determine effects of each treatment on the percentage decrease from MACNM-B. Data were reported as least squares mean ± SEM values. RESULTS Decrease from MACNM-B was 3.4 ± 3.1%, 48.3 ± 3.1%, and 50.3 ± 3.1%, for treatments 1, 2, and 3, respectively. The decrease for treatments 2 and 3 was significantly different from that for treatment 1; however, no significant difference existed between results for treatments 2 and 3. CONCLUSIONS AND CLINICAL RELEVANCE MgSO4 did not affect MACNM, nor did it potentiate the effects of propofol on MACNM. Administration of MgSO4 in this study appeared to provide no clinical advantage as an anesthetic adjuvant.

Changes in thalamo-frontal interaction under different levels of anesthesia in rats.

Anesthesia is thought to be mediated by inhibiting the integration of information between different areas of the brain. Long-range thalamo-cortical interaction plays a critical role in inducing anesthesia-related unconsciousness. However, it remains unclear how this interaction change according to anesthetic depth. In this study, we aimed to investigate how different levels of anesthesia affect thalamo-frontal interactions. Prior to the experiment, electrodes were implanted to record local field potentials (LFPs). Isoflurane (ISO) was administered and LFPs were measured in rats from four different brain areas (left frontal, right frontal, left thalamus and right thalamus) at four different anesthesia levels: awake, deep (ISO 2.5vol%), light (ISO 1vol%) and recovery. Spectral granger causality (Spectral-GC) were calculated at the measured areas in accordance with anesthetic levels. Anesthesia led to a decrease in connectivity in the thalamo-frontal direction and an increase in connectivity in the frontal-thalamic direction. The changes in thalamo-frontal functional connectivity were prominent during deep anesthesia at high frequency bands. The connection strengths between the thalamus and the frontal area changed depending on the depth of anesthesia. The relationships between anesthetic levels and thalamo-frontal activity may shed light on the neural mechanism by which different levels of anesthesia act.

Attenuation of High-Frequency (50-200 Hz) Thalamocortical Electroencephalographic Rhythms by Isoflurane in Rats Is More Pronounced for the Thalamus Than for the Cortex.

BACKGROUND: Thalamocortical electroencephalographic rhythms in gamma (30-80 Hz) and high-gamma (80-200 Hz) ranges have been linked to arousal and conscious processes. We have recently shown that propofol causes a concentration-dependent attenuation of the power of thalamocortical rhythms in the 50 to 200 Hz range and that this effect is far more pronounced for the thalamus. To determine whether similar attenuation occurs with other anesthetics, we characterized the concentration-effect relationship of the inhaled anesthetic isoflurane on the spectral power of these rhythms. METHODS: Local field potentials were recorded from the barrel cortex and ventroposteromedial thalamic nucleus in 9 chronically instrumented rats to measure spectral power in the gamma/high-gamma range (30-200 Hz). Rats were placed in an airtight chamber and isoflurane was administered at 0.75%, 1.1%, and 1.5% concentrations. Spectral power was assessed during baseline, at the 3 isoflurane concentrations after 30 minutes for equilibration, and during recovery over 4 frequency bands (30-50, 51-75, 76-125, and 126-200 Hz). Unconsciousness was defined as sustained loss of righting reflex. Multiple linear regression was used to model the change in power (after logarithmic transformation) as a function of concentration and recording site. P values were corrected for multiple comparisons. RESULTS: Unconsciousness occurred at the 1.1% concentration in all animals. Isoflurane caused a robust (P ≤ 0.008) linear concentration-dependent attenuation of cortical and thalamic power in the 30 to 200 Hz range. The concentration-effect slope for the thalamus was steeper than for the cortex in the 51 to 75 Hz (P = 0.029) and 76 to 200 Hz (P < 0.001) ranges but not for the 30 to 50 Hz range (P = 0.320). Comparison with our previously published propofol data showed that slope for cortical power was steeper with isoflurane than with propofol for all frequency bands (P = 0.033). For thalamic power, the slope differences between isoflurane and propofol were not statistically significant (0.087 ≤ P ≤ 0.599). CONCLUSIONS: Isoflurane causes a concentration-dependent attenuation of the power of thalamocortical rhythms in the 30 to 200 Hz range, and this effect is more pronounced for the thalamus than for the cortex for frequencies >50 Hz. In comparison with propofol, isoflurane caused a greater attenuation in the cortex, but the effects on the thalamus were similar. Isoflurane and propofol cause common alterations of fast thalamocortical rhythms that may constitute an electrophysiologic signature of the anesthetized state.