Substance use disorder of equimolar oxygen-nitrous oxide mixture in French sickle-cell patients: results of the PHEDRE study.

BACKGROUND: In many countries, nitrous oxide is used in a gas mixture (EMONO) for short-term analgesia. Cases of addiction, with significant misuse, have been reported in hospitalized patients. Patients suffering from sickle cell disease (SCD) could represent a high-risk population for substance use disorder (SUD) due to their significant pain crisis and repeated use of EMONO. The objective of the PHEDRE study was to assess the prevalence of SUD for EMONO in French SCD patients. RESULTS: A total of 993 patients were included. Among 339 EMONO consumers, only 38 (11%) had a SUD, with very few criteria, corresponding mainly to a mild SUD due to a use higher than expected (in quantity or duration) and relational tensions with the care teams. Almost all patients (99.7%) were looking for an analgesic effect, but 68% of patients were also looking for other effects. The independent risks factors associated with at least one SUD criterion were: the feeling of effects different from the expected therapeutic effects of EMONO, at least one hospitalization for vaso occlusive crisis in the past 12 months and the presence of a SUD for at least one other analgesic drug. CONCLUSIONS: The use of EMONO was not problematic for the majority of patients. Manifestations of SUD that led to tensions with healthcare teams should alert and lead to an evaluation, to distinguish a true addiction from a pseudoaddiction which may be linked to an insufficient analgesic treatment related to an underestimation of pain in SCD patients. TRIAL REGISTRATION: Clinical Trials, NCT02580565. Registered 16 October 2015, https://clinicaltrials.gov/.

Sustained Mood Improvement with Laughing Gas Exposure (SMILE): Study protocol for a randomized placebo-controlled pilot trial of nitrous oxide for treatment-resistant depression.

BACKGROUND: Nitrous oxide has shown potentially as an efficacious intervention for treatment-resistant depression, yet there remains insufficient evidence pertaining to repeated administration of nitrous oxide over time and active placebo-controlled studies with optimal blinding. Thus, we aim to examine the feasibility and preliminary efficacy of a six-week follow up study examining the effects of a 4 week course of weekly administered nitrous oxide as compared to the active placebo, midazolam. METHODS: In this randomized, active placebo-controlled, pilot trial, 40 participants with treatment-resistant depression will receive either inhaled nitrous oxide (1 hour at 50% concentration) plus intravenous saline (100mL) or inhaled oxygen (1 hour at 50% concentration) plus intravenous midazolam (0.02 mg/kg in 100mL, up to 2mg) once per week, for 4 consecutive weeks. Participants will be followed up for 6 weeks starting from the first treatment visit. Primary feasibility outcomes include recruitment rate, withdrawal rate, adherence, missing data, and adverse events. The primary exploratory clinical outcome is change in Montgomery-Åsberg Depression Rating Scale (MADRS) score at day 42 of the study. Other exploratory clinical outcomes include remission (defined as MADRS score <10), response (defined as ≥ 50% reduction in MADRS score), and adverse side effects. DISCUSSION: This pilot study will provide valuable information regarding the feasibility and preliminary efficacy of repeated nitrous oxide administration over time for treatment-resistant depression. If feasible, this study will inform the design of a future definitive trial of nitrous oxide as an efficacious and fast-acting treatment for treatment-resistant depression. TRIAL REGISTRATION: ClinicalTrials.gov NCT04957368. Registered on July 12, 2021.

Nitrous oxide use in Canadian pediatric emergency departments: a survey of physician's knowledge, attitudes, and practices.

OBJECTIVES: Nitrous oxide (N2O) is an inhaled analgesic/ anxiolytic gas with evidence supporting its safety and efficacy for distressing procedures in children. Despite this, its use is not consistent across Canadian pediatric emergency departments (EDs). We aimed to characterize a) physicians' knowledge and practices with N2O and b) site-specific N2O protocols in Canadian pediatric EDs to help optimize its use nationally. METHODS: This cross-sectional survey was distributed to physician members of Pediatric Emergency Research Canada (PERC) in early 2021. Survey items addressed practice patterns, clinician comfort, and perceived barriers/ facilitators to use. Further, a representative from each ED completed a site-specific inventory of N2O policies and procedures. RESULTS: N2O was available in 40.0% of 15 pediatric EDs, with 83.3% of these sites having written policies in place. Of 230 distributed surveys, 67.8% were completed with mean (SD) attending experience of 14.7 (8.6) years and 70.1% having pediatric emergency subspecialty training. Of the 156 respondents, 48.7% used N2O in their clinical practice. The most common indications for use were digit fracture/ dislocation reduction (69.7%), wound closure (60.5%), and incision & drainage (59.2%). Commonly perceived facilitators were N2O equipment availability (73.0% of 156) and previous clinical experience (71.7% of 156). Of the 51.3% of physicians who reported not using N2O, 93.7% did not have availability at their site; importantly, the majority indicated a desire to acquire access. They identified concerns about ventilation/ scavenging systems (71.2% of 80) and unfamiliarity with equipment (52.5% of 80) as the most common barriers to use. CONCLUSIONS: Despite evidence to support its use, only half of Canadian pediatric ED physicians surveyed use N2O in their clinical practice for treating procedure-related pain and distress. Increased availability of N2O equipment, protocols, and training may improve clinicians' abilities to better manage pediatric acute pain and distress in the ED.

RéSUMé: OBJECTIFS: Le protoxyde d'azote (N2O) est un gaz analgésique/anxiolytique inhalé dont l'innocuité et l'efficacité ont été démontrées lors d'interventions pénibles chez l'enfant. Malgré cela, son utilisation n'est pas uniforme dans les services d'urgences pédiatriques (SU) du Canada. Nous avons cherché à caractériser a) les connaissances et les pratiques des médecins en matière de N2O et b) les protocoles de N2O spécifiques à un site dans les urgences pédiatriques canadiennes afin d'aider à optimiser son utilisation à l'échelle nationale. MéTHODES: Cette enquête transversale a été distribuée aux médecins membres de Recherche d'urgence pédiatrique Canada (PERC) au début de 2021. Les questions de l'enquête portaient sur les modes de pratique, l'aisance du clinicien et les obstacles/facilitateurs perçus pour l'utilisation. En outre, un représentant de chaque SU a dressé un inventaire des politiques et procédures N2O propres à chaque site. RéSULTATS: La N2O était disponible dans 40,0% des 15 services d'urgence pédiatriques, et 83,3% de ces sites avaient mis en place des politiques écrites. Sur 230 enquêtes distribuées, 67,8% ont été réalisées avec une expérience moyenne (SD) de 14,7 (8,6) ans et 70,1% ont suivi une formation en surspécialité pédiatrique d'urgence. Sur les 156 répondants, 48,7% utilisaient le N2O dans leur pratique clinique. Les indications les plus courantes étaient la réduction des fractures digitales et des luxations (69,7%), la fermeture des plaies (60,5%) et l'incision et le drainage (59,2%). Les facilitateurs généralement perçus étaient la disponibilité de l'équipement N2O (73,0% sur 156) et l'expérience clinique antérieure (71,7% sur 156). Parmi les 51,3% de médecins qui ont déclaré ne pas utiliser de N2O, 93,7% n'avaient pas de disponibilité sur leur site; il est important de noter que la majorité d'entre eux ont indiqué qu'ils souhaitaient y avoir accès. Ils ont identifié les préoccupations concernant les systèmes de ventilation/de récupération (71,2% sur 80) et la méconnaissance de l'équipement (52,5% sur 80) comme étant les obstacles les plus courants à l'utilisation de l'appareil. CONCLUSIONS: Malgré les données probantes à l'appui de son utilisation, seulement la moitié des médecins canadiens des urgences pédiatriques interrogés utilisent le N2O dans leur pratique clinique pour traiter la douleur et la détresse liées à l'intervention. Une plus grande disponibilité de l'équipement N2O, des protocoles et de la formation peut améliorer les capacités des cliniciens à mieux gérer la douleur aiguë et la détresse pédiatrique aux urgences.

Use of nitrous oxide in the treatment of major depressive disorder and treatment-resistant major depressive disorder: A systematic review and meta-analysis nitrous oxide in depressive disorders.

Major Depressive Disorder (MDD) has, as a conventional treatment, pharmacological therapy with selective monoamine reuptake inhibitors. However, the medication does not always have a rapid action for exacerbated cases, and moreover, it is estimated that 15 to 30% of patients do not respond effectively to conventional treatment, leading to 'treatment-resistant depressive mood disorder' (TRD). Thus, it is necessary to search for new therapeutic methods for exacerbated and resistant cases. The objective of the study was to evaluate the therapeutic effects of nitrous oxide (N2O) in patients with MDD and TRD. The study was characterized as a systematic review of randomized clinical trials. Search strategy was developed using the keywords "nitrous oxide," "treatment-resistant depression," "Depression disorder," and their synonyms, searched in the databases MEDLINE, EMBASE, LILACS, and American Psychological Association. Four articles were included in the systematic review, with two of them being utilized for the meta-analysis, which comprised a total of 23 patients with MDD and 86 with TRD. A standardized mean difference (SMD) for the HDRS score at 24 h of -2.36 was found, with a 95% confidence interval (CI) of -3.37 to -1.34 (p < 0.0001; I2 = 46%). For the evaluation of the score after one week, an SMD of -0.60, 95% CI of -1.13 to -0.07 (p = 0.03; I2 = 0%) was found. In conclusion, N2O has a rapid action for managing decompensated patients, with a potential therapeutic effect for TRD. However, more studies needed to determine N2O's effectiveness duration.

Nitrous oxide provided during intensive physiotherapy for shoulder adhesive capsulitis does not improve function: A randomised controlled trial.

BACKGROUND: There is no consensus on treatment for adhesive capsulitis of the shoulder. Physiotherapy is often used to increase range of motion but individuals may experience pain during mobilisation. OBJECTIVES: The objective of this study was to determine whether rehabilitation under N2O for shoulder AC improved pain and function more than rehabilitation alone (with placebo gas). METHOD: A randomised, 1:1 parallel arm, double-blind study in 4 university hospital outpatient centres. Adults with adhesive capsulitis for at least 3 months with intact cartilage were included. Participants were randomised in blocks of 4 and stratified by centre to receive 20 sessions of intensive physiotherapy over 10 days; the 10 morning sessions were performed with either nitrous oxide (intervention) or sham gas (placebo). PRIMARY OUTCOME: improvement in shoulder function at day 14 (D14) (Constant-Murley score). RESULTS: Seventy-five participants were included, and data from 69 were analysed: 37 in the placebo group and 32 in the intervention group. Improvements occurred in both groups after the intervention. No significant difference in the Constant-Murley score was found between groups at D14 (median score increase of 12.0, IQR 5.6; 19.5 points in placebo group vs. 13.7, 5.2; 18.2 in the N20 group, p = 0.78). Pain score during sessions reduced in the intervention group from the first to final session (-11.6, p = 0.053) but not for the placebo group (-4.2, p = 0.414). Seven serious adverse events were recorded, 4 in the intervention group and 3 in the placebo group, with 11 minor adverse events only in the intervention group (mostly shortness of breath). CONCLUSION: Nitrous oxide gas associated with intensive physiotherapy for shoulder adhesive capsulitis did not improve function, pain or quality of life more than physiotherapy alone. zHowever, pain experienced during physiotherapy sessions appeared lower. TRIAL REGISTRATION: Clinical Trial registration number NCT01087229.

Safety and efficacy of a nitrous oxide procedural sedation programme in a paediatric emergency department: a decade of outcomes.

BACKGROUND: Nitrous oxide (N2O) has multiple benefits in paediatric procedural sedation (PPS), but use is restricted by its limited analgesic properties. Analgesic potency could be increased by combining N2O and intranasal fentanyl (INF). We assessed safety and efficacy data from 10 years (2011-2021) of our N2O PPS programme. METHODS: Prospectively collected data from a sedation registry at a paediatric emergency department (PED) were reviewed. Total procedures performed with N2O alone or with INF, success rate, sedation depth and adverse events were determined. Contributing factors for these outcomes were assessed via regression analysis and compared between different N2O concentrations, N2O in combination with INF, and for physician versus nurse administered sedation. A post hoc analysis on factors associated with vomiting was also performed. RESULTS: 831 N2O procedural sedations were performed, 358 (43.1%) involved a combination INF and N2O. Nurses managed sedation in 728 (87.6%) cases. Median sedation depth on the University of Michigan Sedation Scale was 1 (IQR 1-2). Sedation was successful in 809 (97.4%) cases. Combination INF/N2O demonstrated higher median sedation scores (2 vs 1, p<0.001) and increased vomiting (RR 1.8, 95% CI 1.3 to 2.5), with no difference in sedation success compared with N2O alone. No serious adverse events (SAEs) were reported (desaturation, apnoea, aspiration, bradycardia or hypotension) regardless of N2O concentration or use of INF. 137 (16.5%) minor adverse events occurred. Vomiting occurred in 113 (13.6%) cases and was associated with higher concentrations of N2O and INF use, but not associated with fasting status. There were no differences in adverse events (RR 0.98, 95% CI 0.97 to 1.04) or success rates (RR 0.93, 95% CI 0.56 to 1.7) between physician provided and nurse provided sedation. CONCLUSION: N2O can provide effective PED PPS. No SAEs were recorded. INF may be an effective PPS adjunct but remains limited by increased rates of vomiting.

Comparison of basic and advanced behaviour management techniques between Colombian and Spanish parents during regular treatment and in emergency situations.

AIM: To evaluate the acceptance of behaviour management techniques by Spanish and Colombian parents used in paediatric dentistry and the influence of factors that determine their consent during regular treatment and in emergency situations. MATERIALS: An anonymous questionnaire was carried out in which 9 behaviour management techniques (BMTs) used in paediatric dentistry by Spanish and Colombian parents were evaluated in cases of regular dental treatment and in emergency situations (pain and/or dental trauma). The techniques evaluated were: tell-show-do (TSD), voice control, positive reinforcement, distraction, parental presence-absence, nitrous oxide, passive and active restraint, and general anaesthesia. The questionnaire also included information on the sociodemographic information about parents and their children, previous dental experience, and dental anxiety of the parents. The data were analysed using SPSSTM software, r. 26 of IBMTM. A value of p≤ 0.05 was considered as statically significant. RESULTS: A total sample of 124 questionnaire (62 from each country) was obtained. The basic BMT were the most accepted in both countries, especially by Spanish parents. In emergency situations, statistically significant differences were obtained in the acceptance of nitrous oxide and general anesthesia compared to their use in routine treatments (p<0.001). There were no significant differences in the preference of the techniques in relation to the age of the children or parental dental anxiety (p>0.05). An association was found between the socioeconomic status and the acceptance of nitrous oxide (p=0.005) and general anesthesia (p=0.004). CONCLUSION: The basic techniques were the most accepted by Spanish and Colombian parents. However, the Spanish parents had a better perception of both types of techniques compared to the Colombians. Their preference was influenced by factors such as annual income and need for urgent treatment of their children.

[Application effects of nitrous oxide and oxygen mixed inhalation technology on analgesia and sedation during debridement and dressing change in children with moderate or severe burns].

Objective: To investigate the application effects of nitrous oxide and oxygen mixed inhalation technology on analgesia and sedation during debridement and dressing change in children with moderate or severe burns. Methods: A retrospective non-randomized contemporary controlled study was conducted. From December 2019 to November 2021, 140 burn children with moderate or severe burns, aged 1 to 3 years, who met the inclusion criteria were admitted to Central Hospital Affiliated to Shandong First Medical University. During debridement and dressing change 3 to 14 days after injury, 42 children, including 23 males and 19 females, who received nurse-centered pain management mode and analgesia and sedation with nitrous oxide and oxygen mixed inhalation technology were included in nitrous oxide group (the dressing change process using the above-mentioned technology for the first time was selected for the follow-up study). Another 42 children, including 24 males and 18 females, were included in non-nitrous oxide group from 98 children who did not apply analgesia or sedation treatment during dressing change with stratified random sampling (one dressing change process was randomly selected for the follow-up study). The face, legs, activity, cry, and consolability scale and Ramsay sedation scale were used to evaluate the pain intensity and degree of sedation, respectively, at 30 minutes before dressing change (hereinafter referred to as before dressing change), immediately after debridement, and at 30 minutes after finishing dressing change (hereinafter referred to as after dressing change). After dressing change, the self-made satisfaction scale was used to evaluate the satisfaction degree of dressing change surgeons and guardians of children for analgesic effects during dressing change. The duration of dressing change and the healing time of deep partial-thickness burn wounds were recorded. The heart rate and percutaneous arterial oxygen saturation (SpO2) before, during, and after dressing change and the occurrence of adverse events such as nausea and vomiting during dressing change were recorded. Data were statistically analyzed with Mann-Whitney U test, chi-square test, analysis of variance for repeated measurement, independent sample t test, and Bonferroni correction. Results: There were no significant differences in the score of pain intensity and score of sedation degree between children in two groups before and after dressing change (P>0.05). Immediately after debridement, the score of pain intensity of children in nitrous oxide group was 2.5±0.7, which was significantly lower than 7.6±1.0 in non-nitrous oxide group (t=-26.69, P<0.05); the score of sedation degree of children in nitrous oxide group was 1.83±0.38, which was significantly higher than 1.21±0.42 in non-nitrous oxide group (t=7.15, P<0.05). After dressing change, the satisfaction degree scores of dressing change surgeons and guardians of children for analgesic effects during dressing change of children in nitrous oxide group were significantly higher than those in non-nitrous oxide group (with t values of 10.53 and 2.24, respectively, P<0.05). The dressing change duration of children in nitrous oxide group was significantly shorter than that in non-nitrous oxide group (t=-5.33, P<0.05). The healing time of deep partial-thickness burn wounds in children between the two groups had no significant difference (P>0.05). The heart rate of children in nitrous oxide group was significantly lower than that in non-nitrous oxide group during dressing change (t=-12.40, P<0.05), while the SpO2 was significantly higher than that in non-nitrous oxide group (t=5.98, P<0.05). During dressing change, 2 children had nausea and 1 child had euphoria in nitrous oxide group, while heart rate of all children in non-nitrous oxide group continued to be higher than the normal range. Conclusions: In the process of debridement and dressing change in children with moderate or severe burns, the use of nurse-centered pain management mode and the standardized use of nitrous oxide and oxygen mixed inhalation technology can safely and effectively control pain and sedation.

Nitrous oxide and hypnotherapy in paediatric dentistry.

AIM: Patient compliance is of paramount importance for proper dental treatment, which can be difficult to achieve in children due to anxiety and fear, hindering the therapeutic procedure. In addition to well-known sedation methods (pharmacological and nitrous oxide), further methods of approach are being tested, such as hypnotherapy. MATERIALS: The sample consisted of 150 children (90 males, 60 females). Paper questionnaires, frequency meter, nitrous oxide dispenser in association with the use of the television were exploited. At the end of treatment, subjective pain was assessed using the VAS scale, while objective pain was assessed using the FLACC scale and heart rate. This made it possible to compare two experimental groups, one treated with nitrous oxide, and the other with hypnotherapy. The control group was treated with classic behavioural approach techniques. The results obtained were analysed by SPSS Software (Statistical Package for Social Science, version 27) and the inferences between the results were calculated for confirmation. CONCLUSION: Hypnotherapy can be a valid substitute for nitrous oxide in paediatric dentistry.

Changes in cerebral connectivity and brain tissue pulsations with the antidepressant response to an equimolar mixture of oxygen and nitrous oxide: an MRI and ultrasound study.

Nitrous oxide (N2O) has recently emerged as a potential fast-acting antidepressant but the cerebral mechanisms involved in this effect remain speculative. We hypothesized that the antidepressant response to an Equimolar Mixture of Oxygen and Nitrous Oxide (EMONO) would be associated with changes in cerebral connectivity and brain tissue pulsations (BTP). Thirty participants (20 with a major depressive episode resistant to at least one antidepressant and 10 healthy controls-HC, aged 25-50, only females) were exposed to a 1-h single session of EMONO and followed for 1 week. We defined response as a reduction of at least 50% in the MADRS score 1 week after exposure. Cerebral connectivity of the Anterior Cingulate Cortex (ACC), using ROI-based resting state fMRI, and BTP, using ultrasound Tissue Pulsatility Imaging, were compared before and rapidly after exposure (as well as during exposure for BTP) among HC, non-responders and responders. We conducted analyses to compare group × time, group, and time effects. Nine (45%) depressed participants were considered responders and eleven (55%) non-responders. In responders, we observed a significant reduction in the connectivity of the subgenual ACC with the precuneus. Connectivity of the supracallosal ACC with the mid-cingulate also significantly decreased after exposure in HC and in non-responders. BTP significantly increased in the three groups between baseline and gas exposure, but the increase in BTP within the first 10 min was only significant in responders. We found that a single session of EMONO can rapidly modify the functional connectivity in the subgenual ACC-precuneus, nodes within the default mode network, in depressed participants responders to EMONO. In addition, larger increases in BTP, associated with a significant rise in cerebral blood flow, appear to promote the antidepressant response, possibly by facilitating optimal drug delivery to the brain. Our study identified potential cerebral mechanisms related to the antidepressant response of N2O, as well as potential markers for treatment response with this fast-acting antidepressant.

Is the equimolar mixture of oxygen and nitrous oxide (EMONO) associated with audiovisuals effective in reducing pain and side effects during peripheral venous access placement in children? Protocol for a single-centre randomised controlled trial from Italy.

INTRODUCTION: Nurses frequently place a peripheral venous catheter during children's hospitalisation. Many studies suggest treatment of venipuncture-related pain. The administration of an equimolar mixture of oxygen and nitrous oxide (EMONO) is employed for pain control; however, no studies have analysed the association between EMONO and audiovisuals.The purpose of the study is to evaluate the effect of EMONO administration when combined with audiovisuals (EMONO+Audiovisual) versus EMONO alone on perceived pain, side effects and level of cooperation during peripheral venous access placement in children aged 2-5 years. METHODS AND ANALYSIS: The first 120 eligible children admitted to the paediatric ward of the Lodi Hospital and presenting the indication for peripheral venous access will be enrolled. Sixty children will be randomly assigned to the experimental group (EMONO+Audiovisual) and 60 to the control group (EMONO alone).The Face, Legs, Activity, Cry, Consolability scale will be used to assess pain in the children aged 2-years old; pain in the children aged 3-5 years will be assessed using the Wong-Baker scale. The cooperation throughout the procedure will be measured using the Groningen Distress Rating Scale. ETHICS AND DISSEMINATION: The Milan Area 1 Ethics Committee approved the study protocol (Experiment Registry No. 2020/ST/295). The trial results will be presented at conferences and published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT05435118.

Empirical evidence for the neurocognitive effect of nitrous oxide as an adjunctive therapy in patients with treatment resistant depression: A randomized controlled study.

Nitrous oxide (N2O) has demonstrated an antidepressant effect for treatment-resistant depression (TRD), but no studies investigated the effects of N2O on different cognition domains. This study aimed to test whether N2O would display pro-cognitive effects. We conducted a double-blinded, placebo-controlled, randomized controlled trial, 44 patients with TRD were randomized to N2O group (one-hour inhalation of 50% N2O/50% oxygen) or placebo group (50% air/50% oxygen). Thirty-four patients completed cognitive tests at the pre-treatment phase, 1-week, and 2 weeks post-treatment including subjective cognitive function, processing speed, attention, and executive function. Although the antidepressant effect of N2O was not significant at 1 week, patients still showed better performance of executive function at 1 week after receiving N2O compared with the placebo. Moreover, this significant improvement still existed at 1 week after controlling for the change in depressive symptoms over-time. Additionally, no significant difference was observed in subjective cognitive function, processing speed, and attention between these two groups across the 2-week follow-up period. As the first study investigating the treatment effects of N2O on improving cognitive function in TRD patients, the current study indicated that N2O has a potential pro-cognitive effect on executive function and this effect might be independent from improvements in depressive symptoms.

Use of labor analgesia in trials of labor after previous cesarean section: A nationwide register-based analysis in Finland.

OBJECTIVES: The literature concerning the overall use of labor analgesia among women with trials of labor after cesarean section (TOLAC) is lacking. The primary aim of this study is to report the rate of different labor analgesia methods among women with TOLAC. The secondary aim was to compare the use of labor analgesia between women with the first TOLAC and control group consisting of nulliparous women. STUDY DESIGN: Data from the National Medical Birth Register was used to evaluate the usage of labor analgesia in TOLACs. The use of labor analgesia in the first TOLAC is compared to the pregnancies of nulliparous women. The analgesia methods were stratified into neuraxial analgesia, pudendal, paracervical, nitrous oxide, other medical, other non-medical, and no analgesia. These are analyzed as categorized dichotomy (yes or no) variables. RESULTS: A total of 38 596 TOLACs as second pregnancy of the mother was found during our study period. The control group consisted of a total of 327 464 pregnancies of nulliparous women. Epidural analgesia (61.6% vs 67.1%), nitrous oxide (56.1% vs 62.0%), and non-medical analgesia (30.1% vs 35.0%) were less consumed among women with TOLAC. The rate of spinal analgesia was higher among women with TOLAC (10.1% vs 7.6%) when compared to the control group. However, when only vaginal deliveries were included, the rate of labor analgesia increased especially in the TOLAC group. CONCLUSIONS: The main finding of this study is that women with TOLAC had a generally lower rate of labor analgesia. However, the rate of spinal analgesia was higher among women with TOLAC when compared to the control group, however. The results of this study inform midwives, obstetricians, and anesthesiologists on current practices and how to improve the analgetic treatment in TOLAC.

Eficacia del óxido nitroso como sedoanalgesia en pacientes pediátricos para procedimientos menores en áreas de hospitalización y urgencias / Efficacy of nitrous oxide as sedoanalgesia in pediatric patients for minor procedures in hospitalization and emergency areas. Bibliographic review

Objetivo: Conocer la utilización del óxido nitroso en procedimientos menores invasivos en pacientes pediátricos hospitaliza-dos y/o atendidos en servicios de urgencias. Método: Revisión bibliográfica. Se consultaron las bases Pub-Med, Scielo y Cochrane. Como criterios de inclusión se consideró idioma castellano e inglés y, últimos 10 años de publicación. Resultados: Se incluyeron 11 artículos: ensayos clínicos aleatoriza-dos, revisiones sistemáticas y estudios observaciones de cohortes. El intervalo de edad de utilización es de 3-6 años. La concentración recomendada del medicamento es 50-50. La eficacia del fármaco se describe para procedimientos dolorosos breves, accesos venosos, curas de heridas, sondajes vesicales, extracción de cuerpos extraños, drenajes de abscesos, punciones lumbares y reducción de fracturas, entre otros. Los efectos adversos son leves y se describen en menos del 10% de los estudios estando relacionados con mareos, cefalea, náuseas y vómitos. Se precisa administrar analgésico tópico previo. Profesionales de la salud, padres y pacientes refieren recomendar su uso. Discusión: Algunos estudios se realizan en muestras de edades amplias entre 1-18 años. Pocos estudios especifican el tipo de procedimiento que se llevó a cabo, y los que lo hacen coinciden en los tipos de procedimientos realizados. Todos los artículos recomiendan la administración de un analgésico previo. No todos los estudios hacen referencia a la satisfacción con la utilización del fármaco en los procedimientos. Se debe utilizar en procedimientos que no duren más de 15 minutos y los profesionales deben poseer competencias en el manejo de la vía aérea. Conclusiones: El óxido nitroso es un fármaco eficaz para la sedación en pacientes pediátricos. (AU)

Objective: To know the efficacy of nitrous oxide in minor invasive proce-dures in hospitalized pediatric patients or in emergency services. Methods and design: Bibliographic review. PubMed, Scielo and Cochrane databases were consulted. Spanish and English language and the last 10 years of publication were considered as inclusion criteria. Results: Eleven articles were included: randomized clinical trials, systematic reviews, and observational cohort studies. The age range was 3-6 years. The recommended concentration is 50-50. The efficacy of the drug is recom-mended for painful procedures, brief venous access, wound care, bladder catheters, extraction of foreign bodies, abscess drainage, lumbar punctures, reduction of fractures, among others. Adverse effects are mild and are de-scribed in less than 10% of the studies as being related to dizziness, head-ache, nausea, and vomiting. It is necessary to administer a previous topical analgesic. Health professionals, parents and patients report recommending its use. Discussion: Some studies are carried out in ages between 1-18 years. Few studies name the type of procedure that was carried out, those that do agree on the types of procedures performed. All the articles name the administration of a previous analgesic. Not all studies refer to satisfaction with the use of the drug in procedures. It should be used in procedures that last no more than 15 minutes and professionals should have skills in airway management.Conclusions: Nitrous oxide is an effective drug for sedation in pediatric patients. (AU)

Effectiveness of Nitrous Oxide versus Pethidine/Midazolam for Pain Relief in Minor Gynecological Operative Procedures: A Randomized Controlled Trial.

Aim and Objective: To compare the analgesic effectiveness of the patient-controlled inhaled nitrous oxide (Entonox®) with intravenous opioids (pethidine/midazolam) in reducing pain during minor gynecological operative procedures, including manual vacuum aspiration (MVA), fractional curettage and dilatation and curettage. Materials and Methods: Patients undergoing minor gynecological procedures from August 2021 to December 2022 were randomized to receive nitrous oxide or intravenous pethidine (50-75 micrograms) plus midazolam (2 mg). Pain scores during and post-procedure, satisfaction level, and side effects were assessed and compared. Results: A total of 106 patients met the inclusion criteria, including 53 in the pethidine/midazolam group and 53 in the nitrous oxide group. Baseline characteristics were comparable (p-value > 0.05). Pain scores during, immediately and 30 min after procedures were not significantly different in two groups (4.94 ± 3.15, 2.74 ± 2.57, 1.58 ± 2.13 vs. 5.47 ± 2.80, 2.98 ± 2.70, 1.64 ± 2.70; p-value: 0.174, 0.634, 0.889, for pethidine/midazolam vs. nitrous oxide group, respectively. Satisfaction scores were comparable in both groups (p-value > 0.05). However, the rate of side effects was significantly lower in the nitrous oxide group (3.8% vs. 28.3%; p-value 0.001). Additionally, the discharge scores showed a significantly faster recovery time in the nitrous oxide group at 60 and 90 min after the procedure; median (IQR): 10 (9-10) vs. 9 (8-10) and 10 (10-10) vs. 10 (8.5-10); p-value 0.002 and 0.029, respectively). Conclusions: Nitrous oxide is as effective as pethidine/midazolam for pain relief in minor gynecological operative procedures but associated with significantly lower side effects and significantly faster recovery time.

Pharmacological Management of the Dentally Anxious Patient.

Dental anxiety is a complex psychological problem in which patients associate negative feelings with the dental experience and is determined clinically through physiological and behavioral presentations. Self-reporting along with questionnaires and patient interviews can indicate the level of a patient's dental anxiety and guide the dentist in determining the appropriate management. Nonpharmacological methods of managing dental anxiety should be exhausted before pharmacological sedative techniques are considered. Nitrous oxide with oxygen is frequently used in the dental setting because of its relative safety, ease of use, and effectiveness for patients with mild to moderate dental anxiety. Oral sedation may be used for moderate to severely anxious patients and most typically consists of the administration of a single benzodiazepine drug prior to the dental appointment. Combination therapy of nitrous oxide with oxygen and oral sedation may be an option to increase the efficacy of both routes of sedation. Conscious intravenous sedation is a viable alternative for practitioners to use if they are adequately trained and certified to do so. Special considerations may apply for sedation of pediatric, elderly, and medically compromised patients and those with cognitive, physical, and/or behavioral disabilities. Sedation guidelines vary regionally, and dental professionals providing sedation must do so only with adequate training and certification as set by their local medical and dental regulatory governing bodies. This article provides a general review of the pharmacological management of dentally anxious patients as seen by a general dentist.

Brain function changes reveal rapid antidepressant effects of nitrous oxide for treatment-resistant depression:Evidence from task-state EEG.

Nitrous oxide has rapid antidepressant effects in patients with treatment-resistant depression (TRD), but its underlying mechanisms of therapeutic actions are not well understood. Moreover, most of the current studies lack objective biological indicators to evaluate the changes of nitrous oxide-induced brain function for TRD. Therefore, this study assessed the effect of nitrous oxide on brain function for TRD based on event-related potential (ERP) components and functional connectivity networks (FCNs) methods. In this randomized, longitudinal, placebo-controlled trial, all TRD participants were divided into two groups to receive either a 1-hour inhalation of nitrous oxide or a placebo treatment, and they took part in the same task-state electroencephalogram (EEG) experiment before and after treatment. The experimental results showed that nitrous oxide improved depressive symptoms better than placebo in terms of 17-Hamilton Depression Rating Scale score (HAMD-17). Statistical analysis based on ERP components showed that nitrous oxide-induced significant differences in amplitude and latency of N1, P1, N2, P2. In addition, increased brain functional connectivity was found after nitrous oxide treatment. And the change of network metrics has a significant correlation with decreased depressive symptoms. These findings may suggest that nitrous oxide improves depression symptoms for TRD by modifying brain function.

Proof-of-concept randomized controlled trial of single-session nitrous oxide treatment for refractory bipolar depression: Focus on cerebrovascular target engagement.

BACKGROUND: There remain few efficacious treatments for bipolar depression, which dominates the course of bipolar disorder (BD). Despite multiple studies reporting associations between depression and cerebral blood flow (CBF), little is known regarding CBF as a treatment target, or predictor and/or indicator of treatment response, in BD. Nitrous oxide, an anesthetic gas with vasoactive and putative antidepressant properties, has a long history as a neuroimaging probe. We undertook an experimental medicine paradigm, coupling in-scanner single-session nitrous oxide treatment of bipolar depression with repeated measures of CBF. METHODS: In this double-blind randomized controlled trial, 25 adults with BD I/II and current treatment-refractory depression received either: (1) nitrous oxide (20 min at 25% concentration) plus intravenous saline (n = 12), or (2) medical air plus intravenous midazolam (2 mg total; n = 13). Study outcomes included changes in depression severity (Montgomery-Asberg Depression Rating Scale scores, primary) and changes in CBF (via arterial spin labeling magnetic resonance imaging). RESULTS: There were no significant between-group differences in 24-h post-treatment MADRS change or treatment response. However, the nitrous oxide group had significantly greater same-day reductions in depression severity. Lower baseline regional CBF predicted greater 24-h post-treatment MADRS reductions with nitrous oxide but not midazolam. In region-of-interest and voxel-wise analyses, there was a pattern of regional CBF reductions following treatment with midazolam versus nitrous oxide. CONCLUSIONS: Present findings, while tentative and based on secondary endpoints, suggest differential associations of nitrous oxide versus midazolam with bipolar depression severity and cerebral hemodynamics. Larger studies integrating neuroimaging targets and repeated nitrous oxide treatment sessions are warranted.