Is ethyl chloride the new nitrous oxide? A case report.

BACKGROUND: Over the last decade, there has been an emerging trend of recreational misuse of several drugs and inhaled solvent including ethyl chloride. This case report follows CARE guidelines and highlights, with supporting video, the neurological features of ethyl chloride intoxication. CASE PRESENTATION: A 48-year-old man was seen for the sudden occurrence of an unsteady gait with dizziness. His only medical history was a chronic and treated HIV infection without any complications. Clinical examination revealed a cerebellar syndrome associated with impairment of short-term memory. Biological and radiological workups were normal. After several days, the patient recalled ethyl chloride inhalation. He fully recovered after being discharged from hospital. CONCLUSION: Clinicians should recognise the clinical features and neurological manifestations of ethyl chloride intoxication due to the potential fatal cardiovascular complications of this intoxication.

Use of mixed gas pneumoperitoneum during minimally invasive surgery: a systematic review of human and mouse modelled laparoscopic interventions.

The formation of pneumoperitoneum involves the process of inflating the peritoneal cavity during laparoscopic and typically uses CO2 as the insufflation gas. This review aims to identify ideal gas mixtures for establishing the pneumoperitoneum with animal and human studies undertaken up to the writing of this review. A systematic search of PubMed, OVID, and clinicaltrials.gov was performed to identify studies on the utilisation of mixed gases in laparoscopic surgery, including non-randomised/randomised trials, animal and human studies, and studies with inflating pressures between 12 and 16 mmHg. ROBINS-I and RoB2 tool was used to assess the risk of bias. A narrative synthesis of results was performed due to the heterogeneity of the studies. 5 studies from the database search and 5 studies from citation search comprising 128 animal subjects and 61 human patients were found. These studies collated results based on adhesion formation (6 studies), pain scores (2 studies) and other outcomes, with results favouring the use of carbon dioxide + 10% nitrous oxide + 4% oxygen. This has shown a significant reduction in adhesion formation, pain scores and inflammation. The use of this gas mixture provides promising results for future practice. Several of the studies available require larger sample sizes to develop a more definitive answer on the effects of different gas mixtures. Furthermore, the number of confounding factors in randomised trials should be reduced so that each component of the current suggested gas mixture can be tested for safety and efficacy.

Perspectives on sustainable practices in the use of nitrous oxide for labour analgesia: A patient and staff survey.

BACKGROUND: Climate change has emerged as the single biggest global health threat of the twenty-first century. Nitrous oxide accounts for the largest carbon footprint amongst our use of anaesthetic gas. It is a potent greenhouse gas possessing a global warming potential of approximately 265 times that of carbon dioxide. Despite recent curtailment of its use, it remains extensively employed as an analgesic for women in labour. OBJECTIVES: Assessment of the opinions of post-natal women and staff on nitrous oxide use and to investigate whether knowledge of its environmental harm would influence their choice of labour analgesia. DESIGN: Postnatal women and healthcare staff were invited to participate in a survey of nitrous oxide use as a labour analgesic and knowledge of its effect of the environment. SETTING: A single-centre study in a major obstetric tertiary referral centre in Ireland in 2021. MAIN OUTCOME MEASURES: To evaluate the awareness and perceptions of postnatal women and staff regarding the environmental impact of nitrous oxide and if it would affect their decision to use it in the future. RESULTS: One hundred postnatal women and 50 healthcare staff completed the survey. One hundred and six post-natal women were invited to complete the survey, resulting in a response rate of 94%. Knowledge of nitrous oxide's environmental impact was low. After receiving information, 46% of patients were more inclined to seek epidural or request it earlier (54%) to limit their nitrous oxide use, while 51% would choose an alternative analgesia to avoid nitrous oxide altogether. Overwhelmingly, 99% believed they had the right to know about these harmful effects when choosing an analgesic option. CONCLUSIONS: Patients should be informed of the environmental impact of nitrous oxide antenatally, empowering them to make informed decision on a climate friendly analgesic option if they wish.

Nitrous Oxide-induced Myeloneuropathy Due to Recreational Abuse.

BACKGROUND: The recreational use of nitrous oxide (N2O) has increased in recent years with a noticeable surge in the incidence of nitrous oxide-related myeloneuropathy. OBJECTIVES: To raise awareness of increasing myeloneuropathy due to recreational nitrous oxide misuse in Israel. METHODS: We conducted a case series documenting the clinical and investigative features of eight patients presenting with nitrous oxide-induced myeloneuropathy who were admitted to our departments. RESULTS: Paresthesia was the chief complaint in all patients, with sensory gait ataxia being a common feature, which was often accompanied by Romberg's sign and mild lower limb weakness. Vitamin B12 levels were below the normal range in seven patients, accompanied by elevated homocysteine and methylmalonic acid levels. Magnetic resonance imaging scans revealed hyperintense signals in the dorsal columns of the cervical spine. All patients improved following vitamin B12 injections. CONCLUSIONS: Enhancing awareness, prompting the use of appropriate investigations, and advocating for timely treatment are needed to overcome the risks associated with nitrous oxide misuse.

Inhaled methoxyflurane - an explorable alternative to nitrous oxide?

Nitrous oxide is a widely used and well-established form of inhalation sedation in dentistry. Its properties have a wide margin of safety and allow for anxious, paediatric and adult patients to receive dental treatment with minimal impact upon discharge. Nitrous oxide has drawbacks, however, including its environmental impact and need for specialist equipment. Methoxyflurane is another drug which could prove to be an alternative to nitrous oxide. Methoxyflurane's use has proved popular within emergency medicine in Australia and New Zealand for its potent analgesic effects and recognition of its anxiolytic effect. As a result, its use in invasive outpatient procedures has now become popular. Unfortunately, there is very limited evidence of its use within dentistry as a form of inhalation sedation and analgesic. A wider evidence base should be established, as methoxyflurane could prove to be an effective and environmentally friendly alternative to nitrous oxide.

The Role of Nitrous Oxide in Minor Pediatric Procedures in the Emergency Department: A Systematic Review.

BACKGROUND: Pediatric patients undergoing minor, but painful procedures in an Emergency Department (ED) need adequate relief of pain and distress to prevent long term negative effects and adversely impact procedures. Inhaled nitrous oxide (N2O) is a needle-free pain management option. We conducted a systematic review to determine whether N2O is as effective as local anesthesia in minor procedures. The purpose of this study was to evaluate available evidence regarding analgesic effectiveness of N2O in pediatric patients. METHODS: We searched MEDLINE, Embase, Cochrane and Cinahl databases for controlled trials published in English with pediatric patients in an ED treated with N2O compared to local anesthesia and with pain as primary outcome. Adverse events was one of the secondary outcomes. The GRADE system was used to rate the overall quality of evidence. RESULTS: We included seven studies with a total of 371 patients. Two studies showed N2O was equally effective in pain treatment as local anesthesia. Five studies showed N2O combined with local anesthesia is more effective in reducing pain than local anesthesia alone. None of the included studies reported major adverse effects. The quality of evidence is low. CONCLUSIONS: N2O can have an important contribution in pain management, but should be combined with local anesthesia for optimal pain management in pediatric patients undergoing minor, but painful procedures in an ED. LEVEL OF EVIDENCE: IV.

Comparison of Efficacy and Safety of Midazolam versus Nitrous Oxide as Sedative Agents during Paediatric Dental Treatment: A Systematic Review / Comparison of Efficacy and Safety of Midazolam versus Nitrous Oxide as Sedative Agents during Paediatric Dental Treatment: A Systematic Review

ABSTRACT Objective: To identify and study the existing literature on the efficacy and safety of midazolam compared to inhalation of nitrous oxide in children undergoing dental treatment. Material and Methods: Electronic resources such as PubMed Central, Cochrane Database of Systematic Reviews, Lilacs, Science Direct, and SIGLE were thoroughly searched. The title scan was used to find randomised controlled trials reviewed for inclusion by reading the abstract. Studies comparing the sedative, behavioural, and anxiolytic effects and safety in children undergoing dental treatment under midazolam and nitrous oxide inhalation were included. The Cochrane Reviews system software, Revman 5.4.1, was used to assess the quality of the included studies. Results: 11328 articles were identified by screening the electronic databases, of which 10906 were eliminated after titles were read and duplicates were removed. Ten full-text articles were examined, of which three were excluded as they did not match the eligibility criteria. Hence, a total of 7 studies were included. Midazolam and nitrous oxide inhalation were not statistically different in terms of the success of treatment and behaviour modification. However, midazolam showed a deeper level of sedation and resulted in amnesia in more children when compared to nitrous oxide sedation. All of the included studies were found to have a high risk of bias. Conclusion: Though all the studies included showed an increased risk of bias, midazolam and nitrous oxide inhalation seem equally effective sedative agents for controlling behaviour in children undergoing dental treatment. Midazolam shows a deeper sedation level when given orally and produces a higher rate of anterograde amnesia.

Combination of inhaled nitrous oxide and oral opioids induces long-lasting analgesic effects in patients with neuropathic pain: ProtoTOP study post hoc exploratory analyses.

ABSTRACT: Experimental studies have suggested that nitrous oxide-induced analgesia depends on interactions with opioids. On the basis of these results, we hypothesized that the effects of inhaled nitrous oxide/oxygen (N 2 O/O 2 ) 50%-50% equimolar mixture (EMONO) on patients with neuropathic pain would be higher in those receiving concomitant opioids. To test this hypothesis, we did exploratory post hoc analyses of our recently published ProtoTOP study to compare the effects of EMONO and placebo in patients with or without concomitant opioid treatment. A total of 92 patients of the 221 (ie, 41.6%) included in the ProtoTOP study were concomitantly treated with opioids. In contrast with our previous analyses, average pain intensity was significantly decreased in comparison with placebo one week after the last treatment administration in patients treated with opioids, but not in those treated without opioid, and this effect was maintained over the 4-week follow-up period. Neuropathic pain symptom inventory (NPSI total and subscores) was also significantly more decreased after inhalation of EMONO in comparison with placebo only in patients receiving opioids. The proportion of patients with at least 30% pain reduction and of those reporting an overall improvement with the Patient Global Impression of Change were significantly higher only in this population of patients. In conclusion, these results complement our previous analyses with the identification of a specific population of responders to EMONO inhalation in patients with neuropathic pain. As suggested by experimental studies, we hypothesized that these long-lasting analgesic effects could depend on the anti-N-methyl-D-aspartate properties of N 2 O.

Procedural analgesia with nitrous oxide at home for epidermolysis bullosa: A case report.

RATIONALE: Epidermolysis bullosa (EB) is an inherited disease characterized by fragile skin with painful blistering, which requires lifelong skin and wound care. This case report describes the use of inhaled nitrous oxide (N2O) for procedural pain control at home during wound care in a young man with severe dystrophic EB. To our knowledge, only 1 case was reported by Ingelmo et al in 2017 regarding the use of N2O at home in a 4-year-old-child. To date, no such attempt has been made in adult patients. PATIENT CONCERNS: Our patient was a 28-year-old man. Frequent blisters appear spontaneously, and are often preceded by erythema and itching. Patient required daily treatment daily consisting of lancing blisters with a needle and emptying them by compression. DIAGNOSES: Severe recessive dystrophic EB diagnosed at the time of delivery. INTERVENTIONS: Procedural pain control was managed by the auto-administration of an inhaled N2O and air gas mixture. OUTCOMES: Conscious sedation with N2O leads to beneficial effects, such as reduction in dressing duration, acute procedural pain, local antibiotic needing, medication memory, anxiety, anticipatory pain, and fatigue after the dressing session. LESSONS: N2O analgesia is safe and effective, resulting in a significant reduction in procedural pain and an improvement in the quality of life of patients and their caregivers.

Multicenter Study Evaluating Nitrous Oxide Use for Labor Analgesia at High- and Low-Altitude Institutions.

BACKGROUND: Nitrous oxide (N2O) has been used nationally as an analgesic in many clinical settings. While neuraxial analgesia is still the most commonly used labor analgesic in the United States, there is increasing use of N2O in labor. Given the reduction in the partial pressure of gases at a higher altitude, N2O has been reported to have reduced analgesic properties. However, there is no study to date evaluating the impact of altitude on labor analgesia and N2O. METHODS: We conducted a multicenter retrospective data analysis of a N2O registry collected from 4 institutions over a 3-year period. We compared the impact of altitude on 50% N2O administration for labor analgesia, conversion rates to another analgesic modality, as well as collected side effect frequencies and conversion predictors. Multivariable regression models were used to compare clinical characteristics and outcomes between parturients at high and low altitudes, while adjusting for race, ethnicity, education, and age (logistic and linear regressions for categorical and quantitative outcomes, respectively). RESULTS: A total of 1856 laboring parturients (age 18-50) were included in the analysis. The odds of converting from 50% N2O to another analgesic modality had no statistically significant difference between high- versus low-altitude institutions (adjusted odds ratio [aOR], 1.13; 95% confidence interval [CI], 0.90-1.42; P = .3). Yet, when parturients at low altitude converted from N2O, they were more likely (aOR, 3.03; 95% CI, 1.59-5.88) to choose neuraxial analgesia instead of another analgesic modality when compared to high-altitude parturients. This is possibly due to higher epidural rates at the low-altitude institutions. When parturients at high altitude did convert into another modality, they were more likely (aOR, 2.19; 95% CI, 1.14-4.21) to convert due to inadequate pain relief compared to low-altitude parturients; however, missing data may have affected this finding. Laboring individuals at low altitude were significantly more likely to experience side effects (aOR, 2.13; 95% CI, 1.45-3.12). Those requiring labor augmentation, assisted vaginal, or cesarean delivery converted to neuraxial analgesia significantly more often than those that delivered via spontaneous vaginal delivery (P < .05) in both high- and low-altitude groups. CONCLUSIONS: This is the first study evaluating 50% N2O as a labor analgesic at high altitude. As expected, we found lower side effects at high altitude, likely due to the lower partial pressure of N2O. However, there was not a statistically significant increase in conversion from N2O to another analgesic modality at high altitude and no clinically significant differences in neonatal outcomes.

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.

A retrospective cohort study on red blood cell morphology changes in pre-school age children under nitrous oxide anesthesia.

BACKGROUND: Megaloblastic anemia or bone marrow changes could occur after prolonged nitrous oxide inhalation via vitamin B12 inactivation related DNA synthesis impairment. Previous researches have studied hematological changes with nitrous oxide exposure, but only in adults or adolescents. Pre-school age children with active hematopoietic red bone marrow are more vulnerable to potential side effects of nitrous oxide and might experience growth impairment. The purpose of our study was to analyze red blood cell morphology changes under nitrous oxide anesthesia in pre-school age children. METHODS: One hundred thirty-six children under 5 years old scheduled for hemivertebra resection were analyzed. According to fresh gas type in anesthesia records, 71 children who received nitrous oxide in oxygen during anesthesia maintenance were categorized into the nitrous oxide group and the other 65 who received air in oxygen were the air group. Complete blood counts in perioperative period were assessed for anemia, macrocytosis, microcytosis, anisocytosis, hyperchromatosis and hypochromatosis. The peak value and change percentage were calculated for mean corpuscular volume and red cell distribution width. RESULTS: Forty-two children in the air group (64.6%) and 30 in the nitrous oxide group (42.3%) developed anemia (P = 0.009). None developed macrocytosis in both groups. Postoperative mean corpuscular volume peaked (mean [95% confidence interval]) at 83.7(82.9-84.4) fL, and 83.2(82.4-83.9) fL and postoperative red cell distribution width at 13.8% (13.4-14.2%), and 13.9% (13.6-14.2%) for the air group and the nitrous oxide group. Both the relative change of mean corpuscular volume (P = 0.810) and red cell distribution width (P = 0.456) were similar between the two groups. CONCLUSIONS: No megaloblastic red blood cell changes were observed with nitrous oxide exposure for 4 h in pre-school age children undergoing hemivertebra resection.

The effect of saline versus air for cuff inflation on the incidence of high intra-cuff pressure in paediatric MicroCuff® tracheal tubes: a randomised controlled trial.

The use of cuffed tracheal tubes in paediatric anaesthesia is now common. The use of nitrous oxide in anaesthesia risks excessive tracheal tube cuff pressures, as nitrous oxide can diffuse into the cuff during the course of surgery. The aim of this single-centre, prospective, randomised controlled trial was to compare the effect of saline versus air for the inflation of tracheal tube cuffs on the incidence of excessive intra-operative cuff pressure in children undergoing balanced anaesthesia with nitrous oxide. Children (age ≤ 16 y) were randomly allocated to receive either saline (saline group) or air (air group) to inflate the cuff of their tracheal tube. The pressure in the tracheal tube cuff was measured during surgery and brought down to the initial inflation level if it breached a safe limit (25 cmH2 O). Post-extubation adverse respiratory events were noted. Data from 48 patients (24 in each group), aged 4 months to 16 y, were analysed. The requirement for reduction in intra-cuff pressure occurred in 1/24 patients in the saline group, compared with 16/24 patients in the air group (p < 0.001). The incidence of extubation-related adverse events was similar in the saline and air groups (15/24 vs. 13/24, respectively; p = 0.770). The use of saline to inflate the cuff of paediatric cuffed tubes reduces the incidence of high intra-cuff pressures during anaesthesia. This may provide a pragmatic extra safety barrier to help reduce the incidence of excessive tracheal cuff pressure when nitrous oxide is used during paediatric anaesthesia.

Recreational Nitrous Oxide Abuse: Prevalence, Neurotoxicity, and Treatment.

Nitrous oxide (N2O), also known as "laughing gas," is a colorless, nonirritating gas. Clinically, it is widely used as an inhaled anesthetic, analgesic, and anxiolytic. In recent years, recreational abuse of N2O has become increasingly common, especially among young adults and adolescents, but many of them lack awareness of the possible side effects associated with this drug. N2O abuse can damage multiple systems, especially the nervous system, but the exact mechanism of N2O toxicity remains controversial. At present, an increasing number of cases of nervous system damage caused by N2O abuse have been reported both at home and abroad. Discontinuation of N2O use and timely supplementation with vitamin B12 are essential for a good prognosis. Long-term abuse without timely treatment will eventually lead to irreversible neurological damage. In this article, we discuss the epidemiology of N2O abuse, neurotoxicity mechanisms, clinical manifestations, relevant auxiliary examinations, treatments, and prognosis to improve social awareness of N2O exposure risk, especially among users and clinicians.

Plaque erosion causing ST-elevation myocardial infarction after consumption of cannabis and N2O in a 27-year old man: a case report.

BACKGROUND: The recreational drugs cannabis and nitrous oxide (N2O) are known for pro-atherogenic effects and are associated with an elevated risk of myocardial infarction. These cardiovascular effects might be underestimated by the public. Culprit-lesion composition of myocardial infarctions associated with cannabis and N2O has been unknown so far. This case report aims to raise the awareness of the adverse cardiovascular effects of cannabis and N2O and reports, for the first time, optical coherence tomography (OCT) findings of the culprit lesion. CASE PRESENTATION: This is a case report of a 27-year old man with anterior ST-segment-elevation myocardial infarction (STEMI) after intoxication with cannabis and N2O. Coronary angiography and OCT revealed plaque erosion with subsequent subtotal thrombotic occlusion of the left anterior descending artery that was successfully treated with 1 drug-eluting stent. The patient was symptom free at 6 months follow-up and had been able to abstain from drug consumption. CONCLUSIONS: This is the first case to demonstrate the association between cannabis and N2O abuse and plaque erosion on OCT in a young man with STEMI. In contrast to smoking, whose adverse effects are well-known, the cardiovascular effects of cannabis and N2O might be underestimated. These adverse effects should gain more awareness in the public to prevent early vascular events in young adults.