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Piccialli F, Fiore M, Giurazza R, Falso F, Simeon V, Chiodini P, Russo D, Laino L. Efficacy and Safety of Nitrous Oxide (N 2O) Inhalation Sedation Compared to Other Sedative Agents in Dental Procedures: A Systematic Review with Meta-Analysis. MEDICINA (KAUNAS, LITHUANIA) 2025; 61:929. [PMID: 40428887 PMCID: PMC12113512 DOI: 10.3390/medicina61050929] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/18/2025] [Revised: 05/05/2025] [Accepted: 05/14/2025] [Indexed: 05/29/2025]
Abstract
Background and Objectives: Dental procedures can be distressing, particularly for patients who are anxious or uncooperative. In such cases, effective sedation not only facilitates the clinician's work but also enhances patient comfort and acceptance of dental care. Nitrous oxide (N2O) has been widely employed as a sedative agent in dental practice. This systematic review aimed to assess the efficacy and safety of N2O compared to alternative sedative agents and techniques in dental surgical procedures. Materials and Methods: This review protocol was prospectively registered on PROSPERO (CRD42020213429) and conducted in accordance with PRISMA guidelines. Results: A total of 1809 records were screened (1134 from Embase, 638 from PubMed, and 37 from CENTRAL). The meta-analysis focused on the following three primary outcomes: 1. Patient satisfaction: Eight studies comprising 422 participants (165 treated with N2O and 176 with other sedatives) were included. 2. Recall of the procedure: Five studies with a total of 288 patients (68 receiving N2O and 64 other agents) assessed patients' ability to recall tooth extraction. 3. Successful completion of the procedure: Three studies involving 1578 patients (434 treated with N2O and 989 with alternative sedation methods) were analyzed. Conclusions: No statistically significant differences were observed between N2O and other sedative techniques across all outcomes evaluated. Safety could not be adequately assessed as none of the included studies systematically investigated this outcome. Further high-quality research is warranted to rigorously evaluate the safety profiles of various sedation strategies in dental surgery.
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Affiliation(s)
- Francesca Piccialli
- Department of Women, Child and General and Specialized Surgery, University of Campania “Luigi Vanvitelli”, Via Luigi De Crecchio, 2, 80138 Naples, Italy; (F.P.); (R.G.)
| | - Marco Fiore
- Department of Women, Child and General and Specialized Surgery, University of Campania “Luigi Vanvitelli”, Via Luigi De Crecchio, 2, 80138 Naples, Italy; (F.P.); (R.G.)
| | - Roberto Giurazza
- Department of Women, Child and General and Specialized Surgery, University of Campania “Luigi Vanvitelli”, Via Luigi De Crecchio, 2, 80138 Naples, Italy; (F.P.); (R.G.)
- Department of Critical Care, AORN Ospedali dei Colli, Via Leonardo Bianchi, 80131 Naples, Italy;
| | - Fabrizio Falso
- Department of Critical Care, AORN Ospedali dei Colli, Via Leonardo Bianchi, 80131 Naples, Italy;
| | - Vittorio Simeon
- Medical Statistics Unit, Department of Public, Clinical and Preventive Medicine, University of Campania “Luigi Vanvitelli”, 80138 Naples, Italy
| | - Paolo Chiodini
- Medical Statistics Unit, Department of Public, Clinical and Preventive Medicine, University of Campania “Luigi Vanvitelli”, 80138 Naples, Italy
| | - Diana Russo
- Multidisciplinary Department of Medical-Surgical and Odontostomatological Specialties, University of Campania “Luigi Vanvitelli”, 80138 Naples, Italy; (D.R.); (L.L.)
| | - Luigi Laino
- Multidisciplinary Department of Medical-Surgical and Odontostomatological Specialties, University of Campania “Luigi Vanvitelli”, 80138 Naples, Italy; (D.R.); (L.L.)
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Agbo SMDN, Duan X, Wang L, Dong M, Wang Q, Cai X, Liu F. Comparative study of subacute combined degeneration of the spinal cord due to nitrous oxide abuse and vitamin B12 deficiency. Front Immunol 2025; 16:1567541. [PMID: 40356911 PMCID: PMC12066286 DOI: 10.3389/fimmu.2025.1567541] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2025] [Accepted: 04/07/2025] [Indexed: 05/15/2025] Open
Abstract
Objective The aim of this study was to compare the clinical presentations, nerve conduction studies, neuroimaging findings of subacute combined degeneration (SCD) caused by N2O abuse and primary vitamin B12 deficiency. The goal is to improve diagnostic accuracy, tailored therapeutic interventions, and ultimately enhancing patient outcomes in cases of SCD caused by N2O abuse. Methods This study was a retrospective case-control study which enrolled 23 patients diagnosed with N2O-induced subacute combined degeneration (N2O-SCD) and 20 patients with vitamin B12 deficiency-induced subacute combined degeneration (Vit B12-SCD) between 2015 and 2023. Clinical manifestations, physical examinations, laboratory tests, nerve conduction studies, and spinal cord MRI imaging results were collected. Additionally, age-matched healthy control groups were also included for comparative electrophysiological analysis, consisting of 23 young individuals and 21 elderly individuals corresponding to the N2O-SCD and Vit B12-SCD groups, respectively. Results The study found that compared to Vit B12-SCD, N2O-SCD patients exhibited more severe and extensive neurological damage. Both N2O-SCD and Vit B12- SCD patients may present with numbness or abnormal sensations, limb weakness, difficulty walking and inability to walk, but these are more severe and widespread in N2O-SCD patients. N2O-SCD patients showed significant decreases in limb strength, with common walking difficulties and paralysis. Additionally, N2O abuse patients more frequently exhibited psychiatric symptoms, especially memory loss, hallucinations and confusion. Both Vit B12-SCD and N2O-SCD can cause peripheral nerve demyelination and axonal damage, but it is more severe in the N2O-SCD group, with more damage in the lower limbs than in the upper limbs. The extensive nature of axonal damage also indicated a poor prognosis. The degree of spinal cord damage in the N2O-SCD group was more severe and affected longer segments. These results suggest that in addition to affecting vitamin B12, N2O also causes neurological damage through other mechanisms. Conclusion In summary, N2O-SCD leads to more severe clinical symptoms, peripheral nerve damage, and spinal cord injury than Vit B12-SCD. These differences guide the clinical treatment of N2O-SCD, requiring not only vitamin B12 supplementation but also an addition in neuroprotective treatments.
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Affiliation(s)
| | - Xiaohui Duan
- Department of Neurology, China-Japan Friendship Hospital, Beijing, China
| | - Li Wang
- Department of Neurology, The First Hospital of Tsinghua University, Beijing, China
| | - Mingrui Dong
- Department of Neurology, China-Japan Friendship Hospital, Beijing, China
| | - Qian Wang
- Department of Neurology, The First Hospital of Tsinghua University, Beijing, China
| | - Xiaojing Cai
- Department of Neurology, The First Hospital of Tsinghua University, Beijing, China
| | - Fang Liu
- Department of Neurology, The First Hospital of Tsinghua University, Beijing, China
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Cichon J, Joseph TT, Lu X, Wasilczuk AZ, Kelz MB, Mennerick SJ, Zorumski CF, Nagele P. Nitrous oxide activates layer 5 prefrontal neurons via SK2 channel inhibition for antidepressant effect. Nat Commun 2025; 16:2999. [PMID: 40180931 PMCID: PMC11968965 DOI: 10.1038/s41467-025-57951-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2024] [Accepted: 03/04/2025] [Indexed: 04/05/2025] Open
Abstract
Nitrous oxide (N2O) induces rapid and durable antidepressant effects. The cellular and circuit mechanisms mediating this process are not known. Here we find that a single dose of inhaled N2O induces rapid and specific activation of layer V (L5) pyramidal neurons in the cingulate cortex of rodents exposed to chronic stress conditions. N2O-induced L5 activation rescues a stress-associated hypoactivity state, persists following exposure, and is necessary for its antidepressant-like activity. Although NMDA-receptor antagonism is believed to be a primary mechanism of action for N2O, L5 neurons activate even when NMDA-receptor function is attenuated through both pharmacological and genetic approaches. By examining different molecular and circuit targets, we identify N2O-induced inhibition of calcium-sensitive potassium (SK2) channels as a key molecular interaction responsible for driving specific L5 activity along with ensuing antidepressant-like effects. These results suggest that N2O-induced L5 activation is crucial for its fast antidepressant action and this effect involves novel and specific molecular actions in distinct cortical cell types.
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Affiliation(s)
- Joseph Cichon
- Department of Anesthesiology and Critical Care, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
- Mahoney Institute for Neurosciences, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
| | - Thomas T Joseph
- Department of Anesthesiology and Critical Care, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
| | - Xinguo Lu
- Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA
- The Taylor Family Institute for Innovative Psychiatric Research, Washington University School of Medicine, St. Louis, MO, USA
| | - Andrzej Z Wasilczuk
- Department of Anesthesiology and Critical Care, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
| | - Max B Kelz
- Department of Anesthesiology and Critical Care, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
- Mahoney Institute for Neurosciences, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
| | - Steven J Mennerick
- Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA
- The Taylor Family Institute for Innovative Psychiatric Research, Washington University School of Medicine, St. Louis, MO, USA
| | - Charles F Zorumski
- Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA
- The Taylor Family Institute for Innovative Psychiatric Research, Washington University School of Medicine, St. Louis, MO, USA
| | - Peter Nagele
- Department of Anesthesia and Critical Care, University of Chicago, Chicago, IL, USA
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Williams E, Taujanskaite U, Kamboj SK, Murphy SE, Harmer CJ. Examining memory reconsolidation as a mechanism of nitrous oxide's antidepressant action. Neuropsychopharmacology 2025; 50:609-617. [PMID: 39825109 PMCID: PMC11845508 DOI: 10.1038/s41386-024-02049-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/11/2024] [Revised: 12/13/2024] [Accepted: 12/26/2024] [Indexed: 01/20/2025]
Abstract
There is an ongoing need to identify novel pharmacological agents for the effective treatment of depression. One emerging candidate, which has demonstrated rapid-acting antidepressant effects in treatment-resistant groups, is nitrous oxide (N2O)-a gas commonly used for sedation and pain management in clinical settings and with a range of pharmacological effects, including antagonism of NMDA glutamate receptors. A growing body of evidence suggests that subanaesthetic doses of N2O (50%) can interfere with the reconsolidation of maladaptive memories in healthy participants and across a range of disorders. Negative biases in memory play a key role in the onset, maintenance, and recurrence of depressive episodes, and the disruption of affective memory reconsolidation is one plausible mechanism through which N2O exerts its therapeutic effects. Understanding N2O's mechanisms of action may facilitate future treatment development in depression. In this narrative review, we introduce the evidence supporting an antidepressant profile of N2O and evaluate its clinical use compared to other treatments. With a focus on the specific memory processes that are thought to be disrupted in depression, we consider the effects of N2O on memory reconsolidation and propose a memory-based mechanism of N2O antidepressant action.
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Affiliation(s)
- Ella Williams
- Department of Psychiatry, Oxford University, Warneford Hospital, Oxford, UK
| | - Ursule Taujanskaite
- Clinical Psychopharmacology Unit, Research Department for Clinical, Educational and Health Psychology, University College London, 1-19 Torrington Place, London, UK
| | - Sunjeev K Kamboj
- Clinical Psychopharmacology Unit, Research Department for Clinical, Educational and Health Psychology, University College London, 1-19 Torrington Place, London, UK
| | - Susannah E Murphy
- Department of Psychiatry, Oxford University, Warneford Hospital, Oxford, UK
- Oxford Health NHS Foundation Trust, Warneford Hospital, Oxford, UK
| | - Catherine J Harmer
- Department of Psychiatry, Oxford University, Warneford Hospital, Oxford, UK.
- Oxford Health NHS Foundation Trust, Warneford Hospital, Oxford, UK.
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Zaloum SA, Mair D, Paris A, Smith LJ, Patyjewicz M, Onen BL, Noyce AJ. Tackling the growing burden of nitrous oxide-induced public health harms. Lancet Public Health 2025; 10:e257-e263. [PMID: 39929213 DOI: 10.1016/s2468-2667(24)00298-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2024] [Revised: 11/22/2024] [Accepted: 12/02/2024] [Indexed: 03/08/2025]
Abstract
Nitrous oxide has been increasing in popularity as a recreational drug in the past decade, and with this an increase in health harms related to nitrous oxide use, particularly nitrous oxide-induced myeloneuropathy. In response, governments in many countries have adopted new laws that either target the end user, by criminalising possession, or target suppliers. The effect of these measures remains to be seen, but the potential to exacerbate harm by targeting the user and thus affecting health-care-seeking behaviour is a concern. Education around the preventable harm from recreational use of nitrous oxide and tightening regulations on suppliers are essential in mitigating the increase in nitrous oxide-related health harms.
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Affiliation(s)
- Safiya A Zaloum
- Centre for Preventive Neurology, Wolfson Institute of Population Health, Queen Mary University of London, London, UK
| | - Devan Mair
- Centre for Preventive Neurology, Wolfson Institute of Population Health, Queen Mary University of London, London, UK
| | - Alvar Paris
- Centre for Preventive Neurology, Wolfson Institute of Population Health, Queen Mary University of London, London, UK; Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK
| | - Laura J Smith
- Centre for Preventive Neurology, Wolfson Institute of Population Health, Queen Mary University of London, London, UK
| | - Marta Patyjewicz
- Centre for Preventive Neurology, Wolfson Institute of Population Health, Queen Mary University of London, London, UK; Barts Health NHS Trust, London, UK
| | | | - Alastair J Noyce
- Centre for Preventive Neurology, Wolfson Institute of Population Health, Queen Mary University of London, London, UK; Barts Health NHS Trust, London, UK.
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Wang Z, Zhou L, Wang F, Jiang X, Wang W, Qiu X, Xing Y, Fu C, Zhong P, Tang L. Nitrous oxide analgesia for rehabilitation after anterior cruciate ligament reconstruction: A randomized controlled trial. Ann Phys Rehabil Med 2025; 68:101897. [PMID: 39798171 DOI: 10.1016/j.rehab.2024.101897] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2023] [Revised: 06/10/2024] [Accepted: 07/10/2024] [Indexed: 01/15/2025]
Abstract
BACKGROUND Although there is increasing emphasis on rehabilitation training after ligament reconstruction, little is known about the pain induced by the procedure itself. Procedural success may be limited by pain and anxiety. Nitrous oxide is widely used to alleviate procedural pain. However, few studies have been conducted to show the efficacy and safety of nitrous oxide for rehabilitation training. OBJECTIVES To explore the short-term efficacy and safety of nitrous oxide for acute pain elicited by rehabilitation training. METHODS A double-blinded randomized placebo-controlled trial was conducted in the department of rehabilitation medicine. People willing to participate in the trial and sign informed consent, ≥18 years old, who had acute pain (self-reported pain score ≥4) caused by rehabilitation training after anterior cruciate ligament reconstruction were recruited. Participants undergoing rehabilitation training were randomized to receive either 65 % nitrous oxide or 100 % oxygen. The primary outcome was the pain score. Secondary outcomes were sedation score, range of motion, vital signs, physician and participant satisfaction, acceptance, and side effects. RESULTS 120 people were enrolled; 60 received nitrous oxide and 60 received oxygen. The nitrous oxide group had a significantly lower pain score than the placebo group (P < 0.001, median difference -3, 95 % CI -4 to -2, effect size η2 = 0.369) and sedation scores (P < 0.001, median difference 1, 95 % CI 1 to 1, η2 = 0.263) during the procedure. Both physician (P < 0.001) and participant (P < 0.001) satisfaction were significantly higher in the intervention group than the placebo group. Acceptance (willingness to use the same gas next time) differed between groups (P < 0.001). No serious side effects occurred. CONCLUSION This study provides evidence supporting the efficacy and safety of self-administered nitrous oxide to reduce procedural pain during rehabilitation training after anterior cruciate ligament reconstruction.
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Affiliation(s)
- Ziyang Wang
- Department of Stomatology, The 960th Hospital of People's Liberation Army of China (PLA), Jinan, Shandong, 250031, China; School of Nursing, Shandong Second Medical University, Weifang, Shandong, 261053, China
| | - Lingjun Zhou
- School of Nursing, Naval Military Medical University, Shanghai, 571623, China
| | - Fei Wang
- Department of Anesthesiology, The 960th Hospital of People's Liberation Army of China (PLA), Jinan, Shandong, 250031, China
| | - Xiaochen Jiang
- Department of Stomatology, The 960th Hospital of People's Liberation Army of China (PLA), Jinan, Shandong, 250031, China; School of Nursing, Shandong Second Medical University, Weifang, Shandong, 261053, China
| | - Weifeng Wang
- Department of Stomatology, The 960th Hospital of People's Liberation Army of China (PLA), Jinan, Shandong, 250031, China; School of Nursing, Shandong Second Medical University, Weifang, Shandong, 261053, China
| | - Xueling Qiu
- Department of Stomatology, The 960th Hospital of People's Liberation Army of China (PLA), Jinan, Shandong, 250031, China; School of Nursing, Shandong First Medical University, Taian, 271016, China
| | - Yihui Xing
- Department of Outpatient Comprehensive Management, Qingdao Stomatological Hospital, Qingdao, 266001, China
| | - Chongjian Fu
- Department of Stomatology, The 960th Hospital of People's Liberation Army of China (PLA), Jinan, Shandong, 250031, China
| | - Ping Zhong
- Department of rehabilitation medicine, The 960th Hospital of People' s Liberation Army of China (PLA), Jinan, 250031, China
| | - Lu Tang
- Department of Stomatology, The 960th Hospital of People's Liberation Army of China (PLA), Jinan, Shandong, 250031, China.
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Li WQ, Liu SN, Yang SC, Lin X, Zhang ZJ. Nitrous oxide exerts rewarding effect via regulating D1 receptor and BDNF pathway in ventral tegmental area-nucleus accumbens dopamine circuit. Transl Psychiatry 2025; 15:34. [PMID: 39875366 PMCID: PMC11775255 DOI: 10.1038/s41398-025-03257-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/29/2024] [Revised: 12/09/2024] [Accepted: 01/23/2025] [Indexed: 01/30/2025] Open
Abstract
Recreational use of nitrous oxide (N2O) has risen dramatically over the past decades. This study aimed to examine its rewarding effect and the underlying mechanisms. The exposure of mice to a subanesthetic concentration (20%) of N2O for 30 min for 4 consecutive days paired with N2O in the morning and paired with the air in the afternoon produced apparent rewarding behavior in the conditioned place preference (CPP) paradigm. This was abrogated by microinjection into the nucleus accumbens (NAc) of the dopamine (DA) D1 receptor antagonist SCH23390, but not the D2 antagonist haloperidol. N2O robustly enhanced DAergic neuronal activity of the ventral tegmental area (VTA) and the concentration of DA in the NAc. The repeated N2O exposure also upregulated the expression of brain-derived neurotrophic factor (BDNF) in the VTA and its multiple downstream mediators in the NAc. Conversely, VTA focal knockdown of BDNF and the inhibition of the downstream mediators suppressed the N2O-induced rewarding effect and the DAergic neuronal activity of the VTA. Further, the combined intervention of BDNF knockdown and D1 antagonist significantly inhibited the N2O-induced rewarding effect in mice, which was greater than that of BDNF knockdown alone, but was not significantly different from that of D1 antagonist alone. These results indicate that the rewarding properties of N2O at subanesthetic concentration are associated with its upregulation of the VTA-NAc DA reward pathway probably via mediation of D1 receptor and BDNF/TrkB signaling. Among them, the modulation of BDNF may be the upstream of D1 receptor involved in N2O rewarding effect.
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Affiliation(s)
- Wen-Qi Li
- School of Chinese Medicine, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong, China
| | - Sheng-Nan Liu
- School of Chinese Medicine, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong, China
| | - Si-Chang Yang
- School of Chinese Medicine, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong, China
| | - Xiang Lin
- School of Chinese Medicine, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong, China.
| | - Zhang-Jin Zhang
- School of Chinese Medicine, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong, China.
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Mohamed Yile MEH, Berteau E, Ramdani N, Mouyen T, Ferrier N. Uncommon Thromboembolic Events in Young Adults: A Rare Cause Uncovered. Cureus 2025; 17:e76962. [PMID: 39906426 PMCID: PMC11793925 DOI: 10.7759/cureus.76962] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/05/2025] [Indexed: 02/06/2025] Open
Abstract
Nitrous oxide (N₂O), widely used as a medical anesthetic, has increasingly been misused recreationally, especially among young people, due to its accessibility and perceived safety. However, prolonged use and high doses can cause severe complications, particularly through functional vitamin B12 dysfunction. These complications include neurological impairments, hematologic abnormalities, and thromboembolic events, such as pulmonary embolism. We report the case of a 20-year-old male with a history of chronic nitrous oxide consumption who presented with extensive bilateral lower limb thrombosis, pulmonary embolism, and peripheral neuropathy. Imaging confirmed extensive iliofemoral thrombosis and bilateral pulmonary embolism. The patient was treated with anticoagulation, vitamin B12 supplementation, and other supportive measures. This case highlights the need to raise awareness about the risks of recreational nitrous oxide use and underscores the importance of timely intervention to prevent severe complications.
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Affiliation(s)
| | | | - Nabil Ramdani
- Cardiology, Hospital Center Jacques Lacarin, Vichy, FRA
| | - Thomas Mouyen
- Cardiology, Hospital Center Jacques Lacarin, Vichy, FRA
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Alitalo O, Kohtala S, Rosenholm M, Saarreharju R, González-Hernández G, Sarparanta M, Rozov S, Rantamäki T. Nitrous oxide induces hypothermia and TrkB activation: Maintenance of body temperature abolishes antidepressant-like effects in mice. Neuropharmacology 2024; 261:110172. [PMID: 39362627 DOI: 10.1016/j.neuropharm.2024.110172] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2024] [Revised: 09/24/2024] [Accepted: 09/27/2024] [Indexed: 10/05/2024]
Abstract
Recent studies indicate that nitrous oxide (N2O), a gaseous anesthetic and an NMDA (N-methyl-D-aspartate) receptor antagonist, produces rapid antidepressant effect in patients suffering from treatment-resistant depression. Our recent work implies that hypothermia and reduced energy expenditure are connected with antidepressant-induced activation of TrkB neurotrophin receptors - a key regulator of synaptic plasticity. In this study, we demonstrate that a brief exposure to N2O leads to a drop in body temperature following the treatment, which is linked to decreased locomotor activity; enhanced slow-wave electroencephalographic activity; reduced brain glucose utilization; and increased phosphorylation of TrkB, GSK3β (glycogen synthase kinase 3β), and p70S6K (a kinase downstream of mTor (mammalian target of rapamycin)) in the medial prefrontal cortex of adult male mice. Moreover, preventing the hypothermic response in a chronic corticosterone stress model of depression attenuated the antidepressant-like behavioral effects of N2O in the saccharin preference test. These findings indicate that N2O treatment modulates TrkB signaling and related neurotrophic signaling pathways in a temperature-dependent manner, suggesting that the phenomenon driving TrkB activation - altered thermoregulation and energy expenditure - is linked to antidepressant-like behavioral responses.
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Affiliation(s)
- Okko Alitalo
- Laboratory of Neurotherapeutics, Drug Research Program, Division of Pharmacology and Pharmacotherapy, Faculty of Pharmacy, University of Helsinki, Finland; SleepWell Research Program, Faculty of Medicine, University of Helsinki, Finland
| | - Samuel Kohtala
- Laboratory of Neurotherapeutics, Drug Research Program, Division of Pharmacology and Pharmacotherapy, Faculty of Pharmacy, University of Helsinki, Finland; SleepWell Research Program, Faculty of Medicine, University of Helsinki, Finland
| | - Marko Rosenholm
- Laboratory of Neurotherapeutics, Drug Research Program, Division of Pharmacology and Pharmacotherapy, Faculty of Pharmacy, University of Helsinki, Finland; SleepWell Research Program, Faculty of Medicine, University of Helsinki, Finland; Center for Translational Neuromedicine, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark
| | - Roosa Saarreharju
- Laboratory of Neurotherapeutics, Drug Research Program, Division of Pharmacology and Pharmacotherapy, Faculty of Pharmacy, University of Helsinki, Finland; SleepWell Research Program, Faculty of Medicine, University of Helsinki, Finland
| | - Gemma González-Hernández
- Laboratory of Neurotherapeutics, Drug Research Program, Division of Pharmacology and Pharmacotherapy, Faculty of Pharmacy, University of Helsinki, Finland; SleepWell Research Program, Faculty of Medicine, University of Helsinki, Finland; Neuropsychopharmacology and Psychobiology Research Group, Department of Neurosciences, University of Cádiz, Cádiz, Spain
| | | | - Stanislav Rozov
- Laboratory of Neurotherapeutics, Drug Research Program, Division of Pharmacology and Pharmacotherapy, Faculty of Pharmacy, University of Helsinki, Finland; SleepWell Research Program, Faculty of Medicine, University of Helsinki, Finland
| | - Tomi Rantamäki
- Laboratory of Neurotherapeutics, Drug Research Program, Division of Pharmacology and Pharmacotherapy, Faculty of Pharmacy, University of Helsinki, Finland; SleepWell Research Program, Faculty of Medicine, University of Helsinki, Finland.
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Cichon J, Joseph TT, Lu X, Wasilczuk AZ, Kelz MB, Mennerick SJ, Zorumski CF, Nagele P. Nitrous Oxide activates layer 5 prefrontal neurons via SK2 channel inhibition for antidepressant effect. RESEARCH SQUARE 2024:rs.3.rs-5141491. [PMID: 39606485 PMCID: PMC11601843 DOI: 10.21203/rs.3.rs-5141491/v1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 11/29/2024]
Abstract
Nitrous oxide (N2O) induces rapid and durable antidepressant effects. The cellular and circuit mechanisms mediating this process are not known. Here we find that a single dose of inhaled N2O induces rapid and specific activation of layer V (L5) pyramidal neurons in the cingulate cortex of rodents exposed to chronic stress conditions. N2O-induced L5 activation rescues a stress-associated hypoactivity state, persists following exposure, and is necessary for its antidepressant-like activity. Although NMDA-receptor antagonism is believed to be a primary mechanism of action for N2O, L5 neurons activate even when NMDA-receptor function is attenuated through both pharmacological and genetic approaches. By examining different molecular and circuit targets, we identify N2O-induced inhibition of calcium-sensitive potassium (SK2) channels as a key molecular interaction responsible for driving specific L5 activity along with ensuing antidepressant-like effects. These results suggest that N2O-induced L5 activation is crucial for its fast antidepressant action and this effect involves novel and specific molecular actions in distinct cortical cell types.
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Affiliation(s)
- Joseph Cichon
- Department of Anesthesiology and Critical Care, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
- Mahoney Institute for Neurosciences, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
| | - Thomas T. Joseph
- Department of Anesthesiology and Critical Care, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
| | - Xinguo Lu
- Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA
- The Taylor Family Institute for Innovative Psychiatric Research, Washington University School of Medicine
| | - Andrzej Z. Wasilczuk
- Department of Anesthesiology and Critical Care, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
| | - Max B. Kelz
- Department of Anesthesiology and Critical Care, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
- Mahoney Institute for Neurosciences, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
| | - Steven J. Mennerick
- Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA
- The Taylor Family Institute for Innovative Psychiatric Research, Washington University School of Medicine
| | - Charles F. Zorumski
- Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA
- The Taylor Family Institute for Innovative Psychiatric Research, Washington University School of Medicine
| | - Peter Nagele
- Department of Anesthesia and Critical Care, University of Chicago, Chicago, Illinois
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11
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Wang Z, Wang F, Jiang X, Wang W, Xing Y, Qiu X, Sun C, Tang L. Nitrous Oxide to Reduce Wound Care-Related Pain in Adults: A Systematic Review and Meta-Analysis. Adv Wound Care (New Rochelle) 2024; 13:542-552. [PMID: 38511513 DOI: 10.1089/wound.2023.0211] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/22/2024] Open
Abstract
Significance: As an essential procedure, wound care comes with acute pain, which is short but high in intensity, causing patients to fear and affecting subsequent treatment. Nitrous oxide (N2O) is used to relieve pain related to wound care; however, evidence regarding its application is conflicting. Thus, this systematic review and meta-analysis was performed to evaluate the efficacy of N2O in wound care-related pain. Recent Advances: Randomized controlled trials that investigated the effect of N2O in adults undergoing wound care were systematically searched from PubMed, Embase, the Cochrane Library, Web of Science, Scopus, and ClinicalTrials.gov up to February 2023. The primary outcome was the pain score. Secondary outcomes included patients' satisfaction and side effects. Critical Issues: Through screening the 265 identified articles, seven and six studies were finally included in the systematic review and meta-analysis, respectively. Pooled analysis suggested that there was no significant difference in reducing wound care-related pain between the N2O group and the control group (mean difference [MD], -0.02, 95% confidence interval [CI], -1.46, 1.42; p = 0.98, I2 = 96%). Subgroup analyses indicated that there was a significant difference in favor of N2O for burns, not for ulcers, and N2O was superior to oxygen and similar to topical or intravenous anesthesia. There was no significant difference in patients' satisfaction or the incidence of side effects between groups. Future Directions: This review suggests that N2O might be effective for pain management in patients undergoing wound care. Caution must be taken when interpreting these results due to the high risk of biased methods in the included studies.
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Affiliation(s)
- Ziyang Wang
- Department of Stomatology, The 960th Hospital of People' s Liberation Army of China (PLA), Jinan, People's Republic of China
- School of Nursing, Weifang Medical University, Weifang, People's Republic of China
| | - Fei Wang
- Department of Anesthesiology, The 960th Hospital of People's Liberation Army of China (PLA), Jinan, People's Republic of China
| | - Xiaochen Jiang
- Department of Stomatology, The 960th Hospital of People' s Liberation Army of China (PLA), Jinan, People's Republic of China
- School of Nursing, Weifang Medical University, Weifang, People's Republic of China
| | - Weifeng Wang
- Department of Stomatology, The 960th Hospital of People' s Liberation Army of China (PLA), Jinan, People's Republic of China
- School of Nursing, Weifang Medical University, Weifang, People's Republic of China
| | - Yihui Xing
- Department of Stomatology, The 960th Hospital of People' s Liberation Army of China (PLA), Jinan, People's Republic of China
- School of Nursing, Weifang Medical University, Weifang, People's Republic of China
| | - Xueling Qiu
- Department of Stomatology, The 960th Hospital of People' s Liberation Army of China (PLA), Jinan, People's Republic of China
- School of Nursing, Shandong First Medical University, Tai'an, People's Republic of China
| | - Chenxi Sun
- Department of Stomatology, The 960th Hospital of People' s Liberation Army of China (PLA), Jinan, People's Republic of China
- Graduate Training Base of Jinzhou Medical University, The 960th Hospital of People's Liberation Army of China, Jinzhou, People's Republic of China
| | - Lu Tang
- Department of Stomatology, The 960th Hospital of People' s Liberation Army of China (PLA), Jinan, People's Republic of China
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12
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Tran CJ, Campbell TL, Johnson RH, Xie LY, Hultman CM, van den Oord EJCG, Aberg KA. Cell-type specific methylation changes in the newborn child associated to obstetric pain relief. PLoS One 2024; 19:e0308644. [PMID: 39298419 DOI: 10.1371/journal.pone.0308644] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2024] [Accepted: 07/28/2024] [Indexed: 09/21/2024] Open
Abstract
Although it is widely known that various pharmaceuticals affect the methylome, the knowledge of the effects from anesthesia is limited, and nearly nonexistent regarding the effects of obstetric anesthesia on the newborn child. Using sequencing based-methylation data and a reference-based statistical deconvolution approach we performed methylome-wide association studies (MWAS) of neonatal whole blood, and for each cell-type specifically, to detect methylation variations that are associated with the pain relief administered to the mother during delivery. Significant findings were replicated in a different dataset and followed-up with gene ontology analysis to pinpoint biological functions of potential relevance to these neonatal methylation alterations. The MWAS analyses detected methylome-wide significant (q<0.1) alterations in the newborn for laughing gas in granulocytes (two CpGs, p<5.50x10-9, q = 0.067), and for pudendal block in monocytes (five CpGs across three loci, p<1.51 x10-8, q = 0.073). Suggestively significant findings (p<1.00x10-6) were detected for both treatments for bulk and all cell-types, and replication analyses showed consistent significant enrichment (odds ratios ranging 3.47-39.02; p<4.00×10-4) for each treatment, suggesting our results are robust. In contrast, we did not observe any overlap across treatments, suggesting that the treatments are associated with different alterations of the neonatal blood methylome. Gene ontology analyses of the replicating suggestively significant results indicated functions related to, for example, cell differentiation, intracellular membrane-bound organelles and calcium transport. In conclusion, for the first time, we investigated and detected effect of obstetric pain-relief on the blood methylome in the newborn child. The observed differences suggest that anesthetic treatment, such as laughing gas or pudendal block, may alter the neonatal methylome in a cell-type specific manner. Some of the observed alterations are part of gene ontology terms that previously have been suggested in relation to anesthetic treatment, supporting its potential role also in obstetric anesthesia.
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Affiliation(s)
- Charles J Tran
- Center for Biomarker Research and Precision Medicine, Virginia Commonwealth University, Richmond, VA, United States of America
| | - Thomas L Campbell
- Center for Biomarker Research and Precision Medicine, Virginia Commonwealth University, Richmond, VA, United States of America
| | - Ralen H Johnson
- Center for Biomarker Research and Precision Medicine, Virginia Commonwealth University, Richmond, VA, United States of America
| | - Lin Y Xie
- Center for Biomarker Research and Precision Medicine, Virginia Commonwealth University, Richmond, VA, United States of America
| | - Christina M Hultman
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
| | - Edwin J C G van den Oord
- Center for Biomarker Research and Precision Medicine, Virginia Commonwealth University, Richmond, VA, United States of America
| | - Karolina A Aberg
- Center for Biomarker Research and Precision Medicine, Virginia Commonwealth University, Richmond, VA, United States of America
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13
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Nguyen N, Cao J, Carlson D, Kong L, Diaz G. Nitrous Oxide Use Precipitates Pulmonary Embolism: A Case Report. Cureus 2024; 16:e69347. [PMID: 39282482 PMCID: PMC11398614 DOI: 10.7759/cureus.69347] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/12/2024] [Indexed: 09/19/2024] Open
Abstract
Nitrous oxide (N2O) has a lengthy history of use as an anesthetic and has recently found popularity as a recreational euphoric hallucinogen. The odorless, colorless, non-flammable gas interferes with Vitamin B12 resulting in a cascade of effects, including hyperhomocysteinemia. It has long been proposed that hyperhomocysteinemia adversely affects the cardiovascular system, producing atherogenic and prothrombotic diseases. In this case vignette, we describe a case in which a healthy patient presented with venous thromboembolism (VTE) that we suspect could have been precipitated by daily and significant recreational use of N2O. Anticoagulation therapy was given, and there was a significant improvement in the pulmonary emboli. As recreational use of N2O increases, it is essential to recognize that hyperhomocysteinemia may also produce a thrombotic state.
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Affiliation(s)
- Nancy Nguyen
- Medicine, Community Memorial Health Systems, Ventura, USA
- Medicine, Western University of Health Sciences, Pomona, USA
| | - Jessica Cao
- General Surgery, Community Memorial Hospital, Ventura, USA
| | - Deborah Carlson
- Graduate Medical Education / Internal Medicine, Community Memorial Hospital, Ventura, USA
| | - Lynn Kong
- Department of Oncology, Ventura Cancer Center, Ventura, USA
| | - Graal Diaz
- Graduate Medical Education, Community Memorial Hospital, Ventura, USA
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14
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Wehrman JJ, Chung CC, Sanders R. Anaesthetics and time perception: A review. Q J Exp Psychol (Hove) 2024; 77:1898-1910. [PMID: 36453756 DOI: 10.1177/17470218221144614] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/02/2022]
Abstract
Consciousness requires subjective experience in the "now." Establishing "now," however, necessitates temporal processing. In the current article, we review one method of altering consciousness, anaesthetic drug administration, and its effects on perceived duration. We searched PubMed, PsycInfo, and ScienceDirect databases, and article reference sections, for combinations of anaesthetic drugs and time perception tasks, finding a total of 36 articles which met our inclusion criteria. We categorised these articles with regard to whether they altered the felt passage of time, short or long interval timing, or were motor timing tasks. We found that various drugs alter the perceived passage of time; ketamine makes time subjectively slow down while GABAergic drugs make time subjectively speed up. At a short interval there is little established evidence of a shift in time perception, though temporal estimates appear more variable. Similarly, when asked to use time to optimise responses (i.e., in motor timing tasks), various anaesthetic agents make timing more variable. Longer durations are estimated as lasting longer than their objective duration, though there is some variation across articles in this regard. We conclude by proposing further experiments to examine time perception under altered states of consciousness and ask whether it is possible to perceive the passage of time of events which do not necessarily reach the level of conscious perception. The variety of methods used raises the need for more systematic investigations of time perception under anaesthesia. We encourage future investigations into the overlap of consciousness and time perception to advance both fields.
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Affiliation(s)
| | - Clara C Chung
- Royal Prince Alfred Hospital, Sydney, NSW, Australia
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15
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Pruski M. AI-Enhanced Healthcare: Not a new Paradigm for Informed Consent. JOURNAL OF BIOETHICAL INQUIRY 2024; 21:475-489. [PMID: 38300443 PMCID: PMC11652578 DOI: 10.1007/s11673-023-10320-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/28/2022] [Accepted: 11/06/2023] [Indexed: 02/02/2024]
Abstract
With the increasing prevalence of artificial intelligence (AI) and other digital technologies in healthcare, the ethical debate surrounding their adoption is becoming more prominent. Here I consider the issue of gaining informed patient consent to AI-enhanced care from the vantage point of the United Kingdom's National Health Service setting. I build my discussion around two claims from the World Health Organization: that healthcare services should not be denied to individuals who refuse AI-enhanced care and that there is no precedence to seeking patient consent to AI-enhanced care. I discus U.K. law relating to patient consent and the General Data Protection Regulation to show that current standards relating to patient consent are adequate for AI-enhanced care. I then suggest that in the future it may not be possible to guarantee patient access to non-AI-enhanced healthcare, in a similar way to how we do not offer patients manual alternatives to automated healthcare processes. Throughout my discussion I focus on the issues of patient choice and veracity in the patient-clinician relationship. Finally, I suggest that the best way to protect patients from potential harms associated with the introduction of AI to patient care is not via an overly burdensome patient consent process but via evaluation and regulation of AI technologies.
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Affiliation(s)
- M Pruski
- School of Health Sciences, The University of Manchester, Manchester, UK.
- Department of Medical Physics and Clinical Engineering, Cardiff and Vale University Health Board, Cardiff, Wales, UK.
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16
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Rao AK, Syed F, Lee TJ, Umanzor GU, Bodle J. Falling From Laughing: Laughing Gas-Induced Subacute Combined Degeneration From Nitrous Oxide. Cureus 2024; 16:e62138. [PMID: 38993425 PMCID: PMC11238261 DOI: 10.7759/cureus.62138] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/11/2024] [Indexed: 07/13/2024] Open
Abstract
Laughing gas is becoming increasingly popular as a recreational drug of choice, particularly among young adults. Nitrous oxide, the toxic component of laughing gas, can cause neuronal injury when used in high doses. Through multiple mechanisms, nitrous oxide leads to B12 depletion and subsequent demyelination, particularly in the spinal cord. Here, we present the case of a 27-year-old female who presented with ataxia and was found to have laughing gas-induced subacute combined degeneration from nitrous oxide. After aggressive vitamin B12 repletion and laughing gas cessation for three months, the patient improved.
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Affiliation(s)
- Abhinav K Rao
- Internal Medicine, Trident Medical Center, Charleston, USA
| | - Fahim Syed
- Internal Medicine, Trident Medical Center, Charleston, USA
| | - Thomas J Lee
- Internal Medicine, Rutgers University New Jersey Medical School, Newark, USA
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17
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Victorri-Vigneau C, Grall Bronnec M. Yes, nitrous oxide addiction undeniably exists! Addiction 2024; 119:625-626. [PMID: 38196069 DOI: 10.1111/add.16430] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/12/2023] [Accepted: 12/18/2023] [Indexed: 01/11/2024]
Affiliation(s)
- Caroline Victorri-Vigneau
- Nantes Université, CHU Nantes - Service de pharmacologie clinique - Centre d'Evaluation et d'Information sur la Pharmacodependence - Addictovigilance (CEIP-A), Nantes, France
- INSERM UMR1246, SPHERE methodS in Patients-centered outcomes and Health REsearch, Université de Nantes et de Tours, Nantes, France
| | - Marie Grall Bronnec
- INSERM UMR1246, SPHERE methodS in Patients-centered outcomes and Health REsearch, Université de Nantes et de Tours, Nantes, France
- Nantes université, CHU Nantes, Service d'Addictologie et de Psychiatrie de liaison, Nantes, France
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18
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Dupeyron A, Dobija L, Castelli C, Petiot S, Tavares I, Gélis A, Coudeyre E. Nitrous oxide provided during intensive physiotherapy for shoulder adhesive capsulitis does not improve function: A randomised controlled trial. Ann Phys Rehabil Med 2024; 67:101803. [PMID: 38118247 DOI: 10.1016/j.rehab.2023.101803] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2021] [Revised: 07/22/2023] [Accepted: 10/05/2023] [Indexed: 12/22/2023]
Abstract
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.
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Affiliation(s)
- Arnaud Dupeyron
- Department of Physical Medicine and Rehabilitation, CHU Nîmes, Univ Montpellier, Nîmes, France; EuroMov Digital Health in Motion, Univ Montpellier, IMT Mines Ales, Montpellier, France.
| | - Lech Dobija
- Department of Physical Medicine and Rehabilitation, CHRU de Clermont-Ferrand Université Clermont Auvergne, France
| | - Christel Castelli
- Department of Biostatistics, Epidemiology, Public Health and Innovation in Methodology (BESPIM), CHU Nîmes, Univ Montpellier, Nîmes, France
| | - Sylvie Petiot
- Department of Physical Medicine and Rehabilitation, CHU Nîmes, Univ Montpellier, Le Grau du Roi, France
| | - Isabelle Tavares
- Department of Physical Medicine and Rehabilitation, CHRU Lapeyronie, Univ Montpellier, Montpellier, France
| | - Anthony Gélis
- Propara Neurologic Rehabilitation Centre, Parc Euromédecine, Montpellier, France
| | - Emmanuel Coudeyre
- Department of Physical Medicine and Rehabilitation, CHRU de Clermont-Ferrand Université Clermont Auvergne, France; INRA, Unité de Nutrition Humaine (UNH, UMR 1019), CRNH Auvergne, Clermont-Ferrand, France
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19
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Back S, Kroon E, Colyer-Patel K, Cousijn J. Does nitrous oxide addiction exist? An evaluation of the evidence for the presence and prevalence of substance use disorder symptoms in recreational nitrous oxide users. Addiction 2024; 119:609-618. [PMID: 37904333 DOI: 10.1111/add.16380] [Citation(s) in RCA: 11] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/14/2023] [Accepted: 10/03/2023] [Indexed: 11/01/2023]
Abstract
BACKGROUND Prevalence of nitrous oxide (N2 O) use appears to be increasing in numerous countries worldwide, and excessive use has been associated with physical and mental problems. Because there currently is no consensus whether N2 O has addictive potential, we aimed to evaluate the evidence for the presence and prevalence of DSM-5 substance use disorder (SUD) symptoms in N2 O users. ANALYSIS A literature search was conducted to assess the evidence for the presence of any of the 11 DSM-5 SUD symptoms in N2 O users and the prevalence experiencing those symptoms. A substantial part of the studied N2 O users use more than intended (i.e. 46% to 98%) and spend a substantial amount of time using N2 O. At least some of the studied N2 O users experience interpersonal problems (i.e. 13% to 80%) and use N2 O in risky situations, such as driving under the influence. Evidence for the other criteria is either insufficient or inconclusive. CONCLUSIONS The literature base for the presence and prevalence of DSM-5 substance use disorder (SUD) symptoms in nitrous oxide (N2 O) users is limited and largely consists of qualitative studies and case studies, but it provides consistent evidence for the presence of at least four SUD criteria in heavy N2 O users. N2 O could well be addictive and should be treated as a potentially addictive substance until systematic assessments can provide evidence-based guidance to users, healthcare professionals and legislators.
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Affiliation(s)
- Sammie Back
- Neuroscience of Addiction (NofA) Lab, Center for Substance use and Addiction Research (CESAR), Department of Psychology, Education and Child Studies, Erasmus University Rotterdam, Rotterdam, The Netherlands
| | - Emese Kroon
- Neuroscience of Addiction (NofA) Lab, Center for Substance use and Addiction Research (CESAR), Department of Psychology, Education and Child Studies, Erasmus University Rotterdam, Rotterdam, The Netherlands
- Department of Psychology, University of Amsterdam, Amsterdam, The Netherlands
| | - Karis Colyer-Patel
- Neuroscience of Addiction (NofA) Lab, Center for Substance use and Addiction Research (CESAR), Department of Psychology, Education and Child Studies, Erasmus University Rotterdam, Rotterdam, The Netherlands
| | - Janna Cousijn
- Neuroscience of Addiction (NofA) Lab, Center for Substance use and Addiction Research (CESAR), Department of Psychology, Education and Child Studies, Erasmus University Rotterdam, Rotterdam, The Netherlands
- Department of Psychology, University of Amsterdam, Amsterdam, The Netherlands
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20
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Gérardin M, Rousselet M, Couec ML, Masseau A, Aquizerate A, Authier N, Deheul S, Roussin A, Micallef J, Djezzar S, Feuillet F, Jolliet P, Grall-Bronnec M, Victorri-Vigneau C. Substance use disorder of equimolar oxygen-nitrous oxide mixture in French sickle-cell patients: results of the PHEDRE study. Orphanet J Rare Dis 2024; 19:124. [PMID: 38500184 PMCID: PMC10949610 DOI: 10.1186/s13023-024-03133-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2023] [Accepted: 03/03/2024] [Indexed: 03/20/2024] Open
Abstract
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/.
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Affiliation(s)
- Marie Gérardin
- CHU Nantes, Centre d'Evaluation et d'Information sur la Pharmacodépendance-Addictovigilance (CEIP-A), Service de Pharmacologie Clinique, Nantes Université, 9 Quai Moncousu, 44 093, Nantes Cedex 1, France
| | - Morgane Rousselet
- CHU Nantes, Centre d'Evaluation et d'Information sur la Pharmacodépendance-Addictovigilance (CEIP-A), Service de Pharmacologie Clinique, Nantes Université, 9 Quai Moncousu, 44 093, Nantes Cedex 1, France
- CHU Nantes, UIC Psychiatrie et Santé Mentale, Nantes Université, Nantes, France
- CHU Nantes, CHU Tours, INSERM, MethodS in Patients Centered Outcomes and HEalth ResEarch, SPHERE, Nantes Université, Tours Université, Nantes, France
| | - Marie-Laure Couec
- CHU Nantes, Service de Pédiatrie et d'Oncologie Pédiatrique, Nantes Université, Nantes, France
| | - Agathe Masseau
- CHU Nantes, Service de Médecine Interne, Nantes Université, Nantes, France
| | - Aurélie Aquizerate
- CHU Nantes, Centre d'Evaluation et d'Information sur la Pharmacodépendance-Addictovigilance (CEIP-A), Service de Pharmacologie Clinique, Nantes Université, 9 Quai Moncousu, 44 093, Nantes Cedex 1, France
| | - Nicolas Authier
- CHU Clermont-Ferrand, Service de Pharmacologie Médicale, Clermont Auvergne Université, Clermont-Ferrand, France
| | - Sylvie Deheul
- CHU Lille, Service de Pharmacologie, Lille Université, Lille, France
| | - Anne Roussin
- CHU Toulouse, Service de Pharmacologie Médicale et Clinique, Toulouse Université, Toulouse, France
| | - Joelle Micallef
- APHM, Service de Pharmacologie Clinique, Hôpital de La Timone, Institut de Neurosciences Des Systèmes, Aix-Marseille Université, Marseille, France
| | - Samira Djezzar
- APHP Paris, Centre d'Evaluation et d'Information sur la Pharmacodependence-Addictovigilance de Paris, Hôpital Fernand Widal, APHP Paris, Paris, France
| | - Fanny Feuillet
- CHU Nantes, CHU Tours, INSERM, MethodS in Patients Centered Outcomes and HEalth ResEarch, SPHERE, Nantes Université, Tours Université, Nantes, France
- CHU Nantes, DRI, Plateforme de Méthodologie et Biostatistique, Nantes Université, Nantes, France
| | - Pascale Jolliet
- CHU Nantes, Centre d'Evaluation et d'Information sur la Pharmacodépendance-Addictovigilance (CEIP-A), Service de Pharmacologie Clinique, Nantes Université, 9 Quai Moncousu, 44 093, Nantes Cedex 1, France
- CHU Nantes, CHU Tours, INSERM, MethodS in Patients Centered Outcomes and HEalth ResEarch, SPHERE, Nantes Université, Tours Université, Nantes, France
| | - Marie Grall-Bronnec
- CHU Nantes, UIC Psychiatrie et Santé Mentale, Nantes Université, Nantes, France
- CHU Nantes, CHU Tours, INSERM, MethodS in Patients Centered Outcomes and HEalth ResEarch, SPHERE, Nantes Université, Tours Université, Nantes, France
| | - Caroline Victorri-Vigneau
- CHU Nantes, Centre d'Evaluation et d'Information sur la Pharmacodépendance-Addictovigilance (CEIP-A), Service de Pharmacologie Clinique, Nantes Université, 9 Quai Moncousu, 44 093, Nantes Cedex 1, France.
- CHU Nantes, CHU Tours, INSERM, MethodS in Patients Centered Outcomes and HEalth ResEarch, SPHERE, Nantes Université, Tours Université, Nantes, France.
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21
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Allen E, Whitehouse K. Is there a future for nitrous oxide in anaesthetic practice? Br J Hosp Med (Lond) 2024; 85:1-2. [PMID: 38557090 DOI: 10.12968/hmed.2023.0280] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/04/2024]
Abstract
Although nitrous oxide is widely used for analgesia and anxiolysis, its use is under scrutiny because of concerns about its environmental impact and potential implications for mental health. This article discusses the advantages and disadvantages of this agent.
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Affiliation(s)
- Emma Allen
- Department of Anaesthesia, Royal Victoria Infirmary, Newcastle Upon Tyne, UK
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22
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Suponeva NA, Arestova AS. [Neurological complications resulting of nitrous oxide intoxication]. Zh Nevrol Psikhiatr Im S S Korsakova 2024; 124:41-46. [PMID: 39731369 DOI: 10.17116/jnevro202412412141] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2024]
Abstract
Nitrous oxide (NO) intoxication is a common consequence of its inhalation with recreational purpose, which is prevalent among young people. The most severe result of such an entertainment is development of myelopolyneuropathy with polyneuropathy as the most common presentation, which may start acutely or subacutely. The underlying cause of neurological complications of NO intoxication is deficit of B12 vitamin, however its laboratory confirmation may be challenging. The key aspect of treatment of neurological symptoms in such patients is prescription of adequate dosage of B12 for a long period of time. In this paper we present the clinical case, which demonstrates challenges of vitamin B12 deficiency verification and advantages of oral cyanocobalamin prescription.
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Jain R, Hudson S, Osmond MH, Trottier ED, Poonai N, Ali S. Nitrous oxide use in Canadian pediatric emergency departments: a survey of physician's knowledge, attitudes, and practices. CAN J EMERG MED 2024; 26:47-56. [PMID: 37855985 DOI: 10.1007/s43678-023-00602-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2023] [Accepted: 09/24/2023] [Indexed: 10/20/2023]
Abstract
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.
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Affiliation(s)
- Rini Jain
- Faculty of Medicine, Department of Pediatrics, University of Ottawa, Ottawa, Ontario, Canada.
- Children's Hospital of Eastern Ontario, Ottawa, Ontario, Canada.
- Faculty of Medicine, Department of Pediatrics, Division of Emergency Medicine, Jim Pattison Children's Hospital, University of Saskatchewan, Saskatoon, Saskatchewan, Canada.
| | - Summer Hudson
- Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada
| | - Martin H Osmond
- Faculty of Medicine, Department of Pediatrics, University of Ottawa, Ottawa, Ontario, Canada
- Children's Hospital of Eastern Ontario, Ottawa, Ontario, Canada
| | - Evelyne D Trottier
- Department of Pediatrics, CHU Sainte-Justine, Université de Montréal, Montreal, Quebec, Canada
| | - Naveen Poonai
- Departments of Pediatrics, Internal Medicine, Epidemiology and Biostatistics, Western University, London, Ontario, Canada
| | - Samina Ali
- Faculty of Medicine and Dentistry, Department of Pediatrics, University of Alberta, Edmonton, Alberta, Canada
- Women and Children's Health Research Institute, Edmonton, Alberta, Canada
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Davidson LT. Recreational use of nitrous oxide causes seizure, pneumothorax, pneumomediastinum, and pneumopericardium: nitrous oxide and its harm, a case report. Ups J Med Sci 2023; 128:10281. [PMID: 38084205 PMCID: PMC10710853 DOI: 10.48101/ujms.v128.10281] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/05/2023] [Revised: 11/08/2023] [Accepted: 11/13/2023] [Indexed: 12/18/2023] Open
Abstract
Nitrous oxide, commonly known as 'laughing gas', has become a popular recreational drug. Whippets, small canisters containing gas in pressurized form, can be easily obtained from a food store. However, inhaling nitrous oxide from these canisters, which contain a 100% concentration, can lead to hypoxia, resulting in seizures or even death. Inhalation of nitrous oxide rarely causes pneumothorax, pneumomediastinum, and pneumopericardium. This case study highlights the potential dangers of recreational abuse of nitrous oxide.
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Affiliation(s)
- Lee Ti Davidson
- Department of Emergency Medicine, Linköping University, Linköping, Sweden
- Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden
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Gernez E, Lee GR, Niguet JP, Zerimech F, Bennis A, Grzych G. Nitrous Oxide Abuse: Clinical Outcomes, Pharmacology, Pharmacokinetics, Toxicity and Impact on Metabolism. TOXICS 2023; 11:962. [PMID: 38133363 PMCID: PMC10747624 DOI: 10.3390/toxics11120962] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/27/2023] [Revised: 11/22/2023] [Accepted: 11/26/2023] [Indexed: 12/23/2023]
Abstract
The recreational use of nitrous oxide (N2O), also called laughing gas, has increased significantly in recent years. In 2022, the European Monitoring Centre for Drugs and Drug Addiction (EMCDDA) recognized it as one of the most prevalent psychoactive substances used in Europe. Chronic nitrous oxide (N2O) exposure can lead to various clinical manifestations. The most frequent symptoms are neurological (sensitive or motor disorders), but there are also other manifestations like psychiatric manifestations or cardiovascular disorders (thrombosis events). N2O also affects various neurotransmitter systems, leading to its anesthetic, analgesic, anxiolytic and antidepressant properties. N2O is very challenging to measure in biological matrices. Thus, in cases of N2O intoxication, indirect biomarkers such as vitamin B12, plasma homocysteine and plasma MMA should be explored for diagnosis and assessment. Others markers, like oxidative stress markers, could be promising but need to be further investigated.
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Affiliation(s)
- Emeline Gernez
- CHU de Lille, Centre de Biologie Pathologie Génétique, 59000 Lille, France; (E.G.); (F.Z.)
| | | | - Jean-Paul Niguet
- Service de Neurologie, Hôpital Saint Vincent de Paul–GHICL, 59000 Lille, France;
| | - Farid Zerimech
- CHU de Lille, Centre de Biologie Pathologie Génétique, 59000 Lille, France; (E.G.); (F.Z.)
| | - Anas Bennis
- Assistance Publique—Hôpitaux de Paris, Service de Neurologie, Groupe Hospitalier Universitaire Paris Sud, Hôpital Bicêtre, 94270 Le Kremlin-Bicêtre, France;
| | - Guillaume Grzych
- CHU de Lille, Centre de Biologie Pathologie Génétique, 59000 Lille, France; (E.G.); (F.Z.)
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Šanjug J, Kuna K, Goldštajn MŠ, Dunkić LF, Carek A, Negovetić Vranić D. Relationship between COMT Gene Polymorphism, Anxiety, and Pain Perception during Labour. J Clin Med 2023; 12:6298. [PMID: 37834942 PMCID: PMC10573766 DOI: 10.3390/jcm12196298] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2023] [Revised: 09/22/2023] [Accepted: 09/26/2023] [Indexed: 10/15/2023] Open
Abstract
BACKGROUND The COMT gene polymorphism is associated with neurological and psychiatric disorders and pain perception. The present study investigates the existence of anxiety and pain perception in relation to the COMT (catechol-O-methyltransferase) gene polymorphism in labouring women (during "natural" childbirth) with or without inhaled analgesia. METHODS A total of 181 women who chose vaginal birth were enrolled in this study. To present the difference in pain perception, the parturients were divided into one group (n = 90) that chose labour analgesia with inhaled nitrous oxide (50% nitrous oxide and 50% oxygen) and one group (n = 91) without analgesia. The blood samples were taken during the pregnancy as a part of routine pregnancy controls in the hospital. The COMT gene polymorphism was detected with the PCR technique. The pain perception of parturients was self-evaluated two times according to the VAS (Visual Analogue Scale), and anxiety as a personality trait was determined with the STAI-T (State Trait Anxiety Inventory). Pain perception as well as anxiety were compared according to COMT genotypes. RESULTS In the 181 pregnant women, there were 40 women (22%) of wild homozygotes (GG) of COMT, 95 women (53%) of mutant heterozygotes (GA), and 46 women (25%) of mutant homozygotes (AA). A negative association of pain perception with the GA (mutant heterozygote) polymorphism of the COMT gene versus the wild-type (GG polymorphism) was observed. The GA polymorphism of the COMT gene was associated with 0.46 units lower pain perception compared to the wild type (GG). The anxiety trait score in group AA was lower than in groups GA and GG. The difference reached statistical significance only when comparing AA versus GA (p > 0.042). Analgesic efficacy of nitrous oxide was noticed in 22% of labouring women who reported moderate pain (VAS score 4-7). CONCLUSIONS The COMT gene polymorphism was associated with pain perception and anxiety among parturients. The COMT gene polymorphism GA was associated with negative pain perception among labouring women. Nitrous oxide showed statistical significance in anxiolytic efficacy during labour in women with mild anxiety as a personality trait. Anxiolytic efficacy of nitrous oxide has shown better efficacy in parturients with the COMT gene polymorphism AA.
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Affiliation(s)
- Jadranka Šanjug
- Department of Gynaecology and Obstetrics, General Hospital Zabok and War Veterans’ Hospital, Bračak 8, 49210 Zabok, Croatia
| | - Krunoslav Kuna
- Department of Gynaecology and Obstetrics, Sestre Milosrdnice University Hospital Centre, 10000 Zagreb, Croatia;
| | - Marina Šprem Goldštajn
- Department of Obstetrics and Gynecology, Clinical Hospital Center Zagreb, 10000 Zagreb, Croatia
| | - Lidija Fumić Dunkić
- Division of Anesthesiology, Intensive Care and Pain Medicine, Sestre Milosrdnice University Hospital Center, 10000 Zagreb, Croatia;
| | - Andreja Carek
- Department of Fixed Prosthodontics, School of Dental Medicine, University of Zagreb, Gunduliceva 5, 10000 Zagreb, Croatia
| | - Dubravka Negovetić Vranić
- Department of Pediatric Dentistry, School of Dental Medicine, University of Zagreb, Gunduliceva 5, 10000 Zagreb, Croatia
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Rowson AC, Yii MX, Tan HB, Prasad J. Recreational nitrous oxide-induced injury to the soft palate. Clin Case Rep 2023; 11:e7858. [PMID: 37649901 PMCID: PMC10462773 DOI: 10.1002/ccr3.7858] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2023] [Revised: 08/07/2023] [Accepted: 08/18/2023] [Indexed: 09/01/2023] Open
Abstract
Frostbite arising from nitrous oxide (N2O) inhalation is rare. As such, there is no consensus on best treatment for these injuries. In all published reports, judicious use of corticosteroids and antibiotics has resulted in positive clinical outcomes; we endorse these agents in our case of a young man with oropharyngeal burns.
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Affiliation(s)
- Antonia C. Rowson
- Alfred Otolaryngology UnitAlfred HealthMelbourneVictoriaAustralia
- The University of Sydney, Stuart Anderson BuildingCamperdownNew South WalesAustralia
| | - Matthew X. Yii
- Alfred Otolaryngology UnitAlfred HealthMelbourneVictoriaAustralia
| | - Hannah B. Tan
- Alfred Otolaryngology UnitAlfred HealthMelbourneVictoriaAustralia
| | - Jessica Prasad
- Alfred Otolaryngology UnitAlfred HealthMelbourneVictoriaAustralia
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Parein G, Bollens B. Nitrous oxide-induced polyneuropathy, pancytopenia and pulmonary embolism: a case report. J Med Case Rep 2023; 17:350. [PMID: 37587485 PMCID: PMC10433604 DOI: 10.1186/s13256-023-04075-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2023] [Accepted: 07/12/2023] [Indexed: 08/18/2023] Open
Abstract
BACKGROUND Nitrous oxide is a medical and household gas that has seen its use drift to recreational purpose among the young population in recent years. Significant neurological, hematological and psychiatric side effects, generally related to an induced functional vitamin B12 deficiency, have been described separately in the literature. CASE REPORT A 22-year-old woman of North African origin experienced an exceptional combination of polyneuropathy, bilateral pulmonary embolism and severe pancytopenia related to vitamin B12 deficiency and hyperhomocysteinemia induced by recreational nitrous oxide use. After treatment with vitamin B12 supplementation and intensive rehabilitative management, the patient progressively regained the ability to walk and her biological parameters gradually returned to normal. The pathophysiological mechanisms related to a decrease in vitamin B12 activity are the reduction of products needed for synthesis of deoxyribonucleic acid, carbohydrate or fatty acids, and the increase of hyperhomocysteinemia. Other mechanisms involving a direct action of N2O are also suspected. CONCLUSION This case report brings elements to support our knowledge about pathological pathway, recovery and prognosis of recreational N2O abuse complications. The general and medical population should be aware to the serious consequences of this type of consumption.
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Affiliation(s)
- Guillaume Parein
- Physical and Rehabilitation Medicine Department, CHU Ambroise Paré, Mons, Wallonie, Belgium.
| | - Benjamin Bollens
- Physical and Rehabilitation Medicine Department, CHU Ambroise Paré, Mons, Wallonie, Belgium
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Abdulla R, Murray A, Seeballuck C, Heffernan A. Top tips for the management of the dentally anxious patient in general practice. Br Dent J 2023; 235:166-169. [PMID: 37563375 DOI: 10.1038/s41415-023-6199-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/12/2023]
Affiliation(s)
- Ranj Abdulla
- DCT 1, Dundee Dental Hospital and Research School, Dundee, UK.
| | - Aisling Murray
- General Dental Practitioner, Navan, Republic of Ireland.
| | - Clement Seeballuck
- Lecturer in Paediatric Dentistry, Dundee Dental Hospital and Research School, Dundee, UK.
| | - Abigail Heffernan
- Consultant in Special Care Dentistry, Dundee Dental Hospital and Research School, Dundee, UK.
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Desyatnikova S, Mangieri L. Nitrous Oxide Improves Tissue Perfusion in Vascular Occlusion Management. PLASTIC AND RECONSTRUCTIVE SURGERY-GLOBAL OPEN 2023; 11:e5154. [PMID: 37496982 PMCID: PMC10368379 DOI: 10.1097/gox.0000000000005154] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2022] [Accepted: 06/15/2023] [Indexed: 07/28/2023]
Abstract
Filler-related vascular occlusion (VO) treatment remains challenging despite established protocols, including high-dose pulsed hyaluronidase injections and ultrasound-guided targeted injections. Managing patients' pain and anxiety during treatment presents additional difficulties. Nitrous oxide (N2O) has been found to be effective for analgesia and anxiolysis in minor procedures, with a 55% reduction in photodynamic therapy pain, and a visual analog scale reduction from 6.6 to 2.9 for aesthetic laser treatment pain. Use of N2O for analgesia, anxiolysis, or improvement of perfusion in VO has not been previously reported. We present two cases of filler-related VO management with high-dose hourly hyaluronidase injections and adjunctive use of self-administered 50% N2O. Pain and anxiety of the treatment were self-reported by the patients. Capillary refill and livedo reticularis were monitored for establishing VO diagnosis and treatment outcome. In both cases, self-administration of N2O led to contemporaneous improvement in skin perfusion. Patients reported decreased anxiety and pain during treatment. Hyaluronidase treatment led to permanent resolution of occlusion symptoms. N2O presents a promising adjunctive treatment option for relief of pain and anxiety, and potentially additional perfusion improvement. Further investigation is necessary to better define N2O's role in treating VO.
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Perez A, Gernandt S, Scolozzi P. The Use of Equimolar Mixtures of Nitrous Oxide and Oxygen in Oral Surgery-A Retrospective Study of Patients in a Swiss University Hospital Setting. J Clin Med 2023; 12:4117. [PMID: 37373810 DOI: 10.3390/jcm12124117] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2023] [Revised: 06/14/2023] [Accepted: 06/16/2023] [Indexed: 06/29/2023] Open
Abstract
PURPOSE The purpose of the study was to evaluate the success of procedural conscious sedation using inhaled equimolar nitrous oxide-oxygen (NOIS-EMONO) in patients undergoing routine dental and oral surgery procedures in a Swiss university hospital setting. MATERIALS AND METHODS The authors conducted a retrospective cohort study of patients that underwent NOIS-supported procedures between 2018 and 2022 at the oral surgery department of the University Hospital of Geneva (HUG), Switzerland. The primary outcome was the measurement of the procedure's success and efficacy as defined by the European Society of Anesthesiology. Secondary objectives included the analysis of the types of treatments performed, their indications, patient behavior, and the patient-clinician satisfaction score. RESULTS 55 patients were included in the study; 85% underwent surgical procedures, and the remaining 15% underwent restorative and preventive procedures. The overall treatment success rate was 98.2% and 97.9% for surgically treated patients. Out of the patients, 62% appeared relaxed, calm, and serene, while 16% expressed pain or fear during the procedure. Infiltrative administration of local anesthesia caused stress in 22% of patients. This portion was significantly lower in sub-cohorts who received local topical anesthetics (0%) or a combination of systemic and local topical analgesics (7%). Patients (75%) and clinicians (91%) were satisfied with the procedure. CONCLUSION Inhaled equimolar nitrous oxide-oxygen procedural sedation used during dental procedures and oral surgery results in high treatment success and satisfaction rates. The administration of additional topical anesthetics helps to reduce the anxiety and stress related to infiltrative anesthesia. Further dedicated studies and prospective trials are needed to confirm these findings.
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Affiliation(s)
- Alexandre Perez
- Unit of Oral Surgery and Implantology, Division of Oral and Maxillofacial Surgery, Department of Surgery, Faculty of Medicine, Hôpitaux Universitaires de Genève, 1211 Genève, Switzerland
| | - Steven Gernandt
- Division of Oral and Maxillofacial Surgery, Department of Surgery, Faculty of Medicine, Hôpitaux Universitaires de Genève, 1211 Genève, Switzerland
| | - Paolo Scolozzi
- Division of Oral and Maxillofacial Surgery, Department of Surgery, Faculty of Medicine, Hôpitaux Universitaires de Genève, 1211 Genève, Switzerland
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Li X, Liu Y, Li C, Wang J. Sedative and adverse effect comparison between oral midazolam and nitrous oxide inhalation in tooth extraction: a meta-analysis. BMC Oral Health 2023; 23:307. [PMID: 37210490 DOI: 10.1186/s12903-023-02965-5] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2023] [Accepted: 04/13/2023] [Indexed: 05/22/2023] Open
Abstract
OBJECTIVE Oral midazolam and nitrous oxide inhalation were commonly used sedative and analgesic techniques during tooth extraction. It is still controversial whether oral midazolam can replace the nitrous oxide inhalation for sedative and analgesic treatment of tooth extraction. Therefore, we conducted this study in order to provide a reference for doctors to choose effective sedative and analgesic treatment in tooth extraction. METHODS We searched the Chinese and English databases including PubMed, Embase, the Cochrane Library, China National Knowledge Infrastructure, Wanfang and VIP information databases. RESULTS Through this meta-analysis, we found that the success rate of sedation and analgesia treatment with oral midazolam during tooth extraction was 75.67% and the incidence of adverse reactions was 21.74%. The success rate of sedation and analgesia treatment using nitrous oxide inhalation during tooth extraction was 93.6% and the incidence of adverse reactions was 3.95%. CONCLUSION The use of nitrous oxide inhalation for sedation and analgesia during tooth extraction is very effective, and oral midazolam can be used as an alternative to nitrous oxide inhalation.
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Affiliation(s)
- Xia Li
- Ambulatory Surgical Center, West China Shool/Hospital of Stomatology Sichuan University, Sichuan Province, No. 14 The Renmin South Road, Chengdu, 610041, China
| | - Yali Liu
- Ambulatory Surgical Center, West China Shool/Hospital of Stomatology Sichuan University, Sichuan Province, No. 14 The Renmin South Road, Chengdu, 610041, China
| | - Chengjun Li
- Ambulatory Surgical Center, West China Shool/Hospital of Stomatology Sichuan University, Sichuan Province, No. 14 The Renmin South Road, Chengdu, 610041, China
| | - Jiexue Wang
- Ambulatory Surgical Center, West China Shool/Hospital of Stomatology Sichuan University, Sichuan Province, No. 14 The Renmin South Road, Chengdu, 610041, China.
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Dimic N, Djuric M, Nenadic I, Bojic S, Bobos M, Janicijevic A, Bojanic M, Mijovic M, Stevanovic P. Nitrous Oxide — Application in Modern Anesthesia. CURRENT ANESTHESIOLOGY REPORTS 2023. [DOI: 10.1007/s40140-023-00554-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/09/2023]
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Lohtrakul N, Wanapirak C, Tongsong T. Effectiveness of Nitrous Oxide versus Pethidine/Midazolam for Pain Relief in Minor Gynecological Operative Procedures: A Randomized Controlled Trial. MEDICINA (KAUNAS, LITHUANIA) 2023; 59:medicina59030611. [PMID: 36984612 PMCID: PMC10054065 DOI: 10.3390/medicina59030611] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/06/2023] [Revised: 03/08/2023] [Accepted: 03/16/2023] [Indexed: 03/30/2023]
Abstract
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.
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Affiliation(s)
- Napas Lohtrakul
- Department of Obstetrics and Gynecology, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand
| | - Chanane Wanapirak
- Department of Obstetrics and Gynecology, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand
| | - Theera Tongsong
- Department of Obstetrics and Gynecology, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand
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Rübsam ML, Kruse P, Dietzler Y, Kropf M, Bette B, Zarbock A, Kim SC, Hönemann C. A call for immediate climate action in anesthesiology: routine use of minimal or metabolic fresh gas flow reduces our ecological footprint. Can J Anaesth 2023; 70:301-312. [PMID: 36814057 PMCID: PMC10066075 DOI: 10.1007/s12630-022-02393-z] [Citation(s) in RCA: 15] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2022] [Revised: 10/28/2022] [Accepted: 10/31/2022] [Indexed: 02/24/2023] Open
Abstract
PURPOSE Climate change is a global threat, and inhalational anesthetics contribute to global warming by altering the photophysical properties of the atmosphere. On a global perspective, there is a fundamental need to reduce perioperative morbidity and mortality and to provide safe anesthesia. Thus, inhalational anesthetics will remain a significant source of emissions in the foreseeable future. It is, therefore, necessary to develop and implement strategies to minimize the consumption of inhalational anesthetics to reduce the ecological footprint of inhalational anesthesia. SOURCE We have integrated recent findings concerning climate change, characteristics of established inhalational anesthetics, complex simulative calculations, and clinical expertise to propose a practical and safe strategy to practice ecologically responsible anesthesia using inhalational anesthetics. PRINCIPAL FINDINGS Comparing the global warming potential of inhalational anesthetics, desflurane is about 20 times more potent than sevoflurane and five times more potent than isoflurane. Balanced anesthesia using low or minimal fresh gas flow (≤ 1 L·min-1) during the wash-in period and metabolic fresh gas flow (0.35 L·min-1) during steady-state maintenance reduces CO2 emissions and costs by approximately 50%. Total intravenous anesthesia and locoregional anesthesia represent further options for lowering greenhouse gas emissions. CONCLUSION Responsible anesthetic management choices should prioritize patient safety and consider all available options. If inhalational anesthesia is chosen, the use of minimal or metabolic fresh gas flow reduces the consumption of inhalational anesthetics significantly. Nitrous oxide should be avoided entirely as it contributes to depletion of the ozone layer, and desflurane should only be used in justified exceptional cases.
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Affiliation(s)
- Marie-Luise Rübsam
- Department of Anaesthesia, Intensive Care, Emergency and Pain Medicine, University Medicine of Greifswald, Greifswald, Germany
| | - Philippe Kruse
- Department of Anesthesiology and Intensive Care Medicine, University Hospital Bonn, Bonn, Germany
| | - Yvonne Dietzler
- Department of Anaesthesia, St. Marienhospital Vechta, Marienstraße 6-8, 49377, Vechta, Germany
| | - Miriam Kropf
- Department of Anaesthesia, Intensive Care, Emergency and Pain Medicine, BG Klinikum Hamburg, Hamburg, Germany
| | - Birgit Bette
- Department of Anesthesiology and Intensive Care Medicine, University Hospital Bonn, Bonn, Germany
| | - Alexander Zarbock
- Department of Anesthesiology and Critical Care, University Hospital of Muenster, Münster, Germany
| | - Se-Chan Kim
- Department of Anesthesiology and Intensive Care Medicine, University Hospital Bonn, Bonn, Germany
| | - Christian Hönemann
- Department of Anaesthesia, St. Marienhospital Vechta, Marienstraße 6-8, 49377, Vechta, Germany.
- Department of Anesthesiology and Critical Care, University Hospital of Muenster, Münster, Germany.
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Clouet R, Dajean-Trutaud S, Grall-Bronnec M, Bray E, Victorri-Vigneau C, Prud'homme T. Objectivation of the Equimolar Mixture of Oxygen and Nitrous Oxide Anxiolytic Effect in Pediatric Dentistry: A Pilot Study. Int J Clin Pediatr Dent 2023; 16:270-275. [PMID: 37519986 PMCID: PMC10373781 DOI: 10.5005/jp-journals-10005-2540] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/01/2023] Open
Abstract
Aim EMONO is an equimolar mixture of oxygen and nitrous oxide. Studies investigating its anxiolytic effect mostly used behavioral scales for assessing anxiolysis in children during dental care. Observing this effect objectively in a pediatric population could be very interesting. Materials and methods We conducted a prospective uncontrolled monocentric pilot study to assess the equimolar mixture of oxygen and nitrous oxide (EMONO) anxiolytic effect in children during dental care by monitoring heart rate (HR) variation. Results A statistically significant difference could be highlighted between the HR before the dental care and after 5 minutes of EMONO inhalation, illustrating the anxiolytic effect of EMONO in an objective way. HR variation also suggests that the effect of EMONO seems to prevent a return to the initial level of stress, even during anesthesia. Conclusion All of the data in the literature confirm the essential role of nitrous oxide in pediatric dental care. Demonstrating the effectiveness of EMONO by objective criteria is necessary. Trial registration Clinical Trials Unique Protocol ID: RC17_0275. How to cite this article Clouet R, Dajean-Trutaud S, Grall-Bronnec M, et al. Objectivation of the Equimolar Mixture of Oxygen and Nitrous Oxide Anxiolytic Effect in Pediatric Dentistry: A Pilot Study. Int J Clin Pediatr Dent 2023;16(2):270-275.
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Affiliation(s)
- Roselyne Clouet
- Department of Periodontology, Nantes Université, CHU Nantes, Service d’Odontologie, Nantes, France
| | - Sylvie Dajean-Trutaud
- Department of Periodontology, Nantes Université, CHU Nantes, Service d’Odontologie, Nantes, France
| | - Marie Grall-Bronnec
- Department of Periodontology, Nantes Université, CHU Nantes, INSERM, MethodS in Patients-centered outcomes and HEalth Research, SPHERE, Nantes, France
| | - Estelle Bray
- Department of Periodontology, Nantes Université, CHU Nantes, Service d’Odontologie, Nantes, France
| | - Caroline Victorri-Vigneau
- Department of Periodontology, Nantes Université, CHU Nantes, INSERM, MethodS in Patients-centered outcomes and HEalth Research, SPHERE, Nantes, France
| | - Tony Prud'homme
- Department of Periodontology, Nantes Université, CHU Nantes, Service d’Odontologie, Nantes, France
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Abstract
While there is not a wide range of pregnancy-specific drugs, there are some very specific high-risk areas of obstetric care for which unique pharmacological approaches have been established. In preterm birth, labor induction and augmentation, and the management of postpartum hemorrhage, these pharmacological approaches have become the bedrock in managing some of the most common and problematic areas of antenatal and intrapartum care. In this review, we summarize the existing established and emerging evidence that supports and broadens these pharmacological approaches to obstetric management and its impact on clinical practice. It is clear that existing therapeutics are limited. They have largely been developed from our knowledge of the physiology of the myometrium and act on hormonal receptors and their signaling pathways or on ion channels influencing excitability. Newer drugs in development are mostly refinements of these two approaches, but novel agents from plants and improved formulations are also discussed.
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Affiliation(s)
- Susan Wray
- Women's & Children's Health, Faculty of Health & Life Sciences, University of Liverpool, Liverpool, United Kingdom;
| | - Sarah Arrowsmith
- Department of Life Sciences, Manchester Metropolitan University, Manchester, United Kingdom
| | - Andrew Sharp
- Women's & Children's Health, Faculty of Health & Life Sciences, University of Liverpool, Liverpool, United Kingdom;
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Guerlais M, Aquizerate A, Lionnet A, Daveluy A, Duval M, Gérardin M, Istvan M, Laforgue EJ, Victorri-Vigneau C. Nitrous oxide: a unique official French addictovigilance national survey. Front Public Health 2023; 11:1167746. [PMID: 37206871 PMCID: PMC10189051 DOI: 10.3389/fpubh.2023.1167746] [Citation(s) in RCA: 14] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2023] [Accepted: 03/31/2023] [Indexed: 05/21/2023] Open
Abstract
Introduction Nitrous oxide has become over the last few years a public health problem in many countries. France has a dedicated health monitoring system dedicated to the surveillance of the abuse, dependence and consequences associated with the use of psychoactive substances coordinated by the French National Agency for the Safety of Medicines and Health Products.We present the French national survey of nitrous oxide. Materials and methods We analyzed all the cases with nitrous oxide from 2012 to 2021: number of notifications, characteristics of the subjects and consumption, consequences reported and their evolutions over time. In addition, we have made a special focus on the four main complications reported. Results A total of 525 cases were received with an exponential increase since 2019. We observed changes in the characteristics of the notifications with an increase in the proportion of women [42.7% in 2021 vs. 30.8% in 2020 (p = 0.02)]; an increase in the quantities consumed (use of cylinders); a negative evolution of the contexts of use with a search for self-therapeutic effects and use in violent contexts; an increasing trend of the severity of cases [78.1% in 2021 vs. 70.0% in 2020 (p = 0.07)].The main effects were substance use disorders and/or associated criteria (82.5%), neurological disorders (75.4%), psychiatric symptoms (15.4%) and cardiovascular events (8.6%). In terms of evolution, we observed a significant increase in cases with a use disorder and an increase in neurological complications. Moreover, new serious effects, notably cardiovascular events were reported. Discussion The combination of high availability, varied effects from euphoria to relief of discomfort in a stressful global pandemic context and the development of dependence could explain the rapid growth of consumption and the seriousness of the cases.It must now be taken into account that (i) Substance use disorders are associated with nitrous oxide consumption; (ii) clinicians must consider "nitrous oxide" in young subjects presenting different types of manifestations; and (iii) stopping consumption is imperative and is the first treatment. In this context, an addictological assessment must also be carried out.
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Affiliation(s)
- Marylène Guerlais
- Nantes Université, CHU Nantes, Service de Pharmacologie Clinique – Centre d’Evaluation et d’Information sur la Pharmacodépendance-Addictovigilance, Nantes, France
| | - Aurélie Aquizerate
- Nantes Université, CHU Nantes, Service de Pharmacologie Clinique – Centre d’Evaluation et d’Information sur la Pharmacodépendance-Addictovigilance, Nantes, France
| | - Arthur Lionnet
- Nantes Université, CHU Nantes, Service de Neurologie, Nantes, France
- Inserm, U1235, Nantes, France
| | - Amélie Daveluy
- Centre d’Addictovigilance, Département de Pharmacologie Médicale, INSERM, BPH, U1219, CHU de Bordeaux, Bordeaux, France
| | - Mélanie Duval
- Nantes Université, CHU Nantes, Service de Pharmacologie Clinique – Centre d’Evaluation et d’Information sur la Pharmacodépendance-Addictovigilance, Nantes, France
- Nantes Université, CHU Nantes, INSERM, methodS in Patient-centered outcomes and HEalth ResEarch, Nantes, France
| | - Marie Gérardin
- Nantes Université, CHU Nantes, Service de Pharmacologie Clinique – Centre d’Evaluation et d’Information sur la Pharmacodépendance-Addictovigilance, Nantes, France
| | - Marion Istvan
- Nantes Université, CHU Nantes, Service de Pharmacologie Clinique – Centre d’Evaluation et d’Information sur la Pharmacodépendance-Addictovigilance, Nantes, France
- Nantes Université, CHU Nantes, INSERM, methodS in Patient-centered outcomes and HEalth ResEarch, Nantes, France
| | - Edouard-Jules Laforgue
- Nantes Université, CHU Nantes, Service de Pharmacologie Clinique – Centre d’Evaluation et d’Information sur la Pharmacodépendance-Addictovigilance, Nantes, France
- Nantes Université, CHU Nantes, INSERM, methodS in Patient-centered outcomes and HEalth ResEarch, Nantes, France
| | - Caroline Victorri-Vigneau
- Nantes Université, CHU Nantes, Service de Pharmacologie Clinique – Centre d’Evaluation et d’Information sur la Pharmacodépendance-Addictovigilance, Nantes, France
- Nantes Université, CHU Nantes, INSERM, methodS in Patient-centered outcomes and HEalth ResEarch, Nantes, France
- *Correspondence: Caroline Victorri-Vigneau,
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Izumi Y, Hsu FF, Conway CR, Nagele P, Mennerick SJ, Zorumski CF. Nitrous Oxide, a Rapid Antidepressant, Has Ketamine-like Effects on Excitatory Transmission in the Adult Hippocampus. Biol Psychiatry 2022; 92:964-972. [PMID: 36050137 PMCID: PMC10107749 DOI: 10.1016/j.biopsych.2022.06.016] [Citation(s) in RCA: 20] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/16/2022] [Revised: 06/03/2022] [Accepted: 06/14/2022] [Indexed: 11/17/2022]
Abstract
BACKGROUND Nitrous oxide (N2O) is a noncompetitive inhibitor of NMDA receptors that appears to have ketamine-like rapid antidepressant effects in patients with treatment-resistant major depression. In preclinical studies, ketamine enhances glutamate-mediated synaptic transmission in the hippocampus and prefrontal cortex. In this study, we examined the effects of N2O on glutamate transmission in the hippocampus and compared its effects to those of ketamine. METHODS Glutamate-mediated synaptic transmission was studied in the CA1 region of hippocampal slices from adult albino rats using standard extracellular recording methods. Effects of N2O and ketamine at subanesthetic concentrations were evaluated by acute administration. RESULTS Akin to 1 μM ketamine, 30% N2O administered for 15-20 minutes resulted in persistent enhancement of synaptic responses mediated by both AMPA receptors and NMDA receptors. Synaptic enhancement by both N2O and ketamine was blocked by co-administration of a competitive NMDA receptor antagonist at saturating concentration, but only ketamine was blocked by an AMPA receptor antagonist. Synaptic enhancement by both agents involved TrkB (tropomyosin receptor kinase B), mTOR (mechanistic target of rapamycin), and NOS (nitric oxide synthase) with some differences between N2O and ketamine. N2O potentiation occluded enhancement by ketamine, and in vivo N2O exposure occluded further potentiation by both N2O and ketamine. CONCLUSIONS These results indicate that N2O has ketamine-like effects on hippocampal synaptic function at a subanesthetic, but therapeutically relevant concentration. These 2 rapid antidepressants have similar, but not identical mechanisms that result in persisting synaptic enhancement, possibly contributing to psychotropic actions.
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Affiliation(s)
- Yukitoshi Izumi
- Department of Psychiatry and Taylor Family Institute for Innovative Psychiatric Research, Washington University School of Medicine, St. Louis, Missouri; Center for Brain Research in Mood Disorders, Washington University School of Medicine, St. Louis, Missouri
| | - Fong-Fu Hsu
- Department of Medicine and Division of Endocrinology, Metabolism and Lipid Research, Washington University School of Medicine, St. Louis, Missouri
| | - Charles R Conway
- Department of Psychiatry and Taylor Family Institute for Innovative Psychiatric Research, Washington University School of Medicine, St. Louis, Missouri; Center for Brain Research in Mood Disorders, Washington University School of Medicine, St. Louis, Missouri
| | - Peter Nagele
- Department of Anesthesia and Critical Care, University of Chicago, Chicago, Illinois
| | - Steven J Mennerick
- Department of Psychiatry and Taylor Family Institute for Innovative Psychiatric Research, Washington University School of Medicine, St. Louis, Missouri; Center for Brain Research in Mood Disorders, Washington University School of Medicine, St. Louis, Missouri
| | - Charles F Zorumski
- Department of Psychiatry and Taylor Family Institute for Innovative Psychiatric Research, Washington University School of Medicine, St. Louis, Missouri; Center for Brain Research in Mood Disorders, Washington University School of Medicine, St. Louis, Missouri.
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Mechanisms Involved in the Neurotoxicity and Abuse Liability of Nitrous Oxide: A Narrative Review. Int J Mol Sci 2022; 23:ijms232314747. [PMID: 36499072 PMCID: PMC9738214 DOI: 10.3390/ijms232314747] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2022] [Revised: 11/21/2022] [Accepted: 11/22/2022] [Indexed: 11/29/2022] Open
Abstract
The recreational use of nitrous oxide (N2O) has increased over the years. At the same time, more N2O intoxications are presented to hospitals. The incidental use of N2O is relatively harmless, but heavy, frequent and chronic use comes with considerable health risks. Most importantly, N2O can inactivate the co-factor cobalamin, which, in turn, leads to paresthesia's, partial paralysis and generalized demyelinating polyneuropathy. In some patients, these disorders are irreversible. Several metabolic cascades have been identified by which N2O can cause harmful effects. Because these effects mostly occur after prolonged use, it raises the question of whether N2O has addictive properties, explaining its prolonged and frequent use at high dose. Several lines of evidence for N2O's dependence liability can be found in the literature, but the underlying mechanism of action remains controversial. N2O interacts with the opioid system, but N2O also acts as an N-methyl-D-aspartate (NMDA) receptor antagonist, by which it can cause dopamine disinhibition. In this narrative review, we provide a detailed description of animal and human evidence for N2O-induced abuse/dependence and for N2O-induced neurotoxicity.
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Moharrami M, Ali S, Dick BD, Moeinvaziri F, Amin M. The relationship between nitrous oxide sedation and psychosocial factors in the pediatric outpatient setting. Paediatr Anaesth 2022; 32:548-555. [PMID: 35020963 DOI: 10.1111/pan.14395] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/20/2021] [Revised: 12/23/2021] [Accepted: 01/07/2022] [Indexed: 11/30/2022]
Abstract
BACKGROUND Moderate sedation using nitrous oxide (N2 O) has become common in pediatric dentistry. However, less is known regarding the role of patients' characteristics and psychosocial factors in their cooperative behavior during dental procedures with N2 O. AIMS This study aimed to examine pediatric dental patients' behaviors while undergoing N2 O sedation and to measure the associations between child's cooperative behavior and demographic, physiological responses, and psychosocial factors. METHODS In this within-subject observational study, participants received 40% N2 O/O2 , by nasal hood, for non-surgical dental procedures. The main outcome measure was the extent of cooperative behaviors, as assessed by the Frankl scale at five timepoints, namely T1: pre-administration of N2 O, T2: post-administration of N2 O, T3: dental injection, T4: dental treatment, and T5: post-procedure administration of 100% O2 . Predictors included age, sex, psychosocial factors reported using the Parenting Style and Dimension Questionnaire and Spence Children Anxiety Scale, as well as pulse rate, respiratory rate, and oxygen saturation. The Wilcoxon signed-rank test and generalized estimation equation were used for data analyses. RESULTS In 80 children with a mean age of 7.2 (2.2) years, administration of N2 O was significantly associated with cooperative behaviors (odds ratio [OR]:2.62, confidence interval [CI]: 1.46-4.70, p = .001) when adjusted for other predictors. There was no interaction between any of the predictors and N2 O sedation on behaviors. Except for the authoritative parenting style (OR: 1.96, CI: 1.16-3.31, p = .012), which predicted more cooperative behaviors, other predictors were not associated with behavioral outcomes. CONCLUSION In children sedated with N2 O, behavior was independent of the child's demographic and psychosocial factors. While sedated, demographics, vital signs, and anxiety did not contribute to behavior management. However, screening for parenting style may help predict the child's behavioral response.
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Affiliation(s)
- Mohammad Moharrami
- Faculty of Medicine & Dentistry, School of Dentistry, University of Alberta, Edmonton, Alberta, Canada
| | - Samina Ali
- Department of Pediatrics, Faculty of Medicine & Dentistry, Women and Children's Health Research Institute, University of Alberta, Edmonton, Alberta, Canada
| | - Bruce D Dick
- Department of Anesthesiology and Pain Medicine, Faculty of Medicine & Dentistry, University of Alberta, Edmonton, Alberta, Canada
| | - Fardad Moeinvaziri
- Faculty of Medicine & Dentistry, School of Dentistry, University of Alberta, Edmonton, Alberta, Canada
| | - Maryam Amin
- Faculty of Medicine & Dentistry, School of Dentistry, University of Alberta, Edmonton, Alberta, Canada
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Omotosho YB, Ying GW, Orji R, Patel H. Recreational Nitrous Oxide-Induced Subacute Combined Degeneration. Cureus 2022; 14:e23409. [PMID: 35475085 PMCID: PMC9023326 DOI: 10.7759/cureus.23409] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/22/2022] [Indexed: 11/05/2022] Open
Abstract
Subacute combined degeneration (SCD) is myelopathy caused by vitamin B12 deficiency, leading to demyelination of the dorsal column located in the posterior spinal cord. Despite the high prevalence of recreational nitrous oxide use, its detrimental effects, including significant nerve dysfunction, are insufficiently recognized. We present the case of a 32-year-old male who was brought to the emergency department with complaints of paresthesia of his four extremities and lower extremity weakness. He was found to have B12 deficiency from chronic nitrous oxide abuse and responded positively to intramuscular B12 supplementation. It is important to consider possible nitrous oxide abuse while investigating suspected B12 deficiency, especially in patients presenting with nonspecific myeloneuropathy. Elevated methylmalonic acid (MMA) level is specific for diagnosing B12 deficiency. Prompt diagnosis and treatment can lead to the resolution of the symptoms and prevent further nerve damage.
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Seify H. Awake Plastic Surgery Procedures: The Use of a Sufentanil Sublingual Tablet to Improve Patient Experience. AESTHETIC SURGERY JOURNAL OPEN FORUM 2022; 4:ojab056. [PMID: 35350112 PMCID: PMC8942103 DOI: 10.1093/asjof/ojab056] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022] Open
Abstract
Background Awake plastic surgery performed under minimal sedation has advantages
including patient preference, affordability, and easier recovery compared to
when performed under deeper sedation. Commonly used oral analgesics may not
be adequate for awake procedures resulting in moderate to severe pain.
Sufentanil sublingual tablet (SST) 30 mcg has been shown to provide timely
analgesia with a safety profile appropriate for minimal-sedation
settings. Objectives To examine perioperative outcomes in patients who underwent awake plastic
surgery with local anesthesia and SST 30 mcg for pain control. Methods This study was a prospective single-group cohort study conducted at a single
plastic surgery center. SST 30 mcg was administered approximately 30 minutes
prior to the procedure. Outcome measures included the number of patients
with adverse events, the number of patients requiring medications in the
post-anesthesia care unit (PACU), and recovery time. Results Among the 31 patients, the most common procedures were liposuction (71%),
facelift (10%), and blepharoplasty (6%). The mean (± standard error
[SE]) procedural duration was 81 ± 9 minutes. No vital sign instability
or oxygen desaturation was observed. Three patients (10%) experienced
nausea, only one of which required treatment with oral ondansetron 4 mg in
the PACU. One patient (3%) experienced dizziness that did not require
treatment. No patients required opioids or other analgesics in the PACU for
pain. The mean (±SE) recovery time was 15 ± 4 minutes. Conclusions Awake plastic surgery can be performed using SST 30 mcg with minimal side
effects and a rapid recovery time. Level of Evidence: 4
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Pharmacologic Behavior Management (Sedation – General Anesthesia). Pediatr Dent 2022. [DOI: 10.1007/978-3-030-78003-6_8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
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Piazza GG, Iskandar G, Hennessy V, Zhao H, Walsh K, McDonnell J, Terhune DB, Das RK, Kamboj SK. Pharmacological modelling of dissociation and psychosis: an evaluation of the Clinician Administered Dissociative States Scale and Psychotomimetic States Inventory during nitrous oxide ('laughing gas')-induced anomalous states. Psychopharmacology (Berl) 2022; 239:2317-2329. [PMID: 35348804 PMCID: PMC9205822 DOI: 10.1007/s00213-022-06121-9] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/05/2021] [Accepted: 03/15/2022] [Indexed: 12/13/2022]
Abstract
RATIONALE A significant obstacle to an improved understanding of pathological dissociative and psychosis-like states is the lack of readily implemented pharmacological models of these experiences. Ketamine has dissociative and psychotomimetic effects but can be difficult to use outside of medical and clinical-research facilities. Alternatively, nitrous oxide (N2O) - like ketamine, a dissociative anaesthetic and NMDAR antagonist - has numerous properties that make it an attractive alternative for modelling dissociation and psychosis. However, development and testing of such pharmacological models relies on well-characterized measurement instruments. OBJECTIVES To examine the factor structures of the Clinician Administered Dissociative States Scale (CADSS) and Psychotomimetic States Inventory (PSI) administered during N2O inhalation in healthy volunteers. METHODS Secondary analyses of data pooled from three previous N2O studies with healthy volunteers. RESULTS Effect sizes for N2O-induced dissociation and psychotomimesis were comparable to effects reported in experimental studies with sub-anaesthetic ketamine in healthy volunteers. Although, like ketamine, a three-factor representation of N2O-induced dissociation was confirmed, and a more parsimonious two-factor model might be more appropriate. Bayesian exploratory factor analysis suggested that N2O-induced psychosis-like symptoms were adequately represented by two negative and two positive symptom factors. Hierarchical cluster analysis indicated minimal item overlap between the CADSS and PSI. CONCLUSION N2O and ketamine produce psychometrically similar dissociative states, although parallels in their psychosis-like effects remain to be determined. The CADSS and PSI tap largely non-overlapping experiences under N2O and we propose the use of both measures (or similar instruments) to comprehensively assess anomalous subjective states produced by dissociative NMDAR antagonists.
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Affiliation(s)
- Giulia G. Piazza
- grid.83440.3b0000000121901201Clinical Psychopharmacology Unit, Research Department of Clinical, Educational and Health Psychology, University College London, London, UK
| | - Georges Iskandar
- grid.83440.3b0000000121901201Clinical Psychopharmacology Unit, Research Department of Clinical, Educational and Health Psychology, University College London, London, UK ,grid.439749.40000 0004 0612 2754Department of Anaesthesia and Perioperative Medicine, University College London Hospital, London, UK
| | - Vanessa Hennessy
- grid.83440.3b0000000121901201Clinical Psychopharmacology Unit, Research Department of Clinical, Educational and Health Psychology, University College London, London, UK
| | - Hannah Zhao
- grid.83440.3b0000000121901201Clinical Psychopharmacology Unit, Research Department of Clinical, Educational and Health Psychology, University College London, London, UK
| | - Katie Walsh
- grid.83440.3b0000000121901201Clinical Psychopharmacology Unit, Research Department of Clinical, Educational and Health Psychology, University College London, London, UK
| | - Jeffrey McDonnell
- grid.83440.3b0000000121901201Clinical Psychopharmacology Unit, Research Department of Clinical, Educational and Health Psychology, University College London, London, UK
| | - Devin B. Terhune
- grid.4464.20000 0001 2161 2573Department of Psychology, Goldsmiths, University of London, London, UK
| | - Ravi K. Das
- grid.83440.3b0000000121901201Clinical Psychopharmacology Unit, Research Department of Clinical, Educational and Health Psychology, University College London, London, UK
| | - Sunjeev K. Kamboj
- grid.83440.3b0000000121901201Clinical Psychopharmacology Unit, Research Department of Clinical, Educational and Health Psychology, University College London, London, UK
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Combination of inhaled nitrous oxide and oral opioids induces long-lasting analgesic effects in patients with neuropathic pain: ProtoTOP study post hoc exploratory analyses. Pain 2021; 163:e1021-e1029. [PMID: 35050957 DOI: 10.1097/j.pain.0000000000002570] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2021] [Accepted: 12/14/2021] [Indexed: 11/26/2022]
Abstract
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 (N2O/O2) 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 N2O.
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Cao J, Ran L, Liu C, Li Z. Serum copper decrease and cerebellar atrophy in patients with nitrous oxide-induced subacute combined degeneration: two cases report. BMC Neurol 2021; 21:471. [PMID: 34863097 PMCID: PMC8643018 DOI: 10.1186/s12883-021-02496-y] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2021] [Accepted: 11/17/2021] [Indexed: 11/10/2022] Open
Abstract
Background Subacute combined degeneration (SCD) is a neurological complication commonly associated with vitamin B12 deficiency. It can result from nitrous oxide (N2O) abuse and cause neuropsychiatric symptoms. However, there has been no literature regarding alterations of serum copper and cerebellum in SCD patients. Case presentation We reported two cases of young SCD patients with histories of N2O abuse. In these cases, elevated homocysteine, macrocytic anemia, spinal cord abnormalities, and peripheral nerve injuries were detected. In addition, decreased serum copper level and cerebellar atrophy were reported for the first time. The patients’ symptoms improved after withdrawal of N2O exposure and vitamin B12 supplements. Conclusion We reported two SCD cases with serum copper alteration and cerebellar atrophy after N2O abuse for the first time. These might be crucial complements to the diagnosis of SCD.
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Affiliation(s)
- Jie Cao
- Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China
| | - Lusen Ran
- Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China
| | - Chenchen Liu
- Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China
| | - Zhijun Li
- Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
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Jiang PP, Guo YX, Yang XL, Xu J, Wang D. Effects of different remifentanil target concentrations on MAC BAR of sevoflurane in patients with liver dysfunction under carbon dioxide pneumoperitoneum stimulus: A randomized controlled trial. J Clin Pharm Ther 2021; 46:1776-1783. [PMID: 34514614 DOI: 10.1111/jcpt.13524] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2021] [Revised: 08/17/2021] [Accepted: 08/26/2021] [Indexed: 12/01/2022]
Abstract
WHAT IS KNOWN AND OBJECTIVE Remifentanil can effectively decrease the sevoflurane concentration to block sympathetic adrenergic response to CO2 pneumoperitoneum stimulus,and liver dysfunction will significantly reduce the MACBAR (minimum alveolar concentration for blocking adrenergic response) of sevoflurane. However, the effects of different remifentanil concentrations on the MACBAR of sevoflurane in patients with liver dysfunction are unclear. The aim of this study was to observe the effects of different remifentanil concentrations by intravenous target-controlled infusion on the MACBAR of sevoflurane in patients with grade B liver dysfunction under carbon dioxide pneumoperitoneum stimulus. METHODS Seventy-five patients with grade B liver dysfunction undergoing elective laparoscopic surgery were selected, and randomly divided into three groups with remifentanil plasma target concentrations of 0 (group R0 ), 1 (group R1 ) and 2 (group R2 ) ng/ml. Anaesthesia was induced by intravenous injection of propofol 2-3 mg/kg, remifentanil 2 μg/kg and cisatracurium 0.15 mg/kg. All groups were inhaled different concentrations of sevoflurane. The determination of sevoflurane MACBAR in each group was used a method of sequential-allocation technique, and venous blood samples were taken before and after the creation of carbon dioxide pneumoperitoneum to determine plasma adrenaline and noradrenaline concentrations. RESULTS AND DISCUSSIONS The MACBAR of sevoflurane in groups R0 , R1 and R2 was 4.83%, 3.00% and 2.10%, respectively. The MACBAR of sevoflurane was significantly difference among the three groups. When a similar effect of MACBAR had achieved in each group, no significant differences were found in the changes of plasma adrenaline and noradrenaline concentrations before and after the creation of pneumoperitoneum. What is new and conclusion Target-controlled infusion of different concentrations of remifentanil can reduce sevoflurane MACBAR during pneumoperitoneum stimulation in patients with liver dysfunction in some degree. However, the changes of plasma adrenaline and noradrenaline concentrations are consistent in the three groups when patient's stress response was inhibited at the same degree.
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Affiliation(s)
- Ping-Ping Jiang
- Department of Anesthesia, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan, China
| | - Yan-Xia Guo
- Department of Anesthesia, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan, China
| | - Xiao-Lin Yang
- Department of Anesthesia, The Second Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan, China
| | - Juan Xu
- Department of Anesthesia, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan, China
| | - Dan Wang
- Department of Anesthesia, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan, China
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Abstract
This article focuses on sedation/anesthesia of adolescent patients in the dental setting. Preoperative evaluation, treatment planning, monitoring, and management are critical components to successful sedation. The authors discuss commonly administered agents and techniques to adolescents, including nitrous oxide/oxygen analgesia. The levels and spectrum of sedation and anesthesia are reviewed. Common comorbidities are also presented as they relate to sedation of the adolescent dental patient.
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Affiliation(s)
- Matthew Cooke
- Department of Dental Anesthesiology, School of Dental Medicine, University of Pittsburgh, 3501 Terrace Street, Pittsburgh, PA 15261, USA; Department of Pediatric Dentistry, School of Dental Medicine, University of Pittsburgh, 3501 Terrace Street, Pittsburgh, PA 15261, USA.
| | - Thomas Tanbonliong
- Division of Pediatric Dentistry, Department of Orofacial Sciences, University of California San Francisco, School of Dentistry, Box 0753, 707 Parnassus Avenue, D-1021, San Francisco, CA 94143, USA
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50
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Multicenter Study Evaluating Nitrous Oxide Use for Labor Analgesia at High- and Low-Altitude Institutions. Anesth Analg 2021; 134:294-302. [PMID: 34469359 DOI: 10.1213/ane.0000000000005712] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
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.
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