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Open Access 01-12-2024 | Nitrous Oxide | Study protocol

A nitrous oxide/oxygen fixed mixture to reduce pain induced by the hypodermic injection: study protocol for a randomized, controlled trial

Authors: Jun-Jun Zhang, Ping Yu, Hui Dang, Cheng-Shuang Feng, Xiu-Jiang Long, Wen-Fa Huang, Lei Wang, Jie-Ling Li, Guo-Liang Tian, Jia-Quan Wen, Jun-Hui Mei, Yu-Xiang Li

Published in: Trials | Issue 1/2024

Abstract

Background

Patients with hematological malignancies received multiple hypodermic injections of recombinant human granulocyte colony-stimulating factor. Procedural pain is one of the most common iatrogenic causes of pain in patients with hematological malignancies. It is also identified as the most commonly occurring problem in clinical care in the Department of Hematology and Oncology at Shenzhen University General Hospital. However, providing immediate relief from pain induced by hypodermic injection of recombinant human granulocyte colony-stimulating factor remains a major challenge. This trial aims to evaluate the safety and analgesic efficacy of a fixed nitrous oxide/oxygen mixture for patients with hematological malignancies and experiencing procedural pain caused by hypodermic injection of recombinant human granulocyte colony-stimulating factor in the department.

Methods

The nitrous oxide/oxygen study is a single-center, randomized, double-blind, placebo-controlled trial involving patients with hematological malignancies who require hypodermic injections of recombinant human granulocyte colony-stimulating factor for treatment. This trial was conducted in the Hematology and Oncology Department of Shenzhen University General Hospital. A total of 54 eligible patients were randomly allocated to either the fixed nitrous oxide/oxygen mixture group (n = 36) or the oxygen group (n = 18). Neither the investigators nor the patients known about the randomization list and the nature of the gas mixture in each cylinder. Outcomes were monitored at the baseline (T0), immediately after hypodermic injection of recombinant human granulocyte colony-stimulating factor (T1), and 5 min after hypodermic injection of recombinant human granulocyte colony-stimulating factor (T2) for each group. The primary outcome measure was the score in the numerical rating scale corresponding to the highest level of pain experienced during hypodermic injection of recombinant human granulocyte colony-stimulating factor. Secondary outcomes included the fear of pain, anxiety score, four physiological parameters, adverse effects, total time of gas administration, satisfaction from both patients and nurses, and the acceptance of the patients.

Discussion

This study focused on the safety and analgesic efficacy during hypodermic injection of recombinant human granulocyte colony-stimulating factor procedure. Data on the feasibility and safety of nitrous oxide/oxygen therapy was provided if proven beneficial to patients with hematological malignancies during hypodermic injection of recombinant human granulocyte colony-stimulating factor and widely administered to patients with procedural pain in the department.

Trial registration

Chinese Clinical Trial Register, ChiCTR2200061507. Registered on June 27, 2022. http://www.chictr.org.cn/edit.aspx?pid=170573&htm=4

Available only for authorised users

Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global Cancer Statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021;71(3):209–49. https://doi.org/10.3322/caac.21660.CrossRefPubMed

Siegel RL, Miller KD, Fuchs HE, Jemal A. Cancer statistics, 2022. CA Cancer J Clin. 2022;72:7–33. https://doi.org/10.3322/caac.21708.CrossRefPubMed

Li J, Smith A, Crouch S, Oliver S, Roman E. Estimating the prevalence of hematological malignancies and precursor condition suing data from Hematological Malignancy Research Network (HMRN). Cancer Causes Control. 2016;27(8):1019–26. https://doi.org/10.1007/s10552-016-0780-z.CrossRefPubMedPubMedCentral

Qiu H, Cao S, Xu R. Cancer incidence, mortality, and burden in China: a time-trend analysis and comparison with the United States and United Kingdom based on the global epidemiological data released in 2020. Cancer Commun (Lond). 2021;41(10):1037–48. https://doi.org/10.1002/cac2.12197.CrossRefPubMed

Hyuna S, Jacques F, Siegel Rebecca L, et al. Global Cancer Statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021;71(3):209–49. https://doi.org/10.3322/caac.21660.CrossRef

Zou DL, Guo MF, Zhou Q. A clinical study of pegylated recombinant human granulocyte colony stimulating factor (PEG-rhG-CSF) in preventing neutropenia during concurrent chemoradiotherapy of cervical cancer. BMC Cancer. 2021;21(1):661. https://doi.org/10.1186/s12885-021-08364-9.CrossRefPubMedPubMedCentral

Shang Jingling. Correlation of pegylated recombinant human granulocyte stimulating factor in secondary preventing neutropenia after chemotherapy in lung cancer. https://cdmd.cnki.com.cn/Article/CDMD-10161-1020097711.htm (2020). Accessed 16, Feb 2021. https://doi.org/10.26994/d.cnki.gdlyu.2020.000221

Yang WY, Liu TF, Chen XJ, Guo Y, Li T, et al. Pharmacokinetics and pharmacodynamics of pegylated recombinant human granulocyte colony-stimulating factor in children with acute lymphoblastic leukemia: a prospective control trial. Chin J Contemp Pediatr. 2020;22(11):1172–7. https://doi.org/10.7499/j.issn.1008-8830.2005048.CrossRef

Mao J. Histology and embryology. 9th ed. Beijing: People’s Sanitary Publishing Press; 2015.

10.

Zhao DY, Duan XX. Study on the correlation between the degree of operative pain, and pain fear and psychological resilience in patients with wounds. J Bengbu Med Coll 2021; 46(4): 557-561. https://doi.org/10.13898/j.cnki.issn.1000-2200.2021.04.033

11.

Gao LL, Yu JQ, Liu Q, Gao HX, Dai YL, et al. Analgesic effect of nitrous oxide/ oxygen mixture for traumatic pain in the emergency department: a randomized, double-blind study. J Emerg Med. 2019;57(4):444–52. https://doi.org/10.1016/j.jemermed.2019.06.026.CrossRefPubMed

12.

Gao HX, Zhang JJ, Liu N, Wang Y, Ma CX, Gao LL, et al. A fixed nitrous oxide/ oxygen mixture as an analgesic for patients with postherpetic neuralgia: study protocol for a randomized controlled trial. Trials. 2021;22(1):29. https://doi.org/10.1186/s13063-020-04960-5.CrossRefPubMedPubMedCentral

13.

Liu Q, Chai XM, Zhang JJ, Wang YL, Wang Y, et al. A fixed nitrous oxide and oxygen mixture for analgesia in children with leukemia with lumbar puncture-induced pain: a randomized, double-blind controlled trial. J Pain Symptom Manag. 2019;57:1043–50. https://doi.org/10.1016/j.jpainsymman.2019.02.029.CrossRef

14.

Liu Q, Gao LL, Dai YL, Li YX, Wang Y, et al. Nitrous oxide/oxygen mixture for analgesia in adult cancer patients with breakthrough pain: a randomized, double-blind controlled trial. Eur J Pain. 2018;22(3):492–500. https://doi.org/10.1002/ejp.1144.CrossRefPubMed

15.

Zhang JJ, Gao HX, Zhang TT, Bao WQ, Mou JY, et al. Pre-mixed nitrous oxide/ oxygen mixture treatment of pain induced by postoperative dressing change for perianal abscess: study protocol for a randomized, controlled trial. J Adv Nurs. 2020;76(12):3623–30. https://doi.org/10.1111/jan.14515.CrossRefPubMed

16.

Committee on Burn Injury and Tissue Repair of Association of Medical Exchanges Across the Taiwan Straits. Expert consensus on the application of mixed inhalation of nitrous oxide and sedation and analgesia technology in burn surgery. Chin J Burns. 2021;37(3):201–6, 2021 version, https://www.doc88.com/p-08647121589084.html. https://doi.org/10.3760/cma.j.cn501120-20200523-00284.CrossRef

17.

Kexing Biopharmaceutical Co. LTD. Human granulocyte colony-stimulating factor injection. http://www.kexing.com/product/3.html. Date Changed: 29 Sep 2019.

18.

Gao LL, Yang LS, Zhang JJ, Wang YL, Feng K, Ma L, et al. A fixed nitrous oxide/oxygen mixture as an analgesic for trauma patients in emergency department: study protocol for a randomized, controlled trial. Trials. 2018;19(1):527. https://doi.org/10.1186/s13063-018-2899-6.CrossRefPubMedPubMedCentral

19.

Wang YL, Gao HX, Wang JS, Wang JH, Bo L, et al. Immersive virtual reality as analgesia for women during hysterosalpingography: study protocol for a randomized controlled trial. Trials. 2020;21(1):102. https://doi.org/10.1186/s13063-019-4023-y.CrossRefPubMedPubMedCentral

20.

Center for Drug Evaluation. Guideline on Clinical Trial Data Monitoring Committees. https://max.book118.com/html/2019/0926/8030061072002052.shtm Accessed Sep 2019.

Title: A nitrous oxide/oxygen fixed mixture to reduce pain induced by the hypodermic injection: study protocol for a randomized, controlled trial
Authors: Jun-Jun Zhang
Ping Yu
Hui Dang
Cheng-Shuang Feng
Xiu-Jiang Long
Wen-Fa Huang
Lei Wang
Jie-Ling Li
Guo-Liang Tian
Jia-Quan Wen
Jun-Hui Mei
Yu-Xiang Li
Publication date: 01-12-2024
Publisher: BioMed Central
Keywords: Nitrous Oxide
Anxiety
Published in: Trials / Issue 1/2024
Electronic ISSN: 1745-6215
DOI: https://doi.org/10.1186/s13063-024-07919-y

At a glance: The STEP trials

Springer Medicine

A nitrous oxide/oxygen fixed mixture to reduce pain induced by the hypodermic injection: study protocol for a randomized, controlled trial

Abstract

Background

Methods

Discussion

Trial registration

At a glance: The STEP trials

Springer Medicine

Abstract

Background

Methods

Discussion

Trial registration

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