Patients with psychiatric, neurodegenerative or other conditions affecting olfaction were excluded. Autres ingrédients : eau purifiée, chlorure de sodium, citrate de sodium, chlorure de benzalkonium, acide citrique. Following monorhinal treatment with intranasal sodium citrate for 2 weeks, we demonstrated a significant reduction in the proportion of patients reporting phantosmia, but not parosmia. Sodium citrate, the sodium salt of citric acid, is safe to use and already licensed for medicinal uses in the stomach and bladder. Background: - 138.201.62.8. J Biol Chem 271(39):24231–24235, Wei J et al (1998) Phosphorylation and inhibition of olfactory adenylyl cyclase by CaM kinase II in neurons: A mechanism for attenuation of olfactory signals. The presence of parosmia and phantosmia was also assessed. NIH The effect of intranasal sodium citrate on olfaction in post-infectious loss: results from a prospective, placebo-controlled trial in 49 patients Further basic and clinical work is required to fully delineate the effect of intranasal sodium citrate in the treatment of post-infectious olfactory loss. Request PDF | Intranasal sodium citrate solution improves olfaction in post-viral hyposmia | Background: Calcium plays an integral role in olfactory signal transduction, including feedback inhibition. For each of the individual subcomponents of the SnSt, as well as the composite score, higher values indicate better olfactory function. Within the hyposmic subgroup, the reduction in proportion of patients reporting parosmia after treatment did not reach statistical significance (18 before and 10 after treatment, p = 0.055). Causes of hyposmia included: post-viral (7); posttraumatic (10); sinonasal disease (30) and idiopathic (10). To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. Epub 2020 Jun 25. Allergy Asthma Proc. A recent systematic review of the current literature concluded, however, that there was insufficient evidence or consensus to make recommendations on the management of this condition [29]. Sodium citrate reduces free intranasal calcium and is, therefore, thought to prevent calcium-mediated feedback inhibition at the level of the olfactory receptor. Furthermore, 23 of them (74.2%) realized an improvement in their own sense of smell. After treatment, 12 reported parosmia, 1 phantosmia. Methodology: Further research should investigative the effect of this treatment on qualitative olfactory dysfunction of varying cause. Rhinology 54:1–6, Hummel T et al (2017) Position paper on olfactory dysfunction. The buffer system of the present invention preferably contain a sodium or potassium phosphate/phosphoric acid buffer or a sodium or potassium acetate/acetic acid buffer or a sodium or potassium citrate/citric acid buffer in the range of 0.01 M to 0.5 M and preferably in the range of 0.05M to 0.2M. Medical Treatment of Traumatic Anosmia. We aimed to determine whether treatment with a 2-week course of intranasal sodium citrate improves quantitative olfactory function in patients with post-infectious impairment. All patients were treated with sodium citrate to the right nasal cavity (1 ml, 3.5 g/140 ml, pH 7.4, 298 mOsmol/L). Box and whisker plots showing change in TDI score (top left), threshold score (top right), discrimination score (bottom left) and identification score (bottom right) before and after treatment with intranasal sodium citrate (right) or no treatment (left). Statistical analysis was performed using GraphPad Prism (vGraphPad Software, LaJolla). No side effects were sufficiently severe to necessitate discontinuation of therapy. This study was approved by the Ethics Committee at the University Clinic of the TU Dresden, Dresden, Germany, and performed in accordance with the Declaration of Helsinki. We aimed to investigate the utility of intranasal sodium citrate in improving the olfactory function of hyposmic patients, by performing this prospective placebo controlled, single-blind trial. Thirty patients (96.8%) improved their scores in less than an hour period of time. To determine whether sodium citrate treatment led to significant improvement in quantitative olfactory function, we compared the change in olfactory test score [ΔTDI/T/D/I score = (TDI/T/D/I score after treatment)−(TDI/T/D/I score before treatment)] between right (treated) and left (untreated) sides. Within the anosmic subgroup, 5 reported parosmia and 5 phantosmia at baseline. When applied intranasally, a small number of previous clinical studies have demonstrated improved quantitative olfactory function. Patients were blinded to the side of sodium citrate application, and side of treatment was randomized between patients. With regard to phantosmia, various modalities have been trialled, including haloperidol, sodium valproate, phenytoin, topiramate, verapamil, nortriptyline, gabapentin, topical cocaine, transcranial magnetic stimulation and surgical excision of the olfactory mucosa. Error bars 5–95% interval. The results of this prospective controlled trial demonstrate that treatment with intranasal sodium citrate for a period of 2 weeks does not significantly improve quantitative olfactory function but does lead to a significant reduction in the proportion of patients reporting phantosmia. Rhinology 40(3):129–134, CAS  J Neurol 255(8):1121–1126, Article  We did, however, demonstrate a significant reduction in proportion of patients reporting phantosmia at the end of the study period. Monorhinal quantitative olfactory testing was undertaken before and after the full course of treatment, using the “Sniffin’ Sticks” (SnSt) test battery (Burghart Messtechnik, Germany). Le citrate de sodium est utilisé pour soulager l'inconfort de l'infection du tract urinaire comme la cystite, pour réduire l'acidose tubulaire rénale et peut aussi être utilisé comme laxatif osmotique. However, it is unclear why the observed effect occurred following monorhinal application, and without significant effect on quantitative olfactory function. In 2017, we performed a placebo-controlled trial in which sodium citrate was endoscopically applied to the right or left olfactory cleft, with physiological normal saline being applied as placebo control to the contralateral side. This site needs JavaScript to work properly. Chem Senses 22(1):39–52, Hummel T, Kobal G, Gudziol H, Mackay-Sim A (2007) Normative data for the ‘Sniffin’’ Sticks" including tests of odor identification, odor discrimination, and olfactory thresholds: An upgrade based on a group of more than 3,000 subjects’.  |  We aimed to determine whether treatment with a 2-week course of intranasal sodium citrate improves quantitative olfactory function in patients with post-infectious impairment. 2015 Mar;76(3):C41-2, C44-5. Author(s): Allen Loyd V Jr. Issue: Jan/Feb 2018 - Volume 22, Number 1 View All Articles in Issue. Following application, they were instructed to maintain this position for 1–2 min. Optical observation of insulin (e) at pH 4.4, 4.8, 5.2, and 5.6 and (f) at pH 4.4, 6.4, and 7.6 with PTD1 or PTD4. Chem Senses 23(4):453–457, Sato K, Suzuki N (2000) The contribution of a Ca2+-activated Cl- conductance to amino-acid-induced inward current responses of ciliated olfactory neurons of the rainbow trout. However, this improvement did not reach clinical significance (taken as ≥ 5.5 points). If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. Laryngoscope 127(2):291–295, Landis BN, Reden J, Haehner A (2010) Idiopathic phantosmia: outcome and clinical significance. Science 266(5189):1348–1354, Wayman GA, Impey S, Storm DR (1995) Ca2+ inhibition of type III adenylyl cyclase in vivo. A randomised controlled trial of sodium citrate spray for non-conductive olfactory disorders. We aimed to investigate the utility of intranasal sodium citrate in improving the olfactory function of hyposmic patients, by performing this prospective placebo controlled, single-blinded trial. Patients were instructed to apply the medication whilst lying in the ‘Kaiteki’ position, lying on the right side with neck turned laterally away from the bed by 20–30° and neck extended 20–40°. Several previous studies have supported this hypothesis, particularly in post‐infectious olfactory loss. Within the hyposmic subgroup, 18 reported parosmia and 12 reported phantosmia at baseline. Medicine and Health Sciences 1). 2018 Mar 11;10(1):32. doi: 10.3390/pharmaceutics10010032. In total, 60 participants with PIOD were recruited. 2017 Feb;274(2):803-808. doi: 10.1007/s00405-016-4277-x. The mean duration of olfactory dysfunction was 244 ± 238 days and mean time between testing was 23 ± 13 days. These pathways involve reduction in cation flow through CNG channels, either via direct interaction with calcium–calmodulin [8,9,10], or by calcium-dependent phosphorylation of adenylyl cyclase [11,12,13,14]. There was a trend towards greater increase in TDI (using best of two monorhinal scores) after treatment in younger patients compared with older patients, however, this did not reach statistical significance (mean increase in TDI score 4.89 ± 11.75 in patients under 61 and 3.24 ± 10.75 in patients aged 61 and over, p > 0.05). 2017 Sep 1;42(7):513-523. doi: 10.1093/chemse/bjx025. Box and whisker plot showing TDI scores before and after treatment with intranasal sodium citrate. It is possible that reducing intranasal free calcium over a prolonged period may result in equivalent results due to counterbalanced effects on depolarisation and inhibition. View. Authors: K.L. Subgroup analysis was also performed according to baseline quantitative olfactory function (hyposmia or anosmia) and age (< 61 or 61 +). Whitcroft, K.L., Gunder, N., Cuevas, M. et al. However, rising intracellular calcium concentration also initiates downstream pathways involved in receptor feedback inhibition. Please enable it to take advantage of the complete set of features! Eur Arch Otorhinolaryngol (2021). Chem Senses 39(3):185–194, Philpott CM, Boak D (2014) The impact of olfactory disorders in the United kingdom. Jordan says intranasal sodium citrate, a product of citric acid, has shown some promise; a study in Clinical Otolaryngology in 2017 found a sodium citrate … It has therefore been suggested that reduction of intranasal free calcium with buffer solutions such as sodium citrate may improve olfactory function in patients with smell impairment. We aimed to determine whether treatment with a 2-week course of intranasal sodium citrate improves quantitative olfactory function in patients with post-infectious impairment. --Description ; Informations nutritionnelles; Conseils d'util Patients applied intranasal sodium citrate solution to the right nasal cavity for 2 weeks. The effect of intranasal sodium citrate on olfaction in post-infectious loss: results from a prospective, placebo-controlled trial in 49 patients. (d) pharmacokinetic profile after intranasal administration of 100 μM insulin in 10 mM sodium citrate buffer at pH 4.4 with PTD1 or PTD4 to rats. The left nasal cavity was untreated and, therefore, acted as an internal control. Graduate School. USA.gov. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. 57 patients participated, aged 22-79. Rhinology 54(4):368–374, CAS  Fifty-seven patients with olfactory loss of mixed cause were recruited, and similar to Panagiotopoulos, we found a statistically significant improvement in odour threshold scores. Treatment with intranasal sodium citrate for a period of 2 weeks does not appear to improve quantitative olfactory function in patients with post-infectious impairment, compared to control. Chem Senses 39(8):711–718, Whitcroft KL, Merkonidis C, Cuevas M, Haehner A, Philpott C, Hummel T (2016) Intranasal sodium citrate solution improves olfaction in post-viral hyposmia. 2). In light of the significant reduction in reported phantosmia observed with sodium citrate therapy, we would speculate that this medication could be of use in treatment of such qualitative dysfunction. https://doi.org/10.1007/s00405-020-06567-7, DOI: https://doi.org/10.1007/s00405-020-06567-7, Over 10 million scientific documents at your fingertips, Not logged in Arch Otolaryngol Head Neck Surg 128(6):642–647. Previous studies have demonstrated improvement in short-term quantitative olfactory function following one-off application of sodium citrate. Clin Otolaryngol. Following one-off application with the ‘squirt device’, we found a statistically significant improvement in composite threshold + identification odour scores following treatment (mean improvement 0.87 ± 2.68 points, p = 0.04), but no significant improvement in individual threshold or identification scores alone. McGrae Hill Medical, New York, pp 712–735, Kramer RH, Siegelbaum SA (1992) Intracellular Ca2+ regulates the sensitivity of cyclic nucleotide-gated channels in olfactory receptor neurons. 2017 Jun;42(3):557-563. doi: 10.1111/coa.12789. In both of these studies, treatment-related improvements in olfactory test scores reached statistical, but not clinical significance. We therefore performed the following prospective controlled trial in 60 participants. However, there was also a reduction in the proportion of patients reporting phantosmia after treatment, which did reach statistical significance (17 before and 3 after treatment, p = 0.001) (Fig. Rhinology 43(2):130–134, PubMed  Int Forum Allergy Rhinol. Ten to fifteen drops were used in total. Second, whilst calcium is involved in downstream feedback inhibition of the olfactory receptor response, its role is not limited to inhibition, and is instead more neurobiologically complex. Results are given as mean ± standard deviation, unless stated otherwise. Treatment of post-viral olfactory dysfunction: an evidence-based review with recommendations. Results: The reduction in proportion of patients with phantosmia after treatment was statistically significant (8 before, 2 after, p = 0.039). Within the < 61 cohort, the reduction in proportion of patients reporting parosmia after treatment was not statistically significant (16 before and 11 after, p = 0.17). However, there was a significant reduction in the proportion of patients reporting phantosmia, at the end of the study period. Of these, 38 were female, 22 male and mean age was 61 years (range 25–85 years). Interdisciplinary Center for Smell & Taste, Department of Otorhinolaryngology, TU Dresden, Fetscherstrasse 74, 01307, Dresden, Germany, K. L. Whitcroft, N. Gunder, M. Cuevas, S. Menzel, A. Haehner & T. Hummel, Ear Institute, University College London, London, UK, Centre for the Study of the Senses, Institute of Philosophy, School of Advanced Studies, University of London, London, UK, You can also search for this author in Of interest, the successful treatment cases described in this review generally involved longer time periods than the present study (from 18 months to 11 years). Several reasons for the lack of treatment effect on quantitative function seen in this study may be postulated. Google Scholar, Betchen SA, Doty RL (1998) Bilateral detection thresholds in dextrals and sinistrals reflect the more sensitive side of the nose, which is not lateralized. NLM The application was with a glass pipette (‘dropper’). Sodium Citrate is the sodium salt of citrate with alkalinizing activity. Mean composite TDI score across all patients before treatment was 19.09 ± 6.31 (using best of two monorhinal scores, assuming that the better nostril determines overall olfactory function [23, 24]). The reduction in number of patients reporting phantosmia, however, was statistically significant (9 before, 1 after, p = 0.013). In turn, sodium and calcium ion influx into the cell causes depolarisation and action potential generation [7]. Sodium Citrate 9% Nasal Spray for Olfactory Disorders. No significant change in olfactory function occurred for either identification or threshold in any other aetiological subgroup. However, the reduction in the proportion of hyposmic patients reporting phantosmia was statistically significant (12 before and 1 after, p = 0.00078). Furthermore, the reduction in proportion of patients reporting phantosmia (5 before, 2 after) was not significant. Qualitative olfactory dysfunction, in the form of parosmia and phantosmia is relatively common in patients with PIOD [27]. CRC Press, Boca Raton, pp 203–224, Panagiotopoulos G, Naxakis S, Papavasiliou A, Filipakis K, Papatheodorou G, Goumas P (2005) Decreasing nasal mucus Ca++ improves hyposmia. Correspondence to doi: 10.12968/hmed.2015.76.3.C41. Politics, Philosophy, Language and Communication Studies. Google Scholar, Wei J, Wayman G, Storm DR (1996) Phosphorylation and inhibition of type III adenylyl cyclase by calmodulin-dependent protein kinase II in vivo. T. Hummel. Citrate- and Succinate-Modified Carbonate Apatite Nanoparticles with Loaded Doxorubicin Exhibit Potent Anticancer Activity against Breast Cancer Cells. Sodium citrate reduces free intranasal calcium and is, therefore, thought to prevent calcium-mediated feedback inhibition at the level of the olfactory receptor. In: Menini A (ed) The neurobiology of olfaction. Conclusions and Relevance This multifactorial assessment and patient olfactory training may improve the accuracy and reliability with which olfactory dysfunction is diagnosed and monitored. Of smell, sodium and calcium ion influx into the cell causes depolarisation and action potential generation 7... 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