Box and whisker plot showing TDI scores before and after treatment with intranasal sodium citrate. Boesveldt S, Postma EM, Boak D, Welge-Luessen A, Schöpf V, Mainland JD, Martens J, Ngai J, Duffy VB. Int Forum Allergy Rhinol. Epub 2020 Jun 25. Further basic and clinical work is required to fully delineate the effect of intranasal sodium citrate in the treatment of post‐infectious olfactory loss. Within the 61 + cohort, again the reduction in proportion of patients with parosmia was not statistically significant (7 before, 4 after treatment). 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, there was no reduction in proportion of patients with parosmia after treatment. Neuron 9(5):897–906, Chen TY, Yau KW (1994) Direct modulation by Ca(2+)-calmodulin of cyclic nucleotide-activated channel of rat olfactory receptor neurons. In our current study, overall mean TDI score (taken as best of two monorhinal scores) improved (ΔTDI = 2.08 ± 3.82, p < 0.0001) following 2 weeks of daily use. 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). Error bars 5–95% interval. 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). This concentration was shown to be effective in our previous studies. Furthermore, Ca2+ forms a significant proportion of the cation influx through CNG channels following olfactory receptor activation, and is therefore again involved in cell depolarisation [26]. Sodium citrate, the sodium salt of citric acid, is safe to use and already licensed for medicinal uses in the stomach and bladder. Work from our lab showed that one-off application of sodium citrate improved short-term psychophysical test scores in patients with post-infective olfactory dysfunction (PIOD) [6, 16]. Causes of hyposmia included: post-viral (7); posttraumatic (10); sinonasal disease (30) and idiopathic (10). NLM Given the small participant number in this group, we performed a further prospective, placebo-controlled trial in which sodium citrate again was applied monorhinally, with physiological sodium chloride applied to the contralateral cavity, in 49 patients with PIOD [22]. 2015 Mar;76(3):C41-2, C44-5. Previous work from Leopold and colleagues suggested that the pathogenesis of phantosmia may be related to peripheral dysfunction, at the level of the olfactory neuroepithelium [30]. Open Access funding enabled and organized by Projekt DEAL. In both of these studies, treatment-related improvements in olfactory test scores reached statistical, but not clinical significance. The proportion of patients reporting parosmia did not change significantly after treatment.  |  Neuron 15:169–179, Whitcroft KL, Cuevas M, Haehner A, Hummel T (2017) Patterns of olfactory impairment reflect underlying disease etiology. We therefore performed the following prospective controlled trial in 60 participants. PMID: 27316224 [PubMed - as supplied by publisher] Laryngoscope 127(2):291–295, Landis BN, Reden J, Haehner A (2010) Idiopathic phantosmia: outcome and clinical significance. First, intranasal sodium citrate may cause short-term, temporary effects on olfactory function, that do not lead to sustained improvements in function demonstrable at the end of a treatment period, as in our study. Accordingly, we found no significant difference between treated and untreated sides with respect to TDI, T, D and I (Fig. Results: Our reason for using the contralateral nostril as control was threefold: 1—use of an ‘internal’ control in this way reduces systematic differences between treated and non-treated groups and thereby reduces the risk of such differences confounding our results; 2—use of an internal control in this way increased the efficiency of our study design; 3—we demonstrated temporary improvement in quantitative olfactory function following a single, monorhinal application of sodium citrate in our previous work; therefore, elected to keep this study design [21, 22]. The application was with a glass pipette (‘dropper’). Sodium citrate is a calcium sequestrant. Intranasal sodium citrate solution improves olfaction in post-viral hyposmia. Sodium citrate acts as a calcium sequestrant and when applied intranasally, reduces free calcium available for feedback inhibition, which should theoretically improve olfaction. During this prospective trial of intranasal sodium citrate therapy, we found no significant effect of treatment on quantitative olfactory function, compared to control. 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). Sodium citrate acts as a calcium sequestrant and when applied intranasally, reduces free calcium available for feedback inhibition, which should theoretically improve olfaction. However, this study design incorporated frequent testing with the 12-item screening version of the SS identification test—which was performed every 15 min after instillation of the medication. Olfactory dysfunction affects approximately 20% of the adult population [1, 2], and can cause significant impact on quality of life [3, 4]. Whitcroft, K.L., Gunder, N., Cuevas, M. et al. Upon absorption, sodium citrate dissociates into sodium cations and citrate anions; organic citrate ions are metabolized to bicarbonate ions, resulting in an increase in the plasma bicarbonate concentration, the buffering of excess hydrogen ion, the raising of blood pH, and potentially the reversal of acidosis. Conclusions: Intranasal sodium citrate may be of benefit to patients with post-viral hyposmia. The effect of intranasal sodium citrate on olfaction in post-infectious loss: results from a prospective, placebo-controlled trial in 49 patients. To determine whether age related factors might have confounded potential treatment effect, we performed a further subgroup analysis according to age. --Description ; Informations nutritionnelles; Conseils d'util Olfactory dysfunction in acute rhinosinusitis: intranasal sodium hyaluronate as adjuvant treatment. Several reasons for the lack of treatment effect on quantitative function seen in this study may be postulated. Rhinology 43(2):130–134, PubMed  Due to this frequency of testing, it is possible that cue learning may have confounded the results obtained. This site needs JavaScript to work properly. For this reason, we speculated that prolonged use of intranasal sodium citrate might lead to clinically significant improvements in quantitative olfactory function. 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]). There was a reduction in the overall proportion of patients reporting parosmia after treatment that did not reach statistical significance (23 patients before and 15 after treatment; p = 0.17). Sodium citrate reduces free intranasal calcium and is, therefore, thought to prevent calcium-mediated feedback inhibition at the level of the olfactory receptor. In: Kandel E, Schwartz J, Jessell T, Siegelbaum A, Hudspeth A (eds) Principles of neural science, 5th edn. CONCLUSIONS: Intranasal sodium citrate may be of benefit to patients with post-viral hyposmia. At present, treatment options for qualitative olfactory dysfunction are limited, and their mechanisms poorly understood. This was based on histological analysis of neuroepithelium surgically excised from patients with phantosmia demonstrating changes such as reduced olfactory receptor neuron population; increased immature to mature neuron ratio; disordered axonal growth and presence of intraepithelial neuromas. 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. --L’Agence Fédérale du Médicament et des Produits de Santé (AFMPS, Belgique) considère que ce produit est un médicament et que son importation en Belgique devrait être soumise à une autorisation préalable. In the study, a group of people with anosmia or hyposmia were treated with a sodium citrate nasal spray, alongside a control group whose spray contained water. T. Hummel. 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. This efflux modulates the excitatory response of the olfactory receptor, and potentiates cell depolarisation [25]. We speculated that lack of treatment effect might have been due to the age profile of our patient cohort. Clin Otolaryngol 42(3):1–7, Frasnelli J, Livermore A, Soiffer A, Hummel T (2002) Comparison of lateralized and binasal olfactory thresholds. Classement du médicament en matière de délivrance : Médicament à usage vétérinaire. - 138.201.62.8. Rhinology 54(4):368–374, CAS  A randomised controlled trial of sodium citrate spray for non-conductive olfactory disorders. Again, this improvement reached statistical, but not clinical significance. Sodium citrate reduces free intranasal calcium and is, therefore, thought to prevent calcium-mediated feedback inhibition at the level of the olfactory receptor. Sodium Citrate is the sodium salt of citrate with alkalinizing activity. After treatment, 5 reported parosmia and 2 phantosmia. Sodium citrate acts as a calcium sequestrant and when applied intranasally, reduces free calcium available for feedback inhibition, which should theoretically improve olfaction. 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]. Conclusions and Relevance This multifactorial assessment and patient olfactory training may improve the accuracy and reliability with which olfactory dysfunction is diagnosed and monitored. Overall, there was a significant increase in TDI after treatment (using the best of right and left sides). The duration of effect of the citrate is transient, peaking at 30-60 minutes after application. Author(s): Allen Loyd V Jr. Issue: Jan/Feb 2018 - Volume 22, Number 1 View All Articles in Issue. Eur Arch Otorhinolaryngol (2021). This may explain the positive treatment effects seen in earlier studies, as compared with our present work. The aim of the present study was to determine whether prolonged use of intranasal sodium citrate improves quantitative and qualitative olfactory function in patients with PIOD. 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. Calcium plays an integral role in olfactory signal transduction, including feedback inhibition. Nature 368(6471):545–548, Liu MY, Chen TY, Ahamed B, Li J, Yau KW (1994) Calcium-calmodulin modulation of the olfactory cyclic nucleotide-gated cation channel. Within the anosmic subgroup, 5 reported parosmia and 5 phantosmia at baseline. Citrate- and Succinate-Modified Carbonate Apatite Nanoparticles with Loaded Doxorubicin Exhibit Potent Anticancer Activity against Breast Cancer Cells. 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. Patients with psychiatric, neurodegenerative or other conditions affecting olfaction were excluded. 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 However, rising intracellular calcium concentration also initiates downstream pathways involved in receptor feedback inhibition. Error bars 5–95% interval. 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. Of these, 38 were female, 22 male and mean age was 61 years (range 25–85 years). USA.gov. 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. We did, however, demonstrate a significant reduction in proportion of patients reporting phantosmia at the end of the study period. 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. 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. 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). 2017 Sep 1;42(7):513-523. doi: 10.1093/chemse/bjx025. No side effects were sufficiently severe to necessitate discontinuation of therapy. 2017 Feb;274(2):803-808. doi: 10.1007/s00405-016-4277-x. Conclusions: In total, 60 participants with PIOD were recruited. Treatment with medications such as phosphodiesterase inhibitors or intranasal sodium citrate require further research, as do nonchronic rhinosinusitis–related surgical procedures. K. L. Whitcroft and N. Gunder contributed equally. The reduction in number of patients reporting phantosmia, however, was statistically significant (9 before, 1 after, p = 0.013). When comparing change in monorhinal test scores, there was no significant effect of treatment in young or older cohorts. Get the latest public health information from CDC: https://www.coronavirus.gov, Get the latest research information from NIH: https://www.nih.gov/coronavirus, Find NCBI SARS-CoV-2 literature, sequence, and clinical content: https://www.ncbi.nlm.nih.gov/sars-cov-2/. Sodium citrate reduces free intranasal calcium and is, therefore, thought to prevent calcium-mediated feedback inhibition at the level of the olfactory receptor. Medicine and Health Sciences Further studies should be performed to systematically investigate the utility of this treatment in qualitative dysfunction of varying cause. Vennemann MM, Hummel T, Berger K (2008) The association between smoking and smell and taste impairment in the general population. Sodium citrate is known to ‘bind’ with calcium molecules, and stop them from acting in this way. However, there was a significant reduction in the proportion of patients reporting phantosmia, at the end of the study period. Inscription au tableau des substances vénéneuses (Liste I / II). Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Philpott CM, Erskine SE, Clark A, Leeper A, Salam M, Sharma R, Murty GE, Hummel T. Clin Otolaryngol. Article  Ciofalo A, de Vincentiis M, Zambetti G, Altissimi G, Fusconi M, Greco A, Ottaviano G, Magliulo G. Eur Arch Otorhinolaryngol. Would you like email updates of new search results? Compared with placebo, there was significant improvement in the identification scores of participants with post-viral hyposmia, following sodium citrate treatment. 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. 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. The reduction in proportion of patients with phantosmia after treatment was statistically significant (8 before, 2 after, p = 0.039). 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. Article. 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. (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. In: Menini A (ed) The neurobiology of olfaction. Google Scholar, Hummel T, Sekinger B, Wolf SR, Pauli E, Kobal G, Hummel T (1997) ‘Sniffin’ sticks’: olfactory performance assessed by the combined testing of odor identification, odor discrimination and olfactory threshold. NIH Sodium citrate acts as a calcium sequestrant and when applied intranasally, reduces free calcium available for feedback inhibition, which should theoretically improve olfaction. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. Laryngoscope 116(10):1858–1863, Whitcroft KL, Merkonidis C, Cuevas M, Haehner A, Philpott C, Hummel T (2016) Intranasal sodium citrate solution improves olfaction in post-viral hyposmia. Intranasal sodium citrate in quantitative and qualitative olfactory dysfunction: results from a prospective, controlled trial of prolonged use in 60 patients. Pharmaceutics. 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. Qualitative olfactory dysfunction (presence of parosmia or phantosmia) was also assessed before and after the treatment period through use of structured patient history. Sodium citrate is known to … Furthermore, the reduction in proportion of patients reporting phantosmia (5 before, 2 after) was not significant. Adult patients (> 18 years) with PIOD were recruited from the Smell and Taste Clinic at the Department for Otorhinolarnygology, TU Dresden. 3). Sodium Citrate 9% Nasal Spray for Olfactory Disorders. Patients continued treatment in this way two times per day for a period of 2 weeks. 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. J Neurol 255(8):1121–1126, Article  Qualitative olfactory dysfunction, in the form of parosmia and phantosmia is relatively common in patients with PIOD [27]. 2017; 42(3):557-563 (ISSN: 1749-4486) Whitcroft KL; Ezzat M; Cuevas M; Andrews P; Hummel T. OBJECTIVES: Free calcium plays an integral role in peripheral olfactory processing, including feedback inhibition. Authors: K.L. We have previously shown that treatment with intranasal sodium citrate may be beneficial in post-infectious olfactory dysfunction. Rhinol J 54(4):368–374, Whitcroft KL, Ezzat M, Cuevas M, Andrews P, Hummel T (2016) The effect of intranasal sodium citrate on olfaction in post-infectious loss: results from a prospective, placebo-controlled trial in 49 patients. European Archives of Oto-Rhino-Laryngology The left nasal cavity was untreated and, therefore, acted as an internal control. For detailed description of olfactory testing using the SnSt, please see ref [16]. Treatment with sodium citrate did not significantly improve quantitative olfactory function, compared to control. 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. Further research should investigative the effect of this treatment on qualitative olfactory dysfunction of varying cause. Glucose, Chlorure de sodium, Erythrosine, Glycine, Citrate de sodium, Citrate de potassium, Dihydrogénophosphate de potassium Forme pharmaceutique : Poudre. This medication can also prevent and treat certain metabolic problems (acidosis) caused by kidney disease.Citric acid and citrate salts (which contain potassium and sodium) belong to a class of drugs known as urinary alkalinizers. Abstract: A formulation for preparing Sodium Citrate 9% Nasal Spray for Olfactory Disorders. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. Citric acid and sodium citrate may also be used for other purposes not listed in this medication guide. Monorhinal olfactory testing for odour identification and threshold was performed in hyposmic patients using Sniffin Sticks, before and after treatment. Graduate School. National Center for Biotechnology Information, Unable to load your collection due to an error, Unable to load your delegates due to an error. Treatment of post-viral olfactory dysfunction: an evidence-based review with recommendations. Statistical analysis was performed using GraphPad Prism (vGraphPad Software, LaJolla). Rhinol Suppl. Extemporaneous compounding formulation for Citric Acid 6.7-mg/mL, Potassium Citrate 11-mg/mL and Sodium Citrate 10-mg/mL Aqueous Solution, Human, Veterinary (Polycitra), including components, quantities, instructions, and references Furthermore, we did not find a significant improvement in monorhinal olfactory function following treatment, compared to control. When applied intranasally, a small number of previous clinical studies have demonstrated improved quantitative olfactory function. Clin Otolaryngol 42(3):557–563, Buck LB, Bargmann CI (2013) Smell and taste: the chemical senses. We, therefore, divided our cohort according to age into two groups: patients below 61 years and patients aged 61 and older (61 being the median age in our cohort). Background: Show abstract. This validated psychophysical tool allows for the assessment of odour threshold, discrimination and cued identification, with composite scores being used to diagnose quantitative olfactory dysfunction [18, 19]. 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. PubMed  Autres ingrédients : eau purifiée, chlorure de sodium, citrate de sodium, chlorure de benzalkonium, acide citrique. COVID-19 is an emerging, rapidly evolving situation. After treatment, 12 reported parosmia, 1 phantosmia. Allergy Asthma Proc. Results are given as mean ± standard deviation, unless stated otherwise. Rhinology 54:1–6, Hummel T et al (2017) Position paper on olfactory dysfunction. 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