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The effect of half percent oxymetazoline nasal drops on post-tonsillectomy cough, sore throat and bleeding in children; a double-blind randomized clinical trial
Mehrdad Masoudifar1, Ahmad Rezaeian2, Sheida Mosharaf3
1 Department of Anesthesiology, School of Medicine, Anesthesiology and Critical Care Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
2 Department of Otolaryngology, School of Medicine, Isfahan University of Medical Sciences Isfahan, Iran
3 Department of Anesthesiology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
| Date of Submission | 27-Jul-2022 |
| Date of Acceptance | 05-Oct-2022 |
| Date of Web Publication | 27-Jul-2023 |
Correspondence Address:
Dr. Sheida Mosharaf
Department of Anesthesiology, School of Medicine, Isfahan University of Medical Sciences, Isfahan
Iran
 Source of Support: None, Conflict of Interest: None  | Check |
DOI: 10.4103/abr.abr_247_22
Background: Considering the high prevalence of tonsillectomy in children and concerns of postoperative management, this study was conducted with the aim of evaluating the effects of oxymetazoline on bleeding, cough, and sore throat in children undergoing tonsillectomy.
Materials and Methods: The current double-blind clinical trial study was conducted on 88 tonsillectomy candidate patients. These patients were randomly divided into two groups. In the first group, oxymetazoline 0.05% nasal spray (OXY group) and in the second group, distilled water spray (Control group) was prescribed as one puff in each nostril immediately after anesthesia induction., the nasal spray was prescribed again in both nostrils at 12 h after tonsillectomy. Then the hemodynamic parameters, post-tonsillectomy hemorrhage (PTH) and sore throat were evaluated.
Results: The mean of the sore throat of children was not significantly different between the two groups in any of the follow-up times (P value >0.05). PTH in recovery and in the ward in the OXY group with the mean of 57.60 ± 71.82 ml and 22.11 ± 22.50 ml, respectively, was significantly lower than the control group (83.50 ± 113.64 ml and 27.52 ± 35.11 ml) (P value < 0.05). Also, the frequency of cough in the ward in the OXY group with 27.3% was significantly lower than the control group with 56.8% (P value = 0.005).
Conclusion: Regarding the results of the present study, sore throat and hemodynamic parameters did not change significantly with the administration of oxymetazoline. But this drug has played a significant role in reducing PTH and cough in children.
Keywords: Cough, hemorrhage, oxymetazoline, sore throat, tonsillectomy
How to cite this article:
Masoudifar M, Rezaeian A, Mosharaf S. The effect of half percent oxymetazoline nasal drops on post-tonsillectomy cough, sore throat and bleeding in children; a double-blind randomized clinical trial. Adv Biomed Res 2023;12:193 |
How to cite this URL:
Masoudifar M, Rezaeian A, Mosharaf S. The effect of half percent oxymetazoline nasal drops on post-tonsillectomy cough, sore throat and bleeding in children; a double-blind randomized clinical trial. Adv Biomed Res [serial online] 2023 [cited 2023 Sep 26];12:193. Available from: https://www.advbiores.net/text.asp?2023/12/1/193/382395 |
| Introduction | |  |
Tonsillectomy is one of the prevalent surgical procedures; more than 500,000 cases of tonsillectomy are performed on children annually in the United States.[1] Complications after this surgery may include pain, dehydration, and bleeding. Post- tonsillectomy hemorrhage (PTH) is one of the most serious complications. The incidence of primary PTH is estimated at 0.2% to 2.2% and secondary PTH is 0.1% to 0.3%. Therefore, it is a rare complication, but it can threaten the patient's life.[2],[3],[4]
Another important and common side effect after tonsillectomy in children is a sore throat, which mainly occurs after swallowing. This problem causes oral feeding to be incomplete and increases the possibility of vomiting, dehydration, and fever. Therefore, pain control is of particular importance due to reducing suffering and restlessness in these children and reducing the possibility of bleeding after surgery.[5],[6],[7]
Using new methods such as electrocautery has reduced the amount of bleeding after surgery. However, this method increases the pain and discomfort during swallowing and also increases the possibility of inflammation, edema, and spasm of the larynx muscles.[1],[4] The best time to start pain control is when the anesthetics have stopped and the patient is regaining consciousness. In general, pain control in the recovery room is the best time.[8] Post-tonsillectomy pain is routinely controlled with acetaminophen in combination with narcotics, such as codeine, pethidine, hydrocodone, or oxycodone although these drugs may have side effects. For example, in some cases, death has been reported due to respiratory depression in children who received codeine.[9] In addition, pethidine may be associated with serious complications of larynx spasms, laryngitis, and bleeding.[10] Therefore, the current concern about the rapid metabolism of narcotics in children undergoing tonsillectomy has made physicians re-evaluate pain treatment management post-tonsillectomy.
Scientific evidence is in favor of substituting non-steroidal anti-inflammatory drugs (NSAIDs), specifically ibuprofen, instead of narcotic drugs for post-surgery pain control. Although NSAIDs provide adequate analgesia after tonsillectomy, the use of NSAIDs also causes platelets dysfunction, which may lead to an increased risk of PTH.[11]
On the other hand, local nasal strengthening drugs (nasal drops) are used as two categories of sympathomimetic amines (such as phenylephrine hydrochloride) and imidazoline derivatives (such as oxymetazoline and xylometazoline) in the treatment of nasal mucus congestion in acute rhinitis caused by sinusoids dilatation and interstitial edema. In addition, they are used as an auxiliary treatment for nasal congestion associated with an acute or chronic runny nose, colds, sinusitis, hay fever, or other allergies.[12] These drugs are also used to treat epistaxis due to their vasoconstriction properties.[13]
Oxymetazoline is a sympathomimetic drug with a direct effect, which has significant alpha-adrenergic activity. It is a vasoconstrictor that reduces swelling and congestion when used for mucous membranes.[14] Also, oxymetazoline with a similar mechanism as cocaine can be used to control epistaxis. This drug is cheap, available, and can be used for a limited period of time as outpatient treatment.[13]
Some studies, however, have pointed to an increase in systemic absorption of this drug in high doses or due to vascular damage and stated that it can lead to systemic hemodynamic effects including systemic hypertension and pulmonary complications.[14],[15],[16],[17],[18],[19],[20]
These incidents can cause hemodynamic instability, deep bradycardia, pulmonary edema, and cardiac arrest. However, there is limited information available to describe oxymetazoline pharmacokinetics in children. Moreover, there is no information about the hemodynamic effect of oxymetazoline when used during general anesthesia. Hence, the present study set to evaluate the effects of oxymetazoline on cough, sore throat, and bleeding in children undergoing tonsillectomy.
| Materials and Methods | | |
This study was a double-blind randomized clinical trial. The population included all tonsillectomy candidate patients referred to Al-Zahra Hospital in Isfahan in 2021. Using the formula of sample size in the comparison of two groups, at the confidence level of 95%, the power test is 80%, and taking into account the results of previous studies that the mean sore throat in the two groups of case and control respectively with 16.1 ± 2.6 and 18.9 ± 2.7, the number of 88 patients was determined as a sample.
The inclusion criteria were the age of 6 to 12 years, candidates of tonsillectomy, and having ASA-1. Individuals having hypertension, sensitivity to oxymetazoline, and taking painkillers, antinausea, steroids, and antihistamines within 15 h before surgery were excluded from the study. Also, children who needed pre-surgery due to bleeding after surgery or had problems with intratracheal intubation were excluded from the study and replaced with other subjects.
After obtaining the code of ethics from the ethics committee of Isfahan University of Medical Sciences (approval code: IR.MUI.MED.REC.1400.377; https://ethics.research.ac.ir/EthicsProposalView.php?id = 208837) and clinical trial code (IRCT20110528006617N7; https://irct.ir/trial/58148) and written consent from eligible patients, about 88 patients participated in the study in a non-probabilistic manner. Then, they were divided into two groups using random allocation software. At the beginning of the study, the age and gender of the patients were recorded.
Then, all patients in both groups underwent surgery by a single skilled surgical team and the same type of surgery.
In the first group, 0.05% Oxymetazoline nasal spray (Raha Pharmaceutical Company) was prescribed as one puff in each nostril immediately after the induction of anesthesia.[13] In the second group, distilled water spray was prescribed immediately after induction of anesthesia as one puff in each nostril. Then, in both groups, 12 h after tonsillectomy, the nasal spray was prescribed again as one puff in each nostril.
To assent the blinding terms, both nasal sprays were prepared in advance by the pharmacist with the a similar shape, color, and smell as well as the same boxes and volume that were labeled A and B and available daily to the surgical team in the operating room. Then hemodynamic parameters including heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial pressure (MAP) were recorded at the beginning of recovery and at min 15, 30, 45, and 60 of recovery. The level of sore throat was evaluated and recorded based on the visual analog scale (VAS) upon entering the recovery room and at min 15, 30, 45, and 60 of recovery as well as upon entering the ward and min 15, 30, 45, and 60 being in the ward. The amount of bleeding during surgery and hospitalization in the ward was measured and recorded according to the weight of blood-soaked gases and the amount of suctioned blood, i.e., the weight of blood gauze was measured, and then the weight of an equal amount of dry gauze was subtracted from it to obtain the weight of blood-soaked gauze. To calculate blood volume, the obtained weight was divided by the density of blood, which is 1.055, and then the obtained number was considered as the volume of bleeding in the gauze.[20] For the suctioned blood, the volume of blood was obtained in the suction bottle, which is the combination of the patient's blood and washing serum; the amount of washing serum used was subtracted from it and the obtained value was considered the volume of the suctioned blood. Afterward, the sum of the volume of suctioned blood and the volume of blood impregnated with gauze was determined as the bleeding volume.
Nausea, vomiting, and cough of the patients were recorded up to 24 h after extubation. The dosage of analgesic, the first time of the analgesic request in the recovery room, and in the ward were also recorded.
Statistical analysis
Finally, the data were analyzed using SPSS 26. Data were shown as mean ± standard deviation (SD) or n (%). Assuming the results of the Kolmogorov–Smirnov test regarding the normal distribution of data, an independent t-test was used to compare the mean values of quantitative variables between two groups; the repeated measures ANOVA was applied to compare the mean values of quantitative variables with the passage of time in each of the two groups, and Chi-score test was used to compare the frequency distribution of qualitative variables. In all analyses, a significance level of <0.05 was considered.
| Results | | |
In the present study, there were 20 (45.5%) girls and 24 (54.5%) boys with the mean age of 10.41 ± 2.13 years in the OXY group, and 18 (40.9%) girls and 26 (59.1%) boys with a mean age of 9.70 ± 2.66 years in the control group. (P value > 0.05) [Table 1].
In addition, there was no significant difference between the two groups in the mean value of sore throat at the time of admission to recovery, up to the 60th min of recovery, at the time of admission to the ward, and up to 60 min after admission to the ward (P value > 0.05) and pain has decreased significantly with time in both groups (P value < 0.001) [Table 2]. In the evaluation of the hemodynamic parameters of the patients, it was also found that the HR of the patients did not differ significantly between the two groups at any of the follow-up times in the ward (P value > 0.05). In the OXY group SBP and MAP with the mean of 116.64 ± 7.82 and 88.86 ± 8.29 mmHg, respectively, were significantly higher than the control group with an average of 113.36 ± 5.60 and 85.66 ± 6.47 mmHg respectively at the 45th min of admission in the ward (P value < 0.05). On the other hand, during the 60 min in the ward, HR in both groups decreased significantly, but blood pressure (SBP, DBP, and MAP) in the OXY group had fewer changes than in the control group (P value > 0.05) [Table 3]. | Table 2: Comparison the mean of sore throat in the patients during the follow-up times between the two groups
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 | Table 3: Comparison of the patients' hemodynamic parameters during the follow-up times between the two groups
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In the evaluation of secondary outcomes, it was also found that the time of the first request for analgesics, its dose, and the time of starting the solid and liquid diet in recovery and in the ward were not significantly different between the two groups (P value > 0.05). In addition, the length of stay in recovery and extubation time did not differ between the two groups (P value > 0.05). But the amount of bleeding in the recovery and in the ward in the OXY group with the mean of 83.50 ± 113.64 mL and 27.52 ± 35.11 mL was significantly less than the control group with 57.60 ± 71.82 mL and 22.11 ± 22.50 mL, respectively (P value < 0.05). Also, the incidence of cough during recovery was not significantly different between the two groups, but the percentage of patients with cough in the ward was significantly lower than the control group (27.3% vs. 56.8%; P value = 0.005) [Table 4]. | Table 4: Comparison of secondary outcomes of patients between two groups
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| Discussion | | |
The results of the present study showed that PTH in the OXY group was significantly lower than in the control group in recovery room and in the ward. It suggests that the use of oxymetazoline plays a significant role in primary PTH control.
Oxymetazoline as an a-adrenergic agonist with more activity at the a2 versus a1 adrenergic receptor with the action at the peripheral a2- adrenergic receptor on the smooth muscle of the vasculature leads to vasoconstriction resulted in its clinical utility in the operating room during ear, nose, and throat (ENT) surgery as both a decongestant and a topical hemostatic agent, as well as off label to provide the nasal passages during nasal intubation and to better airway visualization and minimizing intraoperative or postoperative bleeding.[21],[22] It has been demonstrated the superior efficacy and safety profile in comparison with other topical agents of vasoconstrictive properties, such as cocaine, phenylephrine, or epinephrine.
The topical nasal mucosal applications of cocaine (4%), oxymetazoline (0.05%) and phenylephrine (0.25%) were compared in children during functional endoscopic sinus surgery by Riegle et al.[22] Phenylephrine was resulted to increase of blood pressure (BP), and oxymetazoline was associated with best subjective evaluation of bleeding and surgical visualization and suggested in children oxymetazoline as preferred vasoconstrictor. Higgins et al.[23] evaluated topical use of vasoconstrictors during ENT surgery and evaluated the efficacy against the risks of topical use of phenylephrine, oxymetazoline, and cocaine. They proposed to reduce the systemic complications of these agents in patients <12 years using 0.05% oxymetazoline as the initial vasoconstrictor.
Tonsillectomy with or without adenoidectomy is known as the most commonly used surgery in children's otolaryngology; but for many clinicians, post-tonsillectomy pain relief is still a problem to deal with, and supported by a large number of studies. Post-tonsillectomy pain can be due to inflammation, nerve irritation, and pharyngeal muscles spasms and the clinical importance of its control is related to the undesirable consequences of pain, including poor oral intake, sleep problems, dehydration, hospital re-admission, bleeding or changes in behavior. Chemokines, substance P, pro-inflammatory factors, and vasoactive intestinal peptides release during this surgery because of the local trauma of the oropharynx that induces vasodilatation, tissue edema, and pain.[24],[25]
In our study, during an hour in the ward, the mean of postoperative sore throat in both groups decreased significantly and there was no difference between the two groups in any of the follow-up times. It can be said that oxymetazoline did not have a significant role in reducing the sore throat of these children. Therefore, the two groups did not have significant differences in the time of the first request for analgesics and its dose.
It appears that topical use of nasal sprays containing steroids may help relieve pain after tonsillectomy, and it is suggested to repeat daily use of each tonsil fossa at home until the first follow-up. To our knowledge, no previous studies have examined the use of nasal steroids for post-tonsillectomy pain relief.
In a study by Unsal et al.,[26] children who used mometasone furoate nasal spray had less pain on the fifth postoperative day than children who were treated with paracetamol alone.
One of the concerns in the administration of oxymetazoline has been its effects on the hemodynamic parameters of the patients. In the evaluation of this issue in our study, it was found that the HR of children in recovery and the ward with the administration of oxymetazoline did not change significantly compared to the control group. But only the SBP and MAP in the 45th min of hospitalization in the OXY group were significantly higher than the control group. There was no significant difference between the two groups in terms of blood pressure during the 60 min after surgery.The effect of this drug on children's blood pressure was seen to be very small and transient.
Regarding the two case reports and some other studies, it was demonstrated the potential toxicity of over-the-counter (OTC) oxymetazoline, which may be prescribed without considering the volume administered, and this prescription is not limited to preoperative as toxicity has been reported with common indications including nasal decongestant. Despite the effects of topical application, vascular absorption can have profound systemic effects so usually hypertension is related to its effect on vascular smooth muscle α2-adrenergic receptors. In young children, it can also activate central adrenergic receptors when used in even larger doses and lead to serious potentially life-threatening adverse effects such as cardiovascular instability, sedation, and respiratory depression.[27],[28],[29],[30],[31],[32]
Imidazole derivatives, such as oxymetazoline, are rapidly absorbed through mucosal membranes in children, so toxicity can generally develop within minutes, but effects may take up to 24 h.[30],[31]
It should be noted that in the present study, no acute and serious complications threatened the children. The only common complication in these children was nausea and vomiting; without significant difference between the two groups. But the cough of children in the ward in the OXY group was significantly lower than the control group.The administration of this medicine was helpful to control the cough in these patients. In addition, due to the decrease in bleeding and cough in these patients, the time of starting the solid and liquid diet in the OXY group was less than in the control group, although this difference was not statistically significant in this study.
In a study by Shamil et al.[33] it has been concluded that intraoperative Otrivine (0.05% xylometazoline hydrochloride) for obstructive sleep apnoea may reduce post-operative respiratory compromise in pediatric undergoing adenotonsillectomy.
Panayi et al.[34] investigated the effect of a nasal decongestant on respiratory complications of post-adenotonsillectomy in pediatric patients with obstructive sleep apnea and suggested that Intraoperative Otrivine reduced intermediate and major interventions in thereafter recovery of pediatric patients with OSA. Higher adenoid/tonsil grading can be associated with intermediate and major interventions.
Oxymetazoline is only intended for short-term use of fewer than five days to treat recurrent nasal congestion and drug-induced rhinitis with long-term use, but there is still not enough information about systemic side effects and long-term use-induced end-organ injury and it seems necessary to develop guidelines for oxymetazoline dosing in children, especially infants and toddlers.[35],[36],[37]
It is noteworthy that our study is among the first studies that evaluate the effect of this drug on children; so it can provide an innovative perspective. However, the small sample size, and the lack of long-term follow-up of the patient's condition (at least 24 h after surgery) can be considered weak points of this study. The topical nasal decongestant oxymetazoline is an OTC medication and that is why its pediatric complications may be neglected. With attention to the nasal delivery via a spray mechanism or soaked cotton pledgets, it is necessary to consider the exact dose, and often there is no process in place to monitor the dose of oxymetazoline given. There are several reports of morbidity that makes it important to establish a consensus for responsible use. Now, considering these limitations and the possibility of side effects caused by this drug, there is a decision to prescribe or not to prescribe this drug in this age group, and there is a need for more studies to reach a definite result that can be generalized to society.
| Conclusion | | |
According to the results of the present study, the administration of oxymetazoline did not have a significant effect on the reduction of pain and the instability of hemodynamic parameters. But it has been able to significantly reduce PTH and cough in children. Therefore, it seems that this drug with the prescribed dose in this study can help with acceptable safety in managing the condition of children after tonsillectomy in terms of bleeding and cough.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity.
Financial support and sponsorship
Non
Nil.
Conflicts of interest
There are no conflicts of interest.
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[Table 1], [Table 2], [Table 3], [Table 4]
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