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Effect of platelet-rich plasma on nasal mucociliary clearance after submucous diathermy of inferior turbinate

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ORIGINAL ARTICLE

Effect of platelet-rich plasma on nasal mucociliary

clearance after submucous diathermy of inferior turbinate

Ayman H. Salaheldin, Ahmed Hussein

*

The Department of Otorhinolaryngology, Faculty of Medicine, Cairo University, Egypt Received 16 February 2012; accepted 24 March 2012

Available online 8 June 2012

KEYWORDS Submucous diathermy; Platelet-rich plasma; Nasal mucociliary clearance

Abstract Objective: To determine the effectiveness of topical application of platelet -rich plasma (PRP) following submucous diathermy (SMD) in promoting the normal ciliary function and improving the healing of nasal turbinate.

Patients and methods: This is a prospective randomized single blinded study done on 60 patients with inferior turbinate hypertrophy (with no or minimal septal deviation). They were divided into 2 groups, study group A consisting of 30 patients who were candidates for bilateral SMD and then PRP was applied; and control group B (30 patients) who were candidates for the same surgery but saline was used instead of PRP. Both groups were followed up after 3 days postoperative, then at 1 week, 2 weeks, one month and 2 months consecutively. Nasal mucociliary clearance (NMC) before surgery was assessed (baseline) and was compared to the NMC in the week and two-month post operative periods.

Results: Nasal mucociliary clearance was improved in both patient groups but it was statistically more significant in group A (with PRP).

Conclusion: Platelet-rich plasma has an effective role after submucous diathermy in improve-ment of nasal mucociliary clearance and decreased incidence of bleeding and crust formation.

ª 2012 Egyptian Society of Ear, Nose, Throat and Allied Sciences. Production and hosting by Elsevier B.V. All rights reserved.

1. Introduction

Nasal obstruction is common in the adult population and may affect the patients’ health via prolonged respiratory infections,

secondary sinus involvement, diminution of the sense of smell, and sleep disorders.1–4 Etiology of chronic nasal obstruction due to hypertrophy of inferior turbinate is usually perennial allergic rhinitis and vasomotor rhinitis; the turbinate enlarge-ment of these patients is usually bilateral and is caused by thickening of the mucosa without hypertrophy of the underly-ing bony structure.5 Medical treatment including antihista-mine, topical and systemic steroids and allergen avoidance are used first but if these measures fail, surgery is advised including resection of the entire turbinate,6,7 cryosurgery,8,9 laser turbinectomy, sub mucosal diathermy (SMD)10 and

recently radiofrequency coblation technique.11

* Corresponding author.

E-mail address:[email protected](A. Hussein).

Peer review under responsibility of Egyptian Society of Ear, Nose, Throat and Allied Sciences.

Production and hosting by Elsevier

Egyptian Society of Ear, Nose, Throat and Allied Sciences

Egyptian Journal of Ear, Nose, Throat and Allied

Sciences

www.ejentas.com

2090-0740ª 2012 Egyptian Society of Ear, Nose, Throat and Allied Sciences. Production and hosting by Elsevier B.V. All rights reserved.

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The procedure of SMD was reported since 1907.12 The coagulative current in SMD is believed to do the tissue necrosis and fibrosis causing shrinkage of the soft tissue of the turbi-nate.13,14Although SMD is widely used and preferred by many surgeons, it is not free from complications which include adhe-sion, tissue sloughing, excessive scaring and bleeding.

The use of platelet-rich plasma in oral surgery was intro-duced in 1997 by Whitman et al.15and since that time different researches were done in oral surgery with different results about the effect of PRP on healing. Sanchez et al. 2003 con-cluded that there is no scientific evidence to support the use of PRP in combination with bone graft during augmentation procedures.16 On the other hand; Marx 2004 supported the use of PRP because it enhances soft tissue, mucosal and skin healing.17 PRP is tested in many different clinical situations to improve healing; here it is tested to see the effect on the heal-ing post SMD as measured by NMC and the possibility to minimize the post-operative complication of SMD.

2. Patients and methods

This study is a prospective single blinded randomized study done on 60 patients (36 males and 24 females), between March 2009 to March 2011. This study has been done after getting an approval from the local ethics committee and informed con-sents taken from the patients.

Age of the patients ranged from 18 to 50 with the mean 31.5. All the patients had inferior turbinate hypertrophy (with no or minimal septal deviation) causing chronic nasal obstruc-tion and did not respond to medical treatment. Patients were diagnosed and collected in the outpatient clinic based on his-tory, anterior rhinoscopy and rigid endoscopy. The following patients were excluded from the study: (1) patients with any bleeding disorder; (2) residence outside the city, incomplete ad-dress, or patients who were unable to come for follow up; (3) patients with associated marked septal deviation, nasal polyps, tumors or sinusitis; (4) patients with previous turbinate surgery and (5) patients with diabetes mellitus, uncontrolled hyperten-sion. Furthermore, patients with genetic disorder accompanied by ciliary dysfunction were also excluded.

Patients were divided into 2 groups, group A containing 30 patients and group B with the same number of patients. In the first group, SMD of the inferior turbinate was done followed by application of PRP (test group), whereas in the second group SMD was done without application of PRP and saline was ap-plied (control group). Surgery was done under general anesthe-sia and each patient was randomized (randomization done using the sealed envelope technique). The anesthesia was stan-dardized (same technique and same protocol) and no pre- med-ications were given. SMD was done using system 5000, 40 joules applied to a partially insulated gauge 18 cannula, the non insulated part was inserted submucosally into the inferior turbinate for about 1.5 cm from the anterior end on two succes-sive applications, one on the medial portion and the other on the inferior portion, the diathermy circuit is closed while the electrode is gradually withdrawn so that a submucosal linear burn results with minimal injury to the mucosal surface and avoid buttonholing of the mucosa. Postoperative nasal pack was not needed after surgery. A broad spectrum prophylactic postoperative antibiotic was prescribed to the patients, but

antihistamines, decongestants, analgesics, or nasal sprays were not given. All cases were discharged in the same day.

Follow up visits were scheduled after 3 days, 7 days, 2 weeks, 1 month, and 2 months post-operative. Data were collected from the preoperative period and in each postopera-tive visit then statistical analysis was done.

2.1. Technique of PRP preparation

Twenty-five milliliters of autologous blood drawn from the pa-tient during anesthesia induction were processed during SMD using a laboratory centrifuge (Heraeus labofuge 200, Ger-many). The blood was centrifuged on two sessions, the first one is called soft spin and allows the blood to be separated into 3 layers namely: bottom-most RBC layer, top-most acellular plasma layer which is called PPP (platelet-poor plasma) and the intermediate PRP layer which is called the Buffy coat. The PPP and PRP and some RBCs were transferred into an-other tube and underwent a second centrifugation called hard spin which is longer and faster than the first. This allows the platelet to settle at the bottom with few RBCs.18,19PRP was then mixed with an equal amount of calcified thrombin for activation and then applied directly to one side of the nose with syringe where it formed a matrix which looked like a blood clot.

2.2. Measurement of mucociliary function

Nasal mucociliary clearance was assessed by using the saccha-rin transit time (ST) test on the first day of the study as a base-line before SMD (patients with ST > 30 min were excluded) and was done after 2 weeks and 2 months postoperative. The patients were seated comfortably in the test room with con-stant humidity and room temperature of 20–22C for at least 20 min in order to keep them in a stable physiological and environmental state while instructions were given prior to test-ing. A 5 mg of saccharin particle was applied on the inferior turbinate 1.5 cm from the nares under direct visualization. After placement of saccharin, the patient was asked to refrain from sneezing, sniffing or bending. The transit time was re-corded from the placement of the saccharin on the inferior tur-binate until the patient reported a sweet taste to the nearest minute. Thirty minutes was set as the upper limit of the normal ST range.20

3. Results

Among the 60 patients included (36 males and 24 females), the age ranged between 18 and 52 years with a mean age of 31.5 years.

There were no postoperative infection, nor adhesions .Crust formation and mild bleeding were lesser in group A (2/30, 6.6%) than in group B (9/30, 30%). A transient worsening of nasal blockage was reported by 3 patients (10%) in group A and 6 patients (20%) in group B. A minimal postoperative pain was noted by 4 patients (13%) in group A and 6 patients (20%) in group B within the first 3 postoperative days. There was no statistical difference in mucociliary clearance between group 1 and group 2 before the operation as p value was 0.36 (Table 1).

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In group A, nasal mucociliary clearance mean was 15.97 ± 4.98SD before the operation, at 2 weeks and 2 months postoperatively, nasal mucociliary clearance mean was 12.77 ± 4.72 and 11.97 ± 4.53 respectively, the p value in this group was highly significant 0.004 (Table 2). In group B, pre-operative nasal mucociliary clearance mean was 17.13 ± 4.84 and in 2 weeks and 2 months after operation was 14.73 ± 4.28 and 13.87 ± 4.47 respectively and the p value was less significant (0.02) than in group A (Table 4). The post-operative improvement of NMC in group A and group B pa-tients at 2 months was greater than at 2 weeks as p value was more significant (Tables 3 and 5).

4. Discussion

Nasal obstruction is a common presenting symptom in otolar-yngology. Most patients have either septal deviation or hyper-trophic inferior turbinate. The treatment of hyperhyper-trophic inferior turbinate offers a wide range of surgical methods. However, early complications after surgical interference including bleeding, adhesion, and persistent nasal obstruction (due to edema and crust formation) remain as problems which lead to the search for minimal invasive surgeries.21Also, con-troversy remains in the appropriate surgical treatment of the inferior turbinate hypertrophy because the hypertrophy tends to recur after most treatments.22Surgical treatment for inferior turbinate hypertrophy was based on the assumption that an in-crease in nasal airway volumes will lead to a better functional nasal airflow and improvement of the symptoms. This is not

completely true, because an over aggressive approach, although this allows to completely solve the ventilation prob-lem, there is interference with the nasal physiology in a signif-icant way, so a wider nasal cavity does not necessarily mean that the nose functions are better.23It was noted that a huge postoperative increase in nasal airflow corresponds to a de-crease in the humidifying activity of the nasal mucosa with an excessive drying of nasal secretions and consequent crust formation. Moreover, the dramatic improvement in nasal air-flow following complete resection of the inferior turbinate is accompanied by a decrease in efficiency of the mucociliary transport and by a reduction in secretory IgA production.24 Successful surgical treatment of inferior turbinate hypertrophy requires reduction of tissue volume with preservation of muco-ciliary function. If little tissue is removed, the obstruction per-sists. If mucociliary function is impaired, patients report crusting.11

This study was conducted to determine if topical applica-tion of platelet-rich plasma (PRP) after submucous diathermy (SMD) will improve healing and normal ciliary function of na-sal turbinate. Platelet-rich plasma contains multiple growth and healing factors like platelet derived growth factor, trans-forming growth factor and vascular endothelial growth factor. The release of these factors is triggered by the activation of platelets which can be initiated by a variety of substance or stimuli such as thrombin, calcium chloride, collagen or adeno-sine 5c-diphosphate; in addition to these growth factors PRP contains fibrinogen and a number of adhesive glycoprotein that support cell migration.10

In this study, there was no statistical difference in mucocil-iary clearance between group A and group B before the oper-ation as p value was 0.36 (Table 1). It means that both groups were randomizely selected and there was no statistical bias which allows to compare mucociliary clearance postopera-tively in both groups. Crust formation and mild bleeding were lesser in group A (2/30, 6.6%) than in group B (9/30, 30%). This raised the importance of PRP in decreasing crust forma-tion and bleeding after SMD.

It was found in this study that mucociliary clearance in group A patients was improved postoperatively and this improvement increased at 2 months postoperative (p value

Table 1 Statistical difference in mucociliary clearance between group A and group B before the operation using independent sample T test.

Group N Mean Std. deviation Mean difference T Pvalue A 30 15.97 4.98 1.17 0.92 0.36 B 30 17.13 4.84

Table 2 Statistical difference in nasal mucociliary clearance before and after intervention in group A.

Time N Mean Std. deviation F Pvalue Before operation 30 15.97 4.98 5.97 0.004*

2 weeks 30 12.77 4.72 2 months 30 11.97 4.53

*

Means significant P < 0.05.

Table 3 Exact place of statistically significant difference of nasal mucociliary clearance before and after intervention using LSD (least statistical difference) test in group A.

Time (Compared group) Mean difference Pvalue 95% Confidence interval

Lower bound Upper bound

Before operation 2 weeks 3.20 .011* 0.76 5.64

2 months 4.00 .002* 1.56 6.44

2 weeks 2 months 0.8 0.52 1.64 3.24

* Means significant P < 0.05.

Table 4 Statistical difference in nasal mucociliary clearance before and after intervention in group B.

Time N Mean Std. Deviation F P value Before operation 30 17.13 4.84 4.17 0.02* 2 weeks 30 14.73 4.28

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was 0.011 at 2 weeks and 0.002 at 2 months) (Table 3). Similarly, the mucociliary clearance improvement in group B patients was more at 2 months (p value was 0.04 at 2 weeks and 0.01 at 2 months) (Table 5). The improvement of mucocil-iary clearance in group A (p value 0.004) was more compared to group B (p value 0.02). The improvement in NMC was more at 2 months postoperative because of less crustation and more healing of mucosa at that time. From the previous findings, it is concluded that SMD surgery leads to improvement in muco-ciliary clearance especially after 2 months and this improve-ment is increased if PRP is added during surgery.

Dale H. demonstrated that there are no benefits in the application of PRP after endoscopic sinus surgery and the study was terminated early after 13 operations.25In the study of Jakse et al. on the effects of PRP on bone regeneration after sinus lifting, they found a 3–4% increase in bone generation with PRP, the difference was not statistically significant – the regenerative capacity of PRP was described as being of ‘‘quite low potency’’.26 These previous research studies implied no significant effect in the application of PRP after surgery, this may be because the surface area needed for healing is large and cannot be covered all with PRP; this is because with current harvesting techniques, 20 ml of a patient’s blood yields only 2–3 ml of PRP.

In the present study, the topical application of PRP was sig-nificant in the improvement of NMC because the surface area needed for healing is not so large and also, there is less mucosal injury with SMD. Erkilet et al. suggested that platelet-rich plasma is effective in accelerating tympanic membrane perfo-ration healing in rats, and that it may be effective in human subjects, particularly as it is an autologous material.27The idea in Erkilet et al. study is similar to the present study in terms of the small surface area needed for healing. Also, Man et al. de-scribed the benefits of the use of PRP in cosmetic surgery.28

Also; Adler and Kent reported the advantage of using PRP in face-lifts.29 Finally, Abuzeni and Alexander reported the benefits of PRP in autologous fat transfer in cosmetic surgery.30

This study was done on 60 patients, only 30 of them with added PRP. Further studies are needed on larger numbers of patients with a longer period of follow up to evaluate the effect of adding PRP on nasal ciliary functions and healing of nasal mucosa after various nasal surgeries.

5. Conclusion

Submucous diathermy of inferior turbinate leads to improve-ment in nasal mucociliary clearance especially after 2 months.

If platelet rich plasma is added at the end of submucous dia-thermy surgery, there will be a greater improvement of nasal mucociliary clearance with less bleeding and crust formation. Platelet rich plasma is simple and easy to be prepared with no reported side effects.

References

[1] Englender M. Nasal laser mucotomy of the inferior turbinate. J Laryngol Otol. 1995;109:296–299.

[2] Fradis M, Golz A, Danino J, et al. Inferior turbinectomy versus submucous diathermy for the inferior turbinate hypertrophy. Ann Otol Rhinol Laryngol. 2000;109:1040–1045.

[3] Ophir D, Schnidel D, Halperin D, Marshak G. Long-term follow up of the effectiveness and safety of inferior turbinectomy. Plastic Reconstr Surg. 1992;90:980–7.

[4] Warwick-Brown NP, Marks NJ. Turbinate surgery: how effective is it? A long-term assessment. ORL J Otorhinolaryngol Relat Spec. 1987;49:314–320.

[5] Rakover Y, Rosen G. A comparison of partial inferior turbinec-tomy and cryosurgery for hypertrophic inferior turbinate. J Laryngol Otol. 1996;110:732–735.

[6] Moore G, Freeman TJ, Orgen FP, et al. Extended follow up of total inferior turbinate resection on relief of chronic nasal obstruction. Laryngoscope. 1985;95:1095–1099.

[7] Ophir D, Shapira A, Marshak G. Total inferior turbinectomy of nasal airway obstruction. Arch Otolaryngol. 1985;111:93–95. [8] Ozenberger YK. Cryosurgery for the treatment of the chronic

rhinitis. Laryngoscope. 1973;83:508–516.

[9] Bumsted RM. Cryosurgery for chronic vasomotor rhinitis: tech-nique and patient selection for improved results. Laryngoscope. 1984;94:539–544.

[10] Goode RL. Diagnosis and treatment of inferior turbinate dysfunction a self-instruction package. Washington DC Am Acad Otolaryngol. 1977;36–52.

[11] Coste A, Yona L, Blumen m. Radiofrequency is a safe and effective treatment of turbinate hypertrophy. Laryngoscope. 2001;111:894–899.

[12] Neres FE. Voltaic turbinate puncture for the relief of intumescent and hypertrophic rhinitis. J Am Med Assoc. 2001;49:1435–1438. [13] Wood CJ, Wickham MH, Smelt GJG, et al. Some observation on

submucous diathermy. J Laryngotol. 1985;103:1047–1049. [14] Wengraf CL, Gleeson MJ, Siodlak MZ. The stuffy nose a

comparative study of two methods of treatment. Clin Otolaryngol. 1986;11:61–68.

[15] Whitman DH, Berry RL, Green DM. Platelet gel: an autologous alternative to fibrin glue with applications in oral and maxillo-facial surgery. J Oral Maxillofac Surg. 1997;55:1294–1299. [16] Sanchez AR, Sheridan PJ, Kupp LI. Is platelet-rich plasma the

perfect enhancement factor? A current review. Int J Oral Maxillofac Implants. 2003;18:93–103.

[17] Marx RE. Platelet-rich plasma: evidence to support its use. J Oral Maxillofac Surg. 2004;62:489–496.

Table 5 Exact place of statistically significant difference of nasal mucociliary clearance before and after intervention using LSD (least statistical difference) test in group A.

Time (Compared group) Mean difference Pvalue 95% Confidence interval

Lower bound Upper bound

Before operation 2 weeks 2.4 0.04* 0.07 4.73

2 months 3.27 0.01* 0.94 5.60

2 weeks 2 months 0.87 0.46 1.46 3.20

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[18] Eby BW. Platelet-rich plasma harvesting with a single spin centrifuge. J Oral Implant. 2002;297:301–28.

[19] Sonnleitner D, Huemer P, Sullivan DY. A simplified technique for producing platelet-rich plasma and platelet concentrate for intraoral bone grafting: a technical note. Int J Oral Maxillofac Implant. 2000;15:879–882.

[20] Sakakura Y, Ukai K, Majima Y, Murai S, Harada T, Mioshi Y. Nasal mucociliary clearance under various conditions. Acta Otolaryngol (Stock h). 1983;96:167–173.

[21] Kizilkaya Z, Ceylian K, Emir H. Comparison of radiofrequency volume reduction and submucosal resection with microdebrider in inferior turbinate hypertrophy. Otolaryngol Head Neck Surg. 2008;138:176–181.

[22] Yaniz C, Mora N. Inferior turbinate debriding technique: ten-year result. Otolaryngol Head Neck Surg. 2008;138:170–175. [23] Sapci T, Sahin B, Karavus A, Akbulut UG. Comparison of the

effects of radiofrequency tissue ablation, CO2laser ablation, and

partial turbinectomy applications on nasal mucociliary functions. Laryngoscope. 2003;113:514–519.

[24] Salam MA, Wengraf C. Concho-antropexy or total inferior turbinectomy for hypertrophy of the inferior turbinates? A

prospective randomized study. J Laryngol Otol. 1993;107: 125–128.

[25] Dale H Rice. Platelet-rich plasma and endoscopic sinus surgery. Ear Nose Throat J. 2006;85(8):516–518.

[26] Jakse N, Tangl S, Gilli R, et al. The influence of PRP on the autogenous sinus grafts an experimental study on sheep. Clin Oral Implants Res. 2003;14:578–583.

[27] Erkilet E, Koyuncu M, Atmaca S, Yarim M. Platelet-rich plasma improves healing of tympanic membrane perforations: experimental study. J Laryngol Otol. 2009 May;123(5): 482–487.

[28] Man D, Plosker H, Winland-Brown JE. The use of autologous platelet-rich plasma (platelet gel) and autologous platelet-poor plasma (fibrin glue) in cosmetic surgery. Plast Reconstr Surg. 2001;107:229–237; discussion 238–239.

[29] Adler SC, Kent KJ. Enhancing wound healing with growth factors. Facial Plast Surg Clin North Am. 2002;10:129–146. [30] Abuzeni PZ, Alexander RW. Enhancement of autologous fat

transplantation with platelet-rich plasma. Am J Cosmet Surg. 2001;18:59–70.

References

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