Original Research—Sleep Medicine and Surgery
Predictors of Surgical Outcomes of Uvulopalatopharyngoplasty for Obstructive Sleep Apnea Hypopnea Syndrome
Otolaryngology– Head and Neck Surgery 145(6) 1049–1054 Ó American Academy of Otolaryngology—Head and Neck Surgery Foundation 2011 Reprints and permission: sagepub.com/journalsPermissions.nav DOI: 10.1177/0194599811420811 http://otojournal.org
Yuan Ping Xiong, MD1,*, Hong Liang Yi, MD, PhD1,*, Shan Kai Yin, MD, PhD1, Li Li Meng, MD1, Xu Lan Tang, MD1, Jian Guan, MD1, Hui Ping Luo, MD1, Wei Tian Zhang, MD, PhD1, and Bin Chen, MD, PhD1
Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article.
Abstract Objectives. To investigate predictors of surgical outcomes of uvulopalatopharyngoplasty (UPPP) for obstructive sleep apnea hypopnea syndrome (OSAHS). Study Design. Case series with planned data collection. Setting. A university medical center. Subjects and Methods. Thirty-nine patients with OSAHS received Z-palatopharyngoplasty (ZPPP) or Han-uvulopalatopharyngoplasty (H-UPPP). All patients were evaluated within 3 months before surgery and at 6 to 12 months after surgery. Statistical analyses were conducted on preoperative parameters that could have affected surgical efficacy and outcome. Success was defined as an apnea–hypopnea index (AHI) fewer than 20 times per hour and a decrease of more than 50%. Results. The success rate was 56.4% (22/39 patients). There were statistically significant differences in AHI, lowest oxygen saturation (L-Sao2), time with oxygen saturation less than 90% (CT90), percentage of time with oxygen saturation less than 90% (CT90%), microarousal index (MI), apolipoprotein E (ApoE), high-density lipoprotein (HDL), fasting blood glucose (FBG), and Friedman OSA stage between the treatment success and failure groups. Higher success rate was predicted by lower severity, as indicated by lower AHI, CT90, CT90%, and MI; higher L-Sao2; and fewer glucose and lipid metabolism abnormalities, shown by lower ApoE and FBG and higher HDL. Conclusions. Disease severity, glucose and lipid metabolism, and Friedman OSA stage may be important predictors of surgical outcome of UPPP for OSAHS.
Keywords obstructive sleep apnea, uvulopalatopharyngoplasty, surgical outcome
Received April 13, 2011; revised July 27, 2011; accepted July 29, 2011.
I
t has been reported that the incidence of obstructive sleep apnea–hypopnea syndrome (OSAHS) in middle-aged people is 4% for men and 2% for women.1 The 5-year fatality rate in untreated cases is as high as 13%, and the fatality rate of patients with apnea–hypopnea index (AHI) greater than 20 is 37% in 8 years. OSAHS-related traffic accidents accounted for 25% of all traffic accidents, which was 2 to 7 times the level in the control group.2,3 Epidemiological studies have shown that OSAHS is an independent risk factor for hypertension, 30% of hypertensive patients suffer from OSAHS, and 50% to 80% of OSAHS patients have hypertension. In addition to increasing sympathetic activity and hypoxemia, repeated sleep apnea events can result in endothelial dysfunction, inflammation, platelet aggregation, and lipid metabolism disorders. Repeated short-term hypoxia stimulates central and peripheral chemoreceptors, leading to increased sympathetic activity, followed by increased release of glycogen; glycolysis is effectively reduced and insulin resistance increased with increased catecholamine secretion and a relative lack of pancreatic islet function caused by obesity, all of which result in increased blood sugar and further increases in glucose metabolism.4 As our understanding of OSAHS has developed, its influence in cardiovascular, cerebrovascular, respiratory, and cognitive diseases has become more apparent, which has led to a multidisciplinary research focus seeking to raise awareness of OSAHS and its treatment. Nasal continuous positive
1 Department of Otolaryngology, Affiliated Shanghai Sixth People’s Hospital of Shanghai Jiao Tong University, Shanghai, China * Contributed equally to this work as first authors.
Corresponding Author: Bin Chen, MD, PhD, Department of Otolaryngology, Affiliated Shanghai Sixth People’s Hospital of Shanghai Jiao Tong University, 600 Yishan Road, Shanghai City, China Email:
[email protected]
1050 airway pressure (nCPAP) is an effective treatment option for OSA. Despite technological progress, however, nCPAP remains a cumbersome treatment for which long-term compliance is 70% to 81%. Some nCPAP users even decide to give up treatment after a long time, with a withdrawal rate of about 24%.5,6 For some OSAHS patients, surgical treatment is also regarded as a good alternative. Uvulopalatopharyngoplasty (UPPP) is the most common surgical treatment; however, the long-term effects are not satisfactory, with a success rate of roughly 50%. Previous studies have suggested that the factors that usually affect surgical outcome include anatomical factors, disease severity, and airway dynamic problems; however, these factors cannot fully explain the poor surgical efficacy among OSAHS patients. Metabolic factors are considered to play an important role in the pathogenesis of OSAHS, which is considered to be a manifestation of metabolic syndrome.7-9 It has been suggested that metabolic factors also have an important impact on surgery.10 In the present study, to help establish the indications for UPPP, we followed patients after UPPP and analyzed preoperative parameters that could affect the efficacy and outcome of surgery in patients with OSAHS. Thirty-nine patients with OSAHS who had undergone pharyngeal surgery from May 2006 to September 2009 in our department were enrolled in this study.
Materials and Methods Clinical Data From May 2006 to September 2009, follow-up data were acquired from 39 patients with OSAHS (6 women, 33 men, age range 26-64 years, median 41 years). Patients primarily complained of nocturnal snoring and daytime drowsiness. By polysomnography (Alice 4; Respironics, Winter Park, Florida), they were diagnosed with OSAHS. Five cases were classed as moderate and 34 as severe according to the Friedman OSA stage system, which is co-determined by the Friedman tongue position (FTP), tonsil size, body mass index (BMI), and craniofacial and jaw shape.11 Eleven patients had grade I tonsils, 19 grade II, and 9 grade III. Three patients were FTP I, 18 were FTP II, 17 were FTP III, and 1 was FTP IV. Eight cases belonged to Friedman OSA stage I, 13 to stage II, and 18 to stage III. All candidates underwent a comprehensive clinical assessment including Epworth Sleepiness Scale score, snoring loudness, and quality of life assessment before the operation by experienced doctors.12,13 All patients were assessed for BMI and for neck, waist, and hip circumference. Cephalometric analysis was applied to ascertain the block levels in the palatopharynx according to posterior airway space (PAS) greater than 11 mm. Lipids, glucose, insulin, and liver and kidney function were tested. For those who had complications or medical diseases, relevant departments were consulted to control blood pressure or blood glucose and recover liver function; surgery was performed after complications and medical diseases were under control. All patients were informed of the importance of preoperative CPAP treatment.
Otolaryngology–Head and Neck Surgery 145(6) All the moderate and severe patients accepted 5 to 7 days of CPAP treatment to rectify systemic hypoxia in order to increase surgical tolerance. Informed written consent was obtained from all subjects prior to inclusion in the study. The study protocol was approved by the institutional review board of the Affiliated Sixth People’s Hospital of Shanghai Jiao Tong University.
Surgical Procedure All patients underwent Z-palatopharyngoplasty (ZPPP) or Han-uvulopalatopharyngoplasty (H-UPPP) under general anesthesia. The characteristics of H-UPPP were as follows.14 (1) Bilateral tonsillectomy was performed in all cases, and the redundant bilateral pharyngeal mucosa and submucosal tissue were trimmed or resected to enlarge the oropharyngeal lumen. (2) Two inverted V-shaped incisions were made on the ventral surface of the soft palate, along both sides of the uvula. Blunt dissection was used to remove surplus submembranous adipose tissue in the spatium veli palatini. Intact margins of the levator palatine, tensor palatine, and musculus uvularis and its corresponding mucosal membrane were preserved. (3) The dorsal and ventral margins of the preserved mucosal membrane of the uvula were closed with interrupted sutures, which formed a long new uvula. The palatoglossal arch and palatopharyngeal arch were also closed with interrupted sutures to enlarge and stabilize the oropharyngeal airway. The key surgical features of ZPPP were as follows.15 (1) Under general anesthesia, tonsillectomy was performed with a cold instrument or radiofrequency ablation Evac 70 (ArthroCare, Sunnyvale, California). (2) Two adjacent flaps were outlined on the palate, and the mucosa and fat tissue of the anterior aspect of the 2 flaps were removed. Then, the 2 flaps were separated from each other by splitting the palatal segment down the midline, and, finally, a 2-layer closure brought the midline all the way to the anterolateral margin of the palate. For 24 hours after surgery, the patients were monitored in the surgical intensive care unit. All patients received postoperative antibiotics and steroids.
Surgical Outcome Evaluation All patients were followed for 6 months, and according to the success criteria that were defined as AHI fewer than 20 times per hour and a decrease of 50% or more, the 39 patients were divided into responder and nonresponder groups.
Statistical Methods The SPSS software (version 13.0) was used to analyze preoperative parameters that could have affected surgical outcome. All the measurement material was represented as mean 6 standard deviation. A normal distribution of measurement data was tested by Student’s t test and the taxonomic data by the x2 test. P values \.05 were deemed to indicate statistical significance, and 95% confidence interval was determined.
Xiong et al
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Table 1. Baseline Physical Parameters for Responders and Nonresponders Responders Age, y Body mass index, kg/m2 Neck circumference, cm Waist circumference, cm Hip circumference, cm Waist–hip ratio
Nonresponders
41.55 6 10.60 27.84 6 2.58 40.50 6 3.96 96.18 6 8.49 100.82 6 7.387 0.954 60.048
Results According to the success criteria of AHI fewer than 20 times per hour and reduced by 50% or more, 22 cases were responders. The success rate was up to 56.4%. Among the 39 patients, 16 were in the H-UPPP group, with a success rate of 43.8%, whereas 23 were in the ZPPP group, with a success rate of 65.2%. There was no significant difference between the 2 surgical groups (P = .18). Age, gender, neck, waist, and hip circumference and waist–hip ratio showed no significant difference between responders and nonresponders (Table 1). Among the 39 patients with OSAHS, 5 had moderate and 34 had severe disease. The success rate for the moderate disease was 80.0% and for severe disease 52.9%; however, this difference was not statistically significant. The surgical success rate was 50.0%, 84.6%, and 38.9% for patients with Friedman OSA stage I, II, and III, respectively. Fisher exact test indicated that the differences among the 3 stage groups were significant. To further analyze whether tongue position or tonsil size affected the surgical outcome or Friedman OSA stage affected surgical efficacy, we analyzed statistically the success rate for each tongue position and tonsil size separately. The surgical success rates were 54.5%, 57.9%, and 55.6% for grades I, II, and III tonsil size, respectively; differences between the 3 groups were not statistically significant. The surgical success rate was 100%, 61.1%, 47.1%, and 0% in FTP I, II, III, and IV, respectively. Fisher exact test showed that there was no significant difference between the 2 groups (Table 2). In this study, routine preoperative blood examinations were conducted to check lipids, including total cholesterol (TC), triglyceride (TG), high-density lipoprotein (HDL), low-density lipoprotein (LDL), and apolipoprotein E (ApoE), fasting blood glucose (FBG), postprandial blood glucose, fasting insulin (FI), and postprandial blood insulin. There were significant differences in HDL, ApoE, FI, and FBG (Table 3) between responders and nonresponders. There were statistical significance in AHI, lowest oxygen saturation (L-Sao2), time with oxygen saturation less than 90% (CT90), percentage of time with oxygen saturation less than 90% (CT90%), and microarousal index (MI) (Table 4) between responders and nonresponders.
41.88 6 29.09 6 43.24 6 101.00 6 104.47 6 0.967 6
P Value
10.97 2.77 5.35 6.95 4.72 0.056
.923 .153 .074 .065 .084 .431
Table 2. Success Rate for Patients with Different Tonsil Size, Tongue Position, and Friedman OSA Stage
Tonsil size, grade
Friedman tongue position
Friedman OSA stage
1 2 3 I II III IV I II III
Success Rate, %
x2
P
54.5 57.9 55.6 100 61.1 47.1 0 50 84.6 38.9
0.35
.983
4.379
.224
6.587
.037
Discussion OSAHS is a common sleep disorder characterized by repeated upper airway obstruction during sleep and excessive daytime sleepiness. UPPP was introduced by Fujita in 1981 to expand the pharyngeal cavity to treat OSAHS, and it has been developed and improved in the last 30 years. Through various means to evaluate the obstructive sites, specific surgeries have been used successfully; however, many patients still fail to obtain a cure. This may be related to different epidemiological factors. It has been shown that the incidence of OSAHS is related to many complex factors, including upper airway anatomy, neuromuscular regulation, and metabolic factors.16 The present study focused on the relationship between anatomical factors and surgical efficacy. Friedman et al11,17 reported a clinical analysis of OSAHS patients, based on partial upper airway anatomical structure, such as tonsil size, tongue position, and BMI, and found that UPPP success rates in patients with Friedman OSA stage I, II, and III were 80%, 37.9%, and 8.1%, respectively. When the patients with stage II and III received additional tongue base radiofrequency ablation, their success rate increased to 74% and 43.8%, respectively.11,17 Millman et al18 and others have found that the vertical distance from the mandibular plane to the hyoid (MPH), which is the accepted parameter for hyoid descensus, could predict the results of
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Otolaryngology–Head and Neck Surgery 145(6)
Table 3. Baseline Lipid and Glucose of Responders and Nonresponders
TC TG HDL LDL ApoE FI PI FBG F2hBG
Responders, mmol/L
Nonresponders, mmol/L
P Value
Mean Difference (95% CI)
4.93 6 0.6 2.5 6 2.35 1.17 6 0.027 3.06 6 0.52 5.34 6 1.25 7.51 6 1.94 88.6 6 22.9 5.49 6 0.74 6.81 6 1.81
4.94 6 1.04 3.91 6 0.13 0.96 6 0.13 2.97 6 0.74 6.76 6 2.02 29.6 6 19.4 96.7 6 75.3 6.33 6 1.55 7.88 6 2.89
.978 .99 .014 .682 .024 .023 .749 .031 .200
0.01 (20.59 to 0.61) 1.41 (20.28 to 3.10) 20.21 (20.36 to –0.06) 20.09 (20.57 to 0.38) 1.42 (0.15 to 2.68) 22.09 (2.81 to 24.9) 8.1 (254.43 to 74.47) 0.84 (0.08 to 1.60) 1.07 (20.59 to 2.73)
Abbreviations: ApoE, apolipoprotein E; CI, confidence interval; FBG, fasting blood glucose; FI, fasting insulin; F2hBG, postprandial blood glucose; HDL, highdensity lipoprotein; LDL, low-density lipoprotein; PI, postprandial blood insulin; TC, total cholesterol; TG, triglyceride.
Table 4. Baseline Polysomnography Parameters of Responders and Nonresponders AHI, events/h
L-Sao2,%
CT90, min
CT90%
MI, events/h
Responders 57.3 6 19.3 72.82 6 10.901 73.45 6 61.022 21.9 6 17.2 46.8 6 20.0 Nonresponders 71.1 6 18.9 65.59 6 9.741 163.38 6 85.552 46.0 6 21.0 64.2 6 18.1 P value .042 .036 .001 .001 .008 Mean Difference (95% CI) 13.8 (1.25 to 26.3) 27.23 (214.04 to 20.42) 89.93 (38.43 to 141.4) 24.1 (11.28 to 36.83) 17.4 (4.62 to 30.23) Abbreviations: AHI, apnea–hypopnea index; CI, confidence interval; CT90, time with oxygen saturation less than 90%; CT90%, percentage of time with oxygen saturation less than 90%; L-Sao2, lowest oxygen saturation; MI, microarousal index.
UPPP: if MPH was greater than 20 mm, signifying hyoid descensus, the effective rate of UPPP was 20.6%; if MPH was 20 mm or less, signifying a normal hyoid position, the effective rate of UPPP was 75%.18 A recent study by Yi et al15 found that patients with Friedman OSA stage II and PAS greater than 11 mm had a success rate of 87.5% by ZPPP, whereas the success rate was 44.4% in patients with stage III disease with the same PAS. All 3 of these studies demonstrated that partial upper airway anatomical abnormalities, to a certain extent, affect surgical efficacy. In the present study, significant differences were not found in the surgical success rate in patients with different FTP classifications. In contrast, the differences in surgical success rate among the patients with different Friedman OSA stages were significant, suggesting that tongue position and tonsil size do not affect surgical outcome independently; however, the co-determined Friedman OSA stage did affect surgical efficacy. Abnormal metabolic factors are important epidemiological factors for OSAHS. Several studies have suggested that high blood pressure, diabetes, and obesity are closely associated with OSAHS,4,19-23 and some researchers believe that OSAHS may simply be a manifestation of metabolic syndrome.10 Vgontzas et al24 showed that obesity, especially central obesity, was related to OSAHS. A follow-up study suggested that patients with obesity and OSAHS are very likely to have metabolic syndrome, owing to their common clinical manifestations. There is a high prevalence of MS
among patients with OSA, and even among nonobese patients, OSA is associated with risk factors for MS.9,10 In the present study, we found that there were significant differences between responders and nonresponders for HDL, ApoE, FBG, and FI. Through binding to low-density lipoprotein cholesterol (LDL-C), very low density lipoprotein cholesterol (VLDL-C), and LDL-C-related protein, ApoE plays an important role in the transport and metabolism of plasma TC and TG. There are 3 major alleles, E2, E3, and E4, in the gene that encodes ApoE. ApoEE4 is closely related to high TC and LDL-C, which is considered to be an important genetic marker of lipid metabolism, coronary heart disease, and Alzheimer’s disease (AD).25 Some studies have suggested that ApoEE4 could also be one of the large number of genetic factors related to OSAHS susceptibility,26-28 which is independent of gender and BMI; its overall relative risk is 1.41 to 2.0. Another small-sample study suggested that there is a relationship between ApoEE4 and OSAHS. Additionally, based on a study of ApoEE4 and AD, it has been proposed that ApoEE4 is associated with brain stem respiratory center degeneration and motor neuron excitability reduction, which causes upper airway dilator muscle dysfunction, which may be a mechanism by which ApoEE4 is involved in the pathogenesis of OSAHS.29 Summarizing the previous studies, ApoE plays an important role in the pathogenesis of OSAHS. The results of the present study suggest that for OSAHS patients with abnormal ApoE, surgery should be undertaken carefully because
Xiong et al abnormal ApoE could indicate upper airway dilator muscle dysfunction, which could adversely affect surgical outcome. In the present study, according to the diagnostic criteria of MS,30 patients were divided into 2 groups: MS (n = 16) and non-MS (n = 23), with respective surgical success rates of 43.5% and 75.0%, although this difference was not statistically significant (P = .051); it probably was attributable to the small sample size. Thus, larger numbers of patients are required to confirm these results in future studies. Certain disputes exist over the effects of disease severity on surgical outcome. Through follow-up of 22 patients with OSAHS with the same Friedman stage, Richard et al31 found that the surgical success rates in patients with AHI greater than 55 and less than 55 were 0% and 56%, respectively, and no significant difference was found between the success rates for different surgical methods.31 One hundred and thirty-four OSAHS patients were followed after UPPP and divided into light, moderate, and severe groups by preoperative AHI. Friedman et al32 found that there was no significant difference in surgical success rate among the groups. In accordance with the criteria of postoperative AHI less than 20 and AHI decreased by 50% or more, patients were divided into success and failure groups. Differences in AHI, L-Sao2, CT90, and CT90% between the 2 groups were significant. Our previous study also showed that CT90 is a factor that affects surgical efficacy.15 These results suggest that disease severity is an important predictor of surgical outcome of UPPP for OSAHS. In the present study, all patients were divided into moderate and severe groups by preoperative AHI, but there was no significant difference between the 2 groups. However, the sample in present study was not large and the majority of patients belonged to the severe group. Thus, further studies are required with larger numbers of patients. We examined the effect of surgical method on efficacy and found that ZPPP and H-UPPP showed no significant difference in surgical outcome, which indicated that for patients with OSAHS and a narrow palatopharyngeal area, surgical method was not a major factor affecting efficacy. Thus, further studies are required with larger numbers of patients. In our study, 95% confidence intervals were in accord with P values of FBG, ApoE, HDL, CT90, and CT90%. These parameters, which had statistical significance, also had narrower 95% confidence intervals, so the results were reliable, although some false positives or negatives might arise because of 25 individual statistical comparisons of 2 groups or because of interference from other parameters. But other parameters such as AHI, L-Sao2, and MI had wide 95% confidence intervals and need to be verified by further studies. In conclusion, tongue position and tonsil size did not affect surgical outcome independently. However, the codetermined Friedman OSA stage, glucose and lipid metabolism factors, and disease severity may be important factors that affect surgical efficacy. Further studies are needed with larger numbers of patients to confirm these findings.
1053 Acknowledgments We thank Professor Song Yanyan for providing statistical support. Yuan Ping Xiong and Hong Liang Yi contributed equally to this study and should be regarded as co-first authors.
Author Contributions Yuan Ping Xiong, acquisition of data or analysis and interpretation of data, write and revise the manuscript; Hong Liang Yi, acquisition of data or analysis and interpretation of data and revise the manuscript; Shan Kai Yin, acquisition of data, revise and approve the final manuscript; Li Li Meng, acquisition of data, revise and approve the final manuscript; Xu Lan Tang, acquisition of data, revise and approve the final manuscript; Jian Guan, acquisition of data, revise and approve the final manuscript; Hui Ping Luo, acquisition of data, revise and approve the final manuscript; Wei Tian Zhang, contributions to conception and final approval of the version to be published. Bin Chen, contributions to conception and design, drafting the article, revising it critically for important intellectual content, and revising the manuscript.
Disclosures Competing interests: None. Sponsorships: None. Funding source: Program for Fitting and Proper Technology of Shanghai Shenkang Center (SHDC12010209), to conduct the study and to provide financial assistance in collection of the data.
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