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 Table of Contents  
Year : 2023  |  Volume : 40  |  Issue : 1  |  Page : 37-42

Predictors of retitration in the sleep laboratory: Experience of a single center

1 Department of Neurology, Adnan Menderes University Faculty of Medicine, Ankara, Turkey
2 Department of Neurology, Division of Clinical Neurophysiology, Gazi University Faculty of Medicine, Ankara, Turkey

Date of Submission04-Aug-2022
Date of Decision07-Nov-2022
Date of Acceptance03-Dec-2022
Date of Web Publication29-Mar-2023

Correspondence Address:
Asli Akyol Gurses
Department of Neurology, Division of Clinical Neurophysiology, Faculty of Medicine, Gazi University, Besevler 06500, Ankara
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/nsn.nsn_141_22

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Background: Obstructive sleep apnea syndrome (OSAS) is a serious public health problem that causes a significant economic burden worldwide. Apart from several treatment approaches, positive airway pressure (PAP) therapy remains the gold standard. Performing an optimal manual titration study to explore the beneficial and comfortable pressure for patients is essential, but the process is troublous sometimes, requiring multiple attempts. The objective of this study was to present our single-center experience regarding PAP titration studies in OSAS and identify the clinical and laboratory parameters that might predict repeat titration. Materials and Methods: Medical charts of 248 patients with OSAS who were eligible for PAP therapy were retrospectively reviewed. Age, sex, body mass index, modified Mallampati scores, presence of positive Muller maneuvers, and polysomnographic parameters yielded from diagnostic studies were recorded and compared between patients with single versus repeat titrations. Results: The mean age, the proportion of males, and the rate of patients with positive Muller maneuvers were significantly increased in the retitration group (P = 0.015, P = 0.022, and P = 0.001, respectively). Multivariate regression analysis revealed that age and positive Muller maneuvers were independent associates of repeat titration (P = 0.036 and P = 0.005, respectively). Conclusion: Our results suggest that both aging and the presence of a positive Muller maneuver may predict a troublous titration study, raising the need for recurrent attempts. The final common pathway could contribute to a vulnerable and more collapsible airway during sleep. Recognizing the potential need for retitration at the beginning is favorable regarding adjustment of the laboratory conditions and increases the patients' adherence during the management course. The results also confirm the capability of manual titration in terms of exploring proper PAP pressures in the majority of patients with OSAS.

Keywords: Manual titration, obstructive sleep apnea syndrome, positive airway pressure therapy, predictor, retitration

How to cite this article:
Akyildiz UO, Gurses AA. Predictors of retitration in the sleep laboratory: Experience of a single center. Neurol Sci Neurophysiol 2023;40:37-42

How to cite this URL:
Akyildiz UO, Gurses AA. Predictors of retitration in the sleep laboratory: Experience of a single center. Neurol Sci Neurophysiol [serial online] 2023 [cited 2023 Jun 10];40:37-42. Available from: http://www.nsnjournal.org/text.asp?2023/40/1/37/372782

  Introduction Top

Obstructive sleep apnea syndrome (OSAS) is characterized by recurrent obstructions of the upper airway during sleep, either in whole or in part, with subsequent desaturation and/or arousals. Typical symptomatology includes snoring, witnessed apnea, and excessive daytime sleepiness. The diagnosis can be made in the presence of clinical symptoms together with polysomnographic evidence of at least five dominantly obstructive respiratory events per hour, including apneas, hypopneas, and respiratory effort-related arousals (respiratory disturbance index [RDI] ≥5) or a diagnostic study indicating RDI ≥15/h.[1] Obesity is the major risk factor and most frequent companion. However, the list of comorbidities is much longer, including hypertension, metabolic syndrome, coronary artery disease, arrhythmias, cerebrovascular events, and pulmonary hypertension, and the direction of the cause-effect relationship is not definite every time.[2],[3],[4] The estimated prevalence, which approximates 3%–7% among men and 2%–5% among women,[5] is considerably high, and diagnostic or therapeutic processes require high technical equipment together with qualified staff. Taken together, OSAS causes a significant economic burden worldwide, besides being a serious public health problem.

Apart from several methods, including conservative approaches, oral devices, or surgical interventions, positive airway pressure (PAP) therapy remains the gold-standard treatment.[6] Therefore, the identification of appropriate and well-tolerated PAP pressure that eliminates respiratory events is vital. Achieving this goal in the first attempt is the primary aim of sleep physicians and technicians. However, the need for repeat titration studies is not rare and has a rationale because most patients have a determinable pressure beneficial for respiratory events and comfortable for use. The objective of this study was to present our single-center experience regarding PAP titration studies in OSAS and identify the clinical and laboratory parameters that might predict repeat titration (retitration) studies.

  Materials and Methods Top


The medical records of patients who were evaluated with at least one of the following symptoms: snoring, witnessed apnea, and excessive daytime sleepiness between June 2017 and February 2019 in a single center and who were identified as eligible candidates for PAP therapy after the diagnosis of OSAS following one-night diagnostic polysomnography in the sleep laboratory were retrospectively reviewed. Patients who were to undergo a conservative approach consisting of weight loss, altering sleep position, and limiting sedative agents, and those who refused PAP therapy were excluded from the study. Two hundred and forty-eight patients were included in the study [Figure 1]. Age, sex, height, weight, body mass index (BMI), and symptom duration were recorded for every patient, and all were screened for excessive daytime sleepiness using the Epworth Sleepiness Scale. After a detailed sleep history and physical-neurologic examination, our routine procedure of the first visit included pulmonary function tests and chest examination to examine for preexisting lung disease, and otorhinolaryngologic (ear-nose-throat) examinations, including Muller maneuvers to check for visible structural pathologies that could result in anatomic obstruction through the upper airway. The findings of Muller maneuvers, which assess the level (retropalatal-retrolingual), and the degree of collapsibility of the upper airway through flexible endoscope in the sitting position during reverse Valsalva maneuvers were presented as positive or negative.[7] The clinical (demographic and anatomic) and laboratory parameters that could influence the performance of the initial titration study were investigated. Modified Mallampati scores and the presence of positive Muller maneuvers as “anatomic” parameters and data obtained from diagnostic polysomnography (level of OSAS, snore percentage, average spO2, duration of time spent SPO2 <90%, oxygen desaturation index, minimum spO2 [%], dependence of rapid eye movement [REM], and sleep position) as “laboratory” parameters were also examined for each patient. The study protocol was approved by the Local Ethics Committee.
Figure 1: A summary of the study population and the results. PSG: Polysomnography, OSAS: Obstructive sleep apnea syndrome, PAP: Positive arway pressure

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Diagnostic study

The Nox Medical programme was used for recording all-night polysomnographic studies and included an electrooculogram, six-channel electroencephalogram, electrocardiogram, chin and leg electromyogram, thoracic and abdominal respiratory effort, oronasal thermal and nasal airflow, pulse oximetry, and body position. All polysomnographic data were subjected to a manual scoring by the same certified clinical neurophysiologist according to the American Academy of Sleep Medicine (AASM) 2014 v2.4 guidelines and supervised by another sleep specialist. A respiratory event was scored as apnea when there was ≥90% diminution of baseline airflow (signal) amplitude for minimum 10 s. Hypopnea was scored in cases of a ≥30% decrease of preevent airflow amplitude lasting for a minimum of 10 s in the presence of ≥3% oxygen desaturation or arousal in association with the event.[8] The apnea–hypopnea index (AHI) was calculated as the sum of apneas and hypopneas per hour of sleep. Patients with an AHI value of ≥5 and <15 were diagnosed as having mild OSAS, ≥15 and <30 as moderate OSAS, and ≥30 as severe OSAS.

Titration study

Manual PAP titration studies were performed by the same team on a separate night from the diagnostic night following the recommendations of the PAP Titration Task Force of the AASM to achieve an optimal or good or adequate titration.[9] In the case of a study that did not suit the criteria of these three grading levels, it was classified as an “unacceptable” titration necessitating a repeat study. In our laboratory, we pay a particular attention to exploring the pressure required for the maintenance of sufficient supine REM sleep; therefore, some adequate studies were also repeated.

Statistical analyses

Statistical analyses were conducted using the IBM SPSS ver. 20 (SPSS, Inc., Chicago, Illinois, USA) package program. The normality of the data distribution was examined using the Shapiro-Wilk test. Numerical data are presented as mean ± standard deviation or median (minimum–maximum). Categorical variables are presented as percentages. Continuous parameters were compared using the Student's t-test or the Mann–Whitney U test according to the normality of data distribution. For the comparison of categorical variables, the Chi-square test was used. A multiple regression model was used for the identification of independent predictors. A two-tailed P < 0.05 was accepted as statistically significant.

  Results Top

The median age was 53 (range, 22–82) years, and the median BMI was 32.1 (range, 16.9–65.3) kg/m2 in our study population. One hundred and seventy-one (69%) patients were male, and the remaining 31% (n = 77) were female. The majority (67%) of the patients had severe OSA; 27% had moderate and 6% had mild OSA. A constant PAP pressure could be prescribed in 153 out of 248 patients (62%) following the first titration night. Ninety-five (38%) patients required repeat titration, mostly due to a lack of a sufficient supine REM phase. The other reasons for repeat titration were inadequate sleep efficiency, patient incompatibility, inability to reach the desired pressure, and the requirement to switch from continuous positive airway pressure (CPAP) to bilevel positive airway pressure (BPAP) titration due to high-pressure need or patient intolerance (in the absence of enough time or eligible device for the first treatment night). The results of our final studies revealed that 59% satisfied “optimal,” 35% “good,” and 6% “adequate” titration criteria according to the AASM Task Force.[9]

Patients who necessitated a repeat study were further analyzed in terms of clinical (demographic and anatomic) and laboratory parameters. The relative parameters were then compared between patients with single titration and repeat titration studies [Table 1].
Table 1: Demographic, anatomic, and polysomnographic findings of the study population regarding titration recurrence

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The mean age in the single titration group was 50.08 ± 12.02 years, the median BMI was 32 (range, 19–60.2) kg/m2, and the corresponding values were 54.08 ± 13.31 years and 33.1 (range, 16.9–65.3) kg/m2 in the retitration group (P = 0.015* and P = 0.704, respectively). The proportion of men was significantly higher in the retitration group (64% vs. 78%, P = 0.022*). The median modified Mallampati scores were both 4 (range, 1–4) within the two groups (P = 0.335); however, the rate of positive Muller maneuvers was significantly higher in the retitration group (47% in the single group vs. 74% in the retitration group) (P = 0.001*). OSA severity was similar between the two groups (67% severe, 28% moderate, and 5% mild OSA in the single titration group vs. 66% severe, 25% moderate, and 9% mild OSA in the retitration group) (P = 0.445), as were AHI, snore percentage, and parameters of oxygen saturation obtained from diagnostic polysomnographic studies (P > 0.05). The proportion of REM (18% for single titration vs. 15% for repeat titrations) (P = 0.526) and position-dependent OSAS (31% for single titration vs. 28% for repeat titration) (P = 0.663) were also similar between the two groups.

Univariate regression analyses indicated significance for the male sex, increased age, and positive Muller maneuvers; however, a multivariate regression model was significant for age and positive Muller maneuvers only, which demonstrated an independent association with retitration [Table 2]. The mean age and the distribution of OSA severity demonstrated no significant difference between patients with positive and negative Muller maneuvers (P = 0.057 and P = 0.053, respectively).
Table 2: Regression analysis regarding the independent associates of repeat titration

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A summary of our PAP treatment experience showed that 73% of the patients were prescribed CPAP, whereas 23% required BPAP (due to a diagnosis of chronic obstructive pulmonary disease or need for high pressure during CPAP titration) and 4% were treated with autoCPAP.

  Discussion Top

Despite advances in various oral appliances and surgical methods, PAP therapy is still the gold-standard treatment for OSAS.[6] Variable compliance rates between 32% and 87% could be discouraging for physicians sometimes;[10] however, identifying the ideal pressure for a patient that abolishes respiratory events and enables comfortable use, overcomes this issue to a large extent. Therefore, performing an optimal, or at least an adequate titration study, should be the primary target of sleep physicians and technicians. Achieving this goal in the first attempt is essential; nevertheless, the need for repeat studies is not rare. Prediction of this recurrence in the diagnostic phase would be beneficial for the patient, the health-care team, and the sleep laboratory.

In the current study, we demonstrated that increased age and positive Muller maneuvers were independent associates of recurrent titration. The Muller maneuver is an awake endoscopic assessment that visualizes the upper airway and discloses the potential obstruction levels and degrees inside. It has been used frequently in presurgical planning in OSAS for years.[11] Although some reports suggested a correlation between Muller's findings and OSAS severity,[12] others failed to demonstrate such a relationship.[13] In our cohort, OSAS severity and age were similar between patients with positive and negative Muller maneuvers.

Increased age was demonstrated to be the other independent associate of retitration. Age is also a well-defined risk factor for OSAS. Either remodeling of bony structures and soft tissue around the pharynx or insufficient functioning of the pharyngeal dilator muscles with concomitant aging seems to result in a narrower airway that easily collapses under challenging circumstances such as sleep and decreased muscle tone.[14] As a common final pathway, both aging and the presence of a positive Muller maneuver seem to contribute to a vulnerable upper airway prone to collapse and one that is hard to handle during initial titration studies, which raises the need for a second and maybe third studies.

Our results also confirmed the capability of manual titration in terms of identifying a fixed CPAP pressure for individuals with OSAS. Despite some recent papers reporting the comparable rates of CPAP acceptance and AHI improvement following autotitration,[15] manual titration still seems to be the ideal technique to explore an optimal pressure that also maintains an adequate supine REM sleep (critical step for an optimal and good titration), and making a decision based on a pressure profile of the 90th or 95th percentile of an autotitration night may not always satisfy the patients' needs.[16],[17] In the same way, autoCPAP devices are not sine qua non in the management of OSAS because the effect on posttreatment AHI, subjective sleepiness, and adherence issues is similar to the standard CPAP.[18] A standard CPAP pressure could be explored even in the majority of cases with REM and position-dependent OSA following a proper titration study that matches the guideline recommendations.

We repeated some of the adequate studies which might result in relatively higher rates of retitration because we expended a considerable effort in exploring the appropriate pressure for the maintenance of sufficient supine REM sleep. This could be counted as a limitation of the current study. However, supine REM sleep seems to be the most challenging sleep period in patients with OSAS due to the deteriorating effects of both REM sleep and supine position on respiratory events, and overcoming this issue may improve a long-term PAP adherence.

  Conclusion Top

Troublous titration and the need for repeat studies could be predicted during the initial assessment. Performing the initial titration study of patients with increased age and positive Muller maneuvers on a multimodal PAP device may avoid recurrent admissions, at least for certain circumstances such as the requirement of a CPAP-BPAP switch due to a need for high pressure. Furthermore, informing the relevant patients about the possibility of recurrent studies at the beginning could prevent further losses to follow-up.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

  References Top

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Pavwoski P, Shelgikar AV. Treatment options for obstructive sleep apnea. Neurol Clin Pract 2017;7:77-85.  Back to cited text no. 6
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American Academy of Sleep Medicine Task Force. Sleep-related breathing disorders in adults: Recommendations for syndrome definition and measurement techniques in clinical research. The Report of an American Academy of Sleep Medicine Task Force. Sleep 1999;22:667-89.  Back to cited text no. 8
Kushida CA, Chediak A, Berry RB, Brown LK, Gozal D, Iber C, et al. Positive airway pressure titration task force of the american academy of sleep medicine clinical guidelines for the manual titration of positive airway pressure in patients with obstructive sleep apnea. J Clin Sleep Med 2008;4:157-71.  Back to cited text no. 9
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Schwartz RN, Payne RJ, Forest VI, Hier MP, Fanous A, Vallée-Gravel C. The relationship between upper airway collapse and the severity of obstructive sleep apnea syndrome: A chart review. J Otolaryngol Head Neck Surg 2015;44:32.  Back to cited text no. 12
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Gao W, Jin Y, Wang Y, Sun M, Chen B, Zhou N, et al. Is automatic CPAP titration as effective as manual CPAP titration in OSAHS patients? A meta-analysis. Sleep Breath 2012;16:329-40.  Back to cited text no. 15
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  [Figure 1]

  [Table 1], [Table 2]


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