Amali et. al. 2017[31]
Amali et. al. compared UPPP with radiofrequency ablation of the soft tissue in 40 patients with mild to moderate OSA in a randomized clinical trial. Patients with mild to moderate OSA (AHI >5 and AHI<30) with DISE findings suggesting velopharyngeal or oropharyngeal lateral wall collapse were included. BMI above 35, tongue base or epiglottis obstruction or severe comorbidities were reasons for exclusion. Patient baseline characteristics including clinical findings such as tonsil size, FTP, use of tobacco and blood pressure were reported. Detailed follow-up time was not reported, however the study states that follow-up was 6 months. Postoperative AHI, postoperative ESS and postoperative nadir O2 saturation was reported. Furthermore, all patients completed the Sleep Apnea Quality of Life Index questionnaire (SAQLI). Treatment success was defined as >50% reduction in AHI from baseline.
The study reported a statistically significant reduction in AHI in both groups (UPPP 10.12 (6.76; 13.48) (MRFTA 6.03 (2.77; 9.29)) and a statistically significant reduction in ESS (UPPP 5.20 (3.29; 7.11)) and (MRFTA 5.73 (2.99; 8.47)). Furthermore, they found a statistically significant improvement in mean SpO2 nadir in both groups. The postoperative AHI was significantly lower in the UPPP group compared to MRFTA group (p=0,02). Surgical success rate in the UPPP group was significantly higher than in the MRFTA group, 73% versus 40% (p=0,03). For ESS and mean SpO2 nadir they found no statistically significant differences between the two groups.
Quality of life reported with SAQLI improved in both groups and reported higher in MFRTA group in two domains including social interaction and treatment-related symptoms.
Hong et. al. 2019[32]
Hong et. al. reported a retrospective cohort study of 63 patients with OSA diagnosed with isolated lateral pharyngeal collapse during DISE. Patients diagnosed with moderate to severe OSA (35% and 65% respectively) underwent Expansion Sphincter Pharyngoplasty (ESPL) including bilateral tonsillectomy, removal of uvula mucosa and reduction of the uvula tip. All patients had nasal obstruction and received either turbinoplasty or combined septoturbinoplasty. Detailed follow-up time was not reported, however the study states that follow-up was 6 months. Postoperative AHI, postoperative ESS and postoperative SpO2 nadir was reported.
Patient selection was based upon DISE findings such as retropalatal circumferential narrowing above DISE grade II (more than 75% narrowing) and narrowed oropharynx due to lateral pharyngeal collapse of the bulky redundant soft tissue around the posterior pillars. The patients did not have obstruction at the tongue base or epiglottis. Clinical findings such as tonsil sizes, Friedman tongue position scale or neck circumferential were not reported, nor were patient baseline characteristics described.
The study reported a statistically significant reduction in AHI 18.20 (14.76; 21.64) and ESS 9.90 (7.87; 11.93). Limitations were the use of nasal surgery in all patients, however all patients had moderate to severe OSA, and nasal surgery is not considered to improve moderate to severe OSA, hence is not considered to be a part of multi-level sleep surgery.
Base of tongue:
Babademez et. al. 2019[33]
Babademez et. al. reported a prospective randomized study and comparison of robotic tongue base resection vs coblation tongue base resection. Patients with moderate to severe OSA reported by PSG, tonsil size 1-2 and BMI < 35 and isolated tongue base obstruction diagnosed during DISE preoperatively, were randomized in either robotic group (TORS) or coblation group. The randomization was done in the operating room. One surgeon performed all robotic treatments, and another surgeon performed all coblation treatments. Clinical findings were not reported; however, inclusion and exclusion parameters include clinical findings. Previous tonsillar surgery, limited mouth opening, and severe comorbidities were exclusion parameters. Seventy-seven patients were included and randomized to the study. Four patients were excluded due to perioperative complications of anesthesia. Three patients (two in TORS group and 1 in coblation group) were lost to follow-up. Follow-up time was 6 months. Post-operative AHI, ESS and snoring VAS were reported and compared to preoperative data. Operation time, time to oral diet in days and the length of analgesia needed postoperative were also reported.
The study reports a statistically significant reduction in mean AHI with a 36% reduction in TORS group (19.00 (15.84; 22.16)) and 37.8% reduction in coblation group (16.90 (14.33; 19.47)). A statistically significant reduction in ESS was also reported with 33.8% reduction in the TORS group (8.00 (6.94; 9.06) and 31.5% in the coblation group (7.80 (6.76; 8.84]). No statistically significant differences were seen between the two groups in any outcome parameters, however coblation was associated with quicker recovery and lower complication risks.
Strollo et. al. 2014[34]
The Stimulation Therapy for Apnea Reduction (STAR) trial presented by Strollo et. al. was pivotal regarding UAS therapy in patients with moderate to severe OSA. This led to FDA approval of the device and hence multiple studies have been published also in Europe with concurrent results. Strollo et. al. presents a multi-center prospective cohort study with 126 adult patients implanted with a unilateral hypoglossal nerve stimulator with a follow-up time of 12 months. Patients were carefully selected by inclusion criteria based upon previous feasibility studies. The first 46 consecutive patients after 12 months were randomized 1:1 and 23 patients were selected to a therapy-withdrawal group with deactivation of the implant and thereby used as a control group.
Primary outcomes were AHI and oxygen desaturation index (ODI) by PSG and secondary outcomes such as ESS and disease-specific quality of life assessed by the Functional Outcomes of Sleep Questionnaire (FOSQ) were reported. Patient baseline data and comorbidities, previous surgery such as uvulopalatopharyngoplasty and blood pressure were reported. Follow-up at two months and six months were performed but not stated. The implants were activated one month postoperatively. Surgical response was defined as Sher’s criteria at 12 month´s follow-up. Furthermore, surgical response was defined as at least 25% reduction in ODI and reported. Two patients were lost to follow-up and considered non-responders.
The study showed a statistically significant reduction in mean AHI of 16.70 (13.19; 20.21. Surgical responders based upon AHI were 83 of 126 patients (66%) and based upon ODI was 94 of 126 patients (75%). Mean ESS and mean FOSQ were also statistically significantly improved.
The therapy-withdrawal study showed a significant difference between the withdrawal group and the therapy-maintenance group with respect to the change in AHI from the beginning of the randomization to
the assessment 1 week later. In the withdrawal group, baseline AHI was 30,1 events per hour, before deactivation 7,6 events per hour and after deactivation 25,8 events per hour, whereas the maintenance group reported baseline AHI 31,3 events per hour, at randomization 7,2 events per hour and 1 week later 8,9 events per hour. Similar effects in ODI were reported in the study.
Adverse events were reported. Two patients had severe device-related adverse events which required repositioning and fixation of the neurostimulator. Other mild adverse events are also described in the study.
The study concludes that UAS showed a reduction in the severity of obstructive sleep apnea, and the adverse-event profile was acceptable. In 2018 5-year follow-up in the same group was published by Woodson et. al. (REF). Although only 71 patients had PSG at 5-year follow-up, the results were unchanged. Since the study is based upon the same group, the data is not included in this review.
Huntley et al. 2017[35]
Upper airway stimulation for treatment of OSA was also investigated by Huntley et. al and outcomes of two academic centers were compared. Patients from two different centers with 63 patients and 57 patients, respectively. Group 1 had a mean follow-up time of 90.39 days and group 2 had a mean follow-up time of 85.23 days. Although the study does not entirely fulfill the statement of minimum 3-month follow-up in this systematic review, the papers level of evidence is high and the study is the first non-industrial funded study with large number of patients, who have undergone UAS following the commercial availability of the device. Therefore, we found it compelling to include the study in the review.
Patients who completed postoperative PSG titration and outpatient follow-up were included in the study, which consisted of 48 patients and 49 patients respectively in the two groups. Baseline demographic data such as sex, age and BMI were reported. Baseline and postoperative AHI, ESS and SpO2 nadir were reported. Patients were included with the same criteria defined and published by Strollo et. al. (2014)[34] including DISE findings and the lack of concentric retropalatal collapse. Patient outcome from each group were analyzed individually and afterwards pooled. Surgical success followed Sher's criteria and defined as reduction of AHI > 50% and to a value of less than 20 events per hour.
The study showed statistically significant improvements in AHI (H-48 (29.54 (22.81; 36.27]) vs H-49 (29.01 24.39; 33.63)), ESS (H-48 (5.32 (3.89; 6.75)) and (H-49 (4.34 (1.97; 6.71)) and nadir O2 saturations in both groups, although the nadir O2 saturation in group 1 was better than in group 2. Surgical success was illustrated in the study’s figure 1 and reported around 90% of patients in both groups with no statistically significant differences between the two groups. The figure also illustrates the percentage of patients with AHI<15, AHI<10 and AHI<5 at each institution.
The study concluded that UAS is an effective alternative treatment in a subset of patients with moderate to severe OSA with base of tongue collapse, who were unable to comply with CPAP therapy.
Steffen 2018[36]
Upper airway stimulation of the hypoglossal nerve in patients with moderate to severe OSA has been investigated in a European setting by Steffen et. al. A multi-center prospective study with 60 patients in three German centers was conducted. Data from 6-month follow-up was reported by Heiser et. al. in 2016[37], however the latest report from Steffen et. al. is included in this review due to longer follow-up. Four patients did not complete the 12-month follow-up, one patient requested implant removal due to personal matters and three were lost to follow-up.
Patient baseline data such as age, BMI and sex were reported. Preoperative and postoperative therapy outcome AHI was reported using 2-night home sleep test. Follow-up was 6 months and 12 months after implantation. Implants were activated one month postoperatively. Two months after implantation, in-lab titration during PSG was performed to optimize the implant therapy. Primary outcomes were AHI postoperatively and secondary outcomes were ESS and Function Outcomes of Sleep Questionnaire (FOSQ) at 6 and 12 months. ODI, Sp02 nadir and mean SpO2 were also reported. Patients defined as surgical response and surgical success were also reported in line with Sher's criteria. The data was also compared to the STAR data reported by Strollo et. al. The study reported both mean and standard deviations, as well as median values with interquartile range. For comparison reasons, only mean values and SD values are reported in this review.
The study showed at statistically significant reduction in mean AHI 17.40 (12.38; 22.42) at 6-month follow-up and the improvement was unchanged at 12 month´s follow-up. Improvements in ODI, SpO2 nadir, mean ESS 6.30 (4.54; 8.06) and mean FOSQ was also statistically significant. At the end of the study, 30% of the patients were cured. 68% of the patients were considered as surgical responders. Patients lost to follow-up was regarded as non-responders. Comparison of surgical responders and non-responders showed no differences in baseline data such as age, BMI, neck circumference, AHI, ODI, FOSQ or ESS. The results were consistent with previous reported outcome by the STAR trial. The study concludes that UAS is a safe and feasible therapy capable to reduce OSA severity and prove patient reported quality of life outcomes, and therapy adherence was high after 12 months of follow-up.
Multi-level surgery:
Cammaroto et. al. 2018[38]
Cammaroto et. al. evaluated in a retrospective study both the influence of the volume of excised base of tongue on the surgical outcome after TORS and the role of the lymphatic or muscular predominance within the removed tissue. The premise for the study was a meta-analysis by Meccariello and Cammaroto showing promising results for TORS [39]. Although no correlations between the excised volume of the tongue base, the lymphatic/muscular ratio of removed tissue or total thickness of tongue base and AHI changes could be shown, the overall reduction in AHI in patients with moderate to severe OSA was reported and shown to be statistically significant 24.87 (19.31; 30.43).
The study consists of 51 patients who underwent single-step multi-level TORS including temporary tracheostomy, tonsillectomy, expansion sphincter pharyngoplasty and septoturbinoplasty and base of tongue excision. Patient characteristics such as age, gender, BMI, and preoperative and postoperative AHI were reported. Furthermore, mean tongue volume (cc), lymphatic/soft tissue ratio, total thickness of removed base of tongue and success rate were reported. Surgical response was defined accordingly to Sher's criteria.
No correlations were observed in postoperative AHI and anatomical measures of removed base of tongue tissue. Although the study did not show any differences in the primary measured outcomes, the observed reduction of AHI was found to be statistically significant and the rate of surgical success reported, concur with previous studies published.
El-Anwar et. al. 2018[40]
El-Anwar published a prospective non-randomized study with 40 patients scheduled for multilevel surgery. Surgery was multi-level surgery including hyoid suspension, tonsillectomy and pharyngeal suspension sutures described by El-Ahl and El-Anwar [41]. Group A consisted of patients with nasal obstruction and underwent inferior turbinate reduction), while group B did not. Postoperative follow-up was between 6 months and 14 months postoperatively. Patient baseline characteristics such as age, gender and BMI were reported. Primary outcome was AHI. Preoperative and postoperative data such as ESS and nadir oxygen saturation was also reported.
The preoperative and postoperative data was not tested within the groups. Between the groups, preoperative AHI was significantly higher in patients with nasal obstruction (group A) compared to patients with no nasal obstruction (group B) and the reduction in AHI was greater in group A than in group B (43.90 (31.83; 55.97) vs 23.30 (8.84; 37.76) respectively. No difference in the change in ESS between group A and B (8.50 (5.78; 11.22) and 8.60 (6.13, 11.07).
The study suggests that nasal obstruction, although not pivotal in treating OSA, is beneficial in a multi-level treatment setup, as the decrease in AHI in group A is larger than in group B. Unfortunately, the study setup is not optimal to investigate this question, since a group of patients with nasal obstruction without nasal surgery is lacking.
Thaler et. al 2016[42]
Thaler et. al. reported the effect of TORS in a prospective, non-randomized trial with historical controls, a study with 75 adult patients with moderate to severe OSA with AHI > 20, and who had failed CPAP. This study did not exclude patients with any prior airway surgery such as tonsillectomy or UPPP. The study did not have any maximum AHI or BMI. DISE was performed in all patients and patients with retro-lingual collapse underwent TORS. Patients with simultaneous retropalatal collapse were offered UPPP, if not performed previously. A historical cohort of previous UPPP surgery was used as comparison. All patients undergoing TORS and UPPP had both procedures as single-step surgery, TORS was performed first. Postoperative follow-up including PSG and ESS evaluation was done at a minimum of 3 months. Detailed follow-up time was not reported. Surgical response and surgical success rates were defined as Sher's criteria like other studies and reported. Patient baseline data were not reported. Preoperative and postoperative AHI, ESS and SpO2 nadir were also reported. Group 1 were 45 patients with no prior surgery and received TORS and UPPP surgery. Group 2 were 31 patients with prior surgery (tonsillectomy or UPPP).
The study found a statistically significant reduction in mean AHI in group A 38.90 (29.97; 47.83), whereas the decrease in AHI in group 2 (mean 10.00, (95% CI; 4.77; 24.77)) was not statistically significant. The improvements in SpO2 nadir was not statistically significant when each group was analyzed. When data was pooled, the improvements in AHI and SpO2 nadir were statistically significant. Looking at surgical response and surgical success, 25 patients (56%) in group 1 had surgical success, 8 patients (17%) with surgical response and 12 patients 27%) were considered as failures, while in group 2, nine patients (30%) had surgical success, three patients (10%) were responders, and 18 patients (60%) were failures.
The study concludes that TORS and UPPP is safe, and the results provide evidence in favor of multilevel approach, however there is still a significant percentage of patients for whom surgery does not improve OSA and therefore improved preoperative screening is necessary.