Evidence of Nasal Cooling and Sensory Impairments Driving Patient Symptoms With Septal Deviation.

OBJECTIVES/HYPOTHESIS: About 260,000 septoplasties are performed annually in the US to address nasal septal deviation (NSD). Yet, we do not consistently understand what aspects of NSD result in symptoms. STUDY DESIGN: Blinded cohort study. METHODS: Two fellowship-trained surgeons blindly reviewed computerized tomography (CTs) of 10 confirmed NSD patients mixed with 36 healthy controls. All patients were correctly identified, however, 24/36 controls were falsely identified by both surgeons as patients (33.3% specificity), which were grouped as asymptomatic NSD (aNSD), while the remaining controls as non-NSD (healthy). Acoustic rhinometry, rhinomanometry, individual CT-based computational fluid dynamics and nasal sensory testing were applied to address the puzzling questions of why these aNSD had no symptoms and, more fundamentally, what caused symptoms in sNSD patients. RESULTS: aNSD reported no nasal symptoms - Nasal Obstruction Symptom Evaluation score (sNSD: 60.50 ± 13.00; aNSD: 5.20 ± 5.41; non-NSD: 6.66 ± 7.17, P < .05); 22-item Sino-Nasal Outcome Test score (sNSD: 32.60 ± 14.13; aNSD: 10.04 ± 10.10; non-NSD: 9.08 ± 12.42, P < .001). No significant differences in measured nasal resistance, minimum cross-sectional area (MCA), degree of septal deviation, and nasal airflow distributions were found between sNSD and aNSD groups. Only three variables differentiate sNSD versus aNSD: anterior averaged heat flux on deviated side, inferior turbinate peak heat flux on non-deviated side, and nasal cool sensitivity measured by menthol lateralization threshold, with no significant differences among these variables found between the two healthy groups (aNSD vs. non-NSD). These variables by themselves or combined can differentiate sNSD from controls with higher specificity than the physicians (ROC area under the curve = 0.84 with 70% sensitivity and 91.6% specificity). CONCLUSIONS: This study sheds light on the potential mechanisms of NSD symptomatology: distorted nasal cooling due to NSD exacerbated by poorer nasal mucosal sensitivity. It further supports our previous hypothesis that nasal obstruction complaints do not result directly from obstruction, rather from the capacity of our nose to subjectively sense airflow cooling. LEVEL OF EVIDENCE: 3 Laryngoscope, 132:509-517, 2022.

Computational modeling of nasal nitric oxide flux from the paranasal sinuses: Validation against human experiment.

BACKGROUND: Nitric oxide (NO) is important in respiratory physiology and airway defense. Although the paranasal sinuses are the major source of nasal NO, transport dynamics between the sinuses and nasal cavities are poorly understood. METHODS: Exhaled nasal NO tracings were measured in two non-asthmatic subjects (one with allergic rhinitis, one without) using NO analyzer connected via face mask. We subsequently performed computational fluid dynamics NO emission simulations based on individual CT scans and compared to the experimental data. RESULTS: Simulated exhaled NO tracings match well with experimental data (r > 0.84, p < 0.01) for both subjects, with measured peaks reaching 319.6 ppb in one subject (allergic-rhinitis), and 196.9 ppb in the other. The CFD simulation accurately captured the peak differences, even though the initial sinus NO concentration for both cases was set to the same 9000 ppb based on literature value. Further, the CFD simulation suggests that ethmoid sinuses contributed the most (>67%, other sinuses combined <33%) to total nasal NO emission in both cases and that diffusion contributes more than convective transport. By turning off diffusion (setting NO diffusivity to ~0), the NO emission peaks for both cases were reduced by >70%. CONCLUSION: Historically, nasal NO emissions were thought to be contributed mostly by the maxillary sinuses (the largest sinuses) and active air movement (convection). Here, we showed that the ethmoid sinuses and diffusive transport dominate the process. These findings may have a substantial impact on our view of nasal NO emission mechanisms and sinus physiopathology in general.

Regional Peak Mucosal Cooling Predicts Radiofrequency Treatment Outcomes of Nasal Valve Obstruction.

OBJECTIVES/HYPOTHESIS: Low energy radiofrequency may offer effective treatment for narrow or obstructed nasal valve, yet its precise mechanism is not fully understood. STUDY DESIGN: Prospective, nonrandomized, case series. METHODS: Twenty prospective patients with internal nasal valve obstruction underwent office-based Vivaer treatment (Aerin Medical, Inc) under local anesthesia. Computational fluid dynamics (CFD) models were constructed based on the pre- and 90 days post-procedure computed tomography (CT) scans to identify salient changes in nasal airflow parameters. RESULTS: Patients' Nasal Obstruction Symptom Evaluation score (NOSE: pre-treatment 78.89 ± 11.57; post-treatment 31.39 ± 18.30, P = 5e-7) and Visual Analog Scale of nasal obstruction (VAS: pre-treatment 6.01 ± 1.83; post-treatment 3.44 ± 2.11, P = 1e-4) improved significantly at 90 days after the minimally invasive approach. Nasal airway volume in the treatment area increased ~7% 90 days post-treatment (pre-treatment 5.97 ± 1.20, post-treatment 6.38 ± 1.50 cm3 , P = .018), yet there were no statistically significant changes in the measured peak nasal inspiratory flowrate (PNIF, pre-treatment: 60.16 ± 34.49; post-treatment: 72.38 ± 43.66 ml/s; P = .13) and CFD computed nasal resistance (pre-treatment: 0.096 ± 0.065; post-treatment: 0.075 ± 0.026 Pa/(ml/s); P = .063). As validation, PNIF correlated significantly with nasal resistance (r = 0.47, P = .004). Among all the variables, only the peak mucosal cooling posterior to the nasal vestibule significantly correlated with the NOSE at baseline (r = -0.531, P = .023) and with post-treatment improvement (r = 0.659, P = .003). CONCLUSION: Minimal remodeling of the nasal valve (7% in this study) may have a profound effect on perceived nasal obstruction, despite little effect on nasal resistance, or PNIF. The results corroborated our previous findings that subjective relief of nasal obstruction correlates with regional mucosal cooling rather than nasal resistance or peak flow rate, a potential target for future effective, personalized therapeutic approaches. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:E1760-E1769, 2021.

Peak Sinus Pressures During Sneezing in Healthy Controls and Post-Skull Base Surgery Patients.

OBJECTIVES/HYPOTHESIS: Patients are frequently advised to sneeze with an open mouth and avoid nose-blowing following an endoscopic endonasal approache (EEA) to the skull base, despite a lack of quantitative evidence. This study applies computational fluid dynamics (CFD) to quantify sinus pressures along the skull base during sneezing. STUDY DESIGN: Case-control series. METHODS: Computed tomography or magnetic resonance imaging scans of four post-EEA patients and four healthy controls were collected and analyzed utilizing CFD techniques. A pressure drop of 6,000 Pa was applied to the nasopharynx based on values in the literature to simulate expiratory nasal airflow during sneezing. Peak pressures along the skull base in frontal, ethmoid, and sphenoid sinuses were collected. RESULTS: Significant increases in skull base peak pressure was observed during sneezing, with significant individual variations from 2,185 to 5,685 Pa. Interestingly, healthy controls had significantly higher pressures compared to post-EEA patients (5179.37 ± 198.42 Pa vs. patients 3,347.82 ± 1,472.20 Pa, P < .05), which could be related to higher anterior nasal resistance in unoperated healthy controls (0.44 ± 0.22 vs. 0.31 ± 0.16 Pa/mL/sec for patients, P = .38). The sinus pressure buildup may be due to airway resistance functioning as a valve preventing air from being released quickly. Supporting this theory, there was a strong correlation (r = 0.82) between peak skull base pressure and the ratio of anterior resistance to total resistance. Within-subject variation in pressures between different skull base regions was much lower (average = ~5%). CONCLUSIONS: This study provided the first quantitative analysis of air pressure along the skull base during sneezing in post-EEA patients through CFD, suggesting that pressure buildup may depend on individual anatomy. LEVEL OF EVIDENCE: 3b Laryngoscope, 130:2138-2143, 2020.

Computational fluid dynamic analysis of aggressive turbinate reductions: is it a culprit of empty nose syndrome?

BACKGROUND: Empty nose syndrome (ENS) remains highly controversial, with aggressive inferior turbinate reduction (ITR) or mucociliary dysfunction frequently implicated. However, the appropriate degree of ITR is highly debatable. METHODS: We applied individual computed tomography (CT)-based computational fluid dynamics (CFD) to 5 patients receiving relatively aggressive ITR but with no ENS symptoms, and compared them to 27 symptomatic ENS patients who all had histories of aggressive ITRs, and 42 healthy controls. Patients' surgical outcomes were confirmed with 22-item Sino-Nasal Outcome Test (SNOT-22) (ITR: 6.40 ± 4.56; ENS: 58.2 ± 15.9; healthy: 13.2 ± 14.9), Nasal Obstruction Symptom Evaluation (NOSE) scores (ITR: 4.00 ± 2.24; ENS: 69.4 ± 17.1; healthy: 11.9 ± 12.9), and Empty Nose Syndrome 6-Item Questionnaire (ENS6Q) (≥11 for ENS). RESULTS: Both aggressive ITR without ENS symptoms and symptomatic ENS patients had significantly lower nasal resistance (ITR: 0.059 ± 0.020 Pa·s/mL; ENS: 0.052 ± 0.015 Pa·s/mL; healthy: 0.070 ± 0.021 Pa·s/mL) and higher cross-sectional areas surrounding the inferior turbinate (ITR: 0.94 ± 0.21 cm2 ; ENS: 1.19 ± 1.05 cm2 ; healthy: 0.42 ± 0.22 cm2 ) than healthy controls. The lack of significant differences among patient groups indicated similar degrees of surgeries between ITR with and without ENS symptom cohorts. However, symptomatic ENS patients have paradoxical significantly less airflow in the inferior meatus (ITR: 47.7% ± 23.6%; ENS: 25.8% ± 17.6%; healthy: 36.5 ± 15.9%; both p < 0.01), but higher airflow around the middle meatus (ITR: 49.7% ± 22.6%; ENS: 66.5% ± 18.3%; healthy: 49.9% ± 15.1%, p < 0.0001) than aggressive ITR without symptoms and controls. Aggressive ITR patients have increased inferior meatus airflow as expected (p < 0.05). This imbalanced airflow produced less inferior wall-shear-stress distribution among symptomatic ENS patients only (ITR: 42.45% ± 11.4%; ENS: 32.2% ± 12.6%; healthy: 49.7% ± 9.9%). ENS patients (n = 12) also had impaired nasal trigeminal function, as measured by menthol lateralization detection thresholds (ITR: 15.2 ± 1.2; ENS: 10.3 ± 3.9; healthy: 13.8 ± 3.09, both p < 0.0001). Surprisingly, aggressive ITR patients without ENS symptoms have better menthol lateralization detection thresholds (LDTs) than healthy controls. CONCLUSION: Although turbinate tissue loss is linked with ENS, the degree of ITR that might distinguish postoperative patient satisfaction in their nasal breathing vs development of ENS symptoms is unclear. Our results suggest that a combination of distorted nasal aerodynamics and loss of mucosal sensory function may potentially lead to ENS symptomology.

Asymptomatic vs symptomatic septal perforations: a computational fluid dynamics examination.

BACKGROUND: A nasal septal perforation (NSP) can lead to frustrating symptoms for some patients while remaining completely asymptomatic for others, without a clear mechanism differentiating them. METHODS: We applied individual computed tomography (CT)-based computational fluid dynamics (CFD) to examine the nasal aerodynamics differences between 5 asymptomatic and 15 symptomatic NSP patients. Patients' symptoms were confirmed through interviews, 22-item Sino-Nasal Outcome Test score (asymptomatic, 25 ± 18.8; symptomatic, 53.7 ± 18.2), nasal obstruction symptom evaluation score (asymptomatic, 28.0 ± 32.1; symptomatic, 62.2 ± 32.2), and review of medical history. RESULTS: No statistical differences were found in perforation location, size (asymptomatic, 1.94 ± 1.88 cm2 ; symptomatic, 1.36 ± 1.44 cm2 ), nasal resistance (asymptomatic, 0.059 ± 0.012 Pa·s/mL; symptomatic, 0.063 ± 0.022 Pa·s/mL), and computed flow rate shunting across the perforation (asymptomatic, 52.9 ± 30.9 mL/s; symptomatic, 27.4 ± 23.6 mL/s; p > 0.05). However, symptomatic patients had significantly higher wall shear stress (WSS) and heat flux, especially along the posterior perforation margin (WSS, 0.54 ± 0.12 vs 1.15 ± 0.49 Pa, p < 0.001; heat flux, 0.21 ± 0.05 vs 0.37 ± 0.14 W/cm2 , p < 0.01). A WSS cutoff at 0.72 Pa can separate asymptomatic vs symptomatic NSP with 87% sensitivity and 100% specificity. Flow visualization showed flow peaks toward the posterior margin that may be responsible for the high WSS and heat flux among symptomatic NSPs. CONCLUSION: This study is the first CFD examination of asymptomatic and symptomatic NSP with regional aerodynamics and stress abnormalities, beyond size or location, being implicated as the mechanism behind the symptomology of NSP. This finding could serve as an objective basis for future personalized treatment decisions and optimization.

Computational fluid dynamics after endoscopic endonasal skull base surgery-possible empty nose syndrome in the context of middle turbinate resection.

BACKGROUND: Empty nose syndrome (ENS) is a rare and debilitating disease with a controversial definition, etiology, and treatment. One puzzling fact is that patients who undergo an endoscopic endonasal approach (EEA) often have resection of multiple anatomic structures, yet seldom develop ENS. In this pilot study, we analyzed and compared the computational fluid dynamics (CFD) and symptoms among post-EEA patients, ENS patients, and healthy subjects. METHODS: Computed tomography scans of 4 post-EEA patients were collected and analyzed using CFD techniques. Two patients had significant ENS symptoms based on results of the Empty Nose Syndrome 6-item Questionnaire (score >11), whereas the other 2 were asymptomatic. As a reference, their results were compared with previously published CFD results of 27 non-EEA ENS patients and 42 healthy controls. RESULTS: Post-EEA patients with ENS symptoms had a similar nasal airflow pattern as non-EEA ENS patients. This pattern differed significantly from that of EEA patients without ENS symptoms and healthy controls. Overall, groups with ENS symptoms exhibited airflow dominant in the middle meatus region and a significantly lower percentage of airflow in the inferior turbinate region (EEA with ENS, 17.74 ± 4.00% vs EEA without ENS, 51.25 ± 3.33% [t test, p < 0.02]; non-EEA ENS, 25.8 ± 17.6%; healthy subjects, 36.5 ± 15.9%) as well as lower peak wall shear stress (EEA with ENS, 0.30 ± 0.13 Pa vs EEA without ENS, 0.61 ± 0.03 Pa [p = 0.003]; non-EEA ENS, 0.58 ± 0.24 Pa; healthy subjects, 1.18 ± 0.81 Pa). CONCLUSION: These results suggest that turbinectomy and/or posterior septectomy may have a varying functional impact and that ENS symptoms go beyond anatomy and correlate with aerodynamic changes. The findings open the door for CFD as a potential objective diagnosis tool for ENS.

Nasal Structural and Aerodynamic Features That May Benefit Normal Olfactory Sensitivity.

Nasal airflow that effectively transports ambient odors to the olfactory receptors is important for human olfaction. Yet, the impact of nasal anatomical variations on airflow pattern and olfactory function is not fully understood. In this study, 22 healthy volunteers were recruited and underwent computed tomographic scans for computational simulations of nasal airflow patterns. Unilateral odor detection thresholds (ODT) to l-carvone, phenylethyl alcohol (PEA) and d-limonene were also obtained for all participants. Significant normative variations in both nasal anatomy and aerodynamics were found. The most prominent was the formation of an anterior dorsal airflow vortex in some but not all subjects, with the vortex size being significantly correlated with ODT of l-carvone (r = 0.31, P < 0.05). The formation of the vortex is likely the result of anterior nasal morphology, with the vortex size varying significantly with the nasal index (ratio of the width and height of external nose, r = -0.59, P < 0.001) and nasal vestibule "notch" index (r = 0.76, P < 0.001). The "notch" is a narrowing of the upper nasal vestibule cartilage region. The degree of the notch also significantly correlates with ODT for PEA (r = 0.32, P < 0.05) and l-carvone (r = 0.33, P < 0.05). ODT of d-limonene, a low mucosal soluble odor, does not correlate with any of the anatomical or aerodynamic variables. The current study revealed that nasal anatomy and aerodynamics might have a significant impact on normal olfactory sensitivity, with greater airflow vortex and a narrower vestibule region likely intensifying the airflow vortex toward the olfactory region and resulting in greater olfactory sensitivity to high mucosal soluble odors.

Investigation of the abnormal nasal aerodynamics and trigeminal functions among empty nose syndrome patients.

BACKGROUND: Abnormal nasal aerodynamics or trigeminal functions have been frequently implicated in the symptomology of empty nose syndrome (ENS), yet with limited evidence. METHODS: Individual computed tomography (CT)-based computational fluid dynamics (CFD) was applied to 27 ENS patients to simulate their nasal aerodynamics and compared with 42 healthy controls. Patients' symptoms were confirmed with Empty Nose Syndrome 6-item Questionnaire (ENS6Q), 22-item Sino-Nasal Outcome Test (SNOT-22), and Nasal Obstruction Symptom Evaluation (NOSE) scores. Nasal trigeminal sensitivity was measured with menthol lateralization detection thresholds (LDTs). RESULTS: ENS patients had significantly lower (∼25.7%) nasal resistance and higher (∼2.8 times) cross-sectional areas compared to healthy controls (both p < 0.001). Despite inferior turbinate reductions, CFD analysis demonstrated that ENS patients had increased airflow concentrated in the middle meatus region (66.5% ± 18.3%) compared to healthy controls (49.9% ± 15.1%, p < 0.0001). Significantly less airflow (25.8% ± 17.6%) and lower peak wall shear stress (WSS) (0.58 ± 0.24 Pa) were found in the inferior meatus (vs healthy: 36.5% ± 15.9%; 1.18 ± 0.81 Pa, both p < 0.05), with the latter significantly correlated with the symptom scores of ENS6Q (r = -0.398, p = 0.003). Item-wise, complaints of "suffocation" and "nose feels too open" were also found to be significantly correlated with peak WSS around the inferior turbinate (r = -0.295, p = 0.031; and r = -0.388, p = 0.004, respectively). These correlations were all negative, indicating that less air-mucosal stimulations resulted in worse symptom scores. ENS patients (n = 12) also had impaired menthol LDT when compared to healthy controls (p < 0.0001). CONCLUSION: This is the first CFD examination of nasal aerodynamics in a large cohort of ENS patients. The results indicated that a combination of loss of neural sensitivity and poorer inferior air-mucosal stimulation may potentially lead to ENS symptomology.

Computational fluid dynamics evaluation of posterior septectomy as a viable treatment option for large septal perforations.

BACKGROUND: Numerous surgical techniques exist to treat nasal septal perforation (NSP). The surgical closure of large NSPs (>2 cm) is still challenging. Posterior septectomy has been reported as a simple alternative to treat large NSP, yet its mechanisms for symptom relief are not clear, and if failed, its consequence cannot be easily reversed. METHODS: Ten NSP patients were recruited: 5 underwent posterior septectomy and 5 underwent conventional flap or button repair. Computational fluid dynamics (CFD) simulated the nasal aerodynamics based on computed tomography (CT) scans. All patients had preoperative CT; however, only 4 had postoperative CT: 2 underwent posterior septectomy and the other 2 underwent flap repair. We examined surgical outcomes and the nasal airflow features among the 2 treatment options. RESULTS: Both groups of patients had good outcomes based on chart review. Patients undergoing septectomy had significantly larger perforation size (2.32 ± 0.87 vs 1.21 ± 0.60 cm), higher flow rate across the perforation (47.8 ± 28.6 vs 18.3 ± 12.2 mL/second), and higher wall shear stress (WSS) along the posterior perforation margin (1.39 ± 0.52 vs 1.15 ± 0.58 Pa). The posterior WSS significantly correlated with crossover flow velocity (r = 0.77, p = 0.009) and was reduced by almost 67% postseptectomy, and by 29% postrepair. CONCLUSION: This is the first CFD analysis on an NSP patient cohort. NSP resulted in flow disturbance and increased WSS that potentially led to symptomatology. The removal of high stress points along the posterior margin may explain why posterior septectomy can be an effective treatment option. Aerodynamic abnormalities, in addition to perforation size and location, could serve as basis for future treatment decisions.

Computational fluid dynamics and trigeminal sensory examinations of empty nose syndrome patients.

OBJECTIVE: The precise pathogenesis of empty nose syndrome (ENS) remains unclear. Various factors such as nasal aerodynamics and sensorineural dysfunction have been suspected, although evidence is limited. This study reported the first examination of both nasal aerodynamics and trigeminal sensory factors in actual ENS patients. STUDY DESIGN: Prospective case control. METHODS: We enrolled six patients diagnosed with ENS. Three patients had pre- and post-inferior turbinate (IT) reduction computed tomography scans, which allowed comparison of their nasal aerodynamics changes through computational fluid dynamic (CFD) simulation. Their symptoms were confirmed through Sino-nasal Outcome Test-22, ENS 6-item Questionnaire, acoustic rhinometry, and rhinomanometry findings. Nasal trigeminal sensitivity that potentially mediates their perception of airflow was assessed via menthol lateralization detection thresholds (LDT) and compared with 14 healthy controls. RESULTS: Post-surgical reductions in nasal resistance were observed and significantly lower than normal (P < 0.05). Computational fluid dynamic analysis showed that, paradoxically for all ENS patients, IT reduction did not draw more airflow to the airway surrounding the ITs, but rather resulted in nasal airflow forming into a narrow jet toward the middle meatus region, leaving the airway surrounding the IT with significantly reduced airflow intensity and air-mucosal interactions (inferior region flow percentage reduced from 35.7% ± 15.9% to post-surgery 17.7% ± 15.7%, P < 0.05; inferior wall-shear-stress reduced from 7.5 ± 4.2 × 10-2 Pa to 3.4 ± 3.1 × 10-2 Pa, P < 0.01). Empty nose syndrome patients also had significantly impaired menthol LDT compared to healthy controls (P < 0.005). CONCLUSION: The results indicated that a combinatory of factors, including paradoxically distorted nasal aerodynamic, impaired sensorineural sensitivity, and potential predisposing conditions, may contribute to the development of ENS. LEVEL OF EVIDENCE: 3b. Laryngoscope, 127:E176-E184, 2017.

Principles of Pituitary Surgery.

Since the description of a transnasal approach for treatment of pituitary tumors, transsphenoidal surgery has undergone continuous development. Hirsch developed a lateral endonasal approach before simplifying it to a transseptal approach. Cushing approached pituitary tumors using a transsphenoidal approach but transitioned to the transcranial route. Transsphenoidal surgery was not "rediscovered" until Hardy introduced the surgical microscope. An endoscopic transsphenoidal approach for pituitary tumors has been reported and further advanced. We describe the principles of pituitary surgery including the key elements of surgical decision making and discuss the technical nuances distinguishing the endoscopic from the microscopic approach.

Single-blind randomized controlled trial of surfactant vs hypertonic saline irrigation following endoscopic endonasal surgery.

BACKGROUND: Recent discussion has revolved around formulations of irrigation in the postoperative functional endoscopic sinus surgery patient, specifically the efficacy of emulsion based nasal irrigations. METHODS: Forty adult candidates for endoscopic endonasal surgery with chronic rhinosinusitis (CRS) were prospectively randomized. The 22-item Sino-Nasal Outcome Test (SNOT-22) and 31-item Rhinosinusitis Outcome Measure (RSOM-31) quality of life assessments, as well as a phenyl ethyl alcohol (PEA) smell threshold test were obtained preoperatively and over 3 postoperative visits in a 4-month period. Repeated measures analyses and Fisher's exact tests were used to assess statistical differences. RESULTS: Of the 40 patients enrolled, 33, 32, and 26 patients were seen at postoperative visits 1, 2, and 3, respectively. The surfactant (S) and hypertonic saline (HS) irrigation groups both showed significant decreases in scores for both the SNOT-22 and RSOM-31 over time (both p < 0.0001), but no difference was seen between the 2 groups (p = 0.09, p = 0.5). PEA thresholds showed overall improvement in both groups 3 to 4 months after surgery: 62% (8/13) of HS patients and 50% (6/12) of S patients, but did not differ between the groups (p = 0.3). The S group reported significantly more side effects (52% vs 6%, p = 0.002) and had more patients stop the solution (20% vs 0%) and fewer S patients finished the study compared to the HS group. CONCLUSION: There were no significant differences in overall subjective symptoms related to sinonasal disease between S and HS irrigation, but tolerability appeared to be an issue. More patients reported side effects with S irrigation, and 20% receiving S irrigation stopped the solution, compared to none receiving HS irrigation.