Hemodynamic Changes Associated with Transcervical Laryngeal Injection of Botulinum Toxin

Abstract

Summary: Purpose:

Laryngeal dystonia is a chronic neurologic disorder characterized by intention-induced spasms of the vocal folds driven by aberrant central motor processing. The use of in-office transcervical botulinum toxin injection for the treatment of laryngeal disorders, such as laryngeal dystonia, has been deemed safe and efficacious. There is, however, no available data outlining the hemodynamic changes experienced by patients undergoing this frequently performed procedure.

Methods:

One hundred and one patients diagnosed with laryngeal dystonia were enrolled in this prospective study. These patients underwent transcervical laryngeal botulinum toxin injection to address their dysphonia. Vital signs where acquired prior to, and at the time of injection. Alterations in these parameters were then evaluated for statistical significance.

Results:

Statistically significant increases in mean heart rate (5.8 ± 10.8 bpm, p <0.0001), systolic and diastolic blood pressure (7.0 ± 9.5mmHg, p <0.0001; 8.7 ± 14.7 mmHg, p < 0.0001) were discovered. No statistically significant difference in oxygen saturation was noted and no patients in the study faced major adverse outcomes.

Conclusion:

Though these findings may not have related to clinically significant complication, our study demonstrates the importance of understanding potential stressors in a procedure routinely performed by laryngologists. This may result in more careful patient selection, alterations in procedure, and improved safety by acting in a timely fashion if alarming changes in hemodynamic parameters are noted.

1.1. Introduction

Laryngeal botulinum toxin (BTX) injection is a well-tolerated procedure which has been commonly performed in the office setting by laryngologists since the late 1980’s [1]. Patient safety, satisfaction and tolerance of many in-office laryngological procedures (IOLP) has been repeatedly demonstrated [2,3]. Despite study of the hemodynamic changes associated with such interventions, alterations in vital signs in patients undergoing transcervical laryngeal BTX injections has not been evaluated [2–4]. We sought to investigate the hemodynamic changes associated with the transcervical treatment of laryngeal dystonia using electromyography (EMG) guided laryngeal BTX injection.

Given the wide array of treatments and assessment provided through flexible endoscopes (biopsy, laser, and injection), particular attention has been provided to this modality. Procedures such as transnasal esophagoscopy (TNE) and flexible laryngeal surgery utilizing laser have been deemed safe and effective with minimal adverse effects based on studies performed by Postma et al., and Koufman et al., respectively [4,5]. When retrospectively reviewing hemodynamics during in-office endoscopic laryngeal procedures, Yung et al., and Morrison et al. independently noted statistically significant increases in vital signs including heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP), and oxygen (O2) saturation [2,3]. Due to these known changes Madden et al created an in-office pre-screening protocol to evaluate patient hemodynamic status prior to IOLP [6].

Despite statistically significant changes noted in HR, DBP, SBP and O2 saturation during flexible IOLP, no current literature exists exploring the hemodynamic changes that occur during in-office transcervical laryngeal BTX injection for the treatment of laryngeal dystonia. Though a rare clinical entity with a prevalence of 1 per 100,000, spasmodic dysphonia (SD) is not infrequently encountered when assessing patients with voice complaints. Given BTX injection has been long established as a safe and effective treatment of focal dystonia like SD, EMG-guided transcervical approaches to injection are frequently performed in clinic [7–10]. Despite the procedures reported safety, and establishment as the gold-standard in treatment of laryngeal dystonia, a paucity of literature exists regarding changes in hemodynamics experienced by patients during this intervention. The aims of this study were to assess vital sign parameters prior to and during BTX injection, and compare these data to established benchmarks for patient safety.

1.2. Material and methods

One hundred and one patients with spasmodic dysphonia undergoing transcervical laryngeal BTX injection were prospectively enrolled at Wake Forest Baptist Medical Center. Patients with tremor, mixed spasmodic dysphonia, and spasmodic dysphonia with tremor were not included in the study. Patient diagnoses were made by both fellowship trained laryngologists and speech language pathologists using perceptual and acoustic aerodynamic voice lab measures in addition to indirect laryngeal evaluation with phonatory tasks. Pre-procedural vital signs were obtained and rechecked at the time of injection. Vital signs were acquired using the Phillips SureSigns VS3 Monitor. The study parameters included systolic (SBP) and diastolic blood pressure (DBP), heart rate (HR), and oxygen (O2) saturation. Alterations in vital signs were then evaluated for statistical significance. Comparisons were made using median and paired t-test for heart rate, blood pressure, and oxygen saturation for pre-procedural and procedural measurements. Variations in outcome measures were then associated with sex, disease type, and presence of cardiovascular comorbidity. Participants taking antihypertensive or ionotropic medications were not asked to discontinue these medications in an effort to capture vital sign variance from their physiological baseline.

Data including age, sex, number of prior injections, type of spasmodic dysphonia (adductor SD versus abductor SD), and the presence or absence of cardiovascular comorbidities was also collected as noted in Table 1. Cardiovascular comorbidities including hyperlipidemia, atrial fibrillation, prior myocardial infarction, coronary artery disease, and arrhythmia were also noted. Individuals who had undergone multiple injections were included as a single participant in our study.

Table 1:

Patient Demographics

	No. (%)
Gender  Male  Female	88 (87) 13 (13)
Age (years)  30–49  50–69  >69	5 (5) 55 (54) 41(41)
Cardiovascular comorbidity  None  Present	60 (59) 41 (41)
Diagnosis  ADSD  ABSD	99 (98) 2 (2)
Prior injections  None  1–10  11–20  21–30  31–40  41–50  >50	11 (11) 34 (34) 20 (20) 12 (12) 5 (5) 5 (5) 14 (14)

Adductor spasmodic dysphonia: ADSD; Abductor spasmodic dysphonia: ABSD

A heart rate exceeding 100 bpm was considered tachycardic and severe hypertension was defined by a SBP greater than 180 mmHg or DBP greater than 110 mm Hg [2].

1.3. Results

In the group of one hundred and one subjects, eighty-eight were female (87%) and 13 were male (13%) with ages ranging from 33 to 87 years old (mean 67). Mean age by gender groups was 68 for females, and 62 for males. Presenting diagnoses included adductor spasmodic dysphonia (ADSD; n=99) and abductor spasmodic dysphonia ABSD; n=2).

Statistically significant increases in mean HR (5.8 ± 10.8 bpm, p <0.0001), SBP (7.0 ± 9.5mmHg, p <0.0001), and DBP (8.7 ± 14.7 mmHg, p < 0.0001) were noted. There was no statistically significant difference in O2 saturation. During the procedure one patient noted lightheadedness and another experienced self-resolving laryngospasm. No patients in the study faced any major adverse outcomes including cardiovascular events during the procedure.

Forty-one subjects (41%) had a preexisting cardiovascular comorbidity, such as hyperlipidemia, atrial fibrillation and heart disease. The presence of cardiovascular comorbidity was not statistically correlated with pre-procedure or procedural vital signs, nor significant change in measurements of HR, SBP, DBP or O2 saturation. Comparing variance in pre-procedure and procedural measurements of HR, SBP, DBP and O2 saturation between females (87%) and males (13%) did not reveal any significant differences. Additionally, when comparing patients with ADSD (98%) to those with ABSD (2%), no significant alterations in pre-procedure and procedural measurements of HR, SBP, DBP and O2 saturation were discovered.

1.4. Discussion

The popularity of all office-based laryngeal procedures has increased as surgeons and interventionalists continue to embrace such practices. Given the demonstrated safety and efficacy of these interventions, governing bodies including the American Academy of Otolaryngology recommend in-office treatments like BTX injections in the treatment of spasmodic dysphonia [11]. Despite the evidence of feasibility, efficacy, and patient satisfaction with office based transcervical laryngeal BTX injection in treating spasmodic dysphonia, a review of hemodynamic changes during this procedure has yet to be performed [9,12–15].

Our data is congruent with the accepted view that laryngeal botulinum injection is relatively safe as no one in the studied population experienced adverse safety events peri-procedurally. In our group of one hundred and one patients, only one experienced self-resolving laryngospasm and one other reported lightheadedness. There were no adverse cardiovascular (CV) events in any of the participating individuals. Several studies have revealed statistically significant increases in vital signs during office-based flexible endoscopic procedures of the aerodigestive tract [2,3]. Similar findings were noted in our studied population with laryngeal dystonia undergoing transcervical BTX injection. When comparing preprocedural vital signs to those at the time of injection, statistically significant increases in HR, SBP, and DBP were discovered independent of sex, diagnosis, or presence of preexisting CV comorbidity. Though the clinical significance of these alterations in vital signs are unknown, acute changes in hemodynamics can result in injury or complication before symptoms are encountered. Reports exist of patients sustaining neurological deficits, intracranial hemorrhage and cardiac dysfunction as a result of transient tachycardia and hypertension [2]. Fortunately, these uncommon complications are unlikely to result from small alterations in vital signs. Bradycardia, apnea, peripheral vasoconstriction, and blood flow redistribution have also been described as a result of laryngocardiac reflex stimulation [16]. In light of the hemodynamic changes associated with laryngeal interventions, appreciating the cumulative effects that could occur with stress of a transcervical procedure and activation of this reflex could prove beneficial. Lastly, baseline tachycardia and severe hypertension were noted in three and two patients, respectively. Though poorly controlled preexisting cardiovascular disease must be considered in the pre-procedural setting, vital sign variability and white coat hypertension (WCH) could explain such elevations in blood pressure and heart rate. SBP and DBP between visits can vary as greatly as 5–12 mmHg and 6–8 mmHg, respectively [17]. Additionally, the prevalence of WCH may be as high as 39%. Recent study has raised concern for the possibility of long-term cardiovascular risk in patients with WCH, but due to the diverse risk profile in this population, causation has not been established [18]. In review of our data, eight patients became tachycardic and six developed severe hypertension throughout the procedure. Of the hypertensive patients, four of the six had preexisting CV disease; a population in which acute changes in hemodynamics could prove problematic. Despite no significant correlation between CV disease and elevated pre-procedural vitals or change in procedural hemodynamics, there appeared to be a trend in acute blood pressure variance in this subgroup.

Limitations in this study include collection of two manual vital sign measures (before the procedure and at the time of injection) resulting in a limited data set. Naunheim et al. identified two major points during flexible transnasal procedures in which hemodynamic variables change significantly – the preparatory and laryngeal intervention phases [19]. Given the second set of vital signs in our study were acquired during injection, the laryngeal intervention, this measure likely captured a critical period in vital sign variance. This is further supported by significant changes discovered in HR, SBP and DBP which is congruent with the aforementioned article. Nevertheless, increasing the number of vital sign measures could improve the strength of the dataset. The absence of a defined control group is another limitation in our study. Though patients had pre-procedural vital signs taken and compared to their interventional hemodynamic parameters, a control group of age matched individuals not undergoing an office-based procedure in clinic could reveal additional insight. Our study also included a participant group with a wide range of prior injections. Though patients were included a single time, it is possible that as the number of experienced procedures increases, an individual’s comfort level with such an intervention could increase as well. Whether or not this change in tolerance also effects change in hemodynamics is unknown. Additionally, clinical and procedural environments have been demonstrated to effect anxiety. Therefore, this is another variable which could result in hemodynamic changes. Music and the use of aromatherapy, for example, have been postulated to evoke a sense of calm in high intensity situations [20]. Though the results of this study are translatable and valuable to all individuals performing transcervical laryngeal BTX injections, the effects may differ with unknown significant as environmental factors are altered.

1.5. Conclusions

This prospective study reveals statistically significant increases in HR, SBP and DBP during office-based transcervical laryngeal BTX injection in the treatment of spasmodic dysphonia. No statistically significant changes in oxygen saturations were noted and no patient suffered adverse events again verifying the overall safety of this procedure. Though the clinical significance of these findings remains unknown, otolaryngologists must appreciate the need for hemodynamic monitoring and identify at-risks patients such as those with baseline elevated blood pressure. Lastly, the results of this study may serve as control data for future investigation in office-based transcervical approaches to the larynx.

Table 2:

Pre-procedural and procedural vital sign measures

	Pre-procedural	Procedural	Difference	P-value
HR (mean, SD)	72.6 (12.2)	78.4 (16.5)	5.8 (10.8)	<0.0001
SBP (mean, SD)	139.2 (17.1)	146.2 (19.4)	7.0 (9.5)	<0.0001
DBP (mean, SD)	69.8 (14.2)	78.5 (16.2)	8.7 (14.7)	<0.0001
O2 sat (%, SD)	98.6 (1.8)	98.8 (1.9)	1.4 (1.9)	0.524

Heart rate: HR; Systolic blood pressure: SBP; Diastolic blood pressure: DBP; Oxygen saturations: O2 sat; Standard deviation: SD