Abstract
Background
Patients with unilateral vocal fold paralysis (UVFP) usually present with dysphonia, but can also be breathless and have problems with their swallowing. Speech and language therapy forms the initial mainstay of management in cases of UVFP, since up to 60% of cases will resolve spontaneously. If vocal fold paralysis persists surgery, in the form of injection medialisation, has been shown to be an effective intervention. What is currently unclear is which is the most effective material available for injection.
Objectives
To assess the effectiveness of alternative injection materials in the treatment of UVFP.
Search methods
We searched the Cochrane Ear, Nose and Throat Disorders Group Trials Register; the Cochrane Central Register of Controlled Trials (CENTRAL); PubMed; EMBASE; CINAHL; Web of Science; BIOSIS Previews; Cambridge Scientific Abstracts; ICTRP and additional sources for published and unpublished trials. The date of the most recent search was 23 March 2012.
Selection criteria
Randomised controlled trials (RCTs) of injectable materials in patients with UVFP. The outcomes of interest were patient and clinician‐reported improvement, and adverse events.
Data collection and analysis
Two authors independently selected studies from the search results and extracted data. We used the Cochrane 'Risk of bias' tool to assess study quality.
Main results
We identified no RCTs which met the inclusion criteria for this review. We excluded 18 studies on methodological grounds: 16 non‐randomised studies; one RCT due to inadequate randomisation and inclusion of non‐UVFP patients; and one RCT which compared two different particle sizes of the same injectable material.
Authors' conclusions
There is currently insufficient high‐quality evidence for, or against, specific injectable materials for patients with UVFP. Future RCTs should aim to provide a direct comparison of the alternative materials currently available for injection medialisation.
Keywords: Humans, Biocompatible Materials, Biocompatible Materials/administration & dosage, Injections, Injections/methods, Vocal Cord Paralysis, Vocal Cord Paralysis/pathology, Vocal Cord Paralysis/therapy, Vocal Cords, Vocal Cords/pathology
Plain language summary
Alternative materials injected into the vocal fold (cord) for unilateral vocal fold paralysis
Paralysis of one of the vocal folds (vocal cords) can have a significant impact upon a patient's quality of life. The affected patient may suffer with poor voice, breathlessness and problems with their swallowing. The treatment options include voice therapy, injection to the vocal cord or open surgery. The injection of a material into the affected vocal fold aims to improve voice, breathlessness and prevent episodes of aspiration (choking). There are a wide variety of injectable materials available and this review aimed to assess their effectiveness.
Our systematic review of the relevant literature could not identify any randomised controlled trials of sufficient quality to include in this review. There is currently insufficient high‐quality evidence to support the effectiveness of any particular injectable material. Further, well‐designed, robust research is required in this area.
Background
Description of the condition
The larynx has an important role communication, breathing and swallowing. Loss of function through unilateral vocal fold paralysis (UVFP) can therefore have a significant impact upon a patient's quality of life. Those affected by UVFP most commonly complain of a weak, breathy, rough voice and sometimes describe symptoms of breathlessness.
UVFP can be caused by a lesion affecting the vagus nerve at any point through its course on the affected side. Paralysis can thus be caused by dysfunction in the nucleus ambiguus, the vagus nerve or its recurrent laryngeal branch. The symptomatic effect upon voice depends on the site of the lesion. High lesions above the pharyngeal branch of the vagus nerve result in a nasal voice and greater sensory impairment (thus more episodes of aspiration), whereas lesions below this level, including lesions to the recurrent laryngeal nerve, result in a weak and breathy voice. Vocal fold paralysis that is suspected from history and examination is confirmed with direct visualisation of the larynx. An abnormality is regarded as a sign of underlying disease.
The aetiology of UVFP appears to have changed over the last few decades. A review of 280 consecutive patients with UVFP conducted in 1998 revealed increasing numbers of UVFP caused by extra‐laryngeal malignancies (24.7%) and surgical trauma (23.9%). Idiopathic causes, neurosurgical trauma, intubation and other neurological conditions are amongst the other causative factors (Benninger 1998).
UVFP is initially managed conservatively and the patient may be referred for speech therapy since up to 60% of idiopathic cases will spontaneously resolve within a year of presentation (Arviso 2010; Chen 2011; Sulica 2008; Tucker 1983). Improvement in a patient's symptoms can be due to a return in vocal fold motion or secondary to compensation from the contralateral normal‐functioning vocal fold. If the cause is known and the patient has a limited life‐expectancy surgical intervention can be considered earlier. Other indications for early intervention include clinical aspiration and patient intolerance of a period of voice change.
Speech therapy for UVFP involves patient education and training regarding vocal hygiene, phonation, optimisation of breathing and development of laryngeal musculature strength. Injection medialisation (discussed below) or external thyroplasty (laryngeal framework surgery) are used if surgical intervention is deemed necessary. External thyroplasty is performed using a Silastic or Gore‐Tex graft placed in a surgically fashioned window in the thyroid cartilage. This medialises the affected vocal fold, resulting in closer apposition of the vocal folds during phonation. External thyroplasty is usually performed under local anaesthesia, allowing the quality of the patient's voice to be assessed as the procedure is undertaken, and allows for optimal placement of the implant material. Reinnervation techniques, such as anastomosing the ansa cervicalis to the recurrent laryngeal nerve have also been used with varying degrees of success (Aynehchi 2010; Marina 2011).
Description of the intervention
One of the most commonly used methods for the management of UVFP is injection medialisation (transoral or transcutaneous) in which a material is injected into the space immediately lateral to the vocal fold using a needle. The aim is to either permanently or temporarily (depending upon the material used) add bulk to the atrophied vocal fold and to medialise the vocal fold to the midline. The rationale for this is to allow the contralateral, functioning vocal fold to meet the paralysed fold in or near the midline. Since Wilhelm Brunings first described the injection of paraffin paste, a variety of alternative materials have been tried. Despite this, the search for the ideal injectable material continues. The ideal injectable material would be biocompatible with host tissues, inert, non‐carcinogenic, easy to administer and not migrate or change in size over time (Shiotani 2009). Practically, it is also important that the material being used can be easily prepared and delivered to the intended location.
How the intervention might work
Injectable materials effectively treat UVFP by closing glottic gaps, which are usually small. This allows apposition to the unaffected vocal fold and therefore improved phonation and protection of the lower airway (Kumar 2006). In patients with large glottic gaps external thyroplasty or arytenoid adduction may be more appropriate. Injection laryngoplasty, however, is the least invasive method of improving glottic closure (Cantarella 2005).
Vocal fold injection medialisation can be performed under local or general anaesthesia. Local anaesthesia has the advantage of patient convenience and allows intra‐operative voice feedback to assess the amount of injected material required. General anaesthesia allows greater injection accuracy and improved patient comfort. There is, however, no voice feedback during the procedure to guide the intervention. The selected material can be injected either by the trans‐oral or trans‐cutaneous route.
The injected material should be placed on the medial surface of the vocalis muscle and the mid‐membranous and posterior vocal fold to prevent damage to the lamina propria. If material is injected too superficially (into Reinke's space) the voice can be permanently damaged. If there is over‐injection of material under general anaesthesia, airway compromise may occur and will only be apparent when the patient is extubated.
Before the introduction of modern techniques and the surge in the variety of materials available for injection, Teflon® was the only viable option for UVFP. Early surgical intervention with Teflon® was often unsatisfactory as the procedure is irreversible and can lead to granuloma formation through a foreign body reaction. Studies have revealed significant vocal deficits related to Teflon® injection which persist despite corrective procedures (Varvares 1995). Other permanent and long‐lasting materials which have been used include polyacrylamide gel and Vox® (polydimethylsiloxane gel; formerly known as Bioplastique®). These have both been shown to give good long‐term voice outcomes (Bergamini 2010; Lee 2007).
UVFP can now be treated more successfully with the injection of temporary materials. The effect is expected to last for weeks or months to allow time for spontaneous return of vocal fold function. The effect is temporary as the material injected is resorbed. The rate of resorption can be variable (e.g. fat) or quite predictable (in the case of Gelfoam®). The general characteristics of the new injectable materials available are important to consider when undertaking injection medialisation (discussed below). The materials currently in common use are Gelfoam®, collagen, fat, calcium hydroxylapatite and calcium phosphate, and hyaluronic acid.
Gelfoam® is rarely used as it has a relatively short length of action (four to six weeks) (Schramm 1978). Collagen, usually bovine, is a much more acceptable injectable material as it lasts for up to six months. It does require allergy testing, however, which takes up to four weeks to perform (Ford 1986).
Autologous fat is a highly unpredictable injectable substance with evidence of complete resorption within two months in some cases but persistence of the fat for years in others (Brandenburg 1996). Its major advantage is its good voice results despite less than perfect injection. Fat injection does demand over‐injection of 30% to 50% of material to allow for resorption. Multiple studies have shown that autologous fat injection for UVFP demonstrates good results in terms of phonation, which are comparable to those seen with external thyroplasty (Hartl 2009). The drawback of using fat is the unpredictable resorption rates which could necessitate re‐injection.
More recently utilised injectable materials include calcium hydroxylapatite and calcium phosphate. These are increasingly being used and studies involving these materials have shown good long‐term voice results as the material can last for up to two years (Chhetri 2004; Rosen 2004; Shiotani 2009).
Why it is important to do this review
The variety of materials available for injection laryngoplasty is testament to the fact that the ideal material has yet to be found. A systematic review of the available materials has not been conducted as yet. This review aims to provide valuable information regarding the best materials for injection laryngoplasty.
Objectives
To assess the effectiveness of different injection materials in the treatment of UVFP.
Methods
Criteria for considering studies for this review
Types of studies
Randomised controlled trials.
Types of participants
All patients with UVFP. We placed no restriction on age or gender.
Types of interventions
Trans‐oral and/or trans‐cutaneous injection for vocal fold medialisation, under general and/or local anaesthesia, directly comparing the currently available materials to one another. The materials directly being compared included, but were not confined to, polyacrylamide gel, Vox® (polydimethylsiloxane), Gelfoam®, collagen, autologous fat, calcium hydroxylapatite and calcium phosphate, and hyaluronic acid.
Types of outcome measures
Primary outcomes
Proportion of patients with improved voice.
Secondary outcomes
Voice improvement, as measured objectively by:
patient‐rated voice improvement (e.g. Voice Handicap Index (VHI), Voice Handicap Index‐10 (VHI‐10) and Voice‐Related Quality of Life (V‐RQOL));
clinician‐rated voice improvement (e.g. Grade, Roughness, Breathiness, Asthenia, Strain Scale (GBRAS), videostroboscopic measurements and maximum phonation time).
Patient and clinician‐reported adverse events, including episodes of aspiration, airway obstruction, foreign body reaction and extrusion.
Search methods for identification of studies
We conducted systematic searches for randomised controlled trials. No language, publication year or publication status restrictions were placed on our searches. We contacted original authors for clarification and for further data from unclear trial reports, and we arranged translations of papers where necessary. The date of the most recent search was 23 March 2012.
Electronic searches
We identified published, unpublished and ongoing studies by searching the following databases from their inception: the Cochrane Ear, Nose and Throat Disorders Group Trials Register; the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library 2012, Issue 1); PubMed; EMBASE; CINAHL; LILACS; KoreaMed; IndMed; PakMediNet; CAB Abstracts; Web of Science; BIOSIS Previews; ISRCTN; ClinicalTrials.gov; ICTRP; Google Scholar and Google.
We modelled subject strategies for databases on the search strategy designed for CENTRAL (see Appendix 1). Where appropriate, we combined subject strategies with adaptations of the highly sensitive search strategy designed by the Cochrane Collaboration for identifying randomised controlled trials and controlled clinical trials (as described in the Cochrane Handbook for Systematic Reviews of Interventions Version 5.0.2, Box 6.4.b. (Handbook 2011)).
Searching other resources
We scanned the reference lists of identified publications for additional trials and contacted trial authors where necessary. In addition, we searched PubMed, TRIPdatabase, The Cochrane Library and Google to retrieve existing systematic reviews relevant to this systematic review, and we scanned their reference lists for additional trials. We scanned the UK guidance on Collagen Injection for Vocal Cord Augmentation (NICE 2005) for additional trials, and we searched for conference abstracts using the Cochrane Ear, Nose and Throat Disorders Group Trials Register.
Data collection and analysis
Selection of studies
Two authors (RL and JMF) independently screened the results of the search to identify studies which broadly met the inclusion criteria. We reviewed those studies selected in full text and applied the inclusion criteria independently. Any conflict was resolved by referral to a third author (DC or NB).
Data extraction and management
At least two people (RL and JMF) independently performed assessment of the eligibility of studies and extracted data from study reports. We designed data collection forms carefully to target the objectives of the review. We piloted the form initially and refined it accordingly.
We planned to address multiple reports of the same study by extracting data from each report separately and combining the information across multiple data collection forms.
Disagreements were dealt with by discussion among the authors RL and JMF initially and where necessary referral to an arbitrator (DC or NB) if required. Although not required, we planned to address any disagreements that could not be resolved by contacting the study authors; if this was unsuccessful, we planned to report the disagreement in the review.
Assessment of risk of bias in included studies
Had studies suitable for inclusion been identified, RL and JMF would have independently undertaken assessment of the risk of bias of the included trials with the following taken into consideration, as guided by the Cochrane Handbook for Systematic Reviews of Interventions (Handbook 2011):
sequence generation;
allocation concealment;
blinding;
incomplete outcome data;
selective outcome reporting; and
other sources of bias.
We planned to use the Cochrane 'Risk of bias' tool in RevMan 5.1 (RevMan 2011), which involves describing each of these domains as reported in the trial and then assigning a judgement about the adequacy of each entry (low risk of bias, high risk of bias or unclear risk of bias).
Measures of treatment effect
For dichotomous data, we planned to calculate individual and pooled statistics as risk ratio (RR) with 95% confidence intervals (CI).
We planned to analyse continuous data using mean differences (MD) and standardised mean differences (SMD) with 95% CIs.
Unit of analysis issues
We intended to take into account the level at which randomisation occurred. We would have made an assessment of the randomisation into simple parallel groups and of the variations of this such as cluster‐randomised trials, cross‐over trials or multiple observations for the same outcome.
Dealing with missing data
Where possible we planned to contact the original investigators of the study to obtain the missing data. We would have made the methods used to allow for the missing data explicit. We would have addressed the potential impact of missing data on the findings of the review in the assessment of risk of bias and in the Discussion section of the review.
Assessment of heterogeneity
We planned to assess heterogeneity by inspecting the overlap of confidence intervals for the results of individual studies. Horizontal lines depicting these graphically were to be utilised. We planned to conduct formal assessment of heterogeneity using the Chi2 test and the I2 statistic available in RevMan 5.1 (RevMan 2011).
Assessment of reporting biases
Where possible, we planned to conduct a sensitivity analysis of small study effects and use a funnel plot to assess for publication bias if the number of available studies was sufficient.
Data synthesis
We extracted data from included studies and entered data into RevMan 5.1 for statistical analysis. In the event of incomplete data we planned to contact the relevant authors to obtain further data. If appropriate, we planned to conduct a meta‐analysis. We sought statistical advice where necessary. If the data obtained were in the form of means and standard deviations, we planned to summarise the effects on outcomes as standardised mean differences (SMD) with 95% CIs and using an intention‐to‐treat analysis when performing all analyses. If possible, we intended to calculate pooled estimates using a fixed‐effect model. However, if there was substantial statistical heterogeneity (an I2 value > 50%, as specified in the Cochrane Handbook for Systematic Reviews of Interventions), or clinical heterogeneity, we were to use a random‐effects model (Handbook 2011). We would have considered a sensitivity analysis to compare fixed and random‐effects estimates.
Subgroup analysis and investigation of heterogeneity
No specific subgroup analysis was planned.
Sensitivity analysis
If the data obtained were suitable for meta‐analysis, we planned to carry out a sensitivity analysis and present the results in a summary table. This may not have been appropriate if the number of trials which met the inclusion criteria was low.
Results
Description of studies
Results of the search
Our searches in March 2012 identified a total of 230 references, which dropped to 143 after removal of duplicates and a broad subject sift was performed. From these we highlighted 18 as being potentially relevant. See Figure 1 for a flow chart depicting the search history.
1.
Study flow diagram.
Included studies
After full review of the relevant articles no studies met the inclusion criteria.
Excluded studies
We excluded 18 studies for the following reasons (see Characteristics of excluded studies).
Study type
Brandenburg 1996 prospectively reported the outcome of autologous fat injection (10 patients) in a non‐randomised manner.
Chang 1997 reported a cross‐sectional study of 21 patients with UVFP undergoing injection medialisation using Teflon®.
Cheng 2009 studied a combination of autologous fat and fascia lata utilising a retrospective analysis of case records in 12 patients.
Dworkin 2006 was not a randomised controlled trial. This study prospectively reported the outcomes of two groups of 10 patients. The first group underwent medialisation thyroplasty and the second group injection thyroplasty.
Fang 2009 is a cross‐sectional study of 33 patients that measured the outcome of fat injection using three‐dimensional imaging and voice‐related outcomes.
Ford 1986, a prospective study of 54 patients undergoing collagen injection (Zyderm®) for UVFP, was not randomised.
Harries 1998 was not a randomised study. It prospectively studied eight patients who had injection medialisation with Teflon® paste.
Hartl 2009 was a prospective comparative study of two groups; one undergoing medialisation thyroplasty (46 patients) and the other injection thyroplasty (48 patients) with autologous fat.
Lee 2007 was a cross‐sectional study of 34 patients undergoing polyacrylamide hydrogel injection laryngoplasty.
Mortensen 2009 was excluded as it is a retrospective review of three techniques for treating UVFP which included 45 patients undergoing injection laryngoplasty.
Reijonen 2009 reported retrospective outcomes in 43 patients who underwent injection laryngoplasty with autologous fascia between 1996 and 2003.
Rosen 2004 prospectively investigated a new injectable calcium hydroxylapatite‐based material in 11 terminally ill patients. Five patients were available for short‐term follow‐up (six months). This study was not a randomised controlled trial. Similarly, Rosen 2009 was not randomised but was conducted in a prospective manner. This study reported long‐term results (up to 12 months) of vocal fold augmentation with calcium hydroxylapatite injected under local anaesthesia in 63 patients with UVFP.
Shaw 1997 retrospectively reviewed the long‐term results (12 months) of injection with autologous fat in 22 patients.
Sittel 2006 prospectively evaluated the use of polydimethylsiloxane particles injected via the trans‐oral route under general anaesthesia in 14 patients. This study was not randomised and follow‐up was relatively short at 4.1 months (median).
Trial design
Hertegard 2002 and Hertegard 2004 are reports concerning the same group of patients. Both are randomised, controlled, single‐blinded trials comparing hylan B® and bovine collagen injection medialisation. This study enrolled 70 patients. Only 35 of the 70 patients had UVFP and the remaining 35 had either unilateral atrophy or bilateral bowing. Therefore patients with different diagnoses were included in the same patient group. Thus only the 35 patients with UVFP meet the inclusion criteria for this review. Unfortunately, the method of randomisation was described as being 'consecutive' which is not robust. Furthermore, after randomisation, 47 patients underwent hylan B® injection and 23 bovine collagen injection. With a 'consecutive' randomisation process one would have expected the groups to have been of equal (or near‐equal) size. In any case the paper appears to be comparing not only hylan B® injection with collagen injection but also, as previously discussed, patients with different diagnoses, UVFP and unilateral atrophy or bilateral bowing. The patients in this study were blinded to the injection material, however the surgeon was not, which represents a potential source of bias.
Lau 2010 compared two different particles sizes of the same injectable material, hyaluronic acid. This study was single‐blinded and was therefore open to bias.
Outcome measures
Brandenburg 1996 only utilised magnetic resonance imaging (MRI) evaluation of injected autogenous fat in 10 patients and therefore looked at outcome measures not being evaluated in this review.
Risk of bias in included studies
Our review of the literature found no studies which met the inclusion criteria.
Effects of interventions
No studies could be included in this current version of the review.
Discussion
The aims of treatment for UVFP are two‐fold: to improve voice and alleviate aspiration. A patient's desire to improve their voice quality may be the sole indication if there is no evidence of aspiration. Laryngeal nerve function can return to normal even if there is iatrogenic injury to the nerve, thus any surgical intervention should ideally be delayed for a year to allow for any spontaneous regeneration. As discussed earlier, the main treatment modalities for UVFP include speech and language therapy, injection medialisation and thyroplasty (laryngeal framework surgery). Voice therapy can be highly effective for treating voice deficits associated with UVFP. However, when this is ineffective, or treatment reaches a plateau, surgical intervention may be considered (Rubin 2007).
Injection medialisation has gained increasing popularity over the past few years. This procedure is appealing for many reasons including ease of administration, relative low cost and greater understanding and quality of the various materials available (King 2007; Kwon 2004). Various materials have been studied and this review aimed to assess them to evaluate their effectiveness in the treatment of UVFP.
Summary of main results
There were no studies that met the inclusion criteria in this review.
Overall completeness and applicability of evidence
Not applicable.
Quality of the evidence
A review of the literature returned a number of potentially relevant studies. The majority of these, however, were either prospective studies which were not randomised or were retrospective in design. The relevant studies that were randomised, prospective trials could not be included in this study due to methodological issues. For example the Hertegard 2002/Hertegard 2004 randomised controlled trial comparing hylan B® and collagen injection included patients with differing diagnoses (paresis, atrophy and bilateral bowing), was randomised in a non‐robust manner and was single‐blinded.
Potential biases in the review process
Not applicable.
Agreements and disagreements with other studies or reviews
Not applicable.
Authors' conclusions
Implications for practice.
There is no high‐quality evidence currently for or against specific injectable materials for patients with UVFP.
Implications for research.
Well‐designed randomised controlled trials with adequate (long‐term) follow‐up, which are adequately powered, are needed to assess the effectiveness of injectable materials for UVFP. Ideally, these trials would be multicentre, with a stringent protocol, comparing commonly used materials for injection medialisation. Patient selection will be an important consideration in the drawing up of inclusion criteria for future RCTs (e.g. would similar criteria be applied to patients with recurrent laryngeal nerve injuries of different aetiologies, such as idiopathic, iatrogenic and neoplastic injuries). Future studies should be reported according to the CONSORT statement to ensure that rigorous standards in completeness, clarity and transparency of RCT reporting are met (CONSORT 2010).
We recommend that voice outcomes should be reported using validated tools designed to measure both patient‐rated voice improvements (e.g. Voice Handicap Index (VHI), Voice Handicap Index‐10 (VHI‐10) and Voice‐Related Quality of Life (V‐RQOL)) and clinician‐rated voice improvements (e.g. Grade, Roughness, Breathiness, Asthenia, Strain Scale (GBRAS), videostroboscopic measurements and maximum phonation time). In addition any adverse events/outcomes with regards to the injectable material being tested should be reported.
Acknowledgements
We are grateful to Jenny Bellorini in the Cochrane Ear, Nose and Throat Disorders Group for her assistance and to Gemma Sandberg for help with the design and running of the search strategy. We also thank Marina Mat Baki for her help with the Background section.
Appendices
Appendix 1. Search strategies
| CENTRAL | PubMed | EMBASE (Ovid) |
| #1 MeSH descriptor Vocal Cord Paralysis explode all trees #2 UVCP OR ULNP #3 MeSH descriptor Vocal Cords explode all trees #4 (vocal:ti AND fold*:ti) OR (vocal:ti AND cord*:ti) OR (vocal:ti AND chord*:ti) OR laryngeal:ti #5 #3 OR #4 #6 MeSH descriptor Paralysis explode all trees #7 paralys*:ti OR palsy:ti OR palsies:ti OR paresis:ti #8 #6 OR #7 #9 #5 AND #8 #10 MeSH descriptor Glottis explode all trees #11 glotti*:ti #12 #10 OR #11 #13 insuffic*:ti OR incompeten*:ti #14 #12 AND #13 #15 #1 OR #2 OR #9 OR #14 #16 MeSH descriptor Injections explode all trees #17 MeSH descriptor Prosthesis and Implants explode all trees #18 inject* OR implant* #19 #16 OR #17 OR #18 #20 #15 AND #19 | #1 “Vocal Cord Paralysis” [MeSH] OR UVCP OR ULNP #2 “Vocal Cords” [MeSH] OR (vocal:ti AND fold*:ti) OR (vocal:ti AND cord*:ti) OR (vocal:ti AND chord*:ti) OR laryngeal:ti #3 “Paralysis” [MeSH] OR paralys*:ti OR palsy:ti OR palsies:ti OR paresis:ti #4 #2 AND #4 #5 (“Glottis” [MeSH] OR glotti*:ti) AND (insuffic*:ti OR incompeten*:ti) #6 #1 OR #4 OR #5 #7 “Injections” [MeSH] OR “Prosthesis and Implants” [MeSH] OR inject* OR implant* #8 #6 AND #7 | 1. *vocal cord paralysis/ 2. (uvcp or ulnp).tw. 3. vocal cord/ 4. ((vocal and fold*) or (vocal and cord*) or (vocal and chord*) or laryngeal).ti. 5. exp paralysis/ 6. (paralys* or palsy or palsies or paresis).ti. 7. 5 or 6 8. 3 or 4 9. 7 and 8 10. glottis/ 11. (nsuffic* or incompeten*).ti. 12. glotti*.ti. 13. 10 or 12 14. 11 and 13 15. 1 or 2 or 9 or 14 16. exp injection/ 17. exp implantation/ 18. (inject* or implant*).tw. 19. 16 or 17 or 18 20. 15 and 19 |
| Web of Science/BIOSIS Previews (Web of Knowledge) | CINAHL (EBSCO) | ICTRP |
| #1 TI=(uvcp OR ulnp OR ((vocal OR laryngeal) AND (paralys* OR pals* OR paresis*)) OR (glotti* AND (insuffic* OR imcompeten*))) #2 TS=(inject* OR implant*) #3 #2 AND #1 | S1 (MH "Vocal Cord Paralysis") S2 TX uvcp OR ulnp S3 (MH "Vocal Cords") S4 TI (vocal OR laryngeal) S5 (MH "Paralysis+") S6 TX paralys* OR pals* OR paresis* S7 S3 or S4 S8 S5 or S6 S9 S7 and S8 S10 (MH "Glottis") S11 TI glotti* S12 S10 or S11 S13 insuffic* OR imcompeten* S14 S12 and S13 S15 S1 or S2 or S9 or S14 | vocal AND inject* OR voice AND inject* OR glott* AND inject* OR laryn* AND inject* OR uvcp AND inject* OR ulnp AND inject* |
Characteristics of studies
Characteristics of excluded studies [ordered by study ID]
| Study | Reason for exclusion |
|---|---|
| Brandenburg 1996 | ALLOCATION:
Not a randomised controlled trial Outcome measures ‐ only utilised MRI evaluation of injected autogenous fat |
| Chang 1997 | ALLOCATION: Not a randomised controlled trial |
| Cheng 2009 | ALLOCATION: Not a randomised controlled trial |
| Dworkin 2006 | ALLOCATION: Not a randomised controlled trial |
| Fang 2009 | ALLOCATION: Not a randomised controlled trial |
| Ford 1986 | ALLOCATION: Not a randomised controlled trial |
| Harries 1998 | ALLOCATION: Not a randomised controlled trial |
| Hartl 2009 | ALLOCATION: Not a randomised controlled trial |
| Hertegard 2002 | ALLOCATION: Randomised controlled trial; 'consecutive' randomisation is not robust; single‐blinded study (the surgeon was not blinded) PARTICIPANTS 35/70 patients studied did not have UVFP, they had atrophy or bilateral bowing Reports the same patient group as Hertegard 2004 |
| Hertegard 2004 | ALLOCATION: Randomised controlled trial; 'consecutive' randomisation is not robust; single‐blinded study PARTICIPANTS 35/70 patients studied did not have UVFP, they had atrophy or bilateral bowing Reports the same patient group as Hertegard 2002 |
| Lau 2010 | ALLOCATION:
Prospective randomised controlled trial ‐ single‐blinded study, open to bias PARTICIPANTS: 41 patients over 18 years requiring medialisation for UVFP INTERVENTIONS: Compared 2 different particles sizes of the same injectable material, hyaluronic acid |
| Lee 2007 | ALLOCATION: Not a randomised controlled trial |
| Mortensen 2009 | ALLOCATION: Not a randomised controlled trial |
| Reijonen 2009 | ALLOCATION: Not a randomised controlled trial |
| Rosen 2004 | ALLOCATION: Not a randomised controlled trial |
| Rosen 2009 | ALLOCATION: Not a randomised controlled trial |
| Shaw 1997 | ALLOCATION:
Not a randomised controlled trial Included patients with atrophy of the vocal cord and not paresis |
| Sittel 2006 | ALLOCATION: Not a randomised controlled trial |
MRI: magnetic resonance imaging UVFP: unilateral vocal fold paralysis
Differences between protocol and review
Studies that compared injectable techniques under local and/or general anaesthesia, via the trans‐oral and/or trans‐cutaneous routes, were included in the review. This was done to increase the number of studies available for the review. In addition, we modified the primary outcome measure to become the 'Proportion of patients with improved voice' to reflect the results of this systematic review and the original primary outcome measures have now been included under secondary outcome measures.
Contributions of authors
Raj Lakhani: preparation of protocol, literature search, selecting studies and collecting data, analysing data and where relevant undertaking meta‐analysis, presenting and interpreting results, drawing conclusions, writing systematic review.
Jonathan M Fishman: preparation of protocol, literature search, selecting studies and collecting data, analysing data and where relevant undertaking meta‐analysis, presenting and interpreting results, drawing conclusions, writing and editing systematic review.
Declan Costello: preparation of protocol, presenting and interpreting results, drawing conclusions.
Nigel Bleach: preparation of protocol, presenting and interpreting results, drawing conclusions.
Martin Birchall: editing and approving the systematic review.
Sources of support
Internal sources
None, Not specified.
External sources
None, Not specified.
Declarations of interest
None known.
New
References
References to studies excluded from this review
Brandenburg 1996 {published data only}
- Brandenburg JH, Unger JM, Koschkee D. Vocal cord injection with autogenous fat: a long‐term magnetic resonance imaging evaluation. Laryngoscope 1996;106(2 Pt 1):174‐80. [DOI] [PubMed] [Google Scholar]
Chang 1997 {published data only}
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Cheng 2009 {published data only}
- Cheng Y, Li ZQ, Huang JZ, Xue F, Jiang MJ, Wu KM, et al. Combination of autologous fascia lata and fat injection into the vocal fold via the cricothyroid gap for unilateral vocal fold paralysis. Archives of Otolaryngology ‐‐ Head and Neck Surgery 2009;135(8):759‐63. [DOI] [PubMed] [Google Scholar]
Dworkin 2006 {published data only}
- Dworkin JP, Shah AG, Stachler RJ, Meleca RJ. Medialization thyroplasty versus injection laryngoplasty for unilateral vocal fold paralysis: a comparative analysis of functional outcomes. Journal of Medical Speech‐Language Pathology 2006;14(1):1‐12. [Google Scholar]
Fang 2009 {published data only}
- Fang TJ, Lee LA, Wang CJ, Li HY, Chiang HC. Intracordal fat assessment by 3‐dimensional imaging after autologous fat injection in patients with thyroidectomy‐induced unilateral vocal cord paralysis. Surgery 2009;146(1):82‐7. [DOI] [PubMed] [Google Scholar]
Ford 1986 {published data only}
- Ford CN, Bless DM. Clinical experience with injectable collagen for vocal fold augmentation. Laryngoscope 1986;96(8):863‐9. [DOI] [PubMed] [Google Scholar]
Harries 1998 {published data only}
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Hartl 2009 {published data only}
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