Frozen Cadaveric Rib Grafts in Primary or Revision Rhinoplasty: A Systematic Review and Meta-analysis

Abstract

Background:

Primary and secondary rhinoplasty frequently require cartilage grafts to support the osseocartilaginous framework. Autologous and irradiated homologous cartilage have been used as sources, each with pros and cons. Recently, fresh frozen cadaveric rib grafts have gained popularity, potentially reducing complications associated with autologous or homologous irradiated cartilage grafts. However, outcomes associated with these grafts have only been assessed in small studies. We conducted a meta-analysis to provide a comprehensive assessment of outcomes after primary and revision rhinoplasty using fresh frozen rib grafts.

Methods:

For this systematic review and meta-analysis, MEDLINE, Embase, Scopus, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov were searched for articles published up to January 2023. Hybrid graft patients were excluded to ensure homogeneity. Data were pooled using a random-effects model and analyzed using Open Meta Analyst. Effect sizes were calculated for complications, including warping, resorption, infection, and revision surgery.

Results:

Of 306 citations, 5 studies were included in the meta-analysis. Our study, involving 440 patients, concluded a low overall complication rate but revealed a higher rate in studies with longer follow-up (7.6%; 95% confidence interval: 3.4%–13.3%) and in cases involving both primary and revision rhinoplasty (12.7%; 95% confidence interval: 4.8%–23.6%).

Conclusions:

This meta-analysis suggests that frozen cadaveric costal cartilage may be used for rhinoplasty with low complication rates. However, longer follow-up reveals higher complication rates (7.6%), and cases involving both primary and revision rhinoplasty show a complication rate of (12.7%). These findings emphasize the need for extended postoperative monitoring and caution when interpreting long-term outcomes.

Takeaways

Question: What are the outcomes and complication rates of using fresh frozen rib grafts in primary and secondary rhinoplasty?

Findings: This meta-analysis, aggregating results from 5 studies with a total of 440 patients, showed low rates of complications when using fresh frozen rib grafts in rhinoplasty. These complications include infections (2.6%), warping (2.3%), revision surgery (4.4%), and resorption (1.8%).

Meaning: Fresh frozen rib grafts could be an advantageous choice for rhinoplasty due to comparable complication rates to other graft types, no donor site morbidity, and decreased resorption rates compared with irradiated homologous cartilage.

INTRODUCTION

Cosmetic and reconstructive rhinoplasty provides a significant challenge to rhinoplasty surgeons. Septal cartilage is the preferred source of graft, but it can prove to be insufficient. A substantial quantity of cartilage may be needed to provide strength, structural framework, and a patent upper airway specifically for dorsal augmentation.¹ Multiple sources of grafts can be used as an alternative. Grafts have the advantage of being versatile, allowing them to fulfill the different structural and functional requirements unique to each patient. The optimal cartilage graft would provide the necessary strength and cosmetic and structural function, along with minimizing the risk of complications, including infections, resorption, warping, and revision surgery.¹

Septal cartilage grafts have been the preferred source for rhinoplasties; however, autologous costal cartilage is preferred when a significant amount of cartilage is required and septal cartilage is not available. Autologous and homologous irradiated costal cartilage grafts are frequently used as a graft source. Harvesting costal cartilage has the added risk of donor site morbidity associated with obtaining the cartilage, including the risk of pneumothorax, postoperative pain, and hypertrophic scar, along with increased operative time.^2,3 Homologous irradiated costal cartilage grafts are exposed to high levels of radiation, usually more than 25 kGy, substantially increasing the resorption rate of the cartilage, frequently requiring revision surgery.⁴ These complications may be overcome by using fresh frozen cadaveric rib graft, a novel graft source that has been recently gaining popularity. They have the advantage of being readily available and have proven to be safe and efficacious, with a minimal rate of complications.

Fresh frozen cadaveric rib grafts may mitigate the risks associated with harvesting autologous cartilage and irradiating cartilage, and may have a lower complication rate.⁵ However, the outcomes associated with the use of fresh frozen cadaveric grafts have only been assessed in small clinical studies that have yielded varying results. Thus, we conducted a meta-analysis to provide a holistic, better-powered assessment of outcomes after primary and revision rhinoplasty using fresh frozen cadaveric grafts.

METHODS

For this systematic review and meta-analysis, the Preferred Reporting Items for Systematic Reviews and Meta-analyses reporting guidelines were followed.⁶ Using the population, intervention, comparator, outcome, and study design framework for this systematic review, the population of interest was patients older than 15 years of age undergoing revision or complex rhinoplasty using fresh frozen rib grafts. Single-arm studies were included, and the outcome of interest was complications arising due to the graft, namely warping, resorption, infections, need for revision, and total complications. The study design included all original study types excluding case reports.

Two independent researchers performed a literature review using the following search strategy: (septorhinoplasty OR rhinoplasty) AND (fresh frozen costal cartilage OR costal cartilage allograft OR rib graft OR cadaveric cartilage graft OR homologous costal cartilage graft) in MEDLINE, Embase, and Scopus, keeping the inclusion criteria in mind. No language restrictions were set. No filters were applied. Searches were performed for all articles starting from inception to January 2023, and a total of 306 results were found.

All the search results were exported to EndNote Reference Library software, and duplicates were removed. Articles were screened by 2 independent reviewers who initially screened the articles based on title and abstract followed by the full text. All discrepancies were discussed. Articles were included in our meta-analysis if they met the following criteria: (1) patients older than 15 years of age, (2) primary or revision rhinoplasty, (3) original observational studies, (4) randomized controlled trials, and (5) all frozen rib grafts (fresh frozen and lyophilized). Articles were excluded from our meta-analysis based on the following criteria: (1) irradiated homologous grafts, (2) use of hybrid grafts, (3) graft origin not specified, (4) studies involving the pediatric population, (5) nonhuman studies, (6) cadaveric studies, (7) Binder syndrome, (8) case reports, (9) autoimmune diseases, and (10) cleft rhinoplasty performed. This led to 5 articles that fulfilled the inclusion and exclusion criteria.^1,5,7–9

Study data and complications, including warping, resorption, infections, need for revision, and total complications, were extracted and recorded in a database, along with the required data for completing a modified version of the Cochrane Collaboration’s risk of bias tool. Domains specific to randomized control trials (sequence generation and allocation concealment) were marked as not applicable because none of the included studies were randomized clinical trials. Study characteristics, baseline demographics, outcome data, and safety data were extracted into a predesigned Excel spreadsheet. Data extraction and quality assessment were conducted independently by 2 reviewers, and discrepancies were resolved via discussion.

All statistical analyses were performed using Open Meta Analyst. The incidence of each complication was extracted and used to estimate the effect size. The primary meta-analysis was performed for the incidence of total complications (defined as the number of patients who experienced 1 or more complications), infections (any erythema requiring antibiotic therapy), warping (defined as postoperative change in cartilage shape), resorption (defined as loss of cartilage postoperatively due to infection or otherwise), and revision surgery (defined as any need of major surgery or minor procedure after initial surgery). Rates were calculated as patients experiencing the complication out of the total number of patients. Pooled effect sizes were calculated using random-effects models and were expressed as the risk with a 95% confidence interval (CI). A P-value less than 0.05 was considered significant. Heterogeneity was measured using I².

RESULTS

The search strategy resulted in 306 citations. After inclusion and exclusion criteria were applied, 5 studies qualified for meta-analysis,^1,5,7–9 all of which were retrospective cohort studies (Fig. 1). These studies comprised a total of 440 patients. The studies were published between 2007 and 2022, the majority of which were from 2019 onward; the mean sample size was 88 (range, 21–226 patients); and the studies were from 3 countries, United States (n = 3), Canada (n = 1), and South Africa (n = 1). The mean follow-up time was 10.9 months in the studies that reported it, although 1 study did not. The patient baseline characteristics of the studies are presented in Table 1.

Fig. 1.

Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) flow diagram for included studies.

Table 1.

Baseline Patient Demographics

Study (Year)	Patients, n	Mean Age, y	Sex M/F, %	Mean Follow-up Time, mo	Revision Rhinoplasties, n
Milkovich and Ahmad1 (2022)	21	39	19/81	15.0	11
Rohrich et al5 (2022)	226	40.6	18/82	12.2	226
Rogal et al8 (2021)	26	42	33/77	15.9	19
Mohan et al7 (2019)	50	40	24/76	3.4	50
Swanepoel and Fysh9 (2007)	117	—	—	—	—

Primary Analysis

No single complication was accounted for in all 5 of the pooled studies, and hence, we established total complications as the primary outcome. Our meta-analysis concluded a low rate of all complications with total complications (4.4%; 95% CI: 1.1%–9.8%), infections (2.6%; 95% CI: 1.2%–4.6%), resorption (1.8%; 95% CI: 0.2%–5.2%), warping (2.3%; 95% CI: 0.9%–4.3%), and revision surgery (4.4%; 95% CI: 1.0%–9.9%). The outcomes are summarized in Table 2, and forest plots for each outcome can be seen in Figure 2.

Table 2.

Overall Summary of Meta-analysis

Outcome	No. Studies	No. Patients	Pooled Event Rate, % (95% CI)	Heterogeneity, I2
Total complications	5	440	4.4 (1.1–9.8)	73.8
Infections	4	323	2.6 (1.2–4.6)	0
Resorption	4	214	1.8 (0.2–5.2)	40.2
Warping	3	297	2.3 (0.9–4.3)	0
Revision surgery	3	273	4.4 (1.0–9.9)	40.9

Fig. 2.

Complication rates in studies using frozen cadaveric rib grafts for rhinoplasty.

Subgroup Analysis

We conducted a subgroup analysis to address some of the heterogeneity. Total complication rates were compared between the 3 studies that reported longer follow-up^1,5,8 time with the 2 studies that reported shorter or no follow-up time.^7,9 The analysis (Fig. 3) showed a significantly higher total complication rate in the longer follow-up subgroup (7.6%; 95% CI: 3.4%–13.3%) compared with the subgroup with shorter or unreported follow-up (0.8%; 95% CI: 0.0%–2.7%). We also compared total complication rates between studies with exclusively revision rhinoplasty patients with studies that had both primary and revision rhinoplasty patients. The analysis (Fig. 4) showed a significantly higher rate of total complications in the primary and revision rhinoplasty subgroup (12.7%; 95% CI: 4.8%–23.6%) versus the exclusively revision rhinoplasty subgroup (4.4%; 95% CI: 1.1%–9.8%).

Fig. 3.

Subgroup analysis based on follow-up time.

Fig. 4.

Subgroup analysis of primary and revision rhinoplasty studies vs exclusively revision rhinoplasty studies.

It is important to note that although the overall complication rate was found to be low (4.4%), longer follow-up times (7.6%) and studies involving both primary and revision rhinoplasty (12.7%) presented significantly higher complication rates. These findings suggest that the duration of follow-up plays a crucial role in identifying complications, particularly in more complex rhinoplasty cases.

DISCUSSION

The purpose of this study was to identify the incidence of various complications involved in using frozen, aseptically processed, nonterminally sterilized costal grafts for primary and secondary rhinoplasty. The main methods of reconstruction of the nasal osseocartilaginous framework include alloplastic, autologous, homologous irradiated, and nonirradiated frozen grafts. Alloplastic grafts have the advantage of being readily available, being in an unlimited bulk, having no donor site morbidity, and being able to be carved according to the requirements of the case.¹⁰ However, they have high rates of infection and implant extrusion.¹⁰ Autologous grafts include grafts from the nasal septum, ear cartilage, or costal cartilage. When the requirements are low, septal or ear cartilage is preferred because they are versatile to use in both on-lay and structural grafts, within the same surgical field, and leave an inconspicuous scar.^11,12 Septal cartilage is the preferred source in non-Asian primary rhinoplasties because the quantity of septal cartilage is enough to address the aesthetic and functional needs of the patients. However, these grafts have limited utility due to their low quantity and intrinsic structural fragility.¹³

Costal cartilage autologous grafts have a rigid structure and can be used to provide the support needed, especially in secondary rhinoplasty when a greater quantity of cartilage is required.¹⁴ It can be carved precisely to minimize warping as well. Warping can be further minimized by using the central core of ribs and using ribs with a larger cross-sectional area. Moreover, older patients have stiff costal cartilages, which are less prone to warping. The significant donor site morbidity involved limits its use. One major complication is the pain associated with it, which can result in postoperative atelectasis and prolonged narcotic pain control, increasing the risk of dependence.¹⁵ Accidental opening of the pleural cavity (0.1%–2.1%) may result in traumatic pneumothorax.² Moreover, the incision technique used by the surgeon can result in a significant scar.³ All of these factors result in a greater intraoperative time and a higher cost of the procedure, which can be mitigated by using fresh frozen cadaveric grafts. Homologous irradiated grafts are not associated with increased intraoperative time or donor site morbidity. They are sterilized using high doses of gamma radiation usually more than 25 kGy resulting in a significantly higher resorption rate of 30% compared with 3% in autologous grafts, according to Wee et al.⁴ This high radiation induces the production of free radicals, which alters the histological properties of the cartilage by decreasing the collagen and proteoglycans content and reducing the size and uniformity of viable chondrocytes.^4,16

Nonirradiated, aseptically processed, frozen rib grafts are available off the shelf and are a safe, viable option for rhinoplasty. These grafts undergo a rigorous screening process after which only 2% of grafts are considered for final use.¹⁷ These allografts are initially rinsed with a light surfactant, which removes the blood, lipid, and cellular components. This is followed by an antibiotic solution that removes contaminants. After which these grafts are tested for microbes and sealed in temperatures ranging from −40°C to −80°C, allowing them to be aseptic.⁷ They have the advantage of no donor site morbidity without the increased risk for resorption. There is a higher cost associated with fresh frozen costal cartilages due to added costs of transportation and storage, which require dry ice and a noncommercial freezer.⁷ This is partly ameliorated with decreased operative times, favorable risk characteristics, and long-term result reliability.⁵ However, further studies need to be conducted to assess the long-term feasibility of fresh frozen costal cartilages on a mass scale, in regard to cost, convenience, and having these grafts readily available.

In the United States, fresh frozen costal cartilage is typically provided by manufacturers such as MTF Biologics, but the studies included in this review did not specify alternative sources.¹⁷ Storage requires specialized freezers (−40°C to −80°C).⁷ High-volume practices may benefit from maintaining an inventory, whereas low-volume practices can order grafts as needed, with unused grafts sometimes stored for future use, though this may incur additional fees. The included studies did not provide specific cost data or comparisons with autologous or irradiated grafts, highlighting the need for future studies to assess cost-effectiveness.

Our studies show that fresh frozen cadaveric grafts have a significantly low incidence of complications with a 4.4% rate of total complications, making them safe for rhinoplasty. The outcome rates of specific complications, including warping, infection rate, revision surgery, and resorption rates, are comparable to those that were produced by Vila et al,¹⁸ who performed a meta-analysis comparing autologous and homologous irradiated costal cartilage. Our subgroup analysis showed that studies that included patients with either primary or revision rhinoplasty patients had higher complications than studies that only included revision rhinoplasty patients. This may in part be accounted for by the fact that the majority of the studies in the exclusively revision rhinoplasty group had shorter or unreported follow-up times.

The limitations of this study are that there are no controls to compare the incidence of complications between the different types of grafts used. This could be overcome by a study comparing the incidence of complications among autologous, homologous irradiated, and fresh frozen cadaveric grafts allowing surgeons to choose the grafts based on the case presented. Furthermore, the studies included in our meta-analysis did not consistently report the sourcing of the fresh frozen cadaveric rib graft. Therefore, we cannot confirm whether all grafts were from the same distributor. This lack of consistency may have introduced variability in product quality and preparation methods. Given the potential variability in product sources, we acknowledge that the comparability between studies may be affected. Future studies should aim to standardize the graft preparation and sourcing to reduce heterogeneity in outcomes.

Moreover, the studies involved had a relatively small sample size and a short mean follow-up time of 10.9 months, out of which 2 studies had a very short follow-up time and unreported follow-up, respectively. We tried to address this by conducting a subgroup analysis that showed that longer follow-up times correlated to a statistically significant increase in total complications, which is scientifically accurate because complications such as warping usually appear after a 6-month period. Further studies need to be done in a larger population with a longer follow-up to better assess the safety and efficacy of fresh frozen grafts.

Finally, the cost of fresh frozen cadaveric rib grafts is an important consideration for surgeons, particularly when balancing the expense with the potential benefit of reduced operative time. However, none of the included studies provided specific cost data or direct comparisons to autologous or irradiated grafts. Surgeons typically have the option to order grafts in precise quantities tailored to each case, and unused grafts can sometimes be stored for future use, though this may involve additional fees. Future studies should provide more detailed cost comparisons to guide clinical decision-making.

CONCLUSIONS

Our systemic review and meta-analysis concluded that frozen cadaveric rib grafts can be used in primary or revision rhinoplasty with good outcomes and comparable complications to current graft sources. Moreover, this donor cartilage has the advantage of no added donor site morbidity compared with autologous grafts and decreased resorption rates compared with homologous irradiated grafts. Although these grafts seem to be a viable alternative, further studies with extended follow-up are needed to fully assess their long-term complication rates and efficacy compared with other graft materials.

DISCLOSURE

The authors have no financial interest to declare in relation to the content of this article.