Management of Flap Failure After Head and Neck Reconstruction: A Systematic Review and Meta-analysis

Abstract

Objective

To systematically review management of flap loss in head and neck construction with free tissue transfer as compared with locoregional flap or conservative management.

Data Sources

Medline, Embase, Scopus, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and ClinicalTrials.gov were searched up to October 2019.

Review Methods

Candidate articles were independently reviewed by 2 authors. Articles were considered eligible if they included adequate reporting of flap management after flap loss and outcomes for survival of reconstruction, length of hospitalization, and perioperative complications.

Results

A total of 429 patients had acute flap failure in the perioperative period. The overall success with a secondary free flap was 93% (95% CI, 0.89-0.97; n = 26 studies, I² = 12.8%). There was no difference in hospitalization length after secondary reconstruction between free tissue transfer and locoregional flaps or conservative management (relative risk of hospitalization ≥2 weeks, 96%; 95% CI, 0.80-1.14; n = 3 studies, I² = 0). The pooled relative risk of perioperative complications following free tissue transfer was 0.60 when compared with locoregional flap or conservative management (95% CI, 0.40-0.92; n = 5 studies, I² = 0).

Conclusion

Salvage reconstruction with free tissue transfer has a high success rate. Second free flaps following flap failure had a similar length of hospitalization and lower overall complication rate than locoregional reconstruction or conservative management. A second free tissue transfer, when feasible, is likely a more reliable and effective procedure for salvage reconstruction.

Keywords

microvascular free flap free flap failure free tissue transfer free tissue transfer failure head and neck reconstruction management of failed free flap management of failed free tissue transfer head and neck reconstructive surgery free flap salvage

Over the last 3 decades, free tissue transfer has become the gold standard for reconstruction of most major complex head and neck defects, as this approach optimizes function and cosmesis.^1,2 Free tissue transfer has been shown to generally have similar success rates, in terms of flap survival, when compared with regional and local flaps.^3-5 The average success rate at most large institutions for free tissue transfer is 95%.^6,7 While many studies evaluate risk factors associated with flap failure (eg, limited operative experience, perioperative decision making, and prior radiation therapy), few investigate the subsequent management after failed flaps.^3,8 When flap failure does occur, there is no consensus on whether these cases should be managed with a second free tissue transfer as opposed to a more conservative approach (ie, locoregional flap, skin grafts, secondary intention).

The reconstructive paradigm provides a framework for the surgeon to evaluate management of flap failure, with the options being second free tissue transfer, regional flap, local tissue rearrangement, secondary intention, and skin grafting. This paradigm does not provide an algorithm to manage patient-specific cases in the setting of flap failure. At the time of flap failure, the surgeon must balance the tissue requirements of the defect to restore function and form against the patient’s ability to tolerate additional surgery. Thus, there may be a shift in prioritizing function and cosmesis, as operative morbidity from surgery may outweigh the original disease process. Data regarding management of free flap failure are limited to institutional retrospective cohort studies,^4,9-17 case series,^18-37 and case reports.^38,39 Bender-Heine et al recently performed the first multi-institutional retrospective review on management of flap failures and designed various algorithms to manage flap failures.⁹ Even though the generalizability of the algorithms was limited by the low number of flap failures across the institutions, this study was an important contribution that highlighted the need for greater reporting of management of flap failures and emphasized the importance of universal reporting standards.

The objective of this systematic review and meta-analysis was to qualitatively and quantitatively assess whether a second free flap can be considered a safe and reliable procedure for management of free flap failure. We then sought to investigate differences in hospitalization and complications among the various approaches for management of flap failure. We hypothesized that free flap reconstruction would have a similar risk of failure as regional flap or local tissue rearrangement after initial free flap failure.

Methods

The PRISMA guidelines (Preferred Reporting Items for Systematic Reviews and Meta-analyses) were followed for this study. This study was exempt from the Washington University Human Research Protection Office, as it used data from published literature. Studies were selected per the PICOS format:

Population: patients with free flap loss for head and neck reconstruction

Intervention: salvage reconstruction of free flap loss with second free tissue transfer

Comparator: management of flap loss with local tissue rearrangement, regional flap, or conservative management (ie, skin grafting, secondary intention)

Outcome: survival of reconstruction within 30 days

Study design: retrospective cohort studies, case series, and case reports with a minimum mean or median follow-up of 30 days after management of free flap loss

The survival of nonvascularized reconstructive options (ie, skin grafting or secondary intention) was based on wound stability or failure to heal over a 3-month period without additional surgery. The secondary outcomes of interest were length of hospitalization and perioperative complications within 30 days after management of reconstruction failure. A minimum follow-up of 30 days was used, as free flap failure occurs most commonly within the first month after reconstruction.

The published literature was searched with strategies created by a medical librarian (A.C.H.) for outcomes after management of free failure for head and neck defects. The search strategies were established with a combination of standardized terms and keywords implemented in Ovid Medline (1946-2019), Embase (1947-2019), Scopus (1823-2019), Cochrane Central Register of Controlled Trials, Database of Abstracts of Reviews of Effects, Cochrane Database of Systematic Reviews, and ClinicalTrials.gov. The search was completed in October 2019. Results were exported to EndNote for a total of 452 articles. The automatic duplicate finder in Endnote was used, and 164 duplicates were assumed to be accurately identified for a total of 302 unique citations. An additional search was performed through the article references. Further screening and review were performed to remove articles (n = 199) that did not focus on the questions of interest. Full search strategies are provided in Supplemental Appendix S1 (available online). In total, 103 articles were identified and entered into a spreadsheet. Figure 1 depicts the selection process.

Study Selection

All stages of the review (title, abstract, full-text articles, and data extraction) were performed in duplicate by 2 independent reviewers (A.W. and P.P.). Titles and abstracts were initially reviewed for study inclusion. At this level, a study was excluded if it was non-English, was a review article, included an abstract only, or focused on nonhuman research. Then, full-text articles were reviewed. At this point, a study was excluded if it had inadequate reporting of the outcomes of interest (complication rate at 30 days) or a mean or median follow-up <30 days. Each reviewer was initially blinded to the other’s results. Any discrepancies were resolved by discussion between the reviewers.

Data Collection Process

A data collection form was created, tested on the initial 10 articles, and refined accordingly. Information was extracted from each study for the following variables: (1) inclusion and exclusion factors, (2) patient characteristics (age, sex, length of follow-up, indication for surgery, radiation status), (3) features of initial surgery (free flap failed, etiology of failure, location of defect), (4) type of second reconstruction (ie, free tissue transfer and flap type, regional flap, local tissue rearrangement, skin grafting, secondary intention), and (5) type of outcome measure (survival of reconstruction, hospitalization length, and 30-day complications).

Summary Measures and Statistical Analysis

Our primary outcome was survival of second free flaps in patients with initial free flap failure. Secondary outcome measures were length of hospitalization and perioperative complications. Perioperative complications included recipient site, donor site, and medical complications. Recipient site complications were fistula, hematoma, partial flap loss, and wound infection. Donor site complications included seroma, hematoma, wound dehiscence, and wound infection. Medical complications were pneumonia, deep venous thrombosis, cerebral vascular accident, myocardial infarction, pulmonary embolism, and renal failure. We used descriptive statistics to describe the study population, hospitalization length, perioperative complications, and survival outcomes. Given that all of the studies were observational, we anticipated significant heterogeneity across them. We accordingly used a random effects meta-analysis model a priori to summarize the survival proportion of free tissue transfer from each study and to calculate the survival rate from all studies. The fixed effect model was used for length of hospitalization and perioperative complications, as there was limited heterogeneity across the studies (I² = 0%). Heterogeneity was calculated via I², with 25%, 50%, and 75% as respective cutoffs for low, moderate, and high heterogeneity. A funnel plot was constructed to assess for publication bias, and the Harbord test was utilized to assess for small-study effects. All analysis was performed with Stata version 16 (StataCorp).

Quality Assessment

Assessment of bias was independently performed by 2 authors (A.W. and P.P.) using the MINORS criteria (Methodological Index for Non-randomized Studies), which has a maximum sum score of 16 for noncomparative studies and 24 for comparative studies ( Table 1 ).

Table 1.

Quality and Risk of Bias as Assessed With the MINORS Tool.^a

Reference	Year	Clearly stated aim	Inclusion of consecutive patients	Prospective data collection	Population defined	Subjects comparable	Statistical analysis described	Appropriate endpoints	Unbiased assessment of endpoints	Follow-up appropriate	Loss to follow-up <5%	Individual patient information	MINORS sum score
Asai³⁸	2010	1	1	0	2	1	0	1	1	2	2	+	11
Belli¹⁸	1995	1	1	0	2	1	0	1	1	2	2	+	11
Bender-Heine⁹	2021	2	1	1	1	1	0	2	2	2	2	+	14
Camuzard¹¹	2017	1	2	1	2	1	0	1	2	2	2	–	14
Celik²⁰	2002	1	1	0	2	1	0	1	1	2	2	–	11
Chiu¹²	2017	2	2	1	2	2	0	2	2	2	2	–	17
Coleman⁴	1987	2	2	1	2	2	0	2	2	2	2	+	17
Corbitt¹⁰	2014	2	2	1	2	2	2	2	2	2	2	+	19
David¹³	2011	2	2	1	2	2	0	2	2	2	2	–	17
Dean²¹	2010	1	1	0	2	1	0	1	1	2	2	+	11
Dionyssopoulos²²	2012	1	1	0	2	1	0	1	1	2	2	+	11
Fischborn³⁹	2011	1	2	1	2	1	0	1	2	2	2	+	14
Giordano²³	2016	1	1	0	2	1	0	1	1	2	2	+	11
Hanson²⁴	2007	1	1	0	2	1	0	1	1	2	2	+	11
Havlik¹⁹	1994	1	1	0	2	1	0	1	1	2	2	+	11
Heather²⁵	2012	2	1	1	1	1	0	2	2	2	2	+	14
Ho¹⁴	2012	2	2	1	2	2	2	2	2	2	2	–	19
Inbal²⁶	2015	1	1	0	2	1	0	1	1	2	2	+	11
Kucur²⁷	2016	1	1	0	2	1	0	1	1	2	2	–	11
Kuo²⁸	2010	1	1	0	2	1	0	1	1	2	2	+	11
Lyons²⁹	2013	2	2	1	2	2	2	2	2	2	2	+	19
Okazaki¹⁵	2007	2	2	1	2	2	2	2	2	2	2	+	19
Pohlenz⁵	2007	2	2	1	2	2	0	2	2	2	2	–	17
Revenaugh³⁰	2014	1	2	1	2	1	0	1	2	2	2	+	14
Ross¹⁶	2012	2	2	1	2	2	2	2	2	2	2	–	19
Shpitzer³¹	1997	1	1	0	2	1	0	1	1	2	2	+	11
Smith³²	2005	2	2	1	2	2	2	2	2	2	2	–	19
Uǧurlu³³	2004	1	1	0	2	1	0	1	1	2	2	+	11
Upton³⁴	2008	1	1	0	2	1	0	1	1	2	2	+	11
Urken³⁵	1993	1	1	0	2	1	0	1	1	2	2	+	11
Wei³⁶	2003	1	1	0	2	1	0	1	1	2	2	+	11
Wei¹⁷	2001	2	2	1	2	2	2	2	2	2	2	–	19
Yeh³⁷	2019	1	1	0	2	1	0	1	1	2	2	+	11

Abbreviation: MINORS, Methodological Index for Non-randomized Studies.

Items are scored 0 (not reported), 1 (reported but inadequate), or 2 (reported and adequate). Individual patient data are scored as present (+) or not present (–).

Results

Characteristics of the Studies

The search strategy yielded 33 studies for qualitative analysis ( Figure 1 ). These studies were all retrospective case series or case reports. Twenty-five studies included data on management of free flap failure with second free flaps. Of the studies, 8 compared management of free flap failure with second free flaps and locoregional flaps or conservative management. Of these 8 studies, 5 reported perioperative complications and 3 described hospitalization length. The details of the individual studies are presented in Table 2 .

Table 2.

Summary of the Included Studies.

		No. of free flaps		Study		Location of defect for failed flap, No. (%)
Reference	Year	Total	Failed	Length, y	Type	Mandible	Pharyngoesophagus	Parotid / temporal bone	Scalp	Oral cavity	Maxillary	Preoperative chemoradiation
Asai³⁸	2010	2	2		Case report					2 (100)
Belli¹⁸	1995	31	3	3	Case series
Bender-Heine⁹	2021	3740	118	13	Retrospective		26 (23.2)			66 (58.9)	20 (17.9)	22
Corbitt¹⁰	2014	3090	40	12	Retrospective	12 (30.0)	5 (12.5)	2 (5.0)	4 (10)	7 (17.5)	10 (25.0)
Camuzard¹¹	2017	77	7	12	Retrospective					7 (100)
Celik²⁰	2002	27	1	10	Case series					1 (100)
Chiu¹²	2017	1258	34	13	Retrospective							7
Coleman⁴	1987	96	13	10	Retrospective		13 (100)					4
David¹³	2011	312	22	7	Retrospective	1 (4.5)				21 (95.5)
Dean²¹	2010	65	1	7	Case series
Dionyssopoulos²²	2012	20	1	10	Case series		1 (100)
Fischborn³⁹	2011	1	1		Case report		1 (100)
Giordano²³	2016	14	2	3	Case series		2 (100)
Hanson²⁴	2007	23	2	9	Case series		2 (100)
Havlik¹⁹	1994	7	1		Case series					1 (100)
Heather²⁵	2012		6	4	Case series	1 (16.7)			1 (16.7)	2 (33.3)	2 (33.3)	2
Ho¹⁴	2012	851	41	10	Retrospective
Inbal²⁶	2015	6	1		Case series					1 (100)		1
Kucur²⁷	2016	260	9	4	Case series
Kuo²⁸	2010	20	1	2	Case series	1 (100)
Lyons²⁹	2013	30	2	5	Case series	2 (100)
Okazaki¹⁵	2007	502	19	12	Retrospective	3 (15.8)	4 (21.1)			8 (42.0)	4 (21.1)	13
Pohlenz⁵	2007	202	6	7	Retrospective
Revenaugh³⁰	2014	51	1		Case series	1 (100)						1
Ross¹⁶	2012	1475	12	17	Retrospective
Shpitzer³¹	1997	47	4	3	Case series	4 (100)
Smith³²	2005	263	9	15	Case series					9 (100)
Uǧurlu³³	2004	9	3	3	Case series	1 (33.3)		1 (33.3)		1 (33.4)		2
Upton³⁴	2008	165	1	30	Case series					1 (100)
Urken³⁵	1993	26	3	5	Case series				1 (33.3)		2 (66.7)	1
Wei³⁶	2003	44	1	2	Case series	1 (100)
Wei¹⁷	2001	1235	42	8	Retrospective
Yeh³⁷	2019	81	3	9	Case series	3 (100)

Quality Assessment

Quality assessment is shown in Table 1 for all articles in the systematic review and meta-analysis. The 26 studies included individual patient data for reconstruction survival outcomes. Several studies were individual case reports or case series with comprehensive descriptions of the reconstruction outcomes. The 26 studies in the meta-analysis had clear goals, detailed descriptions of the populations, appropriate summary of the interventions, and adequate endpoints.

Systematic Review

The characteristics of the individual studies are shown in Tables 3 and 4 . A total of 14,107 free flap outcomes were reviewed in the 33 studies for qualitative analysis, and 429 failed flaps were in our descriptive review of management of free flap failures. The median study length for case series and retrospective cohort studies was 9 years (range, 1 month–30 years). All 33 studies provided descriptions of the type of flap that had failed, the type of reconstruction used for management, and the success of management of free flap failure within at least 30 days.

Table 3.

Studies With Type and Etiology of Free Flap Failure.^a

		Free flap failed									Etiology of failure
Reference	Year	ALT	Iliac crest	Fibula	RFFF	Rectus abdominis	LD	Jejunum	Groin	Scapula	Infection	Flap design / harvest	Pedicle compression	Kinked pedicle	Hemorrhage	HD	Fistula	HPN	Venous congestion	IJV thrombosis	Unclear
Asai³⁸	2010					1 (100)										2 (100)
Bender-Heine⁹	2021	26 (28.0)		39 (41.9)	28 (30.1)									47 (64.4)					26 (35.6)
Corbitt¹⁰	2014	15 (37.5)		12 (30.0)	3 (7.5)	3 (7.5)	3 (7.5)	2 (5.0)	2 (5.0)		0 (0)	6 (18.8)	5 (15.6)	4 (12.5)	3 (9.4)	2 (6.3)	2 (6.3)	1 (3.1)		1 (3.1)	8 (25)
Camuzard¹¹	2017			7 (100)
Havlik¹⁹	1994				1 (100)																1 (100)
Celik²⁰	2002			1 (100)																	1 (100)
Coleman⁴	1987							6 (100)					3 (33.3)		1 (11.1)		1 (11.1)	1 (11.1)			3 (33.3)
David¹³	2011			9 (40.9)	13 (59.1)							1 (4.8)	1 (4.8)	1 (4.8)	1 (4.8)	1 (4.8)	1 (4.8)		10 (47.5)		5 (23.7)
Dean²¹	2010	1 (100)																			1 (100)
Dionyssopoulos²²	2012							1 (100)													1 (100)
Fischborn³⁹	2011			1 (100)									1 (100)
Heather²⁵	2012	1 (16.7)	1 (16.7)		1 (16.7)	1 (16.6)	1 (16.6)			1 (16.7)					1 (16.7)			3 (50.0)			2 (33.3)
Ho¹⁴	2012	3 (8.8)	10 (29.4)	4 (11.8)	15 (44.1)		2 (5.9)
Inbal²⁶	2015			1 (100)															1 (100)
Kuo²⁸	2010																		1 (100)
Lyons²⁹	2013						1 (50)			1 (50)					2 (100)
Okazaki¹⁵	2007	2 (10.5)	1 (5.3)	1 (5.3)	6 (31.6)	3 (15.8)	1 (5.3)	4 (21.1)		1 (5.3)				13 (68.4)					6 (31.6)
Pohlenz⁵	2007		1 (16.7)	2 (33.3)	1 (16.7)		2 (33.3)												6 (100)
Revenaugh³⁰	2014	1 (100)																			1 (100)
Ross¹⁶	2012	2 (16.7)		4 (33.3)	3 (25.0)	1 (8.3)	2 (16.7)							3 (30.0)					5 (50.0)		2 (20.0)
Shpitzer³¹	1997			4 (100)											2 (50.0)				2 (50.0)
Smith³²	2005				9 (100)
Uǧurlu³³	2004		1 (33.3)		1 (33.4)					1 (33.3)
Upton³⁴	2008				1 (100)											1 (100)
Urken³⁵	1993					1 (33.3)				2 (66.7)				1 (50.0)	1 (50.0)
Wei³⁶	2003	1 (100)													1 (100)

Abbreviations: ALT, anterolateral; HD, hypercoagulable disorder; HPN, hypotension; IJV, internal jugular vein; LD, latissimus dorsi; RFFF, radial forearm free flap.

Data are presented as No. (%).

Table 4.

Management of Free Flap Failure and Success Rate of Salvage Reconstruction.^a

		Second free flap								Locoregional Flap			Conservative			Success
Reference	Year	ALT	Fibula	RFFF	Rectus abdominis	Latissimus dorsi	Jejunum	Gastric pullup	Scapula	SC flap	Other	Pectoralis major	Obturator	Primary closure	Secondary intention	Second free flap	Conservative / locoregional
Corbitt¹⁰	2014	11 (37.9)	4 (13.8)	6 (20.7)	3 (10.3)	4 (13.8)			1 (3.4)			7 (63.6)	3 (27.3)	1 (9.1)	1	27 (93.1)	11 (100)
Camuzard¹¹	2017		4 (100)									3 (100)			0	4 (100)	3 (100)
Asai³⁸	2010				1 (100)							1 (100)				0	1 (100)
Belli¹⁸	1995					2 (100)						1 (100)				2 (100)	1 (100)
Bender-Heine⁹	2021															54 (91.5)	63 (100)
Havlik¹⁹	1994											1 (100)					1 (100)
Camuzard¹¹	2017		4 (100)									3 (100)				4 (100)	3 (100)
Celik²⁰	2002											1 (100)					1 (100)
Chiu¹²	2017	2 (28.5)		3 (42.9)		1 (14.3)	1 (14.3)					7 (100)				7 (100)	7 (100)
David¹³	2011		3 (30.0)	7 (70.0)								8 (72.7)	1 (9.1)	2 (18.2)		9 (90.0)	11 (100)
Dean²¹	2010			1 (100)											1 (100)	1 (100)	1 (100)
Dionyssopoulos²²	2012											1 (100)					1 (100)
Fischborn³⁹	2011									1 (100)							1 (100)
Giordano²³	2016									2 (100)						2 (100)
Hanson²⁴	2007						1 (50.0)	1 (50.0)								1 (50.0)
Heather²⁵	2012			1 (16.7)	2 (33.3)				2 (33.3)		1 (16.7)					5 (100)	1 (100)
Ho¹⁴	2012		1 (4.3)	14 (60.9)		6 (26.1)			2 (8.7)			8 (44.4)	3 (16.7)	7 (38.9)		23 (100)	18 (100)
Inbal²⁶	2015		1 (100)													1 (100)
Kucur²⁷	2016											9 (100)					9 (100)
Kuo²⁸	2010		1 (100)													1 (100)
Lyons²⁹	2013											2 (100)					0
Okazaki¹⁵	2007	1 (14.3)		1 (14.3)	2 (28.5)	1 (14.3)	2 (28.6)					3 (100)				6 (85.7)	3 (100)
Pohlenz⁵	2007		1 (50)			1 (50)						1 (11.1)			8 (88.9)	2 (100)	9 (100)
Revenaugh³⁰	2014	1 (100)													3 (100)	1 (100)	3 (100)
Ross¹⁶	2012	2 (25)		1 (12.5)	1 (12.5)	2 (25)			2 (25)			3 (100)				5 (62.5)	3 (100)
Shpitzer³¹	1997		3 (100)												1	2 (66.7)	0
Smith³²	2005			1 (100)							1 (20)	3 (60)			1 (20)	1 (100)	5 (100)
Uǧurlu³³	2004										3 (42.9)				4 (57.1)		7 (100)
Upton³⁴	2008										1 (100)						1 (100)
Urken³⁵	1993				1 (33.4)	1 (33.3)			1 (33.3)						1 (100)	3 (100)	1 (100)
Wei³⁶	2003											1 (100)					1 (100)
Yeh³⁷	2019			1 (50)					1 (50)			1 (100)				2 (100)	1 (100)

Abbreviations: ALT, anterolateral; RFFF, radial forearm free flap; SC, supraclavicular.

Data are presented as No. (%).

Length of hospitalization following management of flap failure, comparing second free flap with locoregional reconstruction, was discussed as a categorical variable (<2 and ≥2 weeks) in 3 studies.^9,15,17 Perioperative complications were discussed in 5 studies comparing second free flap and locoregional reconstruction. There was heterogeneous reporting of length of hospitalization and perioperative complications.

Of the 33 studies in the qualitative analysis, 61.1% of flap failures were located within the oral cavity soft tissue (181/296). Of the 8 studies that reported preoperative chemoradiation status, 26.1% of patients who had failed flaps received preoperative chemoradiation (53/203). Of 26 studies that discussed details of flap failure, including type of failed flap and etiology, 29.0% of the flaps that failed were radial forearm free flaps (54/186), and 24.7% were fibula free flaps (46/186). Of the 22 studies that discussed etiology of initial free flap failure, 29.3% of flaps failed due to venous congestion (57/195), and 35.4% of flaps failed due to kinked pedicle (69/195).

Meta-analysis

Of the 33 studies, 26 were selected for meta-analysis. The excluded 7 studies included management of flap failure with locoregional flap or conservative management and did not manage failures with second free flap. Meta-analysis of 280 patients who underwent salvage free flap reconstruction after initial flap failure revealed a pooled survival rate of 93% (95% CI, 89%-97%; Figure 2 ). Statistical heterogeneity was low for survival of free flap after free flap failure (I² = 12.8%)

Meta-analysis of 166 patients in 3 studies with failed free flaps who underwent second free flap reconstruction or locoregional reconstruction showed similar hospitalization lengths after the second procedure. Hospitalization length ≥2 weeks between second free flap and locoregional reconstruction showed a pooled relative risk of 0.96 (95% CI, 0.80-1.14; P = .63; Figure 3 ). Statistical heterogeneity was low for hospitalization length after the second procedure between free flap and locoregional reconstruction (I² = 0%).

Meta-analysis of 205 patients in 5 studies with failed free flap who underwent reconstruction with second free flap or locoregional reconstruction showed fewer perioperative complications after second free flap. The pooled relative risk of perioperative complications after second free flap was 0.60 when compared with locoregional flaps (95% CI, 0.40-0.92; P = .02; Figure 4 ). Statistical heterogeneity was also low for perioperative complications after the second procedure (I² = 0%).

Publication Bias

Publication bias was assessed by a funnel plot ( Figure 5 ). The Harbord test was unable to exclude a symmetric distribution of publications, suggesting a low risk of publication bias (P = .61).

Discussion

The standard of care for reconstruction of large defects in the head and neck is free tissue transfer with closely matched tissue, with the goal of optimizing cosmesis and functional outcomes. As a result of advancements in technology and surgical techniques, free tissue transfer has become an option at nearly all major academic institutions in the developed world. However, free flap failure can still occur, even in the most experienced hands. Over the last 3 decades, a significant amount of literature has focused on patient factors and comorbidities that are likely to lead to free flap failure; however, a predictable relationship has not been identified.^40-43 Reconstructive efforts in the setting of free flap failure, including secondary free flaps, have been less well studied. Data are limited to retrospective institutional experience, case series, and case reports. To the best of our knowledge, this is the first systematic review and meta-analysis analyzing published literature on this topic.

In cases of acute free flap failure, a difficult decision must be made about how to reconstruct the defect after the cathartic process of flap removal. Naturally, there may be reluctance from the surgeon and patient to attempt a second free flap, especially if no clear cause for failure was identified. A critical question is whether a surgeon should (1) go down the reconstructive ladder after free flap failure when other methods were thought to be less acceptable for the original procedure⁴⁴ or (2) confidently proceed with the second-best option, even if that is a second free flap.

In our systematic review, we found that the rate of failure after secondary reconstruction, whether locoregional or free flap, is quite low (6.3%). The pooled survival rate for second free flap after free flap failure was 93% (95% CI, 0.89-0.97), which is quite similar to survival rates for primary free tissue transfer. These success rates with second free flap reconstruction suggest that second free flaps can be a highly reliable solution for reconstruction in the setting of an initial free flap failure and should be considered if the patient can tolerate additional surgical attempts and anesthesia.

The complication rate for patients who underwent a subsequent free flap attempt was lower than that among those who underwent locoregional reconstruction (12.7% vs 19.5%). However, medical complications after surgery were largely underreported in most of the studies discussed here. Corbitt et al found a high medical complication rate (eg, pneumonia, deep vein thrombosis, cerebrovascular accident, myocardial infarction, pulmonary embolism, or renal failure) in their cohort who underwent second free flap reconstruction (21.4%).¹⁰ However, this risk was still lower for free flaps when compared with locoregional flaps or conservative management. This finding was similar to what we found in our review where 30-day complications—as defined by recipient loss or complications, donor site infection or complications, or medical complications—were lower for free flaps as opposed to locoregional flaps (pooled relative risk, 0.60; 95% CI, 0.40-0.92; P = .02). The most common complications in our systematic review were fistulas and wound infections, which were more common in the cohort undergoing locoregional flap or conservative management. We suspect that this observation is due to the fact that the appropriate reconstruction for the patients who underwent locoregional reconstruction or conservative management after free flap failure was a free flap, as this was intended by the original procedure. Thus, although meant to reduce perioperative risk, more conservative approaches (ie, a lower rung on the reconstruction ladder) may paradoxically lead to more complications due to inappropriate coverage and poor function of alternative reconstruction options.

We found that the most common etiology for a flap failure was kinked pedicle (35.4%), with venous congestion occurring 29.3% of the time. Many prior studies were unable to identify the etiology of flap failure, as the artery and vein were thrombosed once flap compromise was detected.^3,10 It is likely that infection, hemorrhage, and fistula may be common causes of flap failure; however, identification of these as the true cause of flap failure is difficult and likely underreported since these processes are more complex to identify. Preoperative radiation may also contribute to increasing the risk of flap failure. Herle et al showed that preoperative radiation increases the risk of free flap failure and other complications.⁸ This is thought to be related to macro- and microscopic changes within the vascular anatomy.^43,45,46 In this review, we found that 26.1% of patients who had failed flaps received preoperative chemoradiation.

Once a flap has failed, the ideal approach is not always clear, and choosing between a free and regional flap can be a difficult decision. In a retrospective review across 4 centers, Bender-Heine et al emphasized that the recipient site was the most important factor for management of initial flap failure, where a second free flap is preferred but local or regional flaps may be required based on the patient’s comorbidities, circumstances of flap loss, and particular recipient site.⁹ In this systematic review, the majority of patients (57.1%) received a second free flap following the first failure, and 42.9% underwent a locoregional flap or other conservative measure, such as skin grafting or healing by secondary intention. Previous studies suggested that even in the setting of acute flap failure, a second free flap is still more effective and reliable in head and neck reconstruction than a regional flap or conservative management.^7,17,47 However, the nuances of that decision process are not well represented in a systematic review and meta-analysis of this nature. Factors that surgeons generally consider for salvage reconstruction include medical optimization of the patient for a second procedure, family discussion, and identification of potential reversible causes for initial flap failure. Success with second free flap in this systematic review was 93%. This likely considers optimizing the patient’s medical problems prior to the second procedure, reassessing the optimal approach for reconstruction, and then deciding whether a second free flap would be the ideal approach. The results of this study confirm that a free flap should be considered a viable option after most cases of free flap loss. This results in likely the best cosmesis and function with low complication rates and equivalent hospitalization rates. Although the high success rate after a subsequent free flap has been reported,^7,17,47 this is the first study to confirm this success rate through a systematic review and meta-analysis.

This study has several important limitations. All studies within this systematic review and meta-analysis were retrospective, which can lead to a significant selection bias regarding why a surgeon chose a specific reconstructive approach over another. For example, surgeons are more likely to select second free flaps in healthier patients, while patients with significant comorbidities are more likely to undergo treatment options that are conservative (ie, locoregional flaps). This is difficult to account for within a retrospective study but is a major limitation when drawing conclusions. We acknowledge that the nature of this study has limited applicability for a meaningful comparison between free flaps and locoregional flaps due to the lack of direct comparative studies in the literature. Despite this limitation, heterogeneity was low (I² = 12.8%) in our final meta-analysis. Free flap failure is a rare complication of free tissue transfer; thus, there is a limited number of studies discussing management of free failure. Furthermore, there is a negative stigma toward discussing free flap failure among head and neck surgeons. Thus, most of our studies had sample sizes of <100 patients. Another limitation was the significant heterogeneity in how hospitalization length after secondary reconstruction was reported—as a dichotomous variable (as performed in the meta-analysis here) or as a mean with standard deviation. Importantly, we were unable to control for confounders and assess risk factors that would lead to secondary reconstruction failure after initial free flap failure because of inconsistent reporting of data. The lack of sufficiently reported data limited our ability to perform subgroup analyses on the various types of reconstruction. Additionally, the studies were performed over 4 decades where surgical technique and available technologies have significantly affected success rates with free tissue transfer. Even though the success of second free flaps is supported by this systematic review, the nature of this study does not account for the preoperative decision making (eg, quality of life and comorbidities) that may have led to the final decision of performing a free flap as opposed to a locoregional or conservative management approach.

Conclusion

This is the first systematic review and meta-analysis investigating the outcomes and complications for management of free flap failure in head and neck reconstruction. There was no clinically significant difference of reconstruction survival outcomes or hospitalization length for locoregional reconstruction or conservative management as compared with second free flap after initial free flap failure. Pooled complication rate data suggest a lower complication rate with free tissue transfer versus locoregional flaps or conservative management. Large multicenter studies are necessary to validate these findings before considering universal algorithms for the management of free flap failures. The >90% success rates of salvage reconstructions with free flaps after flap failure and higher complication rates associated with locoregional reconstructions suggest that most patients will likely benefit with a second free tissue transfer.

Supplemental Material

sj-docx-1-oto-10.1177_01945998211044683 – Supplemental material for Management of Flap Failure After Head and Neck Reconstruction: A Systematic Review and Meta-analysis

Supplemental material, sj-docx-1-oto-10.1177_01945998211044683 for Management of Flap Failure After Head and Neck Reconstruction: A Systematic Review and Meta-analysis by Amit Walia, Jake J. Lee, Ryan S. Jackson, Angela C. Hardi, Craig A. Bollig, Evan M. Graboyes, Joseph Zenga, Sidharth V. Puram and Patrik Pipkorn in Otolaryngology–Head and Neck Surgery

Footnotes

Author Contributions

Amit Walia, design, acquisition, analysis, writing, revising; Jake J. Lee, analysis, revising; Ryan S. Jackson, analysis, revising; Angela C. Hardi, design, acquisition; Craig A. Bollig, analysis, revising; Evan M. Graboyes, analysis, revising; Joseph Zenga, analysis, revising; Sidharth V. Puram, analysis, revising; Patrik Pipkorn, design, acquisition, analysis, writing, revising

Disclosures

Competing interests: None.

Sponsorships: None.

Funding source: Amit Walia is supported by institutional training grant T32DC000022, National Institute on Deafness and Other Communication Disorders, National Institutes of Health.

ORCID iD

Amit Walia

Supplemental Material

Additional supporting information is available in the online version of the article.

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