A persistent challenge that has limited access and delivery of digit replantation surgery is timing, as ischemia time has traditionally been considered an important determinant of success. However, reports that the viability of amputated digits decreases after 6 hours of warm ischemia and 12 hours of cold ischemia are largely anecdotal. This review evaluates the quality and generalizability of available evidence regarding ischemia times after digit amputation and reported outcomes of “delayed” replantation. We identify substantial limitations in the literature supporting ischemia time cutoffs and recent evidence supporting the feasibility of delayed digit replantation. The current treatment approach for amputation injuries often necessitates transfers or overnight emergency procedures that increase costs and limit availability of digit replantation nationwide. Evidence-based changes to digit replantation protocols could lead to broader availability of this service, as well as improved care quality.
Key words
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Dawn M. LaPorte, MD, has no relevant conflicts of interest to disclose.
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Dawn M. LaPorte, MD, has no relevant conflicts of interest to disclose. The editorial and education staff involved with this journal-based CME activity has no relevant conflicts of interest to disclose.
Learning Objectives
Upon completion of this CME activity, the learner will understand:
- •The evidence regarding ischemia times after digit amputation.
- •Limitations of studies regarding impact of ischemia time on replantation success.
- •The evidence supporting the feasibility of delayed digit replantation.
Deadline: Each examination purchased in 2021 must be completed by January 31, 2022, to be eligible for CME. A certificate will be issued upon completion of the activity. Estimated time to complete each JHS CME activity is up to one hour.
Copyright © 2021 by the American Society for Surgery of the Hand. All rights reserved.
Digit (finger and thumb) replantation requires time, technical expertise, coordination of care, and dedicated patient participation in postoperative therapy to achieve optimal outcomes. One of the persistent challenges limiting broader access and delivery of digit replantation surgery is timing, as ischemia time has traditionally been considered a critical element. This requires emergent transport to the operating room under the premise that a delay decreases the chances of success. However, this has recently been challenged.
Evidence that the viability of amputated digits decreases after 6 hours of warm ischemia and 12 hours of cold ischemia is largely anecdotal.
1
, 2
, 3
, 4
, 5
, 6
, 7
, 8
, 9
There are numerous reports of successful replantation outside of these time constraints, at up to 42 hours of warm ischemia and 94 hours of cold ischemia.10
, 11
, 12
, 13
, 14
, 15
, 16
, 17
, 18
, 19
Despite this, there has been little change to the dogma of ischemia time for digit replantation. It is likely that early studies on replantation care are not entirely applicable to current treatment, due to advances in microsurgical techniques and postoperative monitoring and support. A growing body of literature supports the success and safety of digit replantation after long ischemia times.20
Understanding the true timing requirements for digit replantation will have an impact on how this critical service is delivered. Considering the conflicting evidence in individual manuscripts, this review seeks to evaluate the quality and generalizability of evidence regarding ischemia time after digit amputation and reported outcomes of “delayed” replantation. For this study, MEDLINE and Embase OVID were queried from 1950 to the present. The preservation method and temperature during the ischemia time were noted, if reported. Literature reviews and meta-analyses were reviewed for content, because they contribute to the current understanding.Results From Primary Articles
The 22 applicable studies spanned 1989 to 2019 (Table 1).
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,20
, 21
, 22
, 23
, 24
, 25
, 26
, 27
, 28
, 29
, 30
, 31
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, 33
, 34
, 35
, 36
Of these, 5 reported ischemia times for each replanted digit and 4 included average ischemia times for surviving and nonsurviving groups. Seven studies reported a negative impact of ischemia time on replant success, though the ischemia time stratification differed among them.4
,21
,23
,29
,32
,33
,36
Five of these did not include the preservation method, and 2 provided a warm ischemia time only. None of the 7 studies associating longer warm ischemia times with replant failure reported individual ischemia times, preventing any composite review or meta-analysis. Seven studies reported no significant impact of ischemia time on survival.20
,26
, 27
, 28
,30
,31
,35
Five of these did not include individual ischemia times, and 4 did not include the method of preservation.Table 1Summary of All Studies Identified for Qualitative Review, Including Variation in Reported Outcomes and a Summary of Results
| Author | Year | Name | Journal | Total Digits | Is Ischemia Time Significant? | Report Individual Ischemia Times? | Specify Method of Preservation? | Functional Outcomes? | Results (Viable Replants/Total Replants) |
|---|---|---|---|---|---|---|---|---|---|
| Tark et al 21 | 1989 | Replantation and revascularization of hands: clinical analysis and functions results of 261 cases | J Hand Surg Am | 149 | Warm ischemia >13 h greater risk of necrosis than warm ischemia <12 h. No difference between <12 h warm and <12 or >13 h cold ischemia. | No | No | Yes | <12 h warm ischemia: 37/47 (78.7%) <12 h cold ischemia: 37/46 (80.4%) >13 h warm ischemia: 20/29 (69.0%) >13 h cold ischemia: 46/56 (82.1%) <12 h total ischemia: 124/148 (83.8%) >13 h total ischemia: 89/113 (78.8%) |
| Iglesias and Serrano 19 | 1990 | Replantation of amputated segments after prolonged ischemia | Plast Reconstr Surg | 14 | Not addressed | Yes | Temperature only | Yes | 18–24 h warm ischemia: 7/9 (77.8%) 30–48 h total ischemia: 3/4 (75.0%) 56–74 h total ischemia: 0/2 (0%) |
| Baek and Kim 22 | 1992 | Ten-digit and nine-digit replantation (4 cases) | Br J Plast Surg | 38 | Not addressed | No | Temperature only | Yes | 1.5–4 h warm ischemia + 3.2–27 h cold ischemia: 37/38 (97.4%) |
| Zhang et al 16 | 1993 | Five year digital replantation series from the frigid zone of China | Microsurgery | 161 | Not addressed | No | Temperature only | Yes | 2–6 h total ischemia: 61/65 (93.8%) 6–10 h total ischemia: 29/32 (90.6%) 10–12 h total ischemia: 10/12 (83.3%) 24–58 h total ischemia: 7/7 (100%) |
| Arakaki and Tsai 23 | 1993 | Thumb replantation: survival factors and re-exploration in 122 cases | J Hand Surg Br | 81 | Presurgery time >8h greater risk of necrosis than <8h in sharp amputations | No | No | No | <8 h total presurgery time: 50/53 (94.3%) >8 h total presurgery time: 20/27 (74.1%) |
| Kim et al 15 | 1996 | Eight cases of nine-digit and ten-digit replantations | Plast Reconstr Surg | 74 | Not addressed | No | Temperature only | Yes | 0.2–15 h warm ischemia + 3–29 h cold ischemia: 70/74 (94.6%) |
| Waikakul et al 24 | 1999 | The role of allopurinol in digital replantation | J Hand Surg Br | 104 | Not addressed | No | Temperature only | Yes | 20.2–20.4 h average total ischemia: 92/104 (88.5%) |
| Waikakul et al 25 | 2000 | Results of 1018 digital replantations in 552 patients | Injury | 745 | Not addressed | No | No | Yes | Data include subtotal amputations |
| Faivre et al 26 | 2003 | Adjacent and spontaneous neurotization after distal digital replantation in children | Plast Reconstr Surg | 8 | No significant association between ischemia time and replant survival | Yes | Temperature only | Yes | 2.8–9.5 h cold ischemia: 8/8 (100%) |
| Li et al 27 | 2008 | Fingertip replantation: determinants of survival | Plast Reconstr Surg | 211 | No significant association between ischemia time and replant survival | No | Yes | No | <8 h total ischemia: 52/67 (77.6%) 8–16 h total ischemia: 101/124 (81.5%) >16 h total ischemia: 19/20 (95.0%) |
| Lin et al 12 | 2010 | Hand and finger replantation after protracted ischemia (more than 24 hours) | Ann Plast Surg | 23 | Not addressed | Yes | Yes | No | 24–34 h total ischemia: 15/23 (65.2%) |
| Fufa et al 28 | 2013 | Digit replantation: experience of 2 US academic level-I trauma centers | J Bone Joint Surg Am | 67 | No significant association between ischemia time and replant survival | No | No | No | <6 h total ischemia: 22/43 (51.1%) 6–10 h total ischemia: 10/18 (55.6%) >10 h total ischemia: 3/6 (50.0%) |
| Mulders et al 29 | 2013 | Replantation and revascularization vs. amputation in injured digits | Hand (N Y) | 93 | Viable group significantly shorter mean total ischemia (4.6 vs 6.3) | No | No | No | 45/93 (48.4%) 4.6 h average total ischemia in viable group 6.3 h average total ischemia in necrosis group |
| Woo et al 30 | 2015 | Delayed and suspended replantation for complete amputation of digits and hands | J Hand Surg Am | 23 | No significant association between ischemia time and replant survival | Yes | Yes | Yes | Delayed, 9.4 h average total ischemia: 12/15 (80.0%) Suspended, 21.8 h average total ischemia: 7/8 (87.5%) Both groups’ survival rates similar to immediate replants performed concurrently. |
| Lima et al 31 | 2015 | Prognostic factors on survival rate of fingers replantation | Acta Ortop Bras | 50 | No significant association between ischemia time and replant survival | No | No | No | 27/50 (54%) 9.0 h average total ischemia in viable group 7.6 h average total ischemia in necrosis group |
| Breahna et al 32 | 2016 | Replantation of digits: a review of predictive factors for survival | J Hand Surg Eur Vol | 75 | Total ischemia time >6.5 h greater risk of necrosis than <6.5 h | No | No | No | 2.5–11.5 h warm ischemia: 52/75 (69.3%) |
| Zhu et al 4 | 2017 | Pre-operative predictive factors for the survival of replanted digits | Int Orthop | 291 | Warm ischemia time >12 h greater risk of necrosis than <6 h. Warm ischemia 6–12 h not different from <6 h or >12 h. | No | Temperature only | No | <6 h warm ischemia: 113/124 (91.1%) 6–12 h warm ischemia: 140/157 (89.2%) >12 h warm ischemia: 6/10 (60.0%) |
| Chen et al 33 | 2017 | Analysis of the factors affecting survival in digital replantation | Int J Clin Exp Med | 896 | Viable group significantly shorter mean total ischemia (8.1 ± 2.3 vs 9.9 ± 3.5) | No | No | No | 851/896 (95.0%) 8.1 ± 2.3 h average total ischemia in viable group 9.9 ± 3.5 h average total ischemia in necrosis group. |
| Wen et al 34 | 2017 | Fingertip replantation with palmar venous anastomoses in children | Ann Plast Surg | 21 | Not addressed | Yes | No | Yes | 5.5–18 h total ischemia: 20/21 (95.2%) |
| Cavadas et al 20 | 2018 | Immediate versus overnight-delayed digital replantation: comparative retrospective cohort study of survival outcomes | J Hand Surg Am | 597 | Replanted digit survival not significantly different in immediate and delayed approaches | No | No | No | Delayed replantation: 174/185 (94.1%) Immediate replantation: 375/412 (91.0%) |
| Kim et al 35 | 2018 | The concept of door-to-surgery time in distal digital replantation | J Korean Med Sci | 49 | Replanted digit survival not significantly different with <6 h or >6 h total injury-to-surgery time | No | No | No | <6 h total injury-to-surgery time: 21/26 (80.8%) >6 h total injury-to-surgery time: 17/23 (73.9%) |
| Jin et al 36 | 2019 | Pre-injury level of anxiety is associated with the rate of digit replant failure | Int J Surg | 134 | Warm ischemia time >12 h greater risk of necrosis than a <6 h. Warm ischemia 6–12 h not different from <6 h or >12 h. | No | Temperature only | No | <6 h warm ischemia: 49/54 (90.7%) 6–12 h warm ischemia: 70/76 (92.1%) >12 h warm ischemia: 2/4 (50%) |
Ten studies reported functional outcomes.
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,16
,19
,21
,22
,24
, 25
, 26
,30
,34
The criteria of Chen was the most common assessment, used in 3 studies.24
,25
,30
Others used a mix of several measures, including 2-point discrimination, range of motion, grip and pinch strength, palm-to-pulp distance, and skin wrinkling, pain, and cold intolerance. No study linked ischemia duration to functional outcomes. Waikakul et al25
concluded that a total ischemia time >9 hours was associated with 2-point discrimination >15 mm at a 2-year follow-up, but included subtotal amputations in these data, failed to report the preservation method, and conducted no multivariable analysis.Narrative Discussion of Meta-Analyses
In the setting of conflicting primary evidence, meta-analyses may help reach a conclusion. For ischemia times in digit replantation, the quality of these meta-analyses is low. In 2006, Dec
1
published a widely cited meta-analysis of factors affecting digit replantation success, claiming total ischemia times of any temperature >12 hours were associated with a greater chance of failure. This meta-analysis looked at just 2 studies with ischemia times: Tark et al21
and Waikakul et al.25
Tark et al’s21
1989 study reported an association between replant failure and a warm ischemia time >13 hours only. When including all replantation cases from Tark et al,21
success rates with <12 and >12 hours of ischemia were the same (80%), making Dec’s1
meta-analysis entirely dependent on the results from Waikakul et al25
(of note, the results from Tark et al21
in the Dec1
manuscript were not correctly transcribed, which we have reported to the journal where the paper appeared). It is difficult to draw transferrable conclusions from Waikakul et al.25
Although this study from Thailand reported that ischemia time does not significantly affect replant survival, the data were inadequate for several reasons. Of 1,018 digits, 273 (27%) were incomplete amputations and the results were not stratified based on this. Additionally, the preservation method was not reported, which may be especially important in Thailand, where the average temperature is around 30°C.Two subsequent meta-analyses were published in 2015 that both included 4 studies regarding ischemia time and replant survival.
37
,38
Two of these studies were unpublished master’s theses, and another looked at composite grafting without microvascular repair, not replantations. While this study concluded that ischemia times did not affect digit survival, we cannot draw meaningful conclusions regarding replantation. A 2018 meta-analysis found no association between ischemia time and replant survival, but only 2 studies were included: Fufa et al28
and Woo et al.30
,39
A 2019 meta-analysis compiled 117 digits from 28 papers to conclude that ischemia time did not significantly affect grip strength, 2-point discrimination, or Disabilities of the Arm, Shoulder, and Hand scores.40
The subset of papers and digits included in this analysis were not specified, but the data are likely influenced by the same weaknesses seen in the studies we reviewed. The literature lacks a large study with an assessment of long-term replantation outcomes clearly stratified by temperature and preservation method.Discussion
It remains unclear whether up to 24 hours of ischemia for a properly preserved digit significantly affects replant survival. These findings and the numerous reports of successful replantation well after 24 hours support the safety of delaying digital replantations with <6 hours of warm and <12 hours of cold ischemia time. Only 10 of the 22 studies we reviewed reported functional outcomes, and none were able to provide a robust analysis of the influence of ischemia time. Assessments were inconsistent, preventing comparisons across studies.
Numerous limitations were noted in several of the studies reporting that a longer ischemia time has an impact on replantation success, decreasing their applicability to current practice. While Arakaki and Tsai
23
found that a presurgery time >8 hours in sharp amputations conferred a greater risk of replant necrosis, operative times—which averaged 9.0 ± 5.9 hours—were not included in their analysis. Breahna et al32
noted that “in most cases the parts were not correctly preserved.” In the study from Zhu et al,4
only 10 of 291 digits had >12 hours of warm ischemia, and exact ischemia times were not provided. Jin et al36
had similar findings, but again had few digits with >12 hours of warm ischemia (4/134). Also, because most digits in this study were incorrectly preserved, those that were correctly preserved “in a saline-moistened gauze in an airtight bag on ice” were actually excluded from analysis, potentially biasing their results. Importantly, both Zhu et al4
and Jin et al26
found no difference in replanted digits with <6 and 6 to 12 hours of warm ischemia. Mulders et al29
and Chen et al33
both published studies showing shorter average ischemia times for successful replants but, again, the temperature and method of preservation were not recorded or used to stratify results.Despite conflicting reports associating long ischemia times with replantation failure, some have successfully implemented protocols that delay replantation when an emergent, overnight procedure can be avoided. Woo et al
30
demonstrated similar outcomes in digits that were replanted in a delayed or suspended fashion. Cavadas et al20
took this concept further and published a robust, 11-year experience with their protocol for replantation cases admitted after 6:00 pm with <6 hours of warm ischemia or <12 hours of cold ischemia that were routinely delayed until the next morning. They reported no difference in outcomes between acute and delayed replantation procedures.20
Emergency digit replantation is time and resource intensive. Overnight emergency surgery is disruptive, requires mobilization of on-call teams, and may be associated with replant failure.
32
It has also been associated with increased numbers of adverse events.41
, 42
, 43
Additionally, there is a concerning downward trend of digit replantation attempts in the United States, in what has been referred to as “the age of abandonment,” despite calls from the American Society for Surgery of the Hand, American College of Surgeons, and American College of Emergency Physicians to increase the frequency and availability of replantations.44
This threatens the availability of digit replantation for patients, as well as the number of hand surgeons able to perform the procedure. There is a large discrepancy in the reported success rates for replantation that is often attributed to, among other things, the volume of replantations being performed by the microsurgeon and the institution.28
,45
In 2012, a nationwide survey of trauma centers revealed that only 55% of level-I and 29% of level-II centers offered replantation procedures, and a 2018 study using the National Inpatient Sample database found that digit replantation attempts decreased from 8.4% in 2001 to 5.5% in 2014.45
,46
In a 2007 survey of American Society for Surgery of the Hand members, disruption of an elective schedule, time, inadequate support, and lifestyle incompatibility were cited as reasons for not participating in replantation and revascularization procedures.47
If a longer ischemia time with appropriate preservation is not detrimental to survival or functional outcomes of replantations, the management of digit amputations could change dramatically. Routine, less-expensive transfers could increase the catchment area for regional centers of excellence. Increased time for proper consultation and triage could obviate unnecessary, costly transfers. Alternatively, many surgeons working in replantation centers have called for greater delivery of replantation care at more trauma centers.
46
Protocol timing changes could allow for scheduling these cases the next day during normal working hours and could encourage greater participation by hand surgeons outside of large replantation referral centers, if desired. The policy implications of a revised approach to replantation timing are potentially broad, and either of the possibilities we discussed could result in increasing surgeon experience with the procedure and better availability for patients. However, better data on replantation timing and associated outcomes are needed to support potential policy changes.References
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- Eight cases of nine-digit and ten-digit replantations.Plast Reconstr Surg. 1996; 98: 477-484
- Five year digital replantation series from the frigid zone of China.Microsurgery. 1993; 14: 384-387
- Seven-digit replantation: digit survival after 39 hours of cold ischemia.Plast Reconstr Surg. 1986; 78: 522-525
- Three successful digital replantations in a patient after 84, 86, and 94 hours of cold ischemia time.Plast Reconstr Surg. 1988; 82: 346-350
- Replantation of amputated segments after prolonged ischemia.Plast Reconstr Surg. 1990; 85: 425-429
- Immediate versus overnight-delayed digital replantation: comparative retrospective cohort study of survival outcomes.J Hand Surg Am. 2018; 43: 625-630
- Replantation and revascularization of hands: clinical analysis and functional results of 261 cases.J Hand Surg Am. 1989; 14: 17-27
- Ten-digit and nine-digit replantation (4 cases).Br J Plast Surg. 1992; 45: 407-412
- Thumb replantation: survival factors and re-exploration in 122 cases.J Hand Surg Br. 1993; 18: 152-156
- The role of allopurinol in digital replantation.J Hand Surg Br. 1999; 24: 325-327
- Results of 1018 digital replantations in 552 patients.Injury. 2000; 31: 33-40
- Adjacent and spontaneous neurotization after distal digital replantation in children.Plast Reconstr Surg. 2003; 111 (discussion 166): 159-165
- Fingertip replantation: determinants of survival.Plast Reconstr Surg. 2008; 122: 833-839
- Digit replantation: experience of two US academic level-I trauma centers.J Bone Joint Surg Am. 2013; 95: 2127-2134
- Replantation and revascularization vs. amputation in injured digits.Hand (N Y). 2013; 8: 267-273
- Delayed and suspended replantation for complete amputation of digits and hands.J Hand Surg Am. 2015; 40: 883-889
- Prognostic factors on survival rate of fingers replantation.Acta Ortop Bras. 2015; 23: 16-18
- Replantation of digits: a review of predictive factors for survival.J Hand Surg Eur Vol. 2016; 41: 753-757
- Analysis of the factors affecting survival in digital replantation.Int J Clin Exp Med. 2017; 10: 5445-5448
- Fingertip replantation with palmar venous anastomoses in children.Ann Plast Surg. 2017; 78: 692-696
- The concept of door-to-surgery time in distal digital replantation.J Korean Med Sci. 2018; 33: e72
- Pre-injury level of anxiety is associated with the rate of digit replant failure: a prospective cohort study.Int J Surg. 2019; 69: 84-88
- Effects of non-surgical factors on digital replantation survival rate: a meta-analysis.J Hand Surg Eur Vol. 2016; 41: 157-163
- Nonsurgical factors of digital replantation and survival rate: a metaanalysis.Indian J Orthop. 2015; 49: 265-271
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- Predictors of hand function following digit replantation: quantitative review and meta-analysis.Hand (N Y). 2021; 16: 11-17
- Retrospective analysis of time of day of surgery and its 30 day in-hospital postoperative mortality rate at a single Canadian institution.Anesth Analg. 2016; 123: 764-765
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Article info
Publication history
Published online: August 07, 2021
Accepted:
July 2,
2021
Received:
September 23,
2020
Footnotes
No benefits in any form have been received or will be received related directly or indirectly to the subject of this article.
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© 2021 by the American Society for Surgery of the Hand. All rights reserved.
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