The Effect of Surgical Timing on Upper Extremity Nerve Repair

Abstract

Background:

The purpose of this study was to evaluate the association between timing of nerve repair and the ability to perform a primary nerve repair versus a bridge repair requiring the use of allograft, autograft, or a conduit in lacerated upper extremity peripheral nerve injuries.

Methods:

This is a retrospective case-control study of patients who underwent upper extremity nerve repair for lacerated peripheral nerves identified by Current Procedural Terminology codes. Timing of injury and surgery, as well as other information such as demographic information, mechanism of injury, site of injury, and type of nerve repair, was recorded. The odds of a patient requiring bridge repair based on the duration of time between injury and surgery was evaluated using logistic regression.

Results:

A total of 403 nerves in 335 patients (mean age 35.87 ± 15.33 years) were included. In all, 241 nerves were primarily repaired and 162 required bridge repair. Patients requiring bridge repair had a greater duration between injury and surgery compared with patients who underwent primary repair. Furthermore, the nerves requiring bridge repair were associated with a greater gap compared with the nerves repaired primarily. Based on logistic regression, each 1-day increase in duration between injury and surgery was associated with a 3% increase in the odds of requiring bridge repair.

Conclusions:

There is no defined critical window to achieve a primary nerve repair following injury. This study demonstrated that nerve injuries requiring bridge repair were associated with a significantly greater delay to surgery.

Introduction

The incidence of nerve injuries in patients presenting to a hospital or outpatient clinic with limb trauma is 1.64%. ¹ Epidemiologic studies have reported these injuries to occur more frequently in men (3:1), between 16 and 35 years of age, and most commonly due to domestic accidents caused by glass, knives, and so on. ² The most frequently injured nerves were the index finger radial digital nerve and small finger ulnar digital nerve. ²

The approach to surgical intervention for peripheral nerve injuries must consider many factors (mechanism of injury, location of injury, zone of injury, time since injury, associated bony, vascular, and soft tissue injuries, etc). Defining the nerve injury is of utmost importance, as each of these factors may dictate a different management strategy. Although the gold standard for the treatment of peripheral nerve lacerations is a tension-free primary repair, injury characteristics can often preclude this approach and necessitate a bridge repair with a conduit, nerve allograft, or nerve autograft.

Primary nerve repair for nerve lacerations is ideally performed in an acute setting to avoid nerve retraction, scar formation and adherence to surrounding tissues, and neuroma formation. In addition, neurotransmitters remain in the distal nerve ends within 72 hours of injury, allowing for intraoperative motor stimulation to enhance topographic alignment. ³ Many studies have reported the superior outcomes associated of early primary nerve repair compared with delayed repair and nerve grafting.^{4 -9} For this reason, an in-depth understanding of how nerve retraction, scar tissue adherence, and neuroma formation is affected by time from the injury will provide guidance on the optimization of modifiable factors (eg, timing of nerve repair) to allow primary nerve repair.

There is a lack of evidence characterizing how the time to nerve repair influences the type of repair that is achieved. Therefore, the aim of this study was to evaluate the association between timing of nerve repair and nerve retraction requiring the use of allograft, autograft, or a conduit. We hypothesized that increasing time of injury to nerve repair would result in higher utilization of a bridge repair.

Materials and Methods

This was a retrospective case-control study of patients who underwent upper extremity nerve repair at a large academic institution and its affiliated surgical centers between January 1, 2010 and December 31, 2020. Institutional review board approval was obtained. Patients were identified by Current Procedural Terminology (CPT) codes. Patient demographics and details of the initial injury, including date, mechanism (eg, sharp, crush, traction), and treatment, were recorded based on electronic medical records. Operative reports were reviewed to collect data, including the location of nerve injury, nerve characteristics, gap distance, and type of nerve repair performed. Patients with incomplete data, crush or traction mechanism of injury, revision surgery, and brachial plexus reconstruction were excluded. The primary outcome of this analysis was the difference in mean number of days from injury to surgery between nerves that were amenable to primary repair and nerves that required bridge repair. Secondary outcomes included: (1) the gap length between nerve ends; and (2) the odds of requiring bridge repair with increasing duration of time between injury and surgery.

Statistical Analysis

Sample size calculation for the primary outcome based on a medium effect size (d = 0.5) and α = .05 suggested that a total sample of 210 nerves would be sufficient to detect an effect with 95% power. Analysis was performed using R version 3.6.3 (The R Foundation for Statistical Computing, Vienna, Austria). Baseline characteristics were compared between the primary repair group and the bridge repair group. The difference between groups in number of days from injury to surgery and the difference in nerve gap distance were compared using unpaired t tests or Wilcoxon rank sum tests as appropriate. Logistic regression was used to evaluate the odds of a patient requiring bridge repair based on the length of time between injury and repair.

Results

A total of 403 nerves in 335 patients were included in the analysis. In all, 241 nerves in 206 patients were primarily repaired and 162 nerves in 129 patients required bridge repair. The overall mean age of the included patients was 35.87 ± 15.33 years with no difference in age between groups. Among all included patients, 43% were women with the bridge repair group demonstrating a higher proportion of men. Overall body mass index (BMI) was 26.00 ± 5.94 (Table 1).

Table 1.

Comparison of Demographic Characteristics Between Groups.

Characteristic	Primary repair, N = 206 a	Bridge repair, N = 129 a	P value b
Age, y	36.48 ± 15.09	34.89 ± 15.71	.3
Sex			.001
Female	102 (50%)	41 (32%)
Male	104 (50%)	88 (68%)
BMI	25.26 ± 5.38	27.03 ± 6.54	.022
Unknown	70	32
Smoking status			.13
Never	134 (71%)	80 (66%)
Former	34 (18%)	18 (15%)
Current	22 (12%)	24 (20%)
Unknown	16	7

Note. BMI = body mass index.

^aMean ± SD; No. (%).

^bWilcoxon rank sum test; Pearson χ² test.

Among all lacerated nerves, 55% of injuries occurred in the left upper extremity. The most common anatomic region was the digit, which accounted for 61% of the included nerves; 25% of nerve lacerations occurred in the hand, while nerves in the wrist, forearm, and elbow were less common injury locations. Most injuries occurred in sensory nerves (88% of the 403 included nerves), while pure motor nerves represented only 1.5% of the cohort (Table 2).

Table 2.

Comparison of Laterality, Anatomic Location, Nerve Function, Nerve Gap, and Duration Between Injury and Surgery Between Upper Extremity Nerves That Were Amenable to Primary Repair and Upper Extremity Nerves That Required Bridge Repair.

Characteristic	Primary repair, N = 241 a	Bridge repair, N = 162 a	P value b
Laterality			.033
Right	99 (41%)	84 (52%)
Left	142 (59%)	78 (48%)
Injury location			.047
Digit	152 (63%)	95 (59%)
Hand	58 (24%)	44 (27%)
Wrist	19 (7.9%)	6 (3.7%)
Forearm	6 (2.5%)	13 (8.0%)
Elbow	6 (2.5%)	4 (2.5%)
Nerve type			.2
Motor	5 (2.1%)	1 (0.6%)
Sensory	216 (90%)	140 (86%)
Mixed	20 (8.3%)	21 (13%)
Gap, mm	0.26 ± 1.58	15.66 ± 15.67	<.001
Time to surgery, d	14.12 ± 14.33	45.09 ± 62.85	<.001

^aMean ± SD; No. (%).

^bPearson χ² test; Fisher exact test; Wilcoxon rank sum test.

The mean gap between lacerated nerve ends was 0.26 ± 1.58 mm in the primary repair group and 15.66 ± 15.67 mm in the bridge repair group (95% confidence interval [CI]: [17.85, 12.97], P < .001). Among the nerves that were found to be amenable to primary repair, the mean length of time between injury and surgery was 14.12 ± 14.33 days. Among the nerves that were not amenable to primary repair and therefore required bridge repair, the mean length of time between injury and surgery was 45.09 ± 62.85 days (Figure 1). Overall, there was a mean difference of 30.96 days in the duration from injury to surgery between groups (95% CI: [40.88, 21.05], P < .001; Table 2, Figure 2). Based on logistic regression, each 1-day increase between injury and surgery was associated with a 3% increase in the odds of the injured upper extremity nerve requiring bridge repair (odds ratio = 1.03, 95% CI: [1.02, 1.05], P < .001; Figure 2).

Figure 1.

Distribution of the duration between injury and surgery for nerves that were amenable to primary repair and nerves that required bridge repair.

Figure 2.

Probability of requiring bridge repair following upper extremity nerve laceration based on the duration between injury and surgery.

Discussion

In our study, we found that peripheral nerve lacerations requiring bridge repair were associated with a greater delay from the time of injury to the time of surgery. In addition, the nerves requiring bridge repair were associated with a greater gap compared with the nerves repaired primarily. The specific cause of the nerve gap (zone of injury, resection of neuroma, fixed/retracted nerve, etc) was not elucidated in this retrospective study. However, based on logistic regression, each 1-day increase in duration between injury and surgery was associated with a 3% increase in the odds of requiring bridge repair.

In the current literature, there is a lack of an established guideline that defines the likelihood of being able to perform a primary nerve repair as it relates to time, that is, a critical window. There are several nonmodifiable factors that preclude acute primary repair. Complex trauma resulting in segmental nerve loss or a large zone of injury, lack of soft tissue coverage, and infection are examples. In these instances, resection of traumatized/nonviable tissue beyond the zone of injury is necessary and often results in a nerve gap that is not amenable to primary repair. In addition, the associated injuries may necessitate a subacute/delayed nerve repair also decreasing the odds of a primary repair.

In the setting where there are no contraindications to acute nerve repair, the primary modifiable factor to consider is timing of surgery. During the time between injury and surgery, there are a spectra of neural changes that may affect the ability to perform a primary repair. The elastin and collagen composition of the connective layers of peripheral nerves are of greatest abundance in the perineurium. ¹⁰ This layer is responsible for the tensile strength of the nerve as well as retraction in the setting of a complete nerve laceration. The elasticity of the nerve diminishes with time and can result in an inability to reapproximate the nerve ends at the time of repair. In addition, within the cascade of events following a complete nerve laceration is the inflammatory response, which results in fibroblast proliferation and the production of a dense fibrous scar that is adherent to perineural tissue. ¹¹ Last, when the distance between the lacerated nerve segments is too large for a prolonged period of time, axonal regrowth occurs in an unorganized manner resulting in a neuroma.^{12 -14} Oliveira et al performed a histologic animal study characterizing the morphologic stages of neuroma development following limb amputation. The authors found that signs of degenerating axons were present within 7 days and neuroma formation was evident between 7 and 28 days. ¹⁵ The authors concluded that neuroma prevention strategies would be more successful during the initial stages of development. Appropriately addressing a neuromatous nerve ending, which can begin to form as early as 1 to 2 weeks after injury, requires the nerve end to be trimmed beyond the neuroma, until healthy-appearing fascicles are visualized. The amount of nerve resected often results in a gap that is not amenable to primary repair. Each of these processes occurs simultaneously in a time-dependent manner, decreasing the likelihood to performing a primary repair. A more in-depth understanding of each of these factors will provide further guidance in determining the critical window of time to achieve a primary repair.

Our data suggest a similar timeline. Patients who underwent a primary repair underwent surgery at a mean of 2 weeks from the time of injury, whereas those who underwent a bridge repair underwent surgery at a mean of 6.5 weeks. In addition, we found that each 1-day increase in the duration between injury and surgery was associated with a 3% increase in the odds of requiring bridge repair. If this is extrapolated to a 1-month delay in surgery, approximately 90% of repairs will require a bridge repair.

The clinical implication of a well-defined critical window to pursue nerve repair is rooted in the body of literature that reports a superior outcome with primary repair compared with bridge repair.^{4 -9,16} Birch et al reported their long-term results following median and ulnar nerve repair comparing early primary repair, delayed primary repair, and delayed nerve grafting. The authors reported an earlier recovery and improved outcomes following primary repair. Ruijs et al conducted a meta-analysis seeking to quantify variables that influence the clinical outcome after median and ulnar nerve injuries. They reported on 23 studies and found that age, site of injury, and delay in surgery all had prognostic implications. The authors conclude that their results favor a primary repair. ⁸ Delay in surgery in this study is reported in monthly increments. Our study sought to further characterize the likelihood of being able to perform a primary repair in daily increments due to the understanding that the processes of nerve retraction, scar tissue formation/adherence, and neuroma formation are initiated from the time of injury and decrease the odds of primary repair with time. Kallio et al reported similar results in a series of 33 patients with radial nerve injuries. The authors found that operative delay was one of the crucial factors for regaining nerve function. ¹⁷ The importance of surgical timing and its implications regarding clinical outcomes have been similarly reported in multiple studies.^{7,18 -22} Although each of these series are heterogeneous, superior outcomes associated with primary repair, early intervention, and smaller nerve gaps is a theme that permeates through each study.

There are several limitations to our study. First, the retrospective design does not allow for standardization of nerve repair techniques and parameters. A lack of defining “tension-free” or acceptable limb positioning during nerve repair are 2 examples that can result in variability between surgeons. Second, we were not able to elucidate the status of the nerve ends to determine the reasoning for nerve trimming, that is, zone of injury, neuroma formation, perineural scar adherence, and so on. Third, our study did not correlate surgical parameters to clinical outcomes. Future prospective studies are needed to address these limitations and characterize clinical outcomes. Last, the sample size was too small to perform an adequate subgroup analysis comparing sensory, mixed motor sensory, and motor-only nerves to determine differences in timing of intervention and the ability to perform a primary repair. Similarly, this study is underpowered to evaluate the differences in gender and BMI. One hypothesis is that men may have presented in a more delayed fashion resulting in a higher likelihood of bridge repair. This can also account for the slight change in BMI between the groups. Larger-scale studies powered for secondary outcomes will allow for further elucidation of the importance of these findings.

In conclusion, this study found that nerve injuries requiring bridge repair were associated with a significantly greater delay from the time of injury to the time of surgery. The results of our study demonstrate that each 1-day increase in the duration between injury and surgery was associated with a 3% increase in the odds of requiring bridge repair. We therefore advocate for an expedited nerve repair in patients with nerve injuries amenable to acute intervention.