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Abstract

Introduction:

The efficacy of spinal anaesthesia with fentanyl supplementation for arthroscopic knee surgery remains controversial. We conducted a systematic review and meta-analysis to explore the influence of fentanyl supplementation for arthroscopic knee surgery.

Methods:

We searched PubMed, Embase, Web of Science, EBSCO and Cochrane Library databases through May 2019 for randomized controlled trials (RCTs) assessing the efficacy and safety of fentanyl supplementation for arthroscopic knee surgery. This meta-analysis is performed using the random-effects model.

Results:

Five RCTs are included in the meta-analysis. Overall, compared with the control group for knee arthroscopy, fentanyl supplementation is associated with decreased time for sensory block regression to S1 (mean difference (MD) = −47.38; 95% confidence interval (CI) = −56.74 to −38.02; p < 0.00001), first ambulation (MD = −41.65; 95% CI = −65.11 to −18.19; p = 0.0005), first urination (MD = −23.45; 95% CI = −32.16 to −14.74; p < 0.00001) and hospital discharge (MD = −29.39; 95% CI = −44.73 to −14.06; p = 0.0002) but has no substantial influence on onset time of anaesthesia (MD = 0.50; 95% CI = −1.71 to 2.70; p = 0.66), duration for motor blockade (MD = −42.56; 95% CI = −119.18 to 34.07; p = 0.28), pruritus (risk ratio (RR) = 2.17; 95% CI = 0.28 to 16.90; p = 0.46) or nausea (RR = 0.42; 95% CI = 0.10 to 1.81; p = 0.25).

Conclusions:

Fentanyl supplementation benefits postoperative recovery after knee arthroscopy.

Keywords

arthroscopic knee surgery fentanyl supplementation randomized controlled trials spinal anaesthesia

Introduction

In recent years, ambulatory cases and surgery have been increased for the purpose of reducing treatment expenses and hospitalization duration for economical and social needs.^1
–3 Spinal anaesthesia is widely used to create a sufficiently high blockage for the ambulatory surgery using local anaesthetics^4
–6 but is limited by a prolonged recovery in most ambulatory cases due to the blockade.^7,8 The reduction in the dose of local anaesthetics in combination with fentanyl has become an important approach to enhance the recovery after the ambulatory surgery.^9,10

For instance, low-dose bupivacaine is applied for day-case spinal anaesthesia and small doses of fentanyl are used to improve and prolong the analgesic effect.¹¹ The fentanyl adjunct (10–20 µg) is reported to have no obvious impact on the duration of motor block, but the high dose of fentanyl may lead to irritating pruritus.^12,13 Fentanyl supplementation is found to prolong the sensory block of bupivacaine and lidocaine, suggesting the potential of combining a smaller local anaesthetic dose with fentanyl for patients undergoing knee arthroscopy.^12,14

Current evidence is insufficient for routine clinical use of fentanyl supplementation for knee arthroscopy. Recently, several studies have investigated the efficacy and safety of fentanyl supplementation for arthroscopic knee surgery, but the results are conflicting.^7,15,16 This systematic review and meta-analysis of randomized controlled trials (RCTs) aim to assess the efficacy and safety of fentanyl supplementation in patients with arthroscopic knee surgery.

Materials and methods

This systematic review and meta-analysis are performed based on the guidance of the Preferred Reporting Items for Systematic Reviews and Meta-analysis statement and Cochrane Handbook for Systematic Reviews of Interventions.^17,18 No ethical approval and patient consent are required because all analyses are based on previously published studies.

Literature search and selection criteria

We systematically searched several databases including PubMed, Embase, Web of Science, EBSCO and the Cochrane Library from inception to May 2019 with the following keywords: fentanyl and arthroscopic knee surgery or knee arthroscopy. The reference lists of retrieved studies and relevant reviews are also hand-searched, and the process above is performed repeatedly to include additional eligible studies.

The inclusion criteria are presented as follows: (1) study design is RCT, (2) patients undergo arthroscopic knee surgery and (3) intervention treatments are fentanyl supplementation versus nothing.

Data extraction and outcome measures

Some baseline information is extracted from the original studies, and they include first author, number of patients, age, female, body mass index, surgical duration and detailed methods in two groups. Data are extracted independently by two investigators, and discrepancies are resolved by consensus. We have contacted the corresponding author to obtain the data when necessary.

The primary outcomes are sensory block regression to S1 and first ambulation. Secondary outcomes include first urination, onset time of anaesthesia, duration for motor blockade, hospital discharge, pruritus and nausea.

Quality assessment in individual studies

The methodological quality of each RCT is assessed by the Jadad scale, which consists of three evaluation elements: randomization (0–2 points), blinding (0–2 points), dropouts and withdrawals (0–1 points).¹⁹ One point would be allocated to each element if they have been conducted and mentioned appropriately in the original article. The score of the Jadad scale varies from 0 to 5 points. An article with Jadad score ≤2 is considered to be of low quality. The study is thought to be of high quality if Jadad score ≥3.²⁰

Statistical analysis

We assessed mean differences (MDs) with 95% confidence intervals (CIs) for continuous outcomes (sensory block regression to S1, first ambulation, first urination, onset time of anaesthesia, duration for motor blockade and hospital discharge) risk ratios (RRs) with 95% CIs for dichotomous outcomes (pruritus and nausea). Heterogeneity was evaluated using the I ² statistic, and I ² > 50% indicates significant heterogeneity.²¹ The random-effects model was used for all meta-analysis. We searched for potential sources of heterogeneity for significant heterogeneity. Sensitivity analysis was performed to detect the influence of a single study on the overall estimate via omitting one study in turn or performing the subgroup analysis. Owing to the limited number (<10) of the included studies, publication bias was not assessed. Results were considered as statistically significant for p < 0.05. All statistical analyses were performed using Review Manager Version 5.3 (The Cochrane Collaboration, Software Update, Oxford, UK).

Results

Literature search, study characteristics and quality assessment

Figure 1 shows a detailed flowchart of the search and selection results. Initially, 473 potentially relevant articles are identified. Finally, five RCTs are included in the meta-analysis.^{7,15,16,22,23}

Figure 1.

Flow diagram of study search and selection process.

The baseline characteristics of the five included RCTs are given in Table 1. These studies are published between 2005 and 2017, and the total sample size is 204. Among the included RCTs, fentanyl supplementation for spinal analgesia is regarded as the adjunctive therapy to articaine,¹⁵ mepivacaine,^16,22 bupivacaine⁷ and ropivacaine.²³

Table 1.

Characteristics of included studies.

No.	Author	Fentanyl group						Control group						Jada scores
No.	Author	Number	Age	Female (n)	BMI (kg/m²)	Surgical duration (min)	Methods	Number	Age	Female (n)	BMI (kg/m²)	Surgical duration (min)	Methods	Jada scores
1.	Stenman et al.¹⁵	30	46 ± 12	16	–	38 (15), median (IQR)	Articaine 60 mg with fentanyl 10 µg	29	47 ± 12	13	–	32 (20)	Plain articaine 60 mg with saline	5
2.	Kahn et al.¹⁶	10	46 (27–60), median (range)	2	28.5 ± 5.6	–	Mepivacaine 27 mg plus fentanyl 10 µg	22	41 (19–55)	12	26.3 ± 3.8	–	Mepivacaine 37.5 mg	4
3.	Unal et al.⁷	15	35.0 ± 12.4	11	26.1 ± 2.3	48.6 ± 17.5	4 mg 0.5% hyperbaric bupivacaine plus 25 mg of fentanyl	14	39.1 ± 6.9	9	26.2 ± 3.2	43.7 ± 18.0	4 mg 0.5% hyperbaric bupivacaine	3
4.	O’Donnell et al.²²	17	50.5 ± 15.9	8	30.2 ± 8.5	–	30 mg of isobaric mepivacaine 1.5% plus fentanyl 10 µg	17	42.7 ± 14.7	9	33.0 ± 8.7	–	45 mg of isobaric mepivacaine 1.5%	4
5.	Boztug et al.²³	25	39 ± 13	10	–	52 ± 22	8 mg isobaric ropivacaine plus 25 μg fentanyl	25	42 ± 14	7	–	65 ± 20	10 mg isobaric ropivacaine	4

BMI: body mass index; IQR: interquartile range.

Two studies report sensory block regression to S1,^16,22 three studies report first ambulation,^16,22,23 four studies report first urination,^15,16,22,23 two studies report onset time of anaesthesia,^22,23 two studies report duration for motor blockade,^15,23 two studies report hospital discharge^16,22 and two studies report pruritus and nausea.^15,16 Jadad scores of the five included studies vary from 3 to 5, and all five studies have high quality based on the quality assessment.

Primary outcomes: sensory block regression to S1 and first ambulation

The random-effects model is used for the analysis of primary outcome. The results find that compared to the control group for knee arthroscopy, fentanyl supplementation is associated with decreased time for sensory block regression to S1 (MD = −47.38; 95% CI = −56.74 to −38.02; p < 0.00001) with no heterogeneity among the studies (I ² = 0%, heterogeneity p = 0.80, Figure 2), and first ambulation (MD = −41.65; 95% CI = −65.11 to −18.19; p = 0.0005) with significant heterogeneity among the studies (I ² = 65%, heterogeneity p = 0.06, Figure 3).

Figure 2.

Forest plot for the meta-analysis of sensory block regression to S1.

Figure 3.

Forest plot for the meta-analysis of first ambulation.

Sensitivity analysis

No heterogeneity is observed for sensory block regression to S1, but there is significant heterogeneity for first ambulation. As shown in Figure 3, the study¹⁶ shows results that are completely out of range of the others and probably contributes to the heterogeneity. After excluding this study, the results suggest that fentanyl supplementation can substantially reduce the time for first ambulation after knee arthroscopy (MD = −27.60; 95% CI = −49.71 to −5.49; p = 0.01). No evidence of heterogeneity is observed among the remaining studies (I ² = 0%).

Secondary outcomes

In comparison with the control intervention for knee arthroscopy, fentanyl supplementation results in the decrease in first urination (MD = −23.45; 95% CI = −32.16 to −14.74; p < 0.00001; Figure 4) but has no notable impact on the onset time of anaesthesia (MD = 0.50; 95% CI = −1.71 to 2.70; p = 0.66; Figure 5) or on the duration for motor blockade (MD = −42.56; 95% CI = −119.18 to 34.07; p = 0.28; Figure 6). In addition, hospital discharge is found to be shorter in the fentanyl group than that in the control group (MD = −29.39; 95% CI = −44.73 to −14.06; p = 0.0002; Figure 7). There is no statistical difference of pruritus (RR = 2.17; 95% CI = 0.28 to 16.90; p = 0.46; Figure 8) or nausea (RR = 0.42; 95% CI = 0.10 to 1.81; p = 0.25; Figure 9) between the two groups.

Figure 4.

Forest plot for the meta-analysis of first urination.

Figure 5.

Forest plot for the meta-analysis of onset time of anaesthesia.

Figure 6.

Forest plot for the meta-analysis of duration for motor blockade.

Figure 7.

Forest plot for the meta-analysis of hospital discharge.

Figure 8.

Forest plot for the meta-analysis of pruritus.

Figure 9.

Forest plot for the meta-analysis of nausea.

Discussion

Several studies have revealed the advantage of adding fentanyl to other local anaesthetics for spinal anaesthesia.^24

–28 In an open inguinal herniorrhaphy, the addition of fentanyl 10 µg to hyperbaric articaine 72 mg for the spinal anaesthesia is reported to significantly reduce the need for supplemental intravenous fentanyl intraoperatively.²⁹ One included RCT involving knee arthroscopy, fentanyl 10 or 20 µg supplementation to articaine 60 mg for spinal anaesthesia can prolong the median duration of the sensory block at the T10 dermatomal level from 41 min to 69 min compared with articaine.¹⁵

Furthermore, the combination of 30 mg isobaric mepivacaine 1.5% with fentanyl 10 µg can generate reliable anaesthesia and a more rapid recovery for knee arthroscopy than 45 mg plain mepivacaine. The combination methods are associated with sensory block averaged 118 min and time to ambulation 176 min.^16,22 Our meta-analysis concludes that fentanyl supplementation is able to substantially reduce the time for sensory block regression to S1, first ambulation, first urination and hospital discharge after knee arthroscopy but shows no obvious impact on the onset time of anaesthesia or on the duration for motor blockade.

Regarding the sensitivity analysis, there is no evidence of heterogeneity after excluding the study,¹⁶ and the results find that fentanyl supplementation can decrease the time for first ambulation after knee arthroscopy. This heterogeneity may be caused by different doses and combination methods. One study reveals that mepivacaine–fentanyl combination may decrease the incidence of nausea and vomiting compared to mepivacaine for knee arthroscopy, which may be due to fewer requirements of opioids and mepivacaine.¹⁶ There is no significant difference of pruritus or nausea between the fentanyl group and the control group after knee arthroscopy based on the results of our meta-analysis.

Several limitations exist in this meta-analysis. Firstly, our analysis is based on only five RCTs, and more RCTs with a large sample size should be conducted to explore this issue. Next, there is significant heterogeneity, which may be caused by different combination and methods of adjuvant fentanyl. Finally, some unpublished and missing data may lead to some bias to the pooled effect.

Conclusion

Fentanyl supplementation promotes postoperative recovery after knee arthroscopy.

Footnotes

Declaration of conflicting interests

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The author(s) received no financial support for the research, authorship, and/or publication of this article.

ORCID iD

Jianfeng Chen

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