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Meta-Analysis
. 2018 Mar 2;3(3):CD010368.
doi: 10.1002/14651858.CD010368.pub2.

Use of hyaluronidase as an adjunct to local anaesthetic eye blocks to reduce intraoperative pain in adults

Heinrich Rüschen  1 , Kavitha Aravinth, Catey Bunce, Desta Bokre
Affiliations
Meta-Analysis

Use of hyaluronidase as an adjunct to local anaesthetic eye blocks to reduce intraoperative pain in adults

Heinrich Rüschen et al. Cochrane Database Syst Rev. .

Abstract

Background: Hyaluronidase has been used over many decades as an adjunct to local anaesthetic solution to improve the speed of onset of eye blocks and to provide better akinesia and analgesia. With the evolution of modern eye surgery techniques, fast onset and akinesia are not essential requirements anymore. The assumption that the addition of hyaluronidase to local anaesthetic injections confers better analgesia for the patient needs to be examined. There has been no recent systematic review to provide evidence that hyaluronidase actually improves analgesia.

Objectives: To ascertain if adding hyaluronidase to local anaesthetic solutions for use in ophthalmic anaesthesia in adults results in a reduction of perceived pain during the operation and to assess harms, participant and surgical satisfaction, and economic impact.

Search methods: We carried out systematic searches in Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, and four other databases in June 2017. We searched the trial registers at www.ISRCTN.com, ClinicalTrials.gov and www.clinicaltrialsregister.eu for relevant trials. We imposed no language restrictions.

Selection criteria: We included randomized controlled trials (RCTs) that evaluated the effect of hyaluronidase on pain experienced by adults during intraocular surgery using a rating scale.

Data collection and analysis: Two review authors (HR and KA) independently extracted data and assessed methodological quality using standard procedures as expected by Cochrane.

Main results: We included seven trials involving 500 participants that studied the effect of hyaluronidase on intraoperative pain. Four of the seven trials with 289 participants reported the primary outcome in a dichotomous manner, and we proceeded to meta-analyse the findings which showed a moderate heterogeneity that could not be explained (I2 = 41% ). The pooled risk ratio (RR) for these four trials was 0.83 with the 95% confidence interval ranging from 0.48 to 1.42. The reduction in intraoperative pain scores in the hyaluronidase group were not statistically significant. Among the three trials that reported the primary outcome in a continuous manner, the presence of missing data made it difficult to conduct a meta-analysis. To further explore the data, we imputed standard deviations for the other studies from another included RCT (Sedghipour 2012). However, this resulted in substantial heterogeneity between study estimates (I² = 76% ). The lack of reported relevant data in two of the three remaining trials made it difficult to assess the direction of effect in a clinical setting.Overall, there was no statistical difference regarding the intraoperative reduction of pain scores between the hyaluronidase and control group. All seven included trials had a low risk of bias.According to GRADE, we found the quality of evidence was low and downgraded the trials for serious risk of inconsistency and imprecision. Therefore, the results should be analysed with caution.Participant satisfaction scores were significantly higher in the hyaluronidase group in two high quality trials with 122 participants. Surgical satisfaction was also superior in two of three high quality trials involving 141 participants. According to GRADE, the quality of evidence was moderate for participant and surgical satisfaction as the trials were downgraded for imprecision due to the small sample sizes. The risk of bias in these trials was low.There was no reported harm due to the addition of hyaluronidase in any of the studies. No study reported on the cost of hyaluronidase in the context of eye surgery.

Authors' conclusions: The effects of adding hyaluronidase to local anaesthetic fluid on pain outcomes in people undergoing eye surgery are uncertain due to the low quality of evidence available. A well designed RCT is required to address inconsistency and imprecision among the studies and to determine the benefit of hyaluronidase to improve analgesia during eye surgery. Participant and surgical satisfaction is higher with hyaluronidase compared to the control groups, as demonstrated in moderate quality studies. There was no harm attributed to the use of hyaluronidase in any of the studies. Considering that harm was only rarely defined as an outcome measure, and the overall small number of participants, conclusions cannot be drawn about the incidence of harmful effects of hyaluronidase. None of the studies undertook cost calculations with regards to use of hyaluronidase in local anaesthetic eye blocks.

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Conflict of interest statement

HR: no known conflict of interest.

KA: no known conflict of interest.

CB : no known conflict of interest.

DB : no known conflict of interest.

Figures

1
1
Study flow diagram.
2
2
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
3
3
Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
4
4
Forest plot of comparison: 1 Hyaluronidase versus control, outcome: 1.1 Intraoperative pain (measured by analogue rating scales; reported continuous).
5
5
Forest plot of comparison: 1 Hyaluronidase versus control, outcome: 1.2 Intraoperative pain (measured by analogue rating scales; reported dichotomous).
1.1
1.1. Analysis
Comparison 1 Hyaluronidase versus control, Outcome 1 Intraoperative pain (reported continuous).
1.2
1.2. Analysis
Comparison 1 Hyaluronidase versus control, Outcome 2 Intraoperative pain (reported dichotomous).
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References

References to studies included in this review

Bowman 1997 {published data only (unpublished sought but not used)}
    1. Bowman RJ, Newman DK, Richardson EC, Callear AB, Flanagan DW. Is hyaluronidase helpful for peribulbar anaesthesia?. Eye 1997;11(Pt 3):385‐8. [PUBMED: 9373482] - PubMed
Brydon 1995 {published data only (unpublished sought but not used)}
    1. Brydon CW, Basler M, Kerr WJ. An evaluation of two concentrations of hyaluronidase for supplementation of peribulbar anaesthesia. Anaesthesia 1995;50(11):998‐1000. [PUBMED: 8678264] - PubMed
Khandwala 2008 {published data only (unpublished sought but not used)}
    1. Khandwala M, Ahmed S, Goel S, Simmons IG, McLure HA. The effect of hyaluronidase on ultrasound‐measured dispersal of local anaesthetic following sub‐Tenon injection. Eye 2008;22(8):1065‐8. [PUBMED: 17525774] - PubMed
Remy 2008 {published data only (unpublished sought but not used)}
    1. Remy M, Pinter F, Nentwich MM, Kampik A, Schönfeld CL. Efficacy and safety of hyaluronidase 75 IU as an adjuvant to mepivacaine for retrobulbar anesthesia in cataract surgery. Journal of Cataract and Refractive Surgery 2008;34(11):1966‐9. [PUBMED: 19006746] - PubMed
Rowley 2000 {published data only (unpublished sought but not used)}
    1. Rowley SA, Hale JE, Finlay RD. Sub‐Tenon's local anaesthesia: the effect of hyaluronidase. British Journal of Ophthalmology 2000;84(4):435‐6. [PUBMED: 10729306] - PMC - PubMed
Sedghipour 2012 {published data only (unpublished sought but not used)}
    1. Sedghipour M, Mahdawifard A, Fouladi RF, Gharabaghi D, Rahbani M, Amiraslanzadeh G, et al. Hyaluronidase in subTenon's anaesthesia for phacoemulsification, a double blind randomized clinical trial. International Journal of Ophthalmology 2012;5(3):389‐92. [PUBMED: 22773994] - PMC - PubMed
Shiroma 2002 {published data only (unpublished sought but not used)}
    1. Shiroma HF, Ferreira EM, Isaac DLC, Ghanem VC, Arieta CEL. A comparison of 1% ropivacaine efficacy when associated or not with hyaluronidase in peribulbar anaesthesia in cataract surgery [Comparação da eficácia da ropivacaína 1% quando associada ou não à hialuronidase na anestesia peribulbar para cirurgia de catarata]. Arquivos Brasileiros de Oftalmologia 2002;65(5):525‐8. [0004‐2749; lil‐322156]

References to studies excluded from this review

Berg 2001 {published data only (unpublished sought but not used)}
    1. Berg AA, Montoya‐Pelaez LF. Comparison of lignocaine 2% with adrenaline, bupivacaine 0.5% with or without hyaluronidase and a mixture of bupivacaine, lignocaine and hyaluronidase for peribulbar block analgesia. Acta Anaesthesiologica Scandinavica 2001;45(8):961‐6. [PUBMED: 11576046] - PubMed
Crawford 1994 {published data only (unpublished sought but not used)}
    1. Crawford M, Kerr WJ. The effect of hyaluronidase on peribulbar block. Anaesthesia 1994;49(10):907‐8. [PUBMED: 7802194] - PubMed
Guise 1999 {published and unpublished data}
    1. Guise P, Laurent S. Sub‐Tenon's block: the effect of hyaluronidase on speed of onset and block quality. Anaesthesia and Intensive Care 1999;27(2):179‐81. [PUBMED: 10212716] - PubMed
House 1991 {published data only (unpublished sought but not used)}
    1. House PH, Hollands RH, Schulzer M. Choice of anesthetic agents for peribulbar anesthesia. Journal of Cataract and Refractive Surgery 1991;17(1):80‐3. [PUBMED: 2005563] - PubMed
Johansen 1993 {published data only (unpublished sought but not used)}
    1. Johansen J, Kjeldgård M, Corydon L. Retrobulbar anaesthesia: a clinical evaluation of four different anaesthetic mixtures. Acta Ophthalmologica 1993;71(6):787‐90. [PUBMED: 8154254] - PubMed
Lange 1989 {published data only (unpublished sought but not used)}
    1. Lange W, Denffer H, Honis M. Comparison of bupivacaine 0.75% with a mixture of bupivacaine 0.75% and mepivacaine 2% in retrobulbar anaesthesia: effects of hyaluronidase. Fortschritte der Ophthalmologie 1989;86(4):312‐5. [PUBMED: 2676792] - PubMed
Moharib 2002 {published data only (unpublished sought but not used)}
    1. Moharib MM, Mitra S, Rizvi SG. Effect of alkalinization and/or hyaluronidase adjuvancy on a local anesthetic mixture for sub‐Tenon's ophthalmic block. Acta Anaesthesiologica Scandinavica 2002;46(5):599‐602. [PUBMED: 12027856] - PubMed
Morsman 1992 {published data only (unpublished sought but not used)}
    1. Morsman CD, Holden R. The effects of adrenaline, hyaluronidase and age on peribulbar anaesthesia. Eye 1992;6(3):290‐2. [PUBMED: 1446762] - PubMed
Ramanathan 1999 {published data only (unpublished sought but not used)}
    1. Ramanathan US, Sullivan CA, Thompson SM, McCauley D. A study of effect of hyaluronidase on subTenon anaesthesia. Cataract Surgery and Assessment 1999;40(4):S287.
Sarvela 1992 {published data only (unpublished sought but not used)}
    1. Sarvela J, Nikki P. Hyaluronidase improves regional ophthalmic anaesthesia with etidocaine. Canadian Journal of Anaesthesia 1992;39(9):920‐4. [PUBMED: 1451220] - PubMed
Soares 2002 {published data only (unpublished sought but not used)}
    1. Soares LF, Escovedo Helayel P, Conceição DB, Oliveira Filho GR. Peribulbar block with the association of 0.5% enantiomeric mixture of bupivacaine and 2% lignocaine: effects of hyaluronidase addition. Revista Brasileira de Anestesiologia 2002;52(4):420‐5. [PUBMED: 19479106] - PubMed

Additional references

Afshari 2017
    1. Afshari A, Wetterslev J, Smith AF. Can systematic reviews with sparse data be trusted?. Anaesthesia 2017;72(1):12‐6. [PUBMED: 27804113 ] - PubMed
Alhassan 2015
    1. Alhassan MB, Kyari F, Ejere HOD. Peribulbar versus retrobulbar anaesthesia for cataract surgery. Cochrane Database of Systematic Reviews 2015, Issue 7. [DOI: 10.1002/14651858.CD004083.pub3] - DOI - PMC - PubMed
Atkinson 1949
    1. Atkinson WS. Use of hyaluronidase with local anaesthesia in ophthalmology; preliminary report. Archives of Ophthalmology 1949;42(5):628‐33. [PUBMED: 15393388 ] - PubMed
Borders 1968
    1. Borders CL, Raferty MA. Purification and partial characterization of testicular hyaluronidase. Journal of Biological Chemistry 1968;243(13):3756‐62. [PUBMED: 5658550] - PubMed
Brown 1999
    1. Brown S, Brooks S, Mazow M, Avilla C, Braverman D, Greenhaw S, et al. Cluster of diplopia cases after periocular anesthesia without hyaluronidase. Journal of Cataract and Refractive Surgery 1999;25(9):1245‐9. [PUBMED: 10476509 ] - PubMed
Brown 2001
    1. Brown S, Coats D, Collins M, Underdahl J. Second cluster of strabismus cases after periocular anesthesia without hyaluronidase. Journal of Cataract and Refractive Surgery 2001;27(11):1872‐5. [PUBMED: 11709263] - PubMed
Buhren 2016
    1. Buhren BA, Schrumpf H, Hoff NP, Bölke N, Hilton S, Gerber PA. Hyaluronidase: from clinical applications to molecular and cellular mechanisms. European Journal of Medical Research 2016;21(5). [PUBMED: 26873038] - PMC - PubMed
Dempsey 1997
    1. Dempsey GA, Barrett PJ, Kirby IJ. Hyaluronidase and peribulbar block. British Journal of Anaesthesia 1997;78(6):671‐4. [PUBMED: 9215017] - PubMed
GRADEpro GDT [Computer program]
    1. McMaster University (developed by Evidence Prime). GRADEpro GDT. Version accessed August 2017. Hamilton (ON): McMaster University (developed by Evidence Prime), 2015.
Guay 2015
    1. Guay J, Sales K. Sub‐Tenon's anaesthesia versus topical anaesthesia for cataract surgery. Cochrane Database of Systematic Reviews 2015, Issue 8. [DOI: 10.1002/14651858.CD006291.pub3] - DOI - PMC - PubMed
Guyatt 2011
    1. Guyatt G, Oxman AD, Akl EA, Kunz R, Vist G, Brozek J, et al. GRADE guidelines: 1. Introduction ‐ GRADE evidence profiles and summary of findings tables. Journal of Clinical Epidemiology 2011;64(4):383‐94. [PUBMED: 21195583 ] - PubMed
Higgins 2011
    1. Higgins JPT, Green S, editor(s). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 (updated March 2011). The Cochrane Collaboration, 2011. Available from handbook.cochrane.org.
Hylenex® Prescribing Information 2016
    1. Halozyme Therapeutics, Inc. Hylenex® recombinant prescribing information, 2016. hylenex.com/downloads/approved‐uspi‐lbl301feb2016.pdf (accessed 27 January 2018).
Kempeneers 1992
    1. Kempeneers A, Dralands L, Ceuppens J. Hyaluronidase induced orbital pseudotumour as complication of retrobulbar anesthesia. Bulletin de la Societe Belge d'Ophtalmologie 1992;243:159‐66. [PUBMED: 1302146 ] - PubMed
Koornneef 1988
    1. Koornneef L. Eyelid and orbital fascial attachments and their clinical significance. Eye 1988;2(2):130‐4. [PUBMED: 3197870] - PubMed
Meyer 1934
    1. Meyer K, Palmer FW. The polysaccharide of the vitreous humour. Journal of Biochemistry 1934;107:629‐34.
RevMan 2014 [Computer program]
    1. The Nordic Cochrane Centre, The Cochrane Collaboration. Review Manager (RevMan). Version 5.3. Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration, 2014.
Roberts 1993
    1. Roberts J, MacLeod B, Hollands RH. Improved peribulbar anaesthesia with alkalinization and hyaluronidase. Canadian Journal of Anaesthesia 1993;40(9):835‐8. [PUBMED: 8403178] - PubMed
Schein 2000
    1. Schein OD, Friedman DS, Fleisher LA, Lubomski LH, Magaziner J, Sprintz M, et al. Anaesthesia Management During Cataract Surgery. Evidence Report/Technology Assessment Number 16 AHRQ Publication No. 00‐E015 (Archived). Vol. 1, Rockville (MD): Agency for Healthcare Research and Quality, 2001.
WHO 2010
    1. World Health Organization. WHO guidelines on tissue infectivity distribution in transmissible spongiform encephalopathies, 2010. www.who.int/bloodproducts/tse/WHO%20TSE%20Guidelines%20FINAL‐22%20Juneup... (accessed 27 January 2018).

References to other published versions of this review

Rüschen 2013
    1. Rüschen H, Adams L, Bunce C. Use of hyaluronidase as an adjunct to local anaesthetic eye blocks. Cochrane Database of Systematic Reviews 2013, Issue 2. [DOI: 10.1002/14651858.CD010368] - DOI - PMC - PubMed

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