Clonidine for pain in non-ventilated infants
- PMID: 32270873
- PMCID: PMC7143321
- DOI: 10.1002/14651858.CD013104.pub2
Clonidine for pain in non-ventilated infants
Abstract
Background: Critically ill newborn infants undergo a variety of painful procedures or experience a variety of painful conditions during their early life in the neonatal unit. In the critically ill paediatric and neonatal population, clonidine is prescribed as an adjunct to opioids or benzodiazepines aiming to reduce the doses of these drugs that are required for analgesia or sedation, or to facilitate weaning from mechanical ventilation. It has been shown that clonidine premedication might have a positive effect on postoperative pain in children.
Objectives: To assess the benefit and harms of clonidine for the prevention or treatment of procedural pain; postoperative pain; or pain associated with clinical conditions in non-ventilated neonates.
Search methods: We used the standard search strategy of Cochrane Neonatal to search the CENTRAL, MEDLINE via PubMed, Embase, and CINAHL to December 2018. We also searched clinical trials databases, conference proceedings, and the reference lists of retrieved articles for randomised controlled trials and quasi-randomised trials. We ran an updated search from 1 January 2018 to 11 March 2020 in CENTRAL via CRS Web, MEDLINE via Ovid, and CINAHL via EBSCOhost.
Selection criteria: Randomised controlled trials, quasi-randomised controlled trials, and cluster trials comparing clonidine to placebo or no treatment, opioids, paracetamol, dexmedetomidine, or non-pharmacological pain-reducing interventions for the management of procedural pain, postoperative pain, and pain associated with clinical conditions in preterm and term newborns.
Data collection and analysis: Two review authors independently planned to extract data (e.g. number of participants, birth weight, gestational age, modality of administration, and dose of clonidine) and assess the risk of bias (e.g. adequacy of randomisation, blinding, completeness of follow-up). The primary outcome considered was pain: for procedural pain, the mean values of each analgesia scale assessed during the procedure and at one to two hours after the procedure; for postoperative pain and for pain associated with clinical conditions, the mean values of each analgesia scale assessed at 30 minutes, three hours, and 12 hours after the administration of the intervention. We planned to use the GRADE approach to assess the quality of evidence.
Main results: Our search strategy yielded 3383 references. Two review authors independently assessed all references for inclusion. We did not find any completed studies for inclusion. We excluded three trials where clonidine was administered for spinal anaesthesia.
Authors' conclusions: We did not find any studies that met our inclusion criteria and hence there is no evidence to recommend or refute the use of clonidine for the prevention or treatment of procedural or postoperative pain, or pain associated with clinical conditions in neonates.
Copyright © 2020 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Conflict of interest statement
OR: none.
MC: none.
EN: none.
MB: none.
Update of
References
References to studies excluded from this review
Batra 2010 {published data only}
Delous 2010 {published data only}
-
- Delous E, Rochette A, Bringuier S, Dadure C, Capdevila X. Spinal anaesthesia with clonidine: duration & tolerance: a prospective, randomized, double‐blinded study in 111 neonates. (preliminary results). Regional Anaesthesia and Pain Medicine 2010;35(5):E53‐4. [DOI: 10.1097/AAP.0b013e3181f3582c] - DOI
Rochette 2004 {published data only}
-
- Rochette A, Raux O, Troncin R, Dadure C, Verdier R, Capdevila X. Clonidine prolongs spinal anaesthesia in newborns: a prospective dose‐ranging study. Anaesthesia and Analgesia 2004;98(1):56‐9. [PUBMED: 14693584] - PubMed
References to studies awaiting assessment
Rochette 1998 {published data only}
-
- Rochette A, Raux O, Borry J, Vergnes C, d'Athis F. Clonidine prolongs bupivacaine spinal anaesthesia in newborns. British Journal of Anaesthesia 1998;80 (Suppl 1):141.
References to ongoing studies
NCT01075490 {unpublished data only}
-
- NCT01075490. Neonatal spinal anesthesia: effects of the addition of clonidine. clinicaltrials.gov/show/NCT01075490 (first received 25 February 2010).
Additional references
Allegaert 2007
Anand 1987a
Anand 1987b
-
- Anand KJ, Sippell WG, Aynsley‐Green A. Randomised trial of fentanyl anaesthesia in preterm babies undergoing surgery: effects on the stress response. Lancet 1987;1(8524):62‐6. [PUBMED: 2879174] - PubMed
Anand 2004
-
- Anand KJ, Hall RW, Desai N, Shephard B, Bergqvist LL, Young TE, et al. NEOPAIN Trial Investigators Group. Effects of morphine analgesia in ventilated preterm neonates: primary outcomes from the NEOPAIN randomised trial. Lancet 2004;363(9422):1673‐82. [DOI: 10.1016/S0140-6736(04)16251-X; PUBMED: 15158628] - DOI - PubMed
Ansermino 2003
-
- Ansermino M, Basu R, Vandebeek C, Montgomery C. Nonopioid additives to local anaesthetics for caudal blockade in children: a systematic review. Paediatric Anaesthesia 2003;13(7):561‐73. [PUBMED: 12950855] - PubMed
Barker 1995
Bauer 2013
Bayley 1993
-
- Bayley N. Bayley Scales of Infant Development. 2nd Edition. San Antonio (TX): Psychological Corporation, 1993.
Bayley 2006
-
- Bayley N. Bayley Scales of Infant and Toddler Development. 3rd Edition. San Antonio (TX): Harcourt Assessment, 2006.
Bellieni 2005
-
- Bellieni CV, Bagnoli F, Sisto R, Neri L, Cordelli D, Buonocore G. Development and validation of the ABC pain scale for healthy full‐term babies. Acta Paediatrica 2005;94(10):1432‐6. [PUBMED: 16299876] - PubMed
Benis 2001
-
- Benis MM, Suresh GK. Frequency of invasive procedures in very low birth weight (VLBW) infants in the neonatal intensive care unit (NICU). Pediatric Research 2001; Vol. 49, issue 4:392A.
Brummelte 2012
Bueno 2013
Butt 2013
Capino 2016
Carbajal 1997
-
- Carbajal R, Paupe A, Hoenn E, Lenclen R, Olivier‐Martin M. APN: evaluation behavioral scale of acute pain in newborn infants. Archives de Pediatrie 1997;4(7):623‐8. [PUBMED: 9295899] - PubMed
Carbajal 2008
-
- Carbajal R, Rousset A, Danan C, Coquery S, Nolent P, Ducrocq S, et al. Epidemiology and treatment of painful procedures in neonates in intensive care units. JAMA 2008;300(1):60‐70. [PUBMED: 18594041] - PubMed
Ceelie 2013
-
- Ceelie I, Wildt SN, Dijk M, Berg MM, Bosch GE, Duivenvoorden HJ, et al. Effect of intravenous paracetamol on postoperative morphine requirements in neonates and infants undergoing major noncardiac surgery: a randomized controlled trial. JAMA 2013;309(2):149‐54. [DOI: 10.1001/jama.2012.148050; PUBMED: 23299606] - DOI - PubMed
Chana 2001
Chen 2015
Cochrane EPOC 2017
-
- Cochrane Effective Practice, Organisation of Care (EPOC). EPOC resources for review authors, 2017. Available at epoc.cochrane.org/epoc‐resources‐review‐authors (accessed prior to 25 March 2020).
Costa 2013
Cravero 2011
de Graaf 2013
Debillon 2001
Duffett 2012
Egger 1997
Fitzgerald 1986
-
- Fitzgerald M, Koltzenburg M. The functional development of descending inhibitory pathways in the dorsolateral funiculus of the newborn rat spinal cord. Brain Research 1986;389(1‐2):261‐70. [PUBMED: 3948011] - PubMed
Gibbins 2014
Golianu 2007
GRADEpro GDT [Computer program]
-
- Grade Working Group, McMaster University. GRADEpro GDT. Version accessed 10 August 2017. Hamilton (ON): Grade Working Group, McMaster University, 2015.
Gregoretti 2009
-
- Gregoretti C, Moglia B, Pelosi P, Navalesi P. Clonidine in perioperative medicine and intensive care unit: more than an anti‐hypertensive drug. Current Drug Targets 2009;10(8):799‐814. [PUBMED: 19702526] - PubMed
Griffiths 1954
-
- Griffiths R. The Abilities of Babies: a Study in Mental Measurement. New York (NY): McGraw‐Hill Book Co. Inc, 1954.
Grunau 1998
-
- Grunau RE, Oberlander T, Holsti L, Whitfield MF. Bedside application of the Neonatal Facial Coding System in pain assessment of premature neonates. Pain 1998;76(3):277‐86. [PUBMED: 9718246] - PubMed
Hammer 1989
-
- Hammer RP Jr, Ricalde AA, Seatriz JV. Effects of opiates on brain development. Neurotoxicology 1989;10(3):475‐83. [PUBMED: 2696899] - PubMed
Handelmann 1985
-
- Handelmann GE, Dow‐Edwards D. Modulation of brain development by morphine: effects on central motor systems and behavior. Peptides 1985;6 Suppl 2:29‐34. [PUBMED: 4080616] - PubMed
Higgins 2003
Higgins 2011
-
- Higgins JP, 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.
Higgins 2019
-
- Higgins JP, Thomas J, Chandler J, Cumpston M, Li T, Page MJ, Welch VA, editor(s). Cochrane Handbook for Systematic Reviews of Interventions version 6.0 (updated July 2019). Cochrane, 2019. Available from www.training.cochrane.org/handbook. - PMC - PubMed
Hodgkinson 1994
-
- Hodgkinson K, Bear M, Thorn J, Blaricum S. Measuring pain in neonates: evaluating an instrument and developing a common language. Australian Journal of Advanced Nursing 1994;12(1):17‐22. [PUBMED: 7786451] - PubMed
Holsti 2008
Hoy 2011
Hummel 2008
Hummel 2010
Hünseler 2014
-
- Hünseler C, Balling G, Röhlig C, Blickheuser R, Trieschmann U, Lieser U, et al. Clonidine Study Group. Continuous infusion of clonidine in ventilated newborns and infants: a randomized controlled trial. Pediatric Critical Care Medicine 2014;15(6):511‐22. [DOI: 10.1097/PCC.0000000000000151; PUBMED: 24751788 ] - DOI - PubMed
ICROP 1984
-
- Committee for the Classification of Retinopathy of Prematurity. An international classification of retinopathy of prematurity. Pediatrics 1984;74(1):127‐33. [PUBMED: 6547526] - PubMed
Jacobs 2013
Jamadarkhana 2010
Jobe 2001
Johnston 1997
-
- Johnston CC, Collinge JM, Henderson SJ, Anand KJ. A cross‐sectional survey of pain and pharmacological analgesia in Canadian neonatal intensive care units. Clinical Journal of Pain 1997;13(4):308‐12. [PUBMED: 9430811] - PubMed
Krechel 1995
-
- Krechel SW, Bildner J. CRIES: a new neonatal postoperative pain measurement score. Initial testing of validity and reliability. Paediatric Anaesthesia 1995;5(1):53‐61. [PUBMED: 8521311] - PubMed
Lambert 2014
Laudenbach 2002
-
- Laudenbach V, Mantz J, Lagercrantz H, Desmonts JM, Evrard P, Gressens P. Effects of alpha(2)‐adrenoceptor agonists on perinatal excitotoxic brain injury: comparison of clonidine and dexmedetomidine. Anesthesiology 2002;96(1):134‐41. [PUBMED: 11753013] - PubMed
Lawrence 1993
-
- Lawrence J, Alcock D, McGrath P, Kay J, MacMurray SB, Dulberg C. The development of a tool to assess neonatal pain. Neonatal Network 1993;12(6):59‐66. [PUBMED: 8413140] - PubMed
Lim 2017
-
- Lim Y, Godambe S. Prevention and management of procedural pain in the neonate: an update, American Academy of Pediatrics, 2016. Archives of Disease in Childhood. Education and Practice Edition 2017;102(5):254‐6. [PUBMED: 28724533] - PubMed
Lundqvist 2014
Ma 2007
Mantz 2011
McPherson 2007
McPherson 2012
Milesi 2010
-
- Milesi C, Cambonie G, Jacquot A, Barbotte E, Mesnage R, Masson F, et al. Validation of a neonatal pain scale adapted to the new practices in caring for preterm newborns. Archives of Disease in Childhood. Fetal and Neonatal Edition 2010;95(4):F263‐6. [DOI: 10.1136/adc.2008.144758; PUBMED: 19221401] - DOI - PubMed
Nishina 1999
-
- Nishina K, Akamatsu H, Mikawa K, Shiga M, Maekawa N, Obara H, et al. The effects of clonidine and dexmedetomidine on human neutrophil functions. Anesthesia and Analgesia 1999;88(2):424‐8. [PUBMED: 9972773] - PubMed
Ohlsson 2016
Papile 1978
-
- Papile LA, Burstein J, Burstein R, Koffler H. Incidence and evolution of subependymal and intraventricular hemorrhage: a study of infants with birth weights less than 1,500 gm. Journal of Pediatrics 1978;92(4):529‐34. [PUBMED: 305471] - PubMed
Paris 2006
Peters 2003
-
- Peters JW, Koot HM, Grunau RE, Boer J, Druenen MJ, Tibboel D, et al. Neonatal Facial Coding System for assessing postoperative pain in infants: item reduction is valid and feasible. Clinical Journal of Pain 2003;19(6):353‐63. [PUBMED: 14600535] - PubMed
Pichot 2012
Pillai Riddell 2015
Pontén 2012
Review Manager 2014 [Computer program]
-
- Nordic Cochrane Centre, The Cochrane Collaboration. Review Manager 5 (RevMan 5). Version 5.3. Copenhagen: Nordic Cochrane Centre, The Cochrane Collaboration, 2014.
Ricalde 1990
-
- Ricalde AA, Hammer RP Jr. Perinatal opiate treatment delays growth of cortical dendrites. Neuroscience Letters 1990;115(2‐3):137‐43. [PUBMED: 2172870] - PubMed
Rochette 2005
-
- Rochette A, Troncin R, Raux O, Dadure C, Lubrano JF, Barbotte E, et al. Clonidine added to bupivacaine in neonatal spinal anesthesia: a prospective comparison in 124 preterm and term infants. Paediatric Anaesthesia 2005;15(12):1072‐7. [DOI: 10.1111/j.1460-9592.2005.01664.x; PUBMED: 16324026] - DOI - PubMed
Romantsik 2017
Roze 2008
-
- Roze JC, Denizot S, Carbajal R, Ancel PY, Kaminski M, Arnaud C, et al. Prolonged sedation and/or analgesia and 5‐year neurodevelopment outcome in very preterm infants: results from the EPIPAGE cohort. Archives of Pediatrics & Adolescent Medicine 2008;162(8):728‐33. [DOI: 10.1001/archpedi.162.8.728; PUBMED: 18678804] - DOI - PubMed
Schünemann 2013
-
- Schünemann H, Brożek J, Guyatt G, Oxman A, editors. GRADE Working Group. Handbook for grading the quality of evidence and the strength of recommendations using the GRADE approach (updated October 2013). GRADE Working Group, 2013. Available from gdt.gradepro.org/app/handbook/handbook.html.
Seatriz 1993
-
- Seatriz JV, Hammer RP Jr. Effects of opiates on neuronal development in the rat cerebral cortex. Brain Research Bulletin 1993;30(5‐6):523‐7. [PUBMED: 8384517] - PubMed
Shah 2012
Simons 2003
Spence 2005
Stevens 1996
-
- Stevens B, Johnston C, Petryshen P, Taddio A. Premature Infant Pain Profile: development and initial validation. Clinical Journal of Pain 1996;12(1):13‐22. [PUBMED: 8722730] - PubMed
Stevens 2016
Taddio 2009
Taniguchi 2004
-
- Taniguchi T, Kidani Y, Kanakura H, Takemoto Y, Yamamoto K. Effects of dexmedetomidine on mortality rate and inflammatory responses to endotoxin‐induced shock in rats. Critical Care Medicine 2004;32(6):1322‐6. [PUBMED: 15187514] - PubMed
Taniguchi 2008
Tesoro 2005
van Dijk 2009
Viberg 2014
-
- Viberg H, Eriksson P, Gordh T, Fredriksson A. Paracetamol (acetaminophen) administration during neonatal brain development affects cognitive function and alters its analgesic and anxiolytic response in adult male mice. Toxicological Sciences 2014;138(1):139‐47. [DOI: 10.1093/toxsci/kft329; PUBMED: 24361869] - DOI - PubMed
Walker 2012
Walsh 2004
-
- Walsh MC, Yao Q, Gettner P, Hale E, Collins M, Hensman A, et al. National Institute of Child Health and Human Development Neonatal Research Network. Impact of a physiologic definition on bronchopulmonary dysplasia rates. Pediatrics 2004;114(5):1305‐11. [DOI: 10.1542/peds.2004-0204; PUBMED: 15520112] - DOI - PubMed
References to other published versions of this review
Romantsik 2018
-
- Romantsik O, Calevo MG, Norman E, Bruschettini M. Clonidine for painful procedures or conditions in infants. Cochrane Database of Systematic Reviews 2018, Issue 8. [DOI: 10.1002/14651858.CD013104] - DOI
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