Sedation and analgesia practices at Italian neonatal intensive care units: results from the EUROPAIN study

Paola Lago, Anna Chiara Frigo, Eugenio Baraldi, Roberta Pozzato, Emilie Courtois, Jérôme Rambaud, Kanwaljeet J S Anand, Ricardo Carbajal, Paola Lago, Anna Chiara Frigo, Eugenio Baraldi, Roberta Pozzato, Emilie Courtois, Jérôme Rambaud, Kanwaljeet J S Anand, Ricardo Carbajal

Abstract

Background: We aimed to examine current bedside analgesia/sedation (A/S) and pain assessment (PA) practices in Italian neonatal intensive care units (NICUs) in relation to the findings of an epidemiological European study and recently-introduced national guidelines.

Methods: We analyzed the Italian data from the EUROPAIN (EUROpean-Pain-Audit-In-Neonates) prospective observational study on A/S practices that involved 6680 newborns admitted to tertiary-level NICUs in 18 European countries. Demographics, type of assisted ventilation, type and mode of A/S administration and PA were analyzed. Multivariate linear regression models were used to identify factors predicting A/S and PA practices.

Results: From October 1st, 2012 to June 30th, 2013, thirty Italian NICUs gathered data on 422 newborn: 131 on invasive ventilation (IV); 150 on noninvasive ventilation (NIV); and 141 on spontaneous ventilation (SV). A/S was documented for 35.3% of all infants admitted (86.3% IV; 17.3% NIV; 7.1% SV [p = 0.0001]), and varied considerably between NICUs (as reported in other European countries). Strong analgesics were used in 32.5% of cases, sedatives in 10.2%, mild analgesics in 3.8%. Fentanyl was used in 78.6% of cases, morphine in 8.4%, neuromuscular blockers in 5.3%, midazolam in 22.1%. The performance of PA was documented in 67.5% of all newborn (85.5% IV; 67.3% NIV; 51.1% SV [p = 0.001]). Illness severity, type of ventilation, bedside PA, and number of NICU beds were all factors associated with A/S use on multivariate analysis, while gestational age ≤ 32 weeks, and type of ventilation and presence of a pain team were associated with PA.

Conclusions: We documented a generally widespread, but still highly variable use of A/S and PA at Italian NICUs, despite the diffusion of national guidelines. There is an urgent need to improve routine PA to enable customized pain and stress control (and prevention) in all infants.

Trial registration: Clinical Trials.gov # NCT01694745 .

Keywords: Analgesic; Newborn and preterm; Opioids; Pain; Pain assessment; Sedative.

Figures

Fig. 1
Fig. 1
Study flowchart
Fig. 2
Fig. 2
Analgesia and sedation in Italy and in all participating countries in Europe by type of ventilation. EU include: Austria, Belgium, Cyprus, Estonia, Finland, France, Germany, Greece, Lithuania, Malta, Netherlands, Norway, Poland, Portugal, Spain, Sweden, United Kingdom. Chi-square test p < 0.001
Fig. 3
Fig. 3
Pain assessment in Italy and all participating countries in Europe. EU include: Austria, Belgium, Cyprus, Estonia, Finland, France, Germany, Greece, Lithuania, Malta, Netherlands, Norway, Poland, Portugal, Spain, Sweden, United Kingdom. ITA = pain assessment in Italian NICU admissions, PA_EU = pain assessment in other European NICU admissions, IV = pain assessment in invasive ventilation group, NIV = pain assessment in non-invasive ventilation group, SR = pain assessment in spontaneous ventilation group. Chi-square test p < 0.001

References

    1. Anand KJS, Hickey PR. Pain and its effects in the human neonate and fetus. N Engl J Med. 1987;317:1321–9. doi: 10.1056/NEJM198711193172105.
    1. Anand KJ, Hickey PR. Halothane-morphine compared with high-dose sufentanil for anesthesia and postoperative analgesia in neonatal cardiac surgery. N Engl J Med. 1992;326:1–9. doi: 10.1056/NEJM199201023260101.
    1. Carbajal R, Rousset A, Danan C, Coquery S, et al. Epidemiology and treatment of painful procedures in neonates in intensive care units. JAMA. 2008;300:60–70. doi: 10.1001/jama.300.1.60.
    1. Taddio A, Katz J, Ilersich AL, Koren G. Effect of neonatal circumcision on pain response during subsequent routine vaccination. Lancet. 1997;349:599–603. doi: 10.1016/S0140-6736(96)10316-0.
    1. Vinall J, Miller SP, Bjornson BH, Fitzpatrick KP, et al. Invasive procedures in preterm children: brain and cognitive development at school age. Pediatrics. 2014;133:412–21. doi: 10.1542/peds.2013-1863.
    1. Grunau RE, Whitfield MF, Petrie-Thomas J, Synnes AR, et al. Neonatal pain, parenting stress and interaction, in relation to cognitive and motor development at 8 and 18 months in preterm infants. Pain. 2009;143:138–46. doi: 10.1016/j.pain.2009.02.014.
    1. Anand KJ, Palmer FB, Papanicolaou AC. Repetitive neonatal pain and neurocognitive abilities in ex-preterm children. Pain. 2013;154:1899–901. doi: 10.1016/j.pain.2013.06.027.
    1. Zwicker JG, Grunau RE, Adams E, Chau V, et al. Score for neonatal acute physiology-II and neonatal pain predict corticospinal tract development in premature newborns. Pediatr Neurol. 2013;48:123–9. doi: 10.1016/j.pediatrneurol.2012.10.016.
    1. Anand KJ, Hall RW, Desai N, Shephard B, et al. NEOPAIN Trial Investigators Group. Effects of morphine analgesia in ventilated preterm neonates: primary outcomes from the NEOPAIN randomised trial. Lancet. 2004;363:1673–82. doi: 10.1016/S0140-6736(04)16251-X.
    1. Davidson A, Flick RP. Neurodevelopmental implications of the use of sedation and analgesia in neonates. Clin Perinatol. 2013;40:559–73. doi: 10.1016/j.clp.2013.05.009.
    1. Dong C, Anand KJ. Developmental neurotoxicity of ketamine in pediatric clinical use. Toxicol lett. 2013;220:53–60. doi: 10.1016/j.toxlet.2013.03.030.
    1. Ancora G, Lago P, Garetti E, Pirelli A, et al. Efficacy and safety of continuous infusion of fentanyl for pain control in preterm newborn on mechanical ventilation (MV) J Pediatr. 2013;163(3):645–651. doi: 10.1016/j.jpeds.2013.02.039.
    1. Ferguson SA, Ward WL, Paule MG, Hall RW, Annad KJ. A pilot study of preemptive morphine analgesia in preterm neonates: effects on head circumference, social behavior, and response latencies in early childhood. Neurotoxicol Teratol. 2012;34(1):47–55. doi: 10.1016/j.ntt.2011.10.008.
    1. de Graaf J, van Lingen RA, Simons SH, Anand KJ, et al. Long-term effects of routine morphine infusion in mechanically ventilated neonates on children's functioning: five-year follow-up of a randomized controlled trial. Pain. 2011;152(6):1391–7. doi: 10.1016/j.pain.2011.02.017.
    1. Anand KJS, International Evidence-Based Group for neonatal pain Consensus statement for the prevention and management of pain in the newborn. Arch Pediatr Adolesc Med. 2001;155:173–80. doi: 10.1001/archpedi.155.2.173.
    1. Lago P, Merazzi D, Garetti E, Pieragostini L, et al. Guidelines for procedural pain in the newborn. Acta Pediatrica. 2009;98:932–939. doi: 10.1111/j.1651-2227.2009.01291.x.
    1. American Academy of Pediatrics, Committee on fetus and newborn and section on anesthesiology and pain medicine Prevention and management of procedural pain in the neonate: an update. Pediatrics. 2016;137(2):e20154271. doi: 10.1542/peds.2015-4271.
    1. Lago P, Guadagni A, Merazzi D, Ancora G, et al. Pain management in the neonatal intensive care unit: a national survey in Italy. Paediatr Anaesth. 2005;15:925–31. doi: 10.1111/j.1460-9592.2005.01688.x.
    1. Lago P, Boccuzzo G, Garetti E, Pirelli, et al. Pain management during invasive procedures at Italian NICUs: has anything changed in the last five years? J Matern Fetal Neonatal Med. 2012;25:148–50. doi: 10.3109/14767058.2012.725973.
    1. Lago P, Garetti E, Ancora G, Merazzi D, for the Pain Study Group of the Italian Society of Neonatology et al. Procedural pain in neonates: the state of the art in the implementation of national guidelines in Italy. Pediatr Anesth. 2013;23(5):407–414. doi: 10.1111/pan.12107.
    1. Carbajal R, Eriksson M, Courtois E, Boyle E, et al. Sedation and analgesia practices in neonatal intensive care units (EUROPAIN): results from a prospective cohort study. Lancet Respir Med. 2015;3(10):796–812. doi: 10.1016/S2213-2600(15)00331-8.
    1. Lund GC, Green D, Browne R, Ackerman N. New CRIB Score: one score for all NICU admissions. Pediatr Res. 1997;41:162. doi: 10.1203/00006450-199704001-00976.
    1. Schmidt B, Adelmann C, Stutzer H, et al. Comparison of sufentanil versus fentanyl in ventilated term neonates. Klin Padiatr. 2010;222:62–6. doi: 10.1055/s-0029-1225348.
    1. Ng E, Taddio A, Ohlsson A. Intravenous midazolam infusion for sedation of infants in the neonatal intensive care unit. Cochrane Database Syst Rev. 2012;6
    1. Koch SC, Fitzgerald M, Hathway GJ. Midazolam potentiates nociceptive behavior, sensitizes cutaneous reflexes, and is devoid of sedative action in neonatal rats. Anesthesiology. 2008;108:122–9. doi: 10.1097/01.anes.0000296079.45446.15.
    1. Lago P, Garetti E, Pirelli A, Merazzi D, et al. Linee Guida per la prevenzione ed il trattamento del dolore nel neonato. Edizioni Biomedia giugno. 2016.
    1. Demsey EM, Hazzani Al F, Faucher D, Barrington KJ. Facilitation endotracheal intubation with mivacurium and fentanyl in the neonatal intensive care unit. Arch Dis Child Fetal Neonatal Ed. 2006;91:F279–282. doi: 10.1136/adc.2005.087213.
    1. Lemyre B, Cheng R, Gaboury I. Atropine, fentanyl and succinylcholine for non-urgent intubations in newborns. Arch Dis Child Fetal Neonatal Ed. 2009;94(6):F439–442. doi: 10.1136/adc.2008.146068.
    1. Alexander SM, Todres ID. The use of sedation and muscle relaxation in the ventilated infants. Clin Perinatol. 1998;25(1):63–78.
    1. Rozisky JR, Laste G, de Macedo IC, Santos VS, et al. Neonatal morphine administration leads to changes in hippocampal BDNF levels and antioxidant anzyme activity in the adult life rats. Neurochem Res. 2013;38(3):494–503. doi: 10.1007/s11064-012-0941-8.
    1. De Graaf J, Van Lingen RA, Valkenburg AJ, Weisglas-Kuperus N, et al. Does neonatal morphine use affect neuropsychological outcomes at 8 to 9 years of age? Pain. 2013;154:449–58. doi: 10.1016/j.pain.2012.12.006.
    1. Zwicker JG, Miller SP, Grunau RE, Chau V, et al. Smaller cerebellar growth and poorer neurodevelopmental outcomes in very preterm infants exposed to neonatal morphine. J Pediatr. 2016;172:81–87. doi: 10.1016/j.jpeds.2015.12.024.
    1. Deindl P, Giordano V, Fuiko R, Waldhoer T, Unterasinger L, Berger A, et al. The implementation of systematic pain and sedation management has no impact on outcome in extremely preterm infants. Acta Paediatr. 2016;105:798–805. doi: 10.1111/apa.13334.
    1. Dyke MP, Kohan R, Evans S. Morphine increases synchronous ventilation in preterm infants. J Paediatr Child Health. 1995;31:176–9. doi: 10.1111/j.1440-1754.1995.tb00780.x.
    1. Grunau RE. Neonatal pain in very preterm infants: long-term effects on brain, neurodevelopment and pain reactivity. Rambam Maimonides Med J. 2013;4
    1. Bellù R, de Waal WK, Zanini R. Opioids for neonates receiving mechanical ventilation. Cochrane Database Syst Rev. 2008;23(1)
    1. Taylor BJ, Robbins JM, Gold JI, Logsdon TR, Bird TM, Anand KJS. Assessing postoperative pain in neonates: a multicenter observational study. Pediatrics. 2006;118:e992–1000. doi: 10.1542/peds.2005-3203.
    1. Bhandari V, Bergqvist LL, Kronsberg SS, Barton BA, Anand KJ. Morphine administration and short-term pulmonary outcomes among ventilated preterm infants. Pediatrics. 2005;116:352–9. doi: 10.1542/peds.2004-2123.

Source: PubMed

Sponzoři a spolupracovníci

Zdravotní podmínky

Drogové intervence

3
Předplatit