Skip to main content

Advertisement

Log in

Postoperative pain in the neonate: age-related differences in morphine requirements and metabolism

  • Neonatal and Pediatric Intensive Care
  • Published:
Intensive Care Medicine Aims and scope Submit manuscript

Abstract

Objective

To investigate age-related differences in morphine requirements and metabolism in full-term neonates.

Design and setting

Randomized double-blind study in the pediatric surgical intensive care unit.

Patients

Sixty-eight neonates (52 aged under 7 days, 16 aged 7 day or older) following major surgery.

Interventions

After surgery patients were randomly assigned to continuous morphine (10 µg/kg per hour) or intermittent morphine (30 µg/kg per 3 hours). Additional morphine was administered on guidance of pain scores.

Measurements and results

Pain was measured by the Comfort behavioral scale and visual analogue scale. Morphine and morphine-6-glucuronide (M6G) plasma concentrations were determined before and 0, 6, 12, and 24 h after surgery. The younger neonates differed significantly from the older neonates in morphine requirement (median 10 vs. 10.8 µg/kg per hour), morphine plasma concentration [23.0 vs. 15.3 ng/ml), and M6G/morphine ratio (0.6 vs. 1.5). Pain scores did not differ between age groups or morphine treatment groups. Neonates who were mechanically ventilated longer than 24 h had significantly higher morphine plasma concentrations than the spontaneously breathing neonates 12 and 24 h after surgery (29.1 vs. 13.1 ng/ml and 26.9 vs. 12.0 ng/ml, respectively). Morphine plasma concentrations were not correlated with analgesia or respiratory depression. Five neonates (intermittent morphine) showed respiratory insufficiency; however, the difference between the groups was not significant.

Conclusions

Neonates aged 7 days or younger require significantly less morphine postoperatively than older neonates. The two morphine regimens (continuous, intermittent) were equally effective and safe. Mechanical ventilation decreases morphine metabolism and clearance.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1.

Similar content being viewed by others

References

  1. Choonara I (1999) Why do babies cry. BMJ 319:1381

    CAS  PubMed  Google Scholar 

  2. Lima de J, Lloyd-Thomas AR, Howars RF, Sumner E, Quinn TM (1996) Infant and neonatal pain anaesthetists' perceptions and prescribing patterns. BMJ 313:787

    PubMed  Google Scholar 

  3. Anand KJS (2001) Consensus statement for the prevention and management of pain in the newborn. Arch Pediatr Adolesc Med 155:173–180

    CAS  PubMed  Google Scholar 

  4. Anand KJS, Sippell WG, Aynsley-Green A (1987) Randomized trial of fentanyl anesthesia in preterm babies undergoing surgery: effects on the stress response. Lancet I:243–248

    Google Scholar 

  5. Fitzgerald M, Millard C, McIntosh N (1989) Cutaneous hypersensitivity following peripheral tissue damage in newborn infants and its reversal with topical anesthesia. Pain 39:31–36

    Article  CAS  PubMed  Google Scholar 

  6. Anand KJS, Scalzo FM (2000) Can adverse neonatal experiences alter brain development and subsequent behavior? Biol Neonate 77:69–82

    Google Scholar 

  7. Lynn AM, Slattery JT (1987) Morphine pharmacokinetics in early infancy. Anesthesiology 66:136–139

    CAS  PubMed  Google Scholar 

  8. Choonara IA, McKay P, Hain R, Rane A (1989) Morphine metabolism in children. Br J Clin Pharmacol 28:599–604

    CAS  PubMed  Google Scholar 

  9. McRorie TI, Lynn AM, Nespeca MK, Opheim KE, Slattery JT (1992) The maturation of morphine clearance and metabolism. Am J Dis Child 146:972–976

    CAS  PubMed  Google Scholar 

  10. Pokela ML, Olkkola KT, Seppälä T, Koivisto M (1993) Age-related morphine kinetics in infants. Dev Pharmacol Ther 20:26–34

    CAS  PubMed  Google Scholar 

  11. Faura CC, Collins SL, Moore RA, McQuay HJ (1998) Systematic review of factors affecting the ratios of morphine and its major metabolites. Pain 74:43–53

    Article  CAS  PubMed  Google Scholar 

  12. Bouwmeester NJ, Anand KJS, Dijk van M, Hop WCJ, Boomsma F, Tibboel D (2001) Hormonal and metabolic stress responses after major surgery in children aged 0–3 years: a double-blind, randomized trial comparing the effects of continuous versus intermittent morphine. Br J Anaesth 87:390–399

    Article  CAS  PubMed  Google Scholar 

  13. Bouwmeester NJ, van den Anker JN, Hop WCJ, Anand KJS, Tibboel D (2003) Age- and therapy-related effects on morphine requirements and plasma concentrations of morphine and its metabolites in postoperative infants. Br J Anaesth 90:642–652

    Google Scholar 

  14. Anand KJS, Aynsley-Green A (1988) Measuring the severity of surgical stress in newborn infants. J Pediatr Surg 23:297–305

    CAS  PubMed  Google Scholar 

  15. Ambuel B, HamLett KW, Marx CM, Blumer JL (1992) Assessing distress in paediatric intensive care environments: the Comfort scale. J Pediatr Psychol 17:95–109

    CAS  PubMed  Google Scholar 

  16. Dijk van M, Boer de JB, Koot HM, Tibboel D, Passchier J, Duivenvoorden HJ (2000) The reliability and validity of the COMFORT scale as a postoperative pain instrument in 0–3 year-old infants. Pain 84:367–377

    Article  PubMed  Google Scholar 

  17. Lynn AM, Nespeca MK, Opheim KE, Slattery JT (1993) Respiratory effects of intravenous morphine infusions in neonates, infants, and children after cardiac surgery. Anesth Analg 77:695–701

    CAS  PubMed  Google Scholar 

  18. Verwey-van Wissen CP, Koopman-Kimenai PM, Vree TB (1991) Direct determination of codeine, norcodeine, morphine and normorphine with their corresponding O-glucuronide conjugates by high-performance liquid chromatography with electrochemical detection. J Chromatogr 570:309–320

    PubMed  Google Scholar 

  19. Kart T, Christrup LL, Rasmussen M (1997) Recommended use of morphine in neonates, infants and children based on a literature review. II. Clinical use. Pediatr Anaesth 7:93–101

    CAS  Google Scholar 

  20. Lynn AM, Nespeca MK, Bratton SL, Strauss SG, Shen DD (1998) Clearance of morphine in postoperative infants during intravenous infusions: the influence of age and surgery. Anesth Analg 86:958–963

    CAS  PubMed  Google Scholar 

  21. Lynn AM, Nespeca MK, Bratton SL, Shen DD (2000) Intravenous morphine in postoperative infants: intermittent dosing versus targeted continuous infusions. Pain 88:89–95

    Article  CAS  PubMed  Google Scholar 

  22. Richard C, Berdeaux A, Delion F, Riou B, Rimailho A, Giudicelli JF, Auzepy P (1986) Effect of mechanical ventilation on hepatic drug pharmacokinetics. Chest 90:837–841

    CAS  PubMed  Google Scholar 

  23. Mutlu GM, Mutlu EA, Factor P (2001) GI Complications in patients receiving mechanical ventilation. Chest 119:1222–1241

    Article  CAS  PubMed  Google Scholar 

  24. Coffman B, Rios GR, King CD, Tephly TR (1997) Human UGT2B7 catalyzes morphine glucuronidation. Drug Metab Dispos 25:1–4

    CAS  PubMed  Google Scholar 

  25. Dijk M van, Boer de JB, Koot HM, Duivenvoorden HJ, Passchier J, Bouwmeester N, Tibboel D (2001) The association between physiological and behavioral pain measures in 0- to 3-year old infants after major surgery. J Pain Symptom Manage 22:600–609

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

The laboratory assistance of Dr. P.M. Koopman-Kiemenai, Department of Clinical Pharmacy, University Hospital Nijmegen, is gratefully acknowledged. We also thank the pharmacists, the anesthetists, surgeons, anesthetic nurses, intensivists, and pediatric ICU nurses of the Sophia Children's Hospital for their co-operation, Mrs. L. Visser-Isles and Mr. K. Hagoort (Erasmus Medical Center, Rotterdam) for the editing, and, finally, the parents and their children, who allowed this study to take place.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Nancy J. Bouwmeester.

Additional information

The study was supported by The Netherlands Research Council (NWO, The Hague) and the Sophia Foundation for Medical Research.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Bouwmeester, N.J., Hop, W.C.J., van Dijk, M. et al. Postoperative pain in the neonate: age-related differences in morphine requirements and metabolism. Intensive Care Med 29, 2009–2015 (2003). https://doi.org/10.1007/s00134-003-1899-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00134-003-1899-4

Keywords

Navigation