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Common Errors of Drug Administration in Infants

Causes and Avoidance

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Abstract

Drug administration errors are common in infants. Although the infant population has a high exposure to drugs, there are few data concerning pharmacokinetics or pharmacodynamics, or the influence of paediatric diseases on these processes. Children remain therapeutic orphans. Formulations are often suitable only for adults; in addition, the lack of maturation of drug elimination processes, alteration of body composition and influence of size render the calculation of drug doses complex in infants.

The commonest drug administration error in infants is one of dose, and the commonest hospital site for this error is the intensive care unit. Drug errors are a consequence of system error, and preventive strategies are possible through system analysis. The goal of a zero drug error rate should be aggressively sought, with systems in place that aim to eliminate the effects of inevitable human error. This involves review of the entire system from drug manufacture to drug administration. The nuclear industry, telecommunications and air traffic control services all practise error reduction policies with zero error as a clear goal, not by finding fault in the individual, but by identifying faults in the system and building into that system mechanisms for picking up faults before they occur. Such policies could be adapted to medicine using interventions both specific (the production of formulations which are for children only and clearly labelled, regular audit by pharmacists, legible prescriptions, standardised dose tables) and general (paediatric drug trials, education programmes, nonpunitive error reporting) to reduce the number of errors made in giving medication to infants.

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References

  1. Manasse HR. Toward defining and applying a higher standard of quality for medication use in the United States. Am J Hosp Pharm 1995; 52: 374–9

    Google Scholar 

  2. Pepper GA. Errors in drug administration by nurses. Am J Hosp Pharm 1995; 52: 390–5

    CAS  Google Scholar 

  3. Kelly W. Pharmacy contributions to adverse medication events. Am J Hosp Pharm 1995; 52: 385–90

    CAS  Google Scholar 

  4. Bordun LA, Butt W. Drug errors in intensive care. J Paediatr Child Health 1992; 28: 309–11

    Article  PubMed  CAS  Google Scholar 

  5. Leape LL. Preventing adverse drug events. Am J Hosp Pharm 1995; 52: 379–82

    CAS  Google Scholar 

  6. Barker KN, Allan EL. Research on drug-use-system errors. Am J Hosp Pharm 1995; 52: 400–4

    CAS  Google Scholar 

  7. Leape LL, Brennan TA, Laird N, et al. The nature of adverse events in hospitalized patients: results of the Harvard Medical Practice Study II. N Engl J Med 1991; 324(6): 377–84

    Article  PubMed  CAS  Google Scholar 

  8. Jonville AP, Autret E, Bavoux F, et al. Characteristics of medication errors in paediatrics. DICP Drug Intell Clin Pharm 1991; 25: 1113–7

    CAS  Google Scholar 

  9. Gupta A, Walhauser LK. Adverse drug reactions from birth to early childhood. Pediatr Clin North Am 1997; 44(1): 79–88

    Article  PubMed  CAS  Google Scholar 

  10. Soumerai SB, Ross-Degnan D. Drug prescribing in pediatrics: challenges for quality improvement. Pediatrics 1990; 86(5): 782–4

    PubMed  CAS  Google Scholar 

  11. Fosarelli P, Wilson M, DeAngelis C. Prescription medications in infancy and early childhood. Am J Dis Child 1987; 41: 772–5

    Google Scholar 

  12. Gross F. International workshop on perinatal and pediatric aspects of clinical pharmacology. Eur J Clin Pharmacol 1980; 18: 1–2

    Article  Google Scholar 

  13. Lesko SM, Epstein MF, Mitchell AA. Recent patterns of drug use in newborn intensive care. Pediatr Pharmacol Ther 1990; 116(6): 985–90

    CAS  Google Scholar 

  14. Curran WI, Beecher HK. Experimentation in children: a re-examination of legal and ethical principles. JAMA 1969; 10: 77–83

    Article  Google Scholar 

  15. Shirkey H. Therapeutic orphans [editorial]. J Pediatr 1968; 72: 119–20

    Article  PubMed  CAS  Google Scholar 

  16. Meakin G. Role of propofol in paediatric anaesthetic practice. Paediatr Anaesth 1995; 5: 147–9

    Article  PubMed  CAS  Google Scholar 

  17. Taussig HB. A study of the German outbreak of phocomelia: the thalidomide syndrome. JAMA 1962; 180: 1106–14

    Article  PubMed  CAS  Google Scholar 

  18. Burns LE, Hodgman JE, Cass AB. Fatal circulatory collapse in premature infants receiving chloramphenicol. N Engl J Med 1959; 261: 1318

    Article  PubMed  CAS  Google Scholar 

  19. Kula K. Dental problems. In: Oski FA, DeAngeles CD, McMillan JA, et al., editors. Principles and practice of paediatrics. 2nd ed. Philadelphia: J.B. Lippincott Company, 1994: 864

    Google Scholar 

  20. Whitington PF, Gartner LM. Disorders of bilirubin metabolism. In: Nathan DG, Oski FA, editors. Hematology of infancy and childhood. 4th ed. Philadelphia: W.B. Saunders Company, 1993: 92

    Google Scholar 

  21. Kauffman RE. Fentanyl, fads and folly: who will adopt the therapeutic orphans? J Pediatr 1991; 119: 588–9

    Article  PubMed  CAS  Google Scholar 

  22. McCloskey JJ, Haun SE, Deshpande JK. Bupivacaine toxicity secondary to continuous caudal epidural infusion in paediatric patients. Anesth Analg 1992; 75: 287–90

    Article  PubMed  CAS  Google Scholar 

  23. Agarwal R, Gutlove DP, Lockhart CH. Seizures occurring in pediatric patients receiving continuous infusion of bupivacaine Anesth Analg 1992; 75: 284–6

    Article  PubMed  CAS  Google Scholar 

  24. Mevorach DL, Perkins FM, Isaacson SA. Bupivacaine toxicity secondary to continuous caudal epidural infusion in pediatric patients. Anesth Analg 1993; 77: 1305–6

    Article  PubMed  CAS  Google Scholar 

  25. Cystic fibrosis and colonic strictures [editorial]. J Clin Gastroenterol 1995; 21: 2–5

  26. Olkkola KT, Aranko K, Luurila H, et al. A potentially hazardous interaction between erythromycin and midazolam. Clin Pharmacol Ther 1993; 53: 298–305

    Article  PubMed  CAS  Google Scholar 

  27. Hiller A, Olkkola KT, Isohanni P, et al. Unconsciousness associated with midazolam and erythromycin. Br J Anaesth 1990; 65: 826–8

    Article  PubMed  CAS  Google Scholar 

  28. Zenk KE. Challenges in providing pharmaceutical care to pediatric patients. Am J Hosp Pharm 1994; 51: 688–94

    PubMed  CAS  Google Scholar 

  29. Gilman JT, Gal P. Pharmacokinetic and pharmacodynamic data collection in children and neonates: a quiet frontier. Clin Pharmacokinet 1992; 23: 1–9

    Article  PubMed  CAS  Google Scholar 

  30. Tack ED, Perlman JM. Renal failure in sick hypertensive premature neonates receiving captopril therapy. J Pediatr 1988; 112: 805–10

    Article  PubMed  CAS  Google Scholar 

  31. Perlman JM, Volpe JJ. Neurologic complications of captopril treatment of neonatal hypertension. Pedatrics 1989; 83: 47–52

    CAS  Google Scholar 

  32. Rane A, Tomson G. Prenatal and neonatal drug metabolism in man. Eur J Clin Pharmacol 1980; 18: 9–15

    Article  PubMed  CAS  Google Scholar 

  33. Moore B. The relationship of dosage of a drug to the size of an animal treated, especially in regard to the cause of the failure to cure trypanosomiasis, and other protozoan diseases in man and in other large animals. Biochem J 1909; 4: 322–30

    Google Scholar 

  34. Holford NHG. A size standard for pharmacokinetics. Clin Pharmacokinet 1996; 30: 329–32

    Article  PubMed  CAS  Google Scholar 

  35. Du Bois D, Du Bois EF Clinical calorimetry: tenth paper. A formula to estimate the approximate surface area if height and weight be known. Arch Intern Med 1916; 17: 863

    Google Scholar 

  36. Kleiber M. The fire of life: an introduction to animal energetics. New York: Wiley, 1961

    Google Scholar 

  37. Peters HP. The ecological implications of body size. Cambridge: Cambridge University Press, 1983: 48–53

    Book  Google Scholar 

  38. Paxton JW, Young D, Robertson IG. Pharmacokinetics of acridine-4-carboximade in the rat, with extrapolation to humans. Cancer Chemother Pharmacol 1993; 32: 323–5

    Article  PubMed  CAS  Google Scholar 

  39. Cruze CA, Kelm GR, Meredith MR Interspecies scaling of tebufelone pharmacokinetic data and application to preclinical toxicology. Pharm Res 1995; 12: 895–901

    Article  PubMed  CAS  Google Scholar 

  40. Lave T, Schmitt-Hoffmann AH, Coassolo P, et al. A new extrapolation method from animals to man: application to a metabolised compound, nefarotene. Life Sci 1995; 56: 473–8

    Article  Google Scholar 

  41. Prothero JW. Scaling of blood parameters in mammals. Comp Biochem Physiol 1980; A67: 649–57

    Article  Google Scholar 

  42. Adolf EF. Quantitative relations in the physiological constitutions of animals. Science 1949; 109: 579–85

    Article  Google Scholar 

  43. Guyton AC. Measurement of the respiratory volumes of laboratory animals. Am J Physiol 1947; 150: 70–7

    PubMed  CAS  Google Scholar 

  44. Stahl WR. Scaling of respiratory variables in mammals. J Appl Physiol 1967; 22: 453–60

    PubMed  CAS  Google Scholar 

  45. British National Formulary. London: British Medical Association, 1995: 11

  46. Martindale: the extra pharmacopoeia. London: Pharmaceutical Press, 1989

  47. Catzel P, Olver R. Paediatric prescriber. Oxford: Blackwell, 1981; 8–12

    Google Scholar 

  48. Lack JA, Stuart-Taylor ME. Calculation of drug dosage and body surface area of children. Br J Anaesth 1997; 78: 601–5

    Article  PubMed  CAS  Google Scholar 

  49. Reilly JJ, Workman P. Normalisation of anti-cancer drug dosage using body weight and surface area: is it worthwhile? A review of theoretical and practical considerations. Cancer Chemother Pharmacol 1993; 32: 411–8

    Article  PubMed  CAS  Google Scholar 

  50. Morselli PL, Franco-Morselli R, Bossi L. Clinical pharmacokinetics in newborns and infants: age related differences and therapeutic implications. Clin Pharmacokinet 1980; 5: 485–527

    Article  PubMed  CAS  Google Scholar 

  51. Barret DA, Rutter N. Transdermal delivery and the premature neonate. Crit Rev Ther Drug Carrier Syst 1994; 11: 1–30

    Google Scholar 

  52. Gupta M, Brans YW. Gastric retention in neonates. Pediatrics 1978; 62: 26–9

    PubMed  CAS  Google Scholar 

  53. Grand RJ, Watkins JB, Torti FM. Development of the human intestinal tract: a review. Gastroenterology 1976: 70: 790–810

    PubMed  CAS  Google Scholar 

  54. Anderson BJ, Holford NHG, Woollard GA. Paracetamol kinetics in neonates. Anaesth Intensive Care 1997; 25: 721–2 (A)

    Google Scholar 

  55. Brown RD, Wilson JT, Kearns GL, et al. Single-dose pharmacokinetics of ibuprofen and acetaminophen in febrile children. J Clin Pharmacol 1992; 32: 231–41

    PubMed  CAS  Google Scholar 

  56. Simon GL, Gorbach SL. Intestinal flora in health and disease Gastroenterol 1984; 86: 174–93

    CAS  Google Scholar 

  57. Linday L, Dobkin JF, Wang TC, et al. Digoxin inactivation by the gut flora in infancy and childhood. Pediatrics 1987; 79: 544–8

    PubMed  CAS  Google Scholar 

  58. Friis-Hansen B. Body water compartments in children: changes during growth and related changes in body composition. Pediatrics 1961; 28: 169–81

    PubMed  CAS  Google Scholar 

  59. McRorie TI, Lynn AM, Nespeca MK, et al. The maturation of morphine clearance and metabolism. Am J Dis Child 1992; 146: 972–6

    PubMed  CAS  Google Scholar 

  60. Pokela ML, Olkkola KT, Seppala T, et al. Age-related morphine kinetics in infants. Dev Pharmacol Ther 1993; 20: 26–34

    PubMed  CAS  Google Scholar 

  61. Hertzka RE, Gauntlett IS, Fisher DM, et al. Fentanyl-induced ventilatory depression: effects of age. Anaesthesiology 1989; 70: 213–8

    Article  CAS  Google Scholar 

  62. Koehntop DE, Rodman JH, Brundage GM, et al. Pharmacokinetics of fentanyl in neonates. Anesth Analg 1986; 65: 227–32

    Article  PubMed  CAS  Google Scholar 

  63. Rowland M, Tozer TN, editors. Clinical pharmacokinetics: concepts and applications. 3rd ed. Baltimore: Williams and Wilkins, 1995

    Google Scholar 

  64. Keenan RL, Shapiro JH, Kane FR, et al. Bradycardia during anaesthesia in infants: an epidemiologic study. Anesthesiology 1994; 80: 976–82

    Article  PubMed  CAS  Google Scholar 

  65. Lerman J. Pharmacology of inhalational anaesthetics in infants and children. Paediatric Anaesthesia 1992; 2: 191–203

    Article  Google Scholar 

  66. Malviya S, Lerman J. The blood/gas solubilities of sevoflurane, isoflurane, halothane, and serum constituent concentrations in neonates and humans. Anesthesiology 1990; 72: 793–6

    Article  PubMed  CAS  Google Scholar 

  67. Lerman J, Schmitt BI, Willis MM, et al. Effects of age on the solubility of volatile anesthetics in human tissues. Anesthesiology 1986; 65: 307–11

    Article  PubMed  CAS  Google Scholar 

  68. Keenan RL, Shapiro JH, Dawson K. Frequency of anesthetic arrests in infants: effect of pediatric anesthesiologist. J Clin Anesth 1991; 3: 433–7

    Article  PubMed  CAS  Google Scholar 

  69. Anderson B, Holford N. Aspects of theophylline clearance in children. Anaesth Intensive Care 1997; 25: 497–501

    PubMed  CAS  Google Scholar 

  70. Way WL, Costley EC, Way EL. Respiratory sensitivity of the newborn infant to meperidine and morphine. Clin Pharmacol Ther 1965; 6: 454–61

    PubMed  CAS  Google Scholar 

  71. Lynn AM, Nespeca MK, Opheim KE, et al. Respiratory effects of intravenous morphine infusions in neonates, infants, and children after cardiac surgery. Anesth Analg 1993; 77: 695–701

    Article  PubMed  CAS  Google Scholar 

  72. Beyer JE, Degood DE, Ashley LC, et al. Patterns of postoperative analgesics used with adults and children following cardiac surgery. Pain 1983; 17: 71–81

    Article  PubMed  CAS  Google Scholar 

  73. Reed MD, Aronoff SC, Meyers CM, et al. Developmental pharmacokinetics of moxalactam. Antimicrob Agents Chemother 1983; 20: 383–7

    Article  Google Scholar 

  74. Montgomery CJ, McCormack JP, Reichert CC, et al. Plasma concentrations after high-dose (45 mg/kg) rectal acetaminophen in children. Can J Anaesth 1995; 42: 982–6

    Article  PubMed  CAS  Google Scholar 

  75. Brandts CH, Ndjave M, Graninger W, et al. Effects of paracetamol on parasite clearance time in Plasmodium falciparum malaria. Lancet 1997; 350: 704–9

    Article  PubMed  CAS  Google Scholar 

  76. Anderson BJ, Holford NHG, Monteleone J. Variability of concentrations after rectal paracetamol [letter]. Paediatr Anaesth 1998; 8(3): 274

    PubMed  CAS  Google Scholar 

  77. Gal P, Gilman JT. Drug disposition in neonates with patent ductus arteriosus. Ann Pharmacother 1993; 27: 1383–8

    PubMed  CAS  Google Scholar 

  78. Chang D. Influence of malignancy on the pharmacokinetics of vancomycin in infants and children. Pediatr Infect Dis J 1995; 14: 667–73

    Article  PubMed  CAS  Google Scholar 

  79. Brown TCK, Gregory M, Bell B, et al. Response to non-depolarising relaxants — electromyographic studies in children. Anaesthesia 1987; 42: 1284–6

    Article  PubMed  CAS  Google Scholar 

  80. Noble-Jamison CM, Kuzmin P, Airede KI. Hidden sources of fluid and sodium intake in ill newborns. Arch Dis Child 1986; 61: 695–6

    Article  Google Scholar 

  81. Deardorff DL. Osmotic strength, osmolality, and osmolarity. Am J Hosp Pharm 1980; 37: 504–9

    PubMed  CAS  Google Scholar 

  82. Zenk KE. Improving the accuracy of mini-volume injections. Infusion 1882; 6: 7–10

    Google Scholar 

  83. Shann F. Drug doses. 9th ed. Melbourne: Collective Pty Ltd, 1996

    Google Scholar 

  84. Mehl B. Defining excellence. Am J Hosp Pharm 1993; 50: 921–8

    PubMed  CAS  Google Scholar 

  85. Allnutt MR. Human factors in accidents. Br J Anaesth 1987; 59: 856–64

    Article  PubMed  CAS  Google Scholar 

  86. Leape LL, Bates DW, Cullen DJ, et al. Systems analysis of adverse drug events. JAMA 1995; 274: 35–43

    Article  PubMed  CAS  Google Scholar 

  87. Cohen M. Drug product characteristics that foster drug-use-system errors. Am J Hosp Pharm 1995; 52: 395–9

    CAS  Google Scholar 

  88. Greig A, Ryan J, Glucksman E. How good are doctors at estimating children’s weight? J Accident Emerg Med 1997; 14: 101–3

    Article  CAS  Google Scholar 

  89. Koren G, Barzilay Z, Greenwald M. Tenfold errors in administration of drug doses: a neglected iatrogenic disease in paediatrics. Pediatrics 1986; 77: 848–9

    PubMed  CAS  Google Scholar 

  90. Zeroing in on medication errors [editorial]. Lancet 1997; 349: 369

    Google Scholar 

  91. Robertson WO. Errors in prescribing. Am J Hosp Pharm 1995; 52: 382–5

    CAS  Google Scholar 

  92. Dasta JF, Greer ML, Speedie SM. Computers in healthcare: overview and bibliography. Ann Pharmacother 1992; 26: 109–117

    PubMed  CAS  Google Scholar 

  93. Cohen MR, Anderson RW, Attilio RM, et al. Preventing medication errors in cancer chemotherapy. Am J Health Syst Pharm 1996; 53: 737–46

    PubMed  CAS  Google Scholar 

  94. Merry AF, Peck DJ. Anaesthetists, errors in drug administration and the law. NZ Med J 1995; 108: 185–7

    CAS  Google Scholar 

  95. Pelstein PH, Callison C, White M, et al. Errors in drug computations during newborn intensive care. Am J Dis Child 1979; 133: 376–9

    Google Scholar 

  96. Koren G. Therapeutic drug monitoring principles in the neonate. Clin Chem 1997; 43(1): 222–7

    PubMed  CAS  Google Scholar 

  97. Yaffe SJ. Clinical aspects of perinatal pharmacology. Eur J Clin Pharmacol 1980; 18: 3–7

    Article  PubMed  CAS  Google Scholar 

  98. Fox GN. Minimizing prescribing errors in infants and children. Am Fam Physician 1996; 53(4): 1319–25

    PubMed  CAS  Google Scholar 

  99. Bates DW, Burrows AM, Grossman DGS, et al. Top-priority actions for preventing adverse drug events in hospitals: recommendation of an expert panel. Am J Health Syst Pharm 1996; 53: 747–51

    Google Scholar 

  100. Gadomski A. Rational use of over the counter medications in young children. JAMA 1994; 272(13): 1063–4

    Article  PubMed  CAS  Google Scholar 

  101. Kogen MD, Pappas G, Yu SM, et al. Over-the-counter medication use among US preschool-age children. JAMA 1994; 272: 1025–30

    Article  Google Scholar 

  102. Murphy MD. Individual characteristics of nurses who committed medication errors. Issues 1992; 13: 11–3

    Google Scholar 

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Anderson, B.J., Ellis, J.F. Common Errors of Drug Administration in Infants. Pediatr-Drugs 1, 93–107 (1999). https://doi.org/10.2165/00128072-199901020-00003

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