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Health professional perceptions of opioid dependence among patients with pain
Brief Reports
Health Professional Perceptions of Opioid Dependence Among Patients With Pain RON D. WALDROP, MD, CRIS MANDRY, MD The purpose of this study was to determine the percentage of patients perceived by health professionals to be opioid dependent among all patients presenting with pain and specifically among sickle cell patients with pain. Surveys were completed by all staff, residents, and nurses at an urban teaching hospital with an emergency department population consisting primarily of lower socioeconomic patients of African-American origin. The surveys requested a percentage estimate of all pain patients and sickle cell patients with pain presenting to this hospital who they perceived to be opioid dependent. The estimated percentage of opioid dependent patients presenting to the emergency department with pain was 4% for staff (P < .05, n = 14), 9% for residents (n = 31), and 7% for nurses (n = 41), and the estimates for sickle cell patients presenting with pain only were 8%, 17%, and 13% respectively (P < .05). All health professional groups surveyed estimated opioid dependence in patients with pain far in excess of that shown in previous studies. It is unknown whether pain medication are withheld inappropriately by physicians who perceived patients with pain to be opioid dependent, and that this deserved further study especially among sickle cell patients. (Am J Emerg Med 1995;13:529-531. Copyright © 1995 by W.B. Saunders Company)
Pain is a frequent reason for hospital visits, especially for patients with sickle cell disease.~ Appropriate therapy for pain often includes the use of parenteral opioids such as morphine. 2 It is well known that health professionals are at times reluctant to give parenteral opioids out of a fear of addiction, recreational use, or economic gain, often resulting in the undertreatment of pain. 3-7 Given the current confusion about the definitions of drug addiction and dependence, the judgment by a health professional concerning drug dependency in a patient with pain may be quite subjective. 1"3"4 Hence, physicians may inappropriately withhold parenteral opioids from patients with pain if they perceive them to be drug-dependent. The purpose of this study was to determine the percentage of patients believed to be opioid dependent by health professionals among all patients presenting to the hospital with pain, and specifically sickle cell patients with pain as their only complaint.
From the Department of Emergency Medicine, Earl K. Long Medical Center, Baton Rouge, LA. Manuscript received August 10, 1994; revision accepted October 14, 1994. Address reprint requests to Ron D. Waldrop, MD, Earl K. Long Medical Center, Department of Emergency Medicine, 5825 Airline Highway, Baton Rouge, LA 70805. Key Words: Pain, narcotic-dependent, sickle cell disease. Copyright © 1995 by W.B. Saunders Company 0735-6757/95/1305-000955.00/0
METHODS The study was performed in an urban teaching hospital with 65,000 annual emergency department (ED) visits, of which 18% were due to pain in 1993 (ED logs). Annually, approximately 300 visits (25 monthly) to the ED are because of sickle cell disease with pain leading to approximately 150 admissions (12 to 13 monthly). Surveys were mailed to all internal medicine, family practice, pediatric and ED attendings, residents, and nurses who staff those services on October 1, 1993. The number of sickle cell patients with pain reported to be treated monthly was compared with hospital logs to verify accuracy of respondents' memories. Mean monthly patients with pain treated and percentage perceived to be opioid dependent were determined for the three health professional groups. Groups' means were statistically compared using one-way ANOVA, and level of significance was chosen as P < .05. RESULTS All staff physicians, residents, and nurses surveyed returned fully completed surveys that were included for evaluation. Mean monthly patients treated and the percentage perceived to be opioid dependent by each health professional group within each pain group are shown in Table 1. The mean monthly number of sickle cell patients reportedly treated was similar to the monthly volume of sickle cell patients seen in the ED (25) and admitted (12 to 13), verifying relative accuracy of the respondent's memory. Staff physicians perceived a significantly smaller percentage of patients with pain to be opioid dependent in both groups, whereas a significantly higher percentage of sickle cell patients with pain were perceived to be opioid dependent in all health professional categories. There was no significant differences in variables between individual hospital services in any health professional group. DISCUSSION Previous studies on the use of parenteral opioids in pain, including sickle cell patients, have shown the development of opioid dependence in less than 1%. 8-1° The present study showed subjective perception by a variety of health professionals well in excess of this number for both a general population of pain patients and specifically sickle cell pain patients. It is unknown what percentage of the total population surveyed are opioid dependent, although a recent drug screening study of all patients committed to a psychiatric or substance abuse facility from this facility showed less than 1% opioid abuse. This excessive perception of opioid dependence in patients with pain has been shown previously in 529
530
TABLE 1.
AMERICAN JOURNAL OF EMERGENCY MEDICINE • Volume 13, Number 5 • September 1995
Summary of Responses by Health Professionals Surveyed About Opioid Dependency, in Pain Patients All Pain Patients
Staff physicians Resident physicians Nurses
Sickle Cell Patients
N Respondents
Monthly Patients"
Percentage Narcotic Dependent1"
Monthly Patients
Percentage Narcotic Dependent
14 31 41
11 -+ 2.3~t 16 -+ 2.7 20 -+ 1.8
4 - 2.0§ 'll 9 --- 3.7§ 7 --- 2.4§
9+_2.1 14 +_3.0 15 -+ 2.6
8 --- 2.1 II t7 --- 4.2 13 --- 2.6
* Monthly patients treated for pain. 1" Percentage of patients with pain perceived to be opioid dependent. :~ x -+ standard deviation. § P < .05 by one-way ANOVA between pain groups. ii p < .05 by one-way ANOVA within pain groups.
health professionals caring for postoperative and medical patients.6"11 Much of the confusion about opioid dependency lies in an incomplete understanding of the physiological and psychological drug dependence. 12-~5The prolonged use of opioids is associated with the physiological phenomena of tolerance and dependence and is commonly seen in the intensive care setting. 16-22 Tolerance is manifested by a decrease in the pharmacological effects of the drug with its repeated administration, or by increase in dose requirements in order to attain the same clinical effect. Tolerance to opioids results from the adaptation of neuronal cells, rather than from any changes in drug metabolism. Dependence requires the continued administration of the drug in order to prevent withdrawal symptoms, which include agitation, dysphoria, tachycardia, tachypnea, nasal congestion, piloerection, nausea, temperature instability, feeding intolerance, and myalgia. 18,19 Tolerance to opioids may develop within a few hours after the administration of morphine, fentanyl, and meperidine. 23-25 The differences between tolerance, physiological dependence, psychological dependence, and addiction must be clearly understood by clinicians practicing in a critical care setting such as the emergency department. These terms are often used inappropriately and interchangeably in the literature, with important implications for clinical practice. Tolerance and physiological dependence are based on neurochemical mechanisms, whereas psychological dependence is characterized by the craving for a substance because of its euphoric properties. Addiction has been defined as "behavioral pattern of drug use, characterized by overwhelming involvement with the compulsive use of a drug, the securing of its supply, and a high tendency to relapse after withdrawal. ''23 The use of opioids for analgesia or sedation rarely results in psychological dependence or addiction. 26-3~ Thus, tolerance and dependence are phenomena that are clinically important only in their influence on the choice of appropriate dosages and weaning schedules. It has even been suggested that the risk of addiction can be disregarded in light of the severe pain and the abrupt ending of the pain encountered in patients with sickle cell disease. 2°'29 Therefore, the fear of opioid dependence or addiction is probably not warranted in sickle cell patients who complain of pain and request treatment. Limitations of this study include the survey design that is dependent on respondent memory and a relatively small
number of respondents. Fortunately, the same population was surveyed each time, making comparisons between the two reliable. In addition, ED logs verified the accuracy of the respondents' memory. Another limitation is the unique population served by this hospital consisting primarily of lower socioeconomic patients of African American origin. Our results may not be applicable to hospitals with different demographic characteristics. These findings do suggest that further studies are needed to determine if physician belief and perception about drug dependence in patients presenting with pain may inappropriately alter treatment in patients with pain. In conclusion, all health professional groups surveyed perceived percentages of opioid dependence in patients with pain far in excess of that shown in previous prospective studies with staff physicians perceiving significantly less than residents or nurses. A significantly higher percentage of sickle cell patients with pain were perceived to be opioid dependent compared with estimated percentages of all pain patients presenting to an urban hospital. The authors thank Rhonda Ledeune, and Drs. Phil Brantley and Glenn Jones for their valuable assistance in this publication. REFERENCES
1. Shapiro BS: The management of pain in sickle cell disease. Pediatr Clin North Am 1989;36:1029-1045 2. Charache S (ed): Management and Therapy of Sickle Cell Disease. US Department of Health and Human Services, NIH Publication, 1989;89:2117 3. Yaster M, Desphande J: Management of pediatric pain with opioid analgesics. J Pediatr 1988;113:421-429 4. Bojanowski C: Use or protocols for ED patients with sickle cell anemia. J Emerg Nurs 1989;15:83-87 5. Alavi JB: Sickle cell anemia: Pathophysiology and treatment. Med Clin North Am 1984;68:545-556 6. Marks RM, Sachar EJ: Undertreatment of medical inpatients with narcotic analgesics. An n Intern Med 1973;78:173-181 7. Cohen FL: Postsurgical pain relief: Patients' status and nurses' medication choices. Pain 1980;9:265-274 8. Morrison RA: Update on sickle cell disease: Incidence of addiction and choice of opioid in pain management. Pediatr Nurs 1991 ;17:503 9. Porter J, Jick H: Addiction rare in patients treated with narcotics. N Engl J Med 1980;302:123 10. Miller RR: Analgesics. Drug effects in hospitalized patients. In: Miller RR, Greenblatt DJ, eds: New York, John Wiley, 1976, pp 133-164 11. Weis OF, Sriwantanokul K, Alloza JL et al: Attitudes of patients, housestaff, and nurses toward postoperative analgesic care. Anesth Analg 1983;62:70-74
WALDROP AND MANDRY • OPIOID DEPENDENCE IN PAIN PATIENTS
12. Brookoff D, Poloman R: Treating sickle cell pain like cancer pain. Ann Intern Med 1992;116:364-368 13. Morrison RA, Vedra DA: Pain management in the child with sickle cell disease. Pediatr Nurs 1989;15:595-599 14. Smith JA: Letter to the editor. Ann Intern Med 1992;117: 263 15. Jaffe JH: Drug addiction and drug abuse. In Gilman AG, Rail TW, Nies AS, et al (eds): The Pharmacologic Basis of Therapeutics (ed 8). New York, NY, Pergamon Press, 1990, pp 522-573 16. Jaffe JH, Martin WR: Opioid analgesics and antagonists. In: Gilman AG, Rail TW, Nies AS, et al (eds): The Pharmacologic Basis of Therapeutics (ed 8). New York, Pergamon Press, 1990, pp 485-521 17. Shafer A, White PF, Schuttler J, et al: Use of a fentanyl infusion in the intensive care unit: Tolerance to its anesthetic effects. Anesthesiology 1983;59:245-248 18. Norton SJ: Aftereffects of morphine and fentanyl analgesia: A retrospective study. Neonatal Network 1988;7:25-28 19. Maguire DP, Maloney P: A comparison of fentanyl and morphine use in neonates. Neonatal Network 1988;7:27-32 20. Tobias JD, Schleien CL, Haun SE: Methadone as treatment for iatrogenic narcotic dependence in pediatric intensive care unit patients. Crit Care Med 1990;18:1292-1293 21. Arnold JH, Truog RD, Orav TM, et al: Tolerance and dependence in neonates sedated with fentanyl during extracorporeal membrane oxygenation. Anesthesiology 1990;73:1136-1140
531
22. Arnold JH, Truog RD, Scavone JM, et al: Changes in the pharmacodynamic response to fentanyl in neonates during continuous infusion. J Pediatr 1991;119:639-643 23. Jaffe JH: Drug addiction and drug abuse. In: Gilman AG, Rail TW, Nies AS, et al (eds): The Pharmacologic Basis of Therapeutics, ed 8. New York, Pergamon Press, 1990, pp 522-573 24, Finnegan LP: Effects of maternal opiate abuse on the newborn. Fed Proc 1985;44:2314-2317 25. Eisenberg RM: Short-term tolerance to morphine: Effects of indomethacin. Life Sci 1982;30:1399-1405 26. Eaton DG, Wertheim D, Oozeer R, et al: The effect of pethidine on the neonatal EEG. Dev Med Child Neurol 1992;34:155163 27. Newman RG: The need to redefine "addiction." N Engl J Med 1983;308:1096-1098 28. Flemming AF: Sickle cell disease: A Handbook for the General Clinician. New York, Churchill Livingstone, 1982, pp 117-120 29. Gradoff B: Sickle cell anemia in children. Issues Compr Pediatr Nurs 1983;6:295-306 30. Taub A: Opioid analgesics in the treatment of chronic intractable pain of non-neoplastic origin. Narcotic Analgesics in Anesthesiology. In: Collins JG, Kitahata LM, eds: Baltimore, MD. Williams & Wilkens, 1982;199-208 31. Charache S: Advances in the understanding of sickle cell anemia. Hosp Pract 1986;15:173-190
Health Professional Perceptions of Opioid Dependence Among Patients With Pain RON D. WALDROP, MD, CRIS MANDRY, MD The purpose of this study was to determine the percentage of patients perceived by health professionals to be opioid dependent among all patients presenting with pain and specifically among sickle cell patients with pain. Surveys were completed by all staff, residents, and nurses at an urban teaching hospital with an emergency department population consisting primarily of lower socioeconomic patients of African-American origin. The surveys requested a percentage estimate of all pain patients and sickle cell patients with pain presenting to this hospital who they perceived to be opioid dependent. The estimated percentage of opioid dependent patients presenting to the emergency department with pain was 4% for staff (P < .05, n = 14), 9% for residents (n = 31), and 7% for nurses (n = 41), and the estimates for sickle cell patients presenting with pain only were 8%, 17%, and 13% respectively (P < .05). All health professional groups surveyed estimated opioid dependence in patients with pain far in excess of that shown in previous studies. It is unknown whether pain medication are withheld inappropriately by physicians who perceived patients with pain to be opioid dependent, and that this deserved further study especially among sickle cell patients. (Am J Emerg Med 1995;13:529-531. Copyright © 1995 by W.B. Saunders Company)
Pain is a frequent reason for hospital visits, especially for patients with sickle cell disease.~ Appropriate therapy for pain often includes the use of parenteral opioids such as morphine. 2 It is well known that health professionals are at times reluctant to give parenteral opioids out of a fear of addiction, recreational use, or economic gain, often resulting in the undertreatment of pain. 3-7 Given the current confusion about the definitions of drug addiction and dependence, the judgment by a health professional concerning drug dependency in a patient with pain may be quite subjective. 1"3"4 Hence, physicians may inappropriately withhold parenteral opioids from patients with pain if they perceive them to be drug-dependent. The purpose of this study was to determine the percentage of patients believed to be opioid dependent by health professionals among all patients presenting to the hospital with pain, and specifically sickle cell patients with pain as their only complaint.
From the Department of Emergency Medicine, Earl K. Long Medical Center, Baton Rouge, LA. Manuscript received August 10, 1994; revision accepted October 14, 1994. Address reprint requests to Ron D. Waldrop, MD, Earl K. Long Medical Center, Department of Emergency Medicine, 5825 Airline Highway, Baton Rouge, LA 70805. Key Words: Pain, narcotic-dependent, sickle cell disease. Copyright © 1995 by W.B. Saunders Company 0735-6757/95/1305-000955.00/0
METHODS The study was performed in an urban teaching hospital with 65,000 annual emergency department (ED) visits, of which 18% were due to pain in 1993 (ED logs). Annually, approximately 300 visits (25 monthly) to the ED are because of sickle cell disease with pain leading to approximately 150 admissions (12 to 13 monthly). Surveys were mailed to all internal medicine, family practice, pediatric and ED attendings, residents, and nurses who staff those services on October 1, 1993. The number of sickle cell patients with pain reported to be treated monthly was compared with hospital logs to verify accuracy of respondents' memories. Mean monthly patients with pain treated and percentage perceived to be opioid dependent were determined for the three health professional groups. Groups' means were statistically compared using one-way ANOVA, and level of significance was chosen as P < .05. RESULTS All staff physicians, residents, and nurses surveyed returned fully completed surveys that were included for evaluation. Mean monthly patients treated and the percentage perceived to be opioid dependent by each health professional group within each pain group are shown in Table 1. The mean monthly number of sickle cell patients reportedly treated was similar to the monthly volume of sickle cell patients seen in the ED (25) and admitted (12 to 13), verifying relative accuracy of the respondent's memory. Staff physicians perceived a significantly smaller percentage of patients with pain to be opioid dependent in both groups, whereas a significantly higher percentage of sickle cell patients with pain were perceived to be opioid dependent in all health professional categories. There was no significant differences in variables between individual hospital services in any health professional group. DISCUSSION Previous studies on the use of parenteral opioids in pain, including sickle cell patients, have shown the development of opioid dependence in less than 1%. 8-1° The present study showed subjective perception by a variety of health professionals well in excess of this number for both a general population of pain patients and specifically sickle cell pain patients. It is unknown what percentage of the total population surveyed are opioid dependent, although a recent drug screening study of all patients committed to a psychiatric or substance abuse facility from this facility showed less than 1% opioid abuse. This excessive perception of opioid dependence in patients with pain has been shown previously in 529
530
TABLE 1.
AMERICAN JOURNAL OF EMERGENCY MEDICINE • Volume 13, Number 5 • September 1995
Summary of Responses by Health Professionals Surveyed About Opioid Dependency, in Pain Patients All Pain Patients
Staff physicians Resident physicians Nurses
Sickle Cell Patients
N Respondents
Monthly Patients"
Percentage Narcotic Dependent1"
Monthly Patients
Percentage Narcotic Dependent
14 31 41
11 -+ 2.3~t 16 -+ 2.7 20 -+ 1.8
4 - 2.0§ 'll 9 --- 3.7§ 7 --- 2.4§
9+_2.1 14 +_3.0 15 -+ 2.6
8 --- 2.1 II t7 --- 4.2 13 --- 2.6
* Monthly patients treated for pain. 1" Percentage of patients with pain perceived to be opioid dependent. :~ x -+ standard deviation. § P < .05 by one-way ANOVA between pain groups. ii p < .05 by one-way ANOVA within pain groups.
health professionals caring for postoperative and medical patients.6"11 Much of the confusion about opioid dependency lies in an incomplete understanding of the physiological and psychological drug dependence. 12-~5The prolonged use of opioids is associated with the physiological phenomena of tolerance and dependence and is commonly seen in the intensive care setting. 16-22 Tolerance is manifested by a decrease in the pharmacological effects of the drug with its repeated administration, or by increase in dose requirements in order to attain the same clinical effect. Tolerance to opioids results from the adaptation of neuronal cells, rather than from any changes in drug metabolism. Dependence requires the continued administration of the drug in order to prevent withdrawal symptoms, which include agitation, dysphoria, tachycardia, tachypnea, nasal congestion, piloerection, nausea, temperature instability, feeding intolerance, and myalgia. 18,19 Tolerance to opioids may develop within a few hours after the administration of morphine, fentanyl, and meperidine. 23-25 The differences between tolerance, physiological dependence, psychological dependence, and addiction must be clearly understood by clinicians practicing in a critical care setting such as the emergency department. These terms are often used inappropriately and interchangeably in the literature, with important implications for clinical practice. Tolerance and physiological dependence are based on neurochemical mechanisms, whereas psychological dependence is characterized by the craving for a substance because of its euphoric properties. Addiction has been defined as "behavioral pattern of drug use, characterized by overwhelming involvement with the compulsive use of a drug, the securing of its supply, and a high tendency to relapse after withdrawal. ''23 The use of opioids for analgesia or sedation rarely results in psychological dependence or addiction. 26-3~ Thus, tolerance and dependence are phenomena that are clinically important only in their influence on the choice of appropriate dosages and weaning schedules. It has even been suggested that the risk of addiction can be disregarded in light of the severe pain and the abrupt ending of the pain encountered in patients with sickle cell disease. 2°'29 Therefore, the fear of opioid dependence or addiction is probably not warranted in sickle cell patients who complain of pain and request treatment. Limitations of this study include the survey design that is dependent on respondent memory and a relatively small
number of respondents. Fortunately, the same population was surveyed each time, making comparisons between the two reliable. In addition, ED logs verified the accuracy of the respondents' memory. Another limitation is the unique population served by this hospital consisting primarily of lower socioeconomic patients of African American origin. Our results may not be applicable to hospitals with different demographic characteristics. These findings do suggest that further studies are needed to determine if physician belief and perception about drug dependence in patients presenting with pain may inappropriately alter treatment in patients with pain. In conclusion, all health professional groups surveyed perceived percentages of opioid dependence in patients with pain far in excess of that shown in previous prospective studies with staff physicians perceiving significantly less than residents or nurses. A significantly higher percentage of sickle cell patients with pain were perceived to be opioid dependent compared with estimated percentages of all pain patients presenting to an urban hospital. The authors thank Rhonda Ledeune, and Drs. Phil Brantley and Glenn Jones for their valuable assistance in this publication. REFERENCES
1. Shapiro BS: The management of pain in sickle cell disease. Pediatr Clin North Am 1989;36:1029-1045 2. Charache S (ed): Management and Therapy of Sickle Cell Disease. US Department of Health and Human Services, NIH Publication, 1989;89:2117 3. Yaster M, Desphande J: Management of pediatric pain with opioid analgesics. J Pediatr 1988;113:421-429 4. Bojanowski C: Use or protocols for ED patients with sickle cell anemia. J Emerg Nurs 1989;15:83-87 5. Alavi JB: Sickle cell anemia: Pathophysiology and treatment. Med Clin North Am 1984;68:545-556 6. Marks RM, Sachar EJ: Undertreatment of medical inpatients with narcotic analgesics. An n Intern Med 1973;78:173-181 7. Cohen FL: Postsurgical pain relief: Patients' status and nurses' medication choices. Pain 1980;9:265-274 8. Morrison RA: Update on sickle cell disease: Incidence of addiction and choice of opioid in pain management. Pediatr Nurs 1991 ;17:503 9. Porter J, Jick H: Addiction rare in patients treated with narcotics. N Engl J Med 1980;302:123 10. Miller RR: Analgesics. Drug effects in hospitalized patients. In: Miller RR, Greenblatt DJ, eds: New York, John Wiley, 1976, pp 133-164 11. Weis OF, Sriwantanokul K, Alloza JL et al: Attitudes of patients, housestaff, and nurses toward postoperative analgesic care. Anesth Analg 1983;62:70-74
WALDROP AND MANDRY • OPIOID DEPENDENCE IN PAIN PATIENTS
12. Brookoff D, Poloman R: Treating sickle cell pain like cancer pain. Ann Intern Med 1992;116:364-368 13. Morrison RA, Vedra DA: Pain management in the child with sickle cell disease. Pediatr Nurs 1989;15:595-599 14. Smith JA: Letter to the editor. Ann Intern Med 1992;117: 263 15. Jaffe JH: Drug addiction and drug abuse. In Gilman AG, Rail TW, Nies AS, et al (eds): The Pharmacologic Basis of Therapeutics (ed 8). New York, NY, Pergamon Press, 1990, pp 522-573 16. Jaffe JH, Martin WR: Opioid analgesics and antagonists. In: Gilman AG, Rail TW, Nies AS, et al (eds): The Pharmacologic Basis of Therapeutics (ed 8). New York, Pergamon Press, 1990, pp 485-521 17. Shafer A, White PF, Schuttler J, et al: Use of a fentanyl infusion in the intensive care unit: Tolerance to its anesthetic effects. Anesthesiology 1983;59:245-248 18. Norton SJ: Aftereffects of morphine and fentanyl analgesia: A retrospective study. Neonatal Network 1988;7:25-28 19. Maguire DP, Maloney P: A comparison of fentanyl and morphine use in neonates. Neonatal Network 1988;7:27-32 20. Tobias JD, Schleien CL, Haun SE: Methadone as treatment for iatrogenic narcotic dependence in pediatric intensive care unit patients. Crit Care Med 1990;18:1292-1293 21. Arnold JH, Truog RD, Orav TM, et al: Tolerance and dependence in neonates sedated with fentanyl during extracorporeal membrane oxygenation. Anesthesiology 1990;73:1136-1140
531
22. Arnold JH, Truog RD, Scavone JM, et al: Changes in the pharmacodynamic response to fentanyl in neonates during continuous infusion. J Pediatr 1991;119:639-643 23. Jaffe JH: Drug addiction and drug abuse. In: Gilman AG, Rail TW, Nies AS, et al (eds): The Pharmacologic Basis of Therapeutics, ed 8. New York, Pergamon Press, 1990, pp 522-573 24, Finnegan LP: Effects of maternal opiate abuse on the newborn. Fed Proc 1985;44:2314-2317 25. Eisenberg RM: Short-term tolerance to morphine: Effects of indomethacin. Life Sci 1982;30:1399-1405 26. Eaton DG, Wertheim D, Oozeer R, et al: The effect of pethidine on the neonatal EEG. Dev Med Child Neurol 1992;34:155163 27. Newman RG: The need to redefine "addiction." N Engl J Med 1983;308:1096-1098 28. Flemming AF: Sickle cell disease: A Handbook for the General Clinician. New York, Churchill Livingstone, 1982, pp 117-120 29. Gradoff B: Sickle cell anemia in children. Issues Compr Pediatr Nurs 1983;6:295-306 30. Taub A: Opioid analgesics in the treatment of chronic intractable pain of non-neoplastic origin. Narcotic Analgesics in Anesthesiology. In: Collins JG, Kitahata LM, eds: Baltimore, MD. Williams & Wilkens, 1982;199-208 31. Charache S: Advances in the understanding of sickle cell anemia. Hosp Pract 1986;15:173-190