Treatment of Sickle Cell Pain

Abstract and Introduction

Abstract

Sickle cell disease affects 70,000 Americans who experience an average of 0.8 painful episodes each year. The pathophysiology of sickle cell pain is not completely understood. The disease is characterized by both acute and chronic pain syndromes. Patients with sickle cell pain often encounter barriers to receiving appropriate care, including lack of continuity of care and perceived opiate addiction. Studies describing pharmacotherapy for sickle cell pain have been primarily retrospective and uncontrolled. In analyzing the available literature regarding pathophysiology, assessment, and treatment of sickle cell pain, we found a need for increased practitioner education and inter-vention to improve the level of care provided to patients with this disease.

Introduction

Approximately 70,000 Americans have sickle cell disease, and 1000 babies are born with the disease each year.^[1] Although sickle cell disease can be present in any ethnic group, it is most common in people of African ancestry.^[2] The disease is characterized by episodes of pain. Patients experience an average of 0.8 pain episodes each year.^[3] In fact, pain crises are the most common cause for hospitalization of patients with sickle cell disease, representing 75,000 hospitalizations and $475 million in health care expenditure annually.^[2,4]

Pain is debilitating for many patients with sickle cell disease; however, not all patients experience pain episodes with the same frequency or intensity. In one survey, 38% of patients did not report a pain crisis during a 5-year evaluation period.^[2] In fact, only a few patients experienced most episodes. Of the respondents, only 5% of patients experienced three or more painful episodes a year, but these represented approximately one-third of all episodes.^[2] A correlation was reported between the number of pain crises and early mortality from sickle cell disease.^[2] Patients with risk factors for poor pain control are those who have poor coping strategies or are poorly adjusted, those with adverse social situations, and those whose lives are more profoundly affected by their pain episodes.^[5]

Many health professionals are reluctant to prescribe adequate dosages of opiates due to concerns regarding addiction and side effects.^[6] An evaluation of adequacy of pain control in 21 children with sickle cell disease found that 71% had not achieved adequate pain control during the study period.^[7] Three possible explanations were proposed: pain was inadequately assessed, choice or dosage of analgesic was inappropriate, or providers did not understand the nature of sickle cell pain.^[7]

In March 1999, the Joint Committee on Accreditation of Healthcare Organizations (JCAHO) approved standards for assessment and management of pain for inpatients and outpatients. The standards stress that patients have a right to appropriate assessment and management of their pain. In 2000, JCAHO began to determine institu-tional compliance with pain management through interviews with patients, families, and clinical staff and through review of pain-related policies and procedures.^[8]

Inadequate treatment of pain, new treatment standards, and increasing patient awareness of treatment alternatives all emphasize the need to improve the management of sickle cell pain crises. We reviewed the current literature on acute and chronic pain in patients with sickle cell disease by identifying clinical trials, case reports, and reviews in the Medline database from 1980-2001. Several other articles were identified through reference citations.

Table 1. Table 1. Studies Evaluating Opiates and Administration Routes for Patients with Sickle Cell Pain
Patients	Study Design	Drug, Route of Administration	Dosage	Results
38 children^[19]	Retrospective review of 98 hospital admissions	Morphine or meperidine, i.v.	Morphine 0.15-mg/kg bolus, then 0.07-0.1 mg/kg/hr	Patients reported better pain control with the protocol than with previous random treatment by physician.
Meperidine 1-mg/kg bolus, then 0.5-0.7 mg/kg/hr
20 adults^[28]	Randomized	Morphine, PCA vs intermittent injection	PCA group: 2-mg bolus with 1 mg PCA and 6-min lockout; may increase to 1.5 mg PCA	No significant difference in amount of morphine given (28.8 ± 13 mg vs 25.5 ± 23.5 mg), length of stay (6.5 ± 2.6 hrs vs 7.1 ± 3.6 hrs) or side effects (53% vs 47%) for intermittent group and PCA group, respectively.
Intermittent injection group: 4 mg every 30-60 min; may increase to 6 mg
66 children^[29]	Randomized, placebo-controlled	Morphine, i.v. vs p.o.	Group 1: 0.15 mg/kg i.v., then 1.9 mg/kg sustained- release tablets every 12 hrs, with immediate-release tablets for breakthrough	No significant difference in pain scores (6.3 vs 6.4), duration of opiate administration (4.2 vs 5.4 days), or side effects for p.o. and i.v., respectively.
Group 2: 0.15 mg/kg i.v., then continuous at 4 mg/kg/hr, with i.v. bolus for breakthrough
9 patients^[30]	Retrospective review of 116 emergency visits over 1 yr	Morphine, p.o.	Elixir 60 mg, then 20 mg every 30 min until pain relief or sedation over 6-8 hrs, then admit or discharge, vs i.v. meperidine	Fewer emergency visits (150 vs 116, p<0.01) and hospital admissions (19 vs 5, p<0.01) with protocol.
26 children and adolescents^[32]	Retrospective review of 60 hospital admissions	Morphine, PCA	Group 1: PCA dose of 0.25 mg/kg, basal at night 0.01-0.03 mg/kg/hr, 1-hr limit of 0.1-0.15 mg/kg	Group 1 received significantly less than group 2 (6681 vs 10,667 mg, p=0.013) and had fewer PCA days (4.9 vs 6.16, p=0.0112) and hospital days (5.033 vs 7.183, p=0.0012); no difference in side effects.
Group 2: PCA dose of 0.1-0.2 mg/kg, continuous basal 0.05-0.2 mg/kg/hr, 1-hr limit of 0.05-0.2 mg/kg
66 children^[33]	Randomized, placebo- controlled	Opiates, intermittent vs continuous	Group 1: Morphine, codeine, or meperidine, bolus every 3-4 hrs	No difference in mean dosage (0.032 vs 0.035 mg/kg/hr), significant reduction in duration of severe pain in continuous group (2 ± 1.8 days vs 0.9 ± 1 day), no difference in side effects.
Group 2: Morphine 0.004 mg/kg/hr
50 adults^[34]	Case series, switch from meperidine to morphine	Morphine, i.v.	5-mg bolus, then 5 mg/hr with unspecified bolus dose, discharged with extended-release	Emergency visits decreased by 67%, length of stay by 23%; admissions to other hospitals did not increase.
45 adults^[35]	Randomized, double-blind	Morphine vs butorphanol, i.m.	Morphine 6 mg or butorphanol 2 mg every 30-60 min	No significant difference in pain relief, discharge rates (68.6% vs 68.2%), or frequency of adverse effects (13% vs 23%).

Table 1. Table 1. Studies Evaluating Opiates and Administration Routes for Patients with Sickle Cell Pain

Patients

Study Design

Drug, Route of
Administration

Dosage

Results

38 children^[19]

Retrospective review of 98 hospital admissions

Morphine or meperidine, i.v.

Morphine 0.15-mg/kg bolus, then 0.07-0.1 mg/kg/hr

Patients reported better pain control with the protocol than with previous random treatment by physician.

Meperidine 1-mg/kg bolus, then 0.5-0.7 mg/kg/hr

20 adults^[28]

Randomized

Morphine, PCA vs intermittent injection

PCA group: 2-mg bolus with 1 mg PCA and 6-min lockout; may increase to 1.5 mg PCA

No significant difference in amount of morphine given (28.8 ± 13 mg vs 25.5 ± 23.5 mg), length of stay (6.5 ± 2.6 hrs vs 7.1 ± 3.6 hrs) or side effects (53% vs 47%) for intermittent group and PCA group, respectively.

Intermittent injection group: 4 mg every 30-60 min; may increase to 6 mg

66 children^[29]

Randomized, placebo-controlled

Morphine, i.v. vs p.o.

Group 1: 0.15 mg/kg i.v., then 1.9 mg/kg sustained- release tablets every 12 hrs, with immediate-release tablets for breakthrough

No significant difference in pain scores (6.3 vs 6.4), duration of opiate administration (4.2 vs 5.4 days), or side effects for p.o. and i.v., respectively.

Group 2: 0.15 mg/kg i.v., then continuous at 4 mg/kg/hr, with i.v. bolus for breakthrough

9 patients^[30]

Retrospective review of 116 emergency visits over 1 yr

Morphine, p.o.

Elixir 60 mg, then 20 mg every 30 min until pain relief or sedation over 6-8 hrs, then admit or discharge, vs i.v. meperidine

Fewer emergency visits (150 vs 116, p<0.01) and hospital admissions (19 vs 5, p<0.01) with protocol.

26 children and adolescents^[32]

Retrospective review of 60 hospital admissions

Morphine, PCA

Group 1: PCA dose of 0.25 mg/kg, basal at night 0.01-0.03 mg/kg/hr, 1-hr limit of 0.1-0.15 mg/kg

Group 1 received significantly less than group 2 (6681 vs 10,667 mg, p=0.013) and had fewer PCA days (4.9 vs 6.16, p=0.0112) and hospital days (5.033 vs 7.183, p=0.0012); no difference in side effects.

Group 2: PCA dose of 0.1-0.2 mg/kg, continuous basal 0.05-0.2 mg/kg/hr, 1-hr limit of 0.05-0.2 mg/kg

66 children^[33]

Randomized, placebo- controlled

Opiates, intermittent vs continuous

Group 1: Morphine, codeine, or meperidine, bolus every 3-4 hrs

No difference in mean dosage (0.032 vs 0.035 mg/kg/hr), significant reduction in duration of severe pain in continuous group (2 ± 1.8 days vs 0.9 ± 1 day), no difference in side effects.

Group 2: Morphine 0.004 mg/kg/hr

50 adults^[34]

Case series, switch from meperidine to morphine

Morphine, i.v.

5-mg bolus, then 5 mg/hr with unspecified bolus dose, discharged with extended-release

Emergency visits decreased by 67%, length of stay by 23%; admissions to other hospitals did not increase.

45 adults^[35]

Randomized, double-blind

Morphine vs butorphanol, i.m.

Morphine 6 mg or butorphanol 2 mg every 30-60 min

No significant difference in pain relief, discharge rates (68.6% vs 68.2%), or frequency of adverse effects (13% vs 23%).

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Treatment of Sickle Cell Pain

Abstract and Introduction

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