Impact of Early Analgesia on Hospitalization for Sickle Cell Pain Crisis

National Institutes of Health guidelines for management of sickle cell acute pain suggests the use of an individualized prescribing protocol to improve outcomes for patients suffering from acute pain. The evidence that individualized pain plans improve clinical outcomes is limited and the recommendation is based on consensus opinion. Prior to implementing individualized inpatient SCD pain plans, we sought to evaluate the time required to achieve maximum opioid dose without individualized prescribing protocols and its negative impact on length of stay.

Methods: We conducted an 18-month retrospective cohort study of all SCD pediatric patients admitted from the Emergency Department (ED) for SCD pain. We recorded the ED admission time, order entry time for the maximum opioid dose (mg) during the hospitalization, time that maximum opioid dose was delivered, and time of discharge orders. Maximum opioid dose was defined as total hourly cumulative dose received in oral morphine equivalents. The primary endpoint was time (hours) required to achieve maximum opioid dosage. Secondary endpoints included: total inpatient hours, hours until discharge after a maximum opioid dose had been reached, and the impact of current SCD modifying therapy (hydroxyurea, transfusion, both, or none). Since we plan to first pilot individualized pain plans in patients with recurrent pain events, we a priori defined patients with repeated pain events as those with ≥3 pain admissions during an 18-month period. A priori we dichotomized achievement of maximum opioid dose as "early" (maximum opioid dose ordered within 24 hours from admission) or "late" (ordered >24 hours from admission). Each pain admission was considered an independent event. We performed descriptive statistics, t-test or Wilcoxon for continuous variables, and Fisher's exact test or Chi-squared test for categorical variables, using JMP Pro 12 (Cary, NC).

Results: We identified 179 pain admission events among 92 participants over 18 months (range: 1 to 9 events/patient). Data revealed 50% (n=90) admission events occurred in females. The mean age for these admission events was 13.5 years (range: 0.5-19). Genotypes included: HbSS or HbSB0 thalassemia (n=68 (74%)), HbSC (n=21 (23%)), HbSB+ thalassemia (n=3 (3%)). SCD modifying therapy categories included: 97 (54%) participants prescribed hydroxyurea (HU), 23 (13%) receiving transfusion therapy, 11 (6%) receiving transfusion and prescribed HU, and 48 (27%) no SCD therapy. The mean time elapsed until the order for the maximum total daily opioid dose was entered was 24 (SD 42) hours and the mean time until the maximum opioid dose was delivered was 37.3 (SD 48.9) hours. The mean time to maximum opioid order was similar among SCD modifying therapy categories (p=0.3). The mean total hospitalization time was 101 hours (range: 15-455 hours). There was no statistical difference in mean total hospitalization time based on current SCD modifying therapy (p=0.4).

We identified 91 admission events among 19 participants that required repeat pain admissions. Participants with repeat pain admission events required more time to achieve a maximum opioid dose than those with two or less pain admissions (31.1 vs 17.5 hours, p=0.03) despite having non-significant differences in time to discharge after the maximum opioid dose was ordered (82.5 vs 70.0 hours, p=0.2). Among repeat admission participants, 60 events (66%) were categorized as "early" achievement of a maximum opioid dose and 31 (34%) were categorized as "late." Participants with "early" maximum opioid orders had significantly shorter length of total hospital stay (early: 78±54 vs late: 183±96 hours, p<0.0001) as well as shorter time to discharge after that maximum order was placed (early: 71±52 vs late: 105±69 hours, p=0.01). Current SCD therapies did not have an impact on time to maximum opioid order (p=0.4) or total hospital stay (p=0.2).

Conclusion: It is important to quickly achieve appropriate analgesia for pediatric SCD patients suffering with pain. Participants with frequent pain admissions that achieved earlier analgesia, as determined by maximum opioid dose within 24 hours, required shorter hospitalizations than patients that required longer titration to maximum opioid dose. Individualized pain plans should be prospectively evaluated to determine their impact on early achievement of analgesia and decreasing hospitalization length of stay.