Benefits of Patient-Controlled Analgesia without Continuous Infusion for the Treatment of Sickle Cell Disease Vaso-Occlusive Crisis Pain

Introduction:  Sickle cell disease (SCD) is a chronic illness characterized by unpredictable episodes of pain, cumulative organ damage, and high-health care utilization rates.  Intravenous opioids are considered a mainstay in the management of acute vaso-occlusive pain crisis (VOC). In 2007, van Beers and colleagues demonstrated that the use of patient-controlled analgesia (PCA) results in significant reductions in morphine consumption with equivalent response on measurements of pain and quality of life, and this is largely accepted by SCD providers.   There remains controversy regarding the method of administration of opioids via PCA, with studies examining varying ratios of continuous to demand dosing.  PCA with basal infusion plus demand dosing seems to be preferred by the hematology community whereas emerging data in other populations, demonstrate adequate pain control and reduced rates of opioid-related adverse events with the use of demand only approaches.  In October 2012, as part of a quality improvement initiative at the Children's Hospital at Montefiore, we revised our pain management guidelines to exclude the routine use of basal infusions in our PCA protocol.  In addition, pain management consultation was requested to assist in management of PCA, particularly as it related to the appropriate use of basal infusions when indicated and timely transition to oral analgesics. Short-term methadone during the inpatient stay with a short taper post discharge was utilized for improved and long-acting analgesia in patients that did not improve rapidly on the standard regimen.

Methods: We conducted a retrospective analysis of patients with  SCD < 21 years of age, admitted for VOC 3-7 times/year, comparing patient admissions in 2011 versus 2013, pre- and post-revision of the pain protocol as described above. Baseline variables evaluated include demographic and clinical characteristics outlined in Table 1. Primary outcomes include total opioid utilization during inpatient admission, total hours on intravenous PCA and length of stay (LOS).  Secondary outcomes include rates of acute chest syndrome, hypoxia, exchange transfusion and transfer to the pediatric intensive care unit.

Results:  A total of 144 admissions were included in the analysis, 73 in 2011 and 72 in 2013.  Baseline demographics and clinical characteristics were similar in both  groups (Table 1).  In 2011, 72/73 patient admissions were treated with PCA with basal infusion compared to only 1/72 patient in 2013.  Total opioid utilization during inpatient admission, total PCA hours and LOS were significantly reduced in the 2013 group compared to the 2011 group with no significant difference in admit pain to discharge pain (Table 2).  Furthermore, patients in the 2013 group demonstrated a significantly lower incidence in episodes of hypoxia and acute chest syndrome (Table 2)

Conclusions:  In conclusion, we demonstrate the feasibility and benefits of demand only PCA in the management of VOC pain.  Superiority of the demand only PCA approach needs to be rigorously evaluated in a randomized prospective study.

Table 1: Baseline demographic and clinical characteristics by admissions:

	2011 (n=73)	2013 (n=72)	P-value
Age (years)	16.3 ± 3.5	15.4 ± 3.3	0.40
Gender    M    F	39 (53.4%) 34 (46.6%)	32 (44.4%) 40 (55.6%)	0.62
Race    Black    Multiracial	60 (82.2%) 13 (17.8%)	61 (84.7%) 11 (15.3%)	0.87
Ethnicity    Non-Hispanic    Hispanic	55 (75.3%) 18 (24.7%)	55 (76.4%) 17 (23.6%)	0.85
Genotype    Hbg SS    Hgb SC	68 (93.2%) 5 (6.8%)	59 (81.9%) 13 (18.1%)	0.18
Weight (kg)	57.3 ± 17.6	54.7 ± 19.3	0.45
Opioid tolerant    Y    N	9 (12.3%) 64 (87.7%)	3 (4.2%) 69 (95.8%)	0.25
Hydroxyurea    Y    N	44 (60.3%) 29 (39.7%)	33 (45.8%) 39 (54.2%)	0.50
Hemoglobin (g/dL)	8.7 ± 1.8	8.6 ± 1.6	0.85
HgbS %    HgbF%	77.5 ± 10.4 10.9 ± 6.9	77.7 ± 15.1 6.5 ± 5.6	0.97 0.10

Table 2: Comparison of primary and secondary outcomes by admissions:

	2011 (n=73)	2013 (n=72)	P-value
Total opioid utilization during inpatient admission* (mg IV ME/kg**)	13.3 ± 33.8	3.6 ± 3.0	0.0003
Total PCA hours	153.2 ± 103.2	80.0 ± 45.4	<0.0001
Length of stay (days)	7.5 ± 5.0	5.5 ±7.4	0.002
Change in pain score (Admit pain to discharge pain)	5.5 ± 3.1	5.7 ± 3.2	0.82
Hypoxia	21/73 (28.8%)	5/72 (6.9%)	0.0008
Acute chest syndrome	16/73 (21.9%)	2/72 (2.8%)	0.0043

*all oral and IV opioids were included

** mg IV ME/kg = milligrams of intravenous morphine equivalents per kilogram