Background: The hallmark of sickle cell disease (SCD) is recurrent, painful vaso-occlusive episodes (VOC) and is the most common reason for hospitalization in SCD patients. Narcotics, particularly morphine, along with fluid hydration are standard treatments for painful episodes but have been associated with the development of acute pulmonary events commonly referred to as acute chest syndrome (ACS). The development of ACS is often preceded by acute infections, painful episodes, rib infarction, bone marrow infarction, and fat embolism. Its pathophysiology remains multifactorial and has become the most common reason for early mortality. Previous episodes of ACS increase the likelihood of repeated acute pulmonary events and subsequent pulmonary hypertension. Nalbuphine hydrochloride (Nubain) is an opioid with the pain relieving potency of morphine but has not been studied for its association in the development of ACS or compared with morphine in its efficacy of pain control in the sickle cell population.
Procedure: We reviewed the medical records retrospectively of patients between the age of 5 and 19 years, admitted for vaso-occlusive crisis to the three children's hospitals in Atlanta between January 1999 and December 2002. A computerized search tool was used to identify patients using the International Classification of Diseases Ninth Revision (ICD-9) diagnosis code 282.60 and 282.62. The final discharge diagnosis of ACS was defined as a new pulmonary infiltrate on chest radiograph after admission and before discharge. We calculated the need for 160 patient admissions for 85% power to detect a difference of approximately 20% in incidence of ACS between the two treatment groups.
Results: There were a total of 37 (21%) episodes of ACS. Of these, 26 (29%) were in the morphine group and 11 (12%) were in the Nubain group (P < 0.01). Patients receiving morphine were more likely to have higher white cell counts on admission (P < 0. 05), and to use continuous infusion for medication administration (49% vs. 3%), P < 0. 001. They also had longer hospital stays than patients who received Nubain (median stay 3 days vs. 4 days, morphine), P < 0. 001.
Conclusions: The development of ACS during painful episodes is multi-factorial, but opioid selection may increase this rate. Patients on Nubain were less likely to develop ACS, and they had shorter hospital stays. These results were confounded by use of continuous analgesia infusion with PCA. However, Nubain may provide an alternative to morphine in the treatment of sickle cell pain episodes. A prospective clinical trial comparing these two analgesics would be a preferable next step.