Buchanan Iris D, Woodward Maribel, Reed George W
Morehouse School of Medicine, Atlanta, Georgia 30310, USA.
Pediatr Blood Cancer. 2005 Oct 15;45(5):716-24. doi: 10.1002/pbc.20403.
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.
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.
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.
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.
镰状细胞病（SCD）的标志是反复发作的疼痛性血管闭塞事件（VOC），这也是SCD患者住院的最常见原因。麻醉药，尤其是吗啡，与液体水化一起是疼痛发作的标准治疗方法，但与通常称为急性胸综合征（ACS）的急性肺部事件的发生有关。ACS的发生通常先于急性感染、疼痛发作、肋骨梗死、骨髓梗死和脂肪栓塞。其病理生理学仍然是多因素的，并且已成为早期死亡的最常见原因。既往ACS发作会增加反复发生急性肺部事件和随后发生肺动脉高压的可能性。盐酸纳布啡（Nubain）是一种具有吗啡止痛效力的阿片类药物，但尚未研究其与ACS发生的关联，也未在镰状细胞人群中将其与吗啡在疼痛控制疗效方面进行比较。
我们回顾性分析了1999年1月至2002年12月期间因血管闭塞性危机入住亚特兰大三家儿童医院的5至19岁患者的病历。使用计算机化搜索工具，通过国际疾病分类第九版（ICD-9）诊断代码282.60和282.62识别患者。ACS的最终出院诊断定义为入院后至出院前胸部X光片上新出现的肺部浸润。我们计算出需要160例患者入院，以85%的检验效能检测两个治疗组之间ACS发生率约20%的差异。
共有37例（21%）ACS发作。其中，26例（29%）在吗啡组，11例（12%）在纳布啡组（P<0.01）。接受吗啡治疗的患者入院时白细胞计数更高的可能性更大（P<0.05），且更有可能采用持续静脉输注给药（49%对3%，P<0.001）。他们的住院时间也比接受纳布啡治疗的患者更长（中位住院时间3天对4天，吗啡组），P<0.001。
疼痛发作期间ACS的发生是多因素的，但阿片类药物的选择可能会增加这一发生率。使用纳布啡的患者发生ACS的可能性较小，且住院时间较短。这些结果因使用PCA持续镇痛输注而受到混淆。然而，纳布啡在治疗镰状细胞疼痛发作方面可能是吗啡的一种替代药物。下一步进行比较这两种镇痛药的前瞻性临床试验会更好。
