SARS临床诊断病例1291例糖皮质激素治疗不良反应分析

目的:探讨严重急性呼吸综合征(severe acute respiratory syndrome,SARS)治疗中糖皮质激素(glucocorticosteroids,GCS)的使用与不良反应的关系.方法:收集北京市SARS病历资料,建立数据库,回顾分析1 291例临床诊断SARS病例.按照GCS起始剂量、日最大剂量和累积剂量分组,均换算为甲泼尼龙(methyprednisonlone,MP)剂量.使用SAS 8.10软件统计GCS相关不良反应,包括血糖增高(≥7.8 mmoL/L)、低钾血症(＜3.5 mmol/L)、低钙血症(＜2.12 mmol/L)、收缩压升高[≥140 mm Hg(1 mm Hg=0.133 kPa)]及舒张压升高(≥90 mm Hg).结果:GCS组1 084例,未用GCS组207例.GCS平均日使用剂量总趋势是递减,早期日平均剂量(中位数)为160 mg/d,10天后下降,13天降到80 mg/d.GCS组病程中最高血糖(8.68±4.80)mmol/L,未用GCS组(6.39±3.71)mmoL/L,两组比较差异有显著性(P＜0.001).MP起始≥80 mg/d,MP最大≥160 mg/d以及MP累积≥3 000 mg各组的平均血糖均明显升高.使用GCS后第1～2周血糖升高最显著,而后逐渐下降.MP累积≥3 000 mg组血糖增高且持续时间延长,与其它组比较差异有显著性(P＜0.05).GCS组病程中最低血钾为(3.66±0.50)mmoL/L,低钾持续时间1(1,75)天,与未用GCS组(4.01±0.51)mmol/L,1(1,9)天比较差异具有显著性(P＜0.05).GCS使用后第1周血钾降低最明显,第2周血钾回升.MP起始≥320 mg/d、MP最大≥320 mg/d、MP累积≥3 000 mg与较低剂量组比较,血钾明显降低(P＜0.001);且低钾持续时间长,到第3周才回升.GCS组低血钙持续19(1,74)天,未用GCS组为8(1,32)天,两组比较差异有显著性(P＜0.05).低血钙持续时间随最大剂量、累积剂量增加而延长.MP累积＜999 mg组与未用GCS组比较低血钙持续时间相近.GCS使用后收缩压和舒张压逐渐升高,第4周升高最显著.结论:血糖增高水平、低血钾水平和持续时间与GCS的剂量和疗程关系密切.GCS影响低血钙持续时间,使收缩压和舒张压逐渐升高.使用适当剂量的GCS(MP起始＜159 mg/d,MP最大＜159 mg/d、MP累积＜2 999 mg)可以避免血糖、血钾、血钙的明显异常.使用GCS较大剂量时密切监测上述指标变化对临床治疗具有重要价值.

Side effects of glucocorticosteroids in the management of 1 291 patients of SARS

OBJECTIVE: To analysis the relationship between glucocorticosteroids (GCS) usage and side effects in the treatment of severe acute respiratory syndrome (SARS). METHODS: All clinical records of probable SARS patients in Beijing were collected and input into an Epi6 database, in which 1 291 patients had entire information and met the clinical criteria of SARS. The usage of GCS and GCS associated side effects were analyzed retrospectively. RESULTS: Patients accepted GCS therapy were 83.96% (n=1 084), whereas 16.04%(n=207) did not take GCS. The average dosage of GCS was 160 mg/d in the first week, and then reduced to 80 mg/d and 40 mg/d in the second and the third weeks, respectively. Initial blood glucose, systolic pressure (SBP), and diastolic pressure (DBP) were no significant difference between GCS group and non-GCS group. The highest blood glucose during the treatment in GCS group was markedly higher than that in non-GCS group [(8.68+/-4.80) mmol/L vs (6.39+/-3.71) mmol/L, P<0.05)]. The highest blood glucose and average blood glucose after initiation of GCS therapy were elevated in GCS group. The levels of blood glucose were correlated with the initial, maximum, and cumulative GCS dosages. Average blood glucose was increased markedly in groups with MP(Initial) > or =80 mg/d (Methyprednisonlone), MP(Maximal) > or =160 mg/d, or MP(Cumulative) > or = 3000 mg. The blood glucose grew up significantly in the first and the second weeks in the treatment with GCS, and then returned to normal level gradually. Hyperglycemia duration in the group with MP(Cumulative) > or =3000 mg persisted longer than that in the other groups (P< 0.05). The lowest serum potassium during the treatment and the duration of hypokalemia in GCS group were significantly different from that in non-GCS group [(3.66+/-0.50) mmol/L vs (4.01+/-0.51) mmol/L, P< 0.001 ;1(1, 75) days vs 1(1, 9) days, P<0.05, respectively]. Average serum potassium and the duration of hypokalemia were related to the dosages of GCS. Serum potassium reached its nadir in the first week of GCS treatment and then grew up in the second week. In groups with MP(Initial) > or =320 mg/d, MP(Maximal) > or =320 mg/d, and MP(Cumulative) > or =3000 mg, the level of serum potassium was lower and the duration of hypokalemia was longer than that in other groups. They began to returned to normal level in the third week. Administration of GCS prolonged the time of hypocalcemia[19 (1, 74) days in GCS group vs 8 (1, 32) days in non-GCS group, P< 0.05]. The duration of hypocalcemia was prolonged according to the increasing of the maximal or the cumulative dosage of GCS. However, the duration of hypocalcemia in group with MP(Cumulative) <999 mg was similar to that in non-GCS group (P > 0.05). After GCS administration, SBP and DBP were increased gradually, and reached their peaks in the fourth week [SBP(117.2+/-14.0) mm Hg and DBP (72.5+/-9.1) mm Hg vs SBP (120.0+/-12.5) mm Hg and DBP (74.5+/-8.7) mm Hg, P< 0.05, 1 mm Hg=0.133 kPa]. CONCLUSION: Hyperglycemia and hypokalemia are correlated with GCS dosage and duration. Administration with GCS influences SBP, DBP, and duration of hypocalcemia. Appropriate low dosage of GCS (MP(Initial) and MP(Maximal) < 159 mg/d, MP(Cumulative)< 2999 mg) causes few changes of blood glucose, serum potassium, and blood calcium. It is important to monitor laboratory findings during the treatment with GCS.