Ammann Roland A, Teuffel Oliver, Agyeman Philipp, Amport Nadine, Leibundgut Kurt
Department of Pediatrics, University of Bern, Bern, Switzerland.
Department of Pediatrics, University of Bern, Bern, Switzerland; Division of Oncology, Medical Services of the Statutory Health Insurance Baden-Württemberg, Tübingen, Germany.
PLoS One. 2015 Feb 11;10(2):e0117528. doi: 10.1371/journal.pone.0117528. eCollection 2015.
The temperature limit defining fever (TLDF) is based on scarce evidence. This study aimed to determine the rate of fever in neutropenia (FN) episodes additionally diagnosed by lower versus standard TLDF.
In a single center using a high TLDF (39.0°C tympanic temperature, LimitStandard), pediatric patients treated with chemotherapy for cancer were observed prospectively. Results of all temperature measurements and CBCs were recorded. The application of lower TLDFs (LimitLow; range, 37.5°C to 38.9°C) versus LimitStandard was simulated in silicon, resulting in three types of FN: simultaneous FN, diagnosed at both limits within 1 hour; earlier FN, diagnosed >1hour earlier at LimitLow; and additional FN, not diagnosed at LimitStandard.
In 39 patients, 8896 temperature measurements and 1873 CBCs were recorded during 289 months of chemotherapy. Virtually applying LimitStandard resulted in 34 FN diagnoses. The predefined relevantly (≥15%) increased FN rate was reached at LimitLow 38.4°C, with total 44 FN, 23 simultaneous, 11 earlier, and 10 additional (Poisson rate ratioAdditional/Standard, 0.29; 95% lower confidence bound, 0.16). Virtually applying 37.5°C as LimitLow led to earlier FN diagnosis (median, 4.5 hours; 95% CI, 1.0 to 20.8), and to 53 additional FN diagnosed. In 51 (96%) of them, spontaneous defervescence without specific therapy was observed in reality.
Lower TLDFs led to many additional FN diagnoses, implying overtreatment because spontaneous defervescence was observed in the vast majority. Lower TLDFs led as well to relevantly earlier diagnosis in a minority of FN episodes. The question if the high TLDF is not only efficacious but as well safe remains open.
定义发热的温度阈值(TLDF)依据的证据不足。本研究旨在确定采用较低温度阈值与标准温度阈值额外诊断的中性粒细胞减少伴发热(FN)发作的发生率。
在一个采用高温度阈值(鼓膜温度39.0°C,标准阈值)的单中心,对接受癌症化疗的儿科患者进行前瞻性观察。记录所有体温测量结果和全血细胞计数(CBC)。在计算机模拟中应用较低的温度阈值(低阈值;范围为37.5°C至38.9°C)与标准阈值进行对比,从而产生三种类型的FN:同时性FN,在1小时内在两个阈值下均被诊断;早期FN,在低阈值下比标准阈值提前>1小时被诊断;以及额外FN,在标准阈值下未被诊断。
在39例患者中,化疗的289个月期间记录了8896次体温测量结果和1873次全血细胞计数。实际应用标准阈值导致34例FN诊断。在低阈值38.4°C时达到了预先定义的相关(≥15%)升高的FN发生率,共有44例FN,其中23例同时性、11例早期和10例额外(泊松率比额外/标准,0.29;95%下置信限,0.16)。实际将37.5°C作为低阈值导致更早的FN诊断(中位数,4.5小时;95%CI,1.0至20.8),并诊断出53例额外的FN。其中51例(96%)在实际中观察到未经特殊治疗体温自行下降。
较低的温度阈值导致许多额外的FN诊断,这意味着存在过度治疗,因为绝大多数情况下观察到体温自行下降。较低的温度阈值也导致少数FN发作的诊断明显提前。高温度阈值是否不仅有效而且安全的问题仍然悬而未决。