February 13, 2018
Matthew W. Semler, Ben Andrews, Gordon R. Bernard
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Drs Nedel and Deutschendorf highlight 2 key considerations for the interpretation of our trial and the management of patients with sepsis across settings: (1) timing of antibiotic administration and (2) volume of intravenous fluid.
Nedel和Deutschendorf医生指出了在解读我们临床试验结果以及不同场合下治疗全身性感染患者的2个要点：(1)使用抗生素的时机；及(2)静脉输液量
First, Nedel and Deutschendorf point out that delays in antibiotic administration for patients with sepsis and hypotension have been consistently associated with higher mortality.1,2 They note that attempting to simultaneously deliver multiple therapies (eg, intravenous fluids, vasopressors, blood transfusion, and antibiotics) with limited clinical personnel and limited intravenous access could inadvertently delay antibiotic administration and worsen outcomes.
首先，Nedel和Deutschendorf医生指出，对于合并低血压的全身性感染患者，延误抗生素治疗与高病死率相关。他们认为，在有限的临床人力及静脉通路条件下，试图同时进行多种治疗（例如，静脉输液，升压药物，输血和抗生素）不可避免的造成抗生素治疗延误，加重临床预后。
To ensure that the time to antibiotic administration did not differ between groups in our trial, we had a dedicated study nurse to facilitate the timely administration of antibiotics ordered by clinicians in both the sepsis protocol and usual care groups. Unlike fluid and vasopressor receipt, time to antibiotic administration was not statistically significantly different between groups in our trial. Moreover, in prior studies, each 1-hour delay in antibiotic administration was associated with an absolute increase in mortality in the range of 5% to 10%,1,2 suggesting a difference between groups in time to antibiotic administration in the range of 1.5 to 3.0 hours would be required to explain the absolute difference in mortality of 15.1% observed in our trial.
为保证我们的临床试验两组患者抗生素治疗时间没有差异，我们有专门的研究护士，确保全身性感染方案治疗组及常规治疗组患者及时应用临床医生处方的抗生素。与液体治疗及升压药物治疗不同，我们的研究中两组间抗生素治疗时间并无统计学差异。而且，既往研究显示，抗生素治疗每延误一个小时，伴随病死率绝对值增加5-10%，提示两组间抗生素使用时间需要相差1.5-3.0个小时，才能解释我们试验中观察到的病死率15.1%的差异。
Second, Nedel and Deutschendorf inquire whether the volume of intravenous fluid administered in the intervention (sepsis protocol) group of our trial was greater than that administered in prior sepsis resuscitation trials or recommended by the Surviving Sepsis Campaign. The median volume of intravenous fluid administered between emergency department presentation and 6 hours in the intervention group of our trial was 3.5 L. The mean volume administered during the same time interval in prior sepsis resuscitation trials was 5.0 L,3 5.1 L,4 and 4.5 L.5
其次，Nedel和Deutschendorf医生提出质疑，我们试验中干预组静脉输液量查过了既往全身性感染复苏试验的用量，也超过了拯救全身性感染行动指南的推荐用量。我们的研究中，干预组患者急诊就诊最初6小时内静脉输液中位数为3.5 L。既往全身性感染复苏试验中同一时间段的平均输液量为5.0 L，5.1 L和4.5 L。
Although weight could not be measured for nonambulatory patients in our study setting, we measured upper arm circumference, which estimates body mass index among patients who are unable to ambulate. Nearly three-fourths of patients in our trial had an upper arm circumference of 22.5 cm or less, which correlates with a body mass index of less than 18.5 kg/m2. Thus, the median volume of intravenous fluid administered between emergency department presentation and 6 hours was approximately 70 mL/kg in our trial, similar to the approximately 70 mL/kg administered during the same time interval in the recent Protocolized Care for Early Septic Shock trial conducted in the United States.4
尽管我们的研究中未测量卧床患者的体重，但我们侧量了上臂臂围，后者能够估测不能活动患者的体质指数。我们研究中近3/4的患者上臂臂围不超过22.5 cm，相当于体质指数不足18.5 kg/m2。因此，我们的试验中，最初6个小时静脉输液中位数约为70 ml/kg，与近期美国进行的ProCESS研究同一时间段的输液量(70 ml/kg)相似。
