[JAMA作者回复]:低收入国家全身性感染的早期复苏治疗 | 中国病理生理学会危重病医学专业委员会
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Comment & Response

February 13, 2018

Early Resuscitation for Adults With Sepsis in a Low-income Country—Reply

Matthew W. Semler, Ben Andrews, Gordon R. Bernard

JAMA. 2018;319(6):614-615. doi:10.1001/jama.2017.20410

In Reply 回复

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.


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.


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.


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。


1. Kumar  A, Roberts  D, Wood  KE,  et al.  Duration of hypotension before initiation of effective antimicrobial therapy is the critical determinant of survival in human septic shock.  Crit Care Med. 2006;34(6):1589-1596.PubMedGoogle Scholar Crossref
2. Seymour  CW, Gesten  F, Prescott  HC,  et al.  Time to treatment and mortality during mandated emergency care for sepsis.  N Engl J Med. 2017;376(23):2235-2244.PubMed | Google Scholar | Crossref
3. Rivers  E, Nguyen  B, Havstad  S,  et al; Early Goal-Directed Therapy Collaborative Group.  Early goal-directed therapy in the treatment of severe sepsis and septic shock.  N Engl J Med. 2001;345(19):1368-1377.PubMed | Google Scholar | Crossref
4. Yealy  DM, Kellum  JA, Huang  DT,  et al; ProCESS Investigators.  A randomized trial of protocol-based care for early septic shock.  N Engl J Med. 2014;370(18):1683-1693.PubMed | Google Scholar | Crossref
5. Peake  SL, Delaney  A, Bailey  M,  et al; ARISE Investigators; ANZICS Clinical Trials Group.  Goal-directed resuscitation for patients with early septic shock.  N Engl J Med. 2014;371(16):1496-1506.PubMed | Google Scholar | Crossref


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