EBQ:Early versus delayed administration of norepinephrine in patients with septic shock.

Complete Journal Club Article

Xiaowu Bai, Wenkui Yu*, Wu Ji, Zhiliang Lin, Shanjun Tan, Kaipeng Duan, Yi Dong, Lin Xu and Ning Li*. "Early versus delayed administration of norepinephrine in patients with septic shock". Critical Care. 2014. :.
PubMed PDF

Clinical Question

• In adult patients with septic shock have improved hospital mortality in patients who receive delayed norepinephrine?

Conclusion

• In patients with septic shock, early administration of norepinephrine is associated with increase survival rate

Major Points

• Overall mortality of septic shock patients is 37.6%
• Delaying norepinephrine even if given within 6 hours by 1 hour was associated with an increase in mortality by 5.3%
• norepinephrine increases preload, improves cardiac output and renal perfusion

Study Design

• Retrospective cohort study from Jan 2011 to December 2012
• 2 general surgical intensive care units at a tertiary care hospital
• Septic shock is defined as presence of infection with hypotension SBP<90 mmHg, decrease of 40 mmHg in SBP from patients baseline MAP or MAP<65;

Population

Patient Demographics

• Median age: 67 years
• Male: 59%
• Most common source of sepsis: pulmonary (40%), abdominal (28%), urinary (18%)

Inclusion Criteria

• Adults with septic shock as defined by Sepsis-3 criteria
• Requiring vasopressor support

Exclusion Criteria

• Cardiac arrest prior to enrollment
• Moribund patients with expected death within 24 hours
• Already receiving vasopressors for >24 hours

Interventions

• Early norepinephrine group: vasopressor initiated within 1 hour of meeting septic shock criteria
• Delayed norepinephrine group: vasopressor initiated after initial fluid resuscitation (typically >1 hour after shock recognition)
• Both groups received standard sepsis care including antibiotics, source control, and fluid resuscitation per Surviving Sepsis Campaign guidelines

Outcomes

Primary Outcome

*28 day mortality

• improved outcomes when norepinephrine was delivered within 2 hours of septic shock onset compared to more than 2 hours
• Patients with early NE had improved MAPs, and lower lactates with less amount of time hypotensive and with fewer amounts of NE given

Criticisms

• Retrospective study design limits ability to establish causation
• Definition of "early" vs "delayed" was based on arbitrary time cutoffs
• Potential for immortal time bias: patients who survived long enough to receive delayed vasopressors may have been less sick
• Fluid volumes administered prior to vasopressor initiation were variable and not standardized
• Results may have been confounded by other time-dependent interventions (antibiotics, source control)

Funding

• None reported