The Epidemiology of Extremity Threat and Amputation after Vasopressor-Dependent Sepsis

Ann Am Thorac Soc. 2022 Apr;19(4):625-632. doi: 10.1513/AnnalsATS.202105-547OC.


Rationale: Extremity threat and amputation after sepsis is a well-publicized and devastating event. However, there is a paucity of data about the epidemiology of extremity threat after sepsis onset. Objectives: To estimate the incidence of extremity threat with or without surgical amputation in community sepsis. Methods: Retrospective cohort study of adults with Sepsis-3 hospitalized at 14 academic and community sites from 2013 to 2017. Vasopressor-dependent sepsis was identified by administration of epinephrine, norepinephrine, phenylephrine, vasopressin, or dopamine for more than 1 hour during the 48 hours before to 24 hours after sepsis onset. Outcomes included the incidence of extremity threat, defined as acute onset ischemia, with or without amputation, in the 90 days after sepsis onset. The association between extremity threat, demographics, comorbid conditions, and time-varying sepsis treatments was evaluated using a Cox proportional hazards model. Results: Among 24,365 adults with sepsis, 12,060 (54%) were vasopressor dependent (mean ± standard deviation age, 64 ± 16 years; male, 6,548 [54%]; sequential organ failure assessment [SOFA], 10 ± 4). Of these, 231 (2%) patients had a threatened extremity with 26 undergoing 37 amputations, a risk of 2.2 (95% confidence interval [CI], 1.4-3.2) per 1,000, and 205 not undergoing amputation, a risk of 17.0 (95% CI, 14.8-19.5) per 1,000. Most amputations occurred in lower extremities (95%), a median (interquartile range) of 16 (6-40) days after sepsis onset. Compared with patients with no extremity threat, patients with threat had a higher SOFA score (11 ± 4 vs. 10 ± 4; P < 0.001), serum lactate (4.6 mmol/L [2.4-8.7] vs. 3.1 [1.7-6.0]; P < 0.001), and more bacteremia (n = 37 [37%] vs. n = 2,087 [26%]; P < 0.001) at sepsis onset. Peripheral vascular disease, congestive heart failure, SOFA score, and norepinephrine equivalents were significantly associated with extremity threat. Conclusions: The evaluation of a threatened extremity resulting in surgical amputation occurred in 2 per 1,000 patients with vasopressor-dependent sepsis.

Keywords: amputation; peripheral ischemia; sepsis; symmetric peripheral gangrene; vasopressor.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Amputation, Surgical*
  • Humans
  • Lower Extremity / surgery
  • Male
  • Middle Aged
  • Retrospective Studies
  • Risk Factors
  • Sepsis* / epidemiology
  • Treatment Outcome