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Impact of sepsis on risk of postoperative arterial and venous thromboses: large prospective cohort study Jacques D Donzé,1 2 3 Paul M Ridker,3 4 5 Samuel R G Finlayson,6 David W Bates2 3
Ж EDITORIAL by Myles 1
Division of General Internal Medicine, Bern University Hospital, 3010 Bern, Switzerland 2 Division of General Internal Medicine and Primary Care, Brigham and Women’s Hospital, 02120 Boston, Massachusetts, USA 3 Harvard Medical School, 02115 Boston, Massachusetts, USA 4 Center for Cardiovascular Disease Prevention, Division of Preventive Medicine, Brigham and Women’s Hospital, 02215 Boston, MA 5 Division of Cardiovascular Medicine, Brigham and Women’s Hospital, 02215 Boston, MA, USA 6 Department of Surgery, University of Utah, 84132 Salt Lake City, UT, USA Correspondence to: J Donzé, Universitätsklinik für Allgemeine Innere Medizin, INSELSPITAL, Universitätspital Bern, 3010 Bern, Switzerland [email protected] Cite this as: BMJ 2014;349:g5334 doi: 10.1136/bmj.g5334
This is a summary of a paper that was published on thebmj.com as BMJ 2014;349:g5334
thebmj.com Ж Randomised trials of human albumin for adults with sepsis: systematic review and metaanalysis with trial sequential analysis of all-cause mortality (BMJ 2014;349:g4561) Ж Hydroxyethyl starch 130/0.38-0.45 versus crystalloid or albumin in patients with sepsis: systematic review with meta-analysis and trial sequential analysis (BMJ 2013;346:f839) Ж Sepsis: definition, epidemiology, and diagnosis (BMJ 2007;335:879)
STUDY QUESTION What is the impact of sepsis before a surgical procedure on the risk of postoperative arterial and venous thromboses, and does this impact vary according to the sepsis severity? SUMMARY ANSWER Preoperative sepsis represents a major determinant of postoperative arterial and venous thromboses in almost all surgical settings. This risk is already clinically important in early stages of sepsis without a proved infectious agent and increases with the severity of the inflammatory response. The risk of arterial and venous thromboses should be recognised in preoperative patients with any grade of sepsis. WHAT IS KNOWN AND WHAT THIS PAPER ADDS Arterial and venous thromboses represent common serious postoperative complications. This study showed that preoperative sepsis was an important independent risk factor for both arterial and venous thromboses, with about three times the risk of each of these complications compared with patients without evidence of preoperative sepsis.
Participants and setting Participants in our study were a random sample of adults who underwent a non-trauma major surgical procedure in up to 374 academic and community hospitals in the United States. The setting was the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database. Trained abstractors use strict standard definitions to collect data at an institutional level. Design, size, and duration This was an observational cohort study of 2 305 380 surgical procedures performed in 2005-12. Sepsis and its severity subtypes (systemic inflammatory response syndrome, sepsis, and severe sepsis/septic shock) were identified within the 48 hours before surgical procedure. The main outcome was arterial thrombosis (myocardial
infarction or stroke) and venous thrombosis (deep venous thrombosis or pulmonary embolism) within 30 days after the surgical procedure.
Main results and the role of chance Patients with preoperative systemic inflammatory response syndrome or any sepsis had three times the odds of either an arterial or venous postoperative thrombosis (odds ratio 3.1, 95% confidence interval 3.0 to 3.1). The adjusted odds ratio was 2.7 (2.5 to 2.8) for arterial thrombosis and 3.3 (3.2 to 3.4) for venous thrombosis. Compared with patients without any systemic inflammation, the adjusted odds ratios for thrombosis were 2.5 (2.4 to 2.6) in patients with a systemic inflammatory response syndrome, 3.3 (3.1 to 3.4) in patients with sepsis, and 5.7 (5.4 to 6.1) in patients with severe sepsis. In patients with preoperative sepsis, emergency and elective surgical procedures were both associated with a twofold increased odds of thrombosis. Bias, confounding, and other reasons for caution We had no information about drugs patients were already taking. Because of increases in troponin concentrations in some patients with sepsis, we cannot completely exclude overdiagnosis of arterial thrombosis in these patients, although an isolated increase of troponin was not a sufficient criterion to determine the presence of arterial thrombosis. Despite the presence of an exhaustive list of factors collected in this cohort and the careful selection of the covariates to adjust for, we cannot fully exclude residual confounding. Generalisability to other populations As our findings were from a large population from all types of hospitals across the entire US, they should be generalisable to similar populations. Study funding/potential competing interests JDD was partly supported by the Swiss National Science Foundation for his time. Several authors have links with various pharmaceutical companies. Full details are on bmj.com.
Adjusted odds ratios (95% CI) for thrombosis within 30 days after surgery in 2 305 380 patients with preoperative sepsis Sepsis severity
Arterial or venous thrombosis Arterial thrombosis Venous thrombosis
Any sepsis
SIRS*
2.5 (2.4 to 2.6)
Sepsis† 3.3 (3.1 to 3.4)
Severe sepsis‡
3.1 (3.0 to 3.1) 2.7 (2.5 to 2.8) 3.3 (3.2 to 3.4)
2.2 (2.1 to 2.4) 2.6 (2.5 to 2.7)
2.6 (2.4 to 2.8) 3.7 (3.5 to 3.9)
5.0 (4.6 to 5.4) 6.1 (5.7 to 6.5)
5.7 (5.4 to 6.1)
SIRS=systemic inflammatory response syndrome. *Defined by presence of two or more of: body temperature >38°C or 90 beats/min; respiratory rate >20 breaths/min or PaCO2 12000 cell/mm3, 10% immature (band) forms; anion gap acidosis. †SIRS plus one of: positive result on blood culture; clinical documentation of purulence or positive culture from any site thought to be causative. ‡Sepsis and documented organ and/or circulatory dysfunction.
12
27 September 2014 | the bmj
Copyright of BMJ: British Medical Journal is the property of BMJ Publishing Group and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
Impact of sepsis on risk of postoperative arterial and venous thromboses: large prospective cohort study Jacques D Donzé,1 2 3 Paul M Ridker,3 4 5 Samuel R G Finlayson,6 David W Bates2 3
Ж EDITORIAL by Myles 1
Division of General Internal Medicine, Bern University Hospital, 3010 Bern, Switzerland 2 Division of General Internal Medicine and Primary Care, Brigham and Women’s Hospital, 02120 Boston, Massachusetts, USA 3 Harvard Medical School, 02115 Boston, Massachusetts, USA 4 Center for Cardiovascular Disease Prevention, Division of Preventive Medicine, Brigham and Women’s Hospital, 02215 Boston, MA 5 Division of Cardiovascular Medicine, Brigham and Women’s Hospital, 02215 Boston, MA, USA 6 Department of Surgery, University of Utah, 84132 Salt Lake City, UT, USA Correspondence to: J Donzé, Universitätsklinik für Allgemeine Innere Medizin, INSELSPITAL, Universitätspital Bern, 3010 Bern, Switzerland [email protected] Cite this as: BMJ 2014;349:g5334 doi: 10.1136/bmj.g5334
This is a summary of a paper that was published on thebmj.com as BMJ 2014;349:g5334
thebmj.com Ж Randomised trials of human albumin for adults with sepsis: systematic review and metaanalysis with trial sequential analysis of all-cause mortality (BMJ 2014;349:g4561) Ж Hydroxyethyl starch 130/0.38-0.45 versus crystalloid or albumin in patients with sepsis: systematic review with meta-analysis and trial sequential analysis (BMJ 2013;346:f839) Ж Sepsis: definition, epidemiology, and diagnosis (BMJ 2007;335:879)
STUDY QUESTION What is the impact of sepsis before a surgical procedure on the risk of postoperative arterial and venous thromboses, and does this impact vary according to the sepsis severity? SUMMARY ANSWER Preoperative sepsis represents a major determinant of postoperative arterial and venous thromboses in almost all surgical settings. This risk is already clinically important in early stages of sepsis without a proved infectious agent and increases with the severity of the inflammatory response. The risk of arterial and venous thromboses should be recognised in preoperative patients with any grade of sepsis. WHAT IS KNOWN AND WHAT THIS PAPER ADDS Arterial and venous thromboses represent common serious postoperative complications. This study showed that preoperative sepsis was an important independent risk factor for both arterial and venous thromboses, with about three times the risk of each of these complications compared with patients without evidence of preoperative sepsis.
Participants and setting Participants in our study were a random sample of adults who underwent a non-trauma major surgical procedure in up to 374 academic and community hospitals in the United States. The setting was the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database. Trained abstractors use strict standard definitions to collect data at an institutional level. Design, size, and duration This was an observational cohort study of 2 305 380 surgical procedures performed in 2005-12. Sepsis and its severity subtypes (systemic inflammatory response syndrome, sepsis, and severe sepsis/septic shock) were identified within the 48 hours before surgical procedure. The main outcome was arterial thrombosis (myocardial
infarction or stroke) and venous thrombosis (deep venous thrombosis or pulmonary embolism) within 30 days after the surgical procedure.
Main results and the role of chance Patients with preoperative systemic inflammatory response syndrome or any sepsis had three times the odds of either an arterial or venous postoperative thrombosis (odds ratio 3.1, 95% confidence interval 3.0 to 3.1). The adjusted odds ratio was 2.7 (2.5 to 2.8) for arterial thrombosis and 3.3 (3.2 to 3.4) for venous thrombosis. Compared with patients without any systemic inflammation, the adjusted odds ratios for thrombosis were 2.5 (2.4 to 2.6) in patients with a systemic inflammatory response syndrome, 3.3 (3.1 to 3.4) in patients with sepsis, and 5.7 (5.4 to 6.1) in patients with severe sepsis. In patients with preoperative sepsis, emergency and elective surgical procedures were both associated with a twofold increased odds of thrombosis. Bias, confounding, and other reasons for caution We had no information about drugs patients were already taking. Because of increases in troponin concentrations in some patients with sepsis, we cannot completely exclude overdiagnosis of arterial thrombosis in these patients, although an isolated increase of troponin was not a sufficient criterion to determine the presence of arterial thrombosis. Despite the presence of an exhaustive list of factors collected in this cohort and the careful selection of the covariates to adjust for, we cannot fully exclude residual confounding. Generalisability to other populations As our findings were from a large population from all types of hospitals across the entire US, they should be generalisable to similar populations. Study funding/potential competing interests JDD was partly supported by the Swiss National Science Foundation for his time. Several authors have links with various pharmaceutical companies. Full details are on bmj.com.
Adjusted odds ratios (95% CI) for thrombosis within 30 days after surgery in 2 305 380 patients with preoperative sepsis Sepsis severity
Arterial or venous thrombosis Arterial thrombosis Venous thrombosis
Any sepsis
SIRS*
2.5 (2.4 to 2.6)
Sepsis† 3.3 (3.1 to 3.4)
Severe sepsis‡
3.1 (3.0 to 3.1) 2.7 (2.5 to 2.8) 3.3 (3.2 to 3.4)
2.2 (2.1 to 2.4) 2.6 (2.5 to 2.7)
2.6 (2.4 to 2.8) 3.7 (3.5 to 3.9)
5.0 (4.6 to 5.4) 6.1 (5.7 to 6.5)
5.7 (5.4 to 6.1)
SIRS=systemic inflammatory response syndrome. *Defined by presence of two or more of: body temperature >38°C or 90 beats/min; respiratory rate >20 breaths/min or PaCO2 12000 cell/mm3, 10% immature (band) forms; anion gap acidosis. †SIRS plus one of: positive result on blood culture; clinical documentation of purulence or positive culture from any site thought to be causative. ‡Sepsis and documented organ and/or circulatory dysfunction.
12
27 September 2014 | the bmj
Copyright of BMJ: British Medical Journal is the property of BMJ Publishing Group and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
