Sepsis in Unique Populations - NJHA · L\ukemia accounts for 28% of all cancers diagnosed in...

Sepsis in Unique PopulationsChrista Schorr, DNP, MSN, RN, FCCM, NEA-BC

Associate Professor of Medicine, CMSRUClinical Nurse Scientist, CUH

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NJHA January 24, 2020

Disclosures

• No financial disclosures• Member of the Surviving Sepsis Campaign (SSC) Steering Committee• Member of the SSC Guidelines- Group Head for Long term outcomes

and goals of care• Member of SCCM Thrive Committee

Objectives

Sepsis and Cancer Sepsis and Transplantation Sepsis and Surgery

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Sepsis in People with Cancer

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American Cancer Society https://www.cancer.org/research/cancer-facts-statistics/all-cancer-facts-figures/cancer-facts-figures-2019.html 2019 report.

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Presenter

Presentation Notes

Since 1991, there have been more than 2.6 million fewer cancer deaths as a result of 25 years of consistent declines in cancer deaths rates.

In 2019, there were an estimated 1,762,450

new cancer cases diagnosed and 606,880

cancer deaths in the United States.

https://www.cancer.org/research/cancer-facts-statistics/all-cancer-facts-figures/cancer-facts-figures-2019.html

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https://www.cancer.org/research/cancer-facts-statistics/all-cancer-facts-figures/cancer-facts-figures-2019.html 7

Presenter

Presentation Notes

It is estimated that more than 1.7 million new cases of cancer will be diagnosed in 2019. Prostate cancer is the most common cancer among males (20%), followed by lung (13%) and colorectal (9%) cancers. Among females, breast (30%), lung (13%), and colorectal (7%) cancers are the most common. Rankings based on estimates should be interpreted with caution because they are model-based projections.

https://www.cancer.org/research/cancer-facts-statistics/all-cancer-facts-figures/cancer-facts-figures-2019.html 8

Presenter

Presentation Notes

This slide shows cancer incidence rates in children (ages 0-14 years) and adolescents (ages 15-19 years) by cancer type according to the International Classification of Childhood Cancers. This system is more appropriate for children because it categorizes cancers based on a combination of both histology (microscopic structure) and tumor location, rather than location alone. Leukemia accounts for 28% of all cancers diagnosed in children, but just 13% of cancers diagnosed in adolescents. Cancer registries were mandated by law to begin reporting benign and borderline malignant brain and central nervous system tumors on January 1, 2004. Reporting was expanded to include these cancers because benign tumors cause disruption to normal function similar to malignant tumors and because the prognosis for benign and malignant tumors is often similar. During 2011-2015, approximately one-quarter of all brain tumors diagnosed in children and more than one-half of those in adolescents were benign or borderline malignant.

Hensley MK et al. Crit Care Med 2019; 47:1310–1316

More than one in five sepsis hospitalizations were

cancer related

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Presenter

Presentation Notes

There were 27,481,517 hospitalizations in NRD 2013–2014, of which 1,104,363 (4.0%) were for sepsis and 4,150,998 (15.1%) were cancer related (i.e., had any diagnostic code indicating malignancy). A total of 234,641 cancer-related hospitalizations (5.7%) were for sepsis. Median age 70 years-most Medicare beneficiaries.-Most had 1 organ dysfunction, median LOS 8 days, most common sites for infection respiratory 37.7% GU 26.5% and GI 10.5% in hospital mortality 21.3%

10Hensley MK et al. Crit Care Med 2019; 47:1310–1316

Presenter

Presentation Notes

There were 27,481,517 hospitalizations in NRD 2013–2014, of which 1,104,363 (4.0%) were for sepsis and 4,150,998 (15.1%) were cancer related (i.e., had any diagnostic code indicating malignancy). A total of 234,641 cancer-related hospitalizations (5.7%) were for sepsis. Median age 70 years-most Medicare beneficiaries.-Most had 1 organ dysfunction, median LOS 8 days, most common sites for infection respiratory 37.7% GU 26.5% and GI 10.5% in hospital mortality 21.3%

Organ dysfunction

Site of infection

LOS & mortality

In-Hospital Cancer-Related Sepsis Mortality by Age Group

Presenter

Presentation Notes

cancer-related sepsis remained higher in both pediatric (adjusted OR, 1.7; 95% CI, 1.4–2.2) and adult cohorts (adjusted OR, 1.6; 95% CI, 1.5–1.6). Among adults, the adjusted absolute increase in in-hospital mortality was largest in younger adults and declined with increasing age until there was no difference in in-hospital mortality among cancer related versus non–cancer-related sepsis hospitalization at age 85 years old and older: 18–25 years (adjusted OR, 3.9; 95% CI, 3.3–4.5); 26–44 years (adjusted OR, 3.2; 95% CI, 3.0–3.4); 45–64 years (adjusted OR, 2.2; 95% CI, 2.1–2.2); 65–79 years (adjusted OR, 1.6; 95% CI, 1.5–1.6); 80–85 years (adjusted OR, 1.2; 95% CI, 1.2–1.3); and greater than 85 years (adjusted OR, 1.0; 95% CI, 1.0–1.1)

Outcomes

• In hospital mortality in cancer related sepsis was 28% compared to 20% in non-cancer related sepsis.

• In-hospital mortality was higher in hematologic and undifferentiated tumor types compared to solid tumors.

• The burden of acute organ dysfunction was similar between the two groups.

• More than one in five sepsis hospitalization was followed by a 30-day readmission.

Hensley MK et al. Crit Care Med 2019; 47:1310–1316 13

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Presenter

Presentation Notes

Hellenic sepsis study 14 researchers and clinicians in Greece started in 2010 operate as a CRO doing research and education. Patients with history of stage I/II solid tumor inactive cancer matched for age, severity, type of infection and comorbidities.

Dimopoulos G et al. 2019 BMC Infectious Diseases15

Dimopoulos G et al. 2019 BMC Infectious Diseases16

Presenter

Presentation Notes

Greece -Risk factors for 28 day mortality-Variables being significantly different btwn the two groups were septic shock, acute kidney injury, and hx of stage I/II solid malignancy among non survivors; hx of coronary heart disease was more common for survivors

Clinical Implications in Cancer Patients

• Mortality difference between cancer-related and non–cancer-related sepsis may be declining over time as a result of changes in cancer treatment, immune suppression therapies and growing awareness of sepsis.

• Patients with cancer may present earlier with signs of infection and receive treatment sooner.

• Educate cancer patients and their families about infection and sepsis.• Do they have a thermometer at home?• Do they have a clear plan when they are concerned?• Who should they contact in an emergency?

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https://www.cdc.gov/sepsis/pdfs/cancer-infection-and-sepsis-fact-sheet.pdf 18

Sepsis and Transplant Recipients

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36,528 transplants

performed in 2018.

About 80/day.62% Male; 38%

female

https://www.organdonor.gov/statistics-stories/statistics.html20

Presenter

Presentation Notes

36,528 transplants were performed in 2018 – a new record high for the sixth consecutive year. Each day, about 80 people receive organ transplants. In 2018, about 62% of organ recipients were male; 38% female. More than 85,000 corneal transplants were performed in 2018. More than 1 million tissue transplants are performed each year.

Schachtner t et al. Transpl Infect Dis. 2017; 19:e12695.

• 112 of 957 kidney transplant recipients (KTRs) with sepsis.• 31 developed severe sepsis or septic shock• 30 KTRs died from sepsis

• Five year survival was 70.3% with sepsis vs 88.2% without (p=0.001)

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Presenter

Presentation Notes

Germany 2001-2012 Only those admitted to the ICU were included Several patients had multiple sepsis events Compared those with sepsis to those without

Risk factors associated with sepsis

Schachtner t et al. Transpl Infect Dis. 2017; 19:e12695.22

• This was a matched, case-control propensity-adjusted study. Conditional logistic regression was performed for risk factor analysis, and Cox proportional hazards regression for survival analysis.

• 369 pts (123 cases; 246 controls) 1:2Kalil, A. C. Et al. (2014). Clinical Infectious Diseases, 60(2), 216-222. 23

Presenter

Presentation Notes

Threehundredsixty-ninepatients(123cases;246controls)diagnosed with blood culture–proven sepsis were matched 1:2byage,sex,and hospital location. The distribution of allografts was 36.6% kidney, 34.1%liver,13% kidney-pancreas,7.3%smallbowel/liver,5.7%heart/lung, and3.3%multivisceral.

No transplant

Transplant

No transplant

Transplant

Compared to nontransplant pts, organ transplant was associated with a 78% lower 28-day mortality (HR=0.22 [95% CI, .09–.54], P=.001

Compared to nontransplant pts, organ transplant was associated with a 57% lower 90-day mortality (HR=0.43 [95% CI, .20–.89], P=.025

Kalil, A. C. Et al. (2014). Clinical Infectious Diseases, 60(2), 216-222. 24

Presenter

Presentation Notes

This is contrary to the traditional belief that once transplant patients develop a bloodstream infection they would have worse survival outcomes due to their immunosuppressed status. How could this be explained? A recent growing body of evidence strongly suggests that the overt inflammatory and coagulation responses associated with sepsis have more detrimental effects on survival outcomes than the infectious microorganisms themselves [6,7];hence, some degree of immunomodulation—more specifically, some degree of immunosuppression—may be of benefit to these patients. This hypothesis is supported by our findings.

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Risk factors associated with sepsis

• Heart recipients- pre-transplant hospitalization, post-op tracheal intubation for >1 day, high dose steroids, allograft rejection, CMV infection and post-transplant reintubation

• Kidney recipients- anastomotic leaks, contamination of the perfusate or allograft, presence of urinary catheters, ureteral stents, central venous catheters, recent diagnosis of wound infection, and advanced age at the time of transplantation

• Liver recipients- Biliary and enteric contamination, poor baseline medical condition, prolonged length of liver transplantation procedure, and extended ICU stay in the post-operative period

Kalil AC & Opal SM Curr Infect Dis Rep (2015) 17:3226

Kalil AC & Opal SM Curr Infect Dis Rep (2015) 17:3227

Presenter

Presentation Notes

Sepsis in the Severely Immunocompromised Patient- Differential diagnoses

Principles of therapeutic management for sepsis that apply to all allograft types1. Rapid initiation of intravenous antibiotics 2. Rapid diagnosis 3. Source control4. Aggressive search for pathologies that mimic severe sepsis and lead

to significant morbidity and mortality if missed 5. Reduction of immunosuppressive drugs to levels that allow better

immunological response to fight the infection process, while still preventing graft rejection.

Kalil AC & Opal SM Curr Infect Dis Rep (2015) 17:32 28

Presenter

Presentation Notes

The neutropenic patient has a primary defect in innate immune responses and is susceptible to conventional and opportunistic pathogens. The solid organ transplant patient has a primary defect in adaptive immunity and is susceptible to a myriad of pathogens that require an effective cellular immune response. Risk for infections in organ transplant recipients is further complicated by mechanical, vascular, and rejection of the transplanted organ itself. The immune suppressed state can modify the cardinal signs of inflammation. Timely diagnostic evaluation and empiric antimicrobial agents can be lifesaving in these patients.

Clinical Implications in Transplantation

• Early identification of sepsis – Assessment of surgical incisions• Adequate source control• Minimize use of urinary catheters and central venous catheters• Adequate control of glucose levels• Consider frequent screening for CMV with adequate treatment• Educate patients and families about the risk of sepsis.

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Sepsis and the Surgical Patient

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Summary of the risk factors associated with post-operative sepsis established through multivariate analysis

Plaeke P et al. Surgery Today 2019. https://doi.org/10.1007/s00595-019-01827-4 32

Incidence of sepsis according to the type of surgery

Plaeke P et al. Surgery Today 2019. https://doi.org/10.1007/s00595-019-01827-4 33

• 2,621 patients; Setting of infection: 31.6% community acquired, 25% early onset hospital-acquired, 43.4% late-onset hospital-acquired.

• Overall mortality 29.1%34

1,594 of 1,982 cultured were culture positiveBlot S et al Intensive Care Med (2019) 45; 1703-1717

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Mortality according to classification of intra-abdominal infection

Blot S et al Intensive Care Med (2019) 45; 1703-171736

Blot S et al Intensive Care Med (2019) 45; 1703-1717

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Presenter

Presentation Notes

Independent risk factors for mortality included late-onset hospital acquired infection, diffuse peritonitis, sepsis, septic shock, older age, malnutrition, liver failure, congestive heart failure, antimicrobial resistance (MRSA, VRE, ESBL producing G- bacteria or CR G-bacteria, and source control failure evidenced by the need for surgical revision or persistent inflammation.

Brakenridge SC et al. Ann Surg 2019; 270:(502-510)

• Prospective, longitudinal cohort study of surgical intensive care unit(SICU) patients with sepsis

• 301 SICU patients with sepsis, 30-day mortality 9.6%• Most had rapid recovery (RAP) 189 (63%); 99 (33%)

developed chronic critical illness (CCI).

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Inpatient Clinical Trajectories and Outcomes

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• ACS-NSQIP database from 2005-2016• Compared a sepsis group to non-sepsis group undergoing the

same procedure• 24,257 patients underwent flap reconstruction surgery, due to

cancer, trauma, etc.40

Sparenberg S. et al. Journal of Plastics and Hand Surgery. 2019. 53(6) 328-334.

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Predictors of sepsis after reconstructive flap surgery

Sparenberg S. et al. Journal of Plastics and Hand Surgery. 2019. 53(6) 328-334.42

Presenter

Presentation Notes

Multivariate logistic regression

Clinical Implications in Surgical Sepsis

• The decrease in early mortality reflects improvement in sepsis screening.1

• The discordance between low inpatient mortality and poor long term outcomes including development of CCI is important information to discuss with complicated surgical sepsis patients and families.

• Clinicians should take a proactive approach - Risk reduction and prevention

• Be aware of risk factors contributing to the development of sepsis in the surgical patient, allowing for early treatment and intervention.

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Summary

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Thank you for your time

55 days until

spring

148 days until

summer

45

Sepsis in Unique Populations - NJHA · L\ukemia accounts for 28% of all cancers diagnosed in...

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