Clinical aspects of infections in burns patients Elizabeth Chipp

Transcription

1 Clinical aspects of infections in burns patients Elizabeth Chipp Consultant Plastic and Burns Surgeon University Hospital Birmingham Birmingham Childrens Hospital

2 Birmingham London 2

3 Birmingham Burn Centers 600 / Year. Average 8% TBSA. 17 Adults beds, 9 Paediatrics. Area covered 5 million population (13m major burns) 7 Consultant Surgeons, 5 registrars, 4 Senior House Officers 3

4 Birmingham Burns Research Scar Free Burns Research Centre. NIHR Trauma Research Centre Royal Centre For Defense Medicine. 4

5 Queen Elizabeth Hospital 5

6 Birmingham Children s Hospital 6

7 University of Birmingham 7

8 Queen Elizabeth Hospital Institute of Biomedical Research Medical School Institute of Translation Medicine 8

9 Burn Sepsis Compared to critical Care and Trauma 1 : Higher incidence: 8-42% Higher Mortality: 28-65% Cost $16 Billion/year US 2 1 Mann et al. Comparison of mortality associated with sepsis in the burn trauma and general intensive care unit patient: a systematic review of the literature Shock 2 Angus DC et al :Epidemiology of severe sepsis in the United States: analysis of incidence,outcome, and associated costs of care. Crit Care Med 29(7):1303Y1310, 2001.

10 Commonest Causes Burn Wound Infection Ventilation Associated Pneumonia IV site infection Urinary Catheter Infection

11 How to Prevent and Manage? Early wound excision Adherence to guidelines bundles Strict Infection Control Policies Antibiotic Stewardship

12 Challenges Diagnosis Delay in starting antibiotic reduces survival 7.6% for every hour of delay Kumar A, Roberts D, Wood KE, Light B, Parrillo JE, Sharma S, et al. Duration of hypotension before initiation of effective antimicrobial therapy is the critical determinant of survival in human septic shock. Critical care medicine. 2006;34(6):

13 Challenges Diagnosis Sepsis SIRS

14 Challenges Diagnosis ABA 2007 Consensus conference trigger criteria PLUS A. Positive culture B. Pathological tissue source identified C. Clinical response to anti-microbials Score of 3 + A, B or C = sepsis Greenhalgh DG, et al.;. J Burn Care Res 2007;28:

15 Challenges Diagnosis Bio-markers Predictive Value Procalcitonin: 0.82

16 Challenges Diagnosis Early Diagnosis of Sepsis?

17 Scientific Investigation of Biological pathways Following Thermal Injury (SIFTI) Study 5 year Programme Prospective cohort observational study 150 patients, Multi-centre

18 Hampson P et al. Neutrophil Dysfunction, Immature Granulocytes, and Cell-free DNA are Early Biomarkers of Sepsis in Burninjured Patients: A Prospective Observational Cohort Study. Ann Surg 2017;265: Neutrophil Dysfuntion 1. Phagocytic Index 2. immature granulocytes 3. cell-free mdna

19 1. Phagocytic index Mann-Whitney test; *p<0.05 Burn patients Vs Healthy controls

20 2. Immature granulocytes IGs Total Neutrophil count Neutrophil; Giemsa stain Arrows: Immature Granulocytes IG Mann-Whitney test; *p<0.05 (Ann Surg 2017;265: )

21 2. Immature granulocytes IGs Total Neutrophil number Immature granulocytes number linear mixed-effects models: Line represents predicted mean fixed effects, shaded area represents 95% confidence intervals. (Ann Surg 2017;265: )

22 3. Cell-Free DNA (cf DNA) Nuclear cf DNA Mann-Whitney test; *p<0.05

23 Phagocytic Index immature granulocytes Nuclear cf DNA are possible biomarker for early sepsis (Ann Surg 2017;265: )

24 Day 1 Biomarkers for sepsis Variable Day 1 Number of Patients Number of Septic Patients AUROC (95% CI) IG count + cfdna (0.684, 0.973) cfdna + PI (0.700, 0.934) IG count + PI (0.817, 1.000) cfdna + PI + IG count (0.854, 1.000) (Ann Surg 2017;265: )

25 Day 1 Biomarkers for sepsis Revised Baux Score: Burn size + age + 17 (Inhalation injury) Osler T, Glance LG, Hosmer DW. Simplified estimates of the probability of death after burn injuries: extending and updating the baux score. The Journal of trauma. 2010;68(3): a single-term logistic regression model developed using data on 39,888 burned patients provided by the US national burn repository

26 Day 1 Biomarkers for sepsis Model Two predictors: Number of Patients Number of Septic Patients AUROC (95% CI) IG + rbaux (0.766, 1.000) PI + rbaux (0.883, 1.000) cfdna + rbaux (0.886, 1.000) Three predictors: IG + PI + rbaux (0.955, 1.000) PI + cfdna + rbaux (0.948, 1.000) IG + cfdna + rbaux (0.863, 1.000) (Ann Surg 2017;265: )

27 Conclusions 1. Burn-injury is associated: Reduced Phagocytic Index PI Increased circulating immature granulocyte (IG) Increased circulating cell-free DNA (cfdna), 2. PI, IG and cf ndna are promising early biomarkers sepsis. 3. Laboratory and clinical indicators On Day One can improve sepsis prediction accuracy of 99%

28 Challenges Better Wound Dressings Anti- Microbial Dressings (AMDs) Why we need them? active agents Systemic antibiotic are not appropriate Reduce Colonisation &? Prevent infection. Silver (Ag) Honey Chlorhexidine Iodine Seaweed One in seven dressings contain silver UK: 25 million on silver in 2006/7

29 Challenges Better Wound Dressings Silver Dressings Cochrane review* Systematic review** 26 RCTs Wound infection and healing: insufficient evidence. SSD poor quality RCT suggesting êhealing 14 RCTs No better or worse than control * Storm-Versloot MN, Vos CG, Ubbink DT, Vermeulen H. Topical silver for preventing wound infection. The Cochrane database of systematic reviews. 2010(3):Cd ** Aziz Z, Abu SF, Chong NJ. A systematic review of silver-containing dressings and topical silver agents (used with dressings) for burn wounds. Burns. 2012;38(3):

30 Challenges Better Wound Dressings Acetic Acid medical History* Hippocrates ( BC) Plague in London 1665/6 American Civil war WWI Currently: sporadic usage * Phillips I, Lobo AZ, Fernandes R, Gundara NS. Acetic acid in the treatment of superficial wounds infected by Pseudomonas aeruginosa. Lancet 1968;291:11e13

31 Acetic acid Biofilms biomass (OD) ACI_721 ACI_AYE Acticoat L-Mesitran Net 5% AA 2.5% AA 1.25% AA 0.63% AA 0.31% AA 0.16% AA Agent tested 0.08% AA 0.04% AA 0.02% AA 0.01% AA Positive control Negative control Journal of Hospital Infection. 2013;84(4):329-31

32 Acetic acid Journal of Hospital Infection. 2013;84(4):329-31

33 Acetic acid Silver group: Mepilex Ag and Acticoat: % reduction in biofilm biomass. Statistically significant. Aquacel dressings: ~40% reductions with Pseudomonas isolates, ~70% with the Acis UrgoTul silver and PolyMem Silver : reductions and increases noted. Non-silver dressings: Inadine : ineffective L-Mesitran : largely ineffective AA: reductions of 90% from 5% down to 0.16%

34 Acetic acid AA is stable at 24h when in contact with dressing gauze and organic material up to 24h. AA effective: 0.16 dilution

35 Summary Burns infection and sepsis difficult to define and diagnose early Major cause of morbidity and mortality Efforts to identify biomarkers of early sepsis Translational research Dressings may aid with treatment of localised infection

36 Acknowledgments UoB Division of Immunity & Infection Prof. Janet Lord Dr Paul Harrison Dr Peter Hampson Robert Dinsdale Dr Chris Wearn Dr Jon Hazeldine Hema Chahal Dr Jon Bishop QEHB Burns Centre Karen Piper Amy Bamford (Burns Research Nurse) Birmingham Children's Hospital Miss Yvonne Wilson Miss Federica D Asta Clare Thomas (Lead Nurse) Queen Victoria Hospital East Grinstead Mr Baljit Dheansa Simon Booth (Burns Research Nurse) St Andrews Burns Centre Chelmsford Professor Peter Dziewulski Helen Gerrish, Natalie Whybro (Burns Research Nurses)