Advances in the Management of Empyema

Transcription

1 Advances in the Management of Empyema RCP Update in Respiratory Medicine 26 th January 2017 Najib M Rahman Associate Professor of Respiratory Medicine University of Oxford najib.rahman@ndm.ox.ac.uk

2 Financial disclosures Drugs and matched placebos for clinical trials: Roche / Genentech / Boehringer / Lunamed / Syner-Med Technical equipment for trials: Rocket Medical UK/ GE Medical Trials unit funding: Roche / Syner-Med / GSK Clinical advice consultancy: IP: Rocket Medical Lipoteichoic acid for pleurodesis Research funding: NIHR / HTA trials / MRC / UKCRN / CRUK / BLF / UKNRCI

3 Infection Ancient History: A diseased wound in the breast * An abscess with prominent head from the breast ǂ Descriptions emphasise the need to ensure drainage of infected fluid *From the Edwin Smith papyrus, c1500 BC (trans. Breasted JH, 1930) ǂ Attributed to Egyptian physician Imhotep, c3000 BC

4 Guillaume Dupuytren ( ) I would rather die at the hand of God than at the hand of a surgeon

5 Sir William Osler ( ) Empyema needs the cold steel of a surgeon rather than some fool of a physician. Died at the hand of surgeon

6 Burden Pneumonia: Combined (UK + USA) ~ 1.5 million cases of pneumonia per year Related Effusion: Estimated 30-40% develop parapneumonic effusions ~ 600,000 cases per year Total number of complicated PPEs / empyema = 80,000 cases per year i.e. around 10% of parapneumonic effusions are complicated or frankly infected

7 Infection Rx principles 1. Accurate diagnosis 1. Control sepsis: Suitable antibiotic therapy 2. Drainage of infected material: Intercostal tube drainage Intrapleural adjunctive therapies Surgery

8 Infection Outcomes High morbidity: Mean hospital stay days Surgical rate up to 35% >20% one year mortality: Unchanged over last 20 years 7% in MI 8% in hospitalised pneumonia Baigent et al BMJ; 316: Neill et al Thorax; 51:

9 Case 24 year old woman Normally fit and well 4/52 history: Flu like illness lasting 3 days Initial recovery 7 days later, breathlessness / cough / fever Rx with oral antibiotics for 3/7 Last 2 weeks: Night sweats / fevers / left sided chest pain

10 Examination Low grade pyrexia (37.8 O C) RR = 20 Saturations 94% room air BP 117 / 73 P=98 L basal bronchial breathing and dull PN

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12 Investigation / Rx Commenced antibiotics amoxicillin + macrolide CURB65 = 1 IV fluid Blind pleural aspiration: 5mls straw coloured pleural fluid Microbiology sample sent Sent to lab for biochemical analysis: ph = 7.43

13 What is the next best step? 1) Continue current treatment 2) CT chest 3) Change to intravenous penicillin and gentamicin 4) Refer to thoracic surgery 5) Re-aspirate under guidance

14 Progress Fluid not drained on the basis of pleural ph 24 hours later: More unwell Spiking fevers fluid and blood cultures negative team involved Bedside thoracic ultrasound

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17 fluid ph Use: Highly sensitive measure of poor clinical outcome Clinically used as aid to decide which patients to drain Not 100% sensitive AJRCCM; 152:

18 When to question ph 1. Not in keeping with clinical picture 2. Multiloculation 1 3. Variants in measurement 2 : Contaminant Delay Air not excluded from syringe Not blood gas analyser 1 Chest : AJRCCM :483

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22 Frank Pus

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24 Which of the following should now be conducted? 1. Small bore chest tube 2. Large bore chest tube 3. VATs 4. Thoracotomy 5. Other

25 Chest tube size and outcome Multiple case series: Radiologically guided small bore chest tubes Good outcomes Strongly held clinical belief remains Bigger is better Single direct comparison (paediatric)

26 Chest tube size Smaller tubes not associated with increased mortality or surgical requirement Purulence Effect independent of purulence of fluid Chest 2010;137;

27 n=128 Rahman et al, Chest 2009

28 Which antibiotics should be used? 1. Meropenem and Vancomycin 2. Penicillin and Gentamicin 3. Cefuroxime and clariyhromycin 4. Co-amoxiclav and metronidazole 5. Await culture results

29 Which organism is the most likely? 1. Haemophilus Influenza 2. Strep. Milleri group 3. Strep. Pnuemonia 4. Staph. Aureus 5. Mycoplasma Pneumoniae

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31 Community Hospital

32 Microbiological diagnosis Yield: 40% microbiologically negative throughout treatment Empirical therapy therefore required in large minority Increasing diagnostic yield: Increase yield using Blood Culture Bottle Media? Supportive evidence from PD patients Menzies et al, Thorax 2011: Direct comparison Usual culture only vs addition of BCB innoculation (Bactec system)

33 Menzies et al 2011 Use of Bactec system in addition to normal culture: Increases diagnostic yield by 21% Directly alters antibiotic management in 4% No false positive samples All fluid volumes (2 / 5 / 10mls) equivalent Blood culture system alone results in some false negatives

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35 Microbiological diagnosis Increasing yield: Today: Innoculate pleural fluid in to Blood Culture Bottles in addition to standard culture Tomorrow?: Molecular microbiological techniques

36 Wrightson and Wray et al, in submission

37 What factors are shown to predict poor outcome in this patient? 1. Septation on US 2. Loculation on CT 3. Bacteriological cause 4. Purulence of pleural fluid 5. Baseline urea (7.8)

38 Outcome prediction in pleural infection MIST1 + MIST2 cohorts: Identical recruitment criteria Multivariate modelling Identify factors which predict outcome which are: Clinically accessible at baseline Biologically plausible

39 Outcome prediction in pleural infection RAPID score Parameter Measure Score Renal Urea <5mmol/L 5-8 mmol/l >8 mmol/l Age Age <50 years years >70 years Purulence of fluid Infection Source Purulent Non-purulent Community acquired Hospital acquired Dietary Factors Albumin > or = 27mmol/L <27mmol/L 0 1 Risk categories Score 0-2 Score 2-4 Score 5-7 Low risk Medium-Risk High Risk

40 Kaplan-Meier Survival Estimates by RAPID score Low Medium Low Medium High High Rahman & Maskell, Chest 2014

41 Outcome prediction - conclusions No established criteria on which to base decisions on response to treatment currently Therefore no way of reliably predicting who will fail medical management Treatment trial of medical therapy is reasonable

42 Progress 12F drain inserted under ultrasound guidance 600mls fluid drained over 2 days fluid culture: Standard negative Culture Bottle resistant E.coli Switched to iv tazocin

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44 Progress Poorly draining chest tube:? malposition Removed second placed more caudally Despite this 100mls drained over 2 days Further fevers Inflammatory markers not changed

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46 What is the next treatment step? 1. Insert a larger bore tube 2. Medical thoracoscopy 3. Thoracotomy 4. VATs 5. Intrapleural tpa and DNase

47 Patient unwilling to undergo surgery Underwent an intervention

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49 3 days post

50 Progress Discharged 3 days post intervention Review one month later: CXR normal Lung function normal No signs of sepsis

51 Intervention received MIST2 regimen Intrapleural tpa 10mg bd Intrapleural DNase 5mg bd 3 days Rx

52 MIST2 Purulent pleural fluid Acidic, ph<7.2 Bacteria positive DNase TPA DNase & TPA Placebo Radiograph outcome Surgical Rate / Mortality NEJM; 365:

53 Primary Outcome Day 1 Day Absolute change = (day 7 day 1) = = -30.9% Relative change = (day 7 day 1) / day 1 = -30.9/38.9 = -79.4%

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55 Secondary Outcomes

56 Further evidence Picolo et al, Ann Am Thor Soc centres, n=107 All failing medical therapy All given MIST2 regimen 92.3% success rate Conclude: Safe and effective as rescue therapy

57 Immediate surgery for all? Wait et al. Chest 1997; 111: : High 20 tube randomised, failure rate 9 to in D+SK, medical 11 arm to VATS No Shorter blindingdrainage period and hospital stay No objective decision criteria Bilgin et al. ANZ J Surg 2006; 76:120-2: Primary 70 randomised outcome not to VATs specified versus tube drainage In VATs group: No blinding Shorter hospital stay Lower thoracotomy requirement (17% versus 37%) No objective decision criteria

58 Messages 1. ph: Potential pitfalls with pleural ph Caution with multiloculated effusion Value of direct US guided procedure Accurate measurement required 2. Fluid Culture: Increase yield using BCB system Easy and readily available

59 Messages 3. Tube size in pleural infection: Smaller tubes probably as good as larger 4. Potential outcome predictors: RAPID criteria? US in the future

60 Messages 5. New treatment directions: MIST2 regimen improves chest radiograph MAY reduce surgery and hospital stay Good option if surgery not accepted / offered Caution with liberal use