Developing, implementing and scaling up an acute care bundle for intracerebral haemorrhage in Greater Manchester Adrian Parry-Jones NIHR Clinician Scientist & Honorary Consultant Neurologist Manchester Academic Health Sciences Centre Salford Royal NHS Foundation Trust, Salford, UK
Intracerebral haemorrhage • Common health problem ‒ Causes 10-15% of strokes ‒ More common in Asian populations • Poor patient outcomes ‒ Case fatality 30-40% at 1 month ‒ Causes 5.8% of all global deaths ( vs. 6.0% for ischaemic stroke) ‒ Only 20% regain independence ‒ Little improvement in outcomes over last 30 years
Evidence of nihilism in ICH? *Adjusted for sex, age, premorbid mRS, comorbidities of congestive heart failure, hypertension, AF, and diabetes, previous stroke/TIA, Level of consciousness, and ‘out of hours’. † also adjusted for early neurological deterioration (drop in NIHSS 1a of 1 or more in first week). Parry-Jones et al (2016) Int J Stroke 11:321-31
An illustrative case…. • 69 year-old female • Chronic hypertension, atrial fibrillation • DH: Perindopril, warfarin (INR target range 2-3) • Baseline function normal (mRS = 0) • Sudden onset slurred speech and right-sided weakness at 08:00 • Examination on arrival (09:00): • GCS E3 M6 V5 – 14/15 • Severe R-sided weakness • NIHSS 12 • BP 189/110
CT brain at 09:23 - 1.5 h post-onset
Acute management questions…. 1. What should I do about the warfarin treatment? 2. Do I need to do anything about her blood pressure? 3. Should I refer her to the neurosurgeons?
Acute management questions…. 1. What should I do about the warfarin treatment? 2. Do I need to do anything about her blood pressure? 3. Should I refer her to the neurosurgeons?
Anticoagulants – recent Salford audit data 100% 90% % of total ICH admissions 80% 70% 60% 50% 40% 30% 20% 10% 0% Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 2013 2013 2014 2014 2014 2014 2015 2015 2015 2015 2016 2016 2016 No anticoag 32 39 39 39 36 43 59 49 65 72 63 61 28 VKA 2 6 11 6 4 14 3 8 6 11 6 6 1 DOAC 1 0 1 0 1 0 1 1 0 0 7 3 2
VKA- ICH: ‘Time is brain’ Kuramatsu et al. (2015) JAMA 313: 824-36.
VKA-ICH: Improving door-to-needle times Three key changes: 1. PCC stock in the ED 2. Point-of-care INR device 3. Standard protocol to deliver PCC without Haematology referral for every case Parry-Jones (2015) BMJ Qual Improv Rep 8
DOAC-ICH Drug Half life Mode of action Coagulation tests Dabigatran 12-17 h Direct thrombin (II) aPTT, TT Rivaroxaban 7-11 h Factor Xa PT , anti Xa Apixaban 8-15 h Factor Xa anti Xa Edoxaban 10-14 h Factor Xa PT , anti Xa Options for reversal: • PCC (3-factor, 4-factor) • Idarucizumab (for dabigatran) • Andexanet alpha (for Xa inhibitors)
DOAC-ICH: current guidelines What do the guidelines say? • RCP (2016): idarucizumab for dabigatran; 4F PCC for others • AHA/ASA (2015): PCC or rFVIIa ‘might be considered’; Activated charcoal might be used if <2 h since last dose; Haemodialysis for dabigatran. • ESO (2014): No recommendation PCC: • Animal and healthy volunteer data suggests partial reversal • British Committee for Standards in Haematology (2013)
DOAC-ICH: Idarucizumab • Dabigatran antidote, humanised Fab • Dabigatran - 350x higher affinity for idarucizumab than thrombin • Rapid & complete reversal • No prothrombotic effects in volunteers; 1 in 90 pts (RE-VERSE AD) • RE-VERSE AD included 18 ICHs • £2400 per dose (5 g) Pollack et al. N Engl J Med , 2015:373,511 – 20.
Acute management questions…. 1. What should I do about the warfarin treatment? 2. Do I need to do anything about her blood pressure? 3. Should I refer her to the neurosurgeons?
Intensive BP lowering – INTERACT2 • 2839 ICH patients randomised • RCT of acute intensive BP lowering • To a target SBP 130-140 within 1 h • Reduced disability with intensive treatment • Ordinal shift analysis: OR 0.87; 95% CI, 0.77 to 1.00; P = 0.04 • Improved quality of life measures • No effect on survival • No safety concerns Anderson et al.(2013) N Engl J Med. 368:2355-65 .
Intensive BP lowering – ATACH2 • 1000 patients randomised (ICH vol < 60 ml) • Target SBP 110-139 vs 140-179 mmHg, IV nicardipine • Neutral on all outcomes • Increased renal AEs (9.0% vs. 4.0%, p=0.002) INTERACT ATACH Qureshi et al.(2016) N Engl J Med. 375:1033-43 .
Acute management questions…. 1. What should I do about the warfarin treatment? 2. Do I need to do anything about her blood pressure? 3. Should I refer her to the neurosurgeons?
Neurosurgery for ICH • Infratentorial ICH ‒ Risk of brainstem compression, herniation syndromes, hydrocephalus ‒ Procedures – EVD / posterior fossa decompression / haematoma evacuation • Supratentorial ICH – procedures ‒ Early haematoma evacuation in the stable patient ‒ Haematoma evacuation in the deteriorating patient ‒ External ventricular drainage for hydrocephalus
Early haematoma evacuation • IPD meta-analysis – 2186 cases • Overall benefit in cases: GCS 3-8 • Onset to randomisation < 8h • Age 50-70 GCS 9-12 • GCS 9-12 • ICH volume 20-50 ml GCS 13-15 Gregson et al. (2012) Stroke 43: 1496-1504
MISTIE III: MIS and tPA for ICH • Catheter in situ from 1-2 days post onset, for 3-6 days • tPA administered in to haematoma via catheter every 8 h • Phase II trial : • 96 patients (54 surgery, 42 conservative) • 180d mRS ≤ 3: 21% cons vs. 33% MIS (adjusted for p=0.049) Hanley et al. (2016) Lancet Neurol; 15: 1228-37
ABC-ICH project – Improving ICH outcomes Aim: A 10 percentage point reduction in 30 day case-fatality after admission with acute ICH by the end of 2016. How: • Using the Model for Improvement, supported by IS4Ac • Project commenced June 2015 Analysis: • Data collection period: July 2013 to July 2016 • Local ICH registry: case ascertainment via coding and SSNAP • All baseline scans reviewed for location, ICH volume (ABC/2), IVH
Process targets A. Anticoagulant reversal: Deliver PCC < 90 min from arrival B. Blood pressure lowering: Deliver intensive blood pressure lowering with needle-to-target time < 60 min C. Care pathway: Refer patients with good pre-morbid function and any of the following to Neurosurgery • GCS < 9 • Posterior fossa ICH • Obstructed 3 rd /4 th ventricle • Haematoma volume > 30 ml
Anticoagulant reversal – DNT for PCC DNT (min) 500 450 400 350 300 250 200 150 100 50 0 May 14 Oct 14 Nov 14 Jan 15 Jun 15 Sep 15 Nov 15 Jan 16 Feb 16 Apr 16 May 16 Education and QI project commenced Ref sheet POC INR awareness work
Intensive BP lowering – NTT time NTT (min) 1000 800 600 400 200 0 Jun 14 Nov 14 Mar 15 Apr 15 May 15 Jul 15 Aug 15 Sep 15 Oct 15 Nov 15 Dec 15 Jan 16 Feb 16 Mar 16 Apr 16 May 16 Jul 16 Protocol introduced Stay in ED until target reached Change to GTN first
% all ICH admissions 10% 20% 30% 40% 50% 60% 70% 0% May 14 Jun 14 Jul 14 Reduction in DNR orders at < 24 h Aug 14 Sep 14 Oct 14 Nov 14 Dec 14 Jan 15 Feb 15 Mar 15 QI project commenced Apr 15 May 15 Jun 15 Jul 15 Aug 15 Sep 15 Oct 15 Nov 15 Dec 15 Jan 16 Feb 16 Mar 16 Apr 16 May 16 Jun 16 Jul 16
% all ICH admissions 10% 20% 30% 40% 50% 60% 0% May 14 LCL Jun 14 Jul 14 Aug 14 Admissions to critical care Sep 14 Oct 14 Nov 14 Dec 14 Jan 15 Feb 15 Mar 15 QI project commenced Apr 15 May 15 Jun 15 Jul 15 Aug 15 Sep 15 Oct 15 Nov 15 Dec 15 Jan 16 Feb 16 Mar 16 Apr 16 May 16 Jun 16 Jul 16
Analysis of mortality – Baseline characteristics Factor Pre QI (n=363) Post QI (n=316) p Age 72.0 (57.1 – 81.1) 69.6 (55.2 – 80.1) 0.34 Premorbid mRS (0-2) 289 (79.6%) 260 (82.3%) 0.15 Anticoagulant 54 (14.9%) 41 (13.0%) 0.51 Sex (female) 172 (47.4%) 163 (51.6%) 0.28 GCS 14 (10-15) 14 (10-15) 0.60 Infratentorial 42 (11.6%) 40 (12.7%) 0.66 IVH 141 (38.8%) 127 (40.2%) 0.61 ICH volume (ml) 20.0 (6.5 – 54.1) 15.8 (5.0 – 45.2) 0.055 Pre QI: Jul 2013 – May 2015; post QI: Jun 2015 – Jul 2016. Excluded 33 cases not under stroke or neurosurgery (14 pre, 19 post)
QI project – unadjusted analysis of survival Pre-QI: • Jul 2013 – May 2015 • 363 cases admitted • 30-day case fatality = 35.3% Post-QI: • Jun 2015 – Jul 2016 • 316 cases admitted • 30-day case fatality = 25.3% Logrank test: p=0.002
QI project – Cox regression analysis Factor HR 95% CI Sig. GCS 0.85 0.83 to 0.88 <0.0001 Anticoagulant 1.27 0.94 to 1.73 0.124 Infratentorial 1.79 1.29 to 2.49 0.001 IVH 1.44 1.12 to 1.86 0.04 ICH vol 1.006 1.004 to 1.008 <0.0001 Age 1.053 1.043 to 1.063 <0.0001 Post QI 0.70 0.54 to 0.90 0.006 Post QI (unadj) 0.68 0.52 to 0.86 0.002
Mortality analysis – vs. rest of England & Wales Mean 30d p mortality Jul 13 – May 15 Rest of SSNAP 29.0% Salford 35.3% Difference 6.2% <0.0001 Jun 15 – Jul 16 Rest of SSNAP 27.0% Salford 25.3% Difference -1.8% <0.0001 Difference in -8.1% <0.0001 Difference
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