Practice Changing ED Research

Dr Dane Horsfall FACEMCabrini Hospital

Literature extensive Listen to this talk! Journal watch-http://emergency-medicine.jwatch.org/

EM:RAP-http://www.emrap.org/

Landmark Trials -Trials that affect our practice

How to approach Literature

NINDS 1995/ECASS III 2008 Rivers 2001/Surviving Sepsis 2008 + Case USA vs Canada: NEXUS 2001/Canadian

Cervical Spine 2001 SAFE 2004 Sullivan 2007 Perry/Steill SAH 2011

The Good Stuff…

National Institute of Neurological Disorders and Stroke-Washington DC

“t-PA for acute ischemic stroke” Randomized, Double Blinded, recomb t-PA

(Alteplase) tPA 0.9mg/kg(max 90mg) 10% bolus then

inf 1/24 Recommended tPA < 3/24

NINDS 1995

NIHSS-National Institutes of Health Stroke Scale◦ neuro deficit, 42-point scale, neurologic deficits in 11 categories.

Eg mild facial paralysis = 1, complete right hemiplegia/aphasia =25.

Barthel Index◦ perform activities of daily living (eating, bathing, walking, toilet)

out of 100 Modified Rankin Scale-overall assessment of function

◦ 0= asymptomatic up to 5 =severe disability Glasgow Outcome Scale-global assessment of function

◦ 1=good recovery, ◦ 2=moderate disability ◦ 3=severe disability◦ 4=vegetative state◦ 5=death

NINDS 1995 Scales

Part 1 291pts NIHSS score at 24hrs= no difference

Part 2 333pts Combination score at 3/12 Results combined for analysis t-PA minimal/no disability scores- 12% absolute

increase, 32% relative, in, NNT=8 t-PA Increase ICH by 6% NNH=17

◦ Assoc with more severe isch strokes/more oedema on CT Mortality t-PA 17%, Placebo 21% (Not stat.

significant)

NINDS 1995

European Cooperative Acute Stroke Study “Thrombolysis with Alteplase 3 to 4.5 Hrs after

Acute Ischemic Stroke” 821pts tPA 3-4.5 hrs 90 day disability –modified Rankin Scale

◦ 0-1 no disability t-PA 52% vs Plac 45% - NNT 14◦ 2-6 disability

ICH(symp) t-PA 2.4% vs Plac 0.2% - NNH 45 Mortality t-PA 7.7% vs Plac 8.4% no difference BUT studies showing no Difference:

◦ ECASS I 1995 620pts tPA < 6/24◦ ECASS II 1998 300pts 0-6hrs

ECASS III 2008

Contraindications:◦ Bleeding risk

Anticoagulants, Platelets <100 Massive CVA > 1/3 cerebral hemisphere-obtund/complete

hemiplegia Uncontrolled HT >185/110 CVA/Head Injury in last 3/12 or ICH at an time Bleed in last 3/52, bleeding diathesis, arterial puncture last 7/7 Pregnancy Trauma/Surgery in last 14/7

◦ Not Stroke: Seizures Hypoglycaemia

◦ No significant improvement possible Resolving stroke Previous disability

Alfred/Cabrini Protocol- t-PA for Ischaemic Strokes < 4.5 hrs

263 pts Rx in ED for 6/24 prior to ICU: ◦ 130 EGDT◦ 133 standard Rx◦ In hospital Mortality EGDT 30%, Standard 46%◦ NNT 6

EGDT: ◦ CVP 8-12mmHg if < Fill 500ml bolus N/S every

30 mins◦ MAP >65mmHg if < vasopressors Noradrenaline◦ ScvO2 (central mixed venous O2 sat) >70%

if < Tx RBC to Hct > 30% if ScvO2 still < inotropes(dobutamine) Central venous Sats >70% surrogate marker of adequate

tissue perfusion-ie adequate resus from septic shock

Rivers 2001 - Early Goal Directed Therapy in Sepsis

Funded by manufacturer of CVC High control mortality Dr Rivers managing pts in ED Continuous Scv O2sats not practical to

measure Cant argue against concept

Rivers – Criticisms:

EGDT Antibiotic within 1 hr Source Control crystalloid or colloid fluid resuscitation Vasopressor = Noradrenaline Dobutamine if CO low post

filling/vasopressors Stress-dose steroid only if BP poorly

responsive to vasopressors

Surviving Sepsis 2008

BIBA at 0430 - fever and severe R leg pain since 0100

PHxCLL/Neutropenia - treated with gCSF

0435-Temp 400CBP 87/62 mmHgHR 160/min irregular (AF)RR 17/minO2 sat 95% (air)

Right leg red / swollen to thigh “Cellulitis”

ED Case 85 yo M

Two peripheral IVs, IV Tazocin 4.5g (early broad spectrum antis )✔IV fluid N/saline 1000mls (filling )✔IV analgesia Morphine incrementsIV Digoxin 500 mcg

0510 Initial empiric treatment

Persistent hypotension, SBP 70-90/DBP 50-60 Remained in AF Pain very difficult to control Temp 38.4

0720-Hypotension persists 80/50Rx-Gelofusine 500 and further 1000 ml N/Saline (Filling✔)

0620 Course

0845 IDC 0900 IV Metaraminol increments 0930 IV Gelofusine then IV Albumin 1000 CVC (1000, IJV) CVP 28-30-well filled ✔ 1035 Noradrenaline inf -Vasopressor ✔ 1200 IV Vancomycin 1g 1220 Transfer ICU

Non EGDT-central venous sats, Survivng sepsis-Source control

Outcome ◦ Clinical Dx Necrotizing Fasciitis by ID, pt palliated

deceased later that day in ICU

0830 – 1220 in ED ICU Reg Mx

National Emergency X-ray Utilization Study (Jerry Hoffman UCLA)

34,000pts, 21 sites, prospective observation of decision tool: Sens >99% Spec 12%

If none of 5 clinical signs=clear Cx spine◦ Midline tenderness◦ Distracting injury◦ Altered GCS◦ Neurology◦ Intoxication

NEXUS - 2000

9000pts normal conscious state** Sens 100%, spec 45% 1. High risk factors

◦ age>65 ◦ Mechanism (fall>1m,axial,MCA >100km/hr, motorbike,

bicycle)◦ Neuro*

2. Low Risk factors◦ low speed MCA◦ sitting/ walking◦ no midline tenderness*/delayed pain

3. Able to Laterally neck rotation 45 degrees?

Canadian Cervical Spine Rules - 2001

Advantages◦ Mechanism◦ Age >65

Disadvantages◦ Complicated◦ No distracting injury*

Canadian Cervical Spine

A comparison of Albumin and Saline for fluid resus in ICU (Saline vs Albumin Fluid Evaluation)

Multicentre, randomised, double blinded, 7000pts 4% Alb vs N/Saline 28/7- no difference in mortality

Conclusion- Use N/Saline

SAFE 2004

“Early treatment with prednisolone or acyclovir in Bell's palsy”

Double-blind, placebo-control, randomized trial 500 Pts with Bells (no Herpes vesicles) < 72 hrs

onset 10/7 Rx with:

◦ Pred 25mg bd◦ Acyclovir◦ Both◦ Placebo

Rating facial paralysis at 3 and 9/12 with “House-Brackmann scale” (1 normal to 6 total paralysis)

Sullivan 2007

Recovery at 3/12◦ Pred 83% vs no Pred 64%◦ Acyclovir 71% vs no Acyclovir 75%◦ Both 80%

Recovery at 9/12◦ Pred 94% vs no Pred 82%◦ Acyclovir 85% vs no Acyclovir 91%◦ Both 93%

Conclusion-Give Prednisolone!!! Supported by results from: T Berg et al “The Effect of

Prednisolone on Sequelae in Bell's Palsy” Arch Otolaryngololgy - Head Neck Surg. 2012;138(5):445-449 May 2012

Sullivan 2007

“Sensitivity of CT < 6/24 H/A onset for Dx SAH: prospective cohort study”

3100 pts, 11 Hospitals, 2000-2009 Adults, New acute h/a, no abN Neuro-?SAH 240 SAH (8%) Overall CT(3rd Gen) 93% sensitive,

100%specific Subgroup 950pts CT < 6/24 100%

sens/specific (Dx all 121 SAH) ie Normal CT <6/24 rules oot SAH

Perry/Stiell 2011

Urgent CT (Cabrini CT ?3rd Gen) ?to LP or not to LP – depends on case and

discussion with patient Perry study not validated in Australia-

unlikely to be repeated Some ED’s have changed protocols

What to do?

NINDS - “t-PA for acute ischemic stroke”, N Engl J Med 1995;333:1581-7

ECASS III – “Thrombolysis with Alteplase 3 to 4.5 Hours after Acute Ischemic Stroke” N Eng J Med 2008;359:1317

Rivers et al – “Early goal-directed therapy in the treatment of severe sepsis and septic shock”, N Engl J Med, 345(19):1368-77, 2001 Nov 8.

Surviving Sepsis–Dellinger RP et al. January 2008 "Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock: 2008". Intensive Care Med 34 (1): 17–60.

NEXUS – J Hoffman and The National Emergency X-Ray Utilization Study Group – “Validity of a set of clinical criteria to rule out injury to the cervical spine in patients with blunt trauma”, N Engl J Med 2000;343:94-9

References 1

Stiell IG et al, “The Canadian C-spine rule for radiography in alert and stable trauma Patients”, JAMA. 2001 Oct 17;286(15):1841-8

SAFE – “A Comparison of Albumin and Saline for Fluid Resuscitation in the ICU”, N Engl J Med 2004;350: 2247-56.

Sullivan et al – “Early treatment with prednisolone or acyclovir in Bell's palsy”, N Engl J Med. 2007 Oct 18;357(16):1598-607

“The Effect of Prednisolone on Sequelae in Bell's Palsy” Arch Otolaryngology Head Neck Surg. 2012;138(5):445-449 May 2012

Perry/Steill et al – “Sensitivity of CT performed within six hours of onset of headache for diagnosis of SAH: prospective cohort study” , BMJ 2011 July18;343:d4277

References 2