This document summarizes several landmark clinical trials that have impacted emergency medicine practice. It discusses trials regarding the use of tPA for acute ischemic stroke (NINDS, ECASS III), early goal-directed therapy for sepsis (Rivers, Surviving Sepsis), clinical decision rules for cervical spine imaging (NEXUS, Canadian C-Spine Rule), fluid resuscitation (SAFE Trial), use of steroids for Bell's Palsy (Sullivan et al, Berg et al), and CT sensitivity within 6 hours of headache onset for subarachnoid hemorrhage (Perry/Steill et al). Assessment scales for functional outcomes in various conditions are also outlined.

1. Dr Dane Horsfall FACEM
Cabrini Hospital

2.  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

3.  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

4.  National Institute of Neurological Disorders
and Stroke-Washington DC
 “t-PA for acute ischemic stroke”
 Randomized, Double Blinded, recombt-PA
(Alteplase)
 tPA 0.9mg/kg(max 90mg) 10% bolus then inf
1/24
 Recommended tPA< 3/24

5.  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

6.  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)

7.  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% vsPlac 45% - NNT 14
◦ 2-6 disability
 ICH(symp) t-PA 2.4% vsPlac 0.2% - NNH 45
 Mortality t-PA 7.7% vsPlac 8.4% no difference
 BUT studies showing no Difference:
◦ ECASS I 1995 620pts tPA< 6/24
◦ ECASS II 1998 300pts 0-6hrs

8.  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

9.  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 <vasopressorsNoradrenaline
◦ 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

11.  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

12.  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

13. BIBA at 0430 - fever and severe R leg pain since 0100
PHx
CLL/Neutropenia - treated with gCSF
0435-
Temp 400C
BP 87/62 mmHg
HR 160/min irregular (AF)
RR 17/min
O2 sat 95% (air)
Right leg red / swollen to thigh “Cellulitis”

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

15.  Persistent hypotension, SBP 70-90/DBP 50-60
 Remained in AF
 Pain very difficult to control
 Temp 38.4
 0720-Hypotension persists 80/50
Rx-Gelofusine 500 and further 1000 ml N/Saline
(Filling✔)

16.  0845 IDC
 0900 IV Metaraminol increments
 0930 IV Gelofusine then IV Albumin
 1000 CVC (1000, IJV) CVP 28-30-well filled ✔
 1035 Noradrenalineinf -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

17.  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

18.  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?

19.  Advantages
◦ Mechanism
◦ Age >65
 Disadvantages
◦ Complicated
◦ No distracting injury*

21.  A comparison of Albumin and Saline for fluid
resus in ICU (Saline vsAlbumin Fluid
Evaluation)
 Multicentre, randomised, double blinded,
7000pts 4% Alb vs N/Saline 28/7- no
difference in mortality
 Conclusion- Use N/Saline

22.  “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)

23.  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

24.  “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 abNNeuro-?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

25.  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

26.  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

27.  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