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.
2. Literature extensive
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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
10.
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*
20.
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