Life threatening asthma presentation at the RSM 9/11/16 by Dr Sellers - IM / IV drugs

1. At school: playing football: at home:
out of hospital (late Ambulance):
in Syria:

2. Asphyxial Death
Goblet cell secretion> 150 milli-sec
How may we predict death / life threat ?

3. Adrenaline IM auto-injectors in all educational
establishments
for asthma and anaphylaxis - Good Samaritan clause
November 2013

4. Nothing to lose
Two or three may be needed, through clothes into thigh
0.5 mg adrenaline for everyone
Paramedics will use same dose IM
Demonstration during breaks
Petition 163589
Rule 28: If a Coroner concludes there is a potential for the same cause of
death to occur again and that this is preventable, he/she is empowered to
draw public attention to this

5. Jext, Epipen, Emerade in UK. Anapen in EU.
Auvi Q in USA, gas powered, speaking - withdrawn

7. Assessing Severity – Parents, staff
Tesco party blow-out
Kazoo
Do-Re-Mi-Fa-So-La-Te-Do
Can’t speak

8. Sign 153: British guideline on the management of
asthma Sep 2016
9:3:12 In patients with acute severe or life-threatening asthma,
anaesthetists and intensivists should be notified as soon as possible
if there is no improvement in or deterioration of asthma.
Who makes this decision and when?
Pneumothorax?

12. Treat IV
IV MgSO4 40mg.kg-1 over 4 minutes (5g /10ml ampoule)
then
IV Salbutamol 5mcg.kg-1 bolus, repeated (500mcg /1ml ampoule)
or
15mcg.kg-1 over 10 minutes (Guide)
25kg: 1g Mg; 125mcg salb bolus, or 375mcg 10 min infusion
Allows cough to remove plugs

13. Smooth muscle relaxation
MgSO4 , beta2-agonists, and inhaled anaesthetics
activate adenyl cyclase,
increases cAMP, inhibits calcium entry.
Phosphodiesterase inhibitors stop cAMP breakdown
(amino, enoximone, viagra)

14. Safety of IV MgSO4
Eclampsia
4g bolus, and/or 4 to 6g over 15 minutes
Supra Ventricular Tachycardia (reversion)
2g over 5 seconds (!!) (Wesley 1989)
2g over 15 seconds (Viskin 1992)
2g over 60 seconds (Iseri 1985, Hays 1994)
Side effects - Flushing, Warmth, Nausea
Asthma
1.2 – 2g over 20 minutes. 3Mg 2012, Shan 2013; little effect
= sub-therapeutic levels. No evidence why 20 min; o’dose?.

15. Safety of IV MgSO4
Atrial suppressant effects attenuates
or removes the beta1–agonist tachycardia effect
of subsequent IV adrenaline and IV salbutamol
Sellers et al. Br J Anaes 2010 case reports (x7, me)
Edwin and Panikkar 2011, Barker and Chin 2103
Not in 2016 guide
Case reports (x7) using sevoflurane during ventilation are.

16. What stops IV salbutamol use?
Cochrane 2003 15 RCTs ER nebs vs iv beta2s/amino
Swedish 1990: IPPB 5mg x 4, vs iv 350 mcg in 10 min
IPPB better, but tachycardia
Salmeron 1994: Neb 5mg x 2 vs iv 500 mcg in 60 min
14 hr asthma before trial. Nebs better. No IV loading dose
Browne 1997: Neb 5mg continued; iv NaCl vs 15 mcg.kg in 10
min (children)
IV group 8 hr faster discharge ER

17. IV 50 kg dose over 10 mins
and serum levels
Swedish: 350mcg : 7 ng.ml @ 55 min
Salmeron: 83mcg then infusion : (pre 3.6) 10 ng.ml @ 60 min
Browne: 750mcg : estimate 20-40 ng.ml

18. Safety of IV salbutamol (terbutaline)
Tachycardia (Mg stops it)
K+ down
Tremor
Lactic acidosis after long-term inhaled and IV
(of dubious clinical significance)
IV aminophylline
No benefit in acute asthma, but someone will want to give it

19. What is used in A&E?
Australia / NZ – Franz Babl: Arch Dis Child 2008
What would you give in a critical asthma scenario?
IV Salb 89%, Mg 55%, Amino 45% (2nd or 3rd )
UK / NI – Morris et al: Thorax 2014. 10 weeks
110 children received IV
Salb 61, Mg 67, Amino 52
Commonest order: Salb, Mg, Amino
30 different IV regimes – of dose, rate, duration, and order
Fast resolution of spasm = patient, staff, and savings benefit

20. World Asthma Guidelines
Guidelines
IV salbutamol IV aminophylline IV magnesium
Child Child Child
Australian 2014
5 mcg.kg-1.min-1 only in ICU 40 mg.kg-1
Over 60 min 10 mg.kg-1 Over 20 min
USA NIH 2007
No proof of efficacy* Not recommended 25-75 mg.kg-1
*sc adrenaline/terbutaline No time for delivery
UK BTS/SIGN 2016
15 mcg.kg-1
over 10 min
Loading dose
5mg.kg-1 over 20 min
After senior consultation
40mg.kg-1 over 20 min (max
2g)
NZ Paediatric 2007. Starship
Hospital
Acute life-threat
15mcg.kg-1
over 1 to 2 min
Consider iv in PICU
50mg.kg-1
over 20 min
Give after iv salbutamol
South African
2013
No A&E input
15 mcg.kg-1
Over 10 min
For near fatal in PICU
Severe illness
25-75 mg.kg-1
Over 20 min

21. Children 2–12 years:
Loading dose of 5 mcg/kg/minute (maximum 200 mcg/minute) for
1 hour and then infusion of 1–2 mcg/kg/minute (maximum 80 mcg).
Adults and children older than 12 years:
As continuous infusion: initial loading dose of 200 mcg over 1 minute
and then start infusion at 5 mcg/minute (can increase to 10
mcg/minute, then up to 20 mcg/minute every 15–30 minutes
according to response)
As bolus: 250 mcg over 5 minutes.
??
Aus/NZ
IV salbutamol

22. Mechanical ventilation rates
USA Krishnan 2006: 2,616 of 65,381 admissions >5yr (4%)
(ventilation increased death rate)
Doymaz 2014; early PICU terbutaline reduced mechanical ventilation;
late start: 21 of 35 (60%) early: 14 of 85 (16%)
Morris 2014: 10 weeks = 3238 : 7 ventilated (0.2%)
UK PICANet 2015: 200 of 500 admissions (40%)
AUS, Westmead, Sydney: Very rare
IV beta-2 agonist = less respiratory failure?

23. Wish List
1. Reverse Cochrane conclusions
2. Measure salbutamol /Mg serum levels (athletes)
3. Target “Hot Spots” - Knowsley, Heart of B’ham, Liverpool
600+ per 100,000 asthma admission rates
4. A Life threat asthma guide
5. NAP 7
6. Volunteer study IV MgSO4 before salbutamol

24. Wish List
Go Dutch?
Enoximone
Oral, IM, IV