Asthma Drugs ICU Magnesium Ketamine Heparin B agonists steroids Furosemide glucagon Ether Theophylline Heliox

1. Non-Conventional Drugs In
Acute Severe Asthma
Waheed Shouman
Prof of Chest Medicine
Zagazig University

2. ASA
 PEFR 33-55%
 RR more than or equal 25
 HR more than 110
 Talk in phrases

3. Life threatening asthma
 ASA plus
 Altered mental status
 Exhaustion
 Arrhythmia
 Cyanosis
 Silent chest
 PEFR < 33
 SpO2 < 92%
 PaO2 < 60%
 Pa Co2 > 45

4. Near fatal asthmas
Life threatening plus
Need for mv

5. Asthma exacerbation was not confined to
patients with severe disease or higher levels of
treatment, hence the risk of exacerbation
reflect individual susceptibility

6.  Asthma account for ¼ of ED visits per year in
USA.
 More than 330 millions have BA worldwide
 14% of children has asthma symptoms
 4.5% of young adults has asthma

7.  4000 Americans die yearly due to asthma
 Females account for 65% of asthma deaths
 350.000-400.000 die yearly due asthma
worldwide

8. Oxygen
 O2 is mandatory in ASA
 Previously it was used liberally
 Then to achieve SpO2 94-98%
 Now, to achievs SpO2 more than 92%
 May be accepted of 88%

9. B-agonists
 Salbutamol was discovered by David Jack et al
1966
 Salbutamol “albuterol” is the cornerstone of
therapy in ASA, it has immdiate actions 1-5
min “ with 4-6 hours duration

10.  Initial dose of salbutamol is 2.5- 5mg every 20
minutes for an hour“ total 7.5 – 15mg” by
nebulization, then 4-6 hours
 Doses up to 75-150 mg per hour cause no
more benefits

11.  Continuous nebulzation may be used with little
side of efffects, but more cubbersome and
annoying, hence intermittent use is preferred

12.  IV salbutamol has no more advantage
exception:
 Excessive cough
 Moribund patient
 Exhaustion

13. B-agnist
 Adrenaline dose:
 0.01 mg/kg of 1/1000 in 3 divided doses with
20 min. interval. For simplicity 0.3mg for 2
doses with maximum 3 doses

14.  Adrenaline is better they selective 2 agonists in
its alpha adrenergic effect that cause
vasoconstriction and decreased airway edema

15.  Some authors prefer iv salbutamol to
decreased time of misery and distress of
asthmatics in ASA

16.  Endohacheal adrenaline in MV asthmatics has
mixed results
 It is not advised

17.  Systemic adrenaline must be delayed in
pregnancy for its alpha adrenergic
vasoconstrictor effect on placenta

18.  Levalbuterol “xopenex” has the same efficacy
like salbutamol “at dose of 45 mcg /puff”

19. Steroids
 Systemic steroids must be used in the is the 1
first hour

20. Steroid dose
 40- 80 mg methylprednisolone 5- 10 days.
 1-2 mg kg prednisone 5 – 10 days.
 125- 250 mg / 8 hours of methylprednisolone
 100-200 mg /8 hours hydrocortisone

21.  No more than 200mg / 8 hours of
hydrocortisone or equivalent as no more
efficacy, but more myopathy esp. in MV
patients on NMBA.
 Oral steroids equal parenteral except if non
functioning gut

22.  IV steroids may have their effect within 4-6
hours
 This may occur in one hour thought
1. Reversing down regulation of B-receptions
2. Post transcription epigenetic effect

23.  Nebulized high dose ICS in ASA is
controversial, it is helpful in ED Not ICU
 Don’t stop ICS in ASA receiving systemic
steroids

24. Ipratropium
 Ipratropium needs up to 20 minutes for
its onset of action
 Ipratropium is added in 0.25-0.5 mg every 4-6
hours

25.  Ipratropium has mild additional bronchodilator
effect on B-agonists
 it is reserved for ASA

26. Aminophylline
 Aminophylline as a bronchodilator is 1/3 the
effect of B2- agonists

27.  Adding Aminophylline increase both efficacy
and side effects of B-agonist
 Side effects are being more prominent

28. Mg so4
 Mg So4 is helpful in ASA refractory to B2 –
agonists and steroids
 It is not consistently effective

29. Dose of Mg So4
 IV route preferred than inhalation
 1-2 gm / 20 min / 2 doses
 25- 75 mg/kg usual 40 mg /kg”
 1g Mg So4 = 98 mg elemental Mg

30.  20 minutes is an empirical choice, as Mg So4
can be given 1gm /min up to 4gm in
preeclampsia

31.  Rapid infusion may cause transient
hypotension flushing , or mild drowsiness and
muscle weakness with overdose

32.  Mg is an adenyl cyclase stimulator leading to
decreased Ca influx with resultant smooth
muscle relaxation

33. Ketamine
 Ketamine dose:
 0.1-2 mg / kg loading then
 0.1-2 mg / kg / hours “usually 0.5mg”
 Duration of action of bolus dose is 10-15 min
 The response is rapid in 1-5 minutes

34.  First report for ketamine in asthma:
 Betts and Parkin, 1971

35. Mode if action of ketamine:
1- Vagolytic effect
2- Increased presynaptic catecholamines
3- Antagonize bradykinins
4- Antagonize inducible NOS

36.  Ketamine is not a primary treatment for
asthma in ICU
 The worst, the MV patients, are the most
benefited
 It may be used in patients with cardiac injury

37. Ketamine may cause
 Laryngospasm
 Transient increase in ICP
 Increased muscle tone
 Apnea; if rapid infusion or high dose
 Nystagmus, rare

38. Ketamine
 ketamine increases airway secretion
 How to resolve
1. antisialogogues”: atropine, and
glycopyrrolate.
2. Benzodiazepines is the best to prevent this,
but reserved to MV patient
3. May be used in lowest dose 0.1mg /kg t
minimize this

39.  Howton et al, 1996, concluded that there was
no outcome or functional gain for ketamine
over routine treatment except for some
subjective satisfaction

40. Ketamine plus benzodiazepine may cause
hallucinations after patient awakening

41. Furosemide
 Bronchodilator effect of furosemide:
 Release of bronchodilator PG “I2”
 Blockade of bronchoconstrictor PG “F2alpha”
 Counteracting chloride transport in epithelial cells
by blockade of NA-K/CL2 cotransporter
 Blockade of inflammatory mediator releases
 Inhibit neuropeptide release they by NCNA system

42.  Most furosemide studies are small with
conflicting results
 Large scale studies are needed
 Till now, insufficient evidence, but may be
used as salvage treatment.

43.  The antiiflammatory action of furosemide is
not through its diuretic effect.
 Furosemide has no anti asthma effect when
used orally or parenterally
 Anti Asthma dose of inhaled furosemide is 20-
40 mg / dose / 4-6 hours.

44.  Results for furosemide in ASA are mixed
 One study showed that inhaled furosemide for
10-28 weeks has steroid sparing effect in
severe steroid dependent asthma

45.  No study showed any side effects of inhaled
furosemide or diuretic effect

46. Heparin
 Heparin : endogenous glucosaminoglycan
 Discovered by Mcleen 1916
 First repost as asthma therapy by Dolowitz and
dougherty 1960 With 90% symptoms relief
with IV heparin
 Bardona et al 1969, were the first to use
inhaled heparin with mixed result

47. Mechanism of action of heparin
1. Heparin binds and inhibits many
inflammatory mediators including ECP and
peroxidase
2. Heparin increase binding of SLPI with N.
elastase and Cathepsin G reducing their
activity
3. Heparin inhibit lymphocyte activation,
smooth muscle growth, vascular tone and
reduce complement activation

48.  The most effective results of heprins are in
preventing antigen induced bronchial
obstruction
 The usual dose by inhalation 5000-10000 per
dose – maximize is 100.000 U Being more
effective than cromolyn or placebo

49.  No adverse effects of use of up to 80.000 U
heparin by inhalation or any effect on bleeding
profile
 Heparin is not absorbed systemically though
bronchial mucosa

50.  Inhaled heparin has a good role in treatment of
SI-ALI

51. Heliox
 Heliox (70/30) (80/20) (60/40) may delay the
need for MV and give time for other
medicatins to have effect

52.  The most commoly used heliox 70/30 may not
help to alleviate hypoxemia
 Its best action is only in the 1st hour of use
 Heliox may be used as a vehicle for nebulized
therapy

53.  In conclusion: Heliox is used only as a trial
therapy, till now

54. Inhalational anaethetics
 Halothane, enflurane and isoflurane use is
helpful in patient failig to respond to
conventional treatment who require MV

55.  They may cause : hypotension and arrhythmia
esp in hypoxemic patient
 They may need anaesthesia machine and their
use is complex

56.  Ether enema was fist used by Maytum 1931
 Then by Kahn 1935
 50% efficacy was noticed with repeated doses
of SC ephedrine
 Morphine was used in the study

57.  IM longterme ether was used by Kahn 1937-
1939
 The study included COPD patients with
perplexing effects.
 Last vague mention for ether was in Canadian
guidelines of Asthma 1999
 Conclusion : do not use

58. Montelukast
 IV montelukast was not more effective than
placebo in children with ASA as regard FEV1,
symptoms of hospital admission.
 One small study showed rapid small  FEVI

59.  No approved muco-active drug in ASA
 No mention for lidocaine in any asthma
guidelines
 Inhaled lidocaine alone or with B2 agonist
protect against histamine induced broncho-
spasm

60. Glucagon
 Role of glucagon is extermely limited in ASA
 In 1990, one study showed that IMG IV
glucagon reversed ASA in 8/ 14 patients within
10 minutes with no complication
 It is a salvage treatment in asthma
 In 2000, Wiber et al found no role for glucagon
alone in ASA

61.  No routine use antibiotics in ASA

62. Thank You