----------
> From: Shane Curran <[log in to unmask]>
> To: [log in to unmask]

> nick macartney wrote
> >The doses were boluses of 0.5 mg Salbutamol IV. My personal record was
50 mg
> >over about 10 mins. No, I have not made a mistake with the dose, or the
the
> >timing. I hyave not had to ventilate a young asthmatic for ages.
> >Gets off soap box, and takes cover.......
> >Nick
> >Dr NJD Macartney MBBS FRCA
>
> I am interested in these industrial doses>
> As someone who is about to come into asthma season in the region(300 in
one
> day last year) and who has actually ventilated a few asthmatics(without a
> death) i would be interested in anything that staves it off especially
with
> JHO's about to face it alone off 5 minutes until they can get help
> putting the tube in these people is easy
> its keeping them alive while you are doing it that is the problem
> Did anyone ever write these up?
> Shane

There was an excellent paper from melbourne published in the Lancet that
lookes at the benefit of IV salbutamol vs nebulised salbutamol in children
with acute severe asthma. The use of IV bronchodilators was discussed on
the list a while ago. I have repasted the previous posts at the end of this
message (with abstracts).

Simon Carley
Anaesthetics / Intensive Care
Stepping Hill Hospital
Stockport
England
[log in to unmask]

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> From: Dr. Bryan Walpole <[log in to unmask]>
>
> Why are you still using aminophylline for asthma?  We understand it
confers no
> benefit over beta 2 agonists +- ipratropium & prednisolone, cant quote
the
> ref's but can get them if you wish!
>

You must be talking about the excellent RCT of early intravenous salbutamol
in the early management of asthma published in the Lancet.
Browne GJ, Penna AS, Phung X, Soo M. Randomised trial of intrevenous
salbutamol in eatly management of acute severe asthma in children. Lancet
1997;349:301-305

There follows 7 abstracts detailing RCT's on aminophylline versus Beta2
agonists in the treatment of severe asthma.
Search strategy - OVID interface 1993-1997
[asthma exp. ti sh.ab] AND [aminophylline ti.ab.sh (exp)] AND [High quality
RCT filter from Trisha Greenoughs paper in the BMJ]

references 1, 3-7 show no
benefit and reference 2 shows an adverse outcome with aminophylline. Fairly
convinving stuff. Can't find a metaanalysis yet but will feed back if I do.
If not there appears to be ebough RCT's to give it a go!

REFERENCES
1.
Needleman JP. Kaifer MC. Nold JT. Shuster PE. Redding MM. Gladstein J .
Department of Pediatrics, University of Maryland School of Medicine,
Baltimore.
Theophylline does not shorten hospital stay for children admitted for
asthma.
Archives of Pediatrics & Adolescent Medicine. 149(2):206-9, 1995 Feb.

Abstract
OBJECTIVE: To determine if the use of intravenous theophylline, in the form
of aminophylline, when added to systemic corticosteroids and aerosolized
beta 2-agonists, enhances the improvement of children with acute asthma
exacerbations. DESIGN: A double-blind, placebo-controlled, randomized,
clinical trial.
SETTING: The University of Maryland Medical Center, Baltimore, an urban
primary- and tertiary-care pediatric medical center.
PATIENTS: Forty-two children, aged 2 to 18 years, admitted to the hospital
for acute exacerbations of asthma.
METHODS: Patients were randomized to receive either intravenous
theophylline to maintain a serum level greater than 55 mumol/L or a placebo
infusion. All patients received methylprednisolone and nebulized albuterol.
A clinical severity score was assessed twice daily.
RESULTS: The mean length of stay for the treatment and control groups was
52.3 +/- 32.3 hours and 48.2 +/- 26.6 hours, respectively (t = 0.45, P =
..65). The rate of improvement of clinical scores was similar.
CONCLUSION: These data suggest that the addition of theophylline to
albuterol and corticosteroids does not enhance improvement of children
admitted to the hospital with asthma.

2.
Rodrigo C. Rodrigo G .
Centro de Terapia Intensiva, Asociacion Espanola la en Socorros Mutuos,
Montevideo.
Treatment of acute asthma. Lack of therapeutic benefit and increase of the
toxicity from aminophylline given in addition to high doses of salbutamol
delivered by metered-dose inhaler with a spacer [see comments].
Comment in: Chest 1995 Aug;108(2):590-1
Chest. 106(4):1071-6, 1994 Oct.

Abstract
We conducted a randomized, double-blind, placebo-controlled study to
determine if intravenous aminophylline adds any benefit to high doses of
inhaled salbutamol in patients who presented for treatment of acute asthma.
We studied 94 patients (mean age, 35.6 +/- 11.2 years) with moderate to
severe acute asthma. All patients received therapy with salbutamol
delivered with metered-dose inhaler (MDI) into a spacer device (Volumatic)
in four puffs (400 micrograms) at 10-min interval, and intravenous
hydrocortisone (500 mg). Patients were randomly assigned to receive either
a loading dose of intravenous aminophylline followed by a routine infusion
(n = 45) or an equal volume of placebo as a loading dose and infusion (n =
49). The two groups showed no differences in measurements of peak
expiratory flow, FEV1, and FVC at baseline and at the end of treatment.
However, the patients treated with aminophylline had significantly more
adverse effects (p < 0.05). There were no differences in the final mean
dose of salbutamol (6.3 +/- 44.5 mg for the placebo group and 5.8 +/- 4.2
mg for the aminophylline group), hospital admission rate (10.2 percent for
the placebo group and 9.0 percent for the aminophylline group), and mean
duration of Emergency Department treatment (2.5 +/- 1.83 h for the placebo
group and 2.37 +/- 1.75 h for the aminophylline group). The results were
similar when the patients were divided in accord with the degree of
respiratory obstruction (baseline FEV1 < 30 percent of predicted) and
theophylline level at 30 min of treatment (placebo group patients with
theophylline level < 10 mg/L vs aminophylline group patients with
theophylline level > or = 10 mg/L). We conclude that intravenous
aminophylline adds to the toxicity but not the efficacy of inhaled
salbutamol in the treatment of acute exacerbations of asthma.
-----------------------------------------------------------------------
3.
Zainudin BM. Ismail O. Yusoff K .
Department of Medicine, University Kebangsaan Malaysia, Kuala Lumpur.
Effect of adding aminophylline infusion to nebulised salbutamol in severe
acute asthma.
Thorax. 49(3):267-9, 1994 Mar.

Abstract
BACKGROUND--The benefit of adding theophylline to beta 2 agonists in acute
asthmatic attacks has been debated frequently. METHODS--In an open
randomised study 25 patients with severe acute asthma who presented to the
emergency department were treated with either a combined nebulised
salbutamol (5 mg/dose) and aminophylline infusion (0.6-0.9 mg/kg/hour), or
nebulised salbutamol alone. RESULTS--The responses to treatment as measured
by peak expiratory flow (PEF) and the time taken to achieve maximum PEF
were similar in both groups. Side effects were observed more commonly in
patients receiving the combined treatment. CONCLUSIONS--Nebulised
salbutamol is equally efficacious in acute asthma when given alone or in
combination with aminophylline.
------------------------------------------------------------------------
4.
Coleridge J. Cameron P. Epstein J. Teichtahl H .
Western Hospital, Melbourne, Vic.
Intravenous aminophylline confers no benefit in acute asthma treated with
intravenous steroids and inhaled bronchodilators.
Australian & New Zealand Journal of Medicine. 23(4):348-54, 1993 Aug.

Abstract
BACKGROUND: The role of intravenous aminophylline in acute asthma is
unclear despite meta-analysis of many studies comparing aminophylline with
other bronchodilator therapies. AIMS: The aim of this study is to determine
whether continuous aminophylline infusion confers any benefit in acute
severe asthmatics treated with intravenous steroids and inhaled
bronchodilators.
METHODS: The study was randomised, double-blind and placebo-controlled. All
patients received nebulised salbutamol (1 mL of 0.5%) and ipratropium
bromide (1 mL of 0.025%) with glycol diluent (1 mL) at 0, two, four, six,
eight and 12 hours, and six-hourly thereafter. In addition all patients
were given intravenous hydrocortisone 250 mg six-hourly and oxygen to
maintain normoxia. Aminophylline infusions were adjusted to maintain
therapeutic levels. Peak expiratory flow rate (PEFR) was measured before
and after nebulised bronchodilator on a two-hourly basis in the Emergency
Department (ED) and six-hourly on the inpatient wards.
RESULTS: Thirty-one patients were clinically sufficiently improved within
12 hours to be discharged home from the ED. The remaining 28 patients were
admitted to the inpatient ward for a total trial duration of 48 hours. No
significant difference was found between the placebo and treatment groups
for measurements of PEFR, or for the duration of stay of the patients in
hospital. The power of the study was 80% for a 25% to 33% difference at a
5% level of significance. Presentation values of PEFR and arterial blood
gases did not predict which patients would require inpatient admission and
which could be safely discharged home from the ED.


------------------------------------------------------------------------
5.
Huang D. O'Brien RG. Harman E. Aull L. Reents S. Visser J. Shieh G.
Hendeles L .
University of Florida, Gainesville.
Does aminophylline benefit adults admitted to the hospital for an acute
exacerbation of asthma? [see comments].
Comment in: Ann Intern Med 1993 Dec 15;119(12):1216
Annals of Internal Medicine. 119(12):1155-60, 1993 Dec 15.
Abstract
OBJECTIVE: To determine the effect of adding intravenous theophylline
(administered as aminophylline) to nebulizations of albuterol and
intravenous methylprednisolone in adults hospitalized for acute asthma.
DESIGN: Randomized, placebo-controlled, double-blind study.
SETTING: Inpatient service of a tertiary-care, university teaching
hospital.
PATIENTS: 21 adults (22 to 48 years old)--10 in the aminophylline group and
11 in the placebo group.
INTERVENTIONS: Nebulized albuterol, 2.5 or 5.0 mg every 0.5 to 4 hours;
intravenous methylprednisolone, 60 mg every 6 hours; and either
individualized doses of aminophylline or placebo for 48 hours.
MEASUREMENTS: Forced expiratory volume in 1 second (FEV1), the number of
"as needed" albuterol nebulizations and total dose, asthma symptom scores,
and adverse effects.
RESULTS: At admission from the emergency department, the mean +/- SD
baseline FEV1 was 49% +/- 19% of the predicted value in the aminophylline
group and 43% +/- 13% of the predicted value in the placebo group. The
improvement in FEV1 at 3 hours was greater in the aminophylline group (29%
+/- 23% compared with 10% +/- 10% in the placebo group; mean difference, 19
percentage points; 95% CI, 3 to 35 percentage points; P = 0.023). At 48
hours, FEV1 was 75% +/- 19% of the predicted value in the aminophylline
group and 58% +/- 15% of the predicted value in the placebo group (mean
difference, 17 percentage points; CI, 0.2 to 34.8 percentage points; P =
0.048). Aminophylline-treated patients required fewer nebulizations of
albuterol (10.3 +/- 3.8 compared with 16.4 +/- 5.3; mean difference, -6.1;
CI, -10.3 to -1.8) and less total dosage (34 +/- 16 mg compared with 70 +/-
34 mg; mean difference, -36 mg; CI, -60.6 to -11.3 mg P = 0.02). No
statistical differences were observed in asthma symptom scores or frequency
of adverse effects.
CONCLUSIONS: Individualized doses of intravenous theophylline added to
frequent nebulizations of albuterol and intravenous methylprednisolone
appear to benefit adults admitted to the hospital with acute asthma and are
well tolerated when serum concentrations are maintained in the therapeutic
range.


------------------------------------------------------------------------
6.
Authors
Murphy DG. McDermott MF. Rydman RJ. Sloan EP. Zalenski RJ .
Department of Emergency Medicine, Cook County Hospital, Chicago.
Aminophylline in the treatment of acute asthma when beta 2-adrenergics and
steroids are provided.
Archives of Internal Medicine. 153(15):1784-8, 1993 Aug 9.

Abstract
BACKGROUND: The purpose of this study was to test the contribution of
aminophylline in improving peak expiratory flow rate (PEFR) during
emergency department treatment of acute asthma when metaproterenol sulfate
and steroid therapy are also provided.
METHODS: In a prospective, randomized, double-blind, and placebo-controlled
trial at a municipal hospital emergency department, 44 patients with acute
asthma, aged 18 to 45 years, with theophylline levels below 28 mumol/L, who
had failed to achieve a PEFR of 40% predicted after one nebulized
metaproterenol treatment, were recruited. An aminophylline or placebo
loading dose and maintenance infusion were administered. All patients
received hourly nebulized metaproterenol and initial methylprednisolone
sodium succinate. The PEFR was measured hourly for 5 hours. Two-factor
repeated-measures analysis of variance of improvement in PEFR
([final-initial PEFR]/predicted PEFR) was assessed.
RESULTS: There was no difference in improvement of PEFR at any hour between
the treatment and placebo groups. After 5 hours, the difference in
improvement ratio was 0.40 (aminophylline) vs 0.36 (placebo) (P = .30; n =
22 in each group). The treatment group suffered more tremor, nausea or
vomiting, and palpitations (P < .05).
CONCLUSION: In the emergency department setting, aminophylline contributes
no significant improvement in PEFR when beta 2-agonists and corticosteroids
are being provided, while causing more side effects.
------------------------------------------------------------------------
7.
Carter E. Cruz M. Chesrown S. Shieh G. Reilly K. Hendeles L .
Department of Pediatrics, University of Florida College of Medicine,
Gainesville.
Efficacy of intravenously administered theophylline in children
hospitalized with severe asthma [see comments].
Comment in: J Pediatr 1993 Mar;122(3):403-5
Journal of Pediatrics. 122(3):470-6, 1993 Mar.
Abstract

PURPOSE: To determine whether intravenously administered theophylline, when
added to frequently nebulized albuterol and intravenously administered
methylprednisolone, benefits children hospitalized with severe asthma.
DESIGN: Prospective, randomized, placebo-controlled, parallel-group,
double-blind study.
SETTING: Inpatient pediatric service at a tertiary-care teaching hospital.
PATIENTS: Twenty-one children 5 to 18 years of age.
INTERVENTIONS: All patients received 2.5 to 5.0 mg of nebulized albuterol
every 20 minutes to every 6 hours, intravenously administered
methylprednisolone (1 mg/kg every 6 hours), and either intravenously
administered theophylline (as aminophylline) or placebo for 36 hours. Serum
theophylline concentrations were maintained between 55 and 110 mumol/L
(between 10 and 20 micrograms/ml) by adjusting loading doses and continuous
infusion rates.
MEASUREMENTS AND MAIN RESULTS: Forced expired volume in 1 second (FEV1) and
clinical score were measured at 0, 1, 3, 6, 12, 24, and 36 hours after the
start of each individual study. The total number of nebulizations, total
albuterol dosage, adverse effects, and duration of hospital stay were
recorded. Twelve children received theophylline and nine received placebo.
The two groups did not differ significantly in age, sex, or baseline FEV1.
In both groups, clinical score significantly improved from baseline by 12
hours, and FEV1 by 24 hours (p < 0.05). There were no significant
differences between the groups in FEV1 or clinical score at any of the
measured time points. There were no significant differences in rate of
improvement in FEV1, total number of nebulizations, total albuterol dosage,
or duration of hospital stay. Adverse effects were mild and infrequent and
did not differ significantly between the two groups.
CONCLUSIONS: Theophylline, at therapeutic concentrations, did not
additionally benefit children hospitalized with severe asthma who were
being treated frequently with nebulized albuterol and with
methylprednisolone intravenously.



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