Transcript MAGNESIUM SULFATE FOR ACUTE SEVERE ASTHMA

MAGNESIUM SULFATE
FOR ACUTE SEVERE ASTHMA
KINETICS AND CLINICAL RESPONSE
Lucian K. DeNicola, M.D., FCCM
Brian Blackwelder, Pharm. D.
University of Florida Health Science Center/Jacksonville
INTRODUCTION
Magnesium sulfate has been administered to patients to treat acute severe
asthma when conventional therapy with oxygen, corticosteroids and
continuous aerosol beta agonists fail to provide adequate relief.
Reported benefits have been limited to 11 case reports involving 199
patients. in these reports doses varied from 17-95 mg/kg and serum levels
varied from 2.5-5.1 mg/dl. Clinical results were inconsistant but tended
to show a 9-25 % improvement in airway resistance or clinical asthma scores.
We studied the pharmacokinetic and clinical effects of intravenous
magnesium sulfate in children with acute severe asthma.
METHODS - I
1. Children who met the following inclusion criteria were studied:
a) Absence of chronic cardiac or pulmonary disease
b) Within 2 standard deviations of normal height and weight
c) Acute asthma with clinical asthma score > 4
d) Failure to demonstrate a 40% improvement in CAS after
40 minutes of oxygen, steroids and continuous albuterol
aerosol (0.3-0.5 mg/kg/hr)
2. Administer 26-73.5 mg/kg intravenuous magnesium sulfate (10%)
over 20 minutes while continuing continuous albuterol aerosol.
3. Monitoring:
Continuous: HR, RR, O2 Sat
At 0 time, 20 and 60 min: BP, CAS, SAT/FIO2, serum Mg levels
When possible: PaO2, pCO2, PEFR, lung compliance
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METHODS - II
4. Serum magnesium levels were determined colorimetrically
using the Formazan Dye reaction and reported in mg/dl
5. Volume of Distribution (Vd) = Administered Dose / Concentration
6. Elimination Rate Ke =
(logn Concentration 1 - logn Concentration 2)/ change time
7. Half-life = 0.693/Ke
8. Adverse reactions were determined to be:
a) Decreased deep tendon reflexes
b) Hypotension
c) Arrythmias
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RESULTS - Pharmacokinetics
1. Study population:
a) 14 children
b) 4-180 months of age
c) 5-73 kg, one patients, 216 months, 115 kg
was
eliminated due to obesity (>2SD for wt)
2. Population averages:
a) Weight: 28.27 +/- 21
b) Age : 84.3 +/- 65.8
c) Dose: 52.6 +/- 15.4
d) MG levels: 0 Time: 1.87 +/- 0.26
20 Min: 3.73 +/- 0.99
60 Min: 2.62 +/- 0.35
e) Vd: 313.2 +/- 74.21 ml/kg
f) 1/2 life: 1.95 +/- 0.93 hours
3. No adverse effects observed
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LEGEND
Results of 14 administrations of intravenous magnesium sulfate to
determine baseline, 20 minute and 60 minute serum magnesium levels,
volumes of distribution and serum half lives. Serum magnesium levels
reported in mg/dl. Vd reported as ml/kg. Half life reported in hours.
Compilations reported as mean +/- standard deviation.
INCREASE IN SERUM MG LEVELS
WITH VARIOUS DOSES OF MAGNESIUM SULFATE
MgSO4 DOSE (mg/kg)
)ld/gm( LEVEL GM MURES
25
30
35
40
45
50
55
60
65
70
75
0
1
2
3
4
5
6
7
Serum Mg levels measured at baseline, 20' & 60' after a 20 min infusion
KINETICS OF MgSO4 IN CHILDREN
CONCLUSIONS OF SINGLE DOSE TRIAL (Dose = 52.6 +/- 15.4 mg/kg)
1. BASELINE SERUM Mg LEVELS WERE 1.87 +/- 0.26 MG/DL
Avg 20' level = 3.73 +/ -0.99
Avg 60' level = 2.62 +/- 0.35
2. VOLUME OF DISTRIBUTION = 313.2 +/- 74.2 ML/KG
3. 1/2 LIFE = 1.95 +/- 0.93 HOURS
4. RECOMMENDED DOSE TO ACHIEVE SERUM LEVEL = 4.2
MG/DL:*
with high baseline and small Vd: 49.9 mg/kg
with low baseline and large Vd: 101.3 mg/kg
with avg baseline and avg Vd: 73.6 mg/kg
5. FOR OUR PURPOSES WE ARE GOING TO CONTINUE OUR
STUDIES WITH 70 MG/KG
*Fesmire FM: intravenous Magnesium for Acute Asthma. Annals of Emergency Medicine. 1993;22:148-149
file:mgkinclu
EFFECT OF MgSO4 ON MULTIPLE VARIABLES
PERCENT CHANGE AT 20 AND 60 MINUTES
PARAMETER
BASELINE
N-20"
% CHANGE 20"
N-60"
% CHANGE-60"
RESPIRATIONS
35+/-18
14
-4.8/-17
10
-1.1+/-23
pO2
82+/-5
1
12.7+/-0
2
17.8+/-6
CAS
5.8+/-1
11
-10.7+/-14
7
-27.3+/-17
SAT/FIO2
242+/-111
7
-3.4+/-4.8
8
7.8+/-33
COMPLIANCE
11.8+/-8
3
0.25+/-0.35
3
13.7+/-10
HR
153+/-23
14
-.74+/-7.3
10
-7+/-6
pCO2
48+/-11
4
-10+/-14.5
2
2.3+/-4
PEFR
159+/-44
4
36+/-33
2
20+/-11
MEAN DOSE = 52.6+/-15.5 MEAN PEAK MG LEVEL = 3.73+/-0.94
EFFECT OF MgSO4 - CAS
PATIENTS
652
02 TA SAC NI EGNAHC %
SETUNIM
-50
-40
-30
-20
-10
0
10
20
MG-CAS
797
455
141
671
1
3
MgSO4 EFFECT ON MULTIPLE VARIABLES
PERCENT CHANGE AT 20 MINUTES
RESP
-40
EGNAHC TNECREP
-20
0
20
40
60
80
MGRSLT2
CAS
COMP
PCO2
MgSO4 EFFECT ON MULTIPLE VARIABLES
PERCENT CHANGE AT 60 MINUTES
RESP
-50
-40
EGNAHC TNECREP
-30
-20
-10
0
10
20
30
40
50
MGRSLT3
CAS
COMP
PCO2
CONCLUSIONS
1. FOR CHILDREN 4-180 MONTHS OF AGE THE VOLUME OF
DISTRIBUTION FOR MgSO4 IS 313.2 +/- 74.2 ml/kg.
2. HALF-LIFE OF A SINGLE DOSE OF MgSO4 IN THESE CHILDREN
IS 1.95 +/- .93 HOURS.
3. THE CLINICAL PARAMETERS MEASURED DID NOT CHANGE
SIGNIFICANTLY WITH A MEAN DOSE OF 52.6 MG/KG,
ACHIEVING A PEAK SERUM MG LEVEL OF 3.73 MG/DL
4. HOWEVER, THERE WAS A DISTINCT TENDENCY FOR CLINICAL
PARAMETERS TO IMPROVE SUGGESTING THAT OPTIMIZING
THE DOSE AND SERUM LEVELS MAY PRODUCE MEASURABLE
IMPROVEMENT
5. INTRAVENOUS MgSO4 ADMINISTRATION APPEARS TO BE
SAFE IN DOSES UP TO 70 MG/KG
FILE:MGCONCLU
IMPLICATIONS
1. FUTURE STUDIES SHOULD OPTIMIZE THE DOSE OF MgSO4 TO
ATTEMPT TO ACHIEVE SERUM LEVELS OF 4.2 MG/DL
2. SINCE INTRAVENOUS MgSO4 IN DOSES UP TO 70 MG/KG
SEEMS TO BE SAFE, MORE LIBERAL INCLUSION CRITERIA MAY
BE USED IN FUTURE STUDIES
3. SINCE IT IS DIFFICULT TO ADMINISTER EFFORT DEPENDANT
TESTS, IE, PEFR TO YOUNG CHILDREN FUTURE STUDIES
MIGHT BEST BE PERFORMED ON OLDER, MORE COOPERATIVE
CHILDREN IN OUTPATIENT SETTINGS.
4. DEFINITIVE RESULTS REQUIRE RANDOMIZED, DOUBLE BLIND,
PLACEBO CONTROLLED STUDIES
5. THIS STUDY NEITHER ENCOURAGES NOR DISCOURAGES THE
USE OF CONTINUOUS MgSO4 INFUSIONS IN FUTURE STUDIES.
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REFERENCES
1. Fesmire FM: Intravenous Magnesium for acute asthma. Annals of
Emergency Medicine. 1993;22:148-149.
2. DeNicola LK, Monem GF, Gayle MO, Kissoon N: Treatment of Critical
Status Asthmaticus in Children. Peds. Clin N A. 1994;41:1293-1323.
3. Okayama h, Okayama M, Aikawa T, et al: Treatment of Status
Asthmaticus with Intravenous Magnesium Sulfate. J Asthma.
1991;28:11-17.
4. McNamara RM, Spivey WH, Skobeloff E: Intravenous Magnesium Sulfate
in the Management of Respiratory Failure Complicating Asthma.
Annals Emergency Med. 1989;18:131-133.
5. Noppen M, Vanmaele L, Impens N, Schandevyl W: Bronchodilating
Effect of Intravenous Magnesium Sulfate in Acute Severe
Bronchial Asthma. Chest. 1990;97:373-376.
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