MAGNESIUM SULFATE FOR ACUTE SEVERE ASTHMA

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MAGNESIUM SULFATEFOR ACUTE SEVERE ASTHMA

• KINETICS AND CLINICAL RESPONSE

Lucian K. DeNicola, M.D., FCCMBrian Blackwelder,
Pharm. D.University of Florida Health Science
Center/Jacksonville
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INTRODUCTION

• Magnesium sulfate has been administered to
  patients to treat acute severeasthma when
  conventional therapy with oxygen, corticosteroids
  andcontinuous aerosol beta agonists fail to
  provide adequate relief.Reported benefits have
  been limited to 11 case reports involving
  199patients. in these reports doses varied from
  17-95 mg/kg and serum levelsvaried from 2.5-5.1
  mg/dl. Clinical results were inconsistant but
  tendedto show a 9-25 improvement in airway
  resistance or clinical asthma scores.

We studied the pharmacokinetic and clinical
effects of intravenousmagnesium sulfate in
children with acute severe asthma.
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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 gt
  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 (gt2SD 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 todetermine baseline, 20
  minute and 60 minute serum magnesium
  levels,volumes of distribution and serum half
  lives. Serum magnesium levelsreported in mg/dl.
  Vd reported as ml/kg. Half life reported in
  hours.Compilations reported as mean /- standard
  deviation.

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INCREASE IN SERUM MG LEVELSWITH VARIOUS DOSES OF
MAGNESIUM SULFATE
Serum Mg levels measured at baseline, 20'
60' after a 20 min infusionfilemg-02060
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KINETICS OF MgSO4 IN CHILDRENCONCLUSIONS 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.
199322148-149filemgkinclu
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EFFECT OF MgSO4 ON MULTIPLE VARIABLESPERCENT
CHANGE AT 20 AND 60 MINUTES
MEAN DOSE 52.6/-15.5 MEAN PEAK
MG LEVEL 3.73/-0.94 file mg_reslt
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EFFECT OF MgSO4 - CAS
MG-CAS
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MgSO4 EFFECT ON MULTIPLE VARIABLESPERCENT CHANGE
AT 20 MINUTES
MGRSLT2
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MgSO4 EFFECT ON MULTIPLE VARIABLESPERCENT CHANGE
AT 60 MINUTES
MGRSLT3
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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

FILEMGCONCLU
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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.
  199322148-149.
• 2. DeNicola LK, Monem GF, Gayle MO, Kissoon N
  Treatment of Critical Status Asthmaticus in
  Children. Peds. Clin N A. 1994411293-1323.
• 3. Okayama h, Okayama M, Aikawa T, et al
  Treatment of Status Asthmaticus with
  Intravenous Magnesium Sulfate. J Asthma.
  19912811-17.
• 4. McNamara RM, Spivey WH, Skobeloff E
  Intravenous Magnesium Sulfate in the
  Management of Respiratory Failure Complicating
  Asthma. Annals Emergency Med.
  198918131-133.
• 5. Noppen M, Vanmaele L, Impens N, Schandevyl
  W Bronchodilating Effect of Intravenous
  Magnesium Sulfate in Acute Severe Bronchial
  Asthma. Chest. 199097373-376.

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