Brief Reports

Indian Pediatrics 2001; 38: 646-649  

Role of Intra-muscular Magnesium Therapy in Mangement of Persistent Apnea and Prevention of Adverse Life Threatening Events

From the Department of Pediatrics, Regional Institute of Maternal and Child Health, Dr. S.N. Medical College, Jodhpur, India.
Correspondence to: Dr. Mukesh Gupta, E-22/10 Umaid Hospital Campus, Jodhpur, Rajasthan, India.

Manuscript received: June 25, 1997; Initial review completed: August 26, 1997; Revision accepted: December 29, 2000.

Neonatal apnea is a symptom of postnatal stress, sign of physiological immaturity and remains an exceedingly common clinical problem of neonatal respiration. Apnea in neonatal period is a significant clinical problem, specially among preterm neonates, with associated morbidity and mortality. Apneic spells, solitary or recurrent, occur in over 80% of infants less than 30 weeks and in only 7% at 34-35 weeks. Of these, 40% of the episodes are central or diaphragmatic, 10% are obstructive and 50% mixed(1).

Idiopathic post neonatal apnea is defined as a sudden, unexpected attack of apnea that first occurs after the infant has been discharged from the neonatal unit. In the sickest infants the apneic attack is a form of shock with apnea, bradycardia and acute respiratory distress, and/or neuro-muscular hyper irritability(2).

Many drugs are being used in the treatment of apnea. Unfortunately, only few available medications have proved to be really helpful. Now-a-days, magnesium is also claimed to be effective in management of apenea. It is also claimed to reduce the recurrence of postnatal apnea(3). This study was planned to evaluate the role of magnesium sulphate in manage-ment of persistent apnea of preterm babies and in prevention of post neonatal apnea.

Over a one year study period all neonates with apnea were identified. The apneic attacks were managed as per a standard protocol. All babies received supplemental humidified oxygen. Each apneic episode was aborted by giving tactile stimulation and/or bag and mask ventilation. Pharmacotherapy with doxapram and/or aminophylline was started in an apneic event. Patients with three or more than three episodes in 24 hours were considered as non-responders. Such non-responders were alternately allocated to two groups. Group 1 received magnesium sulfate intramuscularly for 5 days in a dose of 0.1 ml/kg/day in a single dose and Group II was managed by the conventional therapy as outlined above. Those with more than 3 episode of apnea in 24 hours in either group were put on mechanical ventilation. All babies having gross CNS malformations or severe birth asphyxia were excluded from the study. The infants entered into the trial were followed for a period of six months for morbidity in form of post-neonatal apnea, seizures and near miss sudden infant death syndrome (apparent life threatening events or ALTE)(4).

Each single attack of apnea was labelled as an apneic episode and a series of apneic episodes as an apneic event. Bradycardia was defined as heart rate below 100 per minute. In the magnesium supplemented group, pre and post treatment magnesium levels were estimated with a conventional colorimeter.

All continuous variables were analyzed by comparing the group mean by Student’s ‘t’ test and proportions were analyzed by Chi-square test.

A total of 210 consecutive newborns with apnea were observed during the study period. Of these 164 babies could be successfully managed by supportive therapy and standard apnea management by physical stimulation and/or pharmacotherapy with doxapram and/or amniophylline. There were 46 babies who did not respond to conventional therapy (34 with idiopathic apnea of prematurity and 12 had secondary apnea). Of these, 23 were allocated to receive magnesium supple-mentation and 23 were managed conser-vatively. The magnesium supplemented group had significantly fewer apneic events and duration of mechanical ventilation (Table I). Only 37 out of 46 neonates could be followed till the end of 24 weeks of life, there being a drop out of 4 in Group 1 and 5 in Group II. No ALTE episodes were noted in Group I infants but in Group II two neonates developed post-neonatal apnea and 3 neonates had convulsions at 12 weeks of age (27.7%) (p = 0.05). There was no mortality in either group upto 6 months of age.

Maternal level of serum magnesium did not show any correlation with neonatal levels and other clinicotherapeutic variables of apnea. In the follow-up, ALTE were observed in 5 neonates from non-supplemented group (2-post neonatal apnea, 3-generalized seizures). These infants had normal hematological and biochemical parameters, negative septic screening and normal EEG. But hypocalcemia and hypomagnesemia were documented in all of them. They were supplemented with calcium and magnesium for 5 more days and showed no further recurrence of ALTE. No side effects of magnesium supplementation were evident.

Magnesium supplementation in neonates with idiopathic apnea of prematurity resulted in a significant benefit on number of events of apnea and the need for IPPV support. Magnesium can affect the pathogenesis of idio-pathic apea in two ways - firstly by decreasing the recurrence and secondly reducing the severity of apnea. The duration of IPPV requirement was statistically more when magnesium supplementation was not given. But the duration of pharamacotherapy required and total periods of apnea were not affected by supplementation. The magnesium supple-mentation reduces the risk of recurrence of neonatal apnea is in agreement with an earlier report(5) where oral magnesium reduced chances of readmission for apnea.

Atwell(6) identified the age at risk for magnesium deficiency as between 1 and 3 months of age prior to onset of mixed feeding. This is also the age considered critical for occurrence of ALTE and SIDS(7,8). The clinical characteristics of our infants and the age of post-neonatal morbidity are similar to Atwell’s observations(6).

Caddell studied 20 infants with post neonatal apnea retrospectively. Seven babies treated for 5 or more days with magnesium supplementation showed no recurrence of apnea requiring resuscitation or rehospital-ization. Of the 13 untreated babies (not given magnesium in their first admission for apnea) 6 were readmitted for apnea, 2 of them twice, 3 of the 13 were subsequently magnesium treated with no further recurrence of apena.

In a similar parallel retrospective study(3) of 200 premature infants with idiopathic apnea and bradycardia approximately 50% had hypomagnesemia, 61 of these infants were treated with magnesium and 134 untreated. Fifty six of the treated babies were followed -up for at least six months and did not require readmission and all survived. Of the 118 untreated who were followed-up 28 were rehospitalized for apnea and 5 died of SIDS (9).

Prevention of post neonatal apnea and seizures in supplemented group though not statistically significant, merits attention as the findings are on the same lines as observations made by other workers(2,6).

In conclusion, magnesium sulfate supplementation deserves a trial as an adjuvant to the prevailing therapy of neonatal apnea.

Contributors : MG coordinated the study particularly its design. SM carried out data collection, patient enrolment and clinical monitoring. PS drafted the paper helped by RBS and RJ. KM helped in data collection and clinical work. MG will act as the guarantor for the paper.

Funding: None.
Competing interests: None stated.

Table I Comparison of Magnesium Supplemented and Control Groups (Mean±SD)

Key Messages

Magnesium supplementation had a role in prevention of post-neonatal life threatening events. Magnesium supplementation significantly reduced the total apneic attacks and duration of artificial ventilatory support. This supplemental therapy had no significant side effects.

1. David J, Henderson S. Apnea in prematurity: In: Respiratory Control Disorders in Infants and Children. Ed. Bakerman RC, Maryland, Williams and Wilkins. 1994; pp 161-197.

2. Caddell JL. Magnesium therapy in infants with post-neonatal apnea. Magnesium 1988; 7: 103-106.

3. Caddell JL. Magnesium therapy in premature infants with apnea neonatorum. J Am Coll Nutr 1988; 7: 5-76.

4. Consensus statement. National Institute of Health Consensus Development Conference on Infantile Apnea and Home Monitoring. Pediatrics 1987; 79: 292-299.

5. Byne PA. Magnesium therapy in premature neonates with apnea neonatorum. J Am Coll Nutr 1988; 7: 520.

6. Atwell JD. Magnesium deficiency following neonatal surgical procedures. J Pediatr Surg 1996; 1: 427-440.

7. Valdes-Dapena MA. Sudden unexplained infant death. 1970 through 1975: An evaluation in understanding. Pathol Ann 1977; 12: 117-145.

8. Kraus JF, Borhani N. Post neonatal sudden unexplained death in California: A cohort study. Am J Epidemiol 1972: 95: 497-570.

9. Caddell JL. Reply: Magensium therapy in premature infants with apnea neonatorum. J Am Coll Nut 1988; 7: 185-191.