Doctoral Degrees (Paediatrics and Child Health)

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Browsing Doctoral Degrees (Paediatrics and Child Health) by Author "Kali, Gugulabatembunamahlubi Tenjiwe Jabulile"

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    A comparative study of neuroprotective strategies and outcomes in neonatal hypoxic ischaemic encephalopathy
    (Stellenbosch : Stellenbosch University, 2021-03) Kali, Gugulabatembunamahlubi Tenjiwe Jabulile; Smith, Johan; Rutherford, Mary Ann; Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Paediatrics and Child Health.
    Background Hypoxic ischaemic encephalopathy affects 1.15 million neonates annually worldwide, the majority of whom are in low to middle income countries. It is the leading cause of death of term neonates in South Africa. 40% of infants survive with disability, which places a significant burden on family and state resources. The only effective therapy that reduces mortality and disability is therapeutic hypothermia, but its effect is limited with many still surviving with disability.Therapeutic hypothermia is now standard of care in high income countries, but is recommended with caution in resource-constricted countries. This is due to concerns about safety and whether a therapy tested in a different setting is directly applicable in these environments. Methods To address the safety and applicability concerns, we conducted a retrospective study to assess the feasibility and safety of therapeutic hypothermia after introducing it into routine care in our hospital.The second study documented the outcomes of infants treated after the introduction of therapeutic hypothermia.To assess whether the benefits of therapeutic hypothermia could be improved upon, the third study compared the outcomes of infants treated with therapeutic hypothermia only to those treated with therapeutic hypothermia plus morphine.The fourth study described the pharmacokinetic profile of morphine in serum and cerebrospinal fluid in the infants treated with therapeutic hypothermia plus morphine at a dose of 25 μg/kg/h for 72 hours. Results Study 1: we reviewed the management of 100 neonates treated with therapeutic hypothermia over 3 years. The majority could commence cooling within the therapeutic window of 6 hours, with a mean admission time of 4.9 hours. Rectal temperature was maintained within target range 83% of the time. Complications were transient and did not occur more frequently than in published trials. Study 2: we documented the outcomes of 99 cooled infants. 17 infants died, 33 were lost to follow up. Of the 50 survivors that could be assessed at 1 year of age, 82% were normal and 18% had significant impairment. A severely abnormal aEEG background, severe HIE and an abnormal MRI were associated poor outcome. A good suck, mild HIE, primiparity and normal MRI were associated with good outcome.Study 3: 45 neonates were included in the randomised trial comparing therapeutic hypothermia with therapeutic hypothermia plus morphine. No significant differences were found in later outcome between the groups, but infants in the therapeutic hypothermia plus morphine group had less liver dysfunction and a lower seizure burden in the early clinical course.Study 4: morphine concentrations were measured at 24, 72 and 96 hours in serum; and at 72 hours in cerebrospinal fluid. Toxic concentrations were not found at the administered dose of morphine. There was no increased length of stay, need for ventilation or inotropic support as found in other studies. Conclusion Therapeutic hypothermia is feasible and safe in this setting. Survivors have good outcomes. Combining morphine with therapeutic hypothermia at 25 μg/kg/h is tolerated well, and may confer some added neuroprotection that needs further exploration.