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A comparative study of neuroprotective strategies and outcomes in neonatal hypoxic ischaemic encephalopathy
Thesis (PhD)--Stellenbosch University, 2021.
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Stellenbosch : Stellenbosch University
2021
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| _version_ | 1867614015287459840 |
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| access_status_str | Open Access |
| author | Kali, Gugulabatembunamahlubi Tenjiwe Jabulile |
| author2 | Smith, Johan |
| author_browse | Kali, Gugulabatembunamahlubi Tenjiwe Jabulile Smith, Johan |
| author_facet | Smith, Johan Kali, Gugulabatembunamahlubi Tenjiwe Jabulile |
| author_sort | Kali, Gugulabatembunamahlubi Tenjiwe Jabulile |
| collection | Thesis |
| dc_rights_str_mv | Stellenbosch University |
| description | Thesis (PhD)--Stellenbosch University, 2021. |
| format | Thesis |
| id | oai:scholar.sun.ac.za:10019.1/109865 |
| institution | Stellenbosch University (South Africa) |
| language | en_ZA |
| last_indexed | 2026-06-10T12:45:19.124Z |
| license_str | Other — see source repository |
| provenance_str_mv | Harvested via OAI-PMH from SUNScholar — Stellenbosch University Repository |
| publishDate | 2021 |
| publishDateRange | 2021 |
| publishDateSort | 2021 |
| publisher | Stellenbosch : Stellenbosch University |
| publisherStr | Stellenbosch : Stellenbosch University |
| record_format | dspace |
| source_str | SUNScholar — Stellenbosch University Repository |
| spelling | oai:scholar.sun.ac.za:10019.1/109865 A comparative study of neuroprotective strategies and outcomes in neonatal hypoxic ischaemic encephalopathy Kali, Gugulabatembunamahlubi Tenjiwe Jabulile Smith, Johan Rutherford, Mary Ann Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Paediatrics and Child Health. Neuroprotective agents Hypoxic-ischemic encephalopathy -- Neonatal Hypoxic ischaemic encephalopathy UCTD Thesis (PhD)--Stellenbosch University, 2021. 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. Agtergrond Hipoksiese isgemiese enkefalopatie(HIE) affekteer 1.15 miljoen neonate jaarliks wêreldwyd, die meerderheid van hulle is afkomstig van laer en middelinkomstelande. Dit is die hoofoorsaak van sterftes in voltermynbabas in Suid Afrika. 40% van hierdie babas oorleef met gestremdheid, wat ‘n betekenisvolle las op families en staatshulpbronne plaas.Die enigste effektiewe terapie wat mortaliteit en gestremdheid verminder is terapeutiese hipotermie. Die effek is egter beperk met baie wat steeds met gestremdheid oorleef. Terapeutiese hipotermie is nou standaardsorg in hoë-inkomstelande, maar dit word met versigtigheid aanbeveel in lande met beperkte hulpbronne. Dit is weens besorgdheid oor veiligheid en die vraag of terapie wat in spesifieke omgewings getoets is direk toepasbaar is op omgewings met ander omstandighede.Metodes‘n Retrospektiewe studie is gedoen om die veiligheidsaspekte en lewensvatbaarheid van terapeutiese hipotermie te evalueer nadat dit ingestel is as deel van roetinesorg.Die tweede studie het die uitkomste van babas wat behandel is met terapeutiese hipotermie beskryf. ‘n Derde studie is gedoen om te evalueer of die uitkomste in terapeutiese hipotermie verder verbeter kan word deur morfien by die behandeling te voeg.Die vierde studie beskryf die farmakologiese profiel van morfien in serum en serebrospinale vog in die babas wat behandel is met terapeutiese hipotermie plus morfiendosis van 25μg/kg/uur vir 72 uur. ResultateStudie 1: ons het die hantering van 100 neonate behandel met terapeutiese hipotermie oor ‘n 3 jaar periode hersien. Die meerderheid het afkoeling begin binne die terapeutiese vensterperiode van 6 uur, met ‘n mediaan toelatingstyd van 4,9 ure. Rektale temperature is gehandhaaf binne die teikenreikwydte 83% van die tyd. Komplikasies was tydelik en het nie meer gereeld gebeur as in gepubliseerde studies nie.Studie 2: ons het die uitkomste van 99 afgekoelde babas gedokumenteer. 17 babas het gesterf en 33 het nie opgevolg nie. Van die 50 oorlewendes wat teen 1 jaar geevalueer is was 82% normal en 18% het betekenisvolle inkorting gehad. ‘n Erg abnormale aEEG, erge HIE en ‘n abnormale MRI was geassosieer met swak uitkomste. ‘n Goeie suig, matige HIE, primipariteit en ‘n normale MRI was geassosieerd met ‘n goeie uitkoms. Studie 3: 45 babas is ingesluit in ‘n ewekansige studie wat terapeutiese hipotermie alleen vergelyk het met terapeutiese hipotermie plus morfien. Geen betekenisvolle verskille is gevind in die latere uitkomste tussen die groepe nie, maar babas in die terapeutiese hipotermie-plus-morfiengroep het minder lewerdisfunksie gehad asook ‘n laer konvulsielading in die vroeë kliniese verloop.Studie 4: morfienkonsentrasies is gemeet in die serum teen 24,72 en 96 uur: en teen 72 uur in die serebrospinale vog. Daar was geen toksiese vlakke met die toegediende dosisse nie. Daar was ook geen verlengde verblyf of toename in ventilasie of inotrope ondersteuning soos gevind in ander studies nie. Gevolgtrekking Terapeutiese hipotermie is uitvoerbaar en veilig in hierdie instelling. Oorlewendes het goeie uitkomstes. Die kombinasie van morfien met terapeutiese hipotermie word goed verdra en mag bydra tot breinbeskerming en moet verder ondersoek word. Doctoral 2021-02-27T07:36:03Z 2021-04-21T14:29:25Z 2021-02-27T07:36:03Z 2021-04-21T14:29:25Z 2021-03 Thesis http://hdl.handle.net/10019.1/109865 en_ZA Stellenbosch University 170 pages : illustrations application/pdf Stellenbosch : Stellenbosch University |
| spellingShingle | Neuroprotective agents Hypoxic-ischemic encephalopathy -- Neonatal Hypoxic ischaemic encephalopathy UCTD Kali, Gugulabatembunamahlubi Tenjiwe Jabulile A comparative study of neuroprotective strategies and outcomes in neonatal hypoxic ischaemic encephalopathy |
| title | A comparative study of neuroprotective strategies and outcomes in neonatal hypoxic ischaemic encephalopathy |
| title_full | A comparative study of neuroprotective strategies and outcomes in neonatal hypoxic ischaemic encephalopathy |
| title_fullStr | A comparative study of neuroprotective strategies and outcomes in neonatal hypoxic ischaemic encephalopathy |
| title_full_unstemmed | A comparative study of neuroprotective strategies and outcomes in neonatal hypoxic ischaemic encephalopathy |
| title_short | A comparative study of neuroprotective strategies and outcomes in neonatal hypoxic ischaemic encephalopathy |
| title_sort | comparative study of neuroprotective strategies and outcomes in neonatal hypoxic ischaemic encephalopathy |
| topic | Neuroprotective agents Hypoxic-ischemic encephalopathy -- Neonatal Hypoxic ischaemic encephalopathy UCTD |
| url | http://hdl.handle.net/10019.1/109865 |
| work_keys_str_mv | AT kaligugulabatembunamahlubitenjiwejabulile acomparativestudyofneuroprotectivestrategiesandoutcomesinneonatalhypoxicischaemicencephalopathy AT kaligugulabatembunamahlubitenjiwejabulile comparativestudyofneuroprotectivestrategiesandoutcomesinneonatalhypoxicischaemicencephalopathy |