Cardiovascular changes in sickle cell crises and impact of arginine supplementation in vaso-occlusive crisis and acute chest syndrome

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dc.contributor.authorOnalo, Richard
dc.date.accessioned2021-11-17T23:46:29Z
dc.date.available2021-11-17T23:46:29Z
dc.date.issued2020
dc.descriptionA thesis submitted to the Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, in fulfilment of the requirements for the degree of Doctor of Philosophy, 2020en_ZA
dc.description.abstractSickle cell disease, typified by sickle cell anaemia (SCA), is prevalent in Africa and is characterised by chronic anaemia and acute exacerbation of symptoms (crisis). The crisis state is fraught with complications in various systems, predominantly the cardiopulmonary system and the skeletal system. Nitric oxide (NO) deficiency has been implicated in some of the pathological changes observed in sickle cell crisis (SCA-VOE) and arginine, the obligate substrate for NO production, is thought to have a role in the management of SCA-VOE. The study aimed to determine the influence of SCA-VOE on cardiovascular parameters and to explore the impact of arginine supplementation on the cardiac changes and the pain in children, 5-17 years, with crisis. A comparative case-controlled design was used to determine the effects of crisis on the cardiovascular system while a double-blind, placebo-controlled randomised phase 2 trial (RCT) was designed to study the impact of oral arginine(100 mg/kg/dose q8 hours for five days) on the cardiac changes and the intensity of pain. A total of 176 patients (92 in steady state and 84 in crisis) participated in the comparative case-controlled study, while 68 and 66 patients, participated in the RCT on the impact of oral arginine on cardiovascular changes and on the pain episodes in SCA-VOE, respectively. The prevalence of tachycardia, hypertension, and conduction abnormalities were higher in SCA-VOE than in the steady state. Mean myocardial ischaemia score [3.14±1.61 (crisis state) vs. 1.97±1.41 (steady state), p<0.001]; pulmonary artery systolic pressure [33.77±12.12 mmHg (crisis state) vs 22.71 mmHg (steady state), p<0.001], mean pulmonary artery pressure [25.00±7.78 mmHg (crisis state) vs. 18.67±5.16 mmHg (steady state), p<0.001] and median NT-proBNP [73.3pg/ml (crisis state) vs. 6.00 pg/ml (steady state), p = 0.001] were higher in patients with crisis. Arginine supplementation reduces mean pulmonary artery pressure, mean tricuspid regurgitation velocity, median troponin I and NT-proBNP levels, analgesic requirement, time-to-crisis resolution and length of hospital stay. In conclusion, SCA-VOE is a stressor to the cardiovascular system and the administration of oral arginine during SCA-VOE reduces the prevalence of cardiac abnormalities and ensures faster analgesia, shorter time-to-crisis resolution and a shorter hospital stayen_ZA
dc.description.librarianCKen_ZA
dc.facultyFaculty of Health Sciencesen_ZA
dc.identifier.urihttps://hdl.handle.net/10539/32017
dc.language.isoenen_ZA
dc.phd.titlePhDen_ZA
dc.titleCardiovascular changes in sickle cell crises and impact of arginine supplementation in vaso-occlusive crisis and acute chest syndromeen_ZA
dc.typeThesisen_ZA
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