Clinical experiences with the use of oxytocin injection by healthcare providers in a South-Western State Nigeria: A Cross sectional study

Background Post-Partum Hemorrhage (PPH), is a leading cause of maternal mortality in Nigeria and most low and middle income countries(LMIC). The World Health Organization(WHO) strongly recommends oxytocin as effective, affordable and the safest drug of first choice in the prevention and treatment of PPH in the third stage of labor. However, there are concerns about its quality. Very high prevalence of poor-quality oxytocin, especially in Africa and Asia has been reported in literature. Excessive and inappropriate use is also common with oxytocin in low-resource settings. Objective To assess clinical experiences with quality of oxytocin used by healthcare providers in Lagos State Nigeria. Methods It was a descriptive cross-sectional study done in 2017. Seven hundred and five respondents (doctors and nurses) who use oxytocin for obstetrics and gynaecological services were recruited from 195 health facilities (public and registered private) across Lagos State. Data collection was quantitative, using a pretested self-administered questionnaire. Data analysis was done using IBM SPSS version 21. Statistical significance was set at 5%(p<0.05). Ethical approval was obtained from Lagos University Teaching Hospital Health Research Ethics Committee. Funding support was provided by the Promoting the Quality of Medicines, a program funded by the U.S. Agency for International Development and implemented by the U.S. Pharmacopeia Convention. Results Only 52 percent of the respondents knew oxytocin should be stored at 2°C to 8°C. About 80% of the respondents used oxytocin for augmentation of labor; 68% for induction of labor, 51% for stimulation of labor and 78% for management of PPH. Forty-one percent used 20IU and as much as 10% used 30IU to 60IU for management of PPH. About 13% of the respondents have experienced use of an ineffective brand of oxytocin in their practice. Just over a third (36%) of the respondents had an available means of documenting or reporting perceived ineffectiveness of drugs in their facility. Of these, only about 12% had pharmacovigilance forms available in their facilities to report the ineffectiveness. Conclusion The inappropriate and inconsistent use of oxytocin especially overdosing likely led to the spuriously high perception of medicine effectiveness among respondents. This is also coupled with lack of suspicion of medicine ineffectiveness by clinicians as a possible root cause of poor treatment response or disease progression. Poor knowledge of oxytocin storage and consequent poor storage practices could have contributed to the ineffectiveness reported by some respondents. There is need for the establishment of a unified protocol for oxytocin use with strict compliance to the guidelines. Continued training of healthcare providers in medicines safety monitoring is advocated.

recommends Oxytocin as an effective, affordable and the safest drug of choice in the 73 prevention and treatment of PPH [2]. Oxytocin is also used intrapartum for induction, 74 stimulation and augmentation of labour when medically indicated and where benefit 75 outweighs the risk [4,5]. Oxytocin is named one of the 13 life-saving commodities by the UN 76 Commission within the continuum of care to effectively address the avoidable causes of 77 death during pregnancy and childbirth [6]and is included in the WHO Model List of Essential 78 Medicines [7]. 79 However, there are concerns about the quality of oxytocin available. Oxytocin requires stable 80 cold chain from the point of manufacture to point of use to maintain its quality [8]. It is 81 recommended to be stored in the refrigerator at 2° to 8° Celsius while some have extended 82 storage up to 20° and 25°C within a few days" [8]. A major problem of oxytocin relates to 83 heat-related degradation, inappropriate storage in the supply chain and at the health facilities. 84 In most low-income countries these storage conditions are usually very difficult to 85 maintain [9,10]. Surveillance studies have shown high prevalence of poor-quality oxytocin, 86 particularly in Africa and Asia. [10][11][12] Most common problems were insufficient or no 87 active ingredient [10,11]. Safe medicines supply is fundamental to public health [13]. Poor-88 quality medicines have the greatest potential for harming the health of consumers, with far-89 reaching consequences, which include: treatment failure, adverse drug reactions, economic 90 hardship, health problems, and death [13]. Poor quality uterotonics in circulation have dire 91 consequences. Apart from increased maternal mortality, It could also lead to performing 92 surgical procedures that could have been prevented [14]. 93 In a recent study in Nigeria, the quality audit of oxytocin injections in circulation showed an 94 alarming failure rate, up 74% of sampled oxytocin injection failed quality test [10]. Despite 95 this evidence and concerns around poor-quality medicines, epidemiologic data around quality of medicines is still spare and poor. Many healthcare providers again, do not generally 97 suspect medicines as a cause of disease progression and a contributor to treatment outcome. 98 Reports have it that obstetricians in Sub-Saharan Africa often give three vials of oxytocin to 99 ensure they get equivalent of at least one dose as prevention of PPH with one vial of oxytocin 100 is difficult. [14] This study serves as a sequel to the quality audit of oxytocin injections in 101 Nigeria and seeks to assess the clinical experience of health care providers in Lagos State were with use and their perceived effectiveness or ineffectiveness of the medicines.

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Effectiveness of oxytocin in this study is the ability of the oxytocin injection used, to achieve 106 the desired contraction within the recommended dose for a specific indication. The sample size was determined using Cochrane's formula considering the following criteria: 120 standard normal deviate at 95% confidence interval; 5% accepted error of margin and 121 proportion of reported effectiveness(52.5%) of another uterotonic from a previous study in 122 Nigeria [15].   bias. In addition, every respondent who participated in this study only had a few minutes to fill in the questionnaires. The questionnaires were not sent in advance hence no time to 198 prepare for the 'apparently correct' answer, the questionnaire clearers stated that there were 199 no right or wrong answers, they study only wanted to assess the current practice. Again

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Seven hundred and five(705) respondents were participated in the study.             Table 7 shows further analysis of different doses of oxytocin used by respondents per sector 259 of practice.

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Twelve popular brands of oxytocin were assessed in this survey. These brands were 261 previously studied audited for quality [2]. The respondents' perception of the effectiveness 262 and ineffectiveness of these brands vary significantly. These brands were de-identified for the 263 purpose of this research. were ineffective as seen in Table 9.  Table 8 shows the respondents' experience of effectiveness or ineffectiveness with use of 269 each brand of oxytocin listed however, the brands were de-identified here.     Table 11 shows that respondents in the public sector and doctors had significantly better 290 knowledge of oxytocin storage (p<0.001).

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Discussion 295 The healthcare system in most low income countries are weak. This situation is further 296 exacerbated when poor quality medicines are also in circulation. Our findings suggest poor 297 knowledge of oxytocin storage among the respondents. There was also inappropriate and 298 inconsistent use of oxytocin with the experience of ineffectiveness of oxytocin brands used 299 among respondents. Oxytocin is a peptitde with a highly unstable structure. The biggest 300 obstacle to oxytocin quality is the storage and handling before patient use. reports from a previous study done in Karnataka,India[17]. This encourages wastage and laboratory assays [11,19]  respondents. This is also coupled with lack of suspicion of medicine ineffectiveness by