Adult Intensive Care in Uganda: A Systematic Review

doi:10.21203/rs.3.rs-2058941/v1

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Adult Intensive Care in Uganda: A Systematic Review

https://doi.org/10.21203/rs.3.rs-2058941/v1

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Background:

Intensive (ICU) care in many African countries, such as Uganda is comparatively underdeveloped and underprioritized, largely because of other pressing healthcare system needs. However, experiences like the COVID-19 pandemic, declines in infectious disease-associated mortality, and the ongoing epidemiologic transition make the current state of critical-care in the region important. But most countries in the region, including Uganda, do not collect ICU data, leaving published studies as one of few potential sources of robust data. Existing systematic reviews utilize this fact; however, these studies report their findings in aggregate, making country-specific conclusions impossible. As a result, aspects of critical care in several individual African countries remain unknown.

Objective:

To assess intensive care utilization in Uganda over time; specifically, we ascertain patient demographics and the most common reasons for ICU admission.

Methods:

We performed a systematic search of the following indexing databases: PuBMed, EMBASE, Google scholars, and African Journals Online prior to March 2020. To assess the gray literature, we searched the dissertation databases of the largest public universities in the country (Makerere & Mbarara University) for relevant papers. Inclusion criteria for studies were: (i) study conducted in Uganda at a facility with intensive care capacity, (ii) adult population; (iii) N>100 patients.

Findings:

A total of 10 papers, collectively reporting on 3519 adult patients and published between 2005 and 2018 met our study’s inclusion criteria. The median of the average age on admission was 35.50 [IQR: 26.11-43.4], with post-operative management as the most common reason for ICU admission. Median mortality was 37.50% [IQR: 28.5-40.5].

Conclusions:

Our study provides evidence supporting previous anecdotal reports of a comparatively low median age of patients in Uganda’s ICUs. However, we also find that most ICU research is conducted at the national referral hospital, Mulago, in the country’s capital, Kampala. This second finding highlights a significant knowledge gap, as private ICUs (whose catchment population includes Uganda’s rapidly growing middle class), and other districts in the country are not represented. As a result, these results should be interpreted cautiously. Future research studies should attempt to include private hospitals and those outside Kampala.

Systematic review registration: PROSPERO. Registration ID: CRD42020168940

Critical care

ICU

Global Health

sub-Saharan Africa

R Uganda

Critical care in Uganda, as in many sub-Saharan African countries, is both under-developed and under-prioritzed¹. The reasons are primarily economic: with the highest burden of disease in the region attributed to infectious diseases, the vast amount of already limited health-care funding is allocated to those causes of morbidity and mortality². But inadequate critical care poses many risks, both present and future: it leaves countries severely vulnerable to disease outbreaks, such as the COVID-19 pandemic and unprepared for the projected increase in demand for ICU care as complications from non-communicable diseases (NCDs) increase in prevalence³. Therefore, including critical care among health-system strengthening initiatives in sub-Saharan Africa is prudent.

To facilitate planning and efficient resource-allocation to the sector, policy makers and stakeholders need country-specific and robustly collected data. However, such data is not readily available: existent systematic reviews, for example, aggregate regional data in Africa, making country-specific conclusions impossible⁴ and most countries in the region, including Uganda, do not have ICU data registries.

By virtue of their design, standardization, and institutional review board (IRB) oversight, published studies are a source of robustly collected data in sub-Saharan Africa. Our study is premised on this consideration, as we perform a systematic search of indexed journals to elucidate patient demographics and the most common diagnoses in Uganda’s ICUs over time. To mitigate publication bias, we query available national university databases (Makerere University and Mbarara University) for unpublished, but relevant post-defense, theses.

Search strategy:

We conducted a targeted query of PuBMed, EMBASE, and African Journals Online for papers reporting on critical care in Uganda. Our search strategy was developed at the outset in consultation with team-members both in Uganda and USA. We used conceptual mapping to develop search terms after which we assessed our strategy’s sensitivity by checking if it yielded apriori-delegated cardinal papers. Our search terms are detailed in (supplement 1). The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA)⁵ guidelines (Figure 1), and checklist (Supplement 2) were adhered to throughout the study.

To mitigate publication bias (from excluding studies not published in internationally indexed journals), we searched Google scholar, African Journals Online, and ProQuest for potentially relevant publications, including conference proceedings, abstracts, and relevant graduate theses and dissertations from national universities (Makerere and Mbarara University).

Study eligibility:

Eligible studies for inclusion were those that utilized a quantitative design and had been conducted in Uganda before March 2020 (the study period was selected to mitigate publication bias following the COVID-19 pandemic) and reported on N>100 study participants.

To ensure a context-specific practical definition of ICUs, we reviewed descriptions from the World Federation of Societies of Intensive and Critical Care Medicine in addition to criteria proposed by a recently published capacity assessment (table 1)^5,6. Based on this review, we adopted the level 3 definition below of ICUs.

Table 1: ICU level definitions

Screening, extraction and quality assessment:

Two authors (EA and AA) independently screened study titles and abstracts for context and relevance. Studies passing the initial screen were then reviewed in full text by both EA and AA against the pre-established inclusion criteria. At all stages, any disagreements were resolved by mutual consensus. Data was then extracted from eligible studies and stored in an Excel database. Extraction was conducted twice to ensure accuracy.

Risk of bias assessment:

EA and AA independently assessed all eligible studies using the Joanna Briggs Institute’s (JBI) methodological guidance for systematic reviews of observational epidemiological studies to assess study quality⁷ (supplement 3).

Aggregation and analysis:

We extracted means (since medians were not consistently reported among studies) for numeric variables and proportions for categorical variables. We then computed the median and IQRs of aggregated measures in Excel ®.

Study characteristics

Ten papers reporting on N = 3519 ^8–16, with median N of 229 [IQR:124–401] per study, met the study’s inclusion criteria (Fig. 1). Most of these had been conducted between 2005 and 2018, with the earliest study (outlier) conducted in 1975.

Most studies were prospective in design and had been conducted at the national referral hospital (Mulago) located in the country’s capital city, Kampala. Only one study had been conducted outside Kampala at Lacor Hospital in Gulu (Northern region)¹⁴.

Our search of the gray literature yielded one dissertation, comparing two different continuous sedation interventions among ICU patients at Mulago Hospital in 2019.

Patient characteristics and outcomes

The median of the average age on admission was 35.50 years [IQR: 26.11–43.4], most patients were male 56.18 [IQR: 54-59.2], and the most common admission diagnoses were post-operative care management and respiratory failure (Table 2 & Fig. 2). The median of overall mortality was 37.50% [IQR: 28.5–40.5].

Assessment of publication bias:

All included studies had an N>/= 100 as initially established at the outset. Risk of bias per study assessed by the two reviewers is attached. Of note, the JBI tool does not prescribe a computed cutoff score to rule out bias (supplement 3)⁷.

To our knowledge, this is the first systematic review of ICU care in Uganda—while a previous review of critical care in low-income countries included Uganda, it reported data clustered by region, making country-specific results impossible to discern¹⁷.

Overall, our findings provide robust support for observational studies’ and anecdotal reports’ conclusions about Uganda’s ICU population—comparatively young with high mortality¹⁵. Considering the demographics and outcomes among patients in western countries provides context for this conclusion: an analysis of Medicare beneficiary data in the U.S. from 1996–2010, for example, found an average age of about 77 among patients in U.S. ICUs¹⁸. On the other hand, a population-based study assessing ICU utilization in one Canadian province in the 2000s, reported an average age of 64.5 with a 19% mortality rate^19,20.

This finding has many implications. Firstly, it suggests excess mortality among Uganda’s ICUs: young patients, on average, have few comorbidities and generally good prognosis at baseline—that mortality outcomes appear worse in Uganda’s ICU in spite this age advantage warrants further investigation. On the other hand, a comparatively low median age among ICU patients portends potential economic benefits from investing in care, as younger patients typically have many years of productivity ahead to contribute to their societies.

We additionally find that most studies were conducted at Mulago Hospital (the government-run national referral hospital). This is likely because Mulago is affiliated with the country’s government-run medical school (Makerere), whose faculty have established collaborations with foreign academic centers and donors who typically fund these studies. It is unclear why private hospitals in Kampala and elsewhere are not routinely included in these studies. Nonetheless, their omission creates a significant knowledge gap and seriously limits the external validity of their findings. Future studies should strive to include these facilities.

Ultimately, an ideal data source in the country, and the region at-large, would be a well-run registry. However, with other pressing needs competing for already limited funds, a timeline for developing such registries is impossible to predict. Initiatives, such as the Crit Care Africa project funded by the UK government to collect COVID-19 data in the region, are encouraging²¹. However, with the COVID-19 pandemic transitioning to endemic status in many developed countries, it is unclear whether donors will remain incentivized to fund such initiatives. Additionally, it is unclear whether such registries will be expanded to collect data on non-COVID related outcomes. Nonetheless, in the interim, on-going studies in the ICU setting remain an improvised source of robust prevalence and outcomes data, and as such, they should be designed to minimize statistical bias at the outset.

Limitations

Our study is limited by publication bias, as most studies were conducted at the national referral hospital (Mulago), limiting the external validity of our results. Additional publication bias arises from the fact that many studies from the region are not published in international journals. We mitigated this second risk by searching databases that primarily index African journals (African Journals Online) and by searching university databases for committee-reviewed, but unpublished, theses. These steps ensured access to robustly collected data but were unlikely to have eliminated publication bias entirely.

Study heterogeneity is an additional limitation as our aggregated data are from multiple time periods and do not account for annual fixed effects.

In conclusion, our review supports previously reported findings about Uganda’s comparatively young ICU cohort. When contrasted with data from developed countries, this finding suggests potential economic benefits from improving ICU care. The comparatively high mortality rate in spite the age advantage among Uganda’s studies raises several questions about the underlying drivers and should be investigated in future studies. We also note significant gaps in the literature, as private hospitals and districts outside the capital are not represented among current studies. Future studies should include these facilities to facilitate robust and comprehensive results.

ICU-Intensive Care Units.

IRB-Institutional Review Board.

JBI-Joanna Briggs Institute’s.

NCD-Non-Communicable Diseases.

IQR-Interquartile Range.

PRISMA-Preferred Reporting Items for Systematic Reviews and Meta-analyses.

Ethics approval and consent to participate: The study was exempted by Stanford University & University of California Los Angeles IRB boards, because it involved analysis of de-identified and already published data.

Consent for publication: Not Applicable.

Availability of data and materials: Search terms and synthesis of results included in supplementary material.

Competing interests: Not Applicable.

Funding: This study was supported by a Medical Scholars tuition grant from Stanford University School of Medicine awarded to E.A.

Authors’ contributions: EA: project conception, methods design and selection, data collection, writing. AA: project conception, data collection, writing. BS: health systems technical advisor, assistance with research strategy. SK: project conception, methods design and selection, manuscript revision, project faculty supervisor for EA and AA.

Acknowledgements: We would like to acknowledge Dr. Susan Munabi-Babigumira with the Norwegian Cochrane group whose experience with conducting systematic reviews in Uganda, given limited published studies was tremendously helpful in the design phase of the study.

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Table 2 is available in the Supplementary Files section

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Adult Intensive Care in Uganda: A Systematic Review

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Abstract

Figures

Introduction

Methods

Results

Study characteristics

Patient characteristics and outcomes

Assessment of publication bias:

Discussion

Limitations

Conclusion

Abbreviations

Declarations

References

Table

Supplementary Files

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