The African Critical Illness Outcomes Study
Conditions: Critical Illness, Mortality
Sponsor: University of Cape Town

 
 
ACIOS Protocol v1.0 
17.04.2023                                  
                   Page 1 of 27 
 
 
Full Title  
 
 
The African Critical Illness Outcomes Study 
Short Title 
 
 
ACIOS 
Sponsor 
Department of Anaesthesia and Perioperative Medicine, University of Cape 
Town, Anzio Road, Cape Town 7925 
Funder  
National Institute for Healthcare and Care Research (NIHR) through the 
Global Health Group on Perioperative and Critical Care: “APPRISE” 
 
Chief Investigator 
 
Tim Baker 
Department of Emergency Medicine 
Muhimbili University of Health and Allied Sciences 
Dar es Salaam 
Tanzania 
Email: tim.baker@ki.se 
Telephone: +255 68 323 6765 
 
Co-Chief Investigators 
Bruce Biccard 
Department of Anaesthesia and Perioperative Medicine 
University of Cape Town  
South Africa 
Email: bruce.biccard@uct.ac.za 
Telephone: +27 (0) 76 160 6387 
 
Rupert Pearse 
Professor & Consultant in Intensive Care Medicine 
Queen Mary University of London and Barts Health NHS Trust 
Royal London Hospital 
London 
United Kingdom 
Email: r.pearse@qmul.ac.uk  
Tel: +44 (0)20 3594 0351 
 
Statistician   
 
 
Anneli Hardy 
NIHR Global Health Group on Perioperative and Critical Care: “APPRISE” 
Data management 
 
Safe Surgery South Africa   
 

 
 
ACIOS Protocol v1.0 
17.04.2023                                  
                   Page 2 of 27 
 
 
1. Signature page 
 
CI Agreement 
The study, as detailed within this Research Protocol, will be conducted in accordance with the principles of GCP, and 
the Declaration of Helsinki (64th WMA General Assembly, Fortaleza, Brazil, October 2013) and any other applicable 
regulations. I delegate responsibility for the statistical analysis and oversight to a qualified statistician (see declaration 
below). 
 
CI name: Tim Baker 
 
 
 
 
Signature:  
                                                                                       
 
Date: 17 April 2023 
 
 
 
 
 
Statistician’s Agreement 
The study as detailed within this research protocol will be conducted in accordance with the World Medical Association 
Declaration of Helsinki (64th WMA General Assembly, Fortaleza, Brazil, October 2013), Principles of ICH E6-GCP, ICH 
E9 - Statistical principles for Clinical Trials and ICH E10 - Choice of Control Groups. 
 
I take responsibility for the statistical work in this protocol is accurate and take responsibility for statistical analysis 
and oversight in this study.  
 
Statistician’s name: Anneli Hardy 
 
 
Signature:  
 
 
Date: 17 April 2023 
 
 

 
 
ACIOS Protocol v1.0 
17.04.2023                                  
                   Page 3 of 27 
 
Contents 
1. 
Signature page ................................................................................................................................ 2 
2. 
List of abbreviations ........................................................................................................................ 5 
3. 
Summary ......................................................................................................................................... 6 
4. 
Introduction .................................................................................................................................... 7 
5. 
Aim, Objectives, Research questions and Outcomes ..................................................................... 8 
5.1 
Aim .......................................................................................................................................... 8 
5.2 
Objectives ................................................................................................................................ 8 
5.3 
Research questions ................................................................................................................. 8 
5.4 
Co-primary outcomes ............................................................................................................. 9 
5.5 
Secondary outcomes ............................................................................................................... 9 
5.6 
Hospital level outcome ........................................................................................................... 9 
6. 
Methods .......................................................................................................................................... 9 
6.1 
Study design ............................................................................................................................ 9 
6.2 
Study setting ........................................................................................................................... 9 
6.3 
Hospital participation criteria ................................................................................................. 9 
6.4 
Study population (patient Inclusion criteria) .......................................................................... 9 
6.5 
Exclusion criteria ..................................................................................................................... 9 
7. 
Study Procedures .......................................................................................................................... 10 
7.1 
Hospital Recruitment ............................................................................................................ 10 
7.2 
Study data ............................................................................................................................. 10 
7.3 
Data collection ...................................................................................................................... 10 
7.3.1 Schedule of assessment ....................................................................................................... 10 
7.3.2 Hospital level data collection ............................................................................................... 10 
7.3.3 Patient level data collection ................................................................................................. 11 
7.3.4 Outcomes ............................................................................................................................. 11 
7.4 
End of Study Definition ......................................................................................................... 12 
8. 
Definitions ..................................................................................................................................... 12 
9. 
Data Handling and Management .................................................................................................. 13 
10. Statistical Analysis ......................................................................................................................... 14 
10.1 Sample size calculation ............................................................................................................. 14 
10.2 Statistical analysis ..................................................................................................................... 14 
11. Ethical Considerations ................................................................................................................... 15 

 
 
ACIOS Protocol v1.0 
17.04.2023                                  
                   Page 4 of 27 
 
12. Safety considerations .................................................................................................................... 16 
13. Monitoring and Auditing ............................................................................................................... 16 
14. Study Committees ......................................................................................................................... 16 
14.1 Study Management Team ......................................................................................................... 16 
14.2 Steering Committee .................................................................................................................. 17 
14.3 Country Coordinators ................................................................................................................ 17 
14.3 Local Coordinators .................................................................................................................... 17 
15. Dissemination and Publication Plan .............................................................................................. 17 
16. Deliverables ................................................................................................................................... 18 
17. Finance and Funding ..................................................................................................................... 18 
18. References .................................................................................................................................... 18 
Appendices ............................................................................................................................................ 21 
 
 
 
 
 

 
 
ACIOS Protocol v1.0 
17.04.2023                                  
                   Page 5 of 27 
 
2. List of abbreviations 
ACCCOS 
 
African COVID-19 Critical Care Outcomes Study 
ACIOS   
 
African Critical Illness Outcomes Study 
APORG  
 
(African Perioperative Research Group) 
APPRISE 
 
African Partnership on Perioperative and Critical Care Research 
ASOS 
 
 
African Surgical Outcomes Study 
ASOS-2  
 
African Surgical OutcomeS-2 (ASOS-2) trial 
CRISPOS  
 
Critical Illness and Sepsis Prevalence and Outcomes Study 
EECC 
 
 
Essential Emergency and Critical Care 
EuSOS  
 
European Surgical Outcomes Study 
HDU 
 
 
High Dependency Unit 
ICU 
 
 
Intensive Care Unit 
ISOS  
 
 
International Surgical Outcomes Study 
NIHR 
 
 
National Institute for Health and Care Research 
SAP 
 
 
Statistical Analysis Plan 
 
 
 
 
 

 
 
ACIOS Protocol v1.0 
17.04.2023                                  
                   Page 6 of 27 
 
3. Summary 
Short title 
ACIOS 
Methodology 
A prospective, international, multi-centre, observational study. 
Research sites 
Acute hospitals in African countries. 
Objective 
To determine the hospital point-prevalence and mortality rates of 
adult patients with critical illness in hospitals in Africa. 
Number of 
patients 
Not specified. All eligible patients in participating hospitals.    
Inclusion criteria 
All in-hospital patients aged 18 years or older in all departments and 
wards in participating hospitals in Africa. 
Exclusion criteria 
None 
Patient follow-up 
Until hospital discharge or death, censored at 7 days after inclusion. 
Primary 
outcomes 
1. The presence of critical illness  
2. 7-day in-hospital mortality 
Statistical 
analysis 
Descriptive statistics, univariate and multivariable logistic regression 
models. A statistical analysis plan will be written before analysis. 
Data collection 
duration  
One day in each hospital in September-November 2023 plus 7 days 
follow-up in each hospital 
Proposed start 
date 
1st September 2023 
Proposed end 
date 
7th December 2023 
 
 
 

 
 
ACIOS Protocol v1.0 
17.04.2023                                  
                   Page 7 of 27 
 
4. Introduction 
Critically ill patients – those in a state of ill health with vital organ dysfunction, a high risk of imminent 
death if care is not provided, and the potential for reversibility.1 – have particular needs, and managing 
these needs is a core function of hospitals. Triage at admission and on the wards is needed to identify 
these patients with critical illness.2,3 Critically ill patients need regular contact with health workers and 
close observation and frequent modifications to care, either in general wards, or in specialised locations 
such as Intensive Care Units (ICUs) and High Dependency Units (HDUs).4 Rapid Response Teams of 
acute care specialists may be implemented in hospitals to provide care when called by ward staff.5  
There are reports of gaps in the readiness and provision of critical care in hospitals in Africa.6-8 Essential 
Emergency and Critical Care (EECC) has been developed and defined as the first-line care that should 
be provided to all critically ill patients.9,10 Focusing on the first-line care in EECC is a strategy to address 
the gap in critical care. In our previous work an unmet need of EECC of 50-90% was found in hospitals 
in Malawi,8 and there have been many calls to increase the coverage of EECC to address this gap.9,11-13 
While it is accepted that critical illness and the underlying causes of critical illness are common,  the 
number of patients with critical illness has not been accurately quantified.14-16 In one region of Sweden 
we found 10% of hospital inpatients to be critically ill,17 and in a Tanzanian university hospital’s 
emergency unit, 10% of patients were critically ill at arrival.18 Global estimates have been attempted by 
using the admission rates to ICUs but this method reflects national and local uses of ICUs which vary 
greatly even between high-income countries.19 The indirect annual global estimate of 30-45 million 
adults made by extrapolating the incidence of common diseases leading to critical illness in North 
America is likely to be an underestimate as the burden of disease is greater in settings of lower 
resources.20 Moreover, the mortality of critically ill patients has not been accurately quantified, with 
reports of 18-82% in-hospital mortality rates.21-25. 
A patient’s vital signs (heart rate, respiratory rate, blood pressure, conscious level, body temperature, 
oxygen saturation) are commonly used measurements in hospital care. Deranged vital signs have been 
shown to correlate with negative outcomes such as admission to the ICU,26,27 unexpected cardiac 
arrest,27,28 and mortality,27,29 and are pragmatic and useful as criteria for the identification of critical 
illness.30,31  

 
 
ACIOS Protocol v1.0 
17.04.2023                                  
                   Page 8 of 27 
 
We will conduct a prospective, international, multi-centre, observational study of all adult in-patients 
in hospitals across Africa, based on the methods we developed in the International Surgical Outcomes 
Study (ISOS),32 European Surgical Outcomes Study (EuSOS),33 African Surgical Outcomes Study 
(ASOS),34 and African COVID-19 Critical Care Outcomes Study (ACCCOS)22 studies. Using vital-signs 
based criteria, we will determine the hospital point-prevalence of critical illness. We will collect data on 
the care provided to patients, so to determine the coverage of essential emergency and critical care. We 
will follow the adult in-hospital patients for 7 days or until hospital discharge (whichever is sooner), 
allowing an estimate of the mortality rate and patients at increased risk who are critically ill in this 
population. The knowledge generated in the ACIOS study will assist in improving organisation of acute 
hospital services with the goal of averting substantial numbers of preventable deaths in African 
hospitals.  
5. Aim, Objectives, Research questions and Outcomes 
5.1 Aim 
To investigate critical illness, its care and associated outcomes among all adult inpatients in hospitals 
across Africa. 
5.2 Objectives 
 
1. To establish the proportion of adult (18 years or older) inpatients in African hospitals that are 
critically ill. 
2. To establish the mortality rate of the critically ill patients and those who are not critically ill. 
3. To estimate the proportion of critically ill patients who receive essential emergency and critical 
care. 
4. To investigate the association between the provision of essential emergency and critical care to 
critically ill patients and mortality. 
5. To determine the availability of resources for essential emergency and critical in African 
hospitals. 
5.3 Research questions 
Among adult (18 years or older) inpatients in African hospitals:  
1. What proportion of patients are critically ill?  
2. What are the mortality rates for patients who are, and who are not critically ill?  
3. What proportion of critically ill patients receive essential emergency and critical care?  
4. What is the relationship between essential emergency and critical care provision, and mortality?  
In African hospitals: 

 
 
ACIOS Protocol v1.0 
17.04.2023                                  
                   Page 9 of 27 
 
5. What is the availability of resources for the provision of essential emergency and critical care?  
5.4 Co-primary outcomes 
• Presence of critical illness    
• In-hospital mortality (censored at 7-days)  
5.5 Secondary outcomes 
• Provision of essential emergency and critical care    
• Length of hospital stay 
5.6 Hospital level outcome 
• Availability of resources for essential emergency and critical care  
6. Methods  
6.1 Study design 
African, multi-centre prospective observational cohort study of in-hospital adult patients.  
6.2 Study setting 
Hospitals across Africa. 
6.3 Hospital participation criteria 
Any acute hospital in Africa providing adult inpatient care (see Definitions section 8). 
6.4 Study population (patient Inclusion criteria) 
All adult patients aged 18 years or over who have been admitted for inpatient care in any 
department or ward in participating hospitals.  
6.5 Exclusion criteria 
None. 

 
 
ACIOS Protocol v1.0 
17.04.2023                                                     Page 10 of 27 
 
7. Study Procedures 
7.1 Hospital Recruitment  
Hospitals will be recruited through the African Perioperative Research Group (APORG) network, the 
Essential Emergency and Critical Care (EECC) network and other networks in Africa.  
7.2 Study data 
Data will be collected on all eligible patients on the study day and then during in-hospital follow-up.  
7.3 Data collection 
A pragmatic and realistic dataset is fundamental to the success of the study. Data will be collected on 
paper on one-day in each hospital plus follow-up censored at 7 days. Data will be collected: 
• At hospital level for the availability of resources for EECC. 
• At the patient’s bedside for patient demographic and medical information, physiological signs, 
and ongoing provision of EECC and  
• From hospital records for patient outcomes. 
7.3.1 Schedule of assessment 
Event/ Visit 
Study day 
Until discharge or death, censored at 7 
days 
Hospital level data 
X 
 
Inclusion/ exclusion criteria 
X 
 
Demographic information 
X 
 
Medical information 
X 
 
Physiological signs 
X 
 
EECC provision 
X 
 
Outcomes 
 
X 
 
7.3.2 Hospital level data collection 
Data will be collected once for each hospital to assess the availability of resources for the provision of 
EECC. A checklist of resources will be used and data entered together with a key informant in the 
hospital. The key informant may be the medical-officer-in-charge or other clinician or administrator 

 
 
ACIOS Protocol v1.0 
17.04.2023                                                     Page 11 of 27 
 
who has an in-depth knowledge of the resources available in the hospital for managing critically ill 
patients, as identified by the study team’s local coordinator. In addition, data will be collected on:  
• Population served (catchment area)  
• Primary, secondary or tertiary hospital 
• Number of hospital beds 
• Number and level of critical care beds  
• Details about the reimbursement status of the hospital 
• Resources in the hospital such as staff and equipment  
7.3.3 Patient level data collection 
On the specified day of data collection, every patient fulfilling the inclusion criteria in every department 
and ward in the hospital will be included in the study. Patients who are absent from their beds when 
the study team arrive, (for example, are in an operating theatre, or undergoing a medical investigation), 
will be re-visited later the same day and included when they are back in their bed, or when they are in 
a bed where inclusion is possible such as in a surgical recovery room. Data on patient demographics, 
medical information and current care provided will be collected from the patient and from the clinical 
team. The patient’s vital sign measurements, (respiratory rate, oxygen saturation, blood pressure, heart 
rate, conscious level), will be checked by the study team using the hospital’s equipment.  If it is 
inappropriate for a patient’s vital signs to be checked – for example if the clinical team has made the 
decision to refrain from vital sign observations as the patient is in the final stage of dying, (may be 
termed ‘on an end-of-life pathway’, “moribund”, ‘gasping’  or ’late palliative phase’ by the clinical team), 
or if the patient refuses permission to measure their vital signs – then the patient will be included in the 
study but vital signs will not be measured. It will be acceptable for the study team to record the last vital 
signs recorded in the patient’s file for these patients. For women in active labour, the vital signs will be 
measured between contractions. Detailed data collection procedures will be described in the study’s 
Standard Operating Procedures. Data will be collected by clinician investigators, and/ or clinician 
researchers working at the site. 
7.3.4 Outcomes 
The patient outcomes will be reported as alive and discharged, died, or alive and still in hospital 
censored at 7-days.  

 
 
ACIOS Protocol v1.0 
17.04.2023                                                     Page 12 of 27 
 
7.4 End of Study Definition 
The end of the study is defined as the end of the 7-day follow-up for the last included patient. Data 
analysis shall follow this. 
8. Definitions 
Critical illness (co-primary outcome): a state of ill health with vital organ dysfunction, a high risk of 
imminent death if care is not provided and the potential for reversibility.1 Patients will be classified as 
critically ill if they have one or more severely deranged vital signs as in Figure 1. The cut-offs are those 
used in the Critical Illness and Sepsis Prevalence and Outcomes Study (CRISPOS) study and based on 
previous research in Tanzania and Sweden30,35,36 :  
Criterion 
Vital signs 
Definition critically ill 
Conscious level 
Conscious level (AVPU Scale) 
P or U 
Respiratory 
Respiratory rate per minute  
<8 or >30 
 
Oxygen saturation (%) 
<90 
Circulatory 
Heart rate per minute 
<40 or >130 
 
Systolic blood pressure (mmHg) 
<90 
Figure 1: Criteria for the definition of critical illness 
Hospital population: all adult patients aged 18 years or over who have been admitted for inpatient care 
in any department or ward in participating hospitals on the day of data collection. 
Essential Emergency and Critical Care (EECC): the care that all critically ill patients should receive, in all 
hospitals in the world including clinical processes such as oxygen therapy, intravenous fluids and 
patient positioning to protect the airway, as described in the 2021 global consensus.10  
Availability of resources for EECC: The 66 resources necessary for the provision of EECC  including items 
such as pulse oximeters, oxygen masks and intravenous fluids.10 
Coverage of EECC: The proportion of critically ill patients receiving EECC.  
Patients will be deemed to be receiving EECC if they are:  
• 
critically ill due to the conscious level criterion (Figure 1) and: 
o are lying in the lateral position or 

 
 
ACIOS Protocol v1.0 
17.04.2023                                                     Page 13 of 27 
 
o have an oro-pharyngeal or naso-pharyngeal airway inserted in their pharynx or 
o have an ongoing chin-life or jaw-thrust or 
o have other airway protection  
• 
critically ill due to a respiratory criterion (Figure 1) and:  
o are receiving oxygen 
• 
critically ill due to a circulatory criterion (Figure 1) and:   
o are receiving intravenous fluids or 
o are receiving a vasopressor or inotrope 
Acute Hospital: A hospital admitting acutely unwell patients – i.e. patients who have a recent onset or 
exacerbation of a somatic condition and require timely care. Acute hospitals can be owned and run by 
the government or by a private or other organisation. Hospitals that only admit chronically unwell 
patients, or only patients for rehabilitation, or only patients for elective surgery are not regarded as 
acute hospitals and are not eligible for participation in ACIOS. Hospitals, units and wards exclusively for 
patients with psychiatric conditions are not regarded as acute hospitals.  
In-hospital mortality (co-primary outcome): Death in-hospital. Patients discharged alive are not 
followed-up at home.  
1-day and 7-day outcomes: The defined time for the outcomes is from the point of inclusion of the patient 
into the study to hospital discharge or death, censored at 7-days.  
9. Data Handling and Management  
The papers containing identifiable patient data for the follow-up of clinical outcomes will be stored 
within a locked office in each hospital or institution. Data will then be pseudo-anonymised by 
generation of a unique numeric code and transcribed by local investigators onto an internet based 
electronic case-record file (e-CRF).  
Each patient will only be identified on the e-CRF by their numeric code; thus the central co-ordinating 
study team cannot trace data back to an individual patient. A participant list will be used in each 
hospital/site to match identifier codes in the database to individual patients in order to record clinical 
outcomes and supply any missing data points. This participant list will be stored on a password-
protected computer. Access to the data entry system will be based on the principle of least privilege and 

 
 
ACIOS Protocol v1.0 
17.04.2023                                                     Page 14 of 27 
 
will be protected by username and password delivered during the registration process for individual 
local investigators.   
All electronic data transfer between participating hospitals and the co-ordinating institution will be 
encrypted using a secure protocol (HTTPS/SSL 3.0 or better). Data will be anonymised during the 
transcription process using the Research Electronic Data Capture (REDCap) tools hosted by Safe 
Surgery South Africa (SSSA) who will act as the data custodian. REDCap is a secure, web-based 
application designed to support databases and data capturing for research studies. Soft limits will be 
set for data entry, prompting investigators when data were entered outside these limits. In countries 
with poor internet access, paper case record forms may be forwarded to SSSA, for entry by SSSA. 
Pseudo-anonymised (coded) data may also be sent by encrypted e-mail to the coordinating institution 
if necessary. Each institution will maintain a secure trial file including a protocol, local investigator 
delegation log, ethics approval documentation, the participant list, etc. Copies of the relevant protocols, 
approvals and investigator lists will also be kept securely in an internal drive by SSSA. A final summary 
of included patients with aggregated data of patients, and outcomes will be produced for each hospital 
together with final data submission to double check for completeness and accuracy. 
Individual patient data provided by participating hospitals remain the property of the respective 
institution, once the ACIOS report has been published. Once each local co-ordinator has confirmed the 
data provided from their hospital are both complete and accurate, they will be provided with a 
spreadsheet of the raw (un-cleaned) data for their hospital. In the ACIOS report, only summary data will 
be presented publicly, and all national, institutional and patient level data will be strictly anonymised.  
10. Statistical Analysis  
 10.1 Sample size calculation 
Our plan is to recruit as many hospitals as possible in as many African countries as possible. All eligible 
patients will be included in each hospital. We do not have a specific sample size.  
10.2 Statistical analysis 
An ACIOS statistical analysis plan (SAP) will be written prior to inspection of the final dataset. Data will 
be presented at a continental African level. All institutional and national level data will be anonymised 
prior to publication. Categorical variables will be described as proportions and will be compared using 

 
 
ACIOS Protocol v1.0 
17.04.2023                                                     Page 15 of 27 
 
chi-square tests. Continuous variables will be described as mean and standard deviation if normally 
distributed, or median and inter-quartile range if not normally distributed. Comparisons of continuous 
variables between groups will be performed using t-tests, one-way ANOVA or equivalent non-
parametric tests as appropriate. Univariate and hierarchical, multivariable, multi-level logistic 
regression models will be constructed to determine the relationship between the presence of critical 
illness and mortality and the relationship between essential emergency and critical care provision and 
mortality.  
Results of logistic regression will be reported with 95% confidence intervals. The models will be 
assessed with predefined sensitivity analyses to explore possible interacting factors and examine any 
effect on the results. A single final analysis is planned at the end of the study.  
11. Ethical Considerations  
The study will be carried out in accordance with the ethical principles in the International Conference 
on Harmonisation and Good Clinical Practice. Ethical approval will be obtained from the University of 
Cape Town with additional approvals in each country as required by national ethical committees, and 
from each institution as required by local regulatory requirements. Country Coordinators will be 
responsible for clarifying the need for ethical and regulatory approvals and for ensuring these are in 
place prior to data collection. Participating hospitals will not be permitted to record data without 
providing confirmation that the necessary ethical and regulatory approvals are in place.   
The requirement for patient consent may vary according to national regulations. We anticipate that 
patient consent will not be required by most, or even all, nations on the basis that the study is, in effect, 
a large-scale clinical audit, the dataset will only include variables documented as part of routine clinical 
care, and identifiable patient data will not leave the treating hospital. Most importantly, critically ill 
patients are frequently unable to consent for themselves due to a decreased level of consciousness and 
a requirement of consent would exclude the very patients we most wish to help. Therefore, we will use 
‘broadcasting’ signage informing patients and families that the site is participating in the study, if 
required by regulations to ensure patients are aware of the study (Appendix 1).  A precedent for this 
approach was set internationally with the EuSOS and ASOS studies. In EuSOS, consent was waived in 27 
of the 28 European countries participating,37 and in the ASOS-138 and ASOS-239 consent was waived in 
the majority of hospitals.  

 
 
ACIOS Protocol v1.0 
17.04.2023                                                     Page 16 of 27 
 
There is an ethical consideration when the study team observes a patient that is critically ill (see the 
Definitions section 8) requiring urgent care. On these occasions, the study team will immediately notify 
the clinical team about the patient’s condition and provide them with the patient’s vital signs. The 
treating clinicians will therefore be timeously alerted to the status of the patient, and will be able to 
manage the patient according to local protocols. In each hospital, the study team will offer to document 
the patients’ vital signs in the medical records – as in some low resource hospitals, patients’ vital signs 
are not checked daily due to a lack of human or material capacity, so the project may contribute to an 
improvement to the standard of care.  
As the data will only be submitted once the e-CRFs are complete, and the steering committee will only 
analyse the data after data collection is complete (and not in real time), the investigators will be unable 
to intervene in the clinical management of patients. 
12. Safety considerations 
There are no safety considerations relating to the study. There is no risk of harm to either patients or 
investigators.  
13. Monitoring and Auditing 
ACIOS study documents may be selected by the Sponsor to ensure study activities are conducted 
according to the protocol, the Sponsor’s standard operating procedures, Good Clinical Practice and the 
applicable regulatory requirements. In participating hospitals, local study documents may also be 
selected for audit on a local basis. The ACIOS study team will not routinely monitor data collection in 
individual hospitals or conduct source data verification.  
14. Study Committees 
14.1 Study Management Team 
ACIOS will be led by the Study Management Team who will be responsible for study administration, 
communication between project partners, data collection and data management.  

 
 
ACIOS Protocol v1.0 
17.04.2023                                                     Page 17 of 27 
 
14.2 Steering Committee 
A Steering Committee will be responsible for overseeing the study and its scientific conduct. 
14.3 Country Coordinators 
Country Co-ordinators will be selected to lead the project within their country and:  
• Identify hospitals and local co-ordinators in participating hospitals.  
• Assist with translation of study paperwork as required.  
• Ensure distribution of research manuals, data collection forms and other materials.  
• Ensure necessary regulatory approvals are in place prior to the start date.  
• Ensure good communication with the participating sites in the country. 
14.3 Local Coordinators 
Local co-ordinators in individual hospitals will have the following responsibilities:  
• Provide leadership for the study in their hospital. 
• Ensure all relevant regulatory approvals are in place for their institution.  
• Ensure adequate training of all relevant staff prior to data collection.  
• Supervise data collection and assist with problem solving.  
• Act as guarantor for the integrity and quality of data collected.  
• Ensure timely completion of e-CRFs. 
• Communicate with the relevant national coordinator. 
15. Dissemination and Publication Plan 
The Steering Committee will appoint a writing committee to draft the ACIOS scientific report(s) which 
will be disseminated in a timely manner. The African Partnership for Perioperative and Critical Care 
Research (APPRISE) group authorship guidelines will be followed. It is anticipated that a number of 
secondary analyses will be performed. ACIOS investigators and coordinators will be given priority to 
lead such analyses and are encouraged to do so. Participation and authorship opportunities will be 
based on contribution to the primary study. The Steering Committee will consider the quality and 
validity of any proposed study, the statistical analysis plan, a data sharing agreement, objectives that 
are in-line with the wider aims of the ACIOS project, scientific validity and the possible effect on the 
anonymity of participating hospitals prior to granting any requests for additional studies. Where 

 
 
ACIOS Protocol v1.0 
17.04.2023                                                     Page 18 of 27 
 
necessary, a prior written agreement will set out the terms of such collaborations. The Steering 
Committee must approve the final version of all manuscripts including ACIOS data prior to submission, 
whether they relate to part or all of the ACOIS dataset. In the event of disagreement within the Steering 
Committee, the Chief Investigators will make a ruling. Any analysis incorporating ACIOS data from two 
or more study sites will be considered a secondary analysis and subject to these rules. The full study 
report will be submitted to the funder and will also be made accessible via clinicaltrials.gov. 
16. Deliverables 
The main deliverables will be scientific reports of findings for general and specialty journals, abstracts 
for presentation to national and international meetings including those of the supporting societies and 
a final report summarising the overall findings. 
17. Finance and Funding 
The ACIOS study is funded by the NIHR through the Global Health Group on Perioperative and Critical 
Care grant (NIHR133850). The funders will play no role in study design, conduct, data collection, data 
analysis, reporting or interpretation of the results.  
18. References 
1. 
Kayambankadzanja RK, Schell CO, Gerdin Wärnberg M, et al. Towards definitions of critical illness and critical 
care using concept analysis. BMJ open 2022; 12(9): e060972. 
2. 
Jenson A, Hansoti B, Rothman R, de Ramirez SS, Lobner K, Wallis L. Reliability and validity of emergency 
department triage tools in low- and middle-income countries: a systematic review. European Journal of Emergency 
Medicine 2018; 25(3). 
3. 
Kruisselbrink R, Kwizera A, Crowther M, et al. Modified Early Warning Score (MEWS) Identifies Critical Illness 
among Ward Patients in a Resource Restricted Setting in Kampala, Uganda: A Prospective Observational Study. PloS 
one 2016; 11(3): e0151408. 
4. 
Phua J, Faruq MO, Kulkarni AP, et al. Critical Care Bed Capacity in Asian Countries and Regions. Critical care 
medicine 2020. 
5. 
Maharaj R, Raffaele I, Wendon J. Rapid response systems: a systematic review and meta-analysis. Critical 
care (London, England) 2015; 19(1): 254. 
6. 
Kayambankadzanja RK, Likaka A, Mndolo SK, Chatsika GS, Umar E, Baker T. Emergency and critical care 
services in Malawi: Findings from a nationwide survey of health facilities. Malawi Medical Journal 2020; 32(1): 259-
63. 
7. 
Baker T, Lugazia E, Eriksen J, Mwafongo V, Irestedt L, Konrad D. Emergency and critical care services in 
Tanzania: a survey of ten hospitals. BMC health services research 2013; 13: 140. 

 
 
ACIOS Protocol v1.0 
17.04.2023                                                     Page 19 of 27 
 
8. 
Kayambankadzanja RK, Schell CO, Mbingwani I, Mndolo SK, Castegren M, Baker T. Unmet need of essential 
treatments for critical illness in Malawi. PloS one 2021; 16(9): e0256361. 
9. 
Schell CO, Gerdin Wärnberg M, Hvarfner A, et al. The global need for essential emergency and critical care. 
Critical Care 2018; 22(1): 284. 
10. 
Schell CO, Khalid K, Wharton-Smith A, et al. Essential Emergency and Critical Care: a consensus among global 
clinical experts. BMJ Global Health 2021; 6(9): e006585. 
11. 
Crawford AM, Shiferaw AA, Ntambwe P, et al. Global critical care: a call to action. Critical Care 2023; 27(1): 
28. 
12. 
Mekontso Dessap A, Richard J-CM, Baker T, Godard A, Carteaux G. Technical Innovation in Critical Care in a 
World of Constraints: Lessons from the COVID-19 Pandemic. American journal of respiratory and critical care 
medicine 2023. 
13. 
Buowari DY, Owoo C, Gupta L, Schell CO, Baker T. Essential Emergency and Critical Care: A Priority for Health 
Systems Globally. Critical care clinics 2022; 38(4): 639-56. 
14. 
Rudd KE, Johnson SC, Agesa KM, et al. Global, regional, and national sepsis incidence and mortality, 1990–
2017: analysis for the Global Burden of Disease Study. The Lancet 2020; 395(10219): 200-11. 
15. 
Haagsma JA, Graetz N, Bolliger I, et al. The global burden of injury: incidence, mortality, disability-adjusted 
life years and time trends from the Global Burden of Disease study 2013. Injury Prevention 2016; 22(1): 3. 
16. 
Meara JG, Leather AJ, Hagander L, et al. Global Surgery 2030: evidence and solutions for achieving health, 
welfare, and economic development. Lancet 2015; 386(9993): 569-624. 
17. 
Schell CO, Baker T, al. e. The burden of critical illness among adults in a Swedish region – a population-based 
point-prevalence study; 2023. 
18. 
Mboya EA, Baker T, al. e. Critical illness at the Emergency Department of a Tanzanian National Hospital in a 
three- year period 2019-2021. 13 January 2023, PREPRINT (Version 1) available at Research Square 
https://doiorg/1021203/rs3rs-2446335/v1. 
19. 
Murthy S, Wunsch H. Clinical review: International comparisons in critical care - lessons learned. Critical care 
(London, England) 2012; 16(2): 218. 
20. 
Adhikari NK, Fowler RA, Bhagwanjee S, Rubenfeld GD. Critical care and the global burden of critical illness in 
adults. Lancet 2010; 376(9749): 1339-46. 
21. 
Kayambankadzanja RK, Schell CO, Namboya F, et al. The Prevalence and Outcomes of Sepsis in Adult Patients 
in Two Hospitals in Malawi. The American journal of tropical medicine and hygiene 2020. 
22. 
Biccard BM, Gopalan PD, Miller M, et al. Patient care and clinical outcomes for patients with COVID-19 
infection admitted to African high-care or intensive care units (ACCCOS): a multicentre, prospective, observational 
cohort study. The Lancet 2021; 397(10288): 1885-94. 
23. 
Ilori IU, Kalu QN. Intensive care admissions and outcome at the University of Calabar Teaching Hospital, 
Nigeria. Journal of critical care 2012; 27(1): 105 e1-4. 
24. 
Towey RM, Ojara S. Practice of intensive care in rural Africa: an assessment of data from Northern Uganda. 
African health sciences 2008; 8(1): 61-4. 
25. 
Gombar S, Ahuja V, Jafra A. A retrospective analysis of obstetric patient's outcome in intensive care unit of a 
tertiary care center. Journal of anaesthesiology, clinical pharmacology 2014; 30(4): 502-7. 
26. 
Subbe CP, Kruger M, Rutherford P, Gemmel L. Validation of a modified Early Warning Score in medical 
admissions. QJM : monthly journal of the Association of Physicians 2001; 94(10): 521-6. 
27. 
Kause J, Smith G, Prytherch D, Parr M, Flabouris A, Hillman K. A comparison of antecedents to cardiac 
arrests, deaths and emergency intensive care admissions in Australia and New Zealand, and the United Kingdom--the 
ACADEMIA study. Resuscitation 2004; 62(3): 275-82. 
28. 
Smith AF, Wood J. Can some in-hospital cardio-respiratory arrests be prevented? A prospective survey. 
Resuscitation 1998; 37(3): 133-7. 
29. 
Kellett J, Deane B. The Simple Clinical Score predicts mortality for 30 days after admission to an acute 
medical unit. QJM-An Int J Med 2006; 99(11): 771-81. 
30. 
Baker T, Blixt J, Lugazia E, et al. Single Deranged Physiologic Parameters Are Associated With Mortality in a 
Low-Income Country. Critical care medicine 2015; 43(10): 2171-9. 

 
 
ACIOS Protocol v1.0 
17.04.2023                                                     Page 20 of 27 
 
31. 
Baker T, Gerdin M. The clinical usefulness of prognostic prediction models in critical illness. European journal 
of internal medicine 2017. 
32. 
Global patient outcomes after elective surgery: prospective cohort study in 27 low-, middle- and high-
income countries. Br J Anaesth 2016; 117(5): 601-9. 
33. 
Pearse RM, Moreno RP, Bauer P, et al. Mortality after surgery in Europe: a 7 day cohort study. The Lancet 
2012; 380(9847): 1059-65. 
34. 
Biccard BM, Madiba TE, Kluyts H-L, et al. Perioperative patient outcomes in the African Surgical Outcomes 
Study: a 7-day prospective observational cohort study. The Lancet 2018. 
35. 
Baker T, Schell CO, Lugazia E, et al. Vital Signs Directed Therapy: Improving Care in an Intensive Care Unit in a 
Low-Income Country. PloS one 2015; 10(12): e0144801. 
36. 
Bell MB, Konrad D, Granath F, Ekbom A, Martling CR. Prevalence and sensitivity of MET-criteria in a 
Scandinavian University Hospital. Resuscitation 2006; 70(1): 66-73. 
37. 
Pearse RM, Moreno RP, Bauer P, et al. Mortality after surgery in Europe: a 7 day cohort study. Lancet 2012; 
380(9847): 1059-65. 
38. 
Biccard BM, Madiba TE, Kluyts HL, et al. Perioperative patient outcomes in the African Surgical Outcomes 
Study: a 7-day prospective observational cohort study. Lancet 2018; 391(10130): 1589-98. 
39. 
Biccard BM, du Toit L, Lesosky M, et al. Enhanced postoperative surveillance versus standard of care to 
reduce mortality among adult surgical patients in Africa (ASOS-2): a cluster-randomised controlled trial. The Lancet 
Global Health 2021; 9(10): e1391-e401. 
  
 
 

 
 
ACIOS Protocol v1.0 
17.04.2023                                                     Page 21 of 27 
 
Appendices 
Appendix 1 – Broadcasting document 
IMPORTANT PATIENT INFORMATION 
A research study is being conducted at …………………..Hospital. 
The research study is being done by Dr ………. from the Department of ……….. 
Why is this research study being done? 
To understand how sick patients are in hospital. 
 
Why are we telling you about this research study? 
All patients in this hospital are part of the research study. It is a requirement that some details 
pertaining to your clinical care are entered into a research study folder. Information from this folder 
will be used anonymously to understand how sick patients are in hospital, and what we might be 
able to do to improve the care for sick patients.  
 
Will this research study affect my care while I am in hospital? 
No. You will still receive the same care while you are in hospital. 
 
Will my name or any personal details be kept by this research study? 
No.  Your name and personal details will not be kept as part of this research study.  All information 
from the notes will be kept strictly confidential. 
Are there any risks or benefits associated with this project? 
No.  There are no risks or direct benefits associated with this research study. 
Who should I contact if I have any questions or concerns? 
Please contact Dr ………….…. on telephone…………….…. 
If you have questions about your rights or welfare as a participant, please contact the UCT Faculty 
of Health Sciences Human Research Ethics Committee on +27 (0)21 406 6338.  2 
 
 

 
 
ACIOS Protocol v1.0 
17.04.2023                                                     Page 22 of 27 
 
Appendix 2 – Case record forms (CRFs)  
2a: Hospital level CRF 
African Critical Illness Outcomes Study (ACIOS) – Hospital CRF 
Section 1: Hospital characteristics 
1. Language preference:  
 English     French     Arabic  Portuguese  Other ………………………… 
2. Hospital name:  
 
……………………………………………………… 
3. Country:  
 
……………………………………………………… 
4. Level of hospital:  
 First-level (e.g. district)     Second-level (e.g. Regional)     Third-level (e.g. University/Central/National)  
5. Type of hospital:   
 Government      
 Private  
 
 Charitable  
6. Total number of hospital beds: 
 
Total 
 
7. Number of beds in High Care Units:  
Total 
 
8. Number of beds in ICUs: 
 
 
Total 
 
9. 
Population served (catchment) of the hospital:  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
ACIOS Protocol v1.0 
17.04.2023                                                     Page 23 of 27 
 
Section 2: Available Resources 
 Are the following available in your hospital? 
 
EQUIPMENT 
Always 
Sometimes 
Never 
Don’ t know 
1 
Clock with second hand 
 
 
 
 
2 
Pulse oximeter & probe 
 
 
 
 
3 
Blood pressure measuring 
equipment (eg. 
sphygmomanometer with a 
stethoscope)  
 
 
 
 
4 
Blood pressure cuffs of 
different paediatric and 
adult sizes 
 
 
 
 
5 
Light source (lamp or 
flashlight)  
 
 
 
 
6 
Thermometer  
 
 
 
 
7 
Suction machine (electric or 
manual)  
 
 
 
 
8 
Oxygen supply 24h/day 
(cylinder, concentrator (with 
electricity supply) or piped 
oxygen)  
 
 
 
 
9 
Flow meter (if using cylinder 
or piped oxygen) 
 
 
 
 
10 
Leak-free connectors from 
oxygen source to tubing  
 
 
 
 
11 
Bag Valve Mask (resuscitator) 
– neonatal, paediatric and adult 
sizes 
 
 
 
 
12 
Sharps disposal container 
 
 
 
 
13 
External heat source 
 
 
 
 
 
 
CONSUMABLES 
Always 
Sometimes 
Never 
Don’ t know 
14 
Soap or hand disinfectant  
 
  
 
15 
Examination gloves 
 
  
 
16 
Suction catheters of paediatric and 
adult sizes 
 
  
 
17 
Guedel airways of paediatric and 
adult sizes  
 
  
 
18 
Pillows 
 
  
 
19 
Oxygen tubing 
 
  
 
20 
Oxygen nasal prongs 
 
  
 
21 
Oxygen face masks of paediatric 
and adult sizes 
 
  
 
22 
Oxygen face masks with reservoir 
bags of paediatric and adult sizes 
 
  
 
23 
Masks for Bag Valve Mask 
(resuscitator) – neonatal, paediatric and 
adult sizes  
 
  
 
24 
Compression bandages 
 
  
 
25 
Plasters or tape 
 
  
 

 
 
ACIOS Protocol v1.0 
17.04.2023                                                     Page 24 of 27 
 
26 
Gauze   
 
  
 
27 
Intravenous cannulas of 
paediatric and adult sizes  
 
  
 
28 
Intravenous giving sets  
 
  
 
29 
Skin disinfectant for cannulation   
 
  
 
30 
Syringes   
 
  
 
31 
Nutrition  
 
  
 
32 
Nasogastric tubes 
 
  
 
33 
Lubricant for nasogastric tube 
insertion 
 
  
 
34 
Intramuscular needles 
 
  
 
35 
Intraosseous cannulas of 
different sizes 
 
  
 
36 
Blankets  
 
  
 
37 
Facemasks for Infection 
Prevention and Control  
 
  
 
38 
Aprons or gowns 
 
  
 
39 
Charts/notes for 
documentation   
 
  
 
40 
Pens  
 
  
 
 
 
DRUGS 
Always 
Sometimes 
Never 
Don’ t know 
41 
Oral rehydration solution  
 
 
 
 
42 
Intravenous crystalloid 
fluids (eg. normal saline or 
Ringer’s Lactate) 
 
 
 
 
43 
Intravenous dextrose fluid 
(eg. 5%, 10% or 50%) 
 
 
 
 
44 
Oxytocin 
 
 
 
 
45 
Adrenaline  
 
 
 
 
46 
Appropriate antibiotics 
 
 
 
 
47 
Diazepam 
 
 
 
 
48 
Magnesium sulphate 
 
 
 
 
49 
Paracetamol 
 
 
 
 
50 
Local anaesthetic (eg. 2% 
lignocaine) (eg. for 
intraosseous cannulation) 
 
 
 
 
 
 
 
HR 
Always 
Sometimes 
Never 
Don’ t know 
51 
Health workers (eg nurses) 
with the ability to identify 
critical illness 24h/day  
 
 
 
 
52 
Health workers with the 
(eg nurses) ability to care 
for critically ill patients 
24hrs/day 
 
 
 
 
53 
Senior health worker (eg 
doctor) who can be called 
to assist with the care of 
critically ill patients 
24hrs/day  
 
 
 
 
 
 

 
 
ACIOS Protocol v1.0 
17.04.2023                                                     Page 25 of 27 
 
 
 
TRAINING 
Always 
Sometimes 
Never 
Don’ t know 
54 
The health workers are 
trained in the 
identification of critical 
illness 
 
 
 
 
55 
The health workers are 
trained in the care of 
critically ill patients 
 
 
 
 
 
 
 
ROUTINES 
Always 
Sometimes 
Never 
Don’ t know 
56 
The hospital has well-
defined routines for the 
identification of critical 
illness 
 
 
 
 
57 
The hospital has well-
defined routines for 
managing critically ill 
patients 
 
 
 
 
58 
There is a routine for the 
provision of EECC without 
taking into account patients’ 
ability to pay 
 
 
 
 
59 
There are routines for who 
and how to call to seek 
senior help 24hrs/day, 7 
days/week 
 
 
 
 
60 
There are routines for 
integrating EECC with 
other care including the 
definitive care of the underlying 
 
 
 
 
condition (eg. use of condition-
specific guidelines) 
 
 
 
 
 
 
 
GUIDELINES 
Always 
Sometimes 
Never 
Don’ t know 
61 
There are written 
guidelines for the 
identification of critical 
illness 
 
 
 
 
62 
There are written 
guidelines for the essential 
care of critically ill patients 
 
 
 
 
 
 
INFRASTRUCTURE 
Always 
Sometimes 
Never 
Don’ t know 
63 
Designated triage area 
(area for the identification 
of critical illness) in the 
Out-Patient Department 
or Emergency Unit (area of 
the hospital where 
patients arrive) 
 
 
 
 
64 
Running water 
 
 
 
 
65 
Designated space for the 
care of critically ill patients 
(eg. a bay, ward, high care 
unit) 
 
 
 
 
66 
Areas for separating and 
managing patients with a 
suspected or confirmed 
contagious disease from 
those without 
 
 
 
 

 
 
ACIOS Protocol v1.0 
17.04.2023                                  
           Page 26 of 27 
 
2b: Patient’s bedside CRF 
 

 
 
ACIOS Protocol v1.0 
17.04.2023                                  
           Page 27 of 27