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Abstract
Introduction Surgery is a cost-effective public health intervention. Access to safe surgery is a basic human right. However, there are still significant disparities in the access to and safety of surgical and anaesthesia care between low-income and middle-income countries and high-income countries. The Latin American Surgical Outcomes Study in Paediatrics (LASOS-Peds) is an international, observational, 14-day cohort study to investigate the incidence of 30-day in-hospital complications following elective or emergency paediatric surgery in Latin American countries.
Methods and analysis LASOS-Peds is a prospective, international, multicentre observational study of paediatric patients undergoing both elective and non-elective surgeries and procedures, inpatient and outpatient, including those performed outside the operating room. The primary outcome is the incidence of in-hospital postoperative complications up to 30 days after surgery. Secondary outcomes include intraoperative complications and the need for intensive care unit admission.
Ethics and dissemination This study received approval from the Institutional Review Board of the coordinating centre (Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo) as well as from all the participating centres. The study results are expected to be published in peer-reviewed journals and disseminated at international conferences.
Trial registration number NCT05934682.
- paediatric anaesthesia
- child
- epidemiology
- paediatric surgery
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STRENGTHS AND LIMITATIONS OF THIS STUDY
Latin American Surgical Outcomes Study in Paediatrics is a comprehensive, pragmatic, large-scale, prospective, multicentre study investigating postoperative complications in Latin American paediatric patients.
This study will improve our understanding of postoperative complications and mortality in Latin American children.
This pragmatic study is designed to address real-world conditions and constraints, focusing on a specific subset of postoperative complications and acknowledging that not all potential complications will be covered.
The 14-day data collection period, aligned with previous studies for practical application, may only partially capture the patient population’s variability due to potential seasonal differences.
Some centres may require informed consent due to local institutional policies, potentially reducing participant recruitment as the limited time available for obtaining consent could pose logistical challenges and affect overall participation rates.
Introduction
Surgery is a cost-effective public health measure.1 2 Nevertheless, considerable discrepancies persist in both the access to and safety of surgical and anaesthesia services between low-income and middle-income countries (LMICs) and their high-income counterparts.3 Moreover, there is a notable burden of surgical diseases among paediatric populations in LMICs, reflecting an unmet need.4 This burden is particularly pronounced in Africa and Latin America, where children constitute approximately 50% of the population under 19 years of age.5
Postoperative complications play a pivotal role in surgical morbidity and mortality.6–8 Existing data from Africa underscore variations in risk factors, incidence rates and outcomes associated with paediatric surgical complications when compared with high-income countries. Notably, the South African Paediatric Surgical Outcomes Study revealed a twofold higher incidence of complications, particularly infectious complications, and a 10-fold higher mortality rate when compared with a parallel study conducted in high-income countries.9 Similarly, a prospective study in 24 Kenyan hospitals reported a 7-day postoperative mortality of 1.7%, indicating a staggering 17-fold higher mortality rate than that in high-income countries.10 11
The African Surgical Outcomes Study investigated surgical outcomes in African adult patients and revealed a lower risk profile but a higher postoperative mortality rate than in high-income countries.12 A similar study involving adults is underway in Latin America (Latin American Surgical Outcomes Study (LASOS)).13 While a study on paediatric surgical outcomes has been conducted in Africa,14 there is an absence of data on in-hospital postoperative complications in children in Latin America.
The primary aim of the Latin American Surgical Outcomes Study in Paediatrics (LASOS-Peds) is to determine the incidence of in-hospital postoperative complications in paediatric patients in Latin America.
Methods
Design
This is a 14-day Latin American international multicentre prospective cohort study of paediatric patients (<18 years) undergoing surgery. This study is registered at www.clinicaltrials.gov (trial identification number: NCT05934682).
Patient and public involvement
The study design did not involve patients or the public.
Patient eligibility
All consecutive patients under 18 years old who are admitted to participating hospitals during the study period and undergo either elective or non-elective surgeries and procedures will be included. This includes both inpatient and outpatient surgeries and procedures, as well as those conducted outside of operating rooms that require general anaesthesia.
Inclusion and exclusion criteria
Patients will be included in the study if they meet the following criteria: (1) under 18 years of age, and (2) undergo either elective or non-elective surgeries and procedures, including those performed outside the operating room and in both inpatient and outpatient settings. Exclusions will apply to patients undergoing radiological or other procedures that do not require general anaesthesia or where general anaesthesia is performed without any procedural intervention (eg, during MRI), as well as those undergoing obstetric surgery.
Steps and data collection
At each participating hospital, local investigators will screen all paediatric patients under the age of 18 who undergo surgery during a predefined 14-day period. The start date for patient recruitment will be determined by each participating hospital within the study cohort period. Patients will be followed up until hospital discharge or for up to 30 days after surgery if they remain in the hospital.
Each hospital will individually collect and record data on an electronic or paper case recording form (CRF) for each recruited patient. The CRF paper will be stored in a secure location at each hospital, as it will initially include patient-identifiable data to allow the tracking of clinical outcomes.
All data will then be pseudonymised by the generation of a unique numeric code and transcribed by local investigators into a secure, password-protected electronic CRF on the REDCap platform.15 Although each patient will be identified on the electronic CRF by their numerical code, the study coordinating team can only trace the data back to an individual patient by contacting the local team. A patient list will be used at each hospital to match the identification code in the database to the individual patient’s recorded clinical results and to provide any missing data. Access to the data entry system will be protected by the username and password provided during the registration process to individual local investigators. All of the electronic data transfers between the participating hospitals and the coordinating centre will be encrypted by using a secure protocol (HTTPS/SSL V.3.0 or higher).
If an individual hospital is unable to access the registration form via the internet, pseudonymous coded data can also be sent by fax, registered mail, email or WhatsApp messages to the coordinating centre if necessary. Each hospital will maintain a secure trial file, including a protocol, local investigator delegation record, ethics approval documentation and a participant list.
A printout of the summary of the included patients with essential variables should be produced for each participating hospital, along with the submission of final data for double checking for completeness and accuracy.
Outcomes
The primary outcome is the incidence of postoperative complications in the hospital up to 30 days after surgery, defined as a composite endpoint of acute kidney injury16 (table 1), arrhythmia, cardiac arrest, bloodstream infection, pneumonia17 (table 2), postoperative bleeding, superficial surgical site infection, deep surgical site infection and/or body cavity or organ infection, intraoperative death and death up to 30 days after surgery. The definitions of the postoperative complications are summarised in table 3.
Definitions of acute kidney injury
Definitions of pneumonia severity
Definitions of primary composite outcomes and intraoperative adverse events
The degree of severity describes the degree of impact on the patient. Severe cases were defined according to the Clavien-Dindo classification, as shown in online supplemental table 2.18 19
Supplemental material
Secondary outcomes include identifying risk factors associated with in-hospital complications, level of local infrastructure, level of qualification of anaesthesia and surgery providers, admission to intensive care and the incidence of the following intraoperative adverse events: anaphylaxis, aspiration, bradycardia, bronchospasm, cardiac arrest, cardiovascular instability, difficult mask ventilation, difficult intubation, drug error, failed intubation, laryngospasm, low glucose and severe hypoxia (online supplemental table 2).
Study organisation
The steering committee will be chaired by the leading researcher. The study management team will be appointed by the steering committee and led by the principal investigator. This team’s duties will include the following: (1) administration of all project tasks; (2) communication between project partners (steering committee members and national and local coordinators); (3) data collection and management; and (4) preparation of reports to project sites.
The steering committee is responsible for the scientific conduct and consistency of the project. The steering committee will ensure communication between the funder, the trial management team and coordinators, as needed.
The steering committee will appoint national coordinators to lead the project in each country and (1) identify local coordinators at participating hospitals; (2) assist in translating study paperwork, as needed; (3) ensure the distribution of research manuals and other research materials; (4) ensure that necessary regulatory and ethical approvals are in place before recruitment; and (5) ensure good communication with participating sites in the country.
Local coordinators at individual institutions will have the following responsibilities: (1) provide leadership for the study at their participating institution; (2) ensure that all relevant regulatory and ethical approvals are in place for their institution; (3) ensure proper training of all relevant personnel before data collection; (4) oversee daily data collection and site recruitment, as well as follow-up on management; (5) act as a guarantor of the integrity and quality of the collected data; (6) ensure the timely completion of electronic CRFs and (7) communicate with the national coordinator.
Training will be provided via instructional videos posted on the study website. An online questionnaire must be completed for each site as part of the baseline before starting data collection.
Data management
On behalf of the steering committee, the Academic Research Organization of Instituto do Coração, Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo will be a data custodian.
The steering committee retains the authority to use the aggregated data for scientific and other purposes. Members of the LASOS-Peds study group are granted access to the pooled data for research endeavours, contingent on a thorough review and approval by the steering committee, ensuring the appropriateness of the research proposal. The primary criterion for such approvals will hinge on the quality and validity of the proposed analyses.
Public presentations of data will strictly involve summarised information, with all participating institutions anonymised, except for individualised reports provided to each institution at the study’s conclusion. It is important to note that individual patient data contributed by participating centres remain the exclusive property of the respective institutions.
Sample size calculation
All patients (<18 years) undergoing elective and non-elective surgeries and procedures, both inpatient and outpatient, including those performed outside the operating room under general anaesthesia, will be consecutively included for 14 days in a convenience sample.
Predefined statistical analysis plan
Analysis will be performed using R (R Core Team V.4.3.2, 2023).
Descriptive analysis and characterisation of the sample
This study will employ descriptive statistical measures to analyse various aspects of both continuous and categorical variables. The patients’ baseline characteristics will be presented as shown in table 4. For continuous variables, the minimum, maximum, mean, SD, median and quartiles will be calculated. Additionally, the Shapiro-Wilk test will be applied to assess the normality of each continuous variable. Categorical and ordinal variables will be expressed as absolute numbers and relative frequencies.
Baseline characteristics
Comorbidities will be assessed for frequency, and 95% CIs will be calculated. The urgency of surgery will be analysed, and a z test of the equality of proportions will be conducted to compare comorbidities within the sample.
Descriptive analysis of outcomes
Postoperative complications will be meticulously assessed, distinguishing infections as a superficial surgical site infection or a deep surgical site infection.
Specifically, for infections, distinctions will be made for abdominal cavity infection, blood infection, pneumonia and other infections. Cardiovascular complications will include arrhythmia and the occurrence of cardiac arrest.
Additional complications, including bleeding, acute kidney injury and other complications, will be evaluated. The possibility of reoperation will also be examined. The ultimate status at hospital discharge or on the 30th day after surgery will be categorised as alive or dead. The clinical outcomes will be presented as shown in table 5.
Clinical outcomes
For intraoperative adverse events, 95% CIs for proportions will be calculated, followed by tests for equal proportions to discern potential differences between adverse events and complications.
Bivariate analysis between predictors and outcomes
To assess the primary outcome, each participant will be categorised as follows: ‘No’ if the response for all complications is ‘None’, and ‘Yes’ otherwise. Additional outcomes of interest include mortality, intraoperative adverse events and admission to intensive care.
To achieve this, bivariate analyses will be conducted with all predictor variables and each outcome as follows:
For continuous variables, comparisons between patients with and without outcomes will be performed using Student’s t-test, considering the large sample size and the central limit theorem ensuring normal distribution tendencies. Analyses will be presented alongside measures of centrality and dispersion by group.
Ordinal categorical variables: a comparison between patients with and without the outcome will be conducted using the non-parametric Mann-Whitney test. Analyses will be presented alongside proportions of each category in each group (with outcome and without outcome).
Nominal categorical variables: the associations between nominal categorical variables and outcomes will be examined using either the χ2 test or Fisher’s exact test, based on χ2 test assumptions.
The aim of these comprehensive analyses is to provide a thorough understanding of the relationships between predictor variables and various outcomes of interest.
Odds ratio prediction
Preoperative risk factors contributing to postoperative complications will be predicted through logistic regression analysis. The results will be presented via univariate (unadjusted) and multivariate (adjusted) ORs, accompanied by a 95% CI.
For the univariate analysis, the OR function from the effect size package in the CRAN of R will be used. In the case of multiple models, logistic regression will be adjusted using the ‘glm’ function from the stats package. This adjustment will involve the application of all study predictors to 70% of the randomly selected data.
Variable selection will be executed using the step-backward method, systematically removing one variable at a time and assessing the impact on adjustment measures. The aim is to create a refined model that elucidates the maximum percentage of observed variability. Additionally, factors will undergo scrutiny for collinearity, and those with a variance inflation factor exceeding two will be excluded.
In the final step, the accuracy of the model will be evaluated using the remaining 30% of the data not involved in model fitting. This technique will yield a confusion matrix, providing insights into the model’s sensitivity, specificity and predictive capacity.
Ethics and dissemination
The study received approval from the Institutional Review Board at the coordinating centre (Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo) and from all participating centres. A list of centres with ethics approval is included in the supplementary material (online supplemental table 3).
National leaders will ensure that the necessary ethical and regulatory approvals are obtained for participating hospitals in their country. Hospitals can only record data if there is ethical approval or an equivalent waiver.
This study is a large-scale clinical audit; therefore, it does not pose a significant risk to the study population. In most, if not all countries, there will be no requirement for individual patient consent, as all of the data will be pseudonymised and expected to be recorded as part of routine clinical practice.
The steering committee will appoint a writing committee to write this investigation’s scientific report(s). The group will be known as the LASOS-Peds Investigators group. It is anticipated that several secondary analyses will be performed. LASOS-Peds investigators will be given priority to conduct such analyses and encouraged to do so. Participation and authorship opportunities will be based on contributions to the primary study. On request, hospitals will receive an individual report that allows for the comparison of the summary data from their particular hospital with that of their national cohort. In conjunction with the principles of data preservation and sharing, the steering committee will consider all reasonable requests to make the dataset available in whole or in part for secondary analysis and scientific publication on publication of the general dataset. The steering committee will consider scientific validity and the possible effect on the anonymity of participating hospitals before granting such requests. Where appropriate, a prior written agreement will establish the terms of such collaborations. The steering committee will consider proposals for secondary reviews based on the scientific quality of the proposal. Furthermore, the steering committee must approve the final version of all of the manuscripts before submission, whether they relate to part or all of the LASOS-Peds dataset.
Ethics statements
Patient consent for publication
Supplementary materials
Supplementary Data
This web only file has been produced by the BMJ Publishing Group from an electronic file supplied by the author(s) and has not been edited for content.
Footnotes
BMB, MJC and LAH are joint senior authors.
VCQ, GSdS and AT are joint first authors.
Contributors VQ, GSdS, AT, AV, RC, MC, NA, MN, FL, CT, FE, AG-M, RG, JH, BB, LAH, FSC, SHCR, JP and MC conceived the study and drafted the study design. AV provided administrative support. LAH, MC, NA, RC, GSdS, MC, MN, FL, CT, FE, BB, AT, AG-M, RG, JH, AA, LS, NB, NC, FC, IC, MG, AV, CP, AB, ME, AD, LS, KG, GA, LL, LP, CL and GL are the members of the steering committee and are national coordinators. VQ acted as guarantor.
Funding This work was supported by Smile Train grant number ID 0198488.
Competing interests None declared.
Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.
Provenance and peer review Not commissioned; externally peer reviewed.
Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.