Pneumonia is the leading infectious cause of under 5-year-old deaths globally and
responsible for >50% of deaths in Africa. The World Health Organization (WHO) defines
low blood oxygen saturation (SpO2) levels (hypoxemia) as 90%. Hypoxemia is identified in
31% of child pneumonia cases in Africa and is a key marker of elevated mortality risk.
When children are hypoxemic, the WHO recommends oxygen treatment. Importantly, the WHO
threshold of 90% for hypoxemia was based on concerns over limited oxygen supply and
hospital over-crowding in low- and middle-income countries (LMICs), rather than quality
evidence. In most LMICs, low oxygen flow is the mainstay of oxygen delivery. Recently, in
high-income settings high-flow nasal cannula (HFNC) oxygen has emerged as a safe and
effective alternative. HFNC oxygen delivers higher flow warmed, humidified gas via nasal
prongs to reverse hypoxemia, and potentially improve outcomes.
Recent evidence challenges whether the WHO & 90% hypoxemia threshold is optimal for
identifying all children at higher risk of mortality in LMICs. One meta-analysis from 13
LMICs reported 3.66-fold-higher odds of death (95% confidence interval (CI), 1.42, 9.47)
for children with a SpO2 93%. The investigators research from Malawi and Bangladesh
established children with pneumonia and SpO2 between 90-93% (moderate hypoxemia) is
common, and, compared to higher SpO2 levels, conveys higher mortality risk. To date,
African children with a SpO2 90-93% are not recommended for oxygen treatment.
Observational data from Malawi found children with moderate hypoxemia and treated with
oxygen had higher survival than those referred with a SpO2 90%. Currently, no randomized
trials have determined whether low flow oxygen or HFNC oxygen treatment reduces the
mortality of children with moderate hypoxemia (SpO2 90-93%) in African LMICs.
Aim 1: Conduct a pilot open label, three armed, parallel, randomized controlled trial
(RCT) comparing standard care, low-flow oxygen, and HFNC oxygen for children with
clinical pneumonia and a SpO2 90-93% to determine feasibility of a larger trial. The
investigators hypothesize it will be feasible to recruit, randomize, treat, and safely
follow-up all participants. Children with SpO2 90-93% will be randomized 1:1:1 to
standard care without oxygen (controls), low flow oxygen (intervention #1), or HFNC
oxygen (intervention #2). The primary outcome will be feasibility, defined as the
proportion of enrolled children with 2 protocol violations. Secondary outcomes include
consent refusal, intervention efficacy, participant attrition, and safety.
Aim 2: Determine the prevalence of young Malawian children with a SpO2 90-93% at the
designated study hospital. The investigators hypothesize a SpO2 90-93% will be common
among children presenting to the trial hospital. The investigators will measure the SpO2
of all children under-five years old (not limited to pneumonia cases) presenting to the
hospital 1 week per month over 12-months. Conservatively assuming an average volume of 30
children per day, based on prior data, the investigators will generate 1,400 SpO2
measurements.