ICU Journal Club – Low vs High Oxygenation Targets Dr Swapnil Pawar
Ascending Cholangitis Dr Swapnil Pawar
Renal Calculus Dr Swapnil Pawar
Dr Swapnil Pawar
Written by – Dr Jose Chacko
The Children’s Oxygen Administration Strategies Trial (COAST) trial is a multicentre, open, fractional-factorial RCT conducted in 4 Ugandan and 2 Kenyan hospitals.
Children aged 28 days to 12 years, hospitalised with a history of respiratory illness and any one of 2013 WHO clinical definitions of severe pneumonia plus hypoxaemia (SpO2 <92%) were enrolled into either
Stratum A (SpO2<80%): 1:1 randomised to high flow nasal therapy (HFNT) via OptiFlow or low flow oxygen delivery
Stratum B (SpO2 80-91%): 1:1:2 randomised to HFNT via OptiFlow, LFO delivery, or control (permissive hypoxaemia; control arm received LFO if SpO2 fell below 80%.). Children in stratum B required two SpO2 readings of 80-91% 5 minutes apart.
Children were managed in general paediatric wards where mechanical ventilation facilities were largely unavailable.
HFNT using the AIRVO device
For the first 15 mins of HFNT were in room air (21%) and oxygen titrated in if saturations remained < 92%.
Nasal cannulae/prongs; escalated to higher flow rates through masks
Flow rates were titrated up over the first 30 min to 1 hour against SpO2 ≥92% up to 4/min by nasal cannula. If SpO2 ≥92% not maintained, switched to masks, flows up to 15 l/min. Target SpO2: 92%
SpO2 checked at 15, 30, and 60 minutes
The control arm received LFO if SpO2 fell below 80%.
Oxygen therapy was weaned/stopped if SpO2 remained ≥92% on room air
Restarted if SpO2 dropped to <92%
At 48 hours children on HFNT were weaned to LFO
Maintenance fluids of between 2.5-4 mls/kg/hour
Antibiotics, antimalarials, antipyretics, anticonvulsants, treatment for hypoglycaemia
Transfusion with 20 mls/kg haemoglobin <5g/dl
Post-discharge children were clinically assessed (including neurological and developmental assessment) at 28-days post-randomization. Kilifi developmental milestone assessment motor, language, and personal-social development. Only children with cognitive dysfunction were followed up beyond 28 days, at 90 days.
The sample size was determined using simulations, assuming a 1:2 ratio between strata A:B and 48-hour mortality in the LFO arms of 26% and 9% in strata A and B respectively. Overall, 4,200 children provided at least 90% power to detect a 33% relative risk reduction (RR) for liberal (HTNT or LFO) vs permissive hypoxaemia (control), and a 25% RR for HFNT vs. LFO.
The trial was stopped prematurely in February 2020 by the Trial Steering Committee on the grounds of feasibility as a result of a civic campaign to terminate the trial in Uganda, which deemed permissive hypoxaemia (control) unethical
1842 eligible children were enrolled. 388 in stratum A; 194 children were randomised to HFNT and 194 to LFO. Of 1454 children in stratum B, 363 to were randomised to HFNT, 364 to LFO and 727 to control.
Mortality at 48 h
The aOR for liberal versus control was 1.16 (95% CI 0.49, 2.74) p=0.728 and for HTNT versus LFO was 0.60 (0.33, 1.06) p=0.076
A substantial size of reduction in 48-hour mortality with HFNT compared to LFO particularly in severely hypoxaemic children (40%)
Mortality at 28 days
Treatment failure at 48 hours (persistent hypoxaemia: SpO2<92% with respiratory distress)
Treatment failure in survivors to 48 hours post-randomisation (SpO2<92% plus respiratory distress) was somewhat lower in HFNT versus LFO aOR 0.75 (0.40, 1.41) and lower for liberal versus control strategy aOR: 0.37 (0.19, 0.71)
Time to hypoxaemia resolution (SpO2 ≥92%)
Duration of respiratory (oxygen/HFNT) support
In stratum A, median duration (interquartile range, IQR) on respiratory support by HFNT was longer than for LFO 36.6 hours (9.0, 48.0) versus 32.1 hours (7.4, 47.7). In stratum B duration of support by HFNT and LFO were similar (8.4 (2.8, 26.8) and 6.8 (2.5, 25.3)
In stratum A, although the number of hours of supplemental air/oxygen blend was similar over the 48- hours period, the mean (standard deviation) volume of oxygen (litres) used was lower in HFNT: 2731L/child (2733) than LFO: 3591L/child (4128).
In stratum B, both the duration of administration of supplemental air/oxygen [9.8 (14.6) versus 15.9 (16.6)] hours and the oxygen volume received [969L/child (1890) versus 1481L/child (2480)] were considerably lower in HFNT than LFO.
Neurocognitive and/or developmental sequelae assessed at Day-28
Length of initial hospital stay
Re-admission to hospital by 28 days
Day-28 anthropometric status.
The COAST trial found no evidence that oxygen-conservative strategy (only providing oxygen if saturations fell to <80%) in children with a range of SpO2 80% to 91% was harmful (mortality through Day-28 or neurocognitive impairment) compared to the usual method of oxygen delivery (LFO).
A substantial size reduction in 48-hour mortality with HFNT compared to LFO particularly in severely hypoxaemic children (40%)
Stratum B, which included 78% of all eligible children, in those allocated to HFNT hypoxaemia was corrected in most cases by HFNT using room air with no supplemental oxygen, without any evidence of harm.
In neonates, medical oxygen used during resuscitation increases mortality, myocardial injury and renal injury.
Type II error possible
Mortality lower compared with previous trials;
Rarely maintain sa02 that low
We can not recommend using oxygen targets of 80-92% to initiate oxygen therapy based on this trial.
High flow oxygen delivery device is beneficial in hypoxic children.
Another carefully designed large RCT is needed.
Dr Swapnil Pawar September 19, 2021
Dr Swapnil Pawar August 29, 2021