Evidence for compromised data integrity in studies of liberal peri-operative inspired oxygen.

In 2016 the World Health Organization recommended intra-operative ventilation with 80% inspired oxygen to reduce surgical site infection rates, based upon a meta-analysis of 15 randomised controlled trials, of which two were by Mario Schietroma's research group. Five trials by this group have been retracted for duplication, plagiarism, statistical error and lack of ethical approval. We analysed 40 papers by this group: 24 randomised controlled trials (5064 participants) and 16 observational studies (1847 patients). There was evidence that data integrity was compromised in 38 out of the 40 analysed papers. The distribution of baseline characteristics in randomised controlled trials was unlikely, p = 1.5 × 10-8 : continuous variables within trials were heterogeneous, p = 1.9 × 10-9 , and categorical variables were homogeneous, p = 8.5 × 10-20 . Effects of interventions varied less than expected between studies: for categorical variables, for instance postoperative wound infection, p < 1 × 10-7 , and for continuous variables, for instance HLA-DR concentration, p = 0.00001. Of 184 calculable p values, for baseline variables or results, 179 (98%) were incorrect, ranging from three orders of magnitude too small to 10 orders of magnitude too large. Twenty-one graphs occurred 81 times in 23 out of 40 papers. Liberal peri-operative oxygen did not reduce surgical site infection in a meta-analysis of 20 trials that excluded seven trials by Mario Schietroma and colleagues (odds ratio (95%CI) 0.89 (0.73-1.08); p = 0.23). An update by the World Health Organization has now excluded trials of liberal oxygen by Schietroma's group, four of which have not been retracted. We conclude that Mario Schietroma's work should not inform practice until investigated.

Validation of capnodynamic determination of cardiac output by measuring effective pulmonary blood flow: a study in anaesthetised children and piglets.

BACKGROUND: Effective pulmonary blood flow (COEPBF) has recently been validated as a technique for determining cardiac output (CO) in animals of varying sizes. The primary aim of our study was to investigate this new technique in paediatric surgical patients, compared with suprasternal two-dimensional Doppler (COSSD). METHODS: A total of 15 children undergoing cleft lip/palate surgery were investigated. Before the start of surgery, manoeuvres that were anticipated to reduce (increase in PEEP from 3 to 10 cm H2O) and increase (atropine) CO were undertaken. A study in mechanically ventilated piglets was also undertaken under general anaesthesia, measuring COEPBF and pulmonary artery (COTS) flow by ultrasonic probe as the comparator. Bias (Bland-Altman plots) and limits of agreement were assessed for effective pulmonary blood flow and COSSD or COTS. RESULTS: In paediatric patients (median age 8.5 months), overall bias was -8.1 (limits of agreement -82 to +66) ml kg-1 min-1, with a mean percentage error of 48% and a concordance rate of 64%. In the piglet model, overall bias was -1 (-36 to +38) ml kg-1 min-1, with a mean percentage error of 31% and a concordance rate of 95%. CONCLUSIONS: Under controlled experimental conditions, COEPBF is associated with excellent agreement and good trending ability when compared with the gold standard COTS. In the paediatric clinical setting, COEPBF performs well; by contrast, COSSD, an operator- and anatomy-dependent technology, appears less reliable than COEPBF.