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Introduction – Severe pulmonary bacterial infections are frequently complicated by systemic hypoxaemia and, in the context of acute respiratory distress syndrome (ARDS), inappropriately prolonged neutrophilic inflammation. This combination of acute hypoxaemia and persistent inflammatory response carries significant morbidity and mortality. However, patients with chronic lung disease function in the community with chronic systemic hypoxaemia and bacterial colonisation with much lower acute mortality. The HIF/PHD pathway tightly regulates neutrophilic responses to hypoxia and bacteria. Here, using acute bacterial pneumonia models, I have dissected the differences in innate immune responses to infection in acute hypoxia and following exposure to hypoxia prior to infection (‘preconditioning’). Methods – C57BL/6 mice were housed in room air or ‘preconditioned’ by exposure to 10% ambient hypoxia for seven days. They were then instilled with intratracheal Streptococcus pneumoniae (1x104 or 1x107 cfu to assess macrophage and neutrophil function respectively) under recovery anaesthesia and housed in normoxia (21% O2) or hypoxia (10% O2). At pre-determined time-points, the animals were assessed clinically for sickness and rectal temperature. Blood, bronchoalveolar lavage and tissues were taken for analysis. Transcriptome analysis by RNA-sequencing and functional glycolysis by Seahorse was performed on blood leucocytes. Results – Concurrent exposure to hypoxia and infection resulted in neutrophil-mediated morbidity and mortality. Acute hypoxia caused rapid utilisation of glucose, glycogen and fat stores resulting in systemic hypoglycaemia and death. Preconditioning with exposure to hypoxia prior to infection completely protected the host against hypoxia-induced morbidity and mortality by suppressing leucocyte glycolysis, through suppression of HIF1α, and resultant rescue from the negative energy state and cardiovascular compromise. Conclusion – Hypoxia preconditions the innate immune response by suppression of HIF1α and glycolysis in leucocytes, thereby protecting against acute hypoxia-induced mortality outcomes in acute bacterial pulmonary infection.

Abstract Background: Hypoxaemia during tracheal intubation in obstetrics remains a lifethreatening complication. This study aimed to identify common clinical preinduction predictors of difficult intubation. Methods: A retrospective analysis was performed of data pertaining to tracheal intubation in patients requiring general anaesthesia for caesarean delivery, with a gestational age from 20 weeks, and until 7 days post-delivery, obtained from an obstetric airway management registry (ObAMR) at the University of Cape Town. Data was entered anonymously into a secure UCT REDCap database. Data categories were: patient and pregnancy characteristics, airway characteristics, details of management, and operator experience. The primary aim of the study was to identify anatomical and physiological risk factors for hypoxaemia. The primary outcome was defined as arterial desaturation to < 90% during obstetric airway management. For this purpose, multivariable binary logistic regression was performed. Hypoxaemia was thus used as a composite indicator of anatomical and physiological difficulty. Results: Data was collected for 1095 general anaesthetics in the ObAMR. Overall, 143/1091 of patients (13.1%, 95%CI 11.1 to 15.4%) experienced peripheral oxygen saturation below 90%. Univariate analysis showed that 91/142 (64.1%) of patients who desaturated were obese (body mass index [BMI]> 30 kg/m2 ), compared with 347/915 (37.9%) who were obese and did not experience desaturation (p< .001). A receiver operating curve (ROC) was constructed post hoc, which showed a cut-point for BMI of 29.76, and a sensitivity of 0.66, and specificity 0.62 for the prediction of hypoxaemia. Desaturation occurred in 17.0% of patients with hypertensive disorders of pregnancy, versus 11.0 % without (p=0.005). Increasing Mallampati class was associated with an increased incidence of hypoxaemia. The incidence of hypoxaemia was 25.8% for interns, compared with 8.0 % for consultant anaesthesiologists (p=0.005). In the multivariate analysis of factors associated with hypoxaemia, body mass index (p< 0.001), room air saturation prior to preoxygenation (p=0.008), and the presence of airway oedema (p=0.027), were independently associated with hypoxaemia. Conclusions: In this study, both anatomical and physiological predictors of hypoxaemia were identified. Using this concept, a predictive tool could be developed to aid in the identification of a difficult airway in obstetrics. Simple interventions such as face mask ventilation and the use of high flow nasal oxygenation, could be introduced to protect the parturient from the consequences of life-threatening hypoxaemia.

Background In South Africa, hypertensive disorders of pregnancy are the leading cause of maternal mortality. More than 50% of anaesthesia-related deaths are attributed to complications of airway management. We compared the prevalence and risk factors for hypoxaemia (SpO2<90%) during induction of general anaesthesia in parturients with and without hypertensive disorders of pregnancy. We hypothesised that hypertensive disorders of pregnancy are associated with desaturation during tracheal intubation. Methods Data from 402 cases in a multicentre obstetric airway management registry were analysed. The prevalence of peri-induction hypoxaemia (SpO2<90%) was compared in patients with and without hypertensive disorders of pregnancy. Quantile regression of SpO2 nadir was performed to identify confounding variables associated with, and mediators of hypoxaemia.Results In the cohort of 402 cases, hypoxaemia occurred in 19% with and 9% without hypertension (estimated risk difference, 10%; 95% CI 2% to 17%; P=0.005). Quantile regression demonstrated a lower SpO2 nadir associated with hypertensive disorders of pregnancy as body mass index increased. Room-air oxygen saturation, Mallampati grade, and number of intubation attempts were associated with the relationship. Conclusions Clinically significant oxygen desaturation during airway management occurred twice as often in patients with hypertensive disorders of pregnancy, compounded by increasing body mass index. Intermediary factors in the pathway from hypertension to hypoxaemia were also identified.