Urinary angiotensinogen excretion in Australian Indigenous and non-Indigenous pregnant women.

The intrarenal renin-angiotensin system (iRAS) is implicated in the pathogenesis of hypertension, chronic kidney disease and diabetic nephropathy. Urinary angiotensinogen (uAGT) levels reflect the activity of the iRAS and are altered in women with preeclampsia. Since Indigenous Australians suffer high rates and early onset of renal disease, we hypothesised that Indigenous Australian pregnant women, like non-Indigenous women with pregnancy complications, would have altered uAGT levels. The excretion of RAS proteins was measured in non-Indigenous and Indigenous Australian women with uncomplicated or complicated pregnancies (preeclampsia, diabetes/gestational diabetes, proteinuria/albuminuria, hypertension, small/large for gestational age, preterm birth), and in non-pregnant non-Indigenous women. Non-Indigenous pregnant women with uncomplicated pregnancies, had higher uAGT/creatinine levels than non-Indigenous non-pregnant women (P < 0.01), and levels increased as pregnancy progressed (P < 0.001). In non-Indigenous pregnant women with pregnancy complications, uAGT/creatinine was suppressed in the third trimester (P < 0.01). In Indigenous pregnant women with uncomplicated pregnancies, there was no change in uAGT/creatinine with gestational age and uAGT/creatinine was lower in the 2nd and 3rd trimesters than in non-Indigenous pregnant women with uncomplicated pregnancies (P < 0.03, P < 0.007, respectively). The uAGT/creatinine ratios of Indigenous women with uncomplicated or complicated pregnancies were the same. A decrease in uAGT/creatinine with advancing gestational age was associated with increased urinary albumin/creatinine, as is seen in preeclampsia, but it was not specific for this disorder. The reduced uAGT/creatinine in Indigenous pregnant women may reflect subclinical renal dysfunction which limits the ability of the kidney to maintain sodium balance and could indicate an increased risk of pregnancy complications and/or future renal disease.

Ideal Cricoid Pressure Is Biomechanically Impossible During Laryngoscopy.

OBJECTIVE: This study was a prospective, randomized controlled trial of rapid sequence intubation (RSI) with cricoid pressure (CP) within the emergency department (ED). The primary aim of the study was to examine the link between ideal CP and the incidence of aspiration. METHOD: Patients > 18 years of age undergoing RSI in the ED of two hospitals in New South Wales, Australia, were randomly assigned to receive measured CP using weighing scales to target the ideal CP range (3.060-4.075 kg) or control CP where the weighing scales were used, but the CP operator was blinded to the amount of CP applied during the RSI. A data logger recorded all CP delivered during each RSI. Immediately after intubation, tracheal and esophageal samples were taken and underwent pepsin analysis. RESULTS: Fifty-four RSIs were analyzed (25 measured/29 control). Macroscopic contamination of the larynx at RSI was observed in 14 patients (26%). During induction (0-50 seconds), both groups delivered in-range CP. During intubation (51-223 seconds), laryngoscopy was associated with a reduction in mean CP below 3.060 kg in both groups. When compared, there was no statistically significant difference between the groups. For 11 patients, pepsin was detected in the oropharyngeal sample, while three were positive for tracheal pepsin. Seven patients (four control/three measured) were treated for clinical aspiration during hospitalization. As a result of the finding that neither group could maintain ideal range CP during laryngoscopy, the trial was abandoned. CONCLUSION: Laryngoscopy provides a counter force to CP, which is negated to facilitate tracheal intubation. The concept that a static 3.060 to 4.075 kg CP could be maintained during laryngoscopy and intubation was rejected by our study. Whether a lower CP range could prevent aspiration during RSI was not explored by this study.

Reference Intervals for Non-Fasting CVD Lipids and Inflammation Markers in Pregnant Indigenous Australian Women.

Indigenous Australians experience high rates of cardiovascular disease (CVD). The origins of CVD may commence during pregnancy, yet few serum reference values for CVD biomarkers exist specific to the pregnancy period. The Gomeroi gaaynggal research project is a program that undertakes research and provides some health services to pregnant Indigenous women. Three hundred and ninety-nine non-fasting samples provided by the study participants (206 pregnancies and 175 women) have been used to construct reference intervals for CVD biomarkers during this critical time. A pragmatic design was used, in that women were not excluded for the presence of chronic or acute health states. Percentile bands for non-linear relationships were constructed according to the methods of Wright and Royston (2008), using the xriml package in StataIC 13.1. Serum cholesterol, triglycerides, cystatin-C and alkaline phosphatase increased as gestational age progressed, with little change seen in high-sensitivity C-Reactive Protein and γ glutamyl transferase. Values provided in the reference intervals are consistent with findings from other research projects. These reference intervals will form a basis with which future CVD biomarkers for pregnant Indigenous Australian women can be compared.

PP025. Measurement of the activity of the circulating and intrarenal renin-angiotensin system (iRAS) in pregnant and non-pregnant subjects.

OBJECTIVES: To see if urinary angiotensinogen (uAGT)/creatinine and other urinary components of the RAS could be used to detect renal disease in pregnancy, as renal disease predisposes to preeclampsia. METHODS: Plasma and urinary prorenin, ACE and AGT (iRAS) were measured by ELISA. Urinary active renin levels were measured enzymatically (9 males, 10 non pregnant, 61 Australian Indigenous pregnant women). RESULTS: No relationships between plasma RAS and iRAS were found. In non-pregnant females plasma AGT levels were inversely related to protein and albumin/creatinine (r=-0.72, P=0.019, n=10; r=-0.65, P=0.042, n=10). In pregnancy, plasma ACE levels were related to protein/creatinine (r=0.29, P=0.036, n=54). Urinary protein/creatinine was not related to iRAS activity (males and non-pregnant females) but in pregnancy was related to prorenin and active renin/creatinine (r=0.45, P=0.02, n=26 r=0.47, P<0.001, n=50). Urinary albumin/creatinine was related to uAGT and active renin/creatinine in pregnancy (r=0.39, P=0.005, n=51; r=0.37, P=0.008, n=51). uACE/creatinine and uAGT/creatinine were related (r=0.52, P<0.001, n=51). CONCLUSION: Excretion of components of the iRAS is independent of plasma levels. Not only is uAGT/creatinine related to albumin/creatinine but there are similar relationships with other iRAS components. Measurement of the iRAS in human pregnancy may detect early stage renal disease, endemic in Indigenous Australians.

PP036. The intrarenal renin-angiotensin system and pregnancy outcome.

OBJECTIVES: The intrarenal renin angiotensin system (iRAS) may be activated in normal pregnancy. Failure of activation may predispose to preeclampsia. METHODS: Urinary angiotensinogen/creatinine (uAGT/creat), albumin and protein/creat were measured in 10 non-pregnant and 17 pregnant non-Indigenous women and 61 Indigenous pregnant women (in whom other components of iRAS were also measured). RESULTS: uAGT/creat was higher in pregnancy (18.2±3.2µg/mmol, n=9 vs. 1.1±0.3µg/mmol, P=0.001, n=10). Women with clinical proteinuria and/or preeclampsia had low uAGT/creat (n=3). Hypertensive women had normal high uAGT/creat (n=4). Indigenous pregnant women had higher protein/creat (P=0.01) and lower uAGT/creat (2.9±1.0µg/mmol, P=0.010, n=51) than non-Indigenous pregnant women. Indigenous women were classified based on a uAGT/creat of <2µg/mmol (n=37) or >2.0µg/mmol (n=12). Only low uAGT/creat Indigenous pregnant women had correlations between uAGT/creat and albumin/creat (r=0.367, P=0.027), renin/creat and albumin or protein/creat (r=0.493, P=0.002, r=0.603, P<0.001). uAGT/creat levels fell with gestation (r=-0.329, P=0.047) while Cystatin C increased (r=0.592, P=0.000). CONCLUSION: The iRAS is activated in normal pregnancy. This is not the case in women with proteinuria/preeclampsia or in many Indigenous women who have higher urinary protein/creat. Therefore a low uAGT/creat in pregnancy may indicate impaired renal function and be associated with an increased risk of preeclampsia.

Effectiveness of cricoid pressure in preventing gastric aspiration during rapid sequence intubation in the emergency department: study protocol for a randomised controlled trial.

BACKGROUND: Cricoid pressure is considered to be the gold standard means of preventing aspiration of gastric content during Rapid Sequence Intubation (RSI). Its effectiveness has only been demonstrated in cadaveric studies and case reports. No randomised controlled trials comparing the incidence of gastric aspiration following emergent RSI, with or without cricoid pressure, have been performed. If improperly applied, cricoid pressure increases risk to the patient. The clinical significance of aspiration in the emergency department is unknown. This randomised controlled trial aims to; 1. Compare the application of the 'ideal" amount of force (30 - 40 newtons) to standard, unmeasured cricoid pressure and 2. Determine the incidence of clinically defined aspiration syndromes following RSI using a fibrinogen degradation assay previously described. METHODS/DESIGN: 212 patients requiring emergency intubation will be randomly allocated to either control (unmeasured cricoid pressure) or intervention groups (30 - 40 newtons cricoid pressure). The primary outcome is the rate of aspiration of gastric contents (determined by pepsin detection in the oropharyngeal/tracheal aspirates or treatment for aspiration pneumonitis up to 28 days post-intubation). Secondary outcomes are; correlation between aspiration and lowest pre-intubation Glasgow Coma Score, the relationship between detection of pepsin in trachea and development of aspiration syndromes, complications associated with intubation and grade of the view on direct largyngoscopy. DISCUSSION: The benefits and risks of cricoid pressure application will be scrutinised by comparison of the incidence of aspiration and difficult or failed intubations in each group. The role of cricoid pressure in RSI in the emergency department and the use of a pepsin detection as a predictor of clinical aspiration will be evaluated. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry (ANZCTR): ACTRN12611000587909.