First trimester risk of preeclampsia and rate of spontaneous birth in patients without preeclampsia.

BACKGROUND: First-trimester screening for preeclampsia using a combination of maternal risk factors and mean arterial pressure, uterine artery pulsatility index, and placental growth factor, as proposed by the Fetal Medicine Foundation, provides effective prediction of preterm preeclampsia. Placental dysfunction is a potential precursor of spontaneous birth. OBJECTIVE: The objective of this study was to examine if the estimated risk of preeclampsia is associated with the gestational age at onset of spontaneous delivery in the absence of preeclampsia. STUDY DESIGN: This was a secondary analysis of the data from the Screening programme for pre-eclampsia trial in which there was a comparison of the performance of first-trimester screening for preterm preeclampsia using the Fetal Medicine Foundation model vs a traditional history-based risk scoring system. A subgroup of women from the trial with spontaneous onset of delivery (labor with intact membranes or preterm prelabor rupture of membranes) was included in this study and was arbitrarily divided into 3 groups according to the risk for preterm preeclampsia as determined by the Fetal Medicine Foundation model at 11 to 13 weeks' gestation as follows: group 1 low risk (˂1/100); group 2 intermediate risk (1/50 to 1/100); and group 3 high risk (˃1/50). A survival analysis was carried out using a Kaplan-Meier estimator and a Cox regression analysis with stratification by the 3 preeclampsia risk groups. Occurrence of spontaneous birth in the study groups was compared using log-rank tests and hazard ratios. RESULTS: The study population comprised 10,820 cases with delivery after spontaneous onset of labor among the 16,451 cases who participated in the Screening programme for pre-eclampsia trial. There were 9795 cases in group 1, 583 in group 2, and 442 in group 3. The gestational age at delivery was <28, <32, <35, <37, and <40 weeks in 0.29%, 0.64%, 1.68%, 4.52%, and 44.97% of cases, respectively, in group 1; 0.69%, 1.71%, 3.26%, 7.72%, and 55.23% of cases, respectively, in group 2; and 0.45%, 1.81%, 5.66%, 13.80%, and 63.12% of cases, respectively, in group 3. The curve profile of gestational age at spontaneous birth in the 3 study groups was significantly different overall and in pairwise comparisons (P values <.001). The Cox regression analysis showed that risks increased for spontaneous birth by 18% when the intermediate-risk group was compared with the low-risk group (P˂.001) and by 41% when the high-risk group was compared with the low-risk group (P˂.001). CONCLUSION: In this study that investigated birth after spontaneous onset of labor in women without preeclampsia, there were 2 major findings. First, the duration of pregnancy decreased with increasing first-trimester risk for preeclampsia. Second, in the high-risk group, when compared with the low-risk group, the risk for spontaneous birth was 4 times higher at a gestational age of 24 to 26 weeks, 3 times higher at 28 to 32 weeks, and 2 times higher at 34 to 39 weeks. These differences present major clinical implications for antepartum counselling, monitoring, and interventions in these pregnancies.

First-trimester prediction of preterm pre-eclampsia and prophylaxis by aspirin: Effect on spontaneous and iatrogenic preterm birth.

OBJECTIVE: To report the predictive performance for preterm birth (PTB) of the Fetal Medicine Foundation (FMF) triple test and National Institute for health and Care Excellence (NICE) guidelines used to screen for pre-eclampsia and examine the impact of aspirin in the prevention of PTB. DESIGN: Secondary analysis of data from the SPREE study and the ASPRE trial. SETTING: Multicentre studies. POPULATION: In SPREE, women with singleton pregnancies had screening for preterm pre-eclampsia at 11-13 weeks of gestation by the FMF method and NICE guidelines. There were 16 451 pregnancies that resulted in delivery at ≥24 weeks of gestation and these data were used to derive the predictive performance for PTB of the two methods of screening. The results from the ASPRE trial were used to examine the effect of aspirin in the prevention of PTB in the population from SPREE. METHODS: Comparison of performance of FMF method and NICE guidelines for pre-eclampsia in the prediction of PTB and use of aspirin in prevention of PTB. MAIN OUTCOME MEASURE: Spontaneous PTB (sPTB), iatrogenic PTB for pre-eclampsia (iPTB-PE) and iatrogenic PTB for reasons other than pre-eclampsia (iPTB-noPE). RESULTS: Estimated incidence rates of sPTB, iPTB-PE and iPTB-noPE were 3.4%, 0.8% and 1.6%, respectively. The corresponding detection rates were 17%, 82% and 25% for the triple test and 12%, 39% and 19% for NICE guidelines, using the same overall screen positive rate of 10.2%. The estimated proportions prevented by aspirin were 14%, 65% and 0%, respectively. CONCLUSION: Prediction of sPTB and iPTB-noPE by the triple test was poor and poorer by the NICE guidelines. Neither sPTB nor iPTB-noPE was reduced substantially by aspirin.

Performance of machine-learning approach for prediction of pre-eclampsia in a middle-income country.

OBJECTIVE: Pre-eclampsia (PE) is a serious complication of pregnancy associated with maternal and fetal morbidity and mortality. As current prediction models have limitations and may not be applicable in resource-limited settings, we aimed to develop a machine-learning (ML) algorithm that offers a potential solution for developing accurate and efficient first-trimester prediction of PE. METHODS: We conducted a prospective cohort study in Mexico City, Mexico to develop a first-trimester prediction model for preterm PE (pPE) using ML. Maternal characteristics and locally derived multiples of the median (MoM) values for mean arterial pressure, uterine artery pulsatility index and serum placental growth factor were used for variable selection. The dataset was split into training, validation and test sets. An elastic-net method was employed for predictor selection, and model performance was evaluated using area under the receiver-operating-characteristics curve (AUC) and detection rates (DR) at 10% false-positive rates (FPR). RESULTS: The final analysis included 3050 pregnant women, of whom 124 (4.07%) developed PE. The ML model showed good performance, with AUCs of 0.897, 0.963 and 0.778 for pPE, early-onset PE (ePE) and any type of PE (all-PE), respectively. The DRs at 10% FPR were 76.5%, 88.2% and 50.1% for pPE, ePE and all-PE, respectively. CONCLUSIONS: Our ML model demonstrated high accuracy in predicting pPE and ePE using first-trimester maternal characteristics and locally derived MoM. The model may provide an efficient and accessible tool for early prediction of PE, facilitating timely intervention and improved maternal and fetal outcome. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Eficiencia de un enfoque de aprendizaje automático para la predicción de la preeclampsia en un país de ingresos medios OBJETIVO: La preeclampsia (PE) es una complicación grave del embarazo asociada a morbilidad y mortalidad materna y del feto. Dado que los modelos de predicción actuales tienen limitaciones y pueden no ser aplicables en situaciones con recursos limitados, se propuso desarrollar un algoritmo de aprendizaje automático (AA) que ofrezca una solución con potencial para desarrollar una predicción precisa y eficiente de la PE en el primer trimestre. MÉTODOS: Se realizó un estudio de cohorte prospectivo en Ciudad de México para desarrollar un modelo de predicción de la PE pretérmino (PEp) en el primer trimestre utilizando AA. Para la selección de variables se utilizaron las características maternas y los múltiplos de la mediana (MdM) obtenidos localmente para la presión arterial media, el índice de pulsatilidad de la arteria uterina y el factor de crecimiento placentario sérico. El conjunto de datos se dividió en subconjuntos de datos de entrenamiento, de validación y de test estadístico. Se empleó un método de red elástica para la selección de predictores, y el rendimiento del modelo se evaluó mediante el área bajo la curva de características operativas del receptor (ABC) y las tasas de detección (TD) con tasas de falsos positivos (TFP) del 10%. RESULTADOS: El análisis final incluyó a 3050 mujeres embarazadas, de las cuales 124 (4,07%) desarrollaron PE. El modelo de AA mostró una buena eficiencia, con un ABC de 0,897, 0,963 y 0,778 para la PEp, la PE de aparición temprana (PEat) y cualquier tipo de PE (todas las PE), respectivamente. Las TD con TFP del 10% fueron del 76,5%, 88,2% y 50,1% para la PEp, PEat y todas las PE, respectivamente. CONCLUSIONES: Nuestro modelo de AA demostró una alta precisión en la predicción de la PEp y la PEat utilizando características maternas del primer trimestre y MdM calculados localmente. El modelo puede proporcionar una herramienta eficiente y accesible para la predicción temprana de la PE, facilitando la intervención oportuna y la mejora de los resultados maternos y del feto.

Maternal cardiovascular function in midgestation is related to placental angiogenesis.

OBJECTIVE: To investigate whether angiogenic markers of placental function are associated with maternal cardiac function and hemodynamic responses at 19-23 weeks' gestation, controlling for maternal risk factors and pregnancy complications. METHODS: This was a prospective study of women with singleton pregnancy attending King's College Hospital, London, UK, for a routine hospital visit at 19-23 weeks' gestation. We recorded maternal characteristics and measured mean arterial pressure (MAP), maternal heart rate, serum placental growth factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFlt-1). We also performed maternal echocardiography to assess cardiac output and peripheral vascular resistance as well as indices of diastolic and systolic function. RESULTS: Our cohort included 4006 women. Lower PlGF values were significantly associated with higher MAP (P < 0.0001), lower maternal heart rate (P < 0.0001), lower mitral valve s' mean velocity (P = 0.027) and higher left atrial area (P = 0.022) after adjustment for maternal characteristics and pregnancy complications. sFlt-1 was associated positively with relative wall thickness (P = 0.012), whereas sFlt-1/PlGF ratio was associated negatively with mitral valve A (P = 0.006) and positively with left atrial area (P = 0.015) and MAP (P = 0.004). The magnitude of these associations was similar in the subgroup of women without any risk factors based on their obstetric and medical history. CONCLUSIONS: A continuous association of moderate strength between angiogenic factors and subclinical maternal cardiac function alterations is present in midgestation, independently of pre-existing maternal risk factors and pregnancy complications. Impaired placental function appears to be related to mild systolic and diastolic dysfunction and cardiac remodeling. © 2024 International Society of Ultrasound in Obstetrics and Gynecology.

Evaluation of screening performance of first-trimester competing-risks prediction model for small-for-gestational age in Asian population.

OBJECTIVE: To examine the external validity of the Fetal Medicine Foundation (FMF) competing-risks model for the prediction of small-for-gestational age (SGA) at 11-14 weeks' gestation in an Asian population. METHODS: This was a secondary analysis of a multicenter prospective cohort study in 10 120 women with a singleton pregnancy undergoing routine assessment at 11-14 weeks' gestation. We applied the FMF competing-risks model for the first-trimester prediction of SGA, combining maternal characteristics and medical history with measurements of mean arterial pressure (MAP), uterine artery pulsatility index (UtA-PI) and serum placental growth factor (PlGF) concentration. We calculated risks for different cut-offs of birth-weight percentile (< 10th , < 5th or < 3rd percentile) and gestational age at delivery (< 37 weeks (preterm SGA) or SGA at any gestational age). Predictive performance was examined in terms of discrimination and calibration. RESULTS: The predictive performance of the competing-risks model for SGA was similar to that reported in the original FMF study. Specifically, the combination of maternal factors with MAP, UtA-PI and PlGF yielded the best performance for the prediction of preterm SGA with birth weight < 10th percentile (SGA < 10th ) and preterm SGA with birth weight < 5th percentile (SGA < 5th ), with areas under the receiver-operating-characteristics curve (AUCs) of 0.765 (95% CI, 0.720-0.809) and 0.789 (95% CI, 0.736-0.841), respectively. Combining maternal factors with MAP and PlGF yielded the best model for predicting preterm SGA with birth weight < 3rd percentile (SGA < 3rd ) (AUC, 0.797 (95% CI, 0.744-0.850)). After excluding cases with pre-eclampsia, the combination of maternal factors with MAP, UtA-PI and PlGF yielded the best performance for the prediction of preterm SGA < 10th and preterm SGA < 5th , with AUCs of 0.743 (95% CI, 0.691-0.795) and 0.762 (95% CI, 0.700-0.824), respectively. However, the best model for predicting preterm SGA < 3rd without pre-eclampsia was the combination of maternal factors and PlGF (AUC, 0.786 (95% CI, 0.723-0.849)). The FMF competing-risks model including maternal factors, MAP, UtA-PI and PlGF achieved detection rates of 42.2%, 47.3% and 48.1%, at a fixed false-positive rate of 10%, for the prediction of preterm SGA < 10th , preterm SGA < 5th and preterm SGA < 3rd , respectively. The calibration of the model was satisfactory. CONCLUSION: The screening performance of the FMF first-trimester competing-risks model for SGA in a large, independent cohort of Asian women is comparable with that reported in the original FMF study in a mixed European population. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Validation of machine-learning model for first-trimester prediction of pre-eclampsia using cohort from PREVAL study.

OBJECTIVE: Effective first-trimester screening for pre-eclampsia (PE) can be achieved using a competing-risks model that combines risk factors from the maternal history with multiples of the median (MoM) values of biomarkers. A new model using artificial intelligence through machine-learning methods has been shown to achieve similar screening performance without the need for conversion of raw data of biomarkers into MoM. This study aimed to investigate whether this model can be used across populations without specific adaptations. METHODS: Previously, a machine-learning model derived with the use of a fully connected neural network for first-trimester prediction of early (< 34 weeks), preterm (< 37 weeks) and all PE was developed and tested in a cohort of pregnant women in the UK. The model was based on maternal risk factors and mean arterial blood pressure (MAP), uterine artery pulsatility index (UtA-PI), placental growth factor (PlGF) and pregnancy-associated plasma protein-A (PAPP-A). In this study, the model was applied to a dataset of 10 110 singleton pregnancies examined in Spain who participated in the first-trimester PE validation (PREVAL) study, in which first-trimester screening for PE was carried out using the Fetal Medicine Foundation (FMF) competing-risks model. The performance of screening was assessed by examining the area under the receiver-operating-characteristics curve (AUC) and detection rate (DR) at a 10% screen-positive rate (SPR). These indices were compared with those derived from the application of the FMF competing-risks model. The performance of screening was poor if no adjustment was made for the analyzer used to measure PlGF, which was different in the UK and Spain. Therefore, adjustment for the analyzer used was performed using simple linear regression. RESULTS: The DRs at 10% SPR for early, preterm and all PE with the machine-learning model were 84.4% (95% CI, 67.2-94.7%), 77.8% (95% CI, 66.4-86.7%) and 55.7% (95% CI, 49.0-62.2%), respectively, with the corresponding AUCs of 0.920 (95% CI, 0.864-0.975), 0.913 (95% CI, 0.882-0.944) and 0.846 (95% CI, 0.820-0.872). This performance was achieved with the use of three of the biomarkers (MAP, UtA-PI and PlGF); inclusion of PAPP-A did not provide significant improvement in DR. The machine-learning model had similar performance to that achieved by the FMF competing-risks model (DR at 10% SPR, 82.7% (95% CI, 69.6-95.8%) for early PE, 72.7% (95% CI, 62.9-82.6%) for preterm PE and 55.1% (95% CI, 48.8-61.4%) for all PE) without requiring specific adaptations to the population. CONCLUSIONS: A machine-learning model for first-trimester prediction of PE based on a neural network provides effective screening for PE that can be applied in different populations. However, before doing so, it is essential to make adjustments for the analyzer used for biochemical testing. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.

Screening for pre-eclampsia by maternal serum glycosylated fibronectin and angiogenic markers at 36 weeks' gestation.

OBJECTIVES: First, to examine the predictive performance of maternal serum glycosylated fibronectin (GlyFn) at 35 + 0 to 36 + 6 weeks' gestation in screening for delivery with pre-eclampsia (PE) and delivery with gestational hypertension (GH) at ≥ 37 weeks' gestation, both within 3 weeks and at any time after the examination. Second, to compare the predictive performance for delivery with PE and delivery with GH of various combinations of biomarkers, including GlyFn, mean arterial pressure (MAP), uterine artery pulsatility index (UtA-PI), serum placental growth factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFlt-1). Third, to compare the predictive performance for delivery with PE and delivery with GH by serum PlGF concentration, sFlt-1/PlGF concentration ratio and the competing-risks model with different combinations of biomarkers as above. Fourth, to compare the predictive performance of screening at 11 + 0 to 13 + 6 weeks vs 35 + 0 to 36 + 6 weeks for delivery with PE and delivery with GH at ≥ 37 weeks' gestation. METHODS: This was a case-control study in which maternal serum GlyFn was measured in stored samples from a non-intervention screening study in singleton pregnancies at 35 + 0 to 36 + 6 weeks' gestation using a point-of-care device. We used samples from women who delivered at ≥ 37 weeks' gestation, including 100 who developed PE, 100 who developed GH and 600 controls who did not develop PE or GH. In all cases, MAP, UtA-PI, PlGF and sFlt-1 were measured during the routine visit at 35 + 0 to 36 + 6 weeks. We used samples from patients that had been examined previously at 11 + 0 to 13 + 6 weeks' gestation. Levels of GlyFn were transformed to multiples of the expected median (MoM) values after adjusting for maternal demographic characteristics and elements from the medical history. Similarly, the measured values of MAP, UtA-PI, PlGF and sFlt-1 were converted to MoM. The competing-risks model was used to combine the prior distribution of the gestational age at delivery with PE, obtained from maternal risk factors, with various combinations of biomarker MoM values to derive the patient-specific risks of delivery with PE. The performance of screening of different strategies was estimated by examining the detection rate (DR) at a 10% fixed false-positive rate (FPR) and McNemar's test was used to compare the DRs between the different methods of screening. RESULTS: The DR, at 10% FPR, of screening by the triple test (maternal risk factors plus MAP, PlGF and sFlt-1) was 83.7% (95% CI, 70.3-92.7%) for delivery with PE within 3 weeks of screening and 80.0% (95% CI, 70.8-87.3%) for delivery with PE at any time after screening, and this performance was not improved by the addition of GlyFn. The performance of screening by a combination of maternal risk factors, MAP, PlGF and GlyFn was similar to that of the triple test, both for delivery with PE within 3 weeks and at any time after screening. The performance of screening by a combination of maternal risk factors, MAP, UtA-PI and GlyFn was similar to that of the triple test, and they were both superior to screening by low PlGF concentration (PE within 3 weeks: DR, 65.3% (95% CI, 50.4-78.3%); PE at any time: DR, 56.0% (95% CI, 45.7-65.9%)) or high sFlt-1/PlGF concentration ratio (PE within 3 weeks: DR, 73.5% (95% CI, 58.9-85.1%); PE at any time: DR, 63.0% (95% CI, 52.8-72.4%)). The predictive performance of screening at 35 + 0 to 36 + 6 weeks' gestation for delivery with PE and delivery with GH at ≥ 37 weeks' gestation was by far superior to screening at 11 + 0 to 13 + 6 weeks. CONCLUSION: GlyFn is a potentially useful biomarker in third-trimester screening for term PE and term GH, but the findings of this case-control study need to be validated by prospective screening studies. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.

Noradrenaline-induced changes in cerebral blood flow in health, traumatic brain injury and critical illness: a systematic review with meta-analysis.

BACKGROUND: Noradrenaline is a standard treatment for hypotension in acute care. The precise effects of noradrenaline on cerebral blood flow in health and disease remain unclear. METHODS: We systematically reviewed and synthesised data from studies examining changes in cerebral blood flow in healthy participants and patients with traumatic brain injury and critical illness. RESULTS: Twenty-eight eligible studies were included. In healthy subjects and patients without critical illness or traumatic brain injury, noradrenaline did not significantly change cerebral blood flow velocity (-1.7%, 95%CI -4.7-1.3%) despite a 24.1% (95%CI 19.4-28.7%) increase in mean arterial pressure. In patients with traumatic brain injury, noradrenaline significantly increased cerebral blood flow velocity (21.5%, 95%CI 11.0-32.0%), along with a 33.8% (95%CI 14.7-52.9%) increase in mean arterial pressure. In patients who were critically ill, noradrenaline significantly increased cerebral blood flow velocity (20.0%, 95%CI 9.7-30.3%), along with a 32.4% (95%CI 25.0-39.9%) increase in mean arterial pressure. Our analyses suggest intact cerebral autoregulation in healthy subjects and patients without critical illness or traumatic brain injury., and impaired cerebral autoregulation in patients with traumatic brain injury and who were critically ill. The extent of mean arterial pressure changes and the pre-treatment blood pressure levels may affect the magnitude of cerebral blood flow changes. Studies assessing cerebral blood flow using non-transcranial Doppler methods were inadequate and heterogeneous in enabling meaningful meta-analysis. CONCLUSIONS: Noradrenaline significantly increases cerebral blood flow in humans with impaired, not intact, cerebral autoregulation, with the extent of changes related to the severity of functional impairment, the extent of mean arterial pressure changes and pre-treatment blood pressure levels.

Influence of antibiotic therapy with hemodynamic optimization on 30-day mortality among septic shock patients cared for in the prehospital setting.

BACKGROUND: In order to reduce septic shock mortality, international guidelines recommend early treatment implementation, antibiotic therapy (ABT) and hemodynamic optimisation, within 1-h. This retrospective multicentric study aims to investigate the relationship between prehospital ABT delivered within 1st hour and mean blood pressure (MAP) ≥ 65 mmHg at the end of the prehospital stage, and 30-day mortality among patients with septic shock. METHODS: From May 2016 to December 2021, patients with septic shock requiring pre-hospital Mobile Intensive Care Unit intervention (MICU) were retrospectively analysed. To assess the relationship between 30-day mortality and prehospital ABT delivered within 1st hour and/or MAP ≥ 65 mmHg at the end of the prehospital stage, Inverse Probability Treatment Weighting (IPTW) propensity score method was performed. RESULTS: Among the 530 patients included, 341 were male gender (64%) with a mean age of 69 ± 15 years. One-hundred and thirty-two patients (25%) patients received prehospital ABT, among which 98 patients (74%) were treated with 3rd generation cephalosporin. Suspected pulmonary, urinary and digestive infections were the cause of sepsis in respectively 43%, 25% and 17%. The 30-day overall mortality was 31%. A significant association was observed between 30-day mortality rate and (i) ABT administration within the first hour: RRa = 0.14 [0.04-0.55], (ii) ABT administration within the first hour associated with a MAP ≥ 65 mmHg: RRa = 0.08 [0.02-0.37] and (iii) ABT administration within the first hour in the prehospital setting associated with a MAP < 65 mmHg at the end of the prehospital stage: RRa = 0.75 [0.45-0.85]. Patients who received prehospital ABT after the first hour have also a 30-day mortality rate decrease: RRa = 0.87 [0.57-0.99], whereas patients who did not received ABT had an increased 30-day mortality rate: RRa = 2.36 [1.89-2.95]. CONCLUSION: In this study, we showed that pre-hospital ABT within the first hour and MAP≥65 mmHg at the end of prehospital stage are both associated with 30-day mortality decrease among patients suffering from septic shock cared for by a MICU. Further prospective studies are needed to confirm these preliminary results.

Association between low values of mean arterial pressure and impaired cognitive performance in older patients with mild cognitive impairment: cross-sectional preliminary findings from the STRENGTH Project.

BACKGROUND: Uncontrolled blood pressure (BP) is a risk factor for Mild Cognitive Impairment (MCI) and dementia. AIMS: This study examined the relationship between BP and clinical/cognitive/neuropsychological aspects in MCI individuals. METHODS: MCI patients underwent clinical, functional, cognitive and metacognitive, as well as psychological assessments. Social network, lifestyle characteristics, and medication prescriptions were also evaluated. Each patient underwent BP measurements. RESULTS: Lower values of systolic BP (SBP), diastolic BP (DBP), and mean arterial pressure (MAP) were associated with poorer cognitive performance. Notably, MAP showed greater capability in detecting impairments in attention and visuospatial abilities compared to SBP and DBP. DISCUSSION: These findings support the notion that in older individuals with MCI excessively low BP values, particularly MAP, might represent a risk and suggest that cerebral hypoperfusion may play a key role. CONCLUSIONS: Routine assessment of MAP could aid clinicians in adjusting antihypertensive treatment and closely monitoring cognitive function in MCI patients.

The Effect of Recruitment Maneuvers on Cerebrovascular Dynamics and Right Ventricular Function in Patients with Acute Brain Injury: A Single-Center Prospective Study.

BACKGROUND: Optimization of ventilatory settings is challenging for patients in the neurointensive care unit, requiring a balance between precise gas exchange control, lung protection, and managing hemodynamic effects of positive pressure ventilation. Although recruitment maneuvers (RMs) may enhance oxygenation, they could also exert profound undesirable systemic impacts. METHODS: The single-center, prospective study investigated the effects of RMs (up-titration of positive end-expiratory pressure) on multimodal neuromonitoring in patients with acute brain injury. Our primary focus was on intracranial pressure and secondarily on cerebral perfusion pressure (CPP) and other neurological parameters: cerebral autoregulation [pressure reactivity index (PRx)] and regional cerebral oxygenation (rSO2). We also assessed blood pressure and right ventricular (RV) function evaluated using tricuspid annular plane systolic excursion. Results are expressed as the difference (Δ) from baseline values obtained after completing the RMs. RESULTS: Thirty-two patients were enrolled in the study. RMs resulted in increased intracranial pressure (Δ = 4.8 mm Hg) and reduced CPP (ΔCPP = -12.8 mm Hg) and mean arterial pressure (difference in mean arterial pressure = -5.2 mm Hg) (all p < 0.001). Cerebral autoregulation worsened (ΔPRx = 0.31 a.u.; p < 0.001). Despite higher systemic oxygenation (difference in partial pressure of O2 = 4 mm Hg; p = 0.001) and unchanged carbon dioxide levels, rSO2 marginally decreased (ΔrSO2 = -0.5%; p = 0.031), with a significant drop in arterial content and increase in the venous content. RV systolic function decreased (difference in tricuspid annular plane systolic excursion = -0.1 cm; p < 0.001) with a tendency toward increased RV basal diameter (p = 0.06). Grouping patients according to ΔCPP or ΔPRx revealed that those with poorer tolerance to RMs had higher CPP (p = 0.040) and a larger RV basal diameter (p = 0.034) at baseline. CONCLUSIONS: In patients with acute brain injury, RMs appear to have adverse effects on cerebral hemodynamics. These findings might be partially explained by RM's impact on RV function. Further advanced echocardiography monitoring is required to prove this hypothesis.

Predicting sepsis at emergency department triage: Implementing clinical and laboratory markers within the first nursing assessment to enhance diagnostic accuracy.

BACKGROUND: Early identification of sepsis in the emergency department (ED) triage is both valuable and challenging. Numerous studies have endeavored to pinpoint clinical and biochemical criteria to assist clinicians in the prompt diagnosis of sepsis, but few studies have assessed the efficacy of these criteria in the ED triage setting. The aim of the study was to explore the accuracy of clinical and laboratory markers evaluated at the triage level in identifying patients with sepsis. METHODS: A prospective study was conducted in a large academic urban hospital, implementing a triage protocol aimed at early identification of septic patients based on clinical and laboratory markers. A multidisciplinary panel of experts reviewed cases to ensure accurate identification of septic patients. Variables analyzed included: Charlson comorbidity index, mean arterial pressure (MAP), partial pressure of carbon dioxide (PetCO2), white cell count, eosinophil count, C-reactive protein to albumin ratio, procalcitonin, and lactate. RESULTS: A total of 235 patients were included. Multivariable analysis identified procalcitonin ≥1 ng/mL (OR 5.2; p < 0.001); CRP-to-albumin ratio ≥32 (OR 6.6; p < 0.001); PetCO2 ≤ 28 mmHg (OR 2.7; p = 0.031), and MAP <85 mmHg (OR 7.5; p < 0.001) as independent predictors for sepsis. MAP ≥85 mmHg, CRP/albumin ratio <32, and procalcitonin <1 ng/mL demonstrated negative predictive values for sepsis of 90%, 89%, and 88%, respectively. CONCLUSIONS: Our study underscores the significance of procalcitonin and mean arterial pressure, while introducing CRP/albumin ratio and PetCO2 as important variables to consider in the very initial assessment of patients with suspected sepsis in the ED. CLINICAL RELEVANCE: Early identification of sepsis since the emergency department (ED) triage is challenging Implementing the ED triage protocol with simple clinical and laboratory markers allows to recognize patients with sepsis with a very good discriminatory power (AUC 0.88).

Incidence and predictors of intraoperative hypotension during transurethral bladder tumor resection with oral 5-aminolevulinic acid.

OBJECTIVES: To analyze the incidence and risk factors of intraoperative hypotension related to photodynamic diagnosis-assisted transurethral resection of bladder tumor (PDD-TURBT) with oral 5-aminolevulinic acid (5-ALA). METHODS: We retrospectively analyzed 487 patients with bladder tumors who underwent PDD-TURBT (n = 184) or conventional TURBT (conv-TURBT) (n = 303) between 2018 and 2021. Intraoperative hypotension was defined as hypotension requiring vasopressors during TURBT, and its incidence was compared between the two groups. Potential risk factors of intraoperative hypotension, including preoperative change in mean arterial pressure (MAP), were further investigated in patients receiving PDD-TURBT. RESULTS: The median age was 72 years, 392 patients (81%) were male, and 203 (42%) had hypertension. TURBT was performed under general and spinal anesthesia in 76 (16%) and 411 (84%) patients, respectively. The incidence of intraoperative hypotension was significantly higher in PDD-TURBT compared to conv-TURBT (43% vs. 17%, respectively). The median change in MAP until the induction of anesthesia was +6.5 mmHg (range: -29.0 to +46.3) in the PDD-TURBT group and +14.7 mmHg (range: -35.3 to +67.7) in the conv-TURBT group, showing a significantly smaller increase in the PDD-TURBT group (p < 0.001). In the multivariable analysis for PDD-TURBT patients, advanced age, general anesthesia, and lower MAP change (<+6.5 mmHg) until anesthesia induction were significantly associated with intraoperative hypotension (p = 0.0104, <0.001, and <0.001, respectively). CONCLUSIONS: Intraoperative hypotension occurred more frequently in patients who underwent PDD-TURBT than in those who underwent conv-TURBT. Using oral 5-ALA decreases preoperative blood pressure elevation and may be responsible for intraoperative hypotension.

Periods of low renal perfusion pressure are associated with acute kidney injury following paediatric cardiac surgery.

INTRODUCTION: Acute kidney injury is associated with worse outcomes after cardiac surgery. The haemodynamic goals to ameliorate kidney injury are not clear. Low post-operative renal perfusion pressure has been associated with acute kidney injury in adults. Inadequate oxygen delivery may also cause kidney injury. This study evaluates pressure and oximetric haemodynamics after paediatric cardiac surgery and their association with acute kidney injury. MATERIALS AND METHODS: Retrospective case-control study at a children's hospital. Patients were < 6 months of age who underwent a Society of Thoracic Surgery-European Association for Cardio-Thoracic Surgery Congenital Heart Surgery categories ≥ 3. Low renal perfusion pressure was time and depth below several tested thresholds. The primary outcome was serum creatine-defined acute kidney injury in the first 7 days. RESULTS: Sixty-six patients (median age 8 days) were included. Acute kidney injury occurred in 36%. The time and depth of renal perfusion pressure < 42 mmHg in the first 24 hours was greater in acute kidney injury patients (94 versus 35 mmHg*minutes of low renal perfusion pressure/hour, p = 0.008). In the multivariable model, renal perfusion pressure < 42 mmHg was associated with acute kidney injury (aOR: 2.07, 95%CI: 1.25-3.82, p = 0.009). Mean arterial pressure, central venous pressure, and measures of inadequate oxygen delivery were not associated with acute kidney injury. CONCLUSION: Periods of low renal perfusion pressure (<42 mmHg) in the first 24 post-operative hours are associated with acute kidney injury. Renal perfusion pressure is a potential modifiable target that may mitigate the impact of acute kidney injury after paediatric cardiac surgery.

Three Simple Parameters on Admission to the Emergency Department are Predictors for Endoscopic Intervention in Patients with Suspected Nonvariceal Upper Gastrointestinal Bleeding.

BACKGROUND: A considerable number of patients with nonvariceal upper gastrointestinal bleeding (UGIB) need endoscopic intervention. OBJECTIVE: The aim of this study was to determine factors that predict the need for endoscopic intervention at the time of admission to the emergency department. METHODS: Consecutive patients with International Classification of Diseases, Tenth Revision diagnosis code K92.2 (gastrointestinal hemorrhage) who underwent upper endoscopy between February 2019 and February 2022, including patients diagnosed with nonvariceal UGIB in the emergency department in the study were reviewed retrospectively. The patients were divided into two groups: those treated endoscopically and those not treated endoscopically. These two groups were compared according to clinical and laboratory findings at admission and independent predictors for endoscopic intervention were determined using multivariate regression analysis. RESULTS: Although 123 patients (30.3%) were treated endoscopically, endoscopic treatment was not required in 283 (69.7%) patients. Syncope, mean arterial pressure (MAP), and blood urea nitrogen (BUN) at admission were independent predictors for endoscopic intervention in the multivariate analysis, after adjusting for endoscopy time. The area under the curve of the syncope+MAP+BUN combination for endoscopic intervention was 0.648 (95% CI 0.588-0.708). Although the syncope+MAP+BUN combination predicted the need for intervention significantly better than pre-endoscopy Rockall and AIMS65 scores (p = 0.010 and p < 0.001, respectively), there was no significant difference in its comparison with the Glasgow-Blatchford score (p = 0.103). CONCLUSIONS: Syncope, MAP, and BUN at admission were independent predictors for endoscopic therapy in patients with nonvariceal UGIB. Rather than using complicated scores, it would be more practical and easier to predict the need for endoscopic intervention with these three simple parameters, which are included in the Glasgow-Blatchford score.

Preserving flow, saving lives: Successful treatment of aortic valve failure in acute myocardial infarction without flow down-regulation using ECMO - a case report and mini review.

Direct percutaneous coronary intervention (PPCI) has significantly reduced cardiac mortality in patients with acute myocardial infarction (AMI), but the mortality rate remains high for those who develop cardiogenic shock (CS), reaching 40% to 50%. Veno-arterial extracorporeal membrane oxygenation (V-A ECMO) provides robust hemodynamic support and oxygen delivery for AMI patients with refractory CS, ensuring adequate organ perfusion and oxygen supply. However, there is currently no standardized optimal Mean Arterial Pressure (MAP) range during V-A ECMO support. Achieving the proper MAP is crucial for adequate myocardial perfusion, cardiac function recovery, successful weaning off of V-A ECMO, and improving long-term outcomes. In this case study, we successfully treated a 55-year-old man with AMI and refractory cardiogenic shock using V-A ECMO. By adjusting ECMO blood flow and employing hemodynamic strategies, including vasoactive drugs, we optimized the MAP, leading to improved cardiac function and successful weaning off of V-A ECMO. This presents a potential opportunity for MAP optimization under ECMO support in patients with acute myocardial infarction and cardiogenic shock.

Relationship between difference of preoperative and cardiopulmonary bypass mean arterial pressure, and acute kidney injury in cardiac surgical patients undergoing valve surgery.

BACKGROUND: Modifiable and non-modifiable factors contribute to development and progression of acute kidney injury (AKI) during cardiac surgery. We hypothesized that, the difference between preoperative mean arterial pressure (MAP) and the average mean arterial pressure maintained on cardiopulmonary bypass (CPB) would be strongly predictive of AKI. We also measured plasma Neutrophil gelatinase-associated lipocalin (NGAL), to establish its association with cardiac surgery associated-AKI (CSA-AKI). METHODS: One hundred and twelve high-risk patients undergoing valve, and valve plus coronary artery bypass grafting (CABG) surgery under cardiopulmonary bypass (CPB) were included in this study. Delta mean arterial pressure (MAP) was calculated as the difference between the average of pre-operative and on-bypass MAP, and blood was sampled for NGAL levels, at baseline, and 6-h after CPB. Detailed data collection was done, tabulating most of the factors which might influence development of post-operative cardiac surgery associated-AKI (CSA-AKI). To define CSA-AKI within the first 24-h post-operatively, the Kidney Disease Improving Global Outcomes (KDIGO) classification was used. RESULTS: Out of 112 patients, 44 (39.3%) developed CSA-AKI postoperatively. With an ROC analysis cut-off of delta MAP of more than 25.67 mmHg, 46.4% patients developed post-operative AKI, and the average CPB flows which were 1.8 ± 0.2 were not contributory to the development of early CSA-AKI. In our study, ELISA test for human NGAL was performed on serum samples, and the estimated cut-off value of 1661 ng/mL was found to be significantly associated with early CSA-AKI. CONCLUSIONS: Delta MAP and CPB flows are not related to early post-surgical CSA-AKI in cases with prior high-risk elements. However, baseline serum NGAL, as well as its percent change during the early post-surgical period independently predicted the development of CSA-AKI. This implies that, there may be patients with a higher pre-operative preponderance to develop this complication, which could actually be delineated by the use of serum NGAL estimations at baseline.

Renal medullary oxygenation during laparoscopic vs open surgery: the impact of blood pressure management-a pilot randomized controlled trial.

The impact of blood pressure targets and surgical approach (laparoscopic or open) on continuous urinary oxygenation (PuO2), a validated surrogate of renal medullary PO2, during general surgery, is unclear. We aimed to assess the effects of different blood pressure targets and surgical procedures on PuO2. We randomized patients receiving either laparoscopic or open surgery into two mean arterial pressure (MAP) target groups: usual MAP or a high MAP. We measured PuO2 in real-time and analyzed it according to the type of surgery and blood pressure target. The study was retrospectively registered on the 5th of July 2023 (ACTRN12623000726651). We included 43 participants who underwent either laparoscopic (n = 20) or open surgery (n = 23). We found that PuO2 significantly decreased during both laparoscopic and open surgery under a usual blood pressure target (- 51% and - 49%, respectively). However, there was a sharper fall with laparoscopic surgery resulting in a higher PuO2 with open surgery (mean difference: 11 ± 1 mmHg higher; p < 0.001). Targeting a higher MAP resulted in a higher PuO2 over time during laparoscopic surgery (mean difference: 7 ± 1 mmHg, p < 0.001). In contrast, targeting a usual MAP resulted in a higher PuO2 during open surgery (mean difference: 7 ± 1 mmHg, p < 0.001). Surgical approach and intraoperative blood pressure targets significantly impact urinary oxygenation. Further studies with larger sample sizes are needed to confirm these findings and understand their potential clinical implications.Registration number: ACTRN12623000726651; Date of registration: 05/07/2023 (retrospectively registered).

Hemodynamic goals in sepsis and septic shock resuscitation: An umbrella review of systematic reviews and meta-analyses with trial sequential analysis.

OBJECTIVE: The objective of this study was to verify whether any parameter among those used as the target for haemodynamic optimisation (e.g., mean arterial pressure, central venous oxygen saturation, systolic or diastolic dysfunction, CO2 gap, lactates, right ventricular dysfunction, and PvaCO2/CavO2 ratio) is correlated with mortality in an undifferentiated population with sepsis or septic shock. METHODS: An umbrella review, searching MEDLINE, the Cochrane Database of Systematic Reviews, Health Technology Assessment Database, and the JBI Database of Systematic Reviews and Implementation Reports, was performed. We included systematic reviews and meta-analyses enrolling a population of unselected patients with sepsis or septic shock. The main outcome was mortality. Two authors conducted data extraction and risk-of-bias assessments independently. We used a random-effects model to pool binary and continuous data and summarised estimates of effect using equivalent odds ratios (eORs). We used the ROBIS tool to assess risk of bias and the assessment of multiple systematic reviews 2 score to assess global quality. DATA SYNTHESIS: 17 systematic reviews and meta-analyses (15 828 patients) were included in the quantitative analysis. Diastolic dysfunction (eOR: 1.42; 95% confidence interval [CI]: 1.14-1.76), PvaCO2/CavO2 ratio (eOR: 2.15; 95% CI: 1.37-3.37), and CO2 gap (eOR: 1.86; 95% CI: 1.07-3.25) showed a significant correlation with mortality. Lactates were the parameter with highest inconsistency (I2 = 92%). Central venous oxygen saturation and right ventricle dysfunction showed significant statistical excess test of significance (p-value = 0.009 and 0.005, respectively). None of the considered parameters showed statistically significant publication bias. CONCLUSIONS: According to this umbrella review, diastolic dysfunction is the haemodynamic variable that is most closely linked to the prognosis of septic patients. The PvaCO2/CavO2 ratio and the CO2gap are significantly related to the mortality of septic patients, but the poor quality of evidence or the low number of cases, studied so far, limit their clinical applicability. CLINICAL TRIAL REGISTRATION: PROSPERO: International prospective register of systematic reviews, 2023, CRD42023432813 (Available from: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023432813).

Is target-controlled infusion better than manual controlled infusion during TIVA for elective neurosurgery? Results of a single-centre pilot study.

INTRODUCTION: Maintaining optimal systemic circulatory parameters is essential to ensure adequate cerebral perfusion (CPP) during neurosurgery, especially when autoregulation is impaired. AIM OF STUDY: To compare two types of total intravenous anaesthesia i.e. target controlled infusion (TCI) and manually controlled infusion (MCI) with propofol and remifentanil in terms of their control of cardiovascular parameters during neurosurgical resection of intracranial pathology. MATERIAL AND METHODS: Patients with supratentorial intracranial pathology were selected for the study. Patients in ASA grades III and IV and those with diseases of the circulatory system were excluded. Patients were randomly divided into two equal groups according to the method of general anaesthesia used i.e. TCI or MCI. During the neurosurgery, the values of mean arterial pressure (MAP), heart rate (HR), bispectral index (BIS) and central venous pressure were monitored and recorded at the designated 14 relevant (i.e. critical from the anaesthetist's and neurosurgeon's points of view) measurement points. RESULTS: Fifty patients (25 TCI and 25 MCI) were enrolled in the study. The groups did not differ with respect to sex, age and BMI, operation time or volume of removed lesions. TCI-anaesthetised patients had better MAP stability at the respective time points. CONCLUSIONS: Due to the greater stability of MAP, which has a direct effect on CPP, TCI appears to be the method of choice in anaesthesia for intracranial surgery.