Maternal vascular indices at 36 weeks' gestation in the prediction of preeclampsia.

BACKGROUND: Epidemiological studies have shown that women with preeclampsia (PE) are at increased long term cardiovascular risk. This risk might be associated with accelerated vascular ageing process but data on vascular abnormalities in women with PE are scarce. OBJECTIVE: This study aimed to identify the most discriminatory maternal vascular index in the prediction of PE at 35 to 37 weeks' gestation and to examine the performance of screening for PE by combinations of maternal risk factors and biophysical and biochemical markers at 35 to 37 weeks' gestation. STUDY DESIGN: This was a prospective observational nonintervention study in women attending a routine hospital visit at 35 0/7 to 36 6/7 weeks' gestation. The visit included recording of maternal demographic characteristics and medical history, vascular indices, and hemodynamic parameters obtained by a noninvasive operator-independent device (pulse wave velocity, augmentation index, cardiac output, stroke volume, central systolic and diastolic blood pressures, total peripheral resistance, and fetal heart rate), mean arterial pressure, uterine artery pulsatility index, and serum concentration of placental growth factor and soluble fms-like tyrosine kinase-1. The performance of screening for delivery with PE at any time and at <3 weeks from assessment using a combination of maternal risk factors and various combinations of biomarkers was determined. RESULTS: The study population consisted of 6746 women with singleton pregnancies, including 176 women (2.6%) who subsequently developed PE. There were 3 main findings. First, in women who developed PE, compared with those who did not, there were higher central systolic and diastolic blood pressures, pulse wave velocity, peripheral vascular resistance, and augmentation index. Second, the most discriminatory indices were systolic and diastolic blood pressures and pulse wave velocity, with poor prediction from the other indices. However, the performance of screening by a combination of maternal risk factors plus mean arterial pressure was at least as high as that of a combination of maternal risk factors plus central systolic and diastolic blood pressures; consequently, in screening for PE, pulse wave velocity, mean arterial pressure, uterine artery pulsatility index, placental growth factor, and soluble fms-like tyrosine kinase-1 were used. Third, in screening for both PE within 3 weeks and PE at any time from assessment, the detection rate at a false-positive rate of 10% of a biophysical test consisting of maternal risk factors plus mean arterial pressure, uterine artery pulsatility index, and pulse wave velocity (PE within 3 weeks: 85.2%; 95% confidence interval, 75.6%-92.1%; PE at any time: 69.9%; 95% confidence interval, 62.5%-76.6%) was not significantly different from a biochemical test using the competing risks model to combine maternal risk factors with placental growth factor and soluble fms-like tyrosine kinase-1 (PE within 3 weeks: 80.2%; 95% confidence interval, 69.9%-88.3%; PE at any time: 64.2%; 95% confidence interval, 56.6%-71.3%), and they were both superior to screening by low placental growth factor concentration (PE within 3 weeks: 53.1%; 95% confidence interval, 41.7%-64.3%; PE at any time: 44.3; 95% confidence interval, 36.8%-52.0%) or high soluble fms-like tyrosine kinase-1-to-placental growth factor concentration ratio (PE within 3 weeks: 65.4%; 95% confidence interval, 54.0%-75.7%; PE at any time: 53.4%; 95% confidence interval, 45.8%-60.9%). CONCLUSION: First, increased maternal arterial stiffness preceded the clinical onset of PE. Second, maternal pulse wave velocity at 35 to 37 weeks' gestation in combination with mean arterial pressure and uterine artery pulsatility index provided effective prediction of subsequent development of preeclampsia.

First trimester screening for pre-eclampsia and targeted aspirin prophylaxis: a cost-effectiveness cohort study.

OBJECTIVE: Investigate cost-effectiveness of first trimester pre-eclampsia screening using the Fetal Medicine Foundation (FMF) algorithm and targeted aspirin prophylaxis in comparison with standard care. DESIGN: Retrospective observational study. SETTING: London tertiary hospital. POPULATION: 5957 pregnancies screened for pre-eclampsia using the National Institute for Health and Care Excellence (NICE) method. METHODS: Differences in pregnancy outcomes between those who developed pre-eclampsia, term pre-eclampsia and preterm pre-eclampsia were compared by the Kruskal-Wallis and Chi-square tests. The FMF algorithm was applied retrospectively to the cohort. A decision analytic model was used to estimate costs and outcomes for pregnancies screened using NICE and those screened using the FMF algorithm. The decision point probabilities were calculated using the included cohort. MAIN OUTCOME MEASURES: Incremental healthcare costs and QALY gained per pregnancy screened. RESULTS: Of 5957 pregnancies, 12.8% and 15.9% were screen-positive for development of pre-eclampsia using the NICE and FMF methods, respectively. Of those who were screen-positive by NICE recommendations, aspirin was not prescribed in 25%. Across the three groups, namely, pregnancies without pre-eclampsia, term pre-eclampsia and preterm pre-eclampsia there was a statistically significant trend in rates of emergency caesarean (respectively 21%, 43% and 71.4%; P < 0.001), admission to neonatal intensive care unit (NICU) (5.9%, 9.4%, 41%; P < 0.001) and length of stay in NICU. The FMF algorithm was associated with seven fewer cases of preterm pre-eclampsia, cost saving of £9.06 and QALY gain of 0.00006/pregnancy screened. CONCLUSIONS: Using a conservative approach, application of the FMF algorithm achieved clinical benefit and an economic cost saving.

Ophthalmic artery Doppler at 36 weeks' gestation in prediction of pre-eclampsia: validation and update of previous model.

OBJECTIVE: To validate and extend a model incorporating maternal ophthalmic artery Doppler at 35-37 weeks' gestation in the prediction of subsequent development of pre-eclampsia (PE). METHODS: This was a prospective validation study of screening for PE (defined according to the 2019 American College of Obstetricians and Gynecologists criteria) by maternal ophthalmic artery peak systolic velocity (PSV) ratio in 6746 singleton pregnancies undergoing routine care at 35 + 0 to 36 + 6 weeks' gestation (validation dataset). Additionally, the data from the validation dataset were combined with those of 2287 pregnancies that were previously used for development of the model (training dataset), and the combined data were used to update the original model parameters. The competing-risks model was used to estimate the individual patient-specific risk of delivery with PE at any time and within 3 weeks from assessment by a combination of maternal demographic characteristics and medical history with PSV ratio alone and in combination with the established PE biomarkers of mean arterial pressure (MAP), uterine artery pulsatility index (UtA-PI), serum placental growth factor (PlGF) and serum soluble fms-like tyrosine kinase-1 (sFlt-1). We evaluated the predictive performance of the model by examining, first, the ability to discriminate between the PE and non-PE groups using the area under the receiver-operating-characteristics curve and the detection rate (DR) at fixed screen-positive (SPR) and false-positive rates of 10% and, second, calibration by measuring the calibration slope and calibration-in-the-large. McNemar's test was used to compare the performance of screening by a biophysical test (maternal factors, MAP, UtA-PI and PSV ratio) vs a biochemical test (maternal factors, PlGF and sFlt-1), low PlGF concentration (< 10th percentile) or high sFlt-1/PlGF concentration ratio (> 90th percentile). RESULTS: In the validation dataset, the performance of screening by maternal factors and PSV ratio for delivery with PE within 3 weeks and at any time after assessment was consistent with that in the training dataset, and there was good agreement between the predicted and observed incidence of PE. In the combined data from the training and validation datasets, good prediction for PE was achieved in screening by a combination of maternal factors, MAP, UtA-PI, PlGF, sFlt-1 and PSV ratio, with a DR, at a 10% SPR, of 85.0% (95% CI, 76.5-91.4%) for delivery with PE within 3 weeks and 65.7% (95% CI, 59.2-71.7%) for delivery with PE at any time after assessment. The performance of a biophysical test was superior to that of screening by low PlGF concentration or high sFlt-1/PlGF concentration ratio but not significantly different from the performance of a biochemical test combining maternal factors with PlGF and sFlt-1 for both PE within 3 weeks and PE at any time after assessment. CONCLUSION: Maternal ophthalmic artery PSV ratio at 35-37 weeks' gestation in combination with other biomarkers provides effective prediction of subsequent development of PE. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.

Associations between anxiety, sleep, and blood pressure parameters in pregnancy: a prospective pilot cohort study.

BACKGROUND: The potential effect modification of sleep on the relationship between anxiety and elevated blood pressure (BP) in pregnancy is understudied. We evaluated the relationship between anxiety, insomnia, and short sleep duration, as well as any interaction effects between these variables, on BP during pregnancy. METHODS: This was a prospective pilot cohort of pregnant people between 23 to 36 weeks' gestation at a single institution between 2021 and 2022. Standardized questionnaires were used to measure clinical insomnia and anxiety. Objective sleep duration was measured using a wrist-worn actigraphy device. Primary outcomes were systolic (SBP), diastolic (DBP), and mean (MAP) non-invasive BP measurements. Separate sequential multivariable linear regression models fit with generalized estimating equations (GEE) were used to separately assess associations between anxiety (independent variable) and each BP parameter (dependent variables), after adjusting for potential confounders (Model 1). Additional analyses were conducted adding insomnia and the interaction between anxiety and insomnia as independent variables (Model 2), and adding short sleep duration and the interaction between anxiety and short sleep duration as independent variables (Model 3), to evaluate any moderating effects on BP parameters. RESULTS: Among the 60 participants who completed the study, 15 (25%) screened positive for anxiety, 11 (18%) had subjective insomnia, and 34 (59%) had objective short sleep duration. In Model 1, increased anxiety was not associated with increases in any BP parameters. When subjective insomnia was included in Model 2, increased DBP and MAP was significantly associated with anxiety (DBP: ß 6.1, p = 0.01, MAP: ß 6.2 p < 0.01). When short sleep was included in Model 3, all BP parameters were significantly associated with anxiety (SBP: ß 9.6, p = 0.01, DBP: ß 8.1, p < 0.001, and MAP: ß 8.8, p < 0.001). No moderating effects were detected between insomnia and anxiety (p interactions: SBP 0.80, DBP 0.60, MAP 0.32) or between short sleep duration and anxiety (p interactions: SBP 0.12, DBP 0.24, MAP 0.13) on BP. CONCLUSIONS: When including either subjective insomnia or objective short sleep duration, pregnant people with anxiety had 5.1-9.6 mmHg higher SBP, 6.1-8.1 mmHg higher DBP, and 6.2-8.8 mmHg higher MAP than people without anxiety.

Cerebral autoregulation-based mean arterial pressure targets and delirium in critically ill adults without brain injury: a retrospective cohort study.

PURPOSE: Cerebral autoregulation (CA) is a mechanism that acts to maintain consistent cerebral perfusion across a range of blood pressures, and impaired CA is associated with delirium. Individualized CA-derived blood pressure targets are poorly characterized in critically ill patients and the association with intensive care unit (ICU) delirium is unknown. Our objectives were to characterize optimal mean arterial pressure (MAPopt) ranges in critically ill adults without brain injury and determine whether deviations from these targets contribute to ICU delirium. METHODS: We performed a retrospective cohort analysis of patients with shock of any etiology and/or respiratory failure requiring invasive mechanical ventilation, without a neurologic admitting diagnosis. Patients were screened daily for delirium. Cerebral oximetry and mean arterial pressure data were captured for the first 24 hr from enrolment. RESULTS: Forty-two patients with invasive blood pressure monitoring data were analyzed. Optimal mean arterial pressure targets ranged from 55 to 100 mm Hg. Optimal mean arterial pressure values were not significantly different based on history of hypertension or delirium status, and delirium was not associated with deviations from MAPopt. Nevertheless, the majority (69%) of blood pressure targets exceeded the current 65 mm Hg Surviving Sepsis guidelines. CONCLUSION: We observed that MAPopt targets across patients were highly variable, but did not observe an association with the incidence of delirium. Studies designed to evaluate the impact on neurologic outcomes are needed to understand the association with individualized mean arterial pressure targets in the ICU. STUDY REGISTRATION: ClinicalTrials.gov (NCT02344043); first submitted 22 January 2015.

RéSUMé: OBJECTIF: L'autorégulation cérébrale (AC) est un mécanisme qui agit pour maintenir une perfusion cérébrale constante pour une gamme de tensions artérielles, et une altération de l'AC est associée au delirium. Les cibles de tension artérielle individualisées dérivées de l'AC sont mal caractérisées chez les patient·es gravement malades et l'association avec le delirium à l'unité de soins intensifs (USI) est inconnue. Nos objectifs étaient de caractériser la tension artérielle moyenne optimale (TAMopt) chez les adultes gravement malades sans lésion cérébrale et de déterminer si les écarts par rapport à ces cibles contribuaient au delirium à l'USI. MéTHODE: Nous avons réalisé une analyse de cohorte rétrospective de patient·es présentant un choc de toute étiologie et/ou une insuffisance respiratoire nécessitant une ventilation mécanique invasive, et n'ayant pas reçu de diagnostic d'atteinte neurologique à l'admission. Les patients ont été dépistés quotidiennement pour le delirium. Les données d'oxymétrie cérébrale et de tension artérielle moyenne ont été saisies pendant les 24 premières heures suivant le recrutement. RéSULTATS: Quarante-deux patient·es pour qui des données de monitorage invasif de la tension artérielle étaient disponibles ont été analysé·es. Les cibles optimales de tension artérielle moyenne variaient de 55 à 100 mm Hg. Les valeurs optimales de tension artérielle moyenne n'étaient pas significativement différentes en fonction des antécédents d'hypertension ou de delirium, et le delirium n'était pas associé à des écarts par rapport à la TAMopt. Néanmoins, la majorité (69 %) des cibles de tension artérielle dépassaient celle de 65 mm Hg préconisée par les lignes directrices Surviving Sepsis. CONCLUSION: Nous avons observé que les cibles de TAMopt étaient très variables chez les patient·es, mais nous n'avons pas observé d'association avec l'incidence de delirium. Des études conçues pour évaluer l'impact sur les issues neurologiques sont nécessaires pour comprendre l'association avec les cibles de tension artérielle moyenne individualisées à l'USI. ENREGISTREMENT DE L'éTUDE: ClinicalTrials.gov (NCT02344043); soumis pour la première fois le 22 janvier 2015.

Short communication: Baroreflex function in embryonic emus (Dromiceius novaehollandiae).

The baroreflex involves cardiovascular homeostatic mechanisms that buffer the system against acute deviations in arterial blood pressure. It is comprised of the cardiac limb which involves adjustments in heart rate and the peripheral limb which involves adjustments in vascular resistance. This negative feedback loop mechanism has been investigated in numerous species of adult vertebrates, however our understanding of the maturation and functional importance of the reflex in developing animals remains poorly understood. In egglaying species, our knowledge of this mechanism is limited to the domestic chicken embryo and the embryonic alligator. While each of these species possess a cardiac baroreflex prior to hatching, they differ in the timing when it becomes functional, with the embryonic chicken possessing the reflex at 90% of incubation, while the alligator possesses the reflex at 70% of incubation. In an effort to determine if bird species might share similar patterns of active baroreflex function, we studied embryonic emus (Dromiceius novaehollandiae). However, we hypothesized that emus would possess a pattern of baroreflex function similar to that of the American alligator given the emu embryo possesses functional vagal tone at 70% of incubation, possibly indicating a more mature collection of cardiovascular control mechanism than those found in embryonic chickens. Our findings illustrate that emu embryos possess a hypotensive baroreflex at 90% of incubation. Therefore, our data fail to support our original hypothesis. While only two species of birds have been studied in this context, it could indicate that baroreflex function is not essential for cardiovascular homeostasis in birds for the majority of in ovo development.

Arterial hypotension "magnitude" and neurological outcome during mechanical thrombectomy under general anesthesia.

INTRODUCTION: Mechanical thrombectomy (MT) is the standard of care for the treatment of acute ischemic stroke (AIS) with large vessel occlusion (LVO), but unfavorable outcomes remain common. Procedural arterial hypotension is associated with poor patient outcome. This study aimed to assess the impact of arterial hypotension "magnitude" (a combination of the depth, defined as the percentage relative to baseline arterial blood pressure, and the duration of hypotensive episodes)" during MT on neurological outcome. METHODS: This is a monocentric retrospective study. Charts were reviewed between January 2018 and June 2021. "Patients were eligible if they were 18 years or older, anterior LVO was diagnosed on cerebral imaging" and MT performed under general anesthesia. Mean arterial pressure (MAP) was recorded every 5 minutes throughout the procedure, and the arterial hypotension "magnitude" was estimated by the area under the curve (AUC) for different thresholds of MAP drops. MAIN OUTCOME MEASURE: The modified Rankin Scale (mRS) at 90 days. MAIN RESULTS: Among the 117 patients analyzed, 46% had poor neurological outcome. Our study showed correlations between poor outcome and a greater procedural AUC of arterial hypotension for the different thresholds: 5% (k 0.18; 95% CI 0.06-0.30; P = 0.007), 10% (k 0.18; 95% CI 0.05-0.30; P = 0.008), 15% (k 0.18; 95% CI 0.04-0.30; P = 0.011), 20% (k 0.18; 95% CI 0.05-0.30; P = 0.010) and 30% (k 0.19; 95% CI 0.05-0.31; P = 0.010). This association persisted after controlling for age, baseline NIHSS score, and ASPECT score. CONCLUSION: The magnitude of hypotension during MT under general anesthesia for AIS is an independent factor of poor outcome at 90 days. These associations have been observed in patients with mild and severe hypotensive episodes.

Evaluation of the agreement between lingual and thoracic limb noninvasive blood pressure with invasive blood pressure measurements in anaesthetized horses.

OBJECTIVE: To evaluate the agreement between noninvasive arterial blood pressure (NIBP) measured from the tongue and thoracic limb with invasive blood pressure (IBP), and to compare NIBP measured from the tongue and thoracic limb in anaesthetized horses. STUDY DESIGN: Prospective clinical study. ANIMALS: A group of eight client-owned healthy horses anaesthetized for scheduled procedures, American Society of Anesthesiologists classification I-II, weighing (mean ± standard deviation) 498 ± 91 kg and aged 7.8 ± 6.75 years. METHODS: Animals were premedicated with intravenous (IV) romifidine (0.04-0.08 mg kg-1) and methadone (0.1 mg kg-1). General anaesthesia was induced IV with ketamine (2.5 mg kg-1) and midazolam (0.05 mg kg-1) and maintained with isoflurane. The facial artery was catheterized for IBP measurements. Systolic (SAP), mean (MAP) and diastolic (DAP) arterial pressures were recorded from the NIBPtongue, NIBPlimb and IBP every 20 minutes during the procedure. Agreement between NIBP and IBP was evaluated based on the American College of Veterinary Internal Medicine criteria and American Association for Medical Instrumentation criteria using the Bland-Altman method. RESULTS: The mean bias and precision between IBP and NIBP measured from the tongue met the standards for all pressure ranges (< 10 mmHg and < 15 mmHg, respectively). NIBP measurements from the tongue and thoracic limb tended to underestimate IBP measurements. During hypotension, MAPtongue and DAPtongue overestimated IBP, but both precision and accuracy met the criteria. The overall accuracy and precision of NIBPlimb was poorer than NIBPtongue. The percentage of NIBPtongue that differed from IBP by < 10 mmHg was higher than that recorded with NIBPlimb for SAP (46% versus 25%), MAP (77% versus 28%) and DAP (79% versus 19%). CONCLUSIONS AND CLINICAL RELEVANCE: The tongue is a clinically suitable alternative for assessing arterial blood pressure compared with the thoracic limb and can reliably detect hypotension in healthy anaesthetized horses.

Browning of perivascular adipose tissue prevents vascular dysfunction and reduces hypertension in angiotensin II-infused mice.

Hypertension is a world-leading cause of cardiovascular disease and premature deaths. Vascular tone is in part regulated by perivascular adipose tissue (PVAT) that releases pro and anticontractile factors. In hypertension, dysfunctional PVAT is observed and studies have indicated a causal relationship between dysfunctional PVAT and vascular damage in hypertension. The phenotype of PVAT on resistance vessels is primarily white adipose tissue. The present study investigates the impact of a changed phenotype, i.e., browning of PVAT, on vascular function and the development of hypertension. Browning was induced by ß3-adrenergic agonist in control and angiotensin II-induced hypertensive mice. Studied parameters included blood pressure by tail-cuff plethysmography and vascular function by wire myography. Browning was confirmed through an immunohistochemical and gene analysis approach. The anticontractile effect of PVAT is lost in untreated hypertensive mice and vascular tone and blood pressure are increased. Browning of PVAT resulted in a maintained anticontractile effect, improved endothelial function, and reduced development of hypertension. Phenotype of PVAT is a major determinant of PVAT health during hypertensive conditions. Our data clearly demonstrates that browning of PVAT, i.e. changing the phenotype of PVAT, protects the vascular function and counteract the development of hypertension. This study provides novel insights into how PVAT can be protected in pathologies and thus limit the development of hypertension.

Connexin 40-Mediated Regulation of Systemic Circulation and Arterial Blood Pressure.

Vascular system is a complex network in which different cell types and vascular segments must work in concert to regulate blood flow distribution and arterial blood pressure. Although paracrine/autocrine signaling is involved in the regulation of vasomotor tone, direct intercellular communication via gap junctions plays a central role in the control and coordination of vascular function in the microvascular network. Gap junctions are made up by connexin (Cx) proteins, and among the four Cxs expressed in the cardiovascular system (Cx37, Cx40, Cx43, and Cx45), Cx40 has emerged as a critical signaling pathway in the vessel wall. This Cx is predominantly found in the endothelium, but it is involved in the development of the cardiovascular system and in the coordination of endothelial and smooth muscle cell function along the length of the vessels. In addition, Cx40 participates in the control of vasomotor tone through the transmission of electrical signals from the endothelium to the underlying smooth muscle and in the regulation of arterial blood pressure by renin-angiotensin system in afferent arterioles. In this review, we discuss the participation of Cx40-formed channels in the development of cardiovascular system, control and coordination of vascular function, and regulation of arterial blood pressure.

The effect of inspiratory muscle training and detraining on the respiratory metaboreflex.

NEW FINDINGS: What is the central question of this study? Is the attenuation of the respiratory muscle metaboreflex preserved after detraining? What is the main finding and its importance? Inspiratory muscle training increased respiratory muscle strength and attenuated the respiratory muscle metaboreflex as evident by lower heart rate and blood pressure. After 5 weeks of no inspiratory muscle training (detraining), respiratory muscle strength was still elevated and the metaboreflex was still attenuated. The benefits of inspiratory muscle training persist after cessation of training, and attenuation of the respiratory metaboreflex follows changes in respiratory muscle strength. ABSTRACT: Respiratory muscle training (RMT) improves respiratory muscle (RM) strength and attenuates the RM metaboreflex. However, the time course of muscle function loss after the absence of training or 'detraining' is less known and some evidence suggest the respiratory muscles atrophy faster than other muscles. We sought to determine the RM metaboreflex in response to 5 weeks of RMT and 5 weeks of detraining. An experimental group (2F, 6M; 26 ± 4years) completed 5 weeks of RMT and tibialis anterior (TA) training (each 5 days/week at 50% of maximal inspiratory pressure (MIP) and 50% maximal isometric force, respectively) followed by 5 weeks of no training (detraining) while a control group (1F, 7M; 24 ± 1years) underwent no intervention. Prior to training (PRE), post-training (POST) and post-detraining (DETR), all participants underwent a loaded breathing task (LBT) to failure (60% MIP) while heart rate and mean arterial blood pressure (MAP) were measured. Five weeks of training increased RM (18 ± 9%, P < 0.001) and TA (+34 ± 19%, P < 0.001) strength and both remained elevated after 5 weeks of detraining (MIP-POST vs. MIP-DETR: 154 ± 31 vs. 153 ± 28 cmH2O, respectively, P = 0.853; TA-POST vs. TA-DETR: 86 ± 19 vs. 85 ± 16 N, respectively, P = 0.982). However, the rise in MAP during LBT was attenuated POST (-11 ± 17%, P = 0.003) and DETR (-9 ± 9%, P = 0.007) during the iso-time LBT. The control group had no change in MIP (P = 0.33), TA strength (P = 0.385), or iso-time MAP (P = 0.867) during LBT across all time points. In conclusion, RM and TA have similar temporal strength gains and the attenuation of the respiratory muscle metaboreflex remains after 5 weeks of detraining.

Predicting intraoperative hypotension: from hope to hype and back to reality.

The analysis of arterial pressure waveforms with machine learning algorithms has been proposed to predict intraoperative hypotension. The ability to forecast arterial hypotension 5-15 min ahead of the fall in blood pressure allows clinicians to be pro-active instead of reactive, and could potentially decrease postoperative morbidity. However, the predictive value of machine learning algorithms has been overestimated due to selection bias in several clinical studies, and they might not be superior to mere observation of arterial pressure. Continuous blood pressure monitoring enables immediate detection of hypotension, and giving fluid, vasopressors or inotropes to patients who are not yet (and might never become) hypotensive based on an algorithm is questionable. Finally, recent prospective interventional studies suggest that reducing intraoperative hypotension does not improve postoperative outcomes.

Intraoperative hypotension and postoperative outcomes: a meta-analysis of randomised trials.

INTRODUCTION: Intraoperative hypotension is associated with adverse postoperative outcomes; however these findings are supported only by observational studies. The aim of this meta-analysis of randomised trials was to compare the postoperative effects permissive management with targeted management of intraoperative blood pressure. METHODS: We searched PubMed, Cochrane, and Embase up to June 2023 for studies comparing permissive (mean arterial pressure ≤60 mm Hg) with targeted (mean arterial pressure >60 mm Hg) intraoperative blood pressure management. Primary outcome was all-cause mortality at the longest follow-up available. Secondary outcomes were atrial fibrillation, myocardial infarction, acute kidney injury, delirium, stroke, number of patients requiring transfusion, time on mechanical ventilation, and length of hospital stay. RESULTS: We included 10 randomised trials including a total of 9359 patients. Mortality was similar between permissive and targeted blood pressure management groups (89/4644 [1.9%] vs 99/4643 [2.1%], odds ratio 0.88, 95% confidence interval [CI], 0.65-1.18, P=0.38, I2=0% with nine studies included). Atrial fibrillation (102/3896 [2.6%] vs 130/3887 [3.3%] odds ratio 0.71, 95% CI 0.53-0.96, P=0.03, I2=0%), and length of hospital stay (mean difference -0.20 days, 95% CI -0.26 to -0.13, P<0.001, I2=0%) were reduced in the permissive management group. No significant differences were found in subgroup analysis for cardiac and noncardiac surgery. CONCLUSION: Pooled randomised evidence shows that a target intraoperative mean arterial pressure ≤60 mm Hg is not associated with increased mortality; nevertheless it is surprisingly associated with a reduced rate of atrial fibrillation and of length of hospital stay. SYSTEMATIC REVIEW PROTOCOL: PROSPERO CRD42023393725.

Quantification of dynamic cerebral autoregulation: welcome to the jungle!

PURPOSE: Patients with dysautonomia often experience symptoms such as dizziness, syncope, blurred vision and brain fog. Dynamic cerebral autoregulation, or the ability of the cerebrovasculature to react to transient changes in arterial blood pressure, could be associated with these symptoms. METHODS: In this narrative review, we go beyond the classical view of cerebral autoregulation to discuss dynamic cerebral autoregulation, focusing on recent advances pitfalls and future directions. RESULTS: Following some historical background, this narrative review provides a brief overview of the concept of cerebral autoregulation, with a focus on the quantification of dynamic cerebral autoregulation. We then discuss the main protocols and analytical approaches to assess dynamic cerebral autoregulation, including recent advances and important issues which need to be tackled. CONCLUSION: The researcher or clinician new to this field needs an adequate comprehension of the toolbox they have to adequately assess, and interpret, the complex relationship between arterial blood pressure and cerebral blood flow in healthy individuals and clinical populations, including patients with autonomic disorders.

An abrupt decrease in arterial blood pressure may predict a high level carbon dioxide embolism in retroperitoneoscopic surgery: case report and a literature review.

BACKGROUND: Carbon dioxide (CO2) embolism is the primary suspect in most cases of intraoperative "cardiovascular" collapse. However, there are few reports about CO2 embolism in retroperitoneal laparoscopy. CASE PRESENTATION: An abrupt decrease in arterial blood pressure was noted in time of retroperitoneoscopic adrenalectomy in a 40 years old male patient with adrenal adenoma. The end-tidal carbon dioxide (EtCO2) and saturation of oxygen were stable with normal cardiography until anesthesiologists found the change of resistant of peripheral circulation, then they gave us a hint of hemorrhage. However, the blood pressure had no reaction to one bolus of epinephrine administration when trying to improve the circulation. Five minutes later, a sudden fall of blood pressure was noted, and then we stopped the processing of cutting tissue and trying to coagulate any bleeding in the operation field. Further vasopressor support proved to be completely ineffective. With the help of transesophageal echocardiography, we found the bubbles in the right atrium, which confirmed the diagnosis of an intraoperative gas embolism (Grade IV). We stopped the carbon dioxide insufflation and deflated the retroperitoneal cavity. All the bubbles in the right atrium totally disappeared and the blood pressure, resistance of peripheral circulation and cardiac output returned to normal 20 min later. We continued the operation and completed it in 40 min with the 10 mmHg air pressure. CONCLUSION: CO2 embolism may occour during retroperitoneoscopic adrenalectomy, and an acute decrease in arterial blood pressure should alert both the urologists and anesthesiologists to this rare and fatal complication.

Diagnostic test accuracy for cessation of circulation during death determination: a systematic review.

PURPOSE: To synthesize the available evidence comparing noninvasive methods of measuring the cessation of circulation in patients who are potential organ donors undergoing death determination by circulatory criteria (DCC) with the current accepted standard of invasive arterial blood pressure (IAP) monitoring. SOURCE: We searched (from inception until 27 April 2021) MEDLINE, Embase, Web of Science, and the Cochrane Central Register of Controlled Trials. We screened citations and manuscripts independently and in duplicate for eligible studies that compared noninvasive methodologies assessing circulation in patients who were monitored around a period of cessation of circulation. We performed risk of bias assessment, data abstraction, and quality assessment using Grading of Recommendations, Assessment, Development, and Evaluation in duplicate and independently. We presented findings narratively. PRINCIPAL FINDINGS: We included 21 eligible studies (N = 1,177 patients). Meta-analysis was not possible because of study heterogeneity. We identified low quality evidence from four indirect studies (n = 89) showing pulse palpation is less sensitive and specific than IAP (reported sensitivity range, 0.76-0.90; specificity, 0.41-0.79). Isoelectric electrocardiogram (ECG) had excellent specificity for death (two studies; 0% [0/510]), but likely increases the average time to death determination (moderate quality evidence). We are uncertain whether point-of-care ultrasound (POCUS) pulse check, cerebral near-infrared spectroscopy (NIRS), or POCUS cardiac motion assessment are accurate tests for the determination of circulatory cessation (very low-quality evidence). CONCLUSION: There is insufficient evidence that ECG, POCUS pulse check, cerebral NIRS, or POCUS cardiac motion assessment are superior or equivalent to IAP for DCC in the setting of organ donation. Isoelectric ECG is specific but can increase the time needed to determine death. Point-of-care ultrasound techniques are emerging therapies with promising initial data but are limited by indirectness and imprecision. STUDY REGISTRATION: PROSPERO (CRD42021258936); first submitted 16 June 2021.

RéSUMé: OBJECTIF: Synthétiser les données probantes disponibles comparant les méthodes non invasives de mesure de l'arrêt de la circulation chez les patients qui sont des donneurs d'organes potentiels soumis à une détermination du décès selon des critères circulatoires (DCC) avec la norme actuellement acceptée de surveillance invasive de la tension artérielle (TA). SOURCES: Nous avons mené des recherches dans les bases de données MEDLINE, EMBASE, Web of Science et le registre Cochrane des essais contrôlés de leur création jusqu'au 27 avril 2021. Nous avons examiné les citations et les manuscrits de manière indépendante et en double pour en tirer les études éligibles qui comparaient des méthodologies non invasives d'évaluation de la circulation chez les patients qui étaient sous surveillance avant, pendant et après une période d'arrêt de la circulation. Nous avons réalisé l'évaluation du risque de biais, l'extraction des données et l'évaluation de la qualité en nous fondant sur la méthodologie GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) en double et de manière indépendante. Nous présentons les résultats de façon narrative. CONSTATATIONS PRINCIPALES: Nous avons inclus 21 études éligibles (N = 1177 patients). Une méta-analyse n'a pas été possible en raison de l'hétérogénéité des études. Nous avons identifié des données de faible qualité issues de quatre études indirectes (n = 89) montrant que la palpation du pouls est moins sensible et spécifique que la mesure invasive de la TA (plage de sensibilité rapportée, 0,76-0,90; spécificité, 0,41-0,79). L'électrocardiogramme (ECG) isoélectrique avait une excellente spécificité pour le décès (deux études; 0 % [0/510]), mais augmente probablement le délai moyen avant la détermination du décès (données probantes de qualité modérée). Nous ne savons pas si la vérification du pouls par échographie ciblée (POCUS), la spectroscopie proche infrarouge (SPIR) cérébrale ou l'évaluation ciblée (POCUS) des mouvements cardiaques sont des examens précis pour la détermination de l'arrêt circulatoire (données probantes de très faible qualité). CONCLUSION: Il n'y a pas suffisamment de données probantes pour affirmer que l'ECG, la vérification ciblée du pouls, la SPIR cérébrale ou l'évaluation ciblée des mouvements cardiaques sont supérieurs ou équivalents à la mesure invasive de la TA pour un DCC dans le cadre du don d'organes. L'ECG isoélectrique est spécifique, mais peut augmenter le délai nécessaire avant de déterminer le décès. Les techniques d'échographie ciblée sont des thérapies émergentes avec des données initiales prometteuses, mais elles sont limitées par leur caractère indirect et l'imprécision de l'examen. ENREGISTREMENT DE L'éTUDE: PROSPERO (CRD42021258936); soumis pour la première fois le 16 juin 2021.

Do higher alarm thresholds for arterial blood pressure lead to less perioperative hypotension? A retrospective, observational cohort study.

Arterial blood pressure is one of the vital signs monitored mandatory in anaesthetised patients. Even short episodes of intraoperative hypotension are associated with increased risk for postoperative organ dysfunction such as acute kidney injury and myocardial injury. Since there is little evidence whether higher alarm thresholds in patient monitors can help prevent intraoperative hypotension, we analysed the blood pressure data before (group 1) and after (group 2) the implementation of altered hypotension alarm settings. The study was conducted as a retrospective observational cohort study in a large surgical centre with 32 operating theatres. Alarm thresholds for hypotension alarm for mean arterial pressure (MAP) were altered from 60 (before) to 65 mmHg for invasive measurement and 70 mmHg for noninvasive measurement. Blood pressure data from electronic anaesthesia records of 4222 patients (1982 and 2240 in group 1 and 2, respectively) with 406,623 blood pressure values undergoing noncardiac surgery were included. We analysed (A) the proportion of blood pressure measurements below the threshold among all measurements by quasi-binomial regression and (B) whether at least one blood pressure measurement below the threshold occurred by logistic regression. Hypotension was defined as MAP < 65 mmHg. There was no significant difference in overall proportions of hypotensive episodes for mean arterial pressure before and after the adjustment of alarm settings (mean proportion of values below 65 mmHg were 6.05% in group 1 and 5.99% in group 2). The risk of ever experiencing a hypotensive episode during anaesthesia was significantly lower in group 2 with an odds ratio of 0.84 (p = 0.029). In conclusion, higher alarm thresholds do not generally lead to less hypotensive episodes perioperatively. There was a slight but significant reduction of the occurrence of intraoperative hypotension in the presence of higher thresholds for blood pressure alarms. However, this reduction only seems to be present in patients with very few hypotensive episodes.

Arterial blood pressure waveform in liver transplant surgery possesses variability of morphology reflecting recipients' acuity and predicting short term outcomes.

We investigated clinical information underneath the beat-to-beat fluctuation of the arterial blood pressure (ABP) waveform morphology. We proposed the Dynamical Diffusion Map algorithm (DDMap) to quantify the variability of morphology.  The underlying physiology could be the compensatory mechanisms involving complex interactions between various physiological mechanisms to regulate the cardiovascular system. As a liver transplant surgery contains distinct periods, we investigated its clinical behavior in different surgical steps. Our study used DDmap algorithm, based on unsupervised manifold learning, to obtain a quantitative index for the beat-to-beat variability of morphology. We examined the correlation between the variability of ABP morphology and disease acuity as indicated by Model for End-Stage Liver Disease (MELD) scores, the postoperative laboratory data, and 4 early allograft failure (EAF) scores. Among the 85 enrolled patients, the variability of morphology obtained during the presurgical phase was best correlated with MELD-Na scores. The neohepatic phase variability of morphology was associated with EAF scores as well as postoperative bilirubin levels, international normalized ratio, aspartate aminotransferase levels, and platelet count. Furthermore, variability of morphology presents more associations with the above clinical conditions than the common BP measures and their BP variability indices. The variability of morphology obtained during the presurgical phase is indicative of patient acuity, whereas those during the neohepatic phase are indicative of short-term surgical outcomes.

Are NIRS-derived cerebral autoregulation and ABPopt values different between hemispheres in hypoxic-ischemic brain injury patients following cardiac arrest?

PURPOSE: Near-infrared spectroscopy (NIRS) has been suggested as a non-invasive monitoring technique to set cerebral autoregulation (CA) guided ABP targets (ABPopt) in comatose patients with hypoxic-ischemic brain injury (HIBI) following cardiac arrest. We aimed to determine whether NIRS-derived CA and ABPopt values differ between left and right-sided recordings in these patients. METHODS: Bifrontal regional oxygen saturation (rSO2) was measured using INVOS or Fore-Sight devices. The Cerebral Oximetry index (COx) was determined as a CA measure. ABPopt was calculated using a published algorithm with multi-window weighted approach. A paired Wilcoxon signed rank test and intraclass correlation coefficients (ICC) were used to compare (1) systematic differences and (2) degree of agreement between left and right-sided measurements. RESULTS: Eleven patients were monitored. In one patient there was malfunctioning of the right-sided optode and in one patient not any ABPopt value was calculated. Comparison of rSO2 and COx was possible in ten patients and ABPopt in nine patients. The average recording time was 26 (IQR, 22-42) hours. The ABPopt values were not significantly different between the bifrontal recordings (80 (95%-CI 76-84) and 82 (95%-CI 75-84) mmHg) for the left and right recordings, p = 1.0). The ICC for ABPopt was high (0.95, 0.78-0.98, p < 0.001). Similar results were obtained for rSO2 and COx. CONCLUSION: We found no differences between left and right-sided NIRS recordings or CA estimation in comatose and ventilated HIBI patients. This suggests that in these patients without signs of localized pathology unilateral recordings might be sufficient to estimate CA status or provide ABPopt targets.

Higher blood pressure versus normotension targets to prevent acute kidney injury: a systematic review and meta-regression of randomized controlled trials.

BACKGROUND: Renal hypoperfusion is one of the most common causes of acute kidney injury (AKI), especially in shock and perioperative patients. An optimal blood pressure (BP) target to prevent AKI remains undetermined. We conducted a systematic review and meta-analysis of available randomized clinical trial (RCT) results to address this knowledge gap. METHODS: From inception to May 13, 2022, we searched Ovid Medline, EMBASE, Cochrane Library, SCOPUS, clinicaltrials.gov, and WHO ICTRP for RCTs comparing higher BP target versus normotension in hemodynamically unstable patients (shock, post-cardiac arrest, or surgery patients). The outcomes of interest were post-intervention AKI rate and renal replacement therapy (RRT) rate. Two investigators independently screened the citations and reviewed the full texts for eligible studies according to a predefined form. RESULTS: Twelve trials were included, enrolling a total of 5759 participants, with shock, non-cardiac, and cardiac surgery patients accounting for 3282 (57.0%), 1687 (29.3%) and 790 (13.7%) patients, respectively. Compared to lower mean arterial blood pressure (MAP) targets that served as normotension, targeting higher MAP had no significant effect on AKI rates in shock (RR [95% CI] = 1.10 [0.93, 1.29]), in cardiac-surgery (RR [95% CI] = 0.87 [0.73, 1.03]) and non-cardiac surgery patients (RR [95% CI] = 1.25 [0.98, 1.60]) using random-effects meta-analyses. In shock patients with premorbid hypertension, however, targeting MAP above 70 mmHg resulted in significantly lower RRT risks, RR [95%CI] = 1.20 [1.03, 1.41], p < 0.05. CONCLUSIONS: Targeting a higher MAP in shock or perioperative patients may not be superior to normotension, except in shock patients with premorbid hypertension. Further studies are needed to assess the effects of a high MAP target to preventing AKI in hypertensive patients across common settings of hemodynamic instability. Trial registration This systematic review has been registered on PROSPERO ( CRD42021286203 ) on November 19, 2021, prior to data extraction and analysis.