Improving the acute and perioperative hemodynamic assessment

First, this thesis aimed to extend the evidence on the applicability of hemodynamic monitoring during the perioperative period and after admission to the ICU. Second, we aimed to gain knowledge on how to improve the conduct of studies in perioperative and critical care medicine.We provided an overview of the current evidence for hemodynamic monitoring in perioperative goal-directed therapy. We showed that the studies on this subject showed clinical heterogeneity and risk of bias. Extension of all aspects of hemodynamic monitoring was considered in this thesis. A study was performed on the educated guess of physicians when estimating cardiac output using clinical examination to help improve the reliability of the clinical examination. We showed that physicians at the bed-side mainly consider mottling score and norepinephrine dose when estimating cardiac output. In another study, we demonstrated that blood pressure measurements differ when measured invasively or non-invasively and that these differences may have clinical consequences. We also showed that echocardiography could be performed by novices, but experts are needed to interpret obtained images. We demonstrated that cardiac output measurements vary in critically ill patients when measured with echocardiography or uncalibrated pulse wave analysis.For the second part of this thesis, we demonstrated that various mortality prediction models exist for critically ill patients. Quality of methodology often lacks for these models, and improvements have to be made to help patient care. To help improve the quality of studies, we finally propose that study protocols are prepublished and made available for peer-review before conduct

Cardiovascular features of possible autonomous cortisol secretion in patients with adrenal incidentalomas

Background: Low-grade incomplete post-dexamethasone cortisol suppression in patients with adrenal incidentalomas – recently defined as possible autonomous cortisol secretion (pACS) – has been associated with increased cardiovascular events and mortality. However, prospective studies documenting cardiac abnormalities in these patients are lacking. Subjects and methods: Between July 2016 and September 2017, 71 consecutive patients with adrenal lesions were prospectively screened for hypercortisolism by dexamethasone suppression test (NCT 02611258). Complete anthropometric, metabolic and hormonal parameters were recorded along with full cardiac ultrasound assessment and noninvasive measurement of arterial stiffness. All patients underwent chemical-shift magnetic resonance imaging to characterize the lesions. Cardiovascular outcomes were recorded in blind. Results: According to post-dexamethasone suppression cortisol values (post-DST), 34 patients had pACS and 37 nonfunctioning adenomas (NFA). The two groups were similar in sex, BMI, age distribution, cardiovascular risk factors and comorbidities. Left ventricular mass index (LVMIBSA) was increased in pACS compared to NFA (P=0.006) and mildly correlated to the post-DST cortisol level (rho=0.347; P=0.004). The post-DST cortisol levels explained up to 13.7% of LVMIBSAvariance (P=0.002). Compared to NFA, patients with pACS had a higher prevalence of diastolic dysfunction (35.1% vs 82.6%; P=0.001) and worse arterial stiffness assessed by pulse wave velocity (P=0.033). Conclusions: In apparently asymptomatic patients, mild autonomous cortisol secretion can sustain early cardiac and vascular remodeling, independently of other risk factors. The morphological and functional cardiovascular changes observed in pACS underline the need for further studies to correctly define the long-term management of this relatively common condition

Zbrinjavanje hitnih stanja vezanih uz arterijsku hipertenziju u izvanbolničkoj hitnoj medicinskoj službi

SUMMARY Arterial hypertension is the most common cause of cardiovascular diseases and mortality. It significantly contributes to the incidence of other chronic diseases, the most frequent being myocardial infarction and stroke. Arterial hypertension, whether chronically uncontrolled or especially in case of hypertensive emergency, represents a complex state that must be adequately assessed and managed. Hypertensive emergencies are not common in the general population, but represent a serious health emergency that can rapidly lead to irreversible damage and loss of function of target organs if not treated adequately. Prompt and effective treatment in prehospital emergency care significantly contributes to the overall quality of the healthcare system.SAŽETAK Arterijska je hipertenzija najčešći uzrok kardiovaskularnih bolesti kao i smrtnosti. Znatno pridonosi učestalosti ostalih kroničnih bolesti, od kojih su najučestalije infarkt miokarda i moždani udar. Arterijska hipertenzija, bilo ona kronična neregulirana, a posebno u slučaju hipertenzivne hitnoće ili emergencije, kompleksno je stanje koje je potrebno odgovarajuće procijeniti i zbrinuti. Hipertenzivne emergencije nisu učestale u populaciji, ali su ozbiljna hitna stanja koja u kratkom vremenu, ako se odgovarajuće ne zbrinu, uzrokuju ireverzibilno oštećenje i gubitak funkcije ciljnih organa. Promptno i učinkovito postupanje u izvanbolničkoj hitnoj medicinskoj službi znatno doprinosi kvaliteti cjelokupnoga zdravstvenog sustava

Blood pressure thresholds in pregnancy for identifying maternal and infant risk: A secondary analysis of community-level interventions for pre-eclampsia (CLIP) trial data

Background: Blood pressure measurement is a marker of antenatal care quality. In well resourced settings, lower blood pressure cutoffs for hypertension are associated with adverse pregnancy outcomes. We aimed to study the associations between blood pressure thresholds and adverse outcomes and the diagnostic test properties of these blood pressure cutoffs in low-resource settings.Methods: We did a secondary analysis of data from 22 intervention clusters in the Community-Level Interventions for Pre-eclampsia (CLIP) cluster randomised trials (NCT01911494) in India (n=6), Mozambique (n=6), and Pakistan (n=10). We included pregnant women aged 15-49 years (12-49 years in Mozambique), identified in their community by trained community health workers, who had data on blood pressure measurements and outcomes. The trial was unmasked. Maximum blood pressure was categorised as: normal blood pressure (systolic blood pressure [sBP] [dBP] Hg), elevated blood pressure (sBP 120-129 mm Hg and dBP Hg), stage 1 hypertension (sBP 130-139 mm Hg or dBP 80-89 mm Hg, or both), non-severe stage 2 hypertension (sBP 140-159 mm Hg or dBP 90-109 mm Hg, or both), or severe stage 2 hypertension (sBP ≥160 mm Hg or dBP ≥110 mm Hg, or both). We classified women according to the maximum blood pressure category reached across all visits for the primary analyses. The primary outcome was a maternal, fetal, or neonatal mortality or morbidity composite. We estimated dose-response relationships between blood pressure category and adverse outcomes, as well as diagnostic test properties.Findings: Between Nov 1, 2014, and Feb 28, 2017, 21 069 women (6067 in India, 4163 in Mozambique, and 10 839 in Pakistan) contributed 103 679 blood pressure measurements across the three CLIP trials. Only women with non-severe or severe stage 2 hypertension, as discrete diagnostic categories, experienced more adverse outcomes than women with normal blood pressure (risk ratios 1·29-5·88). Using blood pressure categories as diagnostic thresholds (women with blood pressure within the category or any higher category vs those with blood pressure in any lower category), dose-response relationships were observed between increasing thresholds and adverse outcomes, but likelihood ratios were informative only for severe stage 2 hypertension and maternal CNS events (likelihood ratio 6·36 [95% CI 3·65-11·07]) and perinatal death (5·07 [3·64-7·07]), particularly stillbirth (8·53 [5·63-12·92]).Interpretation: In low-resource settings, neither elevated blood pressure nor stage 1 hypertension were associated with maternal, fetal, or neonatal mortality or morbidity adverse composite outcomes. Only the threshold for severe stage 2 hypertension met diagnostic test performance standards. Current diagnostic thresholds for hypertension in pregnancy should be retained.Funding: University of British Columbia, the Bill & Melinda Gates Foundation

Noninvasive cardiac output and central systolic pressure from cuff-pressure and pulse wave velocity

Goal: We introduce a novel approach to estimate cardiac output (CO) and central systolic blood pressure (cSBP) from noninvasive measurements of peripheral cuff-pressure and carotid-to-femoral pulse wave velocity (cf-PWV). Methods: The adjustment of a previously validated one-dimensional arterial tree model is achieved via an optimization process. In the optimization loop, compliance and resistance of the generic arterial tree model as well as aortic flow are adjusted so that simulated brachial systolic and diastolic pressures and cf-PWV converge towards the measured brachial systolic and diastolic pressures and cf-PWV. The process is repeated until full convergence in terms of both brachial pressures and cf-PWV is reached. To assess the accuracy of the proposed framework, we implemented the algorithm on in vivo anonymized data from 20 subjects and compared the method-derived estimates of CO and cSBP to patient-specific measurements obtained with Mobil-O-Graph apparatus (central pressure) and two-dimensional transthoracic echocardiography (aortic blood flow). Results: Both CO and cSBP estimates were found to be in good agreement with the reference values achieving an RMSE of 0.36 L/min and 2.46 mmHg, respectively. Low biases were reported, namely -0.04 +/- 0.36 L/min for CO predictions and -0.27 +/- 2.51 mmHg for cSBP predictions. Significance: Our one-dimensional model can be successfully "tuned" to partially patient-specific standards by using noninvasive, easily obtained peripheral measurement data. The in vivo evaluation demonstrated that this method can potentially be used to obtain central aortic hemodynamic parameters in a noninvasive and accurate way

Assessment and risk stratification of ageing-related target organ damage and adverse health outcomes in the general population

The objectives of this doctoral thesis are to address the contribution of blood pressure to the presence of subclinical target-organ damage and the development of adverse health complications that associate with a poor life course of aging. This thesis focuses on ambulatory blood pressure monitoring to provide the most accurate information about the blood pressure level and variability over a 24-hour period. Moreover, by investigating the role of novel markers, including imaging markers and biomarkers, this thesis also provides possible pathophysiological and biological mechanisms that might explain the association between vascular risk factors and adverse health complications. We envisage that the results of our study will contribute to the refinement of risk stratification of major micro- (ophthalmological, neurological) and macro‑vascular (neurological, cardiovascular) complications associated with poor aging