Intraoperative hypotension and its prediction

Intraoperative hypotension (IOH) very commonly accompanies general anaesthesia in patients undergoing major surgical procedures. The development of IOH is unwanted, since it is associated with adverse outcomes such as acute kidney injury and myocardial injury, stroke and mortality. Although the definition of IOH is variable, harm starts to occur below a mean arterial pressure (MAP) threshold of 65 mmHg. The odds of adverse outcome increase for increasing duration and/or magnitude of IOH below this threshold, and even short periods of IOH seem to be associated with adverse outcomes. Therefore, reducing the hypotensive burden by predicting and preventing IOH through proactive appropriate treatment may potentially improve patient outcome. In this review article, we summarise the current state of the prediction of IOH by the use of so-called machine-learning algorithms. Machine-learning algorithms that use high-fidelity data from the arterial pressure waveform, may be used to reveal 'traits' that are unseen by the human eye and are associated with the later development of IOH. These algorithms can use large datasets for 'training', and can subsequently be used by clinicians for haemodynamic monitoring and guiding therapy. A first clinically available application, the hypotension prediction index (HPI), is aimed to predict an impending hypotensive event, and additionally, to guide appropriate treatment by calculated secondary variables to asses preload (dynamic preload variables), contractility (dP/dt(max)), and afterload (dynamic arterial elastance, Ea(dyn)). In this narrative review, we summarise the current state of the prediction of hypotension using such novel, automated algorithms and we will highlight HPI and the secondary variables provided to identify the probable origin of the (impending) hypotensive event

Journal of Clinical Monitoring and Computing 2019 end of year summary:monitoring tissue oxygenation and perfusion and its autoregulation

Tissue perfusion monitoring is increasingly being employed clinically in a non-invasive fashion. In this end-of-year summary of the Journal of Clinical Monitoring and Computing, we take a closer look at the papers published recently on this subject in the journal. Most of these papers focus on monitoring cerebral perfusion (and associated hemodynamics), using either transcranial doppler measurements or near-infrared spectroscopy. Given the importance of cerebral autoregulation in the analyses performed in most of the studies discussed here, this end-of-year summary also includes a short description of cerebral hemodynamic physiology and its autoregulation. Finally, we review articles on somatic tissue oxygenation and its possible association with outcome

Crossover from Anderson- to Kondo-like behavior: Universality induced by spin-charge separation

The thermodynamics of a lattice regularized asymmetric Anderson impurity in a correlated host is obtained by an exact solution. The crossover from the Anderson- to the Kondo-regime is studied, thus making contact with predictions by scaling theory. On the basis of the exact solution, the transition to universal Kondo behavior is shown to be realized by a graduate separation of the energy scales of spin and charge excitations.Comment: 18 pages, 5 figure

Microvascular effects of oxygen and carbon dioxide measured by vascular occlusion test in healthy volunteers

BACKGROUND: Changes in near-infrared spectroscopy-derived regional tissue oxygen saturation (StO2) during a vascular occlusion test (VOT; ischemic provocation of microcirculation by rapid inflation and deflation of a tourniquet) allow estimating peripheral tissue O2 consumption (desaturation slope; DS), vascular reactivity (recovery slope; RS) and post-ischemic hyperperfusion (AUC-H). The effects of isolated alterations in the inspiratory fraction of O2 (FiO2) and changes in expiratory CO2 remain to be elucidated. Therefore, in this secondary analysis we determined the effects of standardized isolated instances of hypoxia, hyperoxia, hypocapnia and hypercapnia on the VOT-induced StO2 changes in healthy volunteers (n = 20) to establish reference values for future physiological studies. METHODS: StO2 was measured on the thenar muscle. Multiple VOTs were performed in a standardized manner: i.e. at room air (baseline), during hyperoxia (FiO2 1.0), mild hypoxia (FiO2 ≈ 0.11), and after a second baseline, during hypocapnia (end-tidal CO2 (etCO2) 2.5-3.0 vol%) and hypercapnia (etCO2 7.0-7.5 vol%) at room air. Differences in DS, RS, and AUC-H were tested using repeated-measures ANOVA. RESULTS: DS and RS remained constant during all applied conditions. AUC-H after hypoxia was smaller compared to hyperoxia (963 %*sec vs hyperoxia 1702 %*sec, P = 0.005), while there was no difference in AUC-H duration between hypoxia and baseline. The StO2 peak (after tourniquet deflation) during hypoxia was lower compared to baseline and hyperoxia (92 % vs 94 % and 98 %, P < 0.001). CONCLUSION: We conclude that in healthy volunteers at rest, common situations observed during anesthesia and intensive care such as exposure to hypoxia, hyperoxia, hypocapnia, or hypercapnia, did not affect peripheral tissue O2 consumption and vascular reactivity as assessed by VOT-induced changes in StO2. These observations may serve as reference values for future physiological studies. TRIAL REGISTRATION: This study represents a secondary analysis of an original study which has been registered at ClinicalTrials.gov nr: NCT02561052

Do alterations in pulmonary vascular tone result in changes in central blood volumes? An experimental study:An experimental study

BACKGROUND: The effects of selective pulmonary vascular tone alterations on cardiac preload have not been previously examined. Therefore, we evaluated whether changing pulmonary vascular tone either by hypoxia or the inhalation of aerosolized prostacyclin (PGI(2)) altered intrathoracic or pulmonary blood volume (ITBV, PBV, respectively), both as surrogate for left ventricular preload. Additionally, the mean systemic filling pressure analogue (Pmsa) and pressure for venous return (Pvr) were calculated as surrogate of right ventricular preload. METHODS: In a randomized controlled animal study in 6 spontaneously breathing dogs, pulmonary vascular tone was increased by controlled moderate hypoxia (FiO(2) about 0.10) and decreased by aerosolized PGI(2). Also, inhalation of PGI(2) was instituted to induce pulmonary vasodilation during normoxia and hypoxia. PBV, ITBV and circulating blood volume (Vd(circ)) were measured using transpulmonary thermo-dye dilution. Pmsa and Pvr were calculated post hoc. Either the Wilcoxon-signed rank test or Friedman ANOVA test was performed. RESULTS: During hypoxia, mean pulmonary artery pressure (PAP) increased from median [IQR] 12 [8–15] to 19 [17–25] mmHg (p < 0.05). ITBV, PBV and their ratio with Vd(circ) remained unaltered, which was also true for Pmsa, Pvr and cardiac output. PGI(2) co-inhalation during hypoxia normalized mean PAP to 13 (12–16) mmHg (p < 0.05), but left cardiac preload surrogates unaltered. PGI(2) inhalation during normoxia further decreased mean PAP to 10 (9–13) mmHg (p < 0.05) without changing any of the other investigated hemodynamic variables. CONCLUSIONS: In spontaneously breathing dogs, changes in pulmonary vascular tone altered PAP but had no effect on cardiac output, central blood volumes or their relation to circulating blood volume, nor on Pmsa and Pvr. These observations suggest that cardiac preload is preserved despite substantial alterations in right ventricular afterload

The effect of compliance with a perioperative goal-directed therapy protocol on outcomes after high-risk surgery:a before-after study

Perioperative goal-directed therapy is considered to improve patient outcomes after high-risk surgery. The association of compliance with perioperative goal-directed therapy protocols and postoperative outcomes is unclear. The purpose of this study is to determine the effect of protocol compliance on postoperative outcomes following high-risk surgery, after implementation of a perioperative goal-directed therapy protocol. Through a before-after study design, patients undergoing elective high-risk surgery before (before-group) and after implementation of a perioperative goal-directed therapy protocol (after-group) were included. Perioperative goal-directed therapy in the after-group consisted of optimized stroke volume variation or stroke volume index and optimized cardiac index. Additionally, the association of protocol compliance with postoperative complications when using perioperative goal-directed therapy was assessed. High protocol compliance was defined as >= 85% of the procedure time spent within the individual targets. The difference in complications during the first 30 postoperative days before and after implementation of the protocol was assessed. In the before-group, 214 patients were included and 193 patients in the after-group. The number of complications was higher in the before-group compared to the after-group (n = 414 vs. 282; p = 0.031). In the after-group, patients with high protocol compliance for stroke volume variation or stroke volume index had less complications compared to patients with low protocol compliance for stroke volume variation or stroke volume index (n = 187 vs. 90; p = 0.01). Protocol compliance by the attending clinicians is essential and should be monitored to facilitate an improvement in postoperative outcomes desired by the implementation of perioperative goal-directed therapy protocols

A novel doxorubicin-glucuronide prodrug DOX-GA3 for tumour-selective chemotherapy: distribution and efficacy in experimental human ovarian cancer

The doxorubicin (DOX) prodrug N -[4-doxorubicin- N -carbonyl (oxymethyl) phenyl] O -β-glucuronyl carbamate (DOX-GA3) was synthesised for specific activation by human β-glucuronidase, which is released in necrotic areas of tumour lesions. This novel prodrug was completely activated to the parent drug by human β-glucuronidase with V max= 25.0 μmol min–1mg–1and K m= 1100 μM. The pharmacokinetics and distribution of DOX-GA3 in nude mice bearing human ovarian cancer xenografts (OVCAR-3) were determined and compared with DOX. Administration of DOX at 8 mg kg–1i.v. (maximum tolerated dose, MTD) to OVCAR-3-bearing mice resulted in a peak plasma concentration of the drug of 16.4 μM (t = 1 min). A 7.6-times lower peak plasma concentration of DOX was measured after injection of DOX-GA3 at 250 mg kg–1i.v. (50% of MTD). In normal tissues the prodrug showed peak DOX concentrations that were up to 5-fold (heart) lower than those found after DOX administration. DOX-GA3 activation by β-glucuronidase in the tumour yielded an almost 5-fold higher DOX peak concentration of 9.57 nmol g–1(P< 0.05) than the peak concentration of only 2.14 nmol g–1observed after DOX. As a consequence, the area under the curve of DOX calculated in tumour tissue after DOX-GA3 (13.1 μmol min–1g–1) was 10-fold higher than after DOX (1.31 μmol min–1g–1). The anti-tumour effects of DOX-GA3 and DOX were compared at equitoxic doses in OVCAR-3 xenografts at a mean tumour size of 125 mm3. The prodrug given i.v. at 500 mg kg–1weekly × 2 resulted in a maximum tumour growth inhibition of 87%, while the standard treatment with DOX at a dose of 8 mg kg–1i.v. weekly × 2 resulted in a maximum tumour growth inhibition of only 56%. Treatment with DOX-GA3 was also given to mice with larger tumours containing more necrosis. For tumours with a mean size of 400 mm3the specific growth delay by DOX-GA3 increased from 2.7 to 3.9. Our data indicate that DOX-GA3 is more effective than DOX and suggest that the prodrug will be specifically advantageous for treatment of advanced disease. © 2001 Cancer Research Campaign http://www.bjcancer.co