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Background: Lactate is a commonly used biomarker for sepsis, although it has limitations in certain cases, suggesting the need for novel biomarkers. We evaluated the diagnostic accuracy of plasma renin concentration and renin activity for mortality and kidney outcomes in patients with sepsis with hypoperfusion or hypotension., Methods: This was a multicenter, prospective, observational study of 117 patients with septic shock treated at three tertiary emergency departments between September 2021 and October 2022. The accuracy of renin activity, renin, and lactate concentrations in predicting 28-day mortality, acute kidney injury (AKI), and renal replacement requirement was assessed using the area under the ROC curve (AUC) analysis., Results: The AUCs of initial renin activity, renin, and lactate concentrations for predicting 28-day mortality were 0.66 (95% confidence interval [CI], 0.55-0.77), 0.63 (95% CI, 0.52-0.75), and 0.65 (95% CI, 0.53-0.77), respectively, and those at 24 hrs were 0.74 (95% CI, 0.62-0.86), 0.70 (95% CI, 0.56-0.83), and 0.67 (95% CI, 0.54-0.79). Renin concentrations and renin activity outperformed initial lactate concentrations in predicting AKI within 14 days. The AUCs of renin and lactate concentrations were 0.71 (95% CI, 0.61-0.80) and 0.57 (95% CI, 0.46-0.67), respectively ( P =0.030). The AUC of renin activity (0.70; 95% CI, 0.60-0.80) was also higher than that of lactate concentration ( P =0.044)., Conclusions: Renin concentration and renin activity show comparable performance to lactate concentration in predicting 28-day mortality in patients with septic shock but superior performance in predicting AKI.

Background: Post-induction hypotension (PIH) often occurs during general anesthesia induction. This study aimed to investigate blood catecholamine levels during induction of general anesthesia in patients with PIH undergoing laparoscopic cholecystectomy., Methods: This prospective study included 557 adult patients who underwent laparoscopic cholecystectomy under general anesthesia. PIH was defined as a greater than 20% decrease in systolic blood pressure from the pre-induction value, a systolic arterial pressure of less than 90 mmHg, or both. Plasma concentrations of epinephrine and norepinephrine during the induction of general anesthesia were determined using enzyme-linked immunosorbent assay. Multivariate logistic regression analysis evaluated the association between the clinical factors and PIH., Results: Of the 557 patients, 390 had PIH, and the remaining 167 were allocated to the non-PIH group. Changes in blood adrenaline, noradrenaline levels, or both were more pronounced in the PIH than in the non-PIH group (p<0.05). Age, body mass index, a history of hypertension, preoperative systolic blood pressure, and propofol or sufentanil dose were independent predictors of PIH., Conclusion: The changes of blood catecholamines in patients with more stable hemodynamics during the induction of general anesthesia are smaller than that in patients with post-induction hypotension., Trial Registration: ChiCTR2200055549, 12/01/2022., Competing Interests: The authors declare that they have no conflict of interest., (Copyright: © 2024 Yao et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Intradialytic hypotension (IDH) is a common complication in maintaining hemodialysis (MHD) patients. Immune activation might be part of the mechanisms. However, the association between pro-inflammatory cytokines and blood pressure (BP) has not been deeply explored. So we aim to evaluate the potential role of pro-inflammatory cytokines in IDH., Methods: MHD patients starting hemodialysis before January 2016 were enrolled in our retrospective study. Patients' characteristics, laboratory results, and intradialytic BP were collected. IDH was defined as nadir systolic BP ≤ 90 mmHg during hemodialysis. The definition of IDH group was that those who suffered from more than one hypotensive event during one month after the enrollment (10% of dialysis treatments). Spearman correlation analysis and logistic regression were employed to explore the relationship between pro-inflammatory cytokines and IDH., Results: Among 390 patients, 72 were identified with IDH (18.5%). High levels of serum tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) were observed in the IDH group ( p  < 0.001). Both TNF-α and IL-1β positively correlated with predialysis BP ( p  < 0.01). Receiver operating characteristic curve (ROC) analysis was used to evaluate the diagnostic accuracy of serum IL-1β and TNF-α for IDH. The area under the curve of IL-1β was 0.772 (95% CI: 0.708-0.836, p  < 0.01), and that of TNF-α was 0.701 (95% CI: 0.620-0.781, p  < 0.01). After adjusting for patients' characteristics, biochemical parameters, comorbid conditions, predialysis BP, and medications, elevated TNF-α and IL-1β were still risk factors for IDH., Conclusion: Pro-inflammatory cytokines (TNF-α and IL-1β) could be potential predictors for IDH.

Puumala hantavirus (PUUV) causes hemorrhagic fever with renal syndrome. We aimed to evaluate whether ABO and rhesus blood groups associate with the susceptibility or the severity of PUUV infection. We analyzed blood groups in 289 adult patients treated in Tampere University hospital due to PUUV infection during the years 1982-2017. Patients' blood group distribution was compared to that of healthy, voluntary blood donors living in the Tampere University Hospital responsibility area ( n = 21,833). The severity of PUUV infection, as judged by the severity of acute kidney injury (AKI), thrombocytopenia, inflammation, capillary leakage, and the length of hospital care, was analyzed across the groups. The ABO and rhesus blood group distributions did not differ between the patients and blood donors. Patients with non-O blood groups had lower systolic blood pressure compared to patients with blood group O, but there was no difference in other markers of capillary leakage or in the severity of AKI. Minor deviations in the number of platelets and leukocytes were detected between the O and non-O blood groups. To conclude, patients with blood group O may be less susceptible to hypotension, but otherwise blood groups have no major influences on disease susceptibility or severity during acute PUUV infection.

Background: Primary graft dysfunction (PGD) is the main cause of death in the first 30 days after heart transplantation (HTX), accounting for approximately 40% of mortality. The study's primary aim was to assess the incidence of PGD, following the International Society for Heart and Lung Transplantation consensus, and to compare it with the incidence of significant postoperative hypotension despite administration of high-dose inotropes and vasoconstrictors. The secondary aim of the study was to determine changes in biochemical markers that accompany the phenomenon., Methods: Forty-five patients who underwent HTX between 2010 and 2015 were enrolled in this study, and detailed hemodynamic and metabolic data from the first 48 postoperative hours were collected and analyzed. Hemodynamic instability was defined as significant postoperative hypotension (mean arterial pressure (MAP) < 60 mmHg) combined with a high inotrope score (> 10). Data for long-term mortality were obtained from the population registration office., Results: PGD incidence was relatively low (17.8%); however, hemodynamic instability was common (40%). Among unstable patients, MAP was insufficient for end-organ perfusion (51.4 ± 9.5 mmHg) but no decrease in left ventricular function was observed (cardiac index, 2.65 ± 0.6 l/min/m2; left ventricular ejection fraction, 52.9 ± 15.5%). Within this group, mean systemic vascular resistance index (961 ± 288 dyn*s*m2/cm5) was low despite receiving high doses of vasoactive agent (norepinephrine 0.21 (0.06-0.27) μg/kg/min during first 24 h postoperatively and 0.21 (0.01-0.27) μg/kg/min during next 24 h postoperatively). After HTX, serum lactate levels were initially significantly higher in patients with hemodynamic instability (p = 0.002); however, impaired lactate clearance was not observed (p = 0.366), and lactate levels normalized within the first 24 h postoperatively. Postoperative hemodynamic instability altered the long-term outcome and increased 5-year mortality after HTX (p = 0.034)., Conclusions: Hemodynamic instability is a more common phenomenon than PGD. Only early postoperative serum lactate levels correspond with hemodynamic instability following HTX. Postoperative hemodynamic instability is associated with poor long-term survival among HTX recipients., (© 2021. The Author(s).)

Background: The impact of the permissive hypotension approach in clinically well infants on regional cerebral oxygen saturation (rScO 2 ) and autoregulatory capacity (CAR) remains unknown., Methods: Prospective cohort study of blinded rScO 2 measurements within a randomized controlled trial of management of hypotension (HIP trial) in extremely preterm infants. rScO 2 , mean arterial blood pressure, duration of cerebral hypoxia, and transfer function (TF) gain inversely proportional to CAR, were compared between hypotensive infants randomized to receive dopamine or placebo and between hypotensive and non-hypotensive infants, and related to early intraventricular hemorrhage or death., Results: In 89 potentially eligible HIP trial patients with rScO 2 measurements, the duration of cerebral hypoxia was significantly higher in 36 hypotensive compared to 53 non-hypotensive infants. In 29/36 hypotensive infants (mean GA 25 weeks, 69% males) receiving the study drug, no significant difference in rScO 2 was observed after dopamine (n = 13) compared to placebo (n = 16). Duration of cerebral hypoxia was associated with early intraventricular hemorrhage or death.  Calculated TF gain (n = 49/89) was significantly higher reflecting decreased CAR in 16 hypotensive compared to 33 non-hypotensive infants., Conclusions: Dopamine had no effect on rScO 2 compared to placebo in hypotensive infants. Hypotension and cerebral hypoxia are associated with early intraventricular hemorrhage or death., Impact: Treatment of hypotension with dopamine in extremely preterm infants increases mean arterial blood pressure, but does not improve cerebral oxygenation. Hypotensive extremely preterm infants have increased duration of cerebral hypoxia and reduced cerebral autoregulatory capacity compared to non-hypotensive infants. Duration of cerebral hypoxia and hypotension are associated with early intraventricular hemorrhage or death in extremely preterm infants. Since systematic treatment of hypotension may not be associated with better outcomes, the diagnosis of cerebral hypoxia in hypotensive extremely preterm infants might guide treatment., (© 2021. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.)

Rationale: The renin-angiotensin-aldosterone system is a major pathway in regulating blood pressure, glomerular filtration, and fluid homeostasis. During inflammatory diseases, generation of angiotensin II might be disturbed, leading to increased renin concentrations. Cardiac surgery and the use of cardiopulmonary bypass both induce inflammatory response and cardiovascular instability, which can contribute to acute kidney injury (AKI). Objectives: To investigate whether renin concentrations are associated with hypotension and AKI. Methods: This is a single-center, prospective, observational study among patients undergoing cardiac surgery. Measurements and Main Results: The primary endpoint was the occurrence of AKI within 72 hours after cardiac surgery. A total of 197 patients were available for the primary analysis. The median renin serum concentration was 40.2 μU/ml (quartile 1 [Q1]-Q3, 9.3-144.4) at baseline and 51.3 μU/ml (Q1-Q3, 19.1-167.0) 4 hours after cardiac surgery, whereas the difference between postoperation and preoperation concentrations (Δ-renin) was 3.7 μU/ml (Q1-Q3, -22.7 to 50.9). Patients with an elevated Δ-renin developed an AKI significantly more often (43% vs. 12.2%; P  < 0.001). High Δ-renin after cardiac surgery was associated with a significantly lower mean arterial pressure, longer time on vasopressors, and longer length of ICU and hospital stay. The area under the curve (AUC) of Δ-renin for the prediction of AKI (AUC, 0.817; 95% confidence interval, 0.747-0.887) was significantly greater compared with the AUC of the postoperative renin concentrations (AUC, 0.702; 95% CI, 0.610-0.793; P  = 0.007). Conclusions: Elevated renin concentrations were associated with cardiovascular instability and increased AKI after cardiac surgery. Elevated renin concentrations could be used to identify high-risk patients for cardiovascular instability and AKI who would benefit from timely intervention that could improve their outcomes.

Pannexin 1 (Panx1) channels export ATP and may contribute to increased concentration of the vasodilator ATP in plasma during hypoxia in vivo. We hypothesized that Panx1 channels and associated ATP export contribute to hypoxic vasodilation, a mechanism that facilitates the matching of oxygen delivery to metabolic demand of tissue. Male and female mice devoid of Panx1 ( Panx1 -/- ) and wild-type controls (WT) were anesthetized, mechanically ventilated, and instrumented with a carotid artery catheter or femoral artery flow transducer for hemodynamic and plasma ATP monitoring during inhalation of 21% (normoxia) or 10% oxygen (hypoxia). ATP export from WT vs. Panx1 -/- erythrocytes (RBC) was determined ex vivo via tonometer experimentation across progressive deoxygenation. Mean arterial pressure (MAP) was similar in Panx1 -/- ( n = 6) and WT ( n = 6) mice in normoxia, but the decrease in MAP in hypoxia seen in WT was attenuated in Panx1 -/- mice (-16 ± 9% vs. -2 ± 8%; P < 0.05). Hindlimb blood flow (HBF) was significantly lower in Panx1 -/- ( n = 6) vs. WT ( n = 6) basally, and increased in WT but not Panx1 -/- mice during hypoxia (8 ± 6% vs. -10 ± 13%; P < 0.05). Estimation of hindlimb vascular conductance using data from the MAP and HBF experiments showed an average response of 28% for WT vs. -9% for Panx1 -/- mice. Mean venous plasma ATP during hypoxia was 57% lower in Panx1 -/- ( n = 6) vs. WT mice ( n = 6; P < 0.05). Mean hypoxia-induced ATP export from RBCs from Panx1 -/- mice ( n = 8) was 82% lower than that from WT ( n = 8; P < 0.05). Panx1 channels participate in hemodynamic responses consistent with hypoxic vasodilation by regulating hypoxia-sensitive extracellular ATP levels in blood. NEW & NOTEWORTHY Export of vasodilator ATP from red blood cells requires pannexin 1. Blood plasma ATP elevations in response to hypoxia in mice require pannexin 1. Hemodynamic responses to hypoxia are accompanied by increased plasma ATP in mice in vivo and require pannexin 1.

Intradialytic hypotension (IDH) is a hemodynamic phenomenon recently associated with decreased blood oxygen saturation (SO 2 ). The ratio between peripheral oxygen saturation (SpO 2 ) and central venous SO 2 (ScvO 2 ) or Oxygen Extraction Ratio (OER), which represents a roughly estimate of the amount of oxygen claimed by peripheral tissues, might be used to estimate haemodialysis (HD) related hypoxic stress. Aim of this pilot study was to evaluate the relationship between OER increments during dialysis sessions (ΔOER) and episodes of IDH. We enrolled chronic HD patients with permanent central venous catheter (CVC) and no fistula, in whom ScvO 2 measurement is at hand. OER ([(SpO 2  - ScvO 2 )/SpO 2 ] × 100) was measured in three consecutive HD sessions (HD OER sessions) before HD, after 15', 30' and 60' min and at the end of HD. Then, a one-year follow-up was planned to record the number of IDH episodes. In the 28 enrolled patients (age 74 ± 2.6 years), during 12 ± 1.2 months of follow up, incidence of IDH was 3.6%. We divided patients into two groups, above or below the median value of ΔOER at the end of HD, which was 36%. In these groups, the average incidence of IDH was 7% and 2% respectively (p < 0.01), while OER values before HD were not different. Notably, in the high ΔOER group the OER increment was evident since after 15' and was significantly higher than in the low ∆OER group (∆OER-15' = 19 ± 3.0% vs. 9.0 ± 3.0%; p < 0.05). By comparison, blood volume changes overlapped in the two groups (average change - 9 ± 0.8%). Values of ∆OER > 19% after only 15' of HD treatment or > 36% at the end of the session characterize patients with higher rates of hypotension. Intradialytic ∆OER, a parameter of tissue hypoxic stress, identifies more fragile patients at greater risk of IDH.

Angiotensin-(1-7) [Ang-(1-7)]/Mas receptor is a counter-regulatory axis that counteracts detrimental renin-angiotensin system (RAS) effects, especially regarding systemic inflammation, vasopressin (AVP) release, and hypothalamic-pituitary-adrenal (HPA) activation. However, it is not completely understood whether this system may control centrally or systemically the late phase of systemic inflammation. Thus, the aim of this study was to determine whether intracerebroventricular (i.c.v.) administration of Ang-(1-7) can modulate systemic inflammation through the activation of humoral pathways in late phase of endotoxemia. Endotoxemia was induced by systemic injection of lipopolysaccharide (LPS) (1.5 mg/kg, i.v.) in Wistar rats. Ang-(1-7) (0.3 nmol in 2 µL) promoted the release of AVP and attenuated interleukin-6 (IL-6) and nitric oxide (NO) levels but increased interleukin-10 (IL-10) in the serum of the endotoxemic rats. The central administration of Mas receptor antagonist A779 (3 nmol in 2 µL, i.c.v.) abolished these anti-inflammatory effects in endotoxemic rats. Furthermore, Ang-(1-7) applied centrally restored mean arterial blood pressure (MABP) without affecting heart rate (HR) and prevented vascular hyporesponsiveness to norepinephrine (NE) and AVP in animals that received LPS. Together, our results indicate that Ang-(1-7) applied centrally promotes a systemic anti-inflammatory effect through the central Mas receptor and activation of the humoral pathway mediated by AVP.

Background: Previous studies have defined preshock as isolated hypotension or isolated hypoperfusion, whereas shock has been variably defined as hypoperfusion with or without hypotension. We aimed to evaluate the mortality risk associated with hypotension and hypoperfusion at the time of admission in a cardiac intensive care unit population., Methods: We analyzed Mayo Clinic cardiac intensive care unit patients admitted between 2007 and 2015. Hypotension was defined as systolic blood pressure <90 mm Hg or mean arterial pressure <60 mm Hg, and hypoperfusion as admission lactate >2 mmol/L, oliguria, or rising creatinine. Associations between hypotension and hypoperfusion with hospital mortality were estimated using multivariable logistic regression., Results: Among 10 004 patients with a median age of 69 years, 43.1% had acute coronary syndrome, and 46.1% had heart failure. Isolated hypotension was present in 16.7%, isolated hypoperfusion in 15.3%, and 8.7% had both hypotension and hypoperfusion. Stepwise increases in hospital mortality were observed with hypotension and hypoperfusion compared with neither hypotension nor hypoperfusion (3.3%; all P <0.001): isolated hypotension, 9.3% (adjusted odds ratio, 1.7 [95% CI, 1.4-2.2]); isolated hypoperfusion, 17.2% (adjusted odds ratio, 2.3 [95% CI, 1.9-3.0]); both hypotension and hypoperfusion, 33.8% (adjusted odds ratio, 2.8 [95% CI, 2.1-3.6]). Adjusted hospital mortality in patients with isolated hypoperfusion was higher than in patients with isolated hypotension ( P =0.02) and not significant different from patients with both hypotension and hypoperfusion ( P =0.18)., Conclusions: Hypotension and hypoperfusion are both associated with increased mortality in cardiac intensive care unit patients. Hospital mortality is higher with isolated hypoperfusion or concomitant hypotension and hypoperfusion (classic shock). We contend that preshock should refer to isolated hypotension without hypoperfusion, while patients with hypoperfusion can be considered to have shock, irrespective of blood pressure.

Background: Intradialytic hypotension (IDH) is a common serious complication in hemodialysis (HD) patients. Hyperphosphatemia is also common in HD patients and promotes vascular calcification. Given the association between vascular calcification and IDH, we investigated the association between IDH and serum phosphorus in HD patients., Methods: We enrolled 173 patients who received HD for 3 months or more. IDH was defined as a nadir systolic blood pressure (SBP) <90 mm Hg or as a decrease in SBP ≥20 mm Hg or a decrease in mean arterial pressure by 10 mm Hg with the occurrence of hypotension-related symptoms requiring intervention. Serum phosphorus levels were analyzed both as a continuous variable and as a categorical variable., Results: IDH occurred in 40 (23.1%) of the 173 patients. The mean phosphorus level was 4.9 mg/dL. A 1 mg/dL higher serum phosphorus resulted in a 2.1-fold greater odds of IDH. The fully adjusted odds ratio (OR) and 95% confidence interval (CI) were 2.11 (1.48-3.01). High categorized phosphorus levels were also associated with IDH. The highest tertile of serum phosphorus was associated with 6.5-fold greater odds of developing IDH compared to the referent group (the middle tertile of serum phosphorus, 4.0-<5.3 mg/dL); the fully adjusted OR (95% CIs) were 6.53 (2.23-19.09). In subgroup analyses, diabetes and pre-dialysis SBP modified the association between IDH and phosphorus levels, with a more pronounced association in diabetic patients and pre-dialysis SBP ≥140 mm Hg., Conclusion: In HD patients, higher phosphorus levels were associated with an increased occurrence of IDH., (© 2021 S. Karger AG, Basel.)

The hypoxic fetus is at greater risk of cardiovascular demise during a challenge, but the reasons behind this are unknown. Clinically, progress has been hampered by the inability to study the human fetus non-invasively for long period of gestation. Using experimental animals, there has also been an inability to induce gestational hypoxia while recording fetal cardiovascular function as the hypoxic pregnancy is occurring. We use novel technology in sheep pregnancy that combines induction of controlled chronic hypoxia with simultaneous, wireless recording of blood pressure and blood flow signals from the fetus. Here, we investigated the cardiovascular defense of the hypoxic fetus to superimposed acute hypotension. Pregnant ewes carrying singleton fetuses surgically prepared with catheters and flow probes were randomly exposed to normoxia or chronic hypoxia from 121±1 days of gestation (term ≈145 days). After 10 days of exposure, fetuses were subjected to acute hypotension via fetal nitroprusside intravenous infusion. Underlying in vivo mechanisms were explored by (1) analyzing fetal cardiac and peripheral vasomotor baroreflex function; (2) measuring the fetal plasma catecholamines; and (3) establishing fetal femoral vasoconstrictor responses to the α 1 -adrenergic agonist phenylephrine. Relative to controls, chronically hypoxic fetal sheep had reversed cardiac and impaired vasomotor baroreflex function, despite similar noradrenaline and greater adrenaline increments in plasma during hypotension. Chronic hypoxia markedly diminished the fetal vasopressor responses to phenylephrine. Therefore, we show that the chronically hypoxic fetus displays markedly different cardiovascular responses to acute hypotension, providing in vivo evidence of mechanisms linking its greater susceptibility to superimposed stress.

Background: Ondansetron has been shown to reduce the incidence of hypotension and vasopressor requirement during spinal anesthesia for obstetric and nonobstetric surgery. However, the magnitude of this effect has not been fully quantified. In this parallel-group, randomized, double-blinded study, we determined the effective dose in 50% of subjects (ED50) of a prophylactic phenylephrine infusion for preventing hypotension in patients who received a single dose of intravenous ondansetron 4 mg or saline control before combined spinal-epidural anesthesia for elective cesarean delivery. ED50 values obtained were compared to estimate the effect of ondansetron versus placebo on vasopressor requirement., Methods: Sixty parturients were randomly assigned to receive ondansetron (group O) or saline control (group C) 10 minutes before positioning for induction of spinal anesthesia. A prophylactic phenylephrine infusion was used to prevent hypotension. The first patient in each group received a phenylephrine infusion at the rate of 0.5 µg/kg/min. The infusion rate for each subsequent patient was varied with increments or decrements of 0.05 µg/kg/min based on the response of the previous patient, and the effective dose of the phenylephrine infusion for preventing hypotension in 50% of patients (ED50) was calculated for each group and compared using up-down sequential analysis. Probit regression was applied as a backup and sensitivity analysis was used to compare ED50 values for phenylephrine between groups by comparing calculated relative mean potency., Results: The ED50 (mean [95% confidence interval (CI)]) of the rate of phenylephrine infusion was lower in group O (0.24 µg/kg/min [0.10-0.38 µg/kg/min]) compared with group C (0.32 µg/kg/min [0.14-0.47 µg/kg/min]) (P < .001). The total consumption of phenylephrine (mean ± standard deviation [SD]) until delivery was lower in group O (316.5 ± 25.9 µg) than in group C (387.7 ± 14.7 µg, P = .02). The estimate of relative median potency for phenylephrine for group O versus group C was 0.74 (95% CI, 0.37-0.95)., Conclusions: Under the conditions of this study, intravenous ondansetron 4 mg reduced the ED50 of a prophylactic phenylephrine infusion by approximately 26% in patients undergoing cesarean delivery under combined spinal-epidural anesthesia.

Background: Hypotension and/or hypocapnia might increase general anesthesia (GA)-related neuromorbidity in infants, but safe levels of perioperative blood pressure are poorly defined. Serum protein S100b has been used as screening, monitoring, and prediction tool in the management of patients with traumatic brain injury. Using an animal model, we investigated serum S100b as an acute biomarker of cerebral hypoperfusion and cerebral cell dysfunction during hypotension, hypocapnia, or combined hypotension/hypocapnia during GA., Methods: Fifty-seven sevoflurane-midazolam anesthetized piglets aged 4 to 6 weeks were randomly allocated to control (n=9), hypotension (n=18), hypocapnia (n=20), or combined hypotension and hypocapnia (n=10). Hypotension (target mean arterial blood pressure: 35 to 38 or 27 to 30 mm Hg) was induced by blood withdrawal and nitroprusside infusion, and hypocapnia by hyperventilation (target PaCO2: 28 to 30 and 23 to 25 mm Hg). Serum S100b and albumin were measured at baseline, before and 60 minutes after the interventions, and following 60-minute recovery., Results: Serum S100b concentrations decreased over time (P=0.001), but there was no difference in S100b between control piglets and those exposed to hypotension, hypocapnea, or a combination of the both (P=0.105). Albumin decreased in all 4 groups (P=0.001)., Conclusion: S100b did not increase following 60 minutes of systemic hypotension and/or hypocapnia during GA in piglets. In this setting, the use of S100b as a biomarker of cerebral cell tissue dysfunction cannot be supported.

Objective: The aim of this study is to compare a point-of-care (POC) analysis, Enterprise POC (epoc), using the capillary blood obtained from skin puncture with conventional laboratory tests using arterial and venous blood in hypotensive patients., Methods: This study was conducted at the emergency department of a tertiary care hospital between June and November 2018. 231 hypotensive patients were enrolled. Three types of blood samples (capillary blood from skin puncture and arterial and venous blood from blood vessel puncture) were collected and analyzed. We compared a total of 13 parameters (pH, pCO2, pO2, HCO3-, Ca2+, lactate, Na+, K+, Cl-, glucose, Hb, Hct, and creatinine) between the POC analysis and reference analyzers by performing the equivalence test and Bland-Altman plot analysis., Results: In hypotensive patients, with the exception of two parameters (pCO2, pO2), the pH, HCO3-, Ca2+, lactate, Na+, K+, Cl-, glucose, Hb, Hct, and creatinine parameters measured by the POC analysis were equivalent to or correlated with the reference values. In the patients with cardiac arrest group, nine parameters (pH, HCO3-, Ca2+, Na+, K+, glucose, Hb, Hct, and creatinine) analyzed by the epoc system were equivalent to the reference values., Conclusion: Most parameters, except pO2, measured by the epoc system using the capillary blood in hypotensive patients were equivalent to or correlated with those measured by the reference analyzers., (Copyright © 2019. Published by Elsevier Inc.)

Purpose: MTS is elicited during open abdominal surgery and is characterized by facial flushing, hypotension, and tachycardia in response to the release of prostacyclin (PGI 2 ) to plasma. MTS seems to affect postoperative morbidity, but data from larger cohorts are lacking. We aimed to determine the impact of severe mesenteric traction syndrome (MTS) on postoperative morbidity in patients undergoing open upper gastrointestinal surgery., Methods: The study was a secondary analysis of data from three cohorts (n = 137). The patients were graded for severity of MTS intraoperatively, and hemodynamic variables and blood samples for plasma 6-keto-PGF 1α , a stable metabolite of PGI 2 , were obtained at defined time points. Postoperative morbidity was evaluated by the comprehensive complication index (CCI) and the Dindo-Clavien classification (DC)., Results: Patients undergoing either esophagectomy (n = 70), gastrectomy (n = 22), liver- (n = 23), or pancreatic resection (n = 22) were included. Severe MTS was significantly associated with increased postoperative morbidity, i.e., CCI ≥ 26.2 (OR 3.06 [95% CI 1.1-6.6]; p = 0.03) and risk of severe complications, i.e., DC ≥3b (OR 3.1 [95% CI 1.2-8.2]; p = 0.023). Furthermore, patients with severe MTS had increased length of stay (OR 10.1 [95% CI 1.9-54.3]; p = 0.007) and were more likely to be admitted to the intensive care unit (OR = 7.3 [95% CI 1.3-41.9]; p = 0.027), but there was no difference in 1-year mortality., Conclusion: Occurrence of severe MTS during upper gastrointestinal surgery is associated with increased postoperative morbidity as indicated by an increased rate of severe complications, length of stay, and admission to the ICU. It remains to be determined whether inhibition of MTS enhances postoperative recovery.

Military prehospital care for hemorrhage is often characterized by use of tourniquets (TQ) and permissive hypotensive resuscitation (PHR) with crystalloids or colloids, but these treatments have not been previously combined in an animal model. Although albumin resuscitation solutions have been tested, the potential effects of nonesterified fatty acids (NEFAs) bound to albumin have not been evaluated in vivo, and few studies have investigated concentrated albumin solutions to reduce fluid requirements. We created a militarily relevant rat model of trauma and hemorrhagic shock (T/HS) (27 mL/kg hemorrhage) with TQ and PHR. We investigated the ability of resuscitation with concentrated (250 mg/mL) albumin, followed by Plasmalyte as needed to maintain PHR, to reduce fluid volumes (vs. Plasmalyte alone, N = 17). Albumin was free of nonesterified fatty acids (N = 15) or saturated with oleic acid (OA; N = 13). The model resulted in high (53%) mortality within 3 h of injury. Only OA-saturated albumin was able to significantly reduce mortality (from 47% to 8%) and fluid requirements (from 56 to 6 mL/kg) compared to Plasmalyte alone. Plasma NEFA-binding capacity was saturated earliest in the OA-saturated albumin group. Likewise, OA-saturated albumin tended to increase cell-free hemoglobin in the broncheoalveolar lavage fluid, which was significantly associated with survival. Our findings suggest incorporating TQ and PHR in T/HS models may result in high mortality and fluid requirements and that OA-saturated albumin, but not NEFA-free albumin or Plasmalyte alone, may provide a benefit to early survival and resuscitation volume, though a hemolytic mechanism may have later consequences, so caution is advised.

Background Hemodialysis patients are at risk of intradialytic hypotension (IDH), which is associated with mortality and cardiovascular and neurological events. The use of biomarkers of volemia such as relative change in protidemia and BNP (B-natriuretic peptide) levels to predict IDH remains unknown. Methods and Results We conducted a prospective observational study, which enrolled 170 chronic hemodialysis patients in a single center from September 2015 to March 2016. BNP and the relative change of protidemia level (Δprotidemia=postdialysis protidemia-predialysis protidemia) were measured monthly over 6 months. A logistic mixed regression model was used to define the best biomarkers that predict the 30-day risk of IDH. Receiver operating characteristic analysis area under the curve was used to define the cutoff values of Δprotidemia that predict IDH A logistic mixed model reveals that Δprotidemia predicts the 30-day risk of IDH but not BNP or age; odds ratio=1.12, 95% CI 1.08-1.17), odds ratio=0.81, 95% CI (0.64; 1.07) and odds ratio =0.015 95% CI (0.99; 1.03), respectively. Adding the ultrafiltration rate did not improve the model. A receiver operating characteristic curve analysis showed that Δprotidemia of 10 g/L allowed for discrimination of the patients with IDH (area under the curve= 0.67; 95% CI 0.62-0.72, P <0.05). There was an increase in area under the curve to 0.71 (95% CI 0.63-0.76) in a subgroup of hemodialysis with BNP <300 ng/L, for a cutoff value of 11 g/L, especially for the nondiabetic patients. Conclusions Relative change in protidemia level (Δprotidemia) outperforms BNP and ultrafiltration rate as a predictor for 30-day risk of IDH. These results should be confirmed by a prospective study.

Background: Hypocapnia is a common alteration during anesthesia in neonates., Aim: To investigate the effects of hypocapnia and hypocapnia combined with hypotension (HCT) on cerebral perfusion and tissue oxygenation in anesthetized piglets., Method: Thirty anesthetized piglets were randomly allocated to groups: moderate hypocapnia (mHC), severe hypocapnia (sHC), and HCT. Cerebral monitoring comprised a tissue oxygen partial pressure and a laser Doppler probe inserted into the brain tissue as well as a near-infrared spectroscopy (NIRS) sensor placed on the skin, measuring regional oxygen saturation. Hypocapnia was induced by hyperventilation (target PaCO 2 mHC: 3.7-4; sHC: 3.1-3.3 kPa) and hypotension by blood withdrawal and nitroprusside infusion (mean blood pressure: 35-38 mm Hg). Data were analyzed at baseline, during (Tr20, Tr40, Tr60) and after (Post20, Post40, Post60) treatment., Results: Compared to baseline, tissue oxygen partial pressure decreased significantly and equally during all treatments (mean [SD] at baseline: mHC 35.7 [32.45]; sHC: 28.1 [20.24]; HCT 25.4 [10.3] and at Tr60: mHC: 29.9 [27.36]; sHC: 22.2 [18.37]; HCT: 18.4 [9.5] mm Hg). Decreased laser Doppler flow was detected with all treatments at Tr20 (mHC: 0.9 [0.18]; sHC: 0.88 [0.15]; HCT: 0.97 [0.13] proportion from baseline). Independently of group, regional oxygen saturation varied only after reverting and not during treatment. Blood lactate, pH, HCO 3 - , and PaO 2 increased during treatment with no differences between groups., Conclusion: This animal model revealed reduced cerebral blood flow and brain tissue oxygenation during hypocapnia without detectable changes in regional oxygen saturation as measured by NIRS. Changes occurred as early as during moderate hypocapnia., (© 2019 John Wiley & Sons Ltd.)

Intradialytic hypotension is a major complication during hemodialysis session, associated with increased risk of cardiovascular events and mortality. Its pathophysiology is believed to be multifactorial and remains not well elucidated. The aim of this study is to put forward new mechanisms behind the development of intradialytic hypotension. The study included sixty-five subjects on chronic hemodialysis, divided into two groups: intradialytic hypotensive (n=12) and normotensive (n=53), according to the variation of systolic blood pressure between post-dialysis and pre-dialysis measurements. Renin and angiotensin converting enzyme I plasma concentrations increased in both groups but more likely in normotensive group. Aldosterone plasma concentration is increased in the normotensive group while it decreased in the intradialytic hypotension group. Plasma endothelin concentrations showed higher values in intradialytic hypotension group. Post-dialysis asymmetric dimethylarginine and angiotensin converting enzyme 2 plasma concentrations were significantly higher in intradialytic hypotension group as compared to normotensive one. Collectrin plasma concentrations were significantly lower in intradialytic hypotension group. Finally, post-dialysis vascular endothelial growth factor C plasma concentration significantly increased in intradialytic hypotension group. In conclusion, endothelial dysfunction characterized by a lower level of vasoactive molecule seems to play a critical role in intradialytic hypotension development.

Purpose of Review: Neurological complications after cardiac surgery remain prevalent. This review aims to discuss the modifiable and outcome-relevant risk factors based on an up-to-date literature review, with a focus on interventions that may improve outcomes., Recent Findings: There is a close relationship between intraoperative blood pressure and postoperative neurological outcomes in cardiac surgical patients based on cohort studies and randomized controlled trials. Adopting an optimal and personalized blood pressure target is essential; however, the outstanding issue is the determination of this target. Maintaining cerebral tissue oxygen saturation at least 90% patient's baseline during cardiac surgery may be beneficial; however, the outstanding issues are effective intervention protocols and quality outcome evidence. Maintaining hemoglobin at least 7.5 g/dl may be adequate for cardiac surgical patients; however, this evidence is based on the pooled results of thousands of patients. We still need to know the optimal hemoglobin level for an individual patient, which is of particular relevance during the decision-making of transfusion or not., Summary: The available evidence highlights the importance of maintaining optimal and individualized blood pressure, cerebral tissue oxygen saturation and hemoglobin level in improving neurological outcomes after cardiac surgery. However, outstanding issues remain and need to be addressed via outcome-oriented further research.

Intradialytic hypotension (IDH) is related to high morbidity and mortality. There is evidence that arginine-vasopressin (AVP) responses could play a role. Copeptin is a reliable biomarker of AVP. In this study, copeptin, aldosterone, epinephrine, and norepinephrine levels in patients with IDH were evaluated throughout a hemodialysis (HD) session and compared with the control group. The study includes 15 patients who were normotensive during HD and 15 patients with IDH with a minimum HD vintage of 1 year. Blood samples were collected before the initiation of an HD session (T 0 ), in the mid-session for control group, 30 min after mean arterial pressure drop for IDH patients (T 1 ), and at the end of the session (T 2 ). Groups had similar demographic features and health parameters, interdialytic weight gains, and ultrafiltration amounts. The IDH group had a mean arterial pressure decline of 39.9 (±6.4) mm Hg. Copeptin levels of the control group increased an average of 79.9 (±97.5) pmol/L at T 1 and an additional 24.8 (±33.9) pmol/L at T 2 . In the IDH group, copeptin level increases at T 1 and T 2 were 3.2 (±5.5) pmol/L and 34 (±44.6) pmol/L, respectively . Copeptin levels of the IDH group were significantly lower at T 1 (P < 0.001) and at the T 0 -T 2 interval than control group (P = 0.05). In the control group, aldosterone levels distinctly decreased, and in the IDH group, aldosterone levels were elevated (P < 0.001). Small changes were detected in epinephrine and norepinephrine levels for both groups but did not reach significance (P = 0.6 and P = 0.3, respectively). Lower copeptin level alterations suggest inadequate AVP responses in patients with IDH., (© 2018 International Society for Apheresis, Japanese Society for Apheresis, and Japanese Society for Dialysis Therapy.)

Purpose: Raised serum uric acid, a marker of oxidative stress, is known to increase vascular tone and depress myometrial contractility. A rise in serum uric acid levels has also been reported during labor, warranting its correlation with post-spinal hypotension and uterine tone., Methods: Serum UA sample was drawn from enrolled healthy, laboring parturients. Of these, 100 women who required emergency cesarean delivery were re-sampled prior to surgery. Following spinal anesthesia we recorded episodes of hypotension (MAP < 80% of baseline), use of vasopressors and supplemental uterotonics. The primary outcome was maternal hyperuricemia (1SD > appropriate for gestation age) and its correlation with post-spinal hypotension. Secondary outcomes were total vasopressors used, duration of labor and its effect on uric acid levels, uterine tone and neonatal outcome., Results: Hyperuricemia was observed in 33% of parturients. On comparing with women showing normal uric acid levels, hyperuricemic parturients experienced significantly lower incidence of post-spinal hypotension (45.5% vs. 67.2%; p value = 0.04) and lower vasopressor usage (p value = 0.06). Clinically, an increased use of supplemental uterotonics in these parturients was noted (p = 0.20). The duration of labor had no impact on uric acid levels. Neonatal outcome was unaffected., Conclusions: In healthy, normotensive parturients undergoing emergency cesarean delivery, maternal hyperuricemia is associated with lower incidence of post-spinal hypotension and reduced need of vasopressors. Elevated serum uric acid levels may also be associated with decreased uterine tone, necessitating greater requirement of supplemental uterotonics. However, further prospective trials are needed to strongly establish this association.

Complement (C) activation can underlie the infusion reactions to liposomes and other nanoparticle-based medicines, a hypersensitivity syndrome that can be partially reproduced in animal models. However, the sensitivities and manifestations substantially differ in different species, and C activation may not be the only cause of pathophysiological changes. In order to map the species variation of C-dependent and -independent pseudoallergy (CARPA/CIPA), here we used known C activators and C activator liposomes to compare their acute hemodynamic, hematological, and biochemical effects in rats. These C activators were cobra venom factor (CVF), zymosan, AmBisome (at 2 doses), its amphotericin B-free vehicle (AmBisombo), and a PEGylated cholesterol-containing liposome (PEG-2000-chol), all having different powers to activate C in rat blood. The pathophysiological endpoints measured were blood pressure, leukocyte and platelet counts, and plasma thromboxane B2, while C activation was assessed by C3 consumption using the Pan-Specific C3 assay. The results showed strong linear correlation between C activation and systemic hypotension, pointing to a causal role of C activation in the hemodynamic changes. The observed thrombocytopenia and leukopenia followed by leukocytosis also correlated with C3 conversion in case of C activators, but not necessarily with C activation by liposomes. These findings are consistent with the double hit hypothesis of hypersensitivity reactions (HSRs), inasmuch as strong C activation can fully account for all symptoms of HSRs, but in case of no-, or weak C activators, the pathophysiological response, if any, is likely to involve other activation pathways.

Background: Postprandial hypotension (PPH) occurs frequently in the elderly and patients with type 2 diabetes, and lacks a satisfactory treatment. Gastric distension and the α-glucosidase inhibitor, acarbose, may attenuate the postprandial fall in blood pressure (BP) by complementary mechanisms. We aimed to determine whether gastric distension and acarbose have additive effects to attenuate the fall in BP induced by oral sucrose., Methods: Ten healthy older adults (74.0 ± 1.4 yr) had measurements of BP and superior mesenteric artery (SMA) blood flow for 120 min after receiving either (i) the 'study drink' of 100 g sucrose in 300 mL of water (control treatment), (ii) a 300 mL water 'preload' 15 min before the 'study drink' (distension treatment), (iii) 100 mg acarbose dissolved in the 'study drink' (acarbose treatment) or (iv) a 300 ml water 'preload' 15 min before 100 mg acarbose dissolved in the 'study drink' (acarbose and distension treatment)., Results: The area under the curve (AUC) 0-120min for mean arterial pressure (MAP) was greater (P = 0.005) and the maximum fall in MAP was less (P = 0.006) during treatments with acarbose. Gastric distension did not affect the MAP-AUC 0-120min response to acarbose (P = 0.44) and there was no effect of gastric distension alone (P = 0.68). Both acarbose treatments attenuated the rise in SMA blood flow (P = 0.003), whereas gastric distension had no effect., Conclusions: In healthy older adults, acarbose (100 mg), but not gastric distension, attenuates the fall in BP and rise in SMA blood flow after oral sucrose. The observations support the use of acarbose, but not gastric distension, to attenuate a postprandial fall in BP., Trial Registration: The study was retrospectively registered at ( ACTRN12618000152224 ) on February 02nd 2018.

Prompt diagnosis and timely treatment are important for reducing morbidity and mortality from pyogenic liver abscess (PLA). The purpose of this study was to investigate the importance of the delta neutrophil index (DNI) reflecting the fraction of immature granulocytes as a predictor of the development of in-hospital hypotension in initially stable patients with PLA. We retrospectively identified 308 consecutive patients (>18 years) who were hemodynamically stable at presentation and diagnosed with PLA in the emergency department (ED) between January 2011 and September 2017. The outcome of interest was in-hospital hypotension 1-24 hours after admission to the ED. A high DNI at ED admission was an independent predictor of the development of in-hospital hypotension in initially stable patients with PLA (odds ratio [OR]: 1.44, 95.0% confidence interval [CI]: 1.06-1.95; P = 0.02). A DNI > 3.3% was associated with in-hospital hypotension at ED admission (OR: 5.37, 95.0% CI: 2.91-9.92; P < 0.001). The development of in-hospital hypotension was associated with an increased risk of 30-day mortality (HR: 8.55, 95.0% CI: 2.57-28.4; P < 0.001). A high DNI independently predicts the development of in-hospital hypotension in initially stable patients with PLA. In-hospital hypotension is associated with an increased risk of 30-day mortality.

Background: There is a dearth and inconsistency of data on the role of the autonomic nervous system (ANS) in the development of arterial hypotension. Also, little is known about the involvement of endothelial factors in the development of this disease. The aim of the study was to investigate the role of the ANS and endothelial factors or vasoregulators in the development of primary arterial hypotension (PAH) in children., Methods: The cardiointervalography and clino-orthostatic test results of 113 children with PAH were compared with 88 healthy children of comparable age (7-11 years). Serum endothelial factors (nitric oxide and endothelins) of all children were measured., Results: The findings revealed that children with PAH had higher activity of the sympathetic (p<0.001) and parasympathetic (p<0.001) divisions of the ANS at the initial (resting) position of clino-orthostatic test. The activity of these divisions of the autonomic nervous system correlated with the activity of a cardiac pacemaker. The change of position from horizontal into vertical was accompanied by a rise only in sympathetic activity (p<0.001). However, there was a decline in the sympathetic nervous system (p<0.001) compared to the indices of the initial (resting) position registered in the tenth minute of the vertical position. The parasympathetic division of the ANS based on heart rate variability showed high activity in all positions of the clino-orthostatic test in the patients with PAH compared with healthy children. The activity of the parasympathetic nervous system was associated with increased synthesis of endothelial factors (nitric oxide and endothelins) in blood., Conclusions: The inadequate response of the autonomic nervous system to the clino-orthostatic test in children with PAH is associated with disorders of both divisions of the autonomic nervous system as well as vascular endothelial factors., (Copyright © 2018 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.)

Introduction: Supra-clinical doses of clonidine appear beneficial in experimental sepsis, but there is limited understanding of the effects of clonidine at clinically relevant doses., Methods: In conscious sheep, with implanted renal and pulmonary artery flow probes, sepsis was induced by infusion of live Escherichia coli. At 24 h, a high clinical dose of clonidine (HCDC) [1.0 μg/kg/h], a low clinical dose of clonidine (LCDC) [0.25 μg/kg/h] or vehicle, was infused for 8 h., Results: Animals developed hyperdynamic, hypotensive sepsis with acute kidney injury. The HCDC decreased heart rate (153 ± 6 to 119 ± 7 bpm) and cardiac output (5.6 ± 0.4 to 5.0 ± 0.4 L/min), with no reduction in mean arterial pressure (MAP). In contrast, LCDC increased cardiac output with peripheral vasodilatation. Both doses induced a large transient increase in urine output, an increase in plasma osmolality and, with the high dose, an increase in plasma arginine vasopressin. Sepsis increased plasma interleukin-6 (IL-6) and IL-10 and clonidine further increased IL-10 (1.6 ± 0.1 to 3.3 ± 0.7 ng/mL), but not IL-6. Clonidine reduced rectal temperature. During recovery from sepsis, MAP returned to baseline values more rapidly in the HCDC group (P < 0.001)., Conclusions: In hyperdynamic, hypotensive sepsis, the effects of clonidine at clinically relevant doses are complex and dose dependent. HCDC attenuated sepsis-related increases in heart rate and cardiac output, with little effect on arterial pressure. It also induced a water diuresis, increased AVP, reduced body temperature, and had an anti-inflammatory action. Low-dose clonidine had similar but less pronounced effects, except that it induced moderate vasodilatation and increased cardiac output.

Background: Intermittent infusion hemodiafiltration is a recently developed convective method of renal replacement therapy using cyclic back-filtration infusion. Quick and regular infusion prevents intradialytic hypotension. However, the optimal dose of bolus dialysate infusion required to stabilize blood pressure has not been reported. Here, we investigated the relationship between the dose of bolus dialysate infusion and blood pressure., Summary: A total of 77 patients on maintenance hemodialysis were enrolled in this study. Dialysate was infused rapidly by backward filtration at a rate of 150 mL/min at 30-min intervals using an automated dialysis machine. The effects with two bolus infusion volumes (100 and 200 mL) were compared, each for an observation period of 2 weeks. Systolic blood pressure (SBP) was measured at the start and at the end of each dialysis session, and the highest SBP and lowest SBP measurements were also recorded. Patients were divided according to dry weight into a <52 kg group and a ≥52 kg group, and various parameters were compared between the 100 and 200 mL bolus infusion volumes in each group. Among patients in the <52 kg group, SBP did not vary at any of the time points. However, for patients in the ≥52 kg group, SBP at the end of treatment was significantly lower in the 100-mL group than in the 200-mL group (141 ± 20 vs. 144 ± 21 mm Hg, p = 0.041), and the minimum SBP was also lower in the 100-mL group than in the 200-mL group (127 ± 17 vs. 131 ± 18 mm Hg, p = 0.010). Key Messages: Among patients with a dry weight of ≥52 kg, blood pressure was more stable when a bolus fluid volume of 200 mL was used, compared with a volume of 100 mL. However, for patients with a dry weight of <52 kg, the significance of the difference in bolus fluid volumes disappeared. Thus, the replacement fluid volume might be better determined based on the patient's dry weight., Trial Registration: UMIN 000028145, Registered July 10, 2017., (© 2019 S. Karger AG, Basel.)

Background: Intradialytic hypotension (IDH) is a major challenge to safely performing haemodialysis. Blood volume depletion due to fluid removal is a major cause of hypotension, so more emphasis should be placed on finding alternative modalities to traditional constant rate ultrafiltration., Summary: Intermittent back-filtrate infusion haemodiafiltration (I-HDF) utilises purified online quality dialysate with an automated dialysis machine. A bolus of 200 mL of dialysate is repetitively infused at 30-min intervals. A pilot study with 68 hypotension-prone patients revealed that I-HDF can reduce the frequency of IDH interventions, particularly in elderly patients and patients with large interdialytic weight gain (IDWG). This was typically accompanied by an increase in intradialytic blood pressure and decreased tachycardia in the latter half of the session, suggesting reduced sympathetic stimulation during I-HDF. Protective mechanisms involved in the pathophysiology of IDH could be explained in part by the findings obtained in this pilot study. Intermittent increases in blood pressure during I-HDF may prevent venous pooling (i.e., the DeJager-Krogh phenomenon), and reduced sympathetic stimulation may maintain a physiological state less likely to induce the cardio-vagal reflex (i.e., the Bezold-Jarisch reflex). The plasma refilling rate (PRR), evaluated as the refilling fraction (RF), is unexpectedly smaller in I-HDF. However, in patients who respond, the RF is well achieved, which suggests that adequate PRR is the central physiology for preventing IDH. Patients for whom I-HDF is effective are characteristically relatively elderly and show increased IDWG. Blood pressure increment and reduced sympathetic activation in I-HDF may be a mechanism for prevention of IDH. Key Messages: Evaluating relative changes in blood volume during I-HDF will provide a new perspective for exploring appropriate ultrafiltration modification that circumvents IDH., (© 2019 S. Karger AG, Basel.)

D-dimer might be correlated with prognosis in pulmonary embolism (PE). The predictive value of plasma D-dimer for disease severity and survival was investigated in the lowest and highest D-dimer quartile among 200 patients with PE. Patients with high D-dimers were significantly more often hypotensive ( P = .001), tachycardic ( P = .016), or hypoxemic ( P = .001). Pulmonary arterial obstruction index (PAOI) values were significantly higher in the high D-dimer quartile ( P < .001). Elevated troponin I (TNI) levels ( P < .001), simplified PE severity indices ≥1 ( P < .001), right-to-left ventricular (RV/LV) diameter ratios ≥1 ( P < .001), and thrombolysis ( P = .001) were more frequent in the high D-dimer quartile. D-dimer was associated with RV/LV ratios ≥1 ( P = .021), elevated PAOI ( P < .001) or TNI levels ( P < .001), hypotension ( P < .001), tachycardia ( P = .003), and hypoxemia ( P < .001), but not with long-term all-cause mortality. D-dimer predicts disease severity but not long-term prognosis in acute PE, possibly due to a more aggressive treatment strategy in severely affected patients.

Purpose: We aimed to determine the feasibility of targeting low-normal or high-normal mean arterial pressure (MAP) after out-of-hospital cardiac arrest (OHCA) and its effect on markers of neurological injury., Methods: In the Carbon dioxide, Oxygen and Mean arterial pressure After Cardiac Arrest and REsuscitation (COMACARE) trial, we used a 2 3 factorial design to randomly assign patients after OHCA and resuscitation to low-normal or high-normal levels of arterial carbon dioxide tension, to normoxia or moderate hyperoxia, and to low-normal or high-normal MAP. In this paper we report the results of the low-normal (65-75 mmHg) vs. high-normal (80-100 mmHg) MAP comparison. The primary outcome was the serum concentration of neuron-specific enolase (NSE) at 48 h after cardiac arrest. The feasibility outcome was the difference in MAP between the groups. Secondary outcomes included S100B protein and cardiac troponin (TnT) concentrations, electroencephalography (EEG) findings, cerebral oxygenation and neurological outcome at 6 months after cardiac arrest., Results: We recruited 123 patients and included 120 in the final analysis. We found a clear separation in MAP between the groups (p < 0.001). The median (interquartile range) NSE concentration at 48 h was 20.6 µg/L (15.2-34.9 µg/L) in the low-normal MAP group and 22.0 µg/L (13.6-30.9 µg/L) in the high-normal MAP group, p = 0.522. We found no differences in the secondary outcomes., Conclusions: Targeting a specific range of MAP was feasible during post-resuscitation intensive care. However, the blood pressure level did not affect the NSE concentration at 48 h after cardiac arrest, nor any secondary outcomes.

Objective: To correlate between cortisol precursors in neonates with vasopressor resistant hypotension and demographic characteristics., Methods: We investigated 48 neonates with vasopressor-resistant hypotension. Gestation at birth ranged from 34 to 42 weeks and postnatal age from 4 to 14 days. Cortisol and precursor steroids were measured soon after the onset of volume expansion and inotropes for treatment of shock. Their concentrations were determined using liquid chromatography/mass spectrometry., Results: In neonates with vasopressor-resistant hypotension, the serum levels of cortisol were within normal nonstress range. There was a strong negative linear association between postnatal age and dehydroepiandrosterone level (r = -0.50, p < .01), which decreased with neonatal age. In addition, there was a significant positive association between gestational age at birth and 17-hydroxy-pregnenolone (r = 0.33, p = .02). No further significant associations were evident between the neonatal weight, duration of gestation or gender and of the levels of cortisol or the other steroids (p > .05). The cause of therapy-resistant hypotension did not appear to influence the steroid levels., Conclusions: Cortisol stress response is absent in these severely ill late preterm and term infants. This may be due to inhibition of the distal pathway of cortisol synthesis.

Rationale: Carotid sinus hypersensitivity (CSH) is traditionally classified into 3 subgroups: cardioinhibitory, vasodepressor, and mixed subtypes. However, the underlying mechanism of CSH in head and neck cancer is controversial. Several pathological mechanisms of CSH have been proposed: atherosclerotic noncompliance, sternocleidomastoid proprioceptive denervation, and generalized autonomic dysfunction., Patient Concerns: We reported a 75-year-old man who had recurrent syncope attacks secondary to hypotension and reduced plasma norepinephrine (NE) levels. CSH was suspected when carotid massage induced syncope-like symptom., Diagnoses: Nasopharynx carcinoma with regional lymph node involvement and CSH., Interventions: On admission, dopamine was administered to maintain the blood pressure. When NE deficiency was confirmed, intravenous NE combined with oral midodrine replaced the dopamine treatment., Outcomes: The syncopal episodes completely resolved with periodic occurrence of hypertension., Lessons: Our case suggests a potential role of carotid sinus in regulating the release of NE in adrenal gland and that the monitoring of catecholamine level is recommended in the CSH cases either from head and neck tumors or other mechanical manipulation of carotid sinus.

Objectives: Temporal relation between adrenal insufficiency and hypotension is poorly understood. We examined the association between basal and post-stimulation cortisol and death or vasopressor refractory hypotension in preterm neonates., Study Design: Prospective cohort study in ≤30 weeks' and/or <1,250 g weight. Primary outcome-composite of death or vasopressor refractory hypotension by day 14 of life. Plasma cortisol levels were measured at 24-36 h (T1), 72-84 h (T2) and 10 days (T3), and post-stimulation cortisol at T1 and later at T2 and T3 if the adrenal response was inadequate earlier., Results: Basal cortisol (µg/dl) at 24-36 h was significantly higher in the outcome group (37.2 ± 21.1 vs. 22.04 ± 14.6; mean difference (MD) (95% confidence interval (CI)): -15.1 (-23.6, -6.6); p = 0.005). High basal cortisol at 24-36 h (odds ratio (OR) (95% CI): 1.044 (1.009, 1.079); p = 0.01) and need for ventilation (OR (95% CI): 9.7 (1.2, 81.2); p = 0.04) independently increased the risk of death or vasopressor refractory hypotension., Conclusion: Preterm neonates who died or developed vasopressor refractory hypotension by day 14 had significantly elevated basal cortisol at 24-36 h of life.

Background: Biochemical diagnosis of adrenal insufficiency (AI) is difficult in the context of traumatic brain injury (TBI)., Aim: To assess the frequency and predictive factors of AI in victims of TBI from Algiers., Methods: Between November 2009 and December 2013, TBI victims had a single 8-9 am serum cortisol measurement during the acute postinjury period (0-7 days). AI was defined according to basal cortisol levels of 83, 276 and 414 nmol/L. Variables studied were TBI severity according to Glasgow coma scale, duration of intubation and coma, pupillary status, hypotension, anaemia, brain imaging findings, diabetes insipidus and medication. Insulin tolerance test was performed during the recovery phase, defining AI as peak cortisol <500 nmol/L., Results: Cortisol samples were obtained at median 3 (1-7) days from 277 patients (257M: 20F) aged 32 (18-65) years. Acute AI frequency was 8 (2.8%), 20 (21%) and 35 (37%), respectively using the three cortisol cut-offs. Factors predicting AI were diastolic hypotension, sedative medication, diabetes insipidus, skull base fracture and intraparenchymal haematoma. Mortality was highest in patients with acute cortisol <276 nmol/L (44.6% with OR for death 1.64, 95% CI 0.92-3.0, P = .12). During the recovery phase, AI was present in 3 of 3, 12 of 24, 4 of 16 and 20 of 66 patients with week 1 cortisol <83, 83-276, 277-414 and >414 nmol/L., Conclusion: Hydrocortisone replacement is advised in TBI patients with morning cortisol <276 nmol/L or those <414 nmol/L with additional risk factors for AI. As acute and subsequent AI are poorly correlated, patients with moderate/severe TBI require adrenal re-evaluation during the recovery phase., (© 2018 John Wiley & Sons Ltd.)

Aims: This study aimed to assess risk factors of intradialytic hypotension (IDH) and the association of prognosis and IDH among maintenance hemodialysis (MHD) patients., Methods: Among 293 patients, 117 were identified with IDH (more than 4 hypotensive events during 3 months). The association between IDH and survival was evaluated., Results: The incidence of IDH was 39.9%. Age, ultrafiltration rate, N-terminal pro-B-type natriuretic peptide (NT-proBNP), albumin, β2-microglobulin (β2MG), and aortic root inside diameter (AoRD) were independently associated with IDH. During the 5-year follow-up, 84 patients died with a mortality rate 5.2 per 100 person-year. IDH-prone patients had a higher all-cause mortality rate. IDH and left ventricular mass index were independent risk factors for death (HR 1.655, 95% CI 1.061-2.580; HR 1.008, 95% CI 1.001-1.016)., Conclusion: IDH is an independent risk factor for long-term mortality in MHD patients. Patients with older age, high ultrafiltration rate, high level of serum NT-proBNP and β2MG, hypoalbuminemia, and shorter AoRD are at high risk of IDH., (© 2018 S. Karger AG, Basel.)

Background: The extracorporeal removal of mediators is a rescue strategy for septic shock patients, which is still under investigation. Several techniques are available: coupled plasma filtration and adsorption (CPFA) combines plasma processing with renal replacement therapy., Methods: The study aimed to elucidate the role of both timing of initiation and intensity of treatment on the outcome, for which we retrospectively studied 52 patients. We collected the overall pre-CPFA time interval, starting from the first episode of hypotension in the wards and the volume of processed plasma (Vp), which we used as a proxy for intensity of treatment., Results: Timing of initiation did not significantly differ between survivors and non-survivors (25 vs. 27 h), while the Vp did (0.25 vs. 0.17 L/kg/session, p < 0.05). The significance of Vp was confirmed by a multiple logistic regression model., Conclusion: Our study confirms that intensity of CPFA, but not its timing of initiation, correlates with survival of septic shock patients., (© 2018 S. Karger AG, Basel.)

Aims: High cut-off (HCO) continuous veno-venous hemodialysis (CVVHD) was compared to high-flux membrane (HFM) continuous veno-venous hemodiafiltration (CVVHDF) in intensive care unit (ICU) acute kidney injury (AKI) in terms of efficiency, hemodynamic tolerance, medium-sized molecules removal, albumin loss, and inflammatory system activation., Methods: In a prospective cross-over randomized study, 10 AKI patients underwent successively HCO (Ultraflux EmiC2: β2-microglobulin [β2M] sieving coefficient [SC]: 0.9) CVVHD and HFM (Ultraflux AV1000S: β2M SC: 0.65) -CVVHDF., Results: Over the 20 sessions, hypotensive and febrile episodes, reduction rates of urea, creatinine, and β2M were similar in both modalities. Though dialysis dose was higher with CVVHDF (36 ± 4 vs. 21 ± 6 mL/Kg/h), urea, creatinine, and β2M instantaneous and plasmatic clearances did not differ except for urea at 12 h. Protein loss, superoxide anion production, cytokines, and growth factors variations were also comparable., Conclusion: HCO CVVHD is well tolerated and is as effective as HFM CVVHDF in clearance of solutes and removal of β2M. It induces neither protein loss nor overproduction of superoxide anion. Video Journal Club "Cappuccino with Claudio Ronco" at http://www.karger.com/?doi=489082., (© 2018 S. Karger AG, Basel.)

Background: The purpose of this study was to investigate grayanotoxin (GTX) levels in the blood of patients with GTX intoxication and in the consumed Rhododendron liqueur, and to determine whether there was an association between blood GTX level and the patient's clinical status., Methods: In September 2015, six patients were concurrently presented to the emergency department with various toxicity symptoms, which occurred after the consumption of Rhododendron liqueur at the same toxin concentration. Liquid chromatography-tandem mass spectrometry analysis was conducted on blood samples obtained from six cases of GTX intoxication treated in our emergency department., Results: At the initial evaluation in the emergency department, the mean arterial pressure of the patients ranged from 36.7 to 76.7 mm Hg. The concentrations of GTX-I and GTX-III in Rhododendron liqueur were 1.436 and 16.907 ng/mL, respectively. The initial blood GTX-III and GTX-I levels ranged from 2.9 to 58.0 ng/mL and the lower limit of quantification (LLOQ) to 8.33 ng/mL, respectively. After 20 h, the mean arterial pressure ranged from 76.7 to 93.3 mm Hg, while the blood GTX-III and GTX-I levels ranged from the LLOQ to 17.8 and 2.52 ng/mL, respectively., Discussion: We estimated that the minimum blood GTX-III and GTX-I levels that caused hypotension were between 17.83 and 27.3 ng/mL, and 2.52 and 4.55 ng/mL, respectively.

Background: In septic patients, it is uncertain whether isolated hyperlactatemia (lactate ≥4 mmol/L without refractory hypotension) can be used to diagnose septic shock and whether mortality rate differs from that of isolated refractory hypotension (refractory to 1000 mL or greater fluid bolus)., Aims: To compare baseline characteristics, treatments, and outcomes of participants enrolled into the Australian Resuscitation in Sepsis Evaluation (ARISE) trial according to the presence of isolated hyperlactatemia or isolated refractory hypotension., Patients: Cohort of 1,332 ARISE participants with sepsis and either isolated hyperlactatemia or isolated refractory hypotension., Methods: We performed a secondary analysis of the ARISE data, constructing a propensity score model to discriminate between hyperlactatemia and isolated refractory hypotension. We analyzed 90-day all-cause mortality using a generalized linear model and inverse propensity score weighting. We modeled length of intensive care unit (ICU) and hospital stay using time to event analyses incorporating mortality as a competing risk., Results: There were 478 participants (35.9%) with isolated hyperlactatemia and 854 (64.1%) with isolated refractory hypotension. They had similar median (interquartile range) ages (66.2 [54.2, 76.3] years vs. 65.2 [50.9, 75.5] years) and similar sources of infection. However, isolated hyperlactatemia participants had higher mean (standard deviation) baseline APACHE II scores (isolated hyperlactatemia 16.2 [6.4]) vs. 14.5 [6.4] for isolated refractory hypotension; P < 0.001). Isolated hyperlactatemia participants had a 1.7 times higher risk of 90-day mortality (propensity-weighted risk ratio; 95% confidence intervals [CI] 1.2, 2.5, P = 0.003). They were less likely to be discharged alive from ICU and hospital (propensity weighted sub-hazard ratio 0.77 (95% CI 0.64, 0.92; P < 0.005) and 0.79 (95% CI 0.66, 0.95; P = 0.01), respectively)., Conclusions: ARISE trial participants with isolated hyperlactatemia had worse adjusted 90-day mortality than those with isolated refractory hypotension. In septic patients, isolated hyperlactatemia may define greater illness severity and worse outcomes than isolated refractory hypotension.

Objective: Therapy-resistant hypotension complicates diseases in neonates. Our objective was to investigate whether lack of therapeutic response to plasma expanders and inotropes associates with serum levels of cortisol and its precursors., Methods: We investigated 96 infants with hypotension and critical neonatal disease for cortisol metabolism and are divided into responders and non-responders to plasma expanders and inotropes. Serum concentrations of steroids were analysed soon after the onset of volume expansion and inotrope treatment for shock. The 48 non-responders were treated with intravenous hydrocortisone (HC) and serum cortisol concentrations were monitored a week later., Results: The mean cortisol concentrations did not differ between the responders and non-responders: 13.6 ± 2.5 and 12.5 ± 4.5 μg/dL, respectively. Dehydroepiandrosterone (37.3 ± 19.5 versus 324.0 ± 106.3; p < 0.0001) and 17-hydroxy-pregnenolone concentrations were lower in responders than in non-responders. Dehydroepiandrosterone levels in non-responders were inversely associated with postnatal age (r = 0.50, p < 0.0001). There were no differences in 17-hydroxy-progesterone, 11-deoxy-cortisol and cortisone between the responders and non-responders. Hydrocortisone administration acutely increased blood pressure. Six non-responders who died despite HC administration had low levels of cortisol. The responders had normal serum cortisol after HC treatment., Conclusion: Precursors of cortisol, proximal to the 3β-hydroxysteroid dehydrogenase activity, accumulated in neonates with hypotension, responding to HC treatment.

As a type of primary open-angle glaucoma, normal-tension glaucoma (NTG) is a health problem that manifests itself with low intraocular pressure (IOP) levels and preserves its importance for public health care. In population-based screenings, which take the IOP levels of 21mmHg as a cut-off for the diagnosis of glaucoma, the diagnosis is usually delayed, and the treatment is started in an advanced stage by the referred ophthalmologists. NTG is associated with some autoimmune conditions and systemic diseases, such as paraproteinemia, nocturnal hypotension, and migraine. Recently, a simple and cheap test (namely the hemogram) was defined as measure of systemic inflammation, measuring the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR). A recent study displayed an altered platelet function in NTG patients. We hypothesize that an automated hemogram analysis for NLR together with IOP measurements may be used to screen NTG patients who are admitted to primary care clinics if any relationship between NTG and NLR could be demonstrated in future researches., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

The development of multiple organ failure in patients with hemorrhagic shock is significantly influenced by patient age. Adenosine monophosphate-activated protein kinase (AMPK) is a crucial regulator of energy homeostasis, which coordinates metabolic repair during cellular stress. We investigated whether AMPK-regulated signaling pathways are age-dependent in hemorrhage-induced lung injury and whether AMPK activation by 5-amino-4-imidazole carboxamide riboside (AICAR) affords lung protective effects. Male C57/BL6 young mice (3-5 mo), mature adult mice (9-12 mo), and young AMPKα1 knockout mice (3-5 mo) were subjected to hemorrhagic shock by blood withdrawing, followed by resuscitation with shed blood and lactated Ringer's solution. Plasma proinflammatory cytokines were similarly elevated in C57/BL6 young and mature adult mice after hemorrhagic shock. However, mature adult mice exhibited more severe lung edema and neutrophil infiltration, and higher mitochondrial damage in alveolar epithelial type II cells, than did young mice. No change in autophagy was observed. At molecular analysis, the phosphorylation of the catalytic subunit AMPKα1 was associated with nuclear translocation of peroxisome proliferator-activated receptor γ co-activator-α in young, but not mature, adult mice. Treatment with AICAR ameliorated the disruption of lung architecture in mice of both ages; however, effects in mature adult mice were different than young mice and also involved inhibition of nuclear factor-κB. In young AMPKα1 knockout mice, AICAR failed to improve hypotension and lung neutrophil infiltration. Our data demonstrate that during hemorrhagic shock, AMPK-dependent metabolic repair mechanisms are important for mitigating lung injury. However, these mechanisms are less competent with age.

: Postprandial hypotension (PPH) is a common condition that occurs primarily in elderly patients with type 2 diabetes mellitus (T2DM). This study aimed to assess the effectiveness of acarbose for PPH; it also investigated possible mechanisms behind PPH development. This single-blind, randomized controlled trial included 91 elderly patients with T2DM, aged between 60 and 80 years, who were inpatients at Beijing Hospital between March 2012 and November 2014. The patients were included into one of three groups: Group A, patients with T2DM without PPH; Group B, patients with T2DM with PPH receiving placebo; and Group C, patients with T2DM with PPH receiving acarbose. After an overnight fast, patients received a single dose of acarbose (100 mg) or placebo and then consumed a standardized 450 kcal meal. Blood pressure, glucose levels, heart rate (HR), and catecholamine levels were evaluated. Acarbose ameliorated PPH as determined by significant improvements in the duration and maximal fall in blood pressure (both p<0.001); however, no differences in HR and blood glucose levels were observed. In patients with PPH, blood pressure was correlated with blood glucose and HR variability values (p<0.05). Correlations between epinephrine and glucagon-like peptide-1 with blood pressure in groups A and C were largely lost in group B. Acarbose reduced postprandial blood pressure fluctuations in elderly patients with diabetes. PPH may be related to impaired autonomic nervous system function, reduced catecholamine secretion, and postprandial fluctuations in blood glucose levels., Trial Registration Number: Chinese Clinical Trial Registry ChiCTR-IPR-15006177., (Copyright © 2017 American Federation for Medical Research.)

Intradialytic hypotensive events (IDH) accompanied by deleterious decreases of the cardiac output complicate up to 25% of hemodialysis treatments. Monitoring options available to track hemodynamic changes during hemodialysis have been found ineffective to anticipate the occurrence of IDH. We have assembled opto-electronic instrumentation that uses the fluorescence of a small bolus of indocyanine green dye injected in the hemodialysis circuit to estimate cardiac output and blood volume based on indicator dilution principles in patients receiving hemodialysis. The instrument and technique were tested in 24 adult end-stage renal failure subjects during 64 hemodialysis sessions. A single calibration factor could be used across subjects and across time. Intra-subject variability of the measurements over time was <10%. Stroke volume index (SVI) (mean ± SEM = 34 ± 1 vs. 39 ± 2 mL m -2 ) and central blood volume (CBV) index (783 ± 36 vs. 881 ± 33 mL m -2 ) were lower at the beginning of the sessions in which IDH eventually occurred. Cardiac index, SVI, and CBV index decreased with hemodialysis in all treatment sessions but the decrease was more intense in the IDH sessions. We conclude that hemodynamic monitoring can be implemented in patients receiving hemodialysis with minimal disruption of the treatment and could help understand intradialytic hypotension.