ABO and Rhesus Blood Groups in Acute Puumala Hantavirus Infection.

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.

Early postoperative hemodynamic instability after heart transplantation - incidence and metabolic indicators.

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.

Cerebral oxygen saturation and autoregulation during hypotension in extremely preterm infants.

BACKGROUND: The impact of the permissive hypotension approach in clinically well infants on regional cerebral oxygen saturation (rScO2) and autoregulatory capacity (CAR) remains unknown. METHODS: Prospective cohort study of blinded rScO2 measurements within a randomized controlled trial of management of hypotension (HIP trial) in extremely preterm infants. rScO2, 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 rScO2 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 rScO2 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 rScO2 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.

Serum Phosphorus Levels are Associated with Intradialytic Hypotension in Hemodialysis Patients.

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.

Oxygen extraction ratio to identify patients at increased risk of intradialytic hypotension.

Intradialytic hypotension (IDH) is a hemodynamic phenomenon recently associated with decreased blood oxygen saturation (SO2). The ratio between peripheral oxygen saturation (SpO2) and central venous SO2 (ScvO2) 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 ScvO2 measurement is at hand. OER ([(SpO2 - ScvO2)/SpO2] × 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.

Pannexin 1 channels control the hemodynamic response to hypoxia by regulating O2-sensitive extracellular ATP in blood.

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.

Central Administration of Angiotensin-(1-7) Improves Vasopressin Impairment and Hypotensive Response in Experimental Endotoxemia.

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.

Pro-inflammatory cytokines as potential predictors for intradialytic hypotension.

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-1ß (IL-1ß) were observed in the IDH group (p < 0.001). Both TNF-α and IL-1ß positively correlated with predialysis BP (p < 0.01). Receiver operating characteristic curve (ROC) analysis was used to evaluate the diagnostic accuracy of serum IL-1ß and TNF-α for IDH. The area under the curve of IL-1ß 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-1ß were still risk factors for IDH. CONCLUSION: Pro-inflammatory cytokines (TNF-α and IL-1ß) could be potential predictors for IDH.

Defining Shock and Preshock for Mortality Risk Stratification in Cardiac Intensive Care Unit Patients.

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.

Kinetic Changes of Plasma Renin Concentrations Predict Acute Kidney Injury in Cardiac Surgery Patients.

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.

Altered Cardiovascular Defense to Hypotensive Stress in the Chronically Hypoxic Fetus.

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 α1-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.

Relative Change of Protidemia Level Predicts Intradialytic Hypotension.

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.

Point-of-care blood analysis of hypotensive patients in the emergency department.

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.

Fatty Acid-Saturated Albumin Reduces High Mortality and Fluid Requirements in a Rat Model of Hemorrhagic Shock Plus Tourniquet and Hypotensive Resuscitation.

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.

Hypotension and Hypocapnia During General Anesthesia in Piglets: Study of S100b as an Acute Biomarker for Cerebral Tissue Injury.

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.

A Prospective, Randomized, Double-Blinded Study of the Effect of Intravenous Ondansetron on the Effective Dose in 50% of Subjects of Prophylactic Phenylephrine Infusions for Preventing Spinal Anesthesia-Induced Hypotension During Cesarean Delivery.

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.

Development of a severe mesenteric traction syndrome during major abdominal surgery is associated with increased postoperative morbidity: Secondary data analysis on prospective cohorts.

PURPOSE: MTS is elicited during open abdominal surgery and is characterized by facial flushing, hypotension, and tachycardia in response to the release of prostacyclin (PGI2) 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-PGF1α, a stable metabolite of PGI2, 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.

Prevention of Intradialytic Hypotension with Intermittent Back-Filtrate Infusion Haemodiafiltration: Insights into the Underlying Mechanism.

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.

Relationship between Dose of Bolus Dialysate Infusion and Blood Pressure in Intermittent Infusion Hemodiafiltration.

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.

Maternal hyperuricemia as a marker of post-spinal hypotension and uterine tone during cesarean delivery: a prospective observational study.

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.