Regional cerebral oxygen saturation during cardiopulmonary resuscitation as a predictor of return of spontaneous circulation and favourable neurological outcome - A review of the current literature.

INTRODUCTION: Regional cerebral oxygen saturation (rSO2) can be measured non-invasively even at no- or low-flow states. It thus allows assessment of brain oxygenation during CPR. Certain rSO2 values had been associated with return of spontaneous circulation (ROSC) and neurological outcome in the past. Clear-cut thresholds for the prediction of beneficial outcome, however, are still lacking. METHODS: We conducted a database search to extract all available investigations on rSO2 measurement during CPR. Mean, median, and ΔrSO2 values were either taken from the studies or calculated. Thresholds for the outcome "ROSC" and "neurological outcome" were sought. RESULTS: We retrieved 26 publications for the final review. The averaged mean rSO2 for patients achieving ROSC was 41 ±â€¯12% vs. 30 ±â€¯12% for non-ROSC (p = .009). ROSC was not observed when mean rSO2 remained <26%. In ROSC patients, ΔrSO2 was 22 ±â€¯16% vs. 7 ±â€¯10% in non-ROSC patients (p = .009). A rSO2 threshold of 36% predicted ROSC with a sensitivity of 67% and specificity of 69% while ΔrSO2 of 7% showed a sensitivity of 100% and a specificity of 86% (AUC = 0.733 and 0.893, respectively). Mean rSO2 of 47 ±â€¯11% was associated with favourable and 38 ±â€¯12% with poor neurological outcome. There was, however, a great overlap between groups due to scarce data. CONCLUSION: Higher rSO2 consistently correlated with increased rates of ROSC. The discriminatory power of rSO2 to prognosticate favourable neurological outcome remains unclear. Measuring rSO2 during CPR could potentially facilitate clinical decision-making.

A pilot study on reparixin, a CXCR1/2 antagonist, to assess safety and efficacy in attenuating ischaemia-reperfusion injury and inflammation after on-pump coronary artery bypass graft surgery.

Reparixin, a CXCR 1/2 antagonist, has been shown to mitigate ischaemia-reperfusion injury (IRI) in various organ systems in animals, but data in humans are scarce. The aim of this double-blinded, placebo-controlled pilot study was to evaluate the safety and efficacy of reparixin to suppress IRI and inflammation in patients undergoing on-pump coronary artery bypass grafting (CABG). Patients received either reparixin or placebo (n = 16 in each group) after induction of anaesthesia until 8 h after cardiopulmonary bypass (CPB). We compared markers of systemic and pulmonary inflammation, surrogates of myocardial IRI and clinical outcomes using Mann-Whitney U- and Fisher's exact tests. Thirty- and 90-day mortality was 0% in both groups. No side effects were observed in the treatment group. Surgical revision, pleural and pericardial effusion, infection and atrial fibrillation rates were not different between groups. Reparixin significantly reduced the proportion of neutrophil granulocytes in blood at the beginning [49%, interquartile range (IQR) = 45-57 versus 58%, IQR = 53-66, P = 0·035], end (71%, IQR = 67-76 versus 79%, IQR = 71-83, P = 0·023) and 1 h after CPB (73%, IQR = 71-75 versus 77%, IQR = 72-80, P = 0·035). Reparixin patients required a lesser positive fluid balance during surgery (2575 ml, IQR = 2027-3080 versus 3200 ml, IQR = 2928-3778, P = 0·029) and during ICU stay (2603 ml, IQR = 1023-4288 versus 4200 ml, IQR = 2313-8160, P = 0·021). Numerically, more control patients required noradrenaline ≥ 0·11 µg/kg/min (50 versus 19%, P = 0·063) and dobutamine (50 versus 25%, P = 0·14). Therefore, administration of reparixin in CABG patients appears to be feasible and safe. It concurrently attenuated postoperative granulocytosis in peripheral blood.

Comparison of the effects of albumin 5%, hydroxyethyl starch 130/0.4 6%, and Ringer's lactate on blood loss and coagulation after cardiac surgery.

BACKGROUND: Infusion of 5% human albumin (HA) and 6% hydroxyethyl starch 130/0.4 (HES) during cardiac surgery expand circulating volume to a greater extent than crystalloids and would be suitable for a restrictive fluid therapy regimen. However, HA and HES may affect blood coagulation and could contribute to increased transfusion requirements. METHODS: We randomly assigned 240 patients undergoing elective cardiac surgery to receive up to 50 ml kg(-1) day(-1) of either HA, HES, or Ringer's lactate (RL) as the main infusion fluid perioperatively. Study solutions were supplied in identical bottles dressed in opaque covers. The primary outcome was chest tube drainage over 24 h. Blood transfusions, thromboelastometry variables, perioperative fluid balance, renal function, mortality, intensive care unit, and hospital stay were also assessed. RESULTS: The median cumulative blood loss was not different between the groups (HA: 835, HES: 700, and RL: 670 ml). However, 35% of RL patients required blood products, compared with 62% (HA) and 64% (HES group; P=0.0003). Significantly, more study solution had to be administered in the RL group compared with the colloid groups. Total perioperative fluid balance was least positive in the HA group [6.2 (2.5) litre] compared with the HES [7.4 (3.0) litre] and RL [8.3 (2.8) litre] groups (P<0.0001). Both colloids affected clot formation and clot strength and caused slight increases in serum creatinine. CONCLUSIONS: Despite equal blood loss from chest drains, both colloids interfered with blood coagulation and produced greater haemodilution, which was associated with more transfusion of blood products compared with crystalloid use only.

Ventilation during cardiopulmonary bypass: impact on heat shock protein release.

AIM: Cardiopulmonary bypass (CPB), utilized in on-pump coronary artery bypass graft procedures (CABG) induces generalized immune suppression, release of heat shock proteins (HSP), inflammatory markers and apoptosis-specific proteins. We hypothesized that continued mechanical ventilation during cardiopulmonary bypass attenuates immune response and HSP liberation. METHODS: Thirty patients undergoing conventional coronary artery bypass graft (CABG) operation were randomized into a ventilated on CPB (VG; N.=15) and a non-ventilated CPB group (NVG; N.=15). Blood samples were drawn at the beginning and end of surgery, as well as on the five consecutive postoperative days (POD). Molecular markers were measured by ELISA. Data are given as mean ± (SD). Mann-Whitney-U-test was used for statistical analysis. RESULTS: Serum concentrations of HSP70 were significantly lower in VG compared to NVG on POD-1 (VG: 1629±608 vs. NVG: 5203±2128.6 pg/mL, P<0.001). HSP27 and HSP60 depicted a minor increase in both study groups at the end of surgery without any intergroup differences (HSP27: VG 6207.9±1252.5 vs. NVG 7424.1±2632.5; HSP60: VG 1046.2±478.8 vs. NVG 1223.5±510.1). IL-8 and CK-18 M30 evidenced the highest serum concentrations at the end of surgery (IL-8: VG 119.5±77.9 vs. NVG 148.0±184.55; CK-18 M30: VG 62.1±39.2 vs. NVG 67.5±33.9) with no differences between groups. Decreased ICAM-1 serum concentrations were detected postoperatively, however ICAM-1 concentrations on POD-1 to POD-5 showed slightly elevated concentrations in both study groups with no intergroup differences. CONCLUSION: Significantly less HSP70 was detectable in patients receiving uninterrupted mechanical lung ventilation on CPB, indicating either different inflammatory response, cellular stress or cell damage between the ventilated and non-ventilated group. These data suggest that continued mechanical ventilation has a modulatory effect on the immune response in patients after CABG surgery.

Direct mapping of nuclear shell effects in the heaviest elements.

Quantum-mechanical shell effects are expected to strongly enhance nuclear binding on an "island of stability" of superheavy elements. The predicted center at proton number Z = 114, 120, or 126 and neutron number N = 184 has been substantiated by the recent synthesis of new elements up to Z = 118. However, the location of the center and the extension of the island of stability remain vague. High-precision mass spectrometry allows the direct measurement of nuclear binding energies and thus the determination of the strength of shell effects. Here, we present such measurements for nobelium and lawrencium isotopes, which also pin down the deformed shell gap at N = 152.

Influenza A-induced cardiogenic shock requiring temporary ECMO support and urgent heart transplantation.

We report a case of a child with familial cardiomyopathy who contracted H1N1 influenza followed by cardiovascular collapse requiring immediate arteriovenous ECMO support. Despite the lack of experience with heart transplantation (HTx) soon after H1N1 infection, HTx was considered as an exit strategy since restoration of cardiac function was considered unlikely. In contrast to the most common indication for ECMO use in patients with H1N1 infection, early ECMO support in cases with infection-induced myocardial decompensation may be lifesaving. Additionally, this report shows that urgent heart transplantation in a patient on ECMO support can be performed safely after recent H1N1 infection and simultaneous heparin-induced thrombocytopenia, which has not been reported before. This case also indicates that H1N1 vaccination should be considered for potential transplantation candidates to prevent severe infection.

Validation of cardiac output measurement with the LiDCO™ pulse contour system in patients with impaired left ventricular function after cardiac surgery.

After cardiac surgery, patients with low left ventricular ejection fraction probably benefit the most from accurate monitoring of continuous cardiac output. Thirty patients with impaired ventricular function were studied, and intermittent bolus thermodilution and continuous pulse contour (LiDCO plus™) cardiac output compared. Following lithium dilution calibration, a total of 220 paired results were recorded. Thermodilution and LiDCO measurements ranged from 2.3 to 11.0 and 2.6 to 10.8 l.min(-1), respectively. Corresponding means (SD) were 6.1 (1.6) and 6.2 (1.9) l.min(-1), with coefficients of variance of 26 and 31%, respectively. The correlation coefficient was 0.82, bias 0.28 l.min(-1) with upper and lower limits of agreement 1.96 and -1.41 l.min(-1); the percentage error was 27%. LiDCO showed good correlation, marginal bias and acceptable limits of agreement and percentage error. It could therefore potentially replace thermodilution as a means of measuring cardiac output in the ICU, particularly when determination of pulmonary artery pressure is not required.

Direct mass measurements above uranium bridge the gap to the island of stability.

The mass of an atom incorporates all its constituents and their interactions. The difference between the mass of an atom and the sum of its building blocks (the binding energy) is a manifestation of Einstein's famous relation E = mc(2). The binding energy determines the energy available for nuclear reactions and decays (and thus the creation of elements by stellar nucleosynthesis), and holds the key to the fundamental question of how heavy the elements can be. Superheavy elements have been observed in challenging production experiments, but our present knowledge of the binding energy of these nuclides is based only on the detection of their decay products. The reconstruction from extended decay chains introduces uncertainties that render the interpretation difficult. Here we report direct mass measurements of trans-uranium nuclides. Located at the farthest tip of the actinide species on the proton number-neutron number diagram, these nuclides represent the gateway to the predicted island of stability. In particular, we have determined the mass values of (252-254)No (atomic number 102) with the Penning trap mass spectrometer SHIPTRAP. The uncertainties are of the order of 10 keV/c(2) (representing a relative precision of 0.05 p.p.m.), despite minute production rates of less than one atom per second. Our experiments advance direct mass measurements by ten atomic numbers with no loss in accuracy, and provide reliable anchor points en route to the island of stability.

Alpha-Gal specific IgG immune response after implantation of bioprostheses.

BACKGROUND: We have previously shown that the alpha-Gal (Galalpha1.3-Galbeta1-4GlcNAc-R) epitope is a relevant xenoantigen present on bioprostheses utilized in cardiac surgery and elicits an alpha-Gal specific IgM immune response. We sought to investigate whether that immune response continues after valve implantation. MATERIALS AND METHODS: We collected plasma samples from patients who underwent bioprosthesis implantation (n = 19) or mechanical valve replacement (n = 8), respectively, prior to, at 10 days and at 3 months after cardiac surgery. ELISA was utilized to quantify alpha-Gal specific IgG and IgG subclasses. 3 bioprosthetic tissue samples were obtained from patients who had to undergo re-operation within 1 week (n = 1) or at 12-15 months (n = 2) after the initial operation. We utilized confocal laser scanning microscopy (CLSM) to detect the presence of alpha-Gal epitopes (IB4) and cell nuclei (DAPI). RESULTS: alpha-Gal specific IgG was significantly increased 3 months after implantation of bioprostheses compared to preoperative values (p < 0.001) and was significantly higher than alpha-Gal specific IgG levels of the control group (p < 0.05). IgG3 was the major subclass directed against alpha-Gal (p < 0.05, pre- vs. postoperative values). In CLSM analysis we demonstrated that bioprostheses explanted 1 week after implantation contained IB4/DAPI positive cells within the collagen matrix. In contrast, in patients who underwent reoperation after 12 months, porcine tissue showed a complete lack of IB4/DAPI. CONCLUSION: Our results indicate that the implantation of bioprostheses elicits a specific humoral immune response against alpha-Gal bearing cells compared to controls within 3 months after cardiac surgery. The complete absence of IB4/DAPI positive structures 12 months after implantation indicates a specific degradation of alpha-Gal bearing cells through previous exposure to the human blood circuit.

Secretion of soluble ST2 - possible explanation for systemic immunosuppression after heart surgery.

BACKGROUND: Cardiopulmonary bypass is known to affect cytokine release leading to a generalized endogenous immune reaction similar to that described in sepsis, without having been explored in great detail. Therefore we evaluated the anti- and pro-inflammatory cytokine responses after heart surgery. METHODS: 16 patients who underwent coronary artery bypass graft (CABG) surgery with extracorporeal circulation were included. ST2, IL-4 and IL-10 served as markers for TH2 cytokine response; IL-6, IL-8 and IFN-gamma as TH1 markers. Furthermore, total immunoglobulin subtype analysis (IgM, IgG, IgE) was performed. RESULTS: Serum levels of soluble ST2 started to climb at 60 minutes (from 38 +/- 14 preoperatively to 1 480 +/- 890 pg/ml) and peaked 24 hours after surgery (13 360 +/- 2 840 pg/ml, P < 0.001). IL-10 reached a maximum at 60 minutes and returned to baseline levels 24 hours later. IL-6 and IL-8 levels peaked 60 minutes after surgery. IL-4 and IFN-gamma did not change. Only IgM showed a significant peak on day eight ( P < 0.001). CONCLUSION: Our results demonstrate that CABG surgery induces a massive long-lasting secretion of ST2, a protein related to immune suppression.

Restoration of the n=82 shell gap from direct mass measurements of 132,134Sn.

A high-precision direct Penning trap mass measurement has revealed a 0.5-MeV deviation of the binding energy of (134)Sn from the currently accepted value. The corrected mass assignment of this neutron-rich nuclide restores the neutron-shell gap at N=82, previously considered to be a case of "shell quenching." In fact, the new shell gap value for the short-lived (132)Sn is larger than that of the doubly magic (48)Ca which is stable. The N=82 shell gap has considerable impact on fission recycling during the r process. More generally, the new finding has important consequences for microscopic mean-field theories which systematically deviate from the measured binding energies of closed-shell nuclides.

Mass measurements beyond the major r-process waiting point 80Zn.

High-precision mass measurements on neutron-rich zinc isotopes (71m,72-81)Zn have been performed with the Penning trap mass spectrometer ISOLTRAP. For the first time, the mass of 81Zn has been experimentally determined. This makes 80Zn the first of the few major waiting points along the path of the astrophysical rapid neutron-capture process where neutron-separation energy and neutron-capture Q-value are determined experimentally. The astrophysical conditions required for this waiting point and its associated abundance signatures to occur in r-process models can now be mapped precisely. The measurements also confirm the robustness of the N=50 shell closure for Z=30.

Low-dose remifentanil to suppress haemodynamic responses to noxious stimuli in cardiac surgery: a dose-finding study.

BACKGROUND: High-dose remifentanil (1-5 microg kg-1 min-1), commonly used for cardiac surgery, has been associated with muscle rigidity, hypotension, bradycardia, and reduced cardiac output. The aim of this study was to determine an optimal lower remifentanil dose, which should be accompanied by fewer adverse events, that still effectively suppresses haemodynamic responses to typical stressful stimuli (i.e. intubation, skin incision, and sternotomy). METHODS: Total i.v. anaesthesia consisted of a target-controlled propofol (2 microg ml-1) and a remifentanil infusion. Forty patients were allocated to receive either a constant infusion of remifentanil at 0.1 microg kg-1 min-1 or up-titrations to 0.2, 0.3, or 0.4 microg kg-1 min-1, respectively, 5 min before each stimulus. Subsequently, changes in heart rate and mean arterial blood pressure were recorded for 8 min. Increases exceeding 20% of baseline were considered to be of clinical relevance. Patients who exhibited these alterations were termed responders. RESULTS: The number of responders was less with the two higher remifentanil dosages (P<0.05) while propofol target doses could either be kept at the same level or even be reduced without affecting the plane of anaesthesia. Although single phenylephrine bolus had to be applied more frequently in these two groups (P<0.05), no severe haemodynamic depression was observed. CONCLUSIONS: Remifentanil at 0.3 and 0.4 microg kg-1 min-1 in combination with a target-controlled propofol infusion in the pre-bypass period is well tolerated. It appears to mitigate potentially hazardous haemodynamic responses from stressful stimuli equally well as higher doses when compared with data from the literature.

Magnesium moderately decreases remifentanil dosage required for pain management after cardiac surgery.

BACKGROUND: Magnesium is a calcium and an NMDA-receptor antagonist and can modify important mechanisms of nociception. We evaluated the co-analgesic effect of magnesium in the postoperative setting after on-pump cardiac surgery. METHODS: Forty patients randomly received either magnesium gluconate as an i.v. bolus of 0.21 mmol kg(-1) (86.5 mg kg(-1)) followed by a continuous infusion of 0.03 mmol(-1) kg(-1) h(-1) (13.8 mg kg(-1) h(-1)) or placebo for 12 h after tracheal extubation. After surgery, remifentanil was decreased to 0.05 microg kg(-1) min(-1) and titrated according to a pain intensity score (PIS, range 1-6) in the intubated, awake patient and a VAS scale (range 1-100) after extubation. If PIS was > or =3 or VAS > or =30, the infusion was increased by 0.01 microg kg(-1) min(-1); if ventilatory frequency was < or =10 min(-1) it was decreased by the same magnitude. RESULTS: Magnesium lowered the cumulative remifentanil requirement after surgery (P<0.05). PIS > or =3 was more frequent in the placebo group (P<0.05). Despite increased remifentanil demand, VAS scores were also higher in the placebo group at 8 (2 vs 8) and 9 h after extubation (2 vs 7) (P<0.05). Dose reductions attributable to a ventilatory frequency < or =10 min(-1) occurred more often in the magnesium group (17 vs 6; P<0.05). However, time to tracheal extubation was not prolonged. CONCLUSIONS: Magnesium gluconate moderately reduced the remifentanil consumption without serious side-effects. The opioid-sparing effect of magnesium may be greater at higher pain intensities and with increased dosages.

Isoflurane applied during ischemia enhances intracellular calcium accumulation in ventricular myocytes in part by reactive oxygen species.

BACKGROUND: Isoflurane applied before myocardial ischemia has a beneficial preconditioning effect which involves generation of reactive oxygen species (ROS); ROS, however, have been implicated in critical cytosolic calcium ([Ca2+]i) overload during ischemia. We therefore investigated isoflurane's effects on intracellular Ca2+ handling in ischemic ventricular myocytes and the association with ROS. METHODS: Simulated ischemia was induced in electrically stimulated rat ventricular myocytes for 30 min (ischemia). Isoflurane-treated cells were additionally exposed to 1MAC of isoflurane (ischemia + iso). To determine the contribution of ROS to Ca2+ homeostasis during ischemia in both groups, the intracellular ROS scavenger, N-mercaptopropionylglycine (MPG), was added to the superfusion buffer. The fluorescent ratiometric Ca2+ dye fura-2 was employed to determine [Ca2+]i. RESULTS: Resting and peak [Ca2+]i increased in the ischemia and the ischemia + iso group. However, Ca2+ accumulation was most prominent in isoflurane-treated cardiomyocytes (P < 0.05) and could be mitigated by MPG in both groups (P < 0.001). Isoflurane also decreased the rate constant of the Ca2+ transient decline but did not further diminish the amplitude of the transient during ischemia. CONCLUSION: Isoflurane when applied during ischemia appears to worsen [Ca2+]i overload, which is caused by impeding Ca2+ clearance. As MPG mitigated the increase in [Ca2+]i, isoflurane seems to enhance ROS-mediated effects on intracellular Ca2+ handling in cellular ischemia.

Perfusion temperature during cardiopulmonary bypass does not affect serum S-100beta release.

BACKGROUND: The potentially harmful effects of normothermia on neurological outcome during cardiopulmonary bypass (CPB) are controversial. METHODS: In this study, we compared the early and late release patterns of S-100beta, a marker of cerebral injury, after normothermic and moderately hypothermic CPB. Forty-eight patients undergoing coronary artery bypass grafting were randomly assigned to either the normothermia (37 degrees C) or the hypothermia (32 degrees C) group. Serum S-100beta levels were measured until 24 h after CPB. Neurological examination was performed before and after surgery. RESULTS: With the exception of intraoperative blood glucose levels, there were no differences between groups. This also applied to peak S-100beta values (Gr-N: 3.5 +/- 1.9 microg/l; Gr-H: 3.5 +/- 3.4 microg/l) and values after 24 h (Gr-N: 0.32 +/- 0.16 microg/l; Gr-H: 0.35 +/- 0.28 microg/l). CONCLUSIONS: The similar pattern of S-100beta release without evident neurological complications in the normothermia group does not suggest an increase in cerebral injury during normothermic CPB.