Search

Background and Purpose— Although conceivably relevant for penumbra oxygenation, the optimal levels of hemoglobin (Hb) and hematocrit (Hct) in patients with acute ischemic stroke are unknown. Methods— We identified patients from our prospective local stroke database who received intravenous thrombolysis based on multimodal magnet resonance imaging during the years 1998 to 2009. A favorable outcome at 3 months was defined as a modified Rankin Scale score ≤2 and a poor outcome as a modified Rankin Scale score ≥3. The dynamics of Hemoglobin (Hb), Hematocrit (Hct), and other relevant laboratory parameters as well as cardiovascular risk factors were retrospectively assessed and analyzed between these 2 groups. Results— Of 217 patients, 114 had a favorable and 103 a poor outcome. In a multivariable regression model, anemia until day 5 after admission (odds ratio [OR]=2.61; 95% CI, 1.33 to 5.11; P =0.005), Hb nadir (OR=0.81; 95% CI, 0.67 to 0.99; P =0.038), and Hct nadir (OR=0.93; 95% CI, 0.87 to 0.99; P =0.038) remained independent predictors for poor outcome at 3 months. Mortality after 3 months was independently associated with Hb nadir (OR=0.80; 95% CI, 0.65 to 0.98; P =0.028) and Hb decrease (OR=1.34; 95% CI, 1.01 to 1.76; P =0.04) as well as Hct decrease (OR=1.12; 95% CI, 1.01 to 1.23; P =0.027). Conclusions— Poor outcome and mortality after ischemic stroke are strongly associated with low and further decreasing Hb and Hct levels. This decrease of Hb and Hct levels after admission might be more relevant and accessible to treatment than are baseline levels.

Purpose Prognosis of patients with glioblastoma is poor. Therefore, in glioblastoma patients, we analyzed whether antitumor vaccination with a virus-modified autologous tumor cell vaccine is feasible and safe. Also, we determined the influence on progression-free survival and overall survival and on vaccination-induced antitumor reactivity. Patients and Methods In a nonrandomized study, 23 patients were vaccinated and compared with nonvaccinated controls (n = 87). Vaccine was prepared from patient's tumor cell cultures by infection of the cells with Newcastle Disease Virus, followed by gamma-irradiation, and applied up to eight times. Antitumor immune reactivity was determined in skin, blood, and relapsed tumor by delayed-type hypersensitivity skin reaction, ELISPOT assay, and immunohistochemistry, respectively. Results Establishment of tumor cell cultures was successful in approximately 90% of patients. After vaccination, we observed no severe side effects. The median progression-free survival of vaccinated patients was 40 weeks (v 26 weeks in controls; log-rank test, P = .024), and the median overall survival of vaccinated patients was 100 weeks (v 49 weeks in controls; log-rank test, P < .001). Forty-five percent of the controls survived 1 year, 11% survived 2 years, and there were no long-term survivors (≥ 3 years). Ninety-one percent of vaccinated patients survived 1 year, 39% survived 2 years, and 4% were long-term survivors. In the vaccinated group, immune monitoring revealed significant increases of delayed-type hypersensitivity reactivity, numbers of tumor-reactive memory T cells, and numbers of CD8+ tumor-infiltrating T-lymphocytes in secondary tumors. Conclusion Postoperative vaccination with virus-modified autologous tumor cells seems to be feasible and safe and to improve the prognosis of patients with glioblastomas. This could be substantiated by the observed antitumor immune response.

In 25 cardiac surgical patients, right ventricular ejection fraction was continuously measured with a new pulmonary artery catheter and transoesophageal echocardiography, scanning the 'fractional area change' in a standardised transatrial cross section area. Measurements were recorded at three predefined time points (pre-, intra-, and postoperatively). Both methods were compared using the Bland-Altman analysis. Comparing right ventricular ejection fraction values obtained from the pulmonary artery catheter with those assessed by transoesophageal echocardiography, bias was -3.7%, with a precision of 30.9%. Bias and precision significantly improved when the heart rate was less than 100 beats.min(-1), pulmonary artery pressures were low and cardiac performance adequate. In conclusion, the new continuous pulmonary artery catheter system appears to be a valid and useful bedside monitoring device in the haemodynamic management of critically ill patients.

Although several clinical studies have shown that increased serum concentrations of protein S100B predict ischaemic brain damage after cardiac surgery, S100B may also be released from the heart or other injured tissue. We therefore investigated the correlation between serum S100B levels and those of the specific cardiac marker troponin I in order to assess the cerebral vs. extracerebral origin of S100B. In 64 cardiac surgical patients, serial blood samples were drawn for the measurement of S100B and troponin I before surgery and for seven days after surgery. Neurological function was assessed before with the National Institutes of Health Stroke Scale and the Folstein Mini Mental Test. The data show that a sustained increase in serum S100B levels is associated with neurological dysfunction, as witnessed by a positive correlation between S100B values and the results of the neuropsychological tests. In contrast, the early postoperative increased levels of protein S100B derive from cardiac tissue, as shown by the positive correlation between S100B and cardiac troponin I levels.

Inhibition of angiogenesis by blocking angiogenic cytokines or their pathways has become a major target in experimental cancer therapies. This therapeutical approach requires a profound knowledge of growth factor profiles that contribute to tumor growth and progression. The respective knowledge is presently rather incomplete for head and neck squamous cell carcinomas (HNSCC). Therefore we studied expression of several angiogenic cytokines including VEGF, bFGF, PDGF-AB, PDGF-BB, G-CSF and GM-CSF in HNSCC in vivo and in vitro. In tumor tissues expression of all cytokines was observed albeit with marked differences concerning intensity and distribution pattern. Quantification of the cytokines in the supernatant of 15 tissue-corresponding HNSCC cultures revealed that VEGF, PDGF-AB and less frequently GM-CSF were secreted in high amounts of up to 13 ng/ml/10(6) cells. Twenty percent of the HNSCC cultures expressed only 1 cytokine in biologically active amounts, 60% 2 or 3 and 20% expressed the maximum of 4 cytokines simultaneously. Interestingly, we observed a distinct cytokine pattern: HNSCC cells secreting only 1 or 2 cytokines presented always with either VEGF and/or PDGF-AB, while G-CSF and GM-CSF were secreted primarily together with VEGF and PDGF-AB. The number of cytokines expressed by HNSCC cells correlated with the microvessel density of the original tumor and with the clinical outcome: tumors producing at least 3 cytokines revealed a significantly poorer patient prognosis. Our data indicate a major role for VEGF and PDGF-AB in HNSCC and that the additional secretion of G-CSF or GM-CSF might contribute to a poorer prognosis in patients suffering from these tumors.

Objective: The aim of the present study was to evaluate the correlation, accuracy, and precision of transpulmonary thermodilution cardiac output (CO) measurement. For this purpose, this technique was compared with the clinical gold standard, the CO measurement by pulmonary artery catheter in patients after coronary artery bypass grafting (CABG). Design: A prospective clinical study. Setting: A university medical center. Participants: Seventy-five patients in an intensive care unit (ICU) after CABG. Interventions: Standard (SCO) and transpulmonary thermodilution CO measurement (TPCO) measurements were simultaneously performed in triplicate by central venous injection of cooled saline solution. All variables were recorded at five different time points of measurement during weaning from mechanical ventilation. Measurements and Main Results: CO measurements yielded 375 data pairs. SCO ranged from 2.0 to 10.2 L/min, and TPCO from 1.3 to 10.6 L/min. During the entire observation period, TPCO measurements tended to yield relatively high values, whereas SCO measurements resulted in lower values. Correlation between TPCO and SCO measurements was significant (r = 0.73; p < 0.05), accompanied by an accuracy with a bias of 0.456 L/min (7.3%) and a precision of 1.156 L/min (18.5%). Conclusion: In most patients, TPCO measurement will not replace the conventional technique by pulmonary artery catheter, but in some patients it offers an attractive, reliable, and safe method to determine CO.

We evaluated intermittent and continuous thermodilution cardiac output data in 12 patients undergoing orthotopic liver transplantation. Measurements were performed at 16 predefined time points between induction of anaesthesia and 3 h after reperfusion of the liver graft. Cardiac output measurements yielded 192 data pairs (intermittent cardiac output range: 1.8-18.9 l.min-1, continuous cardiac output range: 3.3-20.0 l.min-1). During most of the procedure the correlation between intermittent and continuous cardiac output measurements was significant (r = 0.87, p0.0001), accompanied with a bias of -0.240 l.min-1 and a degree of precision of 1.789 l.min-1 (10.0 l.min-1:1.137 l.min-1,or = 10.0 l.min-1:2.220 l.min-1). However, in the early phases after caval clamping and after reperfusion, accuracy was not acceptable. Only during these phases did the difference between the mean values of pulmonary artery blood temperature and rectal temperature increase (after caval clamping) or decrease (after reperfusion). In conclusion, despite acceptable levels of accuracy and precision between intermittent and continuous cardiac output measurement under stable conditions, both methods showed markedly decreased accuracy and precision in the early phases after caval clamping and after reperfusion, possibly owing to increased thermal noise.

Purpose: Although it is known that weaning from mechanical ventilation is associated with alterations in intrathoracic pressure, lung volume, and venous return, changes in intrathoracic fluid volumes during weaning are not reported. Especially in patients with impaired cardiac function, the development of pulmonary edema during weaning has been described. Thus, we investigated changes in intrathoracic fluid volumes in patients after coronary artery bypass grafting after changing the ventilatory pattern from mechanical to spontaneous ventilation. Materials and methods: Intrathoracic blood volume index (ITBVI), pulmonary blood volume index (PBVI), and extravascular lung water (EVLW) were calculated during mechanical ventilation (T1), Tpiece breathing (T2), and spontaneous breathing after extubation of the trachea (T3) in 72 consecutive patients after coronary artery bypass grafting using a combined dye-thermal dilution method. Results: Changing from mechanical ventilation to T-piece breathing resulted in an increase in ITBVI from 880 ± 22 mL/m2 to 970 ± 22 mL/m2 (P < .01), and in PBVI from 162 ± 6 mL/m2 to 173 ± 6 mL/m2 (P < .01). After extubation of the trachea, both parameters decreased again (ITBVI, 879 ± 20 mL/m2; PBVI, 160 ± 7 mL/m2). EVLW remained unchanged after transition to T-piece breathing (T1, 5.8 ± 0.3 mL/kg; T2, 6.0 ± 0.3 mL/kg), but increased to 6.6 ± 0.5 mL/kg (P < .01) after extubation of the trachea. However, pathological values of EVLW were not observed. Conclusions: In patients after coronary artery bypass grafting, changes in intrathoracic intravascular fluid volumes during weaning are restricted to the period of T-piece breathing and reflect an increased venous return. The maintenance of EVLW in the normal range during weaning indicates that cardiac function was matched to this elevated preload.

The aim of this study was to investigate the influence of the platelet-activating factor (PAF) antagonist BN52021 on endotoxin-induced leukocyte-endothelium interactions and on venular microcirculation. The rates of leukocyte adherence and changes in red cell velocity, volumetric blood flow, vessel diameter, and venular shear rate were monitored in rat mesenteric venules following intravenous lipopolysaccharide (LPS) exposure (15 mg/kg body wt). The experiments were performed in LPS-treated control animals and in animals pretreated with the PAF receptor antagonist BN52021. LPS exposure induced a marked increase in adherent leukocytes in the control group compared to the BN52021-pretreated group. Thirty minutes after LPS injection, 6.1 +/- 0.8 leukocytes were adherent to 100 microns of venule in the control group compared to 2.5 +/- 0.5 in BN52021-pretreated animals (P0.01). The increased leukocyte adherence in the control group was accompanied by leukocytopenia. Red cell velocity, volumetric blood flow, vessel diameter, and venular shear rate did not differ between groups, indicating that increased leukocyte adherence in the control group was not due to diminished hydrodynamic dispersal forces. The attenuation of leukocyte adherence by the PAF receptor antagonist BN52021 suggests that PAF is involved in the mediation of the initial process of leukocyte sticking to the endothelium after LPS stimulation.

OBJECTIVES To determine the influence of ketamine on endotoxin-induced leukocyte adherence and venular microhemodynamics. DESIGN Randomized, controlled trial. SETTING Experimental laboratory. SUBJECTS Thirty male Wistar rats. INTERVENTIONS The rats were pretreated with ketamine (10 mg/kg iv) or 0.9% saline, and both groups were given endotoxin (Escherichia coli lipopolysaccharide; 5 mg/kg iv). The control group received two doses of 0.9% saline. MEASUREMENTS AND MAIN RESULTS The rates of leukocyte adherence and changes in microhemodynamics were monitored in rat mesenteric venules, using in vivo video microscopy. The number of adherent leukocytes was determined on-line in 10-min intervals from 60 mins before until 2 hrs after endotoxin administration. Venular diameters, red blood cell velocity, volumetric blood flow, and the venular wall shear rate were monitored before and at 10, 30, and 60 mins after endotoxin exposure. A 6.3-fold increase in the number of adherent leukocytes was observed 10 mins after administration of endotoxin when compared with control animals (5.87 +/- 0.69 vs. 0.93 +/- 0.21 adherent cells/100 microns; p < .001). This increase remained unchanged for 120 mins. In ketamine-pretreated rats, a 2.6-fold increase in leukocyte adherence occurred during the first 20 mins after endotoxin exposure (2.40 +/- 0.46 vs. 0.93 +/- 0.21 adherent cells/100 microns; p < .01). However, no difference in the number of adherent leukocytes between ketamine-pretreated and control animals was found after this 20-min period. In animals of the control group, no increase in leukocyte adherence occurred during the entire observation time. Diameters of mesenteric venules did not change after endotoxin exposure in any of the groups. Red blood cell velocity and venular blood flow in the endotoxin-treated groups decreased 10 mins after the injection of endotoxin when compared with controls, but these values did not show any difference when they were compared between ketamine and saline-pretreated animals. Similarly, venular wall shear rate in the endotoxin-treated groups decreased 10 and 30 mins after injection of endotoxin. However, no significant difference occurred between ketamine and saline-pretreated animals. CONCLUSIONS Pretreatment with ketamine attenuates endotoxin-induced leukocyte adherence by a shear rate-independent mechanism, suggesting reduced expression of adhesion molecules. These results indicate that ketamine exerts an anti-inflammatory effect, which might be beneficial in septic patients.

Summary Background During cardiopulmonary resuscitation (CPR), thrombolysis can help to stabilise patients with pulmonary embolism and myocardial infarction. Moreover, thrombolysis during CPR has beneficial effects on cerebral reperfusion after cardiac arrest. We investigated this new therapeutic approach in patients in whom conventional CPR had been unsuccessful. Methods We assessed, in a prospective study, patients undergoing CPR after out-of-hospital cardiac arrest for cardiological reasons in whom return of spontaneous circulation was not achieved within 15 min. According to the Ustein criteria, our control group consisted of patients who were assessed during 1 year. After this year patients were treated with a bolus of 5000 U of heparin and 50mg, over 2 min, of tissue-type plasminogen activator (rt-PA treated group). This intervention was repeated if return of spontaneous circulation was not achieved within the following 30 min. For controls only CPR was given. Findings Overall, 90 patients were included; heparin and rt-PA were given to 40 patients. There were no bleeding complications related to the CPR procedures. Of the rt-PA group, 68% (27) had return of spontaneous circulation and 58% (23) were admitted to a cardiac intensive care unit, compared with 44% (22; p=0·026) and 30% (15; p=0·009) of the controls, respectively. At 24 h after cardiac arrest a larger proportion of the rt-PA group than of the controls was alive (35% [14] vs 22% [11], p=0·171), and 15% (six) of rt-PA-treated patients and 8% (four) of controls could be discharged from hospital. Interpretation After initially unsuccessful out-of-hospital CPR, thrombolytic therapy combined with heparin is safe and might improve patient outcome. On the basis of our data a randomised controlled trial might be regarded as ethical.

Background —The results of early conventional tests do not correlate with cerebral outcome after cardiac arrest. We investigated the serum levels of astroglial protein S-100 as an early marker of brain damage and outcome after cardiac arrest. Methods and Results —In 66 patients undergoing cardiopulmonary resuscitation after nontraumatic cardiac arrest, blood samples for the evaluation of S-100 were drawn immediately after and 15, 30, 45, and 60 minutes; 2, 8, 24, 48, and 72 hours; and 7 days after initiation of cardiopulmonary resuscitation. Moreover, the serum levels of neuron-specific enolase were determined between 2 hours and 7 days. If patients survived for >48 hours, brain damage was assessed by a combination of neurological, cranial CT, and electrophysiological examinations. Overall, 343 blood samples were taken for the determination of S-100. Maximum S-100 levels within 2 hours after cardiac arrest were significantly higher in patients with documented brain damage (survivors and nonsurvivors, 3.70±0.77 μg/L) than in patients without brain damage (0.90±0.29 μg/L). Significant differences between these 2 groups were observed from 30 minutes until 7 days after cardiac arrest. In addition, the positive predictive value of the S-100 test at 24 hours for fatal outcome within 14 days was 87%, and the negative predictive value was 100% ( P Conclusions —Astroglial protein S-100 is an early and sensitive marker of hypoxic brain damage and short-term outcome after cardiac arrest in humans.

Objective: To determine sex hormone-binding globulin (SHBG) and osteocalcin (OC) levels in patients undergoing coronary artery bypass graft surgery to clarify the status of peripheral thyroid metabolism and to correlate SHBG and OC with thyroid hormones and adverse postoperative events. Design: Prospective study. Setting: University medical center. Participants: Fifty randomly selected patients undergoing coronary artery bypass graft surgery. Interventions: On the morning of surgery before induction of anesthesia; 30 minutes after cross-clamping of the aorta; 2 hours and 6 hours after aortic cross-clamp removal; and on the first, second, third, and seventh postoperative mornings, blood samples were drawn and analyzed for OC, SHBG, triiodothyronine (tT3), free T3 (fT3), thyroxine (tT4), free T4 (fT4), thyroid-stimulating hormone, and thyroid-binding globulin. Adverse postoperative events were recorded. Measurements and Main Results: Mean tT3 and fT3 decreased on average by 35% and 18% but remained within the normal range perioperatively. Similarly, mean SHBG and OC remained within the normal range. More than half of the patients investigated (60%) had OC concentrations below the normal range. Patients with pathologically decreased tT3 (n = 6) and tT4 (n = 16) intraoperatively and postoperatively had SHBG and OC concentrations similar to those in patients with normal tT3 and tT4 levels. Patients with postoperative complications had significantly lower OC levels preoperatively and on the first postoperative morning than those with an uneventful postoperative recovery. Conclusion: Despite significant intraoperative and postoperative decreases in levels of thyroid hormones, low T3 syndrome was rare in this patient population. Unchanged concentrations of SHBG and OC in patients with pathologically decreased tT3 or tT4 suggest normal local thyroid exposure at the tissue sites in these patients. OC may act as a predictor for postoperative outcome. Copyright © 2000 by W.B. Saunders Company

OBJECTIVE—To test the effect of a physician staffed advanced cardiac life support (ALS) system on patient outcome following out-of-hospital cardiac arrest. DESIGN—Observational study. SETTING—Two tier basic life support (BLS) and physician staffed ALS services in the midsized urban/suburban area of Heidelberg, Germany. PATIENTS—All patients suffering out-of-hospital cardiac arrest of cardiac aetiology between January 1992 and December 1994 and who were covered by ALS services. INTERVENTIONS—Physician staffed ALS services. MAIN OUTCOME MEASURES—Return of spontaneous circulation, hospital discharge, and one year survival, according to the Utstein style. RESULTS—Of 330 000 inhabitants, 755 suffered from cardiac arrest covered by the Heidelberg ALS services. In 512 patients, cardiopulmonary resuscitation had been initiated. Of 338 patients with cardiac aetiology, return of spontaneous circulation was achieved in 164 patients (49%), 48 (14%) were discharged alive, and 40 (12%) were alive one year later; most of these patients showed good neurological outcome. Thus, 4.85 patients with cardiac aetiology were saved by the ALS services and discharged alive per 100 000 inhabitants a year. Ventricular fibrillation or tachycardia was detected in 106 patients (31%), other cardiac rhythms in 40 (12%), and asystole in 192 (57%). Hospital discharge rates (and one year survival) in these subgroups were 34.0% (29.2%), 12.5% (7.5%), and 3.6% (3.1%), respectively. Discharge rates increased if cardiac arrest was witnessed (bystander, 20.0%; BLS/ALS personnel, 21.4%; non-witnessed arrest, 3.3%; p 8 minutes, 8.1%; p

Background Endotoxin activates leukocyte-endothelial cell adhesion, vascular leakage, and changes in vascular micro-hemodynamics. The aim of this study was to determine whether lidocaine, which inhibits the activation of leukocytes, could attenuate microcirculatory disturbances during endotoxemia. Methods Thirty anesthetized male rats were randomly assigned to receive one of three treatments (n = 10 for each group): infusion of saline (control group), infusion of Escherichia coli endotoxin (LPS group: 2 mg x kg(-1) x h(-1) lipopolysaccharides) without lidocaine treatment, or infusion of endotoxin with lidocaine pretreatment 30 min before baseline measurements (lidocaine group: intravenous bolus of 2 mg/kg and continuous infusion of 2 mg x kg(-1) x h(-1)). Leukocyte adherence, erythrocyte velocity (V(RBC), and vessel diameters (Dv) were determined at baseline and at 60 and 120 min in mesenteric postcapillary venules using in vivo videomicroscopy. Macromolecular leakage was determined by measuring the extravasation of fluorescence-labeled albumin. Venular wall shear rate (tau) was calculated according to the equation tau = 8 x V(RBC) x Dv(-1). Results Lidocaine significantly attenuated the increase of leukocyte adherence during endotoxemia. There were no significant differences of tau within or between the groups. Macromolecular leakage exhibited the greatest increase in the LPS group. In the lidocaine group, it was significantly decreased but still increased compared with the control group. Conclusions These results show that lidocaine attenuates endotoxin-induced alterations in leukocyte-endothelial cell adhesion and macromolecular leakage, which suggests that lidocaine may have a therapeutic role in preventing endothelial damage in sepsis.