Pulmonary and circulatory parameter guided anesthesia in patients with ischemic stroke undergoing endovascular recanalization.

BACKGROUND AND PURPOSE: Endovascular recanalization in ischemic stroke is often performed under general anesthesia. Some studies have shown a detrimental effect of general anesthesia. The reasons are unknown. METHODS: This was an observational study with retrospective and prospective phases. From 2008 to 2010, 60 patients treated by endovascular recanalization due to proximal vessel occlusion were analyzed with regard to ventilation parameters, blood gas values, blood pressure, and clinical parameters (pre-protocol phase). Subsequently, a protocol with target values for end-tidal CO2 (Petco2) and systolic blood pressure (SBP) was introduced and prospectively analyzed in 64 patients in 2012 (protocol phase). RESULTS: In the pre-protocol phase, significant hypocapnia (<30 mm Hg), a decrease in SBP after intervention (p<0.001), and an increase in SBP after extubation (p<0.001) were observed. After implementing the protocol in 2012, 63% of Petco2 values and 55% of SBP values (median) of the duration of intervention were within the predefined range. Severe hypocapnia and hypotension (SBP <100 mm Hg) after the intervention were significantly reduced. Longer duration of Petco2 values within 40-45 mm Hg, intracerebral hemorrhage, longer door to needle time, older age, unsuccessful recanalization, longer duration of endovascular treatment, and higher cumulative dose of norepinephrine were associated with an unfavorable outcome (modified Rankin Scale score >2). Intracerebral hemorrhage (OR 0.028, p=0.001), age (OR 0.9, p=0.013), and cumulative dose of norepinephrine (OR 0.142, p=0.003) were independent predictors of an unfavorable outcome. CONCLUSIONS: In patients receiving endovascular stroke treatment under general anesthesia, the cumulative dose of norepinephrine was an independent predictor of an unfavorable outcome. Further studies are needed to evaluate the optimal management of blood pressure in these patients, and whether avoidance of catecholamines could partly explain the improved outcomes for patients treated under conscious sedation in retrospective studies.

VEGF: a surrogate marker for peripheral vascular disease.

This study aims to evaluate the value of VEGF as a surrogate marker for peripheral vascular disease (PVD). Prior to treatment, serum VEGF levels were evaluated by enzyme-linked immunosorbent assay (ELISA) in 293 PVD patients. Risk factors and clinical parameters of PVD were documented. Twenty-six age-matched healthy volunteers served as controls. Serum VEGF values strongly correlated with Fontaine stages (p<0.006, stage IV vs. controls). High VEGF values prior to treatment were associated with poor outcome. Serum VEGF appears to indicate the severity of PVD and might serve as a surrogate indicator of disease severity.

Contrast harmonic imaging ultrasound and perfusion imaging for surveillance after endovascular abdominal aneurysm repair regarding detection and characterization of suspected endoleaks.

OBJECTIVE: Is Contrast Harmonic Imaging (CHI) comparable to computed tomography angiography (CTA) scan in detecting and characterizing suspected endoleaks after endovascular abdominal aneurysm repair in a non-selected group including reintervention procedure and branched endografts in daily practice? MATERIAL/METHODS: In a prospective study computed tomography angiography (CTA) and contrast-enhanced ultrasound (CEUS) were performed in 30 consecutive patients (26 males, 4 females, mean age: 72 years, range: 38-87) with suspected endoleaks in follow-up (mean 13 months, range: 1-95) after endovascular abdominal aneurysm repair or procedure in dissection or penetrated ulcer of the aorta (25 infrarenal, 5 suprarenal stent grafts, mean aortic diameter 56 mm, range: 27-98). CTA was supposed to be gold standard for determining the presence of endoleaks (multislice CT, collimation 16 x 0.75 mm, 100 ml of iodized contrast agent bolus). Ultrasonography used a multi-frequency probe (1-4 MHz) with the modalities of colour coded Doppler sonography (CCDS), power Doppler (PD) combined with contrast enhancement and the technique of contrast harmonic imaging (CHI) and low mechanical index (MI < 0.2). 2.4 ml of SonoVue (Bracco, Altana Pharma GmbH, Italy) were administered to each patient intravenously as a bolus injection. RESULTS: Out of 30 patients, 21 endoleaks were identified in CTA (6 type I or III, 15 type II), 22 in CHI. Thus, sensitivity for CHI was therefore 99%, its specificity 85% (Spearman correlation coefficient (CC) 0.92). In follow-up the localizations of endoleak type I or III exclusively detected by CHI were confirmed as true positive by angiography. Due to its dynamic characteristic CHI seemed to be more helpful in characterization of endoleaks than CTA. In case of a rupture after reintervention a type III endoleak leads to prompt intervention before receiving the result of the CT scan. Altogether, CHI failed to identify 1 combined type I and II endoleak (sensitivity 0.99). Both, CCDS and PD were positive only in 6/30 patients (CC 0.33 and 0.39). Interestingly the application of contrast agent doubles the detection rate of endoleaks (12/30) in CCDS and PD (CC 0.39). CONCLUSION: Contrast harmonic imaging (CHI) compared to computed tomography angiography (CTA) accurately depicts endoleaks after endovascular abdominal aneurysm repair and stent-graft procedure in dissected and ulcerated aorta. It seems to be superior in characterization of the type of endoleaks and can be established in order to reduce iodized contrast agent and radiation exposure in follow-up. In contrast to CTA scan CHI can be offered to patients with chronic renal insufficiency and allows a dynamic examination and a perfusion analysis.

Pre-surgical evaluation of ICA-stenosis using 3D power Doppler, 3D color coded Doppler sonography, 3D B-flow and contrast enhanced B-flow in correlation to CTA/MRA: first clinical results.

AIM: Pre-surgical evaluation of the extent of internal carotid artery stenosis (ICA) according to NASCT criteria using digital 3D ultrasound methods. MATERIAL/METHODS: In a prospective study, 25 patients (54-88 years, mean 75) with neurological deficits and the diagnosis of ICA stenosis underwent pre-surgical ultrasound examination using Color Coded Duplex Sonography (CCDS), 3D CCDS, 3D power Doppler, 3D B-flow, contrast enhanced 3D B-flow, and CTA/MRA. Ultrasound was performed by an experienced examiner with a multifrequency linear transducer (6-9 MHz, Logiq 9, GE). After bolus injection of 2.4 ml Sonovue i.v., low mechanical index technique (MI<0.16) was used for contrast enhanced 3D B-flow. As reference method for evaluation of the extent of ICA stenosis each patient underwent CTA (multislice CT, Sensation 16, Siemens) and/or MRA (1.5 T, Symphony Siemens). Indications for surgery (carotid EEA) followed the NASCET criteria. All images were interpreted and evaluated independently by two observers with three measurements of the degree of the ICA stenosis. For assessment of the extent of stenosis a 10%-scale from 50% to 99% was used. Statistical analysis was performed using Spearman Correlation and Wilcoxon Signed Rank Test with a significance threshold of p<0.05. RESULTS: Assessment of the extent of ICA stenosis during surgery and in CTA/MRA displayed a range from 60% to 99% (mean 80%). Non significant differences were found with paired Wilcoxon test only for 3D B-flow with and without contrast medium (p<0.05). Correlation with surgical evaluation regarding the extent of ICA stenosis using Spearman correlation teat was 0.77 for B-scan, 0.90 for 3D CCDS, 0.84 for 3D Power Doppler, 0.91 for B-flow and 0.93 for contrast enhanced 3D B-flow. When circular calcifications were present, contrast enhanced flow detection of 3D B-flow proved to be useful. Visualisation of intrastenotic variances of severe and profound stenosis (70-99%) without blooming and reverberation artefacts was possible only with 3D B-flow. This facilitates the detection of the morphology of plaques ulcers as an embolic source. CONCLUSION: In correlation with surgery and CTA/MRA, a valid evaluation of the extent and morphology of ICA stenosis using 3D B-flow, with and without contrast medium, is feasible.

Evaluation of microcirculation of free flaps of the lower leg by contrast harmonic imaging (CHI) with time intensity curve (TIC) analysis.

PURPOSE: The aim of the prospective study was to evaluate the macro- and microcirculation in the center and periphery of free flaps with high resolution vascular ultrasound. MATERIAL: Fifteen patients with free parascapular flaps after lower limb trauma were examined six months postoperative. All ultrasound investigations were performed by one experienced examiner with a multi-frequency linear transducer (5-9 MHz, Logiq 9, GE). Flow evaluation was angle-optimized using digital image technology with the color coded Doppler sonography (CCDS) with measurement of the peak systolic, peak diastolic flow velocities and the resistance index (RI). Contrast harmonic imaging (CHI) with time intensity curve (TIC) analysis was used for quantitative evaluation of the tissue perfusion. Through a peripheral cubital cannula, a first bolus injection was made of 2.4 ml Sonovue to evaluate the perfusion near the flap center and the distal part of the flap. RESULTS: The combined analysis of all 15 patients showed in the center and in the periphery of the flap a significant increase (p<0.01; Wilcoxon signed rank test) of the perfusion (relative units = RUs) in the period of 90-120 s after contrast medium application (center: baseline perfusion 2.23+/-0.31 RUs to 5.25+/-0.90 RUs after contrast medium; periphery: baseline perfusion 3.07+/-0.44 RUs to 5.80+/-0.57 RUs after contrast medium). The separate analysis of the non-bypass group (n=9) and bypass group (n=6) showed a clearly higher central flap perfusion after contrast medium application for the bypass group. The combined analysis of all patients showed RI-values amounting to 0.79+/-0.03. The RI-values of the bypass group were significantly higher than RI-values of the non-bypass group (p<0.05; t-test; p<0.05; Mann-Whitney rank sum test). CONCLUSION: The high-resolution ultrasound represents an ideal method for detection of the flow and patency of the bypass and the small vessels of the free flap. The patency of microvascular anastomosis as well as the perfusion and microcirculation in different flap territories and tissue layers can be investigated using dynamic contrast-enhanced ultrasound with subtraction modalities.

Retrojugular versus ventrojugular approach to carotid bifurcation for eversion endarterectomy: a prospective randomized trial.

OBJECTIVES: The aim of this prospective randomized study was to demonstrate the comparability of retrojugular access for carotid eversion endarterectomy compared to the conventional ventrojugular procedure. PATIENTS AND METHODS: Due to the expected minor and major complication rate of 5% in patients undergoing carotid surgery, a patient cohort of 600 study patients was planned. All patients underwent standard preoperative and postoperative assessment including clinical investigation and fiberoptic laryngoscopy. The 6 month follow-up examination included an evaluation of patient contentment, a duplex scan, clinical investigation and a fiberoptic laryngoscopy. RESULTS: After the first interim evaluation of 101 patients, the study was stopped because of a significant increase in temporary ipsilateral vocal cord motility dysfunction in the retrojugular access group (31% vs. 6%, p=0.0014). This early postoperative impairment was, however, not statistically significant at the follow-up examination at 6 months (2.4% vs. 0%). No other significant differences concerning major complications (death or stroke), other cranial nerve injuries, wound healing, or patient satisfaction was observed neither in the early postoperative phase nor at follow up. CONCLUSION: Due to the high incidence of temporary ipsilateral vocal cord dysfunction in patients undergoing retrojugular exposure of the carotid artery, we recommend the conventional ventrojugular approach, which can be performed by incision along the anterior border of the sternomastoid muscle or by transversal skin incision.

Intraarterial gadolinium-enhanced magnetic resonance angiography of the renal arteries in humans: feasibility, contrast agent reduction, and accuracy for detection of stenoses.

OBJECTIVE: Feasibility of intraarterial MR angiography of the renal arteries and comparison of the accuracy of intraarterial MR angiography with selective intraarterial digital subtraction angiography (DSA) for detection of stenoses. MATERIALS AND METHODS: Ten consecutive patients (mean, 68 years) with suspected renal artery stenosis underwent a digital subtraction angiography and an intraarterial gadolinium-enhanced MR angiography, performed on a 1.5-T system. For intraarterial MR angiography 60 ml diluted contrast agent (10 ml gadodiamide in 50 ml 0.9% saline solution) was injected through a conventional angiography catheter placed in the suprarenal abdominal aorta using a flow rate of 3.5 ml/s. A three-dimensional (3D) gradient-echo sequence was performed. Differences in the quantitative measurement of stenoses of lesions between DSA and intraarterial MR angiography were evaluated by three observers. Overall impression of the intraarterial MR angiography was documented on a four-point scale (1 = excellent to 4 = poor). Interobserver variability was calculated. RESULTS: Intraarterial MR angiography of the renal arteries was feasible in all patients (100%) with a mean overall impression of all images of 1.8 (SD: 0.71). One of 9 accessory renal arteries was not visualized with intraarterial MR angiography. The overall sensitivity/specificity for detection of significant stenoses (>or=50% stenosis) were 83%/87%. Interobserver variability of intraarterial MR angiography ranged between fair and substantial (0.359-0.622). CONCLUSION: Intraarterial MR angiography of the renal arteries in humans is feasible and has an acceptable sensitivity in detecting stenoses using injections of diluted contrast agent at concentrations as low as 17%.

Early experience shows rapid shrinking of abdominal aortic aneurysms after endovascular treatment with Anaconda device.

BACKGROUND: The Anaconda prosthesis is a new endovascular device for abdominal aortic aneurysms repair. AIM: of the study was to evaluate successful access to the arterial site, safety and efficacy of stent placement and fixation, assessment of endoleaks, patency of the graft due to twists, kinks or obstruction within the first 30 days after the procedure. Secondary objectives were the assessment of clinical success after 6 months due to graft patency and aneurysm exclusion without endoleak as well as the continuing clinical success without showing aneurysm expansion or any graft failure. PATIENTS AND METHODS: Between 2003 and 2006 a total of 14 patients with infrarenal aortic aneurysm (median diameter prior to endovascular treatment: 56.7 mm (range: 50 to 70 mm) were treated with the Anaconda endovascular device. 8 of these patients were treated in accordance to a prospective Phase II clinical study protocol (Anaconda ANA 004). 6 more patients received the same endovascular device after CE-certification. RESULTS: Primary and secondary objectives were achieved in 12 of 14 patients after 6 months. In one patient insertion of the graft system was impossible due to kinking and circular calcification of the iliac arteries. Iliac access utilizing an alternative stent graft system (Cook, Zenith) was also unsuccessful. This patient underwent a conversion to open surgery and died. Another patient died 6 months after treatment unrelated to the procedure. A significant reduction of the median aneurysm diameter from 56.7 to 49.0 mm (range: 45 to 54 mm) was achieved after 6 months (p = 0.05). No endoleak was seen in the follow up. CONCLUSIONS: Early results show that he Anaconda endovascular device for aneurysm repair is a safe and effective device for patients with suitable abdominal aortic aneurysms and proper distal access vessels which results in significant aneurysm diameter decrease and a low complication rate after 6 months of follow-up.

[Diagnosis and endovascular treatment of proximal endograft instability after thoracic endografting]. / Diagnostik und endovaskuläre Behandlung einer proximalen Endograft-Instabilität nach thorakalem Endostent.

Four cases of proximal endostent instability after endovascular tube graft treatment of thoracic aortic disease using the TAG Gore system are reported. This potentially hazardous complication is characterized by a lack of attachment of the device to the small curvature of the aortic arch. Towering up against the hemodynamic forces in this area, the endograft could collapse and occlude the aorta. To identify this complication we recommend to perform an early postinterventional CT-scan with parasagittal reconstruction and an observation of the proximal endograft by fluorography. Endovascular solutions for the treatment of this complication may be either a proximal extension by another endograft or fixation of the proximal endograft by a balloon expandable Palmaz stent.

Value of high resolution ultrasound and contrast enhanced US pulse inversion imaging for the evaluation of the vascular integrity of free-flap grafts.

OBJECTIVE: The aim of this study was to evaluate the clinical value of color coded Doppler sonography (CCDS) and contrast-enhanced harmonic imaging (CHI) for ultrasound (US) monitoring the integrity of free-flap vascular grafts. Patency of microvascular anastomoses and perfusion as well as microcirculation of the transplanted tissue were analysed. PATIENTS AND METHODS: Fifteen free parascapular flap grafts performed over a period of three years by a single surgeon were examined with CCDS and CHI. The patients (12 male, 3 female) ranged in age from 16 to 60 years (average age 40+/-12). The follow-up period ranged from two weeks to 2.5 years. CCDS were performed with a multifrequency linear transducer (5-10 MHz, Logiq 9, GE) with 3D flow detection. For detection and characterization, B scan of the flap tissue was compared to tissue harmonic imaging (THI) and Cross Beam with Speckle Reduction Imaging (SRI). US Pulse Inversion Harmonic Imaging (PIHI) after bolus injection of 2.5 ml Sonovue was used for contrast enhancement. RESULTS: Border and tissue structure of the flaps could be detected best in all 15/15 cases using Cross Beam Technology with SRI and THI. Correlations were found for flow parameters of the common femoral artery, popliteal artery and lower leg artery to the anastomotic vessels. 3D imaging with CCDS facilitated flow detection of elongated and small anastomotic vessels in 4/15 cases. Contrast-enhanced US with PIHI allowed dynamic flow detection of the microcirculation of the transplanted tissue over a depth of up to 3 cm with quantitative perfusion curves of the tissue microcirculation. Reduced US contrast enhancement with modified perfusion curves was seen in 2/15 cases with low anastomic flow in CCDS. CONCLUSION: Assessment of microvascular perfusion with contrast-enhanced ultrasound can provide valuable information on free flap viability. Contrast-enhanced US enables dynamic and quantitative flow detection of free flap tissue.

[Popliteal vein entrapment in patients with unspecific symptoms of venous insufficiency]. / Belastungs- oder lageabhängige Schwellung der Wadenmuskulatur mit Spannungsgefühl und krampfartigen Schmerzen.

Popliteal vein entrapment must be taken in consideration in patients with symptoms of venous insufficiency. Leg edema, swelling, calf pain, and muscle cramps are all unspecific signs. Most patients thus far have presented with deep vein thrombosis or chronic venous insufficiency. Popliteal entrapment syndrome must be taken into account in younger patients in whom predisposing factors are absent and chronic calf swelling is notable. Diagnosis is easily confirmed by noninvasive stress testing with duplex imaging and pencil Doppler probe placed over the posterior tibial artery. Additionally, digital subtraction angiography with the foot in neutral and dorsi plantarflexion is recommended for arterial entrapment. Surgery is advisable for treatment and can be done without significant morbidity. In asymptomatic patients, we suggest using the term "popliteal vein entrapment phenomenon." We describe different etiologies of popliteal vein entrapment in three cases and present a review of the literature.

Effect of combining nicotinamide as a PARS-inhibitor with selective iNOS blockade during porcine endotoxemia.

OBJECTIVE: To investigate the effects of combined selective inducible nitric oxide synthase (iNOS) inhibition using 1400 W with nicotinamide (NAD) as a PARS-inhibitor on hepato-splanchnic hemodynamics, O(2) kinetics, and energy metabolism during hyperdynamic porcine endotoxemia. DESIGN: Prospective, randomized, controlled, interventional experiment. SETTING: Animal research laboratory. SUBJECTS: Seventeen domestic pigs. INTERVENTIONS: After 12 h of continuous i.v. endotoxin (LPS) infusion 17 pigs received either no drug (CON, n=9) or 1400 W, titrated to maintain mean arterial pressure (MAP) at pre-endotoxin level, plus 10 mg.kg.h NAD ( n=8;). Measurements were obtained before, 12 h, 18 h, and 24 h after starting LPS infusion. MEASUREMENTS AND RESULTS: In addition to systemic and pulmonary hemodynamics and gas exchange, we measured hepatic arterial and portal venous blood flow, liver and portal venous drained viscera O(2) exchange, ileal mucosal-arterial PCO(2) gap, and portal as well as hepatic venous lactate/pyruvate ratios. Expired NO and plasma nitrate levels were assessed as a parameter of NO production. Without affecting cardiac output, therapy maintained MAP and blunted the LPS-induced rise in expired NO levels, attenuated the progressive fall in liver lactate clearance, and blunted the impairment of hepato-splanchnic redox state. The rise of ileal mucosal-arterial PCO(2) gap was not influenced. CONCLUSIONS: Combining selective iNOS inhibition with NAD as a PARS blocker may prevent circulatory failure and attenuate the detrimental consequences of LPS in intestinal and hepatocellular energy metabolism. Given the potential hepatotoxicity of high-dose NAD treatment, more potent PARS blockers with higher selectivity might further enhance the benefit of this therapeutic approach.

Effects of selective iNOS inhibition on gut and liver O2-exchange and energy metabolism during hyperdynamic porcine endotoxemia.

We have previously demonstrated that non-selective nitric oxide synthase (NOS) inhibition did not reverse the LPS-induced deterioration of hepato-splanchnic energy status in porcine endotoxic shock. Therefore, this study investigated the effect of selective inducible NOS (iNOS) inhibition using 1400 W on intestinal and liver perfusion, O2 kinetics, and energy metabolism during hyperdynamic porcine endotoxemia. Intravenous E. Coli LPS was continuously infused over 24 h concomitant with fluid resuscitation. After 12 h of endotoxemia, continuous intravenous infusion of 1400 W was started until the end of the experiment and was titrated to maintain mean blood pressure (MAP) at baseline levels. Twelve, 18, and 24 h after starting LPS, we measured hepatic arterial and portal venous blood flow, ileal mucosal-arterial PCO2 gap, portal as well as hepatic venous lactate/pyruvate ratios, and endogenous glucose production rate. Expired NO and plasma nitrate levels were assessed as a measure of NO production. 1400 W decreased LPS-induced increase in expired NO and allowed for the maintenance of MAP without modification of cardiac output. Despite unchanged regional macrocirculation, 1400 W prevented the progressive rise of ileal mucosal-arterial PCO2 gap, significantly improved the LPS-induced impairment of hepato-splanchnic redox state, and blunted the decline in liver lactate clearance. Increased glucose production rate was not influenced. Thus, the selective iNOS inhibition with 1400 W prevented circulatory failure and largely attenuated otherwise progressive LPS-induced deterioration of intestinal and hepatocellular energy metabolism.

Effects of combined selective iNOS inhibition and peroxynitrite blockade during endotoxemia in pigs.

We investigated the effect of mercaptoethylguanidine (MEG, 3 mg kg(-1)h(-1)), a combined selective inducible nitric oxide synthase (iNOS) inhibitor, a peroxynitrite and oxygen free radical scavenger with cyclooxygenase-inhibitor properties on intestinal and hepatic perfusion, O2 exchange, and metabolism during long-term hyperdynamic porcine endotoxemia. MEG was started 12 h after onset of endotoxemia. At baseline and after 12, 18, and 24 h of endotoxemia, hepatic arterial and portal venous blood flow, ileal mucosal-arterial PCO2 gap, portal and hepatic venous lactate/pyruvate ratio, free glutathione (GSH), and 8-isoprostanes were measured. Expired NO and plasma nitrate levels were assessed as well. MEG blunted the endotoxin-induced increase in expired NO and prevented the progressive fall in blood pressure without affecting cardiac output. It attenuated both systemic and regional venous acidosis without influencing the impairment of hepatosplanchnic metabolism nor counteracting the increase in GSH levels. In our model MEG failed to beneficially affect variables of oxidative stress.

Increased ileal-mucosal-arterial PCO2 gap is associated with impaired villus microcirculation in endotoxic pigs.

OBJECTIVE: To investigate whether an increased ileal-mucosal-arterial PCO2 gap (delta PCO2) during hyperdynamic porcine endotoxemia is associated with impaired villus microcirculation. DESIGN: Prospective, randomized, controlled, experimental study. SETTING: Animal research laboratory. ANIMALS: Twenty-two domestic pigs. INTERVENTIONS: After baseline measurements, anesthetized and ventilated pigs received continuous i.v. endotoxin (ETX, n = 12) for 24 h or placebo (SHAM, n = 10). MEASUREMENTS AND RESULTS: Before, as well as 12 and 24 h after, the start of endotoxin or saline portal venous blood flow (QPV, ultrasound flow probe) and lactate/pyruvate ratios (L/P), the ileal-mucosal-arterial delta PCO2 (fiberoptic sensor) and bowel-wall capillary hemoglobin O2 saturation (%Hb-O2-cap, remission spectrophotometry) were assessed together with intravital video records of the ileal-mucosal microcirculation (number of perfused/heterogeneously perfused/unperfused villi) using orthogonal polarization spectral imaging (CYTOSCAN A/R) via an ileostomy. At 12 and 24 h endotoxin infusion, about half of the evaluated villi were heterogeneously or unperfused which was paralleled by a progressive significant increase of the ileal-mucosal-arterial delta PCO2 and portal venous L/P ratios, whereas QPV as well as both the mean %Hb-O2-cap and the %Hb-O2-cap frequency distributions remained unchanged. By contrast, in the SHAM-group, mucosal microcirculation was well-preserved, and none of the other parameters were influenced. CONCLUSIONS: We conclude that an increased ileal-mucosal-arterial delta PCO2 during porcine endotoxemia is related to impaired villus microcirculation. A putative contribution of disturbed cellular oxygen utilization resulting from "cytopathic hypoxia" may also assume importance.

Effects of nicotinamide, an inhibitor of PARS activity, on gut and liver O2 exchange and energy metabolism during hyperdynamic porcine endotoxemia.

OBJECTIVE: To investigate the effects of nicotinamide (NIC), an inhibitor of poly(ADP-ribose) synthetase (PARS), on intestinal and liver perfusion, O2 kinetics, and energy metabolism over 24 h of hyperdynamic porcine endotoxemia. DESIGN: Prospective, randomized, controlled experimental study with repeated measures. SETTING: Animal laboratory in a university hospital. SUBJECTS: Sixteen pigs, divided into two groups: nine endotoxemic animals without therapy (CON); seven animals treated with NIC. INTERVENTIONS: Pigs were anesthetized, mechanically ventilated, and instrumented. Intravenous E. Coli LPS was continuously infused over 24 h concomitant with fluid resuscitation. After 12 h of endotoxemia continuous i.v. infusion of NIC (10 mg/kg per hour) was administered until the end of the experiment. MEASUREMENTS AND RESULTS: All animals developed hyperdynamic circulation with sustained increase in cardiac output and progressive fall in mean arterial pressure. NIC maintained blood pressure without affecting CO. Hepato-splanchnic macrocirculation was not modified by the treatment. Nevertheless, although NIC attenuated the progressive rise of ileal mucosal-arterial PCO2 gap, it failed to improve portal venous L/P ratio, a marker of the overall energy state of the portal venous drained viscera. Similarly, neither the increased hepatic venous L/P ratio nor the simultaneous drop in hepatic lactate uptake were influenced by NIC. CONCLUSIONS: Although NIC maintained hemodynamic stabilization during long-term endotoxemia, it was unable to improve LPS-induced deterioration of the hepato-splanchnic energy metabolism. More potent and selective PARS inhibitors are needed to elucidate the role of a PARS-dependent pathway in a clinically relevant models of sepsis.

Lipid reductions by low-density lipoprotein apheresis: a comparison of three systems.

There are currently three established low-density lipoprotein (LDL) apheresis systems: immunoadsorption, heparin-induced extracorporeal LDL precipitation (HELP), and dextran sulfate. We treated the same patient with all three systems and compared the lipid reductions achieved. A total of 135 consecutive treatments were studied, 57 with immunoadsorption, followed by 30 with HELP and 48 with dextran sulfate adsorption. The mean plasma volume (mean +/- SD) treated was 4.9 +/- 0.05, 3.08 +/- 0.091, and 3.39 +/- 0.71 L, respectively. The LDL-cholesterol (LDL-C) reduction was 75.5% +/- 7.4%, 61.6% +/- 5.1%, and 57.1% +/- 12.4%, respectively (P < .001 for immunoadsorption vHELP and dextran sulfate). The mean removal efficiency (mass removed/plasma volume treated) for LDL-C was 1.0 +/- 0.12, 1.42 +/- 0.25, and 1.15 +/- 0.21 g/L, respectively (P < .001 for HELP v immunoadsorption and dextran sulfate). The mean LDL-C plasma concentration before apheresis was 199 +/- 23.9, 201 +/- 25.7, and 186 +/- 28 mg/dL, respectively (P < .001 for dextran sulfate adsorption v immunoadsorption and HELP). Among the three LDL apheresis systems, immunoadsorption caused the greatest percent reduction in LDL-C, while HELP eliminated LDL-C from the plasma most efficiently. Dextran sulfate was similar to HELP in terms of LDL-C reduction, and its removal efficiency was similar to immunoadsorption. Dextran sulfate was also associated with the lowest pretreatment plasma LDL-C concentration.

[Laryngo-hypopharyngo-esophagectomy in advanced hypopharyngeal carcinoma. Is radical surgery intervention still justified today?]. / Laryngo-Hypopharyngo-Osophagektomie beim fortgeschrittenen Hypopharynxkarzinom. Ist dieser radikalchirurgische Eingriff heute noch gerechtfertigt?

Minimal invasive laser surgery with preservation of the organs is well established in the treatment of hypopharynx carcinoma. In cases of advanced tumors of the hypopharynx, which can not be managed by laser surgery, the combined radio-chemo therapy becomes the treatment of choice because of the low morbidity and the comparable results. The indication for an operative procedure, which means loss of larynx and oesophagus, is seen more and more restrictively. From 1993 to 1997 101 patients with advanced neoplasm of the hypopharynx or larynx (larynxcarcinoma T4; hypopharynx carcinoma T3-T4 with N > 2b) were treated in the Department of Otolaryngology of the University of Regensburg. 5 of these patients underwent a laryngohypopharyngoesophagectomy. Only patients with a severe dysfunction of the larynx (dyspnea, dysphagia, aspiration) were selected for this procedure. Postoperative complications were: one insufficiency of anastomosis with secondary bleeding and five pleura effusions. In all cases postoperative radiation began within six weeks after the operation. All patients were nourished orally when they were discharged from hospital. The mean follow up was 21 months. During this time none of the patients died. In one case pulmonary metastasis was found after 11 months. In another case a regional recurrence was diagnosed after 11 months and was removed by operation. No local recurrence was found at that time. This operative procedure can be done only in experienced and well trained medical centers. Furthermore excellent cooperation of the operating teams and strong regard to the selection criteria is obligatory.

Tumour necrosis factor-alpha and interleukin-10 production in septic patients and the regulatory effect of plasma.

OBJECTIVE: To investigate the capacity of patients' whole blood to produce proinflammatory and antiinflammatory cytokines in severe sepsis and to relate abnormalities to the effect of the patients' plasma on cytokine production in healthy donor blood. DESIGN: Open, prospective clinical study. SETTING: Teaching hospital, Germany. PATIENTS: Ten patients in the surgical intensive care unit with shock and a systemic inflammatory response syndrome (SIRS), a mean APACHE II score of 27, and dysfunction of at least two organ systems at the time of investigation, resulting in 70% mortality. MAIN OUTCOME MEASURES: Tumour necrosis factor-alpha (TNF-alpha) and interleukin-10 (IL-10) concentrations. RESULTS: TNF-alpha and IL-10 production of the whole blood in response to lipopolysaccharide (LPS) was reduced from 2000 pg/ml to 90 pg/ml and from 9163 pg/ml to 622 pg/ml, respectively (p < 0.01). When the plasma of these septic patients was added to the whole blood cells of healthy donors TNF-alpha production decreased by 38% to 1238 pg/ml (p < 0.01) and IL-10 production by 36% to 5857 pg/ml (p = 0.03). CONCLUSION: The effect of plasma from septic patients on the cytokine production in healthy donor blood cells paralleled the decreased production of proinflammatory TNF-alpha and antiinflammatory IL-10 in the whole blood of septic patients. Efforts to modulate cytokine production in septic patients therefore need to take account of the signals from the plasma as well as the functional capacity of the cells.

Depression of tumor necrosis factor-alpha, interleukin-6, and interleukin-10 production: a reaction to the initial systemic hyperactivation in septic shock.

Sepsis remains a major cause of mortality in surgical intensive care units. Patients who survive the initial shock phase but die weeks later from multiple organ dysfunction still are a challenge to basic and clinical research. We addressed whether fulminant sepsis results in rapid changes (24 h) in the cellular capacity to produce cytokines in whole blood of septic patients on further stimulation after the initial systemic inflammatory response. Interleukin (IL)-6 plasma concentrations from 279 pg/mL to 5979 pg/mL confirmed the presence of a systemic inflammatory response. Anti-inflammatory IL-10 concentrations up to 275 pg/mL were detected, but there was no biologically active tumor necrosis factor-alpha (TNFalpha) detectable (by bioassay) at the time of investigation. On stimulation with Escherichia coli ex vivo, pro-inflammatory TNFalpha (130 pg/mL), IL-6 (4061 pg/mL), and anti-inflammatory IL-10 (711 pg/mL) production were markedly depressed in all patients compared with controls (2339 pg/mL, 50,319 pg/mL, and 9654 pg/mL, respectively). Septic shock resulted in early depression of the capacity for pro- and anti-inflammatory cytokine production. Monitoring of this effect, including its relationship to outcome, may offer a target variable for therapeutic efforts to maintain or restore adequate immune reactions to improve survival.