Incidence of clinically symptomatic pneumothorax in ultrasound-guided infraclavicular and supraclavicular brachial plexus block.

The use of periclavicular brachial plexus block as regional anaesthesia for surgical procedures on the upper extremity is common. However, the proximity of the pleura results in a risk of pneumothorax. Without ultrasound monitoring, the pneumothorax risk has been reported to be as high as 6.1%. We conducted a prospective, observational study to examine the risk of pneumothorax in 6366 ultrasound-guided periclavicular plexus blocks. All patients with a clinically manifest and radiologically confirmed pneumothorax were analysed. Clinically symptomatic pneumothorax occurred in four patients (0.06%; 95% CI 0.001-0.124), in three of them after a two-day latency period. Ultrasound guidance does therefore appear to reduce the risk of pneumothorax. Although all of the anaesthesiologists involved in the complications had previously performed fewer than 20 blocks, we are not able to confirm that a block experience ≤ 20 is a significant risk factor. Faulty image-setting, inability to obtain a view of the needle tip and inadequate supervision are likely to be important risk factors.

[Ultrasound-guided peripheral regional anesthesia : placement and dosage of local anesthetics]. / Ultraschallgesteuerte periphere Regionalanästhesie : Applikationsort und Dosierung des Lokalanästhetikums.

Ever since the use of ultrasound guidance in regional anesthesia became more and more popular in recent years, it seemed obvious that so-called intraneural puncture and injection of local anesthetics was much more common than previously assumed. However, neurologic damage was not seen very often. The ultrasound-guided imaging of the nerves showed that intraneural injection has to be seen as an overall term. This term must be characterized in more detail in accordance with nerve anatomy and morphology. Various studies demonstrated that if intraneural puncture occured the needle usually took a path away from the fascicles (intraneural perifascicular), while intraneural transfascicular puncture seemed relatively rare and intraneural intrafascicular placement of the needle even more uncommon. As long as the needle is placed intraneurally but in an extrafascicular fashion a safe injection and the absence of neurologic damage can be assumed. However, if nerve fascicles are affected neurologic dysfunction can occur. In studies investigating the minimal effective local anesthetic volume needed for successful nerve block, a relevant reduction of injected volume was still achieved by intentionally applying the local anesthetic circumferentially around the outermost nerve layer rather than injecting it into neural structures. As an intraneural -intrafascicular injection carries the risk of nerve injury associated with a decrease in quality of life, the potential of ultrasound guidance in regional anesthesia should be considered. Circumferential administration of local anesthetic rather than creating a single point injection appears to be advantageous.

Changes in the extracellular matrix of the autogenous patellar tendon graft after posterior cruciate ligament reconstruction: a biochemical study in sheep.

The left knee joints of female German sheep were operated, replacing the posterior cruciate ligament by the central third of the patellar tendon. After 2, 6, 16, 26 and 52 weeks the graft of the operated leg as well as the contralateral central third of the patellar tendon and the posterior cruciate ligament were dissected and used for biochemical analysis. The total glycosaminoglycan content in grafts increases within the first year up to 5 fold and is higher than that of the patellar tendon, but is lower than that of the cruciate ligament. The distribution pattern of glycosaminoglycans differ in the posterior cruciate ligament and the patellar tendon. In cruciate ligament the main components are chondroitin sulfate (76%) and hyaluronan (15%). In the patellar tendon a higher portion of dermatan sulfate (approx. 16%) was found, next to 52% chondroitin sulfate and 22% hyaluronan. During the examination time the grafts show changes in the concentration and the distribution pattern of glycosaminoglycans. The chondroitin sulfate content increases during the experimental period from 1.4 +/- 1.2 mumol/g dry weight (d.w.) to 8.7 +/- 2.9 mumol/g d.w. After 1 year the chondroitin sulfate content in the graft does not differ significantly from that of the cruciate ligament. In the grafts the concentration of chondroitin (non sulfated) increases after 6 weeks up to 1.3 +/- 0.6 mumol/g d.w. in comparison to the value after 2 weeks (0.2 +/- 0.1 mumol/g d.w.) and also in the other groups (16, 26 and 52 weeks) it remains significantly increased. After 1 year the dermatan sulfate content in the graft has increased up to the fifth-fold compared to the value after 2 weeks and is higher than in the patellar tendon and in the cruciate ligament. In graft the hyaluronan content (1.0 +/- 0.4 mumol/g d.w. does not differ significantly in the groups 2, 6, 16, 26 and 52 weeks after operation, but in all five groups it is lower than in the cruciate ligament (2.4 +/- 1.0 mumol/g d.w.). Dermatan and heparan sulfate are not or only little detected in all three tissues. The distribution pattern of glycosaminoglycans in graft shows chondroitin sulfate and dermatan sulfate being the major parts of glycosaminoglycans with a slight increase of these components in the different groups during the experimental period. Hyaluronan makes up to 24 +/- 5% of the whole content of glycosaminoglycans after 2 weeks and decrease to 8 +/- 1% after 52 weeks.(ABSTRACT TRUNCATED AT 400 WORDS)

Histochemical aspects of the proteoglycans of patellar tendon autografts used to replace the posterior cruciate ligament.

In the female German black-faced sheep the posterior cruciate ligament was replaced by a free patellar tendon autograft and after 2, 6, 16, 26 and 52 weeks tissue samples of the graft's center (axial region far from bones) were removed for histochemistry and electron microscopy. To localize the proteoglycans Alcian Blue and 0.3 M MgCl2 were added to the fixative solution. The distribution of the proteoglycans in the graft was compared to that of a normal patellar tendon and of a normal posterior cruciate ligament. In the patellar tendon spindle-shaped cells predominated and proteoglycans appeared as short filaments at regular intervals between the collagen fibrils. In the posterior cruciate ligament chondroid cells and long filaments in a net-work-like arrangement were seen. In the patellar tendon autografts short interfibrillar filaments prevailed after 2, 6 and 16 weeks. After 26 weeks and particularly after 52 weeks long filaments also appeared. Digestion with Chondroitinase ABC, AC and Hyaluronidase suggested that the short filaments were PGs containing dermatan sulfate. In grafts, in the early phases the fibroblasts predominated, while in the late phases mainly chondroid cells were observed. The grafts showed aspects of the normal posterior cruciate ligament. However, differences remained, for example the thin collagen fibrils, which could represent one of the reasons for a secondary graft failure.

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.

Effect of dopexamine on hepatic metabolic activity in patients with septic shock.

Hepato-splanchnic metabolic activity is seen to be related to regional blood flow and oxygen/substrate availability in patients with sepsis. Catecholamines, which may modulate metabolic activity perse, are common to stabilize hemodynamics. We studied the effect of a dopexamine-induced increase in splanchnic blood flow (Qspl) on regional metabolic rate in 10 patients with septic shock requiring norepinephrine to maintain mean arterial pressure (>60 mmHg). Splanchnic blood flow was determined using the indocyanine-green method with hepatic venous sampling. We determined the hepato-splanchnic lactate, pyruvate, alanine, and glutamine turnover and the lactate/pyruvate and ketone body ratio as well as the endogenous glucose production (EGP) using the stable isotope approach. Qspl increased from 0.86 (0.79-1.15) to 0.96 (0.92-1.33) L/min/m2, not influencing any parameter of metabolic activity. We speculate that this finding is due to altered beta-adrenoreceptor-mediated thermogenic effects due to the interplay of different beta-sympathomimetics at the receptor site.

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.

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.

Hepato-splanchnic metabolic effects of the stable prostacyclin analogue iloprost in patients with septic shock.

OBJECTIVE: To evaluate the effects of the stable prostacyclin analogue iloprost on hepato-splanchnic blood flow, oxygen exchange and metabolism in patients with septic shock. DESIGN: Prospective clinical study. SETTING: Intensive care unit in a university clinic. PATIENTS: Eleven patients with septic shock requiring norepinephrine to maintain mean arterial pressure above 70 mmHg. INTERVENTIONS: Iloprost was incrementally infused to increase cardiac index by 15%. MEASUREMENTS AND MAIN RESULTS: Splanchnic blood flow (Qspl) was measured using the steady-state indocyanine-green infusion technique and endogenous glucose production rate (EGP) using a stable isotope approach. Systemic and splanchnic oxygen consumption (VO2), the hepato-splanchnic uptake rates of the glucose precursors lactate, pyruvate, alanine and glutamine, the hepatic venous redox state and gastric mucosal-arterial PCO2 gradients were determined. After a baseline measurement, iloprost infusion was started. After 90 min all measurements were repeated and a third measurement was obtained after another 90 min following iloprost withdrawal. Qspl (baseline I: 0.82/0.75-1.08 l x min x m2; iloprost: 0.94/0.88-1.29 l x min x m2; baseline II: 0.87/0.74-1.09 l x min x m2) and splanchnic oxygen delivery (baseline I: 122/103-166 ml x min x m2; iloprost: 134/117-203 ml x min x m2; baseline II: 130/98-158 ml x min x m2) significantly increased. While systemic VO2 significantly increased (baseline I: 139/131-142 ml x min x m2; iloprost: 147/136-164 ml x min x m2; baseline II: 143/133-154 ml x min x m2) splanchnic VO2 increased in 9 of 11 patients which, however, did not reach statistical significance. EGP significantly decreased (baseline I: 23/16-26 micromol x kg x min; iloprost: 16/14-21 micromol x kg x min; baseline II: 18/12-20 micromol x kg x min), whereas all other parameters of energy metabolism remained unchanged. CONCLUSION: In patients with septic shock an iloprost-induced increase in cardiac index increased splanchnic blood flow and shifted oxygen utilization from the energy requiring de novo glucose production rate to other oxygen-demanding metabolic pathways.

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.

Positive role of immune nutrition on metabolism in sepsis and multi-organ failure.

Critically ill patients with systemic inflammatory response syndrome (SIRS) and multi-organ failure are at great risk of nosocomial infections due to a reduced immune status. There is growing evidence from in vitro studies and animal models that the reduced immune response might be improved by the so-called immunomodulatory nutrition. Based on these studies there are now some commercially available enteral or parenteral solutions with immunomodulatory substrates, such as n-3 polyunsaturated fatty acids (PUFAs), arginine and nucleotides. Recently, enteral nutrition with this experimental formula reduced the hospital length of stay and the frequency of acquired infections in critically ill patients. The increasing knowledge about the metabolic effects of these nutritions offers therapeutic potential for the future, and might reduce the mortality of critically ill patients from nosocomial infections. However, at present, studies are necessary to find the best time for beginning and duration of the feeding. In addition, the optimal dosage and composition of these pharmacologically active substances has to be investigated.

Splanchnic and renal blood flow after cardiopulmonary resuscitation with epinephrine and vasopressin in pigs.

In laboratory investigations, vasopressin given during CPR resulted in improved vital organ blood flow when compared with epinephrine. Given the profound and long lasting vasopressor effects of vasopressin, we tested the hypothesis that vasopressin given during CPR would result in renal and splanchnic hypoperfusion in the post-resuscitation period when compared with epinephrine. After 4 min of ventricular fibrillation, 16 pigs were randomly assigned to receive either 0.045 mg x kg(-1) epinephrine or 0.4 U X kg(-1) vasopressin before defibrillation. Splanchnic and renal blood flow were measured 30, 90, and 240 min after restoration of spontaneous circulation (ROSC) in the epinephrine and vasopressin groups and in a control group of eight pigs using radiolabeled microspheres. Hepatic blood flow was measured before arrest and 30, 90, and 240 min after ROSC by means of indocyanine green infusion. Thirty minutes after ROSC, renal and adrenal blood flow were significantly lower in the vasopressin group (300 [273-334] and 256 [170-284] ml X min(-1) x 100 g(-1)) (median and 25th and 75th percentile) as compared with the epinephrine group (370 [346-429] and 360 [326-420] ml x min(-1) x 100 g(-1); P < 0.05). Pancreatic, intestinal, and hepatic blood flow were not significantly different in animals after receiving epinephrine or vasopressin. In comparison to epinephrine, vasopressin given during cardiac arrest impairs renal and adrenal perfusion temporarily but does not lead to intestinal or hepatic hypoperfusion in the post-resuscitation phase.

Simultaneous determination of plasma enrichments of 1-13C- and 15N-labelled phenylalanine and tyrosine.

A methylchloroformate derivative was used for the simultaneous determination of plasma enrichments of 1-13C-phenylalanine, 1-13C-tyrosine, 15N-phenylalanine and 15N-tyrosine by gas chromatography/mass spectrometry. All four tracer enrichments could be measured in a single GC run. A specific ion fragment was obtained for each tracer. This approach allowed an easy determination of the "tracer to tracee ratios". Each ion fragment could be measured with an appropriate single-to-noise ratio and precision in samples obtained from 100 microliters plasma. The derivatization consists of a fast one-step reaction. Therefore it is well suited for studies involving a large number of samples, such as non-steady state bolus studies.

Determination of 13CO2/12CO2 ratio by IRMS and NDIRS.

Breath tests using 13C-labelled substrates require the measurement of 13CO2/12CO2 ratio in breath gas samples. Next to isotope ratio mass spectrometry (IRMS), which is very sensitive but also complex and expensive, alternatively isotope selective nondispersive infrared spectrometry (NDIRS) can be used to determine the 13CO2/12CO2 ratio in expired breath. In this study we compared NDIRS- with IRMS-results to investigate whether the less expensive and very simply to operate NDIRS works as reliable as IRMS. For this purpose we applicated 1- 13C-Phenylalanine to patients with advanced liver cirrhosis and healthy volunteers and took duplicated breath samples for IRMS and NDIRS at selected time points. Our data show a good correlation between these two methods for a small number of samples as required for simple breath tests. Longer series, where repeated measurements are required on the NDIRS instrument lead to a decreasing correlation. This indicates the superiority of IRMS concerning 13CO2-kinetics over longer time periods.

Determination of (13)CO(2)/(12)CO(2) Ratio by IRMS and NDIRS.

Abstract Breath tests using (13)C-labelled substrates require the measurement of (13)CO(2)/(12)CO(2) ratio in breath gas samples. Next to isotope ratio mass spectrometry (IRMS), which is very sensitive but also complex and expensive, alternatively isotope selective nondispersive infrared spectrometry (NDIRS) can be used to determine the (13)CO(2)/(12)CO(2) ratio in expired breath. In this study we compared NDIRS- with IRMS-results to investigate whether the less expensive and very simply to operate NDIRS works as reliable as IRMS. For this purpose we applicated 1-(13)C-Phenylalanine to patients with advanced liver cirrhosis and healthy volunteers and took duplicated breath samples for IRMS and NDIRS at selected time points. Our data show a good correlation between these two methods for a small number of samples as required for simple breath tests. Longer series, where repeated measurements are required on the NDIRS instrument lead to a decreasing correlation. This indicates the superiority of IRMS concerning (13)CO(2)-kinetics over longer time periods.

Comparison between the oral and intravenous L-[1-13C]phenylalanine breath test for the assessment of liver function.

To simplify the L-[1-13C]phenylalanine breath test which is used to assess liver function the tracer is usually given orally, and CO2 production rate is estimated. In 12 healthy volunteers and 10 liver cirrhotics we compared the oral approach with i.v. tracer administration combined with measurement of individual CO2 production rate. The 13CO2/12CO2 enrichment was assessed by isotope-ratio mass spectrometry. After i.v. [1-13C]phenylalanine application exhaled 13C recovery per minute peaked within 10 minutes (controls: 0.17 +/- 0.06%; cirrhotics: 0.05 +/- 0.02%, p < 0.01). The oral approach yielded comparable separation between 30-60 minutes, with average peak values being 0.18 +/- 0.03% and 0.06 +/- 0.03% (p < 0.01), respectively. Variable gastrointestinal resorption kinetics after oral application probably causes this difference.

Effect of a dopexamine-induced increase in cardiac index on splanchnic hemodynamics in septic shock.

In 12 patients with hyperdynamic septic shock we studied the effect of dopexamine, a combined dopamine and beta-adrenergic agonist, on hepatosplanchnic hemodynamics and O(2) exchange. All patients required noradrenaline to maintain mean arterial pressure > 60 mm Hg (noradrenaline >/= 0.04 microg x kg(-1) x min(-1)) with a cardiac index >/= 3.0 L/min/m(2). Splanchnic blood flow (Qspl) was measured using primed continuous infusion of indocyanine green dye with hepatic venous sampling. In addition tonometric gastric mucosal-arterial and gastric mucosal-hepatic venous P CO(2) gradients were assessed as indicators of regional energy balance. After 90 min of stable hemodynamics a first measurement was obtained. Then dopexamine infusion was titrated (1-4 microg x kg(-1) x min(-1)) to increase cardiac output by approximately 25% (20-30%). After 90 min all measurements were repeated, and dopexamine was withdrawn followed by a third measurement. Median Qspl (0.86/1.23-0. 66 versus 0.96/1.42-0.85 L/min/m (2) [median value/25th-75th percentiles], p < 0.05) increased whereas the fractional contribution of Qspl to total blood flow decreased (21/28-13 versus 19/28-12%, p < 0.05). Although both global and regional oxygen delivery (DO(2)) consistently increased, neither global or regional V O(2) nor PCO(2) gradients were significantly affected. In patients with septic shock and ongoing noradrenaline treatment dopexamine seems to have no preferential effects on hepatosplanchnic hemodynamics, O(2) exchange, or energy balance.

Phenylalanine kinetics in healthy volunteers and liver cirrhotics: implications for the phenylalanine breath test.

Expired 13CO2 recovery from an oral l-[1-13C]phenylalanine ([13C]Phe) dose has been used to quantify liver function. This parameter, however, does not depend solely on liver function but also on total CO2 production, Phe turnover, and initial tracer distribution. Therefore, we evaluated the impact of these factors on breath test values. Nine ethyl-toxic cirrhotic patients and nine control subjects received intravenously 2 mg/kg of [13C]Phe, and breath and blood samples were collected over 4 h. CO2 production was measured by indirect calorimetry. The exhaled 13CO2 enrichments were analyzed by isotope ratio mass spectrometry and the [13C]Phe and l-[1-13C]tyrosine enrichments by gas chromatography-mass spectrometry. The cumulative 13CO2 recovery was significantly lower in cirrhotic patients (7 vs. 12%; P < 0.01), in part due to lower total CO2 production rates. Phe turnover in cirrhotic patients was significantly lower (33 vs. 44 micro mol. kg(-1). h(-1); P < 0.05). When these extrahepatic factors were considered in the calculation of the Phe oxidation rate, the intergroup differences were even more pronounced (3 vs. 7 micro mol. kg(-1). h(-1)) than those for 13CO2 recovery data. Also, the Phe-to-Tyr conversion rate, another indicator of Phe oxidation, was significantly reduced (0.7 vs. 3.0 micro mol. kg(-1). h(-1)).