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P Radermacher

Publications and source records attributed to P Radermacher.

At least 19 recordsLinked to original sources
PubMed2006

[Treatment strategies for acute smoke inhalation injury].

Most fatalities from fires are not due to burns, but are a result of inhalation of toxic gases produced during combustion. Fire produces a complex toxic environment, involving flame, heat, oxygen depletion, smoke and toxic gases such as carbon monoxide and cyanide. As a wide variety of synthetic materials is used in buildings, such as insulation, furniture, carpeting, electric wiring covering as well as decorative items, the potential for poisoning from inhalation of products of combustion is continuously increasing. The present review describes the pathophysiologic effects from smoke inhalation injury as well as strategies for emergency treatment on scene and in the intensive care setting.

Carbon Monoxide Poisoning↗
PubMed2003

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.

Amidines↗
PubMed2003

Arterial blood gases during diving in elite apnea divers.

Elite apnea divers have considerably extended the limits of dive depth and duration but the mechanisms allowing humans to tolerate the compression- and decompression-induced changes in alveolar gas partial pressures are still not fully understood. Therefore we measured arterial blood gas tensions and acid-base-status in two elite apnea divers during simulated wet dives lasting 3 : 55 and 5 : 05 minutes, respectively. Arterial pO2 followed the compression-(from 13.8/16.9 kPa before the dive to 30 kPa at the start of the bottom time) and decompression-induced (from 13.7/21.0 kPa to 3.3/4.9 kPa immediately after surfacing) variations of ambient pressure, while the arterial pCO2 remained within the physiologic range (3.0/3.9 kPa before diving vs. 5.7/5.9 kPa at the end of the bottom time), probably due to the CO2 storage capacity of the blood. These findings may help to explain why humans can sustain deep and long apnea dives without major increases in respiratory drive.

Acid-Base Equilibrium↗
PubMed2003

Catecholamines in the treatment of septic shock: effects beyond perfusion.

OBJECTIVE: To review the metabolic effects of sympathomimetic agents in the septic patient. DATA SOURCES: A review of articles reported on the metabolic effects of the commonly used sympatho-mimetic agents in the critically ill patient. SUMMARY OF REVIEW: Sepsis and septic shock are clinically charcterized mainly by derangements of cardiocirculatory function. Mainstay therapeutic interventions for haemodynamic stabilisation are adequate volume resuscitation and vasoactive agents. These, however, may be linked with additional effects on energy balance and cell metabolism. As well as the haemodynamic effects, specific metabolic effects need to be considered for optimal vasopressor treatment during severe sepsis and septic shock. This review highlights the typical haemodynamic and metabolic alterations associated with the commonly used sympathomimetic drugs in these conditions. CONCLUSIONS: Sepsis and septic shock are linked with profound metabolic alterations. An additional impact of vasoactive therapy on metabolism has to be taken into account when using these agents to treat severe sepsis and septic shock.

Journal Article↗
PubMed2002

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)).

Adult↗
PubMed2001

Hepatic oxygen exchange and energy metabolism in hyperdynamic porcine endotoxemia: effects of the combined thromboxane receptor antagonist and synthase inhibitor DTTX30.

OBJECTIVE: We compared the effects of thromboxane receptor antagonist and synthase inhibitor DTTX30 on systemic and liver blood flow, oxygen (O2) exchange and energy metabolism during 24 h of hyperdynamic endotoxemia with untreated endotoxemia. DESIGN: Prospective, randomized, experimental study with repeated measures. SETTING: Investigational animal laboratory. SUBJECTS: Twenty-seven domestic pigs: 16 during endotoxemia with volume resuscitation alone; 11 with endotoxemia, volume resuscitation and treatment with DTTX30. INTERVENTIONS: Continuous infusion of Escherichia coli lipopolysaccharide (LPS) for 24 h together with volume resuscitation. After 12 h of endotoxemia, DTTX30 was administered as a bolus of 0.12 mg kg-1 followed by 12 h continuous infusion of 0.29 mg kg-1 per h. MEASUREMENTS AND RESULTS: DTTX30 effectively counteracted the endotoxin-associated increase in TXB2 levels and increased 6-keto-PGF1 alpha with a significant shift of the thromboxane/prostacyclin ratio towards predominance of prostacyclin. DTTX30 prevented the significant progressive endotoxin-induced decrease of mean arterial pressure (MAP) below baseline while maintaining cardiac output (CO), and increased the fractional contribution of liver blood flow to CO without an effect on either hepatic O2 delivery or O2 uptake. The mean capillary hemoglobin O2 saturation (HbO2) on the liver surface and HbO2 frequency distributions remained unchanged as well. CONCLUSIONS: DTTX30 significantly attenuated the endotoxin-induced derangements of cellular energy metabolism as reflected by the diminished progressive decrease in hepatic lactate uptake rate and a blunted increase in hepatic venous lactate/pyruvate ratios. While endotoxin significantly increased the endogenous glucose production (EGP) rate, EGP returned towards baseline levels in the DTTX30-treated group. Thus, in our model DTTX30 resulted in hemodynamic stabilization concomitant with improved hepatic metabolic performance.

Animals↗
PubMed2001

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.

Animals↗
PubMed2001

Is it feasible to monitor total hepatic blood flow by use of transesophageal echography? An experimental study in pigs.

OBJECTIVES: Total hepatic venous blood flow is determined by the common hepatic arterial blood flow and the venous outflow from stomach, spleen, pancreas, small intestine, and bowel, collected by the portal vein, and thus represents overall splanchnic perfusion. We investigated whether transesophageal echography (TEE) can provide a method for bedside assessment of hepatic venous blood flow useful as a noninvasive method for measuring splanchnic perfusion in clinical practice. DESIGN AND SETTING: Experimental study in 15 anesthetized and ventilated pigs in an animal research laboratory. INTERVENTIONS: TEE-derived calculations of hepatic venous blood flow were compared with liver blood flow measurements using perivascular ultrasound flow probes surgically positioned on portal vein and common hepatic artery. Parameters were determined at baseline and after modulating splanchnic perfusion by either PEEP maneuver (15 cmH2O) or intravenous epinephrine (0.1 microgram kg-1 min-1). MEASUREMENTS AND RESULTS: Diameter (d) and velocity time integral (VTI) of all three hepatic veins were determined by TEE, heart rate (HR) was derived from electrocardiography and flow subsequently calculated as Q = pi.(d/2)(2).0.57.VTI.HR. Regression analysis of matched TEE and flow probe values showed a significant linear relationship (r2 = 0.698). Bias analysis revealed a systematic underestimation of liver blood flow by TEE, possibly due to use of 0.57 as correction factor for mean velocity, while changes in liver blood flow were reliably detected. CONCLUSION: TEE offers a noninvasive approach for monitoring hepatic perfusion and may be used in patients.

Animals↗
PubMed2001

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.

Animals↗
PubMed2001

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.

Adult↗
PubMed2001

Influence of prone position on gastric mucosal-arterial PCO2 gradients.

OBJECTIVE: To evaluate the effects of mechanical ventilation in the prone position on gastric mucosal-arterial PCO2 gradients. DESIGN: Prospective clinical study. SETTING: Intensive care unit in a university clinic. PATIENTS: Twenty-five patients requiring mechanical ventilation. The physician in charge indicated the turning manoeuver for the individual patient. MEASUREMENTS/RESULTS: In addition to routine measurements of global hemodynamics and gas exchange we determined: 1) intragastric pressure; and 2) gastric mucosal-arterial PCO2 difference. After a baseline measurement in the supine position patients were turned to the prone position. After 60', 120', a median of 6.5 h (2-10 h) in the prone position, and again after 60' in the supine position, all measurements were repeated. Global hemodynamics remained unaltered throughout the study. While gastric mucosal-arterial PCO2 gradients did not change significantly during the first 60 min in the prone position, they significantly increased during the following 60 min [median/percentile: baseline: 6 (1 to -3); 60': 7 (15-5); 120': 13 (20-8) mmHg]. The median intragastric pressure was not significantly affected [baseline: 10 (13-5); 60': 12 (16-8); 120': 11 (13-7) mmHg], but 9 of the 11 patients in whom intragastric pressure increased during the first 60 min in the prone position also showed significantly increased PCO2 gradients (P < 0.01). CONCLUSION: Mechanical ventilation in the prone position may be affiliated with increased tonometric gastric mucosal-arterial PCO2 gradients depending on the effect on intraabdominal pressure. Measuring intraabdominal pressure and/or gastric mucosal PCO2 via a nasogastric tube therefore may help to detect adverse effects of this ventilatory strategy.

Analysis of Variance↗
PubMed2001

Stress response during weaning after cardiac surgery.

We compared the effects of weaning using synchronized intermittent mandatory ventilation (SIMV) with the use of biphasic positive airway pressure (BIPAP) on the stress response, oxygen uptake (VO2) and work of breathing (WOB) in 10 patients after aortocoronary bypass surgery. All three ventilatory settings were investigated in each patient, for example, volume-controlled mechanical ventilation immediately before weaning was followed, in randomized order, by both SIMV and BIPAP. In addition to routine monitoring of continuous and respiratory state, we measured VO2, WOB, and pressure-time product (PTP) as well as the plasma concentrations of epinephrine, norepinephrine, ACTH, cortisol, vasopressin, and prolactin. Although respiratory rate (f), WOB and PTP were greater with both SIMV and BIPAP when compared with control, other variables did not change with the ventilatory mode. In conclusion, weaning from mechanical ventilation using partial support modes does not affect the postoperative stress response in patients who have had uncomplicated cardiac surgery.

Coronary Artery Bypass↗
PubMed2001

Arterial and mixed venous xenon blood concentrations in pigs during wash-in of inhalational anaesthesia.

There are no data available on the kinetics of blood concentrations of xenon during the wash-in phase of an inhalation anaesthesia aiming at 1 MAC end-expiratory concentration. Therefore, we anaesthetized eight pigs with continuous propofol and fentanyl and measured arterial, mixed venous and end-expiratory xenon concentrations by gas chromatography-mass spectrometry 1, 2, 3, 4, 5, 7, 10, 15, 20, 30, 60 and 120 min after starting the anaesthetic gas mixture [67% xenon/33% oxygen; 3 litre x min(-1) during the first 10 min, thereafter minimal flow with 0.48 (SD 0.03) litre x min(-1)]. End-expiratory xenon concentrations plateaued (defined as <5% change from the preceding value) at 64 (6) vol% after 7 min, and arterial and mixed venous xenon concentrations after 5 and 15 min respectively. The highest arterio-venous concentration difference occurred after 3 min. Using the Fick principle, we calculated a mean xenon uptake of 3708 (829) and 9977 (3607) ml after 30 and 120 min respectively.

Anesthesia, Inhalation↗
PubMed2001

Involvement of heme oxygenase-1 (HO-1) in the adaptive protection of human lymphocytes after hyperbaric oxygen (HBO) treatment.

Accumulating evidence suggests that HO-1 plays an important role in cellular protection against oxidant-mediated cell injury. Our previous studies on hyperbaric oxygen (HBO; i.e. exposure to pure oxygen under high ambient pressure) indicated clearly increased levels of HO-1 in lymphocytes of volunteers 24 h after HBO treatment (1 h at 1.5 bar). Experiments with the comet assay (alkaline single cell gel electrophoresis) revealed that the same cells were almost completely protected against the induction of DNA damage by a repeated exposure or in vitro treatment with H(2)O(2) 24 h after the first HBO. In order to further investigate the role of HO-1 in HBO-induced adaptive response, we now performed experiments with isolated human lymphocytes exposed to HBO in vitro (2 h at 3 bar). Our results show that also under cell culture conditions, lymphocytes exhibit an adaptive protection similar to that observed in our previous work with healthy human subjects. The time-course of HO-1 induction proceeds in parallel to the development of an adaptive protection against the induction of oxidative DNA damage. A comparable protection was not seen in V79 cells, indicating a specific difference between the two investigated cell systems. Treatment with the specific HO-1 inhibitor tin-mesoporphyrin IX (SnMP) led to a complete abrogation of HBO-induced adaptive protection in human lymphocytes. Our results indicate a functional involvement of HO-1 in the adaptive protection of human lymphocytes against the induction of oxidative DNA damage. The exact mechanism by which HO-1 contributes to an adaptive response remains to be elucidated.

Adaptation, Physiological↗
PubMed2001

Metabolic effects of vasoactive agents.

After adequate volume resuscitation, the mainstay of therapy in critically ill patients with shock is treatment with vasoactive substances to restore haemodynamics or to improve regional perfusion. These agents include adrenoceptor agonists with inotropic combined with either vasoconstricting or vasodilating effects, and predominantly vasodilating drugs such as prostacyclin and related compounds. However, vasoactive agents not only affect the cardiovascular system, but also have profound metabolic effects. The interdependence of vasoactive drugs with metabolism may be relevant regarding adequate oxygen and substrate delivery to cover actual organ needs. Therefore, the profiles of these metabolic effects have to be considered during their therapeutic administration.

Journal Article↗
PubMed2001

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.

Adult↗
PubMed2001

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.

6-Ketoprostaglandin F1 alpha↗