[Can anesthesiologic research maintain its position in the international literature?].
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Publications and source records attributed to P Radermacher.
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OBJECTIVE: To investigate the impact of exogenous beta-adrenergic receptor stimulation on splanchnic blood flow, oxygen kinetics, glucose-precursor flux, and liver metabolism in septic shock. DESIGN: Prospective trial. SETTING: University hospital intensive care unit. PATIENTS: Six patients with hyperdynamic (cardiac index >4.0 L/min/m2) septic shock, all requiring norepinephrine to maintain blood pressure >65 mm Hg. INTERVENTIONS: We compared norepinephrine and phenylephrine titrated to achieve similar systemic hemodynamics and gas exchange. Splanchnic hemodynamics, oxygen kinetics, and metabolic parameters were measured before, during, and after replacing norepinephrine with phenylephrine. MEASUREMENTS AND MAIN RESULTS: Splanchnic blood flow and oxygen kinetics were derived from the steady-state indocyanine-green clearance based on hepatic dye extraction and arterial and hepatic venous blood gases. Endogenous glucose production rate was derived from the plasma appearance rate of stable-isotope-labeled glucose using a primed-constant infusion. Splanchnic lactate, alanine (high-performance liquid chromatography) uptake, and hepatic monoethylglycinexylidide (MEGX) (fluorescence polarization immunoassay) formation rates were calculated from splanchnic blood flow and arterial-hepatic venous concentration differences. Replacing norepinephrine with phenylephrine induced no change in systemic hemodynamics or gas exchange. While splanchnic oxygen consumption and alanine uptake rate remained unaffected, splanchnic blood flow, oxygen delivery, and lactate uptake rate were significantly decreased. Glucose production rate also decreased significantly. A return to norepinephrine restored splanchnic blood flow, oxygen delivery, and lactate uptake rate to baseline values, while glucose production rate remained depressed. Hepatic MEGX formation rate was not influenced during the investigation. CONCLUSIONS: Exogenous beta-adrenergic receptor stimulation determines splanchnic blood flow, oxygen delivery, and glucose precursor flux but not splanchnic oxygen utilization in septic shock. Gluconeogenesis is not directly affiliated to hepatosplanchnic oxygen kinetics. The different response of glucose and MEGX production rates, metabolic pathways of the periportal and perivenous region, may document intrahepatic heterogeneity associated with hepatocellular metabolic compartmentation.
BACKGROUND/AIM: During major abdominal surgery, mesenteric traction (MT) may result in hemodynamic instability mainly due to endogenous prostacyclin release. Gastric intramucosal pH (pHi) and PiCO2 are indicators of splanchnic tissue perfusion with a predictive value for the postoperative outcome. We investigated the influence of MT on gastric pHi and on postoperative outcome in patients undergoing pancreas surgery. METHODS: Forty-six consecutive patients scheduled for pancreas surgery were investigated. We registered hemodynamics and pHi by gastric tonometry and documented postoperative outcome (complications, hospital stay). Baseline data (T0) were recorded after skin incision. Further assessments followed 30, 60 and 120 min after intentional MT (T1-3) and at the end of surgery (T4). RESULTS: Thirty-three patients demonstrated a decrease in mean arterial pressure (MAP) following MT, whereas 13 patients showed entirely stable hemodynamics. The significant reduction in MAP in patients with an MT response was not associated with changes in pHi as compared to patients with no response (stable MAP) (T0 7.34 +/- 0.08 vs. 7.35 +/- 0.06; T1 7.34 +/- 0.05 vs. 7.32 +/- 0.07; T2 7.32 +/- 0. 05 vs. 7.31 +/- 0.08; T3 7.32 +/- 0.05 vs. 7.32 +/- 0.07; T4 7.26 +/- 0.1 vs. 7.27 +/- 0.08; mean +/- SD, MT response vs. no response). Neither MT response nor gastric intramucosal acidosis as evidenced by a pHi <7.32 at the end of surgery predicted postoperative complications or longer hospital stay. CONCLUSION: No deterioration of gastric pHi was found, which could reflect acceptable splanchnic perfusion and oxygenation despite systemic blood pressure reactions in patients experiencing an MT response.
Hyperbaric Oxygen (HBO) therapy is a kind of medical treatment in which a patient breathes 100% of oxygen inside a pressure chamber while the pressure of the chamber is increased to a point higher than sea level pressure. It is strongly based on clearly defined physical laws and physiological regularities. For the clinical use of HBO therapy, according to international recommendations, there are several commonly accepted indications in which HBO either is the only causative life-saving kind of treatment, or is an essential and oftenly decisive component of a comprehensive interdisciplinary intensive care therapy. Among potential adverse effects, barotrauma of the lungs and especially oxygen toxicity to the central nervous system have to be mentioned. Clinical use of HBO therefore requires special knowledge of its effects, risks, and adverse effects, a clear and distinct indication, and the ability and skills to keep complications under control by means of intensive care or emergency medical measures. The clinical use of hyperbaric oxygen with its interdisciplinary-like character of emergency medicine or intensive care therapy therefore should be an additional, most interesting field of activity for the anaesthesiologist.
OBJECTIVE: To investigate the effect of preoperative ibuprofen administration on renal function during and after infrarenal aortic surgery under thoracolumbar epidural anaesthesia (EPA). DESIGN: A prospective randomised, double-blinded clinical study. SETTING: Operation room and intensive care unit in a university hospital. PATIENTS: Twenty-six consecutive patients scheduled for elective infrarenal aortic surgery. INTERVENTIONS: The patients were prospectively randomised to receive 400 mg ibuprofen intravenously (i.v.) or a placebo aliquot before surgery. MEASUREMENTS AND RESULTS: We assessed renal function by calculating creatinine clearance, and fractional sodium excretion before surgery (baseline), 1 h after cross-clamping (intraoperative), 6 h after cross-clamping (postoperative) and 24 h after cross-clamping (on the 1 st postoperative day). At each point in time, we additionally registered haemodynamics and determined the plasma concentration of 6-keto-PGF1alpha (stable metabolite of prostacyclin, PGI2), bicyclic PGE2 (stable metabolite of PGE1 E2), active renin, aldosterone and vasopressin by radioimmunoassays. Throughout the observation period the renal function parameters mostly remained within the normal range without a significant difference between ibuprofen- and placebo-treated patients (creatinine clearance: baseline 41 +/- 3 vs 38 +/- 6, intraoperative 57 +/- 8 vs 64 +/- 11, postoperative 64 +/- 9 vs 56 +/- 9, first postoperative day 43 +/- 5 vs 47 +/- 6 ml x min x m(-2), means +/- SEM). The plasma levels of 6-keto-PGF1alpha (68 +/- 8 vs 380 +/- 71* ng x l(-1)), bicyclic PGE2 (57 +/- 5 vs 88 +/- 9* ng x l(-1)) and vasopressin (14 +/- 7 vs 45 +/- 10* ng x l(-1), p < 0.0125), however, were significantly higher during the intraoperative period in the placebo-treated patients. CONCLUSION: The inhibition of endogenous prostaglandin release by ibuprofen does not substantially impair renal function during infrarenal aortic surgery under EPA.
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OBJECTIVE: To analyze work of breathing (WOB) imposed by the respirators EVITA-2, EVITA-4 (Drägerwerk, Lübeck, Germany) and SV 300 (Siemens-Elema, Sweden) as well as inspiratory flow response and expiratory flow resistance during continuous positive airway pressure (CPAP). DESIGN: Five study conditions on a lung model (CPAP at 0, 5, and 10 mbar, CPAP 5 mbar plus pressure support 2 mbar with both EVITA models, and CPAP 5 mbar with decreasing levels of flow and pressure trigger sensitivity with the SV 300) and three randomized study conditions in nine patients recovering from open heart surgery (condition A: EVITA-2, CPAP 5 mbar; condition B: SV 300, CPAP 5 mbar, flow trigger; condition C: SV 300, pressure trigger-4 mbar). SETTING: University hospital intensive care unit and laboratory of pulmonary physiology. MEASUREMENTS AND RESULTS: At each study condition we measured WOB, pressure-time product (PTP), WOB and PTP imposed (WOBimposed and PTPimposed), tidal volume, minute ventilation, respiratory rate, inspiratory trigger time, trigger pressure, trigger PTP, duration of inspiration, mean and peak inspiratory flow, and the delay from the onset of inspiration to peak inspiratory flow. Since the SV 300 automatically generates an additional pressure support of 2 cm H2O PTP, WOB, WOBimposed, and PTPimposed were higher with the EVITA-2 and EVITA-4 regardless of the trigger sensitivity set on the SV 300. The difference was neutralized with both types of EVITA ventilator by adding 2 mbar of pressure support during CPAP in order to achieve comparable conditions. Inspiratory flow response was faster with both EVITA models, expiratory flow resistance was higher with the SV 300. Decrements of trigger sensitivity with the SV 300 accelerated the flow response. CONCLUSIONS: Under similar conditions, no difference in WOBimposed was observed, although inspiratory flow response and expiratory flow resistance differed substantially between the three ventilators tested. Trigger sensitivity plays a minor role in determining PTP and WOB but has major influence on flow.
OBJECTIVE: Today, sepsis syndrome is the leading cause of death in adult, non-coronary intensive care units (ICUs) and is of great clinical importance. The purpose of this review was to evaluate recent prospective studies concerning the short- and long-term prognosis of patients suffering from systemic inflammatory-response syndrome (SIRS), sepsis, severe sepsis and septic shock. It has been shown in multicentre prospective surveys that 1% and 0.3% of all patients admitted to hospitals suffer, respectively, from bacteraemia alone and bacteraemia with severe sepsis. This rate increases, of course, when only admissions to the ICUs are considered: the above-mentioned rates increase then by a factor of 8 and 30, respectively. Thus, approximately 10% of patients in the ICU suffer from sepsis, 6% from severe sepsis and 2-3% from septic shock. SIRS occurs more frequently and its occurrence ranges from 40% to 70% of all patients admitted to ICUs. Thereby, 40-70% suffering from SIRS progress to a more severe septic-disease state. The overall prognosis is still poor, despite the recent advances in ICU treatment. The mortality rate of SIRS ranges from 6% to 7% and in septic shock amounts to over 50%. In particular, abdominal sepsis exhibits the highest mortality rate with 72%. The long-term prognosis is equally poor; only approximately 30% survived the first year after hospital admission. CONCLUSION: The prognosis of sepsis and septic shock remains poor, despite the advances in ICU treatment. Although prognostic factors have been identified for some patients, groups have not yet been able to identify the immediate or long-term prognosis for the majority of these septic patients.
OBJECTIVES: To investigate the impact of arterial hypertension on cardiac function during aortic cross-clamping and declamping. DESIGN: Prospective study. SETTING: University hospital. PARTICIPANTS: Twenty treated hypertensive males with slight left ventricular hypertrophy and 10 normotensive controls undergoing elective repair of an abdominal aortic aneurysm. INTERVENTIONS: Using transesophageal echocardiography, the mitral inflow profile was evaluated during aortic cross-clamping and declamping. MEASUREMENTS AND MAIN RESULTS: During the clamping period, the ratio of peak atrial to peak early filling velocity (PA/PE) was significantly higher in the hypertensive patients. One minute after aortic cross-clamping, mean arterial pressure (MAP) and pulmonary artery occlusion pressure significantly increased in the hypertensive patients, whereas they did not change in the normotensive group. Cardiac index and heart rate significantly decreased after cross-clamping, and increased after clamp release in both groups. PA/PE significantly dropped in both groups after aortic declamping, and returned to baseline values thereafter. MAP also decreased significantly in both groups after clamp release, but the fall of MAP tended to be more pronounced in the hypertensive patients. CONCLUSIONS: In the treated hypertensive patients, more pronounced hemodynamic and echocardiographic responses to aortic cross-clamping probably mirror the altered diastolic left ventricular function in these patients. With respect to intraoperative management, however, the treated hypertensive patients did not react grossly differently from the normotensive controls.
We investigated hepatic blood flow, O2 exchange and metabolism in porcine endotoxic shock (Control, n = 8; Endotoxin, n = 10) with administration of hydroxyethylstarch to maintain arterial pressure (MAP)>60 mmHg. Before and 12, 18 and 24 h after starting continuous i.v. endotoxin we measured portal venous and hepatic arterial blood flow, intracapillary haemoglobin O2 saturation (Hb-O2%) of the liver surface and arterial, portal and hepatic venous lactate, pyruvate, glycerol and alanine concentrations. Glucose production rate was derived from the plasma isotope enrichment during infusion of [6,6-2H2]-glucose. Despite a sustained 50% increase in cardiac output endotoxin caused a progressive, significant fall in MAP. Liver blood flow significantly increased, but endotoxin affected neither hepatic O2 delivery and uptake nor mean intracapillary Hb-O2% and Hb-O2% frequency distributions. Endotoxin nearly doubled endogenous glucose production rate while hepatic lactate, alanine and glycerol uptake rates progressively decreased significantly. The lactate uptake rate even became negative (P<0.05 vs Control). Endotoxin caused portal and hepatic venous pH to fall significantly concomitant with significantly increased arterial, portal and hepatic venous lactate/pyruvate ratios. During endotoxic shock increased cardiac output achieved by colloid infusion maintained elevated liver blood flow and thereby macro- and microcirculatory O2 supply. Glucose production rate nearly doubled with complete dissociation of hepatic uptake of glucogenic precursors and glucose release. Despite well-preserved capillary oxygenation increased lactate/pyruvate ratios reflecting impaired cytosolic redox state suggested deranged liver energy balance, possibly due to the O2 requirements of gluconeogenesis.
The tonometric measurement of the arterial-intramucosal PCO2-difference and the calculation of the intramucosal pH is currently the only parameter which is available in the clinical routine for the assessment of perfusion, oxygen kinetics and metabolic activity of the patho-splanchnic region. Since this region with its unique both parallel and serial blood supply net comprises several organs with different metabolic performance, among which moreover the synthetic activity of the liver has to be taken into account, tonometric data have to be interpreted independently from blood flow and oxygen transport and uptake in this region. In fact, tonometry is an integrative parameter for perfusion, oxygenation and cellular energy balance. Therefore, it more completely reflects the complex anatomical and physiological conditions.
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.
BACKGROUND: The incidence of perioperative bradyarrhythmias in patients with bifascicular or left bundle branch block (LBBB) and the influence of an additional first-degree atrioventricular (A-V) block has not been evaluated with 24-h Holter electrocardiographic monitoring. Therefore the authors assessed the rate of block progression and bradyarrhythmia in these patients. METHODS: Patients (n = 106) with asymptomatic bifascicular block or LBBB with or without an additional first-degree A-V block scheduled for surgery under general or regional anesthesia were enrolled prospectively. Three patients were excluded. Of the 103 remaining, 56 had a normal P-R interval and 47 had a prolonged one. Holter monitoring (CM2, CM5) was applied to each patient just before induction of anesthesia and was performed for 24 h. The primary endpoint of the study was the occurrence of block progression. As secondary endpoints, bradycardias < 40 beats/min with hemodynamic compromise (systolic blood pressure < 90 mmHg) or asystoles > 5 s were defined. RESULTS: Block progression to second-degree A-V block and consecutive cardiac arrest occurred in one case of LBBB without a prolonged P-R interval Severe bradyarrhythmias with hypotension developed in another eight patients: asystoles > 5 s occurred in two cases and six patients had bradycardias < 40/min. Pharmacotherapy was successful in these eight patients. There was no significant difference for severe bradyarrhythmias associated with hemodynamic compromise between patients with and without P-R prolongation (P = 1.00). CONCLUSIONS: In patients with chronic bifascicular block or LBBB, perioperative progression to complete heart block is rare. However, the rate of bradyarrhythmias with hemodynamic compromise proved to be relevant. Because an additional first-degree A-V block did not increase the incidence of severe bradyarrhythmias and pharmacotherapy by itself was successful in nearly all cases, routine prophylactic insertion of a temporary pacemaker in such patients should be questioned.
OBJECTIVE: To determine the efficacy and safety of using natural platelet-activating factor receptor antagonist (PAFra), BN 52021, to treat patients with severe Gram-negative bacterial sepsis. DESIGN: A prospective, randomized, double-blind, placebo-controlled, multicenter clinical trial. SETTING: Fifty-nine academic medical center intensive care units in Europe. PATIENTS: Six hundred nine patients with severe sepsis, suspected to be related to Gram-negative bacterial infection, who received PAFra or placebo. INTERVENTIONS: Patients were randomized to receive either a dose of PAFra (120 mg iv) every 12 hrs over a 4-day period or placebo over a 4-day period. MEASUREMENTS AND MAIN RESULTS: The patients were well matched at study entry for severity of illness and for risk factors known to influence the outcome of sepsis. Among all randomized patients, the 28-day, all-cause mortality rate was 49% (152/308) in the placebo group, and 47% (140/300) in the PAFra group (p=.50). When analyzed on the basis of the previously defined target population, the 28-day, all-cause mortality rate was 50% (115/232) in the placebo group and 44% (94/212) in the PAFra group, yielding a 12% reduction in mortality rate (p=.29). In patients with documented infection involving other organisms, there was no difference between treated and placebo groups. When the outcomes of organ dysfunctions were examined in the overall population and in the documented Gram-negative bacterial infection population, the number of patients who resolved hepatic dysfunction tended to be higher in the treated group than in the placebo group (p=.06). The number of adverse events reported were not different between the two groups. CONCLUSIONS: A 4-day administration of the studied PAFra (BN 52021) failed to demonstrate a statistically significant reduction in the mortality rate of patients with severe sepsis suspected to be related to Gram-negative bacterial infection. If PAFra treatment has any therapeutic activity in severe Gram-negative bacterial sepsis, the incremental benefits are small and will be difficult to demonstrate in a patient population as defined by this clinical trial.
BACKGROUND: Angiotensin-converting enzyme (ACE) inhibitors are well established as long-term antihypertensives and have also been proved useful in hypertensive emergencies. Therefore, we investigated whether intraoperative i.v. enalaprilat may reduce the incidence of perioperative hypertensive reactions in coronary artery bypass grafting (CABG). METHODS: Thirty-eight male patients chronically treated for arterial hypertension and scheduled for CABG randomly and double-blindly received either enalaprilat 30 micrograms.kg-1 or NaCl 0.9% at the time of skin incision. Intraoperatively, increases of mean arterial pressure (MAP) > 85 mmHg or > 80 mmHg during cardiopulmonary bypass (CPB) were treated by an urapidil bolus. The total intraoperative amount of urapidil was documented for both groups. Systemic and pulmonary hemodynamics as well as the plasma levels of epinephrine, norepinephrine, arginine vasopressin and renin were measured intraoperatively and up to 2 h after admission to the intensive care unit. RESULTS: Mean arterial pressure, cardiac index and systemic vascular resistance did not differ between the enalaprilat and the control group. Renin plasma levels significantly increased after infusion of enalaprilat and did not change in the placebo group. Catecholamine and arginine vasopressin plasma levels increased significantly during CPB and remained high in the postoperative period without any intergroup difference. The same amount of urapidil had to be given in the two groups to maintain MAP below the defined limit. CONCLUSION: We conclude that infusing 30 micrograms.kg-1 enalaprilat in patients chronically treated for arterial hypertension does not prevent hypertensive reactions during CABG.
BACKGROUND: We investigated the vasopressor hormone response following mesenteric traction (MT) with hypotension due to prostacyclin (PGI2) release in patients undergoing abdominal surgery with a combined general and epidural anesthesia. METHODS: In a prospective, randomized, placebo-controlled study we administered 400 mg ibuprofen (i.v.) in 42 patients scheduled for abdominal surgery. General anesthesia was combined with epidural anesthesia (T4-L1). Before as well as 5, 15, 30, 45, and 90 min after MT we recorded plasma osmolality, hemodynamics and measured 6-keto-PGF1 alpha (stabile metabolite of PGI2), TXB2 (stabile metabolite of thromboxane A2) active renin, and arginine vasopressin (AVP) plasma concentrations by radioimmunoassay. Catecholamine levels were assessed by high-pressure liquid chromatography (HPLC) with electrochemical detection. RESULTS: Following MT, arterial hypotension occurred along with a substantial PGI2 release. This was completely abolished by ibuprofen administration. Although plasma levels of 6-keto-PGF1 alpha (1133 (708) vs. 60 (3) ng/L, median (median absolute deviation), P = 0.0001, placebo vs. ibuprofen) remained significantly elevated, blood pressure was restored within 30 min after MT in the placebo group. At the same point in time plasma concentrations of TXB2 (164 (87) vs. 58 (1) ng/L, P = 0.0001), epinephrine (46 (33) vs. 14 (6) ng/L, P = 0.001), AVP (41 +/- (18) vs. 12 (7) ng/L, P = 0.0004), and active renin (27 (12) vs. 12 (4) ng/L, P = 0.001) were significantly higher in placebo-treated patients. CONCLUSION: Under combined general and epidural anesthesia arterial hypotension following MT due to endogenous PGI2 release is associated with enhanced release of AVP, active renin, epinephrine and thromboxane A2, presumably contributing to hemodynamic stability within 30 min after MT.
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.
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