Blood volume determination using hydroxyethyl starch: a rapid and simple intravenous injection method.

OBJECTIVE: To develop and evaluate a new method for blood volume measurements using hydroxyethyl starch as a dilution marker. DESIGN: Laboratory and clinical investigation. SETTING: Neurosurgical operating rooms and anesthesiological laboratories of a university hospital. PATIENTS: Twelve patients who underwent a neurosurgical operation. INTERVENTIONS: Anesthesia and operations were carried out by physicians who were not involved in the study. In addition, blood samples were drawn from 50 volunteers. MEASUREMENTS AND MAIN RESULTS: Blood volume measurements by the hydroxyethyl starch method were validated in vivo by comparison with a conventional carbon monoxide technique. Patients were intravenously injected with hydroxyethyl starch (100 mL) and received simultaneously an injection of carbon monoxide (50 mL) into a closed-circuit ventilation system. Blood samples obtained before and 5 mins after injection were analyzed for carboxyhemoglobin and glucose plasma concentrations after acidic hydrolysis of hydroxyethyl starch. Blood volume was calculated from the difference between glucose concentrations measured after hydrolysis in the plasma, before and after the addition of hydroxyethyl starch. In vitro, the hydroxyethyl starch method had an error and a precision of approximately 2%. In vivo, simultaneous measurements of blood volume using hydroxyethyl starch and carbon monoxide demonstrated a high correlation (r2 = .96, p < .001) between these methods. The mean difference between the two methods relative to their average value was 1.0 +/- 3.5%; the bias was 52.3 mL, and the 95% confidence interval was -64.0 to +168.7 mL. CONCLUSIONS: Blood volume determination by the hydroxyethyl starch method is accurate and rapid and may enhance perioperative monitoring of fluid and blood therapy.

[Advantages and limitations of intraoperative mechanical autotransfusion in al prostatectomies]. / Möglichkeiten und Grenzen der intraoperativen maschinellen Autotransfusion (MAT) bei radikalen Prostatektomien.

UNLABELLED: Intraoperative autotransfusion (MAT), preoperative autologous blood donation, and preoperative normovolaemic haemodilution are three different methods to avoid homologous blood transfusion during surgical procedures. The controversial use of MAT via cell saver in tumour surgery as well as contamination of the operative field with urine illustrate the particular difficulties of autologous blood transfusion in connection with radical prostatectomy. We investigated changes in the osmotic resistance of the retransfused red blood cells (RBC), bacterial contamination, changes in coagulation parameters, and the presence of tumour cells. PATIENTS AND METHODS: After written informed consent, 24 patients who presented for radical prostatectomy were randomly allocated to either a group that used MAT or a group that used homologous transfusion. The patients received "balanced anaesthesia" with midazolam, fentanyl, atracurium, and nitrous oxide/oxygen. The analysed parameters from the preoperative period to the 3rd postoperative day are shown in Table 1. The Haemonetics 3 Plus Cell Saver was used for autotransfusion. RESULTS: Our results showed that the haematologic parameters, coagulation factors, and serum chemistry did not differ between the two groups (Tables 2-4). However, there were significant differences during the investigated period. The osmotic resistance of the salvaged RBCs was higher than that preoperatively. Furthermore, there were no tumour cells in the autologous salvaged RBCs. CONCLUSION: Our results showed no decrease in the quality of the autotransfused RBCs, urine was not retransfused; and there were no significant differences between the groups postoperatively. Although there were no tumour cells in the salvaged blood, the possibility of blood irradiation is discussed. We concluded that because of the risk of infection of homologous blood products, MAT is a safe possibility to reduce the amount of homologous blood transfusion required in connection with radical prostatectomy.

EEG analysis and pharmacodynamic modelling after intravenous bolus injection of eltanolone (pregnanolone).

An intravenous bolus dose of 0.75 mg Kg-1 eltanolone emulsion was administered to 18 unpremedicated ASA I or II patients. In addition to clinical observation and haemodynamic monitoring, EEG power spectrum and median frequency were recorded. Venous blood was collected to establish a concentration-effect relation using the median frequency as a pharmacodynamic parameter for hypnotic effect, and with analysis of data with the sigmoidal Emax model. Emax was determined as the maximal decrease of the median frequency caused by the CNS depressant effect of eltanolone. The results of seven of 15 patients with complete serum and EEG analysis could be described by a sigmoidal curve. The calculated IC50, the serum concentration producing 50% inhibition of Emax, was 0.57 micrograms mL-1. Median frequency occasionally decreased independently of eltanolone serum concentration in seven patients because interference by natural sleep was not prevented before induction or during awakening by setting continuous stimulations. In relation to the peak serum concentration, the decrease in median frequency occurred late in one patient. Nevertheless, the present study provides a preliminary estimation of the IC50 of eltanolone. From the clinical point of view, eltanolone showed satisfactory induction characteristics which warrant further evaluation.

[Intubation conditions and circulatory effects 90 seconds after a divided mivacurium dose with three different TIVA induction methods]. / Intubationsbedingungen und Kreislaufverhalten 90 s nach einer geteilten Mivacuriumdosis bei drei unterschiedlichen TIVA-Einleitungsformen.

UNLABELLED: The aim of this study was to compare the intubating conditions of a mivacurium-induced neuromuscular block 90 s after a divided administration with three different methods of induction of anaesthesia. METHODS: After approval by the local ethics committee, we investigated 36 ASA I and II patients undergoing a 2-h scheduled, elective surgery, in whom a TIVA was induced by one of three different drugs, edomidate, methohexital or propofol. After stable anaesthesia was reached, 0.15 mg/kg and 0.1 mg/kg of mivacurium, spaced 30 s apart, was injected. Endotracheal intubation was performed 90 s after the first micacurium injection and the intubation conditions were graded (1: excellent, 2: good, 3: poor; 4: impossible). The neuromuscular function was stimulated every 20 s by a nerve stimulator in a train-of-four (TOF) pattern, and the time to complete distinction of a TOF response as well as the time of reoccurrence of the first twitch was taken. A minute prior to injection of the relaxant and every minute for 5 min, the systolic and diastolic blood pressure, mean arterial pressure (MAP) and heart rate were measured. The neuromuscular block was maintained with a mivacurium infusion on a level of one twitch response. After cessation of the mivacurium infusion we recorded the time of reappearance of the second, third and fourth twitch responses. RESULTS: All patients could be intubated 90 s after mivacurium except for one, who was excluded for abnormal difficult intubation conditions. The etomidate group had significantly (chi 2 test) worse intubation grades than the methohexital group. In none of the groups did we observe any significant cardiovascular response due to the mivacurium injection, neither in blood pressure nor in heart rate. All groups showed similar onset of the maximal neuromuscular block (4 +/- 1.8 min) and recovery of the first TOF reaction (11.3 +/- 3.4 min). There was no difference in recovery from neuromuscular block maintained by infusion at the end of surgery. CONCLUSIONS: A dose of mivacurium 3.57 times the ED95 does not produce any haemodynamic instability, if it is divided into two parts to induce a TIVA. After this dose, all patients could be safely intubated within 90 s. A prolongation of the neuromuscular block after higher mivacurium doses could not be seen, and this dose did not produce a more rapid onset of the maximal block in any group. The time for recovery from a mivacurium infusion did not differ among the groups. Etomidate, due to its short half-life, seems not ideal for induction of a TIVA together with mivacurium in the dosage used. Mivacurium meets the demands of good controllability as required for a TIVA and can be recommended for a 90-s injection-intubation interval as well as for maintenance of the neuromuscular block.

Effects of chemically defined structured lipid emulsions on reticuloendothelial system function and morphology of liver and lung in a continuous low-dose endotoxin rat model.

BACKGROUND: This study was undertaken to determine the effect of chemically defined structured lipids on nonspecific host defense and on histologic patterns of liver and lungs compared with a physical mixture of long-chain triglycerides and medium-chain triglycerides in a continuous low-dose endotoxin rat model. METHODS: Forty male Sprague-Dawley rats, divided into four feeding groups (structured lipids, structured lipids+endotoxin, physical mixture, physical mixture+endotoxin), received total parenteral nutrition for 48 hours. During the first part of the study, 24 animals were given an injection of live Escherichia coli labeled with radioactive iron (59Fe) to investigate the function of the reticuloendothelial system. During the second part of the study, the liver and lungs of 16 animals were histologically examined using light and electron microscopy. RESULTS: Despite the similar values in the control groups, the animals receiving structured lipids+endotoxin sequestered a significantly greater percentage of bacteria in the liver and spleen (p < or = .01) and a significantly lesser percentage in the lung (p < or = .05) compared with the animals given physical mixture+endotoxin as part of their diet. Moreover, rats in the physical mixture+endotoxin group showed a microscopically evaluated higher fatty infiltration in the liver than did the structured lipids+endotoxin group. CONCLUSIONS: The results of this study indicate that chemically defined structured lipids reduce fatty infiltration of the liver compared with a physical mixture of the same compounds in an animal model of metabolic stress. They were accompanied by a better function of the reticuloendothelial system and a lesser bacterial sequestration in the lungs.

Chemically defined structured lipids with omega-3 fatty acids maintain splanchnic blood flow in a low-dose continuous endotoxin model.

BACKGROUND: Disturbances of microcirculation and accompanying alterations of oxygen supply are central pathophysiological events in trauma and sepsis. There is evidence that omega-3 fatty acids can modulate prostaglandin formation and thereby regional blood flow. The aim of the study was to determine the effects of chemically defined structured lipids (SL) with omega-3 fatty acids in position sn-2 (MFM) compared to SL with omega-6 fatty acids in position sn-2 (MLM) on cardiac output (CO) and splanchnic blood flow in a low-dose endotoxin (E, 1 mg.kgBW-1.day-1) rat model. MATERIALS AND METHODS: 24 male Sprague Dawley rats, divided in 4 groups (n = 6; MLM, MLM+E, MFM, MFM+E) received for 48 h a total parenteral nutrition. CO and regional blood flow were measured with 85strontium-labelled microspheres (16.5 +/- 0.1 microns). RESULTS: There was a slight rise in CO in the E groups compared to the control groups. Application of E resulted in a marked decrease of intestinal perfusion in the MLM-fed animals, whereas the MFM-fed animals showed only a minimal reduction. This decrease of portal blood flow to the liver was accompanied by an elevation of arterial blood flow to the liver. This compensatory increase in arterial liver blood flow was more pronounced in the MFM-fed animals, resulting in a total liver blood flow which was not different from the control group. CONCLUSIONS: The results of this study implicate that 48 h of intravenous feeding with chemically defined SL with an omega-3 fatty acid in position sn-2 can significantly influence splanchnic bed perfusion in a low-dose endotoxin rat model. The better splanchnic perfusion may be mediated by a shift in prostaglandin production.

Induction of nitric oxide synthase activity in phagocytic cells inhibited by tricyclodecan-9-yl-xanthogenate (D609).

1. The synthesis of nitric oxide (NO) by immune-stimulated murine phagocytic cells (J774) and the modulation of this synthesis by tricyclodecan-9-yl-xanthogenate (D609), a specific inhibitor of phosphatidylcholine-specific phospholipase C (PC-PLC), was investigated. D609 dose-dependently suppressed production of NO, as measured by the release of nitrite and nitrate, in response to lipopolysaccharide (LPS) and interferon-gamma (IFN-gamma) in intact cultured cells with an IC50 of approximately 20 micrograms ml-1. D609 at 40 micrograms ml-1 completely abrogated immune-stimulated nitrite production. 2. The inhibitory effects of D609 on nitrite production were time-dependent and restricted to the first 18 h post-stimulation. D609 did not inhibit nitrite production in the cytosol of immune-stimulated phagocytes. 3. These findings indicate that the xanthogenate, D609, is a potent inhibitor of the induction of NO-synthase activity in immune-stimulated phagocytes. Furthermore, since D609 has been demonstrated to inhibit PC-PLC specifically, our findings suggest that the activation of this enzyme by LPS and IFN-gamma is a proximal step in the signal transduction of inducible NO-synthase in phagocytic cells.

Midazolam is metabolized by at least three different cytochrome P450 enzymes.

Distribution volumes and metabolism determine the pharmacokinetics of midazolam. Cytochrome P450 3A4 has been considered a significant enzyme in its metabolism. Using heterologously expressed cytochrome P450 enzymes, we have confirmed the additional involvement of cytochromes P450 3A3 and 3A5 in the hydroxylation of the midazolam. Whereas cytochrome P450 3A3 metabolized midazolam to the same extent as cytochrome P450 3A4, cytochrome P450 3A5 increased its metabolism by a factor of 2.7. The relationship of alpha- to 4-hydroxylation of midazolam was approximately 1.3 for cytochromes P450 3A3 and 3A4, and approximately 8.8 for 3A5. The primary location of cytochromes P450 3A3 and 3A4 is the liver in contrast with cytochrome P450 3A5, which occurs predominantly in the kidney. Therefore, further in vivo study is required to prove conclusively that enzymes in the kidney are involved in the metabolism of midazolam. Nitrendipine itself is metabolized by cytochrome P450 3A enzymes and this was shown to inhibit human liver microsomal hydroxylation of midazolam and preferentially alpha-hydroxylation by about 77%. 4-Hydroxylation was inhibited to 32% of control by nitrendipine. In contrast with inhibition of 4-hydroxylation, alpha-hydroxylation would appear to be competitively inhibited. These findings may be relevant to drug interactions in combined therapy.

Changes in the EEG power spectrum after midazolam anaesthesia combined with racemic or S- (+) ketamine.

Changes in the EEG power spectrum were studied in 50 patients (ASA status I or II), receiving either 2 mg.kg-1 of racemic ketamine or 1 mg.kg-1 of S-(+) ketamine in a randomized and double-blind manner after prior administration of 0.1 mg.kg-1 of midazolam. The patients receiving intramuscular premedication with midazolam about 45 minutes prior to induction of anaesthesia showed, in a deliberately quiet environment and mostly in the early morning, a delta dominated EEG (56% delta power) with a reduced alpha peak (17% alpha power) and an average median of 4 Hz as the baseline findings of the EEG power spectrum. The intravenous administration of midazolam led to activation of the lower beta range (13-18 Hz) and the subsequent injection of ketamine caused an increase in activity in the fast beta range (21-30 Hz), both being accompanied by a reduction of delta power from 56% to 40%. Correspondingly, an increase in the median frequency was noted. Causing nearly the same changes in EEG, S-(+) ketamine was confirmed to be twice as potent as racemic ketamine.

[Neuromonitoring in carotid surgery: possibilities and limits of transcranial Doppler ultrasound]. / Neuromonitoring in der Karotischirurgie: Möglichkeiten und Grenzen der transkraniellen Doppler-Sonographie.

In order to evaluate the suitability of transcranial Doppler sonography as an intraoperative monitor in carotid surgery, we compared measurements of mean blood flow velocity in the ipsilateral middle cerebral artery with the cortical response of somatosensory evoked potentials in a prospective study of 176 carotid operations. SEP recording was readily feasible during all procedures and by means of SEP loss all patients at risk for critical cross-clamp related cerebral ischemia were reliably identified. In contrast, TCD could not be used for assessment of cerebral hemodynamics in more than 40% of patients. What is more, in high risk patients with intraoperative loss of SEP, TCD could not be performed in 74% of cases. This high rate of failure limits the usefulness of TCD as an intraoperative monitor and detracts from the additional benefit of identifying cerebral embolism and hyperperfusion as potential causes of neurological deficits. In contrast to SEP recording, TCD cannot be recommended as a routine monitor in carotid surgery.

[The risk of anesthesia in bronchopulmonary diseases]. / Das Anästhesierisiko bei bronchopulmonalen Erkrankungen.

Surgery and anaesthesia, including positioning and mechanical ventilation, encompass alterations in respiratory mechanics and gas exchange persisting through the postoperative period and may cause respiratory complications. The closer the anatomical ties between the surgical site and the respiratory system, the higher the pulmonary risks. Pre-existing respiratory and pulmonary diseases further increase the patient's risk. In addition to the numerous patients suffering from chronic obstructive pulmonary disease, patients with restrictive disorders, e.g. obesity, are concerned as well. Arterial oxygen saturation tracked by pulse oximetry is recommended for screening the respiratory system. Patients at an increased risk of respiratory complications should be scheduled individually for preoperative preparation, anaesthesia requirements, and postoperative management. When anaesthetizing patients with coexisting pulmonary disease, regional anaesthesia is preferred unless limited by the surgical procedure or for obvious technical reasons. Pasch provides recommendations for the management of anesthesia: Acute respiratory obstruction should be prevented by personal attention and pharmacological protection. Anaesthetics and relaxants with parasympathomimetic and histamine liberating effects should be avoided. Attention should be paid to hazardous pharmacological interactions with existing respiratory therapy. Bronchospasm should be avoided by deep anaesthesia and by smooth intubation and extubation. Pain therapy is an essential requirement for respiratory therapy in the postoperative period to maintain or to restore pulmonary function with improved performance.

Increased fMet-Leu-Phe receptor expression and altered superoxide production of neutrophil granulocytes in septic and posttraumatic patients.

Activation of neutrophils by various inflammatory stimuli has been shown to play a pivotal role in septic and posttraumatic tissue injury. To further elucidate the mechanisms modulating the oxidative metabolism, we assessed superoxide production induced by N-formylmethionyl-leucyl-phenylalanine (FMLP) and phorbol myristate acetate and the expression of FMLP receptors of human neutrophils on several days during sepsis and after trauma. Neutrophils of septic patients isolated on days 0-4 after the diagnosis of sepsis showed a significant, more than twofold increase in specific binding of [3H]FMLP at 1, 120, and 240 nM. Scatchard plot analyses revealed that this increase in specific binding was due to an increase in the number of low- and high-affinity FMLP receptors with no changes in receptor affinity. On days 5-10 after the onset of sepsis the up-regulation of FMLP receptors on circulating neutrophils was followed by receptor down-regulation. Likewise, neutrophils from patients with trauma that was not complicated by sepsis bound significantly more [3H]FMLP than neutrophils from volunteers. However, the increase in FMLP receptors was less than that in septic neutrophils and returned earlier to normal. In accordance with the up-regulation of FMLP receptors, neutrophils obtained from patients with sepsis or after trauma on days 1-4 and days 1-2, respectively, produced significantly more superoxide anion upon stimulation with FMLP. However, after stimulation with phorbol myristate acetate, a receptor-independent activator of protein kinase C, these cells released less superoxide anion than controls.(ABSTRACT TRUNCATED AT 250 WORDS)

[Induction of anesthesia using the new intravenous steroid anesthetic eltanolone (pregnanolone). Dose determination and pharmacodynamics]. / Narkoseeinleitung mit dem neuen intravenösen Steroidanästhetikum Eltanolon (Pregnanolon). Dosisfindung und Pharmakodynamik.

Since the 1940s several preclinical investigations have demonstrated the anaesthetic activity of a series of structurally related pregnanes without notable endocrine action. One of the most active of these is pregnanolone (3-alpha-hydroxy-5-beta-pregnane-20-one), which is a naturally occurring metabolite of progesterone. Pregnanolone is not soluble in water, which has prevented its use for clinical research. In 1987, however, a stable oil-in-water emulsion of eltanolone that could be used for i.v. administration in man was introduced by KABI Pharmacia, Stockholm, Sweden. METHODS. In an open study the dose of eltanolone that induces anaesthesia in 50% of the patients (AD50) was estimated according to the "up and down method" of Dixon and Massey. Respiratory and cardiovascular effects were evaluated as well as the reliability of eltanolone emulsion. The study was conducted in accordance with the Declaration of Helsinki and started after the approval of the local Medical Ethics Review Committee. In all, 31 patients of ASA risk categories I and II (male or female with non child-bearing potential) were included in the study after written informed consent had been obtained. All patients were premedicated with 5 mg midazolam i.m. about 30 min before the injection of eltanolone. Eltanolone emulsion was given i.v., usually on the back of the hand, over 20 s. In connection with the injection of eltanolone every patient was asked whether he or she felt any pain or discomfort at the injection site. As suggested by results in volunteers in a previous study the starting dose was 0.5 mg/kg body weight. Cessation of counting and loss of eyelash reflex were used as indicators of efficacy in the induction of anaesthesia. If these criteria were achieved within 120 s after the start of injection (responder) the dose for the next patient was decreased by 15%, if not (non-responder), the next patient received the same dose plus 15% (up to 1.01 mg/kg body weight). Heart rate and oxygen saturation were recorded continuously (Sirecust 404; Nellcor) from 1 min before to 10 min after the start of injection, and blood pressure was measured noninvasively 1 min before induction and then at 1, 2, 3, 5, 8 and 10 min from the start of the eltanolone injection (Sirecust 888). If oxygen saturation fell to 85% oxygen was applied by way of the face mask and the patients were ventilated if necessary. Respiratory disturbances, time to and duration of apnoea were recorded, as were involuntary movements or increase in muscle tone. Usually intubation was carried out at the end of the 10-min observation period using thiopentone, vecuronium and suxamethonium. If a patient did not fall asleep or awoke prematurely, intubation was performed in the same way and from this point pharmacodynamic parameters were no longer evaluated for the study. RESULTS. The AD50 was 0.33 mg/kg body weight, and the 95% confidence interval, 0.30-0.36 mg/kg body weight. The eltanolone dose varied from 0.25 to 0.5 mg/kg body weight. Induction was successful in 17 (of 31) patients according to the eyelash reflex as criterion and in 28 according to cessation of counting. Above 0.38 mg/kg body weight efficacy variables were achieved in all patients, while below 0.29 mg/kg body weight eyelash reflex was not lost in any patient. The mean time to loss of consciousness (cessation of counting) in the responder group was 48 +/- 12 s after the start of injection and loss of eyelash reflex was recorded after 94 +/- 13 s. In the nonresponder group eyelash reflex persisted over 120 s in all patients and counting stopped on average after 72 +/- 23 s. Three patients in this group also did not stop counting (dose: 0.29 mg/kg body weight). Blood pressure remained stable in all patients but 1 throughout the observation period. In 1 patient there was an alarming rise in blood pressure from 160/90 mmHg before to 200/100 mmHg 3 min after the injection.(ABSTRACT TRUNCATED AT 400 WORDS)

Anesthesia training in West Germany.

The specialty of anesthesia was established in German medicine in 1953 with the founding of the Germany Society of Anaesthesia and the inclusion of a "specialist in anesthesia" as part of the German medical training requirements. Anesthesia training is offered to students and residents and as a part of continuing education. A residency training program lasts at least 4 years, including 6 months of intensive care unit (ICU) training, and ends with an oral examination. About 900 anesthesia departments in West Germany are accredited for residency training programs. Of those, about 320 are fully accredited. Continuing education in West German anesthesia is very similar to that offered in the United States.

[Artificial feeding]. / Künstliche Ernährung.

An infusion rate above 3 g/kg BW per day glucose leads to a reduction of oxidative metabolism of the energy sources glucose, free fatty acids, and exogenous triglycerides. Simultaneously splanchnic lipogenesis is stimulated and visceral protein utilization inhibited. During the 1st to 4th day after trauma Xylitol (3 g/kg BW per day) is superior to glucose with regard to oxidative metabolism of energy sources and stimulation of visceral protein synthesis. A comparable metabolic effect can be achieved by a glucose/xylitol mixture (1:1); (6 g/kg BW per day) during long-term nutrition.

[Long-term intubation and tracheotomy]. / Langzeitintubation und Tracheotomie.

Benefits and disadvantages of long-term nasal and oral endotracheal intubations vs. tracheotomy are discussed. The incidence and severity of complications is higher following prolonged endotracheal intubation than tracheotomy. Laryngeal injury is more serious than tracheal. Tracheotomy therefore is advantageous in all patients requiring long-term ventilatory support. The optimal timing for tracheotomy is ranging from 48 to 120 hours following endotracheal intubation. Tracheal stenosis secondary to trachestomy depends on tracheal wall perfusion. The risk of tracheal stenosis may be minimized by diligent performance of tracheostomy, and by sewing the trachea to the skin, and by using solidly fixed tracheal cannulas with high-volume low-pressure cuffs.