HES 130/0.42 shows less alteration of pharmacokinetics than HES 200/0.5 when dosed repeatedly.

BACKGROUND: Hydroxyethyl starches (HES) accumulate in the circulation when administered repeatedly. Accumulation is thought to be partly responsible for undesirable effects (tissue storage, blood coagulation impairment, and itching). HES 130/0.42 with low molecular weight and a low level of substitution has recently been developed in order to reduce those risks. METHODS: In healthy volunteers, the pharmacokinetics of HES 130/0.42/6:1 were investigated using a crossover design with HES 200/0.5 serving as control. Fifty grams of either HES were administered in 4 h day-1 for a period of five consecutive days. HES serum concentrations were used for computation of pharmacokinetic coefficients. Change between the first and fifth infusion in the area under the concentration curve (AUC) served as the primary measurement. RESULTS: Although the circulation was freed from the load with HES 130/0.42 within 20 h after end of the previous infusion, the amount of HES 200/0.5 increased continuously from one administration to the other. AUC and elimination half-life (t1/2) were significantly lower with HES 130/0.42. AUC and t1/2 of HES 200/0.5 showed an increase between the first and the fifth administration whereas only a minimal shift was present with HES 130/0.42. Haemodilution via HES 200/0.5 did not change over time. CONCLUSIONS: Repeated administration of HES 130/0.42 shows no accumulation and fewer tendencies to time-dependent changes in pharmacokinetic parameters than HES 200/0.5. The improved reproducibility may improve drug safety, particularly as the accumulation of residual starch with HES 200/0.5 does not contribute to the colloid's volume effect, but may rather increase the risk of undesired reactions.

[Severe adverse event following iv administration of 10 ml 6% Dextran60 (0.6 g) in a healthy volunteer]. / Schwerer Zwischenfall nach i.v.-Applikation von 10 ml (0,6 g) 6%igem Dextran60 bei einem gesunden Probanden.

We describe the case of a 24-year-old healthy volunteer who underwent a dextran-induced anaphylactic/anaphylactoid reaction (DIAR) type III after administration of 10 ml 6% Dextran60 (0.6 g) during a preliminary examination. There were no specific incidents in the medical history or any infusions of any colloids. In contrary to other DIAR case reports of anaphylactic reactions, in this case we observed a latency period after intravenous application of Dextran60 to the first clinical symptoms of anaphylactic shock of about 5 min. The initial decrease of systolic blood pressure to less than 90 mmHg and consecutive increase in heart rate to higher than 90 bpm returned to normal after therapy with head-down position, iv injection of 2 mg Clemastin, 100 mg hydrocortisone and infusion of 500 ml hydroxyethyl starch after approximately 8 min. During this period responsiveness was unsatisfactorily although the volunteer complained about warming of the skin, paresthesia and nausea. Immediate shock symptoms that normally belong to antigen-antibody reactions were not observed. It is therefore still unclear whether this case was caused by antibody reactions. Nevertheless, to provide DIAR it is still absolute necessary to give 20 ml Promit((R)) 15% in advance. It is not an acceptable alternative to infuse the first 100 ml of dextran as a bolus and it must remain a point of discussion as to whether the reactions described could have been due to a bolus administration of the first 100 ml Dextran. It is absolutely necessary to accurately monitor the first 10 min after an infusion even if only small volumes of dextran (i.e. 0.6 g) are infused. This is becoming more and more important due to the increasing use of "small volume resuscitation", solutions containing dextran (RescueFlow((R)), Biophausia AB, Uppsala, Schweden) or cryoconservation with dextran.

[Wound management with coconut oil in Indonesian folk medicine]. / Uber die Wundbehandlung mit Kokosöl bei indonesischen Naturvölkern.

The medical plants which are used to treat wounds and injuries by the ethnic group of Ngada on Flores, an Eastern Indonesian island, will be presented. Additionally, the coconut oil used to treat wounds and to conserve medicinal plants will be analysed biochemically. The people of Ngada use the following plants for wound treatment: seeds of the betel nut (Areca catechu L.), fruits of papaya (Carica papaya L.), leaves of the Indian Hydrocotyle (Centelle asiatica L.), the rhizome of turmeric (Curcuma domestica Val. and Curcumara xanthorrhiza Roxb.), leaves of betel (Piper betel L.). Coconut oil is particularly useful because of its biochemical structure: unlike olive oil and animal fatty tissue, it consists of short-chained and saturated fatty acids. These qualities in coconut oil prevent it from becoming oxidized and rancid, thus making it suitable for the preservation of medicinal plants and for wound treatment.

[Thrombelastographic coagulation analysis following in vitro and in vivo haemodilution with hydroxyethyl starch (HES)]. / Thrombelastographische Gerinnungsanalyse nach in-vitro- und in-vivo-Hämodilution mit Hydroxyethylstärke (HES).

In the study presented the effects of in vitro hemodilution with HES on coagulation are compared with the effects of in vivo hemodilution using thrombelastography (TEG). The in vivo hemodilution was performed by the i. v. infusion of 1000 ml 6 % solution of hydroxyethyl starch HES (2 formulations with HES 130/0.4 and one formulation with HES 200/0.5) in healthy volunteers during 30 min. The in vitro hemodilution was performed with blood samples taken from the volunteers before the infusion was started. These samples were diluted with HES-solution until the same hemoglobin concentration measured at the end of the infusion was attained. The in vivo TEG-parameters remained in the reference range of the method, however all in vitro TEG-parameters are out of the range of normal values. The isolated interpretation of the in vitro data shows an impairment of blood coagulation. The shortening of the reaction time as an indicator for the initiation of blood clotting points to activated coagulation by in vivo hemodilution with HES, whereas in vitro the prolongation of the reaction time is indicative for retardation of clotting. The evaluation of the TEG-parameters and of other clotting parameters determined prior to the beginning of the infusion, at the end of the infusion and four hours after termination of the infusion of HES 130/0.4 and of HES 200/0.5 to healthy volunteers show alterations of blood coagulation parameters caused mainly by dilutional effects. The more pronounced alterations found in vitro cannot be interpreted as impairment of haemostasis in vivo. On the other hand, the likewise haemodilution in vitro causes an impairment of coagulation. Therefore, the effects of in vitro hemodilution with HES on coagulation differ qualitatively and quantitatively from the effects of in vivo hemodilution.

[The in vivo molecular weight and renal threshold of hydroxyethyl starch in the example of molar substituted HES70/0/5]. / Das in vivo mittlere Molekulargewicht und die Nierenschwelle von Hydroxyethylstärke am Beispiel mittelsubstituierter HES (HES 70/0,5).

The intravascular changes of the in vivo molecular weight of HES 70/0.5 were investigated on healthy volunteers. A repeated daily infusion of 835 ml of 6% HES solution (50 g HES 70/0.5; Rheohes) during four hours on five consecutive days was performed. The analysis of the distribution of the molecular masses in serum and urine was performed by SEC-HPLC with MALLS/RI detection. The in vivo average molecular weight (Mw) of HES was found to be 58,000 Da at the end of the infusion. This was lower than the Mw of 66,000 Da as measured initially in the HES solution. In the time following the infusion Mw increased steadily up to 64,000 Da because of renal elimination of low molecular HES. However, in the morning before the start of the next infusion of HES, the average molecular weight Mw of HES was even higher up to 71,000 Da. In the first collected portion of urine (i.e. up to 8 h after beginning the infusion) the average molecular weight of HES was as low as 17,000 Da. During the next hours (i.e. in the second collection period lasting from 8 up to 24 h after start of the HES infusion) Mw of HES increased up to 28,000 Da. The top fraction of the first period showed molecular masses of 27,000 Da, in the second collection period top fraction of molecular masses measured 40,000 Da. According to the presented data it is concluded that the renal threshold for medium substituted HES is independent of the initial Mw and related primarily to the molar substitution of the HES used. This renal threshold for medium substituted HES is determined to be at 40,000 Da. The in vivo Mw of HES is variable and related to the sampling time and predicted predominantly by the molar substitution of the HES used. The in vivo Mw, therefore, is not suited for characterisation of HES.

[Acetyl starch as volume substitute, a possible alternative to HES]. / Acetylstärke als Volumenersatz, eine mögliche Alternative zu HES.

OBJECTIVES: Pharmacokinetics and tolerability of acetyl starch (ACS) in comparison to hydroxyethyl starch (HES) were investigated after repeated intravenous infusions. METHODS AND COHORTS: A 500 ml solution of ACS (n = 8) or HES (n = 9) was infused to male volunteers (Age 25-42 Years) over four hours on five consecutive days. RESULTS: Comparing the pharmacokinetic parameters, marked differences were found between ACS and HES. A continuos increase of Cmax, AUC0-24 and t1/2 over the five days caused by administration of HES was due to an accumulation of HES in serum. However, after administration of ACS all these parameters remained unaltered. The repeated infusion of 50 g ACS did not cause any changes of the acid-base-status. The influence of ACS on the coagulation parameters was comparable to that of HES and due to dilution effects. The acetic acid concentration increased up to 2.96 +/- 0.67 mg/dl following ACS infusion. The blood glucose concentration was not influenced by the infusion of HES or of ACS. The repeated ACS infusions were well tolerated. In contrast to HES, ACS did not accumulate in serum. CONCLUSION: According to these data ACS is an alternative to HES for volume replacement. Well-known side effects due to long storage of HES in tissues may not occur following application of ACS. However, the wide usage of ACS is restricted by the limited stability of ACS solutions at room temperature. ACS solutions are thus only stable during storage at lower temperatures.

Pharmacodynamics and tolerability of acetyl starch as a new plasma volume expander in patients undergoing elective surgery.

OBJECTIVE: Acetyl starch (ACS) is a new synthetic colloid solution for plasma volume expansion and is now undergoing phase II clinical trials. We compared the pharmacodynamics and tolerability of ACS with those ofhydroxyethyl starch (HES) in 32 patients (American Society of Anesthesiologists physical status I and II) undergoing elective surgery. SUBJECTS, MATERIAL AND METHODS: In this prospective, randomized, double-blind trial patients received either 15 ml/kg ACS 6% (average molecular weight (Mw) 200,000/molar substitution (MS) 0.5) or HES 6% (Mw 200,000/MS 0.5) i.v. up to a maximum dose of 1000 ml. Hemodynamic parameters, rheologic parameters, volume effect, acid-base status as well as effects on hemostasis were studied. RESULTS: After infusion of ACS and HES there was a similar increase in central venous pressure and mean arterial pressure in both groups. Acid-base status was not significantly altered after the end of the colloid infusions. After ACS infusion, plasma acetate concentration increased from 0.13+/-0.16 mg/dl to 2.87+/-1.13 mg/dl, however, after 24 h there was no significant difference in plasma acetate concentration compared to HES. The volume effect ranged from 104-116%(ACS) and from 88-118% (HES) of the colloid dose administered. These differences were not statistically significant. Partial thromboplastin time (aPTT) was only slightly increased after ACS infusion (from 38.6+/-5.7 sec to 41.4+/-5.1 sec), but was significantly increased after HES infusion (from 38.7+/-5.7 sec to 46.1+/-7.0 sec). CONCLUSION: ACS and HES are equally effective plasma volume expanders; ACS might be a new, alternative colloid solution with fewer coagulation side-effects than HES.

[The use of lithium hydroxide for carbon dioxide absorption prevents formation of compound A during sevoflurane anesthesia]. / Die Anwendung von Lithiumhydroxid als Kohlendioxidabsorbens verhindert das Entstehen von Compound A während Sevoflurananästhesie.

UNLABELLED: Aim of the study was the clinical investigation of sevoflurane degradation when using water-free lithiumhydroxide versus moist Drägersorb 800 for carbon dioxide absorption. METHODS: Concentrations of Compound A in the inspiratory gas mix and serum fluoride levels were measured in two groups of 8 patients each. RESULTS: When water-free lithiumhydroxide was used for carbon dioxide absorption, concentration of Compound A in the inspiratory gas mix was ca. 1 ppm (near minimal level of detection) as compared to ca. 20 ppm for moist Drägersorb 800. The concentration of fluoride increased during sevoflurane anesthesia (15.0 +/- 4.8 mumol/l with lithiumhydroxide versus 21.9 +/- 4.0 mumol/l with Drägersorb 800 after 60 mins). CONCLUSIONS: When lithiumhydroxide is used, there is only minimal formation of compound A from sevoflurane degradation. Since serum fluoride levels increased in both patient groups, we conclude that this is caused mainly by metabolism of sevoflurane. Capacity of lithiumhydroxide for carbon dioxide absorption is similar to that of Drägersorb 800. Therefore, the use of lithiumhydroxide increases patient safety.

[The accumulation of different substituted hydroxyethyl starches (HES) following repeated infusions in healthy volunteers]. / Zur Kumulation unterschiedlich substituierter Hydroxyethylstärke (HES) nach repetitiver Infusion bei gesunden Versuchspersonen.

AIM OF THE STUDY: Accumulation of hydroxyethyl starch (HES) after repeated applications of starches with different molar substitution and similar molecular weight was investigated. METHODS: Treatment with five consecutive infusions of hydroxyethyl starch was carried out using two medium molecular weight hydroxyethyl starches with a molar substitution of 0.5 and 0.62. Healthy volunteers received 500 ml 6% HES 200/0.62 (30 g) or 500 ml 10% HES 200/0.5 per day over a period of five consecutive days. Blood samples were taken in the morning before infusions were started (7.A.M.) and at each hour during the infusion period of 4 hours post infusionem until 4 hours after the infusions. During the first 10 days and on the 20th and on the 30th day after the last infusion blood samples were taken. RESULTS: Both HES solutions were subjectively and objectively well tolerated by healthy volunteers. No side effects were observed. However, pharmacokinetics of the investigated HES-formulations were significantly different. The model-independent calculated elimination half life time (T1/2) increased from day to day. During the five days T1/2 was prolonged for 20 h by high substituted HES (200/0.62) and for 2.5 h for medium substituted HES (200/0.5). The half life times related to the three compartment model calculation were with 0.6 h, 11.6 h and 211 h for HES 200/0.62 two fold higher than the times for HES 200/0.5 with 0.39 h, 6.98 h and 113 h. Plasma clearance for HES 200/0.5 (4.86 ml/min) was five fold higher than that from HES 200/0.62 with 0.98 ml/min. With the exception of the first day of infusion serum concentrations of HES 200/0.5 although only 30 g HES 200/0.6 versus 50 g HES 200/0.5 were infused. No difference of the hemodilution effects between the two HES-formulations were observed. The hemorheologic parameters were similar in both groups with the exception of plasma viscosity which was significantly higher after infusion of HES 200/0.62. CONCLUSION: High substituted HES accumulate in serum more than medium substituted HES. Especially when HES must be applied in multiple doses, high substituted HES should not be used or the infusion interval must be adapted to the elimination half life time of the used HES.

Lipid and lipoprotein profiles in children with familial hypercholesterolaemia: effects of therapy.

UNLABELLED: In 71 children with familial hypercholesterolaemia the effect of dietary and/or medical treatment was evaluated. Initial total cholesterol and low density lipoprotein (LDL)-cholesterol levels were significantly lower in children who were consecutively treated by diet (Step-One-Diet) than in those who received additional medication. By dietary treatment, the median total cholesterol level (236.5 mg/dl; range 210-510 mg/dl) was reduced by 7.4% and the median LDL-cholesterol level (162 mg/dl; range 126-423 mg/dl) by 9.9%. By dietary and medical therapy, the median total cholesterol level (330 mg/dl; range 270-424 mg/dl) was reduced by 29.7% and the median LDL-cholesterol level (263 mg/dl; 192-333 mg/dl) by 25.9%. High density lipoprotein (HDL)-cholesterol and HDL 3 remained unchanged. HDL 2 showed a significant decrease of 15.6% up to 27 mg/dl (13-42 mg/dl) on medical treatment. Apolipoprotein A I levels did not change during therapy. Initial apolipoprotein B levels were significantly higher in children who were treated by diet and medication and were reduced by 28.9% by combined therapy. In 28 patients (39.4%) an excess of lipoprotein (a) was detected. Regarding the apolipoprotein E phenotype, 32.2% of the patients carried the risk gene epsilon4 in a hetero- or homozygous form. CONCLUSION: Early dietary and/or medical treatment in hypercholesterolaemic children significantly ameliorates the lipoprotein status. The pretherapy lipoprotein status seems to prognosticate the effectiveness of therapy.

The pharmacokinetics of acetyl starch as a plasma volume expander in patients undergoing elective surgery.

UNLABELLED: Acetyl starch (ACS) is a new synthetic colloid solution for plasma volume expansion and is now undergoing phase 2 clinical trials. We compared the pharmacokinetics of ACS with those of hydroxyethyl starch (HES) in 32 patients (ASA physical status I and II) undergoing elective surgery. In this randomized, double-blind trial, patients received either 15 mL/kg ACS 6% (average molecular weight [Mw] 200,000/molar substitution [MS] 0.5) or HES 6% (Mw 200,000/MS 0.5) i.v. up to a maximal dose of 1000 mL. Plasma colloid concentrations were measured by repetitive arterial blood sampling over 24.5 h. Plasma colloid concentrations were detected using a high-pressure liquid chromatography controlled enzymatic test. Standard pharmacokinetics were calculated, including initial half-life (t(1/2init)), i.e., the time required for a 50% decline of the maximal plasma colloid concentration at the end of drug infusion. Whereas HES was eliminated by second-order kinetics, ACS followed first-order characteristics. In the first hours after i.v. administration, t(1/2init) and clearances were similar in both groups. However, the terminal half-life of HES was significantly longer than that of ACS (9.29 +/- 1.43 h vs 4.37 +/- 1.06 h). After 16.5 and 24.5 h, ACS showed significantly lower plasma concentrations than HES, which indicates that the final degradation of ACS by esterases and amylase was significantly more rapid. ACS might be an alternative plasma volume expander, which avoids the accumulation of persisting macromolecules. IMPLICATIONS: We studied the pharmacokinetics of acetyl starch, a newly developed colloid solution for plasma volume substitution, compared with hydroxyethyl starch in 32 surgical patients undergoing elective major general surgical procedures. In contrast to hydroxyethyl starch, this new agent undergoes rapid and nearly complete enzymatic degradation.

[Various reactions of sevoflurane with the individual components of soda lime]. / Unterschiedliche Reaktion von Sevofluran mit einzelnen Komponenten von Atemkalk.

The various components of commercial soda lime (sodium hydroxide, potassium hydroxide, calcium hydroxide, barium hydroxide) were studied in terms of their reactivity with sevoflurane at its boiling point (59 degrees C). A simple closed system, a reflux cooler, served as a model. Analyses were performed by GC/MS. Besides sevoflurane, we identified four compounds: A, B, C, and D. Free methanol, formaldehyde and formic acid could not be found. Presumably methanol is transferred from an intermediate formalin-semiacetal of the hexafluorisopropanol. Calcium hydroxide and barium hydroxide showed little reaction with sevoflurane, whereas larger amounts of reaction products were observed with sodium hydroxide and potassium hydroxide. The alkali hydroxides of sodalime are presumably responsible for its reaction with halogenated inhalation anaesthetics. We therefore conclude that decomposing reactions of halogenated inhalation anesthetics with dry soda lime could be prevented by using a newly developed soda lime.

[Addition of fentanyl to bupivacaine--peridural analgesia in cesarean section]. / Zusatz von Fentanyl zur Bupivacain--Periduralanalgesie bei Sectio Caesarea.

UNLABELLED: Epidural anaesthesia for elective caesarean section can have advantages over general anaesthesia. The anaesthesiologist can avoid endotracheal intubation as well as fetal depression following placental transfer of systemic anaesthetics. However, despite reaching an effective blockade preoperatively, intraoperative discomfort and pain may occur during epidural anaesthesia with local anaesthetics alone, necessitating supplemental systemic analgesics or even conversion to general anaesthesia [21]. Addition of epidural fentanyl has been shown to improve onset and quality of perioperative analgesia without evident side effects for mother or newborn [24]. Nevertheless, administration of epidural opioids before cord clamping is still hotly debated, some fearing maternal and or neonatal depression [6, 26]. The aim of the present study was to investigate the quality of analgesia, associated side effects and the resulting maternal and neonatal plasma opiate concentrations after a single preoperative addition of 0.1 mg fentanyl to epidural bupivacaine analgesia in comparison to epidural bupivacaine analgesia alone. METHODS: Following governmental and ethics committee approval, 43 elective consenting patients for caesarean section were randomized to receive double-blind injections of either 8 ml 0.5% bupivacaine(+)0.1 mg fentanyl (B+F group, n = 22) or 8 ml 0.5% bupivacaine +2 ml saline (Bup group, n = 21) into an epidural catheter. In both groups additional injections of bupivacaine were given to achieve sensory blockade up to T4. Systolic blood pressure, heart and respiratory rates were measured regularly. Quality of intraoperative pain relief was assessed at delivery, uterine eventration, and during uterine and abdominal closure using a visual analogue scale (VAS). The duration of postoperative analgesia was compared between groups, as well as the incidence of nausea, itching or sedation. Similarly, Apgar scores and umbilical arterial and venous blood gas analyses were compared. Fentanyl concentrations were determined in maternal venous blood sampled before and 20 and 40 min after epidural injection and at birth, and in umbilical venous and arterial blood sampled after delivery. Radioimmunoassay analysis was performed from plasma specimens centrifuged and frozen at -20 degrees C [19]. The statistical level of significance was defined as P < 0.05. RESULTS: Groups were comparable regarding age, weight and time of gestation. Total bupivacaine doses and injection to delivery times were similar in both groups. Figure 1 shows that there were 40% more pain-free (VAS = 0) patients in the B+F group during uterine eventration and wound closure (P < 0.05). Mean postoperative duration of analgesia was significantly longer in the B+F group (382 vs 236 min). The rate of nausea and mild itching was significantly higher in the B+F group. Respiratory depression was never detected in patients or newborns. Small group differences in blood pressure or respiratory rate were inconstant and clinically irrelevant, as were differences in umbilical venous pCO2. One hundred and twenty-five blood samples were analysed for fentanyl concentrations. The mean fentanyl concentration before epidural injection was not zero, but 0.25 ng/mg (range 0.02-0.32). Maternal concentrations at 20 and 40 min after injection were 0.55 ng/ml (0.12-1.14) and 0.52 ng/ ml (0.26-1.04) (Fig. 3). At delivery, mean maternal fentanyl concentration was 0.58 ng/ml (0.14-1.18); mean umbilical arterial and venous concentrations were 0.51 ng/ml (0.04-1.8) and 0.41 ng/ml (0.18- 1.2), respectively. Rare results of fentanyl concentrations > 1.0 ng/ml correlated neither with sedation, maternal respiratory rate and side effects, nor with Apgar scores and umbilical blood gas values. No Apgar score at 5 min was below 9, and no umbilical pH was below 7.20. (ABSTRACT TRUNCATED)

[Repeated addition of fentanyl to bupivacaine peridural analgesia in labor. Clinical action and fentanyl plasma level]. / Wiederholter Zusatz von Fentanyl zur peripartalen Bupivacain-Periduralanalgesie. Klinische Wirkung und Fentanyl-Plasmaspiegel.

A combination of epidural opioids with local anaesthetics has been used to improve pain relief during labor and to reduce side effects, such as muscle weakness, usually seen when local anaesthetics are used alone. The addition of epidural fentanyl (F) produces highly effective analgesia, the only side effect being mild itching. Initial trials investigated the improvement in analgesia after a single administration of F during first- but not during second-stage labor. Even though pain perception during second-stage labor under epidural analgesia with local anaesthetics can be severe, the addition of opioids was avoided for fear of neonatal or maternal depression. A recent report found maternal and umbilical plasma concentrations following injection of 100 micrograms F to be safe and the investigators speculated that repeated addition of epidural/F to injection of local anaesthetic may prove beneficial for the parturient without exposing the mother or fetus to risk. We therefore studied maternal analgesia, maternal and umbilical plasma levels and associated side effects following repeated addition of 100 micrograms F to bupivacaine epidural analgesia during labor. METHODS. Following institutional and governmental approval 53 parturients were randomly assigned to receive either 8 ml bupivacaine 0.25% + 0.1 mg fentanyl (B + F group; n = 28) or 8 ml bupivacaine 0.25% + 2 ml saline (BUP group; n = 25) in an epidural catheter at L2/3. The same dose was reinjected upon the patients' request regardless of the degree of cervical dilatation. Blood pressure, heart rate, respiratory rate and the incidence of side effects were recorded before and following each epidural injection. Pain relief was determined at each injection and following cord clamping using the visual analogue pain scale (VAS; 0-100 mm). Maternal venous blood samples were collected to measure plasma F concentrations before and 20 and 40 min after each injection and at birth when umbilical venous and arterial blood was obtained. After centrifugation the samples were maintained at -20 degrees C and then analyzed by radioimmunoassay. At delivery, Apgar scores and umbilical venous and arterial blood gas values were determined. RESULTS. Both groups were comparable for age, weight, height, gestational age and parity. A total of 48 epidural injections were evaluated in the B + F group, 43 in the BUP group. No statistically significant group difference was found between the frequency of injections per delivery (B + F: 2.2; BUP: 1.8); regarding the time between the initial and the first top-up dose (B + F: 144 min; BUP: 140 min) or regarding the interval between the last injection and birth (B + F: 94 min; BUP; 90 min). However, the quality of pain relief during labor and particularly at birth was significantly improved by F (mean VAS in B + F group: 6 mm; mean VAS in BUP group: 42 mm). Mild itching was observed in 43% of patients receiving F, moderate shivering in 13% versus 40% in patients not receiving F. At control mean maternal F plasma levels were not zero but 0.25 ng/ml. After the initial injection and following the first and second top-up dose mean maximum maternal F plasma concentrations were 0.54 ng/ml (+/-0.32; +/-SD), 0.88 ng/ml (+/-0.62) and 1.06 ng/ml (+/-0.4) (range 0.18-2.76 ng/ml), respectively. The increase in maternal F concentrations with increasing injection frequency was statistically significant (P < 0.02). Mean umbilical venous and arterial F concentrations at birth were 0.72 ng/ml (+/-1.16) and 0.62 ng/ml (+/-0.52). No significant group differences were found regarding Apgar scores or umbilical blood gas analyses. In one newborn, radioimmunoassay resulted in unexplainably high umbilical F concentrations without any clinical signs of sedation, depressed vigilance and without any sequellae. DISCUSSION. Repeated addition of 100 micrograms F to epidural anaesthesia with bupivacaine significantly improves analgesia and provides pain relief not only during the fir

Midazolam does not antagonize fentanyl-mediated analgesia in surgical patients.

STUDY OBJECTIVE: To determine whether midazolam possesses a clinically significant antianalgesic action in surgical patients. DESIGN: Randomized, controlled study. SETTING: Inpatient anesthesia at a university department of neurosurgery. PATIENTS: 2 groups of 10 patients each who were scheduled for supratentorial brain surgery, did not have elevated intracranial pressure, and were free from systemic disease. INTERVENTIONS: Patients underwent anesthesia induction with hexobarbital, succinylcholine, and pancuronium; anesthesia was maintained with injections of droperidol-fentanyl (Group 1) or with midazolam-fentanyl (Group 2) following a predetermined repetitive dosing schedule, such that fentanyl 0.1 mg was injected upon predominant increases in heart rate, whereas droperidol 2.5 mg or midazolam 2.5 mg was injected upon increases in blood pressure. MEASUREMENTS AND MAIN RESULTS: Duration of anesthesia and invasiveness of surgery were similar in both groups. The amount of fentanyl required was 0.55 +/- 0.18 mg/hr (mean +/- SD) in Group 1 and 0.53 +/- 0.17 mg/hr in Group 2. Injections of droperidol 7.5 +/- 3.4 mg/hr (Group 1) and midazolam 5.9 +/- 2.3 mg/hr (Group 2) were administered intraoperatively. This redosing regimen was associated with uninterrupted hemodynamic stability, indicating comparable and adequate anesthetic depth. Plasma concentrations of metabolites and hormones indicative of humoral stress activation did not differ between groups. CONCLUSION: Under these clinical conditions, the administration of midazolam, when compared with droperidol, was not associated with signs of any antagonistic or antianalgesic action toward fentanyl-mediated analgesia.

[Effectiveness of preventing hypotension with H1/H2 antagonists before protamine administration]. / Wirksamkeit einer Hypotensionsprophylaxe mit H1/H2-Antagonisten vor Protamingabe.

BACKGROUND: This prospective randomized study was undertaken to evaluate the effects of prophylactic administration of H1/H2 receptor blockers on histamine release and hemodynamic changes after administration of protamine in two groups of patients (n = 20) undergoing elective coronary artery bypass graft surgery. PATIENTS AND METHODS: Group 1 (n = 10) patients were pretreated intravenously with 1 mg/kg ranitidine and 0.1 mg/kg dimetinden 15 min before termination of the extracorporeal circulation; group 2 patients (n = 10) received no medication. After termination of the extracorporeal circulation, heparin was neutralized by administration of 350 U/kg protamine, injected during 4 min via a peripheral vein. Hemodynamic measurements were carried out before the administration of protamine and at 1-min intervals up to 10 min after the injection. Before administration of protamine and 2, 4, 6, 8, and 10 min thereafter, plasma histamine levels were measured using central venous blood samples. RESULTS: In group 1 patients, who were treated prophylactically with H1/H2 receptor blockers, the plasma histamine concentration was 0.21 +/- 0.15 ng/ml (mean +/- SD) and reached a peak value of 0.30 +/- 0.17 ng/ml within 4 min. In group 2 patients, the plasma histamine concentration increased from 0.17 +/- 0.15 to 0.26 +/- 0.24 ng/ml after 10 min. The hemodynamic reactions were comparable in both groups (group 1: decrease in systolic arterial pressure from 118 +/- 16 to 104 +/- 15 mm Hg; group 2: from 111 +/- 19 to 108 +/- 21 mm Hg; differences statistically not significant). The Spearman rank correlation revealed no statistically significant relationship between the slight plasma histamine release and clinically severe decreases of blood pressure that were observed in single patients. CONCLUSION: Histamine release appears unlikely as the mechanism of protamine-induced hypotension. Therefore, general prophylaxis using H1/H2 receptor antagonists does not seem to be justified and cannot be recommended.

[Repeated perioperative administration of fructose and sorbitol in a female patient with hereditary fructose intolerance [HFI)]. / Wiederholte perioperative Applikation von Fructose und Sorbit bei einer Patientin mit hereditärer Fructoseintoleranz (HFI).

The present paper reports on an adult female patient whose hereditary fructose intolerance (HFI) was at first not diagnosed and who, within the space of 2 years after repeated elective surgery and the perioperative administration of fructose and sorbitol, developed "hepatic and renal failure of unclear origin." At a later stage we were able to establish the diagnosis of HFI by means of a fructose tolerance test in both she and her brother, for whom intolerance to fruit and desserts had been known since early childhood. In addition, literature references to fatalities following the parenteral application of fructose and sorbitol were analyzed. During the course of fructose infusion in both the patient and her brother with HFI, the following metabolic changes were noted: hypoglycemia, elevated rise in the blood fructose concentration, hyperlactacidemia, elevated rise in the blood fructose concentration, hyperlactacidemia, and hyperammonemia. These metabolic changes proved to be reversible after discontinuing the fructose infusion. Analysis of the literature on the fatalities following parenteral fructose administration established that fruit and dessert intolerance was known for all collated patients with HFI, and that, clearly, no regular metabolic tests had been conducted.

[Metabolic changes in a patient in the early phase of acute pancreatitis]. / Stoffwechselveränderungen bei einer Patientin in der Frühphase der akuten Pankreatitis.

The present paper reports on the perioperative metabolic changes in a 70-year-old female patient in whom an acute (oedematous) pancreatitis occurred during the transduodenal excision of a villous adenoma of the duodenal papilla. Since blood was taken for metabolic investigations before, during and after surgery, data on the changes in the intermediary metabolism during the early phase of acute pancreatitis in humans was recorded. Raised activity of the pancreatic enzymes amylase and lipase was demonstrable just minutes after extirpation of the papillary tumour after intraoperative cholangiography had been performed via a choledochotomy. This showed occlusion of the duodenal papilla as well as imaging the pancreatic duct. The reflux of bile into the pancreatic duct is considered to be one of the causative factors of acute pancreatitis (Opie-syndrome). The following metabolic changes were registered at surgery and on the first day thereafter: reduction in the serum concentration of cholesterol ester, the triglycerides and the phospholipids by 30 to 50% of the preoperative values respectively, as well as lactacidaemia (up to 60 mg/dl). At the same time, the serum bilirubin concentration and the concentrations of the amino acids alanine and glutamate in the serum were temporarily raised. The question is, whether these metabolic changes were a direct consequence of the activity of the pancreatic enzymes of amino acid and lipid metabolism that were released into the blood, or whether reduced synthesis by the liver (lipoproteins, lecithin: cholesterol-acyl-transferase) was responsible for these changes.

[Metabolic changes in patients with hereditary fructose intolerance. A contribution to the topic of fructose administration for parenteral feeding]. / Stoffwechselveränderungen bei Patienten mit hereditärer Fructoseintoleranz. Ein Beitrag zur Frage der Verwendung von Fructose für die parenterale Ernährung.

The literature contains a number of reports of death following the intravenous administration of fructose in patients with hereditary fructose intolerance (HFI). The aim of the present study was, therefore, to investigate the metabolic changes occurring during intravenous administration of fructose to patients with HFI, with the aim of identifying metabolic parameters that would permit the early diagnosis of HFI. Also, the deaths reported in the literature were analyzed. In three of our own patients with fruit intolerance known since childhood, and in volunteers with normal metabolism, a one-hour intravenous fructose tolerance test (1.7 g fructose/min) was performed. An analysis was done using the usual enzymatic and chemical methods: blood glucose, fructose, lactic acid, serum uric acid, ammonia, free fatty acids, inorganic phosphate, and serum amino acids (ion exchange chromatography). During fructose infusion, the following metabolic changes were detected: hypoglycemia (20 to 60 mg/dl), increase in blood fructose levels (up to 350 mg/dl), hypophosphatemia (2 to 3 mg/dl), hyperlacticacidemia (up to 60 mg/dl), elevation of plasma ammonia levels (up to 120 mg/dl), increased serum glutamate, and a decrease in serum glutamine, as also hyperuricemia (up to 10 mg/dl). On termination of the fructose infusion, these changes were completely reversible. Analysis of the deaths reported in the literature revealed a known intolerance to fruit or sweets, and that no regular metabolic studies were apparently performed. Although HFI is rare, use should be made of the known advantages of sugar substitutes in post-aggression metabolism.(ABSTRACT TRUNCATED AT 250 WORDS)

[Thiamine deficiency as a cause of life threatening lactic acidosis in total parenteral nutrition]. / Thiaminmangel als Ursache lebensbedrohlicher Laktatazidosen bei totaler parenteraler Ernährung.

Two patients aged 37 and 44 years developed life-threatening lactic acidosis following abdominal surgery and a period of about 3 weeks of total parenteral nutrition. Septicaemia and hypoxia were excluded as possible causes. Conventional treatment including high doses of buffer agents was unsuccessful. Thiamine (vitamin B1) depletion was suspected as the cause of the metabolic acidosis, and two doses of 400 mg thiamine were given. In both patients, the lactic acidosis improved immediately, and it disappeared following the second dose of thiamine. Both patients were subsequently discharged as symptom-free. As part of the pyruvate-dehydrogenase (PDH) complex, thiamine was capable of improving the life-threatening situation.