Interaction of midazolam with the nicotinic acetylcholine receptor of mouse myotubes.

The effects of midazolam on the peripheral embryonic nicotinergic acetylcholine receptor (nAChR) of mouse myotubes were studied to elucidate the mechanism of its effect on neuromuscular transmission. Standard patch clamp techniques on outside-out patches were used. Pulses of 10(-4) M acetylcholine (ACh) applied by a liquid filament switch technique elicited macroscopic channel currents with a peak current amplitude of approximately 40 pA within <1 ms. The current decayed with a time constant of 30-100 ms due to desensitization. When midazolam was added in stepwise increased concentrations (10(-7) M to 7 x 10(-4) M) to the pulses, the current decay became bi-exponential, and a concentration-dependent decrease of the fast component of decay was observed. The current amplitude, however, was reduced slightly, and only at high concentrations of midazolam. This may indicate that midazolam binds to the open channel to cause the block. The rate constant of block (b(+1)) was found to be 1.8 x 10(6) M/s. Recovery experiments revealed a rate of unblocking (b(-1)) of approximately 2 x 10(-1) s(-1). After preincubation of the patches with midazolam, a substantial reduction of the current amplitude was seen at very low midazolam concentrations (<10(-7) M), which suggests an additional closed channel block with a Kd of approximately 10(-6) M. This closed channel block may be responsible for the muscle-relaxing effects of midazolam.

Ketamine blocks currents through mammalian nicotinic acetylcholine receptor channels by interaction with both the open and the closed state.

Single channel recordings have shown that ketamine (Ket) decreases the open time of the nicotinic acetylcholine receptor channel (nAChR). The present experiments on simultaneous openings of the nAChRs of mouse myotubes investigate the interaction of Ket with the open as well as with the closed state of the channels. The patch-clamp technique was used to record currents activated by 10(-4) M acetylcholine (ACh) in the outside-out mode. ACh together with increasing concentrations of Ket was applied with a piezo-driven system. In a second protocol, the patches were preexposed to Ket before activation with ACh. With addition of Ket, the currents showed a biexponential decay, indicating an open-channel block. The peak current amplitude decreased reversibly and in a concentration-dependent manner. The rate constants of block (b+1) and of unblock (b-1) were modeled by computer simulation and were found to be: b+1 = 3 x 10(6) M/s, b-1 = 100/s. Preexposure of the patches to Ket revealed an additional block with a KD of approximately 2 x 10(-6) M, which is below clinical concentrations. These data suggest that Ket also interacts with the closed state of the nAChR.

[Neuromuscular and cardiovascular effect of mivacurium in anesthesia induction in patients with renal failure]. / Die neuromuskuläre und kardiovaskuläre Wirkung von Mivacurium bei der Narkoseeinleitung von Patienten mit Niereninsuffizienz.

OBJECTIVE: Mivacurium produces a prolonged neuromuscular block (NMB) in anuric patients (13), in spite of its rapid hydrolysis by pseudocholinesterase (PChE) which is independent of renal function (17). In the present study the pharmacodynamics and the cardiovascular effects of a bolus dose of mivacurium (0.15 mg/kg) in relation to impairment of renal function were evaluated. METHODS: 60 patients (ASA class 2-4) were assigned to one of three groups according to the degree of renal dysfunction. Creatinine clearance (Krea-Cl) as a measure of renal function was calculated using weight, age, sex and serum creatinine concentrations. Group C (control): Krea-Cl > 50 ml/min; group P (preterminal): 20 ml/min < Krea-Cl < 50 ml/min; group T (terminal): Krea-Cl < 20 ml/min. PChE activity and dibucaine numbers were assessed preoperatively. Neuromuscular transmission (Train-of-Four) was monitored using electromyography (Relaxograph, Datex Inc.) with stimulation of the ulnar nerve. The response was recorded from the hypothenar muscle. Five minutes after induction of anaesthesia with propofol and fentanyl, 0.15 mg/kg mivacurium was given i.v. over 30 s. 150 s later patients were intubated. Anaesthesia was maintained by propofol (2-10 mg/kg/h) and fentanyl (0-5 micrograms/kg/h) infusion. Patients were ventilated with oxygen/nitrous oxide (FiO2 = 0.35). As soon as T1 recovered to 5% or more, mivacurium was administered continuously and this part of the study was finished. Times of onset (onset 10; onsetmax), maximal neuromuscular block (NMBmax), neuromuscular block when intubation was started (NMBTubus), and duration 5% (dur 5) were calculated. Arterial blood pressure and heart rate were recorded before anaesthesia, after induction of anaesthesia, 2-times after mivacurium application, and after intubation. All data were compared using Kruskal-Wallis test corrected for multiple comparisons, Friedman test, or chi 2-test (*: p < 0.05). Logarithms of dur 5 and PChEd were correlated using linear regression. RESULTS: Demographic data were comparable between all groups. PChEd was 3.7 (3.0/4.1) kU/l in group C, 3.2 (2.2/4.8) kU/l in group P, and 3.5 (2.5/4.0) kU/l in group T, respectively. There were no differences between groups, neither in the NMBmax, in NMBTubus, or in onset times. But dur 5 was significantly longer in patients with renal impairment, both preterminal and also end-stage (medians: 11 min in group K, 16 min in group P, 17 min in group T). Emphasis, however, is put on the broad range between 5 and 47 min of dur 5 in group P, and between 6 and 53 min in patients of group T which is clinically more important than the differences in the median values. Dur 5 correlates with PChEd (p = 0.0001). Intubation conditions were excellent (relaxed vocal cords, easy passage of the tube, without coughing) in approximately 70% of all 59 patients without significant differences between groups. In 8 patients conditions were poor (successful intubation, inspite of moderately adducted vocal cords, but moderate coughing after passage of the endotracheal tube). There were no clinically relevant hemodynamic changes in each group in the time between injection of 0.15 mg/kg mivacurium slowly and intubation 2.5 min later. DISCUSSION: Our findings suggest that 0.15 mg/kg mivacurium is an effective and safe intubation dose in healthy patients as well as in patients with renal impairment, inspite of a prolonged duration in patients with renal impairment. Low PChE in some, but not in all patients with a renal dysfunction indicates involvement of impaired hepatic function. There was a close correlation between the PChEd and dur 5. Therefore mivacurium dosage should be reduced in patients with compromised renal function, mainly if there are additional systemic, especially hepatic diseases. Thus, in patients with impaired renal function, relaxometry may be of high valu

[Enflurane blocks ion current through the nicotinic acetylcholine receptor]. / Enfluran blockiert den Ionenstrom durch den nikotinischen Acetylcholinrezeptor.

AIM: The study investigates the influence of enflurane (EN) on macroscopic currents of the nicotinic acetylcholinergic receptor channel (nAChR). This ion channel is a representative member of the superfamily of ligand-gated receptor channels and is better characterized than all the other receptors in respect of structure and function. METHODS: For the experiments the patch-clamp technique was used to study the embryonic type of the nAChR expressed by cultured mouse-myotubes. Patch-clamp recordings were performed in the outside-out-mode from these preparations. To match the rapid desensitization kinetics of ligand-activated ion channels, a liquid filament switch technique was used for the application of agonists to the excised patches. This technique allows for change of solution within 300 microseconds. We used a saturating concentration of 10(-4) M acetylcholine (ACh), activating almost all available ion channels on a patch. Pulses of 10(-4) M ACh together with EN in different concentrations were applied repetitively. RESULTS: The current elicited by 10(-4) M ACh is reduced reversibly in a concentration-dependent manner by EN in clinically relevant concentrations: 1,44 x 10(-5) M EN inhibit about 10%, 1.44 x 10(-4) M 25%, 1.44 x 10(-3) M 35%, and 1.44 x 10(-2) M 75% of the ion flux (averaged results from 48 patches). EN decreases the time constant of the current decay. This acceleration of desensitisation kinetics is partly reversible if followed by application of 10(-4) M ACh. CONCLUSION: In this study we were able to show that EN reduces the currents of the ligand-gated embryonic-like nAChR in clinically relevant concentrations. Volatile anaesthetics are known to influence GABAA-, glutamate-, and glycine- activated receptors, which are members of the same family of ligand-gated receptor-channel units. Thus, the action of volatile anaesthetics on ligand-gated receptors may play a role in the mechanism of general anaesthesia. The interaction of volatile anaesthetics with nondepolarising neuromuscular blockers may also be based on this effect at the neuromuscular junction.

Effect of renal function on neuromuscular block induced by continuous infusion of mivacurium.

We have studied the effect of renal function on the pharmacodynamics of mivacurium. Sixty patients were allocated to three groups according to creatinine clearance: group C (control), creatinine clearance > 50 ml min-1; group P (preterminal renal failure), creatinine clearance < 50 ml min-1 > 20 ml min-1; group T(terminal renal failure), creatinine clearance < 20 ml min-1. Neuromuscular transmission (train-of-four) was monitored using electromyography from the hypothenar muscle with stimulation of the ulnar nerve. After an initial bolus, mivacurium was administered continuously to maintain a T1 of 5 (4)% of baseline. The dose of mivacurium necessary to maintain 95% neuromuscular block was similar in patients with normal renal function and patients with different levels of renal impairment. Recovery from neuromuscular block after ceasing mivacurium infusion was significantly prolonged in patients with preterminal renal impairment. There was a close correlation between mivacurium pharmacodynamics and pseudocholinesterase activity, but not creatinine clearance.

[Effect of capnoperitoneum on postoperative carbon dioxide homeostasis]. / Auswirkungen des Kapnoperitoneums auf den postoperativen Kohlendioxidhaushalt.

After laparoscopic cholecystectomy, carbon dioxide (CO2) must be exhaled after resorption from the abdominal cavity. There is controversy about the amount and relevance of postoperative CO2 resorption. Without continuous postoperative monitoring, after laparoscopic cholecystectomy a certain risk may consist in unnoticed hypercapnia due to CO2 resorption. Studies exist on the course of end-expiratory CO2 (Pe-CO2) alone over a longer postoperative period of time in extubated patients during spontaneous breathing. The goal of this prospective study was to investigate the amount of CO2 resorbed from the abdominal cavity in the postoperative period by means of CO2 metabolism. METHODS. After giving informed consent to the study, which was approved by the local ethics committee, 20 patients underwent laparoscopic cholecystectomy. All patients received general endotracheal anaesthesia. After induction, total IV anaesthesia was maintained using fentanyl, propofol, and atracurium. Patients were ventilated with oxygen in air (FiO2 0.4). The intra-abdominal pressure during the surgical procedure ranged from 12 to 14 mm Hg. Thirty minutes after releasing the capnoperitoneum (KP), CO2 elimination (VCO2), oxygen uptake (VO2), and respiratory quotient (RQ) were measured every minute for 1 h by indirect calorimetry using the metabolic monitor Deltatrac according to the principle of Canopy. Assuming an unchanged metabolism, the CO2 resorption (delta VCO2) at any given time (t) can be calculated from delta VCO2 (t) = VCO2 (t)-RQ(preop) VO2 (t). It was thus necessary to define the patient's metabolism on the day of operation. The first data were collected before surgery and after introduction of the arterial and venous cannulae for a 15-min period. Measuring point 0 was determined after exsufflation of the KP and emptying of the remaining CO2 via manual compression by the surgeon at the end of surgery. Patient's tracheas were extubated and metabolic monitoring started 30 min after release of the KP for 60 min. Simultaneously, a nasal side-stream capnometry probe was placed and the PeCO2 and respiratory frequency (RF) were obtained by the Capnomac Ultima (Datex) and registered every minute as well. Values were averaged over four periods of 15 min each. An arterial blood gas sample was drawn at the end of every 15-min period. Postoperative pain was scored by a visual analog scale and completed by a subjective index questionnaire on general well-being. All data were analysed by the Friedman or Wilcoxon test; P < 0.05 was considered significant. RESULTS. The findings do not indicate CO2 resorption in the postoperative period after laparoscopic cholecystectomy (Tables 2 and 3, Fig. 1). Arterial CO2 as well as PeCO2 were elevated postoperatively (45 mm Hg vs. 36 mm Hg intraoperatively), while VCO2 and VO2 were unchanged when compared to the preoperative measuring period. The postoperative RF was comparable to preoperative values. Calculated delta CO2 was lower than 10 ml/min and within accuracy of measurements. The post-operative pain index ranged between 3 and 4, and 3.75-15 mg piritramid was administered. All patients felt tired immediately after the operation, but scores improved slightly at the end of the 60-min period of metabolic monitoring. CONCLUSIONS. There is no significant resorption of CO2 from the abdominal cavity later than 30 min after releasing the KP. Up to this time, any CO2 remaining in the abdominal cavity after careful emptying by the surgeon has been resorbed and exhaled. An increased PeCO2 as late as 30 to 90 min postoperatively should rather be considered a consequence of residual anaesthetics and narcotics than of CO2 resorption.

[Dose-response relationship of atracurium in underweight, normal and overweight patients]. / Zur Dosis-Wirkungsbeziehung von Atracurium bei unter-, normal- und übergewichtigen Patienten.

OBJECTIVE: In patients with extreme stature or build, estimation of individual dosage requirements of muscle relaxants by body weight is unreliable. To define a more precise guideline for dosage of atracurium in clinical practice we compared in this prospective study in patients with a wide range of body weights the cumulative effective dose for a 95% twitch depression (ED95), the dosage necessary to maintain a 95% twitch depression (DD95) and the recovery from a 95% neuromuscular block with simple demographic data such as body weight, body size, body surface area and lean body mass (LBM). METHODS: 30 patients were divided into three groups according to the individual body weight: underweight, normal, overweight. The electromyographic response was monitored using train-of-four stimuli applied to the ulnar nerve. Neuromuscular block was induced by constant infusion of atracurium; the dose required for a 95% twitch depression was registered as ED95. The infusion rate was then adjusted to maintain a constant electromyographic response of the first twitch of 5 +/- 1% for at least 30 minutes and the required dose of atracurium was recorded as DD95. The neuromuscular recovery was studied regarding T1 and T4-ratio. Data are given as medians (25%-/75%-quartiles). RESULTS AND DISCUSSION: The cumulative ED95 in underweight patients (0.34 (0.31/0.48) mg/kg) exceeded (P < 0.05) those in normal (0.29 (0.26/0.30) mg/kg) and in overweight patients (0.22 (0.18/0.26) mg/kg). In contrast to calculations according to the normal weight (Mn) no difference in ED95 was seen between groups (normal: 0.29 (0.26/0.30) mg/kg Mn; underweight: 0.28 (0.26/0.32) mg/kg Mn; overweight: 0.31 (0.25/0.32) mg/kg Mn). The individual DD95 was best correlated with LBM (r = 0.465, p < 0.01). In view of the difficulty of estimating LBM in routine clinical practice it is emphasized that DD95 correlates only slightly less with normal weight (r = 0.404, p < 0.05). In spite of the variability of DD95 with regard to body weight, the recovery of neuromuscular transmission in the patients of the three groups is comparable. As a constant neuromuscular block cannot be maintained without monitoring muscular evoked responses, even if body build is taken into account, neuromuscular monitoring is advocated for longer infusion of atracurium.

[Comparative study of the recovery phase. Laparoscopic cholecystectomy following isoflurane, methohexital and propofol anesthesia]. / Vergleichende Untersuchungen der Aufwachphase. Laparoskopische Cholezystektomie nach Isofluran-, Methohexital- und Propofolanästhesie.

Total intravenous anaesthesia (TIVA) is increasingly used in short-stay surgery such as laparoscopic cholecystectomy. TIVA may provide fast recovery of psychomotor function, thus being of benefit to both the patient's behaviour and postoperative management. The purpose of this prospective study was to compare postoperative recovery from TIVA using propofol or methohexitone as the hypnotic component and balanced anaesthesia with isoflurane. PATIENTS AND METHODS. After giving informed consent and approval by the ethical committee of our hospital, 51 patients (ASA I, II) were investigated in a prospective study. Patients were randomised to receive either isoflurane, methohexitone, or propofol. Perioperative management with regard to premedication, intraoperative analgesia, relaxation, ventilation, and postoperative analgesia was carried out identically for all groups. Postoperative vigilance, pain, and nausea scores were assessed 15, 30, 60, 120, and 360 min after extubation with a visual analogue scale (VAS). At the same points, psychomotor recovery was investigated with the following assays: sedation as shown in Table 1; orientation with ten questions as to person, time, and location; memory as expressed by the patient's ability to repeat five words; a calculation test with five subtractions of the number 7 beginning from 100; and word generation by the number of words with an initial "m" given within 1 min and with animal names. Data were analysed with Kruskal Wallis' test for multiple comparisons between the groups and with Friedman's test for repeated measurements. All values are given as medians (interquartile range) or ranges. RESULTS. There was no difference between the groups' physical condition (Table 2). All intraoperative parameters compared well between groups; the management of anaesthesia was smoother with isoflurane than with the other anaesthetics. Psychomotor recovery was somewhat faster in the propofol group than the methohexitone group, as indicated by sedation score, orientation, memory and calculation tests (Table 4), word generation tests (Fig. 4), and subjective vigilance score (Fig. 3). The difference in recovery time between the propofol and isoflurane groups was minimal and without any significance or relevance. The incidence of postoperative nausea was significantly lower after balanced anaesthesia with isoflurane (24%, P < 0.05) as compared to TIVA with either propofol (53%) or methohexitone (41%). However, there were only minor differences between the groups; the ability to cooperate and be mobilised was not limited. DISCUSSION. Each of the three techniques used in this study is suitable for anaesthesia in patients undergoing laparoscopic cholecystectomy. Since fast recovery of vigilance and psychomotor function is very important in outpatient surgery, opioid-supplemented propofol anaesthesia is well established. Inhalation anaesthesia with isoflurane in air/oxygen without adding nitrous oxide compares well to propofol TIVA for laparoscopic surgery.

[Electroencephalographic demonstration of central nervous system effects of different premedication regimens]. / Elektroenzephalographische Darstellung der zentralen Auswirkungen verschiedener Prämedikationsregimes.

INTRODUCTION: For many years, the main goal of premedication was prevention of the dangerous side effects sometimes encountered in anesthetics with anticholinergics, antiemetic antihistaminics, and opioids. Because the rules were always preoperative fasting, premedication was administered i.m. Thus, the onset of action was within 15-30 min from administration. In recent years, with the introduction of newer anesthetics with fewer side effects, anxiolysis became the main aim in premedication. Moreover, the oral route became popular since it obviously did not increase the acidity or volume of the gastric content. However, the uptake and thus onset of action of orally administered drugs may take longer and can differ considerably between individual patients. Therefore, the optimum interval between administration and induction of anesthesia remains controversial. The present study was carried out to examine the time course of drug action and the effects of different premedication regimens on the electroencephalogram (EEG). PATIENTS AND METHODS: After obtaining informed consent, in 38 unselected adult patients (ASA I and II, < 65 years) scheduled for elective surgery, the EEG was recorded continuously before and after premedication. The patients were randomly assigned to four groups: M: midazolam, 0.2 mg/kg BW orally; N: nordazepam, 0.2 mg/kg BW orally; AP: atropine, 0.5 mg, plus promethazine, 50 mg i.m.; APP: atropine, 0.5 mg, plus promethazine, 50 mg, plus pethidine, 0.7 mg/kg BW i.m. The EEG was recorded for a reference period of 10 min before and a study period of 30 min after premedication. Automated EEG processing was performed with CATEEM (computer-aided topographical electroencephalometry). Surface electrodes were placed according to the 10-20 system. Date were collected via an amplifier (resistance 10 M omega) and a digitalization unit (filter 0.2-35 Hz, sampling rate 512 Hz, 12 bit A/D convertor). The original EEG signals were used in an interpolation algorythm to produce an additional 82 virtual recording points, allowing for high topographical resolution. After spectral analysis (fast Fourier transformation), the different frequency ranges of the EEG power spectrum are displayed in different colors. The screen displays the on-line map with color-based topographical power distribution. In order to achieve a pharmacodynamic time profile, the study period was subdivided into three periods of 10 min each. For clinical evaluation of vigilance, a 6-grade scoring system was used 1 = awake, 6 = not arousable). RESULTS: All data are presented with respect to reference period. The power density of each frequency range for each electrode is integrated over the selected period and mean values are shown. Changes in power density with time are expressed as percentage change from reference period. Biometrical data showed no significant differences between groups. The median vigilance score 30 min after premedication (end of study period) was 4 in groups M, AP, and APP, and 3 in group N. In both benzodiazepine groups, a distinct increase in power density was found in the beta-bands, while in groups AP and APP the increase was most pronounced in the delta and theta bands. In group M, there was a linear increase in beta 1 power up to 310%, while in the beta 2 range there was a 170% maximum within the second period of 10 min. In group N, there was a similar course with a lower increase in beta 1 (220%) and beta 2 (130%). Increases in both beta-bands were most pronounced with frontal electrodes. While group M showed an increase in delta power (150%), together with moderate suppression in alpha (alpha 1 50%, alpha 2 40%), nordazepam caused only a slight increase in delta (124%) and a distinct increase in alpha 2 to 150%, predominantly in the frontal areas. Group APP showed a linear increase in both delta up to 210% and theta power to 190%. (ABSTRACT TRUNCATED)

Block of nicotinic acetylcholine-activated channels of cultured mouse myotubes by isoflurane.

It is well known that volatile anesthetics cause muscle relaxation. A block of nicotinic acetylcholine-activated receptors (nAChRs) in staedy state by isoflurane was recently reported. Pulses of acetylcholine (ACh) were applied to outside-out patches from mouse myotubes using a system for ultra-fast solution exchange allowing the study of the block of nAChRs by isoflurane under conditions similar to the situation during synaptic transmission. Isoflurane in concentrations used during general anesthesia blocked approximately 50% of the receptors within 0.5 ms after application. The block of nAChRs could be partially relieved by application of high concentrations of ACh. Therefore, muscle relaxation and the reduction of the amplitude of postsynaptic currents by isoflurane may be caused by the block of nAChRs reported here.

[Left heart failure in anesthesia in a child pretreated with propranolol--case report]. / Linksherzversagen in Narkose bei einem mit Propranolol vorbehandelten Kind--kasuistischer Beitrag.

A 13-year-old girl suffering from nephrogenic hypertension, treated with high-dose propranolol and other antihypertensive medication, developed acute hypoxaemia (oxygen saturation at 60% at 100% oxygen ventilation) shortly after induction of anaesthesia. The auscultatory findings first suggested bronchospasm; however, specific measures failed to improve pulmonary function. The planned procedure was delayed and further investigations showed acute left heart failure due to beta-blockade combining with general anaesthesia.

[Anesthesia relevant features of laparoscopy--the value of capnometry]. / Anästhesierelevante Besonderheiten der Laparoskopie--Wertigkeit der Kapnometrie.

End-expiratory capnometrical and capnographical data correspond well with blood carbon dioxide content. Carbon dioxide insufflation for laparoscopy results in a big increase in CO2 uptake as well as in respiratory deterioration due to positioning and increased intra-abdominal pressure. We observed 226 female patients during laparoscopy under general anaesthesia (midazolam-alfentanil-atracurium or vecuronium) and artificial ventilation. Airway peak and plateau pressure increased by about 75% as compared to pre-insufflation levels. End-tidal carbon dioxide exceeded pre-insufflation levels by 2 to 19 mmHg (mean 9 mmHg). Both findings were correlated to speed and overall volume of CO2 insufflation. Major cardiocirculatory side-effects were not observed, except for rare bradycardia, which responded to atropine. Considerable regurgitation via or beneath the gastric tube occurred in 52%. Thus, general anaesthesia with endotracheal intubation and consistent monitoring, including capnometry, may be regarded as particularly safe as far as aspiration of gastric contents and ventilatory requirements are concerned.

[The early diagnosis of malignant hyperthermia--the place of end-expiratory CO2 monitoring]. / Frühdiagnose der malignen Hyperthermie--zum Stellenwert des endexspiratorischen CO2-Monitorings.

The authors report on the course of a fulminant malignant hyperthermia (MH) associated with laminectomy in a 29-year-old man who had been healthy up to that time. Succinylcholine and isoflurane were considered to be the causative triggering agents. Progression could be prevented due to an early suspicion raised by end-expiratory CO2 measurement: treatment was instituted immediately (Dantrolene 2mg/kg body weight, oxygen hyperventilation, external cooling, etc.) Serum creatine kinase increased up to almost 50,000 U/l associated with massive myoglobinuria. Residue-free restitution was achieved within a few days. Decisive for an early detection of MH is the routine performance of end-expiratory CO2 measurement which is definitely superior to temperature control and significantly reduces the time that elapses before treatment is initiated.

[Massive and multi-transfusions in polytraumatized patients: long-term serologic markers of hepatitis B, hepatitis C and AIDS]. / Massiv- und Multitransfusion bei polytraumatisierten Patienten: Langfristige serologische Befunde zu Hepatitis B, Hepatitis C und AIDS.

302 out of 712 (42%) consecutive polytraumatized ICU patients received ten or more units of stored blood during primary and/or intensive care (1982 to 1987) treatment. 120 of the 197 surviving patients with an average number of transfusions of 23 (10 to 89) units were followed up after a mean interval of 70 (20 to 104) months. Mean duration of continuous post-ICU hospital stay was 17 (2 to 160) weeks, mean number of additional operative procedures was three (0 to 23). Manifest hepatitis had not occurred, all samples were negative for HIV testing. In nine samples (7.5%), anti-HBc-antibodies were positive, while HBs-antigen was negative. Ten patients (8.3%) tested positive for anti-HCV-antibodies (one combined with positive anti-HBc). The rate of serologically positive samples increased with the number of blood units given, duration of overall hospital stay and/or number of secondary surgery; all these findings failed to prove statistically significant. The rate of seropositivity for anti-HBc-antibodies corresponded well with the rate found in voluntary donors in FRG. Manifest or chronic hepatitis B was not observed. As to hepatitis C, the incidence of seropositivity for anti-HCV was found tenfold higher than in healthy blood donors in FRG. The relevance of this result remains unclear, but might indicate chronic post-transfusional hepatitis with high risk of cirrhosis. Among the patients testing positive for anti-HCV, too, acute manifest hepatitis had not occurred. Recently developed RIBA kits might improve specificity and sensitivity of anti-HCV testing. Thus, the frequency of PTH-C could decrease considerably.

[Lung edema following intestinal irrigation with golytely solution]. / Lungenödem nach Darmspülung mit Golytely-Lösung.

A case of pulmonary edema following whole gut lavage with Golytely's solution is reported. The patient did not suffer from gastrointestinal obstruction, renal dysfunction or cardiac congestion.

Central anticholinergic syndrome (CAS) in anesthesia and intensive care.

Many of the drugs used in anesthesia and intensive care may cause blockade of the central cholinergic neurotransmission. Acetylcholine is of significance in modulation of the interaction among most other central transmitters. The clinical picture of the central cholinergic blockade, known as the central anticholinergic syndrome (CAS), is identical with the central symptoms of atropine intoxication. This behaviour consists of agitation including seizures, restlessness, hallucinations, disorientation or signs of depression such as stupor, coma and respiratory depression. Such disturbances may be induced by opiates, benzodiazepines, phenothiazines, butyrophenones, ketamine, etomidate, propofol, nitrous oxide, and halogenated inhalation anesthetics as well as by H2-blocking agents such as cimetidine. There is an individual predisposition for CAS--but unpredictable from laboratory findings or other signs. Reports of postanesthetic occurrence of the CAS requiring treatment are not unanimous, varying between 1 and 40%. Differential diagnosis of the CAS includes disorders of glucose and electrolyte metabolism, severe hormonal imbalance, respiratory disorders (hypoxia, hypercarbia), hypothermia, hyperthermia and neuropsychiatric diseases (cerebral hypoxia, stroke, catatony, acute psychosis). The CAS may considerably impair the postanesthetic period especially when agitation is prevalent, which may endanger the patient or the surgical results. The diagnosis is confirmed ex iuvantibus by the sudden increase in the acetylcholine level in the brain. This is achieved with physostigmine, a cholinesterase inhibitor able to easily cross the blood-brain barrier. Its peripheral muscarinic effects are minimal. Postanesthetic CAS can be prevented by administration of physostigmine during the anesthesia procedure. During intensive care (IC), agitated forms of CAS may occur in patients undergoing mechanical ventilation, particularly during prolonged high-dose sedation. Artificial ventilation of such patients becomes very difficult and muscle relaxation may be necessary. In these cases of IC-CAS, physostigmine is of value and has proven beneficial during weaning from mechanical ventilation. Dealing with the CAS for more than a decade has improved knowledge of the central cholinergic transmission. For example, it can be said that CAS occurs alongside general anesthesia, being no more than a frequent side-effect. Furthermore, acetylcholine is involved in nociception through the endorphinergic and the serotoninergic systems. There is a close relation between the central cholinergic transmission and actions of nitrous oxide. Moreover, cholinergic transmission is involved in withdrawal from (among others) alcohol, opiates, hallucinogens and nitrous oxide. In some intoxications with psychoactive agents, physostigmine is useful for reversal of the central nervous symptoms of the acute intoxication itself. In addition it can be used for prevention of some withdrawal states. In

[Physostigmine--recent pharmacologic data and their significance for practical use]. / Physostigmin--Neuere pharmakologische Befunde und ihre Bedeutung für den Einsatz in der Praxis.

Physostigmine is widely used for treatment of the central anticholinergic syndrome during recovery from anaesthesia. The drug is also very useful in treatment of intoxicated patients, in differential-diagnostic procedures of coma of unknown origin, and in restoration of vigilance after prolonged sedation for mechanical ventilation. Besides the specific central cholinergic action of physostigmine, several new pharmacological actions have now been established. Analgesic action is dependent on the interaction with the 5-HT (serotoninergic) system and is independent of narcotic or cholinergic agonists. The antianalgetic stress hormone, ACTH, also does not interfere with this action. Physostigmine does not interfere with the anaesthetic state when given during general anaesthesia. It attenuates several withdrawal states, especially alcohol delirium, opiate and nitrous oxide withdrawal syndromes. The drug may offer a protective mechanism against hypoxic damage of the brain and may also be beneficial in amnestic syndromes and sleep disorders. Physostigmine produces central and peripheral cardiovascular stimulation. It has been shown that physostigmine can be useful in prevention and treatment of postanaesthetic behavioural disturbances following anaesthesia with propofol. Number of indications for use of physostigmine has increased considerably.

[The history of scopolamine--with special reference to its use in anesthesia]. / Zur Geschichte des Scopolamin--Unter besonderer Berücksichtigung seiner Anwendung in der Anästhesie.

Potions from plants, now known to contain scopolamine, were used in antiquity and the middle ages. However, wide-spread application of drugs for induction of insensibility to pain did not occur, probably because of side-effects and unpredictable dose-effect relationships. The word "scopolamine" is derived from "Scopolia carniolica", a solanaceous plant so named by Carl von Linné in honour of supposed discoverer, J. A. Scopoli. However, description of the effects and picture of the same plant have been found in A. P. Matthioli's work. Scopolamine is still widely used in anaesthetic practice and has enjoyed applicability in other medical fields. Unethical misuse of scopolamine has been known for a considerable time. Nowadays, the unwanted effects of scopolamine can specifically be antagonized by physostigmine. Scopolamine has been used in folk-lore rituals and enjoys great interest among ethno-pharmacologists.

[Air transportation of patients: a danger of hypoxic organ lesions?]. / Lufttransport von Patienten: Gefahr hypoxischer Organschäden?

As illustrated by two cases, a fall in alveolar oxygen pressure at high altitude, such as during transportation by plane, can cause hypoxic pulmonary failure, especially in patients with already impaired pulmonary or circulatory functions. Arterial oxygen saturation was recorded by pulse oximetry in 14 healthy volunteers and eight patients during air transportation. Oxygen saturation decreased with reduced cabin pressure. Decreased saturation for each 100 mm Hg reduction in cabin pressure was markedly greater in the patients than the healthy volunteers. Pulmonary and circulatory status should be assessed before air transport of patients and if necessary departure delayed. Oxygen ought to be added to inspired air with appropriate supervision in all acutely ill patients. Indications for endotracheal intubation before flight should be generously defined. Continuous pulse oximetry is noninvasive and highly informative. It is urgently recommended that air ambulances be equipped with them.