[The effect of age on the spread of spinal anesthesia using isobaric 2% mepivacaine]. / Der Einfluss des Lebensalters auf die Ausbreitung der Spinalanästhesie mit isobarem Mepivacain 2%.

In the elderly, anaesthesia and surgery are associated with higher perioperative mortality and morbidity as compared to younger patients. There is some evidence that spinal anaesthesia may improve the postoperative state of elderly patients. A prospective study was performed to elucidate the effects of age on the characteristics of spinal anaesthesia with isobaric 2% mepivacaine. METHODS. Forty-six patients aged between 17 and 39 years and 48 elderly patients aged between 76 and 87 years having operations on the lower extremities or lower abdomen were investigated. All patients received 4.5 ml plain mepivacaine 2% (90 mg) as a subarachnoid injection in the L3-4 interspace in the sitting position. The patients were turned supine immediately after the injection. Time of onset, extent and duration of analgesia, motor block, and cardiovascular responses were assessed. The segmental level of sensory loss was tested using the pin-prick method. RESULTS. It was found that the time to maximal motor blockade was significantly decreased in the older age group compared to the younger group (7.9 vs 11.5 min). In the older group, the time to maximum spread was significantly shorter (11.4 vs 13.6 min). A significantly higher sensory block was obtained in the older group (T8 vs T10). The mean duration of analgesia or motor blockade did not differ significantly (200.7 vs 192.8 min). There were no unacceptably high degrees of spinal blockade. In the older group there was a tendency to a greater decrease in systolic arterial pressure as compared to preanaesthetic values (23.7% vs 16.3%) and greater falls in diastolic blood pressure were observed in the older group (22.1% vs 14.4%). A greater volume of lactated Ringer's solution was necessary in the older group (14.8 vs 10.3 ml/kg). Postspinal headache was encountered in 3 patients in the younger group and 2 in the older group. DISCUSSION. It is concluded that there was a tendency for greater spread of spinal analgesia with isobaric 2% mepivacaine in the elderly. The clinical significance of this finding is limited. In elderly patients hypotension is more common than in younger patients, but might not be related solely to age or extent of the neural blockade.

[Onset of the effect and intubation conditions following atracurium, verocuronium and suxamethonium]. / Wirkungseintritt und Intubationsbedingungen nach Atracurium, Vecuronium und Suxamethonium.

1. The onset of neuromuscular blockade following i.v. injection of atracurium 0.3, 0.4, or 0.5 mg/kg; vecuronium 0.08 or 0.1 mg/kg; and succinylcholine 1.0 mg/kg was studied in 205 adult patients during induction of anesthesia by means of the compound action potential (EMG) of the hypothenar muscle, which was indirectly stimulated via the ulnar nerve above the wrist, using the Datex Relaxograph. At the same time, the intubation conditions at 0.5, 1, 2, or 3 min after injection were assessed using a scoring system (Crul 1983) related to ease of laryngoscopy, movement of vocal cords and coughing, and reflex movements of the extremities. 2. Neuromuscular blockade and intubation conditions 2 min after administration of atracurium 0.3 mg/kg were 60 +/- 10% and 8.7 +/- 0.3; after 0.4 mg/kg 74 +/- 4% and 10.3 +/- 0.3; and after 0.5 mg/kg 86 +/- 5% and 11.8 +/- 0.2. After 0.08 mg/kg vecuronium 76 +/- 3% and 7.4 +/- 0.5 were recorded and after 0.1 mg/kg 85 +/- 6% and 10.5 +/- 0.4. Motor blockade 1 min after succinylcholine was 98 +/- 2% and intubation conditions scored 11.3 +/- 0.3. Relating intubation conditions to neuromuscular blockade yielded a close correlation and surprisingly good or very good intubation conditions (score more than 10) at a motor blockade of 80% (resp. 20% transmission). 3. Although succinylcholine is still the muscle relaxant with the most rapid onset of action, the new drug atracurium seems to satisfactorily facilitate tracheal intubation within an acceptably short time interval of 2 min after injection.(ABSTRACT TRUNCATED AT 250 WORDS)

[Atracurium: neuromuscular blockade in repeated administration]. / Atracurium: Die neuromuskuläre Blockade bei wiederholter Gabe.

The neuromuscular blocking action of repeated injections of atracurium and vecuronium was studied in 74 surgical patients during balanced anaesthesia (methohexitone or etomidate, intubation after suxamethonium, fentanyl, droperidol, N2O). The initial bolus dose (ID) of atracurium was 0.25 mg/kg and of vecuronium 0.05 mg/kg followed by repeated increments (RD) of atracurium 0.1 mg/kg and vecuronium 0.0125 mg/kg when neuromuscular function (EMG) had recovered to about 30% of pre-relaxant control. Dose-response relationships revealed atracurium to be about 1/5 as potent as vecuronium; the ED50 of atracurium was 0.13 +/- 0.03 mg/kg and of vecuronium 0.023 +/- 0.007 mg/kg. The ID of both relaxants produced a neuromuscular blockade of about 90% within 4 min. The duration from the time of injection to 30% recovery was slightly longer in atracurium 26 +/- 9 min. In all patients the RD produced within 3.5 min satisfactory muscle relaxation with a neuromuscular block of about 85%. The mean duration of atracurium (18 min) was 5-10 min longer than of vecuronium (12 min). To maintain good surgical relaxation (more than 70% blockade) atracurium 0.32 mg/kg X h and vecuronium 0.056 mg/kg X h were required. No cumulation could be measured after repeated injections. The recovery time of atracurium and vecuronium at the end of anaesthesia was 10-12 min. Neither cardiovascular side-effects nor signs of histamine release were observed after both relaxants in our particular dose range. It is concluded, that atracurium is a favourable blocker for anaesthetic practice: The time of onset is approximately the same compared with vecuronium. The duration of action, however, is slightly longer but still truly intermediate long.(ABSTRACT TRUNCATED AT 250 WORDS)

[Vecuronium: onset of effect and intubation conditions in comparison to pancuronium and suxamethonium]. / Vecuronium: Wirkungseintritt und Intubationsbedingungen im Vergleich mit Pancuronium und Suxamethonium.

The onset of neuromuscular blockade following the i.v. injection of vecuronium and pancuronium 0.05, 0.08 or 0.1 mg/kg and suxamethonium 0.5 or 1.0 mg/kg was studied in 304 patients during induction of anaesthesia by means of the compound action potential derived from the adductor pollicis muscle, which was indirectly stimulated via the ulnar nerve. The intubation conditions 1-5 min after injection were assessed using a scoring system related to ease of laryngoscopy, movement of vocal cords and coughing, and reflex movements of extremities. Development of motor blockade was time- and dose-dependent. After administration of 0.1 mg/kg vecuronium, the actual maximum effect (more than 90% block) was established within 4 min; after 0.1 mg/kg pancuronium within 6 min and after 1.0 mg/kg suxamethonium within 2 min. Intubation conditions improved with time. After 0.1 mg/kg vecuronium atraumatic intubation was possible within 2 min and after 0.1 mg/kg pancuronium within 4 min. Following 1.0 mg/kg suxamethonium, optimum intubation conditions were achieved within 1 min. Although suxamethonium acts the fastest and tracheal intubation can be achieved within 0.5-1.0 min, its use involves certain side effects and disadvantages. Vecuronium acts considerably faster than pancuronium and good or excellent intubation conditions are present within 2 min. Suxamethonium is no longer the muscle relaxant of choice for intubation except for crash intubation, e.g., in patients with a full stomach.

Differential increase in potency of neuromuscular blocking agents by enflurane and halothane.

Cumulative dose-response curves of suxamethonium, tubocurarine, and pancuronium were constructed in 142 patients under enflurane and halothane anesthesia, and neuroleptic anesthesia (control group). The dose-response curves shifted to the left with increasing inspired concentrations of enflurane and halothane, thus indicating an increase in neuromuscular blocking potency. An evaluation of the ED50 shows that this increase is quite different for the three relaxants studied. Enflurane has a significantly greater synergistic effect than halothane. Beside other mechanisms and sites of action, which are briefly discussed, the recently proposed transient-state concept of relaxant-receptor interaction is applied to explain the increase in affinity at the receptor level.

The neuromuscular blocking action of suxamethonium following intravenous and intramuscular administration.

In 35 anesthetized adult patients the neuromuscular blocking effect of suxamethonium (0.8-2.4 mg X kg-1) following i.v. or i.m. administration was studied by means of mechanomyograms of the hand muscles after electrical stimulation of the ulnar nerve (0.2 Hz, 100-120 volts, 0.2 ms). Compared with i.v. suxamethonium (= 1.0) the myoneural blocking activity of i.m. suxamethonium was less effective (0.128), the rate of onset slower (0.174), and the duration of action longer (1.4 to 1.7). According to the dose-response relationship, suxamethonium 3.0-4.0 mg X kg-1 should be administered i.m. to achieve complete neuromuscular blockade.

[Anaesthesia in a patient susceptible to malignant hyperthermia (author's transl)]. / Narkoseführung bei Gefährdung durch maligne Hyperthermie.

A 13 year old girl who had suffered from an abortive form of malignant hyperthermia during tonsillectomy eight years before was scheduled for orthopaedic surgery. Dantrolene sodium, 3 mg/kg orally, was given prophylactically the day before surgery; preanaesthetic medication consisted of Thalamonal, a fixed combination of droperidol and fentanyl; anaesthesia was induced with methohexitone and maintained as neurolept anaesthesia with fentanyl and droperidol; tubocurarine was administered for tracheal intubation and intraoperative neuromuscular blockade. Using this anaesthetic regimen no adverse reaction was triggered.

[On the interaction of combinations of nondepolarizing neuromuscular blocking drugs (author's transl)]. / Uber den Synergismus bei der Kombination von nichtdepolarisierenden Muskelrelaxantien.

The interaction (addition or potentiation) of combinations of the ED20 and of the ED50 of pancuronium (0.01 and 0.0165 mg/kg), tubocurarine (0.06 and 0.10 mg/kg), and gallamine (0.25 and 0.41 mg/kg) was studied in 136 patients during general anaesthesia (methohexitone, fentanyl, droperidol, N2O; normoventilation). - 2. Neuromuscular blocking activity was quantified by means of mechanomyograms of the hand muscles following supramaximal electrical stimulation of the ulnar nerve (100-125 V, 0.2 ms, 0.2 Hz). - 3. The combinations of the ED20 and of the ED50 of the three muscle relaxants resulted in an nonlinear manner in 60% and 90% twitch inhibition. - 4. The duration of action of the combinations of the ED20 and of the ED50 did not exceed the duration of blockade by the longest acting individual component given alone. - 5. The nonlinear increase in response following the combination of equieffective doses of muscle relaxants corresponds with the nonlinear shape of dose-response curves and can be described as an additive interaction.

[On the time course of action of nondepolarizing neuromuscular blocking drugs (author's transl)]. / Uber den Wirkungseintritt und die Wirkungsdauer von nichtdepolarisierenden Muskelrelaxantien.

1. Time of onset and duration of action of various doses of pancuronium, tubocurarine, alcuronium , metocurine or dimethyltubocurarine, gallamine and fazadinium were studied by means of mechanomyograms of the hand muscles (twitch) following supramaximal electrical stimulation of the ulnar nerve (100-120 V, 0.2 ms, 0.2 Hz) in 293 patients during neurolept anaesthesia. -2. With an intravenous injection rate of about 5s there was no difference in latency time, however, the time of onset was found to be dose dependent. At equipotent conditions (ED95) the onset time correlated with the molecular weight of the muscle relaxants. -3. As expected the duration of action was dose-dependent. Following equi-effective doses (ED95) the duration of action correlated closely with the molecular weight. -4. The relation between the duration of action and the dosage of a muscle relaxant could sufficiently be described by the equation Y = a x Yb and straightened applying a double-logarithmic plot. The values of a and b for various degrees of recovery were obtained by regression analysis. Thus, the duration of action can be predicted by substituting of dose values into the above equation.

[On dose-response curves and the receptor interaction of nondepolarizing neuromuscular blocking drugs (author's transl)]. / Uber Dosis-Wirkungskurven und die Rezeptor-Wechselwirkung von nichtdepolarisierenden Muskelrelaxantien.

1. Dose-response curves of alcuronium, fazadinium, gallamine, metocurine (dimethltubocurarine), pancuronium, and tubocurarine were obtained from 362 surgical patients during general anaesthesia (barbiturate, fentanyl, droperidol, N2O; normoventilation) by means of mechanomyograms of the hand muscles after supramaximal electrical stimulation (100-125 V, 0.2 ms, 0.2 Hz) of the ulnar nerve. - 2. In a conventional semilogarithmic plot of effect E/Emax versus dose D the sigmoid-shaped curves exhibit a parallel shift with almost the same slopes. - 3. A linear plot of E/Emax against D yields curves intersecting by extrapolation with the ordinate at a point s below zero which indicates a threshold phenomenon in the dose-response relation and gives the value for this threshold (s=60-80). - 4. A double-reciprocal plot of 1/(E/Emax) versus 1/D does not result in straight lines, indicating a lack of linear proportionality between receptor occupancy and effect. The curves are straightened plotting 1/[(E+S)/(Emax+S)] versus 1/D. - 5. From our results which are supported by the "margin of safety" concept of neuromuscular transmission, it is supposed that the relation between neuromuscular blocking drugs and nicotinic receptors does not follow the classical occupation theory based on the law of mass action.

[The effect of muscle relaxants under general anesthesia. A "transient-state concept" of muscle relaxant-receptor interaction]. / Zur Wirkung von Muskelrelaxantien unter Narkosebedingungen. Ein "Transient-state concept" der Muskelrelaxans-Rezeptor-Interaktion.

Different aspects of clinical neuromuscular blockade were studied in 892 patients under general anaesthesia by means of mechanomyograms of the hand muscles after ulnar nerve stimulation. Several phenomena and results could not be explained satisfactorily by the occupation theory of drug-receptor interaction.

Influence off haemodilution on the potency of neuromuscular blocking drugs.

The potencies of suxamethonium, pancuronium, and tubocurarine were increased, as shown by a parallel shift to the left of cumulative dose-response curves, following normovolaemic haemodilution before operation. This is attributed to an increase in cardiac output, to a decrease in protein binding and, in the case of suxamethonium, to a decrease in cholinesterase activity.

[Haemodilution and duration of action of muscle relaxants (author's transl)]. / Hämodilution und Wirkungsdauer von Muskelrelaxantien.

As indicated by time-effect diagrams the duration of action of the ED90 of succinylcholine (0.3 mg/kg), pancuronium (0.033 mg/kg), and tubocurarine (0.21 mg/kg) was prolonged following preoperative normovolemic haemodilution. This influence is assumed to be due to a lower protein binding and cholinesterase activity, to an increase of cardiac output and muscle perfusion and to a higher occupancy of the receptor at the motor endplate by muscle relaxants.

[On the monitoring of neuromuscular blockade during anaesthesia (author's transl)]. / Zur Uberwachung der Muskelrelaxation während der Narkose

Objective evaluation of muscle relaxation during surgery is possible only by indirect stimulation of a skeletal muscle by means of a peripheral nerve stimulator. Most frequently the ulnar nerve is electrically stimulated and the resulting contraction of the hand muscles, i.e., twitching of the fingers is observed. This direct observation of the finger twitches induced by a nerve stimulator provides valuable information a) on the actual magnitude of neuromuscular blockade, b) on the development of a dual block following suxamethonium, c) on the need for more muscle relaxant, d) on the reversal of muscle paralysis by a cholinesterase inhibiting agent, and finally e) on the differential diagnosis of prolonged postoperative apnoea. By employing a nerve stimulator, the neuromuscular blocking agents can be titrated according to the surgical requirements and overdosage can be avoided. The clinical judgement of muscle relaxation by the anaesthesiologist should be accompanied by a more quantitative and objective evaluation, making use of the nerve stimulator.

[On the inhibition of cholinesterases by pancuronium (author's transl)]. / Zur Cholinesterase-Hemmung durch Pancuronium

1. The inhibition by pancuronium of acetylcholinesterase (AChE) and of plasma cholinesterase (ChE) was investigated in vitro regarding a) the sensitivity of both enzymes; b) the mechanism and constants of inhibition; and c) the relationship between the neuromuscular blocking and the anticholinesterase activity of pancuronium. 2. Pancuronium is a reversible inhibitor of both AChE and ChE. The inhibitory potency regarding ChE ([I]50=2.7 X 10(-7) M; Ki=4.2 X 10(-8) M) is highly selective and about 1000-fold higher than compared to AChE ([I]50=2.4 X 10(-4) M; Ki=3.5 X 10(-5) M). 3. The kinetic analysis by means of an Lineweaver-Burk plot and an Arunlakshana-Schild plot displayed a pure competitive mechanism of inhibition. 4. The inhibition of AChE and ChE is thought to be induced by a reversible binding of pancuronium to the anionic subsite of the active center, thus decreasing the formation of the primary enzyme-substrate complex. 5. The clinical administration of pancuronium for muscular relaxation during anaesthesia (0.01-0.08 mg/kg) will result in a concentration of approximately 10(-7)=10(-6) M in the extracellular fluid. Thus, an inhibition of plasma ChE can be expected to occur under clinical conditions, however, probably without practical significance.