Incidence of post-anaesthetic arrhythmias in dogs.

OBJECTIVES: To assess the use of Holter monitoring for evaluating the incidence of post-anaesthetic cardiac arrhythmias and associated anaesthetic risk for two different anaesthetic protocols. METHODS: Patients undergoing orthopaedic surgery were randomly divided into two groups with different anaesthetic regimens (group A, isoflurane n = 30; group B, propofol n = 30). Two 24-hour Holter recordings were performed for each patient: the first directly following anaesthesia and the second, as a comparison, on the fifth postoperative day. RESULTS: Although all dogs were healthy on pre-anaesthetic cardiac evaluation, 56 dogs showed arrhythmias in the two 24-hour (Holter) electrocardiograms performed. However, the number of arrhythmias recorded was low in most cases (less than 10 supraventricular extrasystoles and less than 100 ventricular extrasystoles). One patient in group A showed 94 supraventricular extrasystoles during the second monitoring period. Three patients in each group developed more than 100 ventricular extrasystoles during both Holter recordings. There were no statistically significant differences between the two anaesthetic regimens or between the two recordings in both groups. CLINICAL SIGNIFICANCE: The two anaesthetic protocols investigated in this study did not induce an increased incidence of severe arrhythmias in healthy dogs in the post-anaesthetic phase.

[Comparison of the influence of different anesthetic protocols in the development of post-anesthetic arrhythmia in the dog]. / Vergleich des Einflusses verschiedener Narkoseregime in Hinblick auf die postnarkotische Arrhythmieentwicklung beim Hund.

Post-anesthetic holter monitoring was performed in 2 patient groups in order to compare the incidence of cardiac arrhythmias as a result of different anesthetic protocols. The 2 groups differed in their anesthetic protocol. Both groups received levomethadone as pre-anesthetic. The dogs in group A (n = 30) additionally received diazepam, the dogs in group B (n = 30) received propofol instead. Anesthesia was maintained by isoflurane in group A and a propofol constant rate infusion in group B. In each patient 2 holter monitorings were performed. The first recording began directly after anesthesia. As a comparison a second recording was performed on the 5th post-operative day. The recorded number of arrhythmias was low and no statistical difference was demonstrated between the 2 patient groups.

[Long-term EKG in dogs: comparison between a computerized system and visual arrhythmia analysis]. / Das Langzeit-EKG beim Hund: Vergleich zwischen computergesteuerter und visuell ausgewerteter Arrhythmieanalyse.

Based on results of holter ecg recordings taken from 38 dogs the computerized analyses system turned out as method not exactly valuing the frequency and sensitivity of arrhythmias. Despite there was a significant correlation between the computerized and visual arrhythmia analysis for ventricular respectively supraventricular premature beats, in individual cases there was an important aberration between the particular values.

[The effectiveness and tolerance of ramipril in comparison to captopril for heart failure in dogs]. / Untersuchung zur Wirksamkeit und Verträglichkeit von Ramipril im Vergleich zu Captopril bei der Herzinsuffizienz des Hundes.

In this study 43 animals suffering from a decompensated heart failure were treated with one of two different ACE-inhibitors. 16 animals received Captopril, 27 were treated with Ramipril. A clinical examination was performed prior to the onset of therapy. Controls were performed two weeks, six weeks and seven months after the beginning of treatment. In the captopril-group 12 animals improved by at least one degree, four dogs died within the examination period. In the ramipril-group 16 of 27 dogs treated with a dosage of 0.125 mg/kg bw once a day showed an improvement of one or more degree and 6 animals died. In 8 animals the dose of 0.125 mg/kg bw once a day was increased to 0.125 mg/kg bw twice a day which consequently led to an improvement in 4 dogs. Ramipril and captopril were considered equal in tolerance. The study will be continued with a ramipril dosage of 0.25 mg/kg bw once a day in all further patients.

[Longterm ECG in the dog]. / Langzeit-EKG beim Hund.

Holter monitoring was obtained from 44 clinically normal dogs and 68 dogs with heart disease or being suspicious for a cardiopathy. Several employments of the holter monitoring are shown by means of some examples. This method proved to be effective in the diagnosis of syncopes and the review of the therapy of arrhythmias. Limits and difficulties are discussed.

[Treatment of heart failure in dogs with ACe inhibitors: comparison of quinapril and captopril]. / Die Behandlung der Herzinsuffizienz des Hundes mit ACE-Hemmern: Quinapril und Captopril im Vergleich.

In this study 72 dogs the efficacy and safety of quinapril and captopril in the treatment of canine heart failure were found to be comparable. Differences exist between the dosage schedules of both ACE inhibitors. The recommended dosage schedule for the short acting captopril is three times daily 0.5 mg/kg bodyweight. Quinapril belongs to a newer generation of ACE inhibitors with a longer half life. Therefore a dosage of 0.5 mg/kg KGW once daily was in most cases sufficient for a successful therapy. This means that quinapril can ease the management of canine heart failure, because at least in dogs with mild to moderate heart failure the dosing interval is longer compared to captopril. Moreover, the treatment of small dogs is easier, because quinapril is available as 5 mg tablets whereas the smallest captopril tablets contain 12.5 mg agent.

Manifestation of acute intermittent porphyria in patients with chronic inflammatory bowel disease.

In a retrospective study covering 411 acute intermittent porphyria patients, four cases of a coincidence with Crohn's disease or ulcerative colitis were found. Their courses of disease confirmed that patients with chronic inflammatory bowel disease have a higher risk for acute porphyria manifestation. Both malnutrition (glycopenic induction) and sulphasalazine (drug-induced exacerbation) are known as triggering factors for acute porphyric states. Furthermore, diagnosis of acute intermittent porphyria tends to be much more difficult in such cases, as the acute phases of abdominal pain are likely to be associated with the enteral disease process. A delay of diagnosis and therapy of acute hepatic porphyria, however, may endanger the patient by pareses, which could be irreversible or even lethal. Therefore, whenever there is suspicion of a coinciding acute porphyria, urinary screening tests for porphyria should immediately be performed and, if a coinciding acute hepatic porphyria is diagnosed, porphyrogenic drugs like sulphasalazine should be avoided in treatment of chronic inflammatory bowel disease.

Uptake and excretion of vecuronium bromide and pancuronium bromide in the isolated perfused rat liver.

Using the isolated perfused rat liver preparation, the disappearance from the perfusate and the excretion in the bile of vecuronium bromide and pancuronium bromide and their metabolites were followed for 2 h after the addition of 1 mg of either drug to the perfusate. In addition, the rate of change of the hepatic content of these two compounds was calculated by serially subtracting the amount of the compound and the metabolites in the bile and in the perfusate from the dose of drug added to the perfusate. It was found that, whereas the concentration of pancuronium in the perfusate declined slowly and monoexponentially, vercuronium concentration in the perfusate declined rapidly in a biexponential manner. No metabolites of either drug were detected in the perfusate. Approximately 40% of the injected dose of vecuronium was excreted in the bile as unchanged vecuronium and another 30% as the 3-hydroxy metabolite. No other metabolites of vecuronium were found in the bile. In total only about 7% of pancuronium (unchanged) was collected in the bile by the end of the experiment. It is concluded that, in comparison to pancuronium, the rat liver takes up large amounts of vecuronium rapidly, half of which is eliminated as unchanged vecuronium and half as the 3-hydroxy derivative. A small amount of vecuronium or its 3-hydroxy metabolite is returned to the perfusate from the liver. Some possible mechanisms underlying these differences are discussed.

Pharmacokinetics and disposition of pipecuronium bromide in the cat.

The pharmacokinetics and hepatic disposition of pipecuronium have been investigated in cats with normal and absent renal function. A combined fluorimetric and chromatographic technique was used to determine the concentrations of pipecuronium and its metabolites in the samples. Following intravenous injection of 150 micrograms kg-1, pipecuronium disappeared from the plasma bi-exponentially with half-lives of 9.8 +/- 5.4, 77.7 +/- 9.7 min and 7.2 +/- 5.0, 100, 6 +/- 23.7 min; the Vd was 362.3 +/- 74.9 ml kg-1 and 123.7 +/- 14.6 ml kg-1 and the clearance was 5.0 +/- 0.9 ml min-1 kg-1 and 1.0 +/- 0.1 ml min-1 in the animals with and without renal function, respectively. In the animals with normal kidney function 53%, 12% and 8% of the administered dose of pipecuronium were recovered within 8 h in the urine, bile and liver, respectively. In 'nephrectomized' cats the lack of renal elimination was to a great extent compensated for by increased hepato-biliary elimination. Absence of renal function significantly altered the pharmacokinetic parameters and prolonged the time-course of the neuromuscular blocking effects of pipecuronium. Neither temporary hepatic exclusion nor intraportal administration of pipecuronium indicated any significant role of the liver in handling pipecuronium. Renal excretion seems to be the predominant route of elimination. No metabolites were found in this study.

Pharmacokinetics and pharmacodynamics of vecuronium and pancuronium in anesthetized children.

The pharmacokinetics and pharmacodynamics of vecuronium and pancuronium were determined in 12 children (3-6 yr) undergoing minor surgery under 60% nitrous oxide, 1 MAC halothane anesthesia. When the level of anesthesia and the electromyograph (EMG) recording of the adductor pollicis were stable, an intravenous bolus of vecuronium (100 micrograms/kg) or pancuronium (100 micrograms/kg) was administered. Plasma concentrations of the two muscle relaxants were determined for 6 hr after the administration by means of a fluorimetric assay followed by a thin layer chromatography. Plasma concentrations of vecuronium and pancuronium declined biexponentially in children and no metabolites could be detected in plasma. The elimination half-lives of vecuronium and pancuronium did not differ significantly. The volume of distribution at steady state (Vdss) was greater (P less than 0.05) after vecuronium (320 +/- 181 ml/kg; mean +/- SD) than after pancuronium (203 +/- 36 ml/kg). Plasma clearance of vecuronium (2.8 +/- 0.9 ml X min-1 X kg-1) was greater than that of pancuronium (1.7 +/- 0.2 ml X min-1 X kg-1; P less than 0.05). Plasma concentrations measured at 10%, 50%, or 90% recovery of the EMG response did not differ significantly for vecuronium and pancuronium. Thus the shorter duration of action of vecuronium is probably due to its greater apparent volume of distribution, as well as to its higher plasma clearance. Thus although the elimination half-lives are comparable, the plasma disappearance of vecuronium is more rapid than that of pancuronium.

Comparative pharmacokinetics and dynamics of vecuronium and pancuronium in anesthetized patients.

Plasma concentrations and the degree of neuromuscular blockade after a 2-min infusion of 0.1 mg/kg of vecuronium bromide or pancuronium bromide (equipotent doses) were studied in 12 gynecologic patients. The plasma concentrations of both drugs declined in a triphasic manner. The difference between the intercepts and rate constants of the two drugs was not significant. Vecuronium was removed faster from the plasma than pancuronium; this was reflected in a significantly larger plasma clearance rate for vecuronium (4 ml X min-1 X kg-1 vs 1.1 ml X min-1 X kg-1 for pancuronium). The effective plasma concentrations at 50% recovery of the twitch height were 0.11 +/- 0.02 (vecuronium) and 0.2 +/- 0.03 microgram/ml (pancuronium). The disposition kinetics were adequately described by a three-compartment model. An effect compartment was added to the model to correlate the neuromuscular effects and plasma concentrations of both drugs. The ratio between concentrations of vecuronium and pancuronium in the effect compartment at 50% twitch height was 0.83. In spite of its greater potency, vecuronium has a shorter duration of action than pancuronium.

Disposition and urinary excretion of vecuronium bromide in anesthetized patients with normal renal function or renal failure.

The effect and plasma concentrations of vecuronium bromide were measured in normal patients after an intravenous dose of 50, 100, or 150 micrograms/kg and in patients with renal failure after 50 or 100 micrograms/kg. Urinary excretion of vecuronium was studied in normal patients after the 150 micrograms/kg dose. Pharmacokinetic parameters of patients with or without renal failure were similar. No metabolites of vecuronium were found in the plasma. Twenty percent of vecuronium was excreted unchanged in the urine; 5% as the 3-hydroxy derivative. No other metabolites of vecuronium were found in the urine. Increasing doses of vecuronium shortened the onset, but prolonged the duration of action and the recovery rate, to a similar extent in patients with or without renal failure. It was concluded that the disposition of vecuronium was best described by a three compartment model. Both the disposition and the effect of vecuronium are only marginally disturbed by renal failure.

Disposition of vecuronium bromide in the cat.

The disposition of vecuronium bromide has been investigated in six normal cats (group I) and in six cats with ligated renal pedicles (group II). A combined fluorimetric and chromatographic technique was used to determine the concentrations of vecuronium and its metabolites in biological material. After i.v. injection of 0.6 mg kg-1, vecuronium disappeared rapidly from the plasma of the normal cat. Concentrations decreased bi-exponentially with half-lives of 4.6 and 31 min, respectively. The steady state volume of distribution was 0.23 litre kg-1 and the clearance 11 ml min-1 kg-1. Seventy percent of an i.v. dose of vecuronium (or its metabolites) was recovered: 15% in the urine, 40% in the bile and 15% in the liver. Only 3.8% of this consisted of the 3-hydroxy metabolite. There were no significant differences in pharmacokinetic data or in the amounts of vecuronium and its metabolites recovered in cats with ligated renal pedicles. The 15% of vecuronium normally excreted by the kidney was compensated for by increased hepatic and biliary concentration of vecuronium.

Pancuronium pharmacokinetics in patients with liver cirrhosis.

The serum and urinary concentrations of pancuronium were measured in 14 surgical patients with cirrhosis and 12 patients free from liver disease undergoing abdominal surgery. A two-compartment open model was used in the pharmacokinetic analysis of the data. A two-fold increase in both the distribution half-life (T 1/2 alpha) from 11 min to 24 min and in the elimination half-life (T 1/2 beta) from 114 min to 208 min was observed in patients with cirrhosis. In these individuals, the total apparent volume of distribution of pancuronium was increased by 50%. Plasma clearance of pancuronium was decreased by 22%. No significant difference was found in the urinary excretion and biotransformation pattern of pancuronium. These results suggest that there is a risk of prolonged duration of action of pancuronium in patients with cirrhosis. In these patients, the initial dose to achieve adequate muscle relaxation is high and simultaneously there is slow disappearance of pancuronium from plasma. These alterations are mainly a consequence of the increase in the distribution volume of pancuronium in patients with cirrhosis.

The comparative potency and pharmacokinetics of pancuronium and its metabolites in anesthetized man.

To determine the potency of pancuronium and its metabolites, 3-OH-, 17-OH- and 3,17-OH-pancuronium, cumulative dose-response curves were determined in five anesthetized patients with each drug. Pancuronium (ED50 = 0.041 mg/kg) was 2 times more potent than 3-OH-pancuronium (ED50 = 0.082 mg/kg), 50 times more potent than 17-OH-pancuronium (ED50 = 2.0 mg/kg) and 54 times more potent than 3,17-OH--pancuronium (ED50 = 2.15 mg/kg). In 21 other patients, one equipotent dose of either pancuronium or one of its metabolites was given as an i.v. bolus. Onset time and duration of neuromuscular blockade from 3-OH- and 3,17-OH-pancuronium did not differ significantly from that of pancuronium; 17-OH-pancuronium had a shorter duration of action than did pancuronium. Although pancuronium tended to have a slightly longer elimination half-life, the pharmacokinetics of the four drugs did not differ significantly. The elimination half-lifes were 110, 68, 73 and 71 min for pancuronium and its 3-OH, 17-OH and 3,17-OH derivatives, respectively. We conclude that although pancuronium is more potent than its 3-OH, 17-OH and 3,17-OH metabolites, the pharmacokinetics of these three metabolites do not differ from each other and from that of pancuronium.

A preliminary investigation of the renal and hepatic excretion of gallamine triethiodide in man.

The fate of gallamine triethiodide has been investigated in patients undergoing cholecystectomy with choledochostomy (group I), pelvic operations (group II) and orthopaedic operations (group III). Following a single i.v. injection of gallamine 2.5 mg kg(-1) the disappearance of the drug from the serum occurred in three phases with half-lives of less than 5, 30, 138 min, less than 5, 39, 141 and less than 5, 48, 144 min in the respective groups. Twenty-four hours after injection the renal excretion of the unchanged drug was 53% (15-100%) of the administered dose in group I, 67% (40-90%) in group II and 95% (89-100%) in group III. The biliary excretion of gallamine appeared to be negligible in man. The relationship between renal excretion and duration of action of gallamine, and the influence of some intraoperative factors on drug disposition, are discussed.