Antimuscarinic premedication in canine anaesthesia: a comparison of atropine, hyoscine and glycopyrrolate

Anticholinergic drugs are commonly given as preanaesthetic medication to reduce secretions and bradycardia. In this trial, clinical cases were given atropine, hyoscine or glycopyrrolate on a logarithmic dose scale. Another group was not given any anticholinergic agent. Anaesthesia was induced with thiopentone and maintained with halothane in oxygen and nitrous oxide. All the anticholinergic drugs decreased salivation although there was also a small fall in salivation in the control group. Pulse rates rose on induction and fell over the course of anaesthesia in the control group but the mean pulse rates did not fall below the normal range. Atropine and hyoscine produced a tachycardia followed by a fall in pulse rate similar to the control group during anaesthesia. Glycopyrrolate maintained the pulse at the same level throughout. In view of the disadvantages of tachycardia, glycopyrrolate is probably the anticholinergic agent of choice when such a drug is indicated.     

Depth of anaesthesia

One hundred and fifty years after the first general anaesthetic in 1846 our knowledge about the mechanisms of general anaesthetics is still very sparse. The concept ‘depth of anaesthesia’ was introduced by John Snow (1847). He described ‘5° of narcotism’. Because one single agent had to provide all the components of general anaesthesia, the main problem for the anaesthetist was to avoid morbidity and mortality associated with excessively deep anaesthesia. The introduction of curare in 1942 allowed muscle relaxation required for surgery during a lighter level of anaesthesia, but also changed the emphasis from the problem of too deep anaesthesia and death, to too light anaesthesia and litigation. The problem of awareness during general anaesthesia with muscle relaxants provided the main impetus for monitoring depth of anaesthesia. During daily clinical practice the anaesthesiologist relies on clinical signs to evaluate anaesthetic depth, although several studies have shown a poor correlation between the 2 (Cullen et al. 1972; Evans and Davies 1984; Russell 1993). Different methods have been used in attempts to measure anaesthetic depth (Evans and Davies 1984; Stanski 1994), but none have been developed to a state where they can be used routinely in the operating theatre. This review will cover some of the parameters used to evaluate anaesthetic depth.     

Cardiovascular Effects of Amphetamine in the Horse

Each of nine horses was treated with amphetamine alone, with atropine alone, and with amphetamine and atropine in combination. Cardiac effects of these drugs were studied by electrocardiography during resting and exercising states and immediately after exercise.

Although each treatment increased heart rate significantly during the resting state, only the amphetamine plus atropine treatment increased heart rate significantly during exercise. Decrease in heart rate immediately after exercise differed significantly for each treatment; the most rapid decrease in heart rate was found after the amphetamine treatment.

Amphetamine caused second-degree atrioventricular (AV) block in each horse during the postexercise period. Amphetamine also caused ectopic beats either during or immediately after exercise in six horses. Second-degree AV block was not found when atropine was used alone or when used in combination with amphetamine. Fewer ectopic beats were found when atropine was used with amphetamine.

Heart rate responses indicated that the direct effect of amphetamine was greater than the reflex effect at rest and during exercise; the opposite was true during postexercise. Second-degree AV block during the postexercise period was attributed to vagotonia due to baroreceptor stimulation. Release of norepinephrine by amphetamine probably caused many of the ectopic beats by increasing automaticity of subordinate pacemakers.

     

Comparison of the arterial blood gas,arterial oxyhaemoglobin saturation and end-tidal carbon dioxide tension during sevoflurane or isoflurane anaesthesia in rabbits

The effects of sevoflurane or isoflurane on arterial blood gas, arterial oxyhaemoglobin saturation and end-tidal CO2 tension were monitored during induction and maintenance of anaesthesia in 10 premedicated New Zealand White (NZW) rabbits.For induction, the anaesthetic agents were delivered via a face-mask. After induction was completed, an endotracheal tube was introduced for maintenance of anaesthesia for a period of 90 minutes. Changes in heart rate, respiratory rate, arterial blood gas, arterial oxyhaemoglobin saturation, blood pH and end-tidal CO2 tension were recorded. Although sevoflurane and isoflurane produce similar cardiopulmonary effects in premedicated rabbits, sevoflurane provides a smoother and faster induction because of its lower blood/gas partition coefficient. Thus sevoflurane is probably a more suitable agent than isoflurane for mask induction and maintenance. Its lower blood solubility also makes sevoflurane more satisfactory than isoflurane for maintenance of anaesthesia because it allows the anaesthetist to change the depth of anaesthesia more rapidly.     

Significance of the oculocardiac reflex during ophthalmic surgery in the dog

Antimuscarinic drugs were intentionally excluded from the anaesthetic protocol used in 72 dogs undergoing a variety of ophthalmic surgical procedures. Following premedication with acepromazine and morphine, anaesthesia was induced with thiopentone and maintained with halothane vaporised in oxygen and nitrous oxide. Muscle relaxation was achieved in all dogs using either vecuronium or atracurium and ventilation was controlled to produce mild hypocapnia. Only one patient showed electrocardiographic and arterial blood pressure changes that could be attributed to the oculocardiac reflex. This indicates that the reflex is of minor clinical importance when anaesthesia results in good muscle relaxation, mild hypocapnia and adequate unconsciousness. When these conditions are present the routine use of atropine or glycopyrrolate is unwarranted during ocular surgery in the dog.     

The parasympatholytic effects of atropine sulfate and glycopyrrolate in rats and rabbits.

Nine groups of rats (n = 5 per group) received an intramuscular (IM) injection of one of the following drugs or drug combinations: saline, atropine (0.05 mg/kg), glycopyrrolate (0.5 mg/kg), ketamine:xylazine (85:15 mg/kg), ketamine:detomidine (60:10 mg/kg), atropine:ketamine:xylazine (0.05: 85:15 mg/kg), glycopyrrolate: ketamine:xylazine (0.5:85:15 mg/kg), atropine:ketamine:detomidine (0.05: 60:10 mg/kg) or glycopyrrolate: ketamine:detomidine (0.5:60:10). Similarly six groups of rabbits (n = 5) received an IM injection of either saline, atropine (0.2 mg/kg), atropine (2 mg/kg), glycopyrrolate (0.1 mg/kg), ketamine:xylazine (35:10 mg/kg) or glycopyrrolate:ketamine:xylazine (0.1:35:10 mg/kg). In rats, atropine sulfate (0.05 mg/kg) and glycopyrrolate (0.5 mg/kg) produced an increase in heart rate for 30 and 240 min, respectively. In rabbits atropine sulfate at either 0.2 or 2.0 mg/kg did not induce a significant increase in heart rate, but glycopyrrolate (0.1 mg/kg) elevated the heart rate above saline treated animals for over 50 min. Both atropine and glycopyrrolate provided protection against a decrease in heart rate in rats anesthetized with ketamine: xylazine (85:15 mg/kg) or ketamine: detomidine (60:10 mg/kg); however, glycopyrrolate was significantly more effective in maintaining the heart rate within the normal range. Glycopprrolate also prevented a decrease in heart rate in rabbits anesthetized with ketamine:xylazine (35:5 mg/kg). Neither glycopyrrolate nor atropine influenced respiration rate, core body temperature or systolic blood pressure when used alone or when combined with the injectable anesthetic. Glycopyrrolate is an effective anticholinergic agent in rabbits and rodents and more useful as a preanesthetic agent than atropine sulfate in these animals.     

Does the A-line ARX-lndex provide a reasonable assessment of anaesthetic depth in dogs undergoing routine surgery?

The monitoring of anaesthetic depth is usually based on the subjective assessment of the patient. An objective assessment of anaesthesia has only recently become possible. The auditory-evoked response has predictable changes in response to increasing doses of anaesthetic agents. Recent advances have brought about a regression model with exogenous input of the auditory-evoked response, the A-line ARX-Index (AAI Index). The AAI Index is a dimensionless number between 0 and 100. This technology has been incorporated into the AEP (auditory-evoked potential) monitor that is utilised to assess anaesthetic depth in humans. This study was undertaken to determine if the AEP monitor was useful in dogs. Ten dogs were enrolled in the study. After a full clinical and otoscopic examination, dogs were premedicated with acetylpromazine and morphine. Anaesthesia was induced with thiopentone and maintained with halothane. End-tidal carbon dioxide, temperature, pulse oximetry, blood pressure and the electrocardiogram were monitored and recorded every 5 minutes. Anaesthetic depth was assessed as either being adequate or inadequate by the anaesthetist during surgery. An AEP monitor was attached to the patient and automatically collected AAI Index data. The anaesthetist was blinded to the AEP monitor. Following the completion of the surgical procedure, the patient was allowed to wake up with the AEP monitor attached. The AAI Index was analysed to compare adequate with inadequate anaesthesia during the period of surgery and awake with sleep data during recovery. All AAI Index values associated with inadequate anaesthesia were greater than 31 while adequate values were less than 35. The difference between the groups was statistically significant and the power was 0.97. Statistically, the awake and sleep values were significantly different with a power of 0.99. From this study it can be concluded that the AAI Index shows good prospect for the evaluation of anaesthetic depth in dogs undergoing surgery. A larger study is needed to confirm these results.     

Anticholinergic medication in the dog before and during anesthesia

In clinical studies in dogs of all categories of age, which were predicted for surgical purposes under a combination anaesthesia with Fluanisone/Fentanyl/Nitrous oxide/Halothane, investigations after treatment with atropine or glycopyrrolate were performed. In experimental studies investigations about heart-rate and heart work (rate-pressure-product RPP) under different injection anaesthesia-methods (Fluanisone/Fentanyl/Metomidate, Climazolam/Fentanyl, Xylazine/l-Methadone) are performed. In the clinical studies many of the dogs produce elevated heart-rates after anticholinergic premedication. After special indicated treatment of dysrhythmias with glycopyrrolate or atropine in all cases normorhythmia can be achieved. An increase in heart rate during awaking time can be seen in non premedicated as well as in anticholinergic treated animals for a short period of time. In the experimental studies the anticholinergic treatment leads to increased heart rate and/or elevated arterial pressure, which produce an enormous increase in the rate pressure product and oxygen consumption. In conclusion a general anticholinergic premedication can not be recommended. Its use should be special indicated for bradycardia and/or dysrhythmias in the sense of AV-conduction disturbances.     

A preliminary trial comparison of several anesthetic techniques in cats

The aim of this study was to investigate the effect of several drug combinations (atropine, xylazine, romifidine, methotrimeprazine, midazolam, or fentanyl) with ketamine for short term anesthesia in cats. Twelve cats were anesthetized 6 times by using a cross-over Latin square protocol: methotrimeprazine was combined with midazolam, ketamine, and fentanyl; midazolam and ketamine; romifidine and ketamine; and xylazine and ketamine. Atropine was combined with romifidine and ketamine, and xylazine and ketamine. Temperature, heart rate, and respiratory rate decreased in all groups. Apnea occurred in 1 cat treated with methotrimeprazine, romifidine, and ketamine, suggesting that ventilatory support may be necessary when this protocol is used. Emesis occurred in some cats treated with alpha 2-adrenoceptor agonists, and this side effect should be considered when these drugs are used.     

The Photomotor Reflex as an Indicator of Consciousness in the Immobilized Dog

Abstract— When a relaxant is used in conjunction with light general anaesthesia, it is not possible to distinguish between true unconsciousness, and consciousness masked by immobilization, by the usual reflexes involving voluntary muscle. Experiments are described which show that the photo-motor reflex (contraction of the pupil of the eye with increase in intensity of light stimulus), unlike the other reflexes commonly used for testing anaesthesia, gave a reliable indication of returning consciousness in a dog immobilized by a relaxant. The reflex was not affected by premedication with atropine, provided that the dose of atropine did not exceed 0.032 mg./kg. body-weight. The reflex is valid when anaesthesia is induced by barbiturate alone, or by a combination of barbiturate and ether.     

Overdose during chemical restraint in a black rhinoceros (Diceros bicornis)

A juvenile female black rhinoceros (Diceros bicornis) was successfully treated after overdose of drugs used for chemical restraint. Subsequent general anaesthesia for surgical reduction of a recurrent rectal prolapse was uneventful. Over a 25-minute period before transportation to the veterinary hospital, the animal received a total dose of 1.225 mg etorphine, 30 mg acepromazine and 30 mg detomidine. Based on an estimated mass of 200 kg, these corresponded to doses of 6.1 microg kg(-1) etorphine, 150 microg kg(-1) acepromazine, and 150 microg kg(-1) detomidine which constitutes considerable overdose for each drug given separately, notwithstanding the synergy that probably resulted when the three drugs were present concurrently. The estimated body mass may have substantially overestimated the actual body mass and exacerbated overdosage. The animal was recumbent and apnoeic on arrival at the hospital. Heart sounds were auscultated and a weak peripheral pulse was palpated; no pulse deficits were detected, although the heart rate was low. The trachea was intubated, inspired breath was enriched with oxygen and the lungs ventilated manually. Diprenorphine (1.5 mg) was given intravenously and spontaneous breathing resumed 11 minutes later. After induction of general anaesthesia using isoflurane, emergency surgery for correction of rectal prolapse was performed, from which the animal recovered uneventfully. The case highlights some of the practical problems that may be encountered in dealing with dangerous and unfamiliar species.     

Clinical observations on the use of the muscle relaxant atracurium in the dog

The use of the new neuromuscular blocking agent, atracurium besylate, is described in 22 dogs undergoing a variety of surgical procedures under general anaesthesia. An initial dose of 0.5 mg/kg proved effective and produced a block of 40 min duration. Incremental doses of 0.2 mg/kg were used. Reversal of the neuromuscular block by neostigmine preceded by atropine was rapid and effective. No untoward side-effects were observed with this drug.     

Activation procedures in the electroencephalograms of healthy and epileptic cats under propofol anaesthesia

The current study evaluated the diagnostic value of electroencephalographic recordings (EEG) in cats with epilepsy under special consideration of photic stimulation and hyperventilation. EEGs in six healthy cats were recorded under light (mean dose of 0.23 mg/kg/min) and deep (mean dose of 0.7 mg/kg/min) propofol anaesthesia, whereas EEGs in 13 diseased cats were recorded under a propofol anaesthesia which was kept as light as possible (mean dose of 0.39 mg/kg/min). Paroxysmal discharges were detected in six of 13 cats suffering from seizures (two cats with idiopathic epilepsy and four cats with symptomatic epilepsy). Activation techniques did not enhance the diagnostic value of the EEGs. Photic driving was detected in one of six healthy cats under light, in five of six healthy cats under deep propofol anaesthesia and in 11 of 13 cats with seizures. Systematic use of activation techniques does not seem to increase the diagnostic yield of the recorded EEGs and should not be used in a clinical setting until future studies indicate value. Further investigations into the origin of photic driving under propofol anaesthesia are needed and could lead to the development of a reliable animal model to research into drug effects on the EEG.     

A comparison of endotracheal and intravenous routes for atropine administration in anaesthetised dogs

The endotracheal route for atropine administration was compared with the intravenous route in 50 anaesthetised dogs. The response to drug administration was recorded as the change in heart rate from a steady pretreatment value. An indication was found of a positive relationship between the dose and the response to atropine given endotracheally. The increase in heart rate following atropine administration was similar, in terms of magnitude and speed of onset, when given by the endotracheal route at 0–06 mg/kg, as compared with that obtained by the intravenous administration of atropine at 0–04 mg/kg (P<0–05).     

The use of hyoscine N-butylbromide to treat intraoperative bradycardia during isoflurane anaesthesia in three horses

Intraoperative bradycardia is not an uncommon complication in anaesthetised horses and it has been recommended that severe bradycardia (defined as heart rate (HR) <25 beats/min) during general anaesthesia, when associated with hypotension (mean arterial pressure (MAP) <70 mmHg) and other signs of inadequate tissue perfusion, should be treated with anticholinergics. Muscarinic antagonists, such as atropine and glycopyrrolate, cause positive chronotropism and dromotropism (improved atrioventricular conduction) by competitively blocking the effects of acetylcholine at muscarinic receptors in the heart. However, in horses, prolonged intestinal hypomotility and colic have been associated with the use of atropine and glycopyrrolate which has led to the investigation of the use of hyoscine N-butylbromide (hyoscine NBB) to treat alpha 2 agonist-induced bradycardia in horses. This report describes the successful use of hyoscine NBB to treat symptomatic intraoperative bradycardia in three isoflurane-anaesthetised horses.     

Clinical effects of detomidine with or without atropine used for arthrocentesis in horses

The effectiveness of detomidine with or without atropine sulfate premedication in producing sedation and analgesia for arthrocentesis was studied in 12 horses. The effects were evaluated by monitoring heart and respiratory rates, borborygmi, distance from the lower lip to the floor, systolic blood pressure, and response to needle insertion. Either atropine or saline (as a placebo) was administered immediately prior to detomidine. All drugs were administered intravenously. Measurements were taken prior to drug injection and at 1, 5, 10, 15, 20, 25, 30, 40, 50, 60, 120, 180 and 240 minutes postinjection. Detomidine with atropine resulted in significantly higher heart rates than detomidine without atropine for the three hours of observation. Borborygmi were significantly decreased for four hours following detomidine with atropine and for three hours following detomidine without atropine, when compared to preinjection levels. Systolic blood pressure was significantly increased for 15 minutes following detomidine and atropine compared to the preinjection level. The head was markedly lowered for 60 minutes with either treatment. Atropine prevented the bradyarrhythmia and bradycardia induced by detomidine, but it induced a tachycardia. A satisfactory response for needle insertion and adequate synovial fluid aspiration was achieved in 95% of the trials with detomidine, with or without atropine sulfate premedication. The results suggest that, although atropine prevents bradyarrhythmia and bradycardia following detomidine, administering detomidine without atropine is satisfactory for arthrocentesis in untrained horses.     

Autonomic and Cardiovascular Effects of Neuromuscular Blockade Antagonism in the Dog

Autonomic and cardiovascular changes were studied when neuromuscular blockade was antagonized in 96 dogs with one of eight anticholinesterase-antimuscarinic drug combinations. Neostigmine (50 or 100 micrograms/kg) was administered before or after atropine (40 micrograms/kg) or glycopyrrolate (10 micrograms/kg). The high dose of neostigmine (100 micrograms/kg) caused bradyarrhythmias, salivation, and signs of bronchosecretion when used with either antimuscarinic agent and irrespective of the administration sequence. The heart rate increased, but not significantly, when atropine was injected before either dose of neostigmine. This did not occur when this administration sequence was reversed. Arrhythmias and cardiovascular and autonomic changes did not occur when glycopyrrolate was injected before or after neostigmine at 50 micrograms/kg.     

The Effects of Atropine and Glycopyrrolate on Heart Rates in Conscious Mature Goats

The effects of intravenously administered atropine (0.2 mg/kg) and glycopyrrolate (0.01 mg/kg) on heart rate were studied in 10 conscious mature goats. In a drug cross-over fashion, either atropine, glycopyrrolate, or 0.9% saline solution was administered using the same volume (0.05 mL/kg). Atropine and glycopyrrolate caused a significant increase in heart rate ( P <.05), whereas saline solution (0.09%) did not. The mean percent changes in heart rate from baseline were similar for atropine and glycopyrrolate up to 14 minutes after administration. Thereafter, glycopyrrolate had a significantly greater mean change in heart rate than atropine, ie, up to 29 minutes ( P <.05). Within the atropine group, the mean percentage changes in heart rate became significantly lower compared with the initial increase (1 minute) starting at 11 minutes. For the glycopyrrolate group, the mean percent changes became significantly lower starting at 27 minutes. Glycopyrrolate and atropine had a mean percentage change in heart rate of greater than 1.0%, up to 31 and 22 minutes, respectively. At the doses used, glycopyrrolate had longer duration of action than atropine but the magnitude of increase was similar.     

Fentanyl‐induced asystole in two dogs

Fentanyl is used in small animals for perioperative analgesia during anaesthesia. Severe bradycardia and asystole were observed on bolus administration of a 3 µg/kg loading dose of fentanyl in two dogs under isoflurane anaesthesia. Premedication with 10 µg/kg glycopyrrolate did not prevent asystole in the first case; and although bradycardia was treated with 5 µg/kg glycopyrrolate administered intravenously in the second case, the heart rate continuously decreased and asystole subsequently developed. Asystole in both cases was quickly corrected by intravenous administration of 0 · 04 mg/kg atropine and closed chest compressions. This case report describes asystole induced by fentanyl administration in isoflurane anaesthetised dogs. Atropine was more effective than glycopyrrolate in the treatment of fentanyl‐induced asystole.