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PubMed1979

Effect of tetrahydroaminoacridine and 4-aminopyridine on recovery from ketamine-diazepam anesthesia in the macacus rhesus monkey.

Tetrahydroaminoacridine (T.H.A., Tacrine) 1 mg/kg, and 4-aminopyridine (Pymadin) 0.2 and 1.0 mg/kg i.v., significantly reduced the recovery time when the were administered after ketamine-diazepam anesthesia in Maccacus Rhesus monkeys. Anesthesia was induced with ketamine (50 mg), diazepam (1.2 mg) and sodium glycopyrrolate (0.02 mg) as a secretiondrying agent, as a single bolus injection. Anesthesia was continued with ketamine by constant infusion of a solution of 5 mg/ml, at a speed of 20 mg/ml, at a speed of 20 ml/hour, during 30 minutes. The 5 monkeys in the control group were allowed to recover spontaneously. The test series consisted of the same monkeys, with an adequate rest period of one or more weeks between anesthesias. Recovery was indicated by production of nystagmus, and by an awake pattern in the EEG. Clinical signs, restlessness and purposeful movements, were also used.

4-Aminopyridine↗

PubMed1992

Inotropic mechanisms of dopexamine hydrochloride in horses.

Mechanisms responsible for the positive inotropic effects of dopexamine were investigated in 8 halothane-anesthetized horses. The hemodynamic effects of increasing infusions of dopexamine (5, 10, 15 micrograms/kg of body weight/min) were determined before and after sequential administration of specific antagonists. Using glycopyrrolate and chlorisondamine, and atenolol and ICI 118,551, muscarinic and nicotinic ganglionic, and beta 1, and beta 2-adrenergic receptor blockade, respectively, was induced. Dopexamine infusions induced increase in heart rate, cardiac output, systolic and mean arterial blood pressure, and maximal rate of left ventricular pressure development (+dP/dtmax). Right atrial pressure and systemic vascular resistance decreased. Parasympathetic and ganglionic blockade attenuated cardiac output, systolic and mean aortic blood pressures, and +dP/dtmax responses to dopexamine infusion. Dopexamine-induced increase in heart rate was potentiated by parasympathetic and ganglionic blockade. beta 1-Adrenergic receptor blockade decreased heart rate, cardiac output, arterial blood pressure, and +dP/dtmax from baseline values and markedly reduced the response to dopexamine infusion. beta 2-Adrenergic receptor blockade induced further decrease in hemodynamic variables from baseline values and completely abolished the cardiostimulatory effects of dopexamine on +dP/dtmax. These data indicate that baroreflex activity, beta 1- and beta 2-adrenergic receptor stimulation may be an important cause of dopexamine's positive inotropic effects in horses.

Adrenergic Agonists↗

PubMed1992

Anesthesia for temporomandibular arthroplasty in a quadriplegic patient: a case report.

A 41-year-old male quadriplegic patient with bilateral TMJ ankylosis was admitted for surgery under general anesthesia. Preoperative tests showed abnormal lung function and a low total serum calcium level. Premedication consisted of diazepam 10 mg orally and glycopyrrolate 0.2 mg intramuscularly 90 minutes before the start of the operation. Because of an inability to open the mouth more than 0.5 cm, a nasal fiberoptic endoscopic intubation was done under sedation and local anesthesia. For maintenance of anesthesia the patient received nitrous oxide 50% in oxygen, halothane, and alfentanil. No muscle relaxant was administered. The 2-hour operation was completed uneventfully and the patient needed no ventilatory support afterward. Major anesthetic problems of spinal injury patients can be compared to those with cervical cord transection. The stage that the condition has reached determines the dominant anesthetic problems. The chronic stage (greater than 3 months postinjury, as in this patient) is usually characterized by sympathetic overactivity. Anesthetic problems during this stage may include risk of hyperkalemia from succinylcholine, cardiovascular instability and autonomic hyperreflexia, impaired thermoregulation, anemia, chronic infections, risk of hypercalcemia, and alveolar hypoventilation. None of these problems was encountered in this patient. A surprising finding was that the low serum calcium concentration did not influence the anesthetic outcome.

Adult↗

PubMed1992

Yohimbine/flumazenil antagonism of hemodynamic alterations induced by a combination of midazolam, xylazine, and butorphanol in dogs.

Reversal of hemodynamic alterations induced by midazolam maleate (1.0 mg/kg of body weight), xylazine hydrochloride (0.44 mg/kg), and butorphanol tartrate (0.1 mg/kg) with yohimbine (0.1 mg/kg) and flumazenil (0.25 mg/kg) was evaluated in 5 dogs. The dogs were anesthetized with isoflurane for instrumentation. With return to consciousness, baseline values were recorded, and the midazolam/xylazine/butorphanol mixture with glycopyrrolate was administered IV. Hemodynamic data were recorded for 60 minutes, and then a reversal mixture of yohimbine and flumazenil was administered IV. All variables were measured 1 minute from beginning of the reversal injection. Mean arterial pressure, pulmonary arterial pressure, systemic vascular resistance, and right ventricular stroke work index increased significantly (P < 0.05) above baseline at 60 minutes. Cardiac index and central venous pressure significantly decreased below baseline at 60 minutes. After reversal, mean arterial pressure and central venous pressure significantly decreased from baseline, whereas cardiac index, pulmonary arterial pressure, and right ventricular stroke work index increased significantly above baseline. Heart rate, cardiac index, and right ventricular stroke work index increased significantly above the 60-minute value after reversal. Mean arterial pressure and systemic vascular resistance decreased significantly (P < 0.05) below the 60-minute value after reversal. The hemodynamic alterations accompanying midazolam/xylazine/butorphanol sedation-anesthesia may be rapidly reversed with a combination of yohimbine and flumazenil.

Anesthesia↗

PubMedDate not supplied

Bispectral Index System (BIS) monitoring reduces time to discharge in children requiring intramuscular sedation and general anesthesia for outpatient dental rehabilitation.

PURPOSE: Pediatric patients who receive both intramuscular (i.m.) sedation and general anesthesia (GA) for oral rehabilitation occasionally experience prolonged sedation and delayed discharge. The Bispectral Index System (BIS) is an EEG monitor that measures the level of sedation. The authors compared discharge times of patients who had BIS monitoring to those who did not to determine if the use of BIS speeded discharge. METHODS: After IRB approval, 20 children were enrolled. BIS was monitored continuously from admission until discharge. Each child received ketamine, midazolam, and glycopyrrolate i.m. Once sedated, the patient was transferred to the operating room, monitored, and i.v. access was established. GA proceeded with sevoflurane, rocuronium, and fentanyl. Randomly, in half the patients, the anesthesiologist knew and maintained the BIS at GA level of sedation by adjusting sevoflurane. In the rest, the anesthesiologist did not know BIS. Time from turning of sevoflurane to discharge was noted and compared. RESULTS: Patients where the BIS was known and used were discharged 60+/-13 minutes after the end of GA. Patients where BIS was unknown were discharged 90+/-11 minutes after the end of GA (P<.001). CONCLUSIONS: Based on the data, the authors recommend the use of BIS to facilitate faster discharge of pediatric patients who require i.m. sedation and GA for oral rehabilitation.

Adjuvants, Anesthesia↗

PubMed2004

Sialorrhea: a management challenge.

Sialorrhea (drooling or excessive salivation) is a common problem in neurologically impaired children (i.e., those with mental retardation or cerebral palsy) and in adults who have Parkinson's disease or have had a stroke. It is most commonly caused by poor oral and facial muscle control. Contributing factors may include hypersecretion of saliva, dental malocclusion, postural problems, and an inability to recognize salivary spill. Sialorrhea causes a range of physical and psychosocial complications, including perioral chapping, dehydration, odor, and social stigmatization, that can be devastating for patients and their families. Treatment of sialorrhea is best managed by a clinical team that includes primary health care providers, speech pathologists, occupational therapists, dentists, orthodontists, neurologists, and otolaryngologists. Treatment options range from conservative (i.e., observation, postural changes, biofeedback) to more aggressive measures such as medication, radiation, and surgical therapy. Anticholinergic medications, such as glycopyrrolate and scopolamine, are effective in reducing drooling, but their use may be limited by side effects. The injection of botulinum toxin type A into the parotid and submandibular glands is safe and effective in controlling drooling, but the effects fade in several months, and repeat injections are necessary. Surgical intervention, including salivary gland excision, salivary duct ligation, and duct rerouting, provides the most effective and permanent treatment of significant sialorrhea and can greatly improve the quality of life of patients and their families or caregivers.

Humans↗

PubMed1992

Clinical evaluation of the effects of ketamine sedation on pediatric dental patients.

This study was undertaken to determine the dosages, treatment times and side effects of ketamine HCI with and without two benzodiazepines when used for sedation on a group of precooperative children at the UCLA Children's Dental Center. Ketamine was evaluated when used alone, and in conjunction with two benzodiazepines, diazepam or a new water-soluble midazolam. An anti-muscarinic, atropine or glycopyrrolate, and nitrous oxide-oxygen were included in all sedations. Mean treatment times were increased significantly when ketamine and a benzodiazepine were used in combination. Additionally, mean ketamine dosages were decreased significantly when ketamine was utilized in combination with a benzodiazepine. All children tolerated the sedation well and there were no severe adverse reactions. Side effects included nausea, vomiting, and a rise in post-operative temperatures.

Anesthesia, Dental↗

PubMed2005

Paediatric organophosphate poisoning--a rural hospital experience.

OBJECTIVES: To document the presentation and course of organophosphate poisoning (OPP) in children and to record the frequency of atropine toxicity during treatment. DESIGN: A retrospective observational study was conducted of all recorded paediatric cases of OPP admitted to a regional hospital over a 5-year period from 1 June 1996 to 31 May 2001. SETTING: The study was conducted at Eben Donges Hospital, a regional hospital in the Boland/Overberg area of the Western Cape, where pesticide-intensive fruit farming remains the largest revenue generator. SUBJECTS. The study included all children aged 12 years or less (as per health services classification) with confirmed OPP. RESULTS: There were 23 patients. Most of the cases came from the De Doorns area (35%), with poisoning by ingestion accounting for 61% of cases. A distinct seasonal predominance was found that coincided with the summer harvest. Mode of presentation was variable and was not related to the initial pseudocholinesterase level. Evidence of atropine toxicity occurred in 8 of the 18 cases treated with atropine. No statistically significant risk factor was found for atropine toxicity. The average duration of hospitalisation was 5.05 days, with 2 children requiring transfer to tertiary facilities. CONCLUSIONS: The high number of referrals from a specific geographical area, combined with a 61% accidental ingestion rate, illustrates an area where legislation has failed to limit unnecessary exposure. Awareness of the seasonal predominance could prove pivotal to the success of future preventive strategies. Initial presentation and serum pseudocholinesterase levels did not correlate with duration of stay. The decision to transfer to a tertiary facility should only be explored once the patient has been stabilised with atropine. Atropine treatment is effective but carries a risk of toxicity. Glycopyrrolate may constitute an alternative treatment option.

Agriculture↗

PubMed2006

Preparation and biological effects of pure stereoisomeric novel soft anticholinergics.

A series of pure stereoisomeric soft glycopyrrolate analogues 3, 4 and 5 was synthesized using chiral intermediates and by careful separation of the stereoisomers formed during the last quaternization step of the synthesis. The stereochemistry of the products was elucidated using various 1D and 2D NMR techniques. Anticholinergic activity of the new compounds was determined by receptor binding studies and performing tests on isolated organs and by in vivo tests. Receptor binding revealed that in the higher alkyl ester series the (2R, 1'R, 3'R) and the (2R, 1'S, 3'S) isomers were the compounds showing the highest receptor affinity furthermore it demonstrated the confines of the length of the alkyl chain. In vitro isolated organ experiments correlated well with the receptor binding results, and in vivo investigations indicated the soft character of the compounds.

Animals↗

PubMed1991

Anesthetic and hemodynamic effects of dexmedetomidine during isoflurane anesthesia in a canine model.

Dexmedetomidine, an alpha 2-adrenergic agonist, was administered during isoflurane anesthesia to investigate its anesthetic sparing and hemodynamic effects in the canine model. Eleven healthy dogs were anesthetized with isoflurane, intubated, and allowed to breathe spontaneously. The animals were instrumented in order to measure or calculate mean arterial blood pressure (MABP), heart rate (HR), left ventricular end diastolic pressure (LVEDP), cardiac output (CO), and systemic vascular resistance (SVR). Isoflurane minimum alveolar concentration (MAC), baseline hemodynamic measurements, and plasma catecholamine levels were determined. A 20 micrograms/kg bolus of dexmedetomidine was injected intravenously (IV) and MAC and hemodynamic values were redetermined. When isoflurane requirements were 33% of baseline, isoflurane was returned to 90% MAC and the alpha 2-antagonist, atipamezole, was administered. All dogs were treated with 40 micrograms/kg glycopyrrolate throughout the experiment to prevent any bradycardic response. Dexmedetomidine reduced isoflurane MAC by 86%. SVR, MABP, and LVEDP were significantly increased while CO and catechloamine levels were reduced. Atipamezole fully reversed the reduction in anesthetic requirements. MABP and catecholamine levels returned to baseline. SVR and LVEDP increased while CO decreased. The dogs exhibited a profound reduction in anesthetic requirement, reduced catecholamine levels, and changes in hemodynamic parameters with dexmedetomidine administration. The anesthetic sparing effect appears to be mediated by the alpha 2-receptor, since atipamezole reversed the reduction in MAC. Hemodynamic changes may be species or dose related, or due to differences in existing sympathetic tone. The role of dexmedetomidine warrants further study as an adjunct anesthetic agent.

Adrenergic alpha-Agonists↗

PubMedDate not supplied

Oral ketamine for deep sedation of difficult-to-manage children who are mentally handicapped: case report.

For a small subset of mentally handicapped individuals, the medical and dental setting can be so threatening that they react violently to health care providers. Deep sedation can be administered enterally using oral ketamine, 6-8 mg/kg, combined with glycopyrrolate mixed in simple syrup and preceded by a dose of an oral benzodiazepine and sodium citrate. A case utilizing this technique to sedate an extremely combative mentally handicapped female requiring dental treatment planning in an ambulatory surgical center is described. A review of this use of ketamine and caveats concerning its use are covered.

Adolescent↗

PubMed1991

Excision of an arteriovenous malformation.

Arteriovenous malformations (AVM) are congenital vascular lesions consisting of direct communications between associated arteries and veins without an interposed capillary bed. These vessels are typically thin walled, lack an internal elastic intima, and are quite prone to hemorrhage. A previously healthy 17-year-old woman presented with severe, persistent headache. After undergoing computed tomography (CT scan) and magnetic resonance imaging (MRI), the patient was diagnosed as having an intracranial arteriovenous malformation. The anesthetic management of this patient included induction with sodium thiopental and sufentanil. General anesthesia was maintained with isoflurane in oxygen and a continuous intravenous infusion of sufentanil. Neuromuscular blockade was established prior to endotracheal intubation with vecuronium and maintained with a combination of metocurine and pancuronium. The sufentanil infusion was discontinued when vascular isolation of the AVM had been accomplished. The isoflurane was discontinued 30 minutes prior to skin closure. Neuromuscular blockade was then antagonized with neostigmine and glycopyrrolate. Spontaneous ventilation resumed when the patient's arterial carbon dioxide tension (PaCO2) was allowed to normalize. The hemodynamic character of this anesthetic course was smooth and uneventful. The patient emerged from anesthesia comfortable and lucid and experienced no perioperative anesthetic complications.

Adolescent↗

PubMed1977

Comparative antisecretory activity of several drugs in the gastric fistula squirrel monkey and rat.

A series of known antisecretory compounds, including glycopyrrolate, clonidine, propantheline bromide, CMN 131 (2-pyridylthiocetamide), and desmethylimipramine (DMI) were tested in the gastric fistula rat and monkey. The order of potency for inhibiting acid output was similar in both species. A general similarity exists in the responsiveness of the rat and monkey to gastric antisecretory agents. These data support the use of the squirrel monkey for assessment of gastric antisecretory activity.

Animals↗

PubMed1991

The effect of intraoperative retrobulbar block on anesthetic management of enucleation under general anesthesia.

This case chronicles the effect of a retrobulbar block on a coincident general anesthetic for enucleation in an elderly man. This ASA II patient had a medical history of insulin-dependent diabetes with few apparent cardiovascular complications and mild chronic obstructive pulmonary disease. Induction of anesthesia was accomplished with small doses of midazolam, droperidol, and alfentanil followed by thiamylal. The patient was intubated and maintained on isoflurane and nitrous oxide. A retrobulbar block was administered according to the surgeon's instructions without immediate, untoward consequences. Within 10 minutes the patient suffered a profound decrease in blood pressure and pulse requiring repeated doses of glycopyrrolate, phenylephrine, and ephedrine to maintain effective perfusion. These effects do not appear to have resulted from direct elicitation of the oculocardiac reflex, but rather from the loss of surgical stimuli from the block that essentially resulted in inadequate sympathetic tone. The author concludes that anesthetists in similar circumstances should anticipate the possibility of hypotension and lessened anesthetic requirements following retrobulbar block when coincident general anesthesia is planned.

Aged↗

PubMedDate not supplied

Treatment of bupivacaine-induced cardiac arrhythmias in hypoxic and hypercarbic pigs with amiodarone or bretylium.

The treatment of bupivacaine-induced cardiovascular toxicity with amiodarone or bretylium was studied using anesthetized pigs (n = 30). The pigs were given ketamine, glycopyrrolate, enflurane, and pancuronium and made hypoxic (FiO2, 12%; N2O, 88%) and hypercarbic (end-tidal CO2, 7.3-8.0%) before the administration of bupivacaine (4 mg/kg i.v.). The animals were then treated, in a randomized and double-blind fashion, with either amiodarone (n = 10) 10 mg/kg in 5% dextrose solution i.v. followed by a constant infusion of 15 mg/hour, bretylium (n = 10) 20 mg/kg in 5% dextrose solution i.v. followed by a constant infusion of 90 mg/hour, or 5% dextrose solution (n = 10). The animals were resuscitated, if required. After 30 minutes of recovery, the animals that survived were made hypoxic and hypercarbic again and given a second injection of bupivacaine (2 mg/kg IV). Bupivacaine caused marked changes in the ECG; polymorphic ventricular tachycardia (20 cases) or severe bradycardia that resulted in asystole (10 cases). Nine animals out of ten treated with amiodarone survived (stable sinus rhythm, arterial blood pressure at near control level, normocarbia), whereas six animals in the bretylium group and four in the control group died. The difference in survival between the groups was not, however, statistically significant.

Amiodarone↗

PubMed1990

Emesis and defecations induced by the 5-hydroxytryptamine (5-HT3) receptor antagonist zacopride in the ferret.

Three antiemetic compounds (zacopride, batanopride, granisetron [BRL43694]) were evaluated for the production of gastrointestinal side effects in the conscious ferret after i.v. or p.o. administration. Zacopride evoked multiple emetic and defecatory responses at clinically relevant doses (0.003-0.3 mg/kg) and in a dose-dependent manner. The oral route was the more potent one for eliciting emesis (ED50 0.033 mg/kg). At 0.3 mg/kg p.o., zacopride reliably evoked an 80 to 100% incidence of emesis and a 40 to 80% incidence of defecation. In contrast, batanopride and BRL43694 i.v. evoked a small (10%) incidence of these side effects, but only at 0.1 to 10 mg/kg doses. When given p.o. (0.00003-10 mg/kg), these latter compounds never evoked emesis and significantly reduced (P less than .05) the incidence of defecation below that of vehicle. Responses to zacopride (0.3 mg/kg p.o.) were challenged by i.p. pretreatment with the 5-hydroxytryptamine receptor agonist 2-methyl serotonin, the 5-hydroxytryptamine receptor antagonist BRL43694, the quaternary atropine derivative glycopyrrolate, the dopamine receptor antagonist domperidone or selective abdominal vagotomies. All compounds and either bilateral or dorsal vagotomy significantly reduced the incidence of emesis, but did not abolish it. Latency to first emesis was delayed by BRL43694, domperidone or dorsal vagotomy. The data suggest that the emetic response to p.o. zacopride is mediated in part by 5-hydroxytryptamine receptors residing on either enteric neurons or vagal afferents. However, the underlying pharmacology of the response may also include activation of cholinergic and dopaminergic pathways.

Administration, Oral↗

PubMed1989

Introduction to the clinical pharmacology of medetomidine.

Medetomidine is a sedative and analgesic drug intended for use in dogs and cats but it can also be successfully used in many other species. The effect of medetomidine is dose dependent at the recommended dose range (10-80 micrograms/kg for dogs and 50-150 micrograms/kg for cats). At doses higher than the recommended ones the strength of sedation does not increase, only the duration of the effect. From the cardiovascular changes induced with medetomidine, the profound bradycardia is most prominent. It can be transiently prevented with atropine or glycopyrrolate medication. An initial increase in arterial blood pressure followed by a longer lasting slightly hypotensive or normotensive period can be observed. Respiratory frequency tends to decrease but the changes stay within normal limits for resting animals. Vomiting may occur during the induction period of sedation. Occasional muscle jerks can be observed. Hypothermia has been reported in every animal sedated with medetomidine. Medetomidine can be used as preanaesthetic prior to ketamine, barbiturate and halothane anaesthesia.

Adrenergic alpha-Agonists↗

PubMed1985

Induction dose-response curves for midazolam and ketamine in premedicated ASA class III and IV patients.

Using probit analysis, dose-response curves for induction of anesthesia with midazolam or ketamine were constructed in ASA class III and IV patients premedicated with morphine, 0.1 mg/kg, and glycopyrrolate, 4 micrograms/kg. For ketamine, ED50 values for abolition of the response to verbal commands, eyelash stimulation, and painful stimulation were 0.9, 1.3, and 1.3 mg/kg, respectively; corresponding ED95 values were 1.6, 2.3, and 4.3 mg/kg, which are within the range of clinically recommended doses. For midazolam, ED50 values for verbal commands, eyelash stimulation, and painful stimulation were 0.19, 0.24, and 0.36 mg/kg, significantly greater than those previously reported for unpremedicated ASA class I and II patients. The corresponding ED95 values, 0.35, 0.43, and 1.04 mg/kg exceed previously reported values and are appreciably greater than the doses used in most previous studies of midazolam induction. Midazolam decreased systolic blood pressure slightly but significantly (from 138 +/- 4 to 128 +/- 4 mm Hg, mean +/- SEM, P less than 0.005), while diastolic blood pressure and heart rate remained unchanged. In contrast, ketamine increased systolic blood pressure (from 141 +/- 4 to 164 +/- 5 mm Hg, P less than 0.005), diastolic blood pressure (from 71 +/- 3 to 88 +/- 4 mm Hg, P less than 0.005), and heart rate (from 84 +/- 2 to 102 +/- 4 beats/min, P less than 0.005). On the basis of these data, we conclude that in ASA class III and IV patients, midazolam induction allows for hemodynamic stability and avoids the significant tachycardia and hypertension associated with equipotent doses of ketamine.

Anesthesia, Inhalation↗