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Biomedical subjects

J Kanto

Publications and source records attributed to J Kanto.

At least 19 recordsLinked to original sources

A survey of current usage of anticholinergic drugs in paediatric anaesthesia in Finland.

BACKGROUND: The aim of this survey was to obtain information about the current use of anticholinergic preanaesthetic medication in children. It was carried out as a follow-up study of the previous survey amongst Finnish anaesthesiologists in 1990. METHODS: A questionnaire was send to all members of the Finnish Society of Anaesthesiologists. Data from anaesthesiologists taking care of at least three paediatric anaesthesias/week (n= 183) were analyzed. RESULTS: In 1998 only one-third of the Finnish anaesthesiologists routinely used anticholinergics before paediatric anaesthesia. The main indications for routine anticholinergic premedication were ENT surgery (66%), eye surgery (71%) and endoscopic procedures (67%). Anticholinergic drugs were administered principally via the intravenous route (90%) briefly before induction of anaesthesia, and glycopyrrolate was the most frequently used (66%). CONCLUSION: During the last eight years in Finland the routine use of anticholinergic premedication has decreased. As in 1990 the anticholinergic prophylaxis is directed to ENT and eye surgery, endoscopic procedures and to children younger than 1 year. Use of glycopyrrolate has gained popularity at the expense of atropine and scopolamine.

Atropine

Metabolic and clinical responses to different types of premedication in children.

The metabolic and clinical responses to intravenously administered atropine+meperidine (pethidine), glycopyrrolate+meperidine, diazepam and placebo were examined in 76 healthy children. After atropine+meperidine and glycopyrrolate+meperidine administration, a significant antisialogogue effect, tachycardia and elevation in systolic blood pressure were observed. Diazepam decreased oxygen consumption (VO2) whereas atropine+meperidine increased both VO2 and energy expenditure (EE). The maximal effect of diazepam on VO2 was found 10 min after drug administration (mean difference from baseline -10.0%) and maximal effect of atropine+meperidine on VO2 and EE after 5 min (mean difference from baseline +6.0% and +3.3%, respectively). It is concluded that intravenous administration of meperidine with atropine or glycopyrrolate is followed by profound anticholinergic effects and such combinations do not appear to be suitable for clinical purposes. Although statistically significant, the alterations in VO2 and EE after diazepam and atropine+meperidine premedication can be considered clinically insignificant because they were of short duration and the measured changes represented only a fraction of fluctuation seen in normal values.

Carbon Dioxide

Spectral analysis of heart rate variability as a quantitative measure of parasympatholytic effect--integrated pharmacokinetics and pharmacodynamics of three anticholinergic drugs.

The time course and concentration-effect relationship of parasympatholytic effects of three anticholinergic drugs were investigated using spectral analysis of heart rate (HR) variability. Single intravenous (i.v.) doses of atropine (10 microg/kg), glycopyrrolate (5 microg/kg), scopolamine (5 microg/kg), and placebo were given to eight healthy volunteers in a double-blind, randomized cross-over study. Electrocardiogram (ECG) was recorded at baseline and 2.5, 5, 10, 20, and 30 minutes, and 1, 1.5, 2, 3, 4, 5, and 6 hours after drug administration, while the subjects breathed at a fixed 0.25 Hz frequency. The powers of two frequency bands (low frequency [LF] = 0.07-0.15 Hz and high frequency [HF] = 0.15-0.40 Hz) were calculated using stationary time series of R-R intervals (RRI) free from ectopic beats. To perform pharmacokinetic-pharmacodynamic (PK-PD) modeling, venous plasma drug concentrations were measured. Atropine and glycopyrrolate, and, to a lesser extent, scopolamine induced decreases in HF power and increases in LF/HF ratio of HR variability, indicating parasympatholytic activity and corresponding changes in sympathovagal balance. Maximal average decreases in HF power were 99%, 94%, and 82%, respectively, but in two scopolamine subjects, a parasympathomimetic effect was dominant. Interindividual variability was least for the Hayano index of HF power (square root (RRI HF-power)/RRI*100), and profound and consistent decreases were seen after atropine and glycopyrrolate. Pharmacokinetics were best fitted to a two-compartment open model, and effect compartment link modeling using the Hayano index was performed with the atropine and glycopyrrolate data. The best description of the PK-PD relationship for both drugs was achieved using the sigmoidal Emax model. Mean (+/-SD) EC50, sigmoidicity factor (gamma), and equilibration rate constant (k(e0)) estimates were 1.35 (+/-0.27) ng/mL, 6.07 (+/-1.98) and 11.0 (+/-5.28) l/h for atropine and 1.35 (+/-0.49) ng/mL, 4.34 (+/-1.55) and 2.26 (+/-0.81) l/h for glycopyrrolate. Spectral analysis of HR variability appears to be a powerful tool in monitoring parasympatholytic drug activity. A sigmoidal Emax model with an extremely steep concentration-response relationship was revealed for atropine and glycopyrrolate. The effects of scopolamine were more incongruous.

Adult

The effects of branched chain amino acid infusion on pain perception and plasma concentrations of monoamines.

Infusions of branched chain amino acids (BCAA) have been shown to have several CNS-mediated effects including antinociceptive action. We investigated the effects of BCAA infusion on pain perception, respiratory control, and plasma monoamine concentrations. Six healthy female volunteers were given in a double-blind, random, crossover design an 8-h infusion (1.75 ml/kg/h) of either (a) Ringers lactate, (b) conventional 4% amino acid solution, or (c) 4% BCAA solution with intervals of at least 48 h. Respiratory control was evaluated with continuous capnography. Pain perception was measured using dental dolorimetry for sharp pain, and pain transmitted by afferent C-fibers was evaluated with tourniquet test. Changes in vigilance were measured using critical flicker fusion technique. Evaluations were made for baseline, and after 2.5, 5, and 8 h. Plasma samples were collected at the same time points for amino acid and monoamine analysis. BCAA infusion resulted in significant increases of plasma concentrations of all BCAAs, with a simultaneous decrease in concentrations of aromatic amino acids. Of the measured monoamines and their metabolites dihydroxyphenylacetic acid (DOPAC) decreased, showing significant treatment effect for BCAA. Despite these changes no significant effect of BCAAs on respiratory control, vigilance, or pain perception was observed. In conclusion, despite significant changes in plasma concentrations of both amino acids and DOPAC, BCAA infusion did not show any clinically relevant antinociceptive effect.

3,4-Dihydroxyphenylacetic Acid

Pharmacokinetics and clinical effects of intramuscular scopolamine plus morphine. A comparison of two injection sites.

BACKGROUND: Intramuscular scopolamine plus morphine premedication is traditionally used when prominent sedative or antisialogogue effect is needed. Knowledge of the pharmacokinetics of scopolamine is limited due to low plasma concentrations found after therapeutic doses. This investigation compares the pharmacokinetics and the clinical responses of this drug combination injected into two commonly used injection sites. METHODS: Twelve ASA class 1 patients scheduled for minor surgery under spinal anaesthesia received scopolamine 6 micrograms/kg plus morphine 200 micrograms/kg injected in either deltoid (group D, n = 6) or gluteal (group G, n = 6) muscle. RESULTS: The peak plasma concentrations of scopolamine after deltoid or gluteal injection (2.2 vs 1.6 micrograms/l) and the time they were reached (17 vs 19 min) were comparable. The absorption of morphine was similar in both groups (Tmax 16 min), but the peak plasma concentrations were higher after deltoid injection (71 vs 49 micrograms/l). The individual variation in the elimination half-lives of both scopolamine and morphine was smaller after deltoid injection (T1/2 scopolamine 1.9 +/- 0.7 vs 2.1 +/- 1.1 h, morphine 1.3 +/- 0.7 vs 2.3 +/- 1.5 h). Moderate slowing (25%) of heart rate was found in both groups. A heavy sedation and antisialogogue effect (VAS) was found in both groups with faster occurrence of maximal effect in group D (60 vs 120-180 min). CONCLUSION: More predictable pharmacokinetics and clinical effects of intramuscular scopolamine plus morphine premedication can be achieved after an injection into deltoid muscle.

Anesthesia, Spinal

Pharmacokinetics and oral bioavailability of glycopyrrolate in children.

Based on plasma levels determined with a radioreceptor assay and following a single oral (50 micrograms/kg) and intravenous (5 micrograms/kg) administration of glycopyrrolate in six healthy children operated twice during a several weeks period, a negligible and variable oral bioavailability was found (3.3; 1.3-13.3%) (median;range). No significant changes in heart rate after oral or intravenous administration of the drug could be seen. Oral glycopyrrolate appears to have no place in paediatric premedication.

Adjuvants, Anesthesia

Cardiovascular and metabolic responses to clonidine and midazolam premedication.

In this double-blind placebo controlled study the preoperative cardiovascular and metabolic effects of intramuscular (i.m.) clonidine and midazolam are assessed. Forty-five ASA Grade I patients (n = 15 per group) undergoing plastic surgical procedures were randomly allocated to receive either placebo, clonidine 4 micrograms kg-1 or midazolam 70 micrograms kg-1. Drugs were administered into the deltoid muscle approximately 90 min prior to the scheduled induction of anaesthesia. The metabolic measurements were performed using an indirect calorimetry device. Heart rate and blood pressure were measured noninvasively. Pre-operative subjective anxiety, dryness of mouth and tiredness were assessed using visual analogue scales (VAS). Clonidine increased subjective tiredness significantly more than placebo. Clonidine also induced moderate decreases in blood pressure and heart rate. Oxygen consumption (VO2), CO2 production and energy expenditure (EE) decreased significantly after clonidine and midazolam. The decrease in VO2 and EE was maximally 11-14% on average from the base-lines after clonidine and midazolam. These effects were of longer duration after clonidine and lasted until the end of the 90 min study period. In conclusion, both clonidine and midazolam are effective as a means of decreasing pre-operative VO2 and EE.

Adrenergic alpha-Agonists

Reduction of the minimum alveolar concentration of isoflurane by dexmedetomidine.

BACKGROUND: alpha 2-Adrenergic agonists have been shown to reduce anesthetic requirements of other anesthetics, and they may even act as complete anesthetics by themselves at high doses in animal models. The present study was designed to define the interaction of intravenous infusion of dexmedetomidine, an alpha 2-adrenergic agonist, and isoflurane in patients having surgery by using the minimum alveolar concentration (MAC) of isoflurane as the measure of anesthetic potency. METHODS: Forty-nine women scheduled for abdominal hysterectomy were randomly allocated to receive either a placebo infusion (n = 16) or a two-stage infusion of dexmedetomidine with target plasma concentration of 0.3 ng/ml (n = 17) or 0.6 ng/ml (n = 16). The study drug infusion was commenced 15 min before induction of anesthesia with thiopental and alfentanil and was continued until skin incision. The end-tidal concentration of isoflurane for each patient was predetermined according to the "up-down" method of Dixon, and it was maintained for at least 15 min before the patient's response to skin incision was assessed. RESULTS: The MAC of isoflurane was 0.85% end-tidal in the control group, 0.55% end-tidal with the low dose of dexmedetomidine, and 0.45% end-tidal with the high dose of dexmedetomidine. CONCLUSIONS: The MAC of isoflurane in the control group was lower than that reported previously in similar patients having surgery, probably due to anesthesia induction with thiopental and alfentanil. Nevertheless, with the high dose of dexmedetomidine, the MAC of isoflurane was still 47% less than that without dexmedetomidine.

Adrenergic alpha-Agonists

Tropisetron and metoclopramide in the prevention of postoperative nausea and vomiting. A comparative, placebo controlled study in patients undergoing ophthalmic surgery.

One hundred and twenty patients undergoing elective ophthalmic surgery under general anaesthesia were investigated in a randomised, double-blind, parallel group study of postoperative nausea and vomiting. Patients received tropisetron 0.1 mg.kg-1, metoclopramide 0.25 mg.kg-1 or placebo given at the end of anaesthesia. In comparison with placebo, tropisetron significantly reduced the degree of nausea (p < 0.01), whereas metoclopramide reduced both nausea (p < 0.05) and vomiting (p < 0.05). There were no statistically significant differences between the two active agents in their efficacy to postoperative nausea and vomiting. The patients in the placebo group required rescue antiemesis more often in the postanaesthesia care unit. Our results suggest that tropisetron may not be suitable as a routine, primary therapy for the prevention of postoperative nausea and vomiting.

Adolescent

Pharmacological premedication for anaesthesia.

The psychological component of preoperative preparation should be completed with a selective use of drugs. The days of poly-pharmacy are over. Heavily sedated patients coming to the operation room with minimal oral secretions are not the purpose of modern premedication. Anxiolysis and slight sedation (painless patients) and analgesia (patients suffering from pain) are the main goals. Anticholinergics should be used only when needed, as is the case with premedication generally. The use of antiemetics and that of agents given for prophylaxis against allergic reactions or aspiration pneumonitis depend on specific needs of the patient. More accurate and generally accepted but simple methods are needed in studying the effects of different premedicants. The present results produced with a huge number of different more or less validated assessments can seldom be compared with each other.

Procedural Sedation

Biochemical and clinical assessment of histamine blockade.

The effects of antihistamines on biochemical stress indicators and on psychomotor and physiological functions were studied in 60 healthy patients receiving in a randomized, double-blind study either 25 mg promethazine, 150 mg ranitidine, both drugs or placebo (n = 15 in each group). Different aspects of the premedications were evaluated by determining various hormone, neurotransmitter and neurotransmitter metabolite levels in blood and cerebrospinal fluid, and subjectively using questionnaires concerning the quality of the preoperative night's sleep and visual analogue scales, and objectively by measuring changes in blood pressure and heart rate, impairment of vigilance with the Maddox wing apparatus and the critical flicker fusion threshold test. The relationships between the subjective assessments and the biochemical stress indicators were also investigated. There were no differences between the study groups in the quality of the preoperative night's sleep, estimated fear, apprehension or dizziness, or in the various physiological stress indicators. Only few statistically significant correlations were found between the subjective and biochemical assessments. It is concluded that histamine receptor antagonists used in clinical doses do not interfere with the biochemical, clinical preoperative, and physiological responses.

Adult

Maximum recommended doses of lignocaine are not toxic.

The maximum recommended doses of lignocaine are frequently exceeded in clinical practice as some blocks may need more lignocaine to produce adequate anaesthesia. We have examined the success rate of brachial plexus block, possible toxic symptoms after a dose of lignocaine 900 mg with adrenaline, and the maximum plasma concentration of lignocaine produced in 17 adult patients. In all patients, the block was excellent and no toxic symptoms were encountered. The highest mean lignocaine plasma concentration was 2.9 micrograms ml-1 45 min after the block. We conclude that in brachial plexus block, the dose of lignocaine with adrenaline can be as high as 900 mg without fear of toxic symptoms.

Adolescent

The metabolic effects of oral tizanidine in healthy volunteers.

This pilot study compared the metabolic effects of placebo and 6 mg and 12 mg of oral tizanidine in random double-blind cross-over fashion in five healthy volunteers. The metabolic measurements were made with a portable metabolic chart (Deltatrac, Datex/Instrumentarium, Helsinki, Finland). Heart rate (HR), systolic (BPS), mean (BPM) and diastolic (BPD) blood pressure were measured noninvasively. Subjective assessment of tiredness and dryness of mouth were measured by using visual analogue scales (VAS). There were no statistically significant differences in tiredness or dryness of mouth between the groups. BPD decreased significantly after both doses of tizanidine when compared to placebo (by an average of 12% after 6 mg of tizanidine and 15% after 12 mg of tizanidine from the baseline). Oxygen consumption and energy expenditure decreased significantly after 6 and 12 mg of tizanidine when compared to placebo. The average decrease in oxygen consumption was 3% after 6 mg of tizanidine and 8% after 12 mg of tizanidine, when compared to the baseline. Energy expenditure decreased by an average of 5% after 6 mg of tizanidine and 9% after 12 mg of tizanidine, when compared to the baseline. There were no other statistically significant differences between the groups. This study indicates that 6 and 12 mg of oral tizanidine can be useful for reducing energy expenditure and oxygen consumption without prominent cardiovascular effects.

Administration, Oral

Dexmedetomidine as intramuscular premedication for day-case cataract surgery. A comparative study of dexmedetomidine, midazolam and placebo.

The effects of dexmedetomidine 1.0 microgram.kg-1, midazolam 20 micrograms.kg-1 and saline placebo were assessed in a double-blind, randomised study in 90 patients undergoing day-case cataract surgery under regional anaesthesia. The trial drug was injected into the deltoid muscle 45 min before the peri-ocular block. Dexmedetomidine 1.0 microgram.kg-1 decreased intra-ocular pressure before, during and after surgery. The maximum reduction in mean (SD) intra-ocular pressure occurred in the dexmedetomine group just before discharge from hospital (17.7 (2.8) mmHg to 11.5 (2.9) mmHg) (p < 0.001 compared with midazolam and placebo). In contrast, midazolam did not differ from saline placebo. Dexmedetomidine and midazolam produced a similar sedative effect of short duration. Dexmedetomidine induced a moderate decrease in blood pressure (p < 0.001 compared with placebo) and a slight but statistically significant decrease in heart rate throughout the study period (p < 0.001 compared with placebo). Dexmedetomidine 1.0 microgram.kg-1 intramuscularly, effectively reduced intra-ocular pressure and produced short-acting sedation with marginal cardiovascular effects; it may be a useful premedicant drug for elderly patients undergoing day-case cataract surgery under regional anaesthesia.

Adrenergic alpha-Agonists

The effects of regional anaesthesia for caesarean section on maternal and fetal blood flow velocities measured by Doppler ultrasound.

We studied the effects of spinal anaesthesia (Group S), epidural anaesthesia (Group E), and combined spinal and epidural anaesthesia (Group SE), on maternal and fetal blood flow in 24 healthy parturients (n = 8/group) with uncomplicated singleton pregnancies using Doppler technique. Prior to the induction of anaesthesia, the patients were prehydrated with balanced electrolyte solution 15 ml.kg-1 over a period of 15 min. After the induction of regional anaesthesia, the systolic blood pressure was maintained within 15% limits of the preoperative values using prophylactic etilefrine infusion in Groups S and SE. The flow velocity waveforms of the maternal femoral artery, the main branch of the uterine artery (placental side), the foetal umbilical and middle cerebral arteries were recorded by Doppler technique before and after prehydration as well as after onset of T7 analgesia and the pulsatility indices (PI) were derived. Rapid intravenous prehydration had no effects on uteroplacental or fetal circulation as indicated by unaltered uterine, umbilical, and fetal middle cerebral artery PIs. After the onset of T7 analgesia, the uterine artery PI was increased in Group S indicating increased uterine vascular resistance while no changes occurred in Groups E and SE. No adverse effects were observed on the neonates as indicated by the Apgar score and the umbilical artery and vein acid-base status in any of the groups.

Adult