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Biomedical subjects

R Aantaa

Publications and source records attributed to R Aantaa.

33 records · Page 2Linked to original sources
PubMed1997

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↗
PubMed1995

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↗
PubMed1995

Molecular pharmacology of alpha 2-adrenoceptor subtypes.

alpha 2-adrenergic receptors mediate many of the physiological actions of the endogenous catecholamines adrenaline and noradrenaline, and are targets of several therapeutic agents. alpha 2-adrenoceptor agonists are currently used as antihypertensives and as veterinary sedative anaesthetics. They are also used in humans as adjuncts to anaesthesia, as spinal analgesics, and to treat opioid, nicotine and alcohol dependence and withdrawal. Three human alpha 2-adrenoceptor subtype genes have been cloned and designated alpha 2-C10, alpha 2-C4, and alpha 2-C2, according to their location on human chromosomes 10, 4 and 2. They correspond to the previously identified pharmacological receptor subtypes alpha 2A, alpha 2C and alpha 2B. The receptor proteins share only about 50% identity in their amino acid sequence, but some structurally and functionally important domains are very well conserved. The most obvious functionally important differences between the receptor subtypes are based on their different tissue distributions; e.g. the alpha 2A subtype appears to be an important modulator of noradrenergic neurotransmission in the brain. The three receptors bind most alpha 2-adrenergic drugs with similar affinities, but some compounds (e.g. oxymetazoline) are capable of discriminating between the subtypes. Clinically useful subtype selectivity cannot be achieved with currently available pharmaceutical agents. The second messenger pathways of the three receptors show many similarities, but small functional differences between the subtypes may turn out to have important pharmacological and clinical consequences. All alpha 2-adrenoceptors couple to the pertussis-toxin sensitive inhibitory G proteins Gi and G(o), but recent evidence indicates that also other G proteins may interact with alpha 2-adrenoceptors, including Gs and Gq/11. Inhibition of adenylyl cyclase activity, which results in decreased formation of cAMP, is an important consequence of alpha 2-adrenoceptor activation. Many of the physiological effects of alpha 2-adrenoceptor activation cannot, however, be explained by decreases in cAMP formation. Therefore, alternative mechanisms have been sought to account for the various effects of alpha 2-adrenoceptor activation on electrophysiologic, secretory and contractile cellular responses. Recent results obtained from studies on ion channel regulation point to the importance of calcium and potassium channels in the molecular pharmacology of alpha 2-adrenoceptors.

Adenylyl Cyclase Inhibitors↗
PubMed1994

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↗
PubMed1994

Comparison of intramuscular dexmedetomidine and midazolam premedication for elective abdominal hysterectomy.

The purpose of this study was to compare the perioperative effects of the intramuscular (i.m.) alpha 2 agonist, dexmedetomidine (DEX), and midazolam (MID) premedication. The study comprised 192 women (64 per group) scheduled for abdominal hysterectomy. The doses of the study drugs were chosen to obtain equal sedative effects. The three groups were: 1) i.m. DEX (2.5 micrograms/kg) and intravenous (i.v.) placebo (DexPla group), 2) i.m. DEX and i.v. fentanyl (FENT) (1.5 micrograms/kg) (DexFent group), and 3) i.m. MID (0.08 mg/kg) and i.v. FENT (MidFent group). I.m. drugs were administered 45-90 min before induction of anesthesia. Preoperative sedation and anxiolysis after DEX was comparable to that after MID. The maximum arterial blood pressure response to endotracheal intubation was blunted in the DexFent group, while in the two other groups blood pressure increased 30-34 mm Hg after endotracheal intubation. The mean isoflurane concentration during surgery was 0.14% in the DexFent group, 0.24% in the DexPla group, and 0.34% in the MidFent group (P < 0.001). During surgery, bradycardia (heart rate < 40 bpm) was observed in 6.2% of DEX patients, and no MID patients, whereas postoperatively 14.1% of DEX patients and 1.6% of MID patients had bradycardia. Fewer patients suffered from postoperative shivering after DEX (10%) than after MID (52%). We conclude that DEX has many desirable effects, but side effects such as bradycardia may limit its routine use in ASA physical status I-II patients.

Adult↗
PubMed1994

Metabolic and subjective responses to oral diazepam and midazolam.

Diazepam premedication decreases the overall metabolic rate and oxygen consumption. Whether its properties are shared by midazolam is not known. In this study, eight healthy male volunteers were given oral diazepam (10 mg), midazolam (15 mg) and placebo in a random double-blind cross-over fashion. Metabolic responses were measured using an indirect calorimetry device. Subjective responses were measured using a visual analogue scale. Plasma concentrations of diazepam, midazolam and desmethyldiazepam were analysed and correlated to changes in metabolic and subjective responses. When compared to placebo, both diazepam and midazolam significantly decreased oxygen consumption (P < 0.01 in pairwise comparisons) and energy expenditure (P < 0.01 in pairwise comparisons). While there was a significant correlation between the plasma concentrations of diazepam and the changes in metabolic parameters, no such correlation was found with midazolam. Both diazepam and midazolam were subjectively more sedative than placebo (P < 0.05). There was no significant difference between the sedative effects of diazepam and midazolam, but diazepam was subjectively better tolerated than midazolam. These results indicate that both diazepam and midazolam, in addition to their CNS effects, significantly decrease the overall metabolic rate and oxygen consumption in healthy volunteers.

Administration, Oral↗
PubMed1991

A comparison of dexmedetomidine, and alpha 2-adrenoceptor agonist, and midazolam as i.m. premedication for minor gynaecological surgery.

The effects of i.m. dexmedetomidine 1.0 micrograms kg-1, a new alpha 2-adrenoceptor agonist, were compared with those of i.m. midazolam 0.08 mg kg-1 and placebo on vigilance, anaesthetic requirements, haemodynamic state and plasma catecholamine concentrations in a double-blind placebo-controlled study in 107 healthy (ASA physical status I-II) women undergoing cervical dilatation and uterine curettage. The premedicants were administered i.m. 60 min before induction of anaesthesia with thiopentone. Nitrous oxide 70% in oxygen and thiopentone were used for maintenance. Both premedicants were tolerated well and no serious haemodynamic or other adverse events occurred. Dexmedetomidine caused moderate reductions in arterial pressure (maximally by 20%) and heart rate (maximally by 15%). Atropine was administered to two dexmedetomidine-premedicated patients because of bradycardia less than 45 beat min-1. Both premedicants decreased the plasma concentrations of noradrenaline by about 50%, but only dexmedetomidine attenuated the catecholamine response to anaesthesia and surgery. The thiopentone requirements were decreased significantly (P = 0.003) by both dexmedetomidine (17%) and midazolam (19%). Recovery times were 11.3 (SD 4.2) min after midazolam, 8.5 (5.2) min after dexmedetomidine and 5.6 (11.4) min after placebo (P = 0.006 between midazolam and placebo groups, other differences ns).

Adrenergic alpha-Agonists↗
PubMed1991

Intramuscular dexmedetomidine, a novel alpha 2-adrenoceptor agonist, as premedication for minor gynaecological surgery.

The effects of three different doses (0.5, 1.0 and 1.5 micrograms/kg) of dexmedetomidine, a novel alpha 2-adrenoceptor agonist, on vigilance, anaesthetic requirements, haemodynamics, and plasma catecholamine levels were investigated in a double-blind placebo-controlled study in 20 healthy (ASA physical status I-II) women scheduled for uterine dilatation and curettage (UD&C). The drug was administered intramuscularly 60 min before induction of anaesthesia with thiopentone, N2O/O2 (70/30%) and thiopentone was used for maintenance. There were no significant differences between the groups in thiopentone requirements, plasma adrenaline concentrations, or subjective or objective assessment of sedation before anaesthesia and UD&C. Blood pressure, heart rate, and plasma noradrenaline levels were reduced after dexmedetomidine, with three patients receiving atropine for excessive bradycardia (less than 45 beats min-1). The haemodynamic as well as the sedative effects of dexmedetomidine after surgery lasted until the end of the observation period, 4 h after the injection of the drug, indicating that intramuscular administration of this premedication agent may result in a longer than optimal duration of pharmacological actions in connection with short surgical procedures.

Adrenergic alpha-Agonists↗
PubMed1991

Assessment of the sedative effects of dexmedetomidine, an alpha 2-adrenoceptor agonist, with analysis of saccadic eye movements.

Single intravenous doses (0.5 microgram/kg and 1.0 microgram kg) of dexmedetomidine (4(5)-(1-(2,3-dimethylphenyl)ethyl)imidazole), a selective alpha 2-adrenoceptor agonist, and saline placebo were administered to six healthy volunteers (4 males and 2 females) in a double-blind, placebo-controlled cross-over study. The effects on vigilance were assessed using both subjective estimation (visual analogue scale, VAS) and objective tests (critical flicker fusion frequency, CFF; the Maddox wing; saccadic eye movement analysis). Dose-dependent subjective sedation was seen in VAS measurements, and impairment of vigilance was observed in CFF, Maddox wing and peak saccadic velocity, while saccade latency was not influenced by dexmedetomidine. The changes in vigilance were concurrent with moderate reductions in blood pressure and heart rate. CFF, the Maddox wing and peak saccadic velocity all proved sensitive in the assessment of sedation induced by dexmedetomidine.

Adrenergic alpha-Agonists↗
PubMed1990

Difference in action between oral triazolam and zopiclone.

The effects of oral triazolam 0.25 mg and zopiclone 7.5 mg in 7 supine volunteers were compared by means of quantitative measurements of the EEG, saccadic eye movements, visual analogue scale (VAS) for alertness, critical flicker fusion frequency (CFF) and the Maddox wing. Zopiclone reached its maximum effect earlier (62 min) than triazolam (91 min; CFF). On linear regression analysis the average rate constant (regression coefficient) of onset of action of zopiclone was significantly greater than that of triazolam (0.29 vs. 0.17). Triazolam and zopiclone had similar effects, but zopiclone seemed to have a faster onset of action, probably indicating swifter absorption in supine subjects. Quantitative EEG evaluation gave parallel results to the other parameters used, but triazolam and zopiclone showed a dissimilar mechanism of action, as characterized by changes in the alpha frequency.

Administration, Oral↗
PubMed1990

Dexmedetomidine, an alpha 2-adrenoceptor agonist, reduces anesthetic requirements for patients undergoing minor gynecologic surgery.

The effects of dexmedetomidine, an alpha 2-adrenoceptor agonist, on vigilance, thiopental anesthetic requirements, and the hemodynamic, catecholamine, and hormonal responses to surgery were investigated in healthy (ASA physical status 1) women scheduled for dilatation and curettage (D & C) of the uterus. Fifteen minutes before induction they received single iv doses of either dexmedetomidine (0.5 micrograms/kg; n = 19) or saline (n = 20) in a double-blind fashion. Anesthesia was induced with thiopental and maintained with N2O/O2 (70/30%) and thiopental. Dexmedetomidine was well tolerated and no serious drug-related subjective side-effects or adverse events were observed. The most prominent subjective effects were fatigue and decreased salivation. The total amount of thiopental needed to perform D & C of the uterus was reduced approximately 30% (from 456 +/- 141 mg [mean +/- SD] after saline to 316 +/- 79 mg after dexmedetomidine). This was mostly due to a smaller induction dose in the group receiving dexmedetomidine. Dexmedetomidine appeared to improve the recovery from anesthesia as measured by visual analogue scales (VAS) on fatigue and nausea. The plasma concentration of norepinephrine was decreased by 56% after dexmedetomidine implying decreased sympathetic nervous activity. Systolic and diastolic blood pressure were moderately reduced after dexmedetomidine administration. The authors conclude that dexmedetomidine preanesthetic medication decreases thiopental anesthetic requirements and improves the recuperation from anesthesia with no serious hemodynamic or other adverse effects. Further studies in patients undergoing more stressful surgery are indicated.

Adrenergic alpha-Agonists↗
PubMedDate not supplied

Transarterial brachial plexus anesthesia for hand surgery: a retrospective analysis of 346 cases.

STUDY OBJECTIVES: To study the safety and efficacy of the transarterial approach to brachial plexus block with 60 to 70 ml of local anesthetic solution, and to compare the success and complication rates of this block performed by experienced or inexperienced anesthesiologists. DESIGN: Retrospective analysis of 346 records of ASA physical status I-IV patients who underwent elective unilateral orthopedic upper limb surgery with transarterial plexus anesthesia. SETTING: University teaching hospital. MEASUREMENTS AND MAIN RESULTS: Blood pressure (BP) and heart rate were measured at 5-minute intervals. Analgesia was registered as successful, incomplete, or failed. Any patient complaints or adverse reactions were recorded. The first 60 ml of local anesthetic provided surgical analgesia to 64% of patients. With a supplemental 10 ml of anesthetic, the overall success rate was 94%, with only 19 of 346 patients requiring general anesthesia. Experience in performing the block increased the success rate from 90% to 98% (p < 0.001). Six patients experienced either nausea or a transient BP decrease that did not require medication. There was no record of toxic or other serious adverse reaction. CONCLUSIONS: Transarterial brachial plexus block administered with a 60 to 70 ml dose of local anesthetic provides surgical analgesia for hand surgery with an excellent success rate and without serious adverse effects.

Adolescent↗