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H Scheinin

Publications and source records attributed to H Scheinin.

At least 37 records · Page 2Linked to original sources

Correlation properties and complexity of perioperative RR-interval dynamics in coronary artery bypass surgery patients.

BACKGROUND: Dynamic measures of heart rate variability (HRV) may uncover abnormalities that are not easily detectable with traditional time and frequency domain measures. The purpose of this study was to characterize changes in RR-interval dynamics in the immediate postoperative phase of coronary artery bypass graft (CABG) surgery using traditional and selected newer dynamic measures of HRV. METHODS: Continuous 24-h electrocardiograph recordings were performed in 40 elective CABG surgery patients up to 72 h postoperatively. In one half of the patients, Holter recordings were initiated 12-40 h before the surgery. Time and frequency domain measures of HRV were assessed. The dynamic measures included a quantitative and visual analysis of Poincaré plots, measurement of short- and intermediate-term fractal-like scaling exponents (alpha1 and alpha2), the slope (beta) of the power-law regression line of RR-interval dynamics, and approximate entropy. RESULTS: The SD of RR intervals (P < 0.001) and the ultra-low-, very-low-, low-, and high-frequency power (P < 0.01, P < 0.001, P < 0.001, P < 0.01, respectively) measures in the first postoperative 24 h decreased from the preoperative values. Analysis of Poincaré plots revealed increased randomness in beat-to-beat heart rate behavior demonstrated by an increase in the ratio between short-term and long-term HRV (P < 0.001) after CABG. Average scaling exponent alpha1 of the 3 postoperative days decreased significantly after CABG (from 1.22 +/- 0.15 to 0.85 +/- 0.20, P < 0.001), indicating increased randomness of short-term heart rate dynamics (i.e., loss of fractal-like heart rate dynamics). Reduced scaling exponent alpha1 of the first postoperative 24 h was the best HRV measure in differentiating between the patients that had normal (</= 48 h, n = 33) or prolonged (> 48 h, n = 7) intensive care unit stay (0.85 +/- 0.17 vs. 0.68 +/- 0.18; P < 0.05). In stepwise multivariate logistic regression analysis including typical clinical predictors, alpha1 was the most significant independent predictor (P < 0.05) of long intensive care unit stay. None of the preoperative HRV measures were able to predict prolonged intensive care unit stays. CONCLUSIONS: In the selected group of patients studied, a decrease in overall HRV was associated with altered nonlinear heart rate dynamics after CABG surgery. Current results suggest that a more random short-term heart rate behavior may be associated with a complicated clinical course. Analysis of fractal-like dynamics of heart rate may provide new perspectives in detecting abnormal cardiovascular function after CABG.

Aged↗

Acute inhibition of oestrogen biosynthesis does not affect serum leptin levels in young men.

OBJECTIVE: Leptin plays an important role in the regulation of reproduction. To explore the contribution of oestradiol to serum leptin levels in men, we measured the concentrations of serum leptin and insulin after inhibition of oestrogen biosynthesis by selective blockade of the aromatase enzyme. DESIGN: The study had a double-blind parallel group design. METHODS: The aromatase inhibitor, MPV 2213ad, was given to eight healthy male volunteers as a single dose of 100mg. Eight men received placebo. Serum leptin and insulin were determined from blood samples collected at 0800h, 1600h and 2000h both on the actual test day (day 0) and on the previous day (day -1), and from single blood samples taken in the morning of days 1, 2, 4 and 7. Changes in serum leptin were correlated with those seen in serum oestradiol, testosterone, LH, FSH, cortisol and aldosterone, which were determined earlier. RESULTS: After the aromatase inhibitor administration, mean serum oestradiol concentration was reduced by 74% from the baseline compared with a 19% reduction in the placebo group (P for difference <0.001), and returned to pre-treatment levels within four days. Despite marked changes in serum oestradiol and sustained elevations in serum testosterone, LH and FSH concentrations, serum leptin concentrations were similar in the group receiving the aromatase inhibitor and in the placebo group. We found a weak correlation between serum oestradiol and leptin, which could not be reproduced when the percentage changes in these variables were analysed. CONCLUSION: Marked short-term reduction in serum oestradiol concentration has no effect on serum leptin levels in young men.

Adult↗

A double-blind study of MPV-2213ad, a novel aromatase inhibitor, in healthy male subjects.

OBJECTIVE: Novel aromatase inhibitors are developed with requirements of high potency and selectivity for the aromatase enzyme. The hormonal effects of a new, non-steroidal competitive inhibitor of the aromatase enzyme, MPV-2213ad, were investigated in this study. METHODS: The study was conducted as a double-blind, placebo controlled phase I study, where 32 healthy male volunteers were randomized to receive a single oral dose of either 0.3, 3 or 100 mg of MPV-2213ad or placebo. Serum concentrations of estradiol (E2), testosterone, follicle stimulating hormone (FSH), luteinizing hormone (LH), cortisol and aldosterone were determined from samples taken 0, 4, 8 h and 12 h during the day of drug administration and 1, 2, 4 and 7 days after drug intake. The individual diurnal variation of circulating hormone concentrations was determined in all participants at 0, 4, 8 h and 12 h on the day before drug intake. Specimens for hematological and biochemical analyses were also collected. RESULTS: A dose-dependent and statistically significant (P < 0.001) decrease in serum E2 concentrations was induced by MPV-2213ad. Lowest mean values were observed 8-12 h after drug administration and at 24 h the reductions were 10%, 34% and 69% from baseline in the 0.3-mg, 3-mg and 100-mg groups, compared with an 18% increase in the placebo group. Serum E2 concentrations returned to baseline within 4 days in all study subjects. A significant increase was observed in the serum concentrations of testosterone (P = 0.016), LH (P = 0.002) and FSH (P < 0.001) after administration of MPV-2213ad. Serum concentrations of cortisol and aldosterone were unaffected by MPV-2213ad. The drug was well tolerated. CONCLUSION: Single oral doses of MPV-2213ad, given to healthy male subjects, induced hormonal effects typical for a specific and selective inhibitor of the aromatase enzyme. Importantly, this study design with the determination of the diurnal rhythm in the levels of the corresponding hormones gives additional validity on the results.

Adult↗

Ketamine antagonises alfentanil-induced hypoventilation in healthy male volunteers.

BACKGROUND: The effects of ketamine on respiration, alone, or in combination with opioids, have not been completely clarified. Both stimulant and depressant effects have been reported, as well as attenuation of opioid-induced hypoventilation at the expense of increased oxygen consumption. These conflicting results might partly be due to dose-dependent mechanisms. We have, therefore, determined the ventilatory effects of ketamine, in combination with alfentanil, using infusions to different pseudo steady-state concentrations. METHODS: On two separate days, eight healthy male volunteers were given alfentanil as a continuous computer-controlled infusion, aiming at a plasma concentration of 50 ng x mL(-1). After reaching apparent steady-state for alfentanil, racemic ketamine or placebo was administered in a protocol randomised for the two days. On the ketamine days a computer-controlled infusion, aiming for escalating ketamine plasma concentrations of 50, 100 and 200 ng x mL(-1), was added to the alfentanil infusion. On the placebo days saline was added. Using a face-mask with an occlusion valve, respiratory parameters were measured during air-breathing and after 6 repetitive 30-s CO2 challenges. RESULTS: The alfentanil infusion induced hypoventilation by decreasing respiratory rate, while tidal volume and respiratory drive were unaffected. This hypoventilation was antagonised by ketamine in a concentration-dependent manner mainly through an increase in respiratory rate. The CO2 response was not affected by alfentanil or ketamine. CONCLUSION: In the dose range of interest for postoperative, intensive-care and pain-clinic settings, ketamine antagonises the resting hypoventilation induced by alfentanil.

Adult↗

Heart rate variability in healthy volunteers during normobaric and hyperbaric hyperoxia.

Inhaled supranormal partial pressure of oxygen induces bradycardia and peripheral vasoconstriction. The exact mechanism of the decreasing heart rate is not clear, but the autonomic nervous system is partly involved. In the present study the role of the autonomic nervous system in hyperoxic bradycardia was evaluated by using the power spectral analysis of heart rate variability. Ten healthy volunteers participated in four experiments: (i) hyperbaric oxygen treatment (100% oxygen at 2.5 ATA), (ii) hyperbaric air treatment (O2 21% at 2.5 ATA), (iii) oxygen treatment at normal pressure (100% O2, 1 ATA) and (iv) air breathing at normal pressure (21% O2, 1 ATA). During the experiments, ECG was registered and subjected to power spectral analysis. The volunteers rated their perception of temperature, ear discomfort, sweating and excitement on a visual analogue scale. Statistical comparison of the results of the four trials was conducted with a two-way ANOVA for repeated measurements. Heart rate decreased during all interventions, but there were no statistically significant differences between the sessions. High frequency variability of heart rate variability and Hayano's index of HF power increased and LF/HF ratio decreased with increasing partial pressure of oxygen. Our results suggest, that normobaric and hyperbaric hyperoxia increase parasympathetic influence in the regulation of the heart.

Adult↗

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↗

Effect of hyperbaric conditions on plasma stress hormone levels and endothelin-1.

To study a generalized stress reaction as well as endothelin-1 concentrations during moderate hyperbaria and hyperbaric oxygen (HBO2), eight professional divers were exposed to air (O2 21%, AIR) and oxygen (O2 100%, HBO2) at 2.5 atm abs for 60 min in separate sessions. Plasma concentrations of epinephrine, norepinephrine, dihydroxyphenylglycol (metabolite of norepinephrine), cortisol, ADH, renin, aldosterone, pro-ANP, and endothelin-1 were analyzed before, during, and 20 min after the treatments. Endothelin-1 increased significantly (6% during HBO2 and 18% during AIR, and 30 and 34% after the treatments, respectively, P = 0.032). There was no statistically significant difference in the changes of mean norepinephrine and dihydroxyphenylglycol levels between the treatments, although both seemed to change slightly during the treatments, but not over the baseline (time effect P = 0.031 and P = 0.011, respectively). Cortisol levels decreased significantly (P = 0.001) during the treatments. No significant changes were found in other analyzed hormones. The authors concluded that a) HBO2, and hyperbaric air at 2.5 atm abs do not induce a generalized hormonal stress reaction, and b) endothelin-1 increases during HBO2 and hyperbaric air at 2.5 atm abs.

Aldosterone↗

CYP2D6 polymorphism is not crucial for the disposition of selegiline.

OBJECTIVE: To determine the possible impact of CYP2D6 polymorphism on the pharmacokinetics and pharmacodynamics of selegiline. METHODS: Five poor metabolizers and 8 extensive metabolizers of debrisoquin (INN, debrisoquine) were given 10 mg selegiline hydrochloride. The concentrations of selegiline and its main metabolites in serum were determined for 4 days. The pharmacodynamics were quantitated by measuring platelet monoamine oxidase type B activity for 3 weeks. In addition, the effect of selegiline and its main metabolites on the CYP2D6-catalyzed dextromethorphan O-demethylase activity and the effect of quinidine on the metabolism of selegiline were studied in human liver microsomes. RESULTS: Peak serum concentrations of selegiline were reached rapidly and ranged from 1 to 32 nmol/L. The metabolite concentrations were considerably higher and remained so for a longer period. There were no significant differences in the pharmacokinetic parameters of selegiline, desmethylselegiline, and l-amphetamine between poor metabolizers and extensive metabolizers. However, the area under the serum concentration-time curve (AUC) values of l-methamphetamine were, on average, 46% higher (P = .01) in poor metabolizers than in extensive metabolizers. No significant correlations were found between debrisoquin metabolic ratio and AUC values of selegiline or its metabolites, except for l-methamphetamine (rs = 0.90; P < .001). The maximum monoamine oxidase type B inhibition was 97% in both groups. The inhibitory potency of selegiline, desmethylselegiline, and l-methamphetamine toward dextromethorphan O-demethylase was very low (50% inhibitory concentration values from 160 to 580 mumol/L). Quinidine (< or = 100 mumol/L) did not inhibit the formation of desmethylselegiline or l-methamphetamine from selegiline. CONCLUSIONS: CYP2D6 is not important in the primary elimination of selegiline, and the biological effect of selegiline seems to be similar in poor metabolizers and extensive metabolizers of debrisoquin. The inhibitory effect of selegiline and its main metabolites on CYP2D6 activity seems to be negligible.

Adrenergic Agents↗

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↗

Nocturnal body movements and hypoxemia in middle-aged females after lower abdominal surgery under general anesthesia: a study with the static-charge-sensitive bed (SCSB).

OBJECTIVE: The aim of this study was to evaluate the feasibility of the static-charge-sensitive-bed (SCSB) combined with pulse oximetry (SpO2) for postoperative monitoring and to determine variables which could be used for evaluating the quality of postoperative sleep and breathing. METHODS: The frequency of body movements and the perioperative breathing abnormalities were assessed using the SCSB and pulse oximeter in 15 female ASA-class I-II patients undergoing elective lower abdominal surgery under general anesthesia. Anesthesia and control of postoperative pain followed standard practice. The patients were monitored during one preoperative and three consecutive postoperative nights. Movements were analyzed according to their duration and time interval. The effect of opioids was evaluated by measuring arterial oxyhemoglobin saturation (SpO2) with pulse oximetry for one hour before and two hours after administration of standard doses of oxycodone. RESULTS: The total movement time per hour increased during the first postoperative night (p = 0.003). Conversely, periodic movement activity decreased significantly during the three postoperative nights (p = 0.05, p < 0.001, p = 0.007). The mean SpO2 decreased during the first postoperative night (95.5% vs. 94.2%, p = 0.002), but returned to the preoperative level during the following nights. No episodes of apnea with significant oxygen desaturation (a decrease in SpO2 > 5%) were observed. Opioid administration was associated with decreased mean SpO2 (94.8% vs. 93.6%, p = 0.02), but did not lead to clinically significant hypoxemia (lowest observed SpO2 89.8%). CONCLUSIONS: Postoperative periodic movement activity was suppressed, but sleep remained fragmented with frequent body movements. In our middle-aged non-obese females (ASA I-II), no severe postoperative hypoxemia was observed during the three-nights postoperative survey. Perioperative movement monitoring with the SCSB was a valuable tool in rejecting movement artefacts of SpO2 and in evaluating general sleep quality.

Abdomen↗

Hormonal effects of MPV-2213ad, a new selective aromatase inhibitor, in healthy male subjects. A phase I study.

AIMS: A novel non-steroidal competitive inhibitor of the aromatase enzyme, MPV-2213ad, was entered into an open dose-escalation study. The objective of this study was to investigate the tolerability and efficiency of this new compound with assessment of the hormonal effects after study drug administration. METHODS: MPV-2213ad was given to 39 healthy male volunteers. Single increasing oral doses of 0.003, 0.03, 0.3, 3, 9, 30 and 100 mg were given to three subjects at each dose level, after which ten subjects received the 300 mg dose and eight subjects the highest 600 mg dose of MPV-2213ad. RESULTS: Serum oestradiol levels were suppressed by 58-65% when MPV-2213ad was given at doses between 0.3 and 30 mg. A reduction in serum oestradiol levels by 83% from baseline was achieved with the 300 mg dose. No additional decrease was seen with the highest dose. The suppression lasted longer with higher doses of MPV-2213ad. After the 300 and 600 mg doses serum oestradiol returned to baseline within 4 days. Marked increases in serum concentrations of testosterone, androstenedione, 17-OH-progesterone, LH and FSH were also observed at doses between 100 and 600 mg of MPV-2213ad. The drug was well-tolerated and the adverse events were mild or moderate including hot flushes, mild vertigo, nausea, acne and gastrointestinal discomfort. CONCLUSIONS: MPV-2213ad has a potent, dose-dependent inhibitory effect on serum oestradiol. It was selective for the aromatase enzyme with no signs of adreno-cortical suppression or haematological or biochemical toxicity.

Adult↗

The influence of drug input rate on the development of tolerance to frusemide.

AIMS: Understanding the impact of drug input rate on its pharmacokinetic-pharmacodynamic relationship may lead to a more optimal drug therapy. The aim of the present study was to investigate the influence of the rate of administration on tolerance development to frusemide, by giving the drug at four different infusion rates. METHODS: Eight healthy volunteers were given 10 mg of frusemide on four different occasions, as a constant-rate intravenous infusion during 10, 30, 100 and 300 min, respectively. Urinary volume and contents of frusemide and sodium were measured in samples collected over 8 h. RESULTS: The four different infusion rates systematically influenced the frusemide excretion rate versus diuretic and natriuretic response relationship. Counter-clockwise hysteresis occurred for the most rapid infusion rate, whereas a progressive clockwise hysteresis was observed for the slower infusions, indicating development of tolerance. For each subject, diuresis and natriuresis were modeled for all four treatments simultaneously, using a feedback tolerance model. It was not possible to describe the data using a model without tolerance. The time course of tolerance development showed remarkable differences between the infusion rates. The intensity of maximum tolerance development was significantly less for the slowest infusion rate compared with the more rapid infusions and it appeared significantly later. However, no differences in diuretic or natriuretic response were found between the treatments. CONCLUSIONS: The direction of the hysteresis loop is dependent on the input rate of frusemide. After the administration of a single low dose of frusemide, the time course of tolerance, rather than the integrated time course of tolerance, is influenced by the drug input rate.

Adult↗

Reversal of the sedative and sympatholytic effects of dexmedetomidine with a specific alpha2-adrenoceptor antagonist atipamezole: a pharmacodynamic and kinetic study in healthy volunteers.

BACKGROUND: Specific and selective alpha2-adrenergic drugs are widely exploited in veterinary anesthesiology. Because alpha2-agonists are also being introduced to human practice, the authors studied reversal of a clinically relevant dexmedetomidine dose with atipamezole, an alpha2-antagonist, in healthy persons. METHODS: The study consisted of two parts. In an open dose-finding study (part 1), the intravenous dose of atipamezole to reverse the sedative effects of 2.5 microg/kg of dexmedetomidine given intramuscularly was determined (n = 6). Part 2 was a placebo-controlled, double-blinded, randomized cross-over study in which three doses of atipamezole (15, 50, and 150 microg/kg given intravenously in 2 min) or saline were administered 1 h after dexmedetomidine at 1-week intervals (n = 8). Subjective vigilance and anxiety, psychomotor performance, hemodynamics, and saliva secretion were determined, and plasma catecholamines and serum drug concentrations were measured for 7 h. RESULTS: The mean +/- SD atipamezole dose needed in part 1 was 104+/-44 microg/kg. In part 2, dexmedetomidine induced clear impairments of vigilance and psychomotor performance that were dose dependently reversed by atipamezole (P < 0.001). Complete resolution of sedation was evident after the highest (150 microg/kg) dose, and the degree of vigilance remained high for 7 h. Atipamezole dose dependently reversed the reductions in blood pressure (P < 0.001) and heart rate (P = 0.009). Changes in saliva secretion and plasma catecholamines were similarly biphasic (i.e., they decreased after dexmedetomidine followed by dose-dependent restoration after atipamezole). Plasma norepinephrine levels were, however, increased considerably after the 150 microg/kg dose of atipamezole. The pharmacokinetics of atipamezole were linear, and elimination half-lives for both drugs were approximately 2 h. Atipamezole did not affect the disposition of dexmedetomidine. One person had symptomatic sinus arrest, and another had transient bradycardia approximately 3 h after receiving dexmedetomidine. CONCLUSIONS: The sedative and sympatholytic effects of intramuscular dexmedetomidine were dose dependently antagonized by intravenous atipamezole. The applied infusion rate (75 microg x kg(-1) x min(-1)) for the highest atipamezole dose was, however, too fast, as evident by transient sympathoactivation. Similar elimination half-lives of these two drugs are a clear advantage considering the possible clinical applications.

Adrenergic alpha-Antagonists↗

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↗