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  • 1
    Online Resource
    Online Resource
    SAGE Publications ; 1999
    In:  Journal of Biological Rhythms Vol. 14, No. 6 ( 1999-12), p. 617-620
    In: Journal of Biological Rhythms, SAGE Publications, Vol. 14, No. 6 ( 1999-12), p. 617-620
    Abstract: The classical power spectrum, computed in the frequency domain, outranks traditionally used periodograms derived in the time domain (such as the [.chi] 2 periodogram) regarding the search for biological rhythms. Unfortunately, classical power spectral analysis is not possible with unequally spaced data (e.g., time series with missing data). The Lomb-Scargle periodogram fixes this shortcoming. However, peak detection in the Lomb-Scargle periodogram of unequally spaced data requires some careful consideration. To guide researchers in the proper evaluation of detected peaks, therefore, a novel procedure and a computer program have recently become available. It is recommended that the Lomb-Scargle periodogram be the default method of periodogram analysis in future biomedical applications of rhythm investigation.
    Type of Medium: Online Resource
    ISSN: 0748-7304 , 1552-4531
    Language: English
    Publisher: SAGE Publications
    Publication Date: 1999
    detail.hit.zdb_id: 2018064-0
    SSG: 12
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  • 2
    In: Biological Rhythm Research, Informa UK Limited, Vol. 32, No. 3 ( 2001-07), p. 347-354
    Type of Medium: Online Resource
    ISSN: 0929-1016 , 1744-4179
    Language: English
    Publisher: Informa UK Limited
    Publication Date: 2001
    detail.hit.zdb_id: 1483040-1
    SSG: 11
    SSG: 12
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  • 3
    Online Resource
    Online Resource
    Informa UK Limited ; 2001
    In:  Biological Rhythm Research Vol. 32, No. 3 ( 2001-07), p. 361-362
    In: Biological Rhythm Research, Informa UK Limited, Vol. 32, No. 3 ( 2001-07), p. 361-362
    Type of Medium: Online Resource
    ISSN: 0929-1016 , 1744-4179
    Language: English
    Publisher: Informa UK Limited
    Publication Date: 2001
    detail.hit.zdb_id: 1483040-1
    SSG: 11
    SSG: 12
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  • 4
    Online Resource
    Online Resource
    Ovid Technologies (Wolters Kluwer Health) ; 2009
    In:  Anesthesia & Analgesia Vol. 108, No. 5 ( 2009-05), p. 1522-1530
    In: Anesthesia & Analgesia, Ovid Technologies (Wolters Kluwer Health), Vol. 108, No. 5 ( 2009-05), p. 1522-1530
    Type of Medium: Online Resource
    ISSN: 0003-2999
    RVK:
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2009
    detail.hit.zdb_id: 2018275-2
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  • 5
    Online Resource
    Online Resource
    Ovid Technologies (Wolters Kluwer Health) ; 2010
    In:  Anesthesia & Analgesia Vol. 110, No. 6 ( 2010-06), p. 1597-1606
    In: Anesthesia & Analgesia, Ovid Technologies (Wolters Kluwer Health), Vol. 110, No. 6 ( 2010-06), p. 1597-1606
    Type of Medium: Online Resource
    ISSN: 0003-2999
    RVK:
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2010
    detail.hit.zdb_id: 2018275-2
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  • 6
    Online Resource
    Online Resource
    Ovid Technologies (Wolters Kluwer Health) ; 2020
    In:  Anesthesiology Vol. 133, No. 6 ( 2020-12-01), p. 1192-1213
    In: Anesthesiology, Ovid Technologies (Wolters Kluwer Health), Vol. 133, No. 6 ( 2020-12-01), p. 1192-1213
    Abstract: Several models describing the pharmacokinetics of ketamine are published with differences in model structure and complexity. A systematic review of the literature was performed, as well as a meta-analysis of pharmacokinetic data and construction of a pharmacokinetic model from raw data sets to qualitatively and quantitatively evaluate existing ketamine pharmacokinetic models and construct a general ketamine pharmacokinetic model. Methods Extracted pharmacokinetic parameters from the literature (volume of distribution and clearance) were standardized to allow comparison among studies. A meta-analysis was performed on studies that performed a mixed-effect analysis to calculate weighted mean parameter values and a meta-regression analysis to determine the influence of covariates on parameter values. A pharmacokinetic population model derived from a subset of raw data sets was constructed and compared with the meta-analytical analysis. Results The meta-analysis was performed on 18 studies (11 conducted in healthy adults, 3 in adult patients, and 5 in pediatric patients). Weighted mean volume of distribution was 252 l/70 kg (95% CI, 200 to 304 l/70 kg). Weighted mean clearance was 79 l/h (at 70 kg; 95% CI, 69 to 90 l/h at 70 kg). No effect of covariates was observed; simulations showed that models based on venous sampling showed substantially higher context-sensitive half-times than those based on arterial sampling. The pharmacokinetic model created from 14 raw data sets consisted of one central arterial compartment with two peripheral compartments linked to two venous delay compartments. Simulations showed that the output of the raw data pharmacokinetic analysis and the meta-analysis were comparable. Conclusions A meta-analytical analysis of ketamine pharmacokinetics was successfully completed despite large heterogeneity in study characteristics. Differences in output of the meta-analytical approach and a combined analysis of 14 raw data sets were small, indicative that the meta-analytical approach gives a clinically applicable approximation of ketamine population parameter estimates and may be used when no raw data sets are available. Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New
    Type of Medium: Online Resource
    ISSN: 0003-3022 , 1528-1175
    RVK:
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2020
    detail.hit.zdb_id: 2016092-6
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  • 7
    In: Anesthesiology, Ovid Technologies (Wolters Kluwer Health), Vol. 98, No. 2 ( 2003-02-01), p. 312-322
    Abstract: Since propofol and remifentanil are frequently combined for monitored anesthesia care, we examined the influence of the separate and combined administration of these agents on cardiorespiratory control and bispectral index in humans. Methods The effect of steady-state concentrations of remifentanil and propofol was assessed in 22 healthy male volunteer subjects. For each subject, measurements were obtained from experiments using remifentanil alone, propofol alone, and remifentanil plus propofol (measured arterial blood concentration range: propofol studies, 0-2.6 microg/ml; remifentanil studies, 0-2.0 ng/ml). Respiratory experiments consisted of ventilatory responses to three to eight increases in end-tidal Pco2 (Petco2). Invasive blood pressure, heart rate, and bispectral index were monitored concurrently. The nature of interaction was assessed by response surface modeling using a population approach with NONMEM. Values are population estimate plus or minus standard error. Results A total of 94 responses were obtained at various drug combinations. When given separately, remifentanil and propofol depressed cardiorespiratory variables in a dose-dependent fashion (resting V(i) : 12.6 +/- 3.3% and 27.7 +/- 3.5% depression at 1 microg/ml propofol and 1 ng/ml remifentanil, respectively; V(i) at fixed Petco of 55 mmHg: 44.3 +/- 3.9% and 57.7 +/- 3.5% depression at 1 microg/ml propofol and 1 ng/ml remifentanil, respectively; blood pressure: 9.9 +/- 1.8% and 3.7 +/- 1.1% depression at 1 microg/ml propofol and 1 ng/ml remifentanil, respectively). When given in combination, their effect on respiration was synergistic (greatest synergy observed for resting V(i)). The effects of both drugs on heart rate and blood pressure were modest, with additive interactions when combined. Over the dose range studied, remifentanil had no effect on bispectral index even when combined with propofol (inert interaction). Conclusions These data show dose-dependent effects on respiration at relatively low concentrations of propofol and remifentanil. When combined, their effect on respiration is strikingly synergistic, resulting in severe respiratory depression.
    Type of Medium: Online Resource
    ISSN: 0003-3022
    RVK:
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2003
    detail.hit.zdb_id: 2016092-6
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  • 8
    Online Resource
    Online Resource
    Ovid Technologies (Wolters Kluwer Health) ; 2013
    In:  Anesthesiology Vol. 119, No. 3 ( 2013-09-01), p. 663-674
    In: Anesthesiology, Ovid Technologies (Wolters Kluwer Health), Vol. 119, No. 3 ( 2013-09-01), p. 663-674
    Abstract: Integrating opioid risk and benefit into a single function may give a useful single measure of the opioid’s positive and negative effects. An explorative study on the effects of fentanyl on antinociception and respiratory depression was performed to construct fentanyl risk–benefit (utility) functions. Methods: Twelve volunteers received a 3.5-μg/kg fentanyl intravenous injection on 2 separate study days. On one occasion, ventilation at a clamped increased carbon dioxide concentration was measured and on another the pain tolerance to electrical stimulation. In both sessions, arterial plasma samples were obtained. The data were analyzed with a population pharmacokinetic–pharmacodynamic model. A simulation study was performed, using the model parameter estimates and their variances, in which simulated subjects received 3.5 μg/kg of fentanyl. The resultant distributions were used to calculate the utility functions, defined as the probability of at least 50% analgesia (an increase in pain tolerance by ≥50%) minus the probability of at least 50% respiratory depression (a reduction in ventilation by ≥50%). Utility functions were constructed in concentration and time domains. Results: Fentanyl produced significant respiratory depression and analgesia. The pharmacokinetic and pharmacodynamic models adequately described the data. The constructed utility functions were negative at effect-site concentrations of greater than 0.5 ng/ml in the first 90 min after the 3.5 μg/kg bolus infusion. Conclusions: Utility functions based on fentanyl’s experimental effects on respiration and pain relief were successfully constructed. These functions are useful in multiple effect comparisons among experimental drugs. Further studies are required to assess whether this risk–benefit analysis is valuable in clinical practice.
    Type of Medium: Online Resource
    ISSN: 0003-3022
    RVK:
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2013
    detail.hit.zdb_id: 2016092-6
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  • 9
    Online Resource
    Online Resource
    Ovid Technologies (Wolters Kluwer Health) ; 1999
    In:  Anesthesiology Vol. 90, No. 4 ( 1999-04-01), p. 1119-1128
    In: Anesthesiology, Ovid Technologies (Wolters Kluwer Health), Vol. 90, No. 4 ( 1999-04-01), p. 1119-1128
    Abstract: Inhalational anesthetics depress breathing dose dependently. The authors studied the dynamics of ventilation on changes in end-tidal sevoflurane partial pressure. To learn more about the mechanisms of sevoflurane-induced respiratory depression, the authors also studied its influence on the dynamic ventilatory response to carbon dioxide. Methods Experiments were performed in cats anesthetized with alpha chloralose-urethane. For protocol 1, step changes in end-tidal sevoflurane partial pressure were applied and inspired ventilation was measured. Breath-to-breath inspired ventilation was related to the sevoflurane concentration in a hypothetical effect compartment based on an inhibitory sigmoid Emax model. For protocol 2, step changes in the end-tidal partial pressure of carbon dioxide were applied at 0, 0.5, and 1% end-tidal sevoflurane. The inspired ventilation-end-tidal partial pressure of carbon dioxide data were analyzed using a two-compartment model of the respiratory controller, which consisted of a fast peripheral and slow central compartment. Values are the mean +/- SD. Results In protocol 1, the effect-site half-life of respiratory changes caused by alterations in end-tidal sevoflurane partial pressure was 3.6+/-1.0 min. In protocol 2, at 0.50% sevoflurane, the central and peripheral carbon dioxide sensitivities decreased to 43+/-20% and 36+/-18% of control. At 1% sevoflurane, the peripheral carbon dioxide sensitivity decreased further, to 12+/-13% of control, whereas the central carbon dioxide sensitivity showed no further decrease. Conclusions Steady state inspired ventilation is reached after 18 min (i.e., 5 half-lives) on stepwise changes in end-tidal sevoflurane. Anesthetic concentrations of sevoflurane have, in addition to an effect on pathways common to the peripheral and central chemoreflex loops, a selective effect on the peripheral chemoreflex loop. Sevoflurane has similar effects on ventilatory control in humans and cats.
    Type of Medium: Online Resource
    ISSN: 0003-3022
    RVK:
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 1999
    detail.hit.zdb_id: 2016092-6
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  • 10
    Online Resource
    Online Resource
    Ovid Technologies (Wolters Kluwer Health) ; 2001
    In:  Anesthesiology Vol. 94, No. 1 ( 2001-01-01), p. 47-55
    In: Anesthesiology, Ovid Technologies (Wolters Kluwer Health), Vol. 94, No. 1 ( 2001-01-01), p. 47-55
    Abstract: Recirculatory models are capable of accurately describing first-pass pharmacokinetics and the influence of cardiac output (CO), which is important for drugs with a fast onset of effect. The influence of CO on pharmacokinetic and pharmacodynamic parameters of rocuronium in patients was evaluated using a recirculatory pharmacokinetic model. Methods Fifteen patients were included to study rocuronium pharmacokinetics and pharmacodynamics. Bolus doses of rocuronium (0.35 mg/kg) and indocyanine green (25 mg) were injected simultaneously via a peripheral intravenous catheter. Blood samples were taken for 240 min from the radial artery. The force of contraction of the adductor pollicis after a train-of-four at 2 Hz every 12 s was measured. Arterial concentration-time curves of rocuronium and indocyanine green were analyzed using a recirculatory model. Pharmacodynamics were described using a sigmoid maximum effect (Emax) model. Results The CO of the patients varied from 2.43 to 5.59 l/min. Total distribution volume of rocuronium was 17.3 +/- 4.8 l (mean +/- SD). The CO showed a correlation with the fast tissue clearance (Cl(T_f); r2 = 0.51), with the slow tissue clearance (Cl(T_s); r2 = 0.31) and with the mean transit times of rocuronium except for the mean transit time of the slow tissue compartment. The blood-effect site equilibration constant (k(e0)) was strongly correlated with CO (r2 = 0.70). Conclusions Cardiac output influences the pharmacokinetics, including k(e0), for rocuronium in patients. For drugs with a fast onset of effect, a recirculatory model, which includes CO, can give a good description of the relation between concentration and effect, in contrast to a conventional compartmental pharmacokinetic model.
    Type of Medium: Online Resource
    ISSN: 0003-3022
    RVK:
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2001
    detail.hit.zdb_id: 2016092-6
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