Pharmacokinetics and pharmacokinetic-dynamic modelling of rocuronium in infants and children

Wierda, J. M. K. H.; Meretoja, O. A.; Taivainen, T.; Proost, Johannes H.

doi:10.1093/bja/78.6.690

Cited by 65 publications

(65 citation statements)

References 19 publications

(26 reference statements)

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“…The results of the PK-PD analysis of the clinical study agree well with results found earlier [9,[16][17][18][19]. The observed differences between the present study and earlier studies may be due to differences in the study design, e.g.…”

Section: Discussionsupporting

confidence: 90%

Simultaneous versus sequential pharmacokinetic‐pharmacodynamic population analysis using an Iterative Two‐Stage Bayesian technique

Proost

Schiere

Eleveld

et al. 2007

Biopharm & Drug Disp

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A method for simultaneous pharmacokinetic-pharmacodynamic (PK-PD) population analysis using an Iterative Two-Stage Bayesian (ITSB) algorithm was developed. The method was evaluated using clinical data and Monte Carlo simulations. Data from a clinical study with rocuronium in nine anesthetized patients and data generated by Monte Carlo simulation using a similar study design were analysed by sequential PK-PD analysis, PD analysis with nonparametric PK data and simultaneous PK-PD analysis. Both PK and PD data sets were 'rich' with respect to the number of measurements per individual. The accuracy and precision of the estimated population parameters were evaluated by comparing their mean error (ME) and root mean squared error (RMSE), respectively. The influence of PD model misspecification on the results was also investigated. The simultaneous PK-PD analysis resulted in slightly more precise population parameter estimates than the sequential PK-PD analysis and the nonparametric PK method. In the presence of PD model misspecification, however, simultaneous analysis resulted in poor PK parameter estimates, while sequential PK-PD analysis performed well. In conclusion, ITSB is a valuable technique for PK-PD population analysis of rich data sets. The sequential PK-PD method is better suited for the analysis of rich data than the simultaneous analysis.

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Section: Discussionsupporting

confidence: 90%

Simultaneous versus sequential pharmacokinetic‐pharmacodynamic population analysis using an Iterative Two‐Stage Bayesian technique

Proost

Schiere

Eleveld

et al. 2007

Biopharm & Drug Disp

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show abstract

“…Rocuronium, a nondepolarizing neuromuscular blocker with an action on presynaptic receptors, was used to produce paralysis of muscles below the cuff (5,45). The arm was positioned on a table and compressed by a rubber tube in a disto-proximal direction to minimize blood in the arm, and then the cuff was inflated.…”

Section: Study 3: Movement Prevented By Paralysis With Rocuroniummentioning

confidence: 99%

Signals of motor command bias joint position sense in the presence of feedback from proprioceptors

Smith¹,

Crawford²,

Proske³

et al. 2009

Journal of Applied Physiology

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Joint position sense is believed to be mediated by muscle afferent signals. Because a "phantom" hand produced by a sensory and motor nerve block appears to move in the direction of voluntary effort, signals of "motor command" or "effort" can influence perceived joint position. To determine whether this occurs when sensory signals are available, three studies assessed position sense when motor command and afferent signals were available, but joint movement was prevented. First, the hand was positioned to stop movement at the proximal joint of the middle finger, and movement at the distal joint was impossible because the muscles had been "disengaged". Voluntary efforts produced illusory position changes in the direction of the effort (12.6 +/- 2.0 degrees distal joint; 12.3 +/- 2.3 degrees proximal joint for efforts at 30% maximum; means +/- SD). Second, when subjects attempted to move the index finger under isometric conditions, the index finger appeared to move 7.4 +/- 1.2 degrees in the direction of efforts. These illusions graded with the level of effort (10 or 30% maximum) and far exceeded any real joint movement. Finally, because changes in muscle afferent feedback might have accompanied the voluntary efforts, all forearm and hand muscles were completely paralyzed by locally infused rocuronium. During paralysis, passive wrist position was signaled accurately, but, during attempted efforts (30% maximum), perceived wrist position changed by 9.7 +/- 4.9 degrees . Before paralysis, isometric efforts changed it by 6.7 +/- 3.6 degrees . Thus all studies concur: when joint movement is prevented, signals of motor command contribute to joint position sense.

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“…~,s,6 Although mean recovery times, at equipotent doses, of rocuronium are similar, rocuronium shows prolonged recovery after repeated doses or an accumulative effect. 6 The clinical implication of this accumulative effect is uncertain. Neostigmine has been studied at doses between 30 and 80 ~ag.kg -I for reversal of rocuronium.…”

Section: Discussionmentioning

confidence: 99%

Postoperative reparalysis after rocuronium following nebulized epinephrine

Arndt¹,

Gerry²,

White³

1997

Can J Anaesth

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Postoperative reparalysis after rocuronium following nebulized epinephrinePurpose: We report a case of postoperative reparalysis in the recovery room, following nebulized epinephrine. The patient was pharmacologically reversed with edrophonium after paralysis with rocuronium.Clinical findings: A 12-yr-old girt developed postoperative reparalysis following the intraoperative administration of rocuronium. A total of 0.92 mg.kg -~ rocuronium was administered. After surgery, pharmacological reversal was achieved with 20 mg edrophonium with 0,15 nag. atropine sulfate iv 35 min after the last administration of rocuronium. Muscular relaxation was monitored using an ulnar peripheral nerve stimulator (PNS). After reversal, a full train-of-four and sustained tetanus at 50 Hz were present. In the recovery room, following nebulized epinephrine, the patient became apneic. The patient was paralyzed and an ulnar PNS demonstrated only one faint twitch. The paralysis was reversed with 1.5 mg neostigmine with 0.3 mg glycopyrrolate.Conclusion: Postoperative reparalysis following rocuronium may be a cause of postoperative respiratory distress. The definitive diagnosis is made using PNS and observing the response to pharmacological reversal. Nebulized epinephrine may have a previously undescribed role in the development of postoperative reparalysis.Object.if : Les auteurs d&rivent un cas de recurarisation survenue en salle de r~veil ~ la suite d'une n~bulisation d'EpinEphdne. La curadsation produite par le rocuronium avait &6 neutraJisc~e par I'administration d'~adrophonium.

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Pharmacokinetics and pharmacokinetic-dynamic modelling of rocuronium in infants and children

Cited by 65 publications

References 19 publications

Simultaneous versus sequential pharmacokinetic‐pharmacodynamic population analysis using an Iterative Two‐Stage Bayesian technique

Simultaneous versus sequential pharmacokinetic‐pharmacodynamic population analysis using an Iterative Two‐Stage Bayesian technique

Signals of motor command bias joint position sense in the presence of feedback from proprioceptors

Postoperative reparalysis after rocuronium following nebulized epinephrine

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