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A sound engineer at a music company recently encountered a problem. The output from their newly acquired studio's vintage mixing console was too low for the requirements of modern recording equipment. To rectify this situation, the engineer decided to design an audio pre-amplifier using an operational amplifier (op-amp) to boost the signal level.
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The concept of mixing time is significant in producing a uniform concrete mix with the required strength. The mixing period starts once all components are in the mixer. Initially, the mixer is charged with 10% of the water, followed by the consistent addition of solids and then 80% of the water. The remaining water is added later, within the first quarter of the mixing period. The minimum mixing time varies according to the mixer's capacity; for example, mixers with up to 1 cubic yard...
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De-mystifying the "Mixifusor".

Anthony R Absalom1, Ann E Rigby-Jones2, Andrew R Rushton3

  • 1University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.

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Summary
This summary is machine-generated.

Mixing propofol and remifentanil for total intravenous anesthesia (TIVA) poses significant risks. This practice, despite perceived acceptance, is not recommended due to pharmaceutical, pharmacokinetic, and medicolegal concerns.

Keywords:
clinical pharmacologypharmacokineticspropofolremifentanilsafetytarget-controlled infusions

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Area of Science:

  • Anesthesiology
  • Pharmacology
  • Pharmaceutical Science

Background:

  • Total intravenous anesthesia (TIVA) using a mixture of propofol and remifentanil in the same syringe is an accepted technique in Pediatric Anesthesia.
  • A UK survey indicated a low incidence of serious complications with this method.
  • However, current guidelines for safe TIVA recommend against this practice due to several concerns.

Purpose of the Study:

  • To evaluate the pharmaceutical, pharmacokinetic, and medicolegal implications of mixing propofol and remifentanil for TIVA.
  • To highlight the risks associated with administering combined propofol-remifentanil infusions.
  • To inform clinical practice and adherence to safety guidelines.

Main Methods:

  • Review of pharmaceutical concerns regarding the physical stability, concentration changes, mixing uniformity, and contamination risk of propofol-remifentanil mixtures.
  • Pharmacokinetic modeling to illustrate the consequences of delivering remifentanil passively via a propofol target-controlled infusion (TCI).
  • Analysis of clinical consequences based on the dose-dependent pharmacodynamics of remifentanil and medicolegal considerations under UK and EU law.

Main Results:

  • Pharmaceutical concerns include emulsion instability, concentration variability, nonuniform mixing, contamination risk, and potential administration errors.
  • Pharmacokinetic modeling reveals that remifentanil delivery is not target-controlled, leading to unpredictable peaks and troughs in concentration.
  • Clinical consequences include risks of apnea, bradycardia, hypotension, inadequate narcosis, and unwanted surgical responses, with inflexible dosing.

Conclusions:

  • Mixing propofol and remifentanil creates an unlicensed drug, placing the clinician in the position of a manufacturer.
  • The practice carries significant medicolegal risks, potentially leading to legal challenges and regulatory scrutiny in case of patient harm.
  • Clinicians should adhere to guidelines recommending against the co-administration of propofol and remifentanil in the same syringe for TIVA.