Anesthetics drug pharmacodynamics.

Anesthesia cannot be defined in an unambiguous manner. The essential components of general anesthesia are absence of consciousness and pain. This translates into two particular qualities: (1) sedation and hypnosis, i.e., mental blockade and (2) analgesia/antinociception, i.e., sensory blockade. Anesthetic actions on these two subcomponents are difficult to separate. On the one hand, very few anesthetics act exclusively on one of these components. On the other hand, these components are closely related to each other. Unconsciousness prevents (conscious) perception of pain, and nociception may serve as an arousal stimulus and change the level of sedation and hypnosis. The art of anesthesia lies in adequate dosing of drugs to reach both mental and sensory blockade. Drug administration can be based on pharmacokinetic considerations. Pharmacokinetic models allow an estimation of what happens to the administered drug in the body. Models with an effect site compartment may facilitate a tailored administration of anesthetic drugs. Finally, the quantification of pharmacodynamic effects allows a precise titration of drugs. Clinical assessment of mental blockade is often dichotomous, and therefore not very helpful to guide drug administration. Several scoring systems exist, but once consciousness is lost they become less reliable, in particular because reaction to stimuli is assessed, which mixes assessment of mental blockade with assessment of sensory blockade. Clinical assessment of analgesia requires a conscious patient, so antinociception is difficult to measure. Several methods of objective quantification on the basis of electrical brain activity are discussed including EEG and evoked potentials. Despite numerous indexes of the hypnotic component of anesthesia, there is no parameter that unambiguously quantifies the level of mental or sensory blockade.

[1]  Shanbao Tong,et al.  Advances in quantitative electroencephalogram analysis methods. , 2004, Annual review of biomedical engineering.

[2]  Karen B. Domino,et al.  The Incidence of Awareness During Anesthesia: A Multicenter United States Study , 2004, Anesthesia and analgesia.

[3]  J. Bruhn,et al.  Approximate Entropy as an Electroencephalographic Measure of Anesthetic Drug Effect during Desflurane Anesthesia , 2000, Anesthesiology.

[4]  Hong Ma,et al.  Does the Use of Electroencephalographic Bispectral Index or Auditory Evoked Potential Index Monitoring Facilitate Recovery after Desflurane Anesthesia in the Ambulatory Setting? , 2004, Anesthesiology.

[5]  Erik W. Jensen,et al.  EEG complexity as a measure of depth of anesthesia for patients , 2001, IEEE Trans. Biomed. Eng..

[6]  Gudrun Stockmanns,et al.  Detection of Consciousness by Electroencephalogram and Auditory Evoked Potentials , 2005, Anesthesiology.

[7]  H. Schwilden,et al.  Pharmakodynamik zweier unterschiedlicher Propofolformulierungen , 2006, Der Anaesthesist.

[8]  E. Kochs,et al.  Time Delay of Index Calculation: Analysis of Cerebral State, Bispectral, and Narcotrend Indices , 2006, Anesthesiology.

[9]  D. Chernik,et al.  Validity and Reliability of the Observer's: Assessment of Alertness/Sedation Scale Study with Intravenous Midazolam , 1990, Journal of clinical psychopharmacology.

[10]  C. Lennmarken,et al.  Awareness during anaesthesia: a prospective case study , 2000, The Lancet.

[11]  Christian Jeleazcov,et al.  Electroencephalogram Monitoring During Anesthesia with Propofol and Alfentanil: The Impact of Second Order Spectral Analysis , 2005, Anesthesia and analgesia.

[12]  Philip D Lumb,et al.  Clinical practice guidelines for the sustained use of sedatives and analgesics in the critically ill adult. , 2002, Critical care medicine.

[13]  R N Upton,et al.  A physiological model of induction of anaesthesia with propofol in sheep. 1. Structure and estimation of variables. , 1997, British journal of anaesthesia.

[14]  G Stockmanns,et al.  Wavelet Analysis of Middle Latency Auditory Evoked Responses: Calculation of an Index for Detection of Awareness during Propofol Administration , 2001, Anesthesiology.

[15]  V. Feshchenko,et al.  Drug-induced Amnesia Is a Separate Phenomenon from Sedation: Electrophysiologic Evidence , 2001, Anesthesiology.

[16]  K L Posner,et al.  Awareness during anesthesia: a closed claims analysis. , 1999, Anesthesiology.

[17]  L. Arendt-Nielsen Characteristics, detection, and modulation of laser‐evoked vertex potentials , 1994, Acta anaesthesiologica Scandinavica. Supplementum.

[18]  Steven M. Pincus,et al.  A regularity statistic for medical data analysis , 1991, Journal of Clinical Monitoring.

[19]  H Schwilden,et al.  Closed‐loop Feedback Control of Methohexital Anesthesia by Quantitative EEG Analysis in Humans , 1987, Anesthesiology.

[20]  C. Jeleazcov,et al.  Comparative pharmacokinetics and pharmacodynamics of the new propofol prodrug GPI 15715 and propofol emulsion. , 2004, Anesthesiology.

[21]  I. Rampil,et al.  Changes in EEG spectral edge frequency correlate with the hemodynamic response to laryngoscopy and intubation. , 1987, Anesthesiology.

[22]  I. Rampil A Primer for EEG Signal Processing in Anesthesia , 1998, Anesthesiology.

[23]  Dajun Song,et al.  Is the Bispectral Index Useful in Predicting Fast-Track Eligibility After Ambulatory Anesthesia with Propofol and Desflurane? , 1998, Anesthesia and analgesia.

[24]  K. Kuizenga,et al.  Biphasic EEG changes in relation to loss of consciousness during induction with thiopental, propofol, etomidate, midazolam or sevoflurane. , 2001, British journal of anaesthesia.

[25]  C. Lennmarken,et al.  Victims of awareness , 2002, Acta anaesthesiologica Scandinavica.

[26]  High-frequency components of auditory evoked potentials are detected in responsive but not in unconscious patients. , 2005 .

[27]  Henry Arenbeck,et al.  Signal Verification of Middle Latency Auditory Evoked Potentials by Automated Detection of the Brainstem Response , 2004, Anesthesiology.

[28]  R. Hetherington,et al.  A SIMPLE STUDY OF AWARENESS AND DREAMING DURING ANAESTHESIA , 1970 .

[29]  K. Leslie,et al.  For Personal Use. Only Reproduce with Permission from the Lancet , 2022 .

[30]  T. Salomons,et al.  Pain Flashbacks in Posttraumatic Stress Disorder , 2004, The Clinical journal of pain.

[31]  H Schwilden,et al.  [Investigations on several EEG-parameters as indicators of the state of anaesthesia the median - a quantitative measure of the depth of anaesthesia (author's transl)]. , 1980, Anasthesie, Intensivtherapie, Notfallmedizin.

[32]  C Thornton,et al.  Evoked responses in anaesthesia. , 1998, British journal of anaesthesia.

[33]  R. Treede,et al.  Laser-evoked cerebral potentials in the assessment of cutaneous pain sensitivity in normal subjects and patients. , 1991, Revue neurologique.