Background:Target-controlled infusion is an increasingly common type of administration for propofol. This method requires accurate knowledge of pharmacokinetics, including the effects of age and weight. The authors performed a multicenter population analysis to quantitate the effects of covariates.M

Population pharmacokinetics of propofol: a multicenter study.

Autonomic neuropathy is an important and common complication of Guillain-Barre syndrome (GBS). Manifestations be present in cardiovascular, sudomotor, gastrointestinal and other systems involving both sympathetic and parasympathetic fibers. Some apparently selective acute autonomic neuropathies may be subvarieties of GBS. Experimental work in animal models, pathological studies of GBS patients, and autonomic function studies have provided some help in the understanding of this complication. In managing GBS patients with autonomic dysfunction there are important practical considerations that can improve their care. In this article we review the literature on autonomic neuropathy in GBS and propose a management scheme to accommodate it in the overall treatment of the neuropathy.

Autonomic involvement in Guillain-Barré syndrome : a review

BackgroundThe pharmacology of propofol infusions administered for long-term sedation of intensive care unit (ICU) patients has not been fully characterized. The aim of the study was to develop propofol dosing guidelines for ICU sedation based on an integrated pharmacokinetic–pharmacodynamic model of

Propofol Dosing Regimens for ICU Sedation Based upon an Integrated Pharmacokinetic– Pharmacodynamic Model

BACKGROUND: Movement in response to painful stimulation is the end point classically used to assess the potency of anesthetic agents. In this study, the ability of modeled propofol effect-site concentration to predict movement in volunteers during propofol/nitrous oxide anesthesia was tested, then it was compared with the predictive abilities of the Bispectral Index and 95% spectral edge frequency of the electroencephalogram, pupillary reflex amplitude, and systolic arterial blood pressure. In addition, the relationships between simple end points of loss and recovery of consciousness, and pupillary, hemodynamic, and propofol concentration indicators were studied. METHODS: Ten healthy volunteers were anesthetized with an infusion of propofol, which was increased in three equal steps to 21 mg.kg lean body mass-1.h-1. After loss of the ability to hold a syringe and of the eyelash reflex, 60% nitrous oxide was introduced and the trachea was intubated without the use of muscle relaxants. The propofol infusion rate then was decreased to 15.4 mg.kg lean body mass-1.h-1. Ten minutes later, tetanic electrical stimulation was administered to the thigh via needle electrodes: if movement was observed within 1 min, the propofol infusion rate was increased by 1.75 mg.kg lean body mass-1.h-1 5 min after the stimulus; if not, it was similarly decreased. This 15-min sequence was repeated until volunteers "crossed over" from movement to no movement (or vice versa) four times. The propofol infusion rate then was increased to 21 mg.kg lean body mass-1.h-1, nitrous oxide was discontinued, the trachea was extubated, and the infusion rate was decreased in five equal steps over 50 min. The times at which the eyelash reflex returned and the birth date was recalled were recorded. The electroencephalogram was monitored continuously (FP1, FP2, ref: nasion, ground: mastoid). Measurements of the pupillary response, arterial blood pressure, and heart rate were recorded during induction and awakening, just before and for 5 min after each stimulation. Arterial blood samples were obtained for propofol assay, and propofol effect-site concentrations were calculated at each time. The predictive value of indicators was compared using a new static, the prediction probability (PK). RESULTS: Loss and return of the eyelash reflex occurred at greater propofol effect-site concentrations than either dropping the syringe or recall of the birthday. The propofol effect-site concentration (in the presence of 60% nitrous oxide) predicted to prevent movement after a supramaximal stimulus in 50% of volunteers was 1.80 micrograms/ml (95% confidence limits: 1.40-2.34 micrograms/ml). The Bispectral Index (PK = 0.86), 95% spectral edge frequency (PK = 0.81), pupillary reflex amplitude (PK = 0.74), and systolic arterial blood pressure (PK = 0.78) did not differ significantly from modeled propofol effect-site concentration (PK = 0.76) in their ability to predict movement. CONCLUSIONS: Indicators of pharmacodynamic effect, such as the electroencephalogram, pupillary light reflex, and systolic arterial blood pressure, predict movement as well as effect-site concentration during propofol/nitrous oxide anesthesia. Loss and return of the eyelash reflex correspond to a deeper level of anesthesia than syringe-dropping or recall of the birth date.

Prediction of movement during propofol/nitrous oxide anesthesia. Performance of concentration, electroencephalographic, pupillary, and hemodynamic indicators.

Summary
Ten patients, with a range of illness severity, received a continuous 8-hour infusion of undiluted propofol for sedation while undergoing mechanical ventilation in a general intensive care unit. The level of sedation was assessed hourly and measurements were made of haemodynamic, respiratory, haematological and biochemical variables. Sedation remained satisfactory in most patients throughout the study period, with only occasional alterations in infusion rate, and eight patients required further sedative therapy within 45 minutes of discontinuation of the propofol infusion. Arterial pressure tended to decrease from baseline values; mean and diastolic pressures demonstrated a significant decrease (p < 0.05) at 4, 7 and 8 hours during the infusion. Adrenal steroidogenesis was not inhibited significantly.

Propofol infusion proved to he a useful and readily controllable sedative agent, and discontinuation of the drug was followed by rapid recovery in most cases. The critically ill may be particularly sensitive to the cardiovascular depressant properties of the drug.

Propofol infusion for sedation in intensive care.

A 36 year old man presented with headache, polyuria, thirst and weakness of the lower limbs. Hypertension and a high haematocrit were striking features on initial assessment. Subsequently the full picture of Guillain-Barre syndrome developed. Hormone measurement revealed marked sympathetic nervous system and renin-angiotensin system activation with a return to normal of both blood pressure and hormones with neurological recovery.

https://pmj.bmj.com/content/postgradmedj/61/711/53.full.pdf

Severe hypertension and raised haematocrit: unusual presentation of Guillain-Barré syndrome.

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Severe hypertension and raised haematocrit: unusual presentation of Guillain-Barré syndrome.