Propofol for Monitored Anesthesia Care

Yang

et al. 2011

Korean J Anesthesiol

BackgroundPropofol is used worldwide for its sedative effective; nonetheless, has the serious side effect of respiratory depression. An increased blood concentration of propofol is well known to be associated with increased respiratory depression. However, there are no studies of the effect site concentration inducing respiratory depression. The purpose of this study was to determine the effect site concentration inducing respiratory depression of propofol when sedating a patient after spinal anesthesia.MethodsThis study included thirty seven males who received operations with spinal anesthesia, which was performed on L3-4 and L4-5. All patients were monitored with the bispectral index and were continuously infused with propofol using target controlled infusion. Respiratory depression was diagnosed when one of the following was evident without upper respiratory obstructive signs: a greater than 20% increase of end tidal carbon dioxide from baseline pressure or pulse oximetry oxygen saturation lower than 95%. We obtained the EC5, EC10, and EC50 of the effect site propofol for respiratory depression.ResultsThe EC5 of propofol for respiratory depression was 3.09 mcg/ml (95% CI, 2.60-3.58). The EC10 of propofol for respiratory depression was 3.18 mcg/ml (95% CI, 2.57-3.80). The EC50 of propofol for respiratory depression was 3.99 mcg/ml (95% CI, 2.36-5.61).ConclusionsThe EC5, EC10, and EC50 of effect site propofol for respiratory depression during spinal anesthesia were 3.09 mcg/ml ,3.18 mcg/ml, and 3.99 mcg/ml, respectively.

Section: Discussionmentioning

confidence: 99%

The effect-site concentration of propofol producing respiratory depression during spinal anesthesia

Yang

et al. 2011

Korean J Anesthesiol

“…Propofol is a potent ventilatory depressant. It interferes with ventilation in a dose-dependent manner by affecting central chemoreceptor sensitivity, reducing ventilatory responses to hypercapnia and hypoxia [ 136 – 138 ]. In higher doses, propofol causes apnoea.…”

Section: Pharmacodynamics (Pd)mentioning

confidence: 99%

Clinical Pharmacokinetics and Pharmacodynamics of Propofol

2018

Propofol is an intravenous hypnotic drug that is used for induction and maintenance of sedation and general anaesthesia. It exerts its effects through potentiation of the inhibitory neurotransmitter γ-aminobutyric acid (GABA) at the GABAA receptor, and has gained widespread use due to its favourable drug effect profile. The main adverse effects are disturbances in cardiopulmonary physiology. Due to its narrow therapeutic margin, propofol should only be administered by practitioners trained and experienced in providing general anaesthesia. Many pharmacokinetic (PK) and pharmacodynamic (PD) models for propofol exist. Some are used to inform drug dosing guidelines, and some are also implemented in so-called target-controlled infusion devices, to calculate the infusion rates required for user-defined target plasma or effect-site concentrations. Most of the models were designed for use in a specific and well-defined patient category. However, models applicable in a more general population have recently been developed and published. The most recent example is the general purpose propofol model developed by Eleveld and colleagues. Retrospective predictive performance evaluations show that this model performs as well as, or even better than, PK models developed for specific populations, such as adults, children or the obese; however, prospective evaluation of the model is still required. Propofol undergoes extensive PK and PD interactions with both other hypnotic drugs and opioids. PD interactions are the most clinically significant, and, with other hypnotics, tend to be additive, whereas interactions with opioids tend to be highly synergistic. Response surface modelling provides a tool to gain understanding and explore these complex interactions. Visual displays illustrating the effect of these interactions in real time can aid clinicians in optimal drug dosing while minimizing adverse effects. In this review, we provide an overview of the PK and PD of propofol in order to refresh readers’ knowledge of its clinical applications, while discussing the main avenues of research where significant recent advances have been made.

“…We used the dynamic end-tidal forcing technique to induce steps in end-tidal partial pressures of carbon dioxide (P etco 2 ) and end-tidal PO 2 so that we could study the ventilatory response to isocapnic hypoxia at two levels of P etco 2 . 13 , 14 To that end, the subjects breathed through a mask covering their nose and mouth that was connected to a pneumotachograph and pressure transducer system (Hans Rudolph Inc., USA) to measure ventilation. Additionally, we measured inspired and expired gas concentrations at the mouth using a Masimo Root ISA OR plus capnograph (Masimo, USA).…”

Section: Methodsmentioning

confidence: 99%

“…Intravenous agents such as propofol blunt the response within brainstem respiratory networks. [12][13][14] Still, there is some evidence from small animal studies that at high dose, propofol (6 mg.kg -1 .min -1 ) may have a direct depressant effect at the carotid bodies. 15 To prevent or treat hypoxic events, agnostic respiratory stimulators may be utilized.…”

Section: What This Article Tells Us That Is Newmentioning

confidence: 99%

Reversal of Propofol-induced Depression of the Hypoxic Ventilatory Response by BK-channel Blocker ENA-001: A Randomized Controlled Trial

Jansen,

van Lemmen,

Olofsen

et al. 2024

Anesthesiology

Self Cite

Background The use of anesthetics may result in depression of the hypoxic ventilatory response. Since there are no receptor-specific antagonists for most anesthetics, there is the need for agnostic respiratory stimulants, that increase respiratory drive irrespective of its cause. We tested whether ENA-001, an agnostic respiratory stimulant that blocks carotid body BK-channels, could restore the hypoxic ventilatory response during propofol infusion. We hypothesize that ENA-001 is able to fully restore the hypoxic ventilatory response. Methods In this randomized double-blind cross-over trial, 14 male and female healthy volunteers were randomized to receive placebo, low and high dose ENA-001 on three separate occasions. On each occasion, isohypercapnic hypoxic ventilatory responses were measured during a fixed sequence of placebo, followed by low- and high-dose propofol infusion. We conducted a population pharmacokinetic/pharmacodynamic analysis that included oxygen and carbon dioxide kinetics. Results Twelve subjects completed the three sessions; no serious adverse events occurred. The propofol concentrations were 0.6 and 2.0 µg/mL at low- and high-dose, respectively. The ENA-001 concentrations were 0.6 and 1.0 µg/mL at low- and high-dose, respectively. The propofol concentration that reduced the hypoxic ventilatory response by 50% was 1.47±0.20 µg/mL. The steady-state ENA-001 concentration to increase the depressed ventilatory response by 50% was 0.51±0.04 µg/mL. A concentration of 1 µg/mL ENA-001 was required for full reversal of the propofol effect at its C50. Discussion In this pilot study, we demonstrated that ENA-001 restored the hypoxic ventilatory response impaired by propofol. This finding is not only of clinical importance, but also provides mechanistic insights into the peripheral stimulation of breathing with ENA-001 overcoming central depression by propofol.