Modeling the Non–Steady State Respiratory Effects of Remifentanil in Awake and Propofol-sedated Healthy Volunteers

Abstract

The effect of varying remifentanil infusions with and without a background of low-dose propofol on ventilation and end-tidal partial pressure of carbon dioxide concentration was described successfully using a non-steady-state model of the ventilatory control system. The model allows meaningful simulations and predictions.

Modeling Respiratory Depression Induced by Remifentanil and Propofol during Sedation and Analgesia Using a Continuous Noninvasive Measurement of pCO2

“…This is similar to that reported in healthy volunteers (0.92-1.6 ng/ml) (Babenco et al, 2000;Bouillon et al, 2003;Olofsen et al, 2010). Onset of remifentanil effects was slow, with a k e0 of 0.28 minute 21 (t 1/2 k e0 of 2.48 minutes) that increased with age.…”

“…The final model uses the ratio between current and baseline value of pCO 2 as the driving force triggering the regulatory mechanism. Other parameterizations were tested, such as that used by Olofsen et al, (2010), but their parametrization worsened the fit in our case. In addition, we obtained an estimate of the a parameter significantly different from 1 (P , 0.001).…”

“…Feedback mechanisms regulate respiratory drive, which changes the alveolar minute ventilation. This makes it difficult to isolate and quantify key components of the system, and consequently, many of the current models have been developed in highly controlled conditions (Bouillon et al, 1999) and in healthy volunteers (Bouillon et al, 2003(Bouillon et al, , 2004aCaruso et al, 2007;Olofsen et al, 2010). This may limit their ability to predict respiratory depression in patient populations and the clinical environment.…”

“…Few reports exist for models of combined effects of propofol with remifentanil on respiratory depression, despite the frequency with which agents are combined in anesthesia, and those that do are based on data derived from healthy volunteers (Nieuwenhuijs et al, 2003;Olofsen et al, 2010). Respiratory control is determined by multiple processes, in which intrinsic feedback is provided by arterial pH levels and concentrations of O 2 and CO 2 (Lloyd et al, 1958;Dahan et al, 1990;Ward and Karan, 2002).…”

Conscious sedation for awake fibreoptic intubation: a review of the literature

“…There is evidence to suggest that remifentanil sedation administered via TCI provides better conditions and is associated with a lower incidence of complications, such as apnea and respiratory depression, compared with manual administration. [30][31][32] By using TCI, stable effect-site concentrations can be obtained rapidly and maintained for as long as desired, since these devices deliver intravenous drugs using a computer-controlled algorithm that takes into account the drug's particular pharmacokinetic properties. Target-controlled infusion allows the user to achieve a chosen predicted concentration rapidly and with minimal overshoot.…”