Pharmacokinetics of Remifentanil

Description

Intravenous infusion of remifentanil (a strong analgesic) in different rates over varying time periods was applied to a total of 65 patients. Concentration measurements of remifentanil were taken along with several covariates resulting in the Remifentanil data frame with 2107 rows and 12 columns.

Usage

data("Remifentanil", package = "nlme")

Format

This data frame (of class "groupedData", specifically "nfnGroupedData") contains the following columns:

ID:

numerical (patient) IDs.

Subject:

an ordered factor with 65 levels (of the IDs): 30 < 21 < 25 < 23 < 29 < ... ... < 36 < 6 < 5 < 10 < 9.

Time:

time from beginning of infusion in minutes (numeric).

conc:

remifentanil concentration in [ng / ml] (numeric).

Rate:

infusion rate in [µg / min].

Amt:

amount of remifentanil given in the current time interval in [µg].

Age:

age of the patient in years.

Sex:

gender of the patient, a factor with levels Female and Male.

Ht:

height of the patient in cm.

Wt:

weight of the patient in kg.

BSA:

body surface area (DuBois and DuBois 1916): % BSA := Wt^{0.425} \cdot Ht^{0.725} \cdot 0.007184.

LBM:

lean body mass (James 1976), with slightly different formula for men LBM_m := 1.1 Wt - 128 (Wt/Ht)^2, and women LBM_f := 1.07 Wt - 148 (Wt/Ht)^2.

Author(s)

of this help page: Niels Hagenbuch and Martin Maechler, SfS ETH Zurich.

Source

Pinheiro, J. C. and Bates, D. M. (2000). Mixed-Effects Models in S and S-PLUS, Springer, New York.

References

Minto CF, Schnider TW, Egan TD, Youngs E, Lemmens HJM, Gambus PL, Billard V, Hoke JF, Moore KHP, Hermann DJ, Muir KT, Mandema JW, Shafer SL (1997). Influence of age and gender on the pharmacokinetics and pharmacodynamics of remifentanil: I. Model development. Anesthesiology 86 1, 10–23. doi:10.1097/00000542-199701000-00004

Charles F. Minto, Thomas W. Schnider and Steven L. Shafer (1997). Pharmacokinetics and Pharmacodynamics of Remifentanil: II. Model Application. Anesthesiology 86 1, 24–33. doi:10.1097/00000542-199701000-00005

Examples

plot(Remifentanil, type = "l", lwd = 2) # shows the 65 patients' remi profiles

## The same on  log-log  scale  (*more* sensible for modeling ?):
plot(Remifentanil, type = "l", lwd = 2, scales = list(log=TRUE))

str(Remifentanil)
summary(Remifentanil)

plot(xtabs(~Subject, Remifentanil))
summary(unclass(table(Remifentanil$Subject)))
## between 20 and 54 measurements per patient (median: 24; mean: 32.42)

## Only first measurement of each patient :
dim(Remi.1 <- Remifentanil[!duplicated(Remifentanil[,"ID"]),]) #  65 x 12

LBMfn <- function(Wt, Ht, Sex) ifelse(Sex == "Female",
                                        1.07 * Wt - 148*(Wt/Ht)^2,
                                        1.1  * Wt - 128*(Wt/Ht)^2)
with(Remi.1,
     stopifnot(all.equal(BSA, Wt^{0.425} * Ht^{0.725} * 0.007184,
                         tolerance = 1.5e-5),
               all.equal(LBM, LBMfn(Wt, Ht, Sex),
                         tolerance = 7e-7)
))

## Rate: typically  3 µg / kg body weight, but :
sunflowerplot(Rate ~ Wt, Remifentanil)
abline(0,3, lty=2, col=adjustcolor("black", 0.5))