Article: Influence of serum protein, serum albumin concentrations and dose on midazolam anaesthesia induction times

Individual variation occurs in time to induction of anaesthesia with intravenous drugs. Less free drug is available to cross the blood-brain barrier when the drug is highly protein bound. Since this may prolong time to sleep, we correlated the induction time, serum albumin and total protein concentrations, and doses of midazolam, which is a highly protein bound intravenous anaesthetic. There is a poor correlation (r = 0.062) between induction time and serum protein, a weak (r = 0.542) but statistically significant (p = 0.026) correlation between induction time and serum albumin, and a highly significant (p = 0.003) negative correlation (r = 0.579) between drug dose and induction time. The administration of the appropriate dose of midazolam for induction, therefore, appears to affect induction time more significantly than does the serum albumin concentration.

Citing Articles

Sedative and Analgesic Pharmacokinetics During Pediatric ECMO.

Zimmerman K, Dallefeld S, Hornik C, Watt K J Pediatr Pharmacol Ther. 2020; 25(8):675-688.

PMID: 33214778 PMC: 7671016. DOI: 10.5863/1551-6776-25.8.675.

Albumin as a drug: its biological effects beyond volume expansion.

Bihari S, Bannard-Smith J, Bellomo R Crit Care Resusc. 2020; 22(3):257-265.

PMID: 32900333 PMC: 10692529.

Effect of the ethinylestradiol/levonorgestrel combined oral contraceptive on the activity of cytochrome P4503A in obese women.

Edelman A, Munar M, Elman M, Koop D, Cherala G Br J Clin Pharmacol. 2012; 74(3):510-4.

PMID: 22299599 PMC: 3477352. DOI: 10.1111/j.1365-2125.2012.04209.x.

Propofol increases the rate of albumin-unbound free midazolam in serum albumin solution.

Ohmori J, Maeda S, Higuchi H, Ishii M, Arai Y, Tomoyasu Y J Anesth. 2011; 25(4):618-20.

PMID: 21630018 DOI: 10.1007/s00540-011-1176-6.

Debate: Albumin administration should be avoided in the critically ill.

Pulimood T, Park G Crit Care. 2001; 4(3):151-5.

PMID: 11211856 PMC: 137253. DOI: 10.1186/cc688.

References

1.

Halperin M, Blackwelder W, Verter J . Estimation of the multivariate logistic risk function: a comparison of the discriminant function and maximum likelihood approaches. J Chronic Dis. 1971; 24(2):125-58. DOI: 10.1016/0021-9681(71)90106-8. View

2.

Norman J . Drug-receptor reactions. Br J Anaesth. 1979; 51(7):595-601. DOI: 10.1093/bja/51.7.595. View

3.

Fragen R, Gahl F, Caldwell N . A water-soluble benzodiazepine, RO21-3981, for induction of anesthesia. Anesthesiology. 1978; 49(1):41-3. DOI: 10.1097/00000542-197807000-00012. View

4.

HUG Jr C . Pharmacokinetics of drugs administered intravenously. Anesth Analg. 1978; 57(6):704-23. DOI: 10.1213/00000539-197811000-00020. View

5.

Stella L, Torri G, Castiglioni C . The relative potencies of thiopentone, ketamine, propanidid, alphaxalone and diazepam. A statistical study in man. Br J Anaesth. 1979; 51(2):119-22. DOI: 10.1093/bja/51.2.119. View

6.

Levy G . Effects of plasma protein binding of drugs on duration and intensity of pharmacological activity. J Pharm Sci. 1976; 65(8):1264-5. DOI: 10.1002/jps.2600650837. View

7.

Reves J, CORSSEN G, Holcomb C . Comparison of two benzodiazepines for anaesthesia induction: midazolam and diazepam. Can Anaesth Soc J. 1978; 25(3):211-4. DOI: 10.1007/BF03004881. View

8.

Conner J, Katz R, PAGANO R, Graham C . RO 21-3981 for intravenous surgical premedication and induction of anesthesia. Anesth Analg. 1978; 57(1):1-5. DOI: 10.1213/00000539-197801000-00001. View

9.

Dundee J . New i.v. anaesthetics. Br J Anaesth. 1979; 51(7):641-8. DOI: 10.1093/bja/51.7.641. View

10.

Reves J, Kissin I, Smith L . The effective dose of midazolam. Anesthesiology. 1981; 55(1):82. DOI: 10.1097/00000542-198107000-00019. View

11.

Hull C . Pharmacokinetics and pharmacodynamics. Br J Anaesth. 1979; 51(7):579-94. DOI: 10.1093/bja/51.7.579. View

12.

McNamara P, Levy G, Gibaldi M . Effect of plasma protein and tissue binding on the time course of drug concentration in plasma. J Pharmacokinet Biopharm. 2010; 7(2):195-206. DOI: 10.1007/BF01059738. View

13.

Reves J, Vinik R, Hirschfield A, Holcomb C, Strong S . Midazolam compared with thiopentone as a hypnotic component in balanced anaesthesia: a randomized, double-blind study. Can Anaesth Soc J. 1979; 26(1):42-9. DOI: 10.1007/BF03039453. View

Influence of Serum Protein, Serum Albumin Concentrations and Dose on Midazolam Anaesthesia Induction Times