Skip to main content
Log in

Gentamicin volume of distribution in critically ill septic patients

  • Originals
  • Published:
Intensive Care Medicine Aims and scope Submit manuscript

Abstract

Gentamicin intrapatient pharmacokinetics variations were studied in 40 critically ill medical patients, suffering gram-negative sepsis. These patients were studied in two phases throughout gentamicin treatment: firstly, on the second day of treatment, when aggressive fluid therapy was required, and secondly, five days later, when patients had achieved a more stable clinical condition. Pharmacokinetic parameters were determined using least squares linear regression analysis assuming a one-compartment model using the Sawchuk-Zaske method. The apparent volume of distribution (Vd) in the first phase of the study was 0.43±0.12 L/kg, while on the seventh day of treatment it was 0.29±0.17 L/kg (p<0.001). Statistically significant differences were also observed for peak serum concentration (p<0.001), total dosage recommended (p<0.001) and half-life (p<0.05), whilst differences were not found for trough levels. From the analysis of the results obtained, we recommend increasing the initial dosage and monitoring plasma levels within the first days of therapy in critically ill patients treated with gentamicin, since important variations in aminoglycoside Vd related to disease, fluid balance and renal function, commonly occur in these patients.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Cunnion RE, Parrillo JE (1989) Miocardial dysfunction in sepsis. Recent insights. Chest 95:941–945

    Google Scholar 

  2. Reilly JM, Cunnion RE, Burch-Witman C, Parker M, Shelhamer JH, Parillo JE (1989) A circulatory myocardial depressant substance is associated with cardiac dysfunction and peripheral hypoperfusion (lactic acidemia) in patients with septic shock. Chest 95:1072–1080

    Google Scholar 

  3. Moore RD, Smith CR, Lietman PS (1984) The association of aminoglycoside plasma levels with mortality in patients with gramnegative bacteremia. J Infect Dis 149:443–448

    Google Scholar 

  4. Summer WR, Michael JR, Lisky JJ (1983) Initial aminoglycoside levels in critically ill. Crit Care Med 11:948–950

    Google Scholar 

  5. Zaske DE, Cipolle RJ, Rotschafter JC (1982) Gentamicin pharmacokinetics in 1640 patients: method for control of serum concentrations. Antimicrob Agents Chemother 21:407–411

    Google Scholar 

  6. Zaske DE, Cipolle RJ, Strate RJ (1980) Gentamicin dosage requirements: wide interpatient variations in 242 surgery patients with normal serum function. Surgery 87:64–69

    Google Scholar 

  7. Mann HJ, Fuhs DW, Awang R, Ndemo FA, Cerra FB (1988) Altered aminoglycoside pharmacokinetics in critically ill patients with sepsis. Clin Pharm 6:148–153

    Google Scholar 

  8. Fuhs DW, Mann HJ, Kubajak CA, Cerra FB (1987) Intrapatient variation of aminoglycoside pharmacokinetics in critically ill surgery patients. Clin Pharm 7:207–213

    Google Scholar 

  9. Triginer C, Fernández R, Izquierdo I, Benito S (1989) Gentamicin pharmacokinetic changes related to mechanical ventilation. Drug Intell Clin Pharm 23:923–924

    Google Scholar 

  10. Garner JS, Jarvis WR, Emori TG, Horan TC, Hughes JM (1988) CDC definitions for nosocomial infections, 1988. Am J Infect Control 16:128–140

    Google Scholar 

  11. Schwartz SN, Pazin GJ, Lyon JA (1978) A controlled investigation of the pharmacokinetics of gentanicin and tobramicin in obese subjects. J Infect Dis 138:499–504

    Google Scholar 

  12. Sawchuk RJ, Zaske DE (1976) Pharmacokinetics of dosing regimens which utilize multiple intravenous infusions. J Pharmacokinet Biopharm 4:183–195

    Google Scholar 

  13. Devine BJ (1974) Gentamicin therapy. Drug Intell Clin Pharm 8:650–655

    Google Scholar 

  14. Zaske DE, Cipolle RJ, Strate RG, Malo JW, Kozalka MS (1980) Rapid gentamicin elimination in obstetrical patients. Obstet Gynecol 56:559–564

    Google Scholar 

  15. Zaske DE, Sawchuk RJ, Gerding DN, Strate RG (1976) Increased dosage requirements of gentamicin in burn patients. J Trauma 16:824–828

    Google Scholar 

  16. Kaojarern S, Maoleekoonpairoj S, Atichartakarn V (1989) Pharmacokinetics of amikacin in hematologic malignancies. Antimicrob Agents Chemother 33:1406–1408

    Google Scholar 

  17. Carr MR, Dick SP, Bordley J, Bertino JB (1988) Gentamicin dosing requirements in patients with acute pancreatitis. Surgery 103:533–537

    Google Scholar 

  18. Schentag JJ, Jusko WJ, Vance JW (1977) Gentamicin disposition and tissue accumulation on multiple dosing. J Pharmacokinet Biopharm 5:559–577

    Google Scholar 

  19. King CH, Creger RJ, Ellner JJ (1985) Pharmacokinetics of tobramycin and gentamicin in abusers of intravenous drugs. Antimicrob Agents Chemother 27:285–290

    Google Scholar 

  20. Koup JR (1989) Disease states and drug pharmacokinetics. J Clin Pharmacol 29:674–679

    Google Scholar 

  21. Mackowiak PA (1989) Influence of fever on pharmacokinetics. Rev Infect Dis 5:804–807

    Google Scholar 

  22. Schentag JJ, Jusko WJ, Vance JW (1977) Gentamicin disposition and tissue accumulation on multiple dosing. J Pharmacokinet Biopharm 5:559–577

    Google Scholar 

  23. Nahata MC, Durrell DE, Miller MA (1986) Accuracy of tobramycin piggyback delivery using gravity flow versus controller. Am J Hosp Pharm 43:947–949

    Google Scholar 

  24. Armistead JA, Nahata MC (1983) Effect of variables associated with intermittent gentamicin infusion on pharmacokinetic predictions. Clin Pharm 2:153–156

    Google Scholar 

  25. Gingell JC, Chisholm GD, Colnan JS (1969) The volume of distribution and excretion of gentamicin with especial reference to renal failure. J Infect Dis 199:396–445

    Google Scholar 

  26. Gyselynck AM, Forrey A Cutler R (1971) Pharmacokinetics of gentamicin; distribution and plasma and renal clearance. J Infec Dis 124:70–76

    Google Scholar 

  27. Niemec PW, Allo MD, Miller CF (1987) Effect of altered volume of distribution on aminoglycoside levels in patients in surgical care. Arch Surg 122:207–211

    Google Scholar 

  28. Weaver RH, Cipolle RJ (1983) Improved aminoglycoside therapy: Clinical application of pharmacokinetic principles. In: Dennis Mungall (ed) Applied clinical pharmacokinetics. Raven Press, New York, pp 153–185

    Google Scholar 

  29. Needleman P, Greenwald JE (1986) Atriopeptin: a cardiac hormone intimately involved in fluid electrolyte, and blood pressure homeostasis. N Engl J Med 314:828–834

    Google Scholar 

  30. Farge D, Payen D (1989) Facteur natriurétique auriculaire (ANF). Aspects physiopathologiques. Réan Soins Intens Méd Urg 5:63–69

    Google Scholar 

  31. Skorecki KL, Leung WM, Campbell P, Warner LC, Wong PY, Bull S, Logan AG, Blendis LM (1988) Role of atrial natriuretic peptide in the natriuretic response to central volume expansion induced by heat-out water immersion in sodium retaining cirrhotic subjects. Am J Med 85:375–382

    Google Scholar 

  32. Winter RJD, Davidson AC, Treacher D, Rudd RM, Anderson JV, Meleagros L, Bloom SR (1989) Atrial natriuretic peptide concentrations in hypoxic secondary pulmonary hypertension: relation to haemodynamic and blood gas variables and response to supplemental oxygen. Thorax 44:58–62

    Google Scholar 

  33. Moore RD, Lietman PS, Smith CR (1987) Clinical response to aminoglycoside therapy: importance of the ratio of peak concentration to minimal inhibitory concentration. J Infect Dis 155:93–99

    Google Scholar 

  34. Vogelman BS, Craig WA (1986) Postantibiotic effects. J Antimicrob Chemother 18:67–73

    Google Scholar 

  35. Craig WA, Vogelman BS (1987) The postantibiotic effect. Ann Intern Med 106:900–902

    Google Scholar 

  36. Hessen MT, Pitsakis PG, Levison ME (1989) Postantibiotic effect of penicillin plus gentamicin versusenterococcus faecalis in vitro and in vivo. Antimicrob Agents Chemother 33:608–611

    Google Scholar 

  37. Sturm AW (1989) Netilmicin in the treatment of Gram-negative Bacteremia: single daily versus multiple daily dosage. J Infect Dis 159:931–937

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Triginer, C., Izquierdo, I., Fernández, R. et al. Gentamicin volume of distribution in critically ill septic patients. Intensive Care Med 16, 303–306 (1990). https://doi.org/10.1007/BF01706354

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01706354

Key words

Navigation