Physiologic response of stress and aminoglycoside clearance in critically ill patients

Tholl, Debra A.; Shikuma, Lois R.; Miller, Todd Q.; Woodward, Jean M. B.; Cerra, Frank B.; Zaske, Darwin E.

doi:10.1097/00003246-199302000-00017

Cited by 20 publications

(10 citation statements)

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“…The addition of other physiologic indices did not significantly increase the explanation of this variance, leading to the conclusion that CrCl is the most predictive marker for AG clearance. 31 Patients with sepsis or septic shock often have decreased renal function and increased V. [32][33][34] To highlight the paramount influence of fluctuating CrCl on the PK of AG, a recent article on cardiothoracic surgery has shown that using a sequential interacting multiple model to describe AG concentration-time data from patients with variable renal function fitted the data with higher precision versus a simple multiple model using a single creatinine measurement and a richer data multiple model using all creatinine measurements. 35 This study has some drawbacks, one of which is the retrospective nature of the analysis.…”

Section: Discussionmentioning

confidence: 99%

Suboptimal Aminoglycoside Dosing in Critically Ill Patients

Rea¹,

Capitano²,

Bies³

et al. 2008

Therapeutic Drug Monitoring

127

104

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Maximal aminoglycoside (AG) killing requires that the ratio of peak serum concentrations (Cmax) to the minimum inhibitory concentration (MIC) of the pathogen exceeds by > or =10. This has been shown to hasten resolution of infection in the general patient population. It was postulated that critically ill patients, likely to have larger intravascular volumes, are underdosed. The primary aim was to determine Cmax to MIC target attainment rate in medical intensive care unit (MICU) patients. A retrospective review of MICU patients who received at least 1 intravenous dose and serum concentration of either gentamicin or tobramycin was performed. A population pharmacokinetic model was developed, and MIC distributions for AG were used in determining the Cmax/MIC and in calculating the probability of attaining the pharmacodynamic (PD) target. One hundred two unique patients with 211 AG concentrations were analyzed to determine population pharmacokinetic parameters. Mean maximum clearance (CL) was 3.14L/h (95% confidence interval: 1.26-4.54 L/h), and mean volume of distribution (V) was 53 L (95% confidence interval: 38-66.8 L/h). Glomerular filtration rate and standardized body weight were identified as significant covariates for clearance in the final model. Standardized body weight also significantly affected V. There was only a 20% and 40% probability that patients receiving 7 mg/kg of gentamicin and tobramycin, respectively, will achieve PD target over the range of MIC distributions. Based on these data, the majority of critically ill patients would not be predicted to achieve the PD target under current dosing regimens. This may be a result of intensive care unit patients having a larger volume of distribution than reported in the literature. Future recommendations for treating gram-negative infections in the MICU population include using initial doses of 7 mg/kg of either gentamicin or tobramycin, measuring Cmax after the first dose, and determining MIC for the pathogen(s) with adjustment of subsequent doses to achieve the PD target.

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Section: Discussionmentioning

confidence: 99%

Suboptimal Aminoglycoside Dosing in Critically Ill Patients

Rea¹,

Capitano²,

Bies³

et al. 2008

Therapeutic Drug Monitoring

127

104

View full text Add to dashboard Cite

show abstract

“…Clearance values of gentamicin were not reported. Another paper has demonstrated significant correlation between gentamicin and creatinine clearance in critically ill patients (19).…”

Section: Critical Illnessmentioning

confidence: 99%

Gentamicin dosing in critically ill patients

Hansen¹,

Christrup²,

Jarlov

et al. 2001

Acta Anaesthesiol Scand

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Gentamicin is used worldwide in the treatment of serious infections in critically ill patients. The therapeutic efficacy of gentamicin is correlated to the peak serum concentration and the adverse effects to the trough concentrations. Information concerning the pharmacodynamics in critically ill patients is scarce, but pharmacokinetic data are available. A once-daily dosage regimen has replaced multiple dosing of gentamicin in most intensive care units. No studies evaluating the superiority of either of these dosage recommendations in critically ill patients have ever been conducted. Based on 8 meta-analyses performed addressing this issue on a wide range of patients and theoretical considerations, we consider a once-daily dosage regimen feasible in critically ill patients. In septic patients the volume of distribution is significantly increased compared to normal patients, implying that the initial dose should be increased in this patient population. Additionally a general trend towards using higher loading doses (5-7 mg/kg) has been observed in USA, and the appropriateness of this dosing strategy is based on a large descriptive American study. We recommend that the initial dosage of gentamicin in critically ill hyperdynamic septic patients should be 7 mg/kg. Optimal and appropriate monitoring of the treatment with gentamicin in the critically ill patient is still an issue for further investigation. The treatment period with gentamicin should be short (3-5 days), bearing the pharmacological properties of aminoglycosides (small volume of distribution and poor tissue penetration) in mind. In patients with reduced renal function the initial dose of gentamicin should also be increased and maintenance dose reduced preferentially by prolonging the dosing intervals. However, the use of aminoglycosides in a high dose regimen in oliguric or anuric patients or patients who present with a rapidly decreasing renal function needs further consideration.

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“…The addition of other physiological indices did not significantly increase the explanation of this variance, leading to the conclusion that CL CR is the most predictive marker for AG clearance. 54 Patients with sepsis or septic shock often have abnormal renal or hepatic function leading to decreased urine output and may have abnormal Vd because they are not able to excrete the amount of fluid that they are receiving. [55][56][57] Alternatively, in the absence of organ dysfunction, sepsis can increase renal preload and lead to third-spacing via increased capillary permeability resulting in higher antibacterial clearances.…”

Section: Aminoglycoside Pharmacokinetics In the Critically Illmentioning

confidence: 99%

Optimizing Use of Aminoglycosides in the Critically Ill

Rea

Capitano²

2007

Semin Respir Crit Care Med

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In the era of increasing bacterial resistance and a lack of development of new antimicrobials for the treatment of gram-negative infections, aminoglycosides (AGs) are more commonly used in combination with other antimicrobials for the treatment of life-threatening infections in the intensive care unit (ICU). AGs display concentration-dependent killing activity; thus the rate and extent of bacterial killing increase with increasing peak (Cmax) drug concentrations. Optimizing AG dosing requires attainment of a pharmacodynamic target ratio (Cmax:minimal inhibitory concentration [MIC] > or = 10) upon first dose, which is associated with a more rapid rate of resolution of infection. Extended-interval AG dosing has been shown to attain this target in the general patient population while decreasing the risk of nephrotoxicity compared with multiple daily dosing. However, ICU patients have pharmacokinetic differences compared with patients who are less ill, including increased volume of distribution and variable clearance, which may make attainment of this target difficult. The need for extended-interval aminoglycoside dosing with Cmax monitoring and MIC determination of the pathogen may be needed to optimally treat serious infections in the critically ill.

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Physiologic response of stress and aminoglycoside clearance in critically ill patients

Cited by 20 publications

References 0 publications

Suboptimal Aminoglycoside Dosing in Critically Ill Patients

Suboptimal Aminoglycoside Dosing in Critically Ill Patients

Gentamicin dosing in critically ill patients

Optimizing Use of Aminoglycosides in the Critically Ill

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