Sequestration of fentanyl by the cardiopulmonary bypass (CPBP)

Koren, Gideon; Crean, Peter; Klein, Julia; Goresky, Gerald V.; Villamater, J.; MacLeod, S. M.

doi:10.1007/bf02395206

Cited by 68 publications

(31 citation statements)

References 17 publications

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“…In our study, the dilutional effect of CPB was estimated as a percentage of total volume as suggested by Koren et al (17). Total volume was calculated by adding the priming volume to an assumed blood volume of 80 ml/kg of body weight (8).…”

Section: Resultsmentioning

confidence: 99%

Effect of cardiopulmonary bypass on vancomycin and netilmicin disposition

Klamerus

Rodvold

Silverman

et al. 1988

Antimicrob Agents Chemother

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The effect of cardiopulmonary bypass (CPB) on the disposition of vancomycin (15 mg/kg) and of netilmicin (3 mg/kg) was studied in 10 adults. The concentration-time profile of the drug in serum and renal clearance were characterized pre-CPB, during CPB, and post-CPB. Vancomycin and netilmicin exhibited initial decreases in mean concentrations in serum of 4.0 mg/liter (16.8%) and 2.2 mg/liter (29.1%), respectively, upon initiation of CPB. Netilmicin concentrations in serum rebounded to a mean of 0.6 mg/liter (15.4%) within 90 min on CPB and then continuously decreased. Vancomycin concentrations in serum demonstrated a rebound increase of 2.3 mg/liter (23.5%) at the end of CPB when the aorta was unclamped. Mean renal clearance throughout CPB was decreased for vancomycin (58.4 to 43.4 ml/min per mi2) and netilmicin (53.4 to 31.5 ml/min per m2). The rebound in vancomycin concentration in serum strongly correlated with the length of time between unclamping the aorta and coming off CPB (r = 0.94), as well as with the increase in temperature upon rewarming (r = 0.92).Antimicrobial prophylaxis for cardiopulmonary bypass (CPB) surgery is routinely prescribed to prevent endocarditis or sternal and costochondral infections (7, 26). Selection of an appropriate antibiotic is directed against Staphylococcus aureus and Staphylococcus epidermidis, which account for the majority of bacterial infections, and also against the gram-negative bacilli (2, 3, 7, 26). The increasing incidence of methicillin-resistant staphylococci has led to the recommendation that vancomycin be administered prophylactically for cardiothoracic surgery in hospitals in which methicillin-resistant staphylococci are prevalent (3,15,16). Aminoglycosides have been recommended for prophylaxis against the gram-negative pathogens on the cardiac valves and the sternum and for some prophylactic effect against staphylococci (16).Many physiologic changes occur in patients placed on CPB. These changes, including decreased cardiac output and organ perfusion, can alter drug absorption, distribution, metabolism, and excretion (13,14). Studies with prophylactic vancomycin and netilmicin in CPB surgery are very limited. Only two reports have examined vancomycin concentrations in serum during CPB surgery, and both sought to determine appropriate dosing, rather than drug disposition (4, 10).One published report of aminoglycoside prophylaxis in open-heart surgery has addressed netilmicin concentrations in pericardial fluid, atrial appendage, and serum but only in the intraoperative phase of CPB (27). Therefore, this study was designed to investigate what effect CPB surgery has on the disposition of two renally excreted prophylactic antibiotics, vancomycin and netilmicin, before, during, and after CPB. MATERIALS AND METHODSA total of 10 adult patients scheduled for elective coronary artery bypass grafting or cardiac valve replacement surgery requiring CPB were studied. All patients gave written informed consent to participate in this protocol, which was * Corresponding author....

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Section: Resultsmentioning

confidence: 99%

Effect of cardiopulmonary bypass on vancomycin and netilmicin disposition

Klamerus

Rodvold

Silverman

et al. 1988

Antimicrob Agents Chemother

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“…Previous studies have measured total fentanyl concentrations in plasma and reported a significant drop on connection to bypass (4)(5)(6). Fentanyl is usually about 80% bound to plasma proteins but this is likely to vary under abnormal physiological conditions (7).…”

Section: Introductionmentioning

confidence: 99%

Effect of cardiopulmonary bypass on the plasma concentrations of fentanyl and alcuronium

Miller

Peterson

McLean

et al. 1997

Journal of Clinical Pharmacy and Therapeutics

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This study was conducted to examine the effect of cardiopulmonary bypass surgery on the total and unbound plasma concentrations of fentanyl and the total plasma concentrations of alcuronium. Total fentanyl concentrations were measured by gas chromatography, the plasma protein binding of fentanyl by ultrafiltration, and alcuronium concentrations by high-performance liquid chromatography. Sixteen patients were studied. On initiation of cardiopulmonary bypass (CPB), there were mean decreases of 58.8 +/- 7.1% and 47 +/- 3.2% for total concentrations of fentanyl in plasma and haemoglobin in blood, respectively. The magnitude of these reductions in individual patients was significantly related (Spearman p = 0.65, P < 0.05). The unbound fraction of fentanyl rose from 0.23 to 0.34 after the start of CPB. The total fentanyl concentration remained relatively stable during bypass until near the end of CPB when the mean total concentration increased, coinciding with rewarming. The size of the increase was related to the body mass index (BMI) of the patient (Spearman p = 0.85, P < 0.01). The estimated elimination half-life of fentanyl using the grouped data was 4.7 h. The total alcuronium concentration in plasma fell by 29% on initiation of CPB and there was no increase on rewarming. The estimated elimination half-life of alcuronium using the grouped data was 234 min. Despite marked declines in the plasma concentrations of both drugs on initiation of CPB, suitable levels of anaesthesia were maintained throughout the procedure.

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“…Many physiological changes occur in patients placed on CBP, and this technique is known to alter drug levels in plasma (8,15). At least two factors can explain this result: a rapid increase in the volume of distribution because of the additional volume in the priming pump (11) and drug sequestration within the CPB circuit, which has been demonstrated for fentanyl (8) and nitroglycerin (5) but is only suspected for vancomycin (10). Whatever the mechanism, plasma vancomycin concentrations decrease when the patient is placed on CPB.…”

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confidence: 99%

Penetration of vancomycin into mediastinal and cardiac tissues in humans

Martin

Alaya

Mallet

et al. 1994

Antimicrob Agents Chemother

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Vancomycin penetration into heart tissues (valves, myocardium, auricles, and pericardium) and mediastinal tissues (fat and sternal bone) was evaluated after two regimens of vancomycin administration. Ten patients were given 15 mg of vancomycin per kg of body weight before anesthesia. Ten other patients received the same dose and then a second 7.5-mg/kg dose at the time of initiation of cardiopulmonary bypass. Similar and satisfactory vancomycin tissue penetrations were observed in both groups. However, for some patients in the two groups, vancomycin levels in tissue were less than the MICs for potential pathogens (Staphylococcus aureus and Staphylococcus epidermidis).Cardiac surgery is a clean surgery but requires antibiotic prophylaxis to prevent serious postoperative infections of the cardiac valves or the mediastinal tissues (1). Antibiotic prophylaxis is used to protect against pathogens most likely to contaminate the surgical wound, that is, methicillin-resistant or susceptible staphylococci. Cephalosporins (cefazolin, cefamandole) are widely used for that purpose, but vancomycin is an alternative for prophylaxis in allergic patients or when a risk of postoperative infections because of methicillin-resistant staphylococci exists (6,8). Vancomycin is characterized by a slow killing rate of bacteria, and this is particularly true for low levels of the drug (half the MIC) (16). Given this time dependency for bacterial killing, exposure of bacteria to antibiotic concentrations greater than the MIC for long periods of time seems desirable. For prophylaxis for postoperative infections, such adequate antibiotic concentrations should probably be achieved in all potential sites of infection (2, 13).The present study was designed to determine whether two different dose regimens could result in the achievement and maintenance of adequate concentrations in sternal bone, mediastinal fat, and heart tissues. Levels in tissue greater than or equal to the MIC for 90% of methicillin-susceptible or resistant Staphylococcus aureus (1 ,ug/ml) and coagulase-negative staphylococci (2 ,ug/ml) tested (19) were considered adequate.Subject and study design. The study received the approval of the Ethics Committee of our institution (Hopital Nord), and all patients gave informed consent. The study was prospective and randomized and was designed to compare the penetration of vancomycin after either a single (group 1) or two (group 2) intraoperative intravenous doses in patients undergoing mitral or aortic valve replacement. Twenty patients, divided into two groups of 10 patients each, were included in the study. Criteria for inclusion were as follows: 18 years of age or older, absence of prior history of hepatic or renal disease, elective surgery, and no clinical or laboratory signs of infection. Antibiotic administration. Group administered intravenously over a 60-min period. Infusion was started 90 min before the surgical incision. Group 2 patients were given the same dose following the same protocol. A second dose of vancomycin (7....

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Sequestration of fentanyl by the cardiopulmonary bypass (CPBP)

Cited by 68 publications

References 17 publications

Effect of cardiopulmonary bypass on vancomycin and netilmicin disposition

Effect of cardiopulmonary bypass on vancomycin and netilmicin disposition

Effect of cardiopulmonary bypass on the plasma concentrations of fentanyl and alcuronium

Penetration of vancomycin into mediastinal and cardiac tissues in humans

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