Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
BMC Anesthesiology
Published in: BMC Anesthesiology 1/2012

Open Access 01-12-2012 | Study protocol

ASAP ECMO: Antibiotic, Sedative and Analgesic Pharmacokinetics during Extracorporeal Membrane Oxygenation: a multi-centre study to optimise drug therapy during ECMO

Authors: Kiran Shekar, Jason A Roberts, Susan Welch, Hergen Buscher, Sam Rudham, Fay Burrows, Sussan Ghassabian, Steven C Wallis, Bianca Levkovich, Vin Pellegrino, Shay McGuinness, Rachael Parke, Eileen Gilder, Adrian G Barnett, James Walsham, Daniel V Mullany, Yoke L Fung, Maree T Smith, John F Fraser

Published in: BMC Anesthesiology | Issue 1/2012

Login to get access

Abstract

Background

Given the expanding scope of extracorporeal membrane oxygenation (ECMO) and its variable impact on drug pharmacokinetics as observed in neonatal studies, it is imperative that the effects of the device on the drugs commonly prescribed in the intensive care unit (ICU) are further investigated. Currently, there are no data to confirm the appropriateness of standard drug dosing in adult patients on ECMO. Ineffective drug regimens in these critically ill patients can seriously worsen patient outcomes. This study was designed to describe the pharmacokinetics of the commonly used antibiotic, analgesic and sedative drugs in adult patients receiving ECMO.

Methods/Design

This is a multi-centre, open-label, descriptive pharmacokinetic (PK) study. Eligible patients will be adults treated with ECMO for severe cardiac and/or respiratory failure at five Intensive Care Units in Australia and New Zealand. Patients will receive the study drugs as part of their routine management. Blood samples will be taken from indwelling catheters to investigate plasma concentrations of several antibiotics (ceftriaxone, meropenem, vancomycin, ciprofloxacin, gentamicin, piperacillin-tazobactum, ticarcillin-clavulunate, linezolid, fluconazole, voriconazole, caspofungin, oseltamivir), sedatives and analgesics (midazolam, morphine, fentanyl, propofol, dexmedetomidine, thiopentone). The PK of each drug will be characterised to determine the variability of PK in these patients and to develop dosing guidelines for prescription during ECMO.

Discussion

The evidence-based dosing algorithms generated from this analysis can be evaluated in later clinical studies. This knowledge is vitally important for optimising pharmacotherapy in these most severely ill patients to maximise the opportunity for therapeutic success and minimise the risk of therapeutic failure.

Trial registration

ACTRN12612000559819
Appendix
Available only for authorised users
Literature
1.
Fraser JF, Shekar K, Diab S, Foley SR, McDonald CI, Passmore M, Simonova G, Roberts JA, Platts DG, Mullany DV, Fung YL: ECMO - the clinician's view. ISBT Science Series. 2012, 7: 82-88. 10.1111/j.1751-2824.2012.01560.x.CrossRef
2.
Beckmann A, Benk C, Beyersdorf F, Haimerl G, Merkle F, Mestres C, Pepper J, Wahba A: Position article for the use of extracorporeal life support in adult patients. Eur J Cardiothorac Surg. 2011, 40 (3): 676-680.PubMed
3.
MacLaren G, Combes A, Bartlett RH: Contemporary extracorporeal membrane oxygenation for adult respiratory failure: life support in the new era. Intensive Care Med. 2012, 38 (2): 210-220. 10.1007/s00134-011-2439-2.CrossRefPubMed
4.
ECLS Registry report: Extracorporeal Life Support Organisation. 2011, Ann Arbor( MI)
5.
Davies A, Jones D, Bailey M, Beca J, Bellomo R, Blackwell N, Forrest P, Gattas D, Granger E, Herkes R, et al: Extracorporeal membrane oxygenation for 2009 influenza a(H1N1) acute respiratory distress syndrome. JAMA. 2009, 302 (17): 1888-1895.CrossRefPubMed
6.
Peek GJ, Mugford M, Tiruvoipati R, Wilson A, Allen E, Thalanany MM, Hibbert CL, Truesdale A, Clemens F, Cooper N, et al: Efficacy and economic assessment of conventional ventilatory support versus extracorporeal membrane oxygenation for severe adult respiratory failure (CESAR): a multicentre randomised controlled trial. Lancet. 2009, 374 (9698): 1351-1363. 10.1016/S0140-6736(09)61069-2.CrossRefPubMed
7.
8.
Roberts DM, Roberts JA, Roberts MS, Liu X, Nair P, Cole L, Lipman J, Bellomo R: Variability of antibiotic concentrations in critically ill patients receiving continuous renal replacement therapy – a multicentre pharmacokinetic study. Crit Care Med. 2012, 40 (5): 1523-1528. 10.1097/CCM.0b013e318241e553.CrossRefPubMed
9.
Udy AA, Varghese JM, Altukroni M, Briscoe S, McWhinney B, Ungerer J, Lipman J, Roberts JA: Sub-therapeutic initial beta-lactam concentrations in select critically ill patients: association between augmented renal clearance and low trough drug concentrations. Chest. 2012, 142 (1): 30-39. 10.1378/chest.11-1671.CrossRefPubMed
10.
Patel K, Roberts JA, Lipman J, Tett SE, Deldot ME, Kirkpatrick CM: Population pharmacokinetics of fluconazole in critically ill patients receiving continuous venovenous hemodiafiltration: using monte carlo simulations to predict doses for specified pharmacodynamic targets. Antimicrob Agents Chemother. 2011, 55 (12): 5868-5873. 10.1128/AAC.00424-11.CrossRefPubMedPubMedCentral
11.
Roberts JA, Taccone FS, Udy AA, Vincent JL, Jacobs F, Lipman J: Vancomycin dosing in critically ill patients: robust methods for improved continuous-infusion regimens. Antimicrob Agents Chemother. 2011, 55 (6): 2704-2709. 10.1128/AAC.01708-10.CrossRefPubMedPubMedCentral
12.
Shekar K, Fraser JF, Smith MT, Roberts JA: Pharmacokinetic changes in patients receiving extracorporeal membrane oxygenation. J Crit Care. 2012, Epub ahed of print
13.
Buck ML: Pharmacokinetic changes during extracorporeal membrane oxygenation: implications for drug therapy of neonates. Clin Pharmacokinet. 2003, 42 (5): 403-417. 10.2165/00003088-200342050-00001.CrossRefPubMed
14.
Alcorn J, McNamara PJ: Pharmacokinetics in the newborn. Adv Drug Deliv Rev. 2003, 55 (5): 667-686. 10.1016/S0169-409X(03)00030-9.CrossRefPubMed
15.
Shekar K, Roberts JA, Mullany DV, Corley A, Fisquet S, Bull TN, Barnett AG, Roberts JA, Fraser JF: Increased sedation requirements in patients receiving extracorporeal membrane oxygenation for respiratory and cardio-respiratory failure. Anaesth Intensive Care. 2012, 40: 648-655.PubMed
16.
Shekar K, Roberts JA, Ghassabian S, Mullany DV, Ziegenfuss M, Smith MT, Fung YL, Fraser JF: Sedation during extracorporeal membrane oxygenation –why more is less?. Anaesth Intensive Care. 2012, 40: 6-
17.
Mulla HGL, Firmin RK, David RU: Drug disposition during extracorporeal membrane oxygenation (ECMO). Paediatric and Perinatal Drug Therapy. 2001, 4 (3): 109-120.
18.
Shekar K, Roberts JA, Mcdonald CI, Fisquet S, Barnett AG, Mullany DV, Ghassabian S, Fung YL, Smith MT, Fraser JF: Sequestration of drugs in the circuit may lead to therapeutic failure during extracorporeal membrane oxygenation. Crit Care. 2012, 16 (5): R194-10.1186/cc11679. Epub ahead of printCrossRefPubMedPubMedCentral
19.
Wildschut ED, Ahsman MJ, Allegaert K, Mathot RA, Tibboel D: Determinants of drug absorption in different ECMO circuits. Intensive Care Med. 2010, 36 (12): 2109-2116. 10.1007/s00134-010-2041-z.CrossRefPubMedPubMedCentral
20.
Bhatt-Mehta V, Johnson CE, Schumacher RE: Gentamicin pharmacokinetics in term neonates receiving extracorporeal membrane oxygenation. Pharmacotherapy. 1992, 12 (1): 28-32.PubMed
21.
Rosen DA, Rosen KR, Silvasi DL: In vitro variability in fentanyl absorption by different membrane oxygenators. J Cardiothorac Anesth. 1990, 4 (3): 332-335. 10.1016/0888-6296(90)90041-D.CrossRefPubMed
22.
Mulla H, Lawson G, von Anrep C, Burke MD, Upton DU, Firmin RK, Killer H: In vitro evaluation of sedative drug losses during extracorporeal membrane oxygenation. Perfusion. 2000, 15 (1): 21-26.CrossRefPubMed
23.
Roberts JA, Roberts MS, Semark A, Udy AA, Kirkpatrick CM, Paterson DL, Roberts MJ, Kruger P, Lipman J: Antibiotic dosing in the 'at risk' critically ill patient: linking pathophysiology with pharmacokinetics/pharmacodynamics in sepsis and trauma patients. BMC Anesthesiol. 2011, 11: 3-10.1186/1471-2253-11-3.CrossRefPubMedPubMedCentral
24.
Roberts JA, Joynt GM, Choi GY, Gomersall CD, Lipman J: How to optimise antimicrobial prescriptions in the intensive care unit: principles of individualised dosing using pharmacokinetics and pharmacodynamics. Int J Antimicrob Agents. 2012, 39 (3): 187-192. 10.1016/j.ijantimicag.2011.11.002.CrossRefPubMed
25.
Roberts JA: Using PK/PD to optimize antibiotic dosing for critically Ill patients. Curr Pharm Biotechnol. 2011, 12 (12): 2070-2079. 10.2174/138920111798808329.CrossRefPubMed
26.
Sessler CN, Gosnell MS, Grap MJ, Brophy GM, O'Neal PV, Keane KA, Tesoro EP, Elswick RK: The richmond agitation-sedation scale: validity and reliability in adult intensive care unit patients. Am J Respir Crit Care Med. 2002, 166 (10): 1338-1344. 10.1164/rccm.2107138.CrossRefPubMed
27.
Dasta JF, Kane SL, Gerlach AT, Cook CH: Bispectral index in the intensive care setting. Crit Care Med. 2003, 31 (3): 998-10.1097/01.CCM.0000055393.30990.1E. author reply 998–999CrossRefPubMed
28.
Ghassabian S, Moosavi SM, Valero YG, Shekar K, Fraser JF, Smith MT: High-throughput assay for simultaneous quantification of the plasma concentrations of morphine, fentanyl, midazolam and their major metabolites using automated SPE coupled to LC-MS/MS. J Chromatogr B Analyt Technol Biomed Life Sci. 2012, 903: 126-133.CrossRefPubMed
29.
Roberts JA, Kirkpatrick CM, Lipman J: Monte Carlo simulations: maximizing antibiotic pharmacokinetic data to optimize clinical practice for critically ill patients. J Antimicrob Chemother. 2011, 66 (2): 227-231. 10.1093/jac/dkq449.CrossRefPubMed
30.
Roberts JA, Field J, Visser A, Whitbread R, Tallot M, Lipman J, Kirkpatrick CM: Using population pharmacokinetics to determine gentamicin dosing during extended daily diafiltration in critically ill patients with acute kidney injury. Antimicrob Agents Chemother. 2010, 54 (9): 3635-3640. 10.1128/AAC.00222-10.CrossRefPubMedPubMedCentral
31.
Roberts JA, Kirkpatrick CM, Roberts MS, Robertson TA, Dalley AJ, Lipman J: Meropenem dosing in critically ill patients with sepsis and without renal dysfunction: intermittent bolus versus continuous administration? Monte carlo dosing simulations and subcutaneous tissue distribution. J Antimicrob Chemother. 2009, 64 (1): 142-150. 10.1093/jac/dkp139.CrossRefPubMed
32.
Roberts JA, Kirkpatrick CM, Roberts MS, Dalley AJ, Lipman J: First-dose and steady-state population pharmacokinetics and pharmacodynamics of piperacillin by continuous or intermittent dosing in critically ill patients with sepsis. Int J Antimicrob Agents. 2010, 35 (2): 156-163. 10.1016/j.ijantimicag.2009.10.008.CrossRefPubMed
33.
Roberts JA: Relevance of pharmacokinetics to antibiotic dosing in critically ill patients. Curr Pharm Biotechnol. 2011, 12 (12): 1981-1982. 10.2174/138920111798808310.CrossRefPubMed
34.
Roberts JA, Lipman J: Pharmacokinetic issues for antibiotics in the critically ill patient. Crit Care Med. 2009, 37 (3): 840-851. 10.1097/CCM.0b013e3181961bff. quiz 859CrossRefPubMed
35.
Shekar K, Roberts JA, Ghassabian S, Mullany DV, Wallis SC, Smith MT, Fraser JF: Altered antibiotic pharmacokinetics during extracorporeal membrane oxygenation: cause for concern?. J Antimicrob Chemother. 2012, Oct 30. [Epub ahead of print]
36.
Shekar K, Fung YL, Diab S, Mullany DV, McDonald CI, Dunster KR, Fisquet S, Platts DG, Stewart D, Wallis SC, et al: Development of simulated and ovine models of extracorporeal life support to improve understanding of circuit-host interactions. Crit Care Resusc. 2012, 14 (2): 105-111.PubMed
37.
Patel SB, Kress JP: Sedation and analgesia in the mechanically ventilated patient. Am J Respir Crit Care Med. 2012, 185 (5): 486-497. 10.1164/rccm.201102-0273CI.CrossRefPubMed
38.
39.
Kollef MH: Inadequate antimicrobial treatment: an important determinant of outcome for hospitalized patients. Clin Infect Dis. 2000, 31 (Suppl 4): S131-CrossRefPubMed
Metadata
Title
ASAP ECMO: Antibiotic, Sedative and Analgesic Pharmacokinetics during Extracorporeal Membrane Oxygenation: a multi-centre study to optimise drug therapy during ECMO
Authors
Kiran Shekar
Jason A Roberts
Susan Welch
Hergen Buscher
Sam Rudham
Fay Burrows
Sussan Ghassabian
Steven C Wallis
Bianca Levkovich
Vin Pellegrino
Shay McGuinness
Rachael Parke
Eileen Gilder
Adrian G Barnett
James Walsham
Daniel V Mullany
Yoke L Fung
Maree T Smith
John F Fraser
Publication date
01-12-2012
Publisher
BioMed Central
Published in
BMC Anesthesiology / Issue 1/2012
Electronic ISSN: 1471-2253
DOI
https://doi.org/10.1186/1471-2253-12-29

Other articles of this Issue 1/2012

BMC Anesthesiology 1/2012 Go to the issue

Research article

Increased NMDA receptor inhibition at an increased Sevoflurane MAC

Case report

Pulseless electrical activity during electroconvulsive therapy: a case report

Research article

A systematic review of the role of videolaryngoscopy in successful orotracheal intubation

Research article

Does using a femoral nerve block for total knee replacement decrease postoperative delirium?

Research article

Theoretical effect of hyperventilation on speed of recovery and risk of rehypnotization following recovery - a GasMan®simulation

Research article

Hospital staff education on severe sepsis/septic shock and hospital mortality: an original hypothesis