Effects of neonatal extracorporeal membrane oxygenation circuits on drug disposition

Mulla, Hussain; Lawson, Graham; Woodland, E. D.; Peek, Giles J.; Killer, Hilliary; Firmin, Richard K.; Upton, David

doi:10.1016/s0011-393x(00)90010-9

Cited by 16 publications

(20 citation statements)

References 8 publications

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“…The concentrations between Ports B and C did not vary much for morphine, indicating minimal loss in the MO, but were quite different for lorazepam, suggestive of greater drug loss. The results of the present study are somewhat comparable to the results of lorazepam and morphine in the two studies by Mulla et al ., 8,9 which also assessed lorazepam and morphine disposition in that they both show significant drug loss to the ECMO circuit components, although the experimental conditions are quite different between our study and these studies. The old circuits (24-h circuits) in this study tended to absorb or adsorb more drug than the newer circuits.…”

Section: Discussionmentioning

confidence: 74%

Sedative clearance during extracorporeal membrane oxygenation

Bhatt‐Mehta

Annich

2005

Perfusion

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The effects of polyvinyl chloride (PVC) tubing and membrane oxygenator (MO) on the concentrations of lorazepam and morphine in the neonatal extracorporeal membrane oxygenation (ECMO) circuit were evaluated using an in vitro model that included a closed ECMO circuit with a MO, heat exchanger, bladder and PVC tubing. The circuit was primed with blood, electrolytes, albumin and heparin and maintained at physiologic pH and temperature throughout by frequent measurement of blood gas pH and a temperature probe. Lorazepam and morphine were each studied separately in three separate, but identical circuits for 6 h on the day of circuit prime (new circuit) and then again for 6 h at 24 h (old circuit). Each circuit (new and old) was spiked once with lorazepam to a final concentration of 250 ng/mL or with morphine to a final concentration of 70 ng/mL in the circuit. Serial samples were drawn at baseline and every 30-60 min for 6 h at the site of injection and pre- and post-MO for each circuit. Lorazepam and morphine concentrations were analysed using gas chromatography with electron capture and gas chromatography with mass spectrometry, respectively. The concentrations of morphine and lorazepam at various sample sites and time points were expressed as a percentage of the original concentration. This single-dose study shows that up to 50% of a dose of lorazepam and 40% of a dose of morphine may be extracted by PVC and MO during bypass, depending on the age of the circuit. As the circuits become older, this amount could increase. These data may explain, in part, the higher doses of lorazepam and morphine required to sedate patients during ECMO.

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Section: Discussionmentioning

confidence: 74%

Sedative clearance during extracorporeal membrane oxygenation

Bhatt‐Mehta

Annich

2005

Perfusion

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“…Administration of large dosages of narcotics and sedatives has become routinely necessary in ECMO patients, especially in patients requiring prolonged extracorporeal support. 1 In particular, pediatric patients are the most difficult age group of ECMO patients in which to achieve and maintain adequate pain and anxiety control with pharmacotherapeutic agents. This is largely due to difficulty in accurate assessment of pain and anxiety control as well as the narrow margin of error for side effects associated with use of these medications.…”

Section: Introductionmentioning

confidence: 99%

A survey for pain and sedation medications in pediatric patients during extracorporeal membrane oxygenation

et al. 2005

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Routine administration of large amounts of pain and sedative medication is common to critically ill pediatric patients undergoing extracorporeal membrane oxygenation (ECMO) for cardiopulmonary failure. It has been our experience that pediatric patients are the most difficult age group in which to achieve an ideal pain and sedative control due to the narrow margin of safety. The purpose of this study was to determine the general practice guideline used for pain and anxiolytic pharmacotherapy for pediatric patients at ECMO centers. We sent a survey questionnaire to all ECMO centers in the USA that treat pediatric respiratory failure patients. Of the 46 responding centers (including telephone follow-ups), 37 (80%) centers had an active pediatric ECMO programs for patients with severe respiratory failure. Fentanyl was the most commonly used pain medication and continuous infusion, administered directly to the patient, was preferred. Subjective effectiveness of various pharmacological agents was variable without clear consensus; however, midazolam was considered to be the most effective agent used.

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“…10 Polymethylpentene fiber oxygenator system (permanent life support system), a hydrophobic material used in our ECMO circuit, is known to be associated with significant drug loss. 5,11,12 This is possibly explained by preferential migration of hydrophobic drugs into the circuit. Rifampicin is a highly lipid-soluble drug and may be significantly sequestered, thereby causing underexposure of antituberculosis agents in the patient.…”

Section: Discussionmentioning

confidence: 99%

Insufficient Serum Levels of Antituberculosis Agents During Venovenous Extracorporeal Membrane Oxygenation Therapy for Acute Respiratory Distress Syndrome in a Patient with Miliary Tuberculosis

2014

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Prolonged cardiopulmonary support via extracorporeal membrane oxygenation (ECMO) is essential for patients with life-threatening respiratory or cardiac failure. Extracorporeal membrane oxygenation is known to be associated with conditions that potentially alter the distribution and elimination properties of drugs. However, little has been documented concerning pharmacokinetic changes of antibacterial agents in critically ill patients under oxygenation conditions. We describe a case of miliary tuberculosis with acute respiratory distress syndrome supported by venovenous ECMO. The patient had persistently positive acid-fast bacilli smears for respiratory specimens. Accordingly, standard doses of antituberculosis agents, including isoniazid, rifampicin, ethambutol, and pyrazinamide, were administered with appropriate therapeutic drug monitoring. Drug levels were found to be subtherapeutic. Therapeutic target levels were achieved after altering the route of administration and making dosage adjustments. Although this is a single case report, our observations indicate the need for therapeutic drug monitoring to achieve appropriate target concentrations for antituberculosis agents in patients with miliary tuberculosis under ECMO.

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Effects of neonatal extracorporeal membrane oxygenation circuits on drug disposition

Cited by 16 publications

References 8 publications

Sedative clearance during extracorporeal membrane oxygenation

Sedative clearance during extracorporeal membrane oxygenation

A survey for pain and sedation medications in pediatric patients during extracorporeal membrane oxygenation

Insufficient Serum Levels of Antituberculosis Agents During Venovenous Extracorporeal Membrane Oxygenation Therapy for Acute Respiratory Distress Syndrome in a Patient with Miliary Tuberculosis

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