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Pharmacokinetic Alterations During ECMO

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ClinicalTrials.gov Identifier: NCT01938079
Recruitment Status : Completed
First Posted : September 10, 2013
Results First Posted : September 29, 2016
Last Update Posted : September 29, 2016
Sponsor:
Information provided by (Responsible Party):
Daniel Brodie, Columbia University

Tracking Information
First Submitted Date  ICMJE September 5, 2013
First Posted Date  ICMJE September 10, 2013
Results First Submitted Date  ICMJE August 5, 2016
Results First Posted Date  ICMJE September 29, 2016
Last Update Posted Date September 29, 2016
Study Start Date  ICMJE September 2013
Actual Primary Completion Date February 2015   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 5, 2016)
Cumulative Fentanyl Equivalents From ECMO Initiation to Decision to Achieve Wakefulness [ Time Frame: Up to 14 days ]
Culmulative fentanyl equivalents meaning the combination of sedative drug regimen - measured in mg - from ECMO initiation to decision to achieve wakefulness.
Original Primary Outcome Measures  ICMJE
 (submitted: September 5, 2013)
A decrease in fentanyl or hydromorphone requirements with ketamine infusion. [ Time Frame: Up to 14 days ]
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Pharmacokinetic Alterations During ECMO
Official Title  ICMJE Pharmacokinetic Alterations During ECMO (Ketamine and Extracorporeal Membrane Oxygenation)
Brief Summary In a healthy patient, the lungs provide oxygen to the blood and remove carbon dioxide. However, in patients with severe lung failure, blood may not adequately be delivered to the lungs, or the lungs may not adequately supply blood with oxygen. In this case, patients may require assistance from a machine to help provide this oxygen. Extracorporeal membrane oxygenation (ECMO) is a device that acts as an artificial lung, allowing the patient to recover from their illness. Patients receiving support from ECMO are often put in a medically induced coma while their lungs heal. Certain drugs may stick to the internal surfaces of the machine; therefore leading to decreased concentrations. Patients receiving ECMO often require high doses of both pain medications and sedatives in order to provide comfort. Low doses of a drug, ketamine, may help to provide additive effects to pain relief and allow lower doses of other pain medications. The hypothesis is that patients treated with continuous intravenous ketamine, will have lower requirements of other pain medications while receiving ECMO for acute respiratory failure while achieving the desired level of sedation.
Detailed Description

The administration of analgesia and sedation is common practice for patients receiving mechanical ventilation with extracorporeal membrane oxygenation (ECMO). Maintaining patient comfort and safety, while not oversedating and thereby risking prolonged mechanical ventilation and delirium, is an ongoing balancing act which presents a daily challenge for Intensive Care Unit (ICU) clinicians. Medication selection should be based on the patient's needs with titration to a predetermined goal in accordance with published guidelines.

However, there are major pharmacokinetic changes that occur with the use of ECMO, including sequestration of medications within the circuit, increased volume of distribution, and in some cases decreased clearance. As a result patient's receiving ECMO often require very high doses of both analgesics and sedatives in order to provide comfort and ventilator synchrony. In patients not receiving ECMO, excess sedative exposure, especially with benzodiazepines, leads to increased mechanical ventilation time, prolonged ICU stay, short and long term neurocognitive impairments, and increased mortality. No studies address these outcomes in patients receiving ECMO.

Ketamine, a non-barbiturate phencyclidine derivative, provides analgesia with relative hemodynamic stability and maintained airway reflexes. However, its popularity waned because of an undesirable side effect profile: Hallucinations, delirium, lacrimation, tachycardia, and potential for an increase in intracranial pressure (ICP) and coronary ischemia. Recent research, however, suggests that low doses of ketamine infusions in combination with opiates may not be associated with adverse sequelae and may improve outcomes in the critically ill population. To date, there are no studies that have compared clinical outcomes in ICU patients sedated with ketamine as compared with other sedative agents.

Supplemental sedation with intravenous ketamine infusion may decrease opioid and sedative requirements for patients receiving mechanical ventilation and ECMO. The benefits of decreased opioid and sedative requirements may translate to fewer gastrointestinal side effects, decreased withdrawal syndromes, and a reduced rate of delirium.

Deep levels of sedation are often required at the commencement of ECMO for acute respiratory failure, which correlates to a Richmond Agitation Sedation Score (RASS) of -5. Supplemental low doses of ketamine infusions may help the prescriber achieve this goal without having to use very high doses of fentanyl or hydromorphone and midazolam.

Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Condition  ICMJE Acute Respiratory Failure
Intervention  ICMJE
  • Drug: Ketamine
    Ketamine will be initiated as a one-time 40 mg bolus of ketamine followed by a continuous intravenous infusion of 5 micrograms/kg/min at the start of ECMO.
    Other Name: Ketalar
  • Other: Sedative drug regimen
    (Standard of Care) Fentanyl or hydromorphone and midazolam infusions will be administered to all patients and titrated at the discretion of the attending physician to maintain the desired level of sedation.
Study Arms  ICMJE
  • Active Comparator: Sedative without Ketamine
    Subjects will receive sedative drug regimen without Ketamine.
    Intervention: Other: Sedative drug regimen
  • Experimental: Sedative with Ketamine
    Subjects will receive sedative drug regimen with Ketamine.
    Interventions:
    • Drug: Ketamine
    • Other: Sedative drug regimen
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: September 5, 2013)
20
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE August 2015
Actual Primary Completion Date February 2015   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Receiving ECMO for acute respiratory failure
  • Requiring deep sedation (RASS -5)

Exclusion Criteria:

  • Allergy to ketamine
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 90 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01938079
Other Study ID Numbers  ICMJE AAAM0950
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Daniel Brodie, Columbia University
Study Sponsor  ICMJE Columbia University
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Daniel Brodie, MD Columbia University
PRS Account Columbia University
Verification Date August 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP