When Cooling a Patient After Cardiac Arrest, Does Use of a Neuromuscular Blocking Agent Make Your Job Easier?

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified January 2014 by Lawson Health Research Institute
Sponsor:
Collaborator:
University of Western Ontario, Canada
Information provided by (Responsible Party):
Eyad AlThenayan, University of Western Ontario, Canada
ClinicalTrials.gov Identifier:
NCT02033733
First received: January 4, 2014
Last updated: January 9, 2014
Last verified: January 2014
  Purpose

After successful resuscitation from cardiac arrest, cooling the whole body is a well established treatment that improves the chances of the brain recovering. This however, has to be done within a certain time-frame from the arrest. The purpose of this study is to explore the best way of dosing the muscle relaxing medications that are given during the cooling process.

Hypothesis: In the context of our institutional therapeutic hypothermia protocol, cisatracurium infusions lead to faster drops in core temperature when compared to cisatracurium prn boluses alone.


Condition Intervention
Postcardiac Arrest Therapeutic Hypothermia
Drug: Cisatracurium infusion
Drug: Cisatracurium prn bolus

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Retrospective
Official Title: Post-arrest Therapeutic Hypothermia. Does Use of Neuromuscular Blockers Achieve Faster Cooling Time?

Resource links provided by NLM:


Further study details as provided by Lawson Health Research Institute:

Primary Outcome Measures:
  • Time to attaining target temperature (hours). [ Time Frame: From initiation of hypothermia protocol to reaching a core body temperature of ≤34ºC, assessed up to 72 hours from protocol initiation. ] [ Designated as safety issue: No ]

    The primary outcome will be a binary outcome that is: adequate cooling time versus inadequate cooling time based on the time needed to achieve target temperatures. We will define adequate cooling time as being ≤ 4 hours from initiation of protocol to reaching target temperature. Inadequate cooling time will be requiring > 4 hours to achieve that goal. Target core body temperature range in our institutional protocol is 32 - 34ºC.

    The primary outcome will be assessed using a logistic regression model, constructed using covariates affecting speed of cooling as determined by expert opinion and current evidence apriori. The variables will be age, sex, weight, pre-protocol core body temperature, initial arrest rhythm and infusion versus boluses. The model will be used to determine whether the cisatracurium dosing regimen is an independent predictor of adequate patient cooling time or not.



Secondary Outcome Measures:
  • Cerebral performance category score on hospital discharge. [ Time Frame: Upon discharge from hospital, assessed up to 36 months postcardiac arrest. ] [ Designated as safety issue: No ]

    Neurological outcome on discharge from hospital as defined by the cerebral performance category (CPC) scale. The CPC scale is a 5 point scale. The outcome measure will be dichotomized into good or bad. Good outcome will be equivalent to CPC scores of 1 & 2 (where the patient is independent), and bad outcome will be equivalent to CPC scores of 3, 4 & 5 (where the patient is either dependent or dead). We will examine whether the use of a neuromuscular blocking agent infusion correlates with good CPC scores on hospital discharge or not.

    CPC Scale:

    1. Functioning normally and independent, possibly with a minor disability.
    2. Moderately disabled, still independent.
    3. Conscious but with a severe disability, dependent.
    4. Unconscious (comatose or in a persistent vegetative state).
    5. Brain dead or dead by traditional criteria.

  • Hospital length of stay postcardiac arrest (days). [ Time Frame: Days spent in hospital after successful resuscitation from cardiac arrest, assessed up to 36 months from the date of cardiac arrest ] [ Designated as safety issue: No ]
    Hospital length of stay (LOS) post-cardiac arrest will be calculated from the day of the cardiac arrest to the day of hospital discharge. If prior to the arrest the patient was an inpatient, we will only count the days from the arrest to discharge. Days spent in hospital prior to the arrest will not be included.

  • Intensive care unit length of stay postcardiac arrest (days). [ Time Frame: Days spent in the intensive care unit after successful resuscitation from cardiac arrest, assessed up to 36 months from the date of cardiac arrest. ] [ Designated as safety issue: No ]
    The length of stay (LOS) in the intensive care unit (ICU) after successful resuscitation from cardiac arrest in days.


Other Outcome Measures:
  • Time required to normalize lactate (hours) [ Time Frame: Time from a sustained return of spontaneous circulation to the first recorded normal lactate level, assessed up to 7 days (168 hours) postcardiac arrest. ] [ Designated as safety issue: No ]
    Neuromuscular blocking agent (NMBA) infusions are likely to abolish microshivering and hence reduce lactate generation. This is likely to reduce the times needed for patients to normalize their lactate levels post resuscitation from cardiac arrest. We will examine whether NMBA infusions were associated with better lactate clearance rates (shorter times to normalization of lactate levels) in comparison to NMBA prn boluses or not.


Estimated Enrollment: 400
Study Start Date: January 2014
Estimated Study Completion Date: February 2015
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
Adequate cooling time
Patients that reached target temperature within 4 hours of initiation of the hypothermia protocol will be in the "adequate cooling time" group.
Drug: Cisatracurium infusion

This group will include postcardiac arrest patients that have received a cisatracurium infusion as part of their therapeutic hypothermia protocol. It will only include patients that had their infusion started within 2 hours from protocol initiation. Patients that received an infusion as a rescue measure (beyond the first 2 hours) or did not receive and infusion at all will not be included in this group.

Most patients admitted to our ICU postcardiac arrest prior to October 2011, will likely belong to this group (the cisatracurium infusion group).

Other Names:
  • Neuromuscular blocking agent infusion
  • NMBA infusion
  • Continuous NMBA infusion
  • Continuous cisatracurium infusion
  • Cisatracurium by continuous infusion
Drug: Cisatracurium prn bolus
Patients that have not received a cisatracurium infusion within the first 2 hours from protocol initiation will be in this group. These are likely to be patients admitted to our ICU after October 2011 (when the protocol change happened).
Other Names:
  • neuromuscular blocking agent prn bolus
  • NMBA prn bolus
  • cisatracurium intermittent bolus
  • intermittent bolus administration of cisatracurium
Inadequate cooling time
Patients that did not reach target temperature within 4 hours of initiation of the hypothermia protocol will be in the "inadequate cooling time" group.
Drug: Cisatracurium infusion

This group will include postcardiac arrest patients that have received a cisatracurium infusion as part of their therapeutic hypothermia protocol. It will only include patients that had their infusion started within 2 hours from protocol initiation. Patients that received an infusion as a rescue measure (beyond the first 2 hours) or did not receive and infusion at all will not be included in this group.

Most patients admitted to our ICU postcardiac arrest prior to October 2011, will likely belong to this group (the cisatracurium infusion group).

Other Names:
  • Neuromuscular blocking agent infusion
  • NMBA infusion
  • Continuous NMBA infusion
  • Continuous cisatracurium infusion
  • Cisatracurium by continuous infusion
Drug: Cisatracurium prn bolus
Patients that have not received a cisatracurium infusion within the first 2 hours from protocol initiation will be in this group. These are likely to be patients admitted to our ICU after October 2011 (when the protocol change happened).
Other Names:
  • neuromuscular blocking agent prn bolus
  • NMBA prn bolus
  • cisatracurium intermittent bolus
  • intermittent bolus administration of cisatracurium

Detailed Description:

STUDY RATIONALE:

A large proportion of comatose survivors of cardiac arrest presenting to our intensive care units at London Health Sciences Centre (LHSC) undergo therapeutic hypothermia. Current evidence suggests that timely achievement of target temperatures is desirable to improve outcomes. At LHSC, this intervention is protocolized with a defined set of preprinted orders that includes a dosing regimen for neuromuscular blocking agents (NMBA's). Our preprinted protocol has been in place since January of 2004. Cisatracurium infusions were part of the therapeutic hypothermia protocol until October 2011. Since that time, our protocol has changed to cisatracurium prn boluses for any observed shivering. In this study we will examine if there has been any change in the times to achieving target temperatures with the implementation of this change. It is important to note that no other change in our protocol has taken place since it was first implemented, making our before and after comparison valid and fair.

Our hypothesis is that NMBA infusions lead to a faster drop in core temperatures when compared to NMBA prn boluses. If this were to stand true, we would expect cisatracurium IV infusions to result in faster reductions in core temperature when compared with cisatracurium prn boluses in the context of our therapeutic hypothermia protocol. Hypothermia has been known to cause a subclinical increase in muscle tone. This previously reported phenomenon has been named "microshivering". When attempting to reduce core temperatures, microshivering is likely a natural body response to try to restore body temperature back to normal. We therefore hypothesize that NMBA infusions are likely more effective at abolishing microshivering, which would be a desirable effect when trying to induce therapeutic hypothermia.

Although current American Heart Association (AHA) guidelines suggest considering the administration of NMBA's to facilitate induced hypothermia and control shivering. Their recommendation is to minimize the duration of NMBA use or if possible, avoid them altogether. After the publication of these guidelines our institutional protocol changed to prn boluses instead of the previous infusion orders. We therefore believe it is important to examine the effects of this change on our cooling protocol and potentially add to the growing body of knowledge in this field.

  Eligibility

Ages Eligible for Study:   18 Years to 90 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

All patients admitted to the intensive care unit (ICU) with a diagnosis of postcardiac arrest between Jan 2008 and Dec 2012 will be examined.

Criteria

Inclusion Criteria:

  • Admission to adult ICU (age ≥18 years) at London Health Sciences Centre
  • Primary reason for ICU admission: postcardiac arrest
  • Both in-hospital and out-of-hospital cardiac arrest will be included
  • ICU admission between Jan 2008 and Dec 2012.

Exclusion Criteria:

- ICU admissions primarily for reasons other than cardiac arrest.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02033733

Contacts
Contact: Ahmed F Hegazy, MD, FRCPC 1(519) 860-4917 ahmed.hegazy@londonhospitals.ca
Contact: Eyad AlThenayan, MD Eyad.Althenayan@lhsc.on.ca

Locations
Canada, Ontario
University Hospital, London Health Sciences Centre, University of Western Ontario Not yet recruiting
London, Ontario, Canada, N6A 5A5
Contact: Ahmed F Hegazy, MD, FRCPC    1(519) 860-4917    ahmed.hegazy@londonhospitals.ca   
Contact: Eyad Althenayan, MD    1 (519) 685-8500 ext 19119    eyad.althenayan@lhsc.on.ca   
Sub-Investigator: Ahmed F Hegazy, MD, FRCPC         
Victoria Hospital, London Health Sciences Centre, University of Western Ontario Not yet recruiting
London, Ontario, Canada, N6A 5W9
Contact: Ahmed F Hegazy, MD, FRCPC    1(519) 860-4917    ahmed.hegazy@londonhospitals.ca   
Contact: Eyad Althenayan, MD    1 (519) 685-8500 ext 19119    eyad.althenayan@lhsc.on.ca   
Sub-Investigator: Ahmed F Hegazy, MD, FRCPC         
Sponsors and Collaborators
Lawson Health Research Institute
University of Western Ontario, Canada
Investigators
Principal Investigator: Eyad Althenayan, MD University of Western Ontario, Canada
Study Director: Philip Jones, MD, FRCPC University of Western Ontario, Canada
Study Chair: Bryan Young, MD, FRCPC University of Western Ontario, Canada
Study Director: Ahmed F Hegazy, MD, FRCPC University of Western Ontario, Canada
Study Director: Ana Igric, MD, FRCSC University of Western Ontario, Canada
Study Director: Carolyn Benson, MD University of Western Ontario, Canada
  More Information

Publications:
Responsible Party: Eyad AlThenayan, Dr. Eyad AlThenayan, University of Western Ontario, Canada
ClinicalTrials.gov Identifier: NCT02033733     History of Changes
Other Study ID Numbers: 5511
Study First Received: January 4, 2014
Last Updated: January 9, 2014
Health Authority: Canada: University of Western Ontario

Keywords provided by Lawson Health Research Institute:
Post cardiac arrest
Postcardiac arrest therapeutic hypothermia
Therapeutic hypothermia protocol
Neuromuscular blocking agents
Muscle relaxants
Hypothermia-induced increased muscle tone
Microshivering

Additional relevant MeSH terms:
Hypothermia
Heart Arrest
Heart Diseases
Cardiovascular Diseases
Body Temperature Changes
Signs and Symptoms
Cisatracurium
Atracurium
Neuromuscular Blocking Agents
Neuromuscular Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Neuromuscular Nondepolarizing Agents
Nicotinic Antagonists
Cholinergic Antagonists
Cholinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 18, 2014