Clinical trial NCT02033733: When Cooling a Patient After Cardiac Arrest, Does Use of a Neuromuscular Blocking Agent Make Your Job Easier?
Official title: Post-arrest Therapeutic Hypothermia. Does Use of Neuromuscular Blockers Achieve Faster Cooling Time?
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Postcardiac Arrest Therapeutic Hypothermia
Keywords: Post cardiac arrest
Postcardiac arrest therapeutic hypothermia
Therapeutic hypothermia protocol
Neuromuscular blocking agents
Muscle relaxants
Hypothermia-induced increased muscle tone
Microshivering
Lead sponsor: London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's
Sponsor class: OTHER
Collaborators: name: University of Western Ontario, Canada
First posted: 2014-01-13
Enrollment: 400
Sex: ALL
Minimum age (years): 18
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: RETROSPECTIVE
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.

Brief summary: 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.

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 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.

Primary outcomes:
measure: Time to attaining target temperature (hours).
timeFrame: From initiation of hypothermia protocol to reaching a core body temperature of ≤34ºC, assessed up to 72 hours from protocol initiation.
Secondary outcomes:
measure: Cerebral performance category score on hospital discharge.
timeFrame: Upon discharge from hospital, assessed up to 36 months postcardiac arrest.
measure: Hospital length of stay postcardiac arrest (days).
timeFrame: Days spent in hospital after successful resuscitation from cardiac arrest, assessed up to 36 months from the date of cardiac arrest
measure: Intensive care unit length of stay postcardiac arrest (days).
timeFrame: Days spent in the intensive care unit after successful resuscitation from cardiac arrest, assessed up to 36 months from the date of cardiac arrest.
Other outcomes:
measure: Time required to normalize lactate (hours)
timeFrame: Time from a sustained return of spontaneous circulation to the first recorded normal lactate level, assessed up to 7 days (168 hours) postcardiac arrest.
Locations:
city: London
country: Canada
facility: University Hospital, London Health Sciences Centre, University of Western Ontario
state: Ontario
city: London
country: Canada
facility: Victoria Hospital, London Health Sciences Centre, University of Western Ontario
state: Ontario
Study officials:
affiliation: Western University, Canada
name: Eyad Althenayan, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Western University, Canada
name: Philip Jones, MD, FRCPC
role: STUDY_DIRECTOR
affiliation: Western University, Canada
name: Bryan Young, MD, FRCPC
role: STUDY_CHAIR
affiliation: Western University, Canada
name: Ahmed F Hegazy, MD, FRCPC
role: STUDY_DIRECTOR
affiliation: Western University, Canada
name: Ana Igric, MD, FRCSC
role: STUDY_DIRECTOR
affiliation: Western University, Canada
name: Carolyn Benson, MD
role: STUDY_DIRECTOR
References:
citation: Sendelbach S, Hearst MO, Johnson PJ, Unger BT, Mooney MR. Effects of variation in temperature management on cerebral performance category scores in patients who received therapeutic hypothermia post cardiac arrest. Resuscitation. 2012 Jul;83(7):829-34. doi: 10.1016/j.resuscitation.2011.12.026. Epub 2012 Jan 8.
citation: Werlhof V, Sessler DI. Pancuronium does not decrease oxygen consumption during hypothermic or normothermic cardiopulmonary bypass. Anesth Analg. 1995 Sep;81(3):465-8. doi: 10.1097/00000539-199509000-00006.
citation: Peberdy MA, Callaway CW, Neumar RW, Geocadin RG, Zimmerman JL, Donnino M, Gabrielli A, Silvers SM, Zaritsky AL, Merchant R, Vanden Hoek TL, Kronick SL; American Heart Association. Part 9: post-cardiac arrest care: 2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation. 2010 Nov 2;122(18 Suppl 3):S768-86. doi: 10.1161/CIRCULATIONAHA.110.971002.