Date: June 20th, 2017

Reference: Bernard et al. Induction of Therapeutic Hypothermia During Out-of-Hospital Cardiac Arrest Using a Rapid Infusion of Cold Saline
The RINSE Trial (Rapid Infusion of Cold Normal Saline). Circulation 2016.

Guest Skeptic: Jay Loosley is a Registered Nurse, and an Advanced Care Paramedic in London.  His background includes working as a Research Assistant with the Ottawa Hospital Research Institute, Professor at Fanshawe College and currently, Superintendent of Education for Middlesex-London EMS, in London, Ontario, Canada.

Case:  A 71-year-old woman has a witnessed arrest while watching her granddaughter’s soccer game. By-standard CPR is started and EMS is called. They arrive quickly and take over the resuscitation. She is not in a shockable rhythm. They continue CPR, get intravenous access, give a round of epinephrine and then wonder if they should start rapid cooling en-route to the hospital with some cold saline.

Background: Therapeutic hypothermia post cardiac arrest has received a great deal of attention since 2002. Two relatively small randomized control trials published in the NEJM showed that hypothermia post cardiac arrest resuscitation was neuroprotective (Bernard et al and The Hypothermia after Cardiac Arrest Study Group).

The Cochrane Collaboration updated their review on hypothermia for neuroprotection in adults after CPR in 2012. They concluded:

  • “Conventional cooling methods to induce mild therapeutic hypothermia seem to improve survival and neurologic outcome after cardiac arrest. Our review supports the current best medical practice as recommended by the International Resuscitation Guidelines.” 

The SGEM was skeptical of prehospital cooling for OHCA after reviewing two studies on the subject (SGEM#21 and SGEM#54). Both papers showed no patient oriented benefit to pre-hospital cooling in patients with OHCA and return of spontaneous circulation (ROSC).

Then came the Targeted Temperature Management (TTM) Trial (Nielsen et al NEJM 2013). The bottom line was the TTM trial did not demonstrate a benefit of a targeted temperature of 33C vs. 36C for survival of OHCA (SGEM#82).

Clinical Question: Does rapid cooling by EMS with large volumes of 4C normal saline improve outcome in patients with OHCA receiving CPR?

Reference: Bernard et al. Induction of Therapeutic Hypothermia During Out-of-Hospital Cardiac Arrest Using a Rapid Infusion of Cold Saline
The RINSE Trial (Rapid Infusion of Cold Normal Saline). Circulation 2016.

  • Population: Adults with OHCA that resuscitation was started, had IV access and were still in cardiac arrest after initial resuscitation efforts.
    • Excluded: OCHA due to trauma, suspected intracranial bleed, known or suspected pregnancy, already cool (<34.5C) or patients with DNR.
  • Intervention: Rapid infusion of 30ml/kg IV cold saline (maximum two litres). Infusion was stopped if temperature reached 33C or pulmonary edema suspected.
  • Comparison: Standard care for OHCA
  • Outcome:
    • Primary Outcome: Survival to hospital discharge
    • Secondary Outcomes: Patients with shockable and non-shockable rhythm’s with ROSC, temperature in ROSC patients when arrived at hospital, and place of discharge (home, rehabilitation facility, nursing home or deceased at hospital discharge).

Authors’ Conclusions: In adults with out-of-hospital cardiac arrest, induction of mild therapeutic hypothermia using a rapid infusion of large-volume, intravenous cold saline during CPR may decrease the rate of return of a spontaneous circulation in patients with an initial shockable rhythm and produced no trend toward improved outcomes at hospital discharge.”

checklistQuality Checklist for Randomized Clinical Trials:

  1. The study population included or focused on those in the ED. No
  2. The patients were adequately randomized. They used a computer- generated random treatment allocation. Yes
  3. The randomization process was concealed. Yes
  4. The patients were analyzed in the groups to which they were randomized. Yes
  5. The study patients were recruited consecutively (i.e. no selection bias). Unsure
  6. The patients in both groups were similar with respect to prognostic factors. Yes
  7. All participants (patients, clinicians, outcome assessors) were unaware of group allocation. No
  8. All groups were treated equally except for the intervention. Yes
  9. Follow-up was complete (i.e. at least 80% for both groups). Yes
  10. All patient-important outcomes were considered. Yes
  11. The treatment effect was large enough and precise enough to be clinically significant. No

Key Results: A CONSORT (Consolidated Standards of Reporting Trials) flow diagram shows that 22,775 patients in cardiac arrest seen by EMS were screened. About half of those patients (11,476) in cardiac arrest had resuscitation commenced. Just over 10% (1,324) were enrolled in the study. A few more were excluded (122) and four withdrew leaving a final number for analysis of 1,198 patients (618 allocated to cooling and 580 allocated to standard care).

The included population had a mean age of about 65 years, almost ¾ being male, about 60% were witnessed bystander arrest, close to ½ were found in a ventricular fibrillation/tachycardia rhythm, 1/3 were asystole and 20% were pulseless electric activity.

No Difference in Survival to Hospital Discharge

  • Primary Outcome: Survival to hospital discharge – 10.2% cooling vs. 11.4% standard care (p=0.51)
  • Secondary Outcomes:
    • Patients with shockable rhythm who got ROSC at scene – 2% cooling vs. 50.6% standard care (p=0.031)
    • Non-shockable rhythm’s with ROSC at scene – 6% cooling vs. 29.4% standard care (p=0.43)
    • Temperature in ROSC patients when arrived at hospital 34.7C cooling vs. 35.4C standard care (p=<0.001)

RINSE secondary outcomes

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  1. Included Patients – It is important to remember that only 5% of all cardiac arrest patient seen by EMS were included in this study. This is because ½ of patients did not have resuscitation commenced and only about 10% of those patients were ultimately enrolled in the study. Another issue is that they included patients with non-shockable rhythms, which traditionally have dismal outcomes (2%) anyways.
  1. Lack of Blinding – Not everyone was blinded in this study. The outcome assessors were blinded to treatment allocation. It is not mentioned if the patients who survived found out which group they were allocated. The paramedics and hospital staff were aware of treatment allocation. This lack of blinding for the providers may or may not have introduced some bias. However, based on the hypothesis the bias should have been in the direction of the intervention.
  1. Temperature Decrease– The two groups started at a similar temperature (35.9C vs. 35.8C). However, the mean 1.2 litre of cold saline rapidly infused in the treatment group only decreased the temperature by 1.2C. When compared to the standard group there was only a 0.7C difference between the two groups (34.7C vs. 35.4C). While this was statistically significant it did not result in a change in the primary outcome (survival to hospital discharge). It could be that the decrease in temperature was not great enough or that decreasing the temperature does not make a patient oriented outcome difference.
  1. Stopped Early – The trial was designed for sample size of 2,512 patients. The study was stopped at approximately 50% of enrolment prior to the first planned interim analysis. This was due to the publication of the TTM trial. A number of the hospitals involved in the RINSE trial changed their target temperature as a result of that NEJM publication. Stopping trials early (usually for benefit) has a number of problems that have been discussed before on the SGEM. The problem of stopping this trial early is the precision of the results. This decrease in precision can be incorporated into any results from a systematic review and meta-analysis on therapeutic hypothermia. Ultimately, stopping the trial early biases the results and limits us from getting closer to the truth.
  1. Patient Oriented Outcome– The primary outcome in this study was survival to discharge. We are always saying a better patient oriented outcome would not just be survival but survival with good neurologic function. Their secondary outcome of place of discharge is a surrogate for good neurologic outcome. They found no statistical difference in what percentage of patients were discharged home (8.7% vs. 8.4% p=0.125). It would have been better if they had used a validated instrument for assessing neurologic outcome.

Comment on Authors’ Conclusion Compared to SGEM Conclusion: We agree with the authors’ conclusion.

SGEM Bottom Line: We do not have good evidence that providing pre-hospital cooling to patients with OHCA receiving CPR has a patient oriented benefit and therefore cannot be recommended at this time.

Case Resolution: The 71-year-old woman with the out-of-hospital cardiac arrest is not cooled in the field. You get ROSC, transport her to hospital and hope she survives to hospital discharge neurologically intact.

Jay Loosley

Jay Loosley

Clinical Application: This is another study reinforcing that cooling pre-hospital by EMS for OHCA should not be performed.

What do I tell my patient? I will tell the patient’s partner that her wife had a cardiac arrest. We were able to bring her back but she is still unconscious. The prognosis is poor but the emergency department staff will do what they can.

Keener Contest: Last weeks’ winner was Matthew Corey from Fountain Hills, Arizona. He knew that Bret Michaels from the band Poison suffered an atraumatic cerebral hemorrhage.

Listen to the episode on iTunes to here the question for this week.  If you know the answer then send an email to TheSGEM@gmail.com with “keener” in the subject line. The first correct answer will receive a cool skeptical prize.

FOAM logoOther FOAMed:

  • St. Emlyn’s JC – Pre-hospital therapeutic hypothermia: The RINSE trial.
  • EM Literature of Note – Not Seeing Any Value in RINSE
  • REBEM EM – Targeted Temperature Management in Out-of-Hospital Cardiac Arrest: 33°C or 36°C?


Remember to be skeptical of anything you learn, even if you heard it on the Skeptics’ Guide to Emergency Medicine.