Frequently asked questions

Hear you can find answers to frequently asked questions regarding everything from randomization to follow-up.

Screening and randomization
Can we follow the recruitment status at all sites in STEPCARE?

Yes, visit stepcaretrial.com to see the recruitment status at all sites.

What is classified as OHCA vs IHCA?

OHCA: Arrest at the ER prior to final report from paramedics, non-admitted patients/relatives/care-givers whom have a cardiac arrest at the hospital or at a doctor’s appointment, patients with repeated cardiac arrests and non-sustained ROSC (<20 min) from the first OHCA at the arrival to the ER (continued events).

IHCA: Admitted patients to the hospital who have a cardiac arrest while at the hospital.

A patient has an unwitnessed cardiac arrest and the time of cardiac arrest is unknown. What time and date should I put in the eCRF?

If the exact time of the cardiac arrest is unknown then use the time of call to the dispatch center. This time is recorded, it is accurate and included in the EMS forms.

A patient is randomized in the emergency department but on the way to the ICU has a CT brain examination performed revealing a subarachnoid hemorrhage. Should this patient be excluded from the study?

Based on the intention to treat principle, data should be collected for this patient. However, the treatment goals for MAP, sedation and temperature will be up to the treating clinician. In these cases it may be an option to slightly delay the randomization until the performance of the CT brain, if there is a clear suspicion of an intracranial hemorrhage.   

The patient has had an OHCA and is scoring a GCS of 13 after the event. The patient is intubated to facilitate angiography and the patient arrives in the ICU intubated. Can this patient be enrolled?

No, if the GCS was high and the patient clearly obeyed commands after the OHCA then the patient should not be enrolled into STEPCARE. It is unlikely for the patient to be completely conscious after the arrest and then develop severe hypoxic brain injury.

A patient was initially awake and responding to commands after an out-of-hospital cardiac arrest. Upon arrival to hospital the patient deteriorated (new arrest, shock, pulmonary oedema), and was intubated and taken to the ICU. Is the patient eligible?

No the patient is not eligible and should be screened out using the criteria “Unconscious - NO”. This is because the reduced level of consciousness occurred due to a different event than the original OHCA

A patient was enrolled to the study but shortly after the randomisation it was decided that he was not for ICU care therefore was ineligible for the study. He later died in the Emergency dept. How would you like us proceed, a protocol deviation?

This is actually not a PD since the screening/inclusion presumably was decided before it was decided to withhold ICU-care. This will happen now and then in a trial like this. It happened in TTM1 and 2 and if you scrutinize the K-M curves they are part of the initial “drop” in survival. So please capture as much data as possible and the patient will remain in the ITT population for all analyses.

However, in a trial like this when it is not urgent to start the interventions it is reasonable to give a few minutes of observation and also consideration before screening and inclusion. Some patients on the margin will distinguish themselves as ineligible within the first half hour or so. That said, it is a generalizable population we are looking for, so rather include than exclude. And information that emerges downstream from the decision to randomize will never be considered PDs.

If a patient is randomised in another department (ED, Angio, Cath Lab) does the intervention have to be applied immediately or can the interventions wait until the patient is admitted to ICU?

The aim is to start the interventions as soon as possible. If the interventions can be commenced where the patient was randomised such as Emergency  Department, Angio or Cath Lab, otherwise the interventions can wait  until the patient is admitted to ICU.

Temperature
What temperature goal settings for CRRT should be applied on patients randomized to standarded temperature management without device who develop fever?

For unconscious patient who develop core temperature > 37.8°C within 72 h of being randomized to standard temperature management without device and for other clinical indications (anuric, acidic, hyperkalaemic etc) requires continuous renal replacement therapy (CRRT), the temperature goal should be as for other non-cardiac arrest ICU-patients (commonly CRRT with extracorporeal temperature management aimed at normothermia). If there is a refractory fever despite CRRT the temperature goal is to the discretion of the physician.

Is cooling with ice packs allowed?

Yes, but this method of cooling should not be used routinely in place of a device.  Instead, ice packs should only be used if the body temperature is sufficiently high that it would be of clinical concern outside the context of post cardiac arrest care.

My patient, enrolled in minimal sedation and temperature management arm requiring a cooling device, is tolerating the cooling device poorly. How can I enhance tolerability of cooling by device?

Assess  if the patient is possibly/likely ready for extubation within 1-2 hours and if the treating clinician therefore wishes to maintain no/light sedation. If this is the case and the patient is not tolerating the cooling device, the use of the device can be halted. If extubation does not occur within 1-2 hours restart the device and administer the level of sedation required for comfort, assess RASS regularly but aim to avoid deep sedation. 

Sedation
Are pain medications interpreted as sedation?

No, pain should be treated as per routine practice and the patient can receive opioids if pain is adequately assessed and detected. Opiate infusions are OK if low doses are used and they are titrated to correspond to patient´s needs.

Are there any restrictions about the sedative that is used? Can inhalation anesthetics be used?

The sedative medication is according to clinical routine in each unit.

My patient is randomized to receive minimal sedation. What if I need to perform clinical interventions or transport the patient to radiology department?

Whenever possible the sedation should be kept minimal, but if clinically indicated, sedation can be increased temporarily.

My patient is randomized to minimal sedation, but with minimal sedation or with no sedation at all, he/she is deeply comatose. Should I interpret this as deep sedation and thus protocol violation?

No, this is perfectly acceptable and belongs to the nature of the condition.

My patient is randomized to receive minimal sedation. What if I need to perform clinical interventions or transport the patient to radiology department?

Whenever possible the sedation should be kept minimal, but if clinically indicated, sedation can be increased temporarily.

My patient is randomized to minimal sedation and has myoclonic seizures. Can I use higher doses of sedation to treat convulsions?

If the patient has seizures and other forms of antiepileptic treatments are ineffective drugs such as propofol and benzos can be used as per the treating clinician. This will be recorded in the eCRF.

My patient, enrolled in minimal sedation and temperature management arm requiring a cooling device, is tolerating the cooling device poorly. How can I enhance tolerability of cooling by device?

Assess  if the patient is possibly/likely ready for extubation within 1-2 hours and if the treating clinician therefore wishes to maintain no/light sedation. If this is the case and the patient is not tolerating the cooling device, the use of the device can be halted. If extubation does not occur within 1-2 hours restart the device and administer the level of sedation required for comfort, assess RASS regularly but aim to avoid deep sedation. 

What if the patient ends up needing to be heavily sedated but was randomised to the minimum sedation strategy?

Sedation can be used in the minimal sedation group if there is a clinical indication for it as defined in the study protocol. The reason for this must be documented- if there is no documentation or record this will be classed as a protocol deviation. The need for deep sedation should be reassessed every 4-6 hours and if possible the use of sedation should be minimized as soon as appropriate. 

My patient is randomized to deep sedation but requires high doses of propofol (>4mg/kg/hour) and propofol syndrome is clinically suspected. Should I withdraw the patient from the study?

This patient should not be withdrawn from the study. We suggest changing to another sedative.

My patient is randomized to deep sedation. Should sedation breaks still be allowed daily?

No, sedation is to be kept constantly deep until the end of the 36-hour period.

If a participant is enrolled into the deep sedation arm and is profoundly comatose without sedation, and their RASS is -4 to -5, is supplemental sedation required while their RASS is -4 to -5?

In general if the patient randomized to deep sedation continuous sedation should be started targeting a RASS of -4 to -5. Sedation holidays are not indicated before 36 hours from randomization. However if  a participant is enrolled into the deep sedation arm and is found to be profoundly comatose without sedation, and their RASS is -4 to -5, then supplemental  sedation is NOT required while their RASS is -4 to -5.  

MAP
My patient is randomized to deep sedation and high MAP. The high dose of sedative impairs the possibility to reach target MAP. Which intervention should be prioritized.

First check the volume status and cardiac function. When optimized, you may try another sedative medication. If the problem remains and the noradrenaline dose is at a very high level (approaching 1 microgram/kg/min) deemed unsafe by the treating clinician, the MAP target can be reduced at increments of 5mmHg.

When does the MAP intervention of targeting a MAP of 65 or 85 mmHg stop?

The MAP intervention stops when the patient is extubated or at 72 hours whichever occurs first. If the patient is extubated but then need to be reintubated before 72 hours then the allocated MAP target should be used. When the intervention stops the MAP target will be up to the treating clinician.  

 

If the clinician decides that the MAP target should be modified (a lower target because of poor cardiac function and a high vasopressor need) should this be kept same for the whole intervention period? 

If possible the MAP target should be reassessed every 4-6 hours and if the situarion allows (decreasing need of a vasopressor) then the allocated MAP target should be reintated. 

What is the highest possible noradrenaline dose that can be used to achieve the higher MAP target?

We do not know this for sure and it may vary between patients. In the COMACARE and NEUROPROTECT trial there were patients who received up to 1 microgram/kg/min in order to achieve the higher MAP. There was no clear indication that these patients had more severe side-effect or a worse outcome. Nonetheless if the noradrenaline dose is high the patients should be assessed on a case by case basis.   

What do we do if we can not achieve the higher MAP target?

Assess patient clinically and consider all correctable factors such as hypovolemia, systolic dysfunction etc. If clinically indicated, the MAP target can be decreased in increments of 5 mmHg. Document in medical notes the reason why MAP target can not be achieved-  if there is no documentation or record this will be classed as a protocol deviation. Reassess the MAP target every 4-6 hours and if possible, increase the MAP target. 

What do the current international Guidelines recommend as the minimally accepted MAP after cardiac arrest?

The ERC/ESICM Guidelines (https://pubmed.ncbi.nlm.nih.gov/33773827/) recommend targeting a MAP of higher than 65 mmHg. The American Heart Association and the Neurocritical Care Society target a MAP of higher than 80 mmHg (https://pubmed.ncbi.nlm.nih.gov/38040992/) unless the patient has invasive brain oxygen monitoring. Therefore there are currently no clear scientific consensus on how to manage these patients. 

What blood pressure should you use if the patient is receiving treatment with an intra-arterial balloon pump (IABP)?

With an IABP the patient will have a pulse wave created by the heart and the pulse wave related to the inflation and deflation of the balloon. The IABP device will calculate a MAP which is a mean of the both the patients own beat and the one created by the IABP device. For MAP CARE aim to target a mean MAP of > 65 mmHg in the low MAP group and a mean MAP of > 85 mmHg in the high MAP group.

What should be the MAP target if the patient is receiving treatment with an IMPELLA device?

Aim to maintain the MAP target according to the randomization group of either >65 mmHg or >85 mmHg.

Neuroprognostication
What if a clinician would like to prognosticate earlier than the protocol states?

Prognostication for hypoxic brain injury should proceed according ESICM/ERC Guidelines. Indeed the WLST should not be applied before 72 hours. In rare cases WLST can be considered due to other reasons (family request, identification of terminal disease) before 72 hours. However this should be seen as a protocol violation and this must be documented. If the patient develops "brain death" before 72 hours this should not be seen as WLST or a protocol violation.  

How should we perform neuroprognostication in situations where confounding factors, especially the effect of sedation, cannot be ruled out?

The current guidelines state that effects of lingering sedation should be excluded. Sites should always aim to evaluate patients level of consciousness without sedation. There may be few exceptions where this is not feasible such as ventilator related complications . If these patients fulfill several sedation-independent criteria for poor prognosis (e.g. very high serum NSE or extensive brain injury in CT or absent N20 SEP responses), we suggest making clinical decisions based on the multimodal approach. If you register such a patient in the eCRF, please record the hours from the last dose of sedative agent to prognostication and still tick the box for poor outcome likely.

In borderline cases or if there is uncertainty about sedation having a role in a highly malignant EEG-pattern, we strongly recommend to achieve a sedation break or consider changing to a sedative agent with short half-life (e.g remifentanil or dexmedetomidine).

It is very important that prognostication and WLST for neurological reasons should be performed after 72 h, even in patients who show several criteria of very poor neurological prognosis earlier than at 72 hours.

Protocol deviations
How do we report a protocol deviation?

Protocol violations are reported through the eCRF. 

A patient was enrolled to the study but shortly after the randomisation it was decided that he was not for ICU care therefore was ineligible for the study. He later died in the Emergency dept. How would you like us proceed, a protocol deviation?

This is actually not a PD since the screening/inclusion presumably was decided before it was decided to withhold ICU-care. This will happen now and then in a trial like this. It happened in TTM1 and 2 and if you scrutinize the K-M curves they are part of the initial “drop” in survival. So please capture as much data as possible and the patient will remain in the ITT population for all analyses.

However, in a trial like this when it is not urgent to start the interventions it is reasonable to give a few minutes of observation and also consideration before screening and inclusion. Some patients on the margin will distinguish themselves as ineligible within the first half hour or so. That said, it is a generalizable population we are looking for, so rather include than exclude. And information that emerges downstream from the decision to randomize will never be considered PDs.