CAT ReviewTherapeutic hypothermia for neuroprotection in adults after cardiopulmonary resuscitation

Rosie MacfadyenSpR

Intensive Care Unit, Royal Infirmary of Edinburgh

Citation

• Arrich J, Holzer M, Herkner H, Mullner M. Hypothermia for neuroprotection in adults after cardiopulmonary resuscitation. Cochrane Database of Systematic Reviews 2009, Issue 4 Art no.: CD004128

Three part clinical question

• Patients: – Adult patients who have suffered cardiac arrest – > 18y, in or out of hospital

• Intervention:– Mild therapeutic hypothermia – <35°C, regardless of method of T° reduction, applied

within 6h of arrival at hospital• Outcome:– Neurological recovery – best neurologic outcome

during hospital stay.

The rationale

• Prevention of postresuscitation syndrome– ↑ CPP – restores energy stores to neurons– But also triggers harmful chemical cascades - ↑

reactive oxygen species, catecholamines, glutamate, dopamine.

– BBB disruption– Multifocal damage to brain.

The rationale

• Aims to preserve neurological function in pts comatose post cardiac arrest

• TH may influence several damaging pathways simultaneously, in addition to ↓ CMRO2

• Inhibition of catecholamine/dopamine/free radical release.

• Preservation of BBB• Preservation of cerebral microcirculation• Preservation ATP stores

Primary Outcome

• Neurological recovery – best neurological outcome during hospital stay.

• Graded as ‘good’ if Cerebral Performance Category 1-2

• Secondary outcomes– Survival to hospital discharge– Survival at 6 months– Long-term dependency– Cost effectiveness

• Examination of adverse events

Measure of effect

• Relative risk of achieving good neurological recovery in patients allocated to hypothermia compared to those not receiving hypothermia at hospital discharge

Study selection

• Limited to randomised and ‘quasi-randomised’ trials on adult patients remaining comatose after cardiac arrest.

• 5 trials met criteria – 481 patients in total– HACA NEJM 2002 ‘the European one’- 275 pts– Bernard NEJM 2002 ‘the Australian one’ – 77 pts– Hachimi-Idrissi Resuscitation 2001 – 33 pts– Laurent J Am Coll Cardiol 2005 – 42 pts– Mori Crit Care Med 2000 - 54

Clinical heterogeneity

• 3/5 trials ‘conventional cooling methods’• Duration of cooling variable; 3-72h• Laurent – high-volume haemofiltration

200ml/kg/hr• Mori – unclear cooling method

• These two study analysed separately – effect not pooled with other studies.

Risk of Bias

• Mode of randomization, allocation concealment– 3/5 adequate – HACA, Hachimi-idrissi, Laurent

• Level of blinding at follow-up– 3/5 adequate – Bernard, HACA, Hachimi-Idrissi

• Loss to follow-up– HACA – lost 2/275 patients

• Comparability of groups– HACA – some baseline differences between groups – adjusted for.– Bernard – differences in sex/rate of bystander CPR between groups – not

adjusted for– Mori- no information on baseline characteristics of patient groups

Neurological outcome: cooling vs no cooling

Survival to discharge: cooling vs no cooling

Secondary outcomes

• Survival at 6 months and long-term – No data on this outcome

• Quality of life and long-term dependency– No data on this outcome

• Cost effectiveness – No data on this outcome

Subgroup analyses

• Likely to benefit– OOHCA – 4/5 looked only at OOHCA– Presumed cardiac aetiology– VF/VT

• Unable to ascertain benefit– In hospital cardiac arrest– Asystole as presenting rhythm– Non-cardiac causes of arrest

Adverse events

• No statistically significant differences in events in cooled vs non-cooled– Bleeding– Pneumonia– Sepsis– Pancreatitis– Renal failure/need for RRT– Pulmonary oedema– Seizures– Lethal arrhythmias– Hypocalcaemia/hypophosphataemia

12 EBM Questions

• Do the methods allow accurate testing of the hypothesis? - Yes

• Do the statistical tests correctly test the results to allow differentiation of statistically significant results? - Yes

• Are the calculations valid in the light of the results? -Yes

• Did any results get omitted and why?– Extracorporeal cooling/unclear cooling methods

• Did they suggest any other areas of research?– Need further data before supporting therapeutic

hypothermia in; in-hospital arrests, asystole, non-cardiac aetiology

– Optimal cooling protocol

• Did they make any recommendations based on the results and were they appropriate?– Conventional cooling post-arrest seems to improve

survival. Reviewers findings support current ILCOR guidelines

• What level of evidence does the study represent? 1+/1-• What grade of recommendation can I make on this

result alone? A• Is the study relevant to my clinical practice? Yes

• What grade of evidence can I make when this study is considered along with other available evidence? A

• Should I change my practice because of these results? Yes

• Should I audit my current practice because of these results? Yes

Citation

ArrichJ, Holzer M, Herkner H, Mullner M. Hypothermia for neuroprotection in adults after cardiopulmonary resuscitation. Cochrane Database of Systematic Reviews 2009, Issue 4 Art no.: CD004128

SHAMELESS PLUG

Scottish Intensive Care SocietyEducation Meeting

Monday 25th and Tuesday 26th October 2010 Royal College of Physicians

Edinburgh

Approved for 10 CPD points !

http://www.scottishintensivecare.org.uk/meetings/index.htmFor programme and application form