Thread by @CritCareReviews

➡️ Death has always fascinated human civilisations
➡️ Not just the ending of a life, but either preparation for the afterlife or attempts to restore an existing life

A 🧵

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➡️ Ancient Egyptians preserved corpses via mummification for an afterlife
➡️ They removed internal organs, used embalming fluids, linen bandages, & intricate coffins
➡️ The wealthy had pyramids
➡️ Relatives, staff & pets were buried alive for the journey to the afterlife

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➡️ In Greek Mythology, the River Styx separated the worlds of the living & dead
➡️ Charon, the Ferryman, required payment from the deceased for passage
➡️ The dead were buried with a coin
➡️ Those unable to pay were left to wander the river bank for 100 years

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➡️ Mary Shelley's classic novel Frankenstein explored the theme of overcoming death
➡️ Dr Frankenstein created a living being by assembling body parts from the deceased
➡️ As a child, Shelly was fascinated by stories of electrical currents stimulating movement in corpses

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➡️ The modern management of cardiac arrest mirrors these themes
➡️ Resuscitation enables life to be snatched from the jaws of death
➡️ Post arrest management potentially allows the person to be saved
➡️ Many interventions have been tested

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➡️ Based on incredible stories of survival after prolonged immersion in freezing water or snow, hypothermia has been extensively investigated post arrest
➡️ Led by the TTM trials, numerous high quality studies have failed to convincingly demonstrate benefit from cooling

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➡️ Barbituates were developed by Adolf von Baeyer in 1864
➡️ They were introduced into clinical practice in 1904 for treatment of sleep disorders, seizures, and psychoses
➡️ The name barbituates may have come in honour of von Baeyer's friend Barbara

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➡️ In 1986, thiopental was tested post cardiac arrest
➡️ 262 comatose survivors were randomised to 1 dose of 30 mg/kg or placebo
➡️ 1 year outcomes were similar
🔴 survival - 77 v 80%
🔴 neuro recovery - good 20 v 15% | poor 2 v 5%
➡️ Neither did it work taken pre-arrest

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➡️ Xenon was discovered in 1898 by British chemists William Ramsay & Morris Travers
➡️ It was first used clinically as an anaesthetic agent in 1951 by American Stuart Cullen
➡️ In animal models, xenon has neuroprotective effects post cardiac arrest

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➡️ Xenon was tested in 2016 in 110 comatose patients after OHCA
➡️ Patients were randomised to inhaled xenon or not
➡️ Both groups were treated at 33C
➡️ Xenon resulted in
🔴 less white matter damage
🔴 similar functional outcomes
🔴 similar mortality at 6/12 (27% vs 34%)

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➡️ Exenatide is a glucagon-like peptide-1 analog used for the management of diabetes mellitus
➡️ It was first isolated by John Eng in 1992
➡️ Exenatide has various neuroprotective effects, including reducing cerebral infarction volume

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➡️ It was tested in an RCT in 2016
➡️ 120 comatose patients after out-of-hospital cardiac arrest were randomised to exenatide or placebo
➡️ Brain injury, as measured by neuron specific enolase levels, were similar between groups
➡️ Functional outcomes were also similar

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➡️ Calcium channel blockers may limit the ischaemia-induced entry of calcium into cells
➡️ Nimodipine is widely used in aneurysmal subarachnoid haemorrhage for the prevention of delayed cerebral ischaemia
➡️ However, the exact mechanism of action in aSAH remains unclear

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➡️ in 1990, 155 patients after out-of-hospital VF cardiac arrest were randomised to IV nimodipine or placebo
🔴 One year survival was similar (40% vs 36%)
🔴 Nimodipine resulted in less recurrent VF

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➡️ Lidoflazine is also a calcium channel blocker
➡️ A trial in 1991 randomised 520 comatose cardiac arrest survivors to lidoflazine or placebo
➡️ 6 month outcomes were similar
🔴 survival - 82 v 83%
🔴 neuro recovery - good 15 v 13% | poor 1.2 v 1.9%

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➡️ A hormone was first postulated as an erythropoiesis stimulating agent in 1905 by Paul Carnot
➡️ Erythropoietin has a range of effects across different tissues
➡️ The brain has Epo receptor–expressing cells & erythropoietin may have potential neuroprotective effects

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➡️A French trial randomised 476 patients post OHCA to IV erythropoietin or not
➡️5 IV doses of 40K units were given
🔴At day 60, the % with CPC scores of 1 were similar in each group - 32% v 32%
🔴The epo group suffered more adverse events, including thromboses (12 v 6%)

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➡️ Although adequate cerebral perfusion is necessary for neuronal activity, the optimal blood pressure post cardiac arrest is unknown
➡️ Targeting too high a pressure risks further myocardial damage
➡️ Too low a pressure risks cerebral ischaemia

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➡️ In 2022, the BOX trial compared mean arterial pressure targets of 77 with 63 mmHg in 789 pts post OHCA
➡️ Outcomes were similar between groups
🔴 Composite primary outcome of death or poor neuro recovery (34% vs 32%)
🔴 Day 90 mortality 31% v 29%

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➡️ Hyperoxia has been associated with worse outcomes across a range of conditions, including cardiac arrest
➡️ By targeting a lower oxygen level, hyperoxia may be avoided
➡️ However, hypoxia's not great either for an injured brain....

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➡️2 large trials were published in 2022 investigating oxygenation post cardiac arrest
➡️The Australian EXACT trial compared SpO2s of 90-94% with 98-100% in 428 pts
➡️The Danish BOX trial compared 9-10 with 13-14 kPa in 789 pts
🔴Group outcomes were similar in both trials

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➡️ Carbon dioxide has many physiological effects relevant to cardiac arrest
➡️ It is a major determinant of cerebral blood flow, potentially increasing cerebral perfusion without use of injurious catecholamines
➡️ It is also anticonvulsant, anti-inflammatory & antioxidant

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➡️The Finnish COMACARE trial examined low (4.5–4.7) & high (5.8–6.0 kPa) PaCO2 in 120 patients post OHCA
🔴Median serum NSE levels were similar at 48 hours - 18.8 v 22.5 μg/l
🔴Notably, the median cerebral oxygen saturation was higher in the high-normal PaCO2 group

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➡️ The Australian pilot CCC trial also compared low (4.7-6.0) & high (6.7-7.3 kPA) PaCO2 levels in 86 patients post cardiac arrest
➡️ The trial demonstrated the intervention was feasible & safe

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➡️ With other interventions proving disappointing, the role for targeted therapeutic mild hypercapnia remains open
➡️ Any effective therapy would be significant
🔴 > 356,000 OHCAs in the USA pa
🔴 <50% who reach hospital survive
🔴 7% survive with good neuro recovery

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➡️ Join us in @TitanicBelfast to hear the results of the international @TAMEtrial at #CCR23
➡️ @Eastwoodgm will present the results with Alistair Nichol

➡️ Will we soon be providing targeted therapeutic mild hypercapnia?

🚩Registration is open criticalcarereviews.com/meetings/ccr23

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@TitanicBelfast @TAMEtrial @Eastwoodgm ➡️ #CCR23 is supported by

🔴 @VisitBelfast
🔴 @belfastcc
🔴 @NITouristBoard
🔴 @BelfastTrust

See you in Belfast in June

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@TitanicBelfast @TAMEtrial @Eastwoodgm @VisitBelfast @belfastcc @NITouristBoard @BelfastTrust References

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