➡️The history of resuscitation in cardiac arrest is long and fascinating
➡️Over time, four components have emerged to provide the central basis for saving an apnoeic, pulseless person just minutes from death
A thread.....
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➡️Perhaps the earliest reference to artificial breathing comes from the Egyptian Goddess Isis
➡️She resuscitated her dead husband (who was also her brother...) by breathing into his mouth
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➡️The Greek physician Galen was the first to describe artificial ventilation with his famous quote:
➡️"If you take a dead animal & blow air through its larynx through a reed, you will fill its bronchi and watch its lungs attain the greatest distention"
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➡️Over time scientific focus was misplaced, with attempts at supported breathing becoming less insightful
➡️Efforts at artificial ventilation with tobacco smoke, using a bellows placed in the anus, proved disappointing
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➡️In 1732, the British surgeon William Tossach resuscitated coal miner James Blair using mouth-to-mouth ventilation
➡️"there was not the least pulse in either Heart or Arteries, & not the least Breathing could be observed"
➡️By 4 hours, the miner was conscious & walking
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➡️In 1782, the Royal Humane Society advocated the use of bellows to replace mouth-to-mouth ventilation, which was deemed "vulgar" by the English members
➡️Their recommendation included the use of cricoid pressure to prevent gastric aspiration
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➡️In 1958, Peter Safar and James Elam, two American anesthesiologists, demonstrated the efficacy of mouth-to-mouth ventilation by performing it on paralysed volunteers.
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➡️In 1628, the English physician William Harvey published his treatise de Motu Cordis describing the circulation
➡️The heart pumped blood to organs via arteries, which returned via veins
➡️As this contradicted the centuries old paradigm of Galen, Harvey was ridiculed
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➡️Attempts to provide an artificial circulation included placing a patient over a barrel and rolling it, or over a horse, which ran generating episodic vertical force on the chest
➡️However, these manoeuvres were likely intended to produce chest movement for ventilation
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➡️In 1883, Franz Koenig described external cardiac massage by pressing at the expected site of the apex beat at 30-40 beats per minute
➡️This restored spontaneous circulation in a patient who had cardiac arrest accidentally induced by chloroform anesthesia
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➡️Mechanical chest compression devices first appeared in the early 1960s, beginning with the “electro-pneumatic machine” of Harkins & Bramson
➡️It was quickly followed by other machines, including the “Beck-Rand external cardiac compression machine” of Safar in 1963
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➡️Luigi Galvani, an Italian physicist in the late 1700s, thought he had discovered a means of restoring life
➡️Using electrical currents, he stimulated amputated frog legs to move
➡️Galvani envisioned a means of resuscitating the dead with electricity
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➡️In 1802, Galvani's nephew, Giovanni Aldini, promoted his uncle's work in London
➡️He acquired the body of a recently hung man & applied electrical currents
➡️Aldini astounded his audience by stimulating eye opening, facial movements, head turning and a clenched fist
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➡️After opening the deceased's chest, Aldini tried to restart the heart with directly applied electricity, but was unsuccessful
➡️One member of the audience was reported as dying that night at home from shock
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➡️Mary Shelly, the author of Frankenstein, was influenced by these report of electrically induced movements of the dead.
➡️Anthony Carlisle, a medic who attended these exhibitions, was a good friend of her father
➡️Shelly hid under the table to hear these stories
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➡️In 1940, the American physiologist Carl Wiggers, demonstrated the how an externally applied electrical current could stop a heart fibrillating
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➡️In 1947, American cardiac surgeon Claude Beck successfully internally defibrillated a 14-year-old boy who suffered ventricular fibrillation during a thoracoplasty for a congenital chest deformity
➡️This occurred after 45 minutes of cardiac massage
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➡️In 1956, American Cardiologist Paul Zoll reported the first successful closed-chest external defibrillation in a man with recurrent syncope that caused ventricular fibrillation
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➡️Belfast cardiologist Frank Pantridge, working at the Royal Victoria Hospital, was the first to introduce a mobile defibrillator (1965) and out-of-hospital cardiac resuscitation service (1966)
➡️The defibrillator weighed 70 lbs & was powered by the ambulance engine
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➡️In 1885, George Oliver and Edward Schäfer of the University of London discovered an adrenal gland extract which acted on the blood vessels & heart, causing arteriolar constriction & increases in heart rate, ventricular contraction & blood pressure
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➡️In 1897, the active compound was isolated by John Abel, at John Hopkins University, & called epinephrine
➡️In 1900, Japanese biochemist Jōkichi Takamine also purified an adrenal compound he named adrenalin
➡️British physiologist Starling used the term adrenaline
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➡️Thus began the old trans-atlantic naming debate
➡️Interestingly, the derivations of the names differ too
➡️adrenaline derives from the latin roots “ad” and “renes” (near the kidney)
➡️epinephrine from the Greek roots “epi” and “nephros” (on the kidney).
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➡️The administration of adrenaline in cardiac arrest was first attributed to Crile and Dolley in 1906
➡️Pearson and Redding described perhaps the first animal study demonstrating the effectiveness of adrenaline for the management of canine cardiac arrest in 1963
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➡️Despite a long history of the development of the various elements of modern CPR, global outcomes for people suffering out-of-hospital cardiac arrest remain poor
➡️Just 29.7% survive to hospital admission
➡️8.8% survive to hospital discharge
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➡️In 2015, Bernard reported the results of the observational CHEER study, describing an incredible 54% survival with good neurological recovery in 26 patients with prolonged cardiac arrest
➡️Were the 4 key elements of resuscitation going to be added to?
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The intervention consisted of
➡️mechanical CPR
The intervention consisted of
➡️mechanical CPR
➡️intra-arrest induced hypothermia
➡️ECMO
➡️early reperfusion PCI strategy
➡️ECMO commenced at a median of 56 mins post collapse
➡️96% obtained ROSC
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➡️In 2020, Yannopoulos reported the randomised controlled ARREST trial, comparing ECMO facilitated resuscitation with standard ACLS treatment in 30 patients with OHCA & refractory ventricular fibrillation
➡️1/15 ACLS vs 6/14 ECMO survived to hospital discharge
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➡️Despite the encouraging results, these two studies were small
➡️Enter the Prague OHCA study, investigating mechanical chest compression, intra-arrest head cooling, transport to hospital, extracorporeal life support and immediate coronary reperfusion
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Survival with good neurological outcome at 180 days occurred in
➡️31.5% in the invasive strategy group
➡️22.0% in the standard resuscitation group
Odds ratio 1.63; 95% CI, 0.93 to 2.85
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➡️Will eCPR be the latest addition to our choice of interventions to manage OHCA?
➡️Join us at #CCR22 to hear Jan Belohlavek (@jan_belohlavek) present the Prague OHCA study and find out!
➡️ Antimicrobial therapy has been used for millennia
➡️ Treating severe infections can be lifesaving
➡️ However, the widespread use of antimicrobials also has downsides
A 🧵
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➡️ Throughout history, honey, herbs & metals were often used
➡️ One of the earliest known antimicrobial therapies was the topical use of mouldy bread
➡️ This intervention has been recorded in many ancient civilisations, including Egypt, China, Serbia, Greece & Rome
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➡️ Mercury was used for epidemic diseases since the 1300s & especially syphilis
➡️ However, the treatment could be worse than the disease, with mercury poisoning possible
➡️ Treatment could last years, leading to the saying “A night with Venus, a lifetime with mercury”"
➡️ Throughout history, the most mystical substance of all has been blood
➡️ It has been coveted and desired
➡️ Fought for and defended
➡️ Stolen, yet freely given
A 🧵
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➡️ Blood has always been a symbol of power
➡️ In Greek mythology, ichor, the blood of the Gods, was a golden fluid
➡️ It was immortal, pure, & untainted by human weaknesses
➡️ The Gods derived their divine powers & longevity from it
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➡️ Blood has been revered for its restorative properties
➡️ Elizabeth Báthory, a 16th-century Hungarian noblewoman, allegedly killed hundreds of young girls & women
➡️ She bathed in their blood to maintain her youth & beauty
➡️ There are ~ 5.8 million trauma deaths per year globally
➡️ Trauma is the largest cause of death below the age of 50
➡️ One-third of severely injured trauma patients are coagulopathic at hospital arrival
➡️ Fibrinogen is often used, but is it effective?
a short 🧵
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➡️ Trauma-induced coagulopathy is due to inflammation & shock
➡️ It is worsened by hypothermia, acidosis, and hemodilution
➡️ Coagulopathy due to hemorrhage is strongly associated with mortality
➡️ 1/3 of early trauma deaths are due to uncontrolled haemorrhage
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➡️ Fibrinogen is depleted early during major bleeding
➡️ It can be replaced with fresh frozen plasma, cryoprecipitate or fibrinogen concentrate
➡️ Cryoprecipitate includes fibrinogen, factor VIII coagulant, von Willebrand factor, fibronectin & factor XIII
➡️ 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
➡️It's widely used for treatment & prevention of haemorrhage
➡️It's in the WHO's List of Essential Medicines & recommended in the European Traumatic Haemorrhage guideline (2023)
➡️But is it as efficacious as we think?
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🚩 History
➡️Drs. Utako & Shosuke Okamoto invented TXA in 1962
➡️They identified that the amino acid lysine inhibited the degradation of plasmin, a profibrinolytic enzyme
➡️Lysine was modified to first produce Epsilon- Amino-Caproic Acid and later TXA, x 27 more potent
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🚩 Pharmacology
➡️TXA is a molecular analog of lysine
➡️It inhibits fibrinolysis by preventing the binding of plasminogen to fibrin
➡️This inhibits plasmin formation & displaces plasminogen from the fibrin surface
➡️It also has effects on the immune system & inflammation