Editing Lethal injection (section)

===Conventional lethal injection protocol===
Typically, three drugs are used in lethal injection. [[Pancuronium bromide]] (Pavulon) is used to cause muscle paralysis and decreased neural transmission to the lungs, [[potassium chloride]] to stop the heart, and [[midazolam]] for sedation.<ref>{{cite web |url=https://www.amnesty.org/en/news-and-updates/news/Lethal-injections-lead-doctors-to-break-medical-oath-041007 |title=Lethal injections lead doctors to break medical oath |publisher=Amnesty International |date=October 4, 2007 |url-status=live |archive-url=https://web.archive.org/web/20140423183309/http://www.amnesty.org/en/news-and-updates/news/Lethal-injections-lead-doctors-to-break-medical-oath-041007 |archive-date=April 23, 2014 |df=mdy-all }}</ref><ref>Amnesty International:"Execution by lethal injection: A quarter century of state poisoning" https://www.amnesty.org/en/documents/ACT50/007/2007/en/</ref>

====Pancuronium bromide (Pavulon)====
{{Main|Pancuronium}}
*Lethal injection dosage: 100 milligrams

Pancuronium bromide (Trade name: Pavulon): The related drug [[curare]], like pancuronium, is a [[neuromuscular-blocking drug|non-depolarizing muscle relaxant]] (a [[paralytic]] agent) that blocks the action of [[acetylcholine]] at the motor end-plate of the [[neuromuscular junction]]. Binding of acetylcholine to receptors on the end-plate causes depolarization and contraction of the muscle fiber; non-depolarizing neuromuscular blocking agents like pancuronium stop this binding from taking place

The typical dose for pancuronium bromide in capital punishment by lethal injection is 0.2&nbsp;mg/kg and the duration of paralysis is around 4 to 8 hours. Paralysis of respiratory muscles will lead to death in a considerably shorter time.

Pancuronium bromide is a derivative of the [[alkaloid]] [[malouetine]] from the plant ''Malouetia bequaertiana''.<ref>{{Cite journal |title=Prelude to pancuronium and vecuronium |journal=Anaesthesia |volume=55 |issue=6 |pages=551–6 |doi=10.1046/j.1365-2044.2000.01423.x |pmid=10866718 |year=2000 |last1=McKenzie |first1=A. G. |s2cid=22476701 |doi-access= }}</ref>

Instead of pancuronium, other drugs in use are [[suxamethonium chloride|succinylcholine chloride]] and [[tubocurarine chloride]].

====Potassium chloride====
{{Main|Potassium chloride}}
*Lethal injection dosage: 100 mEq ([[milliequivalent]]s)

[[Potassium]] is an [[electrolyte]], 98% of which is intracellular. The 2% remaining outside the cell has great implications for cells that generate action potentials. Doctors prescribe potassium for patients when potassium levels in the blood are insufficient, called [[hypokalemia]]. The potassium can be given orally, which is the safest route; or it can be given intravenously, in which case strict rules and hospital protocols govern the rate at which it is given.

The usual intravenous dose of 10–20 mEq per hour is given slowly since it takes time for the electrolyte to equilibrate into the cells. When used in state-sanctioned lethal injection, bolus potassium injection affects the electrical conduction of heart muscle and ultimately leads to cardiac arrest. The potassium bolus delivered for lethal injection causes a rapid onset of elevated extracellular potassium, also known as [[hyperkalemia]], causing [[depolarization]] of the resting membrane potential of the heart muscle cells, particularly impacting the heart's pacemaker cells. However, potassium's effect on membrane potential is concentration dependent and ultimately occurs in two phases. Given the reference range for serum potassium is 3.5-5.5 mEq/L, concentrations up to 8 mEq/L shorten action potential duration and the refractory period due to an allosteric effect of potassium ions on potassium channels, leading to increased conduction velocity and subsequently quicker potassium efflux which contributes to quicker repolarization and the mentioned shortening of the refractory period.<ref name=":6">{{Cite journal |last1=Weiss |first1=James N. |last2=Qu |first2=Xhilin |last3=Shivkumar |first3=Kalyanam |date=March 2017 |title=The Electrophysiology of Hypo- and Hyperkalemia |journal=Circulation: Arrhythmia and Electrophysiology |volume=10 |issue=3 |doi=10.1161/CIRCEP.116.004667 |pmid=28314851 |pmc=5399982 }}</ref><ref>{{Citation |last=Rastegar |first=Asghar |title=Serum Potassium |date=1990 |work=Clinical Methods: The History, Physical, and Laboratory Examinations |editor-last=Walker |editor-first=H. Kenneth |url=https://www.ncbi.nlm.nih.gov/books/NBK307/ |access-date=2024-08-16 |edition=3rd |place=Boston |publisher=Butterworths |isbn=978-0-409-90077-4 |pmid=21250149 |editor2-last=Hall |editor2-first=W. Dallas |editor3-last=Hurst |editor3-first=J. Willis}}</ref> At approximately 8 mEq/L and beyond, the shortened refractory period and increased resting membrane potential diminishes the quantity of voltage-gated sodium channels ready to contribute to rapid phase 0 depolarization due to the inactivation gate requiring further repolarization to open back up.<ref name=":6" /> At potassium concentrations beyond 14mEq/L, enough sodium channels remain inactivated to no longer generate an action potential, ultimately leading to no heart beat.<ref name=":6" /> Heart potassium levels after lethal injection can reach 160.0 mEq/L.<ref>{{Cite journal |last1=Bertol |first1=Elisabetta |last2=Politi |first2=Lucia |last3=Mari |first3=Francesco |date=January 2012 |title=Death by potassium chloride intravenous injection: evaluation of analytical detectability |url=https://pubmed.ncbi.nlm.nih.gov/21923800/ |journal=Journal of Forensic Sciences |volume=57 |issue=1 |pages=273–275 |doi=10.1111/j.1556-4029.2011.01907.x |issn=1556-4029 |pmid=21923800}}</ref> 

Depolarizing the muscle cell inhibits its ability to fire by reducing the available number of sodium channels (they are placed in an inactivated state). [[ECG]] changes vary depending on serum potassium concentrations and on the individual. Peaked T-waves signifying faster repolarization and potentially instances of early-repolarization and phase 2 re-entry (Brugada, Short QT, and Early-Repolarization Syndromes) are evident in the first phase of hyperkalemia.<ref name=":6" /> This progresses into a broadening and lengthening of the P wave and PR interval, then eventually disappearance of the P wave, widening of the QRS complex, and finally, [[asystole]]. This process can occur in the span of 30 to 60 seconds, but there have been cases of 'botched' procedures, leading to one inmate gasping for air for approximately 10 to 13 minutes.<ref>{{Cite news |date=2018-03-05 |title=Life and Death Row: How the lethal injection kills |url=https://www.bbc.co.uk/bbcthree/article/cd49a818-5645-4a94-832e-d22860804779 |access-date=2024-08-16 |work=BBC Three |language=en-GB}}</ref> 

====Sodium thiopental====
{{Main|Sodium thiopental}}
*Lethal injection dosage: 2–5&nbsp;grams

Sodium thiopental (US trade name: Sodium Pentothal) is an ultra-short acting barbiturate, often used for anesthesia induction and for medically induced coma. The typical anesthesia induction dose is 0.35 grams. Loss of consciousness is induced within 30–45 seconds at the typical dose, while a 5&nbsp;gram dose (14 times the normal dose) is likely to induce unconsciousness in 10 seconds.

A full medical dose of thiopental reaches the brain in about 30 seconds. This induces an unconscious state. Five to twenty minutes after injection, approximately 15% of the drug is in the brain, with the rest in other parts of the body.

The [[half-life]] of this drug is about 11.5 hours,<ref>{{cite journal |pmid=7235274 |title=Pharmacokinetics and plasma binding of thiopental. I: Studies in surgical patients |year=1981 |last1=Morgan |first1=DJ |last2=Blackman |first2=GL |last3=Paull |first3=JD |last4=Wolf |first4=LJ |volume=54 |issue=6 |pages=468–73 |journal=Anesthesiology |doi=10.1097/00000542-198106000-00005|doi-access=free }}</ref> and the concentration in the brain remains at around 5–10% of the total dose during that time. When a 'mega-dose' is administered, as in state-sanctioned lethal injection, the concentration in the brain during the tail phase of the distribution remains higher than the peak concentration found in the induction dose for anesthesia, because repeated doses—or a single very high dose as in lethal injection—accumulate in high concentrations in body fat, from which the thiopental is gradually released.<ref name="THIOPENTAL SODIUM"/> This is the reason why an ultra-short acting barbiturate, such as thiopental, can be used for long-term induction of medical [[coma]].

Historically, thiopental has been one of the most commonly used and studied [[drugs]] for the induction of coma. Protocols vary for how it is given, but the typical doses are anywhere from 500&nbsp;mg up to 1.5&nbsp;grams. It is likely that this data was used to develop the initial protocols for state-sanctioned lethal injection, according to which one gram of thiopental was used to induce the coma. Most states use 5&nbsp;grams to be absolutely certain the dosage is effective.

[[Pentobarbital]] was introduced at the end of 2010 due to a shortage of sodium thiopental,<ref name="cnn20101216" /> and has since become the primary sedative in lethal injections in the United States.<ref name="state-lethal-injection" />

Barbiturates are the same class of drug used in medically assisted suicide. In euthanasia protocols, the typical dose of thiopental is 1.5&nbsp;grams; the Dutch Euthanasia protocol indicates 1-1.5 grams or 2 grams in case of high barbiturate tolerance.<ref name=euthanasics/> The dose used for capital punishment is therefore about 3 times more than the dose used in euthanasia.