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Lethal injection involves injecting a person with fatal doses of poisonous drugs to cause death. The main applications are euthanasia, suicide and capital punishment (the last of which is the focus of this article). As a method for capital punishment, lethal injection gained popularity in the twentieth century as form of execution meant to supplant methods – such as electrocution, hanging, firing squad, gas chamber, or decapitation – that were considered to be less humane. The humaneness of lethal injection has been debated. (See "Controversy," below.) It is now the most common form of execution in the United States: every American execution in 2005 was conducted by lethal injection. 
- 1 History
- 2 Procedure in US executions
- 3 Lethal injection drugs
- 4 Euthanasia protocol
- 5 Constitutionality in the United States
- 6 Ethics of lethal injection
- 7 Controversy: Arguments against
- 8 Controversy: Arguments in support
- 9 See also
- 10 Resources
- 11 References
The concept of lethal injection was first proposed in 1888 by Julius Mount Bleyer, a New York doctor who praised it as being cheaper and more humane than hanging. Bleyer's idea, however, was never used. The British Royal Commission on Capital Punishment (1949–53) also considered lethal injection, but eventually rejected it after pressure from the British Medical Association (BMA).
In 1977 Oklahoma's state medical examiner, Jay Chapman, proposed a new, 'more humane' method of execution, known as Chapman's Protocol: "An intravenous saline drip shall be started in the prisoner's arm, into which shall be introduced a lethal injection consisting of an ultra-short-acting barbiturate in combination with a chemical paralytic." After being approved by anesthesiologist Stanley Deutsch, Reverend Bill Wiseman introduced the method into the Oklahoma legislature where it passed and was quickly adopted (Title 22, Section 1014(A)). Since then, thirty-seven of the thirty-eight states using capital punishment have introduced lethal injection statutes. (The sole exception is Nebraska, which continues to electrocute the condemned.) On 7 December 1982, Texas became the first state to use lethal injection as a capital punishment for the execution of Charles Brooks, Jr..
Execution by nitrogen asphyxiation was proposed in 1995 as an alternative to lethal injection and appears occasionally in online discussions, but as of 2021 is not used by any nation.
Procedure in US executions
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After the condemned is fastened on the execution table, two intravenous cannulae ("drips") are inserted, one in each arm. Only one is used for the execution; the other is reserved as a backup in case the primary line fails.
The arm of the subject is swabbed with alcohol before the cannula is inserted. The needles and equipment used are also sterilized. One reason for this is that cannulae are standard medical products that are sterilized during manufacture. Secondly, there is a chance that the prisoner could receive a stay of execution after the cannulae have been inserted, as happened in the case of James Autry in October 1983 (he was executed eventually on March 14 1984).
The intravenous injection is usually a sequence of compounds, designed to induce rapid unconsciousness followed by death through paralysis of respiratory muscles and/or by inducing cardiac arrest through depolarization of cardiac muscle cells. The execution of the condemned in most states involves three separate injections:
- Sodium thiopental: to render the offender unconscious.
- Pancuronium/Tubocurarine: to stop all muscle movement except the heart. This causes muscle paralysis, collapse of the diaphragm, and would eventually cause death by asphyxiation.
- Potassium chloride: stops the heart, and thus causes death: see cardiac arrest.
The drugs are not mixed externally as that can cause them to precipitate.
The intravenous tubing leads to a room next to the execution chamber, usually separated from the subject by a curtain or wall. Typically a technician trained in venipuncture inserts the syringe, while a second technician, who is usually a member of the prison staff, orders, prepares, and loads the drugs into an infusion pump. After the curtain is opened to allow the witnesses to see inside the chamber, the condemned person will then be permitted to make a final statement. Following this, the warden will signal for the execution to commence, and the executioner(s) (either prison staff or private citizens depending on the jurisdiction) will then activate the infusion pump which mechanically delivers the three drugs in sequence. During the execution, the subject's cardiac rhythm is monitored. Death is pronounced after cardiac activity stops. Death usually occurs within seven minutes, although the whole procedure can take up to 2 hours, as was the case with the execution of Christopher Newton on May 24 2007. According to state law, if participation in the execution is prohibited for physicians, the death ruling is made by the state's Medical Examiner's Office. After confirmation that death has occurred, a coroner signs the executed individual’s death certificate.
Lethal injection drugs
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The following drugs are a representation of a typical lethal injection as practiced in the United States for capital punishment.
- Lethal Injection dosage: 2-5 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 3-5 mg/kg (a person who weighs 200 pounds, or 91 kilograms, would get a dose of about 300 mg). Loss of consciousness is induced within 30-45 seconds at the typical dose, while a 5 gram dose - 14 times the normal dose - is likely to induce unconsciousness in 10 seconds.
Thiopental reaches the brain within seconds and attains a peak brain concentration of about 60% of the total dose in about 30 seconds. At this level, the subject is unconscious. Within 5 to 20 minutes the percentage in the brain falls to about 15% of the total dose, since the drug redistributes to the rest of the body. At this concentration in the brain, the anesthetic effects wear off and consciousness returns. These are the typical pharmacokinetics for the induction dose.
The half-life of this drug is about 11.5 hours , 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 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. This is the reason why an ultra-short acting barbiturate, such as thiopental, can be used for long-term induction of medical coma.
After a 5 gram dose consciousness will be regained in about 5 to 6 half-lives, which occurs in about 57-69 hours. The effects of such a high dose, however, include profound respiratory depression (depression of the brainstem respiratory center) and vascular collapse (vasodilatation and myocardial depression), which is in itself lethal.
Historically thiopental has been one of the most commonly used and studied drugs for the induction of coma. Protocols vary with how the medication is given, but the typical doses are anywhere from 500 mg up to 1.5 grams. It is likely that these data were used to develop the initial protocols for lethal injection of giving 1 gram of thiopental to induce the coma. Now, most states use 5 grams to be absolutely certain about its effectiveness.
Barbiturates are the same class of drugs used in medically assisted suicide. In euthanasia protocols, the typical dose of thiopental is 20 mg/kg  and a 91 kilogram man would receive 1.82 grams. The lethal injection dose used in capital punishment is therefore about 3 times more than the dose used in euthanasia.
- Lethal Injection dosage: 100 milligrams
Pancuronium bromide (Trade name: Pavulon) is a 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 fibre; non-depolarizing neuromuscular blocking agents like pancuronium stop this binding from taking place.
The typical dose for pancuronium bromide is 0.2 mg/kg (a person who weighs 200 pounds, or 91 kilograms, would get a dose of around 9 mg). With a 100 milligram dose, the onset of paralysis occurs in around 15 to 30 seconds, 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. 
- Lethal Injection dosage: 100 mEq (milliequivalents)
Potassium is an electrolyte that is 98% within the cells. The 2% remaining outside of the cell has great implications for cells that generate action potentials. Typically, doctors give patients potassium when there is insufficient potassium, called hypokalemia, in the blood. The potassium can be given orally, which is the safest route; or it can be given intravenously, in which case there are strict rules and hospital protocols on the rate at which it is given.
The usual intravenous dose is 10-20 mEq per hour and it is given slowly since it takes time for the electrolyte to equilibrate into the cells. When used in lethal injection, bolus potassium injection affects the electrical conduction of heart muscle. Elevated potassium, or hyperkalemia, causes the resting electrical potential of the heart muscle cells to be higher than normal. Without a negative resting potential, cardiac cells cannot generate impulses that lead to contraction.
Depolarizing the muscle cell inhibits its ability to fire by reducing the available number of Na channels (they are placed in an inactivated state). EKG changes include faster repolarization (peaked T-waves), PR interval prolongation, widening of the QRS, and eventual sine-wave formation and asystole. The heart eventually pops in diastole. Cases of patients dying from hyperkalemia (usually secondary to renal failure) are well known in the medical community, where patients have been known to die very rapidly, having previously seemed to be normal.
Euthanasia can be accomplished either through oral, intravenous, or intramuscular administration of drugs. In individuals who are incapable of swallowing lethal doses of medication, an intravenous route is preferred. The following is a Dutch protocol for parenteral (intravenous) administration to obtain euthanasia, with the old protocol listed first and the new protocol listed second:
- First a coma is induced by intravenous administration of 1 g thiopental sodium (Nesdonal®), if necessary, 1.5-2 g of the product in case of strong tolerance to barbiturates. Then 45 mg alcuronium chloride (Alloferin®) or 18 mg pancuronium bromide (Pavulon®) is injected. In order to ensure optimal availability, these agents are preferably given intravenously. However, there are substantial indications that they can also be injected intramuscularly. In severe hepatitis or cirrhosis of the liver, alcuronium is the agent of first choice.
- Intravenous administration is the most reliable and rapid way to accomplish euthanasia and therefore can be safely recommended. A coma is first induced by intravenous administration of 20 mg/kg thiopental sodium in a small volume (10 ml physiological saline). Then a triple intravenous dose of a non-depolarizing neuromuscular muscle relaxant is given, such as 20 mg pancuronium bromide or 20 mg vecuronium bromide (Norcuron®). The muscle relaxant should preferably be given intravenously, in order to ensure optimal availability. Only for pancuronium dibromide are there substantial indications that the agent may also be given intramuscularly in a dosage of 40 mg.
Constitutionality in the United States
In 2006, the Supreme Court ruled in Hill v. McDonough that death-row inmates in the United States could challenge the constitutionality of states' lethal injection procedures through a federal civil rights lawsuit. Since then, numerous death-row inmates have brought such challenges in the lower courts, claiming that lethal injection as currently practiced violates the ban on "cruel and unusual punishment" found in the Eighth Amendment to the United States Constitution. Lower courts evaluating these challenges have reached opposing conclusions. For example, courts have found that lethal injection as practiced in California,Florida, and Tennessee is unconstitutional. On the other hand, courts have found that lethal injection as practiced in Missouri, Arizona, and Oklahoma is constitutionally acceptable. On September 25, 2007, the United States Supreme Court agreed to hear a lethal injection challenge arising from Kentucky, Baze v. Rees.. In Baze, the Supreme Court will address whether Kentucky's particular lethal injection procedure comports with the Eighth Amendment and will determine the proper legal standard by which lethal injection challenges in general should be judged, all in an effort to bring some uniformity to how these claims are handled by the lower courts. As of late September 2007, there is uncertainty over whether executions in the United States will be put on hold during the period in which the United States Supreme Court is considering the constitutionality of lethal injection.
Ethics of lethal injection
The American Medical Association believes that a physician's opinion on capital punishment is a personal decision. Since the AMA is founded on preserving life, they argue that a doctor "should not be a participant" in executions in any form with the exception of "certifying death, provided that the condemned has been declared dead by another person." Amnesty International argues that the AMA's position effectively "prohibits doctors from participating in executions."  The AMA, though, does not have the authority to prohibit doctors from participation in lethal injection, nor does it have the authority to revoke medical licenses, since this is the responsibility of the individual states.
Typically, most states do not require that physicians administer the drugs for lethal injection, but many states do require that physicians be present to pronounce or certify death.
Controversy: Arguments against
Opponents of lethal injection believe that it is not actually humane as practiced in the United States. Opponents argue that the thiopental is an ultra-short acting barbiturate that may wear off (anesthesia awareness) and lead to consciousness and an excruciatingly painful death wherein the inmate is unable to express their pain because they have been rendered paralyzed by the paralytic agent.
Opponents point to the fact that sodium thiopental is typically used as an induction agent and not used in the maintenance phase of surgery because of its short acting nature. Following the administration of thiopental, pancuronium bromide is given. Opponents argue that pancuronium bromide not only dilutes the thiopental, but (since the inmate is paralyzed) also prevents the inmate from expressing pain. Additional concerns have been raised over whether inmates are administered an appropriate level of thiopental due to the body's ability to quickly metabolize the drug, even after execution. Teresa Zimmers, a molecular biologist from the University of Miami Miller School of Medicine, has commented that the amount of thiopental administered to those being executed "would be an unacceptably low dose if the inmate was a pig scheduled for euthanasia."
Additionally, opponents argue that the method of administration is also flawed. They state that since the personnel administering the lethal injection lack expertise in anesthesia the risk of failing to induce unconsciousness is greatly increased. Also, they argue that the dose of sodium thiopental must be customized to each individual patient, not restricted to a set protocol. Finally, the remote administration results in an increased risk that insufficient amounts of the lethal injection drugs enter the bloodstream.
In total, opponents argue that the effect of dilution or improper administration of thiopental is that the inmate dies an agonizing death through suffocation due to the paralytic effects of pancuronium bromide and the intense burning sensation caused by potassium chloride.
Opponents of lethal injection as currently practiced argue that the procedure employed is entirely unnecessary and is aimed more towards creating the appearance of serenity and a humane death than an actually humane death. More specifically, opponents object to the use of Pancuronium bromide. They argue that its use in lethal injection serves no purpose, since there is no need to keep the inmate completely immobilized when the inmate is physically restrained. The actual function of pancuronium bromide in the lethal injection procedure is to suppress the autonomous nervous system, specifically to stop breathing, not as a function of restraint it is argued.
In 2005, University of Miami researchers, in cooperation with an attorney representing death row inmates, published a research letter in the medical journal The Lancet. The article presented protocol information from Texas and Virginia which showed that executioners had no anaesthesia training, drugs were administered remotely with no monitoring for anaesthesia, data were not recorded and no peer-review was done. Their analysis of toxicology reports from Arizona, Georgia, North Carolina, and South Carolina showed that post-mortem concentrations of thiopental in the blood were lower than that required for surgery in 43 of 49 executed inmates(88%); 21 (43%) inmates had concentrations consistent with awareness.  This led the authors to conclude that there was a substantial probability that some of the inmates were aware and suffered extreme pain and distress during execution. The authors attributed the risk of consciousness among inmates to the lack of training and monitoring in the process, but carefully make no recommendations on how to alter the protocol or how to improve the process. Indeed, the authors conclude, "because participation of doctors in protocol design or execution is ethically prohibited, adequate anaesthesia cannot be certain. Therefore, to prevent unnecessary cruelty and suffering, cessation and public review of lethal injections is warranted."
Paid expert consultants on both sides of the lethal injection debate have found opportunity to criticize the Lancet article. Subsequent to the initial publication in the Lancet, three letters to the editor and a response from the authors extended the analysis. The issue of contention is whether Thiopental, like many lipid-soluble drugs, may be redistributed from blood into tissues after death, effectively lowering thiopental concentrations over time, or whether Thiopental may distribute from tissues into the blood, effectively increasing post-mortem blood concentrations over time. Given the near-absence of scientific, peer-reviewed data on the topic of thiopental post-mortem pharmacokinetics, the controversy continues in the lethal injection community and in consequence, many legal challenges to lethal injection have not used the Lancet article.
In 2007 the same group that authored the Lancet study extended their study of the lethal injection process through a critical examination of the pharmacology of the barbiturate thiopental. This study published in the online journal PloS Medicine confirmed and extended the conclusions made in the Lancet article and go further to disprove the assertion that the lethal injection process is humane. To date these two studies by the University of Miami team serve as the only critical peer-reviewed examination of the pharmacology of the lethal injection process. These findings also appear to be further supported by increased reporting of problematic lethal injections in the United States.
The opponents say that because death can be painlessly accomplished, without risk of consciousness, by the injection of a single large dosage of barbiturate, the use of any other chemicals is entirely superfluous and only serves to unnecessarily increase the risk of torture during the execution. Another possibility would be the use of a fast-acting narcotic, such as fentanyl, which is widely used for inducing anesthesia for the entire duration of a short operation. To prevent the inmate waking up too soon, the injection could be repeated before the blood-level falls.
Cruel and unusual
On occasion, there have also been difficulties inserting the intravenous needles, sometimes taking over half an hour to find a suitable vein. Typically, the difficulty is found in convicts with a history of intravenous drug abuse. Opponents argue that the insertion of intravenous lines that take excessive amounts of time are tantamount to be cruel and unusual punishment. In addition, opponents point to instances where the intravenous line has failed, or where there have been adverse reactions to drugs, or unnecessary delays during the process of execution.
On December 13, 2006, Angel Nieves Diaz was not executed successfully in Florida using a standard lethal injection dose. Diaz was 55 years old, and had been sentenced to death for murder. Diaz did not succumb to the lethal dose even after 35 minutes, he required a second dose of drugs to complete the execution. At first a prison spokesperson denied Diaz had suffered pain and claimed the second dose was needed because Diaz had some sort of liver disease. After performing an autopsy, the Medical Examiner, Dr. William Hamilton, stated that Diaz’s liver appeared normal, but that the needle had been pierced through Diaz’s vein into his flesh. The deadly chemicals had subsequently been injected into soft tissue, rather than into the vein. Two days after the execution, Governor Jeb Bush suspended all executions in the state and appointed a commission “to consider the humanity and constitutionality of lethal injections.”
A study published in 2007 in the peer-reviewed journal PLoS Medicine suggested that "the conventional view of lethal injection leading to an invariably peaceful and painless death is questionable".
Controversy: Arguments in support
The combination of a barbiturate induction agent and a nondepolarizing paralytic agent is used in thousands of anaesthetics every day. Supporters of the death penalty argue that unless anesthesiologists have been wrong for the last 40 years, the use of pentothal and pancuronium is safe and effective. In fact, potassium is given in heart bypass surgery to induce cardioplegia. Therefore, the combination of these three drugs is still in use today. Supporters of the death penalty speculate that the designers of the lethal injection protocols intentionally used the same drugs as used in every day surgery to avoid controversy. The only modification is that a massive coma-inducing dose of barbiturates is given. In addition, similar protocols have been used in countries that support euthanasia or physician-assisted suicide. 
Thiopental is a rapid and effective drug for inducing unconsciousness, since it causes loss of consciousness upon one circulation through the brain due to its high lipophilicity. Only a few other drugs, such as methohexital, etomidate, propofol, or fentanyl have the capability to induce anesthesia so rapidly. Supporters argue that since the thiopental is given at a much higher dose than for medically-induced coma protocols, it is effectively impossible for a patient to wake up.
Anesthesia awareness occurs when general anaesthesia is inadequately maintained, for a number of reasons. Typically, anaesthesia is induced with an intravenous drug, but maintained with an inhaled anesthetic given by the anesthesiologist (note that there are several other methods of safely and effectively maintaining anesthesia). Barbiturates are used only for induction of anesthesia and these drugs rapidly and reliably induce anesthesia, but wear off quickly. A neuromuscular blocking drug may then be given to cause paralysis which facilitates intubation, although this is not always required. The anesthesiologist has the responsibility to ensure that the maintenance technique (typically inhalational) is started soon after induction to prevent the patient from waking up.
General anesthesia is not maintained with barbiturate drugs. An induction dose of thiopental wears off after a few minutes because the thiopental redistributes from the brain to the rest of the body very quickly. However, it has a long half-life, which means that it takes a long time for the drug to be eliminated from the body. If a very large initial dose is given, little or no redistribution takes place (since the body is saturated with the drug), which means that recovery of consciousness requires the drug to be eliminated from the body, which is not only slow (taking many hours or days), but unpredictable in duration, making barbiturates very unsatisfactory for maintenance of anaesthesia.
The "ultra-short" acting thiopental has a half-life of approximately 11.5 hours (however, the action of a single dose is terminated within a few minutes by redistribution of the drug from the brain to peripheral tissues) and the long acting phenobarbital has a half-life of approximately 4-5 days. It contrasts towards the inhaled anesthetics have extremely short half-lives and allow the patient to wake up rapidly and predictably after surgery.
The average time to death once a lethal injection protocol has been started is about 7-11 minutes.  Since it only takes about 30 seconds for the thiopental to induce anesthesia, 30-45 seconds for the pancuronium to cause paralysis, and about 30 seconds for the potassium to stop the heart, death can theoretically be attained in as little as 90 seconds. Given that it takes time to administer the drugs through an IV, time for the line to be flushed, time to change the drug being administered, and time to ensure that death has occurred, the whole procedure takes about 7-11 minutes. Procedural aspects in pronouncing death also contribute to delay and, therefore, the condemned is usually pronounced dead within 10 to 20 minutes of starting the drugs. Supporters of the death penalty say that a huge dose of thiopental, which is between 14-20 times the anesthetic induction dose and which has the potential to induce a medical coma lasting 60 hours, could never wear off in only 10 to 20 minutes.
Death penalty supporters state that the claim that pancuronium dilutes the pentothal dose is erroneous. Supporters argue that pancuronium and thiopental are commonly used together in surgery every day and if there were a dilution effect, it would be a known drug interaction.
Drug interactions are a complex topic. Some drug interactions can be simplistically classified as either synergistic or inhibitory interactions. In addition, drug interactions can occur directly at the site of action, through common pathways or indirectly through metabolism of the drug in the liver or through elimination in the kidney. Pancuronium and thiopental have different sites of action, one in the brain and one at the neuromuscular junction. Since the half-life of thiopental is 11.5 hours, the metabolism of the drugs is not an issue when dealing with the short time frame in lethal injections. The only other plausible interpretation would be a direct one, or one in which the two compounds interact with each other. Supporters of the death penalty argue that this theory does not hold true. They state that even if the 100 mg of pancuronium directly prevented 500 mg of thiopental from working, there would be sufficient thiopental to induce coma for 50 hours. In addition, if this interaction did occur, then the pancuronium would be incapable of causing paralysis.
Supporters of the death penalty state that the claim that the pancuronium prevents the thiopental from working, yet is still capable of causing paralysis, is not based on any scientific evidence and is a drug interaction that has never before been documented for any other drugs. Supporters of the death penalty question if this is an invented false claim.
Amnesty International, Human Rights Watch, the Death Penalty Information Center, and other anti-death penalty groups have not proposed a lethal injection protocol which they believe is more humane. Supporters of the death penalty argue that the lack of an alternative proposed protocol is testament to the fact that the humaneness of the lethal injection protocol is not the issue. Instead supporters argue that the issue is the continued existence of the death penalty, since if the only issue was the humaneness of the procedure, then Amnesty International, HRW, or the DPIC should have already proposed a more humane method.
Regardless of an alternative protocol, some death penalty opponents have claimed that execution can be more humane by the administration of a single lethal dose of barbiturate. Supporters of the death penalty, however, state that the single drug theory is flawed concept. Terminally ill patients in Oregon who have requested physician-assisted suicide have received lethal doses of barbiturates. The protocol has been highly effective in producing a humane death, but the time to cause death can be prolonged. Some patients have taken days to die, and a few patients have actually survived the process and have regained consciousness up to three days after taking the lethal dose.  In a Californian legal proceeding addressing the issue of the lethal injection cocktail being "cruel and unusual," state authorities said that the time to death following a single injection of barbiturate is approximately 45 minutes. 
Scientifically this is readily explained. Barbiturate overdoses typically cause death by depression of the respiratory center, but the effect is variable. Some patients may have complete cessation of respiratory drive, whereas others may only have depression of respiratory function. In addition, cardiac activity can last for a long time after cessation of respiration. Since death is pronounced after asystole and given that the expectation is for a rapid death in lethal injection, multiple drugs are required; specifically potassium chloride to stop the heart. In fact, in the case of Clarence Ray Allen a second dose of potassium chloride was required to obtain asystole. The position of death penalty supporters is that death should be obtained in a reasonable amount of time.
Supporters of the death penalty agree that the use of pancuronium bromide is not absolutely necessary in the lethal injection protocol. Some supporters believe that the drug may decrease muscular fasciculations when the potassium is given, but this has yet to be proven.
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