In 1977, Jay Chapman, Oklahoma's state medical examiner, proposed a new, 'more humane' method of execution: "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.""So Long as They Die: Lethal Injections in the United States," Human Rights Watch, 2006, 18(1). I. Development of Lethal Injection Protocols. After being approved by anesthesiologist Stanley Deutsch, the method was adopted by Oklahoma (Title 22, Section 1014(A)). Since then, thirty-seven of the thirty-eight states using capital punishment have introduced lethal injection statutes. On 7 December 1982, Texas became the first state to use lethal injection as a capital punishment for the execution of Charles Brooks, Jr..Groner, Jonathan I. (2002) "Lethal injection: a stain on the face of medicine," BMJ, 325, 1026-1028. Nazi Germany's T-4 Euthanasia Program also used lethal injection to destroy 'life unworthy of life.'

China began using this method in 1997, Guatemala in 1998, and the Philippines in 1999; multiple other countries have also legally, but not practically adopted the method.

Procedure

After the condemned is fastened on the execution table, two intravenous catheters are inserted, one in each arm. Only one is used for the execution, the other is reserved as a backup in case the primary IV fails.

The arm of the condemned is swabbed with alcohol before the needle is inserted. Along with its antiseptic use, the alcohol also causes the blood vessels to rise to the skin's surface, making it easier to insert the needle. ^* The needles and equipment used are also sterilized. One reason for this is because the needles are standard medical products that are sterilized during manufacturing. Also, there is a chance that the prisoner could receive a stay of execution after the needles have been inserted as happened in the case of James Autry in October 1983 (he was executed eventually on 14 March 1984). Finally, it would also be a hazard for those handling unsterile equipment.

The intravenous injection is usually a mixture of compounds, designed to induce rapid unconsciousness followed by death through paralysis of respiratory muscles and/or by inducing cardiac hyperpolarization. The execution of the condemned in most states involves three separate injections:

1. Sodium thiopental: to induce a state of unconsciousness intended to last while the other two injections take effect.
2. 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.
3. Potassium chloride: to stop the heart from beating, and thus cause death: see cardiac arrest.

The intravenous tubing leads to a room next to the execution chamber, usually separated from the inmate by a curtain or wall. Usually some type of IV technician with certification to insert the IV performs that role, while the chemical technician, who is usually a member of the prison staff, orders, prepares, and loads the chemicals into the machine. 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 machine which mechanically delivers the three drugs in sequence. During the execution, the patient's cardiac rhythm is monitored and death is pronounced after cardiac activity stops. Death usually occurs within seven minutes, although the whole procedure can take up to 45 minutes. 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

Sodium thiopental

Sodium thiopental (US trade name: Pentothal) is an ultra-short acting barbiturate, often used for anesthesia induction and for medical induced comas. 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 patient 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.

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 stays 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 comas.

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, includes profound respiratory depression (depression of the brainstem respiratory center) and vascular collapse (vasodilatation and myocardial depression), which is in itself lethal.

Thiopental historically has been one of the most common used and studied drugs for the induction of comas. 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.

Pancuronium bromide

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 0.1 mg/kg (a person who weighs 200 pounds, or 91 kilograms, would get a dose of around 9mg). With a 100 milligram dose, the onset to 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. ^*

Potassium chloride

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 activity of the heart muscle to be lower than normal.

Making the resting potential even lower slows conduction and reduces the ability of the muscle to depolarize and contract. 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 stops 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 go from a normal state to death within seconds.

Euthanasia protocol

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 dichloride (Alloferin) or 18 mg pancuronium dibromide (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 (Nesdonal) 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 dibromide (Pavulon) or 20 mg vecuronium bromide (Norcuron). The muscle relaxant should preferably be given intravenously, in order to ensure optimal availability. Only for pancuronium dibromide (Pavulon) are there substantial indications that the agent may also be given intramuscularly in a dosage of 40 mg.^*

Constitutionality in the United States

Ethics of lethal injection

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

Awareness

Opponents point to the fact that sodium thiopental is typically used as an induction agent and not used in the maintence phase of surgery because of its short acting nature. Following the administration of thiopental, pancuronium bromide, is given, to which opponents argue that it not only dilutes the thiopental, but masks any pain when the thiopental wears off since the patient is paralyzed.

Opponents argue that the method of administration is also flawed. They state that since the personnel administering the lethal injection lack expertise in anesthesia and, as such, 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 pacuronium 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 and the inmate is physically restrained. Critics believe, therefore, that the administration of pancuronium serves no purpose other than to create the appearance of a serene death rather than to actually provide a humane death.

Research

Single drug

Cruel and unusual

Controversy: Arguments in support

Commonality

Anesthesia awareness

Anesthesia awareness occurs when there is inadequate inhaled anesthetics given by the anesthesiologist. Barbiturates are only given during the induction phase of anesthesia and these medications rapidly and reliably induce anesthesia. A depolarizing paralytic or a nondepolarizing paralytic, like pancuronium, may then be given to cause paralysis which facilitates intubation. Once intubation has been attained, the anesthesia is converted to the inhaled anesthetics since the barbiturates at the dose given induce unconsciousness for only 5-20 minutes. The anesthesiologist has the responsibility to ensure that the inhaled anesthetics are started soon after intubation to prevent the patient from waking up.

Anesthesia is not maintained with the barbiturate class of drugs since these drugs have extremely long half-lives. The "ultra-short" acting pentothal has a half-life of approximately 11.5 hours and the long acting phenobarbital has a half-life of approximately 4-5 days. In contrast, the inhaled anesthetics have extremely short half-lives and allow the patient to wake up from surgery. If the barbiturate class of drugs was used for anesthesia, patients would not wake up for days. Patients only regain consciousness if the anesthesiologist fails to give sufficient inhaled anesthetics. Therefore, anesthesia awareness is not a problem when dealing with the barbiturate class of drugs, it only occurs if there is inadequate inhaled anesthetics.

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 pentothal 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 adds time and, therefore, the condemned is usually pronounced within 10 to 20 minutes of starting the drugs. Supporters of the death penalty say that a megadose of pentothal, which is anywhere from 14-20 times the normal dose and one in which a medical coma is induced for about 60 hours, is impossible to wear off in 10 to 20 minutes.

Dilution effect

Drug interactions are a complex topic, but most 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 pentothal have completely different sites of action, one in the brain and one at the neuromuscular junction. Since the half-life of pentothal is on the order of hours, the metabolism of the drugs it is a nonissue when dealing with the short time frame in lethal injection. 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 pentothal from working, there would be enough pentothal 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 pentothal from working yet still is 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.

Blood levels

The barbiturate class of drugs is highly lipophilic, meaning that the drugs are absorbed and reach high concentration in fatty tissues. Measurement of the drug by blood testing after administration is difficult to assess since most of the drug will not be in the blood. Blood levels soon after administration are the highest for the barbiturate class since the drug has not completely cleared from the blood. This is known as the initial volume of distribution. After a short period of time, the drug then reaches its apparent volume of distribution. Pentothal's initial volume of distribution is 13.8 liters and its apparent volume of distribution is 233 liters.^* Essentially, any blood level drawn after an execution could be compared to the drug level that one would expect in the initial distribution. Since the apparent volume of distribution is much larger than the initial distribution, and hence its blood concentration much lower, any researcher can incorrectly claim that the level of pentothal was insufficient.

Given that the half-life of pentothal is 11.5 hours, the amount of pentothal required in the brain to induce anesthesia is about 50-75 milligrams, and that the dose of pentothal given is 5 grams, supporters of the death penalty state that common sense and medical experience indicate that the condemned is in a coma with certainty. Supporters of the death penalty therefore argue that the conclusions derived from the research must be politically motivated.

In fact, the researchers state that “participation of doctors in protocol design and execution is ethically prohibited.”Therefore, the authors conclude that "a more effective, humane protocol cannot be developed."[http://www.thelancet.com/journals/lancet/article/PIIS0140673605663453/fulltext?pubType=related Supporters of the death penalty state that the bias of the authors and faulty study design invalidates the study's conclusions.

Single drug

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 attaining a humane death, but the onset to actual death can be a drawn out process. Some patients have taken days to die whereas 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 if the lethal injection cocktail was "cruel and unusual," State authorities said that the time to death following a single injection of barbiturate is approximately 45 minutes.[http://www.latimes.com/news/local/la-me-morales15feb15,1,524324.story?page=2

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, potentially hours, 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 attain asystole. The position of death penalty supporters is that death should be attained 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 fasiculations when the potassium is given, but this has yet to be proven. Irrespective, supporters argue that the dose of thiopental is so high that the condemned will be in stage 4 anesthesia theoretically for over 2 days and that there is zero risk to consciouness being regained.

See also

• Capital punishment in the United States
• Euthanasia

References