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. It is now the most common form of execution in the United States: every American execution in 2005 was conducted by lethal injection.

Lethal injection has also been used in euthanasia to facilitate voluntary death in patients with terminal or chronically painful conditions. Both applications have used similar drug combinations.

After the condemned is fastened on the execution table, two intravenous cannulae ("IVs") 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. Another line is connected to the drip lines, that is attached to the lethal injection machine in an adjacent room and secured so the line doesn't snap during the injections.

The arm of the subject is swabbed with alcohol before the cannula is inserted.^[9] 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). Finally, it would be a hazard to prison personnel to handle unsterilized equipment. The drips are then started, in both arms and a saline solution is sent flowing through them. This is so the chemicals don't mix and block up the needle making the drugs unable to reach the inmate and not work. A heart monitor is attached so that prison officials can monitor when death has been obtained.

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:

1. Sodium thiopental: to render the offender unconscious.
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: 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 needle, while a second technician, who is usually a member of the prison staff, orders, prepares, and loads the drugs into the lethal injection machine. Two other staff members start the machine up and prepare for the signal to start. 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 lethal injection machine 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

The following drugs are a representation of a typical lethal injection as practiced in the United States for capital punishment.

Sodium thiopental

• 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 [1], 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 [2] 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

• 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.

Other drugs that some other states use are tubocurarine chloride and succinylcholine chloride, both considerably stronger, but most states stick to using Pavulon.

Pancuronium bromide is a derivative of the alkaloid malouetine from the plant Malouetia bequaertiana.

Potassium chloride

• 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. Doctors prescribe potassium for patients 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 stops in systole. 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 protocol

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.