April 22, 2015
Private: Supreme Court: Base Lethal Injection Decisions on Science
by Ellen M. Unterwald, Ph.D., Professor of Pharmacology, and Director, Center for Substance Abuse Research, Temple University School of Medicine
Imagine a hospital administering a drug protocol devised without consideration of its scientific properties, selected by individuals without medical training. It’s unthinkable, but in the state of Oklahoma, prison officials without any pharmaceutical or medical training selected a combination of drugs to cause death. They elected to use midazolam as the first drug in the state’s three-drug lethal injection protocol despite the fact that there is overwhelming scientific consensus, including among pharmacologists like myself, that midazolam is incapable of inducing a deep, coma-like unconsciousness characteristic of general anesthesia and required for a humane and constitutional execution.
The upcoming U.S. Supreme Court case, Glossip v. Gross, addresses the use of midazolam in lethal injection executions. As a pharmacologist who studies drugs, I strongly believe the Supreme Court should prevent Oklahoma from using midazolam in lethal injection executions, and encourage states to base lethal injection protocols on all available scientific knowledge and research.
The function of the first drug in Oklahoma’s three-drug lethal injection protocol is to ensure a prisoner is in a deep, coma-like unconsciousness prior to the injection of a paralytic agent to stop respiration and a third drug to induce cardiac arrest. Yet Oklahoma’s choice to use midazolam runs counter to the way that pharmacologists recognize that the drug works and counter to the way midazolam is used in the clinical setting by doctors. Glossip v. Gross will examine the constitutionality of this practice.
It is essential that scientific principles guide decisions about the drugs used for lethal injections. From a pharmacological perspective, midazolam is incapable of producing the state of general anesthesia characterized by unconsciousness and inability to feel pain. Midazolam is a member of the benzodiazepine family, a class of drugs that also includes the active pharmaceutical ingredients in Xanax® and Valium®.
Benzodiazepines are central nervous system depressants that reliably provide sedative, hypnotic, muscle relaxant, antianxiety, and anticonvulsant effects. But it is widely recognized in the scientific and medical community that midazolam alone cannot be used to maintain adequate anesthesia for surgery.
The biochemical mechanism by which midazolam produces its pharmacological effects on the human body induces only short-term, shallow central nervous system depression. In clinical practice, midazolam is often used as a pre-medication prior to the administration of an anesthetic agent. Midazolam relaxes a patient, relieves anxiety, and induces drowsiness prior to the administration of a different drug that achieves the deep unconsciousness of anesthesia. But midazolam alone cannot produce and maintain general anesthesia, even at an excessive dose. The reason for this is referred to as the “ceiling effect” of the benzodiazepine response. As the dose of benzodiazepine increases, the biological response to the drug reaches a plateau or “ceiling” before general anesthesia can be obtained. Increasing the dose of the benzodiazepine beyond this plateau will not increase its effectiveness as an anesthetic agent.
Midazolam is therefore unlike drugs in the barbiturate class, which offer a greater depth of unconsciousness. Barbiturates are not limited by a ceiling effect, so greater doses provide a greater biological response, reliably producing anesthesia, coma, and death. The reason that benzodiazepines like midazolam will not produce greater pharmacological effects is two-fold. First, to exert a pharmacological effect, benzodiazepines require the presence in the body of a naturally occurring neurotransmitter, GABA. In the body, this neurotransmitter is present in limited supply, which consequently restricts the pharmacological effect of benzodiazepines. Barbiturates, on the other hand, do not require the presence of a neurotransmitter in the body to produce a biological effect. Second, while increased doses of barbiturates completely shut down the activity of nerve cells in the body, benzodiazepines merely decrease nerve activity for short periods of time.
For these reasons, midazolam cannot provide relaxation sufficient to allow surgery. Awareness persists, and painful stimuli can break through the relaxed state. In the context of Oklahoma’s lethal injection drug protocol, the administration of the second and third drugs—a paralytic to stop respiration, followed by potassium chloride to induce cardiac arrest—would be expected to jolt a person from the midazolam-induced relaxed state.
Pharmacologists, whose field of study is the actions of drugs on the body, readily recognize that midazolam is not appropriate for its intended purpose under Oklahoma’s lethal injection protocol. In the clinical setting, midazolam is not used as a stand-alone anesthetic. The upcoming Glossip v. Gross case before the Supreme Court shows why it is essential that scientific knowledge about drugs be brought to bear on lethal injection decisions.