The death penalty once again comes before the US Supreme Court on Wednesday, as the justices take up a case testing whether Oklahoma’s three-drug lethal injection protocol complies with basic constitutional protections against cruel and unusual punishment.

The case does not raise a broad challenge to the constitutionality of capital punishment. Instead, it focuses on one component of a state’s chosen method of carrying out a death sentence.

At issue is whether the first drug in a state’s three-drug procedure is reliably effective in preventing condemned prisoners from suffering an intolerable level of pain during the execution process.

The case is significant because it arises at a time when states are finding it increasingly difficult to purchase drugs for lethal injections in the face of widespread refusal by various companies to sell drugs for capital punishment.

The boycott means that as drugs considered effective for lethal injections are no longer available, states are turning to drugs that are somewhat less effective. The question is, are they effective enough?

A high court decision in the Oklahoma case may offer essential guidance to states struggling to continue to carry out executions without violating safeguards of the Eighth Amendment.

At the center of the case is Oklahoma’s use of the drug midazolam as the first of three drugs administered during an execution.

Lawyers for a group of death row inmates argue that midazolam is not effective in rendering a condemned prisoner into a coma-like state of unconsciousness before the other two drugs are administered.

Medical experts acknowledge that the second and third drugs in the protocol can cause extreme pain. Specialists say it would feel like the equivalent of injecting liquid fire throughout an individual’s system.

The issue of the ineffectiveness of the first drug is being raised after three botched executions in Oklahoma, Ohio, and Arizona. In each case, the prisoner awoke, gasped, and struggled during administration of the other drugs.

In a “humane” execution involving lethal injections, the prisoner is expected to appear to simply fall asleep and remain that way until pronounced dead.

Lawyers for the death row inmates in Oklahoma are urging the high court to declare that the use of midazolam in executions is so risky that it violates the Eighth Amendment.

“A protocol using painful lethal drugs is unconstitutional unless the prisoner is first properly administered a drug that reliably ensures a deep, coma-like unconsciousness throughout the execution,” Robin Konrad, the inmates’ lawyer, wrote in her brief to the court. “Midazolam cannot serve that purpose.”

Ms. Konrad, an assistant federal public defender in Arizona, says there is a medical consensus that midazolam is not capable of generating a deep, coma-like unconsciousness.

The drug has a ceiling effect, in which additional doses do not push the subject into a deeper level of unconsciousness, experts say. In addition, under certain circumstances a subject may be jolted awake by extreme pain, they say.

As such, Konrad argues that the use of midazolam in a lethal injection protocol presents an objectively intolerable risk of harm to the condemned prisoner.

It is a risk, she says, that makes Oklahoma’s lethal injection protocol cruel and unusual.

Oklahoma Solicitor General Patrick Wyrick disagrees with that assessment.

“Oklahoma’s lethal injection protocol does not present a substantial risk of severe pain and cannot be considered cruel,” Mr. Wyrick wrote in his brief to the court.

The solicitor general disputed claims of the existence of a medical consensus about midazolam’s ability to render a subject into a deep coma-like state.

“The record evidence indicates that a large dose of midazolam produces a level of unconsciousness sufficiently deep to render persons insensate to even extremely painful stimuli,” Wyrick said.

The high court dispute over midazolam arises in the context of a broader battle being waged by death penalty opponents.

In recent years, activists have sought to make it increasingly difficult to carry out death sentences, not by convincing state lawmakers to repeal capital punishment, but by making it increasingly difficult for states to obtain the initial drug used in the three-drug lethal injection process.

That drug was sodium thiopental, and later pentobarbital. There is an undisputed medical consensus that both sodium thiopental and pentobarbital can be effective in rendering a condemned inmate into a deep state of unconsciousness.

But those drugs are no longer available to many states for carrying out executions. Drug manufacturers refuse to sell the drug to states seeking to use it for capital punishment. When states attempted to obtain similar drugs from other companies, anti-death penalty activists have pressured those companies to not sell their products for executions as well.

Faced with this shortage, Oklahoma sought to replace pentobarbital with midazolam, even though the two drugs are substantially different and produce different results.

A year ago, in April 2014, Oklahoma sought to execute its first prisoner using the new midazolam-aided protocol. Clayton Lockett was injected with 100 milligrams of midazolam and was declared unconscious after seven minutes.

Then, during administration of the second and third drugs, Mr. Lockett regained consciousness. According to Konrad, he began to writhe against the gurney and buck his head. He also reportedly said that the drugs were messing with his mind, that the drugs weren’t working, and that something was wrong.

Lockett was pronounced dead 24 minutes later.

An investigation concluded that the execution was botched because technicians had failed to properly insert the needle used to deliver the drugs into Lockett’s system.

Konrad says the failure was due to the state’s reliance on midazolam, the same drug used in two other botched executions last year in Ohio and Arizona.

In January 2014, Ohio death row inmate Dennis McGuire gasped for nearly ten minutes until he was pronounced dead.

In July 2014, Arizona death row inmate Joseph Wood gasped and struggled for nearly two hours before being pronounced dead.

Death penalty opponents say the use of midazolam amounts to a form of unregulated experimentation by state corrections departments.

Oklahoma views the dispute in a broader context.

“This case, under the guise of a narrow attack on a single method of execution out of many, is a full-throated attack on the ability of the sovereign states to carry out the death sentences issued by their citizens,” Wyrick said in his brief.

Oklahoma and other states are taking counter-measures.

Last week, Oklahoma Governor Mary Fallin signed into law a new backup procedure that would allow corrections officials to use nitrogen gas in executions if the state’s lethal injection protocol was not available.

The nitrogen gas would be applied through a mask, similar to the use of gas at a dentist’s office. The backup measure becomes available in November.

Oklahoma also retains the electric chair and firing squad as other backup execution methods.

Oklahoma is not the only state to identify backup procedures. Utah selected the firing squad, while Tennessee designated the electric chair.

The case is Glossip v. Gross (14-7955).

A decision is expected by late June.