For years, doctors, legal scholars, and bioethicists have debated whether lethal injection can ever be a truly reliable or humane method of execution. Those questions came to a boil in early October 2026 after an execution attempt on 50-year-old Christa Pike went wrong at the Riverbend Maximum Security Institution in Nashville, Tennessee. Pike, who was convicted in the 1995 murder of classmate Colleen Slemmer, was given two huge infusions of pentobarbital and lived, reports ABC7 News.
An emergency ambulance took her to a local intensive care unit after executioners were unable to induce cardiac arrest, where she was intubated and put on mechanical ventilation. Her family’s attorney said a week later that she woke up, was taken off the ventilator and could speak from her hospital bed, a medically unheard-of feat in modern American execution history.
Under standard procedures, lethal injection relies on delivering high doses of central nervous system depressants directly into the bloodstream to stop breathing and cause death. When massive amounts of these drugs enter the body, the human system experiences extreme pharmacological toxicity, respiratory failure and widespread chemical tissue damage.
If peripheral intravenous lines blow or extravasate (spill caustic chemical solutions into surrounding subcutaneous muscle tissue without entering the central circulation), the drug cannot reach lethal serum concentrations in the brain. Rather, the patient will have severe localized chemical burns, airway collapse and an emergency critical care admission, mechanical ventilatory support and toxicology clearance to prevent secondary brain injury and systemic organ failure.
What do they use for lethal injection?
Typically, lethal injection methods in the U.S. involve a combination of drugs or a large dose of a central nervous system depressant.
In the past, states used a three-drug cocktail developed in the late 1970s. This protocol was begun with an ultra-short-acting barbiturate for surgical anesthesia (usually sodium thiopental), followed by a paralyzing agent to prevent diaphragmatic breathing (usually pancuronium bromide) and finally a strong solution of potassium chloride to cause myocardial electrical conduction block and cardiac arrest. But as the world’s drug companies declined to export and sell these drugs for correctional executions, corrections departments changed their procedures.
Most of today’s execution states use a one-drug method, a massive overdose of pentobarbital, a potent intermediate-acting oxybarbiturate. Some jurisdictions that have procurement challenges use other sedatives like the benzodiazepine, midazolam, or use a compounded formulation of pentobarbital obtained from a non-federally regulated compounding pharmacy.
The science behind lethal injection drugs
To appreciate the physiology of lethal injection chemicals and the effects of their failure, it is important to look at how the high doses of barbiturates work on cellular neuroreceptors.
According to pharmacology research published by the National Institutes of Health (NIH), pentobarbital selectively binds to gamma-aminobutyric acid type A (GABA_A) receptor complexes throughout the central nervous system. Low doses of barbiturates enhance natural GABA transmission by opening chloride ion channels and hyperpolarizing neuronal membranes, resulting in sedation or sleep under normal clinical anesthesia.
Pentobarbital at the massive, supratherapeutic doses used in an execution (usually 5 grams, which is dozens of times more than a dose used in a clinical anesthetic) directly opens chloride channels, without the use of natural GABA. This results in generalized severe depression of the medullary centers in the brainstem involved with respiration.
All electrical activity responsible for diaphragmatic contraction and involuntary breathing is stopped, and severe acute hypercapnia and profound cellular hypoxia are induced. A decrease in oxygen delivery to the myocardium results in secondary hypoxic arrest and biological death. But this physiological process requires rapid intravenous bioavailability; if the drug does not enter the central circulation quickly enough and at sufficiently high concentrations, the brainstem is only partially suppressed, resulting in unconsciousness and respiratory collapse for a relatively long time without cardiac standstill.
Why safety is a concern
Lethal injection drugs are administered in correctional settings without having the same safety nets, professional ethics and pharmacological oversight that are present in medical settings.
Dr. Justus Rabach, MD, tells Blavity Health, “One of the central paradoxes of lethal injection is that there are major medical organizations, such as the American Medical Association (AMA), the American Nurses Association (ANA), and the American Society of Anesthesiologists (ASA), which prohibit licensed physicians and registered nurses from performing a role in executions. Capital punishment contravenes the fundamental medical principle of ‘do no harm’ contained in the clinical ethics codes. As a result, executions are regularly administered by correctional staff who are not qualified intravenous therapy providers, don’t possess clinical pharmacology training and don’t hold credentials in emergency airway management.”
In addition, state execution departments frequently have very stringent laws that prevent the public from finding out where and how drugs are sourced, when they expire and how they’re made. Commercial drug companies are not willing to provide facilities for executions, so states often call on custom compounding pharmacies to mix pentobarbital. Compounded injectable solutions are not standardized at the federal level and can sometimes become low in active ingredient, have poor pH or contain microparticulate contamination or rapid chemical degradation in a batch. If the chemical is not confirmed to be alkaline and is injected into damaged or fragile peripheral veins, the risk of a procedural catastrophe increases significantly.
Risks and side effects
Surviving or enduring a protracted lethal injection exposes the human body to acute medical complications that range from chemical burning to permanent organ damage.
Severe chemical extravasation and tissue burns
Pentobarbital injectable formulations are chemically prepared at a very high alkaline pH (often 9.5-10.5) to maintain solubility, according to the NIH. When a vein wall is punctured by an IV or if the IV becomes dislodged, the highly basic IV solution enters the surrounding soft tissues. This chemical extravasation results in instant liquefactive tissue necrosis, extensive chemical burns to the skin, blisters and possible compartment syndrome, all of which were reported in Pike when she was hospitalized after her execution.
Acute pulmonary edema and chemical suffocation
As explained by NPR, autopsy findings show that high-dose pentobarbital injection often causes worsening acute pulmonary edema before the loss of consciousness. Alveolar capillaries leak fluid and blood directly into the lungs, resulting in a “chemical drowning” or “acute asphyxiation” feeling, and the person cannot communicate their distress.
Hypoxic ischemic encephalopathy
In the case of breathing failure but not cardiac arrest, as critical care researchers emphasize, brain tissue is deprived of oxygen for long periods. This cerebral hypoxia may result in permanent hypoxic ischemic encephalopathy that can cause cognitive impairments, memory loss, motor deficits and post-anoxic seizure disorders.
Is Christa Pike on a ventilator?
According to statements from her legal defense, Christa Pike is now off a mechanical ventilator.
Emergency medical staff rushed Pike from the prison to the intensive care unit at a Nashville hospital, where she was immediately intubated and placed on mechanical life support to treat her severe respiratory depression and to remove the large amount of chemicals from her system after a failed execution attempt on Sept. 30.
Her lawyers said her clinical condition improved to the point that a week after the incident, it was safe to remove the endotracheal tube. She is now alert and can talk, but medical authorities stress that she is still in intensive care, being closely monitored for delayed chemical poisoning and for secondary infections and tissue necrosis in her arms.
Who is not a candidate for lethal injection?
From a medical and legal standpoint, lethal injection procedures pose catastrophic physiological risks for persons with certain vascular, metabolic and neurological vulnerabilities.
Clinical assessment data from the American Society of Anesthesiologists (ASA) indicate that patients with severe peripheral vascular disease, chronic venous insufficiency or a history of long-term IV access problems are at extreme risk for blowouts, infiltration and painful chemical extravasation during cutdown or peripheral catheterization procedures.
In addition, medical toxicology experts note that those with impaired renal or hepatocellular excretion pathways are unable to metabolize or eliminate large barbiturate overdoses and will instead experience unpredictable, prolonged (multi-day) comas instead of hasty cessation of vital functions.
Furthermore, in those who have extreme respiratory compromise, such as in advanced chronic obstructive pulmonary disease (COPD) or restrictive lung disease, there is collapse of the pulmonary capillaries and severe dyspnea during sub-lethal delivery of sedatives.
Clinical best practices for critical poisoning
In clinical practice, if someone has a large amount of barbiturate toxicity or if the drug is extruded from a vein into the surrounding tissues, special emergency medical procedures are used to prevent death by respiratory arrest or loss of soft tissue viability.
Advanced airway management and mechanical ventilation
There is no specific pharmacologic reversal agent or antagonist (such as naloxone for opioids or flumazenil for benzodiazepines), so medical teams must secure the patient’s airway with endotracheal intubation. Mechanical ventilators provide positive-pressure oxygenation to correct blood gas imbalance and prevent brain hypoxia (deficiency of oxygen to the brain); the liver and kidneys will gradually remove the drug from the bloodstream.
Urinary alkalinization and hemoperfusion
In the setting of severe barbiturate overdose, clinical toxicologists use intravenous sodium bicarbonate infusion to alkalinize the urine to a pH of 7.5–8.0, thereby converting weak barbiturate acids into ionized forms that cannot be reabsorbed by the renal tubules and facilitating urinary clearance. If it is a life-threatening situation with refractory shock, emergency charcoal hemoperfusion or continuous renal replacement therapy (hemodialysis) is started to remove the drug directly from the circulation.
Extravasation antidote infiltration
Leaks of caustic, alkaline solutions into arm tissues are addressed by critical care teams with immediate aspiration of fluids via the catheter to remove as much fluid as possible before removal. Affected limb is elevated, hot and cold compresses are applied alternately, and subcutaneous injection of antidotes such as hyaluronidase or phentolamine may be made in the area to disperse the chemical and prevent more extensive sloughing and necrosis of the skin.
“The person would feel either asphyxiation or the burning sensation associated with the potassium,” said Dr. Leonidas Koniaris, a surgeon and co-author at the University of Miami. “The potassium would cause extreme discomfort, something like being put on fire.”
Bottom line
Tennessee death row inmate Christa Pike’s survival after two doses of pentobarbital is unprecedented, and it has exposed the serious physiological harm, absence of clinical protections and pharmacological challenges of lethal injection. High-dose barbiturates are intended to produce brainstem depression and stop breathing, but if they are poorly administered intravenously, they can cause devastating chemical burns to soft tissues, acute pulmonary edema and prolonged cerebral hypoxia without death from cardiac arrest. Intensive care and mechanical ventilation allowed Pike to wake up after the execution attempt, but surviving an attempted execution leaves heavy physical and neurological damage that requires extensive critical care management.
Frequently Asked Questions
How long is the last meal before execution?
In most correctional jurisdictions across the United States, an inmate is served their requested last meal between two and four hours before the scheduled execution time to minimize the risk of vomiting and pulmonary aspiration during the procedure.
Can someone be revived after a lethal injection?
While exceptionally rare in correctional history, a person can be medically revived following an incomplete or failed lethal injection if emergency first responders immediately initiate endotracheal intubation, continuous mechanical ventilation and cardiovascular hemodynamic support before irreversible, fatal brain death occurs.
Citations
ABC7 News. Christa Pike is conscious and speaking after Tennessee failed execution, her attorneys say. ABC7 San Francisco. October 6, 2026. https://abc7news.com/story/christa-pike-is-conscious-speaking-tennessee-failed-execution-attorneys-say/19914643/
Muroi Y, Theusch CM, Czajkowski C, Jackson MB. Distinct structural changes in the GABAA receptor elicited by pentobarbital and GABA. Biophys J. 2009;96(2):499-509. doi:10.1016/j.bpj.2008.09.037
Dohi M, Ueda K, Yamagiwa Y, Yamashita A, Sakamoto Y. Stability of Sodium Pentobarbital Aqueous Solution During Short‐Term Chilled and Ambient‐Temperature Storage. Veterinary Medicine and Science. 2024;10(6). doi:10.1002/vms3.70066
Caldwell N, Chang A, Myers J. Gasping for Air: Autopsies Reveal Troubling Effects of Lethal Injection. NPR. September 21, 2020. https://www.npr.org/2020/09/21/793177589/gasping-for-air-autopsies-reveal-troubling-effects-of-lethal-injection
Johnston AJ, Simpson MJ, McCormack V, et al. Association of Anaesthetists guidelines: safe vascular access 2025. Anaesthesia. 2025;80(11):1381-1396. doi:10.1111/anae.16727