The History of Opioid Use in Anesthetic Delivery

Stanley, Theodore H.

doi:10.1007/978-1-4614-8441-7_48

Cited by 10 publications

(21 citation statements)

References 115 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Fentanyl effectively replaced morphine in major surgery due to its significantly greater potency and hemodynamic stability compared with high-dose morphine. Although fentanyl has not replaced morphine-derived alkaloids, F/FAs have become some of the world's most important and frequently used opioid analgesics (Stanley, 2014).…”

Section: Fentanyl Pharmacology and Pharmacokineticsmentioning

confidence: 99%

“…Fentanyl (Sublimaze), and its analogs (F/FA) were the cause of death in .50% of United States deaths related to opioids in 2016 and estimated to be .70% for 2017 and 2018 (Hedegaard et al, 2018;Jannetto et al, 2019); data are from the Centers for Disease Control. action and peak plasma concentrations are dependent on the dosage, method of delivery, and rapidity of injection; however, profound analgesic effects consistently appear within 90-120 seconds after intravenous administration and with plasma concentrations as low as 0.2-1.2 ng/ml in both opioid-naive and opioid-tolerant patients (Grell et al, 1970;Stanley, 2014).…”

Section: Fentanyl Pharmacology and Pharmacokineticsmentioning

confidence: 99%

“…WCS has occasionally been encountered following as little as 50 mg fentanyl given intravenously, can emerge in less than 2 minutes, last up to 15 minutes, and appears to cause death with a more accelerated time course than respiratory depression (Grell et al, 1970;Bailey et al, 1988;Stanley, 2014;Burns et al, 2016). It is important to note that WCS at low doses or doses given regularly in procedural sedation (,100 mg or 0.5-1 mg/kg) is extremely uncommon.…”

Section: Fentanyl Pharmacology and Pharmacokineticsmentioning

confidence: 99%

“…Belgian chemist Paul Janssen first synthesized the fully synthetic opioid, fentanyl, in 1960, which revolutionized the field of surgical anesthesia. Fentanyl has extremely high potency (e.g., ∼150 greater than morphine) and hemodynamic stability (Stanley, 2014). Like all narcotics given in sufficient quantity, fentanyl/fentanyl analogs (F/FAs) can induce dose-dependent respiratory depression, hypoxia, and death (Stanley, 2014).…”

Section: Introductionmentioning

confidence: 99%

“…Fentanyl has extremely high potency (e.g., ∼150 greater than morphine) and hemodynamic stability (Stanley, 2014). Like all narcotics given in sufficient quantity, fentanyl/fentanyl analogs (F/FAs) can induce dose-dependent respiratory depression, hypoxia, and death (Stanley, 2014). Unlike morphine-derived alkaloids, F/FAs can rapidly induce a combination of vocal cord closure (laryngospasm) and severe muscle rigidity in the chest wall and diaphragm at doses well within therapeutic ranges used The contents do not represent the views of the US Department of Veterans Affairs or the United States Government.…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

Noradrenergic Mechanisms in Fentanyl-Mediated Rapid Death Explain Failure of Naloxone in the Opioid Crisis

Torralva

Janowsky

2019

J Pharmacol Exp Ther

112

View full text Add to dashboard Cite

In December 2018, the Centers for Disease Control declared fentanyl the deadliest drug in America. Opioid overdose is the single greatest cause of death in the United States adult population (ages 18-50), and fentanyl and its analogs [fentanyl/ fentanyl analogs (F/FAs)] are currently involved in .50% of these deaths. Anesthesiologists in the United States were introduced to fentanyl in the early 1970s when it revolutionized surgical anesthesia by combining profound analgesia with hemodynamic stability. However, they quickly had to master its unique side effect. F/FAs can produce profound rigidity in the diaphragm, chest wall and upper airway within an extremely narrow dosing range. This clinical effect was called wooden chest syndrome (WCS) by anesthesiologists and is not commonly known outside of anesthesiology or to clinicians or researchers in addiction research/medicine. WCS is almost routinely fatal without expert airway management. This review provides relevant clinical human pharmacology and animal data demonstrating that the significant increase in the number of F/FA-induced deaths may involve a-adrenergic and cholinergic receptor-mediated mechanical failure of the respiratory and cardiovascular systems with rapid development of rigidity and airway closure. Although morphine and its prodrug, heroin, can cause mild rigidity in abdominal muscles at high doses, neither presents with the distinct and rapid respiratory failure seen with F/FA-induced WCS, separating F/FA overdose from the slower onset of respiratory depression caused by morphine-derived alkaloids. This distinction has significant consequences for the design and implementation of new pharmacologic strategies to effectively prevent F/FA-induced death. SIGNIFICANCE STATEMENT Deaths from fentanyl and F/FAs are increasing in spite of availability and awareness of the opioid reversal drug naloxone. This article reviews literature suggesting that naloxone may be ineffective against centrally mediated noradrenergic and cholinergic effects of F/FAs, which clinically manifest as severe muscle rigidity and airway compromise (e.g., wooden chest syndrome) that is rapid and distinct from respiratory depression seen with morphine-derived alkaloids. A physiologic model is proposed and implications for new drug development and treatment are discussed.

show abstract

Section: Fentanyl Pharmacology and Pharmacokineticsmentioning

confidence: 99%

Section: Fentanyl Pharmacology and Pharmacokineticsmentioning

confidence: 99%

Section: Fentanyl Pharmacology and Pharmacokineticsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Noradrenergic Mechanisms in Fentanyl-Mediated Rapid Death Explain Failure of Naloxone in the Opioid Crisis

Torralva

Janowsky

2019

J Pharmacol Exp Ther

112

View full text Add to dashboard Cite

show abstract

Analgesic and Anesthetic Amides

Erhard

2016

Bioactive Carboxylic Compound Classes: Pharmaceuticals and Agrochemicals

View full text Add to dashboard Cite

Cytotoxic effects of psychoactive isobutyrylfentanyl and its halogenated derivatives on isolated rat hepatocytes

Nakagawa

Suzuki

et al. 2023

J of Applied Toxicology

View full text Add to dashboard Cite

The novel and numerous psychoactive compounds derived from the analgesic prescription drug N‐phenyl‐N‐[1‐(2‐phenylethyl)piperidin‐4‐yl]propanamide (fentanyl) have been illegally abused as recreational drugs and caused numerous fatalities. Because some psychoactive/psychotropic drugs are known to be hepatotoxic in humans and experimental animals, the cytotoxic effects and mechanisms of 4‐fluoroisobutyrylfentanyl (4F‐iBF), 4‐chloroisobutyrylfentanyl (4Cl‐iBF), and the parent compound isobutyrylfentanyl (iBF) were studied in freshly isolated rat hepatocytes. 4F‐iBF caused not only concentration (0–2.0 mM)‐ and time (0–3 h)‐dependent cell death accompanied by the depletion of cellular ATP and reduced glutathione (GSH) and protein thiol levels but also the accumulation of oxidized glutathione. Of these fentanyls examined, 4Cl‐iBF/4F‐iBF‐induced cytotoxicity with the loss of mitochondrial membrane potential at concentrations of 0.5 and 1.0 mM and the production of reactive oxygen species (ROS) at 0.5 mM were greater than those induced by iBF. The pretreatment of hepatocytes with N‐acetyl‐l‐cysteine as a precursor of cellular GSH ameliorated, at least in part, cytotoxicity accompanied by insufficient ATP levels, the loss of mitochondrial membrane potential, and generation of ROS caused by 4Cl‐iBF/4F‐iBF, whereas pretreatment with diethyl maleate as a GSH depletor enhanced fentanyl‐induced cytotoxicity accompanied by the rapid loss of cellular GSH. Taken collectively, these results indicate that the onset of cytotoxic effects caused by these fentanyls is partially attributable to cellular energy stress as well as oxidative stress.

show abstract

The History of Opioid Use in Anesthetic Delivery

Cited by 10 publications

References 115 publications

Noradrenergic Mechanisms in Fentanyl-Mediated Rapid Death Explain Failure of Naloxone in the Opioid Crisis

Noradrenergic Mechanisms in Fentanyl-Mediated Rapid Death Explain Failure of Naloxone in the Opioid Crisis

Analgesic and Anesthetic Amides

Cytotoxic effects of psychoactive isobutyrylfentanyl and its halogenated derivatives on isolated rat hepatocytes

Contact Info

Product

Resources

About