Pancuronium

Pancuronium bromide is a chemical compound, used in medicine with the brand name Pavulon® (Organon International). It is a muscle relaxant with various purposes. It is one of the drugs administered during a lethal injection.

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Mode of action

Pancuronium is a typical non-depolarising curare-mimetic muscle relaxant. It acts as a competitive acetylcholine antagonist on neuromuscular junctions, displacing acetylcholine (hence competitive) from its post-synaptic nicotinic acetylcholine receptors. It is, unlike suxamethonium, a non-depolarising agent, which means, that it causes no spontaneous depolarisations upon association with the nicotinic receptor in neuromuscular junction, thus producing no muscle fasciculations upon administration. Pancuronium has no hormonal activity. It exerts slight vagolytic activity (i.e. diminishing activity of the vagus nerve) and no ganglioplegic (i.e., blocking ganglions) activity. Pancuronium is a very potent muscle relaxant/curaremimetic, the ED95 (i.e. a dose causing a 95% reduction in muscle activity) being only 60 µg/kg body weight administered intravenously. Usual doses for anesthesiologic muscle relaxation (e.g. for intubation and major surgery) are about 100 µg/kg IV (0.1 mg/kg IV); muscle relaxation suitable for intubation sets in about 90–120 seconds after administration of the drug. Full muscle paralysis for major surgery is achieved about 2–4 minutes post application. Clinical effects (muscle activity lower than 25% of physiological) last for about 100 minutes. The time needed for full (over 90% muscle activity) recovery after single administration is about 120–180 minutes in healthy adults, but can be protracted to more hours in poor health subjects and when concomitantly administered with other long-acting anesthetics (e.g. some opioids, barbiturates, inhalation anesthetics). The effects of pancuronium can be at least partially reversed by anticholinesterasics, such as neostigmine, pyridostigmine and edrophonium.

Uses in medicine

Pancuronium is used with general anaesthesia in surgery for muscle relaxation and as an aid to intubation or ventilation. It does not have sedative or analgesic effects.

Side effects include moderately raised heart rate and thereby arterial pressure and cardiac output, excessive salivation, apnea and respiratory depression, rashes, flushing and sweating. The muscular relaxation can be dangerous in the seriously ill and it can accumulate leading to extended weakness.

In Belgium and the Netherlands, Pancuronium is recommended in the protocol for euthanasia. After administering sodium thiopental to induce coma, Pancuronium is delivered in order to stop breathing.^[1]

A consultant neonatologist, Dr Jeffery Munro, was recently cleared of malpractise by the GMC Fitness to Practise panel after giving 23 times the standard dose of Pancuronium to two neonates. Dr Munro administered 2,000mg of Pancuronium to the babies, who were suffering from Agonal Gasping, after consulting the parents that this would ease pain but hasten death.^[2]

Uses in execution

Procedure

It is also used as one component of a lethal injection used in capital punishment in some parts of the USA. If improperly administered it can cause sodium thiopental, commonly used as the anesthetic in the lethal injection process, to precipitate and become ineffective.^{[citation needed]}

Controversy

Pancuronium bromide has no analgesic effects, and if this precipitation renders the painkiller agent ineffective, an individual could conceivably never achieve unconsciousness, and thus be able to feel all of the pain associated with the procedure, but unable to cry out or move due to the pancuronium's complete paralytic action. There have also been several high-profile civil lawsuits alleging similar failures to achieve analgesia or unconsciousness prior to a general surgical procedures. These too have largely blamed improper or insufficient dosages of painkiller in concert with normal dosages of pancuronium bromide.

Largely echoing this sentiment, Amnesty International has objected to its use in lethal injections on the grounds that it "may mask the condemned prisoner's suffering during the execution"^[3] and thereby lead observers to conclude that lethal injection is painless, or less cruel than other forms of execution.

It wasn't until September 2007 that the US Supreme Court agreed to hear their first case of whether or not the use of lethal injection does in fact violate the US Constitution's Eighth Amendment's ban on cruel and unusual punishment^[4].

Uses in crime

Pavulon® was the compound used in "Angel of Death" Efren Saldivar's killing spree.^[5]

References