The peripherally acting skeletal muscle relaxants (more correctly named neuromuscular blocking agents [NMBAs]), characteristically interfere with the transmission of impulses from motor nerves to skeletal muscle fibers at the neuromuscular junction, thus decreasing or abolishing motor activity.
The skeletal muscle paralysis produced by NMBAs is not associated with depression of the CNS. Animals are fully conscious throughout the period of immobilization, unless an anesthetic or hypnotic agent is administered concurrently.
Neuromuscular transmission can be modified either at the axonal membrane (prejunctional blockade) or at the cholinergic nicotinic receptors in the sarcolemma (postjunctional blockade).
Before neuromuscular blockade is initiated, all other medications used on the patient should be reviewed, because several agents can potentiate the activity of nondepolarizing NMBAs. These agents include inhalant anesthetics (isoflurane and sevoflurane), some antimicrobials, and various other drugs (quinidine, procaine, lidocaine, diazepam, and barbiturates).
Aminoglycosides (eg, gentamicin), polymyxins, tetracyclines, and lincosamides appear to amplify the NMBA activity by decreasing the availability of Ca2+ at membrane-binding sites on the axonal terminal and/or by decreasing the sensitivity of nicotinic receptors to acetylcholine (ACh).
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Local anesthetics also can interact with NMBAs and affect neuromuscular transmission. In high concentration, these anesthetics can stabilize membranes by blocking both Na+ and K+ channels; hemicholinium can inhibit the synthesis of ACh by blocking choline uptake into the nerve.
NMBAs are either depolarizing (eg, succinylcholine) or nondepolarizing (eg, atracurium). NMBAs that are used to induce neuromuscular blockade must be chosen carefully, taking into account clinical indications, patient factors, and the procedure being performed.
Competitive Nondepolarizing Neuromuscular Blocking Agents
Competitive nondepolarizing NMBAs are a group of peripherally acting skeletal muscle relaxants often referred to as curarizing agents because of their relationships with the curare alkaloids that were the first such drugs to be used clinically.
Nondepolarizing NMBAs are competitive ACh antagonists that bind directly to postsynaptic nicotinic receptors. This direct binding prevents ACh from binding to the receptor and prevents the motor end plate from depolarizing, resulting in skeletal muscle paralysis.
Nondepolarizing NMBAs have no effects on smooth and cardiac muscles. On the basis of their chemical structure, competitive nondepolarizing NMBAs are classified as either steroidal (eg, rocuronium, vecuronium, pancuronium) or benzylisoquinolinium (eg, atracurium, cisatracurium). However, all agents share the same mechanism of action and main effect. They differ in their metabolism and some adverse effects.
NMBAs produce complete paralysis of skeletal muscles, without CNS depression; in other words, they provide no sedation or analgesia. All skeletal muscles, including those responsible for ventilation and protective reflexes, are paralyzed. Consequently, NMBAs are used only in the context of general anesthesia, where CNS depression is provided by other means, and mechanical ventilation is also instituted. Administering NMBAs to conscious animals is considered inhumane.
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Generally, nondepolarizing muscle relaxants are not absorbed from the GI tract and must be administered parenterally, almost exclusively intravenously during general anesthesia. Plasma-protein binding is minimal, and there is rapid equilibration, but only within the extracellular fluid. The blood-brain and blood-placenta barriers are rarely crossed. Therefore, NMBAs can be used safely in pregnant animals; they can be administered during cesarean sections to provide muscular relaxation without affecting the fetus.
NMBAs undergo metabolic transformation to some extent, and the metabolites are excreted by both renal and biliary routes in most instances. In general, steroidal compounds undergo organ metabolism (renal or hepatic); therefore, decreased function of these systems, or decreased cardiac output, can delay their transformation and increase their duration of action.
Benzylisoquinolinium drugs undergo biotransformation that does not rely on organ function, such as enzymatic hydrolysis and Hofmann elimination (a process of spontaneous degradation that occurs at normal pH and temperature). As a consequence, the elimination of this class of NMBAs and their duration of action are less affected by changes in organ function. The elimination half-lives of benzylisoquinoliniums at standard dosages are 60–100 minutes, and paralysis typically lasts 20–60 minutes, depending on the agent, the dose, and the rate of biotransformation.
After IV administration of competitive nondepolarizing NMBAs, the skeletal muscles become totally flaccid and nonresponsive to neuronal stimulation. Muscles capable of rapid movement, such as those of the eye, are paralyzed before the larger muscles of the head and neck, which are followed by those of the limbs and body. Finally, the diaphragm becomes paralyzed, and respiration ceases.
As long as ventilation is controlled (via tracheal intubation and positive-pressure ventilation), nondepolarizing NMBAs have virtually no adverse effects, and full recovery ensues in reverse order, with the diaphragm regaining function first. However, return of diaphragmatic activity, and even adequate spontaneous ventilation, does not necessarily mean that all other muscles (eg, and importantly, the laryngeal muscles and swallowing integrity) have regained their function.
All currently used nondepolarizing NMBAs have mild cardiovascular effects, many of which are mediated by autonomic and histaminic receptors. Pancuronium causes a moderate increase in heart rate and, to a lesser extent, in cardiac output. The cardiovascular effects of the other steroidal agents—rocuronium and vecuronium—are typically considered negligible; however, mild changes in heart rate might be observed.
Benzylisoquinolinium compounds are prone to induce histamine release when large doses are used. This effect, which can happen with atracurium, is minimized with cisatracurium.
Several metabolic derangements, such as hyper- and hypomagnesemia, hypokalemia, acidosis, and hypothermia, also prolong the action of nondepolarizing NMBAs. Animals with myasthenia gravis are much more susceptible to the action of muscle relaxants.
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There are multiple indications for the use of nondepolarizing NMBAs:
muscle relaxation for surgery, in particular for intraocular procedures
asynchrony during mechanical ventilation
tracheal intubation (infrequently in veterinary species)
balanced anesthesia
cesarean section in toxic or high-risk animals
epileptiform seizures not controllable with usual anticonvulsant agents
Because NMBAs produce paralysis without CNS depression, these indications are constrained to anesthetized and mechanically ventilated patients. Vital functions and depth of anesthesia in these patients should be carefully monitored, with the understanding that some commonly used indicators of anesthetic depth, such as eye position, jaw tone, and palpebral reflexes, will be abolished.
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Ensuring the restoration of neuromuscular function is imperative at the time of tracheal extubation and recovery from anesthesia. Residual neuromuscular blockade can contribute to decreased ventilation and obtunded protective reflexes, such as swallowing, and can increase the risk of postanesthetic complications, such as hypoxia, hyperventilation, and aspiration.
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Neuromuscular blockade can be reversed spontaneously as the agents undergo biotransformation, or it can be enhanced or accelerated, which is often necessary before emergence from general anesthesia. Two mechanisms can reverse neuromuscular blockade: an indirect mechanism using acetylcholinesterase inhibitors, and a direct mechanism using the selective relaxant binding agent sugammadex.
The dosages provided in the table are only general guidelines for the use of competitive NMBAs.
Competitive Nondepolarizing Agents and Antagonists
Drug | Dosage |
|---|---|
Nondepolarizing Agents | |
Atracurium | Dogs: 0.2–0.5 mg/kg, IV as bolus; 4–9 mcg/kg/min, IV as CRI1,2 Cats: 0.2 mg/kg, IV3 Horses: 0.1–0.2 mg/kg, IV as bolus; 0.2 mg/kg/h, IV as CRI4 |
Cisatracurium | Dogs and cats: 0.1–0.15 mg/kg, IV5,6 Horses: 0.05–0.1 mg/kg, IV7 |
Rocuronium | Dogs: 0.4–0.6 mg/kg, IV8,9 Cats: 0.3–0.6 mg/kg, IV10,11 Horses: 0.2–0.4 mg/kg, IV12 |
Vecuronium | Dogs: 0.05–0.1 mg/kg, IV13 Cats: 0.05–0.1 mg/kg, IV14 |
Antagonists | |
Edrophonium | Dogs and cats: 0.1–0.5 mg/kg, IV; may be combined with an anticholinergic (atropine at 0.02–0.04 mg/kg, IV, or glycopyrrolate at 0.01 mg/kg, IV) to avoid muscarinic effects15 Horses: 0.1–0.5 mg/kg, IV slowly over 1–2 min; the infusion should be stopped or an anticholinergic administered (atropine at 0.02–0.04 mg/kg, IV) if the horse develops bradycardia or hypotension during administration15 |
Neostigmine | Dogs and cats: 0.02–0.04 mg/kg, IV, combined with or preceded by an anticholinergic (atropine at 0.02–0.04 mg/kg, IV, or glycopyrrolate at 0.01 mg/kg, IV) to avoid muscarinic effects15 |
Sugammadex | Dogs and cats: 1.0–4.0 mg/kg, IV17,18 Horses: 0.5–2.0 mg/kg, IV19 |
1Martínez CS, Redondo JI, Rioja E. Comparison of two atracurium dosing regimens in dogs undergoing ophthalmic surgery. Vet Anaesth Analg. 2026;53(2):101188. doi:10.1016/j.vaa.2026.101188 2Macintire DK, Drobatz KJ, Haskins SC, Saxon WD. Drug formulary. In: Macintire DK, Drobatz KJ, Haskins SC, Saxon WD, eds. Manual of Small Animal Emergency and Critical Care Medicine. 2nd ed. John Wiley & Sons; 2012:524-651. doi:10.1002/9781119421870.app10 3Papastefanou A, Parsons E, Rioja, E. Reduction of train-of-four ratio following low dose neostigmine reversal of atracurium in a cat. Vet Anaesth Analg. 2022;49(2):222-224. doi:10.1016/j.vaa.2021.10.006 4Hildebrand SV, Bolich JA. Clinical use of atracurium in large animal species. Vet Anaesth Analg. 2002;29(2):108. doi:10.1046/j.1467-2995.2002.00078_27.x 5Ida KK, Van-Wijnsberghe AS, Tutunaru A, et al. Onset and duration of cis-atracurium neuromuscular block during fentanyl and lidocaine infusions in isoflurane-anaesthetised dogs. Vet Rec. 2020;187(5):e33. doi:10.1136/vr.105522 6Van Wijnsberghe AS, Ida KK, Dmitrovic P, Tutunaru A, Sandersen C. Neuromuscular blockade effects of cisatracurium in 11 cats undergoing ophthalmological surgery anaesthetised with isoflurane. J Feline Med Surg. 2022;24(4):402-406. doi:10.1177/1098612X211021829 7Tutunaru A, Dupont J, Gougnard A, Ida K, Serteyn D, Sandersen C. Retrospective evaluation of clinical use of cis-atracurium in horses. PLoS One. 2019;14(8):e0221196. doi:10.1371/journal.pone.0221196 8Dugdale AH, Adams WA, Jones RS. The clinical use of the neuromuscular blocking agent rocuronium in dogs. Vet Anaesth Analg. 2002;29(1):49-53. doi:10.1046/j.1467-2987.2001.00057.x 9Martin-Flores M, Hackman MC, Araos JD, Campoy L, Gleed RD. Duration of neuromuscular block is more variable and recovery time is shorter with rocuronium than cisatracurium in anesthetized dogs. Vet Ophthalmol. 2023;26(5):407-413. doi:10.1111/vop.13074 10Sakai DM, Zornow KA, Campoy L, et al. Intravenous rocuronium 0.3 mg/kg improves the conditions for tracheal intubation in cats: a randomized, placebo-controlled trial. J Feline Med Surg. 2018;20(12):1124-1129. doi:10.1177/1098612X18754425 11Martin-Flores M, Sakai DM, Portela DA, Borlle L, Campoy L, Gleed RD. Prevention of laryngospasm with rocuronium in cats: a dose-finding study. Vet Anaesth Analg. 2016;43(5):511-518. doi:10.1111/vaa.12342 12Kodaira K, Kakizaki M, Nagata SI, et al. Pharmacodynamics and pharmacokinetics of rocuronium in sevoflurane-anesthetized Thoroughbred horses. Vet Anaesth Analg. 2025;52(2):174-182. doi:10.1016/j.vaa.2024.12.006 13Martin-Flores M, Lorenzutti AM, Litterio NJ, et al. Speed of reversal of vecuronium neuromuscular block with different doses of neostigmine in anesthetized dogs. Vet Anaesth Analg. 2017;44(1):28-34. doi:10.1111/vaa.12395 14Martin-Flores M, Sakai DM. Neuromuscular blocking agents. In: Aarnes T, Lerche P, eds. Pharmacology in Veterinary Anesthesia and Analgesia. John Wiley & Sons; 2024:202-214. doi:10.1002/9781118975169.ch16 15Jones RS, Auer U, Mosing M. Reversal of neuromuscular block in companion animals. Vet Anaesth Analg. 2015;42(5),455-471. doi:10.1111/vaa.12272 16Lorenzutti AM, Martin-Flores M, Baldivieso JM, Himelfarb MA, Litterio NJ. Evaluation of neostigmine antagonism at different levels of vecuronium-induced neuromuscular blockade in isoflurane anesthetized dogs. Can Vet J. 2014;55(2):156-160. https://pmc.ncbi.nlm.nih.gov/articles/PMC3894876 17Martin-Flores M, Lorenzutti AM, Markmann AD, Araos J, Campoy L. Speed of reversal by sugammadex or neostigmine after vecuronium-induced neuromuscular block in dogs: randomized clinical trial and pharmacological modeling. Vet Anaesth Analg. 2025;52(3):328-337. doi:10.1016/j.vaa.2025.03.004 18Cesnik NM, D'Angelo Campos K, Cavaco JS, et al. Dose–response evaluation of sugammadex for reversal of deep rocuronium-induced neuromuscular block in cats. Vet Sci. 2025;12(12):1135. doi:10.3390/vetsci12121135 19Martin-Flores M, Sakai DM, Araos J, Campoy L. Low-dose sugammadex reverses moderate rocuronium-induced neuromuscular block in horses. Equine Vet J. 2025;57(1):265-270. doi:10.1111/evj.14066 | |
Reversal of Neuromuscular Blockade
Neostigmine is the most commonly used reversal agent. It inhibits the activity of acetylcholinesterase, which is responsible for the breakdown of ACh in the neuromuscular junction. As ACh accumulates within the junction, it competes with NMBAs for nicotinic receptors. If sufficient ACh accumulates, the neuromuscular block is reversed and function is restored.
Because ACh, and not neostigmine directly, is what competes with NMBAs, reversal by this mechanism is slow because sufficient time (typically 5–10 minutes) for ACh accumulation must elapse. Moreover, a ceiling of ACh concentration is reached when complete enzyme inhibition occurs. As a consequence, profound (complete) neuromuscular block cannot be effectively reversed, because the necessary concentrations of ACh simply cannot be reached.
The increase in ACh concentration can cause severe decreases in heart rate, among other muscarinic effects; therefore, neostigmine is almost always accompanied or preceded by atropine or glycopyrrolate.
Sugammadex is a novel selective relaxant binding agent specifically designed to reverse neuromuscular block from steroidal agents. Sugammadex binds to rocuronium or vecuronium in a nonreversible way. The sugammadex-NMBA complex has no paralytic effects and is eliminated through urine. Binding of sugammadex to the steroidal NMBA results in a fast and drastic decline in the plasma concentration of free NMBA; this is the mechanism by which function is restored.
Reversal with sugammadex is fast and has no muscarinic adverse effects. If sufficient sugammadex is administered, even profound neuromuscular block can be quickly reversed—something not possible with neostigmine.
Regardless of the strategy for reversing neuromuscular block, patients must be closely monitored for neuromuscular function, and ventilation support must be continued until neuromuscular function is restored. Thus it is often necessary to monitor neuromuscular transmission with a peripheral nerve stimulator.
Depolarizing Neuromuscular Blocking Agents
Succinylcholine (suxamethonium) is the only depolarizing NMBA available.
Depolarizing NMBAs occupy postjunctional cholinergic receptors and produce brief uncoordinated muscle contractions (fasciculations), followed by a period of flaccid relaxation—hence the depolarizing classification. Details of the mechanism are poorly understood; however, depolarization by ACh and muscle contraction are prevented by the presence of succinylcholine at nicotinic receptors.
Succinylcholine acts rapidly (within 20–50 seconds) after IV injection, and in most species its effect lasts 5–10 minutes (in dogs, typically longer). Succinylcholine is rapidly hydrolyzed by pseudocholinesterases in the plasma and liver in most species; however, substantial genetic differences exist in processing speed between individuals.
Succinylcholine is used in human emergency rooms to facilitate the rapid intubation of patients; however, it is rarely used in veterinary medicine today. In the past, it was used to induce paralysis in large animals or wildlife as a lone agent, so that various procedures or transport could be performed with absolute chemical restraint. This practice was ultimately deemed inhumane because the patients remained fully conscious and would experience all the pain and stress associated with the event.
Succinylcholine is associated with several adverse effects. Cardiac dysrhythmias and changes in blood pressure can occur. Hyperkalemia is typical after succinylcholine administration, and it can be fatal in susceptible animals, such as those with existing muscular diseases, including trauma, burns, and atrophy.
After recovery from succinylcholine-induced muscle paralysis, muscle damage and even myoglobinuria can develop. Malignant hyperthermia or clinical signs related to this syndrome might also result from the administration of succinylcholine in susceptible animals.
Because of the frequency and potential consequences of succinylcholine's adverse effects, as well as its duration of action, which is typically too short for most procedures, succinylcholine is not used in clinical veterinary practice. The agent is reserved primarily for emergency tracheal intubation in humans, where its rapid onset and short duration are particularly important.
No antagonists are available to reverse the action of succinylcholine.
The IV dosages of succinylcholine by species are as follows (1):
horses: 0.125–0.20 mg/kg (approximately 8 minutes duration)
cattle: 0.012–0.02 mg/kg (approximately 15 minutes duration)
dogs: 0.2–1.0 mg/kg (approximately 15–20 minutes duration)
cats: 0.2–1.0 mg/kg (approximately 3–5 minutes duration)
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Also see pet owner content regarding drugs used to treat bone and muscle disorders.
References
Keegan RD. Muscle relaxants and neuromuscular blockade. In: Grimm KA, Lamont LA, Tranquilli WJ, Greene SA, Robertson SA, eds. Veterinary Anesthesia and Analgesia. 5th ed. John Wiley & Sons; 2015:260-276. doi:10.1002/9781119421375.ch14
