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Advantages of and Guidelines for Using Neuromuscular Blocking Agents
NEUROMUSCULAR BLOCKING AGENTS
347
16. Savarese JJ, Ali HH, Basta SJ, et a!: The clinical neuromuscular pharmacology of mivacurium chloride (BW B1090U). Anesthesiology 68:723-732, 1988 17. Savarese JJ, Basta SJ, Ali HH, et a!: Cardiovascular effects of BW B1090U under nitrous oxide-oxygen-thiopental-fentanyl anesthesia. Anesthesiology 63:A319, 1985 18. Savarese JJ, Ginsburg S, Braswell L, et a!: Actions at neuromuscular and esteratic cholinoceptive sites of some phenylene diacryloyl bis-cholinium esters. J Pharm Exp Ther 208:436-445, 1979 19. Scott RPF, Savarese JJ: The cardiovascular and autonomic effects of neuromuscular blocking agents. In Katz RL, ed: Muscle Relaxants: Basic and Clinical Aspects. New York, Gtune & Stratton, 1985, pp 117-141 20. Scott RPF, Savarese JJ, Basta SJ, et a!: Atracurium: Clinical strategies for preventing histamine release and attenuating the hemodynamic response. Br J Anaesth 57:550553, 1985 21. Standaert FG: Donuts and holes: Molecules and muscle relaxants. In Katz RL, ed: Muscle Relaxants: Basic and Clinical Aspects. New York, Grune & Stratton, 1985, pp 1-18 22. Viby-Mogensen J: Interaction of other drugs with muscle relaxants. In Katz RL, ed: Muscle Relaxants: Basic and Clinical Aspects. New York, Grune & Stratton, 1985, pp 233-256 23. Weber S, Brandom BW, Powers OM, eta!: Mivacurium chloride (BW B1090U) induced neuromuscular blockade during nitrous oxide-isoflurane and nitrous oxide-narcotic anesthesia in adult surgical patients. Anesth Analg 67:495-499, 1988
Advantages of and Guidelines for Using Neuromuscular Blocking Agents Jan E. Ilkiw, BVSc, PhD From the Department of Surgery, University of California, Davis, School of Veterinary Medicine, Davis, California
The use of neuromuscular blocking agents should be considered in the anesthetic management of certain small animal patients. The neuromuscular blocking agent that we use most frequently is atracurium besylate. This drug is reported to have minimal cardiovascular effects at clinical doses/ to be eliminated independent of liver or kidney function/ and to have a short duration of action with no apparent cumulative effect. 1 Atracurium can be administered by either repeated bolus or combined bolus and infusion techniques. If a bolus technique is used, a calculated dose of 0.25 mg/kg is administered IV over about 1 minute. Neuromuscular paralysis, monitored with a peripheral nerve stimulator, ensues for about 30 minutes. If further paralysis is required, another dose (0.15 mg/kg) may be administered. If a bolus and infusion technique is used, atracurium is administered IV at calculated doses of 0.1 mg/kg every 3 minutes until the 1st twitch of the train-of-four only is evident. At the same time, an IV infusion of atracurium is started
348
NEUROMUSCULAR BLOCKING AGENTS
and the infusion adjusted to maintain the 1st twitch. As a guideline, an infusion of 3 to 4 f.Lg/kg/min is usually needed with inhalant techniques, such as isoflurane, whereas an infusion of 7 to 8 f.Lg/kg/min is required when balanced techniques using opioids and low dose inhalants are administered. In most cases when the surgery is completed, we antagonize the effects of atracurium by IV administration of edrophonium at a calculated dose of 0.5 mg/kg. Bradycardia may be associated with edrophonium administration. Thus either atropine administration should precede edrophonium administration, or edrophonium should be administered slowly and the heart rate closely monitored. When muscle relaxants are used as part of a balanced anesthetic technique, the anesthesiologist must be familiar with their use, the patient's respiration must be controlled, neuromuscular and cardiovascular function must be adequately monitored, and anesthetic agents must be administered in doses sufficient to induce unconsciousness and analgesia. Neuromuscular blocking agents should always be considered adjuncts and should never replace anesthetic agents. At the completion of surgery, if there is any doubt that residual blockade could be present, the effects of the neuromuscular blocking drug must be reversed. If these guidelines are adhered to, the advantages of neuromuscular blocking agents far outweigh their risks and disadvantages, and they can safely be used. The main advantage of neuromuscular blocking agents is that they facilitate surgical exposure and minimize tissue trauma by inducing muscle relaxation. Anesthetic techniques that depend primarily on opioids, nitrous oxide, and low dose inhalant agents produce little muscle relaxation. 12 Inhalant agents, such as isoflurane, enflurane, and diethyl ether, induce measurable neuromuscular blockade only at deep anesthetic levels. 6 This level of anesthesia is associated with profound cardiovascular and respiratory depression. 4 •11 In humans, at least 75% reduction of the evoked muscle response following a single twitch stimulation is needed to induce adequate abdominal muscle relaxation. 2 Thus neuromuscular blocking agents greatly facilitate exposure to organs situated deep in thoracic or abdominal cavities, such as adrenal glands, kidney and liver, and vascular structures such as aorta and vena cava. They also expedite the removal of any large abdominal or thoracic tumor by allowing better surgical exposure. Neuromuscular blocking agents facilitate orthopedic manipulations such as dislocation and fracture reduction by abolishing skeletal muscle tone. 5 Our orthopedic surgeons report that dislocations and fractures that are difficult to reduce under standard inhalant anesthetic techniques are more easily reduced following administration of a neuromuscular blocking drug, even though neuromuscular drugs do not overcome the muscle contracture that occurs following a fracture. We commonly include a neuromuscular blocking agent in our anesthetic technique for shoulder joint exploration in large, heavily muscled breeds, such as Rottweilers, to facilitate visualization of the humoral head and to expedite surgical manipulations. The use of neuromuscular
NEUROMUSCULAR BLOCKING AGENTS
349
blocking drugs for certain orthopedic procedures facilitates the operation and decreases surgical and anesthetic time. We currently administer neuromuscular blocking drugs as part of our anesthetic technique for some ocular (penetrating wounds) and all intraocular (cataract extraction or lens luxation, corneal repair or transplant, repair of detached retina, open or closed vitrectomy, and glaucoma filtering) operations. The anesthetic management of patients with penetrating ocular wounds is difficult because of the danger of blindness from vitreous extrusion if intraocular pressure is increased. Coughing and vomiting greatly increase intraocular pressure and should be avoided during the induction. 3 Nondepolarizing neuromuscular blocking agents do not affect intraocular pressure 3 and can be used as part of the induction technique to prevent coughing associated with intubation. The disadvantage of these agents is the long onset of action, with atracurium (0.5 mg/kg IV) taking 2 minutes to block responses so that intubation is smooth and atraumatic. 8 To prevent coughing associated with intubation, we have preoxygenated the patient using a face mask and then administered atracurium 0.25 mg/kg IV followed by 2.5 to 5.0 mg/kg of thiamylal sodium. Respiration is controlled via face mask, and the patient is intubated 2 minutes after administration of the atracurium. An alternative technique reported in humans 8 is the use of a small, priming dose (atracurium, 0.1 mg/kg) followed in 2 to 3 minutes by a larger, paralyzing dose (0.4 mg/kg), which permits intubation within 1 minute after the 2nd dose. The advantages of using neuromuscular blocking drugs for intraocular surgery are no intraoperative increases in intraocular pressure and therefore no chance of vitreous extrusion and a still eye with a central pupil and a soft globe, which facilitates delicate microscopic techniques. For intraocular surgery, the twitch response following nerve stimulation should be reduced to 5% to 10% of baseline. 3 We have also found this technique to be beneficial for organ transplantation because it provides excellent surgical conditions for the microscopic techniques that are used for vascular anastomosis. Neuromuscular blocking drugs are often used as part of a balanced anesthetic technique for cesarean section. These drugs have low lipid solubility and are highly ionized at physiologic pH, resulting in insignificant placental transfer, as long as conventional doses are administered.10 They thus provide optimum operating conditions without the need for deepening anesthesia. Provided that the patient is unconscious and autonomic responses to noxious stimuli are blocked, neuromuscular agents may be used to decrease the level of anesthesia obtained from potent inhalant agents. This is especially beneficial in the management of critically ill patients with cardiovascular instability. In these dogs, we currently use a balanced anesthetic technique consisting of atracurium administration to induce neuromuscular blockade, low dose isoflurane administration to induce unconsciousness, and fentanyl infusion to decrease the need for inhalant anesthesia and to blunt autonomic response to noxious stimuli. We find that the anesthetic depth and the cardiovascular system
350
NEUROMUSCULAR BLOCKING AGENTS
remain stable with this technique and the surgeons enjoy good operating conditions. SUMMARY
Neuromuscular blocking agents, although not commonly used in veterinary practice, should be considered when muscle relaxation is needed to facilitate surgical exposure and minimize tissue trauma. These drugs should be administered only once respiration has been controlled and anesthetic agents have been administered to induce unconsciousness and analgesia. Following administration of neuromuscular blocking drugs, neuromuscular and cardiovascular function must be monitored.
References 1. Ali HH, Savarese JJ, Basta SJ, et al: Evaluation of cumulative properties of the three new nondepolarizing neuromuscular blocking drugs BW A444U, atracurium and vecuronium. Br J Anaesth 55:107s, 1983 2. de Jong RH: Controlled relaxation. I. Quantitation of electromyogram with abdominal relaxation. JAMA 197:113, 1966 3. Donlon JV: Anesthesia for eye, ear, nose, and throat. In Miller RD, ed: Anesthesia, ed 2. New York, Churchill Livingstone, 1986, p 1837 4. Grandy JL, Hodgson DS, Dunlop Cl, et al: Cardiopulmonary effects of halothane anesthesia in cats. Am J Vet Res 50:1729, 1989 5. Hall LW, Clarke KW: Relaxation of the skeletal muscles during anaesthesia. In Veterinary Anaesthesia, ed 8. London, Bailliere Tindall, 1983, p 114 6. Miller RD, Savarese JJ: Pharmacology of muscle relaxants and their antagonists. In Miller RD, ed: Anesthesia, ed 2. New York, Churchill Livingstone, 1986, p 889 7. Neill EAM, Chapple DJ: Metabolic studies in the cat with atracurium: A neuromuscular blocking agent designed for nonenzymatic inactivation at physiological pH. Xenobiotica 12:203, 1982 8. Payne JP: Atracurium. In Katz RL, ed: Muscle Relaxants: Basic and Clinical Aspects. New York, Grune & Stratton 1985, p 100 9. Scott RPF, Savarese JJ: The cardiovascular and autonomic effects of neuromuscular blocking agents. In RL Katz, ed: Muscle Relaxants: Basic and Clinical Aspects. New York, Grune & Stratton, 1985, p 117 10. Shnider SM, Levinson G: Anesthesia for cesarean section. In Shnider SM, Levinson G, eds: Anesthesia for Obstetrics, ed 2. Baltimore, Williams & Wilkins, 1987, p 159 11. Steffey EP, Gillespie JR, Berry ]D, et al: Circulatory effects of halothane and halothane-nitrous oxide anesthesia in the dog: Spontaneous ventilation. Am J Vet Res 36:197, 1975 12. Stoelting RK: Inhaled anesthetics. In Pharmacology and Physiology in Anesthetic Practice. Philadelphia, JB Lippincott Company, 1987, p 35
347
16. Savarese JJ, Ali HH, Basta SJ, et a!: The clinical neuromuscular pharmacology of mivacurium chloride (BW B1090U). Anesthesiology 68:723-732, 1988 17. Savarese JJ, Basta SJ, Ali HH, et a!: Cardiovascular effects of BW B1090U under nitrous oxide-oxygen-thiopental-fentanyl anesthesia. Anesthesiology 63:A319, 1985 18. Savarese JJ, Ginsburg S, Braswell L, et a!: Actions at neuromuscular and esteratic cholinoceptive sites of some phenylene diacryloyl bis-cholinium esters. J Pharm Exp Ther 208:436-445, 1979 19. Scott RPF, Savarese JJ: The cardiovascular and autonomic effects of neuromuscular blocking agents. In Katz RL, ed: Muscle Relaxants: Basic and Clinical Aspects. New York, Gtune & Stratton, 1985, pp 117-141 20. Scott RPF, Savarese JJ, Basta SJ, et a!: Atracurium: Clinical strategies for preventing histamine release and attenuating the hemodynamic response. Br J Anaesth 57:550553, 1985 21. Standaert FG: Donuts and holes: Molecules and muscle relaxants. In Katz RL, ed: Muscle Relaxants: Basic and Clinical Aspects. New York, Grune & Stratton, 1985, pp 1-18 22. Viby-Mogensen J: Interaction of other drugs with muscle relaxants. In Katz RL, ed: Muscle Relaxants: Basic and Clinical Aspects. New York, Grune & Stratton, 1985, pp 233-256 23. Weber S, Brandom BW, Powers OM, eta!: Mivacurium chloride (BW B1090U) induced neuromuscular blockade during nitrous oxide-isoflurane and nitrous oxide-narcotic anesthesia in adult surgical patients. Anesth Analg 67:495-499, 1988
Advantages of and Guidelines for Using Neuromuscular Blocking Agents Jan E. Ilkiw, BVSc, PhD From the Department of Surgery, University of California, Davis, School of Veterinary Medicine, Davis, California
The use of neuromuscular blocking agents should be considered in the anesthetic management of certain small animal patients. The neuromuscular blocking agent that we use most frequently is atracurium besylate. This drug is reported to have minimal cardiovascular effects at clinical doses/ to be eliminated independent of liver or kidney function/ and to have a short duration of action with no apparent cumulative effect. 1 Atracurium can be administered by either repeated bolus or combined bolus and infusion techniques. If a bolus technique is used, a calculated dose of 0.25 mg/kg is administered IV over about 1 minute. Neuromuscular paralysis, monitored with a peripheral nerve stimulator, ensues for about 30 minutes. If further paralysis is required, another dose (0.15 mg/kg) may be administered. If a bolus and infusion technique is used, atracurium is administered IV at calculated doses of 0.1 mg/kg every 3 minutes until the 1st twitch of the train-of-four only is evident. At the same time, an IV infusion of atracurium is started
348
NEUROMUSCULAR BLOCKING AGENTS
and the infusion adjusted to maintain the 1st twitch. As a guideline, an infusion of 3 to 4 f.Lg/kg/min is usually needed with inhalant techniques, such as isoflurane, whereas an infusion of 7 to 8 f.Lg/kg/min is required when balanced techniques using opioids and low dose inhalants are administered. In most cases when the surgery is completed, we antagonize the effects of atracurium by IV administration of edrophonium at a calculated dose of 0.5 mg/kg. Bradycardia may be associated with edrophonium administration. Thus either atropine administration should precede edrophonium administration, or edrophonium should be administered slowly and the heart rate closely monitored. When muscle relaxants are used as part of a balanced anesthetic technique, the anesthesiologist must be familiar with their use, the patient's respiration must be controlled, neuromuscular and cardiovascular function must be adequately monitored, and anesthetic agents must be administered in doses sufficient to induce unconsciousness and analgesia. Neuromuscular blocking agents should always be considered adjuncts and should never replace anesthetic agents. At the completion of surgery, if there is any doubt that residual blockade could be present, the effects of the neuromuscular blocking drug must be reversed. If these guidelines are adhered to, the advantages of neuromuscular blocking agents far outweigh their risks and disadvantages, and they can safely be used. The main advantage of neuromuscular blocking agents is that they facilitate surgical exposure and minimize tissue trauma by inducing muscle relaxation. Anesthetic techniques that depend primarily on opioids, nitrous oxide, and low dose inhalant agents produce little muscle relaxation. 12 Inhalant agents, such as isoflurane, enflurane, and diethyl ether, induce measurable neuromuscular blockade only at deep anesthetic levels. 6 This level of anesthesia is associated with profound cardiovascular and respiratory depression. 4 •11 In humans, at least 75% reduction of the evoked muscle response following a single twitch stimulation is needed to induce adequate abdominal muscle relaxation. 2 Thus neuromuscular blocking agents greatly facilitate exposure to organs situated deep in thoracic or abdominal cavities, such as adrenal glands, kidney and liver, and vascular structures such as aorta and vena cava. They also expedite the removal of any large abdominal or thoracic tumor by allowing better surgical exposure. Neuromuscular blocking agents facilitate orthopedic manipulations such as dislocation and fracture reduction by abolishing skeletal muscle tone. 5 Our orthopedic surgeons report that dislocations and fractures that are difficult to reduce under standard inhalant anesthetic techniques are more easily reduced following administration of a neuromuscular blocking drug, even though neuromuscular drugs do not overcome the muscle contracture that occurs following a fracture. We commonly include a neuromuscular blocking agent in our anesthetic technique for shoulder joint exploration in large, heavily muscled breeds, such as Rottweilers, to facilitate visualization of the humoral head and to expedite surgical manipulations. The use of neuromuscular
NEUROMUSCULAR BLOCKING AGENTS
349
blocking drugs for certain orthopedic procedures facilitates the operation and decreases surgical and anesthetic time. We currently administer neuromuscular blocking drugs as part of our anesthetic technique for some ocular (penetrating wounds) and all intraocular (cataract extraction or lens luxation, corneal repair or transplant, repair of detached retina, open or closed vitrectomy, and glaucoma filtering) operations. The anesthetic management of patients with penetrating ocular wounds is difficult because of the danger of blindness from vitreous extrusion if intraocular pressure is increased. Coughing and vomiting greatly increase intraocular pressure and should be avoided during the induction. 3 Nondepolarizing neuromuscular blocking agents do not affect intraocular pressure 3 and can be used as part of the induction technique to prevent coughing associated with intubation. The disadvantage of these agents is the long onset of action, with atracurium (0.5 mg/kg IV) taking 2 minutes to block responses so that intubation is smooth and atraumatic. 8 To prevent coughing associated with intubation, we have preoxygenated the patient using a face mask and then administered atracurium 0.25 mg/kg IV followed by 2.5 to 5.0 mg/kg of thiamylal sodium. Respiration is controlled via face mask, and the patient is intubated 2 minutes after administration of the atracurium. An alternative technique reported in humans 8 is the use of a small, priming dose (atracurium, 0.1 mg/kg) followed in 2 to 3 minutes by a larger, paralyzing dose (0.4 mg/kg), which permits intubation within 1 minute after the 2nd dose. The advantages of using neuromuscular blocking drugs for intraocular surgery are no intraoperative increases in intraocular pressure and therefore no chance of vitreous extrusion and a still eye with a central pupil and a soft globe, which facilitates delicate microscopic techniques. For intraocular surgery, the twitch response following nerve stimulation should be reduced to 5% to 10% of baseline. 3 We have also found this technique to be beneficial for organ transplantation because it provides excellent surgical conditions for the microscopic techniques that are used for vascular anastomosis. Neuromuscular blocking drugs are often used as part of a balanced anesthetic technique for cesarean section. These drugs have low lipid solubility and are highly ionized at physiologic pH, resulting in insignificant placental transfer, as long as conventional doses are administered.10 They thus provide optimum operating conditions without the need for deepening anesthesia. Provided that the patient is unconscious and autonomic responses to noxious stimuli are blocked, neuromuscular agents may be used to decrease the level of anesthesia obtained from potent inhalant agents. This is especially beneficial in the management of critically ill patients with cardiovascular instability. In these dogs, we currently use a balanced anesthetic technique consisting of atracurium administration to induce neuromuscular blockade, low dose isoflurane administration to induce unconsciousness, and fentanyl infusion to decrease the need for inhalant anesthesia and to blunt autonomic response to noxious stimuli. We find that the anesthetic depth and the cardiovascular system
350
NEUROMUSCULAR BLOCKING AGENTS
remain stable with this technique and the surgeons enjoy good operating conditions. SUMMARY
Neuromuscular blocking agents, although not commonly used in veterinary practice, should be considered when muscle relaxation is needed to facilitate surgical exposure and minimize tissue trauma. These drugs should be administered only once respiration has been controlled and anesthetic agents have been administered to induce unconsciousness and analgesia. Following administration of neuromuscular blocking drugs, neuromuscular and cardiovascular function must be monitored.
References 1. Ali HH, Savarese JJ, Basta SJ, et al: Evaluation of cumulative properties of the three new nondepolarizing neuromuscular blocking drugs BW A444U, atracurium and vecuronium. Br J Anaesth 55:107s, 1983 2. de Jong RH: Controlled relaxation. I. Quantitation of electromyogram with abdominal relaxation. JAMA 197:113, 1966 3. Donlon JV: Anesthesia for eye, ear, nose, and throat. In Miller RD, ed: Anesthesia, ed 2. New York, Churchill Livingstone, 1986, p 1837 4. Grandy JL, Hodgson DS, Dunlop Cl, et al: Cardiopulmonary effects of halothane anesthesia in cats. Am J Vet Res 50:1729, 1989 5. Hall LW, Clarke KW: Relaxation of the skeletal muscles during anaesthesia. In Veterinary Anaesthesia, ed 8. London, Bailliere Tindall, 1983, p 114 6. Miller RD, Savarese JJ: Pharmacology of muscle relaxants and their antagonists. In Miller RD, ed: Anesthesia, ed 2. New York, Churchill Livingstone, 1986, p 889 7. Neill EAM, Chapple DJ: Metabolic studies in the cat with atracurium: A neuromuscular blocking agent designed for nonenzymatic inactivation at physiological pH. Xenobiotica 12:203, 1982 8. Payne JP: Atracurium. In Katz RL, ed: Muscle Relaxants: Basic and Clinical Aspects. New York, Grune & Stratton 1985, p 100 9. Scott RPF, Savarese JJ: The cardiovascular and autonomic effects of neuromuscular blocking agents. In RL Katz, ed: Muscle Relaxants: Basic and Clinical Aspects. New York, Grune & Stratton, 1985, p 117 10. Shnider SM, Levinson G: Anesthesia for cesarean section. In Shnider SM, Levinson G, eds: Anesthesia for Obstetrics, ed 2. Baltimore, Williams & Wilkins, 1987, p 159 11. Steffey EP, Gillespie JR, Berry ]D, et al: Circulatory effects of halothane and halothane-nitrous oxide anesthesia in the dog: Spontaneous ventilation. Am J Vet Res 36:197, 1975 12. Stoelting RK: Inhaled anesthetics. In Pharmacology and Physiology in Anesthetic Practice. Philadelphia, JB Lippincott Company, 1987, p 35