Elevated Plasma Binding Cannot Account for the Burnrelated d-Tubocurarine Hyposensitivity

Leibel, Wayne S.; Martyn, J. A. Jeevendra; Szyfelbein, S.K.; Miller, Keith W.

doi:10.1097/00000542-198105000-00006

Cited by 34 publications

(10 citation statements)

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“…The aetiology of the resistance to nondepolarizing relaxants in burned patients is multifactorial and includes .altered protein binding (Leibel et al, 1981), altered pharmacokinetics (Martyn et al, 1982) and circulating mediators (Storella et al, 1988). In addition, Kim et al (1988a) have shown that the numbers of nicotinic acetylcholine receptors in the diaphragm increase following thermal injury to the trunk of the rat.…”

Section: Discussionmentioning

confidence: 99%

Neuromuscular Blockade with Vecuronium in Paediatric Patients with Burn Injury

Mills

Martyn

1990

Survey of Anesthesiology

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1 The effect of body surface area (BSA) burn injury on neuromuscular pharmacodynamics of vecuronium was evaluated. 2 The neuromuscular responses of 15 burned children were compared with those in five controls. 3 The effective dose for 50% suppression of twitch tension (ED50) was 34 ,ug kg-' for patients with < 40% BSA burn, 55 ,ug kg-1 for 40-60% BSA burn, and 65 ,ug kg-1 for patients with > 60% BSA burn. These values were significantly higher than the value for control patients, which was 18 pug kg-'.4 Burn injury induces a resistance to the neuromuscular effects of vecuronium, the magnitude of which is related to burn size.

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Section: Discussionmentioning

confidence: 99%

Neuromuscular Blockade with Vecuronium in Paediatric Patients with Burn Injury

Mills

Martyn

1990

Survey of Anesthesiology

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“…However, binding of D-tubocurarine by a plasma protein has been shown to be responsible for only a small part of the observed hyposensitivity, minimally explaining resistance to the neuromuscular blocking agent seen in burns. 23 Similarly, despite the clinically significant relaxant resistance after chronic phenytoin therapy, changes in free fraction between phenytoin and the control group due to changes in AAG was only 67% vs 75%, not pharmacologically significant enough to explain the role of plasma protein binding. 24 Regardless, no reports have indicated that the increased protein binding of drug results in the slower offset of neuromuscular blocking agent-induced paralysis.…”

Section: Discussionmentioning

confidence: 96%

Neuromuscular Pharmacodynamics of Mivacurium in Adults With Major Burns

Han¹,

Martyn²

2012

Survey of Anesthesiology

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Editor's key points † Patients with burns can be resistant non-depolarizers and have low pseudocholinesterase. † These conditions could have an advantageous effect on mivacurium dynamics in burns. † In burns patients, mivacurium onset was slower and action more prolonged than in controls. † Mivacurium does not offer any clinical advantage in this setting.Background. Mivacurium is metabolized by plasma pseudocholinesterase (PChE) enzyme, which is decreased in burns. We tested whether the decreased metabolism of mivacurium due to decreased PChE activity can overcome the pharmacodynamic resistance to non-depolarizing relaxants previously seen in major burns.

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“…For both doses the recovery time in burned children was significantly prolonged compared with reconstructive children when equipotent doses were compared. That 5-25% recovery was prolonged in burned patients after such a large dose can be ascribed to any of the following causes: a) Increased binding of muscle relaxants occurs after burn injury (13). Because only the free fraction of drug is filtered across the glomerulus of the kidney, the increased binding (decreased free fraction) of muscle relaxants results in decreased renal elimination of drug, which, in turn, can result in a prolonged twitch recovery time; b) the higher dose itself may contribute to the prolonged recovery time; and c) depressed liver function and drug metabolism seen after burn injury (14) may also play a role in prolonging recovery of normal twitch response.…”

Section: Discussionmentioning

confidence: 99%

Cardiovascular and Neuromuscular Responses to High-dose Pancuronium-Metocurine in Pediatric Burned and Reconstructive Patients

Hagen

Martyn

Szyfelbein

et al. 1986

Anesthesia & Analgesia

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responses to high-dose pancuronium-metocurine in pediatric burned and reconstructive patients. Anesth Analg 1986;65:1340-4.The efficacy of the combined use of pancuronium and metocurine (Pm-MTC) in high doses to produce rapid-onset niuscle paralysis was evaluated in 15 patients with acute burns and 18 recovered burned patients scheduled for reconstructive surgery. Two and three times the previously determined ED,, of the cornbination for each group was used. (ED,, for Pm-MTC conibination is 0.03210.129 tnglkg for acute burns and 0.013l0.051 mglkg for reconstructive patients.) DoublinX ED,, produced 95% paralysis in 3.1 i 0.9 min in acutely burned children and in 4.3 2 0.7 min in reconstructive children (mean i SEMI. These onset times were not significantly different from tach other. Tripling the ED, of the combination in burned children reduced the onset tirne to 1.3 i 0.14 min, but this was not significantly different from 2 x EDs, onset time in burned patients. The admitiisfrafion o f 3 x €Dg5 to the reconstructive group, however, resulted in a significantly more rapid onset time of 1.8 +-0.4 niin compared with 2 x EDs, in the same population. With 3 x ED,, the onset times between burii and reconstructive patients were not significantly different. Time for recovery of twitch to 25% of control twitch heixht (75% twitch depression) u7as significantly prolonged in burned patients compared with reconstructive patients for equipotent doses administered. Although the occasional patient showed proniinent changes in heart rate and blood pressure, overall cardiovascular stability was impressive. Therefore, high doses of Pm-MTC combination can be used in combination to produce more rapid onset of paralysis in burned patients and may also represent an alternative to succinylcholine in other situations wherein there is risk of succinylcholine-induced hyperkalemia. This technique does not provide as rapid onset of paralysis as succinylcholine.Succinylcholine continues to be the drug of choice for rapid-onset neuromuscular (NM) paralysis in clinical emergencies, such as laryngospasm and the full stomach. In certain pathologic states, such as burns and denervation syndromes, however, the depolarizing NM relaxant succinylcholine is contraindicated because of the potential for lethal hyperkalemia (1).Increasing the dose of nondepolarizing NM relax-

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Elevated Plasma Binding Cannot Account for the Burnrelated d-Tubocurarine Hyposensitivity

Cited by 34 publications

References 0 publications

Neuromuscular Blockade with Vecuronium in Paediatric Patients with Burn Injury

Neuromuscular Blockade with Vecuronium in Paediatric Patients with Burn Injury

Neuromuscular Pharmacodynamics of Mivacurium in Adults With Major Burns

Cardiovascular and Neuromuscular Responses to High-dose Pancuronium-Metocurine in Pediatric Burned and Reconstructive Patients

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