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Response Letter to Editor
- Tae-Hyung Han (17 January 2009)
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The onset of rocuronium in patients with major burn
- MOHAMMAD EL-ORBANY, Medical College of Wisconsin (10 January 2009)
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Tae-Hyung Han
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We thank Dr. El-Orbany for his comments regarding our paper.1 His letter, citing the study of Badetti and colleagues,2 reiterates the point on the importance of time and magnitude of the burn in regard to the resistance to the neuromuscular effects of non-depolarizing neuromuscular relaxants in burned patients. Several of our previous studies, well referenced in the Badetti paper (13 of 31 references), indeed document this quite well. It is notable and comforting that the study of Badetti et al. with vecuronium confirms exactly what was reported by us for the same drug seventeen years earlier.3 Dr. El-Orbany referring to the Badetti study suggests that the ED95 for 20%, 20-40%, 40- 60% and ≥ 60% body surface area burn be increased by a factor of 1.3, 1.9, 2.5, and 2.9, respectively, compared to controls. However, non- depolarizing relaxant clinically tested do not all have the same magnitude of shift in ED95 following burns. Quite in contrast, burned patients sometimes do not demonstrate resistance to mivacurium.4 Therefore, findings from the study of one drug (e.g. vecuronium) cannot be easily applied to another drug (rocuronium). Dr. El-Orbany fails to mention that this shift (increase) in dosing is for ED95. In order to have a rapid onset of effect, one has to use a higher dose of the relaxant. For example, in normal patients the ED95 for rocuronium is 0.3 mg kg-1 and the intubating dose is 0.9-1.0 mg kg-1. In a previous study consisting of patients with a mean of 35% body surface area burn, a 4 × ED95 (1.2 mg kg-1) of rocuronium had an onset time of ≥ 86 seconds for ≥ 90% paralysis.5 Based on the recommendation of Dr. El-Orbany for patients with mean body surface area burn of 40%, a dose escalation by 2.5–2.9 fold would have been sufficient. In the study reported by us,1 had we used the suggested 2.5-2.9 fold higher dose (0.9 mg kg-1), the onset time for ≥ 90% paralysis would have exceeded 2 minutes, as reported previously.5 It is for this reason that we used 5 fold or 5 × ED95 (1.5 mg kg-1) in the recent study. Despite this very high dose, the onset time for ≥ 90% paralysis was ~70 seconds. The aim of our study was not to achieve effective paralysis but rapid onset of effective paralysis. As documented by us previously and recently reviewed,6,7 the sensitivity to neuromuscular relaxants can vary not only with time and magnitude of burn, but also by presence or absence of edema, concomitant prolonged use of muscle relaxants in the intensive care unit, immobilization, and/or severity of inflammation/infection, to name some other variables.5-7 These variables can affect acetylcholine receptor number (postjunctionally), acetylcholine release (prejunctionally) and drug binding plasma protein components and all of these variables can effect response to relaxants.6-8 Thus, it is too simplistic to assume that every burned patient, based on burn size, will have graded increments in doses. In order to achieve rapid onset of paralysis, it, therefore, seems prudent to favor an overdose rather than under-dose. Under-dosing would result in a very prolonged onset resulting in delay of intubation time with risk for desaturation and/or aspiration. It is notable that even with 1.5 mg kg-1 the onset time was yet longer than 60 seconds. It is possible that higher doses may be required or a ceiling effect may be seen with higher doses. Recovery from neuromuscular paralysis is more rapid following burns. Alternatively the recovery could be enhanced by anticholinesterases or by the new cyclodextrin reversal drug (Sugammadex®), which has not been tested in burns. References: 1. Han TH, Martyn JAJ. Onset and effectiveness of rocuronium for rapid onset of paralysis in patients with major burns: priming or large bolus. Br J Anaesth 2009; 102: 55-56. 2. Badetti C, Pascal L, Bernini V, Manelli JC. Résistance au vecuronium chez le brûlé. Influence de la surface brûlée sur la dose efficace 95. Ann Fr Anesth Réanim 1996; 15: 135-41. 3. Mills AK, Martyn JAJ. Neuromusular blockade with vecuronium in paediatric patients with burn injury. Br J Clin Pharmacol 1989; 28: 155-9. 4. Martyn JAJ, Chang Y, Goudsouzian NG, Patel SS. Pharmacodynamics of mivacurium chloride in 13- to 18-yr-old adolescents with thermal injury. Br J Anaesth 2002; 89: 580-5. 5. Han T, Kim H, Bae J, Kim K, Martyn JAJ. Neuromuscular pharmacodynamics of rocuronium in patients with major burns. Anesth Analg 2004; 99: 386-92. 6. Martyn JAJ, Richtsfeld M. Succinylcholine-induced hyperkalemia in acquired pathologic states: etiologic factors and molecular mechanisms. Anesthesiology 2006; 104: 158-69. 7. Martyn JAJ, Fukushima Y, Chon JY, Yang HS. Muscle relaants in burns, trauma, and critical illness. Int Anesthesiol Clin 2006; 44: 123-43. 8. Fink H, Helming M, Unterbuchner C, Lenz A, Neff F, Martyn JAJ, Blobner M. Systemic inflammatory response syndrome increases immobility-induced neuromuscular weakness. Crit Care Med 2008; 36: 910-6. Conflict of Interest:None declared |
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MOHAMMAD EL-ORBANY, Associate Professor Department of Anesthesiology, Medical College of Wisconsin
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Editor, Han and Martyn studied the onset of rocuronium block in major burn patients using 1.5 mg kg-1 to have a rapid onset of paralysis (1). It is to be noted that the study population had 40 (2) % burnt surface area (BSA). Patients with higher or lower BSA may need a higher or lower dose than the recommended one. More proliferation of immature fetal-type acetylcholine receptors and more increase in the volume of distribution are expected with the increase in BSA (2). The magnitude of burn injury and the magnitude of resistance to nondepolarizing neuromuscular blockers are thus directly related as concluded by Badetti and colleagues (3). To calculate the dose that achieves the same response they suggested the use of the following correction factors: 1.3 for BSA under 20%, 1.9 for BSA between 20 and 40%, 2.5 for BSA between 40 and 60% and 2.9 for a BSA above 60%. References: 1- Han TH, Martyn JAJ. Onset and effectiveness of rocuronium for rapid onset of paralysis in patients with major burns: priming or large bolus. Br J Anaesth 2009; 102:55-60. 2- Han T, Kim H, Bae J, Kim K, Martyn JA. Neuromuscular pharmacodynamics of rocuronium in patients with major burns. Anesth Analg 2004; 99: 386-92. 3- Badetti C, Pascal L, Bernini V, Manelli JC. Resistance to vecuronium in burnt patients. Influence of the burnt surface on the effectiveness of the dose 95. Ann Fr Anesth Reanim 1996; 15: 135-41. Conflict of Interest:None declared |
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