mivacurium and Burns

Burned patients are usually resistant to the neuromuscular effects of nondepolarizing relaxants, mostly because of receptor changes. The magnitude of the resistance is related to burn size and time after burn. Mivacurium is a muscle relaxant, degraded by plasma cholinesterase, whose enzyme activity is decreased in burns. The present study tested the hypothesis that burn-induced depressed plasma cholinesterase activity counteracts the receptor-mediated resistance, resulting in a lack of resistance to mivacurium.. Burned patients (n = 23), aged 2-12 yr, subclassified into burns of 10-30% or > 30% of body surface, were studied at < or = 6 days and again at 1-12 weeks after burn if possible. Thirteen additional patients served as controls. Neuromuscular variables monitored included onset and recovery following bolus dose, continuous infusion rates required to maintain 95 +/- 4% paralysis, and recovery rates following infusion.. The onset times of maximal twitch suppression were not different between burns and controls, but recovery to 25% of baseline twitch height was prolonged in patients with > 30% burn irrespective of time after injury. The continuous infusion rates to maintain twitch suppression at 95 +/- 4% were not different between groups. The recovery indices, including train-of-four to > 75%, 25-75%, or 5-95% in burned patients, were similar or prolonged compared with controls. The prolonged recovery in burned patients was inversely related to plasma cholinesterase activity (R2 = 0.86, r = -0.93, P < 0.001), and the decreased plasma cholinesterase activity was related to burn size and time after burn.. A normal mivacurium dosage (0.2 mg/kg) effects good relaxation conditions in burned patients, with an onset time similar to that in controls. This finding contrasts with the response seen with other nondepolarizing drugs, higher doses of which are required to effect paralysis. The decreased metabolism of mivacurium, resulting from depressed plasma cholinesterase activity, probably counteracts the receptor-mediated potential for resistance. Because succinylcholine is contraindicated in burned patients, larger doses of nondepolarizing agents are advocated to effect rapid onset of paralysis. This generalization does not hold for mivacurium. diatrics; plasma cholinesterase; relaxant resistance; succinylcholine, alternative to.)

Topics: Body Weight; Burns; Child; Child, Preschool; Cholinesterases; Electric Stimulation; Female; Humans; Infusions, Intravenous; Isoquinolines; Male; Mivacurium; Muscle Relaxation; Neuromuscular Nondepolarizing Agents; Ulnar Nerve

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.. Thirty adults with 35 (13)% [mean (sd)] burn were studied at 5-91 post-burn days and 31 non-burns matched controls. Mivacurium 0.2 mg kg(-1) was administered as a single bolus. Neuromuscular block was monitored with single-twitch response using TOF-Watch™. Onset time (drug administration to maximal twitch suppression) and spontaneous recovery were measured.. Onset time was significantly prolonged in burns when compared with non-burns (115 vs 90 s; P<0.001). The PChE levels were lower in burns [1432 (916) vs 2866 (731) IU litre(-1); P<0.001] and the neuromuscular recovery to 50% of baseline twitch height was prolonged in burns (41 vs 26 min; P<0.001). There was a significant correlation between PChE and time to 50% recovery for the whole group together (r=-0.6; P<0.001). The dibucaine numbers were not different.. The prolonged onset time suggests resistance to neuromuscular effects, whereas the prolonged recovery suggests increased sensitivity. This divergent response can be explained by qualitative and quantitative changes in acetylcholine receptor expression causing resistance and decreased PChE activity causing sensitivity. Despite using a relatively large dose of mivacurium (0.2 mg kg(-1)) in the presence of decreased PChE levels, this did not overcome the resistance resulting from up-regulated receptors.

Topics: Adolescent; Adult; Burns; Butyrylcholinesterase; Case-Control Studies; Electric Stimulation; Female; Humans; Isoquinolines; Male; Middle Aged; Mivacurium; Neuromuscular Junction; Neuromuscular Nondepolarizing Agents

Burned patients demonstrate resistance to the effects of non-depolarizing blocking drugs as a result of acetylcholine receptor changes. They also have decreased activity of plasma cholinesterase (PCHE), which metabolizes mivacurium. We hypothesized that decreased PCHE activity would decrease metabolism of mivacurium, and counteract the receptor-related resistance following burns.. Thirteen burned patients and six controls, aged 13-18 yr were followed in 27 studies. The burned patients were sub-classified as having 10-30% or >30% body surface area burn and were studied whenever possible at < or =6 days, and at 1-12 weeks after the burn. Mivacurium pharmacodynamics were examined following a bolus (0.15 mg kg(-1)) dose, and during and after a continuous infusion.. Following a bolus, the onset time and the maximal effect were similar to controls. Recovery was prolonged in the 10-30% burn group at 1-12 weeks (P<0.008), with a similar trend in the >30% burn group at < or =6 days (P<0.082) compared with controls. The infusion requirements for mivacurium were not increased in the burned groups. The PCHE activity was decreased in all burn groups and was inversely related to recovery following the bolus (r=0.73, P<0.001) and the infusion (r=0.69, P<0.001).. In contrast to previous studies with non-depolarizers in burned patients, normal mivacurium doses can produce paralysis, at least as rapidly as in controls, but with a possibility of a prolonged recovery from block. The standard dose of mivacurium in the presence of decreased PCHE activity is in effect, a relative overdose that explains the above findings. Mivacurium is an effective drug for use in burns, irrespective of time after, or magnitude of burn injury.

Topics: Adolescent; Burns; Cholinesterases; Drug Administration Schedule; Female; Humans; Isoquinolines; Male; Mivacurium; Neuromuscular Junction; Neuromuscular Nondepolarizing Agents

The pharmacodynamics of mivacurium, a new short-acting non-depolarizing muscle relaxant, were studied in nine severely burned patients with concomitant inhalation injury. Complete neuromuscular blockade was achieved within 1.3 min (controls 3.0 min) following the usually recommended intubating dose (0.15 mg/kg/BW 2 x ED95) of mivacurium. The clinical duration of neuromuscular blockade and the recovery times were slightly prolonged, due to significantly reduced serum cholinesterase activity (clinical duration 24.6 min vs. 15.3 min). This pharmacodynamic profile makes mivacurium preferable for intermittent on-demand neuromuscular blockade in the severely burned patient.

Topics: Adult; Blood Pressure; Burns; Burns, Inhalation; Female; Heart Rate; Humans; Isoquinolines; Male; Mivacurium; Neuromuscular Junction; Neuromuscular Nondepolarizing Agents; Respiration; Skin