Train-of-four Count Research Articles

Sugammadex: A Revolutionary Approach to Neuromuscular Antagonism

Sugammadex: A Revolutionary Approach to Neuromuscular Antagonism

The Quantitative Distinction Between Train-of-Four ???Counts of 2??? and Posttetanic ???Counts of 2??? Evidenced by a Stable Paralysis/Stable Infusion Rate Method in Anesthetized Patients Receiving Mivacurium

In this study we quantitatively evaluated, by a stable paralysis/stable infusion rate method, the difference between two standardized paralysis levels--train-of-four (TOF) count of 2 responses and posttetanic count (PTC) of 2. Ten ASA physical status I-II consenting adult patients scheduled for elective surgery were anesthetized (sufentanil/propofol), tracheally intubated, mechanically normoventilated with a fixed O(2)/air mixture, and normothermic; oropharynx and thenar temperatures were maintained above 36 degrees and 32.5 degrees C, respectively. After partial recovery from 200 microg/kg mivacurium (MIV), stable tactile TOF and PTC counts of 2 paralysis levels were induced on the adductor pollicis muscle by manual adjustments of an infusion pump containing MIV. The paralysis levels and the infusion rates were considered as stable once they remained constant at 4 consecutive time points separated by 5 min each. Infusion rates observed were: TOF count 2-6 (2-11) and PTC 2-17 (3-18) microg . kg(-1) . min(-1) (P < 0.001; Wilcoxon's paired comparison test). Under the present conditions, obtaining and maintaining a PTC of 2 requires MIV infusion rates far in excess of the "standard" recommendations mentioned in the literature for MIV infusion management.

Rapid-Sequence Intubation with Rocuronium

Background: Succinylcholine is still the most frequently used muscle relaxant for rapid-sequence intubation despite its well-known side effects. Rocuronium has been reported to develop a rapid onset of action and may be suitable as a component of a rapid-sequence intubation. The purpose of this study was to compare tracheal intubating conditions by following different rocuronium doses and application techniques versus succinylcholine. Methods: Fifty nine ASA physical status 1 and 2 adult patients scheduled for elective surgeries were anesthetized with thiopental sodium 5 mg/kg and muscle relaxant using a rapid-sequence technique. Group I (n = 12) received succinylcholine 1.0 mg/kg, group II (n = 15) received rocuronium 1.0 mg/kg, group III (n = 16) received rocuronium 0.6 mg/kg as a single bolus dose, and group IV (n = 16) received a priming dose of rocuronium 0.06 mg/kg followed three minutes later by rocuronium 0.54 mg/kg. Intubation was performed 60 seconds after the administration of muscle relaxant and intubating conditions were evaluated by clinical scoring (Table 1), and train-of-four (TOF) count of the adductor pollicis by accelerography. Results: TOF counts of group I were lower than those of groups III and IV, and those of group II were lower than group III (P

Pharmacodynamics and Atracurium and Laudanosine Concentrations during a Fixed Continuous Infusion of Atracurium in Mechanically Ventilated Patients with Acute Respiratory Distress Syndrome

The present study was designed to assess the pharmacodynamics and the plasma levels of atracurium and laudanosine found during a 72-hour fixed rate infusion of atracurium in acute respiratory distress syndrome patients without renal or liver failure. Nine sedated and mechanically ventilated acute respiratory distress syndrome patients without renal or liver failure were paralysed with a bolus of atracurium (1 mg x kg(-1)) followed by a 72-hour continuous infusion (1 mg x kg(-1) x h(-1)). The count of train-of-four (TOF) and TOF ratio were monitored by an accelerograph until full neuromuscular recovery (T4/T1 > or = 0.7). Atracurium and laudanosine concentrations were measured from the onset to four days after cessation of the infusion. An electroencephalogram was recorded daily. Analysis showed that TOF count was always < or = 3 until cessation of the infusion. Following cessation, neuromuscular recovery occurred between 31 and 96 minutes (median value = 45 min). The highest atracurium and laudanosine concentrations ranged from 3.3 to 5.8 microg x ml(-1) and from 3 to 20 microg x ml(-1) respectively. In four patients with renal impairment, the highest laudanosine concentration was > 10 microg x ml(-1). No seizure was recorded. A fixed infusion rate of atracurium in acute respiratory distress syndrome patients provided an effective muscle paralysis with a rapid neuromuscular recovery but can lead to accumulation of laudanosine in patients with renal impairment.

Pharmacokinetics of Atracurium and Laudanosine in Intensive Care Patients with Acute Respiratory Distress Syndrome Undergoing Mechanical Ventilation

Objective: To determine the pharmacokinetic profiles of atracurium and its main metabolite (laudanosine) in patients with acute respiratory distress syndrome undergoing mechanical ventilation. Patients and Methods: Plasma pharmacokinetic profiles of atracurium and laudanosine were studied in eight critically ill patients with acute respiratory distress syndrome who required a neuromuscular blocking drug to assist mechanical ventilation. Patients received an infusion of atracurium (1 mg/kg per hour) for 72 hours after an initial intravenous bolus dose of 1 mg/kg. Neuromuscular blockade was monitored using an accelerograph. Blood samples were obtained over a 96-hour period. Atracurium and laudanosine concentrations in plasma were determined by high performance liquid chromatography A single-compartment pharmacokinetic model was fitted to plasma concentrations of atracurium and laudanosine. Results: For atracurium, the median elimination half-life value was 20.7 minutes (0.35h); the steady-state volume of distribution ranged from 0.148 to 0.327 L/kg and the total clearance from 0.27 to 0.67 L/h/kg (4.5 to 11 ml/min/kg). For laudanosine, the elimination half-life ranged from approximately 2 to 21 hours and the maximum plasma concentration ranged from 0.86 to 16 mg/L. For all patients, the train-of-four (TOF) count was recorded to 4 at baseline. Within 1 hour after the beginning of infusion, 7 of 8 patients had a TOF count of ≤1. The neuromuscular recovery ranged from 32 to 67 minutes. Conclusion: The pharmacokinetic properties of atracurium in intensive care unit patients with acute respiratory distress syndrome are similar to those in patients during anaesthesia. Moreover, the dosage regimen administered to the patients in this study (i) provided sufficient neuromuscular blockage for adequate ventilation, and (ii) does not require monitoring of neuromuscular function, a procedure that does not seem to eliminate prolonged weakness and myopathy.

Prolonged Paralysis After a Test Dose of Mivacurium in a Patient with Atypical Serum Cholinesterase

Prolonged Paralysis After a Test Dose of Mivacurium in a Patient with Atypical Serum Cholinesterase

Residual Postoperative Paralysis

Based on a train-of-four (TOF) ratio greater than 0.70 as the standard of acceptable clinical recovery, undetected postoperative residual paralysis occurs frequently in postanesthesia care units. In most published studies, detailed information regarding anesthetic management is not provided. The authors reexamined the incidence of postoperative weakness after the administration of long- and short-acting neuromuscular blockers because few, if any, such comparative studies are available. Ninety-one adult patients were studied. In group 1 (mivacurium, n = 35), anesthesia was induced with propofol/ fentanyl and maintained with nitrous oxide, desflurane, and opioid supplementation. The response of the adductor pollicis to ulnar nerve stimulation was estimated by palpating the thumb. Mivacurium (0.20 mg/kg) was administered for tracheal intubation, and an infusion was adjusted to maintain the TOF count at 1. When surgery was completed, the infusion was discontinued. When a second twitch could be detected, 7.0 micrograms/kg atropine and then 0.5 mg/kg edrophonium were administered. At 5 and 10 min, the mechanical TOF response was measured. Additional measurements were recorded if possible. Patients were tracheally extubated and discharged from the operating room when they could respond to verbal commands and no TOF fade was palpable. In group 2 (pancuronium-desflurane anesthesia, n = 29), the protocol was identical to that of group 1, except that 0.07 mg/kg pancuronium was administered for tracheal intubation. Additional increments (0.5 to 1 mg) were given as needed. Antagonism was accomplished with 0.05 mg/kg neostigmine and 0.01 mg/kg glycopyrrolate. In group 3 (pancuronium propofol-opioid, n = 27), the protocol was identical to that of group 2, except that anesthesia was maintained with nitrous oxide and a propofol-alfentanil infusion. In all groups, patients were assessed until a TOF ratio of 0.90 or more was achieved. All of the patients in group 1 had TOF ratios greater than 0.80 on arrival in the postanesthesia care unit. Twenty of 35 patients had TOF ratios 0.90 or more while they were still in the operating room. Thirty-three of 35 patients had TOF ratios 0.90 or more within 30 min of reversal, and this value was reached in all patients by 45 min. Recovery parameters in groups 2 and 3 did not differ from each other. Hence data from these groups were pooled. Fifty-four of 56 patients who received pancuronium had TOF values of 0.70 or more, the remaining two patients had values of 0.6 to 0.7. In contrast to the mivacurium group, however, only four patients achieved a TOF ratio of 0.90 or greater while still in the operating room. Finally, eight of these patients did not achieve this degree of recovery within 90 min of reversal. These results suggest that if nondepolarizing neuromuscular blockers are administered using tactile evaluation of the TOF count as a guide, critical episodes of postoperative weakness in the postanesthesia care unit should occur infrequently even with long-acting relaxants. Nevertheless, if full recovery is defined as return to a TOF ratio of 0.90 or more, then short-acting agents would appear to offer a wider margin of safety.

Tactile Evaluation of Train-of-four Count as an Indicator of Reliability of Antagonism of Vecuronium- or Atracurium-induced Neuromuscular Blockade

Recent evidence suggests that edrophonium is not the agent of choice to reverse profound neuromuscular blockade but remains an efficacious drug when the level of neuromuscular blockade to be antagonized is modest. We studied 90 healthy adults in an attempt to address the questions: 1) How much variability in such neuromuscular parameters as single twitch height and the train-of-four (TOF) fade ratio (T4/T1) exist when the TOF count first returns to four palpable responses? 2) Is edrophonium a reliable antagonist at this measured point of recovery? 3) What is the optimal dose of edrophonium needed to produce prompt (less than 10 min) and satisfactory (T4/T1 greater than 0.7) reversal when the fourth response of the thumb to indirect TOF stimulation just becomes palpable? Patients were given a bolus atracurium or vecuronium (n = 45 in each group) followed by an iv infusion sufficient to maintain single twitch as measured by electromyography at 10-15% of control values. At the end of surgery, the infusion was terminated and spontaneous recovery was allowed to begin. Once the tactile TOF count was four, edrophonium 0.3, 0.5, or 0.75 mg/kg was administered. At a count-of-four the first twitch averaged 37% of control (+/- 8.5% standard deviation; pooled data from all groups) and the mean T4/T1 ratio was 0.14 +/- 0.049. After atracurium neuromuscular blockade, edrophonium 0.3 mg/kg produced adequate antagonism in 10 min. At this time the mean T4/T1 ratio was 0.79 +/- 0.07 and the lowest observed value was 0.67. Increasing the edrophonium dose to 0.75 mg/kg accelerated recovery by 4-5 min.(ABSTRACT TRUNCATED AT 250 WORDS)