Anesthesia and analgesia
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Anesthesia and analgesia · Nov 2001
Precurarization and priming: a theoretical analysis of safety and timing.
The priming principle suggests that the onset of neuromuscular block may be accelerated if an intubating dose is preceded by a priming dose administered a few minutes earlier. We thought it would be instructive to use a pharmacodynamic/pharmacokinetic model to estimate the risk associated with different priming doses and intervals. In any normal population, there is wide variability in the response to neuromuscular blocking drugs. For most relaxants, the coefficient of variation for the 50% effective dose (ED(50)) approximates 20%-25%. Thus, 1 patient in 50 (-2.05 SD) may have an ED(50) only half of the commonly cited value. By using published pharmacodynamic/pharmacokinetic data, we calculated the effect of administering 10%, 20%, or 30% of the ED(95) on the response of the adductor pollicis muscle in a population normally distributed with respect to drug sensitivity. A dose equivalent to 10% of the ED(95) will rarely produce a measurable neuromuscular effect. As this dose is increased, the potential for clinical weakness rapidly escalates. In 1 in 50 individuals, the usual recommendation of 10% of the intubation dose will produce measurable neuromuscular depression. For vecuronium, the optimal priming interval is 5 min. The safety and dependability of the priming principle is very much subject to the laws of probability. ⋯ When using the priming principle to accelerate the onset of neuromuscular block, the initial dose should not exceed 10% the drug's ED(95). For drugs other than rocuronium, the optimal priming interval is not <5 min.
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Anesthesia and analgesia · Nov 2001
The interaction between intrathecal neostigmine and GABA receptor agonists in rats with nerve ligation Injury.
Nerve ligation injury may produce a pain syndrome that includes tactile allodynia. Reversal effects on tactile allodynia have been demonstrated after the intrathecal administration of gamma-aminobutyric acid (GABA) receptor agonists or cholinesterase inhibitors in rats. We examined the drug interactions between neostigmine and muscimol or baclofen in a rat model of nerve ligation injury. Rats were prepared with tight ligation of the left L5-6 spinal nerves and chronic intrathecal catheter implantation. Tactile allodynia was measured by applying von Frey filaments ipsilateral to the lesioned hindpaw. Thresholds for paw withdrawal were assessed. Neostigmine (0.3-10 microg), muscimol (0.1-10 microg), and baclofen (0.1-3.0 microg) were administered to obtain the dose-response curve and the 50% effective dose (ED(50)). Fractions of ED(50) values were administered intrathecally to establish the ED(50)s of drug combinations (neostigmine-muscimol and neostigmine-baclofen). The drug interactions were performed. Intrathecal neostigmine, muscimol, baclofen, and their combinations produced a dose-dependent increase in withdrawal threshold of the lesioned hindpaw. Both analyses revealed a synergistic interaction for the neostigmine-muscimol combination, whereas the effect of the neostigmine-baclofen combination was additive. These results suggest that the activation of both muscarinic and GABA(A) receptors is required for synergistic interaction. ⋯ This study indicates that drug interaction is synergistic for the neostigmine-muscimol combination, whereas the effect of the neostigmine-baclofen combination is additive. In a rat model of nerve ligation injury, neostigmine, muscimol, baclofen, and their combinations provide an antagonism on touch-evoked allodynia at the spinal level.
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Anesthesia and analgesia · Nov 2001
A simple apparatus for accelerating recovery from inhaled volatile anesthetics.
Hyperpnea increases anesthetic elimination but is difficult to implement with current anesthetic circuits without decreasing arterial PCO2. To circumvent this, we modified a standard resuscitation bag to maintain isocapnia during hyperpnea without rebreathing by passively matching inspired PCO2 to minute ventilation. We evaluated the feasibility of using this apparatus to accelerate recovery from anesthesia in a pilot study in four isoflurane-anesthetized dogs. The apparatus was easy to use, and all dogs tolerated being ventilated with it. Under our experimental conditions, isocapnic hyperpnea reduced the time to extubation by 62%, from an average of 17.5 to 6.6 min (P = 0.012), but not time from extubation to standing unaided. This apparatus may provide a practical means of applying isocapnic hyperpnea to shorten recovery time from volatile anesthetics. ⋯ A simple modification to a standard resuscitation bag allows one to increase ventilation without decreasing blood carbon dioxide levels. In dogs, we confirmed that this circuit can be used to accelerate the elimination of and recovery from volatile anesthetics.
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Anesthesia and analgesia · Nov 2001
Randomized Controlled Trial Comparative Study Clinical TrialUlnar nerve block induced by the new local anesthetic IQB-9302 in healthy volunteers: a comparison with bupivacaine.
We evaluated the duration of sensory anesthesia after blockade of the ulnar nerve of IQB-9302, a new local amide anesthetic, compared with bupivacaine. A double-blinded, randomized, cross-over study in 12 healthy volunteers aged 18 to 35 yr was performed. Three milliliters of 0.25% IQB-9302 was administered in one wrist and bupivacaine in the other. A week later, the blocks were repeated with a concentration of 0.5%. These concentrations were chosen because they seemed to be equipotent in previous studies. The duration of sensory anesthesia was the main variable measured; secondary outcomes were motor block, time to onset, and time to recovery from block. The duration of sensory block was similar for IQB-9302 and bupivacaine at a concentration of 0.25%; median and range: 409 min (0-800 min) for IQB-9302 and 258 min (0-665 min) for bupivacaine (95% confidence interval for the difference from -47 to 545, P = 0.82, Wilcoxon's test). The results with 0.5% were: 525 min (440-735 min) and 690 min (365-1098 min), respectively (P = 0.026). There were no significant differences in the other variables measured. No important adverse reactions were seen. We conclude that IQB-9302 is an effective new local anesthetic for blockade of ulnar nerve at the concentrations tested. ⋯ IQB-9302 is a new local anesthetic that has shown a long duration of action and low cardiovascular toxicity in preclinical studies. We report the results of a phase I clinical trial to compare this new drug with bupivacaine for ulnar nerve block.
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Anesthesia and analgesia · Nov 2001
Randomized Controlled Trial Clinical TrialEpinephrine does not prolong the analgesia of 20 mL ropivacaine 0.5% or 0.2% in a femoral three-in-one block.
We tested the effect of epinephrine added to 20 mL ropivacaine 0.5% and 0.2% on postoperative analgesia via a femoral catheter after total knee replacement. Forty-one patients undergoing total knee replacement under combined peripheral block/general anesthesia were randomly allocated to two groups. After insertion of a femoral catheter, 21 patients in the Ropivacaine-Epinephrine (ROPI-EPI) group received 20 mL ropivacaine 0.5% plus epinephrine 1:200,000, whereas 20 patients in the Ropivacaine group (ROPI) received 20 mL plain ropivacaine 0.5%. Thereafter, a sciatic block with 30 mL bupivacaine 0.5% plus epinephrine 1:200,000 was performed in all patients, followed by general anesthesia. After surgery, patient-controlled analgesia (PCA) with ropivacaine 0.2% plus epinephrine 1:200,000 for Group ROPI-EPI and plain ropivacaine 0.2% for Group ROPI was available via the femoral catheter (200 mL ropivacaine 0.2% +/- epinephrine, bolus 20 mL, lockout 120 min). The patients were instructed to use PCA when the knee pain score was >3 cm. The interval between the initial ropivacaine injection and the first PCA injection determined the duration of 20 mL ropivacaine 0.5% +/- epinephrine, whereas the interval between the first and second PCA injection determined the duration of 20 mL ropivacaine 0.2% +/- epinephrine. The average duration of ropivacaine 0.5% was 657 +/- 345 min for the ROPI-EPI group and 718 +/- 423 min for the ROPI group (NS), whereas for ropivacaine 0.2%, the average duration was 409 +/- 245 min for the ROPI-EPI group and 419 +/- 339 min for the ROPI group (not significant). We conclude that epinephrine does not influence the duration of analgesia of the ropivacaine concentrations investigated. ⋯ We evaluated the effect of epinephrine on the duration of analgesia of 20 mL ropivacaine 0.5% or 0.2% injected in femoral three-in-one block for pain relief after total knee replacement. Our results show that epinephrine does not alter the duration of analgesia of the two solutions investigated.