Anesthesia and analgesia
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Anesthesia and analgesia · Jun 1998
Comparative StudyRapid development of tolerance to analgesia during remifentanil infusion in humans.
Studies in experimental animals have demonstrated a rapidly developing acute tolerance to the analgesic effect of opioids administered by continuous i.v. infusion. The aim of the present study was to determine whether acute tolerance plays an important role in the analgesic effect of remifentanil provided by i.v. infusion to humans. The analgesic effect of remifentanil, infused at a constant rate of 0.1 microg x kg(-1) x min(-1) for 4 h, was evaluated by measuring pain tolerance with thermal (2 degrees C water) and mechanical (pressure) noxious stimulations in 13 paid volunteers. The constant-rate infusion of remifentanil resulted in a threefold increase in pain tolerance with both tests. After reaching its maximum in 60-90 min, the analgesic effect of remifentanil began to decline despite the constant-rate infusion, and after 3 h of infusion, it was only one fourth of the peak value. A comparative rate in the development of acute tolerance measured in terms of time to 50% recovery during infusion was 129 +/- 27 min (mean +/- SD) with the cold water test and 138 +/- 39 min with the pressure test. We conclude that the development of tolerance should be included in the calculations for target-controlled infusions. ⋯ Our study shows that tolerance to analgesia during remifentanil infusion is profound and develops very rapidly. The administration of opioids during anesthesia based on target-controlled infusions should include corrections for the development of tolerance.
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Anesthesia and analgesia · Jun 1998
0.45% saline and 5% dextrose in water, but not 0.9% saline or 5% dextrose in 0.9% saline, worsen brain edema two hours after closed head trauma in rats.
In this study, we examined the effect of four i.v. fluids (250 mL/kg) on blood glucose and osmolality and brain tissue specific gravity after closed head trauma (CHT) in rats. CHT was delivered at Time 0; blood was sampled at 60 min; fluid infusion began at 75 min and ended at 105 min. Blood was again sampled at 105 and 120 min, and brain tissue specific gravity was determined at 120 min. Five groups (one control and four fluid-treated groups) received CHT, and five other groups (one control and four fluid-treated) did not (n = 9 in each group). 0.45% saline (1/2 NS) and 5% dextrose in water (D5W) accentuated the decrease of brain tissue specific gravity (1.0366 +/- 0.0025 and 1.0368 +/- 0.0028, respectively; mean +/- SD) caused by CHT (1.0395 +/- 0.0036), but 5% dextrose in 0.9% saline (D5NS) and 0.9% saline (NS) did not (1.0431 +/- 0.0042 and 1.0389 +/- 0.0049, respectively). In addition, 1/2 NS decreased blood osmolality (248 +/- 6 mOsm/L), D5W increased blood glucose (1095 +/- 173 mg/dL), D5NS increased blood osmolality (350 +/- 5 mOsm/L) and glucose (1695 +/- 76 mg/dL), and NS caused no significant change. We conclude that administering hypoosmolar i.v. fluids after CHT causes a significant worsening of cerebral edema 2 h after CHT. ⋯ We previously reported worse neurological outcome and/or mortality after closed head trauma in rats when 5% dextrose in water or 0.45% saline was given i.v. compared with 0.9% saline or 5% dextrose in 0.9% saline. The present results and our previous findings indicate that worsening of outcome after closed head trauma in rats may be caused more by edema formation than by hyperglycemia.
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Anesthesia and analgesia · Jun 1998
Comparative StudyThe pharmacokinetics of vecuronium in male and female patients.
To evaluate the effect of gender on the pharmacokinetics of vecuronium, we studied 30 patients (15 male and 15 female) undergoing elective plastic surgery with anticipated surgical blood loss of <300 mL under general anesthesia. General anesthesia was induced with thiopental 4-6 mg/kg and fentanyl 2-4 microg/kg and was maintained with 60% nitrous oxide in oxygen and an end-tidal concentration of 1.5%-2% enflurane. After a 2-min infusion of vecuronium 100 microg/kg, a modified fluorometric assay was used to determine the plasma concentrations of vecuronium for 5 h. The results showed that, compared with women, the plasma concentrations of vecuronium in men were significantly lower during the first 20 min and that the disposition kinetics of vecuronium can be best described mathematically by a three-compartment open model in the two groups. The volume of the central compartment and the volume of distribution at steady state were 39.6 +/- 8.6 and 164.8 +/- 29.3 mL/kg, respectively, in women. These values increased significantly to 54.4 +/- 14.4 and 201.4 +/- 75.8 mL/kg in men (P < 0.05). When the data were calculated on the basis of ideal body weight, the volume of distribution of vecuronium was also different between men and women (P < 0.05. The half-lives of fast distribution and distribution, the elimination half-life, mean residual time, area under the plasma-concentration curve, and plasma clearance were not different between the two groups. We conclude that the pharmacokinetics of vecuronium are significantly different between genders and that and men have the greater volume of distribution of vecuronium. ⋯ The authors found that, compared with women, men had lower plasma concentrations of vecuronium after the i.v. administration of vecuronium and a larger volume of distribution of vecuronium. The pharmacokinetic differences may be related to the differences in the sensitivity to vecuronium between genders.
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Anesthesia and analgesia · Jun 1998
The effect of rate of administration on brain concentrations of propofol in sheep.
A marked reduction in the dose of propofol required to achieve the onset of anesthesia with slower administration rates has previously been reported, but the mechanism of this phenomenon is unclear. We used a chronically instrumented sheep preparation to examine the effects of different administration rates of propofol on its distribution in the brain using mass balance principles to calculate brain concentrations. The administration of 100 mg of propofol i.v. at rates of 200, 50, and 20 mg/min had minimal effect on both the peak brain concentrations of propofol and the total amount of drug entering the brain. The more rapid administration rates increased the rate of uptake into the brain but resulted in large increases in peak arterial blood propofol concentrations. These faster administration rates have previously been associated with high arterial propofol concentrations and an increased risk of hypotension. Simulation of titration to an end point revealed that the dose sparing previously reported at induction with slow administration rates relates only to improved titration to effect, and does not result in more anesthesia for a given dose. Therefore, we conclude that the administration of propofol over 2 min provides a reasonable rate of induction and improved titration to effect, yet avoids excessively high arterial concentrations. ⋯ Alterations in the rate of administration of propofol in sheep have been shown to have little effect on the quantity of propofol delivered to the brain. At induction of anesthesia, administration rates of approximately 50 mg/min seem likely to provide improved titration to effect without excessively prolonging induction.
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Anesthesia and analgesia · Jun 1998
The effect of pneumoperitoneum on intraocular pressure in rabbits with alpha-chymotrypsin-induced glaucoma.
Increased intraperitoneal pressure is associated with physiological changes including alterations of intraocular pressure (IOP). We have previously shown that IOP is not adversely affected by increased intraperitoneal pressure up to 15 mm Hg in women with no preexisting eye disease. The aim of this study was to measure IOP changes associated with increased intraperitoneal pressure (up to 15 mm Hg) of 2 h duration in 12 rabbits with alpha-chymotrypsin-induced glaucoma. A reliable model of glaucoma was created by injecting alpha-chymotrypsin into the posterior chamber of the right eye in 12 rabbits. Thereafter, 5 of the 12 rabbits with glaucomatous eyes were treated with topical timolol. The left eye was used as a control. During pentobarbital general anesthesia, increased intraperitoneal pressure up to 15 mm Hg was created by intraperitoneal CO2 insufflation. Body temperature and expired CO2 were kept constant throughout the study. IOP measurements were made using an electronic pneumotonometer. IOP, mean arterial pressure, heart rate, and central venous pressure were recorded in head-up and head-down positions before, during, and after increased intraperitoneal pressure. The IOP of both eyes, in both treated and untreated rabbits, increased significantly from baseline only when increased intraperitoneal pressure associated with the head-down position resulted in a significant increase in central venous pressure. However, the IOP increase remained within the diurnal range. The major finding of this study is that, in a reliable model of glaucoma, CO2 pneumoperitoneum was associated with an increase in IOP when a head-down position was combined with pneumoperitoneum. ⋯ In rabbits with alpha-chymotrypsin-induced glaucoma, increased intraperitoneal pressure (up to 15 mm Hg) resulted in a significant intraocular pressure increase when pneumoperitoneum was associated with the head-down position. However, the intraocular pressure increase remained within the diurnal range.