Anesthesia and analgesia
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Anesthesia and analgesia · Apr 1998
Comparative StudyComparison of ketamine and dextromethorphan in potentiating the antinociceptive effect of morphine in rats.
We compared the efficacy of two clinically available drugs with N-methyl-D-aspartate receptor antagonist properties, dextromethorphan and ketamine, in potentiating morphine-induced antinociception. Ketamine alone at 0.3-3 mg/kg had no effect on the hot plate test and at 10 mg/kg caused sedation/motor deficits. The antinociceptive effect of 5 mg/kg morphine was slightly enhanced by 1 mg/kg, but not 0.3 or 3 mg/kg, ketamine. Dextromethorphan alone at 45 mg/kg had no effect, but at 60 mg/kg caused sedation/motor deficit. At 15-45 mg/kg, dextromethorphan significantly and dose-dependently increased the magnitude and duration of morphine-induced antinociception. Dextromethorphan also potentiated morphine at doses that, by themselves, did not cause antinociception (1-2 mg/kg). ⋯ Dextromethorphan was more effective than ketamine in potentiating morphine-induced antinociception. Dextromethorphan may thus be the drug of choice for testing the interactions between N-methyl-D-aspartate antagonists and morphine clinically.
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Anesthesia and analgesia · Apr 1998
The relationship of soluble adhesion molecule concentrations in systemic and jugular venous serum to injury severity and outcome after traumatic brain injury.
Adhesion molecules control the migration of leukocytes into tissue after injury. This may result in further cellular damage. We hypothesized that altered serum concentrations of soluble intercellular adhesion molecule (sICAM)-1 and soluble L-selectin (sL-selectin) after traumatic brain injury would correlate with injury severity and neurological outcome. We investigated serum concentrations of sICAM-1 and sL-selectin in 22 patients with traumatic brain injury admitted to the intensive care unit. The Glasgow Coma Scale (GCS) score and Injury Severity Score were recorded. Paired arterial and jugular venous blood samples were taken on admission and 24, 48, and 96 h after injury. Mean systemic and jugular venous concentrations of sICAM-1 were normal on admission but became significantly increased by 96 h (P = 0.018). sL-selectin concentrations of injured patients were markedly below those of controls at all time points (P < 0.001). There were no significant differences between jugular venous and arterial concentrations of either sICAM-1 or sL-selectin. Serum sICAM-1 was significantly related to neurological outcome (P < 0.001) and to the GCS score (P < 0.001). These changes in adhesion molecule expression after acute brain injury may be important in the pathophysiology of secondary injury. The highly significant relationship between serum sICAM-1 and neurological outcome suggests that the inflammatory response to injury may be detrimental. Drugs that antagonize the actions of the adhesion molecules may have a role in therapy after traumatic brain injury. ⋯ This observational study shows that there is a strong association between soluble intercellular adhesion molecule-1 in serum and poor neurological outcome after traumatic brain injury. This suggests that inflammation after brain injury may worsen the prognosis and that therapies directed against this inflammation may prove useful.
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Anesthesia and analgesia · Apr 1998
Chloral hydrate sedation: the additive sedative and respiratory depressant effects of nitrous oxide.
The combination of chloral hydrate and nitrous oxide (N2O) is often used for sedation in pediatric dentistry. The purpose of this study was to determine the extent to which N2O increases the level of sedation and respiratory depression in children sedated with chloral hydrate. Thirty-two children, 1-9 yr, received chloral hydrate, 70 mg/kg (maximum 1.5 g), and then received N2O (30% and 50%). Hypoventilation (maximal PETCO2 > 45 mm Hg) occurred in 23 (77%) children during administration of chloral hydrate alone, in 29 (94%) breathing 30% N2O (P = 0.08 versus control), and in 29 (97%) breathing 50% N2O (P = 0.05 versus control). Mean PETCO2 was increased during 30% (P = 0.007) and 50% (P = 0.02) N2O administration. Using chloral hydrate alone, 8 (25%) children were not sedated, 10 (31%) were consciously sedated, and 14 (44%) were deeply sedated. Using 30% N2O, 2 children (6%) were not sedated, 0 were consciously sedated, and 29 (94%) were deeply sedated (P < 0.0001). Using 50% N2O, 1 child (3%) was not sedated, 0 were consciously sedated, 27 (94%) were deeply sedated, and 1 (3%) had no response to a painful stimulus (P < 0.0001). We conclude that the addition of 30% or 50% N2O to chloral hydrate often causes decreases in ventilation and usually results in deep, not conscious, sedation in children. ⋯ Pediatric sedation in the dental office often consists of nitrous oxide (N2O) after chloral hydrate premedication. We found that the addition of 30% or 50% N2O to chloral hydrate often causes decreases in ventilation and usually results in deep, not conscious, sedation in children.
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Anesthesia and analgesia · Apr 1998
Comparative StudyAntinociceptive potentiation and attenuation of tolerance by intrathecal co-infusion of magnesium sulfate and morphine in rats.
N-methyl-D-aspartate (NMDA) antagonists, such as MK801, delay the development of morphine tolerance. Magnesium, a noncompetitive NMDA antagonist, reduces postoperative morphine requirements. The present study was designed to evaluate the effects of intrathecal co-administration of magnesium sulfate with morphine on antinociceptive potentiation, tolerance, and naloxone-induced withdrawal signs. Magnesium sulfate (40-60 microg/h) co-administration for 7 days, similar to MK801 (10 nmol/h), prevented the decline in antinociceptive response compared with morphine (20 nmol/h). Magnesium sulfate (60 microg/h) produced no antinociception, but co-infused with morphine (1 nmol/h), it resulted in potentiated antinociception compared with morphine throughout the 7-day period. Probe morphine doses after 7-day infusions demonstrated a significantly greater 50% effective dose value for morphine 1 nmol/h (109.7 nmol) compared with saline (10.9 nmol), magnesium sulfate 60 microg/h (10.9 nmol), and magnesium sulfate 60 microg/h plus morphine 1 nmol/h (11.2 nmol), which indicates that magnesium had delayed morphine tolerance. Morphine withdrawal signs after naloxone administration were not altered by the co-infusion of magnesium sulfate. Cerebrospinal fluid magnesium levels after intrathecal magnesium sulfate (60 microg/h) for 2 days increased from 17.0 +/- 1.0 microg/mL to 41.4 +/- 23.6 microg/mL, although serum levels were unchanged. This study demonstrates antinociceptive potentiation and delay in the development of morphine tolerance by the intrathecal coinfusion of magnesium sulfate and morphine in the rat. ⋯ The addition of magnesium sulfate, an N-methyl-D-aspartate antagonist, to morphine in an intrathecal infusion provided better analgesia than morphine alone in normal rats. These results suggest that intrathecal administration of magnesium sulfate may be a useful adjunct to spinal morphine analgesia.