Anesthesia and analgesia
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Anesthesia and analgesia · Jan 1998
Gabapentin reverses the allodynia produced by the administration of anti-GD2 ganglioside, an immunotherapeutic drug.
Systemically administered, the anti-GD2 antibody produces allodynia demonstrated by decreased mechanical withdrawal threshold. Electrophysiologic recordings indicate a probable neuropathic origin, as small-diameter sensory fibers develop continuous high-frequency discharge after antibody administration. Gabapentin (GBP) is a gamma-aminobutyric acid analog originally synthesized for its anticonvulsant actions. Several open-label clinical studies, as well as a wealth of anecdotal evidence, suggest that GBP may be beneficial for the treatment of neuropathic pain. This study examined the effects of GBP given as a posttreatment after induction of an anti-GD2-associated allodynia. Anti-GD2 (1 mg/kg intravenously [i.v.]) administered to Sprague-Dawley rats reduced the mean withdrawal threshold from 14.71 to 4.95 g (P < 0.001), as measured by using von Frey hairs. This was reversed by GBP in a dose-dependent fashion; the minimal effective dose was between 3 and 30 mg/kg i.v. The maximal percent analgesic effect of GBP was 76% and 93% at doses of 30 and 100 mg/kg, respectively (P < 0.001). With these doses, side effects were minimal and were manifested as slightly decreased spontaneous movement and startle response. No changes were seen in reflex responses to corneal or pinna stimulation, and no motor deficits were observed. These data support the use of GBP as an effective therapy for neuropathic pain. ⋯ After the administration of anti-GD2 antibody, rats display an escape reaction to light touch, increased blood pressure, and aberrant firing in nerve fibers associated with pain transmission. Systemic gabapentin reduced or eliminated the escape response and reversed the hypertension with minimal side effects. This suggests that gabapentin blocked the antibody-associated (neuropathic) pain.
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Anesthesia and analgesia · Jan 1998
Prolonged inhaled NO attenuates hypoxic, but not monocrotaline-induced, pulmonary vascular remodeling in rats.
In concentrations of 10-20 ppm, inhaled nitric oxide (NO) decreases pulmonary artery pressure and attenuates vascular remodeling in pulmonary hypertensive rats. Because NO is potentially toxic, it is important to know whether lower concentrations attenuate vascular remodeling produced by different etiologies. Therefore, we determined the effects of prolonged, small-dose inhaled NO administration on hypoxic and monocrotaline (MCT)-induced pulmonary vascular remodeling. Rats were subjected to normoxia, hypoxia (normobaric 10% oxygen), or hypoxia plus NO in concentrations of 50 ppb, 200 ppb, 2 ppm, 20 ppm, and 100 ppm for 3 wk. A second group of normoxic rats was given MCT (60 mg/kg intraperitoneally) alone or in the presence of 2, 20, and 100 ppm of NO. Subsequently, pulmonary artery smooth muscle thickness and the number of muscular arteries (percentage of total arteries) were determined. Right ventricular hypertrophy was determined by right to left ventricle plus septum weight ratio (RV/LV + S). Pulmonary artery smooth muscle thickness and the percent muscular arteries were increased by hypoxia and MCT. The hypoxic increase in thickness was attenuated by all concentrations of NO, with 100 ppm being greatest, whereas NO had no effect on MCT rats. NO attenuated the increase in percent muscular arteries in hypoxic but not MCT rats. The RV/LV + S was increased by hypoxia and MCT compared with normoxia. Hypoxia-induced RV hypertrophy was decreased by all concentrations of inhaled NO, although attenuation with 50 ppb was less than with 200 ppb, 20 ppm, and 100 ppm. In MCT rats 2 and 100 ppm NO increased RV hypertrophy, whereas 20 ppm had no effect. In conclusion, inhaled NO in concentrations as low as 50 ppb attenuates the pulmonary vascular remodeling and RV hypertrophy secondary to hypoxia. In contrast, concentrations as high as 100 ppm do not attenuate MCT-induced pulmonary remodeling. These results demonstrate that extremely low concentrations of NO may attenuate remodeling but that the effectiveness is dependent on the mechanism inducing pulmonary remodeling. ⋯ The authors determined whether inhaled NO, a selective pulmonary vasodilator, attenuates pulmonary vascular remodeling caused by two models of pulmonary hypertension: chronic hypoxia and monocrotaline injection. Analysis of pulmonary vascular morphology suggests that very low concentrations of NO effectively attenuate hypoxic remodeling but that NO is not effective in monocrotaline-induced pulmonary remodeling.
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Anesthesia and analgesia · Jan 1998
The inhibitory effects of thiopental, midazolam, and ketamine on human neutrophil functions.
We investigated the effect of thiopental, midazolam, and ketamine (at clinically relevant concentrations and at 0.1 and 10 times these concentrations) on several aspects of human neutrophil functions. The three intravenous (i.v.) anesthetics significantly decreased chemotaxis, phagocytosis, and reactive oxygen species (ROS) (O2-, H2O2, OH) production of neutrophils in a dose-dependent manner. At clinically relevant concentrations, thiopental and midazolam significantly depressed these neutrophil functions. However, ketamine at the clinical plasma concentration did not impair chemotaxis or ROS production, except phagocytosis. In contrast, the three anesthetics had no effect on the levels of ROS production by a cell-free ROS generating system. In addition, intracellular calcium concentrations in neutrophils stimulated by N-formyl-L-methionyl-L-leucil-L-phenylalanine were dose-dependently decreased in the presence of each of the three anesthetics. The suppression of an increase in intracellular calcium concentrations may be responsible for the inhibition of neutrophil functions by the i.v. anesthetics. ⋯ Neutrophils play an important role in the antibacterial host defense system and autotissue injury. We found that thiopental and midazolam (but not ketamine), at clinically relevant concentrations, impaired the neutrophil functions.
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Anesthesia and analgesia · Jan 1998
In rats breathing from a nonrebreathing system, substitution of desflurane for isoflurane toward the end of anesthesia incompletely restores the time of recovery toward that of desflurane.
The lower solubility of desflurane allows a more rapid emergence from anesthesia than after anesthesia with the more soluble but less expensive anesthetic, isoflurane. Some practitioners use isoflurane for maintenance of anesthesia, crossing over to desflurane later in maintenance in an attempt to combine the cost-effectiveness of isoflurane with the rapid emergence from desflurane. We hypothesized that this maneuver would not accomplish its goals. Twenty-four male Sprague-Dawley rats received 1.2 minimum alveolar anesthetic concentration (MAC) of desflurane for the final 15, 30, or 60 min of a 2-h, 1.2-MAC isoflurane anesthetic in a nonrebreathing anesthesia system. We measured the time from cessation of anesthetic administration to the time each rat righted himself twice. Immediately after righting for the second time, we tested each rat's ability to remain atop a rotating rod (Rota-Rod) for 60 s continuously. Early (righting reflex) and late (Rota-Rod) recovery occurred more rapidly (P < 0.001) after 120 min of anesthesia with desflurane alone than after 120 min of anesthesia with isoflurane alone. A cross-over period of 30 min or longer produced a righting reflex time that did not differ from that found with desflurane alone, but a 15-min cross-over did not. Progressively longer cross-over periods led to proportionally better Rota-Rod performance, but no cross-over duration produced the rapidity of recovery seen with desflurane alone. We concluded that in a nonrebreathing system, switching to desflurane during the last 30 min of anesthesia substantially improved early recovery but produced a much smaller improvement in later recovery. ⋯ The newer inhaled anesthetics offer the advantage of lower solubility, and thus more rapid emergence from anesthesia, than do the older inhaled anesthetics. However, they can be more expensive to use. This study demonstrates that substituting the newer anesthetic, desflurane, toward the end of anesthesia for an older anesthetic of greater solubility, isoflurane, does not produce recovery comparable to that of desflurane alone. Furthermore, this technique can be more costly than using desflurane throughout anesthesia.