Anesthesia and analgesia
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Anesthesia and analgesia · Jun 2004
Safety of continuous intrathecal midazolam infusion in the sheep model.
We investigated the safety of midazolam administered by continuous intrathecal infusion in relevant animal models. Preservative-free midazolam was delivered to sheep and pigs by using implanted infusion systems (SynchroMed pumps plus silicone catheters). Sheep received midazolam 5 mg/d (n = 4) or 15 mg/d (n = 7) or saline (n = 2) for 43 days at 125 micro L/h. One sheep received 10 mg/d. Infusion concentrations ranged from 1.7 to 2.5 mg/mL (5 mg/d) and from 2.5 to 5.0 mg/mL (15 mg/d). Pigs were evaluated for toxicity only and received 15 mg/d (n = 2) or saline (n = 1) for 43 days at 125 micro L/h. Behavior, neurologic function, and vital signs were documented. Serum and cerebrospinal fluid chemistry and cytology were evaluated, and histology was performed on spinal cord tissue. Behavior and neurologic function remained normal in all subjects. Gross and microscopic evaluation of spinal tissue revealed mild inflammation surrounding the catheter tract in both the midazolam-treated and the saline-treated groups. This inflammation was likely attributable to the mechanical presence of the catheter. These data demonstrate that continuous intrathecal infusion of preservative-free midazolam at doses up to 15 mg/d were well tolerated. ⋯ We investigated the toxicity of preservative-free intrathecal midazolam delivered continuously via implanted infusion systems in sheep and pigs. Doses of 5-15 mg/d were well tolerated. The lack of neurotoxicity observed suggests that intrathecal midazolam may be an alternative for the treatment of intractable pain that is unresponsive to opioids.
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Anesthesia and analgesia · Jun 2004
Enhanced vasodilatory responses to milrinone in catecholamine-precontracted small pulmonary arteries.
Beta-adrenergic agonists (e.g., epinephrine [E] and norepinephrine [NE]) and phosphodiesterase-III inhibitors (e.g., milrinone) are often used in combination to augment ventricular function in the perioperative period. In the myocardium, milrinone acts synergistically with beta-adrenergic agonists to increase contractility. However, the potential interaction between catecholamines with combined alpha- and beta-adrenergic activity and milrinone in the pulmonary circulation has not been determined. We evaluated the vasodilatory effects of milrinone and nitroglycerine on large elastic and small muscular porcine pulmonary vascular rings precontracted with catecholamines with beta-adrenergic agonist activity (E and NE), the alpha-adrenergic agonist phenylephrine, and a nonadrenergic agonist, the thromboxane analog U46619. In small pulmonary arteries, the vasorelaxation with milrinone was significantly enhanced in rings precontracted with E or NE compared with those precontracted with phenylephrine or U46619. However, in large pulmonary arteries, the vasorelaxation with milrinone was similar in all vessel rings and was not influenced by the agonist used to induce precontraction. In marked contrast, the vasorelaxant responses to nitroglycerine were not altered by the specific agonist used for precontraction in either small or large pulmonary vascular rings. Thus, the pulmonary vascular effects of milrinone are enhanced when combined with drugs with beta-adrenoreceptor agonist activity. The vasodilatory interactions exhibited by phosphodiesterase-III inhibitors and the catecholamines NE and E suggest that their combined use might be beneficial in circumstances in which ventricular dysfunction and increased pulmonary vascular resistance occur. ⋯ This study demonstrated that milrinone had enhanced vasodilator effects when combined with drugs with beta-adrenoreceptor agonist activity in small pulmonary artery segments removed from pigs.
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Anesthesia and analgesia · Jun 2004
Case ReportsThe use of dexmedetomidine to facilitate opioid and benzodiazepine detoxification in an infant.
Prolonged use of opioids and benzodiazepines for the care of critically ill infants and children can generate physical dependence. We present a case of an 8-mo-old infant with Hunter's syndrome who was maintained on very large doses of fentanyl and midazolam and who could not be weaned from these drugs by conventional taper. We used dexmedetomidine, an alpha(2)-adrenergic agonist, to facilitate opioid and benzodiazepine withdrawal. A processed electroencephalogram (Bispectral Index) was used to guide the titration of dexmedetomidine in this neurologically impaired infant. This is the first report of this drug being used in an infant to manage chemical dependence withdrawal. ⋯ Dexmedetomidine was used to facilitate opioid and benzodiazepine withdrawal in an 8-mo-old infant. A processed electroencephalogram (Bispectral Index) was used to guide the titration of dexmedetomidine in this neurologically impaired infant. This is the first report of dexmedetomidine use in an infant to manage chemical dependence withdrawal.
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Anesthesia and analgesia · Jun 2004
A platelet activating factor receptor antagonist inhibits cytokine production in human whole blood by bacterial toxins and live bacteria.
We previously reported that a platelet-activating factor receptor (PAFR) antagonist (TCV-309) suppressed lipopolysaccharide (LPS)-induced mortality and tumor necrosis factor (TNF) production in mice. However, the effect of TCV-309 on cytokine production induced by Staphylococcus enterotoxin B (SEB) or live bacteria has not been reported. In this study we investigated the effect of TCV-309 on cytokine production in human whole blood induced by LPS, SEB, and both Gram-positive and -negative bacteria. Human whole blood diluted 5:1 (980 microL) was placed in the wells of a 24-well plate. Ten microliters of LPS, SEB, Escherichia coli O18 K(+), or Staphylococcus aureus were added to each well. After incubation at 37 degrees C for 6 h, TNF, interleukin (IL)-6, and IL-8 in the culture medium were measured. TCV-309 did not affect the growth of either E. coli or S. aureus bacteria in the culture medium for the 6 h incubation. LPS, SEB, and both E. coli and S. aureus induced TNF, IL-6, and IL-8 in human whole blood. TCV-309 significantly inhibited the production of TNF, IL-6, and IL-8 induced by LPS, SEB, and bacteria. A PAFR antagonist suppressed cytokine production induced by LPS, SEB, and both Gram-positive and -negative bacteria in human whole blood. A PAFR plays an important role of producing proinflammatory cytokines induced by both toxins and live bacteria. ⋯ The platelet-activating factor receptor plays an important role in producing proinflammatory cytokines induced by bacterial toxins, such as lipopolysaccharide,Staphylococcus enterotoxin B, and live Gram-positive and Gram-negative bacteria.
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Anesthesia and analgesia · Jun 2004
Simultaneous determination of neuromuscular blockade at the adducting and abducting laryngeal muscles using phonomyography.
Phonomyography (PMG) is a new method for measuring neuromuscular blockade (NMB) at the larynx. In this study, we used PMG to compare NMB at the posterior cricoarytenoid (PCA) and the lateral cricoarytenoid muscle (LCA) in humans. Twelve patients were included in this study. Endotracheal intubation was performed without aid of neuromuscular blocking drugs. One small condenser microphone was inserted beside the vocal cords into the muscular process at the base of the arytenoid cartilage to record acoustic responses of the LCA (vocal cord adduction), and a second microphone was placed behind the larynx to measure NMB of the PCA (vocal cord abduction). Stimulation of the recurrent laryngeal nerve was performed using superficial electrodes placed at the neck (midline between jugular notch and cricoid cartilage) using train-of-four (TOF) stimulation every 12 s. After supramaximal stimulation, mivacurium 0.1 mg/kg was injected and onset, peak effect, and offset of NMB measured and compared using t-test (P < 0.05). The data are presented as mean (SD). Peak effect, onset time, and early recovery to 25% of control twitch height were not significantly different between PCA and LCA at 86% (13) versus 78% (16), 2.3 min (0.45) versus 2.3 min (1.0), and 9.55 min (3.05) versus 8.5 min (4.7), respectively. However, recovery to 75%, 90% of control twitch height, and recovery to a TOF ratio of 0.8 were significantly longer at the PCA than at the LCA at 14 min (4) versus 11 min (5), 17 min (5) versus 11.8 min (5.6), and 17.5 min (5.6) versus 12.3 min (5.5), respectively. The authors conclude that recovery of NMB at the PCA takes longer than at the LCA in humans after mivacurium. ⋯ After neuromuscular blockade in humans, the recovery of the ability to open the vocal cords takes longer than the ability to close the vocal cords.