[Planned sedation with dexmedetomidine hydrochloride after pediatric cardiac surgery; an institutional experience].

Dexmedetomidine hydrochloride (DEX) is a newly developed alpha-2 adrenergic agonist sedative and has been shown to be effective in post-surgical patients, providing not only unique sedation but also stabilization of hemodynamic and respiratory function. We investigated the hemodynamic and respiratory effects and efficacy of DEX in 84 consecutive patients (age <6 months: 18, 6-12 months: 13, 1-3 years: 29, 4-9 years: 18, >10 years: 5, male:female = 44:40) who were sedated by DEX in combination with a small dose of midazolam and morphine. DEX was commenced at an initial dose of 0.7 microg/kg/hr during surgery, approximately 1 hour prior to transfer to the intensive care unit (ICU). DEX infusion was maintained at a rate of 0.2-0.7 microg/kg/hr after ICU admission throughout weaning from mechanical ventilation and extubation. The dose of the sedatives was optimized by scoring on Ramsay's sedative scale. There were no undesirable hemodynamic changes throughout the DEX infusion. Respiration was maintained and all patients were extubated uneventfully. Optimal level of sedation was achieved in all patients. There were no adverse events related to DEX administration. Moreover, junctional ectopic tachycardia (JET) and severe pulmonary hypertension (PH) leading to clinical deterioration, which are the major causes of postoperative morbidity in pediatric cardiac surgery, occurred at a low incidence in this series. Our DEX protocol provided 1) satisfactory postoperative sedation without compromising hemodynamics and respiration, and 2) prevention and amelioration of postoperative morbidity caused by sympathomimetic stimulation, in pediatric cardiac surgery.

Protective effect of tyrphostin AG-556 on shock induced by endotoxin or gram positive bacteria.

The effects of tyrphostin AG-556 (TYR), a tyrosine kinase inhibitor, were evaluated on shock induced by lipopolysaccharide (LPS) or group B streptococcus (GBS) in rats. Mortality and mean survival time were monitored. Plasma 6-keto prostaglandin F1alpha (6-keto PGF1alpha) was also measured at four hours after LPS injection. The effects of TYR on the production of 6-keto PGF1alpha thromboxane B2(TXB2) and nitrite (NO) from LPS or GBS stimulated in vitro peritoneal rat macrophage were also examined. Salmonella enteritidis LPS (12 mg/kg, i.v. ) (n=6) produced severe shock (100% mortality). Simultaneous treatment with TYR (n=6) significantly (p < 0.01) extended mean survival time and 33% of rats survived. Plasma 6-keto PGF1alpha concentrations were increased in LPS controls, whereas TYR (5 mg/kg) significantly (p < 0.05) decreased the production. Animals treated with GBS/D-galactosamine (n=9) also exhibited shock with 100% lethality and TYR again prolonged survival time (p < 0.05) with 55% of the animals surviving. To evaluate direct effects of TYR on mediator production induced by LPS or GBS, rat macrophages were stimulated with heat-killed GBS or LPS with or without TYR. Supernatants were collected at 24 h for determination of TXB2, 6-keto PGF1alpha and NO. All mediators measured were significantly increased (p < 0.05) with LPS or GBS. TYR inhibited (p < 0.05) the production of all mediators from macrophages induced by LPS or GBS. The decrease in eicosanoids was associated with a reduction of the content of cyclooxygenase-2 (COX-2) as determined by western blotting. Collectively, these results suggest that TYR ameliorates toxic shock induced by LPS or gram positive bacteria. This protection is associated with suppression of macrophage mediator production.

[Effects of fentanyl on renal sympathetic nerve activity, heart rate and systemic blood pressure in anesthetized rabbits--an evaluation in both rabbits and human].

This study was designed to evaluate effects of fentanyl (F) on heart rate (HR), systemic blood pressure (SBP) and renal sympathetic nerve activity (RNA) in urethane- or halothane-anesthetized rabbits. Twenty three urethane-anesthetized rabbits were divided into the following four groups: animals with neuraxis intact (Intact group, N = 8), cervical vagotomized animals (Vagotomy group, N = 5), animals treated with sino-aortic denervation (SAD group, N = 5), and those with sino-aortic denervation with vagotomy (SADV group, N = 5). In the intact group, administration of F (20 micrograms.kg-1, i.v.) caused a significant decrease in HR, but not in SBP, even in the presence of increase in RNA. In the Vagotomy group, no significant alterations in HR and SBP occurred despite activation of RNA. In the SAD group, F caused a significant decrease in HR and an increase in both SBP and RNA. In the SADV group, a decrease in HR disappeared but a significant increase in both SBP and RNA developed. In halothane-anesthetized rabbits having intact baroreceptors (N = 5), similar hemodynamic and sympathetic responses to F were observed. In human (N = 5), F (6 micrograms.kg-1, i.v.) caused a decrease in HR but the effect was not significant on SBP. Thus similar hemodynamic changes occurred in both human and in the animals. These results suggest that F may cause a simultaneous activation of vagal nerve and sympathetic nervous system, which might contribute to the hemodynamic stability when F is administered in human.

Role of vagal afferents in hypotension induced by venous air embolism.

To evaluate the role of the autonomic nervous system in the development of hypotension during air embolism, we studied the effects of an intravenous bolus injection of air (0.5 ml/kg) on mean blood pressure (MBP), central venous pressure (CVP), and renal nerve activity (RNA) in urethan-anesthetized rabbits of three groups: animals with an intact neuraxis (intact group; n = 5), cervical-vagotomized animals (vagotomy group; n = 5), and sinoaortic-denervated animals (SAD group; n = 5). In the intact group, despite a significant decrease in MBP at 10 s after air injection, RNA did not increase from the preinjection level. This response of RNA was associated with a significant increase in CVP and lasted for 20 s after the injection. Vagotomized animals, however, exhibited a significant augmentation in RNA in response to a drop in MBP at 10 s after the injection. In the SAD group, profound declines in both MBP and RNA were observed at 10 s after the injection of air. Animals in these two groups showed remarkable increases in CVP. At 5 min after the air administration, MBP in the vagotomy group was significantly higher than that in the intact group. All animals in the SAD group died within 5 min of the injection. These results indicate that during hypotension induced by air injection, sympathetic activation through arterial baroreceptors may be depressed by vagal afferents emanating from cardiopulmonary receptors; the results also suggest that the arterial baroreceptor nerves may be required to overcome the lethal events that should occur during venous air embolism.

Thyrotropin-releasing hormone produces different hemodynamic effects in vegetative and brain-dead patients.

To define a mechanism for the pressor effects of thyrotropin-releasing hormone (TRH), we evaluated changes in mean blood pressure (MBP) when a synthetic form of TRH (0.1 mg/kg, i.v.) was injected into two types of comatose patients: vegetative and brain dead. The patients in the vegetative group (n = 7, age 58 +/- 6) retained spontaneous respiration and brainstem function, whereas the brain-dead (BD) patients (n = 7, age 68 +/- 4) lacked these functions. In the vegetative group, TRH caused significant increases in MBP (from 91 +/- 8 mm Hg to 110 +/- 10 mm Hg) at 2 min after the injection [p < 0.05, analysis of variance (ANOVA) with a Scheffé F-test]. In contrast, five of the seven BD patient showed no alterations in the measured parameter in response to the TRH injection. However, the remaining two BD patients, who had spinal reflexes, exhibited an elevation in MBP. In such BD patients, baroreceptor reflex function was virtually absent, suggesting that the blood pressure regulation mediating through the baroreceptor reflex system might be abolished. These results indicate that in comatose patients, the hemodynamic effects of TRH may differ depending on impairments in the central nervous system; the results support previous reports indicating a mediation of the central sympathetic nervous system in the development of pressor effects of TRH. Furthermore, because brain-dead patients with spinal reflexes showed hypertensive responses to TRH, there is a possibility that these responses may have resulted from an activation of TRH receptors in the spinal cord.

[Effects of air injection on hemodynamics and sympathetic nerve activity in urethane-anesthetized rabbits].

We designed this experiment to evaluate effects of intravenous bolus injection of air (0.5 ml.kg-1) on systemic blood pressure (SBP), central venous pressure (CVP), and renal nerve activity (RNA) in urethane-anesthetized rabbits. Animals were divided into the following three groups: animals with neuraxis intact (I group, N = 5), cervical vagotomized animals (V group, N = 5) and sinoaortic denervated animals (SAD group, N = 4). All animals were placed on the right-side down position to avoid effects of the posture throughout the experiments of air embolism. In the I group, air caused profound hypotension (from 95 +/- 10 to 54 +/- 15 mmHg) associated with a significant increase in CVP (from 2 +/- 2 to 7 +/- 3 mmHg) twenty seconds after the injection of air. In spite of the significant hypotension, RNA response did not show any increase for twenty seconds. This response was followed by an augmentation in RNA thirty seconds after air injection. In contrast, vagotomized animals exhibited a significant RNA increase (147 +/- 11% of the control) in response to a decrease in SBP (from 93 +/- 6 to 78 +/- 5 mmHg) and an increase in CVP ten seconds after the administration of air. In SAD group, a rapid and remarkable decline in SBP (from 85 +/- 13 to 47 +/- 12 mmHg) occurred ten seconds after the injection of air. Despite this hypotension, RNA decreased nearly to a noise level after administration of air.(ABSTRACT TRUNCATED AT 250 WORDS)