The effect of low-dose ketamine on fentanyl-induced respiratory depression

This study evaluated if adding low-dose ketamine to fentanyl could offer a haemodynamically stable drug combination with little respiratory side-effects. Eight healthy, consenting male volunteers received in a random, cross-over and double-blind fashion both fentanyl 2 μgkg⁻¹ + ketamine 0.25 mgkg⁻¹ and fentanyl 2 μgkg⁻¹ + placebo. The fentanyl and placebo reduced minute ventilation, alveolar ventilation and oxygen consumption ( p < 0.05), with little effect on haemodynamics. After fentanyl and ketamine, the decrease in minute ventilation and alveolar ventilation was attenuated compared to the placebo-containing combination ( p < 0.05), but with a simultaneous increase in oxygen consumption ( p < 0.05) and stimulation of haemodynamics ( p < 0.05). Both treatments decreased oxygen saturation and arterial oxygen pressure similarly. Ketamine thus attenuated the fentanyl-induced reduction in ventilation without preventing the decrease in blood oxygenation. In conclusion, combining low-dose ketamine to fentanyl offers no benefits in terms of preventing respiratory depression.     

丙泊酚镇静下氟马西尼对脑电双频指数的影响

目的 研究丙泊酚镇静时氟马西尼对患者脑电双频指数(BIS)的影响.方法 择期行妇科子宫肌瘤剥出术或全子宫切除术患者40例,ASA Ⅰ或Ⅱ级,随机均分为两组.实施椎管内麻醉,术中采用丙泊酚镇静,维持患者BIS值在65±3.分别在关腹时静注氟马西尼0.01 mg/kg(F组)和生理盐水0.1 ml/kg(C组).观察给药前、给药后2、4、6、8、10、15、20 min时的BIS值.结果 给药后6～20 min F组BIS值显著高于C组(P<0.05).结论 丙泊酚镇静时氟马西尼可提高患者的BIS值,加快患者苏醒.     

Speed of reversal of midazolam-induced respiratory depression by flumazenil - a study in patients undergoing upper G.I. endoscopy

Intravenous midazolam was given to 17 patients coming to upper G.I. endoscopy. All patients had an ear oximeter and calibrated induction plethysmograph attached to record oxygen saturation and minute volume continuously. Midazolam induced significant depression of respiration. Following removal of the endoscope, a new base line was obtained before giving intravenous flumazenil in an attempt to reverse the sedative and ventilatory effects of midazolam. When 0.5 mg of flumazenil was given over 20 s, followed by 0.1 mg every minute, up to a total of 1.0 mg, all patients were apparently awake in under 2 min. Although the flumazenil had clearly reversed the sedative effects of midazolam, the ventilatory effects were largely uninfluenced. The implications are discussed.     

The effect of flumazenil on the recovery time of dental patients sedated with diazepam

Flumazenil is an imidazobenzodiazepine that binds specifically to the central benzodiazepine receptor and antagonizes the actions of diazepam and other benzodiazepines. Previous studies in Europe have shown flumazenil at doses of 2 to 30 mg IV to reverse sedation in patients sedated with flunitrazepam, midazolam, and diazepam when evaluated by subjective criteria. The purpose of this study was to determine if flumazenil at 0.015 mg/kg IV was efficacious in shortening the recovery time of young, healthy dental patients sedated with diazepam (0.15 mg/kg IV) and restoring their psychomotor function to presedation levels. A total of 21 patients were randomized to placebo or flumazenil, sedated with diazepam, underwent a restorative dental procedure, and were then administered the test drug. Evaluations of psychomotor function by the Trieger test, Digit-Symbol Substitution test, Romberg test, and nurse questioning were carried out before sedation and at 10-minute intervals after test drug. Observations by the patients and nurses were not significantly different before versus after test drug. The investigator, however, found that flumazenil resulted in more rapid awakening. Patients treated with placebo exhibited significantly greater deficits in the number of dots missed and sum of deviations on the Trieger test than flumazenil-treated patients. Similar time-related deficits were recorded for the Digit-Symbol Substitution test. Flumazenil, at a dose of 0.015 mg/kg, was found to be efficacious in reducing the recovery time after diazepam sedation in dental patients.     

Clinical investigation of flumazenil in reversing the respiratory effects of diazepam

Eight patients (ASA I-II) scheduled for a minor surgery under lumbar epidural or spinal anesthesia were studied. The patients were sedated with approximately 0.2 mg.kg-1 of bolus injection followed by 0.2 mg.kg-1.min-1 of continuous infusion of diazepam. In order to evaluate the reversing effects of 0.2 mg of flumazenil on the respiratory effects of diazepam, the following parameters were examined at three points, namely 1) control period, 2) during infusion of diazepam, and 3) ten minutes following injection of flumazenil; tidal volume, respiratory frequency, minute volume, inspiratory time/total time of breath (Tl/Tt) and %RC with a respiratory inductive plethysmograph, ventilatory response to carbon dioxide using a modified Read's rebreathing method. We found that with flumazenil, tidal volume and the slope of the ventilatory response curve to carbon dioxide increased and arterial carbon dioxide tension decreased. However, minute volume, respiratory frequency, Tl/Tt and %RC were unchanged with flumazenil. Flumazenil did not change other clinical features and did not produce any abnormal data in laboratory examination. We conclude that flumazenil reverses the respiratory effects of diazepam at least for ten minutes following its injection without producing any complications and side effects.     

Lack of effect of flumazenil on the reversal of propofol anaesthesia

Propofol, like the benzodiazepines, activates the GABA_A receptor-chloride ionophore complex; they potentiate one another. Since neither pharmacodynamic nor pharmacokinetic data concerning drug interaction between flumazenil and propofol is available, and especially considering the relationship of binding sites, flumazenil, the antagonist of benzodiazepines, was investigated to determine its effect upon recovery from propofol anaesthesia. Forty women receiving dilatation and curettage procedures were included in this double-blind test. After 50 μg fentanyl, propofol 2 mg · kg^-1 was injected for induction and followed by infusion at the rate of 15 mg · kg^-1 · hr^-1. After the operation, patients were given normal saline (Group A) or flumazenil 10 μg · kg^-1 (Group B) randomly.
Recovery time in Group A was 15.2±5.1 min and Group B 15.8±4.8 min. Propofol concentrations at the end of infusion were 4.17±1.33 μg ·ml^-1 (Group A) and 4.03±1.45 μg · ml^-1 (Group B); these then declined to 1.22±0.17 μg · ml^-1 (Group A) and 1.18±0.15 μg · ml^-1 (Group B) when patients were able to open their eyes on command. No significant differences were found between the groups based on propofol concentrations and recovery time, nor did haemodynamic changes differ between them after administration of reversal agents. It was concluded that flumazenil 10 μg · ml^-1 does not influence recovery from propofol anaesthesia.     

The effect of the benzodiazepine antagonist flumazenil on regional cerebral blood flow in human volunteers

The influence of the benzodiazepine antagonist flumazenil on regional cerebral blood flow (rCBF) was investigated in ten healthy, alert volunteers. The design was a randomized, placebo-controlled, double-blind, cross-over study. rCBF was measured by 133-Xe inhalation and single photon emission computerized tomography, SPECT, immediately before, and 5 and 35 min after intravenous injection of flumazenil 1.0 mg or placebo. In addition, mean arterial blood pressures or PaCO2, rCBF were analysed for changes in various regions of interest (RoI). No alterations were found either in the global CBF or in rCBF in RoI after flumazenil injection. The results showed that a clinically active dose of flumazenil did not directly affect the cerebral circulation in the normal brain and indicated absence of significant intrinsic activity of the drug.     

The effect of midazolam on the memory during cesarean section and the modulation by flumazenil

In 30 patients (ASA-1) for elective Cesarean section who had given informed consent, characteristics of amnesia induced by midazolam (M) and their modulation by flumazenil (F) were examined. Spinal anesthesia was performed with dibucaine. After the delivery, the baby was shown to the mother. Then 21 patients were given bolus intravenous injection of M until the patient got into sleep and the inhalation of nitrous oxide mixed with oxygen was started. At the end of surgery bolus injection of F 0.1 mg was cumulatively repeated until the patient awoke. Nine patients were given only nitrous oxide and oxygen inhalation after the delivery. The remembrance of the baby face and the doses of M and F were compared. In group given M, 14 patients recalled their baby's face whereas 7 did not. The average doses of M and F in patients with memory were 69 micrograms.kg-1 and 2.5 micrograms.kg-1, respectively, whereas the average dose of M and F in patients without memory were 94 micrograms.kg-1 and 4.2 micrograms.kg-1, respectively. In the patients without M injection, all could recall the face of the baby. These results suggest that M could produce retrograde amnesia, when combined with nitrous oxide inhalation, which is not reversed by F.     

The respiratory effects of reversing midazolarn sedation with flumazenil in the presence or absence of narcotics

The purpose of this study was to determine the effects of reversal of sedation with flumazenil (F), in the presence or absence of opiates, on arterial oxygen saturation (Sao₂) and cnd-tidal CO₂ (E_Tco₂). Twenty-four patients undergoing surgery and epidural anaesthesia were studied. Twelve patients (Group A) were orally premedicated with diazepam and 0.1 mg·kg^-1 morphine i.m. Intraoperative sedation consisted of midazolam 0.1 mg·kg^-1 and pethidine 0.7 mg·kg^-1 i.v. Twelve patients (Group B) were premedicated with diazepam and sedated intraoperatively with 0.1 mg·kg^-1 midazolam. In the recovery room, six patients in each group were randomly allocated to receive 1 mg of flumazenil while the others were allowed to awaken spontaneously (control). Sedation (eyes open vs closed), Sao₂, E_Tco₂, respiratory rate, blood pressure and pulse were non-invasively monitored for 90 min. Administration of flumazenil resulted in a statistically significant increase in the number of patients with eyes open in both groups at 5 min, lasting 15 min in Group A and 30 min in Group B patients. An increase in Sao₂ from 15–45 min after injection of flumazenil was observed only in Group B. No significant difference between groups in any other parameter was found. We concluded that reversal of benzodiazepine (BZ) sedation with flumazenil improved Sao₂ in patients sedated with only BZ; in the presence of BZ and opiates, flumazenil did not affect respiratory parameters.     

The effect of benzodiazepine receptor antagonism by flumazenil on the MAC of halothane in the rat

The effects of a benzodiazepine receptor agonist and an antagonist on the MAC of halothane required to achieve anesthesia were evaluated to explore the possible functional interaction between halothane and the benzodiazepine receptor. Rats were anesthetized with halothane and then administered midazolam (a benzodiazepine agonist) and/or flumazenil (a benzodiazepine antagonist). Flumazenil in doses of 0.1 mg/kg and 1.0 mg/kg was found to have no effect on the MAC of halothane. Midazolam (1.0 mg/kg) lowered the MAC of halothane by 37%. This decrease in MAC was inhibited by coadministration of flumazenil. The absence of an increase in the MAC of halothane in the presence of flumazenil suggests that halothane does not interact with the benzodiazepine receptor, directly or indirectly, to produce its anesthetic action.     

抑郁障碍对腹膜透析患者的影响

目的：研究腹膜透析（腹透）患者产生抑郁障碍的可能因素及其对腹透的影响,尝试药物治疗,以期改善生活质量,方法：选择无精神病史的规律性腹透患者43例,进行汉密顿抑郁量表（HAMD）和抑郁自评量表（SDS）评分,并分为抑郁组和非抑郁组,在组间进行性别,年龄,文化程度和医疗付费情况的比较,观察患者透析充分性,营养,感染率,主不业率及顺应性在组织间的差异,并选择重度抑郁状态者预以抗抑郁治疗（Prozac20mg/d),观察疗效,结果：（1）37．2％的患者存在抑郁障碍,（2）通过比较,两组的年龄,性别,文化,程度,婚烟障碍和医疗付费情况均无显著差异,（3）两组间的顺应性差异有显著性意义（不顺应者在抑郁组中占53．3％,非抑郁组仅7．7％,P＜0．01）,感染率差异也有显著性意义（抑郁组：0．04）,SAG评分示抑郁组营养不良占62％,非抑郁组占4．3％,（P＜0．05）,（4）在16例中选6例预Prozac治疗1月后重测HAMD和SDS评分,相关因子分下降（例少未统计）,结论：抑郁状态在腹透患者中常见,它可造成腹透患者的营养不良,顺应性下降,透析不充分,感染率上升,抗抑郁的药物治疗可望改善患者的抑郁状态。