Potencies of doxapram and hypoxia in stimulating carotid-body chemoreceptors and ventilation in anesthetized cats.
The effects of doxapram on carotid chemoreceptor activity and on ventilation (phrenic-nerve activity) were tested before and after denervation of the peripheral chemoreceptors in cats. Doxapram was found to be a potent stimulus to the carotid chemoreceptors; the stimulation produced by 1.0 mg/kg doxapram, iv, equalled that produced by a Pao2 of 38 torr. Doxapram also increased phrenic-nerve activity in doses as low as 0.2 mg/kg, iv. After denervation of the peripheral chemoreceptors, doxapram in doses as large as 6 mg/kg failed to stimulate ventilation. It is concluded that (in anesthetized cats) doxapram in doses of less than 6 mg/kg increases ventilation by direct stimulation of the carotid, and, probably, the aortic, chemoreceptors, not by a direct effect on the medullary respiratory center. (+info)
Effects of anesthetics on ponto-geniculo-occipital waves from the oculomotor nucleus of the cat.
Effects of anesthetics and doxapram on pontogeniculo-occipital (PGO) waves from the oculomotor nucleus were studied in acute experiments in cats paralyzed by gallamine triethiodide. The anesthetic agents studied in the present experiment (thiopental, ketamine, Innovar, nitrous oxide, and halothane) decreased, while doxapram increased, the total number of PGO waves. As the doses of anesthetics increased, PGO waves were abolished, but they returned to control levels or below control levels when the concentrations of anesthetics were decreased. The results indicate that the anesthetics studied inhibit the activity of the central mechanism associated with the oculomotor system. PGO waves may prove a useful index of the level of anesthesia. (+info)
Ultrasound measurements of fetal breathing movements in the rat.
The goal of this study was to determine when fetal breathing movements (FBMs) commence in the rat and to characterize age-dependent changes of FBMs in utero. These data provide a frame of reference for parallel in vitro studies of the cellular, synaptic, and network properties of the perinatal rat respiratory system. Ultrasound recordings were made from unanesthetized Sprague-Dawley rats from embryonic (E) day 15 (E15) to E20. Furthermore, the effects of respiratory stimulants (doxapram and aminophylline) and hypoxia on FBMs were studied. Single FBMs, occurring at a very low frequency (approximately 8 FBMs/h), commenced at E16. The incidence of single FBMs increased to approximately 80 FBMs/h by E20. Episodes of clustered rhythmic FBMs were first observed at E18 (approximately 40 FBMs/h). The incidence of episodic clustered FBMs increased to approximately 300 FMBs/h by E20, with the duration of each episode ranging from approximately 40 to 180 s. Doxapram, presumably acting to stimulate carotid body receptors, did not increase FBMs until E20, when the incidence of episodic clustered FBMs increased twofold. Aminophylline, a central-acting stimulant, caused an increase in episodic clustered FBMs after E17, reaching significance at E20 (3-fold increase). Exposing the dam to 10% O(2) caused a rapid, marked suppression of FBMs (5-fold decrease) that was readily reversed on exposure to room air. (+info)
Acute hypercapnic respiratory failure in patients with chronic obstructive lung disease: risk factors and use of guidelines for management.
BACKGROUND: On the basis of a retrospective survey by this unit it was suggested that patients with acute ventilatory failure should be given sufficient controlled oxygen treatment to raise the arterial oxygen tension (PaO2) to above 6.6 kPa, with the addition of a respiratory stimulant if the hydrogen ion concentration ([H+]) rose above 55 nmol/l and assisted ventilation if the patient remained acidotic despite these measures. This study was designed to verify the prognostic factors that determine survival in acute ventilatory failure and determine the outcome when our guidelines were implemented. METHODS: One hundred and thirty nine episodes of acute hypercapnic (type II) respiratory failure were studied prospectively in 95 patients admitted with acute exacerbations of chronic obstructive lung disease. Patients had to have a PaO2 below 6.6 kPa and an arterial carbon dioxide tension (PaCO2) above 6.6 kPa while breathing air. RESULTS: The mortality associated with episodes of acute ventilatory failure was 12%. Patients who died tended to be older and were significantly more acidotic, hypotensive, and uraemic on admission than those who survived, but they had similar degrees of hypoxaemia and hypercapnia. Death occurred in 10 of the 39 episodes in which arterial [H+] rose to 55 nmol/l or above, compared with seven of the 100 episodes in which it remained below 55 nmol/l. The respiratory stimulant doxapram was used in 37 episodes and was associated with a reduction in [H+] below 55 nmol/l within 24 hours in 23 episodes. Assisted ventilation was used in only four episodes. CONCLUSION: Arterial [H+] is an important prognostic factor for survival. Most patients treated according to the guidelines outlined above can be managed successfully without assisted ventilation. (+info)
High dose caffeine citrate for extubation of preterm infants: a randomised controlled trial.
OBJECTIVE: To compare two dosing regimens for caffeine citrate in the periextubation period for neonates born at less than 30 weeks gestation in terms of successful extubation and adverse effects. DESIGN: A multicentre, randomised, double blind, clinical trial. SETTING: Four tertiary neonatal units within Australia. PATIENTS: Infants born less than 30 weeks gestation ventilated for more than 48 hours. INTERVENTIONS: Two dosing regimens of caffeine citrate (20 v 5 mg/kg/day) for periextubation management. Treatment started 24 hours before a planned extubation or within six hours of an unplanned extubation. MAIN OUTCOME MEASURE: Failure to extubate within 48 hours of caffeine loading or reintubation and ventilation or doxapram within seven days of caffeine loading. RESULTS: A total of 234 neonates were enrolled. A significant reduction in failure to extubate was shown for the 20 mg/kg/day dosing group (15.0% v 29.8%; relative risk 0.51; 95% confidence interval (CI) 0.31 to 0.85; number needed to treat 7 (95% CI 4 to 24)). A significant difference in duration of mechanical ventilation was shown for infants of less than 28 weeks gestation receiving the high dose of caffeine (mean (SD) days 14.4 (11.1) v 22.1 (17.1); p = 0.01). No difference in adverse effects was detected in terms of mortality, major neonatal morbidity, death, or severe disability or general quotient at 12 months. CONCLUSIONS: This trial shows short term benefits for a 20 mg/kg/day dosing regimen of caffeine citrate for neonates born at less than 30 weeks gestation in the periextubation period, without evidence of harm in the first year of life. (+info)
Ovalbumin sensitization alters the ventilatory responses to chemical challenges in guinea pigs.
Patients with chronic bronchial asthma show a depressed ventilatory response to hypoxia (DVH), but the underlying mechanism remains unclear. We tested whether DVH existed in ovalbumin (Ova)-treated guinea pigs, an established animal model of asthma. Twelve guinea pigs were exposed to Ova (1% in saline) or saline aerosol (control) for 5 min, 5 days/wk, for 2 wk. After completing aerosol exposure, the animals were anesthetized and exposed to systemic hypoxia. Ova treatment had no effects on animal body weight, baseline cardiorespiratory variables, or arterial blood O2 and CO2 tensions, but it attenuated the ventilatory response to hypoxia (10 breaths of pure N2) by 65% (P < 0.05). When the animals were subjected to intracarotid injections of sodium cyanide (20 microg) and doxapram (2 mg) to selectively stimulate carotid chemoreceptors, the ventilatory responses were reduced by 50% (P < 0.05) and 74% (P < 0.05), respectively. In contrast, Ova exposure failed to affect the ventilatory response to CO2 (7% CO2-21% O2-balance N2 for 5 min; P > 0.05). Furthermore, the apneic response evoked by stimulating bronchopulmonary C fibers (PCFs) with right atrial injection of capsaicin (5 microg) was markedly increased in the Ova-sensitized group (5.02 +/- 1.56 s), compared with the control group (1.82 +/- 0.45 s; P < 0.05). These results suggest that Ova sensitization induces a DVH in guinea pigs, which probably results from an attenuation of the carotid chemoreceptor-mediated ventilatory excitation and an enhancement of the PCF-mediated ventilatory inhibition. (+info)
Doxapram only slightly reduces the shivering threshold in healthy volunteers.
We determined the effects of doxapram on the major autonomic thermoregulatory responses in humans. Nine healthy volunteers were studied on 2 days: control and doxapram (IV infusion to a plasma concentration of 2.4 +/- 0.8, 2.5 +/- 0.9, and 2.6 +/- 1.1 microg/mL at the sweating, vasoconstriction, and shivering thresholds, respectively). Each day, skin and core temperatures were increased to provoke sweating, then reduced to elicit peripheral vasoconstriction and shivering. We determined the sweating, vasoconstriction, and shivering thresholds with compensation for changes in skin temperature. Data were analyzed with paired t-tests and presented as mean +/- sd; P < 0.05 was considered statistically significant. Doxapram did not change the sweating (control: 37.5 degrees +/- 0.4 degrees C, doxapram: 37.3 degrees +/- 0.4 degrees C; P = 0.290) or the vasoconstriction threshold (36.8 degrees +/- 0.7 degrees C versus 36.4 degrees +/- 0.5 degrees C; P = 0.110). However, it significantly reduced the shivering threshold from 36.2 degrees +/- 0.5 degrees C to 35.7 degrees +/- 0.7 degrees C (P = 0.012). No sedation or symptoms of panic were observed on either study day. The observed reduction in the shivering threshold explains the drug's efficacy for treatment of postoperative shivering; however, a reduction of only 0.5 degrees C is unlikely to markedly facilitate induction of therapeutic hypothermia as a sole drug. (+info)
The effect of doxapram on brain imaging in patients with panic disorder.
Administration of doxapram hydrochloride, a respiratory stimulant, is experienced by panic disorder patients to be similar to panic attacks but has reduced emotional effect in normal volunteers, thus providing a laboratory model of panic for functional imaging. Six panic patients and seven normal control subjects underwent positron emission tomography with (18)F-deoxyglucose imaging after a single-blinded administration of either doxapram or a placebo saline solution. Saline and doxapram were administered on separate days in counterbalanced order. Patients showed a greater heart rate increase on doxapram relative to saline than controls, indicating differential response. On the saline placebo day, patients had greater prefrontal relative activity than controls. In response to doxapram, patients tended to decrease prefrontal activity more than controls, and increased cingulate gyrus and amygdala activity more than controls. This suggests that panic disorder patients activate frontal inhibitory centers less than controls, a tendency that may lower the threshold for panic. (+info)