Little is known about the performance of ultrasonic nebulizers during different ventilation patterns when these nebulizers are used to deliver drugs to intubated, ventilated patients. A method that enables the performance of an ultrasonic nebulizer to be evaluated is described. We used an in vitro model to examine the performance of the DeVilbiss Ultra-Neb 2000 ultrasonic nebulizer under positive pressure ventilation. Performance was measured at different rates of nebulization and under changing conditions of positive end-expiratory pressure (PEEP), inspiratory flow rate, inspiratory time and minute volume. The volume of saline nebulized was unchanged by variations in positive end expiratory pressure from 0 to 5 cm to 10 cm H2O, in minute ventilation and in inspiratory flow rate. An increase in the inspiratory time resulted in an increase in the volume of saline nebulized and this volume was greater as the power setting of the nebulizer was increased. We conclude that ultrasonic nebulizers may be affected by different patterns of ventilation and that this simple in vitro assessment of nebulizer function in an intensive care setting may be of value prior to nebulizer use.

BACKGROUND:Heart rate (HR) or mean arterial blood pressure (MAP) may increase in response to incision despite the absence of a motor response. The authors hypothesized that the MAC-BAR (minimum alveolar concentration of an anesthetic that blocks adrenergic response to incision) for isoflurane would exceed that for desflurane, and that fentanyl would decrease the MAC-BAR for each anesthetic in a dose-dependent manner. METHODS:Seventy-one patients were randomly allocated to one of six groups: desflurane or isoflurane without fentanyl or with 1.5 or 3 microg/kg fentanyl given intravenously 5 min before surgical incision. Anesthesia was induced with 2 mg/kg propofol given intravenously, and tracheal intubation facilitated with 0.1 mg/kg given intravenously. The first patient in each group received 1 MAC (end-tidal) of the inhaled anesthetic in 60% nitrous oxide (0.55 MAC), balance oxygen, maintained for at least 10 min before incision. The response was considered positive if the HR or MAP increased 15% or more. If the response was positive, the end-tidal concentration given to the next patient was 0.3 MAC greater; if the response was negative, the end-tidal concentration was 0.3 MAC less. The MAC-BAR level was calculated as the mean of four independent cross-over responses in each group. RESULTS:Desflurane and isoflurane anesthesia with 60% nitrous oxide did not change HR (P > 0.05) and decreased MAP (P < 0.05) before incision. Plasma epinephrine and norepinephrine concentrations after anesthesia and before incision were normal in all groups. The MAC-BAR level, without fentanyl, did not differ (P > 0.05) between desflurane (1.30 +/- 0.34 MAC [mean +/- SD]) and isoflurane (1.30 +/- 0.18 MAC). Fentanyl given at 1.5 microg/kg intravenously equivalently (P > 0.05) reduced the MAC-BAR for desflurane (to 0.40 +/- 0.18 MAC; P < 0.05) and isoflurane (to 0.55 +/- 0.00 MAC; P < 0.05), but a further increase in fentanyl to 3 microg/kg caused no greater decrease in the MAC-BAR for desflurane (0.48 +/- 0.16 MAC) and isoflurane (0.40 +/- 0.30 MAC). CONCLUSIONS:Clinically attainable doses of desflurane and isoflurane, in 60% nitrous oxide (0.55 MAC), block the cardiovascular response to surgical incision at 1.3 MAC. Fentanyl given at 1.5 microg/kg decreases the MAC-BAR for each agent with no further decrease produced by 3 microg/kg fentanyl.

BACKGROUND:Pupil size is determined by an interaction between the sympathetic and parasympathetic divisions of the autonomic nervous system. Noxious stimulation dilates the pupil in both unanesthetized and anesthetized humans. In the absence of anesthesia, dilation is primarily mediated by the sympathetic nervous system. In contrast, pupillary dilation in cats given barbiturate or cloralose anesthesia is mediated solely by inhibition of the midbrain parasympathetic nucleus. The mechanism by which noxious stimuli dilate pupils during anesthesia in humans remains unknown. Accordingly, the authors tested the hypothesis that the pupillary dilation in response to noxious stimulation during desflurane anesthesia is primarily a parasympathetic reflex.METHODS:In six volunteers, the alpha-I adrenergic receptors of the iris musculature were blocked by unilateral administration of topical dapiprazole; six other volunteers were given unilateral topical tropicamide to block the muscarinic receptors in the iris. Desflurane anesthesia was subsequently induced in all volunteers. Sympathetic nervous system activation, with reflex dilation of the pupil, was produced by noxious electrical stimulation during 4% and 8% end-tidal desflurane, and by a rapid 4%-to-8% step-up in the desflurane concentration. Pupil diameter and the change in pupil size induced by a light stimulus (light reflex amplitude) were measured with infrared pupillometry.RESULTS:Dapiprazole drops produced a Horner's miosis, but pupils were equally small after induction of anesthesia. Pupillary dilation after noxious stimulation and desflurane step-up was identical in the unblocked and dapiprazole-blocked pupils. After tropicamide administration, the pupil was dilated and the light reflex was completely inhibited. Noxious stimulation nonetheless produced a slight additional dilation.CONCLUSIONS:During desflurane anesthesia, pupillary dilation in response to noxious stimulation or desflurane step-up is not mediated by the sympathetic nervous system (as it is in unanesthetized persons). Although inhibition of the pupillo-constrictor nucleus may be the cause of this dilation, the mechanism remains unknown.

Initial, but not subsequent, inhalation of 8% desflurane produces transient sympathetic stimulation.We hypothesized that initial but not subsequent increases should produce pupil dilation, and that N2 O, fentanyl, and clonidine, but not esmolol, should blunt the response. In 10 volunteers, we maintained anesthesia with 4% end-tidal desflurane in oxygen for 32 min, then increased the concentration to 8% for 10 min. In nine of the volunteers, we twice repeated the increase to 8%, separating each increase by a 32-min period at 4%. On separate days, five volunteers received 4%-8% desflurane in 60% N2 O; five received fentanyl 1.5 micro gram/kg or 4.5 micro gram/kg intravenously 5 min before 4%-8% desflurane; four received clonidine 4.3 micro gram/kg, orally, 90 min before 4% to 8%; and four received esmolol 0.75 mg/kg, intravenously, 1.5 min before 4%-8%. Without other drugs present, 4%-8% desflurane transiently increased pupil diameter to 5.4 +/- 0.5 mm (mean +/- SD), with subsequent 4%-8% increases producing attenuated responses (2.9 +/- 1.5 and 3.2 +/- 1.8 mm). N2 O produced a higher peak (6.2 +/- 0.7 mm). Fentanyl 1.5 micro gram/kg and 4.5 micro gram/kg decreased peak diameter (2.3 +/- 0.9 and 1.6 +/- 0.3 mm), as did clonidine (2.3 +/- 1.7 mm) but not esmolol. We conclude that, concurrent with sympathetic stimulation, an initial rapid increase in desflurane concentration transiently increases pupil diameter, whereas repeated increases produce attenuated responses. N2 O augments, fentanyl and clonidine attenuate, and esmolol does not affect the response. (Anesth Analg 1995;81:372-8)

Background: It was hypothesized that stimulation of rapidly adapting airway receptors produces the transient (2-4 min) circulatory responses to rapid increases in desflurane concentrations greater than 6%. Accordingly, it was reasoned that increasing the concentration of desflurane in one lung, without altering the concentration of desflurane in systemic blood, should cause cardiovascular stimulation, whereas once the airway receptors had adapted to the stimulation, an initial increase in the systemic concentration of desflurane should have little effect.Methods: After placement of a double-lumen endotracheal tube in four volunteers and establishment of a steady-state level of 4% desflurane in both lungs, the desflurane concentration was rapidly increased from 4% to 8% in one lung while decreasing It in the other, thereby obviating any increase in the systemic desflurane blood concentration (confirmed by analysis). After returning the desflurane end-tidal concentration to 4% in both lungs, this process was repeated for the contralateral lung thereby having exposed both lungs to 8% desflurane without increasing the systemic desflurane concentration, After returning desflurane concentration to 4%, it was increased in both lungs simultaneously to 8% and consequently in blood to 8% of an atm.Results: Rapid increases in desflurane concentrations in either lung, but not blood, significantly increased heart rate (17 +/- 5 beats/min, mean +/- SE, Pt 0.05) and mean arterial blood pressure (15 +/- 5 mmHg, P < 0.05), but a greater increase in heart rate (43 +/- 5 beats/min, P < 0.05) and mean arterial blood pressure (46 +/- 11 mmHg, P < 0.05) occurred when both lungs were exposed simultaneously to rapidly increased desflurane concentration for the second time within 90 min. This result did not differ from the increase occurring on another day when both lungs and blood were exposed for the first time that day to 8% desflurane (heart rate 40 +/- 7 beats/min, P = 0.8; mean arterial blood pressure 40 +/- 3 mmHg, P = 0.5).Conclusions: It was concluded that at least two sites respond to a rapid increase in desflurane concentrations greater than 6%: one site in the airways and/or lungs, and at least one other in a highly perfused tissue(s), The systemic site contributes more importantly.

Background A rapid increase in desflurane concentration to greater than 1 MAC transiently increases heart rate, arterial blood pressure, and circulating catecholamine concentration. Because propofol decreases sympathetic outflow, it was hypothesized that propofol would blunt these responses. Methods To test this hypothesis, five healthy male volunteers were studied three times. After induction of anesthesia with 2 mg.kg-1 propofol, anesthesia was maintained with 4% end-tidal desflurane in oxygen (0.55 MAC) via an endotracheal tube for 32 min. On separate occasions, in random order, either no propofol or 2 mg.kg-1 propofol was administered either 2 or 5 min before increasing end-tidal desflurane concentration from 4% to 8%. Results Without propofol pretreatment, the increase to 8% desflurane transiently increased heart rate (from 63 +/- 3 beats/min to 108 +/- 5 beats/min, mean +/- SEM; P < 0.01), mean arterial pressure (from 73 +/- 1 mmHg to 118 +/- 6 mmHg; P < 0.01), and epinephrine concentration (from 14 +/- 1 pg.ml-1 to 279 +/- 51 pg.ml-1; P < 0.05). There was no significant change in norepinephrine concentration (from 198 +/- 37 pg.ml-1 to 277 +/- 46 pg.ml-1). The peak plasma epinephrine concentration was attenuated by each propofol pretreatment (158 +/- 35 pg.ml-1, propofol given 2 min before, and 146 + 41 pg.ml-1, propofol given 5 min before; P < 0.05), but neither propofol pretreatment modified the cardiovascular or norepinephrine responses. Conclusions Although able to blunt the increase in epinephrine concentration, propofol 2 mg.kg-1 propofol does no attenuate the transient cardiovascular response to a rapid increase in desflurane concentration to greater than 1 MAC.

Background: Rapid increases in desflurane concentrations above minimum alveolar concentration (MAC) can cause transient (2-4-min) circulatory changes, possibly from stimulation of rapidly-adapting airway receptors. We hypothesized that the initial increase in concentration would produce greater changes than subsequent increases.Methods: Anesthesia was induced with propofol in nine volunteers (25 +/- 1 yr old, mean +/- SE) and maintained with 4% end-tidal desflurane for 32 min. We increased the desflurane to 8% (1.1 MAC) in 1 min, maintained this concentration for 10 min, and then decreased it to 4% for 32 min. We repeated this process twice. After 1 week, 5 subjects were treated similarly except that the second increase in concentration occurred 10 min and (on a separate occasion) 75 min after the initial increase. Four subjects received the initial increase after 75 rather than 32 min of anesthesia. In four we applied the repeated sequences in a background of 60% nitrous oxide. When a minimal cardiovascular response followed an increase of anesthetic concentration, a 60-s supramaximal 100-Hz tetanic stimulus was applied to an ulnar nerve percutaneously to test for sympathetic responsiveness.Results: The initial increase in concentration increased heart rate (HR) from 57 +/- 2 to a peak of 119 +/- 7 beats/min (P < 0.05); mean arterial blood pressure (MAP) from 66 +/- 3 to 119 +/- 5 mmHg (P < 0.05); and plasma epinephrine by > 10-fold (P < 0.05). The second and third increases in desflurane concentration increased HR and MAP by less than 20% of the initial increases, regardless of the timing of the later concentration increases. Responses to initial concentration increases after 75 min of anesthesia did not differ from those after 32 min. Increases in plasma epinephrine with the second and third increases in desflurane concentration were attenuated. Subjects who did not responded to the second or third increase in desflurane always responded to tetanic electrical stimulation with substantial increases in HR and MAP (P < 0.05). Addition of nitrous oxide did not change results except for a smaller increase in MAP (P < 0.05). Ulnar nerve stimulation increased HR and MAP but not epinephrine or norepinephrine concentrations.Conclusions: An initial rapid increase in desflurane to 1.1 MAC produces much more stimulation than do subsequent increases, regardless of the presence of nitrous oxide. The decreased response is consistent with the hypothesis that stimulation of rapidly-adapting airway receptors produce the initial response.