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Biomedical subjects

A Tung

Publications and source records attributed to A Tung.

16 recordsLinked to original sources
PubMed2001

Sleep inducing effects of propofol microinjection into the medial preoptic area are blocked by flumazenil.

The intravenous anesthetic, propofol, has been shown to increase sleep when microinjected into the medial preoptic area (MPA) of the rat. Similar increases in sleep have also been observed with triazolam, pentobarbital and ethanol microinjection. Together, these findings implicate the MPA as an important anatomic site mediating the effects of sedatives on naturally occurring sleep. Although the molecular mechanism by which propofol in the MPA acts to induce sleep is unclear, potentiating effects on the GABA(A) receptor complex may play a role. To assess this possibility, we microinjected propofol alone, and in combination with the benzodiazepine receptor antagonist flumazenil, into the MPA. At a dose of 0.76 microg, flumazenil had no effect on sleep when given alone, and completely blocked the increase in sleep caused by a 40-ng dose of propofol although it did not affect the increase in sleep caused by an 80-ng dose of propofol. These data suggest that the sleep inducing property of propofol is in part mediated by direct or indirect actions on the GABA(A)-benzodiazepine receptor complex.

Anesthetics, Intravenous↗
PubMed2001

The hypnotic effect of propofol in the medial preoptic area of the rat.

Recent introduction of the intravenous anesthetic propofol as an ICU sedative has allowed a deeply sedated state to be maintained for extended periods in the ICU without delays in emergence. Although such sedation has been advocated to promote physiologic sleep, little evidence exists to support such a strategy. To explore propofol's effect on sleep regulation, we administered propofol directly into the medial preoptic area (MPA) of the rat, an anatomic site where administration of other sedatives (triazolam and phenobarbital) also induce sleep. We performed three two-hour sleep studies in the daytime with the lights on following the administration of propofol (8 ng or 40 ng) or vehicle (intralipid). The higher dose of propofol significantly reduced sleep latency and increased nonREM and total sleep times when compared to vehicle. REM sleep times, intermittent waking times and number of transitions were not altered. Mean nonREM sleep bout length was increased significantly at the higher dose. These findings suggest that propofol may enhance sleep by acting at a hypothalamic site.

Animals↗
PubMed2001

The relationship of sedation to deliberate self-extubation.

STUDY OBJECTIVES: To evaluate the relationship between sedative therapy and self-extubation in a large medical-surgical intensive care unit (ICU). DESIGN: Retrospective, case-controlled study. SETTING: Large teaching hospital. PATIENTS: All adult patients who underwent unplanned self-extubation during a 12-month period (n = 50). Each patient was matched to two control patients who did not self-extubate based on age, gender, dates in hospital and diagnosis. INTERVENTIONS: none. MEASUREMENTS: Data collected included time to self extubation, dosages and types of benzodiazepines, opioid analgesics, antipsychotics, and hypnotics. Data on the degree of agitation as assessed by nursing staff also were obtained. MAIN RESULTS: When compared to controls, patients in the self-extubation group were more likely to have received benzodiazepines (59% vs. 35%; p < 0.05), but equally likely to have received opioids and/or paralytic drugs. Patients who self-extubated were twice as likely as controls to be agitated (54% vs. 22%; p < 0.05). Use of benzodiazepines was more common in agitated patients than in nonagitated patients (62% vs. 35%; p < 0.02). Among nonagitated patients who self-extubated, increased use of benzodiazepines (57% vs. 29%; p < 0.05) was noted when compared to nonagitated controls. CONCLUSIONS: In intubated ICU patients, benzodiazepines may not consistently treat agitation effectively or prevent self-extubation. Such an effect may be due to paradoxical excitation, disorientation during long-term administration, or differences in drug administration between ICU and operating room (OR) environments.

Aged↗
PubMed2001

Prolonged sedation with propofol in the rat does not result in sleep deprivation.

UNLABELLED: The use of propofol provides sedation without prolonging emergence in patients in the Intensive Care Unit. When prolonged, however, continuous sedation may overlap with naturally occurring sleep periods and potentially increase the risk of sleep deprivation. We modified an established rat model of sleep to determine whether prolonged, continuous sedation results in sleep deprivation. Rats were continuously sedated for a 12-h period overlapping completely with their normal sleep phase. Electroencephalogram (EEG) and movement data were collected before and after the sedation period. Rats were evaluated for EEG and movement evidence of sleep deprivation after sedation. When compared with baseline, the time spent in rapid eye movement (REM) and non-REM sleep was decreased during the first 4 h after sedation. The duration of non-REM sleep bouts was not altered. Power in the delta band (0.5-4 Hz) during non-REM sleep was diminished during the first 2 h only. Movements were reduced during the first hour after emergence from sedation only. In summary, no EEG or behavioral evidence of sleep deprivation was observed on emergence from sedation. These results imply that sedation is associated with a restorative process reversing the natural accumulation of sleep need that occurs during wakefulness. IMPLICATIONS: Prolonged sedation in the Intensive Care Unit may alter the restorative effects of naturally occurring sleep. We sedated rats during their sleep phase to determine whether sedation interferes with sleep. Upon emergence, no evidence of sleep deprivation was observed. Sedation may thus be associated with a restorative effect similar to sleep.

Animals↗
PubMed2001

BIS monitoring to prevent awareness during general anesthesia.

BACKGROUND: Unexpected awareness is a rare but well-described complication of general anesthesia that has received increased scientific and media attention in the past few years. Transformed electroencephalogram monitors, such as the Bispectral Index monitor, have been advocated as tools to prevent unexpected recall. METHODS: The authors conducted a power analysis to estimate how many patients would be needed in an appropriately powered study to demonstrate the Bispectral Index monitor reduces awareness, as well as a cost analysis to assess the cost of using the monitor for this purpose alone. RESULTS: If unexpected recall is rare (1 in 20,000), it will require a large study to demonstrate that the monitor reduces awareness (200,000-800,000 patients), and the cost of using it for this purpose alone would be high ($400,000 per case prevented). If awareness is common (1 in 100), then the number of patients needed in a study to demonstrate that the monitor works becomes tractable (1,000-4,000 patients), and the cost of using the monitor for this purpose alone becomes lower ($2,000 per case prevented). Because there are reported cases of awareness despite Bispectral Index monitoring, the authors are certain that the effectiveness of the monitor is less than 100%. As the performance of the monitor decreases from 100%, the size of the study needed to demonstrate that it works increases, as does the cost of using it to prevent awareness. CONCLUSION: The contention that Bispectral Index monitoring reduces the risk of awareness is unproven, and the cost of using it for this indication is currently unknown.

Anesthesia, General↗
PubMed1997

A new biological assay for measuring cyanide in blood.

UNLABELLED: Clinical diagnosis of cyanide poisoning is complicated by the lack of an easy, convenient assay for cyanide concentration in blood. Therapy may be delayed with unconfirmed diagnosis because the conventional antidote to cyanide poisoning exposes patients to substantial risks. We developed a new spectrophotometric assay to measure cyanide by extraction into a sodium hydroxide trap, followed by the addition of exogenous methemoglobin as a colormetric indicator. Samples of blood from 15 healthy subjects and 5 patients who had received prolonged nitroprusside infusions were assayed. To optimize assay characteristics, methemoglobin concentrations, pH, temperature, incubation time, and buffer strengths were varied. Duplicate samples were assayed by using the polarographic method for assay validation. Over a range from 300 ng/mL to 7 microg/mL, the correlation between methods was r = 0.983. Interassay and intraassay variability were 5% and 2%, respectively. Samples drawn from the five patients and tested by using both methods yielded a correlation of r = 0.978. This new assay for cyanide in blood may greatly facilitate the diagnosis and treatment of cyanide ingestion. The use of methemoglobin as the colorimetric indicator in the assay contributes to its low cost and ease of use. IMPLICATIONS: Cyanide, an important factor in death from burn-related inhalation injury, is difficult and time-consuming to measure. We developed a new, rapid blood test for cyanide using methemoglobin as a colormetric indicator. A rapid, accessible test for cyanide may speed the diagnosis and treatment of cyanide poisoning.

Adult↗
PubMed1997

Indications for mechanical ventilation.

Indications for mechanical ventilation have evolved substantially since widespread use of ventilatory support began in the early 1960s. While the metabolic and blood-gas alterations that mandate institution of ventilatory support have remained unaltered, new noninvasive modes of ventilation have widened the therapeutic options available to patients in acute respiratory failure. An understanding of the effect of mechanical ventilation on other organ systems has clarified the role of mechanical ventilation in the treatment of conditions other than respiratory failure such as stroke or head injury. Studies in patients recovering from major surgery have better defined the benefits and risks of postoperative mechanical ventilation. Finally, a better understanding of disease processes has led to more prognostic information that can help physicians, patients, and families decide on limits to compassionate care. The proper use of mechanical ventilation in disease states that do not involve respiratory failure as their primary manifestation is also important in light of the risks of respiratory support. In patients with CNS injury, the role of hyperventilation is limited to acute control of dangerous elevations of intracranial pressure. Although hypocarbia has been proposed to improve regional cerebral blood flow, studies have not demonstrated an improvement in outcome, suggesting that the risks of intubation, tracheal stimulation, sedation, and inability to examine the mental status outweigh any benefit. Some evidence suggests a detrimental effect from prolonged hyperventilation. The use of mechanical ventilation in postoperative care is another area that requires scrutiny. Numerous studies have shown that with coordination of care between surgeons, anesthesiologists, and nurses, many patients can be extubated significantly sooner than in the past. As techniques for administering anesthesia, performing surgery, and managing pain and mild respiratory insufficiency improve, knowledge in this area will continue to develop. Finally, the relation between mechanical ventilation, quality of life, and patient autonomy has come to play a greater role as the population ages. In many situations, respiratory failure represents the end stage of an irreversible disease. Whereas respiratory failure secondary to pulmonary contusion in young patients does not indicate a poor outcome, progressive respiratory failure in cystic fibrosis or following bone marrow transplantation usually represents a preterminal event. Understanding the epidemiology of respiratory failure in different disease categories is important to physicians, patients, and families in making informed decisions about their care. Mechanical ventilation represents a vital, fundamental form of life support. As the diseases, tools, and treatments change in anesthesia and critical care, careful definition of the role of mechanical ventilation in specific diseases, the route by which it is delivered, and the ability of such a form of life support to affect outcome will continue to be necessary.

Anesthesia, General↗
PubMed1995

Patients requiring sedation.

Recent advances in the pharmacology of sedative drugs have expanded their use in the intensive care unit. Indications and endpoints for sedation, however, often are defined poorly and are difficult to assess. Nevertheless, the complications of sedative drug administration are real. New indications for sedation have been proposed in recent years, including enforcing sleep/wake cycles, manipulating cellular metabolism, and preventing myocardial ischemia. The evidence supporting the efficacy of these new indications is not yet complete.

Procedural Sedation↗
PubMed1981

Acute and chronic effects of intrathecal morphine in monkeys.

In a double-blind study, seven Macaca fascicularis monkeys receiving intrathecal (i.t.) morphine in saline, 0.07 mg kg-1, were compared with a control group of four monkeys receiving either lumbar puncture alone (n = 1) or i.t. saline (n = 3). Neither morphine nor saline solutions contained preservatives. Arterial blood gas tensions, respiration, arterial pressure, e.c.g., state of consciousness and motor function were recorded for 24 h. The control group was sacrificed 42 days later and the study group was sacrificed at 6 (n = 2) or 42 days (n = 5) after injection. The central nervous system, meninges, nerve roots and dorsal root ganglia were examined macroscopically and microscopically. Respiratory depression did not occur in either the control or the study groups. There were moderate but statistically significant decreases in systolic and diastolic arterial pressures following i.t. morphine. In both groups, the pathological findings were localized to the cauda equina region and characterized by mononuclear cell infiltration. In neither group was there evidence of demyelination, arachnoiditis or necrosis. Focal endoneurial fibrosis was found in only one animal in the control group following multiple lumbar punctures associated with paraesthesia. The features appeared to correlate with the physical trauma associated with lumbar puncture rather than with the injectate.

Animals↗