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Biomedical subjects

P L Bailey

Publications and source records attributed to P L Bailey.

At least 37 records · Page 2Linked to original sources
PubMed1993

Fentanyl-induced rigidity and unconsciousness in human volunteers. Incidence, duration, and plasma concentrations.

BACKGROUND: Muscle rigidity frequently accompanies induction of anesthesia with opioids. The authors sought to determine whether unconsciousness and amnesia occur when humans develop rigidity and apnea after intravenous fentanyl (without other concomitant anesthetics). METHODS: The incidence and duration of rigidity and level of consciousness were evaluated and associated plasma concentrations of fentanyl were measured in 12 healthy adult male volunteers given only intravenous fentanyl. Fentanyl was infused at a rate of 150 micrograms/min until a total of 15 micrograms/kg had been administered. Arterial blood samples for fentanyl assay were drawn and responsiveness, heart rate (HR), and systolic and diastolic arterial blood pressures were determined at frequent intervals during and after infusion. If rigidity was accompanied by an Spo2 < 90%, positive pressure ventilation with 100% O2 with a mask was instituted until spontaneous ventilation resumed. RESULTS: The incidence of muscular rigidity was 50% (6/12). All subjects who developed rigidity were apneic, unresponsive, and had no recall of commands to breathe or of positive pressure ventilation. Subjects not developing rigidity remained awake and responsive. No subject developing rigidity required neuromuscular blockade to allow positive pressure ventilation and adequate oxygenation (Spo2 > 90%). When rigidity occurred, it started 3 +/- 0.9 (range 1-4) min after the peak plasma fentanyl concentration and lasted for 11.5 +/- 5.8 (range 7-23) min. Rigidity started at a plasma fentanyl concentration of 21.5 +/- 4.4 (range 16-28) ng/ml and ended at 6.9 +/- 1.5 (range 5.2-8.7) ng/ml. Baseline HR was less in the subjects who subsequently developed rigidity (56.7 +/- 7.8 vs. 67.2 +/- 7.8 P = 0.04). No differences in fentanyl plasma concentrations or predicted effect site concentrations for rigidity were detected between subjects who developed rigidity and those who did not. CONCLUSIONS: These findings support the hypothesis that unconsciousness occurs in the unstimulated subject during fentanyl-induced apnea and rigidity.

Adult↗
PubMed1993

Dose-response pharmacology of intrathecal morphine in human volunteers.

BACKGROUND: Intrathecal morphine sulfate (ITMS) administration was introduced into clinical practice in 1979. Inadequate information exists delineating ITMS respiratory effects in the dosage range most frequently employed today. This study evaluated 0.2, 0.4, and 0.6 mg ITMS in male volunteers. METHODS: Twenty healthy, young, adult male volunteers received 0.0, 0.2, 0.4, or 0.6 mg preservative-free ITMS in an isobaric solution administered at the L3-L4 interspace in a double-blind randomized fashion. Respiratory function was assessed by finger pulse oximetry (SpO2), respiratory rate, and arterial blood gas analysis via an indwelling arterial catheter and the slope of the ventilatory response to carbon dioxide (VE/CO2). Analgesia was assessed by the effect of ITMS on moderate pain produced by pressure algometry at the tibia. The need for supplemental oxygen, 2 L/min via nasal cannulae, was determined by the failure of verbal and tactile prompts to maintain subjects' SpO2 > or = 85% on more than two occasions. Heart rate, arterial blood pressure, sedation level, pupil size, and the incidence of adverse effects also were documented. All the above measurements were made before and 30 min after ITMS, hourly for 11 h, and then every 2 h for 12 more h. RESULTS: ITMS produced significant dose-related decreases in SpO2. Mild desaturations (SpO2 > or = 85 and < 90%) occurred in 2 of 5, 3 of 5, and 4 of 5 subjects receiving 0.2, 0.4, and 0.6 mg ITMS, respectively. Moderate to severe desaturations (SpO2 < 85%) occurred in 0 of 5, 2 of 5, and 4 of 5 subjects receiving 0.2, 0.4, and 0.6 mg ITMS, respectively. The need for supplemental oxygen also was significantly related to ITMS dose, with 0 of 5, 1 of 5, and 4 of 5 subjects requiring oxygen after 0.2, 0.4, and 0.6 mg ITMS, respectively. Nasal oxygen administration consistently alleviated hypoxemia. Increases in arterial carbon dioxide tension (PaCO2) and decreases in pH were significantly related to ITMS dose. Peak mean PaCO2s were 42.4, 44.9, and 50.7 mmHg in the 0.2-, 0.4-, and 0.6-mg groups, respectively. These peaks occurred 6.5-7.5 h after ITMS injection. ITMS produced significant dose-related depression of VE/CO2. Maximum mean depressions of VE/CO2 were to 61%, 63%, and 32% of baseline in the 0.2-, 0.4-, and 0.6-mg groups, respectively. These nadirs occurred 3.5-7.5 h after ITMS injection. Some subjects receiving 0.6 mg ITMS experienced profound (< 20% of baseline) and prolonged (< 50% of baseline for up to 20 h) VE/CO2 depression. Magnitude and duration of analgesia after ITMS were dose-related. Changes in heart rate, systolic blood pressure, and respiratory rate were not significantly related to ITMS dose. Hypoxemia was not related to respiratory rate. Although ITMS produced statistically significant dose-related increases in sedation and decreases in pupil size, these changes were small and did not coincide with hypoxemia. ITMS caused dose-related increases in emesis, but the severity of pruritus and urinary retention was unrelated to dose. CONCLUSION: ITMS produced dose-related analgesia and respiratory depression in nonsurgical healthy, young, adult male volunteers. Respiratory depression was significant after 0.2 or 0.4 mg and profound and prolonged after 0.6 mg. No clinical signs or symptoms, including respiratory rate, reliably indicated hypoxemia. Pulse oximetry reliably detected hypoxemia after ITMS, and supplemental nasal oxygen (2 L/min) effectively corrected this hypoxemia.

Adult↗
PubMed1992

Fentanyl and sufentanil increase intracranial pressure in head trauma patients.

Although opioids frequently are administered to patients with severe head trauma, the effects of such drugs on intracranial pressure are controversial. Nine patients with severe head trauma were studied for the effects of fentanyl and sufentanil on intracranial pressure (ICP). In all patients, ICP monitoring was instituted before the study. Full neuromuscular blockade was achieved with vecuronium bromide before the administration of either fentanyl (3 micrograms.kg-1) or sufentanil (0.6 microgram.kg-1) as an intravenous bolus over a 1-min period in a masked and random fashion. Patients received the other opioid in the same fashion 24 h later. Arterial blood pressure, heart rate, and ICP were recorded continuously for the 1 h after drug administration. Fentanyl was associated with an average ICP increase of 8 +/- 2 mmHg, and sufentanil with an increase of 6 +/- 1 mmHg. These increases were statistically significant. Both drugs produced clinically mild decreases in mean arterial blood pressure (fentanyl, 11 +/- 6 mmHg; sufentanil, 10 +/- 5 mmHg) that nevertheless were statistically significant. No significant changes in heart rate occurred. These results indicate that modest doses of potent opioids can significantly increase ICP in patients with severe head trauma.

Adult↗
PubMed1991

Respiratory effects of clonidine alone and combined with morphine, in humans.

Because only limited and controversial data exist concerning the respiratory effects of clonidine in humans, the authors evaluated the respiratory effects of clonidine alone and in combination with morphine, in 12 healthy adult males. Subjects received clonidine (0.3-0.4 mg orally), morphine (0.21 mg/kg intramuscularly), or the same doses of the two drugs combined, at three separate sessions in a randomized fashion. The study was balanced for all possible sequences of drug administration. Blood pressure, heart rate, hemoglobin oxygen saturation via finger pulse oximetry, and ventilatory and occlusion pressure responses to CO2 were obtained before and 20, 40, 60, 90, 120, 180, 240, 300, and 360 min after administration of drug or drug combination. Systolic blood pressure decreased significantly only in the clonidine and clonidine plus morphine groups (P less than 0.05). Hemoglobin oxygen saturation decreased by a statistically significant (P less than 0.05), though clinically minor, degree only in the morphine or morphine plus clonidine groups. Clonidine alone did not depress the slope of either the ventilatory or the occlusion pressure response to CO2. In addition, clonidine did not significantly worsen morphine-induced depression of the slope of the ventilatory and occlusion pressure responses in the drug combination group. Both the ventilatory and occlusion pressure responses to CO2 were shifted to the right in all three drug groups (P less than 0.05) but were shifted to a significantly lesser degree by clonidine alone than by morphine and morphine plus clonidine. In healthy young adult males, clonidine alone produces little respiratory depression and does not significantly potentiate morphine-induced respiratory depression.

Adolescent↗
PubMed1990

Transdermal scopolamine reduces nausea and vomiting after outpatient laparoscopy.

The authors evaluated the effect of transdermal scopolamine on the incidence of postoperative nausea, retching, and vomiting after outpatient laparoscopy in a double-blind, placebo-controlled study. A Band-Aid-like patch containing either scopolamine or placebo was placed behind the ear the night before surgery. Anesthesia was induced with fentanyl (0.5-2 micrograms/kg iv), thiopental (3-5 mg/kg iv), and succinylcholine (1-1.5 mg/kg iv) and maintained with isoflurane (0.2-2%) and nitrous oxide (60%) in oxygen. Scopolamine-treated patients had less nausea, retching, and vomiting compared with placebo-treated patients (P = 0.0029). Severe nausea and/or vomiting was present in 62% of the placebo group but only 37% of those getting the scopolamine patch. Repeated episodes of retching and vomiting were also less frequent in the scopolamine group compared with the placebo group (23% vs. 41%; P = 0.0213) as was the need for additional antiemetic therapy (13% vs. 32%; P = 0.0013). Patients in the scopolamine group were also discharged from the hospital sooner (4 +/- 1.3 vs. 4.5 +/- 1.5 h; P = 0.0487). Side effects were more frequent among those patients treated with the scopolamine patch (91% vs. 45%; P less than 0.05) but were not troublesome. The authors conclude that transdermal scopolamine is a safe and effective antiemetic for outpatients undergoing laparoscopy.

Administration, Cutaneous↗
PubMed1990

Frequent hypoxemia and apnea after sedation with midazolam and fentanyl.

More than 80 deaths have occurred after the use of midazolam (Versed), often in combination with opioids, to sedate patients undergoing various medical and surgical procedures. We investigated the respiratory effects of midazolam (0.05 mg.kg-1) and fentanyl (2.0 micrograms.kg-1) in volunteers. The incidence of hypoxemia (oxyhemoglobin saturation less than 90%) and apnea (no spontaneous respiratory effort for 15 s) and the ventilatory response to carbon dioxide were evaluated. Midazolam alone produced no significant respiratory effects. Fentanyl alone produced hypoxemia in half of the subjects and significant depression of the ventilatory response to CO2, but did not produce apnea. Midazolam and fentanyl in combination significantly increased the incidence of hypoxemia (11 of 12 subjects) and apnea (6 of 12 subjects), but did not depress the ventilatory response to CO2 more than did fentanyl alone. Adverse reactions linked to midazolam and reported to the Department of Health and Human Services highlight apnea- and hypoxia-related problems as among the most frequent adverse reactions. Seventy-eight per cent of the deaths associated with midazolam were respiratory in nature, and in 57% an opioid had also been administered. All but three of the deaths associated with the use of midazolam occurred in patients unattended by anesthesia personnel. We conclude that combining midazolam with fentanyl or other opioids produces a potent drug interaction that places patients at a high risk for hypoxemia and apnea. Adequate precautions, including monitoring of patient oxygenation with pulse oximetry, the administration of supplemental oxygen, and the availability of persons skilled in airway management are recommended when benzodiazepines are administered in combination with opioids.

Adolescent↗
PubMed1990

Is there central respiratory depression after intravenous administration of propranolol?

Beta-adrenergic blockers have been reported to depress central ventilatory drive. The authors investigated this possibility in a double-blind, randomized fashion in 12 healthy volunteers who received 0.1 mg.kg-1 of propranolol and normal saline intravenously at two separate study sessions. A modified Read rebreathing technique was used. Both ventilatory and occlusion pressure responses to CO2 were measured to help separate peripheral (airway) from central mechanisms. Significant beta blockade was demonstrated by statistically lower heart rate responses to CO2 rebreathing after propranolol, but not normal saline. Nevertheless, propranolol exerted no significant effect on resting end-tidal CO2 or the ventilatory and occlusion pressure responses to CO2. Although health subjects appear to have minimal alterations in their ventilatory response to CO2 after beta-adrenergic blockade, patients with airway disease may still experience significant changes in ventilation. In addition, drug interaction studies may give further insight into the presence or absence of any respiratory effects of propranolol.

Adult↗
PubMed1990

Central neurogenic hyperventilation: pharmacologic intervention with morphine sulfate and correlative analysis of respiratory, sleep, and ocular motor dysfunction.

Central neurogenic hyperventilation (CNH), for which there is no effective therapy, can eventually result in respiratory fatigue and death. This report describes a patient with CNH due to a brainstem anaplastic astrocytoma who also exhibited disturbances of sleep and ocular motor function. The CNH responded clinically to morphine sulfate and methadone. Analysis of ventilatory response to CO2 before and after morphine demonstrated a depression of ventilatory response (49 to 53% of baseline) and occlusion pressure response (35 to 50% of baseline) to CO2, with a requirement for high doses of naloxone (10 mg IV) to reverse the effect. Polysomnography revealed sustained hyperventilation, elevated O2 saturation, and low end-tidal CO2 throughout all stages of non-rapid eye movement (NREM) sleep, and absence of rapid eye movement (REM) sleep. Ocular motor evaluation disclosed absence of horizontal and reflexive saccades with compensatory head thrusts. Correlation of the clinical and physiologic data with the MRI abnormalities suggested that the lesion responsible for CNH in this patient might reside in the medial tegmental parapontine reticular formation. Since recurrent episodes of hyperventilation responded in a sustained fashion to IV and oral opiates, this treatment may warrant consideration in other patients with CNH.

Adult↗
PubMed1990

Differences in magnitude and duration of opioid-induced respiratory depression and analgesia with fentanyl and sufentanil.

The magnitude and duration of analgesia and respiratory depression induced by fentanyl (1.0, 2.0, and 4.0 micrograms/kg) and sufentanil (0.1, 0.2, and 0.4 microgram/kg) after intravenous administration over 30 s were measured in 30 healthy young adult male volunteers divided into three groups and studied in a double-blind, randomized fashion. Each volunteer received one dose of fentanyl or sufentanil and no sooner than 48 h later, the corresponding equipotent dose of the other opioid. End-tidal CO2 and ventilatory and occlusion pressure responses to CO2 rebreathing were used to measure drug-induced respiratory effects. Analgesic effects were assessed by changes in the pain threshold to electric shock applied to the forearm. Plasma levels of fentanyl and sufentanil were measured by radioimmunoassay. Testing and sampling intervals were 5, 30, 60, 90, 120, 240, 300, and 360 min after drug administration. The magnitude and duration of depression of the ventilatory and occlusion pressure response were significantly less with sufentanil compared with fentanyl, irrespective of dose. Ventilatory and occlusion pressure responses returned to control values by 30 and 30 min, respectively, after sufentanil and by 240 and 120 min, respectively, after fentanyl. Statistically significant elevations of the pain threshold were, however, greater and longer lasting after sufentanil compared with fentanyl. Pain threshold returned to control values 180 min after sufentanil but only 90 min after fentanyl. These results suggest that sufentanil may provide better patient comfort with less respiratory depression than does fentanyl.

Adolescent↗
PubMed1989

Oral transmucosal fentanyl citrate (lollipop) premedication in human volunteers.

The authors determined whether fentanyl incorporated into a candy lollipop, oral transmucosal fentanyl citrate (OTFC), would cross mucosal tissues of the mouth in sufficient quantities during and after dissolution to produce sedation and/or analgesia. Associated respiratory and circulatory changes, side effects, and plasma concentrations of fentanyl were also measured. The evaluations were done in 28 adult volunteers who received fentanyl citrate in doses of 5, 4, 2, 1, and 0.5 mg in OTFC and rapidly sucked the lollipops (N = 20) or allowed them to passively dissolve (N = 8). Rapid consumption of OTFC resulted in more rapid onset of a pleasant feeling (first subjective sensation) but not more rapid onset of objective sedation or analgesia than passive dissolution. There was a significant correlation between dose of OTFC and magnitude of sedation (P less than 0.001, Spearman rank correlation = -0.82). Higher doses of OTFC produced greater and longer lasting analgesia and respiratory depression and a higher incidence of nausea and vomiting than lower doses, but pruritus (33%-87%) was not related to the dose of OTFC. Heart rate and arterial blood pressures were not changed by any dose of OTFC. The data indicate that low doses of OTFC (0.5 and 1 mg, equivalent to 5-20 micrograms.kg-1 of fentanyl citrate) produce analgesia and sedation with minimal side effects and little respiratory depression in adult volunteers and deserve further evaluation in patients.

Absorption↗
PubMed1987

Is fentanyl an anesthetic in the dog?

The authors used the absence of vocalization and movement during application of a hemostat clamped to the first ratchet at the base of the tail as an indication of anesthesia for evaluation of the anesthetic properties of fentanyl in the dog. Eighty-six unpremedicated, unrestrained, untrained mongrel dogs were given one of eight doses of fentanyl citrate (125, 250, 500, 750, 1000, 1500, 2000, and 3000 micrograms/kg) as a single intravenous bolus injection. Dogs breathed spontaneously without oxygen supplementation. Anesthesia was assessed every 5 min until absence of anesthesia was recorded for two consecutive evaluations. Venous plasma samples were obtained in two or three dogs receiving each of the doses of fentanyl 5 min after fentanyl injection and again when application of the tail clamp elicited either vocalization or movement (positive response). Fentanyl resulted in recumbency in all animals except two receiving 125 micrograms/kg. Although all doses of fentanyl produced anesthesia in at least one animal 5 min after injection, the duration of anesthesia was short, responses unpredictable, and anesthesia achieved in all animals only with a dose of 3000 micrograms/kg. Increasing doses of fentanyl resulted in higher plasma fentanyl concentrations 5 min after injection and at the time of the first positive response to tail clamp but there was great variability. All doses of fentanyl caused statistically significant decreases in heart and respiratory rates but none produced apnea or a PaCO2 higher than 67 mm Hg.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia, Intravenous↗
PubMed1987

Antagonism of postoperative opioid-induced respiratory depression: nalbuphine versus naloxone.

The authors compared naloxone and nalbuphine as antagonists of opioid-induced respiratory depression to determine the relative efficacies and safety of the two agents. In a double-blind, randomized fashion, 90 anesthetized patients received a mean dose of 25 micrograms/kg fentanyl during surgery. Inadequate spontaneous respirations at the end of anesthesia were treated with either naloxone 0.08 mg or nalbuphine 2.5 mg IV every 2 min while heart rate (HR), systolic and diastolic blood pressures (SBP, DBP), respiratory rate (RR), and tidal volume (TV) were measured at 2-min intervals. Arterial blood samples for analysis of PaCO2, PaO2, and pH were drawn when spontaneous ventilation resumed, and 30 and 60 min later. Narcotic antagonism and respiration were deemed adequate when TV was greater than or equal to 4 ml/kg and RR greater than or equal to 8 breaths/min. Heart rate, SBP, DBP, TV and RR were recorded, as were the occurrence of renarcotization (RR less than 8) and analgesic requirements every 5 min during the recovery room stay. Sixty of 90 patients required narcotic antagonism at the end of surgery. No patient required more than three doses (0.24 mg) of naloxone or four doses (10 mg) of nalbuphine. Both antagonists produced similar and moderate increases in SBP and HR while restoring adequate spontaneous ventilation. There were no significant differences in TV, RR, or arterial blood gases (ABGS) between the two groups after narcotic reversal.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗