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R B Weiskopf

Publications and source records attributed to R B Weiskopf.

At least 55 records · Page 3Linked to original sources
PubMed1994

The desflurane (Tec 6) vaporizer: design, design considerations and performance evaluation.

We have described the design and design considerations of the desflurane Tec 6 "vaporizer" and have tested its performance characteristics. The vaporizer differs from previous vaporizers designed for anaesthesia in that electromechanical rather than mechanical controls accommodate the different physical characteristics of desflurane. This design, while offering perhaps an increased risk of failure (owing to sophisticated electronic components and circuitry), on the other hand offers the decreased likelihood of accidental delivery of very large concentrations of liquid anaesthetic resulting from tilting or overfilling and alarms and warnings not previously incorporated into the design of anaesthetic vaporizers. The output characteristics of the vaporizer are as expected, based on the design: desflurane concentration output in oxygen has accuracy (+/- 15%) which is similar to that of the mechanical vaporizers; output decreases when nitrous oxide is added owing to the lower viscosity, but remains within 20% of the dial setting or 0.5% absolute.

Anesthesia, Inhalation↗
PubMed1994

Humans anesthetized with sevoflurane or isoflurane have similar arrhythmic response to epinephrine.

BACKGROUND: Anesthetics can alter the dose of exogenously administered epinephrine that causes cardiac arrhythmias. The purpose of this study was to test the hypothesis that in humans anesthetized with sevoflurane, the arrhythmic response to epinephrine is not different from the response in humans anesthetized with isoflurane. METHODS: We determined the arrhythmogenicity of submucosally administered epinephrine in 40 ASA physical status 1 or 2 patients who were to undergo transsphenoidal surgery. Patients were assigned randomly to be given 1.0-1.3 minimum alveolar concentration sevoflurane or isoflurane. A surgeon, blinded to the anesthetic and the concentration of epinephrine, injected into the nasal submucosa epinephrine 10, 13.3, or 20 micrograms/ml in saline of volume sufficient for surgical need. We defined a "positive" response as three or more premature ventricular contractions within 5 min after initiation of injection. Responses between anesthetic groups within each dose range of epinephrine were compared by chi-squared analysis. RESULTS: No patient given either anesthetic developed premature ventricular contractions with doses of epinephrine less than 5 micrograms/kg. At larger doses of epinephrine (5-9.9 and 10-14.9 micrograms/kg), the frequency of arrhythmias did not differ between patients given sevoflurane and patients given isoflurane. Patients anesthetized with 1.2 minimum alveolar concentration sevoflurane had blood pressure similar to and heart rate less than those of patients anesthetized with similar concentrations of isoflurane. Blood pressure and heart rate were increased similarly in both groups after laryngoscopy and tracheal intubation and after epinephrine injection. CONCLUSIONS: Sevoflurane and isoflurane do not differ in their sensitization of the human myocardium to the arrhythmogenic effect of exogenously administered epinephrine.

Adult↗
PubMed1994

Rapid increase in desflurane concentration is associated with greater transient cardiovascular stimulation than with rapid increase in isoflurane concentration in humans.

BACKGROUND: Increases in desflurane and isoflurane concentrations can transiently increase arterial blood pressure or heart rate or both during induction of anesthesia. The current study tested the hypothesis that a rapid increase of desflurane concentration in humans increases sympathetic activity and hormonal variables and heart rate and arterial blood pressure more than does an equivalent increase in isoflurane concentration. METHODS: Twelve healthy male volunteers were assigned randomly to receive desflurane and on a separate occasion isoflurane. After induction of anesthesia with propofol 2 mg/kg, anesthesia was maintained at 0.55 MAC (desflurane, 4.0%; isoflurane 0.71% end-tidal) for 32 min. Mechanical ventilation maintained normocapnia throughout anesthesia. Mean arterial blood pressure and heart rate were recorded continuously, and arterial blood was sampled for plasma catecholamine and vasopressin (AVP) concentrations, and plasma renin activity. Anesthetic concentration was increased rapidly to 1.66 MAC (desflurane, 12.0%; isoflurane 2.12% end-tidal), and maintained at this concentration for 32 min, and then rapidly decreased to and maintained at 0.55 MAC for an additional 32 min. RESULTS: Neither anesthetic produced sympathetic or cardiovascular stimulation during their initial rapid wash-in to 0.55 MAC. The rapid increase to 1.66 MAC increased mean arterial blood pressure, heart rate, and plasma epinephrine and norepinephrine concentrations, and plasma renin activity with both desflurane and isoflurane, the former usually producing a response of greater magnitude than the latter. Plasma AVP concentration increased with desflurane only. Increased mean arterial blood pressure returned to control in 4 min. Heart rate decreased 50% of the difference between its peak and the value at 32 min at 1.66 MAC in 2 min with desflurane and in 4 min with isoflurane but did not return to the value at 0.55 MAC with either anesthetic. With desflurane, plasma epinephrine and AVP concentrations decreased quickly from their peak values, remaining elevated for 8 min. Decrease of concentrations of desflurane and isoflurane from 1.66 MAC to 0.55 MAC rapidly decreased heart rate and increased mean arterial blood pressure with both anesthetics. Thirty-two minutes after return to 0.55 MAC, with both anesthetics, only heart rate remained increased relative to the values at 32 min of the initial period of 0.55 MAC anesthesia. CONCLUSIONS: In healthy male volunteers, rapid increases of desflurane or isoflurane from 0.55 to 1.66 MAC increase sympathetic and renin-angiotensin system activity, and cause transient increases in arterial blood pressure and heart rate. Desflurane causes significantly greater increases than isoflurane, and also causes a transient increase in plasma AVP concentration. The temporal relationships suggest that the increased sympathetic activity increases mean arterial blood pressure and heart rate, with mean arterial blood pressure also increased by increased plasma AVP concentration, whereas the delayed, increased plasma renin activity is likely a response to the ensuing hypotension, or earlier inhibition by AVP, or both.

Anesthesia, General↗
PubMed1994

Rapid 1% increases of end-tidal desflurane concentration to greater than 5% transiently increase heart rate and blood pressure in humans.

BACKGROUND: Large (0.5-1.0 MAC), rapid increases of desflurane to concentrations greater than 5% can transiently increase heart rate, mean arterial blood pressure (MAP), sympathetic nerve activity, and plasma epinephrine concentration. We tested the hypothesis that small (1% = 0.14 MAC), rapid increases of desflurane concentration to greater than 5% do not increase heart rate, blood pressure, and plasma catecholamine concentrations. METHODS: Anesthesia was induced with intravenous propofol, 2 mg/kg, in 13 healthy male volunteers, 19-33 yr of age, and ventilation was controlled to maintain normocapnia. We gave 4% end-tidal desflurane in oxygen for 32 min and then imposed successive 1% increases in end-tidal desflurane concentration, each new concentration maintained for 4 min, to a final concentration of 12%. We measured heart rate, MAP and plasma catecholamine concentrations in the awake state, after 4 min at each 1% step, and at times of peak increase of MAP (> or = 10% change). RESULTS: Increases in heart rate and blood pressure of more than 10% occurred with 1% step-increases in only 1 volunteer at 5% desflurane but in 7-10 (MAP) and 8-12 (heart rate) of the 13 volunteers at higher desflurane concentrations. The 1% increases in desflurane concentration to greater than 5% also transiently increased plasma epinephrine concentrations but not vasopressin concentration or plasma renin activity in those volunteers in whom MAP increased. CONCLUSIONS: Small (1%) increases in desflurane concentration to and greater than 6% can transiently increase heart rate, mean arterial pressure, and plasma epinephrine concentration. These data and those from a previous study indicate that these increases occur with a lesser frequency and magnitude than those associated with a single, rapid step from 4% to 12% end-tidal desflurane.

Adult↗
PubMed1994

Repetitive rapid increases in desflurane concentration blunt transient cardiovascular stimulation in humans.

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.

Adult↗
PubMed1994

Fentanyl, esmolol, and clonidine blunt the transient cardiovascular stimulation induced by desflurane in humans.

BACKGROUND: A rapid increase in the end-tidal concentration of desflurane to greater than 1 MAC transiently increases heart rate, arterial blood pressure, and circulating epinephrine and vasopressin concentrations. We hypothesized that drugs that block sympathetic activity or decrease sympathetic outflow (an opioid, a beta-adrenergic antagonist, and an alpha 2-adrenergic agonist) would blunt these responses. METHODS: After induction of anesthesia with intravenous propofol 2 mg/kg in ten healthy male volunteers age 25 +/- 1 yr (mean +/- standard error), anesthesia was maintained with 4% end-tidal desflurane in oxygen (0.55 MAC) via an endotracheal tube for 32 min. Controlled ventilation provided normocapnia. We then increased the end-tidal desflurane concentration within 1 min to 8% (1.1 MAC) and maintained this concentration for 10 min. On separate days, five of these volunteers were similarly anesthetized except that 5 min before the increase to 8% desflurane, we administered intravenous fentanyl 1.5 micrograms/kg and on another day 4.5 micrograms/kg (dose randomly assigned). On 2 separate days, intravenous esmolol 0.75 mg/kg was given to five volunteers 1.5 min before, or clonidine 4.3 micrograms/kg by mouth to four volunteers 90 min before, the increase from 4% to 8% desflurane. RESULTS: Without pretreatment, the increase to 8% desflurane increased heart rate (from 57 +/- 2 to 118 +/- 6 beats/min at peak, mean +/- standard error) and mean arterial blood pressure (from 66 +/- 2 to 118 +/- 5 mmHg). At the time of peak hemodynamic changes (within 1-2 min of the increase in desflurane concentration), plasma epinephrine and norepinephrine concentrations increased (from 22 +/- 6 to 339 +/- 83 pg/ml and from 205 +/- 19 to 283 +/- 30 pg/ml, respectively). Fentanyl 1.5 and 4.5 micrograms/kg attenuated the heart rate increase by 61 +/- 14% and 70 +/- 7% and the mean arterial blood pressure increase by 31 +/- 16% and 46 +/- 11% but did not alter the epinephrine or norepinephrine response at the time of peak cardiovascular changes. Esmolol attenuated the heart rate response but no other response. Clonidine attenuated all responses except that of norepinephrine and also caused postanesthesia sedation. CONCLUSIONS: Fentanyl, esmolol, and clonidine blunt the transient cardiovascular response to a rapid increase in desflurane concentration. Fentanyl may be the most clinically useful of these drugs because it blunts the increase in heart rate and blood pressure, has minimal cardiovascular depressant effects, and imposes little postanesthetic sedation.

Adrenergic beta-Antagonists↗
PubMed1993

Arrhythmogenic doses of epinephrine are similar during desflurane or isoflurane anesthesia in humans.

BACKGROUND: Inhaled anesthetics can alter the arrhythmogenicity of exogenously administered epinephrine. Although swine anesthetized with desflurane or isoflurane do not differ in their arrhythmic response to exogenous epinephrine, the relative effect of epinephrine in the presence of these anesthetics in humans is untested. METHODS: The authors compared the arrhythmogenicity of submucosally administered epinephrine in 36 ASA physical status 1 and 2 patients undergoing transsphenoidal resection of pituitary tumors who were randomly assigned to receive 1.0-1.3 MAC desflurane or isoflurane anesthesia. A surgeon, blinded to the administered anesthetic and the concentration of epinephrine, injected 1:50,000, 1:75,000, or 1:100,000 (20, 13.3, or 10 micrograms/ml) epinephrine in saline of volumes sufficient for surgical need. The authors defined a positive response as three or more premature ventricular contractions (PVCs) in the 5 min after starting the injection. RESULTS: No patient given either anesthetic developed any PVCs with epinephrine doses less than 7.0 micrograms/kg. Greater doses of epinephrine (7.0-13.0 micrograms/kg) produced positive responses at equal frequencies in the two anesthetic groups. CONCLUSIONS: The authors concluded that isoflurane and desflurane do not differ in their sensitization of human myocardium to the arrhythmogenic effects of exogenously administered epinephrine.

Adolescent↗
PubMed1993

Comparing the costs of inhaled anesthetics.

BACKGROUND: The immediate cost of an inhaled anesthetic results from an interplay between four factors: (1) the cost per milliliter of liquid anesthetic, (2) the volume of vapor that results from each milliliter of liquid, (3) the effective potency of the anesthetic (what concentration must be delivered from a vaporizer to provide a clinically appropriate level of anesthesia), and (4) the background flow of the gases that is chosen. A background flow that supplies only the gases/vapors required (taken up) by the patient (a "closed circuit") produces the least cost but also the least control of anesthetic level, whereas a high flow prevents rebreathing (a non-rebreathing system) but produces the greatest cost and control. We define greater "control" as a smaller ratio of delivered to alveolar concentrations. A lower solubility of an anesthetic accords the same level of control at a lower background flow rate than is achieved at a higher background flow rate with a more soluble anesthetic. Thus, a poorly soluble anesthetic may be used with a lower background flow rate than a more soluble anesthetic and may offer greater control and/or decreased cost. METHODS: This report presents a method of determining the cost of inhaled anesthetic use. As an example, the cost of delivering a desflurane anesthetic is compared with that of delivering an isoflurane anesthetic, assuming both provide an alveolar concentration of 1 MAC. The comparison is based on the pharmacokinetic differences of the two anesthetics: taking into account that for a given therapeutic anesthetic concentration (MAC), for desflurane a lower flow rate of background gas is needed to produce similar control (relationship between delivered and alveolar gases) than is needed for isoflurane. RESULTS: The analysis demonstrates that the relative cost of administering the newer and less soluble anesthetic, desflurane, can be less than, greater than, or the same as the cost of administering isoflurane, depending on the background gas inflow rate selected. CONCLUSION: The manner in which inhaled anesthetics are used and their kinetic differences are important determinants of relative cost.

Administration, Inhalation↗
PubMed1992

Desflurane does not produce hepatic or renal injury in human volunteers.

We examined the potential toxicity of desflurane in 13 young 25.0 +/- 2.3 (mean +/- SD) yr-old men, given 7.35 +/- 0.81 MAC-hours of desflurane anesthesia. Hepatic and renal function tests, serum electrolytes, and standard urine and hematologic tests were performed before, during, and after anesthesia. No toxicity was found. There were no changes in tests of hepatocellular integrity (plasma alanine transferase activity), synthetic function (serum albumin, prothrombin time, partial thromboplastin time), or renal function (serum creatinine concentration, blood urea nitrogen concentration). Decreases in red blood cell count, hematocrit, and blood hemoglobin concentration during and immediately after anesthesia were attributed to blood sampling and infusion of intravenous electrolyte solution. These values returned by 4 days after anesthesia to values not different from those before anesthesia. Increased white blood cell counts and blood glucose concentrations noted during anesthesia with other inhaled anesthetics were also seen in these volunteers. Desflurane appears to have no greater toxicity than currently used inhaled anesthetics and, because of its lesser metabolism, may have lesser or not toxicity.

Adult↗
PubMed1991

The neuromuscular effects of desflurane, alone and combined with pancuronium or succinylcholine in humans.

The neuromuscular effects of desflurane administered alone were studied in ten healthy human volunteers aged 20-27 yr. Also, the dose-response relationships of pancuronium and succinylcholine in surgical patients during anesthesia with desflurane (n = 13) were compared to those during isoflurane anesthesia (n = 14). In the volunteers, we measured the mechanical response of the adductor pollicis muscle to stimulation of the ulnar nerve in a train-of-four (TOF) sequence at 2 Hz and at tetanic frequencies of 50, 100, and 200 Hz, each administered for 5 s. Amplitudes of the first response (T1) in each TOF sequence and the ratios of the fourth TOF response (T4) to the first were similar at 3, 6, and 9% desflurane and decreased significantly only at 12% (P less than 0.05). Desflurane concentrations of 3-12% caused tetanic fade (greater than 10% decrement in amplitude) at 50, 100, and 200 Hz. The addition of N2O and the duration of anesthetic exposure did not alter desflurane's neuromuscular effects. The only neuromuscular variable influenced by CO2 was T1 amplitude, which decreased as arterial CO2 tension (PaCO2) increased. The doses of pancuronium that depressed T1 amplitude by 50% (ED50) were similar during anesthesia with 1.25 MAC desflurane, 10.5 +/- 2.8 micrograms/kg (mean +/- SD) and 1.25 MAC isoflurane, 12.3 +/- 5.0 micrograms/kg. The ED50 doses of succinylcholine were similar during anesthesia with desflurane 132 +/- 76 micrograms/kg and isoflurane 123 +/- 36 micrograms/kg. We conclude that desflurane significantly depresses neuromuscular function and augments the action of pancuronium and succinylcholine to a degree similar to that of isoflurane.

Adult↗
PubMed1991

Clinical characteristics of desflurane in surgical patients: minimum alveolar concentration.

Desflurane (formerly I-653) is a new inhalaticnal anesthetic with a promising pharmacokinetic profile that includes low solubility in blood and tissue, including fat. Since its lipid solubility is less than that of other volatile agents, it may have lower potency. Low solubility would be expected to increase the rate at which alveolar concentration approaches inspired concentration during induction as well as to increase the rate of elimination of desflurane from blood at emergence. We determined the minimum alveolar concentration (MAC) of desflurane in 44 unpremedicated ASA physical status 1 or 2 patients undergoing elective surgery. We prospectively studied four patient groups distinguished by age and anesthetic regimen: 18-30 versus 31-65 yr and desflurane in 60% N2O/40% O2 versus desflurane in O2. Anesthesia was induced with desflurane or desflurane in 60% N2O/40% O2. MAC was determined by a modification of Dixon's up-and-down method with increments of 0.5% desflurane. The MAC of desflurane in O2 was 7.25 +/- 0.0 (mean +/- SD) in the 18-30-yr age group, and 6.0 +/- 0.29 in the 31-65-yr group; the addition of 60% N2O reduced the MAC to 4.0 +/- 0.29 and 2.83 +/- 0.58, respectively. The median time from discontinuation of desflurane to an appropriate response to commands was 5.25 min. Desflurane appears to be a mild airway irritant but was well tolerated by all patients.

Adult↗
PubMed1991

The electroencephalographic effects of desflurane in humans.

The electroencephalographic (EEG) effects of a new inhaled anesthetic are of interest because of the potential of such agents to produce excitatory (convulsant) activity and because of the potential usefulness of the EEG as an indicator of anesthetic depth and cerebral activity. Accordingly, we examined the EEG in 12 healthy, young male volunteers during desflurane anesthesia. Each subject had a baseline recording and then steady-state exposure to 6, 9, and 12% (0.83, 1.24, and 1.66 MAC) desflurane in O2 alone, and to 3, 6, and 9% desflurane in O2 with 60% N2O. The sequence of doses and the presence of N2O were randomized. We used mechanical ventilation to maintain normocapnia at each dose level. We also tested the effects of hypercapnia secondary to spontaneous ventilation. Additionally, at 1.24 MAC, subjects' lungs were hyperventilated to a PCO2 of 25.8 +/- 0.7 mmHg and exposed to rhythmic, loud clapping to attempt to provoke excitatory phenomena. Finally, after at least 6 h exposure to desflurane, we repeated measurements at 0.83 and 1.66 MAC to assess possible tolerance. Four channels of EEG were monitored visually, and at each dose, a quantitative EEG analysis was performed. Desflurane produced EEG changes comparable to those observed with equipotent levels of isoflurane. No epileptiform activity was seen. Desflurane significantly suppressed EEG activity; prominent burst suppression was seen at 1.24 MAC and higher. Substitution of N2O for 0.42 MAC desflurane reduced the degree of EEG suppression relative to the equipotent administration of desflurane and O2. Quantitative EEG measures for the early doses and for the later, repeated exposures did not differ.

Adult↗
PubMed1991

Percutaneous loss of desflurane, isoflurane, and halothane in humans.

We studied the percutaneous losses of the new inhaled anesthetic, desflurane (I-653), and of isoflurane and halothane during anesthetic administration and elimination in seven healthy male volunteers. Anesthesia was induced and maintained with midazolam, thiopental, and fentanyl. We administered 70% N2O for 30 min, and then administered 2% desflurane, 0.4% isoflurane, and 0.2% halothane concurrently with 65% N2O for 30 min. Inspired, end-tidal, and mixed-expired gas samples were collected during administration of the volatile agents and for 5-7 days of elimination. The right arm and hand of each subject was enclosed in a sealed glass cylinder having a port at each end, one for sampling and both for flushing with N2 after anesthetic administration and every 15 min thereafter. We sampled gases from the cylinder during administration and for the 150 min of elimination and analyzed their anesthetic concentrations by gas chromatography. The surface area of the enclosed portion of the arm was measured, and the total body surface area was calculated. All values were normalized to (i.e., divided by) the end-tidal (alveolar) concentration at the end of administration. During administration, percutaneous loss of halothane was 3.5 times that of desflurane and 2 times that of isoflurane. During elimination, the loss of halothane was 6 times and 2 times greater than the loss of desflurane and isoflurane, respectively. Percutaneous loss of halothane significantly exceeded that of isoflurane. The elimination values included an estimate of elimination after 150 min. The percutaneous loss of each anesthetic was 2- to 3-fold greater during elimination than administration.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Depression of ventilation by desflurane in humans.

We studied the ventilatory effects of desflurane (formerly I-653) with and without N2O in healthy male volunteers. After insertion of venous and arterial (radial and pulmonary) catheters, baseline measurements of tidal volume (VT), respiratory rate (RR), ventilatory response to CO2, and arterial and mixed venous blood gases were made. Subjects were randomly assigned to receive either desflurane with O2 (n = 6) or with O2 and 60% N2O (n = 6). Anesthesia was induced by inhalation of desflurane followed by tracheal intubation without muscle relaxants. In each volunteer, at end-tidal concentrations totaling 0.83, 1.24, and 1.66 MAC, we repeated measurements of VT, RR, response to CO2, and arterial and mixed venous blood gases. As depth of anesthesia increased, VT significantly (P less than 0.05) decreased from 363 +/- 22 ml awake to 76 +/- 22 ml at 1.66 MAC without N2O and from 473 +/- 70 ml awake to 128 +/- 6 ml at 1.66 MAC with N2O (mean +/- SE). Similarly, RR increased from 15 +/- 0.5 breaths per min awake to 32 +/- 2 breaths per min at 1.66 MAC without N2O and from 14 +/- 0.5 breaths per min awake to 40 +/- 3 breaths per min at 1.66 MAC with N2O. Desflurane without N2O depressed the ventilatory response to CO2 to 45 +/- 9, 31 +/- 5, and 11 +/- 4% of the awake values at 0.83, 1.24, and 1.66 MAC, respectively. With N2O, values were 52 +/- 14, 23 +/- 5, and 26 +/- 9% of the awake value at 0.83, 1.24, and 1.66 MAC, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Kinetics of desflurane, isoflurane, and halothane in humans.

The low solubility of desflurane in blood and tissues suggests that the partial pressures of this agent in blood and tissues should approach the inspired partial pressure more rapidly than would the blood and tissue partial pressures of other potent inhaled anesthetics. We tested this prediction, comparing the pharmacokinetics of desflurane with those of isoflurane, halothane, and nitrous oxide in eight volunteers. We measured the rate at which the alveolar (endtidal) (FA) concentration of nitrous oxide increased towards an inspired (FI) concentration of 65-70%, and then measured the concurrent increase in FA and mixed expired concentrations (FM) of desflurane, isoflurane, and halothane at respective FI values of 2.0%, 0.4%, 0.2%. Minute ventilation (VE) was measured concurrently with the measurements of anesthetic concentrations. The potent vapors were administered for 30 min; administration of nitrous oxide continued throughout the period of anesthesia. For the potent agents, we also measured VE, FA, and FM for 5-7 days of elimination. We used FA/FI and FA/FA0 (FA0 = the last FA during the administration of each anesthetic) to define the rate of increase of anesthetic in the lungs and the rate of elimination of anesthetic, respectively. FA/FI values at 30 min of administration were: (mean +/- SD) nitrous oxide 0.99 +/- 0.01, desflurane 0.90 +/- 0.01, isoflurane 0.73 +/- 0.03, and halothane 0.58 +/- 0.04. FA/FA0 values after 5 min of elimination were: desflurane 0.14 +/- 0.02, isoflurane 0.22 +/- 0.02, and halothane 0.25 +/- 0.02. Recovery (volume of anesthetic recovered during elimination per volume taken up) of desflurane (105 +/- 25%) equalled recovery of isoflurane (102 +/- 13%) and exceeded recovery of halothane (64 +/- 9%). Time constants for a five-compartment mammillary model for halothane and isoflurane differed for the lungs, fat group, and hepatic metabolism, and exceeded those for desflurane for all compartments. In summary, we found that FA/FI of desflurane increases more rapidly and that FA/FA0 decreases more rapidly in humans than do these variables with other available potent anesthetics. We also found that desflurane resists biodegradation in humans and so may have little or no toxic potential.

Adult↗
PubMed1991

Comparison of percutaneous losses of sevoflurane and isoflurane in humans.

We studied the percutaneous losses of sevoflurane and isoflurane during administration and elimination in seven healthy male volunteers. Anesthesia was induced and maintained with fentanyl, midazolam, and/or thiopental, and nitrous oxide for 30 min, after which 1% sevoflurane and 0.4% isoflurane in 65% nitrous oxide were administered for 30 min. Inspired, end-tidal, and mixed-expired gas samples were collected during administration and for 5-7 days of elimination. To measure percutaneous loss, each subject's arm was enclosed in a glass cylinder sealed at both ends and with two ports, one for flushing with nitrogen and one for obtaining gas samples during the 30 min of administration and the first 150 min of elimination. Anesthetic concentrations in all samples were determined using gas chromatography. The surface area of the arm was measured and the total surface area was calculated. During administration and elimination, percutaneous loss of isoflurane was significantly greater than that of sevoflurane (P less than 0.05). For both volatile agents, losses during elimination were greater than during administration (P less than 0.05), but even when combined, these losses were too small to affect kinetic or metabolic studies based on mass balance.

Adult↗
PubMed1991

Comparison of kinetics of sevoflurane and isoflurane in humans.

The low solubility of sevoflurane in blood suggests that this agent should enter and leave the body more rapidly than isoflurane. However, the closeness of sevoflurane and isoflurane tissue/blood partition coefficients suggests that the rates of equilibration with and elimination from tissues should be similar. We tested both predictions, comparing sevoflurane with isoflurane and nitrous oxide in seven volunteers. We measured the rate at which the alveolar (end-tidal) (FA) concentration of nitrous oxide increased toward an inspired (FI) concentration of 65%-70%, then measured the concurrent rise in FA and mixed expired concentrations (FM) of sevoflurane and isoflurane at respective FI values of 1.0% sevoflurane and 0.6% isoflurane for 30 min. Minute ventilation (VE) was measured concurrently with the measurements of anesthetic concentrations. For the potent agents, we also measured VE, FA, and FM for 6-7 days of elimination. FA/FI values at 30 min of administration were as follows: nitrous oxide, 0.986 +/- 0.003 (mean +/- SD); sevoflurane, 0.850 +/- 0.018; and isoflurane, 0.733 +/- 0.027. FA/FA0 (FA0 = the last FA during administration) values after 5 min of elimination were as follows: sevoflurane, 0.157 +/- 0.020; isoflurane, 0.223 +/- 0.024. Recovery (volume of anesthetic recovered during elimination/volume taken up) of sevoflurane (101% +/- 7%) equaled recovery of isoflurane (101% +/- 6%). Time constants for a five-compartment mammillary model for sevoflurane were smaller than those for isoflurane for the lungs but were not different from isoflurane for the other compartments.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Inhalation↗