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Biomedical subjects

C C Hug

Publications and source records attributed to C C Hug.

At least 55 records · Page 3Linked to original sources
PubMed1989

Wheal and flare responses to opioids in humans.

Certain opioids release histamine from cutaneous mast cells to produce local wheal and flare responses and adverse hemodynamic effects. In vivo responses to opioids suggest that cutaneous responses result from the interaction of opioids with opioid receptors on human mast cells. There are no data evaluating or comparing the opioids currently used in anesthesia. Volunteers were injected intradermally with different opioids as well as with naloxone and antihistamines to evaluate their effects on cutaneous mast cell reactivity and cutaneous vascular responses. Fentanyl and morphine produced concentration-dependent wheal and flare responses in the range of 5 X 10(-6) M to 1.5 X 10(-3) M. Volunteers were then tested intradermally with different opioids and histamine at a 5 X 10(-4) M concentration to determine their relative cutaneous effects. Morphine, meperidine, fentanyl, and sufentanil produced both wheal and flare responses that were significantly greater than those due to saline (P less than 0.05). Naloxone, alfentanil, and nalbuphine did not produce significant wheal or flare responses. Butorphenol was followed by a significant wheal but no flare. Naloxone attentuated cutaneous wheal and flare responses to fentanyl and the flare response to morphine. Intradermal antihistamines (diphenhydramine and cimetidine) produced significant wheal and flare responses. Electron micrographs of biopsies from fentanyl-induced wheals demonstrated normal mast cell architecture with no evidence of mast cell degranulation. Opioid effects on wheal and flare responses and mast cell degranulation appear independent of opioid analgesic potency. Opioids produce cutaneous vascular responses dependent on both histamine release from mast cells and direct effects on the vasculature.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Cutaneous↗
PubMed1988

Pharmacokinetics and pharmacodynamics of midazolam in the enflurane-anesthetized dog.

Midazolam (Mid) is widely used as an anesthetic adjunct. To test its anesthetic effect vs. concentration relationships, it is desirable to establish stable and predictable Mid concentrations in plasma (and brain). Therefore, the pharmacokinetics of Mid in the enflurane-anesthetized dog were determined, and the ability of Mid to reduce the enflurane concentration required for anesthesia was measured and correlated with the Mid concentration in plasma [MID]. Mongrel dogs (n = 9) were anesthetized with enflurane and the enflurane EC50 (MAC--the end-tidal concentration at which one-half of the dogs respond to the noxious stimulation of clamping of the tail, and one-half do not) was determined. Group 1 (n = 5) received Mid 2.5 mg/kg iv over 60 sec. Plasma for determination of [MID] was collected and the enflurane EC50 was determined repeatedly over the 7-8-hr period following injection. Based on the pharmacokinetic parameters determined for Group 1, dogs in Group 2 (n = 4) received Mid as a continuous infusion of 21 micrograms kg-1 min-1 for 5 hr accompanied by an initial loading dose (3 mg/kg infused over 20 min) designed to produce a stable [MID] of 1000 ng/ml in plasma. Enflurane MAC and [MID] were determined regularly during the infusion and for 6 hr after discontinuation of the infusion. There were no important differences in the pharmacokinetic parameters determined for Group 1 vs. Group 2: t1/2,z = 98 +/- 5 vs. 95 +/- 10 min (mean +/- SEM); V = 3.94 +/- 0.27 vs. 2.98 +/- 25 L/kg; Cl = 28.5 +/- 3.1 vs. 22.3 +/- 1.1 ml kg-1 min-1, respectively. When administered as a continuous intravenous infusion (Group 2), [MID] remained stable at 949 +/- 53 ng/ml for more than 5 hr. The enflurane EC50 was reduced by 55% and the reduction remained stable during the 5 hours of Mid infusion. After a single iv bolus dose or after discontinuation of the continuous infusion, the degree of enflurane EC50 reduction diminished toward the control (i.e., enflurane alone) value as [MID] declined. Mid-azolam's pharmacokinetics and plasma concentration vs. effect relationships have been determined to be consistent under two different experimental conditions.

Anesthesia, General↗
PubMed1988

New perspectives on anesthetic agents.

The practices of anesthesiology are changing to meet the needs of an older and sicker patient population, to adapt to advances in medical technology and operating techniques, and to provide better postoperative conditions for patients and those caring for them. There is a large spectrum of anesthetics and a variety of anesthetic techniques that allow anesthetic onset and recovery to be rapid, vital functions to be maintained within normal limits, and operating conditions to be adapted to the needs of both patients and surgeons. Nevertheless, all anesthetic drugs and techniques have inherent risks as well as benefits, and despite expertise and caution in their use, a satisfactory outcome for the patient cannot be guaranteed.

Analgesia↗
PubMed1988

Use of cardiopulmonary bypass in studies of the circulation.

In summary, CPB provides a complex set of physiological circumstances during which the patient is subjected to severe physiological alterations with surprisingly few adverse sequelae. Our ultimate goal in performing medical research is to provide scientific insights that improve patient care. Results of studies of animal models may not always be applicable to man. Although CPB possesses faults inherent to any experimental model, it nonetheless provides a unique opportunity to study safely and effectively a variety of physiological and pharmacological variables that affect cardiovascular functions in man.

Blood Circulation↗
PubMed1988

Alfentanil plasma concentration v. effect relationships in cardiac surgical patients.

Effects of alfentanil, preceded by lorazepam, on suppression of haemodynamic and somatic responses to noxious stimuli was studied in patients undergoing CABG. Plasma concentration of alfentanil, somatic and haemodynamic responses were measured at loss of consciousness, tracheal intubation, sternotomy and during multiple application of electrocoagulation. Additional alfentanil was administered i.v. to control unwanted responses. Study 1 (six patients): lorazepam 0.08 mg kg-1 by mouth 1-2 h before operation, alfentanil priming infusion (60 micrograms kg-1 min-1 for 10 min) followed by maintenance infusion (4.5 micrograms kg-1 min-1). With mean plasma alfentanil 1178 (SEM 54) ng ml-1, two patients required supplementary alfentanil to suppress somatic motor responses; one patients required nitroglycerin to control an increase in arterial pressure which was unresponsive to additional alfentanil following sternotomy. Study 2 (13 patients): lorazepam 0.04 mg kg-1 by mouth as premedication; one of three maintenance infusion rates of alfentanil: 5.4 (n = 4), 6.6 (n = 5), or 7.8 (n = 4) micrograms kg-1 min-1, each preceded by a proportional priming infusion. With plasma alfentanil 2181 (62) ng ml-1, somatic motor responses requiring additional alfentanil occurred in nine patients; haemodynamic responses in four of seven patients tested could not be controlled by alfentanil. The highest plasma concentration of alfentanil to prevent response to a stimulus other than tracheal intubation was different between the two studies (P less than 0.05). We conclude that alfentanil alone is insufficient to suppress haemodynamic and somatic motor responses to noxious stimulation during CABG and that the role of premedication is significant.

Alfentanil↗
PubMed1988

Nalbuphine antagonism of fentanyl-induced ventilatory depression: a randomized trial.

The authors anesthetized 18 patients with good pulmonary and ventricular function for coronary artery bypass grafting with high doses of fentanyl. When the patients were arousable and their vital signs stable in the intensive care unit, the authors administered nalbuphine or placebo (randomly and double-blinded) until extubation criteria were met, and subsequently gave nalbuphine for analgesia. In one of ten placebo patients, tracheal extubation was accomplished without nalbuphine. This patient then retained CO2 and required nalbuphine; the other nine placebo patients could not be extubated after placebo trials and were given nalbuphine. In all other patients in both groups, tracheal extubation was successful following nalbuphine (median dose 60 micrograms/kg, range 30-180 micrograms/kg). One patient became renarcotized 4 h after tracheal extubation without an increase in plasma fentanyl concentration; he received an additional dose of nalbuphine and recovered without further incident. Nine patients required treatment with vasoactive agents or beta-blockers for hypertension or tachycardia associated with the administration of nalbuphine. Eight of 18 patients were not satisfied with nalbuphine analgesia, and required morphine for relief of their pain. Recurrent elevations of fentanyl concentrations in plasma were observed and appeared to be related to increasing motor activity. Nalbuphine is an effective opioid antagonist after fentanyl anesthesia, but its use is associated with side effects, and analgesia for the post-sternotomy patient may be unsatisfactory unless the dose is carefully titrated to the minimum required to antagonize respiratory depression.

Adult↗
PubMed1988

Comparison of a computer-assisted infusion versus intermittent bolus administration of alfentanil as a supplement to nitrous oxide for lower abdominal surgery.

The anesthesiologist attempts to balance the dose or concentration of an anesthetic against the intensity of noxious stimulation so as to: 1) maintain a satisfactory anesthetic state, 2) minimize side effects and toxicity of the anesthetic, and 3) allow for a rapid recovery from anesthesia. The development of infusion pumps controlled by computers programmed according to pharmacokinetic principles should facilitate the achievement of these objectives for intravenous drugs. To test this hypothesis, the authors compared anesthetic conditions achieved with a computer-controlled infusion to those produced by the traditional method of intermittent intravenous injections. In both cases, the intravenous opiate, alfentanil, was used to supplement nitrous oxide anesthesia, and the dose/dose-rate of alfentanil after the induction dose was guided by the use of precisely defined clinical signs of inadequate anesthesia. One group of ten patients received 10 mg of alfentanil and 66% N2O to induce anesthesia, and was subsequently given 1 or 2 mg iv doses of alfentanil whenever the depth of anesthesia was inadequate. A second group of ten patients had a target alfentanil concentration of 475 ng/ml of plasma established by the computer-controlled infusion, which subsequently raised or lowered the concentration by 50 or 100 ng/ml according to the presence or absence of clinical signs of inadequate anesthesia. Regular measurements of alfentanil concentrations in plasma showed that the computer-assisted infusion produced relatively stable concentrations that closely paralleled those predicted (prediction error of -64 +/- 40 ng/ml [+/- SD] in the range of 150-600 ng/ml). The traditional method of intermittent injections resulted in continuous, rapid fluctuations in alfentanil concentrations. Both methods were successful in controlling the patients' responses to noxious stimuli, but the infusion group had: 1) a lower incidence of responsiveness, 2) greater hemodynamic stability, 3) no patients requiring naloxone for satisfactory ventilation postoperatively, and 4) an incidence of side effects that tended to be lower. The previously reported alfentanil concentration versus anesthetic effect relationships were confirmed.

Adjuvants, Anesthesia↗
PubMed1988

The anesthetic efficacy of midazolam in the enflurane-anesthetized dog.

This study determined the anesthetic efficacy of midazolam (MID) in terms of its ability to reduce enflurane MAC (EMAC). Control EMAC was determined by the tail-clamp method in 15 mongrel dogs. Each animal then received at least three incremental infusion rates of MID from among the following: 0.48, 2.4, 9.6, 19.2, 28.8, 48, or 151.2 micrograms.kg-1.min-1. MAC was determined during each infusion rate following a 1-h observation period, during which time MID concentration in plasma [( MID]) stabilized. [MID] was measured every 15 min beginning 45 min from the start of each new infusion rate. There was a linear relationship between MID infusion rates and the resulting [MID] (r = 0.995). In the range of [MID] from 14 to 14,118 ng/ml, there was a linear relationship between the log [MID] and the percent EMAC reduction. The slope of the line was very shallow, and the [MID] required to reduce EMAC by more than 50% exceeded the [MID] likely to be employed clinically in humans (750 ng/ml). Also, the 73 +/- 4% (mean +/- SEM) EMAC reduction produced by [MID] = 9,763 +/- 1213 ng/ml was not significantly greater than the 60 +/- 3% EMAC reduction achieved by [MID] = 1,464 +/- 293 ng/ml, a finding which suggests a ceiling effect to the anesthetic efficacy of midazolam. The authors conclude that, within the dose range of MID likely to be employed in humans, MID produced a concentration-dependent reduction of enflurane MAC in the dog. In doses above those likely to be employed clinically, a ceiling effect to the anesthetic efficacy of MID may become evident.

Adjuvants, Anesthesia↗
PubMed1987

The enflurane sparing effect of sufentanil in dogs.

There is a ceiling to the reduction of enflurane MAC by fentanyl in the dog. Sufentanil (SUF), a more potent narcotic, may be more efficacious in reducing enflurane MAC. To test this hypothesis, 25 mongrel dogs were studied in three groups. Group 1 (n = 8) received SUF in progressively increasing infusion rates from 0.005 micrograms . kg-1 . min-1 to a maximum of 1.215 micrograms . kg-1 . min-1. MAC was determined at stable SUF concentrations in plasma [SUF] during each infusion rate. Group 2 (n = 10) received SUF at a dose rate (0.007 micrograms . kg-1 . min-1) designed to produce approximately 35% MAC reduction, and MAC determinations were made at regular intervals over a mean infusion time of 7.6 +/- 0.43 h (mean +/- SEM). Group 3 (n = 7) received 1.215 micrograms . kg-1 . min-1 and were studied as in group 2 over an infusion time of 6.7 +/- 0.42 h. In group 1, the highest infusion rate (1.215 micrograms . kg-1 . min-1) produced [SUF] = 48 ng/ml and reduced MAC by 71 +/- 6%. This was not statistically different from the reduction which occurred at [SUF] = 0.92 ng/ml (57 +/- 7%; infusion rate 0.015 micrograms . kg-1 . min-1; P = 0.21). In group 2, the degree of MAC reduction achieved by stable [SUF] (0.54 +/- 0.08 ng/ml) declined over time (MAC reduction at start = 34 +/- 2% versus 18 +/- 4.0% at the end of the infusion; P = 0.001), suggesting the development of tolerance.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

The enflurane-sparing effect of alfentanil in dogs.

Some investigators believe that the dog is less sensitive than are humans to the anesthetic/analgesic actions of opioids. The alfentanil plasma concentration [ALF] vs anesthetic effect relationship has been determined for humans undergoing surgery. This study was designed to determine the [ALF] vs anesthetic relationship for alfentanil in the enflurane-anesthetized dog and thereby to provide data by which the [ALF] vs anesthetic effect relationships in the dog and in humans could be compared. Mongrel dogs (n = 10) were anesthetized with enflurane, and enflurane MAC (EMAC) was determined in each dog. After this, each dog received at least three incremental infusions of alfentanil using infusion rates of 0.625, 1.6, 8, 32, or 80 micrograms.kg-1.min-1. EMAC and [ALF] were determined during each infusion rate. There was a linear increase in [ALF] produced by incremental infusions of alfentanil (r = 0.999). Administration of alfentanil produced a dose-dependent reduction of EMAC up to a maximum of 72.5 +/- 3.7% (mean +/- SEM) at 32 micrograms.kg-1.min-1 ([ALF] = 960 +/- 86 ng/ml); a ceiling effect was evident. The degree of EMAC reduction (69%) produced by an infusion rate of 8 micrograms.kg-1.min-1 ([ALF] = 223 +/- 13 ng/ml) was not statistically different from the EMAC reductions produced by infusion rates of 32 (73% reduction at [ALF] = 960 +/- 86 ng/ml) or 80 micrograms.kg-1.min-1 (70% reduction at [ALF] = 2613 +/- 247 ng/ml) (P greater than 0.05). The relative potency of alfentanil was one-seventh to one-tenth that of fentanyl studied under identical conditions.(ABSTRACT TRUNCATED AT 250 WORDS)

Adjuvants, Anesthesia↗
PubMed1987

Dezocine-MAC reduction and evidence for myocardial depression in the presence of enflurane.

The effect of dezocine, an agonist-antagonist opioid analgesic, on enflurane MAC (EMAC) was measured in dogs and, in a separate study, the hemodynamic effects of IV bolus doses of dezocine in the presence of a stable end-tidal enflurane concentration were measured. Study 1 (n = 8)--EMAC Reduction: Dezocine reduced EMAC in a dose-dependent fashion by a maximum of 58 +/- 3% (mean +/- SEM) after injection of 20 mg/kg. Cardiac toxicity prevented administration of higher doses. Study 2--Hemodynamics: Group 1 (n = 7) received dezocine 0.2, 1.5, 5, and 20 mg/kg IV each as a bolus over 30 sec. Group 2 (n = 5) was studied in exactly the same manner except that instead of dezocine, each dog received drug carrier solution alone (carrier). Significant hemodynamic differences between carrier and drug groups were observed only at the 20 mg/kg dose level, which produced death in one dog and a decrease in mean aortic pressure to 39 +/- 5% of baseline, in cardiac output to 60 +/- 9% of baseline, and in stroke volume to 69 +/- 9% of baseline in the remaining dogs. It is concluded that dezocine produces a dose-dependent reduction in EMAC limited by cardiovascular toxicity. This toxicity appears to be related to direct myocardial depression by high doses of dezocine in the presence of enflurane.

Analgesics↗
PubMed1986

Plasma concentrations of alfentanil required to supplement nitrous oxide anesthesia for general surgery.

To design an efficient infusion regimen from pharmacokinetic data, it is necessary to know the alfentanil plasma concentrations required for satisfactory anesthesia. In 37 patients about to undergo lower abdominal gynecologic, upper abdominal, or breast surgery, anesthesia was induced with alfentanil 150 micrograms/kg iv and 66% N2O in oxygen. Thereafter, N2O anesthesia was supplemented with a continuous infusion of alfentanil that was varied between 25 and 150 micrograms X kg-1 X h-1, as indicated by the patient's responses to surgical stimulation. Small bolus doses of alfentanil 7 or 14 micrograms/kg were administered and the infusion rate increased to suppress precisely defined somatic, autonomic, and hemodynamic responses. Arterial plasma concentrations of alfentanil were measured during the operation when the patient did and did not respond to noxious stimulation. Logistic regression was used to determine plasma concentration-effect curves for different stimuli. Plasma alfentanil concentrations required along with 66% N2O to obtain responses to single episodes of stimulation in 50% of the 37 patients (Cp50 +/- SE) were: 475 +/- 28 ng/ml for tracheal intubation, 279 +/- 20 ng/ml for skin incision, and 150 +/- 23 ng/ml for skin closure. Between skin incision and closure, multiple determinations of response/no response were made for each patient and an individual Cp50 was estimated. The Cp50 (mean +/- SD) for the three surgical procedures were: breast, 270 +/- 63 ng/ml (n = 12); lower abdominal, 309 +/- 44 ng/ml (n = 14); and upper abdominal, 412 +/- 135 ng/ml (n = 11). The Cp50 for satisfactory spontaneous ventilation after the discontinuation of N2O was 223 +/- 13 ng/ml. These data demonstrate that different perioperative stimuli require different alfentanil concentrations to suppress undesirable responses. Thus, the alfentanil infusion rate should be varied according to the patient's responsiveness to stimulation in order to maintain satisfactory anesthetic and operative conditions and to provide rapid recovery of consciousness and spontaneous ventilation.

Adult↗
PubMed1986

Esmolol attenuates hemodynamic responses during fentanyl-pancuronium anesthesia for aortocoronary bypass surgery.

We evaluated the effects of esmolol, a short acting (t1/2 beta = 9 min) beta-blocker on hemodynamics during noxious stimulation associated with aortocoronary bypass surgery. Group E (n = 10) and P (n = 10) patients had their morning dose of beta- or calcium blockers withheld except for nifedipine, and were given infusions of esmolol (E) or placebo (P) beginning prior to anesthetic induction and continuing until mediastinal dissection. Group S (n = 10) patients received their usual medication the morning of surgery and received neither esmolol nor placebo. All patients received fentanyl infusions for anesthesia and pancuronium for relaxation. Esmolol patients had no changes in heart rate throughout the study. In contrast, significant increases in heart rate occurred during induction, intubation, and surgical stimulation in Groups P and S. Esmolol patients had a statistically significant but transient increase in pulmonary capillary wedge pressure (PCWP) after intubation, which did not require treatment. There were no significant changes in PCWP in Group S and a decrease in PCWP in Group P patients. We conclude that esmolol was effective in attenuating potentially deleterious responses to noxious stimulation during fentanyl-pancuronium anesthesia.

Adult↗
PubMed1985

High-dose fentanyl for rapid induction of anaesthesia in patients with coronary artery disease.

Nine premedicated patients, chronically maintained on beta-adrenergic blocking agents and demonstrating good ventricular function without significant valvular or left main coronary artery disease, were investigated to determine their haemodynamic responses to rapid induction of anaesthesia and tracheal intubation during elective coronary artery bypass surgery. Fentanyl 50 micrograms X kg-1 and pancuronium 0.15 mg X kg-1 were administered intravenously over 20 seconds followed by tracheal intubation 90 seconds thereafter. The rapid sequence of anaesthetic induction and tracheal intubation was well tolerated by all patients. Though statistically significant changes were detected in heart rate, pulmonary capillary wedge pressure and systemic vascular resistance, these changes were small and not considered clinically significant and no signs of ischaemia were detected on the ECG. The present study demonstrates that high-dose fentanyl is capable of inducing anaesthesia rapidly and protecting against the haemodynamic changes associated with tracheal intubation.

Adrenergic beta-Antagonists↗
PubMed1985

An evaluation of the accuracy of pharmacokinetic data for the computer assisted infusion of alfentanil.

The accuracy of using average alfentanil pharmacokinetic data in a computer assisted infusion pump (TIAC) to predict alfentanil plasma concentrations was tested in 35 patients (divided into three groups) receiving alfentanil and nitrous oxide in oxygen anaesthesia for lower and upper abdominal surgery. By frequently measuring the arterial plasma concentration, it was possible to determine the average prediction error for individual patients and for groups of patients. For the groups, there were no significant systematic over- or underpredictions of the alfentanil plasma concentrations (bias). However, there existed a moderate degree of variability (imprecision) within the groups, caused by deviations of measured and predicted plasma concentrations in the individual patients within each group. As a result, prediction errors of 22.2-32.5% can be expected with the average pharmacokinetic data used in this study to drive TIAC. It was concluded that, as a result of the moderate degree of imprecision, it is unwise to rely totally on the absolute values of alfentanil plasma concentrations predicted by a computer-regulated infusion pump such as TIAC. However, such devices can be used to attain rapidly a relatively stable plasma concentration that can be adjusted (titrated) to the requirements of an individual patient during anaesthesia.

Adjuvants, Anesthesia↗