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Biomedical subjects

C C Hug

Publications and source records attributed to C C Hug.

At least 73 records · Page 4Linked to original sources
PubMed1984

Rectal and intravenous propranolol infusion to steady state: kinetics and beta-receptor blockade.

The effects of intravenous propranolol infusion for 24 hr was compared with those of zero-order rectal administration by an osmotic delivery system in six healthy subjects. In plasma and urine, levels of propranolol, 4-OH-propranolol (4-OH-P), and conjugates were determined just before and at 6 hr and at 20 hr during drug administration. With the rectally applied osmotic delivery system providing zero-order release, fairly constant steady-state levels of propranolol in plasma were produced within 12 to 15 hr (four to five times elimination t1/2). The mean steady-state levels were 25 ng/ml after 1.1 micrograms/min/kg rectally and 60 ng/ml after 0.8 micrograms/min/kg IV. The mean rectal systemic availability was 33%; the elimination t1/2s for the two routes did not differ. The results of analysis of plasma for metabolites indicate that after rectal propranolol different metabolic pathways are followed and that there is partial avoidance of first-pass elimination. The isoproterenol challenge resulted in a reproducible assessment of beta-receptor blockade that was closely related to the propranolol concentration in plasma in all subjects and for both routes of administration. With rate-controlled release of propranolol from an osmotic delivery device, the rectal route provides an alternative to intravenous infusion to achieve constant steady-state propranolol concentrations. This may be useful for research purposes or during the perioperative period in surgical patients.

Adult↗
PubMed1984

High-dose hydromorphone (Dilaudid) for coronary artery bypass surgery.

The hemodynamic effects of high-dose hydromorphone hydrochloride (H), 1.25 mg/kg, were investigated in 10 patients with normal ventricular function undergoing coronary artery bypass graft (CABG) surgery. One patient with unstable angina was excluded from the study because of hypotension and facial flushing after a 6-mg test dose of H. Nine patients showed no significant change in heart rate (HR), mean arterial pressure (MAP), cardiac index (CI), left ventricular stroke work index (LVSWI), systemic vascular resistance (SVR), pulmonary capillary wedge pressure (PCWP), or coronary perfusion pressure (CPP) after H; central venous pressure (CVP) increased significantly (P less than 0.05). Loss of consciousness did not occur reliably after H. The addition of 50% N2O to H produced significant decreases in CI and LVSWI (P less than 0.05). Hemodynamic responses to tracheal intubation, skin incision, and sternotomy included depression of CI, elevation of SVR, and increased MAP (P less than 0.05). Vasodilators were required in eight patients before aortic cannulation and after extracorporeal circulation. Mean time to awakening was 7.6 hr after the full dose of H, and extubation was performed the morning after surgery (21 hr after H) according to our usual practice. We conclude that very large doses of H (equivalent in analgesic terms to 10 mg/kg of morphine sulfate) are well tolerated by most patients undergoing CABG surgery, but unconsciousness and complete suppression of sympathetic responses require supplementation of H with additional anesthetic agents or vasodilators.

Anesthesia↗
PubMed1984

Absence of seizures during induction of anesthesia with high-dose fentanyl.

Anesthesia was induced in six patients scheduled for elective aortocoronary bypass (ACB) surgery with intravenous fentanyl, either 50 (n = 2) or 150 micrograms/kg (n = 4) over 20 or 60 sec, respectively. Patients had been given their usual antianginal medications before surgery and were premedicated with morphine sulfate. Arterial plasma fentanyl levels were measured repetitively at frequent intervals, and eight leads of the cortical electroencephalogram (EEG) were recorded continuously. Peak plasma fentanyl concentrations exceeded 1750 ng/ml at the end of the injection of 150 micrograms/kg and then decreased by more than 75% within 3 min. In an additional two patients, incremental doses of fentanyl (25, 25, 50, 50 micrograms/kg; total 150 micrograms/Kg) maintained fentanyl concentrations between 30 and 650 ng/ml for the entire 15 min of the study. In all cases, diffuse slow-wave EEG activity, characteristic of fentanyl anesthesia, was seen. Motor activity, including wrist flexion and ocular movements, was observed during the onset of fentanyl-induced truncal rigidity, but no seizure-like activity was found in the EEG.

Aged↗
PubMed1983

Non-cardiac surgery in patients with prior myocardial revascularization.

Patients who had undergone aorto-coronary bypass grafts (ACBG) were assessed for the incidence of cardiac complications in the postoperative period following subsequent non-cardiac surgery. One hundred and twenty-one patients had 13 complications (11 per cent). A significantly higher risk of cardiac complications (27 per cent) was found in patients undergoing non-cardiac procedures in the first month after ACBG. This remained higher (17 per cent) until the sixth month following ACBG. Significant factors which increased the risk of cardiac complications in the postoperative period included preoperative congestive heart failure (33 per cent), cardiac risk index score classification of III or IV (37 per cent), surgery on major vessels, and surgery necessitated because of a complication of the ACBG itself (17 per cent). No correlation was found between cardiac complication rates and recurrent angina, hypertension, the use of beta-blockers or digoxin, or anaesthetic technique. It is suggested that all but emergency surgery should be postponed in the first month following ACBG, and elective surgery be delayed for up to six months.

Adult↗
PubMed1983

Hemodynamic interactions of verapamil and isoflurane.

The hemodynamic interactions of verapamil and isoflurane were studied in eight dogs. Left ventricular function was analyzed using a right heart bypass preparation to permit rigid hemodynamic control. Hemodynamic studies were performed at 0.7, 1.05, and 1.40% isoflurane before and during the maintenance of two stable levels of verapamil, administered intravenously by combining a bolus dose (0.2 mg X kg-1) with an infusion (3.0 and 6.0 micrograms X kg-1 X min-1). Isoflurane produced a concentration-dependent depression of left ventricular function as indicated by dP/dt max, per cent systolic shortening, and left ventricular function curves. This depression was enhanced in a dose-plasma concentration-dependent manner by verapamil and was reversed by calcium chloride. Isoflurane alone and the combination of verapamil and isoflurane decreased systemic vascular resistance in a dose-dependent fashion that was antagonized partially by calcium chloride. Therefore, verapamil can enhance the hemodynamic effects of isoflurane in a dose-related manner that needs to be considered when both drugs are administered together.

Animals↗
PubMed1983

Dose-independent pharmacokinetics of fentanyl.

Fentanyl is used as an analgesic in small doses (1-2 micrograms X kg-1) and as an anesthetic in very large doses (greater than 150 micrograms X kg-1). It has been demonstrated that the effects of fentanyl correlate with its concentrations in plasma. It is important, therefore, to know whether or not the pharmacokinetics of fentanyl vary with dose size in order to predict the plasma concentrations and effects produced by various dosage regiments. The authors studied the pharmacokinetics of fentanyl in dogs. 3H-fentanyl (2.5-640 micrograms X kg-1) was injected intravenously in dogs anesthetized at a stable level with enflurane-O2. Arterial plasma and urine were analyzed for unchanged 3H-fentanyl. Kinetic indices were derived by nonlinear least-squares analysis of log concentration of fentanyl in plasma (ng X ml-1) versus time after a bolus injection. The terminal elimination half-time (t 1/2 beta = 211 min), the apparent volume of distribution (9.5 l X kg-1), the volume of the central compartment (1.14 l X kg-1), and the clearance (37 ml X kg-1 X min-1) of fentanyl were independent of dose over the 6.4-640 micrograms X kg-1 dose range. The distribution volume and distribution half-times were lower for the 2.5 micrograms X kg-1 than for some of the larger doses; this was attributed to differences in experimental conditions. The authors conclude that the pharmacokinetics of fentanyl are dose independent certainly over the 6.4-640 micrograms X kg-1 dose range. There is no evidence of saturation of biotransformation or tissue uptake mechanisms for doses in the range of 2.5 to 640 micrograms X kg-1.

Animals↗
PubMed1983

Variable rate infusion of alfentanil as a supplement to nitrous oxide anesthesia for general surgery.

In this study we attempted to define the minimal dosage of alfentanil (AF) needed in combination with nitrous oxide to provide satisfactory anesthetic conditions for lower abdominal gynecologic surgery. General anesthesia was induced in 12 women with AF (150 micrograms X kg-1) and 66% N2O in O2. An infusion of AF was started immediately after the AF induction dose and was varied between 25-150 micrograms X kg-1 X hr-1 as indicated by the patient's responses to stimulation during operations lasting 208 +/- 22 (SEM) min. Small bolus doses of AF (7 micrograms X kg-1) were administered to rapidly suppress precisely defined somatic, hemodynamic, and other sympathetic responses to stimulation. With one exception, all responses in all patients were controlled rapidly by increments of AF. The mean dosages of AF needed during different stages of surgery are reported. The AF infusion was stopped 16.2 +/- 1.2 min before discontinuing N2O. Recovery of consciousness along with satisfactory spontaneous ventilation occurred promptly after completion of the operation (4.0 +/- 0.5 min after N2O; 20.3 +/- 1.4 min after stopping AF infusion). This study demonstrates the feasibility of maintaining general anesthesia with N2O and a continuous AF infusion at a rate varied according to the patient's responses and allowing for prompt recovery of consciousness and satisfactory spontaneous ventilation at the conclusion of operations lasting as long as 5 hr.

Adult↗
PubMed1983

Plasma concentrations of alfentanil required to supplement nitrous oxide anaesthesia for lower abdominal surgery.

In 15 patients about to undergo lower abdominal surgery, anaesthesia was induced with alfentanil 150 micrograms kg-1 i.v. and 66% nitrous oxide in oxygen. Thereafter, nitrous oxide anaesthesia was supplemented with a continuous infusion of alfentanil at a rate which varied between 25 and 150 micrograms kg-1, as indicated by the patient's responses to the stimulation of surgery. Small bolus doses of alfentanil 7 micrograms kg-1 were administered to suppress precisely defined somatic, haemodynamic and other responses to stimulation. With one exception, all responses were rapidly controlled by increments of alfentanil. By measuring the arterial plasma concentrations of alfentanil at times with and without a response, we were able to estimate the alfentanil concentrations required (with nitrous oxide) to suppress responses to different stimuli during surgery. The results demonstrate the feasibility of continuous infusion of alfentanil in anaesthesia.

Abdomen↗
PubMed1982

Gas chromatographic analysis of ketamine and norketamine in plasma and urine: nitrogen-sensitive detection.

A sensitive gas chromatographic method for quantitative analysis of ketamine and norketamine in human and animal biological fluids is described. The nitrogen-sensitive detection procedure used is more stable than electron-capture detection and reduced analysis time. The method used bromo-ketamine as an internal standard for quantitation and is linear from 10-25,000 ng/ml. No interferences were shown with drugs commonly associated with cardiac surgery with cardiopulmonary by-pass. This assay is sensitive, specific, using either native or derivatized drugs and can be used for routine analysis of ketamine and norketamine in plasma or urine.

Adult↗
PubMed1982

The anesthetic potency of fentanyl in terms of its reduction of enflurane MAC.

Infusion rates for fentanyl were calculated to produce stable plasma concentrations at which the ability of fentanyl to reduce enflurane MAC could be studied utilizing the tail clamp method and measurement of end-tidal enflurane. Following the determination of control enflurane MAC in each animal, an infusion of fentanyl was begun. Group 1 received continuous successive infusion rates of 0.05, 0.1, and 0.2 micrograms . kg-1 . min-1 with respective loading doses (given over 20 min) of 15, 15, and 30 micrograms/kg; Group 2 received infusions of 0.2, 0.8, and 3.2 micrograms . kg-1 . min-1 with loading doses of 30, 90, and 270 micrograms/kg, respectively. Group 3 was studied in the same manner except that fentanyl was omitted from the infusion solution. Enflurane MAC was determined at each infusion level and blood samples were analyzed for the concentration of fentanyl. Fentanyl concentrations in plasma were proportional to the infusion rate. Enflurane MAC was decreased significantly in proportion to fentanyl plasma concentrations up to 30 ng/ml where a reduction of MAC by 65% was evident. A threefold higher concentration produced a minimal further reduction. In Group 3 dogs, no change in enflurane MAC was seen. It was concluded that predictable, stable levels of fentanyl in plasma can be achieved, that there is a close relationship between the concentration of fentanyl in plasma and its enflurane sparing effect, and that there is a ceiling to this concentration-response relationship.

Anesthesia, General↗
PubMed1982

The enflurane sparing effect of morphine, butorphanol, and nalbuphine.

The potencies of morphine and of the narcotic analgesic agonist-antagonists butorphanol and nalbuphine in terms of their ability to decrease enflurane MAC were studied. Following the determination of control MAC for enflurane in each dog, an intravenous bolus dose of either butorphanol tartrate, nalbuphine hydrochloride, morphine, or placebo was administered and enflurane MAC was redetermined. A higher dose of the same drug was then administered and enflurane MAC was redetermined up to a total of four doses in each animal. The successive doses for morphine and nalbuphine were 0.5, 1.5, 5.0, and 20.0 mg/kg; for butorphanol, 0.1, 0.3, 1.0, and 4.0 mg/kg; lactated Ringer's solution was used as a placebo. Both butorphanol and nalbuphine produced significant reductions of enflurane MAC (11 and 8%, respectively) at their lowest doses. No further reductions were produced by three- to forty-fold larger doses of either agonist-antagonist. Morphine produced a 17% reduction of enflurane MAC at the lowest dose with progressive decreases of enflurane MAC up to 63% at a dose of 5 mg/kg morphine. A fourfold increase in the morphine dose did not further decrease MAC. No change in enflurane MAC occurred in the animals given placebo. It was concluded that there is a "ceiling" to the potency of butorphanol and nalbuphine as anesthetic supplements. There is also a limit to the anesthetic sparing effect of morphine, but it is considerably greater than that of the agonist-antagonist narcotic analgesics.

Anesthetics↗
PubMed1981

Pharmacokinetics of intravenous morphine in patients anesthetized with enflurane-nitrous oxide.

Morphine is used as an anesthetic supplement. Its disposition in surgical patients under enflurane-nitrous oxide anesthesia has not been determined. Available data on morphine concentrations in plasma after equivalent intravenous doses are conflicting, possibly as a result of varying degrees of specificity of the analytical methods for the unchanged, pharmacologically active form of the drug. This study determined the pharmacokinetics of morphine (0.05, 0.1, 0.14, or 0.2 mg/kg) injected intravenously in 10 surgical patients anesthetized with enflurane-N2O-O2. Arterial plasma was analyzed for unchanged morphine and conjugated morphine. Specificity of the analytical procedure for unchanged morphine was achieved by the combination of solvent extraction and radioimmunoassay techniques. Kinetic indices were derived by nonlinear least-squares analysis of log concentration (ng/ml) vs. time relationships. Morphine disposition was independent of dose in this fourfold range and was best described by a three-compartment model with a mean elimination half-time (t1/2 beta) of 104 +/- 5 min. The apparent volumes of distribution (Vd) and of the central compartment (V1) were 3.4 +/- 0.2 and 0.13 +/- 0.02 l/kg, respectively, while the clearance (ClB) was 23 +/- 1 ml x min-1 x kg-1. Extraction of morphine by the liver appeared to be complete. Conjugated morphine was eliminated from plasma with a t1/2 beta of 169 +/- 15 min. The ultimate elimination of morphine from the body was dependent upon its uptake from slowly perfused peripheral tissues, K10 greater than k31(P less than .001).

Adolescent↗
PubMed1981

Hemodynamic changes during fentanyl--oxygen anesthesia for aortocoronary bypass operation.

Fentanyl in doses of 50-60 microgram/kg has been reported to produce anesthesia with remarkable hemodynamic stability in patients with coronary artery disease (CAD). Because the authors had observed hypertension and tachycardia in response to noxious stimulation during aortocoronary bypass (ACB) operations in patients so anesthetized, they studied the hemodynamic changes and anesthetic conditions produced by fentanyl/O2/relaxant anesthesia in patients undergoing elective ACB. Twelve patients with left ventricular (LV) ejection fractions greater than 0.4 were maintained on propranolol until 10 hours before operation and were premedicated with fentanyl, diazepam, and scopolamine. Cannulae were inserted before the study commenced for measurement of intravascular pressures, arterial blood gases, and thermodilution cardiac output. The patients breathed 100 per cent oxygen throughout the study. Controlled ventilation aided by succinylcholine to reduce truncal rigidity maintained PaCO2 at 30-45 torr. Measurements were made after each of the following: breathing oxygen (control), 10 microgram/kg fentanyl, 50 microgram/kg fentanyl, and 0.1 mg/kg pancuronium, tracheal intubation, skin incision, and sternotomy. Fentanyl alone produced no significant hemodynamic changes. Fentanyl and pancuronium in combination produced increased heart rate and reduced stroke volume. Significant and progressively greater increases in mean arterial pressure and systemic vascular resistance followed intubation, skin incision, and sternotomy. Chest rigidity occurred in every patient at a lower fentanyl dose than did unresponsiveness. While fentanyl, 62.4 +/- 2.9 microgram/kg (SE), produced minor hemodynamic changes, it failed to block hemodynamic responses to noxious stimulation. Such changes resulted in increased cardiac work, and could have affected myocardial oxygen balance unfavorably. In eight of the 12 patients, following the last set of measurements, supplementary anesthetic agents were required to maintain hemodynamic stability during the surgical procedure. The authors suggest that this fentanyl/O2/relaxant technique should be modified for patients with severe CAD and reasonably good LV function.

Blood Pressure↗
PubMed1981

Tissue redistribution of fentanyl and termination of its effects in rats.

The kinetics of fentanyl elimination from plasma suggest its rapid and extensive uptake by tissues. The authors determined the relationships between tissue and plasma concentrations of fentanyl. Six rats injected iv with 3H-fentanyl citrate (50 micrograms/kg) were sacrificed at each of the following times: 1.5, 5, 15, 30, 60, 120, and 240 min after injection. Tissues were analyzed for unchanged 3H-fentanyl citrate and for total 3H-radioactivity. Fentanyl effects were evident 10 s after injection; recovery began at 5 min and was complete within 60 min. Fentanyl concentrations in brain, heart, and lung equilibrated with that in plasma before 1.5 min and declined at the same rate (t 1/2 alpha = 8 min, t 1/2 beta = 45 min). Fentanyl uptake by muscle and fat was slower and equilibration with plasma occurred by 120 min. Muscle accumulated 56 per cent of the dose within 5 min by which time brain fentanyl levels had declined by 90 per cent. Only 6 per cent of the dose was in fat at 5 min but this increased to a maximum of 17 per cent at 30 min. Fentanyl was extensively metabolized; metabolites represented 25 per cent of body 3H-radioactivity at 15 min, and 80 per cent at 4 h. The authors conclude that the short duration of fentanyl effect is due to its rapid redistribution from sites of action in the brain to sites of storage (muscle and fat) and biotransformation (liver). The elimination of fentanyl from the body is governed by its reuptake from storage sites and its metabolism in the liver. Most of the dose is ultimately excreted in the form of fentanyl metabolites in urine.

Adipose Tissue↗