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Biomedical subjects

C C Hug

Publications and source records attributed to C C Hug.

At least 19 recordsLinked to original sources
PubMed1992

Opioids: clinical use as anesthetic agents.

Opioids (narcotic analgesics) are widely used in the practice of anesthesia for preanesthetic medication, systemic and spinal analgesia, supplementation of general anesthetic agents, and as primary anesthetics. The last use is particularly widespread for major surgical operations, especially those involving patients with cardiovascular disease. The use of opioids in anesthetic doses is based on the absence of cardiac depression by the opioids. As with all anesthetic drugs, the opioids have limitations and side effects, but for the most part, these are easily managed on the basis of knowledge of their pharmacology. The key to their efficient use is careful titration of dose according to the individual patient's responses to the drug as well as to noxious stimulation. Although there is a very wide margin of safety, allowing administration of enormous doses intraoperatively when the patient's ventilation is supported mechanically, the disadvantage of using doses far in excess of the individual patient's need is a prolonged recovery from anesthesia with the risk of postoperative ventilatory depression. Titration of the dose can be facilitated by computer-controlled infusion pumps with the benefit that the recovery time from anesthetic doses can be appropriate for the individual patient and surgical procedure, and postoperative analgesia can be continued by patient-controlled analgesia, which is another example of computer-controlled opioid infusion. Although specific opioid antagonists are available, their use to antagonize residual anesthetic effects is potentially hazardous.

Anesthesia↗
PubMed1992

Pharmacodynamics of pentamorphone during coronary artery bypass grafting in humans.

Pentamorphone is a new, highly potent opioid reported to have minimal cardiovascular effects in humans and a high therapeutic index in animals. Pentamorphone was injected intravenously (IV) as the sole anesthetic in 10 patients with left ventricular ejection fractions greater than 0.35 who were undergoing elective coronary artery bypass grafting (CABG). After premedication with lorazepam, 40 micrograms/kg, and establishment of hemodynamic monitoring, pentamorphone was infused at a rate of 2 micrograms/kg/min until unconsciousness occurred (5.1 +/- 1.6 micrograms/kg). Anesthetic induction was accompanied by an average 30% decrease in systolic, diastolic, and mean arterial pressure (MAP), a 19% decrease in heart rate (HR), but no change in cardiac output (CO) or pulmonary artery occlusion pressure. Five patients had a MAP less than 60 mm Hg after induction. Following incision, blood pressure, pulmonary artery occlusion pressure, and CO were unchanged from baseline but HR remained significantly lower. Despite additional pentamorphone (total dose 9.6 +/- 1.8 micrograms/kg), 6 patients required thiopental and/or enflurane to control hypertension intraoperatively. When pentamorphone is used as the sole IV anesthetic in lorazepam-premedicated patients with normal or mildly impaired ventricular function, there is a high incidence of hypotension during induction, and poor control of hemodynamic responses to stimulation. Pentamorphone, 10 micrograms/kg, does not seem to offer any significant advantage over opioids currently used for anesthesia in patients undergoing CABG.

Aged↗
PubMed1992

Development of the knowledge-based standard for the written certification examination of the American Board of Anesthesiology.

In 1988 and 1989, the American Board of Anesthesiology (ABA) developed a knowledge-based standard for its written certification examination. In brief, 13 "judges" developed a construct of a "borderline candidate," i.e., a candidate who was neither ideal nor clearly failing but rather had sufficient knowledge to just pass. In 1989, this construct was applied to 90 questions from the 1989 ABA examination to estimate candidate's score on that subset. When extended to the entire examination, the use of the construct resulted in a knowledge-based standard of 57% correct. (The 1988 exercise, also using the construct of a borderline candidate but with a totally different subset of questions, produced an identical standard). This standard resulted in higher success rates among the actual examinees taking the ABA examination (84% in 1989 and 90% in 1990) than had the normative standard used previously (80%). The authors suggest that the process they describe permits development of a reproducible criterion for success that is based entirely on mastery of a relevant body of knowledge rather than on normative considerations.

Anesthesiology↗
PubMed1991

The pharmacokinetics and pharmacodynamics of ketamine in dogs anesthetized with enflurane.

The plasma concentration vs. anesthetic effect relationships for ketamine are not well known. It is desirable to establish stable and predictable drug concentrations in plasma (and brain) in order to define such relationships. As a prelude to pharmacodynamic studies, we investigated ketamine pharmacokinetics in eight dogs anesthetized with enflurane and correlated ketamine concentration in plasma (KET) with its ability to reduce the enflurane concentration required for anesthesia (enflurane EC50: MAC--the end-tidal concentration at which half the dogs moved in response to clamping of the tail and half did not move). Four dogs (Group 1) received ketamine 10 mg/kg iv over 30 sec. Blood for determination of KET was collected repeatedly over the 5-h period following injection. Based on the pharmacokinetic parameters determined for Group 1, four dogs in Group 2 received ketamine as a continuous infusion of 300 micrograms.kg-1.min-1 for 5 hr accompanied by an initial loading dose (26 mg/kg administered over 20 min) designed to produce a stable KET of 20 micrograms/ml of plasma. Enflurane MAC and KET were determined regularly during the infusion and for 5 hr after discontinuation of the infusion. There were no significant differences in the following pharmacokinetic parameters determined for Group 1 vs. Group 2: t1/2 beta = 122 +/- 9 vs. 141 +/- 40 min (mean +/- SD) and CL = 18.1 +/- 5.9 vs. 13.9 +/- 2.5 ml.kg-1.min-1, respectively. When administered as a continuous infusion (Group 2), KET remained relatively stable at 22.1 +/- 4.6 micrograms/ml for 5 hr. The degree of MAC reduction remained relatively stable at 73% during the continuous infusion. Finally, the enflurane MAC reduction vs. KET was established over a wide range of plasma concentrations in 4 additional dogs (Group 3). This study determined that the pharmacokinetics of ketamine were consistent under two different experimental conditions and demonstrated the relationship between plasma concentration and anesthetic effect in the dog.

Anesthesia↗
PubMed1991

Less than additive antinociceptive interaction between midazolam and fentanyl in enflurane-anesthetized dogs.

The anesthetic interactions of midazolam and fentanyl were determined in terms of enflurane MAC reduction in dogs. In part 1, 8 animals received an intravenous (iv) loading dose of fentanyl followed by a constant infusion at 0.05 micrograms.kg-1.min-1 to produce a stable enflurane MAC reduction of approximately 20%. Midazolam was then administered in a series of three incremental loading doses and infusions (2.4, 9.6, and 28.8 micrograms.kg-1.min-1 previously determined to produce enflurane MAC reductions of approximately 30, 45, and 60%, respectively. Enflurane MAC was determined for each infusion. Then fentanyl was discontinued; naloxone 1 mg/kg was administered; and enflurane MAC was determined. In part 2, six dogs received a loading dose and a continuous infusion of fentanyl (0.2 micrograms.kg-1.min-1) designed to produce a stable enflurane MAC reduction of approximately 40%. A series of two incremental loading doses and infusions of midazolam (2.4 and 28.8 micrograms.kg-1.min-1) were added, and MAC determinations were repeated at each infusion rate. Then midazolam was discontinued; flumazenil (RO 15-1788) 1.5 mg/kg was administered; and enflurane MAC was determined. The fentanyl concentrations in plasma remained stable at 1.0 +/- 0.3 ng/ml (mean +/- standard deviation [SD], part 1) and 3.1 +/- 0.5 ng/ml (part 2) throughout the study and, in the absence of midazolam, reduced enflurane MAC by 28 +/- 11 and 44 +/- 5%, respectively. The addition of midazolam produced significant further reductions in enflurane MAC, but the reductions were less than those predicted on the basis of an additive interaction. Naloxone returned enflurane MAC reduction to that expected for midazolam alone (part 1).(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia, Inhalation↗
PubMed1991

Pharmacokinetics of amrinone during cardiac surgery.

Amrinone is a nonglycosidic noncatecholamine with both vasodilator and positive inotropic effects that may be administered to patients undergoing cardiac surgery. As an initial step toward elucidating the optimal dosage of amrinone for cardiac surgical patients we studied the pharmacokinetics of amrinone during and after cardiac surgery requiring cardiopulmonary bypass. The study population comprised 35 adult patients, each receiving a single dose of amrinone (0.75, 1.5, 2.0, or 2.5 mg/kg) administered into the venous reservoir near the end of cardiopulmonary bypass. Additionally, 15 of the 35 patients also received intravenous infusions of either 5 or 10 micrograms.kg-1.min-1. Arterial blood was sampled over the next 22 h, and plasma concentrations of amrinone were determined by high-performance liquid chromatography. Protein binding of amrinone, assayed by equilibrium dialysis, was 21.6 +/- 2.5%. The decay of amrinone concentrations in plasma over time was fit to a biexponential equation by nonlinear least-squares regression. The manufacturer's recommended dose of 0.75 mg/kg followed by an infusion of 10 micrograms.kg-1.min-1 was inadequate to maintain the plasma concentration within the therapeutic range based on the pharmacodynamics of amrinone in patients with chronic congestive heart failure. This was due to significant redistribution of amrinone in the body after the loading dose. To maintain a therapeutic plasma concentration of 1.5-2.0 micrograms/ml, a larger loading dose or a supplemental loading dose as well as a continuous infusion is required.

Amrinone↗
PubMed1991

Assessing the adequacy of fentanyl anesthesia: plasma concentrations and lower esophageal contractility.

Assessing the adequacy of anesthesia in the paralyzed patient is usually based on sympathetic and hemodynamic responses to noxious stimulation. Absence of such responses does not guarantee adequate anesthesia. A device monitoring the amplitude of provoked lower esophageal, contractility (PLEC) and the rate of spontaneous lower esophageal contractility (SLEC) has been developed as a potential monitor of the adequacy of anesthesia. This study determined the reliability of this device for monitoring anesthetic depth in 20 patients receiving fentanyl infusions who were undergoing coronary artery surgery and who were hemodynamically stable in the preoperative period. Premedication included midazolam 0.05 mg/kg i.m. and ranitidine 2 mg/kg p.o. Anesthesia was induced with fentanyl 50 micrograms/kg administered over 10 min and maintained by a fentanyl infusion 0.2 micrograms.kg-1.min-1. Following endotracheal intubation, a disposable esophageal monitoring probe, equipped with provoking and measuring balloons, was inserted and both the amplitude of provoked (PLEC) and the rate of spontaneous lower esophageal contractions (SLEC) were displayed and recorded. Precisely defined clinical signs of inadequate anesthesia included both somatic and hemodynamic responses to noxious stimulations. The presence of these responses was correlated with PLEC and SLEC and with fentanyl concentrations in plasma at specific times of noxious stimulation during the period preceding initiation of cardiopulmonary bypass. A total of 208 episodes of noxious stimulation were recorded at insertion of the nasal temperature probe (n = 8), at penetration of the skin by towel clips (n = 25), at skin incision (n = 20), at sternotomy (n = 20) and during multiple episodes of electrocauterization (n = 135). These provoked 52 clinical responses.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia, General↗
PubMed1990

Sufentanil and succinylcholine for rapid-sequence anesthetic induction and tracheal intubation: hemodynamic and hormonal responses.

Rapid-sequence induction and tracheal intubation are used in the management of patients at risk of aspiration. Patients with coronary artery disease (CAD) are at additional risk of adverse hemodynamic responses to intubation. The hemodynamic and hormonal responses to intubation with sufentanil, 7 micrograms/kg, and succinylcholine, 1.5 mg/kg, were studied in patients with CAD and good left ventricular function (ejection fraction greater than or equal to 0.4) who were undergoing elective coronary artery bypass grafting. Tracheal intubation occurred 60 seconds after administration of sufentanil and succinylcholine. Heart rate, systemic and pulmonary arterial pressures, pulmonary artery occlusion and central venous pressures, and cardiac outputs were measured at various time intervals before and after induction of anesthesia. Systemic vascular resistance and cardiac index were calculated. Arterial blood samples were drawn before and after anesthetic induction for the determination of catecholamine concentrations in serum. Rapid-sequence administration of sufentanil and succinylcholine resulted in a moderate decrease (24%) in mean arterial pressure from 95 to 72 mm Hg, and the mean arterial pressure remained less than the control value at 1, 3, and 5 minutes after intubation. Systemic vascular resistance also decreased (23%) after administration of sufentanil and returned to control values 5 minutes after intubation. There were no changes in cardiac index until 5 minutes after intubation, at which time it decreased (18%) from 2.8 to 2.3 L/min/m2.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

The anesthesiologist's response to a low-output state after cardiopulmonary bypass: etiologies and remedies.

Artifacts or mechanical problems may cause data which suggest poor myocardial performance during emergence from cardiopulmonary bypass (CPB). Transducer and monitoring equipment malfunctions, damping of the arterial blood pressure tracing, effects of drugs, hypercarbia, inordinately high intrathoracic pressure, cardiac tamponade, and others are all possible culprits. It is important to have a systematic plan for evaluating and interpreting the signs and data that are evident. Causes of hypotension after CPB include low hematocrit, hypercarbia, sympathetic inhibition, vasodilator action, anaphylaxis or anaphylactoid reactions, protamine reactions, and impaired myocardial performance. Impaired myocardial performance can be attributable to rate and rhythm disturbances, inadequate ventricular preload, inappropriately elevated right and left ventricular afterload, and decreased myocardial contractility. Common causes of hypoxemia include a malfunctioning ventilator system, pulmonary problems such as atelectasis and shunt, anemia, and inordinately high utilization of oxygen.

Anesthesia↗
PubMed1990

Making a choice of inotropes and vasodilators in clinical situations.

There are five variables affecting cardiac output: heart rate and rhythm; contractility; ventricular preload; and ventricular afterload. The choice of specific drugs to augment myocardial performance is based on the spectra of their effects on these variables. In order to use inotropes and vasodilators efficiently in clinical situations, it is important to recognize the dose-response relationship, to consider route and rate of administration, and to take into account the presence of other drugs as well as the abnormal pathophysiology of the patient. The safe and effective use of inotropes and vasodilators in critically ill patients is most readily achieved when there is a systematic plan for introducing the drug, evaluating its effects, and adjusting those hemodynamic variables that can be controlled.

Cardiac Output↗
PubMed1989

Is lower esophageal contractility a reliable indicator of the adequacy of opioid anesthesia?

Assessing the adequacy of anesthesia in the patient who is without neuromuscular blockade is usually based on somatic as well as sympathetic and hemodynamic responses to stimulation. Because somatic responses are lost in the patient with neuromuscular blockade, a method is needed to replace these signs as an indicator of inadequate anesthesia. This study attempted to determine the relationship between lower esophageal contractility and somatic signs in detecting inadequate fentanyl anesthesia in 20 patients who were undergoing coronary artery surgery and who were hemodynamically stable in the preoperative period. Premedication included midazolam, 0.05 mg/kg intramuscularly, and ranitidine, 2 mg/kg orally. Anesthesia was induced with fentanyl, 50 micrograms/kg, and maintained by an infusion of fentanyl, 0.2 microgram.kg-1.min-1. After endotracheal intubation, a disposable 24-F esophageal monitoring probe equipped with provoking and measuring balloons was inserted, and both the amplitude of provoked and the rate of spontaneous lower esophageal contractions were displayed and recorded. Inadequate anesthesia was indicated by defined somatic signs in response to noxious stimulation. The presence of these responses was correlated with the amplitude of the provoked and the rate of the spontaneous contractions at five specific times during the period preceding initiation of cardiopulmonary bypass. A total of 208 episodes of stimulation were recorded: at insertion of the nasal temperature probe (n = 8), at skin penetration by towel clips (n = 25), at skin incision (n = 20), at sternotomy (n = 20), and during multiple episodes of electrocauterization (n = 135). These provoked 23 somatic responses. The fentanyl concentration in plasma of the 20 patients during the study period was 30 +/- 10 ng/ml (mean +/- SD).(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia, General↗
PubMed1989

Absence of agonistic or antagonistic effect of flumazenil (Ro 15-1788) in dogs anesthetized with enflurane, isoflurane, or fentanyl-enflurane.

This study determined the effects of flumazenil on the anesthetic requirements (MAC) of the dog for isoflurane (group 1; n = 6), enflurane (group 2; n = 7), and a combination of fentanyl-enflurane (group 3; n = 6). Control MAC in each group was determined by the tail-clamp method. Each animal in groups 1 and 2 received four iv incremental doses of flumazenil: 0.5, 1.0, 1.5, and 4.5 mg/kg, and isoflurane MAC or enflurane MAC was determined after each dose. The animals in group 3 received a loading dose and a continuous infusion of fentanyl 0.8 micrograms.kg-1.min-1 over 8 h, and enflurane MAC was determined four times during this experimental period. After the fourth enflurane MAC determination in each animal of group 3, a single iv dose of flumazenil 1.5 mg/kg was injected and enflurane MAC was then determined for the last time. In the incremental doses administered, flumazenil did not demonstrate any agonistic or antagonistic interaction with isoflurane, enflurane, or the fentanyl-enflurane combination. In group 3, plasma fentanyl concentrations remained stable at 12.5 +/- 3.0 ng/ml (mean +/- SD) throughout the experiment and reduced enflurane MAC by 60 +/- 8%. The addition of flumazenil changed neither the fentanyl concentration in plasma (12.2 +/- 3.8 ng/ml) nor its reduction of enflurane MAC (61 +/- 7%). In conclusion, the absence of effect of flumazenil on the MAC of enflurane, isoflurane, or a fentanyl-enflurane combination suggests that they do not interact with the benzodiazepine receptor.

Anesthesia, Intravenous↗
PubMed1989

Anesthetic interactions of midazolam and fentanyl: is there acute tolerance to the opioid?

The anesthetic effects and interactions of midazolam and fentanyl were determined in terms of their reduction of enflurane MAC in dogs, and the effects of their specific antagonists were also investigated. Control enflurane MAC was determined by the tail clamp method in 18 mongrel dogs. Each animal then received an iv loading dose of midazolam followed by a constant infusion at 9.6 micrograms.kg-1.min-1 designed to produce a stable enflurane MAC reduction of approximately 40%, and enflurane MAC was determined following a 60-min observation period during which time the midazolam concentration in plasma stabilized. Fentanyl was then administered in a series of three incremental loading doses (15, 30, and 225 micrograms/kg) and infusions (0.05, 0.2, and 3.2 micrograms.kg-1.min-1) designed to produce enflurane MAC reductions of 30%, 50%, and 65%, respectively. Enflurane MAC was again determined following a 60-min observation period for each new infusion. In nine dogs after the fourth determination of enflurane MAC, fentanyl was discontinued and 1 mg/kg naloxone was administered iv every 10 min until enflurane MAC was determined for the last time. In the other nine dogs, midazolam was discontinued and 1.5 mg/kg flumazenil (RO 15-1788) was administered and enflurane MAC determined for the last time. The midazolam concentration in plasma remained stable at 414 +/- 134 ng/ml throughout the study, and in the absence of fentanyl reduced enflurane MAC by 40 +/- 10% (mean +/- SD). The addition of fentanyl produced significant further reductions in enflurane MAC.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia, Inhalation↗
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↗