Effects of supplemental dietary tannins on the performance of white-tailed deer (Odocoileus virginianus).

Tannins are natural and nutritionally significant components of the diets of browsing ungulates. In trials on supplemented pastures and in drylots, we estimated dry matter intake (DMI), weight gain, and urea N, potassium, cortisol and creatinine in urine of captive white-tailed deer fed pelleted diets that differed only in the respective quebracho tannin (QT) content. The low control, medium and high QT rations were 3.6, 63 and 152 g/kg DM respectively. There was no tannin-free pellet option. Trials were divided into winter pasture, restricted choice and spring growth. In winter pasture trial on pasture using QT, deer reduced QT intake relative to that expected under random foraging. This aversion was also apparent during the spring growth trial. While DMI in the winter pasture trial remained similar among treatments (p > 0.05), averaging 130 g/kg(0.75)/day, deer gained more weight (p < 0.05) when given a choice that included the high QT ration. During subsequent spring growth, DMI and weight gains generally exceeded those of the winter period. Unlike the winter pasture trial, weight gains in spring growth trial were higher (p < 0.05) in the low-control QT treatment. In the restricted choice trial, weight gain was again higher (p < 0.05) for deer fed a low-control QT diet. The urea N/creatinine ratio of deer fed the low-control QT diet (0.0357) was over three times that of deer fed the high QT diet (0.0107). Neither potassium/creatinine nor cortisol/creatinine ratios were affected by diet (p > 0.05). Collectively, these results suggest that although deer do not avoid tannins, and even ingested up to 5% under the choice options in these trials, the effect of tannins on deer performance may vary by season as well as by foraging opportunities.

Performance and dietary preferences of white-tailed deer grazing chicory, birdsfoot trefoil or alfalfa in north central Alberta.

Little information exists on the performance of deer on alternative forage species in northern temperate environments during summer and fall, the period of inherent maximum growth in deer. In performance and choice experiments, we compared live weight gain (g/kg(0.75)/day), absolute [kg/ha dry matter (DM)] and relative (% DM) herbage utilization, relative preference index (RPI) as well as plant community visitation of white-tailed deer grazing alfalfa (Medicago sativa), birdsfoot trefoil (Lotus corniculatus) or chicory (Cichorium intybus) in north central Alberta, Canada. Herbage phytomass and quality was also measured on the grazed pastures. Alfalfa had higher dry matter yields and crude protein concentrations than chicory and trefoil. Chicory had lower neutral detergent fiber concentrations than the other forages. Tannin concentrations were greatest in birds foot trefoil (nearly 55 g/kg DM), well above those in the other forages (<5 g/kg DM). Live weight gain was similar among deer feeding within the paddocks seeded to birds foot trefoil and chicory, and more than two times higher (p < 0.05) than deer feeding in paddocks seeded to alfalfa. Deer spent more grazing time (about 40%) on chicory pastures than on alfalfa and birds foot trefoil pastures. RPI values were greatest for birds foot trefoil at 2.11, intermediate for chicory at 1.40, and lowest for alfalfa at <0.60. Absolute herbage utilization remained similar (p > 0.05) among the three forage species. In contrast, relative herbage utilization was greater from birds foot trefoil (52% DM) than chicory (40% DM) or alfalfa (25% DM). These results suggest that the use of alfalfa with other alternative forages may prove beneficial to deer production, rather than using alfalfa pasture alone.

Extraction of condensed tannins from cervid feed and feces and quantification using a radial diffusion assay.

A radial diffusion assay was employed to quantify condensed tannins (CT) in feed and feces of mule deer (Odocoileus hemionus) and white-tailed deer (O. virginianus). This biological assay measures the precipitation of bovine serum albumin (BSA), with the area of the precipitation ring being proportional to the amount of extracted CT applied to the well. CT extracted from the bark of white spruce (Picea glauca) was used as the standard. CT were extracted with 70% (v/v) aqueous acetone and precipitated with 50% (v/v) aqueous methanol or 70% (v/v) aqueous acetone. Functional range of CT weights for suitable ring measurement was 0.5-4.0 mg, and equilibrium was achieved within an incubation period of 24 hr. Methanol (50%) was a more effective precipitation solvent than acetone (70%) having 13 +/- 4% greater specific activity (P < 0.05) and superior capabilities for predicting CT content. Precipitation rings were evaluated on images magnified on a photocopier. Ring diameters measured on a 200% enlarged photocopy provided the most precise estimate of ring area (R2 = 0.98). This convenient method reduced analysis times and enhanced accuracy and precision of tannin quantification. Analytical consequences and future research requirements are considered.

Pharmacokinetics of sufentanil in patients undergoing coronary artery bypass graft surgery.

OBJECTIVE: To determine the pharmacokinetics of sufentanil in patients undergoing coronary artery bypass graft surgery. DESIGN: Prospective, multigroup study. SETTING: University-affiliated hospital. PARTICIPANTS: Patients with good left ventricular function undergoing elective surgery (n = 103). INTERVENTIONS: Sufentanil was administered by target-controlled infusion, with target effect-site concentrations ranging from 0.4 to 4.5 ng/mL. Isoflurane was administered as required to maintain stable hemodynamics. Sufentanil pharmacokinetics were determined by population modeling. The potential effects of gender, weight, different premedications (lorazepam, morphine-scopolamine, or clonidine), and coinduction with propofol on sufentanil pharmacokinetics were explored. MEASUREMENTS AND MAIN RESULTS: The first model determined was a simple 3-compartment model, without any covariates, which had these parameters: V(1) = 5.7 L, V(2) = 18.1 L, V(3) = 225 L, Cl(1) = 0.69 L/min, Cl(2) = 3.1 L/min, and Cl(3) = 1.4 L/min. The overall predictive ability during the entire pre-cardiopulmonary bypass period of this model was excellent, with virtually no bias (median prediction error, -0.4%) and good precision (median absolute prediction error, 18.4%). More complex models with the various premedications used or coinduction with propofol as covariates did not improve the predictive accuracy or precision compared with the simple 3-compartment model. Similarly, including either gender or weight as a covariate did not improve predictive ability. CONCLUSION: The authors have determined a pharmacokinetic model for sufentanil that can be used to maintain desired target concentrations of sufentanil before cardiopulmonary bypass, with a high degree of accuracy and acceptable variability. Concomitantly administered medications (lorazepam, morphine-scopolamine, clonidine, or propofol) do not appear to have any clinically important effects on distribution-phase sufentanil pharmacokinetics.

Hired, fired, and not retired: an interview with a physician executive who has run the career gauntlet. Interview by Richard L. Reece.

Richard L. Reece, MD, interviewed Robert J. Hudson, MD, on April 24, 2000 to discuss his experiences as a physician executive who has made the career transition from practicing physician to managed care executive to biotech entrepreneur. Along the way, he's hired and fired others, and been fired himself. Painful as it is, many physician executives' career realities include being fired. Organizations, after all, are living organizations--they grow, wither, and molt. And as they molt, organizations shed and regrow new skin. What do physician executives do when they've been fired? They go through their own cycle and retreat, reflect, and re-emerge, often reinventing themselves as they go. An essential part of this process is looking within to plumb likes and dislikes, strengths and weaknesses, nightmares and dreams, and positive and negative experiences. For most executives, out of these experiences has come a circle of friends and a Rolodex. Start by reaching out to the circle, by going through your Rolodex, and you can broadcast the news of your rebirth.

A comparison of fentanyl and sufentanil in patients undergoing coronary artery bypass graft surgery.

OBJECTIVE: To compare fentanyl and sufentanil, administered in equipotent concentrations by target-controlled infusion, as components of a balanced anesthetic in patients undergoing coronary artery bypass graft (CABG) surgery. DESIGN: A prospective, randomized, double-blind trial. SETTING: A university hospital. PARTICIPANTS: Twenty-one patients undergoing nonemergent, primary CABG surgery. INTERVENTIONS: Patients received fentanyl (group F, n = 10) or sufentanil (group S, n = 11) by target-controlled infusion throughout the pre-cardiopulmonary bypass (CPB) period. To ensure equipotency, the target effect-site concentrations employed (fentanyl, 8.1 ng/mL, and sufentanil, 0.68 ng/mL) were equal to the IC50 for electroencephalographic effect. Isoflurane was administered as needed to maintain pre-CPB hemodynamics near preoperative baseline values. MEASUREMENTS AND MAIN RESULTS: Hemodynamics and end-tidal isoflurane concentration were measured every 15 to 30 seconds. Serum opioid concentrations were measured 5 times between induction and CPB. Opioid cost was based on the number of ampules opened to provide the administered dose. The 2 groups were similar demographically. The pre-CPB serum opioid concentrations were constant and averaged fentanyl, 5.8 +/- 1.9 ng/mL, and sufentanil, 0.59 +/- 0.13 ng/mL. Pre-CPB hemodynamics were stable and similar in both groups. Pre-CPB end-tidal isoflurane requirements did not differ between groups and averaged 0.46 +/- 0.21% in group F and 0.56 +/- 0.24% in group S. The duration of post-operative endotracheal intubation was 9.1 +/- 5.0 hours in group F and 8.0 +/- 3.2 hours in group S (p = NS). The cost per patient of fentanyl (Canadian $6.12 +/- 1.04) was less than that of sufentanil (Canadian $17.47 +/- 4.65). CONCLUSIONS: When administered in a constant 10:1 concentration ratio, fentanyl and sufentanil do not differ in their ability to facilitate pre-CPB hemodynamic control. Although both opioids were relatively inexpensive, the acquisition cost of fentanyl was less than sufentanil. A recommendation regarding the opioid of choice for routine use in patients undergoing CABG surgery awaits more rigorous studies of recovery and cost after equipotent doses of fentanyl and sufentanil. When combined with isoflurane, effect-site opioid concentrations near the IC50 for electroencephalographic effect provide excellent pre-CPB hemodynamic control in patients undergoing CABG surgery.

Does sufentanil concentration influence isoflurane requirements during coronary artery bypass grafting?

OBJECTIVE: To search for concentration-related suppression of hemodynamic responsiveness by sufentanil. DESIGN: Prospective, randomized, double-blind study. SETTING: University hospital. PARTICIPANTS: Patients undergoing elective coronary artery bypass grafting (CABG). INTERVENTION: Patients were assigned to target effect-site sufentanil concentrations of 1.5 ng/mL (group L; n = 14), 3.0 ng/mL (group M; n = 13), or 4.5 ng/mL (group H; n = 12). Sufentanil was administered by computer-assisted continuous infusion. Isoflurane was used to maintain intraoperative hemodynamics near preoperative values. MEASUREMENTS AND MAIN RESULTS: Hemodynamics, the electroencephalographic spectral edge (SE95), and end-tidal isoflurane concentration (ET-ISO) were measured every 10 to 30 seconds during the prebypass period. Serum sufentanil concentration was measured at intervals. Prebypass serum sufentanil concentrations were stable, averaging 3.0 +/- 0.7, 5.1 +/- 1.1, and 7.1 +/- 1.3 ng/mL in groups L, M, and H, respectively. The groups did not differ with respect to the speed of induction, intraoperative hemodynamics, incidence of isoflurane use, or isoflurane concentrations required. ET-ISO and serum sufentanil levels were not correlated. Among seven group L patients who did not require isoflurane, the average prebypass serum sufentanil concentration ranged from 1.7 to 3.3 ng/mL. CONCLUSION: Sufentanil does not induce concentration-related suppression of hemodynamic responsiveness over the range studied. A stable serum sufentanil concentration of 3.0 +/- 0.7 ng/mL induces the maximal opioid effect and need not be exceeded in patients undergoing CABG. A sufentanil concentration of 1.7 ng/mL provides clinically adequate anesthesia without supplementation in some premedicated patients undergoing CABG.

Evaluation of life-cycle herd efficiency in cow-calf systems of beef production.

A deterministic beef efficiency model (BEM) was used to evaluate life-cycle herd efficiency (LCHE) in cow-calf beef production systems using four breed groups of beef cattle. The breed groups were Beef Synthetic #1 (SY1), Beef Synthetic #2 (SY2), Dairy Synthetic (DS), and purebred Hereford (HE). The LCHE was defined over the lifetime of the herd as the ratio of total output (lean meat equivalent) to total input (feed equivalent). Breed differences in LCHE were predicted with the larger/slower maturing DS being most efficient at each age of herd disposal and reproductive rate. This was mainly because, at any average age at culling, the dams of DS breed group were less mature and so had been carrying relatively lower maintenance loads for shorter periods and positively influencing LCHE. Higher LCHE was predicted with improvement in reproductive performance if there were no associated extra costs. However, this declined markedly if there was a delay in marketing of offspring. As average age at culling increased from 4 to 6 yr, efficiency declined sharply, but it began to recover beyond this age in most breed groups. We concluded that the slower maturing DS breed group may be more efficient on a herd basis in cow-calf systems and that improvements in reproductive rate not associated with extra costs improve life-cycle efficiency. Culling cows soon after their replacements are produced seems efficient.

Bioaccumulation of mercury in pelagic freshwater food webs.

Current paradigms regarding the bioaccumulation of mercury are rooted in observations that monomethyl mercury (meHg) biomagnifies along pelagic food chains. However, mechanisms regulating the formation of meHg, its initial incorporation at the base of pelagic food chains, and its subsequent trophic transfer remain controversial. Here we use field data from 15 northern Wisconsin lakes, equilibrium aqueous speciation modeling, and statistical modeling to revisit several hypotheses about the uptake, distribution, and fate of inorganic Hg (HgII) and meHg in aquatic biota. Our field data comprise determinations of total Hg (HgT) and meHg in surface waters, sediments, microseston, zooplankton, and small fish in each of the study lakes. For these lake waters, strong positive correlations between DOC and aqueous concentrations of mercury along with negative correlations between DOC and the seston-water partitioning of mercury indicate that organic ligands bind HgII and meHg strongly enough to dominate their apparent aqueous speciation. In the microseston, zooplankton and fish, meHg concentrations and bioaccumulation factors (BAFs) increased with increasing trophic level while biotic concentrations of HgII decreased--indicating that meHg was indeed the biomagnified species of mercury. For all trophic levels, meHg concentrations varied positively with the calculated aqueous concentration of meHg+ (free ion), especially when coupled with pH, or meHgOH (hydroxide) species but not with meHgCl0, the neutral chloride complex. These findings suggest that: (1) the passive uptake of meHg does not control bioaccumulation at the base of aquatic food webs in nature (i.e. phyto- and bacterioplankton); (2) correlation with pH and DOC largely reflect the supply and bioavailability of meHg to lower trophic levels; and (3) meHg concentrations at higher trophic levels reflect uptake at low trophic levels and other factors, such as diet and growth. Low concentrations of meHg in surficial sediments indicate that the fates of biotic HgII and meHg are different. Most biotic meHg is demethylated rather than buried in lake sediments.

Isolation, characterization and localization of glycosaminoglycans in growing antlers of wapiti (Cervus elaphus).

Glycosaminoglycans were isolated from the four sections (tip, upper, middle and base) of the main beam of growing antlers of wapiti (Cervus elaphus) by papain digestion and DEAE-Sephacel chromatography. Chondroitin sulfate was the major glycosaminoglycan in each section of antler accounting for, on average, 88% of the total uronic acid. The yield of chondroitin sulfate liberated from the tissue was approximately 6-fold greater in the cartilaginous (tip and upper) sections than in the bony (middle and base) sections. This was consistent with the higher intensity of glycosaminoglycan staining with either Alcian Blue or Safranin-O. The majority (average 88%) of chondroitin sulfate was precipitated with 40 and 50% ethanol. The average molecular size of chondroitin sulfate determined by gel chromatography on Sephacryl S-300 tended to be greater in the 40% ethanol than in the 50% ethanol fraction. In either fraction, the molecular size of chondroitin sulfate was smaller in cartilaginous tissues than in osseous tissues of growing antler. In addition to chondroitin sulfate, the antler contained small amounts of hyaluronic acid, dermatan sulfate and keratan sulfate. The immunohistochemical study showed wide distribution of chondroitin sulfate, decorin, and keratan sulfate throughout the antler. On the other hand, keratan sulfate was more prominent in the cartilaginous sections than in the bony sections where the anti-keratan sulfate monoclonal antibody staining was seen in the osteoid tissue only.

Concentration-response relationships for fentanyl and sufentanil in patients undergoing coronary artery bypass grafting.

BACKGROUND: Concentration-response relationships for sufentanil and fentanyl are undefined in patients undergoing coronary artery bypass grafting. METHODS: Separate studies of sufentanil and fentanyl were performed in lorazepam-premedicated patients undergoing coronary artery bypass grafting. Patients were assigned randomly to groups with different prebypass effect-site opioid concentrations targeted by computer-assisted infusion. The target sufentanil concentrations were 0.4 ng/ml (group LS, n = 11), 0.8 ng/ml (group MS, n = 10), and 1.2 ng/ml (group HS, n = 11); the target fentanyl concentrations were 5 ng/ml (group LF, n = 7), 10 ng/ml (group MF, n = 7), and 15 ng/ml (group HF, n = 6). Propofol at a dose of 1 mg/kg was administered at induction of anesthesia and isoflurane was used for hemodynamic control Hemodynamics, end-tidal isoflurane concentration, and opioid concentration in arterial blood were measured at specific intervals. RESULTS: Intraoperative opioid concentrations were constant, averaging 0.71 +/- 0.13, 1.25 +/- 0.21, and 2.03 +/- 0.46 ng/ml for groups LS, MS, and HS, respectively, and 7.3 +/- 1.1, 13.2 +/- 2.2, and 24.4 +/- 5.8 ng/ml for groups LF, MF, and HF, respectively (all mean +/- SD). Isoflurane requirements were significantly greater in group LS than in groups MS and HS and greater in group LF than in groups MF and HF. The serum opioid and end-tidal isoflurane concentrations were correlated significantly. There were no intergroup differences in hemodynamics. CONCLUSIONS: Serum sufentanil and fentanyl concentrations of 0.71 +/- 0.13 ng/ml and 7.3 +/- 1.3 ng/ml, respectively, are on the steep parts of the concentration-response relationships and facilitate prebypass hemodynamic control in patients undergoing coronary artery bypass grafting with opioid-isoflurane anesthesia. Concentrations of sufentanil > or = 1.25 +/- 0.21 ng/ml and of fentanyl > or = 13.3 +/- 2.2 ng/ml minimize isoflurane requirements but do not improve hemodynamic control.

A comparison of clonidine with conventional preanesthetic medication in patients undergoing coronary artery bypass grafting.

UNLABELLED: In this controlled study, we compared clonidine with conventional premedication in 35 patients undergoing coronary artery bypass grafting (CABG). After premedication with clonidine 5 microg/kg p.o. (Group C, n = 11), lorazepam 60 microg/kg p.o. (Group L, n = 13), or morphine 0.1 mg/kg plus scopolamine 6 microg/kg i.m. (Group M, n = 11), sedation, anxiety, and quality of premedication were graded. After the administration of sufentanil 2.0 microg/kg over 12.5 min, a computer-assisted infusion device targeted a sufentanil effect-site concentration of 0.75 ng/mL. Hemodynamic variables, end-tidal isoflurane concentration (ET-ISO), the electroencephalographic spectral edge, and the serum sufentanil concentration (SUF) were measured. There were no intergroup differences in anxiety, sedation, quality of premedication, the dose of sufentanil causing unconsciousness, or the electroencephalographic (EEG) response to induction. Intraoperative SUF was stable, with no intergroup difference. The average prebypass ET-ISO was lower in Group C than in Group M. The ET-ISO and peak ET-ISO after intense surgical stimulation were lower in Group C versus Groups L and M. Mean arterial blood pressure was lower in Group C versus Groups L and M. There were no intergroup differences in pharmacologic intervention, time to extubation, or intensive care unit stay. Clonidine produces sedation, anxiolysis, and quality of premedication comparable to conventional premedication. Compared with other drugs, clonidine does not alter the dose of sufentanil inducing unconsciousness or EEG slowing, but it uniquely reduces isoflurane requirements. IMPLICATIONS: In patients undergoing coronary artery bypass grafting, clonidine produces sedation and relieves anxiety as effectively as conventional premedication. Clonidine does not uniquely alter the dose of sufentanil inducing unconsciousness or electroencephalographic slowing, but it significantly reduces isoflurane requirements.

Dose-response to anaesthetic induction with sufentanil: haemodynamic and electroencephalographic effects.

PURPOSE: To determine the effect of a five-fold variation in sufentanil dose on the haemodynamic and electroencephalo graphic (EEG) response to anaesthetic induction and tracheal intubation. METHODS: Thirty-four patients undergoing elective coronary artery bypass grafting (CABG) participated in this randomized double-blind study. Patients in Group L (n = 17) received 3 micrograms.kg-1 sufentanil and those in Group H (n = 17) 15 micrograms.kg-1. Premedication was 60 micrograms.kg-1 lorazepam po. Anaesthesia and neuromuscular blockade were induced by infusing sufentanil and 0.15 mg.kg-1 vecuronium i.v. over five minutes. Haemodynamic data and the electroencephalographic (EEG) spectral edge were acquired by computer and compared at Control, Induction and Intubation. RESULTS: Sufentanil dose did not affect the haemodynamic or EEG response at end-induction. No bradyarrhythmias occurred, and the incidence of hypotension was 12% in both groups. However, during induction apparent electromyographic artifacts and a transiently greater increase in heart rate were observed in Group H. The serum sufentanil concentration at Induction was 6.1 +/- 1.8 ng.ml-1 in Group L and 25.4 +/- 8.8 ng.ml-1 in Group H, and did not correlate with haemodynamic changes. No patient recalled any intraoperative event. CONCLUSION: Increasing sufentanil dose from 3 to 15 micrograms-1 does not influence the ultimate haemodynamic response to induction. Combined with lorazepam premedication, 3 micrograms-1 sufentanil produces near-maximal haemodynamic and EEG effects and is adequate for induction and tracheal intubation of patients undergoing CABG. Sufentanil 15 micrograms.kg-1 is no more efficacious, and causes transient cardiovascular stimulation.

High-dose thiopentone for open-chamber cardiac surgery: a retrospective review.

PURPOSE: High-dose thiopentone has been reported to reduce the incidence of neurological dysfunction after open-chamber cardiac surgery. However, this technique delays tracheal extubation and increases requirements for inotropic support after cardiopulmonary bypass. As a quality assurance measure to determine the safety of high-dose thiopentone, we reviewed the records of all patients undergoing elective, open-chamber surgery at our institution between 1st March, 1987 and 31st Dec, 1989. METHODS: The charts of 236 patients were reviewed retrospectively, and 227 met our inclusion criteria. The perioperative characteristics of patients anaesthetized with thiopentone (Group T, n = 80) were compared with those of patients anaesthetized with opioids (Group O, n = 147). RESULTS: Anaesthetic technique was chosen by the attending anaesthetist. in Group T (n = 80) thiopentone 38.1 +/- 11.8 mg.kg-1 was infused to produce electroencephalographic burst-suppression during bypass. Moderate hypothermia and arterial line filtration were used during bypass. The groups did not differ with respect to demographics, type of surgery, or conduct of bypass. There were no strokes in Group T and 4 in Group O (P = NS). The time to extubation was prolonged in Group T compared with Group O (39 +/- 51 vs 27 +/- 24 h, P = 0.014), as was the duration of stay in intensive care (66 +/- 56 vs 51 +/- 29 h, P = 0.010). Thiopentone did not increase the need for inotropic or mechanical support after bypass. In-hospital mortality was lower in Group T than in Group O (1.2% vs 9.5%, P = 0.034). CONCLUSION: High-dose thiopentone delays extubation after open-chamber procedures. However, the technique appears safe, and further prospective investigation is justifiable.

Midazolam pharmacokinetics in patients undergoing abdominal aortic surgery.

Fentanyl and its analogs are eliminated slowly by patients having abdominal aortic surgery. This is principally due to larger volumes of distribution, compared to the pharmacokinetics determined in other surgical patients. Midazolam, like these opioids, is a lipophilic organic base, suggesting that it may also have a larger volume of distribution in patients undergoing abdominal aortic reconstruction. The pharmacokinetics of intravenous midazolam, 0.25 mg/kg, were determined in patients undergoing elective infrarenal abdominal aortic surgery. The mean (+/- SD) age of the patients was 66.7 +/- 9.2 yr, and their mean weight was 74.3 +/- 12.7 kg. Blood samples were drawn at increasing intervals for 24 h after administration of midazolam, and serum midazolam concentrations were measured by gas-liquid chromatography. A 3 compartment model best described the concentration versus time data. Simulations of the times required for 20%, 50%, and 80% decreases in midazolam concentrations after stopping an infusion that maintains a constant plasma midazolam concentration were performed, comparing pharmacokinetic variables from this study with previously published values. Metabolic clearance was 361 +/- 97 mL/min. Rapid intercompartmental clearance was 2197 +/- 997 mL/min and slow intercompartmental clearance, 481 +/- 225 mL/min. The volume of the central compartment (Vc) and the volume of distribution at steady state (Vdss) were 5.8 +/- 5.3 L and 118.2 +/- 70.4 L, respectively. The elimination half-life was 6.3 +/- 3.6 h, 1.5- to 3-fold longer than has been previously reported in patients undergoing surgery. Compared to previously published studies of other groups of patients, metabolic clearance of midazolam was slower in patients undergoing abdominal aortic surgery.(ABSTRACT TRUNCATED AT 250 WORDS)

Drug interactions with sufentanil. Hemodynamic effects of premedication and muscle relaxants.

Induction of anesthesia with synthetic opioids is occasionally accompanied by undesirable hemodynamic changes such as tachycardia and hypertension, or bradycardia and hypotension. We hypothesized that drug interactions cause many of these adverse responses. Therefore, we conducted a randomized double-blind study to investigate the interactive effect of premedication and muscle relaxants on the hemodynamic response to induction with intravenous (iv) sufentanil 10 micrograms.kg-1. Eighty patients with left ventricular ejection fraction greater than or equal to 0.40, undergoing elective coronary artery surgery, were premedicated with either morphine 0.1 mg.kg-1 and scopolamine 6 micrograms.kg-1 intramuscularly, or lorazepam 60 micrograms.kg-1 orally, and paralyzed with either pancuronium 0.1 mg.kg-1 or vecuronium 0.1 mg.kg-1 iv. The four treatment groups were SP (morphine-scopolamine + pancuronium), LP (lorazepam + pancuronium), SV (morphine-scopolamine + vecuronium), and LV (lorazepam + vecuronium). Hemodynamics were recorded at three time periods: 1) control, 2) induction, and 3) intubation. Premedication-relaxant interactions significantly affected hemodynamics. In group SP, mean heart rate (HR) increased significantly on induction (56 +/- 11 to 69 +/- 13 beats.min-1), while mean arterial pressure (MAP) and cardiac index (CI) were unchanged. HR, MAP, and CI were significantly higher after induction in group SP compared to the other three groups. In group LP, mean HR increased less than in group SP (56 +/- 8 to 62 +/- 14 beats.min-1), whereas MAP and CI declined significantly. In group SV, HR and CI were unchanged, but MAP declined significantly. In group LV, HR was stable, whereas both MAP and CI declined significantly. The incidence of pharmacologic interventions during the study period also differed significantly among groups.(ABSTRACT TRUNCATED AT 250 WORDS)