Microg Kg-1 Research Articles

Plasma and Tissue Depletion of Florfenicol and Florfenicol-amine in Chickens

Chickens were used to investigate plasma disposition of florfenicol after single intravenous (i.v.) and oral dose (20 mg kg-1 body weight) and to study residue depletion of florfenicol and its major metabolite florfenicol-amine after multiple oral doses (40 mg kg-1 body weight, daily for 3 days). Plasma and tissue samples were analyzed using a high-performance liquid chromatography (HPLC) method. After i.v. and oral administration, plasma concentration-time curves were best described by a two-compartment open model. The mean [ +/- standard deviation (SD)] elimination half-life (t1/2beta) of florfenicol in plasma was 7.90 +/- 0.48 and 8.34 +/- 0.64 h after i.v. and oral administration, respectively. The maximum plasma concentration was 10.23 +/- 1.67 microg mL-1, and the interval from oral administration until maximal concentration was 0.63 +/- 0.07 h. Oral bioavailability was found to be 87 +/- 16%. Florfenicol was converted to florfenicol-amine. After multiple oral dose (40 mg kg-1 body weight, daily for 3 days), in kidney and liver, concentrations of florfenicol (119.34 +/- 31.81 and 817.34 +/- 91.65 microg kg-1, respectively) and florfenicol-amine (60.67 +/- 13.05 and 48.50 +/- 13.07 microg kg-1, respectively) persisted for 7 days. The prolonged presence of residues of florfenicol and florfenicol-amine in edible tissues can play an important role in human food safety, because the compounds could give rise to a possible health risk. A withdrawal time of 6 days was necessary to ensure that the residues of florfenicol were less than the maximal residue limits or tolerance established by the European Union.

Granisetron/dexamethasone combination for the prevention of postoperative nausea and vomiting after laparoscopic cholecystectomy

Abstract Dexamethasone decreases chemotherapy-induced emesis when added to an antiemetic regimen. This study was undertaken to evaluate the efficacy of granisetron/dexamethasone combination for preventing postoperative nausea and vomiting (PONV) after lapIaroscopic cholecystectomy (LC). In a prospective, randomized, double-blind manner, 120 patients (83 females), aged 25-65 years, were assigned to receive granisetron 40 microg kg-1 alone or granisetron 40 microg kg-1 plus dexamethasone 8 mg (n=60 of each) intravenously immediately before the induction of anaesthesia. A standardized general anaesthetic procedure and postoperative analgesia were used. A complete response, defined as no PONV and no need for another rescue antiemetic, during 0-3 h after anaesthesia was 83% with granisetron and 98% with granisetron plus dexamethasone, respectively (P=0.008); the corresponding incidence during 3-24 h after anaesthesia was 83% and 98% (P=0.008). No clinically important adverse events were observed in any of the group. In conclusion, prophylactic therapy with granisetron/dexamethasone combination is more effective than granisetron alone for the prevention of PONV after LC.

Addition of remifentanil to patient-controlled tramadol for postoperative analgesia

We have investigated whether, after major abdominal surgery, the addition of remifentanil to tramadol for intravenous patient-controlled analgesia improved analgesia and lowered pain scores, compared to a patient-controlled analgesia containing only tramadol. Sixty-two patients were allocated randomly to receive an intravenous patient-controlled analgesia with tramadol alone (T), or tramadol plus remifentanil (TR), in a double-blind randomized study. Whenever patients complained of pain, they were allowed to use bolus doses of tramadol (0.2 mg kg-1) or tramadol (0.2 mg kg-1) plus remifentanil (0.2 microg kg-1) mixture every 10 min without a time limit and background infusion. Discomfort, sedation, pain scores, total and bolus patient-controlled analgesia tramadol consumption, and side-effects were recorded for up to 24 h after the start of patient-controlled analgesia. Pain scores at rest were statistically significantly lower in the TR group at 6, 12 and 24 h than in T group (P < 0.05). Pain scores at movement and patient comfort scores were also found to be significantly lower in the TR group at 2, 6, 12 and 24 h than in the T group (P < 0.05). Although the TR group consumed less tramadol, there were no statistically significant differences in the cumulative tramadol consumptions between the groups at any time. However, the number of patients requiring rescue analgesia and average supplementary doses used was significantly higher in the T group than in the TR group (P < 0.05). After major abdominal surgery, adding remifentanil (0.2 microg kg(-1)) to tramadol (0.2 mg kg(-1)), with 10-min lockout times, for patient-controlled analgesia offered better postoperative pain relief and patient comfort, without causing any sedation or respiratory depression.

The effects of isoflurane on adrenomedullin-induced haemodynamic responses in pithed rats

Adrenomedullin is a potent vasodilatory peptide. The mechanisms of adrenomedullin-induced responses are via guanine nucleotide guanosine 5'-triphosphate-binding protein (G-protein)-coupled receptor activation and are similar to those of calcitonin gene-related peptide (CGRP). Previously, we reported that sevoflurane and isoflurane inhibit CGRP-induced haemodynamic responses. The effects of volatile anaesthetics on adrenomedullin-induced haemodynamic responses, however, are unclear. We hypothesized that the volatile anaesthetic isoflurane inhibits adrenomedullin-induced haemodynamic responses. We studied the effects of isoflurane on adrenomedullin-induced haemodynamic responses in pithed rats, which enables us to evaluate the direct cardiovascular effects of drugs without interference from centrally mediated circulatory reflexes. Male Wistar rats were pithed by inserting a stainless-steel rod into the spinal cord. Following median sternotomy, a flow probe was placed around the ascending aorta to measure aortic blood flow. Mean arterial pressure and cardiac output were maintained at approximately 100 mmHg and 50 mL min-1, respectively, with continuous infusion of norepinephrine. After 30 min inhalation of isoflurane (1%, or 2%) in oxygen, or only oxygen, adrenomedullin (1, 3, 10 or 30 microg kg-1) was administered intravenously. Adrenomedullin administration induced a transient increase followed by a persistent decrease in mean arterial pressure and cardiac output. Isoflurane (2%) significantly inhibited the initial increase in mean arterial pressure and the later decrease in mean arterial pressure and systemic vascular resistance. Isoflurane inhibits adrenomedullin-induced vasodilation and positive inotropic effect in pithed rats. Isoflurane might inhibit the adrenomedullin receptor-mediated response, which is a common pathway for both actions.

Effects of dexmedetomidine infusion in patients undergoing functional endoscopic sinus surgery under local anaesthesia

Functional endoscopic sinus surgery can be performed under either local or general anaesthesia. The objective of this study was to investigate the haemodynamic effects of perioperatively administered dexmedetomidine, a new generation alpha-2-agonist, in patients for functional endoscopic sinus surgery. Sixty-two patients who were planned to undergo functional endoscopic sinus surgery under local anaesthesia were included in the study. Following meperidine premedication, both groups were monitored in a standard manner with electrocardiogram, non-invasive blood pressure and percentages of peripheral saturation of oxygen. Saline intravenous infusion was started in the placebo group, and dexmedetomidine bolus intravenous infusion (an initial loading dose of 1 microg kg-1 given for a 10-min period followed by 0.7 microg kg-1 h-1) was administered to the treatment group. Maintenance dose infusion was stopped 15 min before the end of the surgical procedure. Systolic, diastolic and mean arterial pressures, and heart rate markedly decreased in the dexmedetomidine group. However, dexmedetomidine had no effect on serum nitric oxide levels, measured by a nitric oxide/ozone chemiluminescence method. No significant difference was found in oxygen saturation levels of the two groups. Postoperative nausea and vomiting rates were significantly lower in the dexmedetomidine group. No adverse effects were observed with this alpha-2-agonist. Dexmedetomidine provided appropriate levels of sedation. These results suggest that dexmedetomidine provides analgesia, adequate sedation and surgical comfort without adverse effects for patients undergoing functional endoscopic sinus surgery under local anaesthesia.

Scheduled prophylactic ondansetron administration did not improve its antiemetic efficacy after intracranial tumour resection surgery in children

Postoperative nausea and vomiting after craniotomy may increase intracranial pressure and morbidity in children. This prospective, randomized, placebo-controlled and double-blinded study was designed to evaluate the antiemetic efficacy of prophylactic ondansetron after intracranial tumour resections in children.Ninety children were divided into three groups and received saline (Group 1), ondansetron 150 microg kg-1 intravenously at dural closure (Group 2) or two doses of ondansetron 150 microg kg-1 intravenously, the second dose repeated after 6 h (Group 3). Episodes of nausea, emesis and side-effects were noted for 24 h postoperatively.Overall 24 h incidence of postoperative nausea and vomiting was not significantly different among the three groups (9 (37.5%) in Group 1 vs. 7 (27%) in Group 2 and 8 (32%) in Group 3, P = 0.73). No difference in rescue antiemetic treatment or postoperative nausea and vomiting at specific time intervals (0-6 and 6-24 h postoperative period) was seen among the three groups. No significant side-effects were noted in any of the three groups.Ondansetron, in this study of 90 children, was not very effective in preventing nausea and vomiting after neurosurgical operations.

Analyses of pesticide residues in fruit‐based baby food by liquid chromatography/electrospray ionization time‐of‐flight mass spectrometry

A liquid chromatography/electrospray ionization time-of-flight mass spectrometry (LC/ESI-TOFMS) method has been developed for the determination of 12 pesticides (namely, carbendazim, thiabendazole, imazalil, tridemorph, triadimefon, bitertanol, prochloraz, flutriafol, myclobutanil, iprodione, diphenylamine and procymidone) in fruit-based baby food (multi-fruit jars and juices intended for infant consumption). The developed method consists of a sample treatment step based on liquid-liquid extraction using acetonitrile, followed by a clean-up step based on dispersive solid-phase extraction (SPE) with a primary-secondary amine (PSA). Multi-fruit and apple juices were processed by a SPE procedure using Oasis HLB cartridges. Subsequent identification and quantitation was accomplished by LC/ESI-TOFMS analysis: the confirmation of the target pesticides was based on accurate mass measurements of selected ions (protonated molecules ([M+H]+) and fragment ions). Confirmation studies were accomplished at low concentration levels (10 microg kg-1) and accuracy errors lower than 2 ppm were obtained in most cases. Baby food extracts spiked at 10 microg kg-1 fortification level yielded average recoveries in the range 78-105% with relative standard deviations less than 10% for most of the analytes. Limits of detection (LODs) were between 0.1 and 4 microg kg-1 depending on the pesticide studied. Finally, the proposed method was applied to a total of 33 baby food samples from Spain and the United Kingdom. Although imazalil, thiabendazole and carbendazim were detected in a high number--over 60%- of baby food samples, none of the samples tested were found to be above the 0.01 mg kg-1 EU standard.

Barusiban suppresses oxytocin-induced preterm labour in non-human primates

BackgroundPreterm labour (PTL) is a major cause of neonatal mortality and morbidity, and oxytocin (OT) antagonists are potential tocolytics. Atosiban (TRACTOCILE) is a mixed vasopressin V1A/OT antagonist registered for acute treatment of PTL in Europe. Other off-label drugs have serious side effects. Barusiban is a selective OT antagonist which has reached clinical development. A monkey model with OT-induced PTL was developed to compare barusiban and atosiban. In addition, the feasibility for long-term treatment of PTL with barusiban was explored.MethodsConscious pregnant cynomolgus monkeys were monitored for intrauterine pressure (IUP). A sensor for IUP was implanted into the amniotic cavity, and biopotential sensors for electromyogram were attached to the uterus. For short-term experiments, individual low-dose OT infusions induced stable submaximal uterine contractions. Barusiban and atosiban were administered either as intravenous bolus or infusion at high or low doses. For long-term treatment, low-dose OT was infused daily for 3–6 hours to mimic PTL. In addition, continuous high-dose infusions of barusiban (150 μg kg-1 h-1) or fenoterol (3 μg kg-1 h-1) were administered.ResultsContractions of 15–40 mmHg were induced with individual OT infusions at 5–90 mU kg-1 h-1, and no OT-related desensitization occurred. Correlation was demonstrated between electromyograms and IUP curves. Barusiban was well tolerated and its potency was 4 times higher than atosiban's. Barusiban and atosiban demonstrated >95% efficacy. However, barusiban's duration of action was >13 hours (atosiban's 1–3 hours) and reversible with high-dose OT in emergency situations. OT control and fenoterol-treated monkeys delivered preterm (ca. day 154) and showed an increase in overall IUP. Barusiban-treated animals delivered normally following end of treatment (ca. day 163).ConclusionThe presented telemetry model provides an excellent method to evaluate PTL drug candidates. OT induced stable repetitive contractions and no desensitisation. Barusiban and atosiban demonstrated high efficacy and rapid onset of action. Barusiban, a selective OT antagonist has higher potency and prolonged duration of action than atosiban. Barusiban effectively suppressed IUP during daily OT-challenges, delayed labour, and prolonged monkeys' pregnancy till term.

Effects of Tolterodine on Afferent Neurotransmission in Normal and Resiniferatoxin Treated Conscious Rats

The beneficial effects of antimuscarinics on detrusor overactivity and overactive bladder syndrome are exerted during bladder filling, when there is no parasympathetic outflow from the spinal cord. We tested the hypothesis that, if tolterodine exerts some of its effects on afferent nerves, the functional elimination of C-fiber afferents should affect the actions of the drug on urodynamic parameters. The study was performed in normal female Sprague Dawley rats and rats treated with resiniferatoxin to eliminate vanilloid sensitive afferent nerves. Tolterodine was given intravenously to normal and resiniferatoxin treated animals. To test if tolterodine at the doses used affects efferent neurotransmission the drug was given to normal and resiniferatoxin treated animals in which detrusor activity was induced by apomorphine. In resiniferatoxin treated animals (0.3 mg kg-1 subcutaneously) the mean micturition interval and volume, and mean residual volume increased significantly compared to those in controls. Baseline and micturition pressures in control and resiniferatoxin treated animals were similar, whereas threshold pressures were higher in resiniferatoxin treated animals. In controls 10 microg kg-1 tolterodine administered intravenously increased the mean micturition interval, bladder capacity and micturition volume. In resiniferatoxin treated rats 1 and 10 microg kg-1 tolterodine increased the mean micturition interval, bladder capacity and micturition volume. Subcutaneous administration of 100 microg kg-1 apomorphine induced detrusor overactivity in all rats. The AUC of intravesical pressure during the initial 10 minutes from the start of detrusor overactivity showed no difference between normal and resiniferatoxin treated rats with or without tolterodine pretreatment. Tolterodine increased the micturition interval and bladder capacity in controls and in resiniferatoxin treated animals, suggesting that these effects were exerted independently of resiniferatoxin sensitive afferents. Tolterodine did not decrease the contractile effects of apomorphine at the doses used, suggesting that the drug had no effect on efferent neurotransmission during voiding.

Effect of midazolam, dexamethasone and their combination on the prevention of nausea and vomiting following strabismus repair in children

Postoperative nausea and vomiting is a common complication following strabismus surgery. This randomized and double-blind study was designed to evaluate the efficacy of midazolam alone or in combination with dexamethasone in reducing the incidence of postoperative nausea and vomiting in children undergoing strabismus repair. One hundred ASA I children, aged 4-12 yr, scheduled to undergo elective strabismus surgery, were enrolled. No premedication was given. Anaesthesia was induced with sevoflurane, nitrous oxide and oxygen. After induction, fentanyl 2 microg kg-1 and cisatracurium 0.1 mg kg-1 were administered and an endotracheal tube was inserted. After induction of anaesthesia and before start of surgery, patients were randomly allocated into one of four groups of 25 children each to receive placebo, midazolam 50 microg kg-1, dexamethasone 0.5 mg kg-1 or a combination of midazolam 50 microg kg-1 and dexamethasone 0.5 mg kg-1. Episodes of nausea, and retching and vomiting were recorded during the first 24 h after surgery. The incidence of postoperative nausea was 48%, 32%, 12% and 0% with placebo, dexamethasone, midazolam and the midazolam-dexamethasone combination, respectively. The incidence of vomiting was 52% and 32% with placebo and dexamethasone, respectively; no child vomited with midazolam alone, or with the midazolam-dexamethasone combination. Prophylactic midazolam with or without dexamethasone reduces the incidence of PONV in children undergoing strabismus repair.

Oral clonidine vs midazolam in the prevention of sevoflurane-induced agitation in children. A prospective, randomized, controlled trial

This randomized, double-blind study tested the hypothesis that, in comparison with midazolam, premedication with oral clonidine reduces the incidence of emergence agitation in preschool children anaesthetized with sevoflurane. Sixty-eight ASA I-II children undergoing circumcision were randomized into three groups to receive different oral premedication given 30 min before anaesthesia: midazolam 0.5 mg kg-1, clonidine 2 microg kg-1, and clonidine 4 microg kg-1. Sevoflurane anaesthesia was administered via a facemask (O2/N2O: 40/60). Analgesia was with penile block (bupivacaine 0.5% 0.3 ml kg-1) and rectal paracetamol (30 mg kg-1). During the first postoperative hour, children were evaluated using a modified 'objective pain scale'. Only the 4 microg kg-1 dose of clonidine was associated with a significant reduction in emergence agitation. Fewer children in the clonidine 4 microg kg-1 group displayed agitation (25%) than in the midazolam group (60%) (P=0.025). Incidence of hypotension and bradycardia, time to first micturition and first drink did not differ among groups. In comparison with midazolam, clonidine 4 microg kg-1 reduced sevoflurane-induced emergence agitation without increasing postoperative side-effects.

Multicentre evaluation of the adenosine agonist GR79236X in patients with dental pain after third molar extraction

Adenosine is analgesic in humans, and the selective adenosine A1 receptor agonist GR79236X has significant anti-nociceptive activity in an animal pain model of inflammatory pain. Seventy-nine patients with moderate pain after third molar extraction under general anaesthesia were randomized to receive a 15 min double-blind infusion containing either GR79236X 4 microg kg-1, GR79236X 10 microg kg-1, diclofenac 50 mg, or saline placebo. Rescue analgesia was promptly available to all patients. Meaningful pain relief (mild or no pain) was attained by 9 (47%) patients in the placebo group, 12 (63%) patients in the GR79236 4 microg kg-1 group, 10 (48%) patients in the 10 microg kg-1 group, and 16 (80%) patients in the diclofenac 50 mg group. Neither dose of GR79236 produced a significant improvement over placebo, but diclofenac was superior to both placebo (P=0.036) and GR79236 10 microg kg-1 (P=0.034). Median times to rescue or additional analgesia were 62, 100, 60, and 363 min for patients receiving placebo, GR79236 4 microg kg-1, 10 microg kg-1, and diclofenac 50 mg, respectively (diclofenac significantly longer than placebo, P=0.002 log-rank test). Pain control was poor in the placebo group and in both GR79236 groups, with between 79 and 86% of patients having good pain control (i.e. mild or no pain) for <20% of the time compared with only 30% of patients who received diclofenac. We found no evidence of efficacy of GR79236 compared with placebo, but the active control diclofenac was effective. It is possible that a higher dose of GR79236 might have been effective or that i.v. administration of this drug does not achieve appropriate concentrations in the brain or peripheral nerves.

Dose of alfentanil needed to obtain optimal intubation conditions during rapid-sequence induction of anaesthesia with thiopentone and rocuronium

The primary aim of the present study was to determine the dose of alfentanil that must be added to a rapid-sequence induction (RSI) regimen using thiopentone and rocuronium to obtain optimal intubation conditions in >95% of the individuals. A total of 60 ASA I patients were randomly allocated to five different alfentanil dose groups (0, 15, 30, 45, or 60 microg kg-1). A blinded dose of alfentanil followed by thiopentone 4 mg kg-1 and rocuronium 1 mg kg-1 was administered in rapid succession, and tracheal intubation was attempted 40 s thereafter. The relationship between the alfentanil dose and the probability of optimal intubation conditions was determined by non-linear logistic regression analysis. Blood pressure (BP) changes were recorded continuously using an intra-arterial catheter. The success rate of optimal intubation conditions increased with increasing doses of alfentanil. The alfentanil dose needed to obtain optimal intubation conditions in >95% of the patients was 36.4 (CI 33.4-39.4) microg kg-1. In 12 patients, the systolic BP declined to <90 mm Hg during the 3 min immediately after intubation. Adding 36-40 microg kg-1 alfentanil to a regimen of thiopentone and rocuronium during RSI of anaesthesia may significantly increase the success rate of optimal intubation conditions. Significant hypotension requiring vasopressor treatment may occur.

Low-dose remifentanil to suppress haemodynamic responses to noxious stimuli in cardiac surgery: a dose-finding study

High-dose remifentanil (1-5 microg kg-1 min-1), commonly used for cardiac surgery, has been associated with muscle rigidity, hypotension, bradycardia, and reduced cardiac output. The aim of this study was to determine an optimal lower remifentanil dose, which should be accompanied by fewer adverse events, that still effectively suppresses haemodynamic responses to typical stressful stimuli (i.e. intubation, skin incision, and sternotomy). Total i.v. anaesthesia consisted of a target-controlled propofol (2 microg ml-1) and a remifentanil infusion. Forty patients were allocated to receive either a constant infusion of remifentanil at 0.1 microg kg-1 min-1 or up-titrations to 0.2, 0.3, or 0.4 microg kg-1 min-1, respectively, 5 min before each stimulus. Subsequently, changes in heart rate and mean arterial blood pressure were recorded for 8 min. Increases exceeding 20% of baseline were considered to be of clinical relevance. Patients who exhibited these alterations were termed responders. The number of responders was less with the two higher remifentanil dosages (P<0.05) while propofol target doses could either be kept at the same level or even be reduced without affecting the plane of anaesthesia. Although single phenylephrine bolus had to be applied more frequently in these two groups (P<0.05), no severe haemodynamic depression was observed. Remifentanil at 0.3 and 0.4 microg kg-1 min-1 in combination with a target-controlled propofol infusion in the pre-bypass period is well tolerated. It appears to mitigate potentially hazardous haemodynamic responses from stressful stimuli equally well as higher doses when compared with data from the literature.

Molecularly imprinted polymer solid-phase extraction coupled to square wave voltammetry at carbon fibre microelectrodes for the determination of fenbendazole in beef liver

A molecularly imprinted polymer was developed and used for solid-phase extraction (MISPE) of the antihelmintic fenbendazole in beef liver samples. Detection of the analyte was accomplished using square wave voltammetry (SWV) at a cylindrical carbon fibre microelectrode (CFME). A mixture of MeOH/HAc (9:1) was employed both as eluent in the MISPE system and as working medium for electrochemical detection of fenbendazole. The limit of detection was 1.9x10(-7) mol L-1 (57 microg L-1), which was appropriate for the determination of fenbendazole at the maximum residue level permitted by the European Commission (500 microg kg-1 in liver). Given that the SW voltammetric analysis could not be directly performed in the sample extract as a consequence of interference from some sample components, a sample clean-up with a MIP for selectively retaining fenbendazole was performed. The MIP was synthesized using a 1:8:22 template/methacrylic acid/ethylene glycol dimethacrylate ratio. A Britton-Robinson Buffer of pH 9.0 was selected for retaining fenbendazole in the MIP cartridges, and an eluent volume of 5.0 mL at a flow rate of 2.0 mL min-1 was chosen in the elution step. Cross-reactivity with the MIP was observed for other benzimidazoles. The synthesized MIP exhibited a good selectivity for benzimidazoles with respect to other veterinary drugs. The applicability of the MISPE-SWV method was tested with beef liver samples, spiked with fenbendazole at 5,000 and 500 microg kg-1. Results obtained for ten different liver samples yielded mean recoveries of (95+/-12)% and (96+/-11)% for the upper and lower concentration level, respectively.

Development of an Enzyme-Linked Immunosorbent Assay for Seven Sulfonamide Residues and Investigation of Matrix Effects from Different Food Samples

Direct competitive enzyme-linked immunosorbent assays (ELISA) were developed to detect a broad range of sulfonamides in various matrices. Screening for this class of antibiotics in pig muscle, chicken muscle, fish, and egg extracts was accomplished by simple, rapid extraction methods carried out with only phosphate-buffered saline (PBS) buffer. Twenty milliliters of extract solution was added to 4 g of sample to extract the sulfonamide residues, and sample extracts diluted with assay buffer were directly analyzed by ELISA; matrix effects could be avoided with 1:5 dilution of pig muscle, chicken muscle, and egg extracts with PBS and 1:5 dilution of fish extract with 1% bovine serum albumin (BSA)-PBS. For liver sample, the extraction method was a little more complicated; 2 g of sample was added to 20 mL of ethanol, mixed, and then centrifuged. The solvent of 10 mL of the upper liquid was removed, and the residues were dissolved in 10 mL of PBS and then filtered; the filtrate was diluted two-fold with 0.5% BSA-PBS for ELISA. These common methods were able to detect seven sulfonamide residues such as sulfisozole, sulfathiazole, sufameter, sulfamethoxypyridazine, sulfapyridine, sulfamethizole, and sulfachlorpyridazine in pig muscle, liver, chicken muscle, egg, and fish. The assay's detection limits for these compounds were less than 100 microg kg-1. Various extraction methods were tested, and the average recovery (n=3) of 100 microg kg-1 for the matrices was found to range from 77.3 to 123.7%.

Estimating left ventricular contractility using inspiratory-hold maneuvers

To compare estimates of left ventricular (LV) end-systolic elastance created by inferior vena caval (IVC) occlusion with those by apneic continuous positive airway pressure (CPAP). Prospective interventional study in a university large animal research laboratory. Sixteen intact, pentobarbital-anesthetized mongrel male dogs. Insertion of LV conductance and pressure catheters, then during apnea sequentially performed IVC occlusion and CPAP of 5, 10, and 15 mmHg for 10 s, each interspersed by positive-pressure breathing. In the final 11 dogs runs were repeated during both esmolol (2 mg min-1) and dobutamine (5 microg kg-1 min-1) infusions. LV pressure-volume relationships during apneic baseline and then as LV end-diastolic volume decreased by each maneuver to calculate LV end-systolic elastance and preload-recruitable stroke work as measures of contractility. End-systolic elastance estimated at 5 mmHg CPAP levels and IVC occlusions were similar while 10 and 15 mmHg CPAP gave different values. However, end-systolic elastance was lower during esmolol infusion and higher during dobutamine for all CPAP and IVC occlusion maneuvers. Preload-recruitable stroke work measures were similar across maneuvers. With increasing CPAP the LV filling and end-systolic elastance were progressively shifted upward and to the left, with volume on the x-axis, consistent with an unaccounted for increase in intrathoracic pressure. The use of 5 mmHg CPAP-induced preload-reduction allows estimation of LV end-systolic elastance and preload-recruitable stroke work in intact dogs. Increasing CPAP to more than 10 mmHg creates estimates of LV contractility that are different but covary with IVC occlusion-derived values.

Effect of intraoperative intravenous acetaminophen vs. intramuscular meperidine on pain and discharge time after paediatric dental restoration

Enteral acetaminophen (paracetamol) has limited analgesic efficacy due to its delayed absorption and sub-therapeutic plasma concentration. Intravenous (i.v.) acetaminophen solves this issue and could thus provide adequate analgesia as a single agent. We compared intraoperative i.v. acetaminophen with intramuscular (i.m.) meperidine with regard to postoperative analgesia and readiness for discharge in paediatric patients undergoing day care dental restoration. Forty children were randomized, in this double-blind study, to receive acetaminophen 15 mg kg-1 i.v. (Group A) or meperidine 1 mg kg-1 i.m. (Group M) after anaesthesia induction and before surgery. All patients received midazolam 0.5 mg kg-1 orally 30 min preoperatively and fentanyl 1 microg kg-1 i.v. immediately after induction. Anaesthesia was induced with either sevoflurane inhalation or propofol 3 mg kg-1 i.v. and was maintained with sevoflurane. Postoperatively, the objective pain scale, Ramsay sedation score, and Aldrete score were determined every 5 min until readiness for recovery room discharge (defined as achieving an Aldrete score of 10). Group A had slightly higher pain scores during early recovery compared with Group M (estimated marginal means: 3 +/- SEM 0.4 vs. 2 +/- SEM 0.4, respectively (95% CI for difference: 0.4, 2.6), P = 0.012 for F-test). In contrast, Ramsay scores were higher in Group M than in Group A during assessment period (estimated marginal means: 4 +/- SEM 0.3 vs. 2 +/- SEM 0.4, respectively (95% CI for difference: -2.3, -0.3), P = 0.013 for F-test). Group A patients achieved an Aldrete score of 10 sooner than those in Group M (5 +/- SEM 2 vs. 16 +/- SEM 4 min, respectively (95% CI for difference: -9, -14), P = 0.009). Compared with i.m. meperidine, intraoperative i.v. acetaminophen resulted in slightly higher pain scores but earlier readiness for recovery room discharge in paediatric patients undergoing dental restoration. The potential economic benefit of early recovery room discharge needs to be further explored.

A comparison of the effect on gastric emptying of propofol or dexmedetomidine in critically ill patients

Propofol and dexmedetomidine are widely used for sedation in the intensive care unit yet there are limited data on its effects on gastric motility. In our preliminary study, we examined whether or not any effect of propofol and dexmedetomidine on gastric emptying is preserved in critically ill patients. Twenty-four critically ill, enterally fed adult patients each received enteral feeding via a nasogastric tube at 50 mL h-1 throughout the 5-h study period. Either propofol 2 mg kg-1 h-1 (n = 12, Group P) or dexmedetomidine 0.2 microg kg-1 h- (n = 12, Group D) was given intravenously over 5 h. Gastric motility was measured indirectly by analysis of the absorption over time of 1.5 g of paracetamol administered into the stomach at the start of the study period. At the beginning and end of the study, residual gastric volume and pH of residual gastric fluid were measured. Gastric residual volume measured at the end of propofol infusion (19.33 +/- 11.33) was found to be higher when compared with the volume measured before infusion (11.33 +/- 4.84) and after dexmedetomidine infusion (9.17 +/- 4.54). But, there was no difference between groups in gastric emptying time (AUC120 894.53 +/- 499.39 vs. 1113.46 +/- 598.09 propofol and dexmedetomidine groups, respectively). In our study, gastric residual volume measured at the end of propofol infusion was found to be higher when compared with the volume measured before infusion and after dexmedetomidine infusion. There was no difference between groups in gastric emptying time.

Reflex activity caused by laryngoscopy and intubation is obtunded differently by meptazinol, nalbuphine and fentanyl

To evaluate the different potencies of several opioids in obtunding reflex mechanisms of laryngoscopy and intubation. Three groups of patients (each n = 25, ASA 1-2) undergoing elective plastic surgery were randomly given meptazinol (2.5 mg kg-1), nalbuphine (0.3 mg kg-1) or fentanyl (5 microg kg-1) in a blinded fashion prior to laryngoscopy and intubation. This was followed by a standardized bolus induction of a barbiturate and a muscle relaxant. The response to laryngoscopy and intubation was studied, using blood pressure, heart rate and bispectral index. With fentanyl, there was an increase of heart rate by 17%, and systolic blood pressure by 7% when compared to control. Bispectral index dropped an additional 8% when compared to 1 min after barbiturate induction. In the nalbuphine group there was a 16% increase in systolic blood pressure, and a 16% increase in heart rate when compared to control. Also, bispectral index increased by 18% when compared to 1 min after barbiturate injection. The group receiving meptazinol demonstrated no cardiovascular changes although bispectral index dropped by an additional 19% when compared to 1 min after barbiturate injection. Meptazinol, appears to depress cardiovascular stimulatory effects and electroencephalogram arousal induced by laryngoscopy and intubation better than nalbuphine or fentanyl.