Pulmonary Disposition of Propofol in Surgical Patients

2000 ◽  
Vol 93 (4) ◽  
pp. 986-991 ◽  
Author(s):  
Yan-Ling He ◽  
Hiroshi Ueyama ◽  
Chikara Tashiro ◽  
Takashi Mashimo ◽  
Ikuto Yoshiya
Keyword(s):  
Plasma Concentrations ◽  
Area Under The Curve ◽  
Back Diffusion ◽  
Blood Samples ◽  
Arterial Blood ◽  
Pulmonary Uptake ◽  
Human Lungs ◽  
Infusion Study ◽  
Significant Difference ◽  
First Pass

Background The lungs have been mentioned as a possible site contributing to the extrahepatic clearance of propofol. The objective of the present study was to clarify the pulmonary disposition of propofol directly in human lungs by investigating both the first-pass uptake and pulmonary extraction at pseudo-steady state. Methods Nine patients were enrolled in the first-pass uptake study. Propofol (5 mg) and indocyanine green (ICG; 15 mg) were simultaneously administered via a central venous catheter within 1 s, and sequential arterial blood samples were obtained from the radial artery at 1-s intervals up to 45 s. Eleven patients were included in the infusion study, and propofol was infused via the jugular vein at a rate of 50 microgram. kg-1. min-1. Blood samples were simultaneously collected from pulmonary and radial arteries up to 60 min. Results A pronounced difference in the dilution curves between propofol and ICG was observed, and 28.4 +/- 11.6% (mean +/- SD) of propofol was taken up during the single passage through the human lung. The mean pulmonary transit time of propofol (31.3 +/- 6.0 s) was significantly longer than that of ICG (22.4 +/- 2.7 s; P < 0.01), indicating that some of the propofol trapped by lungs returned to the circulation by back diffusion. In the constant infusion study, no significant differences were observed with the plasma concentrations of propofol between pulmonary and radial arteries except for that at 2 min. The area under the curve of pulmonary and radial arterial concentration curves to 60 min were 59.1 +/- 14.8 and 56.8 +/- 12.5 microg. ml-1. min-1, respectively. No significant difference was observed with the area under the curve, suggesting that metabolism was not involved in the pulmonary uptake in human lungs. Conclusions Most of the propofol that undergoes pulmonary uptake during the first pass was released back to the circulation by back diffusion. Metabolism was not involved in the pulmonary uptake in human lungs.

P1315PREDICTABILITY OF SONOGRAPHICALLY DETERMINED IMMEDIATE POST-OPERATIVE BLOODFLOW AND VEIN DIAMETER ON PRIMARY RADIOCEPHALIC FISTULA SHORT AND LONGTERM OUTCOMES

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Claude Renaud ◽  
Desmond Ooi ◽  
Chuo Ren Leong
Keyword(s):  
Predictive Value ◽  
Cox Regression ◽  
Area Under The Curve ◽  
Primary Patency ◽  
Arterial Blood Flow ◽  
Secondary Patency ◽  
Arterial Blood ◽  
Linear Probe ◽  
Significant Difference ◽  
Esrd Patients

Abstract Background and Aims Vascular access (VA) guidelines recommend radio-cephalic (RC) over upper arm autogenous arteriovenous fistulas (AVF) as first line VA for hemodialysis in end stage renal disease (ESRD) patients. RCAVFs generally have inferior maturation and patency rates predicated on a lower feeding arterial blood flow (BF) and outflow vein calibre (VC). However studies on postoperative BF and VC as predictors of AVF outcomes, so far are confounded by their focus on early outcomes only, heterogeneity of AVFs studied, variable timing of assessment and use of non-standardised outcome definitions. Our aim was therefore to assess the accuracy and influence of immediate post-operative BF and VC on both early and longterm outcomes in a homogenous cohort of primary RCAVFs using standardised definitions and outcome measures as mandated by VA guidelines. Method This was a prospective study conducted in multi-ethnic Asian ESRD patients who had their primary RCAVFs created between October 2013 and October 2014 under regional anesthesia at Khoo Teck Puat hospital Singapore. All AVFs were assessed immediately after surgery for brachial artery BF and outflow VC using doppler ultrasound. A 10MHz linear probe and GE Logic e R7 machine were used exclusively by a single operator. Receiver operating characteristic (ROC) curves were generated to determine the optimal BF and VC cut-off for AVF maturation. Maturation was defined as BF>600mL/min, VC>6mm and vein depth <6mm at 6 weeks post-op. An area under the curve (AUC)> 0.7 was considered clinically significant. Kaplan–Meier analysis was used to evaluate the AVF primary and secondary patency based on best BF and VC cut-offs. Cox regression statistics was used to determine AVF hazard factors. Results Fifty-seven primary RCAVFs were created and included in the study. The baseline characteristics are shown in Table 1. Sonography- based non-assisted maturation at 6 weeks was 56%. ROC identified 410 mL/min and 42mm as the best BF and VC cut-off respectively to most accurately predict 6-week maturation. The sensitivity, specificity, positive predictive value and negative predictive value were 75%, 61%, 44% and 86% for BF at 410 mL/min and 69%, 61%, 41% and 83% for VC at 42mm respectively. Survival analysis (Fig. 1 and 2) showed that AVFs with VC≥42 mm compared to <42mm had significantly greater 6 months, 1-year, 2-year and 4-year primary and secondary patency rates. There was no significant difference in patency rates between AVFs with BF≥410 and <410mL/min. Cox proportional regression hazard analysis showed that diabetes (HR 2.26, CI 1.02-4.99, p= 0.04) and maturation (HR 0.47, 95% CJ 0.24-0.89, p=0.02) as significant contributed to the variability of primary patency. Only VC (HR 0.28, 95% CI 0.13-0.063, p=0.002) impacted significantly towards secondary patency. Conclusion An immediate post-op BF≥410mL/min and VC≥42mm can predict early RCAVF outcome in the form of nonassisted maturation, but only VC accurately impact on longterm AVF survival. VA surveillance efforts should therefore target RCAVFs with post-op VC <42mm for timely intervention and maintenance of longterm patency.

The Pulmonary First-pass Uptake of Five Nondepolarizing Muscle Relaxants in the Pig 

1999 ◽  
Vol 90 (2) ◽  
pp. 477-483 ◽  
Author(s):  
Ton M. Beaufort ◽  
Johannes H. Proost ◽  
Martin C. Houwertjes ◽  
Jan Roggeveld ◽  
Mark J.K. H. Wierda
Keyword(s):  
Mean Transit Time ◽  
Onset Time ◽  
Muscle Relaxants ◽  
Arterial Blood ◽  
Tibialis Muscle ◽  
Pulmonary Uptake ◽  
Org 9487 ◽  
First Pass ◽  
The Right ◽  
Org 7617

Background It is not known whether the lungs influence the early pharmacokinetics of muscle relaxants and, if they do, whether differences in pulmonary uptake contribute to the differences in potency and/or onset time among muscle relaxants. Because the lungs are uniquely positioned, receive the entire cardiac output, have a large capillary surface area, and can temporarily store various basic drugs, the authors determined whether substantial pulmonary first-pass uptake of muscle relaxants occurs. Methods In 14 pigs, rocuronium, vecuronium, Org 9487, Org 7617, or d-tubocurarine were administered simultaneously with indocyanin green within 1 s into the right ventricle, and then arterial blood was sampled every 1.2 s (in the first min). The tibialis muscle response was registered mechanomyographically. Results The maximum block was 93% (68-100% [median and range]). Onset times ranged from 83 s (78-86 s) for rocuronium to 182 s (172-192 s) for d-tubocurarine. Fraction-versus-time outflow curves showed that the peak of muscle relaxants and indocyanin green occurred almost simultaneously. Pulmonary first-pass retention was negligible. The retention of muscle relaxants at 95% passage of indocyanin green was -9% (-31 to 18%). The difference in the mean transit time between muscle relaxant and indocyanin green was 1.0 (0.8 to 1.4), 0.2 (-0.8 to 0.3), 0.3 (0.2 to 0.4), 0.5 (0.2 to 1.3), and -2.2 s for rocuronium, vecuronium, Org 9487, Org 7617, and d-tubocurarine, respectively. Conclusions There is no substantial pulmonary first-pass uptake of rocuronium, vecuronium, Org 9487, Org 7617, or d-tubocurarine in pigs. Therefore, differences in pulmonary first-pass uptake do not contribute to the differences in potency and/or onset time among muscle relaxants.

scholarly journals The feeding route (enteral or parenteral) affects the plasma response of the dipetide Ala-Gln and the amino acids glutamine, citrulline and arginine, with the administration of Ala-Gln in preoperative patients

2005 ◽  
Vol 94 (1) ◽  
pp. 19-26 ◽  
Author(s):  
Gerdien C. Melis ◽  
Petra G. Boelens ◽  
Joost R. M. van der Sijp ◽  
Theodora Popovici ◽  
Jean-Pascal De Bandt ◽  
...  
Keyword(s):  
Amino Acids ◽  
Plasma Levels ◽  
Plasma Concentrations ◽  
High Availability ◽  
Blood Samples ◽  
Arterial Blood ◽  
Plasma Response ◽  
Enteral Administration ◽  
Plasma Arginine ◽  
Arginine Concentration

Enhancement of depressed plasma concentrations of glutamine and arginine is associated with better clinical outcome. Supplementation of glutamine might be a way to provide the patient with glutamine, and also arginine, because glutamine provides the kidney with citrulline, from which the kidney produces arginine when plasma levels of arginine are low. The aim of the present study was to investigate the parenteral and enteral response of the administered dipeptide Ala-Gln, glutamine, citrulline and arginine. Therefore, seven patients received 20 g Ala-Gln, administered over 4 h, parenterally or enterally, on two separate occasions. Arterial blood samples were taken before and during the administration of Ala-Gln. ANOVA and a pairedttest were used to test differences (P<0·05). Ala-Gln was undetectable with enteral administration, whereas Ala-Gln remained stable at a plasma concentration of 268 μmol/l throughout parenteral infusion and rapidly decreased towards zero after infusion was stopped. The highest level of glutamine was observed with parenteral infusion of the dipeptide, although enteral infusion also significantly increased plasma levels of glutamine. The highest plasma response of citrulline was observed with the enteral administration of the dipeptide, although parenteral administration also increased plasma levels of citrulline. Plasma arginine increased significantly with parenteral infusion, but not with enteral administration of Ala-Gln. In conclusion, administrations of Ala-Gln, parenteral or enteral, resulted in an increased plasma glutamine response, as compared with baseline. Interestingly, in spite of the high availability of citrulline with enteral administration of the dipeptide, only parenteral infusion of Ala-Gln increased plasma arginine concentration.

Charge-Affected Transperitoneal Movement of Amino Acids in Capd

1996 ◽  
Vol 16 (1_suppl) ◽  
pp. 88-90 ◽  
Author(s):  
Toshiyuki Nakao ◽  
Makoto Ogura ◽  
Hajime Takahashi ◽  
Tomonari Okada
Keyword(s):  
Amino Acids ◽  
Molecular Weight ◽  
Dwell Time ◽  
Plasma Concentrations ◽  
University Hospital ◽  
Blood Samples ◽  
Significant Difference ◽  
Molecular Charge ◽  
Solute Movement ◽  
Positively Charged

Our objective was to investigate the influence of molecular charge on transperitoneal solute movement in continuous ambulatory peritoneal dialysis (CAPD). Tests of peritoneal equilibration were performed. Two liters of 2.27% or 2.5% glucose CAPD dialysate were infused and the dialysate samples were taken after 2 hr and 4 hr, and blood samples were obtained after 4-hr dwell time. Dialysate-to-plasma concentrations ratios (DIP) were calculated for creatinine (Cr) and three amino acids with almost the same molecular weight but quite different charges: glutamic acids (Glu: negatively charged), glutamine (Gin: near neutrally charged), and lysine (Lys: positively charged). The setting was a university hospital. There were 23 stable CAPD patients with a mean age of 56.5±9.5 years and a mean CAPD duration of 15.2±19.4 months. DIP ratio of Glu was much lower than those of Gin, Lys and Cr at both 2 hr and 4 hr (p < 0.01), and DIP of Lys was significantly lower than that of Gin (p < 0.01). There was no significant difference of DIP between Gin and Cr. The order of transperitoneal mobility among the three amino acids was Gin > Lys > Glu. Transperitoneal movement of solutes in CAPD is influenced by molecular charge, the movement of negatively charged solutes is most remarkably retarded in cases of amino acids.

Pharmacokinetic comparison of two buprenorphine formulations after buccal administration in healthy male cats

2017 ◽  
Vol 20 (4) ◽  
pp. 312-318 ◽  
Author(s):  
Brett M Gulledge ◽  
Kristen M Messenger ◽  
Karen K Cornell ◽  
Heather Lindell ◽  
Chad W Schmiedt
Keyword(s):  
Liquid Chromatography ◽  
Maximum Concentration ◽  
High Performance ◽  
Plasma Concentrations ◽  
Area Under The Curve ◽  
Storage Condition ◽  
Healthy Male ◽  
Limit Of Quantification ◽  
Significant Difference ◽  
Extent Of Absorption

Objectives The objective of this study was to compare the pharmacokinetics of compounded and commercially available aqueous formulations of buprenorphine after a single buccal dose to healthy cats and to evaluate the concentrations of a compounded buprenorphine solution over 21 days when stored at room temperature (RT; 22–24°C) with exposure to light or when refrigerated at 4°C while protected from light. Methods Six young healthy male cats were administered single buccal doses of compounded and commercially available formulations of buprenorphine (0.03 mg/kg) using a randomized, blinded, two-period crossover design. Blood samples were obtained over a 24 h period and plasma buprenorphine concentrations were determined using ultra-high-pressure liquid chromatography with mass spectrometry detection. Three batches of the compounded formulation were stored at RT or 4°C and aliquots were evaluated over 21 days for buprenorphine concentration using high-performance liquid chromatography with fluorescence detection. Results Plasma concentrations of buprenorphine were above the limit of quantification up to 6 h in some cats and up to 3 h in all cats. The area under the curve was significantly less for the compounded formulation ( P = 0.004). A significant difference was not detected between formulations for time to maximum concentration ( P = 0.11), maximum concentration ( P = 0.06), half-life ( P = 0.88) and mean residence time ( P = 0.57). Buprenorphine concentration in the compounded formulation was not affected by storage condition or time and remained between 90% and 110% of the target concentration at all time points. Conclusions and relevance A buprenorphine solution prepared from sublingual tablets is absorbed after buccal administration in healthy cats. The extent of absorption is significantly less than that of the commercially available formulation. The compounded solution maintains an acceptable buprenorphine concentration for at least 21 days when stored at RT or refrigerated.

Glucuronidation and its effect on the bioactivity of amentoflavone, a biflavonoid from Ginkgo biloba leaves

2020 ◽  
Author(s):  
Lili Gan ◽  
Jiating Ma ◽  
Guoquan You ◽  
Jinxia Mai ◽  
Zhaoyu Wang ◽  
...  
Keyword(s):  
Antioxidant Activity ◽  
Anticancer Activity ◽  
Ginkgo Biloba ◽  
Metabolic Profile ◽  
Plasma Concentrations ◽  
Area Under The Curve ◽  
Pharmacokinetic Studies ◽  
Significant Difference ◽  
Dietary Flavonoid ◽  
U251 Cells

Abstract Objectives Ginkgo biloba leaves contain amentoflavone (AMF), a dietary flavonoid that possesses antioxidant and anticancer activity. Flavonoids are extensively subjected to glucuronidation. This study aimed to determine the metabolic profile of AMF and the effect of glucuronidation on AMF bioactivity. Methods A pharmacokinetic study was conducted to determine the plasma concentrations of AMF and its metabolites. The metabolic profile of AMF was elucidated using different species of microsomes. The antioxidant activity of AMF metabolites was determined using DPPH/ABTS radical and nitric oxide assays. The anticancer activity of AMF metabolites was evaluated in U87MG/U251 cells. Key findings Pharmacokinetic studies indicated that the oral bioavailability of AMF was 0.06 ± 0.04%, and the area under the curve of the glucuronidated AMF metabolites (410.938 ± 62.219 ng/ml h) was significantly higher than that of AMF (194.509 ± 16.915 ng/ml h). UGT1A1 and UGT1A3 greatly metabolized AMF. No significant difference was observed in the antioxidant activity between AMF and its metabolites. The anticancer activity of AMF metabolites significantly decreased. Conclusions A low AMF bioavailability was due to extensive glucuronidation, which was mediated by UGT1A1 and UGT1A3. Glucuronidated AMF metabolites had the same antioxidant but had a lower anticancer activity than that of AMF.

First-pass Lung Uptake and Pulmonary Clearance of Propofol 

1999 ◽  
Vol 91 (6) ◽  
pp. 1780-1780 ◽  
Author(s):  
Jette A. Kuipers ◽  
Fred Boer ◽  
Wim Olieman ◽  
Anton G. L. Burm ◽  
James G. Bovill
Keyword(s):  
Pulmonary Tissue ◽  
Tissue Compartment ◽  
Arterial Blood ◽  
Concentration Time ◽  
Pulmonary Uptake ◽  
First Pass ◽  
Recirculatory Model ◽  
Pass Through ◽  
The Right ◽  
Kinetics Of

Background The principal site for elimination of propofol is the liver. The clearance of propofol exceeds hepatic blood flow; therefore, extrahepatic clearance is thought to contribute to its elimination. This study examined the pulmonary kinetics of propofol using part of an indocyanine green (ICG) recirculatory model. Methods Ten sheep, immobilized in a hammock, received injections of propofol (4 mg/kg) and ICG (25 mg) via two semipermanent catheters in the right internal jugular vein. Arterial blood samples were obtained from the carotid artery. The ICG injection was given for measurement of intravascular recirculatory parameters and determination of differences in propofol and ICG concentration-time profiles. No other medication was given during the experiment, and the sheep were not intubated. The arterial concentration-time curves of ICG were analyzed with a recirculatory model. The pulmonary uptake and elimination of propofol was analyzed with the central part of that model extended with a pulmonary tissue compartment allowing elimination from that compartment. Results During the experiment, cardiac output was 3.90+/-0.72 l/min (mean +/- SD). The blood volume in heart and lungs, measured with ICG, was 0.66+/-0.07 l. A pulmonary tissue compartment of 0.47+/-0.16 l was found for propofol. The pulmonary first-pass elimination of propofol was 1.14+/-0.23 l/min. Thirty percent of the dose was eliminated during the first pass through the lungs. Conclusions Recirculatory modeling of ICG allows modeling of the first-pass pulmonary kinetics of propofol concurrently. Propofol undergoes extensive uptake and first-pass elimination in the lungs.

scholarly journals Effects of Endotracheal Administration of Epinephrine in Cardiac Arrest of Adult and Pediatric Swine

2019 ◽  
Vol 3 (2) ◽  
pp. p34
Author(s):  
Steven Kertes ◽  
Valentina Fillman ◽  
Brandon Krawczyk ◽  
Logan Hirsch ◽  
Allison Martin ◽  
...  
Keyword(s):  
Cardiac Arrest ◽  
Area Under The Curve ◽  
Spontaneous Circulation ◽  
Average Weight ◽  
Male Adult ◽  
Epinephrine Administration ◽  
Blood Samples ◽  
Return Of Spontaneous Circulation ◽  
Significant Difference ◽  
Adults And Children

BACKGROUND: Few studies have investigated the effects of hypovolemia on area under the curve (AUC) and the return of spontaneous circulation (ROSC) comparing adults and children in cardiac arrest.AIMS: To compare the epinephrine endotracheal (ET) administration relative to AUC, rate, time to, and odds of achieving ROSC between hypovolemic adult and pediatric cardiac arrest models.METHODS: This was an experimental study using male Adult ET and Pediatric ET swine. Pediatric ET pigs (N=7) weighed 20-30 kg representing the average weight for a child between 5 and 6 years of age. Adult ET pigs (N=7) weighed 60 to 80 kg. All were exsanguinated 35% of their blood volume. Swine were put into arrest for 2 minutes. Cardiopulmonary resuscitation (CPR) was initiated for 2 minutes; epinephrine was then administered. Blood samples were collected over 5 minutes. RESULTS: No significant difference occurred in AUC between the groups (p > 0.05). The Pediatric ET group had higher rates of ROSC and a shorter time to ROSC (p < 0.05). Pediatric ET group had a 15 times greater odds of achieving ROSC compared to the Adult ET group. CONCLUSION: Based on the results of this study, we recommend epinephrine administration via ET within the pediatric arrest model, but not for the adult.

scholarly journals Influence of Circulating Epinephrine and Norepinephrine on Insulin-Like Growth Factor Binding Protein-1 in Humans

1997 ◽  
Vol 82 (8) ◽  
pp. 2677-2680 ◽  
Author(s):  
Eva Fernqvist-Forbes ◽  
Agneta Hilding ◽  
Karin Ekberg ◽  
Kerstin Brismar
Keyword(s):  
Growth Factor ◽  
Binding Protein ◽  
Serum Insulin ◽  
Plasma Concentrations ◽  
Insulin Like Growth Factor ◽  
Blood Samples ◽  
C Peptide ◽  
Healthy Men ◽  
Factor Binding ◽  
Arterial Blood

The aim of the present study was to investigate the influence of circulating epinephrine (Epi) and norepinephrine (Norepi) on serum insulin-like growth factor binding protein-1 (IGFBP-1) concentrations. Healthy men received 0.3 nmol·kg·min Epi iv (n = 6), 0.5 nmol·kg·min Norepi iv (n = 7), or saline (n= 5) during 30 min. Arterial blood samples were obtained before, during, and 120 min after infusion. During the catecholamine infusion arterial Epi and Norepi plasma concentrations reached 6.35 ± 0.53 and 15.65 ± 2.71 nmol/L, respectively, which resulted in significant increases in glucose concentrations. When Epi was infused, IGFBP-1 increased from 45 ± 6 μg/L to 76 ± 10 μg/L (P &lt; 0.05) 60 min after the infusion. Epi was also followed by increases in insulin, C-peptide, and glucagon. Norepi resulted in a slight increase in circulating IGFBP-1 (43 ± 6 to 54 ± 8 nmol/L, NS). The findings suggest that Epi, at plasma concentrations similar to those reached during physical stress, stimulates the production of IGFBP-1 in humans.

Effect of tracer infusion site on measurement of bicarbonate-carbon dioxide metabolism in dogs

1986 ◽  
Vol 60 (4) ◽  
pp. 1248-1253 ◽  
Author(s):  
R. S. Downey ◽  
A. Mellone ◽  
D. E. Matthews
Keyword(s):  
Carbon Dioxide ◽  
Venous Blood ◽  
Co2 Flux ◽  
Infusion Site ◽  
Peripheral Vein ◽  
Arterial Infusion ◽  
Arterial Blood ◽  
Infusion Study ◽  
Significant Difference ◽  
The Mean

Ten dogs were given a primed infusion of H13CO3- for 220 min while under general anesthesia. Isotopic steady state was reached within 60 min in exhaled CO2, femoral arterial blood HCO3-, and femoral venous blood HCO3-. Halfway through each infusion study, the site of tracer infusion was changed either from the central aorta to a peripheral vein, or vice versa. The mean HCO3(-)-CO2 flux measured from blood HCO3- enrichments was 15.7 +/- 2.1 (SD) mmol X kg-1 X h-1. The mean fraction of tracer recovered in exhaled CO2 was 79 +/- 7% (SD) of the infused dose. No significant difference in either HCO3- flux or recovery of tracer was found between the venous and arterial infusions of tracer. These results indicate that when venous administration of HCO3- tracer is compared with central arterial infusion, the initial loss of tracer into expired CO2 is an unimportant consideration in experiments measuring HCO3- kinetics.

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