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

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.

1999 ◽  
Vol 91 (6) ◽  
pp. 1780-1780 ◽  
Author(s):  
Jette A. Kuipers ◽  
Fred Boer ◽  
Wim Olieman ◽  
Anton G. L. Burm ◽  
James G. Bovill

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.


2000 ◽  
Vol 93 (4) ◽  
pp. 986-991 ◽  
Author(s):  
Yan-Ling He ◽  
Hiroshi Ueyama ◽  
Chikara Tashiro ◽  
Takashi Mashimo ◽  
Ikuto Yoshiya

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.


1989 ◽  
Vol 28 (03) ◽  
pp. 100-104 ◽  
Author(s):  
S. F. Akber

The first-pass pulmonary extraction values of N-lsopropyl-123l-p-lodoamphetamine (123I-IMP) in pretreated dogs decreases from 90 to 62% as the amount of propranolol increases from 0 to 20 mg. The first-pass pulmonary extraction values of 123I-IMP in dogs with a simultaneous bolus injection of propranolol decreases from 90 to 62% as the amount of propranolol increases from 0 to 10 mg. The pulmonary extraction of 123I-IMP with a simultaneous bolus injection of ketamine and 123I-IMP decreases from 90 to 64% as the ketamine dose increases from 0 to 100 mg. These results suggest that the pulmonary uptake of 123I-IMP may be at least partially mediated by receptors. They also indicate that endothelial metabolic cell function may be a useful index of early lung pathology. Furthermore, studies of the degree of lung uptake may be a sensitive index of pathologic states in which alterations of amine binding sites have occurred.


2012 ◽  
Vol 51 (No. 2) ◽  
pp. 55-59 ◽  
Author(s):  
K. Besoluk ◽  
E. Eken ◽  
S. Bahar

The aim of this study was to reveal the branches of the descending palatine artery, and its relation to the vomeronasal organ inAngoragoats. For this purpose, ten heads of adultAngoragoats obtained from a slaughterhouse were used. The ramifications of the latex enjected descending palatine artery and their vomeronasal organ-related findings were revealed by fine dissection and transverse sections. Arterial blood reached the caudally vomeronasal organ primarily via the sphenopalatine artery, and also cranially via a fine branch of the major palatine artery by crossing the palatine fissure. The average diameters of both the descending palatine artery and its branches were thicker on the left side than on the right, and its ramifications were not variable in this species.


1985 ◽  
Vol 58 (4) ◽  
pp. 1092-1098 ◽  
Author(s):  
M. D. Walkenstein ◽  
B. T. Peterson ◽  
J. E. Gerber ◽  
R. W. Hyde

Histological studies provide evidence that the bronchial veins are a site of leakage in histamine-induced pulmonary edema, but the physiological importance of this finding is not known. To determine if a lung perfused by only the bronchial arteries could develop pulmonary edema, we infused histamine for 2 h in anesthetized sheep with no pulmonary arterial blood flow to the right lung. In control sheep the postmortem extravascular lung water volume (EVLW) in both the right (occluded) and left (perfused) lung was 3.7 +/- 0.4 ml X g dry lung wt-1. Following histamine infusion, EVLW increased to 4.4 +/- 0.7 ml X g dry lung wt-1 in the right (occluded) lung (P less than 0.01) and to 5.3 +/- 1.0 ml X g dry wt-1 in the left (perfused) lung (P less than 0.01). Biopsies from the right (occluded) lungs scored for the presence of edema showed a significantly higher score in the lungs that received histamine (P less than 0.02). Some leakage from the pulmonary circulation of the right lung, perfused via anastomoses from the bronchial circulation, cannot be excluded but should be modest considering the low pressures in the pulmonary circulation following occlusion of the right pulmonary artery. These data show that perfusion via the pulmonary arteries is not a requirement for the production of histamine-induced pulmonary edema.


2013 ◽  
Vol 114 (10) ◽  
pp. 1406-1412 ◽  
Author(s):  
Angela S. M. Salinet ◽  
Thompson G. Robinson ◽  
Ronney B. Panerai

The association between neural activity and cerebral blood flow (CBF) has been used to assess neurovascular coupling (NVC) in health and diseases states, but little attention has been given to the contribution of simultaneous changes in peripheral covariates. We used an innovative approach to assess the contributions of arterial blood pressure (BP), PaCO2, and the stimulus itself to changes in CBF velocities (CBFv) during active (MA), passive (MP), and motor imagery (MI) paradigms. Continuous recordings of CBFv, beat-to-beat BP, heart rate, and breath-by-breath end-tidal CO2 (EtCO2) were performed in 17 right-handed subjects before, during, and after motor-cognitive paradigms performed with the right arm. A multivariate autoregressive-moving average model was used to calculate the separate contributions of BP, EtCO2, and the neural activation stimulus (represented by a metronome on-off signal) to the CBFv response during paradigms. Differences were found in the bilateral CBFv responses to MI compared with MA and MP, due to the contributions of stimulation ( P < 0.05). BP was the dominant contributor to the initial peaked CBFv response in all paradigms with no significant differences between paradigms, while the contribution of the stimulus explained the plateau phase and extended duration of the CBFv responses. Separating the neural activation contribution from the influences of other covariates, it was possible to detect differences between three paradigms often used to assess disease-related NVC. Apparently similar CBFv responses to different motor-cognitive paradigms can be misleading due to the contributions from peripheral covariates and could lead to inaccurate assessment of NVC, particularly during MI.


1999 ◽  
Vol 90 (4) ◽  
pp. 951-955 ◽  
Author(s):  
Gilles Dhonneur ◽  
Krassen Kirov ◽  
Velislav Slavov ◽  
Philippe Duvaldestin

Background Paralysis of the vocal cords is one objective of using relaxants to facilitate tracheal intubation. This study compares the neuromuscular blocking effect of succinylcholine and rocuronium on the larynx, the diaphragm, and the adductor pollicis muscle. Methods Electromyographic response was used to compare the neuromuscular blocking effect of succinylcholine and rocuronium on the laryngeal adductor muscles, the diaphragm, and the adductor pollicis muscle. Sixteen patients undergoing elective surgery were anesthetized with propofol and fentanyl, and their tracheas were intubated without neuromuscular blocking agents. The recurrent laryngeal and phrenic nerves were stimulated at the neck. The electromyographic response was recorded from electrodes placed on the endotracheal tube and intercostally before and after administration of 1 mg/kg succinylcholine or 0.6 mg/kg rocuronium. Results The maximum effect was greater at the adductor pollicis (100 and 99%) than at the larynx (96 and 97%) and the diaphragm (94 and 96%) after administration of succinylcholine and rocuronium, respectively (P &lt; or = 0.05). Onset time was not different between the larynx (58+/-10 s), the diaphragm (57+/-8 s), and the adductor pollicis (54+/-13 s), after succinylcholine (all mean +/- SD). After rocuronium, onset time was 124+/-39 s at the larynx, 130+/-44 s at the diaphragm, and 115+/-21 s at the adductor pollicis. After succinylcholine administration, time to 90% recovery was 8.3+/-3.2, 7.2+/-3.5, and 9.1+/-3.0 min at the larynx, the diaphragm, and the adductor pollicis, respectively. Time to 90% recovery after rocuronium administration was 34.9+/-7.6, 30.4+/-4.2, and 49.1+/-11.4 min at the larynx, the diaphragm, and the adductor pollicis, respectively. Conclusion Neuromuscular blocking effect of muscle relaxants on the larynx can be measured noninvasively by electromyography. Although the larynx appears to be resistant to muscle relaxants, we could not demonstrate that its onset time differed from that of peripheral muscles.


2021 ◽  
Vol 2021 ◽  
pp. 1-8
Author(s):  
Shahryar Sane ◽  
Shahram Shokouhi ◽  
Parang Golabi ◽  
Mona Rezaeian ◽  
Behzad Kazemi Haki

Background. Brachial plexus block is frequently recommended for upper limb surgeries. Many drugs have been used as adjuvants to prolong the duration of the block. This study aimed to assess the effect of dexmedetomidine with bupivacaine combination and only bupivacaine on sensory and motor block duration time, pain score, and hemodynamic variations in the supraclavicular block in upper extremity orthopedic surgery. Methods. This prospective, double-blind clinical trial study was conducted on 60 patients, 20 to 60 years old. Patients were candidates for upper extremity orthopedic surgeries. The sensory and motor block were evaluated by using the pinprick method and the modified Bromage scale. The postoperative pain was assessed by utilizing a visual analog scale. Results. The mean onset time of sensory and motor block in patients receiving only bupivacaine was, respectively, 31.03 ± 9.65 min and 24.66 ± 9.2 min, and in the dexmedetomidine receiving group, it was about 21.36 ± 8.34 min and 15.93 ± 6.36 minutes. The changes in heart rate and mean arterial blood pressure were similar in both groups. The duration of sensory and motor block and the time of the first analgesia request in the intervention group were longer. Postoperative pain was lower in the intervention group for 24 hours ( P  = 0.001). Conclusion. Dexmedetomidine plus bupivacaine reduced the onset time of sense and motor blocks and increased numbness and immobility duration. Also, dexmedetomidine reduced postoperative pain significantly with the use of bupivacaine for supraclavicular blocks. Trial Registration. IRCT, IRCT20160430027677N15. Registered 05/28/2019, https://www.irct.ir/trial/39463.


2018 ◽  
Vol 61 (1) ◽  
pp. 37-39 ◽  
Author(s):  
Dimitrios Patoulias ◽  
Vasileios Rafailidis ◽  
Thomas Feidantsis ◽  
Maria Kalogirou ◽  
Dimitrios Rafailidis ◽  
...  

The acute idiopathic scrotal edema (AISE) is a self-limited disease of unknown etiology, characterized by edema and erythema of the scrotum and the dartos, without expansion to the underlying layers of scrotum’s wall or to the endoscrotal structures. Boys younger than 10 years old are usually involved in 60–90% of all cases. Diagnosis is made after exclusion of other causes of acute scrotum. We present a case of a 7-year old boy, who was admitted to the Emergency Department due to development of scrotal edema and erythema over the last 48 hours, which extended to the base of the penis. The patient mentioned that he first noticed the erythema on the anterior surface of the right hemiscrotum, which gradually extended. Physical examination did not reveal presence of pathology involving the endoscrotal structures, indicative of need for urgent surgical intervention. Transillumination was negative for blue dot sign. Ultrasonographic examination of the scrotum documented the homogeneity of the testicular parenchyma, while color Doppler revealed the presence of fountain’s sign (equal arterial blood supply to both testicles). Conservative strategy was followed and the patient gradually improved within the next three days. In conclusion, meticulous physical examination along with ultrasonographic examination of the suffering scrotum, especially with the highlighting of fountain’s sign with color Doppler, document the diagnosis of AISE. Thus, need for urgent surgical investigation of the suffering scrotum due to diagnostic doubt is limited.


1992 ◽  
Vol 262 (3) ◽  
pp. R524-R529 ◽  
Author(s):  
N. D. Binder ◽  
D. F. Anderson

We examined the relationship between acute reductions in renal perfusion pressure, as approximated by femoral arterial blood pressure, and plasma renin activity in the uninephrectomized fetal lamb. Renal perfusion pressure was reduced and maintained at a constant value by controlled partial occlusion of the aorta above the renal artery. After 15 min of reduced blood pressure, blood samples were taken for determination of plasma renin activity. This protocol was performed 22 times in 11 fetal lambs. Additionally, three of the fetuses were delivered by cesarean section and studied as newborns for the first week of life. In the fetus, there was a linear relationship between log plasma renin activity and femoral arterial blood pressure (P less than 0.01). After birth, the relationship still existed, although it was shifted to the right (P less than 0.0001). We conclude that there is a significant relationship between plasma renin activity and renal perfusion pressure in the fetal lamb, and as early as 1 day after birth, this relationship shifts to the right in the newborn lamb.


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