The Experts below are selected from a list of 14070 Experts worldwide ranked by ideXlab platform
James C. Eisenach - One of the best experts on this subject based on the ideXlab platform.
-
Neostigmine decreases bupivacaine use by patient controlled epidural analgesia during labor a randomized controlled study
Anesthesia & Analgesia, 2009Co-Authors: Vernon H Ross, Peter H Pan, Medge D Owen, Melvin H Seid, L C Harris, Brittany Clyne, Misa Voltaire, James C. EisenachAbstract:BACKGROUND Intrathecal Neostigmine not only produces analgesia but also severe nausea. In contrast, epidural Neostigmine enhances opioid and local anesthetic analgesia without causing nausea. Previous studies examined only single epidural Neostigmine bolus administration and did not assess the efficacy of continuous epidural infusion or several aspects of maternal and fetal safety. We therefore tested the hypothesis that epidural Neostigmine in combination with bupivacaine by continuous infusion during labor would reduce the amount of bupivacaine required. METHODS Twelve healthy women scheduled for elective cesarean delivery were assigned to receive epidural Neostigmine, 40 microg (first six subjects) or 80 microg (second six subjects) as a single bolus, with fetal heart rate (FHR) and uterine contractions monitored for 20 min. In a subsequent experiment, 40 healthy laboring women were randomized to receive bupivacaine 1.25 mg/mL alone or with Neostigmine 4 microg/mL by patient-controlled epidural analgesia. The primary outcome measure was hourly bupivacaine use. RESULTS Epidural Neostigmine bolus did not alter baseline FHR, induce contractions, or produce nausea. Epidural Neostigmine infusion reduced bupivacaine requirement by 19% in all patients and 25% in those with >4 h of treatment (P < 0.05 for both) but might have contributed to the incidence of mild sedation. Mode of delivery, incidence of maternal nausea, and FHR abnormality were similar between groups. CONCLUSIONS These data show that adding epidural Neostigmine 4 microg/mL reduces the hourly bupivacaine requirement by 19%-25% with patient-controlled epidural analgesia during labor. Administered as a bolus and by continuous infusion at the studied doses, epidural Neostigmine does not cause nausea and does not induce uterine contractions or FHR abnormalities, but mild sedation can occur.
-
Intrathecal Neostigmine and Sufentanil for Early Labor Analgesia
Anesthesiology, 1999Co-Authors: Kenneth E. Nelson, David D. Hood, Robert D'angelo, Michael L. Foss, Greg C. Meister, James C. EisenachAbstract:BACKGROUND Recent efforts to improve the combined spinal epidural (CSE) technique have focused on adding opioids to other classes of analgesics. In this study, the authors used intrathecal Neostigmine in combination with intrathecal sufentanil to investigate the usefulness of Neostigmine for reducing side effects and prolonging the duration of sufentanil. METHODS One hundred six healthy pregnant women in labor were enrolled in this study, which was divided into four phases. In all phases, patients received a CSE anesthetic while in the lateral position. In phase I, three groups of six women each received intrathecal Neostigmine, 5, 10, or 20 microg, in an open-label, dose-escalating safety assessment. In phase II, 24 women received intrathecal sufentanil alone to establish an ED50 (dose that produces > 60 min of labor analgesia in 50% of patients). In phase III, an ED50 was established for sufentanil combined with a fixed dose of Neostigmine (10 microg). In phase IV, 40 women received either twice the ED50 of sufentanil alone or twice the ED50 of sufentanil plus Neostigmine, 10 microg. RESULTS Neostigmine alone had no adverse effects on maternal vital signs, fetal heart rate, or Apgar scores. Neostigmine, 20 microg, produced analgesia in one patient and severe nausea and vomiting in another. The ED50 for intrathecal sufentanil alone was 4.1 +/- 0.31 microg, and the ED50 for intrathecal sufentanil combined with Neostigmine, 10 microg, was 3.0 +/- 0.28 microg. The duration of analgesia and side effects from double these ED50s (sufentanil, 9 microg, or sufentanil, 6 microg, plus Neostigmine, 10 microg) were similar between groups. CONCLUSIONS The 10-microg intrathecal Neostigmine dose alone produced no analgesia or side effects, but reduced the ED50 of intrathecal sufentanil by approximately 25%. Additionally, doses approximately double these ED50s each produced a similar duration of analgesia and side effects, indicating intrathecal Neostigmine shifts the dose-response curve for intrathecal sufentanil to the left.
-
Cerebrospinal Fluid Pharmacokinetics and Pharmacodynamics of Intrathecal Neostigmine Methylsulfate in Humans
Anesthesiology, 1998Co-Authors: Steven L. Shafer, David D. Hood, James C. Eisenach, Chuanyao TongAbstract:BACKGROUND This study defines the cerebrospinal fluid (CSF) pharmacokinetics of Neostigmine after intrathecal injection in humans and its effect on CSF acetylcholine, and it correlates physiologic effects with Neostigmine dose and CSF acetylcholine concentrations. METHODS The CSF was sampled via an indwelling spinal catheter in 12 volunteers receiving intrathecal Neostigmine (50-750 microg) and analyzed for Neostigmine and acetylcholine. Pharmacokinetic and pharmacodynamic analyses were performed with NONMEM. Effect-site models linked the time course of the Neostigmine concentration with the time course of analgesia. RESULTS Acetylcholine concentrations increased from 100 pmol/ml within 15 min of Neostigmine injection. The pharmacokinetics of intrathecal Neostigmine were best described by a triexponential function with an absorption phase. Individual predicted concentrations varied 100-fold. Post hoc Bayesian estimates described the observed Neostigmine concentrations with a median error of 22% and did not show systematic model misspecification. Individual estimates of effect site concentration producing a 50% maximal effect for foot visual analog scale analgesia correlated with the magnitude of individual CSF Neostigmine concentrations. CONCLUSIONS Intrathecal Neostigmine concentrations can be well described by a triexponential disposition function, but the intersubject variability is large. The correlation between intersubject variability in concentration and intersubject variability in 50% maximal effect for foot analgesia suggests that both are offset by a common scalar, possibly the distance from the site of injection to the sampling and effect sites. These data provide the basis for the hypothesis of "observation at a distance" to describe the pharmacodynamics of intrathecally administered drugs.
-
A Multi-center Study of Intrathecal Neostigmine for Analgesia following Vaginal Hysterectomy
Anesthesiology, 1998Co-Authors: Gabriela Rocha Lauretti, David D. Hood, James C. Eisenach, Ben L. PfeiferAbstract:BACKGROUND Intrathecal Neostigmine injection produces analgesia in volunteers and reduces hypotension from intrathecal bupivacaine in animals. Initial clinical trials with Neostigmine studied doses of more than 100 microg, but animal studies suggest that smaller doses may be effective. In addition, all controlled clinical trials of Neostigmine have come from one Brazilian university. This multicenter, placebo-controlled trial investigated the effects of 25-75 microg intrathecal Neostigmine on analgesia and blood pressure in women undergoing vaginal hysterectomy. METHODS After institutional review board approval was obtained at the three university centers, and after patients gave informed consent, 92 women scheduled for vaginal hysterectomy were randomized to receive an intrathecal injection of 2 ml bupivacaine, 0.75%, in dextrose plus either 1 ml saline or 25, 50, or 75 microg Neostigmine. Blood pressure, heart rate, pain and nausea (both assessed by visual analog scale), and intravenous morphine use were recorded during surgery and at specified intervals afterward. RESULTS Morphine use was reduced similarly by all doses of Neostigmine. Only the 75-microg dose of Neostigmine increased the nausea score in the recovery room. The incidence of treatment for nausea was greater in patients receiving Neostigmine (61%) than in those receiving saline placebo (29%) and was unaffected by Neostigmine dose. Neostigmine did not reduce the incidence of hypotension from bupivacaine. CONCLUSION These data in patients after vaginal hysterectomy suggest that analgesia from intrathecal Neostigmine may occur at doses less than 50 microg. In these doses, Neostigmine does not reduce spinal bupivacaine-induced hypotension but may increase the need for treatment of nausea.
-
phase i human safety assessment of intrathecal Neostigmine containing methyl and propylparabens
Anesthesia & Analgesia, 1997Co-Authors: James C. Eisenach, David D. Hood, Regina CurryAbstract:Intrathecal (IT) Neostigmine produces analgesia in humans with acute experimental, postoperative, and chronic pain.The sole manufacturer of the preservative-free Neostigmine solution used in the initial clinical studies no longer markets this preparation. Although solutions containing preservatives are generally avoided for IT injection, methyl- and propylparabens have not been demonstrated to be toxic. After preclinical toxicity screening in animals and Food and Drug Administration approval, 12 volunteers received IT Neostigmine 10, 30, or 100 micro g, containing these preservatives and glucose. This preparation produced dose-dependent analgesia, nausea, weakness, and sedation similar to the preservative-free preparation. IT Neostigmine increased acetylcholine but not norepinephrine concentrations in cerebrospinal fluid. Although nitric oxide synthesis has been implicated in analgesia from IT Neostigmine injection in animals, cerebrospinal fluid concentrations of nitrite as a measure of nitric oxide were not increased by IT Neostigmine in these volunteers. These data support the investigational application of IT Neostigmine containing methyl- and propylparabens in the concentrations studied. Implications: Because intrathecal injection of Neostigmine may be a useful analgesic, we performed a Phase I tolerability and safety study of the commercially available Neostigmine formulation in human volunteers and found no evidence of toxicity. These data are important to the clinical use of this new therapy. (Anesth Analg 1997;85:842-6)
Elliott Bennett-guerrero - One of the best experts on this subject based on the ideXlab platform.
-
A randomized-controlled trial of sugammadex versus Neostigmine: impact on early postoperative strength
Canadian Journal of Anesthesia Journal canadien d'anesthésie, 2020Co-Authors: Ramon E. Abola, Jamie Romeiser, Sabeen Rizwan, Brandon Lung, Ruchir Gupta, Elliott Bennett-guerreroAbstract:Contexte Les blocs neuromusculaires résiduels après une chirurgie sont associés à l’obstruction des voies aériennes, à l’hypoxie et à des complications respiratoires. Par rapport à la néostigmine, le sugammadex neutralise le bloc neuromusculaire à un ratio de train-de-quatre (TOF) > 0,9 plus rapidement. Nous ne savons toutefois pas si le profil de neutralisation supérieur du sugammadex améliore les mesures pertinentes d’un point de vue clinique de la force en période postopératoire initiale. Méthode Nous avons randomisé des patients subissant une chirurgie générale, gynécologique ou urologique à recevoir de la néostigmine (70 µg·kg^-1, maximum 5 mg) ou du sugammadex (2 ou 4 mg·kg^-1) pour neutraliser le bloc neuromusculaire. Le critère d’évaluation principal était la capacité des patients à respirer profondément telle que mesurée par spirométrie incitative à 30, 60 et 120 min après la neutralisation. Résultats Au total, 62 patients ont été randomisés dans les groupes néostigmine ( n = 31) ou sugammadex ( n = 31). Aucune différence dans la trajectoire de récupération de volume de spirométrie incitative n’a été observée entre les deux groupes ( P = 0,35). Les volumes médians de spirométrie préopératoire et à 30, 60 et 120 min postopératoires étaient de 2650 vs 2500 mL, 1775 vs 1750 mL, 1375 vs 2000 mL, et 1800 vs 1950 mL pour les groupes sugammadex et néostigmine, respectivement. La diminution postopératoire de la spirométrie incitative par rapport aux valeurs de base était similaire dans les deux groupes. La force de préhension, la capacité à s’asseoir sans assistance, le ratio de train-de-quatre à l’admission à la salle de réveil, le délai jusqu’à l’extubation, le délai jusqu’à l’obtention des critères de congé de la salle de réveil et les scores de QoR-15 (mesurant la qualité de récupération) ne différaient pas non plus entre les groupes. Conclusion Les mesures de la force postopératoire, telles que la spirométrie incitative, la force de préhension et la capacité de s’asseoir en période postopératoire initiale, ne différaient pas entre les patients ayant reçu de la néostigmine ou du sugammadex pour neutraliser le bloc neuromusculaire. Enregistrement de l’étude www.clinicaltrials.gov (NCT02909439); enregistrée le 21 septembre 2016. Background Residual neuromuscular blockade after surgery is associated with airway obstruction, hypoxia, and respiratory complications. Compared with Neostigmine, sugammadex reverses neuromuscular blockade to a train-of-four ratio > 0.9 more rapidly. It is unknown, however, whether the superior reversal profile of sugammadex improves clinically relevant measures of strength in the early postoperative period. Methods Patients undergoing general, gynecological, or urologic surgery were randomized to receive either Neostigmine (70 µg·kg^−1, maximum 5 mg) or sugammadex (2 or 4 mg·kg^−1) to reverse neuromuscular blockade. The primary outcome was the ability to breathe deeply measured by incentive spirometry at 30, 60, and 120 min after reversal. Results We randomized 62 patients to either a Neostigmine ( n = 31) or sugammadex ( n = 31) group. The incentive spirometry volume recovery trajectory was not different between the two groups ( P = 0.35). Median spirometry volumes at baseline, 30, 60, and 120 min postoperatively were 2650 vs 2500 mL, 1775 vs 1750 mL, 1375 vs 2000 mL, and 1800 vs 1950 mL for the sugammadex and Neostigmine groups, respectively. Postoperative incentive spirometry decrease from baseline was not different between the two groups. Hand grip strength, the ability to sit unaided, train-of-four ratio on postanesthesia care unit (PACU) admission, time to extubation, time to PACU discharge readiness, and Quality of Recovery-15 scores were also not different between the groups. Conclusions Measures of postoperative strength, such as incentive spirometry, hand group strength, and the ability to sit up in the early postoperative period were not different in patients who received Neostigmine or sugammadex for the reversal of neuromuscular blockade. Trial registration www.clinicaltrials.gov (NCT02909439); registered: 21 September, 2016.
-
A randomized-controlled trial of sugammadex versus Neostigmine: impact on early postoperative strength
Canadian Journal of Anesthesia Journal canadien d'anesthésie, 2020Co-Authors: Ramon E. Abola, Jamie Romeiser, Sabeen Rizwan, Brandon Lung, Ruchir Gupta, Elliott Bennett-guerreroAbstract:Contexte Les blocs neuromusculaires résiduels après une chirurgie sont associés à l’obstruction des voies aériennes, à l’hypoxie et à des complications respiratoires. Par rapport à la néostigmine, le sugammadex neutralise le bloc neuromusculaire à un ratio de train-de-quatre (TOF) > 0,9 plus rapidement. Nous ne savons toutefois pas si le profil de neutralisation supérieur du sugammadex améliore les mesures pertinentes d’un point de vue clinique de la force en période postopératoire initiale. Méthode Nous avons randomisé des patients subissant une chirurgie générale, gynécologique ou urologique à recevoir de la néostigmine (70 µg·kg^-1, maximum 5 mg) ou du sugammadex (2 ou 4 mg·kg^-1) pour neutraliser le bloc neuromusculaire. Le critère d’évaluation principal était la capacité des patients à respirer profondément telle que mesurée par spirométrie incitative à 30, 60 et 120 min après la neutralisation. Résultats Au total, 62 patients ont été randomisés dans les groupes néostigmine ( n = 31) ou sugammadex ( n = 31). Aucune différence dans la trajectoire de récupération de volume de spirométrie incitative n’a été observée entre les deux groupes ( P = 0,35). Les volumes médians de spirométrie préopératoire et à 30, 60 et 120 min postopératoires étaient de 2650 vs 2500 mL, 1775 vs 1750 mL, 1375 vs 2000 mL, et 1800 vs 1950 mL pour les groupes sugammadex et néostigmine, respectivement. La diminution postopératoire de la spirométrie incitative par rapport aux valeurs de base était similaire dans les deux groupes. La force de préhension, la capacité à s’asseoir sans assistance, le ratio de train-de-quatre à l’admission à la salle de réveil, le délai jusqu’à l’extubation, le délai jusqu’à l’obtention des critères de congé de la salle de réveil et les scores de QoR-15 (mesurant la qualité de récupération) ne différaient pas non plus entre les groupes. Conclusion Les mesures de la force postopératoire, telles que la spirométrie incitative, la force de préhension et la capacité de s’asseoir en période postopératoire initiale, ne différaient pas entre les patients ayant reçu de la néostigmine ou du sugammadex pour neutraliser le bloc neuromusculaire. Enregistrement de l’étude www.clinicaltrials.gov (NCT02909439); enregistrée le 21 septembre 2016. Background Residual neuromuscular blockade after surgery is associated with airway obstruction, hypoxia, and respiratory complications. Compared with Neostigmine, sugammadex reverses neuromuscular blockade to a train-of-four ratio > 0.9 more rapidly. It is unknown, however, whether the superior reversal profile of sugammadex improves clinically relevant measures of strength in the early postoperative period. Methods Patients undergoing general, gynecological, or urologic surgery were randomized to receive either Neostigmine (70 µg·kg^−1, maximum 5 mg) or sugammadex (2 or 4 mg·kg^−1) to reverse neuromuscular blockade. The primary outcome was the ability to breathe deeply measured by incentive spirometry at 30, 60, and 120 min after reversal. Results We randomized 62 patients to either a Neostigmine ( n = 31) or sugammadex ( n = 31) group. The incentive spirometry volume recovery trajectory was not different between the two groups ( P = 0.35). Median spirometry volumes at baseline, 30, 60, and 120 min postoperatively were 2650 vs 2500 mL, 1775 vs 1750 mL, 1375 vs 2000 mL, and 1800 vs 1950 mL for the sugammadex and Neostigmine groups, respectively. Postoperative incentive spirometry decrease from baseline was not different between the two groups. Hand grip strength, the ability to sit unaided, train-of-four ratio on postanesthesia care unit (PACU) admission, time to extubation, time to PACU discharge readiness, and Quality of Recovery-15 scores were also not different between the groups. Conclusions Measures of postoperative strength, such as incentive spirometry, hand group strength, and the ability to sit up in the early postoperative period were not different in patients who received Neostigmine or sugammadex for the reversal of neuromuscular blockade. Trial registration www.clinicaltrials.gov (NCT02909439); registered: 21 September, 2016.
David D. Hood - One of the best experts on this subject based on the ideXlab platform.
-
Intrathecal Neostigmine and Sufentanil for Early Labor Analgesia
Anesthesiology, 1999Co-Authors: Kenneth E. Nelson, David D. Hood, Robert D'angelo, Michael L. Foss, Greg C. Meister, James C. EisenachAbstract:BACKGROUND Recent efforts to improve the combined spinal epidural (CSE) technique have focused on adding opioids to other classes of analgesics. In this study, the authors used intrathecal Neostigmine in combination with intrathecal sufentanil to investigate the usefulness of Neostigmine for reducing side effects and prolonging the duration of sufentanil. METHODS One hundred six healthy pregnant women in labor were enrolled in this study, which was divided into four phases. In all phases, patients received a CSE anesthetic while in the lateral position. In phase I, three groups of six women each received intrathecal Neostigmine, 5, 10, or 20 microg, in an open-label, dose-escalating safety assessment. In phase II, 24 women received intrathecal sufentanil alone to establish an ED50 (dose that produces > 60 min of labor analgesia in 50% of patients). In phase III, an ED50 was established for sufentanil combined with a fixed dose of Neostigmine (10 microg). In phase IV, 40 women received either twice the ED50 of sufentanil alone or twice the ED50 of sufentanil plus Neostigmine, 10 microg. RESULTS Neostigmine alone had no adverse effects on maternal vital signs, fetal heart rate, or Apgar scores. Neostigmine, 20 microg, produced analgesia in one patient and severe nausea and vomiting in another. The ED50 for intrathecal sufentanil alone was 4.1 +/- 0.31 microg, and the ED50 for intrathecal sufentanil combined with Neostigmine, 10 microg, was 3.0 +/- 0.28 microg. The duration of analgesia and side effects from double these ED50s (sufentanil, 9 microg, or sufentanil, 6 microg, plus Neostigmine, 10 microg) were similar between groups. CONCLUSIONS The 10-microg intrathecal Neostigmine dose alone produced no analgesia or side effects, but reduced the ED50 of intrathecal sufentanil by approximately 25%. Additionally, doses approximately double these ED50s each produced a similar duration of analgesia and side effects, indicating intrathecal Neostigmine shifts the dose-response curve for intrathecal sufentanil to the left.
-
Cerebrospinal Fluid Pharmacokinetics and Pharmacodynamics of Intrathecal Neostigmine Methylsulfate in Humans
Anesthesiology, 1998Co-Authors: Steven L. Shafer, David D. Hood, James C. Eisenach, Chuanyao TongAbstract:BACKGROUND This study defines the cerebrospinal fluid (CSF) pharmacokinetics of Neostigmine after intrathecal injection in humans and its effect on CSF acetylcholine, and it correlates physiologic effects with Neostigmine dose and CSF acetylcholine concentrations. METHODS The CSF was sampled via an indwelling spinal catheter in 12 volunteers receiving intrathecal Neostigmine (50-750 microg) and analyzed for Neostigmine and acetylcholine. Pharmacokinetic and pharmacodynamic analyses were performed with NONMEM. Effect-site models linked the time course of the Neostigmine concentration with the time course of analgesia. RESULTS Acetylcholine concentrations increased from 100 pmol/ml within 15 min of Neostigmine injection. The pharmacokinetics of intrathecal Neostigmine were best described by a triexponential function with an absorption phase. Individual predicted concentrations varied 100-fold. Post hoc Bayesian estimates described the observed Neostigmine concentrations with a median error of 22% and did not show systematic model misspecification. Individual estimates of effect site concentration producing a 50% maximal effect for foot visual analog scale analgesia correlated with the magnitude of individual CSF Neostigmine concentrations. CONCLUSIONS Intrathecal Neostigmine concentrations can be well described by a triexponential disposition function, but the intersubject variability is large. The correlation between intersubject variability in concentration and intersubject variability in 50% maximal effect for foot analgesia suggests that both are offset by a common scalar, possibly the distance from the site of injection to the sampling and effect sites. These data provide the basis for the hypothesis of "observation at a distance" to describe the pharmacodynamics of intrathecally administered drugs.
-
A Multi-center Study of Intrathecal Neostigmine for Analgesia following Vaginal Hysterectomy
Anesthesiology, 1998Co-Authors: Gabriela Rocha Lauretti, David D. Hood, James C. Eisenach, Ben L. PfeiferAbstract:BACKGROUND Intrathecal Neostigmine injection produces analgesia in volunteers and reduces hypotension from intrathecal bupivacaine in animals. Initial clinical trials with Neostigmine studied doses of more than 100 microg, but animal studies suggest that smaller doses may be effective. In addition, all controlled clinical trials of Neostigmine have come from one Brazilian university. This multicenter, placebo-controlled trial investigated the effects of 25-75 microg intrathecal Neostigmine on analgesia and blood pressure in women undergoing vaginal hysterectomy. METHODS After institutional review board approval was obtained at the three university centers, and after patients gave informed consent, 92 women scheduled for vaginal hysterectomy were randomized to receive an intrathecal injection of 2 ml bupivacaine, 0.75%, in dextrose plus either 1 ml saline or 25, 50, or 75 microg Neostigmine. Blood pressure, heart rate, pain and nausea (both assessed by visual analog scale), and intravenous morphine use were recorded during surgery and at specified intervals afterward. RESULTS Morphine use was reduced similarly by all doses of Neostigmine. Only the 75-microg dose of Neostigmine increased the nausea score in the recovery room. The incidence of treatment for nausea was greater in patients receiving Neostigmine (61%) than in those receiving saline placebo (29%) and was unaffected by Neostigmine dose. Neostigmine did not reduce the incidence of hypotension from bupivacaine. CONCLUSION These data in patients after vaginal hysterectomy suggest that analgesia from intrathecal Neostigmine may occur at doses less than 50 microg. In these doses, Neostigmine does not reduce spinal bupivacaine-induced hypotension but may increase the need for treatment of nausea.
-
phase i human safety assessment of intrathecal Neostigmine containing methyl and propylparabens
Anesthesia & Analgesia, 1997Co-Authors: James C. Eisenach, David D. Hood, Regina CurryAbstract:Intrathecal (IT) Neostigmine produces analgesia in humans with acute experimental, postoperative, and chronic pain.The sole manufacturer of the preservative-free Neostigmine solution used in the initial clinical studies no longer markets this preparation. Although solutions containing preservatives are generally avoided for IT injection, methyl- and propylparabens have not been demonstrated to be toxic. After preclinical toxicity screening in animals and Food and Drug Administration approval, 12 volunteers received IT Neostigmine 10, 30, or 100 micro g, containing these preservatives and glucose. This preparation produced dose-dependent analgesia, nausea, weakness, and sedation similar to the preservative-free preparation. IT Neostigmine increased acetylcholine but not norepinephrine concentrations in cerebrospinal fluid. Although nitric oxide synthesis has been implicated in analgesia from IT Neostigmine injection in animals, cerebrospinal fluid concentrations of nitrite as a measure of nitric oxide were not increased by IT Neostigmine in these volunteers. These data support the investigational application of IT Neostigmine containing methyl- and propylparabens in the concentrations studied. Implications: Because intrathecal injection of Neostigmine may be a useful analgesic, we performed a Phase I tolerability and safety study of the commercially available Neostigmine formulation in human volunteers and found no evidence of toxicity. These data are important to the clinical use of this new therapy. (Anesth Analg 1997;85:842-6)
-
enhancement of analgesia from systemic opioid in humans by spinal cholinesterase inhibition
Journal of Pharmacology and Experimental Therapeutics, 1997Co-Authors: David D. Hood, Robin Tuttle, Kathryn A Mallak, Robert L James, James C. EisenachAbstract:Intravenous opioids cause analgesia and increase release of ACh in spinal cord dorsal horn in animals, and these effects are enhanced by intrathecal Neostigmine injection. The purpose of the current study was to test whether intrathecal Neostigmine enhanced analgesia and increased cerebrospinal fluid concentrations of ACh over those induced by i.v. alfentanil in volunteers, and also to test whether Neostigmine enhanced alfentanil-induced side effects. After human studies committee approval, 40 healthy volunteers received an intrathecal injection of saline or Neostigmine (50, 100 or 200 μg) followed in 60 min by a computer-controlled, stepped i.v. infusion of alfentanil to escalating targeted plasma concentrations. Pain report to hand and foot immersion in ice water, sedation, nausea, weakness, vital signs, end-tidal CO2 and oxyhemoglobin saturation were measured 60 min after spinal injection and at the end of each 20-min alfentanil infusion. Cerebrospinal fluid was sampled once after drug administration. Intrathecal Neostigmine alone caused analgesia in the foot but not in the hand, and was accompanied by leg weakness, whereas IV alfentanil alone caused equivalent analgesia in both the hand and the foot and was accompanied by nausea, sedation, increased end-tidal CO2and decreased oxyhemoglobin saturation. Neostigmine enhanced analgesia but not respiratory effects induced by i.v. alfentanil; it also enhanced nausea and sedation. Intravenous alfentanil increased cerebrospinal fluid ACh concentration, and Neostigmine enhanced this change. These data in humans are consistent with a spinal cholinergic mechanism of i.v. opioid analgesia. Because Neostigmine enhances both analgesia and side effects induced by i.v. alfentanil, the clinical utility of their use in combination will depend on the relative strength of these interactions.
M E Prins - One of the best experts on this subject based on the ideXlab platform.
-
reversal of rocuronium induced neuromuscular block with sugammadex is faster than reversal of cisatracurium induced block with Neostigmine
BJA: British Journal of Anaesthesia, 2008Co-Authors: Ea Flockton, J.m. Hunter, C Meistelman, P Mastronardi, C Gomar, R K Mirakhur, L Aguilera, Francesco Giunta, M E PrinsAbstract:Abstract Background Reversal of the residual effect of rocuronium or cisatracurium by Neostigmine may be slow and associated with side-effects. This randomized, safety-assessor-blinded study compared the efficacy of sugammadex, a selective relaxant binding agent for reversal of rocuronium-induced neuromuscular block, with that of Neostigmine for reversal of cisatracurium-induced neuromuscular block. The safety of sugammadex and Neostigmine was also evaluated. Methods Adult surgical patients (ASA class I–III) were randomized to sugammadex 2.0 mg kg −1 for reversal of block induced by rocuronium 0.6 mg kg −1 , or Neostigmine 50 μg kg −1 for reversal of block induced by cisatracurium 0.15 mg kg −1 . Anaesthesia was induced and maintained using i.v. propofol and remifentanil, fentanyl, or sufentanil. Neuromuscular function was monitored using acceleromyography (TOF-Watch ® SX). Sugammadex or Neostigmine was administered at reappearance of T 2 . The primary efficacy variable was time for recovery of the train-of-four (TOF) ratio to 0.9. Results Eighty-four patients were randomized, 73 of whom received sugammadex ( n =34) or Neostigmine ( n =39). Time from start of administration of reversal agent to recovery of the TOF ratio to 0.9 was 4.7 times faster with sugammadex than with Neostigmine (geometric mean=1.9 vs 9.0 min, P N -acetyl glucosaminidase in both groups. Conclusions Sugammadex 2.0 mg kg −1 administered at reappearance of T 2 was significantly faster in reversing rocuronium-induced blockade than Neostigmine was in reversing cisatracurium-induced block.
-
reversal of rocuronium induced neuromuscular block with sugammadex is faster than reversal of cisatracurium induced block with Neostigmine
BJA: British Journal of Anaesthesia, 2008Co-Authors: Ea Flockton, J.m. Hunter, C Meistelman, P Mastronardi, C Gomar, R K Mirakhur, L Aguilera, Francesco Giunta, M E PrinsAbstract:Abstract Background Reversal of the residual effect of rocuronium or cisatracurium by Neostigmine may be slow and associated with side-effects. This randomized, safety-assessor-blinded study compared the efficacy of sugammadex, a selective relaxant binding agent for reversal of rocuronium-induced neuromuscular block, with that of Neostigmine for reversal of cisatracurium-induced neuromuscular block. The safety of sugammadex and Neostigmine was also evaluated. Methods Adult surgical patients (ASA class I–III) were randomized to sugammadex 2.0 mg kg−1 for reversal of block induced by rocuronium 0.6 mg kg−1, or Neostigmine 50 μg kg−1 for reversal of block induced by cisatracurium 0.15 mg kg−1. Anaesthesia was induced and maintained using i.v. propofol and remifentanil, fentanyl, or sufentanil. Neuromuscular function was monitored using acceleromyography (TOF-Watch® SX). Sugammadex or Neostigmine was administered at reappearance of T2. The primary efficacy variable was time for recovery of the train-of-four (TOF) ratio to 0.9. Results Eighty-four patients were randomized, 73 of whom received sugammadex (n=34) or Neostigmine (n=39). Time from start of administration of reversal agent to recovery of the TOF ratio to 0.9 was 4.7 times faster with sugammadex than with Neostigmine (geometric mean=1.9 vs 9.0 min, P Conclusions Sugammadex 2.0 mg kg−1 administered at reappearance of T2 was significantly faster in reversing rocuronium-induced blockade than Neostigmine was in reversing cisatracurium-induced block.
Ramon E. Abola - One of the best experts on this subject based on the ideXlab platform.
-
A randomized-controlled trial of sugammadex versus Neostigmine: impact on early postoperative strength
Canadian Journal of Anesthesia Journal canadien d'anesthésie, 2020Co-Authors: Ramon E. Abola, Jamie Romeiser, Sabeen Rizwan, Brandon Lung, Ruchir Gupta, Elliott Bennett-guerreroAbstract:Contexte Les blocs neuromusculaires résiduels après une chirurgie sont associés à l’obstruction des voies aériennes, à l’hypoxie et à des complications respiratoires. Par rapport à la néostigmine, le sugammadex neutralise le bloc neuromusculaire à un ratio de train-de-quatre (TOF) > 0,9 plus rapidement. Nous ne savons toutefois pas si le profil de neutralisation supérieur du sugammadex améliore les mesures pertinentes d’un point de vue clinique de la force en période postopératoire initiale. Méthode Nous avons randomisé des patients subissant une chirurgie générale, gynécologique ou urologique à recevoir de la néostigmine (70 µg·kg^-1, maximum 5 mg) ou du sugammadex (2 ou 4 mg·kg^-1) pour neutraliser le bloc neuromusculaire. Le critère d’évaluation principal était la capacité des patients à respirer profondément telle que mesurée par spirométrie incitative à 30, 60 et 120 min après la neutralisation. Résultats Au total, 62 patients ont été randomisés dans les groupes néostigmine ( n = 31) ou sugammadex ( n = 31). Aucune différence dans la trajectoire de récupération de volume de spirométrie incitative n’a été observée entre les deux groupes ( P = 0,35). Les volumes médians de spirométrie préopératoire et à 30, 60 et 120 min postopératoires étaient de 2650 vs 2500 mL, 1775 vs 1750 mL, 1375 vs 2000 mL, et 1800 vs 1950 mL pour les groupes sugammadex et néostigmine, respectivement. La diminution postopératoire de la spirométrie incitative par rapport aux valeurs de base était similaire dans les deux groupes. La force de préhension, la capacité à s’asseoir sans assistance, le ratio de train-de-quatre à l’admission à la salle de réveil, le délai jusqu’à l’extubation, le délai jusqu’à l’obtention des critères de congé de la salle de réveil et les scores de QoR-15 (mesurant la qualité de récupération) ne différaient pas non plus entre les groupes. Conclusion Les mesures de la force postopératoire, telles que la spirométrie incitative, la force de préhension et la capacité de s’asseoir en période postopératoire initiale, ne différaient pas entre les patients ayant reçu de la néostigmine ou du sugammadex pour neutraliser le bloc neuromusculaire. Enregistrement de l’étude www.clinicaltrials.gov (NCT02909439); enregistrée le 21 septembre 2016. Background Residual neuromuscular blockade after surgery is associated with airway obstruction, hypoxia, and respiratory complications. Compared with Neostigmine, sugammadex reverses neuromuscular blockade to a train-of-four ratio > 0.9 more rapidly. It is unknown, however, whether the superior reversal profile of sugammadex improves clinically relevant measures of strength in the early postoperative period. Methods Patients undergoing general, gynecological, or urologic surgery were randomized to receive either Neostigmine (70 µg·kg^−1, maximum 5 mg) or sugammadex (2 or 4 mg·kg^−1) to reverse neuromuscular blockade. The primary outcome was the ability to breathe deeply measured by incentive spirometry at 30, 60, and 120 min after reversal. Results We randomized 62 patients to either a Neostigmine ( n = 31) or sugammadex ( n = 31) group. The incentive spirometry volume recovery trajectory was not different between the two groups ( P = 0.35). Median spirometry volumes at baseline, 30, 60, and 120 min postoperatively were 2650 vs 2500 mL, 1775 vs 1750 mL, 1375 vs 2000 mL, and 1800 vs 1950 mL for the sugammadex and Neostigmine groups, respectively. Postoperative incentive spirometry decrease from baseline was not different between the two groups. Hand grip strength, the ability to sit unaided, train-of-four ratio on postanesthesia care unit (PACU) admission, time to extubation, time to PACU discharge readiness, and Quality of Recovery-15 scores were also not different between the groups. Conclusions Measures of postoperative strength, such as incentive spirometry, hand group strength, and the ability to sit up in the early postoperative period were not different in patients who received Neostigmine or sugammadex for the reversal of neuromuscular blockade. Trial registration www.clinicaltrials.gov (NCT02909439); registered: 21 September, 2016.
-
A randomized-controlled trial of sugammadex versus Neostigmine: impact on early postoperative strength
Canadian Journal of Anesthesia Journal canadien d'anesthésie, 2020Co-Authors: Ramon E. Abola, Jamie Romeiser, Sabeen Rizwan, Brandon Lung, Ruchir Gupta, Elliott Bennett-guerreroAbstract:Contexte Les blocs neuromusculaires résiduels après une chirurgie sont associés à l’obstruction des voies aériennes, à l’hypoxie et à des complications respiratoires. Par rapport à la néostigmine, le sugammadex neutralise le bloc neuromusculaire à un ratio de train-de-quatre (TOF) > 0,9 plus rapidement. Nous ne savons toutefois pas si le profil de neutralisation supérieur du sugammadex améliore les mesures pertinentes d’un point de vue clinique de la force en période postopératoire initiale. Méthode Nous avons randomisé des patients subissant une chirurgie générale, gynécologique ou urologique à recevoir de la néostigmine (70 µg·kg^-1, maximum 5 mg) ou du sugammadex (2 ou 4 mg·kg^-1) pour neutraliser le bloc neuromusculaire. Le critère d’évaluation principal était la capacité des patients à respirer profondément telle que mesurée par spirométrie incitative à 30, 60 et 120 min après la neutralisation. Résultats Au total, 62 patients ont été randomisés dans les groupes néostigmine ( n = 31) ou sugammadex ( n = 31). Aucune différence dans la trajectoire de récupération de volume de spirométrie incitative n’a été observée entre les deux groupes ( P = 0,35). Les volumes médians de spirométrie préopératoire et à 30, 60 et 120 min postopératoires étaient de 2650 vs 2500 mL, 1775 vs 1750 mL, 1375 vs 2000 mL, et 1800 vs 1950 mL pour les groupes sugammadex et néostigmine, respectivement. La diminution postopératoire de la spirométrie incitative par rapport aux valeurs de base était similaire dans les deux groupes. La force de préhension, la capacité à s’asseoir sans assistance, le ratio de train-de-quatre à l’admission à la salle de réveil, le délai jusqu’à l’extubation, le délai jusqu’à l’obtention des critères de congé de la salle de réveil et les scores de QoR-15 (mesurant la qualité de récupération) ne différaient pas non plus entre les groupes. Conclusion Les mesures de la force postopératoire, telles que la spirométrie incitative, la force de préhension et la capacité de s’asseoir en période postopératoire initiale, ne différaient pas entre les patients ayant reçu de la néostigmine ou du sugammadex pour neutraliser le bloc neuromusculaire. Enregistrement de l’étude www.clinicaltrials.gov (NCT02909439); enregistrée le 21 septembre 2016. Background Residual neuromuscular blockade after surgery is associated with airway obstruction, hypoxia, and respiratory complications. Compared with Neostigmine, sugammadex reverses neuromuscular blockade to a train-of-four ratio > 0.9 more rapidly. It is unknown, however, whether the superior reversal profile of sugammadex improves clinically relevant measures of strength in the early postoperative period. Methods Patients undergoing general, gynecological, or urologic surgery were randomized to receive either Neostigmine (70 µg·kg^−1, maximum 5 mg) or sugammadex (2 or 4 mg·kg^−1) to reverse neuromuscular blockade. The primary outcome was the ability to breathe deeply measured by incentive spirometry at 30, 60, and 120 min after reversal. Results We randomized 62 patients to either a Neostigmine ( n = 31) or sugammadex ( n = 31) group. The incentive spirometry volume recovery trajectory was not different between the two groups ( P = 0.35). Median spirometry volumes at baseline, 30, 60, and 120 min postoperatively were 2650 vs 2500 mL, 1775 vs 1750 mL, 1375 vs 2000 mL, and 1800 vs 1950 mL for the sugammadex and Neostigmine groups, respectively. Postoperative incentive spirometry decrease from baseline was not different between the two groups. Hand grip strength, the ability to sit unaided, train-of-four ratio on postanesthesia care unit (PACU) admission, time to extubation, time to PACU discharge readiness, and Quality of Recovery-15 scores were also not different between the groups. Conclusions Measures of postoperative strength, such as incentive spirometry, hand group strength, and the ability to sit up in the early postoperative period were not different in patients who received Neostigmine or sugammadex for the reversal of neuromuscular blockade. Trial registration www.clinicaltrials.gov (NCT02909439); registered: 21 September, 2016.