This document discusses lidocaine use as a local anesthetic in cosmetic surgery procedures. It provides dosages used in tumescent techniques, which allow higher lidocaine doses of 35-55 mg/kg. Studies found lidocaine concentrations below toxic levels after infiltration of 2000-5600 mg total doses. The slow absorption from subcutaneous fat tissue and epinephrine's effects are believed to allow safe higher doses. Approximately 10-31% of infiltrated lidocaine is removed during liposuction, while the metabolite MEGX reaches plasma levels comparable to lidocaine. Higher neck vs thigh infiltrations were associated with faster time to peak lidocaine concentrations.
The essential use of parecoxib in post operative pain management speaker (1)Setyadi Soeroyo
Presentasi ini tentang obat nyeri yang aman untuk lambung, selain itu obat ini tidak mengganggu pembekuan darah. Parecoxib adalah jenis analgetik cox2. Penggunaan untuk pasien dengan kelainan jantung dan pada penderita kelainan ginjal harus hati-hati.
Effectiveness of intra-articular dexmedetomidine as postoperative analgesia i...iosrphr_editor
Background And Objectives: To study the effect of inj.Ropivacaine (0.25%) 2mg/kg with and without Inj.Dexmedetomidine (1-2μg/kg) intraarticularly for postoperative analgesia in arthroscopic knee surgery.1:To Evaluate Onset, Duration and analgesic efficacy of Intraarticular Dexmedetomidine2: To monitor the safety of Dexmedetomidine and Ropivacaine.
Methods: A prospective randomized double blind study, was conducted in 50 patients undergoing elective arthroscopy of knee joint under spinal anaesthesia. At the completion of the surgery, all patients were divied into two groups;GroupP(n=25):received Inj. Ropivacaine 0.25% and GroupD(n=25):received Inj.Ropivacaine(0.25%)+Inj. Dexmedetomidine(1μg/kg) total volume 20 ml was deposited intra-articularly.Patients were monitored in the postoperative ward for the hemodynamic parameters and their Sedation score was assessed.. The efficacy of the drug was determined by improvement in VAS score, duration of analgesia and total number of rescue analgesics during 24 hr in post operative period.
Results: There was no statistically significant differences observed in heart rate except changes at 6 and 8 hr. At 6 and 8 hr in group P pulse (82.48 ± 7.49, 81.44 ± 8.78) as compared to group D (75.38 ± 6.52, 74.96 ± 5.70),because of duration of action of ropivacaine with or without dexmedetomidine.There was no statistically significant difference in blood pressure was found, except at 12 hour and 24 hour (p=0.018), because of longer duration of action of intrarticular dexmedetomidine with ropivacaine in group D.At 6 hrs patients in Group P had a mean VAS score of 3.2 as compared to VAS score values of 1.8 in Group D which is statistically significant..At 2 , 4, 6 and 8 hour VAS score in P group was 1.64, 2.44, 3.24, 2.84 respectively. As compared to group P, in group D VAS score at 2, 4, 6 and 8 hour was 0.92, 1.04, 1.79 and 2.08 respectively. So VAS score lower in group D as compared to group P at 2, 4, 6 and 8 hrs.
A Prospective comparative study of Local anaesthesia & Spinal anaesthesia for...iosrjce
IOSR Journal of Dental and Medical Sciences is one of the speciality Journal in Dental Science and Medical Science published by International Organization of Scientific Research (IOSR). The Journal publishes papers of the highest scientific merit and widest possible scope work in all areas related to medical and dental science. The Journal welcome review articles, leading medical and clinical research articles, technical notes, case reports and others.
PowerPoint. Nonradioactive iodine competes with radioactive iodine. This has implications for the use of recombinant human TSH (rhTSH) when preparing differentiated thyroid cancer patients for radioiodine scanning with continued levothyroxine, because the latter contains iodine.
Evaluation of Effect of Low Dose Fentanyl, Dexmedetomidine and Clonidine in S...iosrjce
In the present study effect of intrathecal hyperbaric Bupivacaine 0.5% with low doses of Clonidine
or Fentanyl or Dexmedetomidine were compared in elective lower abdominal surgeries. This was a prospective
randomized control trial. 90 patients belonging to ASA 1 &II, aged between 20-50 years were allocated into
three groups. Group-C: Clonidine 30µg, Group-D: Dexmedetomidine 5 µg, Group-F: Fentanyl 25 µg. The
onset of sensory blockade was comparable in all the three groups. The onset of motor blockade was earlier by
about 1.3 mins in Dexmedetomidine group when compared to Clonidine and Fentanyl group. Duration of
sensory blockade was prolonged in Dexmedetomidine group (346mins) when compared to Clonidine (300mins)
and Fentanyl (302mins) group. Time duration of motor blockade was prolonged in Dexmedetomidine group
(269mins) when compared to Clonidine (223mins) and Fentanyl (220mins) group. The haemodynamic
parameters were clinically and statistically insignificant The time of first request for analgesics by the patients
was more in Dexmedetomidine group (250mins) when compared to Clonidine (194mins) and Fentanyl
(189mins) group. The use of intrathecal Dexmedetomidine as an adjuvant to Bupivacaine is an attractive
alternative to Fentanyl or Clonidine for long duration surgical procedures due to its profound intrathecal
anesthetic and analgesic properties combined with minimal side effects.
The essential use of parecoxib in post operative pain management speaker (1)Setyadi Soeroyo
Presentasi ini tentang obat nyeri yang aman untuk lambung, selain itu obat ini tidak mengganggu pembekuan darah. Parecoxib adalah jenis analgetik cox2. Penggunaan untuk pasien dengan kelainan jantung dan pada penderita kelainan ginjal harus hati-hati.
Effectiveness of intra-articular dexmedetomidine as postoperative analgesia i...iosrphr_editor
Background And Objectives: To study the effect of inj.Ropivacaine (0.25%) 2mg/kg with and without Inj.Dexmedetomidine (1-2μg/kg) intraarticularly for postoperative analgesia in arthroscopic knee surgery.1:To Evaluate Onset, Duration and analgesic efficacy of Intraarticular Dexmedetomidine2: To monitor the safety of Dexmedetomidine and Ropivacaine.
Methods: A prospective randomized double blind study, was conducted in 50 patients undergoing elective arthroscopy of knee joint under spinal anaesthesia. At the completion of the surgery, all patients were divied into two groups;GroupP(n=25):received Inj. Ropivacaine 0.25% and GroupD(n=25):received Inj.Ropivacaine(0.25%)+Inj. Dexmedetomidine(1μg/kg) total volume 20 ml was deposited intra-articularly.Patients were monitored in the postoperative ward for the hemodynamic parameters and their Sedation score was assessed.. The efficacy of the drug was determined by improvement in VAS score, duration of analgesia and total number of rescue analgesics during 24 hr in post operative period.
Results: There was no statistically significant differences observed in heart rate except changes at 6 and 8 hr. At 6 and 8 hr in group P pulse (82.48 ± 7.49, 81.44 ± 8.78) as compared to group D (75.38 ± 6.52, 74.96 ± 5.70),because of duration of action of ropivacaine with or without dexmedetomidine.There was no statistically significant difference in blood pressure was found, except at 12 hour and 24 hour (p=0.018), because of longer duration of action of intrarticular dexmedetomidine with ropivacaine in group D.At 6 hrs patients in Group P had a mean VAS score of 3.2 as compared to VAS score values of 1.8 in Group D which is statistically significant..At 2 , 4, 6 and 8 hour VAS score in P group was 1.64, 2.44, 3.24, 2.84 respectively. As compared to group P, in group D VAS score at 2, 4, 6 and 8 hour was 0.92, 1.04, 1.79 and 2.08 respectively. So VAS score lower in group D as compared to group P at 2, 4, 6 and 8 hrs.
A Prospective comparative study of Local anaesthesia & Spinal anaesthesia for...iosrjce
IOSR Journal of Dental and Medical Sciences is one of the speciality Journal in Dental Science and Medical Science published by International Organization of Scientific Research (IOSR). The Journal publishes papers of the highest scientific merit and widest possible scope work in all areas related to medical and dental science. The Journal welcome review articles, leading medical and clinical research articles, technical notes, case reports and others.
PowerPoint. Nonradioactive iodine competes with radioactive iodine. This has implications for the use of recombinant human TSH (rhTSH) when preparing differentiated thyroid cancer patients for radioiodine scanning with continued levothyroxine, because the latter contains iodine.
Evaluation of Effect of Low Dose Fentanyl, Dexmedetomidine and Clonidine in S...iosrjce
In the present study effect of intrathecal hyperbaric Bupivacaine 0.5% with low doses of Clonidine
or Fentanyl or Dexmedetomidine were compared in elective lower abdominal surgeries. This was a prospective
randomized control trial. 90 patients belonging to ASA 1 &II, aged between 20-50 years were allocated into
three groups. Group-C: Clonidine 30µg, Group-D: Dexmedetomidine 5 µg, Group-F: Fentanyl 25 µg. The
onset of sensory blockade was comparable in all the three groups. The onset of motor blockade was earlier by
about 1.3 mins in Dexmedetomidine group when compared to Clonidine and Fentanyl group. Duration of
sensory blockade was prolonged in Dexmedetomidine group (346mins) when compared to Clonidine (300mins)
and Fentanyl (302mins) group. Time duration of motor blockade was prolonged in Dexmedetomidine group
(269mins) when compared to Clonidine (223mins) and Fentanyl (220mins) group. The haemodynamic
parameters were clinically and statistically insignificant The time of first request for analgesics by the patients
was more in Dexmedetomidine group (250mins) when compared to Clonidine (194mins) and Fentanyl
(189mins) group. The use of intrathecal Dexmedetomidine as an adjuvant to Bupivacaine is an attractive
alternative to Fentanyl or Clonidine for long duration surgical procedures due to its profound intrathecal
anesthetic and analgesic properties combined with minimal side effects.
Comparison between Tramadol and Nalbuphine As an Adjunct to Midazolam for Con...iosrjce
IOSR Journal of Dental and Medical Sciences is one of the speciality Journal in Dental Science and Medical Science published by International Organization of Scientific Research (IOSR). The Journal publishes papers of the highest scientific merit and widest possible scope work in all areas related to medical and dental science. The Journal welcome review articles, leading medical and clinical research articles, technical notes, case reports and others.
To Evaluate the Role of Inj. Ketamine (0.3mg/Kg) Intravenously, Before Skin I...iosrjce
IOSR Journal of Dental and Medical Sciences is one of the speciality Journal in Dental Science and Medical Science published by International Organization of Scientific Research (IOSR). The Journal publishes papers of the highest scientific merit and widest possible scope work in all areas related to medical and dental science. The Journal welcome review articles, leading medical and clinical research articles, technical notes, case reports and others.
Prospective Randomized Double-Blind Study of Effectiveness of Dexmedetomidine...asclepiuspdfs
Introduction: Laryngoscopy and endotracheal intubation is associated with transient increase in heart rate (HR) and arterial blood pressure due to the sympathoadrenal stimulation. It can produce deleterious effects in patients with cardiovascular and cerebrovascular disease, in the form of myocardial ischemia, pulmonary edema, and cerebral hemorrhage. Dexmedetomidine has been effective in blunting the hemodynamic response to laryngoscopy and tracheal intubation. In this study, we used dexmedetomidine in pre-operative intravenous infusion dose of 1 mcg/kg over 20 min before induction. Aims and Objectives: The aim of the study was to study the efficacy and safety of dexmedetomidine on attenuation of pressor response during laryngoscopy and tracheal intubation, w.r.t. (1) pressor response during laryngoscopy and tracheal intubation, (2) hemodynamic stability, and (3) any adverse effects.
Antiemetic Prophylaxis in Major Gynaecological Surgery With Intravenous Grani...inventionjournals
In a prospective double blind randomized study we evaluated the prophylactic anti emetic efficacy of granisetron, a 5HT3 receptor antagonist and metoclopramide, a benzamide anti emetic on postoperative nausea and vomiting after major gynaecological surgery under general anaesthesia. The patients received a single dose of granisetron, 40mcg/kg (Group A, n = 25) or metoclopramide, 0.15mg/kg (Group B, n = 25) before induction of anaesthesia in a coded syringe. The response was assessed during 0-4 hrs, 4-8 hrs, 8-16hrs and 16-24 hrs time intervals after recovery from anaesthesia by means of presence or absence of nausea, retching or vomiting. The overall control of PONV during early postoperative period (0-4 hrs) did not show statistically significant differences after administration of either drug. The incidence of PONV during the next 20 hours was 12% and 48% with Group A (Granisetron) and Group B (Metoclopramide) respectively. Nausea scores are significantly lower in-group A (Granisetron) than in Group B (Metoclopramide) in all the four assessment periods. Although there were no emetic episodes in the granisetron group, 32% of patients in metoclopramide group were observed to have such episodes during the assessment periods. (P value< 0.05). No clinically important adverse events due to drugs were observed in any of the groups. In conclusion, the prophylactic use of granisetron is more effective and superior to metoclopramide in preventing postoperative nausea and vomiting in patients under going major gynaecological surgery under general anaesthesia.
Antiemetic Prophylaxis in Major Gynaecological Surgery With Intravenous Grani...inventionjournals
In a prospective double blind randomized study we evaluated the prophylactic anti emetic efficacy of granisetron, a 5HT3 receptor antagonist and metoclopramide, a benzamide anti emetic on postoperative nausea and vomiting after major gynaecological surgery under general anaesthesia. The patients received a single dose of granisetron, 40mcg/kg (Group A, n = 25) or metoclopramide, 0.15mg/kg (Group B, n = 25) before induction of anaesthesia in a coded syringe. The response was assessed during 0-4 hrs, 4-8 hrs, 8-16hrs and 16-24 hrs time intervals after recovery from anaesthesia by means of presence or absence of nausea, retching or vomiting. The overall control of PONV during early postoperative period (0-4 hrs) did not show statistically significant differences after administration of either drug. The incidence of PONV during the next 20 hours was 12% and 48% with Group A (Granisetron) and Group B (Metoclopramide) respectively. Nausea scores are significantly lower in-group A (Granisetron) than in Group B (Metoclopramide) in all the four assessment periods. Although there were no emetic episodes in the granisetron group, 32% of patients in metoclopramide group were observed to have such episodes during the assessment periods. (P value< 0.05). No clinically important adverse events due to drugs were observed in any of the groups. In conclusion, the prophylactic use of granisetron is more effective and superior to metoclopramide in preventing postoperative nausea and vomiting in patients under going major gynaecological surgery under general anaesthesia.
“A Comparative Study of Bupivacaine with Dexamethasone and Bupivacaine with C...iosrjce
IOSR Journal of Dental and Medical Sciences is one of the speciality Journal in Dental Science and Medical Science published by International Organization of Scientific Research (IOSR). The Journal publishes papers of the highest scientific merit and widest possible scope work in all areas related to medical and dental science. The Journal welcome review articles, leading medical and clinical research articles, technical notes, case reports and others.
Comparison between Tramadol and Nalbuphine As an Adjunct to Midazolam for Con...iosrjce
IOSR Journal of Dental and Medical Sciences is one of the speciality Journal in Dental Science and Medical Science published by International Organization of Scientific Research (IOSR). The Journal publishes papers of the highest scientific merit and widest possible scope work in all areas related to medical and dental science. The Journal welcome review articles, leading medical and clinical research articles, technical notes, case reports and others.
To Evaluate the Role of Inj. Ketamine (0.3mg/Kg) Intravenously, Before Skin I...iosrjce
IOSR Journal of Dental and Medical Sciences is one of the speciality Journal in Dental Science and Medical Science published by International Organization of Scientific Research (IOSR). The Journal publishes papers of the highest scientific merit and widest possible scope work in all areas related to medical and dental science. The Journal welcome review articles, leading medical and clinical research articles, technical notes, case reports and others.
Prospective Randomized Double-Blind Study of Effectiveness of Dexmedetomidine...asclepiuspdfs
Introduction: Laryngoscopy and endotracheal intubation is associated with transient increase in heart rate (HR) and arterial blood pressure due to the sympathoadrenal stimulation. It can produce deleterious effects in patients with cardiovascular and cerebrovascular disease, in the form of myocardial ischemia, pulmonary edema, and cerebral hemorrhage. Dexmedetomidine has been effective in blunting the hemodynamic response to laryngoscopy and tracheal intubation. In this study, we used dexmedetomidine in pre-operative intravenous infusion dose of 1 mcg/kg over 20 min before induction. Aims and Objectives: The aim of the study was to study the efficacy and safety of dexmedetomidine on attenuation of pressor response during laryngoscopy and tracheal intubation, w.r.t. (1) pressor response during laryngoscopy and tracheal intubation, (2) hemodynamic stability, and (3) any adverse effects.
Antiemetic Prophylaxis in Major Gynaecological Surgery With Intravenous Grani...inventionjournals
In a prospective double blind randomized study we evaluated the prophylactic anti emetic efficacy of granisetron, a 5HT3 receptor antagonist and metoclopramide, a benzamide anti emetic on postoperative nausea and vomiting after major gynaecological surgery under general anaesthesia. The patients received a single dose of granisetron, 40mcg/kg (Group A, n = 25) or metoclopramide, 0.15mg/kg (Group B, n = 25) before induction of anaesthesia in a coded syringe. The response was assessed during 0-4 hrs, 4-8 hrs, 8-16hrs and 16-24 hrs time intervals after recovery from anaesthesia by means of presence or absence of nausea, retching or vomiting. The overall control of PONV during early postoperative period (0-4 hrs) did not show statistically significant differences after administration of either drug. The incidence of PONV during the next 20 hours was 12% and 48% with Group A (Granisetron) and Group B (Metoclopramide) respectively. Nausea scores are significantly lower in-group A (Granisetron) than in Group B (Metoclopramide) in all the four assessment periods. Although there were no emetic episodes in the granisetron group, 32% of patients in metoclopramide group were observed to have such episodes during the assessment periods. (P value< 0.05). No clinically important adverse events due to drugs were observed in any of the groups. In conclusion, the prophylactic use of granisetron is more effective and superior to metoclopramide in preventing postoperative nausea and vomiting in patients under going major gynaecological surgery under general anaesthesia.
Antiemetic Prophylaxis in Major Gynaecological Surgery With Intravenous Grani...inventionjournals
In a prospective double blind randomized study we evaluated the prophylactic anti emetic efficacy of granisetron, a 5HT3 receptor antagonist and metoclopramide, a benzamide anti emetic on postoperative nausea and vomiting after major gynaecological surgery under general anaesthesia. The patients received a single dose of granisetron, 40mcg/kg (Group A, n = 25) or metoclopramide, 0.15mg/kg (Group B, n = 25) before induction of anaesthesia in a coded syringe. The response was assessed during 0-4 hrs, 4-8 hrs, 8-16hrs and 16-24 hrs time intervals after recovery from anaesthesia by means of presence or absence of nausea, retching or vomiting. The overall control of PONV during early postoperative period (0-4 hrs) did not show statistically significant differences after administration of either drug. The incidence of PONV during the next 20 hours was 12% and 48% with Group A (Granisetron) and Group B (Metoclopramide) respectively. Nausea scores are significantly lower in-group A (Granisetron) than in Group B (Metoclopramide) in all the four assessment periods. Although there were no emetic episodes in the granisetron group, 32% of patients in metoclopramide group were observed to have such episodes during the assessment periods. (P value< 0.05). No clinically important adverse events due to drugs were observed in any of the groups. In conclusion, the prophylactic use of granisetron is more effective and superior to metoclopramide in preventing postoperative nausea and vomiting in patients under going major gynaecological surgery under general anaesthesia.
“A Comparative Study of Bupivacaine with Dexamethasone and Bupivacaine with C...iosrjce
IOSR Journal of Dental and Medical Sciences is one of the speciality Journal in Dental Science and Medical Science published by International Organization of Scientific Research (IOSR). The Journal publishes papers of the highest scientific merit and widest possible scope work in all areas related to medical and dental science. The Journal welcome review articles, leading medical and clinical research articles, technical notes, case reports and others.
Nora e reversal colorato slideshare; NaPoli i SIA 2016Claudio Melloni
Non operating room anesthesia and reversal of muscle relaxation.Respiratory complications due to residual paralysis.Mechanism of action of residual paralysis .Sugammadex.Calabadion New discoveries.
Valut az rischio anest sia napoli dic 2008;italian + bibliografyClaudio Melloni
evaluation of operative risk for non cardiac surgery ;for anesthesia and surgery.Cardiac conditions,including heart failure ,use of betablockers,stains.Diabetes risk,including difficult intubation.Thromboembolic risk,
lowest heart rate
lowest mean arterial pressure
estimated blood loss
A score built from these 3 predictors has proved strongly predictive of the risk of major postoperative complications and death in general and vascular surgery
A new dantrolene formulation for the treatment of Malignant hyperthermia(MH).Receptors,pharmacokinetics,dosages,preparation of dantrolene,practical tips,advantages.
The Gram stain is a fundamental technique in microbiology used to classify bacteria based on their cell wall structure. It provides a quick and simple method to distinguish between Gram-positive and Gram-negative bacteria, which have different susceptibilities to antibiotics
Title: Sense of Taste
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the structure and function of taste buds.
Describe the relationship between the taste threshold and taste index of common substances.
Explain the chemical basis and signal transduction of taste perception for each type of primary taste sensation.
Recognize different abnormalities of taste perception and their causes.
Key Topics:
Significance of Taste Sensation:
Differentiation between pleasant and harmful food
Influence on behavior
Selection of food based on metabolic needs
Receptors of Taste:
Taste buds on the tongue
Influence of sense of smell, texture of food, and pain stimulation (e.g., by pepper)
Primary and Secondary Taste Sensations:
Primary taste sensations: Sweet, Sour, Salty, Bitter, Umami
Chemical basis and signal transduction mechanisms for each taste
Taste Threshold and Index:
Taste threshold values for Sweet (sucrose), Salty (NaCl), Sour (HCl), and Bitter (Quinine)
Taste index relationship: Inversely proportional to taste threshold
Taste Blindness:
Inability to taste certain substances, particularly thiourea compounds
Example: Phenylthiocarbamide
Structure and Function of Taste Buds:
Composition: Epithelial cells, Sustentacular/Supporting cells, Taste cells, Basal cells
Features: Taste pores, Taste hairs/microvilli, and Taste nerve fibers
Location of Taste Buds:
Found in papillae of the tongue (Fungiform, Circumvallate, Foliate)
Also present on the palate, tonsillar pillars, epiglottis, and proximal esophagus
Mechanism of Taste Stimulation:
Interaction of taste substances with receptors on microvilli
Signal transduction pathways for Umami, Sweet, Bitter, Sour, and Salty tastes
Taste Sensitivity and Adaptation:
Decrease in sensitivity with age
Rapid adaptation of taste sensation
Role of Saliva in Taste:
Dissolution of tastants to reach receptors
Washing away the stimulus
Taste Preferences and Aversions:
Mechanisms behind taste preference and aversion
Influence of receptors and neural pathways
Impact of Sensory Nerve Damage:
Degeneration of taste buds if the sensory nerve fiber is cut
Abnormalities of Taste Detection:
Conditions: Ageusia, Hypogeusia, Dysgeusia (parageusia)
Causes: Nerve damage, neurological disorders, infections, poor oral hygiene, adverse drug effects, deficiencies, aging, tobacco use, altered neurotransmitter levels
Neurotransmitters and Taste Threshold:
Effects of serotonin (5-HT) and norepinephrine (NE) on taste sensitivity
Supertasters:
25% of the population with heightened sensitivity to taste, especially bitterness
Increased number of fungiform papillae
New Drug Discovery and Development .....NEHA GUPTA
The "New Drug Discovery and Development" process involves the identification, design, testing, and manufacturing of novel pharmaceutical compounds with the aim of introducing new and improved treatments for various medical conditions. This comprehensive endeavor encompasses various stages, including target identification, preclinical studies, clinical trials, regulatory approval, and post-market surveillance. It involves multidisciplinary collaboration among scientists, researchers, clinicians, regulatory experts, and pharmaceutical companies to bring innovative therapies to market and address unmet medical needs.
Tom Selleck Health: A Comprehensive Look at the Iconic Actor’s Wellness Journeygreendigital
Tom Selleck, an enduring figure in Hollywood. has captivated audiences for decades with his rugged charm, iconic moustache. and memorable roles in television and film. From his breakout role as Thomas Magnum in Magnum P.I. to his current portrayal of Frank Reagan in Blue Bloods. Selleck's career has spanned over 50 years. But beyond his professional achievements. fans have often been curious about Tom Selleck Health. especially as he has aged in the public eye.
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Introduction
Many have been interested in Tom Selleck health. not only because of his enduring presence on screen but also because of the challenges. and lifestyle choices he has faced and made over the years. This article delves into the various aspects of Tom Selleck health. exploring his fitness regimen, diet, mental health. and the challenges he has encountered as he ages. We'll look at how he maintains his well-being. the health issues he has faced, and his approach to ageing .
Early Life and Career
Childhood and Athletic Beginnings
Tom Selleck was born on January 29, 1945, in Detroit, Michigan, and grew up in Sherman Oaks, California. From an early age, he was involved in sports, particularly basketball. which played a significant role in his physical development. His athletic pursuits continued into college. where he attended the University of Southern California (USC) on a basketball scholarship. This early involvement in sports laid a strong foundation for his physical health and disciplined lifestyle.
Transition to Acting
Selleck's transition from an athlete to an actor came with its physical demands. His first significant role in "Magnum P.I." required him to perform various stunts and maintain a fit appearance. This role, which he played from 1980 to 1988. necessitated a rigorous fitness routine to meet the show's demands. setting the stage for his long-term commitment to health and wellness.
Fitness Regimen
Workout Routine
Tom Selleck health and fitness regimen has evolved. adapting to his changing roles and age. During his "Magnum, P.I." days. Selleck's workouts were intense and focused on building and maintaining muscle mass. His routine included weightlifting, cardiovascular exercises. and specific training for the stunts he performed on the show.
Selleck adjusted his fitness routine as he aged to suit his body's needs. Today, his workouts focus on maintaining flexibility, strength, and cardiovascular health. He incorporates low-impact exercises such as swimming, walking, and light weightlifting. This balanced approach helps him stay fit without putting undue strain on his joints and muscles.
Importance of Flexibility and Mobility
In recent years, Selleck has emphasized the importance of flexibility and mobility in his fitness regimen. Understanding the natural decline in muscle mass and joint flexibility with age. he includes stretching and yoga in his routine. These practices help prevent injuries, improve posture, and maintain mobilit
ARTIFICIAL INTELLIGENCE IN HEALTHCARE.pdfAnujkumaranit
Artificial intelligence (AI) refers to the simulation of human intelligence processes by machines, especially computer systems. It encompasses tasks such as learning, reasoning, problem-solving, perception, and language understanding. AI technologies are revolutionizing various fields, from healthcare to finance, by enabling machines to perform tasks that typically require human intelligence.
Explore natural remedies for syphilis treatment in Singapore. Discover alternative therapies, herbal remedies, and lifestyle changes that may complement conventional treatments. Learn about holistic approaches to managing syphilis symptoms and supporting overall health.
NVBDCP.pptx Nation vector borne disease control programSapna Thakur
NVBDCP was launched in 2003-2004 . Vector-Borne Disease: Disease that results from an infection transmitted to humans and other animals by blood-feeding arthropods, such as mosquitoes, ticks, and fleas. Examples of vector-borne diseases include Dengue fever, West Nile Virus, Lyme disease, and malaria.
Recomendações da OMS sobre cuidados maternos e neonatais para uma experiência pós-natal positiva.
Em consonância com os ODS – Objetivos do Desenvolvimento Sustentável e a Estratégia Global para a Saúde das Mulheres, Crianças e Adolescentes, e aplicando uma abordagem baseada nos direitos humanos, os esforços de cuidados pós-natais devem expandir-se para além da cobertura e da simples sobrevivência, de modo a incluir cuidados de qualidade.
Estas diretrizes visam melhorar a qualidade dos cuidados pós-natais essenciais e de rotina prestados às mulheres e aos recém-nascidos, com o objetivo final de melhorar a saúde e o bem-estar materno e neonatal.
Uma “experiência pós-natal positiva” é um resultado importante para todas as mulheres que dão à luz e para os seus recém-nascidos, estabelecendo as bases para a melhoria da saúde e do bem-estar a curto e longo prazo. Uma experiência pós-natal positiva é definida como aquela em que as mulheres, pessoas que gestam, os recém-nascidos, os casais, os pais, os cuidadores e as famílias recebem informação consistente, garantia e apoio de profissionais de saúde motivados; e onde um sistema de saúde flexível e com recursos reconheça as necessidades das mulheres e dos bebês e respeite o seu contexto cultural.
Estas diretrizes consolidadas apresentam algumas recomendações novas e já bem fundamentadas sobre cuidados pós-natais de rotina para mulheres e neonatos que recebem cuidados no pós-parto em unidades de saúde ou na comunidade, independentemente dos recursos disponíveis.
É fornecido um conjunto abrangente de recomendações para cuidados durante o período puerperal, com ênfase nos cuidados essenciais que todas as mulheres e recém-nascidos devem receber, e com a devida atenção à qualidade dos cuidados; isto é, a entrega e a experiência do cuidado recebido. Estas diretrizes atualizam e ampliam as recomendações da OMS de 2014 sobre cuidados pós-natais da mãe e do recém-nascido e complementam as atuais diretrizes da OMS sobre a gestão de complicações pós-natais.
O estabelecimento da amamentação e o manejo das principais intercorrências é contemplada.
Recomendamos muito.
Vamos discutir essas recomendações no nosso curso de pós-graduação em Aleitamento no Instituto Ciclos.
Esta publicação só está disponível em inglês até o momento.
Prof. Marcus Renato de Carvalho
www.agostodourado.com
Basavarajeeyam is an important text for ayurvedic physician belonging to andhra pradehs. It is a popular compendium in various parts of our country as well as in andhra pradesh. The content of the text was presented in sanskrit and telugu language (Bilingual). One of the most famous book in ayurvedic pharmaceutics and therapeutics. This book contains 25 chapters called as prakaranas. Many rasaoushadis were explained, pioneer of dhatu druti, nadi pareeksha, mutra pareeksha etc. Belongs to the period of 15-16 century. New diseases like upadamsha, phiranga rogas are explained.
1. La lidocaina come anestetico
locale nella chirurgia del contorno
corporeo
Il punto di vista dell’anestesista
Claudio Melloni
libero professionista
Consulente di anestesia: Villa Torri,Bologna;Villa
Chiara,Bologna,Poliambulatorio Gynepro,Bologna
2. Dosaggi di lidocaina nella tecnica
tumescente
Klein JA.Tumescent technique for regional anesthesia
permits lidocaine doses of 35 mg/kg for liposuction. J.
Dermatol. Surg. Oncol. 16: 248, 1990.
Lillis PJ. Liposuction surgery under local anesthesia: Limited
blood loss and minimal lidocaine absorption. J. Dermatol.
Surg. Oncol. 14: 1145, 1988. cita 88 mg/kg come sicuro
Coleman WP. Tumescent anesthesia with a lidocaine dose
of 55 mg/kg is safe for liposuction. Dermatol. Surg. 22:
919, 1996
3. Lillis, P. J. Liposuction surgery under local anesthesia: Limited
blood loss and minimal lidocaine absorption. J. Dermatol. Surg.
Oncol. 14: 1145, 1988
measured serum lidocaine concentrations in 20
patients after suction lipectomy with the tumescent
technique.
Total lidocaine dose ranged between
2000 mg and 5600 mg.
Blood samples drawn 15, 30, and 60 minutes
after infiltration revealed lidocaine concentrations
<1.7 µg/ml in all cases.
No signs of toxicity were reported.
4. Come mai tali dosaggi di lidocaina sono stati
tollerati?
NON si sa
Ipotesi
l’assorbimento dal tessuto sotto cutaneo e adiposo è
molto lento
vascolarizzazione scarsa
adrenalina lo riduce ulteriormente,impedendo così il raggiungimento di livelli plasmatici
tossici
la successiva suzione asporta una discreta quota del farmaco
infiltrato contribuendo alla sicurezza.I dati disponibili indicano una quota di
rimossione della lido infiltrata variabile dal 10% al 31%
» Kenkel JM,Lipschitz , A H,Shepherd G,Armstrong VW,Streit F,Oellerich M, Luby M, Rohrich
R,Brown SA.D.Pharmacokinetics and Safety of Lidocaine and Monoethylglycinexylidide in
Liposuction: A Microdialysis Study.J Plast Surg . 114,2004, 516-524.
» Hagerty T,Klein, P. Fat partitioning of lidocaine in tumescent liposuction. Ann. Plast. Surg.
42: 372,1999.
5. Dosaggio massimo di lidocaina
Il dosaggio massimo raccomandato in
letteratura è di 7 mg/kg U.S. Food and Drug
Administration and manufacturers.
» Lidocaine hydrochloride package insert. Astra Pharmaceutical Products, 1995.
Per infiltrazione:4,5 mg/kg and 6 mg/kg
+adr(Goodman Gillman,the Pharmacological basis of Therapeutics)
200 mg o 500 mg se associata a
adrenalina:Guida all’Uso dei farmaci
300 mg o 500 mg + adr:Cousins, Neural
Blockade.,Lippincott Ed.
6. Pressione di infiltrazione s.c.
la pressione alla quale si effettua la
iniezione (Alta Max press tissutale durante iniezione
339 +/- 63 mmHg vs bassa pressione 27 +/- 9 mmHg)
non ha effetti sulla curva di
assorbimento………
» Rubin JP, Bierman C, Rosow CE, Arthur GR, Chang Y,
Courtiss EH, May JW Jr.The tumescent technique: the effect
of high tissue pressure and dilute epinephrine on absorption
of lidocainePlast Reconstr Surg. 1999 Mar;103(3):990-6;.
» Termpo di infiltrazione :16 min con alta pressione vs
20 con bassa
7. Velocità di infiltrazione
27 mg/min o 200 mg/min di lidocaina
diluita e con epinefrina non
determinano differenti livelli plasmatici
di lidocaina( nelle prime 2 h)
Butterwick KJ, Goldman MP, Sriprachya-Anunt S. Lidocaine
levels during the first two hours of infiltration of dilute
anesthetic solution for tumescent liposuction: rapid versus
slow delivery .Dermatol Surg. 1999 Sep;25(9):681-5.
Aghi spinali e cannule sottili multiorifizi
9. Livelli plasmatici in arteria dopo iniezione ev
rapida o lenta di lidocaina
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10. Concentrazioni plasmatiche di lidocaina dopo iniezione in 4
sedi differenti
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11. Concentrazioni plasmatiche di lidocaina e prilocaina dopo 400
mg inietttati per via peridurale
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12. Livelli plasmatici di lidocaina in un paziente dopo
sgonfiaggio della cuffia ( anestesia endovenosa con 3 mg/kg
di lidocaina 0.5% e 45 min di applicazione del
tourniquet).Tucker GT,Boas RA. Pharmacokinetic aspects of intravenous regional
anesthetics.Anesthesiology 1971;34:578.
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13. Accumulo locale e sistemico di lidocaina dopo bolo
peridurale per anestesia e infusione continua per analgesia
postop.da Holmdahl MH et al.Clinical aspects of continuous epidural blockade for postoperative pain
relief.Ups.J.Med.Sci.77,47:1972.
Infusione cont.
bolo
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14. Lidocaine plasma concentration over time for each experimental group
(±SEM). In the two groups with epinephrine, the time to maximal lidocaine concentration (Tmax) was 11 hours
after injection, whereas Tmax was reached in 3.4 hours in the groups without epinephrine (p < 0.001). Rubin JP
, Bierman C, Rosow CE, Arthur GR, Chang Y, Courtiss EH, May JW Jr.The tumescent technique: the effect of
high tissue pressure and dilute epinephrine on absorption of lidocainePlast Reconstr Surg. 1999
Mar;103(3):990-6
Lido 0.1 con epinefr 1:1.000.000 s.c.
faccia lat della coscia;no lipectomia
Senza adr.
Con adr.
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15. Rubin JP, Xie Z, Davidson C, Rosow CE
, Chang Y, May JW Jr.Rapid absorption
of tumescent lidocaine above the
clavicles: a prospective clinical study.
Plast Reconstr Surg. 2005;115:1744-51.
16. Concentrazioni plasmatiche di lidocaina dopo tumescenza a
livello del collo o della coscia.. Time to reach maximal lidocaine
concentration was 5.8 hours after neck injection and 12.0 hours after thigh
injection (p 0.00Rubin JP, Xie Z, Davidson C, Rosow CE, Chang Y, May JW Jr.Rapid absorption of tumescent
lidocaine above the clavicles: a prospective clinical study. Plast Reconstr Surg. 2005;115:1744-51
neck
thigh
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.
17. Curve di assorbimento della tumescenza con
lidocaina con simulazione in caso di infiltrazione
simultaneaRubin JP, Xie Z, Davidson C, Rosow CE, Chang Y, May JW Jr.Rapid absorption of
tumescent lidocaine above the clavicles: a prospective clinical study. Plast Reconstr Surg. 2005;115:1744-51.
additiva
collo
coscia
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18. Ma non si tratta solo di
lidocaina............
La MEGX è un metabolita
attivo
19. Plasma Concentrations of Monoethylglycinexylidide during
and after Breast Augmentation Rygnestad, T, Samdal F.Plast reconstruct Surg 2000
106:728-31. The plasma concentration of monoethylglycinexylidide
(MEGX; microgams per milliliter) versus the time after the end
of the injection..
A total dose of 825 to 1280 mg of 0.2% and 0.5% lidocaine with
epinephrine corresponding to 16.3 to 21.8 mg/kg (mean 18.2 mg/kg)
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20. The plasma concentration of MEGX +lidocaine (micrograms
per milliliter) versus the time after the end of the injection
Plasma Concentrations of Monoethylglycinexylidide during and after Breast Augmentation
Rygnestad, T, Samdal F.Plast reconstruct Surg 2000 106:728-31
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
21. Tempo di raggiungimento dei livelli massimi di lido e megx
dopo infiltrazione per tumescenza :Kenkel JM,Lipschitz , A H,Shepherd
G,Armstrong VW,Streit F,Oellerich M, Luby M, Rohrich
R,Brown SA.D.Pharmacokinetics and Safety of Lidocaine and Monoethylglycinexylidide in Liposuction: A
Microdialysis Study.J Plast Surg . 114,2004, 516-524
dose media di lido 22 mg/kg
22. Livelli plasmatci massimi di lidocaina e megx dopo infiltrazione
per tumescenza:dose media di lido 22 mg/kgKenkel JM,Lipschitz , A
H,Shepherd G,Armstrong VW,Streit F,Oellerich M, Luby M, Rohrich R,Brown SA.D.Pharmacokinetics and
Safety of Lidocaine and Monoethylglycinexylidide in Liposuction: A Microdialysis Study.J Plast Surg .
114,2004, 516-524
23. Kenkel JM,Lipschitz , A H,Shepherd G,Armstrong VW,Streit
F,Oellerich M, Luby M, Rohrich R,Brown SA.D.Pharmacokinetics and
Safety of Lidocaine and Monoethylglycinexylidide in Liposuction: A
Microdialysis Study.J Plast Surg . 114,2004, 516-524
absorbed lidocaine was estimated to be 1197.7 mg
(range, 911.0 to 1596.0 mg).: 64 percent (range, 45
to 93 percent) of the infiltrated dose was ultimately
absorbed.
Lipoaspirate analysis showed that 178.1 mg of
lidocaine (range, 154 to 204 mg), 9.8 percent
(range, 9.1 to 10.8 percent) of the infiltrated
dose was removed during the procedure.
24. Mean plasma concentration of lidocaine (lido),
monoethylglycinexylidide (MEGX), and lidocaine plus
monoethylglycinexylidide vs time (mean, SEM). Kenkel JM,Lipschitz , A
H,Shepherd G,Armstrong VW,Streit F,Oellerich M, Luby M, Rohrich R,Brown SA.D.Pharmacokinetics
and Safety of Lidocaine and Monoethylglycinexylidide in Liposuction: A Microdialysis Study.J Plast
Surg . 114,2004, 516-524
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
25. Dove va a finire la lidocaina che
non è nel plasma?
10% (range, 9.1 to 10.8)rimossa durante intervento
» Kenkel JM,Lipschitz , A H,Shepherd G,Armstrong VW,Streit F,Oellerich M, Luby M,
Rohrich R,Brown SA.D.Pharmacokinetics and Safety of Lidocaine and
Monoethylglycinexylidide in Liposuction: A Microdialysis Study.J Plast Surg .
114,2004, 516-524:
31% aspirato
nel grasso rimosso o rimasto: rapporto grasso / liquido 1.3- 2.95
Hagerty, T., and Klein, P. Fat partitioning of lidocaine in tumescent liposuction. Ann.
Plast. Surg. 42: 372,1999.
Hardy, S. P., Ortiz-Colberg, R., and Poquette, M. A. Re: Fat
partitioning of lidocaine in tumescent liposuction. Ann. Plast. Surg.
43: 574, 1999.
26. Importanza del legame alle proteine
plasmatiche
Lidocaina + lipofilica del MEGX e + legata alla 1acid glycoprotein,:60 to 70 %v s 15% for MEGX
La parte attiva di un farmaco è quella libera
Sebbene i livelli di MEGX siano sostanzialmente +
bassi di quelli della lido,la concentrazione della MEGX
libera è relativamente + alta e potrebbe determinare
un ruolo maggiore nella tox.......
27. Anaesthesist. 2007 Aug;56(8):785-9. Links
[Tumescent anaesthesia for dermatological
surgery. Plasma concentrations of lidocaine and
prilocaine]
[Article in German]
Rudlof K, Rüffert H, Wehner M, Wetzig T, Eichhorn
K, Olthoff D.
Klinik und Poliklinik für Anästhesiologie und
Intensivtherapie, Universitätsklinikum Leipzig AöR,
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
28. Nordström H, Stånge K. Plasma lidocaine levels and risks
after liposuction with tumescent anaesthesia. Acta
Anaesthesiol Scand. 2005 Nov;49(10):1487-90.
35 mg per kg bodyweight of lidocaine for abdominal
liposuction.
3 lt of buffered solution of 0.08% lidocaine with epinephrine
was infiltrated subcutaneously over the abdomen in 8 female
patients at a rate of 116 ml/min
monitored intravenous (i.v.) light sedation.
Plasma levels of lidocaine and signs of subjective and
objective symptoms were recorded every 3 h for 20 h after
liposuction.
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
29. RESULTS of
Plasma lidocaine levels and risks after liposuction with
tumescent anaesthesia. Acta Anaesthesiol Scand. 2005
Nov;49(10):1487-90. :
Peak plasma levels (2.3 +/- 0.63 microg/ml) of lidocaine occurred after
5-17 h.
No correlation was found between peak levels and dose per kg
bodyweight or total amount of lidocaine infiltrated.
One patient experienced tinnitus after 14 h when a plasma level of 3.3
microg/ml was recorded.
CONCLUSION: Doses of lidocaine up to 35 mg/kg were sufficient for
abdominal liposuction using the tumescent technique and gave no
fluid overload or toxic symptoms in eight patients, but with this dose
there is still a risk of subjective symptoms in association with the peak
level of lidocaine that may appear after discharge.
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30. Conclusioni dalla letteratura
citata
Ci sono significative differenze interindividuali nei
livelli plasmatici di lidocaina
Il picco del livello plasmatico di lidocaina si raggiunge
assai tardivamente
Anche la MEGX picca tardivamente
I 2 farmaci sommano la tox...................
Ci sono altri problemi che complicano il quadro.........
31. Pazienti a rischio di tox della
lidocaina
Riduzione di flusso epatico
:insuff epatica .....
CHF: MEGX / lido
» Halkin, H., Meffin, P., Melmon, K. L., et al. Influence of congestive heart
failure on blood vessels of lidocaine and its active monodeethylated
metabolite. Clin. Pharmacol. Ther. 17: 669, 1975.
33. Lo stress altera i livelli
plasmatici di lidocaina
Eur J Drug Metab Pharmacokinet. 2002 Oct-Dec;27(4):229-32. Links
Stress-induced lidocaine modification in serum and tissues.
Saranteas T, Tesseromatis C, Potamianou A, Mourouzis C, Varonos D.
influence of acute (trauma) and chronic (cold swimming and adjuvant
rheumatoid arthritis) stress on lidocaine concentrations in plasma.
Forty male Wistar rats were used. The animals were divided into four
groups. Group A served as control. Group B underwent mandible
osteotomy. Group C was submitted to swimming stress in cold water
4 degrees C for ten minutes daily for 15 minutes, while group D
underwent experimental arthritis with Freud's adjuvant. All groups
received lidocaine i.m (2.5 mg/kg). Blood samples were collected and
FFA (free fatty acid), unbound-lidocaine, albumin and a1-acid
glycoprotein concentrations were estimated. Furthermore, the
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Anestesia e Rianimazione
adrenals,diheart and liverOspedale di isolated. The adrenals' relative weight
were Faenza(RA)
35. Ma La lidocaina tissutale residua
contribuisce alla analgesia
postoperatoria?
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36. Livelli tissutali di lidocaina
Kenkel JM,Lipschitz , A H,Shepherd G,Armstrong VW,Streit F,Oellerich M, Luby M, Rohrich R,Brown
SA.D.Pharmacokinetics and Safety of Lidocaine and Monoethylglycinexylidide in Liposuction: A
Microdialysis Study.J Plast Surg . 114,2004, 516-524
Regione mammaria
Peak local tissue concentrations of lidocaine were in the 0- to 4-hour collection, immediately
Area mammaria
postoperatively in both left and right femurs [18.5 (7.89) microg/ml mean (SEM) and
27.7 (13.18)microg/ml, respectively]. Lidocaine levels decreased exponentially from the initial
peak, 4 to 8 hours postoperatively at the infiltrated sites in both left and right femurs
[4.4 (1.83) and 4.3 (4.83) , as the drug was absorbed and redistributed to
tissue distal from the infiltrated sites. In contrast,peak levels in the control probe occurred
in the 8- to 12-hour collection [3.94 (2.4)mirog/ml].
37. Livelli tissutali di lidocaina e
analgesia
Kenkel JM,Lipschitz , A H,Shepherd G,Armstrong VW,Streit F,Oellerich M, Luby M, Rohrich R,Brown
SA.D.Pharmacokinetics and Safety of Lidocaine andMonoethylglycinexylidide in Liposuction: A
Microdialysis Study.J Plast Surg . 114,2004, 516-524
4-5 microg/lt di tessuto
Kopacz and BernardsKopacz, D. J., and Bernards, C. M. Effect of clonidine on
lidocaine clearance in vivo: A microdialysis study in humans. Anesthesiology 95: 1371,
2001.
Bernards, C. M., and Kopacz, D. J. Effect of epinephrine on lidocaine clearance in
vivo: A microdialysis study in humans. Anesthesiology 91: 962, 1999.
25 microg/lt per il pizzicotto
42microg/lt per il tatto
20 microg/lt per il freddo.
.
38. Livelli tessutali di lidocaina
Kenkel JM,Lipschitz , A H,Shepherd G,Armstrong VW,Streit F,Oellerich M,
Luby M, Rohrich R,Brown SA.D.Pharmacokinetics and Safety of Lidocaine
andMonoethylglycinexylidide in Liposuction: A Microdialysis Study.J Plast
Surg . 114,2004, 516-524
I livelli plasmatici di lidocaina vanno a
picco da 8 a 16 h dopo l’intervento e
persistono per 36 h
Ma……….i livelli tissutali di lido sono
subterapeutici già dopo 4 o 8 h
39. Tsai PS, Buerkle ,H, Huang LT, Lee TC,. Yang C, Lee
JHLidocaine Concentrations in Plasma and Cerebrospinal
FluidAfter Systemic Bolus Administration in Humans .Anesth
Analg 1998;87:6014
Preclinical studies suggest that systemic lidocaine acts at the level of the spinal dorsal horn to
inhibit hyperalgesia resulting from nerve injury, yet no clinical data are available to support this
view. Therefore, we sought to characterize the time course of lidocaine in the plasma and
cerebrospinal fluid (CSF) after an IV bolus injection of lidocaine 2 mg/kg in patients scheduled
for surgery involving spinal anesthesia. Sixty-five patients were randomly allocated to one of five
study groups (n = 13 per group) receiving IV lidocaine before CSF/ plasma sampling at 5, 10, 15,
30, or 60 min. Gas chromatographic analysis of these samples revealed a fast but transient peak
(5-15 min) in lidocaine plasma levels (1.7 ? 0.16 pg/mL), which declined rapidly thereafter.
Only small concentrations of IV lidocaine were found in the CSF (6%-8% of plasma
concentration), but this fraction remained stable from 15 min until termination of
the experiment. No statistical correlation was observed between plasma and CSF lidocaine levels.
These data suggest that because of the prolonged availability of lidocaine at the spinal dorsal
horn level, systemic administration of lidocaine suppresses central sensitization within the spinal
cord after nerve injury in humans.
Implications: Cerebrospinal fluid concentrations of lidocaine after its systemic bolus delivery in
humans indicate that the spinal cord may be the major site of antinociceptive action by this route
of drug
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administration.
40. Perché la lidocaina è efficace nel dolore (acuto
ma + spesso cronico) iperalgesico neuropatico
da lesione nervosa?
Il declino plasmatico dopo un bolo ev della
lidocaina è rapido
Invece
Il livello csf è basso ma persistente nel tempo
La prolungata esposizione del corno post del
midollo spinale alla lido porta alla soppressione
della sensibilizzazione centrale
Azione antinocicettiva
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41. Time course of plasma lidocaine concentrations (A) and
cerebrospinal fluid (CSF) concentrations (B) after the IV
administration of lidocaine 2 mg/kg. The x axis shows the time points at which
samples were taken after lidocaine administration (5-60 min after IV lidocaine). The y axis presents the lidocaine
concentrations as assessed by gas chromatography for plasma (A) and cerebrospinal
fluid (B). All data are presented as measurements of individual samples (open symbols) and their correlating
median values (filled symbols).
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
42. Quindi l’effetto antinocicettivo
della lidocaina
Se effetto analgesico da lidocaina c’è ,esso
dipende dalla concentrazione spinale attiva
sul midollo, corno posteriore ,non a livello
tessutale………
meno si sa degli effetti a livello centrale………
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43. Livelli di lido in cardiologia………..
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44. general anesthesia
can alter the pharmacokinetics of
disparate
drugs through direct effects on drug
elimination mechanisms
and/or indirect effects on hemodynamics.
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
45. Livelli plasmatici di lidocaina
e
anestesia generale
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46. E’ noto che la AG modifica la
distribuzione del flusso ematico ,la
emodinamica generale e distrettuale
Mather LE, Runciman WB, Ilsley AH. Anesthesia-induced changes in regional blood flow.
Implications for drug disposition.Reg Anesth 1982;7(suppl):S23–S33
Runciman WB, Myburgh J, Upton RN, Mather LE. Effects of anaesthesia on drug disposition. In:
Feldman SA, Scurr CF, Paton W, eds. Mechanisms of action of drugs in anaesthetic practice.
2nd ed. London: Edward Arnold, 1993:83–128
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47. Mather LE, Runciman WB, Ilsley AH. Anesthesiainduced changes in regional blood flow. Implications
for drug disposition.Reg Anesth 1982;7(suppl):S23–
S33
Runciman WB, Myburgh J, Upton RN, Mather LE.
Effects of anaesthesia on drug disposition. In:
Feldman SA, Scurr CF, Paton W, eds. Mechanisms of
action of drugs in anaesthetic practice. 2nd ed.
London: Edward Arnold, 1993:83–128
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48. Copeland , SE , Ladd LA, Gu, XO,
Mather LE.The Effects of General Anesthesia on Whole
Body and Regional Pharmacokinetics of Local Anesthetics
at Toxic Doses.Anesth Analg 2008;106:1440 –9
Study of influence of GA on the pharmacokinetics of six local anesthetics administered
IV at approximately the highest recommended doses.
Chronically instrumented ewes (approximately 45–50 kg, n 18)
infused over 3 min with (base doses as HCl salts) bupivacaine (100 mg),
levobupivacaine (125 mg), ropivacaine (150 mg), lidocaine (350 mg), mepivacaine
(350 mg), or prilocaine (350 mg)
on separate occasions when conscious and halothane anesthetized.
Serial arterial, heart, and brain venous blood drug concentrations were measured by
achiral/chiral high-performance liquid chromatography, as relevant.
Whole body pharmacokinetics were assessed by noncompartmental analysis; heart
and brain pharmacokinetics were assessed by mass balance.
Drug blood binding, in the absence and presence of halothane, was assessed by
equilibrium dialysis in vitro.
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
49. Copeland , SE , Ladd LA, Gu, XO,
Mather LE.The Effects of General Anesthesia on Whole
Body and Regional Pharmacokinetics of Local Anesthetics at
Toxic Doses.Anesth Analg 2008;106:1440 –9
RESULTS: Blood local anesthetic concentrations were doubled with
anesthesia because of decreased whole body distribution and clearance
(respectively, to 33% and 52% of values when conscious). Heart and
brain net drug uptake were greater under anesthesia, reflecting slower
efflux from both regions. Clearances of R-bupivacaine S-bupivacaine
and R-prilocaine S-prilocaine, but, mepivacaine clearance was not
enantioselective. Halothane did not influence blood binding of the local
anesthetics.CONCLUSIONS: General anesthesia significantly changed
whole body and regional pharmacokinetics of each local anesthetic as
well as the systemic effects. General anesthesia is thus an important but
frequently overlooked factor in studies of local anesthetic toxicity.
50. Copeland , SE , Ladd LA, Gu, XO,
Mather LE.The Effects of General Anesthesia on Whole Body and
Regional Pharmacokinetics of Local Anesthetics at Toxic
Doses.Anesth
Analg 2008;106:1440 –9
Doses (as base) of :
100 mg bupivacaine,
125 mg levobupivacaine,
150 mg ropivacaine,
350 mg lidocaine,
350 mg mepivacaine,
350 mg prilocaine
as HCl salts) were diluted to 30 mL with 0.9% saline,
and infused into a central venous catheter over 3 min
51. Copeland , SE , Ladd LA, Gu, XO,
Mather LE.The Effects of General Anesthesia on Whole Body and
Regional Pharmacokinetics of Local Anesthetics at Toxic
Doses.Anesth
Analg 2008;106:1440 –9
produced CNS excitotoxicity accompanied by acute
CVS stimulation in all conscious sheep; no overt
effects were observed in anesthetized sheep, but
general anesthesia caused CVS depression, which
was exacerbated by all local anesthetics.
Fatalities occurred with bupivacaine (n 3),
levobupivacaine (n 2),ropivacaine (n 2), and
prilocaine (n 1), all in conscious sheep.
52. Arterial blood levels of LA always greater under
anesthesia Copeland , SE , Ladd LA, Gu, XO,
Mather LE.The Effects of General Anesthesia on Whole Body and Regional Pharmacokinetics
of Local Anesthetics at Toxic Doses.Anesth Analg 2008;106:1440 –9
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53. Pharmacokinetics of LA in adult sheep ,consious or under GA
Copeland , SE , Ladd LA, Gu, XO,
Mather LE.The Effects of General Anesthesia on Whole Body and Regional Pharmacokinetics of
Local Anesthetics at Toxic Doses.Anesth Analg 2008;106:1440
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
–
54. Pharmacokinetics of LA in adult sheep ,consious or under GA
Copeland , SE , Ladd LA, Gu, XO,
Mather LE.The Effects of General Anesthesia on Whole Body and Regional Pharmacokinetics
of Local Anesthetics at Toxic Doses.Anesth Analg 2008;106:1440
Cmax
Tmax
CL
Vss
T1/2
MRT
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
55. Copeland , SE , Ladd LA, Gu, XO,
Mather LE.The Effects of General Anesthesia on Whole Body and
Regional Pharmacokinetics of Local Anesthetics at Toxic
Doses.Anesth
Analg 2008;106:1440 –
Anesthesia approximately doubled the blood
concentrations of all local anesthetics compared with
the respective values while conscious (Figs. 1 and 2).
Anesthesia affected the pharmacokinetic variables of
all six drugs by decreasing their distribution and
clearance, but with relatively minor differences
between drugs (Tables 1 and 2).
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
56. Copeland , SE , Ladd LA, Gu, XO,
Mather LE.The Effects of General Anesthesia on Whole Body and
Regional Pharmacokinetics of Local Anesthetics at Toxic
Doses.Anesth
Analg 2008;106:1440 –
In this study, we found that general anesthesia doubled the drug blood
concentrations of all six local
anesthetics, when compared with the conscious state, by increasing
Cmax/unit dose (an indirect measure of distributional clearance),
decreasing Vss (a direct measure of peripheral uptake), and decreasing
CL (a direct measure of hepatic elimination). Anesthesia also decreased
MRT and T[1/2] (by decreasing Vss more than CL), and Tmax was a
little earlier in conscious animals (an indirect consequence of the CNS
excitotoxicity). At the same time, the toxic response was altered: despite
undergoing much greater CVS depression, all anesthetized animals
survived doses that were lethal in someconscious sheep.5 Thus, drug
blood concentration– response relationships were distorted by inclusion
of general anesthesia in the model.
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
57. Buona biblio sugli AL e loro tox
Copeland , SE , Ladd LA, Gu, XO,
Mather LE.The Effects of General
Anesthesia on Whole Body and
Regional Pharmacokinetics of Local
Anesthetics at Toxic Doses.Anesth
Analg 2008;106:1440 –
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
58. Copeland SE, Ladd LA, Gu X-Q, Mather LE. Effects of general
anesthesia on the central nervous system and cardiovascular
system toxicity of local anesthetics. Anesth Analg
2008;106:1429–39
*Behavioral, cardiovascular, and pharmacokinetic responses
previously instrumented ewes (approximately 45–50 kg, n 18),
on separate occasions when conscious and anesthetized8halothane
/O2)
bupivacaine (100 mg),levobupivacaine (125 mg), ropivacaine (150 mg),
lidocaine (350 mg), mepivacaine (350 mg), prilocaine (350 mg), and
saline (control) infused IV over 3 min.
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
59. Results of toxic doses of LA in
sheep,conscious and anesthetized
LA caused convulsions in conscious sheep, but no overt CNS
effects in anesthetized sheep.
Negative inotropy and slight bradycardia without changes in arterial
blood pressure occurred initially in conscious sheep,followed by
positive inotropy, tachycardia, and hypertension at the abrupt onset
of CNS excitotoxicity, along with widening of QRS complexes.
Fatal cardiac arrhythmias occurred in, respectively, 3 of 11, 2 of 12,
and 2 of 13 conscious sheep infused with bupivacaine,
levobupivacaine, and ropivacaine; in 1 of 9 with prilocaine,
electromechanical dissociation (followed by polymorphic ventricular
tachycardia) caused death.
In anesthetized sheep, cardiovascular depression, preexisting from
the Servizio di Anestesia e Rianimazione Ospedale di exacerbated by all local anesthetics,
general anesthesia, was Faenza(RA)
60. CONCLUSIONS: General anesthesia produced
physiological perturbations, exacerbated local
anesthetic-induced cardiovascular depression, and
changed the pharmacokineticsof toxic doses of local
anesthetics. However, cardiovascular fatalities from
local anesthetics occurred only in conscious
animals.
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
61. The dominant effect of
all local anesthetics was overt CNS excitotoxicity
in all
conscious sheep. There were eight fatalities, all in
conscious
animals and this was a significant finding (Table
1) (conscious versus anesthetized: proportion test
Zcorr
2.54, P 0.011; Fisher’s exact test P 0.0061).
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
62. Left ventricular dp/dt in consciuos or anesthetized
sheep before and after a toxic dose of LA
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
63. Lidocaine toxic dose in a
conscious sheep,non lethal
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
68. When conscious, initial myocardial
depression (decreasing LV-dP/dtmax)
was quickly reversed
with the onset of CNS excitotoxicity. The
longer acting local anesthetics usually
produced a
transient, irregular bradycardia,
premature contractions,
then episodes of tachycardia, including
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
69. The maximal effects generally occurred
at or near
the time of completion of local
anesthetic infusion but,
in conscious sheep, were influenced by
the time at
which CNS excitotoxicity began. The
preexisting myocardial
depression from halothane anesthesia
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
70. SED10 and SED30 were correlated, and
only SED10 is
shown for brevity. The effects shown in
Figures 5 and 6,
except for Emax for QRS width, differed
between conscious
and anesthetized conditions (all
P0.001); in anesthetized
sheep, increases in QRS width lasted
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
77. Contr Bupi Levo Ropi Lido Mepi Prilo
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
78. recovery began 30-min after
drug infusion.
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
79. In conscious sheep, initial CVS
depression was followed
by CVS stimulation and QRS widening,
with similar maximal
effects for all local anesthetics,
apparently reflecting
the causative CNS excitotoxicity. The
ameliorating effect
of anesthesia on CNS toxicity was
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
80. However, other experimental models
have shown that although general
anesthesia suppresses
convulsions and arrhythmias, it does not
necessarily
promote survival, apparently depending
upon the drug
and the model.24,25 This demonstration
of biphasic CVS
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
81. The first sign of serious local anesthetic-induced
toxicity
in conscious subjects is often generalized CNS
excitotoxicity, with or without CVS signs, but
prodromal
signs may be apparent5–7,35 depending mainly
on diligent
observation and the rate of local anesthetic
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
82. might not be detected by usual
clinical monitoring; a rapidly acting
anesthetic for treatment
of CNS toxicity would exacerbate the
CVS depression.
The CNS response to local anesthetics
has been
implicated in their CVS toxicity,13–
15,36,37 but its role
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
83. Halothane causes profound myocardial
depression,
and may predispose the heart to
arrhythmias19–21,38;
however, isoflurane and sevoflurane can
suppress multiform
QRS waves resulting from
bupivacaine.24 Thus, it
could reasonably be argued that the
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
84. In this study, the blood gas
changes in conscious sheep were
consistent with a clear
airway and good oxygenation; CABF
was also maintained,
and thus it is unlikely that cardiac
ischemia or
hypoxemia contributed significantly to
the cardiac dysrhythmias
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
85. In summary, we found that local
anesthetic toxicity in
halothane-anesthetized sheep was very
different from
that in conscious sheep (Table 2). In the
latter, CNS
excitotoxicity stimulated the CVS with
malignant, sometimes
fatal, cardiac arrhythmias. In the former,
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
87. drug/control infusion until 30
min after infusion
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
88. Address correspondence to Emeritus
Professor Laurence E.
Mather, Department of Anaesthesia and
Pain Management, University
of Sydney at Royal North Shore
Hospital, Sydney NSW 2065,
Australia. Address e-mail to
lmather@med.usyd.edu.au.
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
89. Letter to Mather
Dear prof Mather,I have read with the
greatest interest your two companion
articles on toxicity of local
anesthetics*(Copeland , SE , Ladd LA,
Gu, XO, Mather LE.The Effects of
General Anesthesia on Whole Body
and Regional Pharmacokinetics of
Local Anesthetics at Toxic
Doses.Anesth Analg
Servizio
2008;106:1440
di Anestesia e Rianimazione Ospedale di Faenza(RA)
90. Rosenberg PH, Veering BT, Urmey WF. Maximum
recommended doses of local anesthetics: a multifactorial
concept. Reg Anesth Pain Med 2004;29:564–75
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
92. Hemodynamic Physiology and
Thermoregulation in Liposuction
Plast. Reconstr. Surg. 114: 503, 2004
operatively
and associated with diminished sodium,
albumin, urea, and total protein concentrations.
44,45 The ultimate effect of hemodilution
and lower blood viscosity is increased
flow. Decreased peripheral vascular resistance
and vasodilatation (increased arterial radius)
were demonstrated in our patients. This relationship
is described by Poiseuille’s equation.46
Ultimately a greater volume of blood is ejected
from the left ventricle per beat.
93. Propofol Sedation Produces Dose-Dependent Suppression of
Lidocaine-Induced Seizures in Rats
Victor C. Lee, MD, Jeffrey C. Moscicki, MS, and Cosmo A.
DiFazio, MD, PhD
The association of propofol with excitatory motor activity, such as
myoclonic jerking and opisthotonus, in humansand in animals
suggests that it may aggravate clinical seizure activity in some
circumstances, although evidence suggests that under other
circumstances,propofol inhibits seizure activity. In the currentstudy, we
assessed the effect of sedating doses of propofol on lidocaineinduced seizure activity in spontaneously breathing rats receiving no
other anesthetics.Adult Sprague-awley male rats, 300-400 g, were
divided into a control group and three experimental groups
representing three graded levels of propofol sedation.The control rats
then received a lidocaine infusion
at the rate of 150 mg * kg-’ . h-i, resulting in a
Servizio di Anestesia e Rianimazione Ospedale in systemic lidocaine concentrations.
slow, progressive increase di Faenza(RA)
94. Effetto protettivo della
sedazione propofolica
Aumenta la dose ev di lidocaina
necessaria per ottenere le convulsioni
Parallelamente aumenta il livello
plasmatico al quale avvengono le
convulsioni: da 16 a 20,25 microgr/ml
Al dosaggio più elevato evita la comparsa
delle convulsioni
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
95. Continuous propofol sedation
in spontaneously breathing rats receiving no
other anesthetics exerts a protective effect against
lidocaine-induced seizures
. Continuous propofol sedation increased the
seizure dose of lidocaine from 37.7 ? 3.5 mg/kg
(mean 5 SEM) to 52.5 2 2.6 mg/kg (Dose 1, P <
0.05) and 67.9 2 8.6 mg/kg (Dose 2, P < 0.05), and
completely abolished lidocaine seizures at Dose 3.
The lethal dose of lidocaine, 89.4 10.5 mg/kgcontrol
versus 108.7 ? 10.3 mg/kg (Dose l), 98.3 5 10.1
mg/kg (Dose 2), and 93.5 ? 10.4 mg/kg (Dose 3) did
not differ among groups.
The lidocaine levels at seizure threshold were
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
97. Concentrazioni plasmatiche osservate e predette dopo
somministrazione peridurale ripetute di lidocaina da Tucker GT et
al.Observed and predicted accumulation of local anesthetic agents dsuring continuous extradural
analgesia.Br.J.Anaesth. 1977;49:237.
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
98. The tumescent technique: the effect of high tissue pressure and dilute
epinephrine on absorption of lidocaine.
Rubin JP, Bierman C, Rosow CE, Arthur GR, Chang Y, Courtiss EH, May
JW Jr.
The purpose of this work was to determine the effect of tissue pressure during tumescent
injection and presence of low concentration epinephrine on the absorption of lidocaine from
subcutaneous tissues in human volunteers.
Twenty healthy female human volunteers were randomized into four study groups. After body fat
measurements, all subjects received an injection of 7 mg/kg of lidocaine into the subcutaneous
tissues of both lateral thighs. The injected solution consisted of 0.1% lidocaine and 12.5 meq/liter
sodium bicarbonate in normal saline with or without 1:1,000,000 epinephrine. Tissue pressure
was recorded during injection using a specially designed double-barreled needle. The time
required for injection was also recorded. Subjects in group 1 received lidocaine with epinephrine
injected by a high-pressure technique. Group 2 subjects received lidocaine with epinephrine
injected by a low-pressure technique. Group 3 subjects received lidocaine without epinephrine
injected under high pressure. Group 4 subjects received lidocaine without epinephrine injected
under low pressure. Following injection, sequential blood samples were drawn over a 14-hour
period, and plasma lidocaine concentrations were determined by gas chromatography. No
suction lipectomy was performed.
Maximum tissue pressure during injection was 339 ± 63 mmHg and 27 ± 9 mmHg using highand low-pressure techniques, respectively. Addition of 1:1,000,000 epinephrine, regardless of the
pressure of injected fluid, significantly delayed the time to peak plasma concentration by over 7
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
hours. There was no significant difference in the peak plasma concentration of lidocaine among
99. Rygnestad, T, Samdal F.Plasma Concentrations of
Monoethylglycinexylidide during and after Breast
Augmentation.Plast reconstruct Surg 2000;106:728-31
MEGX is pharmacologically active,and its potential for adverse effects has been confirmed in
man.13 In the present study, we found that the maximal plasma concentration of MEGX
occurred as late as 8 to 12 hours after the end of the injection. In three patients, the
concentration was still increasing after 12 hours.
The maximal concentration of MEGX+lidocaine occurred 5 to 12 hours after the end of the
injection.
The magnitude of the MEGX peak suggests that MEGX will contribute to the risk of developing
toxicity when high doses of lidocaine are used.
Lidocaine is present in plasma both in a protein bound pharmacologic inactive fraction and as a
free active fraction. MEGX is probably not protein bound 10 and, thus, only exists in the free and
pharmacologically active form. This finding further underlines the pharmacologic significance of MEGX with
regard to potential lidocaine toxicity. It should also be noted that after an intravenous bolus injection, the
clearance of lidocaine is reduced in the presence of MEGX.13
In previous studies, we have found a significant variation in peak plasma concentrations of lidocaine
in patients undergoing liposuction14 as well as in patients undergoing breast surgery.4 Moreover,
we have reported that it is difficult to assess the risk of lidocaine toxicity without taking into
consideration di Anestesia e Rianimazione Ospedale di Faenza(RA) and the free fraction of the drug.4 In the
Servizio the binding to a1-acid glycoprotein (AAG)
100. Rygnestad, T, Samdal F.Plasma Concentrations of
Monoethylglycinexylidide during and after Breast Augmentation.Plast
reconstruct Surg 2000;106:728-31
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
101. Kenkel JM,Lipschitz , A H,Shepherd G,Armstrong VW,Streit
F,Oellerich M, Luby M, Rohrich R,Brown SA.D.Pharmacokinetics and
Safety of Lidocaine and Monoethylglycinexylidide in Liposuction: A
Microdialysis Study.J Plast Surg . 114,2004, 516-524
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
102. Kenkel JM,Lipschitz , A H,Shepherd G,Armstrong VW,Streit
F,Oellerich M, Luby M, Rohrich R,Brown SA.D.Pharmacokinetics and
Safety of Lidocaine and Monoethylglycinexylidide in Liposuction: A
Microdialysis Study.J Plast Surg . 114,2004, 516-524
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
103. More information would be desirable on the factors controlling the
resorption of lidocaineduring liposuction therapy to improve durationof
effect. Perry et al.43 studied postoperativepain at 5, 30, 60, and 120
minutes and on the first postoperative day after liposuction and found
that there was no statistically significant
difference between paired, mirrored sides of 10 subjects when
lidocaine was used on only one side. The study concluded that
lidocaine is not necessary in liposuction. Further research into
diminishing the dose of lidocaine in wetting solution is warranted, as
the safety profile of liposuction may be significantly improved by
eliminating lidocaine toxicity as a potential complication. Lidocaine’s
impact on diminishing intraoperative general anesthesia deserves
further exploration.
104. Rygnestad T, Brevik B, Samdal F.
Plasma Concentrations of Lidocaine and
[alpha]1-Acid Glycoprotein during and
after Breast Augmentation.Plast
Reconstruct Surg., 1999;109:12671272
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
105. The mean lidocaine dose was 18.2 mg/kg (range 16.3 to 21.9
mg/kg). The mean injection time was 23.3 minutes (range, 16
to 35 minutes). Rygnestad T, Brevik B, Samdal F. Plasma Concentrations of Lidocaine and
[alpha]1-Acid Glycoprotein during and after Breast Augmentation.Plast Reconstruct Surg., 1999;109:12671272
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
106. Rygnestad T, Brevik B, Samdal F. Plasma Concentrations of
Lidocaine and [alpha]1-Acid Glycoprotein during and after
Breast Augmentation.Plast Reconstruct Surg., 1999;109:12671272
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
107. Rygnestad T, Brevik B, Samdal F. Plasma Concentrations of
Lidocaine and [alpha]1-Acid Glycoprotein during and after
Breast Augmentation.Plast Reconstruct Surg., 1999;109:12671272
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
108. 0 pioid-insensitive neuropathic pain due to nerve injury is one of the
most difficult problems in pain management. Therapeutic approaches
for these painful sensations, which can be evoked by thermal or
mechanical stimuli, include the use of sodium channel blockers such
as carbamazepine, tocainide,
phenytoin, mexiletine, or lidocaine (1,2). Lidocaine and mexiletine
alleviate consistent neuropathic pain states (3-5). Local anesthetics
act in both the peripheral and the central nervous systems (6-9). At the
peripheral level, local anesthetics inhibit neuronal transduction,
decrease the release of inflammatory mediators, inhibit migration of
leukocytes, and suppress albumin extravasation (10). At the central
site,local anesthetics block neuronal activity at the spinal
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
109. Effetti periferici degli anestetici locali
Inibizione della trasduzione neuronale
Riduzione dei mediatori nfiammatori
Inibizione della migrazione leucocitaria
Soppressione dello stravaso albuminico
Inibizione della generazione di impulsi a
livello del nervo leso,neuromi inclusi
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
110. Effetti centrali degli anestetici locali
Riduzione della scarica a partenza dal
ganglio della radice dorsale
Blocco della attività neurale spinale a
livello del corno post.
Modulazione della liberazione di
neurotrasmettitori
Soppressione della attività delle fibre C
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
111. dorsal horn level, thus modulating the release of excitatory
neurotransmitters (6,ll). However, the underlying mechanisms for the
analgesic action of systemically administered lidocaine remain
controversial.
Some preclinical studies provide evidence for a predominant
inhibition of impulse generation arising from injured nerve segments
or any associated dorsal root ganglion (12,13). Devor et al. (14)
found a selective blocking effect for systemically delivered lidocaine
by inhibiting ectopic discharges from experimental neuromas without
affecting axonal conduction.
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
112. However, several investigators propose a predominant central site of
action for the use of systemic lidocaine or other sodium channel
blockers (3,6,15).
Sotgiu et al. (16) found that systemically administered lidocaine
preferentially acts on the hyperactive, wide dynamic-range neurons
found in the dorsal horn, resulting in analgesia. This type of sensitized
neuron is often found in hyperalgesic pain states. Further important
evidence regarding a central site of action was demonstrated by the
spinal suppression of C-fiberevoked activity seen with low
concentrations after systemic lidocaine (17).
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
113. Hyperalgesic pain states occur after surgery, trauma,and metabolic
disorders, and they are also related to sympathetically maintained pain
syndromes (3). As a result of continuous C-fiber stimulation,
hyperalgesia represents a state of facilitated sensory processing at the
level of the spinal dorsal horn (3,12). As a clinical symptom of nerve
injury, hyperalgesic pain often leads to protective immobilization, which
may result in malformation or loss of function in the affected body
region. Preclinical and clinical studies have shown that sodium channel
blockers such as lido- Caine, given systemically or spinally, effectively
inhibit this pain (18-20). This analgesic effect can be achieved with small
doses of lidocaine, which do not alter acute nociceptive pain thresholds
or axonal conduction.
This was reported by Wallace et al. (21), who revealed no prominent
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
effects by systemic lidocaine infusions on acute heat, cold, or
114. Their findings are in accordance with those ofBach et al. (22), who showed that IV
lidocaine decreases neuropathic pain without affecting the neurosensory system. The
administration of a bolus dose of 2 mg/kg IV lidocaine produced plasma
concentrations of lidocaine similar to those for which Wallace et al. (17) demonstrated
a decrease in pain scores and a concomitant reduction in the size of the receptive field
to which the pain was referred. The onset of the inhibition of spinal dorsal horn neuron
activity after IV lidocaine occurs within 5-7 min, as shown in a preclinical model. The
antihyperalgesic action of systemic lidocaine is mainly attributed to the spinal cord.
Lido- Caine has a plasma half-life of approximately 90 min after bolus injection, an
octanol to water distribution coefficient of 110 at 36”C, and pH 7.4; it rapidly accesses
the central nervous system after systemic delivery (l&23). At the spinal cord,
systemically applied lidocaine blocks the release of substance I’ (24), inhibits the
discharge of wide dynamic neurons (25), and suppresses the discharge induced by
the release of the excitatory amino acid glutamate (7). Previous studies of IV bolus
delivery of lidocaine recorded inconsistent plasma levels (26,27
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
115. ). This finding is supported by our
observation of a very fast decay in
plasma lidocaine
concentrations and an interindividual
difference for
the plasma peak obtained after IV
lidocaine injection.
As demonstrated in our present study,
there was no
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)