We reviewed the cases of 91 consecutive patients with disabilities who required general anesthesia at a tertiary referral center for dental treatment with a view to determining the factors that create difficulties in the anesthetic management. The more important of these are the special difficulties involved in making preoperative assessments of these patients and the difficulty in establishing monitoring. Other difficulties in anesthesia for these patients involve problems with gaining intravenous access, problems in determining when there has been adequate recovery from anesthesia, and problems in determining the degree of discomfort or pain the patients experience after dental treatment. Another potential hazard in this group of patients is the risk of drug interactions. We emphasize the need to train anesthetists in the care of disabled patients.
This paper addresses the problem of estimating the depth of anesthesia in clinical practice where many drugs are used in combination. The aim of the project is to use pharmacokinetically-derived data to predict episodes of light anesthesia. The weighted linear combination of anesthetic drug concentrations was computed using a stochastic pharmacokinetic model. The clinical definition of light anesthesia was based on the hemodynamic consequences of autonomic nervous system responses to surgical stimuli. A rule-based expert system was used to review anesthesia records to determine instances of light anesthesia using hemodynamic criteria. It was assumed that light anesthesia was a direct consequence of the weighted linear combination of drug concentrations in the patient's body that decreased below a certain threshold. We augmented traditional two-compartment models with a stochastic component of anesthetics' concentrations to compensate for interpatient pharmacokinetic and pharmacodynamic variability. A cohort of 532 clinical anesthesia cases was examined and parameters of two compartment pharmacokinetic models for 6 intravenously administered anesthetic drugs (fentanyl, thiopenthal, morphine, propofol, midazolam, ketamine) were estimated, as well as the parameters for 2 inhalational anesthetics (N2O and isoflurane). These parameters were then prospectively applied to 22 cases that were not used for parameter estimation, and the predictive ability of the pharmacokinetic model was determined. The goal of the study is the development of a pharmacokinetic model that will be useful in predicting light anesthesia in the clinically relevant circumstance where many drugs are used concurrently.
Anesthesia drugs have impact on multiple outcomes of an anesthesia patient. Most typical outcomes include anesthesia depth, blood pressures, heart rates, etc. Traditional diagnosis and control in anesthesia focus on a one-drug-one-outcome scenario. This paper studies the problem of real-time modeling for monitoring, diagnosing, and predicting multiple outcomes of anesthesia patients. It is shown that consideration of multiple outcomes is necessary and beneficial for anesthesia managements. Due to limited real-time data, real-time modeling in multi-outcome modeling requires low-complexity model strucrtures. This paper introduces a method of decision-oriented modeling that significantly reduces the complexity of the problem. The method employs simplified and combined model functions in a Wiener structure to contain model complexity. The ideas of drug impact prediction and reachable sets are introduced for utility of the models in diagnosis, outcome prediction, and decision assistance. Clinical data are used to evaluate the effectiveness of the method.
Modeling; anesthesia; multi-outcome; diagnosis; prediction; control.
Placing a patient in a state of general anesthesia is crucial for safely and humanely performing most surgical and many nonsurgical procedures. How anesthetic drugs create the state of general anesthesia is considered a major mystery of modern medicine. Unconsciousness, induced by altered arousal and/or cognition, is perhaps the most fascinating behavioral state of general anesthesia. We perform a systems neuroscience analysis of the altered arousal states induced by five classes of intravenous anesthetics by relating their behavioral and physiological features to the molecular targets and neural circuits at which these drugs are purported to act. The altered states of arousal are sedation-unconsciousness, sedation-analgesia, dissociative anesthesia, pharmaco-logic non-REM sleep, and neuroleptic anesthesia. Each altered arousal state results from the anesthetic drugs acting at multiple targets in the central nervous system. Our analysis shows that general anesthesia is less mysterious than currently believed.
dexmedetomidine; droperidol; ketamine; opioids; propofol
Na channels are the source of excitatory currents for the nervous system and muscle. They are the target for a class of drugs called local anesthetics (LA), which have been used for local and regional anesthesia and for excitatory problems such as epilepsy and cardiac arrhythmia. These drugs are prototypes for new analgesic drugs. The drug-binding site has been localized to the inner pore of the channel, where drugs interact mainly with a phenylalanine in domain IV S6. Drug affinity is both voltage- and use-dependent. Voltage-dependency is the result of changes in the conformation of the inner pore during channel activation and opening, allowing high energy interaction of drugs with the phenylalanine. LA drugs also reduce the gating current of Na channels, which represents the movement of charged residues in the voltage sensors. Specifically, drug binding to phenylalanine locks the domain III S4 in its outward (activated) position, and slows recovery of the domain IV S4. Although strongly affecting gating, LA drugs almost certainly also block by steric occlusion of the pore. Molecular definition of the binding and blocking interactions may help in new drug development.
lidocaine; molecular modeling; Na channel; local anesthetics; gating currents
General anesthetics are used during medical and surgical procedures to reversibly induce a state of total unconsciousness in patients. Here, we investigate, from a dynamic network perspective, how the cortical and cardiovascular systems behave during anesthesia by applying nonparametric spectral techniques to cortical electroencephalography, electrocardiogram and respiratory signals recorded from anesthetized rats under two drugs, ketamine-xylazine (KX) and pentobarbital (PB). We find that the patterns of low-frequency cortico-cardio-respiratory network interactions may undergo significant changes in network activity strengths and in number of network links at different depths of anesthesia dependent upon anesthetics used.
We describe the anesthetic management and implications of two patients with anti-N-methyl-D-aspartate (NMDA) receptor encephalitis. Anti-NMDA receptor encephalitis is a neurological disorder caused by production of antibodies to the NMDA receptor. The NMDA receptor is the target of many drugs used in anesthesia. It is important to understand the pharmacologic interactions these anesthetics have with a disabled NMDA receptor while preparing an anesthetic plan for patients with anti-NMDA receptor encephalitis. Symptoms of the disease such as psychosis, paroxysmal sympathetic hyperactivity, and central hypoventilation pose risks to the induction and maintenance of anesthesia in these patients.
Anesthesia methods and drugs affect postoperative nausea and vomiting. Propofol is known to have antiemetic effects. We compared the incidence of postoperative vomiting (POV) in children undergoing an adenotonsillectomy; anesthesia in one group was induced with propofol and maintained with sevoflurane and nitrous oxide, and the other group received total intravenous anesthesia (TIVA) with propofol-remifentanil.
Ninety children, ASA physical status I, were assigned randomly to one of two groups. In the PSN group, anesthesia was maintained with 2-3 vol% sevoflurane and 50% nitrous oxide. In the PR group, anesthesia was maintained with 10 mg/kg/h propofol and 0.25 µg/kg/min remifentanil. In both groups, anesthesia was induced with 0.5 µg/kg remifentanil and 2 mg/kg propofol. The incidence of POV and the need for rescue antiemetics were assessed in the postanesthesia care unit at 6, 12, and 24 hours postoperatively.
The total incidence of POV was not significantly different between the groups; POV occurred in eight (17.7%) and three (6.7%) children in the PSN and PR groups, respectively. Postoperative frequency of retching in the recovery room was significantly higher in the PSN group, with four children (8.9%) in the PSN group compared to none (0%) in the PR group (P = 0.041). The frequency of POV 24 hrs after exiting the recovery room tended to be higher in the PSN group than the PR group, but no statistically significant difference was observed.
If the development of POV in the early anesthetic recovery phase of children undergoing adenotonsillectomy is adequately prevented, propofol-induced anesthesia maintained with sevoflurane-nitrous oxide is as safe as TIVA with propofol-remifentanil.
Adenotonsillectomy; Pediatric; PONV; Sevoflurane; TIVA
A healthy but slightly pale 24-year-old female patient with a history of "turning blue" following dental procedures performed under local anesthesia claimed allergies to sulfa drugs, aspirin, Benadryl, and "all caines." The patient also acknowledged mild cyanosis after extreme exertion, Native American ancestry, and a 1996 diagnosis of methemoglobinemia following administration of a sulfa drug. Previous medical and dental records were reviewed. Restoration of several teeth and extraction of 2 third-molar teeth were completed under general anesthesia. Anesthesia was induced with propofol, nasotracheal intubation was accomplished with succinylcholine, and anesthesia was maintained with desflurane in oxygen supplemented by meperidine without local anesthesia. Vital signs, including pulse oximetry, remained stable, and the patient was dismissed after a 2-hour recovery/observation period. The patient experienced no postoperative complications. This case report provides a review of literature and clinical guidelines for management of methemoglobinemia-susceptible patients.
Asthmatic patients who undergo outpatient anesthesia are typically prescribed one or more drugs for treatment. Some of these agents have narrow therapeutic ranges and are associated with potentially serious adverse reactions, toxic effects, or drug interactions. Various clinical signs of toxicity may be first uncovered during routine monitoring of an office anesthetic. The case reported here demonstrates the need for proper understanding of the asthmatic patient's medical history and an appreciation for the medications used to control the disease. A sudden cardiovascular event possibly related to drug toxicity is witnessed and treated in an asthmatic patient during intravenous sedation. A possible drug interaction with a non-asthmatic medication taken concomitantly by the patient is implicated and discussed. In addition to the case report, the broad classification of drugs employed for bronchial asthma and their effects is reviewed.
We aim to compare selective spinal anesthesia and general anesthesia with regard to postoperative recovery and fast‐track eligibility in day surgeries.
MATERIALS AND METHOD:
Sixty geriatric outpatient cases, with ASA II‐III physical status and requiring short‐duration transurethral intervention, were enrolled in the study. The cases were split into 2 groups: as general anesthesia (Group GA) and selective spinal anesthesia (Group SSA). Group GA (n = 30) received propofol 2 mg kg‐1 (until loss of eyelash reflex), remifentanil induction 0.5‐1 µg kg‐1, and laryngeal mask. Maintenance was achieved by 4‐6% desflurane in 60% N2O and 40% O2 along with remifentanil infusion at 0.05 µg /kg‐1 /min‐1. Drugs were discontinued after the withdrawal of the ureteroscope, and extubation was carried out with 100% O2. Group SSA (n = 30) received 0.5% spinal anesthesia via L4‐5 space by 0.5% hyperbaric bupivacaine 5 mg. Anesthesia preparation time, time to surgical anesthesia level, postoperative fast‐tracking, and time to White‐Song recovery score of 12, were noted. In the operating room, we evaluated hemodynamics, nausea/vomiting, surgeon and patient satisfaction with anesthesia, perioperative midazolam‐fentanyl administration, postoperative pain, and discharge time.
Anesthesia preparation time, length of surgery, anesthesia‐related time in the operating room, time to sit, and time to walk were significantly low in Group GA (p<0.05), whereas time to fast‐track eligibility, length of stay in the PACU, discharge time, and other parameters were similar in both of the groups.
While anesthesia preparation time, length of surgery, start time of surgery, time to sit, and time to walk were shorter in the General Anesthesia group, time to fast‐track eligibility, phase 1 recovery time, and discharge time were similar among patients subjected to selective spinal anesthesia.
Selective spinal anesthesia; General anesthesia; Postoperative recovery; Fast‐track; Geriatri
During the administration of anesthesia, the anesthesia provider has historically created a paper record, charted manually, that included extensive patient care–related data (vital signs, other parameters, etc) and commentaries. DocuSys, a proprietary anesthesia information management system (AIMS), creates an electronic version of the anesthesia record and provides additional information. It electronically captures data from clinical monitors and other sources, including scheduling applications and laboratory computers. The AIMS facilitates chart entries such as drug doses and case narratives. Benefits of an AIMS include improved legibility of the anesthesia record and greater efficiency in documentation efforts. Use of the AIMS assists the practitioner with decision support logic, such as the timing of antibiotic administration and the inclusion of legally required documentation. Upon case completion, the AIMS data are immediately available to other information systems, such as billing and medical records. Data can be made available from a single case or, more important, from thousands of cases to analyze variables such as efficiency of services, adherence to best practices, patient outcomes, and clinical research. The AIMS was deployed at the main campus of the Ochsner Health System on March 26, 2009. In this article, we discuss the issues involved in the AIMS implementation process: the successes, surprises, and continued challenges.
Anesthesia; electronic medical record; informatics
Patients have anxiety and fear of complications due to general anesthesia. Through new instruments and local anesthetic drugs, a variety of anesthetic methods have been introduced. These methods keep hospital costs down and save time for patients. In particular, the target-controlled infusion (TCI) system maintains a relatively accurate level of plasma concentration, so the depth of anesthesia can be adjusted more easily. We conducted this study to examine whether intravenous anesthesia using the TCI system with propofol and remifentanil would be an effective method of anesthesia in breast augmentation.
This study recruited 100 patients who underwent breast augmentation surgery from February to August 2011. Intravenous anesthesia was performed with 10 mg/mL propofol and 50 µg/mL remifentanil simultaneously administered using two separate modules of a continuous computer-assisted TCI system. The average target concentration was set at 2 µg/mL and 2 ng/mL for propofol and remifentanil, respectively, and titrated against clinical effect and vital signs. Oxygen saturation, electrocardiography, and respiratory status were continuously measured during surgery. Blood pressure was measured at 5-minute intervals. Information collected includes total duration of surgery, dose of drugs administered during surgery, memory about surgery, and side effects.
Intraoperatively, there was transient hypotension in two cases and hypoxia in three cases. However, there were no serious complications due to anesthesia such as respiratory difficulty, deep vein thrombosis, or malignant hypertension, for which an endotracheal intubation or reversal agent would have been needed. All the patients were discharged on the day of surgery and able to ambulate normally.
Our results indicate that anesthetic methods, where the TCI of propofol and remifentanil is used, might replace general anesthesia with endotracheal intubation in breast augmentation surgery.
Anesthesia, intravenous; Mammaplasty; Propofol; Remifentanil
The ex-utero intrapartum treatment (EXIT) is one type of fetal surgery, performed before delivery while the fetus remains attached to the uteroplacental circulation. This intervention improves neonatal morbidity and mortality of certain congenital diseases. For instance, securing the airway of a fetus with congenital airway obstruction while on uteroplacental circulation prevents the hypoxemia during the establishment of an airway post-delivery. Anesthesia for fetal surgery now incorporates new knowledge of the maternal/fetal response to anesthetic agents. This chapter reviews for the EXIT procedure the effects of maternal anesthesia on fetal hemodynamics, intravenous anesthesia to supplement inhalational anesthesia in order to provide maternal-fetal hemodynamic stability during surgery, intraoperative fetal monitoring, maternal pharmacokinetics approach to study placental drug transfer and fetal pharmacokinetics to improve our understanding of the effects of maternal anesthesia on the fetus.
Psychological disorders and psychiatric diseases have been on the rise since the last three decades. An increasing number of such patients are encountered nowadays for elective or emergency surgery. A multi-array of challenges are faced while anesthetizing these patients or treating them in an intensive care unit. The problems include the deteriorated mental physiology, altered cognition and the possible drug interactions with psychotropic medications. The challenge starts from the preoperative assessment stage. Knowledge of the pharmacological profile of the various anti-psychotic drugs, their side-effects and drug interactions are of prime importance for an anesthesiologist to facilitate smooth delivery of anesthesia in such patients. It is important to formulate a clear plan to deal with any challenge in the perioperative or postoperative period. All the clinical aspects and various definitions of mental disorders in the present article have been used as per the fourth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV). We reviewed the advances in psychiatric diseases, their treatment and their implications on delivery of anesthesia.
Anxiety disorders; bipolar disorder; delirium; dementia; mood disorders; schizophrenia; substance abuse
Background and Aims:
Keeping in consideration the merits of total intravenous anesthesia (TIVA), a genuine attempt was made to find the ideal drug combinations which can be used in general anesthesia. This study was conducted to evaluate and compare two drug combinations of TIVA using propofol–ketamine and propofol–fentanyl and to study the induction, maintenance and recovery characteristics following anesthesia with these techniques.
Settings and Design:
A case control study was conducted, which included 100 patients, in the department of Anaesthesiology and Intensive care, Government Medical College and Hospital, Patiala.
Patients and Methods:
A hundred patients between the ages of 20 and 50 years of either gender were divided into two groups of 50 each, and they underwent elective surgery of approximately 1 h duration. Group I received propofol–ketamine while group II received propofol–fentanyl for induction and maintenance of anesthesia. All the results were tabulated and analyzed statistically with student's unpaired t-test and chi-square test.
Propofol–fentanyl combination produced a significantly greater fall in pulse rate (PR; 9.28% versus 0.23%) and in both systolic (7.94% versus 0.12%) and diastolic blood pressures (BP; 8.10% versus 0.35%) as compared to propofol–ketamine during induction of anesthesia. Propofol–ketamine combination produced stable hemodynamics during maintenance phase while on the other hand propofol–fentanyl was associated with a slight increase in both PR and BP. During recovery, ventilation score was better in group I while movement and wakefulness score was better in group II. Mean time to protrusion of tongue and lifting of head was shorter in group I.
Both propofol–ketamine and propofol–fentanyl combinations produce rapid, pleasant and safe anesthesia with only a few untoward side effects and only minor hemodynamic effects.
Propofol-ketamine; propofol-fentanyl; total intravenous anesthesia
The popularity of day case surgical procedures has increased immensely over the last few years. Though various techniques are available for carrying out day-case anesthesia, preference for a technique depends upon the type of procedure, patient profile, associated co-morbidities, available infrastructure and back-up facilities, monitoring devices and comfort of the attending anesthesiologist with the technique. Day-case spinal anesthesia for ambulatory surgery has gained a wider acceptance and numerous drugs are available for use in loco-regional anesthesia. Articaine is one such amide local anesthetic drug which is increasingly being used in day care surgeries. Properties of articaine such as faster onset, shorter elimination time and rapid recovery from sensory and motor blockade make it a very useful agent in local and regional anesthesia for day care surgical procedures. This article aims to review these properties of articaine so as to evaluate how useful articaine can be for ambulatory surgical procedures.
Articaine; Bupivacaine; Day-care surgery; Lignocaine; Neuraxial anesthesia; Prilocaine; Regional anesthesia
General anesthetic drugs interact with many receptors in the nervous system, but only a handful of these interactions are critical for producing anesthesia. Over the last 20 years, neuropharmacologists have revealed that one of the most important target sites for general anesthetics is the GABAA receptor. In this review we will discuss what is known about anesthetic – GABAA receptor interactions.
GABAA Receptor; General Anesthetic; Isoflurane; Desflurane; Sevoflurane; Propofol; Etomidate; Barbiturates.
Analgesic and anesthetic drugs may have an impact on the results achieved from animal experiments. In the study presented here, we try to enlighten whether anesthesia with fentanyl/fluniasone and midazolam (Hypnorm and Dormicum) has an influence on measurements of hemoglobin in mice. In a cross-over study, we have compared hemoglobin levels in two groups of mice: anesthetized versus non-anesthetized and found significant decrease in hemoglobin levels in the anesthetized group (p < 0.05) unrelated to which group received the anesthesia. The mean hemoglobin levels after intraperitoneal administration of Hypnorm and Dormicum was 8.7 mmol/L compared to mean hemoglobin 9.9 mmol/L before anesthesia (p < 0.001), and the decrease lasted for more than 30 min. These results show that anesthesia can be an important confounder in studies involving measurements of hemoglobin, and this should be taken into account when planning studies and analyzing data.
anesthesia; hemoglobin; in vivo; fentanyl; midazolam
Morphine is the core of perioperative pain management. However, when it comes to cancer surgery the possibility that this drug might affect tumor recurrence and metastasis has raised concerns. The results of two recent retrospective clinical trials indicated that regional anesthesia/analgesia might be beneficial in prostate and breast cancer surgery. It was proposed that morphine could be responsible for the higher recurrence and mortality rate observed in the general anesthesia/opioid analgesia groups. Nevertheless, the results of several other retrospective studies and one randomized prospective trial failed to confirm any advantage for regional anesthesia/analgesia over general anesthesia and opioid analgesia. Moreover laboratory data on the effect of morphine on cancer are contradictory, ranging from tumor-promoting to anti-tumor effects. Considering that surgical stress and pain promote the recurrence and spread of cancer, choosing a proper analgesic strategy is of high significance. Although the question of whether morphine causes any harm to cancer patients remains unanswered, alternative analgesic regimens could be used concomitant to or instead of morphine to limit its potential adverse effects.
morphine; regional; anesthesia; analgesia; cancer; surgery
Purpose of Review
A cooperative patient is essential in maintaining stone targeting for optimal fragmentation during extracorporeal shock wave lithotripsy (ESWL). Therefore, it is important to choose an appropriate analgesic with minimal adverse effects. The guidelines for pain management during ESWL have not been established.
Various analgesic agents including opioids (morphine, pethidine, and fentanyl), nonsteroidal anti-inflammatory drugs (NSAIDS - diclofenac, propofol, ketorolac, and piroxicam), local anesthetic agents and a number of combinations have been used during ESWL by various techniques (general anesthesia, regional anesthesia, subcutaneous and intravenous injections, patient-controlled analgesia, and monitored anesthesia care). Cutaneous creams like eutectic mixture of local anesthesia (EMLA) whether used alone or in combination with oral NSAIDS have also been used and are able to reduce analgesic requirements. Topical application of a combination of dimethyl sulfoxide and lidocaine has also been found to be effective.
The ideal analgesic, offering optimal pain control, minimal side effects, and cost-effectiveness is still elusive. Opioids administered using various techniques, provide effective analgesia, but require active monitoring of patient for potential adverse effects. Combination therapy (oral NSAID and occlusive dressing of EMLA, DMSO with lidocaine) offers an effective alternative mode for achieving analgesia with minimal morbidity. This therapy avoids the need for general anesthesia, injectable analgesics, and opioids along with their side effects.
Analgesia; ESWL; urolithiasis
Propofol has been shown in clinical studies to be a safe, effective, hypnotic, and amnesic anesthetic agent at induction doses of 2-2.5 mg/kg and maintenance doses of approximately 9mg/kg per hour. Significant post-induction hypotension reported earlier can be reduced to a all in MAP of less than 25% when the drug is used alone (without nitrous oxide or narcotic premedication). Post-induction apnea is minimized by avoidance of pre-induction hyperventilation. Acute and long term venous tolerance is acceptable. Emergence from anesthesia induced and maintained with propofol is rapid, predictable and relatively free of postoperative complications. Incidence of drug interaction is low. Propofol causes no adrenocortical suppression and is not potentiated by ethanol, diazepam, amitriptyline or phenelzine. Preliminary investigation of propofol as an intravenous sedative agent at subanesthetic doses has been favorable.
General anesthesia is not a uniform state of the brain. Ongoing activity differs between light and deep anesthesia and cortical response properties are modulated in dependence of anesthetic dosage. We investigated how anesthesia level affects cross-modal interactions in primary sensory cortex. To examine this, we continuously measured the effects of visual and auditory stimulation during increasing and decreasing isoflurane level in the mouse visual cortex and the subiculum (from baseline at 0.7 to 2.5 vol % and reverse). Auditory evoked burst activity occurred in visual cortex after a transition during increase of anesthesia level. At the same time, auditory and visual evoked bursts occurred in the subiculum, even though the subiculum was unresponsive to both stimuli previous to the transition. This altered sensory excitability was linked to the presence of burst suppression activity in cortex, and to a regular slow burst suppression rhythm (∼0.2 Hz) in the subiculum. The effect disappeared during return to light anesthesia. The results show that pseudo-heteromodal sensory burst responses can appear in brain structures as an effect of an anesthesia induced state change.
Minimally invasive medical procedures such as biopsies, anesthesia drug injections, and brachytherapy cancer treatments require inserting a needle to a specific target inside soft tissues. This is difficult because needle insertion displaces and deforms the surrounding soft tissues causing the target to move during the procedure. To facilitate physician training and preoperative planning for these procedures, we develop a needle insertion motion planning system based on an interactive simulation of needle insertion in deformable tissues and numerical optimization to reduce placement error. We describe a 2-D physically based, dynamic simulation of needle insertion that uses a finite-element model of deformable soft tissues and models needle cutting and frictional forces along the needle shaft. The simulation offers guarantees on simulation stability for mesh modications and achieves interactive, real-time performance on a standard PC. Using texture mapping, the simulation provides visualization comparable to ultrasound images that the physician would see during the procedure. We use the simulation as a component of a sensorless planning algorithm that uses numerical optimization to compute needle insertion offsets that compensate for tissue deformations. We apply the method to radioactive seed implantation during permanent seed prostate brachytherapy to minimize seed placement error.
Brachytherapy; medical robotics; motion planning; needle insertion; physically based simulation; sensorless planning
The presence of inflammation decreases local anesthetic efficacy, especially in dental anesthesia. Although inflammatory acidosis is most frequently cited as the cause of such clinical phenomena, this has not been experimentally proved. We verified the acidosis mechanism by studying the drug and membrane lipid interaction under acidic conditions together with proposing an alternative hypothesis. Liposomes and nerve cell model membranes consisting of phospholipids and cholesterol were treated at different pH with lidocaine, prilocaine and bupivacaine (0.05%–0.2%, w/v). Their membrane-interactive potencies were compared by the induced-changes in membrane fluidity. Local anesthetics fluidized phosphatidylcholine membranes with the potency being significantly lower at pH 6.4 than at pH 7.4 (p < 0.01), supporting the acidosis theory. However, they greatly fluidized nerve cell model membranes even at pH 6.4 corresponding to inflamed tissues, challenging the conventional mechanism. Local anesthetics acted on phosphatidylserine liposomes, as well as nerve cell model membranes, at pH 6.4 with almost the same potency as that at pH 7.4, but not on phosphatidylcholine, phosphatidylethanolamine and sphingomyelin liposomes. Since the positively charged anesthetic molecules are able to interact with nerve cell membranes by ion-paring with anionic components like phosphatidylserine, tissue acidosis is not essentially responsible for the local anesthetic failure associated with inflammation. The effects of local anesthetics on nerve cell model membranes were inhibited by treating with peroxynitrite (50 μM), suggesting that inflammatory cells producing peroxynitrite may affect local anesthesia.
inflammatory acidosis; local anesthetic failure; membrane lipid interaction; hypothetic mechanism; inflammatory peroxynitrite