Drug interaction is fundamental in performing anesthesia. A response surface model (RSM) is a very useful tool for investigating drug interactions. The methodology appeared many decades ago, but did not receive attention...Drug interaction is fundamental in performing anesthesia. A response surface model (RSM) is a very useful tool for investigating drug interactions. The methodology appeared many decades ago, but did not receive attention in the field of anesthesia until the 1990s. Drug investigations typically start with pharmacokinetics, but it is the effects on the body clinical anesthesiologists really care about. Typically, drug interactions are divided into additive, synergistic, or infra-additive. Traditional isobolographic analysis or concentration-effect curve shifts are limited to a single endpoint. Response surface holds the complete package of isobolograms and concentration effect curves in one equation for a given endpoint, e.g., loss of response to laryngoscopy. As a pharmacodynamic tool, RSM helps anesthesiologists guide their drug therapy by navigating the surface. We reviewed the most commonly used models: (1) the Greco model; (2) Reduced Greco model; (3) Minto model; and (4) the Hierarchy models. Each one has its unique concept and strengths. These models served as groundwork for researchers to modify the formula to fit their drug of interest. RSM usually work with two drugs, but three-drug models can be constructed at the expense of greatly increasing the complexity. A wide range of clinical applications are made possible with the help of pharmacokinetic simulation. Pharmacokinetic-pharmcodynamic modeling using the RSMs gives anesthesiologists the versatility to work with precision and safe drug interactions. Currently, RSMs have been used for predicting patient responses, estimating wake up time, pinpointing the optimal drug concentration, guide therapy with respect to patient's well-being, and aid in procedures that require rapid patient arousal such as awake craniotomy or Stagnara wake-up test. There is no other model that is universally better than the others. Researches are encouraged to find the best fitting model for different occasions with an objective measure.
OBJECTIVE: This randomized, double-blind study was conducted to evaluate the effect of gabapentin pretreatment on the hemodynamic response to laryngoscopy and endotracheal intubation (LETI) in treated hypertensive patien...OBJECTIVE: This randomized, double-blind study was conducted to evaluate the effect of gabapentin pretreatment on the hemodynamic response to laryngoscopy and endotracheal intubation (LETI) in treated hypertensive patients undergoing surgery. METHODS: A total of 100 controlled hypertensive patients aged 35-60 years, undergoing elective surgery under general anesthesia with endotracheal intubation, were randomly allocated into three groups. Group 1 patients received placebo at night and 2 hours prior to induction of anesthesia. Group 2 patients received placebo at night and 800 mg gabapentin 2 hours prior to induction of anesthesia. Group 3 patients received 800 mg gabapentin at night and 2 hours prior to induction of anesthesia. Anesthesia was induced with thiopentone, fentanyl, and vecuronium and maintained with isoflurane in oxygen and nitrous oxide. Patients' heart rate (HR), blood pressure (BP), and electrocardiography (ECG) changes were recorded prior to induction, after induction, and at 0 minutes, 1 minute, 3 minutes, 5 minutes, and 10 minutes after intubation. Any episodes of hypotension, bradycardia, tachycardia, hypertension, arrhythmia, and ST-T wave changes were recorded and treated accordingly. RESULTS: The HR was comparable among groups, with a transient rise just after intubation, followed by a gradual fall thereafter at 3 minutes, 5 minutes, and 10 minutes compared with baseline. A significant increase in BP after intubation was reported in Group 1 but not in Group 2 and Group 3. The mean arterial pressure (MAP) was significantly higher in Group 1 at 0 minute, 1 minute and 3 minutes postintubation as compared with Group 2 and Group 3 (p=0.014). Three patients in Group 1, four patients in Group 2, and 10 patients in Group 3 developed hypotension and were treated with ephedrine, whereas five patients in Group 1 and one patient in Group 2 had hypertension after tracheal intubation. There was no significant difference between the groups with respect to the number of patients who received ephedrine boluses and in whom isoflurane had to be increased due to hypertension. No episode of bradycardia, tachycardia, dysrhythmia, or ST-T wave changes was reported. CONCLUSION: Gabapentin 800 mg in a single or double dose was equally effective in attenuating the hypertensive response to laryngoscopy and tracheal intubation in treated hypertensive patients.
OBJECTIVE: Transversus abdominis plane (TAP) block is a recently introduced regional anesthesia technique that is used for postoperative pain reduction in some abdominal surgeries. The present study evaluated the efficac...OBJECTIVE: Transversus abdominis plane (TAP) block is a recently introduced regional anesthesia technique that is used for postoperative pain reduction in some abdominal surgeries. The present study evaluated the efficacy of the TAP block on the post laparoscopic cholecystectomy pain intensity and analgesic consumption. METHODS: Fifty-four patients were enrolled in three groups: TAP block with normal saline (Group 1, n = 18); TAP block with bupivacaine (Group 2, n = 18); and TAP block with bupivacaine plus sufentanil (Group 3, n = 18). The time to the first fentanyl request, fentanyl consumption in the 24 hours following surgery, and postoperative pain intensity at 30 minutes, 1 hour, 6 hours, 12 hours, and 24 hours following discharge for recovery were measured and recorded. RESULTS: The total amount of 24-hour fentanyl consumption was higher in Group 1 (877.8 ± 338.8 μg) than either Group 2 (566.7 ± 367.8 μg) or Group 3 (555.5 ± 356.8 μg; p = 0.03). Postoperative pain score was higher in Group 1 than intervention groups (p = 0.006); however, there was no significant difference in intervention groups. The time to the first fentanyl request in Group 1 (79.44 ± 42.2) was significantly lower than Group 3 (206.38 ± 112.7; p = 0.001). CONCLUSION: The present study demonstrated that bilateral TAP block with 0.5% bupivacaine reduces post laparoscopic cholecystectomy pain intensity and fentanyl request and prolongs time to the first analgesic request. Adding sufentanil to the block solution reduced neither pain intensity nor fentanyl further consumption.
An increasing body of evidence shows that the choice of anesthetic can strongly influence more than simply the quality of anesthesia. Regional and general anesthesia have often been compared to ascertain whether one prov...An increasing body of evidence shows that the choice of anesthetic can strongly influence more than simply the quality of anesthesia. Regional and general anesthesia have often been compared to ascertain whether one provides benefits through dampening the stress response or harms by accelerating cancer progression. Regional anesthesia offers considerable advantages, by suppressing cortisol and catecholamine levels and reducing muscle breakdown postoperatively. It also has less immunosuppressive effect and potentially reduces the proinflammatory cytokine response. As such, vital organ functions (e.g., brain and kidney) may be better preserved with regional anesthetics, however, further study is needed. Volatile general anesthetics appear to promote cancer malignancy in comparison to regional and intravenous general anesthetics, and reduce the body's ability to act against cancer cells by suppression of natural killer cell activity. There is not sufficient evidence to support an alteration of current clinical practice, however, further research into this area is warranted due to the potential implications elicited by current studies.
OBJECTIVES: We have previously shown that vasopressin could inhibit the upregulation of inflammatory mediators. Expression of inflammatory mediators is tightly regulated by the upstream transcriptional pathway mitogen-ac...OBJECTIVES: We have previously shown that vasopressin could inhibit the upregulation of inflammatory mediators. Expression of inflammatory mediators is tightly regulated by the upstream transcriptional pathway mitogen-activated protein kinases (MAPKs) and activated protein-1 (AP-1). In this study, we elucidated whether vasopressin could inhibit the upregulation of MAPKs/AP-1. METHODS: Murine macrophages (RAW264.7 cells) randomly received lipopolysaccharide (LPS; 100 ng/mL) or LPS plus vasopressin (1000 pg/mL) (designated as the LPS and the LPS+V groups, respectively). Control groups were run simultaneously. For MAPKs, cells were harvested at 0 minutes, 15 minutes, 30 minutes, 45 minutes, and 60 minutes after reaction. For AP-1, cells were harvested at 60 minutes after reaction. Between-group differences in MAPKs (i.e., extracellular regulated kinase, c-Jun N-terminal kinase, and p38 MAPK) and AP-1 expressions were compared. RESULTS: Immunoblotting assay data revealed that extracellular regulated kinase concentrations of the LPS+V group that harvested at 45 minutes and 60 minutes, but not at 15 minutes and 30 minutes, were significantly lower than those of the LPS group (p=0.005 and p=0.013). C-Jun N-terminal kinase concentrations of the LPS+V group that harvested at 15 minutes, 30 minutes, 45 minutes, and 60 minutes were also significantly lower than those of the LPS group (all p<0.001). Concentrations of p38 MAPK of the LPS+V group that harvested at 15 minutes, 30 minutes, and 45 minutes, but not at 60 minutes, were also significantly lower than those of the LPS group (all p<0.001). In addition, immunohistochemistry assay revealed that the AP-1 fluorescence signals of the LPS+V group were weaker than those of the LPS group. CONCLUSION: Vasopressin inhibits MAPKs and AP-1 in endotoxin-activated macrophages.
Acute and chronic subdural hemorrhage in a 33 year old woman with severe headache from occipital to frontal regions and dull neck pain was diagnosed on magnetic resonance image, which revealed cerebrospinal fluid leakage...Acute and chronic subdural hemorrhage in a 33 year old woman with severe headache from occipital to frontal regions and dull neck pain was diagnosed on magnetic resonance image, which revealed cerebrospinal fluid leakage at C2-3 with spontaneous intracranial hypotension. Successful treatment was performed by epidural blood patch from the level of T7-T8 with injection of 20 mL of autologous blood.
Pain is a global epidemic, exacerbated by barriers to access of opioid analgesics. Regulations about opioids attempt to protect public health from the risks of harmful use of opioids, diversion, and dependence. Transderm...Pain is a global epidemic, exacerbated by barriers to access of opioid analgesics. Regulations about opioids attempt to protect public health from the risks of harmful use of opioids, diversion, and dependence. Transdermal buprenorphine is an effective opioid analgesic agent with unique properties that may make it particularly well suited for more widespread use. It is a versatile analgesic product with demonstrated safety and effectiveness in cancer and noncancer pain populations. Its pharmacological properties make it a first-line opioid analgesic for geriatric patients and patients with renal dysfunction; no dosing adjustments need to be made. The 7-day transdermal delivery system is convenient for patients and promotes compliance. A low dose of buprenorphine can provide effective and well-tolerated pain relief. Although buprenorphine has been associated with certain opioid-related adverse effects, such as dizziness and nausea, it is associated with a lower rate of constipation than many other opioid analgesics. The potential for nonmedical use of buprenorphine is relatively low compared with other opioid agents. Buprenorphine has a relatively low likeability for nonmedical use and the transdermal matrix patch renders the substance particularly difficult to extract for illicit purposes.
OBJECTIVES: Currently there are no reports of the effect of increasing heart rate (HR) induced by intravenous atropine on stroke volume variation (SVV). We hypothesized that increasing HR alters the value of SVV. This pr...OBJECTIVES: Currently there are no reports of the effect of increasing heart rate (HR) induced by intravenous atropine on stroke volume variation (SVV). We hypothesized that increasing HR alters the value of SVV. This prospective study aimed to investigate changes in SVV values by increasing HR induced by intravenous atropine in patients with good cardiac function. We also re-evaluated the effect of intravenous atropine alone on hemodynamics including new hemodynamic parameters such as SVV. METHODS: Patients were chosen as participants of this study if, 30 minutes after anesthesia induction, HR was below 65 beats/min. Baseline hemodynamic values were recorded, and then the patients received intravenous atropine (0.01 mg/kg; max 0.5 mg). These values were recorded again after intravenous atropine every minute for 5 minutes. RESULTS: Ten American Society of Anesthesiologists (ASA) physical status I-II patients aged 37-65 years who were scheduled for elective surgery were included. Intravenous atropine significantly increased HR at the 1-5 minute time points, mean arterial pressure at the 1-4 minute time points, and cardiac output at the 1-3 minute time points compared with baseline values but did not significantly change SVV, stroke volume index, pressure of end-tidal CO2, and systemic vascular resistance. CONCLUSION: Administration of intravenous atropine did not change SVV, and we present this as a novel finding.
Surgical procedures require general anesthesia using combinations of drugs including fentanyl and/or lidocaine. Because many of these drugs have bimodal anticonvulsant/proconvulsant effects, they must be administered car...Surgical procedures require general anesthesia using combinations of drugs including fentanyl and/or lidocaine. Because many of these drugs have bimodal anticonvulsant/proconvulsant effects, they must be administered carefully. We herein report a case of seizure attack during anesthesia induction with low-dose fentanyl and lidocaine in a young child with no history of seizures. A 10-year-old girl was scheduled to receive an elective tenectomy. After a few seconds of fentanyl and lidocaine administration for anesthesia induction, she developed generalized tonic-clonic seizures. Seizures subsided spontaneously after 3 minutes. The patient's blood sugar, serum electrolytes, and arterial blood gas analysis were normal immediately after the event. She remained hemodynamically stable; however, the surgery was postponed after communication and discussion with the surgeon. Postoperatively, there was no evidence of postictal phase, and serum electrolytes and magnetic resonance imaging of the brain were normal. The patient had an uneventful recovery. However, electroencephalogram showed that hyperventilation stimulation test induced isolated epileptiform spikes over O1, suggesting a potential paroxysmal disorder over the left occipital area. This report is on a rare complication likely caused by fentanyl or lidocaine, which suggests that these drugs should be used cautiously in children whose clinical epileptic activities have been verified or are strongly suspected.
Anesthetics and psychoactive drugs could relieve diseases, if used properly. However, they can cause dependency, and their misuse or abuse could adversely affect people's health and social stability. For a long time, the...Anesthetics and psychoactive drugs could relieve diseases, if used properly. However, they can cause dependency, and their misuse or abuse could adversely affect people's health and social stability. For a long time, the Chinese government has been reinforcing the regulation on anesthetics and psychoactive drugs to ensure their legal and proper usage, and to prevent abuse. The state council issued 'the regulations on the administration of anesthetic drugs and psychotropic drugs' in 2005, based on which a legal system was established for administration of anesthetics and psychoactive drugs with the objectives of ensuring their legitimate medical utilization, and preventing illegal abuse.
In this commentary on the medical use and regulation of transdermal buprenorphine we bring together our complimentary perspectives on the neuropharmacology of analgesics (Dr. Henningfield) and clinical medicine to addres...In this commentary on the medical use and regulation of transdermal buprenorphine we bring together our complimentary perspectives on the neuropharmacology of analgesics (Dr. Henningfield) and clinical medicine to address the needs of people with pain (Dr. Sun). Together, the neuropharmacology of buprenorphine, the clinical and abuse deterring benefits of the 7-day transdermal formulation, the low rates of harmful use and abuse detected in post-marketing surveillance studies, and the desirable clinical benefits in the elderly, in persons with compromised kidney function, and other populations support the regulation of buprenorphine comparable to tramadol-like analgesics. We support this approach and believe that it strikes the right balance of control to provide appropriate access to people with pain and their health providers, while still providing the basis for deterring harmful use and abuse.
There is a global crisis in access to pain management in the world. WHO estimates that 4.65 billion people live in countries where medical opioid consumption is near to zero. For 2010, WHO considered a per capita consump...There is a global crisis in access to pain management in the world. WHO estimates that 4.65 billion people live in countries where medical opioid consumption is near to zero. For 2010, WHO considered a per capita consumption of 216.7 mg morphine equivalents adequate, while Taiwan had a per capita consumption of 0.05 mg morphine equivalents in 2007. In Asia, the use of opioids is sensitive because of the Opium Wars in the 19th century and for this reason, the focus of controlled substances policies has been on the prevention of diversion and dependence. However, an optimal public health outcome requires that also the beneficial aspects of these substances are acknowledged. Therefore, WHO recommends a policy based on the Principle of Balance: ensuring access for medical and scientific purposes while preventing diversion, harmful use and dependence. Furthermore, international law requires that countries ensure access to opioid analgesics for medical and scientific purposes. There is evidence that opioid analgesics for chronic pain are not associated with a major risk for developing dependence. Barriers for access can be classified in the categories of overly restrictive laws and regulations; insufficient medical training on pain management and problems related to assessment of medical needs; attitudes like an excessive fear for dependence or diversion; and economic and logistical problems. The GOPI project found many examples of such barriers in Asia. Access to opioid medicines in Taiwan can be improved by analysing the national situation and drafting a plan. The WHO policy guidelines Ensuring Balance in National Policies on Controlled Substances can be helpful for achieving this purpose, as well as international guidelines for pain treatment.
Pain is a burdensome symptom that can commonly exist chronically along the cancer trajectory. Uncontrolled pain will impact on cancer patients' quality of life, even further negatively affect cancer survivors' employment...Pain is a burdensome symptom that can commonly exist chronically along the cancer trajectory. Uncontrolled pain will impact on cancer patients' quality of life, even further negatively affect cancer survivors' employment. Based on systemic reviews of studies for past 10 years, the paper reported that although there is enormous advancement on the knowledge of cancer pain and pain management, studies still documented undertreatment of cancer pain globally. Additionally, pain distress a significant portion of cancer survivors. The pain in cancer survivors distinct from the pain related with cancer, instead emphasize on pain related with cancer treatment, such as neuropathic pain, muscular syndrome. Evidence-based pain management with common pain problems in cancer survivors is lacking. Further studies are needed to understand the pain in cancer survivors and to develop effective strategies in helping cancer survivors to manage their pain.
Pain management is typically more developed in western countries compared to Asia. From the accreditation standard of the Joint Commission International (JCI), there is a broad scope for pain management. In 2008, our med...Pain management is typically more developed in western countries compared to Asia. From the accreditation standard of the Joint Commission International (JCI), there is a broad scope for pain management. In 2008, our medical center established the pain management policy, and the goal is to be a pain-free medical facility. The Framework of Pain Management Policy including: 1. the rights of patients and family members 2. Employee education 3. Assessment of pain (screening, evaluating, monitoring) 4. Patient care of pain. After implementation of pain management program, the compliance of pain assessment, the analysis of pain score before and after pain management and the analysis of Pain Management Index (PMI), all showed improvement in pain management program. The consumption of opioids usage steadily increased from 2010 to 2014. The success of our pain management program implementation could be attributed to the clear pain management policy, the firm support of higher leadership, the cooperation of IT department, and the quality control.
In order to strengthen the management system of medical and scientific use of controlled drugs, Taiwan government referred to the three major drug control treaties of United Nation to formulate the "Controlled Drugs Act"...In order to strengthen the management system of medical and scientific use of controlled drugs, Taiwan government referred to the three major drug control treaties of United Nation to formulate the "Controlled Drugs Act" in 1999. There are three kinds of system to manage controlled drugs, including (1) Schedule Management, (2) Licensing Regulation Management and (3) Diversion Control Management, such as the reporting and auditing systems. In this article, the management system of controlled drugs will be discussed thoroughly. Under the "Controlled Drugs Act", the controlled drugs are scheduled by the tendency of their habitual use, drug dependency, abuse, and social hazard. If violating the rule, the administrative sanction is applied. Cases of violations will also be given in this article.
OBJECTIVE: This study was aimed to explore the pharmacoepidemiology of chronic noncancer pain (CNCP) patients who required chronic opioid therapy (COT) in the Taiwanese population. METHODS: Using the Taiwan National Heal...OBJECTIVE: This study was aimed to explore the pharmacoepidemiology of chronic noncancer pain (CNCP) patients who required chronic opioid therapy (COT) in the Taiwanese population. METHODS: Using the Taiwan National Health Insurance Research Database during 2008-2009, COT-requiring CNCP patients were identified by the inclusion criteria of both chronic analgesic requirement for >3 months per year and long-term use of controlled opioids for >28 therapeutic days during any 3-month period in ambulatory visits with malignancy-related pain excluded. Their demographic data and pharmacoepidemiological characteristics of opioid consumption and opioid prescriptions issued in ambulatory visits were analyzed. RESULTS: In total, 159 patients were enrolled as COT-requiring CNCP patients, and the prevalence was calculated at 0.016% in a 2-year period. Females were outnumbered by males (45.3% vs. 54.7%). Almost 60% of them were of working age and 93.7% belonged to low-income households, as in the health insurance claims, probably implying socioeconomic disadvantages associated with CNCP. The leading three diagnoses were unspecified myalgia and myositis, lumbago, and abdominal pain of unspecified site. The most common department from where these 159 CNCP patients obtained their opioid prescriptions was the emergency department (27.6%), ensued by a pain clinic (25.3%), but they could acquire only a few opioid therapeutic days through emergency department visits. Moreover, pain clinic satisfied the majority of opioid therapeutic days. Among all opioids, morphine was the most frequently prescribed in opioid-obtaining ambulatory visits, accounting for most of the opioid therapeutic days as well as opioid consumption. CONCLUSION: COT-requiring CNCP patients were easily associated with adverse socioeconomic liabilities and often visited emergency department as well as pain clinics. Morphine was the main opioid used for their chronic pain. Transfer of COT-requiring CNCP patients to appropriate departments is strongly recommended for efficient long-term pharmacotherapy for their chronic pain.
Limiting the intracuff pressure of a laryngeal mask airway (LMA) to <60 cmH2O is recommended in clinical practice. This report aimed to assess the efficacy of a modified syringe technique to adjust the intracuff pressure...Limiting the intracuff pressure of a laryngeal mask airway (LMA) to <60 cmH2O is recommended in clinical practice. This report aimed to assess the efficacy of a modified syringe technique to adjust the intracuff pressure of an LMA. In a preclinical study, commercially available 20-mL syringes were attached to the pilot balloon of LMAs with different preset intracuff pressures (40 cmH2O, 50 cmH2O, 60 cmH2O, 70 cmH2O, 80 cmH2O, 100 cmH2O, and 120 cmH2O). After attachment, the syringe plunger was allowed to passively rebound. If no rebound of the plunger was observed after attachment, 1 mL of air was withdrawn and the plunger was allowed to passively rebound again. This technique allowed the plunger to overcome static friction and avoid excessive deflation of the LMA cuffs. The intracuff pressure was measured using a manometer after the plunger ceased moving. In the preclinical study, the intracuff pressure was always less than or close to 60 cmH2O after adjustment using this modified syringe technique. After evaluating the performance and characteristics of the syringe in the preclinical study, we concluded that the modified syringe technique may be useful for adjusting LMA intracuff pressure effectively.