Objective To investigate the 50% effective dose(ED)and 95% effective dose(ED)of dexmedetomidine(DEX)combined with 0.032 μg/(kg·h)sufentanil as well as its analgesic effect for patient-controlled intravenous analgesia(PCIA)after video-assisted thoracoscopic surgery(VATS).Methods Totally 25 patients undergoing elective VATS were enrolled. DEX and 0.032 μg/(kg·h)sufentanil were used for postoperative PCIA. The loading dose of DEX was 0.048 μg/(kg·h),and the dose difference between two adjacent patients was 0.008 μg/(kg·h). The DEX dose of a current patient was determined by whether the previous patient was satisfied with postoperative analgesic effect. If the previous patient was satisfied with postoperative analgesic effect,the DEX dose of the current patient was decreased by 0.008 μg/(kg·h);and if the previous analgestic effect was not satisfactory,DEX dose of the current patient was increased by 0.008 μg/(kg·h). The study endpoint was dexmedetomidine dose was<0.008 μg/(kg· h) within 7 upper and lower cycles in 7 consecutive cases. Finally,the probability unit regression was used to estimate the ED and ED of DEX and their 95% .Results When DEX combined with 0.032 μg/(kg·h) sufentanil was used for postoperative PCIA in young patients undergoing VATS,the ED and EDof DEX were 0.0346 μg/(kg· h)[95%:0.0283-0.0408 μg/(kg·h)] and 0.0459 μg/(kg·h)[95%:0.0400-0.0880 μg/(kg·h)],respectively. No adverse reaction such as vomiting,respiratory depression,or bradycardia occurred. The average Visual Analogue Scale(VAS)scores at rest(=-5.128,=0.000)and cough(Z=-6.642,=0.000)and the Ramsay sedation score(Z=-2.335,=0.020)within 6 hours after surgery were higher than those after 6 hour.Conclusion DEX combined with 0.032 μg/(kg·h) sufentanil are effective for postoperative PCIA in patients undergoing VATS when the ED and ED are 0.0346 μg/(kg·h)and 0.0459 μg/(kg·h),respectively.
Analgesia, Patient-Controlled ; Analgesics, Non-Narcotic ; administration & dosage ; therapeutic use ; Dexmedetomidine ; administration & dosage ; therapeutic use ; Dose-Response Relationship, Drug ; Drug Therapy, Combination ; Humans ; Pain, Postoperative ; drug therapy ; Sufentanil ; administration & dosage ; therapeutic use ; Thoracic Surgery, Video-Assisted

Nefopam has a pharmacologic profile distinct from that of opioids or other anti-inflammatory drugs. Several recent studies demonstrate that nefopam has a mechanism of action similar to those of anti-depressants and anticonvulsants for treating neuropathic pain. The present study investigates the mechanical antiallodynic effect of nefopam using immunohistochemical study and western blot analysis in a rat neuropathic pain model. Twenty-eight male Sprague-Dawley rats were subjected to left fifth lumbar (L5) spinal nerve ligation and intrathecal catheter implantation, procedures which were not performed on the 7 male Sprague-Dawley rats in the sham surgery group (group S). Nefopam, either 10 or 100 microg/kg (group N10 or N100, respectively), and normal saline (group C) were intrathecally administered into the catheter every day for 14 days. The mechanical allodynic threshold of intrathecal nefopam was measured using a dynamic plantar aesthesiometer. Immunohistochemistry targeting cluster of differentiation molecule 11b (CD11b) and glial fibrillary acidic protein (GFAP) was performed on the harvested spinal cord at the level of L5. Extracellular signal-regulated kinase 1/2 (ERK 1/2) and cyclic adenosine monophosphate response element binding protein (CREB) were measured using western blot analysis. The N10 and N100 groups showed improved mechanical allodynic threshold, reduced CD11b and GFAP expression, and attenuated ERK 1/2 and CREB in the affected L5 spinal cord. In conclusion, intrathecal nefopam reduced mechanical allodynia in a rat neuropathic pain model. Its mechanical antiallodynic effect is associated with inhibition of glial activation and suppression of the transcription factors' mitogen-activated protein kinases in the spinal cord.
Analgesics, Non-Narcotic/administration & dosage ; Animals ; Dose-Response Relationship, Drug ; Hyperalgesia/*drug therapy/etiology/*physiopathology ; Injections, Spinal ; Male ; Nefopam/*administration & dosage ; Neuralgia/complications/*drug therapy/*physiopathology ; Pain Measurement/drug effects ; Pain Perception/*drug effects ; Rats ; Rats, Sprague-Dawley ; Treatment Outcome

Nefopam (NFP) is a non-opioid, non-steroidal, centrally acting analgesic drug that is derivative of the non-sedative benzoxazocine, developed and known in 1960s as fenazocine. Although the mechanisms of analgesic action of NFP are not well understood, they are similar to those of triple neurotransmitter (serotonin, norepinephrine, and dopamine) reuptake inhibitors and anticonvulsants. It has been used mainly as an analgesic drug for nociceptive pain, as well as a treatment for the prevention of postoperative shivering and hiccups. Based on NFP's mechanisms of analgesic action, it is more suitable for the treatment of neuropathic pain. Intravenous administration of NFP should be given in single doses of 20 mg slowly over 15-20 min or with continuous infusion of 60-120 mg/d to minimize adverse effects, such as nausea, cold sweating, dizziness, tachycardia, or drowsiness. The usual dose of oral administration is three to six times per day totaling 90-180 mg. The ceiling effect of its analgesia is uncertain depending on the mechanism of pain relief. In conclusion, the recently discovered dual analgesic mechanisms of action, namely, a) descending pain modulation by triple neurotransmitter reuptake inhibition similar to antidepressants, and b) inhibition of long-term potentiation mediated by NMDA from the inhibition of calcium influx like gabapentinoid anticonvulsants or blockade of voltage-sensitive sodium channels like carbamazepine, enable NFP to be used as a therapeutic agent to treat neuropathic pain.
Administration, Intravenous ; Administration, Oral ; Analgesia ; Analgesics, Non-Narcotic ; Anticonvulsants ; Antidepressive Agents ; Calcium ; Carbamazepine ; Dizziness ; Drug-Related Side Effects and Adverse Reactions ; Hiccup ; Long-Term Potentiation ; Molecular Mechanisms of Pharmacological Action ; N-Methylaspartate ; Nausea ; Nefopam* ; Neuralgia* ; Neurotransmitter Agents ; Nociceptive Pain ; Norepinephrine ; Shivering ; Sleep Stages ; Sodium Channels ; Sweat ; Sweating ; Tachycardia

OBJECTIVEWe evaluated a new hypothesis of acetaminophen therapy to reduce the necessity of imaging in patients with probable traumatic cervical spine injury.

METHODSPatients with acute blunt trauma to the neck and just posterior midline cervical tenderness received acetaminophen (15 mg/kg) intravenously after cervical spine immobilization. Then, all the patients underwent plain radiography and computerized tomography of the cervical spine. The outcome measure was the presence of traumatic cervical spine injury. Sixty minutes after acetaminophen infusion, posterior midline cervical tenderness was reassessed.

RESULTSOf 1 309 patients, 41 had traumatic cervical spine injuries based on imaging. Sixty minutes after infusion, posterior midline cervical tenderness was eliminated in 1 041 patients, none of whom had abnormal imaging.

CONCLUSIONPatients with cervical spine trauma do not need imaging if posterior midline cervical tenderness is eliminated after acetaminophen infusion. This analgesia could be considered as a diagnostic and therapeutic intervention.

Acetaminophen ; administration & dosage ; Adolescent ; Adult ; Analgesics, Non-Narcotic ; administration & dosage ; Female ; Humans ; Iran ; Longitudinal Studies ; Male ; Middle Aged ; Neck Injuries ; diagnostic imaging ; drug therapy ; Prospective Studies ; Radiography ; Spinal Injuries ; diagnostic imaging ; drug therapy ; Unnecessary Procedures ; Wounds, Nonpenetrating ; diagnostic imaging ; drug therapy

PURPOSE: Toxicity caused by acetaminophen and its toxic mechanisms in the liver have been widely studied, including effects involving metabolism and oxidative stress. However, its adverse effects on heart have not been sufficiently investigated. This study evaluated the cardiac influence and molecular events occurring within the myocardium in rats treated with a dose of acetaminophen large enough to induce conventional liver damage. MATERIALS AND METHODS: Male rats were orally administered a single dose of acetaminophen at 1,000 mg/kg-body weight, and subsequently examined for conventional toxicological parameters and for gene expression alterations to both the heart and liver 24 hours after administration. RESULTS: Following treatment, serum biochemical parameters including aspartate aminotransferase and alanine aminotransferase were elevated. Histopathological alterations of necrosis were observed in the liver, but not in the heart. However, alterations in gene expression were observed in both the liver and heart 24 hours after dosing. Transcriptional profiling revealed that acetaminophen changed the expression of genes implicated in oxidative stress, inflammatory processes, and apoptosis in the heart as well as in the liver. The numbers of up-regulated and down-regulated genes in the heart were 271 and 81, respectively, based on a two-fold criterion. CONCLUSION: The induced expression of genes implicated in oxidative stress and inflammatory processes in the myocardium reflects molecular levels of injury caused by acetaminophen (APAP), which could not be identified by conventional histopathology.
Acetaminophen/*toxicity ; Administration, Oral ; Analgesics, Non-Narcotic/*toxicity ; Animals ; Drug-Induced Liver Injury/pathology/*physiopathology ; Gene Expression Profiling ; Heart/*physiology ; Liver/pathology/physiology ; Male ; Myocardium/pathology ; Rats ; Transcriptome/*drug effects

A high sensitive and rapid method was developed for the analysis of lappaconitine in mouse plasma using liquid chromatography coupled to mass spectrometry (LC-MS). Detection was performed by positive ion electrospray ionization (ESI) in multiple reaction monitoring (MRM) mode, monitoring the transitions m/z 585 --> m/z 535 and m/z 356 --> m/z 192, for the quantification of lappaconitine and tetrahydropalmatine (internal standard, IS), respectively. The method was linear over the concentration range of 3.0-2000.0 ng x mL(-1). The lower limit of quantification was 3.0 ng x mL(-1). Intra- and inter-run precisions (RSD) were both less than 9.9% and accuracy (RE) within +/- 4.8%. After single intravenous injections of lappaconitine hydrobromide at 1.0, 2.0 and 4.0 mg x kg(-1), the elimination half-lives (t(1/2)) were 0.47, 0.48 and 0.49 h, and the areas under the curve (AUC(0-t)) were 55.5, 110.5 and 402.9 ng x h x mL(-1), separately. The pharmacokinetic profile of lappaconitine was linear at relatively lower dose levels (1.0-2.0 mg x kg(-1)). When the dose increased farther to 4.0 mg x kg(-1), the Vz and CL decreased, and the increase fold of the AUC was much larger than that of the dose.
Aconitine ; administration & dosage ; analogs & derivatives ; chemistry ; pharmacokinetics ; Analgesics, Non-Narcotic ; administration & dosage ; chemistry ; pharmacokinetics ; Animals ; Area Under Curve ; Chromatography, Liquid ; methods ; Injections, Intravenous ; Male ; Mice ; Molecular Structure ; Spectrometry, Mass, Electrospray Ionization ; methods

OBJECTIVETo investigate the effects of administration of dexmedetomidine in anaesthesia for esophageal cancer operation.

METHODS100 patients (ASAI-II) who were undergoing to esophageal cancer operation were randomly divided into control group (group A) and dexmedetomidine group (group B) (n = 50). The scheme of induction and maintenance of aesthesia of the two groups were identical. Patients in group B administered dexmedetomidine at a dose of 1 microg/kg over 10 min and patients in group A were given a placebo infusion of normal saline. Patients in group B administered dexmedetomidine at a dose of 0.4 microg/(kg x h) was injected and stoped at 30 min by the end of operation. Mean artery pressure (MAP) and heart rate (HR) were detected before induction (T0), induction (T1), 1 min after extubation (T2), 5 min after extubation (T3) and 10 min after extubation (T4) Propofol comsumption, fentanlyl comsumption, and side effects were recorded as well.

RESULTSThe results showed that MAP and HR (T0, T1, T2, T3, T4) in group B were significantly different from those in group A which fluctuated more markedly (P < 0.05). Propofol comsumption in group A was much more than that in group B (P < 0.05). Incidence of pharynx and larynx ache and restlessness were higher in group A than those in group B (P < 0.05).

CONCLUSIONDexmedetomidine could effectively reduce the cardiovascular response to incubation and extubation in esophageal cancer operation patients. Propofol comsumption, fentanlyl comsumption and side effects were reduceed as well.

Adjuvants, Anesthesia ; administration & dosage ; Adult ; Aged ; Analgesics, Non-Narcotic ; administration & dosage ; Anesthetics, Intravenous ; administration & dosage ; Dexmedetomidine ; administration & dosage ; Esophageal Neoplasms ; surgery ; Female ; Fentanyl ; administration & dosage ; Humans ; Male ; Middle Aged ; Propofol ; administration & dosage

Biodegradable four-arm star-shaped poly(ethylene glycol)-block-poly(L-lactic acid) copolymer (sPEG-b-PLLA), four-arm star-shaped poly(L-lactic acid) (sPLLA), linearly poly(ethylene glycol)-block-poly(L-lactic acid) copolymer (PEG-b-PLLA) and linearly poly(L-lactic acid) (PLLA) were synthesized from L-lactice acid, pentaerythritol, poly(ethylene glycol) and star-shaped poly(ethylene glycol), using the method of melt polycondensation, and the products were characterized and confirmed by 1H NMR spectroscopy, FT-IR and GPC. Four types of ibuprofen loaded microspheres based on the above four types of polymers, i.e., IBU/PLLA, IBU/sPLLA, IBU/PEG-b-PLLA, and IBU/sPEG-b-PLLA microspheres were prepared using the method of solvent evaporation, and the optimized preparation technology was obtained via orthogonal experiments, and the drug-encapsulating properties and in vitro drug-releasing properties were studied. The results showed that compared with IBU/PLLA and IBU/PEG-b-PLLA microspheres, the drug encapsulate efficiency of IBU/sPLLA and IBU/sPEG-b-PLLA microspheres were higher and the in vitro drug releasing rate slowed down, which mainly due to the faster degradation of sPLLA and sPEG-b-PLLA for the star-shaped structure and the block copolymerization of sPEG. The drug releasing curves of these three types of microspheres could be fit by first-order equation, and the releasing mechanism was non-Fickian diffusing, i.e., the synergetic effect of polymer degradation and drug diffusion.
Analgesics, Non-Narcotic ; administration & dosage ; chemistry ; Anti-Inflammatory Agents, Non-Steroidal ; administration & dosage ; chemistry ; Delayed-Action Preparations ; Drug Carriers ; Ibuprofen ; administration & dosage ; chemistry ; Lactates ; chemistry ; Lactic Acid ; chemistry ; Magnetic Resonance Spectroscopy ; Microspheres ; Particle Size ; Polyesters ; Polyethylene Glycols ; chemistry ; Polymers ; chemistry ; Spectroscopy, Fourier Transform Infrared

OBJECTIVETo investigate the postoperative analgesic effect of parecoxib sodium in patients with posterior spinal surgery.

METHODSEighty patients undergoing posterior spinal surgery under general anesthesia were randomly divided into parecoxib sodium group and placebo group (n=40). All the patients received a single dose of m ml morphine (1.0 mg/ml) as the background analgesia immediately after the operation. The patients in parecoxib sodium group were given 40 mg parecoxib sodium intravenously, and those in the placebo group received an equivalent volume of saline instead, and at 24 and 48 h after the operation, the same dose was repeated. The visual analog pain score, patient satisfaction and adverse reactions were recorded after the administrations.

RESULTSCompared with the placebo group, the patients in parecoxib sodium group had significantly lowered VAS score at 6, 12, 24, and 48 h after the operation (P<0.05). No significant differences were noted in the patient satisfaction and adverse reactions between the two groups.

CONCLUSIONPostoperative short-term use of parecoxib sodium can can provide good postoperative analgesic effect in patients undergoing posterior spinal surgery.

Analgesics, Non-Narcotic ; therapeutic use ; Anesthesia, General ; Cyclooxygenase 2 Inhibitors ; therapeutic use ; Female ; Humans ; Injections, Intravenous ; Isoxazoles ; administration & dosage ; therapeutic use ; Male ; Pain, Postoperative ; drug therapy ; Spinal Diseases ; surgery

PURPOSE: The aim of the study was to compare the efficacy of parecoxib for postoperative analgesia after endoscopic turbinate and sinus surgery with the prodrug of acetaminophen, proparacetamol. MATERIALS AND METHODS: Fifty American Society of Anesthesiology (ASA) physical status I-II patients, receiving functional endoscopic sinus surgery (FESS) and endoscopic turbinectomy, were investigated in a prospective, randomized, double-blind manner. After local infiltration with 1% mepivacaine, patients were randomly allocated to receive intravenous (IV) administration of either 40mg of parecoxib (n=25) or 2g of proparacetamol (n=25) 15 min before discontinuation of total IV anaesthesia with propofol and remifentanil. A blinded observer recorded the incidence and severity of pain at admission to the post anaesthesia care unit (PACU) at 10, 20, and 30 min after PACU admission, and every 1 h thereafter for the first 6 postoperative h. RESULTS: The area under the curve of VAS (AUC(VAS)) calculated during the study period was 669 (28-1901) cm·min in the proparacetamol group and 635 (26-1413) cm·min in the parecoxib group (p=0.34). Rescue morphine analgesia was required by 14 patients (56%) in the proparacetamol group and 12 patients (48%) in the parecoxib (p> or=0.05), while mean morphine consumption was 5-3.5mg and 5-2.0mg in the proparacetamol groups and parecoxib, respectively (p> or=0.05). No differences in the incidence of side effects were recorded between the 2 groups. Patient satisfaction was similarly high in both groups, and all patients were uneventfully discharged 24h after surgery. CONCLUSION: In patients undergoing endoscopic nasal surgery, prior infiltration with local anaesthetics, parecoxib administered before discontinuing general anaesthetic, is not superior to proparacetamol in treating early postoperative pain.
Acetaminophen/administration & dosage/analogs & derivatives/*therapeutic use ; Adult ; Analgesics, Non-Narcotic/administration & dosage/therapeutic use ; Cyclooxygenase Inhibitors/administration & dosage/therapeutic use ; Double-Blind Method ; Endoscopy/methods ; Female ; Humans ; Infusions, Intravenous ; Injections, Intravenous ; Isoxazoles/administration & dosage/*therapeutic use ; Male ; Middle Aged ; Nasal Polyps/surgery ; Pain, Postoperative/*drug therapy ; Prodrugs/administration & dosage/*therapeutic use ; Prospective Studies ; Sinusitis/surgery ; Treatment Outcome