Role of vasopressin in current anesthetic practice.

Arginine vasopressin (AVP), also known as antidiuretic hormone, is a peptide endogenously secreted by the posterior pituitary in response to hyperosmolar plasma or systemic hypoperfusion states. When administered intravenously, it causes an intense peripheral vasoconstriction through stimulation of V1 receptors on the vascular smooth muscle. Patients in refractory shock associated with severe sepsis, cardiogenic or vasodilatory shock, or cardiopulmonary bypass have inappropriately low plasma levels of AVP ('relative vasopressin deficiency') and supersensitivity to exogenously-administered AVP. Low doses of AVP and its synthetic analog terlipressin can restore vasomotor tone in conditions that are resistant to catecholamines, with preservation of renal blood flow and urine output. They are also useful in the treatment of refractory arterial hypotension in patients chronically treated with renin-angiotensin system inhibitors, cardiac arrest, or bleeding esophageal varices. In the perioperative setting, they represent attractive adjunct vasopressors in advanced shock states that are unresponsive to conventional therapeutic strategies.

The role of inversely operating glutamate transporter in the paradoxical analgesia produced by glutamate transporter inhibitors.

Controlling extracellular glutamate level in a physiological range is important to maintain normal sensory transmission. Here, we investigated the paradoxical action of glutamate transporters in the rat formalin test to elucidate a possible role of inversely operating transporters in its analgesic mechanism. The effects of glutamate transporter inhibitor on formalin-induced pain behavior were examined. Then we performed a microdialysis study to clarify the differential change in extracellular glutamate concentration by intrathecal administration of transportable and non-transportable blockers. And we further investigated the mechanism pharmacologically via pretreatment with antagonists of various receptors and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling (TUNEL) staining. Intrathecally-injected glutamate transporter inhibitors, non-transportable DL-threo-ß-benzyloxyaspartat (TBOA) and transportable trans-pyrrolidine-2,4-dicarboxylic acid (t-PDC), produced paradoxical antinociception in the formalin test. In normal rats, inhibition of the glutamate transporter increased extracellular glutamate. In the formalin model rats, TBOA suppressed while t-PDC enhanced glutamate release. When tPDC was pretreated 30min prior to formalin injection, glutamate release was blocked. Blocking α-2 adrenergic receptors reversed the tPDC analgesia. Increased apoptosis was not apparent in the spinal dorsal horn of tPDC-treated rats compared to the control group. These data suggest that glutamate transporters in a formalin-induced pain state work in a reverse mode and can be blocked from releasing glutamate by TBOA and preloaded tPDC. The analgesic mechanism of TBOA may be related to the blockade of inversely operating transporter, and that of tPDC may be associated with the activation of noradrenergic neurotransmission but not with dorsal horn neurotoxicity.

Femoral nerve block for patient undergoing total knee arthroplasty: Prospective, randomized, double-blinded study evaluating analgesic effect of perineural fentanyl additive to local anesthetics.

BACKGROUND: The existence of peripheral opioid receptors and its effectiveness in peripheral nerve block remain controversial. The aim of this prospective, randomized, double-blinded study was to examine the analgesic effects of adding fentanyl to ropivacaine for continuous femoral nerve block (CFNB) using patient-controlled analgesia after total knee arthroplasty (TKA). METHODS: The patients were divided into 2 groups, each with n = 40 in ropivacaine (R) group and n = 42 in R with fentanyl (R + F) group. After operation, the patients in each group received R + F and R alone via a femoral nerve catheter, respectively. We assessed the visual analog scale (VAS) pain immediately before administration (baseline) and at 15, 30, and 60 minutes on postanesthesia care unit (PACU), and resting and ambulatory VAS score up to 24 hours. RESULTS: Overall, the average VAS scores in the R + F group were slightly lower than those of the R group. However, the VAS score differences between groups were not statistically significant, except for 30 minutes (P = 0.009) in PACU. R group showed higher supplemental analgesics consumption in average compared with R + F group, but not significant. CONCLUSION: Additional fentanyl did not show prominent enhancement of analgesic effect in the field of CFNB after TKA.

Effects of tianeptine on the development and maintenance of mechanical allodynia in a rat model of neuropathic pain.

We validate the analgesic efficacy of tianeptine by different administration routes and timing in a rat model of neuropathic pain. Neuropathic pain was induced by ligating the L5 and L6 spinal nerves in male Sprague-Dawley rats, and mechanical allodynia was assessed using von Frey filaments. The effects of orally administered tianeptine and pretreatment with tianeptine (intrathecally or intraperitoneally) on mechanical allodynia were assessed. Oral and preemptive intrathecal administration of tianeptine significantly increased the paw withdrawal threshold but preemptive intraperitoneal administration did not. Nevertheless, intraperitoneal pretreatment of tianeptine potentiated the antiallodynic effects of subsequently administered tianeptine. These findings suggest that tianeptine may be effective for preventing and treating neuropathic pain and that it can be used more widely in clinical pain practice.

The Role of Spinal Dopaminergic Transmission in the Analgesic Effect of Nefopam on Rat Inflammatory Pain.

BACKGROUND: Nefopam has been known as an inhibitor of the reuptake of monoamines, and the noradrenergic and/or serotonergic system has been focused on as a mechanism of its analgesic action. Here we investigated the role of the spinal dopaminergic neurotransmission in the antinociceptive effect of nefopam administered intravenously or intrathecally. METHODS: The effects of intravenously and intrathecally administered nefopam were examined using the rat formalin test. Then we performed a microdialysis study to confirm the change of extracellular dopamine concentration in the spinal dorsal horn by nefopam. To determine whether the changes of dopamine level are associated with the nefopam analgesia, its mechanism was investigated pharmacologically via pretreatment with sulpiride, a dopaminergic D2 receptor antagonist. RESULTS: When nefopam was administered intravenously the flinching responses in phase I of the formalin test were decreased, but not those in phase II of the formalin test were decreased. Intrathecally injected nefopam reduced the flinching responses in both phases of the formalin test in a dose dependent manner. Microdialysis study revealed a significant increase of the level of dopamine in the spinal cord by intrathecally administered nefopam (about 3.8 fold the baseline value) but not by that administered intravenously. The analgesic effects of intrathecally injected nefopam were not affected by pretreatment with sulpiride, and neither were those of the intravenous nefopam. CONCLUSIONS: Both the intravenously and intrathecally administered nefopam effectively relieved inflammatory pain in rats. Nefopam may act as an inhibitor of dopamine reuptake when delivered into the spinal cord. However, the analgesic mechanism of nefopam may not involve the dopaminergic transmission at the spinal level.

Anti-allodynic effect of intrathecal processed Aconitum jaluense is associated with the inhibition of microglial activation and P2X7 receptor expression in spinal cord.

BACKGROUND: For their analgesic and anti-arthritic effects, Aconitum species have been used in folk medicine in some East Asian countries. Although their analgesic effect is attributed to its action on voltage-dependent sodium channels, they also suppress purinergic receptor expression in dorsal root ganglion neurons in rats with neuropathic pain. In vitro study also demonstrated that the Aconitum suppresses ATP-induced P2X7 receptor (P2X7R)-mediated inflammatory responses in microglial cell lines. Herein, we examined the effect of intrathecal administration of thermally processed Aconitum jaluense (PA) on pain behavior, P2X7R expression and microglial activation in a rat spinal nerve ligation (SNL) model. METHODS: Mechanical allodynia induced by L5 SNL in Sprague-Dawley rats was measured using the von Frey test to evaluate the effect of intrathecal injection of PA. Changes in the expression of P2X7R in the spinal cord were examined using RT-PCR and Western blot analysis. In addition, the effect of intrathecal PA on microglial activation was evaluated by immunofluorescence. RESULTS: Intrathecal PA attenuated mechanical allodynia in a dose-dependent manner showing both acute and chronic effects with 65 % of the maximal possible effect. The expression and production of spinal P2X7R was increased five days after SNL, but daily intrathecal PA injection significantly inhibited the increase to the level of naïve animals. Immunofluorescence of the spinal cord revealed a significant increase in P2X7R expression and activation of microglia in the dorsal horn, which was inhibited by intrathecal PA treatment. P2X7R co-localized with microglia marker, but not neurons. CONCLUSIONS: Intrathecal PA exerts anti-allodynic effects in neuropathic pain, possibly by suppressing P2X7R production and expression as well as reducing microglial activation in the spinal cord.

An exploratory study on the effectiveness of "Calmare therapy" in patients with cancer-related neuropathic pain: A pilot study.

PURPOSE: Calmare therapy (CT) has been suggested as a novel treatment for managing chronic pain. Recently, it was reported to show a positive therapeutic outcome for managing neuropathic pain condition. We performed an exploratory prospective study on the effectiveness of CT in patients with various types of cancer-related neuropathic pain (CNP). METHOD: We performed an open-labeled, single-arm, exploratory study on the effectiveness of CT in patients with various types of cancer-related neuropathic pain (CNP). The primary endpoint was a comparison of the 11-point Numerical Rating Scale (NRS) pain score at one month with the baseline score in each patient. Brief Pain Inventory (BPI) and consumption of opioid were also evaluated during follow-up period. RESULTS: CT significantly decreased NRS pain score at one month from baseline (p < 0.001) in 20 patients with chemotherapy-induced peripheral neuropathy (n = 6), metastatic bone pain (n = 7), and post-surgical neuropathic pain (n = 7). It also improved overall BPI scores, decreased consumption of rescue opioid (p = 0.050), and was found satisfactory by a half of patients (n = 10, 50.0%). CONCLUSIONS: Our preliminary results suggest that CT may be considered for cancer patients with various types of CNP. Large studies are necessary to confirm our findings and ascertain which additional CNP show positive response to CT.

Impact of Type of Needle on Incidence of Intravascular Injection During Diagnostic Lumbar Medial Branch Block.

BACKGROUND AND OBJECTIVES: Intravascular (IV) injection of local anesthetics is a potential cause of false-negative results after lumbar medial branch nerve blockade (L-MBB) performed to diagnose facetogenic back pain. The aim of the present study was to identify the relationship between the needle type and the incidence of IV injection in patients undergoing L-MBB using fluoroscopy with digital subtraction imaging (DSI). METHODS: In this prospective randomized study, we compared the incidence of IV uptake of contrast medium using the Quincke needle and Whitacre needle under real-time DSI during L-MBB. Clinical and demographic factors associated with the occurrence of IV uptake were also investigated. RESULTS: In total, 126 patients were randomized into the Quincke needle group (n = 62) and Whitacre needle group (n = 64). Intravascular uptake of contrast medium was observed in 66 (9.8%) of 671 L-MBB procedures under DSI. The incidence of IV uptake was 13.9% (47/338) using the Quincke needle and 5.7% (19/333) using the Whitacre needle. In the multivariate generalized estimating equations analysis, use of a Quincke needle was related to positive IV injection at a 1.898-fold higher rate than was use of a Whitacre needle (95% confidence interval, 1.025-3.516) and a positive aspiration test predicted IV injection at a 21.735-fold higher rate (95% confidence interval, 11.996-52.258). CONCLUSIONS: Lumbar medial branch nerve blockade using the Quincke needle was associated with a 1.9-fold higher rate of IV injection than was L-MBB using the Whitacre needle under DSI. Although further study is needed to confirm the clinical efficacy, Whitacre needles can be considered to reduce the risk of IV injection during L-MBB.

Intrathecal Morphine Infusion Therapy in Management of Chronic Pain: Present and Future Implementation in Korea.

PURPOSE: Intrathecal morphine pump (ITMP) infusion therapy is efficient in managing malignant and nonmalignant chronic pain refractory to standard treatment. However, the high cost of an ITMP is the greatest barrier for starting a patient on ITMP infusion therapy. Using the revised Korean reimbursement guidelines, we investigated the cost effectiveness of ITMP infusion therapy and conducted a patient survey. MATERIALS AND METHODS: A retrospective chart review of 12 patients who underwent ITMP implantation was performed. Morphine dose escalation rates were calculated, and numeric rating scale (NRS) scores were compared before and after ITMP implantation. We surveyed patients who were already using an ITMP as well as those who were candidates for an ITMP. All survey data were collected through in-person interviews over 3 months. Data on the cost of medical treatment were collected and projected over time. RESULTS: The NRS score decreased during the follow-up period. The median morphine dose increased by 36.9% over the first year, and the median time required to reach a financial break-even point was 24.2 months. Patients were more satisfied with the efficacy of ITMP infusion therapy than with conventional therapy. The expected cost of ITMP implantation was KRW 4000000-5000000 in more than half of ITMP candidates scheduled to undergo implantation. CONCLUSION: The high cost of initiating ITMP infusion therapy is challenging; however, the present results may encourage more patients to consider ITMP therapy.

Epidural steroid injection in korean pain physicians: a national survey.

BACKGROUND: Epidural steroid injection (ESI) is one of the most common procedures for patients presenting low back pain and radiculopathy. However, there is no clear consensus on what constitutes appropriate steroid use for ESIs. To investigate optimal steroid injection methods for ESIs, surveys were sent to all academic pain centers and selected private practices in Korea via e-mail. METHODS: Among 173 pain centers which requested the public health insurance reimbursements for their ESIs and were enrolled in the Korean Pain Society, 122 completed questionnaires were returned, for a rate of 70.5%; also returned were surveys from 39 academic programs and 85 private practices with response rates of 83.0% and 65.9%, respectively. RESULTS: More than half (55%) of Korean pain physicians used dexamethasone for ESIs. The minimum interval of subsequent ESIs at the academic institutions (3.1 weeks) and the private practices (2.1 weeks) were statistically different (P = 0.01). CONCLUSIONS: Although there was a wide range of variation, there were no significant differences between the academic institutions and the private practices in terms of the types and single doses of steroids for ESIs, the annual dose of steroids, or the limitations of doses in the event of diabetes, with the exception of the minimum interval before the subsequent ESI.

Left ventricular outflow tract obstruction with systolic anterior motion of the mitral valve in patient with pericardial effusion caused by ascending aortic dissection -A case report-.

Left ventricular outflow tract (LVOT) obstruction with systolic anterior motion (SAM) of mitral valve is not only limited to patients with hypertrophic cardiomyopathy. A diagnosis of LVOT obstruction with SAM is important because conventional inotropic support may potentially aggravate hemodynamic deterioration. We present a case of LVOT obstruction with SAM in a patient who underwent an emergent surgery for ascending aortic dissection with pericardial effusion. The patient showed refractory hypotension after standard pharmacologic interventions during induction of anesthesia. Transesophageal echocardiography (TEE) revealed LVOT obstruction with SAM and it was managed appropriately under the guidance of TEE. Intraoperative TEE can play an important role in diagnosis and management of LVOT obstruction with SAM caused by pericardial effusion.

The influence of DNA polymorphism of multidrug resistant 1 (MDR1) on the effect of midazolam pretreatment in children.

BACKGROUND: Patients showed a different response following intravenous midazolam injection. Some children showed irritability or were not sedated by midazolam. We hypothesized that there may be genetic variations of the MDR1 gene, based on the response to midazolam. METHODS: One hundred and ninety-three pediatric patients were recruited in this study. Midazolam (0.1 mg/kg) was injected intravenously before surgery. Anxiety score (activity, vocalizations, emotional expressivity, state of apparent arousal) was checked before and 5 minutes after midazolam injection. In addition, other manifestations after midazolam injection were recorded. After anesthesia, 2 ml of blood was sampled. Children were genotyped MDR1. Haplotype was analyzed using the software package PHASE, version 2.0. RESULTS: The observed frequencies of MDR1 haplotype of TTT, TGC, CAC, CGC were 0.334, 0.205, 0.182 and 0.225, respectively. There was no significant correlation between the response of midazolam and the MDR1 haplotype of TTT, TGC, CAC or CGC (P = 0.98). CONCLUSIONS: Genotyping of MDR1 may not be related to the response of midazolam in children.

Damage to the cuff of EMG tube at endotracheal intubation by using a lightwand -A case report-.

Electromyogpraphic endotracheal tube (EMG tube) is a new device used to monitor recurrent laryngeal nerve integrity during thyroid surgery. The EMG tube has 2 pairs of electrodes on the surface of silicon-based tube reached to inner space of tube cuff. We experienced an unusual endotracheal tube-related problem from the distinct structural feature of the EMG tube. In this case, we intubated a patient who had difficult airway with the EMG tube using a lightwand. After successful endotracheal intubation, we could not expand the pilot balloon and ventilate the patient effectively. We removed the EMG tube and found that one of electrodes of the EMG tube is bended and made a right angle with the long axis of the tube, and perforated the tube cuff. So we report this case to make anesthesia providers aware that much more attention is needed to use EMG tube during endotracheal intubation.