Pei- Lin

Efficacy of Ultrafiltration in Removing Inflammatory Mediators During Pediatric Cardiac Operations

BACKGROUND Conventional and modified ultrafiltration was used in pediatric cardiac operations to reduce volume overload and total body water. The purpose of this study was to compare the efficacy of these techniques in removing inflammatory mediators during cardiopulmonary bypass. METHODS Fifty pediatric patients undergoing cardiac operations were randomized into a modified or conventional ultrafiltration group. Blood samples were obtained before and after ultrafiltration to assess the plasma concentrations of leukocyte elastase, tumor necrosis factor-alpha, interleukin-6, and interleukin-8. RESULTS Except for plasma concentrations of tumor necrosis factor-alpha in the modified ultrafiltration group, the plasma concentrations of all the mediators measured increased after ultrafiltration in both groups of patients. The volume of ultrafiltrate and the total amounts of tumor necrosis factor-alpha and interleukin-6 removed by ultrafiltration were significantly greater in the modified group. The concentrations of mediators in the ultrafiltrate and the ratio of ultrafiltrate to plasma concentrations of the mediators did not differ between the groups. Ultrafiltration was more efficient in removing tumor necrosis factor-alpha than the other mediators. CONCLUSIONS The efficacy in removing the inflammatory mediators generated during cardiopulmonary bypass did not differ between modified and conventional ultrafiltration.

Analgesic Effect of Lidocaine Patch 5% in the Treatment of Acute Herpes Zoster: A Double-Blind and Vehicle-Controlled Study

Background and Objectives: Although lidocaine patch 5% has been widely used for postherpetic neuralgia, its analgesic effect on the intense pain associated with acute herpes zoster has not been investigated because of its potential hazard to damaged skin. Methods: Forty‐six patients suffering from moderate to severe pain caused by acute herpes zoster infection (within 4 weeks of onset) were enrolled in a randomized, double‐blind, vehicle‐controlled, parallel study. Lidocaine patch 5% or vehicle patch were applied to the intact portion of the painful skin area without blisters at 12‐hour intervals twice a day for 2 consecutive days. Analgesic efficacy and side effect profiles were assessed before and 48 hours after patch application. Results: We found that both groups of patients experienced significant pain relief during rest and movement. Differences of mean reduction of pain intensity between the two groups were 14.7 (4.7‐24.8, P = 0.005) during rest and 10.4 (1.6‐19.3, P = 0.007) during movement, favoring the lidocaine patch. The lidocaine patch produced a greater percentage change in a patients global impression than the vehicle patch. The incidence and severity of adverse events were low with both treatments. Conclusions: This study demonstrates that lidocaine patch 5%, applied twice a day, could serve as a well tolerated and effective modality to relieve moderate to severe pain associated with acute herpes zoster presumably through its pharmacological action and physical barrier effect on sensitized skin.

Intravenous tenoxicam reduces uterine cramps after Cesarean delivery.

PurposePostpartum uterine contraction pain is a common phenomenon after Cesarean delivery. We investigated the effectiveness of tenoxicam in reducing uterine contraction pain.MethodsWe enrolled 120 consecutive non-breastfeeding women who were scheduled for elective Cesarean delivery. After the administration of spinal anesthesia with bupivacaine and intrathecal morphine 0.15 mg injection, the patients were randomly divided into two groups. Group I received placebo (normal saline) iv injection, and Group II received tenoxicam 40 mg iv injection after clamping the umbilical cord. Verbal analogue scale of wound pain and uterine contraction pain were recorded at two, four, eight, 16, and 24 hr after Cesarean delivery.ResultsThere was no significant difference in wound pain scores between the two groups (all scores ≤3). However, the tenoxicam group had significant lower uterine contraction pain scores and required less supplemental meperidine medication than did the placebo group (8.5% vs 41.4%,P < 0.05). The incidences of nausea or vomiting, pruritus, and bleeding were not significantly different between groups.ConclusionIntravenous tenoxicam 40 mg significantly reduced the intensity of uterine cramps in patients undergoing Cesarean delivery without increasing side effects.RésuméObjectifLa douleur des contractions utérines du postpartum est un phénomène fréquent après la césarienne. Nous avons vérifié l’efficacité du ténoxicam à réduire ces douleurs.MéthodeNous avons recruté 120 femmes qui devaient subir une césarienne non urgente et qui ne devaient pas allaiter leur bébé. Après la rachianesthésie avec de la bupivacaïne et une injection intrathécale de 0,15 mg de morphine, nous avons formé deux groupes. Les patientes du Groupe I ont reçu un placebo (soluté physiologique) iv et celles du Groupe II 40 mg iv de ténoxicam après le clampage du cordon ombilical. L’échelle verbale analogique a servi à enregistrer la douleur postopératoire liée à l’incision et aux contractions utérines à deux, quatre, huit, 16 et 24 h.RésultatsLes scores de douleurs liées à l’incision n’ont pas différé d’un groupe à l’autre (tous les scores ont été ≤ 3). Par ailleurs, dans le groupe ténoxicam, les scores liées aux contractions utérines ont été plus bas et les demandes d’analgésie supplémentaire avec mépéridine moins importantes que dans le groupe placebo (8,5 % vs 41,4%, P < 0,05). Nausées, vomissements, prurit ou saignements n’ont pas présenté de différence intergroupe significative.ConclusionUne dose intraveineuse de 40 mg de ténoxicam a réduit significativement l’intensité des crampes utérines sans causer d’effets secondaires à la suite d’une césarienne.

Effect of ropivacaine on endothelium-dependent phenylephrine-induced contraction in guinea pig aorta

Background:  Previous studies have shown that ropivacaine has biphasic vascular effects, causing vasoconstriction at low concentrations and vasorelaxation at high concentrations. This study was designed to examine the role of the endothelium during accidental intravascular absorption of ropivacaine, and to elucidate the mechanisms responsible.

Lack of intravenous lidocaine effects on HRV changes of tracheal intubation during induction of general anesthesia.

BACKGROUND Intravenous lidocaine has been widely used for suppressing the autonomic activation from tracheal intubation during induction of general anesthesia. Conventionally, researches of its effectiveness through assessment of heart rate and blood pressure changes obtained by common clinical methods result in the conclusions deduced of much controversy. Heart rate variability is a noninvasive measurement of autonomic regulation and is suitable for the study of this subject. METHODS 36 ASA class I-II patients undergoing general anesthesia were divided into 3 groups. Besides induction agents, intravenous lidocaine was given 5 min before tracheal intubation in group A, 3 min before intubation in group B and nothing in group C. HRV spectral powers were measured at awake state, anesthetized state before tracheal intubation and anesthetized state after tracheal intubation by time frequency spectral analysis method and comparison was made between the three groups. RESULTS The HRV spectral power in high frequency (HF) and mid-frequency (MF) power bands and their ratios (MF/HF) were not significantly different among the 3 groups during the 3 observation periods. CONCLUSIONS There was no evidence to indicate the effectiveness of intravenous lidocaine on the autonomic regulation during tracheal intubation under the influence of induction agents used in general anesthesia.

Ecstasy and methamphetamine elicit action potential bursts via different mechanisms in a central snail neuron.

This study sought to determine the effects of (+) methamphetamine (METH) and its ring-substituted analog (+/-)3,4-methylenedioxymethamphetamine (MDMA; ecstasy) on electrophysiological behavior and their relationships to second messenger systems in an identifiable RP4 neuron of the African snail, Achatina fulica Ferussac. Extracellular application of MDMA at 1mM and METH at 3mM elicited action potential bursts that were not blocked after immersing the neurons in Ca(2+)-free solution. Notably, MDMA- (1mM) elicited action potential bursts were blocked by pretreatment with the protein kinase C (PKC) inhibitors chelerythrine (20 microM) and Ro 31-8220 (20 microM), but not by the PKA inhibitors KT-5720 (10 microM) and H89 (10 microM). The PKC activator phorbol 12,13-dibutyrate (PDBu; 3 microM), but not the PKA activator forskolin (50 microM), facilitated the induction of bursts elicited by MDMA at a lower concentration (0.3mM). In contrast, METH- (3mM) elicited action potential bursts were blocked by pretreatment with KT-5720 (10 microM) and H89 (10 microM), but not by chelerythrine (20 microM) and Ro 31-8220 (20 microM). Forskolin (50 microM), but not PDBu (3 microM) facilitated the induction of bursts elicited by METH at a lower concentration (1mM). Tetraethylammonium chloride (TEA), a blocker of the delayed rectifying K(+) current (I(KD)), did not elicit bursts at a concentration of 5mM but did facilitate the induction of action potential bursts elicited by both METH and MDMA. Voltage clamp studies revealed that both METH and MDMA decreased the TEA-sensitive I(KD) of the RP4 neuron. Forskolin (50 microM) or dibutyryl cAMP (1mM), a membrane-permeable cAMP analog, alone did not elicit action potential bursts. However, co-administration with forskolin (50 microM) and TEA (5mM) or co-administration with dibutyryl cAMP (1mM) and TEA (50mM) elicited action potential bursts in the presence of the PKC inhibitor chelerythrine (20 microM). Similarly, PDBu (10 microM) or phorbol 12-myristate 13-acetate (PMA; 3 microM) alone did not elicit action potential bursts. However, co-administration with PDBu (10 microM) and TEA (5mM) or co-administration with PMA (3 microM) and TEA (5mM) elicited action potential bursts in the presence of the PKA inhibitor KT-5720 (10 microM). These data suggest that action potential bursts in the RP4 neuron were not due to Ca(2+)-dependent synaptic effects. Rather, action potential bursts may be elicited through (1) combined activation of the cAMP-PKA signaling pathway and inhibition of the I(KD) and (2) combined activation of PKC and inhibition of the I(KD).

Restricted Motion of a Mechanical Mitral Valve

A 59-year-old man with symptomatic severe mitral regurgitation (MR) was scheduled for mitral valve repair. Pre–cardiopulmonary bypass (CPB) transesophageal echocardiography (TEE) revealed severe MR with prolapse of the P2 and P3 segments (middle and posterior segments of the posterior leaflet) and posterior leaflet chordae rupture. P2/P3 plication with a 29-mm open Carpentier-Edwards Physio ring (Edwards Lifesciences, Irvine, CA) was performed during the first CPB period (2 hours 55 minutes). Because of persistent residual transvalvular regurgitation, the surgeon replaced the mitral valve with a 31-mm St. Jude bileaflet mechanical valve (St. Jude Medical, St. Paul, MN). To facilitate long-term ventricular remodeling, the surgeon preserved the posterior leaflet subvalvular apparatus and excised the anterior mitral leaflet. Examination of the prosthesis while still on CPB revealed small characteristic transvalvular regurgitant washing jets. However, after separation from the second period of CPB (1 hour 48 minutes), color flow Doppler examination revealed 2 transvalvular regurgitant jets (jet area 40% of atrial area, MR estimated as 4 ) (Fig. 1) (Video 1, see Supplemental Digital Content 1, http://links.lww.com/AA/A111) originating within the sewing ring without evidence of paravalvular leaks. A circular mass 10 8 mm was noted by 2-dimensional examination 0.5 cm below the annular ring (Fig. 2A). The mass was stuck between the posterior mechanical leaflet and ring, resulting in incomplete closure of the posterior mechanical leaflet during systole (Fig. 2B). Thus, a third period of CPB was instituted during which visual inspection of the mitral prosthesis revealed that the remnant of the native posterior leaflet was entrapped between the sewing ring and the prosthetic leaflet. After removing the prosthesis, total resection of the redundant posterior mitral leaflet (mainly P3 portion) was performed, followed by reimplantation of the prosthesis. The patient was weaned off CPB (1 hour 28 minutes) with dopamine and epinephrine support and subsequent TEE examination revealed competence of the mechanical valve without pathologic regurgitant jets. The patient was tracheally extubated the next day, but the postoperative course was complicated 1 week later by postoperative ischemic stroke, presenting as left hemiplegia. Sparing the subvalvular apparatus during mitral valve replacement is frequently performed. Its benefits include reduced risk of left ventricular rupture, restoration of left ventricular function by maintenance of annulo-ventricular continuity, and improved 1and 5-year survival. However, sparing the subvalvular apparatus may result in complications, such as inhibition of the normal mechanical opening or closing caused by obstruction by native mitral tissue. Bolliger et al. have reported immobilization of a valve leaflet in the open position after mitral valve replacement surgery, although intraoperative TEE failed to identify any structure responsible for obstructing leaflet motion. Agostini et al. described a patient with paroxysmal congestive heart failure caused by intermittent entrapment of the subvalvular apparatus inside the prosthesis, preventing complete valve closure 4 years after mitral valve replacement with preservation of the subvalvular apparatus. Other perioperative possible causes for malfunction of a mitral prosthesis are a misplaced suture interfering with leaflet motion, debris within the hinges entrapping the leaflet in a fixed position causing intermittent coaptation, and dehiscence of the prosthesis usually presenting as a rocking motion. Before separation from CPB, the echocardiographer should perform an abbreviated TEE examination to assess the need for optimizing ventricular function, to guide the deairing process, and to make an initial assessment of the mitral prosthesis. After separation from CPB, overall cardiac performance can be assessed by a comprehensive examination with a thorough evaluation of the prosthesis to determine the success of the surgery. Stepwise TEE examination for evaluating a mitral prosthesis should include the following: confirm proper leaflet motion and valve seating in 4 midesophageal views (4C, mitral commissural, 2C, and long axis) and/or in the transgastric views with 2-dimensional as well as color flow Doppler echocardiography, to identify any residual intracardiac densities that may interfere with leaflet motion in both the midesophageal and deep transgastric views, to confirm normal blood flow patterns and the absence of pathologic transvalvular and paravalvular regurgitation by color flow Doppler, and to estimate hemodynamic variables by continuous wave Doppler (Table 1). However, the underfilled chambers and partial contraction of the atrial and ventricular chambers may mask abnormalities of the mitral prosthesis when evaluated before weaning from CPB and result in TEE findings different from those after separation from CPB. In our case, the posterior leaflet remnant did not interfere with normal systolic prosthetic leaflet motion while on CPB. After weaning from CPB, the restored left ventricular volume and enhanced contractility due to inotropic support caused elevation of the native mitral tissue basally and its entrapment between the sewing ring and the posterior mechanical leaflet, resulting in reduced motion of the mechanical leaflet and severe MR. TEE has important roles during and after separation from CPB for valve replacement surgery. From the Department of Anesthesiology, National Taiwan University Hospital, Taipei, Taiwan, Republic of China.

Neurotoxicity of a Novel Local Anesthetic Agent, Ropivacaine: The Possible Roles of Bursts of Potential and Cytoplasmic Second Messenger

BACKGROUND/PURPOSE Ropivacaine has been shown to induce convulsion following overdose or accidental intravenous injection, but the mechanisms are poorly understood. Using an identifiable central neuron from giant African snail, the authors studied the mechanism of ropivacaine-elicited bursts of potential and explored the possible mechanisms of ropivacaine-induced neurotoxicity. METHODS Ropivacaine action on a central neuron (RP4) of the giant African snail (Achatina fulica Ferussac) was recorded by conventional electrophysiologic technique. Interactions between ropivacaine and prazosin, propranolol, atropine, d-tubocurarine, calcium-free solution, H89, U73,122, neomycin, high-magnesium solution, and chelerythrine were also observed. RESULTS The RP4 neuron showed spontaneous firing of action potentials. Extracellular application of ropivacaine (900 microM) reversibly elicited bursts of potential in the RP4 neuron. The bursts of potential elicited by ropivacaine were not blocked after administration of: (1) prazosin, propranolol, atropine, d-tubocurarine; (2) calcium-free solution; and (3) pretreatment with H89 or chelerythrine. The bursts of potential elicited by ropivacaine were blocked by pretreatment with U73122 (30 microM) or by adding neomycin (3.5 mM) or high-magnesium solution (30 mM). CONCLUSION Ropivacaine reversibly elicited bursts of potential in the central snail neuron. The ropivacaine-elicited bursts of potential were associated with phospholipase C activity in the RP4 snail neuron. Our results suggest that ropivacaine-induced neurotoxicity is highly associated with phospholipase C activity and phospholipase C inhibitor may offer a novel therapeutic approach for managing local anesthetic-induced convulsion or other transient neurologic toxicity.

Effects of a New Isoquinolinone Derivative on Induction of Action Potential Bursts in Central Snail Neuron

The effects of 7-bromo-1,4-dihydro-2-phenyl-4,4-bis(4-pyridinylmethyl)2H-isoquinolin-3-one dihydrochloride (BDPBI) on induction of action potential bursts were studied pharmacologically on the RP4 central neuron of the giant African snail (Achatina fulica Ferussac). The effects of m-3M3FBS, a phospholipase activator and HTMT, a histamine (H1) receptor agonist, on the neuron were also tested. The RP4 neuron showed spontaneous firing of action potential. Extracellular application of BDPBI (150 µmol/l) reversibly elicited bursts of potential (BoP) on the neuron. m-3M3FBS and HTMT also elicited BoP on the RP4 neuron. The BoP elicited by BDPBI were blocked by U73122 (6 µmol/l), a compound commonly used as a phospholipase C (PLC) inhibitor. Neomycin (3.5 mmol/l), a high-magnesium solution (30 mmol/l), replacing the physiological sodium ion with lithium ion or adding diphenhydramine, chloropheniramine decreased the BoP elicited by BDPBI. The BoP elicited by BDPBI were not inhibited after administration with (1) prazosin, propranolol, atropine, d-tubocurarine, hexamethonium, haloperidol, cimetidine, (2) calcium-free solution, (3) high-potassium (12 mmol/l) solution, and (4) pretreatment with KT-5720. The BoP elicited by HTMT was not inhibited after administration of diphenhydramine or chloropheniramine. Voltage-clamped studies revealed that BDPBI decreased the amplitudes of calcium and steady-state outward currents while it did not alter the amplitude of the fast inward current. No negative slope relationship of the steady-state current voltage relationship was found in BDPBI-treated neurons. It is concluded that BDPBI reversibly elicited BoP in the central snail neuron. The effect was not due to (1) the extracellular calcium ion fluxes, or (2) the activation of cholinergic, adrenergic or histamine receptors. The BDPBI-elicited BoP were dependent on the phospholipase activity in the neuron.

Effects of rolipram on induction of action potential bursts in central snail neurons

Effects of rolipram, a selective inhibitor of phosphodiesterases (PDE) IV, on induction of action potential bursts were studied pharmacologically on the RP4 central neuron of the giant African snail (Achatina fulica Ferussac). Oscillations of membrane potential bursts were elicited by rolipram and forskolin. The bursts of potential elicited by rolipram were not inhibited after administration with (a) calcium-free solution, (b) high-magnesium solution (30 mM) or (c) U73122. However, the bursts of potential elicited by rolipram were inhibited by pretreatment with KT-5720 (10 microM). Voltage-clamp studies revealed that rolipram decreased the total inward current and steady-state outward currents of the RP4 neuron. The negative slope resistance (NSR) was not detectable in control or rolipram treated RP4 neurons. TEA elicited action potential bursts and an NSR at membrane potential between -50 mV and -30 mV. It is suggested that the bursts of potential elicited by rolipram were not due to (1) synaptic effects of neurotransmitters; (2) NSR of steady-state I-V curve; (3) phospholipase activity of the neuron. The rolipram-elicited bursts of potential were dependent on the phosphodiesterases inhibitory activity and the cAMP signaling pathway in the neuron.