Protamine sulfate is the antidote for heparin, but in excess it exerts weak anticoagulation.

We evaluated the effects of increasing protamine concentrations (0 to 24 µg/mL) on prothrombin time and diluted Russell's viper venom time measurements on thrombin generation in platelet-poor and platelet-rich plasma after activation by tissue factor or actin, and on thromboelastometry in platelet-poor plasma and whole blood from 6 healthy volunteers. The reversibility of excess protamine (24 µg/mL) by recombinant factor VIIa or factor VIII/von Willebrand factor concentrate was also tested.

Protamine prolonged prothrombin time and Russell's viper venom time, concentration dependently. Protamine also increased lag time and decreased peak of thrombin generation in platelet-poor plasma after tissue factor and actin activation. In platelet-rich plasma with platelets at 50 to 200 x 10³/µL, protamine (24 µg/mL) prolonged the lag time, but had no effect on peak thrombin generation. The addition of factor VIII/von Willebrand factor (1.5–3.0 U/mL) to platelet-poor plasma with protamine (24 µg/mL) decreased lag time and increased peak thrombin generation with actin activation. A therapeutic concentration of recombinant factor VIIa (60 nM) only affected the lag time of thrombin generation triggered with actin. In agreement, protamine increased coagulation time evaluated by thromboelastometry significantly more in platelet-poor plasma than in whole blood.

We demonstrated that protamine affects the propagation of thrombin generation, which is partially reversed by platelets or increased factor VIII/von Willebrand factor concentrations. The present data suggest that excess protamine might potentially increase bleeding in the case of severe thrombocytopenia or low factor VIII.

There is a lack of clinical registries to document efficacy and safety of ultrasound-guided regional anesthesia. Interscalene blocks are effective for shoulder arthroscopy, and ultrasound guidance may reduce risk. Furthermore, ultrasound-guided supraclavicular block is a novel approach for shoulder anesthesia that may have less risk for neurological symptoms than interscalene block.

One thousand one hundred sixty-nine patients undergoing ultrasound-guided regional anesthesia for ambulatory shoulder arthroscopy were enrolled in our prospective registry. Standardized perioperative data were collected including a preoperative neurological screening tool. Either interscalene or supraclavicular block was performed at the discretion of the clinical team. Standardized follow-up was performed in the postanesthesia care unit and at 1 week. Postoperative neurological symptoms (PONS) were assessed at the 1-week follow-up with the same screening tool by a blinded neurologist.

Ultrasound-guided interscalene (n = 515) and supraclavicular (n = 654) blocks had excellent anesthetic success (99.8%; 95% confidence interval [CI], 99.4%–99.9%) with 0% (95% CI, 0%–0.3%) incidence of vascular puncture or intravascular injection. The incidence of hoarseness in the postanesthesia care unit was significantly less with supraclavicular (22% with 95% CI, 19%–26%) than interscalene block (31% with 95% CI, 27%–35%). The incidence of dyspnea was similar (7% for supraclavicular vs 10% with interscalene). No patient had a clinically apparent pneumothorax. The incidence of PONS was very low (0.4% with 95% CI, 0.1%–1%), and there was a 0% (95% CI, 0%–0.3%) incidence of permanent nerve injury.

Ultrasound-guided interscalene and supraclavicular blocks are effective and safe for shoulder arthroscopy. Temporary and permanent PONS is uncommon.

In pharmacokinetic–pharmacodynamic modeling studies, venous plasma samples are sometimes used to derive pharmacodynamic model parameters. In the current study the extent of arteriovenous concentration differences of morphine-6-glucuronide (M6G) was quantified. We used simulation studies to estimate possible biases in pharmacodynamic model parameters when linking venous versus arterial concentrations to effect.

Seventeen healthy volunteers received an IV 90-second infusion of 0.3 mg/kg morphine-6-glucuronide (M6G). Arterial and venous blood samples, from the radial artery and cubital vein, respectively, were obtained. An extended pharmacokinetic model was constructed linking arterial and venous compartments. The extent of bias in pharmacodynamic model parameter estimates was explored in simulation studies with NONMEM, simulating M6G effect using first-order effect-compartment–inhibitory sigmoid E_MAX models. M6G effect was simulated at various values for the arterial blood-effect-site equilibration half-lifes (t1/2k_E0), ranging from 5 to 240 minutes.

Arteriovenous concentration differences were apparent, with higher arterial plasma concentrations just after infusion, whereas at later times (>60 minutes) venous M6G concentrations exceeded arterial concentrations. The extended pharmacokinetic model adequately described the data and consisted of 3 arterial compartments, 1 central venous compartment, and 1 peripheral venous compartment. The simulation studies revealed large biases in model parameters derived from venous concentration data. The biases were dependent on the value of t1/2k_E0. Assuming that the true values of M6G t1/2k_E0 range from 120 to 240 minutes (depending on the end point measured), we would have underestimated t1/2k_E0 by 30%, whereas the potency parameter would have been overestimated by about 40%, when using venous plasma samples.

Because of large arteriovenous differences in M6G plasma, concentration biases in pharmacodynamic model parameters will occur when linking venous concentration to effect, using a traditional effect-compartment model.

Gabapentin is a structural analog of -aminobutyric acid, one of the inhibitory neurotransmitters of the mammalian central nervous system. It is increasingly being used preemptively to control postoperative pain. Therefore, its interaction with inhaled anesthetics is of clinical interest. In this study, we examined the effects of gabapentin on the minimum alveolar concentration (MAC) of isoflurane in cats. We hypothesized that gabapentin would decrease the MAC of isoflurane in a dose-dependent manner.

Six cats were included in the study. Gabapentin was administered IV to achieve target plasma concentrations between 0 and 16 µg/mL and the MAC of isoflurane was determined at each gabapentin concentration. Gabapentin concentrations were quantitated by liquid chromatography–mass spectrometry analysis of extracted plasma samples. MAC values at the different gabapentin plasma concentrations were analyzed by a repeated-measures analysis of variance using the Huynh-Feldt correction for violation of the sphericity assumption.

Actual gabapentin concentrations were 0 ± 0, 1.18 ± 0.23, 2.25 ± 0.23, 4.96 ± 1.19, 10.63 ± 1.37, and 19.69 ± 3.97 µg/mL for the target concentrations of 0, 1, 2, 4, 8, and 16 µg/mL, respectively. The MAC of isoflurane in this study was 2.10%± 0.13%, 2.10% ± 0.14%, 2.13% ± 0.12%, 2.06% ± 0.11%, 2.11% ± 0.15%, and 2.09% ± 0.25% at target plasma concentrations of 0, 1, 2, 4, 8, and 16 µg/mL, respectively.

We conclude that gabapentin did not have a detectable effect on the MAC of isoflurane in cats.

Droperidol is a highly potent butyrophenone used for the therapy of postoperative nausea and vomiting. Its cardiac safety in cardiovascular-healthy patients and those with long QT (LQT) syndrome is a matter of debate. In this study, we investigated whether droperidol has subtype-specific effects in cellular and computational models of LQT syndrome.

Left ventricular cardiac myocytes were isolated from adult guinea pig hearts. LQT1-like behavior was pharmacologically induced by chromanol 293B (10 µmol/L) and LQT2-like states by E4031 (10 µmol/L). Computational analysis was performed using the Luo-Rudy dynamic model. Data are given as mean ± SEM.

In control myocytes, droperidol lengthened action potentials in a concentration-dependent manner with a maximal prolongation of 37%± 13% (n = 4) at a concentration of 0.6 µmol/L. In LQT1-like myocytes, droperidol (0.6 µmol/L) further prolonged action potentials by 31% ± 6% (n = 6) but shortened action potentials of LQT2-like myocytes by 11% ± 2% (n = 8). Computational modeling supported the concept that droperidol, in addition to the rapid component of the delayed K⁺ current, blocks depolarizing targets, such as the L-type Ca²⁺ current, the Na⁺-Ca²⁺ exchanger, and the Na⁺-K⁺ adenosine triphosphatase.

Droperidol has more detrimental effects on cardiac repolarization of LQT1-like than of LQT2-like myocytes suggesting subtype-specific cardiotoxic effects in patients with LQT syndrome. The subtype specificity of droperidol seems to be caused by a complex interaction of droperidol with several different molecular targets. This interaction deserves further investigation to establish the feasibility of a subtype-directed approach in the perioperative management of patients with LQT syndrome.

Anterior retraction of the tongue is used to enhance upper airway patency during pediatric fiberoptic intubation. This can be achieved by the use of Magill forceps as a tongue retractor, but lingual grip can become unsteady and traumatic. Our objective was to modify this instrument using computer-aided engineering for the purpose of stable tongue retraction.

We analyzed the geometry and mechanical properties of standard Magill forceps with a combination of analytical and empirical methods. This design was captured using computer-aided design techniques to obtain a 3-dimensional model allowing further geometric refinements and mathematical testing for rapid prototyping.

On the basis of our experimental findings we adjusted the design constraints to optimize the device for tongue retraction. Stereolithography prototyping was used to create a partially functional plastic model to further assess the functional and ergonomic effectiveness of the design changes. To reduce pressure on the tongue by regular Magill forceps, we incorporated (1) a larger diameter tip for better lingual tissue pressure profile, (2) a ratchet to stabilize such pressure, and (3) a soft molded tip with roughened surface to improve grip.

Computer-aided engineering can be used to redesign and prototype a popular instrument used in airway management. On a computational model, our modified Magill forceps demonstrated stable retraction forces, while maintaining the original geometry and versatility. Its application in humans and utility during pediatric fiberoptic intubation are yet to be studied.

Patient monitoring displays are designed to improve patient safety, and yet little is known about how anesthesiologists interact with these displays. Previous studies of clinician behavior used an observer in the operating room, which may have altered behavior. We describe a covert observation technique to determine how often and for how long anesthesiologists actually look at the monitoring display during different segments of the maintenance phase of anesthesia, and to determine whether this changed with more than 1 anesthesia provider or during concomitant activities such as reading.

Five staff anesthesiologists, 2 anesthesia fellows, 3 anesthesia residents, and 2 medical students were covertly videotaped across 10 dual anesthesia provider cases and 10 solo cases. Videotapes were later segmented (5 minutes postinduction [early maintenance], mid-maintenance, and immediately before the drapes came down [late maintenance]) and coded for looking behavior at the patient monitor, anesthesia chart, and other reading material.

Anesthesiologists looked at the monitor in 1- to 2-second glances, performed frequently throughout the 3 segments of maintenance anesthesia. Overall, the patient monitor was looked at only 5

of the analyzed time, which is less than has previously been reported. Monitoring behavior was constant across the segments of maintenance anesthesia and was not significantly affected by the number of anesthesia providers or role (trainee vs. senior). In contrast, charting behavior and other reading material viewing changed significantly over the analyzed segments of maintenance anesthesia.

The presence of "at-a-glance monitoring" has implications for the design of patient monitoring displays. Displays should be developed to optimize the information obtained from brief glances at the monitor.

The common practice of maintaining central venous pressure (CVP) below 5 mm Hg to reduce blood loss during hepatic resection increases the risk of venous air embolism (VAE). We initiated this study after observing that the anteroposterior (AP) diameter of the liver can be much larger than 7 cm, which is the approximate hydrostatic pressure corresponding to a CVP of 5 mm Hg (1 mm Hg = 1.36 cm H₂O). The purpose of this study was to characterize the liver AP diameter and thereby describe how this might affect the placement of the CVP transducer to balance the risks of bleeding and VAE.

We measured the AP liver diameter and its distance from other anatomic sites using consecutive archived chest tomograms with IV contrast from 100 adults.

The results of our study demonstrate a large interindividual range in AP liver dimensions (17.9 ± 2.8 cm, range = 12.0–28.5 cm) and standardized anatomic landmarks relative to the portal triad.

The significant variability in AP liver diameter, along with the variability in the liver surgical site, suggests that we rethink the zero reference point for the CVP transducer during hepatic surgeries. By considering the actual hepatic venous pressure itself, rather than the CVP, we can minimize the risks of VAE and hemorrhage. Two methods for zeroing the reference transducer are suggested.

We sought to determine the impact of a rapid response system on cardiac arrest rates and mortality in a United States veteran population.

We describe a prospective analysis of cardiac arrests in 9 months before and 27 months after institution of a rapid response system, and retrospective analysis of mortality 3.5 years before the intervention and 27 months after the intervention. The study included all inpatients from a university-affiliated United States Veterans Affairs Medical Center, before and after implementation of a rapid response system, including an educational program, patient calling criteria, and a physician-led medical emergency team. Primary end points were hospital-wide cardiac arrests and mortality rates normalized to hospital discharges. Comparisons of event rates between various time points during the implementation process were made by analysis of variance.

Three hundred seventy-eight calls were made to the medical emergency team in the time period studied. Compared with preintervention time points, cardiac arrests were reduced by 57%, amounting to a reduction of 5.6 cardiac arrests per 1000 hospital discharges (P < 0.01). Mortality was reduced during the intervention, but this was attributable to a natural decrease occurring over all phases of the study.

A significant reduction in the rate of cardiac arrests was realized with this intervention, as well as a trend toward lower mortality. We estimate that 51 arrests were prevented in the timeframe studied. Our results suggest that further reductions in morbidity can be realized by expansion of rapid response systems throughout the Veterans Affairs network.

Chest radiography has been reported to have low diagnostic accuracy in critically ill intensive care unit (ICU) patients, and chest computed tomography (CT) scans require patients to be transported out of the ICU, putting them at risk of adverse events. In this study we assessed the efficacy of routine bedside lung ultrasound (LUS) in the evaluation of pleural effusions (PE) in the ICU.

Three hundred seventy-six patients admitted to the ICU for major trauma (46.3%), medical pathology (41.5%), and postsurgical complications (12.2%) (May 2008 to April 2009) were included in this study. Patients were placed into either the control group (group C) or the study group (group S), on the basis of the introduction of routine LUS performed by a single group of intensivists in 1 tertiary care ICU. To reduce provider bias, the physicians conducting the LUS were not aware of the study. Collected data included patient demographics, clinical course, and number of chest radiographs and CT scans performed. As a secondary goal, we assessed the reliability of Balik's formula in PE estimation.

No significant differences were found between the 2 groups with regard to their demographics and ICU clinical course. Group S had a significant reduction in the total number of chest radiographs obtained (–26%; P < 0.001) and CT scans (–47%; P < 0.001) in comparison with the comparison group C. A 6-month follow-up analysis of the ICU LUS protocol revealed a time-dependent decrease in the number of radiological examinations requested for patients with PE. Lastly, PE volume estimation using the LUS and Balik's formula correlates well with the effective volume drained (r = 0.65; P < 0.0001).

Routine use of LUS in the ICU setting can be associated with a reduction of the number of chest radiographs and CT scans performed.

Supraglottic jet ventilation (JV_S) with injectors above airway stenoses may result in inadvertent high lung pressures. We designed this study to investigate intrinsic positive end-expiratory pressure (PEEP_i) during jet ventilation via a distant injector in a model of dynamic upper airway obstruction.

Respiratory pressure-time curves were recorded during JV_S in a tracheal lung model using a pig's trachea and an embolectomy catheter's air-filled balloon to simulate 60

and 80% airway obstruction. JV_S was performed at various jet frequencies (F_jet 30 min^–1, 60 min^–1, and 100 min^–1) and driving pressures (1 bar and 2 bar).

JV_S was associated with generation of PEEP_i, which depended on driving pressure, the degree of obstruction, and on ventilatory frequency.

In the presence of a dynamic upper airway obstruction, JV_S via a distant injector may result in PEEP_i, which cannot be detected when airway pressure is measured in front of the obstruction.

We investigated whether preoperative positional arterial blood pressure change predicted hypotension and ephedrine requirement during spinal anesthesia for cesarean delivery.

Arterial blood pressure was measured in 66 women undergoing cesarean delivery in the supine and the right lateral positions. Positional blood pressure change was defined as the difference between mean blood pressure in the right lateral and supine positions. Hypotension (<80% baseline) was recorded, and severe hypotension (<70% baseline) was treated with ephedrine.

The mean (range) positional blood pressure change was 11 (3–29) mm Hg, and the incidence of hypotension was 41%. Positional blood pressure change and heart rate correlated with hypotension (P < 0.001 for both) and ephedrine requirement (P = 0.004). Positional blood pressure change in those who developed hypotension was higher than for those without hypotension (mean (SD), 17 (6) vs. 7 (2) mm Hg, P < 0.001).

A preoperative increase in blood pressure after position change may be a good variable to predict hypotension during spinal anesthesia for cesarean delivery.

Several studies suggest that many parents and research participants have poor understanding of the elements of consent, particularly the risks and benefits. However, some data suggest that the format and framing of research risks and benefits may be an important determinant of subject understanding. We examined the effect of tabular and graphical presentation of risks and benefits on parents' understanding of a research study.

Parents of children scheduled to undergo an elective surgical procedure (n = 408) were randomized to receive information about the risks and benefits of a sham study of postoperative pain control using text, tables, or pictographs and then completed a questionnaire to examine their gist (essential) and verbatim (actual) understanding of the information. Parent demographics were recorded and their literacy and numeracy skills measured.

Parents randomized to receive information using tables or pictographs had significantly (P < 0.025) greater gist and verbatim understanding than did parents who received the information using standard text. Tables and pictographs were also superior to text in promoting understanding among parents with low numeracy and literacy skills.

Many parents and patients have difficulty in assimilating and interpreting risk/benefit information for both research and treatment. This is due, in part, to the manner in which risks and benefits are communicated and to the literacy and numeracy abilities of the individual. The results of this study suggest a simple and practical method for enhancing understanding of risk/benefit statistics for parents with varying numeracy and literacy skills.

Percutaneous cannulation of the femoral vein, in the pediatric age group, can be technically challenging, especially when performed by residents in training. We examined whether the use of real-time ultrasound guidance is superior to a landmark technique for femoral vein catheterization in children undergoing heart surgery.

Patients were prospectively randomized into 2 groups. In group LM, the femoral vein was cannulated using the traditional method of palpation of arterial pulse. In group US, cannulation was guided by real-time scanning with an ultrasound probe. The time to complete cannulation (primary outcome), success rate, number of needle passes, number of successful cannulations on first needle pass, and incidence of complications were compared between the 2 groups.

Forty-eight pediatric patients were studied. The time to complete cannulation was significantly shorter (155 [46–690] vs 370 [45–1620] seconds; P = 0.02) in group US versus group LM. The success rate was similar in both groups (95.8%). The number of needle passes was smaller (1 [1–8] vs 3 [1–21]; P = 0.001) and the number of successful cannulations on first needle pass higher (18 vs 6; P = 0.001) in group US compared with group LM. The incidence of femoral artery puncture was comparable between the 2 groups.

Ultrasound-guided cannulation of the femoral vein, in pediatric patients, when performed by senior anesthesia residents, is superior to the landmark technique in terms of speed and number of needle passes, with remarkable improvement in first attempt success.

The occurrence of perioperative seizures in patients with a preexisting seizure disorder is unclear. There are several factors unique to the perioperative period that may increase a patient's risk of perioperative seizures, including medications administered, timing of medication administration, missed doses of antiepileptic medications, and sleep deprivation. We designed this retrospective chart review to evaluate the frequency of perioperative seizures in patients with a preexisting seizure disorder.

We retrospectively reviewed the medical records of all patients with a documented history of a seizure disorder who received an anesthetic between January 1, 2002 and December 31, 2007. Patients excluded from this study include those who had an outpatient procedure or intracranial procedure, ASA classification of V, pregnant women, and patients younger than 2 years of age. The first hospital admission of at least 24 hours during which an anesthetic was provided was identified for each patient. Patient demographics, character of the seizure disorder, details of the surgical procedure, and clinically apparent seizure activity in the perioperative period (within 3 days after the anesthetic) were recorded.

During the 6-year study period, 641 patients with a documented seizure disorder were admitted for at least 24 hours after an anesthetic. Twenty-two patients experienced perioperative seizure activity for an overall frequency of 3.4%(95% confidence interval, 2.2%–5.2%). The frequency of preoperative seizures (P < 0.001) and the timing of the most recent seizure (P < 0.001) were both found to be significantly related to the likelihood of experiencing a perioperative seizure. As the number of antiepileptic medications increased, so did the frequency of perioperative seizures (P < 0.001). Neither the type of surgery nor the type of anesthetic (general anesthesia, regional anesthesia, or monitored anesthesia care) affected the frequency of perioperative seizures in this patient population.

We conclude that the majority of perioperative seizures in patients with a preexisting seizure disorder are likely related to the patient's underlying condition. The frequency of seizures is not influenced by the type of anesthesia or procedure. Because patients with frequent seizures at baseline are likely to experience a seizure in the perioperative period, it is essential to be prepared to treat seizure activity regardless of the surgical procedure or anesthetic technique.

Case cancellations on the day of surgery reduce operating room (OR) and anesthesia group productivity. One strategy to reduce the impact of case cancellations on productivity is to assign high-risk cases to start last in the OR workday. To evaluate the utility of this intervention, we used a database of canceled cases to model the process of identifying high-risk cases and resequencing them to be the surgeons' last cases of the day.

Descriptive information was prospectively collected on 1 year of canceled cases. A comparison group of completed cases served as controls. Predictors of case cancellation were identified and used to calculate the number of cases that would require resequencing for 1 cancellation to occur at the end of the day. The proportion of total OR hours relevant to each predictor was assessed. To assess the desirability of this strategy, surgeons were surveyed regarding their scheduling preferences for patients at high risk for cancellation.

During the study period, 946 of 12,253 cases were canceled. Strong predictors of cancellation included percentage of missed clinic appointments (number of cases requiring resequencing = 5.27) and insurance status (number of cases requiring resequencing = 8.87 for Medicaid). The predictor accounting for the most scheduled time was residence in Chicago (5.1% of total hours). No predictor both required the resequencing of 5 or fewer cases to prevent 1 cancellation in the middle of the day and accounted for >4% of scheduled time. Survey results demonstrated that in addition to cancellation probability, factors such as case complexity also influenced surgeons' sequencing preferences.

Highly sensitive predictors of case cancellation are impractical for sequencing purposes because they account for too few hours of scheduled OR time. Effort invested in identifying and resequencing cases at high risk for cancellation likely has limited value.

Decompression illness (DCI) is caused by bubble formation in the blood or tissues after a reduction in ambient pressure. Clinically, DCI may range from a trivial illness to paralysis, loss of consciousness, cardiovascular collapse, and death. Recompression is the universally accepted standard for the treatment of DCI. When recompression is delayed, a number of strategies have been suggested to improve the outcome. We examined the effectiveness and safety of both recompression and adjunctive therapies in the treatment of DCI.

We searched CENTRAL (Cochrane Central Register of Controlled Trials) (The Cochrane Library 2009, Issue 2); MEDLINE (Medical Literature Analysis and Retrieval System Online) (1966 to July 2009); CINAHL (Cumulative Index to Nursing and Allied Health Literature) (1982 to July 2009); EMBASE (Excerpta Medica Database) (1980 to July 2009); the Database of Randomized Controlled Trials (RCTs) in Hyperbaric Medicine (July 2009); and hand-searched journals and texts. We included RCTs that compared the effect of any recompression schedule or adjunctive therapy with a standard recompression schedule and applied no language restrictions. Three authors extracted the data independently. We assessed each trial for internal validity and resolved differences by discussion. Data were entered into RevMan 5.0 software (Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration, 2008).

Two RCTs satisfied the inclusion criteria. Pooling of data was not possible. In one study, there was no evidence of improved effectiveness with the addition of a nonsteroidal antiinflammatory drug to routine recompression therapy (at 6 weeks: relative risk 1.04, 95% confidence interval [CI]: 0.90–1.20, P = 0.58), but there was a reduction in the number of recompression treatments required when tenoxicam was added (P = 0.01, 95% CI: 0–1). In the other study, the odds of multiple recompressions were lower with a helium and oxygen (heliox) table compared with an oxygen treatment table (relative risk 0.56, 95% CI: 0.31–1.00, P = 0.05).

Recompression therapy is the standard for treatment of DCI, but there is no RCT evidence. The addition of a nonsteroidal antiinflammatory drug (tenoxicam) or the use of heliox may reduce the number of recompressions required, but neither improves the odds of recovery. The application of either of these strategies may be justified. The modest number of patients studied demands a cautious interpretation. Benefits may be largely economic, and an economic analysis should be undertaken. There is a case for large randomized trials of high methodological rigor to define any benefit from the use of different breathing gases and pressure profiles during recompression.

Our previous studies demonstrated that intrathecal lidocaine treatment could produce prolonged reversal of established hyperalgesia or allodynia, both induced by chronic constriction injury. Indeed, intrathecal lidocaine treatment remarkably suppressed the activation of p38 mitogen-activated protein kinase (MAPK) in hyperactive microglia. In the present study we suggest that lidocaine may act directly on the microglia and attenuate the release of cytokines.

We assessed the influence of lidocaine on the levels of phospho-p38 MAPK, tumor necrosis factor- (TNF-), interleukin-1beta (IL-1β), IL-6, and intracellular calcium triggered by extracellular adenosine triphosphate (ATP) in cultured rat microglia. Our experimental methods included Western blot, real-time reverse transcription–polymerase chain reaction, enzyme-linked immunosorbent assay, and calcium imaging.

We found that lidocaine (in a dose-dependent manner) significantly attenuated p38 MAPK activation triggered by 1 mM ATP, by inhibiting the transcription of 3 cytokine messenger RNAs and causing a decrease in their respective protein concentrations (TNF-, IL-1β, and IL-6, P < 0.05, vs. the ATP group). SB203580, an antagonist of P38, attenuated ATP-activated elevation in protein levels of TNF-, IL-1β, and IL-6 in the microglia. The high level of intracellular calcium ([Ca²⁺]i) that is induced by ATP was decreased by the addition of 10 mM lidocaine (P < 0.05 vs. the ATP group).

These findings indicate that lidocaine can directly act on microglia. Lidocaine, by inhibiting the increase of intracellular calcium, also inhibited p38 MAPK activation and attenuated the production of proinflammatory cytokines (including TNF-, IL-1β, and IL-6), which were triggered by extracellular ATP in cultured rat microglia.

Although it has been reported that local anesthetics, especially lidocaine, are cytotoxic, the mechanism is unclear. Depolarization of the mitochondrial membrane potential (m), one of the markers of mitochondrial failure, is regulated by the proton electrochemical gradient ( H⁺). Therefore, intracellular pH ([pH]in) and mitochondrial pH ([pH]m) are important factors for modifying m. However, the effects of local anesthetics on [pH]in and [pH]m are unclear. To investigate mitochondrial responses to local anesthetics, we simultaneously measured [pH]m and [pH]in, along with m.

The ratiometric fluorescent probe JC-1 and HPTS were used for the simultaneous measurements of m with [pH]in in rat dorsal root ganglion neurons. A carboxy-SNARF-1 fluorescent probe was used to measure [pH]m. Lidocaine, mepivacaine, bupivacaine, procaine, QX-314, a charged form of lidocaine, and ammonium chloride (NH₄Cl) were evaluated.

m was depolarized and [pH]in was increased by lidocaine, mepivacaine, bupivacaine, and procaine in a dose-dependent manner. Significantly, a relationship between m and [pH]in was observed for lidocaine, mepivacaine, bupivacaine, procaine, and NH₄Cl perfusion. In contrast, QX-314 did not change m or [pH]in. In low-pH saline (pH6) and in the presence of a weak acid, lidocaine failed to increase [pH]in or depolarize m. The [pH]m was also increased by lidocaine, mepivacaine, bupivacaine, procaine, and NH₄Cl.

These results demonstrate that uncharged (base) forms of local anesthetics induce m depolarization. One of the causes is intracellular and mitochondrial alkalization.

Pulsed radiofrequency (PRF) is a popular pain treatment modality. The effect of PRF current on neuropathic pain has not been examined in detail. We investigated the effect of PRF current on mechanical allodynia induced with resiniferatoxin (RTX) in rats, especially regarding the influence of the duration of allodynia before PRF procedures and that of exposure time to PRF.

Adult male Sprague-Dawley rats (weighing 250–400 g) received a single intraperitoneal injection of RTX (200 µg/kg) under 2

to 3% sevoflurane anesthesia. Rats in group S₂ (n = 5) were assigned to receive PRF current to the right sciatic nerve for 2 minutes 1 week after RTX treatment; rats in group M₂ (n = 6), PRF current for 2 minutes 3 weeks after RTX treatment; rats in group L₂ (n = 7), PRF current for 2 minutes 5 weeks after RTX treatment; rats in group S₄ (n = 5), PRF current for 4 minutes 1 week after RTX treatment; rats in group S₆ (n = 5), PRF current for 6 minutes 1 week after RTX treatment; and rats in group S₀ (n = 3), no PRF current was delivered. Instead, the needle and electrode were inserted at proper points for 6 minutes 1 week after RTX treatment. All rats were evaluated for sensitivity to mechanical stimulation with von Frey filaments and to thermal stimulation with a thermal testing apparatus and for motor function using placing and grasping reflexes before injection of RTX, every week after injection of RTX, and 1, 2, 3, 4, and 5 weeks after PRF treatment.

The paw withdrawal thresholds of both hindpaws 1 week after RTX treatment were significantly lower than the pre-RTX baseline in all groups. In groups S₂, S₄, S₆, and M₂, after PRF procedures, the ipsilateral paw withdrawal thresholds significantly increased. A statistically significant difference was detected between the PRF-treated and PRF-untreated hindpaws. The ipsilateral–contralateral paw withdrawal thresholds after PRF procedures in group S₂ were significantly higher than those in groups M₂ and L₂. Between groups M₂ and L₂, significant differences were found 1, 2, 4, and 5 weeks after PRF procedures. The ipsilateral–contralateral paw withdrawal thresholds in group S₆ were significantly higher than those in groups S₂ and S₄ 5 weeks after PRF procedures. No significant difference was found between groups S₂ and S₄ at any time. After PRF procedures, no difference in the withdrawal latency after heat stimulation and no motor disturbance were observed at any time in all groups.

PRF treatment was more effective when applied in the early stages of mechanical allodynia (1 week) in rats. Increased exposure time to PRF current from 2 to 6 minutes showed a significant antiallodynic effect without motor impairment. We propose the application of PRF current for 6 minutes adjacent to the nerve as soon as possible when allodynia appears.

IV lipid emulsion has demonstrated to be effective therapy for bupivacaine-induced cardiotoxicity. However, the role of epinephrine when coadministered with lipid emulsion in toxin-induced cardiac arrest is unclear. We postulated superior resuscitation outcome in the absence of epinephrine in a rabbit model of bupivacaine-induced cardiac arrest resuscitated with IV lipid emulsion.

Twenty sedated, instrumented New Zealand White rabbits received 10 mg/kg IV bupivacaine producing asystole. Mechanical ventilation and external chest compressions were commenced at 30 seconds. At 1 minute, animals received 5 mL/kg 20% lipid emulsion in addition to 1 of 4 additional IV treatments (n = 5 all groups): 0.9% saline, 2.5 µg/kg epinephrine, 10 µg/kg epinephrine, 100 µg/kg epinephrine; all at 1 mL/kg. Lipid emulsion bolus was repeated at 4 minutes. Return of spontaneous circulation and hemodynamic metrics were obtained to 15 minutes. Saline group animals additionally received high-dose epinephrine (100 µg/kg) treatment at 15 minutes, and were monitored to 20 minutes.

High-dose epinephrine administration was associated with increased rate of return of spontaneous circulation compared with saline control (0 of 5 saline-treated animals; 0 of 5 animals in the 2.5 µg/kg epinephrine group; 3 of 5 in the 10 µg/kg group [P = 0.167]; and 4 of 5 in the 100 µg/kg group [P = 0.048]). Spontaneous but decreasing circulation was maintained at 15 minutes in 4 of 5 animals in the 100 µg/kg group alone (P = 0.048); mean arterial blood pressure at 15 minutes was 12.8 (SEM 2.8) mm Hg saline, 12.0 (2.5) mm Hg 2.5 µg/kg epinephrine, 20.6 (2.7) mm Hg 10 µg/kg epinephrine, and 26.4 (3.9) mm Hg 100 µg/kg epinephrine (P = 0.008). Four of five animals in the saline-treated group exhibited return of spontaneous circulation after delayed epinephrine treatment (P = 0.048). High-dose epinephrine administration was associated with a significant increase in coronary perfusion pressure before return of spontaneous circulation.

Epinephrine seemed to be necessary for return of spontaneous circulation, but was subsequently associated with declining hemodynamic variables in this rabbit model of bupivacaine-induced cardiac arrest. Further study is required to define the role of epinephrine in lipid-based resuscitation from local anesthetic-induced cardiac arrest.

The transversus abdominis plane (TAP) block is a recently described technique involving injecting local anesthetic between the internal oblique and transversus abdominis layers of the abdominal wall. It has been shown to be effective in reducing morphine consumption and improving postoperative pain relief in several clinical settings.

We performed a randomized placebo-controlled trial comparing bilateral ultrasound-guided TAP blocks (2 x 20 mL 0.5% ropivacaine or 0.9% saline) in adult female patients undergoing midline laparotomy for known or presumed gynecological malignancy. Both groups received multimodal IV analgesia. The primary outcomes for the study were defined as the incidence of "inadequate" analgesia (defined as a score >50 mm on a visual analog scale) with forced expiration at 2 hours postoperatively and total postoperative morphine consumption at 2 hours and 24 hours.

Data from 65 patients were included in the study. The groups were comparable in terms of age, weight, surgical duration, and intraoperative morphine doses. There were no significant differences between the control and treatment groups in the proportion of patients with inadequate analgesia either at rest (39% vs. 22%, P = 0.13) or with coughing (61% vs. 53%, P = 0.54) at 2 hours. There was no significant difference in postoperative morphine consumption between the placebo and treatment groups at 2 hours (13.5 mg vs. 11.87 mg, P = 0.53) or 24 hours (34.0 mg vs. 36.1 mg, P = 0.76). There were no significant differences in the incidence of opioid side effects or patient satisfaction.

This study demonstrated that TAP blockade conferred no benefit in addition to multimodal analgesia in women undergoing major gynecological cancer surgery.

Intravascular and intramuscular injection of local anesthetics during lumbar sympathetic ganglion block (LSGB) can cause false positive or negative results in a diagnostic block, and complications. In the present study, we prospectively evaluated the incidence and possible factors causing intravascular and IM injection during LSGB.

We evaluated 216 LSGBs in 83 patients. All LSGBs were performed by 1 of the authors using a 3-needle technique. After final needle position was confirmed by biplanar fluoroscopy, an aspiration test was conducted, and 1 mL of contrast was injected sequentially. Incidences of psoas muscle injection, blood flashback, and the presence of intravascular contrast spread on static and real-time fluoroscopy were assessed.

The incidence of psoas muscle injection of contrast was 21.3% (46/216), and it was associated with the level of injection (L2) significantly (² = 14.773, P = 0.001). The incidence of intravascular injection of contrast was 12.5% (27/216). Among 27 cases of documented intravascular injections, 5.1% (11/216) of patients showed contrast spread at the area where the sympathetic ganglion was presumed to be and to the vessels simultaneously, and 7.4% (16/216) of patients showed only intravascular injection of contrast. The sensitivity of the aspiration test and static radiography were 40.7% and 70.4%, respectively.

LSGB at the L2 level showed the lowest incidence of psoas muscle injection of contrast in comparison with LSGB at L3 and L4. The aspiration test and static radiography frequently missed the intravascular injection of contrast during LSGBs.

Anesthesiologists may insert needles through ultrasound gel when performing ultrasound-guided regional anesthesia. In this study, it was determined whether needles carry gel into tissues.

Ultrasound gel dyed blue was applied to pork rashers. Tuohy and short-bevel needles were passed through the gel and pork. The needles were then assessed for the presence of ultrasound gel.

All needles, including those with stylets, carried gel and tissue within the lumen.

Ultrasound gel may be injected around (and perhaps in) nerves during regional anesthesia procedures. Studies are needed to determine the implications of this practice.