Masayuki Shibasaki

Induction of high mobility group box-1 in dorsal root ganglion contributes to pain hypersensitivity after peripheral nerve injury

&NA; Pro‐inflammatory cytokine high mobility group box‐1 (HMGB‐1) is involved in inflammation in the central nervous system, but less is known about its biological effects in the peripheral nervous system. In the present study, the role of HMGB‐1 in the primary afferent nerve was investigated in the context of the pathophysiology of peripheral nerve injury‐induced pain hypersensitivity. Real‐time PCR confirmed an increase in HMGB‐1 mRNA expression in the dorsal root ganglion (DRG) and spinal nerve at 1 day after spinal nerve ligation (SNL). Induction of HMGB‐1 mRNA was observed in both injured L5 and uninjured L4. Immunohistochemistry for HMGB‐1 revealed that SNL‐induced HMGB‐1 expression in the primary afferent neurons and satellite glial cells (SGCs) in the DRG, and in Schwann cells in the spinal nerve. Up‐regulation of HMGB‐1 was associated with translocation of its signal from the nucleus to the cytoplasm. Injection of HMGB‐1 into the sciatic nerve produces transient behavioural hyperalgesia. Neutralizing antibody against HMGB‐1 successfully alleviated the mechanical allodynia observed after SNL treatment. Receptor for advanced glycation end products (RAGE), one of the major receptors for HMGB‐1, was expressed in the primary afferent neurons and SGCs in the DRG, as well as in Schwann cells in the spinal nerve. These results indicate that HMGB‐1 is synthesized and secreted into the DRG and spinal nerve, and contributes to the development of neuropathic pain after nerve injury. Blocking HMGB‐1/RAGE signalling might thus be a promising therapeutic strategy for the management of neuropathic pain.

Prediction of pediatric endotracheal tube size by ultrasonography.

Background:Formulas based on age and height often fail to reliably predict the proper endotracheal tube (ETT) size in pediatric patients. We, thus, tested the hypothesis that subglottic diameter, as determined by ultrasonography, better predicts optimal ETT size than existing methods. Methods:A total of 192 patients, aged 1 month to 6 yr, who were scheduled for surgery and undergoing general anesthesia were enrolled and divided into development and validation phases. In the development group, the optimal ETT size was selected according to standard age-based formulas for cuffed and uncuffed tubes. Tubes were replaced as necessary until a good clinical fit was obtained. Via ultrasonography, the subglottic upper airway diameter was determined before tracheal intubation. We constructed a regression equation between the subglottic upper airway diameter and the outer diameter of the ETT finally selected. In the validation group, ETT size was selected after ultrasonography using this regression equation. The primary outcome was the fraction of initial cuffed and uncuffed tube sizes, as selected through the regression formula, that proved clinically optimal. Results:Subglottic upper airway diameter was highly correlated with outer ETT diameter deemed optimal on clinical grounds. The rate of agreement between the predicted ETT size based on ultrasonic measurement and the final ETT size selected clinically was 98% for cuffed ETTs and 96% for uncuffed ETTs. Conclusions:Measuring subglottic airway diameter with ultrasonography facilitates the selection of appropriately sized ETTs in pediatric patients. This selection method better predicted optimal outer ETT diameter than standard age- and height-based formulas.

Increased platelet, leukocyte, and endothelial cell activity are associated with increased coagulability in patients after total knee arthroplasty.

Background:  Orthopedic surgery, especially total knee and total hip arthroplasty, is considered a risk factor for peri‐operative venous thromboembolism.

Peripheral sensitization caused by insulin-like growth factor 1 contributes to pain hypersensitivity after tissue injury

&NA; Sensitization of primary afferent neurons is one of the most important components of pain hypersensitivity after tissue injury. Insulin‐like growth factor 1 (IGF‐1), involved in wound repair in injured tissue, also plays an important role in maintaining neuronal function. In the present study, we investigated the effect of tissue IGF‐1 on nociceptive sensitivity of primary afferent neurons. Local administration of IGF‐1 induced thermal and mechanical pain hypersensitivity in a dose‐dependent manner, and was attenuated by IGF‐1 receptor (IGF1R) inhibition. Tissue but not plasma IGF‐1 levels, as determined by enzyme‐linked immunosorbent assay, significantly increased after plantar incision. Immunohistochemistry revealed that IGF1R was predominantly expressed in neurons as well as in satellite glial cells in the dorsal root ganglion (DRG). Double‐labeling immunohistochemistry showed that IGF1R expression colocalized with peripherin and TRPV1, but not with NF200 in DRG neurons. The IGF1R inhibitor successfully alleviated mechanical allodynia, heat hyperalgesia, and spontaneous pain behavior observed after plantar incision. Expression of phosphorylated Akt in DRG neurons significantly increased after plantar incision and was suppressed by IGF1R inhibition. These results demonstrate that increased tissue IGF‐1 production sensitizes primary afferent neurons via the IGF1R/Akt pathway to facilitate pain hypersensitivity after tissue damage. Insulin‐like growth factor 1 is synthesized locally after tissue injury and contributes to the sensitization of primary afferent neurons.

Ultrasound-guided radial artery catheterization in infants and small children.

Objective: To determine whether ultrasound guidance increases the success rates, decreases the complication rates, and shortens the time to successful radial artery catheterization in infants and small children. Design: Randomized study. Setting: Single university-affiliated hospital. Patients: Infants and children weighing 3–20 kg, undergoing cardiac surgery for congenital heart disease. Intervention: We randomly assigned the right and left radial arteries of patients undergoing arterial catheterization to ultrasound-guided technique versus the usual palpation technique. Measurements: The primary study endpoints were the rates of successful cannulation at first and within three attempts. The secondary endpoints were time to radial artery identification, number of attempts for successful cannulation, and rate of complications. Main Results: Compared with palpation, ultrasound-guided radial artery catheterization was successful in 76.3% versus 35.6% of first attempts and in 94.9% versus 50.8% of arteries after three attempts (both comparisons, p < 0.01). The median time [interquartile range] to identification of the arteries (18.5 seconds [11.25–27.25] vs 30 seconds [17.75–39.5]) was significantly shorter (p < 0.01), the number of attempts [interquartile range] at successful cannulation (1 [1–1] vs 2 [1–2]) was significantly fewer (p < 0.01), and the proportion of hematomas (5.1% vs 25.4%) was significantly lower (p < 0.01) in the ultrasound group than those in the palpation group. Conclusions: In infants and small children, ultrasound-guided radial artery catheterization was more successful and expeditious than the usual palpation technique.

A novel method for ultrasound-guided radial arterial catheterization in pediatric patients.

BACKGROUND:Radial arterial catheterization in pediatric patients is occasionally difficult despite ultrasound guidance. We therefore assessed the factors affecting catheterization and tested an intervention designed to improve its success. METHODS:For initial assessment, we performed multiple logistic regression analyses using 102 pediatric patients. Dependent variables included first-attempt and overall success or failure; independent variables were systolic blood pressure, weight, ASA physical status, trisomy 21, arterial diameter, and subcutaneous depth of the radial artery (<2, 2–4, ≥4 mm). The effect of subcutaneous arterial depth on cannulation success was assessed using Kaplan-Meier curves with log-rank and Dunn tests. We then assessed catheterization success in 60 patients who were randomized to no treatment or subcutaneous saline injection, as necessary, to increase the subcutaneous arterial depth from <2 to 2 to 4 mm. RESULTS:Subcutaneous arterial depth of 2 to 4 mm was derived as a significant independent predictor of initial and overall success from the multiple logistic regression analyses. The 2 to 4 mm group had a significantly shorter catheterization time compared with the other 2 groups in the log-rank test (2–4 vs <2 mm group; P = 0.01, 2–4 vs ≥4 mm group; P < 0.001), and higher success rate in the first attempt (<2 [43.8%] vs 2–4 mm [76.9%], P = 0.02; 2–4 [76.9%] vs ≥4.0 mm [19.4%], P < 0.001), and the overall attempt (<2 [62.5%] vs 2–4 mm [89.7%], P = 0.04; 2–4 [89.7%] vs ≥4.0 mm [51.6%], P = 0.002). Injecting subcutaneous saline to bring arterial depth from <2 mm to 2 to 4 mm significantly shortened catheterization time (P = 0.002), and improved the success rate in the first-attempt (saline injection [85.0%] vs <2 mm [30.0%], P < 0.001), and the overall attempt (saline injection [90.0%] vs <2 mm [55.0%], P = 0.02). CONCLUSIONS:Ultrasound-guided radial artery catheterization in pediatric patients was fastest and most reliable when the artery was 2 to 4 mm below the skin surface. For arteries located <2 mm below the skin surface, increasing the depth to 2 to 4 mm by subcutaneous saline injection reduced catheterization time and improved the success rate.

Acute development of superior vena cava syndrome after pediatric cardiac surgery

and severity of agitation developing after tonsillectomy with sevoflurane anesthesia in children, did not lead to an increased incidence of side effects, and also provided smooth extubation (2). Also, Hanamoto et al. (1) have suggested that using dexmedetomidine might be better before extubation in their case report. Concordant to Hanamoto et al., we considered and started using dexmedetomidine before the extubation. We provided adequate sedation and smooth extubation with dexmedetomidine without respiratuar adverse effects and agitation in our patient. In conclusion, we can say that dexmedetomidine may be an appropriate anesthetic agent with sedative, analgesic, and anxiolytic properties in these patients. Esra Cal ıskan Nesr ın Bozdogan Aysu Kocum Mesut Sener An ıs Ar ıbogan Department of Anesthesiology, Faculty of Medicine, Baskent University, Ankara, Turkey (email: esra_ertr@yahoo.com)

Phosphodiesterase 3 Inhibition Reduces Platelet Activation and Monocyte Tissue Factor Expression in Knee Arthroplasty Patients

Background:Tissue damage during surgery activates platelets and provokes a prothrombic state. The current study attempted to determine the impact of phosphodiesterase 3 inhibitors on platelet activation, platelet–leukocyte aggregate formation, and monocyte tissue factor expression during and after total knee arthroplasty. Methods:Thirty-four patients undergoing scheduled total knee arthroplasty were randomly assigned to receive either the phosphodiesterase 3 inhibitor milrinone or the same amount of saline perioperatively. The effects of milrinone on platelet and leukocyte function in vitro were then assessed in healthy volunteers. Results:Perioperative infusion of milrinone significantly attenuated platelet activation; phosphorylation of intraplatelet p38 mitogen-activated protein kinase, extracellular signal–regulated kinase 1/2, and Akt; and platelet–leukocyte aggregation. Furthermore, perioperative tissue factor expression on monocytes and fibrin monomer complex production were reduced by milrinone infusion in patients undergoing total knee arthroplasty. In vitro studies using adenosine diphosphate– and collagen–stimulated blood samples from healthy volunteers confirmed the antiplatelet effects and reduced monocyte tissue factor expression by milrinone. These studies further showed that platelet aggregation and integrin &agr;IIb&bgr;3 activation were modified by intraplatelet phosphatidylinositol 3-kinase/Akt and mitogen-activated protein kinase/extracellular signal–regulated kinase pathways, and that P-selectin expression on platelets and platelet–leukocyte aggregation were modulated by intraplatelet p38 mitogen-activated protein kinase pathway. Conclusion:Continuous milrinone infusion has the potential to reduce platelet activation and monocyte tissue factor expression during the perioperative period in total knee arthroplasty. These events may be mediated in part by the ability of milrinone to reduce activation of intraplatelet mitogen-activated protein kinases and phosphatidylinositol 3-kinase. The clinical impact of phosphodiesterase 3 inhibition on perioperative hemostasis remains to be elucidated.

A portable blood analyzer that uses on-line data management to deliver higher-quality patient information

We constructed an on-line data management system and linked it to the communication protocol of a portable blood analyzer (i-STAT) in each operating room of our institution. We developed a new program that integrates circulatory dynamics data from a monitor with laboratory data from the i-STAT. Our new program permits the results to be viewed through an intranet using a novel prototype communication device for the i-STAT 300F. We verified that this system can improve the quality of patient care both bedside and in the monitoring room and compared the costs of blood testing using a conventional desktop blood-gas analyzer and using the i-STAT. We found that the novel integration of circulatory dynamics with laboratory data enhanced the quality of intraoperative patient monitoring and reduced the cost and work load of doctors working in the operating room.

Intraoperative monitoring of movement of an entrapped coronary guidewire by transesophageal echocardiography.

A 64-yr-old man with acute myocardial infarction was referred for emergency percutaneous coronary artery stent placement in the left anterior descending coronary artery and in the first diagonal branch. During the intervention, the deployed left anterior descending stent entrapped the guidewire placed in the first diagonal branch. Efforts to percutaneously retrieve the fragmented wire using a snare wire failed. Preoperative radiograph fluoroscopy images indicated that the proximal end of the fractured wire might be located in the aortic root or the proximal ascending aorta or the proximal aortic arch. The patient’s hemodynamics was stable, and regional as well as global ventricular and valvular function remained unchanged after this event. However, emergency surgery was planned to avoid thrombus formation, prevent embolic events and maintain coronary circulation. The surgical strategy was to establish conventional cardiopulmonary bypass with an arterial cannula inserted into the ascending aorta under anterograde intermittent cold sanguineous cardioplegic arrest with an aortic cross-clamp. The entrapped guidewire was to be manually retrieved after opening the aortic root, followed by coronary artery bypass grafting. As aortic clamping might pinch the wire, the original plan was to temporarily and partially reopen the cross-clamp at the moment of retrieval. Intraoperative transesophageal echocardiography (TEE) located the highly echogenic wire fragment in the ostium of the left main coronary artery and the ascending aorta (Figs. 1A and B; Video Clip 1; please see video clip available at www.anesthesia-analgesia.org), with the proximal end in the distal portion of the aortic arch (Figs. 1B and C). Upon commencement of aortic cannula flow, TEE revealed that the guidewire had migrated backwards toward the aortic root, allowing safe application of the aortic cross-clamp without trapping the wire fragment between the jaws of the clamp. (Figs. 2A and B, Video Clip 2; please see video clip available at www. anesthesia-analgesia.org). Thus, the proximal end of the retained wire was effortlessly retrieved after opening the aortic root. The distal end of the entrapped wire was also easily withdrawn from the coronary artery (Fig. 3). After completion of the coronary bypass, the patient was uneventfully weaned from cardiopulmonary bypass and subsequently recovered without neurological sequelae.