Low predictability of three different noninvasive methods to determine fluid responsiveness in critically ill children.

OBJECTIVE: To predict fluid responsiveness by noninvasive methods in a pediatric critical care population. DESIGN: Prospective observational clinical trial. SETTING: PICU in a tertiary care academic hospital. PATIENTS: Thirty-one pediatric patients aged from 1 day to 13 years under mechanical ventilation and on catecholamine support. INTERVENTIONS: We tested three noninvasive methods to predict fluid responsiveness: an esophageal Doppler system (CardioQ), a pulse contour analysis algorithm system (LiDCOrapid), and respiratory variations in vena cava inferior diameter. Stroke volume index was measured by transthoracic echocardiography before and after fluid challenge to determine fluid responders. Infusion of 10 mL/kg hydroxyethylstarch 130/0.4. MEASUREMENTS AND MAIN RESULTS: Predictability of fluid responsiveness was only found in Doppler peak velocity of descending aortal blood flow. Increased peak velocity with reduction after fluid bolus was predictive for nonresponding to IV fluid challenge. Sensitivity and specificity of peak velocity were 69% and 73%, respectively. The cut point was set at 135.5 cm/s. The lower the Doppler peak velocity, the higher was the probability for a fluid response. Neither stroke volume variations nor respiratory variations in vena cava inferior diameter during mechanical ventilation were useful in predicting fluid responsiveness in this pediatric patient population. None of the children had abdominal hypertension measured by bladder pressure. CONCLUSIONS: Dynamic preload variables such as stroke volume variation or respiratory variations in vena cava inferior diameter may not be useful for predicting fluid responsiveness in certain pediatric patient populations. Esophageal Doppler peak velocity was predictive of fluid responsiveness where a target value of more than 135,5 cm/s may be a signal to terminate further fluid challenges. This target value may be different in different age groups, as esophageal Doppler peak velocity varies with age.

Auricular acupuncture effectively reduces state anxiety before dental treatment--a randomised controlled trial.

OBJECTIVES: The objective of this study was to analyse whether auricular acupuncture, acupuncture at the outer ear, could reduce state anxiety before dental treatment. METHODS: This prospective, randomised patient-blinded study with 182 patients compared anxiety before dental treatment following auricular acupuncture at the relaxation-, tranquillizer- and master cerebral points (auricular acupuncture group) versus acupuncture at sham points (finger-, shoulder- and tonsil points; sham group) and a non-intervention control group. Anxiety was assessed using the Spielberger State Trait Anxiety Inventory (German version) before auricular acupuncture and 20 min thereafter, immediately before dental treatment. RESULTS: Auricular acupuncture reduced state anxiety score more effectively from 54.7 ± 10.8 to 46.9 ± 10.4 (mean ± SD) than sham acupuncture from 51.9 ± 10.2 to 48.4 ± 10.0. In contrast, state anxiety in the control group increased from 51.0 ± 11.7 to 54.0 ± 11.6 (mean increase +3.0; CI +4.7 to +1.2). The decrease in state anxiety in both intervention groups was statistically significant (p < 0.001) when compared to the non-intervention control group. After correcting for group differences in baseline state anxiety, the reduction in anxiety was -7.3 score points (CI -9.0 to -5.6) in the auricular acupuncture group and -3.7 score points (CI -5.4 to -1.9) in the sham group (p = 0.008). CONCLUSION: Auricular acupuncture, a minimally invasive method, effectively reduces state anxiety before dental treatment. CLINICAL RELEVANCE: Auricular acupuncture could be an option for patients scheduled for dental treatment, who experience an uncomfortable degree of anxiety and request an acute intervention for their anxiety.

Median effective local anesthetic doses of plain bupivacaine and ropivacaine for spinal anesthesia administered via a spinal catheter for brachytherapy of the lower abdomen.

BACKGROUND AND OBJECTIVES: Continuous spinal anesthesia via a spinal catheter allows adjusting the duration and extent of anesthesia to surgical needs, maintenance of hemodynamic stability, and good postoperative analgesia. This study was designed to determine the median effective local anesthetic dose of plain ropivacaine and bupivacaine administered intrathecally for interstitial brachytherapy of the lower abdomen using the Dixon up-and-down method. METHODS: Forty patients were randomly allocated to receive either intrathecal bupivacaine 5 mg per mL or ropivacaine 10 mg per mL via a 24-gauge spinal catheter at the L3-4 interspace. The initial dose was 10 mg of bupivacaine or 20 mg of ropivacaine; the dosing intervals were 1 mg and 2 mg, respectively. Doses for subsequent patients were determined by the response of the previous patient in that group. Successful anesthesia was defined as a loss of sensation to a cold stimulus at the T6 level and full motor blockade within 20 minutes after administration of the local anesthetic. RESULTS: The median effective local anesthetic dose for intrathecal bupivacaine was 11.2 mg (95% confidence interval [CI], 10.3-12.1) and 22.6 mg for ropivacaine (95% CI, 20.5-24.6). A relative analgesic potency ratio of 0.50 (95% CI, 0.44-0.56) was calculated between the median effective local anesthetic dose of intrathecal bupivacaine and ropivacaine. CONCLUSIONS: Bupivacaine and ropivacaine are appropriate for continuous spinal anesthesia for interstitial radiation therapy procedures of the lower abdomen. In the dose-ranges investigated, intrathecal ropivacaine is approximately half as potent as bupivacaine.

Point-of-care platelet function tests: detection of platelet inhibition induced by nonopioid analgesic drugs.

Detection of platelet inhibition is of clinical relevance in the preinterventional risk-benefit assessment in chronic low-back-pain patients scheduled for invasive pain therapy. We evaluated the sensitivity of various point-of-care platelet function tests for the detection of platelet inhibition induced by nonopioid analgesic drugs. After Institutional Review Board approval and informed consent, citrated whole blood from 40 patients with chronic unspecific low back pain was investigated before and 30 min after intravenous infusion of the study medication consisting of diclofenac 75 mg (plus orphenadrin 30 mg; Neodolpasse; Fresenius Kabi Austria GmbH, Austria), parecoxib 40 mg (Dynastat; Pharmacia Europe EEIG, UK), paracetamol 1 g (Perfalgan; Bieffe Medital S.P.A., Italy), or normal saline in a randomized, cross-over, double-blinded, placebo-controlled study. Platelet function was assessed using the PFA-100 platelet function analyzer and thromboelastometry, as well as impedance aggregometry (in the last 17 patients recruited after it became commercially available). Sensitivity for detecting diclofenac-induced platelet inhibition was 85% for the PFA-100 using epinephrine as agonist and 94% for arachidonic acid-induced impedance aggregometry. ADP-induced platelet function tests, as well as cytochalasin D-modified thromboelastometry were unreliable. All tests had a low incidence of false-positive test results after normal saline. Paracetamol and parecoxib had no significant platelet inhibiting effect. The PFA-100 using epinephrine as agonist and arachidonic acid-induced impedance aggregometry are recommended for the detection of cyclooxygenase-I-inhibiting effects of nonsteroidal anti-inflammatory drugs such as diclofenac. Our findings confirm that a single rescue dose of paracetamol and parecoxib has no antiplatelet effect.

No evidence for direct modulatory effects of delta 9-tetrahydrocannabinol on human polymorphonuclear leukocytes.

The effects of cannabinoids (CB) that have been reported in various leukocyte populations were mainly immunosuppressive or immunomodulatory. Almost nothing is known, however, about direct interactions of cannabinoids with human polymorphonuclear cells (PMN), although m-RNA for the cannabinoid receptor-2 (CB(2)) was found in human PMN. In order to investigate a potential influence of cannabinoids on human PMN, the migration and phagocytosis of PMN were studied in the presence of Delta(9)-Tetrahydrocannabinol (Delta(9)-THC) at final concentrations between 10(-10) and 10(-5) M. No effect was detectable on these essential PMN functions; and besides, no CB(2)-receptor expression could be detected using the Western blotting technique. Thus, circulating human PMN from healthy individuals remain unaffected by Delta(9)-THC due to the absence of functional CB(2)-receptor expression.

Inhalational sevoflurane in severe bronchial obstruction unresponsive to multipharmacologic therapy: a case report.

INTRODUCTION: Bronchial asthma with respiratory failure is a challenge for the intensivist as mechanical ventilation is often difficult due to bronchoconstriction and air-trapping. We describe a case of severe asthma with respiratory acidosis in a 10-year-old patient unresponsive to multipharmacologic broncholytic therapy. Only the initiation of sevoflurane inhalation resolved severe bronchoconstriction and dynamic hyperinflation, leading to complete recovery. CASE PRESENTATION: A 10-year-old Caucasian boy was intubated and mechanically ventilated due to an asthmatic attack. Bronchoconstriction and dynamic hyperinflation were severe while multipharmacological broncholytic therapy was unsuccessful. Inhalation with sevoflurane via an anaesthesia machine was the key intervention leading to gradual resolving of severe hypercapnia and respiratory acidosis. Furthermore bilateral pupil dilation occurred during hypercapnia, but no intracranial pathology could be detected. The patient made an uneventful recovery. To our knowledge this is the first case where hypercapnia and respiratory acidosis were so profound and long lasting yet the patient survived without any damage. CONCLUSIONS: Inhalational anaesthetics must be considered as an early treatment option in ventilated asthmatic patients with bronchial obstruction unresponsive to conventional therapy even though their administration in intensive care units may be difficult.

Superior postoperative pain relief with thoracic epidural analgesia versus intravenous patient-controlled analgesia after minimally invasive pectus excavatum repair.

OBJECTIVE: Minimally invasive pectus excavatum repair is a common and painful surgical procedure in children and adolescents. Adequate postoperative pain therapy is important far beyond the immediate postoperative period because sensitization to painful stimuli can cause chronic pain or higher pain levels during subsequent surgical procedures. Although data in adults favor thoracic epidural anesthesia for pain control in thoracotomy, data for adolescents and children are scarce. We tested the hypothesis that pain relief with thoracic epidural analgesia was superior to that with intravenous patient-controlled analgesia after minimally invasive pectus excavatum repair in children and adolescents. METHODS: We performed a prospective randomized trial with adolescents who had undergone minimally invasive pectus excavatum repair to compare postoperative pain using two different postoperative pain therapy settings: intravenous patient-controlled analgesia (n = 20) with morphine versus continuous thoracic epidural analgesia (n = 20) with 0.2% ropivacain containing 2 microg/mL fentanyl. RESULTS: Forty patients (32 male and 8 female patients) aged 10 to 28 years were studied. The thoracic epidural analgesia group showed lower pain scores (P < .0001) and required less additional pain medication in conjunction with greater well-being postoperatively (P < .0001) compared with patients receiving patient-controlled intravenous morphine. There was no significant difference regarding the incidence of sedation (P = .38), nausea (P = .10), and pruritus (P = .72) in both groups. CONCLUSIONS: For adolescents undergoing minimally invasive pectus excavatum repair, thoracic epidural analgesia was superior to intravenous patient-controlled analgesia for postoperative analgesia, resulting in lower postoperative pain scores in conjunction with greater well-being.

The effects of high molecular weight hydroxyethyl starch solutions on platelets.

Physicochemical characteristics of hydroxyethyl starch (HES) molecules determine their side effects on hemostasis. Our aim in the present experiments was to test the antiplatelet effect of novel high molecular weight HES. Citrated whole blood was hemodiluted in vitro (0% and 20%) with either HES 550 (Hextend), HES 600 (6%Hetastarch-Baxter), HES 200 (Elohäst), or the solvent of Hextend in its commercially available solution. The availability of glycoprotein IIb-IIIa was assessed on nonstimulated and on agonist-induced platelets using flow cytometry. Glycoprotein IIb-IIIa availability increased significantly after hemodilution with Hextend and its solvent by 23% and 24%, respectively, but decreased in the presence of 6% Hetastarch-Baxter and Elohäst by 18% and 15%, respectively, with no significant difference between the latter two colloids. This study shows that Hextend does not inhibit platelet function as anticipated by its high molecular weight and degree of substitution. The unexpected platelet stimulating effect of Hextend is unique among the currently available HES preparations and may, at least in part, be induced by its solvent containing calcium chloride dihydrate (2.5 mmol/L). The platelet-inhibiting effect of 6%Hetastarch-Baxter was not significantly different from that of medium molecular weight HES 200.

The mechanical properties of continuous spinal small-bore catheters.

Continuous spinal anesthesia (CSA) has a nearly 100-yr history. In situations of difficult removal of a CSA small-bore catheter, mechanical properties of the different catheters might be important, because breakage could occur. We compared 5 different CSA small-bore catheters, 22- to 28-gauge from 3 manufacturers, for tensile strength, tensile stress, distension, and yield strength. Maximal tensile strength is the force applied before breakage of the catheter. The material characteristics of different CSA small-bore catheters for maximal tensile strength were: 22-gauge = 29.56 +/- 1.56 (mean +/- sd) Newton (N), 24-gauge = 16.77 +/- 1.61 N, 25-gauge = 9.20 +/- 0.48 N, 27-gauge = 4.61 +/- 0.25 N, 28-gauge = 5.07 +/- 0.59 N at room temperature. A strong correlation between maximal tensile strength and the outer diameter (r = 0.957, P < 0.001) and maximal tensile strength and the wall thickness (r = 0.9, P < 0.001) was observed. Although extrapolation from experimental studies to clinical routine should be made with care, our data suggest that catheters with higher-strength characteristics may reduce the risk of catheter breakage in patients, although clinical correlations are lacking.

The procoagulatory effects of delta-9-tetrahydrocannabinol in human platelets.

Delta-9-tetrahydrocannabinol (THC) is increasingly used for the long-term treatment of nausea, vomiting, cachexia, and chronic pain. Recent reports, however, have indicated an increased risk of myocardial infarction and thromboangiitis obliterans after THC intake. Blood platelets have an essential role in the pathogenesis of these two diseases, but it is unclear whether platelets are potential target cells for cannabinoids. We investigated the effects of THC on human platelets and the expression of cannabinoid receptors on their cell membranes in this in vitro study. The effects of THC (final concentrations 10(-7) to 10(-5) M) on the expression of activated platelet fibrinogen receptor (glycoprotein IIb-IIIa) and P selectin were characterized by flow cytometry. Western blotting was performed with platelet membrane preparations to determine the surface expression of cannabinoid receptors on human platelets. THC increased the expression of glycoprotein IIb-IIIa and P selectin on human platelets in a concentration-dependent manner. The two known cannabinoid receptors (CB(1) and CB(2)) were both detected on the cell membrane of human platelets. Our functional results may suggest a receptor-dependent pathway of THC-induced platelet activation. However, further in vivo studies are warranted to evaluate the role of cannabinoid receptors in mediating the demonstrated procoagulatory effect of THC.

Binding of hydroxyethyl starch molecules to the platelet surface.

Hydroxyethyl starch (HES) solutions impair platelet function by reducing the availability of the fibrinogen receptor. This effect is not mediated by intracellular signal transduction pathways. Also, an unspecific coating of platelets by HES macromolecules may be responsible for its antiplatelet effects. To test this hypothesis, we investigated the binding of fluorochrome-coupled HES to the surface of human platelets using whole blood flow cytometry. Citrated whole blood from 8 volunteers was incubated (5 min, 22 degrees C, in the dark) with fluorescein isothiocyanate (FITC)-coupled HES (200-kDa molecular weight, 0.5 degree of substitution, 0.042 molar ratio of FITC-conjugation) resulting in 0%, 1%, 3%, 5%, 10%, 20%, and 40% hemodilution. The percentage of platelets binding FITC-HES was determined using a FACSCalibur flow cytometer and CellQuestPro software. The percentage of FITC-positive platelets increased in a concentration-dependent manner reaching statistical significance at 10% hemodilution. Binding was independent of fibrinogen receptor blockade. The present experiments clearly demonstrate that extracellular binding of HES to the platelet surface is, at least in part, responsible for the antiplatelet effects of HES by blocking the access of ligands to the platelet fibrinogen receptor.