Lidocaine and bupivacaine exert differential effects on whole blood coagulation.

STUDY OBJECTIVES: To compare bupivacaine to lidocaine's effects on blood clotting at two concentrations, and to characterize and determine relative effects of two equianalgesic bupivacaine and lidocaine concentrations. DESIGN: Prospective, dual-controlled, whole blood equal volume admixture thrombelastographic (TEG) study. SETTING: University of Pennsylvania Medical Center operating rooms. PATIENTS: 20 ASA physical status I and II patients' blood comprised control groups and anesthetic groups. INTERVENTIONS: Analysis of whole blood clotting used six TEG channels for untreated and saline controls and four final concentrations (1.0% lidocaine, 0.5% lidocaine, 0.25% bupivacaine, and 0.125% bupivacaine) of local anesthetics. Saline control and the local anesthetic-treated specimens underwent 8.3% hemodilution. MEASUREMENTS AND MAIN RESULTS: Blood was studied. Saline control or four anesthetic solutions (30 microliters) were added in random order two 5 TEG cuvettes. Whole blood (330 microliters) was mixed ex vivo at 37 degrees C. A sixth channel with untreated whole blood (360 microliters) acted as an undiluted control. Data for four TEG parameters [reaction time (r), angle (alpha), maximum amplitude (MA), and percent decrease in TEG amplitude from MA 30 minutes after MA acquisition (Lysis 30)] for undiluted control and saline volumetric controls were compared to each other using Student's t-test for paired observations. Lidocaine and bupivacaine groups' TEGs were compared to the paired saline control analysis of variance for repeated measures. A p-value less than 0.05 was considered significant. There was no difference between whole blood and saline control TEGs. All local anesthetics produced significant hypocoagulable changes from control. Angle alpha and MA were significantly decreased in all local anesthetic groups. Ther time was prolonged only in the high lidocaine-treated blood. Lysis was a feature of the low lidocaine and bupivacaine solutions. Equianalgesic lidocaine produced more profound hypocoagulable effects than did bupivacaine. CONCLUSIONS: Lidocaine and bupivacaine both significantly impaired TEG coagulation in a concentration-dependent manner. Lidocaine was significantly more hypocoagulable than bupivacaine at two similarly analgesic concentrations.

Differential effects of serial hemodilution with hydroxyethyl starch, albumin, and 0.9% saline on whole blood coagulation.

STUDY OBJECTIVES: To determine by thrombelastography assessed coagulation, the effects of progressive hemodilution with three intravascular volume expanders. DESIGN: Prospective, controlled, whole blood, volumetric ex vivo hemodilution study. SETTING: University of Pennsylvania Medical Center Operating Rooms. PATIENTS: 60 ASA physical status I and II patients; phlebotomy prior to administration of IV fluids or medications. INTERVENTIONS: Analysis of whole blood clotting determined by six thrombelastographic channels for control and five volumetric hemodilutions (11%, 25%, 33%, 50%, and 75%) with 0.9% saline, 5% albumin, and 6% hydroxyethyl starch (n = 20 for each diluent group). MEASUREMENTS AND MAIN RESULTS: Thrombelastographic parameters R (minutes), angle alpha (degree), MA (mm), and lysis (%) were measured and compared to the sample control for each dilution of the same specimen. There was no significant difference between control groups in any thrombelastographic variable (R, angle alpha, MA, or lysis). No changes were seen in any variable from any diluent at 11% hemodilution. Seventy-five percent hemodilution caused significantly hypocoagulable changes from control for all thrombelastographic parameters for all three diluents. Thrombelastographic indices differed significantly from controls at intermediate hemodilutions. Both colloids caused decreases in measured angle alpha and MA at lower hemodilution than did 0.9% saline. Albumin 5% caused significant hypocoagulable changes from control values at lower hemodilution than did either 0.9% saline or 6% hydroxyethyl starch for all thrombelastographic parameters. Saline 0.9% increased angle alpha significantly at 50% hemodilution. Abnormal lysis did not occur at any dilution. Differing ex vivo effects of three different intravascular fluids thrombelastography assessed coagulation are found. CONCLUSION: No differences were found after 11% hemodilution with any volume expanders. Hemodilution with up to 50% saline maintained thrombelastographic indices. Albumin produced early and profound hypocoagulable effects. Significant hypocoagulability occurred for all three diluents at 75% hemodilution. The study supports the use of albumin in patients at risk for thrombosis, and saline in patients with a need for normal hemostasis.

Spinal kappa1 and kappa2 opioid binding sites in rats, guinea pigs, monkeys and humans.

Several lines of work demonstrate that there are two subtypes of kappa opioid receptors. Intrathecally administered agonists for the kappa1 subtype are not effective in treating pain, whereas agonists for the kappa2 receptor are anti-hyperalgesic and anti-allodynic. The question addressed here was whether the ratio of spinal kappa1 to kappa2 receptors was conserved across species. Thus, binding experiments were performed on spinal cord membranes from rats, guinea pigs, monkeys and humans. We found that kappa2 receptors were approximately ten times more abundant than kappa1 receptors in all species tested. This suggests that the anti-hyperalgesic and anti-allodynic properties of kappa2 agonists may also be conserved. Therefore, selective kappa2 agonists may be effective in treating chronic pain in humans.

Lidocaine inhibits blood coagulation: implications for epidural blood patch.

Lidocaine in the epidural space, through inhibitory effects upon coagulation, may contribute to inefficacy of epidural autologous blood patch (EBP). This study was undertaken to evaluate the effect of achievable epidural concentrations of lidocaine on blood coagulation as a step in testing this hypothesis. Ex vivo blood coagulation using whole blood (n = 20) was studied with computerized thrombelastography (TEG). Each blood specimen was exposed to serial dilutions of lidocaine hydrochloride or saline to form end-concentrations of 0.0 mM, 2.3 mM, 4.6 mM, 9.2 mM, 18.5 mM, and 36.9 mM lidocaine. Statistical analysis using analysis of variance for repeated measures revealed that the three highest lidocaine concentrations tested caused hypocoagulable and/or fibrinolytic changes as compared with controls. Achievable epidural admixtures of lidocaine and whole blood will impair coagulation. Therefore, residual lidocaine in the epidural space may contribute to failures of immediate or early EBP.

Midtrimester thyroidectomy in the ovine fetus.

Six lamb fetuses at 63-101 days gestation had thyroidectomy (Thx) and were investigated at term for weights, radiologic study, serum thyroxine (T4), and thyroid-stimulating hormone concentrations (TSH), electron-microscopic lung examination, acid base, blood flow, EEG, and brain metabolism. Compared to age-matched controls, body weight was significantly reduced (P less than .025). Brain and lung weights were reduced but not significantly. Brain weight as a percent of body weight was significantly increased in Thx fetuses (Thx = 1.85% +/- 0.18; control = 1.41% +/- 0.08; P less than .025). Hemoglobin was reduced (P less than .025), as was O2 content (P less than .005) and cerebral blood flow (P less than .05). Fetal T4 was low (Thx = 4.1 +/- 1.7 microgram %, control = 9.4 +/- 1.3 microgram %); (P less than .05). Fetal Thx cortisol, calcium, phosphate, glucose, lactate, pH, pO2, pCO2, O2 saturation, heart rate, and blood pressure remained unchanged. Thx-fetal brain O2 consumption and glucose consumption, as well as lactate production, were unchanged. EEG showed no consistent pattern of change regarding maturity, but did show immaturity with the two lowest T4 levels. Bone microradiographs showed growth and maturity retardation, specifically delayed epiphyseal closure, endochrondral ossification, and lack of secondary ossification centers in Thx fetuses. Electron-microscopic examination of lung showed Thx fetuses had fewer lamellar bodies in type II cells, fewer type II cells, and more glycogen granules. Thx causes fetal reduction of T4 and anemia, delays lung maturation and bone growth and maturation.(ABSTRACT TRUNCATED AT 250 WORDS)