Endotracheal and endobronchial lidocaine administration: effects on plasma lidocaine concentration and blood gases

OBJECTIVE: To compare four different methods of endotracheal lidocaine administration with respect to the site of administration. DESIGN: Randomized controlled trial. SETTING: University hospital. PATIENTS: Thirty-two female patients (43.6 +/- 11.5 years old) undergoing elective gynecologic operations with an anesthesiologic risk classification not higher than ASA II. All patients gave their written informed consent to participate in the study. INTERVENTIONS: Lidocaine at a dose of 2 mg/kg, diluted with normal saline to a total volume of 10 mL, was administered to eight patients by instilling the drug solution from a 10-mL syringe directly into the outer aperture of the endotracheal tube. All other study patients received lidocaine under bronchoscopic control through the work channel of the bronchoscope either a) deep endotracheally, b) into the right main bronchus, or c) into the right lower lobe bronchus. At 10 points in time after drug administration, blood samples were taken for measurement of lidocaine plasma concentration (using high-pressure liquid chromatography) and blood gas analysis. MAIN MEASUREMENTS AND RESULTS: Therapeutic blood concentrations (greater than or equal to 1.4 micrograms/mL) could be achieved and toxic blood concentrations (greater than or equal to 6 micrograms/mL) could be avoided with all methods of administration. No significant difference was found between the different methods with regard to peak concentration, time to peak, onset and duration of therapeutic levels, or relative bioavailability. A significant (p less than .05) decrease in PaO2 to 75% of the baseline was seen with all methods used. CONCLUSIONS: Because no route of lidocaine administration was superior to the others, the simplest method (instillation into the endotracheal tube) should be used.     

Vasopressin improves vital organ blood flow after prolonged cardiac arrest with postcountershock pulseless electrical activity in pigs

OBJECTIVE: Although a benefit of vasopressin when compared with epinephrine was shown during cardiopulmonary resuscitation (CPR) after a short duration of ventricular fibrillation cardiac arrest, the effect of vasopressin during prolonged cardiac arrest with pulseless electrical activity is currently unknown. DESIGN: Prospective, randomized laboratory investigation using an established porcine model with instrumentation for measurement of hemodynamic variables, vital organ blood flow, blood gases, and return of spontaneous circulation. SETTING: University hospital laboratory. SUBJECTS: Eighteen domestic pigs. INTERVENTIONS: After 15 mins of cardiac arrest and 3 mins of chest compressions, 18 animals were randomly treated with either 0.8 units/kg vasopressin (n = 9) or 200 microg/kg epinephrine (n = 9). MEASUREMENTS AND MAIN RESULTS: Compared with epinephrine, vasopressin resulted, at both 90 secs and 5 mins after drug administration, in significantly higher (p < .05) median (25th-75th percentiles) left ventricular myocardial blood flow (120 [range, 96-193] vs. 54 [range, 11-92] and 56 [range, 41-80] vs. 21 [range, 11-40] mL/min/100 g, respectively) and total cerebral blood flow (85 [78-102] vs. 24 [18-41] and 50 [44-52] vs. 8 [5-23] mL/min/100 g, respectively). Spontaneous circulation was restored in eight of nine animals in the vasopressin group and in one of nine animals in the epinephrine group (p = .003). CONCLUSIONS: Compared with a maximum dose of epinephrine, vasopressin significantly increased left ventricular myocardial and total cerebral blood flow during CPR and return of spontaneous circulation in a porcine model of prolonged cardiac arrest with postcountershock pulseless electrical activity.     

Effects of acute administration of ethanol and the μ-opiate agonist etonitazene on thyroid hormone metabolism in rat brain

The effects of acute, low-dose administration of ethanol (1 g/kg bodyweight) and the μ-opioid receptor agonist etonitazene (30 μg/kg bodyweight) on the activities of the iodothyronine deiodinase isoenzymes were investigated in nine regions of the rat brain. The experiments were performed at three different times of the 24-h cycle (1300, 2100 and 0500 hours) and the rats were decapitated 30 and 120 min after administration of the respective drugs. Interest was focused on changes in the two enzymes that catalyze 1) 5′-deiodination of thyroxine (T₄) to the biologically active triiodothyronine (T₃), i.e. type II 5′-deiodinase (5′D-II) and 2) 5 (or inner-ring) deiodination of T₃ to the biologically inactive 3′3-T₂, i.e. type III deiodinase (5D-III). 120 min after administration of ethanol and etonitazene 5D-III activity was selectively inhibited in the frontal cortex (at 1300 and 1700 hours) and the amygdala (at all three measuring times). The 5′D-II activity was significantly enhanced 30 min after administration of etonitazene in the frontal cortex, amygdala and limbic forebrain, and after administration of ethanol in the amygdala alone. These effects on 5′D-II activity were seen at 2100 hours only. In conclusion, the two different addictive drugs both reduced the inactivation of the physiologically active thyroid hormone T₃ and enhanced its production. These effects occurred almost exclusively in the brain regions which were most likely to be involved in the rewarding properties of addictive drugs. As thyroid hormones have stimulating and mood-elevating properties, an involvement of these hormones in the reinforcing effects of addictive drugs seems conceivable. Received: 17 February 1997/Final version: 26 June 1997     

Intraosseous vasopressin improves coronary perfusion pressure rapidly during cardiopulmonary resuscitation in pigs.

OBJECTIVE: Intravenous administration of vasopressin during cardiopulmonary resuscitation (CPR) may be more effective than optimal doses of epinephrine. The main purpose of this study was to determine whether intraosseous vasopressin achieves serum drug levels comparable with intravenous doses during CPR and, additionally, to evaluate the effects of intraosseous vasopressin during CPR. DESIGN: Prospective, randomized laboratory investigation using an established porcine model with instrumentation for measurement of hemodynamic variables, blood gases, and return of spontaneous circulation. SETTING: University hospital laboratory. SUBJECTS: Twelve domestic pigs. INTERVENTIONS: After 4 mins of untreated ventricular fibrillation and 3 mins of CPR, 12 pigs were randomized to be treated with intravenous administration of vasopressin (0.8 unit/kg vasopressin; n = 6) or intraosseous vasopressin (0.8 unit/kg vasopressin; n = 6). Defibrillation was performed 5 mins after drug administration to attempt the return of spontaneous circulation. MEASUREMENTS AND MAIN RESULTS: At both 90 secs and 5 mins after drug administration, intravenous and intraosseous administration of vasopressin resulted in comparable mean (+/-SEM) coronary perfusion pressure (43+/-4 vs. 44+/-3 and 30+/-2 vs. 37+/-2 mm Hg, respectively) and vasopressin plasma concentrations (13,706+/-1,857 vs. 16,166+/-3,114 pg/mL and 10,372+/-883 vs. 8246+/-2211 pg/mL, respectively). All animals in both groups were successfully resuscitated; pigs that received intraosseous vasopressin had a significantly higher (p < .05) mean arterial (92+/-6 vs. 129+/-12 mm Hg) and coronary perfusion pressure (84+/-11 vs. 119+/-11 mm Hg) at 5 mins of return of spontaneous circulation. CONCLUSIONS: Intraosseous vasopressin resulted in comparable vasopressin plasma levels, hemodynamic variables, and return of spontaneous circulation rates as did intravenous vasopressin. Intraosseous vasopressin may be an alternative for vasopressor administration during CPR, when intravenous access is delayed or not available.     

Tissue factor over-expression by human pancreatic cancer cells BXPC3 is related to higher prothrombotic potential as compared to breast cancer cells MCF7

Cancer histology influences the risk of venous thromboembolism and tissue factor (TF) is the key molecule in cancer-induced hypercoagulability. We investigated the relation between TF expression by pancreatic and breast cancer cells (BXPC3 and MCF7 respectively) and their capacity to trigger in vitro thrombin generation in normal human plasma. Flow cytometry and Western blot analysis for TF expression were performed using murine IgG1 monoclonal antibody against human TF. Real-time PCR for TFmRNA was also performed. Activity of TF expressed by cancer cells was measured with a specific chromogenic assay. Thrombin generation in PPP was assessed using calibrated automated thrombogram. Cancer cells were added to platelet poor plasma from healthy volunteers. In separate experiments cells were incubated with the anti-TF antibody at concentration that completely neutralized the activity of recombinant human TF on thrombin generation. BXPC3 cells expressed significantly higher amounts of functional TF as compared to MCF7 cells. Incubation of BXPC3 and MCF7 cells with PPP resulted in acceleration of the initiation phase of thrombin generation. BXPC3 cells manifested higher procoagulant potential than MCF7 cells. The incubation of BXPC3 or MCF7 cells with the anti-TF monoclonal antibody which resulted in reversal of their effect on thrombin generation.The present study establishes a link between the amount of TF expressed by cancer cells with their procoagulant activity. Both studied types of cancer cells trigger thrombin generation but they have different procoagulant potential. The procoagulant activity of BXPC3 and MCF7 cells is related to the amount of TF expressed. Kinetic parameters of thrombogram are the most relevant for the detection of the TF-dependent procoagulant activity of cancer cells. TF expression is one of the mechanisms by which cancer cells manifest their procoagulant potential but it is not the unique one. The present experimental model will allow the characterization the procoagulant fingerprint of cell lines from the same or different histological types of cancer.     

Effect of phased chest and abdominal compression-decompression cardiopulmonary resuscitation on myocardial and cerebral blood flow in pigs

OBJECTIVE: This study was designed to assess the effects of a phased chest and abdominal compression-decompression cardiopulmonary resuscitation (CPR) device, Lifestick, vs. standard CPR on vital organ blood flow in a porcine CPR model. DESIGN: Prospective, randomized laboratory investigation using an established porcine model with instrumentation for measurement of hemodynamic variables, vital organ blood flow, blood gases, and return of spontaneous circulation. SETTING: University hospital research laboratory. SUBJECTS: Twelve domestic pigs. INTERVENTIONS: After 4 mins of untreated ventricular fibrillation, either the Lifestick CPR device (n = 6) or standard CPR (n = 6) was started and maintained for an additional interval of 6 mins before attempting defibrillation. MEASUREMENTS AND MAIN RESULTS: During CPR, but before epinephrine, use of the Lifestick CPR device resulted in significantly higher (p < .05) mean (+/- SD) coronary perfusion pressure (23+/-9 vs. 10+/-7 mm Hg), cerebral perfusion pressure (29+/-11 vs. 18+/-10 mm Hg), mean arterial pressure (49+/-10 vs. 36+/-13 mm Hg), end-tidal carbon dioxide (32+/-11 vs. 20+/-7 mm Hg), left ventricular myocardial blood flow (44+/-19 vs. 19+/-12 mL x min(-1) x 100 g(-1)), and total cerebral blood flow (29+/-10 vs. 14+/-12 mL x min(-1) x 100 g(-1)). After 45 microg/kg epinephrine, hemodynamic and vital organ blood flow variables increased to comparable levels in both groups. CONCLUSIONS: Compared with standard CPR, the Lifestick CPR device increased significantly hemodynamic variables and vital organ blood flow during CPR before epinephrine administration.     

Effects of tranylcypromine on thyroid hormone metabolism and concentrations in rat brain

The effect of 14 days administration of the anti-depressant tranylcypromine (TCP) on iodothyronine deiodinase activities and the concentrations of thyroxine (T4) and triiodothyronine (T3) were investigated in homogenates of up to nine regions of the rat brain. The activity of the 5III deiodinase isoenzyme, which catalyses the inactivation of T3 to 3,3'-diiodothyronine (3,3'-T2), was enhanced in eight brain regions. However, the brain levels of T4 were completely unchanged and the T3 concentrations were significantly reduced in the frontal cortex only. Therefore, we also measured the T3 concentrations of three subcellular fractions (nuclei, synaptosomes and mitochondria) of six brain regions. TCP induced a significant reduction in T3 levels in the synaptosomes of the frontal cortex and significant increases in the mitochondrial T3 concentrations in the amygdala. The latter effect was replicated after 14 days administration of 5 mg/kg desipramine. No effects of either drug on nuclear concentrations of T3 were seen in any brain region. As the amygdala is critically involved in the affective coloring of sensory stimuli, the increase in T3 concentrations in the mitochondria of this brain region may be of relevance for the mechanism of action of anti-depressant drugs.     

Influence of epinephrine on systemic, myocardial, and cerebral acid-base status during cardiopulmonary resuscitation

During cardiopulmonary resuscitation (CPR), arterial pH and carbon dioxide tension (PCO2) do not reflect the marked acidosis and hypercapnia seen in venous blood samples during CPR. Epinephrine causes an increase in myocardial and cerebral blood flow during CPR, but the influence on regional venous PCO2 and pH is as yet unknown. Fourteen pigs were allocated to receive either 0.9% saline (n = 7), or 45 micrograms/kg epinephrine (n = 7) after 5 min of ventricular fibrillation and 3 min of open-chest CPR. Blood samples were obtained during CPR from the aorta, pulmonary artery, great cardiac vein, and sagittal sinus before and 90 s and 5 min after drug administration. Regional blood flow was measured with tracer microspheres. Plasma catecholamines were quantified by high-performance liquid chromatography in arterial blood. PCO2 90 s after drug administration in arterial, mixed venous, myocardial venous, and cerebral venous blood were (means +/- SD) 36 +/- 8, 67 +/- 9, 74 +/- 14, and 79 +/- 19 mmHg in the control group and 35 +/- 11, 62 +/- 12, 73 +/- 10, and 71 +/- 14 mmHg in the epinephrine group. pH values 90 s after drug administration in the same blood samples were 7.29 +/- 0.11, 7.11 +/- 0.09, 7.04 +/- 0.09, and 7.07 +/- 0.10 in the control group and 7.31 +/- 0.13, 7.17 +/- 0.07, 7.08 +/- 0.08, and 7.07 +/- 0.12 in the epinephrine group. Despite a significant increase in myocardial and cerebral blood flow after epinephrine, PCO2 and pH in all blood samples were not different from those of the control group. (ABSTRACT TRUNCATED AT 250 WORDS)     

Comparison of standard and high-dose adrenaline in the resuscitation of asystole and electromechanical dissociation

Sixty-eight adults with cardiac arrest (asystole and electromechanical dissociation) were randomly allocated for treatment with standard (1 mg) or high-dose epinephrine (5 mg). If the first dose of adrenaline (1 or 5 mg) failed, standardized advanced life-support was applied in all cases. High-dose adrenaline was associated with higher initial resuscitation success rates (16 of 28) than standard-dose adrenaline (6 of 40), whereas hospital discharge rates were not significantly different between the groups. Blood pressure was significantly higher in the high-dose adrenaline group in comparison to the standard dose at 1 and 5 min after resuscitation. Although high-dose adrenaline appears to improve cardiac resuscitation success, the duration of global cerebral ischaemia seems to determine the ultimate outcome.