Temperature-dependent formation of a conjugate between tris(hydroxymethyl)aminomethane buffer and the malondialdehyde-DNA adduct pyrimidopurinone

OBJECTIVE: To examine the effects of cardiopulmonary bypass (CPB) on total and unbound plasma concentrations of propofol and midazolam when administered by continuous infusion during cardiac surgery. DESIGN: Prospective clinical study. SETTING: University hospital. PARTICIPANTS: Twenty-four adult patients undergoing cardiac surgery. INTERVENTIONS: Patients received either propofol or midazolam to supplement fentanyl anesthesia. Twelve patients received a propofol bolus (1 mg/kg) followed by an infusion of 3 mg/kg/hr. A second group received midazolam, 0.2 mg/kg bolus, followed by an infusion of 0.07 mg/kg/hr. MEASUREMENTS AND MAIN RESULTS: Blood sample were collected from the radial artery cannula at 0, 2, 4, 8, 8, 10, 15, 20 minutes and then every 10 minutes before CPB, at 1, 2, 3, 4, 6, 10, 15, 20 minutes and then each 10 minutes during CPB. On weaning from CPB samples were collected at 0, 5, 10 and 20 minutes. Plasma binding, total and unbound propofol and midazolam concentrations were determined by ultrafiltration and high-pressure liquid chromatography (HPLC). CPB resulted in a fall in total propofol and midazolam plasma concentrations, but the unbound concentrations remained stable. The propofol unbound fraction increased from 0.22 +/- 0.06% to 0.41 +/- 0.17%. The midazolam unbound fraction increased from 5.6 +/- 1.0% to 11.2 +/- 2.1%. CONCLUSIONS: Unbound concentrations of propofol and midazolam are not affected by cardiopulmonary bypass. Total intravenous anesthesia algorithms do not need to be changed to achieve stable unbound plasma concentrations when initiating CPB.     

The effects of propofol, isoflurane, and sevoflurane on oxygenation and shunt fraction during one-lung ventilation

Propofol's effect on hypoxic pulmonary vasoconstriction during one-lung ventilation (OLV) has not been determined. Twenty patients who had long-term OLV for esophageal surgery were allocated randomly to one of two study groups; one in which isoflurane administration preceded propofol, and another in which sevoflurane administration preceded propofol. Arterial and mixed venous blood samples and hemodynamics were measured as follows: before OLV, during OLV, OLV at 4 cm of positive end-expiratory pressure (PEEP), OLV after conversion from volatile anesthetics to propofol, OLV at 4 cm of PEEP, and after OLV. After the application of 4 cm of PEEP during propofol anesthesia, PaO2 increased significantly in both groups. The shunt fraction (Qs/Qt) increased significantly after the initiation of OLV in both groups and decreased significantly after the conversion from volatile anesthetics to propofol in both groups. Propofol can be used safely during OLV because PaO2 increased after the application of 4 cm of PEEP during propofol anesthesia, and Qs/Qt decreased significantly after the conversion from inhaled anesthetics to propofol anesthesia. IMPLICATIONS: During one-lung ventilation, the arterial partial pressure of oxygen values with propofol were greater than those with isoflurane and sevoflurane, and shunt fraction values with propofol were lower than those with both volatile anesthetics. Propofol improved oxygenation and shunt fraction during one-lung ventilation compared with volatile anesthetics.     

Post-laparoscopic vomiting in females versus males: comparison of prophylactic antiemetic action of ondansetron versus metoclopramide

PURPOSE: To evaluate the clinical usefulness of the continuous intra-arterial blood gas (CIABG) monitoring system, Paratrend 7, during differential lung ventilation (DLV) in 12 patients undergoing oesophagectomy. METHODS: Anaesthesia was induced with propofol and was maintained with isoflurane, oxygen and air, supplemented by an epidural infusion of mepivacaine. Arterial samples for estimation of blood gases (ABG) were taken just before and 5, 10, 20, 30, 60, and 90 min after the pleura was opened. The pH, PO2, and PCO2 values displayed by the CIABG monitor, which were recorded prior to the arterial blood sampling, were compared with the results of ABG analysis. RESULTS: Eighty-four blood samples were obtained and the ranges for the measured variables were PCO2 24.8-57.4 mmHg, PO2 47-449 mmHg, and pH 7.30-7.49. The correlation between CIABG and ABG measurements was strong and significant (r values: PCO2 0.80, PO2 0.93, pH 0.94). The overall bias +/- precision between the two methods was PCO2 0.9 +/- 3.1 mmHg, PO2 -1 +/- 40 mmHg, %PO2 0.8 +/- 21.6%, pH 0.00 +/- 0.02. For PO2 values < 150 mmHg, the biases +/- precision were PO2 -5 +/- 17 mmHg, %PO2 -2.1 +/- 20.7%. CONCLUSION: The agreement between CIABG and ABG measurements was better for PCO2 and pH than for PO2. Although the CIABG system is clinically useful for monitoring trends in blood gas changes, the accuracy of the PO2 value may be unacceptable during DLV because the error is theoretically < 34 mmHg with 95% reliability in the clinically important range of PO2, < 150 mmHg.     

Effect of thoracic epidural anaesthesia on ventilation-perfusion distribution and intrathoracic blood volume before and after induction of general anaesthesia

BACKGROUND: Gas exchange is impaired during general anaesthesia due to development of shunt and ventilation-perfusion mismatching. Thoracic epidural anaesthesia (TEA) may affect the mechanics of the respiratory system, intrathoracic blood volume and possibly ventilation-perfusion (VA/Q) distribution during general anaesthesia. METHODS: VA/Q relationships were analyzed in 24 patients undergoing major abdominal surgery. Intrapulmonary shunt (Qs/QT), perfusion of "low" VA/Q areas, ventilation of "high" VA/Q regions, dead space ventilation and mean distribution of ventilation and perfusion were calculated from the retention/excretion data of six inert gases. Intrathoracic blood volume (ITBV) and pulmonary blood volume (PBV) were determined with a double indicator technique. Recordings were made before and after administration of 8.5 +/- 1.5 ml bupivacaine 0.5% (n = 12) or 8.3 +/- 1.8 ml placebo (n = 12) into a thoracic epidural catheter and after induction of general anaesthesia. RESULTS: Before TEA, Qs/QT was normal in the bupivacaine group (2 +/- 2%) and the placebo group (2 +/- 3%). TEA covering the dermatomal segments T 12 to T 4 had no effect on VA/Q relationships, ITBV and PBV. After induction of general anaesthesia Qs/QT increased to 8 +/- 4% (bupivacaine group, P < 0.05 and to 7 +/- 2% (placebo group, P < 0.05). ITBV and PBV decreased significantly to the same extent in the bupivacaine group and the placebo group. CONCLUSIONS: TEA has no effect on VA/Q distribution, gas exchange and intrathoracic blood volume in the awake state and does not influence development of Qs/QT and VA/Q inequality after induction of general anaesthesia.     

Influence of dopamine on the pulmonary pressure and shunt volume after cardiac surgery (author's transl)

After the administration of Dopamine to 20 patients after cardiac surgery pulmonary shunt volume was determined with regard to the cardiac output and pulmonary pressure. It was shown that the infusion of Dopamine leads to decrease of the arterio-venous oxygen difference (AVDO2) as well as to the decrease of the PO2 in the arterial blood. On the contrary, in venous bood, PO2, Oxygen saturation, content and pulmonary pressure increased. The increase of the pulmonary right-to-left shunt observed (Qs Qt form 14.9 to 19.2%) is in proportion with the increase in cardiac output. Hence we do not suppose a specific shunting effect of Dopamine. Our findings suggest, that in the case of an already reduced blood oxygen level a further fall of the arterial oxygen saturation caused by a shunt must be avoided by additional enrichment of oxygen content of the inspired air.     

Paraneoplastic and oncologic profiles of patients seropositive for type 1 antineuronal nuclear autoantibodies

The association of propofol with excitatory motor activity, such as myoclonic jerking and opisthotonus, in humans and in animals suggests that it may aggravate clinical seizure activity in some circumstances, although evidence suggests that under other circumstances, propofol inhibits seizure activity. In the current study, we assessed the effect of sedating doses of propofol on lidocaine-induced seizure activity in spontaneously breathing rats receiving no other anesthetics. Adult Sprague-Dawley male rats, 300-400 g, were divided into a control group and three experimental groups representing three graded levels of propofol sedation. The control rats then received a lidocaine infusion at the rate of 150 mg x kg(-1) x h(-1), resulting in a slow, progressive increase in systemic lidocaine concentrations. At the onset of electroencephalographic (EEG) seizure activity, arterial lidocaine concentrations were obtained. The treated rats received propofol according to three different dose schedules: Dose 1 = 10 mg x kg(-1) x h(-1) after a 2.5-mg/kg bolus; Dose 2 = 20 mg x kg(-1) x h(-1) after a 5-mg/kg bolus; Dose 3 = 40 mg x kg(-1) x h(-1) after a 10-mg/kg bolus. After 30 min, a steady level of sedation, dependent on the dose of propofol, was achieved. The lidocaine infusion was then started, and systemic lidocaine levels were obtained at the onset of EEG seizure activity. The lidocaine was continued until the onset of death by cardiac arrest. Plasma lidocaine was measured by gas chromatography. Analysis of variance and Dunnett's t-test were used for comparisons with the control values. Continuous propofol sedation increased the seizure dose of lidocaine from 37.7 +/- 3.5 mg/kg (mean +/- SEM) to 52.5 +/- 2.6 mg/kg (Dose 1, P < 0.05) and 67.9 +/- 8.6 mg/kg (Dose 2, P < 0.05), and completely abolished lidocaine seizures at Dose 3. The lethal dose of lidocaine, 89.4 +/- 10.5 mg/kg control versus 108.7 +/- 10.3 mg/kg (Dose 1), 98.3 +/- 10.1 mg/kg (Dose 2), and 93.5 +/- 10.4 mg/kg (Dose 3) did not differ among groups. The lidocaine levels at seizure threshold were increased in the propofol-treated rats: 16.9 +/- 0.5 microg/mL control versus 19.2 +/- 0.7 microg/mL (Dose 1, P = not significant) and 23.7 +/- 1.8 microg/mL (Dose 2, P < 0.05). Continuous propofol sedation in spontaneously breathing rats receiving no other anesthetics exerts a protective effect against lidocaine-induced seizures in a monotonic, dose-dependent fashion. The cardiac arrest dose of lidocaine is unaffected by propofol under these conditions. IMPLICATIONS: The i.v. anesthetic drug propofol, given to rats to produce sedation, was found to suppress seizure activity caused by overdosage of the local anesthetic lidocaine.     

Respiratory toxicity of direct lytic factor in the venom of the southern Chinese cobra (N. naja atra) in dogs

The effects of direct lytic factor (DLF) on respiratory ventilation, gas exchange as well as hemodynamics were studied in anesthetized dogs. After an intravenous DLF dose of 1 mg/kg, the initial manifestation of intoxication was observed as follows: (1) Increase in airway impedance characterized by slowed air flow rate and increased negative transpulmonary pressure. (2) Decrease in dynamic compliance. (3) Progressive increase in venoarterial shunt (Qs/Qt) and decrease in PaO2, (4) Elevation of pulmonary artery blood pressure and fall of mean systemic blood pressure and maximal left ventricular pressure. Above actions reached the peak values at 15 min and thereafter all respiratory functional parameters, except Qs/Qt and hypoxemia, returned gradually to approach the normal levels at 50 min. The tidal volume, PaCO2 and LVEDP remained unchanged until another DLF dose of 1.5 mg/kg was given. After a second dose of DLF (total 2.5 mg/kg), the respiratory functions and the cardiac performance deteriorated as follows: (1) Further increase in Qs/Qt and hypoxemia. (2) Appearance of hypercapnea and acidosis. (3) Fall of dP/dtmax and elevation of LVEDP, widening of QRS complex of ECG. (4) Blood pressure run a downhill course. From above experimental evidence, we came to the conclusion that as well as the basic cardiotoxicity, respiratory toxicity of DLF must be considered as the primary, because of broad spectrum of action of DLF and early effect on respiratory function.     

Helicobacter pylori eradication in the healing and recurrence of benign gastric ulcer: a two-year, double-blind, placebo controlled study

STUDY OBJECTIVE: To evaluate the safety and efficacy of monitored anesthesia care (MAC) in patients who undergo a novel treatment for hepatocellular cancer in which procedure-related hemodynamic instability is problematic. DESIGN: Nonrandomized open study. SETTING: University cancer center operating room. PATIENTS: Nine patients scheduled for hepatic arterial infusion of doxorubicin with complete hepatic venous isolation and extracorporeal chemofiltration (no more than 3 procedures per patient). INTERVENTIONS: Hepatic venous isolation was achieved with a dual-balloon inferior vena cava catheter connected to an extracorporeal circuit containing chemofilters. Doxorubicin was infused through the hepatic artery and filtered from the venous blood, which was returned to the patient through an internal jugular venous catheter. Each patient received a bolus of propofol (200 micrograms/kg) and one of alfentanil (2 micrograms/kg) followed by simultaneous infusions of propofol and alfentanil for percutaneous placement of the catheters and operation of the extracorporeal circuit. Drug rates were varied to maintain a sedative-analgesic state of calm, comfort, minimal movement, and adequate respiratory function. Prior to circuit initiation, patients were preloaded with crystalloid. During circuit operation, hypotension was treated with intravenous (IV) phenylephrine and crystalloid. MEASUREMENTS AND MAIN RESULTS: End-tidal CO2 (PETCO2), respiratory rate, oxygen saturation (SaO2), arterial blood pressure (BP), and heart rate (HR) were monitored. Systolic, diastolic, and mean arterial pressure (MAP), and HR were compared before, during, and after hepatic venous isolation and chemofiltration. Doses and infusion rates of propofol, alfentanil, and phenylephrine were recorded for each treatment. Hypotension occurred in 11 of 13 procedures when blood was directed through the chemofilters and was successfully treated with phenylephrine (dose range 40 to 5,733 micrograms) and crystalloid. Blood pressure returned to the baseline value on termination of the circuit. Throughout the sedation, patients were easily arousable, analgesia was adequate, and PETCO2 level of 38 +/- 4 mmHg and SaO2 greater than 94% were maintained. Mean doses and infusion rates of MAC drugs were, respectively: propofol, 261 +/- 88 mg and 23.7 +/- 3.6 micrograms/kg/min; alfentanil, 3,350 +/- 1,468 micrograms and 0.32 +/- 0.14 microgram/kg/min. CONCLUSIONS: Patients undergoing this novel cancer treatment are safely and effectively managed by MAC achieved with simultaneous infusions of alfentanil and propofol. Procedure-associated hypotension is easily treated with IV phenylephrine and crystalloid.     

Physiological dead space/tidal volume ratio during face mask, laryngeal mask, and cuffed oropharyngeal airway spontaneous ventilation

OBJECTIVE: To compare the physiological dead space/tidal volume ratio and arterial to end-tidal carbon dioxide tension (ETCO2) difference during spontaneous ventilation through a face mask, a laryngeal mask (LMA), or a cuffed oropharyngeal airway. DESIGN: Prospective, randomized, cross-over study. SETTING: Inpatient anesthesia at a university department of orthopedic surgery. PATIENTS: 20 ASA physical status I and II patients, without respiratory disease, who underwent ankle and foot surgery. INTERVENTIONS: After a peripheral nerve block was performed, propofol anesthesia was induced and then maintained with a continuous intravenous (i.v.) infusion (4 to 6 mg/kg/h). A face mask, a cuffed oropharyngeal airway, or an LMA were placed in each patient in a random sequence. After 15 minutes of spontaneous breathing through each of the airways, ventilatory variables, as well as arterial, end-tidal, and mixed expired CO2 partial pressure, were measured, and physiological dead space/tidal volume ratio was calculated. MEASUREMENTS AND MAIN RESULTS: Expired minute volume and respiratory rate (RR) were lower with LMA (5.6 +/- 1.2 L/min and 18 +/- 3 breaths/min) and the cuffed oropharyngeal airway (5.7 +/- 1 L/min and 18 +/- 3 breaths/min) than the face mask (7.1 +/- 0.9 L/min and 21 +/- 3 breaths/min) (p = 0.0002 and p = 0.013, respectively). Physiological dead space/tidal volume ratio and arterial to end tidal CO2 tension difference were similar with the cuffed oropharyngeal airway (3 +/- 0.4 mmHg and 4.4 +/- 1.4 mmHg) and LMA (3 +/- 0.6 mmHg and 3.7 +/- 1 mmHg) and lower than with the face mask (4 +/- 0.5 mmHg and 6.7 +/- 2 mmHg) (p = 0.0001 and p = 0.001, respectively). CONCLUSION: Because of the increased dead space/tidal volume ratio, breathing through a face mask required higher RR and expired minute volume than either the cuffed oropharyngeal airway or LMA, which, in contrast, showed similar effects on the quality of ventilation in spontaneously breathing anesthetized patients.     

Hemodynamic effects of epinephrine, bicarbonate and calcium in the early postnatal period in a lamb model of single-ventricle physiology created in utero

OBJECTIVES: A reproducible fetal animal model of single-ventricle physiology was created to examine the effects of pharmacologic agents commonly used in the perinatal and perioperative intensive care management of patients with a single ventricle. BACKGROUND: Single-ventricle physiology is characterized by parallel pulmonary and systemic circulations, with effective blood flow to each determined by the relative resistances in the pulmonary and systemic vascular beds. Perinatal and perioperative management of these patients is largely based on empiric observations and differs considerably between institutions and is further complicated by the transitional physiology of the newborn. The lack of animal models of single-ventricle physiology has hindered the understanding of this problem. METHODS: A 10-mm, Damus-Kaye-Stansel-type aortopulmonary anastomosis was created in 10 fetal sheep at 140 +/- 1.2 days of gestation. The main pulmonary artery was ligated distally, and pulmonary blood flow (Qp) was provided through a 5-mm aortopulmonary shunt. Eight lambs were delivered at term and placed on cardiopulmonary bypass (30 min) 48 to 72 h after birth. Pharmacologic interventions (0.1 microgram/kg body weight per min of epinephrine, 2 mEq/kg of sodium bicarbonate and 10 mg/kg of calcium chloride) were performed before and after bypass, and hemodynamic responses were observed. The response to the epinephrine bolus was determined only in the postbypass study. RESULTS: Both before and after bypass, epinephrine infusion and calcium and bicarbonate administration increased Qp and systemic blood flow (Qs) (total cardiac output) but produced only small changes in the Qp/Qs ratio (-0.5% to -7.3% change). With the epinephrine bolus, Qp increased enormously, and the Qp/Qs ratio increased by 584% (p < 0.001). CONCLUSIONS: In neonatal lambs with single-ventricle physiology created in utero, epinephrine infusion and calcium and bicarbonate administration increased total cardiac output without significantly compromising the Qp/Qs ratio. However, epinephrine bolus seems to be hemodynamically detrimental in circumstances of single-ventricle physiology and should be used with caution and probably in relatively lower doses in the resuscitation of patients with single-ventricle physiology. Further investigation of the dose-dependent effects and the effects of prolonged administration of common pharmacologic agents will enable better management of patients with single-ventricle physiology.     

Relationship between auditory intensity discrimination in noise and olivocochlear efferent system activity in humans

The intravenous (i.v.) steroid anesthetic, eltanolone, compares favorably to propofol with respect to its induction characteristics. This double-blind investigation was designed to compare the induction and recovery profile of eltanolone (versus propofol) when it was used for both induction and maintenance of ambulatory anesthesia. Eighty-three consenting ASA physical status I-III outpatients undergoing minor gynecologic or urologic procedures lasting 10-40 min were randomly assigned to one of three anesthetic treatment groups. All patients received midazolam, 2 mg i.v., and fentanyl, 50 micrograms i.v., before induction of anesthesia. The control group (Group 1) was induced with propofol, 2.4 mg/kg i.v. (18-60 yr or ASA physical status I or II) or 1.6 mg/kg i.v. (61-80 yr and/or ASA physical status III), followed by intermittent bolus doses of 0.6 mg/kg i.v. in combination with N2O 67% for maintenance of anesthesia. In Group 2, anesthesia was induced with eltanolone, 0.75 mg/kg i.v., (18-60 yr and/or ASA physical status I or II) or 0.5 mg/kg i.v. (61-80 yr and/or ASA physical status III), and maintained with intermittent bolus injections of 0.2 mg/kg i.v. and N2O 67%. Group 3 received eltanolone, 1.0 mg/kg i.v. (18-60 yr and/or ASA physical status I or II), or 0.75 mg/kg i.v. (61-80 yr and/or ASA physical status III), followed by intermittent bolus injections of 0.2 mg/kg i.v. and N2O 67%. In addition to recording the induction and recovery times and side effects, psychomotor testing was performed before and at 30-min intervals after anesthesia. Induction times (57 +/- 23, 67 +/- 26, and 61 +/- 22s, respectively) were similar in all three groups. Although eltanolone produced no pain on injection (versus 52% in the propofol group), 10% of the eltanolone-treated patients (versus none in the propofol group) developed transient cutaneous (rash-like) reactions. The total dose of study medication used during the anesthetic period was 9.2 +/- 3.7 mg.kg-1.h-1 in the propofol group compared with 3.3 +/- 1.4 mg.kg-1.h-1 and 3.3 +/- 1.9 mg.kg-1.h-1 in Groups 2 and 3, respectively. Early recovery times were significantly shorter after propofol anesthesia. However, times to ambulation, micturition, and being judged "fit for discharge," as well as recovery of cognitive function, were similar in all three groups. Although ethanolone seems to be a safe and effective i.v. anesthetic, these data suggest that it is unlikely to replace propofol in the ambulatory setting. Implications: Eltanolone is an investigational steroid anesthetic that causes less pain on injection and less cardiovascular depression than propofol (the most widely used intravenous anesthetic in the outpatient setting). Unfortunately, emergence from anesthesia after ambulatory surgery is slower with eltanolone compared with propofol. Therefore, it is unlikely that eltanolone will replace propofol for outpatient anesthesia.     

Hepatocyte nuclear factor-4 alpha gene mutations in Japanese non-insulin dependent diabetes mellitus (NIDDM) patients

OBJECTIVE: To assess the effect of pregnancy, maternal position, and cardiac output on intrapulmonary shunting (Qs/Qt) in normotensive nulliparous women near term. METHODS: Ten normotensive nulliparas between 36 and 38 weeks' gestation underwent pulmonary artery catheterization (via the subclavian route) and radial artery canalization. Baseline assessments were made with subjects in the left lateral recumbent position after a 30-minute stabilization period. Measurements were obtained sequentially in the left lateral, right lateral, supine, knee-chest, sitting, and standing positions. Each position change was followed by a 10-minute pre-measurement stabilization period. Cardiac output was measured via the thermodilution technique. Blood samples were obtained simultaneously from the pulmonary and radial arteries and analyzed in duplicate for oxygen content with a blood gas analyzer. Qs/Qt was calculated using the classic shunt equation. Statistical analysis was performed by analysis of variance of repeated measures of Qs/Qt and maternal position. The relationship of Qs/Qt to maternal cardiac output was evaluated by the correlation coefficient. Significance was defined as P < .05. RESULTS: Directly measured Qs/Qt averaged 15.3% in left lateral, 15.2% in right lateral, 13.9% in supine, 12.8% in knee-chest, 13.8% in sitting, and 13.0% in standing positions. There was no statistically significant correlation between Qs/Qt and cardiac output (R2 = 0.11, not significant). CONCLUSION: This is the first report of directly measured Qs/Qt in normal pregnant women in the third trimester. Qs/Qt values reported in pregnancy are higher than those reported in nonpregnant individuals.     

Involvement of osmo-sensitive calcium influx in human sperm activation

OBJECTIVE: To compare the efficacy of Yagin, a factor Xa inhibitor derived from the leech Hirudo medicinalis, with those of heparin and hirudin as adjuncts to recombinant tissue-type plasminogen activator (rTPA) thrombolysis in a rabbit thrombosis model. METHODS: Thirty-one animals were allocated randomly to three groups, all administered four boluses of 0.25 mg/kg rTPA every 10 min for 30 min, 17 mg/kg aspirin intravenously, and heparin (as a 100 IU/kg bolus followed by infusion of 50 IU/kg heparin per h), hirudin (as a 2 mg/kg bolus followed by infusion of 1 mg/kg hirudin per h), or Yagin (as an 80 micrograms/kg bolus followed by infusion of 43 micrograms/kg Yagin per h). RESULTS: Administration of Yagin was associated with a significant acceleration of the reflow time, this time being 14.5 +/- 1.2 min with Yagin, 25.8 +/- 5.2 min with heparin (P < 0.0001, versus Yagin), and 28.7 +/- 16.0 min with hirudin (P = 0.012, versus Yagin). Overall patency did not differ significantly among the three groups. CONCLUSIONS: At the indicated single doses, inhibition of factor Xa by a relatively low concentration of Yagin was found to be superior than that with either heparin or hirudin for accelerating rTPA thrombolysis.     

Use of Diprivan in radiology

For radiological examinations, propofol is administered, depending on the indications, at following doses: for anxiolysis: i.v. bolus of 10-20 mg, repeated as required; for sedation with maintenance of spontaneous ventilation: i.v. bolus of 0.5 mg.kg-1 or continuous infusion of 3 mg.kg.h-1. for general anaesthesia: i.v. bolus of 2 mg.kg-1 and maintenance with a continuous infusion of 6-10 mg.kg-1.h-1. These doses are modified according to the patient's reactions and painful episodes. In neuroradiology, indications for anaesthesia include vascular explorations, MRI, computerized axial tomography, as well as biopsies of organs and tumors, with the exception of explorations in patients with tight stenoses of the carotid artery. The use of propofol for cardiological explorations is questioned in adults and mainly in children with a congenital cardiopathy. For some authors this agent is contra-indicated, as during induction it decreases, sometimes excessively, the mean arterial pressure.     

Comparison of eltanolone and propofol in anesthesia for termination of pregnancy

A randomized study was designed to compare eltanolone (pregnanolone) and propofol anesthesia in 60 unpremedicated women undergoing outpatient termination of pregnancy. The initial doses for induction of anesthesia were 0.8 mg/kg for eltanolone and 2 mg/kg for propofol followed by an additional 25% increment if necessary. The doses required for successful induction were 0.82 +/- 0.06 and 2.1 +/- 0.3 (mean +/- SD) mg/kg for eltanolone and propofol, respectively. Discomfort or pain on injection occurred in none of the patients given eltanolone and in 20% of those receiving propofol (P < 0.05). To maintain satisfactory anesthesia, 29% of the patients given eltanolone and 70% of the patients given propofol needed extra bolus doses of the study drug (P < 0.01). Excitation (twitching of extremities or slight hypertonus) occurred in 29% of the patients in the eltanolone group compared to none in the propofol group (P < 0.05). Both clinical (opening eyes, orientation, walking, tolerating oral fluids, voiding) and psychomotor recovery (Maddox Wing test and Digit Symbol Substitution test) returned to baseline more slowly after eltanolone than after propofol. Overall home readiness was achieved later in the eltanolone group [median 57 min (range 41-190 min)] compared to the propofol [37 (32-100 min)] group. We conclude that recovery from anesthesia is more rapid from propofol as compared to eltanolone anesthesia.     

Effect of remifentanil on clinical and electroencephalographic parameters of depth of anesthesia in balanced anesthesia with propofol, enflurane or isoflurane

Electrophysiological parameters are well-suited to detect changes in cerebral function. The present study investigates whether balanced anaesthesia with remifentanil during nociceptive stimulation is associated with changes in clinical and electrophysiological parameters indicating inadequate depth of anaesthesia. Following IRB approval and written informed consent, 23 patients (ASA: I; age: 36 +/- 11) scheduled for elective gynaecological laparoscopy were included in the study. Without any premedication, anaesthesia was induced with remifentanil (1.0 microgram/kg bolus injection), propofol (0.5 mg/kg added by repetitive (10 mg) bolus injections every 10 s until unconciousness) and vecuronium (0.1 mg/kg). Following endotracheal intubation (normoventilation: PetCO2: 36 bis 38 mmHg), remifentanil infusion was started with continuous doses of 0.5 microgram/kg/min over 5 minutes and maintained with 0.25 microgram/kg/min during surgery. Remifentanil was randomly combined with propofol (group 1: 100 micrograms/kg/min; n = 7), enflurane (group 2: 0.5 MAC; n = 8) or isoflurane (group 3: 0.5 MAC; n = 8). Monitoring included: heart rate (beats/min), mean arterial pressure (mmHg), oxygen saturation (%), endtidal CO2 (mmHg) and endtidal enflurane and isoflurane (%). EEG: 2-channel recordings of Fz versus mastoid and ECG (artefact control) during steady-state anaesthesia and surgery. Following fast-fourier-transformation (4 s; 256/s; 0.5 to 35.0 Hz), spectral power densities were calculated for the selected frequency bands. Auditory evoked potentials (AEP; middle latency) were registered simultaneously after binaural stimulation via head-phones click-stimulation (6 Hz; 75 dB above hearing threshold; 512 stimulations per average). Bandpass was 0.01 to 2.0 kHz. Analysis: Na, Pa, Nb (latencies; ms) and peak-to-peak amplitudes (NaPa, PaNb; microV). EEG and AEP recording technique [15]. The study protocol included baseline values from pre-intubation, pre-surgery, the respective post-stimulation values (1 min, 3 min, 5 min) and all data at five-minute intervals during surgery until emergence from anaesthesia. During steady-state study conditions with defined remifentanil applications, mean data indicate that in response to nociceptive stimuli no changes in clinical or electrophysiological parameters were observed. In contrast to other studies using different anaesthetic techniques, the present data from remifentanil indicate very stable haemodynamic and electrophysiological parameters (EEG, AEP) during noxious stimulations. Adjustable and with no plasma accumulation, remifentanil demonstrates potent antinociceptive effects resulting in signs of adequate anaesthesia.     

cAMP analogues downregulate the expression of granulocyte macrophage colony-stimulating factor (GM-CSF) in human bone marrow stromal cells in vitro

STUDY OBJECTIVE: To determine the neuromuscular blocking effect and recovery profile of cisatracurium besylate in children after administration of a bolus dose that was twice the estimated dose required to produce 95% of the maximum effect (2 x ED95; 0.08 mg/kg) followed by an infusion during halothane-nitrous oxide anesthesia. STUDY DESIGN: Open-label study. SETTING: Teaching hospital. PATIENTS: 30 male and female (ASA physical status I and II) patients, 2 to 10 years of age, scheduled for elective surgery of low to moderate risk. INTERVENTIONS: After induction of general anesthesia, patients received cisatracurium 0.08 mg/kg administered over 5 to 10 seconds. For surgical procedures requiring neuromuscular block for at least 60 minutes, a second bolus dose of cisatracurium 0.02 mg/kg was administered after the first response to a train-of-four stimuli (T1) recovered to 25% of baseline. When T1 was 5% of baseline after the second dose, a 3 microg/kg/min infusion of cisatracurium was initiated and titrated to maintain 89% to 99% block for the duration of the surgery. For procedures requiring neuromuscular block of less than 60 minutes, one or more maintenance doses of 0.02 mg/kg cisatracurium were administered when T1 was 25% of baseline after the preceding dose. In 10 patients, recovery was facilitated with edrophonium 1.0 mg/kg administered when T1 was 26% to 48% of the final baseline. MEASUREMENTS AND MAIN RESULTS: Evoked muscular response at the adductor pollicis was measured by electromyography. With 0.08 mg/kg, onset time (mean +/- SEM) was 4.1 +/- 0.4 minutes, and clinically effective duration was 27.3 +/- 0.9 minutes. Mean 5% to 95% and 25% to 75% recovery indices were 28.4 +/- 2. 7 minutes and 11.2 +/- 0.8 minutes, respectively. The mean infusion rate necessary to maintain 89% to 99% T1 suppression for 17 to 145 minutes was 1.7 microg/kg/min. After termination of infusion, the mean 5% to 95% and 25% to 75% recovery indices were similar to those after a single bolus dose, and time to 95% recovery was 30.4 +/- 3.0 minutes. After administration of edrophonium, full recovery (T4:T1 > or = 70%) occurred in 1.5 +/- 0.4 minutes. No clinically significant changes in heart rate or blood pressure were noted during the first 5 minutes after administration of cisatracurium 0.08 mg/kg. CONCLUSIONS: Cisatracurium provided maximal neuromuscular block, cardiovascular stability, and predictable recovery at the doses tested. In view of this finding, cisatracurium should be a useful intermediate-duration neuromuscular blocking drug for children during general anesthesia.     

Relation between impedance and electrode temperature during radiofrequency catheter ablation of accessory pathways and atrioventricular nodal reentrant tachycardia

OBJECTIVES: To evaluate and compare the clinical efficacy, impact on hemodynamics, safety profiles, and cost of combined administration of propofol and midazolam (synergistic sedation) vs. midazolam and propofol administered as sole agents, for sedation of mechanically ventilated patients after coronary artery bypass grafting. DESIGN: Prospective, controlled, randomized, double-blind clinical trial. SETTING: Intensive care unit of SCIAS-Hospital de Barcelona. PATIENTS: Seventy-five mechanically ventilated patients who underwent coronary artery bypass graft surgery under low-dose opioid anesthesia. INTERVENTIONS: According to the double-blind method, patients were randomly assigned to receive propofol (n = 25), midazolam (n = 25), or propofol combined with midazolam (n = 25). Infusion rates were adjusted to stay between 8 and 11 points on Glasgow Coma Score modified by Cook and Palma. MEASUREMENTS AND MAIN RESULTS: Mean +/- SD duration of sedation was 14.4 +/- 1.5 hrs, 14.1 +/- 1.1 hrs, and 14.7 +/- 1.9 hrs for the propofol, midazolam, and synergistic groups, respectively. The induction dose was 0.55 +/- 0.05 mg/kg for propofol as sole agent, 0.05 +/- 0.01 mg/kg for midazolam as sole agent, and 0.22 +/- 0.03 mg/kg for propofol administered in combination with 0.02 +/- 0.00 mg/kg of midazolam (p = .001). The maintenance dose was 1.20 +/- 0.03 mg/kg/hr for propofol as sole agent, 0.08 +/- 0.01 mg/kg/hr for midazolam as sole agent, and 0.50 +/- 0.09 mg/kg/hr for propofol administered in combination with 0.03 +/- 0.01 mg/kg/hr of midazolam (p < .001). All sedative regimens achieved similar efficacy in percentage of hours of adequate sedation (93% for propofol, 88% for midazolam, and 90% for the synergistic group, respectively). After induction, both propofol and midazolam groups had significant decreases in systolic blood pressure, diastolic blood pressure, left atrial pressure, and heart rate. Patients in the synergistic group had significant bradycardia throughout the study, without impairment in other hemodynamic parameters. Patients sedated with propofol or synergistic regimen awoke sooner and could be extubated before those patients sedated with midazolam (0.9 +/- 0.3 hrs and 1.2 +/- 0.6 hrs vs. 2.3 +/- 0.8 hrs, respectively, p = .01). Synergistic sedation produced cost savings of 28% with respect to midazolam and 68% with respect to propofol. CONCLUSIONS: In the study conditions, the new synergistic treatment with propofol and midazolam administered together is an effective and safe alternative for sedation, with some advantages over the conventional regimen with propofol or midazolam administered as sole agents, such as absence of hemodynamic impairment, >68% reduction in maintenance dose, and lower pharmaceutical cost.     

Ocular vascular thrombosis following tin ethyl etiopurpurin (SnET2) photodynamic therapy: time dependencies

In Germany a TCI-system for propofol (Disoprifusor-TCI) has been commercially available since spring 1997. We investigated the prediction error and precision of this TCI system as part of a multicentre study. Bias, precision, blood concentrations and dosage of propofol were compared with patients receiving propofol via a manually controlled infusion device. METHODS: After approval by the local Ethics Committee and written informed consent, 21 patients of ASA-classification I to III scheduled for major abdominal surgery received either a target controlled infusion (group T, Disoprifusor-TCI) or a manually controlled infusion (group M) of propofol. The propofol plasma concentrations were measured by HPLC. The prediction error for each measurement, the median prediction error (MDPE) or bias, the median absolute prediction error (MDAPE) or precision and the divergence (change of the prediction error over infusion time) were calculated for both groups. RESULTS: For all patients in group T (n = 12) the bias of the TCI system was 6.7% and the precision 27.5%. For 70% of all measured plasma concentrations the absolute prediction error was < or = 37%. The divergence was -5.4% per hour. For all patients in group M (n = 9) the bias was 44.2% and the precision 50%. The mean amount of propofol infused per kilogram body weight and hour was significant higher in T (9.0 +/- 1.2 mg/kg/h) than in M (6.6 +/- 1.2 mg/kg/h, p < 0.005). CONCLUSIONS: With a precision of 27.5% the investigated TCI system (Diprifusor-TCI) showed an acceptable inaccuracy, as for TCI-systems a median prediction error of +/- 30% has to be expected due to the inherent variability of pharmacokinetic parameters. Further studies will be necessary to find out whether the investigated TCI system for propofol may offer substantial advantages.     

Endocrine stress reaction, hemodynamics and recovery in total intravenous and inhalation anesthesia. Propofol versus isoflurane

This prospective, randomised study compared total intravenous anaesthesia (TIVA) and inhalation anaesthesia with respect to endocrine stress response, haemodynamic reactions, and recovery. METHODS. The investigation included two groups of 20 ASA I-II patients 18-60 years of age scheduled for orthopaedic surgery. For premedication of both groups, 0.1 mg/kg midazolam was injected IM. Patients in the propofol group received TIVA (CPPV, PEEP 5 mbar, air with oxygen FiO2 33%) with propofol (2 mg/kg for induction followed by an infusion of 12-6 mg/kg.h) and fentanyl (0.1 mg before intubation, total dose 0.005 mg/kg before surgery, repetition doses 0.1 mg). For induction of patients in the isoflurane-group, 5 mg/kg thiopentone and 0.1 mg fentanyl was administered. Inhalation anaesthesia was maintained with 1.2-2.4 vol.% isoflurane in nitrous oxide and oxygen at a ratio of 2:1 (CPPV, PEEP 5 mbar). For intubation of both groups, 2 mg vecuronium and 1.5 mg/kg suxamethonium were injected, followed by a total dose of 0.1 mg/kg vecuronium. Blood samples were taken through a central venous line at eight time points from before induction until 60 min after extubation for analysis of adrenaline, noradrenaline (by HPLC/ECD), antidiuretic hormone (ADH), adrenocorticotropic hormone (ACTH), and cortisol (by RIA). In addition, systolic arterial pressure (SAP) heart rate (HR), arterial oxygen saturation (SpO2), and recovery from anaesthesia were observed. RESULTS. Group mean values are reported; biometric data from both collectives were comparable (Table 1). Plasma levels of adrenaline (52 vs. 79 pg/ml), noradrenaline 146 vs. 217 pg/ml), and cortisol (82 vs. 165 ng/ml) were significantly lower in the propofol group (Table 2, Figs. 1 and 3). Plasma levels of ADH (4.8 vs. 6.1 pg/ml) and ACTH (20 vs. 28 pg/ml) did not differ between the groups (Table 2, Figs 2 and 3). SAP (128 vs. 131 mmHg) was comparable in both groups, HR (68/min vs. 83/min) was significantly lower in the propofol group, and SpO2 (97.1 vs 97.4%) showed no significant difference (Table 3). Recovery from anaesthesia was slightly faster in the propofol group (following of simple orders 1.9 vs. 2.4 min, orientation with respect to person 2.4 vs. 3.4 min, orientation with respect to time and space 2.8 vs. 3.7 min), but differences failed to reach statistical significance. CONCLUSIONS. When compared with isoflurane inhalation anaesthesia, moderation of the endocrine stress response was significantly improved during and after TIVA with propofol and fentanyl. Slightly shorter recovery times did not lead to an increased stress response. With respect to intra- and postoperative stress reduction, significant attenuation of sympatho-adrenergic reaction comparable SAP and reduced HR, sympatholytic and hypodynamic anaesthesia with propofol and fentanyl seems to be advantageous for patients with cardiovascular and metabolic disorders. For this aim, careful induction and application of individual doses is essential.