Paul L. Goldiner

Factors influencing postoperative morbidity and mortality in patients treated with bleomycin.

Patients treated with bleomycin are at risk of developing the acute adult respiratory distress syndrome post-operatively. In a prospective study of 12 patients who had received bleomycin preoperatively and were undergoing removal of retroperitoneal lymph nodes or pulmonary metastases several preventive factors were established. These were the use of low concentrations of inspired oxygen during operation and in the immediate postoperative period, careful monitoring of fluid replacement, and restriction of crystalloids in favour of colloids.

Heterogeneity of presynaptic muscarinic receptors involved in modulation of transmitter release

In order to extend the characterization of muscarinic receptors at presynaptic sites their inhibitory effect on the stimulation-evoked release of [3H]noradrenaline and [3H]acetylcholine from different axon terminals was studied and the dissociation constants and potencies of different antagonists were estimated, in guinea-pig and rat. While oxotremorine reduced the release of [3H]acetylcholine and [3H]-noradrenaline in a concentration-dependent manner from different release sites (Auerbach plexus, noradrenergic neurons in the right atrium, cerebral cortex), McN-A 343, an M1 receptor agonist, enhanced their release evoked by field stimulation. When the inhibitory effect of oxotremorine on transmitter release was studied, pancuronium, pirenzepine and atropine were competitive antagonists of presynaptic muscarinic receptors located on the noradrenergic axon terminals of the atrium. While atropine and pirenzepine inhibited the muscarinic receptors of cholinergic axon terminals in the Auerbach plexus, pancuronium and gallamine had a very low affinity. Significant differences were found in the affinity constants of antagonists for muscarinic receptors located in the cholinergic axon terminals of Auerbach plexus and cerebral cortex, and noradrenergic axon terminals of the atrium. While atropine and pirenzepine exerted similar effects on these presynaptic sites, pancuronium, gallamine and (11-(2-[diethylamino)-methyl)-1-piperidinyl)acetyl)-5, 11-dihydro-6(1-pyrido(2,3-b)(1,4)-benzodiazepin-6-on) were much more effective on muscarinic receptors controlling acetylcholine release from the cerebral cortex and noradrenaline release from the heart. There was more than 100-fold (2.0 pA2 units) difference in affinities of these antagonists.(ABSTRACT TRUNCATED AT 250 WORDS)

Massive Blood Replacement: Correlation of Ionized Calcium, Citrate, and Hydrogen Ion Concentration

Fifty-three patients were studied intraoperatively during massive transfusion of CPD-preserved blood and fresh frozen plasma (FFP). Baseline concentrations of total calcium (Ca), ionized calcium (Ca2+), albumin, total protein, and hydrogen ion concentration [H+] were measured prior to transfusion, at intervals during transfusion of 2500 ml of blood, and at the end of transfusion. Systemic arterial pressure (BPI, central venous pressure (CVP) and/or pulmonary artery wedge pressure (PAW), and corrected Q-T intervals on electrocardiographic tracings were measured at the time blood samples were obtained. Ca2+ decreased from 2.07 ± 0.03 mEq/L at baseline to 1.52 ± 0.05 mEq/L (p < 0.01) during transfusion at peak rates of 33 ± 3.2 ml/kg/hr. Following completion of transfusion, Ca2+ was significantly higher than at peak rates of transfusion, but still below baseline. Serum citrate levels rose from a baseline value of 1.87 ± 0.17 mg/dl to 6.30 ± 0.49 mg/dl (p < 0.01) at peak rate of transfusion and fell to 4.76 ± 0.48 immediately upon completion of transfusion (p < 0.011. The changes in Ca2+ and serum citrate levels showed a strong statistical correlation with each other. [H+] increased, but not significantly, at peak rates of infusion; after completion of transfusion, [H+] was significantly lower than during peak rates of transfusion. Ca levels were 4.10 ± 0.05 mEq/L at baseline, 3.90 ± 0.05 mEq/L at peak rates of infusion, and 3.89 ± 0.06 mEq/L after transfusion was completed. Albumin levels at the same sampling intervals were 3.60 ± 0.07, 3.71 ± 0.06, 3.87 ± 0.07 g/dl, respectively. Total protein levels were 5.95 ± 0.07, 5.67 ± 0.07, and 5.88 ± 0.09 g/dl, respectively. Corrected Q-T intervals were significantly prolonged at peak rates of transfusion and upon completion of transfusion. Correlation between changes in Ca2+ and corrected Q-T intervals was statistically significant. However, hemodynamic variables remained stable throughout the period of observation.Massive transfusions depressed Ca2+ due to administration of citrate, but this was only transient. Ca2+ rapidly returned to normal levels as citrate was redistributed and metabolized. The changes in Ca2+ were without hemodynamic significance. Clinically significant metabolic acidosis due to transfusion was not observed. We conclude, therefore, that as long as circulating volume is maintaines, as determined by measurement of CVP or PAW, calcium salts need to be administered during blood replacement, either empirically on the basis of rate or volume or transfusion, or on the basis of changes in samples indicate the development of metabolic acidosis.

Hypoxemia during hemodialysis.

Five mechanically ventilated patients were studied during hemodialysis. The aim was to determine if hypoxemia would develop, and to identify the causes. Respiratory variables (dynamic compliance, peak airway pressure, CO2production); oxygen uptake, and transport variables (alveolar and arterial PO2, pulmonary venous admixture, oxygen consumption); respiratory quotient; pulmonary vascular resistances and white blood cells (WBC) were measured. PaO2 decreased during dialysis, as did PaO2. However, the fall in alveolar oxygen tension failed to explain the hypoxemia. Lung volume did not change significantly, because dynamic compliance, peak airway pressure, and pulmonary vascular resistance were not modified. CO2 losses through the dialysis coil were of little clinical significance. WBC count fell significantly. The authors conclude that ventilation/perfusion and diffusion abnormalities related to leuko-agglutination are responsible for hypoxemia during dialysis.

Modulation of stimulation-evoked release of newly formed acetylcholine from mouse hemidiaphragm preparation

SummaryA radioisotope method has been developed for measuring the stimulation-evoked release of acetylcholine without the use of cholinesterase inhibitors from the mouse hemidiaphragm preparation which had been loaded with 3H-choline. Evidence has been obtained that 3H-choline was taken up by and released from both innervated and non-innervated mouse hemidiaphragm preparations. However, it was released in the form of 3H-acetylcholine in response to electrical field stimulation only from the innervated preparations. Long lasting (51 min) S1 stimulation of the preparations exhausted the radioactive acetylcholine stores to the extent that S2 did not evoke any release of 3H. These data suggest that when the labelled acetylcholine stores become exhausted, the labelled choline, still present in the tissue, cannot be released by electrical stimulation. Tetrodotoxin (1 μmol/1) administration and Ca withdrawal inhibited, 20–100 μmol/l 4-aminopyridine enhanced the release of 3H-acetylcholine in response to electrical stimulation. Activation of the presynaptic muscarinic receptors by the agonist oxotremorine (50 μmol/l) decreased the liberation of 3H-acetylcholine. The muscarinic antagonist atropine (1 μmol/l) abolished the inhibitory effect of oxotremorine and by itself increased the evoked release of the newly formed 3H-acetylcholine. Adenosine (50 μgmol/l) reduced the evoked release of radioactivity. Theophylline (30 μmol/l) prevented the inhibitory effect of adenosine and itself enhanced the release. Xylazine (1 μmol/l), an alpha2-adrenoceptor agonist did not affect the release. It is concluded that the stimulation-evoked release of 3H-acetylcholine from the mouse phrenic nerve hemidiaphragm preparation preloaded with 3H-choline is derived from the motor nerves. The release of acetylcholine is modulated by activation of presynaptic muscarinic and adenosine receptors.

New Applications of Two-Dimensional Transesophageal Echocardiography in Cardiac Surgery

This article describes new applications of two-dimensional transesophageal echocardiography (2D-TEE), including (1) detection of pleural fluid (PF) and atelectasis (AT), and (2) evaluation of various cannulation techniques. The left and right pleural spaces were visualized by rotating the probe counterclockwise and clockwise, respectively, from the four-chamber view. PF was depicted as a crescent-shaped echo-free space, enclosed by the lung and posterior chest wall on both sides. AT was often accompanied by PF and was depicted as a less echogenic area in the lung parenchyma. During removal of PF, the echo-free space gradually decreased in size to the point of disappearing completely, while the lung parenchyma expanded and became more echogenic. TEE was advantageous in detecting PF and AT located in the most dorsal parts of the pleural space and lung parenchyma. The aorta acted as an acoustic window on the left side. TEE was found useful in evaluating the cannulae position of the intraaortic balloon pump (IABP) and ventricular assist device (VAD), and femoral cannulae for cardiopulmonary bypass (CPB). During use of the IABP, the chamber and shaft were visualized clearly and both malposition of the catheter tip and malfunction of the balloon were easily detected. For VAD, TEE readily showed the collapse of the ventricular cavity due to excessive drainage of blood from the left ventricle, as well as the favorable result of immediate reduction of flow rate. For femorofemoral extracorporeal bypass, TEE detected improper position of the venous cannula. These new applications of TEE can be performed with minimal manipulation of the probe, enabling early detection of the problems and initiating timely and appropriate therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Neuromuscular and cardiovascular effects of pipecuronium

Pipecuronium bromide (Arduan) is a bisquaternary, steroid-type neuromuscular blocking agent in clinical use in Eastern Europe. Before its introduction into clinical practice in the USA, in the first phase of this study the neuromuscular potency of pipecuronium was determined under “balanced” and enflurane anaesthesia by the cumulative log dose-response method in 30 patients each. In the second phase the intubation and onset times, clinical duration of the first and repeated doses, spontaneous recovery index, reversibility of its residual neuromuscular effect by an anticholinesterase and its effect on heart rate and blood pressure was compared with the same variables observed in patients, anaesthetized with identical techniques but who had received vecuronium or pancuronium. The neuromuscular potency of pipécuronium was greater under enflurane [ED95 = 23.6 ± 1.1 μg · kg−1 (mean ± SEM)] than under balanced (ED95 = 35.1 ± 17 μg · kg−1) anaesthesia. Pipecuronium was more potent than vecuronium under both balanced (ED95 = 45.8 μg · kg−1) and enflurane anaesthesia (ED95 = 27 A μg · kg−1). Following the administration of 2 × ED95 doses there were no clinically significant differences in the intubation or onset times of pipecuronium, vecuronium and pancuronium. Under balanced anaesthesia the clinical duration of 2 × ED95 dose of pipécuronium (110.5 ± 0.3 min) or pancuronium (115.8 ± 8.1 min) were similar and about three times longer than that of vecuronium (36.3 ± 2.1 min). The recovery indices of pipécuronium (44.5 ± 8.2 min) and pancuronium (41.3 ± 4.2 min) were also similar and about three times longer than that of vecuronium (14.3 ± 1.4 min). Residual neuromuscular block of the three muscle relaxants could be equally well reversed by anticholinesterases at the end of anaesthesia. The 2 × ED95 doses of pipécuronium or vecuronium had no significant effect on heart rate or blood pressure. Pancuronium increased heart rate by about 20 per cent. Pipecuronium is preferable to pancuronium for the production of muscular relaxation for relatively long operations, when it is desirable to avoid acceleration of heart rate.RésuméLe bromure de pipécuronium (Arduan) est un curare biquaternaire de type stéroïdien employé en Europe de l’Est. Nous avons mesuré quelques unes de ses propriétés avant d’en recommander l’usage clinique aux Etats-Unis. Dans un premier temps, nous avons déterminé sa puissance en comparant la réponse neuromusculaire au logarythme de la dose cumulative chez deux groupes de 30 patients. Nous avons établi que sa DE95 était de 23,6 ± 1,1 μg · kg−1 (moyenne ± erreur-type) sous anesthésie á l’enflurane, et de 35,l ± 17 μg kg−1 sous neurolepanesthésie tandis que ces deux valeurs étaient respectivement de: 27,4 μ-kg−1 et 45,8 μg · kg−1 pour le vécuronium. Dans un deuxième temps, nous avons établi quen présence de conditions anesthésiques identiques, l’injection d’une dose égale 2 × DE95 s’accompagnait de temps de latence avant le debut d’action et l’instauration de conditions propices à l’intubation virtuellement semblables pour le pipécuronium, le pancuronium et le vécuronium tandis que sa durée d’action s’etablissait dans l’ordre à 110,5 ± 0,3 min, 115,8± 8,1 min et 36,3 ± 2,1 min et son index de récupération à 44,5 ± 8,2 min, 41,3 ± 4,2 min et 14,3 ± 1,4 min pour ces mémes produits. A la fin de l’intervention, le bloc neuromusculaire residuel était aussi facile à contrer avec un inhibiteur de la cholinestérase quelque soit le myorelaxant employé. Le pipécuronium et le vécuronium à raison d’une dose égale à 2 × DE95 ne modifièrent ni la pression artérielle ni la fréquence cardiaque tandis que cette dernìere augmentait de 20 pour cent avec le pancuronium. Il semble done que si on veut utiliser un myorelaxant de longue durée sans accélérer le pouls, on doive préférer le pipécuronium au pancuronium.

Intraoperative assessment of pulmonary vein flow.

This study was undertaken to assess the suitability for intraoperative pulmonary vein flow measurements in 15 patients undergoing coronary artery bypass grafting. Using two‐dimensional color Doppler transesophageal echocardiography, all four pulmonary veins—right upper and lower and left upper and lower pulmonary veins were easily visualized. Pulmonary vein flow was pulsatile. J wave occurred in the ventricular systole with relaxation of the left atrium and K wave in the ventricular diastole with relaxation of the left ventricle. There were differences in suitability for flow measurements among four pulmonary veins: (1) consistent visualization; (2) stable visualization throughout measurement; (3) minimal angle between ultrasonic beam and pulmonary vein course; and (4) minimal shift of sampling volume during measurement. The left pulmonary veins were suitable for flow velocity measurement by transesophageal echocardiography. The left lower pulmonary vein was stable for visualization once it was visualized although the angle was occasionally large. The left upper pulmonary vein was consistently visualized although the angle was occasionally large. On the other hand, the right pulmonary veins were unsuitable for flow measurement. Since sampling volume shifted in the direction of the long axis by the average of 5 to 6 mm during cardiac cycle, it should be positioned inside of the pulmonary vein at about 5 mm from the orifice of the left atrium.

Effect of Transcutaneous Nerve Stimulation on Postoperative Pain after Thoracotomy

A prospective randomized double-blind study was undertaken to evaluate the efficacy of transcutaneous nerve stimulation (TNS) in relief of acute post-thoracotomy pain by comparing postoperative narcotic requirements in 22 patients having TNS and in 22 patients having sham electrical stimulation. All patients in both groups had intrathoracic malignancies. When TNS was used, 22.7% of the patients required no narcotics in the first 24 hr postoperatively. All patients having sham stimulation required postoperative narcotics.

Direct evidence that pancuronium and gallamine enhance the release of norepinephrine from the atrial sympathetic nerve by inhibiting prejunctional muscarinic receptors

The effect of different non-depolarizing muscle relaxants (gallamine, pancuronium, vecuronium, D-tubocurarine) on [3H]norepinephrine release in response to electrical stimulation was studied in isolated guinea-pig atrium. High pressure liquid chromatography combined with electrochemical and radiochemical detection revealed that the released radioactivity was mainly in the form of [3H]norepinephrine release. Oxotremorine, a pure muscarinic agonist, reduced the release of tritium. Gallamine and pancuronium, like atropine, prevented the inhibitory effect of oxotremorine. D-Tubocurarine and vecuronium had no such effect. These findings indicate that gallamine and pancuronium exert a presynaptic antimuscarinic, atropine-like effect, by inhibiting muscarinic receptors located on the axon terminals of sympathetic neurons thereby enhancing norepinephrine release. It is suggested that this phenomenon might play some role in tachycardia observed during surgical anaesthesia when gallamine or pancuronium have been administered.