S. Ramanathan

Vasopressor therapy for hypotension due to epidural anesthesia for cesarean section

Maternal hemodynamic changes and neonatal acid‐base status were assessed in 127 healthy patients undergoing elective cesarean section under epidural anesthesia. An impedance cardiograph was used to measure stroke volume (SV), ejection fraction (EF) and end‐diastolic volume (EDV). In addition, neonatal umbilical venous and arterial Po2, Pco2, pH, base excess, lactate, pyruvate, excess lactate, and L/P ratio were measured at birth. Patients were divided into three groups. Group 1 (n = 53) required no vasopressor (normotensive controls). In Group 2 (n = 37), mean blood pressure (BP) decreased from 90 mmHg to 67 mmHg (12.0 to 8.9 kPa), and ephedrine was given in 5‐mg increments to maintain systolic BP>100 mmHg (13.3 kPa). In Group 3 (n = 37), BP decreased from 83 mmHg to 62 mmHg (11.1 to 8.2 kPa), and phenylephrine was administered in 100 μg increments to maintain systolic BP>100 mmHg (13.3 kPa). In Groups 2 and 3 the SV and EDV decreased 43% and 33% respectively when hypotension developed. Both vasopressors restored BP, SV and EDV to near baseline values. Neonatal Apgar scores and acid‐base profiles were not signficantly different among the three groups of neonates, nor were they different between the two hypotensive groups. It is concluded that: 1) transient maternal hypotension does not affect neonatal acid‐base status; 2) both ephedrine and phenylephrine increase cardiac preload; and 3) an α agent like phenylephrine does not cause fetal acidosis when used for treating maternal hypotension.

The humidification of anaesthetic gases: its importance and control.

RésuméLes auteurs ont décrit les différentes définitions concernant ľhumidité des gaz ďanesthésie et ont étudie les facteurs capables ďinfluencer sa régulation. Ils ont de plus démontré les effets néfastes de ľemploi des gaz secs qui déssèchent les muqueuses respiratoires et élèvent le pourcentage des complications pulmonaires qui suivent ľanesthésie. Une revue du débit de vapeur ďeau des systèmes en usage courant a été suivie par une description des mesures prises pour élever ľhumidité des gaz respirés par les malades durant ľanesthésie. Ils ont aussi recommandé la réduction de ľhumidité durant les périodes ďhyperthermie et les précautions à prendre pour éviter la contamination microbienne des équipements ďanesthésie, un risque augmenté durant ľhydratation des gaz aspirés par les malades.

Assessing local anesthetic effect using the mouse tail flick test

We used the tail flick test to quantify duration of local anesthetic-induced conduction block in the mouse. Using a baseline tail flick latency (TFL) between 1.0 and 2.5 sec, sensory block was considered present if TFL was > or = 4 sec. Two 20-microL local anesthetic injections were made on opposite sides of the tail base. TFL was tested every 10 min, and local block duration was interpreted as the time to return of TFL to < 4 sec. We tested three different concentrations of procaine (1%, 2%, and 4%), tetracaine (0.125%, 0.5%, and 1%), and lidocaine (0.5%, 1%, and 2%) with and without epinephrine. The testing method could discriminate between the duration of the various local anesthetic concentrations used. For the 1% concentrations, the duration of sensory block was 2 +/- 4 min (S.D.) for procaine, 20 +/- 10 min for lidocaine, 40 +/- 10 min for tetracaine, and 66 +/- 15 min for lidocaine with epinephrine. We found this to be a simple and reliable means of assessing local anesthetic conduction block in the mouse.

Prolongation of Spinal Anesthesia Differential Action of a Lipid Drug Carrier on Tetracaine, Lidocaine, and Procaine

This study evaluates prolongation of spinal anesthesia by incorporating local anesthetics in lipid formulation. The duration and intensity of local anesthetic effect produced by different concentrations of procaine (1%, 2%, 4%), lidocaine (1%, 2%, 4%), or tetracaine (0.5%, 1%, 2%) dissolved in normal saline were compared to those produced by the same concentration of drugs in lipid (iophendylate) solution. Fifty rabbits with chronic indwelling subarachnoid catheters were divided into ten equal groups. Three days after the operation the catheters were injected with aqueous solutions of the anesthetics, and 24 h later each animal received an equivalent dose of the corresponding drug in free-base form dissolved in iophendylate. The duration and intensity of motor blockade were assessed using a modified Bromage scale. A separate group of animals received plain normal saline and, 24 h later, iophendylate alone. The Kruskal-Wallis test followed by the Tukey-type test for nonparametric multiple comparisons and the Mann-Whitney and Friedman tests were used for statistical analysis at P less than 0.05. Normal saline or iophendylate alone did not produce any motor blockade. Our data show that iophendylate preparations of local anesthetics produce prolonged but less intense motor blockade than the aqueous solutions, except for tetracaine 0.5% in iophendylate, which produced shorter duration of motor blockade. The reduced intensity of motor blockade may be explained by decreased availability of local anesthetic at the nerve tissue due to storage of drug in the lipid depot. The increased duration of blockade signifies a sustained release of drug from the depot.

Decreases in Electric Thoracic Impedance During transurethral Resection of the Prostate: an Index of Early Water Intoxication

Thoracic impedance of 18 patients undergoing transurethral resection of the prostate was measured 15 minutes preoperatively, and 30 and 60 minutes after the start of the operation. Impedance variations were compared to variation in 1) cardiac output, 2) serum sodium osmolality and 3) alveolar-arterial oxygen tension difference. Thoracic impedance, initially 24.6 plus or minus 0.3, decreased to 23.8 plus or minus 0.5, 30 minutes after the onset of the operation (p less than 0.0005) and 22.9 plus or minus 0.5, 30 minutes later (p less than 0.01 from previous reading and 0.0005 from control). Patients in whom impedance had decreased 10 per cent or more from control values received 10 mg. furosemide intravenously 60 minutes after the onset of the operation. This therapy permitted the restoration of impedance values, cardiac output, alveolar-arterial oxygen tension difference and serum sodium osmolality to values statistically similar to those found in the 10 patients who had not sustained such precipitous decreases in impedance within 60 minutes. We believe that the measurement of thoracic impedance during transurethral prostatic surgery offers the most sensitive index of early water intoxication. Measurements can be obtained without delay in the operating room and, thus, permit immediate correction of the condition.

A two‐dose epidural morphine regimen in cesarean section patients: pharmacokinetic profile

The maternal pharmacokinetics, metabolism of, and possible neonatal transmission of epidural morphine in cesarean section patients were investigated. Maternal plasma, breast milk, and maternal and neonatal urine concentrations of unconjugated and conjugated (UM and CM) morphine were measured in patients given two 5‐mg doses of epidural morphine for post‐cesarean section analgesia. The first dose was administered after delivery and the second dose 24 h later. Maternal venous blood samples (n = 10) were collected at times 0, 0.25, 0.5, 1, 2, 3, 4, 6, 12, and 24 h after each dose, and maternal urine was collected for three consecutive 24‐h periods (n = 30). Maternal breast milk (n = 30), and neonatal urine samples (n = 20) were also collected. Serum, urine, and breast milk UM and CM levels were measured using radioimmunoassay. Pharmacokinetic values were calculated using noncompartmental analysis. The results were expressed as mean ± 1 s.e. mean and analyzed using repeated measures analysis of variance and the paired t‐test. Maternal serum UM remained 40–50% higher, and CM 50–100% higher in the first hour following dose 2 than the respective values after dose 1 (P < 0.05). Values for AUC, AUMC, Tl/2, and MRT increased 28%, 83%, 35% and 36%, respectively, with the second dose (P < 0.05), while CI decreased 19% (P < 0.05) with no significant difference in Vss. Total urinary excretion of morphine decreased significantly from 1.98 ± 0.15 mg on day 1 to 1.6 ± 0.2 mg and 0.19 ± 0.002 mg on days 2 and 3, respectively (P < 0.01). Breast milk and neonatal urine contained negligible amounts of morphine, signifying minimal neonatal transfer.

A two-dose epidural morphine regimen for cesarean section patients: therapeutic efficacy

A single dose of epidural morphine (EM) usually produces 24 h of post‐cesarean section (CS) analgesia and patients require supplemental analgesics beyond this period. This study assesses if a second dose of EM administered 24 h after the first one offers superior therapeutic efficacy compared to conventional analgesics. Patients (n = 100) were randomized to receive one or two doses of epidural morphine. In all patients, EM 5 mg was administered after delivery. After 24 h patients received epidurally either normal saline (n = 50, Group 1) or morphine 5 mg (n = 50, Group 2). An independent observer used a visual analogue scale to assess nausea, itching, and analgesia 24 h after each injection. Results were expressed as mean ± 1 s.e. mean and analyzed using nonparametric methods. The second dose of EM produced a significantly lower incidence and severity of nausea and itching than did the first dose (P<0.01) in Group 2 with no difference in analgesia. The second day postoperative pain score in Group 1 was significantly greater than the first day score in the same group, and significantly greater than the severity score in Group 2. Only 36% of patients receiving two doses of EM required supplemental analgesics beyond 48 h compared to 76% of those receiving one dose (P<0.01). No serious complications were noted. In summary, the use of a second dose of EM for post‐CS analgesia produces better analgesia and reduces the need for oral analgesics. The second dose produced fewer side‐effects, probably due to acute tolerance to morphine.

Plasma β-Endorphin Levels in the Umbilical Cord Blood of Preterm Human Neonates

Maternal venous (MV) and neonatal umbilical venous (UV) and umbilical arterial (UA) plasma β-endorphin concentrations were measured at birth in two groups of patients undergoing cesarean section (CS).

Murine auto- and cross-tolerance to volatile anaesthetics.

Auto-tolerance and cross-tolerance to halothane, isoflurane and enflurane were tested on 36 mice divided into three equal groups. Each group was first exposed to increasing concentrations of either of the three anaesthetics on 13 occasions. The concentration at which each mouse lost its righting reflex during successive exposures in a rotating cage was noted. Cross-tolerance was assessed by comparing the number of mice which had lost their righting reflexes during their first exposure to a given anaesthetic agent to the number which lost it after having been exposed to another anaesthetic.All animals developed auto-tolerance to halothane, isoflurane and enflurane. Cross-tolerance was noted only between mice exposed to isoflurane and enflurane and between mice exposed to halothane and subsequently anaesthetized with isoflurane, but not vice versa.RésuméL’auto-tolérance et I’ inter-tolérance à I’halothane, l’ isoflurane et I’ enflurane furent étudiées chez 36 souris, divisiés en trois groupes égaux. Chaque groupe fut d’abord exposé à des concentrations croissantes de chacun des trois anesthésiques à treize reprises. La concentration à laquelle chaque souris perdit son réflexe de redressement fut notée. Le développement de I’intertolerance fut obtenu en comparant le nombre de souris ayant ayant perdu leur reflexe de redressement durant la premiire exposition à un anesthésique particulier au nombre I’ayant perdu après exposition à un autre anesthésique. Tous les animaux développèrent une autototoérance à l’halothane, I’isofiurane et l’enflurane. L’inter-tolérance fut découverte seulement chez les souris exposéees à l’ isofiurane et l’enflurane et chez celles exposées d’abord à l’halothane et ensuite à l’isofiurane, mais non pas vice versa.

Considerations on impedance cardiography.

Impedance cardiography is an electronic plethysmographic technique which provides information on cardiac stroke index, myocardial performance, thoracic fluid content and peripheral circulation. The method has gained popularity in recent years because it is not invasive. While less precise in absolute terms than invasive methods the results are reproducible, and the technique accurately assesses variations in measurements. It may be used in most anaesthetized patients without the possibility of any of the complications which sometime accompany the use of more precise invasive methods.RéSUMéLa recherche de méthodes non-invasives pour la mesure du débit cardiaque, du travail myocarde, du contenu fluide du thorax et de l’état de la circulation périphérique, a gagne du terrain durant la dernière decennie. La cardiographie par impedance est un exemple des travaux qui ont porte fruit a ce sujet ; découverte dès 1930, elle ne fut perfectionnée et utilisée a fond que trente ans plus tard, au cours des explorations lunaires Appolon. II s’agit d’une méthode pléthysmographique électronique qui mesure l’impédance thoracique durant les phases du cycle cardiaque. Une formule dérivée par Kubicek et coll. permet le calcul du volume d’éjection, et done du debit cardiaque, en fonction de changements d’impédance thoracique. La méthode permet aussi de mesurer le rapport des durées respectives de la contraction isovolémique ventriculaire et de la phase d’éjection (index Heather). Hill et coll. ont établi une formule par laquelle il est possible de mesurer la durée d’éjection ventriculaire gauche et Siegel et coll. pour leur part ont conçu une methode de calcul de la contraction isométrique du myocarde en fonction de changements d’impédance thoracique. Le cardiogramme par impédance s’obtient par l’encerclement de la base du cou et de la poitrine du malade par quatre rubans (2.5 cm de large) en mylar aluminisé. Un courant électrique de 4 milliampéres et de 100 kilohertz est introduit entre la seconde et la troisième électrode; son voltage amplifié permet d’obtenir la courbe des variations d’impédance thoracique par rapport au temps.La pléthysmographie des membres s’obtient par le placement des électrodes autour de Textrémité choisie dont elle mesure la circulation sanguine. Plusieurs auteurs ont souligné le manque de précision de cette technique: on reconnaît de facon générate, qu’elle surestime les valeurs mesurees. Cependant, la reproductibilite des resultats rend la technique utilisable pour mesurer des changements plutôt que des valeurs absolues.Les erreurs au début sont attribuables au fait qu’on a assume que le thorax était cylindrique et a contenu homogène; la morphologie individuelle des patients introduit des variations particulières qui se retrouvent dans la mesure de leur impédance thoracique. La cardiographie par impédance possède deux avantages importants: la simplicité relative des appareils de mesure et leur prix economique. De plus, elle peut s’employer durant l’anesthésie sans aucune crainte des complications qui accompagnent parfois l’emploi de méthodes invasives plus précises. La recherche du méthodes de mesures non-invasives demeure une priorité et nous croyons que la cardiographie par impédance represente une avance importante dans ce sens.