Invasive monitoring in obstetrics.
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Catheterization, Peripheral↗
Biomedical subjects
S Ramanathan
Publications and source records attributed to S Ramanathan.
Determination of a new antifilarial drug, UMF-058, and mebendazole in whole blood by high-performance liquid chromatography.
A rapid and selective high-performance liquid chromatographic assay for simultaneous quantitative determination of a new antifilarial drug (UMF-058, I) and mebendazole (MBZ) is described. After a simple extraction from whole blood, both compounds were analysed using a C18 Nova Pak reversed-phase column and a mobile phase of methanol-0.05 M ammonium dihydrogenphosphate (50:50, v/v) adjusted to pH 4.0, with ultraviolet detection at 291 nm. The average recoveries of I and MBZ over a concentration range of 25-250 ng/ml were 92.0 +/- 7.7 and 84.4 +/- 4.4%, respectively. The minimum detectable concentrations in whole blood for I and MBZ were 7 and 6 ng/ml, respectively. This method was found to be suitable for pharmacokinetic studies.
Animals↗
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.
Anesthesia, Local↗
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, T1/2, 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).(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Electrocardiographic changes during cesarean section: a cause for concern?
A Holter monitor was used to record ST segment changes during cesarean section in 170 consecutive healthy parturients starting 2 h before and ending 3 h after surgery. Lumbar epidural anesthesia (LEA, n = 120) or subarachnoid anesthesia (SA, n = 50) was used. Transthoracic 2-D echocardiograms were obtained in 30 patients from the LEA group. ST depression or elevation occurred 160 times in 44 patients from both groups. Ninety-eight percent of these changes occurred between induction of anesthesia and the end of surgery, with 78% of the episodes registering -1 mV. In the LEA group, the number of episodes tended to increase after delivery, but in the SA group, the frequency remained constant. ST segment depression was recorded in 38% and 14% of patients in the LEA and SA groups, respectively (P < 0.05, x2 analysis). No wall motion abnormality was noted in the echocardiogram during ST segment depression. Neither the 12-lead electrocardiogram nor plasma myocardial specific creatine kinase suggested myocardial damage. The operative events, alone or in combination, including hypertension, tachycardia, hypotension, bradycardia, air embolism (precordial Doppler) were neither specific nor sensitive as predictors of ST segment change (stepwise logistic regression). Tachycardia was associated with ST segment changes in 10% of time epochs (5 min) (P = 0.05, x2 analysis). Thus, ST segment changes during cesarean section are not caused by myocardial ischemia and are not of any clinical consequence.
Adult↗
Glucose in epidural catheter aspirate.
Frequently fluid may be aspirated from epidural catheters during epidural anesthesia/analgesia. This fluid may be either cerebrospinal fluid or local anesthetic. Several methods for differentiation of the two fluids have been recommended. In this study, the reliability of the "glucose test" was analyzed. Epidural catheters were inserted into 43 healthy, nondiabetic parturients and then gently aspirated. Aspirate was tested for glucose using glucose oxidase paper. Positive aspirates were assessed for the presence of prealbumin, which is a protein marker for cerebrospinal fluid. Of the patients undergoing cesarean section, 17 of 27 patients yielded a glucose-positive aspirate, and of the patients undergoing labor analgesia, 6 of 16 patients were found to be positive for glucose. None of these patients developed total spinal anesthesia or postdural puncture headache. Visually, none of the aspirates were significantly blood-tinged, blood being a possible source of glucose. When the glucose-positive aspirates were subjected to immunoelectrophoresis, 6 of 7 aspirates revealed a prealbumin band. In conclusion, the glucose test for cerebrospinal fluid may be misleading. The source of this glucose may be normal cerebrospinal fluid drainage into the epidural space.
Analgesia, Epidural↗
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.
Anesthesia, Spinal↗
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.
Adult↗
Uptake and distribution of bupivacaine and morphine after intrathecal administration in parturients: effects of epinephrine.
This study examines the plasma pharmacokinetics of bupivacaine and morphine and the urinary excretion of morphine administered for spinal anesthesia for cesarean section. Patients received 12 mg of hyperbaric bupivacaine and 0.6 mg of morphine with either 0.2 mL of normal saline (plain, n = 15) or 0.2 mg of epinephrine (n = 15). Venous blood and urine were collected at 0, 0.25, 0.5, 1, 2, 3, 6, 12, and 24 h. Total and unconjugated morphine (UCM) in plasma and urine were measured using radioimmunoassay, and plasma bupivacaine was measured by gas chromatography. Results were expressed as mean +/- SE and analyzed using Student's t-test at P less than 0.05. In the epinephrine group, plasma bupivacaine peaked at 15 min and remained approximately 30% higher (P less than 0.05) at 0.25, 0.5, and 1 h than in the plain group, which peaked at 30 min. Although UCM peaked at 3 h in both groups, the plasma levels remained approximately 66% lower in the epinephrine group. In the epinephrine group, bupivacaine had a smaller volume of distribution at steady state, and morphine had a more rapid clearance, shorter t1/2 beta, and smaller area under the curve compared with the plain group (P less than 0.05). Only 45% +/- 5% and 31% +/- 3% of morphine was recovered in the urine in the plain and epinephrine group, respectively (P less than 0.05). In conclusion, epinephrine added to a bupivacaine-morphine mixture increases the initial systemic uptake of bupivacaine and decreases the absorption and urinary excretion of morphine from the intrathecal space.
Adult↗
A rat sciatic nerve model for independent assessment of sensory and motor block induced by local anesthetics.
The purpose of this study was to develop a reliable model to independently quantify motor and sensory block produced by local anesthetics. The sciatic nerve was blocked in 52 rats by injecting 0.2 mL of 0.125%, 0.25%, 0.5%, or 0.75% bupivacaine (n = 13 for each concentration). Accurate needle placement was achieved using a nerve stimulator at 0.2 mA and 1 Hz. Ten control rats received 0.9% saline (n = 5) or sham nerve stimulation (n = 5). Motor block was assessed by measuring hindpaw grip strength with a dynamometer. Sensory block was determined by measuring hindpaw withdrawal latency from radiant heat. The intensity of both motor and sensory block measured at 30-min intervals was plotted against time until full recovery to obtain the area under the curve. Intergroup comparisons using analysis of variance showed increasing area under the curve with increasing concentrations of bupivacaine for motor blocks (P < 0.05 for all intergroup comparisons except 0.5% vs 0.75%) and sensory blocks (P < 0.05 for all intergroup comparisons). Normal saline or sham nerve stimulation did not result in any motor or sensory block.
Animals↗
Prolongation of epidural anesthesia using a lipid drug carrier with procaine, lidocaine, and tetracaine.
This study evaluated the effect of a lipid drug carrier (iophendylate) on epidural anesthesia. The intensity and duration of motor blockade produced by aqueous and lipid preparations of local anesthetics were assessed in rabbits with long-term indwelling catheters in the epidural space. Motor blockades produced by procaine (1%, 2%, and 4%), lidocaine (1%, 2%, and 4%), and tetracaine (0.5%, 1%, and 2%) in normal saline solution were compared with the effects produced by equimolar amounts of the drug solutions in iophendylate. Procaine (4%) in aqueous solution produced motor blockade lasting 30 +/- 3.54 min (mean +/- SD) versus 84 +/- 4.18 min in lipid solution. Lidocaine (2% and 4%) in aqueous solution produced motor blockade lasting 41 +/- 4.18 and 65 +/- 6.12 min versus 39 +/- 4.18 and 118 +/- 10.1 min, respectively, in lipid solution. Aqueous tetracaine (0.5%, 1%, and 2%) produced motor blockade of 106 +/- 9.62, 189 +/- 6.52, and 273 +/- 26.8 min versus 284 +/- 14.7, 335 +/- 15.8, and 365 +/- 26.9 min, respectively, in their lipid counterparts. A control group of animals that received normal saline solution or iophendylate alone did not exhibit motor blockade. These results may be attributed to sustained release of local anesthetics from the lipid vehicle. Hence, lipid drug carriers may be effective in prolonging epidural anesthesia.
Anesthesia, Epidural↗
Perioperative maternal and neonatal acid-base status and glucose metabolism in patients with insulin-dependent diabetes mellitus.
Maternal and neonatal acid-base status and glucose metabolism were studied in 20 patients with insulin-dependent diabetes mellitus (group 1) undergoing elective cesarean section under lumbar epidural anesthesia. All patients were given glucose/insulin infusion before delivery. Fifteen healthy patients with iatrogenic hyperglycemia (group 2) and 15 healthy euglycemic patients (group 3) served as controls. Results were expressed as mean +/- 1 SE and were analyzed using analysis of variance and chi 2 analysis at P less than 0.05. No significant differences were seen at delivery either in maternal arterial and neonatal umbilical venous and arterial blood acid-base status or in neonatal Apgar scores among the three groups. Patients in groups 1 and 2 had larger blood glucose concentrations than those in group 3 (P = 0.01). Diabetic mothers and their neonates had a 25%-50% reduction in pyruvate concentration in maternal venous, and neonatal umbilical venous and arterial blood compared with that in the other two groups (P = 0.001). Postpartum neonatal hypoglycemia (less than 30 mg/dL) developed in seven of the group 1 neonates (P = 0.05). Thus, epidural anesthesia in diabetic women is associated with normal acid-base status in the mother and in the neonate. The data also show an increased incidence of neonatal hypoglycemia and altered maternal and neonatal glycolysis in patients with diabetes mellitus.
Adult↗
The maternal hemodynamic effects of bupivacaine-epinephrine mixture used for obstetrical anesthesia.
The maternal hemodynamic effects of bupivacaine (0.5%)-epinephrine (5 micrograms/ml) mixture used for lumbar epidural anesthesia were studied with an impedance cardiograph and an automated blood pressure device in term gravidas undergoing elective cesarean section. Following i.v. hydration with 2000 ml Ringer's lactate solution, 16 patients received bupivacaine-epinephrine mixture and 16 patients plain bupivacaine in 5-ml increments to a T4 level. Measurements were made before anesthesia, at T10 and at T4 sensory levels. Results were analyzed using analysis of variance (ANOVA) and the least significant difference method at P less than 0.05. In the epinephrine group, at T10 level, the diastolic (D) and mean (M) pressures decreased significantly 11 +/- 3, and 10 +/- 1% (mean +/- s.e. mean) respectively with no significant change in the S pressure. No significant changes were seen in the plain group. At T4, the S, D and M pressures decreased significantly 8 +/- 2, 18 +/- 4 and 16 +/- 2% in the epinephrine group. In the plain group the decrease in each one of these pressures was less than 5% and was not significant. In the epinephrine group, S, D and M pressures decreased significantly more than they did in the plain group at T10 and T4. Systemic vascular resistance decreased significantly from control values by 19 +/- 6% at T4 in the epinephrine group with no significant changes in the plain group.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Orthostatic hypotension, catecholamines, and alpha-adrenergic receptors in mitral valve prolapse.
The reported association of mitral valve prolapse with autonomic dysfunction and neuroendocrine abnormalities is derived from studies of patients selected because of symptoms or specifically referred for investigation. To determine whether such associations occur in nonreferred and unselected women with mitral valve prolapse, we measured blood pressure, heart rate, and norepinephrine response to standing in 13 volunteers with mitral valve prolapse and in 11 control subjects. Platelet alpha-adrenergic receptor quantity and affinity on standing also were determined in all persons. No significant differences were found between the groups in any of these measurements. Although small subsets of women with mitral valve prolapse may indeed have associated neuroendocrine epiphenomena and autonomic dysfunction, it is probably incorrect to generalize these findings to the vast spectrum of those with mitral valve prolapse.
Adolescent↗
Source of urinary cyclic AMP in response to calcitonin and parathyroid hormone in the rat.
Administration of calcitonin (CT) or parathyroid hormone (PTH) in rats, induced phosphaturia with a concomitant increase in urinary excretion of cyclic AMP. CT produced a rise in arterial cAMP and filtered cAMP, with no increase in urinary nephrogenous cAMP. PTH on the other hand, produced an elevation in urinary nephrogenous cAMP with no increase in arterial cAMP and filtered cAMP. These results indicate that the source of urinary cAMP after CT is non-renal, whereas after PTH it is renal in origin.
Animals↗
Supersensitivity of beta-adrenoceptor coupled adenylate cyclase in pulmonary tissue of the spontaneously hypertensive rat.
Basal adenylate cyclase activity was similar in plasma membranes prepared from the lungs of 12 week old spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto rats (WKY). However, sensitivity to Gpp[NH]p, isoproterenol plus GTP or Gpp[NH]p was significantly greater in the SHR. Beta-receptor density measured by [3H]DHA binding was unaltered. The dissociation constant, Kd, revealed a significantly greater binding affinity of the radioligand in the SHR (6.23 +/- 0.45 nM) compared with the WKY (8.53 +/- 0.82 nM). Activity of Gs was assessed by complementing S49 cyc- acceptor membranes with lung cholate extract. Basal activity of the reconstituted system was decreased 43% in the SHR. However, sensitivity to NaF, Gpp[NH]p, and isoproterenol plus Gpp[NH]p was significantly elevated. These data suggest that desensitization of the adenylate cyclase complex is not a generalized response to chronic hypertension. A tissue specific increase in sympathetic drive appears to be responsible for the lowered concentration of cardiac beta-adrenoceptors in the SHR. In contrast, both indirect and direct evidence indicate an enhanced functional sensitivity of pulmonary Gs in the hypertensive rats.
Adenylyl Cyclase Inhibitors↗
Anaphylactic reaction to epidural fentanyl.
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Adult↗
The effects of local anesthetics on maternal and neonatal platelet function.
The effects of bupivacaine (B), lidocaine (L) and 2-chloroprocaine (C) on maternal (M) and neonatal (N) platelet function were studied using in vitro beta-thromboglobulin (beta-tg) release (radioimmunoassay), and in vitro platelet aggregation. Aggregation produced by adenosine diphosphate (ADP), epinephrine and collagen was measured in the presence of 1, 10, 100, 500 or 1000 micrograms/ml concentrations of B, L or C. In addition, spontaneous in vivo beta-tg release was measured in M and N blood. In vivo beta-tg level in M and N blood was approximately double that in non-pregnant subjects (p less than 0.025). In vitro beta-tg release in M and N samples was inhibited only at concentrations exceeding 1000 micrograms/ml, and the inhibition was less in M and N samples than in non-pregnant subjects. None of the anesthetics inhibited aggregation of M or N platelets at 1 and 10 micrograms/ml. Only concentrations of 500 micrograms/ml or greater consistently inhibited platelet aggregation produced by the three aggregants in M and N samples, and L was the least effective of the three agents. Neonatal platelet aggregation was affected more by local anesthetics than was maternal aggregation. It is concluded that plasma local anesthetic concentrations achieved during normal maternal epidural anesthesia do not affect M or N platelet aggregation or beta-tg release.
Anesthesia, Epidural↗