Mieczyslaw Finster

The Apgar Score Has Survived the Test of Time

In 1953, Virginia Apgar, M.D. published her proposal for a new method of evaluation of the newborn infant. The avowed purpose of this paper was to establish a simple and clear classification of newborn infants which can be used to compare the results of obstetric practices, types of maternal pain relief and the results of resuscitation. Having considered several objective signs pertaining to the condition of the infant at birth she selected five that could be evaluated and taught to the delivery room personnel without difficulty. These signs were heart rate, respiratory effort, reflex irritability, muscle tone and color. Sixty seconds after the complete birth of the baby a rating of zero, one or two was given to each sign, depending on whether it was absent or present. Virginia Apgar reviewed anesthesia records of 1025 infants born alive at Columbia Presbyterian Medical Center during the period of this report. All had been rated by her method. Infants in poor condition scored 0-2, infants in fair condition scored 3-7, while scores 8-10 were achieved by infants in good condition. The most favorable score 1 min after birth was obtained by infants delivered vaginally with the occiput the presenting part (average 8.4). Newborns delivered by version and breech extraction had the lowest score (average 6.3). Infants delivered by cesarean section were more vigorous (average score 8.0) when spinal was the method of anesthesia versus an average score of 5.0 when general anesthesia was used. Correlating the 60 s score with neonatal mortality, Virginia found that mature infants receiving 0, 1 or 2 scores had a neonatal death rate of 14%; those scoring 3, 4, 5, 6 or 7 had a death rate of 1.1%; and those in the 8-10 score group had a death rate of 0.13%. She concluded that the prognosis of an infant is excellent if he receives one of the upper three scores, and poor if one of the lowest three scores.

Bupivacaine Toxicity in Pregnant and Nonpregnant Ewes

The relative central nervous system and cardiovascular toxicity of bupivacaine was compared in pregnant and nonpregnant ewes during continuous infusion of bupivacaine into the jugular vein at the rate of 0.5 mg. kg-1. min-1. In all animals, identical symptoms of toxicity occurred in the following order: convulsions, hypotension, respiratory arrest, and circulatory collapse. The dose of bupivacaine required to produce central nervous system (CNS) toxicity in the pregnant ewe tended to be lower than in the nonpregnant animal, although the difference was not statistically significant (P < 0.1). However, the mean dose of bupivacaine resulting in cardiovascular collapse was significantly lower in pregnant ewes (5.1 ± 0.7 mg/kg) than in nonpregnant animals (8.9 ± 0.9 mg/kg). Similarly, bupivacaine blood concentrations at the onset of respiratory arrest and circulatory collapse were lower in the pregnant group, being 5.2 ± 0.7 μg/ml and 5.5 ± 0.8 μg/ml, respectively, versus 7.5 ± 1.0 μg/ml and 8.0 ± 0.9 μg/ml, respectively, in the nonpregnant group (P < 0.05). The concentration of bupivacaine in the brain of pregnant ewes at the time of cardiovascular collapse was significantly lower (P < 0.01) than in the nonpregnant group (7.5 ± 1.5 vs. 16.3 ± 1.7 μg/g). The myocardial tissue concentration of bupivacaine also tended to be lower in the pregnant group, although the differences were not statistically significant (P < 0.1). Comparisons of bupivacaine doses and blood concentrations associated with the onset of convulsions and circulatory collapse (CC/CNS ratio) with those of lidocaine, reported previously, indicate that a narrower margin of safety exists following administration of bupivacaine in nonpregnant sheep. These ratios were 3.7 ± 0.5 and 1.6 ± 0.1, respectively, for bupivacaine and 7.1 ± 1.1 and 3.6 ± 0.3, respectively, for lidocaine. In addition, the data indicate that the pregnant sheep may be more sensitive to the cardiotoxic effects of bupivacaine than the nonpregnant animal.

Comparative systemic toxicity of ropivacaine and bupivacaine in nonpregnant and pregnant ewes.

Background Ropivacaine is a new amide local anesthetic, having therapeutic properties similar to those of bupivacaine but with a wider margin of safety. Bupivacaine is probably the most commonly used drug in obstetric epidural analgesia, even though laboratory studies have suggested that pregnancy increases the cardiotoxicity of bupivacaine but not of other local anesthetics. The current study was designed to reevaluate, in a random and blinded fashion, the systemic toxicity of bupivacaine and ropivacaine in nonpregnant and pregnant sheep. Methods Chronically prepared nonpregnant and pregnant ewes were randomized to receive an intravenous infusion of ropivacaine or bupivacaine at a constant rate of 0.5 mg *symbol* kg sup ‐1 *symbol* min sup ‐1 until circulatory collapse. The investigators were blinded to the identity of local anesthetic. Heart rate, arterial blood pressure, and cardiac rhythm were monitored throughout the study. Arterial blood samples were obtained before infusion and at the onset of toxic manifestations, which appeared in the following sequence: convulsions, hypotension, apnea, and circulatory collapse. Serum drug concentrations and protein binding were determined. Blood pH and gas tensions were measured. Results There were no significant differences between nonpregnant and pregnant animals in the doses or serum concentrations of either drug required to elicit toxic manifestations. In nonpregnant animals, similar doses and serum concentrations of ropivacaine and bupivacaine were associated with the onset of convulsions and circulatory collapse. In pregnant ewes, greater doses of ropivacaine as compared to bupivacaine were required to produce convulsions (7.5 plus/minus 0.5 vs. 5.0 plus/minus 0.6 mg *symbol* kg sup ‐1) and circulatory collapse (12.9 plus/minus 0.8 vs. 8.5 plus/minus 1.2 mg *symbol* kg sup ‐1). The corresponding serum concentrations of ropivacaine were similar to those of bupivacaine. Pregnancy did not affect the serum protein binding of either drug. The proportion of animals manifesting a malignant ventricular arrhythmia as the terminal event was similar among all groups. Conclusions The systemic toxicity of ropivacaine or bupivacaine is not enhanced by gestation in sheep. This is in contrast to an earlier study in which the cardiotoxicity of bupivacaine was enhanced during ovine pregnancy. Greater doses of ropivacaine, as compared to bupivacaine, are needed to produce toxic manifestations in pregnant animals.

Transmission of Mepivacaine Hydrochloride (Carbocaine) Across the Human Placenta

Transmission of mepivacaine hydrochloride (Carbocaine) across the placenta was studied in 56 healthy women at term who received epidural analgesia during labor and delivery. All infants were delivered vaginally. Concentrations of mepivacaine were determined in maternal and umbilical cord blood by the methyl orange method. Mepivacaine administered into the maternal epidural space passed rapidly into the blood stream and crossed the placenta. Five mothers who received repeated injections, developed toxic symptoms; concentrations of the drug in blood were significantly higher than those in patients without complications. Twelve infants were depressed at birth; in 5, blood levels of the drug were significantly higher than those found in vigorous babies.

Incidence of visceral pain during cesarean section: the effect of varying doses of spinal bupivacaine

The safety of 0.5% hyperbaric bupivacaine, as well as the incidence and severity of visceral pain, were evaluated in 36 women undergoing elective cesarean section under spinal anesthesia who, randomly divided into two groups, received different dose ranges according to height, 7.5-10 mg in group A and 10-12.5 mg in group B. When sensory block to at least the fourth thoracic dermatome was established, surgery was begun and the occurrence and severity of visceral pain recorded (visual analog scale) by an observer unaware of patient data. The level of analgesia to pinprick was determined when and if there was onset of pain intraoperatively, and supplementary medication was administered as needed. Hypotension, the incidence of which was similar in both groups, was treated as necessary with ephedrine. No patients experienced pain until after delivery of the infant. Thereafter, moderate to severe pain, in association with peritoneal traction, occurred in 12 patients in group A (70.5%) but only in 6 patients in group B (31.6%). In patients experiencing moderate to severe pain, the mean time between induction of anesthesia and onset of pain was similar in both groups, as was the amount of systemic narcotic given. Total time for regression of sensory analgesia to L5 was longer in patients in group B (243.9 versus 195.4 min), and the incidence of complete motor blockade was greater in group B. Increasing the amount of 0.5% hyperbaric bupivacaine per spinal segment reduces the occurrence of moderate to severe visceral pain during elective cesarean section without jeopardizing mother or fetus.

Hyperbaric Bupivacaine for Spinal Anesthesia in Cesarean Section

The efficacy and safety of 0.5% hyperbaric bupivacaine (Sensorcaine, Astra) was evaluated in 22 patients undergoing elective cesarean section under spinal anesthesia. The dose varied from 7.5 to 10 mg, (depending on the patients height) which was significantly lower than previously reported. Patients were placed in head-down tilt immediately after sub-arachnoid injection. The mean spread of analgesia was to T3, which was reached in 10–15 min. Regression was complete in 258 ± 16 min. Complete motor paralysis of lower extremities occurred in only two patients. Complete recovery of motor function in all patients was evident in less than 2.5 h. All infants were vigorous at birth and there were no serious maternal complications. The incidence of hypotension was 4.5%, the lowest reported as a consequence of spinal anesthesia in this group of patients, A technique involving the use of reduced doses of hyperbaric bupivacaine (0.5%) in conjunction with head-down tilt appears to be useful for spinal anesthesia for cesarean section.

Tissue Thiopental Concentrations in the Fetus and Newborn

The distribution of thiopental was studied in tissues and organs of anencephalic human neonates and in fetal guinea pigs. The drug was administered by intermittent intravenous injections to the mother or by a single injection into the guinea pig fetus via the umbilical vein. High concentrations were found in the fetal liver, especially following direct injection into the fetus, in which case as much as 50 per cent of the dose could be accounted for in this organ. These findings document the importance of the fetal liver in preventing the fetal brain from being exposed to high concentrations of thiopental administered to the mother.

Systemic toxicity of ropivacaine during ovine pregnancy.

Ropivacaine is a new amide local anesthetic structurally related to bupivacaine and mepivacaine. Its potency and duration of action are similar to those of bupivacaine but its therapeutic index may be greater. Since pregnancy enhances the cardiotoxicity of bupivacaine, the current study was devised to compare the toxicity of ropivacaine in chronically instrumented nonpregnant and pregnant ewes during continuous intravenous infusion of the drug at the rate of 0.5 mg.kg-1.min-1. In all animals, symptoms of local anesthetic toxicity occurred in the usual order--convulsions, hypotension, apnea, and circulatory collapse. There were no significant differences between the two groups of animals in the doses and plasma concentrations of ropivacaine associated with each toxic manifestations. For example, circulatory collapse occurred at a mean dose of 11.3 +/- 1.1 mg.kg-1 in nonpregnant and 12.4 +/- 0.9 mg.kg-1 in pregnant animals, with corresponding plasma concentrations of 7.3 +/- 0.3 and 9.6 +/- 2.1 micrograms.ml-1 (P = not significant). Protein binding of ropivacaine in the concentration range associated with toxic manifestations was similar in sera obtained from nonpregnant and pregnant ewes. In conclusion, ovine pregnancy does not enhance the systemic toxicity of ropivacaine, possibly because of an absence of gestation-related increase in the availability of free drug.

Accidental intoxication of the fetus with local anesthetic drug during caudal anesthesia

Abstract Accidental intoxication with mepivacaine (a local anesthetic drug) occurred in 4 infants as a complication of attempted caudal anesthesia. All infants were depressed at birth and convulsed after artificial ventilation had been instituted. Two of the infants survived following respirator treatment, exchange transfusion, and gastric lavage.

Adverse Effects of Maternally Administered Lidocaine on the Asphyxiated Preterm Fetal Lamb

Lidocaine was infused at a constant rate of 0.1 mg.kg-1.min-1 for 180 min into 12 chronically prepared pregnant sheep while asphyxia, induced by partial umbilical cord occlusion, was maintained in the premature fetus (80% of gestation). In five similar preparations saline instead of lidocaine was infused into the mother for 180 min. Maternal and fetal arterial blood pressure, heart rate, pHa, PaCO2, and PaO2 were monitored, and fetal cardiac output and the distribution of blood flow to fetal organs were measured, using labeled microspheres, before and after asphyxia and again after maternal infusion of lidocaine or saline. Maternal and fetal arterial blood and maternal urine were obtained at intervals for determination of lidocaine concentrations and urinary drug clearance. At the end of infusion, these animals were killed and tissues dissected for determination of lidocaine concentrations and organ blood flow. Maternal and fetal lidocaine plasma concentrations at steady state were 2.32 +/- 0.12 and 1.23 +/- 0.17 microgram/ml, respectively, similar to those seen during human epidural anesthesia. Asphyxia resulted in a significant drop in fetal heart rate and increased blood flow to the brain, heart, and adrenals. Asphyxia and saline did not produce additional deterioration of the fetus, but asphyxia and lidocaine led to a significant increase in PaCO2 and decreases in pHa, mean arterial pressure, and blood flows to the brain, heart, and adrenals. It is concluded that the immature fetus loses its cardiovascular adaptation to asphyxia when exposed to clinically acceptable plasma concentrations of lidocaine obtained transplacentally from the mother.