Laurence S. Reisner

Neurotoxicity of Local Anesthetics: Altered Perineurial Permeability, Edema, and Nerve Fiber Injury

A quantitative, in situ experimental method was developed employing the rat sciatic nerve to study the neurotoxicity of local anesthetic solutions applied directly to an intact peripheral nerve bundle. One-milliliter volumes of 2-chloroprocaine, 3%; tetracaine, 1 %; lidocaine, 2%; bupivacaine, 0.75%; or sodium chloride, 0.2%; were injected with a 30-gauge needle beneath the mesoneurium but exterior to the epineurium. The wound was closed and the animals were normally maintained until the nerves were reexposed for quantitative biophysical and morphologic testing 24 h to 4 weeks later. The results indicate that topically applied 2-chloroprocaine and tetracaine produce significant endoneurial edema 48 h after treatment. Horseradish peroxidase was used to verify increased permeability of the perineurium. Endoneurial fluid pressure was significantly increased in edematous nerves. Electron microscopy revealed abnormal mast cells and proliferation of endoneurial fibro-blasts in addition to Schwann cell injury and axonal dystrophy. This study shows that extrafascicular administration of clinically used concentrations of local anesthetic solutions can alter perineurial permeability, producing changes in the endoneurial environment that are associated with neurotoxic injury. Perineurial and endoneurial fibrolic changes may be a late consequence of peripheral nerve injury with anesthetic solutions producing altered perineurial permeability with endoneurial edema.

Successful pregnancy after cardiac transplantation

Summary A case report of a successful pregnancy after cardiac allotransplantation is presented. The patient underwent transplantation for an inoperable cardiac tumor 5 years before conception. Cardiac function before and during all stages of pregnancy was normal. Maintenance immunosuppressive therapy consisting of prednisone and azathioprine was continued through gestation. The pregnancy was complicated by a primary herpes virus infection requiring parenteral acyclovir treatment and a single episode of preterm labor that was successfully treated. The infant was born at term, weighed 3278 gm, and has developed normally during the first 3 years of life. The patient died 5 months after delivery as a result of an acute immunologic rejection 5 months post partum caused by self-initiated discontinuation of immunosuppressive therapy. Preconceptional counseling and pregnancy care guidelines are discussed. (Am J Obstet Gynecol 1989;160:367-71.)

Evaluation of the use of continuous lumbar epidural anesthesia for hypertensive pregnant women in labor

The use of continuous lumbar epidural anesthesia in women with pregnancy-induced hypertension remains controversial. We retrospectively reviewed the charts of 285 women with pregnancy-induced hypertension who were delivered in a 2-year period. Among 185 vaginally delivered patients who received continuous lumbar epidural or local anesthesia, there were no significant differences in the incidence of maternal hypotension, abnormal fetal heart rate tracings, low Apgar scores, or neonatal intensive care unit admissions. Of 100 patients delivered by cesarean section, the incidence of low Apgar scores, depressed umbilical cord pH values, and neonatal intensive care unit admission was increased among those who received general anesthesia (p less than 0.05). However, general anesthesia patients were more likely to have abnormal fetal heart rate tracings (27% versus 4%) requiring urgent delivery. Thus differences in outcome probably reflect poorer fetal condition prior to anesthesia induction rather than a specific anesthetic effect. These results demonstrate that continuous lumbar epidural anesthesia is safe and effective for both the fetus and the mother with pregnancy-induced hypertension.

The Role of 2-Chloroprocaine and Sodium Bisulfite in Rat Sciatic Nerve Edema

In order to evaluate the possible mechanisms of local anesthetic toxicity, the rat sciatic nerve was exposed to various solutions including Nesacaine (containing the antioxidant sodium bisulfite), 2-chloroprocaine in the Nesacaine vehicle (0.2% sodium chloride), 0.2% sodium bisulfite in 0.2% sodium chloride, or 0.2% sodium chloride alone. All solutions were pH balanced between 2.9 and 3.2. Forty-eight hours (h) following extraneural administration of 1 ml volumes, significant edema was produced by all solutions containing 3% 2-chloroprocaine, but not with 0.2% bisulfite in sodium chloride or with sodium chloride alone. Intrafascicular administration of five to ten microliter volumes of these solutions produced edema at 48 h in all cases, but the highest levels were observed with Nesacaine and the lowest levels with 0.2% bisulfite. The results of this study implicate the local anesthetic 2-chloroprocaine in the production of nerve edema, which is inconsistent with other reports that the toxicity of Nesacaine-CE can be attributed to the antioxidant bisulfite.

Anesthetic management of the parturient with fever and infection

Fever is a common clinical problem in labor and delivery suites. It can result from a variety of infectious microorganisms, tissue trauma, malignancy, drug administration, and endocrine and immunologic disorders. Infection is the most common cause of fever, reflecting the effect of pyrogens on the hypothalamus. The diagnosis of infection in pregnancy often raises questions about the safety of regional anesthesia in febrile patients. Despite this concern, and lack of universal guidelines, it has now been well established that the presence of infection and fever in labor does not always contraindicate the administration of regional anesthesia.

Life-threatening effects of intravascular absorption of PGF2 alpha during therapeutic termination of pregnancy.

A case of inadvertent intravascular injection of PGF2alpha during induction of labor by intraamniotic injection for fetal demise involving alternating extreme hypotension and hypertension is described. The woman was a 29-year old in late 2nd trimester with oligohydramnios but no other related history. She was given epidural anesthesia 7.5 mg midazolam and 5 mg morphine S04 for anxiety. Because of oligohydramnios 300 ml Ringers lactate was instilled to dilute the PG. A test dose of 1 mg PGF2alpha was tolerated well. 80 g urea and 20 mg PGF2alpha were injected over 10 minutes. A few minutes later contractions began followed by complaints of burning on face and chest and dyspnea. Oxygen was given by mask. Systolic pressure fell to 70 mm by cuff; peripheral pulses could not be palpated but the patient remained alert and oriented. She was given 35 mg ephedrine and increased iv fluids. She remained dyspneic her extremities became mottled and she complained of chest pressure severe headache and severe breast tenderness. Blood pressure rose to 220/135 mm Hg; pulse to 95 and respiratory rate to 44. Pulse oximetry detectable at the earlobe only was 94% saturation. After 50 mg labetalol blood pressure fell to 134/77 but symptoms remained. For 2 hours blood pressure swung between 76/50 and 225/125 until delivery of the fetus. An arterial line could not be started because of extreme vasoconstriction. Central venous pressure was 13 cm H20. After artificial rupture of the membranes and removal of remaining PG blood pressure stabilized. Delivery was accomplished without incident. The symptoms and labile blood pressure were considered to be due to intravascular injection of PGF2alpha caused by repeated bolus injection at each uterine contraction. In case of PG induction for fetal demise it is recommended that anesthesiologists be prepared to treat intravascular collapse hypertension and bronchoconstriction.

Life-Threatening Effects of Intravascular Absorption of PGF2 During Therapeutic Termination of Pregnancy

A case of inadvertent intravascular injection of PGF2alpha during induction of labor by intraamniotic injection for fetal demise, involving alternating extreme hypotension and hypertension, is described. The woman was a 29-year old in late 2nd trimester with oligohydramnios, but no other related history. She was given epidural anesthesia, 7.5 mg midazolam and 5 mg morphine S04 for anxiety. Because of oligohydramnios, 300 ml Ringers lactate was instilled to dilute the PG. A test dose of 1 mg PGF2alpha was tolerated well. 80 g urea and 20 mg PGF2alpha were injected over 10 minutes. A few minutes later contractions began, followed by complaints of burning on face and chest and dyspnea. Oxygen was given by mask. Systolic pressure fell to 70 mm by cuff; peripheral pulses could not be palpated, but the patient remained alert and oriented. She was given 35 mg ephedrine and increased iv fluids. She remained dyspneic, her extremities became mottled, and she complained of chest pressure, severe headache and severe breast tenderness. Blood pressure rose to 220/135 mm Hg; pulse to 95, and respiratory rate to 44. Pulse oximetry, detectable at the earlobe only, was 94% saturation. After 50 mg labetalol, blood pressure fell to 134/77, but symptoms remained. For 2 hours blood pressure swung between 76/50 and 225/125, until delivery of the fetus. An arterial line could not be started because of extreme vasoconstriction. Central venous pressure was 13 cm H20. After artificial rupture of the membranes and removal of remaining PG, blood pressure stabilized. Delivery was accomplished without incident. The symptoms and labile blood pressure were considered to be due to intravascular injection of PGF2alpha, caused by repeated bolus injection at each uterine contraction. In case of PG induction for fetal demise, it is recommended that anesthesiologists be prepared to treat intravascular collapse, hypertension and bronchoconstriction.