MAGNESIUM sulfate and ritodrine have been used for many years to treat preterm labor. Patients receiving magnesium therapy are very sensitive to depolarizing and nondepolarizing neuromuscular blocking drugs. 1The unexpected prolongation of the action of nondepolarizing neuromuscular blocking drugs in patients treated with magnesium has been reported. 2,3Therefore, these patients should not be “pretreated” with a nondepolarizing agent before receiving succinylcholine. 4,5Recently, we encountered three obstetric patients who were treated using continuous intravenous magnesium and ritodrine therapy. Cardiac arrest developed in the first patient and electrocardiographic abnormalities were seen concomitant with hyperkalemia in the others after anesthetic induction of intravenous anesthetics and succinylcholine.
A 34-yr-old woman was transferred to the Japanese Red Cross Nagoya First Hospital at 19 weeks’ 0 days’ gestation. She conceived triplets by in vitro fertilization–embryo transfer and underwent Shirodkar cervical cerclage at 9 weeks’ gestation. Her first episode of vaginal bleeding occurred at 18 weeks’ 5 days’ gestation and she was referred to the hospital because of bleeding and uterine contractions. Results of tests for maternal serum C-reactive protein were positive, and antibiotics and ritodrine (100 μg/min) were started to control chorioamnionitis and uterine contractions. Nevertheless, supplementary administration of magnesium sulfate was necessary. Continuous intravenous administration of magnesium sulfate was started at 22 weeks’ 5 days’ gestation. The infusion rate of magnesium sulfate was adjusted to maintain the total magnesium concentrations in the plasma between 5.5 and 7.5 mg/dl.
Treatment was effective for 5 weeks, but finally the cervix started to open. At 25 weeks’ 3 days’ gestation, a decision was made to deliver one neonate and to try to recerclage the cervix during general anesthesia. The total dose of magnesium sulfate administered until that day was 2,221 g (over 20 days); total magnesium concentration was 9.0 mg/dl; and plasma potassium (K+) and total calcium concentrations were 4.0 mm and 5.9 mg/dl, respectively. Plasma creatine kinase was 4,040 IU/l on that day. She was premedicated with atropine sulfate (0.5 mg) and ranitidine hydrochloride (50 mg) intramuscularly. Anesthesia was induced using sodium thiamylal (250 mg) and succinylcholine (120 mg) intravenously, and the trachea rapidly was intubated. After induction, the patient suddenly became cyanotic and pulseless. The electrocardiography monitor showed ventricular fibrillation. Ventilation with oxygen and external cardiac compression was started immediately. After 45 min of external cardiac compression and intravenous administration of atropine sulfate, lidocaine, bicarbonate, calcium chloride, and epinephrine, the heart was defibrillated successfully on the seventh countershock. During this period, all three infants were delivered vaginally via vacuum delivery, to make it easier to execute cardiopulmonary resuscitation, and were taken care of by the neonatologists. During cardiopulmonary resuscitation, 25 min after the onset of cardiac arrest, arterial blood gas measurement was obtained and was within normal limits (table 1). The serum potassium concentration for that sample was 5.7 mm. After defibrillation, hemodynamics were stable and anesthesia was completed uneventfully. Postoperatively no adverse neurologic or electrocardiographic abnormalities developed.
A 25-yr-old woman with a known twin gestation was admitted to the hospital at 23 weeks’ 6 days’ gestation with the diagnosis of preterm labor. Continuous intravenous administration of magnesium sulfate and ritodrine (200 μg/min) was started for the combined tocolytic action.
At 26 weeks’ 3 days’ gestation, a cesarean section was planned because of the diagnosis of acute fetal distress. The total dose of magnesium sulfate administered until that day was 1,734 g and total magnesium concentration in the plasma was 7.8 mg/dl. Plasma CK was 2,120 IU/l on that day. Consent to the serial measurements of blood electrolytes was obtained before induction of anesthesia. No premedication was administered. Anesthesia was induced using sodium thiamylal (200 mg) and succinylcholine (100 mg) intravenously, and the trachea rapidly was intubated. Whole blood ionized electrolytes were analyzed by use of NOVA Stat Profile Ultra (NOVA Biochemical, Waltham, MA). Within a few minutes of succinylcholine administration, the electrocardiogram showed elevated T waves. The electrocardiographic abnormalities developed rapidly. Two minutes later, a short period of ventricular tachycardia was observed. The K+concentration reached 6.3 mm (table 2). Calcium chloride was injected and the electrocardiogram showed normal QRS complexes and T waves. The remainder of the anesthetic course was uneventful, and the patient’s neurologic condition was unchanged postoperatively.
A 28-yr-old woman with a history of bronchial asthma during childhood was admitted to the hospital at 25 weeks’ 6 days’ gestation with the diagnosis of a twin gestation and preterm labor. The intravenous administration of ritodrine (100 μg/min) was started on the day of admission. Two days later, continuous intravenous administration of magnesium sulfate also was started.
At 28 weeks’ 3 days’ gestation the patient, with the diagnosis of twin–twin transfusion syndrome, was scheduled to undergo cesarean section. The total dose of magnesium sulfate administered since admission was 1,759 g, and total magnesium concentration in the plasma was 5.3 mg/dl. Her plasma CK concentration was 630 IU/l on that day. Informed consent to undergo arterial cannulation and serial measurements of blood electrolytes was obtained before induction of anesthesia. The patient was premedicated with atropine sulfate (0.5 mg) and ranitidine hydrochloride (50 mg) intramuscularly. Anesthesia was induced using ketamine (60 mg) and succinylcholine (120 mg) intravenously, and the trachea rapidly was intubated. Serial electrocardiographic tracings, arterial blood sampling, and blood pressure recordings were performed. Within 2 min of administration of succinylcholine, plasma potassium concentration reached 7.2 mm (table 3) and the electrocardiogram showed widened QRS complexes and elevated T waves. Calcium chloride was injected, and within 10 min, the electrocardiogram showed normal QRS complexes and T waves. The remainder of the anesthetic course was uneventful.
The cardiac arrest seen in patient 1 was unusual because tracheal intubation was performed rapidly and smoothly, and the patient did not show remarkable hemodynamic changes before ventricular fibrillation. She had neither neuromuscular diseases nor severe infections. Arterial blood gas measurements, obtained during cardiopulmonary resuscitation, showed normal arterial blood-gas analysis results and a high potassium concentration. We believe that we excluded most of the common explanations for this type of cardiac arrest, with the exception of transient electrolyte abnormalities. Therefore, we measured the plasma concentrations of electrolytes before and after the induction of anesthesia in patients 2 and 3. Although the concentrations of calcium were low and of magnesium were high throughout the anesthetic induction because of magnesium infusion therapy, there were no remarkable changes in plasma electrolytes, with the exception of the potassium concentrations. Serious hyperkalemia occurred after injection of succinylcholine in patients 2 and 3.
Succinylcholine causes an increase in plasma potassium concentrations up to 1.0 mm; this level peaks within 2–5 min and quickly returns to a baseline value in healthy persons. 6–8This is a result of potassium efflux from skeletal muscles at the neuromuscular junction. Patients with burns, infections, or neuromuscular disease are at risk for massive hyperkalemia after succinylcholine injection. 9One explanation for this phenomena is that extrajunctional acetylcholine receptors have developed in these patients, so that potassium is released from the entire muscle instead of at the neuromuscular junction alone. This increase in potassium release is referred to as up-regulation of acetylcholine receptors. 10
The administration of succinylcholine in immobilized patients may cause hazardous hyperkalemic response. 10All three of our patients were restricted to beds because they received ritodrine and magnesium infusion for 2 to 3 weeks. It is likely that prolonged immobilization or bed rest contributed to the hyperkalemic response after the administration of succinylcholine in these patients.
It also has been reported that prolonged use of nondepolarizing neuromuscular blocking drugs, along with immobilization and disuse atrophy, predisposes the patient to hyperkalemia and cardiac arrest after administration of succinylcholine. 11Continuous subliminal (subparalytic) competitive antagonism of acetylcholine receptors (i.e. , antagonism in the absence of immobilization) can induce a proliferation of acetylcholine receptors. 11Magnesium has a direct depressant effect on skeletal muscle contraction. In addition, excess magnesium decreases acetylcholine release from motor nerve impulses, reduces the sensitivity of the motor end-plate to applied acetylcholine, and decreases the amplitude of the motor end-plate potential. 12We speculate herein that the long-term use of magnesium, with associated immobilization and disuse atrophy, predisposed the patients to cardiac arrest (in patient 1) and severe hyperkalemia (in patients 2 and 3) in response to succinylcholine.
In all our patients, the plasma creatine kinase concentration was increased before anesthetic induction. Although its relation to the administration of magnesium and ritodrine is uncertain, an increased creatine kinase concentration may indicate the degeneration of skeletal muscle cells and predict hyperkalemia after succinylcholine administration.
Ritodrine is a selective β2-adrenergic agonist developed specifically for use as a uterine relaxant. Ritodrine can cause hypokalemia through movement of the potassium ions into the intracellular compartments. Preoperative ritodrine therapy and abrupt cessation just before surgery may have caused an efflux of potassium ions from the intracellular compartments and exaggerated hyperkalemia after succinylcholine.
In conclusion, although succinylcholine is a first-line neuromuscular blocking drug for cesarean section, our experience suggests that succinylcholine should be used with extreme caution in patients who have been immobilized in bed and have had long-term exposure to magnesium and ritodrine.