Int J Gynaecol Obstet 17: 250-252, 1979
Hyponatremic Fits in Oxytocin-Augmented Labors P. McKenna and R. W. Shaw Department of Obstetrics and Gynaecology, Birmingham Maternity Hospital, Edgbaston, Birmingham, England
ABSTRACT McKenna P, Shaw R W (Dept of Obstetrics and Gynaecology, Birmingham Maternity Hospital, Edgbaston, Birmingham, England). Hyponatremic fits in oxytocin-augmented labors. IntJ Gynaecol Obstet 17: 250-252, 1979 Case reports of three patients who hadfits as a consequence of hyponatremia are presented. Each patient was in spontaneous labor at term and received conventional doses of oxytocin for augmentation. The pathogenesis, diagnosis and treatment of this entirely iatrogenic condition are discussed. The differences between these and similar cases in the literature are stressed.
INTRODUCTION Water intoxication associated with oxytocin infusion has been frequently reported. T h e circumstances of its occurrence varied. They included the treatment of missed abortion (6), management of incomplete abortion and treatment of postpartum hemorrhage (8, 10) and in association with midtrimester pregnancy termination (4, 7). It has also been reported once with induction of labor (3) and once with augmentation of uterine activity after spontaneous rupture of the membranes (9). In the latter case, large doses of buccal oxytocin citrate (Pitocin Citrate, Parke, Davis & Co, Detroit, M I , USA) were given in addition to intravenous oxytocin, thus differing from what is now the conventional management of labor. CASE R E P O R T S Case 1 Case 1, a healthy 18-year-old married primigrávida, was admitted in spontaneous labor at 39 weeks' gestation. When her cervix was 3 cm dilated, her
IntJ Gynaecol Obstet 17
membranes were ruptured and a scalp electrode and intrauterine pressure catheter were inserted. T w o hours later cervical dilation was 4 cm, and stimulation with 2 m U / m i n of oxytocin was begun. Dosage was increased stepwise to 10 m U / m i n . Dilation was slow, but after 11 hours in labor the patient was 9 cm dilated. T h e cervix remained at 9cm dilation for three hours, during which time fetal blood was sampled (pH = 7.28 and 7.29). T h e fetal heart rate remained normal throughout. After three hours at 9-cm dilation, with the vertex still two-fifths palpable through the abdomen, it was decided to deliver by lower segment cesarean section. O n the way to the operating theater, the patient had a grand mal fit that was controlled by intravenous (IV) diazepam (Valium, Roche Laboratories, Nutley, NJ, USA). Her blood pressure immediately before the fit was normal, and there was no proteinuria. A lower segment cesarean section was carried out, and a 3.5-kg male infant was delivered. T h e infant required intubation for 11 minutes. His one- and five-minute Apgar scores were 4 and 4, respectively. T h e infant had one cyanotic attack and a convulsion four hours after birth. Infection was ruled out as a cause, and the infant's subsequent course was uneventful. He was discharged as normal from the follow-up clinic at one year. T h e mother was sedated, and a review of her fluid balance showed that she had had an input of 5 liters of 5% dextrose in water in the 15 hours before the fit. During this time, she had a total urinary output of 900 ml, of which 650 ml was during the first six hours of labor. T h e total dosage of oxytocin was less than 15 IU. At the time of the fit, her serum levels were urea, 2.8 mmole/liter; sodium, 114.0 mmole/liter: and potassium, 3.3 mmole/liter. Urea a n d electrolyte levels reverted to normal and the patient m a d e a full recovery within 24 hours. An EEG m a d e during the puerperium was normal.
Hyponatremic fits in labor
Case 2 Case 2 was a healthy 21-year-old married primigrávida who was admitted in spontaneous labor at 39 weeks' gestation. T h e patient was admitted for rest at 37 and 38 weeks' gestation because of mild gestational hypertension. The membranes were ruptured and stimulation with oxytocin begun after three hours of labor. After 16 hours in labor, when the patient was 9 cm dilated, she had a fit. Her blood pressure was 130/ 80 mm Hg, with no proteinuria. T h e suspected diagnosis of hyponatremia was confirmed by serum sodium of 121.0 mmole/liter, potassium of 3.1 mmole/liter and urea of 2.7 mmole/liter. The patient was allowed to labor and was eventually delivered by forceps some four hours later of a 3.02-kg male infant, with one- and five-minute Apgar scores of 9 and 10, respectively. This patient had an IV fluid intake before the fit of 6 liters of 5% dextrose in water, with a urinary output of 900 ml. T h e serum urea and electrolytes were normal within 24 hours, and the mother recovered totally. At a neurologic consultation six weeks later, it was not thought necessary to perform an E E C Case 3 Case 3, a healthy 30-year-old primigrávida, was admitted in spontaneous labor at term. Her membranes were ruptured, the fetus was monitored, and labor was augmented with oxytocin. T h e initial oxytocin dosage of 2 m U / m i n rose to 10 m U / m i n . At 9-cm cervical dilation, there was secondary arrest for three hours and the fetal head remained twofifths palpable through the abdomen. After delivery by cesarean section, the 2.74-kg male infant had one- and five-minute Apgar scores of 1 and 5, respectively. T h e infant did not establish spontaneous respirations for 20 minutes, but his subsequent neonatal behavior was surprisingly normal. Six hours postpartum, the mother had a grand mal-type seizure.
Table I. Summary of intravenous fluid and urinary hyponatremic fits in augmented labors. 5% Dextrose in Water Volume (ml)
Case
Duration of Infusion (hours)
Urine Volume (ml)
í
í~5
5000
900
2 3
16 16
6000 6800
900 500
251
After her fluid chart during labor and postdelivery was reviewed, the diagnosis was apparent a n d was confirmed by the serum chemistry (sodium, 112.0 mmole/liter; potassium, 3.8 mmole/liter; urea, 2.1 mmole/liter). Before lower segment cesarean section was performed, the patient had an intake of 4.0 liters of 5% dextrose in water, and, in the six hours after cesarean section, she had an intake of 2.8 liters of 5% dextrose in water. During this 16hour period, her output h a d been about 500 ml of urine. Over the next 24 hours, the patient had a diuresis of 6 liters, and her neurologic recovery, although eventually complete, was very slow, eg, her speech was quite slurred for about four days. An EEG m a d e during the puerperium was normal. Relevant data on the three patients are summarized in Table I. DISCUSSION Hyponatremic fits associated with water intoxication and oxytocin infusion are well recognized in obstetric and gynecologic practice. Although there is a superficial resemblance between previously reported cases and the three reported here, there are several important differences. First, the dosage of oxytocin in these three patients is much smaller (maximum = 15 IU). Second, although the volume of fluid given to these patients was similar to that already reported, it was given in a much shorter time. Because these differences are so great, it is possible to argue that the hyponatremia was merely a result of water intoxication a n d h a d nothing to do with oxytocin infusion or, indeed, pregnancy. This is unlikely because oxytocin begins to exert its antidiuretic effect at very small doses (2-5 m U / m i n ) , and there is an individual sensitivity to the antidiuretic effect of oxytocin (1). Whether the fall in serum sodium is greater than can be accounted for by the retention of water alone (7) is difficult to say as the original serum sodium is not known in any of these cases.
and oxytocin dosage in three subjects with Rate of Oxytocin Infusion (mU/min)
Dosage of Oxytocin (IU)
Serum Sodium (mmole/liter)
2-10 2-4 2-10
1~5 10 12
ÏÏ4 121 112
InlJ Gynaecol Obstei 17
252
McKenna and Shaw
Whether the stress of spontaneous labor with small doses of exogenous oxytocin and pethidine (5) combined to produce an antidiuretic response with a resultant greater decrease in the serum sodium than could be expected from dilution alone is largely irrelevant to the point of reporting these three cases. T h e point of these cases is that they each were initially quite healthy a n d then were given a lifeendangering problem of iatrogenic origin. T h e fault was m a d e all the worse by the IV administration of 5% dextrose in water in volumes far in excess of requirements. T h e diagnosis of hyponatremia is based on an awareness that a fit might be due to this problem. Clinically, the patient is usually normotensive with no proteinuria and has some edema. Although not easy to spot in a laboring patient, alteration in levels of consciousness was retrospectively noted in two of our three patients. Electrolyte measurements then confirmed the diagnosis of hyponatremia. T h e subsequent treatment that these patients received included: (a) stopping the fits a n d ensuring the availability of basic life-support measures; (b) stopping the insult, ie, stopping dextrose in water and oxytocin; and (c) resisting the temptation to give a diuretic (instead slowly giving normal saline and considering giving hypertonic saline) (2). Prevention of hyponatremia entails the possible revision a n d adequate supervision of existing fluid administration regimens in delivery suites. As a rule, no more than 2 liters of 5% dextrose in water, the traditional intravenous fluid given to women in labor, should be given in any one labor and certainly no more bottles should be erected without medical reassessment of the patient. Since a retrospective review of labor charts shows that other patients have also received similar quantities of intravenous fluids in normal or prolonged
IntJ Gynaecol Obstet 17
labors, the occurrence of fits in these three cases could suggest a susceptibility to oxytocin.
REFERENCES 1. Abdull-Karim R, Assali N S : Effects of oxytocin on renal haemodynamics a n d water a n d electrolyte excretion. J L a b Clin Med 57:522, 1961. 2. A h m a d AJ, Clark E M , Jacobs M S : W a t e r intoxication associated with oxytocin infusion. Postgrad M e d J 5/:249, 1975. 3. Burt R L , Oliver K L , W h i t n e r DL: W a t e r intoxication complicating elective induction of labour at term. Obstet Gynecol 3*212, 1969. 4. Lauersen U H , Birnbaum SJ: W a t e r intoxication associated with oxytocin administration during saline induced abortion. Am J Obstet Gynecol 121:2, 1975. 5. Liggins G C : Antidiuretic effect of oxytocin, morphine a n d pethidine in pregnancy and labour. Aust N Z J Obstet Gynaecol 3:81, 1963. 6. Liggins G C : T r e a t m e n t of missed abortion by high dosage Syntocinon intravenous infusion. J Obstet Gynaecol Br C o m m o n w 69:211, 1962. 7. M o r g a n DB, Kirwan NA, Hancock K W , Robinson D, A h m a d S: W a t e r intoxication and oxytocin infusion. Br J Obstet Gynaecol 84:6, 1977. 8. S h i p m a n K H , Sitprija V, Holmes S H : Syntocinon in the diagnosis of acute oliguria. Obstet Gynecol 2.3:242, 1969. 9. Storch H S : Acute water retention associated with continuous slow infusion of oxytocin. Obstet Gynecol 37:109, 1971. 10. Whalley PJ, Pritchard J : Oxytocin and water intoxication. J A M A 756:601, 1963.
Address for reprints: Ft. W. Shaw Dept of Obstetrics and Gynaecology Birmingham Maternity Hospital Edgbaston, Birmingham, B15 2TG England
Hyponatremic Fits in Oxytocin-Augmented Labors P. McKenna and R. W. Shaw Department of Obstetrics and Gynaecology, Birmingham Maternity Hospital, Edgbaston, Birmingham, England
ABSTRACT McKenna P, Shaw R W (Dept of Obstetrics and Gynaecology, Birmingham Maternity Hospital, Edgbaston, Birmingham, England). Hyponatremic fits in oxytocin-augmented labors. IntJ Gynaecol Obstet 17: 250-252, 1979 Case reports of three patients who hadfits as a consequence of hyponatremia are presented. Each patient was in spontaneous labor at term and received conventional doses of oxytocin for augmentation. The pathogenesis, diagnosis and treatment of this entirely iatrogenic condition are discussed. The differences between these and similar cases in the literature are stressed.
INTRODUCTION Water intoxication associated with oxytocin infusion has been frequently reported. T h e circumstances of its occurrence varied. They included the treatment of missed abortion (6), management of incomplete abortion and treatment of postpartum hemorrhage (8, 10) and in association with midtrimester pregnancy termination (4, 7). It has also been reported once with induction of labor (3) and once with augmentation of uterine activity after spontaneous rupture of the membranes (9). In the latter case, large doses of buccal oxytocin citrate (Pitocin Citrate, Parke, Davis & Co, Detroit, M I , USA) were given in addition to intravenous oxytocin, thus differing from what is now the conventional management of labor. CASE R E P O R T S Case 1 Case 1, a healthy 18-year-old married primigrávida, was admitted in spontaneous labor at 39 weeks' gestation. When her cervix was 3 cm dilated, her
IntJ Gynaecol Obstet 17
membranes were ruptured and a scalp electrode and intrauterine pressure catheter were inserted. T w o hours later cervical dilation was 4 cm, and stimulation with 2 m U / m i n of oxytocin was begun. Dosage was increased stepwise to 10 m U / m i n . Dilation was slow, but after 11 hours in labor the patient was 9 cm dilated. T h e cervix remained at 9cm dilation for three hours, during which time fetal blood was sampled (pH = 7.28 and 7.29). T h e fetal heart rate remained normal throughout. After three hours at 9-cm dilation, with the vertex still two-fifths palpable through the abdomen, it was decided to deliver by lower segment cesarean section. O n the way to the operating theater, the patient had a grand mal fit that was controlled by intravenous (IV) diazepam (Valium, Roche Laboratories, Nutley, NJ, USA). Her blood pressure immediately before the fit was normal, and there was no proteinuria. A lower segment cesarean section was carried out, and a 3.5-kg male infant was delivered. T h e infant required intubation for 11 minutes. His one- and five-minute Apgar scores were 4 and 4, respectively. T h e infant had one cyanotic attack and a convulsion four hours after birth. Infection was ruled out as a cause, and the infant's subsequent course was uneventful. He was discharged as normal from the follow-up clinic at one year. T h e mother was sedated, and a review of her fluid balance showed that she had had an input of 5 liters of 5% dextrose in water in the 15 hours before the fit. During this time, she had a total urinary output of 900 ml, of which 650 ml was during the first six hours of labor. T h e total dosage of oxytocin was less than 15 IU. At the time of the fit, her serum levels were urea, 2.8 mmole/liter; sodium, 114.0 mmole/liter: and potassium, 3.3 mmole/liter. Urea a n d electrolyte levels reverted to normal and the patient m a d e a full recovery within 24 hours. An EEG m a d e during the puerperium was normal.
Hyponatremic fits in labor
Case 2 Case 2 was a healthy 21-year-old married primigrávida who was admitted in spontaneous labor at 39 weeks' gestation. T h e patient was admitted for rest at 37 and 38 weeks' gestation because of mild gestational hypertension. The membranes were ruptured and stimulation with oxytocin begun after three hours of labor. After 16 hours in labor, when the patient was 9 cm dilated, she had a fit. Her blood pressure was 130/ 80 mm Hg, with no proteinuria. T h e suspected diagnosis of hyponatremia was confirmed by serum sodium of 121.0 mmole/liter, potassium of 3.1 mmole/liter and urea of 2.7 mmole/liter. The patient was allowed to labor and was eventually delivered by forceps some four hours later of a 3.02-kg male infant, with one- and five-minute Apgar scores of 9 and 10, respectively. This patient had an IV fluid intake before the fit of 6 liters of 5% dextrose in water, with a urinary output of 900 ml. T h e serum urea and electrolytes were normal within 24 hours, and the mother recovered totally. At a neurologic consultation six weeks later, it was not thought necessary to perform an E E C Case 3 Case 3, a healthy 30-year-old primigrávida, was admitted in spontaneous labor at term. Her membranes were ruptured, the fetus was monitored, and labor was augmented with oxytocin. T h e initial oxytocin dosage of 2 m U / m i n rose to 10 m U / m i n . At 9-cm cervical dilation, there was secondary arrest for three hours and the fetal head remained twofifths palpable through the abdomen. After delivery by cesarean section, the 2.74-kg male infant had one- and five-minute Apgar scores of 1 and 5, respectively. T h e infant did not establish spontaneous respirations for 20 minutes, but his subsequent neonatal behavior was surprisingly normal. Six hours postpartum, the mother had a grand mal-type seizure.
Table I. Summary of intravenous fluid and urinary hyponatremic fits in augmented labors. 5% Dextrose in Water Volume (ml)
Case
Duration of Infusion (hours)
Urine Volume (ml)
í
í~5
5000
900
2 3
16 16
6000 6800
900 500
251
After her fluid chart during labor and postdelivery was reviewed, the diagnosis was apparent a n d was confirmed by the serum chemistry (sodium, 112.0 mmole/liter; potassium, 3.8 mmole/liter; urea, 2.1 mmole/liter). Before lower segment cesarean section was performed, the patient had an intake of 4.0 liters of 5% dextrose in water, and, in the six hours after cesarean section, she had an intake of 2.8 liters of 5% dextrose in water. During this 16hour period, her output h a d been about 500 ml of urine. Over the next 24 hours, the patient had a diuresis of 6 liters, and her neurologic recovery, although eventually complete, was very slow, eg, her speech was quite slurred for about four days. An EEG m a d e during the puerperium was normal. Relevant data on the three patients are summarized in Table I. DISCUSSION Hyponatremic fits associated with water intoxication and oxytocin infusion are well recognized in obstetric and gynecologic practice. Although there is a superficial resemblance between previously reported cases and the three reported here, there are several important differences. First, the dosage of oxytocin in these three patients is much smaller (maximum = 15 IU). Second, although the volume of fluid given to these patients was similar to that already reported, it was given in a much shorter time. Because these differences are so great, it is possible to argue that the hyponatremia was merely a result of water intoxication a n d h a d nothing to do with oxytocin infusion or, indeed, pregnancy. This is unlikely because oxytocin begins to exert its antidiuretic effect at very small doses (2-5 m U / m i n ) , and there is an individual sensitivity to the antidiuretic effect of oxytocin (1). Whether the fall in serum sodium is greater than can be accounted for by the retention of water alone (7) is difficult to say as the original serum sodium is not known in any of these cases.
and oxytocin dosage in three subjects with Rate of Oxytocin Infusion (mU/min)
Dosage of Oxytocin (IU)
Serum Sodium (mmole/liter)
2-10 2-4 2-10
1~5 10 12
ÏÏ4 121 112
InlJ Gynaecol Obstei 17
252
McKenna and Shaw
Whether the stress of spontaneous labor with small doses of exogenous oxytocin and pethidine (5) combined to produce an antidiuretic response with a resultant greater decrease in the serum sodium than could be expected from dilution alone is largely irrelevant to the point of reporting these three cases. T h e point of these cases is that they each were initially quite healthy a n d then were given a lifeendangering problem of iatrogenic origin. T h e fault was m a d e all the worse by the IV administration of 5% dextrose in water in volumes far in excess of requirements. T h e diagnosis of hyponatremia is based on an awareness that a fit might be due to this problem. Clinically, the patient is usually normotensive with no proteinuria and has some edema. Although not easy to spot in a laboring patient, alteration in levels of consciousness was retrospectively noted in two of our three patients. Electrolyte measurements then confirmed the diagnosis of hyponatremia. T h e subsequent treatment that these patients received included: (a) stopping the fits a n d ensuring the availability of basic life-support measures; (b) stopping the insult, ie, stopping dextrose in water and oxytocin; and (c) resisting the temptation to give a diuretic (instead slowly giving normal saline and considering giving hypertonic saline) (2). Prevention of hyponatremia entails the possible revision a n d adequate supervision of existing fluid administration regimens in delivery suites. As a rule, no more than 2 liters of 5% dextrose in water, the traditional intravenous fluid given to women in labor, should be given in any one labor and certainly no more bottles should be erected without medical reassessment of the patient. Since a retrospective review of labor charts shows that other patients have also received similar quantities of intravenous fluids in normal or prolonged
IntJ Gynaecol Obstet 17
labors, the occurrence of fits in these three cases could suggest a susceptibility to oxytocin.
REFERENCES 1. Abdull-Karim R, Assali N S : Effects of oxytocin on renal haemodynamics a n d water a n d electrolyte excretion. J L a b Clin Med 57:522, 1961. 2. A h m a d AJ, Clark E M , Jacobs M S : W a t e r intoxication associated with oxytocin infusion. Postgrad M e d J 5/:249, 1975. 3. Burt R L , Oliver K L , W h i t n e r DL: W a t e r intoxication complicating elective induction of labour at term. Obstet Gynecol 3*212, 1969. 4. Lauersen U H , Birnbaum SJ: W a t e r intoxication associated with oxytocin administration during saline induced abortion. Am J Obstet Gynecol 121:2, 1975. 5. Liggins G C : Antidiuretic effect of oxytocin, morphine a n d pethidine in pregnancy and labour. Aust N Z J Obstet Gynaecol 3:81, 1963. 6. Liggins G C : T r e a t m e n t of missed abortion by high dosage Syntocinon intravenous infusion. J Obstet Gynaecol Br C o m m o n w 69:211, 1962. 7. M o r g a n DB, Kirwan NA, Hancock K W , Robinson D, A h m a d S: W a t e r intoxication and oxytocin infusion. Br J Obstet Gynaecol 84:6, 1977. 8. S h i p m a n K H , Sitprija V, Holmes S H : Syntocinon in the diagnosis of acute oliguria. Obstet Gynecol 2.3:242, 1969. 9. Storch H S : Acute water retention associated with continuous slow infusion of oxytocin. Obstet Gynecol 37:109, 1971. 10. Whalley PJ, Pritchard J : Oxytocin and water intoxication. J A M A 756:601, 1963.
Address for reprints: Ft. W. Shaw Dept of Obstetrics and Gynaecology Birmingham Maternity Hospital Edgbaston, Birmingham, B15 2TG England
