Case hinges on use of off-label tocolytics

Andrew I. Kaplan, Esq, is a partner at Aaronson, Rappaport, Feinstein & Deutsch, LLP in New York City, specializing in medical malpractice defense and healthcare litigation. He welcomes feedback on this column via email to aikaplan@arfdlaw.com.

Facts

A woman carrying monochorionic-diamniotic twins in 2008 began seeing perinatologists Drs. A, B, and C on referral from her ob/gyn, Dr. D. She had had one previous live cesarean delivery. 

On June 5th, cervical shortening was noted by Dr. C. On June 9th, when the patient had reached 23 weeks’ gestation, Dr. B recommended that the patient be admitted to the defendant hospital for cerclage, which was performed by Dr. D. The patient was then placed on indocin for 48 hours by Dr. D but began having premature contractions thereafter, for which she was begun on terbutaline at the recommendation of Dr. A on June 14th.

On June 16th, the patient had some moderate contractions documented by the nursing staff, consisting of 4 contractions anywhere from 2 to 22 minutes apart, lasting 60 seconds. As a result of discussions between
Drs. D and A, the patient was discharged on terbutaline via pump with home care from Group E. Dr. D signed the order for the home infusion and was to receive reports from Group E.

The patient was on home therapy for a month and had daily monitoring, although there was no clear-cut and documented daily monitoring of her heart rate. On June 21st, the patient was spiking a pulse of 117, and on June 24th it reached 122. The Group E notes show that a nurse suspended the automatic bolus and asked the patient to retake her pulse, which was recorded 3 hours later as 103. On the 25th, the patient spiked another pulse of 114; it went up to 115 the next day, and on the 27th, it went up to 120.

A 1:16 pm note on June 27th by Group E indicates that the patient’s pulse went up to 130 on that date, and that at 3:25 pm, with a pulse of 127, the patient was complaining of shortness of breath and “feeling a little strange,” so the pump was stopped and Dr. D’s office was alerted. The terbutaline dosage was decreased, as was the frequency, and a 4:46 pm note indicates that the patient’s pulse went up to 133, but the pump was re-commenced by 5:54 pm. The pulses thereafter ranged from 103 to 115.

On June 26th, the patient was seen by Dr. C, who noted she was stable other than having a pulse of 124, although she had just received her bolus of terbutaline and the rate came down thereafter. On July 10th, Dr. B documented a positive fetal fibronectin (FFN) test performed by Dr. D on July 8th. The patient’s pulse was stable at 96 at that time. Dr. B saw the patient for a final visit on July 17, 2008, when she presented with a pulse of 100. Dr. B placed her on glyburide for gestational diabetes.

On July 19th, the patient’s husband found her unresponsive and in cardiac arrest. An ambulance was called and the patient was resuscitated and taken to a nonparty medical center. Her pupils were noted to be fixed and dilated but she had a blood pressure. She was placed on life support and had an emergency cesarean delivery. One infant was delivered stillborn and the second was born alive. That infant lived for 1 month but eventually died as a result of injuries including Grades III and IV intraventricular hemorrhages.

The mother was declared brain dead on July 24th. No autopsy was performed on the infant, but an autopsy on the mother revealed small atherosclerotic vessel disease. The coronary arteries appeared essentially unremarkable. The cause of death was listed as “anoxic ischemic encephalopathy post cardiac arrest secondary to small vessel arteriosclerotic heart disease.”

Allegations

The plaintiffs alleged that the defendants were negligent in prescribing a terbutaline pump for outpatient therapy, because that use was off-label and both the FDA and ACOG at that time proscribed utilization of tocolytics and, particularly terbutaline, for longer than 72 hours. The plaintiff asserted that the science showed that the utilization of terbutaline for off-label purposes came with an increased risk of severe tachycardia and cardiac arrhythmia and that defendants D and A, in prescribing a terbutaline pump to be utilized on an outpatient, were negligent in failing to evaluate the patient’s cardiac status by EKG, electrolytes, or consultation with a cardiologist prior to hospital discharge.

Furthermore, the plaintiff asserted that the patient was not properly monitored despite bouts of significant tachycardia at home after discharge from the defendant hospital and also that in the absence of any contractility in the weeks after the commencement of terbutaline, it would have been appropriate for a trial off the terbutaline to see if the patient’s preterm labor would recur, and that Drs. B and C were in the best position to take the patient off the terbutaline when they saw her in the office after discharge from the defendant hospital.

The plaintiff contended that the patient should have been given a trial off the terbutaline as an outpatient, and that the failure to do so resulted in cardiac arrhythmia and sudden cardiac death.

Discovery

Dr. C stated that the terbutaline in and of itself was not the cause of this patient’s death. Rather, he felt that Group E, the non-party home healthcare agency that was monitoring the patient’s terbutaline administration via pump at home, was responsible for failing to appropriately give “hypotensive precautions” to the patient, and their failure to do so resulted in a vasovagal response, wherein the patient fell or fainted in the shower and hit her head. Thus, a subdural hematoma in conjunction with the twin fetuses compressing her aorta resulted in diminished blood flow to the brain and heart, putting the patient into cardiac arrest and brain death.

The private ob, codefendant Dr. D, proposed the same theory at his deposition, but the medical examiner called it a death secondary to cardiac arrest.

Dr. C was also of the opinion that when he saw the patient on June 26th after her discharge and she had a pulse of 124 within an hour of receiving a bolus of terbutaline, it came down during the course of her presentation, and thus he felt there was no need to alter her dosage or discontinue the drug. It was the position of all the physicians that in this particular patient, with a prior cesarean scar, twin gestation, cerclage, and positive FFN test, it would have been improper to discontinue terbutaline because she likely would have gone into immediate preterm labor.

The risk of uterine rupture given the prior cesarean scar was very real, and the doctors felt that the potential benefit of prolonging the pregnancy mitigated the risks, as long as the patient was being appropriately monitored. As to the theory that there was no pre-terbutaline EKG, Dr. C argued that the anesthesiologist performed one before the cerclage surgery, but he had to concede this was not a standard 12-lead EKG, and it could not rule out ventricular tachycardia.

The defendant perinatologists (Drs. A, B, and C) took the position that home care Group E was reporting directly to private ob codefendant Dr. D, which was the case, but the plaintiff argued that as the perinatologists, they still had an obligation to avail themselves of that information.

The expert evaluation was mixed. One local perinatologist was opposed to long-term maintenance on tocolysis. He believed that the proper methodology was to put the patient on bed rest, to monitor her, and to let nature run its course. He did not believe that cerclage was warranted in a twin gestation in that there was no evidence that it would truly prolong the pregnancy. He felt this patient should have had a cardiology consult before she was put on long-term terbutaline and, at minimum, should have had an EKG and electrolytes performed.

A second perinatologist, however, felt the care was appropriate, warranted under the circumstances, and could not be said to any reasonable degree of medical certainty to have caused or contributed to the patient’s demise.

A pathology expert reviewed the autopsy slides and stated his opinion that the diagnosis of “small vessel arteriosclerotic heart disease” was inaccurate. He saw no evidence of small vessel disease. However, he could not rule out acute arrhythmia as a possible cause of death.

Analysis

This was a difficult case to settle. From a medical perspective, the care and treatment appeared to be appropriate, and the patient’s cause of death was speculative. However, from a litigation perspective, the perinatologists were fighting an uphill battle.

Despite the fact that terbutaline was used by many obstetricians and perinatologists in just this manner-to prevent premature delivery secondary to cervical incompetence-the fact of the matter was that it was “off label.” Both the FDA and ACOG warned against the use of tocolytics beyond 48 to 72 hours, but particularly terbutaline, in light of its propensity to cause tachycardia, pulmonary edema, hypoglycemia, shortness of breath, and chest pain.

While there is significant literature to support the proposition that the administration of terbutaline via pump is appropriate if the patient is adequately monitored, there were questions regarding the monitoring in this case and whether the patient was appropriately evaluated from a cardiac perspective before being placed on long-term tocolytics.

There was also the question of whether, once the patient’s contractility diminished or ceased, the tocolytics should have been discontinued, particularly given her spikes of tachycardia.

Ultimately, because the case portended significant sympathy for the loss of a mother and wife and her twin babies, and because communicating the treatment decisions to a lay jury would have been difficult, it was settled before trial.

The verdict

The 3 defendant perinatologists resolved the case before trial, with Dr. A and Dr. B paying 90% of the settlement and Dr. C paying 10%, for a total of $1.5 million. Co-defendant Dr. D ultimately obtained discontinuance.