Extra Topic 2.8 -- Fetal Bradycardia with Neuraxial Anesthesia & Denervated Heart

Question 1

You are looking at her ECG and note two different P-wave morphologies.

What do you think is going on?

(A 38-year-old, 64 kg female in labor is admitted for induction of labor. She is planning to receive an epidural at some point for pain control. You learn that she suffered from viral cardiomyopathy and required a heart transplant 8 years ago. Vital Signs: HR = 110; BP = 155/88 mmHg.)

Answer 1

The ECG of patients with a transplanted heart often shows two sets of P-waves,

with the origin of one P-wave being the native sinoatrial node,

while the origin of the other is the donor’s sinoatrial node.

While the native sinoatrial node may continue to be affected by autonomic influences, it does not alter cardiac function because the generated impulse is unable to traverse the suture line between the native heart and transplanted heart.

Question 2

A few hours later, the patient’s cervical dilation is progressing rapidly and your partner utilizes a combined spinal epidural technique (CSE) to control her labor pain.

Following placement, the patient experiences a tetanic uterine contraction and the baby’s heart tones go down.

Why might this happen?

(A 38-year-old, 64 kg female in labor is admitted for induction of labor. She is planning to receive an epidural at some point for pain control. You learn that she suffered from viral cardiomyopathy and required a heart transplant 8 years ago. Vital Signs: HR = 110; BP = 155/88 mmHg.)

Answer 2

Fetal bradycardia following the initiation of spinal analgesia may result when –

the rapid onset of analgesia leads to an abrupt decrease in circulating epinephrine, with subsequent uterine hypertonus (tachysystole) and decreased uterine perfusion

(spinal anesthesia → rapid decrease in pain → abrupt decrease in plasma epinephrine → decreased stimulation of B2-adrenergic receptors in the uterus → increased uterine tone → reduced uterine blood flow (most uterine blood flow occurs during uterine relaxation/diastole) → diminished fetal oxygen delivery → fetal bradycardia).

This effect on uterine tone associated with the initiation of neuraxial anesthesia to control labor pain is more pronounced when:

1. oxytocin is utilized,
2. spinal anesthesia is employed rather than epidural (more rapid sympathectomy),
3. the height of sensory blockade is relatively higher, and
4. when there is a greater difference between pre- and post-analgesia pain scores.

Other potential causative or contributing factors would include:

1. the presence of a nuchal cord;
2. maternal hypotension secondary to –
   
   • sympathectomy (spinal anesthesia),
   • aortocaval compression (inadequate left uterine displacement),
   • hypovolemia (the patient’s high blood pressure may be a pain response, but could also be the result of chronic hypertension and/or preeclampsia), or
   • suppression of the hypothalamic-pituitary-adrenal axis (heart transplant patients often receive exogenous steroids, making it necessary to provide steroid supplementation during labor and delivery);
3. impaired uteroplacental perfusion (this patient with high blood pressure may be suffering from preeclampsia which is associated with impaired uteroplacental perfusion); and
4. significant maternal respiratory depression (secondary to intrathecal narcotics).

Fortunately, fetal bradycardia following neuraxial anesthesia is usually transient and readily treatable.

Moreover, it does not increase the incidence of emergency cesarean section or the overall risk for adverse outcome.

Question 3

What would you do?

A few hours later, the patient’s cervical dilation is progressing rapidly and your partner utilizes a combined spinal epidural technique (CSE) to control her labor pain.

Following placement, the patient experiences a tetanic uterine contraction and the baby’s heart tones go down.

(A 38-year-old, 64 kg female in labor is admitted for induction of labor. She is planning to receive an epidural at some point for pain control. You learn that she suffered from viral cardiomyopathy and required a heart transplant 8 years ago. Vital Signs: HR = 110; BP = 155/88 mmHg.)

Answer 3

In addressing the fetal bradycardia, I would:

1. provide supplemental oxygen,
2. ensure adequate left uterine displacement
   
   • (especially important in this patient with a transplanted heart, due to the dependence on preload in responding to hypotension),
3. discontinue any intravenous oxytocin administration,
4. treat any maternal hypotension, and
5. consider fetal scalp stimulation.
6. If the uterine hypertonus and fetal bradycardia persisted, I would – administer a tocolytic (i.e. 50-100 mcg of intravenous nitroglycerine or 125-250 mcg of intravenous terbutaline).

Question 4

The baby’s heart tones improve and the decision is made to proceed for cesarean section due to severe preeclampsia.

How would you evaluate the patient preoperatively?

(A 38-year-old, 64 kg female in labor is admitted for induction of labor. She is planning to receive an epidural at some point for pain control. You learn that she suffered from viral cardiomyopathy and required a heart transplant 8 years ago. Vital Signs: HR = 110; BP = 155/88 mmHg.)

Answer 4

In evaluating this patient, I would:

1. talk to the transplant team about the patient’s cardiac status, immunosuppression, and the need for antibiotic prophylaxis ;
2. review the most recent echocardiography, endomyocardial biopsy, and/or coronary angiography results, and evaluate the patient for signs of rejection such as – arrhythmias, fever, malaise, shortness of breath, accelerated coronary atherosclerosis, and myocardial dysfunction (when there are signs of rejection, echocardiography, coronary angiography, and endomyocardial biopsy should be repeated as time permits);
3. identify and evaluate any pacemaker placed to control bradydysrhythmias (many post-cardiac transplant patients require a pacemaker for this purpose);
4. determine whether her hypertension is due to preeclampsia or is chronic in nature, and treat accordingly (cyclosporine-induced hypertension is common in this patient population);
5. evaluate her ECG for signs of myocardial infarction and/or ischemia, recognizing that cardiac denervation masks the usual symptoms associated with these events (i.e. silent ischemia);
6. identify any complications associated with immunosuppressive therapy, such as nephrotoxicity (secondary to cyclosporine therapy), bone marrow suppression, osteoporosis, hepatotoxicity, and opportunistic infection;
7. administer a stress dose of corticosteroid, if not already done (these patients are usually receiving steroids as part of their immunosuppressive therapy);
8. ensure normovolemia, recognizing that this preload dependent patient (transplanted heart) is likely hypovolemic (secondary to preeclampsia and possible chronic hypertension);
9. obtain a recent platelet level and identify any signs of coagulopathy, such as bleeding at IV sites or easy bruising (preeclampsia is associated with thrombocytopenia); and
10. carefully evaluate her airway, recognizing that pregnancy and preeclampsia increase the risk of difficult airway management.

Clinical Notes:

• 97% of patients develop hypertension by 10 years post-transplant.
  
  • This is often attributed to treatment with cyclosporine.
  • Treatment usually involves the use of a calcium channel blocker (i.e. diltiazem) and/or an ACE inhibitor.
  • Nifedipine may be a less desirable choice since it may cause significant vasodilation, which is poorly tolerated by these patients who are preload dependent.
  • B-blockers should also be avoided, if possible, since cardiac responsiveness during exercise is dependent on circulating catecholamines.
• Allograft rejection usually occurs in the first 6 months and presents with fever, malaise, arrhythmias, shortness of breath, accelerated coronary atherosclerosis, and myocardial dysfunction. Hemodynamic compromise is considered a late sign of rejection. Rejection is typically treated with steroids, but may require immunosuppression with IV immunoglobulin or plasmapheresis.
• Immunosuppressive therapy usually includes –
  
  • cyclosporine,
  • azathioprine, and
  • prednisone.
• Pregnancy is usually well tolerated by post-cardiac transplant patients.
• In the setting of renal dysfunction, AVOID drugs that may exacerbate renal dysfunction (i.e. NSAIDs) or primarily undergo renal excretion.

Question 5

Would you utilize her epidural catheter to provide anesthesia for the cesarean section?

(A 38-year-old, 64 kg female in labor is admitted for induction of labor. She is planning to receive an epidural at some point for pain control. You learn that she suffered from viral cardiomyopathy and required a heart transplant 8 years ago. Vital Signs: HR = 110; BP = 155/88 mmHg.)

Answer 5

Assuming there were no signs of coagulopathy (increased risk in the setting of preeclampsia),

I would utilize her epidural catheter for the case in order to avoid instrumenting the airway of this pregnant and preeclamptic patient who is at increased risk for difficult airway management.

However, I recognize that immunosuppression therapy increases the risk for infection, and denervation makes the transplanted heart dependent on circulating catecholamines and preload

(autonomic influences are absent, but the Starling relationship between diastolic end-diastolic volume and cardiac output is normal).

Therefore, I would pay special attention to aseptic technique and raise the levels of epidural analgesia very slowly to avoid a rapid sympathectomy that would potentially reduce preload

(the preload dependence associated with the transplanted heart makes epidural anesthesia preferable to spinal anesthesia).

Clinical Notes:

• The Frank-Starling mechanism describes an increase in stroke volume that results from more forceful cardiac contraction in response to increased cardiac filling and ventricular wall stretching.
• There is no difference in outcome when comparing general to neuraxial anesthesia in these patients.
• General, epidural, and spinal anesthesia have all been successfully employed.
• Due to the increased risk of infection:
  
  • Invasive monitoring and lines should only be employed when necessary
  • Oropharyngeal intubation is preferred to the nasopharyngeal route (the latter is associated with an increased risk of infection due to the organisms typically located in the nasopharynx.)

Question 6

You decide to proceed with general anesthesia.

Just after induction the patient experiences a significant drop in blood pressure.

What do you think is going on?

(A 38-year-old, 64 kg female in labor is admitted for induction of labor. She is planning to receive an epidural at some point for pain control. You learn that she suffered from viral cardiomyopathy and required a heart transplant 8 years ago. Vital Signs: HR = 110; BP = 155/88 mmHg.)

Answer 6

Given the timing of her hypotension, the most likely etiology is

1. an anesthetic-induced drop in systemic vascular resistance, with a subsequent reduction in preload.
   
   • Since the transplanted heart is initially unable to respond to acute hypotension with an increase in heart rate due to the lack of autonomic innervation, it relies on adequate preload to maintain cardiac output
   • (since alpha- and B-receptors remain intact on the transplanted heart, there is a delayed increase in heart rate in response to increased circulating catecholamines).

I would also consider other potential causes or contributing factors, such as:

1. inadequate left uterine displacement
   
   • (leading to reduced preload);
2. arrhythmia
   
   • (cardiac arrhythmias may occur secondary to the lack of vagal innervation and/or increased levels of circulating catecholamines);
3. myocardial ischemia and/or infarction
   
   • (these patients often suffer from accelerated coronary atherosclerosis);
4. pulmonary thromboembolism
   
   • (the hypercoagulability associated with pregnancy increases the risk for developing deep venous thrombosis);
5. amniotic fluid embolism;
6. anaphylaxis (possibly secondary to antibiotic administration), or
7. adrenal suppression (most cardiac transplant patient are receiving exogenous steroids).

Clinical Notes:

• The response to circulating catecholamines is normal and possibly enhanced due to denervation sensitivity (increased receptor density), even though sympathetic innervation is absent.
• The heart rate response to normal respiratory variations (sinus arrhythmia), carotid sinus massage, valsalva maneuvers, and the oculocardiac reflex are absent.
• The absence of vagal influences causes a relatively high resting heart rate (90-120 beats/minute)

Question 7

How would you treat her hypotension?

(A 38-year-old, 64 kg female in labor is admitted for induction of labor. She is planning to receive an epidural at some point for pain control. You learn that she suffered from viral cardiomyopathy and required a heart transplant 8 years ago. Vital Signs: HR = 110; BP = 155/88 mmHg.)

Answer 7

In treating her hypotension, I would:

1. ensure adequate left uterine displacement;
2. evaluate her ECG for signs of arrhythmia and/or myocardial ischemia;
3. administer fluids to maintain high-normal preload, keeping in mind that overaggressive fluid may lead to pulmonary or cerebral edema in this patient with severe preeclampsia;
4. administer a direct vasoconstrictor, such as phenylephrine (indirect vasopressors, such as ephedrine, are not as effective due to the absence of catecholamine stores in myocardial neurons); and
5. reduce or discontinue any volatile agent.
6. If these interventions are ineffective, I would – consider starting an isoproterenol or epinephrine infusion and
7. evaluate the patient for signs of anaphylaxis (i.e. hives, flushing, swelling, and bronchospasm) or pulmonary embolism (thrombotic or amniotic fluid).

Clinical Notes:

• The denervated heart:
  
  • Exhibits minimal response to – pancuronium, digoxin, nifedipine, anticholinergics (atropine, glycopyrrolate, and scopolamine), ephedrine, cholinesterase inhibitors (neostigmine, edrophonium, pyridostigmine, and physostigmine), or nitroprusside.
  • Is more responsive to – isoproterenol (used if increased chronotropy is required), phenylephrine, dobutamine, dopamine, and epinephrine.

Question 8

It becomes necessary to administer a nondepolarizing muscle relaxant during the procedure and you are preparing to reverse muscle relaxation at the end of the case.

Is it necessary to administer a muscarinic agonist along with the cholinesterase inhibitor in the setting of a denervated heart?

(A 38-year-old, 64 kg female in labor is admitted for induction of labor. She is planning to receive an epidural at some point for pain control. You learn that she suffered from viral cardiomyopathy and required a heart transplant 8 years ago. Vital Signs: HR = 110; BP = 155/88 mmHg.)

Answer 8

I would administer a muscarinic antagonist along with the cholinesterase inhibitor for reversal of muscle relaxation,

since some cardiac reinnervation may occur after 6 months post-transplant.

In managing muscle relaxation for this patient, I would also keep in mind that

azathioprine may competitively antagonize neuromuscular blocking drugs, and

cyclosporine may potentiate the neuromuscular blocking effects of atracurium and vecuronium.