Crisis Management Guidelines – Familial Dysautonomia

Guidelines provided by Professor Channa Maayan, Former Director, Israeli Familial Dysautonomia Center, Hadassah Hospital Mount Scopus, Israel.

Nausea and Vomiting

The lack of coordination in the digestive system of patients with Familial Dysautonomia ( FD) causes return of food from the stomach to the esophagus and from the esophagus to the mouth ( Gastro Esophageal Reflux- GER) causing vomiting and aspiration to the lungs. When the stomach is full with food there is a higher incidence of vomiting. Sometimes there is a problem of air swallowed during feeding which distends the stomach, especially because of lack of coordination during feeding and increase tonus of the pylorus (which is the sphincter connecting the stomach to the intestines).

Part of the stomach content that returns to the esophagus may be partially aspirated to the lungs. Sometimes cough and choking results and sometimes vomiting follows the cough, but this is not always the case. Sometimes aspiration to the lungs is silent. The vomiting can be accompanied by hematemesis (blood in the content of the vomiting) as this is a stress situation. The vomitus can be black-brown- coffee ground ( blood from stomach) or red from a tear or ulcer in the esophagus.

It is common for FD patients to experience morning nausea (the trigger of which is unknown – sputum accumulation? Arousal?) This can usually last few minutes – few hours). If this is recurrent and is causing problems, medications can be given through gastrostomy I hour before waking.

In older ages, starting at 3 and 4 years of age, there are dysautonomic attacks. These attacks present with nausea and vomiting, increase in blood pressure and heart rate, blotching (red patches on the body), drooling, nervous/irritated behavior, aggression and sweating. Sometimes there are recurrent gestures of rubbing the hands over the body (self mutilation) especially before the attack or at the beginning of it. The crisis can last a couple of minutes, hours or days. The attacks appear as reaction to stress situation. Stress situations include emotional stress (anxiety before exam, or excitement before birthday) or physiologic stress such as any disease like common causes include flu, pneumonia, urinary tract infection, pancreatitis, inflammation and sputum. Other causes are fatigue, GER, stomach distention with liquid or gas, gall bladder problems, constipation or before menstruation in girls. During dysautonomia attack there is a risk of dehydration, aspiration to the lungs and pneumonia.

Hospitalization is needed according to the clinical situation and the parents’ experience.

General treatment recommendation for vomiting

Feeding with the patient in vertical position. The patient should stay seated for an hour after the attack so the food has time to move from the stomach to the intestine.
Frequent and small portions of foods. Slow eating, drinking with straw.
When there is increased pyloric tonus (passage between the stomach to the intestines) there is a problem with stomach clearing and it useful to give medication which relaxes the pylorus (prepulsid, metoclopramide).
If the treatment isn’t working, an alternative reason for vomiting should be sought, such as food allergy.
Suction of pulmonary secretions to avoid cough and esophageal irritation. This is done with a special suction tube.
Also see pharmacologic treatment in section on respiratory system.
Consider surgical treatment

General treatment recommendations for invasive studies and acute vomiting attack

We would like to emphasize that the recommendations below are general. Each attack should be treated according to each individual patient and according to the clinical presentation and symptoms.

The causes for the attack should be sought and treated (as previously mentioned common causes include flu, pneumonia, urinary tract infection, pancreatitis, gastro esophageal reflux and excitement)
In the physical examination special attention should be given to blood pressure, central cyanosis, oxygen saturation, cold and blue extremities, signs of dehydration like tenting of skin, eyes, and reduction in body weight.

Workup

Blood: BUN, electrolytes, liver and pancreatic functions, CBC
Cultures: if there is fever, blood and urine cultures
Urine: electrolytes (Na), microscopic sediment, specific gravity
Radiology: Chest X ray
GI studies to diagnose gastro esophageal reflux, gastritis and esophagitis.

Dangers of Dysautonomic attacks

Aspiration into the lungs of gastric acids because of vomiting, especially in patients who have not had fundoplication and gastrostomy and less in patients who have had this operation.
Hypotension and shock due to lack of fluids.
Renal failure due to severe hypotension.
Syndrome of Inappropriate ADH Secretion and low Na in serum
Anxiolytics IV should be given slowly. For example, Valium should be administered during 5 minutes. If medications are given faster, there is a danger of apnea, slower administration will not be efficient enough.
Hematemesis (bloody vomiting) or melena.

Goals of treatment during attack

Sufficient rehydration
Ensure stomach is empty of liquid and air
Treat acidity of gastric acids in esophagus during attack
Stop nausea with medications and induce deep sleep for at least one day
Ensure adequate oxygenation, especially during deep sleep since during this time blood pressure and oxygenation are reduced.

Treatment of dysautonomic attack

General

Immediate administration of fluids – 20 cc/Kg Ringer lactate or Saline. Followed by maintenance of 1/3-1/2 Saline with glucose 5% 130 cc/Kg per day ( for the first 10 kg then 100c/kg day for the next 10 kg). If there is loss of Na in urine and reduction of Na in serum, Na should be added in fluids at a rate below 90/cc/kg/day. Na should be added gradually. K should be added to IV fluids after the patient has urinated.
Stomach should be emptied from liquids and air. In patients with gastrostomy, the opening of the bag should be opened for drainage. In other patients NG tube may be placed (if tolerated by patient).
The patient should lie with head raised at an angle of 30 degrees.
Stop all food and drink.
Eye drops should be given more often than usual because of dehydration and because of the oxygen treatment (even with nasal cannula there is some of the flow will reach the eyes.

Pharmacologic treatment to reduce stomach acidity

Zantac (ranitidine hydrochloride (HCl)), IV 2-4mg/kg/24h
Zantac in syrup form may be given PR with a small tube if the patient does not have an IV line.
Maalox Suspension (Aluminum Hydroxide/Magnesium Hydroxide ) 10-15 ccX3/day
Metoclopramide 0.1- 0.2 mg/kg/d through gastrostomy or PO

Anxiolytic pharmacologic treatment

Effective treatment includes administration of Valium or Midazolam, that is a short acting Valium.
It is best to wait for an hour until the patient receives sufficient hydration IV and then start anxiolytic therapy, because these drugs reduce the blood pressure. Initially it is best that the doctor would administer Valium at 0.1-0.2 mg/kg/dose, slowly, during 5 minutes and it is best to start with the lower dosage. This should be repeated every 2.5-3 hours, according to the patient’s condition. Oxygen should be given (via nasal canula) during IV Valium treatment because blood pressure reduction causes acute reduction of Oxygen saturation. Oxygen administration may prevent apnea.
IV Midazolam – preferably not to administer at the beginning of the attack (even though some children react well to it even at the beginning of the attack). It is usually more effective when the attack is slightly improving.
Continuous drip of IV Midazolam 0.5-3 mcg/kg/min.
The danger of IV administration is that if there is an error in drip adjustment a large amount of Midazolam may be administered suddenly and the patient may stop breathing while no nurse or doctor is around. Midazolam should not be given at home (not intra-nasally, bucally, orally or IV).
In order to avoid giving frequent amounts of Valium and in order to avoid drug tolerance (in which case the dose would have to be increased), it is best to alternately supplement this treatment with additional medication.

Other medications to treat acute attack

CAUTION! Two medications should never be administered concomitantly for fear of severe drop of blood pressure. In severe attacks anxiolytic treatment should be continued for 24 hours, following which a 1-2 hours break should be considered, and if the attack perseveres anxiolytic treatment should be resumed

Clonidine (Normopresan, Catapres) – reduces sympathetic activity. Before administration ensure blood pressure isn’t low. Dose: 0.05-0.1 mg/dose (through gastrostomy) alternately with Valium ( 0.1 mg/kg) every 2.5 -3 hours ( give Clonidine for 2.5 hours; then switch to Valium for 2.5 hours; then switch back to Clonidine for 2.5 hrs – etc). The timing depends on the patients, as some patients are more tolerant to the drugs and need more frequent administration. The drug should be given when the patents shows signs of waking up ( usually 2.5 hours)
Chloral Hydrate, Trichlonam – use of this medication had been reduced because of tolerance and addiction and side effects. Patients who have infrequent attacks may benefit from this medication. Dose: 50-75 mg/dose for children up to 10 years. After 10 years dosage should be adjusted, alternate with Valium.
CAUTION! Chlorpromazine (Largactil / Thorazine,) – Should not be administered for FD patients because severe side effects have been documented, associated with reduction of blood pressure.
Promethazine Hydrochloride (Phenergan) – rarely helps patients
Tigan (Trimethobengamide hydrochloride) – used by few patients only in the USA.
Brotizolam (Bondormin / Lendormin) – derivative of Valium. Don’t give sublingual

Other medications that have been tried and were not found useful are: Metoclopramide, Zofran (ondansetron hydrochloride) and various CNS medications such as Halidol, Lithium etc.

Before you give either Clonidine or Valim , check blood pressure and if low ( like 100/60mmHg) don’t give the drug and give fluids in a push until the blood pressure is elevated ( or give once florinF if you can’t elevate it ) and the give the drug ( Clonidine or Valium). Unless the patient sleeps deeply he will not get out of the crisis quickly. The medications should be continued in a strong crisis at least 12-24 hours. If the patient is better, stop the Valium and continue with lower dose Clonidine every 5 hours twice( it is not advised to stop Clonidine abruptly) and then stop.

Gutrone(midodrine hydrochloride) must be stopped if the patient was getting it as a routine before

Please, give oxygen by nasal canula in crisis even if the O2 saturation is normal, as the above medications can cause the blood pressure to drop. In FD there is coupling between oxygen content and blood pressure. Low blood pressure can cause further decreases of O2 content in blood and then further decrease of blood pressure even to respiratory and cardiac arrest.

Drugs mode of administration

As the patient has nausea it is advised not to give medications orally. Crushing the tablets and giving rectally is the best, however some patents disagree.

IV Valium has its risks ( as above), Clonidine IV is not always available.

If the patient has a gastrostomy, they can be given through it, however in crisis there is ileus and this will decrease the effectiveness.

When the crisis is over:

There is a “grey” zone in which the patient seems to be OK, however if one rushes with normal food and fluids the crisis can recur.

When the crisis is over start with soft and not acidic food and gradually increase the fluids with electrolytes through the gastrostomy.
The medications should be stopped gradually as above