Friday, October 22 -Day +9

Wednesday Collin seemed to be doing a little better. He was afebrile all day, which was a welcome change. His diarrhea slowed down. He received another blood transfusion and another platelet transfusion. He rested a lot, but did have one or two times when he sat up for a bit and was interested in playing. When I weighed him in the morning, his weight had increased by .6 k in 24 hours, which is 1.32 lbs. He was also puffy looking. This meant his fluid output was lower than what he was taking in, so he was given a dose of Lasix, a diuretic, to help him pee more to get rid of some fluid. He also was switched to a different anti-fungal drug instead of the one that had caused rigors and possibly some of the increased temperatures (referred to as "shaking and baking") the day before. 

Wednesday night before I went to sleep, I thought Collin felt warm when I changed his diaper. Sure enough, he had a low grade fever and was given Tylenol. Around 4:30 Thursday morning, he woke up crying. I checked his diaper but it wasn't wet. I was trying to comfort him, and his nurse came in. She asked about his diaper, and I told her it was dry, and I figured someone had changed him. She said she had changed him a while before then, but that diaper hadn't been wet either. She had let the covering resident know, and the resident had contacted the covering physician, but he didn't feel it was necessary to order another dose of diuretic at that time. So at 4:30 am, Collin still had not peed much, he was so puffy that his belly was hard and his bellybutton was sticking out, and he was having some difficulty breathing. We weighed Collin, and his weight had increased another .9 k, which is almost 2 lbs. His oxygen level was also decreased, and he seemed to be having slight difficulty breathing. The attending physician was notified, and he finally ordered a dose of Lasix, and X-Rays of Collin's chest and belly.  

Later in the morning, when the attending physician came by, he said the X-Ray showed haziness in Collin's right lung, which could have been either from fluid or infection. He ordered more Lasix to try to help Collin's system get rid of some of the fluid it was retaining. Another chest x-ray would be done Friday morning to see if the right lung had improved after some of the fluid was reduced. The doctor also ordered a doppler ultrasound study to be done on Collin's liver.  Finally, he added a steroid and a nebulizer treatment to reduce the upper airway inflammation that was evident when Collin was breathing. He felt this was because Collin's white blood cell count had jumped overnight, so there were white blood cells, whose job it is to fight infection, attacking the mucositis in Collin's body, which can cause inflammation.

The nebulizer treatment and the steroid seemed to help Collin's stridor. He was put on oxygen and we switched the humidifier that we had rigged over his bed to oxygen from regular air to try to prevent his from getting too dried out. He was doing well and maintaining his oxygen saturation level throughout the day. The liver ultrasound showed that Collin's blood was going into his liver, but instead of going out of the liver after being filtered, it was backing up and seeping out the way it came in. At that point he had all but one symptom of VOD, or veno-occlusive disease, a complication from the high dose chemo and stem cell transplant.

From Wikipedia:
"Hepatic veno-occlusive disease or veno-occlusive disease (VOD) is a condition in which some of the small veins in the liver are blocked. It is a complication of high-dose chemotherapy given before a bone marrow transplant (BMT) and is marked by weight gain due to fluid retention, increased liver size, and raised levels of bilirubin in the blood. The name sinusoidal obstruction syndrome is now preferred if VOD happens as a result of chemotherapy or bone marrow transplantation.  In the BMT setting, VOD is felt to be due to injury to the hepatic venous endothelium from the conditioning regimen."

Basically, the high dose chemo injured the vein walls, which allows fluid to leak out of the veins into open spaces, called third spaces, in the body. It was likened to a hose that has holes in it; when water goes through the hose, it comes out of the little holes instead of going all the way through the hose like it's supposed to. This fluid is leaking into Collin's abdominal cavity, which is putting pressure on his lungs, making it difficult to breathe. The blood vessels that carry blood through the liver become swollen and blocked. Without a supply of blood, the liver cannot remove toxins, drugs, and other waste products from the bloodstream. Pressure and fluids build up in the liver, causing swelling and tenderness in the liver area. The kidneys may retain excess water, causing fluid to build up in the body and swelling in the legs, arms, and abdomen. In severe cases of VOD, excess fluid in the abdominal cavity puts pressure on the lungs making it difficult to breathe. Symptoms of VOD include rapid weight gain, swelling, jaundice, an enlarged liver, pain or tenderness in the area of the liver, and accumulation of fluid in the abdominal cavity (called ascites).

There is no actual cure for VOD. The medical team tries to prevent more serious complications, which can include kidney, heart and lung failure, and even death. Collin has all of the symptoms but the jaundice. His bilirubin level is slowly climbing, but is still within normal limits. There is a drug called Defibrotide which can successfully treat the VOD over time. While the drug has been used in Europe for twenty some years, it has not been approved by the FDA for use in the US. The drug company that makes it is performing clinical trials, and Collin meets all the criteria for the trial but one: his bilirubin level isn't high enough yet. So at this point the only thing we can do is manage the symptoms he has now; oxygen to help him breathe, diuretics to help get rid of some of the fluid, pain meds to keep him as comfortable as possible, and possibly having to tap his abdomen to drain some of the fluid out. The problem with tapping his belly is the risk of infection or bleeding; his immune system is still very weak, and he requires regular platelet transfusions to help his blood clotting abilities so he doesn't bleed to death. Once his bilirubin reaches a certain level, he would qualify for the study and could start the drug. The medical team is going to call the study coordinator and ask if an exception can be made, but I've been told not to get my hopes up that they will allow Collin to have the drug before his bilirubin reaches the required level. I'm praying for compasison, because it seems ridiculous to wait until he gets worse when we know he's headed that way anyway.

So last night, Collin was maintaining his oxygen saturation level on oxygen one minute, and then that changed in an instant. Despite oxygen his sats were dropping, and nothing we did was increasing them. Collin's nurse called for a rapid response, and within a minute or two there were twenty different people in his room assessing Collin. He was rushed back to the pediatric intensive care unit where they are better equipped to handle such an emergency.

The team finally got him stabilized, and another chest X-Ray was done. This showed marked improvement in the haziness that was seen yesterday. This morning when the transplant doctor stopped in, he said they are trying to get the drug, but until they can, either out of compassion or because Collin's bilirubin goes high enough, they will do everything they can to maintain Collin's condition and prevent him from getting worse. At this point there is little hope the condition will turn around on it's own. So far, there has not been permanent damage done to Collin's liver. At tnis point, the condition isn't likely to be fatal, but the doctor said he won't sugar-coat things and that it could head that way, but he will let us know if things are headed that way. The transplant doctor, Collin's oncologist, and his hem/onc nurses have seen kids in worse condition than Collin is in survive, so I am trying not to lose hope.

After rounds this morning, the plan is to keep Collin in the PICU another night. There are many calls into the people in control of the Defibrotide; it seems they are preparing to ship the drug from Dallas so that it is here when it's needed, whether they allow him to have it early or his bilirubin level gets high enough. At the rate the level has increased so far, it probably won't be long until it's high enough to qualify for the trial anyway. I will do my best to post updates as I have them.