What to Expect During Hospitalization for Hemolytic Uremic Syndrome

Children with HUS average about two weeks in the hospital, with a range of three days to three months. Approximately two-thirds require dialysis during the acute phase of the disease. Adults with HUS are typically in the hospital longer because their course of illness tends to be more severe.

There is no effective therapy for HUS—it cannot be stopped with medications or other therapies. Instead, treatment is supportive, which includes meticulous attention to fluid and electrolyte balance—the cornerstone of survival. The unnecessary use of antibiotics and antimotility agents is contraindicated in acute diarrhea illness and has been shown to increase the incidence of HUS.

In some cases, eculizumab (Soliris™, a humanized recombinant monoclonal antibody known to prevent complement activation) has been used to treat HUS, but it is unclear whether this is effective for diarrhea positive HUS (D+ HUS). Eculizumab has been proven effective in atypical or diarrhea-negative HUS (D- HUS). In the Germany epidemic, early studies suggested that eculizumab was effective in a number of children with severe HUS and severe neurologic complications. However, later studies concluded that eculizumab therapy was not beneficial as compared to standard therapy. Before implementation of any new therapy for HUS, it will be important for controlled trials to be performed to demonstrate efficacy. Future therapies might include monoclonal antibodies that neutralize the Shiga toxins; animal models of such antibodies have been shown to be effective in decreasing the severity of HUS when administered before and after onset of bloody diarrhea.

During the acute phase of HUS, the inflamed colon is usually non-functional for a week or two, and total parenteral nutrition (TPN) may become necessary. TPN is a complete form of nutrition, containing protein, sugar, fat, and all needed vitamins and minerals for individuals unable to absorb adequate nutrition through their intestines (enterally). TPN is administered through a peripherally-inserted central catheter (PICC) that allows for infusion of a highly-concentrated solution through a large vein. Even after intestinal function recovers, most patients continue to have a poor appetite for a week or longer. During this time, the PICC line can be discontinued and nutrients given enterally through a nasogastric (NG) tube.

Reduced or absent urine output (oligoanuria) occurs in most cases of HUS. While urinary output usually rebounds after a week, the duration of oligoanuria can be variable—as brief as two to three days, or up to a month or longer. Dialysis is required if a patient is not producing adequate urine, which cleanses the body of uremic toxins and maintains fluid and electrolyte balance.

Most young children with severe HUS require dialysis via the peritoneal cavity, called “peritoneal dialysis,” which has fewer negative side effects (such as nausea, vomiting, cramping, and weight gain) than hemodialysis and avoids traumatizing their much-smaller veins. However, if they exhibit significant and prolonged colitis, hemodialysis becomes necessary. Peritoneal dialysis requires placement of a catheter (tube) through the abdominal wall and into the peritoneal cavity.

Older children and adults are generally treated with hemodialysis, which circulates blood through a filtration machine to remove uremic toxins, normalizes blood chemistries, and corrects any circulatory fluid overload (often appearing as non-dependent edema or anasarca). Hemodialysis requires that venous access be established by inserting a temporary central catheter similar to a PICC line.

The majority of HUS victims require one or more blood transfusions to treat severe anemia; platelet transfusions are sometimes needed to diminish the risk of bleeding in those with severe thrombocytopenia (i.e. platelet counts less than 10,000) to control bleeding. More than half of HUS patients experience transient high blood pressure that is usually mild and labile, but which may be severe enough to require treatment with anti-hypertensive drugs.

Physicians caring for patients with acute HUS must remain vigilant for signs of involvement of organs other than the kidneys (“extra-renal”). Intestinal necrosis and perforation can occur at any time during this phase of the disease, which can be fatal if not promptly diagnosed and surgically treated. Pancreatic damage can cause insulin-dependent diabetes mellitus (IDDM), which is usually temporary but may require parenteral insulin. Permanent IDDM has been reported. Extra-renal complications occur not only in the acute setting but may also be seen well after recovery from the acute phase of HUS.

Heart and lung injury is rare in HUS, but can be fatal if it occurs. Brain damage (encephalopathy) can cause stroke or cerebral edema (swelling of the brain) and is the most frequent cause of death in HUS patients.

More frequently, encephalopathy results from acute metabolic imbalances (metabolic encephalopathy) and is caused by abnormal levels in the blood of sodium, glucose, calcium, or very high levels of metabolic waste products. Since metabolic abnormalities can result from acute kidney injury, they can be successfully treated by dialysis. Twenty-five years ago, the prevalence of metabolic encephalopathy was about 50%. More recently, with earlier diagnosis and more timely treatment, the prevalence has been brought down to about 25%.

Seizures are the most dramatic central nervous system (CNS) manifestation of HUS; they are more likely to occur in children. The incidence is greater in toddlers (30%) than in older children (15%). Unfortunately, structural damage to the brain—through stroke or swelling—has not decreased over time. If cerebral edema becomes severe, an increase in intracranial pressure can strangulate the brainstem, causing rapid death. Fortunately, most children recover normally from HUS and do not have long-term complications from CNS involvement. Studies have shown that children discharged without neurologic injury do not demonstrate an increased risk of subclinical problems with learning behavior or attention; however, some children with major neurologic symptoms have exhibited subtle neurologic sequelae, including clumsiness, poor fine motor coordination, hyperactivity, and distractibility.