The uremic state impairs compensatory responses to ultrafiltration (UF). Intradialytic symptoms and hypotension can result and lead to premature discontinuation of treatment and sub-optimal dialysis. We report the benefits of mannitol, sequential dialysis and midodrine in reducing dialysis failures in those children prone to intradialytic hypotension. Prophylactic mannitol halved the odds of intradialytic symptoms and hypotension and increased UF volumes. Sequential dialysis halved the odds of symptoms but hypotension persisted. In one patient with refractory hypotension, only intradialytic midodrine consistently maintained acceptable intradialytic blood pressures, reduced intradialytic symptoms and increased the UF potential.