Case 11 A child with leukaemia and tummy ache
Simon, a 4-year-old boy with Acute Lymphoblastic Leukaemia (ALL), has just completed his second delayed intensification in the current UK ALL trial at the regional Paediatric Oncology Centre (POC). His parents phone the children’s ward at the local DGH, their Paediatric Oncology Shared Care Unit (POSCU), to which they have open access. Simon is complaining of tummy ache and has had two episodes of loose stools containing a small amount of blood. His parents have taken his temperature and it is 38.7°C. The nurses have advised them to come in for review and on arrival his temperature is 37.4°C, pulse 140/min, BP 120/50 mmHg and respiratory rate 40/minute. He is seen within 10 minutes by Dr Joseph, the ST1 doctor, who learns that before Simon’s recent chemotherapy he had had intermittent abdominal pain and minor bleeding opening his bowels due to constipation, a common problem during treatment with vincristine. Regular lactulose is helping. His younger sister also had tummy ache and loose stools a few days ago and is now well. On examination, Simon is cheerful and cooperative and is well-perfused with warm hands and feet. His chest is clear, heart sounds are normal and his central line site appears clean. His abdomen is slightly distended but soft with possibly some right lower quadrant tenderness but no guarding and normal bowel sounds. The anus is slightly red with a small tear to which Dr Joseph ascribes the recent bleeding. His buccal mucosa is inflamed with some sloughing. Simon’s shared care record shows that on discharge from the POC two days previously the haemoglobin was 11.9 g/dL (normal 12–15 g/dL) and the WCC was 4.5 × 109/L (4.5–13 × 109/L) with neutrophils of 3.1 × 109/L (1.5–6 × 109). Dr Joseph consults the POC sepsis guidelines and decides that because the temperature is now below the threshold for treatment, and as Simon is unlikely to be neutropenic yet following his recent chemotherapy, he does not need immediate antibiotics. Dr Joseph makes a diagnosis of probable viral gastroenteritis but asks the nurses to send all his bloods including blood cultures and advises that she will review the results as soon as they are available. Simon is admitted for observation.
Do you agree with this management plan? Would you have done anything differently?
Thirty minutes later Dr Joseph is bleeped and told that the central line will not sample. She gives a verbal instruction to start a 4 hour urokinase infusion and to put some local anaesthetic cream on a few peripheral veins. Dr Joseph returns 2 hours later and is surprised but pleased to insert a cannula easily despite the multiple drips that Simon has had prior to his central line. He is extremely cooperative and has warm hands with easily visible veins.
What would be your assessment of this scenario?
One hour later the nurses call to say that Simon is very quiet and sleepy. His temperature is 38.8°C, pulse 190/min and they cannot measure his BP. They have commenced oxygen treatment because his saturations in air were 78%. On examination Simon is obtunded, has a central capillary refill time of 3 secs, warm peripheries and a respiratory rate of 60/min. A capillary lactate is 7.4 mmol/L (normal<2 mmol/L). The ST4 is called and makes a diagnosis of Gram negative shock, gives 2 boluses of 0.9% saline and calls the anaesthetist. Simon is intubated, ventilated and commenced on inotropes. He is transferred to the PICU at the POC but sadly dies 4 days later of multiorgan failure. His parents file a law suit based on the failure to recognize his illness on admission, the failure to follow available guidelines and the resulting delay in starting treatment culminating in his death. They quote the fact that ALL has an overall 5-year survival rate of 85%.
Expert opinion
Febrile neutropenia is a medical emergency in children receiving chemotherapy due to the risk of Gram negative sepsis in an immunocompromised host which has an estimated mortality of 40–50%. Once cancer is in remission, infection is the commonest cause of death. The risk is highest following intensive chemotherapy courses but can occur at any time during treatment. All POCs have guidelines for the management of fever in a child undergoing chemotherapy which include temperature thresholds for urgent treatment (often 1 temperature of 38.5°C or 2 temperatures of 38°C in a 4 hour period) plus the advice that any unwell child should receive immediate antibiotics (usually within 1 hour) irrespective of the temperature and the recent neutrophil count. Simon’s almost normal temperature on admission was irrelevant because the parents had already documented a fever that exceeded the threshold for treatment. Knowing this they may have already given paracetamol at home, a point that was not asked about by Dr Joseph. Neutrophil counts can drop very quickly especially with an intercurrent illness and treatment must not be delayed by waiting for results.
Simon’s temperature at home was sufficiently high to merit urgent broad spectrum iv antibiotics but he also had evidence of physiological compromise on admission. He was tachypneic, had a tachycardia that was not explicable by either fever or anaemia and had a wide pulse pressure. As in this case, children and young adults can maintain or even raise their systolic blood pressure until late in shock. Hypotension indicates critical illness and impending death. Simon has mouth and abdominal signs consistent with chemotherapy induced mucositis/typhilitis (neutropaenic caecal inflammation), as well as appendicitis putting him at high risk of the transmural passage of Gram negative organisms and the resulting characteristic shock. This risk should have been detected on admission and certainly when the cannula was inserted so easily. Cooperative 4 year olds with cannulas are very unusual. It is likely that prompt treatment would have saved Simon’s life.
Legal comment
It is probable that earlier treatment would have averted Simon’s death. That in itself would mean that compensation would be payable. The parents do not need to quote 5 year survival figures. It is enough to show that Simon would have survived this particular episode. Compensation, however, will be limited to a statutory sum of £11,800 for bereavement damages, the cost of Simon’s funeral and a sum for the pain and suffering that he endured in the days leading up to his death.
There appear to have been a number of mistakes in Simon’s treatment, as detailed in the Expert Opinion. Dr Joseph had read the POC guidelines, but had misinterpreted them. The parents had reported a high temperature at home and that should have been enough to trigger the administration of antibiotics. Perhaps the guidelines were not clear, in which case someone should try to improve them. That would be a systems failure.
Dr Joseph was on the right tracks. She at least looked at the guidelines. However, she should probably have recognized that this could be a complicated case and contacted someone with more experience to review the child.
