University College London Hospitals NHS Foundation Trust

6. Mrs E complains about aspects of care and treatment the Trust provided to her husband, Mr E. Specifically, she says the Trust:

• gave her husband an overdose of mannitol on 4 February 2022 • delayed reporting her husband’s scan results in December 2021. She had to chase up a follow up appointment and there was a lack of communication surrounding this.

7. Mrs E explained the overdose of mannitol led to her husband experiencing significant pain and distress which she feels could have been avoided. She said the pain following the mannitol overdose was not managed effectively. She also states that he developed acute kidney injury (AKI) because of this, and his health declined significantly.

8. She says the Trust avoided linking the overdose to AKI, and constantly blamed chemotherapy for the cause. Mrs E states Mr E had perfect kidney function until this point. As a result of the AKI, Mr E had to take opioid drugs and fentanyl, which Mrs E says caused him to suffer further.

9. Mrs E says if her husband had not been given the mannitol overdose, he could have been given chemotherapy and immunotherapy. She says he had responded well to chemotherapy previously and she feels he would have lived for longer and would not have suffered if treatment could have continued.

10. She says his opportunity to be treated was denied due to his AKI. She also stated her husband had consistently high blood pressure which led to a heart attack.

11. By bringing her complaint to us, Mrs E is looking for service improvements and financial remedy.

12. In January 2021, Mr E was diagnosed with transitional cell carcinoma of bladder (bladder cancer).

13. On 15 December 2021, the Trust conducted a CT scan (computed tomography scan, is a medical imaging technique that uses X-rays and computer processing to create detailed cross-sectional images of the body) on Mr E’s chest, abdomen, and pelvis.

14. On 7 January 2022, the Trust held an MDT (multi-disciplinary team) meeting to discuss Mr E’s care. The scan had not yet been formally reported. To prevent delay the MDT planned for his care without the formal radiology report being available.

15. On 12 January, the radiologist reported the MRI scan. The Trust stated the report was in accord with the MDT opinion, that there was evidence of progressive disease. The radiologist marked the report ‘red alert’ requiring urgent review. It explained that the wait for the scan report did not impact Mr E’s care because the MDT discussion had taken place as expected.

16. In January 2022, Mrs E says she had to chase for a follow up appointment following a scan in December 2021. This appointment did not take place until 12 January 2022, a month after the scan was reported. Reporting on the scan result showed metastasis (secondary cancer) at a very low level.

17. A clinical oncologist conducted a further scan at the end of January, which did not explain the swelling and reported that symptoms were latent to be related to the radiotherapy.

18. In February 2022, Mr E began first-line palliative chemotherapy for metastatic disease (refers to cancer that has spread from its original site to distant parts of the body).

19. On 4 February, the Trust administered 500ml instead of 100ml of mannitol (a drug used to treat kidney failure).

20. On 11 February, the oncologist assessed Mr E’s pain. The decision was made to admit him. The palliative care team reviewed his pain control and conducted investigation into the cause of the AKI during this admission.

21. On 21 February, the Trust discharged Mr E.

22. On 2 March Mr E attended the palliative care clinic due to the pain he was experiencing.

23. On 25 March, the Trust admitted Mr E with an acute kidney infection.

24. On 7 April, a palliative care consultant at the Trust raised concerns that Mr E was clinically deteriorating.

25. On 20 April 2022, Mr E sadly died.

Delayed scan results

30. Mr E had a CT scan on 15 December 2021. Mrs E states the Trust delayed reporting this and she had to chase this up. In its response, the Trust explained the scan was a treatment restaging scan, this was ordered as a routine scan, and an MDT discussion was scheduled for 7 January 2022 for the scan result.

31. At the MDT discussion the scan had not yet been reported by the radiologists, but the MDT team reviewed the images directly and agreed a plan for Mr E’s care and arranged an appointment.

32. The medical records show, after the MDT discussion on 7 January, Mr E’s appointment which was meant to be in March was brought forward to 12 January. The MRI scan was reported by the radiologist in the afternoon on 12 January.

33. Mrs E states this was an urgent scan, as it was marked as ‘red alert’. There is no clinical information included in the scan request and scan report to show this was an urgent scan. The scan was non-urgent.

34. Our oncology adviser explained the comment ‘requires urgent review – red alert’ is part of the scan report and has no bearing on the timing of issuing the report. This red flag alerts the referring clinician the scan report needs to be read urgently. The radiologist has included this sentence in the report to indicate that there was a new and significant finding on the scan that the radiologist wanted to highlight to the clinician who requested the scan.

35. The results once reported were urgent, which were discussed during an MDT meeting and action was taken as a result.

36. Our oncology adviser explained there were no reporting turnaround time guidelines in 2022. New NHSE guidelines came into effect in August 2023. These guidelines state the turnaround time for a non-urgent CT scan is 28 days.

37. Although this guidance postdates Mr E’s scan in December 2021, it is important that we consider this because his scan was reported within 28 days. Therefore, although this guidance would not have been place at the time, we cannot be critical of the Trust’s actions because the timeframe is in line with NHS England guidelines.

38. Our oncology adviser explained it may have been possible to discuss the scan in the urology multi-disciplinary team meeting around two to three weeks sooner, and commenced immunotherapy two to three weeks sooner, but it is highly unlikely that such a small difference in time would have led to any different outcomes in the long term. There would have been no significant change in the extent of tumour deposits in this time interval.

39. To conclude, there were no specific guidelines on radiology reporting at the time the events happened. It is our view that this reporting is consistent with current reporting guidelines for non-urgent scans.

40. We are therefore do not uphold this part of the complaint.

Mannitol overdose

41. Mrs E complains the Trust gave her husband an overdose of mannitol on 4 February 2022.

42. The medical records show on 4 February when Mr E attended chemotherapy, the Trust administered 500ml of mannitol (a drug used to prevent kidney failure) instead of 100ml. Mrs E is concerned this led to Mr E’s AKI. She states the Trust did not manage her husband’s pain effectively following the mannitol overdose.

43. In its response, the Trust explained it raised a clinical incident report following this and explained the initial impairment in renal function had several factors, probably caused by cisplatin (chemotherapy drug), chemotherapy, and possibly exacerbated by the high dose of mannitol.

44. Our oncology adviser explained from an oncology perspective, the Trust acted appropriately following the overdose, it followed duty of candour, completed a Datix report and informed the consultant.

45. Our adviser said they cannot say if the mannitol overdose contributed towards the AKI. The mannitol specification indicates that a dose of 500ml can be given if indicated. However renal toxicity (kidney damage) can occur and the risk of this is increased if nephrotoxic drugs (medication that can damage the kidneys) are given simultaneously.

46. We consider the Trust administering Mr E with 500ml of mannitol instead of 100ml to be a failing. We will explore the impact of this below.

Impact

47. We sought advice from our nephrology adviser to explore the impact of the failing we have identified.

48. Mrs E explained the overdose of mannitol led to her husband experiencing significant pain and distress which she feels could have been avoided, and this pain was not managed effectively. She says a result of the AKI, Mr E had to take opioid drugs and fentanyl, which Mrs E says caused him to suffer further.

49. She also states that Mr E developed AKI because of this, and his health declined significantly. She says the Trust avoided linking the overdose to the AKI, and constantly blamed chemotherapy for the cause.

50. Mrs E says if her husband had not been given the mannitol overdose, he could have been given chemotherapy and immunotherapy. She says he had responded well to chemotherapy previously and she feels he would have lived for longer and would not have suffered if treatment could have continued. She says his opportunity to be treated was denied due to his AKI.

51. She also stated her husband had consistently high blood pressure which led to a heart attack.

52. I have addressed each impact section below.

Kidney injury

53. On 4 February Mr E received the first of six planned cycles of chemotherapy comprising gemcitabine and cisplatin. His kidney function was well preserved based on a blood test checked shortly before treatment commenced and accordingly, the dose he received did not require reduction based on GFR (glomerular filtration rate, is a measure of how well the kidneys filter waste and excess fluid from your blood).

54. AKI is defined by a significant and brisk reduction in kidney function which is detected by either a reduction in urine output or more often, by a rise in serum creatinine (a blood marker used to assess kidney function) within a defined period.

55. Guidance from National Library of Medicine highlights cisplatin is associated with a relatively high incidence of AKI. Mr E had a history of heart disease and his echocardiogram showed a modest reduction in left ventricular function (the heart’s main pumping chamber), which could have marginally increased his predisposition to AKI but not to a substantial extent.

56. Our nephrology adviser explained Mr E did not fall into an obvious high-risk category, but AKI is nonetheless recognised as a potential complication of cisplatin even in those who are not at highest risk.

57. IV hydration is provided as a protection against AKI during the administration of cisplatin.

58. Co-administration of mannitol (an osmotic diuretic – drugs that increase urine output) with IV fluids is widely used as an additional measure to reduce the risk of cisplatin induced AKI.

59. Our nephrology adviser explained the dose of mannitol administered to Mr E by the Trust on 4 February was higher than the prescribed dose (100ml) but within the therapeutic range. The mannitol specification indicates that a dose of 500ml can be given if indicated.

60. Mr E developed stage 2 AKI between 4 and 11 February 2022. Stage two AKI is defined in NICE guidance on AKI, as a rise in serum creatinine of >200% and <300%, known or presumed to have occurred within the past seven days.

61. His creatinine (a waste product filtered out of the blood by the kidneys, making it an important marker for assessing kidney function) rose from 97 micromol/l to 235 micromol/l. Mr E was due to receive his second cycle of gemcitabine (chemotherapy) on 11 February. In view of his AKI, the Trust admitted him.

62. Mr E had several recognised risk factors for AKI including treatment with cisplatin itself and an underlying diagnosis of metastatic cancer. Guidance from National Library of Medicine states this is associated with AKI.

63. Mr E’s admission notes from 11 February do not identify other common triggers for AKI such as infection (no fever) nor administration of nephrotoxic drugs. He was not taking oral diuretics, did not report diarrhoea or vomiting and was not judged to be clinically dehydrated on examination.

64. Our nephrology adviser explained many episodes of AKI are considered to be caused by several factors and it is often difficult to identify a single cause. The direct impact of 500ml of mannitol on Mr E’s kidney function and therefore on the development of AKI, is difficult to determine, and there are other factors which may have had a larger effect.

65. Mr E had received previous cisplatin-based treatment in 2021 according to his records and there is no indication that he developed AKI on that occasion. The treatment on 4 February was his first dose of a new course of treatment, and the time scale (AKI diagnosed seven days later) is compatible with that usually described for cisplatin induced AKI.

66. Our nephrology adviser explained whilst Mr E received a larger dose of mannitol than had been prescribed, this would still have been a therapeutic dose in other circumstances. There are other likely significant contributing factors to the onset of his AKI, specifically the administration of cisplatin.

67. The medical records show the unintended administration of the higher dose of mannitol was recognised during Mr E’s treatment on 4 February and he was reviewed by a resident doctor who provided advice to drink plenty of fluids and to be aware that Mr E would experience increased urination. Mrs E was also informed of the mannitol dose error whilst her husband was receiving his chemotherapy.

68. At the time that Mr E received the unintended increased dose of Mannitol, the resident doctor sought advice from the pharmacist and performed blood tests to re-check his kidney function. These actions were consistent with NICE AKI guidance on recognising patients at high risk of AKI which states:

• ‘1.1.1 investigate for acute kidney injury, by measuring serum creatinine and comparing with baseline, in adults with acute illness if any of the following are likely or present [inc. use of drugs that can cause or exacerbate kidney injury]’ and ‘1.2.13 Seek advice from a pharmacist about optimising medicines and drug dosing in adults, children and young people with or at risk of acute kidney injury’

69. Mr E was reviewed by his oncologist on 9 February who noted that he was experiencing mild nausea. The oncologist apologised for the mannitol dose error. Mrs E received telephone support from the uro-oncology (specialised field focusing on the diagnosis and treatment of cancers affecting the urinary system) team. The consultation focused on his increasing flank/leg pain.

70. The records show that communication with Mr and Mrs E following the mannitol administration error was consistent with GMC advice on openness and honesty when things go wrong.

71. Mr E’s subsequent readmission to hospital with recurrent AKI on 25 March 2022, occurring without re-exposure to mannitol and on this occasion proven to be due to obstruction, is indicative of the complexity of his illness and his vulnerability to AKI because of advanced cancer.

72. We cannot say the mannitol overdose contributed to Mr E developing AKI. The dose of mannitol which he received was within the range used therapeutically. Other factors may have contributed to the AKI.

Pain and pain management

73. Mrs E explained the overdose of mannitol led to her husband experiencing significant pain and distress which she feels could have been avoided, and this pain was not managed effectively. She says because of the AKI, Mr E had to take opioid drugs and fentanyl, which she says caused him to suffer further.

74. Mr E experienced a significant amount of pain during the final few months of his life. During a telephone consultation with the oncology clinic 21 January, he reported new left flank pain, accompanied by suprapubic swelling (a visible lump in the lower, central abdomen, just above the pubic bone), and these symptoms persisted thereafter.

75. When Mr E was admitted to hospital 11 February, he was noted to have isolated oedema (swelling due to fluid build up) of the left leg.

76. Our nephrology adviser explained the cause of Mr E’s left flank pain and leg oedema was thoroughly investigated but the causes remained uncertain.

77. Mr E underwent CT scans on 15 December 2021, 30 January, and 11 February 2022. Additionally, he underwent MRI scans of the lumbar-sacral spine on 14 February, and of the pelvis on 17 February as well as a doppler ultrasound which excluded left leg deep vein thrombosis (DVT).

78. A MAG-3 renogram (a nuclear medicine scan that evaluates kidney function and urine drainage from the kidneys to the bladder, helping detect obstructions or delayed drainage) was carried out on 15 February, and a further KUB ultrasound (a KUB ultrasound is a safe, non-invasive imaging test that evaluates the kidneys, ureters, and bladder to detect abnormalities such as stones, infections, tumours, or structural changes) was performed on 16 February.

79. The CT scans demonstrated relatively small but enlarged lymph nodes within the abdomen and pelvis, including an enlarged left iliac lymph node (inflammation). The CT scans did not demonstrate evidence of bony metastases which might have been an explanation for worsening pain. The bladder and the sigmoid colon both appeared thickened, which was thought to possibly reflect previous radiotherapy.

80. The MRI scan of the spine suggested that there were very small metastatic cancer deposits in two vertebrae, but these were felt unlikely to be the cause of pain. The MRI also demonstrated degenerative changes in the spine affecting the nerve roots.

81. Our nephrology adviser explained compression of these nerve roots would be likely to produce pain in lower leg and foot whereas Mr E’s pain was in his upper leg. In view of the divergence between MRI findings and the location of Mr E's symptoms, he went on to have an MRI to look at the left side of the pelvis.

82. The MRI scan of the pelvis demonstrated swelling of the left iliopsoas muscle (composite muscle of the inner hip), sigmoid colon (final segment of the large intestine) and left pelvic sidewall, this is consistent with the effects of previous radiotherapy.

83. A palliative care consultant who saw Mr E on 4 March concluded his pain was likely to be multifactorial with neuropathic features, the effects of lymphedema (swelling caused by fluid in the tissues) and possibly contributions from enlarged retroperitoneal and pelvic lymph nodes and degenerative spinal disease.

84. Mr E’s case was reviewed by the London Urology Cancer MDT on several occasions, including 11 March when his imaging and symptoms were reviewed. The MDT on this occasion recorded that his back pain was likely due to degenerative disease rather than spinal metastases and that the lymphedema was due to previous radiotherapy rather than bulky lymphadenopathy (refers to the presence of unusually large lymph nodes or tumour masses).

85. Our nephrology adviser explained AKI of the type which Mr E developed does not typically cause flank pain. Similarly, flank pain is not a commonly reported side effect of the administration of mannitol.

86. Taking into consideration the extensive investigations undertaken and the conclusion of the palliative care consultant who reviewed Mr E, the medical records do not show the administration of 500ml mannitol led to Mr E experiencing significant pain which could have been avoided, nor was this the reason he had to take opioid drugs.

87. Mr E’s health appeared to deteriorate quickly from early February 2022 and the records indicate that he was in considerable pain despite careful management of this.

88. Both factors were likely to have caused him significant distress. The records reflect that this was understandably, also a very distressing time for Mrs E.

89. Mr E was referred to the palliative care team during his admission to hospital on 11 February.

90. The palliative care team frequently reviewed him during, between and after his hospital admissions in February and March 2022. Mr and Mrs E were also supported by the Uro-oncology CNS team with frequent interactions and reviews which focused on a holistic approach to his care, including updates on his symptom control.

91. His pain medications were adjusted regularly in response to the level of pain control he was achieving and taking account of his reduced kidney function.

93. GMC guidance on treatment and care towards the end of life states:

• ‘The people close to a patient can play a significant role in ensuring that the patient receives high-quality care as they near the end of life, in both community and hospital settings.

• It is important that you and other members of the healthcare team acknowledge the role and responsibilities of people close to the patient. You should make sure, as far as possible, that their needs for support are met and their feelings respected, although the focus of care must remain on the patient.’ And • ‘You must seek advice or a second opinion from a colleague with relevant experience (who may be from another specialty, such as palliative care)’

92. Mr E received care based on a multi-disciplinary and multi-professional model consistent with the above GMC guidance. The Trust provided ongoing involvement and support for Mrs E, and sought advice from specialist teams, including the palliative care team in this case.

93. We find that Mr E was well supported by the multi-disciplinary team during the last few months of his life and that his pain was appropriately managed despite difficulty in achieving effective pain relief.

94. We appreciate Mr E experienced significant pain in the last few months of his life. We recognise the distress this caused him and Mrs E. We cannot say the mannitol overdose caused this pain, or directly meant he required opioid drugs.

Chemotherapy and immunotherapy

95. Mrs E says if her husband had not been given the mannitol overdose, he could have been treated with further chemotherapy and immunotherapy. She says he had responded well to chemotherapy previously and she feels he would have lived for longer and would not have suffered if treatment could have continued. She says his opportunity to be treated was denied due to his AKI.

96. Mr E was diagnosed with transitional cell cancer of the bladder in January 2021. The cancer had already invaded the wall of the bladder and involved regional lymph nodes at the time of diagnosis. He underwent chemotherapy and radical radiotherapy.

97. His condition was complicated by a heart attack, and he underwent coronary artery bypass graft surgery (a surgical procedure that creates a new path for blood to flow to the heart by bypassing blocked arteries, improving blood flow, and reducing symptoms of coronary artery disease) in June 2021.

98. Unfortunately, a planned repeat CT scan in December 2021 indicated Mr E’s cancer had returned with enlarged lymph nodes (small glands that are part of the lymphatic system which helps the body fight infections) in his chest, abdomen, and pelvis.

99. He was then offered palliative chemotherapy with gemcitabine and cisplatin (a chemotherapy combination) plus atezolizumab immunotherapy (used to enhance the immune system’s ability to attack cancer cells). His oncologist documented the palliative intent of his treatment in his records.

100. On 12 January, Mr E’s oncologist advised him that the prognostic implications of recurrent cancer were serious and that average life expectancy in this situation was two years.

101. The Trust administered Mr E’s first dose of gemcitabine and cisplatin on 4 February. His health then subsequently deteriorated. The second dose of chemotherapy should have been administered on 11 February but was deferred due to his AKI.

102. Mr E’s kidney function improved partially, and he received a further dose of chemotherapy on 25 February. Mannitol was not administered on this occasion.

103. The plan from the oncologist was that Mr E continue with carboplatin and gemacitabine chemotherapy, but his health worsened and he was readmitted to hospital on 25 March with suspected infection and recurrent AKI.

104. In early April, whilst still in hospital, Mr E was found to have developed malignant ascites (abnormal accumulation of fluid in the abdomen caused by cancer, often indicating advanced or metastatic disease). Although his kidney function improved following insertion of nephrostomies, his general condition had deteriorated to the extent that he was too unwell for further chemotherapy. The focus of his care switched to end of life care.

105. As described above, the records to do not conclusively demonstrate Mr E developed AKI because of receiving mannitol. It is likely that he developed AKI through multifactorial causes, including, and probably most significantly, through cisplatin treatment. Our nephrology adviser explained had Mr E not suffered AKI in February, he may well have completed more of his planned chemotherapy treatment. It is not possible to say, however, that continuing chemotherapy would necessarily have altered his outcome.

106. Based on the medical records and on the balance of probabilities, it is our view that Mr E’s cancer might have continued to progress rapidly even if he had been able to receive more chemotherapy. It is not possible to say that had Mr E received mannitol in the dose prescribed, and even had he not developed AKI irrespective of its cause, that his life would have been prolonged by more cancer treatment.

High blood pressure

107. Mrs E also stated because of the mannitol overdose Mr E had consistently high blood pressure which led to a heart attack.

108. Our adviser explained the medical records do not suggest that the administration of mannitol caused Mr E to develop high blood pressure.

109. In line with NICE guidelines, hypertension is not a recognised direct complication of mannitol administration. If someone suffered excessive diuresis after receiving mannitol, they might become hypotensive through dehydration.

110. Mr E’s blood pressure was normal in January 2022 as documented in the medical records, and he was not taking anti-hypertensive medication at this time. He was taking a small dose of ramipril (a medication used to reduce the risk of cardiovascular events) for impaired LV function (occurs when the heart’s main pumping chamber cannot efficiently pump or fill with blood, leading to heart failure symptoms and reduced cardiac output).

111. Frequent blood pressure measurements were made during Mr E’s hospital admission in February, and these were also largely normal.

112. Mr E’s blood pressure was mainly normal during his second admission from 25 March. Mr E was not treated with anti-hypertensive medication during either the February or March 2022 admissions.

113. The medical records show Mr E had suffered a heart attack in June 2021 and underwent coronary artery bypass surgery in September 2021. The cardio-renal MDT discussed Mr E’s case and concluded that his heart attack was most likely to be result of pre-existing coronary artery disease, and not due to cancer treatment.

114. It is our view that the mannitol overdose did not cause Mr E’s high blood pressure.

115. We cannot link the failing we have identified to Mrs E's claimed impact. We can however say Mrs E would have experienced an element of distress and uncertainty at the time the mannitol overdose was administered.

1. Mrs E complains about aspects of care and treatment University College London Hospitals NHS Foundation Trust (the Trust) provided to her husband, Mr E between December 2021 and April 2022.

2. We found the Trust did not delay reporting Mr E’s scan results in December 2021.

3. We have also found the Trust gave Mr E an overdose of mannitol on 4 February 2022.

4. We cannot link the overdose of mannitol with the impact Mrs E claims. We can say Mrs  E experienced a degree of distress and uncertainty due to the Trust’s actions.

5. We partly uphold this complaint and have set out the recommendations we have made at the end of this report.

116. These are the recommendations we are making.

117. Our Principles state that public organisations should put things right and, if possible, return the person affected to the position they would have been in if the poor service had not occurred. If that is not possible, they should compensate them appropriately.

118. To decide on a level of financial remedy, we review similar cases where the person has experienced similar injustice, along with our severity of injustice scale. Following this review, we consider the Trust should pay Mrs E £400 in recognition of the distress and uncertainty during the time the mannitol overdose happened as she did not know if this had an impact on Mr E’s condition and prognosis.

119. We ask that it does this within four weeks of the date of our final report.

120. We are reassured to see that the Trust has put service improvements in place.

121. Following the mannitol overdose administration, the team followed duty of candour policy and reported the incident appropriately. There is documented evidence of recognition of the error and apologies from several team members, including the consultant. New equipment had been ordered to prevent a similar issue arising.

122. As action has been taken to remedy the failings because of Mrs E’s complaint, we will not be recommending service improvements in this case.