Prevention of Future Deaths reports · 2021

Ann Coles

Regulation 28 report to prevent future deaths, reference 2021-0101, written 13 Apr 2021. A coroner writes one of these when an inquest reveals a risk that could cause further deaths unless something changes.

Date of report13 Apr 2021
Reference2021-0101
DeceasedAnn Coles
CoronerCaroline Topping
Coroner areaCounty of Surrey
CategoryAlcohol, drug and medication related deaths · Hospital Death (Clinical Procedures and medical management) related deaths
Sourcejudiciary.uk record · original PDF
Responses published3

The report

Text extracted from the PDF text layer. Reproduced verbatim, including the scan's own layout.

IN THE SURREY CORONER’S COURT 

IN THE MATTER OF: ANN COLES  

__________________________________________________________ 

The Inquest Touching the Death of ANN COLES  

A Regulation 28 Report – Action to Prevent Future Deaths 

__________________________________________________________ 

THIS REPORT IS BEING SENT TO: 

• 
• 

Practitioners  

1 

CORONER 

, President of the Royal College of Physicians  

, President of the Royal College of General 

Caroline Topping, HM Assistant Coroner for the County of Surrey 

2 

CORONER’S LEGAL POWERS 

I make this report under paragraph 7, Schedule 5, of the Coroners and Justice Act 2009 
and Regulations 28 and 29 of the Coroners (Investigations) Regulations 2013. 

3 

INVESTIGATION and INQUEST 

An investigation into the death of Ann Coles was opened on the 4th April 2019. The 
Inquest was opened on 12th November 2019 and resumed and concluded on 16th March 
2021. 

I concluded that Ann Coles was admitted to Frimley Park Hospital suffering with severe 
bilateral pneumonia and sepsis. Despite appropriate treatment she developed multi-
organ failure and died on the 12th March 2019. The cause of death was: 

I a Multiple Organ Failure 
I b Sepsis 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 I c Pneumonia 
II Aortic Stenosis  

I concluded she died of natural causes  

4 

CIRCUMSTANCES OF THE DEATH 

Ann had a tissue aortic valve replacement in 2014 having been diagnosed with severe 
aortic stenosis. She developed atrial fibrillation after the operation and required 
medication to revert to sinus rhythm. Thereafter she was prescribed amiodarone to 
prevent her relapsing into atrial fibrillation. She was subject to annual reviews thereafter. 
In March 2019 she was admitted to Frimley Park Hospital suffering with shortness of 
breath and found to have developed pneumonia. Despite appropriate treatment she died 
from multi-organ failure on the 12th March 2019.  

5 

CORONER’S CONCERNS 

During the course of the inquest the evidence revealed matters giving rise to concern. In 
my opinion there is a risk that future deaths could occur unless action is taken. In the 
circumstances it is my statutory duty to report to you. 

The MATTERS OF CONCERN are as follows.  –  

The evidence showed that a potential side effect of amiodarone medication is 
that it can cause toxicity which effects the lungs and can cause fibrotic changes. 
In her evidence the consultant cardiologist who treated Ann in her final illness 
raised the concern that there is no requirement for lung imaging to be 
undertaken when patients are prescribed amiodarone on a long term basis 
which in her view was a glaring gap in the oversight necessary for the effects of 
the medication.  

.  

6 

ACTION SHOULD BE TAKEN 

In my opinion action should be taken to prevent future deaths and I believe your 
organisation has the power to take such action.  

7 

YOUR RESPONSE 

You are under a duty to respond to this report within 56 days of the date of this report, 
namely by 8th June 2021. I, the coroner, may extend the period. 

Your response must contain details of action taken or proposed to be taken, setting out 
the timetable for action. Otherwise you must explain why no action is proposed. 

 
 
 
 
 
 
 
 
 
 
 8 

COPIES and PUBLICATION 

I have sent a copy of my report to the Chief Coroner and to the following Interested 
Persons;  

 and Frimley Park Hospital  

I am also under a duty to send the Chief Coroner a copy of your response.  

The Chief Coroner may publish either or both in a complete or redacted or summary 
form. He may send a copy of this report to any person who he believes may find it useful 
or of interest. You may make representations to me, the coroner, at the time of your 
response, about the release or the publication of your response by the Chief Coroner. 

9 

Signed: 

Caroline Topping 

Dated this 13th April 2021.

Responses

3 responses published against this report on judiciary.uk. A response is a body's written reply to the coroner's concerns; publication is at the discretion of the Chief Coroner's office, so an absent response does not mean nobody replied.

Response from Mhra (PDF)
PA to HM Coroner for Surrey 

HM Coroner’s Court 
Station Approach 
Woking 
Surrey 
GU22 7AP 

3rd August 2021 

Dear 

, 

Medicines & Healthcare products 
Regulatory Agency 

10 South Colonnade  
Canary Wharf  
London  
E14 4PU 
United Kingdom 

gov.uk/mhra 

Regulation 28 Report to Prevent Future Deaths concerning Ann Coles 

Thank you for your e-mail of 21 June 2021 regarding a Regulation 28 Report to Prevent Future Deaths 
following the inquest into the death of Ann Coles. The report raised a matter of concern that there is no 
requirement for lung imaging to be undertaken when patients are prescribed amiodarone on a long term 
basis;  the  consultant  cardiologist  who  treated  Ann  considered  this  was  a  glaring  gap  in  the  oversight 
necessary for the effects of the medication. 

The  Medicines  and  Healthcare  products  Regulatory  Agency  (MHRA)  is  the  executive  agency  of  the 
Department of Health and Social Care (DHSC) with responsibility for the regulation of medicinal products 
in the UK. The MHRA ensures that medicines are efficacious and acceptably safe, and that any possible 
side effects which have been recognised to occur with use of a medicine are appropriately described in 
the  authorised  product  information.  This  comprises  the  Summary  of  Product  Characteristics  (SmPC, 
intended for healthcare professionals), labelling, and Patient Information Leaflet (PIL, provided to patients 
in each medicine pack). 

Amiodarone is an effective medicine for the management of arrhythmia, but it is known to be associated 
with  a  number  of  serious  unwanted  effects  in  several  organ  systems  including  the  eyes,  nerves,  skin, 
thyroid, gastrointestinal, lung, heart, and liver. The product information for amiodarone therefore contains 
extensive  warnings  and  precautions  for  use,  patients  must  be  monitored  closely  during  treatment,  and 
treatment should be initiated and monitored only under hospital or specialist supervision. Additionally, due 
to its toxicity, the use of amiodarone is now reserved only for the treatment of severe rhythm disorders not 
responding to other therapies or when other treatments cannot be used.  

Amiodarone is available as an oral tablet and as a solution for intravenous (IV) infusion. The SmPC for 
both formulations describes the symptoms of pulmonary toxicity (i.e. onset of shortness of breath or non-
productive cough). The incidence of pulmonary toxicity is known to be lower with IV formulations (where it 
is  reported  very  rarely,  affecting  fewer  than  1  in  10,000  patients)  than  for  oral  formulations  (reported 
commonly, affecting between 1 in 10 and 1 in 100 patients). The SmPC for oral amiodarone notes that 
onset is usually slow but may be rapidly progressive and whilst the majority of cases have been reported 
with long term therapy, a few have occurred soon after starting treatment.  

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 The  product  information for  oral  amiodarone  also  suggests  that  consideration  be  given to  chest  X-rays 
before  starting therapy, and  if  pulmonary toxicity  is  suspected, this  should be repeated  and  associated 
with lung function testing including, where possible, measurement of transfer factor. For IV amiodarone 
chest X-rays are recommended only when a diagnosis of interstitial pneumonitis is suspected. The PIL 
reflects  this  information  in  patient-friendly  language,  and  section  4  (side-effects)  of  the  PIL  for  oral 
amiodarone  generally  instructs the  user to  stop  treatment  and  see  a  doctor  or  go to  a  hospital  straight 
away if they experience worsening of respiratory symptoms (which may be common). 

The MHRA has conducted a review of this issue and sought independent expert advice on the matter of 
concern from the Commission on Human Medicines’ Pharmacovigilance Expert Advisory Group (PEAG); 
written advice was also sought from the CHM’s Cardiovascular, Diabetes, Renal, Respiratory and Allergy 
Expert Advisory Group (CDRRA EAG). The PEAG noted that the question of regular pulmonary monitoring 
has been well considered over many years, but the risks (especially radiation exposure from performing 
high-resolution computerised  tomography [CT]  scans)  are  thought  likely  to far  exceed  any  benefit.  The 
PEAG also noted that repeated chest X-rays can cause anxiety for patients.  

For these reasons, the PEAG did not consider regular chest imaging was advisable or necessary, given 
that patient-reported worsening of respiratory function is usually the first indicator of pulmonary toxicity. 
Nevertheless,  the  PEAG  considered  that  there  was  scope  for  improvement  in  the  product  information, 
particularly with respect to the PIL on the seriousness of pulmonary toxicity and the fact this may happen 
at any time during treatment.  

The  PEAG  also  discussed  whether  additional risk minimisation  measures  such as  a  Patient  Alert  Card 
would help to inform patients of the risks of treatment and symptoms to be aware of. The PEAG considered 
that it would be useful to issue a reminder to healthcare professionals on the risks associated with use of 
amiodarone,  the  need  for  monitoring  of  patients,  that  patients  should  be  informed  and  aware  of  the 
symptoms  of  pulmonary  toxicity,  and  that  any  such  symptoms  should  be  reported  promptly  (and 
investigated). The PEAG considered that an article in the MHRA’s monthly ‘Drug Safety Update’ bulletin 
may be an appropriate method to communicate these messages.  

The  MHRA  will  now  take  forward  these  recommendations.  For  information,  Ms  Cole’s  case  has  been 
.  
recorded on our adverse drug reaction database with the Yellow Card reference number 

I will keep you updated on progress, but in the meantime, we will continue to keep the safety of amiodarone 
under close review. 

Yours sincerely, 

Chief Executive 
Medicines and Healthcare products Regulatory Agency
Response from Royal College of General Practitioners (PDF)
RC Royal College of
G P General Practitioners

Dr
Joint Honorary Secretary

Ms Caroline Topping

Se

26 May 2021

Dear Ms Topping,

Regulation 28 Report to Prevent Future Deaths - touching on the death of Ann Coles

Thank you for your report of 13 April 2021. | am responding on behalf of the Royal College of
General Practitioners as Joint Honorary Secretary to Council. Firstly, can | convey our
condolences to the family and friends of Ann Coles. | was saddened to read of Ann's passing.

The Royal College of General Practitioners (RCGP) is the largest membership organisation in the
United Kingdom solely for GPs. It aims to encourage and maintain the highest standards of
general medical practice and to act as the ‘voice’ of GPs on issues concerned with education;
training; research; and clinical standards. Founded in 1952, the RCGP has just over 54.000
members who are committed to improving patient care, developing their own skills and
promoting general practice as a discipline.

| observe that a matter of concern from your inquest is as follows:

The evidence showed that a potential side effect of amiodarone medication is that it can cause toxicity
which effects the lungs and can cause fibrotic changes. In her evidence the consultant cardiologist who
treated Ann in her final illness raised the concern that there is no requirement for lung imaging to be
undertaken when patients are prescribed amiodarone on a long term basis which in her view was a
glaring gap in the oversight necessary for the effects of the medication.

By way of background, a number of medications are used to control the rhythm of the heart,
most commonly beta blockers and calcium channel blockers. Amiodarone is a medication that
has been used for many years and whilst effective, is known to have a range of short and longer
term side effects. Details can be accessed in the British National Formulary here Given these
side effects it considered to be at least a second or third line drug and for this reason, would be

Royal College of General Practitioners

30 Euston Square, London, NW1 2FB
rcgp.org.uk
Patron: HRH The Duke of Edinburgh (1972-2021) | Registered Charity Number 223106

initiated by a cardiologist or consultant physician, who would frequently then monitor the
patient on a regular basis.

Areview of the evidence shows that the respiratory side effects of amiodarone can be relatively
frequent - about 5%, with higher doses making side effects more common (see here). The
British National Formulary makes a recommendation regarding the regular assessment of thyroid
function and that the patient should have a Chest X Ray prior to starting treatment with
amiodarone. There is no other recommendation regarding the ongoing monitoring of lung
function or a periodic chest X Ray.

The Royal College of General Practitioners is not a regulating organisation and especially not for
medication although we do have responsibilities in guiding standards and providing education.
Regulatory responsibility of medication lies with The Medicines and Healthcare products
Regulatory Agency (MHRA). Given the concerns raised in your inquest, | recommend that you
request the MHRA comment upon this matter. Contact details are here.

I trust that this reply is helpful and if you have any questions, please do not hesitate to contact
me.

Yours sincerely,

k

Joint a — a Council

Royal College of General Practitioners

Cc: Professor | i of the Royal College of Physicians
Response from Royal College of Physicians (PDF)
From the Registrar 

Dr 

. 

Royal College of Physicians 
11 St Andrews Place 
Regent’s Park 
London NW1 4LE 

www.rcplondon.ac.uk 

Ms Caroline Topping  
HM Coroner’s Court  
Station Approach  
Woking  
Surrey  
GU22 7AP  

27 May 2021 

Dear Ms Topping, 

Re: Regulation 28 – Ann Coles  

Issued:    
Received:  
Responded:  

13 April 2021 
13 April 2021 
27 May 2021 

Thank you for sending your Section 28 notice to the President of the Royal College of Physicians. This reply is 
on behalf of the organisation following consultation with appropriate officers and partners. In particular we 
have consulted with three experts in the British Cardiovascular Society and British Heart Rhythm Society. 

Summary of response 

Having reviewed the detail, the RCP would recommend that no new systems of monitoring and reporting are 
required for the prescription of amiodarone but that strict adherence to existing national NICE and local 
shared care guidelines will provide for safe and monitored practice. 

Details of Response 

Matters of Concern  
“The evidence showed that a potential side effect of amiodarone medication is that it can cause toxicity which 
effects the lungs and can cause fibrotic changes. In her evidence the consultant cardiologist who treated Ann 
in her final illness raised the concern that there is no requirement for lung imaging to be undertaken when 
patients are prescribed amiodarone on a long-term basis which in her view was a glaring gap in the oversight 
necessary for the effects of the medication”.  

Pulmonary toxicity is a well-recognised side effect of amiodarone and it is considered to be “common” in the 
British  National  Formulary.  Guidance  in  October  2020,  from  the  National  Institute  for  Health  and  Care 
Excellence (NICE), Amiodarone – not initiated in primary care  1 is clear that this drug should have  limited 
indications and reasserts how it should be initiated and then monitored.  

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 Re: Regulation 28 – Ann Coles  

Before  starting  treatment,  patients  should  have  a  chest  x-ray  but  there  is  no  requirement  for  routine 
pulmonary monitoring thereafter. The emphasis is one of ongoing drug review and if pulmonary toxicity is 
suspected then immediate specialist review. The focus should be on shared care guidelines agreed between 
local hospital trusts and their primary care clinical commissioning groups.  

The  RCP  recommends  adherence  to  such  shared  care  guidelines  and  that  arrangements  for  review  of 
medications are in line with the recent NICE guidance (link below). 

https://cks.nice.org.uk/topics/atrial-fibrilaation/prescribing-information/amiodarone-not-initaited-in-
primary-care/  

We hope that these recommended actions will help prevent future problems of this nature. 

Yours Sincerely, 

Dr 
Registrar, Royal College of Physicians

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