Management of an acute painful sickle cell episode in hospital: summary of NICE guidanceBMJ 2012; 344 doi: https://doi.org/10.1136/bmj.e4063 (Published 27 June 2012) Cite this as: BMJ 2012;344:e4063
All rapid responses
Two points, if I may:
1. This article could have usefully mentioned that Sickling is also found in Greece and India (though not commonly).
2. Konotey-Ahulu challenged the use of diamorphine. This could be described as a matter of life and death.
Could NICE please tell us what the present recommendations are?
Competing interests: Curiousity
Management of acute painful sickle cell episode in hospital: NICE guidance is frightening!
If this NICE Guidance (July 21, page 48)  is a response to my frequent queries on mounting deaths of hospitalized sickle cell disease (scd) patients [2-8] it frightens me.
The National Confidential Enquiry into Patient Outcome and Death (NCEPOD)  found that between 1 January 2005 and 31 December 2006 “Nine out of the 19 patients with sickle cell disease who had pain on admission and who then died had been given excessive doses of opiods” 
Since 1991 I have asked: “Why should West Indians and West Africans who did without morphine in their countries be put on morphine pumps when they were admitted to UK hospitals?” [7 11] Haematologists would not give Diamorphine to their daughters for severe dysmenorrhoea  yet scd patients are prescribed it? .
One Consultant Physician commented “You Haematologists have created a cohort of addicts in this hospital!” , so how would this GUIDANCE help both Consultants look after the same scd patients? I described “a woman who had been on continuous opiate infusion” for 6 months in an NHS hospital. . How could this NICE Guidance help her?
BMJ’s 11 Rapid Responses  to NCEPOD REPORT included one from a Ghanaian Professor whose 31 year old son [‘SC’] walked into a Manchester hospital to die within 3 days , and a Ghanaian mother whose 32 year old [‘SC’] daughter walked to hospital with chest pain and breathlessness died within 18 hours  A commonsense approach is all that is needed [4 16 17 18] whether in Ghana  or Jamaica under Graham Serjeant  who once said “In Jamaican experience morphia or its derivatives are rarely used or necessary”  and that “the most painful crises may be treated in a day-care centre, the patient returning home in the evening”  – a different approach entirely from the UK opiod protocol of Sally Davies and Lola Oni .
When an English Physician who would not give Diamorphine to scd patients .was called “racist” by one Haematologist I responded: “White physicians who, at the risk of being misunderstood by (named haematologist), voice their displeasure at what they see happening on their wards deserve commendation, not condemnation”. 
With our “combined experience of 80 years covering thousands of patients in sickle cell crisis”  Serjeant and I have no need of NICE or NIH Guidelines espoused by some haematologists . One of Serjeant’s never been transfused patients, died in the USA after transfusion [7 25], highlighting international differences in patient management. Heroin (Diamorphine) “has no accepted medical use in the United States”  yet NICE quotes the NIH as if it supports British practice.
OVERSEAS PATIENTS AND RELATIVES
Clinical experience  not haematological experience is what saves patients’ lives. Stopping opiod infusions in Washington, Maine, and Geneva got patients out of bed the very next day . Opiods can mask serious pathology like ectopic pregnancy, bronchopneumonia, and cerebral malaria diagnosed only after autopsy in the scd patient just returning from holiday abroad [29 30]
SICKLE CELL DISEASE AND SICKLE CELL DISEASE PATIENT
“Treating Sickle Cell Disease” is not the same as “Managing the Sickle Cell Disease Patient” [17 31]. One in 4 male scd patients from Ghana has G6PD Deficiency  Ciprofloxacin given for the urinary tract infection or pneumonia that precipitated crisis could do harm. What says NICE about G6PD Deficient scd patients in painful crisis?
IS TRADE THE REAL REASON FOR USING OPIODS FOR SICKLE CELL PAIN?
Professor Elisabeth Goodman found KETOROLAC as efficient as morphine for controlling pain in sickle cell crisis but without the latter’s respiratory depression . “So why do British Haematologists prefer to use morphine and diamorphine?” . Three UK Haematologists gave this answer: “Ketorolac has no product license in the UK for this indication” . Ringelhann and I are convinced that the chest syndrome in the UK and the USA is due to the “routine use of opiates for sickle cell crises” , while one UK haematologist “was concerned that narcotic analgesics could contribute to development of the sickle cell chest syndrome in patients hospitalized for painful crises” . If relatives sued for opiate related deaths could NICE Guidance be used as plea in Court?
BBC NEWSNIGHT REPORTS ON HEROIN ADDICTION ADD TO CONCERN
On Newsnight August 9 and 10 2012 and BBC 4 “Crossing Continents” August 10 Heroin Addiction was covered. As I watched and listened I thought to myself “And this is the drug that NICE has recommended be given as ‘bolus injection’  to someone in sickle cell pain crisis?”
1. Compile a register (a) of excellent Family Practitioners who manage scd patients themselves with minimal reliance on hospitals; (b) of Consultants on whose wards patients do not die from opiods; and (c) of Community Nurses who often know more about scd patients than other health workers. One such – Marion McTair – plus an NHS Consultant Haematologist, and a GP cooperated with me to wean a scd youth “SS” from opiods and blood transfusions to go from ‘A’ Levels to PhD in Great Britain.
2. We need Haematologists to emulate Professor Maxwell Wintrobe MD whose History of Haematologists is a masterpiece 
3 Concentrate on Genetic Counselling [39 40], because “Unless we Africans are involved in genetic counseling and family size limitation here in the UK the genetic burden on the National Health Service will go up and up” 
4 NHS Hospitals must publish monthly Opiate bills on Sickle Cell Disease patients  because “Chest syndrome was always there to blame, if the patient died” .
Felix I D Konotey-Ahulu MD(Lond) DSc(UCC) FRCP(Lond) FRCP(Glasg) DTMH(L’pool) – Kwegyir Aggrey Distinguished Professor of Human Genetics, University of Cape Coast, Ghana and Consultant Physician Genetic Counsellor in Sickle Cell and Other Haemoglobinopathies, Phoenix Hospital Group, 9 Harley Street, London W1G 9AL.
1 Gillis VL, Senthinathan A, Dzingina M, Chamberlain K, Banks K, Baker MR, Longson D [Guideline Development Group]. Management of an acute painful sickle cell episode in hospital: summary of NICE guidance. BMJ 2012; 344: e4063 [doi:101136/bmj.e4063]
2 Konotey-Ahulu FID. UK drug related deaths are still rising: So where is NICE? BMJ Rapid Response to Susan Mayor on “UK drug related deaths are still rising 2 reports say”(BMJ Sept 6 2009) http://www.bmj.com/cgi/eletters/339/sep01_1/b3536#219836
3 Konotey-Ahulu FID. Current “hit and miss” care provision for sickle cell disease patients in the UK. http://www.bmj.com/cgi/eletters/337/jul11_2/a771#199135 BMJ Rapid Response 22 July 2008 to Susan Mayor on “Group publishes standards for adult sickle cell disease to reduce number of unexplained deaths” (BMJ 2008; 337:a771) http://www.bmj.com/cgi/eletters/337/jul11_2/a771
4 Konotey-Ahulu FID. Dedicated sickle cell teams. BMJ Rapid Response to Graham Serjeant’s “The case for dedicated sickle cell centres”. [BMJ 2007; 334: 477 (3 March)] http://www.bmj.com/cgi/eletters/334/7591/477#162678 [20 March 2007]
5 Dyer Clare. Inquest begins into deaths after concerns about diamorphine levels. BMJ 2009; 338: b903 [7 March]
6 Konotey-Ahulu FID. Inquest into diamorphine deaths; Does NCEPOD sickle cell patients report warrant a similar inquest? BMJ Rapid response 7 March 2010. http://www.bmj.com/cgi/eletters/338/mar03_3/b903#210208
7 Konotey-Ahulu FID. Poor care for sickle cell disease patients: This wake up call is overdue BMJ Rapid Response May 28 2008 BMJ 2008; 336: 1152 to Susan Mayor "Enquiry shows poor care for patients with sickle cell disease” on National Confidential Enquiry into Patient Outcome and Death (NCEPOD) REPORT "SICKLE: A Sickle Crisis?” (2008)
http://www.bmj.com/cgi/eletters/336/7654/1152a#196224 | http://firstname.lastname@example.org
8 Konotey-Ahulu FID. The politics (and economics) of pain relief in the West and Third World http://www.bmj.com/cgi/eletters/341/aug11_2/c3800#240684 24 Aug 2010 BMJ Rapid Response.
9 NCEPOD (National Confidential Enquiry into Patient Outcome and Death). Sickle: A Sickle Crisis? (2008) [Sebastian Lucas (Clinical Co-ordiantor), David Mason (Clinical Co-ordinator), M Mason (Chief Executive), D Weyman (Researcher), Tom Treasurer (Chaifman) email@example.com
10 Mason S. Enquiry shows poor care for patients with sickle cell disease. BMJ 2008; 336: 1152
11 Konotey-Ahulu FID. Morphine for painful crisis in sickle cell disease. BMJ 1991; 302: 1604 (29 June)
12 Konotey-Ahulu FID. Opiates for sickle cell crisis. Lancet 1998; 352: 651-52 (22 August)
13 Konotey-Ahulu FID. Opiates for sickle cell crisis? Lancet 1998; 351: 1438 (9 May)
14 Blankson EJ. Sickle cell disease is managed, NOT treated. BMJ Rapid Response 18 June 2008 http://www.bmj.com/cgi/eletters/336/7654/1152-a#197350
15 Shoetan Cecilia. I lost my Sickle Cell disease adult daughter minutes after being given Diamotrphine intravenously when she could not breathe. BMJ Rapid Response 3 June 2008 http://www.bmj.com/cgi/eletters/336/7654/1152-a#196520
16 Serjeant GR. The case for dedicated sickle cell centres. BMJ 2007; 334: 477 (3 March)
17 Konotey-Ahulu FID. Management of sickle cell disease versus management of the sickle cell disease patient. BMJ Rapid Response 17 September 2008. http://www.bmj.com/cgi/eletters/337/sep08_1/a1397#202088
18 Konotey-Ahulu FID. Clinicians facing conflicting recommendations: Use commonsense? http://www.bmj.com/cgi/eletters/337/nov28_2/a2530#205677
19 Konotey-Ahulu FID. The Sickle Cell Disease Patient. Natural History from a clinico-epidemiological study of the first 1550 patients of Korle Bu Hospital Sickle Cell Clinic. 1991/1992 The Macmillan Press Ltd, London and TA’D Co 1996, Watford, Hertfordshire WD17 3ZH Watford (645 pages) [Pages 469 to 517 contain 133 Illustrative Case Histories indicating that not once was Morphine or Diamorpjhine given for pain. An iv drip before a pain killer never failed to cutail severity of pain]
20 Serjeant GR. Sickle Cell Disease Oxford University Press (Second Edition) 1992. Oxford. (632 pages).
21 Serjeant GR. Sickle Cell Disease. Oxford. Oxford University Press, 1985, page 204.
22 Serjeant GR. Sickle cell disease. Lancet 1997; 350: 725-730.
23 Davies SC, Oni L. Management of patients with sickle cell disease. BMJ1997; 315: 656-660.
24 Claster Susan, Vichinsky Elliott P. Managing sickle cell disease. BMJ 2003; 327: 1151-1155. doi: 10.1136/bmj.327.7424.1151
25 Serjeant GR. Blood transfusion in sickle cell disease: A cautionary tale Lancet 2003; 361: 1659-60.
26 Ballas S K. Sickle Cell Pain. IASP Press. Seattle, USA, page 168.
27 Ranney Helen. “There is no single clinical experience in the United States comparable to that of Dr Konotey-Ahulu” In Summary of Symposium on Sickle Cell Disease – Diagnosis, Management, Education, and Research – In Sickle Cell Disease, Editors H Abramson, JF Berles, Doris Wethers (C. Mosby Co) 1972, page 320
28 Konotey-Ahulu FID. Malaria and sickle cell: “Protection?” Or “No Protection?” – Confusion reigns. http://www.bmj.com/cgi/eletters/337/oct01_3/a1875#203067 BMJ Rapid Response Oct 13 2008.
29 Konotey-Ahulu FID. Imported malaria in the UK: Unde venis? & Quo vadis? BMJ Rapid Response http://www.bmj.com/cgi/eletters/337/jul03_2/a135#198874 July 16 2008
30 Konotey-Ahulu FID. Sickle cell disease and the patient. Lancet 2005; 365: 382-83
31 Konotey-Ahulu FID. G6PD Deficiency in Ghanaians: How to recognize it.
http://blog.konotey-ahulu,com/blog/_archives/2008/1/16/3458557.html Jan. 16 2008
32 Goodman Elisabeth. Use of ketorolac in sickle cell disease and vaso-occlusive crisis. Lancet 1991; 338: 641-42.
33 Konotey-Ahulu FID. Opiates for pain in dying patients and in those with sickle cell disease. http://www.bmj.com/cgi/eletters/335/7622/685#177986 11 October 2007, BMJ Rapid Response
34 Liesner RJ, Vandenberghe EA, Davies Sally C. Analgeisics in sickle cell disease disease. Lancet 1993; 3411: 188.
35 Ringelhann B, Konotey-Ahulu FID. Hemoglobinopathies and thalassemias in Mediterranean areas and in West Africa: Historical and other perspectives 1910 to 1997 - A Century Review. Atti dell’Accademia dell Science di Ferrara ( Milan) 1998;74: 267-307
36 Liesner RJ, Vandenberghe EA. Sudden death in sickle cell disease. Journal of Royal Society of Medicine 1993; 86: 484-485.
37 Wintrobe MM. Clinical Hematology. Lea & Febiger, Philadelphia, 1968, 755 pages.
38 Wintrobe MM. Hematology: The Blossoming of a Science – A Story of Inspiration and Effort. Lea & Febiger, Philadelphia, 1985. [Distinguished Professor Max Wintrobe pointedly included me, a physician, to draw attention to the fact that the whole patient, not just their blood, was what Haematology was all about [pages 378-380]
39 Konotey-Ahulu FID. Sickle Cell Disease: The Case for Family Planning. Accra. ASTAB Books, Ltd 1973; 32 pages.
40 Boyo AE, Cabannes R, Conley CL, Lehmann H, Luzzatto L, Milner PF, Ringelhann B, Weatherall DJ, Barrai I, Konotey-Ahulu FID, Motulsky AG. Scientific Group on Treatment of Haemoglobinopathies and Allied Disorders. (Technical Report) 1972; 509 – 83 pages.
41 Konotey-Ahulu FID. Need for ethnic experts to tackle genetic public health. Lancet 2007; 370: 1836 doi:10.1016/50140-6736(07)61771-1
42 Konotey-Ahulu FID. Management of patients with sickle cell disease. African Journal of Health Sciences 1998; 5: 47 [Commenting on article of Sally Davies and Lola Oni (BMJ 315: 656 -60) "what I feel is more important in the day to day management of patients with a view to keeping them out of hospital, is clinical epidemiology which includes the circumstances of crises. Two examples suffice to illustrate what I mean: ... I fear Davies and Oni’s statement that ‘The Central Middlesex management protocol uses morphine infusions’ will make morphine the accepted drug for sickle crisis management. The consequences of such an approach are dire, especially when some UK hospitals are already making diamorphine their first choice"]
43 Konotey-Ahulu FID. Sickle Cell Disease In Successive Ghanaian Generations For Three Centuries (Manya Krobo Tribe). In The Human Genome Diversity Project: Cogitations of an African Native. Politics and the Life Sciences (PLS) 1999, Vol 18: No 2, pp 317-322. [Invited Commentary on Professor David Resnik's article: “The Human Genome Diversity Project: Ethical Problems and Solutions”] PMID: 12561789 [PubMed – indexed for MEDLINE] The named patients are marked ‘R’ denoting hereditary cold season ‘Rheumatism’ on this: http://www.konotey-ahulu.com/images/generation.jpg or http://www.sicklecell.md/images/generation.jpg
Competing interests: Competing interests: I am one of my parents’ 11 children 3 of whom had sickle cell disease so I constantly probe how sickle cell disease patients are managed or mismanaged. We have traced the hereditary ailment in my forebears generation by generation back to 1670 AD http://www.konotey-ahulu.com/images/generation.jpg
In response to Mr Patel, we are grateful that he has highlighted evidence to support the use of incentive spirometry in the prevention of pulmonary complications in sickle cell disease. However, the scope of this guideline was limited to the management of the painful crisis. The management of acute complications was not in the scoping document for this guideline.
In reply to Mr Shin, infectious causes of sickle cell crisis were also considered out of the scope of the guideline following the referral from the Department of Health. The referral of the guideline was specifically about the management of sickle cell crisis whilst in hospital.
I hope this clarifies things.
Professor Damien Longson.
Links: Remit - http://guidance.nice.org.uk/CG/Wave24/6/Remit/pdf/English
Competing interests: No competing interests
Gillis et al’s summary of NICE guidance on sickle cell crises offers a very holistic approach to this medical emergency. In addition to the expected advice about clinical management, especially analgesia, the importance of “psychological and/or social support” is emphasised.
However, despite addressing the wide range of issues this challenging condition poses, NICE guidance appears to have neglected an important infectious cause of a “sickle cell crisis”. In particular, one should be mindful of the possibility of Parvovirus B19 infection, also known as “Slapped Cheek Disease” or erythema infectiosum.
This single-stranded DNA virus targets erythroid progenitor cells. Thus, in an acute sickle cell crisis, the clue is a low, or inappropriately low-normal reticulocyte count in the face of the typically profound anaemia of the sickle cell crisis.
Whilst “normal” children usually manifest the “slapped cheek appearance” which gives this condition its common name, adults will often have variable combinations of a non-specific erythematous rash, arthralgia, myalgia and flu-like symptoms.
Parvovirus B19 is a well-known precipitant of aplastic crises in patients with sickle cell disease patients (and patients with other haemoglobinopathies)[2,3,4]. This may seem like a small-print condition, but in fact the UK is currently experiencing a period of high Parvovirus B19 activity.
When patients with sickle cell disease and other hereditary haemoglobinopathies present with an acute aplastic crises e.g. a sickle cell crisis with no or a surprisingly low reticulocytosis, Parvovirus B19 infection should be considered. Appropriate serological investigations should be carried out.
If, in such a scenario, Parvovirus B19 infection is not suspected, there is a risk of nosocomial transmission of Parvovirus B19. This is an avoidable risk; as the famous microbiologist Louis Pasteur (1822-1895) once said: “fortune favours the prepared mind”.
1. Gillis VL et al. Management of an acute painful sickle cell episode in hospital: summary of NICE guidance. BMJ 2012;344 doi: 10.1136/bmj.e4063
2. Saarinen UM et al. Human Parvovirus B19-induced epidemic acute red cell aplasia in patients with hereditary hemolytic anemia. Blood 1986;67:1411-1417
3. Setubai S et al. Aplastic crisis caused by parvovirus B19 in an adult patient with sickle cell disease. Rev Soc Bras Med Trop 2000;33(5):477-481
4. Regaya F et al. Parvovirus b19 infection in Tunisian patients with sickle cell anemia and acute erythroblastopenia. BMC Infect Dis 2007;7:123 doi :10.1186/1471-2334-7-123
5. Health Protection Report HPA vol 6, No. 11. 16 June 2012 http://www.hpa.org.uk/Topics/InfectiousDiseases/InfectionsAZ/ParvovirusB19/ (link to pdf, accessed 24/7/12)
6. Bell LM et al. Human Parvovirus B19 infection amongst hospital staff members after contact with infected patients. NEJM 1989;321(8):485-91
Competing interests: No competing interests
This welcomed and timely NICE guidance has the potential to improve the care of sickle cell patients. It is disappointing the opportunity of advocating incentive spirometry as a effective simple and cheap (different brands available for as little as £14) non-pharmacological intervention was missed, given that up to 54% of patients currently receive it as standard care for their in-patient admission. It involves awake patients taking 10 maximal inspirations every two hours.
Randomised data in those presenting with chest or back pain demonstrates an absolute risk reduction of 36.8% (95% CI 12.5-61.2%) for pulmonary complications (associated with the development of acute chest syndrome), and reduced hospitalisations. Inclusion within this high-profile guideline would have improved suboptimal or inconsistent utilisation, and as the NNT is just 2.7 (95% CI 1.6-8.0) would have immediate benefit to both patients and budgets.
 Management of an acute painful sickle cell episode in hospital: summary of NICE guidance. Gillis VL, Senthinathan A, Dzingina M, Chamberlain K, Banks E, Baker MR, Longson D; on behalf of the Guideline Development Group. BMJ. 2012;344:e4063
 National Institute for Health and Clinical Excellence. Sickle cell acute painful episode: management of an acute painful episode in hospital. (Clinical guideline 143.) 2012. http://guidance.nice.org.uk/CG143.
 Miller ST, Kim HY, Weiner D, Wager CG, Gallagher D, Styles L, Dampier CD; Investigators of the Sickle Cell Disease Clinical Research Network (SCDCRN). Inpatient management of sickle cell pain: a 'snapshot' of current practice. Am J Hematol. 2012;87:333-6.
 Bellet PS, Kalinyak KA, Shukla R, Gelfand MJ, Rucknagel DL. Incentive spirometry to prevent acute pulmonary complications in sickle cell diseases. N Engl J Med. 1995;333:699-703.
Competing interests: No competing interests