Rapid Responses to:
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Rapid Responses: Rapid Responses published:
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Don't forget about cerebral perfusion.
- Peter J Flegg (16 June 2008)
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Fundoscopy in meningococcal disease
- Roger H Armour (17 June 2008)
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Antibiotic use
- David Mitchell (18 June 2008)
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Near-patient testing of respiratory specimens
- Derek J. Fairley, Kathy Dunlop, James McKenna, Paul Jackson, Michael Shields, Peter V. Coyle. (24 June 2008)
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Detecting meningitis: a need for better information in primary care
- Minu Philipose, David Crook and Helen Smith (16 September 2008)
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NEJM CORTICUS 2008 study on corticosteroids in septic shock
- Nishith K Singh (17 October 2009)
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Peter J Flegg, Consultant Physician Blackpool Victoria Hospital, FY3 8NR
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I am somewhat surprised that the SIGN guidelines (and therefore this summary of them) make no mention of the importance of adequate cerebral perfusion in those with invasive meningococcal disease. Cerebral perfusion pressure is the difference between the mean arterial pressure (which is usually low from the associated hypotensive shock) and the intracranial pressure (ICP, which is often high as a result of meningeal inflammation and cerebral oedema). CPP = MAP-ICP Consequently, cerebral perfusion pressure takes a "double whammy", and the end result may be significant cerebral ischaemia from profoundly inadequate cerebral perfusion, which is likely to worsen neurological outcomes. The SIGN guidelines discuss the importance of early inotropic support, but fail to address the issues of raised ICP and the reduction in cerebral perfusion. If there are clinical or CT scan signs of raised ICP, the use of osmotic agents such as mannitol should be actively considered and if necessary repeated. Children and adults with severe invasive meningococcal disease often end up on the intensive care unit where they may be sedated and ventilated while their cardiorespiratory status is optimised. In these circumstances it is difficult to detect whether there have been any neurological changes or a drop in conscious level consequent to a raised ICP. A normal brain scan may not exclude this, and it may be difficult to detect. Surrogate methods of detecting poor cerebral perfusion such as jugular venous bulb oxygen saturation and the use of ICP monitoring may need to be considered. Competing interests: None declared |
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Roger H Armour, Honorary Consultant Surgeon (retired consultant surgeon) Lister Hospital Stevenage SG1 4AB
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Neither Theilen et al (1) nor Isaacs (2) mention examination of the ocular fundus in their recommendations for the management of these seriously ill patients. Did they routinely examine the ocular fundi, and if so what were their findings? In 1994 Sheila Crispin, a veterinary ophthalmologist wrote, "...examination of the fundus should always be included as part of the clinical examination of the sick cat...[the] findings although not necessarily pathognomonic of a specific disease may well indicate systemic disease"[3]. Are our veterinary colleagues ahead of us? There is an ever-growing gap between ophthalmology and other specialties, but it should not be difficult for us non-specialists to recognise retinal haemorhages or cotton wool spots. In the case of meningococcal septicaemia perhaps they precede the cutaneous petechiae? References 1) Theilen U, Wilson L, Wilson G, Beattie JO, Qureshi S, Simpson D, Management of invasive meningococcal disease in children and young people: a summary of SIGN guidelines. BMJ 2008;336:1367-1370 2) Isaacs D. Commentary on 1). BMJ 2008;336:1370-1371 3) Crispin SM, in Barnett KC, Crispin SM. Feline ophthalmology: and atlas and text. London: Saunders 1994, 147 Competing interests: I am a director and small shareholder of Ophthalmos Ltd that makes a lensfree ophthalmoscope. |
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David Mitchell, Microbiologist Trinity College
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Dear Sir/Madam I confess to being a little confused by the recommendations given here. The paper recommends cefotaxime (or ceftiaxone) for meningococcal disease. Thankfully this organism remains sensitive to agents with narrower spectra of activity so the case for a third generation cephlosporin is (in my opinion) difficult to justify. Curiously the authors mention the introduction of ampicillin or amoxacillin in particularly young children in case the diagnosis is listeriosis. Since the topic addressed in this article is meningococcal disease, this inclusion looks somewhat out of place. Secondly meningococci are sensitive to amoxacillin or ampicillin so why one would use a cephlosporin at all here is not clear. A serious omission I see with the paper is the failure to address the case of a child who cannot be given any beta lactams because of allergy. My (possibly mistaken) impression of these guidelines is that the authors were concerned that the final diagnosis might not be meningococcal disease and wished to ensure that other agents that may mimic this dread disease were also treated. This is (in my opinion) a very reasonable approach to take initially but once the diagnosis is confirmed by microscopy, culture and/or PCR I would question the recommendation here to use a third generation cephlosporin both on the basis of cost and for control of antibiotic resistance. This last point is particularly important in the intensive care unit where many of the most resistant organisms can be found. I would be surprised if these points were not raised during peer review of this article. Competing interests: None declared |
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Derek J. Fairley, Research Scientist Belfast Health & Social Care Trust, Royal Hospitals, Grosvenor Road, Belfast, BT12 6BA, Kathy Dunlop, James McKenna, Paul Jackson, Michael Shields, Peter V. Coyle.
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The SIGN guidelines (1) and commentary by Isaacs (2) highlight early diagnosis and referral for improving clinical outcomes in meningococcal disease (MD). They also highlight management difficulties when children present without ‘classical’ symptoms and early treatment options are missed. The SIGN guidelines recommend a formal reassessment within 6 hours, implying the use of clinical deterioration as a diagnostic indicator. Current HPA guidelines (3) advise on the use of several specimens, including respiratory secretions, as part of a diagnostic algorithm for confirming invasive MD. Unfortunately no laboratory tests, whether culture or molecular based, are useful in the initial diagnosis of MD (3). We believe that in children this represents a missed opportunity for initiating early treatment that needs to be reassessed. Our data suggest that a rapid molecular test for meningococci in throat and nasal swabs would be useful in the diagnosis of MD in young children, with or without classical symptoms. To be most effective this would need to be delivered as a point-of-care test. Previously we have shown (4) that in most cases of MD there is no evidence to link respiratory virus infection with presentation and that the prodromal flu-like symptoms were caused by meningococcal replication. Of 104 suspected MD cases (median age 2.2 years; range 0.04 to 15.2) direct molecular detection of meningococci in respiratory specimens was feasible, with PCR detection of the ctrA and porA genes being strongly associated with a subsequent diagnosis of MD (PPV 100%, 17/17; NPV 92%, 44/48; sensitivity 81%, 17/21; specificity 100%, 44/44). We have also confirmed (using porA gene sequencing) that the meningococcal strains identified in blood and respiratory secretions in these children were identical. Conversely the asymptomatic carriage rate of meningococci, detected by PCR testing of nasopharyngeal swabs, was very low (2.2%). This suggests that the small risk of treating carriage in young children is heavily outweighed by the diagnostic value of early molecular detection of meningococci in respiratory swab specimens. We are currently addressing the problem of applying suitable molecular tests with rapid turnaround times in near-patient settings. While we support the SIGN advice to clinically reassess after 6 hours, identifying meningococci in a child’s nasopharynx at initial assessment could eliminate this delay. A negative result would not exclude the diagnosis, but a positive one would allow early referral and treatment. Development of effective near-patient test formats and critical assessment of whether molecular detection of capsular meningococci in respiratory specimens is a useful diagnostic indicator should be the focus of further research. References. 1. Theilen U, Wilson L, Wilson G, Beattie JO, Qureshi S, Simpson D. Management of invasive meningococcal disease in children and young people: summary of SIGN guidelines. BMJ 2008;336:1367-70. 2. Isaacs D. Commentary: Controversies in SIGN guidance on management of invasive meningococcal disease in children and young people. BMJ 2008;336:1370-1. 3. Health Protection Agency Meningococcus Forum. Guidance for public health management of meningococcal disease in the UK, 2006. Health Protection Agency UK. http://www.hpa.org.uk/web/HPAwebFile/HPAweb_C/1194947389261 4. Dunlop KA, Coyle PV, Jackson P, Patterson CC, Shields MD. Respiratory viruses do not trigger meningococcal disease in children. J Infect. 2007;54:454-8. Competing interests: We have been funded by the Meningitis Research Foundation to develop a rapid molecular test for detection of meningococcus in clinical specimens. |
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Minu Philipose, Trainee in Obstetrics and Gynaecology Lagan Valley Hospital, Belfast BT28 1JP, David Crook and Helen Smith
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The new SIGN Guidelines [1] on invasive meningococcal disease in children and young people emphasize the life-critical nature of the first 24 hours following presentation. These authors' appraisal of the literature on primary care assessment of this disease reveals substantial weaknesses in the quality of the evidence-base. This finding would support the conclusion of the related NICE Guidelines [2] that many GPs are unsure of the referral threshold for a febrile child. We have for some time been concerned over the quality of the diagnostic resources available to the GP faced with such a child. We appraised a series of 20 medical textbooks and journal articles that are commonly accessed by our local GPs. We wanted to see how well they covered the six topics we consider to be key to the diagnosis of meningitis in the febrile child: • symptoms • physical examination • vital signs • normal parameters for vital signs • assessment of the level of consciousness • criteria for referral for paediatric assessment Most topics were addressed to some degree in our survey, but the standard of information was heterogenous and it is a concern that no single source of information covered all six topics. Prompt identification of meningitis in the young is likely to save lives, but we are concerned that this is being hindered by the absence of a robust protocol for primary care. 1. Theilen U, Wilson L, Wilson G, Beattie JO, Qureshi S, Simpson D on behalf of the Guideline Development Group. Management of invasive meningococcal disease in children and young people: summary of SIGN guidelines. BMJ 2008; 336: 1367-1370. 2. National Institute for Health and Clinical Excellence. Feverish illness: assessment and initial management in children younger than 5 years. London: NICE; 2007. Competing interests: None declared |
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Nishith K Singh, Resident physician Southern Illinois University School of Medicine, IL US 62704
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This is regards the CORTICUS analysis published by Sprung et al (1) in New England Journal of Medicine and which has been cited by the current BMJ article. I would draw reader's attention to a simple yet crucial analysis which can be attempted between the NEJM's CORTICUS study and the previous similar JAMA paper by Annane et al in 2002. (2) Before I started this analysis, I assumed that an adrenal insufficient state is defined biochemically using serum cortisol levels and by seeing the response to corticotropin (exactly similar to the one used by the investigators being discussed here). I found that the steroids recieving patients in CORTICUS had mean basal cortisol levels (30+-20 microgram/dl, n=125) and 60 minute levels(33+-19 microgram/dl, n=125) much higher(p values 0.0001 and 0.0001 respectively) than in the corresponding group (basal = 18+-12 microgram/dl, and 60 min levels and 20+-12microgram/dl, n=114) of Dr Annane's previous paper.(2) I also found that response to corticotropin in Hydrocortisone group of "non-responders" in the present study was lower(p=0.031) than in the previous study although the corresponding placebo groups had similar corticotropin response(p=0.237).This may be a significant way to explain the difference in mortality benefits seen between the studies and a more severe relative adrenal insufficiency may be used as a measure of risk stratification to differentiate patients who may benefit from steroids and who will not. It was interesting to note that 28 day mortality difference in the hydrocortisone group and the placebo group between the responders and non-responders was non-significant(p value = 0.1 and 0.27 respectively). Similar analysis on the previous study by Annane also reveals insignificant difference between responders and non-responders. So this questions the widely used belief that an adrenal insufficient state confers mortality disadvantage in the first place. To summarise, a severely depleted(adrenally) septic shock patient may still be given steroids to achieve a small benefit in mortality(may be better than the treated group in responders) and that they have similar mortality rates to responders if untreated. The reason for this finding and the cut-off levels to define the very severe state are yet to be determined. References; 1.Sprung CL, Annane D, Keh D, Moreno R, Singer M, Freivogel K, Weiss YG, Benbenishty J, Kalenka A, Forst H, Laterre PF, Reinhart K, Cuthbertson BH, Payen D, Briegel J; CORTICUS Study Group.Hydrocortisone therapy for patients with septic shock.N Engl J Med. 2008; 358(2):111-24. 2.Annane D, Sebille V, Charpentier C, et al. Effect of treatment with low doses of hydrocortisone and fludrocortisone on mortality in patients with septic shock. JAMA. 2002;288:862-871. Competing interests: None declared |
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