72 Accid Emerg Med 1998;15:72-76 REVIEW The early management of meningococcal disease T J Hodgetts, A Brett, N Castle Neisseria meningitidis is an important cause of bacterial meningitis, particularly in infants over three months old and in teenagers. The relative importance of meningococcal disease over invasive Haemophilus influenzae disease has increased following the introduction of Hib capsular vaccines in 1990. In about one fifth of infections with Neisseria meningitidis the organ- ism causes a predominantly septicaemic illness.' Meningococcal meningitis and menin- gococcal septicaemia together constitute the spectrum of meningococcal disease. The over- all mortality of meningococcal disease is around 8% (up to 5% in meningitis, rising to 15-20% with septicaemia), which is improved by the early administration of antibiotics.'-3 The infection is characteristically fulminant, with rapid clinical deterioration and death in a matter of hours-the mortality is particularly high in meningococcal septicaemia when there has been a delay in diagnosis or treatment (up to 60% when there is septic shock3). Therefore early recognition and aggressive management will improve the outcome in meningococcal disease. Nationally there has been an increasing trend in laboratory confirmed meningococcal disease over the 10 years from 1985 to 1995 (Public Health Laboratory Service meningo- coccal reference laboratory, personal commu- nication; fig 1), although it is recognised that there is a consistent underreporting of survi- vors of meningococcal disease-perhaps be- cause of failure to confirm the diagnosis bacteriologically.' The importance of this infection at a community and district general hospital level has prompted the development of a treatment algorithm for prehospital and hos- pital use, to encourage the early aggressive treatment of this disease. In this paper we review the current recom- mendations for the early management of meningococcal disease, and present them as a comprehensive quick reference algorithm for ambulance personnel, general practitioners, accident and emergency clinicians, and paedia- tricians. Recognition It is important to recognise that there is a difference between meningococcal meningitis and meningococcal septicaemia, both in their presentation and management. These condi- tions are not, however, always clearly differen- tiated. The danger arises when both are collec- tively referred to as "meningococcal meningitis," with the subsequent failure to anticipate the development of septic shock, and the failure to direct treatment towards prevent- ing the progress of shock. Meningococcal meningitis characteristically manifests with fever, severe headache, vomit- ing, neck stiffness with positive Kernig's sign, photophobia, drowsiness, and confusion. In the very young the principal indicators will be fever, vomiting, drowsiness, poor feeding, and irritability.4 The characteristic feature of meningococcal septicaemia is a purpuric rash (fig 2) in a patient who is febrile and tachycardic. A purpuric rash in an unwell child should be treated as meningococcal septicaemia until proven otherwise. Signs of circulatory shock often develop rapidly with tachypnoea, tachy- cardia, cold peripheries, and oliguria. Drowsi- ness, and confusion in older children, are late signs. Limb pain (venous thrombosis or arthri- tis) may be a presenting feature. Prehospital management In all cases the priorities are to secure and maintain a clear airway, to give supplemental high concentration oxygen, and to support ventilation where needed. Rapid transport to hospital is essential. Parenteral benzylpenicillin given by the gen- eral practitioner is associated with a significant reduction in mortality from meningococcal disease.2 3 It is preferable to give this intrave- nously, but the intramuscular or intraosseous route are acceptable alternatives. The dose for meningococcal disease is 300 mg for infants, 600 mg for one to nine year olds, and 1200 mg for those of 10 years or more. There is no evi- dence to support the prehospital use of corticosteroids.3 In some circumstances the general practitioner may be involved in more extensive resuscitation, perhaps in rural areas when the prehospital time is prolonged and where the doctor has received extended practi- cal skills training on an advanced paediatric life support5 or paediatric advanced life support6 course. In this case the intraosseous route should be considered when intravenous access is difficult and fluid is required in addition to the antibiotics. Accident and emergency management The immediate management is again directed towards the support of the airway, breathing, Accident and Emergency Department, Frimley Park Hospital NHS Trust, Portsmouth Road, Camberley, Surrey GU16 5UJ, UK T J Hodgetts A Brett N Castle Correspondence to: Major T J Hodgetts. email: tim@blenheim. softnet.co.uk Accepted for publication 21 July 1997 72 on August 1, 2020 by guest. Protected by copyright. http://emj.bmj.com/ J Accid Emerg Med: first published as 10.1136/emj.15.2.72 on 1 March 1998. Downloaded from
Transcript
72 Accid Emerg Med 1998;15:72-76
REVIEW
The early management of meningococcal disease
T J Hodgetts, A Brett, N Castle
Neisseria meningitidis is an important cause ofbacterial meningitis, particularly in infantsover three months old and in teenagers. Therelative importance of meningococcal diseaseover invasive Haemophilus influenzae diseasehas increased following the introduction ofHibcapsular vaccines in 1990. In about one fifth ofinfections with Neisseria meningitidis the organ-ism causes a predominantly septicaemicillness.' Meningococcal meningitis and menin-gococcal septicaemia together constitute thespectrum of meningococcal disease. The over-all mortality of meningococcal disease isaround 8% (up to 5% in meningitis, rising to15-20% with septicaemia), which is improvedby the early administration of antibiotics.'-3The infection is characteristically fulminant,with rapid clinical deterioration and death in amatter of hours-the mortality is particularlyhigh in meningococcal septicaemia when therehas been a delay in diagnosis or treatment (upto 60% when there is septic shock3). Thereforeearly recognition and aggressive managementwill improve the outcome in meningococcaldisease.
Nationally there has been an increasingtrend in laboratory confirmed meningococcaldisease over the 10 years from 1985 to 1995(Public Health Laboratory Service meningo-coccal reference laboratory, personal commu-nication; fig 1), although it is recognised thatthere is a consistent underreporting of survi-vors of meningococcal disease-perhaps be-cause of failure to confirm the diagnosisbacteriologically.' The importance of thisinfection at a community and district generalhospital level has prompted the development ofa treatment algorithm for prehospital and hos-pital use, to encourage the early aggressivetreatment of this disease.
In this paper we review the current recom-mendations for the early management ofmeningococcal disease, and present them as acomprehensive quick reference algorithm forambulance personnel, general practitioners,accident and emergency clinicians, and paedia-tricians.
RecognitionIt is important to recognise that there is adifference between meningococcal meningitisand meningococcal septicaemia, both in theirpresentation and management. These condi-tions are not, however, always clearly differen-tiated. The danger arises when both are collec-
tively referred to as "meningococcalmeningitis," with the subsequent failure toanticipate the development of septic shock, andthe failure to direct treatment towards prevent-ing the progress of shock.Meningococcal meningitis characteristically
manifests with fever, severe headache, vomit-ing, neck stiffness with positive Kernig's sign,photophobia, drowsiness, and confusion. Inthe very young the principal indicators will befever, vomiting, drowsiness, poor feeding, andirritability.4The characteristic feature of meningococcal
septicaemia is a purpuric rash (fig 2) in apatient who is febrile and tachycardic. Apurpuric rash in an unwell child should betreated as meningococcal septicaemia untilproven otherwise. Signs of circulatory shockoften develop rapidly with tachypnoea, tachy-cardia, cold peripheries, and oliguria. Drowsi-ness, and confusion in older children, are latesigns. Limb pain (venous thrombosis or arthri-tis) may be a presenting feature.
Prehospital managementIn all cases the priorities are to secure andmaintain a clear airway, to give supplementalhigh concentration oxygen, and to supportventilation where needed. Rapid transport tohospital is essential.
Parenteral benzylpenicillin given by the gen-eral practitioner is associated with a significantreduction in mortality from meningococcaldisease.2 3 It is preferable to give this intrave-nously, but the intramuscular or intraosseousroute are acceptable alternatives. The dose formeningococcal disease is 300 mg for infants,600 mg for one to nine year olds, and 1200 mgfor those of 10 years or more. There is no evi-dence to support the prehospital use ofcorticosteroids.3 In some circumstances thegeneral practitioner may be involved in moreextensive resuscitation, perhaps in rural areaswhen the prehospital time is prolonged andwhere the doctor has received extended practi-cal skills training on an advanced paediatric lifesupport5 or paediatric advanced life support6course. In this case the intraosseous routeshould be considered when intravenous accessis difficult and fluid is required in addition tothe antibiotics.
Accident and emergency managementThe immediate management is again directedtowards the support of the airway, breathing,
Figure 1 Laboratory confirmed meningococcal disease inEngland and Wales, 1984-1995. (Source: Public HealthLaboratory Service reference laboratory.)
and circulation.5 Cardiorespiratory failure is a
common feature of meningococcal septicaemicshock; high concentrations of oxygen should begiven to all patients, and early ventilation,initially with 100% oxygen, is often required.Do not wait for respiratory failure to developwhen you are treating septicaemic shock: acutelung injury is common, and early elective ven-
tilation is indicated.Vomiting should be anticipated and consid-
eration given to electively intubating and venti-lating any patient with a reduced level ofresponse, in order to protect the airway. Anintragastric tube should otherwise be placedearly in the spontaneously breathing patient.Hypovolaemia is consistently present in
meningococcal septicaemia, as a result of thewidespread increase in vascular permeability.Repeated boluses of fluid are needed to restorethe peripheral circulation. Colloid is preferredbecause the fluid lost is protein rich, and 4.5%human albumin solution is preferred to thesynthetic colloids. Fluid is given in 20 ml/kgboluses, the weight of the child being estimatedin one of the following ways: (1) asking a
parent; (2) by relating it to the child's length ona Broselow tape or paediatric resuscitationchart7; (3) by using the formula weight (kg) =
[age in years + 4] x 2, which is accurate fromone to 10 years.
In the septicaemic child who requires imme-diate fluid resuscitation there should be no
delay in inserting an intraosseous needle if twoattempts at peripheral venous cannulation fail,or more than 90 seconds elapse.5 Fluids anddrugs are then best given by syringe and a shortconnection tube (the connection tube preventsrepeated direct pressure on the needle). It iswise to protect this line, for example in a boxsplint. The intraosseous route is generally rec-
ommended for children aged six years or less.Cold extremities, a delayed capillary refill
time, a rising pulse and respiratory rate, confu-sion, and a poor urine output are all indicatorsof developing septic shock and inadequateresuscitation of the circulation. Hypotension isa late sign in children, and when it occurs it isoften precipitous.The traditional antibiotic of choice for Neis-
seria meningitidis is benzylpenicillin. Penicillinresistant meningococci have been recognisedin Spain and South Africa, and a small numberof penicillin resistant isolates have been identi-fied in the United Kingdom.8 For this reason,
and because other pathogens may commonlyproduce a meningitis picture (and on occasiona septicaemic picture), a broad spectrum thirdgeneration cephalosporin is recommended asfirst line antimicrobial treatment. Additionalpenicillin is not required.4 Either cefo-taxime 200 mg/kg/day in three or four divideddoses, or ceftriaxone 80 mg/kg/day in a singledaily dose (as it has a much longer half life) aresuitable.4 The single daily dose of ceftriaxoneis attractive, but it is associated with a higherincidence of diarrhoea. It has also been recom-mended that the first dose of antibiotics isincreased by 50%, to ensure a high initialserum and CSF concentration.'2For meningitis and septicaemia in infants
one to three months old additional ampicillin200 mg/kg/day is recommended,8 113 to ensureactivity against an increased pathogenic spec-trum which includes Escherichia coli, Listeriamonocytogenes, and salmonella species.'014Hypoglycaemia is common in any child who
is seriously unwell, and must be anticipated inthe septicaemic child. Capillary blood glucoseestimates should be performed regularly, andhypoglycaemia corrected when values fallbelow 2.0 mmol/litre. A range of electrolytedisturbances can also occur (hypocalcaemia,hypokalaemia, hypomagnesaemia, hypophos-phataemia) and these should be tested for andcorrected where appropriate. Blood shouldalso be taken for a clotting screen and crossmatch, and blood gas analysis can be used asan adjunct to monitor the effectiveness ofresuscitation. Overt coagulopathy may beidentified by bleeding from venepuncture sites,necessitating fresh frozen plasma. Anaemia canbe profound and blood may be required afterthe initial colloid resuscitation.The evidence for the benefit of dexametha-
sone in the management of meningitis is farfrom conclusive, although the drug has been inregular use for several years.'0 15 The currentrecommendation of the infectious diseasescommittee of the American Academy ofPediatrics is to use dexamethasone (0.15mg/kg six hourly'4) for the treatment of menin-gitis caused by H influenzae, and simply toconsider its use for meningitis of unknown ori-gin, or known to be caused byN meningitidis orS pneumoniae.'6 Accident and emergency clini-cians should seek the advice of medical stafffrom the admitting paediatric intensive careunit with respect to the use of steroids.
Confirming the diagnosisThe diagnosis is largely a clinical one. Onarrival in hospital venous blood should betaken for blood cultures, but the yield will bereduced by the benzylpenicillin given by thegeneral practitioner. Lumbar puncture shouldbe considered in patients with meningitis, butnot those with septicaemia (because it will notalter clinical management, and the cerebrospi-nal fluid (CSF) is likely to be sterile) orevidence of raised intracranial pressure (be-cause it may produce cerebral herniation)."The diagnosis may also be confirmed byculture from a throat swab or rash aspirate,antigen detection, serodiagnosis, and polymer-
Figure 2 Purpuric rash of meningococcal septicaemia.
ase chain reaction testing of blood or CSF,3which will not be affected by the administra-tion of antibiotics.There is no role for computerised tomogra-
phy in the initial management of patients withlife threatening meningococcal disease.
Definitive careThe further management of patients sufferingfrom meningococcal disease must address themultisystem nature of the illness. Patients withmeningitis and no depression of consciouslevel may be managed on a general ward. How-ever, they must be assessed repeatedly, as dete-rioration may be sudden and catastrophic.Indications for elective intubation and ventila-tion are potential airway compromise, severe
agitation, recurrent or refractory seizures, andimpending or established respiratory failure.
Children who have been intubated, whohave shock or evidence of disseminated intra-vascular coagulopathy (including rapidly pro-gressive purpuric rash), or who have metabolicacidosis should be referred to a specialistpaediatric intensive care unit (PICU). Adultsrequiring continuing respiratory or cardiovas-cular support are managed on a general inten-sive care unit. Prognostic indicators andscoring systems have been used to predict dis-ease progression, and the requirement for spe-cialist care, based on clinical and laboratoryinformation.4 '7There are 15 paediatric intensive care
retrieval teams in the United Kingdom (tel-ephone survey of all PICUs listed in the 1996Directory of emergency and special care units'8)and early contact by the referring district gen-eral hospital is to be recommended where thisservice is available.Those children with meningococcal septi-
caemia and haemodynamic instability shouldat first receive aggressive fluid resuscitation.Hypotension is the result of hypovolaemia,dysregulation of vascular tone, and myocardialdysfunction-inotropic support is very oftenrequired. Dobutamine, low dose dopamine,and adrenaline are used, but practice variesthroughout the country. An initial combinationof dobutamine and low dose dopamine are rec-
ommended when 40 ml/kg of colloid has beengiven. Insertion of a central venous pressureline will provide vital information concerningvolume status.The acute respiratory distress syndrome and
multiple organ dysfunction syndrome are welldescribed complications of meningococcalsepticaemia, and advanced treatment strategieshave included extracorporeal membrane oxy-genation, high frequency jet ventilation, andnitric oxide, with variable degrees of success inboth children'9 20 and adults.2'
The algorithmThe algorithm is presented as a double sidedA4 sheet for rapid reference (fig 3), and isdivided into three sections: recognition, imme-diate actions, and specific treatment. It isintended to be used by ambulance staff,general practitioners, accident and emergencyclinicians, and paediatricians in the early man-agement of meningitis and meningococcal sep-ticaemia. The principal objective is to deliveran appropriately resuscitated patient to thedefinitive care facility (ward or intensive careunit). The algorithm does not attempt todictate the policy of a specialist intensive careunit.
RECOGNITIONMeningitis is recognised by the history andexamination (as described above). The under-lying causative organism is not importantinitially, as all cases of meningitis should betreated in the same manner. Meningococcalsepticaemia will be suspected in a febrile childwho is shocked and who has a petechial rash.
IMMEDIATE ACTIONSThe objectives of the ambulance service are:* To maintain and secure a clear airway;* To provide supplemental high concentration
oxygen, and to assist ventilation if needed;* To provide rapid transport to hospital;* To warn the accident and emergency
department in advance.The need for antibiotic prophylaxis for theambulance crew is a common concern: it is notrequired unless mouth to mouth ventilationhas been given.
The general practitioner has an important roleto give benzylpenicillin:* Intravenous, intraosseous, or intramuscular
benzylpenicillin, 300 mg < 1 year, 600 mgone to nine years, 1200 mg > 10 years.
The accident and emergency department shouldassemble a resuscitation team, to include anexperienced anaesthetist and paediatrician,and follow these steps:* Give supplemental high concentration oxy-
gen, and consider intubation and ventila-tion;
* Obtain blood cultures (and other venoussamples) when intravenous access is estab-lished;
* Expand blood volume with colloid, ideally4.5% human albumin solution, as a 20ml/kg bolus; reassess the effect on the circu-lation and repeat the bolus as required;
* Check capillary blood glucose repeatedly,and treat hypoglycaemia with intravenousdextrose when this is < 2.0 mmol/litre.
SPECIFIC TREATMENTThe algorithm provides a table of drug dosesfor cefotaxime and ceftriaxone up to 40 kgbody weight. Maximum daily doses of thesedrugs are listed. Doses for patients weighingmore than 40 kg, or for weights between theincrements of 10 kg, are calculated by a simplesum. For example, the 16 kg dose is calculatedby adding the 10 kg dose to the 6 kg dose. Thefirst dose of cefotaxime has been calculated tobe 50% greater than the maintenance dose'3 toensure high initial CSF and serum concentra-tions; a similar increase for the first dose ofceftriaxone is not currently recommended bythe manufacturers. The algorithm also lists theprecalculated fluid and 10% dextrose boluses.Inotropes should be considered if the circula-tion does not adequately respond to 40 ml/kgof colloid: the standard doses of dobutamineand dopamine are listed.
ConclusionMeningococcal disease is a life threateningillness, although relatively uncommon, whichparticularly affects children and adolescents.As an individual doctor's experience in themanagement of this disease is likely to be lim-ited, involvement in such a paediatric resusci-tation will be stressful. However, early andaggressive treatment by the general prac-titioner, accident and emergency clinician, andthe paediatrician may improve outcome.
It is for this reason that the meningitis andmeningococcal septicaemia algorithm has beendevised, to remind the doctor of the simpleimportant resuscitation steps and to provide arapid reference for key drug doses and fluidsgiven in the resuscitation.
Copies of the algorithm are available fromHoechst Marion Roussel (phone 0800282833), or by sending a stamped addressedenvelope (marked "Meningitis algorithm" inthe bottom left hand corner) to the NationalMeningitis Trust, Fern House, Bath Road,Stroud GL5 3TJ, UK.
SummaryMeningococcal disease is a fulminant infectionwith an overall mortality of 8%. Mortality issignificantly increased with meningococcalsepticaemia, particularly when there has been adelay in the diagnosis. The trend from 1985 to1995 has been an increase in incidence of thisdisease, and the relative importance of menin-
gococcal disease has also increased following afall in the incidence of invasive Haemophilusinfluenzae disease with childhood immunisa-tion. The management of such cases can becomplex and time critical. Patients withmeningococcal septicaemia often require ag-gressive resuscitation, including airway sup-port, intravenous colloid, and parenteral anti-biotics; hypoglycaemia is also commonly seen,and inotropes may be needed to support thecirculation.We examine the treatment strategies in the
early management of meningococcal diseaseand provide an algorithm for use by ambulancepersonnel, general practitioners, accident andemergency clinicians, and paediatricians. Theobjective of this algorithm is to ensure that anoptimally resuscitated patient is delivered tothe definitive care facility.
The sponsors of the algorithm are also the manufacturers ofcefotaxime. The algorithm has been produced as a service tomedicine without any material gain to the authors. No conflictof interest is declared.
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