Recommendations
Urgent
Think 'Could this be sepsis?' based on acute deterioration in a patient in whom there is clinical evidence or strong suspicion of infection.[26][37][38]
Use a systematic approach, alongside your clinical judgement, for assessment; urgently consult a senior clinical decision-maker (e.g., ST4 level doctor in the UK) if you suspect sepsis.[37][38][39][40]
Refer to local guidelines for the recommended approach at your institution for assessment and management of the patient with suspected sepsis.
Meningococcal disease (systemic meningococcal sepsis with or without meningococcal meningitis) is covered in our topic Meningococcal disease.
Urgent: in hospital
Manage cardiorespiratory arrest, sepsis, meningococcal disease (not covered here), and shock.[16]
These problems take priority over ‘uncomplicated’ bacterial meningitis.
Follow your local protocol.
See Meningococcal disease, Sepsis in adults, and Shock.
Perform all the following for patients with presumed uncomplicated bacterial meningitis within 1 hour of presentation to hospital.[16]
Seek advice from a senior clinical decision-maker.[16]
Refer to critical care and delay lumbar puncture if the patient has:[16]
Respiratory compromise
Signs of raised intracranial pressure
Frequent seizures
Altered mental state (Glasgow Coma Scale [GCS] ≤12 or a drop of >2 points) [ Glasgow Coma Scale Opens in new window ]
Signs of sepsis
Rapidly evolving rash.
Secure the airway.[16]
Monitor controlled oxygen therapy. An upper SpO2 limit of 96% is reasonable when administering supplemental oxygen to most patients with acute illness who are not at risk of hypercapnia. A lower target of 88% to 92% is appropriate if the patient is at risk of hypercapnic respiratory failure.[73]
Strongly consider intubating if GCS <12.[16] [ Glasgow Coma Scale Opens in new window ]
Give intravenous dexamethasone:[16]
Ideally shortly before or simultaneously with antibiotics.
Give empirical intravenous antibiotics immediately after blood cultures.[16]
Taking blood for culture should not delay administration of antibiotics.[16]
Do not delay starting antibiotics for lumbar puncture (LP). The need for a rapid LP has to be weighed against the desire to start antimicrobial treatment urgently.[16]
Some guidelines recommend giving antibiotics after LP (where LP is indicated and as long as LP is not delayed) to allow the best chance of definitive diagnosis.[16] The culture rate can drop off rapidly after 4 hours, making it difficult to identify the causative organism (but prompt molecular tests will still identify the causative organism even after antibiotics have been started).
If LP cannot be performed within 1 hour, give antibiotics immediately after blood cultures have been taken.[16]
Empirical antibiotics are determined by the epidemiology of the causative organisms and specific patient age groups.[25]
Seek advice from a microbiologist and follow your local protocol.
Seek specialist advice for patients with suspected tuberculous meningitis.
Current information on antimicrobial resistance is available:
Give fluids to maintain normal haemodynamic parameters.[16][74]
Urgent: in the community
Refer all patients with suspected meningitis and/or meningococcal sepsis to hospital immediately (usually by blue-light ambulance in the UK).[16]
Give patients with suspected meningitis empirical intravenous or intramuscular antibiotics prior to hospital transfer if there will be a delay of more than 1 hour in getting them to hospital.[16] Follow your local protocol.
Key Recommendations
Raised intracranial pressure
Do not routinely monitor intracranial pressure (ICP).[16]
Perform basic measures to control ICP in patients with suspected or confirmed raised ICP.
Seizures
Treat suspected or confirmed seizures early with anticonvulsants and monitor patients with suspected or confirmed status epilepticus with EEG.[16]
Infection control
Ensure respiratory isolation for all patients with suspected meningitis until they have received 24 hours of intravenous antibiotics.[16]
Apply droplet precautions until the patient has had 24 hours of effective antibiotic treatment, including:[16][75]
Single-room nursing
Surgical masks
Standard infection prevention precautions.
Fluids
Do not restrict fluids to reduce cerebral oedema.[16]
Manage cardiorespiratory arrest, sepsis, meningococcal disease, and shock.[16] These take priority over ‘uncomplicated’ bacterial meningitis. Follow your local protocols.
This topic covers only patients with meningitis that is not complicated by suspected sepsis.
See Sepsis in adults, Shock, and Meningococcal disease.
Seek advice from a senior clinical decision-maker within the first hour after presentation to hospital.[16]
Practical tip
Think 'Could this be sepsis?' based on acute deterioration in a patient in whom there is clinical evidence or strong suspicion of infection.[26][37][38]
The patient may present with non-specific or non-localised symptoms (e.g., acutely unwell with a normal temperature) or there may be severe signs with evidence of multi-organ dysfunction and shock.[26][37][38]
Remember that sepsis represents the severe, life-threatening end of infection.[76]
Meningococcal disease (systemic meningococcal sepsis with or without meningococcal meningitis) is covered in our separate topic Meningococcal disease.
Use a systematic approach (e.g., National Early Warning Score 2 [NEWS2]), alongside your clinical judgement, to assess the risk of deterioration due to sepsis.[26][37][39][77] Consult local guidelines for the recommended approach at your institution.
If you suspect sepsis in a patient with meningitis, arrange urgent review within 30 minutes by a senior clinical decision-maker (e.g., ST4 level doctor in the UK).[40]
Follow your local protocol for investigation and treatment of all patients with suspected sepsis, or those at risk. Start treatment promptly. Determine urgency of treatment according to likelihood of infection and severity of illness, or according to your local protocol.[40][77]
See Sepsis in adults.
Involve the intensive care team and delay lumbar puncture if patients have:[16]
Respiratory compromise
Signs of raised intracranial pressure
Frequent seizures
Altered mental state (Glasgow Coma Scale [GCS] score ≤12 or a drop of >2 points) [ Glasgow Coma Scale Opens in new window ]
Signs of sepsis
Rapidly evolving rash.
Strongly consider intubation if GCS score is <12.[16] [ Glasgow Coma Scale Opens in new window ]
How to use bag-valve-mask apparatus to deliver ventilatory support to adults. Video demonstrates the two-person technique.
How to insert a tracheal tube in an adult using a laryngoscope.
Specific GCS levels indicating a need to delay lumbar puncture or to obtain cranial imaging are debated. Seek senior advice if you are uncertain about either of these situations.
Raised intracranial pressure
Seek critical care input if the patient has signs of raised intracranial pressure.[16]
Several measures may be helpful when attempting to reduce intracranial pressure, but there is little evidence for any of these options:[16][81]
Do not routinely monitor intracranial pressure (outside of critical care).[16]
Consider intubation if Glasgow Coma Scale score <12.[16]
Indications for intubation |
|
How to use bag-valve-mask apparatus to deliver ventilatory support to adults. Video demonstrates the two-person technique.
How to insert a tracheal tube in an adult using a laryngoscope.
Monitor controlled oxygen therapy. An upper SpO2 limit of 96% is reasonable when administering supplemental oxygen to most patients with acute illness who are not at risk of hypercapnia.
Evidence suggests that liberal use of supplemental oxygen (target SpO2 >96%) in acutely ill adults is associated with higher mortality than more conservative oxygen therapy.[84]
A lower target SpO2 of 88% to 92% is appropriate if the patient is at risk of hypercapnic respiratory failure.[73]
Evidence: Target oxygen saturation in acutely ill adults
Too much supplemental oxygen increases mortality.
Evidence from a large systematic review and meta-analysis supports conservative/controlled oxygen therapy versus liberal oxygen therapy in acutely ill adults who are not at risk of hypercapnia.
Guidelines differ in their recommendations on target oxygen saturation in acutely unwell adults who are receiving supplemental oxygen.
The 2017 British Thoracic Society (BTS) guideline recommends a target SpO2 range of 94% to 98% for patients not at risk of hypercapnia, whereas the 2022 Thoracic Society of Australia and New Zealand (TSANZ) guideline recommends 92% to 96%.[73][85]
The Global Initiative For Asthma (GINA) guidelines recommend a target SpO2 range of 93% to 96% in the context of a severe exacerbation of asthma.[86]
A systematic review including a meta-analysis of data from 25 randomised controlled trials published in 2018 found that in adults with acute illness, liberal oxygen therapy (broadly equivalent to a target saturation >96%) is associated with higher mortality than conservative oxygen therapy (broadly equivalent to a target saturation ≤96%).[84] In-hospital mortality was 11 per 1000 higher for the liberal oxygen therapy group versus the conservative therapy group (95% CI 2 to 22 per 1000 more). Mortality at 30 days was also higher in the group who had received liberal oxygen (relative risk 1.14, 95% CI 1.01 to 1.29). The trials included adults with sepsis, critical illness, stroke, trauma, myocardial infarction, or cardiac arrest, and patients who had emergency surgery. Studies that were limited to people with chronic respiratory illness or psychiatric illness, or patients on extracorporeal life support, receiving hyperbaric oxygen therapy, or having elective surgery, were all excluded from the review.
An upper SpO2 limit of 96% is therefore reasonable when administering supplemental oxygen to patients with acute illness who are not at risk of hypercapnia. However, a higher target may be appropriate for some specific conditions (e.g., pneumothorax, carbon monoxide poisoning, cluster headache, or sickle cell crisis).[87]
In 2019 the BTS reviewed its guidance in response to this systematic review and meta-analysis and decided an interim update was not required.[88]
The committee noted that the systematic review supported the use of controlled oxygen therapy to a target.
While the systematic review showed an association between higher oxygen saturations and higher mortality, the BTS committee felt the review was not definitive on what the optimal target range should be. The suggested range of 94 to 96% in the review was based on the lower 95% confidence interval and the median baseline SpO2 from the liberal oxygen groups, along with the earlier 2015 TSANZ guideline recommendation.
Subsequently, experience during the COVID-19 pandemic has also made clinicians more aware of the feasibility of permissive hypoxaemia.[89] The BTS guidance is due for a review in 2023.
Management of oxygen therapy in patients in intensive care is specialised and informed by further evidence (not covered in this summary) that is more specific to this setting.[90][91][92]
Ensure respiratory isolation for all patients with suspected meningitis until they have received 24 hours of intravenous antibiotics.[16]
Apply droplet precautions until the patient has had 24 hours of effective antibiotic treatment, including:[16][75]
Single-room nursing
Surgical masks
Standard infection prevention precautions.
Give empirical intravenous dexamethasone to all adults with acute bacterial meningitis.[16][64]
[ 
]
Start dexamethasone shortly before or at the same time as antibiotic therapy.[16][64][93]
If antibiotics have already been started, dexamethasone may still be given for up to 12 hours after the first dose of antibiotics.[16][64]
Continue for 4 days if organism is confirmed to be Streptococcus pneumoniae or Haemophilus influenzae.[16][25][29][64]
If no cause is found, continue dexamethasone in practice, if clinical suspicion for bacterial meningitis remains high, and especially in the more severe spectrum of disease, which has a higher risk of long-term neurological sequelae.
Patients usually receive the full course of dexamethasone treatment as an inpatient.
Stop corticosteroid therapy if another organism is identified.[16][25][29][64]
Evidence: Corticosteroid therapy in bacterial meningitis – effectiveness
A 2015 Cochrane review found that adults and children with acute bacterial meningitis who were given corticosteroids (mostly dexamethasone) as part of their treatment had significantly lower rates of hearing loss compared with those not given corticosteroids. Adding corticosteroids did not reduce mortality or short‐term neurological sequelae.[94]
The review found 25 randomised controlled trials, involving a total of 4121 participants, of which 7 reported data separately for adults. Considering only the studies of adults, in the groups taking corticosteroids:
The rate of hearing loss was lower: 68 of 433 (15.7%) versus 90 of 411 (21.9%; relative risk [RR] 0.74, 95% CI 0.56 to 0.98; P=0.035; 4 studies)
There was a non-significant reduction in short-term neurological sequelae (RR 0.72, 95% CI 0.51 to 1.01, P=0.06; 4 studies)
There was a non-significant reduction in mortality rate (RR 0.74, 95% CI 0.53 to 1.05, P=0.09).
A subgroup analysis by high- versus low-income countries found:
There was no significant difference in mortality in adults between the group taking corticosteroids and those taking placebo in either income subgroup
Hearing loss in adults was significantly lower with corticosteroids than with placebo in the high-income subgroup (3 studies), but not in the low-income subgroup (1 study).
Another subgroup analysis by causative organism (this time including children as well as adults) found:
Corticosteroids protected against death in people with pneumococcal meningitis (RR 0.84, 95% CI 0.72 to 0.98; 17 studies of which 6 were in adults).
The review concluded that treatment with adjunctive corticosteroids was not associated with harm.
The 2016 European Society of Clinical Microbiology and Infectious Diseases guideline found no additional studies beyond those in this Cochrane review and concluded that these data support the use of corticosteroids in patients with bacterial meningitis in countries with a high level of medical care.[25] The UK joint specialist societies guideline distinguishes between organisms and recommends that corticosteroid treatment should be stopped if an organism other than S pneumoniae is identified.[16]
Evidence: Corticosteroid therapy in bacterial meningitis – timing of first administration
There is a lack of evidence on the timing of administration for corticosteroid therapy. Guidelines base their recommendations on expert opinion and differ in the advice they give.
The European Society of Clinical Microbiology and Infectious Diseases (ESCMID) guideline recommends that corticosteroids should be started with the first dose of antibiotics, whereas the UK joint specialist societies guideline recommends they are given either shortly before or simultaneously with antibiotics.[16][25]
The ESCMID guideline recommends that dexamethasone can still be started up to 4 hours after initiation of antibiotic therapy, whereas the UK joint specialist societies guideline recommends that if antibiotics have already been started, corticosteroids can still be given up to 12 hours after the first dose of antibiotics.[16][25]
Evidence: Corticosteroid therapy – stopping or continuing treatment
Guidelines suggest a 4-day course of corticosteroid therapy based on the causative organism, using evidence from a Cochrane systematic review.
A Cochrane review examining the effect of adjuvant corticosteroid therapy versus placebo on mortality, hearing loss, and neurological sequelae in people of all ages with acute bacterial meningitis found:[94]
Corticosteroids protected against death in pneumococcal meningitis (relative risk [RR] 0.84, 95% CI 0.72 to 0.98; 17 studies of which 6 were in adults)
In meningococcal meningitis, corticosteroids were associated with a non-significant reduction in mortality (RR 0.71, 95% CI 0.35 to 1.46; 13 studies of which 4 were in adults)
For children with meningitis caused by H influenzae, hearing loss was significantly reduced by corticosteroids (RR 0.34, 95% CI 0.20 to 0.59; 10 studies)
For children with meningitis caused by bacteria other than H influenzae, there was no significant beneficial effect on hearing loss (RR 0.95, 95% CI 0.65 to 1.39; 13 studies).
Based on the evidence from this Cochrane review, the European Society of Clinical Microbiology and Infectious Diseases guideline (covering adults and children) recommends that dexamethasone:
Should be continued for 4 days if the causative organism is H influenzae or S pneumoniae
Should be stopped if the patient is discovered not to have bacterial meningitis or if the bacterium causing the meningitis is a species other than H influenzae or S pneumoniae.
Similarly, the UK joint specialist societies guideline (covering adults) recommends that dexamethasone:
Should be continued for 4 days if the causative organism is S pneumoniae, or if no cause is found and pneumococcal meningitis remains most likely based on clinical, epidemiological, and cerebral spinal fluid parameters
Should be stopped if a cause other than S pneumoniae is identified.
Empirical antibiotics
Treat the majority of patients empirically as the causative pathogen is not always identified at the initial assessment.
Give empirical intravenous antibiotics to patients with presumed bacterial meningitis within 1 hour of presentation to hospital and ideally immediately after blood cultures.[16][25]
Do not delay starting antibiotics for lumbar puncture (LP). The need for a rapid LP has to be weighed against the desire to start antimicrobial treatment urgently.[16]
Some guidelines recommend giving antibiotics after LP (where LP is indicated and as long as LP is not delayed) to allow the best chance of definitive diagnosis.[16] The culture rate can drop off rapidly after 4 hours, making it difficult to identify the causative organism (but prompt molecular tests will still identify the causative organism even after antibiotics have been started).
If LP cannot be performed within 1 hour, give antibiotics immediately after blood cultures have been taken.[16]
Taking blood for culture also should not prevent administration of antibiotics within 1 hour of hospital presentation.[16]
In practice, if a patient has received an antibiotic in the community (i.e., if a general practitioner suspected bacterial meningitis clinically) that is different to the first-choice empirical antibiotic recommended by your institution, you should still give a dose of this empirical antibiotic in the accident and emergency department. However, if the antibiotic given in the community is the same as your first-choice empirical antibiotic, you should not duplicate the dose.
Follow your local protocol when prescribing antibiotics and seek advice from microbiology. Choice of empirical antibiotic is determined by epidemiology of causative organism and specific patient age groups.[16]
The most common cause of bacterial meningitis in immunocompetent adults <60 years is Streptococcus pneumoniae.[25]
In adolescents, group B Neisseria meningitidis is the most common cause of meningitis.[25]
In patients ≥60 years and immunocompromised adults, Listeria monocytogenes is the most common cause of meningitis.[25][29]
Otitis and sinusitis predispose to Haemophilus influenzae meningitis.[25][29]
Endocarditis predisposes to Staphylococcus aureus meningitis.[25][29]
Pathogens associated with specific disorders in immunocompromised patients | |
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Neisseria meningitidis meningitis[100] |
|
| |
| |
The UK joint specialist societies guideline on the diagnosis and management of acute meningitis and meningococcal sepsis in immunocompetent adults recommends the following empirical antibiotics:[16]
Give intravenous ceftriaxone or cefotaxime
For patients with penicillin or cephalosporin allergy, give intravenous chloramphenicol
Add intravenous amoxicillin (as cover for L monocytogenes) to the regimen for adults 60 years or older and those who are immunocompromised
For patients with penicillin or cephalosporin allergy, add in trimethoprim/sulfamethoxazole
If there is a risk of penicillin-resistant pneumococci or travel within the last 6 months, add intravenous vancomycin or rifampicin orally or intravenously. If you are unsure, check with a local infectious diseases or microbiology expert.
Seek expert advice when treating patients with suspected tuberculous meningitis.[43]
Current information on antimicrobial resistance is available:
De-escalate treatment as soon as appropriate, including switching from intravenous to oral antibiotic therapy. When making this decision consider response to treatment, change in disease severity, and contraindications to oral administration such as:
Patient is unable to swallow (e.g., impaired swallowing reflex, impaired consciousness)
Gastrointestinal malabsorption for functional or anatomical reasons.
Review route of administration initially on the ward round following admission and then daily thereafter.
Pathogen-targeted antibiotics
Target antibiotic treatment after the pathogen is identified through Gram stain, polymerase chain reaction testing, and culture.[25][29]
Consider narrowing treatment further, if appropriate, once the results of sensitivity testing are available or following consultation with a microbiologist.
If no pathogen is identified but you suspect bacterial meningitis and the patient responds to empirical treatment, continue this treatment for a total of 10 days.[16]
If you discharge a patient from hospital, prescribe oral antibiotics to complete the full duration of the antibiotic course according to culture sensitivity results.
Targeted antibiotic therapy[16] | ||
Pathogen | Antibiotic | Total duration in days |
Haemophilus influenzae | Continue intravenous ceftriaxone or cefotaxime or moxifloxacin.* | 10 |
Enterobacteriaceae | Continue intravenous ceftriaxone or intravenous cefotaxime and consult specialist microbiologist about local antimicrobial resistance. Use intravenous meropenem if you suspect an extended-spectrum beta lactamase organism. Use chloramphenicol instead of ceftriaxone or cefotaxime if the patient is allergic to penicillin. | 21 |
Streptococcus pneumoniae | Continue intravenous ceftriaxone or intravenous cefotaxime. If penicillin-sensitive, any of the following would be suitable: benzylpenicillin, ceftriaxone, or cefotaxime. If penicillin-resistant, continue ceftriaxone or cefotaxime. If penicillin-resistant but cephalosporin-sensitive, continue ceftriaxone or cefotaxime and add vancomycin or rifampicin. If both penicillin- and cephalosporin-resistant, continue ceftriaxone or cefotaxime and add vancomycin and rifampicin. Use chloramphenicol instead of a third-generation cephalosporin if the patient is allergic to penicillin. | 10, unless the patient has not recovered or has both a penicillin- and cephalosporin-resistant organism, in which case give 14 days of treatment |
Listeria monocytogenes | Give intravenous amoxicillin and stop ceftriaxone or cefotaxime. If the patient is allergic to penicillin, give trimethoprim/sulfamethoxazole. | At least 21 |
Staphylococcus aureus[25] | Give flucloxacillin monotherapy or a combination therapy with fosfomycin or rifampicin.[60] Do not give rifampicin and fosfomycin as monotherapy to avoid the development of resistance.[25][29] The decision to add rifampicin or fosfomycin to flucloxacillin, vancomycin, daptomycin, or linezolid is complex.[101] In UK practice, the addition of these drugs to the regimen is usually required in patients with severe disease needing treatment in intensive care. Use vancomycin for methicillin-resistant staphylococcal meningitis.[25][29] Use linezolid for vancomycin resistance (mean inhibitory concentration >2 micrograms/mL) or in cases of contraindications to vancomycin.[25][29] Consider adding rifampicin to vancomycin or linezolid when treating MRSA.[25][29] For patients with penicillin allergy, use vancomycin or linezolid together with rifampicin or fosfomycin. Do not give rifampicin and fosfomycin as monotherapy to avoid the development of resistance.[25][29] | At least 14 Consider other sites of infection, such as spinal epidural abscesses or endocarditis, which may require surgical intervention and prolonged antibiotic therapy[25] |
Mycobacterium tuberculosis | ||
Neisseria meningitidis | ||
*NOTE: In November 2018, the European Medicines Agency (EMA) completed a review of serious, disabling, and potentially irreversible adverse effects associated with systemic and inhaled fluoroquinolone antibiotics. These adverse effects include tendonitis, tendon rupture, arthralgia, neuropathies, and other musculoskeletal or nervous system effects. As a consequence of this review, the EMA now recommends that fluoroquinolone antibiotics be restricted for use in serious, life-threatening bacterial infections only. Furthermore, it recommends that fluoroquinolones should not be used for mild to moderate infections unless other appropriate antibiotics for the specific infection cannot be used, and should not be used in non-severe, non-bacterial, or self-limiting infections. Patients who are older, have renal impairment, or have had a solid organ transplant, and those being treated with a corticosteroid are at a higher risk of tendon damage. Coadministration of a fluoroquinolone and a corticosteroid should be avoided.[102] The UK-based Medicines and Healthcare products Regulatory Agency (MHRA) supports these recommendations.[103] For simultaneous fluoroquinolone and corticosteroid treatment in bacterial meningitis, consult senior clinicians and microbiology for a careful analysis of the risks and benefits. | ||
Give fluids to maintain normal haemodynamic parameters.[16]
Normal blood pressure for age in adults: ≥65 mmHg mean arterial pressure.
Urine output: >0.5 mL/kg/hour (a urinary catheter is required).
Lactate: <2 mmol/L.
Patients with uncomplicated meningitis tend to be relatively euvolaemic.[16][74]
Underhydration and overhydration have been associated with adverse outcomes in people with bacterial meningitis.[16][74]
Evidence from critically ill patients in general (not specifically just people with bacterial meningitis) suggests that there is no difference in benefit between normal saline and a balanced crystalloid (such as Hartmann's solution, [also known as Ringer's lactate] or Plasma-Lyte®), and therefore either choice of fluid is reasonable.[104][105] Check local protocols for specific recommendations on fluid choice.
Practical tip
Be aware that large volumes of normal saline as the sole fluid for resuscitation may lead to hyperchloraemic acidosis.
Also note that use of lactate-containing fluid in a patient with impaired liver metabolism may lead to a spuriously elevated lactate level, so results need to be interpreted with other markers of volume status.
Evidence: Choice of fluids
Evidence from two large randomised controlled trials (RCT) suggests there is no difference between normal saline and a balanced crystalloid in mortality at 90 days, and therefore either option is a reasonable choice for the resuscitation of critically ill patients.
There has been extensive debate over the choice between normal saline (an unbalanced crystalloid) versus a balanced crystalloid (such as Hartmann’s solution [also known as Ringer’s lactate] or Plasma-Lyte®). Evidence from critically ill patients points to no benefits from using a balanced crystalloid in preference to normal saline. Clinical practice varies widely, so you should check local protocols.
In 2021 to 2022 two large double-blind RCTs were published assessing intravenous fluid resuscitation in intensive care unit (ICU) patients with a balanced crystalloid solution (Plasma-Lyte®) versus normal saline. The Plasma-Lyte 148 versus Saline (PLUS) trial (53 ICUs in Australia and New Zealand; N=5037) and the Balanced Solutions in Intensive Care Study (BaSICS) trial (75 ICUs in Brazil; N=11,052), was published in 2021.[105]
In the PLUS study 45.2% of patients were admitted to ICU directly from surgery (emergency or elective), 42.3% had sepsis and 79.0% were receiving mechanical ventilation at the time of randomisation.
In BaSICS almost half the patients (48.4%) were admitted to ICU after elective surgery and around 68.0% had some form of fluid resuscitation before being randomised.
Both found no difference in 90-day mortality overall or in pre-specified subgroups for patients with acute kidney injury (AKI), sepsis, or post-surgery. They also found no difference in the risk of AKI.
In BaSICS, for patients with traumatic brain injury, there was a small decrease in 90-day mortality with normal saline - however, the overall number of patients was small (<5% of total included in the study) so there is some uncertainty about this result. Patients with traumatic brain injury were excluded from PLUS as the authors felt these patients should be receiving saline or a solution of similar tonicity.
A meta-analysis of 13 RCTs (including PLUS and BaSICS) confirmed no overall difference, although the authors did highlight a non-significant trend towards a benefit of balanced solutions for risk of death.[106]
Previous evidence has been mixed.
A 2015 double-blind, cluster-randomised, double-crossover trial conducted in four ICUs in New Zealand (N=2278), the 0.9% Saline vs. Plasma-Lyte for ICU fluid Therapy (SPLIT) trial, found no difference for in-hospital mortality, AKI, or use of renal-replacement therapy.[107]
However, one 2018 US multicentre unblinded cluster-randomised trial - the isotonic Solutions and Major Adverse Renal events Trial (SMART), among 15,802 critically ill adults receiving ICU care - found possible small benefits from balanced crystalloid (Ringer’s lactate or Plasma-Lyte) compared with normal saline. The 30-day outcomes showed a non-significant reduced mortality in the balanced crystalloid group versus the normal saline group (10.3% vs. 11.1%; OR 0.90, 95% CI 0.80 to 1.01) and a major adverse kidney event rate of 14.3% versus 15.4% respectively (OR 0.91, 95% CI 0.84 to 0.99).[108]
One 2019 Cochrane review included 21 RCTs (N=20,213) assessing balanced crystalloids versus normal saline for resuscitation or maintenance in a critical care setting.[109]
The three largest RCTs in the Cochrane review (including SMART and SPLIT) all examined fluid resuscitation in adults and made up 94.2% of participants (N=19,054).
There was no difference in in‐hospital mortality (OR 0.91, 95% CI 0.83 to 1.01; high quality evidence as assessed by GRADE), acute renal injury (OR 0.92, 95% CI 0.84 to 1.00; GRADE low), or organ system dysfunction (OR 0.80, 95% CI 0.40 to 1.61; GRADE very low).
Evidence: Underhydration and overhydration
Underhydration and overhydration are associated with adverse outcomes in patients with bacterial meningitis.[16][74]
The UK joint specialist societies guideline recommends that patients should be kept euvolaemic.[16]Other guidelines, including the 2008 European Federation of Neurological Societies guideline on community-acquired bacterial meningitis, make no recommendations on fluid management.[69]
A Cochrane review (updated in March 2016) found three randomised controlled trials (RCTs) of differing volumes of fluid given in the initial management of bacterial meningitis in children.[110] There were no RCTs in adults.
The meta-analysis found that there was a statistically significant difference in favour of maintenance fluid over restricted fluid for spasticity (relative risk [RR] 0.50, 95% CI 0.27 to 0.93; 357 participants) and seizures at both 72 hours (RR 0.59, 95% CI 0.42 to 0.83; 357 participants) and 14 days (RR 0.19, 95% CI 0.04 to 0.88; 357 participants).
However, the authors concluded that the evidence was of low to very low quality, and was insufficient to inform recommendations.
Nonetheless, the UK joint specialist societies guideline states that too much fluid replacement may worsen cerebral oedema, and, in the absence of high-quality evidence, does not recommend fluid restriction to reduce cerebral oedema.[16]
Report all cases of suspected bacterial meningitis to your local authority. This is a legal requirement in the UK under the Health Protection (Notification) Regulations 2010. Health Protection (Notification) Regulations 2010 Opens in new window
Notifiable causative agents are listed in schedule 2 of the Health Protection (Notification) Regulations 2010. Health Protection (Notification) Regulations 2010: schedule 2 Opens in new window
Of the organisms that commonly are identified to cause meningitis, the following are notifiable:
Haemophilus influenzae (invasive)
Legionella species
Listeria monocytogenes
Neisseria meningitidis
Shigella species
Streptococcus pneumoniae (invasive)
Streptococcus pyogenes (invasive)
Escherichia coli
Mycobacterium tuberculosis.
Check the protocol for the country where you are based.
Haemophilus influenzae type b (Hib)
In the UK, prophylactic rifampicin for household contacts will be initiated by the health protection team after notification.[16]
Hib vaccination should be given to all unvaccinated household contacts under 10 years.[16]
Pneumococcus
Contact management is not usually indicated for pneumococcal meningitis, as close contacts are not usually at increased risk of infection.[16]
Discuss clusters of severe pneumococcal infection in care homes with your local health protection authority.[16]
Check HIV status in all patients with meningitis.[16]
Investigate immunological status of patients with two or more episodes of pneumococcal meningitis.[16]
Perform computed tomography or magnetic resonance imaging in patients with a history of trauma, recent neurosurgery, rhinorrhoea, or otorrhoea to identify any source of cerebrospinal fluid leak.[16][23][24]
Assess all patients for long-term physical and psychological effects before hospital discharge.[16]
Refer all patients with confirmed or probable bacterial meningitis for medical follow-up within 6 weeks following discharge.[16]
Agree on a rehabilitation plan with the patient and/or their family/carers.[16]
Provide contact details of support organisations, such as:[16]
Refer all patients with suspected meningitis and/or meningococcal sepsis to hospital immediately (usually by blue-light ambulance in the UK).[16]
If there will be a delay of more than 1 hour in getting patients with suspected meningitis to hospital, give empirical intravenous or intramuscular antibiotics prior to hospital transfer.[16] Follow your local protocol. The British Infection Association recommends:[16]
Benzylpenicillin (intramuscular or intravenous) OR
A third-generation cephalosporin such as cefotaxime or ceftriaxone (intramuscular or intravenous).
Do not delay transfer to hospital by attempting to give parenteral antibiotics.[16]
Treat suspected meningococcal disease (not covered here) in the community immediately.[16] Follow your local protocol.
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