Meningitis in Intensive care medicine. Data is collected from Harrison 19th edition, recently published papers, Cochrane review, and google search.

1. MENINGITIS IN INTENSIVE
CARE MEDICINE
DR. MAYUR GANVIR.
MD ANAESTHESIA
IDCCM(CRITICAL CARE
MEDICINE)
JUPITER HOSPITAL, INDIA

2. Meningitis, also termed arachnoiditis or leptomeningitis, is an inflammation of the
membranes that surround the brain and spinal cord, thereby involving the arachnoid, the pia
mater, and the interposed CSF.
Bacterial or pyogenic meningitis is an acute meningeal inflammation secondary to a
bacterial infection that generally evokes a polymorphonuclear response in the CSF.
Aseptic meningitis refers to a meningeal inflammation without evidence of pyogenic
bacterial infection on Gram’s stain or culture, usually accompanied by a mononuclear
pleocytosis
Encephalitis- Brain tissues is injured by bacterial or Viral infections.
Abscess- Focal infections involving brain tissue with capsule.
Cerebritis- Focal infections involving brain tissue without capsule.
The clinical triad of meningitis Fever + Neck stiffness + altered mental status is,
unfortunately, present in less than half of adult patients who have bacterial meningitis . Non
Specific Signs and Symptoms.. Goal- early administration of appropriate antibiotics.

7. History and physical examination should be carried out systematically
to identify the category in which the patients belong.
– Travel history (malaria, dengue, typhus, arbovirus infection)
– Drug history (steroids, other immunosuppressive)
– Trauma (splenectomy)
– Symptoms of ENT infection
– Neurosurgery
– Medical history of immunosuppressive disease, tuberculosis
Take isolation precaution :
Proper respiratory isolation precaution should be taken in patients with
suspected bacterial meningitis.
The patient should wear mask during transportation.

8. Menigism
Nuchal rigidity
Nuchal rigidity is the inability to flex the neck forward due to rigidity of the neck muscles; If
flexion of the neck is painful but full range of motion is present, nuchal rigidity is absent.
Cervical Spine disease- False positive test
Kernig's sign
Is Positive when the thigh is flexed at the hip and knee at 90 degree angles, and
subsequent extension in the knee is painful (leading to resistance).This may
indicate subarachnoid hemorrhage or meningitis.
Patients may also show opisthotonus—spasm of the whole body that leads to legs
and head being bent back and body bowed forward.
Brudzinski's neck sign
The appearance of involuntary lifting of the legs when lifting a patient's head off
the examining couch, with the patient lying supine.

10. Other signs attributed to Brudzinski
Brudzinski's reflex, in which passive flexion of one knee into the
abdomen leads to involuntary flexion in the opposite leg, and
stretching of a limb that was flexed leads to contralateral extension.
Symphyseal sign, in which pressure on the pubic symphysis leads
to abduction of the leg and reflexive hip and knee flexion.
Cheek sign, in which pressure on the cheek below the zygoma leads
to rising and flexion in the forearm
Petechiae and purpura generally are associated with
meningococcal meningitis, although these skin manifestations may
be present with any bacterial meningitis

11. Initiate empirical treatment

13. Criteria have been suggested for obtaining a head CT scan prior to
the LP in suspected bacterial meningitis.
• Head trauma
• Immuno-compromised state
• Recent seizure (within the last 7 days)
• Abnormal level of consciousnes.
• Focal weakness, abnormal speech
• Abnormal visual fields or gaze paresis.
• Inability to follow commands or answer questions appropriately.
• A history of any of the following : mass lesions, focal infection,
or stroke
An absolute contraindication to an LP is the presence of infection in
the tissues near the puncture site.
Precaution INR < 1.4, Platelet counts >50,000.

14. CSF Examination
• Cell count and type
• Protein
• Glucose (simultaneous blood glucose estimation is important; CSF
glucose value is normally 60–70% of blood glucose)
• Adenosine deaminase (ADA) (if tuberculosis is suspected)
• Gram stain, culture, and sensitivity
• Acid-fast bacilli (AFB) stain
• India ink for cryptococcal infection
• DNA PCR for herpes virus
• Cryptococcal antigen
• TB PCR and BACTEC TB culture
• Pneumococcal antigen
A sample of CSF should be preserved by the laboratory for further
testing.
Blood cultures and other basic investigations need to send for bacteremia.

16. One caveat to remember is that the CSF findings in bacterial
meningitis may not always yield the classic results.
Reasons for a lack of classic CSF findings in bacterial meningitis
include:
• Partially treated meningitis (eg, prior antibiotics)
• Time of LP (is it early in course of the disease before the patient
mounts a response, or late in the course?)
• The patient’s condition (is the patient able to mount a response
to the invading organism or is the patient immunosuppressed or
has an over- whelming infection?).
• CSF lactates has been used when a patient has had prior
antibiotic therapy, which likely makes the CSF culture- and gram
stain-negative.
• Normal CSF Lactate <35 mg/dL.(4 milli Mol/L)
• Bacterial/Fungal CSF lactates>35 mg/dL
• Viral CSF Lac< 35 mg/dL

17. Latex agglutination - The clumping of cells such as bacteria or RBCs in the
presence of an antibody. The antibody or other molecule binds multiple particles
and joins them, creating a large complex. Positive in meningitis caused
by Streptococcus pneumoniae, Neisseria meningitidis, Haemophilus
influenzae, Escherichia coli and group B streptococci.
Serotyping - Group of microorganisms classified together based on their cell
surface antigens (virulence, lipopolysaccharides in Gram-negative bacteria),
presence of an exotoxin or other characteristics which differentiate two members
of the same species.
•Limulus amebocyte lysate (LAL): An aqueous extract of blood cells
(amoebocytes) from the horseshoe crab, (Limulus polyphemus).
LAL reacts with bacterial endotoxin or lipopolysaccharide (LPS), which is a
membrane component of “Gram negative bacteria”.
•Polymerase chain reaction(PCR) is a technique used to amplify small traces of
bacterial DNA

18. Pathophysiology of Meningitis

20. Cascade of events in
meningitis.
IL = interleukin; TNF =
tumour necrosis factor;
PAF = platelet- activating
factor; ICP = intracranial
pressure; CPP = cerebral
perfusion pressure.
Major complications
result because of
immune response to the
invading pathogen
rather than from direct
bacteria induced tissue
injury.

22. • Ampicillin is added in special situations where Listeria may be a pathogen
(such as the elderly, those who have impaired immunity including patients who
have HIV, and newborns).
• Meropenem is an alternative drug for the cephalosporins, while
• Trimethoprim- sulfamethoxazole is an alternative drug for ampicillin.
• Vancomycin penetration into the CNS is mainly dependent upon meningeal
inflammation.
• Rifampin(600 mg/day) has good CSF penetration and in vitro activity against
many meningeal pathogens, but when used alone, resistance develops quickly.
Therefore, rifampin must be used in combination with other antimicrobial drugs
• Controversy for Dexamethasone- Probably because it decreases meningeal
inflammation, it significantly lowers therapeutic drug levels in the CSF, which
has led to clinical treatment failures in adults.

23. Dexamethasone (10 mg) or placebo was administered 15 to 20 minutes before or with the
first dose of antibiotic and was given every 6 hours for four days.
Result-
• Treatment with dexamethasone was associated with a reduction in the risk of an
unfavorable outcome measured by Glassgow scale..
• Treatment with dexamethasone was also associated with a reduction in mortality
(relative risk of death, 0.48; 95 percent confidence interval, 0.24 to 0.96; P=0.04)

24. The evidence is current to February 2015.
We identified 25 trials,
including 4121 participants with acute bacterial meningitis of which
seven were performed in adults (over 16 years old), two included
both children and adults and the other were performed in children.
In 22 studies the corticosteroid used was dexamethasone, in three
others hydrocortisone or prednisone were used.
Nine studies were performed in low-income countries and 16 in
high-income countries.

25. This review found that the corticosteroid dexamethasone did not significantly
reduce the death rate (17.8% versus 19.9%). Patients treated with corticosteroids
had significantly lower rates of severe hearing loss (6.0% versus 9.3%), any
hearing loss (13.8% versus 19.0%) and neurological sequelae (17.9% versus
21.6%).
A sub group analysis for different bacteria causing meningitis showed that patients
with meningitis due to Streptococcus pneumoniae (S. pneumoniae) treated with
corticosteroids had a lower death rate (29.9% versus 36.0%), while NO effect on
mortality was seen in patients with H. influenzae and N. meningitidis.
In high-income countries, corticosteroids reduced severe hearing loss, any
hearing loss and short-term neurological sequelae. There was no beneficial effect
of corticosteroid therapy in low-income countries.
Dexamethasone increased the rate of recurrent fever (28% versus 22%) but was not
associated with other adverse events.

26. Cryptococcus Neoformans- Non HIV/ Non transplant patients-
Induction therapy- Amphotericin B 0.7mg/kg /day + Flucytosine 100 mg/kg/day in 4 div. doses
For atleast 4 weeks if CSF culture results are negative after 2 weeks of treatment.
Consolidation therapy- Fluconazole 400 mg/d for 8 weeks.
Organ transplant – Lipo. Amp B(3-4 mg/kg/d or AmB lipid complex(5mg/kg/d) +
Flucytosine 100 mg/kg/d for atleast 2 weeks or till cultures turn out to be negative.
f/b Fluconazole 400-800 mg/d for 8-10 week course.
If cultures negative after 10 weeks then fluconazole 200 mg/d for 6 months to 1 year continued.
HIV patients- Lipo. AmpB + flucytosine for 2 weeks f/b fluconazole 400-800 mg/d for 8 weeks
and life long Fluconazole 200 mg /day

27. Histoplasma Capsulatum – Amp B ( 0.7-1.0 mg/kg/day) for 4-12 weeks or
till cultures are Negative.
Maintainence – Itraconazole 200 mg BD for TDS for atleast one year.
Coccidiodes Immitis- High dose Fluconazole 1000 mg/day(monotherapy) or
Amp B(0.5-0.75 mg/kg/d) for more than 4 weeks.
Intrathecal Amp B(0.25-0.75 mg/d three times weekly for 4 weeks f/b life long
Fluconazole 400 – 800 mg/d to prevent relapse should be continued.
Most common complication of fungal meningitis is HYDROCEPHALUS.
Ventriculostomy can be used till fungal cultures are negative, after which VP
shunt should be created.
Syphilitic meningitis-Aqueous Penicillin G in dose of 3-4 million U every 4 h
for 10-14 days.
f/b Benzathine Penicillin 2.4 million units IM once a week for 3 weeks.
CSF examination to be done every 6 months till 2 yrs.
Failure of CSF pleocytosis to resolve or an increase in CSF VDRL titer by 2 or
more requires repeat treatment

28. Differential Diagnosis.
• Viral Meningoencephalitis( Herpes Simplex Virus encephalitis, mimics Bact. Meningitis.
Findings on CSF ,Neuroimaging & EEG differentiates Viral from Bacterial.
CSF- lymphocytic pleocytosis.
MRI- High signal intensity in orbitofrontal,anterior & medial temporal lobes.
EEG-distinctive periodic pattern.
• Rickettsial disease(Rash Begins in wrist & Ankles within few hours palms & Soles)
Diffuse erythematous MaculopapularPetechial PurpuricSkin necrosisGangrene
Biopsy of Skin- Immunofluorescent staining.
• Sub Arachnoid Hemorrhage- Severe headache with blurring of vision.
Sometimes associated with fever..
• Pontine Bleed
• Chemical Meningitis- rupture of tumor cells in to CSF( Cystic glioma or craniopharyngioma
Epidermoid or dermoid cyst)
• Drugs : Amphetamine, OP posining,Atropine , TCA toxicity.
• Meningitis associated with inflammatory disorders such as Sarcoid, SLE, Behcet’s disease.
• Neuroleptic malinganant Syndrome( Central Dopamne antagonism)
• Serotonergic Syndrome
• Malignant Hyperthermia
• Endocrine abnormalities(Thyrotoxicosis)

29. Acute complications
• Shock
• Respiratory failure/distress/arrest Apnea.
• Altered mental status/coma
• Increased intracranial pressure
• Seizures
• Disseminated intravascular coagulation (DIC).
• Subdural effusions
• Subdural abscess
• Intracerebral abscess
• Increased intracranial pressure.
• Cerebral Herniation
• Death

30. Sequelae
• Seizure disorder
• Impaired intellectual functioning Impaired cognition
• Personality changes
• Dizziness
• Gait disturbances
Focal neurologic deficits:
• Deafness/sensorineural hearing loss (most common in H influenzae)
• Blindness
• Paralysis
• Paresis
Central nervous system structural sequelae/complications
• Hydrocephalus
• Brain abscess
• Subdural abscess
• Subdural effusion
• Subdural empyema
• Epidural abscess
• Cerebral thrombosis
• Cerebral vasculitis