The Responder’s Guide to Meningitis

This CE activity is approved by EMS World Magazine, an organization accredited by the Continuing Education Coordinating Board for Emergency Medical Services (CECBEMS) for 1 CEU. To take the CE test that accompanies this article, go to www.rapidce.com to take the test and immediately receive your CE credit. Questions? E-mail editor@EMSWorld.com.

Objectives

• Define what is meningitis
• Discuss the epidemiology of meningitis
• Review evaluation of the meningitis patient
• Discuss prehospital management of the meningitis patient

The meningitis outbreak of late 2012 began in September when a patient in Tennessee was diagnosed with Aspergillus fumigatus meningitis 46 days after being injected with an epidural steroid.¹ A subsequent investigation led by the Tennessee Department of Health, CDC and North Carolina Department of Health and Human Services identified 8 more patients. Fast-forward to November 1, and we’ve now confirmed 414 patients in 19 states, 30 of whom have died.

What happened is still being determined. However, what is known is that more than 17,500 vials of preservative-free methylprednisolone acetate, from three different drug lots, were packaged in volumes of 1, 2 and 5 mL and shipped to 75 distribution sites in 23 states. These vials were later found to be infected with the fungus Exserohilum rostratum, which has been associated with patients developing:^1,2

• Fungal meningitis or nonbacterial and nonviral meningitis;

• Basilar stroke following epidural injection;

• Septic arthritis or osteomyelitis of a peripheral joint following injection;

• Spinal osteomyelitis or epidural abscess.

Of patients aged 23–91 years, 91% of those experiencing ill effects from their steroid injections have been diagnosed with fungal meningitis, which is considered a very rare complication from epidural injections.¹ As meningitis is a serious and life-threatening illness often not easily distinguished from other emergencies, this outbreak has real and potential impacts on EMS systems all over the country.

What Is Meningitis?

Anytime -itis is seen at the end of a part of anatomy, think inflammation. Meningitis is the inflammation, or swelling, of the meninges. The meninges are three layers of connective tissues that surround and protect the brain and spinal cord. In order from outer to inner, the meningeal layers (see Figure 1) are the:

• Dura—The tough and relatively inelastic outermost membrane;

• Arachnoid—The middle layer, thin and spider web-like;

• Pia—The innermost, vascularly rich layer that tightly hugs the brain and spinal cord.

EMS providers most often remember the dura, as it is the separating membrane for epidural and subdural hematomas. However, as seen in Figure 1, the meninges extend down the length of the spinal cord. Cerebrospinal fluid takes up the space between each layer to maintain near-frictionless movement of the membranes against one another and help the central nervous system move electrolytes and nutrients, maintain acid-base balance, transport hormones and neurotransmitters, and maintain a balance of intracranial pressure.

Additionally, the meninges make up a significant part of the blood-brain barrier, and this barrier extends throughout the CNS. Most of the time it helps protect the CNS by making infection difficult. However, once an infectious material passes the blood-brain barrier, infection can spread rapidly.

Epidemiology

In the United States the annual incidence of meningitis is 4,100 cases, with 500 deaths.³ While this number appears small, meningitis remains a major source of morbidity and mortality in developing countries. The worst outbreak occurred in 1996 in West Africa: 250,000 persons were infected, and 25,000 died.⁴ While not important for daily medicine in the United States, it is important to remember that locations throughout the developing world still have outbreaks, and EMS providers traveling on medical mission trips may visit locations where meningitis remains an epidemic problem.

According to the CDC, there are five different types of meningitis: bacterial, viral, parasitic, fungal and noninfectious. The type is based on the source pathogen. Bacterial and viral meningitis are the most commonly heard of, and the bacteria or virus enters the meninges via the bloodstream. Between these, viral meningitis is by far the more common, diagnosed in more than 90% of cases, and it is not easily communicable. In these cases inflammation typically is found along the dorsum of the brain.³ Infection may also enter the CNS along a nerve such as the olfactory nerve following sinusitis.

Less-common routes for exposure include direct penetrating and blunt trauma, migration of sepsis, neurosurgery and instrumentation. Instrumentation procedures include lumbar puncture and epidural injection, the latter of which has been the primary exposure route for the current fungal meningitis outbreak. In a lumbar puncture (commonly called a spinal tap), the CSF is directly accessed by penetrating the dura with a needle. In contrast, an epidural injection involves depositing fluid in the space external to the dura but beneath the ligamenta flava and other spinal cord-containing ligaments and structures.

Bacterial meningitis is described as either acute or subacute. Acute meningitis typically has symptom development within a day and is nearly always bacterial in nature. Patients with acute bacterial meningitis develop severe symptoms rapidly and often require emergent intervention. These severe cases are often meningococcal, staphylococcal, haemophilus or tuberculosis in nature and have a mortality rate of nearly 10%.⁴ Fortunately nearly 75% of bacterial meningitis cases are subacute, with symptoms developing over 1–7 days. Bacterial meningitis can be spread through direct contact as well as by respiratory droplets, saliva and mucus.

Viral meningitis is caused by the nonpolio enterovirus in 85% of cases and is often self-limiting in nature.⁵ Children under 5 have the greatest risk for developing viral meningitis, and it is spread through fecal contact (think changing diapers) as well as oral and respiratory routes. The risk of transfer is very low, fortunately, and treatment is typically conservative.

Fungal meningitis is most commonly caused by Cryptococcus. While fungal infections can spread from the bloodstream, they are most often exposed directly from a host site into the central nervous system, such as through a lumbar puncture. In the current fungal meningitis outbreak, exposure has been through the deposition of contaminated steroids just outside the dura lining of the CSF-filled cord, which has allowed the fungus to quietly track inward over time. Fortunately fungal meningitis cannot be transmitted from person to person. This means that once meningitis is known to be from a fungal etiology, respiratory precautions are not needed. Be careful, though: Until the specific organism is identified through culture growth in a laboratory, it is nearly impossible to distinguish fungal, viral and bacterial meningitis by other assessment data.

Parasitic meningitis is extremely rare, with only 32 cases reported to the CDC between 2001–10.⁶ Its rarity is fortunate, because when it does occur it is caused by the amoeba Naegleria fowleri and is fatal within 1–12 days of symptoms appearing. Like fungal meningitis, it is not contagious, but parasitic meningitis has no effective treatment or cure.

Any meningitis that is not parasitic, fungal, viral or bacterial is termed noninfectious meningitis. Because it is not infectious, there is no way to transmit this illness from one individual to another. Potential causes of noninfectious meningitis include trauma, cancer, lupus and neurosurgery.

Exposure

Infections do not typically begin to cause symptoms the moment the pathogen enters a patient. Pathogens enter the body at an exposure, which is the event or incident when the patient first encounters the pathogen. For this current fungal epidemic, the exposure has been defined as the epidural or paraspinal injection of preservative-free MPA from a known infected lot. The period from when a pathogen enters a patient until symptoms first begin to appear is known as the incubation period. Bacterial meningitis has an incubation period of 3–7 days. In this current fungal meningitis outbreak, the median incubation period is 16 days, but symptoms have taken between 4 and 42 days to develop.¹ One of the true hazards of bacterial meningitis is that it becomes contagious before symptoms appear; this is one of the reasons why individuals living in close quarters are at increased exposure risk. Routine vaccination for healthcare professionals, including EMS providers, is not currently recommended by the CDC because incidence is very low and traditional droplet and contact precautions can eliminate most transmission risks. Vaccination is recommended for healthcare professionals who have HIV or suppressed immune systems or travel to third-world countries where the incidence is high.

Evaluation

Many equally dangerous conditions can mimic the symptoms of meningitis. Figure 3 lists several differential diagnoses to consider. Ruling in or out any illness on this list, including meningitis, requires a thorough history and physical examination.

As with all patients, obtain a thorough SAMPLE history. Spend a great deal of time focusing on the development of the patient’s signs and symptoms. In particular, when evaluating a patient who may have any form of meningitis, quickly determine symptom onset and how quickly any symptoms may be worsening. The more slowly symptoms progress, the less worrisome they are. Patients with meningitis may complain of headaches, nausea, lethargy, confusion and photophobia. Photophobia is a fairly regular complaint for patients with meningitis, but it is neither sensitive nor specific for the illness. This means its presence alone does not mean meningitis, nor does its absence exclude it. Consider photophobia together with the patient’s other symptoms.

Additionally, it is essential to determine whether the patient may have been around anyone known to have had meningitis or if the patient has been living in close quarters, where the risk for the illness greatly increases. While always sensitive, it is appropriate to ask about the presence of any sexually transmitted diseases. Both HSV and HIV infections increase the risk of meningitis.

When inquiring about a patient’s history and medicines, look for a history of oral antibiotics. As many as 40% of patients diagnosed with bacterial meningitis have been initially managed with oral antibiotics, possibly due to initial missed diagnoses.⁴

Perform a thorough physical exam when meningitis is suspected. In most patients it makes sense to begin at the head. Patients with photophobia will likely still have normal pupillary responses and no evidence of eye injury. Papilledema, or swelling of the optic disc, is rarely observed but suggests meningitis, brain abscess or another condition causing increased intracranial pressure. EMS providers may observe papilledema through the presence of swollen veins within the eyes, an enlarged blind spot and headaches. Neck tenderness may be present, particularly upon movement. Nuchal rigidity exists when a patient has difficulty flexing their neck forward in the absence of any neck trauma. It is present in about a third of meningitis patients.

Examine the chest carefully. Listen to lung sounds in all fields. Patients who are later diagnosed with pneumococcal meningitis often have pneumonia as well. New-onset heart murmurs are common with certain bacterial meningitis cases.

Globally, fever is the most common symptom, vomiting may be observed in about a third of patients, and a rash occurs in nearly half. Roughly half of all adult meningitis patients present with either Kernig’s sign or Brudzinski’s sign. Kernig’s sign is determined by placing the patient supine with their knees and hips both bent at 90 degrees. The provider then attempts to straighten the knees. If this causes hamstring pain, the test is positive. Brudzinski’s sign is positive if, while the patient is laying supine, neck flexion causes the patient flex their hips as well.

At times patients may also have ataxia, which is difficulty walking straight (almost appearing drunk). Be sure to complete a physical exam thoroughly enough to rule out differential diagnoses, particularly stroke, though this may not always be possible in the prehospital setting. Keep a sharp eye for any signs of a local infection source as well. Sepsis is a very grave complication of meningitis; see the May 2012 EMS World CE article, “Managing Sepsis in the Adult Patient,” for more.

While the supposed classic triad of symptoms for meningitis (headache, photophobia, nuchal rigidity) is quite rare, a meta-analysis of patients demonstrated that the absence of fever, nuchal rigidity and altered mental status can rule out meningitis in more than 99% of cases.⁴ Patients with meningitis and altered mental status have a significantly increased risk for long-term neurological damage.

While there is no set vital sign pattern for meningitis, hypertension is common. Additionally, if patients experience an increase in their intracranial pressure, bradycardia may develop as a Cushingoid response. Anticipate tachypnea any time fever is present.

Be highly suspicious of meningitis whenever a patient presents with headache, nuchal rigidity, fever and mental status changes. While the diagnosis is not certain, the best technique for ruling out meningitis when all four symptoms are present is through a lumbar puncture to test for infectious materials.

Management

Prehospital providers have the opportunity for involvement during two different phases of a patient’s management. Prior to a meningitis diagnosis, EMTs and paramedics may see patients in a 9-1-1 setting, particularly when patients present with acute bacterial meningitis and have rapidly progressing symptoms. When responding for a patient whom you learn has had a sore neck and then presents with mental status changes, be sure to keep meningitis in your list of differential diagnoses. EMS has a particularly important role in collecting information. While on scene, gather as much history as possible from bystanders and the surroundings and relay this to the ER staff, as it can aid in diagnostics.

When meningitis is suspected during prehospital care, immediately ensure contact and respiratory isolation precautions, and alert the emergency department early so they can have an isolation room available. While providing patient care, providers need to wear surgical masks (N95 masks are not currently recommended) to prevent exposure. Alternatively, patients not requiring supplemental oxygen can wear surgical masks. Consider low-dose oxygen therapy via nasal cannula to maintain an SpO₂ around or above 94%. Routine administration of high-flow oxygen is unnecessary in most cases. Cardiac monitoring may be beneficial, as it is possible for cardiac dysrhythmias to develop. Focus prehospital care on stabilizing the patient’s vital signs and managing symptoms. For example, consider administering an antiemetic to patients with nausea or vomiting. During transport, maintain all patients in a position of comfort and keep the lights turned low. While bright lights won’t hurt meningitis patients, they can cause discomfort.

Particularly in the acute phase of care and when patients present with altered mental status, anticipate the need for fluid resuscitation and the development of seizures. Whenever possible establish IV access in patients suspected of having meningitis and initiate fluid therapy early. If patients have severe sepsis, they may need up to 6 liters of fluid to establish euvolemia. Pediatric patients with suspected meningitis may need 20-mL/kg fluid boluses followed by fluid maintenance therapy typically established at a rate of 4 mL/kg for the first 10 kg, 2 mL/kg for the next 10 kg, and an additional 1 mL/kg for each additional kilogram of body weight. Should seizures develop, treat them following local protocols.

Management of any pain present, including headaches and neck stiffness, will only help the patient feel better and will not impair a physician’s diagnosis.

For management of meningitis patients during interfacility transfers, see the sidebar on page xx.

Prevention

While there is no standard vaccination available for adults, patients having several risk factors may be targeted with prevention efforts. Because newborns are born with immature immune systems, they are at increased risk of bacterial meningitis. In June 2012 the FDA approved MenHibrix for children as young as 6 weeks and as old as 18 months as a vaccination against several pathogens that commonly cause bacterial meningitis in children.⁷ A meningococcal vaccine is recommended by the CDC for adolescents, people living in close quarters and people with immune disorders or post-splenectomy.

When exposed to a confirmed meningitis case, medical providers are administered chemoprophylaxis for H. influenzae, N. meningitidis and S. pneumoniae. These nasally administered drugs help prevent infection from developing but do not combat it should the pathogen take hold.

Post-transport

Following the transport of any suspected meningitis patient, regardless of etiology, or the interfacility transport of a confirmed bacterial meningitis case, thorough decontamination of the ambulance and transport stretcher is essential. There are many commercial chemical cleaning solutions; however, a 1-to-100 bleach-to-water solution is effective as well. If you use a commercial solution, be sure to follow the manufacturer’s cleaning recommendations.

Inside the ambulance, every horizontal and vertical surface needs proper cleaning. The need for this was highlighted in a 2008 study that tested for the presence of bacteria on the surfaces of ambulance patient compartments and found that all surfaces tested positive not only for bacterial growth, but for four identified bacteria prone to antibiotic resistance.⁸ Then in 2009, 1 of 3 EMS provider stethoscopes tested positive for MRSA-resistant bacteria.⁹ The message: Don’t forget to clean your stethoscope as well. Failure to properly decontaminate surfaces a patient touches risks infecting other patients.

Figure 2: Who’s at Risk for Meningitis?⁴

• Extremes of age:60

• Medical history of: diabetes mellitus, renal/adrenal insufficiency, cystic fibrosis, immunosuppression, HIV, splenectomy, sickle cell disease, cancer

• Those in crowed living situations (e.g., military, college dorms, homeless shelters, group homes, skilled nursing facilities)

• Anyone known to have been exposed to another with meningitis

Figure 3: Differential Diagnoses to Consider

• Meningeal carcinomas

• Seizures

• Stroke

• Encephalitis

• Brain or spinal abscess

• Brain neoplasms

• Subarachnoid hematoma

• IV drug abusers

Interfacility Transfers

Patients with meningitis may not stay at hospitals where they were diagnosed, and may require transfer to tertiary-care hospitals. While these patients will have received specific diagnoses, ongoing careful monitoring remains important, and treatment is focused on the specific cause of the infection.

All patients being transferred require close monitoring and may need intensive-level care. In severe acute bacterial meningitis, patients may be found intubated with increased intracranial pressure. These patients may be receiving frequent diuresis with furosemide or mannitol. Should the patient be found intubated, paramedics need to transport while tightly controlling the patient’s end-tidal CO₂ between 30–35 mmHg. When EtCO₂ falls below 25 mmHg, any ischemia in the central nervous system worsens.

Bacterial meningitis is treated with aggressive antibiotics designed to attack the specific bacteria causing the infection. Patient age is important in deciding antibiotic coverage, in particular for Listeria, as risk is greatest under 5 and over 50 years old. Treatment regiments vary, but typical standard initial coverage includes vancomycin, ceftriaxone, acyclovir (for viral causes), dexamethasone (for inflammation) and ampicillin (for younger and older patients). The routine administration of broad-spectrum antibiotics is recommended until a specific bacterium is identified.

Long-term neurological damage is possible with bacterial meningitis, and these patients may require extended nursing care. It is reasonable to expect to see such patients during interfacility transports should their impairments be more severe. Patients with permanent neurological impairment from meningitis may have:⁴

• Hearing loss;

• Blindness;

• Paralysis or focal paralysis;

• Permanent ataxia;

• Seizures;

• Hydrocephalus;

• Subdural effusions;

• Cerebral atrophy.

Administration of the steroid dexamethasone has been shown to decrease morbidity in patients with meningitis. Dexamethasone decreases long-term neurological damage by decreasing inflammation of the blood-brain barrier. As the inflammation decreases, barrier permeability decreases as well. While prehospital administration of steroids is unnecessary, an infusion may be seen if transferring these patients to tertiary care.

Fungal meningitis requires treatment with aggressive antifungal drugs and is based on the type of fungus growing in the patient. In the current outbreak, with the pathogens Exserohilum rostratum and Aspergillus, patients are being treated with an antifungal called voriconazole dosed at 6 mg/kg every 12 hours.⁴ As many as 7 different antifungal drugs may be considered based on the type of fungus causing meningitis.

Viral meningitis is often self-limiting within about 10 days, and treatment is focused on maintaining patient comfort and treating symptoms. While viral meningitis (inflammation of the meninges themselves) is not contagious, the virus can be, so isolation precautions may still be necessary.

Management of noninfectious meningitis is driven by the etiology. It is impossible to anticipate what treatment patients may be receiving upon EMS arrival for transport. The benefit of this is, however, that noninfectious sources are not contagious and cannot expose the transport team.

When preparing a patient with meningitis for interfacility transport, take time to determine which infusions have been given and ask if any need to be continued. Should a specific drug being infused be new to the provider, ask the transferring physician the infusion rate and dose, common side effects and drug interactions. During longer transports a new drug infusion may need to be initiated. Be sure to identify when a drug infusion needs to be started, as many of these drugs are given at closely timed intervals.

States Receiving Infected Vials

States with facilities that received infected vials of methylprednisolone acetate as of November 27, 2012:

California

Connecticut

Florida

Georgia

Idaho

Illinois

Indiana

Maryland

Michigan

Minnesota

New Hampshire

New Jersey

New York

Nevada

North Carolina

Ohio

Pennsylvania

Rhode Island

South Carolina

Tennessee

Texas

Virginia

West Virginia

References

1. Centers for Disease Control and Prevention. Multistate outbreak of fungal infection associated with injection of methylprednisolone acetate solution from a single compounding pharmacy—United States, 2012. MMWR, 2012 Oct 19; 61(41): 839–42.

2. Centers for Disease Control and Prevention. CDC Responds to Multistate Outbreak of Fungal Meningitis and Other Infections, www.cdc.gov/HAI/outbreaks/currentsituation/.

3. Thigpen MC, Whitney CG, et al. Bacterial meningitis in the United States, 1998–2007. NEJM, 2011; 364: 2,016–25.

4. Razonable RR. Meningitis, https://emedicine.medscape.com/article/232915-overview.

5. Wan C. Viral Meningitis, https://emedicine.medscape.com/article/1168529-overview.

6. Centers for Disease Control and Prevention. Parasitic Meningitis, www.cdc.gov/meningitis/parasitic.html.

7. Lowes R. FDA Approvals: Combo Meningitis Vaccine for Infants, www.medscape.org/viewarticle/766119.

8. Alves DW, Bissell RA. Bacterial pathogens in ambulances: results of unannounced sample collection. Prehosp Emerg Care, 2008 Apr–Jun; 12(2): 218–24.

9. Merlin MA, Wong ML, et al. Prevalence of methicillin-resistant Staphylococcus aureus on the stethoscopes of emergency medical services provdiers. Prehosp Emerg Care, 2009 Jan–Mar; 13(1): 71–4.

Kevin T. Collopy, BA, FP-C, CCEMT-P, NREMT-P, WEMT, is the performance improvement coordinator for Vitalink/Airlink in Wilmington, NC, and a lead instructor for Wilderness Medical Associates. Contact him at kcollopy@colgatealumni.org.

Sean M. Kivlehan, MD, MPH, NREMT-P, is an emergency medicine resident at the University of California, San Francisco and a former New York City paramedic. Contact him at sean.kivlehan@gmail.com.

Scott R. Snyder, BS, NREMT-P, is EMT program director for the San Francisco Paramedic Association. Contact him at scottrsnyder@me.com.