Facilitator Guide: Bacterial Meningitis BMB Block March 11/12, 2019 PART I LEARNING OBJECTIVES:
Develop clinical problem-solving and critical thinking skills Develop the ability to recognize and interpret clinical signs/symptoms and laboratory data Develop the ability to form a differential diagnosis based on the clinical presentation Develop the ability to select different courses of action in order to manage an emergency (time-sensitive) case
PATIENT CASE Chief Complaint: “My wife is so sick. Tell me she not going to die.” History of Present Illness: The patient, a 28-year-old woman, is confused and moaning on a hospital cart in the emergency department. The following history is provided by her husband: They just landed at Cincinnati/Northern Kentucky airport after returning from a trip to San Francisco. Yesterday, she was feeling generally unwell. Overnight, she developed a headache. This morning when they boarded the plane, she took two Tylenol because her headache was much worse and she felt like she was “running a temp”. The Tylenol seemed to help as she was able to sleep for most of the flight. Around Chicago, however, she started complaining continuously of a severe, unremitting headache and was “burning up”. The flight attendant documented a temp of 102.5, brought cool compresses, another two Tylenol, and notified the captain. By this time they were 30 minutes from Cincinnati. The plane was given priority landing and an ambulance was waiting to take the patient to your emergency department. PMHx: No chronic medical problems. Meds: Birth control pills. All: NKDA. Probe Question #1: What are the significant aspects of this patient’s history?
Symptoms of fever Headache worsening over the last 24 hours Deterioration of her mental status over 6 hours No chronic medical problems
Probe Question #2: What is your very preliminary differential diagnosis? Probe Question #3: What additional questions would you like to ask the patient’s husband?
Has she had other recent symptoms or medical problems? Has she had any recent sick contacts? Has she had any recent travel other than this trip to San Francisco? What type of work does she do? Any types of occupational exposures? Has she suffered any recent head trauma? How did she describe her headache? Where was her headache located? Does she have a history of headaches? Is there a family history of headaches or intracranial problems (e.g. aneurysms, brain tumors)?
Additional History: About a week ago, she had a “sinus infection” with congestion, nasal discharge, and intermittently feeling feverish. It seemed to get better two or three days ago. She has had no known sick contacts. She has had no other recent travel. She works in an accounting office, so there are no known occupational exposures. She has no recent history of head trauma. She described her headache as an intense pressure and pain. It hurt all over; it was not localized to one area. She does not have a history of headaches. There is no family history of headaches or other intracranial problems.
Probe Question #4: What simple bedside lab test should you perform at this time? Obtain a fingerstick blood glucose. This should be performed rapidly on any patient with altered mental status or an abnormal neurologic exam. It is quick and easy to perform, and if the glucose is low, it is easily treatable and can prevent severe long-term sequelae.
Additional Information: The patient’s bedside fingerstick blood glucose is 75.
Probe Question #5: What is your preliminary differential diagnosis?
Meningitis o Bacterial o Fungal o Atypical bacterial (e.g. TB) o Viral
Encephalitis – typically viral (e.g. HSV) Vector-born meningoencephalitis o Rocky Mountain spotted fever o Lyme disease Brain abscess Sepsis/systemic infection Subarachnoid hemorrhage Intracranial hemorrhage o Spontaneous o Trauma (remember, if domestic violence, history may not be forthcoming) Dural venous sinus thrombosis Status epilepticus TTP (Thrombotic thrombocytopenic purpura) Pre-eclampsia/eclampsia Toxin o Ingestion o Carbon monoxide Alcohol withdrawal Thyroid storm Hypoxia Electrolyte abnormality o Hyponatremia o Hypercalcemia
Physical Examination: General appearance: The pt. is a young woman who appears of normal development and nutrition, who is thrashing about and moaning on the hospital stretcher. Vital signs: Blood pressure: 135/90, Pulse: 128 (regular), Respirations: 18, Temperature: 38.4 C (101.2 F) (axillary). Room air O2 sat. 97%. Height: 5’7”. Weight: 140# (per husband). Skin: HEENT:
No lesions, no rashes/petechiae/purpura. No bruising or signs of trauma. No signs of head trauma. Pupils 4mm bilaterally and reactive to light. The patient does not follow commands, but eye movement grossly intact. No rhinorrhea or purulent drainage. Oropharynx clear. Neck: She screams when you try to flex her neck – probable nuchal rigidity. No masses noted. Lymph: No lymphadenopathy. Lungs: Respirations are not labored. Auscultation is difficult because of her moaning, but no abnormal or focal findings heard. Heart: Normal S1 & S2, as best you can hear. No obvious murmurs or rubs. Abdomen: Soft with no apparent tenderness. Bowel sounds seem present, although auscultation is difficult. No obvious masses, hernias, or organomegaly. Rectal exam: Normal tone. No stool in vault. Extremities: No edema. Neurologic: She does not answer questions or follow commands. She resists eye opening, but her eyes appear conjugate. Unable to assess for papilledema. She moves both arms and legs equally well as she is
writhing around. Sensory exam is difficult as the patient cannot fully cooperate, but she moves all four extremities to painful stimulus. Unable to participate in DTR testing as patient not relaxed. Negative Babinski bilaterally.
Probe Question #6: What physical exam findings are most important? How long do you think it would take to perform this exam noted above? Would you have skipped any parts of the exam in order to save time? Important positive/abnormal findings include:
Tachycardia Fever Nuchal rigidity Altered mental status
Important negative/normal findings include:
Normal blood pressure No rashes/petechiae/purpura (notable due to concern about potential meningoccal meningitis and associated meningococcemia) No focal neurologic finding beyond her altered mental status
It is reasonable to expect students to take approximately 10 min. to do the exam listed above. It is not necessary to perform a rectal examination as there is no focality beyond her altered mental status. Since time is critical, one should move quickly over any aspect that could not be done properly (e.g. DTR’s). The examination should be completed in about 5 minutes.
Probe Question #7: After your physical exam, how has your differential diagnosis changed?
Meningitis – very likely!!! o Bacterial – most likely cause due to rapid progession o Fungal o Atypical bacterial (e.g. TB) o Viral Encephalitis – typically viral (e.g. HSV) – also possible Vector-born meningoencephalitis – less likely due to incidence, lack of skin findings and time course o Rocky Mountain spotted fever o Lyme disease Brain abscess - possible Sepsis/systemic infection – less likely non-CNS source without other findings Subarachnoid hemorrhage – possible, but would not explain the fever. Also usually of very sudden onset Intracranial hemorrhage – possible, but would not explain the fever, unless hypothalamus involved o Spontaneous
o Trauma (remember, if domestic violence, history may not be forthcoming) Dural venous sinus thrombosis – possible, but would not explain the fever Status epilepticus – possible, doesn’t fit overall picture. But, this could be a result of the underlying process TTP (Thrombotic thrombocytopenic purpura) – unlikely with no petechiae/purpura Pre-eclampsia/eclampsia – less likely with no evidence of pregnancy Toxin o Ingestion – possible, would not explain all findings o Carbon monoxide – unlikely, as has not been alone, and others not affected Alcohol withdrawal – unlikely, as would not explain many of the findings Thyroid storm – less likely with nuchal rigidity and no neck mass Hypoxia – ruled out Electrolyte abnormality – less likely due to fever and nuchal rigidity o Hyponatremia o Hypercalcemia
Bacterial meningitis should be number 1, 2, and 3 on the DDx; as she has the combination of headache, fever, nuchal rigidity, and altered mental status. Please note: Not all patients with community-acquired bacterial meningitis have all of these findings. A fulminant viral encephalitis (e.g. herpes simplex) is a lower probability, but legitimate possibility. The students may have identified that the patient has a serious infection that is involving the brain.
Probe Question #8: Based on your differential diagnosis, what diagnostic testing do you want? Why do you want these tests?
CBC – check the platelet count. There are better options for making the diagnosis than the WBC, but noting an extremely high or low WBC is important. Renal profile – assess fluid status, confirm glucose, and assess renal function for medication use Urine pregnancy test – mainly to guide medication choices, also to rule out preeclampsia/eclampsia Head CT – to rule out structural process that would make an LP dangerous in the setting of altered mental status. Lumbar puncture (CSF cell count, glucose, protein, Gram stain and culture, PCR for HSV) – to look for meningitis Blood cultures – to help identify the causative organism Urine toxicology screen? Only if other testing negative
Probe Question #9: How much time do you think it will take to get these tests done? These tests will take approximately one hour to perform. For every one-hour delay in starting antibiotics, the mortality rate increases 30% (Harrison’s online).
Probe Question #10: Should you do these tests, or should you start treatment without delay? If you decided to treat without delay, which treatment(s) would you choose?
Treatment should be started right away. Initial treatment should be with intravenous ceftriaxone, vancomycin and dexamethasone. The clinical outcome in bacterial meningitis is determined primarily by how long it takes to start therapy. The faster treatment is initiated, the better the outcome. In bacterial meningitis, the selection of antibiotics is driven primarily by age of the patient, past medical history and location of acquiring the infection (outpatient versus inpatient). In this case, the most common organisms (strep pneumoniae 50%; and neisseria meningitides 30%) usually respond to ceftriaxone. Strep resistant to ceftriaxone is occurring more commonly, hence the use of IV vancomycin. IV dexamethasone reduces the harmful effects of the inflammatory response and when given early – with appropriate antibiotics -- reduced the mortality rate from 14% to 7%. Some would also start ampicillin to cover for listeria (very young, very old and/or immunosuppressed). Acyclovir also may be started even if the clinical picture is more consistent with bacterial meningitis given the high mortality associated with HSV. Response times for PCR for HSV can vary depending on the institution. As mentioned above, waiting to treat until all test results are obtained could greatly increase her mortality.
Probe Questions #11. What would you do after evaluating the patient and initiating anitbiotics? After treatment has been initiated, send the patient for a head CT scan and then subsequently perform a spinal tap. The blood tests and blood cultures would likely be sent while waiting for the antibiotics to arrive – 20 minutes after order is given. (You could imagine that depending on the communication between the ambulance in the emergency department, things could be waiting when the patient arrives.)
Test Results: Hemoglobin Hematocrit Platelet count White cell count Neutrophils – 75% Lymphocytes – 18% Monocytes – 4% Eosinophils – 2% Basophils – 1%
13.1 g/dL 40% 325,000 /mm3 16.2 X 103 /mm3
Serum Na+ Serum K+ Serum ClSerum HCO3Serum blood urea nitrogen (BUN) Serum creatinine Serum glucose
141 mEq/L 4.3 mEq/L 102 mEq/L 27 mEq/L 10 mg/dL 0.7 mg/dL 82 mg/dL
Urine pregnancy
Negative
Head CT
Normal
Lumbar puncture Opening pressure WBC RBC Glucose Protein Gram stain PCR for HSV
240 mm H2O (normal 80-180) 5,500 (98% PMNs) (normal <5) 20 8 (normal is 2/3 of serum glucose) 78 (normal 15-45) Gram + cocci in pairs Negative
TABLE OF NORMAL LABORATORY VALUES
Probe Question # 12: Based on the test results, what is your diagnosis? How sure are you (please give percent probability)? Bacterial meningitis, strep pneumonia (~99%) Since antibiotics were started prior to obtaining the spinal tap, the cultures may come back â&#x20AC;&#x201C; 48 hours later -- as negative. This is why it is helpful to send blood cultures prior to giving antibiotics, but only if it causes no delay in administration. The Gram stain could be helpful in identifying the most likely organisms (in this case revealed gram positive cocci in pairs as is seen in strep pneumoniae). More advanced testing (PCR) yields improved diagnostic information on the causative organism (consider sensitivity and specificity) that is not affected by antibiotics. The elevated WBC count (5,500/all neutrophils), protein of 78, and glucose of 8, all point strongly to acute bacterial meningitis as the diagnosis in this case.
Probe Question #12: Self-Directed Learning Question: a) List one additional question you have about the disease process discussed in this case for which you do not already know the answer. b) Research and provide an answer to this question. c) List the resource(s) that you used to answer the question. d) Provide your assessment of the credibility of the resource(s) that you used.
Probe Question #13: What additional resources did you use to help you with this case?
PART II Follow Up Question #1 If the patient defervesced and improved clinically over a week, and then remained afebrile but became unresponsive with a non-focal exam over several hours, what would you be concerned about? What test would be most important to get?
Answer: Obstructive hydrocephalus (rare but well described late sequelae). Emergency head CT. Follow Up Questions # 2 Does our emergency department have an emergency algorithm that should be applied to this case? Try http://emergencykt.com to find out.
Follow Up Question # 3 One of the core competencies is to improve the system with which we deliver our care. Can you think of a project that you could work on to achieve that goal?
Teaching Points What are the key points in her history and why are they important? Different sources list differing combinations of the â&#x20AC;&#x153;classicâ&#x20AC;? presentation of meningitis. Almost all patients, however, have at least two of the following: fever, neck stiffness, headache, and altered mental status. Early treatment is critical. Therefore, we need to be alert for bacterial meningitis in all patients with two of the four symptoms/signs listed above. Recommended Article: Clinical Features and Prognostic Factors in Adults with Bacterial Meningitis. NEJM 2004;351:1849-59.