Course:PostgradFamilyPractice/ExamPrep/99 Priority Topics/Fever

Fever - Key Features

1. In febrile infants 0-3 months old:
a) Recognize the risk of occult bacteria.
b) Investigate thoroughly (e.g., blood cultures, urine, lumbar puncture +/- chest X-ray).

CPS has an interesting guideline on measurement of fever. The summary is that rectal temperature >38 remains the gold standard for children under 5, and oral temperature >38 for children above 5 years old. Axillary temperature is reasonable for screening, but is not diagnostic. Tympanic remains controversial, in terms of accuracy.

Treatment based on age, as most fevers in children are viral and the risk of occult serious bacterial infection decreases with increasing age. There is significant debate over how to treat febrile children at present, due to increased vaccination and falling infection rates.

Serious bacterial infection (SBI) is a heterogenous category: meningitis, sepsis, osteomyelitis, septic arthritis, UTI, pneumonia, enteritis all crop up on the list.

You will see a lot of approaches break neonates down into <30 days, versus 30-90 days, versus 3-36 months. The evidence in this realm is changing pretty rapidly, and I could not find any current Canadian guidelines (the most recent CPS guideline I could find is from 1996, which is clearly insane to study from).

Causative organisms by age

AGE	LIKELY ORGANISMS	POSSIBLE EMPIRIC ANTIBIOTICS
Neonate	GBS, E .coli, S. aureus, Gr negs	Amp + gent or amp + cefotaxime, consider acyclovir
1-3 mod	Same as above and below	Ceftriaxone 50-100mg/kg (or cefotaxime) +/- ampicillin, cloxacillin
3-36 mod	S. pnemococcus, H. influenza, meningococcus	Ceftriaxone 50mg/kg IM/IV (100mg/kg if suspect meningitis). Alternatives: clinda, macrolide. Consider vanco if a lot of S. pneumo resistance

A few notes on this table: Ampicillin is added to cover Listeria - probably necessary up to 6-8 weeks. Vancomycin should also be considered if the source is thought to be skin/soft tissue, given MRSA rates. Acyclovir shouldn’t be given to every febrile neonate, but in the setting of maternal HSV, suspicious lesions, seizures, or a toxic/encephalopathic appearing child.

I TOXIC CHILD OF ANY AGE
These ones are easy - they all need aggressive investigation and management.

1. Admit

2. Do full septic workup

3. Empiric IV antibiotics based on age and local resistance patterns (see table) until cultures back

II NONTOXIC CHILD

NONTOXIC NEONATES (0-1 MONTHS)

These ones are also easy - they all need aggressive investigation and management.

- Greatest risk of SBI (12-13% of febrile neonates) and least likely to appear toxic

- These children all need to be aggressively cultured regardless of WBC count etc.

- Most often have UTI>bacteremia>meningitis>gastro>other

- Obvious viral URTI does not decrease the risk of a concomitant SBI (unlike in older children)

- Admit all, full septic workup including LP and possible HSV testing

- Empiric antibiotics +/- acyclovir until cultures back

What about the child who had a fever at home, but not in the ER? Check out this article if interested - http://www.cjem-online.ca/v6/n5/p343. In summary, a measured (not tactile) fever at home but not in-hospital is still associated with a pretty significant risk for infection in the 0-30 day age group.

NONTOXIC FEBRILE INFANTS (1-3 MONTHS)

These ones are tricky - they may not need as aggressive treatment as was previously recommended but guidelines are in evolution. There are no Canadian guidelines, for this age group, more recent than 1996 that I could find.

These children are less likely to have SBI than the <1mo age group and there are a variety of risk stratification criteria (Rochester, Baker etc.) Realistically speaking in practice, I expect most of us would manage this age group in consultation with a pediatrician.

I’m not going to regurgitate the Up To Date article for you. The current thinking is that, in the absence of evidence to the contrary, these children should still be broadly cultured and have a CBC and CXR. The need to do an LP, is controversial. The need for admission, is controversial. Giving a dose of ceftriaxone for empiric coverage and discharging, is controversial. Given how the topic is worded, I think your safest bet would be to answer questions on the side of conservative investigation and management in this age group -- ie, pan-cultures, admission, and broad spectrum antibiotics. Just be aware that this may not necessarily be the case out in the real world.

NONTOXIC FEBRILE CHILDREN, 3-36 MONTHS

These children are your “normal” office patients. They are much less likely to have SBI or occult bacteremia, if well-looking.

There is a big role for clinical judgement in this age group as opposed to guidelines. Sorry!! I’m not going to insult y’all by saying things like “common sources for infection in this age group are acute otitis media, pneumonia etc. etc. bla bla bla.” Anyways the 99 topic question as I can tell isn’t so focused on this age group.

2. In a febrile patient with a viral infection, do NOT prescribe antibiotics.

Almost all of the “typical” family medicine infections are viral. Sinusitis - >98%. Sore throat - >90% in the under 5 and over 18 age group, and about 70% in the 5-18 age group. Bronchitis - >98% (COPD patients are an exception here, they warrant antibiotic treatment). Have a look at the ARI series in Canadian Family Physician, they are really brief articles, 1 page each, on common URIs. UTIs on the other hand, are almost always bacterial.

3. In a febrile patient requiring antibiotic therapy, prescribe the appropriate antibiotic(s) according to likely causative organism(s) and local resistance patterns.

I think by now everybody probably has their list of antibiotics for the common stuff we see. I will give you my list, which I try very hard to have be evidence-based - ie, appropriate for the bug, but not overkill.

Coverage for common URI bugs: Amoxicillin, 40mg/kg/day in kids, the current American Academy of Pediatrics guideline for AOM calls for high dose at 80mg/kg/day for improved inner ear penetration and activity against resistant strains. Macrolides, Septra, and 3rd gen cephalosporins are reasonable second line choices (though I tend to think that giving cefuroxime for otitis media falls into the “overkill” category, personally)

Coverage for pneumonia - first line for outpatients is a macrolide or doxycycline if they are otherwise healthy. First line for inpatients is a respiratory quinolone. The Canadian Thoracic Society guidelines can be found at http://www.respiratoryguidelines.ca/sites/all/files/Community-acquired-Pneumonia-Guidelines-2000.pdf, knock yourself out. The algorithm on risk stratifying patients for admission versus discharge is interesting and educational but I won’t reproduce it here.

Coverage for UTI - Septra and Macrobid are first-line. Cipro provides renal coverage, which Macrobid does not and Septra does not very well, I believe.

Hopefully the more esoteric stuff will come up in other people’s topics.

4. Investigate patients with fever of unknown origin appropriately (e.g., with blood cultures, echocardiography, bone scans).

5. In febrile patients, consider life-threatening infectious causes (e.g., endocarditis, meningitis).

6. Aggressively and immediately treat patients who have fever resulting from serious causes before confirming the diagnosis, whether these are infectious (e.g., febrile neutropenia, septic shock, meningitis) or non-infectious (e.g., heat stroke, drug reaction, malignant neuroleptic syndrome).

Keep in mind that there is fever without source (what we usually see, a toddler with a fever but it’s not obvious where it’s coming from), versus fever of unknown origin. FUO is fever lasting for 3 weeks without obvious source; the differential here is autoimmune, neoplastic, infectious, and “miscellaneous” (drug-induced, hepatitis, other rare zebras). Check out the comprehensive review. I think the key is that there is a broad differential with some “can’t miss” diagnoses, such as TB, HIV, osteomyelitis, endocarditis, lymphoma, malignancy, RA, etc. The suggested initial workup from the above AFP article suggests CBC, electrolytes, LFTs, blood cultures, urine cultures, CXR, TB skin test, CXR, and ESR with further investigation depending on results.

I believe topic #5 and most of #6 is fairly self-explanatory. If you need to familiarize yourself with early goal directed therapy for sepsis here is the Surviving Sepsis Campaign pocket guide. The full guideline is on their website, but it’s pretty wordy and this gives you the basics.

There is an entire topic on meningitis so I am not going to cover that.

A brief word on a few other topics they mentioned:
Endocarditis - patients with abnormal heart structure are at high risk (congential defects, valvular defects, prosthetic valves, cardiomyopathy). Other high risk patients are injection drug users and those with prior endocarditis. Most cases caused by gram positive cocci specifically Strep viridans, Staph aureus, Staph epidermidis. You may hear about HACEK - these are gram negative infections responsible for 5-10% of endocarditis. Don’t make me name the bugs I promise you you won’t remember.

There are detailed diagnostic criteria for endocarditis but fortunately the letters after my name are not going to be FRCP(C) so I’m not going to go over them here. Just remember that the presentation is nonspecific but can include anything on a spectrum from acute toxic illness with high fever, to vague and nonspecific symptoms such as weakness, arthralgia, fatigue, malaise, anorexia. Your physical exam should identify all the classic heavily pimped signs named after physicians from the 1800s. Labs may or may not show anemia, elevated WBC, elevated CRP. Blood cultures may or may not be positive, but you should get 2 sets 12 hours apart. TTE may or may not show vegetations, TEE is still the gold standard if you are suspicious and the TTE is negative. These people need long, long courses of antibiotics (6 weeks at a bare minimum).

Febrile Neutropenia - here’s a great guideline, from Alberta Health Services
In summary, Fever >38.3 degrees, ever, or >38 degrees for one hour (ie, 38-38.3 degrees) PLUS ANC <0.5 in a patient who has received chemo in the last month is febrile neutropenia. You need to identify the site of infection with CBC, LFTs, electrolytes and renal function, blood cultures, urine cultures, CXR, sputum culture. LP does not need to be done routinely. Do not do a rectal exam. I believe in an exam setting you would be safe so long as you identified an appropriate broad spectrum antibiotic such as ceftazidime, imipenem, meropenem, pip-tazo. Vancomycin is probably not empirically necessary but circumstances may suggest its use.

7. In the febrile patient, consider causes of hyperthermia other than infection (e.g., heat stroke, drug reaction, malignant neuroleptic syndrome).

Hyperthermia - a nonphysiologic response which overrides the set point (remember, fever tends to be a result of a raised hypothalamic set point).

Heat stroke - core body temperature >40.5ºC with associated CNS dysfunction in the setting of a large environmental heat load that cannot be dissipated. Complications include ARDS, DIC, renal or hepatic failure, hypoglycemia, rhabdomyolysis, and seizures. Mortality up to 20%.

There are two types of heat stroke:

Classic (nonexertional) heat stroke: in individuals with underlying chronic medical conditions that either impair thermoregulation or prevent removal from a heat e.g. cardiovascular disease, neurologic or psychiatric disorders, obesity, anhidrosis, extremes of age, and use of drugs such as anticholinergic agents or diuretics

Exertional heat stroke: generally occurs in young, otherwise healthy individuals (e.g. athletes, military recruits) who engage in heavy exercise in high ambient temperature and humidity without access to salt and water. May be the first sign of increased susceptibility to malignant hyperthermia.

Related problems: Heat cramps – muscle cramps after exercise in heat secondary to salt loss and ingestion of hypotonic fluids. Temp is normal, skin is moist and cool. Rx: rest, oral rehydration with salt solution, rarely IV NS.

Heat exhaustion: results from salt and water losses, minimal increase in core temp. Present with N+V, headache, diaphoresis, cramps. Rx: rest in cool place, cooling and rehydration. Avoid strenuous exercise for 2-3 days.

Malignant hyperthermia (MH) is a rare genetic disorder that manifests following treatment with anesthetic agents, most commonly succinylcholine and inhaled anaesthetics. Early findings are muscle rigidity , sinus tachy, increased CO2 production, and skin cyanosis with mottling. Hyperthermia up to 45ºC occurs minutes to hours later; core temp rises 1ºC every 5 to 60 min. Hypotension, dysrhythmias, rhabdomyolysis, electrolyte abnormalities, DIC, and mixed acidosis are common.

Neuroleptic malignant syndrome (NMS) is an idiosyncratic reaction to antipsychotic agents. In addition to hyperthermia, NMS is also characterized by "lead pipe" muscle rigidity, altered mental status, choreoathetosis, tremors, and evidence of autonomic dysfunction, such as diaphoresis, labile blood pressure, and dysrhythmias.

Serotonin syndrome may be confused with NMS, but is a distinct entity that includes agitation, confusion, hyperthermia, diaphoresis, tachycardia and rigidity. Seen with SSRIs, but also L-tryptophan, LSD, lithium, L-dopa and the MAOIs.

Treatment of hyperthermia
Antipyretics don’t help because they affect hypothalamic set-point, which isn’t the problem.
ABCs
Cooling to 39.5C rectal with ice packs, bath, fans, even cold peritoneal lavage. Do not use ETOH rubs because a toxic amount can be absorbed cutaneously.
Inhibit shivering with benzos or chlorpromazine (don’t use this in NMS).
Labs – CBC, LFTs, INR, PTT, renal function, CK for rhabdo etc.
Mostly supportive Rx and specific Rx for MH (dantrolene) and NMS (stop neuroleptic, try bromocriptine etc.)

8. In an elderly patient, be aware that no good correlation exists between the presence or absence of fever and the presence or absence of serious pathology.

Study Guide

Fever

Resources

Canadian Pediatric Society measurement of fever
http://www.cjem-online.ca/v6/n5/p343
Canadian Thoracic Society http://www.respiratoryguidelines.ca/sites/all/files/Community-acquired-Pneumonia-Guidelines-2000.pdf Community acquired pneumonia guidelines]
http://www.aafp.org/afp/2003/1201/p2223.html
Surviving Sepsis Campaign pocket guide
Alberta Health Services febrile neutropenia guidelines