Thread by @JayKinariwala

Humanity has but three great enemies: fever, famine and war; of these, by far the greatest, by far the most terrible, is fever. -Sir William Osler

That’s why temperature is one of the “vital signs” (not pain🤨)

So if you have ever wondered how body controls🌡 & never got an answer beyond - somewhere in 🧠hypothalamus; here’s an explanation.
🤕 is admitted H&H 4 SAH + IVH. This is the temp📈-shows, patient started spiking 🌡@ 24hrs & peaked ~72hrs. Cultures ⏲ ABX started on admission.

38.3 C = magic number for most of us to trigger “pan-culture” + “broad spectrum ABX” to fight off infection.

Does every fever needs to be addressed with ABX?? - probably not.

This is a #MedTwitter about Central fever aka neurogenic fever. From basics to treatment approaches.

Beautiful yet simple illustration from Nieuwenhuys neuroanatomy I always refer to.. @PeterMLawrence1 by #ChristiaanvanHuijzen #illustration

First, let’s answer this question.. How any of us remember hypothalamic nuclei??

Which of the hypothalamic nucleus is the Fever center and thermoregulatory center?

The thermoregulatory mechanism is fascinating. Like every regulatory system, you need an input to get an output. So here we go..

a) Input:
I] Cutaneous thermal receptors
ii] Visceral and spinal thermal receptors
b) Output
I] Skin
ii] Brown Fat
iii] Muscle.

The cutaneous & viscero-spinal receptors send afferent to median Pre-optic nucleus. The pre-optic area (POA) is known as a ‘fever center’ aka thermoregulatory center. From there, the efferent pathways regulate the temp by 3 different mechanisms.

Note that there’s another factor involved here - Prostaglandin E2. PGE2 is produced in response to systemic inflammation as a terminal product of the COX pathway. Pre-optic area is exquisitely sensitive to PGE2. PGE2 production is ⬆️, thermogenesis & heat conserving mechanisms ⬆️

3 ways thermoregulatory mechanism is controlled:
I]Skin-cutaneous vasoconstriction ⬇️ heat loss
ii]Brown fat=slow thermogenesis-⬆️ in BAT thermogenesis,(metabolism & HR that are evoked by stimulation of POA neurons are reversed by⛔️GABA-A
iii]Muscle-Shivering=faster thermogenesis

when inflammatory response 2/2 infection causes ⬆️temp 👉🏻 upregulation of heat production 👉🏻 controlled by hypothalamus; & set temp does not exceed 41C usually. So if core🌡>41 C, probably you’re dealing non-infectious process,e.g.hypothalamic dysregulation/drug induced

So, we know by now that any insult to hypothalamus can potentially cause central fever but how about spinal cord?
Can injury to spinal cord cause central fevers? Leave your response.

Other than hypothalamus
A)Brainstem:
-raphe-spinal path modulate cutaneous vasoconstriction
-ventromedial medulla⬆️BAT
-ventrolateral medulla & periaqueductal gray ⛔️BAT
B)Spinal Cord:
-sympathetic preganglionic neurons modulate BAT & heat loss, controlled by segmental inputs

So yes, in fact spinal cord injuries can cause central fever.
PMID: 27556002
Cervical, thoracic & in some cases, lumbar spinal cord injuries have been reported to cause central fever. Complete injury is more likely to cause central fever compared to incomplete.

When to suspect central🤒?
HISTORY! Onset,🌡pattern&neuro exam.

-ve cultures+chest XR
diag of SAH/IVH/tumor
onset of🤒<72 hrs of admission
☝🏻predicted central🤒with probability of .90 (PMID:24100963)

But always do infectious work up bcz central🌡is still diagnosis of exclusion.

How dangerous is hyperthermia&why should we be aggressive about it?
Every 1°C⬆️🌡=13%⬆️BMR
🐀 in which intraischemic 🧠🌡was ⬆️ to 39C during insult had⬆️mortality @3D post-ischemia 2/2 neuronal injury in cortex, CA1 hippocampus, striatum & thalamus compared to normo🌡ischemic🐀

When exposed pts with spinal cord ischemia(SCI) in warm water ~45 mins, pts with SCI had core 🌡⬆️ of 3.6°F compared with 1.6°F in control= impaired thermoregulation in SCI.
There’s a term called “quadriplegic fever” for pts who have several months long hypothermia after SCI.

Treatment strategies:
-NSAIDS (which⛔️COX pathway👉🏻⬇️PGE2)/Tylenol -surface cooling v/s intravascular cooling.
-brompcriptine
-baclofen

Surface cooling has its own limitations such as inability to use in awake / non intubated pts & paradoxical shivering requiring sedation.

Bromocriptine is a D2 receptor agnoist which acts in hypotalamus and striatum. It reduces paroxysmal autonomic hyperactivity and thereby controls temperature. Usually used dose is 2.5 - 5 mg TID, some may use higher.
PMID:28348904

Baclofen is a GABA-A agonist which acts in raphe nuclei to reduce BAT, thereby reducing temperature. Usually used dose is ~20 mg/day.
PMID:24855623

Also, keep in mind various hyperthermic toxidromes which have a specific treatment and be sure to rule them out. Here’s very useful chart by @nickmark on @icuonepage. Be sure to check this out.

Malignant hyperthermia guidelines 2020
PMID: 33399225

Moral:
1.Perform thorough investigation for infectious causes including hyperthermic toxidromes. History & 🌡pattern are the most important.
2. Do not let 🤒 stay ⬆️for too long in pts with neurologic 🤕. It has worse functional neurologic and cognitive outcomes.

@EmoryNeuroCrit @EmoryCCC @Capt_Ammonia @CajalButterfly @caseyalbin @ksuchdev @VarunPhadke2 @NeuroICUne @neurocritical @CritCareReviews @rkchoi @SrinivasMeghana @sigman_md @JimmySuhMD