Neuropathic pain in Guillain-Barre-Syndrome

We use the case of a mildly affected GBS patient with severe neuropathic pain to discuss the latter’s pathophysiology in general and the treatment for neuropathic pain in particular.
There is an excellent review article in BMJ 2014 which hints at the various drugs on the horizon, including some known substances whose application in neuropathic pain seems feasible (see below).

Neuropathic pain

  • Prophylaxis: in order to reduce the occurrence of neuropathic pain there is a good rationale for prophylactic treatment in certain cases, such as amputation, Zoster and nerve surgery, although not much good data has been published.
  • Classify: distinguish NP with autonomic features from that without, central versus peripheral (the latter often with autonomous signs)
  • Diagnosis: recognize the core features of pain character with good PPV (radiation, allodynia, hyperalgesia, autonomous sign if present, distribution along affected nerve structures)
  • Basic treatment
    • Stick to the basics: Despite the fact, that we Neurologists tend to think that NP is so special, we forget that basic nonsteroidal analgesics do work in NP; there is even a good pathophysiologic reason for that, since local cytokine production is influenced by at least the antiinflammatory substances (not acetaminophen, though).
    • Opiates: next is opiates, most often as a bridge to other approaches – still highly effective and reasonably well tolerated
    • alpha 2 delta blockers (gabapentinoids) work on the dorsal root ganglion and have been shown to be effective in many prototypical diseases
    • Na blockers (carbamazepine, phenytoin, lidocaine, lamotrigine)
    • NASRIs including tri- and tetracyclics and mirtazapin, as well as venlafaxine and duloxetine
  • Local treatment: only if the pathophysiological proces is focal – capsaicin and lidocain patch
  • Advanced treatment: for more advanced NP, ketamine seems to be the agent of choice as an NMDA blocker with all the problems arising. Further ideas could be: Baclofen, Clonidin. Many anticonvulsants (apart from those above) have been tested, not many survived, except in some diseases (trigeminal neuralgia for instance -> topiramate)
  • Experimental or future therapies: Allopurinol (ADP antagonist), Aprepipant (NK1 blocker), Memantine, Amantadine (both mild NMDA blockers), Cannabinoids (good preclinical data, moderate effect), cytokine inhibitors, NGF blockers

Pain in Guillain-Barré-Syndrome

I hesitate to repeat all the information to be found in the literature. Still it has to be said that pain is very prevalent, often preceding and also often following GBS, can take several forms (backache, interscapular, distal, skin, myalgia, …) and is often severe enough to run through the above list. Here is a good review article in Neurologia on this from 2015. The best case series has been published in Neuroloy in 2010.



Fever is an often raised problem in neurocritical care and stroke medicine. Here are some notes from todays lecture.


  • Infectious causes
  • Drugs (PHE, allopurinol, heparin, minocycline, neuroleptics, serotonergic)
  • other central fever forms (in particular in SAH: impending vasospasm), localizing to the hypothalamus, the third ventricle or the pons.

Management. Regardless of your threshold for fever or hyperthermia, you need to work it up systematically.

  • History: course of fever, is it still rising, drugs
  • Examination: is the body trying to heat or cool (is it fever or hyperthermia?)
  • Examination: sources of infection
  • Labs: apart from the obvious, think of troponin and procalcitonin (the latter if sepsis is assumed)

Therapy. There are some contexts in which fever or hyperthermia is not to be tolerated: stroke, MI, non-stable tachyarrhythmia. Remember that in the case of sepsis, it is probably better tolerated.

In the case of stroke, we know the following:

  • temperature is bad (outcome and mortality-wise)
  • it is safe to try to lower temperature (cf. PAIS study)
  • it is hard to lower temperature (the Kallmünzer/Kollmar publications)

It is not really clear

  • whether it really helps to lower temperature
  • what threshold to use
  • what methods are efficient

In our Stroke Unit, we decided to introduce a 3 layer approach:

  • 37,5°C: low-dose paracetamol or metamizol (4 x 500 mg)
  • 38°C: physical cooling and high dose (4 x 1000 of either)
  • 38,5°C: combination therapy and forced physical cooling
  • 39,5°C: desperate measures

Desperate measures, in particular for central dangerous fever (> 40°C)

  • Dantrolen
  • Baclofen
  • Lytic cocktail (block any neurotransmitter that might be involved in fever generation; since we don’t know which might be, block all of them) using anticholinergically acting neuroleptics + antihistamines + antiserotonergics + pethidine

The alveolar gas equation

A patient is in respiratory distress, SaO2 deteriorates and you wonder how to turn round the situation. Apart from other diagnostics, you get an arterial blood gas and analyse pH, pCO2 and elytes. Yet the core value is pO2 and this is the hardest to analyse. There are no normal values for pO2, unless you know the FiO2, the temperature and the age of the patient. The one most important medical equation for intensive care is the alveolar gas equation (AGE), which is actually quite easy to derive:

1. O2 streams into the alveolus with the breathing gas, which consists of ambient air (possibly enriched with O2) and water vapor (saturated by the nose, trachea and bronchi) – so it comes with a partial pressure of

  •  (atmospheric pressure – water pressure) x inspiratory O2 quotient


  • Now we are used to getting atmospheric pressure as hPa and not in Torr, but our BGA values tend to be in Torr (aka mmHg), so you have to convert the units. In Augsburg, atmospheric pressure is about 1020 hPa, which amounts to 768 mmHg. Water pressure is 47 mmHg.
  • The inspiratory O2 quotient is easy, if no O2 is supplied (21%), but gets problematic if nasal prongs or a mask without reservoir are used, because they don’t provide a predictable FiO2. Nasal prongs deliver from 30% to at most 40% (the latter only if you turn up the flow to ridiculous levels). Normal face masks deliver between 40% und 60%, again depending on the flow. Non-rebreather (reservoir) masks can deliver 100% only, if you (can) close both inlet valves, otherwise you end up with (about) 80%.

2. Now O2 not only streams into the alveolus through breathing, but also is taken up by the blood, but the amount is hard to measure (we don’t know much about our own work, so we can’t  know how much the patient works either, so we cannot compute how much oxygen he needs). But we get that information from the CO2 in the alveolus, because every CO2 has to have been metabolized from O2 through glycolysis. Depending on what we burn with O2, we get between 1,2 and 0,7 CO2 for every O2 (this is the respiratory quotient), but it is usually taken as 0,8 in intensive care. So we spend O2 in an amount proportional to

  • alveolar CO2 / respiratory quotient

The funny thing is that CO2 diffuses exceptionally well through the various alveolar layers, so we may assume that alveolar CO2 is roughly equal to arterial CO2, so that O2 spent is proportional to

  • arterial CO2 / respiratory quotient

Since dividing by 0,8 is about as good as multiplying by 1,25 or maybe 1,2, the latter expression reads

  • 1,2 * PaCO2

[Here comes the mathematician: we talked about income and spent O2 being proportional to these expressions, but not about the real values. That you can still compute with pressures rather than volumes is not completely obvious – but follow the complete math here.]

3.The whole AGE reads

  • P_alveolar O2 = FiO2 * (P_atm – P_H2o) – 1,2 * PaCO2 = FiO2 * 721 – 1,2 * PaCO2    [values for Augsburg, 11th floor, stroke unit]

This, of course, holds only under steady state conditions (O2 and CO2 have time to diffuse, be metabolized and so on; no change in diet) and proper ICU diets.


  • I find it not too hard to do the math in my head, but ICU docs usually just ignore the CO2-part, using FiO2 * 600 as a rough estimate for expected alveolar PO2. In fact, the Horowitz index is a very crude simplification of the AGE. If you know that high CO2(as in COPD) and low atmospheric pressures (such as on Mount Everest)  obscur things, you may actually use these simplifications in practice.
  • How do you use the AGE? You compare your arterial PO2 to the expected, i.e., alveolar PO2, subtract the higher from the lower (forming the alveolar-arterial oxygen difference PAaO2) and use this as a marker for the severity of your lung problem. Note that real hypoventilation (as in being sedated) should not really increase your PAaO2.
  • Nowadays, we know that advanced lung disease may interfere with a lot of the assumptions of the AGE, so beware with ARDS and COPD patients.

Herniation syndromes

This most classical of all Neurointensive-care-topic is – in my eyes – not only very important, but also quite hard to understand. If you belive Plum/Posner, it alls seems quite simple, but the details are often wrong. This starts with the reason for pupil dilatation in tentorial herniation (there are at least 3 different ways to achieve it and sometimes more than one applies), it goes on with the role of midline shift, the horizontal and vertical displacement and so on.

Here are my core teaching messages:

  • The third nerve runs between the SCA and PCA.
  • Inspect your CT completely, thinking about pressure and tissue shifts. Look at the midline, the mesencephalon, the third nerve, the pyramidal tract, the ARAS, the thalami, the uncus, the falx etc. Look everywhere.
  • Midline shift is (in stroke and ICH) irrelevant, if nothing else happens.
  • Pupils and drowsiness need not happen together.
  • Think about why the pupils dilate, the pt is drowsy, he vomits in each patient. The mechanism can be different each time.
  • Operation only helps if it heals the pathological mechanism.