Discussion

Mechanical ventilation increases the risk of mortality up to threefold when compared to nonmechanical ventilation subjects. In addition, it increases the risk of nosocomial pneumonia and length of hospital stay. ^{Reference Zhu, Wang and Kang11,Reference He, Wang and Zhu12} Twenty-nine percent of patients in our cohort required mechanical ventilation, like other cohorts. ^{Reference Durbin7} Treatment in GBS is aimed at curbing the immune response that causes damage to the myelin or axon of the peripheral nerves. However, even if patients are diagnosed and treated early, 20–30% have a poor long-term functional outcome and 5% die. ^{Reference Netto, Taly and Kulkarni13-Reference Levison, Thomsen and Andersen15} Both intravenous human immunoglobulin and PEs are equally effective in the treatment of GBS. ^{Reference Galnares-Olalde, López-Hernández and García-Grimshaw1} In our center, we have both therapies; however, we decided to treat with intravenous human immunoglobulin patients with GBS who enter the institution requiring mechanical ventilation for two reasons: 1) because a large percentage of these patients have hemodynamic compromise due to cardiovascular dysautonomia, PEs would increase the risk of worsening the hemodynamic state and 2) intravenous human immunoglobulin is easier to make available for immediate initiation of treatment in our institution.

Mechanical ventilation is a risk factor for poor functional outcomes (short and long term) in patients with GBS, but in patients with prolonged ventilation, the prognosis works, it is even more discouraging. In our population only 22% of patients recovered independent gait at 6 months of follow-up. ^{Reference Walgaard, Lingsma and Ruts5,Reference Fletcher, Lawn, Wolter and Wijdicks16} Risk factors include rapid and severe progression of muscle weakness and involvement of lower cranial nerves (VII, IX, and X). These clinical variables are incorporated into the EGRIS scale, which is the most widely used to assess the risk of mechanical ventilation on admission. ^{Reference Shang, Zhu and Baker6} In our cohort, patients without mechanical ventilation were admitted to the hospital in a greater number of days from the onset of symptoms versus patients requiring ventilation [6 (IQR 2–9) vs 3 (IQR 2–6) days, p = < 0.001]. Interestingly, there was no significant difference between patients with prolonged ventilation versus nonprolonged ventilation (Table 1).

The presence of albumin-cytological dissociation in CSF represents nerve root involvement. ^{Reference Brettschneider, Petzold and Süssmuth17} Although patients clinically present with severe proximal muscle weakness, less than 30% of patients with mechanical ventilation present protein elevation. This may be because patients were admitted early (median 5 days), as it is well-known that protein elevation is present in 90% of patients at 3 weeks since symptom onset. ^{Reference López-Hernández, Colunga-Lozano and Garcia-Trejo3}

Prolonged mechanical ventilation increases mortality and complications (pressure ulcers, infections, neuropathy, and critically ill myopathy, etc.). ^{Reference De Jonghe, Lacherade and Durand18} The definition varies in the literature. Some authors consider from 5 days to 21 days (19). In GBS, some authors consider prolonged mechanical ventilation as >2 months. However, most authors consider it in >14 days, as we did. ^{Reference Walgaard, Lingsma and Ruts5,Reference van den Berg, Storm, Garssen, Blomkwist-Markens and Jacobs20} A study reported that older age is a risk factor for prolonged mechanical ventilation >21 days. (21) In our study, we observed that age > 60 years is not associated with prolonged mechanical ventilation. ^{Reference Walgaard, Lingsma and Ruts5} Severe impairment of muscle strength, measured by the MRC sumscore is a risk factor for the mechanical ventilation. ^{Reference Shang, Zhu and Baker6} In our population, we observed that severely affected patients with zero points on the MRC score at admission are at risk for prolonged mechanical ventilation. Fourrier et al analyzed 40 patients with GBS and observed that patients who could not dorsiflex the foot at the end of immunotherapy were at risk for prolonged mechanical ventilation >15 days. ^{Reference Fourrier, Robriquet, Hurtevent and Spagnolo22} Walgaard et al reported that severe decrease in strength (≤2 points) in some muscles (deltoid, biceps, extensor carpi, iliopsoas, quadriceps, and tibialis anterior) measured 1 week after admission were also risk factors for prolonged mechanical ventilation ≥14 days. ^{Reference Walgaard, Lingsma and Ruts5} From our consideration, the neuromuscular physical examination in ventilated patients with several days of hospitalization may be influenced by conditions typical of critically ill patients (delirium, hydro-metabolic alterations, sedation effects) that may alter an appropriate assessment. ^{Reference Huang, Huang and Li23}

Nerve conduction studies are very important as they establish the primary mechanism of peripheral nerve damage (demyelinating or axonal). ^{Reference López-Hernández, Galnares-Olalde and Gutiérrez2} In some patients who undergo the very early studies (≤3 days of evolution within symptom onset), a second study is suggested because 20% of patients with AIDP fulfill criteria for axonal variants afterwards. ^{Reference Berciano, Orizaola and Gallardo24,Reference Uncini, Manzoli and Notturno25} For patients with mechanical ventilation, we consider that the initial study is the most important as subsequent neurophysiological studies may be altered due to medication (use of sedatives or muscle relaxants), hydroelectrolytic disturbances, and overlap with critically ill neuropathy and myopathy.

AMAN has a worse functional outcome compared to AIDP, and a previous study in our country reported a higher frequency of mechanical ventilation in axonal variants. ^{Reference Galnares-Olalde, López-Hernández and García-Grimshaw1,Reference Michel-Chávez, Chiquete and Gulías-Herrero26} In our study, we did not observe differences between the electrophysiological variants requiring prolonged mechanical ventilation. Severe axonal damage (distal CMAP ≤1.0 mV) is associated with a worse outcome. ^{Reference Fletcher, Lawn, Wolter and Wijdicks16,Reference López-Hernández, Galnares-Olalde and Jorge de Saráchaga27}

However, the presence of distal CMAP ≤1.0 mV in motor nerve recordings may be due to several factors. In the AMAN variant, it may be due to length-dependent conduction failure because of severe damage in proximal portions of the nerve (undergoing Wallerian-like degeneration), and in the case of the demyelinating variant, it may be due to distal conduction blocks. ^{Reference Uncini and Kuwabara28}

Prior to this study, no electrophysiological risk factors were published associated with prolonged mechanical ventilation. Interestingly, we observed that patients with prolonged mechanical ventilation present severe axonal damage in the motor nerves of the upper extremities (median and ulnar), but not in the motor nerves of the lower extremities (tibial and peroneal), resulting in the multivariate analysis that the severe axonal damage of the median nerve is an independent risk factor for prolonged IMV.

In GBS, both the peripheral nerve and nerve roots are damage by the immune response, including cervical (some form the brachial plexus), thoracic, and lumbar roots. In the case of patients with GBS with prolongated ventilation, an important factor is diaphragmatic weakness due to damage to the phrenic nerves that exit the cervical roots C3-C4-C5; however, nerve conduction studies of the phrenic nerve are not technically easy to obtain and, in most hospitals, do not have adequate technical equipment. ^{Reference Knutsen and Calfee29-Reference Shang, Zhu, Baker, Feng, Zhou and Zhang31} Based on the above, researchers have reported valuable clinical observations, Walgaard et al., observed that the decrease in the strength of the deltoid muscle was considered a risk factor for prolonged ventilation, as it represents an indirect data on the affection of the C5 root which is also part of the phrenic nerve. ^{Reference Walgaard, Lingsma and Ruts5} Following the concept of cervical root involvement and association with prolonged IMV, we observed that severe damage of the median nerve (C8-T1 roots) is an independent risk factor for prolonged mechanical ventilation in patients with GBS. We theorize severe damage to the median nerve may be a “window” to assess the severity of damage to the cervical roots. Other nerve conduction studies are used to assess nerve roots such as F-wave measurement, but this is not valuable when distal CMAP are severely diminished. ^{Reference Uncini and Kuwabara9}