Guillain–Barré syndrome (GBS) is an acute inflammatory polyneuropathy due to an autoimmune response directed against peripheral nerve antigens.1 The incidence of GBS have found rates to be between 0.16 and 4.0/100,000/year in individuals of all ages, with the highest rates been reported in adults, especially those aged over 75 years. While more than half of cases are clinically “mild,” many patients develop complications which can led to substantial morbidity and mortality.2 Respiratory failure remains the most serious complication of GBS and occurs in up to one third of the patients.3 Unfortunately, the onset of respiratory insufficiency is often insidious and late or urgent intubations are associated with increased risk of complications and prolonged hospitalization.4 Thus, early identification of GBS subjects at high risk of respiratory failure is important to implement adequate monitoring and rapidly provide respiratory support when clinically indicated.

Prior studies had identified risk factors for invasive mechanical ventilation, such as presenting to the hospital <7 days from the time of onset of symptoms, inability to lift the elbow, presence of bulbar involvement, grade of disability on admission, or descending weakness.5–8 However, these studies did not included patients requiring non-invasive support, an increasingly common ventilatory mode. Pulmonary function test findings, such as a reduction in the vital capacity and maximal inspiratory or expiratory pressures are also recognized risk factors for impending respiratory failure.6 Nevertheless, spirometry, or pressure transducers, are not routinely available, the presence of facial weakness may influence the results, and the procedures may lead to delays in initiating ventilatory support.

In this study, we analyzed data from a cohort of subjects hospitalized due to GBS to identify early clinical risk factors, present at the time of admission, for respiratory failure requiring invasive or non-invasive ventilatory support.

During the study period, 113 potentially eligible participants were admitted to the neurological center. No patient met any of the exclusion criteria. The mean (range) age of the study population was 47 (25–76) years and 55% were male. A trigger event was reported by 76 (67%) subjects, most commonly upper respiratory tract infections (35%) and diarrhea (25%). The median (range) time from onset of weakness to hospital admission was 8 (0–31) days. (Table 1).

Overall, 12% (13/113) subjects developed respiratory failure (69% required invasive ventilation), at a mean (range) time of 21–7 days from hospital admission (Fig. 1). No other patient developed respiratory failure in the first month. In unadjusted analyses, there were no differences between the groups in the distribution of age, sex, presence of comorbidities, sensory abnormalities, or complementary studies (p>0.05 for all comparisons; Table 1). Presence of any cranial nerve involvement (OR: 14.7, 95% CI: 1.8–117.1), facial palsy (OR: 17.3, 95% CI: 2.2–138.0), and bulbar weakness (OR: 10.7, 95% CI: 2.3–50.0) were significantly associated with increased risk of respiratory failure. Lower MRC sum scores (41–50 score OR: 2.12, 95% CI: 0.53–8.46; 31–40 score OR: 3.11, 95% CI: 0.49–19.54; and <30 score OR: 14.0, 95% CI: 1.54–127.2 compare with a score >50) were also associated with increased risk of respiratory failure. Similarly, subjects with lower neck MRC scores (4 score OR: 2.8, 95% CI: 0.5–15.1 and <3 score OR: 21.0, 95% CI: 3.5–125.2 compare to a score of 5) had higher odds of respiratory failure (Table 2).

Figure 1.

Cumulative risk of respiratory failure in Guillain–Barre patients at 28 days of admission.

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Adjusted analyses showed that presence of bulbar weakness (OR: 7.6, 95% CI: 1.3–43.0) and low-neck MRC scores (<3 score OR: 9.2, 95% CI: 3.5–125.2 vs. score >3) were independently associated with increased risk of respiratory failure.

Our study shows that, in patients with GBS, respiratory failure may be predicted by simple clinical markers. In our patients, bulbar or neck weakness at admission, two clinical predictors that are evaluated as part of the routine physical exam, were independently and strongly associated with subsequent need for ventilatory support. These physical exam findings could be used to guide decisions about early ICU admission and/or respiratory monitoring.

Assessment of ventilatory status and making decisions regarding the need for ventilatory support are major aspects of the management of hospitalized GBS patients. Prior studies have evaluated potential risk factors for respiratory failure in this population. Muscular strength, including head, elbow, and foot is a frequently identified risk for the need of ventilatory support.5,8,12 These strength test support ours results, and we provide a numerical cutoff (MRC scale) to be as objective as possible. Similarly, Lawn et al., in a study including 114 patients with GBS, showed that involvement of cranial nerves, particularly the facial nerve, is more common among patients who later develop respiratory failure.6 In our study cranial nerve involvement was associated with increased risk of respiratory failure. However, when it was adjusted for cofounders, it was not an independent risk. Other studies reported that a shorter time between onset of weakness to hospitalization was associated with respiratory failure,13 particularly among patients with more extensive muscular weakness.12,14,15 We did not find any association with the time of weakness.

Baseline spirometry (at time of admission) may also help identify high risk patients with serial measures used to monitor progression and make decisions regarding the need for invasive or non-invasive ventilation.6 However, these studies defined respiratory failure as the need for invasive ventilation. Our study extends these results by showing that two clinical parameters (bulbar and neck weakness) easily obtained during baseline examination are strongly associated with the risk of respiratory failure, including both invasive and non-invasive ventilatory support. Moreover, we used a validated measure with clearly pre-established cutoffs, which could facilitate implementation of these findings into clinical practice.

Several mechanisms may explain the association between bulbar weakness and respiratory failure in hospitalized patients with GBS. First, bulbar weakness leads to inability of protecting the airway and difficulties clearing secretions. Second, muscular bulbar involvement induces upper airway collapse, rising airway resistance, work of breathing and respiratory muscle load, promoting fatigue, and ultimately respiratory failure. A functional and undamaged cervical plexus is needed to counterbalance gravity and maintain the head upright. Neck muscles are controlled by nerves arising from the deep cervical plexus (C2–C5) while the phrenic nerve supplying the diaphragm originates from the deep cervical roots C3–C5. Thus, neck weakness is likely a marker for diaphragmatic muscle compromise providing physiologic plausibility to our observed associations. Additionally, neck weakness may also contribute to swallowing impairment and increased risk of aspiration because proper neck posture promotes successful swallowing.

The study has strengths and limitations that are worth discussing. Unlike previous studies that focused on more severe patients, this study uses a broader study population (regardless of their severity), that allowed us to identify a more conservative 12% incidence of respiratory failure, compared to the 30–50% reported in other series, that were limited to patients with more severe disease. This may better represent the overall population of GBS patients.

Our study has clear limitations, which are linked mainly to its retrospective and monocentric design, consequently the results may not be generalizable to other settings. We retrospectively analyzed data collected as part of a GBS registry. However, predictors were captured at admission and thus, reviewers were not aware of the study outcomes (i.e., subsequent respiratory failure). Moreover, data capture was standardized to avoid biases in the assessment of risk factors for respiratory failure. Our study had a relatively small sample size which limited the number of predictors that we were able to evaluate in adjusted analyses and generated relatively high uncertainty (i.e., large CI) in the estimation of the ORs. However, GBS is a relatively rare disease and our sample size is amongst the largest reported in studies of this condition.

In summary, our study showed that bulbar and neck weakness at the time of admission can be used to identify GBS subjects at high risk of respiratory failure. These are relatively easy to measure clinical variables that could guide decisions about the level of monitoring and/or placement of GBS patients into the ICU or similar settings.

Authors received no financial support for this study. Dr. Wisnivesky received consulting honorarium from Sanofi, Glaxosmithkline and Bannok and research grants from Sanofi and Quorum.

Authorship requirements have been met: LPM conceived and designed the study, collected, interpreted, and analyzed data, searched literature, and wrote the manuscript; JPW designed the study, interpreted, and analyzed data, and wrote the manuscript; MW and FRL conceived the study, collected data, searched literature, and critically revised the manuscript; FAV and NAW conceived the study and critically revised the manuscript.

All other authors have no conflict of interests to declare.