Comparative or Combination Interventions

There are limited studies examining combinations of interventions for the improvement of respiratory function post SCI. However, of those that meet the SCIRE inclusion criteria, the primary focus is on the type of ventilation received by patients: multiple, singular, or none.

Discussion

The systematic review of Berney et al. (2011) assessed 21 studies and showed reduction in mortality, respiratory complications, and need for tracheostomy when an acute SCI respiratory protocol with a combination of treatment techniques was followed. Authors cautioned that further studies using specific interventions and more rigorous research designs were required.

A case control study by Watt et al. (2011) determined that patients who used diaphragm pacing with MV compared to those who only had MV had significantly higher survival rates. Of those patients between the ages of 31-35 years, those who were weaned from a ventilator before discharge experienced higher rates of survival compared to those that were not weaned from a ventilator before discharge (Watt et al. 2011). Duarte et al. (2021) showed that total INV duration, overall length of stay (LOS), and LOS in intensive care unit (ICU) were shorter in patients who received transcutaneous electrical diaphragmatic stimulation (TEDS), combined with a standard weaning protocol.

With respect to other respiratory parameters, when comparing endotracheal invasive ventilation (EIV) with transtracheal open ventilation (TOV), there were no significant differences in partial pressure of oxygen between the two treatment types, although patients did have a significantly lower partial pressure of carbon dioxide with EIV (Gregoretti et al. 2005).

Romero-Ganuza et al. (2011b) examined timing, type, and presence of tracheostomies in patients with acute SCI. Of those who received an ET there were fewer cases of tracheal stenosis compared to late tracheostomy (LT). The type of tracheostomy that patients received also resulted in significant differences, where patients who had a percutaneous tracheostomy experienced fewer cases of pneumonia compared to ST.

Methylxanthines such as theophylline have been used in respiratory dysfunction since the 1920s (Schultze-Werninghaus & Meier-Sydow 1982); and the earliest published use of methylxanthines for respiratory dysfunction in SCI was about 40 years later (Segal et al. 1986). Theophylline has three primary modes of action in the treatment of pulmonary dysfunction including bronchodilation, anti-inflammation and improved diaphragmatic contractility (Zakrasek et al. 2017); and specifically, in cervical SCI, theophylline has an additional proposed mechanism of improving pulmonary function, namely activation of a latent crossed phrenic pathway by adenosine receptor antagonism (Nantwi & Goshgarian 2005). Zakrasek et al. (2017) found a strong correlation of ventilator liberation in the first 24 hours with level of injury (C3-C5) and a moderate correlation with gender and age when theophylline was added as an experimental variable (though six participants had adverse events with the drug).

Kaufman et al. (2022) prospectively studied a treatment protocol using a surgical algorithm involving diaphragm pacing, phrenic nerve reconstruction, and diaphragm muscle replacement. They analyzed 10 ventilator dependent cervical ASIA A patients, who received different treatments based on the extent of neuromuscular dysfunction (pacemaker alone, pacemaker + phrenic nerve reconstruction or pacemaker + diaphragm muscle replacement), showing four patients who achieved a partial weaning and four a complete weaning (CW).

Korupolu et al. (2021) retrospectively analyzed 84 patients with acute SCI receiving MV with a tracheostomy if they underwent moderate Vt (<15ml/kg PBW) or higher Vt (>15ml/kg PBW) during their stay in an inpatient rehabilitation facility. Overall, 87% of patients were successfully weaned off MV with no significant difference between groups. On the other hand, they showed that the HVt group had increased incidence and the risk of pneumonia and other adverse events compared to the MVt group. More precisely, for every 1 ml/kg PBW increment in Vt, risk of pneumonia increased by 28% and odds of the composite outcome of developing any pulmonary adverse events increased by 42%. In the same way, Hatton et al. (2021) retrospectively analyzed 181 patients with acute SCI receiving ventilation if they underwent standard Vt (< 10 cc/kg PBW) or HVtV (> 10 cc/kg PBW) during their stay in a level 1 trauma center. While hospital-free days and vent-free days were similar between groups, patients who received HVtV were more likely to develop VAP and require a tracheostomy than those who received standard Vt. Both Hatton et al. ( 2021) and Korupolu et al. (2021) highlighted that these were the first studies to investigate the association between tidal volumes on rates of VAP, pneumonia, and other undesirable respiratory outcomes in an acute inpatient as primary outcomes, reporting findings contrary to the accepted guidelines for ventilator weaning in SCI.

Conclusion

There is level 2 evidence (from one prospective controlled trial: Gregoretti et al. 2005) that EIV may lower partial pressure of carbon dioxide compared to TOV in patients with acute SCI.

There is level 3 evidence (from one case control study: Watt et al. 2011) that diaphragm pacing in combination with MV may result in higher survival than MV alone in acute SCI populations.

There is level 4 evidence (from one retrospective case series: Duarte et al. 2021) that implementation of TEDS combined with standard weaning protocol shortened the time of IMV, overall stay LOS and ICU LOS compared to the implementation of standard weaning protocol alone in tracheostomized SCI participants.

There is level 3 evidence (from one case control study: Romero-Ganuza et al. 2011b) that percutaneous tracheostomies may result in fewer cases of pneumonia compared to surgical tracheostomies in people with acute SCI.

There is level 3 evidence (from one case control study: Korupolu et al. 2021) that administration of high Vt (> 15ml/kg PBW) increased incidence and the risk of pneumonia and pulmonary adverse events compared to administration of moderate Vt (< 15ml/kg PBW), during MV in tracheostomized participants.

There is level 3 evidence (from one case control study: Hatton et al. 2021) that administration of high Vt (> 10 cc/kg PBW) increased the risk of ventilator-associated pneumonia (VAP) compared to administration of standard Vt (< 10 cc/kg PBW), during MV in patients with acute cervical SCI.

There is level 3 evidence (from one retrospective analysis: Zakrasek et al. 2017) that the implementation of specialized respiratory management (HVtV, HFPV, MIE) provided high rates of ventilator weaning (100% for C4 and C5 AIS-A,B, 91 % C3 AIS-A,B).

There is level 4 evidence (from one pre-post study: Kaufman et al. 2022) that the implementation of a treatment protocol which included a surgical algorithm that involved diaphragm pacing, phrenic nerve reconstruction, and diaphragm muscle replacement provided a rate of 80% of successful weaning (40% partial weaning and 80% CW) in patients with ventilator-dependent cervical tetraplegia and ASIA A.