Submitted:
24 October 2023
Posted:
25 October 2023
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Abstract
Keywords: Post-Stroke; Hyperbaric oxygen therapy; Sequelae; Feasibility; Out-patient.
Keywords:
post-stroke
; hyperbaric oxygen therapy
; sequelae
; feasibility
; out-patient
1. Introduction
HBOT is a well-known treatment in many as listed by the European Committee for Hyperbaric Medicine [1] In recent time much have been discovered regarding its mode of action. From High oxygen flow improving oxygen delivery to hypoxic tissues, we know that its action is mainly dependent of the free oxygen radicals that are produced. These free oxygen radicals have a great impact on cellular processes, transcription factors, mitochondrial function, oxidative stress, and inflammation [2].
Lately, HBO has been proposed for the treatment of chronic stroke [3]. In Switzerland, we have only two hyperbaric facilities functioning in accordance with the European Code of Good Practice of Hyperbaric Oxygen Therapy [4]. The aim of the present study was to assess the feasibility of HBOT in daily practice for highly motivated ambulant patients after they had had intensive and comprehensive rehabilitation program and were interested in innovative means to further increase their neurological impairments. We wanted also to know if these patients were able and enough motivated to travel daily from another city, traveling distance up to 110 Km.
2. Materials and Methods
After approval by of the local ethical committee (EKNZ, Nr. 2017-02131), patients with stroke sequelae who had completed a standardized in-hospital stroke rehabilitation program. Patients were asked if they were interested in participating in HBOT as an additional therapeutic approach. All patients who met the inclusion and exclusion criteria were included in the study. After a successful pressure test, patients signed an informed consent form. Some patients had to travel from another city to be treated in our outpatient center. Recruitment (2018-2021) was stopped when 10 patients successfully completed HBOT as foreseen.
Table 1.
Inclusion/Exclusion criteria.
| Inclusion | Exclusion |
| Ischemic stroke with residual defects | Inability to understand the informed consent form |
| Conclusive brain CT or brain MRI | Inability to put on a face mask |
| Uneventful pressure test 0,5 ATA | Claustrophobia |
| Uncontrolled epilepsy | |
| Dementia or psychological disorder | |
| Previous pneumothorax | |
| Positive pregnancy test | |
| Anticonception measures during HBO | |
| Unsuccessful pressure test 0,5 ATA |
All patients were treated in our multiplace chamber to a pressure of 2.0 ATA according to the European Code of Good Practice. One treatment lasted 2 hours with 90 minutes of oxygen, 5-minutes air brake after 45 minutes as a prevention against neurological toxicity due to high-pressure oxygen inhalation. Oxygen was provided with a tight face mask.
Potential visual side effects were assessed using the Snellen chart, before, immediately after 40 HBO and 3 months later. Possible Ear Nose Throat side effects were assessed with an interview and a digital otoscopy before and after each single HBO treatment.
Base line neurological assessment was done with NIHSS and was repeated after 40 sessions as well as three months later. It was done by a trained neurological physician. A further neurological assessment was done by the hyperbaric physician using a Rivermead mobility index (RMI) before the start of HBO, then weekly and again 3 months later. Patients’ compliance was daily assessed with an attendance list filled by the hyperbaric technician.
The levels of stroke severity as measured by the NIHS scoring system were:
- 01–04 = minor stroke
- 5–15 = moderate stroke
- 15–20 = moderate/severe stroke
- 21–42 = severe stroke
3. Results
Our patients had a mean age of 61 years, 1 female, 12 men and the mean time from Stroke to the start of HBOT was 43 months. The mean age of the patients who fulfilled the entire program was 60 years and the mean time from stroke to the start of HBOT was 52 months, 31 months if we exclude patient 2.
3.1. Neurology
8 of the 10 patients who completed the study showed some improvement with HBO in the NIHS scale, in 2 patients there was no effect. There was no improvement in self-reported RMI.
Table 2.
Effect of 40 sessions HBO at 2.0 ATA in rehabilitated post-stroke patients.
| Patient # and (age) | Time to stroke in months |
NIHSS Before HBOT |
NIHSS 3 months after HBOT |
RMI before HBOT | RMI after 10 HBOT |
RMI after 20 HBOT |
RMI after 30 HBOT |
RMI after 40 HBOT |
RMI 3 months after HBOT |
|---|---|---|---|---|---|---|---|---|---|
| 1 (57) | 65 | 4 | 3 | 14 | 14 | 14 | 14 | 14 | 14 |
| 2 (86) | 251 | 3 | 2 | 13 | 14 | 14 | 14 | 14 | 14 |
| 3 (63) | 60 | 5 | 2 | 15 | 14 | 15 | 15 | 15 | 15 |
| 4 (69) | 14 | 8 | 8 | 9 | 9 | 6 | 8 | - | 8 |
| 5 (58) | 4 | 3 | Withdraw | ||||||
| 6 (75) | 12 | 4 | 4 | 12 | 13 | 13 | 13 | 15 | 15 |
| 7 (60) | 19 | withdraw | |||||||
| 8 (69) | 7 | 6 | withdraw | ||||||
| 9 (65) | 18 | 4 | 3 | 19 | 14 | 15 | 15 | 15 | 15 |
| 10 (35) | 47 | 6 | 2 | 15 | 15 | 15 | 15 | 15 | 15 |
| 11 (66) | 15 | 3 | 2 | 13 | 13 | 13 | 14 | 14 | 14 |
| 12 (57) | 21 | 3 | 2 | 15 | 15 | 15 | 15 | 15 | 15 |
| 13 (34) | 17 | 4 | 3 | 15 | 15 | 15 | 15 | 15 | 15 |
Table 3.
Details of NIHSS changes.
| Patient | Changes of NIHSS score 3 months after 40 HBOT | Patients reporting |
| 1 |
4 ↗ 3 facial palsy ↔ with 1 left arm motricity ↗ from 2 to 1 left leg motricity ↔ with 1 |
Less fatigue, improved supination, |
| 2 |
3 ↗ 2 ataxia extremities ↔ with 2 dysarthria improved from 1 to 0 |
Psychological state very good, left arm better, walking unchanged |
| 3 | 5 ↗ 2 facial palsy ↔ with 1 motricity right leg ↔ with 1 ataxia right leg improved ↗ from 2 to 0 sensibility ↗ from1 to 0. |
Does not know if it was helpful, sensibility clearly better |
| 4 |
8 ↔ 8 orientation ↔ with 1 visual field ↔ with 2 motricity ↔ with 1 ataxia ↗ from 1 to 0 sensibility ↘ from 0 to 1 language ↔ with 1 dysarthria ↔ with 1 neglect ↔ with 1 |
|
| 6 |
4 ↔ 4 motricity left leg ↔ with 1 ataxia left ↔ with 2 sensibility left ↔ with 1 |
Patient feels he can walk better |
| 9 |
4 ↗ 3 facial paresis ↗ from 1 minimal to 0 motricity right leg ↔ with 1 ataxia right ↔ with 1 dysarthria ↗ from 1 light to 0 |
|
| 10 |
6 ↗ 2 compliance with order improved from 1 to 0 motricity right leg and arm ↗ from 1 to 0 |
Clear improvement, still improving, does not know if it is due to HBO |
| 11 |
E ↗ 2 ↔ motricity right leg with 1 ataxia right leg ↗ from 2 to 1 |
Found treatment very good and felt that his right leg had improved |
| 12 |
3 ↗ 2 motricity right leg ↗ from 1 to 0 ataxia right leg ↗ from 1 to 0 |
The patient sees no effect of HBO, function of the hand is a bit improving but it cannot be objectivated with the NIHSS score. Handwriting slightly improved |
| 13 |
4 ↗ 3 motricity right Arm ↗ from 1 to 0. |
No effect on tiredness, right arm feels heavy but does not sink anymore when held in horizontal position |
↔ = unchanged, ↗ = improved, ↘ = worse.
There were no signs of acute oxygen brain toxicity.
3.2. Visual acuity
We could not detect a shift towards myopia in our patients.
Table 4.
Visual side effects of hyperbaric oxygen at 2.0 ATA in Stroke patients.
| Patient | Glasses | Snellen chart before HBOT | Snellen chart after 40 HBOT | Snellen chart 3 months after HBOT | |||
| Left | Right | Left | Right | Left | Right | ||
| 1 | Yes | 1.08 | 0.96 | 1.08 | 0.96 | 0.96 | 0.84 |
| No | 0.12 | 0.12 | 0.12 | 0.12 | 0.12 | 0.12 | |
| 2 | Yes | 0.84 | 1.2 | 0.9 | 1.0 | 0.84 | 1.2 |
| No | 0.36 | 0.24 | 0.5 | 0.6 | 0.48 | 0.48 | |
| 3 | Yes | - | - | - | - | - | - |
| No | 0.8 | 0.8 | 0.8 | 0.9 | 0.8 | 0.9 | |
| 4 | Yes | - | - | - | - | - | - |
| No | 0.96 | 0.96 | 0.84 | 0.72 | 0.84 | 0.72 | |
| 6 | Yes | 0.36 | 0.48 | 0.72 | 0.72 | 0.7 | 0.7 |
| No | 0.24 | 0.36 | 0.24 | 0.24 | 0.5 | 0.5 | |
| 9 | Yes | 0.96 | 0.72 | 1.08 | 0.72 | 0.96 | 0.72 |
| No | <0.1 | <0.1 | <0.1 | <0.1 | 0.12 | 0.12 | |
| 10 | Yes | 0.6 | 1.08 | 0.6 | 0.84 | 0.6 | 1.08 |
| No | 0.36 | 0.72 | 0.36 | 0.8 | 0.36 | 0.72 | |
| 11 | Yes | - | - | - | - | - | - |
| No | 0.96 | 1.2 | 0.84 | 1.2 | 0.96 | 1.2 | |
| 12 | Yes | - | - | - | - | - | - |
| No | 0.84 | 0.6 | o.84 | 1.2 | 1.2 | 1.2 | |
| 13 | Yes | - | - | - | - | - | - |
| No | 0.96 | 1.2 | 0.84 | 0.84 | 0.8 | 1.0 | |
3.3. Pressure related effect
Patient Number 10 had difficulties in equalizing and had to pause HBOT, he resumed HBOT after one week and fulfilled the program as scheduled. In this case digital otoscopy showed a transitory barotrauma of the eardrum staged as Teed 2 which had normalized after one week.
3.4. Compliance
13 patients were recruited.
Patient Number 5 was examined by the neurologist and started HBO as scheduled but after 5 sessions commuting to our center had become too time consuming for him, therefore he decided to withdraw from the study.
Patient Number 7 and 8 signed the informed consent. Patient 7 did not show up to first neurological examination, patient 8 was examined by the neurologist but never showed up to HBO.
In total, 10 out of 11 patients who started HBOT completed 40 HBOT as prescribed.
4. Discussion
Our study confirms that 40 HBOT are well tolerated in unselected patients with mild to moderate post-stroke residual symptoms. All patients except two patients (patient 4, 6) had an improvement of their neurological symptoms according to NIHSS but not according to RMI. This is probably because our patients suffered only from mild stroke and were therefore not suited for RMI.
We did not select our post-stroke patients and had no advanced imaging information regarding their potential of neuroplasticity and were surprised by the relatively high rate of positive response to HBOT. Even without a control group, we attributed the improvement as a HBOT effect. It is well known that spontaneous improvements can occur in some stroke patients after one or two years. However, in our sample this was the case in 8 of 10 patients [5].
Rosario et al [6] as well as Schiavo et al. [7] had similar results regarding the feasibility of HBOT at 2.0 ATA in their prospective series on unselected post stroke patients. They also found that these patients were strongly motivated to collaborate with the physicians in a hyperbaric center dedicated to outpatients. Churchill et al. [8] came to the same conclusion with a protocol involving 60 consecutive sessions. They noted that even 6 months after HBO, 90% of their patients were willing to repeat HBO.
Several researchers have pointed out the plasticity potential of the post stroke brain. They could show that there is a penumbra of dormant neurons around the stroke area and that it can regain some functionality after HBOT. This has been demonstrated with PET scans [9] and more recently with diverse technology using functional MRI [10].
In a first study, Efrati et al. found that HBOT [3] can improve neuroplasticity in post-stroke patients. Later [11] they suggested that the existence of a large penumbra could be an indicator of responsiveness to HBOT.
According to the literature up to 57% of HBOT induced myopia can be expected using compression rates of 2.2-2.5 ATA. [12]. Using 1.5 ATA, Churchill et al. found only 3 out of 55 patients with a myopic shift [8]. In our small study with 2.0 ATA, we did not find any case of such myopia, maybe because we treated only 10 patients.
5. Conclusion
Extensive HBOT treatments in post-stroke patients are feasible in an outpatient setting with minor and reversible side effects, even if patients must commute daily to the hyperbaric facility. HBOT seems to have the potential to improve their clinical state. However, there is an urgent need to select potential responders with imaging techniques and better assess the role of HBOT. This can only be done with prospective controlled studies.
Author Contributions
Conceptualization, M.G, J.S. and S.E.; methodology M.G, J.S.; validation M.G, J.S. and S.E.; formal analysis J.S.; investigation M.G, J.S. P.S. N.P and S.E.; resources M.G, J.S. and S.E.; writing-original draft preparation J.S.; writing—review and editing M.G. and S.E.; supervision M.G.; project administration, M.G.; funding acquisition, J.S. and M.G.
Funding
Funding was provided by Carbagas company who offered oxygen necessary for the study, Vifor company provided CHF 1’000.—Electricity for the hyperbaric chamber, maintenance, liability insurance was all provided by M.G.
Institutional Review Board Statement
The study was conducted in accordance with the Declaration of Helsinki and approved by the Ethics Committee Ethikkommission Nordwest- und Zentralschweiz, project ID 2017-02131, dated 24.1.2018.
Informed Consent Statement
Informed consent was obtained from all subjects involved in the study. Written informed consent has been obtained from the patient(s) to publish this paper.
Data Availability Statement
available in section “MDPI Research Data Policies” at https://www.mdpi.com/ethics.
Acknowledgments
To the medical staff of the Hyperbaric Center Basel and Mrs. Vivianne Hasselmann for her help for study monitoring.
Conflicts of Interest
M.G. is head of Hyperbaric Center Basel, J.S. was founder of the of Hyperbaric Center Basel. Both are involved in daily hyperbaric treatments.
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