Abstract

Background

Hyperbaric oxygen (HBO) has been used to treat many diseases. However, there are few reports on HBO treatment of paroxysmal sympathetic hyperactivity (PSH) at home and abroad, and the clinical experience is very limited. The purpose of this study is to explore the efficacy of HBO treatment on PSH.

Methods

This multicenter, retrospective study was conducted in central China. 56 PSH patients who underwent HBO treatment from January 2021 to September 2023 were selected as the HBO group from five hospitals in central China that carried out HBO business. In addition, 36 PSH patients who did not undergo HBO treatment from May 2018 to December 2020 in Zhengzhou People ‘s Hospital were selected as the control group. The HBO group and the control group, before and after HBO treatment were compared and analyzed from two aspects of PSH Assessment Measure ( PSH-AM ) and Glasgow Coma Scale ( GCS ) to evaluate the effect of HBO treatment on PSH efficacy and prognosis of patients.

Results

Compared with before HBO treatment, after 3 courses of HBO treatment, the PSH symptoms of all patients were significantly relieved ( Hyperthermia ( 36 ( 64.29 ) VS 8 ( 14.29 ), P = 0.001 ), Tachycardia ( 55 ( 98.21 ) VS 14 ( 25.00 ), P = 0.020 ), Tachypnea ( 43 ( 76.79 ) VS 8 ( 14.29 ), P = 0.001 ), Hypertension ( 48 ( 85.71 ) VS 5 ( 8.93 ), P < 0.001 ), Sweating ( 48 ( 85.71 ) VS 6 ( 10.71 ), P = 0.010 ), Posture ( 42 ( 75.00 ) VS 11 ( 19.64 ), P = 0.001 ) ) ; GSC score improved ( 5.95 ± 2.18 VS 12.31 ± 5.34, P < 0.001 ), PSH-AM (CFS+DLT) score decreased significantly ( 22.12 ± 3.12 VS 16.90 ± 4.81, P < 0.001 ). At 30 days of hospitalization, PSH symptoms were significantly improved in the HBO group compared to the control group ( Hyperthermia ( 8 ( 14.29 ) VS 7 ( 19.44 ), P = 0.058 ), Tachycardia ( 11 ( 19.64 ) VS 9 ( 25.00 ), P = 0.048 ), Tachypnea ( 6 ( 10.71 ) VS 10 ( 27.78 ), P = 0.035 ), Hypertension ( 4 ( 7.14 ) VS 8 ( 22.22 ), P < 0.036 ), Sweating ( 5 ( 8.93 ) VS 9 ( 25.00 ), P = 0.036 ), Posture ( 11 ( 19.64 ) VS 14 ( 38.89 ), P = 0.043 ) ) ; GSC score was higher ( 14.12 ± 4.12 VS 12.31 ± 4.14, P = 0.002 ), PSH-AM (CFS+DLT) score was lower ( 16.9 ± 3.81 VS 19.98 ± 4.89, P = 0.010 ), intensive care unit ( ICU ) hospitalization time was shortened(18.01±5.67 VS 24.93±8.33 , P = 0.001).

Conclusion

The use of HBO therapy at the same time as the treatment of the primary disease can significantly alleviate the symptoms of PSH patients, therapeutic results are better, and provides new ideas for the treatment for PSH patients.

Keywords: Hyperbaric oxygen; Paroxysmal sympathetic hyperactivity; Brain injury

Authors:

Yujing Li
Songying Shen
Xin Li
Changhe Li
Yihao Li
Huimin Chen
Caihong Re
Yinsen Song
Huijun Dong
Meng Zhao
Sisen Zhang
Hongyu Wang

Correspondence:

Hongyu Wang
People’s Hospital of Henan University of Chinese Medicine/People’s Hospital of Zhengzhou
33 Huanghe Road, Jinshui District, Zhengzhou City, Henan Province, China
Tel:+86-13674950311
Fax:+86 67078340
Email: [email protected]

Background

Paroxysmal sympathetic hyperactivity syndrome (PSH) is a complication that is not easily detected in clinical practice. It is characterized by abnormal sympathetic excitation after severe brain injury and is also known as acute midbrain syndrome, autonomic dysfunction syndrome, and muscle contraction-related hyperthermia. The naming and diagnostic criteria of PSH were not standardized until the 2014 international consensus[1]. That is, PSH is a group of relatively severe autonomic nervous system disorder syndromes with symptoms including periodic episodes of hyperthermia, hypertension, tachycardia, tachypnea, sweating, and posturing such as dystonia, hypertonia, or spasticity[1]. It often appears after craniocerebral injurious disorders, with craniocerebral trauma being the most common[2–5]. PSH is rare and easily overlooked and underdiagnosed in clinical practice [6]. Most of the available literature consists of case reports[7–9]. Currently, clinical treatments for PSH are limited and mostly symptomatic and supportive[10,11].

Hyperbaric medicine is the branch of medical science that studies the physiological and pathophysiological changes in organisms when they are subjected to higher atmospheric pressures. Hyperbaric oxygen（HBO） therapy is a method of breathing pure or highly concentrated oxygen in a pressurized environment to treat hypoxic and related diseases[12]. HBO therapy is based on the elevation of PaO2 in the blood when oxygen is breathed in a hyperbaric chamber at a pressure higher than atmospheric pressure, and the mechanism can be explained by the Boyle-Marriott law of volume effect and Henry’s law of solubility[13]. Through clinical practice, HBO therapy has an irreplaceable role for certain diseases and has gradually become one of the main means of comprehensive clinical treatment of certain diseases[14]. At present, HBO therapy is widely used. In the treatment of carbon monoxide poisoning[15], hypoxic coronary heart disease[16], craniocerebral trauma[17], tumor[18], neonatal asphyxia[19] and other diseases have achieved good results.

However, there are few reports on the treatment of PSH with HBO at home and abroad. Checking the literature, only Choi reported a case of PSH symptoms after carbon monoxide poisoning in 2021, which was treated with HBO and achieved good therapeutic results[20]. Therefore, we conducted a multicenter retrospective study to summarize the clinical characteristics of patients with PSH who underwent ultra-early HBO treatment, which is reported as follows.

Methods

Patient Enrollment

We conducted a retrospective study in five hospitals in central China where HBO therapy is practiced. PSH cases that underwent HBO treatment from January 2021 to September 2023 in the 4 hospitals were selected as the HBO group, and PSH patients in Zhengzhou People’s Hospital who underwent HBO treatment from May 2018 to December 2020 without HBO treatment were selected as the control group. Inclusion criteria: (1) meeting the diagnostic criteria of PSH; (2) clear etiology of craniocerebral injury; (3) ≥3 courses of HBO therapy. Exclusion criteria: (1) those who were unconscious before the current episode; (2) previous history of craniocerebral injury; (3) hospitalization <20 d; (4) pregnancy; (5) hemodynamic instability. This study received approval from the ethics committees of all participating hospitals. This study was conducted in accordance with the declaration of Helsinki. As a retrospective study, informed consent was waived.

Diagnostic criteria and therapy

PSH was diagnosed using the 2014 internationally recognized diagnostic criteria known as PSH assessment measure (PSH-AM)[1]. It consists of two parts: (1) the clinical feature scale (CFS) to assess the severity of clinical symptoms of PSH (Table 1); (2) the diagnosis likelihood tool (DLT) to confirm the likelihood that the observed symptoms are originated from PSH (Table 1). The PSH-AM score was calculated by summing the two scores. PSH was diagnosed in this study only if the PSH-AM score was ≥17 (Table 1). All the diagnosed patients underwent EEG to differentiate them from epilepsy by clinical symptoms, EEG and response to antiepileptic drugs.

Therapeutic measures: The care bundles for PSH is used[21], including: reducing any stimuli that may trigger a PSH attack to a minimum, mechanical ventilation if necessary, appropriate fluid rehydration, nutritional support to ensure the metabolic needs of the body, and early rehabilitation and exercise. Internal medicine is the main treatment for PSH, which acts to inhibit the output of central sympathetic nerves and block the response of end organs of the sympathetic nervous system. Beta-blockers were applied to reduce basal metabolic rate and circulating catecholamine levels. Continuous pumping with esmolol was used initially and oral metoprolol was started after recovery of gastrointestinal function. Baclofen application was given to patients with tonic spastic state and dystonia. After complete resolution of PSH symptoms, the corresponding drug therapy was continued for 2 weeks, followed by gradual discontinuation.

HBO treatment: Patients in the HBO group were treated with HBO as early as possible. If it was not possible to withdraw from mechanical ventilation, they could be taken off the ventilator after percutaneous tracheotomy at an early stage, and if necessary, they could be carried on the ventilator in the oxygen chamber to be treated with HBO. The time from the onset of the disease to the beginning of HBO treatment for 56 patients was from 3 to 11 d, and the duration of the HBO treatment was from 3 to 5 courses of treatment. The HBO treatment was carried out in the single-compartment oxygen chamber, which was manufactured by the Shanghai Seven hundred and eleven Hyperbaric Oxygen Chamber Co. The oxygen chamber was manufactured by Shanghai 701 Hyperbaric Oxygen Chamber Co., Ltd, model SHC900GD, with a length of 2.6 m, a diameter of 1.3 m, a weight of about 1,500 kg, and a maximum operating pressure of 3.0 standard atmospheres. The pressure was 0.16 Mpa (1.6 ATA), twice a day, each lasting 70 min: 20 min of pressure increase, 30 min of maintenance, and 20 min of pressure decrease; 10 d was 1 course of treatment, and a total of 3 to 5 courses of treatment were performed. During the HBO treatment, the PSH symptom relief was closely observed.

Statistical analysis

Statistical analysis was performed using SPSS 23.0 software. Continuous data were first tested for normality. Normally distributed data were expressed as mean ± standard deviation (x̄ ± s) and compared using independent sample t-tests. Categorical data were expressed as frequencies (percentages) and compared using the χ² test, with the continuity correction χ² test employed when expected values were < 5. All tests were two-sided, and a p value less than 0.05 was considered statistically significant.

Results

Based on the inclusion and exclusion criteria, 92 patients who met the study design were finally included in this study, 56 in the HBO group and 36 in the control group. The differences in age, gender, PSH etiology, Glasgow Coma Scale (GCS) score, time to onset of PSH, CFS+DLT score and frequency of PSH episodes between the two groups were not statistically significant and were comparable (Table 2).

The time between onset and initiation of HBO therapy varied among the 56 patients who underwent HBO therapy (3-11 day), and the duration of HBO therapy ranged from 3 to 5 sessions. Compared with before HBO treatment, after 3 courses of HBO treatment, the PSH symptoms of all patients were significantly relieved ( Hyperthermia ( 36 ( 64.29 ) VS 8 ( 14.29 ), P = 0.001 ), Tachycardia ( 55 ( 98.21 ) VS 14 ( 25.00 ), P = 0.020 ), Tachypnea ( 43 ( 76.79 ) VS 8 ( 14.29 ), P = 0.001 ), Hypertension ( 48 ( 85.71 ) VS 5 ( 8.93 ), P < 0.001 ), Sweating ( 48 ( 85.71 ) VS 6 ( 10.71 ), P = 0.010 ), Posture ( 42 ( 75.00 ) VS 11 ( 19.64 ), P = 0.001 ) ) ; GSC score improved ( 5.95 ± 2.18 VS 12.31 ± 5.34, P < 0.001 ), PSH-AM (CFS+DLT) score decreased significantly ( 22.12 ± 3.12 VS 16.90 ± 4.81, P < 0.001 )（Table 3）. At 30 days of hospitalization, PSH symptoms were significantly improved in the HBO group compared to the control group ( Hyperthermia ( 8 ( 14.29 ) VS 7 ( 19.44 ), P = 0.058 ), Tachycardia ( 11 ( 19.64 ) VS 9 ( 25.00 ), P = 0.0048 ), Tachypnea ( 6 ( 10.71 ) VS 10 ( 27.78 ), P = 0.035 ), Hypertension ( 4 ( 7.14 ) VS 8 ( 22.22 ), P < 0.036 ), Sweating ( 5 ( 8.93 ) VS 9 ( 25.00 ), P = 0.036 ), Posture ( 11 ( 19.64 ) VS 14 ( 38.89 ), P = 0.043 ) ) ; GSC score was higher ( 14.12 ± 4.12 VS 12.31 ± 4.14, P = 0.002 ), PSH-AM (CFS+DLT) score was lower ( 16.9 ± 3.81 VS 19.98 ± 4.89, P = 0.010 ), intensive care unit ( ICU ) hospitalization time was shortened (18.01±5.67 VS 24.93±8.33,P=0.001)（Table 4）. It is suggested that the HBO group had significant PSH symptom relief and more awake patients.

Discussion

PSH is a complication that is not easily recognized in clinical practice. It is characterized by abnormal sympathetic excitation after severe brain injury. In recent years, HBO therapy has been used as an emerging therapy to treat many diseases [14-19]. However, there are few domestic and international reports on HBO therapy for PSH. In this study, we conducted a multicenter retrospective study to summarize and share the clinical characteristics of PSH patients undergoing ultra-early HBO therapy, and to explore the effectiveness and feasibility of this treatment method. The results of the study showed that the PSH symptom section was significantly relieved, the probability of awakening was significantly increased, and the duration of ICU hospitalization was significantly shortened after HBO treatment compared with that of patients without HBO treatment, which in turn reduced the patients’ medical expenses.

The main pathophysiological feature of PSH is sympathetic overexcitation after craniocerebral injury. Regarding the possible mechanisms of using HBO therapy to alleviate PSH symptoms. We hypothesize that there are the following aspects: （1) HBO therapy can treat the primary pathology and promote early and rapid repair of the primary pathology[22]. After the occurrence of brain injury, HBO significantly increases the oxygen supply to systemic tissues by increasing blood oxygen content and physical dissolution , and improves the oxygen diffusion rate and effective diffusion distance. Therefore, it has improved all kinds of craniocerebral injuries [23]. The GCS scores of PSH patients in this study improved significantly after 3 courses of HBO treatment. (2) The pathogenesis of PSH is currently thought to be modeled by the excitation-inhibition ratio[24]. This theory suggests that excitation originates first from the disconnection of the downstream inhibitory pathway, followed by the restoration of the inhibitory pathway to stop the seizure. After HBO treatment, the ischemia and hypoxia of the midbrain and thalamus are improved, and the inhibitory effect on the central cortex is enhanced after the function is restored, which in turn effectively relieves the clinical symptoms of PSH, such as relieving the increased respiration and heart rate, so that the frequency of PSH is significantly reduced. (3) hypertension, tachycardia, and tachypnea, during the occurrence of PSH can adversely affect the heart and respiratory system. At the same time, the combined application of multiple drugs will bring different degrees of toxic side effects on the liver, kidney, and respiratory system. We hypothesize that HBO treatment also has an ameliorative effect on the damage of multiple organs throughout the body. Therefore, it reduces and improves various complications brought by PSH.

With time, patients’ cranial self-repair and symptomatic treatment of PSH, even patients without HBO treatment will have some improvement in their symptoms. In order to clarify the exact effect of HBO in PSH symptom improvement, we chose patients with PSH when HBO treatment was not carried out as a control group. The results showed that the HBO group had more obvious PSH symptom relief, lower CFS+DLT scores, more awake patients, and shorter ICU stays. It is suggested that HBO plays a positive role in PSH symptom improvement.

The limitations of this study: (1) Due to the small prevalence of PSH, the sample size is still insufficient despite the proposed expansion of the sample size using a multicenter study. Therefore, it is not possible to further categorize the etiology causing PSH, and the therapeutic effect of HBO on different etiologies may vary, which also needs to be further investigated by expanding the sample size. (2) This study is a retrospective study, and a prospective study design is also needed to further clarify the therapeutic effect of HBO.

In summary, although PSH is rare and easy to miss diagnosis in clinic, often suggesting poor prognosis of the condition. The application of HBO treatment along with the treatment of the primary disease can alleviate the clinical symptoms of PSH and achieve certain therapeutic effects, which provides a new idea for the alleviation of PSH symptoms.

Table 1. Diagnosis of paroxysmal sympathetic hyperactivity

Table 2. Baseline data were compared between the HBO group and the control group

Table 3. Comparison of symptom improvement and GCS score before and after HBO treatment in 56 patients with PSH

Table 4. Comparison of PSH symptom improvement and clinical outcome improvement between HBO group and control group

List of Abbreviations

PSH – Paroxysmal sympathetic hyperactivity
HBO – Hyperbaric oxygen
PSH-AM – PSH assessment measure
CFS – Clinical feature scale
DLT – Diagnosis likelihood tool
GCS – Glasgow Coma Scale
ICU – Intensive care unit

DECLARATIONS

Ethics approval and consent to participate

This study was conducted with approval from the Ethics Committee of Zhengzhou People’s Hospital. This study was conducted in accordance with the declaration of Helsinki. As a retrospective study, informed consent was waived.

Availability of data and materials

The datasets used during the current study are available from the corresponding author on reasonable request.

Competing interests

The authors declare that they have no competing interests.

Funding

Henan Provincial Cardiopulmonary and Brain Resuscitation Engineering and Technology Research Center.

Authors’ contributions

HYW, SSZ, MZ designed the study, HW, YJL, SYS analyzed the data and wrote the manuscript, all investigator participated in data collection, discussion and agreed the final version of manuscript.

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