Effect of hyperbaric oxygen treatment on patients with heatstroke complicated by multiple organ dysfunction:A retrospective study

Abstract

Background

The benefits of hyperbaric oxygen (HBO) in treating animals with heat stroke (HS) have been established. This study aims to retrospectively analyze the effect of HBO on multiple organ dysfunction following HS in humans.

Methods

Retrospective data were collected from patients with HS admitted to our hospital in the past 7 years. Patients were categorized into groups based on whether they received HBO therapy. The study compared various factors, including sequential organ failure assessment (SOFA) and acute physiology and chronic health evaluation-Ⅱ (APACHE-Ⅱ) scores, mortality rates, neurological function scores, serum myocardial enzyme levels, liver, kidney, and coagulation function indicators, blood routine results, electrolyte levels, and modified Barthel index (MBI) score for standard daily living ability before treatment and after 2 and 4 weeks of treatment.

Results

The mortality rates in the HBO and control group were 0% and 8.49%, respectively. Upon admission, the HBO group had higher SOFA and APACHE-Ⅱ scores and lower neurological, coagulation, and liver functions than those of the control group. HBO treatment significantly improved SOFA, APACHE-Ⅱ, and neurological scores while relieving levels of alanine aminotransferase, aspartate aminotransferase, creatinine, and myocardial enzymes. Additionally, it mitigating lymphocyte and platelet count decline caused by HS. The MBI score was significantly enhanced after treatment in the HBO group.

Conclusions

Clinical practice advocates administering HBO therapy to patients with severe illness, organ damage, and nerve impairment. Compared with conventional treatment, combined HBO therapy demonstrated superior efficacy in alleviating multiple organ dysfunction and improving daily living ability in patients with HS.

1. Introduction

Heat stroke (HS) is a severe heat-related illness characterized by an elevated core temperature (≥40 °C), central nervous system (CNS) dysfunction, and multiple organ failure, which can be life-threatening [1,2]. It is classified into classic heat stroke and exertional heat stroke. The pathophysiology of HS involves direct heat effects on the host, a coagulopathic response, and induction of systemic inflammatory response syndrome, leading to multiple organ dysfunction syndrome (MODS). HS can induce renal and liver injuries, airway spasms, disruption of homeostatic thermoregulation, and CNS dysfunction, ultimately causing MODS, which is the main factor leading to death in patients with HS [3]. Therefore, early identification and rapid intervention are crucial for survival and a favorable neurological outcome.

Cooling techniques to lower the core temperature during the critical "golden half-hour" period after HS and early supportive treatment of MODS are two crucial measures for managing HS [2,4,5]. However, evidence supporting the superiority of any one cooling technique in classic HS is lacking [5]. Furthermore, no Food and Drug Administration-approved pharmacological therapy is currently available to reduce HS-induced MODS. Although several animal studies have shown that ulinastatin, dexmetopouril, tipredone, and activated protein C can protect against HS, no prospective study has confirmed their efficacy [[[6], [7], [8]]]. Therefore, effective noninvasive therapy is needed to treat MODS after HS and prevent death.

Previous studies have shown that hyperbaric oxygen (HBO) therapy can improve neurological function, inflammatory response, and coagulation disorders [9], thereby reducing mortality in animal models of HS [[10], [11], [12]]. In a case report, authors have successfully demonstrated the use of HBO therapy in combating hypercoagulable states, rhabdomyolysis, and renal and hepatic failure to rescue patients from HS-induced death [13]. However, few clinical studies have documented HBO therapy for managing HS-induced MODS. Furthermore, HBO therapy has not been incorporated into the guidelines for managing HS. Therefore, the objective of this study was to retrospectively analyze clinical data from patients with HS, assess the impact of HBO on the management of MODS, and establish a clinical foundation for the combined treatment of HS and MODS using HBO therapy.

2. Materials and methods

2.1. Study design and participants

Electronic medical records of patients with HS who were admitted to the General Hospital of Southern Theater Command in China between May 1st, 2016, to Sep 30th, 2023, were reviewed. The study was approved by the Ethics Committee of the General Hospital of Southern Theater Command of PLA (approval no. NZLLKZ2022015) and was conducted in accordance with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. Informed consent was waived by our Institutional Review Board because of the retrospective nature of our study.

Patients, aged 15–70 years, who met the diagnostic criteria, including classic or exertional HS with a history of exposure to hot and humid weather or strenuous activity, hyperthermia (core temperature ≥40 °C), and central nervous system abnormalities (delirium, convulsions, or disorders of consciousness), accompanied by multiple organ damage were included in this study [[14], [15], [16]]. Patients were excluded if they had pre-existing neurological dysfunction caused by stroke or traumatic brain injury, mental diseases, severe hepatic and renal dysfunction, coronary atherosclerotic heart disease, coagulation disorders before HS, pregnancy or breastfeeding, incomplete medical records, or refusal to participate in the study.

Baseline and follow-up data were collected for enrolled patients, including age, core temperature immediately upon admission, mortality rate, degree of disorder of consciousness (DOC), neurological function score, indicators of hepatic, renal and coagulation functions, routine blood examinations, and cardiac indicators within 24 h of HS upon admission. Patients were categorized into the conventional treatment group (control group) and HBO combined with conventional treatment group (HBO group), based on their receipt of HBO therapy.

2.1.1. Variables

Data on variables were collected upon admission and after 2 and 4 weeks of treatment. These variables included essential demographic information, duration of hyperthermia and DOC, neurological function scores, evaluation of the severity of MODS, serum neuron-specific enolase (NSE), myocardial enzyme markers, hepatic and renal function parameters, coagulation profile, electrolyte levels, as well as prognostic score. The degree of MODS was assessed using the sequential organ failure assessment (SOFA) and acute physiology and chronic health evaluation-Ⅱ (APACHE-Ⅱ) scores. Neurological function was assessed using the Glasgow coma scale (GCS) scores and the National Institute of Health stroke scale (NHISS) scores. Routine blood, serum electrolyte, myocardial enzyme profile, liver and kidney function index, coagulation function index, and other indicators were examined using an automatic blood routine analyzer (sysmex-XN30, Sysmex Corp., Shanghai, China), automatic biochemical analyzer (Cobas c702, Roche Diagnostics Corp., Estes Park, USA) and automatic coagulation analyzer (Stago STA-R Evolution, Stago Inc., Tianjin, China) in a biochemical laboratory of the General Hospital of Southern Theater Command of PLA.

2.1.2. Prognosis

The modified Barthel Index (MBI) was used to evaluate the activities of daily living (ADL) of patients on admission and after 2 and 4 weeks of treatment.

2.1.3. Statistics

Descriptive statistics were calculated for the variables. Categorical data are presented as counts and percentages. Continuous data are presented as mean ± standard error (X ± Sx), if they satisfied the normal distribution, and as median and interquartile range (M, P25–P75), if they satisfied the non-normal distribution. Intragroup data were compared using paired-samples t-test for normal distribution and Wilcoxon matched–pairs signed-ranks test for non-normal distribution. Differences before and after treatment between the groups were compared using the t-tests for normal distribution and Wilcoxon signed-rank sum test for non-normal distribution.

All statistical analyses were performed using the IBM SPSS Statistics v19.0 (IBM SPSS Inc., Chicago, USA). A P-value of <0.05 was considered significant.

3. Results

3.1. Patient demographics

A total of 138 patients with HS were included in the study. The control group consisted of 106 (98 male and 8 female) patients, with an average age of 21 (19–25) years. The HBO group comprised 32 (28 male and 4 female) patients, with an average age of 28 (20–41.8) years. The patients in the HBO group were older, exhibited a higher body temperature upon admission, and experienced an extended duration of DOC than those in the control group; however, no significant differences in sex, time interval from onset to admission, and cooling time were observed between the two groups (Table 1). The screening process for clinical data is shown in Fig. 1.

Table 1.

General conditions of the patients with heatstroke.

	Control	HBO	Value	P
Age (year-old)	21 (19–25)	28 (20∼41.8)**	−3.026	0.002
Gender [n (%)]			χ2
Male	98 (92.5%)	28 (87.5%)	0.76	0.38
Female	8 (7.5%)	4 (12.5%)
Core temperature (°C)	39.8 (38.9–40.5)	40.8 (40–42)**	−4.56	＜0.001
Cooling time (hour)	3 (1–5)	3.98 ± 0.4	−1.56	0.12
Duration of DOC (day)	0 (0∼0.3)	3.5 (0.63–8.5)**	−5.54	＜0.001
Time from onset to admission (hour)	3.75 (2–6)	3 (2.06–4.88)	−1.05	0.29

Data are shown as mean ± S.E.M. or M(P25～P75), *P＜0.05，**P＜0.01 vs the control group. HBO: hyperbaric oxygen; DOC: disorder of consciousness.

Fig. 1.

Screening process of patients' clinical data for this study HBO: hyperbaric oxygen; TBI: traumatic brain injury; CHD: coronary atherosclerotic heart disease; CKD: chronic kidney disease.

3.1.1. Mortality, neurological function score, and assessment of MODS

The control group had a mortality rate of 8.49%, which was higher than that of the HBO group but without statistical significance (0%, P = 0.088). The period from the onset of HS to death was 22.2 ± 3.16 days. Upon admission, the HBO group had significantly higher NHISS, SOFA, and APACHE II scores and a lower GCS score than those of the control group. The SOFA and APACHE II scores of both groups significantly decreased after 2 and 4 weeks of treatment. After 2 and 4 weeks of HBO therapy, the GCS score significantly increased, whereas the NHISS score decreased significantly. After 4 weeks of treatment, the GCS scores decreased in the control group, and both groups demonstrated a decrease in NSE levels compared with those before treatment. The conventional treatment did not yield a significant improvement in the NHISS score. The difference in the change in NSE levels between the two treatment groups was nonsignificant. After 2 and 4 weeks of treatment, the efficacy of HBO therapy in enhancing the GCS, NIHSS, SOFA, and APACHE II scores surpassed that of conventional treatment (Fig. 2A–E).

Fig. 2.

Neurological scores, severity of critical illness scores and modified Barthel index scores of patients with heatstroke before and after treatment. *P < 0.05, **P < 0.01 vs. the control group. ^#P < 0.05, ^##P < 0.01 vs. pretreatment. ^▲P < 0.05, ^▲▲P < 0.01 indicated the comparison of difference before and after treatment between the HBO and control groups. A: Glasgow coma scale (GCS) scores before and after treatment in each group; B: National Institute of Health stroke scale (NHISS) scores before and after treatment in each group; C: Levels of neuron-specific enolase (NSE) before and after treatment in each group; D: Sequential organ failure assessment (SOFA) scores before and after treatment in each group; E: Acute Physiology and Chronic Health Evaluation-Ⅱ (APACHE-Ⅱ) scores before and after treatment in each group; F: Modified Barthel index (MBI) scores before and after treatment in each group.

3.2. Blood routine and serum electrolytes concentration

Upon admission, the HBO group had significantly lower serum sodium (Na⁺) concentrations, lymphocyte (LYM) and platelet (PLT) counts, and hematocrit (HCT) levels than those of the control group. The white blood cell (WBC) and neutrophil (NEU) counts did not significantly differ between the two groups. After 2 weeks of treatment, the serum potassium (K⁺) levels and LYM and PLT counts in the HBO group were significantly higher than those before treatment. Furthermore, in the control group, PLT counts were significantly higher and Na⁺ levels, HCT, WBC and NEU counts were significantly lower than those before treatment. After 4 weeks of treatment, LYM and PLT counts in HBO group were significantly higher and WBC and NEU counts were significantly lower than those before treatment. Furthermore, in the control group, K⁺ levels and PLT counts were significantly higher and Na⁺ levels, WBC and NEU counts were significantly lower than those before treatment. The impact of HBO therapy on the elevation of PLT and LYM counts was more pronounced after 2 and 4 weeks of treatment than that of conventional treatment (Table 2).

Table 2.

The blood routine, serum electrolyte concentration, and coagulation function index in each group of patients with heatstroke.

Score	Group	pre-treatment	2 weeks pro-treatment			4 weeks pro-treatment
		$\bar{\chi }$±Sx (M,P25∼75)	$\bar{\chi }$± Sx (M,P25∼75)	z/t	P	$\bar{\chi }$± Sx (M,P25∼75)	z/t	P
Serum electrolytes concentration
K+ (mmol/L)	Control	3.86 ± 0.05	4, 3.7–4.2	−1.96	0.05	4, 3.9–4.3 ##	−0.14	0.89
	HBO	3.53 ± 0.11	3.9, 3.7–4.1 ##			3.7, 3.6–4 **
Na+ (mmol/L)	Control	142, 140∼143.3	139.1 ± 0.3 ##	−1.74	0.083	140, 138–141##	−1.66	0.09
	HBO	139.3 ± 0.74 *	139.5, 136∼141			140, 135∼141
Blood routine
WBC (109/L)	Control	9.5, 6.7–13.5	7.12, 6.26–9.88 ##	−0.20	0.85	6.92, 5.95–8.44 ##	−1.25	0.21
	HBO	9.2, 6.6–12.34	7, 6.08–8.77			6.88, 5.3–8.86 #
NEU (109/L)	Control	7.02, 4.18–10.3	4.73, 3.59–7.54 ##	0.03	0.98	4.1, 3.4–5.21 ##	−0.98	0.33
	HBO	7.32 ± 0.60	5.03, 3.84–7.4			4.56, 3.26–6.64 ##
LYM (109/L)	Control	1.64, 0.9–2.24	1.27, 1.02–1.92	−2.92	0.004	1.82 ± 0.07	−2.26	0.02
	HBO	0.62, 0.32–1.08 **	1.25 ± 0.09##			1.49 ± 0.11 *##
PLT (109/L)	Control	146.3 ± 12.5	158.2 ± 29 ##	−4.06	0.000	214.2 ± 21.3 ##	−2.64	0.008
	HBO	93.5,50∼140.3 **	252, 172–404 **##			228,196.5–272.5##
HCT	Control	0.42,0.38–0.44	0.32 ± 0.02##	−0.16	0.87	0.35 ± 0.02	−0.16	0.87
	HBO	0.37 ± 0.01**	0.33 ± 0.01 **			0.36 ± 0.01**
Coagulation function
FDP (μg/mL)	Control	4.1, 3.53–11.4	2.5, 0.8–4.79 ##	−2.0	0.046	1.05, 0.54–2.36 ##	−0.62	0.53
	HBO	21.6, 7.7–64.6 **	6.8, 4.3–11 **##			4.95, 2.8–10.4**##
PT (sec)	Control	15.9, 14.7–19.85	13.8, 12.8–16.5 ##	−3.36	0.001	13, 12.7–13.8 ##	−1.80	0.07
	HBO	18.1, 15.9–23.7*	13.3, 12.6–14 ##			13, 12.75–14.25 ##
APTT (sec)	Control	40.3, 36.7–47.4	38.9, 36.2–43.3	−2.8	0.005	38.1, 35.6–41.4 ##	−2.03	0.043
	HBO	44.2, 38.6–67.5	37.73 ± 1.2 ##			39.2 ± 1.41##
D-D (μg/mL)	Control	3.49, 0.53–19.97	4, 3.12–12.3 #	−3.67	＜0.001	4, 3.63–6.43 #	−3.97	＜0.001
	HBO	9.75, 4.3–19.9 **	2.42, 1.73–4 **##			1.97, 0.8–3.35**##
INR	Control	1.43, 1.2–2.3	1.05, 0.97–1.36 ##	−2.27	0.023	0.99, 0.96–1.09 ##	−1.25	0.21
	HBO	1.46, 1.19–2	1.02, 0.96–1.1##			0.99, 0.96–1.07 ##
vWF:Ag (%)	Control	316.3 ± 19.38	231, 180.8–347.5 #	−0.32	0.75	232,165.8–292 ##	−0.93	0.36
	HBO	391, 357∼420	341, 185∼383.5 #			255.5 ± 21.2 ##

*P < 0.05, **P < 0.01 vs the control group. ^#P < 0.05, ^##P < 0.01 vs before the treatment. z/t value indicated the comparison of difference before and after treatment between the HBO and control group. Data are shown as Mean ± Standard error ($\bar{\chi }$ ±Sx) if they satisfied the normal distribution or median and as quartile in an interquartile range (M, P25～P75) if they satisfied the non-normal distribution. SOFA: sequential organ failure assessment; APACHE-Ⅱ: Acute Physiology and Chronic Health Evaluation-Ⅱ; GCS: Glasgow coma scale; NHISS: National Institute of Health stroke scale; NSE: serum neuron-specific enolase; WBC: white blood count; PLT: blood platelet count; HCT: red blood cell specific volume; NEU: neutrophil count; LYM: lymphocyte count. K⁺: potassium concentration, Na⁺: sodium concentration; PT: prothrombin time; APTT: activated partial thromboplasting time; FDP: Fibrinogen degradation products; vWF:Ag: Von willebrand factor antigen; D-D: D-dimer. INR: international normalized ratio.

3.3. Parameters of coagulation function

Upon admission, fibrinogen degradation products (FDP) and D-dimer levels and prothrombin times (PTs) were significantly higher in the HBO group than in the control group. After 2 and 4 weeks of treatment, FDP, D-dimer, and Von Willebrand factor antigen (vWF:Ag) levels and the international normalized ratios (INRs) and PTs in both HBO and control groups were significantly lower than those before treatment. Notably, activated partial thromboplastin times (APTTs) decreased after a 2-week treatment only in the HBO group. After 2 weeks of treatment, the FDP and D-dimer levels and the PTs, APTTs, and INRs significantly improved in the HBO group than in the control group. After 4 weeks of therapy, the HBO group exhibited significantly greater improvements in the APTT and D-dimer levels than those of the control group (Table 2).

3.4. Indicators of myocardial injury, hepatic function, and renal function

Upon admission, lactate dehydrogenase (LDH) levels were significantly lower in the HBO group than in the control group. However, creatine kinase MB (CKMB), myoglobin, high-sensitivity cardiac troponin T (hsTnT) levels and left ventricular ejection fraction values (LVEF), as measured by ultrasonography, did not significantly differ between the two groups. After 2 and 4 weeks of treatment, CKMB, myoglobin, hsTnT, and LDH levels in the HBO group significantly decreased compared with those before treatment. The levels of CKMB, myoglobin, hsTnT and LDH in the control group also significantly decreased after 2 or 4 weeks of treatment. After 2 weeks of treatment, the ameliorative effect of HBO therapy on LDH, hsTnT, and LVEF was significantly stronger than that of the conventional therapy, and after 4 weeks of treatment, the ameliorative effect of HBO therapy on hsTnT was significantly stronger than that of the conventional therapy.

Upon admission, the HBO group had significantly higher levels of alanine aminotransferase (ALT) than those of the control group. After 2 weeks of treatment, the levels of ALT, aspartate aminotransferase (AST), creatine kinase (CK), and creatinine significantly decreased in the HBO group. In the control group, the levels of AST/ALT, total bilirubin (TB) and CK significantly decreased. The ameliorative effect of HBO therapy on ALT, AST, and creatinine levels was significantly stronger than that of the conventional therapy. After 4 weeks of treatment, HBO therapy significantly reduced ALT, AST, TB, CK, and creatinine levels compared with those before treatment. The control group exhibited a decrease in AST, AST/ALT, TB, CK, creatinine and urea nitrogen (BUN) levels. No significant difference was observed in cystatin C levels before and after conventional and HBO treatment. The ameliorative effect of HBO therapy on ALT, AST/ALT, and creatinine levels was significantly superior to that of the conventional therapy (Table 3).

Table 3.

The indices of hepatic, renal and heart function in each group of patients with heatstroke.

Index	Group	pre-treatment	2 weeks pro-treatment			4 weeks pro-treatment
		$\bar{\chi }$± Sx (M,P25∼75)	$\bar{\chi }$± Sx (M,P25∼75)	z/t	P	$\bar{\chi }$± Sx (M,P25∼75)	z/t	P
Hepatic function
ALT (U/L)	Control	77, 25.3–283	95, 51.8–181.3	−3.14	0.002	70, 38∼121.5	−2.64	0.008
	HBO	244,50.3–1193 *	87.2 ± 9.66 #			51, 33.5–104.8 ##
AST (U/L)	Control	102, 33.8–305.5	64, 32∼166.5	−2.70	0.007	36, 21–77 ##	−1.57	0.12
	HBO	150.5, 58∼534.5	50, 27–78 ##			41, 25∼87.5 ##
AST/ALT	Control	1.33, 0.7–2.1	0.8, 0.4–1.26 ##	−0.82	0.41	0.68,0.39–1.04##	−2.30	0.02
	HBO	1.04,0.36–1.86	0.65, 0.51–1.21			0.84, 0.65–1.24*
TB (μmol/L)	Control	18.5, 12.4–33.3	13.4, 10.5–22 ##	−0.58	0.56	11.6, 8.1–16.6 ##	−0.07	0.94
	HBO	21.7, 12.9–63.2	13, 9.3–26.8			11.8, 8.6–23.5 #
Renal function
CK (U/L)	Control	607, 315∼1916	228,91∼891.8 ##	−0.98	0.34	118, 64∼580.5 ##	−0.58	0.56
	HBO	696, 371.8–1389.5	114, 61–386 *##			147.5, 72.3–362.5 ##
cystatin C (mg/L)	Control	0.89, 0.78–1.32	0.98, 0.81–1.22	−0.31	0.76	0.9, 0.79–1.06	−0.89	0.372
	HBO	1.04, 0.84–1.39	1.12, 0.91–1.52			1.0, 0.9–1.22 **
creatinine (μmol/L)	Control	111,87∼176	92, 75.3–120	−2.52	0.012	83, 72–98 ##	−2.26	0.024
	HBO	131, 83.8–156.8	69, 54–100 **##			60, 48.5–77.75 **##
BUN (mmol/L)	Control	6.5, 4.7–9.1	6.2, 4.4–9.6	−1.89	0.059	4.8, 3.7–6.3 ##	−0.70	0.56
	HBO	7.1, 4.73–8.18	5.3, 3.85–12.05			5.35, 3.9–7.7
Myocardial injury levels
CKMB (μg/L)	Control	11.5, 3.36–57.67	4.6, 1.5–14.6 #	−1.12	0.26	4.2, 2.3–8.6 ##	−0.26	0.80
	HBO	12.7, 8.14–21.4	2.93,1.5–7.34 ##			3.13, 1.5–10.25 ##
Mb (μg/L)	Control	1042, 119.4–2573.8	81, 22.2–684 ##	−1.7	0.08	74, 34.4–409.8 ##	−1.13	0.26
	HBO	397, 158∼2094	140, 41∼181.7 ##			49.4, 23–272 ##
hsTnT (pg/mL)	Control	150, 39.9–729.5	12, 7.5–70.1 ##	−2.2	0.027	14.4, 8.5–51.2 ##	−1.88	0.04
	HBO	176, 74∼589.2	19.7, 13∼40.4 ##			18, 11.7–45 ##
LDH (U/L)	Control	315, 217.5–505.5	212,165–396 ##	−1.97	0.049	202, 165–280 ##	−1.74	0.082
	HBO	498.5, 319–1187 *	305.8 ± 39 ##			283.5, 209.5–327 *##
LVEF (%)	Control	60, 59∼62	60, 58∼61.3	−2.20	0.028	61, 60∼64	−0.98	0.33
	HBO	60, 57∼61.3	60, 60∼62.5			61.8 ± 0.37#

*P < 0.05, **P < 0.01 vs the control group. ^#P < 0.05, ^##P < 0.01 vs pre-treatment. z/t value indicated the comparison of difference pre- and pro-treatment between the HBO and control group. Data are shown as Mean ± Standard error ($\bar{\chi }$ ±Sx) if they satisfied the normal distribution or as quartile in an interquartile range (M, P25～P75) if they satisfied the non-normal distribution. ALT: alanine transaminase; AST: aspertate aminotransferase; TB: total bilirubin; CK: creatine kinase; BUN: urea nitrogen; CKMB: Creatine kinase MB; Mb: myoglobin; LDH: lactate dehydrogenase; hs-tnt: hypersensitive troponin T. LVEF: Left Ventricular Eject Fraction.

3.4.1. Prognosis

Upon admission, the MBI score was significantly lower in the HBO group (0, 0–15) than in the control group (50, 40–60). After 2 and 4 weeks of treatment, the MBI scores in the HBO group (2 weeks: 80, 60–100; 4 weeks: 87.5, 66.25–100) and the control group (2 weeks: 100, 80–100; 4 weeks: 100, 80–100) significantly increased compared with those before treatment. The effect of HBO therapy on improving MBI score was significantly superior to that of the conventional therapy (Fig. 2 F).

4. Discussion

In this study, the HBO group exhibited significantly higher SOFA/APACHE Ⅱ scale and neurologic function scores, levels of coagulation function indicators, ALT, and LDH upon admission than the control group. Additionally, patients in the HBO group presented with more electrolyte disturbances, suggesting that clinicians often opt for HBO therapy in patients with HS and severe medical conditions, multiple organ damage, and significant nervous system impairments. Patients with HS typically present with hyperkalemia and hyponatremia [16]. In the HBO group, lowered sodium levels were observed, which may be attributed to severe nervous system damage causing disturbances in water and electrolyte balance. HBO treatment significantly improved the SOFA and APACHE II scores, alleviated neurological, coagulation, hepatic, and renal dysfunctions, relieved myocardial damage, and improved the decline in lymphocyte and platelet counts caused by HS. The ADL were significantly lower for the patients in the HBO group than those in the control group before treatment. Nonetheless, the HBO therapy significantly enhanced the ADL of patients with HS.

The occurrence of HS can lead to systemic multiple organ dysfunction, characterized by neurological, coagulation, hepatic, and renal dysfunction, rhabdomyolysis, and myocardial and intestinal damage, as well as potential immune dysfunction. The course of HS comprises three phases, including the emergency period of hyperpyrexia-induced nerve injury, the blood system-enzymatic reaction stage (which peaks 24–48 h after onset), and the advanced stage of hepato-renal dysfunction (lasting for ≥96 h), which are particularly pronounced in exertive HS [17]. The pathophysiological mechanism primarily involves dysregulation of body temperature due to high temperatures and inadequate cardiac output to meet metabolic demands, leading to a progressive increase in core temperature and exacerbation of cytotoxic effects and inflammatory reactions, ultimately resulting in multiorgan failure. The development of MODS after HS is the consequence of a combination of direct thermal tissue damage, coagulopathy, and systemic inflammatory response syndromes triggered by endotoxin, cytokines, and other immunomodulators [18]. Therefore, the management of MODS in cases of HS necessitates a comprehensive approach targeting various physiological systems.

This study demonstrated that HBO exerts a therapeutic impact on HS-induced MODS, encompassing inflammatory, coagulation, and organ dysfunction, particularly in the neurological system. The protection of the brain is a fundamental objective in HBO treatment for HS as this can effectively mitigate potential damage to other organs [[2], [9]]. Previous findings suggested that HBO effectively regulates HS-induced oxidative damage, apoptosis, and inflammatory response in the hypothalamus, brainstem, and hippocampus, leading to the restoration of neural function abnormalities in rat models [10]. Consistent with the previous studies, in our study, the HBO treatment significantly improved the GCS and NHISS scores of patients with HS, indicating its potential in alleviating consciousness disorders and neurological dysfunctions, such as motor impairment, sensory deficits, and balance issues [10].

During the acute inflammatory phase, HBO therapy was highly effective in mitigating the decrease in lymphocyte count than the conventional treatment. The WBC and NEU counts significantly decreased following treatment in both the groups. The NEU to LYM ratio as calculated from the WBC differential count is considered a promising marker for the prognosis in patients with various diseases, including sepsis [19]. These findings indicate that HBO can alleviate immune dysfunction and acute inflammation associated with HS. Easing the inflammatory response is crucial in interrupting the detrimental cycle of "inflammation-to-high fever-to-tissue damage."

Upon admission, the HBO group exhibited a more pronounced impairment in coagulation function compared with that of the control group. The HBO therapy significantly increased the PLT count and decreased FDP, PT, APTT, D-dimer, INR, and vWF:Ag values after 2 and 4 weeks of treatment, thereby effectively improving coagulation disorder. Coagulation dysfunction is an autonomous risk aspect for HS-induced mortality and contributes to poor prognosis [20]. The 90-day survival rate of patients with PLT abnormalities during admission is lower, and the incidence of MODS is higher than heat stroke patients with normal PLT [21]. Therefore, the therapeutic effects of HBO therapy on coagulation function are of paramount importance in improving prognosis.

This study revealed that that the hepatic dysfunction of the patients persisted for up to 4 weeks after HS. Before treatment, the HBO group exhibited significantly elevated levels of ALT and APACHE II score than those of the control group. The APACHE II score plus cystatin C shows the best performance for predicting acute kidney injury [22]. After a treatment duration of 2 or 4 weeks, HBO therapy significantly ameliorated markers of liver and kidney injury. These findings highlight the potential of HBO therapy to effectively alleviate liver and kidney dysfunctions caused by HS, thereby demonstrating the substantial impact of this condition on long-term abnormal functioning of these organs. Regarding cardiac function, the indicators of myocardial damage was mitigated within 4 weeks after treatment. No significant change in cardiac ejection fraction before and after treatment was identified in the control group in this study. The improvement in the levels of CKMB, hsTnT, and LVEF at 2 weeks after HBO treatment was superior to that of the conventional treatment, suggesting that early administration of HBO therapy may expedite cardiac recovery.

The MBI score in the HBO group was notably lower than that in the control group before treatment. However, in cases where conventional treatment measures could not rescue a patient from HS-induced death, early intervention with HBO treatment displayed promising results [13]. Moreover, the MBI score in the HBO group demonstrated a significant improvement at 2 and 4 weeks after HBO treatment when compared with that of the control group. The implementation of HBO therapy is suggested to enhance the prognosis and functional capacity of patients with more severe HS complicated with MODS.

This study was limited by being a retrospective single-center study. A multicenter prospective study should be conducted to verify the efficacy of HBO therapy for HS-induced MODS.

5. Conclusions

The current clinical practice involves the administration of HBO therapy to patients presenting with severe illness, significant organ damage, and profound nerve impairment. In combination with conventional treatment, HBO has the potential to effectively alleviate multiple organ dysfunction, including neurological, hepatic, renal, coagulation dysfunction, and myocardial injury caused by HS. Additionally, HBO can enhance patient daily living abilities and improve their quality of life. Thus, HBO has the potential to become a feasible treatment option for managing HS and mitigating its enduring consequences on patients, especially in those with more severe MODS and nervous system injury.

Ethics approval and consent to participate

The experimental protocols were approved by the Use Committee at The General Hospital of Southern Theater Command of PLA (approval no. NZLLKZ2022015).

Consent for publication

All authors reviewed the manuscript and approved the publication.

Data availability statement

Data will be made available on request.

Funding

This work was supported by grants from the National Natural Science Foundation of China [No. 82072143], Natural Science Foundation of Guangdong Province of China [No. 2021A1515010170].

CRediT authorship contribution statement

Xiao-xiao Ni: Writing – original draft, Project administration, Funding acquisition, Formal analysis, Data curation. Nian-bo He: Methodology, Formal analysis, Data curation. Ye-qun Guo: Validation, Software, Formal analysis. Yi-xuan Dou: Validation, Investigation. Xiao-juan Xie: Visualization, Methodology. Zhi-feng Liu: Writing – review & editing, Investigation, Funding acquisition.

Declaration of competing interest

The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Zhi-feng Liu reports financial support was provided by National Natural Science Foundation of China. Zhi-feng Liu reports financial support was provided by Natural Science Foundation of Guangdong Province of China. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. All authors claim that we have no conflicts of interest to disclose.