Variability in Treatment for Carbon Monoxide Poisoning in Japan: A Multicenter Retrospective Survey.

BACKGROUND: The aim of this study was to identify practice differences in the treatment of carbon monoxide (CO) poisoning with or without hyperbaric oxygen (HBO2) therapy in Japan.
MATERIALS AND METHODS: Using an online survey website (Google form), we created a questionnaire and invited interested institutions to join the COP-J Study, a prospective observational study of CO poisoning in Japan.
RESULTS: Forty-eight (63%) of 76 institutions replied to the questionnaire. Thirty-three institutions (69%) administered HBO2 therapy to patients with CO poisoning, and 15 institutions (31%) did not. Consciousness disturbance on arrival, exposure to CO for a long time, and elevation of arterial carboxyhemoglobin (CO-Hb) were the major indications for HBO2 therapy. The maximum therapeutic pressures were 2.0, 2.5, and 2.8 atmospheres absolute (ATA) at 19 (58%), 6 (18%), and 8 (24%) institutions, respectively. The number of HBO2 sessions on the first day was 1-3, and 1-7 sessions were administered on days 2-7. Seventeen (35%) institutions treated patients with delayed neurological sequelae (DNS) and 15 of them used HBO2 therapy for DNS.
CONCLUSIONS: This survey indicates that HBO2 therapy for CO poisoning was varied in both the indications and practice regimens used in Japan.

1. Introduction

Based on the results of a randomized controlled trial (RCT) reported by Weaver et al. [1], hyperbaric oxygen (HBO2) therapy is thought to be essential to prevent delayed neurological sequelae (DNS) in patients with carbon monoxide (CO) poisoning. In the United States and Europe, the clinical use of HBO2 therapy for CO poisoning is reported to vary, despite several guidelines published by scientific institutions, such as the Undersea and Hyperbaric Medical Society (UHMS) and the European Committee for Hyperbaric Medicine (ECHM) [2, 3]. It is unclear how HBO2 therapy is used for CO poisoning in Japan.

We recently began a prospective observational study of CO poisoning in Japan, the “COP-J Study,” to clarify the effects of HBO2 therapy in the acute phase of CO poisoning. The COP-J Study was approved by the Japanese Society of Intensive Care Medicine (JSICM) (no. 0011). Members of the JSICM, the Japanese Society for Clinical Toxicology, the Japanese Society of Hyperbaric and Undersea Medicine, and/or the Japanese Association for Acute Medicine were invited to participate. We called for their participation at the 31st Japanese Association for Acute Medicine Chugoku-Shikoku district meeting, the 6th Japanese Undersea and Hyperbaric Medical Society Chugoku-Shikoku district meeting, the 50th annual meeting of Japanese Undersea and Hyperbaric Medical Society, and the 37th annual meeting of Japanese Society for Clinical Toxicology. A letter of invitation to the COP-J Study was sent to all 288 certified training institutions of the JSICM and to all councilors of the Japanese Undersea and Hyperbaric Medical Society Chugoku-Shikoku district meeting. This survey was performed before the COP-J Study was commenced, to identify practice differences in the treatment of CO poisoning with HBO2 therapy in Japan.

2. Methods

This study was conducted between March 2016 and July 2016. We created a questionnaire with an online survey website (Google form). An e-mail containing a link directing the responders to the survey website was sent to a responsible person at the institutions that agreed to participate in the COP-J Study. The questionnaire consisted of the following questions: data recorded in the most recent year were collated.

What type of HBO2 chamber do you have?

How many patients do you treat for CO poisoning a year?

Do you use HBO2 therapy for CO poisoning?

Which criteria do you consider to be indications for HBO2 therapy in patients with CO poisoning?

How much pressure do you use in HBO2 therapy for CO poisoning?

How many rounds of HBO2 therapy do you administer to CO poisoning patients in the 24 h after admission?

How many rounds of HBO2 therapy do you administer to CO poisoning patients between day 2 and day 7 after admission?

How long do you administer oxygen to CO poisoning patients?

How long does a patient with CO poisoning remain in bed?

Is magnetic resonance imaging (MRI) of the brain performed in the acute phase?

If yes, is the treatment altered based on the MRI findings?

If yes, what parts of the treatment are altered based on the MRI findings?

Do you treat patients with delayed neurological sequelae (DNS)?

If yes, do you use HBO2 therapy for DNS?

The results were assessed with basic descriptive analyses. We calculated the percentages of the responses to each question, using the number of centers that responded to that particular question as the denominator. Percentages were rounded to the nearest integer value.

3. Results

A total of 76 institutions received the invitation to participate in this survey and 48 (63%) institutions responded. Of these 48 institutions, 28 (58%) were university hospitals, 13 (27%) were general hospitals with emergency and critical care centers, and 7 (16%) were general hospitals without emergency or critical care centers. Twenty-one (44%) and 10 (21%) institutions had monoplace and multiplace HBO2 chambers, respectively (Table 1). Seventeen (35%) institutions had no HBO2 chamber (Table 1). The numbers of patients with CO poisoning per year were 0–1 patient at 12 institutions (12%), 2–5 patients at 18 institutions (37%), 6–9 patients at 10 institutions (21%), and >10 patients at 8 institutions (17%; Table 2).

Table 1

Type of HBO2 chamber.

	Number	%
Monoplace	21	44
Multiplace	10	21
None	17	35

Table 2

Number of patients with CO poisoning per year.

Number of patients	Number	%
0 –1	12	25
2–5	18	37
6–9	10	21
> 10	8	17

Thirty-three institutions (69%), including two institutions without an HBO2 chamber, administered HBO2 therapy to patients with CO poisoning, whereas 15 institutions (31%) did not. The two institutions that did not have an HBO2 chamber administered HBO2 therapy by transferring the patients to another hospital that had an HBO2 chamber. The indications for HBO2 therapy in CO poisoning patients at the 33 institutions are shown in Table 3. Consciousness disturbance upon arrival, exposure to CO for a long time (>12 hours), and elevation of arterial carboxyhemoglobin (CO-Hb) were the major indications for HBO2 therapy. Others included myocardial injury, age >60 years, organ failure, and nonmechanical ventilation.

Table 3

Indications for HBO2 therapy in patients with CO poisoning at 33 institutions.

	Number	%
Consciousness disturbance on arrival	19	58
Exposure to CO for > 12 hours	17	52
CO-Hb ≥ 10%	11	33
CO-Hb ≥ 20%	9	27
All cases	8	24
Other	5	15

Multiple answers allowed.

The maximum therapeutic pressure used for HBO2 therapy and the number of HBO2 sessions during the first 24 h and on days 2–7 varied across institutions (Table 4). The maximum therapeutic pressures were 2.0, 2.5, and 2.8 atmospheres absolute (ATA) in 19 (58%), 6 (18%), and 8 (24%) institutions, respectively (Table 4(a)). The number of HBO2 sessions was 1–3 during the first 24 h (Table 4(b)) and 0–7 during the following 6 days (Table 4(c)). No institution continued HBO2 therapy after the first week.

Table 5 lists the durations of oxygen administration and the period of bed rest for CO poisoning patients. The majority of institutions (28 of 48, 58%) administered oxygen to CO poisoning patients until their CO-Hb levels had normalized. Several institutions used other criteria to select the period of oxygen administration, including for 24 h after CO exposure, for >24 h after CO exposure, until the next morning, and until the recovery of consciousness. All institutions had some criterion or criteria for the duration of oxygen administration. However, 22 (46%) institutions had no criterion for the duration of bed rest.

Table 5

Duration of oxygen administration and period of bed rest for CO poisoning patients.

	Duration of oxygen administration		Duration of bed rest
	Number	%	Number	%
Until CO-Hb level normalized	28	58	7	15
For 24 h after CO exposure	5	10	1	2
For > 24 h after CO exposure	6	13	2	4
Until next morning	5	10	2	4
Until consciousness is regained	2	4	14	29
None set	0	0	22	46
Other	2	4	0	0

An MRI scan of the brain was performed in all CO poisoning patients at 14 (29%) institutions and was performed according to the severity of poisoning at 30 (66%) institutions. Brain MRI was not performed at four (8%) institutions. Of the 44 institutions that performed brain MRI for CO poisoning patients, 13 (30%) institutions altered the treatment if the findings were abnormal. The changes to treatment were increased length of follow-up (five institutions), addition of HBO2 therapy (three institutions), and administration of edaravone (two institutions).

Seventeen (35%) institutions treated patients with DNS and 15 of these performed HBO2 therapy for DNS.

4. Discussion

This survey demonstrates that, in Japan, the treatment of patients with acute CO poisoning varies, including the inclusion of HBO2 therapy. HBO2 therapy was performed for CO poisoning in 69% of the institutions surveyed, and the HBO2 therapy profiles used to treat patients with CO poisoning varied widely. These results suggest that there is no consensus regarding the treatment for acute CO poisoning, including the administration of HBO2 therapy, in Japan.

In this survey, the majority of centers (69%) gave HBO2therapy to patients with acute CO poisoning. Although it was reported that HBO2 therapy improved the neurological outcomes of patients with acute CO poisoning [1], there is no clinical consensus regarding HBO2 therapy for acute CO poisoning. The American College of Emergency Physicians Clinical Policies recommends that “emergency physicians should use HBO2 therapy or high-flow normobaric therapy for acute CO-poisoned patients” as a level B recommendation [4]. However, Hampson et al. wrote a rebuttal on HBO2therapy for acute CO poisoning [5]. They recommended that “HBO2 should at least be considered for all patients with acute, symptomatic CO poisoning.” In Japan, the same situation is present and there is no consensus on when to include HBO2 therapy for CO poisoning patients. The most recent Japanese survey revealed that only 42% of emergency and critical care centers, which usually treat patients suffering acute poisoning (including CO poisoning), had an HBO2 chamber [6]. This limited availability of HBO2 chambers might explain the low rate of HBO2 therapy for CO poisoning in Japan.

In this survey, the major indications for HBO2 therapy were consciousness disturbance upon arrival, exposure to CO for a long time, and elevated arterial CO-Hb, whereas at 24% of institutions, HBO2 therapy was administered to all patients diagnosed with CO poisoning. Compared with a European survey [3], very few institutions included criteria such as myocardial injury or pregnancy. These results might suggest that few Japanese institutions follow the ECHM consensus [7] or the UHMS committee report [8], reflecting the lack of consensus on HBO2 therapy for CO poisoning in Japan.

The present survey revealed many variations in the HBO2 therapy profiles for CO poisoning. The maximum therapeutic pressure and number of HBO2 sessions in the first 24 h or the first week were not consistent among the 33 (69%) institutions that performed HBO2 therapy for CO poisoning. These results are similar to reports from Europe and USA [3, 4]. The majority (58%) of the institutions performed HBO2 therapy at 2.0 ATA, although studies have demonstrated that HBO2 therapy at 2.0 ATA is not an effective treatment for CO poisoning [9, 10]. No Japanese institutions treat patients with HBO2 at 3.0 ATA. However, HBO2 at 3.0 ATA was used in a positiveRCT reported by Weaver et al. [1] and HBO2 at 2.5–3.0 ATA was recommended for patients with acute CO poisoning and neurological symptoms [11]. This finding may be related to the fact that 2/3 of the 31 institutions that had an HBO2 chamber had only a monoplace chamber and that, until 2012, monoplace chambers were restricted to therapeutic pressures ≤2.0 ATA by the Japanese Society of Hyperbaric and Undersea Medicine, if they were pressurized with oxygen. It seems likely that many institutions have continued using the same therapeutic pressure since 2012.

The number of HBO2 sessions performed within the first 24 h was 1–3, and the majority of institutions performed 1–7 sessions in the following 6 days. These results might be related to the health care fee for HBO2 therapy in Japan, although no effective regimen for HBO2 therapy for CO poisoning has achieved consensus in either Europe or the USA [2, 3]. In Japan, institutions can claim higher fees for HBO2 therapy only once per day within the first 7 days from the onset of CO poisoning than they can claim thereafter. Therefore, 1/3 of institutions might limit the number of HBO2 sessions to one on the first day and many institutions might continue HBO2 therapy until day 7. These results suggest that it might be important to standardize the HBO2 protocol for CO poisoning in Japan.

The majority (58%) of institutions continued oxygen administration until the CO-Hb level normalized, while almost half (46%) of the institutions did not specify the duration of bed rest. These results reflect the absence of a consensus on the duration of oxygen administration and the period of bed rest for patients with CO poisoning in Japan. Further studies are needed to establish consensus on these issues.

The survey revealed that brain MRI was performed in all CO poisoning patients at 14 (29%) institutions, and 30 (63%) institutions used brain MRI depending on the severity of poisoning. MRI is a very important examination for CO poisoning patients. It is reported that both diffusion-weighted imaging (DWI) and diffusion tensor imaging (DTI) in the acute phase are useful for predicting the onset and outcome of DNS after acute CO poisoning [12-15]. In addition, Japanese institutions have easy access to MRI because there are 51.7 MRI units per million population in Japan, which is the highest rate in the world [16].

Only 17 (35%) institutions treated patients with DNS in this survey. This suggests that it is difficult for emergency departments to follow up acute CO poisoning patients for long periods because there is a considerable interval before the onset of DNS. Of these 17 institutions, 15 performed HBO2 therapy for DNS. HBO2 therapy is reported to be useful in treating DNS [17], and it was recently reported that the combined application of HBO2 therapy and dexamethasone or N-butylphthalide improves the neurological outcome of DNS [18, 19]. However, there has been no multicenter randomized control trial of HBO2 therapy for DNS. Further research is required to clarify the effects of HBO2 therapy on DNS.

A limitation of this survey was that the survey was only conducted in those institutions that responded to the invitation to join the COP-J Study. These institutions might not be representative of institutions that treat patients with CO poisoning in Japan.

5. Conclusion

Our results show that, in Japan, HBO2 therapy for CO poisoning patients varies in not only the indications for treatment but also the practice regimens used. These results are similar to the trends reported in Europe and USA. It might be necessary to standardize the protocol for treating CO poisoning, including the indication and regimen of HBO2 therapy, in Japan.

(a) Maximum therapeutic pressure for HBO2 therapy at 33 institutions

	Number	%
2.0 ATA	19	58
2.5 ATA	6	18
2.8 ATA	8	24

(b) Number of HBO2 therapy sessions during 24 h after admission at 33 institutions

	Number	%
1	12	36
2	11	33
3	8	24
Other	2	6

(c) Number of HBO2 therapy sessions from day 2 to day 7 after admission at 33 institutions

	Number	%
None	6	18
1–3	13	39
4–7	11	33
Other	3	9