Chronic carbonmonoxide intoxication treated with or without hyperbaric oxygen treatment.

Erik Jansen, Denmark, 23 March 2000



Hyperbaric treatment of acute CO-intoxication is widely accepted as the only active treatment. However only little is known about chronic exposure to low concentrations of CO, the impact on cerebral function and the outcome of active intervention by HBO.

The present study is an attempt to benefit from the synergy of a recent study on postoperative cognitive dysfunction which has been performed within the EU under the name ISPOCD. The study has provided a basic psychometric test set, which have been validated in at least 7 countries and 5 languages. The study found postoperative cognitive dysfunction increasing by increasing age and by increased surgical intervention.


It is assumed, that the impact of a chronic CO-intoxication may be of at least same inpact on the cognitive function as major surgery. This may qualify the ISPOCD test battery to be suitable to measure within the range of interest. By stating a baseline value at first contact with the health system it may be possible sequently to follow the development of cognitive ability. It is then of interest to test for a differences in the developement of cognitive ability in an interventional group and in a noninterventional group.

The scatter of test results in normals is wide, therefore it is not possible to evaluate the potential individual damage. Only a possible effect of intervention may be detected. If an effect of intervention is found it may give rise to the assumption, that chronic intoxication is affecting the cognitive ability.


In some countries increasing public focus is cast on faulty working heating appliances, especially heaters and stoves supplied by natural gas.

In Great Britian 2 patient associations are formed as support group for alleged victims of chronic intoxication. These associations are working for compensations for their members and drawing considerable public attension to their problem. The alleged intoxicated are claiming a long lasting intellectual reduction and a chronic state of exhaustion. The symptoms are difficult to distinguish from chronic fatigue syndrome and fibromyalgia, syndromes presenting difficult diagnostics and may be connected to considerable social costs and claims for compensations.

In litterature is found little concerning chronic carbonmonoxide intoxication.

The prevalence of the condition is not known. By the increasing publicity of the state it is probable, that the recognized prevalence is increasing.

Relevance to the B-14 project.

The intoxications may be serious, the treatment is uncertain and the prevalence at present indicates, that a multitude of countries are needed in order to provide a sufficient number of patients for an evidence based conclusion.

Definition of chronic CO-intoxication (CCOI):

  1. the source of CO has to be located.
  2. a minimal concentration of xxx ppm should be found in the immediately vicinity of the source, - indicating the highest possible intoxication level.
  3. the patient should describe one or more of the following symptoms:


Inclusion: all patiens fulfilling the criteria of chronic CO-intoxication of an age 18 years and older.

Exclusion: patients with acute CO-intoxication meeting the demands:

Excluded are also patiens, who have recieved hyperbaric treatments in the time after the exposure and before evaluation to the present study.


  1. blood samples are taken to determine carboxyhemoglobin.
  2. blood samples for sign of CNS affection are taken (enolases)
  3. all patients are examined by a psychometric test battery, as set op by ISPOC.
  4. the patient are the randomized to

A patient can participate in the study only once. Only patients who have given informed consent are enrolled in the study. Patients on minor tranquillisers and hypnotics are accepted.

Exclusion criteria: Please refer to General Method Description

Psychometric tests: Please refer to General Method Description

Psychometric test battery: Please refer to General Method Description

Entry of study evaluation: The preoperative (neuro)cognitive measurement consists of a test-session and a session with questionnaires. The psychometric test battery lasts approximately 35-45 minutes.

The psychometric evaluation

The postoperative psychometric evaluation consists of two parts: a screening for confusion and the full psychometric test battery. The screening for confusion is performed with the orientation and information part of the MMSE on the morning of the first to the third postoperative day. The full psychometric test battery and the Zung Depression Rating Scale is applied to the patient on the following occasions:

The patients are then tested by psychometric tests at entry of study and 1 week, 1 month, 3 month 6 month and 1 year after the accident.

It is important to encourage high compliance with the testing in all patients.

Reference population is provided by the ISPOCD study group within year 2000

"A new reference population will be necessary to enable comparison of the study population with a control normative population. The existing normative data for the ISPOCD battery is restricted to the elderly age group (>60 years). A parallel group of similar size aged 40 - 60 years is required to enable definition of any decrement in cognitive function in the study population. Because of the greater access to a suitable spouse of relative, the control population should be more accessible in this younger age group.

It is suggested that the patient's spouse, partner , close relative or friend be invited to participate in the study as a control. A total of 200 controls must be enrolled.

This data from all younger patients will in addition provide further validation of the ISPOCD battery which will be useful for research of higher risk eg cardiac operations."

Data collection and processing


This will be similar to the ISPOCD 1 data collection with the omission of the physiological data but with the use of new data acquisition software.

All perioperative and psychometric data (Psychometric tests) will be entered into the computer using prepared menus. This can be done either directly (in the presence of the patient) or after having been recorded on paper. This menu-driven data collection facilitates the consistency and completeness of the data.

Many detailed checks on the data have been built into the software to avoid inaccurate or missing data. All data entered will be scanned for artefacts and inconsistent data before transfer electronically to the Data Management Centre.

An operation within the study period.

If a patient enrolled in the study needs an operation before termination of the study this should be recorded in the data base as an event/complication. All circumstances relevant should be noted.

All protocol deviations are to be documented and all circumstances noted.

If a patient is withdrawn from the study, the date, time and reason for drop-out is stated in the data base. In addition, a brief report which describes patient number, status of the patient at withdrawal and reason for termination is provided by the investigator and send to the coordinator.


See ISPOC General Method Description


The CCOI-state is possibly a serious state, which is threatning the wellfare of the individual. Therefore it is acceptable to adress a investigation to the patientes.

The risk of the study is to turn may be healthy individualt into the patients role, however this risk is reduced or abolished by giving the patiens information about the development of their status.

The risk of giving the intervention group HBO-treatment is considered low, as the risk of oxygen-induced seizures is assumed to be 0.1% or less and the risk of other complications as barotrauma of the ear is 0.4% ( Meyers & Thom 1995).

The applied psychometric tests are proven usefull in a study on postanaesthetic psychologic dysfunction. The test are validated in 7 countreis and languages.

Information on the spontaneous course and the effect of intervention by HBO treatment has not prevously been documented.

CCOI is of public interest and may rise series of compensation cases, which can not be closed properly due to lack of scientific background.

All participating investigators will submit this common protocol to their respective Ethics Committees overseeing human experimentation. International, regional and local requirements for informed consent and other details of human experimentation protocols are met individually by the participants

Description of the task of each participant

The clinical investigators in each centre are responsible for the organisation of the data collection efforts in their respective hospitals. They also apply for the funds to support the personnel required for the interviews and psychological testing as well as the data collection.

Time schedule

Exploitation and dissemination of results

As previously agreed and in accordance with COST B-14 group protocols.
Acknowlegment to the ISPOCD group should be stated.


The psychometric investigators need to be trained in the method. These investigators may need to meet a few times before and during the study.

Each testing is assumed to last 1 hour.

The investigators may need to travel to the patients or vice versa.

The statistic analysis is assumed to be performed by professionals.

A detailed budget is to be set up.

The expenses are proposed to be covered by public funds, insurance institutions and the gas/heating industry. A technical EU-program on gas safety is current, and may be supportive in providing funds.

To follow:

Excerpts from the ISPOCD General Method Description. (Eds.: Project leaders: Tim Johnson, Hope Hospital, Salford, UK & Jakob Trier Møller, Copenhagen University Hospital, Denmark)


Study protocol NOT finalised !!!
Send comments or expressions of interest to: Erik Jansen