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ECONOMICS, EDUCATION, AND HEALTH SYSTEMS RESEARCH

The Influence of Protocol Pain and Risk on Patients’ Willingness to Consent for Clinical Studies: A Randomized Trial

Tanja A. Treschan, MD^*, Thomas Scheck, BS^*, Alexander Kober, MD^*, Edith Fleischmann, MD^*, Beatrice Birkenberg, MD^*, Brigitte Petschnigg, RN^*, Ozan Akça, MD^,||, Franz X. Lackner, MD^*, Elisabeth Jandl-Jager, PhD, and Daniel I. Sessler, MD^,,||

*Department of Anesthesia and General Intensive Care, University Clinic for Psychoanalysis and Psychotherapy, and the Ludwig Boltzmann Institute, University of Vienna, Austria; and the Outcomes Research^® Institute and ||Department of Anesthesiology, University of Louisville, Kentucky

Address correspondence and reprint requests to D. Sessler, MD, University of Louisville, 501 East Broadway, Suite 210, Louisville, KY 40202–3866. Address e-mail to sessler{at}louisville.edu On the World Wide Web: www.or.org.

	Abstract

Top Abstract Introduction Methods Results Discussion Appendix A Appendix B Appendix C References

 
We tested the hypothesis that the risk or discomfort associated with a clinical trial influence patients’ decisions to participate. Simultaneously, we evaluated factors likely to influence patients’ decisions such as understanding of the risk and discomfort associated with the study, patient age, educational level, and psychological status. With IRB approval, participants, who believed they were being asked to participate in a real trial, were presented one of three sham protocols: no risk or pain (Control, n = 48), pain but no risk (Pain, n = 51), or risk but no pain (Risk, n = 51). Patients were debriefed at the end of the interview. Our major outcome measures were (a) understanding risk or pain associated with the proposed studies, (b) the extent to which patients felt pressured to participate, and (c) willingness to participate. Whereas understanding was similar in all groups (Control, 68%; Pain, 67%; and Risk, 72%), willingness to participate differed significantly (Control, 64%; Pain, 35%; Risk, 26%; P < 0.001). Patients who understood the level of risk or pain associated with the protocols were twice as likely to participate than those who did not (49% versus 24%; P = 0.003). Nine percent agreed to participate in the risky or painful protocols without understanding the risks involved. Patients who felt pressured did not agree to participate. Thus, the consent process protected patients, although for unexpected reasons. Understanding was poor, but patients who did not understand the risks or pain involved or who felt pressured rarely consented. Consequently, relatively few patients unknowingly agreed to participate in risky or painful studies.

IMPLICATIONS: We tested the hypothesis that the risk or discomfort associated with a clinical trial influence a patient’s decision to participate. Patients who understand the risks involved are twice as likely to consent. In contrast, those who feel pressured do not agree to participate. Many patients are willing to participate in risky or painful studies, apparently for altruistic reasons.

	Introduction

Top Abstract Introduction Methods Results Discussion Appendix A Appendix B Appendix C References

 
Some clinical studies involve considerable risk; others cause pain or discomfort to the participants. Neither is inherently unethical, even when there is no potential benefit to the participants, and neither violates the Nuremberg Code, Declaration of Helsinki, or more recent guidelines (1). However, such studies are morally indefensible unless the participants have freely provided truly informed consent and fully understand the risks and discomfort associated with the proposed protocol. However, there are few data about the influence of risk and pain or discomfort levels on patients’ decisions to participate in clinical trials. Numerous guidelines and regulations detail elements that informed consent documents must include R1-118397 (1,2). A number of studies suggest that patients might misunderstand salient aspects of consent documents, including the study objective and the concept of randomization R3-118397 R4-118397 R5-118397 R6-118397 (3–7). However, a critical element of informed consent is that potential participants fully understand the associated risks and discomfort. Surprisingly, few studies evaluate this aspect of the consent process.

There are a number of other factors likely to undermine free and rational choice during the consent process. Assuming that patients understand the risks and discomfort associated with clinical trials, individuals must be able to make a free and rational decision about participation. For example, patients who are depressed or fatalistic may feel powerless to refuse. Similarly, patients who feel pressured by investigators may agree to participate in studies that they would otherwise reject.

Therefore, we tested the hypothesis that the risk or discomfort associated with a clinical trial influence a patient’s decision to participate. Simultaneously, we evaluated factors likely to influence a patient’s decision to participate such as understanding of the risk and discomfort associated with the study, patient age, educational level, and psychological status.

	Methods

Top Abstract Introduction Methods Results Discussion Appendix A Appendix B Appendix C References

 
Our study was approved by the IRB of the University of Vienna and conducted in the General Hospital of Vienna from June 1999 through May 2000. We studied patients between 19 and 80 yr of age who were scheduled to undergo minor surgery with general anesthesia. On the afternoon before surgery, suitable patients were selected according to their availability on the ward. We excluded patients who were in pain, had a diagnosis of cancer, were unable to give informed consent, or did not speak fluent German.

Patients were asked if they would be willing to be interviewed and consider participation in a clinical trial. They were told that the purpose of the interview was to evaluate the influence of risk and discomfort associated with participation in clinical trials on patients’ willingness to participate. Patients were informed that the process would take approximately 1 hr and would involve completing a number of questionnaires and the presentation of a proposed clinical study. Patients were not told that they would be presented with sham protocols. They therefore believed that a decision to participate in the proposed clinical trial would result in perioperative study-related procedures. They were specifically informed that they could discontinue the interview at any time without any compromise to their care. Among the 154 patients we approached, 150 agreed to participate in the interview and consented in writing. We simultaneously recorded demographic characteristics and the type of surgery that was scheduled.

All interviews were conducted in German, in a private setting, and all documents were in German. A subset of 100 patients was asked to complete two short oral questionnaires. The first was the Hospital Anxiety and Depression Scale (HADS) (8), and the second was the Locus of Control Evaluation (IPC) (9). IPC refers to the subject’s attitude towards control of life aspects. It is characterized by three dimensions: (a) Internality, a measure of a person’s belief in internal power or forces to influence one’s life; (b) external Power by others, a measure of how much one feels that their own life and faith are ruled by others; and (c) external control by Chance, a measure of a person’s perception that life progression is arbitrarily controlled. Answers are quantified by stanine values. The higher a stanine value, the more weight a dimension has. For example, people with high Internality have a strong belief that life is largely in their control. These people will therefore have low external Power scores. In contrast, people with low Internality and high external Power or high Chance stanine values believe that they fail to control important aspects of life but are instead ruled by other people or chance.

Each of the 150 participating patients was then presented with one of three versions of a study protocol that involved different degrees of risk and discomfort. The version was randomly assigned by a computer-generated randomization code. The randomized assignment was maintained in sealed, opaque envelopes that were only opened just before the presentation of the proposed study. The presented versions were based on a study that was actually performed at the University of Vienna the previous year R10-118397 (10,11). The first version involved little if any risk or pain (Control), the second required additional procedures that were described as provoking considerable pain and discomfort (Pain), and the third involved additional procedures that were described as inducing risk of injury (Risk). The presented protocols each involved randomized assignment to routine perioperative oxygen (fraction of inspired oxygen = 30%) or supplemental oxygen (fraction of inspired oxygen = 80%). The additional procedures in the discomfort and risk protocols included insertion of a subcutaneous upper-arm catheter for measurement of tissue oxygen tension, insertion of an expanded polytetrafluoroethylene implant adjacent to the surgical incision for evaluation of collagen deposition, and computerized thorax tomography on the first postoperative morning.

The patients were presented with an informed consent document corresponding to their randomized group assignment. The documents included the purpose of the study, the procedures involved, and the level of discomfort or risk. Patients were informed that the study was designed to study wound healing and that the aim was to improve wound healing. They were told that they might not directly benefit from participation, but the results of the study would help improve the care of future patients.

The sections on risks and discomfort were blunt and clearly explained the potential danger or discomfort. For the Control group (Appendix A), this section specified: extra oxygen is harmless and the wound evaluations are painless. This study thus poses essentially no risk and will not produce any significant pain.

In contrast, the section on risks and discomfort for the Pain group (Appendix B) specified: extra oxygen is entirely harmless; furthermore, the proposed procedures are risk free. However, the tests that will be performed for this study are all painful. Daily inspections of surgical wounds require removing the dressing and pressing on my incision, which will be painful. The plastic tubes inserted into my arm and near my incision are harmless but can be painful for some hours. Being moved to the Radiology Department will be especially uncomfortable because I will have to remain still on a hard table. Obtaining the sample of blood from an artery in my wrist is painful. This pain can last several days.

Finally, the informed consent document for the Risk group (Appendix C) specified: the extra oxygen that will be given as part of this study is potentially dangerous and may cause collapse of my lungs. If that happens, I will need to be connected to a breathing machine and stay in the intensive care unit. This is risky because it might lead to pneumonia and dysfunction of other organs. The tubes that will be inserted in my arm and near my incision will cause bruising. They may also cause tissue damage, which could require surgery, or an infection that would require antibiotic treatment and an extra week of hospitalization. The special radiograph-scan the day after surgery will expose me to radiation. The risks of radiation exposure include cancer, vision problems, and infertility. Sampling blood from my artery may cause substantial damage to the vessel; an operation may be required to repair this vessel and prevent permanent injury to my fingers.

Patients were interviewed by one of five investigators: (a) a female anesthesia nurse, (b) a male senior medical student, (c) a recent male medical school graduate, and (d) two female anesthesia residents. All were native German speakers. Interviewers were instructed to neutrally present the study and to read out the exact wording of the consent forms and questionnaires. Personal comments to influence the decision making process were not allowed. Additional information or explanations were given if requested by the patients.

Patients were approached with the request to consent for the interview. After introduction of the project and with written informed consent, patients were then presented with HADS and IPC questionnaires and their randomly assigned version of the proposed study. The interviewing investigator explained the proposed procedures in considerable detail. The appropriate risk and discomfort paragraphs above were read out loud to each patient. The patients were given time to read the study documentation and consent forms, and questions were answered. Participants were then asked to initial the appropriate risk and discomfort paragraph to show that they had read and understood it. However, the interviewer did not remind participants to initial the relevant paragraph if they neglected to. The patients were given a few minutes to decide whether or not to participate in the proposed study. They were not permitted to call or talk with relatives or friends and were told that their surgeons were unavailable for consultation. Whether they accepted or declined participation, patients were subsequently given a separate form regarding their understanding of the risks involved in participation. They were asked to mark the statement they found most applicable:

1. A. Participation in this study is not associated with any additional risks, discomfort, or pain.
   
2. B. Participation in this study is associated with additional risks but does not cause any pain or discomfort.
   
3. C. Participation in this study is not associated with additional risks but might cause pain and discomfort.
   

Finally, patients were asked to complete a short questionnaire concerning factors that influenced their willingness to consent. This form was slightly modified from Mingus et al. (12). At that time, we told the patients that the interview was over. We thanked them for their willingness to participate in our research. It was explained that they had been presented with sham protocols and that no study-related procedures would be performed during or after surgery. It was pointed out that our actual study purpose was to evaluate the consent process per se and that we used the deceptive nature of the interview to investigate their decision making process.

The results of the HADS were classified as anxiety or depression when subscale scores exceeded 7. IPC scales were classified as low when stanine values were less than 4, average when they were between 4 and 6, and high when the values exceeded 6. Education was defined as low (up to 9 yr), medium (10–13 yr), or high (more than 13 yr). Data analysis was restricted to patients completing the entire study. Differences among the groups were evaluated using ² tests or one-way analysis of variance as appropriate; Scheffé’s F test was used for post hoc comparisons. P < 0.05 was considered statistically significant. Data are expressed as percent or mean ± SD.

	Results

Top Abstract Introduction Methods Results Discussion Appendix A Appendix B Appendix C References

 
Among the 154 patients we approached, 150 agreed to the interview. Two patients did not finish the interview because they found the psychological tests burdensome. We thus included 148 patients in our final analysis; similar numbers were assigned to each randomized group, and every interviewer conducted similar numbers of interviews for each group (Control, Risk, and Pain; Fig. 1). No interviewer reported that patients were suspicious about the real nature of the trial; in contrast, interviewers reported that most patients were surprised to hear about the deceptive nature of the trial during the debriefing. A few patients were initially distressed after hearing that no actual study would be performed, but most appreciated the importance of the study once our purpose was explained to them.

View larger version (23K): [in this window] [in a new window]   Figure 1. Trial profile.

Fifteen percent of the patients reported feeling that the interviewer pressured them to participate, and none of them agreed to participate. Only 8% of the patients reported that the interviewer increased their anxiety, and none consented to the proposed study. Group assignment, demographic characteristics, or type of operation did not influence the rate of patients who felt coercion. However, among those patients who felt coercion, there was a more frequent rate of depression (32% versus 14%; P = 0.079), and significantly more patients had low Internality scores (62% versus 16%; P = 0.02). Consent rates and understanding were similar in the patients who completed the HADS and IPC forms and in those who did not.

Demographic characteristics did not influence understanding of the risk or pain levels associated with the presented protocols, nor did anxiety or depression. Educational level between the groups did not differ significantly; however, the least educated patients tended to misunderstand the extent of risk or pain (P = 0.086). In contrast, IPC had a significant influence; understanding was compromised in patients having low Internality or high external Power scores (P = 0.022 and 0.048, respectively; Table 2).

	Discussion

Top Abstract Introduction Methods Results Discussion Appendix A Appendix B Appendix C References

We do not know how patients processed the information or whether they really perceived the implications of the risks. Patients tend to misinterpret the risks of research participation. This therapeutic misconception implies that patients deny the possibility of disadvantages from participation in clinical research (14). Additionally, according to Kass et al. (15), "patients assume that research into which they enter is safe. They assume that someone else has scrutinized the risks and benefits on their behalf." In contrast, our patients showed a high degree of altruism, believing that participation would increase knowledge, improve society, and help develop new treatments. Others have also shown that consenting subjects are altruistic R3-118397 R12-118397 R16-118397 (3,12,16,17). Although many of our patients expressed a sense of obligation to the interviewer, few believed that their care would be compromised by failure to participate. It thus seems that patients who knowingly agreed to participate in risky or painful protocols did so altruistically rather than under duress.

Evidence-based medicine is increasing the basis for clinical practice. Lately, placebo-controlled trials and sham surgery have been heavily discussed. On the basis of our results, further studies are required to learn about patients’ willingness to accept risks on behalf of scientific goals. Additionally, we need to learn more about risk perception to ensure that those patients definitely process information they receive.

Despite our attempt to optimize understanding, approximately 30% of the patients presented with each proposed study failed to identify the associated degree of risk or pain. A striking finding was that patients who did not mark the appropriate risk or pain level associated with the proposed protocols were only half as likely to consent. This finding is consistent with Epstein and Lasagna (13) who found that better understanding improved consent rates in healthy subjects. The results of Fetting et al. (18) also suggest that understanding increases the willingness to receive an experimental treatment. A consequence of the small consent rate in patients who misunderstood the consequences of participation is that only 9% of our patients unknowingly agreed to participate in a protocol involving considerable risk or pain. Our results suggest that increasing patients’ understanding does protect their best interests and will augment consent rates, even for protocols involving substantial risk or pain.

Even though length and readability of the risk paragraphs differed, understanding was similar in all groups. Therefore, it is important to identify other factors likely to influence understanding. Although educational level was not a statistically significant factor, the least educated patients had the poorest understanding (48% of patients with low education misunderstood). However, 36% of our patients with more than 13 years of schooling also failed to understand the risk or pain level. Therefore, restricting study enrollment to patients with medium or high educational levels is unlikely to assure adequate understanding.

People having low Internality or high external Power scores on the IPC scale do not believe they are in control of their lives but that external forces control them. These patients were significantly less likely to understand the presented protocols and were much more likely to feel coerced. A possible explanation is that they do not listen carefully or do not fully process the presented information because they do not expect their decisions to influence outcome. Lavelle-Jones et al. (19) reported similar results. Unfortunately, the IPC test would be difficult to integrate into the consent routine; it is thus unlikely that this test could be used to protect patients at high risk of misunderstanding critical protocol details.

We considered evaluating the consent process in patients being presented real studies. However, the protocols for actual studies with various risk and pain levels differ substantially, which would be a major confounding factor. They also have different inclusion criteria, which would preclude randomized assignment to one of the three risk/pain levels. More importantly, we needed to include blunt language exaggerating the risks and pain associated with two of the protocols and minimizing them in the control group. As hypothetical decisions do not accurately reflect results of authentic settings (20), we designed sham protocols and used a deceptive trial to achieve a setting as authentic as possible.

Sham study designs such as ours have been used in patients (21) and are frequently used in psychological studies. Ethicists generally agree that there are three conditions under which it is acceptable to use deception in clinical research R22-118397 (22,23): (a) if revealing the actual study purpose would destroy the major outcome, (b) if no unpleasant emotional experiences or physical risks are involved, and (c) if the deception is explained to the participants at the earliest practical opportunity.

Deceptive studies per se do not distress research subjects (20). Although a certain degree of stress is unavoidable in preoperative patients, we excluded those at special risk (i.e., those with cancer or scheduled for serious operations). We obtained consent from patients who agreed to be interviewed and consider participation in a clinical trial. We also emphasized that they were free to withdraw from the interview at any time. Finally, we fully debriefed the participants immediately after the study and explained our goal of improving the consent process to better protect participants in clinical research. Our study thus met all three criteria for ethical sham research.

To have a patient’s own and direct response to the risks presented, we gave patients only a few minutes to decide whether or not to participate and did not allow them to consult others. It has been reported that patients are best informed immediately after signing the consent forms (19). Therefore, we chose a quick and fairly simple measure of understanding. We are aware that patients might have marked the correct statement by chance or just remembered certain words. Others might have understood correctly but have drawn different conclusions than we intended. However, we believe that our immediate and simple measure closely reflects patients’ perception of the proposed risks at the decision-making time.

We evaluated a single patient population of limited size. It is very likely that our results would differ in cancer patients, in patients with especially serious diagnosis, or in patients with different cultural backgrounds. Five investigators conducted all the interviews. This number is too small to evaluate the independent effects of interviewer age, sex, research experience, or personality.

In summary, this is the first randomized trial to quantify the influence of risk and discomfort or pain on patients’ willingness to participate in clinical studies. The consent process protected patients, although not for the expected reason. Understanding was poor, but patients who failed to understand the risks or discomforts rarely consented. Furthermore, patients who felt pressured did not consent. Consequently, relatively few patients unknowingly agreed to participate in risky or painful studies. In contrast, patients who understand the risks involved are twice as likely to consent. Additionally, patients are willing to participate in risky or painful studies, apparently for altruistic reasons.

	Appendix A

Top Abstract Introduction Methods Results Discussion Appendix A Appendix B Appendix C References

 
Informed Consent Form for the Control Group
This study will test whether extra oxygen during and immediately after surgery reduces the risk of surgical wound infections and reduces the duration of hospitalization.

1) If I agree to participate in this study, the following things will happen:

a) I will be randomly assigned to one of the following groups:

Group A (Control Group): I will be given a routine amount of oxygen (30%) during surgery and during the first 2 hr after surgery by a face mask.

Group B (Treatment Group): I will be given extra oxygen (80%) during surgery and during the first 2 hr after surgery by a face mask.

b) A physician of the study group will inspect my surgical incision every day throughout hospitalization. This is only a visual inspection and not painful or risky.

2) This study will not interfere with my operation or therapy. All procedures of the study are covered by an insurance company.

3) I was consented by an investigator who has answered all my questions. If I have any further questions about this study, I can call 40400-XXXX.

4) Participation in research is voluntary. I am thus free to decline participation or withdraw from the study at any time. Doing so will not influence my care.

Risks and Side Effects
It has been proven that extra oxygen is harmless and the wound evaluations are painless. This study thus poses essentially no risk and will not produce any significant discomfort.

	Appendix B

Top Abstract Introduction Methods Results Discussion Appendix A Appendix B Appendix C References

 
Informed Consent Form for the Pain Group
This study will test whether extra oxygen during and immediately after surgery reduces the risk of surgical wound infections and reduces the duration of hospitalization.

1) If I agree to participate in this study, the following things will happen:

a) I will be randomly assigned to one of the following groups:

Group A (Control Group): I will be given a routine amount of oxygen (30%) during surgery and during the first 2 hr after surgery by a face mask.

Group B (Treatment Group): I will be given extra oxygen (80%) during surgery and during the first 2 hr after surgery by a face mask.

b) My temperature will be taken regularly during anesthesia and while I am in the postanesthesia care unit.

c) After the induction of anesthesia, a sterile plastic tube will be inserted into the skin of my upper arm. This tube is required to perform measurements of tissue oxygenation during and after the operation. It will be removed after the first 4 hr of recovery. At the end of the operation, the surgeon will insert a Teflon tube into the skin near my surgical incision. This tube measures growth of collagen fibers. This tube will be removed after 7 days. This tube will cause pain that will only slowly resolve over a period of a week.

d) On the first day after surgery, I will be taken to the Department of Radiology where I will have a computer tomography and a radiograph of my lungs, which usually take 30 min. I will still have surgical pain; consequently, being moved to the hard table can be painful. Most patients find this experience to be quite uncomfortable.

e) On the first day after surgery, my lung function will also be tested. This test involves removing a sample of blood from an artery in my wrist. This is far more painful than a typical venous blood sample because arteries are very sensitive.

f) A physician of the study group will inspect my surgical incision every day throughout hospitalization. This will require removing the dressing, which is usually uncomfortable. The inspection procedure itself is painful because it will require pressing on my surgical wound. Furthermore, I will need to stay in my bed throughout the 1-hr inspection.

2) This study will not interfere with my operation or therapy. All procedures of the study are covered by an insurance company.

3) I was consented by an investigator who has answered all my questions. If I have any further questions about this study, I can call 40400-XXXX.

4) Participation in research is voluntary. I am thus free to decline participation or withdraw from the study at any time. Doing so will not influence my care.

Risks and Side Effects
Extra oxygen is entirely harmless; furthermore, the proposed procedures are harmless and risk free. However, the tests that will be performed for this study are all painful. Daily inspections of surgical wounds require removing the dressing and pressing on my incision, which will be painful. The plastic tubes inserted into my arm and near my incision are harmless but can be painful for some hours. Being moved to the Radiology Department will be especially uncomfortable because I will have to remain still on a hard table. Obtaining the sample of blood from an artery in my wrist is painful. This pain can last several days.

	Appendix C

Top Abstract Introduction Methods Results Discussion Appendix A Appendix B Appendix C References

 
Informed Consent Form for the Risk Group
This study will test whether extra oxygen during and immediately after surgery reduces the risk of surgical wound infections and reduces the duration of hospitalization.

1) If I agree to participate in this study, the following things will happen:

a) I will be randomly assigned to one of the following groups:

Group A (Control Group): I will be given a routine amount of oxygen (30%) during surgery and during the first 2 hr after surgery by a face mask.

Group B (Treatment Group): I will be given extra oxygen (80%) during surgery and during the first 2 hr after surgery by a face mask. Extra oxygen might cause collapse of the lungs. If that happens, I will need to be connected to a breathing machine. I may also need a small operation to open my collapsed lungs. Both treatments are likely to increase the amount of time I need to stay in the hospital.

b) After the induction of anesthesia, a sterile plastic tube will be inserted into the skin of my upper arm. This tube is required to perform measurements of tissue oxygenation during and after the operation. It will be removed after the first 4 hr of recovery. This tube almost always causes bleeding under the skin that results in a bruise. Such bruises usually take 2 wk to resolve. There is also a substantial risk of infection. If I get an infection, I will need an operation to remove the infected bruise.

c) At the end of the operation, the surgeon will insert a Teflon tube into the skin near my surgical incision. This tube measures growth of collagen fibers. This tube will be removed after 7 days. There is also a substantial risk of infection whenever a foreign object is left inside the body for such a long time. If I get an infection, I will need IV antibiotics and will have to stay in the hospital for up to a week longer than usual.

d) On the first day after surgery, I will be taken to the Department of Radiology where I will have a computer tomography and a radiograph of my lungs, which usually take 30 min. The test involves quite a large exposure to radiation (approximately the amount I would normally get in 5 yr). Radiation exposure in general is clearly linked to cancer, problems with vision, and infertility.

e) On the first day after surgery, my lung function will also be tested. This test involves removing a sample of blood from an artery in my wrist. This procedure might damage the vessel, and full recovery often requires several days. In some cases, an emergency operation is required to fix the vessel and prevent permanent and serious injury to my fingers.

f) A physician of the study group will inspect my surgical incision every day throughout hospitalization.

2) This study will not interfere with my operation or therapy. All procedures of the study are covered by an insurance company.

3) I was consented by an investigator who has answered all my questions. If I have any further questions about this study, I can call 40400-XXXX.

4) Participation in research is voluntary. I am thus free to decline participation or withdraw from the study at any time. Doing so will not influence my care.

Risks and Side Effects
The extra oxygen that will be given, as part of this study, is potentially dangerous and may cause collapse of my lungs. If that happens, I will need to be connected to a breathing machine and stay at the intensive care unit. This is risky because it might lead to pneumonia and dysfunction of other organs. The tubes that will be inserted in my arm and near my incision will cause bruising. They may also cause tissue damage, which could require surgery, or an infection that would require antibiotic treatment and an extra week of hospitalization. The special radiograph-scan the day after surgery will expose me to radiation. The general risks of radiation exposure include: cancer, vision problems, and infertility. Sampling blood from my artery may cause substantial damage to the vessel; an operation may be required to repair this vessel and prevent permanent injury to my fingers.

	Acknowledgments

 
Supported, in part, by NIH Grant GM49670 (Bethesda, MD), the Joseph Drown Foundation (Los Angeles, CA), the Austrian National Bank Foundation (Vienna, Austria), and the Commonwealth of Kentucky Research Challenge Trust Fund (Louisville, KY).

	References

Top Abstract Introduction Methods Results Discussion Appendix A Appendix B Appendix C References

 

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