Participating in clincal research is voluntary. The following information in pdf form provides further information from the UCSF Committee on Human Research, as well as the Human Subjects Bill of Rights.
Volunteer subjects cannot partipicate if the following apply to them:
Subjects are exluded from the Methemoglobin study if the following apply to them:
Subjects should reconsider if they:
The first step of the study is placing a small (22 G) catheter in the artery of one wrist. This is done using local anesthesia to minimize the discomfort. Subject's will then have pulse oximeters attached to fingers, sometimes ear lobes, occasionally toes. These are attached as a small clip or bandaid that goes over the nailbed. Thse insturments shine a light through the finger. Attachement and removal involves no discomfort. Subject will have a nose clip placed on either side of the nostrils, so that he/she is forced to breathe through the mouth. Subject will then breathe a special gas mixture through a moutpiece. The mouthpiece is similar to what is used on a snorkel.
Subjects will be asked to breathe regularly, but more deeply and somewhat faster than normal as the gas mixture is adjusted to lower levels of oxygen. Blood samples are removed from the catheter in the artery at various time points. This does not involved further invsive proceudres. Each "run" involves 8-10 samples, takes about 15 minutes, and finishes when the subject breathees oxygen. A comlete study consist of 2-3 "runs" depending on the number of samples. The catheter in the wrist is removed at the end of the study, and pressure is held on the puncture site for 10 minutes. Subjects are then free to leave. Normal activites are fine, but vigours activity of the arm where the catheter was placed should be avoided for several hours.
It is necessary to sign a consent for the study. You can download a pdf of the consent ahead of time, which should be read ahead of time, so that we can take time to answer any questions.
This study is different from our standard pulse-ox studies in that we’re testing devices that detect methemoglobin (met-Hb). This study would require around 2.5 to 3 hours of your time, and it pays $200. Similar to the pulse oximeter study, an 22 gauge arterial catheter is placed using local anesthesia to minimize discomfort. An iv catheter (20 or 22 gauge) is also place for this study, using local anesthesia. To induce the formation of met-Hb in our study, a slow infusion of sodium nitrate is given via an intravenous line. Sodium nitrite oxidizes normal hemoglobin present in red blood cells into a useless form of hemoglobin called methemoglobin. The nitrite infusion will slowly increase met-Hb in the blood from a normal level of .1%-1% to about 13%-15%. This process will take anywhere from 1.5 to 2 hours. We stop our infusion when blood levels reach 9%, after which the remaining nitrite brings the final level to the 12%-14% mark. Levels of methemoglobin in excess of 20% may cause fatigue, headache, exercise intolerance, dizziness, and mental status changes, but these symptoms are very rarely observed in healthy, normal individuals at levels less than 20%. Blood samples will be periodically drawn from an arterial line and analyzed in a co-oximeter, much like our usual pulse-ox studies. Upon initial infusion of the nitrite, your body already begins to metabolize methemoglobin back to normal, useful hemoglobin; however, it may take several hours for methemoglobin to drop to pre-study levels, so strenuous exercise immediately after the study is discouraged for a few hours.
It is necessary to sign a consent for the study. You can download a pdf of the consent ahead of time, which should be read ahead of time, so that we can take time to answer any questions.
Carboxyhemoglobin is a complex formed by the binding of carbon monoxide and hemoglobin. This complex is formed in the human body when cabrbon monoxide is inhaled, most commonly from tobacco smoke. The formation of this complex can hinder the delivery of oxygen to your tissues.
In our study, you will be given a very small, safe dose of carbon monoxide to inhale which will increase your carboxyhemoglobin levels to around 10%, approximately equivalent to smoking a pack of cigarettes. Throughout the study, we will periodically take 1cc sized blood samples from an arterial line which we will analyze in a co-oximeter machine. Those results will be compared with the results of a non-invasive oximeter, helping to determine it's accuracy. Once we reach 10% carboxyhemoglobin levels, the subject will complete a round of hypoxia, similar to our standard pulse oximeter studies. The subject will breathe a special mixture of gasses which will be adjusted to bring you oxygen saturation levels down to as low as 80%. 1cc sized blood samples will be taken at each level of oxygen desaturation.
After the completion of the study, it will take between 4-6 hours for the carbon monoxide to leave your system so it is recommended that you not participate in any strenuous activity immediately after. Some possible side effects include fatigue, or a feeling of light headedness. We will have pure oxygen on hand to reverse the effects if you feel any of those symptoms.
It is necessary to sign a consent for the study. You can download a pdf of the consent ahead of time, which should be read ahead of time, so that we can take time to answer any questions.
In this study we will be studying the accuracy of cerebral oximeters (devices that detect brain oxygen levels by shining light through the forehead) in the pressence of hypoxia. In addition to hypoxia you could either be exposed to increased levels of methemoglobin or carboxyhemoglobin but never both. It will be specified in the recruitment email whether or not increased methemoglobin or carboxyhemoglobin will be used. The levels of each substance will be equivalent to those reached in the methemoglobin or carboxyhemoglobin studies mentioned above.
For this study, you will have an arterial catheter inserted into one of your wrist arteries under local anesthesia. Also an intravenous catheter will be placed in a vein in your hand. Lastly, a small catheter will be inserted into one of your jugular veins in your neck to enable blood samples to be drawn.
You will first be asked to breathe through a mouth piece with a nose clip on your nose. A special mixture of gasses will be adjusted to bring your blood oxgygen saturation levels down to as low as 80% over a series of plateaus. Two blood samples will be taken from the arterial catheter and two will be taken from the jugular catheter at each plateau. Each sample will be approximately 1cc. The subject will briefly be given %100 oxygen to restore normal oxygen saturation levels at the end of each run of desaturation.
If carboxyhemoglobin or methemoglobin are being used in the study the subject will then either be asked to breathe small amounts of carbon monoxide or receive an intravenous dose of sodium nitrite to induce the formation of carboxyhemoglobin and methemoglobin repectively. This will be done in the same manner described above for the methemoglobin and carboxyhemoglobin studies.
Once the proper levels of carboxyhemoglobin or methemoglobin are obtained a second run of oxygen desaturation ,identical to the first, will be performed. A second desaturtion run will also take place if caboxyhemoglobinemnia and methemoglobinemia are not induced.
After the completion of the study, it will take several hours for the carbon monoxide or methemoglobin to leave your system so it is recommended that you not participate in any strenuous activity immediately after. Some possible side effects include fatigue, nausea, or a feeling of light headedness.
It is necessary to sign a consent for the study. You can download a pdf of the consent ahead of time, which should be read ahead of time, so that we can take time to answer any questions.
At the initial screening and consent visit, after the subject has given consent, blood will be drawn to screen for anemia and hepatitis C. Ten milliliters or 2 teaspoons of blood will be drawn for these tests. A urine pregnancy test will be performed on female volunteers. An Allen’s test will be performed to assess the adequacy of collateral circulation in the hand on the side used for arterial cannulation.
On the experimental day, each volunteer will undergo hemodilution. An intravenous catheter will be placed in each arm using local anesthesia. A 22-gauge radial arterial catheter will be placed with local anesthesia for direct measurement of blood pressure and sampling of arterial blood. Standard pulse oximetry, invasive arterial pressure waveform, and electrocardiogram will be monitored continuously. These monitors provide continuous displays of blood pressure and heart rate, with alarms for tachycardia and hypotension. Blood will be withdrawn by gravity from one of the iv catheters into CPDA-1 bags. During withdrawal of these units, withdrawn volume will be replaced by simultaneous infusion of a volume of 5% Human Albuminequal to 1.1 times the volume withdrawn to maintain normovolemia (500 ml for each unit, which is 450 ml of whole blood). The withdrawn blood will be processed by the blood bank into packed red blood cells and plasma. The autologous plasma will be then be used in conjunction with 5% Human Albumin to replace withdrawn volume. Blood will not be withdrawn faster than 1 unit in 20 minutes, allowing for the subject to compensate physiologically. Blood will be removed to a target hemoglobin concentration no lower than 7 gm/dl. The goal is to avoid going lower than 7 gm/dl, because below this many subjects begin to experience more symptoms of anemia, although our previous studies involved hemodilution to target levels of 5 gm/dl.
The amount of blood removal necessary to achieve the target hemoglobin, can be calculated as follows:
Blood removed = Estimated Blood Volume • Ln (Hemoglobininitial/Hemoglobintarget)
(where estimated blood volume is 65 ml/kg for women, and 70 ml/kg in men). For example, a 60 kg women, with a starting hemoglobin of 12.5 gm/dl, would be expected reach a hemoglobin just under 8 gm/dl with 4 units of blood withdrawal.
During the study the following continuous monitoring and laboratory studies will be done:
Additional samples will be tested if the doctor feels it is necessary for monitoring of the volunteer, and for data collection for the primary end-point. Before transfusion and after each unit the heart rate, blood pressure, pulse oximeter saturation, and temperature will be recorded as in a usual transfusion procedure.
The physician doing the monitoring will document and record on paper the following items after each unit of blood removed or re-infused: HR, BP, O2 sat from a pulse oximeter, and symptoms of acute anemia (lightheaded or dizzy).
On some study days, changes in oxygen saturation will be induced by breathing 100% oxygen, or air/nitrogen mixtures to change oxygen saturation to no lower than 80% in the presence of anemia. This is necessary to test the accuracy of the pulse hemoglobin measurement in the presence of other hemoglobins (deoxyhemoglobin) which have the potential to affect the accuracy of the hemoglobin measurement. The degree of hypoxia that we will use will depend on the degree of anemia as follows: For a hemoglobin of 7 g/dl, a saturation of no lower than 90% will be used. For a hemoglobin of 8 g/dl, the lowest saturation would be 80%. These both result in about the same oxygen carrying capacity of blood (~9 ml/dl: saturation X gm Hb/dl X 1.39 ml O2/gm Hb). In no case will a saturation lower than 80% be used.
After reaching the target [Hb}, and following measurement, the subject’s autologous PRBC’s will be slowly re-infused. To accommodate the additional blood volume, the first 2 units will be infused of 1 hour, with 45 minutes for each additional units. All measurement will continue during the reinfusion of blood. The subject will be observed for an additional hour, and the iv catheters and arterial line will be removed.
The physician will be immediately available for emergencies. The subject will be allowed to return home accompanied by a friend or family member. Subjects will be called 48-72 hrs after the study and if they have any symptoms or concerns they will speak with a study MD who may request they return to UCSF to see them if any additional treatment is needed.
Study volunteers may choose to stop the study at any point.
It pays $75-$100 and takes approximately 1 hour.
It pays $200, and takes 2.5 to 3 hours.
It pays $150 and takes 2 to 2.5 hours.
It pays $300 and takes 2.5 to 3 hours.
It pays up to $350 if subject completes the full 8 hours of the study.
Carboxyhemoglobin study w/hypoxia with available slots at 8AM, 10AM, and 1PM for each day. The study takes 2 hours and pays $150 for you time.
Methemoglobin study w/hypoxia with available slots at 8AM, 10:30 AM, and 1PM. The study takes 2-2.5 hours and pays $300 for you time.
Paul Au
aupaul@anesthesia.ucsf.edu
Office 415-476-1412
Study Room 415 353 1431
Pablo Gabatto
gabattop@anesthesia.ucsf.edu
Office 415 476 8984
