Heated-Hand Boxes for Obtaining "Arterialized"-Venous Blood

Shown above is a heated-hand box in use during a euglycemic hyperinsulinemic clamp

  Background:

A reference list is provided at the bottom for the technique of warming the hand to obtain "arterialized"-venous blood. As can be seen from this reference list, the technique has been used for a number of years.

The standard method of obtaining serial arterial blood samples is via catheter placement into an artery. For most routine clinical research studies, placement of an arterial line in the radial or femoral artery provides an unnecessary risk and unnecessary discomfort to the volunteer. The purpose of obtaining arterial blood is to obtain either (i) blood coming directly from the heart and lungs to measure oxygenation or (ii) to measure metabolite concentrations in the whole body. The former technique is still best done via direct arterial sampling, but the latter may be performed in other ways.

When blood passes through an organ bed (e.g. the liver or muscle), the organ will both extract and add metabolites to the blood. A common example is the removal of glucose and oxygen and addition of end-products of metabolism, lactate, CO₂, alanine, ..., as blood passes through muscle beds. Thus, the venous concentration of glucose will almost always be lower in the antecubital vein compared to the brachial artery. Hormones, such as epineprhine, are also extracted passing through tissues. For example, antecubital venous blood will have an epinephrine concentration of almost 1/2 that of arterial blood due to extraction of catecholamines across muscle. To obtain a measure of metabolite and hormone concentration in the whole body, blood coming directly out of the heart needs to be obtained.

Although we sweat to reduce our body temperature through evaporative loss of heat, we also have a physiological mechanism to open up capillaries to increase blood flow through the skin and remove heat directly through conduction and radiation. The hand is designed to cool itself primarily through opening up capillary beds. This mechanism also cools the hand by providing cooler blood when the hand temperature rises above 37°C -- thus, the principal of heating the hand to obtain "arterialized" blood. We say "arterialized" instead of "arterial" to differentiate that the venous effluent from a hand that has been warmed is not true arterial blood--only a good representation of it. The key element to obtaining "arterialized" blood from the vein of the hand is to get the skin temperature of the hand well above 37°C. The hand can be warmed in a variety of ways: placing in warm water, wrapping with a heating blanket, or warming by a gentle stream of heated air. We have chosen the latter approach as being the simplest, cleanest, and easiest way to warm the hand, sample blood from the hand, and see the hand during the process.

Dr. Matthews has been using the boxes that generate warm air to heat hands for clinical research studies since the early 1980's. The earliest boxes were simple and made from plywood and economical parts found in cheap space-heaters used to warm feet under the desk in an office. In the early 1990's Dr. Matthews designed the first box to meet (and exceed) the requirements for the Biomedical Engineering Dept at the New York Hospital (now the New York-Presbyterian Hospital). The box that was devised is shown in the photo above. Since that time, many copies of this box have been built and shipped around the country and world for use by other clinical investigators and in clinical research centers.

  Features:

• The box is entirely made of plexiglass with a few electronic and electrical components.
• It is completely clear, and all components and the patient's hand is visible.
• The hand is placed in a cavity through which heated air circulates to warm the hand.
• The insert where the hand is placed is on a slide and removes from the box for cleaning. Access to the inside of the box is gained for further cleaning, if necessary, when the insert is removed.
• The insert is sufficiently large for a second person to insert their hand also into the box to manipulate the catheter without having to remove the subject's hand from the box.
• We provide this box only for research purposes and are not a commercial concern. Thus, we do not, nor plan to seek a UL label for this box. However, the box is both grounded and electrically isolated (via the plexiglass) to negate any possibility of shock hazard.
• The air is heated by a heating plate. A small fan blows air up over the heating plate and down through the top of the box insert. A temperature transducer is placed just above the insert to monitor the air temperature above the hand.
• The air temperature is kept constant using a solid-state controller to regulate the current to the heating plate via a feedback circuit. The temperature controller can be adjusted to a range of temperatures in 1°C increments. The controller has built-in circuitry to shut off if the temperature sensor fails to provide a correct value (i.e. is disconnected or breaks). The temperature controller provides a digital display of the air temperature in the box.
• Boxes are sold to clinical investigators and institutions "as is". No claims are made about the boxes or their use.
• This box has been used in a variety of circumstances over the last 10 years. During the past 5 years, these boxes have been used to complete over 500 euglycemic-hyperinsulinemic clamps at the Clinical Research Center at the University of Vermont. Hands of patients of all ages have been placed continuously in the boxes for periods typically of 4 hours for these studies. There have been no burns of the skin reported from any of these studies.

  Operating Conditions:

• It takes about 15 minutes for the box to reach normal operating temperature once turned on.
• Normal operating temperature is recommended to be 50°C for extended placement of the hand in the box. Extended placement means continuously in the box. The box was designed for placement of the hand continuously in the box for periods of time from 2-6 hours, as often occurs during metabolic studies where the hand needs to be warmed prior to and during a euglycemic multi-step clamp with insulin infusion.
• For intermittent sampling where the hand will be in, then out of the box, an air temperature of 55°C is recommended. Under these conditions, the hand should be placed in the box for at least 10 minutes prior to sampling. After sampling, the hand is removed from the box.
• Although you will see a variety of reports in the scientific literature stating that the hands in the study were warmed to 60°C or higher to obtain arterialized-blood, we strongly discourage use of these temperatures. It is likely that in those studies, the 60+°C temperatures reported refer to the temperature of the air next to the heat source and not at the hand, as measured in our box.
• The photo above shows a box in "action": the box is designed to sit next to the patient on a standard hospital bed. Towels can be placed under the box or patient's arm to accommodate any bed or patient position.
• The sampling is done by placement of a catheter in a hand vein retrograde.

  Ordering Instructions:

• Contact Dwight Matthews, Ph.D. for current pricing and availability.
• Boxes are shipped and an invoice is generated.
• Because we are not a company nor make a profit, we do not have any mechanism for billing. Thus, prompt payment of the invoice is expected.

  Technical Points:

Measurement of the Skin Temperature of Two People As A Function Of Time After the Hand Was Placed In the Heated-Hand Box

Measurement of Oxygen Content of "Arterialized"-Blood Taken from One Subject As A Function Of Time After the Hand Was Placed In the Heated-Hand Box

Measurement of Arterial, Venous and "Arterialized-Venous" Plasma Epinephrine Concentration During Infusion of Epinephrine in Humans

REFERENCES:

1. WE Clutter, DM Bier , SD Shah & PE Cryer: Epinephrine plasma metabolic clearance rates and physiologic thresholds for metabolic and hemodynamic actions in man. J. Clin. Invest. 66: 94-101, 1980.
2. JD Best & JB Halter: Release and clearance rates of epinephrine in man: Importance of arterial measurements. J. Clin. Endocrinol. Metab. 55: 263-268, 1982.
3. DE Matthews, G Pesola & RG Campbell: Effect of epinephrine upon amino acid and energy metabolism in humans. Am. J. Physiol. Endocrinol. Metab. 258: E948-E956, 1990.

  Partial List of Locations Where Our Heated-Hand Box Is Used:

• Clinical Research Center, University of Vermont
• Department of Kinesiology, Arizona State University, Tempe AZ
• Clinical Research Center, University of California San Francisco, San Francisco, CA
• Mt. Zion Diabetes Research Center, University of California San Francisco, San Francisco, CA
• San Francisco General Hospital, University of California San Francisco, San Francisco, CA
• Clinical Research Center, Harbor General Hospital, UCLA, Torrance, CA
• City of Hope Medical Center, Duarte, CA
• Abbot Diabetes Care, Alamada, CA
• Clinical Research Center, University of Washington, Seattle, WA
• VA Puget Sound Health Care System, University of Washington, Seattle, WA
• Charles River Laboratories, Tacoma, WA
• Clinical Research Center, University of Alabama School of Medicine, Birmingham, AL
• University of Arkansas for Medical Sciences, Little Rock, AK
• John L. McClellan VA Medical Center, University of Arkansas for Medical Sciences, Little Rock, AK
• USDA Children's Nutrition Research Center, Baylor Medical College, Houston, TX
• Texas Children's Hospital, Houston, TX
• Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, LA
• Clinical Research Center, Washington University School of Medicine, St. Louis, MO
• Dept. of Pediatrics, Washington University School of Medicine, St. Louis, MO
• Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, MO
• Kinesiology and Health Education, Southern Illinois University Edwardsville, Edwardsville, IL
• Northwestern University, Chicago, IL
• Clinical Research Center, University of Michigan Medical Center, Ann Arbor, MI
• Ohio State University, Columbus, OH
• Ross Products, Abbot Laboratories, Columbus, OH
• Duke Center for Living, Duke University, Durham, NC
• Clinical Research Center, Wake Forest University Medical Center, Winston-Salem, NC
• Human Performance Laboratory, East Carolina University, Greenville, NC
• Clinical Research Center, Georgetown University Medical Center, Washington, DC
• ASTRA Unit, National Institutes of Health, Harbor Hospital,Baltimore, MD
• Clinical Research Center, Johns Hopkins Bayview Medical Center, Baltimore, MD
• Clinical Research Center, Bristol-Myers Squibb, Hamilton, NJ
• Clinical Research Center, Rochester University Medical Center, Rochester, NY
• University of Syracuse, Syracuse, NY
• Clinical Research Center, The Rockefeller University, NYC
• Clinical Research Center, Weill Medical College, Cornell University, New York Hospital, NYC
• Citigroup Biomedical Imaging Center, Weill Medical College, Cornell University, New York Hospital, NYC
• St. Luke's-Roosevelt Hospitals, Columbia University, New York, NYC
• Clinical Research Center, Albert Einstein College of Medicine, Bronx, NYC
• John B. Pierce Laboratory, Yale University, New Haven, CT
• Brigham and Women's Hospital, Boston, MA
• Clinical Research Center, Beth Isreal Deaconess Medical Center, Boston, MA
• USDA Human Nutrition Research Center for Aging,Tufts University, Boston, MA
• Tropical Medicine Research Institute, University of the West Indies, Jamaica
• Wellcome Clinical Research Facility, Queen Elizabeth Hospital, Birmingham, England
• Diabetes & Endocrinology Dept., Postgraduate Medical School, University of Surrey, Manor Park, England
• Clinical Pharmacology Europe, Merck & Co., Brussels, Belgium
• University of Vienna, Vienna, Austria
• Glucon Medical Ltd., Petach Tikva, Israel
• Kinderklinik, Inselspital, Bern, Switzerland
• Nestlé Research Center, Lausanne, Switzerland
• Dept. of Surgery, Auckland City Hospital, University of Auckland, Auckland, New Zealand

  References from the Literature about "Arterialized"-Venous Blood Sampling:

1. EAH McGuire, JH Helderman, JD Tobin, R Andres & M Berman: Effects of arterial versus venous sampling on analysis of glucose kinetics in man. J. Appl. Physiol. 41: 565-573, 1976.
2. NN Abumrad, D Rabin , MP Diamond & WW Lacy: Use of a heated superficial hand vein as an alternative site for the measurement of amino acid concentrations and for the study of glucose and alanine kinetics in man. Metabolism 30: 936-940, 1981.
3. GE Sonnenberg & U Keller: Sampling of arterilized heated-handvenous blood as a nonivasive technique for the study of ketone body kinetics in man. Metabolism 31: 1-5, 1982.
4. A Astrup, L Simonsen, J Bülow & NJ Christensen: Measurement of forearm oxygen consumption: Role of heating the contralateral hand. Am. J. Physiol. Endocrinol. Metab. 255: E572-E578, 1988.
5. DC Brooks, PR Black , MA Arcangeli, TT Aoki & DW Wilmore: The heated dorsal hand vein: An alternative arterial sampling site. JPEN J. Parenter. Enteral Nutr. 13: 102-105, 1989.
6. IW Gallen & IA Macdonald: Effect of two methods of hand heating on body temperature, forearm blood flow, and deep venous oxygen saturation. Am. J. Physiol. Endocrinol. Metab. 259: E639-E643, 1990.
7. JH Green, FR Ellis, TM Shallcross & PN Bramley: Invalidity of hand heating as a method to arterialize venous blood. Clin. Chem. 36: 719-722, 1990.
8. GA Zello, JM Smith, PB Pencharz & RO Ball: Development of a heating device for sampling arterialized venous blood from a hand vein. Ann. Clin. Biochem. 27: 366-372, 1990.
9. PN Bramley, RW Heighton & JH Green: Methodological considerations in arterialization of venous blood. Clin. Chem. 37: 1139-1140, 1991.
10. MD Jensen & VJ Heiling: Heated hand vein blood is satisfactory for measurements during free fatty acid kinetic studies. Metabolism 40: 406-409, 1991.
11. KC Copeland, FA Kenney & KS Nair: Heated dorsal hand vein sampling for metabolic studies: A reappraisal. Am. J. Physiol. Endocrinol. Metab. 263: E1010-E1014, 1992.
12. KN Frayn & IA Macdonald: Methodological considerations in arterialization of venous blood. Clin. Chem. 38: 316-317, 1992.
13. JC Marker, PE Cryer & WE Clutter: Simplified measurement of norepinephrine kinetics: Application to studies of aging and exercise training. Am. J. Physiol. Endocrinol. Metab. 267: E380-E387, 1994.
14. A Kurpad & M Elia: Effect of repeated hand warming in metabolic studies. Med. Sci. Res. 23: 51-52, 1995.