Heated-Hand Boxes for Obtaining "Arterialized"-Venous Blood
A heated-hand box (HHB) shown in use during a euglycemic hyperinsulinemic clamp
These boxes are for sale (see below) to institutions and investigators performing clinical research requiring arterialized-venous blood.
A list of peer-reviewed publications concerning the technique is provided below. Details for the technique of warming the hand to obtain "arterialized"-venous blood are also shown. As can be seen from these publications, 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 catheter 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 epinephrine, 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.
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.
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.
Because we do not make a profit, we do not accept credit cards and have limited mechanisms for tracking down payments. Thus, prompt payment of the invoice by check or bank transfer is expected.
Measurement of the skin temperature of two people as a function of time after the hand was placed in the heated-hand box:
Each graph represents the time course of hand-skin temperature in one subject. A thermistor was placed directly on the back of the hand with a piece of tape, and the hand inserted into a box pre-heated to 60°C. The skin temperature immediately rose with heating. Opening of capillaries within the hand is seen by the rapid slowing of the rate of heating at about 2-3 minutes. Once "arterialized", the temperature of the skin remained relatively constant at ~45°C. From these data we recommend the lower 50°C setting for extended heating periods, as it allows a smaller gradient of temperature to keep the hand warm and arterialized.
Measurement of oxygen content of "arterialized-venous" blood taken as a function of time after the hand was placed in the eated-hand box:
The values on the left and symbols in red on the graph are pO2; the values on the right and symbols in blue are % O2 saturation.
Measurement of arterial, venous and "arterialized-venous" plasma epinephrine concentration during infusion of epinephrine in human subject:
This graph appears in the 1990 Matthews et al. paper and shows data from that work and data taken from the literature. The graph shows the large drop in plasma epinephrine concentration going from arterial to venous sampling (Best & Halter).
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.
JD Best & JB Halter: Release and clearance rates of epinephrine in man: Importance of arterial measurements. J. Clin. Endocrinol. Metab. 55: 263-268, 1982.
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.
List of Locations Where Our Heated-Hand Boxes Are Used:
Clinical Research Center, University of Vermont
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
Dept. of Nutrition, University of California Davis, Davis, CA
Diablo Clinical Research, Walnut Creek, CA
AMCR Institute, Escondido, CA
ProSciento, Inc., Chula Vista, CA
Clinical Research Center, Harbor General Hospital, UCLA, Torrance, CA
City of Hope Medical Center, Duarte, CA
Abbot Diabetes Care, Alamada, CA
VA San Diego, Univerity of California San Diego, San Diego, CA
Touro University California, Vallejo, CA
Clinical Research Center, University of Washington, Seattle, WA
VA Puget Sound, University of Washington, Seattle, WA
Rainier Clinical Research Center, Renton, WA
Charles River Laboratories, Tacoma, WA
Dept. of Kinesiology, Arizona State University, Tempe AZ
Cardiovascular Genetics, University of Utah, Salt Lake City, UT
University of Colorado Anschutz Medical School, Aurora, CO
Clinical & Translational Science Center, University of New Mexico Health Sciences Center, Albuquerque, NM
Dept. of Health and Kinesiology, Texas A&M University, College Station, TX
Endeavor Clinical Trials, San Antonio, TX
USDA Children's Nutrition Research Center, Baylor Medical College, Houston, TX
Texas Children's Hospital, Houston, TX
University of Arkansas for Medical Sciences, Little Rock, AR
Arkansas Children's Research Institute, Arkansas Children's Hospital,Little Rock, AR
John L. McClellan VA Medical Center, University of Arkansas for Medical Sciences, Little Rock, AR
Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, LA
Clinical Research Center, University of Alabama School of Medicine, Birmingham, AL
Clinical Drug Development Division, Comprehensive NeuroScience, Inc., Miramar, FL
Translational Research Institute for Metabolism and Diabetes, Burnham Medical Research Institute, Winter Park, FL
Atlanta Clinical & Translational Science Institute, Emory University School of Medicine, Atlanta, GA
Atlanta Diabetes Associates, Atlanta, GA
University of Kansas Medical Center, Fairway, KS
Institute for Clinical and Translational Science, University of Missouri School of Medicine, Columbia, MO
Clinical Research Center, University of Missouri School of Medicine, Columbia, MO
Center for Clinical Studies, 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
Dept. of Food Science & Human Nutrition, University of Illinois, Urbana, IL
Dept. of Kinesiology and Nutrition, University of Illinois, Chicago, IL
Northwestern University, Chicago, IL
Xeris Pharmaceuticals, Chicago, IL
Clinical Research Center, University of Michigan Medical Center, Ann Arbor, MI
Center for Clinical and Translational Science, University of Kentucky, Lexington, KY
Endocrinology Division, Ohio State University Wexner Medical Center, Columbus, OH
Ross Products, Abbot Laboratories, Columbus, OH
711th Human Performance Wing. Wright-Patterson AFB, Dayton, OH
Ohio University Heritage College of Osteopathic Medicine, Athens, OH
Duke Center for Living, Duke University, Durham, NC
Dept. of Nutrition, University of North Carolina, Chapel Hill, 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
National Institute of Alcohol Abuse & Alcoholism, NIH, Bethesda, MD
National Institute of Diabetes, Digestive & Kidney Diseases, NIH, Bethesda, MD
Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, Bethesda, MD
ASTRA Unit, National Institute of Aging, NIH, Harbor Hospital,Baltimore, MD
Clinical Research Center, Johns Hopkins Bayview Medical Center, Baltimore, MD
University of Maryland School of Medicine, Baltimore, MD
Baltimore VA Medical Center, Baltimore, MD
Clinical Research Center, Bristol-Myers Squibb, Hamilton, NJ
Smilow Center for Translational Research, University of Pennsylvania Perlman School of Medicine, Philadelphia, PA
Center for Human Phenomic Science, University of Pennsylvania Presbyterian Hospital, Philadelphia, PA
Penn Presbyterian Medical Center, Philadelphia, PA
Clinical Research Center, Rochester University Medical Center, Rochester, NY
University of Syracuse, Syracuse, NY
Clinical Research Center, The Rockefeller University, New York, NY
Clinical Research Center, Weill Medical College, Cornell University, New York Hospital, New York, NY
Citigroup Biomedical Imaging Center, Weill Medical College, Cornell University, New York Hospital, New York, NY
New York State Psychiatric Institute, Columbia University Medical Center, New York, NY
St. Luke's-Roosevelt Hospitals, Columbia University, New York, NY
Clinical Research Center, Albert Einstein College of Medicine, Bronx, New York, NY
Dept. of Anesthesiology, Stony Brook University Medicine, Stony Brook, NY
John B. Pierce Laboratory, Yale University, New Haven, CT
Boston Children's Hospital, Boston, MA
Brigham & Women's Hospital, Boston, MA
Clinical Research Center, Beth Israel Deaconess Medical Center, Boston, MA
Massachusetts General Hospital, Boston, MA
USDA Human Nutrition Research Center for Aging,Tufts University, Boston, MA
Newton Photonics, Inc., Chestnut Hill, MA
LMC ESD Inc., Toronto, Ontario, Canada
Dept. of Anesthesia, Royal Victoria Hospital, Montreal, Québec, Canada
Institute of Sports Medicine, Bispebjerg Hospital, Copenhagen, Denmark
HillerØd Hospital, HillerØd, Denmark
Dept. for Nutrition, Exercise and Sports, University of Copenhagen, Frederiksberg, Denmark
Dept. of Vascular Medicine, Academic Medical Center Amsterdam, Amsterdam, Netherlands
Dept. of Internal Medicine, Academic Medical Center Amsterdam, Amsterdam, Netherlands
Dept. of Endocrinology & Metabolism, Academic Medical Center Amsterdam, Amsterdam, Netherlands
Radboud University Nijmegen Medical Centre, Nijmegen, Netherlands
Centrum Medyczne OMEDICA, Poznan, Poland
University of Vienna, Vienna, Austria
Kinderklinik, Inselspital, Bern, Switzerland
Nestlé Research Center, Lausanne, Switzerland
Koçak Farma A.S., Istanbul, Turkey
Glucon Medical Ltd., Petach Tikva, Israel
Dept of Food Science and Nutrition, Agriculture College, King Saud University, Riyadh, Saudi Arabia
Synchron Research Services, Pvt. Ltd., Gujarat, India
Torrent Pharmaceuticals Ltd., Ahmedabad, India
Biomedical Sciences Institutes, National University of Singapore, Singapore
Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong
Baker IDI Heart & Diabetes Institute, Melbourne, Victoria, Australia
School of Exercise and Nutrition Sciences, Deakin University, Burwood, Australia
Dept. of Surgery, Auckland City Hospital, University of Auckland, Auckland, New Zealand
References from the Literature about "Arterialized"-Venous Blood Sampling:
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.
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.
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.
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.
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.
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.
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.
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.
PN Bramley, RW Heighton & JH Green: Methodological considerations in arterialization of venous blood. Clin. Chem. 37: 1139-1140, 1991.
MD Jensen & VJ Heiling: Heated hand vein blood is satisfactory for measurements during free fatty acid kinetic studies. Metabolism 40: 406-409, 1991.
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.
KN Frayn & IA Macdonald: Methodological considerations in arterialization of venous blood. Clin. Chem. 38: 316-317, 1992.
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.
A Kurpad & M Elia: Effect of repeated hand warming in metabolic studies. Med. Sci. Res. 23: 51-52, 1995.