Reduction of medical error has become a major focus of health care organizations. There have been abundant reports regarding the unacceptable medical error rate and associated monetary and social consequences. In November, 2010, the US Department of Health and Human Services released a study of errors associated with the care of Medicare recipients.1 The study indicated that 13.5% of Medicare patients experienced serious error resulting in harm that was defined as prolonged hospital stay, permanent harm, life-sustaining intervention, or death. According to the study, the estimated annual Medicare statistics for medical error are staggering: 1.6 million harmed and 180,000 deaths.2 Clearly, there is a great need to reduce the occurrence of medical errors. To this end, the AARC has pledged to meet two patient safety goals to be achieved by the end of 2013 as proposed by the Centers for Medicare and Medicaid Services (CMS). The goals are: 1. Decrease preventable hospital-acquired conditions by 40%; and 2. Reduce preventable complications during the transition from one care setting to another so that hospital readmissions would be reduced by 20%.3

The importance of blood gases in diagnostics and patient care cannot be understated. From determination of home oxygen need to care of the critically ill, blood gas results are central in health care decisions. Subsequently, any error in reporting blood gases can result in adverse consequences. Technology advancements have improved analytic error detection, with some analyzers having the ability to detect sensor and sample errors and the presence of interfering substances. This advanced analytic error detection ability can help reduce potential errors in diagnostics and treatment. The availability of expanded menus on today’s blood gas analyzers provides the ability to measure electrolytes, metabolites, and CO-Oximetry, greatly improving their usefulness. An increasing number of hospitals are recognizing the importance of the expanded blood gas analyzer menu in providing improved timeliness in the care of the critically ill.

New Challenges

The addition of nontraditional analytes to blood gas analyzers presents advantages and challenges. The advantages lie in the ability to quickly provide a more complete laboratory picture with single whole blood samples. The challenges are twofold: first, understanding the interrelationships of blood gases, electrolytes, metabolites, and CO-Oximetry; and second, sample handling considerations. Improper handling of samples can lead to significant preanalytic error. The wider range of analytes available with blood gases also increases the potential for preanalytic error, and the sample handling precautions. Indeed, the importance of preventing preanalytic error in blood gases is often overlooked. Numerous studies have reported that the majority of laboratory errors are preanalytic. For example, Plebani and Carraro3 reported that greater than 68% of errors in a university medical center were preanalytic in nature.

Samples that are acquired for blood gas analysis present a particular challenge to efforts aimed at limiting preanalytic change. Blood gas samples are whole blood; as such, the cells continue to metabolize after removal from the vascular system. Also, the very nature of the physiology associated with the primary analytes—pH, pCO2, and pO2—increases the importance of proper sample handling. Exposure to trapped air, icing, delayed analysis, and a host of other factors can significantly alter the reported values. Many of these same factors also can influence values reported for whole blood electrolytes, metabolites, and CO-Oximetry. Controlling preanalytic error helps assure that the blood gas and other values will reflect the condition of the patient when the blood was drawn and not changes that occurred from improper sample handling. Knowledge of preanalytic pitfalls and adherence to good handling practices can reduce potential adverse health care events that could result from preanalytic blood gas errors. The following recommendations can help reduce preanalytic error in blood gas/multianalyte results (see Table).

Common Preanalytic Errors

Air Entrapment. Air entrapment is probably one of the most common and most easily remedied sources of error in blood gas analysis. The major effect of exposure to air is alteration of pao2, with less pronounced changes in pH, pCO2 and ionized calcium (iCa). At sea level, the po2 of room air is approximately 150 mm Hg with a pCO2 approaching 0 mm Hg. Trapped air causes arterial po2 to move toward 150 mm Hg. Entrapped air has the potential to cause significant error in the reported pao2 and calculated oxygenation values. If the actual pao2 was less than 150 mm Hg, trapped air will result in false elevation of pao2. For a patient with an actual pao2 greater than that of room air, the reported pao2 will be falsely lowered. While not as marked, air exposure will cause a lowering of the paCO2 with a subsequent increase in pH. Ionized calcium is also affected by air exposure, secondary to the increase in pH. For each increase of 0.1 in pH, iCa will increase by approximately 0.036 mmol/L. Factors that affect the degree of error from air entrapment are numerous and include size of air bubble relative to syringe blood volume, length of time of air exposure, mixing/agitation, temperature (icing can accelerate po2 increase in plastic syringes), actual pao2 value, and Hbo2 saturation.

It should be noted that particular effort should be made to remove air bubbles in samples that are transported via pneumatic tube. During pneumatic tube transport, the rapid acceleration and deceleration agitates the sample and amplifies the error from bubble entrapment. Thus, it is critical to remove air bubbles as quickly as possible after the draw.

Improper Mixing. Mixing whole blood samples is important for proper heparin anticoagulation and to ensure accurate results, particularly if hemoglobin, hemoglobin derivatives, and hematocrit are being measured. For syringes, immediately after trapped air removal, gently mix sample for a minimum of 15 to 30 seconds in two planes using a “rock and roll” motion. The “rock and roll” motion prevents the potential for centrifugal concentration effect, which could cause errors in whole blood samples. If analysis is not immediate, remix the sample prior to analysis. A remix time of 1 minute is recommended if analysis is delayed by 5 minutes. Longer mix times should be used if samples analysis is delayed beyond 5 minutes. Care should be exercised in mixing to avoid mechanical hemolysis that could result from rapidly rotating the syringe against a ring. This is particularly true for iced samples, as icing increases red cell friability. Even a small amount of hemolysis can significantly increase potassium. It is also a good practice to expel the first few drops into a gauze pad prior to analysis as an aid in preventing microclots in the analyzer.

Capillary Tube Mixing. Capillary tubes are coated with dry heparin. After the sample is obtained and capped, the tube should be rolled between the palms for a minimum of 5 seconds in a horizontal plane. Alternatively, a metal flea and magnet can be used to mix the sample for a minimum of 5 seconds. Samples should be remixed if analysis is delayed, with longer remix times for prolonged delays.

Inappropriate Heparinization. Dry lyophilized lithium heparin is preferred for arterial blood gas sampling. Liquid sodium heparin preparations can alter pH, blood gas, and electrolyte values on “short draw” samples. A sample of 0.25 ml will be diluted by approximately 40% with liquid heparin that remains in the syringe dead space.

For electrolyte analysis, use dry lithium heparin in low concentration or balanced formulation. The anticoagulation effect of heparin consumes ionized calcium. Syringes having high concentrations of heparin can falsely reduce ionized calcium.5

Appropriate mixing is important for anticoagulation. A very small amount of heparin can effectively prevent coagulation. No amount of heparin can reverse clotting.

Metabolic Changes/Ice Slurry Storage. Blood cells continue metabolism post-draw, with RBCs producing lactate and H+ ions via lactate metabolism. White cells and thrombocytes consume O2 and glucose and produce CO2 and H+ via aerobic metabolism. Samples with high white cell counts (leukocythemia) can consume large amounts of O2 very rapidly, which can result in falsely decreased po2 values.

Icing slurry storage is used to reduce postdraw metabolism for anticipated delay in analysis. However, it must be understood that prolonged exposure to ice slurry of blood in plastic syringes can cause an increase in sample po2.

This is because plastic syringes are permeable to oxygen diffusion. Icing nearly doubles blood oxygen solubility and hemoglobin has increased affinity for oxygen at lower temperature. These factors cause oxygen loading of blood in iced plastic syringes. When the sample temperature is increased to 37°C in the blood gas analyzer, the additional O2 is released to the plasma yielding a falsely elevated po2.

The AARC Clinical Practice Guidelines suggest this: Samples that will be analyzed in less than 30 minutes do not need to be iced. If analysis will be delayed more than 30 minutes, samples should be placed in ice water slurry.6

Arterial Line Draw. Heparinized infusion lines are used to keep arterial and other vascular access lines patent. It is important to use an appropriate and consistent waste volume when using arterial lines, Swan-Ganz, or peripheral lines for blood gas/multianalyte sampling analysis. Two times the dead space should be used as the waste volume.7 This volume has been shown to reduce preanalytic error from flush solution without causing excessive blood loss. If vascular line dead space is unknown, turn the stopcock to the sampling port and withdraw flush solution until blood appears in hub of waste syringe. The volume in the syringe at that point will be equal to the dead space, double that volume for the waste draw.

Steady State. Ideally, blood gas samples should be obtained 20 to 30 minutes after oxygen, ventilator, or PEEP/CPAP changes. Some patients, such as those with severe COPD or significant V/Q mismatch, might have even longer equilibration times.

Temperature Correction. The practice of temperature correction, while not ordinarily considered a source of preanalytic error, should be mentioned. While there is some controversy with this practice, it is often not well understood by those who use it. In 1995, Barry Shapiro, MD, expressed some concerns with this practice in an article. He made three points: 1) Deviation from 37°C values demands deviation from well-documented guidelines for interpreting 37° values (there are no reference ranges at other temperatures); 2) Patient temperatures might not be correct; and 3) Temperature-corrected values can be confused with uncorrected values.

He concluded, “Temperature-corrected values should be calculated only when specifically requested and the onus for clinical use of temperature-corrected values lies with the clinician who requests them.”8


Blood gases, electrolytes, metabolites, and CO-Oximetry, as available on whole blood samples, offer added value for today’s clinicians by rapidly providing a bigger picture. Given the critical nature and potential for error of these analytes, the importance of preventing preanalytic errors becomes amplified. Removing air bubbles promptly, proper mixing and remixing, and choosing the correct heparin are all important in reducing error potential. Remove at least twice the dead space for line draws. Be aware of the limitations of temperature-correcting blood gases.

John J. Ancy, MA, RRT, is senior clinical consultant, Instrumentation Laboratory, Bedford, Mass. For further information, contact [email protected].

  1. Department of Health and Human Services. Office of Inspector General. Adverse Events in Hospitals: National Incidence Among Medicare Beneficiaries. November 2010. Available at: Accessed January 10, 2012.
  2. Wilson D. Mistakes chronicled on Medicare patients. The New York Times. Available at: Accessed January 10, 2012.
  3. AARC Pledges to Improve Patient Safety. Available at: Accessed January 10, 2012.
  4. Plebani M, Carraro P. Mistakes in a stat laboratory: types and frequency. Clin Chem. 1997;43(8 Pt 1):1348-51.
  5. CLSI. Blood Gas and pH Analysis and Related Measurements. Approved Guidelines, 2nd ed. Available at: [removed][/removed]. Accessed January 10, 2012.
  6. AARC Clinical Practice Guideline. Blood Gas Analysis and Hemoximetry: 2001 Revision & Update. Available at: Accessed January 10, 2012.
  7. Rickard CM, Couchman BA, Schmidt SJ, Dank A, Purdie DM. A discard volume of twice the deadspace ensures clinically accurate arterial blood gases and electrolytes and prevents unnecessary blood loss. Crit Care Med. 2003;31:1054-8.
  8. Shapiro BA. Temperature correction of blood gas values. Respir Care Clin N Am. 1995;1:69-76.

Resources to Help You Avoid Preanalytic Errors

Radiometer has a fairly extensive offering of tools and information for reducing and avoiding preanalytic errors in blood gas testing. These include:

  • An illustrated, full-color, 20-page handbook called “Avoiding Preanalytical Errors in Blood Gas Testing.” The handbook is free upon request by e-mailing Radiometer through the company’s Web site ( or to .
  • A version of the above handbook focusing on avoiding preanalytic errors in capillary blood gas testing (28 pages). Also available upon request.
  • App versions of the above handbooks, which will be available later in 2012; PDF versions are free and currently downloadable at
  • A PACE- and AARC-accredited Webinar, “Error-Free Preanalytics,” available for playback at: (The recorded version is not AARC accredited, but PACE credits are available through May 2012.)
  • A section devoted to the preanalytic phase of testing on Radiometer’s noncommercial knowledge site, Currently, the site contains more than 50 peer-reviewed articles related to the preanalytic phase.

Instrumentation Laboratory Illumination Webinars
New Perspectives on Reducing Pre-analytical Errors: Arterial Blood Gas Testing (Topic 1 of 3): All Live ILluminations Webinars are recorded and can be viewed up to 18 months after their presentation date. Archived webinars are recorded in multiple languages and formats. Simply select the format and language in which you wish to view from the table and proceed to registration.