Arterial Blood Gas in Hypothermia

OVERVIEW

The solubility of oxygen and carbon dioxide is increased at low temperatures. As a result, there is controversy about how arterial blood gases (ABG) should be interpreted in patients with altered body temperature, with hypothermia being most clinically relevant.

  • Blood gas analyzers warm blood to 37°C
  • Some argue that ABG results need to be corrected for temperature because of this
  • In clinical practice, however, one need only to compare results with normal results at a given temperature — samples warmed to 37C may be compared to normal results at 37C (alpha-stat approach)
  • At any temperature, an uncorrected pH of 7.4 and a PCO2 of 40 mmHg represents normal acid-base balance

The best (simplest) approach in most circumstances is to use uncorrected ABG values compared with the normal values at 37C (alpha-stat approach) (Davis et al, 2013)

UNCORRECTED MEASUREMENTS

A warmed ABG from a hypothermic patient will show a higher PaO2, higher PaCO2, and a lower pH than that actually present in the patient’s blood in vivo

  • The concentration of a solute gas in a solution is directly proportional to the partial pressure of that gas above the solution” according to Henry’s Law (k = P/C, therefore C = P/k). This assumes that temperature remains unchanged.
  • Temperature affects the equilibrium constant for the solvation process (k): the solubility of O2 and CO2 is increased at low temperatures. Thus at low temperatures, there will be a lower partial pressure for a higher dissolved concentration of gas
  • Oxygen and carbon dioxide increase in solubility as water temperature decreases, so their partial pressures will be less

TEMPERATURE CORRECTION OF PO2 and PCO2

Temperature corrections for PaO2 and PaCO2 (Bradley et al, 1956)

  • PaO2 is decreased by 5 mmHg for each degree below 37C
  • PaCO2 is decreased by 2 mmHg for each degree below 37C

TEMPERATURE CORRECTION OF pH

Cooling causes the pH of a blood sample to increase

  • proton dissociation is an endothermic reaction (HA <-> H+ + A-), thus colder temperatures promote equilibration to the left (ie. formation of HA, rather than H+)
  • the change in pH with temperature is almost linear (Ashwood et al, 1983)
  • ‘anaerobic cooling’ of a blood sample (ie cooling in a closed system) causes the pH to increase
  • If required, modern blood gas machines will report the pH value for the actual patient temperature
  • this ‘corrected value’ is calculated mathematically from the pH measured at 37C in the machine

The Rosenthal correction factor is recommended for clinical use

  • Change in pH = 0.015 pH units per degree C change in temperature
  • If the measured pH is 7.360 at a blood gas electrode temperature of 37C, then the pH at a patient temperature of 34°C is calculated as follows: pH = [7.360 + (37-34)(0.015)] = 7.405

ALPHA STAT VERSUS pH STAT

This is a dilemma cardiac anaesthetists, in particular, have grappled with for some time when managing arrested hypothermic cardiac bypass cases (Abdul Aziz and Meduoye, 2010)

  • how should pH and PaCO2 be targeted?
  • what are the implications for the patient?

Two approaches

  • pH-stat approach
    • PaCO2 is maintained at 40 mmHg and the pH is maintained at 7.40 when measured at the patient’s actual temperature (hypothermia)
    • it is, therefore, necessary to add CO2 to the inspired gas (via the oxygenator) to counteract the increased solubility of CO2 at lower temperatures
    • Higher PaCO2 (respiratory acidosis) is targetted than for the alpha-stat approach
  • alpha-stat approach
    • alpha (degree of dissociation) in this approach specifically refers to the ratio of protonated to total imidazole of histidine residues in intracellular proteins
      • 0.55 is considered optimal for the function of intracellular enzymes
      • 0.55 occurs at intracellular pH 6.8 and T 37C, which is seen physiologically
    • paCO2 and the pH are maintained at 40 mmHg and 7.40 when measured at 37 C (i.e. blood sample is warmed to normothermia for measurement)
    • When a patient is cooled during hypothermic cardiac bypass, and measurements are made at the patient’s actual temperature, pH will increase and the measured pCO2 and the pO2 will decrease with lowering of the patient’s temperature
    • Lower PaCO2 is targetted than for the pH-stat approach

Argument for the pH-stat approach targetting higher PaCO2

  • causes cerebral vasodilatation
    • results in increased jugular SvO2 implying increased cerebral blood flow and oxygen delivery
  • causes systemic vasodilatation resulting in faster, more homogeneous cooling
  • counteracts the leftward shift of the haemoglobin-oxygen dissociation curve that occurs with hypothermia and hypothermia-induced alkalaemia
    • increases offloading of haemoglobin to the tissues
    • may increase oxygen delivery
  • may optimise myocardial function

Argument for the alpha-stat approach targetting lower PaCO2

  • maintains pN, the normal pH of neutrality
    • allows cellular transmembrane pH gradients, intracellular trapping of metabolic intermediates, and protein function to be maintained
    • this occurs because protein buffering (via the imidazole rings of histidine residues) is also temperature dependent
  • maintains cerebral autoregulation, which becomes uncoupled with the pH-stat approach
    • avoids potential problems of excess cerebral blood flow such as intracranial hypertension and increased microembolisation
  • the alkaline pH improves cerebral protection during the ischaemic insult
  • avoids errors introduced by inaccurate body temperature measurement

Evidence (Abdul Aziz and Meduoye, 2010)

  • unclear!
  • there is a lack of high-quality research focused on patient-orientated outcomes
  • the alpha-stat approach is more widely accepted

OTHER INFORMATION

Total blood oxygen content actually increases during hypothermia, despite lower PaO2

  • This is due to increased oxygen solubility
  • However, the oxygen content of blood is only slightly increased at 0C versus 37C
  • This is because the primary determinant of oxygen content is oxyhaemoglobin concentration (HbO2), and oxygen binding to haemoglobin is saturable

pH of neutrality (pN) (Brandis, 2015)

  • defined as the state when [H+] = [OH]
  • is temperature dependent
  • occurs at pH 6.8 at 37C
  • intracellular pH has been measured at pH 6.8 at 37C
  • mammalian studies also show that intracellular pH is maintained at approximately pN despite temperature changes
  • experimental work has shown that the imidazole ring of histidine is responsible for the maintenance of pN as it is the only endogenous buffer that has the correct pK and whose pK changes appropriately with temperature

Hypothermia also decreases metabolic rate, resulting in decreased CO2 production and decreased oxygen consumption

  • CaCO2 must be constant across different temperatures to maintain an alpha of 0.55 for the imidazole ring of histidine residues in the blood, which is maintained across compartments experimentally (including intracellularly)
  • this is achieved by changes in CO2 production and minute ventilation at different temperatures

References and Links

Journal articles

  • Abdul Aziz KA, Meduoye A. Is pH-stat or alpha-stat the best technique to follow in patients undergoing deep hypothermic circulatory arrest? Interactive cardiovascular and thoracic surgery. 2010; 10(2):271-82. [pubmed]
  • Ashwood ER, Kost G, Kenny M. Temperature correction of blood-gas and pH measurements. Clinical chemistry. 1983; 29(11):1877-85. [pubmed] [article]
  • Bacher A. Effects of body temperature on blood gases. In: Applied Physiology in Intensive Care Medicine. 2006; Springer, Berlin, Heidelberg [article]
  • Bradley AF, Stupfel M, Severinghaus JW. Effect of Temperature on Pco2 and Po2 of Blood in Vitro. Journal of Applied Physiology. 1956; 9(2):201-204. [pubmed] [article]
  • Burnett RW, Noonan DC. Calculations and correction factors used in determination of blood pH and blood gases. Clinical chemistry. 1974; 20(12):1499-506. [pubmed]
  • Davis MD, Walsh BK, Sittig SE, Restrepo RD. AARC clinical practice guideline: blood gas analysis and hemoximetry: 2013. Respiratory care. 2013; 58(10):1694-703. [pubmed]

FOAM and web resources

CCC 700 6

Critical Care

Compendium

Chris is an Intensivist and ECMO specialist at the Alfred ICU in Melbourne. He is also the Innovation Lead for the Australian Centre for Health Innovation at Alfred Health and Clinical Adjunct Associate Professor at Monash University. He is a co-founder of the Australia and New Zealand Clinician Educator Network (ANZCEN) and is the Lead for the ANZCEN Clinician Educator Incubator programme. He is on the Board of Directors for the Intensive Care Foundation and is a First Part Examiner for the College of Intensive Care Medicine. He is an internationally recognised Clinician Educator with a passion for helping clinicians learn and for improving the clinical performance of individuals and collectives.

After finishing his medical degree at the University of Auckland, he continued post-graduate training in New Zealand as well as Australia’s Northern Territory, Perth and Melbourne. He has completed fellowship training in both intensive care medicine and emergency medicine, as well as post-graduate training in biochemistry, clinical toxicology, clinical epidemiology, and health professional education.

He is actively involved in in using translational simulation to improve patient care and the design of processes and systems at Alfred Health. He coordinates the Alfred ICU’s education and simulation programmes and runs the unit’s education website, INTENSIVE.  He created the ‘Critically Ill Airway’ course and teaches on numerous courses around the world. He is one of the founders of the FOAM movement (Free Open-Access Medical education) and is co-creator of litfl.com, the RAGE podcast, the Resuscitology course, and the SMACC conference.

His one great achievement is being the father of two amazing children.

On Twitter, he is @precordialthump.

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