32, 27, 6, 9, 84
Blood flow is the oxygen knob and sweep gas flow is the carbon dioxide knob — but blood flow is ALSO a carbon dioxide knob, with about 1.9 times the effect of gas flow over the ranges studied, which means every intervention that lowers blood flow lowers carbon dioxide clearance too (a weaning trial, a drainage problem, a reduction made for another reason). Sweep gas flow does nothing at all for oxygen transfer, which is the same conclusion Chapter 27 reached from the saturation side. And the negative coefficient on pre-membrane saturation is the arithmetic behind the denominator problem: a measured oxygen transfer falls when the patient improves, in a device that has not changed.
Within-animal comparison across settings, and healthy versus multiple organ failure state
DOI 10.1371/journal.pone.0054954; PMID 23383011; PMC3558498
Systematic variation of blood flow and sweep gas flow
Five animals, one device, one coating; the coefficients are not transferable as numbers to a human circuit and only the rank order and direction of the determinants should be carried across. A higher measured oxygen transfer in the device does not mean more oxygen reaching tissues, as the authors state. Low animal numbers could produce type II errors for the variables that dropped out. THE AUTHORS PRINT ONE COEFFICIENT THEY CANNOT EXPLAIN: higher oxygen transfer at LOWER pre-membrane carbon dioxide runs against the expected direction because a low carbon dioxide raises haemoglobin's oxygen affinity; they say plainly they were unable to bring forth a physiological explanation, offer a speculative one, and concede they cannot exclude residual confounding with blood flow.
OXYGEN TRANSFER (mixed generalised linear model, backward elimination, pseudo-R squared 0.81) had three independent determinants: blood flow (beta plus 0.066 mL/min per mL/min, p under 0.001), pre-membrane oxygen saturation (beta MINUS 1.669 mL/min per percent, p under 0.001 — better blood arriving means LESS measured transfer), and pre-membrane carbon dioxide tension (beta minus 0.964 per mmHg, p equal to 0.001). SWEEP GAS FLOW, TEMPERATURE AND HAEMOGLOBIN ALL DROPPED OUT OF THE OXYGEN MODEL, and stratified by sweep-to-blood ratio the oxygen transmembrane gradient and the oxygen transfer were the same at every ratio tested — no effect of gas flow on oxygenation within the range studied. CARBON DIOXIDE TRANSFER (pseudo-R squared 0.89) had four independent determinants: sweep gas flow (plus 32.910 mL/min per L/min, p under 0.001), blood flow (plus 0.017 per mL/min, p under 0.001), pre-membrane carbon dioxide tension (plus 1.192 per mmHg, p under 0.001) and haemoglobin (minus 3.478 per g/dL, p equal to 0.042); temperature and oxygen saturation dropped out. THE EFFECT OF BLOOD FLOW ON CARBON DIOXIDE TRANSFER WAS ROUGHLY 1.9 TIMES THAT OF GAS FLOW. A 10 mmHg rise in pre-membrane carbon dioxide raised transfer by about as much as an extra 0.5 L/min of sweep, which the authors read as support for permissive hypercapnia. Across the blood flow range oxygen transfer rose about six-fold from 0.5 to 3.0 L/min while carbon dioxide transfer rose about two and a half fold. POST-MEMBRANE VALUES IN A CLEAN DEVICE: oxygen tension 422 (341-463) mmHg at baseline and 354 (188-441) mmHg in multiple organ failure; pH rose 0.09 (0.07-0.13) at baseline and 0.21 (0.13-0.25) in MOF; carbon dioxide fell 10 and 28 mmHg respectively; ionised calcium fell 0.03 mEq/L and chloride rose 2 mEq/L, both statistically significant and clinically trivial; potassium and lactate essentially unchanged.
Five domestic female pigs (80 kg) on venovenous ECMO with a polymethylpentene membrane (PLS Quadrox D, Bioline coating), studied before and after induction of multiple organ failure by saline lung lavage and faecal peritonitis. 45 paired measurements in each condition. Predefined sequence of blood flows (0.5, 1.5, 3.0 L/min) with sweep flows giving gas-to-blood ratios of 1:2, 1:1 and 2:1. Carbon dioxide transfer measured by the reference method, from the gas exhaled by the membrane.