Carboxyhemoglobin half-life toxicokinetic profiles during and after normobaric oxygen therapy: On a swine model.

Investigations on acute carbon monoxide (CO) poisoning struggle to highlight a relevant discriminant criterion related to CO poisoning severity for predicting complications, such as delayed neurological syndromes. In this context, it remains difficult to demonstrate the superiority of one method of oxygen (O2) administration over others or to identify the optimal duration of normobaric 100% oxygen (NBO) treatment. Myoglobin, as hemoglobin, are a potential binding site for CO, which could be a source of extravascular CO storage that impacts the severity of CO poisoning. It is not possible in routine clinical practice to estimate this potential extravascular CO storage. Indirect means of doing so that are available in the first few hours of poisoning could include, for example, the carboxyhemoglobin half-life (COHbt1/2), which seems to be influenced itself by the level and duration of CO exposure affecting this store of CO within the body. However, before the elimination of CO can be assessed, the COHbt1/2 toxicokinetic model must be confirmed: research still debates whether this model mono- or bi-compartmental. The second indirect mean could be the assessment of a potential COHb rebound after COHb has returned to 5% and NBO treatment has stopped. Moreover, a COHb rebound could be considered to justify the duration of NBO treatment. On an experimental swine model exposed to moderate CO poisoning (940 ppm for ±118 min until COHb reached 30%), we first confirm that the COHb half-life follows a bi-compartmental model. Secondly, we observe for the first time a slight COHb rebound when COHb returns to 5% and oxygen therapy is stopped. On the basis of these two toxicokinetic characteristics in favor of extravascular CO storage, we recommend that COHbt1/2 is considered using the bi-compartmental model in future clinical studies that compare treatment effectiveness as a potential severity criterion to homogenize cohorts of the same severity. Moreover, from a general toxicokinetic point of view, we confirm that a treatment lasting less than 6 hours appears to be insufficient for treating moderate CO poisoning.

Effect of Pressure Support Ventilation on Carboxyhemoglobin Toxicokinetic after Acute Carbon Monoxide Intoxication: a Swine Model.

INTRODUCTION: In an experimental study on carbon monoxide (CO) exposure in swine, we aimed to compare the influence of oxygen therapy using a non-rebreathing mask (NRM) to continuous positive airway pressure (CPAP) and two pressure support ventilation (PSV) devices on the decrease of the terminal elimination half-life of carboxyhemoglobin (COHb t1/2). This was the primary outcome. METHODS: Eight spontaneously breathing pigs were sedated by propofol and exposed to 940 ppm CO several times (n = 25) to obtain COHb levels of 30%. CPAPb (high flow open system, CPAP Boussignac® [7.5 cmH2O]), PSV-Vy (open system, Vylife Boussignac®), and PSV-Leg (closed system, Legendair® [inspiratory/expiratory airway pressure 12/4 cmH2O]) devices were used in a randomized order and compared to NRM (O2 at 15 l min-1) and atmospheric air (AA). The primary outcome was COHb t1/2. Multiple comparisons were performed using Dunn's tests. RESULTS: Median FiO2 and minute ventilation were significantly higher in the PSV-Leg group than the NRM group (p < 0.05). Median COHb t1/2 was 251, 85, 82, 93, and 58 min for AA, NRM, CPAPb, PSV-Vy, and PSV-Leg, respectively. All the interventions were superior to AA in terms of CO elimination (p < 0.001), but there was no statistically significant difference between CPAP or PSV and NRM. There was only a trend between PSV-Leg and NRM (p = 0.18). The median AUCs for ln (COHb) × time (h) were 170, 79, 83, 100, and 64 for AA, NRM, CPAPb, PSV-Vy, and PSV-Leg respectively, with a statistically significant difference only between AA and PSV-Leg (p = 0.002). CONCLUSION: In conclusion, in our study on CO intoxication in swine, the use of the closed PSV-Leg system led to the shortest COHb t1/2. These results suggest that PSV-Leg can be more efficient than NRM in eliminating CO and support the design of a clinical study to assess this hypothesis.

Performance of age-adjusted D-dimer cut-off to rule out pulmonary embolism.

BACKGROUND: Age-adjusted D-dimer cut-off has recently been proposed to increase D-dimer usefulness in older patients suspected of pulmonary embolism (PE). OBJECTIVE: We externally validated this age-adjusted D-dimer cut-off using different D-dimer assays in a multicenter sample of emergency department patients. METHODS: Secondary analysis of three prospectively collected databases (two European, one American) of patients suspected of having PE. D-dimer performance for ruling out PE was assessed by calculating negative likelihood ratio (nLR) for D-dimer with age-adjusted D-dimer cut-off (< age × 10 in patients over 50 years) and with conventional cut-off (< 500 µg dL(-1)). Test efficiency was assessed by the number needed to test (NNT) to rule out PE in one patient. RESULTS: Among 4537 patients included, overall PE prevalence was 10.1%. In the overall population, nLR was 0.06 (95% confidence interval, 0.03-0.09) with conventional cut-off and 0.08 (0.05-0.12) with age-adjusted cut-off. Using age-adjusted cut-off, nLR was 0.08, 0.09 and 0.06 for Vidas(®) , Liatest(®) and MDA(®) assays, respectively. Use of age-adjusted cut-off produced a favorable effect on NNT in the elderly; the greatest decrease was observed in patients > 75 years: NTT halved from 8.1 to 3.6. The proportion of patients over 75 years with normal D-dimer was doubled (27.9% vs. 12.3%). CONCLUSIONS: Our study shows that age-adjusted D-dimer had low nLR, allowing its use as a rule-out PE strategy in non-high pretest clinical probability patients, as well as using Vidas(®), Liatest(®) or MDA(®) assays. This age-adjusted cut-off increased clinical usefulness of D-dimer in older patients. A large prospective study is required to confirm these results.