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Table 1 History of carbon monoxide inhalational clinical trials including healthy volunteers and patients. The lower part represents the studies, which have been withdrawn for various reasons. (This list is not exhaustive)

From: Carbon monoxide in intensive care medicine—time to start the therapeutic application?!

Ref.YearFirst authorNumber of participantsCarbon monoxide doseCO-HbOutcome/marker
521973R.D. StewardNot reported100 ppm for 8 h11–13%Feasibility study
531975J.E. Peterson22 volunteers50, 100, and 200 ppm for 5.25 h1–20%Feasibility study, check of Coburn-Forster-Kane equation
551997M. Hausberg10 volunteers30 min of 1000 ppm followed by 30 min of 100 ppm8.3 ± 0.5%Acute sympathetic and hemodynamic effects, no differences between groups
542001Ren11 subjects4000 ppm until CO-Hb = 10%9.7 ± 0.1Respiratory response to prolonged hypoxia, no differences between groups
562001Zevin12 healthy smokers1200–1500 ppm and smoking of at least 20 cigarettes per day for 7 days5 ± 1%No differences in blood pressure or respiratory rate; analysis of platelet factor 4 and urine epinephrine and norepinephrine
582005Mayr9 volunteers500 ppm for 1 h after intravenous LPS injection (2 ng/kg BW)6.5–7.7%TNF, IL-1, IL-6, IL-8 concentrations in plasma showed no differences
622005Resch15 volunteers500 ppm for 1 hour8.5 ± 0.9%Significant increase in retinal and choroidal blood flow
592007Bathoorn20 COPD patients100–125 ppm CO for 2 h on 4 consecutive days4.5%Trend in the reduction of sputum eosinophils, improvement in response to metacholine
572009Rhodes6 subjects100 ppm for 1 h for 5 days3.3 ± 0.6%Significant increase in SOD, HO-1, mitofusin, ATPase-6 and COX-1 proteins due to CO inhalation
602015Pecorella19 subjects200 ppm for 1 h for 5 days5.4 ± 0.8%Significant increase in muscle citrate synthase, mitochondrial density and GLUT4
612016Ryan18 volunteers1.2 mL/kg BW for 30 s for 10 days4.4 ± 0.4%No changes in haemoglobin mass, aerobic performance or peak power exercise tolerance
    Studies withdrawn  
 2007NCT00531856%5.97 mg/L of carbon monoxide in 30% oxygen post transplantation (3 different doses)n.a.Primary outcome: Evaluate the safety and tolerability, secondary: incidence of delayed graft dysfunction (study withdrawn)
 2012NCT01523548%150 ppm for 3 h for 3 weeksn.a.Primary outcome: Evidence of a decrease in pulmonary vascular resistance post-therapy
(Study withdrawn)
 2010NCT01050712%Depending on a healthy control groupn.a.Primary outcome: incidence and duration of postoperative ileus (Study withdrawn)
 2012NCT01727167%200 ppm for 1 hn.a.Primary outcome: Biochemical Markers for Mitochondrial Biogenesis in aortic valve surgery (Study withdrawn)