Ulrich Ehrmann

Ethyl pyruvate improves systemic and hepatosplanchnic hemodynamics and prevents lipid peroxidation in a porcine model of resuscitated hyperdynamic endotoxemia.

Objective:To investigate the systemic, pulmonary, and hepatosplanchnic hemodynamic and metabolic effects of delayed treatment with ethyl pyruvate in a long-term porcine model of hyperdynamic endotoxemia. Design:Prospective, randomized, controlled experimental study with repeated measures. Setting:Investigational animal laboratory. Subjects:Anesthetized, mechanically ventilated, and instrumented pigs. Interventions:After 12 hrs of continuous infusion of lipopolysaccharide and hydroxyethyl starch to keep mean arterial pressure >60 mm Hg, swine randomly received placebo (Ringer’s solution; control group, n = 11) or ethyl pyruvate in lactated Ringer’s solution (n = 8; 0.03 g·kg−1 loading dose over 10 mins, thereafter 0.03 g·kg−1hr−1 for 12 hrs). Measurements and Main Results:Whereas mean arterial pressure significantly decreased in control animals, mean arterial pressure was maintained at the baseline level in pigs treated with ethyl pyruvate. Global oxygen uptake was comparable, so that the trend toward a higher oxygen transport and the significantly higher mixed venous hemoglobin oxygen saturation resulted in a significantly lower oxygen extraction in the ethyl pyruvate group. Ethyl pyruvate reduced intrapulmonary venous admixture and resulted in significantly greater Pao2/Fio2 ratios. Despite comparable urine production in the two groups during the first 18 hrs of endotoxemia, ethyl pyruvate significantly increased diuresis during the last 6 hrs of the study. Lipopolysaccharide-induced systemic and regional venous metabolic acidosis was significantly ameliorated by ethyl pyruvate. Endotoxemia increased both blood nitrate + nitrite and isoprostane concentrations, and ethyl pyruvate attenuated the response of these markers of nitric oxide production and lipid peroxidation. Conclusions:Ethyl pyruvate infusion resulted in improved hemodynamic stability and ameliorated acid-base derangements induced by chronic endotoxemia in pigs. Reduced oxidative stress and an decreased nitric oxide release probably contributed to these effects.

The PARP-1 inhibitor INO-1001 facilitates hemodynamic stabilization without affecting DNA repair in porcine thoracic aortic cross-clamping-induced ischemia/reperfusion

Inhibition of poly (ADP-ribose) polymerase 1 (PARP-1) improved hemodynamics and organ function in various shock models induced by sepsis or ischemia/reperfusion. PARP-1, however, is also referred to play a pivotal role for the maintenance of genomic integrity. Therefore, we investigated the effect of the PARP-1 blocker INO-1001 on hemodynamics, kidney function, and DNA damage and repair during porcine thoracic aortic cross-clamping. The animals underwent 45 min of aortic cross-clamping after receiving vehicle (n = 9) or i.v. INO-1001 (n = 9; total dose, 4 mg·kg−1, administered both before clamping and during reperfusion), data were recorded before clamping, before declamping, and 2 and 4 h after declamping. During reperfusion, continuous i.v. norepinephrine was incrementally adjusted to maintain blood pressure greater than or equal to 80% of the preclamping level. The plasma INO-1001 levels analyzed with high-pressure liquid chromatography were 1 to 1.4 &mgr;mol/L and 0.4 to 0.6 &mgr;mol/L before and after clamping, respectively. Although INO-1001-treated animals required less norepinephrine support, kidney function was comparable in the 2 groups. There was no intergroup difference either in the time course of DNA damage and repair (comet assay) as assessed both in vivo in whole blood before surgery, before clamping, before declamping, 2 h after declamping, and ex vivo in isolated lymphocytes (Ficoll gradient) sampled immediately before clamping and analyzed before, immediately, and 1 and 2 h after exposure to 4 bar 100% O2 for 2 h. There was no difference either in the expression of the cyclin-dependent kinase inhibitor gene, p27, in the kidney (immunohistochemistry). The reduced norepinephrine requirements during reperfusion suggest a positive inotropic effect of INO-1001, as demonstrated by other authors. In our model, INO-1001 proved to be safe with respect to DNA repair.

Efficacy of ventilation and ventilation adjuncts during in-water-resuscitation—A randomized cross-over trial ☆

INTRODUCTION Drowning is a common cause of death in young adults. The 2010 guidelines of the European Resuscitation Council call for in-water-resuscitation (IWR). There has been controversy about IWR amongst emergency and diving physicians for decades. The aim of the present study was assessing the efficacy of IWR. METHODS In this randomized cross-over trial, nineteen lifeguards performed a rescue manoeuvre over a 100 m distance in open water. All subjects performed the procedure four times in random order: with no ventilation (NV) and transportation only, mouth-to-mouth ventilation (MMV), bag-mask-ventilation (BMV) and laryngeal tube ventilation (LTV). Tidal volumes, ventilation rate and minute-volumes were recorded using a modified Laerdal Resusci Anne manikin. Furthermore, water aspiration and number of submersions of the test mannequin were assessed, as well as the physical effort of the lifeguard rescuers.One lifeguard subject did not complete MMV due to exhaustion and was excluded from analysis. RESULTS NV was the fastest rescue manoeuvre (advantage ∼40s). MMV and LTV were evaluated as efficient and relatively easy to perform by the lifeguards. While MMV (mean 199 ml) and BMV (mean 481 ml) were associated with a large amount of aspirated water, aspiration was significantly lower in LTV (mean 118 ml). The efficacy of ventilation was consistently good in LTV (Vt=447 ml), continuously poor in BMV (Vt=197) and declined substantially during MMV (Vt=1,019 ml initially and Vt=786 ml at the end). The physical effort of the lifeguards was remarkably higher when performing IWR: 3.7 in NV, 6.7 in MMV, 6.4 in BMV and 4.8 in LTV as measured on the 0-10 visual analogue scale. CONCLUSION IWR in open water is time consuming and physically demanding. The IWR training of lifeguards should put more emphasis on a reduction of aspiration. The use of ventilation adjuncts like the laryngeal tube might ease IWR, reduce aspiration of water and increase the efficacy of ventilation during IWR.

Effectiveness and Safety of In-Water Resuscitation Performed by Lifeguards and Laypersons: A Crossover Manikin Study

Abstract Objective. Drowning is associated with a high mortality and morbidity and a common cause of death. In-water resuscitation (IWR) in the case of drowning accidents has been recommended by certain resuscitation guidelines in the last several years. IWR has been discussed controversially in the past, especially with regard to the delay of chest compressions, effectiveness of ventilation, and hazard to the rescuer. The aim of the present study was to assess the effectiveness and safety of IWR. Methods. In this crossover manikin study, 21 lifeguards and 21 laypersons performed two rescue procedures in an indoor swimming pool over a 50-meter distance: In random order, one rescue procedure was performed with in-water ventilation and one without. Tidal and minute volumes were recorded using a modified Laerdal Resusci Anne (Laerdal Medical, Stavanger, Norway) and total rescue duration, submersions, water aspiration by the victim, and physical effort were assessed. Results. IWR resulted in significant increases in rescue duration (lifeguards: 106 vs. 82 seconds; laypersons: 133 vs. 106 seconds) and submersions (lifeguards: 3 vs. 1; laypersons: 5 vs. 0). Furthermore, water aspiration (lifeguards: 112 vs. 29 mL; laypersons: 160 vs. 56 mL) and physical effort (lifeguards: visual analog scale [VAS] score 7 vs. 5; laypersons: VAS score 8 vs. 6) increased significantly when IWR was performed. Lifeguards achieved significantly better ventilation characteristics and performed both rescue procedures faster and with lower side effects. IWR performed by laypersons was insufficient with regard to both tidal and minute volumes. Conclusions. In-water resuscitation is associated with a delay of the rescue procedure and a relevant aspiration of water by the victim. IWR appears to be possible when performed over a short distance by well-trained professionals. The training of lifeguards must place particular emphasis on a reduction of submersions and aspiration when IWR is performed. IWR by laypersons is exhausting, time-consuming, and inefficient and should probably not be recommended. Key words: drowning; near-drowning; hypoxia; ventilation, artificial; respiration, artificial; resuscitation, in-water