Monitoring mitochondrial PO2: the next step

PURPOSE OF REVIEW: To fully exploit the concept of hemodynamic coherence in resuscitating critically ill one should preferably take into account information about the state of parenchymal cells. Monitoring of mitochondrial oxygen tension (mitoPO2) has emerged as a clinical means to assess information of oxygen delivery and oxygen utilization at the mitochondrial level. This review will outline the basics of the technique, summarize its development and describe the rationale of measuring oxygen at the mitochondrial level. RECENT FINDINGS: Mitochondrial oxygen tension can be measured by means of the protoporphyrin IX-Triplet State Lifetime Technique (PpIX-TSLT). After validation and use in preclinical animal models, the technique has recently become commercially available in the form of a clinical measuring system. This system has now been used in a number of healthy volunteer studies and is currently being evaluated in studies in perioperative and intensive care patients in several European university hospitals. SUMMARY: PpIX-TSLT is a noninvasive and well tolerated method to assess aspects of mitochondrial functio

Influence of fluid resuscitation on renal microvascular PO(2 )in a normotensive rat model of endotoxemia

INTRODUCTION: Septic renal failure is often seen in the intensive care unit but its pathogenesis is only partly understood. This study, performed in a normotensive rat model of endotoxemia, tests the hypotheses that endotoxemia impairs renal microvascular PO(2 )(μPO(2)) and oxygen consumption (VO(2,ren)), that endotoxemia is associated with a diminished kidney function, that fluid resuscitation can restore μPO(2), VO(2,ren )and kidney function, and that colloids are more effective than crystalloids. METHODS: Male Wistar rats received a one-hour intravenous infusion of lipopolysaccharide, followed by resuscitation with HES130/0.4 (Voluven(®)), HES200/0.5 (HES-STERIL(® )(® )6%) or Ringer's lactate. The renal μPO(2 )in the cortex and medulla and the renal venous PO(2 )were measured by a recently published phosphorescence lifetime technique. RESULTS: Endotoxemia induced a reduction in renal blood flow and anuria, while the renal μPO(2 )and VO(2,ren )remained relatively unchanged. Resuscitation restored renal blood flow, renal oxygen delivery and kidney function to baseline values, and was associated with oxygen redistribution showing different patterns for the different compounds used. HES200/0.5 and Ringer's lactate increased the VO(2,ren), in contrast to HES130/0.4. CONCLUSION: The loss of kidney function during endotoxemia could not be explained by an oxygen deficiency. Renal oxygen redistribution could for the first time be demonstrated during fluid resuscitation. HES130/0.4 had no influence on the VO(2,ren )and restored renal function with the least increase in the amount of renal work

Bilateral Talus and Navicular Fractures accompanied with Unilateral Calcaneal Fracture: A Case Report

An 18-year old male patient, with a history of paragliding accident, sustaining a coronal shear fracture of the body of the talus, an anterior process fracture of the calcaneus extending to the calcaneocuboid joint and a nondisplaced navicular body fracture at the right foot and a displaced fracture of the navicular body accompanied with posteromedial process fracture of the talus at the left side was referred to our emergency clinic. For the right foot, the coronal plane fracture of the talar body was anatomically reduced and fixed with screws. For the left foot, screw fixation was performed through the lateral aspect to fix the large posteromedial fragment. Small bone fragments were removed from the left navicular fracture, and the main fragments were also fixed with screw. The talo-navicular joint was stabilised with a Kirschner wire. At 36 months follow-up, bilateral foot and ankle functions were satisfactory, Maryland scores of the right and left foot were 85 (good) and 90 (excellent), respectively, and the patient regained his full activity level by the 5th month postoperatively. With reference to the number and types of fractures in this one patient, we present a standard protocol for treatment of isolated talus, navicular and calcaneal fractures presenting together in a single foot injury

Measuring Mitochondrial Oxygen Tension during Red Blood Cell Transfusion in Chronic Anemia Patients:A Pilot Study

In light of the associated risks, the question has been raised whether the decision to give a blood transfusion should solely be based on the hemoglobin level. As mitochondria are the final destination of oxygen transport, mitochondrial parameters are suggested to be of added value. The aims of this pilot study were to investigate the effect of a red blood cell transfusion on mitochondrial oxygenation as measured by the COMET device in chronic anemia patients and to explore the clinical usability of the COMET monitor in blood transfusion treatments, especially the feasibility of performing measurements in an outpatient setting. To correct the effect of volume load on mitochondrial oxygenation, a red blood cell transfusion and a saline infusion were given in random order. In total, 21 patients were included, and this resulted in 31 observations. If patients participated twice, the order of infusion was reversed. In both the measurements wherein a blood transfusion was given first and wherein 500 mL of 0.9% saline was given first, the median mitochondrial oxygen tension decreased after red blood cell transfusion. The results of this study have strengthened the need for further research into the effect of blood transfusion tissue oxygenation and the potential role of mitochondrial parameters herein.</p

A simulation of skin mitochondrial PO2 in circulatory shock

Circulatory shock is the inadequacy to supply mitochondria with enough oxygen to sustain aerobic energy metabolism. A novel non-invasive bedside measurement was recently introduced to monitor the mitochondrial oxygen tension in the skin (mitoPO2). As the most downstream marker of oxygen balance in the skin, mitoPO2 may provide additional information to improve shock management. However, a physiological basis for the interpretation of mitoPO2 values has not been established yet. In this paper we developed a mathematical model of skin mitoPO2 using a network of parallel microvessels, based on Krogh's cylinder model. The model contains skin blood flow velocity, heterogeneity of blood flow, hematocrit, arteriolar oxygen saturation and mitochondrial oxygen consumption as major variables. The major results of the model show that normal physiological mitoPO2 is in the range of 40-60mmHg. The relationship of mitoPO2 with skin blood flow velocity follows a hyperbolic curve, reaching a plateau at high skin blood flow velocity, suggesting that oxygen balance remains stable whilst peripheral perfusion declines. The model shows that a critical range exists where mitoPO2 rapidly deteriorates if skin perfusion further decreases. The model intuitively shows how tissue hypoxia could occur in the setting of septic shock, due to the profound impact of microcirculatory disturbance on mitoPO2, even at sustained cardiac output. MitoPO2 is the result of a complex interaction between all factors of oxygen delivery and the microcirculation. This mathematical framework can be used to interpret mitoPO2 values in shock, with the potential to enhance personalized clinical trial design.</p

In Vivo and Ex Vivo Mitochondrial Function in COVID-19 Patients on the Intensive Care Unit

Mitochondrial dysfunction has been linked to disease progression in COVID-19 patients. This observational pilot study aimed to assess mitochondrial function in COVID-19 patients at intensive care unit (ICU) admission (T1), seven days thereafter (T2), and in healthy controls and a general anesthesia group. Measurements consisted of in vivo mitochondrial oxygenation and oxygen consumption, in vitro assessment of mitochondrial respiration in platelet-rich plasma (PRP) and peripheral blood mononuclear cells (PBMCs), and the ex vivo quantity of circulating cell-free mitochondrial DNA (mtDNA). The median mitoVO(2) of COVID-19 patients on T1 and T2 was similar and tended to be lower than the mitoVO(2) in the healthy controls, whilst the mitoVO(2) in the general anesthesia group was significantly lower than that of all other groups. Basal platelet (PLT) respiration did not differ substantially between the measurements. PBMC basal respiration was increased by approximately 80% in the T1 group when contrasted to T2 and the healthy controls. Cell-free mtDNA was eight times higher in the COVID-T1 samples when compared to the healthy controls samples. In the COVID-T2 samples, mtDNA was twofold lower when compared to the COVID-T1 samples. mtDNA levels were increased in COVID-19 patients but were not associated with decreased mitochondrial O(2) consumption in vivo in the skin, and ex vivo in PLT or PBMC. This suggests the presence of increased metabolism and mitochondrial damage

Large emergency-response exercises: qualitative characteristics - a survey

Exercises, drills, or simulations are widely used, by governments, agencies and commercial organizations, to simulate serious incidents and train staff how to respond to them. International cooperation has led to increasingly large-scale exercises, often involving hundreds or even thousands of participants in many locations. The difference between ‘large’ and ‘small’ exercises is more than one of size: (a) Large exercises are more ‘experiential’ and more likely to undermine any model of reality that single organizations may create; (b) they create a ‘play space’ in which organizations and individuals act out their own needs and identifications, and a ritual with strong social implications; (c) group-analytic psychotherapy suggests that the emotions aroused in a large group may be stronger and more difficult to control. Feelings are an unacknowledged major factor in the success or failure of exercises; (d) successful large exercises help improve the nature of trust between individuals and the organizations they represent, changing it from a situational trust to a personal trust; (e) it is more difficult to learn from large exercises or to apply the lessons identified; (f) however, large exercises can help develop organizations and individuals. Exercises (and simulation in general) need to be approached from a broader multidisciplinary direction if their full potential is to be realized