Patrick Lauscher

Norepinephrine increases tolerance to acute anemia.

Objective:Extreme anemia threatens myocardial oxygen supply by 1) a decline of arterial oxygen content and 2) by a decline of mean aortic pressure (MAP) and thus coronary perfusion pressure. Standard treatment of low arterial oxygen content includes ventilation with pure oxygen and the transfusion of red blood cells. However, it is unknown whether the stabilization of MAP and coronary perfusion pressure with norepinephrine as the sole therapeutic modality may also increase tolerance to extreme anemia and thus improve outcome. Design:Prospective, randomized, controlled study. Setting:Experimental animal laboratory of a university hospital. Subjects:A total of 28 anesthetized, mechanically ventilated pigs. Interventions and Measurements:In the first protocol, 14 anesthetized pigs were hemodiluted by exchange of whole blood for 6% hydroxyethyl starch (200,000:0.5) until the individual critical hemoglobin concentration was reached. For the next 6 hrs, animals were either observed without any further intervention (control group) or their MAP was maintained by adapted infusion of norepinephrine (norepinephrine group). The main outcome variable of this protocol was the 6-hr mortality in both groups. In the second protocol, 14 anesthetized pigs received hemodilution until death. In seven animals, no intervention was performed during the hemodilution procedure, whereas in the other seven animals, MAP was maintained at >60 mm Hg by adapted infusion of norepinephrine. The main outcome variable of this protocol was the maximum exchangeable blood volume until death. Main Results:MAP stabilization with norepinephrine reduced the 6-hr mortality at the critical hemoglobin concentration from 100% to 14%. Maintaining MAP by adapted norepinephrine infusion during the hemodilution procedure allowed for the exchange of 125 (110/126) (median [quartile 1/quartile 3]) mL/kg blood (163% of blood volume) in the norepinephrine group, whereas only 76 (73/91) mL/kg blood (104% of blood volume) could be exchanged in the control group. Conclusions:Application of norepinephrine can be judged a first-line intervention to bridge acute anemia via a stabilization of MAP and coronary perfusion pressure. However, due to the relevant side effects of norepinephrine, its sole long-term use during extreme anemia without concomitant transfusion of erythrocytes is not advised.

Determination of organ-specific anemia tolerance.

Objective:Utilization of anemia tolerance reduces the need for and risks of perioperative transfusion. Recent publications indicate that the critical limit for oxygen supply might not be the same for each organ system. Therefore, we investigated the effects of acute dilutional anemia on heart, brain, kidneys, liver, small intestine, and skeletal muscle to quantify organ-specific tolerance of different levels of acute anemic hypoxia. We hypothesized that, in some organs, tissue hypoxia occurs before the critical limits of systemic oxygen supply are reached. Design:Laboratory animal experiments. Setting:Animal research laboratory at university medical school. Subjects:A total of 18 domestic pigs of either sex (average weight: 19.6 kg). Interventions:Animals were anesthetized, ventilated, and randomized into three groups and then hemodiluted by exchange of 6% hydroxyethyl starch (130,000:0.4) for whole blood to the group-specific endpoint: Sham (no hemodilution), Hb4 (hemoglobin 4.3 g/dL), Hbcrit (2.7 g/dL). Subsequently, 10 mg/kg pimonidazole (which forms protein adducts in hypoxic cells) was injected. One hour after injection, tissue samples were collected and analyzed for pimonidazole-protein adduct quantification (dot blot) and as a surrogate for transcriptional activation during hypoxia the expression of vascular endothelial growth factor messenger RNA. Relevant hemodynamic and metabolic parameters were collected. Measurements and Main Results:Hemodynamics, metabolic parameters, or oxygen consumption did not indicate that tissue oxygenation was restricted before reaching Hbcrit. However, kidneys and skeletal muscle showed enhanced pimonidazole binding and vascular endothelial growth factor expression at Hb4. By contrast, liver oxygenation was actually improved at Hb4. Heart, brain, and liver showed no signs of tissue hypoxia at Hb4. Conclusions:Heart, brain, kidneys, liver, small intestine, and skeletal muscle experience tissue hypoxia at different degrees of acute anemia, as assessed by the pimonidazole method and vascular endothelial growth factor expression. Further studies are needed to elucidate the mechanisms that determine organ-specific anemia tolerance.

Hyperoxia Reversibly Alters Oxygen Consumption and Metabolism

Aim. Ventilation with pure oxygen (hyperoxic ventilation: HV) is thought to decrease whole body oxygen consumption (VO2). However, the validity and impact of this phenomenon remain ambiguous; until now, under hyperoxic conditions, VO2 has only been determined by the reverse Fick principle, a method with inherent methodological problems. The goal of this study was to determine changes of VO2, carbon dioxide production (VCO2), and the respiratory quotient (RQ) during normoxic and hyperoxic ventilation, using a metabolic monitor. Methods. After providing signed informed consent and institutional acceptance, 14 healthy volunteers were asked to sequentially breathe room air, pure oxygen, and room air again. VO2, VCO2, RQ, and energy expenditure (EE) were determined by indirect calorimetry using a modified metabolic monitor during HV. Results. HV reduced VO2 from 3.4 (3.0/4.0) mL/kg/min to 2.8 (2.5/3.6) mL/kg/min (P < 0.05), whereas VCO2 remained constant (3.0 [2.6/3.6] mL/kg/min versus 3.0 [2.6/3.5] mL/kg/min, n.s.). After onset of HV, RQ increased from 0.9 (0.8/0.9) to 1.1 (1.0/1.1). Most changes during HV were immediately reversed during subsequent normoxic ventilation. Conclusion. HV not only reduces VO2, but also increases the respiratory quotient. This might be interpreted as an indicator of the substantial metabolic changes induced by HV. However, the impact of this phenomenon requires further study.

Low hemoglobin levels during normovolemia are associated with electrocardiographic changes in pigs.

We studied whether low hemoglobin concentrations during normovolemia change the myocardial electrical current (electrocardiogram) in a pig model. Normovolemic anemia was achieved by stepwise replacing blood with colloids (hydroxyethyl starch 6%). We measured the length of the PQ-, QT-, QTc, and the ST interval as well as the amplitude of the Q wave and T wave at hemoglobin concentrations of 9.5, 8.0, 5.5, 3.8, and 3.3 g·dL−1. Normovolemic anemia is accompanied by a gradual prolongation of the QT and QTc interval and a reduction in the amplitude of the T wave. The QRS complex is partly diminished in amplitude. Results were verified performing a time-frequency analysis on single heartbeats. During severe anemia and normovolemia, electrocardiographic changes can be detected. Further investigations are warranted to elucidate whether these changes indicate myocardial hypoxia.

Perioperative Red Blood Cell Transfusion: Harmful or Beneficial to the Patient?

Although the transfusion of red blood cells (RBCs) is safer than ever regarding infections, it is still associated with several adverse reactions and therefore should only be used on the basis of evidence-based triggers. However prevention of RBC transfusion and subsequent substitution of blood losses with acellular solutions will inevitably result in dilutional anemia. Acute dilutional anemia can be compensated by the body over a wide range of hemoglobin concentrations without a critical restriction of tissue oxygenation. On the other hand, chronic anemia is known to be a potent cause of morbidity and mortality. As a consequence, the impact of perioperative anemia on mortality is difficult to describe, because anemia, as well as the transfusion of RBCs, can influence the clinical outcome. The resulting ‘Gordian knot’ cannot be cut easily, and this circumstance forces clinical physicians to make a daily trade-off between transfusion-associated and anemia-associated risks. This review focuses on the physiology of oxygen transport, the hazards of acute anemia, the hazards of RBC transfusion, and the literature putting these problems into perspective.

Hyperoxic ventilation improves survival in pigs during endotoxaemia at the critical hemoglobin concentration

AIM OF THE STUDY Recently it has been demonstrated that short term hyperoxic ventilation (HV) can improve glucose metabolism, reduce pulmonary and hepatic apoptosis, and improve gastrointestinal perfusion during acute sepsis. However, it is unknown whether additional O(2) improves survival. Therefore we investigated the effects of increased plasma O(2) on survival during extreme anaemia and concomitant endotoxaemia in order to quantify the efficacy of HV. METHODS Endotoxaemia (Salmonella abortus equi-LPS) was induced in 14 anesthetized pigs ventilated with room air (FiO(2)=0.21). Simultaneously, animals were haemodiluted by exchange of whole blood for 6% hydroxyethyl starch (200,000:0.5) until the individual critical hemoglobin concentration (Hb(crit)) was achieved (outermost limit of tissue oxygenation). Subsequently, animals were either ventilated with an FiO(2) of 0.21 (NOX, n=7) or an FiO(2) of 1.0 (HOX, n=7), and observed thereafter for 6 h without further intervention. RESULTS HV significantly prolonged survival time at Hb(crit) (NOX, 30 [27/35] min; HOX, 172 [111/235] min, p<0.05). In contrast to the NOX group, HV maintained MAP, and improved DO(2) and tissue oxygenation in the HOX group. CONCLUSION The improvement of survival, oxygen transport and tissue oxygenation seems to underline the efficacy of HV during endotoxaemia and concomitant acute anaemia. Further studies are needed to transfer these results into daily clinical practice.

Effects of alterations of inspiratory oxygen fractions on heart rate variability

BACKGROUND Changes in heart rate variability (HRV) during anaesthesia depend on multiple influences such as hypnosis, analgesia, surgical stress, and interacting drugs. Several recent studies have aimed to establish HRV-based monitoring tools to measure perioperative stress or anaesthetic depth. Although hyperoxic ventilation (HV) is known to alter autonomic cardiovascular regulation, there have been no studies investigating its influence on time- and frequency-domain analysis during general anaesthesia. Therefore, we have examined the effects of HV on cardiovascular neuroregulation of anaesthetized patients and conscious volunteers by analysis of relevant HRV parameters. METHODS Fourteen healthy volunteers and 14 anaesthetized, ventilated ASA I patients sequentially breathed room air ( 0.21), pure oxygen ( 1.0), and then room air. During each episode, standardized HRV parameters were calculated from 5 min ECG recordings. RESULTS HV significantly reduced HR and increased the standard deviation of RR interval values, the root mean square of successive RR interval differences, and the high-frequency (HF) power of the spectral components, whereas the low-frequency (LF) power and the LF/HF ratio of HRV were reduced in both groups. All changes were reversible after was reduced to normoxia. CONCLUSIONS In both healthy volunteers and anaesthetized patients, HV resulted in comparable and reversible changes of established HRV parameters. These changes might be relevant enough to bias HRV-based analgesia and anaesthesia monitoring and could result in a clinically relevant misinterpretation of HRV parameters as indicators of anaesthetic depth during HV.

Rationaler Einsatz von Blutprodukten : Die wichtigsten Regeln für den transfundierenden Arzt

During the last decades drug safety of blood- and plasma products have been raised significantly. Moreover, since 2008 the usage of blood- and plasma products was determined in a clinical practice guideline for blood- and plasma products by the Bundesärztekammer. This document underlays a current update and exists in its actual 4. revision. Aim oft the manuscript presented is to summarize the content of these clinical practice guidelines concerning the most important points like indications for transfusion (physiological and hb-bound transfusion triggers), the right choice of red blood cell concentrate, and the most common side effects.

Effects of hyperoxic ventilation on 6-h survival at the critical haemoglobin concentration aggravated by experimentally induced tachycardia in anaesthetized pigs.

Aim:  Administration of 100% oxygen [hyperoxic ventilation (HV)] has been proven to ameliorate oxygen transport, tissue oxygenation and survival in different models of extreme normovolemic and hypovolemic anaemia. However, up to date, it is unknown whether HV is also able to improve outcome of extreme anaemia if myocardial oxygen consumption is contemporaneously increased by tachycardia. Therefore, we investigated the influence of HV on the 6‐h survival rate during extreme anaemia and aggravated by experimentally induced tachycardia in a prospective, randomized study in a pig model of critical anaemia.

Anemia tolerance during normo-, hypo-, and hypervolemia.

Restrictive intraoperative fluid management has been demonstrated to improve outcome of visceral and lung surgery in several studies. However, subsequent hypovolemia (HOV) may be accompanied by a decrease of anemia tolerance, resulting in increased transfusion needs. We therefore investigated the effect of volume status on anemia tolerance.