Exogenous adrenomedullin prevents and reverses hypodynamic circulation and pulmonary hypertension in ovine endotoxaemia.

BACKGROUND: Hypodynamic septic shock is associated with a poor prognosis. The present randomized-controlled laboratory experiment was designed to test the hypothesis that the vasodilatory peptide hormone adrenomedullin (ADM) is a useful agent to prevent and reverse the development of hypodynamic circulation in ovine endotoxaemia. METHODS: Twenty-four healthy ewes were chronically instrumented for haemodynamic monitoring and randomly allocated to either the control, treatment, or prophylaxis group (n = 8 each). After a baseline (BL) measurement in the healthy state, all sheep were subjected to a continuous endotoxin infusion started at 10 ng kg(-1) min(-1) and doubled every hour six times. After 4 h of endotoxin challenge, the treatment group received ADM (50 ng kg(-1) min(-1)) for the remaining 3 h of the experiment. The prophylaxis group received a simultaneous infusion of endotoxin and ADM (50 ng kg(-1) min(-1)) from the beginning to the end of the 7 h intervention period. RESULTS: In the control and treatment groups, the ewes exhibited a hypodynamic circulation at 4 h (>20% reduction in cardiac index, both P < 0.01 vs BL). Endotoxin also increased mean pulmonary arterial pressure (MPAP) and arterial lactate concentrations. Prophylactic infusion of ADM prevented the occurrence of pulmonary hypertension and hypodynamic circulation and thereby blunted the increase in arterial lactate concentrations. In the treatment group, ADM administration increased CI (P < 0.001) and reduced both MPAP (P = 0.023) and arterial lactate concentrations (P < 0.001 each at 7 h) when compared with the control group. CONCLUSIONS: This study demonstrates that exogenous ADM prevents and reverses hypodynamic circulation, attenuates pulmonary hypertension, and limits lactic acidosis in ovine endotoxaemia.

Processing of stored packed red blood cells using autotransfusion devices decreases potassium and microaggregates: a prospective, randomized, single-blinded in vitro study.

The aim of the study was to compare the potential of autotransfusion devices to reduce non-infectious complications related to transfusion of long-stored packed red blood cells (PRBC; n= 57), such as changes in electrolytes, blood cells and the load of free microaggregates. Following a baseline measurement, a blood pool of three PRBC was divided into three equal volumes and washed with either the Haemonetics Cell Saver (HCS) or the continuous autotransfusion system (C.A.T.S), using the quality (CATS(quality)) and emergency (CATS(emergency)) mode. After the washing procedure, measurements for electrolytes, blood cells and free microaggregates were repeated (n= 19 each). Compared with baseline, the investigated autotransfusion devices reduced the median load of potassium (baseline: 52 mEq L(-1); HCS: 4 mEq L(-1); CATS(quality): 4 mEq L(-1); CATS(emergency): 17 mEq L(-1); each P < 0.001), restored a physiologic electrolyte balance and significantly decreased the load of leucocytes, glucose and protein. Whereas the quantity of microaggregates was not reduced by HCS, CATS(emergency) decreased the load of cell fragments below 7.8 microm (P < 0.05 vs. baseline). Using CATS(quality) decreased the load of cell fragments not only to a diameter below 7.8 microm (P < 0.001 vs. baseline) but also of microaggregates between 7.8 and 17.6 microm (P < 0.05 vs. baseline). In situations where long-stored PRBC have to be transfused, the procedure described here may be feasible to reduce clinically relevant side effects, i.e. hyperkalaemia and microvascular obstruction secondary to free cell fragments. This approach could be especially useful in patients undergoing massive transfusion and/or suffering from renal failure.

[Role of adrenomedullin in the pathogenesis and treatment of cardiovascular dysfunctions and sepsis]. / Bedeutung von Adrenomedullin Pathogenese und Behandlung kardiovaskulärer Dysfunktionen der Sepsis.

Adrenomedullin (AM) is an endogenous vasodilatory peptide hormone, which plays a key role in the regulation and preservation of cardiovascular and pulmonary functions. Clinical and experimental studies have demonstrated that AM represents an alternative therapeutic option in the treatment of pulmonary hypertension. In addition, AM proved to be useful in the treatment of cardiovascular dysfunctions, such as arterial hypertension and congestive heart failure following myocardial infarction. Recent research has also shown that AM plays a pivotal role in the development of sepsis-associated hemodynamic and microcirculatory disorders. Experimental studies also suggest that infusion of exogenous AM might be a rational approach to prevent and treat hypodynamic septic shock. The objectives of this review article are to characterize the regulative properties of AM and to discuss clinical and experimental studies which allow to judge the role of AM in the setting of cardiovascular dysfunction and sepsis.

New approach to an ovine model of hypodynamic endotoxaemia.

BACKGROUND AND OBJECTIVE: Since the moribund hypodynamic phase of septic shock has primarily been studied in small animal models, the objective of this study was to investigate the usefulness of infusing Salmonella typhosa endotoxin at incrementing doses to establish an ovine model of hypodynamic endotoxaemia. METHODS: In a prospective laboratory experiment, eight adult ewes were instrumented for a chronic study. Following a baseline measurement in the healthy state, a continuous endotoxin infusion was started with 10 ng kg(-1) min(-1) and was doubled every hour seven times. Haemodynamics, key variables of oxygen transport, and arterial lactate concentrations were determined every hour. RESULTS: In a dose-dependent manner, endotoxin infusion caused pulmonary hypertension, decreased cardiac output and mean arterial pressure, increased heart rate, and to a certain extent, systemic vascular resistance index. Following 4h of endotoxaemia, the maximum decrease in cardiac output occurred (4.8+/-0.2 vs. 7.6+/-0.3 Lmin(-1); P < 0.001). This was accompanied by tissue dysoxia, represented by decreases in oxygen delivery (797+/-20 vs. 1041+/-28 mLmin(-1)), oxygen consumption (277+/-14 vs. 396+/-15 mLmin(-1)) and oxygen extraction rate (0.35+/-0.01 vs. 0.38+/-0.01%; each P < 0.01), as well as an increase in arterial lactate concentration (1.7+/-0.1 vs. 0.7+/-0.1 mmolL(-1); P < 0.05). CONCLUSIONS: This large animal model may be helpful to study the pathophysiology responsible for cardiovascular failure, and also new therapeutic approaches relevant to management of hypodynamic circulation in the common setting of progressed systemic inflammation.

Strategies to reduce perioperative blood loss related to non-surgical bleeding.

The treatment of critically ill patients has advanced markedly over the last decade. However, non-surgical bleeding of a diffuse nature from numerous tiny capillaries still remains a challenge. Once initiated, this type of bleeding may be troublesome and a vicious circle develops since it is not a single vessel contributing to this blood loss. The description 'non-surgical blood loss' is often given to this. This review describes a step-by-step approach for the treatment of non-surgical bleeding and includes various measures, such as desmopressin, blood components, antifibrinolytics, antithrombin III, prothrombin complex concentrates and factor XIII. While most non-surgical bleedings can be managed using the approach described here, a number of patients still continue to bleed. In these cases, the surgeon should re-evaluate the bleeding in terms of its surgical origin. If this can positively be excluded and if all of measures described fail to reduce or stop the bleeding, further treatment of such uncontrolled bleeding remains symptomatic.

Anaesthetic strategies to reduce perioperative blood loss in paediatric surgery.

In adults, a number of measures to reduce perioperative blood loss have been established. These techniques serve to reduce patients' exposure to homologous blood. Most adults are concerned with this issue especially since many patients became infected with human immunodeficiency virus (HIV) during the 1980s through exposure to blood components. While blood-saving strategies are widely used in adults, they are mostly neglected in infants. However, it is these young patients with their whole life in front of them who, it could be argued, would benefit especially from any potentially avoidable infection (HIV, hepatitis, etc.) or immunological complications. In infants and small children, these blood-sparing techniques may not be as effective as in adults and technical limitations may prevent their application. However, some of these measures can be used and may serve to prevent or reduce exposure to homologous blood. In the following review, blood-saving techniques established in adults are described and their applicability for paediatric patients discussed.

Intraoperative washing of long-stored packed red blood cells by using an autotransfusion device prevents hyperkalemia.

IMPLICATIONS: Long-stored packed red blood cells (PRBCs) have a large potassium load. In patients with end-stage renal failure, the transfusion of such PRBCs may cause a critical increase in plasma potassium levels. Washing PRBCs with an autotransfusion device allows for a marked decrease in potassium load, thus preventing hyperkalemia.

Thoracic, but not lumbar, epidural anesthesia improves cardiopulmonary function in ovine pulmonary embolism.

UNLABELLED: We hypothesized that sympathetic stimulation is the main mechanism contributing to hemodynamic failure in pulmonary embolism. We investigated the effects of epidural anesthesia-induced sympathetic blockade, restricted to thoracic and lumbar levels, during pulmonary embolism. Two experiments were performed in chronically instrumented ewes. In the first experiment, six sheep received 6 mL bupivacaine 0.175% (Thoracic Epidural Anesthesia [TEA] group), and six sheep received 6 mL saline 0.9% (TEA-Control group), respectively, via an epidural catheter (T3 level). In the second experiment, six sheep received 2.8 mL bupivacaine 0.375% (Lumbar Epidural Anesthesia [LEA] group), and six sheep received 2.8 mL saline 0.9% (LEA-Control group) epidurally (L4 level). Embolization was performed by IV injection of autologous blood clots (Experiment 1, 0.75 mL/kg; Experiment 2, 0.625 mL/kg). TEA was associated with significantly slower heart rates, decreased mean pulmonary artery pressures and central venous pressures, and significantly higher stroke volume index and oxygenation in comparison with the TEA-Control group. By contrast, LEA was associated with significantly faster heart rates and increased central venous pressures and with a significantly lower stroke volume index in comparison with the LEA-Control group. TEA significantly reduced, and LEA significantly increased, hemodynamic deterioration, suggesting beneficial effects of TEA on cardiopulmonary function during pulmonary thromboembolism. IMPLICATIONS: Thoracic (but not lumbar) epidural anesthesia was associated with beneficial cardiopulmonary effects during experimental pulmonary thromboembolism in sheep.

Fat elimination from autologous blood.

Bowl-based autotransfusion devices reduce the amount of fat found in shed blood, but cannot completely eliminate fat particles. When fat is seen on the surface of the processed blood, this blood should be filtered with a leukocyte removal filter before retransfusion.

Anaesthesia and the elderly.

As a result of age-related physiological changes and multi-comorbidity, which both result in reduced functional reserve of the organ systems, old patients are more vulnerable to surgical stress and perioperative impairment in organ functions. Therefore, the incidence of severe complications during the perioperative course is increased in the elderly. Regional anaesthesia or a combination of regional and general anaesthesia is considered to be beneficial in elderly patients, because neuraxial blockade may reduce sympathetic activation, and has been demonstrated to reduce postoperative mortality. Other protective strategies to maintain organ functions in elderly patients include medication with beta-blockers in patients with cardiovascular risks, the avoidance of hypothermia, the maintenance of systemic oxygen delivery, and patient-controlled pain therapy.

[Massive transfusion with the Rapid Infusion System. Its effect on core body temperature]. / Massivtransfusion mit dem Rapid Infusion System. Einfluss auf die Körperkerntemperatur.

Extensive blood loss requires adequate volume replacement. However the infused volume cannot be adequately warmed especially when high infusion rates are necessary. Subsequently, hypothermia develops and results in hemodynamic instability and coagulopathy. The Rapid Infusion System (RIS) allows high infusion rates (up to 1.5 l/min) while at the same time guaranteeing sufficient warming. The efficacy of the RIS was investigated in 43 consecutive patients who required a massive transfusion. The average volume transfused in these patients was 31.7 +/- 4.5 l (minimum: 7.8 l; maximum: 165.3 l) which is equal to an average exchange of 6.4 times the circulating blood volume (maximum: 39.4 blood volumes). The replacement of such high blood volumes has not yet been published in a series of patients. Despite these high transfusion rates, the body core temperature was maintained at 35.85 +/- 0.1 degrees C. Only five patients had a body core temperature below 34 degrees C, all were trauma patients and four of these five patients already had a preoperative temperature below 34 degrees C. The mortality in this study was 28%, which is markedly reduced in comparison to previous publications although they all considered at patients with significantly less blood loss. Maintaining normothermia and normovolemia by the use of the RIS may explain the improved outcome.