Effects of resuscitation with human albumin 5%, hydroxyethyl starch 130/0.4 6%, or crystalloid on kidney damage in an ovine model of septic shock.

BACKGROUND: Colloid solutions have been associated with kidney dysfunction in septic animals and humans. The present study investigated the influence of resuscitation with human albumin (HA) 5%, hydroxyethyl starch (HES) 130/0.4 6%, and balanced crystalloids on ultrastructural kidney damage, kidney function, and survival in a model of ovine septic shock. METHODS: After induction of peritoneal septic shock, animals were randomised to one of the following groups: (1) HA 5%, (2) HES 130/0.4 6%, (3) balanced crystalloid, and (4) control (each n=10). Causal therapy included re-laparotomy, peritoneal lavage, and antimicrobial therapy. Sequential kidney biopsies were obtained for the assessment of the electron microscopic tubular injury (EMTI) score. RESULTS: Serum creatinine and urea were highest in the control group, and there were no differences between the intervention groups. Cumulative diuresis was significantly higher in the HA group [1.0 ml kg-1 h-1 (0.6; 1.2)] compared with control [0.7 ml kg-1 h-1 (0.6; 0.9), P<0.05]. Creatinine clearance was highest in the HA and crystalloid groups. Ultrastructural kidney damage was highest in the control group [EMTI score 7.8 (6.7; 9.0)] without differences between intervention groups. Survival was 100% in the colloid groups vs 90% (crystalloid) and 60% (control, all P<0.05). CONCLUSION: In an ovine model of septic shock, kidney function and cumulative diuresis were preserved in the 5% albumin and crystalloid resuscitation groups, whereas HES 130/0.4 6% resulted in diminished creatinine clearance. Differences in kidney function between resuscitation fluids could not be explained by differences in ultrastructural kidney damage. CLINICAL TRIAL REGISTRATION: 84-02.04.2011.A300.

Efficacy and safety of 10% HES 130/0.4 versus 10% HES 200/0.5 for plasma volume expansion in cardiac surgery patients.

AIM: Hydroxyethyl starch (HES) solutions are frequently used for perioperative volume replacement. Whereas older HES specimen tended to accumulate in the plasma and to cause negative effects on hemostasis, more recent products, e.g., HES 130/0.4, are characterised by improved pharmacological properties. The present study was designed to compare the efficacy and safety of 10% HES 130/0.4 and 10% HES 200/0.5. METHODS: In this post-hoc analysis of a prospective, randomised, double-blind, multi-center therapeutic equivalence trial, 76 patients undergoing elective on-pump cardiac surgery received perioperative volume replacement using either 10% HES 130/0.4 (N.=37) or 10% HES 200/0.5 (N.=39) up to a maximum dose of 20 mL kg-1. RESULTS: Equivalent volumes of investigational medication were infused until 24 hours after the first administration (1577 vs. 1540 mL; treatment difference 37 [-150; 223] mL; P<0.0001 for equivalence). Whereas standard laboratory tests of coagulation were comparable between groups, von Willebrand factor activity on the first postoperative morning tended to be higher following treatment with 10% HES 130/0.4 as compared to 10% HES 200/0.5 (P=0.025) with this difference being statistically significant only in the per-protocol analysis (P=0.02). Treatment groups were comparable concerning other safety parameters and the incidence of adverse drug reactions. In particular, renal function was well preserved in both groups. CONCLUSION: Ten percent HES 130/0.4 was equally effective and safe as compared to 10% HES 200/0.5 for volume therapy in patients undergoing cardiovascular surgery. Postoperative coagulation and renal function, as measured by standard laboratory tests, were similar among groups.

Reducing the risk of major elective non-cardiac surgery: is there a role for levosimendan in the preoperative optimization of cardiac function?

Patients with heart failure undergoing non-cardiac surgery still have an unacceptably high morbidity and mortality. Compromised myocardial physiologic reserves in combination with extensive surgery and anesthesia appear to play a crucial role in determining high perioperative morbidity and mortality. Nevertheless, several other mechanisms and pathways such as metabolic factors, ischemia-reperfusion conditions, neurohormonal activation, inflammation and oxidative stress contribute to the adverse outcome. Several cardiovascular drugs have been investigated with the attempt to reduce the incidence of cardiovascular adverse events after major non-cardiac surgery. In the last years, increasing attention has been paid to the use of levosimendan in the perioperative period of patients undergoing cardiac surgery. As an inodilator, levosimendan - at low energy expenditure - may improve perioperative cardiac performance of heart failure patients by optimizing ventriculo-arterial coupling, rather than by increasing myocardial contractility itself. By its vasodilating properties, levosimendan may also improve systemic and regional blood flow. In addition to these hemodynamic properties, non hemodynamic effects of levosimendan may further improve microcirculation and organ function. At the cellular level in the heart, kidney, lung, liver as well as the gut, levosimendan exerts protective preconditioning effects secondary to activation of adenosine triphosphate (ATP)-sensitive potassium channels. Taking into account these multiple but complementary mechanisms, levosimendan appears to be a suitable agent for preoperative optimization of cardiac functions in heart failure patients undergoing major elective surgery. Nevertheless, large-scale trials are needed before final conclusions can be drawn on the use of levosimendan in this indication.

[Sepsis-associated Guillain-Barré syndrome]. / Das Sepsis-assoziierte Guillain-Barré-Syndrom.

This article reports on the case of a multiple trauma patient, who was admitted to the intensive care unit with haemorrhagic shock and severe hypoxaemia. Following posttraumatic septic shock the patient developed quadriplegia 3 weeks after admittance. After having excluded any traumatic and cerebral origins, an analysis of the cerebrospinal fluid was performed and revealed a"dissociation albuminocytologique". This finding in association with limb quadriplegia led to the diagnosis of Guillain-Barré syndrome. Therapy with high-dose i.v. immunoglobulins led to a complete recovery.

Effects of short-term simultaneous infusion of dobutamine and terlipressin in patients with septic shock: the DOBUPRESS study.

BACKGROUND: Terlipressin bolus infusion may reduce cardiac output and global oxygen supply. The present study was designed to determine whether dobutamine may counterbalance the terlipressin-induced depression in mixed-venous oxygen saturation (Svo) in patients with catecholamine-dependent septic shock. METHODS: Prospective, randomized, controlled study performed in a university hospital intensive care unit. Septic shock patients requiring a continuous infusion of norepinephrine (0.9 microg kg(-1) min(-1)) to maintain mean arterial pressure (MAP) at 70 (sd 5) mm Hg were randomly allocated to be treated either with (i) sole norepinephrine infusion (control, n=20), (ii) a single dose of terlipressin 1 mg (n=19), or (iii) a single dose of terlipressin 1 mg followed by dobutamine infusion titrated to reverse the anticipated reduction in Svo2 (n=20). Systemic, pulmonary, and regional haemodynamic variables were obtained at baseline and after 2 and 4 h. Laboratory surrogate markers of organ (dys)function were tested at baseline and after 12 and 24 h. RESULTS: Terlipressin (with and without dobutamine) infusion preserved MAP at 70 (5) mm Hg, while allowing to reduce norepinephrine requirements to 0.17 (0.2) and 0.2 (0.2) microg kg(-1) min(-1), respectively [vs1.4 (0.3) microg kg(-1) min(-1) in controls at 4 h; each P<0.001]. The terlipressin-linked decrease in Svo2 was reversed by dobutamine at a mean dose of 20 (8) microg kg(-1) min(-1) [Svo2 at 4 h: 59 (11)% vs 69 (12)%, P=0.028]. CONCLUSIONS: In human catecholamine-dependent septic shock, terlipressin (with and without concomitant dobutamine infusion) increases MAP and markedly reduces norepinephrine requirements. Although no adverse events were noticed in the present study, potential benefits of increasing Svo2 after terlipressin bolus infusion need to be weighted against the risk of cardiovascular complications resulting from high-dose dobutamine.

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 Levosimendan in intensive care treatment of myocardial insufficiency]. / Rolle von Levosimendan in der intensivmedizinischen Behandlung des myokardialen Pumpversagens.

Levosimendan is a calcium sensitizer that is currently in the focus of intensive care medicine because it may be superior to standard inotropic agents in the treatment of acute myocardial insufficiency. The effects of levosimendan mainly depend on three predominant mechanisms: 1) positive inotropic effect by increasing the sensitivity of cardiac myofilaments to calcium ions, 2) vasodilatory effect by stimulation of adenosine triphosphate-sensitive potassium channels and 3) inhibition of phosphodiesterase-III. In a large number of experimental and clinical studies further possible indications for levosimendan have been described, e.g. cardioprotection during ischemia, cardiogenic shock, septic myocardial insufficiency and pulmonary hypertension. This review article critically summarizes the current scientific and clinical knowledge about levosimendan, its pharmacologic characteristics, mechanisms of action as well as indications and potential risks.

[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.

[Vasopressin and terlipressin in sepsis and systemic inflammatory response syndrome. Effects on microcirculation, oxygen transport, metabolism and organ function]. / Einsatz von Vasopressin und Terlipressin bei Sepsis und systemischen Entzündungsreaktionen. Auswirkungen auf Mikrozirkulation, Sauerstofftransport, Metabolismus und Organfunktion.

Vasopressin and terlipressin are increasingly used as alternative non-adrenergic vasopressors for hemodynamic support of septic patients with arterial hypotension. Despite excellent vasopressive effects, vasopressin analogues may potentially impair macro-hemodynamics, oxygen transport and microvascular blood flow. Due to those unwanted side-effects, vasopressin and terlipressin may potentially compromise organ function and possibly foster the development of multiple organ failure. This review article discusses the results of clinical and experimental studies to judge the effects of vasopressin and terlipressin on microcirculation, oxygen supply, metabolism and organ function in patients with sepsis or systemic inflammatory response syndrome (SIRS). Although vasopressin analogues are emerging as promising alternatives to treat catecholamine-refractory hypotension, there is no evidence that vasopressin receptor agonists improve outcome. To date, vasopressin and terlipressin can, therefore, not be recommended for routine clinical use.