ABSTRACT
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.
Subject(s)
Acute Kidney Injury/etiology , Crystalloid Solutions/toxicity , Hydroxyethyl Starch Derivatives/toxicity , Serum Albumin, Human/toxicity , Shock, Septic/therapy , Acute Kidney Injury/physiopathology , Animals , Creatinine/blood , Crystalloid Solutions/therapeutic use , Disease Models, Animal , Drug Administration Schedule , Female , Fluid Therapy/adverse effects , Fluid Therapy/methods , Hemodynamics/physiology , Hydroxyethyl Starch Derivatives/therapeutic use , Norepinephrine/administration & dosage , Oxygen Consumption/physiology , Random Allocation , Serum Albumin, Human/therapeutic use , Sheep, Domestic , Shock, Septic/physiopathology , Vasoconstrictor Agents/administration & dosageABSTRACT
The present review initially describes the rationale for the use of non-adrenergic vasopressors in the treatment of distributive shock and then provides an overview of the individual vasopressin-receptor agonists, namely arginine vasopressin, terlipressin, and selepressin. Following a brief summary of their current use in clinical practice, the present review focuses on the influence of vasopressin-receptor agonists on macro- and microvascular coupling, also referred to as hemodynamic coherence. On the basis of the current evidence from experimental and clinical studies, vasopressin-receptor agonists do not negatively influence macro- and microvascular coupling as compared to the standard therapy with norepinephrine, when used in established treatment regimes. A higher selectivity for the V1a-receptor seems to be beneficial; however, future clinical trials are warranted to verify this assumption. Notably, the optimal treatment regime for non-adrenergic vasopressors with respect to compound, dose, and timing still needs to be defined.
Subject(s)
Microcirculation/drug effects , Shock, Septic , Vasoconstrictor Agents/pharmacology , Adrenergic Agents/pharmacology , Hemodynamics/drug effects , Humans , Receptors, Vasopressin/agonists , Shock, Septic/drug therapy , Shock, Septic/physiopathology , Vasoconstrictor Agents/therapeutic useABSTRACT
Arginine vasopressin (AVP) and its synthetic, long-acting analog terlipressin (TP) are potent alternative vasoconstrictors in the treatment of septic patients with catecholamine-refractive vasodilatatory shock. The results from one large randomized clinical trial suggest that AVP plus norepinephrine (NE) infusion is as safe and effective as treatment with NE alone in patients with septic shock. Because the desired effects of vasopressin analogs are basically related to their vasopressinergic effects via the V1a receptor, more selective V1 agonists, such as TP, may be more potent in reversing sepsis-related arterial hypotension. In this regard, recent evidence from small-scale studies suggests that continuous low-dose infusion rather than intermittent bolus injection of TP is associated with fewer side effects, such as depression of cardiac output and rebound arterial hypotension. However, because clinical data on the administration of TP in patients with sepsis are limited, it should not currently be used beyond the scope of controlled trials. The optimal time point for the initiation of therapy with vasopressin analogs has yet to be determined. While AVP and TP are commonly used as last-resort therapies in severe septic shock, some evidence supports the initiation of treatment in a less severe state of the disease.
