Automated pre-ejection period variation predicts fluid responsiveness in low tidal volume ventilated pigs.

INTRODUCTION: The respiratory variation in the pre-ejection period (Delta PEP) has been used to predict fluid responsiveness in mechanically ventilated patients. Recently, we automated this parameter and indexed it to tidal volume (PEPV) and showed that it was a reliable predictor for post-cardiac surgery, mainly paced, patients ventilated with low tidal volumes. The aims of the present animal study were to investigate PEPV's ability to predict fluid responsiveness under different fluid loading conditions and natural heart rates during low tidal volume ventilation (6 ml/kg) and to compare the performance of PEPV with other markers of fluid responsiveness. METHODS: Eight prone, anesthetized piglets (23-27 kg) ventilated with tidal volumes of 6 ml/kg were subjected to a sequence of 25% hypovolemia, normovolemia, and 25% and 50% hypervolemia. PEPV, Delta PEP, pulse pressure variation (PPV), central venous pressure (CVP), and pulmonary artery occlusion pressure (PAOP) were measured before each volume expansion. RESULTS: Sensitivity was 89% and specificity was 93% for PEPV, 78% and 93% for Delta PEP, 89% and 100% for PPV, 78% and 93% for CVP, and 89% and 87% for PAOP. CONCLUSION: PEPV predicts fluid responsiveness in low tidal volume ventilated piglets.

Should dynamic parameters for prediction of fluid responsiveness be indexed to the tidal volume?

BACKGROUND: The respiratory variation in the pre-ejection period (Delta PEP) has been used to predict fluid responsiveness in mechanically ventilated patients. Recently, we modified this parameter (PEPV) and showed that it was a reliable predictor for post-cardiac surgery, mainly paced, patients when moderately low tidal volumes were used. One of the modifications involved tidal volume indexation, which had not been proposed before for dynamic parameters. The aim of the present animal study was to investigate whether indexation to tidal volume should be part of a new definition of dynamic parameters such as the case for our newly proposed PEPV. METHODS: Eight prone, anesthetized piglets (23-27 kg) were subjected to a sequence of 25% hypovolemia, normovolemia, and 25% and 50% hypervolemia. At each volemic level, tidal volumes were varied in three steps: 6, 9, and 12 ml/kg. PEP variations (ms) and pulse-pressure variation (PPV) were measured during the three tidal volume steps at each volemic level. RESULTS: PEP variations increased significantly with increasing tidal volume at all volemic levels but 50% hypervolemia and were proportionally related to the tidal volume at normovolemia. PPV increased significantly with increasing tidal volume at all volemic levels and was roughly proportional to the tidal volume at all volemic levels but hypovolemia. CONCLUSION: Our study indicates that dynamic parameters are improved by indexing to tidal volume.

Does brain death induce a pro-inflammatory response at the organ level in a porcine model?

BACKGROUND: Organs from brain-dead donors have a poorer prognosis after transplantation than organs from living donors. A possible explanation for this is that brain death might initiate a systemic inflammatory response, elicited by a metabolic stress response or brain ischemia. The aim of this study was to investigate the effect of brain death on the cytokine content in the heart, liver, and kidney. In addition, the metabolic and hemodynamic response caused by brain death was carefully registered. METHODS: Fourteen pigs (35-40 kg) were randomized into two groups (1) eight brain-dead pigs and (2) six pigs only sham operated. Brain death was induced by inflation of an epidurally placed balloon. Blood samples for insulin, glucose, catecholamine, free fatty acids (FAA), and glucagon were obtained during the experimental period of 360 min. At the conclusion of the experiment, biopsies were taken from the heart, liver, and kidney and were analyzed for cytokine mRNA and proteins [tumor necrosis factor alpha (TNF-alpha), interleukin (IL)-6, and IL-10). RESULTS: We found a dramatic response to brain death on plasma levels of epinephrine (P=0.004), norepinephrine (P=0.02), FAA (P=0.0001), and glucagon (P=0.0003) compared with the sham group. There was no difference in cytokine content in any organ between the groups. CONCLUSION: In this porcine model, brain death induced a severe metabolic response in peripheral blood. At the organ level, however, there was no difference in the cytokine response between the groups.

Maximal hysteresis: a new method to set positive end-expiratory pressure in acute lung injury?

BACKGROUND: No methods are superior when setting positive end-expiratory pressure (PEEP) in acute lung injury (ALI). In ALI, the vertical distance (hysteresis) between the inspiratory and expiratory limbs of a static pressure-volume (PV) loop mainly indicates lung recruitment. We hypothesized that PEEP set at the pressure where hysteresis is 90% of its maximum (90%MH) would give similar oxygenation, but less cardiovascular depression than PEEP set at the pressure at lower inflection point (LIP) on the inspiratory limb or at the point of maximal curvature (PMC) on the expiratory limb in ALI. METHODS: In 12 mechanically ventilated pigs, ALI was induced in a randomized fashion by lung lavage, lung lavage plus injurious ventilation, or by oleic acid. From a static PV loop obtained by an interrupted low-flow method, the pressures at LIP [25 (25, 25) cmH(2)O, mean and 25, 75 percentiles], at PMC [24 (20, 24) cmH(2)O], and at 90% MH [19 (18, 19) cmH(2)O] were determined and used for the PEEP-settings. We measured lung inflation (by computed tomography), end-expiratory lung volume (EELV), airway pressures, compliance of the respiratory system (Crs), blood gases, cardiac output and arterial blood pressure. RESULTS: There were no differences between the PEEP settings in EELV or oxygenation, but the 90%MH setting gave lower end-inspiratory pause pressure (P<0.025), higher Crs (P<0.025), less hyper-aeration (P<0.025) and better maintained hemodynamics. CONCLUSION: In this porcine lung injury model, PEEP set at 90% MH gave better lung mechanics and hemodynamics, than PEEP set at PMC or LIP.

Does a positive end-expiratory pressure-induced reduction in stroke volume indicate preload responsiveness? An experimental study.

BACKGROUND: Increases in positive end-expiratory pressure (PEEP) are often associated with cardiovascular depression, responding to fluid loading. Therefore, we hypothesized that if stroke volume (SV) is reduced by an increase in PEEP this reduction is an indicator of hypovolemia or preload responsiveness, i.e. that SV would increase by fluid administration at zero end-expiratory pressure (ZEEP). The relationship between the cardiovascular response to different PEEP levels and fluid load as well as the relation between change in SV as a result of change in preload (Frank-Starling relationship) were evaluated in a porcine model. In addition, other measures of fluid status were assessed. METHODS: Eight, 20-22 kg, anesthetized, mechanically ventilated pigs were subjected to 0, 10, and 20 cm H(2)O PEEP at 10% (of estimated blood volume) hypovolemia, normo- and 10% hypervolemia, and to ZEEP at 20% hypervolemia. SV, cardiac output, intrathoracic blood volume and airway, esophageal, vascular pressures, stroke volume variations, left ventricular end-diastolic and end-systolic areas and respiratory variations in the diameter of the inferior vena cava were obtained. RESULTS: At hypovolemia and normovolemia, 10 cm H(2)O PEEP induced a significant decrease in SV, while no change occurred at 10% hypervolemia. SV measured at ZEEP increased from hypovolemia to normovolemia and 10% hypervolemia, while no change was found between 10% and 20% hypervolemia. The sensitivity and specificity decrease in SV by PEEP indicating an increase in SV by fluids was 60-88% and 67%, respectively, depending on the volemic (preload) levels. CONCLUSION: Although the overall results suggest that a change in SV by PEEP might predict preload responsiveness, the individual response of SV by 10 cm H(2)O PEEP and of the successive fluid administration seemed to be dependent on where on the Frank-Starling curve the heart function was located.

Acute myocardial infarction: does pre-hospital treatment increase survival?

The aim of this study was to assess the impact of a mobile emergency care unit (MECU) staffed with an anaesthetist, in terms of increased survival among patients with acute myocardial infarction (MI). The setting was an urban area with 330 000 inhabitants. This was a quasi-experimental before-and-after-study including consecutive emergency calls during September to November 1996 (Period 1, without the MECU) and September to November 1997 (Period 2, including the MECU). Fifty-four ambulance patients had their MI diagnosis confirmed at hospital during Period 1, and another 54 in Period 2. The 28-day mortality was collected from relevant registers. Twenty-four (44%) of Period 2 patients were transported by the MECU. MECU patients had lower systolic blood pressure (SBP) than other patients, both before and after hospital admission. Nitroglycerine treatment was relatively frequent in MECU patients, and cardioversion, anaesthesia and intubation was applied exclusively in these patients. After arrival at hospital, MECU patients had thrombolysis relatively often (46% versus 23% in other Period 2 patients) but percutaneous transluminal coronary angioplasty (PTCA) relatively infrequently (21% vs 30%). The total mortality was significantly lower in Period 2 than in Period 1 patients (11% vs 21%, <0.025), irrespective of differences in the distribution of age, gender, pulse and SBP, measured at hospital. Also, the more specific MECU use, alone and in combination with subsequent PTCA treatment, was found to be associated with prolonged survival. Pre-hospital treatment by an MECU staffed by an anaesthetist and/or having a PTCA seems to be associated with prolonged survival in acute MI patients. It must be underscored that these observations have been based on quasi-experimental rather than randomized experimental data.