Tommaso Fiore

Does perioperative hemodynamic optimization protect renal function in surgical patients? A meta-analytic study

Objective:Postoperative acute deterioration in renal function, producing oliguria and/or increase in serum creatinine, is one of the most serious complication in surgical patients. Most cases are due to renal hypoperfusion as a consequence of systemic hypotension, hypovolemia, and cardiac dysfunction. Although some evidence suggests that perioperative monitoring and manipulation of oxygen delivery by volume expansion and inotropic drugs may decrease mortality in surgical patients, no study analyzed this approach on postoperative renal dysfunction. The objective of this investigation is to perform a meta-analysis on the effects of perioperative hemodynamic optimization on postoperative renal dysfunction. Data Sources, Study Selection, Data Extraction:A systematic literature review, using MEDLINE, EMBASE, and The Cochrane Library databases through January 2008 was conducted and 20 studies met the inclusion criteria (4220 participants). Data synthesis was obtained by using odds ratio (OR) with 95% confidence interval (CI) by random-effects model. Data Synthesis:Postoperative acute renal injury was significantly reduced by perioperative hemodynamic optimization when compared with control group (OR 0.64; CI 0.50-0.83; p = 0.0007). Perioperative optimization was effective in reducing renal injury defined consistently with risk, injury, failure, and loss and end-stage kidney disease and Acute Kidney Injury Network classifications, and in studies defining renal dysfunction by serum creatinine and/or need of renal replacement therapy only (OR 0.66; CI 0.50-0.88; p = 0.004). The occurrence of renal dysfunction was reduced when treatment started both preoperatively and intraoperatively or postoperatively, was performed in high-risk patients, and was obtained by fluids and inotropes. Mortality was significantly reduced in treatment group (OR 0.50; CI 0.31-0.80; p = 0.004), but statistical heterogeneity was observed. Conclusions:Surgical patients receiving perioperative hemodynamic optimization are at decreased risk of renal impairment. Because of the impact of postoperative renal complications on adverse outcome, efforts should be aimed to identify patients and surgery that would most benefit from perioperative optimization.

Cardiorespiratory Effects of Positive End-expiratory Pressure during Progressive Tidal Volume Reduction (Permissive Hypercapnia) in Patients with Acute Respiratory Distress Syndrome

Background In patients with acute respiratory distress syndrome (ARDS), the ventilatory approach is based on tidal volume (VT) of 10-15 ml/kg and positive end-expiratory pressure (PEEP). To avoid further pulmonary injury, decreasing VT and allowing PaCO2 to increase (permissive hypercapnia) has been suggested. Effects of 10 cmH sub 2 O of PEEP on respiratory mechanics, hemodynamics, and gas exchange were compared during mechanical ventilation with conventional (10-15 ml/kg) and low (5-8 ml/kg) VT.

Melatonin protects against heart ischemia-reperfusion injury by inhibiting mitochondrial permeability transition pore opening

Melatonin, a well-known antioxidant, has been shown to protect against ischemia-reperfusion myocardial damage. Mitochondrial permeability transition pore (MPTP) opening is an important event in cardiomyocyte cell death occurring during ischemia-reperfusion and therefore a possible target for cardioprotection. In the present study, we tested the hypothesis that melatonin could protect heart against ischemia-reperfusion injury by inhibiting MPTP opening. Isolated perfused rat hearts were subjected to global ischemia and reperfusion in the presence or absence of melatonin in a Langerdoff apparatus. Melatonin treatment significantly improves the functional recovery of Langerdoff hearts on reperfusion, reduces the infarct size, and decreases necrotic damage as shown by the reduced release of lactate dehydrogenase. Mitochondria isolated from melatonin-treated hearts are less sensitive than mitochondria from reperfused hearts to MPTP opening as demonstrated by their higher resistance to Ca(2+). Similar results were obtained following treatment of ischemic-reperfused rat heart with cyclosporine A, a known inhibitor of MPTP opening. In addition, melatonin prevents mitochondrial NAD(+) release and mitochondrial cytochrome c release and, as previously shown, cardiolipin oxidation associated with ischemia-reperfusion. Together, these results demonstrate that melatonin protects heart from reperfusion injury by inhibiting MPTP opening, probably via prevention of cardiolipin peroxidation.

A comparison between fenoldopam and low-dose dopamine in early renal dysfunction of critically ill patients*

Objective:Fenoldopam mesylate is a selective dopamine-1 agonist, with no effect on dopamine-2 and &agr;1 receptors, producing a selective renal vasodilation. This may favor the kidney oxygen supply/demand ratio and prevent acute renal failure. The aim of the study was to investigate if fenoldopam can provide greater benefit than low-dose dopamine in early renal dysfunction of critically ill patients. Design:Prospective, multiple-center, randomized, controlled trial. Setting:University and city hospital intensive care units. Patients:One hundred adult critically ill patients with early renal dysfunction (intensive care unit stay <1 wk, hemodynamic stability, and urine output ≤0.5 mL/kg over a 6-hr period and/or serum creatinine concentration ≥1.5 mg/dL and ≤ 3.5 mg/dL). Interventions:Patients were randomized to receive 2 &mgr;g/kg/min dopamine (group D) or 0.1 &mgr;g/kg/min fenoldopam mesylate (group F). Drugs were administered as continuous infusion over a 4-day period. Measurements and Main Results:Systemic hemodynamic and renal function variables were recorded daily. The two groups were well matched at enrollment for illness severity and hemodynamic and renal dysfunction. No differences in heart rate or systolic, diastolic, or mean arterial pressure were observed between groups. Fenoldopam produced a more significant reduction in creatinine values compared with dopamine after 2, 3, and 4 days of infusion (change from baseline at time 2, −0.32 vs. −0.03 mg/dL, p = .047; at time 3, −0.45 vs. −0.09 mg/dL, p = .047; and at time 4, −.041 vs. −0.09 mg/dL, p = .02, in groups F and D, respectively). The maximum decrease in creatinine compared with baseline was significantly greater in group F than group D (−0.53 ± 0.47 vs. −0.34 ± 0.38 mg/dL, p = .027). Moreover, 66% of patients in group F had a creatinine decrease >10% of the baseline value at the end of infusion, compared with only 46% in dopamine group (chi-square = 4.06, p = .04). Total urinary output during drug infusion was not significantly different between groups. After 1 day, urinary output was lower in group F compared with group D (p < .05). Conclusions:In critically ill patients, a continuous infusion of fenoldopam at 0.1 &mgr;g/kg/min does not cause any clinically significant hemodynamic impairment and improves renal function compared with renal dose dopamine. In the setting of acute early renal dysfunction, before severe renal failure has occurred, the attempt to reverse renal hypoperfusion with fenoldopam is more effective than with low-dose dopamine.

Inhomogeneity of lung parenchyma during the open lung strategy: a computed tomography scan study.

RATIONALE The open lung strategy aims at reopening (recruitment) of nonaerated lung areas in patients with acute respiratory distress syndrome, avoiding tidal alveolar hyperinflation in the limited area of normally aerated tissue (baby lung). OBJECTIVES We tested the hypothesis that recruited lung areas do not resume elastic properties of adjacent baby lung. METHODS Twenty-five anesthetized, mechanically ventilated pigs were studied. Four lung-healthy pigs served as controls and the remaining 21 were divided into three groups (n = 7 each) in which lung injury was produced by surfactant lavage, lipopolysaccharide infusion, or hydrochloride inhalation. Computed tomography scans, respiratory mechanics, and gas exchange parameters were recorded under three conditions: at baseline, during lung recruitment maneuver, and at end-expiration and end-inspiration when ventilating after an open lung protocol. MEASUREMENTS AND MAIN RESULTS During recruitment maneuver and open lung protocol, the gas volume entering the insufficiently aerated compartment was 96% (75-117%) and 48% (41-63%) (median [interquartile range]) of the functional residual capacity measured before and at zero end-expiratory pressure, respectively. Nonetheless, the volume of hyperinflated lung increased during both recruitment maneuver (by 1-28% of total lung volume; P < 0.01) and open lung protocol ventilation at end-inspiration (by 1-15% of total lung volume; P < 0.01). Regional elastance of recruited lung tissue was consistently higher than that of the baby lung regardless of the ARDS model (P < 0.01). CONCLUSIONS Alveolar recruitment is not protective against hyperinflation of the baby lung because lung parenchyma is inhomogeneous during ventilation with the open lung strategy.

Effects of Proportional Assist Ventilation on Inspiratory Muscle Effort in Patients with Chronic Obstructive Pulmonary Disease and Acute Respiratory Failure

Background Acute respiratory failure may develop in patients with chronic obstructive pulmonary disease because of intrinsic positive end‐expiratory pressure (PEEPi) and increased resistive and elastic loads. Proportional assist ventilation is an experimental mode of partial ventilatory support in which the ventilator generates flow to unload the resistive burden (flow assistance: FA) and volume to unload the elastic burden (volume assistance: VA) proportionally to inspiratory muscle effort, and PEEPi can be counterbalanced by application of external PEEP. The authors assessed effects of proportional assist ventilation and optimal ventilatory settings in patients with chronic obstructive pulmonary disease and acute respiratory failure. Methods Inspiratory muscles and diaphragmatic efforts were evaluated by measurements of esophageal, gastric, and transdiaphragmatic pressures. Minute ventilation and breathing patterns were evaluated by measuring airway pressure and flow. Measurements were performed during spontaneous breathing, continuous positive airway pressure, FA, FA + PEEP, VA, VA + PEEP, FA + VA, and FA + VA + PEEP. Results FA + PEEP provided the greatest improvement in minute ventilation (89 +/‐ 3%) and dyspnea (62 +/‐ 2%). The largest reduction in pressure time product per breath of the respiratory muscles and diaphragm (44 +/‐ 3% and 33 +/‐ 2%, respectively) also was observed during FA + PEEP condition. When VA was added to this setting, a reduction in respiratory rate (50 +/‐ 3%), an increase in inspiratory time (102 +/‐ 6%), and a further reduction in pressure time product per minute (65 +/‐ 2% and 64% for the respiratory muscles and diaphragm, respectively) was observed. However, values of pressure time product per liter of minute ventilation during FA + VA + PEEP did not differ with those observed during FA + PEEP condition. Worsening of patient‐ventilator interaction and breathing asynchrony occurred when VA was implemented. Conclusions Application of PEEP to counterbalance PEEPi and FA to unload the resistive burden provided the optimal conditions in such patients. Ventilator over‐assistance and patient‐ventilator asynchrony was observed when VA was added to this setting. The clinical use of proportional assist ventilation should be based on continuous measurements of respiratory mechanics.

Use of N-terminal pro-brain natriuretic peptide to detect acute cardiac dysfunction during weaning failure in difficult-to-wean patients with chronic obstructive pulmonary disease.

Objective: To evaluate the utility of serial measurements of plasma N‐terminal pro‐brain natriuretic peptide (NT‐proBNP) to detect acute cardiac dysfunction during weaning failure in difficult to wean patients with chronic obstructive pulmonary disease. Design: Prospective observational cohort study. Setting: A 14‐bed general intensive care unit in a university hospital. Patients: Nineteen patients mechanically ventilated for chronic obstructive pulmonary disease exacerbation who were difficult to wean. Interventions: None. Measurements and Main Results: Cardiac and hemodynamic variables, arterial and central venous blood gas, breathing pattern, respiratory mechanics, indexes of oxygen cost of breathing, and plasma levels of NT‐proBNP were measured and analyzed immediately before (baseline) and at the end of a spontaneous breathing trial. Eight of 19 patients (42%) were identified with acute cardiac dysfunction at the end of the weaning trial. Baseline NT‐proBNP levels were significantly higher (median 5000, interquartile range 4218 pg/mL) in these patients than in patients without evidence of acute cardiac dysfunction (median 1705, interquartile range 3491 pg/mL). Plasma levels of NT‐proBNP increased significantly at the end of the spontaneous breathing trial only in patients with acute cardiac dysfunction (median 12,733, interquartile range 16,456 pg/mL, p < .05). The elevation in NT‐proBNP at the end of the weaning trial had a good diagnostic performance in detecting acute cardiac dysfunction, as estimated by area under the receiver operating characteristic curve analysis (area under the curve 0.909, se 0.077, 95% confidence interval 0.69–0.98; p < .0001, cutoff = 184.7 pg/mL). Conclusions: Serial measurements of NT‐proBNP plasma levels provided a noninvasive manner to detect acute cardiac dysfunction during an unsuccessful weaning trial in difficult to wean patients with chronic obstructive pulmonary disease. The utility of this test as a complement of the standard clinical monitoring of the weaning trial deserves further investigation.

Patient-requested neuraxial analgesia for labor: impact on rates of cesarean and instrumental vaginal delivery.

A systematic review, including a meta-analysis, on the timing effects of neuraxial analgesia (NA) on cesarean and instrumental vaginal deliveries in nulliparous women was conducted. Of 20 articles identified, 9 met the inclusion quality criteria (3,320 participants). Cesarean delivery (odds ratio, 1.00; 95% confidence interval, 0.82–1.23) and instrumental vaginal delivery (odds ratio, 1.00; 95% confidence interval, 0.83–1.21) rates were similar in the early NA and control groups. Neonates of women with early NA had a higher umbilical artery pH and received less naloxone. In the early NA group, fewer women were not compliant with assigned treatment and crossed over to the control group. Women receiving early NA for pain relief are not at increased risk of operative delivery, whereas those receiving early parenteral opioid and late epidural analgesia present a higher risk of instrumental vaginal delivery for nonreassuring fetal status, worse indices of neonatal wellness, and a lower quality of maternal analgesia.

Pulmonary atelectasis during low stretch ventilation: "open lung" versus "lung rest" strategy

Objective:Limiting tidal volume (VT) may minimize ventilator-induced lung injury (VILI). However, atelectasis induced by low VT ventilation may cause ultrastructural evidence of cell disruption. Apoptosis seems to be involved as protective mechanisms from VILI through the involvement of mitogen-activated protein kinases (MAPKs). We examined the hypothesis that atelectasis may influence the response to protective ventilation through MAPKs. Design:Prospective randomized study. Setting:University animal laboratory. Subjects:Adult male 129/Sv mice. Interventions:Isolated, nonperfused lungs were randomized to VILI: VT of 20 mL/kg and positive end-expiratory pressure (PEEP) zero; low stretch/lung rest: VT of 6 mL/kg and 8–10 cm H2O of PEEP; low stretch/open lung: VT of 6 mL/kg, two recruitment maneuvers and 14–16 cm H2O of PEEP. Ventilator settings were adjusted using the stress index. Measurement and Main Result:Both low stretch strategies equally blunted the VILI-induced derangement of respiratory mechanics (static volume-pressure curve), lung histology (hematoxylin and eosin), and inflammatory mediators (interleukin-6, macrophage inflammatory protein-2 [enzyme-linked immunosorbent assay], and inhibitor of nuclear factor-kB[Western blot]). VILI caused nuclear swelling and membrane disruption of pulmonary cells (electron microscopy). Few pulmonary cells with chromatin condensation and fragmentation were seen during both low stretch strategies. However, although cell thickness during low stretch/open lung was uniform, low stretch/lung rest demonstrated thickening of epithelial cells and plasma membrane bleb formation. Compared with the low stretch/open lung, low stretch/lung rest caused a significant decrease in apoptotic cells (terminal deoxynucleotidyl transferase mediated deoxyuridine-triphosphatase nick end-labeling) and tissue expression of caspase-3 (Western blot). Both low stretch strategies attenuated the activation of MAPKs. Such reduction was larger during low stretch/open lung than during low stretch/lung rest (p < 0.001). Conclusion:Low stretch strategies provide similar attenuation of VILI. However, low stretch/lung rest strategy is associated to less apoptosis and more ultrastructural evidence of cell damage possibly through MAPKs-mediated pathway.

AUTO–POSITIVE END-EXPIRATORY PRESSURE AND DYNAMIC HYPERINFLATION

PEEP is indicated in patients with COPD only to unload the respiratory muscles from the auto-PEEP resulting from expiratory flow limitation. If auto-PEEP is not caused by flow limitation, application of PEEP will cause further hyperinflation, worsening respiratory mechanics, muscle activity, and hemodynamics. To assess the presence of expiratory flow limitation correctly, to measure auto-PEEP correctly, and to identify the maximal PEEP level to be used, measurements of flow and opening pressure must be obtained during a brief period of suspended respiratory muscle activity (obtained by sedation) with the patients own breathing pattern reproduced accurately.