Biomedical subjects

Suzana M Lobo

Publications and source records attributed to Suzana M Lobo.

7 recordsLinked to original sources

PubMed2026

Safety and outcomes of dapagliflozin initiation in critically ill patients with acute kidney injury: A post-hoc analysis of the defender trial.

BACKGROUND: SGLT2 inhibitor use in acute kidney injury (AKI) is controversial due to concerns about hemodynamic instability. We evaluated dapagliflozin initiation in critically ill patients with AKI enrolled in the DEFENDER trial. METHODS: Among 212 patients with AKI at enrollment (100 dapagliflozin, 112 control), we compared 28-day mortality, kidney replacement therapy (KRT), and composite death/KRT. Adjusted risk differences were estimated controlling for age, sepsis, baseline vasopressor use, and creatinine. Physiological trajectories (creatinine, urine output, fluid balance, acid-base parameters) over days 1-5 were analyzed using mixed models. Likelihood ratios quantified compatibility with clinically meaningful harm or benefit. RESULTS: Event rates were similar: 28-day mortality 38% vs 40%, KRT 12% vs 18%, composite 41% vs 42% (dapagliflozin vs control). Adjusted risk differences were - 1.9% (95% CI -14.5 to 10.7) for death, -7.4% (-16.2 to 1.5) for KRT, and - 0.9% (-13.6 to 11.8) for the composite. Physiological trajectories showed no divergence suggestive of hemodynamic or metabolic instability. Likelihood ratios provided limited separation: at 5% absolute effect threshold, LR against harm was 1.47 and against benefit 1.19. CONCLUSIONS: Dapagliflozin initiation in critically ill patients with AKI was not associated with excess mortality, KRT, or physiological derangement. The near-neutral evidential profile indicates neither moderate harm nor benefit can be excluded, supporting feasibility of dedicated trials of SGLT2 inhibitors in AKI.

Humans↗

PubMed2006

Prospective, randomized trial comparing fluids and dobutamine optimization of oxygen delivery in high-risk surgical patients [ISRCTN42445141].

INTRODUCTION: Preventing perioperative tissue oxygen debt contributes to a better postoperative recovery. Whether the beneficial effects of fluids and inotropes during optimization of the oxygen delivery index (DO2I) in high-risk patients submitted to major surgeries are due to fluids, to inotropes, or to the combination of the two is not known. We aimed to investigate the effect of DO2I optimization with fluids or with fluids and dobutamine on the 60-day hospital mortality and incidence of complications. METHODS: A randomized and controlled trial was performed in 50 high-risk patients (elderly with coexistent pathologies) undergoing major elective surgery. Therapy consisted of pulmonary artery catheter-guided hemodynamic optimization during the operation and 24 hours postoperatively using either fluids alone (n = 25) or fluids and dobutamine (n = 25), aiming to achieve supranormal values (DO2I > 600 ml/minute/m2). RESULTS: The cardiovascular depression was an important component in the perioperative period in this group of patients. Cardiovascular complications in the postoperative period occurred significantly more frequently in the volume group (13/25, 52%) than in the dobutamine group (4/25, 16%) (relative risk, 3.25; 95% confidence interval, 1.22-8.60; P < 0.05). The 60-day mortality rates were 28% in the volume group and 8% in the dobutamine group (relative risk, 3.00; 95% confidence interval, 0.67-13.46; not significant). CONCLUSION: In patients with high risk of perioperative death, pulmonary artery catheter-guided hemodynamic optimization using dobutamine determines better outcomes, whereas fluids alone increase the incidence of postoperative complications.

Aged↗

PubMed2006

Initial and delayed onset of acute respiratory failure: factors associated with development and outcome.

In a prospective observational study of 1038 adult admissions to a 31-bed medical/surgical intensive care unit (ICU), acute respiratory failure (ARF, defined as a Pao(2)/Fio(2) ratio 48 h after ICU admission) in 49 (16%). On admission, the cardiovascular sequential organ failure assessment (SOFA) score was higher in initial than in delayed onset ARF (1.1 +/- 1.5 vs 0.6 +/- 1.2, P < 0.05). High admission serum C-reactive protein concentrations (OR 1.08, 95% CI 1.04-1.12, P = 0.0001) and SOFA scores (OR 1.20, 95% CI 1.08-1.33, P = 0.0007) were the factors independently associated with initial ARF, and a low Glasgow coma scale (GCS) score (OR 1.13, 95% CI 1.04-1.21, P = 0.0018) was associated with delayed onset ARF. In initial ARF, a high SOFA score (OR 1.24, 95% CI 1.12-1.38, P = 0.0001) and a low GCS score (OR 0.89, 95% CI 0.83-0.96, P = 0.0013) on admission, and in delayed onset ARF, a low GCS score at 48 h (OR 0.67, 95% CI 0.54-0.84, P = 0.0011) were independently associated with death. The mortality rate was similar for initial and delayed onset ARF.

Adult↗

PubMed2005

Pneumonia-induced sepsis and gut injury: effects of a poly-(ADP-ribose) polymerase inhibitor.

BACKGROUND: Pseudomonas aeruginosa is commonly associated with nosocomial pneumonia. Ileal mucosal injury may be induced by severe lung infection. During septic shock, peroxynitrite-mediated DNA strand-breaks activate the enzyme poly-(ADP)-ribose polymerase (PARP) resulting in cellular energetic suppression and cell dysfunction. The aim of this study was to determine whether gut injury could be demonstrated in sepsis induced by P. aeruginosa and the effects of a PARP inhibitor (PJ34) on the associated gut injury. MATERIALS AND METHODS: After baseline measurements, 20 rabbits were randomized into three groups: Sham (n = 5): transtracheally inoculated (TI) with 2 ml of phosphate buffer solution (PBS); P. aeruginosa + saline (n = 8), TI with 4 x 10(12) CFU/ml of P. aeruginosa in 2 ml/kg of PBS + i.v. saline; and P. aeruginosa + PJ34 (n = 7), TI with 4 x 10(12) CFU/ml of P. aeruginosa and i.v. treatment with PJ34. RESULTS: P. aeruginosa caused a hyperdynamic response with increased blood flow also in the superior mesenteric artery. No significant differences were found in luminal gut lactate concentrations or PCO(2)-gap between groups. Histological specimens showed moderate or diffuse alveolar infiltrate in the P. aeruginosa + saline group (6/8) and in the P. aeruginosa + PJ34 group (6/7). Gut wet-to-dry weight ratio was significantly higher in the P. aeruginosa + saline group than in Shams (7.5 +/- 0.8 versus 6.4 +/- 0.7, P < 0.05) and significantly lower in the P. aeruginosa + PJ34 group (6.1 + 0.5, P < 0.05 versus the other groups). Blood cultures were positive in 1/5 (Sham), 8/8 (P. aeruginosa + saline group) and 4/7 (P. aeruginosa + PJ34 group) (RR 0.57 CI 95% 0.30-1.08). CONCLUSIONS: Pharmacological inhibition of PARP reduces gut inflammation and may limit bacterial translocation.

Animals↗

PubMed2005

[Comparison of dobutamine under different fluids resuscitation for shock induced by ischemia/reperfusion].

OBJECTIVE: To compare the effects of dobutamine under different fluids resuscitation for shock induced by intestinal ischemia/reperfusion (I/R) injury in rabbits. METHODS: Thirty-two anesthetized rabbits were randomized into four groups of eight animals each. The groups were followed as: (1) lactated Ringer's solution (LRS) resuscitation; (2) LRS+hydroxyethyl starch solution (HES) resuscitation; (3) LRS resuscitation+dobutamine treatment; (4) LRS+HES resuscitation+dobutamine treatment. All these rabbits underwent the intestinal I/R injury developed by occluding superior mesenteric artery (SMA) with a non-crushing vascular clamp for 60 minutes and then loosing the clamp for 300 minutes. The fluid resuscitation and drug treatment began at the same time of reperfusion. Hemodynamic parameters including mean artery pressure (MAP), heart rate (HR), aortic velocity (AoV, as cardiac output) and SMA blood flow (Qsma) were measured. Tissue oxygenation was assessed indirectly by measuring the tonometric parameters of the gut, including difference between partial pressure of carbon dioxide in intestinal intramucosal and partial pressure of carbon dioxide in arterial blood (Pt-a CO2 gap), intestinal intramucosal pH (pHi), arterial blood lactate acid concentration and oxygen delivery (DO2). RESULTS: HR, AoV and Qsma as measured in two dobutamine groups were significantly higher in values than LRS and LRS+HES groups (all P<0.05). But MAP as measured in two dobutamine groups were significantly higher in values than only LRS (P<0.05), and in LRS+HES resuscitation+dobutamine treatment group was also significantly higher in values than LRS resuscitation+dobutamine treatment group (P<0.05). Dobutamine in LRS resuscitation+dobutamine treatment and LRS+HES resuscitation+dobutamine treatment group could greatly decrease lactate and Pt-aCO2 gap, significantly improve pHi and DO2 compared with other two resuscitation groups (all P<0.05). Dobutamine in LRS+HES resuscitation+dobutamine treatment group could also greatly decrease lactate and Pt-aCO2 gap, significantly improve pHi compared with LRS resuscitation+dobutamine treatment group (all P<0.05). CONCLUSION: Dobutamine could improve hemodynamic parameters and tissue oxygenation in shock induced by intestinal I/R injury in rabbits, being better used under the LRS+HES resuscitation.

Animals↗

PubMed2004

[Roles of hydroxyethyl starch solution in resuscitation for shock induced by ischemia/reperfusion injury of the intestine].

OBJECTIVE: To compare the effects of high and low doses of 6% hydroxyethyl starch solution (HES) on resuscitation for shock induced by ischemia/reperfusion injury of the intestine in rabbits. METHODS: Thirty-two anesthetized rabbits were randomized into four groups of eight animals each. The animals in the control group received no fluid resuscitation, animals in group 2 received lactated Ringer's solution (LRS, 20 ml x kg(-1) x h(-1)), those in group 3 received LRS+HES (LRS 18 ml x kg(-1) x h(1)+HES 2 ml x kg(-1) x h(-1), low dosage of HES), and those in group 4 received HES only in high dosage of HES (20 ml x kg(-1) x h(-1)). All these rabbits underwent intestinal ischemia/reperfusion injury developed by occluding superior mesenteric artery (SMA) with a non-crushing vascular clamp for 60 minutes and then the clamp was loosened for 240 minutes. The fluid resuscitation began at the same time of reperfusion. Hemodynamic parameters including mean artery pressure, heart rate, aortic velocity (as cardiac output), and SMA blood flow were measured. Tissue oxygenation was assessed indirectly by measuring the tonometric parameters of the gut, including difference between partial pressure of carbon dioxide in intestinal intramucosal and partial pressure of carbon dioxide in arterial blood (Pt-aCO(2) gap), intestinal intramucosal pH (pHi), arterial blood lactate acid concentration and oxygen delivery. Mortality of the rabbits was counted at the end of the experiment. RESULTS: Hemodynamic parameters as measured in low and high doses of HES groups were significantly higher in values than LRS group (LRS) and control (all P<0.05). Low dose of HES was better in restoring hemodynamic parameters than high dose of HES (all P<0.05). Low dose of HES could greatly decrease lactate and Pt-aCO(2) gap, significantly improve pHi compared with other three groups (all P<0.05), but high dose of HES did not do so, and oral and nasal bleeding even death of some animals were seen. Low dose and high dose of HES significantly improved oxygen delivery while LRS did not (all P<0.05). CONCLUSION: Low dose of HES together with LRS is more effective than only high dose of HES or LRS in the resuscitation for shock induced by ischemia/reperfusion injury of the intestine in rabbits, resulting in better hemodynamic parameters and tissue oxygenation.

Animals↗

PubMed2003

Gut mucosal damage during endotoxic shock is due to mechanisms other than gut ischemia.

Whether the gut alterations seen during sepsis are caused by microcirculatory hypoxia or disturbances in cellular metabolic pathways associated with mitochondrial respiration remains controversial. We hypothesized that hypoperfusion or hypoxia and local production of nitric oxide might play an important role in the development of gut mucosal injury during endotoxic shock and investigated their roles by using differing levels of fluid resuscitation and occlusion of the superior mesenteric artery (SMA). Anesthetized New Zealand rabbits were allocated to group I (sham, n = 8); group II [low-dose endotoxin (LPS, Escherichia coli-055:B5, 150 microg/kg)/fluid resuscitation (12 ml x kg(-1) x h(-1)); n = 8]; group III [high-dose LPS (1 mg/kg)/fluid resuscitation (12 ml x kg(-1) x h(-1)); n = 8]; group IV [high-dose LPS (1 mg/kg)/hypovolemia (4 ml x kg-1 x h(-1) fluids); n = 8]; and group V [SMA ligation/fluid resuscitation (12 ml x kg(-1) x h(-1)); n = 4]. Luminal gut lactate concentrations and PCO2 gap increased in groups IV and V (P < 0.05), reflecting alterations in gut perfusion. Interestingly, significant histological alterations were observed in all LPS groups but not in group V. Blood and luminal gut nitrate/nitrite concentrations increased only in group IV. The mechanism of gut injury in endotoxic shock seems unrelated to hypoxia and release of nitric oxide. Gut dysfunction may occur as a result of so-called "cytopathic hypoxia."

Animals↗