Increasing arterial blood pressure with norepinephrine does not improve microcirculatory blood flow: a prospective study

Introduction

Our goal was to assess the effects of titration of a norepinephrine infusion to increasing levels of mean arterial pressure (MAP) on sublingual microcirculation.

Methods

Twenty septic shock patients were prospectively studied in two teaching intensive care units. The patients were mechanically ventilated and required norepinephrine to maintain a mean arterial pressure (MAP) of 65 mmHg. We measured systemic hemodynamics, oxygen transport and consumption (DO₂ and VO₂), lactate, albumin-corrected anion gap, and gastric intramucosal-arterial PCO₂ difference (ΔPCO₂). Sublingual microcirculation was evaluated by sidestream darkfield (SDF) imaging. After basal measurements at a MAP of 65 mmHg, norepinephrine was titrated to reach a MAP of 75 mmHg, and then to 85 mmHg. Data were analyzed using repeated measurements ANOVA and Dunnett test. Linear trends between the different variables and increasing levels of MAP were calculated.

Results

Increasing doses of norepinephrine reached the target values of MAP. The cardiac index, pulmonary pressures, systemic vascular resistance, and left and right ventricular stroke work indexes increased as norepinephrine infusion was augmented. Heart rate, DO₂ and VO₂, lactate, albumin-corrected anion gap, and ΔPCO₂ remained unchanged. There were no changes in sublingual capillary microvascular flow index (2.1 ± 0.7, 2.2 ± 0.7, 2.0 ± 0.8) and the percent of perfused capillaries (72 ± 26, 71 ± 27, 67 ± 32%) for MAP values of 65, 75, and 85 mmHg, respectively. There was, however, a trend to decreased capillary perfused density (18 ± 10,17 ± 10,14 ± 2 vessels/mm², respectively, ANOVA P = 0.09, linear trend P = 0.045). In addition, the changes of perfused capillary density at increasing MAP were inversely correlated with the basal perfused capillary density (R² = 0.95, P < 0.0001).

Conclusions

Patients with septic shock showed severe sublingual microcirculatory alterations that failed to improve with the increases in MAP with norepinephrine. Nevertheless, there was a considerable interindividual variation. Our results suggest that the increase in MAP above 65 mmHg is not an adequate approach to improve microcirculatory perfusion and might be harmful in some patients.     

Experimental study of sutureless colorectal anastomosis

BACKGROUND/AIMS: The present research project has been made mainly with the idea of comparing the tensile strength values and histological answers of three types of colon anastomosis: sutured with silk 5/0; polyglycolic acid 5/0; and sutureless anastomosis with human fibrin gum. METHODOLOGY: One hundred and five (105) Wistar breath rats allocated into 3 groups of 35 animals were used to implement this experimental research project: silk, polyglycolic acid and human fibrin gum. Furthermore, each group was subdivided in 5 series respectively to carry out an experimental study on the tensile strength parameter and anatomic-pathological determinations on the 10th, 20th, 30th, 40th and 50th day after the surgical intervention. The following surgical interventions were practiced on them: A cross section of the colon, followed by: group 1: an end-to-end discontinuous suture anastomosis with Silk; group 2: an end-to-end discontinuous suture anastomosis with polyglycolic acid; group 3: sutureless anastomosis with human fibrin gum. On the 10th, 20th, 30th, 40th and 50th days we proceeded to measure the anastomosis' tensile strength value for each series. We used a tensile strength apparatus and waited until the break down of the suture sample took place and wrote down the value, in g/cm, given by the voltmeter at that moment. RESULTS: The results obtained indicate that anastomosis made in group 1 (silk) lasted longer to the tensile strength apparatus; followed by those practiced in group 2 (polyglycolic acid); and finally anastomosis carried out in group 3 (human fibrin gum). However in the anastomotic process carried out with the human fibrin gum the healing started from the 10th day. In the same period of time we carried out the following anatomic-pathological determinations: a) sharp inflammation; b) edema; c) non-specific chronic inflammatory infiltrate; d) granulomatous inflammatory infiltrate to foreign bodies; e) fibrosis. CONCLUSIONS: The results show a better answer for anastomosis made with human fibrin gum than those carried out with the two other suture materials. This conclusion is based on the facts that the human fibrin gum used to carry out sutureless anastomosis during this research project generated a lower sharp inflammation and speediness in its absorption; absence of granular reaction to a foreign body; a minor or non-existent edema at all; as well as a good fibrous healing speediness process. Therefore, all these experimental results lead us to conclude that the human fibrin gum used to carry out sutureless anastomosis may be an alternative to the handmade conventional anastomosis. Moreover they are easy to be implemented.     

Biomarkers in lung oncology

The survival of advanced non-small-cell lung cancer patients is short in spite of advances in new combination chemotherapy regimens. The benefit of adding antiangiogenic drugs and/or EGFR inhibitors is unclear. For the vast majority of patients without EGFR mutations, treatment approaches based on customization should be pursued. BRCA1 is central to the repair of DNA damage and is an important modulator of the differential effect of chemotherapy. Retrospective and prospective data indicate that low BRCA1 mRNA levels predict better response and survival when patients are treated with cisplatin, non-taxane combinations.For an important subgroup of patients with EGFR mutations, selective treatment with EGFR tyrosine kinase inhibitors is a major advance, with a dramatic impact on clinical outcomes. In a prospective study of customized erlotinib [1], overall response rate was 70% (including 12% complete responses), median progression free survival was 14 months (even longer in women and in patients with del 19), 20% of patients were disease-free at three years, and median survival was 27 months. Nonetheless, these clinical outcomes fall short of curability and continuous treatment with erlotinib or gefitinib is required. It is plausible that several genetically defined subclasses of EGFR mutations could help to improve current clinical outcomes by combining erlotinib or gefitinib with other targeted drugs.     

Ethanol binging enhances hepatic microvascular responses to acetaminophen in mice

OBJECTIVE: Chronic alcoholism has been considered to be a risk for acetaminophen (APAP) hepatotoxicity, but little is known about the effect of binge alcohol drinking on APAP-induced liver injury. The present study was conducted to examine the effect of ethanol binging on APAP-induced hepatic microcirculatory dysfunction. METHODS: Male C57Bl/6 mice received 3 weekly ethanol binges (4 g/kg every 12 h x 5 doses/ week) or water binges. At 12 h after the last gavage, APAP (300 mg/kg) was given by oral gavage. In one group of mice, gadolinium chloride (GdCl3, 10 mg/kg) was intraperitoneally administered 2 and 1 days before the start of each weekly ethanol binge. RESULTS: Ethanol binging enhanced APAP-induced liver injury as indicated by ALT levels. Intravital microscopic study showed that APAP further increased the area occupied by infiltrated erythrocytes into the extrasinusoidal space as well as Kupffer cell phagocytic activity in ethanol-binged mice when compared with water-binged mice, while no significant differences in sinusoidal perfusion and leukocyte adhesion were observed. ALT levels after APAP were exacerbated in ethanol-binged mice treated with GdCl3, but APAP-induced hepatic microcirculatory dysfunction was not changed significantly. CONCLUSIONS: These results suggest that ethanol binging increases APAP-induced liver injury by exacerbating infiltration of the Disse space with blood cells. Kupffer cells exert a protective role in the liver against APAP intoxication following ethanol binging.