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IMPORTANCE: Maneuvers assessing fluid responsiveness before an intravascular volume expansion may limit useless fluid administration, which in turn may improve outcomes. OBJECTIVE: To describe maneuvers for assessing fluid responsiveness in mechanically ventilated patients. REGISTRATION: The protocol was registered at PROSPERO: CRD42019146781. INFORMATION SOURCES AND SEARCH: PubMed, EMBASE, CINAHL, SCOPUS, and Web of Science were search from inception to 08/08/2023. STUDY SELECTION AND DATA COLLECTION: Prospective and intervention studies were selected. STATISTICAL ANALYSIS: Data for each maneuver were reported individually and data from the five most employed maneuvers were aggregated. A traditional and a Bayesian meta-analysis approach were performed. RESULTS: A total of 69 studies, encompassing 3185 fluid challenges and 2711 patients were analyzed. The prevalence of fluid responsiveness was 49.9%. Pulse pressure variation (PPV) was studied in 40 studies, mean threshold with 95% confidence intervals (95% CI) = 11.5 (10.5-12.4)%, and area under the receiver operating characteristics curve (AUC) with 95% CI was 0.87 (0.84-0.90). Stroke volume variation (SVV) was studied in 24 studies, mean threshold with 95% CI = 12.1 (10.9-13.3)%, and AUC with 95% CI was 0.87 (0.84-0.91). The plethysmographic variability index (PVI) was studied in 17 studies, mean threshold = 13.8 (12.3-15.3)%, and AUC was 0.88 (0.82-0.94). Central venous pressure (CVP) was studied in 12 studies, mean threshold with 95% CI = 9.0 (7.7-10.1) mmHg, and AUC with 95% CI was 0.77 (0.69-0.87). Inferior vena cava variation (∆IVC) was studied in 8 studies, mean threshold = 15.4 (13.3-17.6)%, and AUC with 95% CI was 0.83 (0.78-0.89). CONCLUSIONS: Fluid responsiveness can be reliably assessed in adult patients under mechanical ventilation. Among the five maneuvers compared in predicting fluid responsiveness, PPV, SVV, and PVI were superior to CVP and ∆IVC. However, there is no data supporting any of the above mentioned as being the best maneuver. Additionally, other well-established tests, such as the passive leg raising test, end-expiratory occlusion test, and tidal volume challenge, are also reliable.
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Pressão Venosa Central , Hidratação , Pletismografia , Respiração Artificial , Volume Sistólico , Veia Cava Inferior , Humanos , Respiração Artificial/métodos , Respiração Artificial/estatística & dados numéricos , Pressão Venosa Central/fisiologia , Hidratação/métodos , Hidratação/normas , Hidratação/estatística & dados numéricos , Veia Cava Inferior/fisiologia , Volume Sistólico/fisiologia , Pletismografia/métodos , Pressão Sanguínea/fisiologiaRESUMO
OBJECTIVES: To investigate the effects of immediate start of norepinephrine versus initial fluid loading followed by norepinephrine on macro hemodynamics, regional splanchnic and intestinal microcirculatory flows in endotoxic shock. DESIGN: Animal experimental study. SETTING: University translational research laboratory. SUBJECTS: Fifteen Landrace pigs. INTERVENTIONS: Shock was induced by escalating dose of lipopolysaccharide. Animals were allocated to immediate start of norepinephrine (i-NE) ( n = 6) versus mandatory 1-hour fluid loading (30 mL/kg) followed by norepinephrine (i-FL) ( n = 6). Once mean arterial pressure greater than or equal to 75 mm Hg was, respectively, achieved, successive mini-fluid boluses of 4 mL/kg of Ringer Lactate were given whenever: a) arterial lactate greater than 2.0 mmol/L or decrease less than 10% per 30 min and b) fluid responsiveness was judged to be positive. Three additional animals were used as controls (Sham) ( n = 3). Time × group interactions were evaluated by repeated-measures analysis of variance. MEASUREMENTS AND MAIN RESULTS: Hypotension was significantly shorter in i-NE group (7.5 min [5.5-22.0 min] vs 49.3 min [29.5-60.0 min]; p < 0.001). Regional mesenteric and microcirculatory flows at jejunal mucosa and serosa were significantly higher in i-NE group at 4 and 6 hours after initiation of therapy ( p = 0.011, p = 0.032, and p = 0.017, respectively). Misdistribution of intestinal microcirculatory blood flow at the onset of shock was significantly reversed in i-NE group ( p < 0.001), which agreed with dynamic changes in mesenteric-lactate levels ( p = 0.01) and venous-to-arterial carbon dioxide differences ( p = 0.001). Animals allocated to i-NE showed significantly higher global end-diastolic volumes ( p = 0.015) and required significantly less resuscitation fluids ( p < 0.001) and lower doses of norepinephrine ( p = 0.001) at the end of the experiment. Pulmonary vascular permeability and extravascular lung water indexes were significantly lower in i-NE group ( p = 0.021 and p = 0.004, respectively). CONCLUSIONS: In endotoxemic shock, immediate start of norepinephrine significantly improved regional splanchnic and intestinal microcirculatory flows when compared with mandatory fixed-dose fluid loading preceding norepinephrine. Immediate norepinephrine strategy was related with less resuscitation fluids and lower vasopressor doses at the end of the experiment.
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Norepinefrina , Choque Séptico , Animais , Suínos , Norepinefrina/uso terapêutico , Microcirculação , Circulação Esplâncnica , Vasoconstritores/farmacologia , Vasoconstritores/uso terapêutico , Choque Séptico/tratamento farmacológico , Hemodinâmica , Lactatos/farmacologia , Lactatos/uso terapêuticoRESUMO
Background: Microvascular lung vessels obstructive thromboinflammatory syndrome has been proposed as a possible mechanism of respiratory failure in COVID-19 patients. However, it has only been observed in post-mortem studies and has never been documented in vivo, probably because of a lack of CT scan sensitivity in small pulmonary arteries. The aim of the present study was to assess the safety, tolerability, and diagnostic value of optical coherence tomography (OCT) for the assessment of patients with COVID-19 pneumonia for pulmonary microvascular thromboinflammatory syndrome. Methods: The COVID-OCT trial was a multicenter, open-label, prospective, interventional clinical study. Two cohorts of patients were included in the study and underwent pulmonary OCT evaluation. Cohort A consisted of patients with COVID-19 with a negative CT scan for pulmonary thrombosis and elevated thromboinflammatory markers (D-dimer > 10,000 ng/mL or 5,000 < D-dimer < 10,000 ng/mL and one of: C-reactive Protein > 100 mg/dL, IL-6 > 6 pg/mL, or ferritin > 900 ng/L). Cohort B consisted of patients with COVID-19 and a CT scan positive for pulmonary thrombosis. The primary endpoints of the study were: (i) to evaluate the overall safety of OCT investigation in patients with COVID-19 pneumonia, and (ii) to report on the potential value of OCT as a novel diagnostic tool for the diagnosis of microvascular pulmonary thrombosis in COVID-19 patients. Results: A total of 13 patients were enrolled. The mean number of OCT runs performed in each patient was 6.1 ± 2.0, both in ground glass and healthy lung areas, achieving a good evaluation of the distal pulmonary arteries. Overall, OCT runs identified microvascular thrombosis in 8 patients (61.5%): 5 cases of red thrombus, 1 case of white thrombus, and 2 cases of mixed thrombus. In Cohort A, the minimal lumen area was 3.5 ± 4.6 mm2, with stenosis of 60.9 ± 35.9% of the area, and the mean length of thrombus-containing lesions was 5.4 ± 3.0 mm. In Cohort B, the percentage area obstruction was 92.6 ± 2.6, and the mean thrombus-containing lesion length was 14.1 ± 13.9 mm. No peri-procedural complications occurred in any of the 13 patients. Conclusion: OCT appears to be a safe and accurate method of evaluating the distal pulmonary arteries in hospitalized COVID-19 patients. Here, it enabled the first in vivo documentation of distal pulmonary arterial thrombosis in patients with elevated thromboinflammatory markers, even when their CT angiogram was negative for pulmonary thrombosis. Clinical trial registration: ClinicalTrial.gov, identifier NCT04410549.
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BACKGROUND: Ventilation/perfusion inequalities impair gas exchange in acute respiratory distress syndrome (ARDS). Although increased dead-space ventilation (VD/VT) has been described in ARDS, its mechanism is not clearly understood. We sought to evaluate the relationships between dynamic variations in VD/VT and extra-pulmonary microcirculatory blood flow detected at sublingual mucosa hypothesizing that an altered microcirculation, which is a generalized phenomenon during severe inflammatory conditions, could influence ventilation/perfusion mismatching manifested by increases in VD/VT fraction during early stages of ARDS. METHODS: Forty-two consecutive patients with early moderate and severe ARDS were included. PEEP was set targeting the best respiratory-system compliance after a PEEP-decremental recruitment maneuver. After 60 min of stabilization, hemodynamics and respiratory mechanics were recorded and blood gases collected. VD/VT was calculated from the CO2 production ([Formula: see text]) and CO2 exhaled fraction ([Formula: see text]) measurements by volumetric capnography. Sublingual microcirculatory images were simultaneously acquired using a sidestream dark-field device for an ulterior blinded semi-quantitative analysis. All measurements were repeated 24 h after. RESULTS: Percentage of small vessels perfused (PPV) and microcirculatory flow index (MFI) were inverse and significantly related to VD/VT at baseline (Spearman's rho = - 0.76 and - 0.63, p < 0.001; R2 = 0.63, and 0.48, p < 0.001, respectively) and 24 h after (Spearman's rho = - 0.71, and - 0.65; p < 0.001; R2 = 0.66 and 0.60, p < 0.001, respectively). Other respiratory, macro-hemodynamic and oxygenation parameters did not correlate with VD/VT. Variations in PPV between baseline and 24 h were inverse and significantly related to simultaneous changes in VD/VT (Spearman's rho = - 0.66, p < 0.001; R2 = 0.67, p < 0.001). CONCLUSION: Increased heterogeneity of microcirculatory blood flow evaluated at sublingual mucosa seems to be related to increases in VD/VT, while respiratory mechanics and oxygenation parameters do not. Whether there is a cause-effect relationship between microcirculatory dysfunction and dead-space ventilation in ARDS should be addressed in future research.
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BACKGROUND: Optimal timing for the start of vasopressors (VP) in septic shock has not been widely studied since it is assumed that fluids must be administered in advance. We sought to evaluate whether a very early start of VP, even without completing the initial fluid loading, might impact clinical outcomes in septic shock. METHODS: A total of 337 patients with sepsis requiring VP support for at least 6 h were initially selected from a prospectively collected database in a 90-bed mixed-ICU during a 24-month period. They were classified into very-early (VE-VPs) or delayed vasopressor start (D-VPs) categories according to whether norepinephrine was initiated or not within/before the next hour of the first resuscitative fluid load. Then, VE-VPs (n = 93) patients were 1:1 propensity matched to D-VPs (n = 93) based on age; source of admission (emergency room, general wards, intensive care unit); chronic and acute comorbidities; and lactate, heart rate, systolic, and diastolic pressure at vasopressor start. A risk-adjusted Cox proportional hazard model was fitted to assess the association between VE-VPs and day 28 mortality. Finally, a sensitivity analysis was performed also including those patients requiring VP support for less than 6 h. RESULTS: Patients subjected to VE-VPs received significantly less resuscitation fluids at vasopressor starting (0[0-510] vs. 1500[650-2300] mL, p < 0.001) and during the first 8 h of resuscitation (1100[500-1900] vs. 2600[1600-3800] mL, p < 0.001), with no significant increase in acute renal failure and/or renal replacement therapy requirements. VE-VPs was related with significant lower net fluid balances 8 and 24 h after VPs. VE-VPs was also associated with a significant reduction in the risk of death compared to D-VPs (HR 0.31, CI95% 0.17-0.57, p < 0.001) at day 28. Such association was maintained after including patients receiving vasopressors for < 6 h. CONCLUSION: A very early start of vasopressor support seems to be safe, might limit the amount of fluids to resuscitate septic shock, and could lead to better clinical outcomes.
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Hidratação , Norepinefrina , Choque Séptico , Vasoconstritores , Injúria Renal Aguda/complicações , Idoso , Feminino , Humanos , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Norepinefrina/administração & dosagem , Terapia de Substituição Renal , Choque Séptico/tratamento farmacológico , Fatores de Tempo , Vasoconstritores/administração & dosagemRESUMO
BACKGROUND: Appropriate use of antimicrobials is essential to improve outcomes in sepsis. The aim of this study was to determine whether the use of a rapid molecular blood test-SeptiFast (SF) reduces the antibiotic consumption through early de-escalation in patients with nosocomial sepsis compared with conventional blood cultures (BCs). METHODS: This was a prospective, randomized, superiority, controlled trial conducted at Sao Paulo Heart Institute in the period October 2012-May 2016. Adult patients admitted to the hospital for at least 48 h with a diagnosis of nosocomial sepsis underwent microorganism identification by both SF test and BCs. Patients randomized into the intervention group received antibiotic therapy adjustment according to the results of SF. Patients randomized into the control group received standard antibiotic adjustment according to the results of BCs. The primary endpoint was antimicrobial consumption during the first 14 days after randomization. RESULTS: A total of 200 patients were included (100 in each group). The intention to treat analysis found no significant differences in median antibiotic consumption. In the subgroup of patients with positive SF and blood cultures (19 and 25 respectively), we found a statistically significant reduction in the median antimicrobial consumption which was 1429 (1071-2000) days of therapy (DOT)/1000 patients-day in the intervention group and 1889 (1357-2563) DOT/1000 patients-day in the control group (p = 0.017), in the median time of antimicrobial de-escalation (8 versus 54 h-p < 0.001), in the duration of antimicrobial therapy (p = 0.039) and in anti-gram-positive antimicrobial costs (p = 0.002). Microorganism identification was possible in 24.5% of patients (45/184) by SF and 21.2% (39/184) by BC (p = 0.45). CONCLUSION: This randomized clinical trial showed that the use of a rapid molecular-based pathogen identification test does not reduce the median antibiotic consumption in nosocomial sepsis. However, in patients with positive microbiological tests, the use of SeptiFast reduced antimicrobial consumption through early de-escalation compared to conventional blood cultures. These results were driven by a reduction in the consumption of antimicrobials used for Gram-positive bacteria. TRIAL REGISTRATION: The trial was registered at ClinicalTrials.gov (NCT01450358) on 12th October 2011.
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PURPOSE: Septic shock has been associated with microvascular alterations and these in turn with the development of organ dysfunction. Despite advances in video microscopic techniques, evaluation of microcirculation at the bedside is still limited. Venous-to-arterial carbon dioxide difference (Pv-aCO2) may be increased even when venous O2 saturation (SvO2) and cardiac output look normal, which could suggests microvascular derangements. We sought to evaluate whether Pv-aCO2 can reflect the adequacy of microvascular perfusion during the early stages of resuscitation of septic shock. METHODS: Prospective observational study including 75 patients with septic shock in a 60-bed mixed ICU. Arterial and mixed-venous blood gases and hemodynamic variables were obtained at catheter insertion (T0) and 6 h after (T6). Using a sidestream dark-field device, we simultaneously acquired sublingual microcirculatory images for blinded semiquantitative analysis. Pv-aCO2 was defined as the difference between mixed-venous and arterial CO2 partial pressures. RESULTS: Progressively lower percentages of small perfused vessels (PPV), lower functional capillary density, and higher heterogeneity of microvascular blood flow were observed at higher Pv-aCO2 values at both T0 and T6. Pv-aCO2 was significantly correlated to PPV (T0: coefficient -5.35, 95 % CI -6.41 to -4.29, p < 0.001; T6: coefficient, -3.49, 95 % CI -4.43 to -2.55, p < 0.001) and changes in Pv-aCO2 between T0 and T6 were significantly related to changes in PPV (R (2) = 0.42, p < 0.001). Absolute values and changes in Pv-aCO2 were not related to global hemodynamic variables. Good agreement between venous-to-arterial CO2 and PPV was maintained even after corrections for the Haldane effect. CONCLUSIONS: During early phases of resuscitation of septic shock, Pv-aCO2 could reflect the adequacy of microvascular blood flow.
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Artérias/fisiopatologia , Dióxido de Carbono/sangue , Microcirculação/fisiologia , Choque Séptico/fisiopatologia , Veias/fisiopatologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Gasometria , Colômbia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos ProspectivosRESUMO
Descrevemos o caso de um paciente com hematoma intramural e trombo flutuante após ressuscitação cardiopulmonar. Esse homem, de 92 anos de idade, teve uma parada cardíaca causada por fibrilação atrial e testemunhas iniciaram imediatamente manobras manuais de ressuscitação cardiopulmonar. Ao ser admitido no hospital, o paciente apresentava-se em choque cardiogênico, sendo, então, imediatamente submetido a ecocardiografia transesofágica. Além de uma parede anterior acinética, o exame da aorta torácica descendente mostrou um hematoma intramural e um trombo intra-aórtico flutuante a uma distância de 40cm do arco dental. Não havia dissecção da aorta. O trombo foi atribuído à compressão aórtica durante a ressuscitação cardiopulmonar. Embora o trombo aórtico e o hematoma intramural não tenham se associado a qualquer complicação nesse paciente, a inserção de um balão intra-aórtico poderia ter levado a uma ruptura da aorta ou a eventos embólicos. Recomenda-se a realização de ecocardiografia transesofágica, quando disponível, antes da inserção de um balão intra-aórtico de contrapulsação em pacientes submetidos à ressuscitação cardiopulmonar.
We describe the case of a patient with an intramural hematoma and floating thrombus after cardiopulmonary resuscitation. The 92-year old man had a cardiac arrest due to ventricular fibrillation and witnesses immediately initiated manual cardiopulmonary resuscitation. Transesophageal echocardiography was performed immediately on hospital admission because the patient was in cardiogenic shock. In addition to an akinetic anterior wall, examination of the descending thoracic aorta demonstrated an intramural hematoma and a floating intra-aortic thrombus at a distance of 40cm from the dental arch. There was no aortic dissection. The thrombus was attributed to aortic compression during cardiopulmonary resuscitation. Although the aortic thrombus and intramural hematoma were not associated with any complications in this patient, insertion of an intra-aortic balloon may have led to aortic rupture or embolic events. Transesophageal echocardiography should be performed, when available, prior to insertion of an intra-aortic balloon for counterpulsation in patients who have undergone cardiopulmonary resuscitation.
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Idoso de 80 Anos ou mais , Humanos , Masculino , Doenças da Aorta/etiologia , Reanimação Cardiopulmonar/efeitos adversos , Hematoma/etiologia , Trombose/etiologia , Aorta Torácica/patologia , Doenças da Aorta/patologia , Reanimação Cardiopulmonar/métodos , Ecocardiografia Transesofagiana/métodos , Parada Cardíaca/etiologia , Parada Cardíaca/terapia , Hematoma/patologia , Trombose/patologia , Fibrilação Ventricular/complicaçõesRESUMO
We describe the case of a patient with an intramural hematoma and floating thrombus after cardiopulmonary resuscitation. The 92-year old man had a cardiac arrest due to ventricular fibrillation and witnesses immediately initiated manual cardiopulmonary resuscitation. Transesophageal echocardiography was performed immediately on hospital admission because the patient was in cardiogenic shock. In addition to an akinetic anterior wall, examination of the descending thoracic aorta demonstrated an intramural hematoma and a floating intra-aortic thrombus at a distance of 40cm from the dental arch. There was no aortic dissection. The thrombus was attributed to aortic compression during cardiopulmonary resuscitation. Although the aortic thrombus and intramural hematoma were not associated with any complications in this patient, insertion of an intra-aortic balloon may have led to aortic rupture or embolic events. Transesophageal echocardiography should be performed, when available, prior to insertion of an intra-aortic balloon for counterpulsation in patients who have undergone cardiopulmonary resuscitation.
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Doenças da Aorta/etiologia , Reanimação Cardiopulmonar/efeitos adversos , Hematoma/etiologia , Trombose/etiologia , Idoso de 80 Anos ou mais , Aorta Torácica/patologia , Doenças da Aorta/patologia , Reanimação Cardiopulmonar/métodos , Ecocardiografia Transesofagiana/métodos , Parada Cardíaca/etiologia , Parada Cardíaca/terapia , Hematoma/patologia , Humanos , Masculino , Trombose/patologia , Fibrilação Ventricular/complicaçõesRESUMO
Shock is characterized by an alteration in tissue perfusion that may lead to tissue hypoxia. Recent guidelines recommend aggressive and early resuscitation therapy, but mortality rate is still unacceptably high. Unfortunately, traditional clinical surrogates used to guide resuscitation therapy poorly correlate with microcirculatory blood flow, a key determinant of tissue perfusion. New techniques that directly assess microcirculatory perfusion at the bedside have emerged as a complement to traditional macrohemodynamic parameters. These techniques have been supported by several studies showing microcirculatory alterations in different clinical settings. In addition, these microcirculatory alterations are related with outcome and persist regardless of arterial pressure normalization, being a better predictor of organ dysfunction and mortality than global hemodynamic and laboratory parameters. These findings allowed the concept of "microcirculatory-goal directed therapy", which is now in its preliminary phase, as the impact of many interventions still needs to be assessed. Finally, microcirculation assessment has also been explored in other medical s such as perioperative, systemic arterial hypertension, heart failure, and hyperviscosity syndromes. In this review, we shortly present the characteristics of microcirculation and the main determinants of capillary blood flow, and we discuss advantages and limitations of some recently available techniques to evaluate microcirculation at the bedside, and how they could be useful for the general clinician in daily practice.
O choque é caracterizado por uma alteração na perfusão tecidual que pode levar à hipóxia tecidual. Diretrizes recentes recomendam uma terapia de ressuscitação hemodinâmica precoce e agressiva nos estados de choque, mas a taxa de mortalidade ainda é inaceitavelmente alta. Os parâmetros clínicos habituais usados para orientar a terapia de reanimação correlacionam-se mal com o fluxo sanguíneo capilar, um determinante essencial da perfusão tecidual. Novas técnicas que avaliam diretamente a perfusão da microcirculação à beira do leito surgem como um complemento aos parâmetros macro-hemodinâmicos tradicionais. Estas técnicas foram testadas em vários estudos que mostraram alterações microcirculatórias em diferentes situações clínicas de choque. Além disso, estas alterações microcirculatórias estão relacionadas ao prognóstico, e persistem independentemente da normalização da pressão arterial, sendo um melhor preditor de disfunção orgânica e mortalidade do que os parâmetros hemodinâmicos globais e laboratoriais. Estes achados permitiram lançar o conceito de "terapia dirigida por parâmetros microcirculatórios", atualmente em fase preliminar, uma vez que o impacto de muitas intervenções ainda precisa ser avaliado. Finalmente, a avaliação da microcirculação também foi explorada em outras áreas que não o choque, como o período perioperatório, hipertensão arterial sistêmica, insuficiência cardíaca e síndromes de hiperviscosidade. Nesta revisão, apresentamos sucintamente as características da microcirculação e os principais determinantes do fluxo sanguíneo capilar e discutimos as vantagens e limitações de algumas tecnologias recentes disponíveis para avaliar a microcirculação à beira do leito e como podem ser úteis ao clínico geral na prática diária.
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BACKGROUND: Dobutamine is the agent of choice for increasing cardiac output during myocardial depression in humans with septic shock. Studies have shown that beta-adrenoceptor agonists influence nitric oxide generation, probably by modulating cyclic adenosine monophosphate. We investigated the effects of dobutamine on the systemic and luminal gut release of nitric oxide during endotoxic shock in rabbits. MATERIAL/METHODS: Twenty anesthetized and ventilated New Zealand rabbits received placebo or intravenous lipopolysaccharide with or without dobutamine (5 micro g/kg/min). Ultrasonic flow probes placed around the superior mesenteric artery and the abdominal aorta continuously estimated the flow. A segment from the ileum was isolated and perfused, and serum nitrate/nitrite levels were measured in the perfusate solution and the serum every hour. RESULTS: The mean arterial pressure decreased with statistical significance in the lipopolysaccharide group but not in the lipopolysaccharide/dobutamine group. The abdominal aortic flow decreased statistically significantly after lipopolysaccharide administration in both groups but recovered to baseline in the lipopolysaccharide/dobutamine group. The flow in the superior mesenteric artery was statistically significantly higher in the lipopolysaccharide/dobutamine group than in the lipopolysaccharide group at 2 hours. The serum nitrate/nitrite levels were higher in the lipopolysaccharide group and lower in the lipopolysaccharide/dobutamine group than those in the control group. The gut luminal perfusate serum nitrate/nitrite level was higher in the lipopolysaccharide group than in the lipopolysaccharide/dobutamine group. CONCLUSIONS: Dobutamine can decrease total and intestinal nitric oxide production in vivo. Those effects seem to be inversely proportional to the changes in blood flow.
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Dobutamina/farmacologia , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/metabolismo , Óxido Nítrico/biossíntese , Choque Séptico/metabolismo , Animais , Circulação Coronária/efeitos dos fármacos , Frequência Cardíaca/efeitos dos fármacos , Ácido Láctico/sangue , Lipopolissacarídeos/administração & dosagem , Lipopolissacarídeos/farmacologia , Nitratos/sangue , Nitritos/sangue , Perfusão , Coelhos , Choque Séptico/fisiopatologiaRESUMO
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.
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Enterite/tratamento farmacológico , Fenantrenos/farmacologia , Pneumonia Bacteriana/tratamento farmacológico , Inibidores de Poli(ADP-Ribose) Polimerases , Sepse/tratamento farmacológico , Animais , Aorta , Pressão Sanguínea , Enterite/microbiologia , Inibidores Enzimáticos/farmacologia , Intestinos/irrigação sanguínea , Intestinos/microbiologia , Intestinos/patologia , Artéria Mesentérica Superior , Pneumonia Bacteriana/complicações , Pneumonia Bacteriana/microbiologia , Infecções por Pseudomonas/tratamento farmacológico , Infecções por Pseudomonas/etiologia , Pseudomonas aeruginosa/isolamento & purificação , Coelhos , Fluxo Sanguíneo Regional , Sepse/microbiologia , Organismos Livres de Patógenos Específicos , TraqueiaRESUMO
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."