Marco Lattuada

Abdominal lymph flow in an endotoxin sepsis model: Influence of spontaneous breathing and mechanical ventilation

Objective:Lymph flow from the abdomen was investigated in a sepsis model. We also compared the effect on thoracic duct lymph flow of mechanical ventilation with different levels of positive end-expiratory pressure (PEEP) and spontaneous breathing with continuous positive airway pressure (CPAP). Design:Experimental study. Setting:Research laboratory in a university hospital. Subjects:Thirty-two pigs. Interventions:Animals were anesthetized. In study 1 (n = 18), an ultrasonic flow probe was put around the intact thoracic duct just caudal to the diaphragm, and animals were randomized to receive mechanical ventilation with a PEEP of 5 cm H2O or 15 cm H2O or breathed spontaneously in CPAP with a PEEP of 5 cm H2O. In study 2 (n = 6), the thoracic duct was cannulated and the cannula externalized through the abdominal wall for lymph collection; animals were then ventilated as in study 1. In all animals, endotoxin was infused at 15 &mgr;g/kg/hr for 2.5 hrs and then continued at 5 &mgr;g/kg/hr. In study 3, healthy (n = 4) and endotoxin-exposed (n = 4) pigs had intra-abdominal pressure increased to 27 cm H2O for 2 hrs by pneumoperitoneum. Lymph flow was measured as in study 1. Measurements and Main Results:Lymph flow (mean ± se) was 2.5 ± 0.4 mL/min at baseline and increased to 3.9 ± 0.8 mL/min after 90 mins and 6.3 ± 1.6 mL/min after 150 mins (p < .005) of endotoxin exposure. PEEP 15 cm H2O decreased lymph flow in pigs with intact thoracic duct (flow probe recording) and in pigs with cannulated lymph duct when drained against the central venous pressure. However, when drained against atmospheric pressure, PEEP increased flow. Spontaneous breathing increased flow both in intact and in cannulated animals. Conclusions:Endotoxin increases lymph flow from the abdomen. Mechanical ventilation with high PEEP impedes lymph drainage and could increase lymph production. Spontaneous breathing increases flow and improves drainage of abdominal edema.

Peak airway pressure increase is a late warning sign of partial endotracheal tube obstruction whereas change in expiratory flow is an early warning sign.

If peak inspiratory airway pressure (Ppeak) is used to monitor airway patency, progressive obstruction of the endotracheal tube (ETT) resulting from secretions can go undetected for a prolonged period. The reason is that any increase in Ppeak depends not only on the degree of narrowing but also on the inspiratory flow (&OV0312;) rate. Although the impact of narrowing on low inspiratory &OV0312; is small, its decelerating effect on the high expiratory &OV0312; is pronounced and, hence, easily detectable. Dividing the volume-flow curve of a passive expiration into five consecutive segments (slices) and calculating the time constants (&tgr;&Egr;) of these slices allows for analyzing whether and how expiratory &OV0312; is impeded by a partial obstruction. In nine piglets, during volume-controlled ventilation, three grades of ETT obstruction were created with an external clamp. In all animals the &tgr;E increased with ETT obstruction (mean for the first slice: 550 ms with unobstructed ETT; grade 1: 661; grade 2: 877; and grade 3: 1563 ms, respectively) and this increase was significant with grade 2 and 3 obstruction. Ppeak, by contrast, did not increase significantly (base: 13, grade 1: 14, grade 2: 15 cm H2O) until the most severe (grade 3: 20 cm H2O) obstruction was created. We conclude that partial obstruction of the ETT can be reliably monitored with the expiratory &OV0312; signal and has the potential of monitoring ETT narrowing in ventilator-dependent patients independent of the inspiratory &OV0312; pattern applied.

Lymphatic drainage between thorax and abdomen: please take good care of this well-performing machinery….

Abstract Introduction: Patients with sepsis often receive large amounts of fluids and the presence of capillary leak, trauma or bleeding results in ongoing fluid resuscitation. This increases interstitial and intestinal edema and finally leads to intra-abdominal hypertension (IAH), which in turn impedes lymphatic drainage. Patients with IAH often develop secondary respiratory failure needing mechanical ventilation with high intrathoracic pressure or PEEP that might further alter lymphatic drainage. This review will try to convince the reader of the importance of the lymphatics in septic patients with IAH. Methods: A Medline and PubMed literature search was performed using the terms “abdominal pressure”, “lymphatic drainage” and “ascites formation”. The references from these studies were searched for relevant articles that may have been missed in the primary search. These articles served as the basis for the recommendations below. Results: Induction of sepsis with lesion of the capillary alveolar barrier results in an increased water gradient between the capillaries and the interstitium in the lungs. The drainage flow to the thoracic duct is initially increased in order to protect the lung and maintain the pulmonary interstitium as dry as possible, however this results in increased intrathoracic pressure. Sepsis also increases the permeability of the capillaries in the splanchnic beds. In analogy to the lungs the lymphatic flow in the splanchnic areas increases together with the pressure inside as a physiological response in order to limit the increase in IAP. At a critical IAP level (around 20 cmH2O) the lymph flow starts to decrease and the splanchnic water content progressively increases. The lymph flow from the abdomen to the thorax is progressively decreased resulting in increased splanchnic water content and ascites formation. The presence of mechanical ventilation with high PEEP reduces the lymph drainage further which together with the increase in IAP decreases the lymphatic pressure gradient in the splanchnic regions, with a further increase in water content and IAP triggering a vicious cycle. Conclusion: Although often overlooked the role of lymphatic flow is complex but very important to determine not only the fluid balance in the lung but also in the peripheral organs. Different pathologies and treatments can markedly influence the pathophysiology of the lymphatics with dramatic effects on endorgan function.

Lymphatics and lymph in acute lung injury

Purpose of reviewLymph flow will be discussed as part of the drainage and fluid balance of lung tissue and abdomen as well as a qualitative analysis of inflammatory processes. Recent findingsMeasurement of lung lymph is still a technical challenge. Mechanical ventilation and positive end-expiratory pressure impede lung lymph flow by increased intrathoracic pressure and increased central venous pressure. Positive end-expiratory pressure may thus enhance edema formation of the lung. Inflammatory spread from abdomen to the lung via the lymphatic system has been shown in a number of experimental studies. Ligation or diversion of the thoracic duct has been proposed to blunt the effects of noxious stimuli mediated by lymphatics to the lungs. Lymphatics have a major role on abdominal fluid balance while draining extravascular fluid accumulation and edema, especially during sepsis. Mechanical ventilation with high airway pressure increases abdominal edema (ascites) and spontaneous breathing protects from edema formation. SummaryLymph flow measurements are still a difficult task to perform; however, new results show an important function in the fluid balance of the lung and abdomen. Inflammatory spread may occur from the lung to the periphery by the blood stream and from the abdomen to the lung by lymph flow.

Gas exchange in the ventilated patient.

Increased knowledge of the pathophysiologic mechanisms of impaired gas exchange during acute respiratory failure during recent years has stimulated many studies that evaluate different treatments to improve oxygenation and outcome. Changes in body position (mainly prone positioning) can significantly improve gas exchange in patients with acute respiratory distress syndrome and acute lung failure, with few complications related to the maneuver; however, no survival advantage has yet been detected. A correlation between aerated lung tissue and oxygenation also confirms the importance of recruitment maneuvers in improving gas exchange. Recent suggestions that recruitment of alveoli proceeds during most of the inspired vital capacity and not only around the lower inflection point of the pressure-volume curve raises the question how to best perform recruitment maneuvers. New data support the hypothesis that maintenance of even small amount of spontaneous breathing during mechanical ventilation (with airway pressure release ventilation or biphasic positive airway pressure) can improve gas exchange, whereas other unconventional ventilatory modes have not yet proved advantageous. Some mechanisms responsible for the high percentage of nonresponse to inhaled nitric oxide have recently been proposed, and combinations of inhaled nitric oxide with other therapies have been tested. Increased knowledge in this area may, in the future, make inhaled nitric oxide more attractive in the treatment of adult respiratory failure as well as in neonatal intensive care.

Distant effects of nitric oxide inhalation in endotoxemic pigs

Objective:Inhalation of nitric oxide (INO) has distant effects. By a blood– borne factor, INO down-regulates endogenous nitric oxide production in healthy pig lungs, resulting in vasoconstriction in lung regions not directly reached by INO. The aim of this study was to investigate whether INO has distant effects in endotoxemic pig lungs. The hypothesis was that INO down-regulates endogenous NO production in lung regions not reached by INO. Design:Prospective, randomized animal study. Setting:University hospital research laboratory. Subjects:Twenty-two pairs of domestic pigs. Interventions:Cross-circulation was established in 22 pairs of anesthetized pigs. Nine pairs received endotoxin (control group) and 13 pairs received endotoxin, with one pig inhaling NO (80 ppm) and one pig receiving blood from that pig (NO-blood recipient group). Measurements and Main Results:NO in exhaled air, NO synthase activity in lung tissue, endothelin-1 in the blood, ETA and ETB receptor immunoreactivity in lung tissue, vital parameters, and blood gases were measured. Endotoxin per se increased NO in exhaled air by 100% compared to baseline (control group). In the NO-blood recipient group, i.e., pigs receiving blood from the NO-inhaling pigs, NO in exhaled air increased by 300% (p = .03). The Ca2+-dependent NO synthase activity was higher in these pigs (p = .02), indicating increased endogenous NO production. The ET B receptor immunoreactivity was higher in the NO-blood recipient group (p = .004). Conclusions:As opposed to findings in healthy pigs, INO in endotoxemic pigs causes an increase in endogenous NO production in lung regions not reached by INO. Increased NO production in nonventilated lung regions may cause vasodilatation, counteracting the INO-induced increase in blood flow to the ventilated lung regions.

Evaluating abdominal oedema during experimental sepsis using an isotope technique

Purpose:  Abdominal oedema is common in sepsis. A technique for the study of such oedema may guide in the fluid regime of these patients.

Mechanical ventilation worsens abdominal edema and inflammation in porcine endotoxemia.

IntroductionWe hypothesized that mechanical ventilation per se increases abdominal edema and inflammation in sepsis and tested this in experimental endotoxemia.MethodsThirty anesthetized piglets were allocated to one of five groups: healthy control pigs breathing spontaneously with continuous positive pressure of 5 cm H2O or mechanically ventilated with positive end-expiratory pressure of 5 cm H2O, and endotoxemic piglets during mechanical ventilation for 2.5 hours and then continued on mechanical ventilation with positive end-expiratory pressure of either 5 or 15 cm H2O or switched to spontaneous breathing with continuous positive pressure of 5 cm H2O for another 2.5 hours. Abdominal edema formation was estimated by isotope technique, and inflammatory markers were measured in liver, intestine, lung, and plasma.ResultsHealthy controls: 5 hours of spontaneous breathing did not increase abdominal fluid, whereas mechanical ventilation did (Normalized Index increased from 1.0 to 1.6; 1 to 3.3 (median and range, P < 0.05)). Endotoxemic animals: Normalized Index increased almost sixfold after 5 hours of mechanical ventilation (5.9; 4.9 to 6.9; P < 0.05) with twofold increase from 2.5 to 5 hours whether positive end-expiratory pressure was 5 or 15, but only by 40% with spontaneous breathing (P < 0.05 versus positive end-expiratory pressure of 5 or 15 cm H2O). Tumor necrosis factor-α (TNF-α) and interleukin (IL)-6 in intestine and liver were 2 to 3 times higher with mechanical ventilation than during spontaneous breathing (P < 0.05) but similar in plasma and lung. Abdominal edema formation and TNF-α in intestine correlated inversely with abdominal perfusion pressure.ConclusionsMechanical ventilation with positive end-expiratory pressure increases abdominal edema and inflammation in intestine and liver in experimental endotoxemia by increasing systemic capillary leakage and impeding abdominal lymph drainage.