Rudolf Hering

Effects of mechanical ventilation on release of cytokines into systemic circulation in patients with normal pulmonary function.

BackgroundMechanical ventilation with high tidal volumes (VT) in contrast to mechanical ventilation with low VT has been shown to increase plasma levels of proinflammatory and antiinflammatory mediators in patients with acute lung injury. The authors hypothesized that, in patients without previous lung injury, a conventional potentially injurious ventilatory strategy with high VT and zero end-expiratory pressure (ZEEP) will not cause a cytokine release into systemic circulation. MethodsA total of 39 patients with American Society of Anesthesiologists physical status I–II and without signs of systemic infection scheduled for elective surgery with general anesthesia were randomized to receive mechanical ventilation with either (1) VT = 15 ml/kg ideal body weight on ZEEP, (2) VT = 6 ml/kg ideal body weight on ZEEP, or (3) VT = 6 ml/kg ideal body weight on positive end-expiratory pressure of 10 cm H2O. Plasma levels of proinflammatory and antiinflammatory mediators tumor necrosis factor, interleukin (IL)-6, IL-10, and IL-1 receptor antagonist were determined before and 1 h after the initiation of mechanical ventilation. ResultsPlasma levels of all cytokines remained low in all settings. IL-6, tumor necrosis factor, and IL-1 receptor antagonist did not change significantly after 1 h of mechanical ventilation. IL-10 was below the detection limit (10 pg/ml) in 35 of 39 patients. There were no differences between groups. ConclusionsInitiation of mechanical ventilation for 1 h in patients without previous lung injury caused no consistent changes in plasma levels of studied mediators. Mechanical ventilation with high VT on ZEEP did not result in higher cytokine levels compared with lung-protective ventilatory strategies. Previous lunge damage seems to be mandatory to cause an increase in plasma cytokines after 1 h of high VT mechanical ventilation.

The effects of prone positioning on intraabdominal pressure and cardiovascular and renal function in patients with acute lung injury.

To detect any harmful effects of prone positioning on intraabdominal pressure (IAP) and cardiovascular and renal function, we studied 16 mechanically ventilated patients with acute lung injury randomly in prone and supine positions, without minimizing the restriction of the abdomen. Effective renal blood flow index and glomerular filtration rate index were determined by the paraaminohippurate and inulin clearance techniques. Prone positioning resulted in an increase in IAP from 12 ± 4 to 14 ± 5 mm Hg (P < 0.05), Pao2/fraction of inspired oxygen from 220 ± 91 to 267 ± 82 mm Hg (P < 0.05), cardiac index from 4.1 ± 1.1 to 4.4 ± 0.7 L/min (P < 0.05), mean arterial pressure from 77 ± 10 to 82 ± 11 mm Hg (P < 0.01), and oxygen delivery index from 600 ± 156 to 648 ± 95 mL · min−1 · m−2 (P < 0.05). Renal fraction of cardiac output decreased from 19.1% ± 12.5% to 15.5% ± 8.8% (P < 0.05), and renal vascular resistance index increased from 11762 ± 6554 dynes · s · cm−5 · m2 to 15078 ± 10594 dynes · s · cm−5 · m2 (P < 0.05), whereas effective renal blood flow index, glomerular filtration rate index, filtration fraction, urine volume, fractional sodium excretion, and osmolar and free water clearances remained constant during prone positioning. Prone positioning, when used in patients with acute lung injury, although it is associated with a small increase in IAP, contributes to improved arterial oxygenation and systemic blood flow without affecting renal perfusion and function. Apparently, special support to allow free chest and abdominal movement seems unnecessary when mechanically ventilated, hemodynamically stable patients without abdominal hypertension are proned to improve gas exchange.

The hypothalamic-pituitary-adrenal axis of patients with severe sepsis: altered response to corticotropin-releasing hormone.

ObjectiveTo investigate the functional integrity of the hypothalamic-pituitary-adrenal (HPA) axis in patients with severe sepsis by stimulating with corticotropin-releasing hormone (CRH). DesignProspective observational study in consecutive intensive care unit patients with severe sepsis. SettingSurgical intensive care unit and outpatient department of endocrinology in a university hospital. PatientsThe study included 20 patients with the diagnosis of severe sepsis; six critically ill, nonseptic patients after major surgery; ten patients with primary adrenal insufficiency; ten patients with anterior pituitary insufficiency; and ten individuals without clinical signs of HPA axis disturbance. InterventionsCRH tests were performed with an intravenous bolus injection of 100 &mgr;g of human CRH. Measurements and Main Results We studied the functional integrity of the HPA axis in patients with severe sepsis by performing the CRH test. In addition, during the period of severe sepsis, we repeatedly measured basal plasma concentrations of adrenocorticotropin hormone (ACTH) and cortisol. The mean basal plasma cortisol concentration was decreased significantly in nonsurvivors with severe sepsis (288.8 ± 29.1 [sem] nmol/L) compared with survivors (468.1± 18.6 nmol/L;p < .01). By calculating the ACTH/cortisol indices, we found no evidence for adrenal insufficiency in patients with severe sepsis. The mean ACTH/cortisol indices of nonsurvivors with severe sepsis (0.02 ± 0.008) and survivors (0.01 ± 0.002) were significantly lower compared with the index of patients with primary adrenal insufficiency (6.8 ± 1.0;p < .001). In contrast, in nonsurvivors with severe sepsis, the plasma cortisol response to CRH stimulation was impaired compared with survivors: The mean basal cortisol concentration within the CRH test was 269.4 ± 39.8 nmol/L in nonsurvivors compared with 470.8 ± 48.4 nmol/L in survivors and increased to a peak value of 421.6 ± 72.6 nmol/L in nonsurvivors and 680.7 ± 43.8 nmol/L in survivors (p < .02). However, the change in plasma cortisol, expressed as mean ± sem and calculated by subtracting the basal cortisol from the peak cortisol after CRH stimulation, was not significantly different in survivors with severe sepsis (243.5 ± 36.1, range 111.0–524.0 nmol/L, n = 15) compared with nonsurvivors (161.0 ± 38.9, range 42.0–245.0 nmol/L, n = 5;p > .05). ConclusionsWe found lower basal plasma cortisol concentrations in nonsurvivors compared with survivors of severe sepsis. In addition, the plasma cortisol response to a single CRH stimulation was impaired in nonsurvivors compared with survivors. Reduced responses to CRH stimulation may reflect a state of endocrinologic organ dysfunction in severe sepsis.

Fetoscopic and ultrasound‐guided decompression of the fetal trachea in a human fetus with Fraser syndrome and congenital high airway obstruction syndrome (CHAOS) from laryngeal atresia

Congenital high airway obstruction syndrome (CHAOS) from laryngeal atresia bears a poor prognosis for hydropic fetuses owing to cardiac failure. We attempted percutaneous fetoscopic and ultrasound‐guided tracheal decompression in a hydropic human fetus with CHAOS associated with Fraser syndrome.

Effects of spontaneous breathing during airway pressure release ventilation on intestinal blood flow in experimental lung injury.

Background In critical illness, the gut is susceptible to hypoperfusion and hypoxia. Positive-pressure ventilation can affect systemic hemodynamics and regional blood flow distribution, with potentially deleterious effects on the intestinal circulation. The authors hypothesized that spontaneous breathing (SB) with airway pressure release ventilation (APRV) provides better systemic and intestinal blood flow than APRV without SB. Methods Twelve pigs with oleic acid–induced lung injury received APRV with and without SB. When SB was abolished, either the tidal volume or the ventilator rate was increased to maintain pH and arterial carbon dioxide tension constant as compared to APRV with SB. Systemic hemodynamics were determined by double indicator dilution. Blood flow to the intestinal mucosa–submucosa and muscularis–serosa was measured using colored microspheres. Results Systemic blood flow increased during APRV with SB. During APRV with SB, mucosal–submucosal blood flow (ml · g−1 · min−1) was 0.39 ± 0.21 in the stomach, 0.76 ± 0.35 in the duodenum, 0.71 ± 0.35 in the jejunum, 0.71 ± 0.59 in the ileum, and 0.63 ± 0.21 in the colon. During APRV without SB and high tidal volumes, it decreased to 0.19 ± 0.03 in the stomach, 0.42 ± 0.21 in the duodenum, 0.37 ± 0.10 in the jejunum, 0.3 ± 0.14 in the ileum, and 0.41 ± 0.14 in the colon (P < 0.001, respectively). During APRV without SB and low tidal volumes, the respective mucosal–submucosal blood flows decreased to 0.24 ± 0.10 (P < 0.01), 0.54 ± 0.21 (P < 0.05), 0.48 ± 0.17 (P < 0.01), 0.43 ± 0.21 (P < 0.01), and 0.50 ± 0.17 (P < 0.001) as compared to APRV with SB. Muscularis–serosal perfusion decreased during full ventilatory support with high tidal volumes in comparison with APRV with SB. Conclusion Maintaining SB during APRV was associated with better systemic and intestinal blood flows. Improvements were more pronounced in the mucosal–submucosal layer.

Controlled versus assisted mechanical ventilation.

On the basis of currently available data, it can be suggested that maintained spontaneous breathing during mechanical ventilation should not be suppressed even in patients with severe pulmonary dysfunction if no contraindications, such as increased intracranial pressure, are present. Improvements in pulmonary gas exchange, systemic blood flow, and oxygen supply to tissues, which have been observed when spontaneous breathing was allowed during ventilatory support, are reflected in the clinical improvement in the patients condition, as indicated by significantly fewer days with ventilation, earlier extubation, and shorter stays in the intensive care unit. The positive effects of spontaneous breathing have been documented only for some of the available partial ventilatory support modalities. If ventilatory modalities are limited to those whose positive effects have been documented, then partial ventilatory support can be used as a primary modality even in patients with severe pulmonary dysfunction. Whereas controlled mechanical ventilation followed by weaning with partial ventilatory support modalities has been the earlier standard in ventilation therapy, this approach should be reconsidered in view of the available data.

The effects of mechanical ventilation on the gut and abdomen.

Purpose of reviewMechanical ventilation generates an increase in airway pressure and, therefore, in intrathoracic pressure, which may decrease systemic and intraabdominal organ perfusion. Critically ill patients rarely die of hypoxia and/or hypercarbia but commonly develop a systemic inflammatory response that culminates in multiple-organ dysfunction syndrome and death. In the pathogeneses of this syndrome the gastrointestinal tract and liver have received considerable attention. Recent findingsMechanical ventilation with high positive end-expiratory pressure has been found to decrease splanchnic perfusion. Hepatic arterial buffer response is preserved and an increased hepatic arterial blood flow will compensate the decrease in portal blood flow. Despite an increased cardiac output with an acute moderate increase in arterial PCO2 during protective ventilation it cannot be expected that splanchnic and gut perfusion is improved. In the absence of a significant rise in intraabdominal pressure without impairment in cardiovascular function, splanchnic and gastrointestinal function remained unchanged during short periods of prone positioning. Spontaneous breathing during ventilator support improves systemic blood flow and gastrointestinal and splanchnic perfusion. SummaryIn critically ill patients mechanical ventilation should be adjusted to avoid conditions known to be associated with decreased gastrointestinal and splanchnic perfusion.

Incidence and prognosis of dysnatraemia in critically ill patients: analysis of a large prevalence study

The objective of this study is to assess the impact of dysnatraemia on mortality among intensive care unit (ICU) patients in a large, international cohort.

Endotoxin inhibits heat shock protein 70 (HSP70) expression in peripheral blood mononuclear cells of patients with severe sepsis

Objective: To investigate the ex vivo endotoxin-inducible heat shock protein 70 (HSP70) expression in the peripheral blood mononuclear cells (PBMC) of patients with severe sepsis in order to assess the capacity of this potentially protective response during systemic inflammation. Design: Prospective observational study in consecutive patients with severe sepsis and healthy blood donors. Setting: Surgical intensive care unit in a university hospital. Patients and participants: Eleven patients with the diagnosis of severe sepsis, one patient who had recovered from severe sepsis and 13 healthy blood donors. Interventions: None. Measurements and results: We studied the inducibility of HSP70 expression in the PBMC of patients with severe sepsis and healthy blood donors ex vivo. Human whole blood was incubated with variable lipopolysaccharide (LPS from Salmonella minnesota Re 595) concentrations (0; 0.1; 10; 100 ng/ml) for different periods of time (0.5; 2; 4; 10 h). The PBMC were separated by Ficoll density gradient and then disrupted by hypotonic lysis. HSP70 was measured by means of enzyme-linked immunosorbent assay (ELISA). We found a LPS dose- and time-dependent inhibition of ex vivo HSP70 expression in the PBMC of both patients with severe sepsis and healthy individuals. However, the levels of HSP70 expression in patients were significantly lower compared to those of healthy individuals at all LPS concentrations and incubation times. On average, HSP70 expression in the PBMC of healthy controls was 2.8 (range 1.2–3.9) times higher than in patients. HSP70 expression was inducible by thermal heat shock in the PBMC of both patients and healthy individuals. Conclusions: Endotoxin inhibits HSP70 expression in PBMC ex vivo. In vivo, the suppression of HSP70 expression induced by endotoxin and high levels of proinflammatory cytokines may contribute to the cellular dysfunction of immunocompetent cells concerning antigen presentation, phagocytosis and antibody production associated with decreased resistance to infectious insults during severe sepsis.

Cardiorespiratory Effects of Automatic Tube Compensation during Airway Pressure Release Ventilation in Patients with Acute Lung Injury

Background Spontaneous breaths during airway pressure release ventilation (APRV) have to overcome the resistance of the artificial airway. Automatic tube compensation provides ventilatory assistance by increasing airway pressure during inspiration and lowering airway pressure during expiration, thereby compensating for resistance of the artificial airway. The authors studied if APRV with automatic tube compensation reduces the inspiratory effort without compromising cardiovascular function, end-expiratory lung volume, and gas exchange in patients with acute lung injury. Methods Fourteen patients with acute lung injury were breathing spontaneously during APRV with or without automatic tube compensation in random order. Airway pressure, esophageal and abdominal pressure, and gas flow were continuously measured, and tracheal pressure was estimated. Trans-diaphragmatic pressure time product was calculated. End-expiratory lung volume was determined by nitrogen washout. The validity of the tracheal pressure calculation was investigated in seven healthy ventilated pigs. Results Automatic tube compensation during APRV increased airway pressure amplitude from 7.7 ± 1.9 to 11.3 ± 3.1 cm H2O (mean ± SD;P < 0.05) while decreasing trans-diaphragmatic pressure time product from 45 ± 27 to 27 ± 15 cm H2O · s−1 · min−1 (P < 0.05), whereas tracheal pressure am-plitude remained essentially unchanged (10.3 ± 3.5 vs. 10.1 ± 3.5 cm H2O). Minute ventilation increased from 10.4 ± 1.6 to 11.4 ± 1.5 l/min (P < 0.001), decreasing arterial carbon dioxide tension from 52 ± 9 to 47 ± 6 mmHg (P < 0.05) without affecting arterial blood oxygenation or cardiovascular function. End-expiratory lung volume increased from 2,806 ± 991 to 3,009 ± 994 ml (P < 0.05). Analysis of tracheal pressure–time curves indicated nonideal regulation of the dynamic pressure support during automatic tube compensation as provided by a standard ventilator. Conclusion In the studied patients with acute lung injury, automatic tube compensation markedly unloaded the inspiratory muscles and increased alveolar ventilation without compromis-ing cardiorespiratory function and end-expiratory lung volume.