Terlipressin as a rescue therapy for catecholamine-resistant septic shock in children

Objective To evaluate the effect of terlipressin on oxygenation, PaO₂/FIO₂, heart rate, mean arterial pressure, and mortality in children with septic shock refractory to high doses of dopamine/dobutamine and adrenaline. Design and setting A randomized, nonblind study in the pediatric intensive care unit of a university hospital. Patients and measurements We studied 58 children with septic shock and refractory hypotension despite fluid loading and high doses of catecholamines, randomly enrolled to terlipressin (TP, n = 30) or control (n = 28). TP was administered as intravenous bolus doses of 20 μg/kg every 6 h for a maximum of 96 h. Hemodynamic changes, PaO₂/FIO₂ rates, length of stay, and mortality rate in PICU were recorded prospectively. Results Mean arterial pressure and PaO₂/FIO₂ significantly increased, and heart rate significantly decreased 30 min after each TP treatment, but mortality did not differ from control (67.3% vs. 71.4%). Mean stay in the PICU was shorter in the TP group (13.4 ± 7.9 vs. 20.2 ± 9.7 days and was longer among nonsurvivors of the TP group vs. control (10.4 ± 6.9 vs. 6.2 ± 3.4 days). Blood urea nitrogen, creatinine, AST, ALT, and urine output of patients in the TP group did not change after terlipressin. Conclusions Although terlipressin infusion had no effect on mortality, it significantly increases mean arterial pressure, PaO₂/FIO₂, and survival time in nonsurvivors. Terlipressin seems to cause no adverse effect but warrants further evaluation as a rescue therapy in refractory septic shock.     

Effect of activated protein C on pulmonary blood flow and cytokine production in experimental acute lung injury

Objective In acute lung injury (ALI) activated protein C (APC) may reopen occluded lung vessels and minimize lung inflammation. We aimed at assessing the effect of APC on regional lung perfusion, aerated lung volume, cytokine production and oxygenation in experimental ALI. Design and setting Prospective, controlled study in an imaging facility. Participants Pigs tracheotomized and mechanically ventilated. Intervention Pigs were randomly given intravenously APC (n = 8) or saline (n = 8). Thirty minutes later, ALI was induced by injecting oleic acid. Measurements and results Lung perfusion and aerated lung volume measured with positron emission tomography, plasma cytokines and arterial blood gas were determined just before ALI and 110 and 290 min thereafter. Lung cytokines were measured at the end of the experiment. PaO₂ under F_IO₂ 1 was significantly lower in the APC group before lung injury (473 ± 129 vs. 578 ± 54 mmHg) and 110 min (342 ± 138 vs. 446 ± 103 mmHg) and 290 min (303 ± 171 vs. 547 ± 54 mmHg) thereafter (p < 0.05). Lung perfusion nonsignificantly tended to redistribute towards dorsal lung regions with APC. Total aerated lung volume was not different between APC and control before ALI (10.0 ± 1.5 vs. 11.0 ± 2.5 ml/kg) (p > 0.05) or thereafter. Plasma IL-6 and IL-8 at 110 min were greater with APC (p < 0.05). Conclusions In contrast to studies using other models, pretreatment with APC was associated with worsening oxygenation in the present investigation. This might be due to ventilation–perfusion mismatch, with more perfusion to dependent nonaerated areas. Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. This article is discussed in the editorial available at: .     

Effect of inspired oxygen fraction on alveolar derecruitment in acute respiratory distress syndrome

Objective High fractions of inspired oxygen (FIO₂) used in acute lung injury (ALI) may promote resorption atelectasis. The impact of derecruitment related to high FIO₂ in ALI is debated. We evaluated derecruitment with 100% vs. 60% FIO₂ at two levels of positive end-expiratory pressure (PEEP).Patients Fourteen consecutive patients with ALI were studied.Interventions Recruited volume at two PEEP levels was computed from two pressure-volume curves, recorded from PEEP and from zero end-expiratory pressure, using the sinusoidal flow modulation method. PEEP-induced recruitment was measured during prolonged expiration as the difference between the two curves at a given pressure. PaO₂/FIO₂ was also measured. PEEP was 5 ± 1 or 14 ± 3 cmH₂O and FIO₂ was 60% or 100%, yielding four combinations. We looked for differences between the beginning and end of a 30-min period with each combination.Measurement and results With low PEEP and 100% FIO₂, recruited volume decreased significantly from 68 ± 53 to 39 ± 43 ml and PaO₂/FIO₂ from 196 ± 104 to 153 ± 83 mmHg. With the three other combinations (low PEEP and 60% FIO₂ or high PEEP and 60% or 100% FIO₂) none of the parameters decreased significantly.Conclusion In mechanically ventilated patients with ALI the breathing of pure oxygen leads to derecruitment, which is prevented by high PEEP.Electronic supplementary material Supplementary material is available in the online version of this article at and is accessible for authorized users.This article is discussed in the editorial available at:     

Hemodynamics in experimental gastric juice induced aspiration pneumonitis

Objective To characterize hemodynamic changes during experimental aspiration pneumonitis, paying special attention to echocardiographic assessment. Design and setting Animal study in a university-based research laboratory. Subjects Fourteen mechanically ventilated New Zealand white rabbits Interventions We instilled 1 ml/kg human gastric juice (mean pH: 4.1 + 0.2) intratracheally. Hemodynamic and respiratory parameters were measured every hour for 4 h, associated with a transthoracic echocardiography. Measurements and results Lung injury occurred within 1 hour with a marked decrease in PaO₂/FIO₂ and an increase in plateau pressure; after this initial drop the ratio remained stable throughout the experiment. Seven rabbits experienced only a mild to moderate alteration in lung oxygenation function as defined by a PaO₂/FIO₂ ratio above 200 (group A), while the other seven developed a severe alteration with a ratio below 200 (group B). At the end of the experiment pH and cardiac output were lower in group B than in group A. Using a PaO₂/FIO₂ threshold value of 150, pH, mean arterial pressure, and cardiac output were lower in the animals with the more severe hypoxemia. Neither left nor right ventricular dysfunction occurred during the experiment, and no animal experienced circulatory failure Conclusion Experimental aspiration pneumonitis after intratracheal infusion of human gastric juice is characterized by a stable fall in PaO₂/FIO₂. Animals with the most severe lung injury experienced a lower systemic arterial pressure, cardiac output, and metabolic acidosis without circulatory failure or cardiac dysfunction.     

Effects of vertical positioning on gas exchange and lung volumes in acute respiratory distress syndrome

Objective Supine position may contribute to the loss of aerated lung volume in patients with acute respiratory distress syndrome (ARDS). We hypothesized that verticalization increases lung volume and improves gas exchange by reducing the pressure surrounding lung bases.Design and setting Prospective observational physiological study in a medical ICU.Subjects and intervention In 16 patients with ARDS we measured arterial blood gases, pressure-volume curves of the respiratory system recorded from positive-end expiratory pressure (PEEP), and changes in lung volume in supine and vertical positions (trunk elevated at 45° and legs down at 45°).Measurements and results Vertical positioning increased PaO₂ significantly from 94 ± 33 to 142 ± 49 mmHg, with an increase higher than 40% in 11 responders. The volume at 20 cmH₂O measured on the PV curve from PEEP increased using the vertical position only in responders (233 ± 146 vs. –8 ± 91 ml in nonresponders); this change was correlated to oxygenation change (ρ = 0.55). End-expiratory lung volume variation from supine to vertical and 1 h later back to supine, measured in 12 patients showed a significant increase during the 1-h upright period in responders (n = 7) but not in nonresponders (n = 5; 215 ± 220 vs. 10 ± 22 ml), suggesting a time-dependent recruitment.Conclusions Vertical positioning is a simple technique that may improve oxygenation and lung recruitment in ARDS patients.Electronic supplementary material Supplementary material is available in the online version of this article at and is accessible for authorized users.     

Hemodynamic and gas exchange responses to inhalation of nitric oxide in patients with the acute respiratory distress syndrome and in hypoxemic patients with chronic obstructive pulmonary disease

Objective: Inhalation of nitric oxide (NO) can improve oxygenation and decrease mean pulmonary artery pressure (MPAP) in patients with the acute respiratory distress syndrome (ARDS). It is not known whether inhaled NO exerts a similar effect in hypoxemic patients with chronic obstructive pulmonary disease (COPD). Design: Prospective clinical study. Setting: General intensive care unit in Sabadell, Spain. Patients: Nine mechanically ventilated COPD patients (mean age 72±2 years; forced expiratory volume in 1 s 0.91±0.11 l) and nine ARDS patients (mean age 57±6 years; mean lung injury score 2.8±0.1) Measurements and results: We measured hemodynamic and gas exchange parameters before NO inhalation (basal 1), during inhalation of 10 ppm NO (NO-10), and 20 min after NO was discontinued (in basal 2) in the ARDS group. In the COPD group, these parameters were measured before NO inhalation (basal 1), during different doses of inhaled NO (10, 20, and 30 ppm), and 20 min after NO was discontinued (basal 2). A positive response to NO was defined as a 20% increment in basal arterial partial pressure of oxygen (PaO₂). MPAP and pulmonary vascular resistance (PVR) decreased significantly, while other hemodynamic parameters remained unchanged after NO-10 in both groups. Basal oxygenation was higher in the COPD group (PaO₂/FIO₂ (fractional inspired oxygen) 190±18 mmHg) than in the ARDS group (PaO₂/FIO₂ 98±12 mmHg), (p<0.01). After NO-10, PaO₂/FIO₂ increased (to 141±17 mmHg, p<0.01) and Qva/Qt decreased (39±3 to 34±3%, p<0.01) in the ARDS group. There were no changes in PaO₂/FIO₂ and Qva/Qt when the NO concentration was increased to 30 ppm in the COPD group. In both groups, a correlation was found between basal MPAP and basal PVR, and between the NO-induced decrease in MPAP and in PVR. The NO-induced increase in PaO₂/FIO₂ was not correlated with basal PaO₂/FIO₂. In the ARDS group, six of the nine patients (66%) responded to NO and in the COPD group, two of nine (22%) (p=0.05). Conclusions: NO inhalation had similar effects on hemodynamics but not on gas exchange in ARDS and COPD patients, and this response probably depends on the underlying disease. Received: 19 December 1995 Accepted: 28 September 1996     

Intrapulmonary percussive ventilation in tracheostomized patients: a randomized controlled trial

Objective To investigate whether the addition of intrapulmonary percussive ventilation to the usual chest physiotherapy improves gas exchange and lung mechanics in tracheostomized patients.Design and setting Randomized multicenter trial in two weaning centers in northern Italy.Patients and participants 46 tracheostomized patients (age 70 ± 7 years, 28 men, arterial blood pH 7.436 ± 0.06, PaO₂/FIO₂ 238 ± 46) weaned from mechanical ventilation.Interventions Patients were assigned to two treatment groups performing chest physiotherapy (control), or percussive ventilation (IMP2 Breas, Sweden) 10 min twice/day in addition to chest physiotherapy (intervention).Measurements and results Arterial blood gases, PaO₂/FIO₂ ratio, and maximal expiratory pressure were assessed every 5th day for 15 day. Treatment complications that showed up in 1 month of follow-up were recorded. At 15 days the intervention group had a significantly better PaO₂/FIO₂ ratio and higher maximal expiratory pressure; after follow-up this group also had a lower incidence of pneumonia.Conclusions The addition of percussive ventilation to the usual chest physiotherapy regimen in tracheostomized patients improves gas exchange and expiratory muscle performance and reduces the incidence of pneumonia.Electronic supplementary material Supplementary material is available in the online version of this article at and is accessible for authorized users.This research was supported by the Italian Ministry of University and Research and Agenzia Italiana del Farmaco.     

Improvement in oxygenation by prone position and nitric oxide in patients with acute respiratory distress syndrome

Objective: Inhaled nitric oxide (NO) and prone position improve arterial oxygenation in patients with the acute respiratory distress syndrome. This study was undertaken to assess the combined effects of NO and prone position in these patients. Design: Prospective clinical study. Setting: General intensive care service in a community teaching hospital. Patients: 14 mechanically ventilated adult patients with the acute respiratory distress syndrome (mean lung injury score 3.23 ± 0.27). Measurements and results: We measured hemodynamic and oxygenation parameters in the supine position and 2 h later in the prone position, before and during inhalation of 10 ppm NO. A positive response in oxygenation was defined as a ≥ 20 % increment in the arterial oxygen tension/fractional inspired oxygen ratio (PaO₂/FIO₂). In the prone position PaO₂/FIO₂ increased significantly (from 110 ± 55 to 161 ± 89 mmHg, p < 0.01) and venous admixture decreased (from 38 ± 12 to 30 ± 7 %, p < 0.01) compared to the supine position. Ten of the 14 patients were responders in the prone position. In the supine position, inhalation of NO improved oxygenation to a lesser extent, increasing PaO₂/FIO₂ to 134 ± 64 mmHg (p < 0.01) and decreasing venous admixture to 35 ± 12 %, (p < 0.01). Five of the 14 patients responded to NO inhalation supine and 8 of 14 responded prone (p = 0.22). The combination of NO therapy and prone positioning was additive in increasing PaO₂/FIO₂ (197 ± 92 mmHg) and decreasing venous admixture (27 ± 8 %) (p < 0.01). This combination also showed a positive oxygenation response on compared to the supine value without NO in 13 of the 14 patients (93 %). NO-induced changes in PaO₂/FIO₂ were correlated to changes in pulmonary vascular resistance only in the prone position. Conclusions: In patients with the acute respiratory distress syndrome, the combination of NO and prone position is a valuable adjunct to mechanical ventilation. Received: 15 June 1998 Final revision received: 13 October 1998 Accepted: 30 October 1998     

Remifentanil-based sedation to treat noninvasive ventilation failure: a preliminary study

Objective To assess the feasibility and safety of remifentanil-based sedation during noninvasive ventilation (NIV) in patients with NIV failure. Design and setting Prospective clinical investigation in a 16-bed intensive care unit of a university hospital in France. Patients Thirteen patients in NIV failure due to discomfort and/or refusal to continue this ventilatory support: 10 with acute respiratory failure and 3 with acute hypercapnic respiratory failure. Intervention Patients were administered methylene blue and were sedated (Ramsay scale 2–3) by a continuous perfusion of remifentanil during NIV. Cardiorespiratory and ventilatory parameters, blood gas analysis, and adverse events were prospectively recorded. Measurements and results The 13 patients received a total of 125 NIV sessions, totaling 1200 h, of NIV under remifentanil-based sedation (mean remifentanil dose 0.1 ± 0.03 μg/kg per minute). Three patients also required propofol. PaO₂/FIO₂ ratio increased from 134 ± 69 to 187 ± 43 mmHg after 1 h. In patients with acute respiratory failure respiratory rate decreased from 34 ± 12 per minute before remifentanil to 25 ± 4 per minute after 1 h. In the three patients with acute hypercapnic respiratory failure PaCO₂ decreased from 69 ± 7 to 42 ± 5 mmHg. Four patients required endotracheal intubation without aspiration pneumonia. Twelve of the 13 patients left the ICU. Conclusion This pilot study shows that remifentanil-based sedation is safe and effective in the treatment of NIV failure due to low tolerance.     

Mitigation of endotoxin-induced acute lung injury in ventilated rabbits by surfactant and inhaled nitric oxide

Objective: To evaluate the efficacy of surfactant and inhaled nitric oxide (iNO) in endotoxin-induced acute lung injury (ALI).¶Design: Prospective, randomised, controlled experimental study.¶Setting: A medical university hospital research laboratory.¶Intervention: Twenty-nine adult rabbits (2.4–3.4 kg) were given two doses of intravenous endotoxin (Escherichia coli) (0.01 mg/kg and, 12 h later, 0.1 mg/kg), and then subjected to mechanical ventilation. After 8 h these animals were allocated to four treatment groups: (1) control, (2) iNO at 20 ppm (NO), (3) surfactant at 100 mg/kg (Surf) and (4) both surfactant and iNO as in groups 2 and 3 (SNO), and ventilated for a further 6 h followed by broncho-alveolar lavage (BAL), analysis of surfactant contents in BAL fluid and histological examination of the lungs.¶Measurements and results: All the animals had developed ALI with respiratory failure 8 h after the second dose of endotoxin as evidenced by a decrease of PaO₂/FIO₂ from 520 ± 30 to 395 ± 19 mmHg and dynamic compliance (Cdyn) from 1.20 ± 0.11 to 0.73 ± 0.05 ml/cmH₂O × kg, and an increase of intrapulmonary shunting (Qs/Qt) from 7.5 ± 0.8 % to 12.9 ± 1.0 % (all measurements p < 0.01 versus baseline). In the SNO group, values for PaO₂/FIO₂, Cdyn and Qs/Qt after 6 h were 301 ± 15 mmHg, 0.67 ± 0.05 ml/cmH₂O × kg and 16.5 ± 0.8 %, compared to 224 ± 26 mmHg, 0.53 ± 0.04 ml/cmH₂O × kg and 24.1 ± 2.0 %, respectively, in the control group (all measurements p < 0.01). Both Surf and NO groups showed intermediate levels of these parameters. In both Surf and SNO groups, the minimum surface tension of BAL fluid was lower, and the content of disaturated phosphatidylcholine/total protein higher, than in the control and NO groups (p < 0.01). Histological features of lung injury were less prominent and wet/dry lung weight ratio lower in the NO, Surf and SNO groups. Decreased surfactant protein A (SP-A) and its mRNA expression were found in all endotoxin-exposed groups, but the SP-A content of the SNO group was moderately improved in comparison to the control group. Surfactant aggregate size was not affected.¶Conclusion: Early application of surfactant and iNO moderately mitigated ALI as reflected by improvement of lung mechanics, pulmonary perfusion and morphology.     

Current definitions of acute lung injury and the acute respiratory distress syndrome do not reflect their true severity and outcome

Background: Despite intensive research, there are no universally accepted clinical definitions for acute lung injury (ALI) or the acute respiratory distress syndrome (ARDS). A recent joint American-European Consensus Conference on ARDS formally defined the difference between ALI and ARDS based on the degree of oxygenation impairment. However, this definition may not reflect the true prevalence, severity and prognosis of these syndromes. Methods: During a 22-month period, 56 consecutive mechanically ventilated patients who met the American-European Consensus definition for ARDS [arterial oxygen tension/fractional inspired oxygen (PaO₂/FIO₂≤ 200 mmHg regardless of the level of positive end-expiratory pressure (PEEP), bilateral pulmonary infiltrates, and no evidence of left heart failure] were admitted into the intensive care units (ICU) of the Hospital del Pino, Las Palmas, Spain, and prospectively studied. The diagnosis of ALI and ARDS was made by a PEEP-FIO₂ trial, 24 h after patients met the Consensus inclusion criteria. Patients were classified as having ALI_{–24 h} if the PaO₂/FIO₂ was > 150 mmHg with PEEP = 5 cmH₂O, and ARDS_{–24 h} if the PaO₂ /FIO₂ was ≤ 150 mmHg with PEEP ≥ 5 cmH₂O. Results: Overall mortality was 43 % (24 of 56). However, 24 h after inclusion, PaO₂ response to PEEP 5 cmH₂O allowed the separation of our patients into two different groups: 31 patients met our ALI_{–24 h} criteria (PaO₂/FIO₂ > 150 mmHg) and their mortality was 22.6 %; 25 patients met our ARDS_{–24 h} criteria (PaO₂/FIO₂≤ 150 mmHg) and their mortality was 68 % (p = 0.0016). The differences in the respiratory severity index during the first 24 h of inclusion, PaO₂/FIO₂ ratio at baseline and at 24 h, maximum plateau airway pressure, maximum level of PEEP, and number of organ system failures during the ICU stay were statistically significant. Conclusions: Since the use of PEEP in the American-European Consensus criteria for ARDS is not mandatory, that definition does not reflect the true severity of lung damage and outcome. Our data support the need for guidelines based on a specific method of evaluating oxygenation status before the American-European Consensus definition is adopted. Received: 18 April 1999 Final revision received: 30 June 1999 Accepted: 9 July 1999     

Mechanism of acute lung injury caused by inhalation of fabric protector and the effect of surfactant replacement

Objective: To evaluate the role of surfactant in the mechanism and treatment of acute lung injury caused by inhalation of fabric protector. Design: Prospective, randomized study. Setting: University laboratory. Interventions: In vitro experiment: a porcine surfactant suspension (10 mg · ml⁻¹) was exposed to a fabric protector aerosolized with an ultrasonic nebulizer for 1 min. Minimum surface tension (γ min) was sequentially measured using pulsating bubble equipment. Animal experiment: 14 adult rats were anesthetized with pentobarbital and mechanically ventilated with pure oxygen. Then, all rats inhaled fabric protector aerosolized with the nebulizer for five breaths. Three hours after inhalation, the rats were randomly assigned to two groups: a surfactant group (n = 7), in which surfactant (100 mg · kg⁻¹) was replaced, and a control group (n = 7), in which no substance was given. Measurements and results: In vitro experiment: exposure to fabric protector aerosol increased the mean γ min of the surfactant from 1.7 to 19.2 mN · m⁻¹ (n = 5, p < 0.05). Animal experiment: the mean partial pressure of oxygen in arterial blood (PaO₂) in all rats decreased from 62.8 to 17.1 kPa at 3 h after inhalation. The PaO₂ in the surfactant group increased to 49.8 ± 11.1 (SD) kPa at 30 min after surfactant replacement (p < 0.05), while the PaO₂ in the control group remained below 20 kPa. Conclusions: Impairment of surfactant is a factor involved in the development of acute lung injury caused by inhalation of fabric protector. Surfactant replacement may be therapeutic for such injuries. Received: 14 February 1997 Accepted: 28 October 1997     

Respiratory mechanics in brain-damaged patients

Objective To assess respiratory mechanics on the 1st and 5th days of mechanical ventilation in a cohort of brain-damaged patients on positive end-expiratory pressure (PEEP) of 8 cmH₂O or zero PEEP (ZEEP).Design and setting Physiological study with randomized control trial design in a multidisciplinary intensive care unit of a university hospital.Patients and measurements Twenty-one consecutive mechanically ventilated patients with severe brain damage and no acute lung injury were randomly assigned to be ventilated with ZEEP (n = 10) or with 8 cmH₂O of PEEP (n = 11). Respiratory mechanics and arterial blood gases were assessed on days 1 and day 5 of mechanical ventilation.Results In the ZEEP group on day 1 static elastance and minimal resistance were above normal limits (18.9 ± 3.8 cmH₂O/l and 5.6 ± 2.2 cmH₂O/l per second, respectively); on day 5 static elastance and iso-CO₂ minimal resistance values were higher than on day 1 (21.2 ± 4.1 cmH₂O/l; 7.0 ± 1.9 cmH₂O/l per second, respectively). In the PEEP group these parameters did not change significantly. One of the ten patients on ZEEP developed acute lung injury. On day 5 there was a significant decrease in PaO₂/FIO₂ in both groups.Conclusions On day 1 of mechanical ventilation patients with brain damage exhibit abnormal respiratory mechanics. After 5 days of mechanical ventilation on ZEEP static elastance and minimal resistance increased significantly, perhaps reflecting “low lung volume” injury. Both could be prevented by administration of moderate levels of PEEP.This work was supported by the Thorax foundation.This article is discussed in the editorial available at:     

Acute effects of continuous rotational therapy on ventilation-perfusion inequality in lung injury

Objective: To investigate ventilation-perfusion (V_A/Q) relationships, during continuous axial rotation and in the supine position, in patients with acute lung injury (ALI) using the multiple inert gas elimination technique. Design: Prospective investigation. Setting: Eighteen-bed intensive care unit in a university hospital. Patients and interventions: Ten patients with ALI (PaO₂/FIO₂ ratio < 300 mm Hg) were mechanically ventilated in a pressure controlled mode and placed on a kinetic treatment table. Measurements and results: Distributions of V_A/Q were determined 1) during rotation (after a period of 20 min) and 2) after a resting period of 20 min in the supine position. During axial rotation, intrapulmonary shunt (19.1 ± 15 % of cardiac output) was significantly reduced in comparison with when in the supine position (23 ± 14 %, p < 0.05), areas with “low” V_A/Q were not affected by the positioning maneuver. General V_A/Q mismatch (logarithmic distribution of pulmonary blood flow) was decreased during rotation (0.87 ± 0.37) in comparison with when the patient was in the supine position (0.93 ± 0.37, p < 0.05). Arterial oxygenation was significantly improved during continuous rotation (PaO₂/FIO₂ = 217 ± 137 mm Hg) as compared with in the supine position (PaO₂/FIO₂ = 174 ± 82 mm Hg, p < 0.05). The positive response of the continuous rotation on arterial oxygenation was only demonstrated in patients with a Murray Score of 2.5 or less, indicating a “mild to moderate” lung injury, while in patients presenting with progressive ARDS (Murray Score > 2.5), the acute positive response was limited. Conclusions: Continuous axial rotation might be a method for an acute reduction of V_A/Q mismatch in patients with mild to moderate ALI, but this technique is not effective in late or progressive ARDS. Further studies including a large data collection are needed. Received: 19 June 1997 Accepted: 6 November 1997     

Heat and moisture exchangers and heated humidifiers in acute lung injury/acute respiratory distress syndrome patients. Effects on respiratory mechanics and gas exchange

Objective To compare, in acute lung injury/acute respiratory distress syndrome (ALI/ARDS) patients, the short-term effects of heat and moisture exchangers (HME) and heated humidifiers (HH) on gas exchange, and also on respiratory system mechanics when isocapnic conditions are met. Design Prospective open clinical study. Setting Intensive Care Service. Patients Seventeen invasively ventilated ALI/ARDS patients. Intervention The study was performed in three phases: (1) determinations were made during basal ventilatory settings with HME; (2) basal ventilatory settings were maintained and HME was replaced by an HH; (3) using the same HH, tidal volume (Vt) was decreased until basal PaCO₂ levels were reached. FiO₂, respiratory rate and PEEP were kept unchanged. Measurements and results Respiratory mechanics, Vd_phys, gas exchange and hemodynamic parameters were obtained at each phase. By using HH instead of HME and without changing Vt, PaCO₂ decreased from 46 ± 9 to 40 ± 8 mmHg (p < 0.001) and Vd_phys decreased from 352 ± 63 to 310 ± 74 ml (p < 0.001). Comparing the first phase with the third, Vt decreased from 521 ± 106 to 440 ± 118 ml (p < 0.001) without significant changes in PaCO₂, Vd/Vt decreased from 0.69 ± 0.11 to 0.62 ± 0.12 (p < 0.001), plateau airway pressure decreased from 25 ± 6 to 21 ± 6 cmH₂O (p < 0.001) and respiratory system compliance improved from 35 ± 12 to 42 ± 15 ml/cmH₂O (p < 0.001). PaO₂ remained unchanged in the three phases. Conclusions Reducing dead space with the use of HH decreases PaCO₂ and more importantly, if isocapnic conditions are maintained by reducing Vt, this strategy improves respiratory system compliance and reduces plateau airway pressure     

Assessing pulmonary permeability by transpulmonary thermodilution allows differentiation of hydrostatic pulmonary edema from ALI/ARDS

Objective To test whether assessing pulmonary permeability by transpulmonary thermodilution enables to differentiate increased permeability pulmonary edema (ALI/ARDS) from hydrostatic pulmonary edema. Design Retrospective review of cases. Setting A 24-bed medical intensive care unit of a university hospital. Patients Forty-eight critically ill patients ventilated for acute respiratory failure with bilateral infiltrates on chest radiograph, a PaO₂/FiO₂ ratio < 300 mmHg and extravascular lung water indexed for body weight ≥ 12 ml/kg. Intervention We assessed pulmonary permeability by two indexes obtained from transpulmonary thermodilution: extravascular lung water/pulmonary blood volume (PVPI) and the ratio of extravascular lung water index over global end-diastolic volume index. The cause of pulmonary edema was determined a posteriori by three experts, taking into account medical history, clinical features, echocardiographic left ventricular function, chest radiography findings, B-type natriuretic peptide serum concentration and the time-course of these findings with therapy. Experts were blind for pulmonary permeability indexes and for global end-diastolic volume. Measurements and results ALI/ARDS was diagnosed in 36 cases. The PVPI was 4.7 ± 1.8 and 2.1 ± 0.5 in patients with ALI/ARDS and hydrostatic pulmonary edema, respectively (p < 0.05). The extravascular lung water index/global end-diastolic volume index ratio was 3.0 × 10⁻² ± 1.2 × 10⁻² and 1.4 × 10⁻² ± 0.4 × 10⁻² in patients with ALI/ARDS and with hydrostatic pulmonary edema, respectively (p < 0.05). A PVPI ≥ 3 and an extravascular lung water index/global end-diastolic index ratio ≥ 1.8 × 10⁻² allowed the diagnosis of ALI/ARDS with a sensitivity of 85% and specificity of 100%. Conclusion These results suggest that indexes of pulmonary permeability provided by transpulmonary thermodilution may be useful for determining the mechanism of pulmonary edema in the critically ill. This article is discussed in the editorial available at:     

Reduction in alveolar macrophages attenuates acute ventilator induced lung injury in rats

Objective Alveolar macrophages are the sentinel cell for activation of the inflammatory cascade when the lung is exposed to noxious stimuli. We investigated the role of macrophages in mechanical lung injury by comparing the effect of high-volume mechanical ventilation with or without prior depletion of macrophages. Design and setting Randomized sham-controlled animal study in anesthetized rats. Methods Lung injury was induced by 15 min of mechanical ventilation (intermittent positive pressure ventilation) using high peak pressures and zero end-expiratory pressure. The mean tidal volume was 40 ± 0.7 ml/kg. One group of animals was killed immediately after this period of volutrauma (HV), while in a second group normoventilation was continued for 2 h at a tidal volume less than 10 ml/kg (HV-LV). One-half of the animals were depleted of alveolar macrophages by pretreatment with intratracheal liposomal clodronate (CL₂MDP). Measurements Arterial blood gas, blood pressure. After kill: lung static pressure volume curves, bronchoalveolar fluid concentration for protein, macrophage inflammatory protein 2, tumor necrosis factor α, and wet/dry lung weight ratio (W/D). Results During HV and HV+LV oxygenation, lung compliance, and alveolar stability were better preserved in animals pretreated with CL₂MDP. In both groups W/D ratio was significantly greater in ventilated than in nonventilated animals (4.5 ± 0.6), but the increase in W/D was significantly less in CL₂MDP treated HV and HV-LV groups (6.1 ± 0.4, 6.6 ± 0.6) than in the similarly ventilated nontreated groups (8.7 ± 0.2 and 9.2 ± 0.5). Conclusions Alveolar macrophages participate in the early phase of ventilator-induced lung injury. This research was performed at the University of South Alabama, Mobile, AL.     

Intravenous tezosentan improves gas exchange and hemodynamics in acute lung injury secondary to meconium aspiration

Objective Meconium aspiration induces acute lung injury (ALI) and subsequent pulmonary arterial hypertension (PAH) which may lead to right ventricular failure. Increase of endothelin-1, thromboxane-A, and phosphodiesterases are discussed molecular mechanisms. We investigated the intrapulmonary and hemodynamic effects of the intravenous dual endothelin A and B receptor blocker tezosentan and inhalational iloprost in a model of ALI due to meconium aspiration. Design Animal study. Setting University-affiliated research laboratory. Subjects White farm pigs. Interventions Acute lung injury was induced in 24 pigs by instillation of meconium. Animals were randomly assigned to four groups to receive either intravenous tezosentan, inhalational iloprost, or combined tezosentan and iloprost, or to serve as controls. Measurements and results After meconium aspiration-induced lung injury each treatment increased oxyhemoglobin saturations (TEZO: 88 ± 6% (p = 0.02), ILO: 85 ± 13% (p = 0.05), TEZO-ILO: 89 ± 6% (p = 0.02), control: 70 ± 18%). TEZO but not ILO significantly decreased pulmonary arterial pressure and pulmonary vascular resistance (both p < 0.01). ILO alone decreased intrapulmonary shunt blood flow (p < 0.01). Compared with control, TEZO-ILO yielded the highest arterial partial pressure of oxygen (70 ± 6 torr vs.49 ± 9 torr, p = 0.04), although it decreased arterial blood pressure (change from 71 ± 13 mmHg to 62 ± 12 mmHg vs.85 ± 14 mmHg to 80  ± 11 mmHg (p = 0.01). Conclusions Intravenous TEZO improves pulmonary gas exchange and hemodynamics in experimental acute lung injury secondary to meconium aspiration. Inhaled ILO improves gas exchange only, thereby reducing intrapulmonary shunt blood flow. Combination of TEZO and ILO marginally improves pulmonary gas exchange at the disadvantage of pulmonary selectivity. Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Long chain versus medium chain lipids in patients with ARDS: effects on pulmonary haemodynamics and gas exchange

Objective: To compare pulmonary haemodynamic and gas exchange alterations in septic patients with ARDS receiving long-chain triglycerides (LCT) versus medium-chain triglycerides (MCT). Design: Prospective, randomised, clinical study. Setting: Surgical ICU patients in a University Hospital. Patients: Twenty-one septic patients with ARDS were randomly assigned to receive 50 % of their non-protein caloric requirements as either 20 % LCT (group 1, n = 10) or 20 % 1 : 1 mixture of LCT/MCT (group 2, n = 11). Intervention: Intravenous infusion of LCT and LCT/MCT combinations at a rate of 12 g · h^{− 1}. Measurements and results: The LCT infusion was associated with an increase of pulmonary venous admixture (Qva/Qt) from 24 % ± 5 % to 37 % ± 6 %, an increase of mean pulmonary artery pressure (MPAP) from 25 ± 5 to 33 ± 4 mmHg and decrease of PaO₂/FIO₂ from 240 ± 30 to 180 ± 35. LCT/MCT administration was only associated with an elevation of oxygen consumption (VO₂) from 329 ± 14 to 396 ± 12 ml/min. During lipid infusion group 1 patients presented higher Qva/Qt (37 % ± 6 % vs 25 % ± 4 %), MPAP (33 ± 4 vs 27 ± 3 mmHg) and VO₂ (359 ± 11 vs 396 ± 12 ml/min) and lower PaO₂/FIO₂ (180 ± 35 vs 235 ± 30) values compared to group 2. Conclusion: In conclusion, we have shown that, in septic patients with respiratory failure, LCT administration was associated with more significant changes of Qva/Qt, MPAP and PaO₂/FIO₂ compared to infusion of an LCT/MCT 1 : 1 emulsion. Clinically, these transient alterations might cause serious problems in patients with marginal arterial oxygenation and cardio-respiratory impairment. Received: 23 July 1997 Accepted: 15 May 1998     

Does gas exchange response to prone position predict mortality in hypoxemic acute respiratory failure?

Objective To determine whether gas exchange response to a first prone position session can predict patient outcome in hypoxemic acute respiratory failure.Methods Data from a previous multicenter randomized controlled trial were retrospectively analyzed for relationship between PaO₂/FIO₂ ratio and PaCO₂ changes during the first 8-h prone position session to day 28 mortality rate; 370 prone position sessions were analyzed. Arterial blood gas was measured in supine position before proning and in prone position at the end of the session. Gas exchange improvement was defined as increase in the PaO₂/FIO₂ ratio of more than 20% (PaO₂R) or decrease in PaCO₂ of more than 1 mmHg (PaCO₂R).Main results The 28-day mortality rate was 26.5% in PaO₂R–PaCO₂R, 31.7% in PaO₂R–PaCO₂NR, 38.9% in PaO₂NR–PaCO₂R, and 43% in PaO₂NR–PaCO₂NR (log-rank 14.02, p = 0.003). In a Cox proportional hazards model the gas exchange response was a significant predictor to patient outcome with a 82.5% increase in risk of death in the case of PaO₂NR–PaCO₂R or PaO₂NR–PaCO₂NR, relative to the gas exchange improvement response (odds ratio 1.825). However, after adjusting for the difference in oxygenation between day 2 and day 1 the gas exchange response does no longer reach significance.Conclusion In patients with hypoxemic acute respiratory failure initial improvement in gas exchange in the first PP session was associated with a better outcome, but this association disappeared when the change in oxygenation from day 1 to day 2 was taken into account, suggesting that underlying illness was the most important predictor of mortality in this patient population.This work was supported by Hospices Civils de Lyon, Lyon, France, and Ministère de la Santé, Programme Hospitalier de Recherche Clinique, Paris, France