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     

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.     

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     

Additive effect on gas exchange of inhaled nitric oxide and intravenous almitrine bismesylate in the adult respiratory distress syndrome

Objective To assess the additive effect of inhaled nitric oxide (NO) and intravenous almitrine bismesylate (ALM) on gas exchange.Design Prospective self-controlled study.Setting 3 medico-surgical intensive care units.Patients 17 patients with severe hypoxemia (PaO₂/FIO₂ ratio: 88±30mmHg, venous admixture: 47±7%) and elevated mean pulmonary artery pressure (MPAP: 30±5mmHg) due to adult respiratory distress syndrome (ARDS).Interventions 5 conditions were studied: 1) baseline, 2) 5 to 10ppm of NO during 30min, 3) discontinuation of NO during 30min, 4) ALM infusion (0.5mg/kg) during 30min, 5) ALM infusion (0.5mg/kg) during 30min in combination with 5 to 10ppm of NO.Measurement and results The PaO₂/FIO₂ ratio rose from 88±30 to 98±37mmHg (NS) with NO alone, and from 92±25 to 130±56mmHg (p<0.01) with NO+ALM (p<0.05 vs NO alone). Seven patients were considered as NO-responders (rise in PaO₂/FIO₂ ratio of 10mmHg or more with NO); in this subgroup the PaO₂/FIO₂ ratio rose from 87±30 to 128±39mmHg (p<0.05) with NO alone, and from 93±20 to 169±51mmHg (p<0.01) with NO+ALM (p<0.05 versus NO alone). MPAP decreased from 30±5 to 26±5mmHg (p<0.01) with NO alone, increased slightly from 28±5 to 31±5mmHg (NS) with ALM alone and decreased to 27±5mmHg (p<0.05) with NO+ALM.Conclusions NO+ALM had additive effects on gas exchange while decreasing MPAP in patients with ARDS. The effects of NO alone were small and non significant, except in a subgroup of 7 patients in whom the combination of both therapies had the more pronounced results.     

Gas exchange and pulmonary haemodynamic responses to fat emulsions in acute respiratory distress syndrome

Objective: To investigate the gas exchange and pulmonary haemodynamic responses to two different intravenous fat emulsions in patients with acute respiratory distress syndrome (ARDS). Design: Prospective, randomized, double-blind, placebo-controlled study. Setting: Intensive care unit in a university-affiliated hospital. Patients: 21 patients with ARDS [mean age, 57 ± 3 (SEM) years; Acute Physiology and Chronic Health Evaluation II, 20 ± 3; Murray's score, 2.85 ± 0.12] consecutively admitted. Interventions: Patients were assigned to three groups (n = 7 each): group A (LCT) received long-chain triglycerides (20 % LCT), group B (MCT/LCT), medium-chain triglycerides/long-chain triglycerides (20 % MCT/LCT: 50/50) and group C placebo (0.9 % sodium chloride, NaCl). The infusion was always given at the rate of 2 mg/kg min over a total period of 12 h, with a volume infusion of 500 ml in each group. Measurements: Data were collected before, immediately after and 12 h after infusion ceased. Pulmonary and systemic haemodynamic and gas exchange variables were measured at each time point. Serum triglyceride cholesterol, and non-esterified fatty acids levels were measured. Results: During LCT infusion, cardiac output, oxygen consumption and oxygen delivery increased (all p < 0.05), whereas pulmonary haemodynamics, arterial oxygen tension, mixed venous partial pressure of oxygen and venous admixture ratio remained essentially unaltered. No changes were observed following MCT/LCT infusion. Conclusions: The administration of LCT emulsion given at a slow rate did not alter arterial oxygenation because of the beneficial effect of a high cardiac output, hence offsetting the detrimental effect of increased O₂ consumption. Received: 1 December 1997 Accepted: 3 June 1998     

Venous admixture (Qva/Q) and true shunt (Qs/Qt) in ARF patients: Effects of PEEP at constant FIO2

Venous admixture (Qva/Q) in ARF patients is due to both true right to left shunt (Qs/Qt: perfusion of truly unventilated areas) and to maldistribution ((Qva-Qs)/Qt: effects of unevenness of ventilation/perfusion ratio). Using the retention rate of sulphur hexafluoride we determined the effects of PEEP on Qs/Qt and (Qva-Qs)/Qt at a constant F_IO₂ for each patient (0.57±0.19 SD, range 0.4–0.95). Eleven patients with ARF (treated either by CPPV or CPAP) were studied on 16 occasions. Each measurement was repeated at two levels of PEEP, 5 cm H₂O below and 5 cm H₂O above the patient's clinically determined PEEP level. The increase in PEEP resulted in: — a decrease in Qva/Q (from 0.37±0.13 to 0.27±0.12,p<0.01); — a parallel decrease in Qs/Qt (from 0.29±0.16 to 0.22±0.14,p<0.01); there was a positive correlation between Qva/Q and Qs/Qt changes (r=0.53,p<0.05). No significant variation was demonstrated in (Qva-Qs)/Qt (from 0.074±0.045 to 0.054±0.048). On the other hand there was a negative correlation between the fraction of Qva/Q due to the maldistribution and F_IO₂: (Qva-Qs)/Qva=0.75–0.86 F_IO₂ (r=0.74,p<0.01). We conclude that: PEEP decreased Qva/Q mainly through changes in Qs/Qt but did not have a definite effect on (Qva-Qs)/Qt. Maldistribution was responsible for a significant portion of Qva/Q in those ARF patients tolerating a relatively low F_IO₂ (0.4–0.6).     

Fat emulsions containing medium chain triglycerides in patients with sepsis syndrome: Effects on pulmonary hemodynamics and gas exchange

Fat emulsions containing medium chain triglycerides (MCT) have recently been introduced into clinical practice as a component of total parenteral nutrition. Since several authors reported increased pulmonary artery pressure and impaired gas exchange during intravenous (i.v.) fat use, in particular in septic patients, we studied the pulmonary hemodynamic and gas exchange effects of i.v. fat containg MCT and long chain triglycerides (LCT) in patients with sepsis syndrome. As the effects of fat emulsions have been attributed to increased formation of prostanoids, the production of thromboxane A₂ and prostacyclin was investigated by the determination of urinary thromboxane B₂ and 6-keto-prostaglandin F₂, respectively. The i.v. fat use did not induce any alterations in pulmonary hemodynamics and gas exchange, the distribution of ventilation and perfusion nor urinary probably content. We conclude that fat emulsions containing MCT induce little alterations in pulmonary hemodynamics and gas exchange. This result is probably due to reduced prostaglandin formation because fat emulsions containing MCT provide less prostaglandin precursors than pure LCT emulsions.     

Parenteral nutrition in the critically ill: Use of a medium chain triglyceride emulsion

Objectives The study investigated the use of an intravenous lipid emulsion containing medium chain tryglycerides (MCTs) in critically ill patients, and compared the effects with those of a conventional long chain triglyceride (LCT) preparation.Design Patients received a parenteral nutrition regime including either 500 ml 20% Lipofundin MCT/LCT (1/1) per day, or 500 ml 20% Lipofundin S (LCT) infused over 8 h each evening.Setting The patients were receiving treatment, including assisted ventilation, in the Intensive Care Unit of a large teaching hospital. All patients on this unit for at least 3 days and who were likely to receive parenteral nutrition for at least a week were considered, unless they had severe renal or liver disease, or trauma/major surgery in the previous 3 days. Because ICU patients are a heterogenous group, subjects were randomised within clinical groups to receive either lipid. There were 24 patients entered into the study and the data on 20 matched patients is reported.Measurements and results Blood specimens were collected pre-TPN, daily at 0800 and after 5 h lipid infusion on days 1 and 6. Urine collections (24 h) were also performed. There were no apparent adverse effects due to the new MCT/LCT emulsion. Plasma ketone and glycerol concentrations were higher during MCT/LCT infusion, but 8 h post infusion plasma levels of ketones, triglycerides, non-esterified fatty acids and glucose were similar. Urinary carnitine excretion was high in all patients and was not significantly different between the groups. Nitrogen balance was less negative in patients receiving MCT/LCT on days 6 and 9.Conclusion MCTs are rapidly hydrolysed and oxidised to fatty acids and ketones which can be readily utilised. This study indicates that intravenous lipid emulsion containing MCT are safe in critically ill patients and may have advantages over LCT. The number and range of patients studied was, however, small and larger studies are needed.     

High survival rate in 122 ARDS patients managed according to a clinical algorithm including extracorporeal membrane oxygenation

Objective: We investigated whether a treatment according to a clinical algorithm could improve the low survival rates in acute respiratory distress syndrome (ARDS). Design: Uncontrolled prospective trial. Setting: One university hospital intensive care department. Patients and participants: 122 patients with ARDS, consecutively admitted to the ICU. Interventions: ARDS was treated according to a criteria-defined clinical algorithm. The algorithm distinguished two main treatment groups: The AT-sine-ECMO (advanced treatment without extracorporeal membrane oxygenation) group (n = 73) received a treatment consisting of a set of advanced non-invasive treatment options, the ECMO treatment group (n = 49) received additional extracorporeal membrane oxygenation (ECMO) using heparin-coated systems. Measurements and results: The groups differed in both APACHE II (16 ± 5 vs 18 ± 5 points, p = 0.01) and Murray scores (3.2 ± 0.3 vs 3.4 ± 0.3 points, p = 0.0001), the duration of mechanical ventilation prior to admission (10 ± 9 vs 13 ± 9 days, p = 0.0151), and length of ICU stay in Berlin (31 ± 17 vs 50 ± 36 days, p = 0.0016). Initial PaO₂/FIO₂ was 86 ± 27 mm Hg in AT-sine-ECMO patients that improved to 165 ± 107 mm Hg on ICU day 1, while ECMO patients showed an initial PaO₂/FIO₂ of 67 ± 28 mm Hg and improvement to 160 ± 102 mm Hg was not reached until ICU day 13. Q˙_S/Q˙_T was significantly higher in the ECMO-treated group and exceeded 50 % during the first 14 ICU days. The overall survival rate in our 122 ARDS patients was 75 %. Survival rates were 89 % in the AT-sine ECMO group and 55 % in the ECMO treatment group (p = 0.0000). Conclusions: We conclude that patients with ARDS can be successfully treated with the clinical algorithm and high survival rates can be achieved. Received: 9 April 1997 Accepted: 13 May 1997     

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:     

Short-term effects of prone position in chronic obstructive pulmonary disease patients with severe acute hypoxemic and hypercapnic respiratory failure

Objective To assess the short-term effects of prone positioning (PP) in chronic obstructive pulmonary disease (COPD) patients with severe hypoxemic and hypercapnic respiratory failure requiring invasive mechanical ventilation.Design and setting Prospective observational study in the general intensive care unit of a university-affiliated hospital.Patients 11 consecutive COPD patients with persistent hypoxemia (PaO₂/FIO₂ 200 mmHg with FIO₂ 0.6) and hypercapnia requiring invasive mechanical ventilation. Patients with adult respiratory distress syndrome or left ventricular failure were excluded. Mean age was 73±11 years, mean weight 86±31 kg, mean SAPS II 53±10, and ICU mortality 36%.Interventions Patients were turned every 6 h.Measurements and results A response to PP (20% or greater PaO₂/FIO₂ increase) was noted in 9 (83%) patients. Blood gases were measured in the PP and supine (SP) positions 3 h after each turn, for 36 h, yielding six measurement sets (SP1, PP1, SP2, PP2, SP3, and PP3). PaO₂/FIO₂ was significantly better in PP: 190±26 vs. 113±9 mmHg for PP1/SP1, 175±22 vs. 135±16 mmHg for PP2/SP2, and 199±24 vs. 151±13 mmHg for PP3/SP3. After PP1 PaO₂/FIO₂ remained significantly improved, and the PaO₂/FIO₂ improvement from SP1 to SP2 was linearly related to PaO₂/FIO₂ during PP1 (r=0.8). The tracheal aspirate volume improved significantly from SP1 to PP1. PaCO₂ was not significantly affected by position.Conclusions PP was effective in treating severe hypoxemia in COPD patients. The first turn in PP was associated with increased tracheal aspirate.This article refers to the editorial     

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     

Effect of medium- and long-chain triglyceride infusion on lipoprotein and hepatic lipase in healthy subjects

Plasma lipolytic activity and hydrolysis of intravenous fat were studied in six healthy subjects during infusion of a long-chain triglyceride (LCT) fat emulsion (Intralipid 20%) or of a medium-chain triglyceride (MCT)/LCT emulsion (Lipofundin MCT 20%). The fat emulsions were infused continuously at a rate of 0.17 g triglyceride kg-1 body weight (BW)h-1 for 6 h in random order at 7-day intervals. A continuous infusion of glucose (0.18 g kg-1 BW h-1) was administered for a period of 7 h and was started 1 h before the lipid infusion. Infusions of both types of fat increased plasma triglyceride (TG), free fatty acid (FFA) and lipoprotein lipase (LPL) levels and steady-state values were present during the 3rd to 5th h of infusion. MCT/LCT infusion resulted in higher plasma levels at steady-state of TG (3.63 +/- 0.45 [SEM] vs 2.73 +/- 0.45 mmol l-1; P less than 0.05), FFA (1.05 +/- 0.08 vs 0.54 +/- 0.04 mmol l-1; P less than 0.01) and LPL (4.6 +/- 0.6 vs 2.6 +/- 0.5 mU ml-1; P less than 0.05) in comparison with LCT administration. There was a positive correlation between plasma LPL activity and TG concentration (r = 0.77; P less than 0.001) when data for the two infusions were combined. Although the same amount of fat was infused on a weight basis, the molar infusion rate was 40% higher with MCT/LCT than with LCT infusion, due to differences in molecular weights (634 vs 885 Da).(ABSTRACT TRUNCATED AT 250 WORDS)     

Predictors of respiratory function deterioration after transfer of critically ill patients

Objectives: Critically ill patients are often transferred due to the growing number of diagnostic procedures required to be performed outside the intensive care unit. These transfers have proved to be very critical. The aim of this study was to evaluate predictors for the deterioration of respiratory function in critically ill patients after transfer. Design: Prospective, clinical, observational study. Setting: 1800-bed university teaching hospital. Subjects: 98 mechanically ventilated patients were investigated during transfer. Measurement and main results: Before transfer, all patients were classified according to the Acute Physiology and Chronic Health Evaluation (APACHE) II score and the Therapeutic Intervention Scoring System (TISS). Haemodynamics and arterial blood gases were measured at 11 different times. Arterial oxgen tension (PaO₂), fractional inspired oxygen (FIO₂), PaO₂/FIO₂ ratio, lowest PaO₂/FIO₂ ratio, minimal PaO₂ and maximal FIO₂, APACHE II score, TISS before transfer, age and duration of transfer were analysed as potential predictors for deterioration of respiratory function after transfer. Variables were analysed using Classification and Regression Trees and Clustering by Response. In 54 transports (55 %) there was a decrease in the PaO₂/FIO₂ ratio, and a decrease of more than 20 % from baseline was noted in 23 of the transferred patients (24 %). Age > 43 years and FIO₂ > 0.5 were identified as predictors for respiratory deterioration. Conclusions: Our predictors were able to indicate deterioration after transfer correctly in 20 of 22 patients (91 %), combined with a false-positive rate in 17 of 49 (35 %). Received: 4 December 1997 Accepted: 14 August 1998     

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.     

Noninvasive ventilation for the treatment of acute respiratory failure in patients with hematologic malignancies: a pilot study

Objective: To evaluate treatment with noninvasive ventilation (NIV) by nasal mask as an alternative to endotracheal intubation and conventional mechanical ventilation in patients with hematologic malignancies complicated by acute respiratory failure to decrease the risk of hemorrhagic complications and increase clinical tolerance. Design: Prospective clinical study. Setting: Hematologic and general intensive care unit (ICU), University of Rome “La Sapienza”. Patients: 16 consecutive patients with acute respiratory failure complicating hematologic malignancies. Interventions: NIV was delivered via nasal mask by means of a BiPAP ventilator (Respironics, USA); we evaluated the effects on blood gases, respiratory rate, and hemodynamics along with tolerance, complications, and outcome. Measurements and results: 15 of the 16 patients showed a significant improvement in blood gases and respiratory rate within the first 24 h of treatment. Arterial oxygen tension (PaO₂), PaO₂/FIO₂ (fractional inspired oxygen) ratio, and arterial oxygen saturation significantly improved after 1 h of treatment (43 ± 10 vs 88 ± 37 mmHg; 87 ± 22 vs 175 ± 64; 81 ± 9 vs 95 ± 4 %, respectively) and continued to improve in the following 24 h (p < 0.01). Five patients died in the ICU following complications independent of the respiratory failure, while 11 were discharged from the ICU in stable condition after a mean stay of 4.3 ± 2.4 days and were discharged in good condition from the hospital. Conclusions: NIV by nasal mask proved to be feasible and appropriate for the treatment of respiratory failure in hematologic patients who were at high risk of intubation – related complications. Received: 21 April 1998 Accepted: 18 September 1998     

Validation of a new closed circuit indirect calorimetry method compared with the open Douglas bag method

New equipment designed for the routine measurement of oxygen uptake (VO₂) using a closed circuit method has been validated by comparing it with a standard Douglas bag method. The equipment (The Caloric Measurement Unit, CMU) has been tested in 10 critically ill patients during mechanical ventilation (MV) and in 10 spontaneously breathing healthy subjects. Determinations of VO₂ and of the resting energy expenditure (REE) were measured in duplicate with the standard method and once with the CMU. Six additional patients receiving MV were studied with the CMU to evaluate the reproducibility and the effect of FIO₂=1 vs FIO₂=0.43 on VO₂ measurements. Considering the whole group of 10 patients and 10 subjects, the mean difference of VO₂ between both methods was-2±21 ml/min (95% confidence interval,-11.8 to 7.8 ml/min, p=0.6) standard deviation. Both methods had a similar reproducibility and the mean difference of VO₂ measured at the two different FIO₂ with the CMU was-3.2±11 ml/min (95% confidence interval,-14.7 to 8.4 ml/min, p=0.5). No statistically significant difference was found between derived REE values obtained from either method. These data show a good correlation between the two methods suggesting that CMU may be used in place of the standard method with the same accuracy in measurement of VO₂ even at FIO₂=1.     

Neutrophil chemotaxis and receptor expression in clinical septic shock

Objective To examine the hypothesis that neutrophil chemotaxis to interleukin-8 (IL-8) is reduced in septic shock. Surface expression of neutrophil CXC chemokine receptors and the adhesion molecule CD11b were also examined and associations between disease severity, gas exchange and receptor expression were studied.Design Prospective cohort clinical study.Setting Intensive care unit in a tertiary referral teaching hospital.Patients Patients with septic shock (n=15) and healthy controls (n=8) were studied.Measurements and results Daily (for 5 consecutive days) flow cytometric measurements of chemokine and integrin surface expression. In vitro neutrophil chemotaxis to IL-8 was also compared between patients with sepsis and healthy controls. CXCR2 expression significantly fell, CD11b expression increased and CXCR1 expression was unchanged throughout the study in the septic group compared with healthy controls. CD11b positively correlated with increasing APACHE II scores (p<0.0001) and worsening PaO₂/FIO₂ ratios (p<0.0001). CXCR2 expression negatively correlated with both APACHE II scores (p=0.016) and PaO₂/FIO₂ ratios (p=0.01). There was no correlation between CXCR1 expression and either APACHE II score or PaO₂/FIO₂ ratios. Chemotaxis to IL-8 was reduced in patients with sepsis compared with healthy volunteers.Conclusions Surface expression of the chemokine receptor CXCR2 and the -integrin CD11b, but not CXCR1, were reduced on neutrophils isolated from patients with septic shock compared with healthy controls. Chemotaxis to IL-8 was also reduced in neutrophils from septic patients compared with healthy controls. The changes in receptor expression correlated with measures of disease severity.     

Incidence and prognostic value of right ventricular failure in acute respiratory distress syndrome

Objective  To analyse the incidence and the impact on outcome of right ventricular failure (RVF) in patients with acute respiratory distress syndrome (ARDS). Patients and methods  A total of 145 ARDS patients included in the previously published French Pulmonary Artery Catheter (PAC) study were randomly assigned to receive a PAC. All patients were ventilated according to a strategy aimed at limiting plateau pressure. The RVF was defined by the concomitant presence of: (1) a mean pulmonary artery pressure (MPAP) > 25 mmHg, (2) a central venous pressure (CVP) higher than pulmonary artery occlusion pressure (PAOP) and (3) a stroke volume index < 30 mL m⁻². Results  Right ventricular failure was present in 9.6% of patients. Mortality was 68% at day-90 with no difference between patients with RVF (RVF+) and without RVF (71 vs. 67%, respectively). SAPS II, PaO₂/FiO₂ and PaCO₂ were similar in both groups. Tidal volume and I/E ratio were significantly higher in RVF+ (9.7 ± 2.8 vs. 8.6 ± 1.8 ml m⁻² and 0.7 ± 0.5 vs. 0.5 ± 0.2). Plateau pressure tended to be higher in RVF+ (28 ± 6 vs. 25 ± 6 cmH₂O, NS). In multivariate analysis, PaO₂/FiO₂, mean arterial pressure, arterial pH, SvO₂, MPAP and presence of CVP > PAOP, but not RVF, were independently associated with day-90 mortality. Conclusion  In this group of patients investigated early in the course of ARDS and ventilated according to a strategy aimed at limiting plateau pressure, the presence of RVF was about 10%. Unlike MPAP and the presence of CVP > PAOP, RVF at this early stage did not appear as an independent factor of mortality. This article is discussed in the editorial available at: doi:.     

Effects of high-frequency oscillatory ventilation on circulation in neonates with pulmonary interstitial emphysema or RDS

Objective: Mechanical ventilation may impair cardiovascular function if the transpulmonary pressure rises. Studies on the effects of high-frequency oscillatory ventilation (HFOV) on cardiovascular functions have yielded conflicting results. This study was done to compare alterations in left ventricular output and blood flow velocities in the anterior cerebral artery, internal carotid artery, and celiac artery using a Doppler ultrasound divice before and 2 h after initiating HFOV in neonates with respiratory distress syndrome (RDS) or pulmonary interstitial emphysema (PIE). Design: Prospective clinical study. Setting: Neonatal intensive care unit in a perinatal center. Patients: 18 critically ill infants (postnatal age 47 ± 12 h; mean ± SD) were studied before and during HFOV (piston oscillator). Indications for HFOV were severe respiratory failure due to PIE (n = 10) and severe surfactant deficiency (RDS, n = 8). In the RDS group, gestational age was 27 ± 6 weeks (range 26–31 weeks) and birthweight 1620 ± 380 g (range 850–1970 g). In the PIE group, gestational age was 28 ± 2 weeks (range 26–36 weeks) and birthweight 1740 ± 470 g (range 890–2760 g). Measurements and main results: During HFOV, mean airway pressure was maintained at the same level as during intermittent mandatory ventilation in both groups (RDS, 12 ± 2 cmH₂O; PIE, 10 ± 2 cmH₂O). Compared to intermittent mandatory ventilation, several of the 12 parameters studied changed significantly (p < 0.004) during HFOV. In the RDS group, the partial pressure of oxygen in arterial blood/fractional inspired oxygen (PaO₂/FIO₂) ratio increased from 56 ± 9 to 86 ± 7 and partial pressure of carbon dioxide in arterial blood (PaCO₂) decreased from 49 ± 4 to 35 ± 3 mmHg. In the PIE group, PaO₂/FIO₂ ratio increased from 63 ± 8 to 72 ± 7 and PaCO₂ decreased from 63 ± 7 to 40 ± 5 mmHg. In the PIE group, heart rate decreased (135 ± 15 before HFOV vs 115 ± 14 min^{− 1} during HFOV) and mean systolic blood pressure increased (before 43 ± 4 vs 51 ± 4 mmHg during HFOV) significantly, whereas these parameters did not change in the RDS group. Left ventricular output increased significantly in the PIE group (210 ± 34 before vs 245 ± 36 ml/kg per min during HFOV; p < 0.004), but not in the RDS group (225 ± 46 before vs 248 ± 47 ml/kg per min during HFOV; k < 0.05). Shortening fraction and systemic resistance did not change in either group. In the PIE group, mean blood flow velocities in the internal carotid artery (+ 59 %), anterior cerebral artery (+ 65 %) and celiac artery (+ 45 %) increased significantly but did not change in the RDS group. Conclusions: The results show that HFOV as used in this study, improves oxygenation, CO₂ elimination, and circulation in infants with RDS and PIE. However, systemic, cerebral, and intestinal circulation improved more in neonates with PIE than in those with RDS. This may be due to higher pulmonary compliance in infants with PIE when compared to those with RDS. Received: 15 May 1996 Accepted: 31 January 1997