Nitric oxide and prostacyclin as test agents of vasoreactivity in severe precapillary pulmonary hypertension: predictive ability and consequences on haemodynamics and gas exchange.

BACKGROUND: In patients with primary pulmonary hypertension who respond to vasodilators acutely, survival can be improved by the long term use of calcium channel blockers. However, testing for such a response with calcium channel blockers or prostacyclin (PGI2) may cause hypotension and adversely affect gas exchange. Nitric oxide (NO), which does not have these effects, could be a better test agent. METHODS: NO (10, 20, and 40 ppm for 15 minutes), PGI2 (1-->10 ng/kg/min), and oral nifedipine (10 mg, then 20 mg/h) were administered sequentially to 10 patients after determination of the 24 hour spontaneous variability of their pulmonary and systemic mean arterial pressures. Patients were considered responders if the mean pulmonary artery pressure or pulmonary vascular resistance decreased by 20% or more. RESULTS: Six patients (60%) responded to all three agents, and three to none of the agents. One patient responded to PGI2 only. In those who responded to vasodilators, NO had no major effect on gas exchange or systemic haemodynamics, while PGI2 and nifedipine both induced systemic hypotension (mean (SD) systemic arterial pressure 72 (14) versus 89 (19) mm Hg with PGI2 and 72 (15) versus 86 (17) mm Hg with nifedipine, p < 0.05) and hypoxaemia (PaO2 8.7 (1.4) versus 10.8 (1.0) kPa with PGI2 and 8.6 (1.4) versus 10.2 (1.5) kPa with nifedipine, p < 0.05) and increased venous admixture (28 (9) versus 14 (4)% with PGI2 and 22 (9) versus 13 (5)% with nifedipine, p < 0.05). CONCLUSIONS: NO inhalation can accurately predict a vasodilator response to nifedipine in patients with severe pulmonary hypertension without adverse effects on systemic haemodynamics and gas exchange. This absence of side effects may make it a more appropriate agent for testing the vasodilator response.

Effects of inhaled salmeterol and salbutamol (albuterol) on morning dips compared in intensive care patients recovering from an acute severe asthma attack.

OBJECTIVE: To assess the effect of a long-acting inhaled beta 2-agonist, salmeterol (SM), compared to a short-acting inhaled beta 2-agonist, salbutamol (or albuterol, SB) on the occurrence of morning dip (MD) in patients recovering from an acute severe asthma attack (ASA). DESIGN: Prospective study. SETTING: 18-bed, medical intensive care unit (ICU) in a university hospital. PATIENTS: 19 patients suffering from an ASA. INTERVENTIONS: Serial measurements of the peak expiratory flow rate (PEFR), arterial blood gases, vital capacity and forced expiratory volume in one second (FEV1) were performed from admission. All patients were first treated with i.v. methyl prednisolone and i.v. SB. Once the PEFR was stable and > 35% of predicted value, i.v. SB was stopped while i.v. steroids were maintained, and patients were randomised to either inhaled SB (9 patients, 400 micrograms every 4 h) or inhaled SM (10 patients, 100 micrograms every 12 h). RESULTS: The mean admission PEFR was 26.1 +/- 11.7% of the predicted value and was not different between the two groups. MD was more frequent with SB (6/9 patients) than with SM (4/10). The severity of MD, expressed in l/min fall in PEFR, was higher in SB than in SM (106 +/- 25 vs 55 +/- 37; p < 0.05). DISCUSSION: MD is frequent in ASA. In ASA, SM appears to reduce the frequency and the severity of MD more than SB. The clinical implications of this observation, particularly a lowering of mortality and a shortening of the ICU stay, remain to be investigated.

Haemodynamic and endocrinological effects of noninvasive mechanical ventilation in respiratory failure.

The aim of this study was to investigate the haemodynamic and endocrinological effects of noninvasive positive pressure ventilation (NIPPV). Eleven patients with oedema and recent hypercapnic and hypoxaemic worsening of a chronic respiratory insufficiency were included. Echocardiography, cardiac radionuclide assessment, blood catecholamines, salt and water handling hormones were measured at admission and discharge (long study (LS)). To discriminate between the action of NIPPV and other treatments, measurements were performed on the fourth day, for 4 h without NIPPV and 4 h with NIPPV (short study (SS)). NIPPV entailed a correction of P(a,CO2) and an increase of P(a,O2) in LS and SS. Oedema disappeared. Body weight decreased (from 85+/-42 to 81+/-40 kg) during LS. Systolic and mean pulmonary arterial pressure decreased in LS and SS. Right ventricular ejection fraction increased in LS. Left ventricular ejection fraction did not change. Cardiac index was normal on admission and then decreased. Natriuretic peptides and catecholamines were increased on admission, whereas plasma renin activity, aldosterone and vasopressin were normal. We suggest that in these patients, oedema can occur independently of renin-angiotensin-aldosterone-vasopressin and with a normal cardiac output. Noninvasive positive pressure ventilation allowed a correction of blood gases, associated with the resolution of oedema, a decrease in pulmonary arterial pressures and an increase in right ventricular ejection fraction.

Unusual cause of lethal pulmonary aspergillosis in patients with chronic obstructive pulmonary disease.

Two patients admitted to two different medical wards of our institution following respiratory decompensation of chronic obstructive pulmonary disease (COPD) were subsequently transferred to the same room of the medical intensive care unit (ICU) and intubated. Both patients developed invasive pulmonary aspergillosis and died soon after. Because COPD itself is rarely associated with lethal pulmonary aspergillosis, both cases were reviewed, and a retrospective investigation was conducted. Both patients had repeated sputum cultures while on the medical ward before their admission to the ICU; none of the sample grew Aspergillus spp. A. fumigatus was found in tracheal aspirates of both patients from the first day of their intubation while in the ICU. The pulmonary condition of both patients worsened, and invasive aspergillosis was diagnosed by bronchoalveolar lavage. Despite therapy with amphotericin B, the patients died 16 and 22 d after intubation, respectively. Both deaths were attributed to pulmonary aspergillosis; autopsy confirmed a massive pneumonia of the five lobes due to A. fumigatus in one patient. Investigation revealed that an air filter had been replaced 30 h before the first patient was admitted to the room. Experimental air filter replacement performed 12 d after the second patient died revealed the presence of A. fumigatus on the surface of the filters as well as a 10-fold increase in room air fungal counts during the procedure. This study shows that exposure to high concentrations of airborne Aspergillus spp. related to air filter change was associated with fatal invasive aspergillosis in two mechanically ventilated patients. Such infection can be prevented by the establishment and application of guidelines for air filter replacement.

Relationship between pulmonary oxygen consumption, lung inflammation, and calculated venous admixture in patients with acute lung injury.

OBJECTIVE: To determine in patients with acute lung injury whether increased pulmonary oxygen consumption (VO2pulm), computed as the difference between oxygen consumption measured by indirect calorimetry (VO2meas) and calculated by the reverse Fick method (VO2Fick), would: (1) correlate with the degree of lung inflammation assessed by bronchoalveolar lavage (BAL); (2) lead to an overestimation of calculated venous admixture (Qva/Qt). DESIGN: Prospective study. SETTING: University hospital, medical intensive care unit. INTERVENTION: None. MEASUREMENTS AND RESULTS: In nine mechanically ventilated patients with acute lung injury (Apache II 12 +/- 5, lung injury score 2 +/- 0.6, mean +/- SD), whole-body VO2 (VO2wb) was determined simultaneously by indirect calorimetry and the reverse Fick technique, after which BAL was immediately performed. VO2meas was significantly higher than VO2Fick (128 +/- 24 and 102 +/- 18 ml/min per m2, respectively, p < 0.001). Median VO2pulm was 25.3 ml/min per m2 (range 1.98-51.5), thus representing 19 +/- 11% of VO2wb. Total BAL cellularity was increased in all patients (median 47, range 24-200 x 10(4)/ml), as was the total polymorphonuclear (PMN) count (median 78 range 5-93 x 10(4)/ml). Macrophage counts were in the normal range. There were raised BAL levels of interleukin-6 (IL-6) (median 945, range 23-1800 ng/ml) and elastase (median 391, range 5-949 ng/ml). Median protein levels were 270 micrograms/ml (range 50-505). There was no correlation between VO2pulm and BAL cellularity, PMNs, elastase, IL-6, or protein. Qva/Qt was 31.7 +/- 8%. Qva/Qt, corrected for the presence of VO2pulm, (Qva/Qtcorr), was 30.3 +/- 8% (P < 0.01 vs Qva/Qt), a 4.2% overestimation due to VO2plum. There was no correlation between Qva/Qt or Qva/Qtcorr and VO2pulm. CONCLUSIONS: In mechanically ventilated patients with acute lung injury, VO2pulm was increased and led to a 19% underestimation of VO2wb determined by the reverse Fick method, as well as to a 4.2% overestimation of calculated Qva/Qt. Lung inflammatory activity was increased, as assessed by BAL cellularity, IL-6 and elastase levels. However, there was no correlation between VO2pulm and the intensity of pulmonary inflammation.

Effects of rapid permissive hypercapnia on hemodynamics, gas exchange, and oxygen transport and consumption during mechanical ventilation for the acute respiratory distress syndrome.

OBJECTIVE: To measure the effects of rapid permissive hypercapnia on hemodynamics and gas exchange in patients with acute respiratory distress syndrome (ARDS). DESIGN: Prospective study. SETTING: 18-bed, medical intensive care unit, university hospital. PATIENTS: 11 mechanically ventilated ARDS patients. INTERVENTION: Patients were sedated and ventilated in the controlled mode. Hypercapnia was induced over a 30-60 min period by decreasing tidal volume until pH decreased to 7.2 and/or P50 increased by 7.5 mmHg. Settings were then maintained for 2 h. RESULTS: Minute ventilation was reduced from 13.5 +/- 6.1 to 8.2 +/- 4.1 l/min (mean +/- SD), PaCO2 increased (40.3 +/- 6.6 to 59.3 +/- 7.2 mmHg), pH decreased (7.40 +/- 0.05 to 7.26 +/- 0.05), and P50 increased (26.3 +/- 2.02 to 31.1 +/- 2.2 mmHg) (p < 0.05). Systemic vascular resistance decreased (865 +/- 454 to 648 +/- 265 dyne.s.cm-5, and cardiac index (CI) increased (4 +/- 2.4 to 4.7 +/- 2.4 l/min/m2) (p < 0.05). Mean systemic arterial pressure was unchanged. Pulmonary vascular resistance was unmodified, and mean pulmonary artery pressure (MPAP) increased (29 +/- 5 to 32 +/- 6 mmHg, p < 0.05). PaO2 remained unchanged, while saturation decreased (93 +/- 3 to 90 +/- 3%, p < 0.05), requiring an increase in FIO2 from 0.56 to 0.64 in order to maintain an SaO2 > 90%. PvO2 increased (36.5 +/- 5.7 to 43.2 +/- 6.1 mmHg, p < 0.05), while saturation was unmodified. The arteriovenous O2 content difference was unaltered. Oxygen transport (DO2) increased (545 +/- 240 to 621 +/- 274 ml/min/m2, p < 0.05), while the O2 consumption and extraction ratio did not change significantly. Venous admixture (Qva/Qt) increased (26.3 +/- 12.3 to 32.8 +/- 13.2, p < 0.05). CONCLUSIONS: These data indicate that acute hypercapnia increases DO2 and O2 off-loading capacity in ARDS patients with normal plasma lactate, without increasing O2 extraction. Whether this would be beneficial in patients with elevated lactate levels, indicating tissue hypoxia, remains to be determined. Furthermore, even though hypercapnia was well tolerated, the increase in Qva/Qt, CI, and MPAP should prompt caution in patients with severe hypoxemia, as well as in those with depressed cardiac function and/or severe pulmonary hypertension.

Influence of the quality of nursing on the duration of weaning from mechanical ventilation in patients with chronic obstructive pulmonary disease.

OBJECTIVE: To evaluate the influence of nursing on the duration of weaning from mechanical ventilation in patients with chronic obstructive pulmonary disease. DESIGN: Data were collected prospectively over a 1-yr period (study year) and compared with previously collected prospective data recorded in our chronic obstructive pulmonary disease database during a 5-yr period. SETTING: The medical intensive care unit (ICU) of a university hospital. PATIENTS: Eighty-seven patients with chronic obstructive pulmonary disease. Fifteen patients had chronic obstructive pulmonary disease that required mechanical ventilation for acute exacerbation of their disease (study year), and 72 were patients with chronic obstructive pulmonary disease from the previously collected data. INTERVENTIONS: The ICU course (duration of mechanical ventilation, mortality) was recorded, as well as several respiratory parameters (pulmonary function tests and arterial blood gases in stable conditions, and nutritional status), and they were compared with an "index of nursing." MEASUREMENTS AND MAIN RESULTS: We developed an "index of nursing", comparing the effective workforce of the nurses (number and qualifications) with the ideal workforce required by the number of patients and the severity of their diseases. A value of 1.0 represented a perfect match between the needed and the effectively present nurses, whereas a lesser value signified a diminished available workforce. This index was compared with the complications and duration of weaning from mechanical ventilation. During the first 5 yrs, the duration of mechanical ventilation increased progressively from 7.3 +/- 8.0 to 38.2 +/- 25.8 days (p = .006). A significant inverse correlation between the duration of mechanical ventilation and the nursing index (p = .025) was found. In the sixth comparative year, the number of nurses increased (nursing index = 1.05) and the duration of mechanical ventilation decreased to 9.9 +/- 13 days (p < .001, yr 5 vs. yr 6). CONCLUSIONS: The quality of nursing appears to be a measurable and critical factor in the weaning from mechanical ventilation of patients with chronic obstructive pulmonary disease. Below a threshold in the available workforce of ICU nurses, the weaning duration of patients with chronic obstructive pulmonary disease increases dramatically. Therefore, very close attention should be given to the education and number of ICU nurses.

Adult and paediatric size bronchoscopes for bronchoalveolar lavage in mechanically ventilated patients: yield and side effects.

BACKGROUND: Bronchoalveolar lavage is considered a safe procedure. When performed in the mechanically ventilated patient, however, potentially harmful effects on respiratory and haemodynamic functions have been reported in which the size of the bronchoscope may play a part. Two different size bronchoscopes (adult and paediatric) were therefore investigated with regard to bronchoalveolar lavage yield and side effects. METHODS: Twenty mechanically ventilated patients underwent bronchoalveolar lavage with both adult and paediatric bronchoscopes in a randomised sequential manner. RESULTS: In a total of 45 pairs of bronchoalveolar lavage procedures no difference was noted between adult and paediatric bronchoscopes with regard to total cell yield, differential cell count, and microbiological results. Peak intratracheal pressure increased with the adult bronchoscope only. Systemic arterial pressures increased more with the adult than with the paediatric bronchoscope. PaO2 decreased with the adult but not with the paediatric bronchoscope. CONCLUSIONS: The paediatric bronchoscope offers a comparable bronchoalveolar lavage yield in mechanically ventilated patients to the adult bronchoscope, while the respiratory and haemodynamic side effects are significantly lower than with the adult size instrument.

Pulmonary vascular reactivity in severe pulmonary hypertension associated with mixed connective tissue disease.

Pulmonary vascular reactivity tests were performed in a young woman with mixed connective tissue disease and severe pulmonary hypertension. Vasoreactivity was documented in response to intravenous prostacyclin (PGI2), oral nifedipine, and inhaled nitric oxide, with quantitative differences. Nitric oxide produced a moderate lowering of pulmonary arterial pressure and resistance without any deleterious systemic effect. The use of nitric oxide in testing for pulmonary vasoreactivity merits further evaluation.

Prolonged treatment with almitrine for refractory hypoxemia in adult respiratory distress syndrome.

A 49-year-old man presented with an atypical pneumonia entailing an adult respiratory distress syndrome (ARDS). The refractory hypoxemia caused a myocardial infarction, leading us to try pharmacologic treatments. Almitrine bismesilate (AB) infusion allowed improvement of arterial oxygenation during 115 h without adverse effect. This case is, to our knowledge, the first reported prolonged treatment using AB for hypoxemia due to ARDS.

[ARDS and mechanical ventilation--"primum nil nocere"]. / ARDS et ventilation mécanique--"primum nil nocere".

Present evidence demonstrates that mechanical ventilation in patients with adult respiratory distress syndrome (ARDS) contributes to the ongoing pulmonary damage, a condition known as "ventilator lung". Data from various animal studies indicate that volume, rather than pressure, is probably the main culprit. Accordingly, clinicians should use tidal volumes smaller than those usually recommended. This approach leads to hypercapnia (i.e. so-called "permissive hypercapnia"), which seems to have very few adverse effects and might even be beneficial. Moreover, there is an added risk of atelectasis, which can be prevented by the application of positive end-expiratory pressure (PEEP). The present study reviews the pathophysiological mechanisms by which mechanical ventilation is injurious to the lung, and attempts to outline an approach aimed at minimizing such damage.

Hypoxaemia and liver cirrhosis: a new argument in favour of a "diffusion-perfusion defect".

Liver cirrhosis is sometimes associated with very severe hypoxaemia, which is thought to be the result of intrapulmonary vascular dilatations (IPVDs). These vascular abnormalities, although close to the gas exchange units, are so dilated that diffusion of oxygen molecules to their centre is impaired, causing an increase in alveolar-arterial oxygen tension difference (P(A-a)O2). On the other hand, administration of 100% oxygen provides enough driving pressure to overcome this relative diffusion defect and rules out a true intrapulmonary shunt. We report a case in which, in spite of a normal increase in arterial oxygen tension (PaO2) under 100% oxygen, exercising results in a marked impairment of oxygen exchange and a large intrapulmonary shunt. This is probably due to the increased cardiac output and preferential blood flow through these low resistance IPVDs.