Atrial natriuretic factor in chronic obstructive lung disease with pulmonary hypertension. Physiological correlates and response to peptide infusion.

To investigate the physiological role of atrial natriuretic factor (ANF) in patients with hypoxic pulmonary hypertension secondary to chronic obstructive lung disease (COLD), we infused synthetic alpha-human ANF in seven such patients, and investigated the physiological correlates to circulating peptide levels in 24 patients with COLD. ANF infusion, at incremental rates of 0.01, 0.03, and 0.1 micrograms/kg.min, increased basal plasma immunoreactive (ir) ANF (136 +/- 38 pg/ml) by 3-, 10-, and 26-fold, respectively, and reduced pulmonary artery pressure (from 33 +/- 3 to 25 +/- 2 mmHg, P less than 0.001) and systemic arterial pressure (from 88 +/- 4 to 79 +/- 4 mmHg, P less than 0.001) in a dose-related fashion. Cardiac index increased by 13.5% (P less than 0.01) while heart rate was unchanged. Cardiac filling pressures decreased at 0.1 micrograms/kg.min ANF. Pulmonary and systemic vascular resistance fell by 37% (P less than 0.001) and 19% (P less than 0.001), respectively. Arterial oxygenation was impaired during ANF infusion, suggesting partial reversal of hypoxic pulmonary vasoconstriction. Plasma renin activity remained unchanged but aldosterone fell by 44% (P less than 0.01). The levels of plasma irANF in 24 patients correlated directly with the degree of hemoconcentration (r = 0.67, P less than 0.001), respiratory acidosis (r = -0.65, P less than 0.001), and pulmonary hypertension (r = 0.52, P less than 0.01). The results suggest that ANF may serve as a potent pulmonary vasodilator involved in the circulatory homeostasis of patients with COLD.

A clinical study of intravenous cibenzoline in selected patients with recent-onset atrial tachyarrhythmia.

Twenty-five adult patients with sustained atrial tachyarrhythmia (ATA) and without heart failure were treated by intravenous cibenzoline, 1 mg/kg, as a slow bolus infusion, followed by a 8 mg/kg/24 h continuous infusion. Sinus rhythm conversion was observed in 18 patients (72 percent success rate). Severe adverse cardiac events were observed in only one patient (4 percent occurrence rate), as a wide QRS complex tachycardia finally requiring a semiemergency direct-current cardioversion. Two minor side effects were additionally observed. A similar population of 21 patients was conventionally treated with amiodarone, either given intravenously, 15 to 20 mg/kg/24 h, or orally, 30 mg/kg/24 h as a single dose. An identical success rate (15/21; 71 percent) was observed. Our results indicate that in selected patients with ATA, cibenzoline and amiodarone are highly effective for producing sinus rhythm conversion. We suggest that the former drug may be used as a first-line treatment. In case of failure, the latter may constitute an alternative to transthoracic electrical countershock.

Spontaneous pneumothorax. Comparison of thoracic drainage vs immediate or delayed needle aspiration.

In the first part of this study, 61 patients admitted for the first episode or the first recurrence of a spontaneous pneumothorax (SP) were randomly treated with thoracic drainage (TD; 28 patients) or with simple needle aspiration (NA; 33 patients). Success rate of therapy was significantly higher with TD than with NA (93%, CI 84 to 100 vs 67%, CI 51 to 83; p = 0.01). Hospital stay was similar between the two groups (7 +/- 4.6 vs 7 +/- 5.6 days), mainly because NA was delayed by 72 h in 26 patients. Recurrence rates at 3 months were 29% (CI 11 to 47%) after TD, and 14% (CI 0 to 29%) after NA (p > 0.20, NS). In the second part of the study, an additional population of 35 patients was treated by immediate NA, with a success rate of 68.5% (CI 53.5 to 83.5%), and a recurrence rate at 3 months of 30% (CI 10 to 50%). Taken together, our results indicate that NA may be proposed as a first-line treatment of SP, with a successful result in two thirds of patients and recurrence in one fifth of patients. In patients who do not heal with NA, a combined risk of TD failure and short-term recurrence of 50% may be an incentive for undelayed surgical procedures.

Intravenously administered atrial natriuretic factor in patients with COPD. Effects on ventilation-perfusion relationships and pulmonary hemodynamics.

The potent pulmonary vasodilating property of atrial natriuretic factor (ANF) may alter gas exchange in patients with COPD. We examined the hemodynamic and gas exchange responses to intravenous infusion of ANF (0.01 and 0.03 ng/min/kg body weight) in eight stable patients with COPD studied during spontaneous breathing, using the inert gas elimination technique. When compared with baseline, ANF infusion was associated with a dose-dependent decrease in pulmonary artery pressure (from 27.3 +/- 2.5 to 23.9 +/- 1.8 and 20.2 +/- 1.7 mm Hg, respectively) and a dose-dependent increase in blood flow perfusing poorly ventilated and unventilated units (VA/Q < 0.1: from 5.80 +/- 2.05 to 7.25 +/- 2.5 and 12.0 +/- 5.4 percent of total blood flow, respectively; p = 0.02). However, PaO2 remained unchanged (70.2 +/- 3.6, 68.1 +/- 3.8 65.4 +/- 3.5 mm Hg, respectively) because of a significant increase in minute ventilation (VE) from 8.6 +/- 0.8 to 9.6 +/- 0.8 and 10.3 +/- 0.7 L/min (p < 0.002). Six additional COPD patients receiving intravenously administered ANF at the same dosages were studied during controlled mechanical ventilation using right heart catheterization. In these patients, pulmonary vasodilation was associated with a significant increase in venous admixture (from 12.7 +/- 2.4 to 14.4 +/- 2.9 and 17.5 +/- 3.5 percent of total blood flow, respectively; p < 0.02), and a dose-dependent reduction in arterial PO2 (from 117 +/- 17 to 110 +/- 15 and 96.4 +/- 8.8 mm Hg, respectively; p < 0.05). The present results show that ANF infusion is associated with alterations in the VA/Q relationship in patients with COPD. However, a decrease in arterial oxygenation may be prevented by an increase in VE.

Mechanisms of impaired arterial oxygenation in patients with liver cirrhosis and severe respiratory insufficiency. Effects of indomethacin.

The mechanisms of impaired arterial oxygenation that occur in certain patients with chronic liver cirrhosis are still debated. In the present study, we investigated nine cirrhotic patients with severe respiratory disability (mean PaO2, 64 +/- 5 mm Hg), using the inert gas elimination technique to assess the distribution of ventilation-perfusion (VA/Q) ratios. We also determined shunt fraction during pure oxygen breathing, both in supine and sitting positions. To test the hypothesis that vasodilating prostaglandins could contribute to alter gas exchange in such patients with cirrhosis, we examined the hemodynamic and gasometric responses to indomethacin, 50 mg IV, in six of them. During baseline conditions, patients had high cardiac index (CI, 4.9 +/- 0.2 L/min/m2), and low pulmonary (PVR, 1.78 +/- 0.37 mm Hg/L/min/m2) or systemic (SVR, 17.7 +/- 1.15 mm Hg/L/min/m2) vascular resistances. Large intrapulmonary shunt fraction was documented in each patient with a mean value of 19.6 +/- 2.7 percent. Small perfusion in low VA/Q areas was associated with shunt in only three patients (2.5 to 5.3 percent of blood flow). Arterial PO2 was negatively related to shunt (p < 0.01) and to the dispersion of blood flow distribution (p < 0.02). There was no difference between measured and predicted PaO2. Shunt estimates from the inert gas and the 100 percent O2 breathing techniques were, respectively, 19.6 +/- 2.7 percent and 21.7 +/- 3.0 percent. During 100 percent oxygen breathing, changing from supine to sitting position decreased PaO2 from 401 +/- 50 to 333 +/- 64 mm Hg (p < 0.02), while O2 shunt remained unchanged, arteriovenous difference widened, and mixed venous PO2 decreased, from 61 +/- 3 to 47 +/- 4 mm Hg (p < 0.001). Indomethacin did not improve gas exchange or VA/Q distribution and did not affect systemic or pulmonary hemodynamics. The results show that in cirrhotic patients with severe respiratory disability, intrapulmonary shunting is the main determinant of impaired gas exchange, with no evidence of a defect in oxygen diffusion or an extrapulmonary shunt. Vasodilating prostaglandins do not appear to contribute to these alterations.

Treatment of respiratory failure using minitracheotomy and intratracheal oxygenation in selected patients with chronic lung disease.

OBJECTIVE: To evaluate the efficacy of minitracheotomy (MT) insertion for intratracheal oxygen insufflation (ITO2) on arterial blood gases and survival in patients with respiratory failure from chronic lung disease. DESIGN: Open, prospective clinical study. SETTING: A 12-bed medical intensive care unit in a non-university hospital. PATIENTS: 20 patients (14 males and 6 females, mean age 74.8 +/- 2.6 years), admitted for respiratory failure and denied mechanical ventilation. INTERVENTION: Percutaneous insertion of an MT for ITO2. Arterial blood gases were drawn just prior to, then 3, 24, 48 h and 1 week after MT insertion. Data are evaluated with a two-way analysis of variance for distribution-free data (Friedman's rank sums test). MEASUREMENTS AND RESULTS: Three hours after starting ITO2, the partial pressure of oxygen in arterial blood (PaO2) and the arterial oxygen saturation (SaO2) both increased from 51.7 +/- 2.8 to 85.4 +/- 5.6 mmHg and from 79.7 +/- 3.1 to 93.7 +/- 0.9%, respectively (p < 0.001 for both), along with a slight worsening in the partial pressure of carbon dioxide in arterial blood (PaCO2), from 59.6 +/- 2.5 to 63.5 +/- 3.0 mmHg (p < 0.05). At 1 week, improvements in PaO2 and SaO2 were maintained in all patients, while PaCO2 decreased in 14 patients (mean decrease 8.3 mmHg) and increased in the remaining patients (mean 12.5 mmHg), when compared to pre-ITO2 values. Seven patients died during follow-up, leading to a success rate of 65%. Eight and 4 patients were discharged home and to a nursing home, respectively, 9 still receiving ITO2 via MT as chronic oxygen therapy. CONCLUSION: Our results suggest that MT insertion for ITO2 may be a therapeutic option in selected patients with respiratory failure from CLD.

Bedside evaluation of the resistance of large and medium pulmonary veins in various lung diseases.

To evaluate the contribution of large and medium pulmonary veins to the total pulmonary vascular resistance in various human lung diseases, we compared in 64 patients the pulmonary arterial proximal wedge pressure (Ppw), obtained when the balloon of a 7F pulmonary artery catheter was inflated with 1.5 ml air, with the distal wedge pressure (Pdw), obtained after the tip of the catheter was advanced until wedged in a small artery without balloon inflation. Ppw, reflecting the pressure in a large pulmonary vein, approximates the left atrial pressure, whereas Pdw reflects the pressure in a smaller pulmonary vein. Pdw was greater than Ppw in all 64 patients. The Pdw-Ppw gradient was 1.1 +/- 0.5 mmHg in nine patients with normal lungs and was significantly higher in 13 patients with chronic congestive heart failure (3.8 +/- 0.8 mmHg, P less than 0.01) and in 22 patients with adult respiratory distress syndrome (3.8 +/- 0.8 mmHg; P less than 0.01), but not in 20 patients with chronic obstructive pulmonary disease (1.8 +/- 0.7 mmHg). The distribution of the pulmonary vascular resistance was clearly different among the four groups. The fraction of the total pulmonary vascular resistance attributable to large and medium pulmonary veins was significantly increased (P less than 0.01) in adult respiratory distress syndrome (27.5 +/- 12%) and cardiac patients (27.5 +/- 9%) compared with patients with chronic obstructive pulmonary disease (13 +/- 5%) and normal lungs (13.5 +/- 6%).(ABSTRACT TRUNCATED AT 250 WORDS)

Involvement of ANF in the acute antidiuresis during PEEP ventilation.

To investigate the potential role of natriuretic factor (ANF) on changes on renal excretory function in response to increased intrathoracic pressure, seven patients were studied during three successive 60-min periods of 1) mechanical ventilation (MV) and zero end-expiratory pressure (ZEEP), 2) MV with 12 cmH2O positive end-expiratory pressure (PEEP), and 3) MV with the same level of PEEP while lower-body positive pressure (LBPP) was applied to restore venous return and increase central blood volume without fluid loading. Hemodynamics, renal excretory function parameters, and plasma immunoreactive atrial natriuretic factor (irANF) levels were recorded at the end of each period. Compared with ZEEP, PEEP induced a significant reduction of diuresis (from 134 +/- 17 to 59 +/- 13 ml/h, P less than 0.01) and natriuresis (from 8.37 +/- 3.5 to 3.83 +/- 2 mmol/h, P less than 0.01), whereas plasma irANF fell from 520 +/- 292 to 155 +/- 40 pg/ml (P less than 0.01) and transmural right atrial pressure decreased from 3.9 +/- 0.5 to 2.4 +/- 0.3 mmHg (P less than 0.01). Opposite changes were observed during application of LBPP, which restored diuresis and plasma irANF to near control ZEEP values, despite continuation of PEEP. Changes in renal excretory function parameters thus paralleled changes in right atrial pressure and plasma irANF. We suggest that changes in plasma irANF in response to hemodynamic variations induced by changes in intrathoracic pressure may contribute to alterations of renal excretory function during PEEP.

Hormonal interactions and renal function during mechanical ventilation and ANF infusion in humans.

To investigate the influence of atrial natriuretic factor (ANF) on renal function during mechanical ventilation (MV), we examined the renal and hormonal responses to synthetic human ANF infusion in eight patients during MV with zero (ZEEP) or 10 cmH2O positive end-expiratory pressure (PEEP). Compared with ZEEP, MV with PEEP was associated with a reduction in diuresis (V) from 208 +/- 51 to 68 +/- 11 ml/h (P less than 0.02), in natriuresis (UNa) from 12.4 +/- 3.3 to 6.2 +/- 2.1 mmol/h (P less than 0.02), and in fractional excretion of sodium (FENa) from 1.07 +/- 0.02), 0.21 to 0.67 +/- 0.17% (P less than 0.02) and with an increase in plasma renin activity (PRA) from 4.83 +/- 1.53 to 7.85 +/- 3.02 ng.ml-1.h-1 (P less than 0.05). Plasma ANF levels markedly decreased during PEEP in four patients but showed only minor changes in the other four patients, and mean plasma ANF levels did not change (163 +/- 33 pg/ml during ZEEP and 126 +/- 30 pg/ml during PEEP). Glomerular filtration rate and renal plasma flow were unchanged. Infusion of ANF (5 ng.kg-1.min-1) during PEEP markedly increased V and UNa by 110 +/- 61 and 107 +/- 26%, respectively, whereas PRA decreased from 7.85 +/- 3.02 to 4.40 +/- 1.5 ng.ml-1.min-1 (P less than 0.05). In response to a 10 ng.kg-1.min-1 ANF infusion, V increased to 338 +/- 79 ml/h during ZEEP but only to 134 +/- 45 ml/h during PEEP (P less than 0.02), whereas UNa increased, respectively, to 23.8 +/- 5.3 and 11.3 +/- 3.3 mmol/h (P less than 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)

[Medical implantable devices and electromagnetic compatibility]. / Dispositifs médicaux implantables et compatibilité électromagnétique.

Continuing progress in medicine has led to a corresponding population growth among the elderly population resulting in an increase in the number of patients with active implanted medical devices. At the same time, there continues to be a proliferation of electromagnetic wave sources within our technological environment. The coexistence of implanted active medical devices and environmental electromagnetic waves requires particular attention in order to avoid electromagnetic interference. For this reason, experts are more and more involved in writing specific manufacturing standards.

[Efficacy of intravenous administration of calcium on sinus dysfunction developed under diltiazem. Apropos of 4 cases]. / Efficacité de l'administration de calcium intraveineux sur une dysfonction sinusale apparue sous diltiazem. A propos de 4 observations.

Four cases of sinus node dysfunction with junctional escape which developed during oral treatment with diltiazem in the usual therapeutic doses (180 to 240 mg/day) are reported. In one case the cardiac toxicity of diltiazem may have been potentiated by amiodarone taken concomitantly. In two cases a biological liver alteration may have modified the metabolism of diltiazem by slowing down its degradation. In all 4 patients, a slow intravenous injection of 1 g of calcium chloride resulted in rapid and lasting restoration of a normal sinus rhythm, making temporary ventricular pacing unnecessary. The authors underline the value of calcium administration as a therapeutic test in all disorders of cardiac rhythm or conduction occurring in patients treated with calcium channel blocking agents.

[Nitric oxide, from vascular physiology to therapeutics]. / Le monoxyde d'azote, de la physiologie vasculaire à la thérapeutique.

Nitric oxide (NO) synthesised by endothelial cells, plays a key role in the control of vascular tone. Its synthesis from L-arginine is assured by NO-synthase, the activity of which is dependent on intracellular calcium concentrations, which are themselves modulated by pharmacological (acetylcholine, serotonin, bradykinin...) or physical factors (shearing forces exerted by blood flow). NO acts by stimulating a soluble guanylate-cyclase of the smooth muscle cells in the vessel wall. Its vasodilator effect is therefore mediated by an increase in intracellular cyclic GMP concentration. The synthesis or liberation of NO by the endothelium may be decreased or abolished during many pathological processes (hypercholesterolaemia, atherosclerosis, systemic or pulmonary hypertension...). The significance of this abnormality of NO-mediated endothelium-dependent vasodilation in different pathological conditions has not been established. However, it is probably significant in view of the different properties of NO: vaso-relaxation, antiaggregant and inhibition of vascular smooth muscle growth. It is not yet known whether this abnormality is a cause or a consequence of the underlying disease. From the therapeutic point of view, NO is an active metabolite of nitrate derivatives, sodium nitroprussiate and molsidomine which therefore share the same mode of action as the so-called "endothelium-dependent" vasodilatoe agents. The inhalation of NO, which is increasingly used in neonatal and adult intensive care units, is an alternative therapeutic approach in many conditions associated with pulmonary hypertension.

[Sinusal dysfunction secondary to the ingestion of diltiazem, cured by the administration of intravenous calcium]. / Dysfonction sinusale secondaire à la prise de diltiazem corrigée par administration de calcium intraveineux.

An elderly patient, receiving long-term oral diltiazem at the usual dosage, presented a sudden attack of junctional bradycardia at 35 b X min-1; this was badly tolerated by the patient. The diltiazem blood level was normal. After recovery, nodal investigations were also normal. The treatment of this accident due to a calcium-blocker is stressed: the intravenous injection of a calcium salt only was sufficient, with a return to near-normal sinus function, so avoiding the necessity of pacing.

[Motor block induced by spinal injection of pethidine. Quantification and comparison with lidocaine]. / Bloc moteur induit par la péthidine intrarachidienne. Quantification et comparaison avec la lidocaïne.

Intrathecal pethidine (or meperidine) at a dose of 1 mg.kg-1 has proved to be effective and useful for surgical procedures by producing a spinal nerve block due to its local anaesthetic properties. Motor blockade was assessed by dynamometric measurement of the dorsal flexion of foot in ten ASA I patients after subarachnoid pethidine, and in seven ASA I patients after subarachnoid 5% lidocaine at the same dosage. Measurements were made every 5 min during the first 30 min, then every 15 min until complete motor block recovery was obtained. Values were expressed as a percentage of the initial muscle strength registered before lumbar puncture. The two drugs gave a dramatic and similar decrease in muscle strength (92 vs 95%; NS). However, the delay of maximal effect was significantly longer with pethidine than with lidocaine (33.5 +/- 14 min vs 19 +/- 5.6 min; p less than 0.05). The duration of the motor blockade was similar for both drugs (116 vs 106 min) and the 25%-75% time intervals were identical (32 +/- 14 min vs 33 +/- 12.6 min). Two severe respiratory depressions were observed with pethidine, which were rapidly reversible by intravenous naloxone. Numerous other minor side-effects occurred more frequently with meperidine than with lidocaine. It was concluded that dynamometry gave an accurate description of motor blockade induced by spinal anaesthesia.

[Treatment of severe injuries of the lower limbs. Identification of clinical criteria of severity]. / Traitement des traumatismes graves des membres inférieurs. Individualisation de critères cliniques de gravité.

The choice and timing of therapeutic methods for injuries of the lower limbs were evaluated in 60 patients. Primary amputation had to be performed in 18 of them, and conservative treatment was attempted in the others. Sixteen secondary amputations were necessary, mostly for arterial lesions. These results were not in agreement with the general severity of injury, as evaluated by the Injurity Severity Score. There was a significant difference in mortality depending on whether it was decided to amputate secondarily or to preserve the limb. When local signs of complication were present, this difference was highly significant. Age over 50 and arterial lesions were aggravating factors. When present together with an already high severity score, these factors should suggest immediate amputation as a life-saving measure.

A clinical study of amiodarone as a single oral dose in patients with recent-onset atrial tachyarrhythmia.

Forty-five patients with recent-onset sustained atrial tachyarrhythmia (mean heart rate at entry; 140.0 +/- 3.5 beats.min-1) associated with various cardiovascular diseases were treated by oral amiodarone, given as a single loading dose of 25.7 +/- 0.9 mg.kg-1 body weight. Conversion to sinus rhythm was observed in 29 patients during the first 24 h of treatment, leading to a success rate of 64.4%. Five additional patients converted to sinus rhythm with continuation of oral amiodarone, (10-15 mg.kg-1 by day) with a mean delay of 4.2 days. A similar population of 27 patients (mean heart rate at entry; 140 +/- 3 beats.min-1) was treated by intravenous amiodarone, given as a bolus infusion of 3-5 mg.kg-1 over 30 min (mean; 4.1 +/- 0.2 mg.kg-1), followed by a continuous infusion of 10-15 mg.kg-1 for 24 h (mean; 11.1 +/- 0.7 mg.kg-1). Eighteen patients converted to sinus rhythm during the first 24 h of therapy, leading to a success rate of 66.7%. Minor adverse effects of therapy were observed in two patients given oral amiodarone, and in seven given intravenous amiodarone. No major effect was observed. We suggest that amiodarone given as a single oral loading dose of 25-30 mg.kg-1 body weight is an effective, simple and well-tolerated therapy, suitable for most patients with recent-onset ATA.

Complete sinus arrest during diltiazem therapy; clinical correlates and efficacy of intravenous calcium.

The occurrence of severe sinus node dysfunction in 10 patients (three males and seven females; mean age 78.5 +/- 3.4, range 57-92 years) receiving oral diltiazem therapy (mean 190 +/- 20 mg/24 h, range 90-300) is described. Six of them were concomitantly taking amiodarone and/or beta-blocking agents. On admission, seven patients exhibited systemic hypotension and nine complained of asthenia and/or dizziness or drowsiness. ECG findings showed in all a persistent sinus arrest with atrial, junctional or ventricular escape, leading to a mean heart rate of 40.2 +/- 3 beats.min-1 (range 25-56). All patients had chronic renal failure on biological tests, with a mean endogenous creatinine clearance of 25 +/- 3 ml.min-1 (range 12-36). Intravenous calcium hydrochloride (mean 1.4 +/- 0.2 g, range 1-2), given in nine patients, rapidly restored stable sinus activity in seven. We suggest that diltiazem should be given cautiously to ageing patients with chronic renal failure, and confirm the efficacy of intravenous calcium in reversing calcium channel blocker toxicity on sinus node.