Effects of two inotropic drugs,dopamine and dobutamine,on pulmonary gas exchange in artificially ventilated patients

The inotropic agents, dopamine (DP) and dobutamine (DB), both decrease PaO₂, probably by a resistribution of the ratio. The aim of this study was to assess the effect of both drugs on the ratio, using the multiple inert gas elimination method. Ten artificially ventilated patients (eight males), aged 45–74 years were investigated. Blood gases, cardiac output and concentrations of inert gases were measured before and 30 min after infusion of DB or DP. DP and DB were administered alternatively at a rate of 5 g·k^-1 min^-1. The decrease in PaO₂ was significantly greater with DP (12±9 torr) than with DB (7±9 torr) (P< 0.01) Both drugs similarly increased cardiac ouput: +2.6l·min^-1±1.4 for DP and 2.2l·min^-1±1.5 for DB. Both DP and DB significantly (P< 0.01) increased the perfusion of alveoli with (+4±7% for DP and +3±7% for DB) and (+11±8.5% for DP and +5.5±10.5% for DB) (no significant difference between the drugs). When shunt and shunt-like effect are considered together, there was a significantly greater increase in the amout of blood going to alveoli with a low ratio with DP compared to DB. Both drugs decreased the perfusion of alveoli with , but the decrease was significantly less for DB than for DP (-15±6.5% for DP and-8.5±7% for DB,p< 0.01). We conclude that dopamine induces a greater degree of hypoxaemia compared to dobutamine due to a larger increase in shunt and/or maldistribution of the ratio.     

Smoking and pulmonary diffusing capacity.

The pulmonary diffusing capacity (DLCO SB) and its two components, the capillary blood volume (Vc) and the diffusing capacity of the membrane (DMCO), expressed in absolute values and per litre of alveolar volume (VA'), were measured at rest and on exercise in healthy male smokers and nonsmokers of similar age and height, and with identical values for haemoglobin and spirographic data. DLCO, DLCO/VA', DMCO and DMCO/VA' are significantly lower in smokers, at rest and on exercise; the decrease in Vc and thetaVc/VA' in smokers at rest is due to a higher level of carboxyhaemoglobin. The decrease of DLCO, DLCO/VA', DMCO and DMCO/VA' is apparently not due to carboxyhaemoglobin or distributional factors but to anatomical lesions, probably of emphysematous nature, altering the pulmonary membrane. Formulas predicting DLCO, DMCO, Vc, DLCO/VA', DMCO/VA' and thetaVc/VA' in terms of age and height were established in smokers and in nonsmokers.     

Effect of almitrine administered by the oral route on levels of 2,3-diphosphoglycerate and on the affinity of hemoglobin for oxygen in healthy subjects

Clinical and pharmacological studies have shown that almitrine increased arterial blood oxygen partial pressure (PaO2) and tissular oxygenation. We have verified whether this drug could also increase the 2,3 diphosphoglycerate (DPG) level and so modify the oxyhemoglobin dissociation curve (ODC). Determinations performed 3 hours and 5 days after daily oral administration (1,5 mg/kg) of the drug showed no alterations of DPG and ODC in normal subjects. The presence of almitrine does not explain the observed PaO2 increase by means of a direct effect on the hemoglobin oxygen affinity. However, one cannot exclude almitrine long term effect; indeed, after 15 days, DPG levels and Hill coefficient increased significantly (p less than 0.05) but no the P50 (respectively + 1,5 mumole/gHb; +0.1 and 26.0 vs 26.5 mmHg).     

Hyperbilirubinemia does not interfere with hemoglobin saturation measured by pulse oximetry

This prospective clinical study evaluated the influence of high bilirubin plasma levels on the Nellcor pulse oximeter readings (SpO2). Twenty-nine icteric patients (mean total bilirubin 19.2 mg/dl, range 2.3-84.3 mg/dl) were compared with 46 controls. The difference between SpO2 and oxyhemoglobin percentage of hemoglobin (HbO2corr) or fractional saturation as measured by a seven wavelengths Corning Co 2500 Co-oximeter and corrected for the spectral error induced by hyperbilirubinemia in that co-oximeter was greater in icteric patients (bias and precision: 2.9% +/- 2.2% vs. 1.7% +/- 2.7%, P less than 0.03). However, icteric patients had also higher corrected carboxyhemoglobin levels (CoHbcorr) (1.8% +/- 0.7% vs. 1.3% +/- 0.8%, P less than 0.005) due to production of carbon monoxide during the catabolism of hemoglobin. Pulse oximeters read most of CoHb as oxyhemoglobin. After correcting SpO2 for carboxyhemoglobin in both groups of patients, the 99% confidence limits from the obtained regression line were the same in icteric patients (-0.81%, 1.03%) as in controls (-0.89%, 1.08%). There was thus no demonstrable direct influence of high bilirubin plasma levels on SpO2 as measured by a Nellcor pulse oximeter.     

Reestimation of the effects of inorganic phosphates on the equilibrium between oxygen and hemoglobin

In a previous paper, published in this journal, we showed that the data obtained in patients with severe ketoacidosis suggest that inorganic phosphates (K₂HPO₄) can increase their P 50 and therefore enhance tissue oxygenation without concomitant alteration of the 2,3 diphosphoglycerate (DPG) [1]. In order to test the hypothesis that K₂HPO₄ could influence the oxyhemoglobin dissociation curve (ODC) by a mecanism which was not DPG mediated we have measured the total ODC on whole blood with and without addition of 13–80 mmol/1 of inorganic phosphates. On average, the level of DPG remained unchanged when the P 50 with K₂HPO₄ was significantly higher (p>0.001) (P 50=29.9±3.7 mmHg) than when phosphates were not administered (P 50=25.5±2.8 mmHg). The relationship between P 50 (mmHg) and K₂HPO₄ (=X mmol/1) was P 50=–2.97 10^–3(X)²+0.26(X)–0.42 (r=0.78).Seeing that phosphates have an immediate action on the ODC, we calculated in our ketoacidosis patients, the relationship between the P 50, the inorganic phosphates (P_i in mg%) and the DPG in mol/gHb. Both factors exert a highly significant effect (p<0.001) on the P 50, according to the following equation: P 50=0.35 DPG+0.26 P_i+18.92 (r=0.73). Our data are important in two points. First it is useful to add inorganic phosphates to the treatment of patients with severe ketoacidosis in order to enhance their tissue oxygenation. Second they recall that the ODC is not only determined by the classical effects of temperature, pH and DPG byt also by inorganic anions, like phosphates as described by Benesh and Benesh in their pioneering work [2].This work was supported by a grant of the Fonds de la Recherche Scientifique Médicale, no 3450.29.90     

Two kidney-transplant women with therapy-resistant hypertension: diagnostic error of a renal artery stenosis.

Cases Patient 1 This was a 57-year-old woman with end-stage renal disease (ESRD)due to chronic pyelonephritis who had received a cadaver kidneygraft in July 1980 after 42 months of haemodialysis. Maintenanceimmunosuppression included azathioprine and prednisolone. Hypertensionappeared a few months after kidney transplantation (KT) andwas treated by methyldopa 250 mg three times a day. A systolo-diastolicmurmur was noticed 6 months after KT. A first graft arteriographywas performed in 1982. It revealed parietal irregularities witha <20% stenosis involving the first 2 cm of the transplantrenal artery stenosis (RAS). In 2000, hypertension became resistantto a treatment combining isradipine and atenolol. Cockroft creatinineclearance and 24 h proteinuria were 72 ml/min and 150 mg, respectively. A colour Doppler ultrasound (CDU) using a HDI 3000 machine witha 3.5 or 5 MHz sectorial transducer was performed. Peak systolicvelocity (PSV) was measured at 3.36