Are low-molecular-weight heparins useful for the prophylaxis and treatment of arterial thrombi?

The pharmacologic specificity of low-molecular-weight heparins (LMWHs) has enabled multiple attractive developments in the prophylaxis and treatment of arterial thrombosis. Their high antithrombotic potency associated with a potentially lower induced bleeding risk, the lack of platelet interaction, the prevention of myointimal hyperplasia, and the lower incidence of heparin-induced thrombocytopenia, are major advantages. New studies in cardiology and vascular surgery demonstrate a high efficacy for LMWHs associated with a low risk.

Mechanisms of increased myocardial contractility with hypertonic saline solutions in isolated blood-perfused rabbit hearts.

Hypertonic saline improves organ perfusion and animal survival during hemorrhagic shock because it expands plasma volume and increases tissue oxygenation. Because both decreased and increased myocardial performance have been reported with hypertonic saline, the effects of hyperosmolarity and the mechanism accounting for it were investigated in isolated blood-perfused rabbit hearts. Coronary blood flow (CBF), myocardial contractility, relaxation, and oxygen consumption were measured during administration of blood perfusates containing 140-180 mmol sodium concentrations ([Na+]). In two other series of experiments, the role of Na(+)-Ca2+ exchange in the inotropic effect of hyperosmolarity (160 mmol sodium concentration) and hypertonicity (sucrose) were also investigated. Hypertonic [Na+] induced a significant increase in contractility and relaxation, combined with a coronary vasodilation. Myocardial oxygen consumption (MVO2) increased at all hypertonic [Na+] without significant change in coronary venous oxygen tension (PVO2) and content (CVO2). Amiloride (0.3 mmol) inhibited the improved contractility observed with 160 mmol sodium. Similar Na(+)-Ca2+ exchanger blockade did not inhibit the inotropic effect of sucrose. These results confirm the positive inotropic effect of hypertonic [Na+]. The inhibition of this improvement by amiloride suggests that calcium influx through the sarcolemna could be the major mechanism of this effect.

In vitro effects of eltanolone on rat myocardium.

BACKGROUND: Eltanolone is a new short-acting intravenous induction agent. However, its effects on intrinsic myocardial contractility remain unknown. METHODS: The effects of eltanolone and its solvent (soya bean emulsion) on the intrinsic contractility of rat left ventricular papillary muscles were investigated in vitro (Krebs-Henseleit solution, 29 degrees C, pH 7.40, Ca2+ 0.5 mM, stimulation frequency 12 pulses/min). We studied contraction; relaxation; contraction-relaxation coupling under high and low loads; and postrest potentiation. RESULTS: Eltanolone (0.1, 0.3, 1, 3, and 10 micrograms.ml-1) induced no significant inotropic effect, as shown by the lack of changes in maximum unloaded shortening velocity and active isometric force. Eltanolone did not significantly modify the contraction-relaxation coupling under low load, suggesting that it did not modify calcium uptake by the sarcoplasmic reticulum. Eltanolone did not significantly modify the contraction-relaxation coupling under high load, suggesting that it did not modify calcium myofilament sensitivity. Eltanolone decreased the postrest potentiation in a concentration-dependent manner (from 150 +/- 14% to 118 +/- 9% at 10 micrograms.ml-1, P < 0.001), suggesting a decrease in the maximum capacity of calcium release by the sarcoplasmic reticulum, whereas its solvent did not. However, eltanolone did not slow postrest potentiation recovery, as shown by the absence of significant changes in the recovery slope, tau (4.5 +/- 1.4 vs. 3.8 +/- 1.0 beats; difference not statistically significant). CONCLUSIONS: Eltanolone induced no significant inotropic effect on rat myocardium. It induced a decrease in the calcium release function of the sarcoplasmic reticulum, but this effect was not sufficiently important to modify the inotropic properties.

Plasma ionized calcium in brain-dead patients.

BACKGROUND: The mechanism of brain death-induced myocardial dysfunction remains debatable. Hypocalcemia is known to induce reversible myocardial dysfunction. However, the incidence of hypocalcemia and its effect on myocardial function during brain death is unknown. METHODS: In 54 consecutive brain-dead patients, we measured plasma total and ionized calcium concentrations, QT and corrected QT intervals, and left ventricular ejection fraction area (LVEFa), using transesophageal echocardiography. RESULTS: 49 (91%) of brain-dead patients had a decrease in total plasma total calcium concentration but only 19 (35%) had a decrease in plasma ionized calcium. Corrected total plasma calcium failed to predict ionized calcium concentration and QT intervals were not significantly different in normo and hypocalcemic patients. The LVEFa was not significantly different between normo and hypocalcemic patients (53 +/- 13 versus 50 +/- 20%), and no correlation was found between LVEFa and ionized calcium (R = 0.02, NS). Hypocalcemic patients required greater doses of dopamine (8.2 +/- 5.2 versus 5.0 +/- 3.4 micrograms.kg-.min-1, p < 0.02) to maintain arterial pressure. Hypocalcemia was associated with a higher volume loading and a lower plasma protide concentration which reflected hemodilution. CONCLUSION: A decrease in plasma ionized calcium is not frequent, rarely severe, and probably not the main mechanism of myocardial dysfunction in brain-dead patients. Hypocalcemic patients required higher doses of dopamine, suggesting a decrease in systemic resistance. Only direct measurement of ionized calcium can assess plasma calcium ion status in brain-dead patients.

Determinants of systolic pressure variation in patients ventilated after vascular surgery.

OBJECTIVE: To discover the predominant determinant of systolic pressure variation during positive-pressure ventilation in mechanically ventilated patients after a vascular surgical procedure. DESIGN: Case control study. SETTING: Postanesthesia care unit at a university hospital. PARTICIPANTS: Eleven patients who were sedated during mechanical ventilation after abdominal aortic surgery. INTERVENTIONS: Radial arterial pressure and airway pressure were simultaneously recorded. The systolic pressure variation was measured as the mean difference between the maximal and minimal systolic pressure values during five consecutive mechanical breaths. The delta down was measured as the difference between the systolic blood pressure during apnea and the minimal values of the systolic pressure after one mechanical breath. The velocity time integral, which is closely related to stroke volume, was measured throughout the systolic pressure measurements. MEASUREMENTS AND MAIN RESULTS: Positive correlation was found between changes in velocity time integral and the magnitude of both systolic pressure variation (r = 0.73) and delta down (r = 0.80). Volume loading did not significantly modify systolic blood pressure. However, it did not significantly decrease systolic pressure variation and delta down. The corresponding changes in velocity time integral provoked by mechanical ventilation decreased significantly as well. CONCLUSIONS: The decrease in systolic pressure provoked by positive-pressure inspiration reflects simultaneous decreases in stroke volume. This suggests that a decrease in left ventricular filling, associated with positive-pressure inspiration, is responsible for systolic pressure variation. This finding confirms the interest in considering systolic pressure variation to provide reliable information about the responsiveness of the heart to preload variations.

Systemic gas embolism complicating pulmonary contusion. Diagnosis and management using transesophageal echocardiography.

Systemic air embolism has been frequently reported after penetrating thoracic trauma. In blunt thoracic trauma, systemic air embolism has been rarely diagnosed, and then only after an invasive procedure such as thoracotomy. Transesophageal echocardiography has been recently introduced for the early assessment of trauma patients and is considered a sensitive noninvasive procedure to diagnose air embolism. We report three cases of systemic air embolism in patients with pulmonary contusion secondary to a blunt thoracic trauma requiring controlled ventilation. Transesophageal echocardiography was performed for evaluation of hemodynamic instability, and it showed air bubbles in the left atrium and left ventricle during the insufflation phase, which disappeared during apnea. A decrease in airway pressure (release of PEEP, low tidal volume, high frequency jet ventilation) significantly reduced the systemic air embolism. We concluded that systemic air embolism can occur after blunt thoracic trauma, and transesophageal echocardiography enables a rapid and accurate diagnosis that may be useful for therapeutic management.

Circulating cardiac troponin T in potential heart transplant donors.

BACKGROUND: Brain death may induce myocardial dysfunction, the mechanisms of which are not yet fully understood. Circulating cardiac troponin T is considered a highly sensitive and specific marker of myocardial cell injury. METHODS AND RESULTS: We prospectively measured circulating cardiac troponin T in 100 brain-dead patients and measured the left ventricular ejection fraction area (LVEFa), using transesophageal echocardiography. Sixty-one patients had normal LVEFa, 25 had moderate decrease in LVEFa (30% to 50%), and 14 had severe decrease in LVEFa (< or = 30%). Circulating cardiac troponin T concentrations were significantly higher (1.68 +/- 1.03 micrograms/L-1, P < .01) in patients with a severe decrease in LVEFa than in the two other groups (0.42 +/- 0.43 and 0.12 +/- 0.16 microgram/L-1, respectively), and there was a significant correlation between LVEFa and cardiac troponin T concentration (p = -0.59, P < .0001). An elevated circulating cardiac troponin T concentration (> or = 0.5 microgram/L-1) was more accurate (sensitivity, 1.00; specificity, 0.84) in predicting a severe decrease in LVEFa than an elevated CKMB value or an increased CKMB/CK ratio. CONCLUSIONS: An elevated circulating cardiac troponin T was associated with a severe decrease in LVEFa in brain-dead patients, suggesting that severe and potentially irreversible myocardial cell damage occurred. In contrast, CKMB determination was not useful. Since the quality of the donor's heart is considered an important prognosis factor in heart transplantation, the determination of circulating cardiac troponin T concentration could be useful to the heart transplantation team.

Inferences about respiratory muscle use after cardiac surgery from compartmental volume and pressure measurements.

BACKGROUND: After upper abdominal surgery, patients have been observed to have alterations in respiratory movements of the rib cage and abdomen and respiratory shifts in pleural and abdominal pressure that suggest dysfunction of the diaphragm. The validity of making such deductions about diaphragm function from these observations is open to discussion. METHODS: In eight adult patients, American Society of Anesthesiologists physical status 2, scheduled for elective cardiac surgery, we measured respiratory rate, tidal volume, rib cage and abdominal cross-section changes, and esophageal (Pes) and gastric (Pga) pressures preoperatively, 1 day postoperatively, and 5 days postoperatively. These data were analyzed in detail by following the variables through each respiratory cycle. RESULTS: Mean delta Pga/delta Pes decreased from 0.73 preoperatively to -0.56 1 day postoperatively and recovered to 0.47 5 days postoperatively. Plots of Pes against Pga and rib cage against abdominal expansion (Konno-Mead diagrams) were constructed. Six patients showed a postoperative pattern of breathing similar to that seen in patients who have undergone abdominal surgery: a decrease in the ratio of delta Pga/delta Pes and a shift toward rib cage expansion, with an increase in breathing rate and a decrease in tidal volume. This change was accomplished in most cases by the use of abdominal muscles in expiration with an increase in inspiratory intercostal muscle action without an increase in diaphragm activation, that is, a shift in the normal balance of respiratory muscle use in favor of muscles other than the diaphragm. A different ventilatory pattern was observed in the other two patients, consisting of minimal rib cage excursion and a large abdominal excursion. In these cases tidal volume was generated largely by contraction and relaxation of abdominal muscles with probable reduction in diaphragm activity. In addition, five patients exhibited positive changes in Pes at the end of inspiration that corresponded to closure of the upper airway, relaxation of inspiratory muscles, and subsequent opening of the airway with sudden exhalation, producing a grunt. CONCLUSIONS: Indirect measurements of respiratory muscle action based on pressure and chest wall motion are easier than are assessments based on implanted electromyogram electrodes and sonomicrometers that measure electric activity and muscle length, respectively, directly. Interpretation requires numerous assumptions and detailed analysis of phase relations among the variables. In patients after thoracic surgery, however, these measurements strongly point to a shift in the distribution of motor output toward muscles other than the diaphragm.

Cardiovascular consequences of severe hypophosphataemia in brain-dead patients.

Hypophosphataemia is known to induce reversible myocardial dysfunction, but the incidence of hypophosphataemia and its effect on myocardial function during brain death are unknown. In 90 consecutive brain-dead patients, we measured plasma concentrations of phosphate and left ventricular ejection fraction area (LVEFa), using transoesophageal echocardiography. In 15 severely hypophosphataemic (< 0.40 mmol litre-1), consecutive, brain-dead patients, haemodynamic status, LVEFa, and oxygen delivery and consumption were assessed before and after phosphorus loading (0.30 mmol kg-1). In 10 other brain-dead patients, urine elimination of phosphates was measured. Only 30 (33%) brain-dead patients had normal plasma phosphate concentrations, 22 (24%) had mild hypophosphataemia (0.40-0.80 mmol litre-1) and 38 (42%) had severe hypophosphataemia (< 0.40 mmol litre-1). There were no significant differences in LVEFa between these three groups (mean 53 (SD 16), 55 (12) and 51 (17)%, respectively) and no significant correlation between LVEFa and plasma phosphate concentration (r = 0.04). In 15 severely hypophosphataemic patients, phosphorus loading increased plasma phosphate concentration from 0.30 (0.10) to 1.06 (0.41) mmol litre-1, but did not modify haemodynamic status, LVEFa or oxygen delivery and consumption. In 10 other patients, urine phosphorus elimination was 16.8 (23.3) mmol/24 h while plasma phosphate concentration was at its highest level (0.80 (0.37) mmol litre-1), and only one of these patient had a slightly elevated phosphaturia. In conclusion, hypophosphataemia frequently occurs after brain death but has no significant cardiovascular consequences, suggesting that it is related to intracellular transfer and not phosphorus depletion.(ABSTRACT TRUNCATED AT 250 WORDS)

Myocardial effects of propofol in hamsters with hypertrophic cardiomyopathy.

BACKGROUND: Propofol is a short-acting intravenous induction agent that induces cardiovascular depression but without significant effect on intrinsic myocardial contractility in various species. However, its effects on diseased myocardium remain unknown. METHODS: The effects of propofol (1, 3, and 10 micrograms.ml-1) on the intrinsic contractility of left ventricular papillary muscles from normal hamsters and those with hypertrophic cardiomyopathy (strain BIO 14.6, aged 6 months) were investigated in vitro (Krebs-Henseleit solution, 29 degrees C, pH 7.40, Ca++ 2.5 mmol.l-1, stimulation frequency 3/min). RESULTS: Cardiac hypertrophy (143 +/- 13%, P < 0.001) was observed in cardiomyopathic hamsters. The contractility of papillary muscles from hamsters with cardiomyopathy was less than that of controls, as shown by the decrease in maximum shortening velocity (-29%, P < 0.03) and active isometric force (-51%, P < 0.001). Propofol did not induce any significant effect on contraction, relaxation, and contraction-relaxation coupling under low and high loads in normal hamsters. The effects of propofol were not significantly different between normal hamsters and those with cardiomyopathy. A slight but significant increase in maximum unloaded shortening velocity was observed in cardiomyopathic hamsters at 3 micrograms.ml-1 (4 +/- 6%, P < 0.05) and 10 micrograms.ml-1 (7 +/- 6%, P < 0.05). CONCLUSIONS: Propofol did not modify intrinsic myocardial contractility in normal hamsters, and no significant differences were observed between normal and cardiomyopathic hamsters. These results may be useful because, unlike propofol, most anesthetics decrease myocardial contractility. Nevertheless, indirect cardiac effects of propofol may be more important than its direct cardiac effects in patients with impaired cardiac function.

[Combination of propofol-sufentanil on somatosensory evoked potentials in surgery of the spine]. / Effets de l'association propofol-sufentanil sur les potentiels évoqués somesthésiques au cours de la chirurgie du rachis.

OBJECTIVES: Most anaesthetics depress cortical somatosensory evoked potentials (CSEPs). However, the modification of CSEPs during total intravenous anaesthesia using propofol remaining still unknown, justified this trial. TYPE OF STUDY: Open, prospective, clinical study. METHODS: Nine consecutive patients requiring CSEPs monitoring for spine surgery, were studied. Anaesthesia was induced with propofol (2.5 mg.kg-1 then 10 mg.kg-1.h-1) and sufentanil (0.50 micrograms.kg-1 then 0.25 micrograms.kg-1.h-1). Maximum positive (P40) and negative (N50) waweform latencies, and the peak to peak amplitude of CSEPs (posterior tibial nerve stimulation, cortical recording), were recorded before induction, 30 min, 1 and 2 h after induction, and at the end of surgery. Data are means +/- SD. RESULTS: Duration of anaesthesia was 260 +/- 73 min. Propofol induced significant lengthening of CSEPS (P40: from 37 +/- 10 up to 41 +/- 11 ms; N50: from 45 +/- 11 up to 51 +/- 14 ms), and a significant decrease in amplitude (from 1.9 +/- 0.9 down to 0.8 +/- 0.4 microV), but these changes were stable from 30 min after the induction to the end of spine surgery. A motor response was obtained 29 +/- 14 min after the end of anaesthetic administration. CONCLUSIONS: Total intravenous anaesthesia with propofol and sufentanil induces a small but stable lengthening of CSEPs latency and a stable decrease of its amplitude, which enable an appropriate monitoring of CSEPs during spine surgery.

[Effects of platelet-rich plasma on hemostasis and transfusion requirement in vascular surgery]. / Effets du plasma riche en plaquettes sur l'hémostase et le besoin transfusionnel en chirurgie vasculaire.

OBJECTIVE: To assess the effect of intraoperative autologous platelet-rich plasma (PRP) transfusion on haemostasis, blood loss and blood requirements during vascular surgery. STUDY DESIGN: Randomized clinical trial. PATIENTS: Twenty patients undergoing elective abdominal infrarenal aortic aneurysmectomy, using autologous transfusion techniques (predonation programme and/or preoperative normovolaemic haemodilution and/or intraoperative use of a cell-saver), were randomly allocated either into the PRP group (n = 10) or the Control group (n = 10). METHOD: In patients of PRP group, 10 mL.kg-1 of PRP were obtained over 40 to 50 min, prior to induction of anaesthesia, and compensated simultaneously with an equivalent amount of hydroxyethyl starch. Each PRP unit was transfused to its donor after aortic declamping. Blood samples were obtained before induction, before incision, at wound closing and at the end of PRP unit transfusion for determination of biological variables. RESULTS: The PRP units transfused in the patients of PRP group contained 755 +/- 117 mL of plasma with a platelet count of 62 +/- 31 G.L-1. The intra and postoperative blood losses were similar in both groups (1622 +/- 758 and 233 +/- 322 mL respectively in PRP group vs 1890 +/- 1331 and 291 +/- 303 mL respectively in Control group). In both groups, three patients required an additional transfusion of homologous blood. The results of biological tests (haematocrit, platelet and white cell counts, prothrombin time, aPTT, thrombin time, fibrinogen, D-dimers, proteins, calcium) were also similar between groups at the various times of sampling. The reinfusion of the PRP unit did not increase the platelet count. CONCLUSIONS: This study demonstrates that intraoperative infusion of autologous PRP does not decrease blood loss and homologous transfusion requirements in patients undergoing elective abdominal infrarenal aortic aneurysmectomy. This result can be related to the relatively moderate enrichment in platelets obtained with the centrifugation speed used in this study.

Aprotinin to decrease bleeding and intraoperative blood transfusion requirements during descending thoracic and thoracoabdominal aortic aneurysmectomy using cardiopulmonary bypass.

The purpose of this retrospective study was to assess the efficacy of aprotinin, an antifibrinolytic agent, in reducing bleeding and blood transfusion requirements in patients undergoing descending thoracic or thoracoabdominal aortic aneurysmectomy using cardiopulmonary bypass (CPB). Sixty-nine consecutive patients underwent thoracic or thoracoabdominal aneurysmectomy using CPB in a 2-year period. None of the 29 patients operated on in 1990 (group 1) received aprotinin, whereas all 40 patients operated on in 1991 (group 2) were placed on a high-dose regimen of aprotinin. There were no significant differences between the two groups. Administration of aprotinin was associated with a decrease in CPB time (p = 0.02), surgical duration (p = 0.05) and intraoperative blood loss (p = 0.008) as well as a reduction in intraoperative packed red cells (p = 0.01), Cell-Saver units (p = 0.05), fresh-frozen plasma units (p = 0.002), and platelet concentrate (p = 0.01) requirements. These data suggest that aprotinin is effective in reducing bleeding and blood transfusion requirements during descending thoracic or thoracoabdominal aortic aneurysmectomy using CPB.

High-frequency jet ventilation vs continuous positive airway pressure for differential lung ventilation in patients undergoing resection of thoracoabdominal aortic aneurysm.

Twenty patients, scheduled for surgical resection of thoracoabdominal aortic aneurysm were divided into two groups according to the type of differential lung ventilation used during graft replacement of the descending thoracic aorta. In the high-frequency jet ventilation (HFJV) group of ten patients, HFJV was applied to the left lung once collapsed and retracted by the surgeon, the patient lying in the right lateral decubitus and being intubated by a Carlens' tube. In the continuous positive airway pressure (CPAP) group of ten patients, CPAP was applied to the left lung at the same mean airway pressure as HFJV (1 kPa). Before anaesthetic induction, an arterial and a Swan-Ganz catheter were inserted for cardiovascular monitoring. The same anaesthetic technique using fentanyl 6 micrograms.kg-1, flunitrazepam 0.02 mg.kg-1 and pancuronium 0.1 mg.kg-1 was used for each patient. Haemodynamic and respiratory measurements were made; 15 min after positioning the patients in the right lateral decubitus using two-lung ventilation; 15 min after collapse and retraction of the left lung using one-lung ventilation and 15 min after using differential lung ventilation with CPAP or HFJV. Left lung collapse with conventional one-lung ventilation induced a dramatic decrease in arterial oxygenation: PaO2/FIO2 ratio decreased from 43 +/- 6 kPa to 20 +/- 8 kPa, alveolo-arterial oxygen difference increased from 24 +/- 7 kPa to 72 +/- 11 kPa and pulmonary shunt increased from 17 +/- 2% to 37 +/- 3%. Whereas differential lung ventilation with CPAP did not improve any of the respiratory parameters measured, differential lung ventilation with HFJV, significantly increased PaO2/FIO2 ratio to 41 +/- 14 kPa.(ABSTRACT TRUNCATED AT 250 WORDS)

Fiberoptic bronchoscopy in brain-dead organ donors.

Criteria for selecting lung donors include normal chest X-ray and adequate gas exchange, but normal bronchoscopy is not always required. Thus, we conducted a prospective study of fiberoptic bronchoscopy in 72 brain-dead donors scheduled for multiple organ procurement. Chest X-ray was considered normal in 37 donors (51%), and PaO2 was > 400 mm Hg with an FIO2 of 100% in 34 donors (47%). Fiberoptic bronchoscopy was normal in only 24 donors (33%). In the remaining 48 donors, inhalation of gastric contents (n = 26) or blood (n = 17), pulmonary contusion (n = 5), or purulent bronchial secretions (n = 4) were noted. In the 26 donors with normal chest X-ray and PaO2 > 400 mm Hg with FIO2 of 100%, bronchoscopy was abnormal in 10 donors (38%). In 33 donors, arteriovenous difference in oxygen content (2.4 +/- 0.8 ml O2/100 ml), and pulmonary shunt (0.30 +/- 0.11, range 0.13-0.49) were measured. In the 15 donors with PaO2 > 400 mm Hg, pulmonary shunt was 0.23 +/- 0.07 (range 0.13-0.35). Our study suggests that chest X-ray and arterial blood gas analysis are not sufficient, and that fiberoptic bronchoscopy should be routinely performed to select potential lung donors. Even in brain-dead donors, only the measurement of pulmonary shunt can precisely assess pulmonary gas exchange.

Influence of chronic angiotensin-converting enzyme inhibition on anesthetic induction.

BACKGROUND: Several cases of hypotension have been reported in patients who received angiotensin-converting enzyme inhibitors (ACEIs) before a surgical procedure, suggesting that interactions between ACEIs and anesthesia may be neither beneficial nor predictable. To determine if continuation of ACEI therapy until the morning of surgery leads to an unacceptable decrease in blood pressure on induction, we investigated 51 vascular surgical patients that were chronically treated for hypertension with either captopril or enalapril. METHODS: After randomization, ACEI therapy was either continued until the morning of surgery or stopped at the time of the preanesthetic visit, at least 12 h (captopril) or 24 h (enalapril) before surgery. Each patient received a standardized anesthetic induction. If systolic blood pressure (monitored using a radial artery cannula) decreased to less than 90 mmHg in response to induction, ephedrine was administered. RESULTS: A marked decrease in plasma converting-enzyme activity was found in patients who received enalapril until the morning of the surgical procedure, and 100% of them required ephedrine after induction. In patients who received their usual dose of captopril on the morning of surgery, plasma converting-enzyme activity was reduced to a lesser extent (when compared with patients who received enalapril). Finally, in the patients in whom ACEI therapy, either enalapril or captopril, was stopped of the evening before surgery, the incidence of induction-induced hypotension was significantly less when enalapril or captopril therapy has been discontinued. CONCLUSIONS: These data indicate that in hypertensive patients chronically treated with ACEIs, maintenance of therapy until the day of surgery may increase the probability of hypotension at induction.

Inhaled nitric oxide reverses the increase in pulmonary vascular resistance induced by permissive hypercapnia in patients with acute respiratory distress syndrome.

BACKGROUND: The aim of this prospective study was to determine if inhaled nitric oxide (NO) would reverse the increase in pulmonary arterial pressures and in pulmonary vascular resistance induced by acute permissive hypercapnia in patients with acute respiratory distress syndrome. METHODS: In 11 critically ill patients (mean age 59 +/- 22 yr) with acute respiratory distress syndrome (Murray Score > or = 2.5), the lungs were mechanically ventilated with NO 2 ppm during both normocapnic and hypercapnic conditions. Four phases were studied: normocapnia (arterial carbon dioxide tension 38 +/- 6 mmHg, tidal volume (655 +/- 132 ml); normocapnia plus inhaled NO 2 ppm; hypercapnia (arterial carbon dioxide tension 65 +/- 15 mmHg, tidal volume 330 +/- 93 ml); and hypercapnia plus inhaled NO 2 ppm. Continuous recordings were made of heart rate, arterial pressure, pulmonary artery pressure, tracheal pressure, and tidal volume (by pneumotachograph). At the end of each condition, arterial pressure, pulmonary artery pressure, cardiac filling pressures, and cardiac output were measured. Simultaneous arterial and mixed venous blood samples were obtained to measure arterial oxygen tension, arterial carbon dioxide tension, mixed venous oxygen tension, arterial hemoglobin oxygen saturation, mixed venous hemoglobin oxygen saturation, pH, and blood hemoglobin and methemoglobin concentrations (by hemoximeter). In addition, plasma concentrations of catecholamines were measured with a radioenzymatic assay. In 5 patients, end-tidal carbon dioxide tension was measured with a nonaspirative infrared capnometer. Calculations were made of pulmonary vascular resistance index, systemic vascular resistance index, true pulmonary shunt, and alveolar dead space. RESULTS: During hypercapnia, NO decreased pulmonary vascular resistance index from 525 +/- 223 to 393 +/- 142 dyn.s.cm-5.m-2 (P < 0.01), a value similar to that measured in normocapnic conditions (391 +/- 122 dyn.s.cm-5.m-2). It also reduced mean pulmonary artery pressure from 40 +/- 9 to 35 +/- 8 mmHg (P < 0.01). NO increased arterial oxygen tension (inspired oxygen fraction 1) from 184 +/- 67 to 270 +/- 87 mmHg during normocapnia and from 189 +/- 73 to 258 +/- 101 mmHg during hypercapnia (P < 0.01). NO decreased true pulmonary shunt during normocapnia (from 34 +/- 3% to 28 +/- 4%, P < 0.001) but had no significant effect on it during hypercapnia (39 +/- 7% vs. 38 +/- 8.5%). In five patients, NO resulted in a decrease in alveolar dead space from 34 +/- 7% to 28 +/- 10% in normocapnic conditions and from 30 +/- 9% to 22 +/- 10% in hypercapnic conditions (P < 0.05). CONCLUSIONS: Inhaled NO completely reversed the increase in pulmonary vascular resistance index induced by acute permissive hypercapnia. It only partially reduced the pulmonary hypertension induced by acute permissive hypercapnia, probably because the flow component of the increase in pulmonary pressure (i.e., the increase in cardiac output) was not reduced by inhaled NO. A significant increase in arterial oxygenation after NO administration was observed during normocapnic and hypercapnic conditions. A ventilation strategy combining permissive hypercapnia and inhaled NO may reduce the potentially deleterious effects that permissive hypercapnia alone has on lung parenchyma and pulmonary circulation.