Evaluation of the efficacy and safety of inhaled magnesium sulphate in combination with standard treatment in patients with moderate or severe COVID-19: A structured summary of a study protocol for a randomised controlled trial.

OBJECTIVES: Basic and clinical studies have shown that magnesium sulphate ameliorates lung injury and controls asthma attacks by anti-inflammatory and bronchodilatory effects. Both intravenous and inhaled magnesium sulphate have a clinical impact on acute severe asthma by inhibition of airway smooth muscle contraction. Besides, magnesium sulphate can dilate constricted pulmonary arteries and reduce pulmonary artery resistance. However, it may affect systemic arteries when administered intravenously. A large number of patients with covid-19 admitted to the hospital suffer from pulmonary involvement. COVID-19 can cause hypoxia due to the involvement of the respiratory airways and parenchyma along with circulatory impairment, which induce ventilation-perfusion mismatch. This condition may result in hypoxemia and low arterial blood oxygen pressure and saturation presented with some degree of dyspnoea and shortness of breath. Inhaled magnesium sulphate as a smooth muscle relaxant (natural calcium antagonist) can cause both bronchodilator and consequently vasodilator effects (via a direct effect on alveolar arterioles in well-ventilated areas) in the respiratory tract. We aim to investigate if inhaled magnesium sulphate as adjuvant therapy to standard treatment can reduce ventilation-perfusion mismatch in the respiratory tract and subsequently improve arterial oxygen saturation in hospitalized patients with COVID-19. TRIAL DESIGN: A multi-centre, open-label, randomised controlled trial (RCT) with two parallel arms design (1:1 ratio) PARTICIPANTS: Patients aged 18-80 years hospitalized at Masih Daneshvari Hospital and Shahid Dr. Labbafinejad hospital in Tehran and Shahid Sadoughi Hospital in Yazd will be included if they meet the inclusion criteria of the study. Inclusion criteria are defined as 1. Confirmed diagnosis of SARS-CoV-2 infection based on polymerase chain reaction (PCR) of nasopharyngeal secretions or clinical manifestations along with chest computed tomography (chest CT) scan 2. Presenting with moderate or severe COVID-19 lung involvement confirmed with chest CT scan and arterial oxygen saturation below 93% 3. Length of hospital stay ≤48 hours. Patients with underlying cardiovascular diseases including congestive heart failure, bradyarrhythmia, heart block, the myocardial injury will be excluded from the study. INTERVENTION AND COMPARATOR: Participants will be randomly divided into two arms. Patients in the intervention arm will be given both standard treatment for COVID-19 (according to the national guideline) and magnesium sulphate (5 cc of a 20% injectable vial or 2 cc of a 50% injectable vial will be diluted by 50 cc distilled water and nebulized via a mask) every eight hours for five days. Patients in the control (comparator) arm will only receive standard treatment for COVID-19. MAIN OUTCOMES: Improvement of respiratory function and symptoms including arterial blood oxygen saturation, dyspnoea (according to NYHA functional classification), and cough within the first five days of randomization. RANDOMISATION: Block randomisation will be used to allocate eligible patients to the study arms (in a 1:1 ratio). Computer software will be applied to randomly select the blocks. BLINDING (MASKING): The study is an open-label RCT without blinding. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): The trial will be performed on 100 patients who will be randomly divided into two arms of control (50) and intervention (50). TRIAL STATUS: The protocol is Version 5.0, January 05, 2021. Recruitment of the participants started on July 30, 2020, and it is anticipated to be completed by February 28, 2021. TRIAL REGISTRATION: The trial was registered in the Iranian Registry of Clinical Trials (IRCT) on July 28, 2020. It is available on https://en.irct.ir/trial/49879 . The registration number is IRCT20191211045691N1. FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest of expediting the dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.

Resolution of Pulmonary Cement Embolism After Treatment of Rivaroxaban on Ventilation/Perfusion SPECT Image.

ABSTRACT: A 73-year-old woman took a chest radiography for medical check-up, and pulmonary cement embolism was diagnosed. She had undergone percutaneous vertebroplasty. Ventilation-perfusion imaging revealed V/Q mismatched perfusion defect on the lung. Then, she has taken rivaroxaban (orally active direct factor Xa inhibitor) for 6 months and took follow-up V/Q scan. It revealed the disappearance of previous 2 of 3 moderate V/Q mismatches. There are controversies in the role of anticoagulation in treatment of pulmonary cement embolism, and this case shows functional recovery through the perfusion scan after anticoagulation treatment.

The emergency medicine approach to the evaluation and treatment of pulmonary embolism.

Each year in the United States, up to 900,000 individuals will suffer from acute pulmonary embolism, resulting in an estimated 200,000 to 300,000 hospital admissions. Despite decades of research on the topic, the diagnosis remains elusive in many situations and the fatality rate remains significant. This issue presents a review of the current evidence guiding the emergency medicine approach to the diagnosis and treatment of pulmonary embolism. Key to this approach is the concept of risk stratification: using factors from the history and physical examination, plus ancillary tests, to guide clinical decision making. The pathophysiology of pulmonary embolism and decision-support tools are reviewed, and emergency department management strategies are described.

Methodology for ventilation/perfusion SPECT.

Ventilation/perfusion single-photon emission computed tomography (V/Q SPECT) is the scintigraphic technique of choice for the diagnosis of pulmonary embolism and many other disorders that affect lung function. Data from recent ventilation studies show that the theoretic advantages of Technegas over radiolabeled liquid aerosols are not restricted to the presence of obstructive lung disease. Radiolabeled macroaggregated human albumin is the imaging agent of choice for perfusion scintigraphy. An optimal combination of nuclide activities and acquisition times for ventilation and perfusion, collimators, and imaging matrix yields an adequate V/Q SPECT study in approximately 20 minutes of imaging time. The recommended protocol based on the patient remaining in an unchanged position during the initial ventilation study and the perfusion study allows presentation of matching ventilation and perfusion slices in all projections as well as in rotating volume images based upon maximum intensity projections. Probabilistic interpretation of V/Q SPECT should be replaced by a holistic interpretation strategy on the basis of all relevant information about the patient and all ventilation/perfusion patterns. PE is diagnosed when there is more than one subsegment showing a V/Q mismatch representing an anatomic lung unit. Apart from pulmonary embolism, other pathologies should be identified and reported, for example, obstructive disease, heart failure, and pneumonia. Pitfalls exist both with respect to imaging technique and scan interpretation.

Ventilation/Perfusion SPECT for diagnostics of pulmonary embolism in clinical practice.

AIM: The aim of this retrospective study is to illustrate clinical utility and impact of pulmonary embolism (PE) diagnostics of up to date Ventilation/Perfusion SPECT (V/P (SPECT)) applying holistic interpretation criteria. MATERIAL AND METHODS: During a 2-year period 2328 consecutive patients referred to V/P(SPECT) for clinically suspected PE were examined. Final diagnosis was established by physicians clinically responsible for patient care. To establish the performance of V/P(SPECT) negative for PE, patients were followed up by medical records for 6 months. RESULTS: Ventilation/Perfusion SPECT was feasible in 99% of the patients. Data for follow-up were available in 1785 patients (77%). PE was reported in 607 patients (34%). Normal pattern was described in 420 patients (25%). Pathology other than PE such as a pneumonia, left heart failure, obstructive lung disease, tumour was described in 724 patients (41%). Report was nondiagnostic in 19 patients (1%). Six cases were classified as falsely negative because PE was diagnosed at follow-up and was fatal in one case. Six cases were classified as falsely positive because the clinician decided not to treat. In 608 patients with final PE diagnosis, 601 patients had positive V/P(SPECT) (99%). In 1177 patients without final PE diagnosis 1153 patients had negative V/P(SPECT) (98%). CONCLUSIONS: Holistic interpretation of V/P(SPECT,) yields high negative and positive predictive values and only 1% of nondiagnostic findings and was feasible in 99% of patients. It is a responsibility and a challenge of nuclear medicine to provide optimal care of patients with suspected PE by making V/P(SPECT) available.

Outpatient tinzaparin therapy in pulmonary embolism quantified with ventilation/perfusion scintigraphy.

BACKGROUND: Out-of-hospital treatment of patients with deep-vein thrombosis (DVT) is routine in many countries regardless of frequent concomitant asymptomatic pulmonary embolism (PE) in this group. However, patients with symptoms and verified PE are still regularly treated in hospital. The objectives were to test a model for outpatient tinzaparin therapy and to evaluate its safety and efficacy in patients with symptomatic, small or medium-sized PE using quantitative ventilation/perfusion scintigraphy (qV/P SCINT) for patient selection and follow up. MATERIAL/METHODS: This prospective study included 102 patients treated with tinzaparin and warfarin for 5 days at a patient hotel. PE was quantified scintigraphically as loss of perfusion with preserved ventilation at segmental or subsegmental levels (mismatch). Points were attributed to segments of reduced ventilation (RoVent) and perfusion (RoPer). A holistic principle of interpretation was applied. Patients were excluded if they had >14 RoPer points (7 segments) or >7 RoVent points. Clinical follow-up and scintigraphy were repeated at discharge in 100 patients and after 13 months on average. RESULTS: Embolism diminished by 44% after 5 days and demanding symptoms declined. There was no thromboembolic mortality in the trial. At late follow-up, PE had not recurred in patients with resolution after 5 days. In those with insufficient early response, persistent perfusion defects were usually observed. CONCLUSIONS: The results indicate the safety and efficacy of outpatient treatment of PE according to our model and merit larger, multicenter, controlled studies.

[Diagnostic considerations in unilateral hyperlucency of the lung (Swyer-James-MacLeod Syndrome)]. / Consideraciones diagnósticas sobre el llamado síndrome del pulmón hiperclaro unilateral (síndrome de Swyer-James o de Mc-Leod).

Swyer-James-MacLeod Syndrome (SJMS) is considered to be a relatively uncommon and complex disease characterized by roentgenographic hyperlucency of one lung, lobe, or part of a lobe, due the pulmonary vascular structure and alveolar overdistension. It is sometimes associated with bronchiectasis. This syndrome seems to be an acquired disease that develops after viral bronchiolitis and/or viral pneumonia in early childhood. Microscopically, there is evidence of patchy bronchitis and bronchiolitis.SJMS is usually asymptomatic and discovered accidentally by chest radiography in a child with respiratory symptoms and should be differentiated from other causes of unilateral hyperlucency on chest radiography, such as those related to congenital bronchial and/or vascular abnormalities. Treatment includes early control of lung infections, as well as influenza and pneumococcal vaccination. Few reports of this syndrome in children have been published. We describe the case of a 12-year-old boy with unilateral hyperlucency of the lung and respiratory symptoms of acute pneumonia and discuss the main diagnostic features of this syndrome.

Consideraciones diagnósticas sobre el llamado síndrome del pulmón hiperclaro unilateral (síndrome de Swyer-James o de Mc-Leod) / Diagnostic considerations in unilateral hyperlucency of the lung (Swyer-James-MacLeod Syndrome)

El síndrome de Swyer-James o síndrome de Mc Leod, (SJML) conocido también como enfisema unilateral, es una enfermedad poco frecuente y compleja, caracterizada radiológicamente por una hiperclaridad de un pulmón, un lóbulo, o parte de un lóbulo, debido a la estructura vascular pulmonar anormal y a la distensión de los espacios alveolares. En ocasiones puede ir acompañada de bronquiectasias. La etiología de este síndrome se atribuye a una enfermedad adquirida que aparece tras una bronquiolitis y/o una neumonía vírica diagnosticada en la infancia. En el examen anatomopatológico se observa bronquitis y bronquiolitis. Usualmente es asintomático y suele descubrirse accidentalmente al realizar una radiografía de tórax en un niño con síntomas respiratorios. Debe ser diferenciado de otras causas de hiperclaridad pulmonar unilateral en la radiografía de tórax, tales como las anomalías bronquiales o vasculares. El tratamiento incluye el control precoz de las infecciones pulmonares, así como medidas de vacunación antigripal y antineumocócica. Existen pocas referencias de la enfermedad en niños por lo que consideramos de interés su descripción en un paciente de 12 años con síntomas respiratorios de neumonía aguda, señalando los aspectos diagnósticos de mayor relevancia clínica actual (AU)

Swyer-James-Mac-Leod Syndrome (SJMS) is considered to be a relatively uncommon and complex disease characterized by roentgenographic hyperlucency of one lung, lobe, or part of a lobe, due the pulmonary vascular structure and alveolar overdistension. It is sometimes associated with bronchiectasis. This syndrome seems to be an acquired disease that develops after viral bronchiolitis and/or viral pneumonia in early childhood. Microscopically, there is evidence of patchy bronchitis and bronchiolitis. SJMS is usually asymptomatic and discovered accidentally by chest radiography in a child with respiratory symptoms and should be differentiated from other causes of unilateral hyperlucency on chest radiography, such as those related to congenital bronchial and/or vascular abnormalities. Treatment includes early control of lung infections, as well as influenza and pneumococcal vaccination. Few reports of this syndrome in children have been published. We describe the case of a 12-year-old boy with unilateral hyperlucency of the lung and respiratory symptoms of acute pneumonia and discuss the main diagnostic features of this syndrome (AU)

Comparative study of solutions for pulmonary preservation using an isolated rabbit lung model.

At the University of Minnesota, University of Wisconsin (UW), modified Euro-Collins (MEC), and Marshall (M) solutions were compared as agents for pulmonary preservation in an isolated rabbit lung model. Normal saline (NS) was used as a control. The heart-lung blocks of donor rabbits were flushed with, and then preserved in, one of the solutions at 4 degrees C. Five rabbits were studied in each group. After 8 h of cold ischemia, the left lung was ventilated and reperfused with fresh venous blood from donor rabbits for 30 min. Pulmonary function was assessed by serial measurements of oxygen (O2) and carbon dioxide (CO2) tensions in blood obtained from the left atrial appendage. The ratios of wet/dry (W/D) weight of the lungs were calculated to assess the extent of pulmonary edema. After 8 h of preservation followed by 30 min of reperfusion, O2 tension was significantly higher with UW (178.36 + 1.72 mmHg). The calculated P values were UW vs NS, < 0.0001; UW vs MEC, 0.154; and UW vs M, 0.0001. CO2 tension with UW was also lower than the other solutions: UW, 35.8 +/- 0.698 mmHg; NS, 48.5 +/- 0.745 mmHg; MEC, 40.69 +/- 0.749 mmHg; and M, 44.68 +/- 0.697 mmHg. The calculated P value was UW vs NS, 0.0001; UW vs MEC, 0.0003; and UW vs M, 0.0001 using repeated-measures analysis of covariance. The W/D ratio was lower with UW as well; UW, 6.82 +/- 0.19; NS, 8.01 +/- 0.23; MEC, 7.28 +/- 0.10; and M, 7.34 +/- 0.17. The P value was < 0.001 using post-hoc tests. In this model, UW solution preserved the lungs better than the other three solutions tested and therefore warrants further clinical application.

Effects of inhaled nitric oxide on gas exchange in lungs with shunt or poorly ventilated areas.

Inhaled nitric oxide (NO) is a selective pulmonary vasodilator with beneficial effects on some lung diseases, yet conflicting results, particularly in chronic obstructive pulmonary disease, have been reported. We hypothesized that although inhaled NO would improve gas exchange in the presence of shunt (by increasing blood flow to normal areas), it could worsen gas exchange when areas of low ventilation-perfusion (VA/Q) ratio were present since these areas could be preferentially vasodilated by NO. We examined how approximately 80 ppm inhaled NO altered pulmonary gas exchange in anesthetized ventilated dogs with the following: (1) normal lungs (n = 8), (2) shunt (n = 9, 24.7% shunt) produced by complete obstruction of one lobar bronchus, and (3) VA/Q inequality (n = 8) created by partial obstruction of one lobar bronchus resulting in a bimodal VA/Q distribution with 13% perfusion of low VA/Q areas (0.005 < VA/Q < 0.1) without shunt. Inhaled No significantly reduced pulmonary arterial (p < 0.001) and wedge pressures (p < 0.01) and pulmonary vascular resistance (p < 0.01) without changing cardiac output in each group. In normal lungs, NO did not alter PaO2 or VA/Q inequality. However, with complete obstruction, shunt fell slightly (p < 0.001) with NO. In lungs with VA/Q inequality, NO variably affected VA/Q matching, which was improved in some dogs and worsened in others. In these lungs, changes in pulmonary vascular resistance of the abnormal area of the lung were negatively correlated with changes in VA/Q dispersion (logSDQ) (R = -0.85, p < 0.01) and positively correlated with PaO2 (R = 0.79, p < 0.05). We conclude that NO has net effects on pulmonary gas exchange, depending on the underlying lung pathology consistent with competing vasodilatory effects on the normal and abnormal areas that receive the gas.

Spirometry and ventilation-perfusion inequality in patients with mild allergic asthma before and during the pollen season.

Several studies on asthma have shown a low correlation between gas exchange and spirometry, especially after treatment with bronchodilators. The aim of the present study was therefore to examine both spirometry results and gas exchange during a pollen-free period and at the end of the pollen season in patients with mild and well-controlled allergic asthma. Pulmonary gas exchange was studied using a modified form of the multiple inert gas elimination technique. Lung volumes and forced expiratory flows were measured by common spirometry. During the non-pollen season, spirometry and forced expiratory flows were within the reference values in all but one patient, who had decreased indices for airway flow. Three other patients showed signs of minor gas exchange impairment. During the pollen season, FRC was slightly increased (P < 0.05) and MEF50 was slightly decreased (P < 0.05) for the group. Two patients had an increased index for gas exchange impairment (log SDQ was 0.64 and 0.59) and four patients had borderline log SDQ (0.50 to 0.56). However, the mean log SDQ was not increased in the pollen season. The results show that, both in the pollen season and in the pollen-free season, low degrees of gas exchange impairment could be present in pollen allergic asthmatic patients despite normal spirometry. The low degree of gas exchange impairment in some patients indicates the presence of airway inflammation with oedema and/or secretion. However, high degrees of ventilation-perfusion inequality were not observed in these patients where air flow rates were mainly normal.

[High oxygen breathing improves inhomogeneities of ventilation-perfusion distributions in acutely injured lungs].

Using twenty-five mongrel dogs either with or without alveolar flooding induced by oleic acid administration, the effects of high oxygen breathing (60% O2) on ventilation--perfusion (VA/Q) distributions in the lungs were systematically investigated. VA/Q distributions were examined by multiple inert gas elimination technique, from which the VA/Q values describing mean positions of perfusion (Q) and ventilation (VA) distributions against the VA/Q axis were calculated (mean Q and mean VA). As the first measure of dispersion for VA/Q distribution, the log standard deviation was estimated (log SD (Q) and logSD (VA)). As the second measure of dispersion, the area under the curve, constructed by plotting inert gas arterial-to-alveolar partial pressure differences as a function of blood-gas partition coefficient, was calculated (aAD area). High oxygen breathing slightly enhanced the dispersion of VA/Q distributions in the normal dogs but decreased that in the dogs injured with oleic acid. Therefore, we concluded that high oxygen breathing worsened the inhomogenieties of VA/Q distributions in normal lungs but did improve those in acutely injured lungs.

Pulmonary venodilation by isoflurane improves gas exchange during Escherichia coli bacteremia.

OBJECTIVE: To determine how isoflurance affects the longitudinal distribution of pulmonary vascular resistance and pulmonary gas exchange during Escherichia coli bacteremia. DESIGN: Prospective, controlled study with open-label assignment of animals to two groups. SETTING: Laboratory. SUBJECTS: Goehingen minipigs. INTERVENTIONS: Induction of acute respiratory failure by a 4-hr infusion of live E. coli bacteria in 12 animals; six animals anesthetized with methohexital/piritramide; six animals anesthetized with isoflurane. The control group consisted of four animals that received the same surgical procedure, but no E. coli infusion. Two animals were anesthetized with methohexital/piritramide and two with isoflurane, respectively. MEASUREMENTS AND MAIN RESULTS: Cardiac output and pressures were measured by means of an arterial catheter, Swan-Ganz catheter, and a left atrial catheter. Effective pulmonary capillary pressure was evaluated graphically from a pulmonary artery occlusion pressure decay. Arterial-alveolar PO2 ratio was calculated to evaluate pulmonary function. Measurements were performed before and after 1, 2, and 3.5 hrs of E. coli infusion. Statistical significance was tested with analysis of variance (ANOVA). E. coli infusion caused hypodynamic shock, an increase in pre- and postcapillary pulmonary vascular resistance and respiratory failure. Postcapillary pressure gradient and effective pulmonary capillary pressure were lower in the isoflurane-group. Methohexital-anesthetized animals developed pulmonary dysfunction after 1 hr of bacteremia, whereas isoflurane-anesthetized animals developed pulmonary dysfunction after 3.5 hrs of E. coli infusion (significantly different, ANOVA, p < .05). There were no significant changes in the sham group. CONCLUSIONS: Isoflurane is a pulmonary venodilator. During lethal E. coli infusion, it ameliorates the increase in pulmonary capillary pressure and preserves pulmonary function until vascular permeability increases.

When weaning from mechanical ventilation fails.

OBJECTIVE: To describe the etiologies and indicators of weaning failure and to provide a framework for planning interventions to facilitate weaning of long-term ventilation patients. DATA SOURCE: A Medline search of human studies in English on weaning from mechanical ventilation. ARTICLE SELECTION: Articles were selected if they pertained to the assessment and management of weaning failure. Both research and review articles were included. DATA EXTRACTION: All pertinent articles were described, along with their limitations. DATA SYNTHESIS: Weaning from mechanical ventilation is an emerging science. Caring for patients who are difficult to wean requires expert clinical decision making so patients do not feel defeated and have the best chances for success. Combining the limited research on weaning intervention with clinical expertise helps to build a scientific basis for care and can assist clinicians in tailoring interventions to specific problems that precipitate weaning failure. CONCLUSION: A scientific approach to care may promote weaning in difficult cases and provide directions for future research into the etiologies of weaning failure.

Furosemide, when used in combination with positive end-expiratory pressure, facilitates the resorption of extravascular lung water in experimental hydrostatic pulmonary oedema.

The study aimed to establish whether furosemide given intravenously improved resorption of hydrostatic pulmonary oedema in 14 dogs mechanically ventilated with positive end-expiratory pressure (PEEP). Hydrostatic pulmonary oedema was created by simultaneous inflation of a left atrial balloon and rapid intravenous infusion of isotonic saline. The hydrostatic process was terminated by deflating the balloon and reducing the infusion rate. A PEEP of 10 cmH2O (1.0 kPa) was applied in all animals; in seven, furosemide was administered (diuretic group), 1 mg/kg intravenously as a bolus followed by an infusion of 0.5 mg/kg per hour, while the remaining seven dogs served as a control group. All dogs were studied for a period of 4 h. The extravascular lung water measured with the double indicator dilution technique was 28.3 +/- 3.8 (diuretic group) and 28.2 +/- 6.8 ml/kg (control group) during maximum oedema. It was reduced to 16.4 +/- 2.2 (diuretic group) vs 19.8 +/- 3.7 ml/kg (control group) after 4 h of resorption, P less than 0.05. Postmortem gravimetric values of extravascular lung water were 9.1 +/- 3.4 (diuretic group) vs 12.6 +/- 5.0 g/kg (control group). In the diuretic group the urinary output increased threefold, and haemoglobin and serum protein concentrations were higher than in the control group. There was a significantly greater decrease in cardiac output and central blood volume in the diuretic group. In conclusion, furosemide given intravenously improved lung fluid resorption in hydrostatic pulmonary oedema, probably by increasing the plasma colloid osmotic pressure.

Comparative study of cell saver and ultrafiltration nontransfusion in cardiac surgery.

Hemoconcentration for the establishment of no-donor blood transfusion in open heart surgery was assessed in regard to both the saving of protein and platelets and the exclusion of free hemoglobin. Two different types of hemoconcentrator were compared: the ultrafilter (group I, 6 patients) and the Cell Saver (group II, 6 patients). The total serum protein level, expressed as the percent recovery of the preoperative value, after hemoconcentration was significantly higher in group I (group I versus group II: total serum protein, 118% versus 87% [p less than 0.05]; fibrinogen, 77% versus 50% [p less than 0.01]; immunoglobulin, 83% versus 60% [p less than 0.01]). The platelets also seemed to be well preserved after hemoconcentration in group I. Although the exclusion of free hemoglobin from plasma was inferior in group I compared with group II, the postoperative plasma free hemoglobin level did not increase in group I. We conclude that use of the Cell Saver in nontransfusion cardiopulmonary bypass might cause a severe depletion of various proteins and that the ultrafilter is both safer and more useful if employed routinely.

Acute effects of oxygen, nifedipine, and diltiazem in patients with cystic fibrosis and mild pulmonary hypertension.

The acute effects of oxygen, nifedipine, and diltiazem were studied in eight patients with cystic fibrosis and mild pulmonary hypertension, to assess the possibility of relieving the latter before the occurrence of irreversible vascular changes. Oxygen decreased pulmonary pressure (-23%) and resistance (-21%), while increasing systemic resistance (+23%). Nifedipine increased cardiac index (+30%), at the expense of augmented right ventricular work (+42%), resulting in a decreased calculated pulmonary resistance (-23%); pulmonary artery pressure remained unchanged, however. Nifedipine decreased arterial Po2 (-10%), suggesting ventilation-perfusion mismatch. Four of the eight patients responded to diltiazem. Their pulmonary pressure (-35%) and resistance (-43%) decreased, while systemic vascular tone remained unchanged. Oxygen in three patients, and diltiazem in two, returned pulmonary pressures and resistances to normal values. Early reversal of pulmonary hypertension is possible, and intervention is desirable before the establishment of chronic hypoxia, cor pulmonale, or right ventricular failure. Our data does not support the use of nifedipine in pulmonary hypertension, but shows that oxygen, and in some cases diltiazem, act as effective and selective pulmonary vasodilators.

[Effect of guided ventilation on gas exchange in kypho-scoliotic patients in post-intensive care]. / Effet de la ventilation dirigée sur les échanges gazeux du cyphoscoliotique en post-réanimation.

Post-intensive care stabilized kyphoscoliotic patients are characterized by a limited circulation which reduces VCO in relation to VCO2 (specific VCO, Sp VCO) by diminution of the "contact time". This might help in explaining the hypoxaemia observed in these patients concurrently with alveolar hypoventilation and altered ventilation/perfusion ratio. Bradypnoea (Bp) may reduce the last two factors but not the vascular field amputation. In 10 kyphoscoliotic patients examined in spontaneous ventilation (SV), then in Bp, gas exchanges were evaluated under their 2 aspects: gas flow rates and ventilatory efficiency (ERCO2, VA/V). The results obtained in 16 examinations concerning 10 patients were analysed. There were great differences in the amplitude of ventilatory response, a significant increase of VA improving PaCO2 more constantly than PaO2, a slight increase of Sp VCO and a decrease of VCO/VA. In the discussion, ERCO2 and VA/V are compared, the high VA/V and VD/VT values are justified, the uncertain effect of Bp on PaO2 is confirmed, and the relationship of Sp VCO with DuCO and PaO2 is determined. The evaluation of exchanges in SV and Bp provides information on the degree of deterioration of blood perfusion, the physiopathology of each individual subject and the advisability of kinesitherapy with Bp.

Long-term treatment with a new calcium antagonist, felodipine, in chronic obstructive lung disease.

Nine patients with advanced chronic obstructive lung disease (COLD) were treated with a calcium antagonist, felodipine, for 3-5 months and their central haemodynamics and pulmonary gas exchange were then studied. The systemic vascular resistance was reduced by 19% (p less than 0.05) at rest and by 30% during ergometer bicycle exercise (p = 0.05) compared to pretreatment data, whereas pulmonary vascular resistance showed a borderline reduction of 10% at rest and 30% during exercise (p = 0.12 and p = 0.10, respectively). Stroke volume increased by 13% (p less than 0.05) at rest and to the same extent at exercise. A moderate deterioration of the ventilation-perfusion relationship was seen by the multiple inert gas elimination technique, and the arterial oxygen tension was further reduced by 3.5 mmHg (p less than 0.05) at rest and by 3.0 mmHg on exercise, but the working capacity on an ergometer bicycle increased from 60 to 70 W (p less than 0.01). No acceptable predictor of patients who would respond to the drug could be found.