Jean Claude Raphael

Circulating vasopressin levels in septic shock

OBJECTIVE To assess the frequency of vasopressin deficiency in septic shock. DESIGN Prospective cohort study. SETTING Intensive care unit at Raymond Poincaré University Hospital. PATIENTS A cohort of 44 patients who met the usual criteria for septic shock for < 7 days. A second cohort of 18 septic shock patients were enrolled within the first 8 hrs of disease onset. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS General demographics, severity scores, vital signs, standard biochemical data, and circulating vasopressin levels were systematically obtained at baseline in the two cohorts. Vasopressin deficiency was defined by a normal plasma vasopressin level in the presence of a systolic blood pressure of <100 mm Hg or in the presence of hypernatremia. Baroreflex sensitivity was systematically evaluated in patients of the first cohort when vasopressin deficiency was noted. In the second cohort of patients, plasma levels of vasopressin were obtained at baseline, 6, 24, 48, and 96 hrs after shock onset. In the first population, plasma vasopressin levels were inversely correlated to the delay from shock onset. Fourteen patients had relative vasopressin deficiency: 12 patients had systolic blood pressure <100 mm Hg, with impaired baroreflex sensitivity in four, and three patients had hypernatremia. In the second population, only two patients had relative vasopressin deficiency. The plasma levels of vasopressin significantly decreased over time (p < 10-3). CONCLUSIONS Plasma vasopressin levels are almost always increased at the initial phase of septic shock and decrease afterward. Relative vasopressin deficiency is seen in approximately one-third of late septic shock patients.

Compartmentalised inducible nitric-oxide synthase activity in septic shock

BACKGROUND Previous experimental studies support a role for inducible nitric-oxide synthase (iNOS) in the pathogenesis of severe sepsis. The aim of the study was to characterise iNOS activity in different tissues in patients with septic shock. METHODS 13 consecutive patients with septic shock caused by cellulitis were enrolled. Skin, muscle, fat, and artery samples were obtained from normal, inflamed, and putrescent areas to measure iNOS activity, and concentrations of tumour necrosis factor alpha (TNFalpha) and interleukin 1beta (IL-1beta). In two patients, iNOS activity was also assessed in peripheral blood mononuclear cells (PBMC) incubated with microorganisms causing the sepsis, or in macrophages isolated from suppurating peritoneal fluid incubated with IL-1beta. FINDINGS Compared with normal and inflamed areas, iNOS activity was increased in putrescent areas for muscle (71-fold [95% CI 20-259] vs normal areas, 69-fold [19-246] vs inflamed areas; p<0.01 for each) and for fat (68-fold [23-199] and 49-fold [18-137], respectively; p<0.01), but not for skin. Compared with normal areas, putrescent areas of arteries showed increased iNOS expression (1280-fold [598-3153]; p<0.01). Compared with normal areas, TNFalpha and IL-1beta were increased in putrescent areas of arteries (223-fold and 41-fold, respectively; p<0.01 for each). PBMCs and tissue macrophages expressed iNOS. Plasma nitrite/nitrate concentrations inversely correlated with mean arterial pressure and systemic vascular resistance. INTERPRETATION In human septic shock we found that iNOS activity is compartmentalised at the very site of infection and parallels expression of TNFalpha and IL-1beta. PBMCs and tissue macrophages can be a cellular source for iNOS.

Sleep-related respiratory disturbances in patients with Duchenne muscular dystrophy.

Sleep-related respiratory disturbances (SRD) in patients with muscle diseases may have significant clinical implications, because the patients frequently die at night. The aims of the study were to :1) assess the presence and severity of sleep-related respiratory disturbances in patients with Duchenne muscular distrophy (DMD); and 2) investigate the relationship of sleep-related respiratory disturbances to daytime symptoms and pulmonary function. We studied six clinically stable patients with Duchenne muscular dystrophy, mean age (+/- SD) 18 +/- 2 yrs. Vital capacity was 27 +/- 19% of predicted and daytime arterial oxygen tension (PaO2) was 10.9 +/- 1 kPa (range 8.9-12.4 kPa). The presence of daytime somnolence, insomnia, headache, nightmares and/or snoring was recorded. Four patients (67%) showed symptoms that suggest sleep-related respiratory disturbances. At night, the apnoea-hypopnoea index (AHI) was 11 +/- 6. The patients with more symptoms during the daytime had the highest AHI scores. Most of the apnoeas (85%) were central, particularly during rapid eye movement (REM) sleep. Sleep architecture was well-preserved. Arterial desaturation (> 5% below baseline) occurred during 25 +/- 23% of total time. AHI correlated with daytime PaO2, and AHI in REM sleep correlated with age. A stepwise multivariate analysis showed that PaO2 and, to some extent, the degree of airflow obstruction were significantly correlated with AHI. We conclude that sleep-related respiratory disturbance are frequently present in patients with Duchenne muscular dystrophy. Therefore, physicians should look for symptoms related to sleep-related respiratory disturbances in these patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Cough determinants in patients with neuromuscular disease

Neuromuscular disease leads to cough impairment. Cough augmentation can be achieved by mechanical insufflation (MI) or manually assisted coughing (MAC). Many studies have compared these two methods, but few have evaluated them in combination. In 155 neuromuscular patients, we assessed determinants of peak cough flow (PCF) using stepwise correlation. Maximal inspiratory capacity contributed 44% of the variance (p<0.001), expiratory reserve volume 13%, and maximal expiratory pressure 2%. Thus, augmenting inspiration seems crucial. However, parameters dependent on expiratory muscles independently influence PCF. We measured vital capacity and PCF in 10 neuromuscular patients during cough augmentation by MI, MAC, or both. MI or MAC significantly improved VC and PCF (p<0.01) as compared to the basal condition and VC and PCF were higher during MI plus MAC than during MAC or MI alone (p<0.01). In conclusion, combining MAC and MI is useful for improving cough in neuromuscular patients.

Respiratory insufficiency and limb muscle weakness in adults with Pompe’s disease

The objective of the present study was to prospectively evaluate relationships linking age, respiratory function and locomotor function in 29 outpatients with late-onset Pompe’s disease and to retrospectively determine clinical outcomes. Using univariate regression analysis, vital capacity (VC) was weakly, but significantly, correlated to shoulder motility, Walton score and lower-limb Modified Medical Research Council score. Six patients were able to walk without a walking aid and with only the help of a handrail on the stairs (Walton score = 3), although VC was <50%. No parameters were significantly correlated with age. As assessed retrospectively, VC and locomotion deteriorated over time in most patients. In contrast, among the 16 patients started on invasive or noninvasive ventilation with VC monitoring, eight had a VC increase at the first measurement time-point. The absence of correlation with age and the presence, in some patients, of severe respiratory insufficiency without severe limb girdle muscle weakness indicate that respiratory function should be monitored independently from the degree of peripheral muscle weakness. Mechanical ventilation and tracheostomy may improve vital capacity and should, therefore, be taken into account when evaluating treatments for the adult form of Pompe’s disease.

Acute carbon monoxide intoxication and hyperbaric oxygen in pregnancy

Modalities of oxygen therapy for pregnant women intoxicated with carbon monoxide (CO) are ill defined. Hyperbaric oxygen (HBO) is presumed to be hazardous to the pregnancy. On the other hand CO entails anoxic injuries in the mother and fetus. We have entered 44 pregnant women who sustained an acute carbon monoxide poisoning at home, into a prospective study in order to assess HBO tolerance. They were treated within 5.3±3.7 h (range: 1–12) of the intoxication with a combination of 2 h of HBO at a pressure of 2 atmospheres absolute (ATA) and 4 h of normobaric oxygen, irrespective of the clinical severity of the intoxication and of the age of pregnancy. Six patients were lost to obstetric follow-up. Only 2 patients sustained a spontaneous abortion: 1 within 12 h and 1 within 15 days of the intoxication. Thirty-four women gave birth to normal newborns. Finally 1 elected to undergo abortion for reasons unrelated to the intoxication and 1 gave birth to a baby with Downs syndrome. There is no evidence that HBO was involved with either abortion of our study. We conclude that HBO may be carried out in pregnant women acutely intoxicated with carbon monoxide.

High-Dose Intravenous Gamma Globulin For Myasthenia Gravis: An Alternative to Plasma Exchange?

In 1981 Imbach et al. reported good results in the treatment of idiopathic thrombocytopenic purpura with high-dose intravenous gamma globulins. Since then, this treatment has been proposed in other autoimmune disorders with various outcomes. In a previous study we observed a beneficial effect with high-dose intravenous IgG in five myasthenic patients? We report here results with this treatment in 21 patients.

Respiratory dysfunction in Guillain-Barré Syndrome.

Guillain-Barré Syndrome is the leading cause of nontraumatic acute paralysis in industrialized countries. About 30% of patients have respiratory failure requiring intensive care unit (ICU) admission and invasive mechanical ventilation. Progressive weakness of both the inspiratory and the expiratory muscles is the mechanism leading to respiratory failure. Aspiration pneumonia and atelectasis are common consequences of the bulbar muscle weakness and ineffective cough. The classical signs of respiratory distress occur too late to serve as guidelines for management, and measurements of vital capacity and static respiratory pressures are useful to determine the best times for starting and stopping mechanical ventilation. Several factors present at admission and during the ICU stay are known to predict a need for invasive mechanical ventilation. They include rapidly progressive motor weakness, involvement of both the peripheral limb and the axial muscles, ineffective cough, bulbar muscle weakness, and a rapid decrease in vital capacity. Specific treatments (plasma exchange and intravenous immunoglobulins) have decreased both the number of patients requiring ventilation and the duration of ventilation. The need for mechanical ventilation is associated with residual functional impairments, although all patients eventually recover normal respiratory muscle function.

Effects of mechanical ventilation with normobaric oxygen therapy on the rate of air removal from cerebral arteries

ObjectiveWe conducted the current study to evaluate the removal rate of air embolism from cerebral arteries after spontaneous breathing at a low FIO2 in comparison with mechanical ventilation at an FIO2 of 1.0. DesignRandomized, experimental trial. SettingNeuroimaging department at a veterinary school hospital laboratory. SubjectsNine anesthetized beagles undergoing mechanical ventilation with previous normal cranial computed tomography (CT) scan. InterventionsIn each dog, after a control scan, air was infused at a constant flow rate, via a catheter inserted into the internal carotid artery. CT scan was repeated until typical bubbles appeared. Immediately after, the animals were randomly assigned to breathe room air (group A), or to be mechanically ventilated at an FIO2 of 1.0 (group B). CT scan was again repeated every minute until the removal of all bubbles. We compared the volume of air infused per kg of body and brain weights, the lowest density among bubbles (Hounsfield units), the duration of radiologic findings, and the ratio of volume/duration (mL/kg/min) between the two groups, using the Mann-Whitney test. ResultsThe volume of air infused per kg of body and brain weights and density were not significantly different between the two groups. The duration of radiologic findings was shorter (p < .02) in group B (7.0 ± 4.7) than in group A (20.4 ± 3.8), and the air removal rate from cerebral arteries (expressed as volume/duration of radiologic findings) was dramatically improved (p < .02) in group B (0.159 ± 0.042) in comparison with group A (0.046 ± 0.016). ConclusionsThese results suggest that the removal rate of air from cerebral arteries is dramatically increased by mechanical ventilation at an FIO2 of 1.0. Consequently, the time of cerebral ischemia may be decreased, but the result does not account for the effects of each factor separately. Further studies are required to evaluate the clinical benefits of high FIO2 administration and of mechanical ventilation separately. However, the prompt application of mechanical ventilation with an FIO2 of 1.0 may be recommended when air embolism is suspected. (Crit Care Med 1994; 22:851–857)

Assessing inspiratory muscle strength by sniff nasal inspiratory pressure

The sniff nasal inspiratory pressure (SNIP) consists in the measurement of pressure through an occluded nostril during sniffs performed through the controlateral nostril. It is an accurate and noninvasive approximation of esophageal pressure swing during sniff maneuvers. HoweverSNIP can underestimate esophageal pressure swing in subjects with nasal obstruction, patients with chronic obstructive pulmonary disease and severe neuromuscular patients. Nevertheless, since SNIP maneuver has predicted normal values, is noninvasive and is easier to perform than maximal inspiratory pressure (MIP) maneuver, it could be considered as the first simple test to use in order to assess inspiratory muscle weakness. In addition, because it is as reproducible as MIP, it can be suitable to follow inspiratory muscle function in chronic neuromuscular patients. Because, of the important limit of agreement between SNIP and MIP, these two methods are not interchangeable but complementary.