Plasma cyclic guanosine 3'-5' monophosphate concentrations and low vascular resistance in human septic shock.

OBJECTIVE: To investigate the increase in plasma cyclic GMP (cGMP) concentrations in humans with hyperkinetic septic shock (SS) and to evaluate its relationship to low systemic vascular resistance (SVR). DESIGN: Prospective clinical investigation. SETTING: Medical intensive care unit of a university hospital. PATIENTS: 22 patients with documented SS requiring hemodynamic resuscitation, respiratory support and--in some cases--hemodialysis. MEASUREMENTS AND RESULTS: Hemodynamic data were recorded at admission time and then twice a-day during the following 72 h. We simultaneously measured cyclic GMP, atrial natriuretic peptides (ANP), creatininemia and platelet counts. At admission time, higher plasma cGMP concentrations were observed in patients with SS (11.84 +/- 1.52 pmol.ml-1) than in healthy controls (1.77 +/- 0.18 pmol.ml-1, p < 0.0001), in septicemia patients without circulatory failure (3.28 +/- 0.36 pmol.ml-1, p < 0.005) or in patients with hyperkinetic non-septic shock (3.6 +/- 0.7 pmol.ml-1, p < 0.02). In contrast, there was no significant difference between patients with SS and controls with anuria from non-septic origin. Also ANP concentrations were higher in patients with SS than in others. In addition, cGMP levels correlated negatively with SVR during the first 48 h of the study, and positively with creatininemia later when renal function worsened. However, they did not correlate significantly with ANP. CONCLUSION: These data demonstrate that a significant increase in plasma cGMP concentrations occurs during human SS and that it correlates with the decline in peripheral vascular resistance in the absence, but not in the presence, of severe renal failure. Furthermore, the increase in cGMP levels cannot be ascribed solely to enhanced ANP-induced particulate guanylyl cyclase activity. Thus, our results suggest the occurrence of another endogenous source of cGMP during hyperkinetic SS.

Neurological complications and pleural lavage with a fibrinolytic agent. A two-case report.

We report on an unusual, albeit potentially severe, complication of the performance of a pleural lavage with streptokinase in two patients demonstrating parapneumonic pleural effusion. During the time they underwent repeated pleural lavages with saline and streptokinase, they suddenly demonstrated focal neurological signs. As a result of early diagnosis and emergency hyperbaric oxygenation, both patients recovered without delayed sequelae. Air embolism is a potentially severe complication which can occur during pleural lavage. Whether streptokinase increases the risk of opening a latent vascular breach cannot be definitely established, but clinicians should be aware of this risk. In this context, the onset of acute focal neurological signs should suggest the possibility of air embolism and lead to the transfer of the patient close to a hyperbaric facility within a few hours.

Acute interstitial pulmonary fibrosis. Comparative light and electron microscopic study of 19 cases. Pathogenic and therapeutic implications.

Comparative light and electron microscopic studies of the lung were performed in 19 cases of diffuse acute interstitial fibrosis with various etiologies. Our observations emphasize the relation between hyaline membranes (HM) and the evolution of fibrosis. HM formation is due to fibrinous exudates and epithelial necrosis. This phenomenon recurs during the evolution of the disease and appears to be responsible for new waves of fibrosis. Its pathogenesis (humoral or neurovascular ...) remains hypothetical. Modifications of the alveolar epithelium consecutive to septal fibrosis can be clearly distinguished from "fibrinoid necrosis" -type lesions, which results in HM. The formation of HM is accompanied by fibroblastic stimulation which proceeds in spite of epithelial regeneration. The exact stimulus for the proliferation and collagen hypersecretion of fibroblasts remains to be determined. The use, in association with corticosteroid treatment, of a structural analogue of L lysine, acexamic acid, to impede collagenesis reveals encouraging perspectives for improved therapy.

Methylene blue increases systemic vascular resistance in human septic shock. Preliminary observations.

We report the hemodynamic improvements induced by intravenous methylene blue (MB), a guanylate cyclase inhibitor, in 2 patients with hyperdynamic septic shock treated with norepinephrine (NE) infusion, mechanical ventilation and hemodialysis. MB injection augmented the low vascular resistance, mean arterial pressure and induced a slight decrease of cardiac index, without any change of heart rate and pulmonary artery wedge pressure. Plasma cyclic GMP levels decreased without a significant change of atrial natriuretic factor levels. MB (2 mg.kg-1) induced a longer lasting improvement of circulatory failure without deleterious side effects, but did not prevent the occurrence of delayed multiorgan failure or subsequent death. These data suggest that in patients, severe sepsis-induced loss of vascular responsiveness to NE involves activation of soluble guanylate cyclase, possibly stimulated by enhanced nitric oxide production. Furthermore, these observations support the concept that pharmacological blockade of guanylate cyclase may improve hemodynamics but not survival rates.

[Auditory P300 in subjects in a post-anoxic coma. Preliminary data]. / Etude du P300 auditif chez des sujets en coma post-anoxique. Données préliminaires.

The first results concerning the role of event related potentials (P300) in assessing a prognosis in comatose patients reported in the literature have been encouraging. The cause of the coma is an important prognostic factor by itself, especially when traumatic and anoxic comas are compared, with a less favorable prognosis in anoxic coma. In our study, only anoxic patients have been investigated using somatosensory evoked potentials, brainstem auditory evoked potentials P300 auditory event-related potentials. Clinical evaluation was performed using Glasgow, Liege and Jouvet coma scales. In twenty patients studied, six had a positive P300 and three of them awake. Out of the 14 patients without a P300 only one awoke (5%), 12 patients died and one is in deep coma. Despite the small number of patients in this study, the first results confirm the interest of auditory P300, in addition to clinical evaluation and evoked potential testing.

[Hyperosmolar comatose states]. / Gli stati comatosi iperosmolari

A recently determined entity, hyperosmolar coma is a good example of a clinical candition attributable to a fundamental alteration, namely extracellular hyperosmolarity. The principal stages in its history are summarised. The laws governing osmosis are recalled and the various features of the sndrome are studied. Attention is drawn to the clinical peculiarities (skin dehydration), biological features (record glycaemia value), and EEG data noted in 17 cases treated in a resuscitation centre over a period of seven years, along with the treatment employed-this being still a matter of debate. Reference is also made to 52 cases of acute drunkenness in a study of the relation between blood alcohol values and plasma hyperosmolarity.

[Role of hygiene and bacteriological laboratories in the management of an epidemic of Enterobacter aerogenes multiresistant to antibiotics]. / Rôles des laboratoires d'hygiène et de bactériologie dans la prise en charge d'une épidémie à Enterobacter aerogenes multirésistant aux antibiotiques.

We describe a multiresistant Enterobacter aerogenes outbreak in an intensive care-unit. An epidemiology study based on phenotypic characters (species diagnosis and antibiotype) was completed by a genotypic study (pulsed field electrophoresis) to confirm bacterial clonality. The hygiene laboratory proposed numerous preventive measures to limit bacterial dispersion. We describe the role of bacteriologists, hygienists and medical staff to stop the bacterial dispersion.

[Wound healing and hyperbaric oxygen. Experimental study of the angiogenesis phase in the rat]. / La cicatrisation sous oxygénothérapie hyperbare. Etude expérimentale de sa phase angiogénique chez le rat.

Hyperbaric oxygen therapy (HBO) is widely reported as highly favourable to wound healing. The experimental models generally used to investigate its effects are difficult to set up and reliable quantification of the results obtained is rarely achieved. The underlying pathophysiological mechanisms occurring during HBO remain poorly understood and its mode of application for clinical practice is difficult to standardise. Our study was carried out to assess the contributions of oxygen and hyperbaric pressure on the initial steps of wound healing. It was based on qualitative and quantitative analysis of the development of the angiogenic process in a granulation tissue bud, using animals implanted with fibrin chambers, an in vivo model initially described by Dvorak in guinea pigs. In our study, rats were further submitted to HBO (OHB group) or hyperbaric air (Air-HB group) treatments. The control group (Control group) consisted of rats maintained in the treatment tank under normal atmospheric conditions. Nine specific parameters were determined and analysed during the course of the angiogenic process by classical histological techniques. The vascular density and the height of the bud were particularly examined at day 7, 14 and 21 following chamber implantation. At D7 the neovessel density and bud height were significantly higher in OHB group than in Air-HB or Control groups, thus confirming the beneficial effects of this treatment on the initial steps of wound healing. Nevertheless, the results reported herein also suggest a possible inhibitory effect of hyperbaric therapy alone on this very early process, although the pathophysiological significance of this effect on wound healing remains to be determined.

[Acute post-operative peritonitis in gastro-enterological surgery. Opinion of the intensive care unit (author's transl)]. / Les péritonites post-opératoires après chirurgie digestive. Le point de vue du réanimateur.

Acute purulent post-operative peritonitis is highly severe and difficult to diagnose. Six symptoms have a real prognostic value: shock, acute renal insufficiency, respiratory failure, jaundice, acidosis and septicaemia. If more than three of these signs of severity coexist, the mortality rate reaches nearly 100%. A patient with evidence of acute diffuse post-operative peritonitis must be operated on after a short preoperative treatment to restore a situation altered by shock, renal failure and pulmonary edema. Antibiotic agent alone, though necessary, cannot bring recovery. The maintenance of high nutritional intake for excess caloric expenditure is essential. The effects of the early decision of a surgical reintervention are studied in 27 patients with only two recoveries.

[Prognostic factors of decompensated chronic respiratory insufficiency. Apropos of a series of 272 cases]. / Facteurs pronostiques des insuffisances respiratoires chroniques décompensées. A propos d'une série de 272 observations.

Over a 6 years' period (1980-1986), 272 patients with chronic respiratory disease were admitted for respiratory failure to the same intensive care unit. The series was characterized by the high mean age of the patients (69.3 years) and by the high proportion of those who were ventilated (75%); 33.7% of the patients died within 1 month of discharge. The survival rate at 5 years estimated by the actuarial survival curve was 28%. Parameters measured during the acute decompensation phase were analyzed statistically. The main prognostic factors regarded as unfavourable were: old age and associated visceral failure particularly, important loss of weight and muscular atrophy, pre-existing neurological sequelae, left ventricular dysfunction, simplified Le Gall score above 15, presence of respiratory encephalopathy, stroke or viral infection as precipitating factors of decompensation, transfer from other hospital units after failure of medical treatment, and need for mechanical ventilation for more than 30 days.

[Vital capacity restitution curve: prognostic value in chronic decompensated respiratory insufficiency]. / La courbe de restitution de la capacité vitale: intérêt pronostique au cours des insuffisances respiratoires chroniques décompensées.

From a series of 50 patients with acute decompensation of chronic obstructive lung disease (38 of whom were treated by mechanical ventilation), the authors demonstrate the prognostic value of an easily obtained parameter of respiratory function: the vital capacity restitution curve (VCRC). From daily measurements of vital capacity, beginning on the day of admission, a graph is constructed which shows an initial period of increase in the degree of restitution, followed by stabilization of the values. An analysis of the various parameters embodied in this graph provides information about the prognosis. Such graphs can be divided into 3 zones of prognostic value: a favourable zone, an intermediate zone (mediocre survival with or without mechanical ventilation) and an unfavourable zone (death during the acute phase). Although a favourable prognosis can be made after 4 days of observation and almost always by the 10th day, an unfavourable prognosis cannot be made before the 21st day.

[Developmental modalities of septic states. Multiple organ failure syndrome]. / Modalités évolutives des états septiques. Le syndrome de défaillance multiviscérale.

Sepsis syndrome occurs when an acute infection results in an host generalized inflammatory response including cytokines production. Death is a frequent and unpredictable sequel of this pathological condition. It may be due either to uncontrolled circulatory failure, or to multiple organ failure. With the advent of nitric oxide in the arena of the most potent vasodilatator agents, we now better understand the mechanisms of low vascular resistance during hyperkinetic septic shock. However a closer understanding of the mechanisms of multiple organ failure is actually required to improve survival rates during severe human sepsis.