Respiratory mechanics and gas exchanges in the early course of COVID-19 ARDS: a hypothesis-generating study.

RATIONALE: COVID-19 ARDS could differ from typical forms of the syndrome. OBJECTIVE: Pulmonary microvascular injury and thrombosis are increasingly reported as constitutive features of COVID-19 respiratory failure. Our aim was to study pulmonary mechanics and gas exchanges in COVID-2019 ARDS patients studied early after initiating protective invasive mechanical ventilation, seeking after corresponding pathophysiological and biological characteristics. METHODS: Between March 22 and March 30, 2020 respiratory mechanics, gas exchanges, circulating endothelial cells (CEC) as markers of endothelial damage, and D-dimers were studied in 22 moderate-to-severe COVID-19 ARDS patients, 1 [1-4] day after intubation (median [IQR]). MEASUREMENTS AND MAIN RESULTS: Thirteen moderate and 9 severe COVID-19 ARDS patients were studied after initiation of high PEEP protective mechanical ventilation. We observed moderately decreased respiratory system compliance: 39.5 [33.1-44.7] mL/cmH2O and end-expiratory lung volume: 2100 [1721-2434] mL. Gas exchanges were characterized by hypercapnia 55 [44-62] mmHg, high physiological dead-space (VD/VT): 75 [69-85.5] % and ventilatory ratio (VR): 2.9 [2.2-3.4]. VD/VT and VR were significantly correlated: r2 = 0.24, p = 0.014. No pulmonary embolism was suspected at the time of measurements. CECs and D-dimers were elevated as compared to normal values: 24 [12-46] cells per mL and 1483 [999-2217] ng/mL, respectively. CONCLUSIONS: We observed early in the course of COVID-19 ARDS high VD/VT in association with biological markers of endothelial damage and thrombosis. High VD/VT can be explained by high PEEP settings and added instrumental dead space, with a possible associated role of COVID-19-triggered pulmonary microvascular endothelial damage and microthrombotic process.

Runoff initiation, soil detachment and connectivity are enhanced as a consequence of vineyards plantations.

Rainfall-induced soil erosion is a major threat, especially in agricultural soils. In the Mediterranean belt, vineyards are affected by high soil loss rates, leading to land degradation. Plantation of new vines is carried out after deep ploughing, use of heavy machinery, wheel traffic, and trampling. Those works result in soil physical properties changes and contribute to enhanced runoff rates and increased soil erosion rates. The objective of this paper is to assess the impact of the plantation of vineyards on soil hydrological and erosional response under low frequency - high magnitude rainfall events, the ones that under the Mediterranean climatic conditions trigger extreme soil erosion rates. We determined time to ponding, Tp; time to runoff, Tr; time to runoff outlet, Tro; runoff rate, and soil loss under simulated rainfall (55 mm h-1, 1 h) at plot scale (0.25 m2) to characterize the runoff initiation and sediment detachment. In recent vine plantations (<1 year since plantation; R) compared to old ones (>50 years; O). Slope gradient, rock fragment cover, soil surface roughness, bulk density, soil organic matter content, soil water content and plant cover were determined. Plantation of new vineyards largely impacted runoff rates and soil erosion risk at plot scale in the short term. Tp, Tr and Tro were much shorter in R plots. Tr-Tp and Tro-Tr periods were used as connectivity indexes of water flow, and decreased to 77.5 and 33.2% in R plots compared to O plots. Runoff coefficients increased significantly from O (42.94%) to R plots (71.92%) and soil losses were approximately one order of magnitude lower (1.8 and 12.6 Mg ha-1 h-1 for O and R plots respectively). Soil surface roughness and bulk density are two key factors that determine the increase in connectivity of flows and sediments in recently planted vineyards. Our results confirm that plantation of new vineyards strongly contributes to runoff initiation and sediment detachment, and those findings confirms that soil erosion control strategies should be applied immediately after or during the plantation of vines.

Comparison of intensive-care-unit-acquired infections and their outcomes among patients over and under 80 years of age.

BACKGROUND: Patients aged >80 years represent a growing population admitted to intensive care units (ICUs). However, little is known about ICU-acquired infection (IAI) in this population, and the rate of invasive procedures is increasing. AIM: To evaluate the frequency and effects of IAI in elderly (≥80 years) and younger patients. METHODS: Retrospective evaluation of consecutive patients hospitalized for three days or more over a three-year period in an 18-bed ICU in an academic medical centre. FINDINGS: Elderly patients represented 18.9% of the study population. At admission, the mean number of organ dysfunctions was similar in elderly and younger patients. The use of invasive procedures was also similar in elderly and younger patients, as follows: invasive mechanical ventilation for more than two days, 67.4% vs 55%; central venous catheterization, 56.9% vs 51.4%; and renal replacement therapy, 17.6% vs 17.8%, respectively. The frequency of IAI was 16.5% in elderly patients and 13.9% in younger patients (P = 0.28), with 20.5 vs 18.9 IAI episodes per 1000 ICU-days, respectively (P = 0.2). A Cox model identified central venous catheterization and invasive mechanical ventilation for more than two days as independent risk factors for IAI. The associations between IAI and prolonged ICU stay, increased nursing workload, and ICU and hospital mortality rates were similar in elderly and younger patients. CONCLUSIONS: The frequency of IAI was similar in elderly and younger patients, as were the associations between IAI and length of ICU stay, nursing workload and ICU mortality in an ICU with a high rate of invasive procedures.

[Acute respiratory distress syndrome due to Toxocara cati infection]. / Syndrome de détresse respiratoire aiguë secondaire à une infection à Toxocara cati.

Human toxocarosis is a helminthozoonosis due to the migration of toxocara species larvae throughout the human body. Lung manifestations vary and range from asymptomatic infection to severe disease. Dry cough and chest discomfort are the most common respiratory symptoms. Clinical manifestations include a transient form of Loeffler's syndrome or an eosinophilic pneumonia. We report a case of bilateral pneumonia in an 80 year old caucasian man who developed very rapidly an acute respiratory distress syndrome, with a PaO2/FiO2 ratio of 55, requiring mechanical ventilation and adrenergic support. There was an increased eosinophilia in both blood and bronchoalveolar lavage fluid. Positive toxocara serology and the clinical picture confirmed the diagnosis of the "visceral larva migrans" syndrome. Intravenous corticosteroid therapy produced a rapid rise in PaO2/FiO2 before the administration of specific treatment. A few cases of acute pneumonia requiring mechanical ventilation due to toxocara have been published but this is, to our knowledge, is the first reported case of ARDS with multi-organ failure.

Differential and irreversible CNS ontogenic reduction in maximal MK-801 binding site number in the NMDA receptor after acute hypoxic hypoxia.

CNS exposure to hypoxia impairs excitatory and inhibitory neurotransmission. Our aim was to determine variations induced by normobaric acute hypoxic hypoxia (8% O(2) for 60 min) on the NMDA receptor complex, as well as their potential reversibility after normoxic recovery. To this end, [3H]MK-801 binding assays to a synaptic membrane fraction isolated from chick optic lobes were performed. Previous studies throughout development had disclosed a characteristic age-dependent pattern. Results at embryonic day (ED) 12 and 18 indicated two distinct MK-801 binding sites. Hypoxic treatment failed to alter either the high affinity site dissociation constant (K(d)) or its maximal binding capacity (B(max)), whereas the low affinity site B(max) was significantly decreased (50% and 30% at ED12 and 18, respectively), without alteration in its K(d) values. Hypoxic embryos restored for 48 h at ED12 to normoxic conditions displayed unchanged MK-801 binding reduction, unlike those treated likewise at ED18 whose values fully recovered control levels. To conclude, hypoxic treatment reduces low affinity MK-801 B(max) in the NMDA receptor which proves irreversible up to ED12. Such early neuronal vulnerability may be due to post-transcriptional changes, to endocytosis followed by receptor degradation, or alternatively to cell death.

Acute hypoxic hypoxia alters GABA(A) receptor modulation by allopregnanolone and pentobarbital in embryonic chick optic lobe.

Using a previously developed model of acute normobaric hypoxic hypoxia on chick embryos, here we studied at embryonic day 12 the in vitro effect of two positive allosteric modulators of GABA binding, the barbiturate sodium pentobarbital and the neurosteroid allopregnanolone. In both cases an increase in E(max) values in membranes obtained from hypoxic embryos was observed. Studies of GABA-gated chloride influx showed that there were no differences in maximal chloride uptake between hypoxic and control membranes. We have already demonstrated that maximal density of GABA binding sites was decreased after hypoxia, suggesting that each of the remaining GABA(A) receptors display a greater chloride flux than controls. To further characterize GABA(A) receptor alterations, GABA-gated chloride influx modulated by the above barbiturate and neurosteroid was determined, finding that E(max) values were increased 60% and 42%, respectively. The increase in Cl(-) influx per receptor subsequent to hypoxic trauma, and the enhancement in the modulatory properties studied, may mediate neuronal damage by potential changes in subunit interaction at the GABA(A) receptor level.

Prolonged exposure to hypobaric hypoxia transiently reduces GABA(A) receptor number in mice cerebral cortex.

The central nervous system is severely affected by hypoxic conditions, which produce alterations in neural cytoarchitecture and neurotransmission, resulting in a variety of neuropathological conditions such as convulsive states, neurobehavioral impairment and motor CNS alterations. Some of the neuropathologies observed in hypobaric hypoxia, corresponding to high altitude conditions, have been correlated with a loss of balance between excitatory and inhibitory neurotransmission, produced by alterations in glutamatergic and GABAergic receptors. In the present work, we have studied the effect of chronic hypobaric hypoxia (506 hPa, 18 h/day x 21 days) applied to adult male mice on GABA(A) receptors from cerebral cortex, to determine whether hypoxic exposure may irreversibly affect central inhibitory neurotransmission. Saturation curves for [3H]GABA specifically bound to GABA(A) receptors in isolated synaptic membranes showed a 30% decrease in maximal binding capacity after hypoxic exposure (Bmax control, 4.70+/-0.19, hypoxic, 3.33+/-0.10 pmol/mg protein), with no effect on GABA binding sites affinity (Kd control: 159.3+/-13.3 nM, hypoxic: 164.2+/-15.1 nM). Decreased B(max) values were observed up to the 10th post-hypoxic day, returning to control values by the 15th post-hypoxic day. Pharmacological properties of GABA(A) receptor were also affected by hypoxic exposure, with a 45 to 51% increase in the maximal effect by positive allosteric modulators (pentobarbital and 5alpha-pregnan-3alpha-ol-20-one). We conclude that long-term hypoxia produces a significant but reversible reduction on GABA binding to GABA(A) receptor sites in cerebral cortex, which may reflect an adaptive response to this sustained pathophysiological state.

Autoantibodies against platelet glycoproteins in critically ill patients with thrombocytopenia.

PURPOSE: The aim of the study was to investigate immunologic causes of thrombocytopenia in critically ill patients, especially causes that were related to platelet-associated IgG antibodies. SUBJECTS AND METHODS: All patients admitted to two intensive care units between May 1 and October 30, 1997, who developed thrombocytopenia (less than 100 x 10(9) platelets/L) were studied prospectively. We measured platelet-associated IgG with a radioimmunoassay using I(125)-labeled polyclonal antihuman IgG. Characterization of platelet-associated IgG was assessed with a monoclonal antibody immobilization of platelet antigen. Circulating immune complexes were also assayed. RESULTS: Of the 61 patients with thrombocytopenia, elevated platelet-associated IgG was found in 18 (30%). Associated antiplatelet autoantibodies (glycoprotein IIb/IIIa) were detected in 4 patients, circulating autoantibodies (glycoprotein Ib/IX) were detected in sera from 2 patients, and circulating immune complexes were detected in 3 patients. The nature of the platelet-associated IgG could not be determined in 10 patients. Elevated platelet-associated IgG was associated with sepsis and previous cardiopulmonary bypass. Thrombocytopenic patients with elevated platelet-associated IgG had a lower nadir platelet count (58 +/- 27 x 10(9)/L vs 74 +/- 24 x 10(9)/L, P = 0.03). CONCLUSION: Elevated platelet-associated IgG, some of which are platelet autoantibodies, is frequent in thrombocytopenic patients with sepsis or after cardiopulmonary bypass.

Synaptic membrane freezing affects modulatory sites in avian central nervous system GABA(A) receptor.

Studies were carried out to determine whether barbiturates and neurosteroids share common recognition sites at the GABA(A) receptor complex in avian CNS. To achieve this, differentially prepared fresh and frozen synaptic membranes were used. Both the barbiturate, pentobarbital, and the neurosteroid, 3alpha-hydroxy-5alpha-pregnan-20-one, were able to stimulate GABA binding in both types of membranes. Stimulation differed markedly when both drugs were added jointly to different treated tissue. In frozen membranes drugs acted synergistically and were differentially displaced by picrotoxinin, while in fresh ones, where both compounds were inhibited by the convulsant, this additivity was absent. Post-freezing wash supernatants were collected and used as a source of putative endogenous factors involved in the above mentioned membrane differences. Addition of a high molecular weight fraction from supernatants to frozen synaptic membranes led to an inhibition of barbiturate and neurosteroid potentiation, as well as a loss of their additive effect. Our results indicate that GABA(A) receptor modulation by barbiturates and neurosteroids is affected by synaptic membrane treatment, with a common modulatory site in fresh membranes and separate recognition sites after a freeze-thawing procedure. There may also be endogenous factors involved in overlapping of modulatory sites, which would thus regulate GABA(A) receptor functionality by direct interaction with the complex.

Modulatory action of zinc on GABA(A) receptor complex during avian CNS development.

In the present work, we studied the effect of zinc on GABA(A) receptor complex at three developmental stages of chick optic lobe (embryonic day 14, post-hatching day 1, and adulthood), in order to investigate the role of this cation in central nervous system (CNS) functional maturation. It was demonstrated that zinc exerts an inhibitory modulation of both GABA binding and GABA-gated chloride flux in a concentration-dependent manner with maximal effects at 100 microM zinc concentration. Maximal inhibition was higher at the embryonic stage and declined thereafter, disclosing minimal values at the adult stage. The effect of zinc on saturation GABA binding experiments performed at embryonic day 14 demonstrated that the cation decreased the maximal number of binding sites (B(max)) from 7. 53 +/- 1.06 pmol/mg protein to 4.63 +/- 0.53 pmol/mg protein, in the absence and presence of 100 microM zinc, respectively, while the dissociation constant (K(d)) remained unchanged. Analysis of the GABA concentration-effect curve at the embryonic stage revealed that the addition of 100 microM zinc decreased E(max) values for GABA stimulation of chloride uptake from 26.46 +/- 2.64% to 16.40 +/- 1. 96%, while EC(50) values were unaffected. In conclusion, our results suggest that zinc acts as a non-competitive inhibitor of both GABA binding and GABA responses during avian CNS development, with its effect inversely related to age.

Hospital-acquired pneumonia: methicillin resistance and intensive care unit admission.

Although epidemiologic investigations of hospital-acquired pneumonia have certain intrinsic limitations because of the heterogeneity of the study populations, the difficulties in making a clinical diagnosis of nosocomial pneumonia, and the need for better microbiologic assays, recent studies have provided new and important data concerning the role of Staphylococcus aureus in this disease. This pathogen has now been identified as the most frequent cause of nosocomial pneumonia in hospitals in both Europe and the United States among patients in general hospital units as well as in the intensive care unit (ICU). Patients who have been treated with mechanical ventilation are at especially high risk for S. aureus pneumonia. The incidence of nosocomial pneumonia related to methicillin-resistant S. aureus (MRSA) has increased in recent years in many countries, especially among patients in the ICU. Because hospitalized patients with suspected nosocomial pneumonia often have many risk factors for MRSA infection, it seems advisable to include coverage of MRSA in the initial therapeutic regimen for these patients until MRSA infection is excluded.

Risk factors and outcome of nosocomial infections: results of a matched case-control study of ICU patients.

Intensive-care-unit (ICU) patients are at risk for both acquiring nosocomial infection and dying, and require a high level of therapy whether infection occurs or not. The objective of the present study was to precisely define the interrelationships between underlying disease, severity of illness, therapeutic activity, and nosocomial infections in ICU patients, and their respective influences on these patients' outcome. In a 10-bed medical ICU, we conducted a case-control study with matching for initial severity of illness, with daily monitoring of severity of illness and therapeutic activity scores, and with analysis of the contribution of nosocomial infections to patients' outcomes. Forty-one cases of patients who developed nosocomial infections during a 1-yr period were paired with 41 controls without nosocomial infection according to three criteria: age (+/- 5 yr), Acute Physiology and Chronic Health Evaluation II (APACHE II) score (+/- 5 points), and duration of exposure to risk. Successful matching was achieved for 118 of 123 (96%) variables. Neurologic failure on the third day after ICU admission was the sole independent risk factor for nosocomial infection (adjusted odds ratio [OR]: 1.34; 95% confidence interval [CI]: 1.09 to 1.64; p = 0.007). Unlike control patients, case patients showed no clinical improvement and required a high level of therapeutic activity between ICU admission and the day of infection. Mortality attributable to nosocomial infection was 44%. Excess length of stay and duration of antibiotic treatment attributable to nosocomial infection were 14 d and 10 d, respectively. Attributable therapeutic activity as measured with the Therapeutic Intervention Scoring System (TISS) and Omega score was 368 and 233 points, respectively. Such consequences were observed in patients who developed multiple infections. These findings suggest that a persistent high level of therapeutic activity and persistent impaired consciousness are risk factors for nosocomial infections in ICU patients. These infections are responsible for excess mortality, prolongation of stay, and excess therapeutic activity resulting in important cost overruns for health-care systems.

Neurosteroid modulation of GABA binding sites in developing avian central nervous system.

Our aim was to examine the effect of the potent neurosteroid 3 alpha-hydroxy-5 alpha-pregnan-20-one (3 alpha, 5 alpha-P) on [3H]-GABA binding to its receptor sites in the chick optic lobe. Binding was performed on synaptic membranes isolated at different stages of development and two different membrane preparation procedures were applied to expose high and low affinity GABA binding sites. The addition of 3 alpha, 5 alpha-P was shown to increase [3H]-GABA binding in an age- and concentration-dependent manner. Maximal stimulation for low affinity GABA binding sites was observed at hatching (130% enhancement), in fresh-washed as well as in frozen membranes. Saturation analysis performed on both membrane types disclosed that 3 alpha, 5 alpha-P increases the affinity of low affinity GABA binding sites without altering their maximal binding capacity. On the other hand, the augmenting effect at high affinity sites, displayed only in frozen membranes, was roughly 50% for all developmental stages. However, their saturation binding parameters remained unaltered in the presence of the steroid, suggesting that stimulation of such sites seems due to interference exerted by the low affinity site population. Findings indicate that 3 alpha, 5 alpha-P acts as an allosteric modulator only for low affinity GABA binding sites, displaying an age-dependent profile probably related to plastic events during visual pathway development.

Determination of total effective vascular compliance in patients with sepsis syndrome.

Changes in capacitance vessels have important consequences on cardiac filling pressure and fluid volume distribution in patients with sepsis syndrome. Vascular compliance may be evaluated from the slope of the relationship between changes in total blood volume (deltaTBV) and changes in central venous pressure (deltaCVP) during acute volume expansion (450 ml of gelatin fluid over 6 min), i.e., from the deltaTBV/deltaCVP ratio. The mean ratio (ml x mm Hg-1 x kg-1) was 2.03 +/- 0.21 in control subjects, 1.43 +/- 0.25 in mechanically ventilated patients without sepsis syndrome, and 0.94 +/- 0.24 in mechanically ventilated patients with sepsis syndrome (p < 0.0001 versus the other two groups). Based on echocardiographic determinations, cardiac performance was constantly found within the normal range (cardiac output ranged from 5.6 +/- 1.2 to 6.7 +/- 2.0 L/min in nonseptic patients from 6.8 +/- 1.9 to 7.8 +/- 2.2 in septic patients). Effective compliance of the total vascular bed is therefore reduced in patients with sepsis syndrome, independently of the hemodynamic modifications due to mechanical ventilation.

GABA-stimulated chloride uptake during avian CNS development: modulation by neurosteroids.

In the present report we studied the GABA-stimulated 36Cl- uptake during chick optic lobe development in order to establish the ontogenetic profile of the functional GABAA receptor complex. A concentration-dependent stimulation of 36Cl- influx by GABA was demonstrated, starting at developmental stages as early as 10 days of incubation. The maximal GABA-induced 36Cl- uptake changed significantly during ontogeny with highest values near hatching. However, GABA potency to stimulate ion influx remained unchanged. We also examined the effect of two neurosteroids, allopregnanolone and epipregnanolone, on GABA-stimulated 36Cl- influx at three developmental stages (embryonic day 14, post-hatching day 1 and adult stage). Both steroids enhanced ion uptake in a concentration-dependent manner, exerting greater stimulatory effects at early developmental stages. Allopregnanolone displayed EC50 values lower than epipregnanolone at all three time points and was also more potent at post-hatching stages. Analysis of the GABA concentration-effect curve disclosed that both steroid decreased EC50 values for GABA stimulation while Emax levels were unaffected. In conclusion, our results showed an early appearance of the GABA-associated chloride channel together with the ability of neurosteroids to modulate GABA-gating of such channel.

Improvement of internal jugular vein cannulation using an ultrasound-guided technique.

OBJECTIVE: To determine whether ultrasound guidance can help operators to improve the results of jugular vein access in the ICU. DESIGN: Prospective, randomized study. SETTING: General Intensive Care Unit of a University Hospital. PATIENTS: Seven-nine patients were assigned to internal jugular vein cannulation using anatomical landmarks alone (control group, n = 42) or with ultrasound guidance (ultrasound group, n = 37). INTERVENTION: All cannulations were performed by junior house staff under the direct supervision of a senior physician. In the ultrasound group, an ultrasonography (7.5 MHz) was used and the transducer was covered by a sterile sheath. The placement and direction of the cannulating needle were determined on the ultrasound image. MEASUREMENTS AND RESULTS: Internal jugular vein cannulation was successful in 37/37 (100%) patients in the ultrasound group and in 32/42 patients (76%) in the control group (p < 0.01). Average access time was longer in the control group (235 +/- 408 s vs 95 +/- 174 s, p = 0.06) and carotid artery puncture occurred in five patients in each group (p = 0.83). Jugular cannulation was successful at the first attempt in 26% in the control group and 43% in the ultrasound group (p = 0.11). Thirty-two patients (86%) in the ultrasound group and 23 patients (55%) in the control group (p < 0.05) were cannulated within 3 min. The cannula could therefore not be inserted within 3 min in 19 patients (45%) in the control group. Failure was explained by thrombosis (n = 1), small caliber of the internal jugular vein (< 5 mm, n = 3), abnormal vascular relations (n = 3). Among the ten primary failures of cannulation, an internal jugular vein catheter was able to be inserted in four cases by an experienced physician on the side initially selected and with ultrasound guidance in two cases. The catheter was inserted into the contralateral internal jugular vein under ultrasound guidance in the remaining four cases. CONCLUSION: Ultrasound guidance improved the success rate of jugular vein cannulation in ICU patients. Our results suggest that ultrasound guidance should be used when the internal jugular vein has not been successfully cannulated within 3 min by the external landmark-guided technique.

[Prevention of acquired pneumonia during artificial ventilation (excluding the use of anti-infectious agents)]. / Moyens de prévention des pneumopathies acquises lors de la ventilation artificielle (à l'exclusion de l'utilisation des anti-infectieux).

Nosocomial pneumonia remains a serious complication which occurs in patients who are artificially ventilated; as neither frequency nor important sequelae have altered recently inspite of the progress which has been achieved both with diagnosis and treatment. Preventative measures ought to be developed and realistically assessed before their introduction. Today it is indispensable to measure the impact of these measures, whether they have been previously or recently proposed by therapeutic trials. The current techniques proposed to prevent the appearance of nosocomial pneumonia are integrated in the usual conventional group of measures in the struggle against nosocomial infection which rests predominantly on standard approaches to hospital hygiene. These may be more specifically directed at good practical measures for the care of the ventilated patient. Regular toilet to the digestive and respiratory pathway, care of the ventilator material, absence of the changing of ventilation tubing during the stay. A certain number of measures are specifically suggested to prevent pneumonias: they have been imperfectly evaluated in clinical practice and remain controversial. Thus selective decontamination of the digestive system has not been dealt with her but also the sitting position, the utilisation of turning or oscillating beds, the continuous aspiration of oropharyngeal secretions or the use of Sucralfate as a means of prevention stress ulcers. Today, and until a complete evaluation of different techniques, the prevention of acquired pneumopathy during artificial ventilation rests above all on extremely simple measures; these cost little and are essentially meticulous care of the upper respiratory and digestive apparatus, to tracheal aspiration and physiotherapy which assure effective drainage and secretions, the use of the semi-sitting position, a well positioned gastric tube, in other words, basic care of the ventilated patient of a very good quality.

Diagnostic and therapeutic implications of transesophageal echocardiography in medical ICU patients with unexplained shock, hypoxemia, or suspected endocarditis.

OBJECTIVE: To evaluate the diagnostic and therapeutic implications of transesophageal echocardiography (TEE) in intensive care patients. DESIGN: Comparative study. SETTING: A 10-bed general intensive care unit. PATIENTS: Between 1 January 1992 and 31 May 1993, 61 patients prospectively identified with shock (n = 14), severe, unexplained hypoxemia (Partial pressure of oxygen in arterial blood/fractional inspired oxygen < 200) (n = 31), or suspected endocarditis (n = 16) underwent a TEE examination to supplement transthoracic echocardiography (TTE) examination. INTERVENTIONS: The results of each TEE examination were compared with the clinical findings and TTE data. TEE examinations were classified as follows: 0, TEE results were similar to TTE results; 00, TEE examination resulted in exclusion of suspected abnormalities; 1, TEE revealed a new but minor diagnosis compared to the TTE diagnosis; 2, TEE revealed a new major diagnosis not requiring a change of treatment; 3, TEE results revealed a new major diagnosis requiring an immediate change of treatment. RESULTS: Intraobserver reliability of the TEE classification was confirmed by a 100% concordance and interobserver reliability was evaluated as an 84% concordance. Results of the TEE classification were: class 0, n = 21 (34%); class 00, n = 13 (21%); class 1, n = 7 (12%); class 2, n = 8 (13%); class 3, n = 12 (20%). Therapeutic implications of TEE in class 3 patients were cardiac surgery in 5 patients (2 cases of acute mitral regurgitation, 2 valvular abscesses, and 1 hematoma compressing the left atrium), discontinuation of positive end-expiratory pressure in 1 ventilated patient with an atrial septal defect, weaning off mechanical ventilation in 1 patient with an atrial septal defect, prescription of antimicrobial therapy in 3 patients with endocarditis, and prescription of anticoagulant therapy in 2 patients with left atrial thrombus. No difficulty inserting the transducer was observed in any of the 61 patients studied. The only noteworthy complication was a case of spontaneously resolving atrial fibrillation. CONCLUSION: TEE is safe and well tolerated and is useful in the management of patients in the intensive care unit with shock, unexplained and severe hypoxemia, or suspected endocarditis when TTE is inconclusive.

Nosocomial pneumonia and mortality among patients in intensive care units.

OBJECTIVE: To evaluate the role that nosocomial pneumonia plays in the outcome of intensive care unit (ICU) patients. DESIGN: Cohort study. SETTING: Medical ICU, Hôpital Bichat, Paris, France, an academic tertiary care center. PATIENTS: A total of 1978 consecutive patients admitted to the ICU for at least 48 hours. MAIN OUTCOME MEASURES: Various parameters known to be strongly associated with death of ICU patients were recorded: age, location before admission to the ICU, diagnostic categories, Acute Physiology and Chronic Health Evaluation (APACHE) II score, Simplified Acute Physiologic Score, McCabe score, number and type of dysfunctional organs, and the development of nosocomial bacteremia and nosocomial urinary tract infection. These variables and the presence or absence of nosocomial pneumonia were compared between survivors and nonsurvivors and entered into a stepwise logistic regression model to evaluate their independent prognostic roles. RESULTS: Nosocomial pneumonia developed in 328 patients (16.6%) whose mortality was 52.4% compared with 22.4% for patients without ICU-acquired pneumonia (P < .001), APACHE II score (odds ratio [OR] = 1.08; 95% confidence interval [CI], 1.06 to 1.10; P < .001), number of dysfunctional organs (OR = 1.54; 95% CI, 1.36 to 1.74; P < .001), nosocomial pneumonia (OR = 2.08; 95% CI, 1.55 to 2.80; P < .001), nosocomial bacteremia (OR = 2.51; 95% CI, 1.78 to 3.55; P < .001), ultimately or rapidly fatal underlying disease (OR = 1.76; 95% CI, 1.38 to 2.25; P < .001), and admission from another ICU (OR = 1.30; 95% CI, 1.01 to 1.68; P =.04) were significantly associated with mortality. CONCLUSION: These data suggest that, in addition to the severity of underlying medical conditions and nosocomial bacteremia, nosocomial pneumonia independently contributes to ICU patient mortality.

Pentobarbital modulatory effect on GABA binding sites in developing chick optic lobe.

Barbiturates are allosteric modulators of the CNS GABAA receptor, increasing [3H]-GABA binding to its receptor sites. In the present work we have studied the modulatory effect of the barbiturate pentobarbital on low-affinity GABA binding sites during ontogenetic development of the chick optic lobe. Our results indicate that [3H]-GABA binding enhancement by pentobarbital shows a differential profile during development, following a two-component enhancement model at early stages of development and a single-component enhancement model in the adult stage. Kinetic analysis performed at different stages of development showed that barbiturate enhancement was invariably due to an increase in [3H]-GABA binding affinity, while maximal binding capacity remained unchanged. Using GABA antagonists, picrotoxinin and bicuculline, convulsant sensitivity of high-affinity barbiturate modulatory sites was found at early stages. These data suggest that barbiturate action displays receptor heterogeneity during development, with high- and low-affinity modulatory sites only at early stages, while the high-affinity sites disappear between hatching and adulthood. Kinetic data indicate that both barbiturate modulatory sites are coupled to the GABAA receptor at early stages. The presence of high-affinity modulatory sites at early stages and at hatching suggests a major role during visual pathway maturation.