Social support during intensive care unit stay might improve mental impairment and consequently health-related quality of life in survivors of severe acute respiratory distress syndrome.

INTRODUCTION: We investigated health-related quality of life (HRQoL) and persistent symptoms of post-traumatic stress disorder (PTSD) in long-term survivors of acute respiratory distress syndrome (ARDS). We wished to evaluate the influence of PTSD on HRQoL and to investigate the influence of perceived social support during intensive care unit (ICU) treatment on both PTSD symptoms and HRQoL. METHODS: In ARDS patients we prospectively measured HRQoL (Medical Outcomes Study 36-Item Short Form; SF-36), symptoms of PTSD (Post-Traumatic Stress Syndrome 10-Questions Inventory; PTSS-10), perceived social support (Questionnaire for Social Support; F-Sozu) and symptoms of psychopathology (Symptom Checklist-90-R); and collected sociodemographic data including current employment status. Sixty-five (50.4%) out of 129 enrolled survivors responded, on average 57 +/- 32 months after discharge from ICU. Measuring symptoms of PTSD the PTSS-10 was used to divide the ARDS patients into two subgroups ('high-scoring patients', indicating patients with an increased risk for developing PTSD, and 'low-scoring patients'). RESULTS: HRQoL was significantly reduced in all dimensions in comparison with age- and gender-adjusted healthy controls. Eighteen patients (29%) were identified as being at increased risk for PTSD. PTSD risk was significantly linked with anxiety during their ICU stay. In this group of patients there was a trend towards permanent or temporary disability, independent of the period between discharge from ICU and study entry. Perceived social support was associated with a reduction in PTSD symptoms (Pearson correlation; p < 0.05). Post-hoc test revealed a significant difference between 'high-scoring patients' and 'low-scoring patients' with respect to mental health, although they did not differ in physical dimensions. CONCLUSION: HRQoL was reduced in long-term survivors, and was linked with an increased risk of chronic PTSD with ensuing psychological morbidity. This was independent of physical condition and was associated with traumatic memories of anxiety during their ICU stay. Social support might improve mental health and consequently long-term outcome including employment status.

Critical illness polyneuropathy and myopathy in patients with acute respiratory distress syndrome.

OBJECTIVE: Critical illness polyneuropathy/myopathy (CIP/CIM) is frequently described in critically ill patients who survive severe sepsis. Clinically relevant paresis is major symptom of CIP/CIM. We aimed at determining risk factors and diagnostic value of electrophysiologic testing for CIP/CIM in patients with acute respiratory distress syndrome (ARDS). DESIGN: Single-center, retrospective analysis, using charts. SETTING: University medical center. PATIENTS: Fifty consecutive ARDS patients in our intensive care unit. INTERVENTIONS: Patient characteristics and clinical course were analyzed. All patients received early electrophysiologic testing. CIP/CIM was diagnosed by the presence of clinical relevant paresis. MEASUREMENTS AND MAIN RESULTS: Clinically relevant paresis was confirmed in 27 ARDS patients (60%), whereas in 18 patients no paresis was determined (controls); five patients died before clinical assessment of paresis was feasible. Patients with paresis were older, had more days on mechanical ventilation, and had increased intensive care unit length of stay compared with controls. Patients who developed paresis had elevated daily peak blood glucose levels during 28 days of intensive care unit treatment: 166 (134, 200) mg/dL in CIP/CIM patients vs. 144 (132, 161) mg/dL in controls (median, quartiles). Twenty-five of 27 patients with paresis revealed reduced motor unit potentials, fibrillation potentials, or positive sharp waves on early electrophysiologic testing indicating CIP/CIM, whereas 16 of 18 control patients did not. CONCLUSIONS: In ARDS patients, paresis is a frequent complication causing prolonged mechanical ventilation and intensive care unit length of stay. An association between hyperglycemia and CIP/CIM has been found. However, since this is a retrospective survey, a causal relation is not clearly supported. In this study, the use of early electrophysiologic testing in ARDS patients was a valuable diagnostic tool for detecting CIP/CIM.

Inactivation of platelet glycoprotein IIb/IIIa receptor by nitric oxide donor 3-morpholino-sydnonimine.

Nitric oxide (NO) is known to modulate platelet adhesion and aggregation, which are both mediated by fibrinogen receptor glycoprotein (GP)IIb/IIIa. To investigate effects of NO on GPIIb/IIIa activation and inactivation, platelets were exposed to NO donor 3-morpholino-sydnonimine (SIN-1) before and after stimulation with different agonists: thromboxane analog U-46619, epinephrine, adenosine diphosphate, human a-thrombin, and phorbol-12-myristate-13-acetate (0.02 micromol/l). (1) Flow cytometry analysis of SIN-1-pre-incubated samples using PAC-1 monoclonal antibody revealed an inhibition of receptor activation by 80.9 +/- 1.2, 71.3 +/- 1.8, 56 +/- 4.9, 87 +/- 3.4, and 56 +/- 5% (mean +/- SEM, relative to baseline). (2) Administration of SIN-1 after stimulation reversed receptor activation by 55 +/- 5.2, 56 +/- 2.0, 53 +/- 5.4, 42 +/- 4.3, and 44 +/- 5%, respectively. With 0.1 micromol/l phorbol-12-myristate-13-acetate, GPIIb/IIIa activation was irreversible. (3) SIN-1 effects could completely be blocked by equimolar addition of guanylyl cyclase inhibitor 1H(1,2,4)oxadiazolo(4,3-alpha)quinoxalin-1-on. (4) Spontaneous receptor closure after activation with human alpha-thrombin and adenosine diphosphate was not due to platelet-derived NO; SIN-1, however accelerated spontaneous receptor inactivation. (5) SIN-1-inactivated receptors still responded to stimulation. In conclusion, SIN-1 or NO modulates GPIIb/IIIa conformational change in vitro via guanosine 3',5'-monophosphate-dependent pathways. Whereas spontaneous receptor inactivation may be enhanced by exogenous NO, platelet-derived NO is not involved in receptor inactivation.

Selective pulmonary vasodilation in acute respiratory distress syndrome.

Acute respiratory distress syndrome (ARDS) is characterized by a marked maldistribution of pulmonary perfusion in favor of nonventilated, atelectatic areas of the lungs, and it is the main cause of pulmonary right-to-left shunting and hypoxemia. Therapeutic interventions to selectively influence pulmonary perfusion in ARDS became feasible with the introduction of inhaled nitric oxide, which provided a means not only to reduce pulmonary hypertension, but also to improve matching of ventilation to perfusion and, thus, hypoxemia. Clinical studies in ARDS subsequently demonstrated that the combination of inhaled nitric oxide with other interventions, such as positive end-expiratory pressure and prone positioning, yielded beneficial and additive effects on arterial oxygenation. Although the available randomized, controlled trials of this novel concept have so far failed to show an improved outcome in ARDS, inhaled nitric oxide is a clinically valuable option for the treatment of severe refractory hypoxemia in ARDS, and largely promoted the concept of selective pulmonary vasodilation in intensive care practice. Currently, aerosolization of various vasodilators, in particular prostaglandins, is under evaluation in models of acute lung injury and human ARDS. Ongoing research aims to augment the effectiveness of vasodilators with specific inhibitors of phosphodiesterases or by combination with intravenous vasoconstrictors. Consequently, several alternative ways to selectively modulate pulmonary vascular tone in patients with ARDS may be available in the near future. Cost-benefit analysis of these therapeutic options will largely determine their future perspective.

Reduced nitric oxide in sinus epithelium of patients with radiologic maxillary sinusitis and sepsis.

Radiologic maxillary sinusitis is an important risk factor for development of bronchopneumonia in mechanically ventilated patients. Nitric oxide produced within the paranasal sinuses is considered to provide an antibacterial environment and to modulate mucociliary clearance function. We hypothesized that a reduced formation of nitric oxide might contribute to the compromised local host defense in radiologic maxillary sinusitis and measured nitric oxide levels directly within maxillary sinuses of septic patients with radiologic maxillary sinusitis (n = 11), whose sinuses were fenestrated to eliminate a possible septic focus. Data were compared with those of patients without airway inflammation (n = 11, control subjects). Despite local inflammation and infection, we found considerably lower maxillary nitric oxide levels than in control subjects (31 +/- 10 versus 2554 +/- 385 parts per billion, mean +/- standard error of the mean, p < 0.001). Consistently, immunohistochemical and in situ hybridization investigations revealed strongly reduced expression of inducible nitric oxide synthase. By applying ultrastructural immunolocalization, we identified cilia and microvilli of the maxillary sinus epithelium as the major nitric oxide production site in control subjects. Our findings provide evidence of markedly reduced nitric oxide production in maxillary sinuses of patients with radiologic maxillary sinusitis and sepsis, implicating impaired local host defense and an increased risk for secondary infections.

Dose-response characteristics during long-term inhalation of nitric oxide in patients with severe acute respiratory distress syndrome: a prospective, randomized, controlled study.

Inhaled nitric oxide (NO) improves systemic oxygenation (PaO2/FIO2) in adult patients with acute respiratory distress syndrome (ARDS). However, individual response varies, and previous trials demonstrated no outcome benefit. This prospective, randomized study in 40 ARDS patients analyzed dose-response (DR) characteristics during long-term inhaled NO. Patients were randomized for conventional therapy (control) or continuous treatment with 10 parts per million (ppm) inhaled NO until weaning was initiated. We measured DR curves of PaO2/FIO2 versus the inhaled NO dose at regular intervals. Before treatment (Day 0), peak improvement in PaO2/FIO2 was achieved at 10 ppm for both control and NO-treated patients. After 4 days, the DR curve of the NO-treated patients was left shifted with a peak response at 1 ppm. At higher doses (10 and 100 ppm), oxygenation deteriorated, and the response to inhaled NO disappeared in several patients. This effect was not observed in the control group. There was no effect of inhaled NO on duration of mechanical ventilation or stay at the intensive care unit. In conclusion, long-term inhaled NO with constant doses of 10 ppm leads to enhanced sensitivity after several days and does do not allow reduction of ventilation parameters. Hence, previous trials on therapy with inhaled NO in ARDS should be carefully interpreted, as they used constant NO concentrations, which may have become overdoses leading to deterioration of oxygenation after several days.

Immunologic and hemodynamic effects of "low-dose" hydrocortisone in septic shock: a double-blind, randomized, placebo-controlled, crossover study.

Within the last few years, increasing evidence of relative adrenal insufficiency in septic shock evoked a reassessment of hydrocortisone therapy. To evaluate the effects of hydrocortisone on the balance between proinflammatory and antiinflammation, 40 patients with septic shock were randomized in a double-blind crossover study to receive either the first 100 mg of hydrocortisone as a loading dose and 10 mg per hour until Day 3 (n = 20) or placebo (n = 20), followed by the opposite medication until Day 6. Hydrocortisone infusion induced an increase of mean arterial pressure, systemic vascular resistance, and a decline of heart rate, cardiac index, and norepinephrine requirement. A reduction of plasma nitrite/nitrate indicated inhibition of nitric oxide formation and correlated with a reduction of vasopressor support. The inflammatory response (interleukin-6 and interleukin-8), endothelial (soluble E-selectin) and neutrophil activation (expression of CD11b, CD64), and antiinflammatory response (soluble tumor necrosis factor receptors I and II and interleukin-10) were attenuated. In peripheral blood monocytes, human leukocyte antigen-DR expression was only slightly depressed, whereas in vitro phagocytosis and the monocyte-activating cytokine interleukin-12 increased. Hydrocortisone withdrawal induced hemodynamic and immunologic rebound effects. In conclusion, hydrocortisone therapy restored hemodynamic stability and differentially modulated the immunologic response to stress in a way of antiinflammation rather than immunosuppression.

Pulmonary air embolism in severe head injury.

Entry of air into the venous system leading to intracardiac air and pulmonary air embolism (PAE) has been reported in various clinical settings such as neurosurgical interventions in the sitting position and in autopsies on patients with head and neck injuries. We report the case of a 29-year-old male who developed severe pulmonary dysfunction after severe head injury in a high-velocity car accident. Chest X-ray showed bilateral diffuse patchy infiltrates. Pneumothorax, haemothorax, pulmonary aspiration, various forms of pulmonary oedema and pulmonary contusion could be excluded. Furthermore, there was an open laceration of the frontal sinus and maxillo-facial fractures. The history of spontaneous respiration in sitting position at the scene, rapid improvement of pulmonary function within 30 h, small amounts of air in the brain parenchyma, and circulatory shock despite elevated central venous pressure in the initial phase led to the diagnosis of PAE as the primary cause of pulmonary dysfunction. The diagnostic approach and basic therapeutical principles in patients with PAE are described. In conclusion, the case presented emphasizes the importance of considering PAE as a possible cause of respiratory failure in patients with severe head injury.