Acute respiratory compromise describes a deterioration in respiratory function with a high likelihood of rapid progression to respiratory failure and death. Identifying patients at risk for respiratory compromise coupled with monitoring of patients who have developed respiratory compromise might allow earlier interventions to prevent or mitigate further decompensation. The National Association for the Medical Direction of Respiratory Care (NAMDRC) organized a workshop meeting with representation from many national societies to address the unmet needs of respiratory compromise from a clinical practice perspective. Respiratory compromise may arise de novo or may complicate preexisting lung disease. The group identified distinct subsets of respiratory compromise that present similar opportunities for early detection and useful intervention to prevent respiratory failure. The subtypes were characterized by the pathophysiological mechanisms they had in common: impaired control of breathing, impaired airway protection, parenchymal lung disease, increased airway resistance, hydrostatic pulmonary edema, and right-ventricular failure. Classification of acutely ill respiratory patients into one or more of these categories may help in selecting the screening and monitoring strategies that are most appropriate for the patient’s particular pathophysiology. Standardized screening and monitoring practices for patients with similar mechanisms of deterioration may enhance the ability to predict respiratory failure early and prevent its occurrence.
Extravascular lung water (EVLW) is a key variable in heart failure management and prognosis, but its objective assessment remains elusive. Lung imaging has been traditionally considered off-limits for ultrasound techniques due to the acoustic barrier of high-impedance air wall. In pulmonary congestion however, the presence of both air and water creates a peculiar echo fingerprint. Lung ultrasound shows B-lines, comet-like signals arising from a hyper-echoic pleural line with a to-and-fro movement synchronized with respiration. Increasing EVLW accumulation changes the normal, no-echo signal (black lung, no EVLW) into a black-and-white pattern (interstitial sub-pleural oedema with multiple B-lines) or a white lung pattern (alveolar pulmonary oedema) with coalescing B-lines. The number and spatial extent of B-lines on the antero-lateral chest allows a semi-quantitative estimation of EVLW (from absent, ≤5, to severe pulmonary oedema, >30 B-lines). Wet B-lines are made by water and decreased by diuretics, which cannot modify dry B-lines made by connective tissue. B-lines can be evaluated anywhere (including extreme environmental conditions with pocket size instruments to detect high-altitude pulmonary oedema), anytime (during dialysis to titrate intervention), by anyone (even a novice sonographer after 1 h training), and on anybody (since the chest acoustic window usually remains patent when echocardiography is not feasible). Cardiologists can achieve much diagnostic gain with little investment of technology, training, and time. B-lines represent ‘the shape of lung water’. They allow non-invasive detection, in real time, of even sub-clinical forms of pulmonary oedema with a low cost, radiation-free approach.
- Proceedings of the National Academy of Sciences of the United States of America
- Published over 1 year ago
The most common pediatric mitochondrial disease is Leigh syndrome, an episodic, subacute neurodegeneration that can lead to death within the first few years of life, for which there are no proven general therapies. Mice lacking the complex I subunit, Ndufs4, develop a fatal progressive encephalopathy resembling Leigh syndrome and die at ≈60 d of age. We previously reported that continuously breathing normobaric 11% O2 from an early age prevents neurological disease and dramatically improves survival in these mice. Here, we report three advances. First, we report updated survival curves and organ pathology in Ndufs4 KO mice exposed to hypoxia or hyperoxia. Whereas normoxia-treated KO mice die from neurodegeneration at about 60 d, hypoxia-treated mice eventually die at about 270 d, likely from cardiac disease, and hyperoxia-treated mice die within days from acute pulmonary edema. Second, we report that more conservative hypoxia regimens, such as continuous normobaric 17% O2 or intermittent hypoxia, are ineffective in preventing neuropathology. Finally, we show that breathing normobaric 11% O2 in mice with late-stage encephalopathy reverses their established neurological disease, evidenced by improved behavior, circulating disease biomarkers, and survival rates. Importantly, the pathognomonic MRI brain lesions and neurohistopathologic findings are reversed after 4 wk of hypoxia. Upon return to normoxia, Ndufs4 KO mice die within days. Future work is required to determine if hypoxia can be used to prevent and reverse neurodegeneration in other animal models, and to determine if it can be provided in a safe and practical manner to allow in-hospital human therapeutic trials.
Introduction: Paraphimosis is a urologic emergency. Many treatment options have been devised for managing this entity. The osmotic method is one of them. We used an osmotic diuretic, mannitol, for reducing paraphimosis. Mannitol is commonly used for conditions like head injury to decrease cerebral oedema, partial nephrectomy and hepatorenal syndrome; we attempted using this diuretic for reducing paraphimosis. This is a novel technique and an application of mannitol which has never been reported before. Methods: Starting in February 2011, we used mannitol 20% in patients presenting to urologic emergency with uncomplicated paraphimosis. Mannitol-soaked gauzes were wrapped around the oedematous prepuce, followed by minimal intermittent hand compression and frequent resoaking of the gauze with 20% mannitol. No needle punctures were made. The soaked gauze was removed and the paraphimosis was reduced easily. Results: A complete reduction of paraphimosis occurred after mannitol-soaked gauze had been placed over the oedematous prepuce for about 30-45 min in 6 of our patients. This is a novel agent used for this entity; it reduces paraphimosis in a minimal time with no pain, with the added advantage of the least risk of infection after the procedure as opposed to granulated sugar or 50% dextrose previously used as osmotic agents. Conclusions: Mannitol can be applied in clinical practice for reducing paraphimosis. It requires no anaesthesia and is associated with minimal/no patient discomfort unlike that seen with multiple needle punctures and the various other non-osmotic methods of reducing paraphimosis.
Introduction: Bradykinin-mediated angioedema is characterized by subcutaneous and/or submucosal edema formation without wheals and pruritus. It is linked to bradykinin-enhanced vascular permeability and, therefore, it does not respond to conventional measures, but requires specific therapy. Areas covered: This summary briefly reviews the different types of bradykinin-mediated angioedema and its remedies. Therapy focuses on relieving edema, as well as on decreasing its incidence and severity. The modes of the actions of attenuated androgens and antifibrinolytics are not precisely known - these agents have been introduced on an empirical basis. Contemporary treatments, by contrast, have been purposely developed to inhibit bradykinin. Most experience pertains to angioedema resulting from C1-inhibitor deficiency, and the controlled studies have focused on the hereditary form of this disease type (HAE). The pathomechanisms of HAE with normal C1-inhibitor activity, as well as of angiotensin-converting enzyme inhibitor-releated, and of non-histaminergic idiopathic sporadic angioedemas are largely unknown. Appropriate laboratory methods for the diagnosis, or specific interventions for the therapy of these conditions are not available or only available off-label. Expert opinion: In this case, diagnosis and management are challenging. The range of targeted therapeutic options has increased in recent years and includes measures to handle emergencies, prevent edematous episodes and manage additional types of bradykinin-mediated angioedema.
Blessed were the days when it all made sense and the apparent mechanism for edema formation in nephrotic syndrome was straightforward: the kidneys lost protein in the urine, which lowered the plasma oncotic pressure. Thus, fluid leaked into the interstitium, depleting the intravascular volume with subsequent activation of renin/aldosterone and consequent avid renal sodium retention. As simple as that! Unfortunately, a number of clinical and laboratory observations have raised serious concerns about the accuracy of this “underfill” hypothesis. Instead, an “overfill” hypothesis was generated. Under this assumption, the nephrotic syndrome not only leads to urinary protein wasting, but also to primary sodium retention with consequent intravascular overfilling, with the excess fluid spilling into the flood plains of the interstitium, leading to edema. Recently, an attractive mechanism was proposed to explain this primary sodium retention: proteinuria includes plasma proteinases, such as plasmin, which activate the epithelial sodium channel in the collecting duct, ENaC. In this edition, further evidence for this hypothesis is being presented by confirming increased plasmin content in the urine of children with nephrotic syndrome and demonstrating ENaC activation. If correct, this hypothesis would provide a simple treatment for the edema: pharmacological blockade of ENaC, for instance, with amiloride. Yet, how come clinicians have not empirically discovered the presumed power of ENaC blockers in nephrotic syndrome? And why is it that some patients clearly show evidence of intravascular underfilling? The controversy of over- versus underfilling demonstrates how much we still have to learn about the pathophysiology of nephrotic syndrome.
The anti-inflammatory activity of Canavalia seed lectins (Canavalia gladiata [CGL], Canavalia maritima [ConM] and Canavalia brasiliensis [ConBr]) was evaluated by intravenous administration in rats. In non-sensitized rats, cellular edema elicited by carrageenan was reduced (45-51 %) by ConM and (44-59 %) by CGL. Osmotic edema elicited by dextran was reduced by ConM and CGL in 27 % and 29 %. ConM and CGL reduced the edema elicited by L-arginine in 53 % and that of prostaglandin E(2) in 48 % and 36 %. Leukocyte migration elicited by carrageenan was reduced in 49 % by ConM and in 55 % by CGL (attenuated in 4× by glucose) and peritoneal TNF-α content in 82 %. In rats sensitized, ConM inhibited the paw edema and leukocyte migration elicited by ovalbumin in 34 % and 70 %. ConM and CGL are anti-inflammatory, mainly in cellular events mediated by prostaglandin E(2), nitric oxide and TNF-α in non-sensitized rats. However, only ConM is anti-inflammatory in sensitized rats. CGL effect involves the lectin domain.
Endotracheal intubation is frequently complicated by laryngeal edema, which may present as postextubation stridor or respiratory difficulty or both. Ultimately, postextubation laryngeal edema may result in respiratory failure with subsequent reintubation. Risk factors for postextubation laryngeal edema include female gender, large tube size, and prolonged intubation. Although patients at low risk for postextubation respiratory insufficiency due to laryngeal edema can be identified by the cuff leak test or laryngeal ultrasound, no reliable test for the identification of high-risk patients is currently available. If applied in a timely manner, intravenous or nebulized corticosteroids can prevent postextubation laryngeal edema; however, the inability to identify high-risk patients prevents the targeted pretreatment of these patients. Therefore, the decision to start corticosteroids should be made on an individual basis and on the basis of the outcome of the cuff leak test and additional risk factors. The preferential treatment of postextubation laryngeal edema consists of intravenous or nebulized corticosteroids combined with nebulized epinephrine, although no data on the optimal treatment algorithm are available. In the presence of respiratory failure, reintubation should be performed without delay. Application of noninvasive ventilation or inhalation of a helium/oxygen mixture is not indicated since it does not improve outcome and increases the delay to intubation.
BackgroundThe fatty acid amide palmitoylethanolamide (PEA) has been studied extensively for its anti-inflammatory and neuroprotective actions. The lipidic nature and large particle size of PEA in the native state may limit its solubility and bioavailability when given orally, however. Micronized formulations of a drug enhance its rate of dissolution and reduce variability of absorption when orally administered. The present study was thus designed to evaluate the oral anti-inflammatory efficacy of micronized/ultramicronized versus nonmicronized PEA formulations.MethodsMicronized/ultramicronized PEA was produced by the air-jet milling technique, and the various PEA preparations were subjected to physicochemical characterization to determine particle size distribution and purity. Each PEA formulation was then assessed for its anti-inflammatory effects when given orally in the carrageenan-induced rat paw model of inflammation, a well-established paradigm of edema formation and thermal hyperalgesia.ResultsIntraplantar injection of carrageenan into the right hind paw led to a marked accumulation of infiltrating inflammatory cells and increased myeloperoxidase activity. Both parameters were significantly decreased by orally given micronized PEA (PEA-m; 10 mg/kg) or ultramicronized PEA (PEA-um; (10 mg/kg), but not nonmicronized PeaPure (10 mg/kg). Further, carrageenan-induced paw edema and thermal hyperalgesia were markedly and significantly reduced by oral treatment with micronized PEA-m and ultramicronized PEA-um at each time point compared to nonmicronized PeaPure. However, when given by the intraperitoneal route, all PEA formulations proved effective.ConclusionsThese findings illustrate the superior anti-inflammatory action exerted by orally administered, micronized PEA-m and ultramicronized PEA-um, versus that of nonmicronized PeaPure, in the rat paw carrageenan model of inflammatory pain.
Angioedema is a rare but may be serious (laryngeal edema). This is a recurrent edema, subcutaneous and/or submucosal, whose cause is a hereditary or acquired deficiency in C1 inhibiteur (C1 inhibitor fraction of complement). We present the case of a 56 years old patient who showed recurrent episodes of swelling of the face and hands in association with chronic lymphocytic leukemia stage A. The exploration of the complement pathway has allowed retaining the diagnosis of acquired angioedema type I. The association of angioedema and lymphoproliferative syndrome is rare; we present this interesting case to discuss it from the literature data.