Inhaled Nitroglycerin for Pulmonary Edema in Air Medical Services: A Retrospective Pilot Study.

OBJECTIVE: The use of traditional inhaled pulmonary vasodilators, such as nitric oxide, to treat symptomatic pulmonary edema is not practical in the air medical or prehospital environment because of difficulty with administration. A hospital-based critical care air medical transport service initiated a pilot study to investigate the use of inhaled nitroglycerin (iNTG) as an alternative pulmonary vasodilator. METHODS: For this pilot study, iNTG was administered using a jet nebulizer setup and concentrated nitroglycerin, both of which are widely available in acute care settings. In conjunction with medical oversight, transport personnel identified patients with respiratory distress secondary to pulmonary edema. Twenty-two months after initiating the protocol, a retrospective chart review was conducted. Data for patients receiving iNTG were retrospectively abstracted through a medical record search and manual chart review. RESULTS: Twelve patients received iNTG during the pilot study. Basic demographics, medical comorbidities, concurrent medications, laboratory values, and radiographic studies were collected for each patient. Basic statistics were performed to identify any potential trends. CONCLUSION: The administration of iNTG is feasible in an air medical transport setting and may provide a useful adjunct to treating patients with pulmonary edema and respiratory distress. Because iNTG delivery targets the pulmonary vasculature, this may be of particular benefit in patients with a poor hemodynamic profile. Larger randomized controlled or cohort studies are needed to specifically analyze and compare hemodynamics, diagnostics, and patient outcomes.

Effect of furosemide in the treatment of high-altitude pulmonary edema.

BACKGROUND: High-altitude pulmonary edema (HAPE) refers to the onset of breathlessness, cough, and fever at rest after arriving at high altitudes. It is a life-threatening illness caused by rapid ascent to high altitudes. Furosemide is controversial in HAPE treatment but is routinely used in China. Further research is needed to assess its efficacy and impact on HAPE management and prognosis. The aim of this study is to determine the effectiveness of furosemide for HAPE. METHODS: A retrospective was conducted to analysis of patients with HAPE admitted to the People's Hospital of Shigatse City from January 2018 to September 2023. Patients were divided into furosemide group and non-furosemide group for further analysis. Clinical variables including demographic information, comorbidities, vital signs, inflammatory markers, biochemical analysis, CT severity score and prognostic indicators were collected. RESULTS: A total of 273 patients were enrolled, with 209 patients in the furosemide group and 64 patients in the non-furosemide group. The furosemide group showed a significantly decrease in CT severity scores compared to the non-furosemide group. Subgroup analysis showed that the longer the duration of furosemide use, the more pronounced the improvement in lung CT severity scores. But there were no significant differences in length of hospital stay and in-hospital mortality between the two groups. CONCLUSION: Furosemide helps alleviate pulmonary edema in HAPE patients, but further research is needed to clarify its impact on prognosis.

High-dose versus low-dose intravenous nitroglycerine for sympathetic crashing acute pulmonary edema: a randomised controlled trial.

OBJECTIVES: Sympathetic crashing acute pulmonary edema (SCAPE) is a subset of heart failure with a dramatic presentation. The unique physiology of this condition requires a different management strategy from the conventional practice. The trial objective was to compare the efficacy of high-dose and low-dose GTN in patients with SCAPE. METHODS: This was an open-label randomised control trial conducted in a tertiary care teaching hospital in India from 11 November 2021 to 30 November 2022. Consenting participants were randomised to high-dose GTN or conventional low-dose GTN. The primary outcome was symptom resolution at 6 hours and 12 hours. Secondary outcomes included intubation rates, admission rates, length of hospital stay, and any short-term adverse effects of GTN and major adverse cardiac events (MACE) at 30 days. RESULTS: Fifty-four participants were included (26 high-dose GTN, 26 low-dose GTN). At 6 hours, symptom resolution was seen in 17 patients (65.4%) in the 'high-dose' group, compared with 3 (11.5%) in the 'low-dose' group (p<0.001). At 12 hours, 88.5% of patients had a clinical resolution in the 'high-dose' arm versus 19.5% in 'low-dose' arm . The low-dose group had longer median hospital stay (12 hours vs 72 hours), more frequent MACE (3.8% vs 26.9%, p=0.02) and a higher intubation rate (3.8% vs 19.2%, p=0.08). The only short-term adverse effect seen was a headache in both the groups. CONCLUSION: In SCAPE, patients receiving high-dose GTN (>100 mcg/min) had earlier symptom resolution compared with the conventional 'low dose' GTN without any significant adverse effects. TRIAL REGISTRATION: Clinical trial registry of India (CTRI/2021/11/037902).

Pressure-sensitive multivesicular liposomes as a smart drug-delivery system for high-altitude pulmonary edema.

Changes in bodily fluid pressures, such as pulmonary artery pressure, play key roles in high-altitude pulmonary edema (HAPE) and other disorders. Smart delivery systems releasing a drug in response to these pressures might facilitate early medical interventions. However, pressure-responsive delivery systems are unavailable. We here constructed hydrostatic pressure-sensitive multivesicular liposomes (PSMVLs) based on the incomplete filling of the internal vesicle space with neutral lipids. These liposomes were loaded with amlodipine besylate (AB), a next-generation calcium channel inhibitor, to treat HAPE on time. AB-loaded PSMVLs (AB-PSMVLs) were destroyed, and AB was released through treatment under hydrostatic pressure of at least 25 mmHg. At 25 mmHg, which is the minimum pulmonary artery pressure value in HAPE, 38.8% of AB was released within 1 h. In a mouse HAPE model, AB-PSMVLs concentrated in the lung and released AB to diffuse into the vascular wall. Intravenously injected AB-PSMVLs before HAPE modeling resulted in a stronger protection of lung tissues and respiratory function and lower occurrence of pulmonary edema than treatment with free drug or non-pressure-sensitive AB-loaded liposomes. This study offers a new strategy for developing smart drug delivery systems that respond to changes in bodily fluid pressures.

Lung ultrasound and diuretic therapy in chronic heart failure: a randomised trial.

BACKGROUND: Lung congestion is frequent in heart failure (HF) and is associated with symptoms and poor prognosis. Lung ultrasound (LUS) identification of B-lines may help refining congestion assessment on top of usual care. Three small trials comparing LUS-guided therapy to usual care in HF suggested that LUS-guided therapy could reduce urgent HF visits. However, to our knowledge, the usefulness of LUS in influencing loop diuretic dose adjustment in ambulatory chronic HF has not been studied. AIMS: To study whether to show or not LUS results to the HF assistant physician would change loop diuretic adjustments in "stable" chronic ambulatory HF patients. METHODS: Prospective randomised single-blinded trial comparing two strategies: (1) open 8-zone LUS with B-line results available to clinicians, or (2) blind LUS. The primary outcome was change in loop diuretic dose (up- or down-titration). RESULTS: A total of 139 patients entered the trial, 70 were randomised to blind LUS and 69 to open LUS. The median (percentile25-75) age was 72 (63-82) years, 82 (62%) were men, and the median LVEF was 39 (31-51) %. Randomisation groups were well balanced. Furosemide dose changes (up- and down-titration) were more frequent among patients in whom LUS results were open to the assistant physician: 13 (18.6%) in blind LUS vs. 22 (31.9%) in open LUS, OR 2.55, 95%CI 1.07-6.06. Furosemide dose changes (up- and down-titration) were more frequent and correlated significantly with the number of B-lines when LUS results were open (Rho = 0.30, P = 0.014), but not when LUS results were blinded (Rho = 0.19, P = 0.13). Compared to blind LUS, when LUS results were open, clinicians were more likely to up-titrate furosemide dose if the result "presence of pulmonary congestion" was identified and more likely to decrease furosemide dose in the case of an "absence of pulmonary congestion" result. The risk of HF events or cardiovascular death did not differ by randomisation group: 8 (11.4%) in blind LUS vs. 8 (11.6%) in open LUS. CONCLUSIONS: Showing the results of LUS B-lines to assistant physicians allowed more frequent loop diuretic changes (both up- and down-titration), which suggests that LUS may be used to tailor diuretic therapy to each patient congestion status.

Suspected stonefish envenomation in Queensland over eight years: a retrospective series.

INTRODUCTION: Stonefish envenomation results in localized severe pain and swelling and systemic features, including vomiting, arrhythmia, pulmonary oedema, and possibly death. There are limited data regarding the effectiveness of the available antivenom. The aim of this series is to characterize presentations of patients with suspected stonefish envenomation and investigate treatment, including antivenom. METHODS: This is a retrospective observational series of suspected stonefish envenomation as reported to the Queensland Poisons Information Centre or Princess Alexandra Hospital Clinical Toxicology Unit from July 2015 to January 2023. Patients were identified through the databases held by both the Centre and Unit, and data on clinical features and investigations were collected from the patient's electronic medical record. RESULTS: There were 87 suspected stonefish envenomations from July 2015 to January 2023. The median age was 26 (range: 5-69) years, and 69 (79 per cent) patients were male. Pain was reported in 85 (98 per cent) with a median peak pain score of 10 (range 4-12; three rated their pain greater than 10/10). A clear wound was documented in 64 (74 per cent), with local swelling in 63 (72 per cent). A foreign body was retained in eight (9 per cent) presentations. Systemic symptoms were rare, with vomiting in four (5 per cent) and dizziness in two (2 per cent) presentations. There were no instances of hypotension, arrhythmia, or pulmonary oedema. Hot water was administered in 72 (83 per cent) presentations. Oral analgesia was given in 55 (63 per cent). Parenteral analgesia was given in 53 (61 per cent), most commonly opioids. Local anaesthetic block was performed in 19 presentations (22 per cent), with effectiveness documented in 16/19 (84 per cent). Five patients received antivenom for intractable pain, and all received subsequent parenteral analgesia or local anaesthetic block. CONCLUSIONS: Stonefish envenomation is characterized by severe pain. Systemic symptoms were rare and not severe in this series. Local anaesthetic block appeared to be the most effective intervention for severe pain when performed. Antivenom appeared to be ineffective in managing pain.

[Mechanism of dexamethasone combined with glutamine in reducing lung inflammation and pulmonary edema in rats with acute lung injury].

Objective To investigate the effect of dexamethasone (DEX) combined with glutamine (Gln) on lung inflammation and pulmonary edema in rats with acute lung injury induced by lipopolysaccharide (LPS) and its related mechanisms. Methods Fifty Wistar rats were randomly divided into control group, model group, dexamethasone group (DEX) and DEX combined with Gln group. Except for the control group, rats in other groups were injected with 6 mg/kg LPS intraperitoneally to induce an acute lung injury. The mRNA expression of p38 MAPK, NLRP3, and NF-κB in lung tissue were detected by real-time quantitative PCR. The protein expressions of p-p38 MAPK, NLRP3, phosphorylated inhibitor of nuclear factor κB (p-IκB), NF-κB p65, aquaporin 1 (AQP1) and AQP5 in lung tissue were detected by Western blot analysis. ELISA was used to detect the content of serum tumor necrosis factor-α (TNF-α), interleukin 6 (IL-6), interleukin 1ß (IL-1ß). Spectrophotometer was employed to detect the content of superoxide dismutase (SOD), malondialdehyde (MDA) and glutathione peroxidase (GSH-Px) in lung tissue. Results Compared with the control group, the lung index of the model group decreased, the content of the serum inflammatory factors TNF-α, IL-6 and IL-1ß significantly increased, and the protein expression of p38 MAPK, NLRP3, NF-κB mRNA, p-p38 MAPK, NLRP3, p-IκB and NF-κB p65 in the lung tissue significantly increased, while that of AQP1, AQP5 decreased, and the content of SOD and GSH-Px in lung tissue decreased, while that of MDA increased; Compared with the model group, the above mentioned symptoms and indicators in each treatment group were significantly improved, among which the DEX combined with Gln group was the most significant. Conclusion DEX combined with Gln can inhibit inflammation, resist oxidative damage, relieve pulmonary edema, and prevent acute lung injury. Its mechanism is related to inhibiting the activation of p38 MAPK, NLRP3, and NF-κB signaling pathways, promoting the expression of AQP1 and AQP5, and promoting the activity of antioxidant products.

Inhibition of S100A9 alleviates neurogenic pulmonary edema after subarachnoid hemorrhage.

BACKGROUND AND PURPOSE: Neurogenic pulmonary edema (NPE) frequently arises as a complication subsequent to subarachnoid hemorrhage (SAH). Heterodimers of S100A8 and S100A9 are commonly formed, thereby initiating an inflammatory reaction through receptor binding on the cell surface. Paquinimod serves as a specific inhibitor of S100A9. The objective of this investigation is to assess the impact of Paquinimod administration and S100A9 knockout on NPE following SAH. METHODS: In this study, SAH models of C57BL/6J wild-type (WT) and S100A9 knockout mice were established through intravascular perforation. These models were then divided into several groups, including the WT-sham group, S100A9-KO-sham group, WT-SAH group, WT-SAH + Paquinimod group, and S100A9-KO-SAH group. After 24 h of SAH induction, pulmonary edema was assessed using the lung wet-dry weight method and Hematoxylin and eosin (HE) staining. Additionally, the expression levels of various proteins, such as interleukin-1ß (IL-1ß), tumor necrosis factor α (TNF-α), occludin, claudin-3, Bax, Bcl-2, TLR4, MYD88, and pNF-κB, in lung tissue were analyzed using western blot and immunofluorescence staining. Lung tissue apoptosis was detected by TUNEL staining. RESULTS: Firstly, our findings indicate that the knockout of S100A9 has a protective effect on early brain injury following subarachnoid hemorrhage (SAH). Additionally, the reduction of brain injury after SAH can also alleviate neurogenic pulmonary edema (NPE). Immunofluorescence staining and western blot analysis revealed that compared to SAH mice with wild-type S100A9 expression (WT-SAH), the lungs of S100A9 knockout SAH mice (S100A9-KO-SAH) and mice treated with Paquinimod exhibited decreased levels of inflammatory molecules (IL-1ß and TNF-α) and increased levels of tight junction proteins. Furthermore, the knockout of S100A9 resulted in upregulated expression of the apoptotic-associated protein Bax and down-regulated expression of Bcl-2. Furthermore, a decrease in TLR4, MYD88, and phosphorylated pNF-κB was noted in S100A9-KO-SAH and Paquinimod treated mice, indicating the potential involvement of the TLR4/MYD88/NF-κB signaling pathway in the inhibition of the protective effect of S100A9 on NPE following SAH. CONCLUSION: The knockout of S100A9 not only ameliorated initial cerebral injury following subarachnoid hemorrhage (SAH), but also mitigated SAH-associated neurogenic pulmonary edema (NPE). Additionally, Paquinimod was found to diminish NPE. These findings imply a correlation between the central nervous system and peripheral organs, highlighting the potential of safeguarding the brain to mitigate harm to peripheral organs.

Kaempferol and ginsenoside Rg1 ameliorate acute hypobaric hypoxia induced lung injury based on network pharmacology analysis.

Acute hypobaric hypoxia at high altitude can cause fatal non-cardiogenic high altitude pulmonary edema. Anti-inflammatory and anti-oxidant treatments appear to be a prospective way to alleviate acute hypoxia lung injury. Kaempferol (KA) and ginsenoside Rg1 (GRg1) can be isolated and purified from ginseng with anti-inflammatory, antioxidant, anti-carcinogenic, neuroprotective, and antiaging effects. However, their effects and pharmacological mechanisms on lung injury remains unclear. Network pharmacology analyses were used to explore potential targets of KA and GRg1 against acute hypobaric hypoxia induced lung injury. Rat lung tissues were further used for animal experiment verification. Among the putative targets of KA and GRg1 for inhibition of acute hypobaric hypoxia induced lung injury, AKT1, PIK3R1, PTK2, STAT3, HSP90AA1 and AKT2 were recognized as higher interrelated targets. And PI3K-AKT signaling pathway is considered to be the most important and relevant pathway. The rat experimental results showed that KA and GRg1 significantly improved histopathological changes and decreased pulmonary edema in rats with lung injury caused by acute hypobaric hypoxia. The concentrations of IL-6, TNF-α, MDA, SOD and CAT in rats treated with KA and GRg1 were significantly ameliorated. Protein and mRNA levels of PI3K and AKTI were significantly inhibited after KA administration. KA and GRg1 can lower lung water content, improve lung tissue damage, reduce the production of pro-inflammatory cytokines and the oxidative stress level.

Signal of harm in morphine use in adults with acute pulmonary oedema: A rapid systematic review.

BACKGROUND: Heart failure affects nearly 65 million people globally, resulting in recurrent hospital admissions and substantial healthcare expenditure. The use of morphine in the management of acute pulmonary oedema remains controversial, with conflicting guidance and significant variation in practice. Synthesised evidence is needed to inform standard treatment guidelines and clinical practice. OBJECTIVE: To determine whether morphine should be used in the treatment of acute pulmonary oedema (APE) in adults. METHODS: A rapid review of systematic reviews of randomised controlled trials or observational studies, and then randomised controlled trials, was conducted searching three electronic databases (PubMed, Embase, Cochrane Library) and one clinical trial registry on 12 February 2022. We used a prespecified protocol following Cochrane rapid review methods and aligned to the National Standard Treatment Guidelines and Essential Medicines List methodology. We first considered relevant high-quality systematic reviews of randomised controlled trials or observational studies, then (if required) randomised controlled trials to inform time-sensitive or urgent evidence requests, clinical practice, policy, or standard treatment guidelines. RESULTS: We identified four systematic reviews of observational studies. The two most relevant, up-to-date, and highest-quality reviews were used to inform evidence for critical outcomes. Morphine may increase in-hospital mortality (odds ratio (OR) 1.78; 95% confidence interval (CI) 1.01 - 3.13; low certainty of evidence; six observational studies, n=151 735 participants), resulting in 15 more per 1 000 hospital deaths, ranging from 0 to 40 more hospital deaths. Morphine may result in a large increase in invasive mechanical ventilation (OR 2.72; 95% CI 1.09 - 6.80; low certainty of evidence; four observational studies, n=167 847 participants), resulting in 45 more per 1 000 ventilations, ranging from 2 more to 136 more. Adverse events and hospital length of stay were not measured across reviews or trials. CONCLUSION: Based on the most recent, relevant and best-available quality evidence, morphine use in adults with APE may increase in-hospital and all-cause mortality and may result in a large increase in the need for invasive mechanical ventilation compared to not using morphine. Recommending against the use of morphine in pulmonary oedema may improve patient outcomes. Disinvesting in morphine for this indication may result in cost savings, noting the possible accrued benefits of fewer patients requiring invasive ventilation and management of morphine-related side-effects.

Treatment of recurrent hunting-associated respiratory distress episodes in 2 dogs.

Noncardiogenic pulmonary edema (NCPE) in hunting dogs is an uncommon and poorly described condition for which no preventive treatment is available. Two dogs were presented for recurrent respiratory distress strictly associated with hunting activities. Diagnosis was based on bilateral, symmetrical, interstitial-to-alveolar pattern in the caudodorsal lung fields on thoracic radiographs, exclusion of other causes, and spontaneous clinical and radiographic improvement. Considering that the pathogenesis of exercise-induced NCPE likely involves α- and ß-adrenergic overstimulation, treatment with sympathetic blockers was used in both dogs. The first dog no longer showed respiratory signs during hunting activities. However, treatment failed to prevent respiratory distress in the other dog. Based on the large number of red blood cells in the bronchoalveolar lavage fluid of the second dog, exercise-induced pulmonary hemorrhage was suspected, as described in racing horses. The loop diuretic furosemide successfully prevented further hunting-associated respiratory distress episodes in this dog.

The effects of Crocus sativus extract on inhaled paraquat-induced lung inflammation, oxidative stress, pathological changes and tracheal responsiveness in rats.

Paraquat is a green liquid toxin that is used in agriculture and can induce multi-organ including lung injury. Various pharmacological effects of Crocus sativus (C. sativus) were indicated in previous studies. In this research, the effects of C. sativus extract and pioglitazone on inhaled paraquat-induced lung inflammation, oxidative stress, pathological changes, and tracheal responsiveness were studied in rats. Eight groups of rats (n = 7 in each) including control (Ctrl), untreated paraquat aerosol exposed group (54 mg/m3, 8 times in alternate days), paraquat treated groups with dexamethasone (0.03 mg/kg/day, Dexa) as positive control, two doses of C. sativus extract (20 and 80 mg/kg/day, CS-20 and CS-80), pioglitazone (5 and 10 mg/kg/day, Pio-5 and Pio-10), and the combination of CS-20 + Pio-5 were studied. Total and differential WBC, levels of oxidant and antioxidant biomarkers in the BALF, lung tissue cytokine levels, tracheal responsiveness (TR), and pathological changes were measured. The levels of IFN-γ, IL-10, SOD, CAT, thiol, and EC50 were reduced, but MDA level, total and differential WBC count in the BALF and lung pathological changes were increased in the paraquat group (all, p < 0.001). The levels of IFN-γ, IL-10, SOD, CAT, thiol and EC50 were increased but BALF MDA level, lung pathological changes, total and differential WBC counts were reduced in all treated groups. The effects of C. sativus high dose and combination groups on measured parameters were equal or even higher than dexamethasone (p < 0.05 to p < 0.001). The effects of the combination of CS-20 + Pio-5 on most variables were significantly higher than CS-20 and Pio-5 alone (p < 0.05 to p < 0.001). C. sativus treatment improved inhaled paraquat-induced lung injury similar to dexamethasone and showed a synergistic effect with pioglitazone, suggesting possible PPAR-γ receptor-mediated effects of the plant.

Demethyleneberberine alleviates Pseudomonas aeruginosa-induced acute pneumonia by inhibiting the AIM2 inflammasome and oxidative stress.

BACKGROUND: Acute pneumonia induced by Pseudomonas aeruginosa is characterized by massive infiltration of inflammatory cell and the production of reactive oxygen species (ROS), which lead to severe and transient pulmonary inflammation and acute lung injury. However, P.aeruginosa infection is resistant to multiple antibiotics and causes high mortality in clinic, the search for alternative prophylactic and therapeutic strategies is imperative. PURPOSE: This study was aimed to investigate the anti-inflammatory and antioxidant effects of DMB, a novel derivative of berberine, and explore the role of AIM2 inflammasome in P. aeruginosa-induced acute pneumonia. METHODS: Acute pneumonia mice were established by tracheal injection of P. aeruginosa suspension. Pathological changes of lung tissue were observed by its appearance and H&E staining. The lung coefficient ratio was measured to evaluate pulmonary edema. Inflammatory factors were detected by qRT-PCR, western blotting and immunohistochemistry. ROS and other indicators of oxidative damage were analyzed by flow cytometry and specific kit. Proteins related to AIM2 inflammasome were detected by western blotting. RESULTS: Compared with the P. aeruginosa-induced group, DMB ameliorated pulmonary edema, hyperemia, and pathological damage based on its appearance and H&E staining in DMB groups. First, DMB attenuated the inflammatory response induced by P.aeruginosa. Compared with the P. aeruginosa-induced group, the lung coefficient ratio was decreased by 31.5%, the MPO activity of lung tissue was decreased by 44.0%, the mRNA expression levels of TNF-α, IL-1ß and IL-6 were decreased by 64.8%, 51.2% and 64.0% respectively, and those protein expression levels were decreased by 40.1%, 42.8% and 47.8% respectively, and the number of white blood cells, neutrophils and monocytes were decreased by 53.5%, 29.4% and 13.7% in high dose (200 mg/kg) DMB group. Second, DMB alleviates oxidative stress in the lung tissue during P. aeruginosa-induced acute pneumonia. Compared with the P. aeruginosa-induced group, the level of GSH was increased by 42.5% and MDA was decreased by 49.5% in high dose DMB group. Moreover, the western blotting results showed that DMB markedly suppressed the expression of AIM2, ASC, Cleaved caspase1 and decreased the secretion of IL-1ß. Additionally, these results were also confirmed by in vitro experiments using MH-S and BEAS-2B cell lines. CONCLUSIONS: Taken together, these results indicated that DMB ameliorates P. aeruginosa-induced acute pneumonia through anti-inflammatory, antioxidant effects, and inhibition of AIM2 inflammasome activation.

Taming the Tiger: Ultra high dose nitroglycerin in managing sympathetic crashing acute pulmonary edema patient.

INTRODUCTION: Sympathetic Crashing Acute Pulmonary Edema (SCAPE) lies on the end of the acute heart failure syndrome spectrum with pulmonary edema in all lung zones. NTG at lower doses (10-20 µg/min) cause preload reduction, and at higher doses (> 100 µg/min) causes after-load reduction by arterial dilatation. The main aim is to decrease the afterload at the earliest to cut the vicious cycle caused by sudden sympathetic upsurge. To our knowledge, this is the highest nitroglycerin dose usage in the literature. CASE: A 60-year-old male with no known prior co-morbidities presented to our Emergency with complaints of acute onset severe shortness of breath, which was also associated with extreme diaphoresis, agitation, anxiety, and palpitations. On Examination, the patient was hypoxic and hypertensive with severe tachypnea and tachycardia. On Auscultation, diffuse bilateral crackles in all areas were heard. Point of care ultrasound showed bilateral B-profile in all lung zones, inferior vena cava was >50% collapsible. We managed the patient with non-invasive ventilation and ultrahigh dose nitroglycerin/ highest ever- 9 mg intravenous bolus with 76 mg infusion. The patient had improved within hours and did not require oxygen. The patient was discharged from the emergency after a few hours of observation. DISCUSSION: SCAPE occurs due to a vicious spiral involving increasing sympathetic outflow, excessive afterload, and worsening heart failure. The central, defining pathophysiological feature of SCAPE is pathologically elevated afterload due to systemic vasoconstriction and hypertension. SCAPE patients may be euvolemic, hypovolemic or hypervolemic. The problem is shift of fluid into the lungs rather than hypervolemia. The emphasis on treating pulmonary edema has shifted from diuretics to vasodilators, especially high-dose nitrates, combined with non-invasive positive pressure ventilation. CONCLUSION: This is the first report describing the safe and effective administration of ultra-high dose bolus/ highest dose ever and prolonged high-dose infusion for SCAPE, along with Non-invasive ventilation, which has prevented mechanical ventilation and mortality. High doses of intravenous NTG are extremely effective and safe for SCAPE patients.

Diuresis-matched versus standard hydration in patients undergoing percutaneous cardiovascular procedures: meta-analysis of randomized clinical trials.

INTRODUCTION AND OBJECTIVES: Contrast-associated acute kidney injury (CA-AKI) is a potential complication of procedures requiring administration of iodinated contrast medium. RenalGuard, which provides real-time matching of intravenous hydration with furosemide-induced diuresis, is an alternative to standard periprocedural hydration strategies. The evidence on RenalGuard in patients undergoing percutaneous cardiovascular procedures is sparse. We used a Bayesian framework to perform a meta-analysis of RenalGuard as a CA-AKI preventive strategy. METHODS: We searched Medline, Cochrane Library and Web of Science for randomized trials of RenalGuard vs standard periprocedural hydration strategies. The primary outcome was CA-AKI. Secondary outcomes were all-cause death, cardiogenic shock, acute pulmonary edema, and renal failure requiring renal replacement therapy. A Bayesian random-effect risk ratio (RR) with corresponding 95% credibility interval (95%CrI) was calculated for each outcome. PROSPERO database number CRD42022378489. RESULTS: Six studies were included. RenalGuard was associated with a significant relative reduction in CA-AKI (median RR, 0.54; 95%CrI, 0.31-0.86) and acute pulmonary edema (median RR, 0.35; 95%CrI, 0.12-0.87). No significant differences were observed for the other secondary endpoints [all-cause death (RR, 0.49; 95%CrI, 0.13-1.08), cardiogenic shock (RR, 0.06; 95%CrI, 0.00-1.91), and renal replacement therapy (RR, 0.52; 95%CrI, 0.18-1.18)]. The Bayesian analysis also showed that RenalGuard had a high probability of ranking first for all the secondary outcomes. These results were consistent in multiple sensitivity analyses. CONCLUSIONS: In patients undergoing percutaneous cardiovascular procedures, RenalGuard was associated with a reduced risk of CA-AKI and acute pulmonary edema compared with standard periprocedural hydration strategies.

Low- versus high-dose nitroglycerin infusion in the management of acute pulmonary edema.

BACKGROUND: Nitroglycerin (NTG) is commonly used for the management of pulmonary edema in acute heart failure presentations. Although commonly initiated at low infusion rates, higher infusion rates have favorable pharmacodynamic properties and may improve outcomes in the management of acute pulmonary edema. OBJECTIVES: To characterize the clinical outcomes including the time to resolution of severe hypertension when using an initial low dose (<100 µg/min) versus high-dose (≥100 µg/min) strategy. METHODS: This was a retrospective study performed at a single, tertiary academic emergency department in Atlanta, GA. We describe the blood pressure effects and key safety outcomes (intubation, hypotension, intensive care unit admissions) during the first hour of treatment of acute pulmonary edema. RESULTS: 41 patients were included in the final sample. 27 (66%) received low dose NTG and 14 (34%) received high dose NTG. The high dose group reached their blood pressure faster on average (hazard ratio = 3.5, 95% CI: 1.2-10.1). 8/14 (57%) of patients in the high dose group reached their BP target within the first hour of treatment, compared to 6/27 (22%) in the low dose group. Observed incidence of safety outcomes were similar between the two groups. CONCLUSIONS: Higher initial NTG doses may be an effective way to decrease times to achieve blood pressure targets and should be the focus of future trials.

The impact of renal artery stenting on therapeutic aims.

Renal artery stenosis manifests as poorly-controlled hypertension, impaired renal function or pulmonary oedema, therefore the success of treatment is dependent on indication. This study aims to determine the outcomes of patients undergoing renal artery stenting (RASt) based on therapeutic aim compared to criteria used in the largest randomised trial. Retrospective case-note review of patients undergoing RASt between 2008-2021 (n = 74). The cohort was stratified by indication for intervention (renal dysfunction, hypertension, pulmonary oedema) and criteria employed in the CORAL trial, with outcomes and adverse consequences reported. Intervention for hypertension achieved significant reduction in systolic blood pressure and antihypertensive agents at 1 year (median 43 mmHg, 1 drug), without detrimental impact on renal function. Intervention for renal dysfunction reduced serum creatinine by a median 124 µmol/L, sustained after 6 months. Intervention for pulmonary oedema was universally successful with significant reduction in SBP and serum creatinine sustained at 1 year. Patients who would have been excluded from the CORAL trial achieved greater reduction in serum creatinine than patients meeting the inclusion criteria, with equivalent blood pressure reduction. There were 2 procedure-related mortalities and 5 procedural complications requiring further intervention. 5 patients had reduction in renal function following intervention and 7 failed to achieve the intended therapeutic benefit. Renal artery stenting is effective in treating the indication for which it has been performed. Previous trials may have underestimated the clinical benefits by analysis of a heterogenous population undergoing a procedure rather than considering the indication, and excluding patients who would maximally benefit.