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1.
Simultaneous Use of Hypertonic Saline and IV Furosemide for Fluid Overload: A Systematic Review and Meta-Analysis.
Liu, C, Peng, Z, Gao, X, Gajic, O, Dong, Y, Prokop, LJ, Murad, MH, Kashani, KB, Domecq, JP
Critical care medicine. 2021;(11):e1163-e1175
Abstract
OBJECTIVES To evaluate the efficacy of the simultaneous hypertonic saline solution and IV furosemide (HSS+Fx) for patients with fluid overload compared with IV furosemide alone (Fx). DATA SOURCES Electronic databases (MEDLINE, EMBASE, CENTRAL, Cochrane Database of Systematic Reviews, PsycINFO, Scopus, and WOS) were searched from inception to March 2020. STUDY SELECTION Randomized controlled trials on the use of HSS+Fx in adult patients with fluid overload versus Fx were included. DATA EXTRACTION Data were collected on all-cause mortality, hospital length of stay, heart failure-related readmission, along with inpatient weight loss, change of daily diuresis, serum creatinine, and 24-hour urine sodium excretion from prior to post intervention. Pooled analysis with random effects models yielded relative risk or mean difference with 95% CIs. DATA SYNTHESIS Eleven randomized controlled trials comprising 2,987 acute decompensated heart failure patients were included. Meta-analysis demonstrated that HSS+Fx was associated with lower all-cause mortality (relative risk, 0.55; 95% CI, 0.46-0.67; p < 0.05; I2 = 12%) and heart failure-related readmissions (relative risk, 0.50; 95% CI, 0.33-0.76; p < 0.05; I2 = 61%), shorter hospital length of stay (mean difference, -3.28 d; 95% CI, -4.14 to -2.43; p < 0.05; I2 = 93%), increased daily diuresis (mean difference, 583.87 mL; 95% CI, 504.92-662.81; p < 0.05; I2 = 76%), weight loss (mean difference, -1.76 kg; 95% CI, -2.52 to -1.00; p < 0.05; I2 = 57%), serum sodium change (mean difference, 6.89 mEq/L; 95% CI, 4.98-8.79; p < 0.05; I2 = 95%), and higher 24-hour urine sodium excretion (mean difference, 61.10 mEq; 95% CI, 51.47-70.73; p < 0.05; I2 = 95%), along with decreased serum creatinine (mean difference, -0.46 mg/dL; 95% CI, -0.51 to -0.41; p < 0.05; I2 = 89%) when compared with Fx. The Grading of Recommendation, Assessment, Development, and Evaluation certainty of evidence ranged from low to moderate. CONCLUSIONS Benefits of the HSS+Fx over Fx were observed across all examined outcomes in acute decompensated heart failure patients with fluid overload. There is at least moderate certainty that HSS+Fx is associated with a reduction in mortality in patients with acute decompensated heart failure. Factors associated with a successful HSS+Fx utilization are still unknown. Current evidence cannot be extrapolated to other than fluid overload states in acute decompensated heart failure.
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Treatment of symptomatic hyponatremia with hypertonic saline: a real-life observational study.
Chifu, I, Gerstl, A, Lengenfelder, B, Schmitt, D, Nagler, N, Fassnacht, M, Weismann, D
European journal of endocrinology. 2021;(5):647-655
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Abstract
OBJECTIVE Treatment of symptomatic hyponatremia is not well established. The European guidelines recommend bolus-wise administration of 150 mL of 3% hypertonic saline. This recommendation is, however, based on low level of evidence. DESIGN Observational study. METHODS Sixty-two consecutive hyponatremic patients admitted to the emergency department or intensive care unit of the University Hospital Wuerzburg were divided in subgroups according to treatment (150 mL bolus of 3% hypertonic saline or conventional treatment) and symptom severity. Treatment target was defined as an increase in serum sodium by 5-10 mEq/L within first 24 h and maximum 8 mEq/L during subsequent 24 h. RESULTS Thirty-three out of sixty-two patients (53%) were presented with moderate symptoms and 29/62 (47%) with severe symptoms. Thirty-six were treated with hypertonic saline and 26 conventionally. In the hypertonic saline group, serum sodium increased from 116 ± 7 to 123 ± 6 (24 h) and 127 ± 6 mEq/L (48 h) and from 121 ± 6 to 126 ± 5 and 129 ± 4 mEq/L in the conventional group, respectively. Overcorrection at 24 h occurred more frequent in patients with severe symptoms than with moderate symptoms (38% vs 6%, P < 0.05). Diuresis correlated positively with the degree of sodium overcorrection at 24 h (r = 0.6, P < 0.01). Conventional therapies exposed patients to higher degrees of sodium fluctuations and an increased risk for insufficient sodium correction at 24 h compared to hypertonic saline (RR: 2.8, 95% CI: 1.4-5.5). CONCLUSION Sodium increase was more constant with hypertonic saline, but overcorrection rate was high, especially in severely symptomatic patients. Reducing bolus-volume and reevaluation before repeating bolus infusion might prevent overcorrection. Symptoms caused by hypovolemia can be misinterpreted as severely symptomatic hyponatremia and diuresis should be monitored.
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Hypertonic saline in people with cystic fibrosis: review of comparative studies and clinical practice.
Terlizzi, V, Masi, E, Francalanci, M, Taccetti, G, Innocenti, D
Italian journal of pediatrics. 2021;(1):168
Abstract
Cystic fibrosis (CF) is a multisystem disorder, caused by mutations in the CF transmembrane conductance regulator (CFTR) gene. These cause a reduced secretion of chloride, a marked absorption of sodium and, therefore, of water, through the epithelium, resulting in the formation of thickened secretions in organs such as lung or pancreas. These viscous secretions lead to airway obstruction, chronic infection and inflammation resulting in progressive lung damage, bronchiectasis and eventual respiratory failure. Although the average life expectancy has increased over the last 30 years, lung disease is the most common cause of death in people with CF. For these reasons, the improvement of sputum clearance is a major therapeutic aim in CF and early initiation of airway clearance is widely recommended and implemented. Symptomatic mucolytic therapy today is mainly based on inhalation of DNase, hypertonic saline or mannitol, in combination with physiotherapy. Mucolytic agents break down the gel structure of mucus and therefore decrease its elasticity and viscosity, reducing the pulmonary exacerbation frequency and to improve and stabilize lung function. Nevertheless, high quality studies comparing these mucolytic drugs are still few, and the individual experiences of patients and caregivers explain the high variability of their use globally. This review will summarize the current knowledge on hypertonic saline in the treatment of CF lung disease. Furthermore, we report the real-world prescription of inhaled mucolytic agents in CF.
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Cellular dehydration acutely degrades mood mainly in women: a counterbalanced, crossover trial.
Suh, H, Lieberman, HR, Jansen, LT, Colburn, AT, Adams, JD, Seal, AD, Butts, CL, Kirkland, TM, Melander, O, Vanhaecke, T, et al
The British journal of nutrition. 2021;(10):1092-1100
Abstract
It is unclear if mild-to-moderate dehydration independently affects mood without confounders like heat exposure or exercise. This study examined the acute effect of cellular dehydration on mood. Forty-nine adults (55 % female, age 39 (sd 8) years) were assigned to counterbalanced, crossover trials. Intracellular dehydration was induced with 2-h (0·1 ml/kg per min) 3 % hypertonic saline (HYPER) infusion or 0·9 % isotonic saline (ISO) as a control. Plasma osmolality increased in HYPER (pre 285 (sd 3), post 305 (sd 4) mmol/kg; P < 0·05) but remained unchanged in ISO (pre 285 (sd 3), post 288 (sd 3) mmol/kg; P > 0·05). Mood was assessed with the short version of the Profile of Mood States Questionnaire (POMS). The POMS sub-scale (confusion-bewilderment, depression-dejection, fatigue-inertia) increased in HYPER compared with ISO (P < 0·05). Total mood disturbance score (TMD) assessed by POMS increased from 10·3 (sd 0·9) to 16·6 (sd 1·7) in HYPER (P < 0·01), but not in ISO (P > 0·05). When TMD was stratified by sex, the increase in the HYPER trial was significant in females (P < 0·01) but not in males (P > 0·05). Following infusion, thirst and copeptin (surrogate for vasopressin) were also higher in females than in males (21·3 (sd 2·0), 14·1 (sd 1·4) pmol/l; P < 0·01) during HYPER. In conclusion, cellular dehydration acutely degraded specific aspects of mood mainly in women. The mechanisms underlying sex differences may be related to elevated thirst and vasopressin.
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Pharmacologic Prophylaxis of Contrast-Induced Nephropathy.
Toso, A, Leoncini, M, Maioli, M, Bellandi, F
Interventional cardiology clinics. 2020;(3):369-383
Abstract
Different pharmacologic agents have been tested in the effort to prevent contrast-induced acute kidney injury (AKI) in the last two decades. To date, however, no individual drug has received unanimous approval for this aim. Since 2014 statins have been included as preventive treatment in the European guidelines for revascularization procedures in cardiac patients. The present update presents the latest findings in this field focusing on the changing paradigms in the definition and consequently the approach to nephroprotection that considers clinical prognosis as the major issue. We note the current shift from attention to contrast-induced AKI to contrast-associated AKI.
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What is the Role of Hyperosmolar Therapy in Hemispheric Stroke Patients?
Mohney, N, Alkhatib, O, Koch, S, O'Phelan, K, Merenda, A
Neurocritical care. 2020;(2):609-619
Abstract
The role of hyperosmolar therapy (HT) in large hemispheric ischemic or hemorrhagic strokes remains a controversial issue. Past and current stroke guidelines state that it represents a reasonable therapeutic measure for patients with either neurological deterioration or intracranial pressure (ICP) elevations documented by ICP monitoring. However, the lack of evidence for a clear effect of this therapy on radiological tissue shifts and clinical outcomes produces uncertainty with respect to the appropriateness of its implementation and duration in the context of radiological mass effect without clinical correlates of neurological decline or documented elevated ICP. In addition, limited data suggest a theoretical potential for harm from the prophylactic and protracted use of HT in the setting of large hemispheric lesions. HT exerts effects on parenchymal volume, cerebral blood volume and cerebral perfusion pressure which may ameliorate global ICP elevation and cerebral blood flow; nevertheless, it also holds theoretical potential for aggravating tissue shifts promoted by significant interhemispheric ICP gradients that may arise in the setting of a large unilateral supratentorial mass lesion. The purpose of this article is to review the literature in order to shed light on the effects of HT on brain tissue shifts and clinical outcome in the context of large hemispheric strokes, as well as elucidate when HT should be initiated and when it should be avoided.
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Management Strategies for Intracranial Pressure Crises in Subarachnoid Hemorrhage.
Ravishankar, N, Nuoman, R, Amuluru, K, El-Ghanem, M, Thulasi, V, Dangayach, NS, Lee, K, Al-Mufti, F
Journal of intensive care medicine. 2020;(3):211-218
Abstract
Objectives: Standard management strategies for lowering intracranial pressure (ICP) in traumatic brain injury has been well-studied, but the use of lesser known interventions for ICP in subarachnoid hemorrhage (SAH) remains elusive. Searches were performed in PubMed and EBSCO Host to identify best available evidence for evaluation and management of medically refractory ICP in SAH. The role of standard management strategies such as head elevation, hyperventilation, mannitol and hypertonic saline as well as lesser known management such as sodium bicarbonate, indomethacin, tromethamine, decompressive craniectomy, decompressive laparotomy, hypothermia, and barbiturate coma are reviewed. We also included dose concentrations, dose frequency, infusion volume, and infusion rate for these lesser known strategies. Nonetheless, there is still a gap in the evidence to recommend optimal dosing, timing and its role in the improvement of outcomes but early diagnosis and appropriate management reduce adverse outcomes.
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Nebulised hypertonic saline in moderate-to-severe bronchiolitis: a randomised clinical trial.
Jaquet-Pilloud, R, Verga, ME, Russo, M, Gehri, M, Pauchard, JY
Archives of disease in childhood. 2020;(3):236-240
Abstract
OBJECTIVES To investigate whether nebulised hypertonic saline (HS) treatment would decrease length of hospital stay (LOS) among infants with moderate-to severe-bronchiolitis compared with standard supportive care (SC). METHODS We conducted an open, multicentre, randomised clinical trial from 1 April 2013 to 31 March 2016, in Swiss children's hospitals. Patients aged 6 weeks to 24 months with a primary diagnosis of moderate or severe bronchiolitis were included. Children with previous episodes of wheezing, cardiac disease, chronic respiratory disease, immunodeficiency, prematurity (gestational age <34 weeks), corticotherapy in the preceding 2 weeks or inhaled bronchodilators within 24 hours before presentation were excluded. Patients were randomised to receive standard SC with nebulisation of 4 mL of 3% sodium chloride every 6 hours versus SSC. Main outcomes and measures were LOS duration of oxygen therapy, transfer to intensive care unit (ICU), readmission within 7 days following discharge and adverse events. RESULTS 121 children were randomised. No statistically significant differences were found between treatment groups at baseline (age, Wang Score, atopic history, smoking exposure). Children in the HS group had a non-significant difference in length of stay -2.8 hours (-10; 16) compared with the SC group. There were no differences in oxygen therapy duration, transfer to ICU, readmission rate or adverse events. The intervention was discontinued at the parents' request in 16% of the cases. CONCLUSION Our study does not support the use of HS nebulisation in children with moderate to severe bronchiolitis. TRIAL REGISTRATION NUMBER NCT01812525.
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A quadruple blind, randomised controlled trial of gargling agents in reducing intraoral viral load among hospitalised COVID-19 patients: A structured summary of a study protocol for a randomised controlled trial.
Khan, FR, Kazmi, SMR, Iqbal, NT, Iqbal, J, Ali, ST, Abbas, SA
Trials. 2020;(1):785
Abstract
OBJECTIVES 1- To compare the effectiveness of 1% Hydrogen peroxide, 0.2% Povidone-Iodine, 2% hypertonic saline and a novel solution Neem extract (Azardirachta indica) in reducing intra-oral viral load in COVID-19 positive patients. 2- To determine the salivary cytokine profiles of IL-2, IL-4, IL-6, IL-10, TNF-α, IFN-γ and IL- 17 among COVID-19 patients subjected to 1% Hydrogen peroxide, 0.2% Povidone-Iodine, 2% hypertonic saline or Neem extract (Azardirachta indica) based gargles. TRIAL DESIGN This will be a parallel group, quadruple blind-randomised controlled pilot trial with an add on laboratory based study. PARTICIPANTS A non-probability, purposive sampling technique will be followed to identify participants for this study. The clinical trial will be carried out at the Aga Khan University Hospital (AKUH), Karachi, Pakistan. The viral PCR tests will be done at main AKUH clinical laboratories whereas the immunological tests (cytokine analysis) will be done at the Juma research laboratory of AKUH. The inclusion criteria are laboratory-confirmed COVID-19 positive patients, male or female, in the age range of 18-65 years, with mild to moderate disease, already admitted to the AKUH. Subjects with low Glasgow coma score, with a history of radiotherapy or chemotherapy, who are more than 7 days past the onset of COVID- 19 symptoms, or intubated or edentulous patients will be excluded. Patients who are being treated with any form of oral or parenteral antiviral therapy will be excluded, as well as patients with known pre-existing chronic mucosal lesions such as lichen planus. INTERVENTION AND COMPARATOR Group A (n=10) patients on 10 ml gargle and nasal lavage using 0.2% Povidone-Iodine (Betadiene® by Aviro Health Inc./ Pyodine® by Brooks Pharma Inc.) for 20-30 seconds, thrice daily for 6 days. Group B (n=10) patients will be subjected to 10 ml gargle and nasal lavage using 1% Hydrogen peroxide (HP® by Karachi Chemicals Products Inc./ ActiveOxy® by Boumatic Inc.) for 20-30 seconds, thrice daily for 6 days. Group C will comprised of (n=10) subjects on 10ml gargle and nasal lavage using Neem extract solution (Azardirachta indica) formulated by Karachi University (chemistry department laboratories) for 20-30 seconds, thrice daily for 6 days. Group D (n=10) patients will use 2% hypertonic saline (Plabottle® by Otsuka Inc.) gargle and nasal lavage for a similar time period. Group E (n=10) will serve as positive controls. These will be given simple distilled water gargles and nasal lavage for 20-30 seconds, thrice daily for six days. For nasal lavage, a special douche syringe will be provided to each participant. Its use will be thoroughly explained by the data collection officer. After each use, the patient is asked not to eat, drink, or rinse their mouth for the next 30 minutes. MAIN OUTCOMES The primary outcome is the reduction in the intra-oral viral load confirmed with real time quantitative PCR. RANDOMISATION The assignment to the study group/ allocation will be done using the sealed envelope method under the supervision of Clinical Trial Unit (CTU) of Aga Khan University, Karachi, Pakistan. The patients will be randomised to their respective study group (1:1:1:1:1 allocation ratio) immediately after the eligibility assessment and consent administration is done. BLINDING (MASKING): The study will be quadruple-blinded. Patients, intervention provider, outcome assessor and the data collection officer will be blinded. The groups will be labelled as A, B, C, D or E. The codes of the intervention will be kept in lock & key at the CTU and will only be revealed at the end of study or if the study is terminated prematurely. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): As there is no prior work on this research question, so no assumptions for the sample size calculation could be made. The present study will serve as a pilot trial. We intend to study 50 patients in five study groups with 10 patients in each study group. For details, please refer to Fig. 1 for details. TRIAL STATUS Protocol version is 7.0, approved by the department and institutional ethics committees and clinical trial unit of the university hospital. Recruitment is planned to start as soon as the funding is sanctioned. The total duration of the study is expected to be 6 months i.e. August 2020-January 2021. TRIAL REGISTRATION This study protocol was registered at www.clinicaltrials.gov on 10 April 2020 NCT04341688 . FULL PROTOCOL The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol. The study protocol has been reported in accordance with the Standard Protocol Items: Recommendations for Clinical Interventional Trials (SPIRIT) guidelines (Additional file 2). Fig. 1 Flow diagram of study-participants' timeline.
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A four week trial of hypertonic saline in children with mild cystic fibrosis lung disease: Effect on mucociliary clearance and clinical outcomes.
Donaldson, SH, Danielle Samulski, T, LaFave, C, Zeman, K, Wu, J, Trimble, A, Ceppe, A, Bennett, WD, Davis, SD
Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society. 2020;(6):942-948
Abstract
BACKGROUND Hypertonic saline (HS) is commonly prescribed for children with cystic fibrosis (CF) despite the absence of strong data indicating clinical efficacy in a population with mild lung disease. We hypothesized that HS treatment would result in a sustained improvement in mucociliary clearance (MCC) in children with CF who had minimal lung disease, thus providing evidence for a biologically relevant effect that also may be associated with clinical improvements. METHODS We performed a randomized, placebo controlled, double blind study of 6% versus 0.12% sodium chloride, delivered three-times daily with an eFlow nebulizer for 4 weeks. MCC was measured using gamma scintigraphy at baseline, 2-hours after the first study treatment, and ~12-hours after the final dose (at day 28). Spirometry, respiratory symptoms (CFQ-R), and safety were also assessed. RESULTS Study treatments were generally well tolerated and safe. HS (6% sodium chloride) resulted in a significant, sustained improvement from baseline in whole lung clearance after 4 weeks of therapy (p = 0.014), despite absence of a prolonged single-dose effect after the initial dose. This sustained change (12 hrs after prior dose) was significantly greater when compared to placebo (0.12% sodium chloride) treatment (p = 0.016). Improvements in spirometry with HS did not reach statistical significance but correlated with MCC changes. CONCLUSIONS The observed sustained improvement in MCC with HS suggests that this treatment may yield health benefits, even in relatively mildly affected children with CF. Highlighting this physiologic finding is important due to the lack of meaningful, validated endpoints in this population.