Hypertonic saline and heart failure: "sodium-centric" or "chlorine-centric"?

Up to 50% of patients admitted for heart failure (HF) have congestion at discharge despite diagnostic and therapeutic advances. Both persistent congestion and diuretic resistance are associated with worse prognosis. The combination of hypertonic saline and loop diuretic has shown promising results in different studies. However, it has not yet achieved a standardized use, partly because of the great heterogeneity in the concentration of sodium chloride, the dose of diuretic or the amount of sodium in the diet. Classically, the movement of water from the intracellular space due to an increase in extracellular osmolarity has been postulated as the main mechanism involved. However, chloride deficit is postulated as the main up-regulator of plasma volume changes, and its correction may be the main mechanism involved. This "chloride centric" approach to heart failure opens the door to therapeutic strategies that would include diuretics to correct hypochloremia, as well as sodium free chloride supplementation.

Suspected cerebral salt wasting syndrome secondary to traumatic brain injury in a dog.

OBJECTIVE: To describe a dog with suspected cerebral salt wasting syndrome (CSWS) secondary to traumatic brain injury (TBI). CASE SUMMARY: A 2-month-old intact male Chihuahua-American Pitbull Terrier mix weighing 1.94 kg presented to a veterinary teaching emergency room after suffering bite wound-penetrating trauma to the head. Treatment was initiated with hyperosmotic agents, fluid resuscitation, and analgesia. The dog's neurologic dysfunction warranted hospitalization and continuous monitoring. Within 24 hours, the dog developed hyponatremia (133 mmol/L compared to 143 mmol/L on presentation [reference interval 142-149 mmol/L]). As the dog had concurrent tachycardia, increase in urine sodium concentration, polyuria, and weight loss, a diagnosis of cerebral salt wasting was suspected. A 2% hypertonic saline constant rate infusion was administered for volume replacement, and the patient showed improvement in clinical signs and blood sodium concentration. The dog was discharged on Day 5. Recheck examination showed significant neurologic improvement with sodium just below the low end of the reference range (141 mmol/L [reference interval 142-149 mmol/L]). NEW OR UNIQUE INFORMATION PROVIDED: This is the first description of suspected CSWS in veterinary medicine. Hyponatremia is a common finding in critically ill neurologic people, including those with TBI, and is typically associated with either syndrome of inappropriate antidiuretic hormone or CSWS. As treatment recommendations for syndrome of inappropriate antidiuretic hormone and CSWS are diametrically opposed, identifying the presence of hyponatremia and distinguishing between these 2 clinical entities is critical for improving patient care for those with TBI. This case highlights the characteristics and clinical progression regarding the diagnosis and management of suspected CSWS.

Comparison of mannitol and hypertonic saline solution for the treatment of suspected brain herniation during prehospital management of traumatic brain injury patients.

BACKGROUND AND IMPORTANCE: Occurrence of mydriasis during the prehospital management of traumatic brain injury (TBI) may suggest severe intracranial hypertension (ICH) subsequent to brain herniation. The initiation of hyperosmolar therapy to reduce ICH and brain herniation is recommended. Whether mannitol or hypertonic saline solution (HSS) should be preferred is unknown. OBJECTIVES: The objective of this study is to assess whether HSS, compared with mannitol, is associated with improved survival in adult trauma patients with TBI and mydriasis. DESIGN/SETTING AND PARTICIPANTS: A retrospective observational cohort study using the French Traumabase national registry to compare the ICU mortality of patients receiving either HSS or mannitol. Patients aged 16 years or older with moderate to severe TBI who presented with mydriasis during prehospital management were included. OUTCOME MEASURES AND ANALYSIS: We performed propensity score matching on a priori selected variables [i.e. age, sex and initial Coma Glasgow Scale (GCS)] with a ratio of 1 : 3 to ensure comparability between the two groups. The primary outcome was ICU mortality. The secondary outcomes were regression of pupillary abnormality during prehospital management, pulsatility index and diastolic velocity on transcranial Doppler within 24 h after TBI, early ICU mortality (within 48 h), ICU and hospital length of stay. RESULTS: Of 31 579 patients recorded in the registry between 2011 and 2021, 1417 presented with prehospital mydriasis and were included: 1172 (82.7%) received mannitol and 245 (17.3%) received HSS. After propensity score matching, 720 in the mannitol group matched 240 patients in the HSS group. Median age was 41 years [interquartile ranges (IQR) 26-60], 1058 were men (73%) and median GCS was 4 (IQR 3-6). No significant difference was observed in terms of characteristics and prehospital management between the two groups. ICU mortality was lower in the HSS group (45%) than in the mannitol group (54%) after matching [odds ratio (OR) 0.68 (0.5-0.9), P  = 0.014]. No differences were identified between the groups in terms of secondary outcomes. CONCLUSION: In this propensity-matched observational study, the prehospital osmotherapy with HSS in TBI patients with prehospital mydriasis was associated with a lower ICU mortality compared to osmotherapy with mannitol.

Hyperosmolar Therapy in Elderly Neurosurgical Patients: Comparison of the Effect of Mannitol (20%) and Hypertonic Saline (3%) on Advanced Cardiovascular Parameters Using Transesophageal Echocardiography: A Preliminary Randomized Controlled Trial.

OBJECTIVE: Osmotherapeutic agents increase the intravascular volume by withdrawing water from the brain followed by relative hypovolemia due to diuresis leading to significant changes in systemic hemodynamics which might have adverse consequences in the elderly. We studied the effect of mannitol (20%) and hypertonic saline (HTS) (3%) on left ventricular outflow tract velocity time integral (LVOT-VTI) and cardiac output (CO) in elderly patients undergoing supratentorial neurosurgical procedures using transesophageal echocardiography. METHODS: We recruited 28 patients aged above 65 years undergoing supratentorial craniotomy who received equiosmolar solutions of 5.35 ml/kg of 3% HTS (group HS, n = 14) or 5 ml/kg of 20% mannitol (group M, n = 14). LVOT-VTI was recorded at baseline, 15, 30, 45, 60, and 90 minutes postinfusion and CO was derived. We also recorded heart rate, blood pressure, fluid balance, brain relaxation, vasopressor use, complications, and neurological outcome. RESULTS: We found a significant decrease in LVOT-VTI at 45, and 60 minutes in group M as compared to group HS [mean (standard deviation), 16.76 (1.81) vs. 20.78 (1.87), P < 0.001, 17.4 (2.38) vs. 19.16 (2), P = 0.044, respectively]. We also found a corresponding significant fall in CO [3863.16 (845.87) vs. 4745.59 (1209.33) ml/minute, P = 0.034] and systolic blood pressure (P = 0.039), at 45 minutes in group M. Urine output was higher in group M (P < 0.001). All other parameters were comparable. CONCLUSIONS: HTS appears to be associated with better systemic hemodynamics (LVOT-VTI, CO) while providing equivalent brain relaxation as mannitol in elderly patients. A future larger study is required to confirm our preliminary findings.

Impact of resuscitation adjuncts on postintubation hypotension in patients with isolated traumatic brain injury.

INTRODUCTION: Postintubation hypotension (PIH) is a risk factor of endotracheal intubation (ETI) after injury. For those with traumatic brain injury (TBI), one episode of hypotension can potentiate that injury. This study aimed to identify the resuscitation adjuncts that may decrease the incidence of PIH in this patient population. METHODS: This is a 4-year (2019-2022) prospective observational study at a level I trauma center. Adult (18 years or older) patients with isolated TBI requiring ETI in the trauma bay were included. Blood pressures were measured 15 minutes preintubation and postintubation. Primary outcome was PIH, defined as a decrease in systolic blood pressure of ≥20% from baseline or to ≤80 mm Hg, or any decrease in mean arterial pressure to ≤60 mm Hg. Multivariable logistic regression was performed to identify the associations of preintubation vasopressor, hypertonic saline (HTS), packed red blood cell, and crystalloids on PIH incidence. RESULTS: Of the 490 enrolled patients, 16% had mild (head AIS, ≤2), 35% had moderate (head AIS, 3-4), and 49% had severe TBI (head AIS, ≥5). The mean ± SD age was 42 ± 22 years, and 71% were male. The median ISS, head AIS, and Glasgow Coma Scale were 26 (19-38), 4 (3-5), and 6 (3-11), respectively. The mean ± SD systolic blood pressure 15 minutes preintubation and postintubation were 118 ± 46 and 106 ± 45, respectively. Before intubation, 31% received HTS; 10%, vasopressors; 20%, crystalloids; and 14%, at least 1 U of packed red blood cell (median, 2 [1-2] U). Overall, 304 patients (62%) developed PIH. On multivariable regression analysis, preintubation use of vasopressors and HTS was associated with significantly decreased odds of PIH independent of TBI severity, 0.310 (0.102-0.944, p = 0.039) and 0.393 (0.219-0.70, p = 0.002), respectively. CONCLUSION: Nearly two thirds of isolated TBI patients developed PIH. Preintubation vasopressors and HTS are associated with a decreased incidence of PIH. Such adjuncts should be considered prior to ETI in patients with suspected TBI. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level III.

Comparative-effectiveness study evaluating outcomes for transforaminal epidural steroid injections performed with 3% hypertonic saline or normal saline in lumbosacral radicular pain.

BACKGROUND: Transforaminal epidural steroid injections (TFESI) are commonly employed to treat lumbosacral radiculopathy. Despite anti-inflammatory properties, the addition of 3% hypertonic saline has not been studied. OBJECTIVE: Compare the effectiveness of adding 0.9% NaCl (N-group) vs. 3% NaCl (H-group) in TFESI performed for lumbosacral radiculopathy. METHODS: This retrospective study compared TFESI performed with lidocaine, triamcinolone and 0.9% NaCl vs. lidocaine, triamcinolone and 3% NaCl. The primary outcome was the proportion of patients who experienced a ≥ 30% reduction in pain on a verbal rating scale (VRS; 0-100) at 3 months. Secondary outcome measures included the proportion of patients who improved by at least 30% for pain at 1 and 6 months, and who experienced ≥15% from baseline on the Oswestry disability index (ODI) at follow-up. RESULTS: The H-group experienced more successful pain outcomes than the N-group at 3 months (59.09% vs. 41.51%; P = .002) but not at 1 month (67.53% vs. 64.78%; P = .61) or 6 months (27.13% vs 21.55%: P = .31). For functional outcome, there was a higher proportion of responders in the H-group than the N-group at 3 months (70.31% vs. 53.46%; P = .002). Female, age ≤ 60 years, and duration of pain ≤ 6 months were associated with superior outcomes at the 3-month endpoint. Although those with a herniated disc experienced better outcomes in general with TFESI, the only difference favoring the H-group was for spondylolisthesis patients. CONCLUSIONS: 3% hypertonic saline is a viable alternative to normal saline as an adjunct for TFESI, with randomized studies needed to compare its effectiveness to steroids as a possible alternative. REGISTRATION: Thai Clinical Trials Registry ID TCTR 20231110006.

Hyperosmolar therapies for neurological deterioration in mild and moderate traumatic brain injury: towards new research.

The scoping review by Nicolò Marchesini and colleagues about the use of hyperosmolar therapies (HTs) in patients with traumatic brain injury (TBI) points out a significant gap in scientific literature regarding this topic. Although there are few high-quality recommendations, it is important to provide care under certain physiologic parameters. Through this letter we comment on the importance of guidelines to administer and monitor the use of HTs in the Neuro-ICU.

Severe Hypernatremia During Hydatid Cyst Surgery: An Anusual Cause Of Acute Abdomen.

Treatment of liver hydatid cysts is still in most cases surgical. To avoid the recurrence of hydatid cysts injection of scolicidal products inside the cystic cavity is an important step in the surgical procedure. Many scolicidal solutions are used. Hypertonic Saline Solution (HSS) is widely used by surgeons; however, there is a risk of hypertonic saline resorption and acute hypernatremia. Iatrogenic hypernatremia can be life-threatening. We report three cases of hypernatremia secondary to HSS injection for hydatid cyst disease treatment. The objective of this study was to discuss the clinical features, and treatment of this rare complication.

Effect of continuous hypertonic saline infusion on clinical outcomes in patients with traumatic brain injury.

Osmotic therapy has been recognized as an important treatment option for patients with traumatic brain injury (TBI). Nevertheless, the effect of hypertonic saline (HTS) remains unknown, as findings are primarily based on a large database. This study aimed to elucidate the effect of HTS on the clinical outcomes of patients with TBI admitted to the intensive care unit (ICU). We retrospectively identified patients with moderate-to-severe TBI from two public databases: Medical Information Mart for Intensive Care (MIMIC)-IV and eICU Collaborative Research Database (eICU-CRD). A marginal structural Cox model (MSCM) was used, with time-dependent variates designed to reflect exposure over time during ICU stay. Trajectory modeling based on the intracranial pressure evolution pattern allowed for the identification of subgroups. Overall, 130 (6.65%) of 1955 eligible patients underwent HTS. MSCM indicated that the HTS significantly associated with higher infection complications (e.g., urinary tract infection (HR 1.88, 95% CI 1.26-2.81, p = 0.002)) and increased ICU LOS (HR 2.02, 95% CI 1.71-2.40, p < 0.001). A protective effect of HTS on GCS was found in subgroups with medium and low intracranial pressure. Our study revealed no significant difference in mortality between patients who underwent HTS and those who did not. Increased occurrence rates of infection and electrolyte imbalance are inevitable outcomes of continuous HTS infusion. Although the study suggests slight beneficial effects, including better neurological outcomes, these results warrant further validation.

Hypertonic Saline Versus Other Intracranial-Pressure-Lowering Agents for Patients with Acute Traumatic Brain Injury: A Systematic Review and Meta-analysis.

Acute traumatic brain injury (TBI) is a major cause of mortality and disability worldwide. Intracranial pressure (ICP)-lowering is a critical management priority in patients with moderate to severe acute TBI. We aimed to evaluate the clinical efficacy and safety of hypertonic saline (HTS) versus other ICP-lowering agents in patients with TBI. We conducted a systematic search from 2000 onward for randomized controlled trials (RCTs) comparing HTS vs. other ICP-lowering agents in patients with TBI of all ages. The primary outcome was the Glasgow Outcome Scale (GOS) score at 6 months (PROSPERO CRD42022324370). Ten RCTs (760 patients) were included. Six RCTs were included in the quantitative analysis. There was no evidence of an effect of HTS on the GOS score (favorable vs. unfavorable) compared with other agents (risk ratio [RR] 0.82, 95% confidence interval [CI] 0.48-1.40; n = 406; 2 RCTs). There was no evidence of an effect of HTS on all-cause mortality (RR 0.96, 95% CI 0.60-1.55; n = 486; 5 RCTs) or total length of stay (RR 2.36, 95% CI - 0.53 to 5.25; n = 89; 3 RCTs). HTS was associated with adverse hypernatremia compared with other agents (RR 2.13, 95% CI 1.09-4.17; n = 386; 2 RCTs). The point estimate favored a reduction in uncontrolled ICP with HTS, but this was not statistically significant (RR 0.52, 95% CI 0.26-1.04; n = 423; 3 RCTs). Most included RCTs were at unclear or high risk of bias because of lack of blinding, incomplete outcome data, and selective reporting. We found no evidence of an effect of HTS on clinically important outcomes and that HTS is associated with adverse hypernatremia. The included evidence was of low to very low certainty, but ongoing RCTs may help to the reduce this uncertainty. In addition, heterogeneity in GOS score reporting reflects the need for a standardized TBI core outcome set.

Isotonic balanced fluid versus 0.9% saline in patients with moderate to severe traumatic brain injury: A double-blinded randomised controlled trial.

BACKGROUND AND IMPORTANCE: Traumatic brain injury (TBI) is a global health concern with significant economic impact. Optimal fluid therapy aims to restore intravascular volume, maintain cerebral perfusion pressure and blood flow, thus preventing secondary brain injury. While 0.9% saline (NS) is commonly used, concerns about acid-base and electrolyte imbalance and development of acute kidney injury (AKI) lead to consideration of balanced fluids as an alternative. OBJECTIVES: This study aimed to compare the outcomes of patients with moderate to severe TBI treated with Sterofundin (SF) versus NS. DESIGN, SETTINGS AND PARTICIPANTS: A double-blinded randomised controlled trial of patients aged 18 to 65 years with TBI was conducted at the University Malaya Medical Centre from February 2017 to November 2019. INTERVENTION OR EXPOSURE: Patients were randomly assigned to receive either NS or SF. The study fluids were administered for 72 h as continuous infusions or boluses. Participants, investigators, and staff were blinded to the fluid type. OUTCOMES MEASURE AND ANALYSIS: The primary outcome was in-hospital mortality. Relative risk (RR) with 95% confidence interval (CI) was calculated. MAIN RESULTS: A total of 70 patients were included in the analysis, with 38 in the NS group and 32 in the SF group. The in-hospital mortality rate were 3 (7.9%) in the NS group vs. 4 (12.5%) in the SF group, RR = 1.29 (95% CI, 0.64 to 2.59; p = 0.695). No patients developed AKI and required renal replacement therapy. ICP on day 3 was significantly higher in the SF group (18.60 ± 9.26) compared to 12.77 ± 3.63 in the NS group, (95% CI, -11.46 to 0.20; p = 0.037). There were no significant differences in 3-day biochemical parameters and cerebral perfusion pressure, ventilator-free days, length of ICU stay, or Glasgow Outcome Scale-Extended (GOS-E) score at 6 months. CONCLUSIONS: In patients with moderate to severe TBI, the use of SF was not associated with reduced in-hospital mortality, development of AKI, or improved 6-month GOS-E when compared to NS.

Comparison of 20% mannitol and 3% hypertonic saline for intraoperative brain relaxation during supratentorial brain tumour craniotomy in patients with a midline shift / Comparación entre manitol 20% y salino hipertónico 3% para la relajación cerebral intraoperatoria durante craneotomía por tumor cerebral supratentorial en pacientes con desviación de la línea media

Purpose of the study A prospective, randomized, double-blind study was designed to assess differences in brain relaxation between 20% mannitol and 3% hypertonic saline (HS) during elective supratentorial brain tumour surgery in patients with midline shift. Material and methods Sixty patients undergoing supratentorial craniotomy for tumour resection were enrolled to receive either 5mL/kg of 20% mannitol (n=30) or 3% HS (n=30) administered at skin incision. PCO2 in arterial blood was maintained within 35–40mmHg and arterial blood pressure was controlled within baseline values ±20%. The primary outcome was the proportion of satisfactory brain relaxation. The surgeon assessed brain relaxation on a four-point scale (1=excellent with no swelling, 2=minimal swelling, 3=serious swelling not requiring treatment, 4=severe swelling requiring treatment). Postsurgical intracranial changes determined by imaging techniques, postoperative complications, PACU and hospital stay, and mortality at 30 days were also recorded. Appropriate statistical tests were used for comparison; P<0.05 was considered as significant. This trial was registered in Eudract.ema.europa.eu (#2021-006290-40). Results There was no difference in brain relaxation: 2.00 [1.00–2.00] and 2.00 [1.75–3.00] for patients in mannitol and HS groups, respectively (P=0.804). Tumour size (OR: 0.99, 95% CI: 0.99–1.01; P=0.371), peritumoral oedema classification (OR: 0.57, 95% CI: 0.11–2.84; P=0.493), mass effect (OR: 0.86, 95% CI: 0.16–4.87; P=0.864), anaesthesia (OR: 4.88, 95% CI: 0.82–28.96; P=0.081) and midline shift (OR: 5.00, 95% CI: 0.84–29.70; P=0.077) did not have a significant influence on brain swelling in patients treated with either mannitol or HS. No significant differences in perioperative outcomes, mortality and length of PACU and hospital stay were observed (AU)

Objetivos del estudio Estudio prospectivo, aleatorizado y doble ciego diseñado para evaluar diferencias en la relajación cerebral entre manitol 20% y salino hipertónico (SH) 3% durante cirugía supratentorial electiva por tumor cerebral en pacientes con desviación de línea media. Material y métodos Sesenta pacientes sometidos a craneotomía supratentorial para resección tumoral se estudiaron para recibir 5ml/kg de manitol 20% (n=30) o SH 3% (n=30) administrados durante la incisión cutánea. La pCO2 en sangre arterial se mantuvo entre 35-40mmHg y la presión arterial se controló dentro de valores basales±20%. El objetivo principal fue la proporción de relajación cerebral satisfactoria. El cirujano evaluó la relajación cerebral en una escala de 4 puntos (1=excelente sin hinchazón, 2=hinchazón mínima, 3=hinchazón grave que no requiere tratamiento, 4=hinchazón severa que requiere tratamiento). Los cambios intracraneales posquirúrgicos determinados por técnicas de imagen, complicaciones postoperatorias, estancia en reanimación y hospitalaria, así como mortalidad a 30 días fueron registrados. Se usaron test estadísticos para la comparación, siendo considerado p<0,05 como significativo. El ensayo fue registrado en Eudract.ema.europa.eu (#2021-006290-40). Resultados No hubo diferencias en la relajación cerebral: 2,00 [1,00-2,00] y 2,00 [1,75-3,00] en los pacientes del grupo manitol y SH respectivamente (p=0,804). El tamaño tumoral (OR: 0,99: IC 95%:0,99-1,01; p=0,371), nivel de edema peritumoral (OR: 0,57; IC 95%:0,11-2,84; p=0,493), efecto masa (OR: 0,86; IC 95%: 0,16-4,87; p=0,864), anestesia empleada (OR: 4,88; 95% IC: 0,82-28,96; p=0,081) y desviación de la línea media (OR: 5,00; IC 95%: 0,84-29,70; p=0,077) no tuvieron influencia significativa sobre la hinchazón cerebral en los pacientes de ambos grupos. No hubo diferencias significativas en los resultados perioperatorios, mortalidad ni en estancia en reanimación ni hospitalaria (AU)

Nebuliser systems for drug delivery in cystic fibrosis.

BACKGROUND: Nebuliser systems are used to deliver medications to the lungs, to control the symptoms and the progression of lung disease in people with cystic fibrosis (CF). There are many different nebulised-medications prescribed for people with CF and there are many different types of nebuliser systems. Some of these nebulised medications are licenced for, and can be taken via only one type of nebuliser system; some are licensed for, and can be taken via more than one type of nebuliser system. This is an update to a previous systematic review. OBJECTIVES: To assess the time efficiency, effectiveness, safety, cost and impact of use (e.g. burden of care, adherence, quality of life (QoL)) of different nebuliser systems, when used with different inhaled medications for people with CF. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register comprising references identified from comprehensive electronic database searches, handsearching of relevant journals and abstract books containing conference proceedings. We searched the reference lists of each study for additional publications and approached the manufacturers of both nebuliser systems and nebulised medications for published and unpublished data. We also searched online trial registries. Date of the most recent search: 9 August 2023. SELECTION CRITERIA: Randomised controlled trials (RCTs) or quasi-RCTs comparing nebuliser systems, including conventional nebulisers, vibrating mesh technology (VMT) systems, adaptive aerosol delivery (AAD) systems and ultrasonic nebuliser systems. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed studies for inclusion. They also independently extracted data and assessed the risk of bias. A third review author assessed studies where agreement could not be reached. They assessed the certainty of the evidence using GRADE. MAIN RESULTS: The search identified 216 studies with 33 of these (2270 participants) included in the review. These studies compared the delivery of tobramycin, colistin, dornase alfa, hypertonic saline and other solutions through the different nebuliser systems in children and adults with CF. This review demonstrates variability in the delivery of medication depending on the nebuliser system used. The certainty of the evidence ranged from low to very low. Some conventional nebuliser systems providing higher flows, higher respirable fractions, and smaller particles decrease treatment time, increase deposition (the amount of drug reaching the lung), and may be preferred by people with CF, as compared to other conventional nebuliser systems providing lower flows, lower respirable fractions and larger particles. Newer nebuliser systems using AAD, or VMT (or both) reduce treatment time compared to conventional systems. Deposition (as a percentage of priming dose) with AAD is greater than with conventional systems. VMT systems may give greater deposition than conventional systems when measuring sputum levels. The available data indicate that these newer systems are safe when used with an appropriate priming dose, which may be different to the priming dose used for conventional systems. There is an indication that adherence is maintained or improved and that individuals prefer AAD or VMT systems, but also that some nebuliser systems using VMT may be subject to increased system failures. There is limited, unclear evidence on the impact of different nebuliser systems on lung function and a lack of data on the impact of different nebuliser systems on our outcomes of quality of life (QoL), adverse effects, respiratory exacerbations and related implications, adherence, satisfaction, cost and device reliability. AUTHORS' CONCLUSIONS: Newer technologies e.g. AAD and VMT have advantages over conventional systems in terms of treatment time, deposition as a percentage of priming dose, preference and adherence. Data are lacking for all varieties of medications which are used in CF care, including different inhaled antibiotics or hypertonic saline, with all delivery (nebuliser system) possibilities. Long-term RCTs are needed to evaluate different nebuliser systems to determine patient-focused outcomes (such as QoL and burden of care), safe and effective dosing levels of a wide variety of medications, clinical outcomes (such as hospitalisations and need for antibiotics), and an economic evaluation of their use. There are insufficient data to establish whether one nebuliser system is better than another overall. Clinicians should be aware of the variability in the performance of different nebuliser systems, compatibility with specific nebulised medication, and they must work with their patients to choose the best nebuliser system for each individual. This is likely to be an ongoing process as the needs and circumstances of each individual change over time.

Nebulised 3% hypertonic saline versus 0.9% saline for treating patients hospitalised with acute bronchiolitis: protocol for a randomised, double-blind, multicentre trial.

INTRODUCTION: Bronchiolitis is an acute viral infection of the lower respiratory tract. It is most commonly caused by respiratory syncytial virus. Being a common reason for hospitalisation, it affects 13-17% of all hospitalised children younger than 2 years. Only supportive therapy, including suctioning nasal secretions, water-electrolyte balance maintenance and oxygen supplementation when needed, is recommended. However, non-evidence-based diagnostic and therapeutic approaches, including the use of inhaled bronchodilators, nebulised epinephrine, and nebulised and systemic steroids, are common. The inhalation of 3% hypertonic saline is not recommended in bronchiolitis management. However, a recently published meta-analysis revealed that the inhalation of hypertonic saline can reduce the risk of hospitalisation for outpatients with bronchiolitis, while resulting in a shorter length of hospital stay and reduced severity of respiratory distress for inpatients, although the evidence is of low certainty. We aim to assess the efficacy of nebulised hypertonic saline for the treatment of children hospitalised with bronchiolitis. METHODS AND ANALYSIS: This will be a randomised, double-blinded, parallel-group, controlled trial. Children younger than 2 years who are hospitalised due to bronchiolitis will be recruited from at least three paediatric departments in Poland. Bronchiolitis is defined as an apparent viral respiratory tract infection associated with airway obstruction that is manifested by at least one of following symptoms: tachypnoea, increased respiratory effort, crackles and/or wheezing. A total of 140 children will be randomised (1:1) to receive either hypertonic saline nebulisation (5 mL, three times a day) or normal saline at the same dose. The primary outcome measure will be the duration of hospitalisation. ETHICS AND DISSEMINATION: The Bioethics Committee of the Lower Silesia Medical Chamber in Wroclaw approved the study protocol (4/PNDR/2023). Caregivers will receive oral and written information about the study and written informed consent will be obtained by the study physicians. The findings of the study will be submitted to a peer-reviewed journal, and abstracts will be submitted to relevant national and international conferences. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Registry (NCT06069336).

Methodological Aspects of Induced Sputum.

We aimed to conduct a state-of-the-art review of the current literature and offer further insights into the methodological aspects concerning induced sputum. The increasing popularity of sputum induction as a non-invasive and cost-effective method for obtaining lower airway secretions from patients who cannot produce sputum naturally has led to extensive research and applications in respiratory conditions like asthma and COPD. This technique allows for analysis of the cellular and biochemical components of the sputum to take place, providing insights into airway inflammation, immune cells, and help in predicting treatment response. Furthermore, induced sputum enables various analyses, including microRNA and gene expression studies and immunophenotyping. The procedure is generally safe and well tolerated, even in patients with airflow limitations; however, monitoring lung function is essential, especially in those with airway hyperresponsiveness. Optimal saline solution concentration and inhalation duration have been investigated, recommending a 15-20 min induction with hypertonic saline. Expectoration involves coughing at the end of each inhalation time. Careful handling during sputum processing is necessary for obtaining accurate results in cell cytology, immunocytochemistry, and in situ hybridization. Overall, induced sputum offers significant advantages as a preferred alternative for large-scale and repeated airway sampling, despite some technical demands and limitations.