The safety of intravenous peripheral administration of 3% hypertonic saline: A systematic review and meta-analysis.

BACKGROUND: Three percent hypertonic saline (3% HTS) is used to treat several critical conditions such as severe and symptomatic hyponatremia and increased intracranial pressure. It has been traditionally administered through a central venous catheter (CVC). The avoidance of peripheral intravenous infusion of 3% HTS stems theoretically from the concern about the ability of the peripheral veins to tolerate hyperosmolar infusions. The aim of this systematic review and meta-analysis is to assess the rate of complications associated with the infusion of 3% HTS using peripheral intravenous access. METHODS: We conducted a systematic review and meta-analysis to assess the rate of complications related to the peripheral infusion of 3% HTS. We searched several databases for available studies that met the criteria until February 24th, 2022. We included ten studies conducted across three countries examining the incidence of infiltration, phlebitis, venous thrombosis, erythema, and edema. The overall event rate was calculated and transformed using the Freeman-Tukey arcsine method and pooled using the DerSimonian and Laird random-effects model. I2 was used to evaluate heterogeneity. Selected items from Newcastle-Ottawa Scale2 were used to assess the risk of bias in each included study. RESULTS: A total of 1200 patients were reported to have received peripheral infusion of 3% HTS. The analysis showed that peripherally administered 3% HTS has a low rate of complications. The overall incidence of each of the complications was as follows: infiltration 3.3%, (95% C.I. = 1.8-5.1%), phlebitis 6.2% (95% C.I. = 1.1-14.3%), erythema 2.3% (95% C.I. = 0.3-5.4%), edema 1.8% (95% C.I. = 0.0-6.2%), and venous thrombosis 1% (95% C.I. = 0.0-4.8%). There was one incident of venous thrombosis preceded by infiltration resulting from peripheral infusion of 3% HTS. CONCLUSIONS: Peripheral administration of 3% HTS is considered a safe and possibly preferred option as it carries a low risk of complications and is a less invasive procedure compared to CVC.

NaCl 3% Bolus Therapy as Emergency Treatment for Severe Hyponatremia: Comparison of 100 mL vs 250 mL.

CONTEXT: The aim of initial treatment of severe hyponatremia is to rapidly increase serum sodium to reduce the complications of cerebral edema. The optimal strategy to achieve this goal safely is still under debate. OBJECTIVE: To compare the efficacy and safety of 100 and 250 mL NaCl 3% rapid bolus therapy as initial treatment of severe hypotonic hyponatremia. METHODS: Retrospective analysis of patients admitted to a teaching hospital in The Netherlands between 2017 and 2019. The patients were 130 adults with severe hypotonic hyponatremia, defined as serum sodium ≤ 120 mmol/L. A bolus of either 100 mL (n = 63) or 250 mL (n = 67) NaCl 3% was the initial treatment. Successful treatment was defined as a rise in serum sodium ≥ 5 mmol/L within the first 4 hours after bolus therapy. Overcorrection of serum sodium was defined as an increase of more than 10 mmol/L in the first 24 hours. RESULTS: The percentage of patients with a rise in serum sodium ≥5 mmol/L within 4 hours was 32% and 52% after a bolus of 100 and 250 mL, respectively (P = .018). Overcorrection of serum sodium was observed after a median of 13 hours (range 9-17 hours) in 21% of patients in both treatment groups (P = .971). Osmotic demyelination syndrome did not occur. CONCLUSION: Initial treatment of severe hypotonic hyponatremia is more effective with a NaCl 3% bolus of 250 mL than of 100 mL and does not increase the risk of overcorrection.

Administration of 3% hypertonic saline via peripheral route: Is it really safe?

BACKGROUND: Administration of 3% sodiumchloride through a peripheral venous catheter is associated with risk of infusion-related adverse events (IRAE) due to its high osmolarity. Given this concern and the paucity of data regarding these events,many hospitals have policies that require central line administration of 3% sodiumchloride. OBJECTIVE: The objective of this analysis was to evaluate the incidence of IRAE associated with peripheral administration of 3% sodium chloride. METHODS: This analysis included patients who received 3% sodium chloride via a peripheral venous catheter between May 2017 and August 2019. The major endpoint of this analysiswas the overall incidence of IRAE, defined as the documentation of infiltration or phlebitis. Amultivariable logistic regression was performed to identify potential risk factors (e.g., age, infusion rate, infusion duration, peripheral venous catheter location, and needle gauge) for development of IRAE. RESULTS: A total of 706 administrations in 422 patientswere included. Seventy-four (10.5%) administrations were associated with a documented event. Based on the Infusion Nurses grading scale for infiltration or phlebitis, 48% of the events in this analysiswere grade 1 in severity. Duration of infusion of 3% sodiumchloride was found to be associated with an increased odds of an IRAE (OR per 1 h 1.02, 95% CI 1.01-1.02) in the multivariable analysis. Age, infusion rate, peripheral venous catheter location, and needle gauge were not independently associated with an increased risk of an IRAE. CONCLUSION: These data suggest that IRAE occurred more frequently when 3% sodium chloride was administered over a longer duration and themajority of events weremild with no permanent tissue injury. Itmay be reasonable to consider peripheral administration of 3% sodium chloride in the acute care setting for a short duration, although additional studies are needed to continue to evaluate its safety.

Efectividad del suero salino hipertónico nebulizado en pacientes con hipersecreción bronquial / Effectiveness of nebulized hypertonic saline in patients with bronchial hypersecretion

Introducción: El suero salino hipertónico (SSH) nebulizado mejora la calidad de vida y reduce las exacerbaciones en pacientes con fibrosis quística. Se desconoce si ofrecería los mismos beneficios en otras patologías hipersecretoras.MétodosEstudio observacional retrospectivo. Se incluyeron pacientes que superaron la prueba de tolerancia e iniciaron SSH al 5,8% con un año de seguimiento. Se cuantificaron parámetros clínicos y asistenciales en los años previo y posterior al inicio del tratamiento.ResultadosUn total de 101 pacientes, 60,4% mujeres, media de edad 65años (IC95%: 62,4-67,9): 82 (81,2%) bronquiectasias, 6 (5,9%) EPOC, 2 (2%) asma, 1 (1%) EPID y 10 (9,9%) otros. Se evidenció una reducción de la broncorrea (91,1% vs 75,2%), de las infecciones de repetición (57,4% vs 22,8%) y de los ciclos de antibioterapia (1,54 vs 0,55), así como un aumento del FEV1 (1.881ml vs 1.942ml) y una disminución de las asistencias a atención primaria (2,94 vs 1,1), de urgencias (0,36 vs 0,17) y de hospitalizaciones (0,17 vs 0,06). Setenta y tres pacientes (72,3%) presentaron una adecuada tolerancia.ConclusiónLa nebulización de SSH al 5,8% en pacientes con hipersecreción bronquial es segura y tiene un destacable impacto clínico y asistencial. (AU)

Introduction: Nebulized hypertonic saline (HS) improves quality of life and reduces exacerbations in patients with cystic fibrosis. It is unknown if it would offer the same benefits in other hypersecretory pathologies.MethodsRetrospective observational study. Patients who passed the tolerance test and started HS 5.8% with one year of follow-up were included. Clinical and healthcare parameters were quantified in the year before and after the start of treatment.Results101 patients, 60.4% women, 65years (95%CI: 62.4-67.9): 82 (81.2%) bronchiectasis, 6 (5.9%) COPD, 2 (2%) asthma, 1 (1%) ILD, and 10 (9.9%) other causes. There was a reduction in bronchorrhea (91.1% vs 75.2%), recurrent infections (57.4% vs 22.8%) and cycles of antibiotic therapy (1.54 vs 0.55), as well as an increase in FEV1 (1881ml vs. 1942ml) and a decrease in visits to primary care (2.94 vs. 1.1), emergencies (0.36 vs. 0.17) and hospitalizations (0.17 vs. 0.17). 06). 73 patients (72.3%) presented an adequate tolerance.ConclusionNebulization of HS 5.8% in patients with bronchial hypersecretion is safe and has a remarkable clinical and healthcare impact. (AU)

Patient-Specific Risk Factors Associated With the Development of Hyperchloremia in a Neurocritical Care Intensive Care Unit.

BACKGROUND: Hypertonic sodium chloride (HTS) is used in intensive care unit (ICU) settings to manage cerebral edema, intracranial hypertension, and for the treatment of severe hyponatremia. It has been associated with an increased incidence of hyperchloremia; however, there is limited literature focusing on hyperchloremic risk in neurologically injured patients. Objective: The primary objective of this study was to determine risk factors associated with development of hyperchloremia in a neurocritical care (NCC) ICU population. METHODS: This was a retrospective case-control study performed in an adult NCC ICU and included patients receiving HTS. The primary outcome was to evaluate patient characteristics and treatments associated with hyperchloremia. Secondary outcomes included acute kidney injury and mortality. RESULTS: Overall, 133 patients were identified; patients who were hyperchloremic were considered cases (n = 100) and patients without hyperchloremia were considered controls (n = 33). Characteristics and treatments were evaluated with univariate analysis and a logistic regression model. In the multivariate model, APACHE II Score, initial serum osmolality, total 3% saline volume, and total 23.4% saline volume were significant predictors for hyperchloremia. In addition, patients with a serum chloride greater than 113.5 mEq/L were found to have a higher risk of acute kidney injury (AKI) (adjusted OR 3.15; 95% CI 1.10-9.04). CONCLUSIONS: This study demonstrated APACHE II Score, initial serum osmolality, and total 3% and 23.4% saline volumes were associated with developing hyperchloremia in the NCC ICU. In addition, hyperchloremia is associated with an increased risk of AKI.

[Effectiveness of nebulized hypertonic saline in patients with bronchial hypersecretion]. / Efectividad del suero salino hipertónico nebulizado en pacientes con hipersecreción bronquial.

INTRODUCTION: Nebulized hypertonic saline (HS) improves quality of life and reduces exacerbations in patients with cystic fibrosis. It is unknown if it would offer the same benefits in other hypersecretory pathologies. METHODS: Retrospective observational study. Patients who passed the tolerance test and started HS 5.8% with one year of follow-up were included. Clinical and healthcare parameters were quantified in the year before and after the start of treatment. RESULTS: 101 patients, 60.4% women, 65years (95%CI: 62.4-67.9): 82 (81.2%) bronchiectasis, 6 (5.9%) COPD, 2 (2%) asthma, 1 (1%) ILD, and 10 (9.9%) other causes. There was a reduction in bronchorrhea (91.1% vs 75.2%), recurrent infections (57.4% vs 22.8%) and cycles of antibiotic therapy (1.54 vs 0.55), as well as an increase in FEV1 (1881ml vs. 1942ml) and a decrease in visits to primary care (2.94 vs. 1.1), emergencies (0.36 vs. 0.17) and hospitalizations (0.17 vs. 0.17). 06). 73 patients (72.3%) presented an adequate tolerance. CONCLUSION: Nebulization of HS 5.8% in patients with bronchial hypersecretion is safe and has a remarkable clinical and healthcare impact.

Hypertonic saline use in neurocritical care for treating cerebral edema: A review of optimal formulation, dosing, safety, administration and storage.

PURPOSE: Current Neurocritical Care Society guidelines on the management of cerebral edema recommend hypertonic saline (HTS) over mannitol in some scenarios, but practical questions remain regarding the appropriate administration method, concentration/dose, monitoring to ensure safe use, and storage. The aim of this article is to address these practical concerns based on the evidence currently available. SUMMARY: Many different hypertonic solutions have been studied to define the optimal hyperosmolar substance to relieve acute cerebral edema in patients with conditions such as acute ischemic stroke, intracerebral hemorrhage, subarachnoid hemorrhage, and traumatic brain injury. Mannitol and HTS are the main hyperosmolar therapies in use in contemporary neurocritical care practice. Contemporary use of HTS has followed a circuitous path in regards to the practical aspects of dosing and formulation, with evidence mainly consisting of retrospective or observational data. The effectiveness of bolus doses of HTS to lower acutely elevated intracranial pressure is well accepted. Adverse events with use of HTS are often mild and non-clinically significant if appropriate monitoring of serum sodium and chloride concentrations is performed. Available evidence shows that peripheral administration of HTS is likely safe in certain circumstances. Timely utilization of HTS is complicated by regulatory requirements for safe storage, but with appropriate safeguards HTS can be stored in patient care areas. CONCLUSION: HTS formulations, methods of administration, infusion rate, and storage vary by institution, and no practice standards exist. Central intravenous administration may be preferred for HTS, but peripheral intravenous administration is safe provided measures are undertaken to detect and prevent phlebitis and extravasation. The safe use of HTS is possible with proper protocols, education, and institutional safeguards in place.

Effect of continuous infusion of hypertonic saline solution on survival of patients with brain injury: a systematic review and meta-analysis.

BACKGROUND: The objective was to determine the effects of continuous infusion of hypertonic saline solutions on outcomes of patients with brain injury. METHODS: Preferred Reported Items for Systemic Reviews and Meta-Analysis guidelines were followed. We searched the MEDLINE and COCHRANE clinical trials register (through December 2021) and reference lists of articles. We included all clinical trials conducted in brain-injured patients hospitalized in intensive care units evaluating continuous infusion of hypertonic saline solution (osmolarity above 308 mOsm/L). Two reviewers extracted data that were checked by two others. The primary outcome was the in-hospital mortality rate. The main secondary outcomes were the rates of intracranial hypertension, an unfavorable neurological outcome at day 90, and adverse events. RESULTS: We identified 23 clinical trials reporting the use of continuous infusion of hypertonic saline solution in brain-injured patients. The primary outcome was available in 10 studies (n = 1883 patients). The odds ratio (OR) for in-hospital death with the intervention was 0.68 (95% confidence interval (CI), 0.54-0.85, I2 = 0%). In the subgroup of studies including only traumatic brain-injured patients (7 studies, n = 1521 patients), the OR for the primary outcome was 0.74 (95%CI 0.57-0.95) with the intervention. The OR for intracranial hypertension and unfavorable neurological outcome at day 90 were 0.66 (95%CI 0.49-0.88, I2 = 42%, n = 787 patients) and 0.61 (95%CI 0.46-0.81, I2 = 15%, n = 956 patients), respectively. Regarding safety, the OR of acute kidney injury and severe hypernatremia were 0.82 (95%CI 0.47-1.44, I2 = 0%) and 3.38 (95%CI 2.16-5.27, I2 = 24%). CONCLUSIONS: Continuous hypertonic saline solution infusion reduced in-hospital mortality without increasing the risk of unfavorable neurological outcome at day 90 in brain-injured patients hospitalized in intensive care units. Given the inclusion of observational and heterogeneous studies, further randomized studies are needed before developing recommendations for implementation at the bedside. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42021221367. Registered 13 May 2021.

Factors affecting prognosis of the patients with severe hyponatremia.

INTRODUCTION: Hyponatremia is one of the most common electrolyte abnormalities in clinical practice. Data regarding factors that have impact on mortality of severe hyponatremia and outcomes of its therapeutic management is insufficient. The present study aimed to examine the factors associated with mortality and the outcomes of treatment in patients with severe hyponatremia. MATERIALS AND METHODS: Patients with serum Na≤115mequiv./L who were admitted to Ordu State Hospital and Ordu University Training and Research Hospital between 2014 and 2018 were included in the study. Demographic and laboratory features, severity of the symptoms, comorbid diseases, medications, and clinical outcome measures of the patients were obtained retrospectively from their medical records. Factors associated with in-hospital mortality, overcorrection and undercorrection were assessed. RESULTS: A total of 145 patients (median age 69 years and 58.6% female) met inclusion criteria. Diuretic use was the most common etiologic factor for severe hyponatremia that present in 50 (34.5%) patients. Sixty-seven (46.2%) patients had moderately severe while 8 patients (5.5%) had severe symptoms. The median increase in serum Na 24h after admission in the study population was 8.9mequiv./L (-6 to 19). Nonoptimal correction was seen in 92 (63.4%) patients. Hypertonic saline use was associated with overcorrection (OR, 3.07; 95% CI: 1.47-6.39; p=0.002). Avoidance of hypertonic saline (aOR, 2.52; 95% CI: 1.12-5.66; p=0.029) and having neuropsychiatric disorder (aOR, 2.60; 95% CI: 1.10-6.11; p=0.025) were associated with undercorrection. In-hospital mortality rate was 12.4% and having CKD and cancer, undercorrection of sodium and presence of severe symptoms were significantly associated with in-hospital mortality. CONCLUSION: Severe hyponatremia in hospitalized patients is associated with substantial mortality. The incidence of non-optimal correction of serum Na is high; under-correction, presence of severe symptoms, chronic kidney disease and cancer were the factors that increase mortality rate.

Mannitol Is Comparable to Hypertonic Saline for Raised Intracranial Pressure in Acute Liver Failure (MAHAL Study): A Randomized Controlled Trial.

BACKGROUND: Raised intracranial pressure (ICP) due to cerebral edema (CE) is central to development of hepatic encephalopathy in acute liver failure (ALF). Mannitol (MT) and hypertonic saline (HS) have been shown to improve CE. We compared the efficacy and safety of the 2 modalities. METHODS: ALF with CE was prospectively randomized in an open study to receive either 5 mL/kg of either 3% HS, as continuous infusion; titrated every 6 hourly to achieve serum sodium of <160 (Group A; n = 26) or 1 g/kg of 20% MN as a IV bolus, repeated every 6 hourly (Group B; n = 25) in addition to standard ALF care. Primary end-point was reduction of ICP defined as optic nerve sheath diameter <5 mm and middle cerebral arterial pulsatility index <1.2 at 12 h. RESULTS: Fifty-one patients with ALF, hepatitis E being commonest (33.3%), median jaundice to HE interval of 8 (1-16) days, were randomized to HS (n = 26) or MN (n = 25). Baseline characteristics were comparable including King's college criteria (>2: 38.4% vs.40%). Overall, 61.5% patients in the HS and 56% in the MN group showed reduction in ICP at 12 h (p = 0.25). Rebound increase in ICP indices was noted in 5 (20%) patients in MT and none in HS (p < 0.05) group. New onset acute kidney injury was common in the MT group than in the HS group. The ICU stay and 28-day transplant-free survival were not different between the groups. CONCLUSIONS: While both agents had comparable efficacy in reducing ICP and mortality in ALF patients was comparable, HS was significantly better in preventing reducing rebound CE with lower renal dysfunction.

Efficacy and safety of hypertonic saline solutions fluid resuscitation on hypovolemic shock: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Fluid resuscitation is a fundamental intervention in patients with hypovolemic shock resulting from trauma. Appropriate fluid resuscitation in trauma patients could reduce organ failure, until blood components are available, and hemorrhage is controlled. We conducted a systematic review and meta-analysis assessing the effect of hypertonic saline/dextran or hypertonic saline for fluid resuscitation on patient outcomes restricted to adults with hypovolemic shock. METHODS: We conducted a search of electronic information sources, including PubMed, Embase, Web of Science, Cochrane library and bibliographic reference lists to identify all randomized controlled trials (RCTs) investigating outcomes of crystalloids versus colloids in patients with hypovolemic shock. We calculated the risk ratio (RR) or mean difference (MD) of groups using fixed or random-effect models. RESULTS: Fifteen studies including 3264 patients met our inclusion criteria. Survival to hospital discharge rate between research groups varied and amounted to 71.2% in hypertonic saline/dextran group vs. 68.4% for isotonic/normotonic fluid (normal saline) solutions (odds ratio [OR] = 1.19; 95% confidence interval [CI] 0.97-1.45; I2 = 48%; p = 0.09). 28- to 30-days survival rate for hypertonic fluid solutions was 72.8% survivable, while in the case of isotonic fluid (normal saline) - 71.4% (OR = 1.13; 95% CI 0.75-1.70; I2 = 43%; p = 0.56). CONCLUSIONS: This systematic review and meta-analysis, which included only evidence from RCTs hypertonic saline/dextran or hypertonic saline compared with isotonic fluid did not result in superior 28- to 30-day survival as well as in survival to hospital discharge. However, patients with hypotension who received resuscitation with hypertonic saline/dextran had less overall mortality as patients who received conventional fluid.

Safety of airway clearance combined with bronchodilator and hypertonic saline in non-hospitalized infants with acute bronchiolitis.

BACKGROUND: Acute viral bronchiolitis (AVB) is associated with significant morbidity and no study has addressed the safety of airway clearance techniques (ACT) for non-hospitalized infants. This study aimed to evaluate the safety of the use of ACT combined with bronchodilator and hypertonic saline in non-hospitalized children with the first episode of AVB. METHODS: A quasi-experimental study of infants aged 2-12 months, with a clinical diagnosis of AVB (mild to moderate), was performed. The Wang score, breathing frequency, oxygen saturation (SpO2), heart rate (HR), and the presence of adverse events were evaluated before, 10 and 20 min after the application of a protocol including ACT (nasal irrigation, prolonged slow expiration, and provoked cough), bronchodilator and hypertonic saline inhalation. A total of 265 infants, mean age 6.86±3.01 months, were included. RESULTS: A reduction (p<0.001) in the Wang score and in the breathing frequency as well as an increase in SpO2 were found. There was also a transient HR increment at 10 min followed by a reduction at 20 min (p<0.05). The proportion of patients presenting with chest retraction and wheezing decreased (p<0.001) after treatment. Most of the children (88.3%) did not experience adverse events. A post-treatment increment (p<0.001) of patients classified as having normal values, as well as a decrease in those with mild and moderate AVB, was found for the Wang score levels. CONCLUSION: The use of ACT combined with bronchodilator and hypertonic saline was safe, immediately after treatment, for non-hospitalized children with mild to moderate AVB. No clinically important deterioration or adverse events were identified in the follow-up period.

Safety and Efficacy of 23.4% Sodium Chloride Administered via Peripheral Venous Access for the Treatment of Cerebral Herniation and Intracranial Pressure Elevation.

BACKGROUND: Sodium chloride (NaCl) 23.4% solution has been shown to reduce intracranial pressure (ICP) and reverse transtentorial herniation. A limitation of 23.4% NaCl is its high osmolarity (8008 mOsm/l) and the concern for tissue injury or necrosis following extravasation when administered via peripheral venous access. The use of this agent is therefore often limited to central venous or intraosseous routes of administration. Our objective was to evaluate the safety and efficacy of administration of 23.4% NaCl via peripheral venous access compared with administration via central venous access. METHODS: We reviewed pharmacy records to identify all administrations of 23.4% NaCl at our institution between December 2017 and February 2020. Medical records were then reviewed to identify complications, such as extravasation, soft tissue injury or necrosis, hypotension (mean arterial pressure less than 65 mm Hg), pulmonary edema, hemolysis, and osmotic demyelination. We also compared the change in physiological variables, such as ICP, mean arterial pressure, cerebral perfusion pressure, and heart rate, as well as laboratory values, such as sodium, chloride, bicarbonate, creatinine, and hemoglobin, following administration of 23.4% NaCl via the peripheral and central venous routes. RESULTS: We identified 299 administrations of 23.4% NaCl (242 central and 57 peripheral) in 141 patients during the study period. There was no documented occurrence of soft tissue injury or necrosis in any patient. One patient developed hypotension following central administration. Among the 38 patients with ICP monitoring at the time of drug administration, there was no significant difference in median ICP reduction (- 13 mm Hg [central] vs. - 24 mm Hg [peripheral], p = 0.21) or cerebral perfusion pressure augmentation (16 mm Hg [central] vs. 15 mm Hg [peripheral], p = 0.87) based on route of administration. CONCLUSIONS: Peripheral venous administration of 23.4% NaCl is safe and achieves a reduction in ICP equivalent to that achieved by administration via central venous access.

Effect of Continuous Infusion of Hypertonic Saline vs Standard Care on 6-Month Neurological Outcomes in Patients With Traumatic Brain Injury: The COBI Randomized Clinical Trial.

Importance: Fluid therapy is an important component of care for patients with traumatic brain injury, but whether it modulates clinical outcomes remains unclear. Objective: To determine whether continuous infusion of hypertonic saline solution improves neurological outcome at 6 months in patients with traumatic brain injury. Design, Setting, and Participants: Multicenter randomized clinical trial conducted in 9 intensive care units in France, including 370 patients with moderate to severe traumatic brain injury who were recruited from October 2017 to August 2019. Follow-up was completed in February 2020. Interventions: Adult patients with moderate to severe traumatic brain injury were randomly assigned to receive continuous infusion of 20% hypertonic saline solution plus standard care (n = 185) or standard care alone (controls; n = 185). The 20% hypertonic saline solution was administered for 48 hours or longer if patients remained at risk of intracranial hypertension. Main Outcomes and Measures: The primary outcome was Extended Glasgow Outcome Scale (GOS-E) score (range, 1-8, with lower scores indicating worse functional outcome) at 6 months, obtained centrally by blinded assessors and analyzed with ordinal logistic regression adjusted for prespecified prognostic factors (with a common odds ratio [OR] >1.0 favoring intervention). There were 12 secondary outcomes measured at multiple time points, including development of intracranial hypertension and 6-month mortality. Results: Among 370 patients who were randomized (median age, 44 [interquartile range, 27-59] years; 77 [20.2%] women), 359 (97%) completed the trial. The adjusted common OR for the GOS-E score at 6 months was 1.02 (95% CI, 0.71-1.47; P = .92). Of the 12 secondary outcomes, 10 were not significantly different. Intracranial hypertension developed in 62 (33.7%) patients in the intervention group and 66 (36.3%) patients in the control group (absolute difference, -2.6% [95% CI, -12.3% to 7.2%]; OR, 0.80 [95% CI, 0.51-1.26]). There was no significant difference in 6-month mortality (29 [15.9%] in the intervention group vs 37 [20.8%] in the control group; absolute difference, -4.9% [95% CI, -12.8% to 3.1%]; hazard ratio, 0.79 [95% CI, 0.48-1.28]). Conclusions and Relevance: Among patients with moderate to severe traumatic brain injury, treatment with continuous infusion of 20% hypertonic saline compared with standard care did not result in a significantly better neurological status at 6 months. However, confidence intervals for the findings were wide, and the study may have had limited power to detect a clinically important difference. Trial Registration: ClinicalTrials.gov Identifier: NCT03143751.

Lidocaine coinfusion alleviates vascular pain induced by hypertonic saline infusion: a randomized, placebo-controlled trial.

BACKGROUND: Hypertonic saline solution has been frequently utilized in clinical practice. However, due to the nonphysiological osmolality, hypertonic saline infusion usually induces local vascular pain. We conducted this study to evaluate the effect of lidocaine coinfusion for alleviating vascular pain induced by hypertonic saline. METHODS: One hundred and six patients undergoing hypertonic saline volume preloading prior to spinal anesthesia were randomly allocated to two groups of 53 each. Group L received a 1 mg/kg lidocaine bolus followed by infusion of 2 mg/kg/h through the same IV line during hypertonic saline infusion; Group C received a bolus and infusion of normal saline of equivalent volume. Visual analogue scale (VAS) scores of vascular pain were recorded every 4 min. RESULTS: The vascular pain severity in Group L was significantly lower than that in Group C for each time slot (P < 0.05). The overall incidence of vascular pain during hypertonic saline infusion in Group L was 48.0%, which was significantly lower than the incidence (79.6%) in Group C (P < 0.05). CONCLUSION: Lidocaine coinfusion could effectively alleviate vascular pain induced by hypertonic saline infusion. TRIAL REGISTRATION: Chinese Clinical Trial Registry, number: ChiCTR1900023753 . Registered on 10 June 2019.

[Volume management: peri-operatively and peri-interventionally]. / Perioperatives und periinterventionelles Volumenmanagement.

Fluid therapy is one of the basic and most frequently performed medical therapies in everyday clinical practice. However, optimal volume management is a challenge: the application is simple, but the whole volume management is a complex process and physicians have to pay attention on underlying pathophysiology. Intravenous fluids should be prescribed like medications, i. e. the type of fluid and the amount must be adapted to each individual patient with his needs. Intravascular volume therapy is often used peri-operatively and peri-interventionally.Nowadays, crystalloid solutions are widely used and the standard is a balanced electrolyte solution. Only in selected situations 0,9 % sodium chloride solutions should be used, because they contain a high chloride concentration (154 mmol/l) and lead to increased risk of hyperchloremic metabolic acidosis.

Altered Corneal Epithelial Dendritic Cell Morphology and Phenotype Following Acute Exposure to Hyperosmolar Saline.

Purpose: The purpose of this study was to assess the morphological and phenotypic responses of corneal epithelial dendritic cells (DCs) to acute topical hyperosmolar stress, given a pathogenic role for tear hyperosmolarity in dry eye disease (DED). Methods: C57BL/6J mice were anesthetized and received 350 mOsm/L (physiological; n = 5 mice), 450 mOsm/L (n = 6), or 600 mOsm/L (n = 6) saline on a randomly assigned eye. Corneas were harvested 2 hours later. Immunofluorescent staining was performed using CD45, CD86, and CD68 antibodies to investigate DC morphology (density, viability, field area, circularity, and dendritic complexity) and immunological phenotype. Flow cytometry was used to confirm CD86 and CD68 expression in CD11c+ DCs, using C57BL/6J mice that received topical applications of 350 mOsm/L, 450 mOsm/L, or 600 mOsm/L (n = 5 per group) bilaterally for 2 hours. Results: Following exposure to 450 mOsm/L topical saline for 2 hours, DCs in the central and peripheral cornea were larger (field area: Pcentral = 0.005, Pperipheral = 0.037; circularity: Pcentral = 0.026, and Pperipheral = 0.013) and had higher expression of CD86 compared with 350 mOsm/L controls (immunofluorescence: P < 0.0001; flow cytometry: P = 0.0058). After application of 600 mOsm/L saline, DC morphology was unchanged, although the percentage of fragmented DCs, and phenotypic expression of CD86 (immunofluorescence: P < 0.0001; and flow cytometry: P = 0.003) and CD68 (immunofluorescence: P = 0.024) were higher compared to 350 mOsm/L controls. Conclusions: Short-term exposure to mild hyperosmolar saline (450 mOsm/L) induced morphological and phenotypic maturation in corneal epithelial DCs. More severe hyperosmolar insult (600 mOsm/L) for 2 hours appeared toxic to these cells. These data suggest that hyperosmolar conditions activate corneal DCs, which may have implications for understanding DC activation in DED.

Diagnostic value of the hypertonic saline bronchial provocation test in children with asthma using the high-power aerosol provocation system.

Objective: This study aimed to evaluate the diagnostic value of the modified hypertonic saline bronchial provocation test (HS-BPT) for children with asthma by using the high-power Aerosol Provocation System (APS).Methods: A total of 330 children suspected of having asthma and receiving HS-BPT-APS were included in this prospective survey conducted in Guangzhou, China from February 2017 to September 2018. The positive rate of HS-BPT-APS and the volume and types of adverse reactions were observed. There was also a retrospective cohort of 123 children with suspected asthma who underwent a methacholine BPT from 2015 to 2017. Using the method of nearest neighbor matching, a comparison was made of the positive rate and adverse reaction between the methacholine BPT group and HS-BPT-APS group.Results: The total positive rate of HS-BPT-APS was 43.9%. Common adverse reactions included cough, wheezing and chest tightness. There were no serious adverse reactions. Results of nearest neighbor matching showed a difference in the positive rate between the methacholine BPT group and HS-BPT-APS group (8.1% vs 18.2%, p = 0.026), but there was no statistically significant difference between the age groups in patients who received the methacholine BPT or HS-BPT-APS. There was a similar adverse reaction rate in the two groups (p = 0.609).Conclusions: HS-BPT-APS is simple, safe, and time-saving, with few adverse reactions. The positive rate of HS-BPT-APS was higher than that of methacholine BPT in children with asthma. HS-BPT-APS may be a valuable tool in the diagnosis of children with asthma, and further study is required.