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.

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.

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.

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.

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.

Standardized Volume Dosing Protocol of 23.4% Hypertonic Saline for Pediatric Critical Care: Initial Experience.

Background: Standardized volume dosing of 23.4% hypertonic saline (HTS) exists for adults, but the concentration, dosing and administration of HTS in pediatrics is variable. With emerging pediatric experience of 23.4% HTS, a standard volume dose approach may be helpful. Objective: To describe initial experience with a standardized 23.4% HTS weight-based volume dosing protocol of 10, 20, or 30 mL in the pediatric intensive care unit. Methods: Standard volume doses of 23.4% HTS were developed from weight dosing equivalents of 3% HTS. Pre and post sodium and intracranial pressure (ICP) measurements were compared with paired t-test or Wilcoxon rank-sum test. The site of administration and complications were noted. Results: A total of 16 pediatric patients received 37 doses of 23.4% HTS, with the smallest patient weighing 11 kg. For protocol compliance, 17 doses (46%) followed recommended dosing, 19 were less volume than recommended (51%), and 1 dose (3%) was more than recommended. Mean increase in sodium was 3.5 mEq/L (95% CI = 2-5 mEq/L); P < 0.0001. The median decrease in ICP was 10.5 mm Hg (interquartile range [IQR] 8.3-19.5) for a 37% (IQR 25%-64%) reduction. Most doses were administered through central venous access, although peripheral intravenous administrations occurred in 4 patients without complication. Conclusion and Relevance: Three standard-volume dose options of 23.4% HTS based on weight increases sodium and reduces ICP in pediatric patients. Standard-volume doses may simplify weight-based dosing, storage and administration for pediatric emergencies, although the optimum dose, and safety of 23.4% HTS in children remains unknown.

Fluid Overload in Pediatric Severe Traumatic Brain Injury.

OBJECTIVE: Pediatric traumatic brain injury is a major public health problem in the United States. Hypertonic saline therapy is a well-established treatment in patients with severe traumatic brain injury (Glasgow Coma Scale ≤ 8) who have intracranial hypertension. In children, fluid overload is associated with increased mortality, ventilator duration, and length of PICU stay, even when controlling for severity of illness. This study reports prevalence of fluid overload in pediatric patients with severe traumatic brain injury treated with 3% hypertonic saline and effect on clinical outcomes. DESIGN: Single-center retrospective chart review. SETTING: PICUs at two tertiary children's hospitals. PATIENTS: One hundred thirty-eight patients with traumatic brain injury with postresuscitation Glasgow Coma Scale less than or equal to 8 who received hypertonic saline from September 1, 2010, to February 28, 2016, and intracranial pressure monitoring and survived at least 24 hours from admission. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We used fluid balance percentage greater than or equal to 10% as our definition of fluid overload. Ninety-one percent of patients less than 1 year old had fluid overload on day 10 of admission compared with 47% of patients greater than 1 year. Fluid overloaded patients did not have increased mortality, acute kidney injury, PICU length of stay, or ventilator days. Hypertonic saline was not the cause of fluid overload in these patients. CONCLUSIONS: Patients with severe traumatic brain injury do have high rates of fluid overload. However, fluid overload did not contribute to mortality, longer days on the ventilator, increased risk of acute kidney injury, or increased PICU length of stay.

Muscle pain induced by hypertonic saline in the knee extensors decreases single-limb isometric time to task failure.

PURPOSE: Increased nociceptive activity and the experience of exercise-induced pain (EIP) may contribute to fatigue during endurance exercise. To investigate this, a pain model that produces pain similar to EIP and decouples its relationship to exercise intensity is required. This study (1) compared the quality of pain caused by a hypertonic saline injection into the vastus lateralis in resting and exercise conditions, and (2) investigated whether this pain contributes to changes in time to task failure. METHODS: On separate days, 18 participants completed a time to task failure at 20% maximal voluntary torque (MVT), a resting hypertonic saline intramuscular injection, and in a further three visits a time to task failure at 10% MVT following injection of isotonic saline, hypertonic saline or a control (no injection). RESULTS: In a subset of eligible participants (n = 12), the hypertonic saline combined with 10% MVT produced a qualitative experience of pain (assessed by the McGill Pain Questionnaire) that felt similar to EIP. 10% MVT with hypertonic saline significantly elevated pain intensity in the first 20% of the time to task failure and caused a significantly (P < 0.05) shorter time to task failure (448 ± 240 s) compared with the isotonic saline (605 ± 285 s) and control (514 ± 197 s) conditions. CONCLUSION: These findings demonstrate that hypertonic saline increases the intensity of pain during exercise, which results in a faster occurrence of exercise-induced fatigue. These results provide important evidence supporting pain as a limiting factor in endurance performance.

Osmotherapy for malignant cerebral edema in a phase 2 prospective, double blind, randomized, placebo-controlled study of IV glibenclamide.

BACKGROUND/OBJECTIVE: Malignant edema can be a life-threatening complication of large hemispheric infarction (LHI), and is often treated with osmotherapy. In this exploratory analysis of data from the GAMES-RP study, we hypothesized that patients receiving osmotherapy had symptomatic cerebral edema, and that treatment with intravenous (IV) glibenclamide would modify osmotherapy use as compared with placebo. METHODS: GAMES-RP was a phase 2 multi-center prospective, double blind, randomized, placebo-controlled study in LHI. Patients were randomized to IV glibenclamide (e.g. IV glyburide) or placebo. Cerebral edema therapies included osmotherapy and/or decompressive craniectomy at the discretion of the treating team. Total bolus osmotherapy dosing was quantified by "osmolar load". Radiographic edema was defined by dichotomizing midline shift at 24 h. Clinical changes were defined as any increase in NIHSS1a. RESULTS: Osmotherapy was administered to 40 of the 77 patients at a median of 39 [27-55] h after stroke onset. The median baseline DWI lesion volume was significantly larger in the osmotherapy treated group (167 [146-211] mL v. 139 [112-170] mL; P=0.046). Adjudicated malignant edema (75% v. 16%; P<0.001) was more common in the osmotherapy treated group. There were no differences in the proportion of patients receiving osmotherapy or the median total osmolar load between treatment arms. Most patients (76%) had a decrease in consciousness (NIHSS item 1A ≥1) on the day they began receiving osmotherapy. CONCLUSIONS: In the GAMES-RP trial, osmolar therapies were most often administered in response to clinical symptoms of decreased consciousness. However, the optimal timing of administration and impact on outcome after LHI have yet to be defined.

Efficacy, Effectiveness, Safety, and Cost-effectiveness of Epidural Adhesiolysis for Treating Failed Back Surgery Syndrome. A Systematic Review.

BACKGROUND: Failed back surgery syndrome (FBSS) has a profound impact on patients' quality of life and represents a major clinical challenge and a significant economic burden for society. Adhesiolysis is used as a treatment to eliminate perineural/epidural adhesions in patients with chronic pain attributed to FBSS. OBJECTIVE: To evaluate the efficacy, effectiveness, safety, and cost-effectiveness of epidural adhesiolysis compared with other procedures for treating FBSS. METHOD: A systematic review was conducted. The electronic databases Medline/PreMedline, EMBASE, Cochrane Library Plus, Centre for Reviews and Dissemination databases, SCOPUS, Science Citation Index, and PEDRO were consulted through April 2017. Predefined criteria were used to determine inclusion of the studies and to assess their methodological quality. RESULTS: Ten reports were included. No randomized controlled trials (RCTs) on efficacy or cost-effectiveness were found. Three reports (corresponding to two RCTs, N = 212) suggested that adhesiolysis was effective, especially for pain and disability. However, both studies presented serious methodological flaws. In addition to RCTs, seven observational studies with high risk of bias reported data on effectiveness and safety. Fifty-eight adverse events were reported among 130 patients undergoing endoscopic adhesiolysis, and 19 among the 110 undergoing percutaneous adhesiolysis. CONCLUSIONS: The evidence on the efficacy and cost-effectiveness of adhesiolysis for treating FBSS is nonexistent, whereas evidence on its effectiveness and safety is insufficient. Incorporating data from observational studies did not improve the quality of the evidence on effectiveness.

Hypertonic Saline in Human Sepsis: A Systematic Review of Randomized Controlled Trials.

The role of hypertonic saline in sepsis remains unclear because clinical data are limited and the balance between beneficial and adverse effects is not well defined. In this systematic literature review, we searched PubMed and Embase to identify all randomized controlled trials up until January 31, 2018 in which hypertonic saline solutions of any concentration were used in patients of all ages with sepsis and compared to a cohort of patients receiving an isotonic fluid. We identified 8 randomized controlled trials with 381 patients who had received hypertonic saline. Lower volumes of hypertonic saline than of isotonic solutions were needed to achieve the desired hemodynamic goals (standardized mean difference, -0.702; 95% CI, -1.066 to -0.337; P < .001; moderate-quality evidence). Hypertonic saline administration was associated with a transient increase in sodium and chloride concentrations without adverse effects on renal function (moderate-quality evidence). Some data suggested a beneficial effect of hypertonic saline solutions on some hemodynamic parameters and the immunomodulatory profile (very low-quality evidence). Mortality rates were not significantly different with hypertonic saline than with other fluids (odds ratio, 0.946; 95% CI, 0.688-1.301; P = .733; low-quality evidence). In conclusion, in our meta-analysis of studies in patients with sepsis, hypertonic saline reduced the volume of fluid needed to achieve the same hemodynamic targets but did not affect survival.

Effect of 3% saline and furosemide on biomarkers of kidney injury and renal tubular function and GFR in healthy subjects - a randomized controlled trial.

BACKGROUND: Chloride is speculated to have nephrotoxic properties. In healthy subjects we tested the hypothesis that acute chloride loading with 3% saline would induce kidney injury, which could be prevented with the loop-diuretic furosemide. METHODS: The study was designed as a randomized, placebo-controlled, crossover study. Subjects were given 3% saline accompanied by either placebo or furosemide. Before, during and after infusion of 3% saline we measured glomerular filtration rate (GFR), fractional excretion of sodium (FENa), urinary chloride excretion (u-Cl), urinary excretions of aquaporin-2 (u-AQP2) and epithelial sodium channels (u-ENaCγ), neutrophil gelatinase-associated lipocalin (u-NGAL) and kidney injury molecule-1 (u-KIM-1) as marker of kidney injury and vasoactive hormones: renin (PRC), angiotensin II (p-AngII), aldosterone (p-Aldo) and arginine vasopressin (p-AVP). Four days prior to each of the two examinations subjects were given a standardized fluid and diet intake. RESULTS: After 3% saline infusion u-NGAL and KIM-1 excretion increased slightly (u-NGAL: 17 ± 24 during placebo vs. -7 ± 23 ng/min during furosemide, p = 0.039, u-KIM-1: 0.21 ± 0.23 vs - 0.06 ± 0.14 ng/ml, p <  0.001). The increase in u-NGAL was absent when furosemide was given simultaneously, and the responses in u-NGAL were not significantly different from placebo control. Furosemide changed responses in u-KIM-1 where a delayed increase was observed. GFR was increased by 3% saline but decreased when furosemide accompanied the infusion. U-Na, FENa, u-Cl, and u-osmolality increased in response to saline, and the increase was markedly pronounced when furosemide was added. FEK decreased slightly during 3% saline infusion, but simultaneously furosemide increased FEK. U-AQP2 increased after 3% saline and placebo, and the response was further increased by furosemide. U-ENaCγ decreased to the same extent after 3% saline infusion in the two groups. 3% saline significantly reduced PRC, p-AngII and p-Aldo, and responses were attenuated by furosemide. p-AVP was increased by 3% saline, with a larger increase during furosemide. CONCLUSION: This study shows minor increases in markers of kidney injury after 3% saline infusion Furosemide abolished the increase in NGAL and postponed the increase in u-KIM-1. The clinical importance of these findings needs further investigation. TRIAL REGISTRATION: (EU Clinical trials register number: 2015-002585-23 , registered on 5th November 2015).

Incidence of Adverse Events During Peripheral Administration of Sodium Chloride 3.

PURPOSE: Traditionally, sodium chloride 3% has been administered via a central venous line (CVL) because of the perceived risk of infiltration and tissue injury due to its high osmolarity. In clinical practice, sodium chloride 3% is commonly administered through peripheral venous catheters (PVCs) given the necessity of timely administration. However, there is no published data on the safety of administering sodium chloride 3% through PVCs in the adult population. The objective of this study was to evaluate the safety of peripheral venous administration of sodium chloride 3%. MATERIALS AND METHODS: A retrospective review was conducted in patients who received sodium chloride 3% in the intensive care unit (ICU). Patients were excluded if they had a CVL for the entire duration of the infusion or younger than 18 years at the time of administration. Baseline patient and infusion characteristics were collected. Infusion-related adverse events (IRAEs) were recorded, graded, and interventions required were noted. RESULTS: A total of 66 patients were included in the analysis. The most common indication was hyponatremia and majority of the patients were managed in the neurosurgical ICU. The most common risk factor for IRAEs was the presence of altered mental status. Four patients experienced an IRAE at an event rate of 6.1%. Patients who experienced an IRAE ranged from 38 to 82 years old. The IRAEs were grade 1 in severity, managed conservatively with removal of the PVC, and 2 of the 4 patients had their infusions restarted peripherally. The time to initial IRAE ranged from 2 to 94 hours. For the entire cohort, hospital and ICU length of stay were 8 and 4 days, respectively. CONCLUSIONS: The rate of IRAEs related to the infusion of sodium chloride 3% through PVCs appears to be similar to those reported with other hyperosmotic agents and could be considered for patients who need time-sensitive therapy.

Effect of Hyperosmolar Therapy on Outcome Following Spontaneous Intracerebral Hemorrhage: Ethnic/Racial Variations of Intracerebral Hemorrhage (ERICH) Study.

PURPOSE: We aimed to identify the effect of hyperosmolar therapy (mannitol and hypertonic saline) on outcomes after intracerebral hemorrhage (ICH) in the Ethnic/Racial Variations of Intracerebral Hemorrhage (ERICH) study. METHODS: Comparison of ICH cases treated with hyperosmolar therapy versus untreated cases was performed using a propensity score based on age, initial Glasgow Coma Scale, location of ICH (lobar, deep, brainstem, and cerebellar), log-transformed initial ICH volume, presence of intraventricular hemorrhage, and surgical interventions. ERICH subjects with a pre-ICH modified Rankin Scale (mRS) score of 3 or lower were included. Treated cases were matched 1:1 to untreated cases by the closest propensity score (difference ≤.15), gender, and race and ethnicity (non-Hispanic white, non-Hispanic black, or Hispanic). The McNemar and the Wilcoxon signed-rank tests were used to compare 3-month mRS outcomes between the 2 groups. Good outcome was defined as a 3-month mRS score of 3 or lower. RESULTS: As of December 31, 2013, the ERICH study enrolled 2279 cases, of which 304 hyperosmolar-treated cases were matched to 304 untreated cases. Treated cases had worse outcome at 3 months compared with untreated cases (McNemar, P = .0326), and the mean 3-month mRS score was lower in the untreated group (Wilcoxon, P = .0174). Post hoc analysis revealed more brain edema, herniation, and death at discharge for treated cases. CONCLUSIONS: Hyperosmolar therapy was not associated with better 3-month mRS outcomes for ICH cases in the ERICH study. This finding likely resulted from greater hyperosmolar therapy use in patients with edema and herniation rather than those agents leading to worse outcomes. Further studies should be performed to determine if hyperosmolar agents are effective in preventing poor outcomes.

Impact of Moderate Hyperchloremia on Clinical Outcomes in Intracerebral Hemorrhage Patients Treated With Continuous Infusion Hypertonic Saline: A Pilot Study.

OBJECTIVES: Hyperchloremia has been associated with increased morbidity and mortality in critically ill patients. While previous research has demonstrated an association between hypertonic saline and hyperchloremia, limited data exist in neurocritical care patients. The objective of this study is to determine the impact of moderate hyperchloremia (chloride ≥ 115 mmol/L) on clinical outcomes in intracerebral hemorrhage patients treated with continuous IV infusion 3% hypertonic saline. DESIGN: Multicenter, retrospective, propensity-matched cohort study. SETTING: Neurocritical care units at two academic medical centers with dedicated neurocritical care teams and comprehensive stroke center designation. PATIENTS: Intracerebral hemorrhage patients discharged between September 2011 and September 2015 were evaluated and matched 1:1 based on propensity scoring. INTERVENTIONS: Continuous IV infusion 3% hypertonic saline. MEASUREMENTS AND MAIN RESULTS: A total of 219 patients were included in the unmatched cohort (143 moderate hyperchloremia and 76 nonhyperchloremia) and 100 patients in the propensity-matched cohort. In-hospital mortality was significantly higher in those who developed moderate hyperchloremia in a propensity-matched cohort (34% vs 14%; p = 0.02). Moderate hyperchloremia independently predicted in-hospital mortality in multivariable logistic regression analysis (odds ratio, 4.4 [95% CI, 1.4-13.5]; p = 0.01). CONCLUSIONS: We observed higher rates of in-hospital mortality in patients who developed moderate hyperchloremia during treatment with continuous IV infusion 3% hypertonic saline, with moderate hyperchloremia independently predicting in-hospital mortality. These results suggest that chloride values should be monitored closely during hypertonic saline treatment as moderate elevations may impact outcomes in intracerebral hemorrhage patients.

Efficacy, Safety, and Timing of 5% Sodium Chloride Compared With 23.4% Sodium Chloride for Osmotic Therapy.

BACKGROUND: Bolus doses of 23.4% sodium chloride (NaCl) are commonly used for the treatment of intracranial hypertension; however, delays in administration may occur in patients without central intravenous access. At our institution, equiosmolar bolus doses of 5% NaCl have emerged as potential alternatives to 23.4% NaCl because they may be safely administered through peripheral lines. OBJECTIVES: We sought to assess the efficacy in reducing intracranial pressure (ICP), time to administration, and safety of 5% NaCl as compared with 23.4% NaCl for the treatment of intracranial hypertension. METHODS: Patients admitted from July 2012 to June 2014 who received boluses of 5% NaCl or 23.4% NaCl for a sustained ICP >20 mm Hg were included. Data collected included measurements of ICP, time to administration, and adverse events. RESULTS: A total of 44 patients were identified; 11 received 5% NaCl, and 33 received 23.4% NaCl. The median percentage reductions in ICP at 30, 60, and 120 minutes in patients who received 5% versus 23.4% NaCl were 34% versus 26% ( P = 0.850), 48% versus 40% ( P = 0.700), and 46% versus 30% ( P = 0.064), respectively. The median time to administration was shorter in the 5% NaCl group (7 vs 11 minutes, P = 0.364). Both groups had a 27% rate of adverse events and no infusion site reactions. CONCLUSIONS: These data suggest that 5% NaCl may be as effective as 23.4% NaCl at lowering ICP if given at equiosmolar doses, has a shorter time to administration, and has no difference in the prevalence of adverse events.

Safety and benefits of inhaled hypertonic saline following airway challenges with endotoxin and allergen in asthmatics.

OBJECTIVE: To determine whether induced sputum (IS) with hypertonic saline inhalation is safe to use in asthmatics within 24 hours of two commonly used airway challenges, namely endotoxin and dust mite allergen, and to assess whether IS can enhance mucociliary clearance (MCC) rates in asthmatics. METHODS: IS (three 7-minute inhalation periods of 3%, 4%, and 5% hypertonic saline) was employed before (N = 29) and within 24 hours of inhaled challenges with endotoxin (N = 13) and dust mite allergen (N = 12) in a cohort of mild to moderate asthmatics. Safety was assessed by lung function (Forced Expiratory Volume in 1 second; FEV1) and MCC was measured using a radiolabeled gamma scintigraphy method (Tcm99 sulfur colloid). IS was performed pre and post MCC. RESULTS: No significant lung function decrement was observed before or after inhaled challenges with endotoxin or dust mite allergen. IS significantly enhanced MCC rates before and after inhaled endotoxin challenge. CONCLUSION: Based on a small cohort, IS is safe to use in mild to moderate asthmatics before and within 24 hours of inhaled challenges with endotoxin and dust mite allergen. Furthermore, IS has beneficial effects on host defense function in asthmatics by enhancing MCC rates.

A Retrospective Study to Evaluate the Effect of Concentration of Hypertonic Saline on Efficacy and Safety of Epidural Adhesiolysis.

BACKGROUND: Percutaneous epidural adhesiolysis (PEA) is a minimally invasive procedure that is performed to relieve low back and/or lower limb pain secondary to adhesions or scarring in the epidural space that is refractory to conservative treatment. The optimal concentration of hypertonic saline might be an important factor in the safety and efficacy of PEA. We evaluated differences in the efficacy and safety of 2 concentrations of hypertonic saline (5% and 10%) used in lumbar PEA at our institutions in a retrospective study. METHODS: Patients who received lumbar PEA between January 2009 and June 2014 at either of 2 large civilian teaching institutions in South Korea were assigned to the 5% or 10% groups according to the osmolality of saline. The primary outcome of this study was the difference in change in the 11-point numerical rating scale (NRS) scores of low back and leg pain from baseline to 6 months after PEA between patients in the 2 groups. The number of additional epidural injections, patients' satisfaction with PEA, and any complications that occurred within 6 months after PEA were reviewed. RESULTS: This study included 543 patients (5% group, 333; 10% group, 210). Post-PEA NRS pain scores were significantly lower compared with those at baseline in both groups; however, there were no significant differences between the 2 groups at 6 months or any time point after PEA with regard to any of the clinical characteristics, except infusion-related pain, which exhibited borderline significance for greater scores in the 10% group compared with those in the 5% group (P = .041). Multivariable linear regression analysis with adjustments for covariates, including the number of additional epidural injections, revealed no significant association between patient group and the decrease in NRS pain scores at 6 months of follow-up. Transient adverse events related to PEA were recorded in 3 patients (10% group, 2; 5% group, 1). CONCLUSIONS: In PEA, 5% hypertonic saline exhibited similar positive outcomes after 6 months of follow-up as 10% hypertonic saline, with less infusion-related pain. This result suggests that infusion of 5% hypertonic saline may be considered as an alternative to 10% hypertonic saline in lumbar PEA. Further prospective randomized studies are required to better appreciate the outcome with regard to the use of different concentrations of hypertonic saline for PEA.