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1.
The challenges of sodium measurements: indirect versus direct ion-selective method.
Refardt, J, Sailer, CO, Chifu, I, Winzeler, B, Schnyder, I, Fassnacht, M, Fenske, W, Christ-Crain, M
European journal of endocrinology. 2019;(2):193-199
Abstract
BACKGROUND Diagnosis and treatment of dysnatremia is challenging and further complicated by the pitfalls of different sodium measurement methods. Routinely used sodium measurements are the indirect (plasma/serum) and direct (whole blood) ion-selective electrode (ISE) method, showing discrepant results especially in the setting of acute illness. Few clinicians are aware of the differences between the methods in clinically stable patients or healthy volunteers. METHODS Data of 140 patients and 91 healthy volunteers undergoing osmotic stimulation with hypertonic saline infusion were analyzed. Sodium levels were measured simultaneously by indirect and direct ISE method before and at different time points during osmotic stimulation up to a sodium threshold of ≥150 mmol/L. The primary outcome was the difference in sodium levels between the indirect and direct ISE method. RESULTS 878 sodium measurements were analyzed. Mean (s.d.) sodium levels ranged from 141 mmol/L (2.9) to 151 mmol/L (2.1) by the indirect ISE compared to 140 mmol/L (3) to 149 mmol/L (2.8) by the direct ISE method. The interclass correlation coefficient between the two methods was 0.844 (95% CI: 0.823-0.863). On average, measurements by the indirect ISE were 1.9 mmol/L (95% CI limits: -3.2 to 6.9) higher than those by the direct ISE method (P < 0.001). The tendency of the indirect ISE method resulting in higher levels increased with increasing sodium levels. CONCLUSION Intra-individual sodium levels differ significantly between the indirect and direct ISE method also in the absence of acute illness. It is therefore crucial to adhere to the same method in critical situations to avoid false decisions due to measurement differences.
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2.
Release and Decay Kinetics of Copeptin vs AVP in Response to Osmotic Alterations in Healthy Volunteers.
Fenske, WK, Schnyder, I, Koch, G, Walti, C, Pfister, M, Kopp, P, Fassnacht, M, Strauss, K, Christ-Crain, M
The Journal of clinical endocrinology and metabolism. 2018;(2):505-513
Abstract
CONTEXT Copeptin is the C-terminal fragment of the arginine vasopressin (AVP) prohormone whose measurement is more robust than that of AVP. Similar release and clearance characteristics have been suggested promoting copeptin as a surrogate marker. OBJECTIVE To characterize the physiology of osmotically regulated copeptin release and its half-life in direct comparison with plasma AVP. DESIGN Ninety-one healthy volunteers underwent a standardized three-phase test protocol including (1) osmotic stimulation into the hypertonic range by hypertonic-saline infusion followed by osmotic suppression via (2) oral water load and (3) subsequent glucose infusion. Plasma copeptin, AVP, serum sodium, and osmolality levels were measured in regular intervals. RESULTS In phase 1, an increase in median osmotic pressure [289 (286; 291) to 311 (309; 314) mOsm/kg H2O] caused similar release kinetics of plasma copeptin [4 (3.1; 6) to 29.3 (18.6; 48.2) pmol/L] and AVP [1 (0.7; 1.6) to 10.3 (6.8; 18.8) pg/mL]. Subsequent osmotic suppression to 298 (295; 301) mOsm/kg at the end of phase 3 revealed markedly different decay kinetics between both peptides-an estimated initial half-life of copeptin being approximately 2 times longer than that of AVP (26 vs 12 minutes). CONCLUSION Copeptin is released in equimolar amounts with AVP in response to osmotic stimulation, suggesting its high potential as an AVP surrogate for differentiation of osmotic disorders. Furthermore, we here describe the decay kinetics of copeptin in response to osmotic depression enabling to identify a half-life for copeptin in direct comparison with AVP.
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3.
Abnormal urinary excretion of NKCC2 and AQP2 in response to hypertonic saline in chronic kidney disease: an intervention study in patients with chronic kidney disease and healthy controls.
Jensen, JM, Mose, FH, Kulik, AE, Bech, JN, Fenton, RA, Pedersen, EB
BMC nephrology. 2014;:101
Abstract
BACKGROUND Renal handling of sodium and water is abnormal in chronic kidney disease (CKD). The aim of this study was to test the hypothesis that abnormal activity of the aquaporin-2 water channels (AQP2), the sodium-potassium-2chloride transporter (NKCC2) and/or the epithelial sodium channels (ENaC) contribute to this phenomenon. METHODS 23 patients with CKD and 24 healthy controls at baseline and after 3% saline infusion were compared. The following measurements were performed: urinary concentrations of AQP2 (u-AQP2), NKCC2 (u-NKCC2), ENaC (u-ENaCγ), glomerular filtration rate (GFR) estimated by 51Cr-EDTA clearance, free water clearance (CH2O), urinary output (UO), fractional excretion of sodium (FENa), plasma concentrations of AVP, renin (PRC), Angiotensin II (ANG II), Aldosterone (Aldo) and body fluid volumes. RESULTS At baseline, GFR was 34 ml/min in CKD patients and 89 ml/ml in controls. There were no significant differences in u-AQP2, u-NKCC2 or u-ENaCγ, but FENa, p-Aldo and p-AVP were higher in CKD patients than controls. In response to hypertonic saline, patients with CKD had an attenuated decrease in CH2O and UO. A greater increase in U-AQP2 was observed in CKD patients compared to controls. Furthermore, u-NKCC2 increased in CKD patients, whereas u-NKCC2 decreased in controls. Body fluid volumes did not significantly differ. CONCLUSIONS In response to hypertonic saline, u-NKCC2 increased, suggesting an increased sodium reabsorption via NKCC2 in patients with CKD. U-AQP2 increased more in CKD patients, despite an attenuated decrease in CH2O. Thus, though high levels of p-AVP and p-Aldo, the kidneys can only partly compensate and counteract acute volume expansion due to a defective tubular response. TRIAL REGISTRATION Clinical trial no: NCT01623661. Date of trial registration: 18.06.2012.
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4.
Dural sac cross-sectional area does not correlate with efficacy of percutaneous adhesiolysis in single level lumbar spinal stenosis.
Park, CH, Lee, SH, Jung, JY
Pain physician. 2011;(4):377-82
Abstract
BACKGROUND Spinal stenosis is a narrowing of the spinal canal, which causes mechanical compression of spinal nerve roots. The compression of these nerve roots can cause low back pain and/or leg pain, as well as neurogenic claudication. Lumbar epidural steroid injections have commonly been used in patients with lumbar spinal stenosis (LSS). In cases that are refractory to epidural steroid injections, percutaneous epidural adhesiolysis has been used. OBJECTIVE The aim of our study is to determine the relationship between the severity of spinal stenosis and the participants' response to adhesiolysis, and to evaluate the mid-term effectiveness of adhesiolysis. STUDY DESIGN A prospective observational study. METHODS Sixty-six patients with degenerative LSS were enrolled in this prospective study. All participants underwent lumbar spine magnetic resonance imaging (MRI). The cross-sectional area of the dural sac was measured on the transverse angled sections through the central part of the disc on conventional MR images. All percutaneous adhesiolyses were performed in the operating room. One hour following the procedure, 6 mL of 8% sodium chloride solution was infused during 30 minutes in the recovery room while the patient underwent monitoring. Outcome measures were obtained using the 5-point patient satisfaction scale at 2 weeks and 6 months post-treatment. To evaluate outcome predictors, we divided the participants into 2 groups according to their response to treatment. LIMITATIONS Secondary outcomes were not measured and the study did not include a long-term follow-up period. RESULTS Improvement (including reports of slightly improved, much improved, and no pain) was observed in 49 participants (74.2%) at 2 weeks and 45 participants (66.7%) at 6 months after the procedure. The dural sac cross-sectional area (DSCSA) did not differ between participants who reported improvement and those who did not. There was no statistically significant correlation between pain relief and DSCSA, age, or participant sex. CONCLUSION Percutaneous adhesiolysis was shown to be effective for the treatment of LSS, with mid-term result, without affecting DSCSA.
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5.
Hypertonic saline inhibits luminal sodium channels in respiratory epithelium.
Hebestreit, A, Kersting, U, Hebestreit, H
European journal of applied physiology. 2007;(2):177-83
Abstract
Physical exercise with increased ventilation leads to a considerable rise in water loss from the airways. The mechanisms underlying the regulation of transepithelial fluid transport necessary to compensate for these losses are unknown but may include changes in luminal ion channel conductance. The present study was designed to examine the effects of an increase in luminal chloride and sodium concentrations which may locally occur during hyperventilation on luminal ion conductance in the respiratory epithelium of healthy controls and patients diagnosed with cystic fibrosis (CF). Changes in luminal chloride and sodium conductance were inferred by recording nasal potential difference in eight healthy subjects and 10 patients with CF, using superfusing solutions based on isotonic saline (150 mM) on one occasion and solutions based on hypertonic saline (300 mM) on the other. Switching from isotonic to hypertonic saline superfusion decreased potential difference in controls and CF patients significantly. Amiloride induced a decrease of potential difference which was larger with isotonic than with hypertonic saline (controls 9.5 +/- 6.1 vs. 3.7 +/- 4.6 mV; CF 17.2 +/- 7.2 vs. 9.8 +/- 7.6 mV). Chloride conductance stimulated with solutions low in chloride and containing isoproterenol was not significantly changed by hypertonic saline solutions compared with isotonic solutions in both groups. The findings indicate a significant inhibition of luminal sodium conductance by high luminal sodium concentrations. This mechanism may be involved in the regulation of fluid transport across the respiratory epithelium during exercise and in the improvement of mucociliary clearance and lung functions with inhalation of hypertonic saline in CF.
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6.
Changes in brain natriuretic peptide levels and bioelectrical impedance measurements after treatment with high-dose furosemide and hypertonic saline solution versus high-dose furosemide alone in refractory congestive heart failure: a double-blind study.
Paterna, S, Di Pasquale, P, Parrinello, G, Fornaciari, E, Di Gaudio, F, Fasullo, S, Giammanco, M, Sarullo, FM, Licata, G
Journal of the American College of Cardiology. 2005;(12):1997-2003
Abstract
OBJECTIVES The aim of this study was to evaluate the effect of a new treatment for refractory congestive heart failure (CHF) on brain natriuretic peptide (BNP) plasma levels and hydration station. BACKGROUND The study was aimed at evaluating the effects of the combination of high-dose furosemide and small-volume hypertonic saline solution (HSS) in refractory CHF patients. METHODS A total of 94 patients (34 women/60 men) with refractory CHF (age 55 to 80 years) were enrolled. They had to have an ejection fraction <35%, serum creatinine <2 mg/dl, blood urea nitrogen <60 mg/dl, a reduced urinary volume, and a low natriuresis (<500 ml/24 h and <60 mEq/24 h, respectively). Patients were divided (double-blind) into two groups: group 1 (18 women/30 men) received an intravenous furosemide (500 to 1,000 mg) plus HSS twice a day in 30 min. Group 2 (16 women/30 men) received an intravenous bolus of furosemide (500 to 1,000 mg/twice a day) alone, for four to six days. At entry, body weight, blood pressure, heart rate, and laboratory parameters were checked during hospitalization; BNP levels were measured on admission, 6 and 30 days after discharge, while on admission and 6 days after, impedance plethysmography was performed. The HSS group received 120 mmol of Na intake versus 80 mmol in non-HSS group. Fluid intake of 1,000 was given to both groups. RESULTS The groups were similar for clinical characteristics. A significant increase in daily diuresis and natriuresis was observed in HSS group, p < 0.05. The BNP values showed significant intragroup and intergroup differences, 6 and 30 days after treatment. The patients from the HSS group reached a better hydration state than the non-HSS group after six days. In addition, the HSS group showed a significant reduction in hospitalization time and readmission rate. CONCLUSIONS Our data show that the HSS group reached dry weight more rapidly, a significantly faster reduction in BNP levels, shorter hospitalization stay, and lower incidence in readmissions in the 30-day study period.
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7.
Prehospital hypertonic saline resuscitation of patients with hypotension and severe traumatic brain injury: a randomized controlled trial.
Cooper, DJ, Myles, PS, McDermott, FT, Murray, LJ, Laidlaw, J, Cooper, G, Tremayne, AB, Bernard, SS, Ponsford, J, ,
JAMA. 2004;(11):1350-7
Abstract
CONTEXT Prehospital hypertonic saline (HTS) resuscitation of patients with traumatic brain injury (TBI) may increase survival but whether HTS improves neurological outcomes is unknown. OBJECTIVE To determine whether prehospital resuscitation with intravenous HTS improves long-term neurological outcome in patients with severe TBI compared with resuscitation with conventional fluids. DESIGN, SETTING, AND PATIENTS Double-blind, randomized controlled trial of 229 patients with TBI who were comatose (Glasgow Coma Scale score, <9) and hypotensive (systolic blood pressure, <100 mm Hg). The patients were enrolled between December 14, 1998, and April 9, 2002, in Melbourne, Australia. INTERVENTIONS Patients were randomly assigned to receive a rapid intravenous infusion of either 250 mL of 7.5% saline (n = 114) or 250 mL of Ringer's lactate solution (n = 115; controls) in addition to conventional intravenous fluid and resuscitation protocols administered by paramedics. Treatment allocation was concealed. MAIN OUTCOME MEASURE Neurological function at 6 months, measured by the extended Glasgow Outcome Score (GOSE). RESULTS Primary outcomes were obtained in 226 (99%) of 229 patients enrolled. Baseline characteristics of the groups were equivalent. At hospital admission, the mean serum sodium level was 149 mEq/L for HTS patients vs 141 mEq/L for controls (P<.001). The proportion of patients surviving to hospital discharge was similar in both groups (n = 63 [55%] for HTS group and n = 57 [50%] for controls; P =.32); at 6 months, survival rates were n = 62 (55%) in the HTS group and n = 53 (47%) in the control group (P =.23). At 6 months, the median (interquartile range) GOSE was 5 (3-6) in the HTS group vs 5 (5-6) in the control group (P =.45). There was no significant difference between the groups in favorable outcomes (moderate disability and good outcome survivors [GOSE of 5-8]) (risk ratio, 0.99; 95% confidence interval, 0.76-1.30; P =.96) or in any other measure of postinjury neurological function. CONCLUSION In this study, patients with hypotension and severe TBI who received prehospital resuscitation with HTS had almost identical neurological function 6 months after injury as patients who received conventional fluid.
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8.
Effects of buffered saline solution on nasal mucociliary clearance and nasal airway patency.
Keojampa, BK, Nguyen, MH, Ryan, MW
Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery. 2004;(5):679-82
Abstract
OBJECTIVE To compare the effects of buffered hypertonic and buffered normal saline nasal spray on mucociliary clearance and nasal airway patency. STUDY DESIGN AND SETTING Double-blind trial with subjects acting as their own controls. Tertiary care academic medical center. RESULTS Buffered hypertonic saline and buffered normal saline both improved saccharine clearance times ( P < 0.0001 for buffered hypertonic and P = 0.002 for buffered normal saline). Buffered hypertonic saline improved saccharine clearance times more than buffered normal saline (39.6% vs 24.1%, P = 0.007). Neither buffered hypertonic nor buffered normal saline significantly affected nasal airway patency. CONCLUSIONS Both buffered hypertonic and buffered normal saline nasal spray significantly improved saccharine clearance times without affecting nasal airway patency. Buffered hypertonic saline affected saccharine clearance times to a greater degree than buffered normal saline. CLINICAL SIGNIFICANCE Buffered hypertonic and buffered normal saline sprays both improve mucociliary clearance and should therefore be beneficial in conditions such as rhinitis and sinusitis, which are associated with disruption of mucociliary clearance. However, these sprays do not appear to affect the nasal airway. Patients may therefore benefit from other treatments for "nasal congestion." EBM RATING B-2.
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9.
[Short term effects of hypertonic saline during severe sepsis and septic shock].
Muller, L, Lefrant, JY, Jaber, S, Louart, G, Mahamat, A, Ripart, J, de La Coussaye, JE, Eledjam, JJ
Annales francaises d'anesthesie et de reanimation. 2004;(6):575-80
Abstract
OBJECTIVE Assessment of haemodynamic effects of 250 ml hypertonic saline 7.5% (HS) perfusion in critically ill patients with severe sepsis or septic shock. STUDY DESIGN Observational study. PATIENTS Twelve mechanically ventilated patients with severe sepsis or septic shock requiring a pulmonary artery catheter and volume loading. INTERVENTION Two hundred and fifty millilitres HS were given over 15 min. Were measured: heart rate (HR), mean arterial pressure (MAP) and pulmonary artery pressure (MPAP), pulmonary capillary wedge pressure (PCWP), right atrial pressure (RAP), cardiac index (CI), indexed systemic vascular resistance (ISVR), indexed pulmonary vascular resistance (IPVR), plasma sodium, chloride, protein and haemoglobin concentrations and arterial blood lactate. Studied parameters were assessed at baseline (T(0)) and 5 (T(0)) and 105 min (T(120)) after the end of HS infusion. RESULTS MAP, HR and RAP were not altered. HS increased PAPM (25 +/- 5-30 +/- 6 mmHg), PCWP (13 +/- 3-18 +/- 4 mmHg) and CI (3.5 +/- 1.2-4.6 +/- 1.1 l/min per m(2)) at T(20) (P < 0.05). ISVR and IPVR were decreased at T(20). Protein and haemoglobin were decreased at T(20). Sodium and chloride were increased at T(20) (from 136 +/- 4 to 147 +/- 4 and from 110 +/- 6 to 123 +/- 6 mmol/l, respectively, P < 0.01) and T(120). CONCLUSION In patients with severe sepsis or septic shock, 250 ml HS transiently (<120 min) increases CI and PCWP and induces an increase in sodium and chloride concentrations.
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10.
[Effects of equiosmolar load of 20% mannitol, 7.5% saline and 0.9% saline on plasma osmolarity, haemodynamics and plasma concentrations of electrolytes].
Erard, AC, Walder, B, Ravussin, P
Annales francaises d'anesthesie et de reanimation. 2003;(1):18-24
Abstract
OBJECTIVES Mannitol 20% (M) and NaCl 7.5% (H) are hypertonic solutions used in-patient in hypovolaemic shock and in case of increased ICP. To our knowledge no study in humans compared them in an equiosmolar load. The objectives of this study were to compare the pharmacokinetics of both solutions in an equiosmolar load with an isotonic solution (NaCl 0.9% (C)) in terms of osmolarity, electrolytes and haemodynamic parameters over time. STUDY DESIGN Prospective, randomized, controlled study. PATIENTS Thirty ASA I and II patients undergoing non haemorrhagic surgery under general anesthesia. METHODS Three groups were studied (groups M, H and C), each receiving an equiosmolar load (4.95 mOsm kg(-1)) of solutions of mannitol 20%, saline 7.5% and saline 0.9% over ten minutes. Vital parameters (non invasive blood pressure, heart rate, oesophageal temperature) were monitored and blood samples (hemoglobin, hematocrit, K(+), Na(+), Cl(-), urea, creatinine, glucose, mannitolemia, osmolarity) were assessed preoperatively and intraoperatively at times 0, 3, 5, 10, 15, 30, 45, 60, 90, 120, 150 min of perfusion. RESULTS In both hypertonic groups, osmolarity was maximal at the end of infusion (group M: 329 +/- 7 mOsm l(-1); group H: 321 +/- 11 mOsm l(-1)); at the same time, Na(+) value was lowest in group M: 129 +/- 3 mmol l(-1) and highest in group H: 151 +/- 5 mmol l(-1), P < 0.001) with normalisation at 60 min. These results were also statistically significant when compared to the isotonic group (group C: osmolarity: 296 +/- 3 mOsm l(-1), P < 0.001; Na(+): 140 +/- 2 mmol l(-1), P < 0.001). Plasma volume expansion was statistically significantly larger in-group C between 10 and 15 min compared to both hypertonic groups (haematocrit: group C: 35 +/- 4%, group M: 39 +/- 5%; group H: 41 +/- 3%, P < 0.004). Haemodynamic parameters were similar in the 3 groups with however a trend towards lowers HR in the mannitol group, particularly at T10. Temperature was lower in the control group because of the volume infused. Cl(-) was higher in the H group. CONCLUSION A single infusion of 4.95 mOsm kg(-1) of mannitol 20% or NaCl 7.5% induces a similar osmolar variation over time with a maximal effect after 10 min.