Small Volume Hypertonic Saline Research Articles

The safety and efficacy of fluid resuscitation with hypertonic saline in traumatic hypovolemic shock: a meta-analysis

Objective To assess the safety and efficacy of hypertonic saline in traumatic hypovolemic shock with Meta-analysis. Methods Comprehensive electronic search strategies were developed using the following electronic databases: PubMed, EMBASE, Medline, Ovid、Clinical Trials, CNKI, Wan Fang, CBM and FMJS. The Literature published before August of 2017 was searched. The randomized controlled trials (RCTs) about hypertonic saline in traumatic hypovolemic shock were included. A data-extraction sheet was developed based on the preset standards. The data from eligible studies were pooled through Meta-analysis. Results 9 trials with a total of 1600 patients(741cases in observation group, 859 cases in control group ) met the inclusion criteria. The meta-analysis showed that the hypertonic saline group displayed remarkable increase in the systolic blood pressure and decrease in hemoglobin level, compared with the isotonic saline group [MD=6.43, 95% CI(1.16, 11.70), P 0.05]. Conclusions Available evidence shows that small volume hypertonic Sodium Chloride saline is safe and effective for resuscitation in patients with traumatic hemorrhagic shock. Since the quality of the inclued studes were not high, more high-quality, multicenter randomized controlled clinical studies need to provide better evidence for the above conclusion. Key words: Saline solution, hypertonic/TU; Shock, traumatic/DT; Resuscitation/MT; Meta-analysis

Hypertonic saline with furosemide for diuretic resistant congestive heart failure in an infant

Hypertonic saline with intravenous furosemide therapy for diuretic resistant congestive heart failure has been postulated in adults [ 1 Liszkowski M. Nohria A. Rubbing salt into wounds: hypertonic saline to assist with volume removal in heart failure. Curr. Heart Fail. Rep. 2010; 7: 134-139 Crossref PubMed Scopus (17) Google Scholar , 2 Vecchis R.D. Esposito C. Ariano C. Cantatrione S. Hypertonic saline plus i.v. furosemide improve renal safety profile and clinical outcomes in acute decompensated heart failure. Herz. 2015; 40: 423-435 Crossref PubMed Scopus (30) Google Scholar , 3 Paterna S. Di Pasquale P. Parrinello G. Amato P. Cardinale A. Follone G. Giubilato A. Licata G. Effects of high-dose furosemide and small-volume hypertonic saline solution infusion in comparison with a high dose of furosemide as a bolus, in refractory congestive heart failure. Eur. J. Heart Fail. 2000; 2: 305-313 Crossref PubMed Scopus (96) Google Scholar ]. Low-volume hypertonic saline administration transiently improves hemodynamics, enhances natriuresis and preserves renal function [ [1] Liszkowski M. Nohria A. Rubbing salt into wounds: hypertonic saline to assist with volume removal in heart failure. Curr. Heart Fail. Rep. 2010; 7: 134-139 Crossref PubMed Scopus (17) Google Scholar ]. However, concerning congestive heart failure in children, there is little evidence about the efficacy of hypertonic saline therapy. This report presents an infant who recovered from severe congestive heart failure by hypertonic saline therapy.

Effects of Small-Volume Hypertonic Saline on Acid-Base and Electrolytes Balance in Rats With Peritonitis-Induced Sepsis

Our previous study has demonstrated that hypertonic saline (HS) given at 3 h after cecal ligation and puncture (CLP) surgery alleviates circulatory failure, multiple organ dysfunction syndrome, and mortality rate in rats. However, only few data exist on the application of HS in acid-base and electrolyte imbalance of sepsis. In addition, early one-dose HS administration seems to have only modest improvement on mortality rate. Thus, we evaluated the effects of HS on acid-base equilibrium and electrolyte balance in CLP-induced sepsis model and further compared with the effects of two- and one-dose HS administration. Male Wistar rats received CLP or sham operation followed by the administration of saline or HS (7.5% NaCl, 4 mL/kg, intravenously at 3 and 9 h after laparotomy or CLP). The changes in hemodynamics, biochemical variables, blood gas, electrolytes, organ histology, and plasma levels of nitric oxide (NO) and interleukin 1β (IL-1β) were examined during the 18-h observation. Hypertonic saline given either at 3 h (one-dose administration) or at 3 and 9 h (two-dose administration) after CLP attenuated circulatory failure, multiple organ dysfunction syndrome, metabolic acidosis, hyperkalemia, neutrophil infiltration, and 18-h mortality. Moreover, both one- and two-dose HS administrations significantly diminished plasma NO and IL-1β levels in CLP rats. However, only the two-dose HS administration significantly improved hyponatremia and hypocalcemia in septic rats. Beneficial effects of HS in septic rats may be attributed to not only reducing plasma levels of NO and IL-1β, but also improving metabolic acidosis and electrolyte imbalance. In addition, two-dose HS administration could reverse electrolyte imbalance caused by CLP.

Comparison of hypertonic saline versus normal saline on cytokine profile during CABG

Background and the purpose of the studyBlood contact with artificial surfaces of the extracorporeal circuit and ischemia-reperfusion injury in CABG with CPB, may lead to a systemic inflammatory response. Hypertonic saline have been recently investigated as a fluid in order to decrease inflammatory response and cytokines generation in patients undergo cardiac operations. Our purpose is to study the prophylactic effect of HS 5% infusion versus NS on serum IL-6 as an inflammatory & IL-10 as an anti-inflammatory biomarker in CABG patients.MethodsThe present study is a randomized double-blinded clinical trial. 40 patients undergoing CABG were randomized to receive HS 5% or NS before operation. Blood samples were obtained after receiving HS or NS, just before operation, 24 and 48 hours post-operatively. Plasma levels of IL-6 and IL-10 were measured by ELISA.Results and major conclusionPatients received HS had lower levels of IL-6 and higher level of IL-10 compared with NS group, however these differences were not statistically significant. Results of this study suggest that pre-treatment with small volume hypertonic saline 5% may have beneficial effects on inflammatory response following CABG operation.

Chapter 8. Hyperosmolar therapy

Chapter 8. Hyperosmolar therapy

The progress of perioperative fluid therapy Strategy

Background Adopting appropriate fluid therapy strategy for perioperative patients is essential to perioperative management, which could reduce perioperative complications, shorten hospitalization days and prognosis of postoperative patients. Objective In order to provide evidence for clinical selection of fluid therapy strategy, we reviewed the history and the progress of perioperative fluid therapy strategy and generate current best evidence of some controversial issues. Content We reviewed the history and the progress of perioperative fluid therapy strategy, including early goal directed therapy, the strategy of fast track surgery, acute high-capacity perfusion during anesthesia induction and small volume hypertonic saline resuscitation. We also summarized some controversial issues such as the selection of fluid for resuscitation and the security of artificial colloid. Trend To achieve the fundamental goal of improve the organ perfusion and oxygen delivery to protect organ function, future study are warranted to the technology and approach of fluid assessment and monitoring. It is urgent to explore new resuscitation fluid which has reliable effect with mild adverse reactions. Key words: Perioperative period; Fluid therapy; Crystal; Colloid

Small Volume 7.5% NaCl With 6% Dextran-70 or 6% and 10% Hetastarch Are Associated With Arrhythmias and Death After 60 Minutes of Severe Hemorrhagic Shock in the Rat In Vivo

Hypertonic saline solutions in combination with colloids may have some applications in critically ill patients. Our aim was to examine the effects of small volumes (0.7-1 mL/kg intravenous) of 7.5% NaCl with different colloids on cardiac stability, hemodynamics, and mortality after severe hemorrhagic shock. Male fed Sprague-Dawley rats (300-450 g, n = 48) were anesthetized and randomly assigned to one of six groups: (1) untreated (bleed only), (2) 7.5% NaCl, (3) 7.5% NaCl/6% dextran-70, (4) 7.5% NaCl/6% hetastarch (HES), (5) 6% HES alone, and (6) 7.5% NaCl/10% HES. Hemorrhagic shock was induced by phlebotomy until the mean arterial pressure (MAP) was 35 mm Hg to 40 mm Hg and continued for 20 minutes until ∼40% blood loss. Animals were left in shock for 60 minutes at 34°C. 0.3 mL (<4% of shed blood) was injected as a 10 seconds bolus into the femoral vein. Lead II electrocardiogram, blood pressures, MAP, and heart rate were monitored. Untreated rats were highly arrhythmogenic with 38% mortality. 7.5% NaCl increased MAP from 39 mm Hg to 44 mm Hg with no severe arrhythmias or mortality. Dextran-70 increased MAP from 38 mm Hg to 49 mm Hg, transiently increased QRS amplitude (1.5 times) and was arrhythmogenic affecting 50% of animals with no deaths. Addition of 6% HES to hypertonic saline resulted in aberrant arrhythmias and 38% mortality. Six percent HES alone was proarrhythmic and led to 38% mortality. 7.5% NaCl with 10% HES resulted in 100% mortality (p < 0.05) from arrhythmias within 5 minutes of resuscitation. Small volumes of 7.5% NaCl led to fewer arrhythmias and a 2.6 times survival benefit over untreated rats, and a partial resuscitation of MAP into the "permissive range." Dextran-70 or HES in 7.5% NaCl were proarrhythmic and HES led to increased mortality (p < 0.05). Because optimal heart function is critical for successful resuscitation, care should be exercised when using dextran-70 or 6 and 10% HES in small volume hypertonic saline solutions for early hypotensive resuscitation.

Hypertonic sodium resuscitation after hemorrhage improves hemodynamic function by stimulating cardiac, but not renal, sympathetic nerve activity

Small volume hypertonic saline resuscitation can be beneficial for treating hemorrhagic shock, but the mechanism remains poorly defined. We investigated the effects of hemorrhagic resuscitation with hypertonic saline on cardiac (CSNA) and renal sympathetic nerve activity (RSNA) and the resulting cardiovascular consequences. Studies were performed on conscious sheep instrumented with cardiac (n=7) and renal (n=6) sympathetic nerve recording electrodes and a pulmonary artery flow probe. Hemorrhage (20 ml/kg over 20 min) caused hypotension and tachycardia followed by bradycardia, reduced cardiac output, and abolition of CSNA and RSNA. Resuscitation with intravenous hypertonic saline (1.2 mol/l at 2 ml/kg) caused rapid, dramatic increases in mean arterial pressure, heart rate, and CSNA, but had no effect on RSNA. In contrast, isotonic saline resuscitation (12 ml/kg) had a much delayed and smaller effect on CSNA, less effect on mean arterial pressure, no effect on heart rate, but stimulated RSNA, although the plasma volume expansion was similar. Intracarotid infusion of hypertonic saline (1 ml/min bilaterally, n=5) caused similar changes to intravenous administration, indicating a cerebral component to the effects of hypertonic saline. In further experiments, contractility (maximum change in pressure over time), heart rate, and cardiac output increased significantly more with intravenous hypertonic saline (2 ml/kg) than with Gelofusine (6 ml/kg) after hemorrhage; the effects of hypertonic saline were attenuated by the β-receptor antagonist propranolol (n=6). These results demonstrate a novel neural mechanism for the effects of hypertonic saline resuscitation, comprising cerebral stimulation of CSNA by sodium chloride to improve cardiac output by increasing cardiac contractility and rate and inhibition of RSNA.

Fluid Resuscitation With Isotonic or Hypertonic Saline Solution Avoids Intraneural Calcium Influx After Traumatic Brain Injury Associated With Hemorrhagic Shock

Calcium is one of the triggers involved in ischemic neuronal death. Because hypotension is a strong predictor of outcome in traumatic brain injury (TBI), we tested the hypothesis that early fluid resuscitation blunts calcium influx in hemorrhagic shock associated to TBI. Fifteen ketamine-halothane anesthetized mongrel dogs (18.7 kg +/- 1.4 kg) underwent unilateral cryogenic brain injury. Blood was shed in 5 minutes to a target mean arterial pressure of 40 mm Hg to 45 mm Hg and maintained at these levels for 20 minutes (shed blood volume = 26 mL/kg +/- 7 mL/kg). Animals were then randomized into three groups: CT (controls, no fluid resuscitation), HS (7.5% NaCl, 4 mL/kg, in 5 minutes), and LR (lactate Ringer's, 33 mL/kg, in 15 minutes). Twenty minutes later, a craniotomy was performed and cerebral biopsies were obtained next to the lesion ("clinical penumbra") and from the corresponding contralateral side ("lesion's mirror") to determine intracellular calcium by fluorescence signals of Fura-2-loaded cells. Controls remained hypotensive and in a low-flow state, whereas fluid resuscitation improved hemodynamic profile. There was a significant increase in intracellular calcium in the injured hemisphere in CT (1035 nM +/- 782 nM), compared with both HS (457 nM +/- 149 nM, p = 0.028) and LR (392 nM +/- 178 nM, p = 0.017), with no differences between HS and LR (p = 0.38). Intracellular calcium at the contralateral, uninjured hemisphere was 438 nM +/- 192 nM in CT, 510 nM +/- 196 nM in HS, and 311 nM +/- 51 nM in LR, with no significant differences between them. Both small volume hypertonic saline and large volume lactated Ringer's blunts calcium influx in early stages of TBI associated to hemorrhagic shock. No fluid resuscitation strategy promotes calcium influx and further neural damage.

Changes in natriuretic peptide and cytokine plasma levels in patients with heart failure, after treatment with high dose of furosemide plus hypertonic saline solution (HSS) and after a saline loading

Background and Aims Neurohormonal activation and inflammation characterizes heart failure, relates to outcome, and is a therapeutic target. The aim of this study was to evaluate the effects of high-dose furosemide plus small-volume hypertonic saline solutions (HSS) on natriuretic peptides and immuno-inflammatory marker levels and to analyze, after treatment, the response to acute saline loading. Methods and Results 120 patients with heart failure treated with high-dose furosemide + HSS ( Furosemide/HSS group) were matched with: 30 subjects with heart failure treated with high-dose furosemide ( furosemide group), 30 controls with asymptomatic left-ventricular dysfunction (ALVD) ( asymptomatic group) and 30 controls without heart failure or ALVD ( Healthy group). We evaluated plasma levels of natriuretic peptides and cytokine levels in baseline, after treatment and after acute saline load. After treatment with high-dose furosemide + HSS compared to treatment with furosemide alone we observed a significant lowering of ANP [96 (46.5–159.5) pg/ml vs 64 (21–150) pg/ml], BNP [215.5 (80.5–487) pg/ml vs 87 (66–141.5) pg/ml], TNF-α [389.5 (265–615.5) pg/ml vs 231.5 (156–373.5) pg/ml], IL-1β [8 (7–9) pg/ml vs 4 (3–7) pg/ml], IL-6 [5 (3–7.5) pg/ml vs 3 (2–4) pg/ml], plasma values and after an acute saline load, a lower percentage change of ANP (+18.6% vs +28.03% vs +25% vs +29%), BNP (+14.5% vs +29.2% vs +30% vs +29.6%) TNF-α (+10.8% vs +15.8% vs +17.8% vs +11.3%), IL-1β (+20% vs 34.4% vs 40% vs 34.4%) compared to control groups. Conclusions Treatment with HSS could be responsible for a stretching relief that could influence natriuretic and immuno-inflammatory markers.

PC-FACS

PC-FACS

High-Dose Furosemide and Small-Volume Hypertonic Saline Solution Infusion for the Treatment of Leg Edema in Advanced Cancer Patients

Peripheral edema is a common feature in populations with advanced cancer, although it is seldom recognized. Diuretics are commonly employed and may show some benefit, but there are insufficient clinical trial data to draw useful conclusions about their clinical use. The aim of this prospective study was to evaluate the efficacy and tolerability of high-dose furosemide and small-volume hypertonic saline solution infusion in reducing leg edema in patients with advanced cancer treated unsuccessfully with diuretics. A prospective study was performed in a consecutive sample of 24 patients admitted to a pain relief and palliative care unit over a period of 18 months. To be eligible to enter the trial, advanced cancer patients had to have diffuse bilateral leg edema unresponsive to common doses of diuretics. A solution of 60 mEq of NaCl, 250 mg of furosemide, and 150 mL of normal saline were infused over 20 minutes. The treatment was repeated twice a day for two days and eventually continued on the basis of the clinical outcome. Circumferences were measured at the foot, ankle, calf, and thigh before starting the treatment ( T 0) and at intervals of 24 hours ( T 1 and so on). At the same intervals, diuresis was determined. Patients were asked to score their sensation of leg weakness/heaviness on a numerical scale from 0 to 10, before ( T 0) and after the treatment ( T end). An appreciable improvement in the sensation of weakness/heaviness (score reduction of at least two points) was recorded in all the patients. A small decrease in leg circumferences at the different sites was found, and a mean of 3600 mL/day of diuresis was recorded. These observations suggest that high-dose furosemide and small-volume saline may be an effective strategy for the treatment of peripheral edema in patients with advanced cancer.

NON-INVASIVE DETECTION OF PCWP IN DECOMPENSATED HEART FAILURE PATIENTS TREATED WITH INTRAVENOUS HIGH-DOSE FUROSEMIDE AND SMALL-VOLUME HYPERTONIC SALINE SOLUTION: RELATIONSHIP WITH BNP AND BIOIMPEDANCE

Background: Decompansated heart failure (DHF) is a broad of spectrum of signs and symptoms characterized by fluid’s accumulation in the interstitial space of the lungs and whole body. We evaluate the non-invasive detection of pulmonary capillary wedge pressure (PCWP) by Tissue Doppler Analysis DHF patients underwent treatment with intravenous high-dose furosemide and small-volume hypertonic saline solution (HSS). Moreover we investigate its relationship with changes of BNP plasma levels and Whole-body (WB) and segmental (Seg) bioelectrical impedance analysis (BIA), a non-invasive tool useful to estimate the hydration status and fluid distribution. Methods and Results: 66 consecutive patients (63 to 82 yr, 43 men) admitted for DHF (EF<45%, NYHA class III-IV) underwent tailored therapy with intravenous furosemide and HSS were enrolled. 22 patients with compensated left ventricular dysfunction and 22 healthy subjects were considered as controls. WB and Seg BIA parameters were drawn at hospital entry and after clinical stabilization with treatment. At discharge there was a significant reduction of PCWP (-7 mmHg, p<.001) as BNP levels (p<.001) and significant increase of BIA parameters (p<.001) in DHF patients. Furthermore significant correlations of PCWP with BNP serum levels (p<.001) and BIA parameters (p<.001) and of BNP levels and BIA parameters (p<.001) at baseline and at clinical stabilization correlation were found. Conclusion: our data suggest that non-invasive evaluation of PCWP is a valuable and useful way in management of DHF. Moreover it is related to neuro-hormonal activation and whole-body and pulmonary fluid accumulation in these patients. High-dose of intravenous furosemide plus HSS are well tolerated and improve the in-hospital outcome with an effective hemodynamic stabilization, the normalization of hydration status and a positive neuro-hormonal modulation.

HYPERTONIC 15% SODIUM PYRUVATE OFFERS NO INITIAL RESUSCITATION ADVANTAGE COMPARED WITH 8% HYPERTONIC NACL IN SHEEP WITH MULTIPLE HEMORRHAGES

Initial fluid resuscitation of hemorrhagic shock might be enhanced by the infusion of monocarboxylate-energy substrates. We evaluated hemodynamics, metabolism, and fluid dynamics for initial resuscitation of hemorrhage using small volume 15% sodium pyruvate solution (HPY) compared with osmotically matched 8% hypertonic saline (HS). Instrumented conscious sheep were hemorrhaged 25 mL/kg at time zero through 15 min (T0-T15) and 5 mL/kg for 5 min at T50 to T55 and T70 to T75. Fluid resuscitation from T30 to T180 was performed by a computer-controlled closed-loop system, which titrated infusion rate to a mean arterial pressure of 90 mmHg. Initial infusion was 4 mL/kg of either HPY or HS, followed by the administration of lactated Ringer. Both HPY and HS restored cardiac index similarly. The lactate/pyruvate ratio was used to assess metabolic debt and was significantly higher (T180), whereas oxygen delivery was significantly lower (T120) with HPY versus HS. Total fluid administered was similar, with 43.7 +/- 6.2 mL/kg for HPY and 39.4 +/- 6.8 mL/kg for HS. Plasma volume was similarly increased and approached baseline values for both groups. Initial resuscitation with small volume HPY offered no hemodynamic or metabolic advantage compared with small volume HS when the fluids were infused to an end point pressure.

Hemodynamic effects of combined treatment with oxygen and hypertonic saline in hemorrhagic shock*

In hemorrhagic shock, small volume resuscitation with hypertonic saline transiently increases mean arterial blood pressure (MABP) and cardiac output and augments organ perfusion. Inhalation of 100% oxygen after hemorrhage also increases MABP and redistributes blood flow to the splanchnic and renal vascular beds. We evaluated hemodynamic effects of combined resuscitation with hypertonic saline and oxygen in shock induced by controlled bleeding in rats. Animal study. Research laboratory. Male Sprague-Dawley rats. Animals were assigned to four hemorrhage groups that received posttreatment with a) normal saline; b) normal saline + 100% oxygen; c) hypertonic saline; d) hypertonic saline + oxygen, and a fifth sham-shock group that received hypertonic saline + oxygen. Bolus infusion of small volume hypertonic saline markedly increased MABP (p < .001), hindquarter vascular resistance (p < .05), and distal aorta blood flow (p < .01). Hypertonic saline transiently increased superior (cranial) mesenteric artery (SMA) blood flow (p < .001) and small bowel perfusion (p < .01). Inhalation of oxygen after normal saline rapidly increased MABP (p < .01) and hindquarter vascular resistance (p < .02) and decreased distal aorta blood flow (p < .02) and perfusion of the gracilis muscle (p < .05). When given after normal saline, oxygen did not change SMA resistance and increased SMA flow (p < .05). The supplementation of oxygen after hypertonic saline did not exert additional effects on vascular resistance and blood flows in the two vascular beds. However, the combined treatment prevented the oxygen-induced decrease in distal aorta blood flow and gracilis muscle perfusion and maintained MABP at slightly higher values and SMA flow at significantly higher values than hypertonic saline alone until the end of the protocol (p < .01). The two hemorrhaged groups treated with oxygen exhibited the lowest final plasma lactate concentrations (p < .05 from normal saline and hypertonic saline groups). We suggest that early combined use of hypertonic saline and oxygen exerts a favorable extended profile of hemodynamic effects that amends shortcomings of each treatment alone in hemorrhagic shock.

HSPTX Protects Against Hemorrhagic Shock Resuscitation-Induced Tissue Injury: An Attractive Alternative to Ringer???s Lactate

Conventional fluid resuscitation with Ringer's lactated (RL) activates neutrophils and causes end-organ damage. We have previously shown that HSPTX, a combination of small volume hypertonic saline (HS) and pentoxifylline (PTX), a phosphodiesterase-inhibitor, downregulates in vitro neutrophil activation and proinflammatory mediator synthesis. Herein, we hypothesized that HSPTX decreases end-organ injury when compared with RL in an animal model of hemorrhagic shock. Sprague-Dawley rats were bled to a mean arterial pressure of 35 mm Hg for 1 hour. Animals were divided into 3 groups: sham (no shock, no resuscitation, n = 7), RL (32 mL/kg, n = 7), and HSPTX (7.5% NaCl 4 mL/kg + PTX 25 mg/kg; n = 7). Shed blood was infused after fluid resuscitation. Blood pressure was monitored until the end of resuscitation. Animals were sacrificed at 24 hour after resuscitation. Bronchoalveolar lavage fluid (BALF) was obtained for white cell count (total and differential) and TNF-alpha and IL-1beta levels were measured by ELISA. Lung and intestinal injury at 24 hour were evaluated by histopathology. Organ damage was graded by a pathologist and a score was created (0 = no injury; 3 = severe). Lung neutrophil infiltration was evaluated by MPO immune staining. There were no differences in mean arterial pressure between groups. At 24 hours, BALF leukocyte count was decreased by 30% in HSPTX animals (p < 0.01). TNF-alpha and IL-1beta levels were markedly decreased in HSPTX-resuscitated animals compared with their RL counterparts (p < 0.01). HSPTX-resuscitated animals (lung injury score = 1.0 +/- 0.4) had markedly decreased acute lung injury compared with RL-treated animals (2.5 +/- 0.3) (p < 0.01). RL resuscitation led to a two-fold increase in lung neutrophil infiltration whereas in HSPTX-treated animals, the number of MPO + cells was similar to sham animals (p < 0.001). Intestinal injury was markedly attenuated by HSPTX (1.1 +/- 0.3) compared with RL animals (2.6 +/- 0.4) (p < 0.001). HSPTX, a small volume resuscitation strategy with marked immunomodulatory potential led to a marked decrease in end-organ damage. HSPTX is an attractive alternative to RL in hemorrhagic shock resuscitation.

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

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. 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. 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. 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. 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.

Blood Loss after Fluid Resuscitation with Isotonic or Hypertonic Saline for the Initial Treatment of Uncontrolled Hemorrhage Induced by Spleen Rupture

It has been suggested that fluid resuscitation for the prehospital management of hypotensive trauma victims increases bleeding. In a model of uncontrolled hemorrhage induced by complete splenic laceration with a hilar vascular injury, we hypothesized that small-volume hypertonic saline or large-volume lactated Ringer's solution may provide sustained hemodynamic benefits despite promoting increases in intra-abdominal bleeding. Forty anesthetized, spontaneously breathing dogs (18 +/- 1 kg) underwent laparotomy. A suture line was placed around the spleen to produce a splenic rupture with hilar vascular injury by pulling the exteriorized lines after incision closure. Intra-abdominal blood loss was measured directly, immediately after the animal was killed. Dogs were randomly assigned to four groups (n = 10 per group): Untreated controls were killed 20 (CT20) or 40 (CT40) minutes after splenic rupture to measure blood loss directly. Treatment groups received (20 minutes after spleen rupture) lactated Ringer's (LR), 33 mL/kg over 15 minutes, or 7.5% NaCl/6% dextran 70 (HSD), 4 mL/kg over 4 minutes. Blood loss was measured 40 minutes after spleen rupture. Mean arterial pressure dropped from an average value of 103 +/- 3 mm Hg to 67 +/- 5 mm Hg during the first 20 minutes and was partially restored afterward in all groups, with no significant differences between them. No resuscitation was associated with low cardiac output, whereas HSD restored and LR overshot baseline cardiac output. Intra-abdominal blood loss was 30 +/- 4, 38 +/- 4, 43 +/- 5, and 42 +/- 5 mL/kg for groups CT20, CT40, HSD, and LR, respectively, with no statistical significance between groups. No-fluid resuscitation in uncontrolled hemorrhage from splenic rupture resulted in a low-flow state, whereas resuscitation with small volumes of HSD or large volumes of LR produced hemodynamic benefits without significant increases in bleeding.

803 Effects of high dose furosemide and small-volume hypertonic saline solution infusion in comparison with a high dose of furosemide as bolus, in refractory congestive heart failure. Long term effects

803 Effects of high dose furosemide and small-volume hypertonic saline solution infusion in comparison with a high dose of furosemide as bolus, in refractory congestive heart failure. Long term effects

Effects of high-dose furosemide and small-volume hypertonic saline solution infusion in comparison with a high dose of furosemide as bolus in refractory congestive heart failure: Long-term effects

Background Diuretics have been accepted as first-line treatment in refractory congestive heart failure (CHF), but a lack of response to them is a frequent event. A randomized, single-blind study was performed to evaluate the effects of the combination of high-dose furosemide and small-volume hypertonic saline solution (HSS) infusion in the treatment of refractory New York Heart Association (NYHA) class IV CHF and a normosodic diet during follow-up. Materials and Methods One hundred seven patients (39 women and 68 men, age range 65-90 years) with refractory CHF (NYHA class IV) of different etiologies, who were unresponsive to high oral doses of furosemide, angiotensin-converting enzyme inhibitors, digitalis, and nitrates, were enrolled. Inclusion criteria included an ejection fraction (EF) <35%, serum creatinine level <2 mg/dL, blood urea nitrogen level ≤60 mg/dL, reduced urinary volume, and low natriuresis. The patients were randomized in 2 groups (single-blind). Patients in group 1 (20 women and 33 men) received an intravenous (IV) infusion of furosemide (500-1000 mg) plus HSS (150 mL of 1.4%-4.6% NACl) twice a day in 30 minutes. Patients in group 2 (19 women and 35 men) received an IV bolus of furosemide (500-1000 mg) twice a day, without HSS, during a period lasting 6 to 12 days. Both groups received IV KCl (20-40 mEq) to prevent hypokalemia. At study entry, all patients underwent a physical examination and measurement of body weight (BW), blood pressure (BP), and heart rate (HR), an evaluation of signs of CHF, and measurement of control levels of serum Na, K, Cl, bicarbonate, albumin, uric acid, creatinine, urea, and glycemia daily during hospitalization, and measurements of the daily output of urine for Na, K, and Cl. A chest radiograph, electrocardiogram, and echocardiogram were obtained at study entry, during hospitalization, and at the time of discharge from the hospital. During the treatment and after discharge, the daily dietary Na intake was 120 mmol in group 1 versus 80 mmol in group 2, with a fluid intake of 1000 mL daily in both groups. An assessment of BW and 24-hour urinary volume, serum, and urinary laboratory parameters were performed daily until patients reached a compensated state, when IV furosemide was replaced with oral administration (250-500 mg/d). After discharge from the hospital, patients were observed as outpatients weekly for the first 3 months and, subsequently, once a month. Results The groups were similar in age, sex, EF, risk factors, treatment, and etiology of CHF. All patients showed a clinical improvement. Ten patients in both groups had hyponatremia at entry. A significant increase in daily diuresis and natriuresis was observed in both groups, but it was more significant in the group receiving HSS ( P < .05). The serum Na level increased in group 1 and decreased in group 2 ( P < .05). The serum K level was decreased in both groups ( P < .05). BW was reduced in both groups ( P < .05). Group 2 had an increase in serum creatinine level. Serum uric acid levels increased in both groups. BP values decreased and HR was corrected to normal values in both groups. In the follow-up period (31 ± 14 months), 25 patients from group 1 were readmitted to the hospital for heart failure. In group 2, 43 patients were readmitted tothe hospital at a higher class than at discharge. Twenty-four patients in group 1 died during follow-up, versus 47 patients in group 2 ( P < .001). Conclusion This treatment is effective and well tolerated, improves the quality of life through the relief of signs and symptoms of congestion, and may delay more aggressive treatments. The effects were also beneficial in a long period for mortality reduction (55% vs 13% survival rate) and for clinical improvement. (Am Heart J 2003;145:459-66.)