Intravenous Hypertonic Saline Research Articles

FRI357 A Rare Case Of Paraneoplastic Syndrome Of Inappropriate Secretion Of Antidiuretic Hormone In Oropharyngeal Squamous Cell Carcinoma

Abstract Disclosure: N. Torres: None. H. Rios: None. G. Rios: None. Y. Medina: None. L. Valerio: None. S. Rosa: None. A. Ortiz: None. The syndrome of inappropriate antidiuretic hormone secretion (SIADH) is characterized by hyponatremia that results from water retention attributable to persistent arginine vasopressin release. SIADH is considered the most common cause of euvolemic hyponatremia. Head and neck cancers are linked with 1.5% of SIADH cases. Cases reported in the literature about this association with oropharyngeal squamous cell carcinoma (SCC) were few, and no incidence data is currently available. We present a rare case of a patient with SIADH secondary to well-differentiated oropharyngeal squamous cell carcinoma. A case of 63 y/o male with Oropharyngeal SCC, previous gastrostomy, and tracheostomy due to malignancy. The patient initially presented with general malaise and weakness. Maxillofacial and neck CT scans were remarkable for a mass at the left lateral floor of the mouth, measuring approximately 5.7 cm AP x 2.5 cm transverse x 3.7 cm CC. Physical examination was remarkable for cachexia, but normal skin turgor and moist oral mucosa. An incidental finding of severe hyponatremia of 114 mEq was found. Confirmation of hypotonic euvolemic hyponatremia was performed with a urine osmolality of >100 mOsm per kg and high urine sodium (>40 mEq). These findings presented a strong case for our differential diagnosis of SIADH. Other differential diagnoses were hypothyroidism or adrenal insufficiency. The patient’s thyroid stimulating hormone was within normal levels, and adrenal insufficiency workup was negative, making paraneoplastic SIADH the more likely diagnosis due to SCC. Initial treatment was started with a 3% hypertonic solution drip running at 15 ml/hr. The chemistry panel was monitored every six hours to achieve a 6 mEq change, at a slow rate to avoid osmotic demyelination syndrome, a goal of 122 mEq. Sodium was corrected in 24 hours; 3% saline solution drip was discontinued. Once this level was reached, we continued the fluid restriction (<1L daily), and salt packets with meals. After consultation, Nephrology and Endocrinology services agreed with our diagnosis of hypotonic euvolemic hyponatremia due to ectopic production of paraneoplastic SIADH due to the oropharyngeal SCC. The patient’s hypotonic euvolemic hyponatremia was corrected, symptoms improved, and he was discharged with close follow-up with Hematology/Oncology, Nephrology, and Endocrinology services. Paraneoplastic SIADH due to squamous cell carcinoma is rarely observed in the hospital setting. It is important to consider paraneoplastic SIADH from SCC in the differential diagnosis of hypotonic euvolemic hyponatremia since early diagnosis and treatment can decrease long-term complications. We could have also considered pharmacological therapy for SIADH including the use of demeclocycline, vaptans, and furosemide if the patient had not responded to our interventions. We followed guideline therapy with intravenous hypertonic saline at the start, then transitioned to only using oral salt tablets and fluid restrictions. The patient's hyponatremia steadily improved with our interventions and was able to be discharged with close outpatient follow-up. Presentation: Friday, June 16, 2023

PMON130 Pituitary apoplexy presenting as left basal ganglia hemorrhage

Abstract Introduction The clinical manifestations of pituitary apoplexy (PA) are highly variable and are caused by a rapid increase in the size of intrasellar contents, leading to an increase in intrasellar pressure. Headache, visual disturbances, cranial nerve palsies, and pituitary insufficiency are the most frequent symptoms. Cerebral ischemia and hemorrhage are rare complications of PA. Here we present a case of a young male who presented with left basal ganglia hemorrhagic stroke and pituitary apoplexy. Case Presentation 39-year-old male presented to emergency department for acute onset of nausea, vomiting and right sided weakness for past 2-3 days. Soon after, patient became acutely confused. On examination, he was hypertensive, tachycardiac, tachypneic and obtunded. His pupils were 3 mm, equal, sluggish. He was moving left side but no movements on the right side of his body. In view of rapidly deteriorating mental status, he was intubated for airway protection. Computed tomography (CT) of the head was performed which showed acute left basal ganglia hemorrhage measuring 4.2 cm with vasogenic edema and midline shift of 4 mm. Also noted was markedly expanded sella with a cystic mass containing fluid level measuring up to 4.3 cm. Complete blood count, coagulation profile and liver function tests were unremarkable. His sodium levels were 140 mmol/L, potassium 2.9mmol/L, chloride 101mmol/L and bicarbonate 22 mmol/L. Endocrine workup revealed free T4 0.7 ng/dl, TSH 2.32 mIU/L, FSH 3.0 mIU/ml, LH 4.9 mIU/ml, estradiol 7 pg/ml, testosterone 59 ng/dl, random cortisol 8 ug/dl, ACTH 5.1 pg/ml, growth hormone <0.05 ng/ml, IGF-2 249 ng/ml and prolactin 10,470 ng/ml. MRI brain confirmed hemorrhagic pituitary macroadenoma and left basal ganglia parenchymal hematoma with mass effect and midline shift. Patient was diagnosed with hemorrhagic pituitary macroadenoma causing PA. He was started on intravenous steroids, levothyroxine, cabergoline and hypertonic saline. External ventricular drain was placed for obstructive hydrocephalus followed by left frontal burr hole for hematoma evacuation. Pathology was negative for infection, inflammation, neoplasm and amyloid angiopathy. CT angiography was negative for intracranial aneurysm, arteriovenous malformation, dural arteriovenous fistula, or tumor blushes. He subsequently underwent tracheostomy and gastrostomy placement and transferred to rehabilitation facility. Patient continued to improve neurologically, was subsequently decannulated. Discussion PA is reported to occurs in 2-12% of pituitary adenoma.1 Corticotropic deficiency is common and can be life threatening if left untreated. Empiric steroids should be administered to all patients with signs of PA without waiting for diagnostic confirmation. Intraparenchymal hemorrhage is an extremely rare complication of PA and thought to be related to vasospasm of the cerebral arteries. Reference 1. Briet C, Salenave S, Bonneville JF, et. Al. Pituitary Apoplexy. Endocr Rev. 2015 Dec;36(6): 622-45. doi: 10.1210/er.2015-1042. Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.

Suspected postoperative phenylephrine‐associated pulmonary haemorrhage in a horse with nephrosplenic entrapment of the large colon

AbstractA 16‐year‐old, Irish sport horse was treated with intravenous fluid therapy and phenylephrine, followed by light exercise for a nephrosplenic entrapment of the left large colon. Medical treatment failed to return the colon to its normal position and an exploratory coeliotomy was performed. The surgical procedure and general anaesthesia were uneventfully completed; however, the horse developed haemoptysis, pulmonary oedema and epistaxis in the recovery box. The horse improved after administration of intravenous furosemide and hypertonic saline and was discharged from the hospital 4 days later. Phenylephrine is a sympathomimetic drug that causes splenic contraction and thereby decreases the size of the spleen, allowing the colon to return to its normal position. Fatal pulmonary and abdominal bleeding has been reported as a rare complication of phenylephrine treatment in horses. This case shows a delayed and completely unexpected presentation, which responded to supportive treatment.

Intravenous hypertonic saline to reduce intraocular pressure: the effect of splitting the bolus

To compare intraocular pressure (IOP) and pain after a single versus split bolus of intravenous hypertonic saline (IVHTS). In a prospective, randomized, interventional trial, we enrolled patients with an IOP of 22-34 mmHg. Twenty patients in Group 1 received IVHTS as a single bolus of 1 mmol/kg 23.4% sodium chloride, and 13 patients in Group 2 received two boli of 0.5 mmol/kg separated by 10 min. They graded pain at the infusion site. We measured IOP, heart rate and blood pressure before and 10 and 20 min after IVHTS. Eighteen patients (90%) in Group 1 felt pain (median, 6.5; range, 0-10). In Group 2, 11 patients (85%) felt pain after the first bolus (median, 6.0; range, 0-8) and 12 (92%) after the second one (median, 8; range, 0-10). We found no difference in pain grade between the groups after their first bolus (p = 0.33) or between the first bolus of Group 1 and the second bolus of Group 2 (p = 0.47). The median IOP reduction in Group 1 was 6.5 mmHg (range, 2-16) at 10 min and 7.0 mmHg (range, 4-16) at 20 min (p < 0.001 for both). In Group 2, the corresponding reductions after the second bolus were 9.0 mmHg (range, 4-10; p = 0.002) and 8.0 mmHg (range, 6-11; p = 0.002). The IOP reduction at 10 and 20 min was comparable between groups (p = 0.094 and p = 0.41, respectively). Splitting the bolus did not reduce pain associated with IVHTS. Single bolus is consequently recommended.

Induced hypernatremia in patients with moderate-to-severe ARDS: a randomized controlled study

BackgroundInduced hypernatremia and hyperosmolarity is protective in animal models of lung injury. We hypothesized that increasing and maintaining plasma sodium between 145 and 150 mmol/l in patients with moderate-to-severe ARDS would be safe and will reduce lung injury. This was a prospective randomized feasibility study in moderate-to-severe ARDS, comparing standard care with intravenous hypertonic saline to achieve and maintain plasma sodium between 145 and 150 mmol/l for 7 days (HTS group). Both groups of patients were managed with lung protective ventilation and conservative fluid management. The primary outcome was 1-point reduction in lung injury score (LIS) or successful extubation by day 7.ResultsForty patients were randomized with 20 in each group. Baseline characteristics of severity of illness were well balanced. Patients in the HTS group had higher plasma sodium levels during the first 7 days after randomization when compared with the control group (p = 0.04). Seventy five percent (15/20) of patients in the HTS group were extubated or had ≥ 1-point reduction in LIS compared with 35% (7/20) in the control group (p = 0.02). There was also a decrease in length of mechanical ventilation and hospital length of stay in the HTS group.ConclusionWe have shown clinical improvement in patients with moderate-to-severe ARDS following induced hypernatremia, suggesting that administration of hypertonic saline is a safe and feasible intervention in patients with moderate-to-severe ARDS. This suggests progress to a phase II study.Clinical Trial Registration Australian and New Zealand Clinical Trials Registry (ACTRN12615001282572)

Wheezing in preschool children: New perspective.

In recent years the understanding about the mechanism of development of wheezing in children has improved and various management strategies were tried by different researchers. A search was made in PubMed by putting search term ‘Recurrent Wheezing in Children Diagnosis and Management’ and ‘Recurrent Wheezing in Children’. The respiratory syncytial virus induced bronchiolitis and rhinovirus infection in preschool children may lead to recurrent wheezing in preschool children. In infant immune system is immature and depends mainly on TLR ligation and maternal derived antibodies. Anti-inflammatory cytokines such as IL-10 and TGF beta are more common. RSV NS1 and NS2 proteins target RLR and TLR 3 dependent signaling and suppress the cellular response to RSV replication .This can lead to Th2 like response leading to asthma and allergy. CDHR3 acts as receptor in rhinovirus C infection. RV infection causes increase in IL 25 and IL 33 both induce Th2 type of immunity by increasing IL5 and IL 13 Daily Inhaled Corticosteroids (ICS) have been found useful in preventing exacerbations. Evidence is inconclusive about intermittent inhaled corticosteroids, intermittent montelukast and daily montelukast in recurrent wheezing. Azithromycin started early may decrease duration of wheezing episode. About intravenous magnesium sulfate and hypertonic saline evidence is inconclusive. Vitamin D supplementation in preterm babies for 6 months and avoidance of cow’s milk for first three days of life may be useful in prevention of recurrent wheezing in preschool children.

Hyperdipsia in sheep bearing lesions in the medial septal nucleus

Previous experiments in rodents showed that ablation of the septal brain region caused hyperdipsia. We investigated which part of the septal region needs ablation to produce hyperdipsia in sheep, and whether increased drinking was a primary hyperdipsia. Following ablation of the medial septal region (n = 5), but not parts of the lateral septal region (n = 4), daily water intake increased from ~2.5–5 L/day up to 10 L/day for up to 3 months post-lesion. In hyperdipsic sheep, plasma osmolality increased on the first day post-lesion and body weight fell, suggesting that initial hyperdipsia was secondary to fluid loss. However hyperosmolality was not sustained long-term and plasma hypo-osmolality persisted from 0.5 to 3 months post-lesion. Acute dipsogenic responses to intravenous hypertonic saline, intravenous or intracerebroventricular angiotensin II, water deprivation for 2 days, or feeding over 5 h were not potentiated by medial septal lesions, showing that the rapid pre-systemic inhibitory influences that cause satiation of thirst upon the act of drinking were intact. However, hyperdipsic sheep continued to ingest water when hyponatremic (plasma [Na] was 127–132 mmol/l) and plasma osmolality was 262–268 mosmol/kg due to retention of ingested fluid resulting from intravenous infusion of vasopressin administered to maintain a basal blood level of antidiuretic hormone. The results show that septal lesion-induced hyperdipsia is not due to disruption of acute pre-systemic influences associated with drinking water that initiates rapid satiation of thirst. Rather, inhibitory influences of hyponatremia, hypo-osmolality or hypervolemia on drinking appear to be disrupted by medial septal lesions.

Hypertonic Saline For The Treatment of Diuretic Resistance In Advanced Heart Failure: A Retrospective Analysis From The Cleveland Clinic

Background Recent studies demonstrated that intravenous hypertonic saline solution (HSS) in combination with high-dose furosemide for the management of diuretic resistance in heart failure can lead to improved diuresis, reduction in length of hospitalization and mortality. Objective The objective of this study was to analyze real world use and safety of HSS administration in advanced heart failure patients in the Cleveland Clinic and identify factors for improvement for the development of an institutional protocol. Methods A retrospective chart analysis was performed in all advanced heart failure patients in whom HSS was administer and who were admitted to the intensive heart failure care unit from 2008 to 2019. Results In our study cohort of 34 patients who received HSS (median age 64 [IQR 53,68] years, 56% male, median LVEF 23 [IQR 15,39]%, median Cr 1.4 [IQR 1.1,2.1]mg/dL, median Na 121 [IQR 116,125]mg/dL), all subjects except one received 3% sodium chloride as HSS regimen. There was large variability in amount of NaCl administered (median 5,5 [IQR 3.4,18]g), infusion speed (median 50 [25,71]ml/min) and concurrent intravenous administration of loop diuretics (75%) and their dosages (furosemide median dose 240 [100-490]mg). The change in serum sodium serum sodium (3 [IQR 1, 5] mmol/L) after HSS was significant (p Conclusion Hypertonic saline solution administered has largely restricted to a relatively small cohort of end-stage heart failure patients with significant hyponatremia, and demonstrated increase in serum sodium without detrimental effects on renal function or complications related to sodium repletion or volume overload. However, the lack of a standardized precluded meaningful assessment of safety and efficacy of such interventions.

The impact of hypertonic saline on cerebrovascular reactivity and compensatory reserve in traumatic brain injury: an exploratory analysis.

BackgroundIntravenous hypertonic saline is utilized commonly in critical care for treatment of acute or refractory elevations of intracranial pressure (ICP) in traumatic brain injury (TBI) patients. Though there is a clear understanding of the general physiological effects of a hypertonic saline solution over long periods of time, smaller epoch effects of hypertonic saline (HTS) have not been thoroughly analyzed. The aim of this study was to perform a direct evaluation of the high-frequency response of HTS on the cerebrovascular physiological responses in TBI.MethodsWe retrospectively reviewed our prospectively maintained adult TBI database for those with archived high-frequency cerebral physiology and available HTS treatment information. We evaluated different epochs of physiology around HTS bolus dosing, comparing pre- with post-HTS. We assessed for changes in slow fluctuations in ICP, pulse amplitude of ICP (AMP), cerebral perfusion pressure (CPP), mean arterial pressure (MAP), cerebrovascular reactivity (as measured through pressure reactivity index (PRx)), and cerebral compensatory reserve (correlation (R) between AMP (A) and ICP (P)). Comparisons of mean measures and percentage time above clinically relevant thresholds for the physiological parameters were compared pre- and post-HTS using descriptive statistics and Mann-Whitney U testing. We assessed for subgroups of physiological responses using latent profile analysis (LPA).ResultsFifteen patients underwent 69 distinct bolus infusions of hypertonic saline. Apart from the well-documented decrease in ICP, there was also a reduction in AMP. The analysis of cerebrovascular reactivity response to HTS solution had two main effects. For patients with grossly impaired cerebrovascular reactivity pre-HTS (PRx > + 0.30), HTS bolus led to improved reactivity. However, for those with intact cerebrovascular reactivity pre-HTS (PRx < 0), HTS bolus demonstrated a trend towards more impaired reactivity. This indicates that HTS has different impacts, dependent on pre-bolus cerebrovascular status. There was no significant change in metrics of cerebral compensatory reserve. LPA failed to demonstrate any subgroups of physiological responses to HTS administration.ConclusionsThe direct decrease in ICP and AMP confirms that a bolus dose of a HTS solution is an effective therapeutic agent for intracranial hypertension. However, in patients with intact autoregulation, hypertonic saline may impair cerebral hemodynamics. These findings regarding cerebrovascular reactivity remain preliminary and require further investigation.Electronic supplementary materialThe online version of this article (10.1007/s00701-020-04579-0) contains supplementary material, which is available to authorized users.

Evaluation of the use of Hypertonic Saline 3% Nebulizer versus Intravenous Hypertonic Saline 3% to Attenuate the Manifestations of Acute Respiratory Distress Syndrome

Background: A well-known disease, Acute Respiratory Distress Syndrome (ARDS) presents a daunting challenge to the medical community with alarmingly high mortality rates. Initiation of hypertonic saline (HTS) nebulization therapy for patients with early ARDS appears to be tolerable and may be beneficial. However, using a nebulizer is cumbersome and less efficient. This study aims to assess the efficacy of using HTS3% in a nebulizer in comparison with intravenously injecting it to attenuate the manifestation of ARDS. The study analyses factors such as the severity of the disease, need and duration of mechanical ventilation (MV), ICU stay, and mortality rate in the comparative analysis. Materials and Methods: The randomized, comparative, and controlled study included patients of both genders from an age bracket of 18-60 years. The patients fulfilled the Berlin definition of ARDS. Additionally, the whole sample was divided into four groups (26 patients each): Group A received standard pharmacotherapy [methylprednisolone 1mg/kg/day intravenously and salbutamol nebulizer 2.5 mg (1 ml) + 3 ml normal saline/8hr] and normal saline 0.9% (5ml) nebulizer /8hr: Group B received standard pharmacotherapy + HTS2.7% (5ml) nebulizer/8hr: Group C also received standard pharmacotherapy and 500ml normal saline intravenously over 24 hours: Group D received standard pharmacotherapy and 500 ml HTS 3% intravenously over 24 hours. The following parameters were recorded: Lung injury score (Murray Score, calculated every 24 hours), the incidence of the need for MV, duration of MV, length of ICU stay, and mortality rate. Results: Group B (HTS nebulizer group) and group D (HTS IV group) showed the most rapid improvement in the Murray score with a 50% decrease in the score from its initial value (D50%) by day 4 with P-values of 0.013 and 0.022 respectively. Subjects from Group D (HTS IV) and Group B (HTS Nebulizer) were the least in need of MV as only 38.5% needed MV with a P-value &lt;0.001. In comparison, 69.2% subjects from group A (control) and 73.1% from group C required MV, with a P-value &lt;0.001. The shortest duration of MV care was found in group D (median 3.12 days), followed by group B (median 4.21 days). The results were highly significant, with P-value 0.004 when compared with group A (control group) and group C. In addition, the longest duration of MV care was reported in group A (median 5.37 days). There was significant variation in all groups regarding the length of ICU stay: group D required the least number of days (median 6.76 days), followed by group B (median 7.08 days). The result was statistically significant, with a P-value of 0.004 when compared with the control group (median 9.1 days) and group C(longest duration of MV with a median of 10.13 days). However, no significant difference was found in the mortality rate (P-value &gt;0.05). Conclusion: The use of hypertonic saline 3% intravenously has a comparable effect as the use of hypertonic saline 3% via nebulizer to attenuate the manifestations of (ARDS) and even superior in the mechanically ventilated patient.

SUN-185 Severe Hyponatremia and Type 4 Renal Tubular Acidosis (Functional Hypoaldosteronism) Secondary to Trimethoprim

Introduction:Trimethoprim-sulfamethoxazole (TMP-SMX) is a commonly used antibiotic. We present a case of severe hyponatremia and Type 4 renal tubular acidosis (functional hypoaldosteronism) in a patient treated with TMP-SMX.Clinical Case:A 62 year old gentleman with hypertension, dyslipidemia and a surgically repaired abdominal aortic aneurysm developed an aortic graft infection. He was admitted to hospital for acute right lower limb ischemia with embolic phenomena, and underwent surgical graft explantation. He required multiple courses of antibiotics post operatively.He was initially referred to Endocrinology for severe hyponatremia, deemed likely to be from a salt losing nephropathy secondary to polymyxin. Thyroid function and morning cortisol levels were normal. He was managed with intravenous hypertonic saline and oral salt tablets. The hyponatraemia resolved a week after polymyxin was stopped.Intravenous TMP-SMX was commenced the next day at 240 mg BD. A week later, the hyponatremia recurred, with concomitant hyperkalemia and a normal anion gap metabolic acidosis.The serum sodium was 126 mmol/L (reference interval (RI) 135-145) and the serum osmolality 275 mmol/kg (RI 275- 305). Urine studies showed a high urinary sodium (154 mmol/L) and osmolality (481 mmol/kg), consistent with renal salt wasting. The serum potassium rose to a peak of 6.1 mmol/L (RI 3.5 - 5.0), with a normal anion gap metabolic acidosis (bicarbonate 17 mmol/L (RI 21 – 31)). A paired urine pH of 8 pointed to an inability to acidify the urine.Given the clinical course and laboratory investigations, the diagnosis of TMP-associated hyponatremia and Type 4 RTA was made. Oral resonium was started to correct hyperkalemia, with a combination of oral sodium chloride and sodium bicarbonate used to treat the hyponatremia and metabolic acidosis. Fludrocortisone was not used given the concerns of causing hypertension in a patient with a diseased aortic graft.The dose of TMP-SMX was gradually reduced with improvement of the acid-base and electrolyte abnormalities, lending weight to our diagnosis. After the dose of the TMP-SMX was reduced to 80 mg BD, the hyperkalemia and metabolic acidosis resolved. The oral sodium chloride and sodium bicarbonate were gradually tailed off and stopped after cessation of the TMP-SMX.Clinical Lesson:Trimethoprim blocks the epithelial sodium channel (ENaC) of the principal cells in the terminal portion of the nephron, similar to potassium sparing diuretics like amiloride and triampterene. The resulting hyponatremia, hyperkalemia and metabolic acidosis can be life threatening. Therefore, monitoring of electrolytes and acid base status is important, particularly in susceptible patients or in those where a high dose of trimethoprim is required.

HYPOREFLEXIA, HYPOTONIA, AND HYPONATREMIA: A CASE OF GUILLAIN-BARRÉ SYNDROME AND SIADH

SESSION TITLE: Wednesday Fellows Case Report Posters SESSION TYPE: Fellow Case Report Posters PRESENTED ON: 10/23/2019 09:45 AM - 10:45 AM INTRODUCTION: Guillain-Barré Syndrome (GBS) is an acute inflammatory radiculoneuropathy that is characterized by acute or subacute areflexic paralysis with albumin-cytologic dissociation evident on cerebrospinal fluid (CSF) analysis. In patients with critical neurologic disease, hyponatremia is one of the most severe metabolic complications. Even with mild hyponatremia the consequences can be grave ranging from severe neurologic deficits to death. The association between hyponatremia and GBS has been reported in the past, however, the underlying pathophysiology is not completely understood. CASE PRESENTATION: A 57-year-old female presented to the emergency department due to bilateral distal extremity weakness, worse in the lower extremities, and unsteady gait. The patient stated that her symptoms progressed over the last week with significant numbness, tingling, and weakness bilaterally and difficulty walking. Other than a recent upper respiratory tract infection, she had not experienced any other changes in lifestyle or medications. Upon arrival, CT and MRI of the head and spine were negative for acute changes. Initial labs were within normal limits. Lumbar puncture was performed and the patient was noted to have a CSF protein of 116 mg/dL, WBC 2 per μL, RBC 6 per μL, and glucose 65 mg/dL. Based on these results, the patient was diagnosed with GBS. Over the next 24 hours, the patient’s sodium level dropped from 136 to 119 mEq/L. Urine sodium was greater than 40 mEq and serum osmolality was 248 mOsm/kg. Intravenous immunoglobulin (IVIG) and hypertonic saline were initiated. Over the next 4 days the patient’s hyponatremia resolved with the initiation of fluid restriction and hypertonic saline. Her neurologic symptoms substantially improved prior to discharge. DISCUSSION: The incidence of hyponatremia in GBS patients is reported to be as high as 48% and is typically present in more severe cases. The mechanism of hyponatremia is usually attributed to syndrome of inappropriate secretion of antidiuretic hormone (SIADH) and has been documented as an initial symptom prior to flaccid paralysis. The association between SIADH and GBS is attributed to hypothalamic inflammation. Risk factors for hyponatremia in the setting of GBS include: age > 50 years and preexisting co-morbidities including anemia, alcohol abuse, hypertension, and coagulopathy. Administration of IVIG is associated with a 33% increased likelihood of hyponatremia in patients with GBS. It has been demonstrated that hyponatremia is an indicator of more severe pathology regardless of the underlying disease. CONCLUSIONS: Hyponatremia can occur in the setting of GBS, typically in association with severe clinical states. Although SIADH is the most common cause of hyponatremia in GBS, the exact underlying pathophysiology is unknown. Treatment should be directed at the underlying cause. Reference #1: Sejvar JJ. Population incidence of GBS: a systematic review and meta-analysis. Neuroepidemiology. 2011;36:123-33 Reference #2: Hiew F, Winer J, Rajabally Y. Hyponatremia in Guillain-Barre syndrome revisited. Acta Neurol Scand. 2015;133:295-301. Reference #3: Rabinstein AA. Hyponatremia in critically ill neurological patients. Neurologist. 2003;290-300. DISCLOSURES: No relevant relationships by Hussein Asad, source=Web Response No relevant relationships by Daniel Griffin, source=Web Response

SUN-435 SIADH Precipitated by Pneumonia in a Background of Hypothyroidism and SSRI Use

Introduction: Hyponatremia is serum sodium levels below 135 meq/L. SIADH is a disorder of impaired water excretion caused by the inability to suppress the secretion of ADH leading to hyponatremia. Important causes of hyponatremia are heart failure, cirrhosis, diuretic induced, hypothyroids, cortisol deficiency and SIADH. Causes of SIADH are CNS disorders, malignancies, surgery, pulmonary disease (particularly pneumonia), hormone deficiency (both hypopituitarism, hypothyroidsm), HIV, drugs- esp. SSRIs. Clinical Case: 74 y/o F with past medical history of Diabetes, HTN, hypothyroidism, depression and chronic compensated hyponatremia under carvedilol, losartan, levothyroxine, citalopram, presented to ER with SOB with wheezing. Patient was admitted for pneumonia and treated with azithromycin and ceftriaxone. In Day 2, he developed intractable nausea and vomiting despite zofran and phenargan. IV NS was started. Patient developed hyponatremia, Na of 126 mEq/L, serum osmolality 240, Urine osm 457 mOsm/, TSH was 41 mIU/L. Levothyroxine was increased to 175 mcg. Fluid & Citalopram was stopped. Na was closely monitored. Over the next few days, patient and Na levels slowly improved with fluid restriction and Na tablets. Conclusion: Not all hyponatremia is SIADH while SIADH is a cause of hyponatremia. The diagnosis is often confusing. SIADH should be suspected in any patient with serum Na <135 mmol/L, serum osmolality <280 mOsm, and a inappropriate and relatively high urine osmolality (compared to serum osmolality). SIADH is more common in patients above age 65 years. Finding out the cause and fluid restriction is the mainstay of treatment in SIADH. Exception to this is brain surgeries & Sub Arachnoid Hemorrhage where there may be ongoing cerebral salt wasting and, fluid restriction can be deleterious as it can cause cerebral vasospasm. However for most cases of non-SIADH hyponatremia, Sodium chloride, (oral tablet or isotonic saline) is the therapy. Other ways to treat hyponatremia would be treating the underlying cause, restricting water intake or vasopressin receptor antagonist. For severe case (with seizure and severe neurological abnormalities) of any hyponatremia, intravenous hypertonic saline is the choice.

The effect of 3 resuscitative fluid therapies on hemostasis as measured by rotational thromboelastometry in dogs.

Evidence suggests that administration of intravenous fluids impairs hemostasis. Thromboelastometry (TEM) may provide a more sensitive measure of the fluid effects on hemostasis than traditional coagulation tests. The study aim was to determine if resuscitative fluid therapy affects hemostasis, as measured by TEM. Using a randomized crossover design, 6 healthy dogs were administered intravenous colloid, crystalloid, and hypertonic saline at therapeutic doses. Whole blood samples were taken at baseline, 1, 4, and 8h posttreatment for TEM analysis and measurement of PT, APTT, and fibrinogen. Univariate ANOVA on transformed data evaluated differences between groups and within groups. When significant differences were noted (P = .003), a Tukey test was performed. A statistically significant interaction between individual dogs and treatment was noted for most TEM variables. There was a significant decrease in clot firmness from baseline in the TEM assessment of the intrinsic pathway. Colloid treatment correlated with significantly higher clot firmness in the TEM extrinsic pathway assessment, which decreased over time, and PT was significantly shorter in colloid-treated dogs. Overall, PT was significantly prolonged at one hour; however, all PT values were within the RI. The fibrinogen concentration was significantly different between all treatments. Clinically relevant doses of resuscitative fluids resulted in a decreased clot firmness in the intrinsic pathway, as measured by TEM, which affected hemostatic variables in healthy dogs. There was also a significant individual response to treatment. The changes noted in this study are not expected to result in clinically apparent bleeding.

Heat-related illness in the African wilderness

Wilderness heat-related illnesses span a variety of conditions caused by excessive or prolonged heat exposure, and/or the inability to compensate adequately for increased endogenous production during strenuous outdoor activities. Despite management of well-known risk factors, such as lack of fitness or acclimatisation, dehydration, underlying illness and certain medications, even highly trained individuals may exceed their physiological capability to dissipate increased core temperature. Heat illnesses range from benign cramps to the more concerning heat syncope and exercise-associated collapse (with or without hyperthermia), and culminate in life-threatening heat stroke. The differential diagnosis in the wilderness is broad and should include exercise-associated hyponatraemia with or without encephalopathy. Clinical guidelines for wilderness and hospital management of these conditions are available. Field management and evacuation are based on severity, and include cooling, rehydration and assessment of core temperature and serum sodium, if possible. Hyponatraemia should be corrected with the use of oral or intravenous hypertonic saline, depending on whether the patient can safely take oral fluids. Hospital management may include aggressive and potentially invasive cooling, careful assessment for organ dysfunction, and intensive multi-organ support, if required. Paracetamol, non-steroidal anti-inflammatory drugs and dantrolene should not be used.

Abstract WP351: No Effect of Mannitol on the Course of Perihemorrhagic Edema After Intracerebral Hemorrhage

Introduction: In patients with intracerebral hemorrhage (ICH) perihemorrhagic edema (PHE) seems to play a predictive role besides initial hematoma size, clinical status and intraventricular bleeding (IVH). PHE may exceed the initial hematoma volume by up to 600% thereby leading to increased intracranial pressure (ICP) which may cause severe clinical deterioration. EUSI and ASA guidelines recommend the use of intravenous mannitol or hypertonic saline (HS) in order to reduce elevated ICP. However, clinical data suggest that HS may be superior to mannitol in lowering ICP and clinical data concerning the effect of mannitol on PHE as a cause of elevated ICP is limited. We aimed to investigate the effect of mannitol on PHE after ICH. Methods: Patients with supratentorial spontaneous ICH treated with 20% intravenous mannitol solution (125-250ml every 6h) for 5-10 days and controls matched for ICH volume, age and IVH who did not receive any osmotic agents during the course of treatment were identified retrospectively from our institutional ICH database. PHE volume was calculated on diagnostic CT scans performed on days 1, 2-3, 4-6, 7-9 and 10-12 using a validated volumetric algorithm. Frequency of elevated ICP up to day 12 (ICP burden), modified Rankin Scale (mRS) after rehabilitation (approx. day 90) and PHE evolution were assessed as outcome variables. Results: 44 ICH patients treated with mannitol and 43 controls were included. Basic characteristics did not differ between groups (median ICH volume day 1: 32.9 mL (IQR 16.3 - 54.0) and 27.7 mL (IQR 22.4 - 37.1), p=0.786; median age 71 y (IQR 61.5 - 77) and 72 y (IQR 66 - 81), p=0.269; median PHE volume day 1: 24.3 mL (IQR 16.0 - 38.8) and 24.3 mL (IQR 17.1 - 32.1), p=0.592, respectively). In the mannitol group PHE volume exceeded to a greater extent than in controls (PHE on day 10-12: 60.1 mL (SD 33.6) vs. 36.8 mL (SD 23.2), p=0.005). Median ICP burden was higher in the mannitol group (0 (IQR 0 - 7.75) vs. 0 (IQR 0), p=0.016). Median mRS did not differ between both groups (4 (IQR 4-6) vs. 4 (IQR 3-6), p=0.321). Conclusions: We found no effect of mannitol use on the general evolution of PHE and ICP. Other underlying mechanisms may explain the short-term effect of mannitol bolus administration on ICP in patients with spontaneous supratentorial ICH.

Hypertonic Saline: Safe therapy for Children with cute Brain Insult in Emergency Department of Low and Middle Income Country

Hypertonic saline (HTS) has been used for some years to treat elevated intracranial pressure in children in high income countries. There is limited safety data from low and middle income countries. Objective: The primary objective of this study was to assess the immediate response and safety of intravenous administration of hypertonic saline in children with acute brain injury presenting to the pediatric emergency department (PED) of Aga Khan University Hospital (AKUH). The secondary outcomes were changes in outcome- predictive physiological parameters. Methods: A retrospective, chart review of children who received intravenous HTS in the pediatric emergency department of AKU between January 2013 and December 2013 to treat acute brain injury (ABI). We studied both changes in physiological parameters and adverse effects related to HTS therapy. Results: In the period studied, 216 children received intravenous bolus of 3% HTS as part of their initial management in the PED. The median age of the patients was 6.1 years (1 month to 16 years) and a median dose of 5 mL/kg with 98% of doses given via peripheral line between 30 minutes to one hour. Diagnosis included traumatic brain injury in 110 patients (50.9%) and non-traumatic injury 106 (49.1%) including CNS infection (43.4%), intracranial bleeding (7.5%), acute hepatic failure (10.4%), diabetic ketoacidosis with altered mental status (4.7%). Clinical indications included: depressed consciousness (75.5%), seizures (24%) and shock (0.5%). Significant improvement was observed in both heart rate (p value < 0.05) and GCS (p value=0.001) after 3% HTS therapy No adverse events related to the HTS or its route of administration were noted in any child. Conclusion: We found 3% HTS was safe in children with acute brain injury traumatic or non–traumatic brain injury.

Immune-Inflammatory and Metabolic Effects of High Dose Furosemide plus Hypertonic Saline Solution (HSS) Treatment in Cirrhotic Subjects with Refractory Ascites.

IntroductionPatients with chronic liver diseases are usually thin as a result of hypermetabolism and malnutrition expressed by reduced levels of leptin and impairment of other adyponectins such as visfatin.AimsWe evaluated the metabolic and inflammatory effects of intravenous high-dose furosemide plus hypertonic saline solutions (HSS) compared with repeated paracentesis and a standard oral diuretic schedule, in patients with cirrhosis and refractory ascites.Methods59 consecutive cirrhotic patients with refractory ascites unresponsive to outpatient treatment. Enrolled subjects were randomized to treatment with intravenous infusion of furosemide (125–250mg⁄bid) plus small volumes of HSS from the first day after admission until 3 days before discharge (Group A, n:38), or repeated paracentesis from the first day after admission until 3 days before discharge (Group B, n: 21). Plasma levels of ANP, BNP, Leptin, visfatin, IL-1β, TNF-a, IL-6 were measured before and after the two type of treatment.ResultsSubjects in group A were observed to have a significant reduction of serum levels of TNF-α, IL-1β, IL-6, ANP, BNP, and visfatin, thus regarding primary efficacy endpoints, in Group A vs. Group B we observed higher Δ-TNF-α, Δ-IL-1β, Δ-IL-6, Δ-ANP, Δ-BNP, Δ-visfatin, Δ-Leptin at discharge.DiscussionOur findings underline the possible inflammatory and metabolic effect of saline overload correction in treatment of cirrhosis complications such as refractory ascites, suggesting a possible role of inflammatory and metabolic-nutritional variables as severity markers in these patients.

Treatment of Acute Liver Failure in Resource-Constrained Settings without Transplantation Facilities Can Be Improved.

Treatment of Acute Liver Failure in Resource-Constrained Settings without Transplantation Facilities Can Be Improved.

Impaired sodium-evoked paraventricular nucleus neuronal activation and blood pressure regulation in conscious Sprague-Dawley rats lacking central Gαi2 proteins.

AimWe determined the role of brain Gαi2 proteins in mediating the neural and humoral responses of conscious male Sprague–Dawley rats to acute peripheral sodium challenge.MethodsRats pre‐treated (24‐h) intracerebroventricularly with a targeted oligodeoxynucleotide (ODN) (25 μg per 5 μL) to downregulate brain Gαi2 protein expression or a scrambled (SCR) control ODN were challenged with an acute sodium load (intravenous bolus 3 m NaCl; 0.14 mL per 100 g), and cardiovascular parameters were monitored for 120 min. In additional groups, hypothalamic paraventricular nucleus (PVN) Fos immunoreactivity was examined at baseline, 40, and 100 min post‐sodium challenge.ResultsIn response to intravenous hypertonic saline (HS), no difference was observed in peak change in mean arterial pressure between groups. In SCR ODN pre‐treated rats, arterial pressure returned to baseline by 100 min, while it remained elevated in Gαi2 ODN pre‐treated rats (P < 0.05). No difference between groups was observed in sodium‐evoked increases in Fos‐positive magnocellular neurons or vasopressin release. V1a receptor antagonism failed to block the prolonged elevation of arterial pressure in Gαi2 ODN pre‐treated rats. A significantly greater number of Fos‐positive ventrolateral parvocellular, lateral parvocellular, and medial parvocellular neurons were observed in SCR vs. Gαi2 ODN pre‐treated rats at 40 and 100 min post‐HS challenge (P < 0.05). In SCR, but not Gαi2 ODN pre‐treated rats, HS evoked suppression of plasma norepinephrine (P < 0.05).ConclusionThis highlights Gαi2 protein signal transduction as a novel central mechanism acting to differentially influence PVN parvocellular neuronal activation, sympathetic outflow, and arterial pressure in response to acute HS, independently of actions on magnocellular neurons and vasopressin release.