Retrospective evaluation of sodium acetate use for urine alkalinization in patients receiving high dose methotrexate.

PURPOSE: Methotrexate is an antifolate agent used in treatment of several malignancies. Many toxicities accompany methotrexate that are minimized with urine alkalinization. Parenteral sodium bicarbonate is the historical standard alkalinizing agent, but use has been limited by intermittent shortages. However, intravenous sodium acetate may be considered as a chemically equivalent alternative. The primary objective of this study is to determine the efficacy of sodium acetate versus sodium bicarbonate for urine alkalinization for high-dose methotrexate (HDMTX). METHODS: This is a retrospective cohort study including adults admitted to Barnes-Jewish Hospital to receive HDMTX for lymphoma, breast cancer with leptomeningial spread, or osteosarcoma. Patients must have received intravenous sodium acetate or sodium bicarbonate alkalinization. RESULTS: Of 192 HDMTX encounters, 154 (sodium bicarbonate, n = 86; sodium acetate, n = 68) were evaluated for efficacy and safety. Safety outcomes were not significantly different between groups except for higher peak methotrexate level in the bicarbonate group (2.9 mcmol/L vs. 1.7 mcmol/L, p = 0.023), and increased incidence of grade 3-4 ALT in the sodium bicarbonate group (23.5% vs. 9%, p = 0.02). Time from alkalinizer initiation to pH ≥7 was significantly shorter with sodium bicarbonate (4 vs. 5.15 h, p = 0.021). Nonetheless, outcomes such as length of stay (4.4 vs. 4 days respectively, p = 0.037) and time to methotrexate clearance (3.6 vs. 3.2 days respectively, p = 0.023) reveal that inpatient time was shorter with sodium acetate overall. CONCLUSION: This retrospective analysis suggests that sodium acetate has similar efficacy and safety to sodium bicarbonate for alkalinization and may be considered as an alternative in future shortage situations.

One-Pot Synthesis of Novel Hydrazono-1,3-Thiazolidin-4-One Derivatives as Anti-HIV and Anti-Tubercular Agents: Synthesis, Biological Evaluation, Molecular Modelling and Admet Studies.

BACKGROUND: The necessity for newer anti-HIV and anti-tubercular medications has arisen as a result of the prevalence of opportunistic infections caused by HIV (human immunodeficiency virus). OBJECTIVE: A series of ten new hydrazono 1,3-thiazolidin-4-one derivatives were synthesized in one-pot and evaluated for anti-HIV and anti-tubercular activities. Molecular Docking was accomplished with HIV-1 reverse transcriptase protein (PDB ID: 1REV) and Mycobacterium Tuberculosis (M. tuberculosis) H37Rv protein (PDB ID: 2YES) receptors along with drug-likeness and ADMET properties. METHODS: One-pot synthesis of hydrazono 1,3-thiazolidin-4-one derivatives was carried out by ketones, thiosemicarbazide and ethylchloroacetate with the catalyst of anhydrous sodium acetate. All the synthesized compounds were characterized and evaluated for their in-vitro anti-HIV and also evaluated for their in-vitro anti-tubercular activity against M. tuberculosis H37Rv. In-silico predicted physicochemical parameters were done by MedChem DesignerTM software version 5.5 and ADMET parameters by pkCSM online tool. Furthermore, molecular docking was performed with pyrx 0.8 by autodock vina software. RESULTS: All the synthesized compounds were characterized and evaluated for their in-vitro anti- HIV activity for inhibition of syncytia formation, which shows KTE1 with EC50 47.95 µM and Selectivity Index (SI) of >4.17 and for inhibition of p24 antigen production EC50 was found to be 80.02 µM and SI of >2.49. The compounds were also evaluated for their in-vitro anti-tubercular activity against M. tuberculosis H37Rv, in which KTE1 MIC values of 12.5µg/ml with SI of >4.0 and cytotoxicity against Vero cell lines. In-silico predicted physicochemical parameters for synthesized compounds which were found to be drug-like. Furthermore, docking has shown a good dock score and binding energy with anti-HIV and anti-tubercular receptors. CONCLUSION: From the novel synthesized molecules, none of the molecule is as effective as standards for anti-HIV and anti-tubercular drugs and hence can be further explored for its potential activities. Furthermore, derivatization was made to achieve more potent compounds for anti-HIV and anti-tubercular drugs.

Balanced Multielectrolyte Solution versus Saline in Critically Ill Adults.

BACKGROUND: Whether the use of balanced multielectrolyte solution (BMES) in preference to 0.9% sodium chloride solution (saline) in critically ill patients reduces the risk of acute kidney injury or death is uncertain. METHODS: In a double-blind, randomized, controlled trial, we assigned critically ill patients to receive BMES (Plasma-Lyte 148) or saline as fluid therapy in the intensive care unit (ICU) for 90 days. The primary outcome was death from any cause within 90 days after randomization. Secondary outcomes were receipt of new renal-replacement therapy and the maximum increase in the creatinine level during ICU stay. RESULTS: A total of 5037 patients were recruited from 53 ICUs in Australia and New Zealand - 2515 patients were assigned to the BMES group and 2522 to the saline group. Death within 90 days after randomization occurred in 530 of 2433 patients (21.8%) in the BMES group and in 530 of 2413 patients (22.0%) in the saline group, for a difference of -0.15 percentage points (95% confidence interval [CI], -3.60 to 3.30; P = 0.90). New renal-replacement therapy was initiated in 306 of 2403 patients (12.7%) in the BMES group and in 310 of 2394 patients (12.9%) in the saline group, for a difference of -0.20 percentage points (95% CI, -2.96 to 2.56). The mean (±SD) maximum increase in serum creatinine level was 0.41±1.06 mg per deciliter (36.6±94.0 µmol per liter) in the BMES group and 0.41±1.02 mg per deciliter (36.1±90.0 µmol per liter) in the saline group, for a difference of 0.01 mg per deciliter (95% CI, -0.05 to 0.06) (0.5 µmol per liter [95% CI, -4.7 to 5.7]). The number of adverse and serious adverse events did not differ meaningfully between the groups. CONCLUSIONS: We found no evidence that the risk of death or acute kidney injury among critically ill adults in the ICU was lower with the use of BMES than with saline. (Funded by the National Health and Medical Research Council of Australia and the Health Research Council of New Zealand; PLUS ClinicalTrials.gov number, NCT02721654.).

Short communication: Effects of different blood buffers administered in electrolyte solution to grain-fed veal calves experiencing diarrhea.

Calf diarrhea can commonly lead to dehydration and metabolic acidosis due to the loss of fluid and electrolytes. The objective of this randomized clinical trial was to examine differences between treating male dairy calves experiencing diarrhea with either a basic bicarbonate electrolyte powder (BBP) composed of sodium bicarbonate (50.7 mmol/L); a mixed buffer powder (MBP) including sodium bicarbonate (33.8 mmol/L), sodium citrate (8.4 mmol/L), sodium acetate (6.3 mmol/L), and potassium citrate (1.9 mmol/L); or a liquid electrolyte (HAL) composed of sodium acetate (50.1 mmol/L). All 3 electrolyte solutions were standardized to provide 50 mmol/L blood buffers and a similarly strong ion difference (74.4, 74.9, and 82.6 mEq/L for BBP, MBP, and HAL, respectively). Holstein male calves (n = 80) were sourced from auction barns or local farms and delivered in 1 batch to the research facility. Calves were housed in individual pens and fed a 24% crude protein and 17% fat calf milk replacer (CMR) twice daily. Starter grain and water were offered ad libitum. Calves were randomly enrolled in 1 of the 3 treatments when experiencing either 2 consecutive days of a fecal score of 2 (runny, spreads easily) or 1 d with a fecal score of 3 (liquid devoid of solid material). Calves were blocked by the different enrollment criteria. The respective electrolyte solution was administered via esophageal tube 1 h after feeding CMR until the fecal score returned to 0 (normal consistency) or 1 (semiformed or pasty). Blood gas measurements were taken at 1, 8, and 24 h post the initial electrolyte feeding, and weight was measured at 1, 2, 7, 14, and 28 d postenrollment. Mixed repeated measure linear regression models were built to assess the effect that the electrolyte solutions had on the blood gas measurements and body weight. A total of 45 calves were enrolled in the trial with 14, 16, and 15 calves randomly assigned to the MBP, HAL, and BBP groups, respectively. As compared with BBP, MBP increased blood CO2 at 8 and 24 h, increased bicarbonate at 24 h, increased base excess at 8 and 24 h, and increased anion gap at 24 h. Calves in the BBP and HAL groups noted more severe eye recession when compared with the MBP group. Average daily gain did not differ between treatments at any time point. Although a severe dehydration challenge was not present, which should be considered a limitation of the study, MBP improved the acid-base status of calves compared with BBP, whereas HAL performed similarly to MBP.

Hypertonic saline buffered with sodium acetate for intracranial pressure management.

BACKGROUND: 3 % hypertonic saline (HS) is a hyperosmolar agent often used to treat elevated intracranial pressure (ICP). However, the resultant hyperchloremia is associated with adverse outcomes in certain patient populations. In this study, HS solution buffered with sodium acetate (HSwSA) is used as an alternative to standard 3 % formulations to reduce overall chloride exposure. Our objectives are to establish whether this alternative agent - with reduced chloride content - is similar to standard 3 % HS in maintaining hyperosmolarity and investigate its effects on hyperchloremia. METHODS: A retrospective chart review was conducted from August 1, 2014 to August 1, 2017 on patients receiving hypertonic therapies for ICP management. Patients were categorized into three groups, those that received: (1) 3 % HS for at least 72 h, (2) HSwSA for at least 72 h, or (3) were switched from 3 % HS within 72 h of initiating therapy to HSwSA for at least 72 h. RESULTS: The average increase in serum osmolality after 72 h of therapy was 21.1 moSm/kg for those only on 3 % HS and 20.3 mOsm/kg for those only on HSwSA. Serum chloride levels after 24 h decreased on average by 2.5 mEq/L after switching from 3% HS to HSwSA and stayed below baseline, whereas matched patients only receiving 3% HS on average had serum chloride levels increase 4.3 mEq/L after 24 h and continued to rise. CONCLUSIONS: Hyperchloremia has been associated with decreased renal perfusion, increasing the risk of acute kidney injury and hyperchloremic metabolic acidosis. Compared to standard 3% HS, our findings suggest an alternative hyperosmolar therapy with less chloride maintains similar hyperosmolarity while reducing overall chloride exposure.

SCFAs alleviated steatosis and inflammation in mice with NASH induced by MCD.

This study aimed to assess the effects of three major SCFAs (acetate, propionate, and butyrate) on NASH phenotype in mice. C57BL/6 mice were fed a methionine- and choline-deficient (MCD) diet and treated with sodium acetate, sodium propionate, or sodium butyrate during the 6-week feeding period. SCFA treatment significantly reduced serum levels of alanine aminotransferase and aspartate transaminase, the numbers of lipid droplets, and the levels of triglycerides and cholesterols in livers of the mice compared with control treatment. SCFAs also reduced MCD-induced hepatic aggregation of macrophages and proinflammatory responses. Among the three SCFAs, sodium acetate (NaA) revealed the best efficacy at alleviating MCD-induced hepatic steatosis and inflammation. Additionally, NaA increased AMP-activated protein kinase activation in the liver and induced the expression of fatty acid oxidation gene in both the liver and cultured hepatocytes. In vitro, NaA decreased MCD-mimicking media-induced proinflammatory responses in macrophages to a greater extent than in hepatocytes. These results indicated that NaA alleviates steatosis in a manner involving AMPK activation. Also, NaA alleviation of hepatic inflammation appears to be due to, in large part, suppression of macrophage proinflammatory activation. SCFAs may represent as a novel and viable approach for alleviating NASH.

0.9% saline versus Plasma-Lyte as initial fluid in children with diabetic ketoacidosis (SPinK trial): a double-blind randomized controlled trial.

BACKGROUND: Acute kidney injury (AKI) is an important complication encountered during the course of diabetic ketoacidosis (DKA). Plasma-Lyte with lower chloride concentration than saline has been shown to be associated with reduced incidence of AKI in adults with septic shock. No study has compared this in DKA. METHODS: This double-blind, parallel-arm, investigator-initiated, randomized controlled trial compared 0.9% saline with Plasma-Lyte-A as initial fluid in pediatric DKA. The study was done in a tertiary care, teaching, and referral hospital in India in children (> 1 month-12 years) with DKA as defined by ISPAD. Children with cerebral edema or known chronic kidney/liver disease or who had received pre-referral fluids and/or insulin were excluded. Sixty-six children were randomized to receive either Plasma-Lyte (n = 34) or 0.9% saline (n = 32). MAIN OUTCOMES: Primary outcome was incidence of new or progressive AKI, defined as a composite outcome of change in creatinine (defined by KDIGO), estimated creatinine clearance (defined by p-RIFLE), and NGAL levels. The secondary outcomes were resolution of AKI, time to resolution of DKA (pH > 7.3, bicarbonate> 15 mEq/L & normal sensorium), change in chloride, pH and bicarbonate levels, proportion of in-hospital all-cause mortality, need for renal replacement therapy (RRT), and length of ICU and hospital stay. RESULTS: Baseline characteristics were similar in both groups. The incidence of new or progressive AKI was similar in both [Plasma-Lyte 13 (38.2%) versus 0.9% saline 15 (46.9%); adjusted OR 1.22; 95% CI 0.43-3.43, p = 0.70]. The median (IQR) time to resolution of DKA in Plasma-Lyte-A and 0.9% saline were 14.5 (12 to 20) and 16 (8 to 20) h respectively. Time to resolution of AKI was similar in both [Plasma-Lyte 22.1 versus 0.9% saline 18.8 h (adjusted HR 1.72; 95% CI 0.83-3.57; p = 0.14)]. Length of hospital stay was also similar in both [Plasma-Lyte 9 (8 to 12) versus 0.9% saline 10 (8.25 to 11) days; p = 0.39]. CONCLUSIONS: The incidence of new or progressive AKI and resolution of AKI were similar in both groups. Plasma-Lyte-A was similar to 0.9% Saline in time to resolution of DKA, need for RRT, mortality, and lengths of PICU and hospital stay. TRIAL REGISTRATION: Clinical trial registry of India, CTRI/2018/05/014042 (ctri.nic.in) (Retrospectively registered).

Plasma-Lyte 148 vs. Hartmann's solution for cardiopulmonary bypass pump prime: a prospective double-blind randomized trial.

BACKGROUND: The mechanisms of acid-base changes during cardiopulmonary bypass (CPB) remain unclear. We tested the hypothesis that, when used as CPB pump prime solutions, Plasma-Lyte 148 (PL) and Hartmann's solution (HS) have differential mechanisms of action in their contribution to acid-base changes. METHODS: We performed a prospective, double-blind, randomized trial in adult patients undergoing elective cardiac surgery with CPB. Participants received a CPB prime solution of 2000 mL, with either PL or HS. The primary endpoint was the standard base excess (SBE) value measured at 60 minutes after full CPB flows (SBE60min). Secondary outcomes included changes in SBE, pH, chloride, sodium, lactate, gluconate, acetate, strong ion difference and strong ion gap at two (T2min), five (T5min), ten (T10min), thirty (T30min) and sixty (T60min) minutes on CPB. The primary outcome was measured using a two-tailed Welch's t-test. Repeated measures ANOVA was used to test for differences between time points. RESULTS: Twenty-five participants were randomized to PL and 25 to HS. Baseline characteristics, EURO and APACHE scores, biochemistry, hematology and volumes of cardioplegia were similar. Mean (SD) SBE at T60min was -1.3 (1.4) in the PL group and -0.1 (2.7) in the HS group; p=0.55. No significant differences in SBE between the groups was observed during the first 60 minutes (p=0.48). During CPB, there was hyperacetatemia and hypergluconatemia in the PL group and hyperlactatemia and hyperchloremia in the HS group. No significant difference between the groups in plasma bicarbonate levels and total weak acid levels were found. Complications and intensive care unit and hospital length of stays were similar. CONCLUSIONS: During CPB, PL and HS did not cause a significant metabolic acidosis. There was hyperacetatemia and hypergluconatemia with PL and hyperchloremia and hyperlactatemia with HS. These physiochemical effects appear clinically innocuous.

The Plasma-Lyte 148 v Saline (PLUS) study protocol: a multicentre, randomised controlled trial of the effect of intensive care fluid therapy on mortality.

BACKGROUND: 0.9% sodium chloride (saline) is the most commonly administered resuscitation fluid on a global basis but emerging evidence suggests that its high chloride content may have important adverse effects. OBJECTIVE: To describe the study protocol for the Plasma- Lyte 148 v Saline study, which will test the hypothesis that in critically ill adult patients the use of Plasma-Lyte 148 (a buffered crystalloid solution) for fluid therapy results in different 90-day all-cause mortality when compared with saline. DESIGN AND SETTING: We will conduct this multicentre, blinded, randomised controlled trial in approximately 50 intensive care units in Australia and New Zealand. We will randomly assign 8800 patients to either Plasma-Lyte 148 or saline for all resuscitation fluid, maintenance fluid and compatible drug dilution therapy while in the ICU for up to 90 days after randomisation. OUTCOME MEASURES: The primary outcome is 90-day all-cause mortality; secondary outcomes include mean and peak creatinine concentration, incidence of renal replacement therapy, incidence and duration of vasoactive drug treatment, duration of mechanical ventilation, ICU and hospital length of stay, and quality of life and health services use at 6 months. RESULTS AND CONCLUSIONS: The PLUS study will provide high-quality data on the comparative safety and efficacy of Plasma-Lyte 148 compared with saline for resuscitation and compatible crystalloid fluid therapy in critically ill adult patients.

A multicentre randomised controlled pilot study of fluid resuscitation with saline or Plasma-Lyte 148 in critically ill patients.

BACKGROUND: Normal saline (NS) is the most commonly used crystalloid solution worldwide but contains an excess of chloride and may cause metabolic acidosis and hyperchloraemia. Such abnormalities may be attenuated by the use of a balanced solution such as Plasma-Lyte 148 (PL-148). OBJECTIVE: To assess the feasibility, safety and biochemical and physiological effects of resuscitation with NS versus PL-148 in critically ill patients. DESIGN, SETTING AND PARTICIPANTS: An exploratory, multicentre, doubleblind, randomised controlled trial involving patients aged ≥ 18 years who were prescribed crystalloid fluid resuscitation by the treating clinician between 16 July and 22 October 2015, in three multidisciplinary intensive care units in Melbourne, Victoria, Australia. METHODS: Random allocation of NS or PL-148 was concealed, and all fluids were delivered in indistinguishable bags. INTERVENTION: NS or PL-148 was administered for all fluid resuscitation and for all subsequent crystalloid fluid therapy until Day 4 of ICU admission. The treating intensivist determined the rate and frequency of fluid administration. MAIN OUTCOME MEASURES: Primary outcome was daily base excess (BE). Relevant secondary outcomes included the incidence of acute kidney injury (AKI), change in serum creatinine and serum chloride levels, and mortality. RESULTS: Seventy patients were recruited, with 34 in the NS group and 33 in the PL-148 group available for analysis. Baseline characteristics of study patients were well balanced; the mean ages were 64 and 62 years, respectively, and nearly two-thirds of the patients in each group were men. The median Acute Physiology and Chronic Health Evaluation III scores were 64 for the NS group (interquartile range [IQR], 48-73) and 55 for the PL-148 group (IQR, 44-81). After treatment, there was no significant difference in the worst (most negative) median BE between the NS and PL-148 groups (-4 mEq/L [IQR, -7 to -2 mEq/L] v -3 mEq/L [IQR, -7 to 2 mEq/L]; P = 0.42). Chloride levels were significantly higher with NS therapy (median, 111 mmol/L [IQR, 108-116 mmol/L] v 108 mmol/L [IQR, 106-110 mmol/L]; P = 0.01). There was no significant difference in the incidence of AKI (P = 0.48), peak creatinine levels (P = 0.92) or ICU or hospital mortality between the two groups. CONCLUSIONS: In our exploratory, double-blind, randomised controlled trial, when compared with NS, PL-148 did not significantly increase BE values in critically ill patients requiring fluid resuscitation, but decreased peak chloride concentrations.

A randomized-controlled trial of high- or low-volume intravenous Plasma-Lyte(®) to prevent hypotension during sedation for colonoscopy.

PURPOSE: The purpose of this study was to compare the incidence of hypotension during sedation in adults presenting for elective colonoscopy and randomized to intravenous Plasma-Lyte 148(®) at either 2 mL·kg(-1) (low volume) or 20 mL·kg(-1) (high volume). METHODS: Patients aged ≥ 18 yr presenting for elective colonoscopy, with or without gastroscopy, after oral bowel preparation were randomized to receive the intervention immediately before the start of the procedure. Hypotension was defined as a ≥ 25% decrease in systolic blood pressure (SBP) from baseline during the procedure. Secondary outcomes included SBP < 90 mmHg, lowest SBP during sedation, duration of hypotension, use of vasopressors, postoperative outcomes, and cost. RESULTS: Seventy-five patients were randomly allocated to either the low-volume or high-volume group, respectively (total n = 150). The incidence of hypotension was similar in the two groups (59% vs 56%, respectively; odds ratio, 0.90; 95% confidence interval, 0.47 to 1.71; P = 0.74). The incidence of SBP < 90 mmHg, the lowest SBP during sedation, the duration of hypotension, the use of vasopressors, and postoperative outcomes were also similar in the two groups. CONCLUSIONS: This study does not support the routine use of 20 mL·kg(-1) of intravenous Plasma-Lyte 148 to prevent hypotension and other complications during sedation for elective colonoscopy in adult patients. Clinical Trials Registry (ANZCTR 12615001288516).

The effects of plasmalyte-148 vs. Hartmann's solution during major liver resection: a multicentre, double-blind, randomized controlled trial.

BACKGROUND: The acid-base, biochemical and hematological effects of crystalloid solutions have not been comprehensively evaluated in patients with liver resection. DESIGN: multicenter, prospective, double-blind randomized controlled trial investigating the biochemical effects of Hartmann's solution (HS) or Plasmalyte-148 (PL) in 60 patients undergoing major liver resection. PRIMARY OUTCOME: base excess immediately after surgery. SECONDARY OUTCOMES: changes in blood biochemistry and hematology. RESULTS: At completion of surgery, patients receiving HS had equivalent mean standard base excess (-1.7±2.2 vs. -0.9±2.3 meq/L; P=0.17) to those treated with PL. However, patients treated with HS were more hyperchloremic (difference 1.7 mmol/L, 95% CI: 0.2 to 3.2, P=0.03) and hyperlactatemic (difference 0.8 mmol/L, 95% CI: 0.2 to 1.3; P=0.01). In contrast, patients receiving PL had higher mean plasma magnesium levels and lower ionized calcium levels. There were no significant differences in pH, bicarbonate, albumin and phosphate levels. Immediately after surgery, mean PT and aPTT were significantly lower in the PL group. Intraoperatively, the median (IQR) blood loss in the PL group was 300 mL (200:413) vs. 500 mL (300:638) in the HS group (P=0.03). Correspondingly, the postoperative hemoglobin was higher in the PL group. Total complications were more frequent in the HS Group (56% vs. 20%, relative risk 2.8; 95% CI: 1.3 to 6.1; P=0.007). CONCLUSION: In liver resection patients, HS and PL led to similar base excess values but different post operative plasma biochemistry and hematology values. Understanding of these effects may help clinicians individualize fluid therapy in these patients.

A protocol for the 0.9% saline versus Plasma-Lyte 148 for intensive care fluid therapy (SPLIT) study.

BACKGROUND: 0.9% saline is the most commonly used intravenous (IV) fluid in the world. However, recent data raise the possibility that, compared with buffered crystalloid fluids such as Plasma-Lyte 148, the administration of 0.9% saline to intensive care unit patients might increase their risk of acute kidney injury (AKI). OBJECTIVE: To describe the protocol for the 0.9% Saline v Plasma-Lyte 148 for ICU Fluid Therapy (SPLIT) study. METHODS: This is a multicentre, cluster-randomised, double crossover feasibility study to be conducted in four New Zealand tertiary ICUs over a 28-week period and will enroll about 2300 participants. All ICU patients who need crystalloid IV fluid therapy (except those with established renal failure needing dialysis and those admitted to the ICU for palliative care) will be enrolled. Participating ICUs will be randomly assigned to 0.9% saline or Plasma-Lyte 148 as the routine crystalloid IV fluid, in a blinded fashion, in four alternating 7-week blocks. MAIN OUTCOME MEASURES: The primary outcome will be the proportion of patients who develop AKI in the ICU. Secondary outcomes will include the difference between the most recent serum creatinine level measured before study enrollment and the peak serum creatinine level in the ICU; use of renal replacement therapy; and ICU and in hospital mortality. All analyses will be conducted on an intention-to-treat basis. RESULTS AND CONCLUSION: The SPLIT study started on 1 April 2014 and will provide preliminary data on the comparative effectiveness of using 0.9% saline v Plasma- Lyte 148 as the routine IV fluid therapy in ICU patients.

Sodium acetate as a replacement for sodium bicarbonate in medical toxicology: a review.

Sodium bicarbonate is central to the treatment of many poisonings. When it was placed on the FDA drug shortage list in 2012, alternative treatment strategies to specific poisonings were considered. Many hospital pharmacies, poison centers, and medical toxicologists proposed sodium acetate as an adequate alternative, despite a paucity of data to support its use in medical toxicology. The intention of this review is to educate the clinician on the use of sodium acetate and to advise them on the potential adverse events when given in excess. We conducted a literature search focused on the pharmacology of sodium acetate, its use as a buffer in pathologic acidemia and dialysis baths, and potential adverse events associated with excess sodium acetate infusion. It appears safe to replace sodium bicarbonate infusion with sodium acetate on an equimolar basis. The metabolism of acetate, however, is more complex than bicarbonate. Future prospective studies will be needed to confirm the efficacy of sodium acetate in the treatment of the poisoned patient.

Randomized clinical trial of goal-directed fluid therapy within an enhanced recovery protocol for elective colectomy.

BACKGROUND: Goal-directed fluid therapy (GDFT) has been compared with liberal fluid administration in non-optimized perioperative settings. It is not known whether GDFT is of value within an enhanced recovery protocol incorporating fluid restriction. This study evaluated GDFT under these circumstances in patients undergoing elective colectomy. METHODS: Patients undergoing elective laparoscopic or open colectomy within an established enhanced recovery protocol (including fluid restriction) were randomized to GDFT or no GDFT. Bowel preparation was permitted for left colonic operations at the surgeon's discretion. Exclusion criteria included rectal tumours and stoma formation. The primary outcome was a patient-reported surgical recovery score (SRS). Secondary endpoints included clinical outcomes and physiological measures of recovery. RESULTS: Eighty-five patients were randomized, and there were 37 patients in each group for analysis. Nine patients in the GDFT and four in the fluid restriction group received oral bowel preparation for either anterior resection (12) or subtotal colectomy (1). Patients in the GDFT group received more colloid during surgery (mean 591 versus 297 ml; P = 0·012) and had superior cardiac indices (mean corrected flow time 374 versus 355 ms; P = 0·018). However, no differences were observed between the GDFT and fluid restriction groups with regard to surgical recovery (mean SRS after 7 days 47 versus 46 respectively; P = 0·853), other secondary outcomes (mean aldosterone/renin ratio 9 versus 8; P = 0·898), total postoperative fluid (median 3750 versus 2400 ml; P = 0·604), length of hospital stay (median 6 versus 5 days; P = 0·570) or number of patients with complications (26 versus 27; P = 1·000). CONCLUSION: GDFT did not provide clinical benefit in patients undergoing elective colectomy within a protocol incorporating fluid restriction. REGISTRATION NUMBER: NCT00911391 (http://www.clinicaltrials.gov).

Plasma-Lyte 148 vs 0.9% saline for fluid resuscitation in diabetic ketoacidosis.

PURPOSE: The purpose of the study was to determine the effects of Plasma-Lyte 148 (PL) vs 0.9% saline (NS) fluid resuscitation in diabetic ketoacidosis (DKA). METHODS: A multicenter retrospective analysis of adults admitted for DKA to the intensive care unit, who received almost exclusively PL or NS infusion up until 12 hours, was performed. RESULTS: Nine patients with PL and 14 patients with NS were studied. Median serum bicarbonate correction was higher in the PL vs NS groups at 4 to 6 hours (8.4 vs 1.7 mEq/L) and 6 to 12 hours (12.8 vs 6.2 mEq/L) from baseline (P < .05). Median standard base excess improved by 10.5 vs 4.2 mEq/L at 4 to 6 hours and by 16.0 vs 9.1 mEq/L at 6 to 12 hours in the PL and NS groups, respectively (P < .05). Chloride levels increased significantly in the NS vs PL groups over 24 hours. Potassium levels were lower at 6 to 12 hours in the PL group. Mean arterial blood pressure was higher at 2 to 4 hours in the PL group, whereas cumulative urine output was lower at 4 to 6 hours in the NS group. There were no differences in glycemic control or duration of intensive care unit stay. CONCLUSION: Patients with DKA resuscitated with PL instead of NS had faster initial resolution of metabolic acidosis and less hyperchloremia, with a transiently improved blood pressure profile and urine output.