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.

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.

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.

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.

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 acetate, gluconate and interleukin-6 profiles during and after cardiopulmonary bypass: a comparison of Plasma-Lyte 148 with a bicarbonate-balanced solution.

INTRODUCTION: As even small concentrations of acetate in the plasma result in pro-inflammatory and cardiotoxic effects, it has been removed from renal replacement fluids. However, Plasma-Lyte 148 (Plasma-Lyte), an electrolyte replacement solution containing acetate plus gluconate is a common circuit prime for cardio-pulmonary bypass (CPB). No published data exist on the peak plasma acetate and gluconate concentrations resulting from the use of Plasma-Lyte 148 during CPB. METHODS: Thirty adult patients were systematically allocated 1:1 to CPB prime with either bicarbonate-balanced fluid (24 mmol/L bicarbonate) or Plasma-Lyte 148. Arterial blood acetate, gluconate and interleukin-6 (IL-6) levels were measured immediately before CPB (T1), three minutes after CPB commencement (T2), immediately before CPB separation (T3), and four hours post separation (T4). RESULTS: Acetate concentrations (normal 0.04 to 0.07 mmol/L) became markedly elevated at T2, where the Plasma-Lyte group (median 3.69, range (2.46 to 8.55)) exceeded the bicarbonate group (0.16 (0.02 to 3.49), P < 0.0005). At T3, levels had declined but the differential pattern remained apparent (Plasma-Lyte 0.35 (0.00 to 1.84) versus bicarbonate 0.17 (0.00 to 0.81)). Normal circulating acetate concentrations were not restored until T4. Similar gluconate concentration profiles and inter-group differences were seen, with a slower T3 decay. IL-6 increased across CPB, peaking at T4, with no clear difference between groups. CONCLUSIONS: Use of acetate containing prime solutions result in supraphysiological plasma concentrations of acetate. The use of acetate-free prime fluid in CPB significantly reduced but did not eliminate large acetate surges in cardiac surgical patients. Complete elimination of acetate surges would require the use of acetate free bolus fluids and cardioplegia solutions. TRIAL REGISTRATION: Australia and New Zealand Clinical Trials Register (ANZCTR): ACTRN12610000267055.

Use of Walpole's solution for treatment of goats with urolithiasis: 25 cases (2001-2006).

OBJECTIVE: To determine results of ultrasound-guided cystocentesis and percutaneous infusion of Walpole's solution for treatment of male goats with urolithiasis. DESIGN: Retrospective case series. ANIMALS: 25 male goats with urolithiasis treated with Walpole's solution. PROCEDURES: Information obtained from the medical records included signalment, degree of urethral obstruction (partial vs complete), pertinent examination findings, concurrent illnesses, diet, other treatments administered, duration of hospitalization, whether the obstruction resolved, and outcome (ie, discharged vs euthanized). RESULTS: 14 (58%) animals had complete urethral obstruction, and 10 (42%) had partial obstruction (degree of urethral patency was not recorded in 1 animal). Walpole's solution was infused once in 18 (72%) animals, twice in 6 (24%) animals, and 3 times in 1 (4%) animal. The amount of Walpole's solution required to achieve the target urine pH of 4 to 5 ranged from 50 to 250 mL. In 20 (80%) goats, the urethral obstruction resolved, and the goat was discharged. The remaining 5 (20%) goats were euthanized because of unresolved urethral obstruction. Six of the 20 (30%) goats that were discharged were reexamined because of recurrence of urethral obstruction. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that ultrasound-guided cystocentesis in combination with percutaneous infusion of Walpole's solution may be a useful treatment in male goats with obstructive urolithiasis.

Deshidratación hipernatremica en recién nacido por sales de rehidratación oral reporte de un caso / Hypernatremic deshydration in newborn by salts of oral rehydration: a case report

La deshidratación hipernatremica se define como una concentración sérica de sodio mayor de 150 mEq/L, representa el 20 por ciento de las deshidrataciones y refleja un déficit de agua extracelular con relación al contenido corporal de sodio con edema cerebral, hemorragia intracraneal, hidrocefalia y gangrena. Los factores de riesgo para deshidratación hipernatrémica son: niños menores de un año por inmadures renal y aumento del líquido extracelular, fiebre que aumenta la pérdida de agua libre y, fundamentalmente el ingreso incrementado de solutos con relación al contenido de agua libre, producto de la reshidratación oral con soluciones con alto contenido de sodio, formulas mal preparadas o alimentación al pecho exclusiva en madres con una aporte insuficiente de líquidos. Se trata de recién nacido de 13 días de vida quien presenta clínica de deshidratación y acidosis por síndrome diarreico agudo con antecedente de mala administración de Sales de rehidratación oral por parte de la madre con dilución inadecuada hiperosmolar. Hallazgos paraclínico, Hipernatremia, Hiperkalemia, acidosis metabólica e hipoxemia. Tratamiento: corrección de acidosis con solución 75 y rehidratación en 48 horas con solución hipoosmolar 0.22 por ciento. Presentamos este caso por ser una de las causas más frecuentes de deshidratación hipernatrémicas en recién nacidos, es importante exponer la necesidad de educación a las madres para la adecuada preparación de las sales de rehidratación oral, como método eficaz de prevenir la deshidratación. Y en aquellos casos de presentarse tal complicación, los médicos debemos conocer la adecuada correlación de las misma a modo de evitar las complicaciones.