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.

Use of the extracorporeal detoxification methods for methotrexate elimination

The article considers a clinical case of a 12-year-old child with osteosarcoma of the left tibia, T1N0M0G3, treated with high-dose methotrexate 12 g/m2. As a result of delayed elimination of methotrexate, the patient developed acute liver failure. The ALT level increased to 4790 U/L, AST — to 4320 U/L, which indicates life-threatening acute liver damage. There was no coagulopathy, significant increase in bilirubin, and hepatic encephalopathy. The timely use of efferent therapy allowed avoiding the complete course of acute liver failure. The patient received intravenous hydration therapy and urine alkalinization with 3000 ml/m2/day of 5% glucose in combination with 20 μmol NaHCO3/L and 20 μmol KCl/L. The urine output was more than 600 ml/m2/6 hours. Additionally, antidote therapy with calcium folinate was administered. In this case, we used continuous venous-venous hemodiafiltration using Prismaflex. After the first session, which lasted for 78 hours, there was a re-increase in serum methotrexate concentration and ALT, AST levels, which indicates a large volume of distribution of methotrexate and the need for long-term extracorporeal therapy. Therefore, the second session of continuous venous-venous hemodiafiltration was provided. After the second session, there was no re-increase in methotrexate level in the blood and the transaminases and total bilirubin returned to normal levels. Additionally, the patient was tested for homocysteine levels for hyperhomocysteinemia, as well as 4 genes that also determine the predisposition to hyperhomocysteinemia — methylenetetrahydrofolate reductase gene MTHFR C677T, A1298C, methionine synthase MTRR, and MTR. The presence of elevated levels of homocysteine, as well as heterozygosity of these genes, indicate a slow excretion of methotrexate or a complete delay in its excretion. Our patient presented the negative results of these tests. Conclusions. This clinical case indicates the effectiveness of continuous venous-venous hemodiafiltration in combination with intravenous hydration, urine alkalinization, and antidote therapy in the treatment of hepatotoxicity of high-dose methotrexate on the background of delayed excretion.

651 Prevention of contrast induced nephropathy with urine alkalinization: the final results of the TEATE study

Aims Contrast-induced acute kidney injury (CI-AKI) after coronary angiography and percutaneous interventions (PCI) impacts on hospitalization duration and mortality. Pre-procedural hydration is the sole strategy currently recommended for preventing CI-AKI. The role of sodium bicarbonate (SB) although attractive, since urine alkalinization suppresses the production of reactive oxygen species, is still controversial, and the optimal dosing to attain adequate urine alkalinization is still undefined. The PrevenTion of contrast-inducEd nephropathy with urine alkalinization (TEATE) study was a prospective 3-centre 3-arm single-blind randomized controlled trial testing the hypothesis that adequate urine alkalinization is associated with CI-AKI prevention. Secondary endpoints were the efficacy of SB vs. saline in achieving adequate urine alkalinization and reducing the incidence of CI-AKI compared with saline. Methods and results Patients candidate to coronary angiography and/or PCI with moderate-to-severe chronic kidney disease [eGFR of 15–60 ml/min/1.73 m2, by the Modification of Diet in Renal Disease Study equation (MDRD)] were randomly assigned to saline hydration (control), oral SB or i.v. SB. The study protocol was registered (ClinicalTrials.gov NCT02980003). We evaluated urinary pH at the time of hospitalization, immediately before coronary angiography and 24–48 h after angiography. According to urine pH immediately before the procedure, patients were divided in two groups above or below a pH cut-off of 6. We enrolled a total of 241 patients: 81 were randomly assigned to the control group, 82 to i.v. SB and 78 to oral SB. Patients achieving a urinary pH > 6 before angiography had a lower incidence of CI-AKI (46%) than patients with urinary pH ≤ 6 (54%) [OR = 0.48 (95% CI: 0.25–0.9), P = 0.023]. The number of patients with urine pH > 6 was higher in both the i.v. (71%) and the oral SB (65%) groups compared to the hydration-only group (44%, P = 0.004). We found however no difference in the incidence of CI-AKI in the three treatment arms (20% in hydration alone, 21% in oral SB group and 22% in i.v. SB group) (P = 0.94). Subgroup analyses according to basal urine pH and eGFR ranges failed to identify statistically significant differences in the development of CI-AKI according to treatment allocation. Conclusions Urinary pH before the administration of contrast medium is an inverse correlate of CI-AKI incidence, and SB is superior to hydration alone in achieving urinary alkalinization. Since, however, SB did not reduce the incidence of CI-AKI, we conclude that urinary pH is a marker and not a mediator of CI-AKI.

Evaluation of medical treatment in Iranian children with nephrolithiasis

Introduction: Nephrolithiasis has been increasingly recognized in recent years. Urine metabolic abnormality is the main cause of renal stone in children. Therefore, identification and medical treatment of metabolic abnormalities have been suggested as an alternative approach to surgical treatments. Objectives: This study was performed to evaluate the therapeutic effect of urine alkalinization and metabolic management in children with renal stone. Patients and Methods: A total of 300 children (from 408 renal clinics) with nephrolithiasis were enrolled in this study. All of them were treated by supportive managements, including urine alkalinization and specific medical treatment of underlying metabolic abnormality. Improvement was defined as stone resolution, stone passage or decrease of stone dimension. Results: Mean age at diagnosis was 28.7 ± 2.6 months (1-150 months). About 78.8% of patients had metabolic abnormality, of which, hypercalciuria (51.7%) and hypocitraturia (33.4%) were the most common causes, respectively. Resolution of renal stone occurred in 89.7% of patients after one year follow up, more in children less than 5 years (P=0.003), and stones smaller than 5 mm (P<0.001). However, 87.5% of large stones (5-12 mm) improved by medical treatment. Conclusion: Pharmacologic treatment is recommended in young children with small nephrolithiasis. Pharmacologic treatment also suggested as a primary intervention in children with uncomplicated large renal stones, and prior to invasive surgical management.

Evaluation of an Oral Sodium Bicarbonate Protocol for High-Dose Methotrexate Urine Alkalinization

Purpose: Intravenous (IV) sodium bicarbonate is considered standard therapy for high-dose methotrexate (HDMTX) urine alkalinization. Due to a national IV sodium bicarbonate shortage, an oral (PO) sodium bicarbonate protocol was implemented by Alberta Health Services (AHS) for HDMTX urine alkalinization. This study aims to evaluate the efficacy and safety of the PO sodium bicarbonate protocol compared to IV sodium bicarbonate for HDMTX urine alkalinization. Methods: A retrospective chart review of adult patients who received HDMTX (>500 mg/m2) with sodium bicarbonate for urine alkalinization at 4 hospitals in Alberta was conducted. Patients who received IV sodium bicarbonate between January-June 2017 and PO sodium bicarbonate between July-December 2017 were compared for the primary outcome of time to methotrexate clearance. Results: A total of 84 and 78 HDMTX cycles were included in the IV and PO cohorts, respectively. No difference in time to methotrexate clearance was seen between the IV and PO cohorts, 91.6 (± 35.4) hours and 95.2 (± 44) hours respectively; p=0.5. The proportion of HDMTX cycles that experienced a >25% increase in serum creatinine was not statistically significant, IV protocol 12% and PO protocol 5%; p=0.13. Nausea and emesis occurred more frequently in the PO cohort than the IV cohort, though rarely resulted in refused doses or change to alternate sodium bicarbonate formulations.Conclusions: The results of this study indicate that the AHS PO sodium bicarbonate protocol was no different in time to methotrexate clearance or rates of increased serum creatinine when compared to IV sodium bicarbonate.

Rhabdomyolysis After the Use of Percussion Massage Gun: A Case Report

Objective Percussion massage guns are commonly used by professional athletes and nonathletes worldwide for warmup and physical recovery; however, there are no published clinical or evidence-based reports on percussion guns regarding their benefits, indications, contraindications, and even side effects. The purpose of this case report is to describe the first case of rhabdomyolysis as a severe and potentially life-threatening illness following use of a percussion gun. Methods (Case Description) A young Chinese woman with untreated iron deficiency anemia presented with fatigue and pain in her thigh muscles for 3 days and tea-colored urine for 1 day, after cycling and subsequently receiving percussion gun treatment by her coach for the purpose of massage and relaxing tired muscles. Muscle tenderness and multiple hematomas were found on her thighs, and her urinalysis indicated hemoglobinuria. Her serum creatine kinase was reported as “undetectably high,” a hallmark of serious muscle damage leading to a diagnosis of severe rhabdomyolysis. Aggressive intravenous fluid resuscitation, urine alkalinization via intravenous alkaline solution, assessment of urine output, and maintenance of electrolyte balance were administered during hospitalization. Results The patient’s clinical presentation gradually improved with the decline of creatine kinase, and she recovered well during follow-up. Conclusion A case of severe rhabdomyolysis after percussion massage should alert caregivers, sports professionals, and the public to suspect and recognize the potentially serious adverse effects of percussion guns and to ensure that percussion massage guns be used appropriately and safely in rehabilitation therapy, especially in individuals with an underlying disease or condition. Research is needed to examine the benefits, indications, contraindications, and adverse reactions of percussion guns.

Rhabdomyolysis in a Civil Aviation Pilot

BACKGROUND: Rhabdomyolysis is a potentially fatal disease caused by trauma, infections, and toxins. Rhabdomyolysis has not been reported in Chinese civil aircrew, but in our case report a male civil copilot contracted rhabdomyolysis after excessive exercise, showing potential for morbidity in pilots.CASE REPORT: After excessive exercise, a 29-yr-old male civil aviation copilot complained of serious myalgia and weakness in lower limb muscles and gross hematuria, whose values of alanine transaminase (ALT), aspartate transaminase (AST), myohemoglobin (Mb), creatine kinase (CK), CK-MB, lactate dehydrogenase (LDH), and -hydroxybutyrate dehydrogenase (-HBDH) were conspicuously increased. Magnetic resonance imaging showed abnormal signal intensities in the lower limbs. The patient was diagnosed with rhabdomyolysis. He was treated with hydration and urine alkalinization. When his condition was stabilized, the patient was discharged. After remaining asymptomatic for 3 mo and getting documentation of normalized lab results, he was granted a first-class medical certificate and returned to work.DISCUSSION: This was the first case of rhabdomyolysis reported in Chinese civil aircrew. Excessive exercise in an overweight pilot may induce rhabdomyolysis. This condition can be controlled and cured by early and effective treatment. Rhabdomyolysis could occur in a population suffering from overweight, obesity, or hyperlipidemia. This case fits in with several other cases of military pilots exercising excessively. The progression could lead to acute kidney injury without prompt and effective intervention. And common symptoms like muscular weakness or myalgia may induce sudden in-flight incapacitation, so early medical intervention should be adopted. Moreover, recurrence of rhabdomyolysis should be considered when resuming flying duties.Liu X, Meng X, Zhang C, Chen J, Li P, Wu X, Fan H. Rhabdomyolysis in a civil aviation pilot. Aerosp Med Hum Res. 2020; 91(11):901903.

Oral sodium bicarbonate protocol for high-dose methotrexate urine alkalinization: A pediatric experience

Introduction Methotrexate (MTX) is a cytotoxic antimetabolite. Intravenous (IV) hydration and urine alkalinization with sodium bicarbonate (NaHCO3) can mitigate nephrotoxicity associated with high-dose MTX (HDMTX, doses ≥500 mg/m2). A shortage of IV NaHCO3 in 2017 prompted Alberta Children’s Hospital (ACH) and Stollery Children’s Hospital (SCH) to adopt an alternative protocol including oral NaHCO3 and IV hydration with Lactated Ringer’s (LR). Methods A retrospective chart review was conducted for ACH and SCH inpatients who received HDMTX between January and December 2017. The primary outcome was the proportion of cycles with delayed HDMTX clearance within the IV and oral cohorts. Secondary outcomes include NaHCO3 administered until clearance, NaHCO3 required to reach pH ≥7, time to reach pH ≥7, incidence of pH <7, time to clearance, and time to discharge. Adverse effects associated with delayed clearance or NaHCO3 administration were also reported. Results 112 MTX cycles were included, 50 and 62 from the IV and oral cohorts, respectively. Clearance delays beyond protocol expectations occurred in 10 cycles (8.9%), 5 from each cohort ( p = 0.72). Differences between cohorts were not statistically significant, except the amounts of NaHCO3 required until clearance (383 vs. 277 mmol/m2, p = 0.005) and to reach pH ≥7 (52 vs. 40 mmol/m2, p = 0.004) were lower in the oral cohort. Incidences of adverse effects were not different. Conclusions Oral NaHCO3 with LR is a feasible alternative for urine alkalinization. The total dose of NaHCO3 utilized was lower in the oral cohort, with no additional delays in clearance.