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.

Clinical Efficacy and Safety of Sodium Thiosulfate in the Treatment of Uremic Pruritus: A Meta-Analysis of Randomized Controlled Trials

Uremic pruritus is a distressful complication of chronic kidney disease and results in impaired quality of life and higher mortality rates. Intravenous sodium thiosulfate has been reported to alleviate pruritus in hemodialysis patients. We performed a systematic review and meta-analysis to estimate the efficacy of intravenous sodium thiosulfate in patients with uremic pruritus. A systematic search of electronic databases up to June 2021 was conducted for randomized controlled trials that evaluated the clinical effects of sodium thiosulfate in the management of patients with uremic pruritus. Two reviewers selected eligible articles and evaluated the risk of bias; the results of pruritus assessment and uremic pruritus-related laboratory parameters in selected studies were analyzed. There are four trials published between 2018 and 2021, which include 222 participants. The sodium thiosulfate group displayed significant decrease in the pruritus score (standardized mean difference = −3.52, 95% confidence interval = −5.63 to −1.41, p = 0.001), without a significant increase in the adverse effects (risk ratio = 2.44, 95% confidence interval = 0.37 to 15.99, p = 0.35) compared to the control group. Administration of sodium thiosulfate is found to be a safe and efficacious complementary therapy in improving uremic pruritus in patients with chronic kidney disease.

The Treatment Results in Patients with Aluminum Phosphide Toxicity Admitted to Razi Hospital in Ahvaz

Introduction: Aluminum phosphide (ALP), locally known as "Rice Tablet", is a cheap and powerful pesticide used frequently to protect cereals. Cases of ALP toxicity have grown dramatically in recent decades by using it for suicide purposes. Treatment of ALP toxicity is largely supported by various remedies as there is no specific antidote. This study deals with the epidemiology of ALP toxicity in Khuzestan (Iran) and assesses the clinical and paraclinical manifestations, as well as the results of various treatments during the last 12 years. The study further examines the next suicidal intentions and subsequent complications of poisoning with ALP. Methodology: The records of all patients with ALP toxicity admitted to Razi Hospital in Ahvaz from 2006 to 2017 were reviewed within a retrospective study. Epidemiological and demographic information, clinical and paraclinical manifestations, and the results of various treatments were extracted. Data on the subsequent complications and the next suicidal intentions in those who have survived a suicide attempt were gathered and analyzed. Results: Of the 48 patients studied, 50% were male and the mean age was 29.33±10.45. Most of the toxicities were orally and with the intention of suicide in Ahvaz and Andimeshk. A total of 71.42% of the dead have been carried to this center. The majority of cases were reported from urban areas and in August and during summer. The most prevalent clinical signs were loss of consciousness, nausea, and vomiting. There were some differences in the experimental and EKG results. A meaningful correlation was observed between the administration and/or consumption of ranitidine, NAC, and intravenous sodium bicarbonate with treatment outcomes. Only one case of reattempt to suicide has been reported, and hematuria, ascites, and pleural effusion were widely visible in survivors. Conclusion: On-call counseling may decrease the rate of mortality in dispatching patients. Clinical and paraclinical manifestations can be useful in the diagnosis or prognosis. Patients' follow-up, actions to enhance public awareness, restrictions on the distribution of ALP, and availability of alternative substances can be helpful to diminish cases of ALP toxicity and/or death. Keywords: Aluminum phosphide (ALP), Rice tablets, Poisoning, Khuzestan

Severe metabolic acidosis and hyperkalemia after peptide receptor radionuclide therapy. A case report, review of the literature and proposed treatment algorithm

Peptide receptor radionuclide therapy (PRRT) has been increasingly used in the treatment of patients with well-differentiated neuroendocrine neoplasms (WD-NENs), but electrolyte abnormalities during prophylactic aminoacid (AA) infusion can complicate its administration. We describe a case of AA-induced acidosis and hyperkalemia associated with PRRT. We tailored an oral and intravenous sodium bicarbonate regimen for pre-emptive treatment prior to subsequent PRRT session, thereby preventing hospitalization. We provide a relevant review of the literature and our treatment algorithm, that can serve as a point of reference in treatment of this life-threatening complication of PRRT.

Therapeutic potential of mega-dose vitamin C to reverse organ dysfunction in sepsis and COVID-19

Sepsis causes multi-organ dysfunction and is a major cause of death in intensive care units, but there are no treatments that reverse the pathophysiological effects of sepsis. Vitamin C has antioxidant, anti-inflammatory, anticoagulant and immune modulatory actions, so is a potential treatment for sepsis. Recent clinical trials of high-doses of intravenous vitamin C (6-16 g/day) had variable effects. Since much higher doses are without side-effects in cancer and burns patients, we studied the effects of a mega-dose of intravenous sodium ascorbate (150 g/40 kg) in a clinically relevant ovine model of sepsis. This treatment dramatically improved the clinical state and over 3-7-h improved cardiovascular, pulmonary, hepatic and renal function and reduced body temperature. In a critically ill COVID-19 patient, intravenous sodium ascorbate (60 g) restored arterial pressure, improved renal function and increased arterial blood oxygen levels. Clinical trials are testing the effectiveness of mega-dose vitamin C in septic patients.

Therapeutic potential of mega-dose vitamin C to reverse organ dysfunction in sepsis and COVID-19

Sepsis causes multi-organ dysfunction and is a major cause of death in intensive care units, but there are no treatments that reverse the pathophysiological effects of sepsis. Vitamin C has antioxidant, anti-inflammatory, anticoagulant and immune modulatory actions, so is a potential treatment for sepsis. Recent clinical trials of high-doses of intravenous vitamin C (6-16 g/day) had variable effects. Since much higher doses are without side-effects in cancer and burns patients, we studied the effects of a mega-dose of intravenous sodium ascorbate (150 g/40 kg) in a clinically relevant ovine model of sepsis. This treatment dramatically improved the clinical state and over 3-7-h improved cardiovascular, pulmonary, hepatic and renal function and reduced body temperature. In a critically ill COVID-19 patient, intravenous sodium ascorbate (60 g) restored arterial pressure, improved renal function and increased arterial blood oxygen levels. Clinical trials are testing the effectiveness of mega-dose vitamin C in septic patients.

Sodium Bicarbonate in Different Critically Ill Conditions

Intravenous sodium bicarbonate is commonly used in several critically ill conditions for the management of acute acidemia independently of the etiology, and for the prevention of acute kidney injury, although this is still controversial from a physiologic point of view.

Use of intravenous sodium bicarbonate in neonatal intensive care units in Italy: a nationwide survey

Background Metabolic Acidosis (MA) is a disturbance of the acid-base balance that can occur in preterm and critically ill term neonates due to different etiologies. Intravenous sodium bicarbonate (SB) has been traditionally used to correct such unbalance, despite the lack of evidence about its safety and efficacy. In literature, reported undesirable effects of treatment with SB in neonates include worsening of intracellular acidosis, impairment of myocardial function, cerebral blood flow fluctuations and intracranial hemorrhage. A national survey was conducted by the Neonatal Pharmacotherapy Study Group of the Italian Society of Neonatology with the aim to assess and describe attitudes and practices concerning the use of SB, particularly for the treatment of MA in Italian NICUs. Methods A questionnaire regarding treatment of MA and SB prescription habits was sent to the directors of 120 Italian NICUs from June 2017 to March 2018. Results The survey response rate was 97.5% (117/120 centers). Findings showed that in 55% of the surveyed NICUs (64/117 units) it is common practice to correct MA with intravenous SB. On the other hand, the remaining 45% of the units try to solve the metabolic disturbances adopting different approaches (improving perfusion, adjusting ventilation parameters or increasing blood volume). Moreover, to prevent the occurrence of MA, 37.6% of the NICUs (44/117) include buffer salts (lactate, acetate or both) in parenteral nutrition prescriptions. SB is also used as a treatment for other conditions, mainly pathologies with bicarbonate loss and tubular acidosis (respectively in 53.8 and 32.5% of the NICUs). Conclusion This survey showed how SB is a commonly used treatment for MA in more than half of Italian NICUs, with indications and prescription criteria that significantly vary across centers. Based on current knowledge, it is reasonable to suggest that the management of neonatal MA should be firstly directed to identify the underlying disorders. Thus, the use of SB should be reserved only for selected cases, also considering the severity of SB adverse effects and the lack of evidence about its efficacy. Guidance for the management of MA is required to harmonize practices and reduce the use of potentially inappropriate and unsafe treatments.