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).

Improving the safety of high-concentration potassium chloride injection.

Objectives: Serious adverse effects, including arrhythmia and cardiac arrest, result from rapid intravenous high concentration of potassium chloride (KCl). We aimed to eliminate prescription of undiluted KCl and encourage dilution of KCl to 400 mEq/L and 40 mEq/L in the intensive care units (ICUs) and general and outpatient departments, respectively. Methods: Before the first intervention, we collected data regarding high-concentration KCl and interviewed representatives of physicians prescribing high-concentration KCl. Based on the guidelines in other countries on safely used concentrations of KCl (400 mEq/L), we negotiated with physicians to dilute KCl below 400 mEq/L. In the first intervention, we made rules based on surveys above. In the second intervention, we revised the rules based on opinions from physicians and pharmacists and investigated the change in the number of prescriptions of KCl concentration in each department. Continuing efforts with the safety manager ensured compliance of the rules by physicians and nurses in all departments. Results: After the first and second interventions, prescriptions for undiluted KCl in ICUs and general wards were eliminated (median=0). Prescriptions for <400 mEq/L KCl increased to 110 (median) after the first intervention and to 137 (median) after the second. In the general ward, 7 months after the first intervention, prescriptions for <400 mEq/L KCl had not increased. Compliance with our rules was high, and more than 72% of physicians and nurses were aware of the rules. Conclusions: The rules for administration of high-dose KCl successfully eliminated prescription of undiluted KCl, which was maintained using two plan-do-study-act cycles. Our intervention process could be useful in countries where prediluted formulations are unavailable or where prescriptions are not matched and undiluted ampules are used.

Systematic review of preservation solutions for allografts for liver transplantation based on a network meta-analysis.

AIMS: The aim of this work was to determine the best preservation solutions for allografts for liver transplantation by quantitative network meta-analysis. METHODS: Global electronic databases including PubMed, EMBASE, and Cochrane Library were searched for relevant randomized controlled trials. Seven pieces of parametric data were extracted from included studies for pooled estimation. A consistency model was used for direct and indirect comparisons. The cumulative probability P value was utilized to rank the solutions. A node-splitting model was utilized for testing the consistency of final data. Quality of evidence was assessed using the GRADE (Grades of Recommendations Assessment, Development and Evaluation) system. RESULTS: Eleven 2-arm trials including 1319 patients and 5 different solutions were finally included. HTK (Histidine-tryptophan-ketoglutarate) solution exhibited the best efficacy for decreasing the primary dysfunction rate, biliary complications and ICU-stay time (probability P = 0.43, 0.45 and 0.58, respectively). Celsior solution significantly decreased the rate of rejection and early retransplantation (probability P = 0.73 and 0.38, respectively), and enhanced patient and graft survival (probability P = 0.90 and 0.98, respectively) more than did other solutions. Overall, the quality of evidence was rated high or moderate. CONCLUSIONS: We suggested that HTK solution may offer the best safety during the perioperative period. However, Celsior solution led to better graft tolerance and exhibited greater benefit for long-term outcomes. And our conclusions still need to be further validated.

UW is superior to Celsior and HTK in the protection of human liver endothelial cells against preservation injury.

Celsior solution (CS), a new preservation solution in thoracic organ transplantation, was evaluated for its efficacy in cold preservation of human liver endothelial cells (HLEC) and was compared to University of Wisconsin solution (UW) and histidine-tryptophan-ketoglutarate solution (HTK, Custodiol). HLEC cultures were preserved at 4 degrees C in CS, UW, and HTK, for 2, 6, 12, 24, and 48 hours, with 6 hours of reperfusion. Levels of lactate dehydrogenase (LDH), 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), and adenosine 5'-triphosphate (ATP) were measured after each interval of ischemia and the respective phase of reperfusion. Preservation injury of HLEC as measured by LDH release, intracellular ATP level, and MTT reduction were overall significantly (P > CS > HTK.

Impact of particulate contamination in crystalloid cardioplegic solutions: studies by scanning and transmission electron microscopy.

The amount of particulate matter present in Bretschneider's cardioplegic solution (HTK) was assessed by laser-mediated particle counting. Permissible levels of contaminant particles with a distribution of diameters between 0.2 and 20 microns were found. A significant further increase in the particle count was observed when the fluid was administered for clinical use, which resulted in the additional release of particles from, for example, the infusion kit, which included an in-line filter with pores of 270 microns. Filtration of the HTK solution by a terminal inline filter (0.2 micron) significantly reduced the number of particles. In order to determine the chemical composition and the potential hazards of the particulate material we used scanning electron microscopy in combination with energy dispersive X-ray analysis and transmission electron microscopy to examine specimens taken from heart tissue obtained from Göttinger minipigs after cardioplegia and from humans undergoing mitral valve replacement after cardioplegia and reperfusion. Particles of various diameters were found either to be plugging coronary capillaries, to be adherent to the endothelial layer, or to be engulfed by polymorphonuclear (PMN) granulocytes, which appeared to be activated. Some of the PMN granulocytes were apparent in the endothelial layer. It is recommended, therefore, that a terminal in-line filter (0.2 micron) should be routinely used.