454 SHORT REPORTS JULY 2013 – VOL. 33, NO. 4 PDI hypomagnesemia. A higher frequency of hypertonic dialysate use was also involved in the development of hypomagnesemia. DISCLOSURES This work was supported by the National Basic Research Program of China (Grant No. 2011CB504005) and the Key Clinical Discipline Program of the Ministry of Health, China (Grant No. [2010] 439). Hongjian Ye 1,2† Xiaodan Zhang 1,2† Qunying Guo 1,2 Naya Huang 1,2 Haiping Mao 1,2 Xueqing Yu 1,2 Xiao Yang 1,2 * Department of Nephrology 1 The First Affiliated Hospital Sun Yat-sen University Key Laboratory of Nephrology 2 Ministry of Health Guangzhou, China *email: [email protected]† These authors contributed equally to the present work. REFERENCES 1. Agus ZS. Hypomagnesemia. J Am Soc Nephrol 1999; 10:1616–22. 2. Ejaz AA, McShane AP, Gandhi VC, Leehey DJ, Ing TS. Hypomagnesemia in continuous ambulatory peritoneal dialysis patients dialyzed with a low-magnesium perito- neal dialysis solution. Perit Dial Int 1995; 15:61–4. 3. Fried L, Bernardini J, Piraino B. Charlson comorbidity index as a predictor of outcomes in incident peritoneal dialysis patients. Am J Kidney Dis 2001; 37:337–42. 4. Cho MS, Lee KS, Lee YK, Ma SK, Ko JH, Kim SW, et al. Re- lationship between the serum parathyroid hormone and magnesium levels in continuous ambulatory peritoneal dialysis (CAPD) patients using low-magnesium peritoneal dialysate. Korean J Intern Med 2002; 17:114–21. 5. Avram MM, Mittman N, Bonomini L, Chattopadhyay J, Fein P. Markers for survival in dialysis: a seven-year prospective study. Am J Kidney Dis 1995; 26:209–19. 6. Soucie JM, McClellan WM. Early death in dialysis patients: risk factors and impact on incidence and mortality rates. J Am Soc Nephrol 1996; 7:2169–75. 7. Clinical practice guidelines for nutrition in chronic renal failure. K/DOQI, National Kidney Foundation. Am J Kidney Dis 2000; 35(Suppl 2):S1–140.[Erratum in: Am J Kidney Dis 2001; 38:917] 8. Uribarri J. Phosphorus homeostasis in normal health and in chronic kidney disease patients with special em- phasis on dietary phosphorus intake. Semin Dial 2007; 20:295–301. 9. Caddell JL, Goddard DR. Studies in protein–calorie malnu- trition. I. Chemical evidence for magnesium deficiency. N Engl J Med 1967; 276:533–5. 10. Rosen EU, Campbell PG, Moosa GM. Hypomagnesemia and magnesium therapy in protein–calorie malnutrition. J Pediatr 1970; 77:709–14. 11. Shah GM, Winer RL, Cutler RE, Arieff AI, Goodman WG, LacherJW, et al. Effects of a magnesium-free dialysate on magnesium metabolism during continuous ambulatory peritoneal dialysis. Am J Kidney Dis 1987; 10:268–75. 12. Katopodis KP, Koliousi EL, Andrikos EK, Pappas MV, Elisaf MS, Siamopoulos KC. Magnesium homeostasis in patients undergoing continuous ambulatory peritoneal dialysis: role of the dialysate magnesium concentration. Artif Organs 2003; 27:853–7. 13. Takahashi S, Okada K, Yanai M. Magnesium and parathyroid hormone changes to magnesium-free dialysate in continu- ous ambulatory peritoneal dialysis patients. Perit Dial Int 1994; 14:75–8. 14. Hutchison AJ, Merchant M, Boulton HF, Hinchcliffe R, Gokal R. Calcium and magnesium mass transfer in peri- toneal dialysis patients using 1.25 mmol/L calcium, 0.25 mmol/L magnesium dialysis fluid. Perit Dial Int 1993; 13:219–23. 15. Tzamaloukas AH. Avoiding the use of hypertonic dex- trose dialysate in peritoneal dialysis. Semin Dial 2000; 13:156–9. doi:10.3747/pdi.2012.00164 Ultrasound-Guided CAPD Catheter Insertion Methods commonly used for the insertion of peritone- al dialysis (PD) catheters are the surgical, laparoscopic, peritoneoscopic, and blind techniques. Blind insertion techniques include the Seldinger technique, the trochar method, and fluoroscopic guidance. Even though these techniques have evolved, most catheters are still being placed by a surgical technique. A recent report showed that only 2.3% of all catheter placements and 1% of lap- aroscopic insertions are performed by nephrologists (1). The involvement of other specialties and the associated need for interdepartmental coordination results in delays because of factors such as non-availability of a procedure room and the precedence of other surgical procedures and interventions over PD catheter placement. This single copy is for your personal, non-commercial use only. For permission to reprint multiple copies or to order presentation-ready copies for distribution, contact Multimed Inc. at [email protected]. at ARIZONA HEALTH SCIENCES LIBRARY on May 30, 2015 http://www.pdiconnect.com/ Downloaded from
Transcript
454
SHORT REPORTS july 2013 – Vol. 33, No. 4 PDI
hypomagnesemia. A higher frequency of hypertonic dialysate use was also involved in the development of hypomagnesemia.
DISCLOSURES
This work was supported by the National Basic Research Program of China (Grant No. 2011CB504005) and the Key Clinical Discipline Program of the Ministry of Health, China (Grant No. [2010] 439).
Hongjian Ye1,2† Xiaodan Zhang1,2†
Qunying Guo1,2 Naya Huang1,2
Haiping Mao1,2 Xueqing Yu1,2 Xiao Yang1,2*
Department of Nephrology1 The First Affiliated Hospital
Sun Yat-sen University Key Laboratory of Nephrology2
†These authors contributed equally to the present work.
REFERENCES
1. Agus ZS. Hypomagnesemia. j Am Soc Nephrol 1999; 10:1616–22.
2. Ejaz AA, McShane AP, Gandhi VC, Leehey DJ, Ing TS. Hypomagnesemia in continuous ambulatory peritoneal dialysis patients dialyzed with a low-magnesium perito-neal dialysis solution. Perit Dial Int 1995; 15:61–4.
3. Fried L, Bernardini J, Piraino B. Charlson comorbidity index as a predictor of outcomes in incident peritoneal dialysis patients. Am j Kidney Dis 2001; 37:337–42.
4. Cho MS, Lee KS, Lee YK, Ma SK, Ko JH, Kim SW, et al. Re-lationship between the serum parathyroid hormone and magnesium levels in continuous ambulatory peritoneal dialysis (CAPD) patients using low-magnesium peritoneal dialysate. Korean j Intern Med 2002; 17:114–21.
5. Avram MM, Mittman N, Bonomini L, Chattopadhyay J, Fein P. Markers for survival in dialysis: a seven-year prospective study. Am j Kidney Dis 1995; 26:209–19.
6. Soucie JM, McClellan WM. Early death in dialysis patients: risk factors and impact on incidence and mortality rates. j Am Soc Nephrol 1996; 7:2169–75.
7. Clinical practice guidelines for nutrition in chronic renal
failure. K/DOQI, National Kidney Foundation. Am j Kidney Dis 2000; 35(Suppl 2):S1–140.[Erratum in: Am j Kidney Dis 2001; 38:917]
8. Uribarri J. Phosphorus homeostasis in normal health and in chronic kidney disease patients with special em-phasis on dietary phosphorus intake. Semin Dial 2007; 20:295–301.
9. Caddell JL, Goddard DR. Studies in protein–calorie malnu-trition. I. Chemical evidence for magnesium deficiency. N Engl j Med 1967; 276:533–5.
10. Rosen EU, Campbell PG, Moosa GM. Hypomagnesemia and magnesium therapy in protein–calorie malnutrition. j Pediatr 1970; 77:709–14.
11. Shah GM, Winer RL, Cutler RE, Arieff AI, Goodman WG, LacherJW, et al. Effects of a magnesium-free dialysate on magnesium metabolism during continuous ambulatory peritoneal dialysis. Am j Kidney Dis 1987; 10:268–75.
12. Katopodis KP, Koliousi EL, Andrikos EK, Pappas MV, Elisaf MS, Siamopoulos KC. Magnesium homeostasis in patients undergoing continuous ambulatory peritoneal dialysis: role of the dialysate magnesium concentration. Artif organs 2003; 27:853–7.
13. Takahashi S, Okada K, Yanai M. Magnesium and parathyroid hormone changes to magnesium-free dialysate in continu-ous ambulatory peritoneal dialysis patients. Perit Dial Int 1994; 14:75–8.
14. Hutchison AJ, Merchant M, Boulton HF, Hinchcliffe R, Gokal R. Calcium and magnesium mass transfer in peri-toneal dialysis patients using 1.25 mmol/L calcium, 0.25 mmol/L magnesium dialysis fluid. Perit Dial Int 1993; 13:219–23.
15. Tzamaloukas AH. Avoiding the use of hypertonic dex-trose dialysate in peritoneal dialysis. Semin Dial 2000; 13:156–9.
doi:10.3747/pdi.2012.00164
Ultrasound-Guided CApD Catheter Insertion
Methods commonly used for the insertion of peritone-al dialysis (PD) catheters are the surgical, laparoscopic, peritoneoscopic, and blind techniques. Blind insertion techniques include the Seldinger technique, the trochar method, and fluoroscopic guidance. Even though these techniques have evolved, most catheters are still being placed by a surgical technique. A recent report showed that only 2.3% of all catheter placements and 1% of lap-aroscopic insertions are performed by nephrologists (1). The involvement of other specialties and the associated need for interdepartmental coordination results in delays because of factors such as non-availability of a procedure room and the precedence of other surgical procedures and interventions over PD catheter placement.
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Ultrasound guidance (USG) has been used to insert peritoneal catheters for palliation of malignant ascites (2). Contrast provided by the peritoneal fluid provides better visualization of the intraperitoneal structures and bowel loops (3). Maya (4) first described a fluoroscopic technique using additional USG to localize the epigastric artery and to observe the intraperitoneal entry of the introducer needle. That procedure provided additional safety by avoiding injury to the epigastric artery and related bleeding.
Developing countries have poor infrastructure, which limits the dissemination of PD as an alternative renal replacement therapy. We set out to use USG as the only guidance to balance the safety of a guided procedure with the risks of a blind procedure. Here, we describe the method we used.
METHODS
Patients choosing to use continuous ambulatory PD (CAPD) and not having any contraindications for PD cath-eter insertion were selected after informed consent was obtained. Premedication with 1 g cefazolin was given 30 minutes before the procedure. Patients allergic to peni-cillin were given 500 mg vancomycin. Conscious sedation was given with intravenous midazolam and ketamine.
Grayscale ultrasonography of the abdominal wall was performed on the side where the insertion was planned to determine the thickest portion of the rectus abdominis muscle for implantation of the inner cuff and to ensure that no underlying bowel loops were present in that location. Color Doppler sonography was used to visualize the epigastric artery, and the puncture site was kept at least 2 – 3cm away from the artery. All catheters used were 62-cm Tenckhoff catheters with two cuffs, pro-vided in a commercial kit (Quinton Curl Cath Peritoneal Catheter kit: Covidien, Mansfield, MA, USA). The posi-tion of the deep cuff and the exit site were determined and marked.
The entry site was then infiltrated with 10 mL 2% ligno-caine, and the 18-gauge introducer needle (provided in the catheter kit) was inserted at an angle of 45 degrees, directed toward the pelvis under USG [Figure 1(A)]. The tip was positioned just under the peritoneum, avoiding underlying bowel loops.
One liter of PD fluid was then instilled into the peri-toneal cavity through the introducer needle. Free flow of the fluid was confirmed by demonstration of localized turbulence on Doppler USG [Figure 1(B)]. The presence of fluid in the pelvis and the separation of bowel loops was noted. A 1-mm J guidewire (provided in the catheter kit) was then inserted through the introducer needle, and
with the peritoneal fluid providing contrast, the guide-wire position was visualized in the pelvis [Figure 1(C)].
The introducer needle was then removed, and a 3-cm vertical incision was made at the insertion site. Subcutaneous tissue was dissected with sharp and blunt dissection to expose the anterior rectus sheath. A 0.5-cm transverse incision was made on the anterior rectus sheath, and a pocket big enough to accommodate the deep cuff was made in the rectus muscle. A purse-string suture was then applied around the rectus sheath using 1-0 nylon and was left without knotting.
The peel-apart sheath, together with the dilator (16F Pull-Apart Sheath/Dilator: Covidien) was threaded over the guidewire directed toward the pelvis. The guidewire and the dilator were then removed, and the PD catheter was inserted through the sheath into the peritoneal cav-ity. The deep cuff was advanced into the rectus muscle by peeling away the sheath. The position of the catheter coil in the pelvis was checked using grayscale ultrasonogra-phy [Figure 1(D,E)]. The 1-0 nylon suture was then tight-ened over the deep cuff, and fluid drainage was checked before the knot was tightened [Figure 1(F)].
The catheter was then placed in the subcutaneous tunnel created using the tunneling stylet (provided in the catheter kit) and was brought out at the exit site (made by a 0.5-cm stab incision). Free flow of the PD fluid was confirmed, and the catheter position in the pelvis was rechecked by USG. The subcutaneous tissue over the catheter was closed in layers using absorbable sutures (1-0 Vicryl: Ethicon, Somerville, NJ, USA), and the skin was closed with 1-0 silk sutures. The titanium adapter and connecting segment were then connected to the catheter, and free outflow of the instilled fluid was rechecked. The remaining 1 L of PD fluid was then instilled into the peritoneal cavity, and free inflow was again confirmed.
Finally, all fluid was drained and measured to ensure that the drained fluid totalled to at least 1800 mL. The connecting segment and the titanium adapter, together with the exposed portion of the catheter were covered with gauze, and a transparent dressing was applied.
Erect and supine radiographs of the abdomen were taken immediately post-procedure to check the posi-tion of the catheter and to rule out bowel perforation. The patient was instructed to avoid heavy lifting and excessive straining. Laxatives were also given to prevent constipation and straining at stools. The transparent dressing was checked daily for soakage and infection, and was changed on day 4, when small-volume (300 – 500 mL) flushing was initiated. The volume of the fluid flushes and the duration of the fluid dwells were gradually increased to achieve the desired volume and duration by day 10.
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Over a period of 6 months from January 2012 to June 2012, we inserted 21 PD catheters. No immediate procedure-related complications occurred, including bowel perforation or bleeding.
One patient had a previous abdominal wall hernia repair, and a surgical option was contraindicated. Because of multiple access failures and an urgent need for dialysis, a percutaneous insertion was attempted for this patient. On insertion of the guidewire on the left side, USG showed the wire coiled in the left hypochondrium because of adhesions in the lef t paracolic region (which was visualized because of the instilled fluid). We changed the site of insertion to the right side, and after demonstrating the presence of the guidewire in the pelvis, we inserted the cath-eter, which could also be demonstrated in the pelvis. This patient did not experience any procedure-related complications, and PD was initiated without any problems on day 4.
Dialysis was able to be initiated in 20 patients (95.23%) starting on post-procedure day 4, and full-volume exchanges were achieved by 10.23 ± 0.53 days in these 20 patients. Only 1 patient (4.76%) developed pericatheter leakage, and after a rest of 4 days, full-volume exchanges were achieved by post-procedure
day 15. Only 1 episode of peritonitis occurred, on day 24 in a patient with end-stage renal disease related to systemic lupus erythematosus, which was adequately treated. Catheter position was rechecked on the day 30 by erect radiography of the abdomen, and no catheter malposition was documented.
DISCUSSION
Good access to the pelvic peritoneum for placing the CAPD catheter is the most important aspect of PD. Direct visualization of the abdominal cavity using a laparoscopic approach has yielded results comparable to those using the open surgical technique, with the advantage of being able to perform additional procedures such as adhesiolysis (5). But both of those procedures require greater sophistication, including an operating theater and general anesthesia. Although modifications such as peritoneal helium insufflation (6) have been used to avoid the need for general anesthesia, the role of the nephrologist in conducting these procedures is restricted to just a few centers with good training in interventional nephrology.
The Seldinger technique is a blind procedure, and it has an inherent risk of complications such as bowel perforation and bleeding. Bowel perforation, the most dreaded early complication after PD catheter insertion,
Figure 1 — (A) Using the ultrasound probe to direct the introducer needle. (B) Doppler ultrasonography shows a localized dis-turbance just under the peritoneum, because of the flow of peritoneal dialysis fluid into the peritoneal cavity. Deeper vessels can also be delineated. (C) The guidewire is seen in the pelvis, (D) followed by visualization of the catheter coil (black arrows) in the pelvis. (E) Catheter coil seen in another patient. (F) Anterior rectus sheath being closed over the deep cuff by applying a purse-string suture.
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has been reported in 1% of patients (5). This complica-tion usually occurs during the entry to the abdominal cavity or when the straightening stylet is advanced to the pelvis. Fluoroscopy has been used with comparable efficacy, especially by intervention radiologists, to ensure safe entry into the abdominal cavity and correct placement of the PD catheter in the pelvis (4).
Nonsurgical techniques using fluoroscopy have also shown advantages such as decreased procedure time and a very short time to CAPD initiation. Banli et al. (7) were able to initiate CAPD by day 6 after catheter insertion. Only 4.8% patients in their study had early pericatheter leak-age, and none experienced bowel perforation. An Indian study also showed that blind PD catheter insertions by nephrologists resulted in shorter time to initiation of CAPD (4.6 ± 2.4 days vs 6.31 ± 2.68 days), shorter duration of hospital stay, and a cost reduction of 50% (8).
Insertion of the PD catheter using the Seldinger technique results in outcomes that are similar to those with the open surgical and laparoscopic methods. But the inherent bias of most of the studies toward selec-tion of patients that have a more favorable safety profile for the Seldinger method (blind or fluoroscopy guided) has been highlighted in an editorial by Crabtree (9). Voss et al. (10), in a recently published randomized trial without that bias, compared fluoroscopy-assisted catheter insertion with laparoscopic catheter insertion. Those authors concluded that radiologic insertion is a clinically non-inferior and cost-effective alternative to surgical laparoscopic insertion. The long-term catheter survival rate was also higher in the radiologic insertion group in the study.
For percutaneous PD catheter insertion, fluoroscopy guidance is the only alternative method (short of a blind procedure) commonly used by intervention radiologists and nephrologists. But this facility is not available in most centers in the developing world. Involvement of the nephrologist in catheter insertion has been seen to lead to an increase of 22% – 32% in patients on CAPD; numbers decline when surgeons take over (11).
Initiation of CAPD can be accelerated by percutaneous methods that result in a shorter time to insertion, shorter time to initiation of PD, and comparable safety (12). Our method of using USG alone might make things simpler. The initial results have been encouraging. Short of the “blind” procedure, our technique can be used to “look into” the abdomen, reducing potential complications.
The limitations of our study are the small number of patients and their lower average body mass index of 22.13 ± 4.28 kg/m2. Thus, more experience with our USG procedure, especially in patients with a larger body mass index, is needed for further validation.
DISCLOSURES
The authors have no f inancial conflicts interest to declare.
5. Peppelenbosch A, van Kuijk WHM, Bouvy ND, van der Sande FM, Tordoir JHM. Peritoneal dialysis catheter placement technique and complications. NDT Plus 2008; 1(Suppl 4):iv23–8.
6. Crabtree JH, Fishman A. A laparoscopic approach under local anesthesia for peritoneal dialysis access. Perit Dial Int 2000; 20:757–65.
7. Banli O, Altun H, Oztemel A. Early start of CAPD with the Seldinger technique. Perit Dial Int 2005; 25:556–9.
8. Sampathkumar K, Mahaldar AR, Sooraj YS, Ramkrishnan M, Ajeshkumar, Ravichandran R. Percutaneous CAPD catheter insertion by a nephrologist versus surgical placement: a comparative study. Indian j Nephrol 2008; 18:5–8.
9. Crabtree JH. Fluoroscopic placement of peritoneal dialysis catheters: a harvest of the low-hanging fruits. Perit Dial Int 2008; 28:134–7.
10. Voss D, Hawkins S, Poole G, Marshall M. Radiological ver-sus surgical implantation of first catheter for peritoneal dialysis: a randomized non-inferiority trial. Nephrol Dial Transplant 2012; 27:4196–204.
11. Asif A, Pflederer TA, Vieira CF, Diego J, Roth D, Agar-wal A. Does catheter insertion by nephrologists improve
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peritoneal dialysis utilization? A multicenter analysis. Semin Dial 2005; 18:157–60.
12. Li PK, Chow KM. Importance of peritoneal dialysis cath-eter insertion by nephrologists: practice makes perfect. Nephrol Dial Transplant 2009; 24:3274–6.
doi:10.3747/pdi.2012.00206
effect of Glucose Concentration on the Stability of Daptomycin in
peritoneal Solutions
Daptomycin is a cyclic lipopeptide with rapid concen-tration-dependent bactericidal activity against almost all gram-positive pathogens (1). Intraperitoneal daptomy-cin administration in 1.5% and 2.5% glucose solutions has been effective in treating vancomycin-resistant Staphylococcus or Enterococcus peritonitis in peritoneal dialysis (PD) patients without a relapse or repeated peri-tonitis subsequently developing (2–7).
Daptomycin has been reported to degrade in 5% glu-cose solutions at a rate of 15% – 20% per 24 hours at room temperature (8). The saline concentration of PD solution can also have a significant impact on daptomycin stability (8). As previously reported, daptomycin is stable for 4 hours in a solution of 5% glucose in water, but for only 2.5 hours in a solution of 5% glucose in 0.45% saline at room temperature.
Little is known about stability of daptomycin in PD solution. The stability of daptomycin has recently been studied in 3 PD solutions respectively containing 1.36% glucose, icodextrin, and 1.1% amino acids (9), and dap-tomycin has been found to be stable in 1.36% glucose solution for at least 24 hours and in 1.1% amino-acid solution for more than 168 hours at 25°C. In both cases, the stability of daptomycin declines by more than 10% after 6 hours at 37°C.
The objective of the present work was to study the dependence of daptomycin stability on the glucose concentration in glucose PD solutions held in poly-vinylchloride containers at 25°C and 37°C. The chemical stability of daptomycin was also evaluated in icodextrin PD solution.
METHODS
Daptomycin (Cubicin: Novartis, Basel, Switzerland) was obtained as dry powder. The drug was resuspended in 10 mL sterile distilled water and stored at 4°C until use. Three different commercially available solutions for PD were tested: Physioneal 35 (1.36% glucose, 2.0 L bags, 7.5 pH for the mixed solution), Physioneal 35
(2.27% glucose, 2.0 L bags, 7.5 pH for the mixed solu-tion), and Extraneal (2.0 L bags, 5.5 pH) (all solutions: Baxter Healthcare Corporation, Deerfield, IL, USA). One daptomycin concentration was tested in three different bags of each PD solution. After removal of the overwrap from each solution bag, daptomycin was injected through the medication port into the glucose or icodextrin com-partment to obtain a final daptomycin concentration of 20 mg/L in each solution bag. The bags were inverted several times to ensure proper mixing and were stored at two temperatures (25°C and 37°C) in a climatic test system (Vötsch Industrietechnik, Balingen, Germany) held at 60% relative humidity. Samples were withdrawn from the stored bags either at 0, 1, 2, 4, and 6 hours after addition of the daptomycin (bags held at 37°C) or at 0, 8, and 24 hours after addition of the daptomycin (bags held at 25°C).
In addition, daptomycin stability was evaluated at ambient temperature and in the same concentration in two other intravenous solutions containing glucose and no other excipients: Glucosada Grifols 5% (Grifols, Barcelona, Spain) and Viaflo Glucosa 10% (Baxter Healthcare Corporation). Samples were withdrawn from these bags at 0, 0.5, 6, and 24 hours after addition of the daptomycin.
Daptomycin concentrations were measured using high-performance liquid chromatography with ultravio-let detection. The chromatographic system consisted of an Agilent 1200 SL pump, an autosampler, and a pho-todiode array detector. Chromatographic separations were achieved using a Gemini reverse-phase C18 column (150×4.6 mm, 5 μm: Phenomenex, Torrance, CA, USA) and a Gemini C18 guard column with the same package. Reagents for all assays met high-performance liquid chromatography grade. Standard working solutions were prepared from daptomycin stock solutions by serial dilu-tion to yield final concentrations of 1, 2.5, 10, 25, 50, 100, and 500 μg/mL. The (within-day) precision of the method was determined at four concentration levels (1, 3, 60, 300 μg/mL) to represent the low, medium, and high ranges of the calibration curve. Correlation coef-ficients (r) were better than 0.995 for the calibration curves. The assay was reproducible, with a between-day coefficient of variation of 12.98%.
The average and standard deviation of three bags were calculated at each sample time. For each analysis, the last time point at which drug concentrations exceeded 90% of baseline were used to denote stability.
RESULTS
All solutions were clear in appearance, and no color change or precipitation was observed throughout the
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