Alchemist

[Alchemist]

Dear Naveed,

Below are my thoughts about sodium in Neonatal PN:

1-Premature neonates often have unstable electrolyte requirements. To the best of my knowledge there is no reference stating the ceiling doses of electrolytes in PN. 

2-Maintenance requirement of sodium 2-6 mmol/kg 

3-Adjustment of sodium in PN is based on patient assessment. Patient may require 8-12 mmol/kg of sodium as acetate or chloride.

4-It’s vitally important to identify underlying cause before increasing Sodium in PN. 

5-Factors that may increase sodium requirements include: Prematurity, Renal sodium loss from a high fractional excretion of sodium, Excessive water intake, Excessive maternal fluid intake during delivery. Diuretic therapy, especially loop diuretics. Acute tubular necrosis  (tubular sodium loss) and other causes of renal failure. Excess sodium loss: Diarrhea, Gastric, pleural, CSF)

6-Whenever possible the underlying cause should be treated, rather than just treating the serum sodium concentration.

Hope this will help.

[Alchemist]

Several articles have been written on cleaning HD areas. If you visit http://www.pppmag.com” and search for the term “cleaning. This search helps you out.

We are using 2% sodium hypochlorite solution., followed by sodium thiosulfate to inactivate the chlorine to keep it from corroding or pitting the stainless steel work surfaces, followed by sterile Isopropyl Alcohol 70%.

[Alchemist]

The FDA review you have included actually refers to BA resulting into gasping syndrome in doses > 99 mg/kg/day in neonates and low birth weight preterm infants:

“Benzyl Alcohol Toxicity

• Use preservative-free Heparin Sodium Injection in neonates and infants. The preservative benzyl alcohol has been associated with serious adverse events and death in pediatric patients. The “gasping syndrome” (characterized by central nervous system depression, metabolic acidosis, gasping respirations, and high levels of benzyl alcohol and its metabolites found in the blood and urine) has been associated with benzyl alcohol dosages >99 mg/kg/day in neonates and low-birth weight infants. Additional symptoms may include gradual neurological deterioration, seizures, intracranial hemorrhage, hematologic abnormalities, skin breakdown, hepatic and renal failure, hypotension, Bradycardia, and cardiovascular collapse.”

The statement about the amount that causes the toxicity is unknown as in subsequent section of the FDA’s review this is mentioned. However I would like to highlight the background of this problem. Back in the 80s, a number of neonatal fatalities were attributed to BA toxicity, however that was in a setting where routine line flushing with heparinized fluid that also contained a bacteriostatic and had BA in concentration of 9 mg/mL. I quote the CDC’s report in 1982:

“Review of the medical records of the affected infants resulted in estimates of daily intake of benzyl alcohol ranging from 99 to 405 mg/kg/day. Based on these reports, the FDA has recommended that intravascular flush solutions containing benzyl alcohol not be used for newborns and that diluents with this preservative not be used as medications for these infants.”

http://www.cdc.gov/mmwr/preview/mmwrhtml/00001109.htm

I think that this practice is not common now in the clinical setting. However you always weight the risk according to your setting.

[Alchemist]

Regarding your question about piperacillin/tazobactam BUD after reconstitution, first i think BUD is not the most accurate term to use we can say as its shelf life or stability after reconstitution as like Mariah demonstrated BUD is more related to microbial growth rather than the chemical and physical stability of the drug.

Best in this case i guess to get back to the leaflet of each specific product as based on each company test about their own product, even if general recommendations gave other extended time, it’s rather to use the product specific consideration when available

In the attachments you will find FDA specific leaflet for ZOSYN which states “ Discard unused portion after 24 hours if stored at room temperature (20°C to 25°C [68°F to 77°F]), or after 48 hours if stored at refrigerated temperature (2°C to 8°C [36°F to 46°F]).” Page 5 of the attachment.

There’s another package leaflet at https://www.medicines.org.uk/emc/files/pil.1267.pdf that is revised lately 1/2020 stating “Chemical and physical in-use stability has been demonstrated for up to 12 hours when stored in a refrigerator at 2-8°C, when reconstituted with one of the compatible solvents for reconstitution “ page 7 of the attachment from medicines.org.uk (emc).

Another source that mentioned after reconstitution stability is lexicomp.com which states “ Discard any unused portion after 24 hours if stored at 20°C to 25°C (68°F to 77°F) or after 48 hours if stored at 2°C to 8°C (36°F to 46°F). Do not freeze vials after reconstitution. Stability in D5W or NS has been demonstrated for up to 24 hours at room temperature and up to 1 week at refrigerated temperature. Stability in an ambulatory IV infusion pump has been demonstrated for a period of 12 hours at room temperature.”, you will find a screen shot attachment regarding lexicomp page.

https://mega.nz/file/CgBiVTyZ#EnGhRShNzSUUAE6A56L-QMo_JrAC8LwpaLCMg_vSCWM

https://mega.nz/file/i4BWXTjR#rKl-QvLcIss4Kr2Nwqs1tL0CE4HhWK2baOO6H5ZQk9w

Hope you find this useful,

[Alchemist]

Dear Naveed,

Kindly find this article regarding the effect of cirrhotic liver disease on drug metabolism through CYP system. This can give a general idea as chronic damage will have more profound effect than acute one unless the latter is a fulminant case.

Generally speaking, Dengue fever, by itself; necessitates supportive therapy rather than medications that require adjustment. For other medications that the patient may be already using like antihypertensives, antidiabetics and so on, I think that you can:-

1- Consider the specific drug monograph especially for extensively eliminated medications and adjust accordingly as mentioned earlier

2- Monitor clinical response of the patient and adjust accordingly, e.g BP, Glucose level,…

3- Avoid hepatotoxic medications and replace with safer ones

4- Consider alternatives for medications that are extensively eliminated hepatically, e.g Opiates, NSAIDs, Benzodiazepines….

To conclude, my opinion is that the effect of acute hepatic disease on CYP metabolism will depend on severity and duration (Chronic VS Acute) with probable lesser effect in case of mild short-term acute cases which may call for dose titration, starting with lower dose; with vigilant and clinically based judgment considering drug specific metabolism profile. This is evidenced by the referenced recommendations of no change in drug dosages in mild to moderate liver disease in many hepatically eliminated drugs.

Any further concerns are most welcomed.

My Best Regards,

[Alchemist]

Hello, get a new bag and start infusing again if there are a significant amount of crystals. I recommend getting a new bag since the mannitol is crystalizing = necessary drug that is now no longer available to give to the patient. Perhaps withdraw the amount already infused from the new bag before starting, or set your IV pump to only infuse the remainder that would be needed.

Many times to reduce chance of crystallization I will convert orders from 25% to 20% mannitol, but it can still happen.

Ensure you always infuse mannitol through a filter (usually a filter needle which is 5 micron in size is adequate) in case that happens.

[Alchemist]

I don’t have a definite evidence for your inquiry but I would recommend the maximum solubility option, in other words; choose maximum calcium and phosphate based on dextrose or Amino acid used whichever is higher. Below is my interpretation: –

1- Solubility of Calcium phosphate depends on the availability of soluble form of phosphate (monobasic phosphate) which tends to be available with increased acidity of TPN solution.

2- Referring to the equation of PH calculation in typical situation (excluding other factors such as inherent buffering capacity and dissociation constants): –

A) PH= – log [H⁺]

B) Assuming PH of (X) with the said volume (1000 ml) of the chosen solution (AA, D5W, D20W or D50W)

C) Assuming total volume of (3000ml), i.e (3) times the volume of the chosen acidic solution; then the PH would increase by the value of [- log (1/3) = 0.477].

3- The increase in PH would be lower than assumed in (C) as a part of the added solutions is usually acidic considering either amino acid or dextrose as additive with referral to their role as main determinants of the final PH as well as inherent buffering capacity.

Attached is a theoretical numerical example for the recommended allowed amounts of glycophos and calcium based on the final concentration of the said used components. Referring to the said example, kindly observe that using higher dextrose concentration would allow higher amounts of phosphate and calcium to be incorporated as well as lower volumes to be used.

Generally speaking, risk of precipitation with organic phosphate is lower than that with inorganic phosphate.

Again, this is a theoretical interpretation which I hope to be reviewed and assured as appropriate.

Hope this help with your query.

https://mega.nz/file/S5YRgIIC#zFZNxchQmAKT7QLbOc1QNPvw_lp2SYFe3LS6X-B_VYI

[Alchemist]

Thanks for your interesting inquiry.

Kindly find the below suggested reasons for favoring the use of lipids over carbohydrates and especially for premature infants:-

1- lipids typically provide energy in an amount of 2.6 times that of dextrose. Therefore providing energy from carbohydrates instead of lipids will cause an overwhelmig carbohydrate load. Here we come to your concern.

2- Dextrose = CO2, many premature infants already have ARDS! (Theoretically thinking)

3- Dextrose higher than 18 gm/kg tends to shift the metabolic process to lipogenesis.

4- Lipid intake is needed to prevent essential fatty acid deficiency.

[Alchemist]

The compounding of amiodarone oral solution from tablets generally involves adding methylcellulose or adding in a certain amount of 8.4% sodium bicarbonate (same as the injection) to balance the pH to around 7. This will likely solve the precipitation issues. You would have to add in enough to reach this balanced pH (testing with litmus paper or probe).

The PHYSICAL stability of these formulations are found in multiple studies as 90 days refrigerated. However the general USP 795 recommendations for compounded non-sterile aqueous formulations is limited to 14 days refrigerated, so set yours to match especially if giving to NICU patients. USP 795 accounts for the risks of MICROBIAL growth in making the BUD limit of 14 days even though the PHYSICAL stability can be longer.

Attached are compounding formulas for 5 different children’s hospitals that essentially say the same thing. Two do not say how much sodium bicarb to add but 2 others do, and it is about 4 mL with each three 200 mg tablets according to one formula, and 12 mL with each 5 tablets to another, so you could take an average of the two and work with that if you do not have any means to test pH.

https://mega.nz/file/2opmSLiA#6u8jcNrl8Ja7FlgrNeG_fCU8Ti_4G89ZD48ZTYDw_XU

If you have found the tablets to dissolve in simple syrup alone this could have a slightly different pH than what has been studied and may have shorter physical stability making it very hard to determine a uniform stability time for your batched product. Inspect the product each time you dispense to ensure it has not started to precipitate. I still think the physical stability would be longer than that USP 795 stability of 14 days so keep it at max 14 days refrigerated and you should be ok. Each of these formulas have the literature references you would be looking for.

Check the previously posted preparation here.

AMIODARONE SUSPENSION 40MG/ML

[Alchemist]

@naveed

Epleronone would be a good choice

[Alchemist]

Asking private Questions but totally confidential :
1- What’s exact problem do you face inn your intimate relation ship?
2-Since when it started? Sudden onset or Gradual?
3-Do you feel the mind is willing but the body is not?
4-Do you have a problem in sustaining erection?
5-Do you notice Morning Erection?
6-How do you feel inside your self?
———————————————–
Based on the rapid screening, If it occurs sudden onset so mostly it’s Psychological rather than medical cause….
Management :
1- Education and counselling about the problem
2- Counselling about the importance to be compliant on HF medications for survival improvement despite the fact that may be some medications may be implicated in Erectile dysfunction (Especially Beta blockerr ) with empathy and sympathy
3-We can selectively prescribe Nebivolol rather than any other Betablocker as it’s known to improve endothelial NO system
3-Prescription of PDi (Sildenafil or Taladafil) would be helpful
4-Correct other Modifiable risk factors for atherosclerosis (Like DM, HTN , Obesity, Hyperlipidemia, Smoking)
5-Check androgen levels to exclude secondary Hypogonadism associated with Cardiac patients and if low replacement would help after Consulting Andrologist.
6-involve Psychiatrist to assess the patient mood because depression also one of important causes of ED in such patients.

[Alchemist]

Here you go …

Liver Enzyme inducers and inhibitors – cytochome p450

HEPATIC ENZYME INHIBITORS 

SICKFACES.COM 
Sodium valproate 
Isoniazid 
Cimetidine 
Ketoconazole 
Fluconazole 
Alcohol..binge drinking 
Chloramphenicol 
Erythromycin 
Sulfonamides 
Ciprofloxacin 
Omeprazole 
Metronidazole 

HEPATIC ENZYME INDUCERS
  
GP PARCS 
Griseofulvin 
Phenytoin 
Phenobarbitone 
Alcohol..chronic use 
Rifampicin 
Carbamazepines 
Sulfonylureas

or… 

CRAP GPs

Carbemazepines 
Rifampicin 
Alcohol (chronic) 
Phenytoin 

Griseofulvin 
Phenobarbitone 
Sulphonylureas

[Alchemist]

Personally I have learned from the following PN references:

1. Parenteral & Enteral Nutrition by J. Rambeau

2. ASPEN Parenteral Nutrition Handbook by Ayers et al.,

3. Subscription of American Journal of Parenteral & Enteral Nutrition and Nutrition in Clinical Practice by ASPEN

4. Applied Therapeutics (Koda Kimble) & Pharmacotherapy (DiPiro) Chapters on Nutrition

My personal opinion: To learn PN, 70% of knowledge & Experience come from the mentor/preceptor and 30% from references. I strongly recommend the PGY-2 Nutrition Support residency

[Alchemist]

Hi there

Selection the type of the labels and the printing method is the key , as you have to make sure the labels quality and orienting method is not affected by sporicidal or IPA 70% which will be used to clean the ingredients before placed in the isolator without affecting the printing.

Using THERMAL PRINTERS and CHEMICAL RESISTANT LABELS FOR THERMAL TRANSFER PRINTERS will help.

Regards,

[Alchemist]

Yes, it should be done ISO 5 Laminar flow located in ISO 7 clean room

[Author]

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