Heather Blois

[Heather Blois]

Dear Naveed,

Just after drafting this response, I noticed Alchemist and Christian’s brilliant responses. I eco them below, maybe in a bit different words, I guess no harm of the repeat.

2 – 6 is the maintenance listed in most of references and guidelines. However depending on level of prematurity, hydration status and oliguric versus polyuric phases seen due to prematurity and  renal impairment/recovery, you might need more or less.

Initially right after birth, preterm infants have translucent skin that contributes to dehydration. Those who are extremely premature, might require review to their sodium and fluid status every 6 hrs, this  can result into increasing the fluid intake in response to hypernatremia. Thus the first day PN is almost sodium free, with probably very small amount of sodium (1 mmol/kg) as sodium glycerol phosphate.

This is also to account for the fact that we still give sodium chloride in the form of saline or ½ saline flushes at times of line insertion, to keep arterial lines patent and to flush IV medications. Thus ½ saline is preferred and small flush volumes should be targeted. This might help control the iatrogenic hypernatremia and hyperchloremia early in life.

Neonates who go through renal impairment become oliguric and develop 3^rd spacing. During this phase they are hyponatremic, and you manage that by just giving the maintenance, while restricting the fluid intake in response to the increase in the oedema weight and sodium readings, as well as clinical findings of overload.

When they recover from the renal impairment phase, they start passing a lot of urine, and a lot of sodium with that, they might as well be responding to diuretics initiated during the oedema phase. During that time it might be helpful to respond to low sodium supplementations as much as needed. Calculation of deficiencies gives an idea of how much is needed.

Other instances when the needs are high is when there are stoma losses, as well as sodium losing congenital diarrhoeal diseases.

Now back to how much in PN. Mostly we just supplement the needed daily supplement of 2 – 6 mmol/kg/day, further corrections done outside PN is the optimal, and we can do that when the Total fluid intake allow given that we do not compromise nutrition for that. If you will need a lot of fluid to give side drips, or when there is extreme fluid restriction, correcting in the PN is unavoidable.

Regards,

[Heather Blois]

We are using the  preservative-free Heparin Sodium Injection in neonates and infants (Porcine source) . The cause is that the “preservative benzyl alcohol” has been associated with serious adverse events and death in pediatric patients. The minimum amount of benzyl alcohol at which toxicity may occur is not known. Premature and low-birth weight infants may be more likely to develop toxicity!

From my experience at 3 different tertiary hospitals in Riyadh, we all use the preservative free heparin in neonatal/ pediatric TPN.

[Heather Blois]

Thank you for your inquiry which I hope to be able to address.

Hepatic adjustment is usually based on manufacturer recommendations from clinical studies unlike that of Creatinine Clearance for evaluating kidney function.

To make it easy for understanding, let’s refer to the basics of renal drug adjustment: –

        1-      Creatinine, a metabolite of muscle creatine; is solely excreted by kidney

        2-      Renal elimination of creatinine is mainly determined by GFR

        3-      Using Creatinine Clearance can be a reliable measure for kidney function as it relies mainly on one variable        which is GFR

        4-      The clearance of renally excreted drugs is also dependent mainly on GFR rather than other renal ways like secretion

        5-      Thus, using CrCl can be a simple and effective way of adjusting the doses of renally excreted drugs in renally    impaired patients

On the other hand, hepatic impairment can affect all stages of drug pharmacokinetics: –

1-      Absorption: – Through affecting GI function

2-      Distribution: – Through affecting albumin production and associated protein binding of some drugs

3-      Metabolism: – Impairment of CYP system

4-      Excretion: – Through affecting bile production. It may also affect kidney function.

These factors are complex, when compared to the single GFR factor associated with kidney failure.

Thus, it’s advised to include hepatic impairment during the clinical studies for medications to get a more reliable idea about the required adjustment and relate it to the numerical value obtained from classification systems (Child – Pugh, MELD,….) .

To conclude: –

       1-      Severity of liver disease is usually estimated through Child-Pugh classification which incorporates many factors compromised by hepatic failure. Other equations are also developed, yet; Child – Pugh is still the most frequently used.

       2-      Drug adjustment in hepatic disease is complex and requires more investigation during the clinical studies in order to get better insight about the recommended doses. Always refer to the specific drug monograph.

       3-      Generally speaking, high extraction ratio (removed extensively by liver) drugs can be roughly reduced by 50% while those with low extraction ratio can be reduced by 25%. In both cases, close monitoring of effects and side effects is advised.

        4-      Attached: –

1. A)Guidance for industry by FDA for including hepatic impairment as a dosing guideline.
2. B)Review article about Pharmacokinetics and dosage adjustment in patients with hepatic dysfunction.

I hope that this answers your query.

[Heather Blois]

In addition to the great thoughts of Alchemist and Nawal, mines are shown below… In summary life is about BALANCE and the balance theory necessitates calories diversion as explained below. The concept is the same among Adults and Pediatrics.

1. The source of provided calories to meet Energy Expenditure must be diversed between Dextrose and Lipid as the oxidative capacity of both dextrose and fat in Pediatrics (and in adults) is limited. Therefore, around 60% of calories must be provided as Carbohydrate (not more than 70% and not less than 20%). In adult, the maximum oxidative capacity is 5mg/kg/min and if you do a simple calculation, this accounts to 60% of total needed calories. The minimal dextrose that needs to be provided to an adult  patient even with Glucose intolerance is 120-150g per day; this accounts to 2 mg/kg/min or 25% of total calories. Extra dextrose calories above 5mg/kg/min or 60-70% of total calories leads to Liponeogenesis (de novo lipogenesis) thus huge production of CO2 (RQ = VO2/CO2 more than 8).

2. Lipid is much safer source of calories than carbohydrate if the clearance capacity is assured. As said by Alchemist, lipid produces lower CO2 upon oxidation (Respiratory Quotient is 0.7 compared to 1 with Dextrose). Lipid does not cause electrolytes derangement like dextrose as fat stimulates little insulin release. However, Dextrose is much more efficient source of calories as it stimulates more Insulin that is important for the shift of intracellular ions; therefore synthesis of a balanced cell. Extra lipid beyond 1.5g/kg/day or 60% of total calories lead to Lipogenesis (Fatty liver disease)

3. Minimal dose of lipid to prevent Essential Fatty Acid deficiency is 10% of total calories or around 0.25g/kg/d. We make it 40% to support Dextrose in the formation of cell membrane that is phospholipid in nature and to replete the wasted calories from the catabolic/metabolic process.

[Heather Blois]

we use alteplase to maintain catheter patency. However, I found out an old study with regards of steptokinase use for the same issue, please find it attached with wellness.

Reconstituted Solutions: Streptase reconstituted with 5 mL of saline

(Sodium Chloride Injection USP, 0.9%) or dextrose (Dextrose Injection

USP, 5%) is stable for 24 hours at room temperature (15 to 30°C) and

refrigeration (2 to 4°C).

Hope that helps

[Author]

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