Metabolic Acidosis

Hyperchloremic metabolic acidosis was rather common with infusion of older TPN solutions because they contained protein hydrolysates and certain synthetic amino acids (lysine, arginine, and histidine) that were infused in hydrochloride form. In newer TPN preparations, arginine and histidine are available as free base and lysine as lysine acetate. Thus, the incidence of metabolic acidosis is greatly reduced.

Metabolic acidosis, when present, is mostly related to the presence of amino acids.

TPN solutions contain cationic (lysine, arginine, and histidine), anionic (aspartate and glutamate), and sulfur-containing (methionine, cysteine, and cystine) amino acids. Cationic amino acids contain nitrogen in their side chains, and when metabolized, they generate H⁺ at the rate of 1 mol per 1 mol of amino acid. Metabolism of sulfur-containing amino acids yields 2 mol of H⁺ (from sulfuric acid) per 1 mol of amino acid. Aspartate and glutamate have carboxylic (COO⁻) groups in their side chain, and when metabolized, they consume H⁺ with resultant formation of HCO₃ ⁻. Thus, these amino acids reduce acid load (H⁺ load) to the body. H⁺ that are produced from cationic and sulfur-containing amino acids are generally excreted as net acid excretion in the urine. If the patient has renal dysfunction, these H⁺ are retained, causing high anion gap metabolic acidosis. Management of this acid-base disorder involves NaHCO₃ and renal replacement therapy in patients with renal dysfunction.

Occasionally, hyperchloremic metabolic acidosis develops due to high Cl⁻ content in TPN solution. This will improve with lowering of Cl⁻ and increasing acetate in TPN solution. In patients with diarrhea and renal tubular acidosis, TPN may exacerbate hyperchloremic metabolic acidosis, and appropriate management of these disorders will correct this acid-base disorder.

Patients who are severely deficient in thiamine develop lactic acidosis despite TPN, which includes vitamins. This is related partly to the presence of high glucose in TPN solutions that demands thiamine for pyruvate dehydrogenase activity and partly loss of thiamine in the urine due to hyperosmolality-induced osmotic diuresis. Although it is a rare occurrence, monitoring thiamine levels may be necessary in some patients. Also, biotin deficiency has been reported to cause lactic acidosis. Replacement of both thiamine and biotin to maintain normal levels prevents the development of lactic acidosis.

Hypophosphatemia is common in patients on TPN despite its inclusion in these solutions. The reason for hypophosphatemia is cellular shift caused by glucose and amino acid-induced insulin secretion. In insulin-resistant diabetic subjects, insulin growth factor-1 transports phosphate into the cell. Hypophosphatemia decreases net acid excretion with resultant retention of H⁺ and development of metabolic acidosis.

Metabolic Alkalosis

Metabolic alkalosis is frequently seen in patients on TPN. Both the underlying disease processes requiring nasogastric suction, duodenal obstruction causing vomiting, and excess acetate infusions can increase serum HCO₃ ⁻ level with resultant metabolic alkalosis. Also, osmotic diuresis-induced volume depletion can raise serum HCO₃ ⁻ level and causes metabolic alkalosis. Dialysis patients on TPN develop post-dialysis metabolic alkalosis due to bicarbonate-containing dialysis solutions.

Respiratory Acidosis

TPN solutions contain glucose (carbohydrate), fatty acids (fats), and amino acids (protein). Respiratory quotient (RQ) is calculated for these nutrients to evaluate the basal metabolic rate of these nutrients. RQ is calculated from ratio of CO₂ production to O₂ consumption by the body. The RQ values for carbohydrates, fats, and proteins are 1.0, 0.7, and 0.8, respectively. When RQ value exceeds 1.0 for high carbohydrate intake, CO₂ production is high. In TPN, glucose content is usually high; as a result, the production of CO₂ is high. Patients with normal lung function can eliminate this excess CO₂, and CO₂ balance is maintained. If patients have impaired lung function (COPD or other diseases), they cannot eliminate this excess CO₂. As a result they retain CO₂ and develop respiratory acidosis. TPN-induced hypercapnia has been known for a long time. In addition to hypercapnia, infusion of large quantities of glucose was found to increase O₂ consumption, energy expenditure, tidal volume, and respiratory rate.

One of the earliest studies reported acute respiratory failure in three patients on ventilator support within 12 h following administration of high carbohydrate load.

Both CO₂ production and RQ increased with the development of respiratory acidosis. In one patient, pCO₂ increased from 43 to 93 mmHg, and pH fell from 7.40 to 7.25 within 24 h after increasing caloric intake from 1500 to 2500 kcal/day. Thus, high carbohydrate (glucose) load in TPN can cause respiratory acidosis in patients with impaired lung function.

Herve et al. [1] studied gas exchange and arterial blood gases in six patients with chronic respiratory failure, who were ventilated at low (6 L/min) and high (10 L/min) minute ventilation during three randomized nutritional regimens: (1) control (255 kcal/day); (2) glucose TPN (2550 kcal/day); and (3) lipid TPN (3000 kcal/day). At both levels of ventilation, TPN solutions increased CO₂ production and arterial pCO₂ when compared to controls. At low minute ventilation, both CO₂ production and hypercapnia were much less in those on lipid TPN than those on glucose TPN. These investigators suggest that the risk of TPN-induced hypercapnia is lower, if minute ventilation is increased before the start of TPN.

In summary, TPN induces respiratory acidosis in patients with impaired respiratory function, and weaning these patients from ventilators is difficult if they are on high glucose TPN feedings. Weaning is less difficult if they are on lipid TPN feedings or low caloric intake from carbohydrates.

Respiratory Alkalosis

Primary respiratory alkalosis has not been reported in patients with impaired lung function who are on TPN. It should be, however, noted that high glucose and amino acids in TPN may stimulate respiratory rate and lower serum HCO₃ ⁻ concentration.

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