Intravenous Nutrient Solutions
Dextrose usually makes up ~ 70% of the caloric intake, but as it is not a potent metabolic fuel it has to be hyperosmolar, and thus infused through large central veins. Amino acid solutions come in several varieties, but in general they contain ~ 50% essential amino acids and ~ 50% non-essential/semi-essential amino acids. The nitrogen in essential amino acids is recycled to form non-essential AAs and thus the BUN does not increase as much, which is why solutions designed for renal failure use a higher fraction of essential AAs. Similarly, hypercatabolic patients and liver failure patients use branched chain amino acid-rich formulas. There is no data to suggest that any of these special formulas improve outcomes [Nutr Clin Pract 9: 28, 1994]. Glutamine, has been shown to reduce atrophic changes in bowel epithelium [J Surg Res 48: 383, 1990] but the clinical value of this amino acid is unknown at present and not effective enterally [Crit Care Med 33: 2501, 2005]
Lipid emulsions are long-chain fatty acids derived from safflower or soybean oil and generally rich in linoleic acid. They are available in 10 and 20% strengths, are roughly isotonic and thus can be infused peripherally (or centrally if piggybacked to the dextrose solutions). Triglycerides take 8-10 hours to clear, thus the patient’s plasma will often look milky. Lipids are oxidation-prone and have been shown to promote oxidant injury [Nutr Clin Pract 8: 55, 1993], thus Marino believes that one should consider restricting their use to the minimum required (he does not provide any citations to support this, however) – in order to prevent essential fatty acid deficiency, 4% of calories must be supplied by linoleic acid [Ann Surg 193: 3014, 1981]
Electrolytes (Na, Cl, K, Mg, +/- Ca and Ph) are added to replace daily losses unless a particular value is specified. Aqueous multivitamin preparations are added to the dextrose-AA solutions. These MVI solutions contain the normal daily requirements for all but vitamin K, but hypermetabolic patients may require more than what standard solutions provide. Also beware as vitamin A is degraded by light and selenium is degraded by sulfite ions used as preservatives in the AA solutions [LaFrance RJ: TPN, Boston, Little 57, 1991]. Trace element mixtures are added as well and usually include Cr, Cu, Mn, Zn but do not contain iron or iodine. Some (but not all) contain selenium.
Creating a TPN Regimen
Step I: Estimate the daily protein and calorie requirements.
Step II: Take a standard mixture of 10% AA and 50% dextrose (500 mL) and figure out the volume needed to deliver the protein requirements.
Step III: Determine the total calories delivered by the above mixture.
Step IV: assume a 10% lipid emulsion (1kcal/mL) to provide the remainder of calories needed (I – III).
Daily TPN orders are rewritten each day. Be sure to specify electrolyte, vitamin, and trace element requirements as needed. A recent trend is to mix everything together, producing a total nutrient admixture (TNA) – this simplifies the process and reduces cost but there are lingering concerns regarding compatibility (ex. MVI may not be compatible with lipid emulsions).
Catheter complications, including infection, are possible. If a catheter is positioned in the IJV, withdraw it until ~ 3 cm remain. Send a guidewire through the catheter about 10 cm deep, then withdraw the catheter and place another one in 15 cm. Bolus saline through the new catheter and place a Doppler probe over the IJV, listening for flow. If no sound is detected, verify the correct position with an X-ray.
Glucose intolerance is one of the most common complications of TPN. It can be alleviated somewhat by using more lipids but usually requires the addition of insulin to TPN solutions. INSULIN ABSORBS TO ALL PLASTICS AND GLASS USED IN IV INFUSION SETS, with an average loss of 20 – 30% to be expected [Trissel LA. Handbook of Injectable Drugs. 585, 1994]. Albumin has been used to reduce insulin binding but this is costly and unreliable. Analysis of the VA [NEJM 325: 525, 1991] and other early studies [J Trauma 29: 916, 1989; Ann Surg 215: 503, 1992] suggest that the increased rates of infection associated with the administration of TPN could be largely attributed to overfeeding and/or resultant hyperglycemia [Crit Care Clin 17: 107, 2001]
Hypophosphatemia is a common occurrence, with PO4 levels dropping from 3.5 mg/dL on day 0 to < 1.0 by 10 days of TPN [Arch Intern Med 137: 203, 1977]
When glucose calories exceed daily requirements, fatty infiltration of the liver may result along with elevated transaminases [Lab Med 21: 97, 1990; Nutrition 7: 1, 1996]. It is not clear whether or not this process has any pathophysiologic consequences.
Hypercapnia is common and was generally thought to be due to excessive carbohydrates, but may be due to overfeeding in general [Chest 102: 551, 1992]
Lipid infusions increase the likelihood of oxidation-induced cell injury [Nutr Clin Pract 8: 55, 1993], and according to Marino this aspect of nutritional support should be studied further. Lipid infusions are also associated with impaired oxygenation [Crit Care Med 16: 183, 1988] – free fatty acids are known to damage pulmonary capillaries (think fat embolus, also oleic acid is used to produce ARDS in animal models).
Mucosal atrophy occurs in the absence of bulk nutrients, predisposing to bacterial translocation. Also, acalculous cholecystitis results from bile stasis.
Lipid infusions may increase the risk of oxidation-induced cell injury [J Surg 24: 1493, 2000] – oleic acid infusions are used to cause ARDS in rats [Am Rev Res Dis 149: 245, 1994], and lipid infusions have been associated with impaired oxygenation and prolonged respiratory failure [J Trauma 43: 52, 1997; Crit Care Med 29: 1569, 2001]
Early vs. Late Parenteral Feeding
Seven Belgian ICUs recently performed The Early Parenteral Nutrition Completing Enteral Nutrition in Adult Critically Ill Patients (EPaNIC) Study, a prospective, randomized, controlled, parallel-group, multicenter investigator-initiated trial (partially funded by Baxter) in which 4640 nutritionally at-risk patients were randomized to early (within 48 hours) vs. late (at least 8 days) initiation of parenteral nutrition (2007 to 2010). While the early nutrition group clearly received more nutrition (both in terms of total energy and percentage of target), the late group was discharged from the ICU one day earlier (p = 0.04), had a lower incidence of hypoglycemia (p = 0.001), fewer infections (22.8% vs. 26.2%, p = 0.008), and a reduction in total healthcare costs of ~ $1600 (€1,110). Mortality was the same. Importantly, mean units of insulin and average glucose in the early and late groups were 58U/107 mg/dL and 31U/102 mg/dL, respectively [Casaer MP et al. NEJM Jun 29 2011 [Epub ahead of print]; FREE Full-text at New England Journal of Medicine]
Two points deserve mentioning. First, this is the largest trial to date, dwarfing all previous trials. To make up for the lack of large RCTs, intensivists previously relied on data from metaanalyses to guide nutritional therapy. As of 2004 three metaanalyses compared EN to PN – Braunschweig et al (20 trials, 1033 subjects), Gramlich et al (13 trials, 807 subjects), and Simpson and Doig (11 trials, 688 subjects). Second, most of the studies from earlier trials preceded our increased appreciation for the importance of glycemic control (which changed radically with van den Berghe et al. NEJM 345: 1359, 2001). In the Belgian study, mean units of insulin and average glucose in the early and late groups were 58U/107 mg/dL and 31U/102 mg/dL, i.e. glycemic control was the same.
One early study suggested a benefit of early TPN in neurosurgical patients at [J Neurosurg 58: 906, 1983], another suggested more rapid recovery but ultimately no change in outcome [J Neurosurg 67: 668, 1987]. These studies may be biased by timid use of intragastric feedings secondary to over-restrictive gastric residual requirements.
48 patients with TBI randomized to early parenteral (TPN, n = 21) or jejunal (ENT, n = 27) feeding with identical formulations. Both routes were equally effective at meeting nutritional goals. Infections were equally frequent: 1.86 episodes/TPN patient versus 1.89 episodes/ENT patient [J Trauma 37:459, 1994]
Remember to give small dose enteral feeds concomitantly, if possible, as these will prevent mucosal atrophy.
Peripheral Parenteral Nutrition
Occasionally, parenteral nutrition can be delivered peripherally for a short while. Osmolality should be < 900 mOsm/L [Teasley-Strausburg KM: Nutrition Support Handbook: 37, 1992] and pH 7.2 – 7.4, thus the amino acid and dextrose solutions delivered must be dilute. The lipid emulsions can be standard as they are isoosmotic.
A common PPN mixture is 3% AAs, 20% dextrose producing a final concentration of 1.5%/10% and 500 mOsm/L. 2.5 L of this solution plus 250 mL of 20% Intralipid will produce 1350 kcal/day. This is an ideal temporizing measure for patients expected to begin feeding in a few days, ex. post-op patients.
Parenteral Feeding: Key Points
- Data in infection rate is largely due to poor glucose control and when this is accounted for, infectious complications are similar to enteral feeding [Crit Care Clin 17: 107, 2001]
- There are no large, randomized, controlled studies of TPN vs. enteral nutrition in the neurosurgical patient. Older studies are complicated by over-restrictive enteral feeding regiments and poor glucose control
- Remember to use the GI tract as well, if tolerated, to prevent mucosal atrophy
VITAMIN AND MINERAL SUPPLEMENTATION [Anstwurm MWA, Schottdorf J, Schopohl J, et al. Selenium replacement in patients with severe inflammatory response syndrome improves clinical outcome. Crit Care Med 27: 1807, 1999]: selenium and renal failure (reduces ARF but no change in mortality).[Transplantation 2005;80: 1363–1368]
(see Table 1 in text, not yet reproduced here)[Young B, Ott L, Kasarskis E, et al. Zinc supplementation is associated with improved neurologic recovery rate and visceral protein levels of patients with severe closed head injury. J Neurotrauma 13: 25, 1996]: this trial was flawed due to selection bias. [Heyland DK, Dhaliwal R, Suchner U, Berger MM. Antioxidant nutrients: a systematic review of trace elements and vitamins in the critically ill patient. Intensive Care Med 2005; 31:327—337]: systematic review of trials of trace elements and vitamins supports antioxidant function in critically ill patients. Using meta-analysis techniques, demonstrates that high-dose parenteral selenium either alone or in combination with other antioxidants are safe and may be associated with a reduction in mortality in critically ill patients.
Crimi et al. found a that supplementation with antioxidant vitamins C and E resulted in a significant reduction in mortality in critically ill patients [Crimi E, et al. Anesth Analg 2004; 99: 857—863; FREE Full-text at Anesthesia & Analgesia.