Khuroo MS, Yattoo GN, Javid G. A comparison of omeprazole and placebo for bleeding peptic u lcer. N Engl J Med 1997; 336: 1054 \200\2238. Lau JYW, Leung WK, Wu JC, et al. Omeprazole before endoscopy in patients with gastrointesti nal bleeding. N Engl J Med 2007; 356: 1631 \200\22340. Lau JYW, Sung JJY, Lee KKC, et al. Effect of intravenous omeprazole on recurrent bleeding a fter endoscopic treatment of bleeding peptic ulcers. N Engl J Med 2000; 343: 310 \200\2236. Rockall TA, Logan RFA, Devlin HB, et al. Incidence of and mortality from acute upper gastro intestinal haemmorrhage in the United Kingdom. BMJ 1995; 311: 222 \200\2236. Stiegmann GV, Goff JS, Michaletz Onody PA, et al. Endoscopic scle- rotherapy as compared wi th endoscopic ligation for bleeding oesophageal varices. N Engl J Med 1992; 326: 1527 \200 \22332. 78 PJ ALLEN & J BOOTH Nasojejunal feeding in critical care patients Who needs NJ feeding? Due to dif \201 culties placing and maintaining an NJ feeding system , the NG route should be used routinely, with NJ reserved for particular cases. The main in dications for a NJ feeding tube are post-gastric/oesophageal surgery and acute severe pancr eatitis, but patients with gastric atony or gastoparesis, who are at risk of aspiration, ma y also bene \201 t. The risk of aspiration due to NG feeding is 6.5% , whilst the risk of aspiration in NJ feeding is 2.4%. Consider percutaneous endoscopic gastrostomy (PEG) or per cutaneous endo- scopic jejunostomy (PEJ) in patients requiring long-term feeding (>4 \200 \2236 weeks). Combining NJ feeding with a gastric aspiration port helps to reduce gastric v olumes and so reduces the risk of aspiration. Critical care patients are often malnourished, due to either poor nutritional status prior to admission, inadequate calorie intake for nutritional needs or a combination of both. Ent eral nutrition (EN) helps the gut function normally and keeps the integrity of the mucosal barrier, and so decreases gut permeability, reducing the risk of bacteraemia and endotoxaem ia. Bacterial and toxin translocation is prevented by the barrier function of the small bow el mucosa, but this is com- promised early in the disease process of critically ill patient s, as demonstrated by increased gut permeability to polyethylene glycol. Studies of trauma, burns and major surgery patients have shown improved outcome with EN compared with total p arenteral nutrition (TPN), and this has been replicated with those with severe acute pancre a- titis. Furthermore, EN caused a reduced incidence of systemic in \202 ammatory response syndrome (SIRS), a reduced APACHE II score, C-reactive protein (CRP) and serum IgM antiend otoxin antibodies, but an increased total antioxidant capacity. Gastroduodenal dysmotility is a common problem in critical care and may result from the underlying illness, but also f rom medication such as sedatives or analgesics. Dysmotility prevents or reduces ef \201 ca cy of nasogastric (NG) feeding, and large gastric residual volumes place a patient at risk of re \202 ux, vomiting and aspiration. Nasojejunal (NJ) feeding can overcome these dif \201 culties, and enable the patient to receive suf \201 cient calorie intake. Methods 1. Bedside NJ insertion A simple NJ tube can be placed at the bedside by laying the patient at 30 \200\22345 . A motility stimulant (e.g. metoclopra- mide or erythromycin) c an be given 30min prior to inser- tion for improved insertion rates. Mark off the NJ tube a t the level of the stomach (40 \200\22345cm) and measure off another 25 \200\22330cm to all ow insertion into the jejunum. Pass the lubricated tube down the nose into the stomach and at the \201 rst marked point blow in air to con \201 rm placement. Roll the patient into the right lateral oblique position at the same angle for the head and continue advancing i nto the duodenum. Blowing in air now should produce \201 ne rather than harsh crackles. P lacement in the left lower lung in patients with pulmonary oedema or pneumonia can mimic th at of air blown in the stomach. Aspirates of \202 uid from the duodenum and beyond should be alkaline. Push to the sec- ond mark and con \201 rm the position using an abdominal ra diograph with or without contrast. Nutritional assessment and treatment General malnutrition (protein-calorie) can be assessed from the history (anorexia, dietary history, calorie intake) and examination (muscle wasti ng, oedema, angular stomatitis). Objective bedside measurements can include weight loss >10 % in the preceding 3 months, blood tests (albumin <35g/l, lymphocytes <1.5x109, transferrin <2g/l), skin fold tests (mid-triceps skin fold thickness <8mm in men and 17mm in women, an d mid-arm muscle circumference <30cm on men and 26cm in women) and a BMI <19kg/m2. Obese pa tients should receive nutritional treatment according to their ideal body weight for their height, with a 30% supplement for increased metabolic requirements in critical care setting s. There are several factors to consider for nutritional treat- ment: 1 Fluid balance 2 Ene rgy from fat and carbohydrates (30 \200\22360 kcal/kg/24h) 3 Nitrogen requirements (0.16 \200\2230.35g/kg/24h) 4 Electrolytes 5 Trace elements and vitamins Typical feeding regimes will need working out with hospital dieticians, but typical polymeric feeds are Jevity (Abb ott) and Osmolite (Abbott), which comprise protein, carbohy- drate, fat, vitamins and miner als. Continuous drip feeding reduces the complications of re \202 ux, aspiration or diar- rhoea. Starting rates should be in the order of 30ml/h and increased as the patient tolerat es. Additional \202 uid needs should be provided with water. Feed containers and giving s ets should be changed every 24h to prevent bacterial con- tamination. 2. Fluoroscopic insertion Move the patient to a suitable area for radiological screening. P ass an NJ tube using a guide wire and \202 uoroscopic screen- ing into the jejunum. Posit ion can be checked at the same time. 3. Endoscopic insertion In the critical care or endoscopy unit pass the gastroscope into th e duodenum. A nasobiliary guide wire (ERCP guide wire) is passed down the biopsy channel an d, once in the duodenum, pushed as far as possible past the second part into the jejunum. R emove the endoscope and maintain the wire in position either using screening or by insertin g it in a stepwise fashion by as much as the endoscope is removed. Once the endoscope is re moved, convert the orojejunal guide wire to an NJ wire by a naso-oral exchange. Pass a plas tic tube over the guide wire in a Seldinger method into the jejunum. Check the position wit h a contrast abdominal radiograph or by screening, and remove the guide wire. Evidence, disadvantages and alternative techniques Success rates for jejunal placement rema ins low at 14%, so techniques to make the insertion more reliable have been developed: weig hted ends, balloons and spiral cork- screws. ECG monitoring with a change in the polarity a s the tube passes the pylorus gives fast placement within 15min (range 7 \200\22375) with 6 5% placed the \201 rst time, and a further 79 CHAPTER 4.3 Nasojejunal feeding in critical care patients \200 \200 30% the second time. The rather expensive Cortrak system uses an external sensor to plot di agrammatically the position of the NJ tube, and an initial study found it correctly placed an NJ tube in 57/57 patients in a faster time, with reduced radiographic costs and shorter time delay to starting EN. Fluoroscopy can help correct placement of NJ tubes but is often not feasible in the critical care setting, with the need for radiological support, a lead-l ined room, being expensive and time consuming. Endoscopy is useful as it can visualize the upper GI tract, ensuring there are no contraindications to NJ feeding. An alternative techn ique to the one described passes the NJ tube into the stomach, the endoscope \201 nds it in the stomach and with forceps or a snare brings the tube through the pylorus into the duo denum and beyond towards the jejunum. Unfortunately the tube is easily dislodged on removin g the endoscope so this limits its usefulness. Try pro-kinetics. Would an NG tube satisfy feeding requirements? Should patient be consider ed for PEG/PEJ? Summary \200 NJ tubes rarely used, but a good way of achieving nutri- tional goals. NJ tubes are dif \201 cult to place consistently and easily, though new techniques are increasingly available. If emergency feeding needed consider NG feeding in the short term unless vomiting or risk of aspiration. Enteric feeding protects gut barrier integrity, is better, cheaper and safer than TPN; but TPN may bridge the gap until enteric feeding is possible. References Cohen LD, Alexander DJ, Catto J, et al. Spontaeous transpyloric migration of a b allooned nasojejunal tube: a randomized control- led trial. J Parenter Enteral Nutr 2000; 2 4: 240 \200\2233. Troubleshooting 1 NJ tube keeps slipping Davies AR, Froomes PR, French CJ, et al. Randomized comparison of nasojejunal and nasogastr ic feeding in critically ill patients. Crit Care Med 2002; 30: 586 \200\22390. Try a different ended tube such as weight/ balloon/ corkscrew to keep in the jejunum with p eristalsis. Use a prokinetic. Lai CW, Barlow R, Barnes M, Hawthorne AB. Bedside placement of nasojejunal tubes: a randomi zed-controlled trial of spiral- vs straight-ended tubes. Clin Nutr 2003; 22: 267 \200\22370 . Marik PE, Zaloga GP. Gastic versus post pyloric feeding: a systematic 2 NJ tube blocked review. Crit Care 2003; 7: R46 \200\22351. \200 Change tube for a new one. In future, \202 ush tube after each feed, after medications an d when not in use. (Unblock with water, soda water or 5% sodium bicarbonate.) Do not use fo r non-liquid medications or use an NG tube. Patrick PG, Marulendra S, Kirby DF, et al. Endoscopic nasogastric \200\223 jejunal feeding tube placement in critically ill patients. Gastrointest Endosc 1997; 45: 72 \200\2236. Pearce CB, Duncan HD. Enteral feeding. Nasogastric, nasojejunal, percutaneous endoscopic ga strostomy and jejunostomy: its indication and limitations. Postgrad Med J 2002; 78: 198 \200\223204. 3 NJ not positioning correctly \200 Check indication. Seek specialist help \200\224endoscopic or radiological. 4 Abdominal pain and distension Consider slowing feed or stopping for a short period This page intentionally left blank 81 Chapter 5 Nutrition Chapter contents Enteral nutrition 82 Parenteral nutrition 84 Immune-enhancing nutrition 86 82 J WERNNERMAN Enteral nutrition Is there a rationale for nutrition in the ICU? Nutrition is an important part of intensive care medicine. This may seem self-evident, but the lack of randomized controlled clinical t rials to document the usefulness of nutrition in the ICU has been pointed out. The fact tha t nutrition may be associated with adverse effects has led to some authors to the point whe re they question the use of nutrition as such in the ICU. However, the majority of intensiv ists are in favor of providing nutrition for their patients, basically relating to the fact that sooner or later any individual will starve to death without nutrition. The controvers y will then be when and how to provide nutri- tion for the patients. As for many different routines in the ICU, nutrition should also be protocolized, and exceptions from protocol sh ould be rare and well motivated. The nutritional routines should be well known by everybody working in the unit, and everybody should be well informed and hopefully unanimous behind the rationale for the particular routines used. cannot be compensated for later on, and very often the major part of an energy de \201 cit is built up during the initial 2 weeks of ICU stay. This is unfortunate because during the initial period of ICU stay, it is usually quite dif \201 cult to pre- dict which patients are going to be the real long-stayers. If this could be predicted with a high accuracy, th is would not be a problem, but unfortunately it is dif \201 cult and, once the accumulated energy de \201 cit is developed, it will stay as a burden of depletion for the patients. Overfeeding later on will worsen the problem rather than help. When to start nutrition Whenever the decision is taken to feed the intensive care patient, the feeding should be with a complete formula containing all macronutrients regardless of w hether the feeding is by the enteral or parenteral route. There are several standard formul as enriched with the proper vitamins and trace elements available on the market, usu- ally with a high content of \201 bres. Similarly there are several all-in-one combinations for parenteral nutrition (PN) to which there are supplements available containing water- and f at-soluble vitamins as well as trace elements. For most patients, these standard formulatio ns are the most appro- priate nutrition. For patients with excessive losses from \201 stu las as well as in burn injuries, there might be an elevated need for trace elements as well as for antioxidants. When patients are fed by the enteral route only, the success rate of enteral feeding is usually on the level 60 \200\22370%. This may not be a big problem if th e ICU stay will be less than a week with a perspective of resuming ordinary food intake wit hin a short time. However, if 100% of energy expendi- ture cannot be reached before the ene rgy de \201 cit gets out of hand, it is dif \201 cult not to give complementary parentera l feeding to meet the nutritional target. The length of stay is here the crucial factor. Th ere presently is not suf \201 cient documentation to show that a combination of enteral an d parenteral feeding to meet the nutritional target will decrease morbidity and mortality. The reason for this is that no such studies are at hand. Still, this is an often advo- cate d strategy for nutritional support in the long-staying ICU patient. Who is responsible for the nutrition? The decision when to initiate nutrition is a responsi bility of the intensivist. If the individual intensivist lacks the appro- priate competence , it is advisable to get in contact with a nutritional team, a dietician or any other exper t, just like in other cases when the intensivist may be in need of external advice. It is i mportant to integrate the feeding decision in the general medical strategy, taking the \202 uid balance, possible over- or underhydration and possible interfer- ences with medica tions or other types of treatment given into account. Furthermore, the decision whether or not to use the GI tract for nutrition is another responsibility of the intensivist. Access to the GI tract To assess the GI function is dif \201 cult, and there is no gener- ally accepted de \201 nition of the functionality of the GI tract. One suggestion is to ev aluate the GI function in terms of whether or not enteral feeding is possible. It has been suggested that successful enteral feeding on the level of 80% of the measured energy expend iture may be a proper de \201 nition of normal GI tract function. ICU patients are most of ten fed by nasogastric (NG) or nasojejujunal (NJ) tubes. There are several studies comparin g the two tech- niques, but there is no convincing evidence that one tech- nique is superio r to the other. In conjunction with surgical procedures, it is sometimes possible to insert a percutane- ous feeding jejunostomy, which might be helpful post-oper- atively in cases o f upper GI tract surgery. There is reasonably good evidence that an early start of enteral feeding is associated with a high success rate. This observa- tion is true regardless of fe eding technique or placement of feeding tube. How to estimate the caloric need The best way to estimate the caloric needs is to perform i ndirect calorimetry. If such readings are available, dosage of nutrition is no problem. How ever, in many institutions, this is not possible. Second best then is to have a measure- me nt of carbon dioxide production, which under stable circumstances can give a good estimate. However, over- feeding may give erroneously high values of energy expend- iture based on c arbon dioxide production, which it is not possible to discover without access to a calculat ed respira- tory quotient. In most cases it is advisable to start up with 20kcal/kg in elde rly people >65 years old and 25kcal/kg for younger people. Later on during ICU stay, some p atients may develop an extreme hypermetabolism, which some- times can be dif \201 cult to detect. If this hypermetabolism is not recognized and appropriately treated, an extreme acc umulated energy de \201 cit may develop, which has a high risk to be detrimental to the pa tient. Consequently for extreme long-stayers with multiple organ failure access to indirect calorimetry or at least a carbon dioxide production measurement may be crucial. Energy de \201 cit Recently there is accumulating evidence that a cumulated energy de \201 cit in long-staying ICU patients is a predictor of morbidity and even mortality. Energ y de \201 cit is the differ- ence between measured or estimated energy expenditure and the provided calories. A cumulated energy de \201 cit of >10 000kcal has in several studies b een shown to be asso- ciated with a high level of morbidity, even when adjusting for underl ying pathology. Unfortunately an energy de \201 cit 83 CHAPTER 5.1 Enteral nutrition A nutritional protocol In general terms, a robust feeding algorithm is to be preferred over a diversi \201 ed feeding regimen for different underlying disorders. The advantage of sp eci \201 c feeding routines for speci \201 c patient groups is not impressive. Still in a ddition to standard feeds for enteral or parenteral use, there are speci \201 c nutrients. Best documented in terms of morbidity and mortality is supplementation with glutamine. For patients needing PN, supplementation with IV glutamine containing dipeptides is demonstrat ed to give a survival advantage. This is therefore recommended in most guide- lines for pat ients on PN. Glutamine supplementation for patients on enteral nutrition (EN) is more contr oversial. morbidity and mortality in ICU patients who tolerate enteral feeding. The underlying mechan ism is claimed to be that omega-3 fatty acids have anti-in \202 ammatory properties. Altho ugh the documentation for these new products has been criticized, the dramatic effect shown cannot be ignored. Available studies are not conclusive as the control formula used has a very high lipid content. More conclusive studies will be needed before a general recommenda tion can be made concerning the omega-3-enriched formulas. Further reading Heidegger CP, Romand JA, Treggiari MM, et al. Is it now time to promote mix ed enteral and parenteral nutrition for the critically ill patient? Intensive Care Med 2007 ; 33: 963 \200\2239. Simpson F, Doig GS. Parenteral vs. enteral nutrition in the critically ill patient: a meta- analysis of trials using the intention to treat principle. Intensive Care Med 2005; 31: 12 \200\22323. Speci \201 c nutritional formulations On the European market there are today a number of d ifferent fat emulsions. All of them are demonstrated to be well tolerated, and several offe r considerable theoretical advantages. Unfortunately there are presently no clinical studie s with clinically relevant end-points that show a pref- erence for any speci \201 c IV fat emulsion. For enteral use there are omega-3 fatty acid-enriched formulas, which in a few r ecent single-center studies have been demonstrated to provide advantages in terms of both Villet S, Chiolero RL, Bollmann MD, et al. Negative impact of hypoc- aloric feeding and ene rgy balance on clinical outcome in ICU patients. Clin Nutr 2005; 24: 502 \200\2239. Wernerman J. Intensive care unit nutrition \200\224nonsense or neglect? Crit Care 2005; 9: 251 \200\2232. Wernerman J. Guidelines for nutritional support in intensive care unit patients: a critical analysis. Curr Opin Clin Nutr Metab Care 2005; 8: 171 \200\2235. 84 NA BARRET & R KEAYS Parenteral nutrition Requirements Electrolytes (/kg/day) Nutrition is an essential component of the supportive ther- apies offered by intensive ther apy units (ITUs). Nutritional support improves wound healing, decreases the catabolic respo nse to injury and improves clinical outcomes, includ- ing a reduction in complication rates and length of stay. Enteral nutrition (EN) is preferred over parenteral nutrition (PN) bec ause EN has lower infectious complications, is easier to use and cheaper. However, not all patients are suitable for EN. Water Sodium Potassium Calcium Magnesium Phosphorus 30ml 1 \200\2232mmol 0.7 \200\2231mmol 0.1mmol 0.1mmol 0.4mmol Indications \200 Gastrointestinal failure of any cause (e.g. major abdomi- nal surgery, t rauma or sepsis with a consequent pro- longed ileus, short bowel syndrome, enteral \201 s tulae). \200 PN may be required in acute pancreatitis (although EN via a jejunal feeding tube has a signi \201 cantly lower risk of infectious complications, and shorter duration of hospi- talization, consequently EN is preferred). Carbohydrate 3 \200\2234g/kg/day Glucose is the optimal carbohydrate in PN and should provi de 60% of non-protein calories. Lipid Approximately 40% of non-protein calories should derive from lipid. Lipids are essent ial for cellular homeostasis and immune function. Lipids are available as long chain trigly cer- ides or medium chain triglycerides, and mixtures of the two. There is insuf \201 cien t evidence at present to suggest that any single lipid formulation provides a clinically si gni \201 cant bene \201 t over others. Inability to absorb EN. Commencement There is some evidence that early nutrition has a mortality bene \201 t over delayed nutrition. Consequently PN should be commenced during the \201 rst 24 \200\22348h of an ITU admission if EN is contraindicated. If EN is not absorbed (including after a tri al of promotility agents) then PN should be com- menced as soon as possible because PN may have survival advantages over delayed EN (>7 days). Protein 1 \200\2231.5g/kg/day, 1.5 \200\2232g/kg/day for patients with catabolic illnesses including burns. Protein should be a mixture of essential and non-essential amino acids. A recent meta-analysis suggests that glutamine as part of a PN regime may give a survival ben e \201 t, although it will not decrease infectious complications. As yet no clinically sig ni \201 cant bene \201 t has been demonstrated with branched chain amino acids. Cessation Daily review of PN continuation is required. There may be a period where EN and P N are co-administered while establishing EN. Once GI function has recovered, PN is best wit hdrawn over a period of 24 \200\22348h to avoid rebound hypoglycaemia. If rapid cessation o f PN is required, frequent blood glucose monitoring is required and a 5% dextrose infusion should be used to maintain normoglycaemia. Vitamins and essential elements (daily requirement) The optimal requirement for vitamins an d essential ele- ments in the critically ill or in PN is unclear. The recom- mended daily a llowance of vitamins and essential elements is (Food and Drug Administration): Vitamin A Vi tamin D Vitamin E Vitamin C Vitamin K Folic acid Nicotinamide Ribo \202 avin Niacin Thiami ne Pyridoxine Cobalamin Pantothenic acid 5mg Biotin Chromium Copper Fluoride Iodine Dose The daily calorie requirement of patients in ITU is dif \201 cult to assess. Importan t in the assessment is a nutritional history, underlying medical conditions and presenting problems to the ITU. Anthropomorphic measurements can be used; however, they can be dif \201 cult and unreliable in ITU patients. Measurements of serum albumin, prealbumin, ferrit in and lymphocytes are all unreliable as they are independently impacted upon by acute illn ess. Other methods to assess caloric requirements include predictive equations such as the Harris \200\223Benedict equation and indirect calorimetry. Urinary nitrogen can be measured to assess protein losses; however, given that protein loss varies on a day-to-day basis, t he delay in measurement and altering the make-up of the PN bag makes this impractical. Burn s, major trauma and sepsis are all hypermetabolic and catabolic states. Major burns may inc rease the caloric requirement by up to 150% of baseline and increase protein catabolism. Gi ven the dif \201 culties in estimating an individual \200\231s caloric requirements, many practitioners give 25 \200\22330kcal/kg/day and alter the dose depending on individual pati ent circum- stances as this has been shown to be as accurate as more complex approaches. 700 \200\223900mcg 5mcg 15mcg 75 \200\22390mg 90 \200\223120mcg 400mcg 40mg 1.3mg 16mg 1.2m g 1.3mg 2.4mcg 30mcg 20 \200\22335mcg 900mcg 3 \200\2234mg 150mcg 85 CHAPTER 5.2 Parenteral nutrition of hepatic problems varies with duration of PN. Steatosis and cholestasis may relate to exc essive caloric provision, but there is evidence that choline de \201 ciency may be impor- tant. Both hepatic steatosis and cholestasis usually follow a benign course, although they may require reduction in PN rate. Iron Manganese Molybdenum Selenium Zinc There is evidence that the use of selenium and anti oxidants to supplement PN improves mortality without decreasing infection rates, ITU length of stay or length of ventilator dependence. Consequently supplementation of PN with seleni um and antioxidants may be considered. Supple- mentation with zinc above baseline requireme nts has not been shown to improve mortality. 8 \200\22318mg 1.8 \200\2232.3mg 45mcg 55mcg 8 \200\22311mg Hyperglycaemia: there is increasing evidence that strict glucose control in critical illnes s leads to reduced mor- bidity and mortality (from 8 to 4.6%) in surgical patients with blo od glucose maintained from 4.4 to6.1mmol/l. \200 Rebound hypoglycaemia with sudden cessat ion of PN infusions. Refeeding syndrome: monitor potassium, magnesium, phosphate and calcium levels, especially in patients who are malnourished Formulations Standard formulations of PN are available in combination bags that require tho rough mixing before infusion. Most formulations contain 40% of non-protein calories as lip id, and 60% as carbohydrate with added amino acids, vitamins and trace elements. Most formu lations can have the elec- trolyte concentration altered depending on clinical circum- stan ces, and additional trace elements and vitamins may be added. Lipaemia: if lipaemia is a signi \201 cant problem the rate of PN can be reduced or the li pid component reduced or removed. Relating to de \201 ciencies Common de \201 ciencies are thiamine (wet or dry beri-beri o r lactic acidosis) or vitamin K (hypocoagulable states); how- ever, all vitamins and trace element de \201 ciencies may develop. Patients on RRT are particularly at risk of de \201 ciencies of water-soluble vitamins. Investigation Daily \200 Blood glucose estimation 1 \200\2234 hourly as indicated by Further reading Atkinson M, Worthley LIG. Nutrition in the critically ill patient: Part I. Essential physiology and pathophysiology. Crit Care Resus 2003; 5: 109 \200\22320. blood glucose stability Electrolytes (including calcium, magnesium, phosphate, sodium, potassium, urea) Buchman A. Total parenteral nutrition-associated liver disease. J Parenter Enteral Nutr 2002; 26: S43 \200\2238. Liver function tests \200 Full blood count \200 Coagulation screen Monthly \200 Trace elements (selenium, zinc, molybdenum, manganese, Heyland DK, Dhaliwal R, Drover J, et al. Canadian clinical practice guidelines for nutritio n support in mechanically ventilated, criti- cally ill adult patients. J Parenter Enteral N utr 2003; 27: 355 \200\22373. Heyland DK, Dhaliwal R, Suchner U, et al. Antioxidant nutrien ts: a systematic review of trace elements and vitamins in the criti- cally ill patient. Int ensive Care Med 2005; 31: 327 \200\22337. copper, iron) Marik PE, Zaloga GP. Meta-analysis of parenteral nutrition versus enteral nutrition in pati ents with acute pancreatitis. BMJ 2004; 328: 1407 \200\22312. Complications Relating to access \200 Complications of insertion \200 Catheter-related bloodstream infection \200 Central vein thrombosis Relating to infusions \200 Infection rates are increased in PN compared with EN. \200 Liver abnormalities: incudes hepatic st eatosis and chole- stasis, and hepatic failure may rarely occur. The incidence Simpson F, Doig GS. Parenteral vs. enteral nutrition in the critically ill patient: a meta- analysis of trials using the intention to treat principle. Intensive Care Med 2005; 31: 12 \200\22323. 86 C COLLINS Immune-enhancing nutrition Immune-enhancing nutrition (IEN) describes feeds that are enriched with speci \201 c \200 \230functional \200\231 nutrients thought to aug- ment or modify beneficially immune functi on and the in \202 ammatory response in order to improve clinical out- come. This is parti cularly pertinent in the ICU patient where the relationship between malnutrition, immune de \201 - ciency and nosocomial infection has long been recognized. Nutrients considered \200\230immune-enhancing \200\231 include the amino acids arginine and glutamine, omega-3 ( \2113) fatty acids, dietary nucleotides and antioxidant vitamins and min- erals, usually c ombined within IEN. Their immune-modifying effects appear to be dose depend- ent, confoundi ng clinical outcome measures generated from intention-to-treat (ITT) results vs subgroup an alysis based on delivery of an arbitrary \200\230threshold \200\231 of feed delivery. Rese arch on IEN includes formulated immune- enhancing feeds or the ad hoc addition of one or mo re nutrients to an enteral formula. Such heterogeneity of IEN makes global recommendations for use dif \201 cult. Omega-3 polyunsaturates The omega-3 ( \2113) long chain polyunsaturated fatty acids (PUFAs) eicosopentanoic acid (EPA) and docosohexanoic acid (DHA) generate potent immunomodulatory activities via direct competition with arachidonic acid \200\224an \2116 PUFA \200\224in t he production of eicosanoids. Eicosanoids derived from \2113 PUFAs such as prostacyclin PG I3 and leukotriene B5 (LTB5) downregulate in \202 ammatory proc- esses, in contrast to the proin \202 ammatory eicosanoids derived from \2116 PUFAs, such as LTB4. Competitive sup- pression of LTB4 reduces monocyte generation of key inflammatory mediators such as cytokin es IL-1B, IL-6 and tumor necrosis factor (TNF), ameliorating in \202 amma- tory eicosanoid production. \2113 PUFAs offset the proin- \202 ammatory effects of high-dose arginine-s upplemented IEN. GLA (g -linolenic acid) Metabolism of GLA (an \2116 PUFA) to di-homo- -linolenic acid (DG LA) blocks formation of proin \202 ammatory leukot- rienes from arachidonic acid metabolit es. DGLA is the pre- cursor of the less inflammatory prostaglandin E1 and thromboxane A1, a nd augments the effect of long-chain \2113 PUFAs. Standard feeds and immune effect A confounding factor of IEN is that standard feeds per se attenuate injury-related catabolism, maintain structural and functional integrity of the GI tract, reduce infectious compli- cations and improve wound healing rates. Early enteral fe eding (i.e. within 24h of ICU admission) is associated with a signi \201 cant reduction in infectious complications. Feeding within 48h of ICU admission signi \201 cantly reduces I CU mor- tality by 20% and hospital mortality by 25% in ventilated medical patients despite being independently associated with risk of ventilator-associated pneumonia. This bene \201 cial reduction in mortality exceeds that currently achieved by the use of IEN. Nucleotides Required by rapidly dividing cells, nucleotides improve immune parameters in ex perimental animal models and supplemented neonatal feeds. There is no evidence that nucleot ides alone confer bene \201 t to the critically ill patient except when included within IE N formula. Antioxidant micronutrients Emerging evidence suggests a reduction in 28 day mortality in su rgical ICU patients given continuous EN with supple- mentary infusions of vitamins C and E. Selenium infusions may reduce the mortality rate in patients with septic shock and severe sepsis. Immune-modifying nutrients L-Arginine L-Arginine is a \200\230conditionally essential \200 \231 amino acid during metabolic stress and sepsis. Low circulating L-arginine levels give rise to the views of sepsis as an L-arginine-de \201 cient state or a syndrome of excess n itric oxide, a vasoactive product of L-arginine metabolism. Arginine upregulates macrophage phagocytic activity and neutrophil production of reactive oxygen species (such as peroxyni trite). High level supplementation (above 12g/l) reduces infectious complications and enhan ces wound healing in elective surgery, but conversely can augment rather than subdue the in \202 ammatory response. Patient groups Medical patients Patients with primary lung failure from chest infection or smoke inhalation injury have an increased mortality with IEN. IEN does not appear to bene \201 t this group. Pre-surgical patient Pre-operative IEN given to upper GI cancer patients reduces post-opera tive infectious complications, but not mortality. ITT evidence is currently less than compe lling and there are signi \201 cant \202 aws in the design of recent studies. Glutamine The most abundant circulating amino acid in the extracellular and intracellular c ompartments becomes \200\230conditionally essential \200\231 during critical illness as pl asma glutamine levels fall. Several controlled studies and a meta-analysis have con- \201 rmed glutamine \200\231s bene \201 cial in \202 uence on the in \202 ammatory response, oxidative stress and gut integrity. The preferred energy substrate for rapidly dividing en terocytes and immune cells, it may also improve glucose metabolism by reducing insulin resi stance, and is also a precursor of glutathione. Supplementary enteral glutamine fails to de monstrate clear clinical bene \201 t, except in the trauma or burns patient where it is a recommended addition. Post-surgical patient The incidence of acquired infection and hospital length of stay (LOS) are signi \201 cantly reduced in elective surgery patients given IEN, although reduction in septic complica- tion rates are non-signi \201 cant and overall mortality rates similar . Patients requiring ICU whilst being fed IEN demon- strated a trend for increased mortalit y. Trauma Trauma patients are likely to be the most well nourished of critical care patients. IEN lowers the incidence of bacterae- mias and intra-abdominal infections, but other infect ious complications remain unchanged. 87 CHAPTER 5.3 Immune-enhancing nutrition Further reading Angstwurm MW, Engelmann L, Zimmermann T, et al. Selenium in Intensive Care (SIC): results of a prospective randomized, placebo-controlled, multiple-center study in pa tients with severe systemic in \202 ammatory response syndrome, sepsis, and septic shock. Crit Care Med 2007; 35: 118 \200\22326. Sepsis The potential bene \201 t of L-arginine-enriched IEN is limited to mild sepsis (APA CHE II score 10 \200\22320) rather than those with a pre-existing enhanced in \202 ammator y response present (i.e. severe sepsis or SIRS). Subgroup analysis con \201 rms a signi \201 - cantly higher mortality in septic patients receiving IEN com- pared with control fee d. Comparing IEN with parenteral nutrition, subgroup analysis of severely septic patients d emonstrated a 3-fold increase in mortality compared with controls. Co f \201 er M, D chelotte P. The role of glutamine in intensive care unit patients: mec hanisms of action and clinical outcome. Nutr Rev 2005; 63: 65 \200\2239. Crimi E, Liguori A, Condorelli M, et al. The bene \201 cial effects of anti- oxidant suppl ementation in enteral feeding in critically ill patients: a prospective, randomized, double -blind, placebo-controlled trial. Anesth Analg 2004; 99: 857 \200\22363. ARDS High-fat respiratory feeds reduce PaCO2 and VCO2 in ALI and ARDS by altering the respi ratory quotient and metabolic load of the feed. Use of an IEN respiratory feed (rich in \2113 EPA and \2116 GLA plus antioxidant vitamins) vs a \200\230standard \200\231 respira tory formula to address the underlying in \202 ammatory pathogenesis of ARDS signi \201 c antly reduced ventilator days, incidence of organ failure and ICU LOS, with a trend towards reduced mortality, despite signi \201 cant patient heterogeneity. Kalil AC, Danner RL. L-Arginine supplementation in sepsis: bene \201 - cial or harmful? Curr Opin Crit Care 2006; 12: 303 \200\2238. Kieft H, Roos AN, van Drunen JD, et al. Clinical outcome of immu- nonutrition in a heteroge neous intensive care population. Intens Care Med 2005; 31: 524 \200\22332. Kreymann KG, Berger MM, Deutz NE, et al. ESPEN guidelines on enteral nutrition: intensive care. Clin Nutr 2006; 25: 210 \200\22323. McCowen KC, Bistrian BR. Immunonutrition: problematic or prob- lem solving? Am J Clin Nutr 2003; 77: 764 \200\22370. Montejo JC, Zarazaga A, Lopez-Martinez J, et al. Immunonutrition in the intensive care unit . A systematic review and consensus state- ment. Clin Nutr 2003; 22: 221 \200\22333. Summary Globaly, IEN reduces the risk of infection complications, time on mechanical ventil ation, ICU LOS and hospital LOS in selected patient groups, but has no appreciable effect o n mortality. Variations in the nutrient pro \201 le of IEN feeds (particularly with regard to the level of arginine supple- mentation), errors in trial design, underpowered studies and post hoc interpretation of trial results all create dif \201 cul- ties in recommending IEN to the heterogenous ICU popu- lation. The influence of early and appropriate enteral f eeding per se may be of greater clinical relevance than IEN on positive outcomes in the cri tically ill patient. Sakr Y, Reinhart K, Bloos F, et al. Time course and relationship between plasma selenium co ncentrations, systemic in \202 ammatory response, sepsis, and multiorgan failure. Br J Ana esth 2007; 98: 775-84. This page intentionally left blank 89 Chapter 6 Respiratory monitoring Chapter contents Pulmonary function tests in critical illness 90 End-tidal CO2 monitoring 92 Pulse oximetry 94 90 S SINGH Pulmonary function tests in critical illness Introduction Pulmonary function test results in critically ill patients can be important pr ognostically and guide ventilatory and weaning strategies. However, they are not straightfo rward to measure in mechanically ventilated patients and remain limited to dynamic volumes. Fortunately, most modern mechanical ventilators are able to calculate and display static a nd dynamic lung volumes, together with derived val- ues for airway resistance, compliance a nd \202 ow/volume/ time curves. The ability to monitor these changes after altering venti latory parameters has enabled more sophisti- cated adjustments of ventilation, to prevent p otentially damaging mechanical ventilation. Spirometry measures dynamic lung volumes. This is most useful when assessing the severity of obstructive lung dis- eases (especially asthm a, COPD and obliterative bronchi- olitis). Lung volume measurements by body box plethysmogr aphy (gold standard) or helium dilution (prone to under-repre- sentation in bullous lung di sease or signi \201 cant gas trapping) detect hyperexpansion or restrictive lung diseases (i.e. small lungs, in \202 ammation or \201 brotic lung disease, or abnor- malities of t he muscles or skeleton of the chest wall).