9783939069478_leseprobe

Page 1

6MZ CQ^ZQ^YMZ

:a`^U`U[Z

5/A Za`^U`U[Z ĎĖĕď Twenty-five years ago intravenous nutrition was coming into general practice in the ICU. Many of the difficulties along the road seemed to have been solved at that time. Central venous lines were in widespread use, and nutritional products for enteral as well as parenteral use were commercially available. Devices to measure energy expenditure by indirect calorimetry were in use, and it was generally recognised that critical illness was associated with hyper-metabolism. Under the heading of “bigger is better,” so-called “hyper-alimentation” was launched. This meant that patients were provided as much as 150 % of their caloric need. Hospital starvation seemed to be something from the Dark Ages, which would no longer happen anymore, at least not in the ICU. At this time, fat emulsions for intravenous use had been available in Europe for 20 years, but intravenous fat was relatively newly registered for use in North America. There was a general reluctance in North America to use fat emulsions, instead concentrated glucose solution was most often used together with amino acid solutions. At the same time, it was very popular in Europe to use a mixture of different sugars as the carbohydrate source of energy. Naturally this over-enthusiasm mostly linked to parenteral nutrition had to sober up. It was

soon demonstrated that central venous lines used for intravenous nutrition were often associated with line sepsis. It was also demonstrated that caloric over-feeding, “hyper-alimentation,” was associated with a lot of problems. By the intravenous route patients were more or less force-fed, resulting in increased heat production and often an elevated body temperature [Carlsson and Burgerman 1985]. This was measured as fever and sometimes treated with antibiotics. Unfortunately, the results from indirect calorimetry were not used to administer suitable amounts of calories, but instead an extra allowance was added and patients were frequently over-fed. The levels of energy expenditure measured and reported in those days were higher compared to what is seen today [Wilmore 1977]. This was probably a reflection of the standard of patient care at that time. In particular, burn patients, trauma patients and also ARDS patients in general showed a higher energy expenditure at that time than they do today. Today, they are treated differently in many respects, better handling of burn wounds and fractures, better pain control, more adequate volume resuscitation and so on and so forth makes a big difference today compared to those days. Approximately 25 years ago it also became obvious that micronutrients played an important role. Already at the start of hospital nutrition, today 50 years ago, enteral feeding with red rubber

3

-$ 3QZQ^MX UZ`QZ_UbQ OM^Q YQPUOUZQ

tubes in the stomach had proven its insufficiency. If enteral feeding was insufficient, the alternative was dextrose solutions in peripheral veins with steel needles. The time period after that provided sufficient calories and sufficient amino acids to the patients, sometimes even more than sufficient as pointed out above. Before micronutrients were given attention, case reports were published disclosing almost every shortage of vitamins or trace elements that is known. This happened when patients were kept alive for a long time by providing all the necessary macronutrients without the micronutrients. Approximately 25 years ago the necessary additives of micronutrients started to become commercially available. The science of ICU nutrition 25 years ago was also different from today. It was common to evaluate nutrition by calculating the nitrogen balance, a technique difficult to perform and difficult to interpret in the ICU [Munro and Allison 1963]. In terms of metabolic stress, patients undergoing elective surgery or suffering from acute trauma or sepsis were not properly separated. At that time it was common to look upon the metabolic alterations associated with elective surgery as just a mild variety of the same alterations that appeared in trauma and sepsis and which later on were associated with multiple organ failure. It was approximately at this time point that patients with ARDS survived long enough to develop multiple organ failure in the sense we know it today. At that time nutritional studies in the ICU focusing on outcome were not very common. The major academic disagreements at that time were enteral versus parenteral nutrition, glucose system versus lipid system and the cost effectiveness of parenteral nutrition or nutrition as such. As we all know, these major controversies are not that much different from then as they are now.

9MV[^ MOTUQbQYQZ`_ Pa^UZS ďĒ eQM^_ The major achievements in nutrition between 1982–2007 are: 1) better technical devices for both enteral and parenteral nutrition, 2) all-in-one formulations for parenteral nutrition, 3) Glutamine supplementation to parenteral nutrition, and 4) tight glucose control. In addition, there have been a number of other achievements with a less clear impact that will be discussed below.

4

For parenteral nutrition, one weak point over the years has been catheter sepsis. The rate of catheter-related infections is sometimes very high, and in particular central venous lines used for intravenous nutrition are more susceptible than those not used for that type of infusion. This is, however, an issue with several dimensions. Today catheter-related infections are suggested to be a quality indicator in intensive care medicine. Proper routines for the insertions of central venous lines, hygienic routines for handling the central venous lines as well as the strict routines for the use of the line – all of them matter [Hammarskjold et al. 2006]. It is demonstrated that skill of insertion and the number of attempts needed to obtain an intravascular placement matters for the frequency of complications. Today’s standard is that central venous lines are introduced under the sterile conditions of an OR, done by an appropriately trained person using an ultrasound device to identify the vessel. In that situation, intravascular placement should be achieved on the first attempt and without contamination. The hygiene standard for maintaining central venous lines should include regular changes of connecting devices under sterile conditions. All singular injections should be made through bacterial filters and connectors should not be placed in the bed of the patient. Separate lumen should be used for nutrition and for blood products only. In addition central venous lines may not be changed over guide wires unless there are special indications. In many countries today one of the major issues in the ICU round each day is whether or not the central venous line should be kept. The use of peripheral lines in the ICU is more common today that it used to be. Additionally, the procedures around peripheral lines has improved with better routines and restrictions around how many attempts may be done to introduce peripheral lines and thereby potentially destroy peripheral vessels [Berg et al. 2002]. Also for enteral feeding technical equipment has improved. The synthetic materials are softer, not causing pressure wounds in the nasal cavity or throat. The disadvantage of thin feeding catheters is that the residual volume in the stomach cannot be appropriately detected. Many centres today have good routines for inserting catheters for post-pyloric feeding. Jejunal catheters are placed with the patient in the lateral position using guide wires or by using endoscopy, or

-

:a`^U`U[Z

sometimes during surgical procedures as a feeding jejunostomy. In the early days of parenteral nutrition the components were delivered individually and given separately simultaneously or mixed together in the hospital pharmacy. Today there are several commercially available all-in-one formulations. The convenience of all-in-one formulation is obvious and there are also economic advantages compared to the all-in-one formulations prepared by the hospital pharmacy, and it saves time for the nurses in the ICU. The disadvantage of all-in-one formulation is that nutritional support is less individualised. Still, the convenience associated with all-in-one probably gives more patients in the ICU an adequate nutrition. Glutamine is not a constituent in conventional amino acid solutions for intravenous use. This is related to glutamine being unstable in aqueous solution, a problem now solved by the use of synthetic dipeptides. In intravenous nutrition studies of patients confined to intravenous nutrition, a benefit in terms of survival for glutamine supplemented nutrition is demonstrated [Griffiths et al. 1997, Goeters et al. 2002, Novak et al. 2002]. For patients for whom it is possible to feed by enteral route this advantage is less clear [Novak et al. 2002]. Some studies show effects upon infectious morbidity, other studies show no difference between groups. This is probably related to the level of glutamine depletion. It is demonstrated that low plasma glutamine, as a reflection of glutamine depletion, is associated with a higher hospital mortality, independently from the APACHE II score [Oudemans-van Straaten et al. 2001]. Identification of this subgroup of ICU patients for glutamine supplementation is probably crucial, and it is preferably done by lab tests. If lab tests are not available it is advisable to give glutamine supplementations to all patients receiving at least intravenous feeding. The singular most influential intensive care medicine study during the last 25 years is the demonstration by Prof. Greet van den Berghe that tight glucose control gives better survival [van den Berghe et al. 2001]. This was done in a single unit study but appropriately powered to demonstrate the survival benefit. The initial publication was in surgical patients, preferably patients undergoing open heart surgery. The benefits in terms of survival were also associated with a benefit in mor-

bidity in terms of less infections, less need for renal replacement therapy, less days on a ventilator and less critical illness myopathy/neuropathy. Five years later, still in a single centre study, Prof. van den Berghe demonstrated that the same was true for long-stay ICU patients with medical diagnoses [van den Berghe et al. 2006]. However, in that study the patients with a short ICU stay did not show any benefit. Although insufficient in number for a conclusive statement there was a tendency that these patients may even be at a disadvantage. Among the ICU patients with medical diagnoses, the incidence of hypoglycaemia was considerably higher as compared to the surgical patients. Furthermore, two other multi-centre studies in Europe were prematurely stopped for safety concerns because of the high incidence of hypoglycaemia (www.clinicaltrials.gov VISEPtrial and Glucontrol study). None of these other two studies demonstrated any benefit of tight glucose control as reported in preliminary data at recent congresses. Although there was a high incidence of hypoglycaemia in these studies also, this was not directly related to mortality. The patients included in Prof. van den Berghe’s study were properly fed during insulin treatment, something less well-documented in the other two studies. Another possible difference is whether or not the patients in the treatment group actually were subjected to normoglycemia. Among the reasons to prematurely stop one of the studies, beside the frequency of hypoglycaemia, was also the protocol violation of not separating the intervention group from the control group properly. Thus, today there is still confusion on this matter. Nevertheless Prof. van den Bergh’s studies clearly show that metabolic care makes a difference. Normoglycemia has been shown earlier to be beneficial in acute myocardial infarction on insulin dependent diabetics and in women giving birth. It is clearly difficult to obtain a strict normoglycemia in ICU patients, which is the challenge for the future.

1d\Q^UQZOQ_ [Z `TQ cMe Pa^UZS ďĒ eQM^_ Already from the very start synthetic fat emulsions, aiming to imitate the endogenous chylomicrons, were subject to problems. In Europe the development of Intralipid® into a commercial product used in clinical settings was not accom-

5

-$ 3QZQ^MX UZ`QZ_UbQ OM^Q YQPUOUZQ

panied by a similar development in North America. The fat emulsions tested for clinical introduction in North America failed to show sufficient safety. Patients had severe allergic reactions and these products never made it to the market. The negative attitude towards fat emulsions as unsafe has therefore stayed on. In addition IntralipidÂŽ, with a high content of omega-6 fatty acids is claimed to have immune-compromising effects. There is a large literature of experimental evidence demonstrating negative effects of long chained omega-6 fatty acids on various aspects of immune function. There are also published cases in clinical practice where this might have been the case. Unfortunately, there are no prospective randomised clinical trials which demonstrate this negative effect in clinical practice. In order to improve immunological function several enteral formulas have been launched under the heading of immuno-nutrition or immune-enhancing nutrition. These formulas are enriched in their content of arginine, omega-3 fatty acids, nucleotides, antioxidants and sometimes glutamine. A number of clinical studies have been performed in patients undergoing elective surgery and in ICU patients. For the surgical patients, out of the scope of this chapter, there seems to be a general beneficial effect [Heyland and Samis 2003]. However in the ICU patients the results of these studies have been very disappointing. Several studies even point out the possibility that such formulas may cause harm in subgroups of ICU patients [Bower et al. 1995, Bertolini et al. 2003, Dent et al. 2003]. The studies have several inherent problems including the difficulty of adequate feeding by the enteral route. Overall, the results can be summarised as that these formulas have no place in the intensive care unit. For omega-3 fatty acids, there is a lot of experimental evidence demonstrating an antiinflammatory effect. This may be attributed to omega-3 fatty acids having a beneficial effect upon prostaglandin and thromboxane systems. Furthermore, omega-3 fatty acids incorporated into biological membranes in the body may have antiinflammatory properties. Clinical studies give evidence for extra supplementation of omega-3 fatty acids by the enteral route. In ARDS patients, the number of ventilator days as well as oxygenation index is shown to decrease, and in a recent study of sepsis patients the mortality is shown to decrease [Gadek

6

et al. 1999, Pontes-Arruda et al. 2006, Singer et al. 2006]. The latter study shows a remarkable effect on outcome with the numbers needed to treat to be 6, which is an extraordinary clinical effect that needs to be confirmed in future studies. The controversy of the route of administration for ICU nutrition unfortunately persists. Part of the controversy is which evidence is relied upon. There are two major meta-analyses that come to opposite conclusions [Heyland et al. 2003, Simpson and Doig 2005]. The two meta-analyses basically reviewed the same studies (fig. 1). The difference is how they interpret the evidence from the reviewed studies, and what significance they give to the different pieces of evidence. In Dr Heyland’s meta-analysis the result is that there is no difference in mortality combined with a benefit for enteral nutrition in terms of morbidity. Drs Simson and Doig come to the conclusion that there is an advantage in terms of mortality for parenteral nutrition. This is of course frustrating, but this difference is clearly attributable to which patients are discussed. Several studies in the literature include patients who were possible to feed by the enteral route, and who should have been fed accordingly, but who were randomised to receive parenteral nutrition. Several studies also report an unacceptably high level of catheter-related infections. In one study, where the function of the gastrointestinal tract was used as criterion for inclusion to randomisation, the result is in a way remarkable. [Woodcock et al. 2001]. It both points out how difficult it is to assess the function of the gastrointestinal tract, and it also points out that ability to feed by the enteral route might be the best criterion for a functioning gastrointestinal tract. Nevertheless, when patients with an uncertain function of the gastrointestinal tract were randomised the number of complications, the morbidity, was lower for the group receiving enteral nutrition. However, at the same time, mortality showed a strong tendency to become higher. In that study, as well as in many more studies, it is obvious that the longer the patient stays in the ICU, the larger the number of complications, regardless of the route of feeding. This particular study is small in terms of the number of patients, which were randomised, and it is therefore inconclusive. However, in all other studies where patients have been randomised have not had this particular criterion addressed. This gives a back-

-

:a`^U`U[Z

<: 1: Z%: Z%: Ä?%Ä?Ä? ÄŽ%Ä?Ä? ÄŽ%Ä?ÄŽ Ä’%Ä?Ä• Ä•%Ä?Ä’ Ä”%Ä?ÄŽ ÄŽ%ÄŽÄ’ ÄŽ%ÄŽÄ? Ä“%ÄŽÄŽ Ä?%ÄŽÄ? Ä?%Ä?Ä‘ Ä?%Ä?ÄŽ Ä?%Ä?Ä? ÄŽ%ÄŽÄ• ÄŽ%Ä‘Ä’ ÄŽ%Ä’ÄŽ Ä•%ÄŽÄŽÄ• ÄŽÄŽ%ÄŽÄŽÄ? Ä?%Ä?Ä? Ä–%ÄŽÄ• Ä’%Ä?ÄŽ Ä–%ÄŽÄ” ÄŽÄ?%Ä?Ä• ÄŽÄ?%Ä?Ä?

CQUST` Ä?$Ä’ Ä?$Ä• ÄŽÄ‘$ÄŽ Ä?$Ä‘ Ä”$Ä“ Ä’$Ä’ Ä?$ÄŽ Ä?$Ä? ÄŽÄ‘$Ä’ ÄŽÄ?$Ä? ÄŽÄ‘$Ä? ÄŽÄ•$Ä–

@[`MX Ä’Ä”%Ä?Ĕĕ Ä’Ä?%Ä?Ä”Ä?

ÄŽÄ?Ä?$Ä?

-PMY_ Q` MX" ÄŽÄ–Ä•Ä“ .[^f[``M Q` MX" ÄŽÄ–Ä–Ä‘ /Q^^M Q` MX" ÄŽÄ–Ä–Ä• 0aZTMY Q` MX" ÄŽÄ–Ä–Ä‘ 4MPRUQXP Q` MX" ÄŽÄ–Ä–Ä’ 4MPXQe Q` MX" ÄŽÄ–Ä•Ä“ 7MXRM^QZ`f[_ Q` MX" ÄŽÄ–Ä–Ä” 7aP_W Q` MX" ÄŽÄ–Ä–Ä? 9[[^Q Q` MX" ÄŽÄ–Ä–Ä? >M\\ Q` MX" ÄŽÄ–Ä•Ä? C[[PO[OW Q` MX" Ä?Ä?Ä?ÄŽ E[aZS Q` MX" ÄŽÄ–Ä–Ä?

Ä?$ÄŽÄ?

Ä?$Ä?ÄŽ

2Mb[a^_ 1:

ÄŽÄ?Ä?

ÄŽÄ?

ÄŽ$Ä?Ä?

2Mb[a^_ <:

<: Z%: ÄŽ%Ä?Ä? ÄŽ%ÄŽÄ? Ä?%Ä•Ä” Ä?%Ä?Ä? ÄŽ%Ä?Ä‘ Ä–%ÄŽÄ• Ä?%Ä?Ä? Ä–%ÄŽÄ”

CQUST` Ä?$Ä‘ Ä?$Ä– Ä”$Ä“ ÄŽÄ?$Ä“ Ä’$Ä• Ä?ÄŽ$Ä’ Ä”$Ä” Ä?Ä–$Ä“

@[`MX Ä?Ä•%Ä?Ĕđ ÄŽÄ•%Ä?Ĕđ

ÄŽÄ?Ä?$Ä?

-PMY_ Q` MX" ÄŽÄ–Ä•Ä“ 0aZTMY Q` MX" ÄŽÄ–Ä–Ä‘ 3UMZ[``U Q` MX" ÄŽÄ–Ä–Ä” 7MXRM^QZ`f Q` MX" ÄŽÄ–Ä–Ä” 7aP_W Q` MX" ÄŽÄ–Ä–Ä‘ >M\\ Q` MX" ÄŽÄ–Ä•Ä? >QeZ[XP_ Q` MX" ÄŽÄ–Ä–Ä” C[[PO[OW Q` MX

1: Z%: Ä?%Ä?Ä? Ä?%ÄŽÄ“ Ä?%Ä•Ä” Ä?%Ä?Ä? Ä?%Ä?Ä‘ Ä?%Ä?Ä? ÄŽ%Ä?Ä‘ Ä’%Ä?ÄŽ

Ä?$Ä?ÄŽ

Ä?$ÄŽÄ? 2Mb[a^_ 1:

ÄŽ$Ä?Ä?

ÄŽÄ?

ÄŽÄ?Ä?

2Mb[a^_ <:

2US$ ÄŽ >Q_aX`_ [R `c[ ^QOQZ` YQ`M#MZMXe_Q_ [bQ^ _`aPUQ_ O[Y\M^UZS `TQ QRRQO` a\[Z Y[^`MXU`e [R QZ`Q^MX [^ \M^QZ`Q^MX Za`^U# `U[Z `[ 5/A \M`UQZ`_ G4QeXMZP Q` MX$ Ä?Ä?Ä?Ä?" ?UY\_[Z MZP 0[US Ä?Ä?Ä?Ä’I$ -_ OMZ NQ _QQZ" `TQ [bQ^XM\ UZ ^QbUQcQP _`aPUQ_ U_ O[Z_UPQ^MNXQ$ @TQ PURRQ^QZOQ UZ _QXQO`U[Z [R _`aPUQ_ OMa_Q_ `TQ PURRQ^QZOQ UZ ^Q_aX`_ GC[[PO[OW Q` MX$ Ä?Ä?Ä?ÄŽ" -PMY_ Q` MX$ ÄŽÄ–Ä•Ä“" .[^f[``M Q` MX$ ÄŽÄ–Ä–Ä‘" /Q^^M Q` MX$ ÄŽÄ–Ä•Ä•" 0aZTMY Q` MX$ ÄŽÄ–Ä–Ä‘" 3UMZ[``U Q` MX$ ÄŽÄ–Ä–Ä”" 4MP¤QXP Q` MX$ ÄŽÄ–Ä–Ä’" 7MX# RM^QZ`f[_ Q` MX$ ÄŽÄ–Ä–Ä”" 7aP_W Q` MX$ ÄŽÄ–Ä–Ä?" 9[[^Q Q` MX$ ÄŽÄ–Ä–Ä?" >M\\ Q` MX$ ÄŽÄ–Ä•Ä?" >QeZ[XP_ Q` MX$ ÄŽÄ–Ä–Ä”" E[aZS Q` MX$ ÄŽÄ–Ä•Ä”I$ 4QeXMZP Q` MX a\\Q^ \MZQX ¤ZP Z[ PURRQ^QZOQ" cTUXQ ?UY\_[Z MZP 0[US X[cQ^ \MZQX ¤ZP M X[cQ^ Y[^`MXU`e R[^ \M# `UQZ`_ [Z \M^QZ`Q^MX Za`^U`U[Z$

ground, and a further dimension to the difficulties in evaluating the existing evidence of parenteral versus enteral nutrition in the ICU. The best strategy for the future is definitely to watch for good routines in the unit, in this particu-

lar case to minimise the complications associated with parenteral as well as enteral administration of nutrients. Secondly, assuring that patients are fed properly from the start of their ICU stay.

7

-$ 3QZQ^MX UZ`QZ_UbQ OM^Q YQPUOUZQ

5/A Za`^U`U[Z Ä?Ä?Ä?Ä” Overall, the position of nutrition in the ICU today is an established treatment that many colleagues in intensive care medicine do not give very much emphasis. Still, it is highly likely that the outcome in the group of long-term patients in the ICU is highly dependent upon adequate nutrition. Results are emerging demonstrating that an accumulated energy deficit is to the clear disadvantage of the patient [Villet et al. 2005, Dvir et al. 2005, Reid and Campbell 2004]. Of course such results must be interpreted carefully, but also when multiple regression analysis compensates the differences in underlying pathology and risk stratification, the results pointing out a connection between underfeeding and complications and increased mortality remain. Studies of the cumulative energy deficit show that a large portion of it is created during the first week of ICU stay. Of course a short-term patient that will leave the ICU within a few days and commence eating ordinary food is not a big problem. On the other

hand, if a malnutriated patient comes to the unit and stays for several weeks, no feeding during the initial period may be detrimental. In the literature there is very little evidence that a circulatorily unstable patient will not utilise nutrition. In particular when such a patient is measured by indirect calorimetry, it is clearly demonstrated that oxygen is consumed and carbon dioxide produced, ergo macronutrients are being combusted. The route of nutrient administration may be discussed. A circulatorily compromised patient may not be a suitable candidate for enteral nutrition. Overall over-enthusiastic enteral supply may be to the harm of the patient. It has been clearly demonstrated that doctors frequently overestimate gut function [Woodcock et al. 2001]. So, parenteral nutrition in the initial phase of ICU stay may be necessary in many patients. Such a combination of enteral and parenteral nutrition, with today’s knowledge, is probably the best way to avoid an accumulated energy deficit. To obtain this target it is necessary to keep a nutritional record, where daily balances are recorded and action is taken on

Ä•Ä?

Y[^`MXU`e

Ä“Ä?

Z_ Z_

Ä‘Ä? Z_

Ä?Ä?

Z_ Z_ Z_

Ä? 4[aPUVW ÄŽÄ–Ä–Ä• 6[ZQ_ ÄŽÄ–Ä–Ä–

4MXX Ä?Ä?Ä?Ä?

3M^^QX Ä?Ä?Ä?Ä? /[ZQVQ^[ Ä?Ä?Ä?Ä? FT[a Ä?Ä?Ä?Ä?

2US$ Ä? 9[^`MXU`e ^M`Q_ UZ _`aPUQ_ [bQ^ 5/A \M`UQZ`_ ^MZP[YU_QP `[ NQ SUbQZ QZ`Q^MX Za`^U`U[Z _a\\XQYQZ`QP cU`T SXa`MYUZQ [^ Z[` G/[ZQVQ^[ Q` MX$ Ä?Ä?Ä?Ä?" 3M^^QX Q` MX$ Ä?Ä?Ä?Ä?" 4MXX Q` MX$ Ä?Ä?Ä?Ä?" 4[aPUVW MZP bMZ 8QQacQZ Ä?Ä?Ä?Ä?" 6[ZQ_ Q` MX$ ÄŽÄ–Ä–Ä–" FT[a Q` MX$ Ä?Ä?Ä?Ä?I$ @TQ PUMS^MY PQ\UO`_ `TQ cUPQ ^MZSQ [R Y[^`MXU`e ^M`Q_ ^QÂĽQO`UZS `TQ TQ`Q^[SQZQU`e [R \M`UQZ` \[\aXM`U[Z_ UZOXaPQP UZ `TQ PURRQ^QZ` _`aPUQ_$ @MWQZ `[SQ`TQ^ `TQ _`aPUQ_ [bQ^ QZ`Q^MX Za`^U`U[Z _a\\XQYQZ`QP cU`T SXa`MYUZQ M^Q `TQ^QR[^Q Z[` O[ZOXa_UbQ$

8

-

:a`^U`U[Z

the rounds to prevent under-nutrition. Ideally nurses should make these calculations each shift and the nutrition given should be adjusted accordingly. For special nutrients the addition of intravenous glutamine has sufficient evidence. So far this evidence is confined to patients on parenteral nutrition [Novak et al. 2002]. There are different interpretations of whether this effect is a treatment of a shortage or whether there is a specific effect linked to an extra supply of glutamine, a pharmaco-nutritional effect. In contrast to the results from studies of intravenously supplied glutamine, studies with enterally supplied glutamine are so far not conclusive. Some studies show a beneficial effect upon morbidity while others show no effect at all. In general these studies include patients with a good prognosis in terms of mortality (fig. 2), and it is not clear to what extent they actually represents subjects which are depleted in glutamine or have an elevated need for glutamine. So far, however, there are no studies demonstrating adverse effects related to glutamine supplementation. So, the safety issue is not a problem. The issue is rather whether or not a relatively expensive supplementation can be encouraged.

@TQ Ma`T[^ 6MZ CQ^ZQ^YMZ" 90" <T0 0Q\M^`YQZ` [R -ZQ_`TQ_UM MZP 5Z`QZ_UbQ /M^Q 9QPUOUZQ 7M^[XUZ_WM AZUbQ^_U`e 4[_\U`MX 4aPPUZSQ 7M^[XUZ_WM 5Z_`U`a`Q` ?`[OWT[XY" ?cQPQZ Q#YMUX& VMZ$cQ^ZQ^YMZ,WM^[XUZ_WM$_Q

>QRQ^QZOQ_ -PMY_ ?" 0QXXUZSQ^ 1<" CQ^`f 96" ;^Q_W[bUOT 9>" ?UY[Z[cU`f 0" 6[TMZ_QZ 7$ 1Z`Q^MX bQ^_a_ \M^QZ`Q^MX Za`^U`U[ZMX _a\# \[^` R[XX[cUZS XM\M^[`[Ye R[^ `^MaYM& M ^MZP[YUfQP \^[# _\QO`UbQ `^UMX$ 6 @^MaYM ĎĖĕē' ďē Ďč & ĕĕď ĖĎ$ .Q^S -" 2[^_NQ^S 1" CQ^ZQ^YMZ 6$ @TQ X[OMX bM_OaXM^ `[XQ^MZOQ `[ MZ UZ`^MbQZ[a_ UZRa_U[Z [R M O[ZOQZ`^M`QP SXa`MYUZQ _[Xa`U[Z UZ 5/A \M`UQZ`_$ /XUZ :a`^ ďččď' ďĎ ď & ĎĐĒ Ė$ bMZ PQZ .Q^STQ 3" C[a`Q^_ <" CQQWQ^_ 2" BQ^cMQ_` /" .^aeZ# UZOWd 2" ?OTQ`f 9" Q` MX$ 5Z`QZ_UbQ UZ_aXUZ `TQ^M\e UZ `TQ

O^U`UOMXXe UXX \M`UQZ`_$ : 1ZSX 6 9QP ďččĎ' ĐđĒ ĎĖ & ĎĐĒĖ ēĔ$ bMZ PQZ .Q^STQ 3" CUXYQ^ -" 4Q^YMZ_ 3" 9QQ^__QYMZ C" C[a`# Q^_ <6" 9UXMZ`_ 5" Q` MX$ 5Z`QZ_UbQ UZ_aXUZ `TQ^M\e UZ `TQ YQPUOMX 5/A$ : 1ZSX 6 9QP ďččē' ĐĒđ Ē & đđĖ ēĎ$ .Q^`[XUZU 3" 5M\UOTUZ[ 3" >MP^UffMZU 0" 2MOOTUZU >" ?UYUZU ." .^af# f[ZQ <" Q` MX$ 1M^Xe QZ`Q^MX UYYaZ[Za`^U`U[Z UZ \M`UQZ`_ cU`T _QbQ^Q _Q\_U_& ^Q_aX`_ [R MZ UZ`Q^UY MZMXe_U_ [R M ^MZ# P[YUfQP YaX`UOQZ`^Q OXUZUOMX `^UMX$ 5Z`QZ_UbQ /M^Q 9QP ďččĐ' ďĖ Ē & ĕĐđ đč$ .[^f[``M -<" <QZZUZS_ 6" <M\M_MPQ^[ ." <Md`[Z 6" 9M^PQ_UO ?" .[^f[` `M >" Q` MX$ 1Z`Q^MX bQ^_a_ \M^QZ`Q^MX Za`^U`U[Z MR`Q^ _QbQ^Q OX[_QP TQMP UZVa^e$ 6 @^MaYM ĎĖĖđ' ĐĔ Đ & đĒĖ ēĕ$ .[cQ^ >4" /Q^^M 2." .Q^_TMP_We ." 8UOM^U 66" 4[e` 0." 6QZ_QZ 38" Q` MX$ 1M^Xe QZ`Q^MX MPYUZU_`^M`U[Z [R M R[^YaXM 5Y\MO` _a\\XQYQZ`QP cU`T M^SUZUZQ" ZaOXQ[`UPQ_" MZP RU_T [UX UZ UZ`QZ_UbQ OM^Q aZU` \M`UQZ`_& ^Q_aX`_ [R M YaX`UOQZ`Q^" \^[# _\QO`UbQ" ^MZ P[YUfQP" OXUZUOMX `^UMX$ /^U` /M^Q 9QP ĎĖĖĒ' ďĐ Đ & đĐē đĖ$ /M^X__[Z 9" .a^SQ^YMZ >$ ;bQ^Q_`UYM`U[Z [R OMX[^UO PQYMZP UZ M X[ZS#`Q^Y O^U`UOMXXe UXX \M`UQZ`$ /XUZUOMX :a`^U`U[Z ĎĖĕĒ' đ& ĖĎ ĖĐ$ /Q^^M 2." 9O<TQ^_[Z 6<" 7[Z_`MZ`UZUPQ_ 2:" 7[Z_`MZ`UZUPQ_ ::" @QM_ XQe 79$ 1Z`Q^MX Za`^U`U[Z P[Q_ Z[` \^QbQZ` YaX`U\XQ [^SMZ RMUXa^Q _eZP^[YQ 9;2? MR`Q^ _Q\_U_$ ?a^SQ^e ĎĖĕĕ' Ďčđ đ & ĔďĔ ĐĐ$ /[ZQVQ^[ >" .[ZQ` -" 3^Ma @" 1_`QNMZ -" 9Q_QV[ -" 9[Z`QV[ 6/" Q` MX$ 1RRQO` [R M SXa`MYUZQ#QZ^UOTQP QZ`Q^MX PUQ` [Z UZ`Q_# `UZMX \Q^YQMNUXU`e MZP UZRQO`U[a_ Y[^NUPU`e M` ďĕ PMe_ UZ O^U`UOMXXe UXX \M`UQZ`_ cU`T _e_`QYUO UZRXMYYM`[^e ^Q_\[Z_Q _eZP^[YQ& M ^MZP[YUfQP" _UZSXQ#NXUZP" \^[_\QO`UbQ" YaX`U# OQZ`Q^ _`aPe$ :a`^U`U[Z ďččď' Ďĕ Ė & ĔĎē ďĎ$ 0QZ` 08" 4QeXMZP 07" 8Qbe 4$ 5YYaZ[Za`^U`U[Z YMe UZO^QM_Q Y[^`MXU`e UZ \M`UQZ`_ cU`T \ZQaY[ZUM$ >Q_aX`_ R M ^MZP# [YUfQP `^MUX$ /^U`UOMX /M^Q 9QPUOUZQ ďččĐ' Đč& -ĎĔ$ 0aZTMY /9" 2^MZWQZRUQXP 0" .QXfNQ^S 4" CUXQ_ /" /a_TUZS ." 3^MZ` F$ 3a` RMUXa^Q##\^QPUO`[^ [R [^ O[Z`^UNa`[^ `[ Y[^`MX# U`e UZ YQOTMZUOMXXe bQZ`UXM`QP NXaZ` `^MaYM \M`UQZ`_+ 6 @^MaYM ĎĖĖđ' ĐĔ Ď & Đč đ$ 0bU^ 0" /[TQZ 6" ?UZSQ^ <$ /[Y\a`Q^UfQP QZQ^Se NMXMZOQ MZP O[Y\XUOM`U[Z_ UZ O^U`UOMXXe UXX \M`UQZ`_& -Z [N_Q^bM`U[ZMX _`aPe$ /XUZ :a`^ ďččĒ$ 3MPQW 61" 0Q9UOTQXQ ?6" 7M^X_`MP 90" <MOT` 1>" 0[ZMT[Q 9" -XNQ^`_[Z @1" Q` MX$ 1RRQO` [R QZ`Q^MX RQQPUZS cU`T QUO[_M\# QZ`MQZ[UO MOUP" SMYYM#XUZ[XQZUO MOUP" MZP MZ`U[dUPMZ`_ UZ \M`UQZ`_ cU`T MOa`Q ^Q_\U^M`[^e PU_`^Q__ _eZP^[YQ$ 1Z`Q^MX :a`^U`U[Z UZ ->0? ?`aPe 3^[a\$ /^U` /M^Q 9QP ĎĖĖĖ' ďĔ ĕ & ĎđčĖ ďč$ 3M^^QX 0" <M`QZMaPQ 6" :QPQXQO ." ?MY_[Z 8" 0[^MU_ 6" /TMY\[ad 6" Q` MX$ 0QO^QM_QP Y[^`MXU`e MZP UZRQO`U[a_ Y[^NUPU`e UZ MPaX` Na^Z \M`UQZ`_ SUbQZ QZ`Q^MX SXa`MYUZQ _a\\XQYQZ`_& M \^[_\QO`UbQ" O[Z`^[XXQP" ^MZP[YUfQP OXUZUOMX `^UMX$ /^U` /M^Q 9QP ďččĐ' ĐĎ Ďč & ďđđđ Ė$ 3UMZ[``U 8" .^MSM 9" BUSZMXU -" .MXfMZ[ 3" FQ^NU -" .U_MSZU <" Q` MX$ 1RRQO` [R ^[a`Q [R PQXUbQ^e MZP R[^YaXM`U[Z [R \[_`[\#

9

-$ 3QZQ^MX UZ`QZ_UbQ OM^Q YQPUOUZQ

Q^M`UbQ Za`^U`U[ZMX _a\\[^` UZ \M`UQZ`_ aZPQ^S[UZS YMV[^ [\Q^M`U[Z_ R[^ YMXUSZMZ` ZQ[\XM_Y_$ -^OT ?a^S ĎĖĖĔ' ĎĐď ĎĎ & Ďďďď Ė' PU_Oa__U[Z ĎďďĖ Đč$ 3[Q`Q^_ /" CQZZ -" 9Q^`Q_ :" CQY\Q /" BMZ -WQZ 4" ?`QTXQ <" Q` MX$ <M^QZ`Q^MX 8#MXMZeX#8#SXa`MYUZQ UY\^[bQ_ ē#Y[Z`T [a`O[YQ UZ O^U`UOMXXe UXX \M`UQZ`_$ /^U` /M^Q 9QP ďččď' Đč Ė & ďčĐď Ĕ$ 3^URRU`T_ >0" 6[ZQ_ /" <MXYQ^ @1$ ?Ud#Y[Z`T [a`O[YQ [R O^U`U# OMXXe UXX \M`UQZ`_ SUbQZ SXa`MYUZQ#_a\\XQYQZ`QP \M^QZ`Q^# MX Za`^U`U[Z$ :a`^U`U[Z ĎĖĖĔ' ĎĐ đ & ďĖĒ Đčď$ 4MPRUQXP >6" ?UZOXMU^ 03" 4[aXP_c[^`T <1" 1bMZ_ @C$ 1RRQO`_ [R QZ`Q^MX MZP \M^QZ`Q^MX Za`^U`U[Z [Z Sa` YaO[_MX \Q^YQM# NUXU`e UZ `TQ O^U`UOMXXe UXX$ -Y 6 >Q_\U^ /^U` /M^Q 9QP ĎĖĖĒ' ĎĒď Ē <` Ď & ĎĒđĒ ĕ$ 4MXX 6/" 0[NN 3" 4MXX 6" PQ ?[a_M >" .^QZZMZ 8" 9O/MaXQe >$ - \^[_\QO`UbQ ^MZP[YUfQP `^UMX [R QZ`Q^MX SXa`MYUZQ UZ O^U`U# OMX UXXZQ__$ 5Z`QZ_UbQ /M^Q 9QP ďččĐ' ďĖ& ĎĔĎč ĎĔĎē$ 4MYYM^_WV[XP 2" CMXXQZ 3" 9MXYbMXX .1$ /QZ`^MX bQZ[a_ OM`T# Q`Q^ UZRQO`U[Z_ M` M O[aZ`e T[_\U`MX UZ ?cQPQZ& M \^[_\QO# `UbQ MZMXe_U_ [R O[X[ZUfM`U[Z" UZOUPQZOQ [R UZRQO`U[Z MZP ^U_W RMO`[^_$ -O`M -ZMQ_`TQ_U[X ?OMZP ďččē' Ēč đ & đĒĎ ēč$ 4QeXMZP 07" 0TMXUcMX >" 0^[bQ^ 6C" 3^MYXUOT 8" 0[PQW <$ /MZM# PUMZ OXUZUOMX \^MO`UOQ SaUPQXUZQ_ R[^ Za`^U`U[Z _a\\[^` UZ YQOTMZUOMXXe bQZ`UXM`QP" O^U`UOMXXe UXX MPaX` \M`UQZ`_$ 6<1: 6 <M^QZ`Q^ 1Z`Q^MX :a`^ ďččĐ' ďĔ Ē & ĐĒĒ ĔĐ$ 4QeXMZP 07" ?MYU_ -$ 0[Q_ UYYaZ[Za`^U`U[Z UZ \M`UQZ`_ cU`T _Q\_U_ P[ Y[^Q TM^Y `TMZ S[[P+ 5Z`QZ_UbQ /M^Q 9QP ďččĐ' ďĖ Ē & ēēĖ ĔĎ$ 4[aPUVW -<" bMZ 8QQacQZ <-$ 3Xa`MYUZQ#QZ^UOTQP QZ`Q^MX Za`^U# `U[Z UZ YaX`U\XQ `^MaYM \M`UQZ`_$ :a`^U`U[Z ďččč' Ďē Ď & Ĕč Ď$ 6[ZQ_ /" <MXYQ^ @1" 3^URRU`T_ >0$ >MZP[YUfQP OXUZUOMX [a`O[YQ _`aPe [R O^U`UOMXXe UXX \M`UQZ`_ SUbQZ SXa`MYUZQ#_a\\XQYQZ`# QP QZ`Q^MX Za`^U`U[Z$ :a`^U`U[Z ĎĖĖĖ' ĎĒ ď & Ďčĕ ĎĒ$ 7MXRM^QZ`f[_ 2" 7QTMSUM_ 6" 9QMP :" 7[WWUZU_ 7" 3[S[_ /-$ 1Z# `Q^MX Za`^U`U[Z U_ _a\Q^U[^ `[ \M^QZ`Q^MX Za`^U`U[Z UZ _QbQ^Q MOa`Q \MZO^QM`U`U_& ^Q_aX`_ [R M ^MZP[YUfQP \^[_\QO`UbQ `^UMX$ .^ 6 ?a^S ĎĖĖĔ' ĕđ Ďď & ĎēēĒ Ė$ 7aP_W 7-" /^[OQ 9-" 2MNUMZ @/" 9UZM^P 3" @[XXQe 1-" <[^Q` 4-" Q` MX$ 1Z`Q^MX bQ^_a_ \M^QZ`Q^MX RQQPUZS$ 1RRQO`_ [Z _Q\`UO Y[^NUPU`e MR`Q^ NXaZ` MZP \QZQ`^M`UZS MNP[YUZMX `^MaYM$ -ZZ ?a^S ĎĖĖď' ďĎĒ Ē & ĒčĐ ĎĎ' PU_Oa__U[Z ĒĎĎ Đ$ 9[[^Q 2-" 2QXUOUMZ[ 0B" -ZP^M__e >6" 9O-^PXQ -4" .[[`T 2B" 9[^SQZ_`QUZ#CMSZQ^ @." Q` MX$ 1M^Xe QZ`Q^MX RQQPUZS" O[Y# \M^QP cU`T \M^QZ`Q^MX" ^QPaOQ_ \[_`[\Q^M`UbQ _Q\`UO O[Y# \XUOM`U[Z_$ @TQ ^Q_aX`_ [R M YQ`M#MZMXe_U_$ -ZZ ?a^S ĎĖĖď' ďĎē ď & ĎĔď ĕĐ$ 9aZ^[ 4:" -XXU_[Z 6.$ 9MYYMXUMZ <^[`QUZ 9Q`MN[XU_Y 5$ .U[# OTQYUOMX M_\QO`_ [R \^[`QUZ YQ`MN[XU_Y$ :Qc E[^W MZP 8[ZP[Z& -OMPQYUO <^Q__ ĎĖēĐ$

10

:[bMW 2" 4QeXMZP 07" -bQZQXX -" 0^[bQ^ 6C" ?a D$ 3Xa`MYUZQ _a\\XQYQZ`M`U[Z UZ _Q^U[a_ UXXZQ__& M _e_`QYM`UO ^QbUQc [R `TQ QbUPQZOQ$ /^U` /M^Q 9QP ďččď' Đč Ė & ďčďď Ė$ ;aPQYMZ_#bMZ ?`^MM`QZ 49" .[_YMZ >6" @^Q_WQ_ 9" bMZ PQ^ ?\[QX 46" FMZP_`^M 02$ <XM_YM SXa`MYUZQ PQ\XQ`U[Z MZP \M`UQZ` [a`O[YQ UZ MOa`Q 5/A MPYU__U[Z_$ 5Z`QZ_UbQ /M^Q 9QP ďččĎ' ďĔ Ď & ĕđ Ėč$ <[Z`Q_#-^^aPM -" -^MSM[ -9" -XNa]aQ^]aQ 60$ 1RRQO`_ [R QZ`Q^MX RQQPUZS cU`T QUO[_M\QZ`MQZ[UO MOUP" SMYYM#XUZ[XQZUO MOUP" MZP MZ`U[dUPMZ`_ UZ YQOTMZUOMXXe bQZ`UXM`QP \M`UQZ`_ cU`T _QbQ^Q _Q\_U_ MZP _Q\`UO _T[OW$ /^U` /M^Q 9QP ďččē' Đđ Ė & ďĐďĒ ĐĐ$ >M\\ ><" E[aZS ." @ceYMZ 0" .UbUZ_ .-" 4MMOW 0" @UNN_ <-" Q` MX$ @TQ RMb[^MNXQ QRRQO` [R QM^Xe \M^QZ`Q^MX RQQPUZS [Z _a^# bUbMX UZ TQMP#UZVa^QP \M`UQZ`_$ 6 :Qa^[_a^S ĎĖĕĐ' Ēĕ ē & Ėčē Ďď$ >QUP /8" /MY\NQXX 5@$ 4e\[OMX[^UO Za`^U`U[ZMX _a\\[^` U_ Z[` M_# _[OUM`QP cU`T UZO^QM_QP ^M`Q_ [R Ya_OXQ cM_`UZS [^ ZQSM# `UbQ ZU`^[SQZ NMXMZOQ UZ O^U`UOMX UXXZQ__ Na` U_ M__[OUM`QP cU`T UZO^QM_QP Y[^`MXU`e$ /XUZUOMX :a`^U`U[Z ďččđ' ďĐ& ĕĒď$ >QeZ[XP_ 6B" 7MZcM^ ?" CQX_T 27" CUZP_[^ -/" 9a^OTMZ <" .M^# OXMe 3>" Q` MX$ ĎĖĖĔ 4M^^e 9$ BM^_ >Q_QM^OT -cM^P$ 0[Q_ `TQ ^[a`Q [R RQQPUZS Y[PURe Sa` NM^^UQ^ RaZO`U[Z MZP OXUZUOMX [a`O[YQ UZ \M`UQZ`_ MR`Q^ YMV[^ a\\Q^ SM_`^[UZ`Q_`UZMX _a^# SQ^e+ 6<1: 6 <M^QZ`Q^ 1Z`Q^MX :a`^ ĎĖĖĔ' ďĎ đ & ĎĖē ďčĎ$ ?UY\_[Z 2" 0[US 3?$ <M^QZ`Q^MX b_$ QZ`Q^MX Za`^U`U[Z UZ `TQ O^U`# UOMXXe UXX \M`UQZ`& M YQ`M#MZMXe_U_ [R `^UMX_ a_UZS `TQ UZ`QZ# `U[Z `[ `^QM` \^UZOU\XQ$ 5Z`QZ_UbQ /M^Q 9QP ďččĒ' ĐĎ Ď & Ďď ďĐ$ ?UZSQ^ <" @TQUXXM 9" 2U_TQ^ 4" 3UN_`QUZ 8" 3^[f[b_WU 1" /[TQZ 6$ .QZQRU` [R MZ QZ`Q^MX PUQ` QZ^UOTQP cU`T QUO[_M\QZ`MQZ[UO MOUP MZP SMYYM#XUZ[XQZUO MOUP UZ bQZ`UXM`QP \M`UQZ`_ cU`T MOa`Q XaZS UZVa^e$ /^U` /M^Q 9QP ďččē' Đđ đ & ĎčĐĐ ĕ$ BUXXQ` ?" /TU[XQ^[ >8" .[XXYMZZ 90" >QbQXXe 6<" /MeQad >:9" 0QXM^aQ 6" Q` MX$ :QSM`UbQ UY\MO` [R Te\[OMX[^UO RQQPUZS MZP QZQ^Se NMXMZOQ [Z OXUZUOMX [a`O[YQ UZ 5/A \M`UQZ`_$ /XUZ :a`^ ďččĒ' ďđ đ & Ēčď Ė$ CUXY[^Q 0C$ @TQ 9Q`MN[XUO 9MZMSQYQZ` [R `TQ /^U`UOMXXe 5XX$ :Qc E[^W MZP 8[ZP[Z& <XQZaY 9QPUOMX .[[W_ /[Y\MZe ĎĖĔĔ$ C[[PO[OW :<" FQUSXQ^ 0" <MXYQ^ 90" .aOWXQe <" 9U`OTQXX /6" 9MO# 2UQ 6$ 1Z`Q^MX bQ^_a_ \M^QZ`Q^MX Za`^U`U[Z& M \^MSYM`UO _`aPe$ :a`^U`U[Z ďččĎ' ĎĔ Ď & Ď Ďď$ E[aZS ." ;`` 8" @ceYMZ 0" :[^`[Z 6" >M\\ >" @UNN_ <" Q` MX$ @TQ QRRQO` [R Za`^U`U[ZMX _a\\[^` [Z [a`O[YQ R^[Y _QbQ^Q TQMP UZVa^e$ 6 :Qa^[_a^S ĎĖĕĔ' ēĔ Ē & ēēĕ Ĕē$ FT[a E<" 6UMZS F9" ?aZ E4" CMZS D>" 9M 18" CUXY[^Q 0$ @TQ QRRQO` [R _a\\XQYQZ`MX QZ`Q^MX SXa`MYUZQ [Z \XM_YM XQbQX_" Sa` RaZO`U[Z" MZP [a`O[YQ UZ _QbQ^Q Na^Z_& M ^MZP[YUfQP" P[aNXQ#NXUZP" O[Z`^[XXQP OXUZUOMX `^UMX$ 6<1: 6 <M^QZ`Q^ 1Z# `Q^MX :a`^ ďččĐ' ďĔ đ & ďđĎ Ē$

>$ 9UOTMQX 3^[aZP_ MZP >UOTM^P 9$ BQZZ

?QPM`U[Z MZP MZMXSQ_UM UZ 5/A

5Z`^[PaO`U[Z 9MZe \M`UQZ`_ UZ `TQ UZ`QZ_UbQ OM^Q aZU` 5/A cUXX ^Q]aU^Q _[YQ R[^Y [R _QPM`U[Z [^ MZMXSQ_UM" \M^`UOaXM^Xe `T[_Q cT[ ^Q]aU^Q YQOTMZUOMX bQZ`UXM`U[Z [^ `T[_Q cT[ TMbQ Va_` aZPQ^S[ZQ _a^SQ^e$ ?QPM`U[Z O[YQ_ R^[Y `TQ 8M`UZ c[^P _QPM^Q YQMZUZS `[ _[[`T `[ OMXY [^ `[ MXXMe RQM^$ @Ta_ `TQ \^UZOU\MX MUY_ [R _QPM`U[Z M^Q" cTQ^Q M\\^[\^U# M`Q" `[ UY\^[bQ \M`UQZ` O[YR[^`" ^QPaOQ \M`UQZ` _`^Q__" RMOUXU`M`Q UZ`Q^bQZ`U[Z_" MXX[c QRRQO`UbQ YQOTMZUOMX bQZ# `UXM`U[Z" QZO[a^MSQ _XQQ\ MZP \[__UNXe TQX\ `[ \^QbQZ` \[_`#5/A \_eOT[X[SUOMX \^[NXQY_ @TQ YMZe UZRXaQZOQ_ UZ `TQ 5/A MRRQO`UZS `TQ cQXX# NQUZS [R `TQ \M`UQZ` MZP `TQ bM^U[a_ Z[Z#\TM^YMO[X[SUOMX MZP \TM^YMO[X[SUOMX YQM_a^Q_ a`UXU_QP `[ YUZUYU_Q `TQU^ UY\MO` M^Q PQY[Z_`^M`QP UZ RUSa^Q ÄŽ$

5ZPUOM`U[Z_ MZP ZQQP R[^ _QPM`U[Z%MZMXSQ_UM <M`UQZ` O[YR[^` MZP \_eOT[X[Se%MZdU[Xe_U_ It is essential to provide some sort of anxiolysis for the patient who is now no longer in control of their own breathing and is fearful of the disease and the frequently busy and noisy ICU environment. Survivors of intensive care have reported distressing memories and anxiety, fear, pain and the presence of various catheters and

procedures such as physiotherapy and airway suction [ Jones et al. 1979, Stein-Parbury and Mckinley 2000].

-ZMXSQ_UM Patients in intensive care frequently experience pain or discomfort. Failure by carers to recognise that the patient may be experiencing pain, may result in the patient receiving unnecessary sedatives, since pain may show as agitation or anxiety. Usually the source of pain is self evident: post-operative, procedural (e.g. physiotherapy, dressing change, bronchoscopy) or premorbid disease (e.g. rheumatoid arthritis). However prolonged immobility, urinary catheters, surgical drains, non-invasive ventilation, and airway suctioning, may also cause discomfort [Novaes et al. 1999, Desbiens et al. 1996, Stein-Parbury and Mckinley 2000]. Pain is usually associated with sympathetic hyperactivity with increases in heart rate, arterial pressure, and myocardial oxygen consumption and may lead to myocardial ischaemia in those already at risk [Epstein and Breslow 1999, Mangano et al. 1992]. Pain may also be the cause of post operative atelectasis due to guarding and reduced or restricted chest wall and diaphragmatic movement [Desai 1999, Gust et al. 1999].

11

-$ 3QZQ^MX UZ`QZ_UbQ OM^Q YQPUOUZQ

:[Z#\TM^YMO[X[SUOMX UZ`Q^bQZ`U[Z

<M`UQZ` \_eOTQ 2QM^ [R UXXZQ__ 0Q\^Q__U[Z%MZdUQ`e 8[__ [R O[Z`^[X

3[[P Za^_UZS <_eOT[X[SUOMX 1d\XMZM`U[Z

1ZbU^[ZYQZ` 5/A PQ_USZ # XUST`UZS 5/A MO`UbU`e # Z[U_Q

<Te_UOMX

0QXU^UaY MZP _XQQ\ PU_`a^NMZOQ_ ?XQQ\ PQ\^UbM`U[Z 5/A PQXU^UaY /U^OMPUMZ ^Te`TY

>QM__a^MZOQ 1ZO[a^MSQYQZ`

<-@51:@

<MUZ%PU_O[YR[^` <[_` [\Q^M`UbQ 5YY[NUXU`e <^[OQPa^Q_ Q$S$ \[_` _a^SQ^e" bQZ`UXM`U[Z 5Z_Q^`U[Z [R XUZQ_" \Te_U[`TQ^M\e" MU^cMe _aO`U[Z ?`^Q__ ^Q_\[Z_Q_ /M^PU[bM_OaXM^ :Qa^[QZP[O^UZQ 5ZRXMYYM`[^e

/TMZSQ QZbU^[ZYQZ` @[aOTUZS%YM__MSQ :a^_UZS \^QbQZ`UZS NQP#_[^Q_" O[Z_`U\M`U[Z Q`O <Te_U[`TQ^M\e Q$S$ \M__UbQ V[UZ` Y[bQYQZ`_

<TM^YMO[X[SUOMX UZ`Q^bQZ`U[Z -ZMXSQ_UM ;\U[UP_%[\UM`Q_

8[OMX MZMQ_`TQ`UO_ :?-50_ WQ`MYUZQ

@^MZ]aUXXU_Q^_ .QZf[PUMfQ\UZQ_

<TQZ[`TUM_UZQ_$ .a`e^[\TQZ[ZQ_

-ZMQ_`TQ`UO_%Te\Z[`UO_

<^[\[R[X -X\TM ď MS[ZU_`_ .M^NU`a^M`Q_ 7Q`MYUZQ /TX[^YQ`TUMf[XQ B[XM`UXQ MZMQ_`TQ`UO MSQZ`_

;`TQ^_ -Z`UPQ\^Q__MZ`_ -Z`U\_eOT[`UO_ 2US$ Ď 0UMS^MYYM`UO ^Q\^Q_QZ`M`U[Z [R RMO`[^_ MRRQO`UZS \M`UQZ`_ UZ 5/A MZP `TQ \[__UNXQ UZ`Q^bQZ`U[Z `[ UY\^[bQ `TQU^ O[YR[^`$

?XQQ\ PQ\^UbM`U[Z All critically ill patients suffer from severe sleep deprivation, averaging approximately only two of every 24 hours, with only 6 % of sleep time in REM sleep (normal 25 %) [Cooper et al. 2000, Freedman et al. 2001]. The aetiology of sleep disruption is not entirely understood but is clearly related to the environment (excessive noise, lighting, procedures and mechanical ventilation), metabolic consequences of critical illness and, disturbingly, the sedative and analgesic agents utilised [Bently et al. 1977, Freedman et al. 1999, Gabor et al. 2003, Pandharipande and Ely 2006]. Although sedatives are extremely important for patient comfort, it is very important that the prescriber achieves the correct balance since unnec-

12

essary sedation may contribute to sleep deprivation.

-``QZaM`U[Z [R `TQ _`^Q__ ^Q_\[Z_Q The benefits of effective analgesia on the cardiovascular stress responses have been discussed. The extubation period, when the patient is weaned from mechanical ventilation to spontaneous respiration and the endotracheal tube is removed, is a prime example of a situation where continuing sedation can attenuate the cardiovascular stress response that presents as tachycardia and hypertension, with potential myocardial ischaemia. Conti et al have shown that these haemodynamic disturbances and ischaemic events are attenuated

Turn static files into dynamic content formats.

Create a flipbook
Issuu converts static files into: digital portfolios, online yearbooks, online catalogs, digital photo albums and more. Sign up and create your flipbook.