Obtaining Nutrition In Intensive Care Biology Essay

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Gastroparesis, in addition known as deferred gastric emptying, gastric stasis, "slow stomach," gastroparesis diabeticorum, diabetic gastropathy or enteropathy, is potentially very devastating. It can wax as well as wane depending on the underlying aetiology. However, once a patient develops it, it does not necessarily development to an "end-stage" condition requiring nutrition support for life. To the contrary, several intractable patients, who at some point require jejuna feeding tube placement for nutrition hold up, eventually eat again on their own. Even though pro-kinetic agents plus antiemetic are front line therapy in the treatment of gastroparesis, the rationale of this piece of work is to offer strategies to maintain or restore nutritional status. (Fontana et al., 1996)

 Upper Gastrointestinal Motor Dysfunction in Critical Sickness:

Deferred gastric emptying is common in the Intensive Care Unit, occurring in approximately 50% of mechanically ventilated critically sick patients. In these patients both fasting in addition to fed motility of the upper GI tract are frequently harmed. There is a virtual absence of gastric phase 3 motility during the fasting state, even though the occurrence of phase 3 activity in the duodenum appears normal perhaps reflecting a loss of integration inside the antropyloroduodenal unit. Throughout feeding, however, a number of additional abnormalities turn out to be apparent. These comprise deferred fundal relaxation, prolonged recovery, reduced antral motility as well as augmented isolated pyloric activity. These occur when the small intestine is exposed to even low levels of nutrients moreover are likely to result in deferred gastric emptying. Thus deferred gastric emptying might reflect hypersensitivity to small intestinal nutrient. In contrast to deferred fundal relaxation plus impaired antral motility, duodenal activity usually persists moreover might describe why, in the absence of pro-kinetics, post pyloric feeding might potentially be further successful than gastric enteral nutrition. (Hasler, 1999)

The mechanisms underlying motor dysfunction in critical sickness are uncertain. However, concentrations of CCK in addition to PYY, which normally augment when nutrient reaches the small intestine in health, are markedly augmented in critical sickness especially in those intolerant of enteral feeding. It is, therefore, possible that CCK as well as PYY might mediate the enhanced entero-gastric impulse described above. (Shea et al., 2002)

Provocative cells in the intestinal wall contribute to motility disturbances after surgery. Surgical manipulation of the small intestine activates macrophages to release cytokines plus cause an additional leukocyte response in the muscular is external. In murine models this has been suggested to contribute to delay gastric emptying. However, while inflammation as of a local insult has been shown to cause altered motility in the post-operative setting, the impact of inflammation as of systemic non-operative insults is unknown. The effect of inflammation on motility in critical sickness warrants further investigation. (Jacober et al., 1986)

 Risk Factors for feed intolerance:

The aetiology of upper gastrointestinal motor dysfunction in critical sickness is unclear, however is probably multi-factorial. Potential factors implicated comprise the admission diagnosis, pre-existing sicknesses, electrolyte abnormalities (such as hyperglycaemia), age, gender, drugs (such as narcotics or catecholamine), recent abdominal surgery, and shock, along with circulating cytokines. Sickness severity, quantified as an APACHE 2 score in addition correlates by means of deferred gastric emptying. (Weber et al., 1993)

 Admission diagnosis

Gastric emptying data suggest that there are high risk groups for feed intolerance. These comprise patients by means of burns, head injuries, sepsis in addition to multi-trauma. However, patients by means of burns who are fed early moreover aggressively have a low incidence of feed intolerance implying that earlier feeding is protective. (Parrish et al., 2003)


Pre-morbid conditions

Patients by means of pre-morbid disordered glucose metabolism are frequently admitted to the ICU plus deferred gastric emptying occurs commonly by means of diseases such as diabetes mellitus. However, critically sick patients by means of pre-existing "type 2" diabetes appear to have normal or even rapid gastric emptying of liquid nutrient compared to non-diabetics. Faster emptying in diabetics might initially appear counter intuitive, however in non-critically sick diabetic patients, gastric emptying of liquid nutrient is in addition quicker when compared to volunteers devoid of diabetes. This is in direct contrast by means of the delay in gastric emptying of solid or semi-solid meals, in diabetics. As previously mentioned the proximal stomach contributes to normal gastric emptying. Critically sick patients devoid of diabetes have impairment of proximal gastric relaxation leading to deferred emptying. However, in the critically sick patient by means of pre morbid "type 2" diabetes, the proximal stomach relaxes, distends as well as accommodates a larger volume during infusion of duodenal nutrition, which is a response that mirrors what occurs in normal healthy physiology. In addition, critically sick diabetic patients have preservation of fundal waves while the non diabetic critically patients have decreased occurrence of isolated waves in the fundus. Fundal waves might aid progression of nutrient in critical sickness. The exact mechanism causing this "pseudo normalization" of gastric motility in addition to gastric emptying is unknown, however might be related to autonomic neuropathy in the diabetic patient, potentially causing a loss of the enhanced enteric feedback process that is common to critical sickness. (Parrish et al., 2003)

Increasing age has been associated by means of a slowing of gastric emptying in healthy volunteers. As ICU patients are, in general, older than the non-hospitalised population, it would be anticipated that age might contribute to the delay in gastric emptying seen in critical sickness. Elderly critically sick patients are at augmented risk of deferred emptying compared to younger patients. Gender has in addition been reported to impact on gastric emptying in health, by means of women having slower emptying rates compared to men, even though this association, unlike age, does not seem to apply in the critically sick. (Devendra et al., 2000)

 Electrolyte abnormalities

Hyperglycaemia occurs frequently in critically sick patients, even in patients by means of normal baseline glucose homeostasis. In health, hyperglycaemia impairs gastrointestinal motility along with gastric emptying, so it follows that the critically sick in addition have an association flanked by hyperglycaemia plus deferred gastric emptying, by means of a subsequent effect on feed intolerance. As discussed previously, eugylcaemic diabetic patients do not have an augmented incidence of deferred gastric emptying along with feed intolerance. (Parrish et al., 2003)


Several drugs worn in the critically sick can potentially influence gastrointestinal motility. Of particular concern are sedatives, analgesics as well as vasopressor agents. Both endogenous along with administered opiates, acting via mu receptors, might disrupt upper gastrointestinal motility. The impact of opiates, on the gastrointestinal tract, is due to both central effects plus peripheral opioid receptors located in the gut. Low dose epidural morphine delays gastric emptying and causes disordered motility implying a central effect is significant. The effect of receptor agonism is additive when both spinal along with parenteral morphine are administered together. Opiates slow gastric emptying as a result of decreased gastric tone in addition to antral contractions by means of retrograde duodenal activity. Even though opiates have been associated by means of deferred gastric emptying in the critically sick similar abnormalities have in addition been observed in critically sick patients not receiving exogenous narcotics; using propofol as a sedative in the critically sick is considered by clinicians to cause less slowing of gastrointestinal function; this belief is based on studies in healthy people; where low doses of propofol appear to have limited effects on gastric emptying in healthy humans plus for the reason that using propofol in blend by means of morphine attenuates the decrease in gastric tone usually seen when the opiate is worn as a single agent. However, the evidence is far as of conclusive. While propofol improved gastric tone during morphine administration, it had no effect on actual gastric emptying as well as in animal models propofol prolonged phase 1 motility during fasting in pigs. The effects of propofol on gastrointestinal motor function might be dose related as the drug, at anaesthetic doses, reduces gastric emptying moreover augments intestinal transit time in mice. In humans it remains difficult to accurately compare sedative agents in critically sick patients, as intensivists have usually avoided a propofol based sedative regime in the further acutely sick population for the reason that of concerns by means of hypotension in addition to the likelihood of prolonged sedative employ. No prospective comparison of propofol plus morphine, adjusted for sickness severity, has confirmed superiority of propofol on gastric emptying. In addition, propofol has been associated by means of feed intolerance in head injured patients moreover it might be prudent to avoid a dogmatic belief in the benefits of propofol for feeding tolerance. Midazolam, a benzodiazepine frequently prescribed by means of an opiate as a blend sedative in the ICU, in addition reduces gastric emptying along with prolongs gastrointestinal transit. (Shea et al., 2002)

High concentrations of circulating catecholamine, either endogenous or exogenous, are common in critically sick patients. Adrenaline reduces gastric emptying by a beta-adrenergic effect. This is likely to be a class effect, as low dose dopamine compared to placebo adversely affects gastro duodenal motility in the critically sick. In addition, high dose catecholamine has been associated by means of a reduction in the pro-kinetic effect of erythromycin. (Parrish et al., 2003)

 Feed Intolerance along with deferred gastric emptying:

Gastric emptying is rarely directly measured in the critically sick other than for research purposes. Regular measurement of gastric residual volume (GRV) during the infusion of enteral nutrition has been considered a convenient clinical tool by several clinicians plus is worn as a surrogate to indicate gastric emptying, success of feeding as well as potential risk of aspiration. Despite acceptance of GRV in feeding protocols by the majority of ICUs, the utility in addition to significance of this measurement is controversial as it is dependent on a number of factors. These comprise the position of the tube, tube characteristics, the volume of syringe worn along with the operator performing the test. GRV is usually performed every 4-6 h moreover, unlike the continuous monitoring of other end organ function, the significance of a 'snap shot' or a one off value might be hard to interpret. In addition, the relationship flanked by GRV plus gastric emptying is weak. These factors have lead to a lack of consensus on an acceptable value for GRV during enteral feeding. Computer simulated modelling suggests that GRV have to plateau flanked by 232 as well as 464 ml during enteral feeding at a rate of 25-125 mL/h. Currently the majority of intensive care units have protocols for feeding that consider a change in delivery rate or site if the GRV is flanked by 150-400 mL/s. The evidence for this is limited; as 25% of patients by means of a GRV > 150 mL have normal gastric emptying moreover can continue to be fed successfully devoid of pro-kinetics. In addition, moreover of further significance clinically, is that the high rate of aspiration in addition to oesophageal regurgitation observed in these patients is independent of GRV. As the current clinical significance of GRV is uncertain a convenient, continuous plus further reliable test of gastric emptying would assist in the nutritional management of these patients. (Parrish et al., 2003)

 Obtainable options for treatment:

Failure of delivery of nasogastric nutrition is usually managed either by pharmacological intervention or a change in the route of delivery of feeding. Various pro-kinetic agents are obtainable however few, to date, have been studied in depth in critically sick patients. (Parrish et al., 2003)



Metoclopramide is a dopamine receptor antagonist by means of central as well as peripheral effects, as well as weak 5-HT3 receptor antagonism along with 5-HT4 agonism. The drug releases acetylcholine as of gut neurones, antagonising the inhibitory effect of dopamine on gastrointestinal motility. Shea et al., (2002) demonstrated that metoclopramide improved gastric emptying in critically sick patients. However, recent data have shown that in critically sick patients rapid tachyphylaxis occurs, such that at 7 d, only 25% of patients given metoclopramide will continue to be fed successfully. The recommended dose of metoclopramide is 10 mg TDS or QID as there is limited evidence of improved efficacy at higher doses in the critically sick. Devoid of supporting evidence it remains prudent to limit the dose administered in the non-research setting for the reason that of the neurological side effect outline of the drug. Metoclopramide is ineffective as a pro-kinetic in head injured patients moreover potentially has a deleterious effect in patients at risk of raised intracranial pressure. As such other agents are preferred in patients who have suffered a significant neurological affront. (Shea et al., 2002)


The macrolide antibiotic, erythromycin, when administered in sub-antibiotic doses (70-250 mg), acts as a motilin agonist in addition to stimulates gastric motility. Motilin receptors are found in abundance in the gastric antrum plus proximal duodenum along with induce contractions in the gastrointestinal tract. Intravenous erythromycin augments antral motility as well as accelerates gastric emptying in unselected critically sick patients moreover reduces GRV in critically sick patients by means of feed intolerance. Erythromycin is a further effective pro-kinetic than metoclopramide in this patient group. However, as by means of metoclopramide, its effectiveness reduces over time so that following 7 d of treatment just regarding 45% of patients stay tolerant to nasogastric feeding. The blend of erythromycin in addition to metoclopramide is superior to either drug alone by means of less tachyphylaxis. Using a blend of the two drugs, 70% of patients can be effectively fed by nasogastric tube at 6 d. Enthusiasm for the employ of erythromycin is tempered by fears of cardiac toxicity plus bacterial resistance. Clinicians have to remain vigilant to drug interactions in critically sick patients, as patients might be on multiple drugs that predispose to a prolonged QT interval. It is likely that cardiac toxicity is minimised by using low dose therapy. A recent report by Parrish et al., (2003) demonstrated that 70 mg erythromycin IV to be as effective as 200 mg in improving gastric emptying in the critically sick. Currently intravenous erythromycin is obtainable in 500 mg ampoules along with it might be easier to administer 100 mg rather than 70 mg at the bedside. The optimal timing flanked by doses has not been clarified however is probably flanked by BD in addition to QID. Bacterial resistance remains a concern, regardless of dosing schedule, as well as investigation of motilin agonists devoid of antibiotic effect or other unrelated agents is warranted. (Parrish et al., 2003)

 Opiate receptor antagonists

As opiate administration might be a significant cause of reduced gastrointestinal motility along with unsuccessful feeding in the critically sick, opiate antagonists are logical options for treatment. To avoid antagonism of required analgesic plus sedating properties naloxone has been administered via a nasogastric tube. Eight mg naloxone administered every 6 h, via nasogastric tube, reduced GRV in 84 mechanically ventilated patients who were receiving â…£ fentanyl. The treatment group in addition had a lower incidence of ventilator associated pneumonia (VAP). However, the decreased incidence of VAP in the naloxone group did not lead to a reduction in time to wean as of mechanical ventilation, or time to discharge as of ICU in addition to the efficacy of naloxone requires confirmation. As naloxone is packaged in 400 mg ampoules, a dose of 8 mg involves the inconvenience of opening 20 ampoules 4 times a day. This restricts easy administration moreover augments expense, which might have limited the uptake of this approach. There has in addition been research into other mu receptor blockers, such as Alvimopan, a peripheral mu-opioid receptor antagonist. Significantly, unlike naloxone this agent does not antagonise opioid analgesia. Alvimopan reverses the inhibitory effect of opiate on small bowel motility as measured by scintigraphy moreover has been worn successfully in postoperative patients to shorten both the time to bowel recovery in addition to time to discharge as of hospital. However, it has not been formally assessed in critically sick patients. (Parrish et al., 2003)

 CCK receptor antagonists

Elevated CCK levels inhibit gastric emptying plus motility in health as well as are associated by means of feed intolerance in critically sick patients. CCK1 receptors antagonists have been reported to improve lower oesophageal sphincter function along with accelerate gastric emptying. This class of drug therefore has potential as an effective treatment for deferred gastric emptying in addition to feed intolerance in the critically sick however this has not been examined. (Parrish et al., 2003)

 5-HT4 receptor agonists

Serotonin (5-Hydroxytryptamine), a monoamine neurotransmitter, acts on a variety of receptor types in the gastrointestinal tract by means of the effect of serotonin depending on the receptor type that is expressed. As 5-HT4 stimulates peristalsis there had been interest in the employ of these drugs as pro-kinetic agents, following their successful employ in irritable bowel syndrome. Tegaserod, a serotonin partial agonist, had been reported to augment gastric motility in critically sick patients. However, in March 2007 the FDA requested Tegaserod be reserved due to an augment in cardiovascular side effects. The mechanism of this unclear, however reminds critical care clinicians to remain cautious when prescribing recently introduced drugs for off licence indications. (Parrish et al., 2003)


Ghrelin is a natural ligand for the growth hormone (GH) receptor plus has strong GH releasing activity. A motilin related peptide, ghrelin has a number of other actions including stimulation of appetite (hence the label of the "fattening" peptide, gastro kinetic effects as well as positive inotropic effect on the circulation. The motility effects comprise induction of gastric phase 3 contractions as well as increasing the resting tone of the proximal stomach. Ghrelin has been successfully worn as a pro-kinetic in diabetic gastro-paresis. Treatment by means of an agent that has anabolic effects, improves gastrointestinal motility as well as providing circulatory support has inherent desirable properties. However, there are no data as yet on the employ of ghrelin in the critically sick; moreover enthusiasm for exogenous administration of the peptide is tempered by previous studies where the employ of GH in the critically sick was associated by means of augmented mortality. (Horowitz et al., 1989)


Provision of adequate nutrition in critical sickness is generally accepted as desirable moreover early feeding is considered superior to deferred feeding. The enteral route is preferred as it is cheaper, moreover might be associated by means of less sepsis; however, the high incidence of gastric plus small intestinal dysmotility slows gastric emptying as well as frequently limits nasogastric delivery of nutrients. Even though in widespread employ, gastric residual volumes are an unreliable measure of gastric emptying, might underestimate tolerance to nasogastric feeding moreover do not predict complications such as regurgitation in addition to aspiration? Deferred gastric emptying probably results as of disturbances in the occurrence along with organisation of contractions in both the proximal plus distal stomach. Augmented neuro-hormonal feedback in response to relatively small amounts of nutrient in the small intestine, possibly mediated by CCK might contribute to this motor dysfunction. Awareness of patients at risk for deferred gastric emptying in addition to pre emptive management might decrease the incidence of feed intolerance amongst critically sick patients. The current best treatment of patients who fail nasogastric feeding is pro-kinetic therapy. A blend of erythromycin as well as metoclopramide might reduce the common problem of tachyphylaxis. The dose of erythromycin to promote motility might be smaller than previously appreciated moreover might alleviate a number of concerns relating to adverse side effects. If pro-kinetics fail, delivery of post pyloric nutrition have to be considered. Changes in nutritional management in the future might comprise better means to identify patients at risk of deferred gastric emptying, accepting higher gastric residual volumes, plus the employ of nutrients designed to optimise gastric emptying. Novel agents, including antagonists to CCK or opiates, as well as agonists of ghrelin or motilin, need further investigation. (Parrish et al., 2003)