Gastroparesis De \201 ned as a symptomatic, chronic disorder characterized by delayed gast ric emptying and the absence of mechanical obstruction. Symptoms include early satiety, nau sea, vomit- ing, bloating and upper abdominal discomfort. Gastric food retention can lead t o bezoar formation. May be idiopathic \200 319 CHAPTER 20.1 Vomiting and gastric stasis/gastroparesis 4 Prokinetics: of medication, provided small bowel motility is pre- served. A trial period of NJ feeding i s sensible prior to jejunostomy placement. Gastrostomy tubes can assist in symptom control by allowing venting and draining of the stomach. Again the results of initial nasogastric d ecom- pression can help predict outcome. Metoclopramide: has prokinetic effects on proximal gut via 5-HT4 agonist and weak 5-HT3 ant agonist action. Also central dopamine receptor antagonist, giv- ing antiemetic effect. Loss of effectiveness with time and high incidence of CNS side effects (dystonias, drowsiness, Parkinsonism) limit use to the short term. Domperidone: peripheral D2 receptor antagonist w ith similar prokinetic effects to metoclopramide, but less able to cross blood \200\223brai n barrier, therefore fewer CNS side effects. Improvements in gastric emptying may be transi tory, with continued symptomatic relief being due to additional antiemetic properties. Eryt hromycin: macrolide antibiotic that acts via gas- troduodenal motilin receptors, enhancing antral con- tractility. Most effective when given IV in severe refractory gastroparesis. GI side effects (nausea/vom- iting/abdominal pain) can limit clinical effectiveness. Tegasero d: partial 5-HT4 agonist. Enhances gastric emptying in healthy volunteers, but little evide nce for effectiveness in gastroparesis. Cisapride: 5-HT4 agonist with proven long-term effe c- tiveness in increasing gastric emptying and improving symptoms. Withdrawn from market, h owever, due to action on cardiac potassium channels, leading to case reports of prolonged Q T interval, cardiac arrhythmias and sudden death. Can still be prescribed on a named patien t basis, provided there is no history of conduc- tion defects or concurrent medications kno wn to affect the QT interval. 2 Pyloric botulinum toxin: the increased pyloric tone seen in diabetic gastroparesis can be reduced (for a number of months) by pyloric botulinum toxin injection, but there are few s tudies as yet to support clinical effectiveness. 3 Gastric stimulation: electrodes are attached to the stomach at laparoscopy/laparotomy, an d connected to a subcutaneous electrical stimulator. Gastric pacing uses stimulation at a r ate slightly higher than the intrinsic slow wave frequency ( 3 contractions/min) thus entra in- ing gastric slow waves and accelerating gastric emptying. High frequency stimulation (1 2 contractions/min) has no effect on gastric emptying, but does appear to improve symptoms of nausea and vomiting. Currently the most effective combinations of stimulation parame- te rs remain unde \201 ned. Promising symptomatic improve- ments have been reported, mainly i n diabetic and idiopathic gastroparesis, but more experience is required. Further reading Lin Z, Forster J, Sarosiek I, McCallum RW. Treatment of gastropare- sis with electrical stimulation. Dig Dis Sci 2003; 48: 837 \200\22348. Parkman HP, Hasler WL, Fisher RS; American Gastroenterological Association. American Gastro enterological Association technical review on the diagnosis and treatment of gastroparesis. Gastroenterology 2004; 127: 1592 \200\223622. For those patients with symptoms refractory to dietary manipulation, antiemetics and prokin etics, the following can be considered: 1 Enteral feeds/gastrostomy: placing a jejunostomy can be effective, both for nutrition and for the administration 320 I RECHNER Gastric erosions 2 H+/pepsin/bile seep in and damage intracellular compo- De \201 nition Varies from mild erosions to ulcerations of the gastric mucosa. nents 3 Mucosal necrosis leads to ulcer formation Pepsin is still active unless pH >7 1 pH 5 \200\2237: pepsin still dissolves clot 2 pH <5. 4: pepsin prevents clot formation NB: alkaline gastric contents are not necessary for preve n- tion, and there is no evidence that hypersecretion of pep- sin per se is responsible for erosions Epidemiology Found in patients with a critical illness, which can effect all ages and occur in acute and chronic disease states. Incidence The incidence quoted in the 1980s is below. The true inci- dence now is dif \201 cult to determine, but the perception is that it is very much less than it used to be. 1 E rosions 40 \200\22350% 2 Ulcers 5% 3 Macroscopic/clinically relevant bleeding <2% Intracellular pH is probably more important than intragastric pH Prostaglandins result in 1 Increased blood \202 ow 2 Increased mucus production, and possibly mucus secretion 3 Dec reased ulcer incidence and promotion of healing Risk factors 1 Previous ulcer disease 2 Coagulopathy 3 Mechanical ventilation >48h 4 Previo us factors (now questioned): head injury, multiple trauma, severe burns, sepsis/SIRS, hypot ension, hypovol- aemia, renal failure, hepatic failure Bile salt Causes disruption of the mucosal barrier to occur, and pre- vention of duodenal r e \202 ux is associated with signi \201 cant reduction in gastric ulceration. Prevention Prophylaxis Gastric pH control, cytoprotective drugs, nutrition. Acid/pepsin production reduced by Mucosal resistance increased by Enteral feeds Enteral feeds Reduced incidence is also probably due to: 1 Better ICU management 2 Better oxygen and \202 uid management 3 Early NG feeding 4 Improved analgesia 5 Treatment of coagulopathy Prostaglandins ?Prostaglandins Antacids Sucralfate H2 blockers Pathology The site is usually the fundus and body, rarely in the antrum, duodenum or esopha gus 1 Mucosal ulceration: super \201 cial, eroding through to the muscularis mucosae only, little bleeding and heals rapidly. 2 Acute peptic ulceration: deep, through the muscular l ayer where the larger arteries reside, greater bleeding and slower to heal. Treat stress factors \200 \200 \200 Improve gut oxygen delivery Normovolaemia, adequate oxygenation and ventilation Maximize ca rdiac output and GI pressure Nasogastric feeds as soon as possible Especially high risk groups \200 \200 \200 \200 Head injury, major trauma, burns Prolonged IPPV Renal failure, hepatic failure Sepsis Factors which in \202 uence the risk of hemorrhage 1 Aspirin, NSAIDs, steroids 2 Alcohol 3 Anticoagulants and dextrans 4 Vitamin K de \201 ciency and platelet defects 5 Vasoconstri ctors Sucralfate or H2 blocker where \200 \200 NG aspiration of blood/ \200\230coffee ground \200\231 Previous peptic ulcer disease Omeprazole \200 \200 Local defense mechanisms include 1 The mucus barrier 2 Surfactants AND HCO3 secreted by muc osa 3 H+ reabsorbed by the mucosa is neutralized by blood- Clinical bleed on H2 blockers Endoscopically proven ulceration not healing with H2 blockers derived HCO3 Shock states result in 1 Mucosal ischaemia Treatment: mild bleed Maximize coagulation status/remove precipitants 1 Vitamin K 2 Stop he parin, NSAIDs other anticoagulants 3 Blood transfusion, FFP, platelets or other procoagulan ts TNF causes thrombosis within the gastric mucosal vessels Sympathetic redistribution of bloo d \202 ow away from the splanchnic bed Antacids Get pH >3.5 (ideally >7). 321 CHAPTER 20.2 Gastric erosions because of both a reduction in pneumonia and a possible reduction in mortality. Cook then w ent on in an RCT to compare ranitidine with sucralfate in 1200 critically ill patients. The re was no difference in mortality (23%) or LOS. The ranitidine group had a clinically signi \201 cant lower rate of GI hemorrhage, 1.7% vs 3.8% (P = 0.02). The VAP rates were 19.1% in the ranitidine group vs 16.2% in the sucralfate group (P = 0.19). A further metanalysis (n = 7128) concluded there was strong evidence of a reduction in clinically important GI bl eeds with H2 receptor antago- nists. In addition, it suggested that sucralfate may be as ef fective in reducing bleeding as gastric pH-altering drugs, and is associated with lower rat es of pneumonia and mor- tality. However, the data were insuf \201 cient to determine the net effect of sucralfate compared with no prophylaxis. It may be best summarized that an ob servational study would give us the true incidence of gastric erosions, now that it is decr easing. Based on this, an RCT comparing no prophylaxis with ranitidine or sucralfate may gi ve a de \201 ni- tive answer. Cushing \200\231s ulcers occur in the esophagus, stomach and duo- denum, initially described by Cushing in association with coma of any cause. Now acce pted as acute peptic ulcera- tion in association with severe head injury and raised ICP. Re sults from increased vagally mediated gastric acid secre- tion and responds to H2 blockade. Curling \200\231s ulcer is a circumscribed (<2cm) duodenal ulcer in patients with >35% bur ns. Also results from gastric acid hypersecretion and responds to H2 blockade. Sucralfate H2 blockers 1 Cimetidine, ranitidine and famotidine are competitive antagonists 2 Increase GI Gram-negative colonization and there is an associated increase of nosocomial pneumonia. Omeprazole 1 Absorbed in the small intestine, short plasma half-life but effective for 24h 2 Binds irreversibly to fundic parietal cell H+/K+ ATPase. 20mg gives 65% inhibition at 4 \200\2236h and 25% inhibition at 24h 3 Results in hypergastrinaemia and potential enterochro- ma \201 n hyperplasia Prostaglandins Aminocaproic acid \200 \200 \200 5g stat and 1g/h for 24h IV 20 \200\22330% reduction in rebleeding 40% reduction in morta lity Endoscopy for assessment If major bleeding then proceed with 1 Resuscitation with airway and cardiovascular support. Will mainly require \202 uid resuscitation and reversal of precipitating factors. 2 Octreotide infusion; 100mcg stat, then 50mcg/h equally effective as sclerotherapy. 3 Pitressin infusion has questionable bene \201 ts in stress Summary Stress ulceration in the critically ill is managed by ensuring adequate resuscitati on and early establishment of enteral feeding. If NG feeding is not established after 48h, 50mg IV ranitidine 8 hourly is recommended, but ensure there is increased surveillance for VAP. ulceration. 4 Endoscopic haemostasis: laser coagulation, electrocoag- ulation. 5 Surgery: partial or total gastrectomy in the setting of uncontrolled GI hemorrhage, but m ortality is high in this group. Further reading Cook D, Guyatt G, Marshall J, et al. A comparison of sucralfate and ranitid ine for the prevention of upper gastrointestinal bleeding in patients requiring mechanical ventilation. Canadian Critical Care Trials Group. N Engl J Med 1998; 338: 791 \200\2237. Nosocomial pneumonia One of the potential adverse effects of increasing the gas- tric pH to prevent stress ulceration is that gastric bacterial growth may be encouraged. This has bee n associated with an increased rate of ventilation associated pneumonia. Cook DJ, Reeve BK, Guyatt GH, et al. Stress ulcer prophylaxis in critically ill patients. R esolving discordant meta-analyzes. JAMA 1996; 275: 308 \200\22314. Studies/evidence Cook \200\231s metanalysis in 1994 recommended stress ulcer prophylaxis in critically ill patients who were mechanically ventilated or who had a coagulopathy. The ev idence at the time supported the use of sucralfate over other agents, Cook DJ, Reeve BK, Scholes LC. Histamine-2-receptor antagonists and antacids in the critica lly ill population: stress ulceration ver- sus nosocomial pneumonia. Infect Control Hosp Ep idemiol 1994; 15: 437 \200\22342. 322 P CONAGHAN AND H REECE-SMITH Diarrhea U&E: evidence of renal failure; Na+ and K+ losses from the gut. Mg2+ and Zn2+ are also comm only depleted in prolonged diarrhea. LFTs: may identify a protein-losing enteropathy CRP Bl ood cultures This is the term used to describe an increased stool fre- quency with increased \202 uidi ty. Given that the differential diagnosis of diarrhea is extremely broad, this chapter will concentrate on acute diarrhea in the critical care setting. \200 \200 Pathophysiology The \201 nal cause of diarrhea is imbalanced water/solute transportation across the GI tract. The cause behind this imbal- ance can be divided into 4 pathophysiolog ical mechanisms: \200 Osmotic: failure of the gut to absorb osmotically active solutes re sults in retention of water within the gut lumen. In the critical care setting this may res ult from ingested compounds (e,g, Mg2+-induced diarrhea, cer- tain laxatives), inef \201 c ient gut mucosa (e.g. bacterial over- growth causing bile salt malabsorption) or inadequate gut length (short gut syndrome). It often involves a mod- erate volume of diarrhea (500 \200\2231000ml/day) which improves with starvation. Secretory: increased secretion or reduc ed absorption of salts and water across the GI mucosa, the latter being more common. This c an be caused for example by bac- terial enterotoxins (Vibrio cholerae; enterotoxic Escheric hia coli) and certain laxatives. It often involves a large volume of diarrhea (>1000ml/day) which does not improve with starvation. In \202 ammatory: loss of mucosal integrity leadi ng often to bloody diarrhea if the colorectum is involved. All causes of colitis produce di arrhea predominantly by this method. Dysmotility: impaired gut motility can occasionally ca use diarrhea, usually in the setting of ileus or, more com- monly, the recovery from ileus, when copious retained water and electrolytes within the small bowel over- whelm the absorp tive potential of the colon. Microbiology \200 Stool culture and analysis for C. dif \201 cile toxin (CDT) in patients who have received antibiotics in the preceding few months. CDT remains positive in patients for some weeks ev en after successful treatment, and so assess- ment of recurrent infection is done on clinic al grounds. Rigid sigmoidoscopy to exclude overt colitis, and biopsy to send for histology and culture. Occasionally pseu- domembranes can be seen in C. dif \201 cile infection (pse u- domembranous colitis) Radiology \200 Abdominal X-ray (AXR): anyone with systemic features or abdominal tenderness. Repeat regula rly if any suspicion of toxic megacolon CXR: anyone with localized peritonism Flexible sigm oidoscopy then colonoscopy if diarrhea persists. Flexible sigmoidoscopy must be carried out with caution in anyone with evidence of acute colitis, and colonoscopy is contraindicated in these circumstances. \200 Common causes of diarrhea in the critically ill These can be summarized as infectious and n on-infectious causes. Infectious causes Clostridium dif \201 cile is the most common infective cause in the crit ically ill, often due to antibiotic usage, especially cephalosporins and quinolones. In cri tically ill patients, C. dif \201 cile diarrhea progresses to fulminant infective colitis in 20% of cases. Risk factors include: \200 \200 \200 \200 \200 \200 Clinical approach History Establish onset, duration, frequency, volume and consist- ency of stool. Additional characteristics such as color, bloody, purulent or offensive are helpful . Dietary, drug and travel histories are vital. Past history of GI or immunosup- pressive d isease should be sought. Systemic symptoms such as fever, anorexia and weight loss may also be present Age >60 \200\22365 Previous use of broad-spectrum antibiotics Underlying malignancy Renal o r pulmonary disease Albumin <25mg/ml Previous antisecretory treatment proton pump inhibitor s Mortality is 20% in fulminant pseudomembranous colitis. Other signi \201 cant infection s include \200 \200 \200 Examination Evidence of dehydration, especially tachycardia and hypo- tension. Abdominal te nderness and especially localized peritonism are a concern and should raise suspicion regar ding occult or impending perforation. Abdominal masses (e.g. Crohn \200\231s, intra-abdomin al abscess) can be present. The abdomen may be distended and tympanitic, which is a concern in colitis. Inspection of the mouth and perineum may give clues to the etiology of the dia rrhea (e.g. Crohn \200\231s), and rectal examination ensures the diar- rhoea is not due to overflow from impaction, rectal tumors or pelvic abscesses. Campylobacter spp. Escherichia coli Salmonella enteritidis; Shigella spp. Non-infectious causes Drugs A large number of drugs can cause diarrhea, although antibiotics are the biggest cause in c ritically unwell patients. This is probably due to the reduction in GI bacterial load leadi ng to an increased luminal carbohydrate concentration. Investigations in acute diarrhea Bloods \200 Supplementary feeding-related diarrhea The use of nasogastric/jejunal feeds is a well-recog nized cause of diarrhea. This may be due to high sodium con- tent or concentrated feeds, le ading to high osmolarity. FBC: raised WCC and differential may help to differenti- ate bacterial and viral infections 323 CHAPTER 20.3 Diarrhea to be no difference in rates of diarrhea between gastric and jejunal feeding sites. Enrichi ng enteral feeds with solu- ble \201 bre has also been shown to reduce the incidence and severity of diarrhea in the critically ill. Pseudo-obstruction and fecal impaction can both be treated by limiting opioid drugs as much as possible and by a short course of stimu- la nt oral and rectal laxatives. However, treatment of the underlying cause is essential to pr event recurrence. In intractable cases of pseudo-obstruction, 2mg neostigmine has been used with some success. Once infection and over \202 ow have been excluded, an antimotility ag ent such as loperamide can be used, building up to 16mg daily. However, reducing the osmolarity of the feed seems to have little effect on the diarrhea. A recent meta-analysis suggested enteral nutrition was no more likely to cause diarrhea than parenteral nutrition. Intestinal ischaemia This can occur after particular operations (e.g. abdominal aortic aneu rysm repair), but also as the result of splanchnic hypoperfusion in shocked patients on ino tropes. Over \202 ow diarrhea in pseudo-obstruction or impaction Both fecal impaction and pseudo-o bstruction can occur in critically ill patients. The former is often as a result of heavy o piate use coupled with immobility, and the latter as a result of systemic illness in any in dividual, but especially those immobile and neurologically impaired. This can be diagnosed by a combination of clinical examination which can mimic bowel obstruction and a cavernous rectum on per rectum examination. Copious gas and liquid are often released on per rectum e xamination, and a rigid sigmoidoscopy or con- trast studies can be used to con \201 rm the diagnosis. Further reading Bricker E, Garg R,Nelson R, et al. Antibiotic treatment for Clostridium dif ficile-associated diarrhea in adults. Cochrane Database Syst Rev 2005; (1): CD004610. Gramlich L, Kichian K, Pinilla J, et al. Does enteral nutrition com- pared to parenteral nu trition result in better outcomes in criti- cally ill adult patients? A systematic review o f the literature. Nutrition 2004; 20: 843 \200\2238. Montejo JC, Grau T, Acosta J, et al. Multicenter, prospective, rand- omized, single-blind s tudy comparing the ef \201 cacy and gastrointes- tinal complications of early jejunal feed ing with early gastric feeding in critically ill patients. Crit Care Med 2002; 30: 796 \200 \223800. Ponec RJ, Saunders MD, Kimmey MB. Neostigmine for the treat- ment of acute colonic pseudo-obstruction. N Engl J Med 1999; 341: 137 \200\22341. Management This depends upon the etiology. The \201 rst step is resuscita- tion of a pote ntially dehydrated patient with electrolyte imbalance, especially hypokalaemia. Infectious causes Most GI infections are responsive to cipro \202 oxacin or met- ronidazol e, and these can be used whilst waiting for sensi- tivities if infection is suspected. The treatment of C. dif \201 cile is with IV or oral metronidazole or oral vancomycin. IV vanc omycin is not suitable. More recently oral and IV teicoplanin have been used. Recurrence ra te is 20%, but most will again respond to a 2nd course of antibiotics. Shang E, Geiger N, Sturm JW, et al. Pump-assisted versus gravity- controlled enteral nutrit ion in long-term percutaneous endo- scopic gastrostomy patients: a prospective controlled t rial. JPEN J Parenter Enteral Nutr 2003; 27: 216 \200\2239. Sheth SG, LaMont JT. Gastrointestinal problems in the chronically critically ill patient. Clin Chest Med 2001; 22: 135 \200\22347. Spapen H, Diltoer M, Van Malderen C, et al. Soluble \201 ber reduces the incidence of dia rrhea in septic patients receiving total enteral nutrition: a prospective, double-blind, ra ndomized, and control- led trial. Clin Nutr 2001; 20: 301 \200\2235. Non-infectious causes Cessation of the offending drugs and slowing NG feeds is the treatmen t for diarrhea caused by these agents. Occasionally a change in regimen is all that is requ ired. Continuous pump-driven feeds as opposed to intermittent enteral feeding are bene \201 cial in this respect. There seems Steevens EC, Lipscomb AF, Poole GV, et al. Comparison of continu- ous vs intermittent nasog astric enteral feeding in trauma patients: perceptions and practice. Nutr Clin Pract 2002; 17: 118 \200\22322. 324 M BOOTH Upper gastrointestinal hemorrhage (non-variceal) suite with experienced staff, but severe bleeds in unsta- ble patients require endoscopy in theater with full moni- toring/resuscitation equipment available and anesthetic personnel present to ensure airway protection and pro- vide general anesthesia if required. There sho uld be facilities to proceed directly to surgery if required. In young, \201 t patients w ith minor bleeds, endoscopy can be performed as an out-patient. Angiography/CT angiography \200\224can be helpful if bleeding source not evident at endoscopy. De \201 nition Generally accepted to mean bleeding arising from any- where between the pro ximal esophagus and the ligament of Treitz (duodenojejunal \202 exure). Clinical features Upper GI bleeding typically presents with haematemesis and/or melaena. Fr esh blood can appear unaltered per rectum (haemochezia) although this degree and rapidity o f upper GI bleeding is usually accompanied by obvious haemodynamic compromise. The jet blac k, tarry appear- ance of melaena and its characteristically pungent smell is usually suf \201 cient to distinguish it from the dark, often maroon color and less offensive odor of m ore distal, colonic bleeding. The only sign in the critical care setting may be blood in na sogastric aspirates. Despite advances in endoscopic management, overall mortality remains a t 8 \200\22310%. Immediate control of bleeding: \200 Endoscopic injection with 1:10 000 adrenaline 4 \200\22316ml in quadrants around bleeding p oint. Usually reserved for ulcers with major stigmata of recent hemorrhage (see Table 20.4. 1). Also for vascular lesions, Dieulafoy lesions. Fibrin glue/thrombin also effective but n ot widely availa- ble. Adherent clots should be dislodged by irrigation to allow appropriat e treatment of underlying lesion. Consider repeat endoscopic therapy for rebleeding, or ear ly planned repeat (12 \200\22324h) if suboptimal views/hae- mostatic results from initial p rocedure. Other endo- scopic options include: Heat application \200\224heater probes, multi polar caogulation (BICAP) \200\224as effective as injection therapy, and some evi- dence of additional effectiveness if used in combination with adrenaline injection in active arteri al bleeding. Mechanical clips \200\224effective but need familiarity with use and can be tr icky to deploy accurately, especially in duodenum. Surgery \200\224for uncontrolled bleedin g or significant rebleeds. Control of bleeding by simple under-running of vessel, although ligation of gastroduodenal/right gastro- epiploic arteries may be required to achieve full control of duodenal ulcer bleed. Vagotomy unnecessary with advent of PPIs. Formal gastrecto my/ulcer excision are options for bleeding gastric ulcers, although simple under-running ma y be prudent in an unstable patient. May be required for bleeding gastric carcinoma/stromal tumor. Recurrent bleeding from the duodenal ulcer despite under-running may necessitate an trectomy, ide- ally with duodenal closure excluding the ulcer crater. Angiographic emboliza tion (coils, foam) \200\224generally reserved for complicated anatomy (e.g. post-surgical, pancreatic pseudoaneurysms), high anesthetic risk patients, failed endoscopic/surgical trea tment Causes \200 \200 \200 \200 \200 \200 \200 Peptic ulcer \200\224duodenal or gastric (50 \200\22370%) Mallory Weiss tear Erosive gastri tis/oesophagitis Dieulafoy lesions Stress-related mucosal damage Upper GI malignancy Vascul ar malformations (telangiectasia, gastric antral vas- cular ectasia (GAVE or watermelon sto mach)) Gastrointestinal stromal tumors (GISTs) Risk factors \200 \200 \200 \200 Helicobacter pylori NSAIDs Aspirin Critical care. Initial assessment Severity is related to patient \200\231s age, co-morbidities, haemo- dyn amic status, diagnosis and risk of rebleeding as assessed endoscopically. These can be quan ti \201 ed using the Rockall score (see Table 20.4.1). Early risk strati \201 cation into low and high risk groups is important for proper management, and allows prompt and safe di scharge of patients in low risk groups. Management Management can be considered in a number of stages:- Prevention of re-bleeding/future bleeding Ulcers \200 Resuscitation \200 \200 PPIs \200\224given IV reduce risk of rebleeding and need for surgery, although no evidence for reduction in all-cause mortality. Profound gastric acid suppression (pH >6) best achiev ed with high dose IV PPI (e.g. IV omeprazole 80mg stat followed by 8mg/h infusion for 72h). This pro- duces optimal conditions for clot stabilization, although overall evidence for s uperiority over other dosage regimes, e.g. once-daily IV PPI, is lacking. Helicobacter pylo ri eradication \200\22490% of duodenal ulcers and 70% of gastric ulcers are H. pylori relat ed. Eradication highly effective and further bleeding episodes rare. Discontinue NSAIDs, as pirin. If undesirable to stop NSAIDs, change to least damaging (e.g. ibuprofen) and continu e PPI inde \201 nitely. Large bore IV access, urinary catheter. Bloods: FBC, U&Es (a raised urea:creatinine ratio i ndi- cates breakdown of blood in the GI tract, and hence an upper GI source), LFTs, cross-m atch, prothrombin time IV \202 uids (avoid normal saline if evidence of chronic liver dis ease) \200\224otherwise no clear evidence for crystalloid vs colloid. Blood transfusion \200\224f hemoglobin <10g/dl or signs of signi \201 cant active hemorrhage. Diagnosis \200 Endoscopy \200\224ideally within 24h in a mild/moderate bleed, and as soon as patient adequ ately resuscitated in severe bleeds. Ideally this should be in a fully equipped endoscopy 325 CHAPTER 20.4 Upper gastrointestinal hemorrhage (non-variceal) Table 20.4.1 Severity scoring system for upper GI hemorrhage. Score Variable 0 1 2 3 Age (yrs) <60 60 \200\22379 \211 80 Shock No shock (SBP>100, pulse <100) Tachycardia (systolic BP>100, pulse>100) Hypotension (SBP <100, pulse >100) Renal failure, liver failure, disseminated malignancy Co-morbidity Nil major Cardiac failure, ischaemic heart disease, any major co-morbidity Diagnosis Mallory Weiss tear, no lesion, no SRH All other diagnoses Malignancy of upper GI tract Major SRH None or dark spot Blood in upper GI tract, adherent clot, visible or spurting vessel Each variable is scored. SRH = stigmata of recent hemorrhage. Initial score 0-2 (low risk) 1% mortality, 3 \200\2235 (medium risk) 9% mortality, 6 \200 \2237 (high risk) 17% mortality. Repeat endoscopy \200\224unnecessary for H. pylori-related duodenal ulcers, but recommended for gastric ulcers to ensure healing and exclude malignancy (initially 6/52 post-bleed), and for those continuing on NSAIDs. Preventive measures include early enteral feeding and routine prophylaxis in high risk pati ents (>48h mechani- cal ventilation, coagulopathy, renal failure). H2-receptor antagonists (e.g. ranitidine), sucralfate and PPIs (nasogastric, or more recently V) all effective in r educing clinically signi \201 cant bleeds, with no \201 rm evi- dence showing superiorit y of any one approach. Vascular malformations/Dieulafoy lesions: \200 Usually respond to heater probe or argon plasma coagu- lation. May require multiple treatme nts, especially GAVE if extensive. Further reading Barkun A, Bardou M Marshall JK. Consensus recommendations for managing pati ents with nonvariceal upper gastrointestinal bleed- ing. Ann Intern Med 2003; 139: 843 \200 \22357. Malignancy \200 External beam radiotherapy can be highly effective at controlling bleeding from gastric ade nocarcinoma. Argon plasma coagulation/alcohol injection less effective. GISTs best treated by surgical excision but if metastatic or patient un \201 t consider GLIVEC. 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. Leontiadis GI, Sharma VK, Howden CW. Proton pump inhibitor treatment for acute peptic ulcer bleeding. Cochrane Database Syst Rev 2006; (1): CD002094. Stress-related mucosal damage in critical care patients \200 Stollman N, Metz DC. Pathophysiology and prophylaxis of stress ulcer in intensive care unit patients. J Crit Care 2005; 1: 35 \200\22345. Mucosal ischaemia from splanchnic hypoperfusion exac- erbated by positive pressure ventilat ion. Incidence of clinically signi \201 cant bleeds probably <5%, but signi \201 cantly i ncreased mortality if occurs. 326 M COWAN, S THOMSON, & T RAHMAN Bleeding varices patients with advanced liver disease and variceal bleeding did show reduced rebleeding and mortality. Platelet trans- fusion may be indicated if the platelet count is signi \201 can t reduced. Gastro-oesophageal varices are present in 50% of patients with cirrhosis. The incidence of bleeding from varices is between 5 and 15% per year. Despite advances in medical and endos copic therapy, acute variceal bleeding is a medi- cal emergency that carries an immediate m ortality of 8% and a 20% chance of death after 6 weeks. Rarely, varices may develop seconda ry to portal or splenic vein thrombo- sis. The prognosis of patients with variceal bleeding sec- ondary to non-cirrhotic portal hypertension is better than that of patients with cirr hosis once the acute episode is controlled. International guidelines for the management of patients with variceal bleeding have been published. Antibiotics Bacterial infections may both precipitate and complicate variceal bleeding in p atients with end-stage liver disease. Empiric antibiotic therapy reduces the risk of reblee ding and mortality from acute variceal hemorrhage. Broad- spectrum antibiotics with good Gr am-negative cover such as a quinolone, third-generation cephalosporin or extended spectrum penicillin should be given routinely. The exact agent will depend upon local resistance pat terns. Assessment of the patient with variceal bleeding Varices should be assumed to be the cause of upper GI bleeding in all patients with chronic liver disease until proven otherwise. The initial clinical assessment should focus upon haemodynamic state and resuscitation require - ment. Patients with chronic liver disease have a high base- line cardiac output with redu ced SVR, and are prone to hypotension. Encephalopathy may develop as a conse- quence of the bleed or a consequence of the decompen- sating illness. Blood should be sent for FBC, clot ting, renal and liver func- tion. Cross-matched blood and clotting factors should be readil y available (see below). Once the patient is stabilized, portal vein Doppler ultrasound to establish the direction of \202 ow and to rule out thrombosis may be helpful. Balloon tamponade In cases where endoscopic control of bleeding is not pos- sible or when i t will be some time before endoscopy will be possible, the use of balloon tamponade may be consid- ered. Once passed, the gastric balloon of the Sengstaken \200\223 Blakemore tube sh ould be in \202 ated with water ( soluble contrast medium) and gentle traction applied b y taping the tube to the side of the face. Effective control of bleeding will occur in 80 \200\22390% of cases. The risk of complications including oesophageal necrosis and perforat ion are high; therefore, de \201 nitive therapy must be performed within 24h. There is no evidence that the routine cooling of such tubes prior to use is helpful. Medical reduction of portal pressure Vasopressin is a potent splanchnic and peripheral vaso con- strictor that has been shown to reduce portal pressure. It has a short plasma half-lif e and must be given as a continu- ous infusion. It may be appropriate to give concurrent IV nitrates to ameliorate peripheral vasoconstriction. Terlipressin is a longer acting synthe tic vasopressin ana- logue that can be given as a 4-hourly bolus. It is associated with few er side effects than vasopressin. Somatostatin and analogs such as octreotide may also be g iven to reduce portal pressure in variceal bleeding. Pharmacological therapy to reduce port al pressure is the \201 rst-line treatment in the management of variceal bleeding and sho uld be initiated as soon as the diagnosis is sus- pected. Vasoactive drugs should continue for 2 \200\2235 days to reduce the risk of rebleeding. Although propranolol is proven to re duce the risk of bleeding, -blockade will reduce blood pressure and amel- iorate the comp ensatory tachycardia induced by hypovol- aemia. It is therefore contraindicated in the sett ing of an acute bleed but should be started once the initial episode is resolved. General measures in management of variceal bleeding Adequate IV access, with wide-bore peri pheral cannulae, should be obtained as a priority. Standard practice is to inset two 14G ca nnulae on the antecubital fossae. CVP monitoring may be useful in guiding resuscitation, bu t abso- lute pressures may be falsely elevated in patients with ascites. The response of CV P (or mixed venous saturation) to a \202 uid load remains a useful measure. Encephalopath y is common in cirrhotic patients and may be a consequence of the bleed or associated patho logy. It is standard practice to give regular lactulose to prevent encephalopathy, although this recommendation is not evi- dence based. Endotracheal intubation may be necessary to e nsure airway protection and is strongly recommended if prolonged therapeutic endoscopy or p lacement of a Sengstaken \200\223Blakemore tube is planned. Resuscitation There is experimental evidence that vigorous resuscitation may provoke reblee ding and increase mortality. Published international guidelines therefore promote prompt bu t cautious blood volume resuscitation with the aim of main- taining haemodynamic stability, adequate renal and cere- bral perfusion and a hemoglobin of 8g/dl. Endoscopic therapy Endoscopy is both diagnostic and therapeutic, and should be performed ur gently once the patient has been trans- fused and stabilized. Guidelines recommend endoscop y is performed within 12h of admission to hospital. A meta-analysis of 10 RCTs showed super ior early control of bleeding from oesophageal varices with endoscopic band ligation relati ve to sclerotherapy. Variceal band ligation is the recommended form of endoscopic therapy, but scle- rotherapy should be performed if band ligation is not tech- nically feasible. Correction of coagulopathy Coagulopathy and thrombocytopaenia are common in patients with d ecompensated chronic liver disease. FFP should be infused if the prothrombin time is prolon ged. Cryoprecipitate may be given if there is hypo \201 brinogenaemia. Recombinant activat ed factor VII did not improve outcome relative to standard therapy in a multi-center placeb o-con- trolled trial. A post hoc analysis of a subpopulation of 327 CHAPTER 20.5 Bleeding varices resuscitation and the correction of coagulopathy, empiric antibiotics and pharmacological t herapy to reduce portal pressure should be given. Endoscopic therapy with band ligation or sclerotherapy can be attempted but may lead to recurrent bleeding from iatrogenic ulceratio n. Local tam- ponade with a urinary catheter inserted per rectum is effective but carries a signi \201 cant risk of local necrosis if the balloon is left in \202 ated. TIPS is effe ctive in uncontrollable bleeding. Bleeding from gastric varices is harder to control than bleeding from oesophageal varices. Injection of cyanoacr- ylate tissue glue is effective in achieving haemostasis and prevents rebleeds. Not all endoscopists are experienced in the use of tissue glue, and in this case consideration should be given to temporary balloon tamponade prior to trans- fer or de \201 nitive therapy. Salvage therapy Rebleeding from oesophageal varices, de \201 ned as further haematemesis o r ongoing transfusion requirements >2h after endoscopic therapy, should be managed by repea t therapeutic endoscopy. If this is unsuccessful, consideration should be given to creation of a portal \200\223systemic shunt. This may be performed radiologically (TIPS) or sur- gi cally. The aim is to reduce the portal venous pressure to <12mm Hg. Early TIPS and surgery have been shown to improve survival in high risk patients. The performance of both surgery and TIPS is dependent upon local ex- pertise. All shunt procedures carry a risk of chronic encephalopathy. TIPS is effective in control of gastric variceal bleeding in 90% of cases. The threshold for TIPS should be lower in bleeding from gastric than oesophageal varices. Further reading Bosch J, Thabut D, Bendtsen F, et al. Recombinant factor VIIa for upper gas trointestinal bleeding in patients with cirrhosis: a rand- omized, double-blind trial. Gast roenterology 2004; 127: 1123-30. de Franchis R. Evolving consensus in portal hypertension. Report of the Baveno IV consensus workshop on methodology of diagnosis and therapy in porta l hypertension. J Hepatol 2005; 43: 167 \200\22376. Garcia-Pagan JC, Bosch J. Endoscopic ba nd ligation in the treatment of portal hypertension. Nature Clin Pract 2005; 2: 526 \200\22335. Garcia-Tsao G, Sanyal AJ, Grace ND, et al. Prevention and manage- ment of gastroesophageal varices and variceal hemorrhage in cir- rhosis. Hepatology 2007; 46: 922 \200\22338. Vangeli M, Patch D, Terreni N, et al. Bleeding ectopic varices \200\224 treatment with tran sjugular intrahepatic porto-systemic shunt (TIPS) and embolisation. J Hepatol 2004; 41: 560 \200\2236. Rectal varices Bleeding from rectal varices is uncommon, and the evi- dence base of most tr eatments is limited. In addition to 328 A REECE-SMITH & S MIDDLETON Intestinal perforation Drug history A variety of drugs can lead to perforation. Commonly NSAIDs and steroids cause gastric or duodenal erosions, but this may also occur with other drugs such as meth- otrex ate. Broad-spectrum antibiotics, chemotherapy or immunosuppressive medication can lead to p seudomem- branous colitis which may perforate if megacolon devel- ops.