- Email: [email protected]
STRESS ULCER PROPHYLAXIS IN CRITICALLY ILL PATIENTS
1255
controlled
study of persistent short-term memory impairment in 10 cannabis-dependent, young middle-class, North American adolescents and in 17 controls matched for age and
IQ. These workers found statistically significant impairment in two out of a battery of six tests of auditory and visually cued short-term memory (Benton selective
test and the Wechsler memory scale prose Deficits lessened but were still detectable after a passages). 6-week interval of relentlessly monitored 24-hour a day supervision and biweekly urine tests for drugs of abuse. It now appears that people who frequently smoke high-potency cannabis can be expected to manifest some short-term subtle memory deficits that continue for at least 6 weeks after their last puff. Individuals with learning disabilities and those who have a borderline or low IQ might be even more susceptible to cannabis-induced deficits of short-term (recent) memory.
visual retention
INVASIVE STREPTOCOCCI STREPTOCOCCI cause may different diseases in man and animals. Species and sometimes varieties or serotypes can be related to particular disorders. Such associations are seen withthe human pathogen Streptococcus pyogenes (Lancefield group A)—representatives of certain serotypes are sometimes called skin, nephritogenic, or even rheumatogenic strains. To these can be added invasive strains. Serotyping of S pyogenes is based on the detection of one or both of the T and M protein antigens on the surface of the bacterial cell and is carried out in only a handful of laboratories worldwide. Distribution of serotypes differs in both time and place. Strains of M-type 1 are plentiful now in the UKand Scandinavia. Apart from outbreaks of minor infections such as sore throat, this serotype is associated especially with invasive disease, including erysipelas. In Canada2 a bacteraemic patient with progressing cellulitis caused by an M-type 1 strain died a few hours after admission, and two nurses got cellulitis arising from areas of dermatitis on their hands. The initial infection in these circumstances often begins on the skin and most such infections are community-acquired. The patient is usually an adult who may present with cellulitis or septic shock. The case-fatality rate exceeds 20%.3 Occasionally streptococcal bacteraemia develops in children without an obvious focus of infection. S pyogenes is the cause of only 2% of positive blood cultures in the UK,4 but when streptococcal bacteraemia occurs the severity and rapidity of the underlying infection can be surprising. The M antigen may be a determinant of bacterial virulence in these patients because, at least in vitro, it confers the ability to survive and multiply in fresh normal human blood. The M protein itself is not intrinsically toxic. The group A streptococcus produces many extracellular antigens, some of which are toxic. A family of four scarlet fever toxins (also known as streptococcal pyrogenic exotoxins) produce erythema of the skin, are pyrogenic and
and enhance susceptibility to endotoxic shock.5 Since 1980 in the UK isolates of S pyogenes from patients with scarlet fever have lacked the A toxin. However, the A toxin is produced by some isolates that were deposited with culture collections fifty years ago.6 Now a report7 by Stevens and colleagues in the USA describes scarlet fever toxin A in strains of S pyogenes isolated from a cluster of 20 patients with severe invasive disease. Eight of the strains tested produced this toxin A and the American researchers conclude that more virulent group A streptococci have reappeared. This may be so, but there are difficulties in relating the toxic state specifically to the production of scarlet fever toxin A. Two strains from patients with bacteraemia in the American study7 did not produce the toxin; neither did three British strains isolated from patients with fatal septicaemia examined in another study.6 It seems that in the UK strains isolated from patients with fatal infections do not produce toxin A. However, many strains in both countries produce scarlet fever toxin B. Invasive streptococcal infection can be compared with meningococcal septic shock. In that condition there is overstimulation of the production of cytokines, including
mitogenic,
necrosis factor (TNF).8 Cytokines are responsible for many of the host responses to bacterial sepsis;9 the name TNF derives from the use by William Coley of mixed culture fluids of S pyogenes and Serratia marcescens for the treatment of cancer.10 TNF is produced by macrophages and monocytes after exposure to endotoxin, which is part of the cell wall of gram-negative bacteria. It is not known whether streptococci or their products can induce TNF, but the fact that a staphylococcal toxin associated with the toxic shock syndrome stimulates production of the factor by monocytes suggests that this possibility is worth investigation. 11I If streptococci do induce TNF, administration of anti-cytokine antibodies in the early stages of invasive streptococcal infections might be helpful. Antibiotics alone often give disappointing results.
tumour
STRESS ULCER PROPHYLAXIS IN CRITICALLY ILL PATIENTS STRESS ulceration associated with critical illness and the risk factors for its development are well known, in both surgical and medical patients. Such ulcers may be clinically silent or may result in massive upper gastrointestinal bleeding.1 The frequency of superficial fundal lesions has PM, Johnson LP, Tomai MA, Handley JP. Characterization and genetics streptococcal pyrogenic exotoxins. In: Ferretti JJ, Curtis R, eds. Streptococcal genetics. Washington, DC: American Society for Microbiology,
5. Schlievert
of group A
1987: 136-42. 6. Hallas G. The production of pyrogenic exotoxins
by group A streptococci. Epidemiol Infect 1985; 95: 47-57. 7. Stevens DL, Tanner MH, Winship J, et al. Severe group A streptococcal infections associated with a toxic-shock-like syndrome and scarlet fever toxin A. N Engl J Med 1989; 321: 1-7. 8. Waage A, Brandtzaeg P, Halstensen A, Kierulf P, Espevik T. The complex patterns of cytokines in serum from patients with meningococcal septic shock. Association between interleukin 6, interleukin 1, and fatal outcome. J Exp Med 1989; 169: 333-38. 9. Michie
1 Gaworzewska E, Colman G. Changes in the pattern of infection caused by Streptococcus pyogenes. Epidemiol Infect 1988; 100: 257-69. 2. Lannigan R, Hussain Z, Austin TW. Streptococcalpyogenes as a causeofnosocomial infection in a critical care unit. DiagMicrobiol Infect Dis 1985; 3: 337-41. 3 Francis J, Warren RE. Streptococcus pyogenes bacteraemia in Cambridge—a review of 67 episodes. QJ Med 1988; 68: 603-13. 4. Young SEJ. Bacteraemia 1975-1980: a survey of cases reported to the PHLS Communicable Disease Surveillance Centre.J Infect 1982; 5: 19-26.
HR, Guillou PJ, Wilmore DW. Tumour necrosis factor and bacterial sepsis. Br J Surg 1989; 76: 670-71. 10. Coley WB. The treatment of inoperable sarcoma by bacterial toxins (the mixed toxins of Streptococcus erysipelas and Bacillus prodigiosus). Proc R Soc Med 1909-10; 3: 1-48 11. Parsonnet
J, Gillis ZA. Production of tumor necrosis factor by human monocytes in response to toxic-shock-syndrome toxin-1. J Infect Dis 1988, 158: 1026-33. 1. Lucas CE, Sugawa C, Riddle J, Rector F, Rosenberg B, Walt AJ. Natural history and surgical dilemma of "stress" gastric bleeding. Arch Surg 1971; 102: 266-73.
1256
been
reported to be up to 100%;2,3 these lesions often occur rapidly-eg, within 24 hours of surgery or of admission for major trauma. Hypersecretion of acid was initially thought to be responsible for the conditionalthough there were conflicting opinions.5 Ritchie and Shearbum6 proposed three prerequisites for stress ulceration--decrease in mucosal blood flow; breakdown of the mucosal barrier (eg, secondary to uraemia or reflux of bile salts); and presence of intraluminal acid. Although Lucas et aP mentioned decreased mucosal blood flow as an initiating factor, efforts for the past 20 years have been directed almost exclusively at neutralisation of intraluminal acid or prevention of acid production. The frequency of macroscopic bleeding seems to have decreased, but it has been suggested that this change has been brought about by improved general resuscitation (possibly by reducing mucosal ischaemia) rather than by specific prophylaxis against stress ulceration.’ Antacid therapy titrated to maintain a favourable gastric pH has long been regarded as the gold standard of prophylaxis but may produce diarrhoea, hypermagnesaemia, and/or alkalaemia when used in the large volumes that may be needed.8 It is also expensive in terms of nursing time.9 Histamine H2 receptor blockers were therefore welcomed as the solution to this disorder. However, the usefulness of these compounds is uncertain for several reasons. Their administration does not guarantee pH controPO,l1 (histamine is not the only stimulus to acid secretion) and studies have not shown an improvement in the frequency of bleeding with pH control versus no treatment or placebo.7,9 H2 receptor blockade itself increases the susceptibility of the gastric mucosa to the effects of intraluminal acid. 12 Moreover, stress ulceration is not related to intraluminal pH but to intramural pH," and patients may bleed despite control of intraluminal pH.14 Some patients maintain a high pH without therapy.15 Bacterial overgrowth occurs in the stomach if the intraluminal pH is high and, whilst early reports did not document a clear link between overgrowth and nosocomial
FC, Rapin M, et al. Acute gastroduodenal lesions related to severe sepsis. Surg Gynecol Obstet 1976; 142: 377-80. 3. Bank S, Misra P, Mausner D, Kurtz L, Rehman M, Wise L. The incidence, distribution and evolution of stress ulcers in surgical intensive care patients. Am J 2. Le Gall Jr, Mignon
Gastroenterol 1980; 74: 76. Idjadi F, Stahl WM, Esslet G. Studies of gastnc secretion
4. Robbms R,
in
stressed
patients. Ann Surg 1972; 175: 555-62. 5. Skillman JJ, Gould SA, Chung RSK, Silen W. The gastric mucosal barrier: clinical and experimental studies in critically ill and normal man, and in the rabbit. Ann Surg 1970; 172: 564-82. 6. Ritchie WP, Shearburn EW. Influence of isoproterenol and cholestyramine on acute gastnc mucosal ulcerogenesis. Gastroenterology 1977, 73: 62-65. 7. Tryba M. Risk of acute stress bleeding and nosocomial pneumonia in ventilated intensive care unit patients: sucralfate versus antacids. Am J Med 1987, 83 (suppl 3B): 117-23. 8. Derrida S, Nury B, Slama R, et al. Occult gastrointestinal bleeding in high-risk intensive care unit patients receiving antacid prophylaxis: frequency and significance. Crit Care Med 1989; 17: 122-25. 9. Borrero E, Ciervo J, Chang JB. Antacid vs sucralfate in preventing acute gastrointestinal tract bleeding in abdominal aortic surgery. Arch Surg 1986; 121: 810-13. 10 Poleski MH, Spanier AH. Cimetidine versus antacids in the prevention of stress erosions in critically ill patients. Am J Gastroenterol 1986; 81: 107-11. 11. Noseworthy TW, Schustack A, Johnston RG, Anderson BJ, Konopad E, Grace M. A randomized clinical trial comparing ranitidine and antacids in critically ill patients. Crit Care Med 1987, 15: 817-19. 12. O’Brien P, Silen W. Influence of acid secretory state on the gastric mucosal tolerance to back diffusion of H+. Gastroenterology 1976; 71: 760-65. 13. Fiddian-Green RG, McGough E, Pittenger G, Rothman E. Predictive value of intramural pH and other risk factors for massive bleeding from stress ulceration. Gastroenterology 1983; 85: 613-20. 14. van den Berg B, van Blankenstein M. Prevention of stress-induced upper gastrointestinal bleeding by cimetidine in patients on assisted ventilation. Digestion 1985, 31: 1-8. 15. Stannard VA, Hutchinson A, Moms DL, Byrne A Gastric exocrine "failure" in critically ill patients: incidence and associated features. Br Med J 1988, 296: 155-56.
pneumonia, the possibility was mentioned. More recent work has reported culture of organisms from the stomach preceding the appearance of the same organism in either blood culture or tracheal aspirates,16and use of H2 receptor blockers is associated with a significant increase in the incidence of nosocomial pneumonia. 17 The body of work on selective decontamination of the digestive tract suggests that selective removal of gram-negative aerobic organisms from the gut may significantly decrease the incidence of nosocomial pneumonia and resultant mortality, though possibly only in specific subgroups of patients." Consequently, since it is well known that the low pH of the normal stomach is largely responsible for the sterility of its contents, it seems unwise to administer a drug whose main effect is to increase the pH. Thus, not only are H2 receptor blockers inappropriate agents for increasing intraluminal pH in critically ill patients, but also the rationale for using any agent to accomplish this end is flawed. Sucralfate, a non-absorbable aluminium salt of sucrose octasulphate, is an agent with no effect on gastric acid secretion and little neutralising capacity. It is said to prevent stress ulceration by stimulating mucus, bicarbonate, and prostaglandin release and mucosal cell renewa1.19 It also has therapeutic actions: it forms a protective layer over ulcers, binds pepsin and bile acids, and has a trophic effect on the gastric mucosa as a whole. In addition, it has antibacterial properties. 20 Studies in 165 patients treated with sucralfate intensive care units suggest that it is as effective as H2 receptor blockers in the prevention of stress ulceration7,9,2122 and have recorded no adverse side-effects attributable to its use.23 Since the mechanism of action of sucralfate is not dependent on control of intraluminal pH, there is no need for pH estimations. Sucralfate is also considerably cheaper than existing H2 receptor blockers. H2 receptor blockers have been advocated for clinically significant gastric bleeding, since intraluminal acid may impair haemostatic mechaniSMS.21 (The efficacy of pH control in such cases had been documented previously.2’) However, a preliminary report of the successful use of high-dose sucralfate in established gastric haemorrhage (in patients who were already being treated with high doses of H2 receptor blockers) has already been published.26 Thus in critically ill patients, sucralfate, which is probably the best prophylactic agent for stress ulceration, may become the treatment of choice in established stress ulcer haemorrhage. on
16. 17
18.
Garvey BM, McCambley JA, Tuxen DV Effects of gastric alkalization on bacterial colonization in critically ill patients Crit Care Med 1989, 17: 211-16 Craven DE, Kunches LM, Kilinsky V, Lichtenberg DA, Make BJ, McCabe WR. Risk factors for pneumonia and fatality m patients receiving continuous mechanical ventilation. Am Rev Respir Dis 1986, 133: 792-96 Ledingham IMcA, Alcock SR, Eastaway AT, McDonald JC, McKay IC, Ramsay G Triple regimen of selective decontamination of the digestive tract, systemic cefotaxime, and microbiological surveillance for prevention of acquired infection in
intensive care. Lancet 1988; i: 785-90 19 Tarnawski A, Hollander D, Gergely H The mechanism of protective, therapeutic and prophylactic actions of sucralfate Scand J Gastroenterol 1987; 22 (suppl 140). 7-13 20. Tryba M, Mantey-Stiers F. Antibacterial activity of sucralfate in human gastric juice Am J Med 1987; 83 (suppl 3B). 125-27. 21 Bresalier RS, Grendell JH, Cello JP, Meyer AA Sucralfate suspension versus titrated antacid for the prevention of acute stress-related gastrointestinal hemorrhage in critically ill patients Am J Med 1987, 83 (suppl 3B) 110-16 22 Laggner A, Lenz K, Base W, Druml W, Schneeweiss B, Grimm G. Prevention of upper gastrointestinal bleeding in long-term ventilated patients Am J Med 1989; 86 (suppl 6A): 81-84 23. Tryba M Side effects of stress bleeding prophylaxis Am J Med 1989; 86 (suppl 6A) 85-93. 24. Green FW, Kaplan MM, Curtis LE, Levine PH Effect of acid and pepsin on blood coagulation and platelet aggregation Gastroenterology 1978; 74: 38-43 25. Simonian SJ, Stratoudakis A, Lawrence M, Mungas J, Blackstone MO Nonsurgical control of massive acute gastnc mucosal hemorrhage with antacid neutralization of gastric content Surg Clin North Am 1976, 56: 21-27. 26. Tryba M, May B. Acute treatment of severe haemorrhagic gastritis with high-dose sucralfate. Lancet 1988; ii: 1304
controlled
study of persistent short-term memory impairment in 10 cannabis-dependent, young middle-class, North American adolescents and in 17 controls matched for age and
IQ. These workers found statistically significant impairment in two out of a battery of six tests of auditory and visually cued short-term memory (Benton selective
test and the Wechsler memory scale prose Deficits lessened but were still detectable after a passages). 6-week interval of relentlessly monitored 24-hour a day supervision and biweekly urine tests for drugs of abuse. It now appears that people who frequently smoke high-potency cannabis can be expected to manifest some short-term subtle memory deficits that continue for at least 6 weeks after their last puff. Individuals with learning disabilities and those who have a borderline or low IQ might be even more susceptible to cannabis-induced deficits of short-term (recent) memory.
visual retention
INVASIVE STREPTOCOCCI STREPTOCOCCI cause may different diseases in man and animals. Species and sometimes varieties or serotypes can be related to particular disorders. Such associations are seen withthe human pathogen Streptococcus pyogenes (Lancefield group A)—representatives of certain serotypes are sometimes called skin, nephritogenic, or even rheumatogenic strains. To these can be added invasive strains. Serotyping of S pyogenes is based on the detection of one or both of the T and M protein antigens on the surface of the bacterial cell and is carried out in only a handful of laboratories worldwide. Distribution of serotypes differs in both time and place. Strains of M-type 1 are plentiful now in the UKand Scandinavia. Apart from outbreaks of minor infections such as sore throat, this serotype is associated especially with invasive disease, including erysipelas. In Canada2 a bacteraemic patient with progressing cellulitis caused by an M-type 1 strain died a few hours after admission, and two nurses got cellulitis arising from areas of dermatitis on their hands. The initial infection in these circumstances often begins on the skin and most such infections are community-acquired. The patient is usually an adult who may present with cellulitis or septic shock. The case-fatality rate exceeds 20%.3 Occasionally streptococcal bacteraemia develops in children without an obvious focus of infection. S pyogenes is the cause of only 2% of positive blood cultures in the UK,4 but when streptococcal bacteraemia occurs the severity and rapidity of the underlying infection can be surprising. The M antigen may be a determinant of bacterial virulence in these patients because, at least in vitro, it confers the ability to survive and multiply in fresh normal human blood. The M protein itself is not intrinsically toxic. The group A streptococcus produces many extracellular antigens, some of which are toxic. A family of four scarlet fever toxins (also known as streptococcal pyrogenic exotoxins) produce erythema of the skin, are pyrogenic and
and enhance susceptibility to endotoxic shock.5 Since 1980 in the UK isolates of S pyogenes from patients with scarlet fever have lacked the A toxin. However, the A toxin is produced by some isolates that were deposited with culture collections fifty years ago.6 Now a report7 by Stevens and colleagues in the USA describes scarlet fever toxin A in strains of S pyogenes isolated from a cluster of 20 patients with severe invasive disease. Eight of the strains tested produced this toxin A and the American researchers conclude that more virulent group A streptococci have reappeared. This may be so, but there are difficulties in relating the toxic state specifically to the production of scarlet fever toxin A. Two strains from patients with bacteraemia in the American study7 did not produce the toxin; neither did three British strains isolated from patients with fatal septicaemia examined in another study.6 It seems that in the UK strains isolated from patients with fatal infections do not produce toxin A. However, many strains in both countries produce scarlet fever toxin B. Invasive streptococcal infection can be compared with meningococcal septic shock. In that condition there is overstimulation of the production of cytokines, including
mitogenic,
necrosis factor (TNF).8 Cytokines are responsible for many of the host responses to bacterial sepsis;9 the name TNF derives from the use by William Coley of mixed culture fluids of S pyogenes and Serratia marcescens for the treatment of cancer.10 TNF is produced by macrophages and monocytes after exposure to endotoxin, which is part of the cell wall of gram-negative bacteria. It is not known whether streptococci or their products can induce TNF, but the fact that a staphylococcal toxin associated with the toxic shock syndrome stimulates production of the factor by monocytes suggests that this possibility is worth investigation. 11I If streptococci do induce TNF, administration of anti-cytokine antibodies in the early stages of invasive streptococcal infections might be helpful. Antibiotics alone often give disappointing results.
tumour
STRESS ULCER PROPHYLAXIS IN CRITICALLY ILL PATIENTS STRESS ulceration associated with critical illness and the risk factors for its development are well known, in both surgical and medical patients. Such ulcers may be clinically silent or may result in massive upper gastrointestinal bleeding.1 The frequency of superficial fundal lesions has PM, Johnson LP, Tomai MA, Handley JP. Characterization and genetics streptococcal pyrogenic exotoxins. In: Ferretti JJ, Curtis R, eds. Streptococcal genetics. Washington, DC: American Society for Microbiology,
5. Schlievert
of group A
1987: 136-42. 6. Hallas G. The production of pyrogenic exotoxins
by group A streptococci. Epidemiol Infect 1985; 95: 47-57. 7. Stevens DL, Tanner MH, Winship J, et al. Severe group A streptococcal infections associated with a toxic-shock-like syndrome and scarlet fever toxin A. N Engl J Med 1989; 321: 1-7. 8. Waage A, Brandtzaeg P, Halstensen A, Kierulf P, Espevik T. The complex patterns of cytokines in serum from patients with meningococcal septic shock. Association between interleukin 6, interleukin 1, and fatal outcome. J Exp Med 1989; 169: 333-38. 9. Michie
1 Gaworzewska E, Colman G. Changes in the pattern of infection caused by Streptococcus pyogenes. Epidemiol Infect 1988; 100: 257-69. 2. Lannigan R, Hussain Z, Austin TW. Streptococcalpyogenes as a causeofnosocomial infection in a critical care unit. DiagMicrobiol Infect Dis 1985; 3: 337-41. 3 Francis J, Warren RE. Streptococcus pyogenes bacteraemia in Cambridge—a review of 67 episodes. QJ Med 1988; 68: 603-13. 4. Young SEJ. Bacteraemia 1975-1980: a survey of cases reported to the PHLS Communicable Disease Surveillance Centre.J Infect 1982; 5: 19-26.
HR, Guillou PJ, Wilmore DW. Tumour necrosis factor and bacterial sepsis. Br J Surg 1989; 76: 670-71. 10. Coley WB. The treatment of inoperable sarcoma by bacterial toxins (the mixed toxins of Streptococcus erysipelas and Bacillus prodigiosus). Proc R Soc Med 1909-10; 3: 1-48 11. Parsonnet
J, Gillis ZA. Production of tumor necrosis factor by human monocytes in response to toxic-shock-syndrome toxin-1. J Infect Dis 1988, 158: 1026-33. 1. Lucas CE, Sugawa C, Riddle J, Rector F, Rosenberg B, Walt AJ. Natural history and surgical dilemma of "stress" gastric bleeding. Arch Surg 1971; 102: 266-73.
1256
been
reported to be up to 100%;2,3 these lesions often occur rapidly-eg, within 24 hours of surgery or of admission for major trauma. Hypersecretion of acid was initially thought to be responsible for the conditionalthough there were conflicting opinions.5 Ritchie and Shearbum6 proposed three prerequisites for stress ulceration--decrease in mucosal blood flow; breakdown of the mucosal barrier (eg, secondary to uraemia or reflux of bile salts); and presence of intraluminal acid. Although Lucas et aP mentioned decreased mucosal blood flow as an initiating factor, efforts for the past 20 years have been directed almost exclusively at neutralisation of intraluminal acid or prevention of acid production. The frequency of macroscopic bleeding seems to have decreased, but it has been suggested that this change has been brought about by improved general resuscitation (possibly by reducing mucosal ischaemia) rather than by specific prophylaxis against stress ulceration.’ Antacid therapy titrated to maintain a favourable gastric pH has long been regarded as the gold standard of prophylaxis but may produce diarrhoea, hypermagnesaemia, and/or alkalaemia when used in the large volumes that may be needed.8 It is also expensive in terms of nursing time.9 Histamine H2 receptor blockers were therefore welcomed as the solution to this disorder. However, the usefulness of these compounds is uncertain for several reasons. Their administration does not guarantee pH controPO,l1 (histamine is not the only stimulus to acid secretion) and studies have not shown an improvement in the frequency of bleeding with pH control versus no treatment or placebo.7,9 H2 receptor blockade itself increases the susceptibility of the gastric mucosa to the effects of intraluminal acid. 12 Moreover, stress ulceration is not related to intraluminal pH but to intramural pH," and patients may bleed despite control of intraluminal pH.14 Some patients maintain a high pH without therapy.15 Bacterial overgrowth occurs in the stomach if the intraluminal pH is high and, whilst early reports did not document a clear link between overgrowth and nosocomial
FC, Rapin M, et al. Acute gastroduodenal lesions related to severe sepsis. Surg Gynecol Obstet 1976; 142: 377-80. 3. Bank S, Misra P, Mausner D, Kurtz L, Rehman M, Wise L. The incidence, distribution and evolution of stress ulcers in surgical intensive care patients. Am J 2. Le Gall Jr, Mignon
Gastroenterol 1980; 74: 76. Idjadi F, Stahl WM, Esslet G. Studies of gastnc secretion
4. Robbms R,
in
stressed
patients. Ann Surg 1972; 175: 555-62. 5. Skillman JJ, Gould SA, Chung RSK, Silen W. The gastric mucosal barrier: clinical and experimental studies in critically ill and normal man, and in the rabbit. Ann Surg 1970; 172: 564-82. 6. Ritchie WP, Shearburn EW. Influence of isoproterenol and cholestyramine on acute gastnc mucosal ulcerogenesis. Gastroenterology 1977, 73: 62-65. 7. Tryba M. Risk of acute stress bleeding and nosocomial pneumonia in ventilated intensive care unit patients: sucralfate versus antacids. Am J Med 1987, 83 (suppl 3B): 117-23. 8. Derrida S, Nury B, Slama R, et al. Occult gastrointestinal bleeding in high-risk intensive care unit patients receiving antacid prophylaxis: frequency and significance. Crit Care Med 1989; 17: 122-25. 9. Borrero E, Ciervo J, Chang JB. Antacid vs sucralfate in preventing acute gastrointestinal tract bleeding in abdominal aortic surgery. Arch Surg 1986; 121: 810-13. 10 Poleski MH, Spanier AH. Cimetidine versus antacids in the prevention of stress erosions in critically ill patients. Am J Gastroenterol 1986; 81: 107-11. 11. Noseworthy TW, Schustack A, Johnston RG, Anderson BJ, Konopad E, Grace M. A randomized clinical trial comparing ranitidine and antacids in critically ill patients. Crit Care Med 1987, 15: 817-19. 12. O’Brien P, Silen W. Influence of acid secretory state on the gastric mucosal tolerance to back diffusion of H+. Gastroenterology 1976; 71: 760-65. 13. Fiddian-Green RG, McGough E, Pittenger G, Rothman E. Predictive value of intramural pH and other risk factors for massive bleeding from stress ulceration. Gastroenterology 1983; 85: 613-20. 14. van den Berg B, van Blankenstein M. Prevention of stress-induced upper gastrointestinal bleeding by cimetidine in patients on assisted ventilation. Digestion 1985, 31: 1-8. 15. Stannard VA, Hutchinson A, Moms DL, Byrne A Gastric exocrine "failure" in critically ill patients: incidence and associated features. Br Med J 1988, 296: 155-56.
pneumonia, the possibility was mentioned. More recent work has reported culture of organisms from the stomach preceding the appearance of the same organism in either blood culture or tracheal aspirates,16and use of H2 receptor blockers is associated with a significant increase in the incidence of nosocomial pneumonia. 17 The body of work on selective decontamination of the digestive tract suggests that selective removal of gram-negative aerobic organisms from the gut may significantly decrease the incidence of nosocomial pneumonia and resultant mortality, though possibly only in specific subgroups of patients." Consequently, since it is well known that the low pH of the normal stomach is largely responsible for the sterility of its contents, it seems unwise to administer a drug whose main effect is to increase the pH. Thus, not only are H2 receptor blockers inappropriate agents for increasing intraluminal pH in critically ill patients, but also the rationale for using any agent to accomplish this end is flawed. Sucralfate, a non-absorbable aluminium salt of sucrose octasulphate, is an agent with no effect on gastric acid secretion and little neutralising capacity. It is said to prevent stress ulceration by stimulating mucus, bicarbonate, and prostaglandin release and mucosal cell renewa1.19 It also has therapeutic actions: it forms a protective layer over ulcers, binds pepsin and bile acids, and has a trophic effect on the gastric mucosa as a whole. In addition, it has antibacterial properties. 20 Studies in 165 patients treated with sucralfate intensive care units suggest that it is as effective as H2 receptor blockers in the prevention of stress ulceration7,9,2122 and have recorded no adverse side-effects attributable to its use.23 Since the mechanism of action of sucralfate is not dependent on control of intraluminal pH, there is no need for pH estimations. Sucralfate is also considerably cheaper than existing H2 receptor blockers. H2 receptor blockers have been advocated for clinically significant gastric bleeding, since intraluminal acid may impair haemostatic mechaniSMS.21 (The efficacy of pH control in such cases had been documented previously.2’) However, a preliminary report of the successful use of high-dose sucralfate in established gastric haemorrhage (in patients who were already being treated with high doses of H2 receptor blockers) has already been published.26 Thus in critically ill patients, sucralfate, which is probably the best prophylactic agent for stress ulceration, may become the treatment of choice in established stress ulcer haemorrhage. on
16. 17
18.
Garvey BM, McCambley JA, Tuxen DV Effects of gastric alkalization on bacterial colonization in critically ill patients Crit Care Med 1989, 17: 211-16 Craven DE, Kunches LM, Kilinsky V, Lichtenberg DA, Make BJ, McCabe WR. Risk factors for pneumonia and fatality m patients receiving continuous mechanical ventilation. Am Rev Respir Dis 1986, 133: 792-96 Ledingham IMcA, Alcock SR, Eastaway AT, McDonald JC, McKay IC, Ramsay G Triple regimen of selective decontamination of the digestive tract, systemic cefotaxime, and microbiological surveillance for prevention of acquired infection in
intensive care. Lancet 1988; i: 785-90 19 Tarnawski A, Hollander D, Gergely H The mechanism of protective, therapeutic and prophylactic actions of sucralfate Scand J Gastroenterol 1987; 22 (suppl 140). 7-13 20. Tryba M, Mantey-Stiers F. Antibacterial activity of sucralfate in human gastric juice Am J Med 1987; 83 (suppl 3B). 125-27. 21 Bresalier RS, Grendell JH, Cello JP, Meyer AA Sucralfate suspension versus titrated antacid for the prevention of acute stress-related gastrointestinal hemorrhage in critically ill patients Am J Med 1987, 83 (suppl 3B) 110-16 22 Laggner A, Lenz K, Base W, Druml W, Schneeweiss B, Grimm G. Prevention of upper gastrointestinal bleeding in long-term ventilated patients Am J Med 1989; 86 (suppl 6A): 81-84 23. Tryba M Side effects of stress bleeding prophylaxis Am J Med 1989; 86 (suppl 6A) 85-93. 24. Green FW, Kaplan MM, Curtis LE, Levine PH Effect of acid and pepsin on blood coagulation and platelet aggregation Gastroenterology 1978; 74: 38-43 25. Simonian SJ, Stratoudakis A, Lawrence M, Mungas J, Blackstone MO Nonsurgical control of massive acute gastnc mucosal hemorrhage with antacid neutralization of gastric content Surg Clin North Am 1976, 56: 21-27. 26. Tryba M, May B. Acute treatment of severe haemorrhagic gastritis with high-dose sucralfate. Lancet 1988; ii: 1304