My hospitalized patient has developed acute nausea, vomiting, and diarrhea. Is there an association between proton pump inhibitors and acute gastroenteritis?

 

Proton pump inhibitors (PPIs) have been associated with increased risk of Clostridium difficile infection, as well as acute gastroenteritis (AG) caused by Salmonella, Campylobacter, and most recently, norovirus. 1,2

A recent prospective study1 of over 38,000 patients (mean age ~ 70 y) found a significant association between PPI use and AG leading to hospitalization with a dose-response relationship.  PPI use increased the risk of Salmonella, Campylobacter, and C. difficile infections.  Of note, H2 receptor antagonists were not associated with AG-related hospitalization in this study.

A 2017 retrospective case-control study also showed an association between PPI use and norovirus infection in hospitalized patients (mean age ~80 y in both groups). Most cases occurred during epidemic years with a median hospital stay of 5 days before onset of symptoms. Given the usually short incubation period of norovirus AG (typically 12-48 h), many of these cases likely acquired the infection during their hospital stay.

Besides reducing the acidity of gastric juice, PPIs may increase the risk of AG by causing an overgrowth of bacteria in the GI tract, reduce its motility and adversely affect the immune response, including neutrophil chemotaxis. 3

Does your patient really need a PPI?

 

References

  1. Chen Y, Liu B, Glass K, et al. Use of proton pump inhibitor and the risk of hospitalization for infectious gastroenteritis. PLoS One 2016;11:e0168618. Doi:10.1371/journal.pone. 0168618.   http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0168618    
  2. Prag C, Prag M, Fredlund H. Proton pump inhibitors as a risk factor for norovirus infection. Epidemiol Infect 2017;145:1617-23. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5426289/pdf/S0950268817000528a.pdf
  3. Wandall JH. Effects of omeprazole on neutrophil chemotaxis, super oxide production, degranulation, and translocation of cytochrome b-245. Gut 1992;33:617-21. https://www.ncbi.nlm.nih.gov/pubmed/1319381
My hospitalized patient has developed acute nausea, vomiting, and diarrhea. Is there an association between proton pump inhibitors and acute gastroenteritis?

Should I consider octreotide in my patient with non-variceal upper GI bleed?

Octreotide is routinely used in the treatment of variceal bleeding due to its vasoconstrictive effects on the splanchnic vasculature.1 In non-variceal upper GI bleed (NVUGB), however, the evidence for routine use of octreotide is hard to come by with an international consensus panel recommending its use only on a case-by-case basis in patients with very active bleeding while awaiting endoscopy or surgery.2,3

These recommendations are based on the failure of several randomized controlled trials in demonstrating the superiority of octreotide in NVUGB over placebo, either alone or with ranitidine, except in a small subset of patients with actively oozing ulcers.4-6 Although a meta-analysis has suggested that octreotide may reduce the risk of continued bleeding in NVUGB,7 the validity of some of the included studies has been questioned.8

On the other hand, octreotide decreases gastric mucosal blood flow and inhibits acid and pepsin secretion, which may potentially benefit patients who are actively bleeding.9

Final fun fact: Did you know that octreotide may be effective in the treatment of chylothorax?

 

References

  1. Avgerinos A, Armonis A, Raptis S. Somatostatin and octreotide in the management of acute variceal hemorrhage. Hepatogastroenterology 1995;42:145-50. http://europepmc.org/abstract/med/7672763
  2. Barkun AN, Barrdou M, Kulpers EJ, et al. International concensus recommendations on the management of patients with nonvariceal upper gastrointestinal bleeding. Ann Intern Med 2010;152:101-113. http://annals.org/aim/article/745521/international-consensus-recommendations-management-patients-nonvariceal-upper-gastrointestinal-bleeding
  3. Barkun A, Bardou M, Marshall JK, Nonvariceal Upper GIBCCG Consensus Conference Group. Consensus recommendations for managing patients with nonvariceal upper gastrointestinal bleeding. Ann Intern Med 2003;139:843–857. https://www.ncbi.nlm.nih.gov/pubmed/14623622
  4. Nikolopoulou VN, Thomopoulos KC, Katsakoulis EC, et al. The effect of octreotide as an adjunct treatment in active nonvariceal upper gastrointestinal bleeding. J Clin Gastroenterol 2004;38:243-7. http://journals.lww.com/jcge/Abstract/2004/03000/The_Effect_of_Octreotide_as_an_Adjunct_Treatment.9.aspx
  5. Archimandritis A, Tsirantonaki M, Tryphonos M, et al. Ranitidine versus ranitidine plus octreotide in the treatment of acute non-variceal upper gastrointestinal bleeding: a prospective randomized study. Curr Med Res Opin. 2000;16(3):178-83. http://www.tandfonline.com/doi/abs/10.1185/0300799009117023
  6. Okan A, Simsek I, Akpinar H, et al. Somatostatin and ranitidine in the treatment of non-variceal upper gastrointestinal bleeding: a prospective, randomized, double-blind, controlled study. Hepatogastroenterology 2000;47:1325-7. http://europepmc.org/abstract/med/11100343
  7. Imperiale TF, Birgisson S. Somatostatin or octreotide compared with H2 antagonists and placebo in the management of acute nonvariceal upper gastrointestinal hemorrhage: a meta-analysis. Ann Intern Med 1997;127:1062–1071. http://annals.org/aim/article/711021/somatostatin-octreotide-compared-h-2-antagonists-placebo-management-acute-nonvariceal
  8. Palmer KR. Non-variceal upper gastrointestinal haemorrhage: guidelines. Gut. 2002;51 (Suppl 4): iv1–iv6. http://gut.bmj.com/content/51/suppl_4/iv1.short
  9. Sgouros SN, Bergele C, Viazis N, et al. Somatostatin and its analogues in peptic ulcer bleeding: facts and pathophysiological aspects. Dig Liver Dis. 2006;38:143-8. http://www.sciencedirect.com/science/article/pii/S1590865805002434

 

Contributed byAlice Choi, Medical Student, Harvard Medical School

 

Should I consider octreotide in my patient with non-variceal upper GI bleed?

Is measurement of amylase and lipase useful in patients with renal insufficiency suspected of pancreatitis?

Depends on how high the serum levels are! Although the clearance of both amylase and lipase appears to be impaired in patients with significant renal insufficiency (eg,  creatinine clearance <50ml/min), serum levels greater than 2-4 times the upper limits of normal for these enzymes are still considered suggestive of pancreatitis in these patients1-3.

Interestingly, in hemodialysis patients, elevation of lipase may also be due to the lipolytic effect of heparin during this procedure.  That’s why obtaining serum lipase levels before, not after,  hemodialysis has been recommended4

Also fascinating is that most of the elevation of serum amylase in patients with significant renal insufficiency appears to be related to the elevation of salivary, not pancreatic, isoenzyme of amylase4.

Final fun fact: Did you know that at one time the diagnosis of pancreatitis was based on the activity of serum on starch (for amylase) and olive oil (for lipase)? 5

References

  1. Levitt MD, Rapoport M, Cooperband SR. The renal clearance of amylase in renal insufficiency, acute pancreatitis, and macroamylasemia. Ann Intern Med 1969;71:920-25. http://annals.org/aim/article/683643/renal-clearance-amylase-renal-insufficiency-acute-pancreatitis-macroamylasemia
  2. Collen MJ, Ansher AF, Chapman AB, et al. Serum amylase in patients with renal insufficiency and renal failure. Am J Gastroenterol 1990;85:1377-80. https://www.ncbi.nlm.nih.gov/pubmed/1699413
  3. Royce VL, Jensen DM, Corwin HL. Pancreatic enzymes in chronic renal failure. Arch Intern Med 1987;147:537-39. https://www.ncbi.nlm.nih.gov/pubmed/2435254
  4. Vaziri ND, Change D, Malekpour A, et al. Pancreatic enzymes in patients with end-stage renal disease maintained on hemodialysis. Am J Gastroenterol 1988;83:410-12. https://www.ncbi.nlm.nih.gov/pubmed/2450453
  5. Editorial. Pancreatic enzymes. N Engl J Med 1963;268:901-2. http://www.nejm.org/doi/pdf/10.1056/NEJM196304182681613
Is measurement of amylase and lipase useful in patients with renal insufficiency suspected of pancreatitis?

Does oral iron cause false-positive stool guaiac test?

The general agreement in the literature is that oral iron supplementation does not cause a false-positive guaiac-based fecal occult blood test (GFOBT).

GFOBT is based on rapid oxidization of α-guaiaconic acid to “guaiacum blue”, with hemoglobin serving as a catalyst through a non-enzymatic or “pseudoperoxidase” action. Although in vitro Fe3+ may serve as an oxidizing agent, this reaction is possible only under acidic conditions not found in the stool (pH ≥ 6-7)1.  Also, in the absence of a catalyst, Fe3+ alone would not be expected to cause rapid (within 30 seconds) conversion of α-guaiaconic acid to guaiacum blue1

Although a number of earlier clinical studies reported false-positive GBFOBT because of oral iron supplementation, subsequent investigations have uniformly failed to confirm these findings2. Potential reasons for earlier false-positive GBFOBT results include false interpretation of the color change—eg, green instead of blue— particularly when the discoloration is weakly positive, and non-standardized method of stool collection with the possibility of stool sample contamination by toilet water.

Other fascinating facts: Did you know that guaiac plant extract was used for centuries for treatment of syphilis and that the earliest application of guaiac testing was in forensic medicine in 1800s?

References

  1. McDonnell WM, Ryan JA, Seeger DM, Elta GH. Effect of iron on the guaiac reaction. Gastroenterology. 1989 Jan;96(1):74-8. https://www.ncbi.nlm.nih.gov/pubmed/2909440
  2. Anderson GD, Yellig TR, Krone RE. An investigation into the effects of oral iron supplementation on in vivo hemoccult stool testing. Am J Gastroenterol 1990;85:558-561. https://www.ncbi.nlm.nih.gov/pubmed/218661

Contributed by Brian Li, Medical Student, Harvard Medical School

Does oral iron cause false-positive stool guaiac test?

When evaluating for an esophageal perforation, is a water-soluble contrast agent such as Gastrografin a better and safer alternative to barium swallow study?

Water-soluble contrast agents (WCAs) (eg, meglumine diatrizoate or Gastrografin) are often ordered as the initial radiographic test for evaluation of esophageal perforation or leaks, followed by barium swallow if the test is negative because small leaks are better detected with the more radiopaque barium1.  Such practice, however, is based on extrapolation of data on the deleterious effect of barium when extravasated into the peritoneal cavity, not the mediastinum1.   In fact, clinical evidence linking mediastinitis to extravasated barium is lacking, and even in experimental studies, injection of barium into the mediastinum of cats have failed to cause clinically significant mediastinitis2.

When ordering a contrast swallow study, no medium should be considered totally safe or effective in detecting esophageal perforations or leaks and WCAs are no different. Potential disadvantages of WCAs include: 1. Inferior sensitivity (as low as 50%)—due to decreased radio-opacity—when compared to barium3; 2. Risk of pulmonary edema—occasionally lethal— when aspirated into the lung due to high osmolality (analogous to salt water drowning) and intense inflammatory reaction4,5; 3. Contraindication in the setting of tracheoesophageal fistula,6; 4. Risk of serious allergic reaction due to reabsorption of iodinated compounds1; and 5. Added exposure to radiation and cost of testing when the swallow study is repeated with barium.  For these reasons, the standard practice of an initial WCA followed by a barium swallow`study if the former is negative, has been questioned, with some centers foregoing the WCA study altogether in favor of barium swallow in certain patients 1,6.

In short, when evaluating for esophageal perforation, WCAs should not categorically be considered a “better” or “safer” alternative to barium; in certain situations, barium may be the preferred agent. When in doubt, input from a thoracic surgeon is recommended.  

 

References

  1. Gollub MJ, Bains MS. Barium sulfate: a new (old) contrast agent for diagnosis of postoperative esophageal leaks. Radiology 1997;202:360-62. https://www.ncbi.nlm.nih.gov/pubmed/9015057
  2. James AE, Montali RJ, Chaffee V, et al. Barium or gastrografin: which contrast media for diagnosis of esophageal tears? Gastroenterology 1975;68:1103-1113. https://www.ncbi.nlm.nih.gov/pubmed/1126592
  3. Berry BE, Ochsner JL. Perforation of the esophagus: a 30 year review. J Thorac Cardiovasc Surg 1973;65:1-7. http://www.jpedsurg.org/article/0022-3468(73)90248-0/abstract
  4. Trulzsch DV, PenmetsaA, Karim A, et al. Gastrografin-induced aspiration pneumonia: A lethal complication of computed tomography. South Med J 1992;85:1255-56. https://www.ncbi.nlm.nih.gov/pubmed/1470976
  5. Tuladhar R, Patole S, Whitehall J. Gastrografin aspiration in a neonate with tracheoesophageal fistula. J Paediatr Child Health 2000; 36:94-6. https://www.ncbi.nlm.nih.gov/pubmed/10723703
  6. FDA https://www.drugs.com/pro/gastrografin.html.
  7. Roh S, Iannettoni MD, Keech JC, et al. Role of barium swallow in diagnosing clinically significant anastomotic leak following esophagectomy. Korean J Thorac Cardiovasc Surg 2016;49:99-109. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4825910/pdf/kjtcv-49-099.pdf

 

When evaluating for an esophageal perforation, is a water-soluble contrast agent such as Gastrografin a better and safer alternative to barium swallow study?

My middle age patient complains of night sweats for several months, but she has had no weight loss and does not appear ill. What could I be missing?

Night sweats (NS) is a common patient complaint, affecting about a third of hospitalized patients on medical wards1.  Despite its long list of potential causes, direct relationship between the often- cited conditions and NS is usually unclear2, its cause may remain elusive In about a third to half of cases in the primary care setting, and its prognosis, at least in those >65 y of age, does not appear to be unfavorable 2,3.

Selected commonly and less frequently cited conditions associated with NS are listed (Table)2-9.  Although tuberculosis is one of the first conditions we think of when faced with a patient with NS, it should be emphasized that NS is not common in this disease (unless advanced) and is rare among hospitalized patients as a cause of their NS1,9.

In one of the larger study of adult patients seen in primary care setting, 23% reported pure NS and an additional 18% reported night and day sweats5; the prevalence of NS in both men and women was highest in 41-55 y age group. In multivariate analyses, factors associated with pure NS in women were hot flashes and panic attacks; in men, sleep disorders. 

Table. Selected causes of night sweats

Commonly cited Less frequently cited
Neoplastic/hematologic (eg, lymphoma, leukemia, myelofibrosis)

Infections (eg, HIV, tuberculosis, endocarditis)

Endocrine (eg, ovarian failure, hyperthyroidism, orchiectomy, carcinoid tumor, diabetes mellitus [nocturnal hypoglycemia], pheochromocytoma)

Rheumatologic (eg, giant cell arteritis)

Gastroesophageal reflux disease

B-12 deficiency

Pulmonary embolism

Drugs (eg, anti-depressants, SSRIs, donepezil [Aricept], tacatuzumab)

Sleep disturbances (eg, obstructive sleep apnea)

Panic attacks/anxiety disorder

Obesity

Hemachromatosis

Diabetes insipidus

References

  1. Lea MJ, Aber RC, Descriptive epidemiology of night sweats upon admission to a university hospital. South Med J 1985;78:1065-67.
  2. Mold JW, Holtzclaw BJ, McCarthy L. Night sweats: A systematic review of the literature. J Am Board Fam Med 2012; 25-878-893.
  3. Mold JW, Lawler F. The prognostic implications of night sweats in two cohorts of older patients. J Am Board Fam Med 2010;23:97-103.
  4. Mold JW, Holtzclaw BJ. Selective serotonin reuptake inhibitors and night sweats in a primary care population. Drugs-Real World Outcomes 2015;2:29-33.
  5. Mold JW, Mathew MK, Belgore S, et al. Prevalence of night sweats in primary care patients: An OKPRN and TAFP-Net collaborative study. J Fam Pract 2002; 31:452-56.
  6. Feher A, Muhsin SA, Maw AM. Night sweats as a prominent symptom of a patient presenting with pulmonary embolism. Case reports in Pulmonology 2015. http://dx.doi.org/10.1155/2015/841272
  7. Rehman HU. Vitamin B12 deficiency causing night sweats. Scottish Med J 2014;59:e8-11.
  8. Murday HK, Rusli FD, Blandy C, et al. Night sweats: it may be hemochromatosis. Climacteric 2016;19:406-8.
  9. Fred HL. Night sweats. Hosp Pract 1993 (Aug 15):88.
My middle age patient complains of night sweats for several months, but she has had no weight loss and does not appear ill. What could I be missing?

My patient with spontaneous bacterial peritonitis (SBP) is requiring IV albumin. Does IV albumin do anything other than expand the plasma volume?

Yes! Besides expanding the circulatory plasma volume by raising the oncotic pressure, albumin appears to have a vasoconstricting effects by binding to endotoxins, nitric oxide (NO), bilirubin and fatty acids1,2. Splanchnic vasodilatation, a feature of decompensated cirrhosis (eg ascites, bleeding varices, hepatorenal syndrome, and hepatic encephalopathy), is accentuated by superimposed infections through cytokine-mediated release of endothelial vasodilators3.  By binding to potential vasodilators such as bile acids, endotoxins and NO, albumin may also help restore endothelial function and act as a vasoconstrictor.  

In a cool study involving patients with SBP randomized to either albumin or hydroxyethyl starch (HS, a synthetic volume expander), the albumin (not HS) group had a significant increase in mean arterial pressure, right atrial pressure, pulmonary artery pressure,  systolic volume, left ventricular stroke work, and systemic vascular resistance3.

Albumin may also have an immune-modulating activity in patients with cirrhosis or acute liver decompensation by binding to prostaglandin E-2 (PGE-2), generated as a result of inflammatory reaction in the liver and bacterial translocation4.  PGE-2 is a suppressor of macrophage cytokine secretion and bacterial killing.  By binding to PGE-2, albumin can reverse this immunosuppression by reducing the availability of serum PGE-2.

References

  1. Baraldi O, Valenini C, Donati G, et al. Hepatorenal syndrome: update on diagnosis and treatment 2015;4:511-20.
  2. Angeli P, Volpin R, Piovan D, et al. Acute effects of the oral administration of midodrine, an α-adrenergic agonist, on renal hemodynamics and renal function in cirrhotic patients with ascites. Hepatology 1998;28:937-43.
  3. Fernandez J, Monteagudo J, Bargallo X, et al. A randomized unblended pilot study comparing albumin versus hydroxyethyl starch in spontaneous bacterial peritonitis. Hepatology 2005;42:627-634.
  4. Gleeson, MW, Dickson RC. Albumin gains immune boosting credibility. Clin Transl 2015;6:e86;doi:10.1038/ctg.2015.11.
My patient with spontaneous bacterial peritonitis (SBP) is requiring IV albumin. Does IV albumin do anything other than expand the plasma volume?