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?

In my critically ill patient with infection, is capillary refill time greater than 2 seconds indicative of septic shock?

The data on the performance of capillary refill time (CRT) in adults is quite limited and what’s available does not suggest that the commonly cited 2 seconds cutoff is useful in assessing peripheral perfusion in critically ill adults1,2.

For example, a large study involving 1000 healthy adults reported that 45% of participants had a CRT > 2 seconds3.  Age also affects CRT with its 95 percentile upper limits reaching 4.5 seconds among healthy adults >60 y old3

Among patients with septic shock, a baseline median CRT of 5 seconds has been reported.  Values <5.0 seconds within 6 hours of treatment of septic shock has also been highly associated with successful resuscitation even before normalization of lactate levels4.

For these reasons, if CRT is used as a measure of peripheral perfusion in critically ill adults, a cut off of 5 seconds, not 2 seconds, may be more appropriate. But just like many other diagnostic tests, CRT should never be interpreted in isolation from other clinical parameters. 

References

  1. Lima A, Bakker J. Clinical Assessment of peripheral circulation. Critical Care 2015:21: 226-31. https://www.ncbi.nlm.nih.gov/pubmed/25827585  
  2. Lewin J, Maconochie I. Capillary refill time in adults. Emerg Med J 2008;25:325-6. https://www.ncbi.nlm.nih.gov/pubmed/18499809
  3. Anderson B, Kelly AM, Kerr D, et al. Impact of patient and environmental factors on capillary refill time in adults. Am J Emerg Med 2008;26:62-65. https://www.ncbi.nlm.nih.gov/pubmed/18082783
  4. Hernandez G, Pedreros C, Veas E, et al. Evolution of peripheral vs metabolic perfusion parameters during septic shock resuscitation. A clinical-physiologic study. J Crit Care 2012;27:283-288.  https://www.ncbi.nlm.nih.gov/pubmed/21798706
In my critically ill patient with infection, is capillary refill time greater than 2 seconds indicative of septic shock?

Do most patients with mycotic aneurysms have endocarditis?

No! In fact, the great majority of patients who develop mycotic aneurysm (MAs) in the postantibiotic era have no evidence of endocarditis1-3.

MAs are thought to be related to microbial arteritis due to blood stream infection of any source with implantation of circulating pathogen (usually bacterial) in atherosclerotic, diseased, or traumatized aortic intima. Plus, MAs may develop due to an adjacent infectious process (eg, vertebral osteomyelitis), either through direct extension or via lymphatic vessels, pathogen seeding of vasa vasorum, or infection of a pre-existing aneurysm1,2.  All these factors may occur in the absence of endocarditis.

Many of your patients may be at risk of MA such as those with advanced age or history of diagnostic or therapeutic arterial catheterization, illicit intravascular drug use, hemodialysis and depressed host immunity1-3..  Staphylococcus aureus, Salmonella sp, S. epidermidis and Streptococcus sp are common culprits in descending order1-3.

So think of MA in your patient with recent blood stream infection,  particularly due to S. aureus or Salmonella sp, in the setting of persistent signs of infection  with or without evidence of endocarditis.

Final Fun Fact: Did you know that the term “mycotic aneurysm” is a misnomer, having been first introduced by Sir William Osler to describe aneurysms of the aortic arch in a patient with (you guessed it) bacterial not fungal endocarditis?

References:

  1. Gomes MN, Choyke PL, Wallace RB. Infected aortic aneurysms: A changing entity. Ann Surg 1992;215:435-42. https://www.ncbi.nlm.nih.gov/pubmed/1616380
  2. Muller BT, Wegener OR, Grabitz K, et al. Mycotic aneurysms of the thoracic and abdominal aorta and iliac arteries: Experience with anatomic and extra-anatomic repair in 33 cases. J Vasc Surg 2001;33:106-13. https://www.ncbi.nlm.nih.gov/pubmed/11137930
  3. Mukherjee JT, Nautiyal A, Labib SB. Mycotic aneurysms of the ascending aorta. Tex Heart Inst J 2012;39:692-5. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3461658/
Do most patients with mycotic aneurysms have endocarditis?

Does methotrexate reduce the risk of cardiovascular events in patients with rheumatoid arthritis?

The weight of the evidence suggests that methotrexate reduces the overall risk of cardiovascular events (CVEs)—including myocardial infarction, congestive heart failure, stroke, and or major adverse cardiac events—in RA patients (RR 0.72, 95% CI 0.57-0.91)1.

Aside from its effect on controlling systemic inflammation, methotrexate has also been shown to increase HDL and reduce total cholesterol/HDL ratio in patients with RA compared with treated non-RA controls2. In vitro, methotrexate appears to activate mechanisms involved in reverse transport of cholesterol out of the cell to the circulation for eventual excretion3. Not surprisingly then, methotrexate has also been reported to decrease atherosclerotic plaque burden measured by carotid artery intima-media thickness2.

We tend to think of RA as a disease that primarily causes arthritis but its effects may extend far beyond the joints. Patients with RA have an increased risk of cardiovascular deaths compared to the general population4, likely due to a variety of factors, including accelerated atherosclerosis secondary to chronic inflammation. At baseline, RA patients also have an unfavorable lipid profile with decreased HDL and higher total cholesterol/HDL ratio.

Fun Final Fact: Did you know that methotrexate is on the WHO Model List of Essential Medicines (April 2015) not only as a cancer drug but for treatment of RA as well5?

References:

  1. Roubille C, Richer V, Starnino T, McCourt C, McFarlane A, Fleming P, Siu S, Kraft J, Lynde C, Pope J, Gulliver W, Keeling S, Dutz J, Bessette L, Bissonnette R, Haraoui B. The effects of tumour necrosis factor inhibitors, methotrexate, non-steroidal anti-inflammatory drugs and corticosteroids on cardiovascular events in rheumatoid arthritis, psoriasis and psoriatic arthritis: a systematic review and meta-analysis. Ann Rheum Dis. 2015;74:480-9. https://www.ncbi.nlm.nih.gov/pubmed/25561362
  2. Georgiadis AN, Voulgari PV, Argyropoulou MI, Alamanos Y, Elisaf M, Tselepis AD, Drosos AA. Early treatment reduces the cardiovascular risk factors in newly diagnosed rheumatoid arthritis patients. Semin Arthritis Rheum 2008;38:13-9. https://www.ncbi.nlm.nih.gov/pubmed/18191989
  3. Reiss AB, Carsons SE, Anwar K, Rao S, Edelman SD, Zhang H, Fernandez P, Cronstein BN, Chan ES. Atheroprotective effects of methotrexate on reverse cholesterol transport proteins and foam cell transformation in human THP-1 monocyte/macrophages. Arthritis Rheum 2008;58:3675-83. https://www.ncbi.nlm.nih.gov/pubmed/19035488
  4. Aviña-Zubieta JA, Choi HK, Sadatsafavi M, Etminan M, Esdaile JM, Lacaille D. Risk of cardiovascular mortality in patients with rheumatoid arthritis: a meta-analysis of observational studies. Arthritis Rheum 2008; 59:1690-7. https://www.ncbi.nlm.nih.gov/pubmed/19035419
  5. WHO Model List of Essential Medicines (April 2015). http://www.who.int/medicines/publications/essentialmedicines/en/

 

Contributed by Brian Li, Medical Student, Harvard Medical School

Does methotrexate reduce the risk of cardiovascular events in patients with rheumatoid arthritis?

What could be causing low serum haptoglobin in my patient with no evidence of hemolysis?

 

There are many causes of low serum haptoglobin besides hemolysis, including1-4:

  • Cirrhosis of the liver
  • Disseminated ovarian carcinomatosis
  • Pulmonary sarcoidosis
  • Elevated estrogen states
  • Repetitive physical exercise
  • Hemodilution
  • Blood transfusions
  • Drugs (eg, oral contraceptives, chlorpromazine, indomethacin, isoniazid, nitrofurantoin, quinidine, and streptomycin)
  • Iron deficiency anemia
  • Megaloblastic anemia (by destruction of megaloblastic RBC precursors in the bone marrow)
  • Congenital causes

Less well-known is that congenital haptoglobin deficiency (“anhaptoglobinemia”) may not be so rare in the general population at a prevalence of 1% among whites and 4% among African-Americans (>30% in blacks of West African origin)3. Measurement of serum hemopexin, another plasma protein that binds heme, may help distinguish between this condition and acquired hypohaptoglobinemia— in the absence of hemolysis, hemopexin levels should remain unchanged3,5.

Final Fun Fact: Did you know that serum haptoglobin is often low during the first 6 months of life?

References

  1. Shih AWY, McFarane A, Verhovsek M. Haptoglobin testing in hemolysis: measurement and interpretation. Am J Hematol 2014;89: 443-47. https://www.ncbi.nlm.nih.gov/pubmed/24809098
  2. Sritharan V, Bharadwaj VP, Venkatesan K, et al. Dapsone induced hypohaptoglobinemia in lepromatous leprosy patients. Internat J Leprosy 1981;307-310. https://www.ncbi.nlm.nih.gov/pubmed/7198620
  3. Delanghe J, Langlois M, De Buyzere M, et al. Congenital anhaptoglobinemia versus acquired hypohaptoglobinemia. Blood 1998;9: 3524. http://www.bloodjournal.org/content/bloodjournal/91/9/3524.full.pdf
  4. Haptoglobin blood test. https://medlineplus.gov/ency/article/003634.htm. Accessed August 6, 2017.
  5. Smith A, McCulloh RJ. Hemopexin and haptoglobin: allies against heme toxicity from hemoglobin not contenders. Front. Physiol 2015;6:187. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4485156/pdf/fphys-06-00187.pdf

 

In collaboration with Kris Olson, MD, MPH, Mass General Hospital, Boston, MA

What could be causing low serum haptoglobin in my patient with no evidence of hemolysis?

How strong is the evidence for IV contrast-induced nephropathy (CIN) following CT scans?

Not as strong as one might expect with an increasing number of investigators questioning the causative role of IV contrast in precipitating CIN.

A 2013 meta-analysis involving observational—mostly retrospective— studies concluded that the risks of AKI, death, and dialysis were similar between IV contrast and non-contrast patients, including those with diabetes or underlying renal insufficiency1.

Two retrospective studies2,3 designed to control for a variety of factors that may affect the risk of AKI by propensity matching found divergent results with the larger and better designed study finding no significant difference in AKI between the 2 groups3. A 2017 retrospective cohort analysis of emergency department patients utilizing a similar propensity-score analysis also failed to find a difference in post-CT AKI between those receiving and not receiving IV contrast4.

Further shedding doubt on the role of IV contrast in causing AKI, a study involving patients with chronic kidney disease found no difference in the rates of excretion of 2 biomarkers of AKI (neutrophil gelatinase-associated lipocalin-NGAL, and kidney injury molecule-1-KIM-1) between patients with and without presumed CIN5. Some have even criticized experimental animal studies supporting the existence of CIN due to their poor applicability to human renal disease1.

This is not to say that IV CIN does not exist. Rather, we should keep an open mind about the pathophysiology and epidemiology of CIN. Stay tuned!

Fun pearl: Did you know that the first case of CIN was described in a patient with multiple myeloma undergoing IV pyelography (before the CT era)?

References

  1. McDonald JS, McDonald RJ, Comin J, et al. Frequency of acute kidney injury following intravenous contrast medium administration: a systematic review and meta-analysis. Radiology. 2013;267(1):119-128. https://www.ncbi.nlm.nih.gov/pubmed/23319662
  2. Davenport MS, Khalatbari S, Dillman JR, et al. Contrast material-induced nephrotoxicity and intravenous low-osmolality iodinated contrast material. Radiology. 2013;267(1):94-105. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3606541/pdf/121394.pdf
  3. McDonald RJ, McDonald JS, Bida JP, et al. Intravenous contrast material-induced nephropathy: causal or coincident phenomenon? Radiology 2013;267:106-18. https://www.ncbi.nlm.nih.gov/pubmed/23360742
  4. Hinson JS, Ehmann MR, Fine DM, et al. Risk of acute kidney injury after intravenous contrast media administration. Ann Emerg Med 2017; 69:577-586. https://www.ncbi.nlm.nih.gov/pubmed/28131489
  5. Kooiman J, van de Peppel WR, Sijpkens YWJ, et al. No increase in kidney injury molecule-1 and neutrophil gelatinase-associated lipocalin excretion following intravenous contrast enhanced-CT. Eur Radio 2015;25:1926-34. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4457910/pdf/330_2015_Article_3624.pdf

Contributed by Ginger Jiang, Medical Student, Harvard Medical School

How strong is the evidence for IV contrast-induced nephropathy (CIN) following CT scans?