Author: FA Manian MD, MPH

Should I use aPTT or anti-Xa levels to monitor my patient on IV heparin infusion?

FA Manian MD, MPH, , , , , , , , , , , , Leave a comment

Despite more than half a century of use unfractionated heparin (UFH), the optimal method to monitor its anticoagulation effect remains unclear, with arguments for and against continued use of activated partial thromboplastin time, aPTT) vs switching to antifactor Xa heparin assay (anti-Xa HA). 1-4

The advantage of aPTT include decades of use and familiarity by providers, and its relative accessibility, ease of automation and cost.1 Its disadvantages include variation among the sensitivities of different aPTT reagents as well as susceptibility to factors that do not reflect intrinsic heparin activity (eg, liver dysfunction, hypercoagulable states). 1,2 Thus patients may receive unnecessarily high or low heparin doses because of physiologic and non-physiologic influences on aPTT.

In contrast, since anti-XA HA measures the inhibition of a single enzyme (factor Xa)1, it is a more direct measurement of heparin activity, with less variability and minimal interference by certain biological factors (eg, lupus anticoagulants). Anti-Xa monitoring may also improve the time to therapeutic anticoagulation and lead to fewer dose adjustments compared to aPTT monitoring.2

The disadvantages of anti-Xa HA include inaccuracy in the setting of hypertriglyceridemia (>360 mg/dL), hyperbilirubinemia (total bilirubin >6.6 mg/dL), recent use of low molecular weight heparin, fondaparinux and direct oral factor Xa inhibitors. Its relative expense and generally less laboratory availability among healthcare facilities may also limit its use in monitoring patients on therapeutic UFH. 1-3

Somewhat unsettling is the frequent discordance between aPTT and anti-Xa values having been reported in 46% to 60% of instances that may result in either thromboembolic or bleeding complications. 1,4 One study reported that aPTT may be therapeutic only 35% of the time that anti-Xa is also therapeutic! 2

What’s clearly missing are definitive studies that can shed light on the clinical impact of these intriguing findings on patient outcomes. So stay tuned!

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References

  1. Guervil DJ, Rosenberg AF, Winterstein AG, et al. Activated partial thromboplastin time versus antifactory Xa heparin assay in monitoring unfractionated heparin by continuous intravenous infusion. Ann Pharmacother 2011;45:861-68. https://www.ncbi.nlm.nih.gov/pubmed/21712506
  2. Whitman-Purves E, Coons, JC, Miller T, et al. Performance of Anti-factor Xa versus activated partial thromboplastin time for heparin monitoring using multiple nomograms. Clinical and Applied Thromosis/Hemostasis 2018;24:310-16. https://www.ncbi.nlm.nih.gov/pubmed/29212374
  3. Fruge KS, Lee YR. Comparison of unfractionated heparin protocols using antifactory XA monitoring or activated partial thrombin time monitoring. Am J Health-System Pharmacy. 2015; 72: S90-S97, https://doi.org/10.2146/sp150016
  4. Samuel S, Allison TA, Sharaf S, et al. Antifactor XA levels vs activated partial thromboplastin time for monitoring unfractionated heparin. A pilot study. J Clin Pharm Ther 2016;41:499-502.
  5. doi:10.1111/jcpt.12415. https://www.ncbi.nlm.nih.gov/pubmed/27381025
Should I use aPTT or anti-Xa levels to monitor my patient on IV heparin infusion?

My patient with jaundice complains of abdominal fullness. How useful is the history or physical exam when assessing for ascites?

FA Manian MD, MPH, , , , , , , , , , Leave a comment

Even in the age of ultrasound, history and physical exam can be useful in assessing for ascites.

History is a good place to start. Of all the questions we often ask when we suspect ascites (eg, increasing abdominal girth, weight gain and ankle swelling), lack of report of ankle swelling is probably the most helpful in excluding ascites (negative likelihood ratio [LR-], 0.1 in a study involving men), followed by no increase in abdominal girth (LR-, 0.17). Conversely, patient reported ankle swelling or increasing abdominal girth may be helpful in suspecting ascites (LR+ 4.12 and 2.8, respectively). 1

Of the various physical signs and maneuvers, absence of peripheral edema is highly associated with the lack of ascites, followed by lack of shifting dullness or fluid wave (LR-, 0.2, 0.3, 0.4, respectively). The presence of a fluid wave may be the most helpful in suspecting ascites, followed by peripheral edema, and shifting dullness (LR+ 6.0, 3.8, 2.7, respectively). 1  Relatively high sensitivities have been reported for shifting dullness (83-88%), while relatively high specificities have been reported for the fluid wave test (82-90%).2,3 An elevated INR may also improve the positive predictive value of shifting dullness and fluid waves.4

So if you don’t get a history of ankle edema and find no evidence of peripheral edema or shifting dullness on exam, the likelihood of ascites is pretty low. On the other hand, if you find a positive fluid wave, you can be pretty sure that the patient has ascites.

Of course, the actual likelihood of detecting ascites also depends on several other factors, including your pre-test probability and the volume of the ascites in the abdominal cavity, with at least ~500 ml of ascites necessary before it can be detected on exam (vs ~100 ml for ultrasound). 2,5

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References

  1. Williams JW, Simetl DL. Does this patient have ascites? How to divine fluid in the abdomen. JAMA 1992;267: 2645-48. https://jamanetwork.com/journals/jama/fullarticle/397285
  2. Cattau EL, Benjamin SB, Knuff TE, et al The accuracy of the physical examination in the diagnosis of suspected ascites. JAMA 1982;247:1164-66. https://www.ncbi.nlm.nih.gov/pubmed/7057606
  3. Cummings S, Papadakis M, Melnick J, et al. The predictive value of physical examinations for ascites. West J Med 1985;142:633-36. https://www.ncbi.nlm.nih.gov/pubmed/3892916
  4. Fitzgerald FT. Physical diagnosis versus modern technology. A review. West J Med 1990;152:377-82. https://www.ncbi.nlm.nih.gov/pubmed/2190412
  5. CDC. Assessment for ascites. https://www.cdc.gov/dengue/training/cme/ccm/Assess%20for%20Ascites_F.pdf. Accessed November 13, 2019.
My patient with jaundice complains of abdominal fullness. How useful is the history or physical exam when assessing for ascites?

My patient with peripheral neuropathy was just diagnosed with monoclonal gammopathy of unclear significance (MGUS). Can these two conditions be related?

FA Manian MD, MPH, , , , , , , , , , Leave a comment

The presence of MGUS in patients with peripheral neuropathy (PN) may be either coincidental or causal. Younger age group (<50 y) and the presence of IgM MGUS increase the likelihood of a causal relationship between MGUS and peripheral neuropathy. 1

The likelihood of a causal relationship is higher in the younger age group because of the very low prevalence of M proteins (less than 1.5%) in this population making coincidental presence of MGUS and PN much less likely. In contrast, this relationship may just be coincidental in older patients because of higher baseline prevalence of MGUS (7% in those over 70 y old). 1  

Similarly, a causal relationship between MGUS and PN may be more likely when the M protein is IgM (vs IgG or IgA). In a study of patients with MGUS and peripheral neuropathy,  31% of patients with IgM MGUS had neuropathy vs 14% for IgA and 6% for IgG MGUS. In fact, among patients with PN without an obvious cause, the prevalence of an M protein may be as high as 10%.2  Whether the relationship between non-IgM MGUS and PN is causal remains unclear.3

Although the exact mechanism of MGUS-related PN is not known, pathologic studies in Waldenstrom macroglobulinemia and multiple myeloma have demonstrated demyelination and widened myelin lamellae associated with monoclonal IgM deposits.1

But before you implicate MGUS as the cause of PN, make sure to exclude common causes of PN, such as diabetes mellitus, alcoholism and potential drugs.

 

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References

  1. Chaudhry HM, Mauermann ML, Rajkumar SV. Monoclonal gammopathy—associated peripheral neuropathy: diagnosis and management. Mayo Clin Proc 2017; 92:838-50. https://www.mayoclinicproceedings.org/article/S0025-6196(17)30118-0/pdf
  2. Kelly JJ Jr, Kyle RA, O’Brien PC, et al. Prevalence of monoclonal protein in peripheral neuropathy. Neurology 1981;31:1480-83. https://www.ncbi.nlm.nih.gov/pubmed/6273767
  3. Nobile-Orazio E, Barbien L, Baldini L, et al. Peripheral neuropathy in monoclonal gammopathy of undetermined significance: prevalence and immunopathogenetic studies. Acta neurol Scand 1992;85:383-90. https://onlinelibrary.wiley.com/doi/10.1111/j.1600-0404.1992.tb06033.x
My patient with peripheral neuropathy was just diagnosed with monoclonal gammopathy of unclear significance (MGUS). Can these two conditions be related?

How can I distinguish serotonin syndrome from neuroleptic malignant syndrome in my patient with fever and mental status changes?

FA Manian MD, MPH, , , , , , , , , , , , , , , , , , , , , , , , Leave a comment

Although there is often an overlap between the clinical presentation of serotonin syndrome (SS) and neuromuscular malignant syndrome (NMS), start out with the physical exam. The presence of hyperreflexia, tremors, clonus, hyperactive bowel sounds, and dilated pupils should make you think of SS, whereas hyporeflexia, “lead-pipe” rigidity in all muscle groups, normal pupils, and normal or decreased bowels sounds suggest NMS in the proper context.1-3 The most sensitive and specific sign of SS is clonus.1

Aside from physical exam findings, symptom onset in relation to the implicated drug may also be important. Onset of symptoms within 12-24 h of the initiation or change of an implicated drug suggests SS, whereas a more delayed onset (often 1-3 days) is more supportive of NMS.1-3  SS also tends to resolve within a few days after discontinuation of the offending agent, while NMS usually takes 9-14 days to resolve. 1-3 Although both SS and NMS can be associated with leukocytosis, elevated CK and low serum iron levels are more common in NMS.2

SS is caused by excess serotonin due to a variety of mechanisms—therefore medications— including inhibition of serotonin uptake ( eg, serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, tricyclic antidepressants, metoclopramide, ondansetron), inhibition of serotonin metabolism (seen with monoamine oxidase inhibitors , including linezolid, methylene blue), increased serotonin release (eg stimulants, including amphetamines, cocaine), and activation of serotonin receptors (eg, lithium), among others. 2

As for medications that can cause NMS, look for neuroleptic agents (eg, haloperidol, olanzapine, quetiapine, risperidone), as well as antiemeics, such as metoclopramide and promethazine.2

 

Bonus Pearl: Did you know that several supplements/herbal products have been associated with serotonin syndrome, including L-tryptophan, St. John’s wort and ginseng?1

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References

  1. Bienvenu OJ, Neufeld K, Needham DM. Treatment of four psychiatric emergencies in the intensive care unit. Crit Care Med 2012;40: 2662-70. https://insights.ovid.com/crossref?an=00003246-201209000-00017
  2. Turner AAH, Kim JJ, McCarron RM, et al. Differentiating serotonin syndrome and neuroleptic malignant syndrome. Current Psychiatry 2019;18: 36. https://www.mdedge.com/psychiatry/article/193418/schizophrenia-other-psychotic-disorders/differentiating-serotonin-syndrome
  3. Dosi R, Ambaliya A, Joshi H, et al. Serotonin syndrome versus neuroleptic malignant syndrome: a challenging clinical quandary. BMJ Case Rep 2014. Doi:10.1136/bcr-2014-204154. https://casereports.bmj.com/content/2014/bcr-2014-204154

 

How can I distinguish serotonin syndrome from neuroleptic malignant syndrome in my patient with fever and mental status changes?

Is there any evidence that routinely wearing gowns and gloves upon entry into the rooms of patients on contact precautions for MRSA or VRE really works?

FA Manian MD, MPH, , , , , , , , , , , Leave a comment

Although routine gowning and gloving in the care of hospitalized patients with methicillin-resistant Staphylococcus aureus (MRSA) or vancomycin-resistant Enterococcus (VRE)—also known as contact precautions (CP)— is considered a standard of care (1), the evidence supporting its effectiveness in preventing endemic hospital-associated multidrug-resistant organism (MDROs) infections is not robust and is often conflicting. In fact, this practice is increasingly being questioned (including by some hospital epidemiologists) as means of preventing endemic transmission of MDROs in hospitals (1-7).

Critics often point out that studies supporting the use of CP in MDROs are observational, involving only outbreak situations where they were instituted as part of a bundled approach (eg, improved hand hygiene), making it difficult to determine its relative contribution to infection prevention (2,6).

In fact, recent cluster-randomized trials have largely failed to demonstrate clear benefit of CP over usual care for the prevention of acquiring MRSA or VRE in hospitalized patients (2,4). Furthermore, a meta-analysis of studies in which CP were eliminated failed to find an increase in the subsequent rates of transmission of MRSA, VRE, or other MDROs (2,7).

Based on these and other studies, some have suggested that in the presence of other infection prevention measures (eg, hand hygiene monitoring), CP be implemented only in select circumstances such as open or draining wounds, severe diarrhea or outbreak situations (3).

 

The United States Centers for Disease Control and Prevention (CDC), along with the Infectious Diseases Society of America (IDSA) and the Society of Healthcare Epidemiologists of America (SHEA), however, continue to recommend implementation of CP in the care of patients with MDROs.  

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References

1. Maragakis LL, Jernigan JA. Things we do for good reasons: contact precautions for multidrug-resistant organisms, including MRSA and VRE. J Hosp Med 2019;14:194-6. https://www.ncbi.nlm.nih.gov/pubmed/30811332
2. Young K, Doernberg SB, Snedcor RF, et al. Things we do for no reason:contact precautions for MRSA and VRE. J Hosp Med 2019;14:178-80. https://www.ncbi.nlm.nih.gov/pubmed/30811326
3. Bearman G, Abbas S, Masroor N, et al. Impact of discontinuing contact precautions for methicillin-resistant Staphylococcus aureus and vancomyin-resistant Enerococcus: an interrupted time series analysis. Infect Control Hosp Epidemiol 2018;39: 676-82. https://www.cambridge.org/core/journals/infection-control-and-hospital-epidemiology/article/impact-of-discontinuing-contact-precautions-for-methicillinresistant-staphylococcus-aureus-and-vancomycinresistant-enterococcus-an-interrupted-time-series-analysis/869CD5E44B339770AC771BC06049B98F
4. Harris AD, Pineles L, Belton B, et al. Universal glove and gown use and acquisition of antibiotic-resistant bacteria in the ICU. A randomized trial. JAMA 2013;310:1571-80. https://www.ncbi.nlm.nih.gov/pubmed/24097234
5. Morgan DJ, Murthy R, Munoz-Price LS, et al. Reconsidering contact precautions for endemic methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus. Infect Control Hosp Epidemiol 2015;36:1163-72. https://www.cambridge.org/core/journals/infection-control-and-hospital-epidemiology/article/reconsidering-contact-precautions-for-endemic-methicillinresistant-staphylococcus-aureus-and-vancomycinresistant-enterococcus/CCB41BF48CEC2185CC4D69AF3730584C
6. Morgan DJ, Wenzel RP, Bearman G. Contact precautions for endemic MRSA and VRE. Time to retire legal mandates. JAMA 2017;318:329-30. https://jamanetwork.com/journals/jama/article-abstract/2635333
7. Marra AR, Edmond MB, Schweizer ML, et al. Discontinuing contact precautions for multidrug-resistant organisms: a systematic literature review and meta-analysis. Am J Infect Control 208;46:333-340. https://www.ncbi.nlm.nih.gov/pubmed/29031432

Disclosures: The listed questions and answers are solely the responsibility of the author and do not necessarily represent the official views of Mercy Hospital-St. Louis or its affiliate healthcare centers, Mass General Hospital, Harvard Medical School or its affiliated institutions. Although every effort has been made to provide accurate information, the author is far from being perfect. The reader is urged to verify the content of the material with other sources as deemed appropriate and exercise clinical judgment in the interpretation and application of the information provided herein. No responsibility for an adverse outcome or guarantees for a favorable clinical result is assumed by the author. Thank you!

 

Is there any evidence that routinely wearing gowns and gloves upon entry into the rooms of patients on contact precautions for MRSA or VRE really works?

Does my patient on chronic prednisone need stress doses of corticosteroids perioperatively?

FA Manian MD, MPH, , , , , , , , , , Leave a comment

There are wide-ranging opinions on stress doses of corticosteroids (CS) in patients on chronic prednisone undergoing surgery, largely due to lack of adequately-sized randomized controlled studies.  Most experts seem to agree, however, that the age-old practice of routinely administering very high doses of hydrocortisone (eg, 100 mg IV every 8 hours) with prolonged taper postoperatively is excessive. 1-7

Couple of questions to consider before you decide on stress doses of CS for your patient with CS-induced (not primary) adrenal suppression. First, is your patient likely to have a suppressed adrenal function? And if so, what type of surgery is he or she about to undergo?

As for the first question, keep in mind that exogenous CS suppress the production of corticotropin (ACTH) and can induce adrenal atrophy that may persist for up to 12 months, an effect that’s dependent not only on their dose but also on their duration and may vary greatly from person to person. 2,4

Generally, a daily prednisone dose of 5 mg or less —irrespective of the duration— is considered unlikely to cause adrenal suppression (unless it’s given at bed time) and therefore should not require stress doses of CS.1 Conversely, clinical features of Cushing’s syndrome and prednisone doses of 20 mg or more daily for more than 3 weeks are likely to be associated with hyphothalamic-pituitary-adrenal (HPA) axis suppression.  Due to possible delay in the recovery of the HPA axis after discontinuation of exogenous CS, you should review not only your patient’s current dose and duration of CS but his or her regimen during the previous year. 2

When in doubt, particularly in patients receiving intermediate doses (eg, between 5 to 20 mg of prednisone daily) or duration of CS, testing the HPA axis (eg, by cosyntropin stimulation) has been suggested by some with the caveats that it’s a grade 2C (weak recommendation, low quality evidence) recommendation,7 and the results may not necessarily predict clinical adrenal insufficiency or be available before surgery. 4  

Once you have decided that your patient may be at risk of adrenal insufficiency during the perioperative period, the stress dose and duration of CS will likely depend on the type of surgery: “minor” (eg, inguinal herniorrhaphy); “moderate” (eg, total joint replacement, peripheral vascular surgery) and “major” (eg, pancreatoduodenectomy, cardiac surgery with cardiopulmonary bypass). 

A popular online resource suggests the following:4

  • Minor surgery or local anesthesia: Give only the morning maintenance dose of CS without any stress doses
  • Moderate surgery: Give the usual morning dose plus hydrocortisone IV 50 mg (or equivalent) just before the procedure followed by 25 mg IV every 8 hours for 24 hours, followed by the maintenance regimen
  • Major surgery: Give the usual morning dose plus hydrocortisone 100 mg IV before anesthesia induction, followed by 50 mg IV every 8 hours for 24 hours, tapering the dose by half each day to maintenance.

Alternatively, for minor and moderate procedures, other authors suggest usual daily dose plus hydrocortisone 50 mg IV before incision, followed by hydrocortisone 25 mg IV every 8 h for 24 h, then the usual daily dose.1  Yet others have recommended giving IV hydrocortisone 25 mg/day for 1 day for minor surgeries, 50-75 mg/day x 1-2 days for moderate surgeries, and 100-150 mg/day for 2-3 days for major surgeries.2-4 Whichever regimen you chose, make sure to give the morning maintenance dose.  

Why is less aggressive stress dosing being favored in these patients? Several reasons come to mind, including:

  •  In normal subjects, endogenous cortisol production rarely rises above 150-200 mg /day even in response to major surgery 2-4   
  • High doses of CS, particularly with long taper, may unnecessarily subject patients to adverse effects, such as hyperglycemia and poor wound healing 3,4
  • Published reports of CS-treated patients having complications such as hypotension or even death in the postoperative period have generally only implicated, not proven, adrenal insufficiency as a cause. 1-4

 

Bonus pearl: Did you know that the hypotension of secondary adrenal insufficiency in patients treated with CS is not caused by mineralocorticoid deficiency? Instead, it may in part be related to the action of CS in enhancing vascular responsiveness to vasopressors (eg, catecholamines).2 

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References

  1. Liu MM, Reidy AB, Saatee S, et al. Perioperative steroid management: Approaches based on current evidence. Anesthesiology 2017;127:166-72. https://anesthesiology.pubs.asahq.org/article.aspx?articleid=2626031
  2. Axelrod L. Perioperative management of patients treated with glucocorticoids. Endocrinol Metab Clin N Am 2003;32:367-83. http://pggweb.com/doc/glucocorticoids.pdf
  3. Salem M, Tainsh RE Jr, Bromberg J, et al. Perioperative glucocorticoid coverage. A reassessment 42 years after emergence of a problem. Ann Surg 1997;219:416-25. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1243159/
  4. Shaw M. When is perioperative ‘steroid coverage’ necessary? Clev Clin J Med 2002;69:9-11. https://www.ncbi.nlm.nih.gov/pubmed/11811727
  5. Urmson K. Stress dose steroids: the dogma persists. Can J Anesthe 2019;September 23. https://www.ncbi.nlm.nih.gov/pubmed/31549340
  6. Wax DB. One size fits all for stress-dose steroids. Anesthesiology 208;128:674-87. https://anesthesiology.pubs.asahq.org/article.aspx?articleid=2672525
  7. Hamrahian AH, Roman S, Milan S. The management of the surgical patient taking glucocorticoids. Uptodate 2019, accessed October 21, 2019. https://www.uptodate.com/contents/the-management-of-the-surgical-patient-taking-glucocorticoids
Does my patient on chronic prednisone need stress doses of corticosteroids perioperatively?

I am admitting a patient with diabetes mellitus (DM) due to chronic pancreatitis. Should I manage her diabetes any differently than my other patients with DM?

FA Manian MD, MPH, , , , , , , , Leave a comment

You may have to!  That’s because patients with DM due to pancreatic disease (also known as “pancreatogenic [Type 3C] diabetes”) tend to have more labile blood glucoses with particular predisposition to severe hypoglycemic episodes due to the impairment of glucagon production by pancreatic alpha-cells. 1-3

This observation dates back to a 1977 study where a high rate of hypoglycemic episodes was found among 59 patients with chronic pancreatitis (most with insulin-dependent DM), including 3 deaths and 2 suffering from severe brain damage following hypoglycemic coma. Interestingly, low basal glucagon levels were found in the latter patients, supporting impairment in glucagon synthesis. Of note, while hypoglycemia is a serious problem in these patients, they are not spared from complications of chronic hyperglycemia, including retinopathy and kidney disease.2

As for the blood glucose management in type 3C DM, since the principle endocrine defect is insulin deficiency, insulin therapy is preferred for most patients, particularly those who are acutely ill or are hospitalized. For otherwise more stable patients with mild hyperglycemia, metformin is an ideal agent as it enhances hepatic insulin sensitivity without the risk of hypoglycemia. As a bonus, metformin may also decrease the risk of pancreatic cancer in chronic pancreatitis, based on observational studies. 4

Also, don’t forget that concurrent pancreatic exocrine insufficiency is common in patients with type 3C DM and requires oral pancreatic enzyme requirement with meals.

Fascinating Pearl: Did you know that in patients with type 3C DM, hyperglycemia is mediated not only by decreased production of insulin, but also by decreased synthesis of pancreatic polypeptide, a peptide that mediates hepatic insulin sensitivity and glucose production? 5

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References

  1. Linde, J, Nilsson LH, Barany FR. Diabetes and hypoglycemia in chronic pancreatitis. Scand J Gastroenterol. 2012;12, 369–373. https://www.ncbi.nlm.nih.gov/pubmed/867001
  2. Andersen D. The practical importance of recognizing pancreatogenic or type 3c diabetes. Diabetes Metab Res Rev. 2012;28:326-328. https://onlinelibrary.wiley.com/doi/abs/10.1002/dmrr.2285
  3. Cui YF, Andersen DK. Pancreatogenic diabetes: Special considerations for management. Pancreatology. 2011;11(3):279-294. doi:10.1159/000329188. https://jhu.pure.elsevier.com/en/publications/pancreatogenic-diabetes-special-considerations-for-management-4
  4. Evans J, Donnelly L, Emsley-Smith A. Metformin and reduced risk of cancer in diabetic patients. Br Med J. 2005;330:1304-1305. https://www.researchgate.net/publication/7888859_Metformin_and_reduced_risk_of_cancer_in_diabetic_patients
  5. Rabiee A. Gafiatsatos P, Salas-Carnillo R. Pancreatic polypeptide administration enhances insulin sensitivity and reduces the insulin requirement of patents on insulin pump therapy. J Diabetes Sci Technol 2011;5:1521-28.  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3262724/

Contributed by Hugo Torres, MD, MPH, Hospital Medicine Unit, Mass General Hospital, Boston, Massachusetts

I am admitting a patient with diabetes mellitus (DM) due to chronic pancreatitis. Should I manage her diabetes any differently than my other patients with DM?

When can I resume anticoagulation in my patient with atrial fibrillation and hemorrhagic stroke?

FA Manian MD, MPH, , , , , , Leave a comment

Optimal timing of resumption of therapeutic anticoagulation (AC) in patients with hemorrhagic stroke or intracranial hemorrhage (ICH) is unclear because of lack of randomized controlled trials, but existing evidence suggests that 4-8 weeks may be reasonable in our patient (1). 
The American Heart Association/American Stroke Association 2015 guidelines recommend avoiding AC for at least 4 weeks in patients without mechanical heart valves (class IIB-very weak), while 1 study reported that prediction models of ICH in atrial fibrillation at high risk of thromboembolic event suggest that resumption of AC at 7-8 weeks may be the “sweet spot” when weighing safety against efficacy of AC in this patient population (1-3).
Two meta-analyses (1 involving patients with non-lobar ICH, another ICH in patients with nonvalvular atrial fibrillation) found that resumption of AC ranging from 10 to 44 days following ICH may be associated with decrease rates of thromboembolic events without significant change in the rate of repeat ICH (4,5).
There are many limitations to the published literature including their retrospective nature, unreported location and size of ICH in many studies, and use of warfarin (not DOACs) as an AC agent (1).
Clearly we need randomized controlled trials to answer this important question. In the meantime, a heavy dose of clinical judgement on a case-by-case basis seems appropriate.

Bonus Pearl: Did you know that lobar ICH has high incidence of cerebral amyloid angiopathy and has been associated with higher bleeding rates than has deep ICH (i.e., involving the thalami, basal ganglia, cerebellum, or brainstem) usually due to hypertensive vessel disease (1)? 

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References
1. Gibson D et al. When is it safe to resume anticoagulation in my patient with hemorrhagic stroke. The Hospitalist, February 5, 2019. https://www.the-hospitalist.org/hospitalist/article/193924/neurology/when-it-safe-resume-anticoagulation-my-patient-hemorrhagic/page/0/1
2. Hemphill JC et al. Guidelines for the management of spontaneous intracerebral hemorrhage. Stroke. 2015 Jul;46:2032-60. https://www.ahajournals.org/doi/pdf/10.1161/STR.0000000000000069
3. Pennlert J et al. Optimal timing of anticoagulant treatment after intracerebral hemorrhage in patients with atrial fibrillation. Stroke. 2017 Feb;48:314-20 https://www.ahajournals.org/doi/pdf/10.1161/STROKEAHA.116.014643
4. Murthy SB et al. Restarting anticoagulation therapy after intracranial hemorrhage: A systematic review and meta-analysis. Stroke. 2017 Jun;48:1594-600. https://www.ahajournals.org/doi/full/10.1161/strokeaha.116.016327
5. Biffi A et al. Oral anticoagulation and functional outcome after intracerebral hemorrhage. Ann Neurol. 2017 Nov;82:755-65 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5730065/

When can I resume anticoagulation in my patient with atrial fibrillation and hemorrhagic stroke?

Should I consider acute acalculous cholecystitis in my elderly ambulatory patient admitted with right upper quadrant pain?

FA Manian MD, MPH, , , , , , , , , , , , , , , , , , , , , , , , Leave a comment

Short answer: Yes! Although we usually associate acute acalculous cholecystitis (AAC) with critically ill patients (eg, with sepsis, trauma, shock, major burns) in ICUs, AAC is not as rare as we might think in ambulatory patients. In fact, a 7 year study of AAC involving multiple centers reported that AAC among outpatients was increasing in prevalence and accounted for 77% of all cases (1)!

 
Although the pathophysiology of ACC is not fully understood, bile stasis and ischemia of the gallbladder either due to microvascular or macrovascular pathology have been implicated as potential causes (2). One study found that 72% of outpatients who developed ACC had atherosclerotic disease associated with hypertension, coronary, peripheral or cerebral vascular disease, diabetes or congestive heart failure (1). Interestingly, in contrast to calculous cholecystitis, “multiple arterial occlusions” have been observed on pathological examination of the gallbladder in at least some patients with ACC and accordingly a name change to “acute ischemic cholecystitis” has been proposed (3).

 
AAC can also complicate acute mesenteric ischemia and may herald critical ischemia and mesenteric infarction (3). The fact that cystic artery is a terminal branch artery probably doesn’t help and leaves the gallbladder more vulnerable to ischemia when arterial blood flow is compromised irrespective of the cause (4).

 
Of course, besides vascular ischemia there are numerous other causes of ACC, including infectious (eg, viral hepatitis, cytomegalovirus, Epstein-Barr virus, Salmonella, brucellosis, malaria, Rickettsia and enteroviruses), as well as many non-infectious causes such as vasculitides and, more recently, check-point inhibitor toxicity (1,5-8).

 
Bonus Pearl: Did you know that in contrast to cholecystitis associated with gallstones (where females and 4th and 5th decade age groups predominate), ACC in ambulatory patients is generally more common among males and older age groups (mean age 65 y) (1)?

 

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References
1. Savoca PE, Longo WE, Zucker KA, et al. The increasing prevalence of acalculous cholecystitis in outpatients: Result of a 7-year study. Ann Surg 1990;211: 433-37. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1358029/pdf/annsurg00170-0061.pdf
2. Huffman JL, Schenker S. Acute acalculous cholecystitis: A review. Clin Gastroenterol Hepatol 2010;8:15-22. https://www.cghjournal.org/article/S1542-3565(09)00880-5/pdf
3. Hakala T, Nuutinene PJO, Ruokonen ET, et al. Microangiopathy in acute acalculous cholecystitis Br J Surg 1997;84:1249-52. https://bjssjournals.onlinelibrary.wiley.com/doi/abs/10.1046/j.1365-2168.1997.02775.x?sid=nlm%3Apubmed
4. Melo R, Pedro LM, Silvestre L, et al. Acute acalculous cholecystitis as a rare manifestation of chronic mesenteric ischemia. A case report. Int J Surg Case Rep 2016;25:207-11. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4941110/
5. Aguilera-Alonso D, Median EVL, Del Rosal T, et al. Acalculous cholecystitis in a pediatric patient with Plasmodium falciparum infection: A case report and literature review. Ped Infect Dis J 2018;37: e43-e45. https://journals.lww.com/pidj/pages/articleviewer.aspx?year=2018&issue=02000&article=00020&type=Fulltext  
6. Kaya S, Eskazan AE, Ay N, et al. Acute acalculous cholecystitis due to viral hepatitis A. Case Rep Infect Dis 2013;Article ID 407182. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3784234/pdf/CRIM.ID2013-407182.pdf
7. Simoes AS, Marinhas A, Coelho P, et al. Acalculous acute cholecystitis during the course of an enteroviral infection. BMJ Case Rep 2013;12. https://casereports.bmj.com/content/12/4/e228306
8. Abu-Sbeih H, Tran CN, Ge PS, et al. Case series of cancer patients who developed cholecystitis related to immune checkpoint inhibitor treatment. J ImmunoTherapy of Cancer 2019;7:118. https://jitc.biomedcentral.com/articles/10.1186/s40425-019-0604-2

 

 

Should I consider acute acalculous cholecystitis in my elderly ambulatory patient admitted with right upper quadrant pain?

When should I suspect invasive pulmonary aspergillosis in my patient with COPD exacerbation?

FA Manian MD, MPH, , , , , Leave a comment

Think of invasive pulmonary aspergillosis (IPA) in your patient when she or he has a COPD exacerbation that appears refractory to broad-spectrum antibiotics and high doses of steroids. Heighten your suspicion even more in patients with severe-steroid dependent COPD, presence of a new pulmonary infiltrate or isolation of Aspergillus spp from respiratory cultures. 1

It’s worth remembering that although dyspnea and bronchospasm are found in most COPD patients with IPA, in contrast to haematological patients, fever, chest pain and hemoptysis are usually absent in this patient population.1

Diagnosis of IPA in this patient population is challenging for several reasons including: 1. A definitive or “proven” diagnosis requires histopathologic evidence of Aspergillus invasion of lung tissue which is not possible without subjecting an already fragile patient to invasive procedures (eg, lung aspiration or biopsy); 2. In contrast to IPA in highly susceptible immunocompromised patients with cancer and recipients of hematopoietic stem cell transplants, standardized definition of IPA in patients with COPD is lacking; 1,3 and 3. Frequent colonization of the respiratory tract of COPD patients with Aspergillus spp (16.3 per 1000 COPD admission in 1 study) 4,5, makes it difficult to diagnose IPA based on cultures alone.

Aside from respiratory cultures, another non-invasive test, serum galactomannan (GM, a polysaccharide antigen that exists primarily in the cell walls of Aspergillus spp and released into the blood during its growth phase 6) may have some utility in suggesting IPA in COPD patients, albeit with a mediocre sensitivity (~30-60%) but respectable specificity (>80 %). In contrast, bronchoalveolar lavage fluid GM may have better sensitivity  (~75%-90%) with similar specificity as that of serum GM in the diagnosis of IPA in these patients 7-8

Bonus pearl: Did you know that the incidence of IPA appears to be increasing in COPD patients requiring ICU admission, with reported mortality rates of 67% to 100%? 7

If you liked this post, download P4P app and sign up under MENU to catch future pearls right into your inbox, all for free!

 

References

  1. Bulpa P, Dive A, Sibille Y. Invasive pulmonary aspergillosis in patients with chronic obstructive pulmonary disease. Eur Res J 2007;30:782-800. https://www.ncbi.nlm.nih.gov/pubmed/17906086
  2. Bulpa P, Bihin B, Dimopoulos G, et al. Which algorithm diagnoses invasive pulmonary aspergillosis best in ICU patietns with COPD? Eur Resir J 2017;50:1700532 https://www.ncbi.nlm.nih.gov/pubmed/28954783
  3. Barberan J, Garcia-Perez FJ, Villena V, et al. Development of aspergillosis in a cohort of non-neutropenic, non-transplant patients colonized by Aspergillus spp. BMC Infect Dis 2017;17:34. https://link.springer.com/article/10.1186/s12879-016-2143-5
  4. Guinea J, Torres-Narbona M, Gijon P, et al. Pulmonary aspergillosis in patients with chronic obstructive pulmonary disease: incidence, risk factors, and outcome. Clin Microbiol Infect 2010; 16:870-77. https://www.sciencedirect.com/science/article/pii/S1198743X14617432
  5. Blot Stijn I, Taccone FS, Van den Abeele A-M, et al. A clinical algorithm to diagnose invasive pulmonary aspergillosis in critically ill patients. Am J Respir Crit Care Med 202;186:56-64. https://www.atsjournals.org/doi/full/10.1164/rccm.201111-1978OC
  6. Pfeiffer CD, Fine JP, Safdar N. Diagnosis of invasive aspergillosis using a galactomannan assay: a meta-analysis. Clin Infect Dis 2006;42:1417-27. https://academic.oup.com/cid/article/42/10/1417/278148
  7. He H, Ding L, Sun B, et al. Role of galactomannan determinations in bronchoalveolar lavage fluid samples from critically ill patients with chronic obstructive pulmonary disease for the diagnosis of invasive pulmonary aspergillosis: a prospective study. Critical Care 2012;16:R138. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5066034/
  8. Zhou W, Li H, Zhang Y, et al. Diagnostic value of galactomannan antigen test in serum and bronchoalveolar lavage fluid samples from patients with nonneutropenic invasive pulmonary aspergillosis. J Clin Microbiol 2017;55:2153-61. https://www.ncbi.nlm.nih.gov/pubmed/28446576
When should I suspect invasive pulmonary aspergillosis in my patient with COPD exacerbation?