How should I manage hypertension in my patient with neurogenic orthostatic hypotension?

The frequent concurrence of supine hypertension (SH) and neurogenic orthostatic hypotension (nOH)1 makes treatment of SH in these patients particularly challenging.

To begin with, your threshold for treatment of SH in patients with neurogenic orthostatic hypotension (nOH) may need to be higher than that commonly recommended by national guidelines for treatment of essential hypertension to avoid exacerbation of nOH.  Although SH in nOH patients is often arbitrarily defined as a systolic BP ≥150 mmHg or diastolic BP≥90 mmHg, a supine systolic BP of up to 160 mmHg may not warrant treatment, particularly if the symptoms of nOH have improved.2

A 2017 consensus panel recommends treatment of SH in the setting of nOH if systolic BP exceeds the range of 160-180 mmHg or diastolic BP exceeds 90-100 mmHg.  “Permissive” approach to SH in this setting may be reasonable, particularly in those with the largest drops in BP upon standing ( >80 mmHg drop). 2

Regardless, all patients with nOH and SH should be advised to avoid supine posture during the day and elevate the head of the bed as tolerated during the night.

If necessary, significant SH may be treated with short acting agents, including2:

  • Captopril 25 mg qhs
  • Clonidine 0.2 mg with evening meal
  • Hydralazine 10-25 mg qhs
  • Losartan 50 mg qhs
  • Nitroglyerine patch 0.1 mg/h patch qhs (remove patch in am)

Long acting antihypertensive agents and diuretics should be avoided given their inherent risk of significant exacerbation of nOH.

 

References

  1. Goldstein DS, Pechnick S, Holmes C, et al. Association between supine hypertension and orthostatic hypotension in autonomic failure. Hypertension 2003; 42:136-142. https://www.ncbi.nlm.nih.gov/pubmed/12835329
  2. Gibbons CH, Schmidt P, Biaggioni I, et al. The recommendations of a concensus panel for the screening, diagnosis, and treatment of neurogenic orthostatic hypotension and associated supine hypertension. J Neurol 2017;264:1567-82. https://www.ncbi.nlm.nih.gov/pubmed/28050656
How should I manage hypertension in my patient with neurogenic orthostatic hypotension?

My patient with low back pain was just diagnosed with a lumbar spinal epidural abscess. Should I order an MRI of the rest of the spine?

First, look closely for any signs or symptoms which may suggest cord involvement due to spinal epidural abscess (SEA) at other levels of the spine (in this case cervical or thoracic) which would necessitate an urgent MRI. Be particularly on the lookout for new pain (particularly radicular) or paresthesias involving the abdomen, chest or upper extremities (with or without weakness)1.

Otherwise, whether an MRI of the entire spine should be routinely obtained after a diagnosis of SEA in the absence of any suggestive signs or symptoms is less clear, in part related to lack of properly designed studies.1-4

Nevertheless, a retrospective study involving 233 patients with SEA may shed some light on the subject. Based on 22 cases of noncontiguous SEA (9.4% of total), the following independent risk factors were identified3:

  • Delay in presentation (≥1 week of symptoms)
  • Concomitant area of infection outside the spine and paraspinal region
  • ESR > 95 mm/h at presentation

Probability of non-contiguous SEA based on the number of risk factors was as follows:

  • 3 risk factors: 73%
  • 2 risk factors: 13%
  • 1 risk factor: 2%
  • Zero risk factor: 0%

Despite several shortcomings and the need to confirm its findings2,3, this study helps raise awareness of the potential for concurrent but asymptomatic SEA elsewhere in the spine whenever SEA is diagnosed.

 

References

  1. Bond A, Manian FA. Spinal epidural abscess: a review with special emphasis on earlier diagnosis. BioMed Res International 2016;Volume 2016, Article ID 1614328. https://www.hindawi.com/journals/bmri/2016/1614328/
  2. Schoenfeld AJ, Hayward RA. Predicting modeling for epidural abscess: what we can, can’t, and should do about it. Spine J 2015;15:102-104. http://www.sciencedirect.com/science/article/pii/S152994301401554X
  3. Ju KL, Kim SD, Melikian R, et al. Predicting patients with concurrent noncontiguous spinal epidural abscess lesions. Spine J 2015;15:95-101. https://www.ncbi.nlm.nih.gov/pubmed/24953159
  4. Pfister HW, vonRosen F, Yousry T. MRI detection of epidural spinal abscesses at noncontiguous sites. J Neurol 1996;243:315-7. https://www.ncbi.nlm.nih.gov/pubmed/8965103
My patient with low back pain was just diagnosed with a lumbar spinal epidural abscess. Should I order an MRI of the rest of the spine?

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?

In my patient on oral anticoagulation about to undergo coronary stenting, will triple therapy (an oral anticoagulant plus two antiplatelet agents) be necessary or can I get away with double therapy (an oral anticoagulant plus a single antiplatelet agent)?

 

Patients with atrial fibrillation (AF) who need percutaneous coronary intervention (PCI) after acute coronary syndrome or for stable angina pose a treatment challenge as oral anticoagulants (OACs) and dual antiplatelet therapy (DAPT) are often used concurrently to decrease the risk of systemic thromboembolism and stent thrombosis. However, “triple therapy”, including aspirin, a P2Y12 inhibitor, and an OAC (eg, warfarin or a direct oral anticoagulant-DOAC), also increases the risk of bleeding, necessitating several recent landmark trials to better address the subject.

Two modest-sized RCTs (WOEST and ISAR-TRIPLE) reported that when compared to triple therapy (DAPT plus warfarin), double therapy (single antiplatelet agent plus INR-targeted warfarin) is associated with reduced risk of bleeding complications without an increased risk of thrombotic events. 1,2

Two larger RCTs, PIONEER AF-PCI and RE-DUAL PCI, studied rivaroxaban and dabigatran, respectively, in patients with non-valvular AF undergoing PCI and found a reduction in bleeding events in patients receiving double therapy (single antiplatelet agent plus DOAC) compared to triple therapy (DAPT plus warfarin), without an increased risk of thrombotic complications. 3,4

Collectively, these studies suggest that it may be safe to treat patients with increased risk of bleeding with double therapy (even immediately following PCI) without an increase in thrombotic events. If triple therapy is elected, duration should be minimized, clopidogrel should be preferred over more potent P2Y12 inhibitors, and a PPI should be considered.

 

References:

  1. Dewilde WJ, Oirbans T, Verheugt FW, et al. Use of clopidogrel with or without aspirin in patients taking oral anticoagulant therapy and undergoing percutaneous coronary intervention: an open-label, randomised, controlled trial. Lancet. 2013;381:1107-15. https://www.ncbi.nlm.nih.gov/pubmed/23415013
  2. Fiedler KA, Maeng M, Mehilli J, et al. Duration of triple therapy in patients requiring oral anticoagulation after drug-eluting stent Implantation: The ISAR-TRIPLE Trial. J Am Coll Cardiol. 2015;65:1619-29. https://www.ncbi.nlm.nih.gov/pubmed/25908066
  3. Gibson CM, Mehran R, Bode C, et al. Prevention of bleeding in patients with atrial fibrillation undergoing PCI. N Engl J Med. 2016;375:2423-2434. http://www.nejm.org/doi/pdf/10.1056/NEJMoa1611594
  4. Cannon CP, Bhatt DL, Oldgren J, et al. Dual antithrombotic therapy with dabigatran after PCI in atrial fibrillation. N Engl J Med. Published online, Aug, 27, 2017. http://www.nejm.org/doi/pdf/10.1056/NEJMoa1708454

 

Contributed by Amulya Nagarur, MD, Mass General Hospital, Boston, MA

In my patient on oral anticoagulation about to undergo coronary stenting, will triple therapy (an oral anticoagulant plus two antiplatelet agents) be necessary or can I get away with double therapy (an oral anticoagulant plus a single antiplatelet agent)?

What pharmacological options should I consider when treating neurogenic orthostatic hypotension in my elderly patient with supine hypertension?

Treating symptomatic neurogenic orthostatic hypotension (nOH) in patients with supine hypertension can be challenging.

Before adding new agents, consider discontinuation or dose reduction of medications that can potentially aggravate orthostatic symptoms (eg, diuretics, vasodilators, negative chronotropic agents, including beta blockers).

Midodrine (an α1-adrenoreceptor agonist) and droxidopa (a norepinephrine pro-drug) are the only 2 FDA-approved drugs for the treatment of OH.

  • Midodrine is typically dosed between 2.5 mg-15 mg 1-3x/d during waking hours (prior to getting out of bed, before lunch, mid-afternoon).
  • Droxidopa is dosed from 100-600 mg 3x/day during waking hours (eg, 8 AM, noon, 4PM).
  • To reduce the risk of supine hypertension, these agents are not recommended to be taken within 5 h of bedtime, and should be used with caution in patients with congestive heart failure and chronic renal failure.

Fludrocortisone and pyridostigmine are used off-label for treatment of nOH.

  • Fludrocortisone (typical dose 0.1-0.2 mg/day) expands intravascular blood volume by increasing renal sodium and water reabsorption, with an attendant risk of exacerbating supine hypertension, hypokalemia, and edema.
  • Pyridostigmine (typical dose 30-60 mg 1-3x/day) is an acetylcholinesterase inhibitor that potentiates neurotransmission in the sympathetic ganglia and has the advantage of not worsening supine hypertension. Side effects include abdominal cramps, diarrhea, excessive sweating and urinary incontinence.

In practice,  1 or more of these agents are often used along with non-pharmacological measures.

Go to a related pearl at https://pearls4peers.com/2017/09/18/which-non-pharmacological-approaches-may-help-symptoms-of-orthostatic-hypotension-in-my-patient-with-autonomic-insufficiency/.

 

Reference

Gibbons CH, Schmidt P, Biaggioni I, et al. The recommendations of a concensus panel for the screening, diagnosis, and treatment of neurogenic orthostatic hypotension and associated supine hypertension. J Neurol 2017;264:1567-82.https://www.ncbi.nlm.nih.gov/pubmed/28050656

 

What pharmacological options should I consider when treating neurogenic orthostatic hypotension in my elderly patient with supine hypertension?

Which non-pharmacological approaches may help symptoms of orthostatic hypotension in my patient with autonomic insufficiency?

A number of simple measures to help reduce the symptoms of neurogenic orthostatic hypotension (nOH) in susceptible patients have been recommended.1

  • Blood volume repletion (a minimum of 64 oz or 2L of water intake daily), depending on cardiac status. In addition, rapid consumption (within 5 min) of 16 oz or 500 ml of water can raise blood pressure by 30 mmHg for about an hour. It’s worth noting that liquids other than water (eg, water plus salt) do not provide the same BP response, likely due to water-induced hypo-osmolar reflex in the portal circulation.2,3
  • Increase salt intake if possible (eg, add 1-2 teaspoons or 2.3-4.6 g of salt per day), as many patients with nOH have an inadequate salt intake.
  • Improve physical conditioning that is not gravitationally challenging (eg, stationary recumbent bicyle, rowing machine).
  • Avoid increased core body temperature (eg hot tubs, prolonged hot showers).
  • Head-up position while sleeping through use of a wedge under the mattress or blocks under the head of the bed so that the head is 6-9 inches (15-23 cm) higher than the feet. This is to minimize nocturnal supine hypertension which can cause pressure diuresis and volume depletion.
  • Compressive garments, preferably either an abdominal binder or thigh high stockings when erect; knee high stocking are not likely to be effective.
  • Smaller, more frequent,  meals not high in carbohydrates in patients with postprandial hypotension.
  • Dietary supplementation with B12 or iron, if deficient.

 

References

  1. Gibbons CH, Schmidt P, Biaggioni I, et al. The recommendations of a consensus panel for the screening, diagnosis, and treatment of neurogenic orthostatic hypotension and associated supine hypertension. J Neurol 2017;264:1567-1582. https://www.ncbi.nlm.nih.gov/pubmed/28050656
  2. Jordan J, Shannon JR, Black BK, et al. The pressor response to water drinking in humans: a sympathetic reflex? Circulation 101:504-9. http://circ.ahajournals.org/content/101/5/504.long
  3. Raj SR, Biaggioni I, Black BK, et al. Sodium paradoxically reduces the gastropressor response in patients with orthostatic hypotension. Hypertension 2007;48:329-334. https://www.ncbi.nlm.nih.gov/pubmed/16785332
Which non-pharmacological approaches may help symptoms of orthostatic hypotension in my patient with autonomic insufficiency?

What is the utility of urine dipstick for blood in diagnosing rhabdomyolysis?

Although the dipstick method of detecting blood in the urine is convenient, it cannot differentiate between hemoglobin, myoglobin, or red blood cells. 1

Several reviews suggest that urine myoglobin is unstable with subpar performance in rhabdomyolysis1, often defined as creatine kinase (CK) elevation 5 times the upper limit of normal in the proper context (eg, crush injury, hypoxic/ischemic or drug injury). A sensitivity of 71% and a specificity of 54% for urine hemoglobin by dipstick, and a sensitivity of 25% and specificity of 75%  for urine myoglobin  has been reported in patients with serum CK >10,000 U/L. 3  

So while a positive dipstick for blood with few or no RBCs in the urine may make us think about rhabdomyolysis, its absence should not be used to exclude it in a susceptible host.

Final fun pearl: Did you know that consumption of quail has been associated with rhabdomyolysis, possibly due to their feeding on poisonous plants such as hemlock?

References

  1. Rodriguez-Capote Karina, Balion CM, Hill SA, et al. Utility of urine myoglobin for the prediction of acute renal failure in patients with suspected rhabdomyolysis: A systematic review. Clin Chem 2009;55:2190-97. https://www.ncbi.nlm.nih.gov/pubmed/19797717
  2. Nance JR, Mammen AL. Diagnostic evaluation of rhabdomyolysis. Muscle Nerve 2015;51:793-810. https://www.ncbi.nlm.nih.gov/pubmed/25678154
  3. Grover DS, Atta MG, Eustace JA, et al. Lack of clinical utility of urine myoglobin detection by microconcentrator ultrafiltration in the diagnosis of rhabdomyolysis. Nephrol Dial Transplant 2004;19:2634-38. https://www.ncbi.nlm.nih.gov/pubmed/15280520
What is the utility of urine dipstick for blood in diagnosing rhabdomyolysis?