Monte Minute‎ > ‎Monte Minute‎ > ‎

Hypertensive Encephalopathy & Pneumocystis jirovecii Pneumonia - 10/15/2012

posted Oct 15, 2012, 11:35 AM by Rohit Das   [ updated Dec 27, 2012, 6:43 AM by Purnema Madahar ]

Hypertensive Encephalopathy at the Weiler Division, by Rohit Das

At Chief of Service last week, one of our residents presented a case of acute onset of altered cognition which, after a multitude of diagnostic tests, was of unclear etiology. He was very hypertensive at presentation, which brought up the possibility of hypertensive encephalopathy…I thought I’d talk about this interesting syndrome, and address the following questions:

·         What is the epidemiology and pathophysiology of hypertensive encephalopathy?

·         What are its clinical manifestations and value of additional diagnostic tools?

·         What is RPLS/PRES, and it’s relation to hypertensive encephalopathy?

·         What is the management for hypertensive encephalopathy, and its prognosis?

What is the epidemiology and pathophysiology of hypertensive encephalopathy?

·         In general, HTN is extremely common, affecting 20-30% of the population in developed countries. It is more common in men as compared to women. In regard to race, the incidence and prevalence is 1-2 times higher in the African-American population as compared to the white population. With improved management of HTN, the incidence of HTN related crises is rare, occurring in <1% of individuals with HTN.

·         Given that it’s a systemic illness, HTN emergency can have end-organ effects on various organ systems, including the eyes (ophthalmic exam is particularly useful in differentiating urgency from emergency), heart, kidneys, and the focus of this daily – the brain. The various manifestations are reviewed nicely in the attached Lancet article.

·         The pathophysiology of HE is related to the brain’s ability to autoregulate cerebral blood flow. Figure 2 in the Lancet article pictorially illustrates this concept. At a MAP between 60-120 mmHg, compensatory vasoconstriction/dilatation maintains the same cerebral blood flow and limits cerebral hyperperfusion. At a MAP of 150-180 mmHg (depending on whether the HTN is acute or chronic), this mechanism is overwhelmed, and cerebral vasodilatation leads to cerebral edema, and ultimately, the presentation of Hypertensive Encephalopathy.

What are the clinical manifestations and value of additional diagnostic tools?

·         Hypertensive encephalopathy generally presents insidiously, over days to weeks, with predominantly neurologic symptoms. The most common symptoms are headache and nausea/vomiting (sorry couldn’t find good numbers), followed by more generalized symptoms, like seizures, confusion, and if left untreated, coma.

·         Though basically a clinical diagnosis, imaging is of some utility, particularly to exclude important diagnoses on the differential that have a different management – e.g. ischemic stroke and intracranial hemorrhage.

·         Specifically, T2-weighted MR imaging can reveal vasogenic edema of the parieto-occiptal regions, but is certainly not exclusive (i.e., hypertensive encephalopathy can occur without these findings). Though findings are generally bilateral, asymmetric imaging findings have been reported. This brings us to our next topic…

What is RPLS/PRES, and it’s relation to hypertensive encephalopathy?

·         RPLS = Reversible Posterior Leukencephalopathy Syndrome (RPLS), and is often referred to as PRES, Brain capillary leak syndrome, and a bunch of other weird names. The term was first officially coined in 1996, characterizing a clinical syndrome similar to what’s described above, in association with characteristic neuroimaging findings of posterior cerebral white matter edema.

·         Very interestingly, from a pathophysiologic standpoint, it is thought that the predominance of edema in the posterior regions of the brain is due to a relatively deficiency (as compared to the anterior regions of the brain) of sympathetic innervation, which is responsible for cerebral autoregulation of blood flow, as described above.

·         There are several causes of RPLS, one of which is hypertensive encephalopathy. RPLS is also associated with HUS/TTP, Eclampsia, Autoimmune Diseases, and Immunomodulatory drugs (particularly Cyclosporine)…among other things (reviewed well on Table 1 of the 2006 PRES article). It’s important to realize this, as RPLS can occur in the absence of severe hypertension. In those cases, the pathology is due to direct toxic effects on vascular endothelium, from the various etiologies mentioned above.

What is the management for HE, and its prognosis?

·   Of note, there have been no randomized trials for optimal treatment of hypertensive encephalopathy and recommendations are based on consensus agreement. Generally, the goal is to decrease the MAP by no more than 20-25% within the first 2 hours, or decreasing the diastolic pressure below 100-110 mmHg over minutes-hours.

·    Ideally, management should be in an ICU setting, with arterial pressure monitoring. Regarding specific agents, Na Nitroprusside is probably the most commonly used agent. The various agents, their dose, kinetics and adverse effects are very nicely outlined in Table 2 of the Lancet article.

·    In general, the prognosis of HTN encephalopathy is very favorable, with most patients recovering within 2-3 weeks. However, prognosis has not been well studied, and risk factors for worse outcome are not well defined. Based on some studies, MR imaging suggestive of cytotoxic edema and extensive brain involvement (particularly in the brainstem) correlate with worse prognosis.

Interesting stuff...or at least I think so...I think this sheds on some light on yet another cause of altered mental status....KEEP READING!!!!! 


Hypertensive Emergencies
Vaughan et. al., Lancet 2000, Volume 356: 411-17

Mirza, J Clin Neurosci 2006, Volume 13: 590-95

Pneumocystis jirovecii pneumonia at the Moses Division, by Monique Tanna

We’ve already seen a few cases of PCP pneumonia this month on the NW floors.  This is not surprising given our sick patient population, and I think it’s a good opportunity to review this clinical condition.  Pneumocystis was first identified by Carlos Chagas in 1909 and Carinii in 1910 and mistakenly thought to be a variant of the trypanosome (1).  It was recognized as a unique organism in 1912 by Delanoe and Delanoe, and named pneumocystis carinii after Carinii.  It was uncommon and seen only in patients with malignancy, malnourishment or on immunosuppressive therapy, until the beginning of the AIDS epidemic, when its incidence rose dramatically (1).  Although the incidence of PCP is now much less given ART and PCP prophylaxis, it is still the most common opportunistic infection in HIV-infected patients (3).

What is pneumocystis and what is its official name?

First identified as a protozoan, pneumocystis was reclassified as a fungus in 1988 (2).  There are four species of pneumocystis, including P. carinii which infects rats, and P. jirovecii which infects humans.  The official name is pneumocystis jirovecii, although many still use the abbreviation “PCP” to refer to “PneumoCystis Pneumonia” (3). 

What are the clinical and radiographic manifestations of PCP?

PCP pneumonia in HIV patients presents with a subacute or gradual onset, and 7% of patients may be asymptomatic (3).  Common symptoms include fever (79-100%), cough (95%; usually nonproductive but may be productive in up to 30%), and progressive dyspnea (95%) (3).  Other nonspecific symptoms include fatigue, chills, chest pain, and weight loss (3).   The most common physical exam findings are fever (84%) and tachypnea (62%).  The lung exam may be notable for crackles and rhonchi, or may be normal in 50%.  Assessing the patient’s oxygenation at rest and with exercise is also useful, and if normal makes PCP very unlikely (3).  Similarly, a normal DLCO (>70%) also makes PCP unlikely. 

Chest xray is initially normal in up to 25%, or may show diffuse, bilateral, interstitial, or alveolar infiltrates (3).  Typical features are bilateral perihilar interstitial infiltrates which become diffuse and homogenous as the condition progresses (2).  CT scans have greater sensitivity and may show extensive ground-glass attenuation or cystic lesions (2). 

What labs do I need to check?

In any patient with HIV and a clinical presentation suggestive of PCP, it is vital to check the current CD4 count even if it was previously above 200.  In the multicenter AIDS Cohort Study, the incidence of PCP in patients with a CD4 count of 201-350 was 0.5%, while in patients whose CD4 count decreased to <200, 8% developed PCP within 6 months (3).  An elevated LDH is present in 90% of HIV patients with PCP and correlates with prognosis (3).  A rising LDH despite treatment also correlates with worse prognosis.  The patient’s oxygenation must also be assessed, as it will determine whether steroids are indicated (see below).

How is PCP diagnosed?

Although it is important to diagnose PCP, it should be suspected clinically and empiric treatment should be started while diagnostic studies are pending.  PCP is detected microscopically in sputum, bronchoalveolar fluid, or lung tissue since it cannot be cultured.  Sputum induction with hypertonic saline has a diagnostic yield of 50-90% (2) and is rapid and least invasive.  While its specificity is nearly 100%, the sensitivity ranges from 55-92% and depends on the disease prevalence, skill of those collecting sputum, and laboratory expertise.  Bronchoalveolar lavage in HIV patients has a diagnostic yield of 97-100% (3).  Patients with PCP also have higher 1-3-beta-D-glucan levels, and the sensitivity of this test for diagnosis of PCP is 92% with a specificity of 65% (3).

How is PCP treated and when should I give steroids?

A 21 day course of TMP-SMX (2 DS tabs q8 hours) is the preferred regimen, and can be given orally in mild to moderate disease if the patient is able to tolerate po meds.  If the patient is severely ill, with a PaO2 < 70, or unable to take po, s/he should be given IV TMP-SMX with a prednisone taper.  Patients typically worsen after 2-3 days of therapy, presumably due to inflammation caused by the dying organisms.  Steroids can decrease mortality and respiratory failure in severe cases of PCP and should be given to any patient with a room air PaO2 ≤ 70 mm Hg or A-a gradient ≥ 35 mm Hg.  Worsening respiratory status in a patient being treated for PCP is also an indication for steroids even if s/he did not meet these initial criteria.  Alternatives to TMP-SMX include pentamidine, atovaquone, TMP+dapsone, and primaquine+clindamycin.

Who should receive prophylaxis?

Primary prophylaxis should be given to any HIV-infected patient with a CD4 count < 200.  Patients with a history of esophageal candidiasis who are not on ART should also receive PCP prophylaxis.  Secondary prophylaxis should be given to anyone with a history of PCP and continued lifelong unless they have a reconstitution of their immune system with ART.  Prophylaxis can be discontinued if a patient’s CD4 count increases to >200 for >3 months, but should be resumed if the CD4 count falls again or if the patient develops PCP despite a CD4 count >200. 

What is the prognosis, before and after the advent of ART?

Patients can worsen clinically on day 2-3 of treatment with an increased A-a gradient, presumably due to inflammation caused by dying organisms, but should begin to improve by day 5 of therapy (4).   

One study showed that the mortality from PCP decreased from 21% to 7% between 1986 and 2005 with the use PCP prophylaxis and ART (3).  Other studies have shown that PCP is still a leading cause of death among patients noncompliant with ART or PCP prophylaxis (3).  Older age, recent IVDU, elevated total bilirubin, low albumin, elevated LDH, low CD4 count, and an A-a gradient >50 mm Hg are all predictors of mortality (3,4). 

References:

1. PCP Review 1997
Santamauro JT, Stover DE. Pneumocystis carinii pneumonia. Medical Clinics of North America. 1997 Mar;81(2):299-318.

2. PCP Review NEJM 2004
Thomas CF Jr, Limper AH. Pneumocystis pneumonia. N Engl J Med. 2004 Jun 10;350(24):2487-98.

3. Tietjen PA. Clinical presentation and diagnosis of Pneumocystis infection in HIV-infected patients. In: UpToDate, Bartlett JG (Ed), UpToDate, Waltham, MA, 2012.

4. Sax PE, Tietjen PA. Treatment of Pneumocystis infection in HIV-infected patients. In: UpToDate, Bartlett JG (Ed), UpToDate, Waltham, MA, 2012.

Additional Reading:

PCP in HIV JAMA 2001
Kovacs JA, Gill VJ, Meshnick S, Masur H. New insights into transmission, diagnosis, and drug treatment of Pneumocystis carinii pneumonia. JAMA. 2001 Nov 21;286(19):2450-60.

PCP in Immunosuppressed JAMA 2009
Kovacs JA, Masur H. Evolving health effects of Pneumocystis: one hundred years of progress in diagnosis and treatment. JAMA. 2009 Jun 24;301(24):2578-85.

Comments