Nephrolithiasis, “Answers”

Posted on May 19, 2012 by

1. What is your preferred pain regimen in acute renal colic?  What do you like to give for home pain control?

Many consider NSAIDs to be first-line for renal colic pain, as they directly affect the ureter, inhibiting the synthesis of prostaglandins. A  prospective, double-blinded, placebo-controlled RCT from 2006, however, found that morphine plus ketorolac provided superior pain relief when compared to morphine alone, and decreased the incidence of vomiting (Safdar, 2006).   A 2005 Cochrane review showed that both NSAIDs or opiates reduced pain in acute renal colic, and that NSAIDs had a more favorable side effect profile (Holdgate, 2005).

Most emergency physicians seem to prefer a combination approach of ketorolac (Toradol) (or other NSAID if the patient can tolerate PO) with an opiate agent (typically morphine or hydromorphone).  These drugs are often paired with an anti-emetic, as renal colic can cause a significant amount of nausea.  One common regimen for an adult is ketorolac 30 mg IV (or 60 mg IM)+ morphine 0.1 mg/kg IV + metoclopramide 10 mg IV.  Interestingly, metoclopramide is one of the few anti-emetics that has been studied with regards to renal colic; some small series suggest it also aids in pain relief on its own, and is less sedating than others in its class (Muller, 1990).

It is important to note that parenteral (neither IV nor IM) ketorolac has never really been shown to be superior to oral ibuprofen in terms of pain relief or time of onset to pain relief. If the patient is tolerating PO, ibuprofen is an appropriate substitute.

The prior dogma of forced IV hydration does not improve pain, or increase the rate of stone passage, and may, in fact, worsen pain in cases of obstruction (Springhart, 2006). A few studies have tried intranasal desmopressin, for its antidiuretic properties, and have found it to decrease pain in acute renal colic (Roshani, 2010), although not widely employed in practice.

For home pain control, following a combination method of attack is common as well.  Most patients are discharged on a short course of NSAIDs (ibuprofen 400 – 600 mg PO Q8) + an opiate/acetaminophen combination drug (oxycodone/APAP or hydrocodone/APAP) for breakthrough pain.

2. When do you use ED ultrasound?  If it shows hydronephrosis, how does this affect your management?

The issue of when and how to employ ultrasound in a patient with presumed (or known) renal colic requires restatement of the goals of ED management.  With the growing literature demonstrating the risks of ionizing radiation, CT scanning should be avoided where possible.  An ultrasound coupled with a good history and physical examination along with a urinalysis (looking for infection) may obviate the need for a CT scan to attain diagnostic certainty in the right patient population, namely the young and otherwise healthy in whom your suspicion of renal colic is very high (especially those with a history of same). For more on the question of whether or not to employ CT, and the necessity of definitive diagnosis, please also see question four.

Ultrasound in renal colic can involve attempting to visualize the stone, and/or evaluate for unilateral hydronephrosis.  With regards to the former, ultrasound has only modest sensitivity, 60-80%, depending on operator and patient characteristics, and does poorly with small stones (<5mm), obese patients, and mid-ureteral stones.  This sensitivity, when compared to the 97-99% sensitivity of CT in detecting stones, makes ultrasound seem questionable as a diagnostic modality for visualizing renal stones.  In terms of hydronephrosis, however, ultrasound has a sensitivity around 92%,  (Sheafor, 2000), a respectable level seen in numerous series on the topic. It is worth mentioning that some radiologists and ultrasonographers believe the false negative rate for hydronephrosis on renal ultrasound to be has high as 22% (Koelliker, 1997) due to anatomic variants, full bladder, etc.. It is in answering the question of whether or not hydronephrosis is present that most emergency physicians employ a bedside renal ultrasound (Noble, 2004).

The presence of a history, physical and urinalysis consistent with nephrolithiasis in a young (most experts arbitrarily say <50) otherwise healthy patient (no underlying renal disease, normal renal function), coupled with the absence of other complications (infection, acute kidney injury, etc.), even with an ultrasound showing hydronephrosis, is still often sent home with Urology follow up in less than one week. Which is to say that even patients with a complete obstruction do not necessarily require emergent decompression of their nephrolithiasis. Some emergency physicians use the presence or absence of hydronephrosis on a bedside ultrasound to risk stratify the time to  follow-up and the need to discuss the case with a urologist prior to discharge. There is also a precedent for combining a bedside ultrasound showing hydronephrosis with clinical gestalt to enhance the predicted likelihood of a diagnosis of nephrolithiasis by emergency physicians (Rosen, 1998).

3. Do you give alpha-blockers to aid stone expulsion (tamsulosin or terazosin)?

In 2007, the best studies on this treatment modality were collected and published in a systematic review (Singh, 2007).  The conclusion of this systematic review was that the use of alpha-blockers increased the rate of passage of moderately-sized, distal ureteral stones.  However, the sixteen studies reviewed were not high quality (none were randomized, none were double-blinded) and the authors stated that further research should be done to confirm their conclusions.

Since then, two studies have found no benefit to tamsulosin for treatment of renal colic.  Ferre, et al., 2009,  published a randomized, controlled trial 0f 80 subjects which did not show a difference in spontaneous stone passage at fourteen days, time to passage of stone (average stone size 3.6 mm), pain, return ED visits, or adverse outcomes.  This was the first published, randomized trial and the first published trial of ED patients.

In December 2010, a multicenter, placebo-controlled, randomized, double-blind study was published in Archives of Internal Medicine, comparing tamsulosin to placebo (Vincendeau, 2010).  This study  was also performed on ED patients.  This trial concluded that tamsulosin did not decrease the time to stone passage (primary endpoint), use of pain medications, or the rate of surgical procedures (secondary endpoints).  One caveat to this study was that the vast majority of stones were < 3 mm and some experts contend that tamsulosin may have its greatest benefit in stones > 5 mm. The controversy continues in the Urology literature with some RDCTs amongst clinic patients showing a benefit (Abdel-Mequid, 2010; Al-Ansari, 2010) and others showing none (Hermanns, 2009; Agrawal, 2009).  Many, if not most, of our urology colleagues continue to use alpha-blockers for nephrolithiasis, although this practice does not appear to be well-supported by the recent literature, with the bulk of studies showing no effect, especially in ED patients.

4.  Who do you CT?  Who do you not CT?

Helical CT has become the diagnostic modality of choice in urolithiasis in the last ten years because of its high sensitivity (97%) and specificity (96%) (Sheafor, 2000).  In addition to diagnosis, CT provides a great deal of additional information about kidney stones including size, location, presence or absence of hydronephrosis, density of the stone (Hounsfield units) to help determine best treatment options, other complicating issues associated with nephrolithiasis, and other diagnoses if nephrolithiasis is not present.

Many emergency physicians scan all adult patients on their first presentation of unilateral flank pain, presumed to be renal colic. This practice is potentially supported by a small Canadian series that looked at 132 patients and examined the effects of CT scan on diagnosis and disposition, grouped by pre-test likelihood. In 40 of the cases (33%) CT revealed alternate pathology, including 19 with very high pre-test likelihood of a nephrolithiasis diagnosis according to their physician in whom significant other pathology was found (lymphoma, AAA, metastases, undiagnosed malignancies, etc.) (Ha, 2004). This study, and others like it, are a sobering reminder of significant diagnostic uncertainty in the patient with a first episode of unilateral flank pain.

Some commentators, however, feel it is reasonable in a young person with a classic presentation to get an renal ultrasound (and possibly an ultrasound of the abdominal aorta while in the neighborhood, and/or a KUB, although sensitivity is quite low, around 50-60% even for radiopaque stones) and make a diagnosis based on the clinical picture and ultrasound findings, deferring definitive imaging to an outpatient setting, or if a return ED visit is required due to clinical course.

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Nephrolithiasis, Questions

Posted on May 2, 2012 by

1. What is your preferred pain regimen in acute renal colic?  What do you like to give for home pain control?

2. When do you use ED ultrasound?  If it shows hydronephrosis, how does this affect your management?

3. Do you give alpha-blockers to aid stone expulsion (tamsulosin or terazosin)?

4.  Which patients do you CT?  Which patients do you not CT?

Nephrolithiasis Questions Poster

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Hyperkalemia, “Answers”

Posted on April 18, 2012 by

1)    What are the EKG manifestations associated with hyperkalemia?  Do these changes occur in a predictable order?

Hyperkalemia is one of the most lethal and treatable metabolic disturbances faced by emergency physicians.  Therefore, its rapid recognition and treatment is paramount to the survival of the critically ill patient.  Oftentimes, the EKG is utilized to assist in its early identification at the bedside, before lab results return.

Classically, it has been taught that there is a step-wise progression of EKG changes that occur in patients as their serum potassium level rises.  Initially the EKG change begins with peaked T-waves in mild hyperkalemia (<6.5mEq/L). As the serum concentration of potassium increases, conduction from one cardiac myocyte to the next is impaired, resulting in increases in the PR intervals, flattening/disappearance of the p-waves, and then widening of the QRS with moderate hyperkalemia (6.5-8.0mEq/L).  Finally, as serum potassium continues to rise, there is further widening of the QRS until it merges with the T-wave producing the classic “sine-wave” pattern on EKG; eventually ventricular fibrillation or asystole ensues in severe hyperkalemia (>8.0mEq/L).

Although there is evidence in the medical literature that this pattern does exist, some studies have shown that when EKG changes occur, they may not progress in the expected step-wise fashion. Patients may progress from normal sinus rhythm to ventricular fibrillation as their first EKG manifestation of hyperkalemia (Dodge, 1953).  In addition to the classic EKG findings of hyperkalemia, elevated potassium levels may also manifest as sinus bradycardia, right or left bundle branch blocks, and 2nd and 3rd degree AV blocks.

Not only is progression of EKG changes unpredictable in hyperkalemia, the EKG is also not a very sensitive indicator of hyperkalemia.  In a retrospective review of 90 patients with mild-moderate hyperkalemia (80% with serum potassium levels < 7.2mEq/L) only 18% met strict criteria and only 52% met any criteria for EKG abnormalities associated with hyperkalemia (Montague, 2008).  Although studies demonstrate that the probability of having EKG changes increases as the serum potassium level rises, there are case reports of patients with extremely severe hyperkalemia (>9.0mEq/L) that still did not demonstrate any of the predicted EKG manifestations (Szerlip 1986).

Some evidence shows that instead of the absolute serum potassium concentration, there may be a higher likelihood of EKG changes when rapid rises in serum potassium concentration occur (Fisch, 1973 & Surawicz, 1967).

Therefore, the EKG is a not a marker of how sick a patient may be with regards to their potassium level.  Have a low threshold to treat a patient with hyperkalemia, whether or not their EKG shows classic manifestations.  Do not to feel a false sense of security with a lack of EKG findings in these patients, and understand that the patient’s EKG may change rapidly into a lethal arrhythmia.

2)    What is the role of Kayexalate in the treatment of hyperkalemia?

Kayexalate (Sodium Polystyrene Sulfate) is a cation-exchange resin that was approved in 1958 as a treatment for hyperkalemia by helping to exchange sodium for potassium in the colon and thus excreting potassium from the body.  Although this drug has been used for a numbers of years as an adjunct to more acute treatments, there are two potential problems with its use.

Firstly, there is little to no evidence that Kayexalate effectively reduces serum potassium levels.  The two original studies promoting its use, often cited in literature, were published in the New England Journal of Medicine in 1961.  The methodology of these two trials was completed without any controls, included multiple confounding variables, a lack of rigorous statistical analysis, and demonstrated minimal if any effect of Kayexalate on serum potassium levels (Scherr, 1961 & Flinn, 1961).  Furthermore, a 1998 study also failed to demonstrate a statistically significant difference in serum potassium levels at 4, 8, and 12 hrs after administration of 30g Kayexalate with sorbitol compared to placebo controls (Gruy-Kapral, 1998).

In addition to the lack of evidence demonstrating any efficacy, there have been multiple case reports of intestinal necrosis, GI bleeding, and intestinal perforation secondary to Kayexalate (Rogers, 2001 & Rashid 1997).  In 2009 the FDA responded to these case reports by placing a warning on Kayexalate for these effects.  The warning stated that the complications were primarily seen in patients who received Kayexalate along with sorbitol, and deemed sorbitol to be the primary culprit.  Most Kayexalate preparations carried by hospitals, however, have sorbitol already mixed into them, as the powdered version of Kayexalate alone is not easily available.

Due to the lack of literature showing any benefit of Kayexalate in decreasing serum potassium levels, as well as reports of serious side effects associated with its usage, including intestinal necrosis, Kayexalate should play little, if any, role in the treatment of hyperkalemia in the emergency department and upon admission to other hospital services.

3)    Is there a threshold serum potassium level or particular EKG finding that triggers you to administer calcium?  How do you give calcium when you use it?

Generally, calcium is administered to hyperkalemic patients to stabilize the cardiac myocytes by restoring their normal resting membrane potential (Fisch, 1973).  It is generally reserved for moderate to severely hyperkalemic patients with cardiac instability.  Although there are no clear guidelines or evidence demonstrating the exact point to administer calcium, many clinicians will administer it if: (1) the EKG shows evidence of cardiac destabilization such as widening QRS or loss of p-waves on EKG (N.B.: As discussed in question 1, EKG findings in patients with hyperkalemia can vary from patient to patient, and patients with severely elevated serum potassium levels may not manifest concomitant EKG findings);  (2) Serum potassium levels above 6.5-7mEq/L regardless of the presence of EKG changes; or (3) rapid rises in serum potassium levels.  As a general rule, however, have a low threshold to administer calcium.

There are two options when administering calcium: calcium gluconate and calcium chloride.  Both types of calcium work relatively quickly in restabilizing the cardiac myocyte membrane, within 3-5 minutes.  Calcium chloride contains three times the concentration of calcium compared to calcium gluconate.  Therefore, 1gm of calcium chloride is approximately equivalent to 3gm of Calcium gluconate. Calcium chloride does not need metabolism by the liver in order to be bioavailable to cardiac myocytes, and thus is the preferred method of administration in patients with liver failure, cardiac arrest, or in shock states.  Calcium chloride, however, does pose a very serious risk for the development of tissue necrosis if it extravasates into the surrounding tissue (Semple, 1996).  Therefore, it must be administered via a central venous line or a large bore, well-placed peripheral line.  Calcium gluconate, however, can be administered through a small peripheral IV if needed, as its risk of tissue necrosis is much less.  Patients should be on a cardiac monitor when receiving calcium infusions.

4)    When do you re-dose patients?

When treating patients with hyperkalemia, we often forget to re-dose patients after their initial treatment is given.  In terms of calcium, a second dose can be administered after about 5 minutes if EKG changes persist or worsen.  Although its effect is quite rapid (within 3-5 minutes), it only stabilizes the cardiac myocytes for approximately 30-60 minutes (Weisberg, 2008).  After this time, a repeat EKG may be necessary, along with a repeat serum potassium level, and an additional dose of calcium.

In terms of albuterol, if the appropriate dose of 20mg (nebulized) is given, its effect usually lasts for approximately 2 hours after which time it may require re-dosing.  Note that the dose to treat hyperkalemia is approximately four times the amount normally given to an asthmatic or patient with emphysema for respiratory complaints.

Insulin is normally administered as a 10 Unit IV bolus along with 1-2 amps of D50.  When given as an IV bolus, the intracellular effects of insulin will last for approximately 4-6 hours after which it may need to be re-dosed.

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Hyperkalemia, Questions

Posted on March 22, 2012 by

1.    What are the EKG manifestations associated with hyperkalemia?  Do these changes occur in a particular order?

2.    What is the role of Kayexalate in the treatment of hyperkalemia?

3.    Is there a threshold serum potassium level or particular EKG finding that triggers you to administer calcium?  How do you give calcium when you use it?

4.    When do you re-dose patients you’ve treated for hyperkalemia?

Hyperkalemia Questions Poster

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Viral Meningitis, “Answers”

Posted on March 2, 2012 by

1.  Are there any elements on history & physical that make you suspect viral meningitis in adult patients? Do you LP all patients you suspect have viral meningitis?

Clinicians have long tried to identify elements of a patient’s history or physical examination that may help rule-out a diagnosis of meningitis–viral or otherwise–so as to spare patients an unnecessary lumbar puncture.  This has not proven to be an easy task, and unfortunately seems to be an unrealistic goal.

In one JAMA analysis of multiple studies, the complaints of headache and nausea/vomiting were found to have pooled sensitivities/specificities of only 50%/50% and 38%/60%, respectively. The same review found that the physical exam findings were slightly more helpful: fever had the highest sensitivity (85%), while neck stiffness had the next highest (70%).  Perhaps the most helpful finding was that 95% of patients who had meningitis had at least two of the classic findings of fever, neck stiffness, and altered mental status/headache, and that 99-100% had at least one such finding.  The absence of all of those complaints may effectively rule out meningitis (Attia, 1999).

The classically described Kernig and Brudzinski signs are not at all sensitive for the diagnosis of meningitis (~5-30%) but have relatively high specificities (70-100%) (Waghdhare, 2010; Uchihara, 1991; Thomas, 2002). Thus the presence of these symptoms should substantially increase a clinician’s suspicion for the presence of meningitis.

Lastly, the jolt accentuation test has had mixed findings. One prospective study found it to be 87% sensitive and 60% specific (Uchihara, 1991), but another more recent study has found almost the reverse, with a very low sensitivity (6%) and a high specificity (98%). (Waghdhare, 2010).

Duration of symptoms may be tempting to use as a means of ruling out bacterial meningitis, given that this disease is often rapidly fatal. Hence a complaint of severe headache for over a week seems to rule out this serious entity.  However, studies have not looked at this is as valid means of differentiating between bacterial and viral meningitis, and perhaps more importantly, some aseptic meningitides that require immediate treatment, such as cryptococcal meningitis or tuberculous meningitis, are typically subacute in onset.

In summary then, clinical signs and symptoms have very low yield in ruling out a diagnosis of meningitis, leave alone differentiating between viral and bacterial meningitis.  Therefore, in the absence of any contraindication, an LP should always be performed in patients in whom meningitis is suspected on clinical grounds (Viallon, 2011; Tunkel, 2004).

2.  Does a “normal” CSF reassure you that the patient does not have bacterial meningitis?

There are actually two important questions to ask here: 1) Does an entirely normal CSF, with negative gram stain, rule out bacterial meningitis (BM)? and 2) How useful are standard CSF parameters (cell count with differential, glucose, protein, and gram stain) in differentiating between bacterial and aseptic meningitis?

Regarding the first question it is very rare, but not unheard of, to have completely normal CSF results in the setting of acute bacterial meningitis. There are several case reports, and a few studies and reviews that describe such instances (Ray, B, 2009; Coll, 1994; Polk, 1987; Onorato, 1980). Most of them involve infants and young children, not adults. The bacteria most commonly isolated were N. meningitides, H. influenzae, and S. pneumonia.  In two pediatric studies, the incidence of BM with negative initial CSF was found to be 2.7% (Polk, 1987) and 10% (Coll, 1994).  The risk of a false-negative CSF is increased if the lumbar puncture is performed within 24 hours of onset of symptoms. If meningitis is clinically suspected, a repeat LP should be performed within 24-48 hours (Ray, B, 2009). Most reassuring is that almost all of the patients described in the various case reports and studies were either neonates, had a concerning rash, and/or were delirious or otherwise acutely ill, i.e. patients who would have been (and were) admitted and empirically treated irrespective of CSF findings.  In sum, in a non-toxic appearing, immunocompetent adult a completely normal CSF (including normal opening pressures) is highly reassuring in ruling-out bacterial meningitis, especially if the symptoms began more than 24 hours earlier.

But, what if your patient’s CSF is not entirely normal, but instead seems to suggest a viral meningitis? That is, it has a mild lymphocyte-predominant pleocytosis, a normal glucose and protein, and a negative gram stain.  Can you reassure your patient that he does not have bacterial meningitis? Unfortunately not.  While high WBC count ( >1500/mm^3), a very low glucose ( < 35 mg/dL) , a markedly elevated protein (>2.2g/L or 220 mg/dL) and/or a positive gram stain are highly suggestive of bacterial meningitis, more moderate values do not rule it out.

Several studies have shown that BM may present with CSF lymphocytosis in 15-30% of cases, especially when the WBC concentration is less than 1000/mm^3 (Lindquist, 1988; Spanos, 1989). Conversely, early viral meningitis may have PMNs predominate up to 40-50% of the time (Spanos, 1989; Archimbaud, 2009).  Glucose, protein and CSF/blood glucose ratio have also been evaluated; while some studies have found some predictive value in the glucose ratio and in CSF protein, none of these parameters has been shown to allow definite differentiation between bacterial and viral meningitis (Lindquist, 1988; Spanos, 1989).   In fact, in the original studies on CSF glucose, it was found that CSF glucose was decreased in roughly half the patients with BM.

Gram stains, while providing a definitive diagnosis of BM when positive, have also been shown to be negative in 20-40% of BM cases (Ray, P, 2007; Spanos, 1989; Viallon, 2011). In a prospective trial of adult ED patients with acute meningitis but negative gram stains, the most common bacteria identified were S. pneumoniae, L. monocytogenes, and N. meningitides.  Listeria species, in particular, have been found to be more likely to have negative gram stains (Hussein, 2000; Elmore, 1996).  Other pathogens that typically have a concentration below the diagnostic sensitivity of standard microbiologic stains include M. tuberculosis and Cryptococcus neoformans (Elmore, 1996). Therefore, in patients at risk for these pathogens (whether due to age, an immunocompromised state, travel, or other exposure history), one should consider these entities in the setting of a negative gram stain.

Bottom line: While CSF findings can be used to rule in bacterial meningitis in adult patients, they cannot be reliably used to differentiate between bacterial and viral meningitis.  Interestingly, several clinical decision rules that incorporate CSF findings have been established to help with this differentiation in the pediatric population, and one in particular (Bacterial Meningitis Score) has been retrospectively validated in several studies (Nigrovic, 2007; Dubos, 2006).  Unfortunately, no similar rule has been established and validated in the adult setting.

3.     Do you use CSF lactate or other cytochemical markers to differentiate between aseptic and bacterial meningitis?  Do you send anything beyond a standard meningitis panel for immunocompetent patients? When and what?

Given the lackluster performance of standard CSF parameters in differentiating viral and bacterial meningitis, many have sought other blood and CSF parameters to test.

Two of the most commonly studied parameters are serum procalcitonin (PCT) levels and CSF lactate.  While procalcitonin has been studied amply in the pediatric population, where it has been found to help discriminate between bacterial and non-bacterial meningitis, it has not been as thoroughly investigated in adults. One recent prospective study in adults by Viallon, et al., did show it to be highly discriminative between bacterial and viral meningitis. It found that at a level of 0.28 ng/mL, PCT was 97% sensitive and 100% specific for bacterial meningitis.  While other studies have also found PCT to be helpful, they used different cut-off levels and had less reassuring sensitivities and specificities (Schwarz, 2000; Jereb, 2001).

CSF Lactate has been more extensively investigated in the adult population.  Viallon, et al.’s study found it to have a sensitivity of 94% and specificity of 97% at a cut-off level of 3.8 mmol/L (34mg/dL). Two recent meta-analyses of 25 and 33 studies respectively have supported the usefulness of CSF lactate in this context as well. Sakushima, et al. (2011) found lactate to have a pooled sensitivity and specificity of 93% and 96%, with 3.9mmol/L (35 mg/dL) found to be the optimal cut-off.   It appeared useful in ruling out BM and in distinguishing between bacterial and viral meningitis when used in combination with other CSF characteristics, but it was also noted that pretreatment with antibiotics reduced its clinical accuracy. Huy, et al. (2010) found CSF lactate to have an excellent level of overall accuracy in differentiating bacterial and non-bacterial meningitis, with an area under the curve of 0.9840. They considered it to be a good single indicator, and a better marker compared to other conventional markers as discussed above, especially when the assay was positive (above the cut-off point defined).

Outside of the standard CSF panel, lactate and PCT, there are other studies one might consider sending to help elucidate the pathogen. As non-polio enteroviruses are the most common cause of acute viral meningitis (VM), sending an enterovirus (EV) PCR can be the quickest way to potentially rule in a viral etiology, thereby ruling out BM.  Several studies have shown that if quick turnaround times are available for EV-PCR hospital length-of-stay, and duration of antibiotics is minimized (Archimbauld, 2009; Tattevin, 2002).  HSV and viral cultures can also be sent, but will not be helpful in early differentiation, as they are less reliable than PCR, and also take up to ten days to be finalized. Latex agglutination tests can also help rule out bacterial causes of meningitis such as N. meningitides and H. Influenzae.  Whether to send other studies depends on the suspicion of specific etiologies based on clinical findings and history of possible exposures, recent/current rashes, travel history, sexual history, etc.  If the patient is altered at all and encephalitis is suspected, a broader encephalitis panel (including HSV, VZV, West Nile and others) may be sent for PCR analysis.   Other studies can include acid-fast stain and tuberculosis PCR/Culture,  VDRL, and antigen testing for cryptococcus.  HIV and Lyme disease testing may also be appropriate in patients with suspected viral meningitis.

In summary, CSF lactate may prove helpful in distinguishing bacterial from viral meningitis, especially when considered together with other CSF findings. Serum procalcitonin, while possibly helpful, is less well studied in adults.  EV PCR, where available, should be sent in patients suspected of viral meningitis. Other studies will largely depend on risk factors and presentation as assessed by the clinician.

4.  When do you admit a patient, post-LP, who appears to have viral meningitis? What anti-microbial agents do you administer these patients, if any?

There are no studies analyzing the ideal disposition of patients with suspected viral meningitis.  Traditional teaching states that patients at the extremes of age or with more severe disease, immunocompromise, suspicion of HSV or VZV meningitis, or potential nonviral causes should be hospitalized (Rosen’s, 6th ed.).  Some clinicians handle patients with classic presentations of viral meningitis as outpatients with follow-up within 24 hours, while others admit them until cultures are finalized as negative. Given the demonstrated difficulty in ruling out bacterial meningitis, this approach is understandable.

One study that evaluated the management of 168 patients who presented to the ED and were diagnosed with acute meningitis with a negative gram stain, found that 70% were admitted, 49% had cranial imaging (73% with normal findings) and 52% were treated with empiric antibiotics. Ultimately only 17% had established infectious causative agents that would have benefited from antibiotic treatment (Elmore, 1996). There were no deaths within one month of presentation. The authors conclude that better tests/clinical decision rules are needed to avoid unnecessary hospitalizations and associated costs.

Anti-microbial agent use varies similarly: some practitioners choose to cover patients with both antibiotic and antiviral agents until either bacterial cultures are negative, or a viral PCR returns with a positive result. Others who have low suspicion for bacterial meningitis may not use any antimicrobial agents or may choose to use only acyclovir. There are no studies to direct the empiric treatment of these patients.  The decision often comes down to the clinician’s assessment of the risk of either BM or HSV/VZV meningitis, with similar risk factors as those listed above for hospitalization taken into consideration. In a well-appearing, immunocompetent, young- to middle-aged adult with suspected viral meningitis, the decision of whether to admit the patient and whether to treat with empiric antibiotics and/or anti-viral agents is largely up to the clinician.  Admission is perfectly reasonable.  If the decision is made to send a patient home after a candid discussion with the patient about the potential risks is had, it is imperative that he/she be re-evaluated by a clinician within 24 hours.  Close follow-up is critical.

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Viral Meningitis, Questions

Posted on February 1, 2012 by

1.)  Are there any elements on H&P that make you suspect viral meningitis in adult patients? Do you LP all patients you suspect have viral meningitis?

2.)  Does a “normal” CSF reassure you that the patient does not have bacterial meningitis?

3.)  Do you use CSF lactate or other cytochemical markers to differentiate between viral and bacterial meningitis?  Do you send anything beyond a standard meningitis panel for immunocompetent patients? When and what?

4.)  When do you admit a patient, post-LP, who appears to have viral meningitis? What anti-microbial agents do you administer these patients, if any?

Viral Meningitis Questions Poster

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Anaphylaxis, “Answers”

Posted on January 8, 2012 by

1. How do you define anaphylaxis?  When and how do you give a patient with anaphylaxis epinephrine? How does age or past medical history factor in your decision?

Anaphylaxis is an allergic reaction, with rapid onset after contact with the offending allergen, which may cause death.  In short, the criteria for this clinical diagnosis are acute onset of skin/mucosal involvement (seen in 80-90% of patients, not all) with respiratory compromise and/or reduced blood pressure (Sampson, 2006).

There are basically no modern, placebo-controlled, randomized trials for any therapies we use for humans experiencing anaphylaxis. This is in part because of the life-threatening nature of the disease, the sense from case series and clinical practice that epinephrine works, and the difficulty of obtaining consent from a hypotensive patient in respiratory distress who is also vomiting (Sheikh, 2009).

Patients with anaphylaxis should get epinephrine now, not later. Cases series of 13, and 124, respectively, fatal and near fatal anaphylactic reactions (Sampson, 1992; Bock, 2001) showed that patients who received epinephrine within thirty minutes of symptoms were more likely to live, and that of patients who died, very few received any epinephrine during their treatment.

The method of administering epi is clear: intramuscular injection into the antero-lateral thigh. Studies in children and adults not experiencing anaphylaxis (n.b.) have shown a more rapid increase in plasma and tissue epi levels with this mode, even over IM deltoid injection (Simons 2001; Simons, 1998).

There are NO absolute contraindications to the use of epinephrine in anaphylaxis. Many practitioners are concerned about side effects of administering epi in the elderly, especially those with CAD or cardiac risk factors. Remember, however, that the heart is a target in anaphylaxis itself, which can worsen CAD, can cause MI, or cause dysrhythmia. Most experts feel this cardiac risk from untreated anaphylaxis, coupled with the risk or death or other serious illness from anaphylaxis, mean that epinephrine’s benefits outweigh this theoretical risk, and give it in such a situation (Sheikh, 2009).

2. When do you consult ENT to scope a patient with an allergic reaction/anaphylaxis?

The literature does not really address this question. Our practice is that ENT should be called early when there is any question of airway involvement, obviously with stridor, uvular or other apparent airway edema, voice changes, and so on.  However, the time course of anaphylaxis is such that by the time a consultant arrives with their scope the situation may have progressed to where you are sweating and looking at the cric kit.  All of this is to say:  call ENT early, as their visualization of the cords when airway involvement is equivocal is of utility, as are serial viewings to see edema resolving.  In the scenario of progression, especially after IM epi, however, please proceed to question three.

3. How do you make the decision to intubate a patient with anaphylaxis?

In a word, early. If you’ve never seen severe and progressive anaphylaxis, please believe us when we say you should always have a difficult airway box at the bedside and ready whenever anyone with even a hint of respiratory involvement comes to you. Over seconds to minutes, patients can go from phonating with slight voice change to complete occlusion of the upper airway with severe bronchospasm.  Be ready to cric or perform a trach, emergently.   Also, in cases such as these, when patients are not responsive to IM epi, an epinephrine drip is indicated.  Although this is slightly beyond the purview of this EM Lyceum topic, we like this video for how to make your own epi drip (in a pinch).

4. Which patients do you admit?  How long do you observe the patients you intend to discharge?

Any patient with refractory anaphylaxis or who required respiratory intervention should be admitted, without passing go, to the ICU.  For the majority of patients, though, the disposition question is one of observation time. Other factors in determining disposition are the feasibility of getting an Epi-pen at the time of discharge (e.g., pharmacy access in the middle of the night), ease of returning to the ED if there is a recurrence of symptoms, and history of biphasic anaphylaxis.

Biphasic reactions are a common concern, wherein the symptoms recur after the initial medications have worn off, or due to a second wave of immune response to an allergen. This phenomenon has been described from 1 hour to 3 days after initial exposure to the allergen (Douglas, 1994), a fact that must be communicated to patients discharged to home. From case series, it is theorized that biphasic anaphylaxis occurs in 1-20% of all cases, and that it is closer to 20% in the more severe cases, especially those requiring higher doses of epi. The expert consensus on anaphylaxis, and the practice of most physicians in our departments, is to observe patients who are symptom free for a period of 4-6 hours in the department (but of course warn them, on discharge, of the possibility of a delayed biphasic recurrence) (Sampson, 2006; Tole, 2007; Kemp, 2008).

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Anaphylaxis, Questions

Posted on November 18, 2011 by

1. How do you define anaphylaxis?  When and how do you give a patient with anaphylaxis epinephrine? How does age or past medical history factor in your decision?

2. When do you consult ENT to scope a patient with an allergic reaction/anaphylaxis?

3. How do you make the decision to intubate a patient with anaphylaxis?

4. Which patients do you admit?  How long do you observe the patients you intend to discharge?

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Sickle Cell Disease, “Answers”

Posted on October 31, 2011 by

 1.)    How do you determine whether or not a sickle cell patient is currently experiencing an acute pain crisis? 

Acute pain crises are one of the most common reasons patients with sickle cell disease (SCD) seek medical attention in the emergency department.  The most common locations SCD patients complain of pain in acute crises are the upper back (63%), left arm (61%), legs (38%), and chest (26%). Episodes can last from 2-7 days (Wilkie, 2010).

The problem, unfortunately, is the widespread belief that exists among  physicians and nurses that opioid addiction and abuse runs rampant within this population.  In a survey of 286 physicians at academic hospitals throughout the US, over 80% of physicians felt that self-reporting was not the most reliable indicator of pain in this patient population (Labbe, 2005).  This often places the emergency physician in a false conundrum: How do I know that my patient is truly experiencing an acute pain crisis versus seeking opioids to feed an addiction?

Some physicians may incorrectly use vital sign abnormalities to attempt to identify the presence of an acute pain crisis; however, no correlation between the two actually exists.  One single-center, retrospective review of 459 SCD patients with acute pain crises found no episodes of hypertension associated with an acute pain crisis (Ernst, 2000).  Another study examining the use of ketoprofen in acute pain crises looked at 66 patient episodes and only found one that included tachycardia (Bartolucci, 2009).

In terms of laboratory data, there is also no correlation with hemoglobin level/reticulocyte count and the presence of an acute pain crisis.  Patients often experience acute pain crises without any drop in their hemoglobin level.  Many large interventional trials among SCD patients report hemoglobin concentrations between 8-10mg/dL in patients experiencing acute pain crises, a level that is similar to the baseline in this patient population (Ballas, 2004 & Bartolucci, 2009).  In fact, there is some evidence to suggest that a lower hemoglobin level portends lower rates of acute pain crises because of lower blood viscosity (Bouchair, 2000).

The bottom line is that there is no combination of clinical or laboratory data that can assist a clinician in determining whether or not a patient is experiencing an acute pain crisis.  Unless there is evidence that a patient does not have SCD, take a patient’s complaint seriously and provide them adequate medication to relieve their pain.

2.)    How do you differentiate an acute pain crisis from pulmonary embolus or acute chest syndrome (ACS)?

In patients with SCD presenting to the emergency department with chest pain, it is important to consider non-SCD-related conditions, such as pulmonary embolus, before attributing pain to SCD.  In SCD patients, the incidence of pulmonary embolism secondary to deep venous thromboembolism (DVT) is similar to non-SCD patients matched by age, sex, and race.  Difficulties arise, however, in diagnosing a PE in patients with SCD as there is often a lack of evidence for DVT and their ventilation-perfusion scans are often abnormal at baseline.  Furthermore, the use of hypertonic intravenous contrast agents commonly used in CT angiography may be unsafe, as it can induce further intravascular sickling and worsen renal insufficiency. Unfortunately, there is little evidence in the literature on how to differentiate between these two diagnoses, beyond that which exists for diagnosing PE in the general population.

It is also vital to consider the diagnosis of acute chest syndrome (ACS) in patients with SCD presenting with acute chest pain, as it is the most frequently reported cause of death in these patients. According to guidelines on sickle cell disease management written by the NIH/National Heart, Lung, and Blood Institute in 2002, the diagnosis is made if a patient with SCD presents with at least two of the following signs/symptoms:

  • Chest pain
  • Fever > 38.5 C (101.3 F)
  • New pulmonary infiltrate on chest x-ray
  • Respiratory symptoms (coughing, wheezing, or shortness of breath)
  • Hypoxemia

Therefore, the evaluation of chest pain in patients with SCD should always include a chest x-ray.  ACS is caused either by infection (especially Chlamydophila pneumonia and Mycoplasma pneumonia), pulmonary infarction from in-situ thrombosis, or fat embolism.  ACS may lead to rapid deterioration in pulmonary status; patients often require ICU-level care.  The cornerstone of treatment resides in administering antibiotics as well as exchange transfusions to increase Hemoglobin A levels to > 70% (NIH/NHLBI, 2002).  

3.)    What do you do for patients once you’ve decided this is an acute pain crisis?  Which lab values are helpful?  Do you provide oxygen and fluids to all your patients in pain crisis? 

Although laboratory data may not assist you in determining whether or not a patient is having an acute pain crisis, they can help you assess the severity of a patient’s disease state as well as identify other emergency states in the sickle cell patient.  As discussed, sickle cell patients maintain a baseline hemoglobin level of approximately 7-10mg/dL and a compensatory reticulocytosis between 5-10%.  An acute drop in their hemoglobin level below their normal baseline may be the first indication of a splenic sequestration crisis (seen in children, primarily), transient red cell aplasia (caused by Parvovirus B19), or hyperhemolytic crisis.  A low reticulocyte count (<1%) may further help pinpoint a transient red cell aplasia, whereas elevated LDH, elevated indirect bilirubin, and decreased haptoglobin levels may be markers for hyperhemolytic crises.

The administration of oxygen to sickle cell patients with acute pain crises is often a reflex we perform upon their arrival in the emergency department.  Some small studies and case reports, however, do demonstrate that giving prolonged supplemental oxygen to non-hypoxic patients with SCD can reduce circulating erythropoietin levels in the body and cause marrow hypoplasia (Embury, 1984 & Lane, 1988).  As a result of these studies, many sickle cell experts recommend providing supplemental oxygen either intermittently or to hypoxic patients only.

In terms of fluids, studies have shown reduced sickling when hypotonic fluids are administered (Clark, 1980). Older evidence also demonstrates an association between excess fluid and atelectasis, a risk factor for acute chest syndrome.  As a result, some clinicians advocate D5 ½ normal saline at a maintenance rate instead of IV fluid boluses of normal saline for all euvolemic patients with sickle cell-related pathologies.

4.)    Which pain medications do you use in patients experiencing an acute pain crisis?

Treatment of pain crises in patients with SCD in the emergency department is primarily accomplished through the use of opiates.  The IV route is preferred due to its predictable pharmacokinetics, but oral and subcutaneous routes may be acceptable if IV access is not available.  Morphine, hydromorphone (dilaudid), and fentanyl are all options for pain control.

The NIH recommends administering opiates by IV push every 15 minutes until a patient’s pain score is reduced by 2 on the “1-10 pain scale” (NIH/NHLBI, 2002). Some studies have shown decreased length of stay in the ED and shorter time to pain relief by using a PCA pump as opposed to bolus doses of opiates (Gonzalez, 1991).  Therefore, if available, consider using a PCA pump even if you suspect the patient will not require admission.

The long-term effects of NSAIDS in patients with SCD are not well-studied.  As some studies show they may be associated with renal injury, especially in children, avoid them.  Similarly, if your department still stocks meperidine, it should be avoided in SCD patients: it is renally cleared, making it unsuitable in a patient population with almost universal renal abnormalities as a result of microvascular infarction (even with normal creatinines).

Both ketamine and magnesium are currently being studied as possible adjunct treatments for patients with acute pain crises.  Low dose ketamine infusions in children may improve pain control and decreased the amount of opioid needed in a pain crisis (Zempsky, 2010).  Magnesium may be associated with a decreased length of stay in patients admitted for acute pain crises.  Further studies are underway to fully evaluate magnesium and ketamine’s incorporation into the management of patients with acute pain crises.   

5.)    Which patients do you admit?  For discharged patients, what is the discharge plan? 

Generally speaking, patients with intractable pain that is not controlled in the emergency department require admission.  The question arises as to what is considered “intractable.”  Some physicians use a cut-off of three IV bolus administrations after which patients are admitted, however no rule can be applied to all patients.  The decision for admission is usually a combined decision between the physician and the patient to evaluate the best method of achieving adequate pain control.

Patients can be discharged home as long as their pain can be controlled by oral medications.  As discussed earlier, pain crises may last between 2-7 days.  Therefore, it is important to inform patients to return to the emergency room if their pain returns to an intolerable level.  Patients should be instructed to avoid situations that may induce pain crises, like cold and dehydration, and to follow-up with their hematologist in the outpatient setting within 2 weeks of discharge.

 

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Sickle Cell Disease, Questions

Posted on October 11, 2011 by

1.)    How do you determine whether or not a sickle cell patient is currently experiencing an acute pain crisis? 

2.)    How do you differentiate an acute pain crisis from pulmonary embolus or acute chest syndrome (ACS)?

3.)    What do you do for patients once you’ve decided this is an acute pain crisis?  What lab values are helpful?  Do you provide oxygen and fluids to all your patients in pain crisis?

4.)    Which pain medications do you use in patients experiencing an acute pain crisis?

5.)    Which patients do you admit?  For discharged patients, what is the discharge plan?

SCD Questions Poster

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