Category Archives: Respiratory

BNP: Data, Diagnosis and Applications

BNP: Data, Diagnosis and Applications

M Lamberta PGY-3

 

What are the Biomarkers?

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ACEP Clinical Policy


Natriuretic Peptide (NP) assays gained approval by the FDA around the year 2000 for the evaluation of undifferentiated dyspnea and suspected ADHF.  The first commercially available test detected the biologically active hormone BNP, but many more recent assays also detect the inert Amino-terminal cleavage product of the BNP prohormone: N-Terminal proBNP (NT-proBNP). (Table 1)  Both biomarkers are comparable in their diagnostic accuracy demonstrated by Receiver Operating Characteristic (ROC) curves. 

 

From 1999 to 2000, Maisel et al. recruited 1,586 participants in the first large multinational randomized control trial (RCT) to evaluate BNP for the diagnosis of heart failure in ED patients presenting with acute dyspnea.[1].  The Breathing Not Properly (BNP) study analyzed a subgroup from this cohort to conclude that adding BNP to clinical judgment would have enhanced diagnostic accuracy from 74% to 81%.  This trial supported BNP as a good rule-out test for Acute Decompensated Heart Failure (ADHF) with a sensitivity of 90% for BNP < 100 pg/mL when compared to the gold standard: blinded assessment of two independent cardiologists.   The authors also argued that BNP ruled-in 14 of the 19 patients that were erroneously diagnosed by clinicians as “CHF improbable,” thereby reducing false negatives from 2% to 0.6%.  The improved sensitivity, however, inevitably reduced specificity to near 74% for a cut-off of BNP ≥100 pg/mL. [2] Furthermore, a secondary analysis pointed out the limited application of this biomarker as clinical judgment seemed to outperform BNP assay when applied to the dyspneic patient at the extremes of pretest probability ie greater than 95% or less than 5% certainty of ADHF. [3] Therefore, a higher rule-in threshold (BNP > 500 pg/mL improved specificity of this assay but also opened up a “gray-zone” in the interpretation of BNP where the test could neither rule-in nor rule-out with good certainty.  

By the mid-2000s, the rule-out and rule-in cut-offs for CHF began to gain modest support by professional organizations including ACEP. [4]  Wang et al. contributed to JAMA’s Rational Clinical Examination series by conducting a meta-analysis of these preceding data in addition to 20 smaller studies on BNP to determine Likelihood ratios for BNP.  The meta-analysis calculated a negative likelihood ratio (LR-) near 0.9 (cut-off <100 pg/mL) again promoting BNP as a strong test to rule-out ADHF.  Yet, comparing BNP to patient history “significant for heart failure” (LR+ 5.8) or  “interstitial edema” on chest X-Ray (LR+ 12), BNP stood as an equivocal test to rule-in HF with LR+ 2.7 (≥100 pg/mL).[5]

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In the later 2000s, large RCTs would similarly establish the accuracy of NT-proBNP in ADHF.  The PRIDE (N-Terminal Pro-BNP Investigation of Dyspnea in the Emergency Department) constructed ROC curves to conclude that adding NT-proBNP to the evaluation of patients with dyspnea was superior to clinician-estimated likelihood of CHF alone with area under the curve (AUC) measuring 0.90 for clinician alone versus 0.94 for clinician+NT-proBNP, (p = 0.006).[6]  The Canadian IMPROVE-CHF study affirmed similarly that adding NT-proBNP to clinical judgment alone increased the AUC from 0.83 to 0.90. [7]

Despite showing statistical differences in diagnostic accuracy through Receiver-Operator Characteristic Curves, the application of natriuretic peptides did not appear to add much to clinical judgement at the extremes of pre-test probability, so many began to apply it to patients who were considered intermediate pretest probability  (21% to 79%) or under circumstances of competing diagnoses ie COPD vs PNA vs CHF.  Steinhart et al. attempted to better stratify these “intermediate probability” patients by deriving an algebraic model that capitalized on increased positive likelihood ratios at higher absolute levels of NT-proBNP.  In a validation study, this model appeared to correctly reclassify 44% of the “intermediate” patients to either low risk or high risk.  The strength of this approach is that it provides for practical application of NT-proBNP as a continuous variable rather than just relying on discrete cut-offs, it accounts for age-adjusted variability, and it prompts the clinician to appropriately consider pre-test probability before interpreting the test result.  The weakness lies in the fact that it requires math (yet, an excel model is available for download here), and it does not appear to approve diagnostic accuracy in a majority of cases.  In this study, the model helped to correctly reclassify 10% of the study participants. [8,9]

When NPs came to the scene 15 years ago the hope was that it would be the “super-hero” for the bewildered clinician in the diagnosis of dyspnea, but subsequent trials and meta-analyses gave BNP the persona of  more of a “yes-man” supporting what the clinician already knew and equivocating just as much for cases of “intermediate probability.”    The literature of the last 15 years has elucidated NP test characteristics, confounding variables (Tables 1 and 2), and interpretation, but application of the test still appears rather heterogeneous by anecdote as either a rule-in, rule-out, adjudicator, or prognosticator.   

 

Discussion:

  • Ruling-in low-probability:  BNP as a rule-in test to diagnose patients who are being treated erroneously for other conditions ie a 65-year-old patient with a history of COPD but no current diagnosis of HF. Rosen even suggests “we abandon the routine obtaining of a BNP level for patients deemed to be having a CHF flare-up, and instead consider it in all dyspnea patients that we don’t believe are having CHF.” [10] This implies a sentiment of screening.  In an older population, where prevalence is higher, it may be a good consideration.
  • Ruling-out high-probability:  As expenditures for heart failure continue to soar, the use of BNP, in concert with other clinical signs and adjunct studies, may have significant application for ruling-out ADHF in known HF patients. This may lead to scoring protocol or institutional decision rules to help identify ED patients who are safe for outpatient management.
  • Adjudicating intermediate risk:  Likely BNP will continue to find application case-by-case by the ED clinician who is interested in detecting the presence of heart strain whether it will change management or not.  Interpretation of BNP should be considered after establishing pre-test probability for the patient, with the knowledge of confounding variables, and can employ tools to interpret the test like that proposed by Steinhart et al. (available for download here).  That said, the same cases of intermediate probability will more likely represent the complex and sicker patients requiring longer hospital stays and extended work-ups and more than half the time the knowledge of BNP will unlikely help to narrow the diagnosis. [9]
  • Prognosticating: Elevated BNP almost always suggests a poor prognosis whether it is used to stratify ADHF, NSTEMI, or PE, but prognosis is often more accurately reflected—and more easily assessed—by patient hemodynamics and renal perfusion. [11,12,13] There is no strong evidence that BNP will consistently help an admitting team in their management, but there is still ongoing research discerning how BNP may help in response-guided therapy and discharge planning.
  • Outcomes: Only a handful of randomized controlled trials have measured changes in outcomes for clinicians who use natriuretic peptide assays in the ED.  Meta-analyses of these trials have shows trends towards decreased cost and length of stay, but no reproducible significant difference in these outcomes or in regards to therapy or mortality.  [14,15]

 

 

Citations

  1. Maisel AS, Krishnaswamy P, Nowak RM, et al. Rapid measurement of B-type natriuretic peptide in the emergency diagnosis of heart failure. N Engl J Med. 2002;347:161-167.
  2. McCullough PA, Nowak RM, McCord J, et al. B-type natriuretic peptide and clinical judgment in emergency diagnosis of heart failure: analysis from Breathing Not Properly (BNP) Multinational Study. Circulation 2002;106:416–22
  3. Schwam E. B-type natriuretic peptide for diagnosis of heart failure in emergency department patients: a critical appraisal. Acad Emerg Med. 2004;11:(6)686-91.
  4. Silvers SM, Howell JM, Kosowsky JM, Rokos IC, Jagoda AS. Clinical policy: critical issues in the evaluation and management of adult patients presenting to the emergency department with acute heart failure syndromes. Ann Emerg Med 2007;49:627–69. (BNP Clinical Policy)  http://www.acep.org/workarea/DownloadAsset.aspx?id=8778
  5. Wang CS, FitzGerald JM, Schulzer M, Mak E, Ayas NT. Does this dyspneic patient in the emergency department have congestive heart failure? JAMA 2005;294:1944–56
  6. Januzzi JL Jr, Camargo CA, Anwaruddin S, et al. The N-terminal Pro-BNP Investigation of Dyspnea in the Emergency Department (PRIDE) study. Am J Cardiol. 2005;95:948-954.
  7. Moe GW, Howlett J, Januzzi JL, Zowall H, for the Canadian Multicenter Improved Management of Patients With Congestive Heart Failure (IMPROVE-CHF) Study Investigators. N-terminal pro-B-type natriuretic peptide testing improves the management of patients with suspected acute heart failure: primary results of the Canadian prospective randomized multicenter IMPROVE-CHF study. Circulation 2007;115:3103–10
  8. Emergency Medicine Journal Club. Does BNP Augment Acue Decompensated CHF ED Management. WUSM-St. Louis. Journal Club November, 2009. http://emed.wustl.edu/education/EmergencyMedicineJournalClub/Archive/November2009.aspx
  9. Steinhart B, Thorpe KE, Bayoumi AM, Moe G, Januzzi JL, Mazer CD. Improving the diagnosis of acute heart failure using a validated prediction model. J Am Coll Cardiol 2009;54:1515–21.
  10. Carpenter CR, Keim SM, Worster A, Rosen P, BEEM (Best Evidence in Emergency Medicine). BRAIN NATRIURETIC PEPTIDE IN THE EVALUATION OF EMERGENCY DEPARTMENT DYSPNEA: IS THERE A ROLE? The Journal of Emergency Medicine. 2012;42(2):197-205.
  11. Heeschen C, Hamm CW, Mitrovic V, et al. N-terminal pro-B-type natriuretic peptide levels for dynamic risk stratification of patients with acute coronary syndromes. Circulation. 2004 Nov 16. 110(20):3206-12.
  12. Binder L, Pieske B, Olschewski M, et al. N-terminal pro-brain natriuretic peptide or troponin testing followed by echocardiography for risk stratification of acute pulmonary embolism. Circulation. 2005 Sep 13.
  13. Singer AJ, Birkhahn RH, Guss D, et al. Rapid Emergency Department Heart Failure Outpatients Trial (REDHOT II): a randomized controlled trial of the effect of serial B-type natriuretic peptide testing on patient management. Circ Heart Fail 2009;2:287–93.
  14. Trinquart L, Ray P, Riou B, Teixeira A. Natriuretic peptide testing in EDs for managing acute dyspnea: a meta-analysis. Am J Emerg Med. 2011;29:(7)757-67
  15. Lam LL, Cameron PA, Schneider HG, et al. Meta-analysis: effect of B-type natriuretic peptide testing on clinical outcomes in patients with acute dyspnea in the emergency setting. Ann Intern Med 2010; 153: 728−735.

 

Figures

LB Daniels, AS Maisel. Natriuretic Peptides. J Am Coll Cardiol. 2007 Dec 18. 50(25): 2357-68. (Tables 1-2)

 

Continued Reading

JM Kosowsky, JL Chan. Acutely Decompensated Heart Failure: Diagnostic and Therapeutic Strategies. EB Medicine Review (2006). https://www.ebmedicine.net/topics.php?paction=showTopic&topic_id=87

Mueller TT. Head-to-head comparison of the diagnostic utility of BNP and NT-proBNP in symptomatic and asymptomatic structural heart disease.. Clinica chimica acta. 2004-03;341:41-48.

 

SEATTLE II

Stephanie Haimowitz, PGY3

 

AS is a 43 yo F, on OCPs for menorrhagia, h/o recent left ACL tear and as a result decreased ambulation x3 weeks, p/w SOB, worse on exertion x2 weeks but acutely worsening on the day of presentation. On the day of presentation, the patient complained of an episode of acutely worsening dyspnea, now occurring at rest and associated with lightheadedness, chest pressure, and diaphoresis.

On Exam, the patient was mildly tachycardic with an O2 sat of 98% on RA at rest. She appeared to be breathing comfortably, although at times noted to take shallow breaths, and the remainder of her exam was unremarkable.

Labs were notable for an elevated troponin of 0.302. EKG showed sinus tach with a ventricular rate of 106 and an incomplete RBBB. CT w/PE protocol showed large bilateral pulmonary emboli in both the right and left main pulmonary arteries with extension into segmental and subsegmental branches, as well as flattening of the interventricular septum with dilatation of the right ventricle.

BL-PE

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The patient was started on a heparin drip and admitted to the CCU for hemodynamic monitoring and catheter directed thrombolysis via EKOS, which uses ultrasound to enhance the effects of catheter directed thrombolysis. The patient underwent the endovascular intervention with improvement in her symptoms and repeat echo showed improved RV function. She was switched to Lovenox and discharged home on xarelto.

There are many factors to consider when choosing the appropriate treatment modality for a patient with a PE. In a well-appearing hemodynamically stable patient with evidence of a peripheral or subsegmental PE, anticoagulation with either heparin, a low molecular weight heparin such as lovenox, or one of the newer factor Xa inhibitor oral agents is the most common treatment modality. Factors to consider when deciding whether to escalate treatment include hemodynamic instability, evidence of right heart strain, a large central thrombus on CT, and overall clinical appearance.

While this patient was hemodynamically stable, she had clear evidence of right heart strain (e.g. troponemia, dilated right ventricle, flattening of interventricular septum, and McConnell’s sign- diminished RV systolic function with sparing of the apical wall seen here), and large bilateral pulmonary emboli on CT scan. The RV dysfunction seen on echo is often considered to be predictive of a poor short-term prognosis, thus warranting more aggressive therapeutic measures.[1]

The decision was made to use ultrasound enhanced catheter directed fibrinolysis.

The SEATTLE II Study, published in August of this year, investigated the efficacy of this technique. The use of full dose systemic thrombolysis has fallen out of favor over the past few years due to the risks of severe bleeding and intracranial hemorrhage. By using the ultrasound guided catheter directed approach, a lower dose of thrombolytic can be used because it is injected adjacent to the PE. The study was a single-arm, multicenter design with the inclusion criteria of a proximal PE, age >18, PE symptom duration <14 days, and RV/LV diameter ratio >0.9 on CT. A total of 150 patients were enrolled at 22 sites across the US, at urban, non-urban, teaching, and non-teaching hospitals. The primary outcome was a change in RV/LV diameter ratio pre and post procedure. The primary safety outcome was major bleeding within 72 hours of initiation of therapy. Major bleeding was defined as either intracranial hemorrhage or bleeding causing hemodynamic compromise and requiring intervention such as blood transfusion. Patients enrolled in the study had a mean difference RV/LV diameter of 0.42. There were 16 major bleeding events, however none of these were intracranial hemorrhage.[2]

The most glaring limitation of the study was the lack of a comparator group, such as full dose systemic fibrinolysis, half dose systemic fibrinolysis, or a/c alone. Thus, while the results of the study appear promising, additional comparative clinical studies are necessary to help define the role of ultrasound facilitated catheter directed fibrinolysis in the treatment of acute PE.

 

—-

References:

[1] 14.Grifoni S, Olivotto I, Cecchini P, et al. Short-term clinical outcome of patients with acute pulmonary embolism, normal blood pressure, and echocardiographic right ventricular dysfunction. Circulation 2000; 101:2817.

[2] Piazza, Gregory, Benjamin Hohlfelder, Michael R. Jaff, Kenneth Ouriel, Tod C. Engelhardt, Keith M. Sterling, Noah J. Jones, John C. Gurley, Rohit Bhatheja, Robert J. Kennedy, Nilesh Goswami, Kannan Natarajan, John Rundback, Immad R. Sadiq, Stephen K. Liu, Narinder Bhalla, M. Laiq Raja, Barry S. Weinstock, Jacob Cynamon, Fakhir F. Elmasri, Mark J. Garcia, Mark Kumar, Juan Ayerdi, Peter Soukas, William Kuo, Ping-Yu Liu, and Samuel Z. Goldhaber. “A Prospective, Single-Arm, Multicenter Trial of Ultrasound-Facilitated, Catheter-Directed, Low-Dose Fibrinolysis for Acute Massive and Submassive Pulmonary Embolism.”JACC: Cardiovascular Interventions 8.10 (2015): 1382-392. Web.

A Discussion of the Effects of Succinylcholine on Intracranial Pressure in Patients with Acute Brain Injury Requiring Rapid Sequence Intubation with or without Pretreatment with a Neuromuscular Blocking Agent- Dr. Alexander Le

BullwinkleCheeriosMuscle

Acute brain injuries (whether due to traumatic brain injury (TBI), spontaneous hemorrhage, or other cause) are a significant public health concern and major cause of morbidity and mortality worldwide. Patients with acute brain injuries frequently require mechanical ventilation, and emergent control of the airway is a time-sensitive, paramount step in management. Rapid sequence intubation (RSI) offers timely control of the airway while maintaining oxygenation and minimizing the risks of aspiration and hypercapnea. Of the choices of paralyzing agents used for RSI, succinylcholine (SCH) is widely favored due to its rapid onset and offset and consistency in achieving excellent intubating conditions.(10) In cases of acute brain injury, the use of SCH has been controversial as it has been implicated as a potential cause of increased intracranial pressure (ICP). This paper will briefly review the human evidence relating SCH to ICP, as well as the possibly mitigating practice of pretreating with a neuromuscular blocking agent prior to SCH.

A study by Minton et al is frequently cited as evidence that SCH increases ICP and a competitive neuromuscular blocker should be administered beforehand.(9) This study involved 19 patients with brain tumors undergoing elective surgery. The patients were intubated, mechanically ventilated, and anesthetized with thiopental before being given SCH alone and then SCH following a dose of vecuronium. Increases in ICP were observed with administration of SCH alone, but not when preceded by vecuronium. (The average ICP increased 4.9+2 mmHg) Of note, vecuronium was given at a full paralyzing dose (0.14 mg/kg), not the lower defasciculating dose. While this study suggests a significant rise in ICP secondary to SCH administration which is mitigated by pretreatment, it contained a small number of patients who served as their own controls and did not have acute brain injuries or undergo RSI. Furthermore, it used vecuronium at a full paralyzing dose rather than a defasciculating dose.

Another commonly cited study by Stirt et al involved 12 patients undergoing surgery for brain tumors.(11) The group of 6 patients who received SCH without pretreatment experienced increased ICPs ( Average about 10mm HG) compared to the 6 who were pretreated with metocurine 7 minutes prior to being given SCH. While this study supports pretreatment prior to SCH administration, it is small and the patients did not have acute brain injuries or undergo RSI.

A study by Marsh et al found a small, but significant increase in ICP with SCH in 8 patients having elective surgery for brain tumors.(7)

The following studies offer opposing evidence that SCH does not have a significant effect on ICP. Kovarik et al studied 10 mechanically ventilated patients with TBI in an ICU setting who were given SCH at a dose of 1 mg/kg compared to a small volume of normal saline. They did not find any significant change in ICP, mean arterial pressure, or cerebral perfusion pressure.(5)

Brown et al performed a randomized, double blind trial of 11 patients with severe TBI. The patients were intubated, mechanically ventilated, sedated and received either SCH (1 mg/kg) or normal saline of an equal volume. No significant changes in ICP or CPP were detected.(3)

White et al studied the effects of several drugs on blunting the response of ICP to endotrachial suctioning in 15 comatose ICU patients with diffuse brain injury. There was no significant change from baseline ICP after the administration of SCH and endotrachial suctioning over a fifteen minute time period.(12)

A study by Barrington et al found that administration of SCH with atropine prior to intubation prevented an increase in ICP that was found with atropine alone in 20 preterm infants, and was associated with shorter intubation times.(1)

Lam et al measured lumbar CSF pressure in 24 patients undergoing elective aneurysm clipping and did not find any significant increase in ICP after SCH administration.(6)

McLesky et al similarly looked at 4 patients undergoing elective neurosurgery for brain tumors and found no significant increase in ICP with SCH.(8)

There are unfortunately no large, randomized control trials to answer the question of the effects of SCH on ICP. The available human evidence is comprised of small studies, which demonstrate conflicting results. Similarly, there is not sufficient evidence to support the routine use of pretreatment with a neuromuscular blocking agent to blunt a possible (and questionable) increase in ICP secondary to SCH.(2,4) While the limited evidence for use of a neuromuscular blocking agent as pretreatment suggests some benefit, it should only be considered if it does not delay the establishment of a definitive airway when it is required.

References:
1. Barrington KJ, Finer NN, et al. Succinylcholine and atropine for premedication of the newborn infant before nasotracheal intubation: a randomized, controlled trial. Crit Care Med 1989;17:1293–6.
2. BET 3: Suxamethonium (succinylcholine) for RSI and intubation in head injury
Emerg Med J 2012;29:6 511-514 doi:10.1136/emermed-2012-201374.4
3. Brown MM, Parr MJA, et al. The effect of suxamethonium on intracranial pressure and cerebral perfusion pressure in patients with severe head injuries following blunt trauma. Eur J Anaesthesiology 1996;13:474–7.
4. Clancy M, Halford S, Walls R, et al. In patients with head injuries who undergo rapid sequence intubation using succinylcholine, does pretreatment with a competitive neuromuscular blocking agent improve outcome? A literature review. Emerg Med J, 18 (2001), pp. 373–375
5. Kovarik WD, Mayberg TS, et al. Succinylcholine does not change intracranial pressure, cerebral blood flow velocity, or the electroencephalogram in patients with neurologic injury. Anesth Analg 1994;78:p469–73.
6. Lam AM , Nicolas JF, Manninen PH. Influence of succinylcholine on lumbar cerebral spinal pressure in man. Anesth Analg1984;63:240
7. Marsh ML, Dunlop BJ, Shapiro HM, et al. Succinylcholine-intracranial pressure effects in neurosurgical patients. Anesth Analg1980;59:550
8. McLeskey CH, Cullen GF, et al. Control of cerebral perfusion pressure during induction of anesthesia in high-risk neurosurgical patients. Surv Anesthesiology 1976;20:30.
9. Minton MD, Grosslight K, et al. Increases in intracranial pressure from succinylcholine: prevention by prior nondepolarizing blockade. Anesthesiology 1986;65:165–9.
10. Perry J, Lee J, Wells G. Rocuronium versus succinylcholine for rapid sequence induction intubation. Cochrane Database Syst Rev 2003;1:CD002788.
11. Stirt JA, Grosslight KR, et al. Defasciculation with metocurine prevents succinylcholine-induced increases in intracranial pressure. Anesthesiology 1987;67:50–3.
12. White PF, Schlobohm RM, et al. A randomized study of drugs for preventing increases in intracranial pressure during endotracheal suctioning. Anesthesiology 1982;57:242–4.

Why We Do What We Do: Limitations of the PERC Score in PE – Dr. Jason West

When the PERC Rule Fails      

  Kline et al (1) developed a clinical decision tool based on parameters that could be obtained from a brief initial assessment to reasonably exclude the diagnosis of pulmonary embolism (PE) without the use of D-dimer in order to prevent unnecessary cost and the use of medical resources.  Even our interns have used the PERC rule by now, but we should be clear on what it includes: The PERC rule includes age < 50, HR < 100, oxygen saturation on RA > 94%, no prior history of DVT or PE, no recent trauma or surgery, no hemoptysis, no exogenous estrogen, and no clinical signs suggestive of DVT. 

 A review and meta-analysis published in the Annals in 2012 (2) found 12 qualifying studies evaluating the PERC rule and ultimately determined that the pooled sensitivity to rule out pulmonary embolism is 97.2%, which the authors concluded to be a low, but acceptable sensitivity to rule out PE without further testing.  The overall proportion of missed PEs was 0.32% (44 of 13,855 total cases).

 So who are the CT-PE or V/Q positive patients who could have been falsely “PERC ruled out?”

 In other words…when does the PERC rule fail?

 Kline reworked the data from a previous paper showing the outcomes of patients who presented to the ED and were diagnosed with PE (3), and used it as a dataset to determine the characteristics of patient who received an ED diagnosis of PE, but could have been included in the PERC clinical decision tool.  The initial study was used to determine that the overall morality attributed to PE was 1%, the mortality from hemorrhage was 0.2%, and the all cause 30 day mortality was 5.4%.  In the reworking of this dataset of 1,880 patients, Kline et al (4) found that 114 would have been included in the PERC rule should it have been applied. 

 Of these patients, they found that only 3 variables that demonstrated a true difference in the proportions between those who would have been included within the PERC rule and those who would have not been able to be “PERC ruled out:” pleuritic chest pain, pregnancy, and postpartum status.  Specifically, pleuritic chest pain, which is not included in any clinical decision rule to risk stratify potential PE patients, was found in 56% of the patients where the PERC rule would have failed. Although the N numbers were small for pregnancy and postpartum status, they concluded that the PERC rule should not be used in isolation to rule out PE in patients who are either pregnant or postpartum.  Again, it should be noted that pleuritic chest pain is not a component of either the Wells PE or revised Geneva score for PE. 

 And the reason for its absence in these scores could be considered questionable.  A large study including nearly 8,000 patients of whom 7.2% had PE by Courtney et al published in the Annals in 2010 (5) was designed to study the variables commonly believed to modify the pretest probability of PE and those already within the existing pretest probability scores.  The odd ratio (OR) for pleuritic chest pain in patients diagnosed with PE was 1.53, which seems weak in comparison to the ORs for history of PE and unilateral leg swelling, which are 2.9 and 2.6, respectively.  However, the ORs for hemoptysis and tachycardia (defined in this study as a pulse of > 94) are 0.78 and 1.52.  Both of these factors are included in the Wells PE score and the revised Geneva score.  Excluding hemoptysis and tachycardia, however, all variables used in the Well PE score have higher ORs than pleuritic chest pain.  The next closest OR of the variables included in the Wells PE score is immobilization with an OR of 1.72.  The authors also found that the other two variables not included in clinical decision rules with useful ORs were a personal history of non-cancer related thrombophilia (OR 1.99) and a family history of PE (OR 1.51).

 It is important to note that the PERC rule was never intended to be applied to anything but a low risk group of patients determined either by clinical gestalt or by the Wells PE score, and this point has been stressed in commentary (6). Only after knowing and applying the Wells PE score, an alternative method of risk stratification, or your clinical gestalt should you consider the PERC Rule in a patient you believe is at low risk for PE.  As our Monte Chairmen, Dr. Gallagher, has pointed out several times, if we believe that our patient population in the “Bx boro” has a higher prevalence of both DVT and PE than the general population in which these rules were derived, then our use of these decision rules, however well-validated in the literature, should be employed with some hesitance.  In fact, the meta-analysis found some heterogeneity in the PERC rule sensitivity to exclude PE.   Two studies from European populations with a prevalence of PE ranging from 21-30% (7,8) found that a negative PERC rule combined with the low risk Revised Geneva Score only reduced the prevalence of PE in the studied patients to 6%.  Only in one of these studies (7), did the PERC rule combined with clinical gestalt reduce the prevalence of PE down to nearly zero.

 Take home points:

  •  The PERC rule cannot be a substitute for gestalt.
  •  Gestalt or some form of risk stratification should be employed first before using the PERC rule.
  • The only evidence we have about PERC rule inclusive CT-PE or V/Q positive patients suggests that 56% of those will have pleuritic chest pain, which is not in a validated clinical decision rule despite having a higher OR for PE than hemoptysis and recent immobilization.
  •  The PERC rule should not be used in isolation to rule out PE in pregnant or postpartum patients.

  Jason West MD

 References:

 1). Kline JA, Mitchell AM, Kabrhel C, et al. Clinical criteria to prevent unnecessary diagnostic testing in emergency department patients with suspected pulmonary embolism. J Thromb Haemost. 2004;2:1247-1255.

 2). Singh, et al. Diagnostic Accuracy of Pulmonary Embolism Rule-Out Criteria: A Systematic Review and Meta-analysis. Ann Emerg Med. 2012;59:517-520.3).

 3). Pollack CV, et al. Clinical Characteristics, Management, and Outcomes of Patients Diagnosed With Acute Pulmonary Embolism in the Emergency Department Initial Report of EMPEROR (Multicenter Emergency Medicine Pulmonary Embolism in the Real World Registry). J Am Coll Cardiol. 2011 Feb 8;57(6):700-6

 4). Kline JA, et al. Clinical Features of Patients With Pulmonary Embolism and a Negative PERC Rule Result. Ann Emerg Med. 2013 January 60(1): 122-124.

 5). Courtney DM, et al. Clinical features from the history and physical examination that predict the presence or absence of pulmonary embolism in symptomatic emergency department patients: results of a prospective, multi-center study. Ann Emerg Med. 2010 April 55(4): 307–315.

 

Why We Do What We Do: Cuffed Tubes versus Uncuffed Tubes in Pediatrics

In choosing the tube size, one must consider choosing between cuffed and uncuffed tubes. For many years, uncuffed tubes have been recommended for children under 8 yrs of age. The uncuffed tube is to be positioned to form a seal at the cricoid ring; the narrowest portion of the child’s airway. However, a great debate has developed in the world of anesthesia when choosing between a cuffed tube and uncuffed tube. Those who are against cuffed tubes note the paucity of randomized control trials justifying their use. In a pro-con paper discussing the issue, Weber (2009) noted the internal diameter of the cuffed tube will inevitably be smaller due to its thicker wall coupled by the diameter that the cuff adds to create the seal within the trachea. Further, the variability of size from different manufactures may cause for overestimation in size and subsequent subglottic stenosis. Following intubation in the ED, prehospital setting and ICU, intracuff pressure is something that can be variable and frequently overlooked. Inadvertent high pressures due to overinflation may cause for tissue ischemia (Ho et al., 2002). In the pediatric populations, it is recommended to maintain cuffs at a high volume and a low pressure around 25 mmHg (Leong & Black, 2009). Ho et al also described variability when describing the margin of safety in pediatric intubations looking at two different types of cuffed tubes. The margin of safety is defined as the distance from the vocal cords to the point of the carina where the tube is to be positioned. Using cuffed pediatric tubes, the researchers noted a 50% reduction in that margin of safety with cuffed tubes compared to uncuffed tubes. These results were more pronounced at younger ages. The study suggests that this may result in “obstruction of upper lobe bronchi” and possible suboptimal position with migration of the tube with any significant neck movement.

Advocates of the cuffed tubes combat these arguments sighting a number of papers associated with advantages and clinical experience. Khine et al (1997) in his landmark study, was the first to note no difference in the incidence of post-intubation stridor between cuffed and uncuffed intubated patients. He also noted the incidence of reintubation due to air leak was reduced in the cuffed cohort (5.5%) compared to the uncuffed cohort (17%). Murat (2001) responding to an editorial on cuffed endotracheal tubes (James 2001), reported that 15000 pediatric patients (including 904 under the age of 1) had been intubated at his institution using cuffed tubes. Of those 15000, there were no reports of subglottic stenosis or respiratory complications associated with the type of tube used. Echoing these findings from the operating room, Meyer et al (2000) and Newth et al (2004) both reported on experience in both the emergency department and PICU respectively and found no significant complications associated with cuffed endotracheal tubes. James (2001) noted that a reduction of airleak as an important quality ascribed to cuffed endotracheal tubes. A sealed system allows for consistency in administration of tidal volumes and positive end expiratory pressure as well as provides for better measurement of lung compliance and airway resistance. Eschertzhuber et al (2010) noted that cuffed tubes reduce the amount of leaked anesthetic gases in the operating room. This gas leak has both environmental pollution implications as well as financial implications as anesthetics are being wasted. Another added advantage of the cuff is a reduction in gastric contents being aspirated. Gopalareddy et al (2007) demonstrated a reduction in tracheal aspirates containing gastric pepsin found in patients with cuffed tubes (53%) vs uncuffed (100%). The study, however, did not demonstrate an increase in chest xray findings associated with increased tracheal aspiration.

Although the debate regarding cuffed vs uncuffed is still up in the air, most literature seems to suggest that the use of a cuffed tube in pediatric patients above 1 year of age can use is not inferior to the use of uncuffed tubes and may actually have some advantage. Ultimately it is the provider’s comfort with the various tools that will navigate his or her practice.

Reference:

Bae et al., Usefulness of ultrasound for selecting a correctly sized uncuffed tracheal tube for paediatric patients, Anaesthesia, 2011; 66:994-98.

Eschertzhuber et al., Cuffed endotracheal tubes in children reduce sevoflurane and medical gas consumption and related costs. Acta Anesthesiol Scand 2010; 54:855-58.

Gopalareddy et al., Assessment of the prevalence of microaspiration by gastric pepsin in the airway of ventilated children, Acta Paediatrica 2008; 97:55-60.

Ho et al., The Margin of safety associated with the use of cuffed paediatric tracheal tubes, Anaesthesia, 2002; 57:169-82.

Hofer et al., How reliable is length-based determination of body weight and tracheal tube size in the paediatric age group? The Broselow tape reconsidered, Br J Anaesth 2002; 88:283-5.

James, I, Editorial: Cuffed Tubes in Children, Paediatric Anaesthesia 2001; 11:259-263.

Khine et al., Comparison of cuffed and Uncuffed Endotracheal Tubes in Young Children during General Anesthesia, Anesthesiology 1997; 86:627-13

Leong L & Black AE, The design of pediatric tracheal tubes, Ped Anesthesia 2009; 19(Suppl. 1):38-45.

Meyer et al., Comlpications of emergency tracheal intubation in severely head-injured children. Ped Anaesthesia 2000; 10:253-260.

Murat, I, Cuffed tubes in children: a 3-year experience in a single institution. Ped Anaesthesia 2001; 11:745-750.
Newth et al., The use of cuffed versus uncuffed endotracheal tubes in pediatric intensive care, J Pediatr 2004; 144:333-7.

Weber, T et al., Pro-Con Debate: Cuffed vs non-cuffed endotracheal tubes for pediatric anesthesia, Ped Anesthesia 2009; 19*Suppl. 1): 46-54.

Why We Do What We Do: HELIOX

A young child comes to the ED with diffuse wheezing and retractions. You diagnose the patient with RSV bronchiolitis. The child’s oxygen saturation is in the low 90’s and is working very hard to breath. You have tried albuterol but the patient’s symptoms aren’t getting much better. You are concerned you might have intubate this patient if you do not find another solution quickly. Check out the article attached and the thoughts below to offer a possible solution.

Noninvasive ventilation with helium-oxygen in children – J of Critical Care 2012

HELIOX is a combination of both Oxygen and Helium. Helium being an inert gas with a low molecular weight has a low density (7x less density). Nitrogen on the other hand has a higher molecular weight and higher density. By replacing nitrogen with helium we are effectively decreasing the amount of work it takes to move air as we have reduced the resistance to flow. Further HELIOX allows for better CO2 diffusion at a rate “4-5 times faster than in air-oxygen mixture”.

HELIOX has been shown to be very effective in treating COPD in the adult literature. The article suggests that it is also effective in the pediatric populations, especially in obstructive pathology including: croup, bronchiolitis, status asthmaticus, angioedema, post extubation subglottic edema, etc. It is recommended that a nonrebreather mask be used at flows of 10-15mL/min. Nebulizing medicines at 10-12mL/min using Heliox is also an effective technique for delivery. In combination with NIV (noninvasive ventilation) Heliox may obviate the need for intubation. Due to its low density and ease of flow, “HELIOX can decrease the pressure gradient required to maintain a given flow, less pressure can be used to obtain the target tidal volumes, which, in turn, diminishes peak pressures and minimizes the risk of barotrauma and volutrauma.”

So why aren’t we using this gas on everybody? It does have some pitfalls. There is some anecdotal evidence that it may cause hypoxia secondary to atelectasis. The authors suggest we use CPAP to address this issue as it will stent the aveoli open. Due its thermal conductive properties, prolonged HELIOX administration at 36 degrees celcius may cause for hypothermia in neonates and small infants. So try to warm the gas if you can. HELIOX is also relatively expensive when compared to other therapeautic gases (oxygen) and requires special modifications to ventilator devices to accommodate its use.

That being said….if you have HELIOX available and a nonrebreather or nebulizer it may be a solution that prevents you from having to intubate a child who is not looking like a peach.

Reference:
Martinon-Torres MD, Phd, F “Noninvasive ventilation with helium-oxygen in children” J of Critical Care (2012) 27, 220e1-220e9.