An evidence-based emergency medicine podcast. The Washington University Emergency Medicine Journal Club podcast provides an excellent way to keep up with the medical literature, improve patient care, and increase understanding of evidence-based medicine. Each month we ask a clinical or operational question pertinent to the practice of emergency medicine. We then discuss the four articles most relevant to that question in an attempt to determine the most evidence-based approach to patient care.
It's two o'clock in the afternoon during a typical weekend TCC shift, when you get a page that a triage patient is coming to room 4. You look at the chart and see that it's a 45-year-old man who was riding his horse and got bucked off, landing on his left arm in an awkward position. The triage nurse has noted a deformity to the upper arm with intact pulses and sensation distally. You notice that the triage doctor has ordered IV lidocaine for the man, which you find most confusing.
Your evaluation of the patient confirms much of the triage note. He has swelling and bruising to the left upper arm, concerning for a mid-shaft humerus fracture. He is neurovascularly intact and has stable vital signs. He denies any past medical history and has no allergies.
You decide to ask your attending about the IV lidocaine, which the patient says hasn't really helped his pain, but Dr. Cohn just shakes his head and sighs. You then ask about giving the patient low-dose ketamine for his pain, having recently listened to a podcast on the subject (SGEM#130: Low Dose Ketamine for Acute Pain Control in the Emergency Department). Dr. Cohn laughs in your face and turns his back on you. Later, he comes back and explains that while he admittedly hasn't read the literature on the subject, he isn't a big fan of replacing one addictive substance with another, especially one that's less familiar to him.
Curious about what the evidence actually shows, and wanting to be prepared to look smart in front of your pompous attending, you decide to search the literature and see what the evidence actually shows...
PICO Question:
Population: Adult patients in the ED with acute pain
Intervention: IV ketamine
Comparison: Usual care with IV opiate analgesia
Outcome: Pain control, adverse events (hypoxia, respiratory depression, dysphoria, etc.), patient satisfaction, ED length of stay
Search Strategy:
PubMed was searched using the terms “ketamine AND analgesia AND emergency”, resulting in 169 articles (http://tinyurl.com/znjvzc4). The titles of these were searched, and the four most relevant articles chosen.
The literature on this topic is still somewhat limited, primarily comprising small studies that compare morphine to ketamine alone, or to combination therapy with morphine and ketamine. One of the earliest of these studies (Galinski 2007) enrolled patients with “severe acute pain” following trauma, being transported by mobile intensive care units staffed by physicians. Patients received either morphine and ketamine, or morphine alone. They demonstrated similar reductions in pain scores at 30 minutes with higher morphine consumption (0.2 mg/kg vs. 0.15 mg/kg) among those not receiving ketamine. Notably, the incidence of neuropsychological adverse effects was much higher among those receiving ketamine (36% vs. 3%).
A study out of the Rhode Island Hospital ED (Beaudoin 2014) compared the use of morphine alone to the use of morphine with two different doses of ketamine (0.15 mg/kg and 0.3 mg/kg) among patients with moderate to severe acute pain. Twenty patients were enrolled in each group, and they found that pain reduction was better among those receiving ketamine, with no difference in pain reduction between the two ketamine groups. Oddly, the amount of rescue analgesia provided was not different among the three groups, suggesting that perhaps those patients receiving only morphine were inadequately treated, which may account for the differences observed in the primary outcome, rather than a benefit due to ketamine. Length of stay was over half an hour longer in the two ketamine groups than it was among those receiving morphine only.
A third study, conducted in Isfahan, Iran (Majidinejad 2014), enrolled 126 patients with long bone fractures, randomizing them to receive either morphine or ketamine (here at a rather high dose of 0.5 mg/kg). They looked at pain control just 10 minutes after drug injection, and found similar rates of pain control, with a successful decrease in pain severity seen in nearly all patients in both groups at 10 minutes (93.7% of patients in the ketamine group and 96.8% in the morphine group). Almost 10% of patients receiving ketamine developed emergence phenomena, while no adverse effects were seen in those receiving morphine. This study did a poor job reporting data according to Consort guidelines, making interpretation of the results difficult.
The finally study out of Maimonides Medical Center in Brooklyn, NY (Motov 2015) enrolled 90 patients with acute abdominal, flank, back, or musculoskeletal pain, and randomized them to receive either morphine or ketamine (0.3 mg/kg). They found no difference in the primary outcome, reduction in pain at 30 minutes, but did demonstrate a significantly higher need for rescue analgesia with IV fentanyl at 120 minutes.
While these studies certainly confirm the analgesic effects of IV ketamine in patients with acute pain, they do not necessarily demonstrate a benefit over typical IV opiate administration. Instead, there seems to be a higher incidence of adverse effects (primarily dysphoria), increased ED length of stay, and a potentially greater need for rescue analgesia, likely owing to the relatively short duration of action of ketamine. Unfortunately, patients for whom we would typically consider ketamine as an alternative to opiates due to concerns regarding respiratory or cardiac depressive effects (i.e. the elderly, those with pulmonary compromise, or those with unstable vital signs) were understandably excluded from all of these studies. While it seems biologically plausible that ketamine would provide adequate analgesia in such patients with a reduction in the risk of major adverse events, there is currently no data in the literature to directly support this (external validity).
Age-Adjusted D-Dimer to Rule Out Pulmonary Embolism
Apr 07, 2016
Show notes
Journal Club Podcast #29: February 2016
A monologue on the ins and outs of using an age-adjusted D-dimer to rule out pulmonary embolism in patients over 50...
You are working in a community ED one afternoon when you encounter Mrs. X, a pleasant 65-year old woman with a history of hypertension and osteoporosis, who is in town visiting her grandchildren from California. She flew in 2 days earlier, and for the last 12 hours has noted some right-sided, pleuritic chest pain. She thinks she pulled a muscle picking up her 3-year old grandson, but was worried and wanted to be evaluated.
Her physical exam is unremarkable, including a heart rate of 70, a normal oxygen saturation on room air, and a normal respiratory rate. Her lungs are clear and she does seem to have pain with deep inspiration. There is no chest wall tenderness, no LE swelling, no LE cords, and no calf tenderness.
Given her recent plane trip you are concerned about a possible PE. Having attended a journal club on reducing PE protocol CT ordering rates during residency, you calculate her Well's score and find that she is low risk, so order a D-dimer in addition to an ECG and chest x-ray. The ECG and CXR are normal, but the D-dimer is elevated at 600 mcg/mL FEU. You explain to the patient that she will need to have a CT scan to evaluate for a PE, at the same time remembering that you've heard about age-adjusted D-dimer. You wonder if you could adjust the upper limits of normal for this patient, given her age, and hence obviate the need for the CT.
Too busy to look this up now, you continue your shift. The CT comes back negative and you discharge the patient on NSAIDs, but after your shift, you decide to look more closely at the evidence.
PICO Question:
Population: Patients aged > 50 years with a clinical suspicion of PE and non-high pre-test probability.
Intervention: An age-adjusted D-dimer cutoff.
Comparison: A conventional D-dimer cutoff.
Outcome: Sensitivity, specificity, likelihood ratio, false negative rate, and decrease in additional confirmatory testing (CT, VQ scan).
Search Strategy:
PubMed was searched using the terms “age adjusted d-dimer” (http://tinyurl.com/jfa4t62). This resulted in 148 articles, from which the following 4 were selected.
Bottom Line:
In patients who are not high-risk for pulmonary embolism, D-dimer has been shown to be effective at ruling out disease. Unfortunately, this test also has a low specificity and a high false-positive risk. This risk increases (and specificity decreases) substantially with increasing age. The specificity decreases incrementally with each decade increase in age, from around 67% in patients < 50 years of age to nearly 15% in those over 80 (Schouten 2013). As a result, some have proposed adjusting the D-dimer cutoff based on age. A derivation study using prospective cohorts of 1721 patients from Switzerland and France determined that the Age (years) * 10 µg/L was the optimal cutoff for patients over 50 (Douma 2010). This formula assumes the use of an assay that reports results in fibrinogen equivalence units (FEU) with a standard cutoff of 500 µg/L. This same study attempted to validate this formula in two similar European patient cohorts, resulting in 11.2% (95% CI 9.3-13.3%) and 18.2% (95% CI 15-21.4%) increases in the number of patients with a negative D-dimer in each of the cohorts, with very small increases in the rates of missed PE (0.4% and 0.2%, respectively). The major limitation of this study was that all of the cohorts were comprised of fairly homogenous Western European patients.
A retrospective study conducted using medical records from Kaiser Permanente Southern California (Sharp 2016) demonstrated an increase in the specificity of D-dimer in patients over 50 years of age from 54.4% (95% CI 53.9-55.0) using the standard cutoff to 63.9% (95% CI 63.4-64.5) using this age-adjusted cutoff. While this was accompanied by a decrease in sensitivity from 98.0% (95% CI 96.4-84.2) to 92.9% (95% CI 90.3-95.0), the overall negative likelihood ratio of the age-adjusted cutoff was 0.11 (95% CI 0.08-0.15) suggesting a significant ability to rule out disease in non-high risk patients. A systematic review and meta-analysis demonstrated an even better ability to rule out PE, with a negative likelihood ratio of 0.05 in patients over 50 years of age (Schouten 2013). The primary limitation of this meta-analysis was the significant risk of verification bias in all but one of the included studies.
Having thus been derived and validated in several different populations, the age-adjusted cutoff has also been evaluated in clinical practice (Righini 2014). In a study conducted at 19 hospitals in 4 countries in Europe (Belgium, France, Switzerland, and the Netherlands), the use of an age-adjusted cutoff resulted in an absolute decrease in the number of patients requiring additional testing of 11.6% (95% CI 10.5-12.9). Out of 331 patients with a D-dimer between the conventional cutoff and the age-adjusted cutoff, only one was later found to have a venous thromboembolism, for an overall failure rate of 0.3% (95% CI 0.1-1.7).
The use of an age-adjusted cutoff has therefore been shown to significantly reduce the need for further confirmatory testing in non-high patients, thereby reducing the risks associated with CT scanning (e.g. contrast-induced nephropathy [Mitchell 2010]). Unfortunately, this comes with a small, but not insignificant increase in the false negative risk, increasing the likelihood of missing a PE. Given the medicolegal atmosphere in this country, it will likely take some work to change clinical practice on a broad scale. The current clinical practice guidelines form the American College of Emergency Physicians (ACEP) makes only brief mention of adjusting the D-dimer cutoff for age, and does not make any recommendations regarding this practice. In order to change practice, there will likely need to be some support from our professional societies in this regard, as well as support from hospitals and physicians on other services (i.e. pulmonology, critical care, internal medicine, and hospitalists).
Finally, there are multiple D-dimer assays currently available using e a wide range of cutoff values to defined “normal” and “elevated” levels. Barnes-Jewish hospital currently uses the HemosIL D-dimer with an abnormal cutoff of 230 µg/L, which makes it difficult to adjust for age using the standard formula. Standardization of these assays, or the derivation of an age-adjusted cutoff for each assay, will therefore be necessary before we can adjust our concepts of normal and abnormal at institutions that do not use an assay with a cutoff of 500 µg/L.
Sterile vs. Non-sterile Gloves for Laceration Repair
Mar 09, 2016
Show notes
Journal Club Podcast #28: January 2016 Chris Carpenter and Mike Willman get together to talk about sterile gloves, knowledge translation, and the slippery slope of evidence-based medicine... Click Tab to Expand Articles: 1st Years: Sterile Versus Nonsterile Gloves for Repair of Uncomplicated Lacerations in the Emergency Department: A Randomized Controlled Trial, Ann Emerg Med 2004; 43: 362-370. (http://pmid.us/14985664) 2nd Years: A pilot study on the repair of contaminated traumatic wounds in the emergency department using sterile versus non-sterile gloves, Hong Kong J Emerg Med 2014; 21: 148-152. (http://tinyurl.com/HongKongJEMGloves2014) 3rd Years: Comparing non-sterile with sterile gloves for minor surgery: a prospective randomised controlled non-inferiority trial, Med J Aust 2015; 202: 27-31. (http://pmid.us/25588441) 4th Years: Comparison of the Prevalence of Surgical Site Infection with Use of Sterile Versus Nonsterile Gloves for Resection and Reconstruction During Mohs Surgery, Dermatol Surg 2014; 40: 234-239. (http://pmid.us/24446695) Vignette: Mr. C. is a healthy 45 year old male who has been constructing a covered porch in his backyard (imagine it is springtime). While working on it earlier today, he tripped over a 2x4 and stumbled through a pane of glass. After getting up, he noticed that he had cut his right thigh. The brisk bleeding subsided after his wife held pressure with a towel for 15 minutes (he was unable to do so himself as he nearly fainted at the sight of his own blood). He did not hit his head or suffer any other injuries. Upon seeing the gaping wound, several centimeters long with subcutaneous fat poking through, she promptly brought him to the ED for stitches. In the ED, his vitals are BP 126/85, P 68, RR 18, T 37.1°C, and 100% oxygen saturation on room air. He is in no acute distress, and his exam is unremarkable, except for a 6cm laceration to his right lateral thigh. It is less than 1cm deep with only subcutaneous fat showing. X-ray shows no fractures or foreign bodies. There does not appear to be any muscle or tendon injury and he has full range of motion. The bleeding has stopped and sensation is intact throughout. There are no visible vessels, nerves, or foreign bodies on exploration. As you irrigate the wound with tap water (why tap water rather than normal saline? See July 2008 Journal Club and updated studies by Weiss 2013 and the Cochrane Collaboration), you carefully contemplate how you are going to repair it. You decide to use a 3-0 or 4-0 non-absorbable suture due to its location (but absorbable would arguably do as well, see February 2010 Journal Club). As you gather your supplies, your attending reminds to use sterile gloves and sterile technique while doing the repair. You remember that while doing other laceration repairs on previous shifts you have been told by some attendings that you needed to use sterile gloves, but others have said that using clean, non-sterile gloves worked equally well at less cost. You decide to learn what the literature has to say about sterile gloves for ED laceration repair. PICO Question: Population: Patients with acute, uncomplicated lacerations requiring closure in the ED Intervention: Use of clean, non-sterile gloves during laceration repair Comparison: Use of sterile gloves for laceration repair Outcome: Rate of wound infection after repair Search Strategy: You search Pubmed for “sterile nonsterile gloves laceration repair” and get two results, one of which is in German. You broaden your search to “sterile AND (nonsterile OR non-sterile) AND gloves” and get 96 results (see http://tinyurl.com/zzt97jy). Only one of these studies pertains directly to ED laceration repairs, but at least it is a randomized, controlled trial so Brian Cohn will be ecstatic about that. You also conduct a Web of Science search to find any additional non-PubMed archived studies that have referenced the single ED RCT on this topic and you find one additional study in the Hong Kong Journal of Emergency Medicine. Lacking more ED studies, you decide to incorporate additional studies that compare non-sterile and sterile gloves for “minor surgery”, since laceration repair is a sort of “minor surgery” and the results could reasonably be extrapolated to the ED setting. After reviewing the 96 abstracts, you select the following four articles to review in detail: Bottom Line: Suture repair of traumatic lacerations occur daily in EDs around the world. The objectives of laceration repair include restoration of skin integrity with adequate post-healing cosmetic appearance, minimization of functional impairment, and avoidance of infection. Risk factors for laceration infection include diabetes, increased age, laceration width, laceration location (infection risk lower on head/neck than elsewhere), and presence of a foreign body (Hollander 2001). Many “traditional” practices continue through dogma rather than on the basis of scientific validity. Historically, suture closure was the most common method used to repair lacerations in the ED (Baker 1990), but dogma is being replaced by evidence as summarized on Skeptics Guide to Emergency Medicine (in 2012 and again in 2014), SOCMOB Blog, Life in the Fast Lane, and Manu et Corde. In addition, past Washington University EM Journal Clubs have explored the evidence-basis to support absorbable sutures and tap water irrigation. The current Journal Club challenges the long-held belief (dogma) that sterile gloves are required when repairing lacerations in the ED to prevent post-repair wound infections. Research indicates that >105 organisms per mL are required to cause wound infection (Elek 1956, Robson 1973, Raahave 1986) in traumatic lacerations or post-op wounds. Although clean, non-sterile gloves carry a significantly higher bacterial load, the increased non-sterile glove bacterial load is not sufficient to cause infections (Creamer 2012). However, open boxes of gloves are more likely to carry bacterial contaminants, particularly when the gloves are wet (Luckey 2006, Hughes 2013). Sterile gloves at Barnes Jewish Hospital cost approximately $2.30 per pair versus $0.70 per pair of non-sterile gloves and in the busy ED frequent interruptions while suturing often translate into more than one pair of gloves being used. Therefore, an opportunity to reduce healthcare costs using non-sterile gloves during laceration repair exists. However, one 2003 Emergency Medical Journal Best Bets synopsis attempt to redefine a standard of care for ED wound repair using non-sterile gloves implied that insufficient evidence existed to ethically alter practice (Sage 2003). Despite that 2003 Best Bets review, several decades of research imply that using clean, dry, non-sterile gloves (or no gloves) in acute care settings do not increase post-repair infection rates. In fact, in 1982 Bodiwala et al. observed no increase in infection rates for 418 laceration repairs using bare hand (no glove) wound repair when comparing surgical gloves (207 wounds) with no gloves (210 wounds). Similarly, another study in the mid-1980’s using bare hands for 25 patients and surgical gloves for 25 patients did not increase the incidence of complications in rural primary care (Worrall 1987). In this month’s Journal club we critically appraised two ED-based studies, one primary care study, and a surgery study, each of which evaluated the risk of post-wound repair infection using non-sterile, clean gloves. Perelman 2004 A three hospital, Toronto ED-based, randomized controlled study which is both the most pertinent and the highest quality research to date on the topic of ED wound closure. The authors excluded 26% of patients with diabetes, renal failure, asplenia, immunodeficiency (acquired, congenital or immunosuppressive therapy), cirrhosis, keloids, current antibiotic use, treating physician perspective that prophylactic antibiotics were required (prosthetic heart valve, bites, contaminated wounds), high risk wounds (multiple trauma, open fracture, concomitant vascular, nerve or tendon injury, stab wounds, gunshot wounds, intra-articular wounds, animal and human bites, presentations >12 hours after injury, signs of infection at presentation, or suspected foreign body), or those who did not consent. They used explicit, previously defined criteria to define “wound infection” (Maitra 1986, Rutherford 1980, Gosnold 1977), cultured purulent infections at follow-up, and noted no increased risk of infection using non-sterile gloves. Critical concerns for this study that might limit confidence in the results included lack of reporting of physician-level characteristics (experience closing wounds), patient-level characteristics (health literacy, socioeconomic status), or system-level characteristics (access to primary care for follow-up wound care). Ghafouri 2014 This Iranian ED study was deemed too biased with incomplete statistical analysis to meaningfully inform the equivalency or non-inferiority of non-sterile gloves for traumatic, contaminated wound closure. Among the many flaws identified were · No blinding so significant potential for bias (skewed estimates of “truth” in observed outcomes) with biases by patients (ascertainment bias by better follow-up), physicians (co-intervention bias), or outcome assessors. · High lost to follow-up rates without any sensitivity analysis to explore the potential effect on results if those lost to follow-up developed wound infections. · No regression analysis to determine whether unequal distribution of confounders (age, limb, wound, sharp objects) accounted for differences in wound infection rate rather than sterile vs. non-sterile gloves. · No standardization of either wound repair (Irrigation? Topical antibiotic?) or how to reproducibly define if “wound infection” occurred. · Uncertain external validity to U.S. EDs (staffing of EDs, availability of outpatient follow-up). · No assessment of patient compliance with oral antibiotics. · No sample size calculation to quantify the risks of Type I and Type II error. · No confidence intervals presented so unable to assess precision. Heal 2015 This Australian primary care study evaluated skin biopsies with suture repair noting no association between non-sterile glove use and skin infection rates at the time of suture removal. These results should be extrapolated to ED traumatic incisions cautiously, since trauma-related incisions requiring suture repair are often contaminated, irregular, and closed several hours after skin opening. Mehta 2014 This Dermatology-surgeon study had limited applicability to ED laceration repairs: one surgeon performing thousands of Mohs Micrographic Surgery procedures did not detect significant change in SSI when using NSG. This has limited application to the average ED where many physicians repair traumatic lacerations that are frequently irregular, deep and contaminated. In additional, multiple flaws in this study included · No randomization or blinding so subject to observational trial bias. · No explicit definition of “wound infection” (for examples see Maitra 1986, Rutherford 1980, or Gosnold 1977) which could affect both the accuracy and the reliability of whether wound infection was present or absent. · Limited external validity to surgeons (only 1 surgeon performed every procedure) and to emergency medicine (different patients, different environment, and different injuries then Dermatology patients) so this is essentially an “N of 1” study for that surgeon. · Uncertain lost to follow-up. · No explicit methods for logistic regression (inclusion criteria, goodness of fit). · Incomplete reporting of p-values/confidence intervals and seemingly significant baseline prognostic differences between sterile glove and non-sterile glove groups. General concerns expressed by Journal Club attendees included 1) Fear of a “slippery slope effect” in ED procedures beginning with appropriate non-sterile glove use for immunocompetent, low-risk patients and then extrapolating this to non-sterile use on higher risk patients and/or inappropriate (non-evidence based) use with lumbar punctures and central lines. The consensus opinion was that is the role for clinical educator oversight, bedside procedural teaching, and trainee (and attending) understanding of the published research. 2) Uncertain role for Shared Decision Making between clinicians and patients regarding the use of non-sterile gloves for wound repair in appropriate patients. There was no consensus on this debate, but hope that the 2016 AEM Consensus Conference would better highlight appropriate scenarios for ED Shared Decision Making. However, there was consensus that if a clinician decides to use non-sterile gloves and a patient or family member asks why non-sterile gloves are being used that the provider should be able to explain the rationale and safety for this decision based on the available evidence. 3) Several attendees debated the true cost-savings of this penny pinching discussion since much more expensive decisions are made daily in every ED, ward, and ICU. However, most attendees felt that with the volume of laceration repairs occurring in most EDs with frequent task interruptions necessitating gloves to be changed in an era of transparent cost-containment, using non-sterile gloves on immunocompetent patients with low risk wounds is worth considering. Despite these concerns, the vast majority of attendees felt comfortable using non-sterile gloves for low-risk laceration repairs. In fact, most already were using non-sterile gloves based on their awareness on this topic from the social media world.
It’s another busy day TCC, when an elderly female rolls in from triage with fever, cough, and a new oxygen requirement. Her vitals are T 38.3 BP 90/42 , HR 115, RR 24, SpO2 88% on RA. Even before you see the patient you are concerned for pneumonia with severe sepsis. You institute early antibiotics, fluids, serial lactates and systematically begin to aggressively resuscitate her. The patient requires nearly five liters of normal saline before her blood pressure stabilizes. Proud of your resuscitation, you tweet out #crushingsepsis and #normalsaline4life which gets an immediate response from Dr. Evan Schwarz, who happened to be trolling your twitter feed. He tweets “More like #increasedrenalfailure and #trybalancedfluids”. Inspired by his tweets you perform a brief literature review on the topic of ‘balanced fluid’ resuscitation.
PICO Question:
Population: Critically ill adult patients (e.g. patients with severe sepsis or septic shock)
Comparison: Chloride rich fluids (e.g. normal saline)
Outcome: Mortality, renal failure, need for renal replacement therapy, cost, length of stay
Search Strategy:
No formal search strategy was used. Articles were chosen by Drs. Louis Jamtgaard and Evan Schwarz, in part based on research done for a recent article by Dr. Schwarz in EPMonthly.
Bottom Line:
Normal saline has long been the “go to” fluid of choice for resuscitation in the ED for critically ill patients. However, the use of such “chloride rich” or “unbalanced” fluids has been controversial for decades, with many calling for the use of fluids that more closely resemble the tonicity of human blood. For example, aggressive resuscitation with isotonic saline has been shown to decrease serum pH, without affecting serum osmolality (Williams 1999), and has been suggested to increase the risk of renal dysfunction (Lobo 2014). The clinical significance of these and similar effects has been called into question over the last decade. We sought to evaluate the evidence for and against the use of balanced fluid resuscitation in ED patients, particularly those with severe sepsis or septic shock.
Unfortunately, no articles addressing fluid choice in emergency department patients were identified. All four articles were conducted in the ICU, making it difficult to generalize the results to our patient population. The is especially true in two of the papers: in one of these only 22% of patients were admitted from the ED, half were post-operative, and nearly a third were admitted following elective surgery (Yunos 2012); in the other, patients were noted to be primarily post-operative, and the majority of these were following elective surgery (Young 2015). Neither of these studies demonstrated a reduction in acute kidney injury (AKI), need for renal replacement therapy, or mortality with the use of balanced fluids. While both studies were prospective, and the study by Yunos et al was randomized, the patients were overall less sick than patients traditionally admitted to the ICU from the ED, making it difficult to apply these results to our patient population (external validity).
Two less methodologically robust, retrospective studies were identified, that at least included patients more similar to those in our setting (Rhagunathan 2014, Rhagunathan 2015). These two studies were conducted using the same retrospective cohort of patients from 360 US ICUs with sepsis requiring vasopressor therapy. Unfortunately, as these were retrospective studies, the two treatment groups were unbalanced, and statistical methods had to be employed to balance the two cohorts. In the first of these studies, patients receiving any amount of balanced fluid were propensity matched to patients receiving only unbalanced fluids during the same time period. Patients who received some balanced fluids saw a decrease in in-hospital mortality (RR 0.86, 95% CI 0.78-0.94; NNT 31) with no difference in AKI or need for dialysis. A dose-response relationship was also observed, in which the relative risk of in-hospital mortality was lowered an additional 3.4% on average for every 10% increase in in the proportion of balanced fluids received. In the second study, multiple methods were used to adjust for baseline differences between groups, including propensity matching, inverse probability weighting, and logistic regression. Regardless of the method used, the use of balanced fluids was associated with a decrease in in-hospital mortality.
Unfortunately, there are no prospective, randomized trials in ED patients assessing the efficacy of balanced fluids in resuscitation. While there are theoretical benefits, none of these has yet been proven. The current data consists of a fairly methodologically sound, randomized trial and a before and after study, each conducted with a relatively healthy cohort of patients that seem quite disparate from critically ill patients in the ED, and two retrospective observational trials of septic ICU patients in which patients were treated at clinician discretion. While these two latter trials utilized statistical methods to attempt to balance known confounders between the groups, these methods do not replace randomization when evaluating their methodological rigor. The current evidence is fair at best, but with varying outcomes, making it difficult to provide a clear recommendation. Further prospective studies should be conducted using critically ill ED patients, in order to help us make better decisions regarding our fluid administration options, particularly in those patients undergoing large-volume resuscitation. Given the relatively few downsides to balanced fluid administration, it seems reasonable to opt for lactated ringer’s or Hartmann’s solution when administered a large volume of fluid to patient, particularly when such a patient may already be acidotic.
D-Dimer in the Diagnosis of Aortic Dissection
Nov 30, 2015
Show notes
Journal Club Podcast #26: October 2015
In which I sit down and discuss the use of D-Dimer to rule-out acute aortic dissection in low-risk patients...
You are moonlighting in a local community ED one afternoon—making serious bank and contemplating what to spend on that money on—when you encounter a forty-year old male patient with chest pain. He has a history of hypertension for which he takes lisinopril, but is otherwise completely healthy. He was watching TV earlier in the day, eating nachos, when he developed a fairly abrupt onset of dull pain in the center of his chest.
As you continue your HPI, you learn that the pain does, in fact, radiate into his back, but is not ripping or tearing. He has no neurologic deficits, has symmetric blood pressures in both arms, and has stable vitals (BP130/85, HR 79, RR 12, SpO2 98%).
You order and ECG, CXR, cardiac enzymes, a BMP, and CBC, all of which come back normal.
You are still considering an acute aortic dissection as part of your differential, given the radiation of pain to the back, but would prefer not to expose your patient to the risks of radiation and contrast unless absolutely necessary. Your suspicion is fairly low. You wonder if a D-dimer would be a reasonable test to rule aortic dissection in this patient. In the end, you get a CT scan, which is negative for dissection, and admit the patient for a stress test. When you get off work, you decide to search the evidence and see what you can find.
PICO Question:
Population: Adult ED patients with suspected aortic dissection
MedLine was searched via PubMED, using the strategy “D-dimer AND aortic dissection” resulting in 117 citations (http://tinyurl.com/omohgdl). Of these, one meta-analysis and 3 primary research articles were selected for inclusion.
Bottom Line:
Aortic dissection, while a relatively rare disease, carries with it a high mortality rate. Mortality for type A dissection is around 25% when managed with surgery, and this rate increases to nearly 60% when managed non-operatively (Hagan 2000). Mortality has been shown to increase substantially for every hour treatment is delayed (Mészáros 2000), making prompt diagnosis and management a key to a good outcome. Diagnosis of aortic dissection typically requires CT angiography, MRI, or trans-esophageal echocardiography (TEE). MRI and TEE are both time-consuming modalities, and TEE is typically quite invasive. While CT is relatively quick and noninvasive, it carries risks associated with both radiation exposure and with the administration of iodinated contrast dye. Therefore the possibility of a noninvasive, rapid screening laboratory test to rule-out aortic dissection is quite appealing.
D-dimer has been proven to accurately rule-out pulmonary embolism, but only when used properly. Low and possibly moderate-risk patients, as determined by a clinical decision rule such as the modified Well’s score or the Geneva score, with a negative D-dimer are felt to be at sufficiently low risk of PE that further testing is not needed (ACEP Clinical Policy).
D-dimer has also been proposed as a means of ruling out aortic dissection. A prior journal club on this topic found that D-dimer had a low negative likelihood ratio (0.06) and negative predictive value, but concluded that there was an absence of clinical decision rules (CDR’s) to determine pre-test probability, and hence to determine which patients could be accurately ruled out for dissection with a negative D-dimer alone. We therefore sought to determine if such CDR’s existed, and if an algorithm could be devised to used D-dimer to exclude aortic dissection in a subset of patients.
The aortic dissection detection (ADD) risk score, introduced in the American Heart Association 2010 guidelines, is a prospectively validated CDR, in which low-risk patients (ADD score = 0) have been shown to have a risk of disease of around 6%. Combined with a negative likelihood ratio of 0.05, as demonstrated in a recently published meta-analysis from the Annals of Emergency Medicine, a patient with an ADD score of 0 and a negative D-dimer would have a post-probability of disease of 0.3%. Of note, a large, prospective, multicenter trial found a similar negative likelihood ratio (0.07). A retrospective study out of Germany sought to evaluate this approach, and found that out of 376 patients being evaluated for aortic dissection, 127 (34%) had an ADD score of 0 and a negative D-dimer . None of these patients were found to have an aortic dissection. In a similar study from Italy, a prospectively collected registry was used to retrospectively evaluate the ADD score combined with D-dimer testing. Out of 1035 patients being evaluated for aortic dissection with a D-dimer level available, 92 (8.9%) had both an ADD score of 0 and a negative D-dimer, and none of these patients were found to have an aortic dissection. Among 152 patients with an ADD score of 1 and a negative D-dimer, only 2 (0.2%) were found to have an aortic dissection.
While these data are promising, suggesting that patients with an ADD score of 0 (and possibly 1) and a negative D-dimer are at extremely low risk of having an aortic dissection, some issues remain. To date, no prospective studies have evaluated the accuracy or safety of this approach, and should be conducted prior to more widespread implementation. Additionally, the test threshold—the probability of disease below which further testing is likely to cause more harm than benefit, but above which further testing is warranted—should be calculated in order to determine the cut-off at which we can safely exclude patients with a negative D-dimer alone. The Pauker and Kassirer method for calculating test and treatment thresholds is shown in figure 1, and relies on knowing the diagnostic test characteristics of more definitive testing, and the risks associated with the test, and the risks associated with treatment of the disease. Once this test threshold is known, and once the combined use of the ADD score and negative D-dimer has been prospectively shown to identify a subset of patients at sufficiently low risk of aortic dissection, an algorithm can be set in place to reliably exclude the disease without the risks of more definitive testing.
Intranasal Midazolam for Pediatric Status Epilepticus
Oct 22, 2015
Show notes
Journal Club Podcast #25: September 2015
Drs. Katie Leonard and Indi Trehan join me from Children's Hospital to talk intranasal drugs and pediatric seizures...
A 3 year-old male presents to the ED with his parents with a seizure. The patient has had 2 prior febrile seizures in the past. Parents note that he has been seizing for approximately 10 minutes. The triage nurse notes that the patient is actively seizing with generalized-tonic movements of all extremities, eyes rolled back, teeth clenched and unresponsive with peri-oral cyanosis. The patient is brought immediately back to a room.
His initial vital signs are: HR 144, BP 110/67, RR 14, SpO2 87% on RA. You provide oxygen for the patient with a 100% O2 by non-breather and optimize airway positioning. You order 0.1 mg/kg of IV lorazepam per the SLCH status epilepticus management guidelines.
2 nurses quickly attempt to place an IV and fail to obtain access x 3 attempts. You send someone to get the IO kit and ask for diastat (rectal diazepam). The nurse asks you how much Diastat you want to give and while you are trying to remember the age-based recommendations for dosing, you think about if there are any other options for delivery of a benzodiazepine without IV access. You remember that sometimes we give intranasal versed (midazolam) for sedation and wonder if that would work for seizures and be an acceptable alternative to Diastat.
You know that the effectiveness of anticonvulsants to terminate seizures decreases rapidly as the time between start of convulsions and drug administration lengthens, so you want to hasten your delivery of an anticonvulsant that works!
PICO Question:
Population: Pediatric patients in status epilepticus
Intervention: Intranasal midazolam
Comparison: Rectal diazepam
Outcome: Resolution of seizure activity, return to normal mental status, ED length of stay
Search Strategy:
MEDLINE was searched via PubMed using the terms “(Seizures OR status epilepticus) AND intranasal AND rectal” (tinyurl.com/puvvqx2). This resulted in 43 citations, from which the four most relevant articles were selected.
Bottom Line:
Rectal diazepam is commonly used in the management of pediatric seizures at home and by EMS personnel. Given issues with administration and dosing, some EMS systems have moved to alternative routes of benzodiazepine administration, including intranasal administration of midazolam (Holsti 2007).
A handful of studies have directly compared rectal diazepam to intranasal midazolam for the treatment of pediatric seizures. One hospital-based study from Israel demonstrated a decrease in the time from hospital arrival to treatment and faster seizure control with intranasal midazolam compared to rectal diazepam in children with febrile seizures (Lahat 2000), with no adverse events in either group. In a similar study from India involving both febrile and afebrile seizure patients, there was a mean decrease of around 18 seconds in the time to prepare and administer intranasal midazolam compared with rectal diazepam, and greater than 60 second mean decrease in time between drug administration and cessation of seizure activity (Bhattacharyya 2006); seizure cessation was more likely to have occurred within 10 minutes of drug administration in the intranasal midazolam group (RR 1.1, 95% CO 1.0 to 1.2). Finally, a Turkish study demonstrated a similar decrease in the rate of seizure cessation within 10 minutes of drug administration with intranasal midazolam (RR 1.5, 95% CI 1.0-2.2), along with a decrease in overall seizure duration and a decrease in the need for additional drug administration (Fisgin 2002).
These three foreign studies were all limited by small sample sizes (n = 52, 188, and 55, respectively), poor randomization technique, lack of blinding, lack of sample size calculation, and lack of primary outcome identification. In addition, there were several patient characteristics (such as a large proportion of patients with a history of birth asphyxia in Bhattacharyya et al) making it difficult to generalize the results to children in the US (external validity).
A single US study was identified from Salt Lake City that compared intranasal midazolam with rectal diazepam in the prehospital setting (Holsti 2007). Patients enrolled after a change in EMS protocol that mandated seizure treatment with intranasal midazolam were compared to historical controls. Patients receiving intranasal midazolam had a decrease in the duration of EMS-witness seizure activity (median 30 minutes vs. 11 minutes, p = 0.003), and total seizure time (median 45 minutes vs. 25 minutes, p < 0.001). Intranasal midazolam also led to lower overall hospital charges, decreased need for bag-valve mask ventilation, decreased need for intubation, and decreased need for hospital admission. This study was also limited by a small sample size (n = 57), as well as by a before-and-after study design, lack of randomization and blinding, and missing outcome data from the EMS records.
Overall, the evidence in support of the use of intranasal midazolam over rectal diazepam is limited and of poor quality, composed primarily of small, unblinded studies conducted in dissimilar populations with poor methodology. However, the evidence at least supports the premise that intranasal midazolam is safe and effective. It is reasonable, in light of this evidence, to use intranasal midazolam as an alternative to rectal diazepam in children with seizure activity, and may replace rectal diazepam for home treatment given its ease of administration.
Proton Pump Inhibitors in Upper GI Bleeding
Sep 13, 2015
Show notes
Journal Club Podcast #24: August 2015
Ramblings and musings about the benefits of proton pump inhibitors in the management of acute upper GI bleeds...
You're working a shift in EM-2 one day when you pick up a patient with the chief complaint of "bloody emesis." The patient is a 45 year old male with a history of chronic low back pain who takes daily naproxen (250 mg BID). His pain worsened two months ago when he was in an MVC, and he has been taking ibuprofen in addition to the naproxen. He began noticing epigastric abdominal discomfort 3 weeks ago, and last night began vomiting up coffee-ground emesis. This morning he had one episode of bright right emesis and decided to come to the ED.
He is hemodynamically stable, appears to be in no distress, and is not actively vomiting. He has mild epigastric abdominal tenderness, clear lungs, normal heart sounds without tachycardia, and his conjunctiva and skin do not appear to be pale. His hemoglobin is 13 and his PT/INR and PTT are normal. An NG tube is placed and returns coffee grounds with streaks of blood that do not clear after lavage with one liter of normal saline. You order a type and screen and cross him for 4 units (just in case).
You call the GI fellow, thinking that the patient probably needs an upper endoscopy. The GI fellow asks that you start the patient on a continuous infusion of intravenous pantoprazole. You wonder how useful IV proton pump inhibitors actually are in the setting of upper GI bleeds, and whether a continuous infusion (which ties up an IV and is rather expensive) is really necessary. The patient is admitted to the ICU with plans for an EGD later in the day. After you leave your shift you decide to look and see if there is any evidence out there on the use of PPIs in the management of acute upper GI hemorrhage.
PICO Question:
Population: Adult patients with undifferentiated acute upper GI bleeding
Intervention: Proton pump inhibitor (either IV or PO)
Comparison: Placebo
Outcome: Mortality, rebleeding rates, need for surgery, need for blood transfusion, ICU length of stay, hospital length of stay
Search Strategy:
A search of the Cochrane database using the term “proton pump inhibitor” resulted in a relevant meta-analysis from 2010. A search of PubMed using the strategy ("proton pump inhibitor" OR omeprazole OR pantoprazole OR esomeprazole OR lansoprazole) AND (bleed OR bleeding OR hemorrhage), limited to clinical trials in the last 5 years, yielded no additional relevant articles (http://tinyurl.com/q32oyaf). Three articles included in the Cochrane review were therefore chosen.
Much of this debate stems from a Cochrane systematic review and meta-analysis published on the subject in 2006, and later revised in 2010. In this systematic review, the authors found no effect on mortality (OR 1.12, 95% CI 0.75 to 1.68), rates of rebleeding (OR 0.81, 95% CI 0.62 to 1.06), the need for surgery (OR 0.90, 95% CI 0.65 to 1.25), or the need for a transfusion (OR 0.95, 95% CI 0.78 to 1.16). Despite this lack of a reduction in any patient-important outcomes, they did find a significant reduction in the stigmata of recent hemorrhage at endoscopy (OR 0.67, 95% CI 0.54 to 0.84). The main argument, therefore, stems from the acceptance of certain surrogate outcomes in place of patient-important outcomes.
In fact, the articles referenced in the meta-analysis tended to find similar results individually. Daneshmend et al (1992) found no difference in mortality, rebleeding, or need for transfusion, but noted a decrease in signs of bleeding at endoscopy. Hawkey et al (2001) found no reduction in death or rebleeding, but found a significant reduction in the presence of blood in the stomach at endoscopy. Finally, Lau et al (2007) found no difference in death or need for surgery, but did find a reduction in the need for treatment at the time of endoscopy (though all patients underwent endoscopy).
Surrogate outcomes have long been used in clinical research, offering several advantages such as lower cost, smaller sample size, and shorter follow-up. However, caution must be used when employing such outcomes. A validation is required before correlating an improvement in a surrogate outcome with an improvement in a patient-centered outcome. Complex statistical formulae have been proposed to make such a validation, such as those proposed by Prentice in 1987, but even these criteria have been called into question (Berger 2004). Equally important is the issue of determining the effect size for a patient-important outcome by using a surrogate outcome, even when the two have been shown to correlate. It has been shown, for example, that the use of surrogate outcomes tends to result in an overestimation of effect size when compared to studies using patient-important outcomes.
By demonstrating an improvement in surrogate outcomes without improvements in patient-important outcomes, the authors of these studies and of the Cochrane review all draw similar conclusions: that the data is limited but suggest that there may be a benefit to using a proton pump inhibitor for upper GI bleeds. The American College of Gastroenterology draws a similar conclusion in its guideline: “Pre-endoscopic intravenous proton pump inhibitor (PPI)…may be considered to decrease the proportion of patients who have higher risk stigmata of hemorrhage at endoscopy and who receive endoscopic therapy. However, PPIs do not improve clinical outcomes such as further bleeding, surgery, or death (Conditional recommendation, high-quality evidence).” This recommendation seems reasonable, and given the few downsides to proton pump inhibitors, their administration is likely worthwhile, as long as it does not interfere with other, potentially more important, interventions (i.e. resuscitation of critically ill patients, reversal of anticoagulation, or blood transfusion in symptomatic anemic patients).
Endovascular Therapies in the Management of Acute Stroke
Jun 26, 2015
Show notes
Journal Club Podcast #23: May 2015
Dr. Peter Panagos, director of neurovascular emergencies at Washington University, joins me to talk about Mr. Clean, Mr. Rescue, ESCAPE, and whole lot of other great acronyms...
A 67 year old white female presents to a moderate sized community hospital (also a Primary Stroke Center) 90 minutes after the onset of right-arm and leg hemiplegia as well as aphasia. The initial NIH Stroke Scale (NIHSS) is 13. A non-contrast head CT is negative, though there is a possible hyperdense "MCA sign" per the preliminary read. All labs are unremarkable and no contraindications to IV thrombolysis were elicited. The local emergency physician and neurologist agree that the patient is a good candidate for IV tPA. The risk and benefits are discussed but the family had some excellent questions. As the expert at the regional Comprehensive Stroke Center, you are contacted for your opinion. The patient’s son happens to be a family practitioner and has heard about some new interventional therapies that have been studied, including several studies recently published in the New England Journal of Emergency Medicine.
The family poses the following questions:
1. Are the new endovascular studies now the new standard of care for acute stroke care?
2. Does the patient really need to get IV tPA locally? Can she just be transported to the regional stroke center for endovascular therapy?
3. How do you know which patients will benefit from endovascular therapy? Can you predict who will do well?
4. Can every stroke center perform this therapy? Why does she need to go to a larger center?
5. How much better are these new therapies compared with standard IV therapy?
PICO Question:
Population: Adult patients with acute ischemic stroke
Intervention: Intra-arterial clot retrieval or intra-arterial thrombolysis
Comparison: Standard of care
Outcome: Functional status, mortality, quality of life
Search Strategy:
No formal search was conducted. Three recent positive articles and one negative article from 2013 were selected by Dr. Peter Panagos, an expert in neurologic emergencies.
Bottom Line:
In 2013, the stroke world was turned on its ear by the publication of three articles - all in the same issue of the New England Journal of Medicine - that showed no benefit to endovascular therapy in the treatment of acute stroke (IMS-III, SYNTHESIS, and MR RESCUE). While some felt this to be the final nail in the coffin for endovascular treatment, others felt that issues with inclusion criteria and treatment strategies may have negated any potential benefit of treatment.
In the SYNTHESIS trial, patients were randomized to either endovascular treatment or intravenous (IV) t-PA, rather than being eligible to receive both therapies. In both SYNTHESIS and IMS-III, patients were selected based solely on clinical data, and no radiologic assessment was made to verify large vessel occlusion. Finally, MR RESCUE excluded patients who were eligible for IV t-PA and also extended eligibility to 8 hours from symptom onset.
As a result of these proposed limitations (lack of proper confirmation of large vessel occlusion using either CT angiogram or MR angiogram, exclusion of patients eligible for IV t-PA, and inclusion of patients with prolonged symptoms) further research was planned and has been conducted to attempt to identify an appropriate subset of patients for endovascular therapy.
Three positive studies were published earlier this year. All three trials included only patients with imaging-confirmed occlusion of a large artery in the anterior cerebral circulation.
The first of these was MR CLEAN, which was conducted in the Netherlands and included patients who could receive endovascular treatment within 6 hours of symptom onset. The result was a favorable shift in the distribution of the modified Rankin scale in favor of endovascular treatment, with an adjusted odds ratio of 1.67 (95% CI 1.21 to 2.30).
The second article, ESCAPE, placed an emphasis on “fast treatment times and efficient work-flow.” This trial was stopped early for a perceived benefit, demonstrating a common odds ratio of 2.6 (95% CI 1.7-3.8) for an improvement of 1 point on the modified Rankin scale, favoring the intervention.
The third trial, SWIFT PRIME, was also stopped early for perceived benefit. Patients were eligible if endovascular therapy could be initiated within 6 hours of the time they were last seen normal. This study demonstrated a shift towards more favorable outcomes on the modified Rankin scale associated with endovascular treatment (p < 0.001). The calculated number needed to treat to have one patient have a "less-disabled outcome" was 2.6.
Two additional studies have been published in the last year: REVASCAT and EXTEND-IA. These studies also required imaging-confirmed large proximal vessel occlusion in the anterior circulation for enrollment. Both studies were also stopped early for perceived benefit, and both demonstrated improved functional outcomes at 90 days.
Finally, two additional studies have been completed, but have not yet been published. The THRACE trial had positive results, while the THERAPY trial resulted in clinical equipoise. Both of these trials were halted early based on the results of MR CLEAN.
Despite the rousing success of these more recent trials, there is still a great deal of controversy surrounding endovascular treatment. Some argue that the prior negative results simply can not be ignored, pointing out that previous negative studies raise the bar for statistical success in subsequent trials. Others have argued that the use of an ordinal analysis of the modified Rankin scale in many of these subsequent studies raises the possibility of erroneously detecting a benefit when one does not truly exist, given the limited reliability of the scale. Finally, two of these more recent studies were stopped early for benefit at unplanned interim analyses, raising the possibility that benefit was detected that would not have been found had the studies been completed.
On the other hand, proponents of endovascular therapy point out that the more recent studies used more strict inclusion criteria and protocols - including more timely intervention - than the original studies. It should also be pointed out that the largest of these trials (MR CLEAN) was not stopped early. Finally, ordinal analysis has become a common statistical tool in stroke trials, and has been accepted as a means of identifying smaller (but clinically significant) differences in outcomes than using a dichotomous cutoff for the modified Rankin scale.
Both sides in the debate over endovascular therapy for stroke make salient points. The current tide, however, seems to be in favor of its proponents. Many institutions have begun to perform endovascular procedures, with strict protocols guiding eligibility, including imaging-confirmation of large vessel occlusion. This practice will have far-reaching implications, including an impact on EMS transport and inter-hospital transfer to stroke centers. The data will need to be carefully considered, not only with respect to the treatment of individual patients, but also the broader impact on our healthcare system.
Routine Laboratory Screen in Psychiatric Patients in the ED
May 08, 2015
Show notes
Journal Club Podcast #21: April 2015
I contemplate the necessity of routine laboratory testing for psychiatric patients presenting to the emergency department...
You are working a shift in EM-1 (i.e. the corner of pain) one typical Friday the 13th. The moon is full and so are rooms 5-12. Three new psychiatric patients are brought in by EMS. The first is a 23 year-old female with a known history of schizophrenia, medication noncompliance, and chronic cocaine abuse who was found wandering the street acting paranoid and delusional. Her vital signs are normal. The second is a sixty year male whose wife passed away one year ago who has been feeling sad and depressed ever since. He states he wants to kill himself and owns a gun. He denies alcohol or drug use and does not appear intoxicated. His vitals are completely normal. The third is a thirty-five year old male with no known psychiatric medical history. His wife called EMS because he has been behaving more bizarrely for the last week, claiming the FBI was out to get him, claiming their children were aliens, and claiming she was the anti-Christ. He had barricaded himself in his room and the police had to assist in his extraction. He is tachycardic, but otherwise has normal vitals.
You know that you will need a psychiatric consult on all of these patients and start to order the "typical" labs, when you stop and wonder if this is really the best practice. You have three very different patients with very different differentials, and you wonder if the cookie-cutter method is really the best. You ask yourself if there is any literature to guide your decision making, specifically if there is any evidence that routine lab testing is beneficial in psychiatric ED patients. The next day you decide to perform a literature search and find...
PICO Question:
Population: Pediatric and adult patients presenting to the ED for evaluation of psychiatric chief complaints
Intervention: Routine laboratory screening
Comparison: Laboratory testing based on clinician discretion
Outcome: Disposition, psychiatric care, change in medical management, cost, length of stay
Search Strategy:
A PubMed search was conducted using the terms ((emergency) AND ((psychiatry) OR psychiatric)) AND ((routine) OR screening) in the title or abstract, limited to humans (http://tinyurl.com/kyo95e5). This resulted in 252 articles, from which 4 were chosen for inclusion.
Bottom Line:
Patients presenting to the emergency department (ED) with psychiatric complaints typically undergo a process of medical clearance prior to evaluation by a psychiatrist or psychiatric intake nurse. The nature of this “medical clearance” is seldom standardized. In addition to a history and physical exam, laboratory testing is often performed. What additional laboratory testing should be performed, if any, is a highly controversial topic and often varies from state to state and hospital to hospital. A retrospective analysis of adult psychiatric patients presenting to ED’s in Rhode Island demonstrated there was significant variability in the number tests performed at each hospital. The Illinois Department of Human Services specifically requires all patients to have blood counts, electrolytes, a pregnancy test, and a drug screen performed for medical clearance, while the state of New Jersey specifies that “diagnostic testing should be conducted based upon the emergency provider’s determination of need.”
The American College of Emergency Physicians Clinical Policy on the management of psychiatric patients in the ED recommends that laboratory testing be “directed by the history and physical examination,” noting that routine testing is “very low yield.” The results of our journal club support these recommendations for both adult and pediatric patients. A retrospective study of patients admitted to the Medical College of Georgia demonstrated only one significant laboratory abnormality that would change ED intervention or disposition out of 519 cases reviewed. This abnormality involved a patients with abnormal vital signs and a significant past medical history, and should have been expected based on the history and physical exam. A similar study in Bakersfield, CA demonstrated that only 4 patients without significant findings on the history and physical exam had a laboratory abnormality requiring a change in management. In all 4 cases, the lab abnormality was a positive urinalysis suggesting infection, and disposition was not altered in any of the cases.
In a randomized controlled trial conducted at San Francisco General Hospital, patients referred to the emergency psychiatric service were randomized to either mandatory drug screening or screening at physician discretion. Mandatory drug screening was found to have no impact on disposition or referral for substance abuse treatment. This study suggest that clinician discretion, rather than protocol, should dictate whether a urine drug screen is necessary for patients being evaluated by psychiatry in the ED.
Similar results to those discussed for adult patients have also been demonstrated in the pediatric population. In a retrospective chart review of pediatric patients presenting to a large inner city ED in California, lab testing resulted in a change in disposition in less than 1% of cases. In all but one of these cases, there was an associated abnormality in the history or physical exam that predicted the lab abnormality. In the other case, the abnormality was a positive pregnancy test, resulting in admission to the medical service where no pregnancy-related interventions were required. In another 6% of cases, there was a lab abnormality that required a change in management. In half of these cases, there was an associated abnormality in the history or physical exam; in the the other half, the abnormality involved a non-urgent change in medical management. The ED length of stay was significantly shorter in patients who did not undergo blood testing and in those who required no screening labs at all.
These data suggest that in alert, cooperative patients - both adult and pediatric, -routine laboratory testing for psychiatric complaints in the ED is unnecessary. Testing should instead be directed by the history and physical exam. Urine drug testing, while often useful in the long-term management of patients, does not appear to alter the acute disposition of patients, and should not delay psychiatric consultation or disposition from the ED.
Albumin for Patients with Spontaneous Bacterial Peritonitis or Large Volume Paracentesis
Apr 17, 2015
Show notes
Journal Club Podcast #21: March 2015
A few of the residents join me to discuss the benefits of albumin administration for patients with SBP or those undergoing large volume paracentesis...
You are caring for a fifty-year old gentleman with a history of non-alcoholic steatohepatitis with cirrhosis who presents to the emergency department (ED) with increased abdominal distension, shortness of breath, and fevers. His abdomen is distended and tense with mild diffuse tenderness. His temp is 38.7 C, BP is 103/60, HR is 89, and SpO2 is 99% on room air. You check his labs and find a WBC of 13.4, baseline anemia, a creatinine of 1.2, and an INR of 1.4. His chest x-ray reveals small lung volumes without infiltrates or pulmonary edema. A bedside ultrasound reveals a large amount of ascites. You decide to perform both a therapeutic paracentesis to relieve pressure on his diaphragm and improve his respiratory complaints, and send fluid to the lab for cell count, differential, gram stain, and culture given your concern for spontaneous bacterial peritonitis (SBP).
You manage to drain just over 8 liters of fluid, for which the patient is quite thankful. The fluid gram stain reveals abundant polymorphonuclear cells (PMNs) with no organism seen. The cell count reveals 15,000 nucleated cells, of which 89% are PMNs. You feel confident that the patient has SBP and order a dose of cefotaxime. You are admitting the patient to the medicine service when the resident suggests that you administer albumin. She tells you that the American Association for the Study of Liver Diseases (AASLD) recommends albumin administration both following large-volume paracentesis and in the management of select patients with SBP. You follow the resident’s recommendations, but are curious what the evidence actually shows. After your shift you decide to begin your literature search.
PICO Question:
#1
Population: Adult patients with cirrhosis and tense ascites undergoing large volume paracentesis
Two MEDLINE searches were conducted via PubMed. A search was performed using the terms albumin AND "spontaneous bacterial peritonitis" which resulted in 230 citations (http://tinyurl.com/l2zy2se). Of these, one systematic review and one large randomized controlled trial were chosen. An additional search was conducted using the terms albumin and paracentesis (http://tinyurl.com/kfau542). This resulted in 414 citations, from which two systematic reviews were chosen.
Bottom Line:
Ascites is one of the many complications associated with hepatic cirrhosis, and is associated with a poor prognosis (D’Amico 2006). Ascitic fluid can accumulate to the extent that it impairs functional status, and current guidelines recommend a large volume paracentesis for patients with tense ascites. When such large volumes of ascitic fluid are removed, fluid shifts and a decreased systemic vascular resistance can potentially lead to circulatory dysfunction, hyponatremia, and renal impairment (Lindsay 2014). The administration of intravenous albumin can theoretically reduce the risk of these complications, though this practice remains controversial (Manzocchi 2012, Caraceni 2013).
Two systematic reviews and meta-analyses published on the use of albumin following large volume paracentesis found similar results (Bernardi 2012, Kwok 2013). The use of albumin was shown to significantly reduce the risk of circulatory dysfunction, with a number needed to treat (NNT) of 2, and the risk of hyponatremia, with a NNT of 8. For these outcomes, albumin was shown to outperform other volume expanders as well. Albumin was not, however, shown to reduce mortality, renal impairment, ascites recurrence, or hospital readmission. While this evidence suggest some benefit to albumin administration, the two outcomes for which albumin demonstrated an improvement are of unclear clinical relevance. As a result, it is difficult make a strong recommendation either for or against albumin administration in patients undergoing large volume paracentesis. The current recommendation from the American Association for the Study of Liver Disease (AASLD) is to consider the administration of albumin (6-8 g/L of fluid removed) for patients undergoing removal of greater than 5 liters. This recommendation is appropriately given a low grade (IIa/C).
With regards to albumin administration in patients with SBP, the evidence is more compelling. A meta-analysis of 4 randomized controlled trials comprising 288 patients found significant reductions in both the risk of renal impairment (OR 0.21, 95% CI 0.11-0.42) and mortality (OR 0.34, 95% CI 0.19-0.60) with NNTs of 4 and 5, respectively. The included studies were, admittedly, of only moderate quality, with only one of them being blinded. The largest of these trials (Sort 1999), which included nearly half of the patients in the meta-analysis, independently demonstrated significant reductions in renal impairment (OR 0.21) and both in-hospital and 90-day mortality (ORs of 0.26 and 0.41, respectively). This study was not blinded, and more importantly was limited by a difference in baseline bilirubin levels between the two group: the mean bilirubin in the control group was 6 ± 1 compared to 4 ± 1 in the group that received albumin. This difference is important, as the study demonstrated on multivariate logistic regression that elevated bilirubin levels were independently predictive of a higher risk of both renal impairment and death.
Despite this limitation, the AASLD recommendation is to administer albumin (1.5 g/kg within 6 hours of diagnosis of SBP followed by 1.0 g/kg on day 3) in patients with a serum creatinine > 1 mg/dL OR BUN > 30 mg/dL OR bilirubin > 4 mg/dL. It should be noted that the limited administration based on these laboratory abnormalities is based on a single observational cohort study, and seems somewhat arbitrary.
Both therapeutic and diagnostic paracentesis are common procedures in emergency medicine, and the diagnosis and initial management of SBP fall well within our practice parameters. Given the increased boarding times observed in many EDs, it is prudent that the emergency physician be aware of treatment modalities that require initiation within the first several hours of patient care. As a result, it seems reasonable to begin the administration of albumin to patients with SBP concomitantly with antibiotics while the patient is still in the ED, as this has been shown to decrease the risk of both renal impairment and mortality. It is also reasonable to consider albumin infusion in patients undergoing large volume paracentesis (more than 5 liters of ascitic fluid removed), though the evidence in support of this is much less compelling.
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