Journal Feed Weekly Wrap-Up

We always work hard, but we may not have time to read through a bunch of journals. It’s time to learn smarter. 

Originally published at JournalFeed, a site that provides daily or weekly literature updates. 

Follow Dr. Clay Smith at @spoonfedEM, and sign up for email updates here.


#1: Off-Label Gabapentin and Pregabalin – Sketchy Evidence

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Gabapentinoids play a limited role for specific types of neuropathic pain, and pain reduction is modest at best. Side effects of dizziness, somnolence, and gait problems occur frequently.

Why does this matter?
Gabapentin was initially intended and marketed as an anticonvulsant. It is now mainly used for pain, but the only FDA approved use is post-herpetic neuralgia (PHN). Pregabalin has broader FDA approved uses that include PHN or neuropathic pain from diabetes, spinal cord injury, or fibromyalgia. Pfizer, the manufacturer of gabapentin and pregabalin, has been fined repeatedly for improper marketing of off-label uses. The history of gabapentin trials leading to approval for pain control is sordid and showed questionable tactics including, “planning to suppress unfavorable study results” and selective outcome reporting. See the NEJM exposé, which found that in, “8 of the 12 reported trials, the primary outcome defined in the published report differed from that described in the protocol.” Both these drugs are frequently used off-label. What is the evidence for such use?

Lady Gaba
Considering gabapentin for diabetic neuropathy, there were 5 RCTs reviewed, 2 of which showed no benefit. Three showed a decrease on a 0-10 pain scale by 1.1 to 1.9; a decrease in pain by at least 1 is considered clinically significant. A Cochrane review found the NNT was 6 for diabetic neuropathy pain. For other types of neuropathic pain (other than post-herpetic neuralgia or diabetic neuropathy), there is little evidence that gabapentin produces clinically significant pain reduction, except perhaps spinal cord injury (a single RCT with 20 total patients). Use of either gabapentinoid for sciatica doesn’t reduce pain. Evidence for pregabalin showed no benefit for these off-label painful conditions: central neuropathic pain, HIV neuropathy, unspecified neuropathy, acute zoster, chronic prostatitis, burns, or sickle cell pain. Pregabalin for chronic pancreatitis or traumatic nerve injury showed statistically but not clinically significant decreases in pain (i.e. <1 on a 0-10 scale).

Given that the primary evidence not very compelling, it’s unfortunate that meta-analyses and guidelines tend to generalize and even overstate the effectiveness of gabapentinoids. Finally, these drugs are not benign — dizziness, somnolence, and gait disturbance are common. “The number needed to harm for each adverse effect has ranged from roughly 3 to 11.” This is especially important among the elderly and those on other sedating medications. Also, there is growing recognition of abuse potential with gabapentinoids. Opioid-related deaths increase when patients are taking concomitant gabapentinoids.

These drugs have a limited role, but their effectiveness at reducing specific neuropathic pain syndromes is modest at best. Consider the side effects, cost, and likelihood of effectiveness when using them.

Source
A Clinical Overview of Off-label Use of Gabapentinoid Drugs. JAMA Intern Med. 2019 Mar 25. doi: 10.1001/jamainternmed.2019.0086. [Epub ahead of print]

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#2: RIFTS RCT – Restrictive Fluid in Septic Shock

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A restrictive fluid approach (<60mL/kg/72h) vs standard care had no impact on 30-day mortality or other adverse secondary outcomes in this pilot study of patients with severe sepsis or septic shock.

Why does this matter?
CENSER was a small RCT that showed early pressors improved shock control. CLOVERS is currently underway to test whether a restrictive fluid/early pressor approach vs a more liberal fluid approach improves mortality. This study looks purely at the impact of restricting fluid. For context, the original EGDT trial gave 168 mL/kg in the first 72 hours. That’s a lot.

Opposite of – “You gotta swell to get well”
This was a small, single system, two-hospital RCT with 109 patients with severe sepsis or septic shock (Sepsis 2) randomized to either restrictive fluid (<60mL/kg in 72h) or standard care. The restrictive group received significantly less fluid (47.1 mL/kg in 72h) than the standard care group (61.1 mL/kg in 72h). An important side note: both groups received about half as much fluid compared to what was administered in ARISE, ProMISe, and ProCESS. In the present study, there was no difference in 30-day mortality, nor was there any difference in organ failure, length of stay, or other adverse secondary outcomes. The restrictive fluid group spent 21 fewer hours on mechanical ventilation compared to usual care (16.8, 95%CI 7.0–26.5 vs 37.8, 95%CI 22.0–126.5; p= 0.02). This was a single center small study, considered a safety pilot for a larger trial. But the pendulum is already swinging toward less fluid. I was always taught during residency to pound patients with fluid. One of my attending physicians said, “You gotta swell to get well.” My…how things change.

Source
The Restrictive IV Fluid Trial in Severe Sepsis and Septic Shock (RIFTS): A Randomized Pilot Study. Crit Care Med. 2019 Apr 12. doi: 10.1097/CCM.0000000000003779. [Epub ahead of print]

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#3: New IDSA Guideline on Asymptomatic Bacteriuria

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The IDSA now only recommends screening for and treating asymptomatic bacteriuria (ASB) in pregnant women and those undergoing an invasive urologic procedure.

Why does this matter?
ASB is common in healthy women and patients who have had urologic abnormalities. This is an update to the 2005 version. The IDSA highly values prevention of antibiotic associated complications, such as C. difficile colitis and antimicrobial resistance. So, they have limited conditions for which screening and treatment is warranted. ASB is defined as – “1 or more species of bacteria growing in the urine at specified quantitative counts (≥10^5 colony-forming units [CFU]/mL or ≥10^8 CFU/L), irrespective of the presence of pyuria, in the absence of signs or symptoms attributable to urinary tract infection (UTI).”

Don’t worry – urine is sterile…or not
The only people for whom the IDSA recommends screening and treatment are pregnant women and those undergoing an invasive urologic procedure.

  • Should ASB Be Screened for and Treated in Pregnant Women?
    Answer: Yes, with the shortest course of effective medication possible

  • Should Patients Undergoing Endourological Procedures Be Screened or Treated for ASB?
    Answer: Yes, targeted based on culture data prior to the procedure and only 1-2 doses just prior to surgery.


For all others, screening for and treating ASB is not recommended.

  • In an Older, Functionally or Cognitively Impaired Patient, Which Nonlocalizing Symptoms Distinguish ASB From Symptomatic UTI?
    Answer: They recommend no treatment, even in the presence of delirium or fall, if genitourinary symptoms, fever, and hemodynamic instability are absent.

  • Should Asymptomatic Bacteriuria Be Screened for and Treated in Pediatric Patients?
    Answer: No

  • Should ASB Be Screened for or Treated in Healthy Nonpregnant Women?
    Answer: No

  • Should ASB Be Screened for and Treated in Functionally Impaired Older Women or Men Residing in the Community, or in Older Residents of Longterm Care Facilities?
    Answer: No

  • Should Diabetic Patients Be Screened or Treated for ASB?
    Answer: No

  • Should Patients Who Have Received a Kidney Transplant Be Screened or Treated for ASB?
    Answer: No

  • Should Patients Who Have Received a Solid Organ Transplant Other Than a Renal Transplant Be Screened or Treated for ASB?
    Answer: No

  • Should Patients With Neutropenia Be Screened or Treated for ASB?
    Answer: They don’t know. It is unknown how often ASB occurs in patients with high risk neutropenia (<100 cells/mm3, ≥7 days’ duration). Patients with “low risk” neutropenia (>100 cells/mm3, ≤7 days, clinically stable) have risk similar to non-neutropenic patients.

  • Should ASB Be Screened for or Treated in Individuals With Impaired Voiding Following Spinal Cord Injury?
    Answer: No

  • Should Patients With an Indwelling Urethral Catheter Be Screened or Treated for ASB?
    Answer: No for both short and long term catheters, and they comment this likely equally applies for suprapubic catheters.

  • Should Patients Undergoing Elective Nonurologic Surgery Be Screened and Treated for ASB?
    Answer: No

  • Should Patients Undergoing Implantation of Urologic Devices or Living With Urologic Devices Be Screened for or Treated for ASB?
    Answer: No

Source
Clinical Practice Guideline for the Management of Asymptomatic Bacteriuria: 2019 Update by the Infectious Diseases Society of America Clin Infect Dis. 2019 Mar 21. pii: ciy1121. doi: 10.1093/cid/ciy1121. [Epub ahead of print]

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