Thursday, September 21, 2017
To Treat or Not to Treat: Muscle Relaxants in Back Pain; Steroids in Pharyngitis; Aggressive IVF in Pancreatitis
Many thanks to Mike and Sarah Marynowski for hosting and to Matt DeStefani, Elisa Wing, Maddy Hawkins, Huu Tran, Jenny Denk and Jeff Florek for their outstanding analyses!
Article 1: Friedman BW, et al: Diazepam Is No Better Than Placebo When Added to Naproxen for Low Back Pain. Ann Emerg Med 2017;70:169-176.
In this double blind RCT, 114 patients with non-radicular, atraumatic acute low back pain without “red flag symptoms” treated at one urban health care system were either treated with naprosyn + diazepam or naprosyn + placebo. All patients received a teaching session about care of low back pain and were discharged from the ED. Seventy percent of patients in the diazepam group did take the diazepam one or more times daily. Primary outcome was improvement on a validated functional impairment survey, Roland Morris Disability Questionnaire (RMDQ), at one week. Secondary outcomes included pain intensity at 1 week and 3 months, frequency of pain, and frequency of analgesic use. A strength of this study was the use of these patient centered outcomes.
Results: Functional improvement as measured by the RMDQ at one week was exactly the same between the 2 groups. There were also no significant differences in the secondary outcomes, although trends favored placebo for both longer term improvement as well as for adverse events.
Limitations: There were a number of exclusion criteria, limiting generalizability. Results were susceptible to recall bias, as patients had to think back to prior symptoms. Dosing schedule was not rigid, although this mirrors real life.
Practice changing? Yes, for Elisa and Matt. It would be nice to have included a reliable assessment for muscle spasm, but the vast majority of these patients were felt to have muscle spasm by the practitioners. Unfortunately prior studies have demonstrated limited utility for other analgesics in treating low back pain. Yoga may help, acupuncture may help, and for uncomplicated low back pain, time helps; at 3 months 90% of patients had resolved pain.
Bottom line: Given the results of this and other prior studies, and the concern for impairment/abuse from using diazepam, only a minimal number of physicians at JC will plan to prescribe diazepam to this patient population. At best, they will reserve diazepam for severe spasm, and associated insomnia/anxiety.
Article 2: Hayward GN, et al: Effect of Oral Dexamethasone Without Immediate Antibiotics vs. Placebo on Acute Sore Throat in Adults: A Randomized Clinical Trial. JAMA. 20 I 7;8(317)1535-1543.
In this double blind RCT of 565 adult patients with acute pharyngitis deemed not to require immediate antibiotics and treated at 42 family practice sites in England, patients received either one dose of 10 mg oral dexamethasone or placebo. Primary outcome was complete resolution of symptoms at 24 hours. Secondary outcomes included complete resolution of symptoms at 48 hours, duration of moderately bad symptoms, and suppurative complications. The majority of patients did use OTC analgesics for symptom control. Rapid strep testing was not available, although 15% and 19% of patients in the 2 groups ended up with positive Strep cultures. Although complete resolution of symptoms at 24 hours may seem an unrealistic primary outcome, it has been used before and facilitated a high response rate.
Results: For the primary outcome, at 24 hours 23% of the dex group compared with 18% of placebo group achieved complete resolution of symptoms (RR 1.28, NNT = 20), which was not statistically significant. At 48 hours, there was a significant difference (35% in dex vs 27% in placebo) in complete resolution of symptoms (RR 1.31, NNT = 12). Results were similar for the 40% of patients offered a “delayed” antibiotic prescription vs. those not offered delayed antibiotics. There were no significant differences in any other secondary outcomes.
Limitations: The study was underpowered to detect differences in adverse outcomes. Potential adverse effects of increased steroid prescribing are uncertain. Patients in this study were young with good access to primary care.
Practice Changing? Huu and Maddy are not sold. While prior studies have demonstrated very positive effects for dexamethasone in patients with pharyngitis also treated with antibiotics, results in this trial of less severe pharyngitis were more modest.
Bottom line: Although the JC crowd would like to be able to offer additional symptom control to our patients with pharyngitis regardless of severity, indiscriminate use of dexamethasone was not supported, and most plan to reserve steroids for severe pharyngitis.
Article 3: Buxbaun JL, et al: Early Aggressive Hydration Hastens Clinical Improvement in Mild Acute Pancreatitis. Am J Gastroenterol 2017;112:797-803.
In this randomized trial of 60 patients with acute mild pancreatitis (no SIRS or organ failure), half received early “aggressive” IVF using LR with 20 cc/kg bolus followed by 3 cc/kg/hour vs. “standard” IVF with 10 cc/kg bolus followed by 1.5 cc/kg/hour. Patients were assessed at 12 hour intervals, with fluid adjustments and po status decisions based on HCT, BUN, creatinine, and pain level. Primary outcome was a combined endpoint at 36 hours of decreased HCT, BUN, creatinine; improved pain; and tolerance of oral diet. Secondary outcomes included the rate of clinical improvement, development of SIRS, development of severe pancreatitis, and volume overload (defined by physical exam).
Results: Significantly more patients in the aggressive fluids group had clinical improvement at 36 hours (70% vs. 42%, p=0.03, NNT=4), and persistent SIRS occurred less commonly with aggressive fluids (7.4% vs. 21%; OR=0.12, 0.02-0.94; NNT=8). The rate of clinical improvement was significantly greater in the aggressive IVF group.
Limitations: Although no patients in the study developed signs of fluid overload, patients at risk for volume overload were excluded, limiting external validity. The composite outcome has not been validated. Patients overall were relatively young and healthy. It’s a really small study; persistent SIRS developed in 2 vs. 7 patients.
Practice Changing? This is not a high enough quality study to be practice changing per Jenny. Jeff was more willing to follow the paper’s recommendations. However, studies on severe pancreatititis have demonstrated negative outcomes associated with aggressive IVF; third spacing, ARDS, renal failure, CHF, abdominal compartment syndrome: aggressive IVF treatment should be reserved for patients with mild pancreatitis.
Bottom line: Overall, the majority at JC felt aggressive IVF are appropriate for patients with mild pancreatitis, and do align with current American College of Gastroenterology recommendations for fluids in pancreatitis.