I-FiBH Trial: Intravenous Fluids in Benign Headaches – A Randomised, Single-Blinded Clinical Trial

Background:  Headache was the 5th most common reason for patients to present to the emergency department in the US in 2016.  Often ED providers include IV fluid boluses in their headache treatment cocktail, with prior research demonstrating IV fluids are included approximately 40% of the time (Jones).  While dehydration may precipitate some headaches, there is little evidence to support the use of IV fluids for their treatment.

Article:  Zitek T et al. I-FiBH Trial: Intravenous Fluids in Benign Headaches – A Randomised, Single-Blinded Clinical Trial. Emerg Med J. 2020. PMID: 32620543.

Clinical Question: In patients presenting to the emergency department for  a benign headache, do IV fluids help reduce pain or improve outcomes? 

What They Did:

• Single-centre, single-blinded, randomised controlled trial of patients presenting to the ED with a chief complaint of headache at a single center in Las Vegas, NV
• Convenience sample of patients based on the availability of research assistants who were knowledgeable of the study protocol. Research assistants were generally in the ED from 14:00 to 22:00. 
• All patients received the same standardized medications:
  • Diphenhydramine 1 mg/kg up to 50 mg intravenous, followed by
  • Prochlorperazine 0.15 mg/kg up to 10 mg intravenous 
• Patients received IV fluids per randomization to either intervention or control group. IV fluids were given using a pump that was covered with an opaque sheet to blind both the patient and the research assistant to the amount of fluid being given.
• Treating physician and nurse were not blinded
• Physicians were given instructions to hold any rescue medications for at least 30 minutes.

Intervention: 

• Fluid bolus group received 20 mL/kg up to 1000 mL of normal saline over 1 hour 

Control:

• Control group received normal saline at 5 mL/hour. 

Outcomes:  

• Primary Outcome: Difference in mean pain score at 60 min
• Secondary Outcomes:
  • Differences between the groups with regards to improvements in pain scores at 30 min and improvements in nausea scores at 30 and 60 min
  • Rates of vomiting
  • Rates of rescue medications
  • Rates of admission
  • Rates of headache resolution 24-48 hours after treatment

Inclusion:  Patients were eligible for inclusion if they presented to the ED with: 

• Chief complaint of headache,
• Between 10 and 65 years old and 
• Had a normal neurological examination

Exclusion:  Patients were excluded if they 

• Were pregnant 
• Had meningeal signs
• Had a fever
• Had suspected acute angle closure glaucoma
• Had head trauma or a lumbar puncture within the previous 2 weeks
• Had a thunderclap onset of their headache
• Had a known allergy to one of their study drugs 
• Had a history of intracranial hypertension
• Were a prisoner 
• Were non-English speaking (or had a non-English speaking guardian, if pediatric) 
• Had received analgesics or intravenous fluids prior to enrollment or were deemed to have severe dehydration (as determined by the treating physician’s history and physical exam) 

Results:

• Patients were enrolled between May 2017 and February 2019.  One study investigator left during recruitment at which data collection was being performed and study enrollment was discontinued prior to the target enrollment of 90 patients

• • • 67 patients screened
    • 58 patients enrolled
      • 35 randomized to bolus group
        • Two patient in this group did not want to stay for entire treatment course and withdrew from study
      • 23 randomized to control group
    • 56 patients in final analysis
  • Age range 10 – 65 years (median 29.5)
  • 63.8% female

• Primary Outcome:
• • Bolus Group: Mean drop in pain score of 48.3 mm
  • Control Group: Mean drop in pain score of 48.7 mm
  • 0.4 mm difference between the groups was not statistically or clinically significant
    • Prior research of Visual Analog Scale (VAS) found that a clinically significant change is represented by a 13 mm change   
• A sensitivity analysis was performed assuming the two patients who withdrew from the study did so because their pain was completely resolved.  With this assumption, the difference between the groups increased to 0.7 mm, but was still neither statistically nor clinically significant
• There were no statistically significant differences for any of the secondary outcomes

Strengths:

• Clinically relevant question
• Previous studies also small, so this adds to an existing body of literature in a useful way 
• No patients randomized to the control group received a fluid bolus
• All patients in the fluid bolus group received the full fluid bolus with the exception of two patients who withdrew from the study early (each of them received about 1/2 the fluid bolus)
  • Analysis was performed to account for these patients withdrawing from the study
• No statistically significant differences between groups in terms of initial mean pain score
• Although small, this is the largest RCT about IV fluid boluses for headaches to date

Limitations:

• Very small study size at a single institution
• Convenience sample of patients raises concern for selection bias which would limit the results generalizability
• Physicians and nurses were not blinded
• Enrollment was discontinued early and as a result the randomization resulted in uneven group numbers.  Because of this a small beneficial effect to the IV fluid bolus group may not have been detectable in this study
• A dopamine antagonist and antihistamine medication were given alongside the IV fluids for control.  There remains a possibility that IV fluids used in conjunction with an alternative medication class would be effective 

Discussion: This underpowered study in and of itself may not be practice changing, however, when taken along with the prior similar studies, it seems to show there is no benefit to IV fluids  In fact, this study, along with the prior studies, showed there was actually less pain reduction in IV fluid bolus group, albeit not statistically or clinically significant. While we usually don’t think a single liter of fluids can do much harm, unless given to a patient with volume overload, this study actually showed a trend toward worse outcomes in the IV fluid group.  Again these were not statistically significant, but patients in the bolus group received more rescue medications, were more likely to be admitted and more likely to have a headache at 24-48 hour follow up than those in the control group.  Furthermore, it is important  for us to consider both cost and flow considerations when considering treatment options for our patients.  According to a NY Times article from 2013, the manufacturer cost of a single liter of normal saline ranged from $0.44 – $1, but the cost to patients is significantly higher, with patient charges ranging from $500-700 for a single liter.  In an era of heightened awareness of cost conscious care as well as the significant financial burden of health care costs on our patients, we should avoid a more costly treatment without significant benefit.  Lastly, in an era of persistent ED boarding and long lengths of stay, we should consider the nursing effort and time involved in the delivery of a saline bolus.

Author’s Conclusion: “Though our study lacked statistical power to detect small but clinically significant differences, ED patients who received an intravenous fluid bolus for their headache had similar improvements in pain and other outcomes compared with those who did not.”

Clinical Take Home Point: In the absence of historical or clinical dehydration, there is little evidence to support the routine use of IV fluids for the treatment of benign headaches in the ED.

For More Thoughts on This Topic Checkout:

• Journal Feed: Does IV Fluid Help Treat Headache?

References:

1. Zitek T et al. I-FiBH Trial: Intravenous Fluids in Benign Headaches – A Randomised, Single-Blinded Clinical Trial. Emerg Med J. 2020. PMID: 32620543.
2. Jones CW et al. Epidemiology of Intravenous Fluid use for Headache Treatment: Findings from the National Hospital Ambulatory Medical Care Survey. Am J Emerg Med. 2017. PMID: 28233646.
3. National Hospital Ambulatory Medical Care Survey: 2016 Emergency Department Summary Tables. Accessed 2 Dec 2020. [Link is HERE]

Post Peer Reviewed By: Salim R. Rezaie, MD (Twitter: @srrezaie)

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