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Date: February 22nd, 2019

Reference: Lane et al. Association Between Early Intravenous Fluids Provided by Paramedics and Subsequent In-Hospital Mortality Among Patients With Sepsis. JAMA 2018

Guest Skeptics: Jay Loosley is the Superintendent of Education at Middlesex-London Paramedic Service. Jenn Doyle is a paramedic educator at Middlesex-London Paramedic Service.

Case: A 77-year-old man’s partner calls 911 because he has a fever, cough, shortness of breath and lethargy. The patient is known to have hypertension and dyslipidemia. Paramedics arrive quickly and find a man in bed with a temperature of 39.5C, heart rate of 111 beats per minute, respiratory rate of 24 breaths per minute, oxygen saturation of 91% and a blood pressure of 98/56. They suspect a respiratory infection, provided supplemental oxygen with a target of 94-96% (SGEM#243), establish IV access and begin a 500cc normal saline bolus.

Background: Sepsis is a serious condition with high morbidity and mortality. It has been covered on the SGEM many times over the last seven seasons (SGEM# 69, 90, 92, 113, and 168).

Recently we covered a paper looking at whether or not pre-hospital antibiotics could provide a benefit to patients with varying degrees of sepsis (SGEM #207).  The study by Alam et al took adult patients with a diagnosis of suspected infection and randomized them to ceftriaxone 2g IV started pre-hospital or usual care with a primary outcome of all-cause mortality at 28 days.

Jennifer Doyle

The bottom line from that episode pre-hospital antibiotics in the ambulance do not appear to have a mortality benefit in patients with varying degrees of sepsis in an optimized EMS system.

The Surviving Sepsis Campaign makes a number of recommendations in their 2016 guideline. One recommendation that they make is the rapid administration of 30ml/kg of crystalloid for hypotension. This is a strong recommendation from SSC based on low quality evidence. This was updated in 2018 with the 3-hour and 6-hour bundles combined into a single 1-hour bundle. This led to a petition requesting the SSC retract their 2018 guidelines (SGEM Xtra). For more information see PulmCrit recent post.

Clinical Question: Is IV fluid administration by Paramedics for patients with suspected sepsis associated with reduced in hospital mortality rates?

Reference: Lane et al. Association Between Early Intravenous Fluids Provided by Paramedics and Subsequent In-Hospital Mortality Among Patients With Sepsis. JAMA 2018

  • Population: Patients with sepsis identified using the international Statistical Classification of Disease and Related Health Problems, Tenth Revision (ICD-10CA) coding that was modified to be consistent with the Third International Consensus Definition for Sepsis and Septic Shock (Sepsis-3).
    • Patients were classified as having sepsis if all three of the following conditions were present: they received a diagnosis in the ED of infection, they were admitted to the hospital or died in the ED, and they had evidence of organ dysfunction.
    • Excluded: Patients discharged home or who left the ED without being treated
  • Exposure: IV fluids initiation and/or administration of any volume of crystalloid fluid by Paramedics either on scene or enroute to the ED for patients with suspected sepsis.
  • Comparison: Those patients with suspected sepsis who did not receive IV fluids by Paramedics.
  • Outcome:
    • Primary Outcome: In hospital mortality.
    • Secondary Outcomes: Total volume of IV fluids administered by Paramedics, total prehospital time interval, or the time to assessment by a physician after arrival at the hospital.

Authors’ Conclusions: “Intravenous fluids provided by paramedics were associated with reduced in-hospital mortality for patients with sepsis and hypotension but not for those with higher initial systolic blood pressure.”

Quality Checklist for Observational Study:

  1. Did the study address a clearly focused issue? Yes
  2. Did the authors use an appropriate method to answer their question? Yes/No
  3. Was the cohort recruited in an acceptable way? Yes
  4. Was the exposure accurately measured to minimize bias? Yes
  5. Was the outcome accurately measured to minimize bias? Yes
  6. Have the authors identified all-important confounding factors? Unsure
  7. Was the follow up of subjects complete enough? Yes
  8. How precise are the results? Fairly precise for the Odds Ratio of mortality.
  9. Do you believe the results? Yes
  10. Can the results be applied to the local population? No
  11. Do the results of this study fit with other available evidence? Yes

Key Results: There were close to 150,000 adult patients transported to the hospital by Paramedics during the study period. They identified 1,871 patients in the ED as having sepsis. The median age was 77 years. More than half (54%) received IV fluids, 8% having an IV placed and 38% received no IV fluids. The overall mortality rate was 28% (2% in the ED and 26% in the hospital).

Mortality was higher in patients with sepsis treated by paramedics with IV fluids (31.7%) vs. those with no IV fluid treatment (24.1%). 

  • Primary Outcome:In hospital mortality gets complicated when you adjust for hypotension and consider those who received IV boluses. Those patients who received any fluid and were hypotensive or received a bolus had a lower odds ratio (OR) of mortality. 

  • Secondary Outcomes:
    • Median total volume of IV fluids administered by Paramedics was 400ml
    • Patients who received IV fluids had longer prehospital times than patients not receiving intravenous fluids (median difference, 3.2 minutes; 95% CI, 1.7-4.7 minutes)
    • Administration of IV fluids was not associated with time to MD assessment (median difference, 2.4 minutes; 95% CI, –2.4 to 7.3 minutes)

  1. Diagnosis of Sepsis: The can be a difference between ED diagnosis of sepsis and Paramedic impression of sepsis. Paramedics screen patients for sepsis using SIRS criteria. The patients in this study were classified as having sepsis if all three conditions were present: they received a diagnosis in the ED of infection, they were admitted to the hospital or died in the ED, and they had evidence of organ dysfunction.
  2. Time to Physician Assessment: Patients who were hypotensive had a shorter time to physician assessment as they were deemed to be more critical and thus required more rapid treatment. As paramedics do not administer antibiotics on scene, a faster time to physician assessment is highly likely to be associated with more rapid antibiotic administration. However, as we discussed in SGEM #207, even pre-hospital antibiotics did not provide a mortality benefit.
  3. Right Amount of IV Fluids: The median volume of IV fluids was only 400ml. This might not be enough to provide a clinically important benefit. Guidelines have suggested 30ml/kg of IV crystalloid be given in patients with sepsis induced hypoperfusion. However, this IV fluid bolus recommendation from the Surviving Sepsis Campaign is based on low quality evidence. The honest answer is we do not know what the right about of IV fluids are needed in these patients.
  4. Missing Data: How researchers handle missing data is important. This study had missing data from 0% for some data points to as high as 36%. However, it depends on what data was missing and was it clinically relevant. The most common data missing (36%) was for the patient’s weight. Vital sign measurements were missing in <3% of patients. They then bootstrapped the data to see how well the data stood up.
  5. Controlling for Confounders: This was an observational study and represents the greatest limitation to the study. They attempted to control for any potential confounders. They also did propensity-matched analysis to match patients who received IV fluids to those who did not receive IV fluids. While this helps minimize some of the bias, it is not possible to control for all unmeasured confounders and these could be responsible for the results observed. To determine if pre-hospital IV fluids cause a reduction in mortality a properly designed randomized control trial would need to be conducted.

Comment on Authors’ Conclusion Compared to SGEM Conclusion: We agree that they demonstrated an association between pre-hospital IV fluids and in hospital mortality in patients with sepsis.

SGEM Bottom Line: In patients suspected of sepsis, we don’t know if pre-hospital IV fluids will result in a patient-oriented benefit.

Case Resolution: The patient arrives at the ED with a temperature of 37.9C, HR 98bpm, RR 20bmp, SpO2 95% with 2L nasal prongs and a blood pressure of 106/70. You relay you suspicions of sepsis secondary to pneumonia and the ED staff start working up the patient.

Jay Loosley

Clinical Application: Paramedics have different medical directives in different jurisdictions. In Ontario, there is no standing medical direction for IV fluid administration for septic patients. This represents a barrier for implementing such a protocol in our EMS system. This patient was hypotensive and there are protocols for providing IV fluid boluses in these cases.

What Do I Tell My Patient? We think you have an infection in your lungs causing a fever and your blood pressure to be low. We are going to start and IV and give you some fluids.  I will going to call ahead to the hospital to let them know we are coming, and by this IV already being in place, it will speed up your care.

Keener Kontest: Last weeks’ winner was Rovi Origenes a Nurse Practitioner from Illinois. They knew the three types of rental detachments are:

  • Rhegmatogenous – The underlying fluid lifts retina up (most common) myopia related.
  • Exudative – Fluid from the retinal vessels from vasculitis, papilledema, and hypertension.
  • Tractional – Diabetic retinopathy, SS disease, vitreous hemorrhage (fibrous bands) pull it off.

Listen to the SGEM podcast to hear this the new keener question. If you know the answer send an email to TheSGEM@gmail.com with “keener” in the subject line. The first correct answer will receive a cool skeptical prize.

Remember to be skeptical of anything you learn, even if you heard it on the Skeptics’ Guide to Emergency Medicine.

Jenn Doyle & Jay Loosley