EPI 245 Assignment 1 – Identify a gap between evidence and practice: the problem statement.
I’m interested in the treatment of sepsis in resource-limited settings, like in sub-Saharan Africa. An interesting conundrum has recently been encountered with regards to the appropriate use of intravenous fluids for patients with sepsis. In well-resourced settings, it is widely accepted that early and aggressive administration of intravenous fluid is life-saving in patients with sepsis. This is thought to be because, in sepsis, leaky blood vessels lead to hypovolemia, distributive shock, and, ultimately, death; bolus resuscitation when sepsis is recognized helps to mitigate or even avert shock. Many randomized clinical trials in have established the benefit of early fluid resuscitation in the United States, Europe, and Australia.
Until recently, not much was known about fluid resuscitation practices for sepsis in sub-Saharan Africa. A few observational studies suggested that patients with sepsis received far less in fluids that they would have had they been treated in the United States. Then, in 2017, a study in Zambia published the results of a randomized clinical trial comparing an early fluid resuscitation strategy with usual care in patients with sepsis, and found, surprisingly, that patients who were treated with an early fluid resuscitation strategy had increased mortality compared to usual care.
The conundrum is this: why would early fluid resuscitation have a different effect on patients with sepsis in Africa than it would in the United States?
In some ways, this is not really a gap between evidence and practice; it’s a gap between evidence and evidence. But that gap is really rich, and there’s all kinds of hypotheses. To wit:
1. Is there a difference in the epidemiology of sepsis in the United States and in Africa? For example, does sepsis from tuberculous mycobacteremia—never seen in the US but makes up a sizable proportion of septic patients in sub-Saharan Africa—behave differently than conventional gram negative or gram positive sepsis?
2. Aggressive and early fluid resuscitation sometimes causes pulmonary edema and respiratory failure. In the US, respiratory failure is treated with invasive mechanical ventilation. In sub-Saharan Africa, invasive mechanical ventilation is unavailable, and respiratory failure has a very high mortality rate. Does the lack of invasive mechanical ventilation explain the difference in outcomes from early fluid resuscitation?
3. In the United States, septic patients are often admitted to the ICU with 1:2 or even 1:1 nursing ratios. In sub-Saharan Africa, access to ICU level care is frequently unavailable, and nursing ratios on the wards vary from 1:30 to 1:50. Does lack of access to ICU-level nursing ratios account for the difference in outcomes from early fluid resuscitation?
There are multiple avenues of inquiry—differences in access to emergency care, differences in insurance coverage (or lack thereof), differences in availability of diagnostic tests, differences in microbial epidemiology and resistance patterns, differences in availability of antibiotics, and differences in access to adjunctive therapies like renal replacement therapy, to name a few. The options are overwhelming, and one challenge is ascertaining which might be promising to investigate.