This chapter deals with the management of sepsis in somebody without an immune system. The bone marrow transplant recipient is a good model of such a situation. Question 11 from the first paper of 2014 uses the bone marrow transplant as a backdrop for some sort of infectious-asounding diarrhoea.
The four stages of bone marrow transplantation
There are 4 well recognised risk periods in the population of BMT recipients. They follow a predictable time pattern. This is a timetable of the most common infectious complications one encounters on their road to new bone marrow.
Pathogens in the immunocompromised host
An immunocompetent host typically suffers sepsis at the hands of known, familiar enemies:
- E. coli
- Pseudomonas aeruginosa
An immunocompromised neutropenic host has much more to offer to a bacterium with ambition. There is a list of organisms which one needs to consider in addition to the above.
The CICM exam candidate should be able to not only regurgitate these, but produce some sort of rationale as to why they are being ordered.
The neutropenic broadside: empiric therapy for fever of unknown origin
This is not a recipe, but rather a list of options.
It is of course possible to unitelligently give all the antibiotics.
More skill is required to determine which are the appropriate ones.
The Sanford Guide, in its recommendations regarding the high-risk neutropenic patient, suggests the following cocktail:
- Meropenem or Cefepime
- an echinocandin (eg. Caspofungin)
- Voriconazole if fever persists and the patient has had a good amount of anti-candida prophylaxis.
If CNS involvement is suspected:
- Vancomycin -to cover beta-lactam resistant gram-positives
- Ampicillin - to cover Listeria
- Ceftriaxone - to cover Strep pneumoniae
- Amphotericin - to cover Cryptococcus
- Trimethoprim/sulfamethoxazole - to cover P.jirovecii
If diarrhoea is present
- Metronidazole-to cover C.difficile
NIV instead of intubation
A good NEJM article has suggested that intermittent NIV for these people is a better option than intubation, or standard high flow oxygen via Venturi mask. Specifically, the group randomised to NIV were less likely to die in the ICU. The inclusion criteria in this study were a respiratory rate of over 30, evidence of pulmonary infiltrates, fever and the deterioration of gas exchange beyond a PaO2/FiO2 ratio of 200. The use of NIV very early in these patients (i.e. as soon as they met these criteria) was associated with a massive decrease in the in-ICU death rate (from 69% to 38%). Indeed the only deaths that occurred were in the patients who progressed to intubation; and the incidence of sinusitis and pneumonia were higher in the group who did not receive NIV.
Some might argue that the patients who ended up intubated had a more severe pulmonary sepsis and this skews the data. Perhaps that is true. But everyone who got VAP died in this study. Other data has demonstrated that the advantage of NIV in patients with respiratory failure rests on the decrease in the incidence of VAP. Ergo, to avoid VAP is to avoid a significant proportion of ICU mortality in the immunocompromised population.
Shall we admit this person to the ICU?
The evidence demonstrates that ICU doctors and haem/onc doctors frequently disagree as to who belongs in the ICU and who doesn’t. One specific study has asked us to broaden our admission policy, given that only 78.7% of the BMT patients we consider “too well” to benefit from ICU will survive at 30 days. There appears to be good reason to err on the side of caution; common sense suggests that some of these people will benefit from 1:1 nursing and regular intensivist attention and thus may survive longer; other will be palliated in a more controlled environment, and will suffer less in their final hours.
The family conference
The prognosis is grim; that much is clear at even the resident level. But let us take a closer look at the data. The same study that suggested we admit more people has demonstrated that BMT patients we actually subject to ICU did even worse than the patients whom we judge to be “to well”; of these people only 54.2% survive at 30 days. Another study summarises the findings of many reports, and comes up with a figure of 65% for 30-day mortality, in ICU or after discharge from it. The allogenic patients tend to do poorly at 100 days (5-10% survival) in comparison to autologous transplant recipients. Additionally, it seems multi-organ system failure in this group is associated with a 100% in-ICU mortality. In a meta-analysis of 2653 patients, the strongest independent predictors for 1-year mortality were mechanical ventilation and hemodialysis. In a study by Soubani et al, nobody with an admission lactate over 6 had survived.