Tag Archives: infection

Best of EAST #2: Blood Transfusion And Nosocomial Infection

This abstract falls into the “interesting, but how can we use this bit of information” category. We’ve known that transfusing packed red cells raises nosocomial infection rates for at least 15 years. The group led by MetroHealth in Cleveland combined forces with the Vanderbilt trauma group to re-look at their data from the PAMPer trial with respect to trauma patients.

The PAMPer trial (Prehospital Air Medical Plasma) examined the effect of tranfusion of two units of plasma in the air ambulance on mortality, transfusion need, and complications. Half of the patients got plasma plus standard care, and the other half standard care alone.

This abstract uses PAMPer trial data to examine the impact of giving any amount of blood on nosocomial infection in these patients. These infections included pneumonia, bloodstream infection, C Diff colitis, empyema, and complex intra-abdominal infection.

The group retrospectively analyzed the prospectively collected PAMPer data and used logistic regression models to test for an association.

Here are the factoids:

  • A total of 399 patients with the usual trauma demographics were included (younger male, moderately injured, blunt mechanism)
  • Ten percent of patients died, and 23% developed nosocomial infections
  • Pneumonia was by far the most common complication (n=67) with all others in the low teens or below
  • Although only two thirds of patients received plasma, 80% were given PRBCs and 27% received platelets
  • Patients who received any amount of packed cells had a 2.3x increase in nosocomial infections, and the number given increased the rate of nosocomial infection (1.06x)

The authors concluded that patients in the PAMPer trial who received at least one unit of blood “incurred a two-fold increased risk of nosocomial infection” and that this risk was dose dependent.

My analysis: The biggest obstacle for me to buy into this work is the enrolled patient group. Studies in which you borrow someone else’s data are always a bit problematic. You have no control over the variables, as they’ve been determined by someone else.

In this case, the dataset could only be controlled for age, sex, and ISS. But what about all the other stuff that might have an impact on infections? Things like pulmonary injury, the 20% of patients who had penetrating injury, and severe TBI patients with their propensity to develop VAP.

The odds ratios of the associations were a bit on the low side. Sure, the overall nosocomial infection odds ratio was 2.37 but the confidence interval was 1.14 to 4.94. This is very wide and it means that the odds could have been anywhere from 1.14x to almost 5x. This suggests that the study group may not have been large enough to give us a clear picture. And the odds ratio for number of PRBC units vs infection was only 1.06 with a tighter confidence interval. So even if it is present, this association is very, very weak. I like to see ridiculously large odds ratios when reviewing observational studies like this where the input data is constrained.

My final comment on this study deals with its utility. These are trauma patients. They are bleeding. We’ve known that transfusions may increase the nosocomial infection rate in critically ill patients for at least 15 years. But we will still have to give the patients blood. So what are we to do?

Here are some questions for the authors and presenter:

  • Please comment on the limitations you faced using the PAMPer dataset. Were you satisfied with the range of variables available? Which additional ones would you have liked to work with?
  • Do you feel that the 399 patients provided enough statistical power for analysis? The confidence intervals are large and very close to the OR=1 line.
  • What should we do with your conclusions? Can we translate this into clinical practice?

One final note: the patients did not “incur increased risk.” Rather, there was an association with increased risk of infection. We really don’t know if it was from the blood or something else that was not recorded in the PAMPer dataset.

Reference: Dose-dependent association between blood transfusion and nosocomial infections in trauma patients: a secondary analysis of patients from the PAMPer trial. EAST 2021, Paper 3.

Whaaat? Stuff You Sterilize Other Stuff With May Not Be Sterile??

When one works in the trauma field, or medicine in general, we deal with the need for sterility all the time. We use equipment and devices that are sterile, and we administer drugs and fluids that are sterile. In surgery, we create sterile fields in which to use this sterile stuff.

In the past few years, we’ve come to the realization that the sterility we take for granted may not always be the case. There have been several cases of contaminated implanted hardware. And a few years ago, supposedly sterile injectable steroids were found to be contaminated with fungus, leading to several fatal cases of meningitis.

An article in the New England Journal of Medicine brings a bizarre problem to light: microbial stowaways in the topical products we use to sterilize things. Most drugs and infused fluids are prepared under sterile conditions. However, due to the antimicrobial activity of topical antiseptics, there is no requirement in the US that they be prepared in this way.

A number of cases of contamination have been reported over the years:

  • Iodophor – contamination with Buckholderia and Pseudomonas occurred during manufacture, leading to dialysis catheter infection and peritonitis
  • Chlorhexidine – contaminated with Serratia, Buckholderia and Ralstonia by end users, leading to wound infections, catheter infections, and death
  • Benzalkonium chloride – contaminated with Buckholderia and Mycobacteria by end users, causing septic arthritis and injection site infections

Bottom line: Nothing is sacred! This problem is scarier than you think, because our most basic assumptions about these products makes it nearly impossible for us to consider them when tracking down infection sources. Furthermore, they are so uncommon that they frequently may go undetected. The one telltale sign is the presence of infection from weird bacteria. If you encounter these bugs, consider this uncommon cause. Regulatory agencies need to get on this and mandate better manufacturing practices for topical antiseptics.

Reference: Microbial stowaways in topical antiseptic products. NEJM 367:2170-2173, Dec 6 2012.

Best Of EAST #7: Is There A Relationship Between Number Of Transfusions And Infection?

It has long been known that blood transfusion decreases immunocompetency for a period of time. This has been taken advantage of in transplant surgery for decades. And blood transfusions are used liberally in major trauma. So could blood transfusion make it more likely for a trauma patient to suffer complications such as pneumonia, sepsis, and surgical site infections?

The group at the Massachusetts General Hospital explored this possibility. The analyzed four years of TQIP data, examining patients who received blood transfusions within four hours of arrival. They excluded transfers in, patients with incomplete transfusion counts, and those who died within 48 hours.

They focused on pneumonia, sepsis, and surgical site infections and statistically controlled for demographics, comorbidities, injury severity, and surgical/procedural interventions.

Here are the factoids:

  • A million patients (!) were reviewed and about 41,000 met study criteria
  • The odds ratio of infectious complications increased from 1.23 after 2 units to 4.89 after 40 units
  • Each additional unit after 40 increased the odds of an infection by another 4.9%

The authors concluded that blood transfusion is associated with a dose dependent risk of infectious complications and that patients should be resuscitated to achieve prompt hemorrhage control (really?).

My comment: Well, this certainly looks fairly straightforward. Of course, it suffers from the usual drawbacks of massaging large databases. And remember, it shows an association, not cause and effect. How can we tease out whether the higher infection risk is due to badly hurt patients who need major surgery and prolonged ICU stays with pneumonia? The authors have tried to reduce this as much as possible using logistic regression. Unfortunately, many of the variables are very interdependent and I don’t believe the methods can fully overcome this. And there may be other factors not available for analysis in the TQIP data.

Here is my only question for the authors and presenter:

    • How can you be sure that you have fully controlled for the key variables that might influence your final analysis? Yes, you considered demographics, three listed comorbidities (cirrhosis, diabetes, and steroid use), injury severity, and some interventions. But might there be other factors not listed and maybe not even in the TQIP data? Ideas?

This is one of those papers that makes you say “hmm”. But don’t we always try to stop the bleeding promptly. I’m not sure what alternative we have to giving blood.

Reference: Overtransfusion comes at a significant cost: the dose-dependent relationship between blood transfusions and infections after major trauma. EAST Annual Assembly abstract #26, 2020.

Stuff You Sterilize Other Stuff With May Not Be Sterile??

When one works in the trauma field, or medicine in general, we deal with the need for sterility all the time. We use equipment and devices that are sterile, and we administer drugs and fluids that are sterile. In surgery, we create sterile fields in which to use this sterile stuff.

In the past few years, we’ve come to the realization that the sterility we take for granted may not always be the case. There have been several cases of contaminated implanted hardware. And a few years ago, supposedly sterile injectable steroids were found to be contaminated with fungus, leading to several fatal cases of meningitis.

An article in the New England Journal of Medicine brings a bizarre problem to light: microbial stowaways in the topical products we use to sterilize things. Most drugs and infused fluids are prepared under sterile conditions. However, due to the antimicrobial activity of topical antiseptics, there is no requirement in the US that they be prepared in this way.

A number of cases of contamination have been reported over the years:

  • Iodophor – contamination with Buckholderia and Pseudomonas occurred during manufacture, leading to dialysis catheter infection and peritonitis
  • Chlorhexidine – contaminated with Serratia, Buckholderia and Ralstonia by end users, leading to wound infections, catheter infections, and death
  • Benzalkonium chloride – contaminated with Buckholderia and Mycobacteria by end users, causing septic arthritis and injection site infections

Bottom line: Nothing is sacred! This problem is scarier than you think, because our most basic assumptions about these products makes it nearly impossible for us to consider them when tracking down infection sources. Furthermore, they are so uncommon that they frequently may go undetected. The one telltale sign is the presence of infection from weird bacteria. If you encounter these bugs, consider this uncommon cause. Regulatory agencies need to get on this and mandate better manufacturing practices for topical antiseptics.

Reference: Microbial stowaways in topical antiseptic products. NEJM 367:2170-2173, Dec 6 2012.

Stuff You Sterilize Other Stuff With May Not Be Sterile??

When one works in the trauma field, or medicine in general, we deal with the need for sterility all the time. We use equipment and devices that are sterile, and we administer drugs and fluids that are sterile. In surgery, we create sterile fields in which to use this sterile stuff.

In the past few years, we’ve come to the realization that the sterility we take for granted may not always be the case. There have been several cases of contaminated implanted hardware. And most recently, supposedly sterile injectable steroids were found to be contaminated with fungus, leading to several fatal cases of meningitis.

A recent article in the New England Journal of Medicine brings a bizarre problem to light: microbial stowaways in the topical products we use to sterilize things. Most drugs and infused fluids are prepared under sterile conditions. However, due to the antimicrobial activity of topical antiseptics, there is no requirement in the US that they be prepared in this way.

A number of cases of contamination have been reported over the years:

  • Iodophor – contamination with Buckholderia and Pseudomonas occurred during manufacture, leading to dialysis catheter infection and peritonitis
  • Chlorhexidine – contaminated with Serratia, Buckholderia and Ralstonia by end users, leading to wound infections, catheter infections, and death
  • Benzalkonium chloride – contaminated with Buckholderia and Mycobacteria by end users, causing septic arthritis and injection site infections

Bottom line: Nothing is sacred! This problem is scarier than you think, because our most basic assumptions about these products makes it nearly impossible for us to consider them when tracking down infection sources. Furthermore, they are so uncommon that they frequently may go undetected. The one telltale sign is the presence of infection from weird bacteria. If you encounter these bugs, consider this uncommon cause. Regulatory agencies need to get on this and mandate better manufacturing practices for topical antiseptics.

Reference: Microbial stowaways in topical antiseptic products. NEJM 367:2170-2173, Dec 6 2012.