Page 69 - JSOM Fall 2025

Current antibiotic dosing practices for wound prophylaxis which may be used in resource-limited settings. The ex vivo
and infections are based on studies in non-hemorrhaging pa- IOCS assessment observed that 2% (SD 1%) of antibiotic in-
tients in civilian settings. These are frequently based on dosing oculated in whole blood was recovered in the IOCS reinfusion
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in healthy volunteers as part of pharmacokinetic analyses re- bag, whereas 97% (SD 17%) was found in the waste. These
quired for Food & Drug Administration approval. The limited observations were corroborated by results from two patients
available data for medication dosing in the cases of volume loss undergoing liver transplantation, in which only 2% of antibiot-
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and volume restoration primarily come from studies focused ics were recovered. Overall, their study concluded that there
on hemodialysis, plasmapheresis, and exchange transfusions, was a significant loss (95%) of antibiotics in blood when pro-
which have limited applicability to traumatic hemorrhage cessed through an autologous blood transfusion system and in
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and are more controlled, preplanned events. Data suggests vivo. This study emphasizes the need for studies on the effect of
that antibiotic dosing should be adjusted based on renal and transfusions on antibiotic and other drug concentrations.
liver function, particularly for elderly patients and those with
chronic kidney disease. 11–14 This information is rarely available Similarly, Markantonis et al. conducted an investigation in
in real-time during the initial resuscitation period. Unfortu- which the gentamicin concentration in serum and tissues was
nately, data on massive hemorrhage are very limited, despite measured with blood loss during colorectal surgery. Blood
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robust data on dose-reducing practices in the setting of re- and tissue samples were collected at specific times through-
duced kidney function. out each procedure. They found that many factors, such as
creatinine clearance, fluid administration, and blood loss,
A substantial amount of literature evaluates antimicrobial contributed to a loss of antibiotic concentration in serum and
dosing in cases of kidney replacement therapy (KRT) or hemo- tissue samples that did not meet the minimum inhibitory con-
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dialysis. 15,16 Antibiotic underdosing is common in KRT and he- centration required for adequate treatment. Swoboda et al.
modialysis due to increased volume of distribution and rapid measured the effect of intraoperative blood loss on prophylac-
removal, especially for low-protein-binding antibiotics. 17–26 tic cefazolin and gentamicin serum and tissue concentrations,
Based on these data, we can speculate that significant blood and similar results were observed. A correlation between
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loss could affect antibiotic dosing in a similar way. However, blood loss and decreased tissue antibiotic concentrations for
the physiological changes that occur during KRT or hemo- cefazolin (r=.73, P=.04) and the clearance of gentamicin from
dialysis differ from hemorrhage, as these treatments do not the tissues correlated with blood loss (r=.82, P=.01) was ob-
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rapidly remove fluid from the body in a whole blood volume– served. The results of these studies show how fluid loss and
loss manner. Moreover, their removal and potential replace- transfusion in the setting of hemorrhage will affect antibiotic
ment volumes are predictable and known in advance. In the concentrations. Additionally, it was concluded that the initial
setting of massive hemorrhage, blood replacement is complex, prophylaxis dose of 2mg/kg was insufficient for treatment and
as fluid rapidly redistributes across compartments from the recommended a higher dosage of 6mg/kg to account for the
interstitial space into the vasculature to replenish the volume antibiotic concentration decrement.
loss. The blood loss to blood volume replacement is often
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subjected to mismatches due to the desire to achieve permis- A recently published study discussed the importance of antibi-
sive hypotension and few methods to assess ongoing transfu- otic prophylaxis during cesarean deliveries. Fay and Yee point
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sion requirements. This further complicates physiology when out that the effectiveness of preoperative antibiotic doses can
compared to KRT or hemodialysis. Importantly, hemodialysis potentially be compromised by significant blood loss during
is often used specifically for drug removal in cases of toxic delivery. They emphasize the importance of redosing antibi-
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ingestions. Though there is less literature on plasmapheresis, otics to ensure proper levels in the bloodstream and tissues.
it is important to understand dosing in the setting of plasma- This is especially critical considering the rising rates of post-
pheresis due to its physiological resemblance to blood volume partum hemorrhage and the unique pharmacokinetics during
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loss. The process of plasmapheresis mirrors the effects of pregnancy. Low antibiotic concentrations in plasma can result
massive transfusion, where plasma and other blood compo- in insufficient antibiotic distribution in tissues. This is particu-
nents are lost and replaced, though this occurs in a predictable larly detrimental in cases of devitalized tissues, where signifi-
and planned fashion. However, during massive transfusions, cant antibiotic concentrations are needed to achieve effective
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all components are turned over, including the proteins that of- therapeutic levels. Although there is some literature on the
ten bind to antibiotics. There are limited studies focused on the pharmacokinetics of antibiotics in perioperative settings and
effects of plasmapheresis and antibiotics, which highlights the non-hemorrhaging patients, the pharmacokinetics of antibiotic
need for hemorrhage-specific data. 30–36 Moreover, alterations concentrations and transfusions in trauma patients is under-
in liver function occur as a result of ischemia. studied. To our knowledge, there is no literature specifically
researching the effects of massive transfusions and how they
In intraoperative settings for non-trauma patients, changes alter the pharmacokinetics in hemorrhagic patients, potentially
in antibiotic concentrations may occur due to blood loss and risking inadequate concentrations for tissue penetration. 41
transfusion. Lasko et al. measured the loss of four commonly
used antibiotics—vancomycin, piperacillin, ampicillin, and ce- We hypothesize that the drug plasma concentrations decrease
fazolin—in an ex vivo intraoperative cell salvage (IOCS) and with a direct relationship to the amount of blood transfused
in two patients undergoing liver transplantation. In IOCS, the during resuscitation after trauma. We seek to understand the
plasma and waste in blood lost during a surgical procedure are relationship between antibiotic concentrations and blood prod-
washed, and the red blood cells are reinfused to the patient. uct administration in the setting of hemorrhage. Our study has
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The use of Cell Saver (Haemonetics, Boston, MA) technology three proposed aims:
has limited applicability to the trauma setting as it requires spe-
cific machines that wash the red blood cells prior to reinfusion 1. Determine the plasma drug concentration at regular intervals
and does not mirror a true unprocessed autologous transfusion, during the first 12–18 hours after antibiotic administration.

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