Crit Care Shock (2019) 22:214-221 Accuracy of calculated creatinine among amputees: case presentation and literature review Janay Bailey, Elizabeth Awudi, Charlene Kalani, George Udeani, Joseph Varon, Salim Surani Abstract sionals must judiciously review the patient ho- Dosing vancomycin for patients who do not fol- listically, practice evidence-based medicine, and low population pharmacokinetics can be chal- consider the overestimation of renal function, lenging. Standard predictive clinical equations when calculating doses for this and other do not account for extreme patient characteris- agents. While current literature does not pro- tics. In particular, serum creatinine is signifi- vide a clear consensus for this population, there cantly reduced while creatinine clearance is are several factors to take into consideration overestimated in patients with amputations. The when determining the optimal dose in patients “missing” body part must be accounted for presenting to the hospital requiring medications when executing a dosing regimen for these chal- dosed by changes in renal function. We recently lenging patients. In addition, health care profes- had one such case. . Key words : Creatinine, amputee, amputation, creatinine clearance, vancomycin, glomerular filtration rate, GFR. Introduction dosing interval strategies of conventional (multiple The accuracy of equations predicting creatinine daily dosing) or extended interval dosing (once clearance (CrCl) may be altered by several patient daily dosing), is chosen based on a patient’s CrCl factors, such as malnutrition, obesity, old age, un- and other factors. (3) Extended interval dosing stable renal function, amputations, spinal cord inju- must not be used in patients with renal insufficien- ry, and critically illness. (1) These special consid- cy. (3) In addition, actual body weight should be erations also determine if some medications should used unless the patient has obesity. (3) The latter be dosed based on actual body weight, ideal body may be defined as actual body weight greater than weight, or adjusted body weight. (2) Examples of 20% of ideal body weight, or a body mass index these medications include aminoglycosides, low- (BMI) of 30 or greater. (3) Obese patients should molecular-weight heparins (LMWH), acyclovir, be dosed only using adjusted body weight. (3,4) and vancomycin. (2) For example, aminoglycoside LMWH are dosed based on actual body weight, . and the dose should be decreased when renal func- tion is below 30 ml/min. (5) Acyclovir, on the oth- er hand, is dosed based on actual body weight, un- less the patient is obese, in which case ideal body weight should be used. Dosing concentration, as well as the interval, should also be modified ac- From Corpus Christi Medical Center, Corpus Christi, Texas, USA (Janay Bailey, Charlene Kalani), Bay Area Heart Hospi- cording to CrCl. tal, Texas, USA (Elizabeth Awudi), Texas A&M University, In general, CrCl makes a significant difference in Corpus Christi, Texas, USA (George Udeani, Salim Surani), the dosing interval of renally excreted medications, The University of Texas Health Science Center at Houston, therefore, it is imperative to measure this parame- United General Hospital, Houston, Texas, USA (Joseph Va- ter as accurately as possible. Due to variability, ron). drug concentrations may be monitored when con- sidered appropriate and useful. Goals of monitor- Address for correspondence : ing include preventing toxicity, evaluating effica- Salim Surani Texas A&M University, Corpus Christi, Texas, USA cy, and clinical management. (2) 214 Crit Care Shock 2019 Vol. 22 No. 4
Case presentation displayed mild to moderate mitral regurgitation A 56-year-old gentleman with a past medical histo- and mild tricuspid regurgitation on the color-flow ry of coronary artery disease, hypertension, atrial Doppler, but no evidence of endocarditis. Patient fibrillation, congestive heart failure, transient is- also had new complaints of upper thoracic spine chemic attack, myocardial infarction, chronic pain, area and a magnetic resonance imaging (MRI) tho- left leg amputation, and previous infection with racic-spine was ordered to rule out osteo/diskitis methicillin resistant Staphylococcus aureus due to tenderness. The scan revealed mild osseous (MRSA) of the left hip, presented to emergency edema within the T5 segment and disc bulge at department with a three-day onset of productive T11-12, but no convincing evidence of discitis. cough, chest pain, generalized fatigue, weakness, The patient then began complaining of left wrist fever, body aches, chills, nasal congestion, pain in pain, however, x-ray of the wrist was unremarka- his lower back and right lower extremity, and onset ble. After a few days, left wrist swelling improved. of shortness of breath. He also reported having After 14 days, the patient was clinically stable with multiple infected abscesses from orthopedic devic- no other acute events. An order for a new Gro- es for his left hip disarticulation amputation. The shong catheter placement was completed and the patient was a smoker for over 20 years and drank patient was discharged home on cefazolin for 4 5-6 beers daily. In the emergency department weeks of intravenous (IV) antibiotics. (ED), a chest computed tomography (CT), revealed moderate size consolidation in the right lower lobe Discussion with surrounding ground glass opacities in the Dosing in amputees can be challenging. In our right lower and middle lobes, and a small right case, two different creatinine clearance values pleural effusion ( Figure 1 ). Blood and sputum cul- were clinically significant enough to make a dif- tures were collected, ceftriaxone and azithromycin ference between every 8 versus 12-hour interval administered one time in the ED and a diagnosis of dosing. healthcare-associated pneumonia (HCAP) was Clinicians must consider the percentage of esti- made. Vancomycin 1500 mg every 12 hours was mated body weight lost (% EBWL) in patients with initiated empirically pending culture results and the amputations. These changes in therapy may have a Clinical Institute Withdrawal Assessment (CIWA) major impact on achieving therapeutic versus non- protocol was started. The patient’s body weight therapeutic concentrations, and influencing the was 90.7 kilograms, with a body mass index of probability of toxicity. 28.6 kg/m 2 . At the time vancomycin was initiated, For example, vancomycin remains one of the most the blood urea nitrogen (BUN) and serum creati- common antibiotics used in the United States for nine (SCr) were 13 mg/dl and 0.87 mg/dl respec- the treatment of infections caused by MRSA. (6) tively. Using the Cockcroft-Gault equation, his This glycopeptide exhibits slow bactericidal prop- estimated CrCl, based on regular ideal body erties by inhibiting cell wall synthesis. (7) The an- weight, was calculated to be 97.9 ml/min. Howev- tibiotic binds to the d-alanyl-d-alanine portion of er, when taking into account the patient’s estimated the bacterial cell wall and blocks peptidoglycan body weight loss due to his amputation, his esti- polymerization. (7) Some studies have shown van- mated CrCl was 84 ml/min. After three vancomy- comycin to display concentration-independent, cin doses, a trough level was obtained about an time-dependent pharmacokinetic-pharmacodyna- hour prior to the next scheduled dose, which re- mic (PK/PD) properties. (8) The area under the sulted in a level of 11 mcg/ml. Blood and sputum plasma concentration-time curve to minimum in- cultures and sensitivities revealed methicillin sen- hibitory concentration (AUC/MIC) ratio is recom- sitive Staphylococcus aureus (MSSA) and antibiot- mended as the preferred parameter to measure ics were de-escalated to cefazolin 2 grams every 8 vancomycin’s efficacy and prevent toxicity. (6,8) hours. His right Groshong catheter of 4 months Yet, despite the vast amount of research performed was removed with peripherally inserted central on this drug, controversies and conflicting evi- catheter (PICC) lines and catheter tip cultures and dence still remain. (6) These issues include serum sent to lab. Later a CT of the abdomen showed flu- concentration expected to reach toxicity, interpre- id collection with gas at the left hip which was then tation of laboratory parameters to measure effica- drained and sent to the lab. PICC line cultures cy, and the potential for nephrotoxicity and ototox- grew MSSA while catheter tip and body fluid cul- icity with different dosing concentrations. (9) Evi- tures did not isolate any organisms. Infectious dis- dence-based research in dosing vancomycin in eases and cardiology consult teams agreed to order obese and amputee patients is limited, however, a transthoracic echocardiogram (TEE), which dis- initially all populations are generally dosed using . . Crit Care Shock 2019 Vol. 22 No. 4 215
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