1. “Fever” in the SICU and IMC is 38.5° C or greater;
2. In the Burn ICU, because of the hypermetabolic state, fever is 39.3° C or greater (see below). 3. While the workup of fever is relatively complex, if infection is considered, the following should be
remembered:
i. For an initial culture evaluation of a fever, occurring more than 24 hours after a surgical procedure, Two (2) to sets of blood cultures, one urine specimen for culture and a sputum specimen should be obtained.
ii. If there are pulmonary infiltrates and / or if the patient has been mechanically ventilated for more than two (2) to three (3) days, a deep sputum specimen or brochoscopically directed sputum specimen is obtained. Send for Gram stain and non-quantitative cultures.
iii. A CBC with manual differential count (looking for elevated Band forms) should be obtained. iv. Consideration should be given, depending upon the time post-operatively and the surgical site, of
a surgical site infection / abscess.
v. If the patient spikes again within 24 hours, you generally need not repeat cultures. If greater than or equal to 24 hours, repeat the blood cultures (2 sets);
vi. The sputum and urine specimens need not be resent for culture any more frequently than every 48 to 72 hours, generally speaking.
4. With the Fellow / attending, and with the assistance of our Critical Care Clinical Pharmacy colleagues, in the setting where infection is considered likely, initiate antimicrobial therapy. Drugs should be chosen based upon the most likely site of infection and organism.
5. Common initial antimicrobial choices include:
i. Pneumonia / VAP: cefepime, vancomycin, fluconazole ii. Sepsis: cefepime, vancomycin, fluconazole
iii. If an intra-abdominal process is considered, the utilization of metronidazole ought be considered. iv. Because of a suspected risk for antibiotic-induced, Clostridium difficile related colitis, we prefer
not to use Clindamycin in our units.
6. Cultures and sensitivities are to be checked at least daily and reported to the Fellow / attending on rounds. The importance of up-to-date culture and sensitivity data cannot be
overemphasized.
7. Once sensitivities are obtained from the laboratory, antibiotics must be altered after discussion with the attending / Fellow / ICU Pharmacist
8. Stop dates for the antimicrobials should be written at the time the drugs are begun:
i. Pneumonia / VAP: 5 to 8 days of IV drugs (non-Pseudomonal / Acinetobacter, in these cases, 10 to 14 days)
ii. Recurrent VAP, Sepsis / Septic Shock: 10 to 14 days of IV drugs 9. Communicate decisions and concerns with the surgical service.
B. Fever Workup in the Burn Unit
1. Patients with burn injury are hyperthermic as a result of the burn and have a shift in their
thermoregulatory set point. As a result, a temperature of ≥ 39.2 C is considered the threshold for a fever workup instead of the standard 38.5 C. Patients immediately post-op may be febrile from seeding during debridement and typically do not warrant extensive workup.
2. Fever workup in any of our patients – Burned or not – includes the following:
a. Look at the patient and perform physical exam with emphasis on the following areas: i. Wounds: wound infection or cellulitis
ii. Lungs: Rhonchi or decreased breath sounds suggestive of secretions and consolidation
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iv. Extremities: look for evidence of DVT – warmth and swelling, particularly asymmetric v. Central lines, arterial lines, peripheral IVs for evidence of infection
b. CBC with manual diff (manual diff must be explicitly ordered) c. Chest x-ray
d. Urinalysis, urine culture (Not needed if done in past 72 hours unless urine looks dirty) e. Blood cultures – 2 sets of peripheral draws (Femoral vein stick if unable to obtain
peripherals). Please DO NOT culture through lines as this typically does not add useful data.
If the peripheral cultures are positive, the line will likely need to be removed.
f. If pneumonia is suspected, obtain a bronchoscopically guided deep sputum specimen or a BAL. Newly admitted patients undergoing bronchoscopy for assessment of inhalation injury do not need BAL.
3. Indications for empiric antibiotics
a. Hypotension or organ failure / dysfunction - Start Vanc / Cefepime and Cipro or Aminoglycoside
b. Evidence of wound infection / cellulitis – Start Kefzol if less than Post-Burn Day (PBD) 3, Vanc if PBD 3 or greater.
c. Positive UA – Start TMP/SMX or Cefazolin. Levofloxacin if later than PBD 14 d. High suspicion of pneumonia – Start Vanc and Cefepime
e. Add fluconazole if intra-abdominal infection or yeast suspected
Antibiotics should be tailored (narrowed down as much as possible) as soon as cultures are back, and no later than 72 hours
4. ANTIBIOTICS
Typical drugs, indications and dosages in patients without renal failure include:
Drug Indication Dosage Route
Vancomycin Staph and some 1 g bid IV
strep infections
Penicillin Clostridial infections 4 million units q4h IV
Flagyl Anaerobic infections 500 mg q6h IV
Cefepime Broad coverage 1 g q12h IV
Imipenem Broad coverage 500 mg q6h IV
and specifically pancreatitis
Tobramycin Pseudomonal and 7 mg/kg q24h IV
gentamycin infections
10 hr drug levels should be tested to determine that appropriate dosage interval has been given.
Drug Indication Dosage Route
Amikacin Broad coverage 5 mg/kg qd IV
particularly in face of resistance to other antibiotics
Diflucan Antifungal 400 mg qd NG pref
Ciprofloxacin Some gram negative 400 mg bid IV
coverage
A. PULSE-DOSE AMINOGLYCOSIDES
Dose = 7 mg / kg for gentamycin & Tobramycin Dosing Wt = IBW:
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Male = 50 kg – 2.3 (inches over 60) Female = 45 kg – 2.3 (inches over 60) if pt > 20% over IBW, add 0.4 (actual wt – IBW) Dosing Interval (Initial):
CrCl (ml / min) Interval
> 60 q 24 hours
59-40 q 36 hours
39-20 q 48 hours
CrCl = (140-age) x IBW / (72 x SrCr) [x 0.85 for female] Exclusion Criteria for Pulse-Dosing:
Ascites, > 20% burn, CF, ESRD, enterococcal endocarditis, hypermetabolic state, pregnancy, pediatric patients.
Lab Recommendations:
Day 1: baseline SrCr, RANDOM level 8 to 12 hrs post-infusion Day 3: SrCr
Day 5: SrCr and repeat RANDOM level 8 to 12 hrs post-infusion *Obtain random level if SrCr rises > 0.4 mg / dl above baseline. B. TIPS FOR ORDERING DRUG LEVELS
1. Always specify when the level is to be drawn (i.e. “trough level prior to 4th dose” or “random level in the
a.m.”). Orders for a drug level without specifying a time are generally drawn at 0400 regardless of the relationship to the time of the dose and are most often uninterpretable.
2. If you want the drug held until the level results are back, notify the nurse and write an order so stating. 3. Levels are primarily to help you assess therapeutic efficacy and/or toxicity. If at any time you suspect or
need to confirm efficacy or toxicity, order a level.
4. Patients with unstable renal function or volume status may require more frequent drug level monitoring. 5. Once a patient has stabilized on a drug-dosing regimen, you do not need to monitor drug levels as
frequently (i.e. every 5 to 7 days). For example, vanc 1 gm q 12h results in a trough of 7 mcg/ml after 3 doses, you do not need to recheck another trough level for 5 days unless the renal function changes. 6. When using digoxin to treat a. fib., monitoring the patient clinically (i.e. heart rate) is of more value than
a serum concentration. If the patient is stable (i.e. renal fxn and dosing), serum digoxin levels do not need to be obtained more than once a week. Do not obtain a digoxin level until at least 24 hours after loading digoxin.
7. If you add or discontinue a drug which interacts with the monitored drug, you may need to recheck the level once a new steady-state has been achieved (typically three doses) – i.e. cipro will increase
theophylline concentration by about 25%, therefore if you add cipro to a patient on theophylline, recheck the theophylline level in 24 hours.
8. Most drugs do not need to be dose adjusted until CrCl falls below 50 ml / min. CrCl can be estimated by using the Cockrauft-Gault equation:
female) for 0.85 ( 72 SrCr IBW x age) (140 CrCl
IBW = 50 kg = 2.3 kg (inches over 60) for male 45 kg + 2.3 kg (inches over 60 for female) (IBW = ideal body weight)
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9. You will often see a rise in serum drug levels (indicating less ability to clear the drug) before you will see a rise in serum creatinine. This should cue you that the patient’s renal function is declining and
appropriate measures should be made (including adjusting the dosage of other medications, removing potentially nephrotoxic agents, perhaps obtain a urine creatinine to confirm renal function).
10. Decrease in renal function is defined as increase in SrCr by 0.5 mg/dl or more or a rise in SrCr to 1.5 mg / dL or higher.
If you have any questions, call the pharmacy satellite (5-1518) or page Aimee LeClaire (413.1000). Figure 1
Table 1
E. Antimicrobial Therapeutic Drug Monitoring
1. Peak is defined as the maximum plasma drug concentration. A peak level should be drawn following the infusion of a monitorable drug.
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2. Trough is defined as the minimum plasma drug concentration. A trough level should be drawn immediately preceding a dose.
Conventionally dosed aminoglycosides: 1-2 mg/kg (x DBW*) IV every 8 – 12 hours
Concentration Gentamycin, tobramycin Amikacin
Peak (mcg/mL) 5 – 10 25 – 35
Trough (mcg/mL) 0.5 – 2 4 – 10
Obtain peak concentration ½-hour following completion of infusion of aminoglycoside. Obtain trough concentration ½-hour prior to dose.
Once Daily Aminoglycosides: 7 mg/kg (x DBW*) IV every 24 hours
Concentration Gentamycin, tobramycin Amikacin
Trough (mcg/mL) < 1 < 2
Obtain trough concentration ½-hour prior to dose.
Peak concentrations are not routinely measured with once daily aminoglycosides.
Random aminoglycoside levels may also be ordered following the infusion of a once daily aminoglycoside dosage.
A single random concentration may be drawn approximately 10 hours following the infusion of a once daily aminoglycoside dosage. The concentration and sampling time are plotted on the Hartford nomogram, which allows for assessment of drug clearance and any necessary dosage modifications. Alternatively, two random aminoglycoside concentrations may be drawn 4 hours and 12 hours
following the dose. The two random concentrations allow the pharmacist to calculate pharmacokinetic parameters, including elimination rate, half-life, volume of distribution, and extrapolated peaks and troughs.
*DBW = Dosing Body Weight = 0.4(ABW – IBW) + IBW, where ABW = Actual Body Weight and IBW = Ideal Body Weight. This is of particular importance for the morbidly obese.
Vancomycin
Concentration Vancomycin
Peak (mcg/mL) 20 – 40
Trough (mcg/mL) 5 – 20
Initial dosing and adjustments may be made via the Detroit Receiving Hospital Vancomycin
Nomogram,which was adopted for use at Shands at the University of Florida by the P&T Committee. When a patient has a change in renal status or altered renal function, a random vancomycin level
may be requested. Although officially labeled as a random concentration, the level is interpreted and applied as a trough concentration; that is, when a random concentration is obtained, typically re- dosing is appropriate when the vancomycin concentration is less than 15 – 20 mcg/mL.
A vancomycin trough concentration up to 15 to 20 mcg/mL may be necessary to ensure adequate tissue penetration depending on site of infection (i.e., lung and CNS).
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Section 11: Nutritional Support