Generic name (brand name)
FDA approved for induction
Dose
Common adverse effects
Rabbit antithymocyte globulin (Thymoglobulin®)
No
1.5 mg/kg IV 3–5 doses. Infused over 6 h if central line or 12 h if peripheral line. Premedicate with acetaminophen, diphenhydramine, and steroids
Dose adjustments needed for low WBC counts and thrombocytopenia
Chills, rigors, fever, tachycardia rash, myelosuppression
Alemtuzumab (Campath-1H®)
No
20–30 mg IV × 1–2 doses
Flu-like symptoms, chills, rigor, fever, myelosuppression
Basiliximab (Simulect®)
Yes
20 mg IV × 2 doses (days 0 and 4)
None reported when compared with placebo
Postoperative Assessment
In order to assess the likelihood of delayed graft function information on the status of the donor is useful especially when dealing with a deceased donor transplant. The key data include information on causes/mechanisms of death, donor age, medical history, and cold/warm ischemia time. To monitor urine output a Foley catheter should be inserted; this will also help decompress the bladder. Understanding the patient’s hemodynamic status is important. To this end, adequate venous access should be established and an arterial line inserted. Use of a Swan-Ganz catheter is generally not required unless patients have severe left ventricular dysfunction, valvular abnormalities, or known pulmonary hypertension.
Depending on institutional policy, the postoperative care of the patient may take place in an ICU, “step-down” unit, or even the general floor. It is important that the nurses and the physicians taking care of these patients be well acquainted with the patient’s prior medical history. Table 23.2 lists common admit orders and protocols.
Table 23.2
Common admit orders and protocols
Admit orders: ICU, step-down, or surgical floor depending on institutional protocol |
Protective isolation |
Vital signs/monitoring: |
CVP monitoring every hour. Transduce with 0.9 % NS pressurized to 150 mmHg |
Central line care per clinical care protocol |
Central line infection prevention |
Pulse oximetry: every hour |
Strict intake and output every hour |
Vital signs: BP, HR, RR, peripheral pulses to be recorded post-procedure—on arrival, every 15 min for 1 h (or until stable)—followed by every 30 min for 2 h—followed by every hour as needed for 24 h—then unit routine postoperatively |
Activity |
Ambulate with assistance: three times daily. Start postoperative day 0 |
Out of bed to chair: three times daily |
Notify service: |
Name and pager of whom to contact |
Temp: ≥38.5 °C |
HR: ≥120 ≤ 60 bpm |
SBP: ≥180 ≤ 90 mmHg |
DBP: ≥110 ≤ 60 mmHg |
Pulse Ox: ≤92 % |
Urine output: ≤40 ml/h or ≥800 ml/h |
Nursing care: |
Incentive spirometry: 10 times every hour when awake |
Turn/cough/deep breathe |
Supplemental oxygen as needed to maintain oxygen saturation ≥92 % |
Maintain Foley catheter |
Weight daily: standing scale preferred |
DVT prophylaxis: apply sequential compression device (SCD), unless contraindicated |
: Heparin 5000 units SC tid. Avoid low molecular weight heparin |
Diet: NPO except for meds now |
Medications: |
PCA medications and nursing instructions; dilaudid and fentanyl PCA preferred |
Antiemetics:IV Ondansetron 4 mg q6h as needed for nausea and vomiting |
Antipruritic: Benadryl 25 mg PO or IV q6h as needed for itching |
Bowel regimen: Colace 100 mg po twice daily |
IV fluids |
Dextrose 2.5 %/0.45 % NaCl with 50 Meq of sodium bicarbonate 1000 ml: intravenous, at 100 ml/h |
Orders for 0.9 % NS and 0.45 % NS are also written for replacement protocol given below |
Replacement protocol: |
If urine output 1–100 ml/h—continue maintenance IV fluids |
If urine output 101–400 ml/h—replace urine output with 1:1 0.9 % NS |
If urine output 401–800 ml/h—replace urine output 1:1 or 0.5:1 with 0.45 % NS (surgeon preference) |
If urine output >800 ml/h—notify HO |
PCP prophylaxis: start postoperative day 1. Duration of prophylaxis varies institutionally |
Bactrim SS PO daily is the preferred agent |
If sulfa allergic and not G-6-PD deficient, select dapsone 100 mg PO daily |
If sulfa allergic and G6PD deficient select pentamidine 300 mg NEB every month |
Atovaquone 1500 mg po daily |
Candida prophylaxis |
Fluconazole (DIFLUCAN) tablet: 100 mg po daily: start postoperative day 1. Nystatin swish and swallow can also be used |
CMV prophylaxis as follows based on donor and recipient CMV status: |
Start postoperative day 1 (dose adjusted based on renal function) |
IF moderate to high risk (CMV D−/R+, D+/R+, D+/R−) |
Valganciclovir 450 mg PO daily |
IF low risk (CMV D−/R−) |
Acyclovir 400 mg PO every 12 h |
Steroid dosing: |
Methylprednisolone 200 mg IV postoperative day 1 |
Methylprednisolone 160 mg IV postoperative day 2 |
Methylprednisolone 120 mf IV postoperative day 3 |
Prednisone 80 mg PO postoperative day 4 |
Prednisone 40 PO postoperative day 5 |
Prednisone 20 mg PO postoperative day 6 and daily thereafter |
Some programs utilize rapid steroid taper (e.g., steroids off by end of first week) or steroid avoidance protocols. PO:IV conversion is 5:4 (prednisone to methylprednisolone) |
Antiproliferative agents: |
Mycophenolate mofetil 1000 mg po bid, mycophenolic acid 720 mg po twice daily. Oral to IV conversion is 1:1 |
Calcineurin inhibitor (typically tacrolimus): Monitor 12-h troughs. Goal range is typically 8–12 ng/ml for first 3 months post-transplant. Typical starting dose is 0.05 mg/kg PO every 12 h, but the starting dose may be altered based on the patient’s clinical status and/or drug interactions. Due to risk of toxicity, IV calcineurin inhibitors are generally avoided unless absolutely necessary. Sublingual administration of tacrolimus is an option if NPO |
Postoperative laboratory orders |
Complete blood count with platelets, renal function panel (includes magnesium, phosphorus, serum glucose) every 12 h for 24 h and then every morning unless clinically indicated |
Calcineurin inhibitor level (12 h trough) each morning |
Liver function tests if indicated, urine culture, and sensitivity |
Hemodynamic Status
Maintenance of stable perioperative hemodynamics is of utmost importance and to achieve this goal patients should be monitored carefully. Postoperatively recipients should be in slightly positive fluid balance along with higher blood pressures (we generally prefer SBP ≥ 150 mmHg and DBP ≥ 80 mmHg) to help maintain adequate perfusion of the newly transplanted organ. Replacement fluids should be given taking into account the patient’s urine output, insensible losses (averaging 500–1000 ml/day but varies depending on clinical condition), and volume status. However, care should be taken to gradually decrease the amount of replacement fluid while maintaining stable hemodynamics, as constant full-volume replacement only drives more diuresis. Most centers have their own protocols.
Common causes of postoperative hypotension include bleeding, effect of anesthetic medications, inadequate volume resuscitation, perioperative myocardial infarction with left ventricular dysfunction, aggressive ultrafiltration before transplantation, cytokine release syndrome, and sepsis or other causes of low systemic vascular resistance such as liver disease. If the patient is hypotensive isotonic fluids should be administered rapidly. If anemia is present packed red cells may be given to expand intravascular volume. If a central venous catheter is present the central venous pressures (CVP) (target 7–10 cm H2O) may help in guiding management of the patient’s volume status. Low blood pressures should be avoided to decrease the risk of acute tubular necrosis (ATN) and or risk of delayed graft function (DGF), which is defined as the need for dialysis within the first week of transplantation.
Persistent hypotension, abdominal pain, and a dropping hematocrit are all potential signs/symptoms of intra-abdominal bleeding. Most bleeding is self-limited, but any coagulopathy or thrombocytopenia if present should be reversed. In the event of concerns for a hematoma causing pressure on the ureteral anastomosis and vascular bundle or there is ongoing need for blood product and isotonic fluid infusions to maintain stable hemodynamics, the patient should be taken to the operating room, the bleeding contained, and hematoma evacuated.
Cytokine release syndrome is a rare condition that can be seen from antithymocyte globulin (due to its rabbit origin) generally during the first or second doses that is associated with fevers, chills, rash, myalgias, hypotension, and tachycardia. The treatment is to reduce the infusion rate and this usually resolves the problem. If the above signs and symptoms persist the infusion should be discontinued. Premedication with antihistamines, H2-blockers, and intravenous glucocorticoids can prevent or reduce the severity of symptoms. Since basiliximab and alemtuzumab are humanized monoclonal antibodies infusion reactions are not typically seen.
Aggressive pre-transplant ultrafiltration (usually performed with dialysis) can cause postoperative hypotension. Although there are no specific guidelines on how much pre-transplant volume removal is appropriate, it has been our practice to allow patients receiving pre-transplant dialysis/ultrafiltration to end the treatment 1.0–1.5 kg above their dry weight.
All patients who are candidates for a renal transplantation undergo stringent cardiovascular evaluation per institutional protocol prior to transplantation; hence perioperative acute myocardial infarction is uncommon. The incidence of in-hospital postoperative myocardial infarction (MI) after renal transplantation was found to be 1.6 % in a recent observational study [5]. In yet another older single-center retrospective study, the overall incidence of cardiac complications in the first 30 days post-transplant was noted to be 6.1 %. Cardiac complications in the latter study included MI (1.6 %), arrhythmia (2.7 %), angina (1.2 %), cardiac arrest (0.5 %), and congestive heart failure (0.1 %) [6]. EKGs should be done if there is a clinical suspicion of MI and cardiac enzymes including CK, CK-MB, and troponins should be sent. A cardiology consultation should be obtained to help with management if cardiac complications are suspected or diagnosed.
Hypertension should be only treated if the blood pressures are very high. We only treat systolic blood pressures greater than 170 and/or diastolic blood pressures greater than 100 after eliminating all potential factors such as pain and nausea. Commonly used intravenous antihypertensive medications include PRN doses of IV hydralazine 5–10 mg every hour as needed or labetalol 10–20 mg IVP over 2 min and can administer 40–80 mg at 10-min intervals with total maximum cumulative dose of 300 mg. Dihydropyridine calcium channel blockers (CCB) are a good oral choice and are our first-line oral antihypertensive medications. We avoid non-dihydropyridine CCBs such as verapamil and diltiazem since they decrease metabolism of tacrolimus and cyclosporine, and can cause nephrotoxicity if the calcineurin inhibitor levels are not closely monitored and adjusted. Awareness of patient’s pre-transplant antihypertensive medications is very important. Abrupt cessation of medications such as clonidine can cause rebound hypertension with very high blood pressures. We resume clonidine at smaller doses after transplant unless the patient is hypotensive; this is then weaned off over the next 2–4 weeks. Similar problems can be seen with patients who are on minoxidil and can be avoided by restarting the drug postoperatively and then gradually tapering it off. Wide fluctuations in blood pressure should raise the suspicion of autonomic dysfunction especially in patients with long-standing diabetes and their management can be quite challenging and is generally done in the outpatient setting.
Pain Control
It is our practice to use patient-controlled analgesia (PCA). Opiates remain the mainstay of analgesia and we prefer the use of fentanyl and hydromorphone. Morphine should be avoided in patients with CKD, ESRD, and recent transplantation due to the potential for significant accumulation of morphine-6-β glucuronide which has been reported to cause significant respiratory depression [7]. On the other hand fentanyl is metabolized in the liver to mostly norfentanyl and there is no evidence that any of its metabolites are active. Despite the risk of accumulation in renal failure and potentially respiratory depression, fentanyl has had a good short-term safety profile. Hydromorphone is another drug that can be considered for analgesia in renal failure patients. Although 3-glucuronide metabolites can accumulate and are neuro-excitatory, it has been used safely in renal failure patients [8].