As part of a series of blog posts surrounding World Patient Safety Day 2022's theme of 'Medication Safety', RCSEd Council Member and Surgeon (Associate Specialist) Majid Mukadam MBE and Organ Transplant Pharmacist Zahra Irshad discuss transplant immunosuppression in the perioperative period.
In more than one way, the perioperative period can be a challenging time for any patient, but more so for a transplant recipient. Everyone involved in their care needs to exercise extreme vigilance whilst dealing with this cohort of patients due to their long-term immunosuppression medications. Patient Safety Day provides a great opportunity to educate everyone who may come across these patients.
Solid organ transplant patients require careful management of their medications to prevent rejection, graft function deterioration and limit side effects of the drugs. Even a few incorrect, omitted, or delayed doses of immunosuppression can cause harm, often resulting in a hospital admission and deleterious clinical outcomes. These patients are generally managed by a team of expert clinicians, nurses, and pharmacists. Immunosuppression is commenced just before a patient goes for transplant surgery and is continued throughout their life span, with doses being gradually reduced but never stopped. Stable drug doses are achieved by monitoring plasma drug levels and organ function. A transplant recipient undergoes rigorous education to achieve a safe level of self-medication before they are discharged from hospital and their surveillance continues during their subsequent follow-up clinic visits.
However, this control may be lost or reduced when they require an elective or emergency admission to a non-transplant centre. Ideally for elective surgery, a plan will have been agreed by the Transplant team who will have advised on which medicines should be paused/dose adjusted, antibiotics to avoid, and what doses of steroids to use. If the transplant team cannot be contacted, it is important to get an accurate list of medication and doses, and often the patient will be the best person to ask.
The most common immunosuppressants used are calcenurin inhibitors (CNIs) - tacrolimus or ciclosporin, and anti-metabolites – azathioprine and mycophenolate mofetil (MMF) along with steroids. These should be continued throughout the perioperative period, avoiding any missed doses even when nil-by mouth. CNI trough levels should be measured, if possible, to guide dosage to maintain therapeutic levels. Suitably adjusted doses can be administered intravenously or sublingually if necessary. The CNIs are metabolised by the CYP3A4 enzymes, so are susceptible to numerous drug interactions, including macrolide antibiotics (eg erythromycin, clarithromycin) and azole antifungals (eg fluconazole, voriconazole). These should only be used with careful trough monitoring to prevent toxic plasma levels, though are best avoided if alternatives are available. In contrast, Sirolimus (often seen in combination with other immunosupressants) might need discontinuation before a major surgery to avoid delayed wound healing.
In case of renal function deterioration, leucopoenia, or active infection, the transplant team is best placed to advice on immunosuppression management. For patients on steroid therapy, stress dosing may be necessary during the perioperative period.
Ultimately, to keep the patient safe and prevent medication errors, a multidisciplinary approach is necessary, utilising patients, pharmacists, and the parent team as well as your own. Though when it gets to Friday night, and most of your colleagues have gone home, and you are looking at a transplant patient, checking the drug chart is a good place to start.